Computational genetic neuroanatomy of the developing mouse brain: dimensionality reduction, visualization, and clustering

PubMed Central

2013-01-01

Background The structured organization of cells in the brain plays a key role in its functional efficiency. This delicate organization is the consequence of unique molecular identity of each cell gradually established by precise spatiotemporal gene expression control during development. Currently, studies on the molecular-structural association are beginning to reveal how the spatiotemporal gene expression patterns are related to cellular differentiation and structural development. Results In this article, we aim at a global, data-driven study of the relationship between gene expressions and neuroanatomy in the developing mouse brain. To enable visual explorations of the high-dimensional data, we map the in situ hybridization gene expression data to a two-dimensional space by preserving both the global and the local structures. Our results show that the developing brain anatomy is largely preserved in the reduced gene expression space. To provide a quantitative analysis, we cluster the reduced data into groups and measure the consistency with neuroanatomy at multiple levels. Our results show that the clusters in the low-dimensional space are more consistent with neuroanatomy than those in the original space. Conclusions Gene expression patterns and developing brain anatomy are closely related. Dimensionality reduction and visual exploration facilitate the study of this relationship. PMID:23845024

A lifelong exposure to a Western-style diet, but not aging, alters global DNA methylation in mouse colon

PubMed Central

Tammen, Stephanie A; Liu, Zhenhua; Friso, Simonetta

2015-01-01

BACKGROUND/OBJECTIVES Previous studies have indicated that when compared to young mice, old mice have lower global DNA methylation and higher p16 promoter methylation in colonic mucosa, which is a common finding in colon cancer. It is also known that a Western-style diet (WSD) high in fat and calories, and low in calcium, vitamin D, fiber, methionine and choline (based on the AIN 76A diet) is tumorigenic in colons of mice. Because DNA methylation is modifiable by diet, we investigate whether a WSD disrupts DNA methylation patterns, creating a tumorigenic environment. SUBJECTVIES/METHODS We investigated the effects of a WSD and aging on global and p16 promoter DNA methylation in the colon. Two month old male C57BL/6 mice were fed either a WSD or a control diet (AIN76A) for 6, 12 or 17 months. Global DNA methylation, p16 promoter methylation and p16 expression were determined by LC/MS, methyl-specific PCR and real time RT-PCR, respectively. RESULTS The WSD group demonstrated significantly decreased global DNA methylation compared with the control at 17 months (4.05 vs 4.31%, P = 0.019). While both diets did not change global DNA methylation over time, mice fed the WSD had lower global methylation relative to controls when comparing all animals (4.13 vs 4.30%, P = 0.0005). There was an increase in p16 promoter methylation from 6 to 17 months in both diet groups (P < 0.05) but no differences were observed between diet groups. Expression of p16 increased with age in both control and WSD groups. CONCLUSIONS In this model a WSD reduces global DNA methylation, whereas aging itself has no affect. Although the epigenetic effect of aging was not strong enough to alter global DNA methylation, changes in promoter-specific methylation and gene expression occurred with aging regardless of diet, demonstrating the complexity of epigenetic patterns. PMID:26244073

Attention switching during scene perception: how goals influence the time course of eye movements across advertisements.

PubMed

Wedel, Michel; Pieters, Rik; Liechty, John

2008-06-01

Eye movements across advertisements express a temporal pattern of bursts of respectively relatively short and long saccades, and this pattern is systematically influenced by activated scene perception goals. This was revealed by a continuous-time hidden Markov model applied to eye movements of 220 participants exposed to 17 ads under a free-viewing condition, and a scene-learning goal (ad memorization), a scene-evaluation goal (ad appreciation), a target-learning goal (product learning), or a target-evaluation goal (product evaluation). The model reflects how attention switches between two states--local and global--expressed in saccades of shorter and longer amplitude on a spatial grid with 48 cells overlaid on the ads. During the 5- to 6-s duration of self-controlled exposure to ads in the magazine context, attention predominantly started in the local state and ended in the global state, and rapidly switched about 5 times between states. The duration of the local attention state was much longer than the duration of the global state. Goals affected the frequency of switching between attention states and the duration of the local, but not of the global, state. (c) 2008 APA, all rights reserved

Optimal consistency in microRNA expression analysis using reference-gene-based normalization.

PubMed

Wang, Xi; Gardiner, Erin J; Cairns, Murray J

2015-05-01

Normalization of high-throughput molecular expression profiles secures differential expression analysis between samples of different phenotypes or biological conditions, and facilitates comparison between experimental batches. While the same general principles apply to microRNA (miRNA) normalization, there is mounting evidence that global shifts in their expression patterns occur in specific circumstances, which pose a challenge for normalizing miRNA expression data. As an alternative to global normalization, which has the propensity to flatten large trends, normalization against constitutively expressed reference genes presents an advantage through their relative independence. Here we investigated the performance of reference-gene-based (RGB) normalization for differential miRNA expression analysis of microarray expression data, and compared the results with other normalization methods, including: quantile, variance stabilization, robust spline, simple scaling, rank invariant, and Loess regression. The comparative analyses were executed using miRNA expression in tissue samples derived from subjects with schizophrenia and non-psychiatric controls. We proposed a consistency criterion for evaluating methods by examining the overlapping of differentially expressed miRNAs detected using different partitions of the whole data. Based on this criterion, we found that RGB normalization generally outperformed global normalization methods. Thus we recommend the application of RGB normalization for miRNA expression data sets, and believe that this will yield a more consistent and useful readout of differentially expressed miRNAs, particularly in biological conditions characterized by large shifts in miRNA expression.

Response of heat shock protein genes of the oriental fruit moth under diapause and thermal stress reveals multiple patterns dependent on the nature of stress exposure.

PubMed

Zhang, Bo; Peng, Yu; Zheng, Jincheng; Liang, Lina; Hoffmann, Ary A; Ma, Chun-Sen

2016-07-01

Heat shock protein gene (Hsp) families are thought to be important in thermal adaptation, but their expression patterns under various thermal stresses have still been poorly characterized outside of model systems. We have therefore characterized Hsp genes and their stress responses in the oriental fruit moth (OFM), Grapholita molesta, a widespread global orchard pest, and compared patterns of expression in this species to that of other insects. Genes from four Hsp families showed variable expression levels among tissues and developmental stages. Members of the Hsp40, 70, and 90 families were highly expressed under short exposures to heat and cold. Expression of Hsp40, 70, and Hsc70 family members increased in OFM undergoing diapause, while Hsp90 was downregulated. We found that there was strong sequence conservation of members of large Hsp families (Hsp40, Hsp60, Hsp70, Hsc70) across taxa, but this was not always matched by conservation of expression patterns. When the large Hsps as well as small Hsps from OFM were compared under acute and ramping heat stress, two groups of sHsps expression patterns were apparent, depending on whether expression increased or decreased immediately after stress exposure. These results highlight potential differences in conservation of function as opposed to sequence in this gene family and also point to Hsp genes potentially useful as bioindicators of diapause and thermal stress in OFM.

Global gene expression of Prochlorococcus ecotypes in response to changes in nitrogen availability

PubMed Central

Tolonen, Andrew C; Aach, John; Lindell, Debbie; Johnson, Zackary I; Rector, Trent; Steen, Robert; Church, George M; Chisholm, Sallie W

2006-01-01

Nitrogen (N) often limits biological productivity in the oceanic gyres where Prochlorococcus is the most abundant photosynthetic organism. The Prochlorococcus community is composed of strains, such as MED4 and MIT9313, that have different N utilization capabilities and that belong to ecotypes with different depth distributions. An interstrain comparison of how Prochlorococcus responds to changes in ambient nitrogen is thus central to understanding its ecology. We quantified changes in MED4 and MIT9313 global mRNA expression, chlorophyll fluorescence, and photosystem II photochemical efficiency (Fv/Fm) along a time series of increasing N starvation. In addition, the global expression of both strains growing in ammonium-replete medium was compared to expression during growth on alternative N sources. There were interstrain similarities in N regulation such as the activation of a putative NtcA regulon during N stress. There were also important differences between the strains such as in the expression patterns of carbon metabolism genes, suggesting that the two strains integrate N and C metabolism in fundamentally different ways. PMID:17016519

Quantitative RT-PCR Comparison of the Urea and Nitric Oxide Cycle Gene Transcripts in Adult Human Tissues

PubMed Central

Neill, Meaghan Anne; Aschner, Judy; Barr, Frederick; Summar, Marshall L.

2009-01-01

The urea cycle and nitric oxide cycle play significant roles in complex biochemical and physiologic reactions. These cycles have distinct biochemical goals including the clearance of waste nitrogen; the production of the intermediates ornithine, citrulline, and arginine for the urea cycle; and the production of nitric oxide for the nitric oxide pathway. Despite their disparate functions, the two pathways share two enzymes, argininosuccinic acid synthase and argininosuccinic acid lyase, and a transporter, citrin. Studying the gene expression of these enzymes is paramount in understanding these complex biochemical pathways. Here, we examine the expression of genes involved in the urea cycle and the nitric oxide cycle in a panel of eleven different tissue samples obtained from individual adults without known inborn errors of metabolism. In this study, the pattern of co-expressed enzymes provides a global view of the metabolic activity of the urea and nitric oxide cycles in human tissues. Our results show that these transcripts are differentially expressed in different tissues. The pattern of co-expressed enzymes provides a global view of the metabolic activity of the urea and nitric oxide cycles in human tissues. Using the co-expression profiles, we discovered that the combination of expression of enzyme transcripts as detected in our study, might serve to fulfill specific physiologic function(s) in tissue including urea production/nitrogen removal, arginine/citrulline production, nitric oxide production, and ornithine production. Our study reveals the importance of studying not only the expression profile of an enzyme of interest, but also studying the expression profiles of the other enzymes involved in a particular pathway so as to better understand the context of expression. The tissue patterns we observed highlight the variety of important functions they conduct and provide insight into many of the clinical observations from their disruption. PMID:19345634

An ancient rule for constructing dodecagonal quasiperiodic patterns

NASA Astrophysics Data System (ADS)

Ajlouni, Rima

2017-02-01

The discovery of complex dodecagonal patterns in historical Islamic architecture is generating a renewed interest into understanding the mathematical principles of traditional Islamic geometry. By employing a compass and a straightedge, ancient craftsmen utilized consistent design principles that allowed for diverse geometric expressions to be realized throughout the ancient world. Derived from these principles, a global multi-level structural model is proposed that provides a general guiding principle for constructing a wide variety of infinite dodecagon-based quasiperiodic patterns.

Alterations of Global DNA Methylation and DNA Methyltransferase Expression in T and B Lymphocytes from Patients with Newly Diagnosed Autoimmune Thyroid Diseases After Treatment: A Follow-Up Study.

PubMed

Guo, Qingling; Wu, Dan; Yu, Huixin; Bao, Jiandong; Peng, Shiqiao; Shan, Zhongyan; Guan, Haixia; Teng, Weiping

2018-03-01

Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid diseases and to observe methylation changes after treatment for these conditions. A cross-sectional study was conducted, including the following patients: 51 with newly diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD patients treated with radioiodine or antithyroid drugs and 28 AIT patients treated with L-thyroxine were followed for three months. Serum free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using electrochemiluminescent immunoassays. CD3 + T and CD19 + B cells were separated by flow cytometry for total DNA and RNA extraction. Global DNA methylation levels were determined by absorptiometry using a methylation quantification kit. DNA methyltransferase (DNMT) expression levels were detected by real-time polymerase chain reaction. Hypomethylation and down-regulated DNMT1 expression in T and B lymphocytes were observed in the newly diagnosed GD patients. Neither the AIT patients nor the positive thyroid autoantibodies patients exhibited differences in their global DNA methylation status or DNMT mRNA levels compared with healthy controls. Antithyroid drugs restored global methylation and DNMT1 expression in both T and B lymphocytes, whereas radioiodine therapy affected only T cells. L-thyroxine replacement did not alter the methylation or DNMT expression levels in lymphocytes. The global methylation levels of B cells were negatively correlated with the serum thyroid peroxidase antibodies in patients with autoimmune thyroid diseases. Hyperthyroid patients with newly diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B lymphocytes. The results provide the first demonstration that antithyroid drugs or radioiodine treatment restore global DNA methylation and DNMT1 expression with concurrent relief of hyperthyroidism.

In Vitro Assays for Mouse Müller Cell Phenotyping Through microRNA Profiling in the Damaged Retina.

PubMed

Reyes-Aguirre, Luis I; Quintero, Heberto; Estrada-Leyva, Brenda; Lamas, Mónica

2018-01-01

microRNA profiling has identified cell-specific expression patterns that could represent molecular signatures triggering the acquisition of a specific phenotype; in other words, of cellular identity and its associated function. Several groups have hypothesized that retinal cell phenotyping could be achieved through the determination of the global pattern of miRNA expression across specific cell types in the adult retina. This is especially relevant for Müller glia in the context of retinal damage, as these cells undergo dramatic changes of gene expression in response to injury, that render them susceptible to acquire a progenitor-like phenotype and be a source of new neurons.We describe a method that combines an experimental protocol for excitotoxic-induced retinal damage through N-methyl-D-aspartate subretinal injection with magnetic-activated cell sorting (MACS) of Müller cells and RNA isolation for microRNA profiling. Comparison of microRNA patterns of expression should allow Müller cell phenotyping under different experimental conditions.

Phytoplankton-bacterial interactions mediate micronutrient colimitation at the coastal Antarctic sea ice edge.

PubMed

Bertrand, Erin M; McCrow, John P; Moustafa, Ahmed; Zheng, Hong; McQuaid, Jeffrey B; Delmont, Tom O; Post, Anton F; Sipler, Rachel E; Spackeen, Jenna L; Xu, Kai; Bronk, Deborah A; Hutchins, David A; Allen, Andrew E

2015-08-11

Southern Ocean primary productivity plays a key role in global ocean biogeochemistry and climate. At the Southern Ocean sea ice edge in coastal McMurdo Sound, we observed simultaneous cobalamin and iron limitation of surface water phytoplankton communities in late Austral summer. Cobalamin is produced only by bacteria and archaea, suggesting phytoplankton-bacterial interactions must play a role in this limitation. To characterize these interactions and investigate the molecular basis of multiple nutrient limitation, we examined transitions in global gene expression over short time scales, induced by shifts in micronutrient availability. Diatoms, the dominant primary producers, exhibited transcriptional patterns indicative of co-occurring iron and cobalamin deprivation. The major contributor to cobalamin biosynthesis gene expression was a gammaproteobacterial population, Oceanospirillaceae ASP10-02a. This group also contributed significantly to metagenomic cobalamin biosynthesis gene abundance throughout Southern Ocean surface waters. Oceanospirillaceae ASP10-02a displayed elevated expression of organic matter acquisition and cell surface attachment-related genes, consistent with a mutualistic relationship in which they are dependent on phytoplankton growth to fuel cobalamin production. Separate bacterial groups, including Methylophaga, appeared to rely on phytoplankton for carbon and energy sources, but displayed gene expression patterns consistent with iron and cobalamin deprivation. This suggests they also compete with phytoplankton and are important cobalamin consumers. Expression patterns of siderophore- related genes offer evidence for bacterial influences on iron availability as well. The nature and degree of this episodic colimitation appear to be mediated by a series of phytoplankton-bacterial interactions in both positive and negative feedback loops.

Phytoplankton–bacterial interactions mediate micronutrient colimitation at the coastal Antarctic sea ice edge

PubMed Central

Bertrand, Erin M.; McCrow, John P.; Moustafa, Ahmed; Zheng, Hong; McQuaid, Jeffrey B.; Delmont, Tom O.; Post, Anton F.; Sipler, Rachel E.; Spackeen, Jenna L.; Xu, Kai; Bronk, Deborah A.; Hutchins, David A.; Allen, Andrew E.

2015-01-01

Southern Ocean primary productivity plays a key role in global ocean biogeochemistry and climate. At the Southern Ocean sea ice edge in coastal McMurdo Sound, we observed simultaneous cobalamin and iron limitation of surface water phytoplankton communities in late Austral summer. Cobalamin is produced only by bacteria and archaea, suggesting phytoplankton–bacterial interactions must play a role in this limitation. To characterize these interactions and investigate the molecular basis of multiple nutrient limitation, we examined transitions in global gene expression over short time scales, induced by shifts in micronutrient availability. Diatoms, the dominant primary producers, exhibited transcriptional patterns indicative of co-occurring iron and cobalamin deprivation. The major contributor to cobalamin biosynthesis gene expression was a gammaproteobacterial population, Oceanospirillaceae ASP10-02a. This group also contributed significantly to metagenomic cobalamin biosynthesis gene abundance throughout Southern Ocean surface waters. Oceanospirillaceae ASP10-02a displayed elevated expression of organic matter acquisition and cell surface attachment-related genes, consistent with a mutualistic relationship in which they are dependent on phytoplankton growth to fuel cobalamin production. Separate bacterial groups, including Methylophaga, appeared to rely on phytoplankton for carbon and energy sources, but displayed gene expression patterns consistent with iron and cobalamin deprivation. This suggests they also compete with phytoplankton and are important cobalamin consumers. Expression patterns of siderophore- related genes offer evidence for bacterial influences on iron availability as well. The nature and degree of this episodic colimitation appear to be mediated by a series of phytoplankton–bacterial interactions in both positive and negative feedback loops. PMID:26221022

Customized Molecular Phenotyping by Quantitative Gene Expression and Pattern Recognition Analysis

PubMed Central

Akilesh, Shreeram; Shaffer, Daniel J.; Roopenian, Derry

2003-01-01

Description of the molecular phenotypes of pathobiological processes in vivo is a pressing need in genomic biology. We have implemented a high-throughput real-time PCR strategy to establish quantitative expression profiles of a customized set of target genes. It enables rapid, reproducible data acquisition from limited quantities of RNA, permitting serial sampling of mouse blood during disease progression. We developed an easy to use statistical algorithm—Global Pattern Recognition—to readily identify genes whose expression has changed significantly from healthy baseline profiles. This approach provides unique molecular signatures for rheumatoid arthritis, systemic lupus erythematosus, and graft versus host disease, and can also be applied to defining the molecular phenotype of a variety of other normal and pathological processes. PMID:12840047

A high resolution atlas of gene expression in the domestic sheep (Ovis aries)

PubMed Central

Farquhar, Iseabail L.; Young, Rachel; Lefevre, Lucas; Pridans, Clare; Tsang, Hiu G.; Afrasiabi, Cyrus; Watson, Mick; Whitelaw, C. Bruce; Freeman, Tom C.; Archibald, Alan L.; Hume, David A.

2017-01-01

Sheep are a key source of meat, milk and fibre for the global livestock sector, and an important biomedical model. Global analysis of gene expression across multiple tissues has aided genome annotation and supported functional annotation of mammalian genes. We present a large-scale RNA-Seq dataset representing all the major organ systems from adult sheep and from several juvenile, neonatal and prenatal developmental time points. The Ovis aries reference genome (Oar v3.1) includes 27,504 genes (20,921 protein coding), of which 25,350 (19,921 protein coding) had detectable expression in at least one tissue in the sheep gene expression atlas dataset. Network-based cluster analysis of this dataset grouped genes according to their expression pattern. The principle of ‘guilt by association’ was used to infer the function of uncharacterised genes from their co-expression with genes of known function. We describe the overall transcriptional signatures present in the sheep gene expression atlas and assign those signatures, where possible, to specific cell populations or pathways. The findings are related to innate immunity by focusing on clusters with an immune signature, and to the advantages of cross-breeding by examining the patterns of genes exhibiting the greatest expression differences between purebred and crossbred animals. This high-resolution gene expression atlas for sheep is, to our knowledge, the largest transcriptomic dataset from any livestock species to date. It provides a resource to improve the annotation of the current reference genome for sheep, presenting a model transcriptome for ruminants and insight into gene, cell and tissue function at multiple developmental stages. PMID:28915238

A high resolution atlas of gene expression in the domestic sheep (Ovis aries).

PubMed

Clark, Emily L; Bush, Stephen J; McCulloch, Mary E B; Farquhar, Iseabail L; Young, Rachel; Lefevre, Lucas; Pridans, Clare; Tsang, Hiu G; Wu, Chunlei; Afrasiabi, Cyrus; Watson, Mick; Whitelaw, C Bruce; Freeman, Tom C; Summers, Kim M; Archibald, Alan L; Hume, David A

2017-09-01

Sheep are a key source of meat, milk and fibre for the global livestock sector, and an important biomedical model. Global analysis of gene expression across multiple tissues has aided genome annotation and supported functional annotation of mammalian genes. We present a large-scale RNA-Seq dataset representing all the major organ systems from adult sheep and from several juvenile, neonatal and prenatal developmental time points. The Ovis aries reference genome (Oar v3.1) includes 27,504 genes (20,921 protein coding), of which 25,350 (19,921 protein coding) had detectable expression in at least one tissue in the sheep gene expression atlas dataset. Network-based cluster analysis of this dataset grouped genes according to their expression pattern. The principle of 'guilt by association' was used to infer the function of uncharacterised genes from their co-expression with genes of known function. We describe the overall transcriptional signatures present in the sheep gene expression atlas and assign those signatures, where possible, to specific cell populations or pathways. The findings are related to innate immunity by focusing on clusters with an immune signature, and to the advantages of cross-breeding by examining the patterns of genes exhibiting the greatest expression differences between purebred and crossbred animals. This high-resolution gene expression atlas for sheep is, to our knowledge, the largest transcriptomic dataset from any livestock species to date. It provides a resource to improve the annotation of the current reference genome for sheep, presenting a model transcriptome for ruminants and insight into gene, cell and tissue function at multiple developmental stages.

Global analysis of DNA methylation in young (J1) and senescent (J2) Gossypium hirsutum L. cotyledons by MeDIP-Seq

PubMed Central

Dou, Lingling; Jia, Xiaoyun; Wei, Hengling; Fan, Shuli; Wang, Hantao; Guo, Yaning; Duan, Shan; Pang, Chaoyou; Yu, Shuxun

2017-01-01

DNA methylation is an important epigenetic modification regulating gene expression, genomic imprinting, transposon silencing and chromatin structure in plants and plays an important role in leaf senescence. However, the DNA methylation pattern during Gossypium hirsutum L. cotyledon senescence is poorly understood. In this study, global DNA methylation patterns were compared between two cotyledon development stages, young (J1) and senescence (J2), using methylated DNA immunoprecipitation (MeDIP-Seq). Methylated cytosine occurred mostly in repeat elements, especially LTR/Gypsy in both J1 and J2. When comparing J1 against J2, there were 1222 down-methylated genes and 623 up-methylated genes. Methylated genes were significantly enriched in carbohydrate metabolism, biosynthesis of other secondary metabolites and amino acid metabolism pathways. The global DNA methylation level decreased from J1 to J2, especially in gene promoters, transcriptional termination regions and regions around CpG islands. We further investigated the expression patterns of 9 DNA methyltransferase-associated genes and 2 DNA demethyltransferase-associated genes from young to senescent cotyledons, which were down-regulated during cotyledon development. In this paper, we first reported that senescent cotton cotyledons exhibited lower DNA methylation levels, primarily due to decreased DNA methyltransferase activity and which also play important role in regulating secondary metabolite process. PMID:28715427

Tissue-specific NETs alter genome organization and regulation even in a heterologous system.

PubMed

de Las Heras, Jose I; Zuleger, Nikolaj; Batrakou, Dzmitry G; Czapiewski, Rafal; Kerr, Alastair R W; Schirmer, Eric C

2017-01-02

Different cell types exhibit distinct patterns of 3D genome organization that correlate with changes in gene expression in tissue and differentiation systems. Several tissue-specific nuclear envelope transmembrane proteins (NETs) have been found to influence the spatial positioning of genes and chromosomes that normally occurs during tissue differentiation. Here we study 3 such NETs: NET29, NET39, and NET47, which are expressed preferentially in fat, muscle and liver, respectively. We found that even when exogenously expressed in a heterologous system they can specify particular genome organization patterns and alter gene expression. Each NET affected largely different subsets of genes. Notably, the liver-specific NET47 upregulated many genes in HT1080 fibroblast cells that are normally upregulated in hepatogenesis, showing that tissue-specific NETs can favor expression patterns associated with the tissue where the NET is normally expressed. Similarly, global profiling of peripheral chromatin after exogenous expression of these NETs using lamin B1 DamID revealed that each NET affected the nuclear positioning of distinct sets of genomic regions with a significant tissue-specific component. Thus NET influences on genome organization can contribute to gene expression changes associated with differentiation even in the absence of other factors and overt cellular differentiation changes.

Whole-Genome Analysis of the SHORT-ROOT Developmental Pathway in Arabidopsis

PubMed Central

Busch, Wolfgang; Cui, Hongchang; Wang, Jean Y; Blilou, Ikram; Hassan, Hala; Nakajima, Keiji; Matsumoto, Noritaka; Lohmann, Jan U; Scheres, Ben

2006-01-01

Stem cell function during organogenesis is a key issue in developmental biology. The transcription factor SHORT-ROOT (SHR) is a critical component in a developmental pathway regulating both the specification of the root stem cell niche and the differentiation potential of a subset of stem cells in the Arabidopsis root. To obtain a comprehensive view of the SHR pathway, we used a statistical method called meta-analysis to combine the results of several microarray experiments measuring the changes in global expression profiles after modulating SHR activity. Meta-analysis was first used to identify the direct targets of SHR by combining results from an inducible form of SHR driven by its endogenous promoter, ectopic expression, followed by cell sorting and comparisons of mutant to wild-type roots. Eight putative direct targets of SHR were identified, all with expression patterns encompassing subsets of the native SHR expression domain. Further evidence for direct regulation by SHR came from binding of SHR in vivo to the promoter regions of four of the eight putative targets. A new role for SHR in the vascular cylinder was predicted from the expression pattern of several direct targets and confirmed with independent markers. The meta-analysis approach was then used to perform a global survey of the SHR indirect targets. Our analysis suggests that the SHR pathway regulates root development not only through a large transcription regulatory network but also through hormonal pathways and signaling pathways using receptor-like kinases. Taken together, our results not only identify the first nodes in the SHR pathway and a new function for SHR in the development of the vascular tissue but also reveal the global architecture of this developmental pathway. PMID:16640459

Genome-wide expression and methylation profiling in the aged rodent brain due to early-life Pb exposure and its relevance to aging.

PubMed

Dosunmu, Remi; Alashwal, Hany; Zawia, Nasser H

2012-06-01

In this study, we assessed global gene expression patterns in adolescent mice exposed to lead (Pb) as infants and their aged siblings to identify reprogrammed genes. Global expression on postnatal day 20 and 700 was analyzed and genes that were down- and up-regulated (≥2 fold) were identified, clustered and analyzed for their relationship to DNA methylation. About 150 genes were differentially expressed in old age. In normal aging, we observed an up-regulation of genes related to the immune response, metal-binding, metabolism and transcription/transduction coupling. Prior exposure to Pb revealed a repression in these genes suggesting that disturbances in developmental stages of the brain compromise the ability to defend against age-related stressors, thus promoting the neurodegenerative process. Overexpression and repression of genes corresponded with their DNA methylation profile. Published by Elsevier Ireland Ltd.

An improved Pearson's correlation proximity-based hierarchical clustering for mining biological association between genes.

PubMed

Booma, P M; Prabhakaran, S; Dhanalakshmi, R

2014-01-01

Microarray gene expression datasets has concerned great awareness among molecular biologist, statisticians, and computer scientists. Data mining that extracts the hidden and usual information from datasets fails to identify the most significant biological associations between genes. A search made with heuristic for standard biological process measures only the gene expression level, threshold, and response time. Heuristic search identifies and mines the best biological solution, but the association process was not efficiently addressed. To monitor higher rate of expression levels between genes, a hierarchical clustering model was proposed, where the biological association between genes is measured simultaneously using proximity measure of improved Pearson's correlation (PCPHC). Additionally, the Seed Augment algorithm adopts average linkage methods on rows and columns in order to expand a seed PCPHC model into a maximal global PCPHC (GL-PCPHC) model and to identify association between the clusters. Moreover, a GL-PCPHC applies pattern growing method to mine the PCPHC patterns. Compared to existing gene expression analysis, the PCPHC model achieves better performance. Experimental evaluations are conducted for GL-PCPHC model with standard benchmark gene expression datasets extracted from UCI repository and GenBank database in terms of execution time, size of pattern, significance level, biological association efficiency, and pattern quality.

An Improved Pearson's Correlation Proximity-Based Hierarchical Clustering for Mining Biological Association between Genes

PubMed Central

Booma, P. M.; Prabhakaran, S.; Dhanalakshmi, R.

2014-01-01

Microarray gene expression datasets has concerned great awareness among molecular biologist, statisticians, and computer scientists. Data mining that extracts the hidden and usual information from datasets fails to identify the most significant biological associations between genes. A search made with heuristic for standard biological process measures only the gene expression level, threshold, and response time. Heuristic search identifies and mines the best biological solution, but the association process was not efficiently addressed. To monitor higher rate of expression levels between genes, a hierarchical clustering model was proposed, where the biological association between genes is measured simultaneously using proximity measure of improved Pearson's correlation (PCPHC). Additionally, the Seed Augment algorithm adopts average linkage methods on rows and columns in order to expand a seed PCPHC model into a maximal global PCPHC (GL-PCPHC) model and to identify association between the clusters. Moreover, a GL-PCPHC applies pattern growing method to mine the PCPHC patterns. Compared to existing gene expression analysis, the PCPHC model achieves better performance. Experimental evaluations are conducted for GL-PCPHC model with standard benchmark gene expression datasets extracted from UCI repository and GenBank database in terms of execution time, size of pattern, significance level, biological association efficiency, and pattern quality. PMID:25136661

Coordinated transcriptional regulation patterns associated with infertility phenotypes in men

PubMed Central

Ellis, Peter J I; Furlong, Robert A; Conner, Sarah J; Kirkman‐Brown, Jackson; Afnan, Masoud; Barratt, Christopher; Griffin, Darren K; Affara, Nabeel A

2007-01-01

Introduction Microarray gene‐expression profiling is a powerful tool for global analysis of the transcriptional consequences of disease phenotypes. Understanding the genetic correlates of particular pathological states is important for more accurate diagnosis and screening of patients, and thus for suggesting appropriate avenues of treatment. As yet, there has been little research describing gene‐expression profiling of infertile and subfertile men, and thus the underlying transcriptional events involved in loss of spermatogenesis remain unclear. Here we present the results of an initial screen of 33 patients with differing spermatogenic phenotypes. Methods Oligonucleotide array expression profiling was performed on testis biopsies for 33 patients presenting for testicular sperm extraction. Significantly regulated genes were selected using a mixed model analysis of variance. Principle components analysis and hierarchical clustering were used to interpret the resulting dataset with reference to the patient history, clinical findings and histological composition of the biopsies. Results Striking patterns of coordinated gene expression were found. The most significant contains multiple germ cell‐specific genes and corresponds to the degree of successful spermatogenesis in each patient, whereas a second pattern corresponds to inflammatory activity within the testis. Smaller‐scale patterns were also observed, relating to unique features of the individual biopsies. PMID:17496197

Recrudescence Mechanisms and Gene Expression Profile of the Reproductive Tracts from Chickens during the Molting Period

PubMed Central

Ahn, Suzie E.; Lim, Chul-Hong; Lee, Jin-Young; Bae, Seung-Min; Kim, Jinyoung; Bazer, Fuller W.; Song, Gwonhwa

2013-01-01

The reproductive system of chickens undergoes dynamic morphological and functional tissue remodeling during the molting period. The present study identified global gene expression profiles following oviductal tissue regression and regeneration in laying hens in which molting was induced by feeding high levels of zinc in the diet. During the molting and recrudescence processes, progressive morphological and physiological changes included regression and re-growth of reproductive organs and fluctuations in concentrations of testosterone, progesterone, estradiol and corticosterone in blood. The cDNA microarray analysis of oviductal tissues revealed the biological significance of gene expression-based modulation in oviductal tissue during its remodeling. Based on the gene expression profiles, expression patterns of selected genes such as, TF, ANGPTL3, p20K, PTN, AvBD11 and SERPINB3 exhibited similar patterns in expression with gradual decreases during regression of the oviduct and sequential increases during resurrection of the functional oviduct. Also, miR-1689* inhibited expression of Sp1, while miR-17-3p, miR-22* and miR-1764 inhibited expression of STAT1. Similarly, chicken miR-1562 and miR-138 reduced the expression of ANGPTL3 and p20K, respectively. These results suggest that these differentially regulated genes are closely correlated with the molecular mechanism(s) for development and tissue remodeling of the avian female reproductive tract, and that miRNA-mediated regulation of key genes likely contributes to remodeling of the avian reproductive tract by controlling expression of those genes post-transcriptionally. The discovered global gene profiles provide new molecular candidates responsible for regulating morphological and functional recrudescence of the avian reproductive tract, and provide novel insights into understanding the remodeling process at the genomic and epigenomic levels. PMID:24098561

De novo Transcriptome Assembly of Chinese Kale and Global Expression Analysis of Genes Involved in Glucosinolate Metabolism in Multiple Tissues

PubMed Central

Wu, Shuanghua; Lei, Jianjun; Chen, Guoju; Chen, Hancai; Cao, Bihao; Chen, Changming

2017-01-01

Chinese kale, a vegetable of the cruciferous family, is a popular crop in southern China and Southeast Asia due to its high glucosinolate content and nutritional qualities. However, there is little research on the molecular genetics and genes involved in glucosinolate metabolism and its regulation in Chinese kale. In this study, we sequenced and characterized the transcriptomes and expression profiles of genes expressed in 11 tissues of Chinese kale. A total of 216 million 150-bp clean reads were generated using RNA-sequencing technology. From the sequences, 98,180 unigenes were assembled for the whole plant, and 49,582~98,423 unigenes were assembled for each tissue. Blast analysis indicated that a total of 80,688 (82.18%) unigenes exhibited similarity to known proteins. The functional annotation and classification tools used in this study suggested that genes principally expressed in Chinese kale, were mostly involved in fundamental processes, such as cellular and molecular functions, the signal transduction, and biosynthesis of secondary metabolites. The expression levels of all unigenes were analyzed in various tissues of Chinese kale. A large number of candidate genes involved in glucosinolate metabolism and its regulation were identified, and the expression patterns of these genes were analyzed. We found that most of the genes involved in glucosinolate biosynthesis were highly expressed in the root, petiole, and in senescent leaves. The expression patterns of ten glucosinolate biosynthetic genes from RNA-seq were validated by quantitative RT-PCR in different tissues. These results provided an initial and global overview of Chinese kale gene functions and expression activities in different tissues. PMID:28228764

Global Expression Profiling in Atopic Eczema Reveals Reciprocal Expression of Inflammatory and Lipid Genes

PubMed Central

Sääf, Annika M.; Tengvall-Linder, Maria; Chang, Howard Y.; Adler, Adam S.; Wahlgren, Carl-Fredrik; Scheynius, Annika; Nordenskjöld, Magnus; Bradley, Maria

2008-01-01

Background Atopic eczema (AE) is a common chronic inflammatory skin disorder. In order to dissect the genetic background several linkage and genetic association studies have been performed. Yet very little is known about specific genes involved in this complex skin disease, and the underlying molecular mechanisms are not fully understood. Methodology/Findings We used human DNA microarrays to identify a molecular picture of the programmed responses of the human genome to AE. The transcriptional program was analyzed in skin biopsy samples from lesional and patch-tested skin from AE patients sensitized to Malassezia sympodialis (M. sympodialis), and corresponding biopsies from healthy individuals. The most notable feature of the global gene-expression pattern observed in AE skin was a reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. The overall transcriptional response in M. sympodialis patch-tested AE skin was similar to the gene-expression signature identified in lesional AE skin. In the constellation of genes differentially expressed in AE skin compared to healthy control skin, we have identified several potential susceptibility genes that may play a critical role in the pathological condition of AE. Many of these genes, including genes with a role in immune responses, lipid homeostasis, and epidermal differentiation, are localized on chromosomal regions previously linked to AE. Conclusions/Significance Through genome-wide expression profiling, we were able to discover a distinct reciprocal expression pattern of induced inflammatory genes and repressed lipid metabolism genes in skin from AE patients. We found a significant enrichment of differentially expressed genes in AE with cytobands associated to the disease, and furthermore new chromosomal regions were found that could potentially guide future region-specific linkage mapping in AE. The full data set is available at http://microarray-pubs.stanford.edu/eczema. PMID:19107207

Global Gene Expression Change Induced by Major Thoracoabdominal Surgery.

PubMed

Allen, Casey J; Griswold, Anthony J; Schulman, Carl I; Sleeman, Danny; Levi, Joe U; Livingstone, Alan S; Proctor, Kenneth G

2017-12-01

To test the hypothesis that major thoracoabdominal surgery induces gene expression changes associated with adverse outcomes. Widely different traumatic injuries evoke surprisingly similar gene expression profiles, but there is limited information on whether the iatrogenic injury caused by major surgery is associated with similar patterns. With informed consent, blood samples were obtained from 50 patients before and after open transhiatal esophagectomy or pancreaticoduodenectomy. Twelve cases with complicated recoveries (death, infection, venous thromboembolism) were matched with 12 cases with uneventful recoveries. Global gene expression was assayed using human microarray chips. A 2-fold change with a corrected P < 0.05 was considered differentially expressed. In these 24 patients, 522 genes were differentially expressed after surgery; 248 (48%) were upregulated (innate immunity and inflammation) and 274 (52%) were downregulated [adaptive immunity (antigen presentation, T-cell function)]. Hierarchical clustering of the profile reliably predicted pre- and postoperative status. The within-patient change was 3.08 ± 0.91-fold. There was no measurable association with age, malignancy, procedure, surgery length, operative blood loss, or transfusion requirements, but was positively associated with postoperative infection (3.81 ± 0.97 vs 2.79 ± 0.73; P = 0.009) and hospital length of stay (r = 0.583, P = 0.003). Venous thromboembolism and mortality each occurred in one patient, thus no associations were possible. Major surgery induces a quantifiable pattern of gene expression change that is associated with adverse outcome. This could reflect early impaired adaptive immunity and suggests potential therapeutic targets to improve postoperative recovery.

Voices from Ethiopia: A Global Connection.

ERIC Educational Resources Information Center

Honeyghan, Glasceta

2001-01-01

Presents a model for motivating seventh- and tenth-grade Ethiopian students to write poetry about their personal feelings and experiences. Describes four strategies for the poetry workshop: acrostic, lune, counting pattern, and one that explores feelings and personal emotion. Notes that all exercises encouraged children to express themselves on…

Detection of changes in gene regulatory patterns, elicited by perturbations of the Hsp90 molecular chaperone complex, by visualizing multiple experiments with an animation

PubMed Central

2011-01-01

Background To make sense out of gene expression profiles, such analyses must be pushed beyond the mere listing of affected genes. For example, if a group of genes persistently display similar changes in expression levels under particular experimental conditions, and the proteins encoded by these genes interact and function in the same cellular compartments, this could be taken as very strong indicators for co-regulated protein complexes. One of the key requirements is having appropriate tools to detect such regulatory patterns. Results We have analyzed the global adaptations in gene expression patterns in the budding yeast when the Hsp90 molecular chaperone complex is perturbed either pharmacologically or genetically. We integrated these results with publicly accessible expression, protein-protein interaction and intracellular localization data. But most importantly, all experimental conditions were simultaneously and dynamically visualized with an animation. This critically facilitated the detection of patterns of gene expression changes that suggested underlying regulatory networks that a standard analysis by pairwise comparison and clustering could not have revealed. Conclusions The results of the animation-assisted detection of changes in gene regulatory patterns make predictions about the potential roles of Hsp90 and its co-chaperone p23 in regulating whole sets of genes. The simultaneous dynamic visualization of microarray experiments, represented in networks built by integrating one's own experimental with publicly accessible data, represents a powerful discovery tool that allows the generation of new interpretations and hypotheses. PMID:21672238

Gene Expression Dynamics Inspector (GEDI): for integrative analysis of expression profiles

NASA Technical Reports Server (NTRS)

Eichler, Gabriel S.; Huang, Sui; Ingber, Donald E.

2003-01-01

Genome-wide expression profiles contain global patterns that evade visual detection in current gene clustering analysis. Here, a Gene Expression Dynamics Inspector (GEDI) is described that uses self-organizing maps to translate high-dimensional expression profiles of time courses or sample classes into animated, coherent and robust mosaics images. GEDI facilitates identification of interesting patterns of molecular activity simultaneously across gene, time and sample space without prior assumption of any structure in the data, and then permits the user to retrieve genes of interest. Important changes in genome-wide activities may be quickly identified based on 'Gestalt' recognition and hence, GEDI may be especially useful for non-specialist end users, such as physicians. AVAILABILITY: GEDI v1.0 is written in Matlab, and binary Matlab.dll files which require Matlab to run can be downloaded for free by academic institutions at http://www.chip.org/ge/gedihome.html Supplementary information: http://www.chip.org/ge/gedihome.html.

Comparative analysis of growth-phase-dependent gene expression in virulent and avirulent Streptococcus pneumoniae using a high-density DNA microarray.

PubMed

Ko, Kwan Soo; Park, Sulhee; Oh, Won Sup; Suh, Ji-Yoeun; Oh, Taejeong; Ahn, Sungwhan; Chun, Jongsik; Song, Jae-Hoon

2006-02-28

The global pattern of growth-dependent gene expres-sion in Streptococcus pneumoniae strains was evalu-ated using a high-density DNA microarray. Total RNAs obtained from an avirulent S. pneumoniae strain R6 and a virulent strain AMC96-6 were used to compare the expression patterns at seven time points (2.5, 3.5, 4.5, 5.5, 6.0, 6.5, and 8.0 h). The expression profile of strain R6 changed between log and station-ary growth (the Log-Stat switch). There were clear differences between the growth-dependent gene ex-pression profiles of the virulent and avirulent pneumo-coccal strains in 367 of 1,112 genes. Transcripts of genes associated with bacterial competence and capsular polysaccharide formation, as well as clpP and cbpA, were higher in the virulent strain. Our data suggest that late log or early stationary phase may be the most virulent phase of S. pneumoniae.

Early In Vitro Differentiation of Mouse Definitive Endoderm Is Not Correlated with Progressive Maturation of Nuclear DNA Methylation Patterns

PubMed Central

Tajbakhsh, Jian; Gertych, Arkadiusz; Fagg, W. Samuel; Hatada, Seigo; Fair, Jeffrey H.

2011-01-01

The genome organization in pluripotent cells undergoing the first steps of differentiation is highly relevant to the reprogramming process in differentiation. Considering this fact, chromatin texture patterns that identify cells at the very early stage of lineage commitment could serve as valuable tools in the selection of optimal cell phenotypes for regenerative medicine applications. Here we report on the first-time use of high-resolution three-dimensional fluorescence imaging and comprehensive topological cell-by-cell analyses with a novel image-cytometrical approach towards the identification of in situ global nuclear DNA methylation patterns in early endodermal differentiation of mouse ES cells (up to day 6), and the correlations of these patterns with a set of putative markers for pluripotency and endodermal commitment, and the epithelial and mesenchymal character of cells. Utilizing this in vitro cell system as a model for assessing the relationship between differentiation and nuclear DNA methylation patterns, we found that differentiating cell populations display an increasing number of cells with a gain in DNA methylation load: first within their euchromatin, then extending into heterochromatic areas of the nucleus, which also results in significant changes of methylcytosine/global DNA codistribution patterns. We were also able to co-visualize and quantify the concomitant stochastic marker expression on a per-cell basis, for which we did not measure any correlation to methylcytosine loads or distribution patterns. We observe that the progression of global DNA methylation is not correlated with the standard transcription factors associated with endodermal development. Further studies are needed to determine whether the progression of global methylation could represent a useful signature of cellular differentiation. This concept of tracking epigenetic progression may prove useful in the selection of cell phenotypes for future regenerative medicine applications. PMID:21779341

Self-Organizing Global Gene Expression Regulated through Criticality: Mechanism of the Cell-Fate Change

PubMed Central

Tsuchiya, Masa; Giuliani, Alessandro; Hashimoto, Midori; Erenpreisa, Jekaterina; Yoshikawa, Kenichi

2016-01-01

Background A fundamental issue in bioscience is to understand the mechanism that underlies the dynamic control of genome-wide expression through the complex temporal-spatial self-organization of the genome to regulate the change in cell fate. We address this issue by elucidating a physically motivated mechanism of self-organization. Principal Findings Building upon transcriptome experimental data for seven distinct cell fates, including early embryonic development, we demonstrate that self-organized criticality (SOC) plays an essential role in the dynamic control of global gene expression regulation at both the population and single-cell levels. The novel findings are as follows: i) Mechanism of cell-fate changes: A sandpile-type critical transition self-organizes overall expression into a few transcription response domains (critical states). A cell-fate change occurs by means of a dissipative pulse-like global perturbation in self-organization through the erasure of initial-state critical behaviors (criticality). Most notably, the reprogramming of early embryo cells destroys the zygote SOC control to initiate self-organization in the new embryonal genome, which passes through a stochastic overall expression pattern. ii) Mechanism of perturbation of SOC controls: Global perturbations in self-organization involve the temporal regulation of critical states. Quantitative evaluation of this perturbation in terminal cell fates reveals that dynamic interactions between critical states determine the critical-state coherent regulation. The occurrence of a temporal change in criticality perturbs this between-states interaction, which directly affects the entire genomic system. Surprisingly, a sub-critical state, corresponding to an ensemble of genes that shows only marginal changes in expression and consequently are considered to be devoid of any interest, plays an essential role in generating a global perturbation in self-organization directed toward the cell-fate change. Conclusion and Significance ‘Whole-genome’ regulation of gene expression through self-regulatory SOC control complements gene-by-gene fine tuning and represents a still largely unexplored non-equilibrium statistical mechanism that is responsible for the massive reprogramming of genome expression. PMID:27997556

Local Context Finder (LCF) reveals multidimensional relationships among mRNA expression profiles of Arabidopsis responding to pathogen infection

PubMed Central

Katagiri, Fumiaki; Glazebrook, Jane

2003-01-01

A major task in computational analysis of mRNA expression profiles is definition of relationships among profiles on the basis of similarities among them. This is generally achieved by pattern recognition in the distribution of data points representing each profile in a high-dimensional space. Some drawbacks of commonly used pattern recognition algorithms stem from their use of a globally linear space and/or limited degrees of freedom. A pattern recognition method called Local Context Finder (LCF) is described here. LCF uses nonlinear dimensionality reduction for pattern recognition. Then it builds a network of profiles based on the nonlinear dimensionality reduction results. LCF was used to analyze mRNA expression profiles of the plant host Arabidopsis interacting with the bacterial pathogen Pseudomonas syringae. In one case, LCF revealed two dimensions essential to explain the effects of the NahG transgene and the ndr1 mutation on resistant and susceptible responses. In another case, plant mutants deficient in responses to pathogen infection were classified on the basis of LCF analysis of their profiles. The classification by LCF was consistent with the results of biological characterization of the mutants. Thus, LCF is a powerful method for extracting information from expression profile data. PMID:12960373

Common patterns and disease-related signatures in tuberculosis and sarcoidosis.

PubMed

Maertzdorf, Jeroen; Weiner, January; Mollenkopf, Hans-Joachim; Bauer, Torsten; Prasse, Antje; Müller-Quernheim, Joachim; Kaufmann, Stefan H E

2012-05-15

In light of the marked global health impact of tuberculosis (TB), strong focus has been on identifying biosignatures. Gene expression profiles in blood cells identified so far are indicative of a persistent activation of the immune system and chronic inflammatory pathology in active TB. Definition of a biosignature with unique specificity for TB demands that identified profiles can differentiate diseases with similar pathology, like sarcoidosis (SARC). Here, we present a detailed comparison between pulmonary TB and SARC, including whole-blood gene expression profiling, microRNA expression, and multiplex serum analytes. Our analysis reveals that previously disclosed gene expression signatures in TB show highly similar patterns in SARC, with a common up-regulation of proinflammatory pathways and IFN signaling and close similarity to TB-related signatures. microRNA expression also presented a highly similar pattern in both diseases, whereas cytokines in the serum of TB patients revealed a slightly elevated proinflammatory pattern compared with SARC and controls. Our results indicate several differences in expression between the two diseases, with increased metabolic activity and significantly higher antimicrobial defense responses in TB. However, matrix metallopeptidase 14 was identified as the most distinctive marker of SARC. Described communalities as well as unique signatures in blood profiles of two distinct inflammatory pulmonary diseases not only have considerable implications for the design of TB biosignatures and future diagnosis, but they also provide insights into biological processes underlying chronic inflammatory disease entities of different etiology.

Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription

PubMed Central

2011-01-01

Background Artemisinin resistance in Plasmodium falciparum malaria has emerged in Western Cambodia. This is a major threat to global plans to control and eliminate malaria as the artemisinins are a key component of antimalarial treatment throughout the world. To identify key features associated with the delayed parasite clearance phenotype, we employed DNA microarrays to profile the physiological gene expression pattern of the resistant isolates. Results In the ring and trophozoite stages, we observed reduced expression of many basic metabolic and cellular pathways which suggests a slower growth and maturation of these parasites during the first half of the asexual intraerythrocytic developmental cycle (IDC). In the schizont stage, there is an increased expression of essentially all functionalities associated with protein metabolism which indicates the prolonged and thus increased capacity of protein synthesis during the second half of the resistant parasite IDC. This modulation of the P. falciparum intraerythrocytic transcriptome may result from differential expression of regulatory proteins such as transcription factors or chromatin remodeling associated proteins. In addition, there is a unique and uniform copy number variation pattern in the Cambodian parasites which may represent an underlying genetic background that contributes to the resistance phenotype. Conclusions The decreased metabolic activities in the ring stages are consistent with previous suggestions of higher resilience of the early developmental stages to artemisinin. Moreover, the increased capacity of protein synthesis and protein turnover in the schizont stage may contribute to artemisinin resistance by counteracting the protein damage caused by the oxidative stress and/or protein alkylation effect of this drug. This study reports the first global transcriptional survey of artemisinin resistant parasites and provides insight to the complexities of the molecular basis of pathogens with drug resistance phenotypes in vivo. PMID:21810278

Final Report - Epigenetics of low dose radiation effects in an animal model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kovalchuk, Olga

This project sought mechanistic understanding of the epigenetic response of tissues as well as the consequences of those responses, when induced by low dose irradiation in a well-established model system (mouse). Based on solid and extensive preliminary data we investigated the molecular epigenetic mechanisms of in vivo radiation responses, particularly – effects of low, occupationally relevant radiation exposures on the genome stability and adaptive response in mammalian tissues and organisms. We accumulated evidence that low dose irradiation altered epigenetic profiles and impacted radiation target organs of the exposed animals. The main long-term goal was to dissect the epigenetic basis ofmore » induction of the low dose radiation-induced genome instability and adaptive response and the specific fundamental roles of epigenetic changes (i.e. DNA methylation, histone modifications and miRNAs) in their generation. We hypothesized that changes in global and regional DNA methylation, global histone modifications and regulatory microRNAs played pivotal roles in the generation and maintenance low-dose radiation-induced genome instability and adaptive response. We predicted that epigenetic changes influenced the levels of genetic rearrangements (transposone reactivation). We hypothesized that epigenetic responses from low dose irradiation were dependent on exposure regimes, and would be greatest when organisms are exposed in a protracted/fractionated manner: fractionated exposures > acute exposures. We anticipated that the epigenetic responses were correlated with the gene expression levels. Our immediate objectives were: • To investigate the exact nature of the global and locus-specific DNA methylation changes in the LDR exposed cells and tissues and dissect their roles in adaptive response • To investigate the roles of histone modifications in the low dose radiation effects and adaptive response • To dissect the roles of regulatory microRNAs and their targets in low dose radiation effects and adaptive response • To correlate the levels of epigenetic changes with genetic rearrangement levels and gene expression patterns. In sum, we determined the precise global and locus-specific DNA methylation patterns in the LDR-exposed cells and tissues of mice, and to correlated DNA methylation changes with the gene expression patterns and manifestations of genome instability. We also determined the alterations of global histone modification pattern in the LDR exposed tissues. Additionally, we established the nature of microRNAome changes in the LDR exposed tissue. In this study we for the first time found that LDR exposure caused profound tissue-specific epigenetic changes in the exposed tissues. We established that LDR exposure affect methylation of repetitive elements in the murine genome, causes changes in histone methylation, acetylation and phosphorylation. Importantly, we found that LDR causes profound and persistent effects on small RNA profiles and gene expression, and that miRNAs are excellent biomarkers of LDR exposure. Furthermore, we extended our analysis and studied LDR effects in rat tissues and human tissues and cell lines. There we also analyzed LDR-induced gene expression, DNA methylation and miRNA changes. Our datasets laid foundation for several new research projects aimed to understand molecular underpinnings of low dose radiation responses, and biological repercussions of low dose radiation effects and radiation carcinogenesis.« less

Metaproteomics reveals differential modes of metabolic coupling among ubiquitous oxygen minimum zone microbes

PubMed Central

Hawley, Alyse K.; Brewer, Heather M.; Norbeck, Angela D.; Paša-Tolić, Ljiljana; Hallam, Steven J.

2014-01-01

Marine oxygen minimum zones (OMZs) are intrinsic water column features arising from respiratory oxygen demand during organic matter degradation in stratified waters. Currently OMZs are expanding due to global climate change with resulting feedback on marine ecosystem function. Here we use metaproteomics to chart spatial and temporal patterns of gene expression along defined redox gradients in a seasonally stratified fjord to better understand microbial community responses to OMZ expansion. The expression of metabolic pathway components for nitrification, anaerobic ammonium oxidation (anammox), denitrification, and inorganic carbon fixation were differentially expressed across the redoxcline and covaried with distribution patterns of ubiquitous OMZ microbes including Thaumarchaeota, Nitrospina, Nitrospira, Planctomycetes, and SUP05/ARCTIC96BD-19 Gammaproteobacteria. Nitrification and inorganic carbon fixation pathways affiliated with Thaumarchaeota dominated dysoxic waters, and denitrification, sulfur oxidation, and inorganic carbon fixation pathways affiliated with the SUP05 group of nitrate-reducing sulfur oxidizers dominated suboxic and anoxic waters. Nitrifier nitrite oxidation and anammox pathways affiliated with Nirospina, Nitrospira, and Planctomycetes, respectively, also exhibited redox partitioning between dysoxic and suboxic waters. The numerical abundance of SUP05 proteins mediating inorganic carbon fixation under anoxic conditions suggests that SUP05 will become increasingly important in global ocean carbon and nutrient cycling as OMZs expand. PMID:25053816

Metaproteomics reveals differential modes of metabolic coupling among ubiquitous oxygen minimum zone microbes.

PubMed

Hawley, Alyse K; Brewer, Heather M; Norbeck, Angela D; Paša-Tolić, Ljiljana; Hallam, Steven J

2014-08-05

Marine oxygen minimum zones (OMZs) are intrinsic water column features arising from respiratory oxygen demand during organic matter degradation in stratified waters. Currently OMZs are expanding due to global climate change with resulting feedback on marine ecosystem function. Here we use metaproteomics to chart spatial and temporal patterns of gene expression along defined redox gradients in a seasonally stratified fjord to better understand microbial community responses to OMZ expansion. The expression of metabolic pathway components for nitrification, anaerobic ammonium oxidation (anammox), denitrification, and inorganic carbon fixation were differentially expressed across the redoxcline and covaried with distribution patterns of ubiquitous OMZ microbes including Thaumarchaeota, Nitrospina, Nitrospira, Planctomycetes, and SUP05/ARCTIC96BD-19 Gammaproteobacteria. Nitrification and inorganic carbon fixation pathways affiliated with Thaumarchaeota dominated dysoxic waters, and denitrification, sulfur oxidation, and inorganic carbon fixation pathways affiliated with the SUP05 group of nitrate-reducing sulfur oxidizers dominated suboxic and anoxic waters. Nitrifier nitrite oxidation and anammox pathways affiliated with Nirospina, Nitrospira, and Planctomycetes, respectively, also exhibited redox partitioning between dysoxic and suboxic waters. The numerical abundance of SUP05 proteins mediating inorganic carbon fixation under anoxic conditions suggests that SUP05 will become increasingly important in global ocean carbon and nutrient cycling as OMZs expand.

Ocean salinities reveal strong global water cycle intensification during 1950 to 2000.

PubMed

Durack, Paul J; Wijffels, Susan E; Matear, Richard J

2012-04-27

Fundamental thermodynamics and climate models suggest that dry regions will become drier and wet regions will become wetter in response to warming. Efforts to detect this long-term response in sparse surface observations of rainfall and evaporation remain ambiguous. We show that ocean salinity patterns express an identifiable fingerprint of an intensifying water cycle. Our 50-year observed global surface salinity changes, combined with changes from global climate models, present robust evidence of an intensified global water cycle at a rate of 8 ± 5% per degree of surface warming. This rate is double the response projected by current-generation climate models and suggests that a substantial (16 to 24%) intensification of the global water cycle will occur in a future 2° to 3° warmer world.

A multi-Poisson dynamic mixture model to cluster developmental patterns of gene expression by RNA-seq.

PubMed

Ye, Meixia; Wang, Zhong; Wang, Yaqun; Wu, Rongling

2015-03-01

Dynamic changes of gene expression reflect an intrinsic mechanism of how an organism responds to developmental and environmental signals. With the increasing availability of expression data across a time-space scale by RNA-seq, the classification of genes as per their biological function using RNA-seq data has become one of the most significant challenges in contemporary biology. Here we develop a clustering mixture model to discover distinct groups of genes expressed during a period of organ development. By integrating the density function of multivariate Poisson distribution, the model accommodates the discrete property of read counts characteristic of RNA-seq data. The temporal dependence of gene expression is modeled by the first-order autoregressive process. The model is implemented with the Expectation-Maximization algorithm and model selection to determine the optimal number of gene clusters and obtain the estimates of Poisson parameters that describe the pattern of time-dependent expression of genes from each cluster. The model has been demonstrated by analyzing a real data from an experiment aimed to link the pattern of gene expression to catkin development in white poplar. The usefulness of the model has been validated through computer simulation. The model provides a valuable tool for clustering RNA-seq data, facilitating our global view of expression dynamics and understanding of gene regulation mechanisms. © The Author 2014. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Transcriptional maturation of the mouse auditory forebrain.

PubMed

Hackett, Troy A; Guo, Yan; Clause, Amanda; Hackett, Nicholas J; Garbett, Krassimira; Zhang, Pan; Polley, Daniel B; Mirnics, Karoly

2015-08-14

The maturation of the brain involves the coordinated expression of thousands of genes, proteins and regulatory elements over time. In sensory pathways, gene expression profiles are modified by age and sensory experience in a manner that differs between brain regions and cell types. In the auditory system of altricial animals, neuronal activity increases markedly after the opening of the ear canals, initiating events that culminate in the maturation of auditory circuitry in the brain. This window provides a unique opportunity to study how gene expression patterns are modified by the onset of sensory experience through maturity. As a tool for capturing these features, next-generation sequencing of total RNA (RNAseq) has tremendous utility, because the entire transcriptome can be screened to index expression of any gene. To date, whole transcriptome profiles have not been generated for any central auditory structure in any species at any age. In the present study, RNAseq was used to profile two regions of the mouse auditory forebrain (A1, primary auditory cortex; MG, medial geniculate) at key stages of postnatal development (P7, P14, P21, adult) before and after the onset of hearing (~P12). Hierarchical clustering, differential expression, and functional geneset enrichment analyses (GSEA) were used to profile the expression patterns of all genes. Selected genesets related to neurotransmission, developmental plasticity, critical periods and brain structure were highlighted. An accessible repository of the entire dataset was also constructed that permits extraction and screening of all data from the global through single-gene levels. To our knowledge, this is the first whole transcriptome sequencing study of the forebrain of any mammalian sensory system. Although the data are most relevant for the auditory system, they are generally applicable to forebrain structures in the visual and somatosensory systems, as well. The main findings were: (1) Global gene expression patterns were tightly clustered by postnatal age and brain region; (2) comparing A1 and MG, the total numbers of differentially expressed genes were comparable from P7 to P21, then dropped to nearly half by adulthood; (3) comparing successive age groups, the greatest numbers of differentially expressed genes were found between P7 and P14 in both regions, followed by a steady decline in numbers with age; (4) maturational trajectories in expression levels varied at the single gene level (increasing, decreasing, static, other); (5) between regions, the profiles of single genes were often asymmetric; (6) GSEA revealed that genesets related to neural activity and plasticity were typically upregulated from P7 to adult, while those related to structure tended to be downregulated; (7) GSEA and pathways analysis of selected functional networks were not predictive of expression patterns in the auditory forebrain for all genes, reflecting regional specificity at the single gene level. Gene expression in the auditory forebrain during postnatal development is in constant flux and becomes increasingly stable with age. Maturational changes are evident at the global through single gene levels. Transcriptome profiles in A1 and MG are distinct at all ages, and differ from other brain regions. The database generated by this study provides a rich foundation for the identification of novel developmental biomarkers, functional gene pathways, and targeted studies of postnatal maturation in the auditory forebrain.

Global profiling of alternative RNA splicing events provides insights into molecular differences between various types of hepatocellular carcinoma.

PubMed

Tremblay, Marie-Pier; Armero, Victoria E S; Allaire, Andréa; Boudreault, Simon; Martenon-Brodeur, Camille; Durand, Mathieu; Lapointe, Elvy; Thibault, Philippe; Tremblay-Létourneau, Maude; Perreault, Jean-Pierre; Scott, Michelle S; Bisaillon, Martin

2016-08-26

Dysregulations in alternative splicing (AS) patterns have been associated with many human diseases including cancer. In the present study, alterations to the global RNA splicing landscape of cellular genes were investigated in a large-scale screen from 377 liver tissue samples using high-throughput RNA sequencing data. Our study identifies modifications in the AS patterns of transcripts encoded by more than 2500 genes such as tumor suppressor genes, transcription factors, and kinases. These findings provide insights into the molecular differences between various types of hepatocellular carcinoma (HCC). Our analysis allowed the identification of 761 unique transcripts for which AS is misregulated in HBV-associated HCC, while 68 are unique to HCV-associated HCC, 54 to HBV&HCV-associated HCC, and 299 to virus-free HCC. Moreover, we demonstrate that the expression pattern of the RNA splicing factor hnRNPC in HCC tissues significantly correlates with patient survival. We also show that the expression of the HBx protein from HBV leads to modifications in the AS profiles of cellular genes. Finally, using RNA interference and a reverse transcription-PCR screening platform, we examined the implications of cellular proteins involved in the splicing of transcripts involved in apoptosis and demonstrate the potential contribution of these proteins in AS control. This study provides the first comprehensive portrait of global changes in the RNA splicing signatures that occur in hepatocellular carcinoma. Moreover, these data allowed us to identify unique signatures of genes for which AS is misregulated in the different types of HCC.

Sex bias and dosage compensation in the zebra finch versus chicken genomes: General and specialized patterns among birds

PubMed Central

Itoh, Yuichiro; Replogle, Kirstin; Kim, Yong-Hwan; Wade, Juli; Clayton, David F.; Arnold, Arthur P.

2010-01-01

We compared global patterns of gene expression between two bird species, the chicken and zebra finch, with regard to sex bias of autosomal versus Z chromosome genes, dosage compensation, and evolution of sex bias. Both species appear to lack a Z chromosome–wide mechanism of dosage compensation, because both have a similar pattern of significantly higher expression of Z genes in males relative to females. Unlike the chicken Z chromosome, which has female-specific expression of the noncoding RNA MHM (male hypermethylated) and acetylation of histone 4 lysine 16 (H4K16) near MHM, the zebra finch Z chromosome appears to lack the MHM sequence and acetylation of H4K16. The zebra finch also does not show the reduced male-to-female (M:F) ratio of gene expression near MHM similar to that found in the chicken. Although the M:F ratios of Z chromosome gene expression are similar across tissues and ages within each species, they differ between the two species. Z genes showing the greatest species difference in M:F ratio were concentrated near the MHM region of the chicken Z chromosome. This study shows that the zebra finch differs from the chicken because it lacks a specialized region of greater dosage compensation along the Z chromosome, and shows other differences in sex bias. These patterns suggest that different avian taxa may have evolved specific compensatory mechanisms. PMID:20357053

Retinoic acid influences anteroposterior positioning of epidermal sensory neurons and their gene expression in a developing chordate (amphioxus)

PubMed Central

Schubert, Michael; Holland, Nicholas D.; Escriva, Hector; Holland, Linda Z.; Laudet, Vincent

2004-01-01

In developing chordates, retinoic acid (RA) signaling patterns the rostrocaudal body axis globally and affects gene expression locally in some differentiating cell populations. Here we focus on development of epidermal sensory neurons in an invertebrate chordate (amphioxus) to determine how RA signaling influences their rostrocaudal distribution and gene expression (for AmphiCoe, a neural precursor gene; for amphioxus islet and AmphiERR, two neural differentiation genes; and for AmphiHox1, -3, -4, and -6). Treatments with RA or an RA antagonist (BMS009) shift the distribution of developing epidermal neurons anteriorly or posteriorly, respectively. These treatments also affect gene expression patterns in the epidermal neurons, suggesting that RA levels may influence specification of neuronal subtypes. Although colinear expression of Hox genes is well known for the amphioxus central nervous system, we find an unexpected comparable colinearity for AmphiHox1, -3, -4, and -6 in the developing epidermis; moreover, RA levels affect the anteroposterior extent of these Hox expression domains, suggesting that RA signaling controls a colinear Hox code for anteroposterior patterning of the amphioxus epidermis. Thus, in amphioxus, the developing peripheral nervous system appears to be structured by mechanisms parallel to those that structure the central nervous system. One can speculate that, during evolution, an ancestral deuterostome that structured its panepidermal nervous system with an RA-influenced Hox code gave rise to chordates in which this patterning mechanism persisted within the epidermal elements of the peripheral nervous system and was transferred to the neuroectoderm as the central nervous system condensed dorsally. PMID:15226493

Time course of gene expression during mouse skeletal muscle hypertrophy

PubMed Central

Lee, Jonah D.; England, Jonathan H.; Esser, Karyn A.; McCarthy, John J.

2013-01-01

The purpose of this study was to perform a comprehensive transcriptome analysis during skeletal muscle hypertrophy to identify signaling pathways that are operative throughout the hypertrophic response. Global gene expression patterns were determined from microarray results on days 1, 3, 5, 7, 10, and 14 during plantaris muscle hypertrophy induced by synergist ablation in adult mice. Principal component analysis and the number of differentially expressed genes (cutoffs ≥2-fold increase or ≥50% decrease compared with control muscle) revealed three gene expression patterns during overload-induced hypertrophy: early (1 day), intermediate (3, 5, and 7 days), and late (10 and 14 days) patterns. Based on the robust changes in total RNA content and in the number of differentially expressed genes, we focused our attention on the intermediate gene expression pattern. Ingenuity Pathway Analysis revealed a downregulation of genes encoding components of the branched-chain amino acid degradation pathway during hypertrophy. Among these genes, five were predicted by Ingenuity Pathway Analysis or previously shown to be regulated by the transcription factor Kruppel-like factor-15, which was also downregulated during hypertrophy. Moreover, the integrin-linked kinase signaling pathway was activated during hypertrophy, and the downregulation of muscle-specific micro-RNA-1 correlated with the upregulation of five predicted targets associated with the integrin-linked kinase pathway. In conclusion, we identified two novel pathways that may be involved in muscle hypertrophy, as well as two upstream regulators (Kruppel-like factor-15 and micro-RNA-1) that provide targets for future studies investigating the importance of these pathways in muscle hypertrophy. PMID:23869057

Time course of gene expression during mouse skeletal muscle hypertrophy.

PubMed

Chaillou, Thomas; Lee, Jonah D; England, Jonathan H; Esser, Karyn A; McCarthy, John J

2013-10-01

The purpose of this study was to perform a comprehensive transcriptome analysis during skeletal muscle hypertrophy to identify signaling pathways that are operative throughout the hypertrophic response. Global gene expression patterns were determined from microarray results on days 1, 3, 5, 7, 10, and 14 during plantaris muscle hypertrophy induced by synergist ablation in adult mice. Principal component analysis and the number of differentially expressed genes (cutoffs ≥2-fold increase or ≥50% decrease compared with control muscle) revealed three gene expression patterns during overload-induced hypertrophy: early (1 day), intermediate (3, 5, and 7 days), and late (10 and 14 days) patterns. Based on the robust changes in total RNA content and in the number of differentially expressed genes, we focused our attention on the intermediate gene expression pattern. Ingenuity Pathway Analysis revealed a downregulation of genes encoding components of the branched-chain amino acid degradation pathway during hypertrophy. Among these genes, five were predicted by Ingenuity Pathway Analysis or previously shown to be regulated by the transcription factor Kruppel-like factor-15, which was also downregulated during hypertrophy. Moreover, the integrin-linked kinase signaling pathway was activated during hypertrophy, and the downregulation of muscle-specific micro-RNA-1 correlated with the upregulation of five predicted targets associated with the integrin-linked kinase pathway. In conclusion, we identified two novel pathways that may be involved in muscle hypertrophy, as well as two upstream regulators (Kruppel-like factor-15 and micro-RNA-1) that provide targets for future studies investigating the importance of these pathways in muscle hypertrophy.

Archetypal analysis of diverse Pseudomonas aeruginosa transcriptomes reveals adaptation in cystic fibrosis airways

PubMed Central

2013-01-01

Background Analysis of global gene expression by DNA microarrays is widely used in experimental molecular biology. However, the complexity of such high-dimensional data sets makes it difficult to fully understand the underlying biological features present in the data. The aim of this study is to introduce a method for DNA microarray analysis that provides an intuitive interpretation of data through dimension reduction and pattern recognition. We present the first “Archetypal Analysis” of global gene expression. The analysis is based on microarray data from five integrated studies of Pseudomonas aeruginosa isolated from the airways of cystic fibrosis patients. Results Our analysis clustered samples into distinct groups with comprehensible characteristics since the archetypes representing the individual groups are closely related to samples present in the data set. Significant changes in gene expression between different groups identified adaptive changes of the bacteria residing in the cystic fibrosis lung. The analysis suggests a similar gene expression pattern between isolates with a high mutation rate (hypermutators) despite accumulation of different mutations for these isolates. This suggests positive selection in the cystic fibrosis lung environment, and changes in gene expression for these isolates are therefore most likely related to adaptation of the bacteria. Conclusions Archetypal analysis succeeded in identifying adaptive changes of P. aeruginosa. The combination of clustering and matrix factorization made it possible to reveal minor similarities among different groups of data, which other analytical methods failed to identify. We suggest that this analysis could be used to supplement current methods used to analyze DNA microarray data. PMID:24059747

Examination of the genetic basis for sexual dimorphism in the Aedes aegypti (dengue vector mosquito) pupal brain

PubMed Central

2014-01-01

Background Most animal species exhibit sexually dimorphic behaviors, many of which are linked to reproduction. A number of these behaviors, including blood feeding in female mosquitoes, contribute to the global spread of vector-borne illnesses. However, knowledge concerning the genetic basis of sexually dimorphic traits is limited in any organism, including mosquitoes, especially with respect to differences in the developing nervous system. Methods Custom microarrays were used to examine global differences in female vs. male gene expression in the developing pupal head of the dengue vector mosquito, Aedes aegypti. The spatial expression patterns of a subset of differentially expressed transcripts were examined in the developing female vs. male pupal brain through in situ hybridization experiments. Small interfering RNA (siRNA)-mediated knockdown studies were used to assess the putative role of Doublesex, a terminal component of the sex determination pathway, in the regulation of sex-specific gene expression observed in the developing pupal brain. Results Transcripts (2,527), many of which were linked to proteolysis, the proteasome, metabolism, catabolic, and biosynthetic processes, ion transport, cell growth, and proliferation, were found to be differentially expressed in A. aegypti female vs. male pupal heads. Analysis of the spatial expression patterns for a subset of dimorphically expressed genes in the pupal brain validated the data set and also facilitated the identification of brain regions with dimorphic gene expression. In many cases, dimorphic gene expression localized to the optic lobe. Sex-specific differences in gene expression were also detected in the antennal lobe and mushroom body. siRNA-mediated gene targeting experiments demonstrated that Doublesex, a transcription factor with consensus binding sites located adjacent to many dimorphically expressed transcripts that function in neural development, is required for regulation of sex-specific gene expression in the developing A. aegypti brain. Conclusions These studies revealed sex-specific gene expression profiles in the developing A. aegypti pupal head and identified Doublesex as a key regulator of sexually dimorphic gene expression during mosquito neural development. PMID:25729562

Brucella proteomes--a review.

PubMed

DelVecchio, Vito G; Wagner, Mary Ann; Eschenbrenner, Michel; Horn, Troy A; Kraycer, Jo Ann; Estock, Frank; Elzer, Phil; Mujer, Cesar V

2002-12-20

The proteomes of selected Brucella spp. have been extensively analyzed by utilizing current proteomic technology involving 2-DE and MALDI-MS. In Brucella melitensis, more than 500 proteins were identified. The rapid and large-scale identification of proteins in this organism was accomplished by using the annotated B. melitensis genome which is now available in the GenBank. Coupled with new and powerful tools for data analysis, differentially expressed proteins were identified and categorized into several classes. A global overview of protein expression patterns emerged, thereby facilitating the simultaneous analysis of different metabolic pathways in B. melitensis. Such a global characterization would not have been possible by using time consuming and traditional biochemical approaches. The era of post-genomic technology offers new and exciting opportunities to understand the complete biology of different Brucella species.

LateBiclustering: Efficient Heuristic Algorithm for Time-Lagged Bicluster Identification.

PubMed

Gonçalves, Joana P; Madeira, Sara C

2014-01-01

Identifying patterns in temporal data is key to uncover meaningful relationships in diverse domains, from stock trading to social interactions. Also of great interest are clinical and biological applications, namely monitoring patient response to treatment or characterizing activity at the molecular level. In biology, researchers seek to gain insight into gene functions and dynamics of biological processes, as well as potential perturbations of these leading to disease, through the study of patterns emerging from gene expression time series. Clustering can group genes exhibiting similar expression profiles, but focuses on global patterns denoting rather broad, unspecific responses. Biclustering reveals local patterns, which more naturally capture the intricate collaboration between biological players, particularly under a temporal setting. Despite the general biclustering formulation being NP-hard, considering specific properties of time series has led to efficient solutions for the discovery of temporally aligned patterns. Notably, the identification of biclusters with time-lagged patterns, suggestive of transcriptional cascades, remains a challenge due to the combinatorial explosion of delayed occurrences. Herein, we propose LateBiclustering, a sensible heuristic algorithm enabling a polynomial rather than exponential time solution for the problem. We show that it identifies meaningful time-lagged biclusters relevant to the response of Saccharomyces cerevisiae to heat stress.

Transcriptional dynamics of the developing sweet cherry (Prunus avium L.) fruit: sequencing, annotation and expression profiling of exocarp-associated genes

PubMed Central

Alkio, Merianne; Jonas, Uwe; Declercq, Myriam; Van Nocker, Steven; Knoche, Moritz

2014-01-01

The exocarp, or skin, of fleshy fruit is a specialized tissue that protects the fruit, attracts seed dispersing fruit eaters, and has large economical relevance for fruit quality. Development of the exocarp involves regulated activities of many genes. This research analyzed global gene expression in the exocarp of developing sweet cherry (Prunus avium L., ‘Regina’), a fruit crop species with little public genomic resources. A catalog of transcript models (contigs) representing expressed genes was constructed from de novo assembled short complementary DNA (cDNA) sequences generated from developing fruit between flowering and maturity at 14 time points. Expression levels in each sample were estimated for 34 695 contigs from numbers of reads mapping to each contig. Contigs were annotated functionally based on BLAST, gene ontology and InterProScan analyses. Coregulated genes were detected using partitional clustering of expression patterns. The results are discussed with emphasis on genes putatively involved in cuticle deposition, cell wall metabolism and sugar transport. The high temporal resolution of the expression patterns presented here reveals finely tuned developmental specialization of individual members of gene families. Moreover, the de novo assembled sweet cherry fruit transcriptome with 7760 full-length protein coding sequences and over 20 000 other, annotated cDNA sequences together with their developmental expression patterns is expected to accelerate molecular research on this important tree fruit crop. PMID:26504533

Seasonal Changes in Bacterial and Archaeal Gene Expression Patterns across Salinity Gradients in the Columbia River Coastal Margin

PubMed Central

Smith, Maria W.; Herfort, Lydie; Tyrol, Kaitlin; Suciu, Dominic; Campbell, Victoria; Crump, Byron C.; Peterson, Tawnya D.; Zuber, Peter; Baptista, Antonio M.; Simon, Holly M.

2010-01-01

Through their metabolic activities, microbial populations mediate the impact of high gradient regions on ecological function and productivity of the highly dynamic Columbia River coastal margin (CRCM). A 2226-probe oligonucleotide DNA microarray was developed to investigate expression patterns for microbial genes involved in nitrogen and carbon metabolism in the CRCM. Initial experiments with the environmental microarrays were directed toward validation of the platform and yielded high reproducibility in multiple tests. Bioinformatic and experimental validation also indicated that >85% of the microarray probes were specific for their corresponding target genes and for a few homologs within the same microbial family. The validated probe set was used to query gene expression responses by microbial assemblages to environmental variability. Sixty-four samples from the river, estuary, plume, and adjacent ocean were collected in different seasons and analyzed to correlate the measured variability in chemical, physical and biological water parameters to differences in global gene expression profiles. The method produced robust seasonal profiles corresponding to pre-freshet spring (April) and late summer (August). Overall relative gene expression was high in both seasons and was consistent with high microbial abundance measured by total RNA, heterotrophic bacterial production, and chlorophyll a. Both seasonal patterns involved large numbers of genes that were highly expressed relative to background, yet each produced very different gene expression profiles. April patterns revealed high differential gene expression in the coastal margin samples (estuary, plume and adjacent ocean) relative to freshwater, while little differential gene expression was observed along the river-to-ocean transition in August. Microbial gene expression profiles appeared to relate, in part, to seasonal differences in nutrient availability and potential resource competition. Furthermore, our results suggest that highly-active particle-attached microbiota in the Columbia River water column may perform dissimilatory nitrate reduction (both dentrification and DNRA) within anoxic particle microniches. PMID:20967204

Global assessment of small RNAs reveals a non-coding transcript involved in biofilm formation and attachment in Acinetobacter baumannii ATCC 17978

PubMed Central

Pérez, Astrid; Gómez, Manuel J.; Gayoso, Carmen; Vallejo, Juan A.; Ohneck, Emily J.; Valle, Jaione; Actis, Luis A.; Beceiro, Alejandro; Bou, Germán

2017-01-01

Many strains of Acinetobacter baumannii have been described as being able to form biofilm. Small non-coding RNAs (sRNAs) control gene expression in many regulatory circuits in bacteria. The aim of the present work was to provide a global description of the sRNAs produced both by planktonic and biofilm-associated (sessile) cells of A. baumannii ATCC 17978, and to compare the corresponding gene expression profiles to identify sRNAs molecules associated to biofilm formation and virulence. sRNA was extracted from both planktonic and sessile cells and reverse transcribed. cDNA was subjected to 454-pyrosequencing using the GS-FLX Titanium chemistry. The global analysis of the small RNA transcriptome revealed different sRNA expression patterns in planktonic and biofilm associated cells, with some of the transcripts only expressed or repressed in sessile bacteria. A total of 255 sRNAs were detected, with 185 of them differentially expressed in the different types of cells. A total of 9 sRNAs were expressed only in biofilm cells, while the expression of other 21 coding regions were repressed only in biofilm cells. Strikingly, the expression level of the sRNA 13573 was 120 times higher in biofilms than in planktonic cells, an observation that prompted us to further investigate the biological role of this non-coding transcript. Analyses of an isogenic mutant and over-expressing strains revealed that the sRNA 13573 gene is involved in biofilm formation and attachment to A549 human alveolar epithelial cells. The present work serves as a basis for future studies examining the complex regulatory network that regulate biofilm biogenesis and attachment to eukaryotic cells in A. baumannii ATCC 17978. PMID:28763494

Type of aphasia: relationship to age, sex, previous risk factors, and outcome of rehabilitation.

PubMed

Steinvil, Y; Ring, H; Luz, Y; Schechter, I; Solzi, P

1985-01-01

Relationship of types of aphasia in hemiplegics to survival, outcome of rehabilitation, activities of daily living (ADL) and pre-existing risk factors, hypertension (HT), ischemic heart disease (IHD), diabetes mellitus (DM) were studied in a group of 257 patients. The control group was a large population of CVA cases previously documented. Four main categories were considered: expressive-receptive (global), predominantly expressive (Broca), predominantly receptive (Wernicke) and predominantly amnestic (anomia) aphasias. 40% of each category were female. No clear pattern emerged concerning relationship with risk factors; however, hypertension, the factor most frequently encountered, was significantly less prevalent among expressive ahphasics, and diabetes mellitus was rare among those with the receptive pattern. For all categories, the most frequent etiology was thrombosis, the second being embolia. The oldest groups were the expressive-receptive and the predominantly receptive aphasia groups: showed the poorest rehabilitation outcome in both ADL and locomotion, and lived less time after stroke (5.8 years). Amnestic and expressive patients were younger and fared better in all other parameters; an etiology of embolia was much more frequent among the former. It can be said that patients with the expressive-receptive kind of aphasia have the worst survival and rehabilitation prognoses.

Digital gene expression analysis of gene expression differences within Brassica diploids and allopolyploids.

PubMed

Jiang, Jinjin; Wang, Yue; Zhu, Bao; Fang, Tingting; Fang, Yujie; Wang, Youping

2015-01-27

Brassica includes many successfully cultivated crop species of polyploid origin, either by ancestral genome triplication or by hybridization between two diploid progenitors, displaying complex repetitive sequences and transposons. The U's triangle, which consists of three diploids and three amphidiploids, is optimal for the analysis of complicated genomes after polyploidization. Next-generation sequencing enables the transcriptome profiling of polyploids on a global scale. We examined the gene expression patterns of three diploids (Brassica rapa, B. nigra, and B. oleracea) and three amphidiploids (B. napus, B. juncea, and B. carinata) via digital gene expression analysis. In total, the libraries generated between 5.7 and 6.1 million raw reads, and the clean tags of each library were mapped to 18547-21995 genes of B. rapa genome. The unambiguous tag-mapped genes in the libraries were compared. Moreover, the majority of differentially expressed genes (DEGs) were explored among diploids as well as between diploids and amphidiploids. Gene ontological analysis was performed to functionally categorize these DEGs into different classes. The Kyoto Encyclopedia of Genes and Genomes analysis was performed to assign these DEGs into approximately 120 pathways, among which the metabolic pathway, biosynthesis of secondary metabolites, and peroxisomal pathway were enriched. The non-additive genes in Brassica amphidiploids were analyzed, and the results indicated that orthologous genes in polyploids are frequently expressed in a non-additive pattern. Methyltransferase genes showed differential expression pattern in Brassica species. Our results provided an understanding of the transcriptome complexity of natural Brassica species. The gene expression changes in diploids and allopolyploids may help elucidate the morphological and physiological differences among Brassica species.

Zif268 mRNA Expression Patterns Reveal a Distinct Impact of Early Pattern Vision Deprivation on the Development of Primary Visual Cortical Areas in the Cat.

PubMed

Laskowska-Macios, Karolina; Zapasnik, Monika; Hu, Tjing-Tjing; Kossut, Malgorzata; Arckens, Lutgarde; Burnat, Kalina

2015-10-01

Pattern vision deprivation (BD) can induce permanent deficits in global motion perception. The impact of timing and duration of BD on the maturation of the central and peripheral visual field representations in cat primary visual areas 17 and 18 remains unknown. We compared early BD, from eye opening for 2, 4, or 6 months, with late onset BD, after 2 months of normal vision, using the expression pattern of the visually driven activity reporter gene zif268 as readout. Decreasing zif268 mRNA levels between months 2 and 4 characterized the normal maturation of the (supra)granular layers of the central and peripheral visual field representations in areas 17 and 18. In general, all BD conditions had higher than normal zif268 levels. In area 17, early BD induced a delayed decrease, beginning later in peripheral than in central area 17. In contrast, the decrease occurred between months 2 and 4 throughout area 18. Lack of pattern vision stimulation during the first 4 months of life therefore has a different impact on the development of areas 17 and 18. A high zif268 expression level at a time when normal vision is restored seems to predict the capacity of a visual area to compensate for BD. © The Author 2014. Published by Oxford University Press.

Specific Tandem 3'UTR Patterns and Gene Expression Profiles in Mouse Thy1+ Germline Stem Cells

PubMed Central

Lin, Zhuoheng; Feng, Xuyang; Jiang, Xue; Songyang, Zhou; Huang, Junjiu

2015-01-01

A recently developed strategy of sequencing alternative polyadenylation (APA) sites (SAPAS) with second-generation sequencing technology can be used to explore complete genome-wide patterns of tandem APA sites and global gene expression profiles. spermatogonial stem cells (SSCs) maintain long-term reproductive abilities in male mammals. The detailed mechanisms by which SSCs self-renew and generate mature spermatozoa are not clear. To understand the specific alternative polyadenylation pattern and global gene expression profile of male germline stem cells (GSCs, mainly referred to SSCs here), we isolated and purified mouse Thy1+ cells from testis by magnetic-activated cell sorting (MACS) and then used the SAPAS method for analysis, using pluripotent embryonic stem cells (ESCs) and differentiated mouse embryonic fibroblast cells (MEFs) as controls. As a result, we obtained 99,944 poly(A) sites, approximately 40% of which were newly detected in our experiments. These poly(A) sites originated from three mouse cell types and covered 17,499 genes, including 831 long non-coding RNA (lncRNA) genes. We observed that GSCs tend to have shorter 3'UTR lengths while MEFs tend towards longer 3'UTR lengths. We also identified 1337 genes that were highly expressed in GSCs, and these genes were highly consistent with the functional characteristics of GSCs. Our detailed bioinformatics analysis identified APA site-switching events at 3'UTRs and many new specifically expressed genes in GSCs, which we experimentally confirmed. Furthermore, qRT-PCR was performed to validate several events of the 334 genes with distal-to-proximal poly(A) switch in GSCs. Consistently APA reporter assay confirmed the total 3'UTR shortening in GSCs compared to MEFs. We also analyzed the cis elements around the proximal poly(A) site preferentially used in GSCs and found C-rich elements may contribute to this regulation. Overall, our results identified the expression level and polyadenylation site profiles and these data provide new insights into the processes potentially involved in the GSC life cycle and spermatogenesis. PMID:26713853

Gene expression profiling in Ishikawa cells: A fingerprint for estrogen active compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boehme, Kathleen; Simon, Stephanie; Mueller, Stefan O.

2009-04-01

Several anthropogenous and naturally occurring substances, referred to as estrogen active compounds (EACs), are able to interfere with hormone and in particular estrogen receptor signaling. EACs can either cause adverse health effects in humans and wildlife populations or have beneficial effects on estrogen-dependent diseases. The aim of this study was to examine global gene expression profiles in estrogen receptor (ER)-proficient Ishikawa plus and ER-deficient Ishikawa minus endometrial cancer cells treated with selected well-known EACs (Diethylstilbestrol, Genistein, Zearalenone, Resveratrol, Bisphenol A and o,p'-DDT). We also investigated the effect of the pure antiestrogen ICI 182,780 (ICI) on the expression patterns caused bymore » these compounds. Transcript levels were quantified 24 h after compound treatment using Illumina BeadChip Arrays. We identified 87 genes with similar expression changes in response to all EAC treatments in Ishikawa plus. ICI lowered the magnitude or reversed the expression of these genes, indicating ER dependent regulation. Apart from estrogenic gene regulation, Bisphenol A, o,p'-DDT, Zearalenone, Genistein and Resveratrol displayed similarities to ICI in their expression patterns, suggesting mixed estrogenic/antiestrogenic properties. In particular, the predominant antiestrogenic expression response of Resveratrol could be clearly distinguished from the other test compounds, indicating a distinct mechanism of action. Divergent gene expression patterns of the phytoestrogens, as well as weaker estrogenic gene expression regulation determined for the anthropogenous chemicals Bisphenol A and o,p'-DDT, warrants a careful assessment of potential detrimental and/or beneficial effects of EACs. The characteristic expression fingerprints and the identified subset of putative marker genes can be used for screening chemicals with an unknown mode of action and for predicting their potential to exert endocrine disrupting effects.« less

Flexible and inflexible task sets: asymmetric interference when switching between emotional expression, sex, and age classification of perceived faces.

PubMed

Schuch, Stefanie; Werheid, Katja; Koch, Iring

2012-01-01

The present study investigated whether the processing characteristics of categorizing emotional facial expressions are different from those of categorizing facial age and sex information. Given that emotions change rapidly, it was hypothesized that processing facial expressions involves a more flexible task set that causes less between-task interference than the task sets involved in processing age or sex of a face. Participants switched between three tasks: categorizing a face as looking happy or angry (emotion task), young or old (age task), and male or female (sex task). Interference between tasks was measured by global interference and response interference. Both measures revealed patterns of asymmetric interference. Global between-task interference was reduced when a task was mixed with the emotion task. Response interference, as measured by congruency effects, was larger for the emotion task than for the nonemotional tasks. The results support the idea that processing emotional facial expression constitutes a more flexible task set that causes less interference (i.e., task-set "inertia") than processing the age or sex of a face.

Medium-range Performance of the Global NWP Model

NASA Astrophysics Data System (ADS)

Kim, J.; Jang, T.; Kim, J.; Kim, Y.

2017-12-01

The medium-range performance of the global numerical weather prediction (NWP) model in the Korea Meteorological Administration (KMA) is investigated. The performance is based on the prediction of the extratropical circulation. The mean square error is expressed by sum of spatial variance of discrepancy between forecasts and observations and the square of the mean error (ME). Thus, it is important to investigate the ME effect in order to understand the model performance. The ME is expressed by the subtraction of an anomaly from forecast difference against the real climatology. It is found that the global model suffers from a severe systematic ME in medium-range forecasts. The systematic ME is dominant in the entire troposphere in all months. Such ME can explain at most 25% of root mean square error. We also compare the extratropical ME distribution with that from other NWP centers. NWP models exhibit similar spatial ME structure each other. It is found that the spatial ME pattern is highly correlated to that of an anomaly, implying that the ME varies with seasons. For example, the correlation coefficient between ME and anomaly ranges from -0.51 to -0.85 by months. The pattern of the extratropical circulation also has a high correlation to an anomaly. The global model has trouble in faithfully simulating extratropical cyclones and blockings in the medium-range forecast. In particular, the model has a hard to simulate an anomalous event in medium-range forecasts. If we choose an anomalous period for a test-bed experiment, we will suffer from a large error due to an anomaly.

Global miRNA expression profile reveals novel molecular players in aneurysmal subarachnoid haemorrhage.

PubMed

Lopes, Katia de Paiva; Vinasco-Sandoval, Tatiana; Vialle, Ricardo Assunção; Paschoal, Fernando Mendes; Bastos, Vanessa Albuquerque P Aviz; Bor-Seng-Shu, Edson; Teixeira, Manoel Jacobsen; Yamada, Elizabeth Sumi; Pinto, Pablo; Vidal, Amanda Ferreira; Ribeiro-Dos-Santos, Arthur; Moreira, Fabiano; Santos, Sidney; Paschoal, Eric Homero Albuquerque; Ribeiro-Dos-Santos, Ândrea

2018-06-08

The molecular mechanisms behind aneurysmal subarachnoid haemorrhage (aSAH) are still poorly understood. Expression patterns of miRNAs may help elucidate the post-transcriptional gene expression in aSAH. Here, we evaluate the global miRNAs expression profile (miRnome) of patients with aSAH to identify potential biomarkers. We collected 33 peripheral blood samples (27 patients with cerebral aneurysm, collected 7 to 10 days after the haemorrhage, when usually is the cerebral vasospasm risk peak, and six controls). Then, were performed small RNA sequencing using an Illumina Next Generation Sequencing (NGS) platform. Differential expression analysis identified eight differentially expressed miRNAs. Among them, three were identified being up-regulated, and five down-regulated. miR-486-5p was the most abundant expressed and is associated with poor neurological admission status. In silico miRNA gene target prediction showed 148 genes associated with at least two differentially expressed miRNAs. Among these, THBS1 and VEGFA, known to be related to thrombospondin and vascular endothelial growth factor. Moreover, MYC gene was found to be regulated by four miRNAs, suggesting an important role in aneurysmal subarachnoid haemorrhage. Additionally, 15 novel miRNAs were predicted being expressed only in aSAH, suggesting possible involvement in aneurysm pathogenesis. These findings may help the identification of novel biomarkers of clinical interest.

DNA methylation patterns and gene expression associated with litter size in Berkshire pig placenta

PubMed Central

Kwon, Seulgi; Park, Da Hye; Kim, Tae Wan; Kang, Deok Gyeong; Yu, Go Eun; Kim, Il-Suk; Park, Hwa Chun; Ha, Jeongim; Kim, Chul Wook

2017-01-01

Increasing litter size is of great interest to the pig industry. DNA methylation is an important epigenetic modification that regulates gene expression, resulting in livestock phenotypes such as disease resistance, milk production, and reproduction. We classified Berkshire pigs into two groups according to litter size and estimated breeding value: smaller (SLG) and larger (LLG) litter size groups. Genome-wide DNA methylation and gene expression were analyzed using placenta genomic DNA and RNA to identify differentially methylated regions (DMRs) and differentially expressed genes (DEGs) associated with litter size. The methylation levels of CpG dinucleotides in different genomic regions were noticeably different between the groups, while global methylation pattern was similar, and excluding intergenic regions they were found the most frequently in gene body regions. Next, we analyzed RNA-Seq data to identify DEGs between the SLG and LLG groups. A total of 1591 DEGs were identified: 567 were downregulated and 1024 were upregulated in LLG compared to SLG. To identify genes that simultaneously exhibited changes in DNA methylation and mRNA expression, we integrated and analyzed the data from bisulfite-Seq and RNA-Seq. Nine DEGs positioned in DMRs were found. The expression of only three of these genes (PRKG2, CLCA4, and PCK1) was verified by RT-qPCR. Furthermore, we observed the same methylation patterns in blood samples as in the placental tissues by PCR-based methylation analysis. Together, these results provide useful data regarding potential epigenetic markers for selecting hyperprolific sows. PMID:28880934

Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature

NASA Astrophysics Data System (ADS)

Dai, Guohao; Kaazempur-Mofrad, Mohammad R.; Natarajan, Sripriya; Zhang, Yuzhi; Vaughn, Saran; Blackman, Brett R.; Kamm, Roger D.; García-Cardeña, Guillermo; Gimbrone, Michael A., Jr.

2004-10-01

Atherosclerotic lesion localization to regions of disturbed flow within certain arterial geometries, in humans and experimental animals, suggests an important role for local hemodynamic forces in atherogenesis. To explore how endothelial cells (EC) acquire functional/dysfunctional phenotypes in response to vascular region-specific flow patterns, we have used an in vitro dynamic flow system to accurately reproduce arterial shear stress waveforms on cultured human EC and have examined the effects on EC gene expression by using a high-throughput transcriptional profiling approach. The flow patterns in the carotid artery bifurcations of several normal human subjects were characterized by using 3D flow analysis based on actual vascular geometries and blood flow profiles. Two prototypic arterial waveforms, "athero-prone" and "athero-protective," were defined as representative of the wall shear stresses in two distinct regions of the carotid artery (carotid sinus and distal internal carotid artery) that are typically "susceptible" or "resistant," respectively, to atherosclerotic lesion development. These two waveforms were applied to cultured EC, and cDNA microarrays were used to analyze the differential patterns of EC gene expression. In addition, the differential effects of athero-prone vs. athero-protective waveforms were further characterized on several parameters of EC structure and function, including actin cytoskeletal organization, expression and localization of junctional proteins, activation of the NF-B transcriptional pathway, and expression of proinflammatory cytokines and adhesion molecules. These global gene expression patterns and functional data reveal a distinct phenotypic modulation in response to the wall shear stresses present in atherosclerosis-susceptible vs. atherosclerosis-resistant human arterial geometries.

Hidden among the crowd: differential DNA methylation-expression correlations in cancer occur at important oncogenic pathways.

PubMed

Mosquera Orgueira, Adrián

2015-01-01

DNA methylation is a frequent epigenetic mechanism that participates in transcriptional repression. Variations in DNA methylation with respect to gene expression are constant, and, for unknown reasons, some genes with highly methylated promoters are sometimes overexpressed. In this study we have analyzed the expression and methylation patterns of thousands of genes in five groups of cancer and normal tissue samples in order to determine local and genome-wide differences. We observed significant changes in global methylation-expression correlation in all the neoplasms, which suggests that differential correlation events are frequent in cancer. A focused analysis in the breast cancer cohort identified 1662 genes whose correlation varies significantly between normal and cancerous breast, but whose DNA methylation and gene expression patterns do not change substantially. These genes were enriched in cancer-related pathways and repressive chromatin features across various model cell lines, such as PRC2 binding and H3K27me3 marks. Substantial changes in methylation-expression correlation indicate that these genes are subject to epigenetic remodeling, where the differential activity of other factors break the expected relationship between both variables. Our findings suggest a complex regulatory landscape where a redistribution of local and large-scale chromatin repressive domains at differentially correlated genes (DCGs) creates epigenetic hotspots that modulate cancer-specific gene expression.

Exploratory Investigation of Bacteroides fragilis Transcriptional Response during In vitro Exposure to Subinhibitory Concentration of Metronidazole.

PubMed

de Freitas, Michele C R; Resende, Juliana A; Ferreira-Machado, Alessandra B; Saji, Guadalupe D R Q; de Vasconcelos, Ana T R; da Silva, Vânia L; Nicolás, Marisa F; Diniz, Cláudio G

2016-01-01

Bacteroides fragilis , member from commensal gut microbiota, is an important pathogen associated to endogenous infections and metronidazole remains a valuable antibiotic for the treatment of these infections, although bacterial resistance is widely reported. Considering the need of a better understanding on the global mechanisms by which B. fragilis survive upon metronidazole exposure, we performed a RNA-seq transcriptomic approach with validation of gene expression results by qPCR. Bacteria strains were selected after in vitro subcultures with subinhibitory concentration (SIC) of the drug. From a wild type B. fragilis ATCC 43859 four derivative strains were selected: first and fourth subcultures under metronidazole exposure and first and fourth subcultures after drug removal. According to global gene expression analysis, 2,146 protein coding genes were identified, of which a total of 1,618 (77%) were assigned to a Gene Ontology term (GO), indicating that most known cellular functions were taken. Among these 2,146 protein coding genes, 377 were shared among all strains, suggesting that they are critical for B. fragilis survival. In order to identify distinct expression patterns, we also performed a K-means clustering analysis set to 15 groups. This analysis allowed us to detect the major activated or repressed genes encoding for enzymes which act in several metabolic pathways involved in metronidazole response such as drug activation, defense mechanisms against superoxide ions, high expression level of multidrug efflux pumps, and DNA repair. The strains collected after metronidazole removal were functionally more similar to those cultured under drug pressure, reinforcing that drug-exposure lead to drastic persistent changes in the B. fragilis gene expression patterns. These results may help to elucidate B. fragilis response during metronidazole exposure, mainly at SIC, contributing with information about bacterial survival strategies under stress conditions in their environment.

Two distinct auto-regulatory loops operate at the PU.1 locus in B cells and myeloid cells

PubMed Central

Leddin, Mathias; Perrod, Chiara; Hoogenkamp, Maarten; Ghani, Saeed; Assi, Salam; Heinz, Sven; Wilson, Nicola K.; Follows, George; Schönheit, Jörg; Vockentanz, Lena; Mosammam, Ali M.; Chen, Wei; Tenen, Daniel G.; Westhead, David R.; Göttgens, Berthold

2011-01-01

The transcription factor PU.1 occupies a central role in controlling myeloid and early B-cell development, and its correct lineage-specific expression is critical for the differentiation choice of hematopoietic progenitors. However, little is known of how this tissue-specific pattern is established. We previously identified an upstream regulatory cis element whose targeted deletion in mice decreases PU.1 expression and causes leukemia. We show here that the upstream regulatory cis element alone is insufficient to confer physiologic PU.1 expression in mice but requires the cooperation with other, previously unidentified elements. Using a combination of transgenic studies, global chromatin assays, and detailed molecular analyses we present evidence that PU.1 is regulated by a novel mechanism involving cross talk between different cis elements together with lineage-restricted autoregulation. In this model, PU.1 regulates its expression in B cells and macrophages by differentially associating with cell type–specific transcription factors at one of its cis-regulatory elements to establish differential activity patterns at other elements. PMID:21239694

Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters DNA methyltransferase (dnmt) expression in zebrafish (Danio rerio)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aluru, Neelakanteswar, E-mail: naluru@whoi.edu; Kuo, Elaine; Stanford University, 450 Serra Mall, Stanford, CA 94305

2015-04-15

DNA methylation is one of the most important epigenetic modifications involved in the regulation of gene expression. The DNA methylation reaction is catalyzed by DNA methyltransferases (DNMTs). Recent studies have demonstrated that toxicants can affect normal development by altering DNA methylation patterns, but the mechanisms of action are poorly understood. Hence, we tested the hypothesis that developmental exposure to TCDD affects dnmt gene expression patterns. Zebrafish embryos were exposed to 5 nM TCDD for 1 h from 4 to 5 h post-fertilization (hpf) and sampled at 12, 24, 48, 72, and 96 hpf to determine dnmt gene expression and DNAmore » methylation patterns. We performed a detailed analysis of zebrafish dnmt gene expression during development and in adult tissues. Our results demonstrate that dnmt3b genes are highly expressed in early stages of development, and dnmt3a genes are more abundant in later stages. TCDD exposure upregulated dnmt1 and dnmt3b2 expression, whereas dnmt3a1, 3b1, and 3b4 are downregulated following exposure. We did not observe any TCDD-induced differences in global methylation or hydroxymethylation levels, but the promoter methylation of aryl hydrocarbon receptor (AHR) target genes was altered. In TCDD-exposed embryos, AHR repressor a (ahrra) and c-fos promoters were differentially methylated. To characterize the TCDD effects on DNMTs, we cloned the dnmt promoters with xenobiotic response elements and conducted AHR transactivation assays using a luciferase reporter system. Our results suggest that ahr2 can regulate dnmt3a1, dnmt3a2, and dnmt3b2 expression. Overall, we demonstrate that developmental exposure to TCDD alters dnmt expression and DNA methylation patterns. - Highlights: • TCDD altered the dnmt expression in a gene and developmental time-specific manner. • TCDD hypermethylated ahrra and hypomethylated c-fos proximal promoter regions. • Functional analysis suggests that ahr2 can regulate dnmt3a1, 3a2, and 3b2 expression. • Dnmt3b genes are expressed early whereas dnmt3a are abundant later in development.« less

Altered in vivo left ventricular torsion and principal strains in hypothyroid rats

PubMed Central

Chen, Yong; Somji, Aleefia; Yu, Xin

2010-01-01

The twisting and untwisting motions of the left ventricle (LV) lead to efficient ejection of blood during systole and filling of the ventricle during diastole. Global LV mechanical performance is dependent on the contractile properties of cardiac myocytes; however, it is not known how changes in contractile protein expression affect the pattern and timing of LV rotation. At the myofilament level, contractile performance is largely dependent on the isoforms of myosin heavy chain (MHC) that are expressed. Therefore, in this study, we used MRI to examine the in vivo mechanical consequences of altered MHC isoform expression by comparing the contractile properties of hypothyroid rats, which expressed only the slow β-MHC isoform, and euthyroid rats, which predominantly expressed the fast α-MHC isoform. Unloaded shortening velocity (Vo) and apparent rate constants of force development (ktr) were measured in the skinned ventricular myocardium isolated from euthyroid and hypothyroid hearts. Increased expression of β-MHC reduced LV torsion and fiber strain and delayed the development of peak torsion and strain during systole. Depressed in vivo mechanical performance in hypothyroid rats was related to slowed cross-bridge performance, as indicated by significantly slower Vo and ktr, compared with euthyroid rats. Dobutamine infusion in hypothyroid hearts produced smaller increases in torsion and strain and aberrant transmural torsion patterns, suggesting that the myocardial response to β-adrenergic stress is compromised. Thus, increased expression of β-MHC alters the pattern and decreases the magnitude of LV rotation, contributing to reduced mechanical performance during systole, especially in conditions of increased workload. PMID:20729398

Correlated miR-mRNA expression signatures of mouse hematopoietic stem and progenitor cell subsets predict "Stemness" and "Myeloid" interaction networks.

PubMed

Heiser, Diane; Tan, Yee Sun; Kaplan, Ian; Godsey, Brian; Morisot, Sebastien; Cheng, Wen-Chih; Small, Donald; Civin, Curt I

2014-01-01

Several individual miRNAs (miRs) have been implicated as potent regulators of important processes during normal and malignant hematopoiesis. In addition, many miRs have been shown to fine-tune intricate molecular networks, in concert with other regulatory elements. In order to study hematopoietic networks as a whole, we first created a map of global miR expression during early murine hematopoiesis. Next, we determined the copy number per cell for each miR in each of the examined stem and progenitor cell types. As data is emerging indicating that miRs function robustly mainly when they are expressed above a certain threshold (∼100 copies per cell), our database provides a resource for determining which miRs are expressed at a potentially functional level in each cell type. Finally, we combine our miR expression map with matched mRNA expression data and external prediction algorithms, using a Bayesian modeling approach to create a global landscape of predicted miR-mRNA interactions within each of these hematopoietic stem and progenitor cell subsets. This approach implicates several interaction networks comprising a "stemness" signature in the most primitive hematopoietic stem cell (HSC) populations, as well as "myeloid" patterns associated with two branches of myeloid development.

Beta-catenin (CTNNB1) induces Bmp expression in urogenital sinus epithelium and participates in prostatic bud initiation and patterning

PubMed Central

Mehta, Vatsal; Schmitz, Christopher T.; Keil, Kimberly P.; Joshi, Pinak S.; Abler, Lisa L.; Lin, Tien-Min; Taketo, Makoto M.; Sun, Xin; Vezina, Chad M.

2013-01-01

Fetal prostate development is initiated by androgens and patterned by androgen dependent and independent signals. How these signals integrate to control epithelial cell differentiation and prostatic bud patterning is not fully understood. To test the role of beta-catenin (Ctnnb1) in this process, we used a genetic approach to conditionally delete or stabilize Ctnnb1 in urogenital sinus (UGS) epithelium from which the prostate derives. Two opposing mechanisms of action were revealed. By deleting Ctnnb1, we found it is required for separation of UGS from cloaca, emergence or maintenance of differentiated UGS basal epithelium and formation of prostatic buds. By genetically inducing a patchy subset of UGS epithelial cells to express excess CTNNB1, we found its excess abundance increases Bmp expression and leads to a global impairment of prostatic bud formation. Addition of NOGGIN partially restores prostatic budding in UGS explants with excess Ctnnb1. These results indicate a requirement for Ctnnb1 in UGS basal epithelial cell differentiation, prostatic bud initiation and bud spacing and suggest some of these actions are mediated in part through activation of BMP signaling. PMID:23396188

Candidate genes for cooperation and aggression in the social wasp Polistes dominula.

PubMed

Manfredini, Fabio; Brown, Mark J F; Toth, Amy L

2018-05-01

Cooperation and aggression are ubiquitous in social groups, and the genetic mechanisms underlying these behaviours are of great interest for understanding how social group formation is regulated and how it evolves. In this study, we used a candidate gene approach to investigate the patterns of expression of key genes for cooperation and aggression in the brain of a primitively eusocial wasp, Polistes dominula, during colony founding, when multiple foundresses can join the same nest and establish subtle hierarchies of dominance. We used a comparative approach to select candidate genes for cooperation and aggression looking at two previously published studies on global gene expression in wasps and ants. We tested the expression of these genes in P. dominula wasps that were either displaying aggressive behaviour (dominant and single foundresses) or cooperation (subordinate foundresses and workers) towards nestmates. One gene in particular, the egg yolk protein vitellogenin, known for its reproductive role in insects, displayed patterns of expression that strongly matched wasp social rank. We characterize the genomic context of vitellogenin by building a head co-expression gene network for P. dominula, and we discuss a potential role for vitellogenin as a mediator of social interactions in wasps.

Importance of correlation between gene expression levels: application to the type I interferon signature in rheumatoid arthritis.

PubMed

Reynier, Frédéric; Petit, Fabien; Paye, Malick; Turrel-Davin, Fanny; Imbert, Pierre-Emmanuel; Hot, Arnaud; Mougin, Bruno; Miossec, Pierre

2011-01-01

The analysis of gene expression data shows that many genes display similarity in their expression profiles suggesting some co-regulation. Here, we investigated the co-expression patterns in gene expression data and proposed a correlation-based research method to stratify individuals. Using blood from rheumatoid arthritis (RA) patients, we investigated the gene expression profiles from whole blood using Affymetrix microarray technology. Co-expressed genes were analyzed by a biclustering method, followed by gene ontology analysis of the relevant biclusters. Taking the type I interferon (IFN) pathway as an example, a classification algorithm was developed from the 102 RA patients and extended to 10 systemic lupus erythematosus (SLE) patients and 100 healthy volunteers to further characterize individuals. We developed a correlation-based algorithm referred to as Classification Algorithm Based on a Biological Signature (CABS), an alternative to other approaches focused specifically on the expression levels. This algorithm applied to the expression of 35 IFN-related genes showed that the IFN signature presented a heterogeneous expression between RA, SLE and healthy controls which could reflect the level of global IFN signature activation. Moreover, the monitoring of the IFN-related genes during the anti-TNF treatment identified changes in type I IFN gene activity induced in RA patients. In conclusion, we have proposed an original method to analyze genes sharing an expression pattern and a biological function showing that the activation levels of a biological signature could be characterized by its overall state of correlation.

Expression of the Retrotransposon Helena Reveals a Complex Pattern of TE Deregulation in Drosophila Hybrids

PubMed Central

Romero-Soriano, Valèria; Garcia Guerreiro, Maria Pilar

2016-01-01

Transposable elements (TEs), repeated mobile sequences, are ubiquitous in the eukaryotic kingdom. Their mobilizing capacity confers on them a high mutagenic potential, which must be strongly regulated to guarantee genome stability. In the Drosophila germline, a small RNA-mediated silencing system, the piRNA (Piwi-interacting RNA) pathway, is the main responsible TE regulating mechanism, but some stressful conditions can destabilize it. For instance, during interspecific hybridization, genomic stress caused by the shock of two different genomes can lead, in both animals and plants, to higher transposition rates. A recent study in D. buzatii—D. koepferae hybrids detected mobilization of 28 TEs, yet little is known about the molecular mechanisms explaining this transposition release. We have characterized one of the mobilized TEs, the retrotransposon Helena, and used quantitative expression to assess whether its high transposition rates in hybrids are preceded by increased expression. We have also localized Helena expression in the gonads to see if cellular expression patterns have changed in the hybrids. To give more insight into changes in TE regulation in hybrids, we analysed Helena-specific piRNA populations of hybrids and parental species. Helena expression is not globally altered in somatic tissues, but male and female gonads have different patterns of deregulation. In testes, Helena is repressed in F1, increasing then its expression up to parental values. This is linked with a mislocation of Helena transcripts along with an increase of their specific piRNA levels. Ovaries have additive levels of Helena expression, but the ping-pong cycle efficiency seems to be reduced in F1 hybrids. This could be at the origin of new Helena insertions in hybrids, which would be transmitted to F1 hybrid female progeny. PMID:26812285

Proteomic analysis of the bacterial cell cycle

PubMed Central

Grünenfelder, Björn; Rummel, Gabriele; Vohradsky, Jiri; Röder, Daniel; Langen, Hanno; Jenal, Urs

2001-01-01

A global approach was used to analyze protein synthesis and stability during the cell cycle of the bacterium Caulobacter crescentus. Approximately one-fourth (979) of the estimated C. crescentus gene products were detected by two-dimensional gel electrophoresis, 144 of which showed differential cell cycle expression patterns. Eighty-one of these proteins were identified by mass spectrometry and were assigned to a wide variety of functional groups. Pattern analysis revealed that coexpression groups were functionally clustered. A total of 48 proteins were rapidly degraded in the course of one cell cycle. More than half of these unstable proteins were also found to be synthesized in a cell cycle-dependent manner, establishing a strong correlation between rapid protein turnover and the periodicity of the bacterial cell cycle. This is, to our knowledge, the first evidence for a global role of proteolysis in bacterial cell cycle control. PMID:11287652

De novo analysis of the Nilaparvata lugens (Stål) antenna transcriptome and expression patterns of olfactory genes.

PubMed

Zhou, Shuang-Shuang; Sun, Ze; Ma, Weihua; Chen, Wei; Wang, Man-Qun

2014-03-01

We sequenced the antenna transcriptome of the brown planthopper (BPH), Nilaparvata lugens (Stål), a global rice pest, and performed transcriptome analysis on BPH antenna. We obtained about 40million 90bp reads that were assembled into 75,874 unigenes with a mean size of 456bp. Among the antenna transcripts, 32,856 (43%) showed significant similarity (E-value <1e(-5)) to known proteins in the NCBI database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to classify functions of BPH antenna genes. We identified 10 odorant-binding proteins (OBPs), including 7 previously unidentified, and 11 chemosensory proteins (CSPs), including two new members. The expression profiles of 4 OBPs and 2 CSPs were determined by q-PCR for antenna, abdomen, leg and wing of insects of different age, gender, and mating status including two BPH adult wing-morphology types. NlugCSP10 and 4 OBPs appeared to be antenna-specific because they were highly and differentially expressed in male and female antennae. NlugCSP11 was expressed ubiquitously, with particularly high expression in wings. The transcript levels of several olfactory genes depended on adult wing form, age, gender, and mating status, although no clear expression patterns were determined. Copyright © 2013 Elsevier Inc. All rights reserved.

Spectral biclustering of microarray data: coclustering genes and conditions.

PubMed

Kluger, Yuval; Basri, Ronen; Chang, Joseph T; Gerstein, Mark

2003-04-01

Global analyses of RNA expression levels are useful for classifying genes and overall phenotypes. Often these classification problems are linked, and one wants to find "marker genes" that are differentially expressed in particular sets of "conditions." We have developed a method that simultaneously clusters genes and conditions, finding distinctive "checkerboard" patterns in matrices of gene expression data, if they exist. In a cancer context, these checkerboards correspond to genes that are markedly up- or downregulated in patients with particular types of tumors. Our method, spectral biclustering, is based on the observation that checkerboard structures in matrices of expression data can be found in eigenvectors corresponding to characteristic expression patterns across genes or conditions. In addition, these eigenvectors can be readily identified by commonly used linear algebra approaches, in particular the singular value decomposition (SVD), coupled with closely integrated normalization steps. We present a number of variants of the approach, depending on whether the normalization over genes and conditions is done independently or in a coupled fashion. We then apply spectral biclustering to a selection of publicly available cancer expression data sets, and examine the degree to which the approach is able to identify checkerboard structures. Furthermore, we compare the performance of our biclustering methods against a number of reasonable benchmarks (e.g., direct application of SVD or normalized cuts to raw data).

Deep sequencing reveals cell-type-specific patterns of single-cell transcriptome variation.

PubMed

Dueck, Hannah; Khaladkar, Mugdha; Kim, Tae Kyung; Spaethling, Jennifer M; Francis, Chantal; Suresh, Sangita; Fisher, Stephen A; Seale, Patrick; Beck, Sheryl G; Bartfai, Tamas; Kuhn, Bernhard; Eberwine, James; Kim, Junhyong

2015-06-09

Differentiation of metazoan cells requires execution of different gene expression programs but recent single-cell transcriptome profiling has revealed considerable variation within cells of seeming identical phenotype. This brings into question the relationship between transcriptome states and cell phenotypes. Additionally, single-cell transcriptomics presents unique analysis challenges that need to be addressed to answer this question. We present high quality deep read-depth single-cell RNA sequencing for 91 cells from five mouse tissues and 18 cells from two rat tissues, along with 30 control samples of bulk RNA diluted to single-cell levels. We find that transcriptomes differ globally across tissues with regard to the number of genes expressed, the average expression patterns, and within-cell-type variation patterns. We develop methods to filter genes for reliable quantification and to calibrate biological variation. All cell types include genes with high variability in expression, in a tissue-specific manner. We also find evidence that single-cell variability of neuronal genes in mice is correlated with that in rats consistent with the hypothesis that levels of variation may be conserved. Single-cell RNA-sequencing data provide a unique view of transcriptome function; however, careful analysis is required in order to use single-cell RNA-sequencing measurements for this purpose. Technical variation must be considered in single-cell RNA-sequencing studies of expression variation. For a subset of genes, biological variability within each cell type appears to be regulated in order to perform dynamic functions, rather than solely molecular noise.

Gene stage-specific expression in the microenvironment of pediatric myelodysplastic syndromes.

PubMed

Roela, Rosimeire A; Carraro, Dirce M; Brentani, Helena P; Kaiano, Jane H L; Simão, Daniel F; Guarnieiro, Roberto; Lopes, Luiz Fernando; Borojevic, Radovan; Brentani, M Mitzi

2007-05-01

Using cDNA microarray assays we have observed a clear difference in the gene expression pattern between bone marrow stromal cells obtained from healthy children (CT) and from pediatric patients with either myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) associated with MDS (MDS-AML). The global gene function profiling analysis indicated that in the pediatric MDS microenvironment the disease stages may be characterized mainly by underexpression of genes associated with biological processes such as transport. Furthermore, a subset of downregulated genes related to endocytosis and protein secretion was able to discriminate MDS from MDS-AML.

Three Human Cell Types Respond to Multi-Walled Carbon Nanotubes and Titanium Dioxide Nanobelts with Cell-Specific Transcriptomic and Proteomic Expression Patterns.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tilton, Susan C.; Karin, Norman J.; Tolic, Ana

2014-08-01

The growing use of engineered nanoparticles (NPs) in commercial and medical applications raises the urgent need for tools that can predict NP toxicity. Global transcriptome and proteome analyses were conducted on three human cell types, exposed to two high aspect ratio NP types, to identify patterns of expression that might indicate high versus low NP toxicity. Three cell types representing the most common routes of human exposure to NPs, including macrophage-like (THP-1), small airway epithelial and intestinal (Caco-2/HT29-MTX) cells, were exposed to TiO2 nanobelts (TiO2-NB; high toxicity) and multi-walled carbon nanotubes (MWCNT; low toxicity) at low (10 µg/mL) and highmore » (100 µg/mL) concentrations for 1 and 24 h. Unique patterns of gene and protein expressions were identified for each cell type, with no differentially expressed (p < 0.05, 1.5-fold change) genes or proteins overlapping across all three cell types. While unique to each cell type, the early response was primarily independent of NP type, showing similar expression patterns in response to both TiO2-NB and MWCNT. The early response might, therefore, indicate a general response to insult. In contrast, the 24 h response was unique to each NP type. The most significantly (p < 0.05) enriched biological processes in THP-1 cells indicated TiO2-NB regulation of pathways associated with inflammation, apoptosis, cell cycle arrest, DNA replication stress and genomic instability, while MWCNT-regulated pathways indicated increased cell proliferation, DNA repair and anti-apoptosis. These two distinct sets of biological pathways might, therefore, underlie cellular responses to high and low NP toxicity, respectively.« less

Global DNA methylation in fetal human germ cells and germ cell tumours: association with differentiation and cisplatin resistance.

PubMed

Wermann, Hendrik; Stoop, Hans; Gillis, Ad J M; Honecker, Friedemann; van Gurp, Ruud J H L M; Ammerpohl, Ole; Richter, Julia; Oosterhuis, J Wolter; Bokemeyer, Carsten; Looijenga, Leendert H J

2010-08-01

Differences in the global methylation pattern, ie hyper- as well as hypo-methylation, are observed in cancers including germ cell tumours (GCTs). Related to their precursor cells, GCT methylation status differs according to histology. We investigated the methylation pattern of normal fetal, infantile, and adult germ cells (n = 103) and GCTs (n = 251) by immunohistochemical staining for 5-(m)cytidine. The global methylation pattern of male germ cells changes from hypomethylation to hypermethylation, whereas female germ cells remain unmethylated at all stages. Undifferentiated GCTs (seminomas, intratubular germ cell neoplasia unclassified, and gonadoblastomas) are hypomethylated, whereas more differentiated GCTs (teratomas, yolk sac tumours, and choriocarcinomas) show a higher degree of methylation. Embryonal carcinomas show an intermediate pattern. Resistance to cisplatin was assessed in the seminomatous cell line TCam-2 before and after demethylation using 5-azacytidine. Exposure to 5-azacytidine resulted in decreased resistance to cisplatin. Furthermore, after demethylation, the stem cell markers NANOG and POU5F1 (OCT3/4), as well as the germ cell-specific marker VASA, showed increased expression. Following treatment with 5-azacytidine, TCam-2 cells were analysed using a high-throughput methylation screen for changes in the methylation sites of 14,000 genes. Among the genes revealing changes, interesting targets were identified: ie demethylation of KLF11, a putative tumour suppressor gene, and hypermethylation of CFLAR, a gene previously described in treatment resistance in GCTs.

Profiles of Global Gene Expression in Ionizing-Radiation–Damaged Human Diploid Fibroblasts Reveal Synchronization behind the G1 Checkpoint in a G0-like State of Quiescence

PubMed Central

Zhou, Tong; Chou, Jeff W.; Simpson, Dennis A.; Zhou, Yingchun; Mullen, Thomas E.; Medeiros, Margarida; Bushel, Pierre R.; Paules, Richard S.; Yang, Xuebin; Hurban, Patrick; Lobenhofer, Edward K.; Kaufmann, William K.

2006-01-01

Cell cycle arrest and stereotypic transcriptional responses to DNA damage induced by ionizing radiation (IR) were quantified in telomerase-expressing human diploid fibroblasts. Analysis of cytotoxicity demonstrated that 1.5 Gy IR inactivated colony formation by 40–45% in three fibroblast lines; this dose was used in all subsequent analyses. Fibroblasts exhibited > 90% arrest of progression from G2 to M at 2 hr post-IR and a similarly severe arrest of progression from G1 to S at 6 and 12 hr post-IR. Normal rates of DNA synthesis and mitosis 6 and 12 hr post-IR caused the S and M compartments to empty by > 70% at 24 hr. Global gene expression was analyzed in IR-treated cells. A microarray analysis algorithm, EPIG, identified nine IR-responsive patterns of gene expression that were common to the three fibroblast lines, including a dominant p53-dependent G1 checkpoint response. Many p53 target genes, such as CDKN1A, GADD45, BTG2, and PLK3, were significantly up-regulated at 2 hr post-IR. Many genes whose expression is regulated by E2F family transcription factors, including CDK2, CCNE1, CDC6, CDC2, MCM2, were significantly down-regulated at 24 hr post-IR. Numerous genes that participate in DNA metabolism were also markedly repressed in arrested fibroblasts apparently as a result of cell synchronization behind the G1 checkpoint. However, cluster and principal component analyses of gene expression revealed a profile 24 hr post-IR with similarity to that of G0 growth quiescence. The results reveal a highly stereotypic pattern of response to IR in human diploid fibroblasts that reflects primarily synchronization behind the G1 checkpoint but with prominent induction of additional markers of G0 quiescence such as GAS1. PMID:16581545

DNA Methylation Mediated Control of Gene Expression Is Critical for Development of Crown Gall Tumors

PubMed Central

Kneitz, Susanne; Weber, Dana; Fuchs, Joerg; Hedrich, Rainer; Deeken, Rosalia

2013-01-01

Crown gall tumors develop after integration of the T-DNA of virulent Agrobacterium tumefaciens strains into the plant genome. Expression of the T-DNA–encoded oncogenes triggers proliferation and differentiation of transformed plant cells. Crown gall development is known to be accompanied by global changes in transcription, metabolite levels, and physiological processes. High levels of abscisic acid (ABA) in crown galls regulate expression of drought stress responsive genes and mediate drought stress acclimation, which is essential for wild-type-like tumor growth. An impact of epigenetic processes such as DNA methylation on crown gall development has been suggested; however, it has not yet been investigated comprehensively. In this study, the methylation pattern of Arabidopsis thaliana crown galls was analyzed on a genome-wide scale as well as at the single gene level. Bisulfite sequencing analysis revealed that the oncogenes Ipt, IaaH, and IaaM were unmethylated in crown galls. Nevertheless, the oncogenes were susceptible to siRNA–mediated methylation, which inhibited their expression and subsequently crown gall growth. Genome arrays, hybridized with methylated DNA obtained by immunoprecipitation, revealed a globally hypermethylated crown gall genome, while promoters were rather hypomethylated. Mutants with reduced non-CG methylation developed larger tumors than the wild-type controls, indicating that hypermethylation inhibits plant tumor growth. The differential methylation pattern of crown galls and the stem tissue from which they originate correlated with transcriptional changes. Genes known to be transcriptionally inhibited by ABA and methylated in crown galls became promoter methylated upon treatment of A. thaliana with ABA. This suggests that the high ABA levels in crown galls may mediate DNA methylation and regulate expression of genes involved in drought stress protection. In summary, our studies provide evidence that epigenetic processes regulate gene expression, physiological processes, and the development of crown gall tumors. PMID:23408907

DNA methylation mediated control of gene expression is critical for development of crown gall tumors.

PubMed

Gohlke, Jochen; Scholz, Claus-Juergen; Kneitz, Susanne; Weber, Dana; Fuchs, Joerg; Hedrich, Rainer; Deeken, Rosalia

2013-01-01

Crown gall tumors develop after integration of the T-DNA of virulent Agrobacterium tumefaciens strains into the plant genome. Expression of the T-DNA-encoded oncogenes triggers proliferation and differentiation of transformed plant cells. Crown gall development is known to be accompanied by global changes in transcription, metabolite levels, and physiological processes. High levels of abscisic acid (ABA) in crown galls regulate expression of drought stress responsive genes and mediate drought stress acclimation, which is essential for wild-type-like tumor growth. An impact of epigenetic processes such as DNA methylation on crown gall development has been suggested; however, it has not yet been investigated comprehensively. In this study, the methylation pattern of Arabidopsis thaliana crown galls was analyzed on a genome-wide scale as well as at the single gene level. Bisulfite sequencing analysis revealed that the oncogenes Ipt, IaaH, and IaaM were unmethylated in crown galls. Nevertheless, the oncogenes were susceptible to siRNA-mediated methylation, which inhibited their expression and subsequently crown gall growth. Genome arrays, hybridized with methylated DNA obtained by immunoprecipitation, revealed a globally hypermethylated crown gall genome, while promoters were rather hypomethylated. Mutants with reduced non-CG methylation developed larger tumors than the wild-type controls, indicating that hypermethylation inhibits plant tumor growth. The differential methylation pattern of crown galls and the stem tissue from which they originate correlated with transcriptional changes. Genes known to be transcriptionally inhibited by ABA and methylated in crown galls became promoter methylated upon treatment of A. thaliana with ABA. This suggests that the high ABA levels in crown galls may mediate DNA methylation and regulate expression of genes involved in drought stress protection. In summary, our studies provide evidence that epigenetic processes regulate gene expression, physiological processes, and the development of crown gall tumors.

Methane monooxygenase gene expression mediated by methanobactin in the presence of mineral copper sources

PubMed Central

Knapp, Charles W.; Fowle, David A.; Kulczycki, Ezra; Roberts, Jennifer A.; Graham, David W.

2007-01-01

Methane is a major greenhouse gas linked to global warming; however, patterns of in situ methane oxidation by methane-oxidizing bacteria (methanotrophs), nature's main biological mechanism for methane suppression, are often inconsistent with laboratory predictions. For example, one would expect a strong relationship between methanotroph ecology and Cu level because methanotrophs require Cu to sustain particulate methane monooxygenase (pMMO), the most efficient enzyme for methane oxidation. However, no correlation has been observed in nature, which is surprising because methane monooxygenase (MMO) gene expression has been unequivocally linked to Cu availability. Here we provide a fundamental explanation for this lack of correlation. We propose that MMO expression in nature is largely controlled by solid-phase Cu geochemistry and the relative ability of Cu acquisition systems in methanotrophs, such as methanobactins (mb), to obtain Cu from mineral sources. To test this hypothesis, RT-PCR expression assays were developed for Methylosinus trichosporium OB3b (which produces mb) to quantify pMMO, soluble MMO (the alternate MMO expressed when Cu is “unavailable”), and 16S-rRNA gene expression under progressively more stringent Cu supply conditions. When Cu was provided as CuCl2, pMMO transcript levels increased significantly consistent with laboratory work. However, when Cu was provided as Cu-doped iron oxide, pMMO transcript levels increased only when mb was also present. Finally, when Cu was provided as Cu-doped borosilicate glass, pMMO transcription patterns varied depending on the ambient mb:Cu supply ratio. Cu geochemistry clearly influences MMO expression in terrestrial systems, and, as such, local Cu mineralogy might provide an explanation for methane oxidation patterns in the natural environment. PMID:17615240

Hypoxia regulates microRNA expression in the human carotid body

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mkrtchian, Souren, E-mail: souren.mkrtchian@ki.se; Lee, Kian Leong, E-mail: csilkl@nus.edu.sg; Kåhlin, Jessica

The carotid body (CB) is the key sensing organ for physiological oxygen levels in the body. Under conditions of low oxygen (hypoxia), the CB plays crucial roles in signaling to the cardiorespiratory center in the medulla oblongata for the restoration of oxygen homeostasis. How hypoxia regulates gene expression in the human CB remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the identity and impact of important post-transcriptional regulators such as non-coding RNAs, and in particular miRNAs are not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentiallymore » regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating that they may have the most similar developmental origins. - Highlights: • Hypoxia triggers differential expression of many miRNAs in the human carotid body. • This can lead to the upregulation of proliferation and immune response functions. • CB expression profile in the carotid body resembles the miRNA expression pattern in the brain. • miRNAs are involved in the regulation of carotid body functions including oxygen sensing.« less

Hidden among the crowd: differential DNA methylation-expression correlations in cancer occur at important oncogenic pathways

PubMed Central

Mosquera Orgueira, Adrián

2015-01-01

DNA methylation is a frequent epigenetic mechanism that participates in transcriptional repression. Variations in DNA methylation with respect to gene expression are constant, and, for unknown reasons, some genes with highly methylated promoters are sometimes overexpressed. In this study we have analyzed the expression and methylation patterns of thousands of genes in five groups of cancer and normal tissue samples in order to determine local and genome-wide differences. We observed significant changes in global methylation-expression correlation in all the neoplasms, which suggests that differential correlation events are frequent in cancer. A focused analysis in the breast cancer cohort identified 1662 genes whose correlation varies significantly between normal and cancerous breast, but whose DNA methylation and gene expression patterns do not change substantially. These genes were enriched in cancer-related pathways and repressive chromatin features across various model cell lines, such as PRC2 binding and H3K27me3 marks. Substantial changes in methylation-expression correlation indicate that these genes are subject to epigenetic remodeling, where the differential activity of other factors break the expected relationship between both variables. Our findings suggest a complex regulatory landscape where a redistribution of local and large-scale chromatin repressive domains at differentially correlated genes (DCGs) creates epigenetic hotspots that modulate cancer-specific gene expression. PMID:26029238

Collaborations between CpG sites in DNA methylation

NASA Astrophysics Data System (ADS)

Song, You; Ren, Honglei; Lei, Jinzhi

2017-08-01

DNA methylation patterns have profound impacts on genome stability, gene expression and development. The molecular base of DNA methylation patterns has long been focused at single CpG sites level. Here, we construct a kinetic model of DNA methylation with collaborations between CpG sites, from which a correlation function was established based on experimental data. The function consists of three parts that suggest three possible sources of the correlation: movement of enzymes along DNA, collaboration between DNA methylation and nucleosome modification, and global enzyme concentrations within a cell. Moreover, the collaboration strength between DNA methylation and nucleosome modification is universal for mouse early embryo cells. The obtained correlation function provides insightful understanding for the mechanisms of inheritance of DNA methylation patterns.

Environmental forcing of terrestrial carbon isotope excursion amplification across five Eocene hyperthermals

NASA Astrophysics Data System (ADS)

Bowen, G. J.; Abels, H.

2015-12-01

Abrupt changes in the isotope composition of exogenic carbon pools accompany many major episodes of global change in the geologic record. The global expression of this change in substrates that reflect multiple carbon pools provides important evidence that many events reflect persistent, global redistribution of carbon between reduced and oxidized stocks. As the diversity of records documenting any event grows, however, discrepancies in the expression of carbon isotope change among substrates are almost always revealed. These differences in magnitude, pace, and pattern of change can complicate interpretations of global carbon redistribution, but under ideal circumstances can also provide additional information on changes in specific environmental and biogeochemical systems that accompanied the global events. Here we evaluate possible environmental influences on new terrestrial records of the negative carbon isotope excursions (CIEs) associated with multiple hyperthermals of the Early Eocene, which show a common pattern of amplified carbon isotope change in terrestrial paleosol carbonate records relative to that recorded in marine substrates. Scaling relationships between climate and carbon-cycle proxies suggest that that the climatic (temperature) impact of each event scaled proportionally with the magnitude of its marine CIE, likely implying that all events involved release of reduced carbon with a similar isotopic composition. Amplification of the terrestrial CIEs, however, does not scale with event magnitude, being proportionally less for the first, largest event (the PETM). We conduct a sensitivity test of a coupled plant-soil carbon isotope model to identify conditions that could account for the observed CIE scaling. At least two possibilities consistent with independent lines of evidence emerge: first, varying effects of pCO2 change on photosynthetic carbon isotope discrimination under changing background pCO2, and second, contrasting changes in regional hydroclimate during the PETM and subsequent hyperthermals. These mechanisms have very different implications for the reconstruction of environmental conditions, and resolving the correct interpretation will require new, complimentary records of plant and soil conditions associated with the Early Eocene hyperthermals.

Neuroendocrine and immune network re-modeling in chronic fatigue syndrome: an exploratory analysis.

PubMed

Fuite, Jim; Vernon, Suzanne D; Broderick, Gordon

2008-12-01

This work investigates the significance of changes in association patterns linking indicators of neuroendocrine and immune activity in patients with chronic fatigue syndrome (CFS). Gene sets preferentially expressed in specific immune cell isolates were integrated with neuroendocrine data from a large population-based study. Co-expression patterns linking immune cell activity with hypothalamic-pituitary-adrenal (HPA), thyroidal (HPT) and gonadal (HPG) axis status were computed using mutual information criteria. Networks in control and CFS subjects were compared globally in terms of a weighted graph edit distance. Local re-modeling of node connectivity was quantified by node degree and eigenvector centrality measures. Results indicate statistically significant differences between CFS and control networks determined mainly by re-modeling around pituitary and thyroid nodes as well as an emergent immune sub-network. Findings align with known mechanisms of chronic inflammation and support possible immune-mediated loss of thyroid function in CFS exacerbated by blunted HPA axis responsiveness.

Pattern recognition receptor immunomodulation of innate immunity as a strategy to limit the impact of influenza virus.

PubMed

Pizzolla, Angela; Smith, Jeffery M; Brooks, Andrew G; Reading, Patrick C

2017-04-01

Influenza remains a major global health issue and the effectiveness of current vaccines and antiviral drugs is limited by the continual evolution of influenza viruses. Therefore, identifying novel prophylactic or therapeutic treatments that induce appropriate innate immune responses to protect against influenza infection would represent an important advance in efforts to limit the impact of influenza. Cellular pattern recognition receptors (PRRs) recognize conserved structures expressed by pathogens to trigger intracellular signaling cascades, promoting expression of proinflammatory molecules and innate immunity. Therefore, a number of approaches have been developed to target specific PRRs in an effort to stimulate innate immunity and reduce disease in a variety of settings, including during influenza infections. Herein, we discuss progress in immunomodulation strategies designed to target cell-associated PRRs of the innate immune system, thereby, modifying innate responses to IAV infection and/or augmenting immune responses to influenza vaccines. © Society for Leukocyte Biology.

Patterns Cancer Prevention Through Induction of Phase 2 Enzymes

DTIC Science & Technology

2003-04-01

2) enzymes. During our Phase I Award, we identified sulforaphane as the most potent inducer of carcinogen defenses in the prostate cell. We have...characterized global effects of sulforaphane in prostate cancer cell lines using cDNA microarray technology that allows large-scale determination of...changes in gene expression. These findings argue strongly for a preventive intervention trial involving with sulforaphane . During our Phase 2 Award, we used

Nitric oxide deficiency determines global chromatin changes in Duchenne muscular dystrophy.

PubMed

Colussi, Claudia; Gurtner, Aymone; Rosati, Jessica; Illi, Barbara; Ragone, Gianluca; Piaggio, Giulia; Moggio, Maurizio; Lamperti, Costanza; D'Angelo, Grazia; Clementi, Emilio; Minetti, Giulia; Mozzetta, Chiara; Antonini, Annalisa; Capogrossi, Maurizio C; Puri, Pier Lorenzo; Gaetano, Carlo

2009-07-01

The present study provides evidence that abnormal patterns of global histone modification are present in the skeletal muscle nuclei of mdx mice and Duchenne muscular dystrophy (DMD) patients. A combination of specific histone H3 modifications, including Ser-10 phosphorylation, acetylation of Lys 9 and 14, and Lys 79 methylation, were found enriched in muscle biopsies from human patients affected by DMD and in late-term fetuses, early postnatal pups, or adult mdx mice. In this context, chromatin immunoprecipitation experiments showed an enrichment of these modifications at the loci of genes involved in proliferation or inflammation, suggesting a regulatory effect on gene expression. Remarkably, the reexpression of dystrophin induced by gentamicin treatment or the administration of nitric oxide (NO) donors reversed the abnormal pattern of H3 histone modifications. These findings suggest an unanticipated link between the dystrophin-activated NO signaling and the remodeling of chromatin. In this context, the regulation of class IIa histone deacetylases (HDACs) 4 and 5 was found altered as a consequence of the reduced NO-dependent protein phosphatase 2A activity, indicating that both NO and class IIa HDACs are important for satellite cell differentiation and gene expression in mdx mice. In conclusion, this work provides the first evidence of a role for NO as an epigenetic regulator in DMD.

Global effects of the DEAD-box RNA helicase DeaD (CsdA) on gene expression over a broad range of temperatures

PubMed Central

Vakulskas, Christopher A.; Pannuri, Archana; Cortés-Selva, Diana; Zere, Tesfalem R.; Ahmer, Brian M.; Babitzke, Paul; Romeo, Tony

2014-01-01

Summary In Escherichia coli, activity of the global regulatory RNA binding protein CsrA is antagonized by two noncoding sRNAs, CsrB and CsrC, which sequester it away from its lower affinity mRNA targets. Transcription of csrB/C requires the BarA-UvrY two component signal transduction system, which responds to short chain carboxylates. We show that two DEAD-box RNA helicases, DeaD and SrmB, activate csrB/C expression by different pathways. DeaD facilitates uvrY translation by counteracting the inhibitory effect of long distance basepairing between the uvrY mRNA leader and coding region, while SrmB does not affect UvrY or UvrY-phosphate levels. Contrary to the prevailing notion that these helicases act primarily at low temperatures, DeaD and SrmB activated csrB expression over a wide temperature range. High-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) revealed in vivo interactions of DeaD with 39 mRNAs, including those of uvrY and 9 other regulatory genes. Studies on the expression of several of the identified genes revealed regulatory effects of DeaD in all cases and diverse temperature response patterns. Our findings uncover an expanded regulatory role for DeaD, which is mediated through novel mRNA targets, important global regulators and under physiological conditions that were considered to be incompatible with its function. PMID:24708042

Fifty Years of Water Cycle Change expressed in Ocean Salinity

NASA Astrophysics Data System (ADS)

Durack, P. J.; Wijffels, S.

2010-12-01

Using over 1.6 million profiles of salinity, potential temperature and density from historical archives and Argo, we derive the global field of linear change for ocean state properties over the period 1950-2008, taking care to minimise aliasing associated with seasonal and El Nino Southern Oscillation modes. We find large, robust and spatially coherent multi-decadal linear trends in ocean surface salinities. Increases are found in evaporation-dominated regions and freshening in precipitation-dominated regions. The spatial patterns of surface change strongly resemble the climatological mean surface salinity field, consistent with an amplification of the global water cycle. A robust amplification of the mean salinity pattern of 8% (to 200m depth) is found globally and 5-9% is found in each of the 3 key ocean basins. 20th century runs from the CMIP3 model suite support the relationship between amplified patterns of freshwater flux driving an amplified pattern of ocean surface salinity only in models that warm substantially. Models with volcanic aerosols show a diminished warming response and a corresponding weak response in ocean surface salinity change, which implies dampened changes to the global water cycle. The warming response represented in realistic (when compared to observations) 20th century simulations appear quite similar in their broad zonal patterns to those of the projected 21st century simulations, these projected runs being strongly forced by greenhouse gases. This pattern amplification is mostly absent from 20th century simulations which include volcanic forcing. While we confirm that global mean precipitation only weakly change with surface warming (2-3% K-1), the pattern amplification rate in both the freshwater flux and ocean salinity fields indicate larger responses. Our new observed salinity estimates suggest a change of between 8-16% K-1, close to, or greater than, the theoretical response described by the Clausius-Clapeyron relation. The underestimation of change patterns by the CMIP3 model suite is well documented in recent literature describing changes to the atmospheric and terrestrial arms of the global water cycle. These new observational ocean results add emphasis to the conclusion that the rate of observed changes in the 20th century are larger than CMIP3 models, and simplified physical theories predict. A) The 50-year linear surface salinity trend (pss/50-years). Contours every 0.25 pss are plotted in white. B) Ocean-atmosphere freshwater flux (m3 yr-1) averaged over 1980-1993 (Josey et al., 1998). Contours every 1 m3 yr-1 are in white. On both panels, the 1975 surface mean salinity is contoured black (contour interval 0.5 pss for thin lines, 1 for thick lines).

Expression of pathogenicity-related genes of Xylella fastidiosa in vitro and in planta.

PubMed

de Souza, Alessandra A; Takita, Marco A; Pereira, Eridan O; Coletta-Filho, Helvécio D; Machado, Marcos A

2005-04-01

Xylella fastidiosa is responsible for several economically important plant diseases. It is currently assumed that the symptoms are caused by vascular occlusion due to biofilm formation. Microarray technology was previously used to examine the global gene expression profile of X. fastidiosa freshly isolated from symptomatic plants or after several passages by axenic culture medium, and different pathogenicity profiles have been obtained. In the present study the expression of some pathogenicity-related genes was evaluated in vitro and in planta by RT-PCR. The results suggest that adhesion is important at the beginning of biofilm formation, while the genes related to adaptation are essential for the organism's maintenance in planta. Similar results were observed in vitro mainly for the adhesion genes. The pattern of expression observed suggests that adhesion modulates biofilm formation whereas the expression of some adaptation genes may be related to the environment in which the organism is living.

Terrestrial Feedbacks Incorporated in Global Vegetation Models through Observed Trait-Environment Responses

NASA Astrophysics Data System (ADS)

Bodegom, P. V.

2015-12-01

Most global vegetation models used to evaluate climate change impacts rely on plant functional types to describe vegetation responses to environmental stresses. In a traditional set-up in which vegetation characteristics are considered constant within a vegetation type, the possibility to implement and infer feedback mechanisms are limited as feedback mechanisms will likely involve a changing expression of community trait values. Based on community assembly concepts, we implemented functional trait-environment relationships into a global dynamic vegetation model to quantitatively assess this feature. For the current climate, a different global vegetation distribution was calculated with and without the inclusion of trait variation, emphasizing the importance of feedbacks -in interaction with competitive processes- for the prevailing global patterns. These trait-environmental responses do, however, not necessarily imply adaptive responses of vegetation to changing conditions and may locally lead to a faster turnover in vegetation upon climate change. Indeed, when running climate projections, simulations with trait variation did not yield a more stable or resilient vegetation than those without. Through the different feedback expressions, global and regional carbon and water fluxes were -however- strongly altered. At a global scale, model projections suggest an increased productivity and hence an increased carbon sink in the next decades to come, when including trait variation. However, by the end of the century, a reduced carbon sink is projected. This effect is due to a downregulation of photosynthesis rates, particularly in the tropical regions, even when accounting for CO2-fertilization effects. Altogether, the various global model simulations suggest the critical importance of including vegetation functional responses to changing environmental conditions to grasp terrestrial feedback mechanisms at global scales in the light of climate change.

Chromosome Transfer Induced Aneuploidy Results in Complex Dysregulation of the Cellular Transcriptome in Immortalized and Cancer Cells

PubMed Central

Upender, Madhvi B.; Habermann, Jens K.; McShane, Lisa M.; Korn, Edward L.; Barrett, J. Carl; Difilippantonio, Michael J.; Ried, Thomas

2016-01-01

Chromosomal aneuploidies are observed in essentially all sporadic carcinomas. These aneuploidies result in tumor-specific patterns of genomic imbalances that are acquired early during tumorigenesis, continuously selected for and faithfully maintained in cancer cells. Although the paradigm of translocation induced oncogene activation in hematologic malignancies is firmly established, it is not known how genomic imbalances affect chromosome-specific gene expression patterns in particular and how chromosomal aneuploidy dysregulates the genetic equilibrium of cells in general. To model specific chromosomal aneuploidies in cancer cells and dissect the immediate consequences of genomic imbalances on the transcriptome, we generated artificial trisomies in a karyotypically stable diploid yet mismatch repair-deficient, colorectal cancer cell line and in telomerase immortalized, cytogenetically normal human breast epithelial cells using microcell-mediated chromosome transfer. The global consequences on gene expression levels were analyzed using cDNA arrays. Our results show that regardless of chromosome or cell type, chromosomal trisomies result in a significant increase in the average transcriptional activity of the trisomic chromosome. This increase affects the expression of numerous genes on other chromosomes as well. We therefore postulate that the genomic imbalances observed in cancer cells exert their effect through a complex pattern of transcriptional dysregulation. PMID:15466185

Integrated Analysis of Alzheimer's Disease and Schizophrenia Dataset Revealed Different Expression Pattern in Learning and Memory.

PubMed

Li, Wen-Xing; Dai, Shao-Xing; Liu, Jia-Qian; Wang, Qian; Li, Gong-Hua; Huang, Jing-Fei

2016-01-01

Alzheimer's disease (AD) and schizophrenia (SZ) are both accompanied by impaired learning and memory functions. This study aims to explore the expression profiles of learning or memory genes between AD and SZ. We downloaded 10 AD and 10 SZ datasets from GEO-NCBI for integrated analysis. These datasets were processed using RMA algorithm and a global renormalization for all studies. Then Empirical Bayes algorithm was used to find the differentially expressed genes between patients and controls. The results showed that most of the differentially expressed genes were related to AD whereas the gene expression profile was little affected in the SZ. Furthermore, in the aspects of the number of differentially expressed genes, the fold change and the brain region, there was a great difference in the expression of learning or memory related genes between AD and SZ. In AD, the CALB1, GABRA5, and TAC1 were significantly downregulated in whole brain, frontal lobe, temporal lobe, and hippocampus. However, in SZ, only two genes CRHBP and CX3CR1 were downregulated in hippocampus, and other brain regions were not affected. The effect of these genes on learning or memory impairment has been widely studied. It was suggested that these genes may play a crucial role in AD or SZ pathogenesis. The different gene expression patterns between AD and SZ on learning and memory functions in different brain regions revealed in our study may help to understand the different mechanism between two diseases.

Epigenetic control of skull morphogenesis by histone deacetylase 8

PubMed Central

Haberland, Michael; Mokalled, Mayssa H.; Montgomery, Rusty L.; Olson, Eric N.

2009-01-01

Histone deacetylases (Hdacs) are transcriptional repressors with crucial roles in mammalian development. Here we provide evidence that Hdac8 specifically controls patterning of the skull by repressing a subset of transcription factors in cranial neural crest cells. Global deletion of Hdac8 in mice leads to perinatal lethality due to skull instability, and this is phenocopied by conditional deletion of Hdac8 in cranial neural crest cells. Hdac8 specifically represses the aberrant expression of homeobox transcription factors such as Otx2 and Lhx1. These findings reveal how the identity and patterning of vertebrate-specific portions of the skull are epigenetically controlled by a histone deacetylase. PMID:19605684

The surface and deep structure of the waterfall illusion.

PubMed

Wade, Nicholas J; Ziefle, Martina

2008-11-01

The surface structure of the waterfall illusion or motion aftereffect (MAE) is its phenomenal visibility. Its deep structure will be examined in the context of a model of space and motion perception. The MAE can be observed following protracted observation of a pattern that is translating, rotating, or expanding/contracting, a static pattern appears to move in the opposite direction. The phenomenon has long been known, and it continues to present novel properties. One of the novel features of MAEs is that they can provide an ideal visual assay for distinguishing local from global processes. Motion during adaptation can be induced in a static central grating by moving surround gratings; the MAE is observed in the static central grating but not in static surrounds. The adaptation phase is local and the test phase is global. That is, localised adaptation can be expressed in different ways depending on the structure of the test display. These aspects of MAEs can be exploited to determine a variety of local/global interactions. Six experiments on MAEs are reported. The results indicated that relational motion is required to induce an MAE; the region adapted extends beyond that stimulated; storage can be complete when the MAE is not seen during the storage period; interocular transfer (IOT) is around 30% of monocular MAEs with phase alternation; large field spiral patterns yield MAEs with characteristic monocular and binocular interactions.

Localization of DNA methyltransferase-1 during oocyte differentiation, in vitro maturation and early embryonic development in cow

PubMed Central

Lodde, V.; Modina, S.C.; Franciosi, F.; Zuccari, E.; Tessaro, I.; Luciano, A.M.

2009-01-01

DNA methyltransferase-1 (Dnmt1) is involved in the maintenance of DNA methylation patterns and is crucial for normal mammalian development. The aim of the present study was to assess the localization of Dnmt1 in cow, during the latest phases of oocyte differentiation and during the early stages of segmentation. Dnmt1 expression and localization were assessed in oocytes according to the chromatin configuration, which in turn provides an important epigenetic mechanism for the control of global gene expression and represents a morphological marker of oocyte differentiation. We found that the initial chromatin condensation was accompanied by a slight increase in the level of global DNA methylation, as assessed by 5-methyl-cytosine immunostaining followed by laser scanning confocal microscopy analysis (LSCM). RT-PCR confirmed the presence of Dnmt1 transcripts throughout this phase of oocyte differentiation. Analogously, Dnmt1 immunodetection and LSCM indicated that the protein was always present and localized in the cytoplasm, regardless the chromatin configuration and the level of global DNA methylation. Moreover, our data indicate that while Dnmt1 is retained in the cytoplasm in metaphase II stage oocytes and zygotes, it enters the nuclei of 8–16 cell stage embryos. As suggested in mouse, the functional meaning of the presence of Dnmt1 in the bovine embryo nuclei could be the maintainement of the methylation pattern of imprinted genes. In conclusion, the present work provides useful elements for the study of Dnmt1 function during the late stage of oocyte differentiation, maturation and early embryonic development in mammals. PMID:22073356

Defective Cell Cycle Checkpoint Functions in Melanoma Are Associated with Altered Patterns of Gene Expression

PubMed Central

Kaufmann, William K.; Nevis, Kathleen R.; Qu, Pingping; Ibrahim, Joseph G.; Zhou, Tong; Zhou, Yingchun; Simpson, Dennis A.; Helms-Deaton, Jennifer; Cordeiro-Stone, Marila; Moore, Dominic T.; Thomas, Nancy E.; Hao, Honglin; Liu, Zhi; Shields, Janiel M.; Scott, Glynis A.; Sharpless, Norman E.

2009-01-01

Defects in DNA damage responses may underlie genetic instability and malignant progression in melanoma. Cultures of normal human melanocytes (NHMs) and melanoma lines were analyzed to determine whether global patterns of gene expression could predict the efficacy of DNA damage cell cycle checkpoints that arrest growth and suppress genetic instability. NHMs displayed effective G1 and G2 checkpoint responses to ionizing radiation-induced DNA damage. A majority of melanoma cell lines (11/16) displayed significant quantitative defects in one or both checkpoints. Melanomas with B-RAF mutations as a class displayed a significant defect in DNA damage G2 checkpoint function. In contrast the epithelial-like subtype of melanomas with wild-type N-RAS and B-RAF alleles displayed an effective G2 checkpoint but a significant defect in G1 checkpoint function. RNA expression profiling revealed that melanoma lines with defects in the DNA damage G1 checkpoint displayed reduced expression of p53 transcriptional targets, such as CDKN1A and DDB2, and enhanced expression of proliferation-associated genes, such as CDC7 and GEMININ. A Bayesian analysis tool was more accurate than significance analysis of microarrays for predicting checkpoint function using a leave-one-out method. The results suggest that defects in DNA damage checkpoints may be recognized in melanomas through analysis of gene expression. PMID:17597816

Expression of Histone Deacetylases in Cellular Compartments of the Mouse Brain and the Effects of Ischemia

PubMed Central

Bachleda, Amelia; Morrison, Richard S.; Murphy, Sean P.

2011-01-01

Drugs that inhibit specific histone deacetylase (HDAC) activities have enormous potential in preventing the consequences of acute injury to the nervous system and in allaying neurodegeneration. However, very little is known about the expression pattern of the HDACs in the central nervous system (CNS). Identifying the cell types that express HDACs in the CNS is important for determining therapeutic targets for HDAC inhibitors and evaluating potential side effects. We characterized the cellular expression of HDACs 1–3, and HDACs 4 and 6, in the adult mouse brain in the cingulate cortex, parietal cortex, dentate gyrus, and CA1 regions of the hippocampus and subcortical white matter. Expression of class I HDACs showed a cell-and region-specific pattern. Transient focal ischemia induced by temporary middle cerebral artery occlusion, or global ischemia induced by in vitro oxygen–glucose deprivation, altered the extent of HDAC expression in a region- and cell-specific manner. The pan-HDAC inhibitor, SAHA, reduced ischemia-induced alterations in HDACs. The results suggest that in addition to promoting epigenetic changes in transcriptional activity in the nucleus of neurons and glia, HDACs may also have non-transcriptional actions in axons and the distant processes of glial cells and may significantly modulate the response to injury in a cell- and region-specific manner. PMID:21966324

Spectral Biclustering of Microarray Data: Coclustering Genes and Conditions

PubMed Central

Kluger, Yuval; Basri, Ronen; Chang, Joseph T.; Gerstein, Mark

2003-01-01

Global analyses of RNA expression levels are useful for classifying genes and overall phenotypes. Often these classification problems are linked, and one wants to find “marker genes” that are differentially expressed in particular sets of “conditions.” We have developed a method that simultaneously clusters genes and conditions, finding distinctive “checkerboard” patterns in matrices of gene expression data, if they exist. In a cancer context, these checkerboards correspond to genes that are markedly up- or downregulated in patients with particular types of tumors. Our method, spectral biclustering, is based on the observation that checkerboard structures in matrices of expression data can be found in eigenvectors corresponding to characteristic expression patterns across genes or conditions. In addition, these eigenvectors can be readily identified by commonly used linear algebra approaches, in particular the singular value decomposition (SVD), coupled with closely integrated normalization steps. We present a number of variants of the approach, depending on whether the normalization over genes and conditions is done independently or in a coupled fashion. We then apply spectral biclustering to a selection of publicly available cancer expression data sets, and examine the degree to which the approach is able to identify checkerboard structures. Furthermore, we compare the performance of our biclustering methods against a number of reasonable benchmarks (e.g., direct application of SVD or normalized cuts to raw data). PMID:12671006

Mutations in TET2 and DNMT3A genes are associated with changes in global and gene-specific methylation in acute myeloid leukemia.

PubMed

Ponciano-Gómez, Alberto; Martínez-Tovar, Adolfo; Vela-Ojeda, Jorge; Olarte-Carrillo, Irma; Centeno-Cruz, Federico; Garrido, Efraín

2017-10-01

Acute myeloid leukemia is characterized by its high biological and clinical heterogeneity, which represents an important barrier for a precise disease classification and accurate therapy. While epigenetic aberrations play a pivotal role in acute myeloid leukemia pathophysiology, molecular signatures such as change in the DNA methylation patterns and genetic mutations in enzymes needed to the methylation process can also be helpful for classifying acute myeloid leukemia. Our study aims to unveil the relevance of DNMT3A and TET2 genes in global and specific methylation patterns in acute myeloid leukemia. Peripheral blood samples from 110 untreated patients with acute myeloid leukemia and 15 healthy control individuals were collected. Global 5-methylcytosine and 5-hydroxymethylcytosine in genomic DNA from peripheral blood leukocytes were measured by using the MethylFlashTM Quantification kits. DNMT3A and TET2 expression levels were evaluated by real-time quantitative polymerase chain reaction. The R882A hotspot of DNMT3A and exons 6-10 of TET2 were amplified by polymerase chain reaction and sequenced using the Sanger method. Methylation patterns of 16 gene promoters were evaluated by pyrosequencing after treating DNA with sodium bisulfite, and their transcriptional products were measured by real-time quantitative polymerase chain reaction.Here, we demonstrate altered levels of 5-methylcytosine and 5-hydroxymethylcytosine and highly variable transcript levels of DNMT3A and TET2 in peripheral blood leukocytes from acute myeloid leukemia patients. We found a mutation prevalence of 2.7% for DNMT3A and 11.8% for TET2 in the Mexican population with this disease. The average overall survival of acute myeloid leukemia patients with DNMT3A mutations was only 4 months. In addition, we showed that mutations in DNMT3A and TET2 may cause irregular DNA methylation patterns and transcriptional expression levels in 16 genes known to be involved in acute myeloid leukemia pathogenesis. Our findings suggest that alterations in DNMT3A and TET2 may be associated with acute myeloid leukemia prognosis. Furthermore, alterations in these enzymes affect normal methylation patterns in acute myeloid leukemia- specific genes, which in turn, may influence patient survival.

Endometriosis Is Characterized by a Distinct Pattern of Histone 3 and Histone 4 Lysine Modifications

PubMed Central

Monteiro, Janice B.; Colón-Díaz, Maricarmen; García, Miosotis; Gutierrez, Sylvia; Colón, Mariano; Seto, Edward; Laboy, Joaquín

2014-01-01

Background: The histone modification patterns in endometriosis have not been fully characterized. This gap in knowledge results in a poor understanding of the epigenetic mechanisms (and potential therapeutic targets) at play. We aimed to (1) assess global acetylation status of histone 3 (H3) and histone 4 (H4), (2) measure levels of H3 and H4 lysine (K) acetylation and methylation, and (3) to identify histone acetylation patterns in promoter regions of candidate genes in tissues from patients and controls. Methods: Global and K-specific acetylation/methylation levels of histones were measured in 24 lesions, 15 endometrium from patients, and 26 endometrium from controls. Chromatin immunoprecipitation (ChIP)–polymerase chain reaction was used to determine the histone acetylation status of the promoter regions of candidate genes in tissues. Results: The lesions were globally hypoacetylated at H3 (but not H4) compared to eutopic endometrium from controls. Lesions had significantly lower levels of H3K9ac and H4K16ac compared to eutopic endometrium from patients and controls. Tissues from patients were hypermethylated at H3K4, H3K9, and H3K27 compared to endometrium from controls. The ChIP analysis showed hypoacetylation of H3/H4 within promoter regions of candidate genes known to be downregulated in endometriosis (e.g., HOXA10, ESR1, CDH1, and p21WAF1/Cip1) in lesions versus control endometrium. The stereoidogenic factor 1 (SF1) promoter region was enriched for acetylated H3 and H4 in lesions versus control tissues, correlating with its reported high expression in lesions. Conclusions: This study describes the histone code of lesions and endometrium from patients with endometriosis and provides support for a possible role of histone modification in modulation of gene expression in endometriosis. PMID:23899551

Transcriptome analysis of salinity stress responses in common wheat using a 22k oligo-DNA microarray.

PubMed

Kawaura, Kanako; Mochida, Keiichi; Yamazaki, Yukiko; Ogihara, Yasunari

2006-04-01

In this study, we constructed a 22k wheat oligo-DNA microarray. A total of 148,676 expressed sequence tags of common wheat were collected from the database of the Wheat Genomics Consortium of Japan. These were grouped into 34,064 contigs, which were then used to design an oligonucleotide DNA microarray. Following a multistep selection of the sense strand, 21,939 60-mer oligo-DNA probes were selected for attachment on the microarray slide. This 22k oligo-DNA microarray was used to examine the transcriptional response of wheat to salt stress. More than 95% of the probes gave reproducible hybridization signals when targeted with RNAs extracted from salt-treated wheat shoots and roots. With the microarray, we identified 1,811 genes whose expressions changed more than 2-fold in response to salt. These included genes known to mediate response to salt, as well as unknown genes, and they were classified into 12 major groups by hierarchical clustering. These gene expression patterns were also confirmed by real-time reverse transcription-PCR. Many of the genes with unknown function were clustered together with genes known to be involved in response to salt stress. Thus, analysis of gene expression patterns combined with gene ontology should help identify the function of the unknown genes. Also, functional analysis of these wheat genes should provide new insight into the response to salt stress. Finally, these results indicate that the 22k oligo-DNA microarray is a reliable method for monitoring global gene expression patterns in wheat.

Diurnal Cycling Transcription Factors of Pineapple Revealed by Genome-Wide Annotation and Global Transcriptomic Analysis

PubMed Central

Sharma, Anupma; Wai, Ching Man; Ming, Ray

2017-01-01

Abstract Circadian clock provides fitness advantage by coordinating internal metabolic and physiological processes to external cyclic environments. Core clock components exhibit daily rhythmic changes in gene expression, and the majority of them are transcription factors (TFs) and transcription coregulators (TCs). We annotated 1,398 TFs from 67 TF families and 80 TCs from 20 TC families in pineapple, and analyzed their tissue-specific and diurnal expression patterns. Approximately 42% of TFs and 45% of TCs displayed diel rhythmic expression, including 177 TF/TCs cycling only in the nonphotosynthetic leaf tissue, 247 cycling only in the photosynthetic leaf tissue, and 201 cycling in both. We identified 68 TF/TCs whose cycling expression was tightly coupled between the photosynthetic and nonphotosynthetic leaf tissues. These TF/TCs likely coordinate key biological processes in pineapple as we demonstrated that this group is enriched in homologous genes that form the core circadian clock in Arabidopsis and includes a STOP1 homolog. Two lines of evidence support the important role of the STOP1 homolog in regulating CAM photosynthesis in pineapple. First, STOP1 responds to acidic pH and regulates a malate channel in multiple plant species. Second, the cycling expression pattern of the pineapple STOP1 and the diurnal pattern of malate accumulation in pineapple leaf are correlated. We further examined duplicate-gene retention and loss in major known circadian genes and refined their evolutionary relationships between pineapple and other plants. Significant variations in duplicate-gene retention and loss were observed for most clock genes in both monocots and dicots. PMID:28922793

DNA methyl transferases are differentially expressed in the human anterior eye segment.

PubMed

Bonnin, Nicolas; Belville, Corinne; Chiambaretta, Frédéric; Sapin, Vincent; Blanchon, Loïc

2014-08-01

DNA methylation is an epigenetic mark involved in the control of genes expression. Abnormal epigenetic events have been reported in human pathologies but weakly documented in eye diseases. The purpose of this study was to establish DNMT mRNA and protein expression levels in the anterior eye segment tissues and their related (primary or immortalized) cell cultures as a first step towards future in vivo and in vitro methylomic studies. Total mRNA was extracted from human cornea, conjunctiva, anterior lens capsule, trabeculum and related cell cultures (cornea epithelial, trabecular meshwork, keratocytes for primary cells; and HCE, Chang, B-3 for immortalized cells). cDNA was quantified by real-time PCR using specific primers for DNMT1, 2, 3A, 3B and 3L. Immunolocalization assays were carried out on human cornea using specific primary antibodies for DNMT1, 2 and 3A, 3B and 3L. All DNMT transcripts were detected in human cornea, conjunctiva, anterior lens capsule, trabeculum and related cells but showed statistically different expression patterns between tissues and cells. DNMT2 protein presented a specific and singular expression pattern in corneal endothelium. This study produced the first inventory of the expression patterns of DNMTs in human adult anterior eye segment. Our research highlights that DNA methylation cannot be ruled out as a way to bring new insights into well-known ocular diseases. In addition, future DNA methylation studies using various cells as experimental models need to be conducted with attention to approach the results analysis from a global tissue perspective. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Temporal components of the motor patterns expressed by the human spinal cord reflect foot kinematics.

PubMed

Ivanenko, Yuri P; Grasso, Renato; Zago, Myrka; Molinari, Marco; Scivoletto, Giorgio; Castellano, Vincenzo; Macellari, Velio; Lacquaniti, Francesco

2003-11-01

What are the building blocks with which the human spinal cord constructs the motor patterns of locomotion? In principle, they could correspond to each individual activity pattern in dozens of different muscles. Alternatively, there could exist a small set of constituent temporal components that are common to all activation patterns and reflect global kinematic goals. To address this issue, we studied patients with spinal injury trained to step on a treadmill with body weight support. Patients learned to produce foot kinematics similar to that of healthy subjects but with activity patterns of individual muscles generally different from the control group. Hidden in the muscle patterns, we found a basic set of five temporal components, whose flexible combination accounted for the wide range of muscle patterns recorded in both controls and patients. Furthermore, two of the components were systematically related to foot kinematics across different stepping speeds and loading conditions. We suggest that the components are related to control signals output by spinal pattern generators, normally under the influence of descending and afferent inputs.

Impact of 5-aza-2'-deoxycytidine and epigallocatechin-3-gallate for induction of human regulatory T cells.

PubMed

Kehrmann, Jan; Tatura, Roman; Zeschnigk, Michael; Probst-Kepper, Michael; Geffers, Robert; Steinmann, Joerg; Buer, Jan

2014-07-01

The epigenetic regulation of transcription factor genes is critical for T-cell lineage specification. A specific methylation pattern within a conserved region of the lineage specifying transcription factor gene FOXP3, the Treg-specific demethylated region (TSDR), is restricted to regulatory T (Treg) cells and is required for stable expression of FOXP3 and suppressive function. We analysed the impact of hypomethylating agents 5-aza-2'-deoxycytidine and epigallocatechin-3-gallate on human CD4(+)  CD25(-) T cells for generating demethylation within FOXP3-TSDR and inducing functional Treg cells. Gene expression, including lineage-specifying transcription factors of the major T-cell lineages and their leading cytokines, functional properties and global transcriptome changes were analysed. The FOXP3-TSDR methylation pattern was determined by using deep amplicon bisulphite sequencing. 5-aza-2'-deoxycytidine induced FOXP3-TSDR hypomethylation and expression of the Treg-cell-specific genes FOXP3 and LRRC32. Proliferation of 5-aza-2'-deoxycytidine-treated cells was reduced, but the cells did not show suppressive function. Hypomethylation was not restricted to FOXP3-TSDR and expression of master transcription factors and leading cytokines of T helper type 1 and type 17 cells were induced. Epigallocatechin-3-gallate induced global DNA hypomethylation to a lesser extent than 5-aza-2'-deoxycitidine, but no relevant hypomethylation within FOXP3-TSDR or expression of Treg-cell-specific genes. Neither of the DNA methyltransferase inhibitors induced fully functional human Treg cells. 5-aza-2'-deoxycitidine-treated cells resembled Treg cells, but they did not suppress proliferation of responder cells, which is an essential capability to be used for Treg cell transfer therapy. Using a recently developed targeted demethylation technology might be a more promising approach for the generation of functional Treg cells. © 2014 John Wiley & Sons Ltd.

Exploratory Investigation of Bacteroides fragilis Transcriptional Response during In vitro Exposure to Subinhibitory Concentration of Metronidazole

PubMed Central

de Freitas, Michele C. R.; Resende, Juliana A.; Ferreira-Machado, Alessandra B.; Saji, Guadalupe D. R. Q.; de Vasconcelos, Ana T. R.; da Silva, Vânia L.; Nicolás, Marisa F.; Diniz, Cláudio G.

2016-01-01

Bacteroides fragilis, member from commensal gut microbiota, is an important pathogen associated to endogenous infections and metronidazole remains a valuable antibiotic for the treatment of these infections, although bacterial resistance is widely reported. Considering the need of a better understanding on the global mechanisms by which B. fragilis survive upon metronidazole exposure, we performed a RNA-seq transcriptomic approach with validation of gene expression results by qPCR. Bacteria strains were selected after in vitro subcultures with subinhibitory concentration (SIC) of the drug. From a wild type B. fragilis ATCC 43859 four derivative strains were selected: first and fourth subcultures under metronidazole exposure and first and fourth subcultures after drug removal. According to global gene expression analysis, 2,146 protein coding genes were identified, of which a total of 1,618 (77%) were assigned to a Gene Ontology term (GO), indicating that most known cellular functions were taken. Among these 2,146 protein coding genes, 377 were shared among all strains, suggesting that they are critical for B. fragilis survival. In order to identify distinct expression patterns, we also performed a K-means clustering analysis set to 15 groups. This analysis allowed us to detect the major activated or repressed genes encoding for enzymes which act in several metabolic pathways involved in metronidazole response such as drug activation, defense mechanisms against superoxide ions, high expression level of multidrug efflux pumps, and DNA repair. The strains collected after metronidazole removal were functionally more similar to those cultured under drug pressure, reinforcing that drug-exposure lead to drastic persistent changes in the B. fragilis gene expression patterns. These results may help to elucidate B. fragilis response during metronidazole exposure, mainly at SIC, contributing with information about bacterial survival strategies under stress conditions in their environment. PMID:27703449

The global response of Nostoc punctiforme ATCC 29133 to UVA stress, assessed in a temporal DNA microarray study.

PubMed

Soule, Tanya; Gao, Qunjie; Stout, Valerie; Garcia-Pichel, Ferran

2013-01-01

Cyanobacteria in nature are exposed not only to the visible spectrum of sunlight but also to its harmful ultraviolet components (UVA and UVB). We used Nostoc punctiforme ATCC 29133 as a model to study the UVA response by analyzing global gene expression patterns using genomic microarrays. UVA exposure resulted in the statistically detectable differential expression of 573 genes of the 6903 that were probed, compared with that of the control cultures. Of those genes, 473 were up-regulated, while only 100 were down-regulated. Many of the down-regulated genes were involved in photosynthetic pigment biosynthesis, indicating a significant shift in this metabolism. As expected, we detected the up-regulation of genes encoding antioxidant enzymes and the sunscreen, scytonemin. However, a majority of the up-regulated genes, 47%, were unassignable bioinformatically to known functional categories, suggesting that the UVA stress response is not well understood. Interestingly, the most dramatic up-regulation involved several contiguous genes of unassigned metabolism on plasmid A. This is the first global UVA stress response analysis of any phototrophic microorganism and the differential expression of 8% of the genes of the Nostoc genome indicates that adaptation to UVA in Nostoc has been an evolutionary force of significance. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Welcome, Michael L.; Bell, Christian S.

GASNet (Global-Address Space Networking) is a language-independent, low-level networking layer that provides network-independent, high-performance communication primitives tailored for implementing parallel global address space SPMD languages such as UPC and Titanium. The interface is primarily intended as a compilation target and for use by runtime library writers (as opposed to end users), and the primary goals are high performance, interface portability, and expressiveness. GASNet is designed specifically to support high-performance, portable implementations of global address space languages on modern high-end communication networks. The interface provides the flexibility and extensibility required to express a wide variety of communication patterns without sacrificing performancemore » by imposing large computational overheads in the interface. The design of the GASNet interface is partitioned into two layers to maximize porting ease without sacrificing performance: the lower level is a narrow but very general interface called the GASNet core API - the design is basedheavily on Active Messages, and is implemented directly on top of each individual network architecture. The upper level is a wider and more expressive interface called GASNet extended API, which provides high-level operations such as remote memory access and various collective operations. This release implements GASNet over MPI, the Quadrics "elan" API, the Myrinet "GM" API and the "LAPI" interface to the IBM SP switch. A template is provided for adding support for additional network interfaces.« less

Comprehensive analysis and discovery of drought-related NAC transcription factors in common bean.

PubMed

Wu, Jing; Wang, Lanfen; Wang, Shumin

2016-09-07

Common bean (Phaseolus vulgaris L.) is an important warm-season food legume. Drought is the most important environmental stress factor affecting large areas of common bean via plant death or reduced global production. The NAM, ATAF1/2 and CUC2 (NAC) domain protein family are classic transcription factors (TFs) involved in a variety of abiotic stresses, particularly drought stress. However, the NAC TFs in common bean have not been characterized. In the present study, 86 putative NAC TF proteins were identified from the common bean genome database and located on 11 common bean chromosomes. The proteins were phylogenetically clustered into 8 distinct subfamilies. The gene structure and motif composition of common bean NACs were similar in each subfamily. These results suggest that NACs in the same subfamily may possess conserved functions. The expression patterns of common bean NAC genes were also characterized. The majority of NACs exhibited specific temporal and spatial expression patterns. We identified 22 drought-related NAC TFs based on transcriptome data for drought-tolerant and drought-sensitive genotypes. Quantitative real-time PCR (qRT-PCR) was performed to confirm the expression patterns of the 20 drought-related NAC genes. Based on the common bean genome sequence, we analyzed the structural characteristics, genome distribution, and expression profiles of NAC gene family members and analyzed drought-responsive NAC genes. Our results provide useful information for the functional characterization of common bean NAC genes and rich resources and opportunities for understanding common bean drought stress tolerance mechanisms.

Genome-wide classification, evolutionary analysis and gene expression patterns of the kinome in Gossypium

PubMed Central

Yan, Jun; Li, Guilin; Guo, Xingqi; Li, Yang; Cao, Xuecheng

2018-01-01

The protein kinase (PK, kinome) family is one of the largest families in plants and regulates almost all aspects of plant processes, including plant development and stress responses. Despite their important functions, comprehensive functional classification, evolutionary analysis and expression patterns of the cotton PK gene family has yet to be performed on PK genes. In this study, we identified the cotton kinomes in the Gossypium raimondii, Gossypium arboretum, Gossypium hirsutum and Gossypium barbadense genomes and classified them into 7 groups and 122–24 subfamilies using software HMMER v3.0 scanning and neighbor-joining (NJ) phylogenetic analysis. Some conserved exon-intron structures were identified not only in cotton species but also in primitive plants, ferns and moss, suggesting the significant function and ancient origination of these PK genes. Collinearity analysis revealed that 16.6 million years ago (Mya) cotton-specific whole genome duplication (WGD) events may have played a partial role in the expansion of the cotton kinomes, whereas tandem duplication (TD) events mainly contributed to the expansion of the cotton RLK group. Synteny analysis revealed that tetraploidization of G. hirsutum and G. barbadense contributed to the expansion of G. hirsutum and G. barbadense PKs. Global expression analysis of cotton PKs revealed stress-specific and fiber development-related expression patterns, suggesting that many cotton PKs might be involved in the regulation of the stress response and fiber development processes. This study provides foundational information for further studies on the evolution and molecular function of cotton PKs. PMID:29768506

Muscle-specific gene expression is underscored by differential stressor responses and coexpression changes.

PubMed

Moreno-Sánchez, Natalia; Rueda, Julia; Reverter, Antonio; Carabaño, María Jesús; Díaz, Clara

2012-03-01

Variations on the transcriptome from one skeletal muscle type to another still remain unknown. The reliable identification of stable gene coexpression networks is essential to unravel gene functions and define biological processes. The differential expression of two distinct muscles, M. flexor digitorum (FD) and M. psoas major (PM), was studied using microarrays in cattle to illustrate muscle-specific transcription patterns and to quantify changes in connectivity regarding the expected gene coexpression pattern. A total of 206 genes were differentially expressed (DE), 94 upregulated in PM and 112 in FD. The distribution of DE genes in pathways and biological functions was explored in the context of system biology. Global interactomes for genes of interest were predicted. Fast/slow twitch genes, genes coding for extracellular matrix, ribosomal and heat shock proteins, and fatty acid uptake centred the specific gene expression patterns per muscle. Genes involved in repairing mechanisms, such as ribosomal and heat shock proteins, suggested a differential ability of muscles to react to similar stressing factors, acting preferentially in slow twitch muscles. Muscle attributes do not seem to be completely explained by the muscle fibre composition. Changes in connectivity accounted for 24% of significant correlations between DE genes. Genes changing their connectivity mostly seem to contribute to the main differential attributes that characterize each specific muscle type. These results underscore the unique flexibility of skeletal muscle where a substantial set of genes are able to change their behavior depending on the circumstances.

MYCN controls an alternative RNA splicing program in high-risk metastatic neuroblastoma

PubMed Central

Zhang, Shile; Wei, Jun S.; Li, Samuel Q.; Badgett, Tom C.; Song, Young K.; Agarwal, Saurabh; Coarfa, Cristian; Tolman, Catherine; Hurd, Laura; Liao, Hongling; He, Jianbin; Wen, Xinyu; Liu, Zhihui; Thiele, Carol J.; Westermann, Frank; Asgharzadeh, Shahab; Seeger, Robert C.; Maris, John M.; Auvil, Jamie M Guidry; Smith, Malcolm A; Kolaczyk, Eric D; Shohet, Jason; Khan, Javed

2016-01-01

The molecular mechanisms underlying the aggressive behavior of MYCN driven neuroblastoma (NBL) is under intense investigation; however, little is known about the impact of this family of transcription factors on the splicing program. Here we used high-throughput RNA sequencing to systematically study the expression of RNA isoforms in stage 4 MYCN-amplified NBL, an aggressive subtype of metastatic NBL. We show that MYCN-amplified NBL tumors display a distinct gene splicing pattern affecting multiple cancer hallmark functions. Six splicing factors displayed unique differential expression patterns in MYCN-amplified tumors and cell lines, and the binding motifs for some of these splicing factors are significantly enriched in differentially-spliced genes. Direct binding of MYCN to promoter regions of the splicing factors PTBP1 and HNRNPA1 detected by ChIP-seq demonstrates MYCN controls the splicing pattern by direct regulation of the expression of these key splicing factors. Furthermore, high expression of PTBP1 and HNRNPA1 was significantly associated with poor overall survival of stage4 NBL patients (p≤0.05). Knocking down PTBP1, HNRNPA1 and their downstream target PKM2, an isoform of pro-tumor-growth, result in repressed growth of NBL cells. Therefore, our study reveals a novel role of MYCN in controlling global splicing program through regulation of splicing factors in addition to its well-known role in the transcription program. These findings suggest a therapeutically potential to target the key splicing factors or gene isoforms in high-risk NBL with MYCN-amplification. PMID:26683771

Global Regulatory Pathways in the Alphaproteobacteria

DOE Office of Scientific and Technical Information (OSTI.GOV)

none

A major goal for microbiologists in the twenty-first century is to develop an understanding of the microbial cell in all its complexity. In addition to understanding the function of individual gene products we need to focus on how the cell regulates gene expression at a global level to respond to different environmental parameters. Development of genomic technologies such as complete genome sequencing, proteomics, and global comparisons of mRNA expression patterns allows us to begin to address this issue. This proposal focuses on a number of phylogenetically related bacteria that are involved in environmentally important processes such as carbon sequestration andmore » bioremediation. Genome sequencing projects of a number of these bacteria have revealed the presence of a small family of regulatory genes found thus far only in the alpha-proteobacteria. These genes encode proteins that are related to the global regulatory protein RosR in Rhizobium etli, which is involved in determining nodulation competitiveness in this bacterium. Our goal is to examine the function of the proteins encoded by this gene family in several of the bacteria containing homologs to RosR. We will construct gene disruption mutations in a number of these bacteria and characterize the resulting mutant strains using two-dimensional gel electrophoresis and genetic and biochemical techniques. We will thus determine if the other proteins also function as global regulators of gene expression. Using proteomics methods we will identify the specific proteins whose expression varies depending on the presence or absence of the RosR homolog. Over fifty loci regulated by RosR have been identified in R. etli using transposon mutagenesis; this will serve as out benchmark to which we will compare the other regulons. We expect to identify genes regulated by RosR homologs in several bacterial species, including, but not limited to Rhodopseudomonas palustris and Sphingomonas aromaticivorans. In this way we will provide valuable information on gene regulation in this group of bacteria, expand our understanding of the evolution of global regulatory pathways, and develop methods for comparative regulon analysis among microbes.« less

The body electric 2.0: recent advances in developmental bioelectricity for regenerative and synthetic bioengineering.

PubMed

Mathews, Juanita; Levin, Michael

2018-04-20

Breakthroughs in biomedicine and synthetic bioengineering require predictive, rational control over anatomical structure and function. Recent successes in manipulating cellular and molecular hardware have not been matched by progress in understanding the patterning software implemented during embryogenesis and regeneration. A fundamental capability gap is driving desired changes in growth and form to address birth defects and traumatic injury. Here we review new tools, results, and conceptual advances in an exciting emerging field: endogenous non-neural bioelectric signaling, which enables cellular collectives to make global decisions and implement large-scale pattern homeostasis. Spatially distributed electric circuits regulate gene expression, organ morphogenesis, and body-wide axial patterning. Developmental bioelectricity facilitates the interface to organ-level modular control points that direct patterning in vivo. Cracking the bioelectric code will enable transformative progress in bioengineering and regenerative medicine. Copyright © 2018 Elsevier Ltd. All rights reserved.

The developmental transcriptome atlas of the spoon worm Urechis unicinctus (Echiurida: Annelida).

PubMed

Park, Chungoo; Han, Yong-Hee; Lee, Sung-Gwon; Ry, Kyoung-Bin; Oh, Jooseong; Kern, Elizabeth M A; Park, Joong-Ki; Cho, Sung-Jin

2018-03-01

Echiurida is one of the most intriguing major subgroups of annelida because, unlike most other annelids, echiurids lack metameric body segmentation as adults. For this reason, transcriptome analyses from various developmental stages of echiurid species can be of substantial value for understanding precise expression levels and the complex regulatory networks during early and larval development. A total of 914 million raw RNA-Seq reads were produced from 14 developmental stages of Urechis unicinctus and were de novo assembled into contigs spanning 63,928,225 bp with an N50 length of 2700 bp. The resulting comprehensive transcriptome database of the early developmental stages of U. unicinctus consists of 20,305 representative functional protein-coding transcripts. Approximately 66% of unigenes were assigned to superphylum-level taxa, including Lophotrochozoa (40%). The completeness of the transcriptome assembly was assessed using benchmarking universal single-copy orthologs; 75.7% of the single-copy orthologs were presented in our transcriptome database. We observed 3 distinct patterns of global transcriptome profiles from 14 developmental stages and identified 12,705 genes that showed dynamic regulation patterns during the differentiation and maturation of U. unicinctus cells. We present the first large-scale developmental transcriptome dataset of U. unicinctus and provide a general overview of the dynamics of global gene expression changes during its early developmental stages. The analysis of time-course gene expression data is a first step toward understanding the complex developmental gene regulatory networks in U. unicinctus and will furnish a valuable resource for analyzing the functions of gene repertoires in various developmental phases.

Constitutional trisomy 8 mosaicism as a model for epigenetic studies of aneuploidy

PubMed Central

2013-01-01

Background To investigate epigenetic patterns associated with aneuploidy we used constitutional trisomy 8 mosaicism (CT8M) as a model, enabling analyses of single cell clones, harboring either trisomy or disomy 8, from the same patient; this circumvents any bias introduced by using cells from unrelated, healthy individuals as controls. We profiled gene and miRNA expression as well as genome-wide and promoter specific DNA methylation and hydroxymethylation patterns in trisomic and disomic fibroblasts, using microarrays and methylated DNA immunoprecipitation. Results Trisomy 8-positive fibroblasts displayed a characteristic expression and methylation phenotype distinct from disomic fibroblasts, with the majority (65%) of chromosome 8 genes in the trisomic cells being overexpressed. However, 69% of all deregulated genes and non-coding RNAs were not located on this chromosome. Pathway analysis of the deregulated genes revealed that cancer, genetic disorder, and hematopoiesis were top ranked. The trisomy 8-positive cells displayed depletion of 5-hydroxymethylcytosine and global hypomethylation of gene-poor regions on chromosome 8, thus partly mimicking the inactivated X chromosome in females. Conclusions Trisomy 8 affects genes situated also on other chromosomes which, in cooperation with the observed chromosome 8 gene dosage effect, has an impact on the clinical features of CT8M, as demonstrated by the pathway analysis revealing key features that might explain the increased incidence of hematologic malignancies in CT8M patients. Furthermore, we hypothesize that the general depletion of hydroxymethylation and global hypomethylation of chromosome 8 may be unrelated to gene expression regulation, instead being associated with a general mechanism of chromatin processing and compartmentalization of additional chromosomes. PMID:23816241

Variability of esterase patterns in adult flies of the saltans species group of Drosophila (subgenus Sophophora).

PubMed

Bernardo, Alessandra Augusta; Bicudo, Hermione Elly Melara de Campos

2009-09-01

Esterases are known for their involvement in several physiological processes and high degree of polymorphism, in many organisms. Such polymorphism has been used to characterize species and species groups and to study genetic changes occurred in their evolutionary history. In the present study, the esterase patterns of 19 strains from 10 species representative of the five subgroups of the saltans species group were analyzed using polyacrylamide gel electrophoresis and alpha- and beta- naphthyl acetates as substrates. Fifty-one esterase bands were detected and classified as 31 alpha-esterases, 18 beta-esterases and two alpha/beta-esterases. On the basis of the inhibition patterns using Malathion and eserine sulfate, 34 bands were classified as carboxylesterases, 14 as acethylesterases and three as cholinesterases. Ten gene loci were tentatively established on the basis of data on band position in the gel, substrate preference and inhibition pattern. Twenty bands were species-specific, the remaining being shared by species from the same or different subgroups. Bands detected exclusively in males and bands with a different frequency or degree of expression between sexes were also detected. In the gels prepared for analysis of gene expression in the body parts (head, thorax and abdomen), the degree of expression of the beta-esterases was higher in the thorax, while the alpha-esterases were expressed predominantly in the abdomen and thorax. A global view of the data available at present on the esterases of the species from the saltans group and their degree of polymorphism are presented, as well as the possibility of using some beta-esterases, because of their characteristics in the gels, as markers for species identification.

Towards understanding the breast cancer epigenome: a comparison of genome-wide DNA methylation and gene expression data

PubMed Central

Michiels, Stefan; Metzger-Filho, Otto; Saini, Kamal S.

2016-01-01

Until recently, an elevated disease risk has been ascribed to a genetic predisposition, however, exciting progress over the past years has discovered alternate elements of inheritance that involve epigenetic regulation. Epigenetic changes are heritably stable alterations that include DNA methylation, histone modifications and RNA-mediated silencing. Aberrant DNA methylation is a common molecular basis for a number of important human diseases, including breast cancer. Changes in DNA methylation profoundly affect global gene expression patterns. What is emerging is a more dynamic and complex association between DNA methylation and gene expression than previously believed. Although many tools have already been developed for analyzing genome-wide gene expression data, tools for analyzing genome-wide DNA methylation have not yet reached the same level of refinement. Here we provide an in-depth analysis of DNA methylation in parallel with gene expression data characteristics and describe the particularities of low-level and high-level analyses of DNA methylation data. Low-level analysis refers to pre-processing of methylation data (i.e. normalization, transformation and filtering), whereas high-level analysis is focused on illustrating the application of the widely used class comparison, class prediction and class discovery methods to DNA methylation data. Furthermore, we investigate the influence of DNA methylation on gene expression by measuring the correlation between the degree of CpG methylation and the level of expression and to explore the pattern of methylation as a function of the promoter region. PMID:26657508

Towards understanding the breast cancer epigenome: a comparison of genome-wide DNA methylation and gene expression data.

PubMed

Singhal, Sandeep K; Usmani, Nawaid; Michiels, Stefan; Metzger-Filho, Otto; Saini, Kamal S; Kovalchuk, Olga; Parliament, Matthew

2016-01-19

Until recently, an elevated disease risk has been ascribed to a genetic predisposition, however, exciting progress over the past years has discovered alternate elements of inheritance that involve epigenetic regulation. Epigenetic changes are heritably stable alterations that include DNA methylation, histone modifications and RNA-mediated silencing. Aberrant DNA methylation is a common molecular basis for a number of important human diseases, including breast cancer. Changes in DNA methylation profoundly affect global gene expression patterns. What is emerging is a more dynamic and complex association between DNA methylation and gene expression than previously believed. Although many tools have already been developed for analyzing genome-wide gene expression data, tools for analyzing genome-wide DNA methylation have not yet reached the same level of refinement. Here we provide an in-depth analysis of DNA methylation in parallel with gene expression data characteristics and describe the particularities of low-level and high-level analyses of DNA methylation data. Low-level analysis refers to pre-processing of methylation data (i.e. normalization, transformation and filtering), whereas high-level analysis is focused on illustrating the application of the widely used class comparison, class prediction and class discovery methods to DNA methylation data. Furthermore, we investigate the influence of DNA methylation on gene expression by measuring the correlation between the degree of CpG methylation and the level of expression and to explore the pattern of methylation as a function of the promoter region.

The SLE transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non-coding and coding RNAs.

PubMed

Shi, Lihua; Zhang, Zhe; Yu, Angela M; Wang, Wei; Wei, Zhi; Akhter, Ehtisham; Maurer, Kelly; Costa Reis, Patrícia; Song, Li; Petri, Michelle; Sullivan, Kathleen E

2014-01-01

Gene expression studies of peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE) have demonstrated a type I interferon signature and increased expression of inflammatory cytokine genes. Studies of patients with Aicardi Goutières syndrome, commonly cited as a single gene model for SLE, have suggested that accumulation of non-coding RNAs may drive some of the pathologic gene expression, however, no RNA sequencing studies of SLE patients have been performed. This study was designed to define altered expression of coding and non-coding RNAs and to detect globally altered RNA processing in SLE. Purified monocytes from eight healthy age/gender matched controls and nine SLE patients (with low-moderate disease activity and lack of biologic drug use or immune suppressive treatment) were studied using RNA-seq. Quantitative RT-PCR was used to validate findings. Serum levels of endotoxin were measured by ELISA. We found that SLE patients had diminished expression of most endogenous retroviruses and small nucleolar RNAs, but exhibited increased expression of pri-miRNAs. Splicing patterns and polyadenylation were significantly altered. In addition, SLE monocytes expressed novel transcripts, an effect that was replicated by LPS treatment of control monocytes. We further identified increased circulating endotoxin in SLE patients. Monocytes from SLE patients exhibit globally dysregulated gene expression. The transcriptome is not simply altered by the transcriptional activation of a set of genes, but is qualitatively different in SLE. The identification of novel loci, inducible by LPS, suggests that chronic microbial translocation could contribute to the immunologic dysregulation in SLE, a new potential disease mechanism.

A novel X-linked disorder with developmental delay and autistic features.

PubMed

Kaya, Namik; Colak, Dilek; Albakheet, Albandary; Al-Owain, Mohammad; Abu-Dheim, Nada; Al-Younes, Banan; Al-Zahrani, Jawaher; Mukaddes, Nahit M; Dervent, Aysin; Al-Dosari, Naji; Al-Odaib, Ali; Kayaalp, Inci V; Al-Sayed, Moeenaladin; Al-Hassnan, Zuhair; Nester, Michael J; Al-Dosari, Mohammad; Al-Dhalaan, Hesham; Chedrawi, Aziza; Gunoz, Hulya; Karakas, Bedri; Sakati, Nadia; Alkuraya, Fowzan S; Gascon, Generaso G; Ozand, Pinar T

2012-04-01

Genomic duplications that lead to autism and other human diseases are interesting pathological lesions since the underlying mechanism almost certainly involves dosage sensitive genes. We aim to understand a novel genomic disorder with profound phenotypic consequences, most notably global developmental delay, autism, psychosis, and anorexia nervosa. We evaluated the affected individuals, all maternally related, using childhood autism rating scale (CARS) and Vineland Adaptive scales, magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) brain, electroencephalography (EEG), electromyography (EMG), muscle biopsy, high-resolution molecular karyotype arrays, Giemsa banding (G-banding) and fluorescent in situ hybridization (FISH) experiments, mitochondrial DNA (mtDNA) sequencing, X-chromosome inactivation study, global gene expression analysis on Epstein-Barr virus (EBV)-transformed lymphoblasts, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). We have identified a novel Xq12-q13.3 duplication in an extended family. Clinically normal mothers were completely skewed in favor of the normal chromosome X. Global transcriptional profiling of affected individuals and controls revealed significant alterations of genes and pathways in a pattern consistent with previous microarray studies of autism spectrum disorder patients. Moreover, expression analysis revealed copy number-dependent increased messenger RNA (mRNA) levels in affected patients compared to control individuals. A subset of differentially expressed genes was validated using qRT-PCR. Xq12-q13.3 duplication is a novel global developmental delay and autism-predisposing chromosomal aberration; pathogenesis of which may be mediated by increased dosage of genes contained in the duplication, including NLGN3, OPHN1, AR, EFNB1, TAF1, GJB1, and MED12. Copyright © 2011 American Neurological Association.

AAV-PHP.B-Mediated Global-Scale Expression in the Mouse Nervous System Enables GBA1 Gene Therapy for Wide Protection from Synucleinopathy.

PubMed

Morabito, Giuseppe; Giannelli, Serena G; Ordazzo, Gabriele; Bido, Simone; Castoldi, Valerio; Indrigo, Marzia; Cabassi, Tommaso; Cattaneo, Stefano; Luoni, Mirko; Cancellieri, Cinzia; Sessa, Alessandro; Bacigaluppi, Marco; Taverna, Stefano; Leocani, Letizia; Lanciego, José L; Broccoli, Vania

2017-12-06

The lack of technology for direct global-scale targeting of the adult mouse nervous system has hindered research on brain processing and dysfunctions. Currently, gene transfer is normally achieved by intraparenchymal viral injections, but these injections target a restricted brain area. Herein, we demonstrated that intravenous delivery of adeno-associated virus (AAV)-PHP.B viral particles permeated and diffused throughout the neural parenchyma, targeting both the central and the peripheral nervous system in a global pattern. We then established multiple procedures of viral transduction to control gene expression or inactivate gene function exclusively in the adult nervous system and assessed the underlying behavioral effects. Building on these results, we established an effective gene therapy strategy to counteract the widespread accumulation of α-synuclein deposits throughout the forebrain in a mouse model of synucleinopathy. Transduction of A53T-SCNA transgenic mice with AAV-PHP.B-GBA1 restored physiological levels of the enzyme, reduced α-synuclein pathology, and produced significant behavioral recovery. Finally, we provided evidence that AAV-PHP.B brain penetration does not lead to evident dysfunctions in blood-brain barrier integrity or permeability. Altogether, the AAV-PHP.B viral platform enables non-invasive, widespread, and long-lasting global neural expression of therapeutic genes, such as GBA1, providing an invaluable approach to treat neurodegenerative diseases with diffuse brain pathology such as synucleinopathies. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

An integrated genomics analysis of epigenetic subtypes in human breast tumors links DNA methylation patterns to chromatin states in normal mammary cells.

PubMed

Holm, Karolina; Staaf, Johan; Lauss, Martin; Aine, Mattias; Lindgren, David; Bendahl, Pär-Ola; Vallon-Christersson, Johan; Barkardottir, Rosa Bjork; Höglund, Mattias; Borg, Åke; Jönsson, Göran; Ringnér, Markus

2016-02-29

Aberrant DNA methylation is frequently observed in breast cancer. However, the relationship between methylation patterns and the heterogeneity of breast cancer has not been comprehensively characterized. Whole-genome DNA methylation analysis using Illumina Infinium HumanMethylation450 BeadChip arrays was performed on 188 human breast tumors. Unsupervised bootstrap consensus clustering was performed to identify DNA methylation epigenetic subgroups (epitypes). The Cancer Genome Atlas data, including methylation profiles of 669 human breast tumors, was used for validation. The identified epitypes were characterized by integration with publicly available genome-wide data, including gene expression levels, DNA copy numbers, whole-exome sequencing data, and chromatin states. We identified seven breast cancer epitypes. One epitype was distinctly associated with basal-like tumors and with BRCA1 mutations, one epitype contained a subset of ERBB2-amplified tumors characterized by multiple additional amplifications and the most complex genomes, and one epitype displayed a methylation profile similar to normal epithelial cells. Luminal tumors were stratified into the remaining four epitypes, with differences in promoter hypermethylation, global hypomethylation, proliferative rates, and genomic instability. Specific hyper- and hypomethylation across the basal-like epitype was rare. However, we observed that the candidate genomic instability drivers BRCA1 and HORMAD1 displayed aberrant methylation linked to gene expression levels in some basal-like tumors. Hypomethylation in luminal tumors was associated with DNA repeats and subtelomeric regions. We observed two dominant patterns of aberrant methylation in breast cancer. One pattern, constitutively methylated in both basal-like and luminal breast cancer, was linked to genes with promoters in a Polycomb-repressed state in normal epithelial cells and displayed no correlation with gene expression levels. The second pattern correlated with gene expression levels and was associated with methylation in luminal tumors and genes with active promoters in normal epithelial cells. Our results suggest that hypermethylation patterns across basal-like breast cancer may have limited influence on tumor progression and instead reflect the repressed chromatin state of the tissue of origin. On the contrary, hypermethylation patterns specific to luminal breast cancer influence gene expression, may contribute to tumor progression, and may present an actionable epigenetic alteration in a subset of luminal breast cancers.

Global population-specific variation in miRNA associated with cancer risk and clinical biomarkers.

PubMed

Rawlings-Goss, Renata A; Campbell, Michael C; Tishkoff, Sarah A

2014-08-28

MiRNA expression profiling is being actively investigated as a clinical biomarker and diagnostic tool to detect multiple cancer types and stages as well as other complex diseases. Initial investigations, however, have not comprehensively taken into account genetic variability affecting miRNA expression and/or function in populations of different ethnic backgrounds. Therefore, more complete surveys of miRNA genetic variability are needed to assess global patterns of miRNA variation within and between diverse human populations and their effect on clinically relevant miRNA genes. Genetic variation in 1524 miRNA genes was examined using whole genome sequencing (60x coverage) in a panel of 69 unrelated individuals from 14 global populations, including European, Asian and African populations. We identified 33 previously undescribed miRNA variants, and 31 miRNA containing variants that are globally population-differentiated in frequency between African and non-African populations (PD-miRNA). The top 1% of PD-miRNA were significantly enriched for regulation of genes involved in glucose/insulin metabolism and cell division (p < 10(-7)), most significantly the mitosis pathway, which is strongly linked to cancer onset. Overall, we identify 7 PD-miRNAs that are currently implicated as cancer biomarkers or diagnostics: hsa-mir-202, hsa-mir-423, hsa-mir-196a-2, hsa-mir-520h, hsa-mir-647, hsa-mir-943, and hsa-mir-1908. Notably, hsa-mir-202, a potential breast cancer biomarker, was found to show significantly high allele frequency differentiation at SNP rs12355840, which is known to affect miRNA expression levels in vivo and subsequently breast cancer mortality. MiRNA expression profiles represent a promising new category of disease biomarkers. However, population specific genetic variation can affect the prevalence and baseline expression of these miRNAs in diverse populations. Consequently, miRNA genetic and expression level variation among ethnic groups may be contributing in part to health disparities observed in multiple forms of cancer, specifically breast cancer, and will be an essential consideration when assessing the utility of miRNA biomarkers for the clinic.

Global proteomic analysis of two tick-borne emerging zoonotic agents: Anaplasma phagocytophilum and Ehrlichia chaffeensis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Mingqun ..; Kikuchi, Takane; Brewer, Heather M.

2011-02-17

Anaplasma phagocytophilum and Ehrlichia chaffeensis are obligatory intracellular {alpha}-proteobacteria that infect human leukocytes and cause potentially fatal emerging zoonoses. In the present study, we determined global protein expression profiles of these bacteria cultured in the human promyelocytic leukemia cell line, HL-60. Mass spectrometric (MS) analyses identified a total of 1,212 A. phagocytophilum and 1,021 E. chaffeensis proteins, representing 89.3 and 92.3% of the predicted bacterial proteomes, respectively. Nearly all bacterial proteins ({approx}99%) with known functions were expressed, whereas only approximately 80% of hypothetical proteins were detected in infected human cells. Quantitative MS/MS analyses indicated that highly expressed proteins in bothmore » bacteria included chaperones, enzymes involved in biosynthesis and metabolism, and outer membrane proteins, such as A. phagocytophilum P44 and E. chaffeensis P28/OMP-1. Among 113 A. phagocytophilum p44 paralogous genes, 110 of them were expressed and 88 of them were encoded by pseudogenes. In addition, bacterial infection of HL-60 cells up-regulated the expression of human proteins involved mostly in cytoskeleton components, vesicular trafficking, cell signaling, and energy metabolism, but down regulated some pattern recognition receptors involved in innate immunity. Our proteomics data represent a comprehensive analysis of A. phagocytophilum and E. chaffeensis proteomes, and provide a quantitative view of human host protein expression profiles regulated by bacterial infection. The availability of these proteomic data will provide new insights into biology and pathogenesis of these obligatory intracellular pathogens.« less

Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure

PubMed Central

Jorgensen, Elisa M.; Alderman, Myles H.; Taylor, Hugh S.

2016-01-01

Bisphenol-A (BPA) is an environmentally ubiquitous estrogen-like endocrine-disrupting compound. Exposure to BPA in utero has been linked to female reproductive disorders, including endometrial hyperplasia and breast cancer. Estrogens are an etiological factor in many of these conditions. We sought to determine whether in utero exposure to BPA altered the global CpG methylation pattern of the uterine genome, subsequent gene expression, and estrogen response. Pregnant mice were exposed to an environmentally relevant dose of BPA or DMSO control. Uterine DNA and RNA were examined by using methylated DNA immunoprecipitation methylation microarray, expression microarray, and quantitative PCR. In utero BPA exposure altered the global CpG methylation profile of the uterine genome and subsequent gene expression. The effect on gene expression was not apparent until sexual maturation, which suggested that estrogen response was the primary alteration. Indeed, prenatal BPA exposure preferentially altered adult estrogen-responsive gene expression. Changes in estrogen response were accompanied by altered methylation that preferentially affected estrogen receptor-α (ERα)–binding genes. The majority of genes that demonstrated both altered expression and ERα binding had decreased methylation. BPA selectively altered the normal developmental programming of estrogen-responsive genes via modification of the genes that bind ERα. Gene–environment interactions driven by early life xenoestrogen exposure likely contributes to increased risk of estrogen-related disease in adults.—Jorgensen, E. M., Alderman, M. H., III, Taylor, H. S. Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure. PMID:27312807

Predicting features of breast cancer with gene expression patterns.

PubMed

Lu, Xuesong; Lu, Xin; Wang, Zhigang C; Iglehart, J Dirk; Zhang, Xuegong; Richardson, Andrea L

2008-03-01

Data from gene expression arrays hold an enormous amount of biological information. We sought to determine if global gene expression in primary breast cancers contained information about biologic, histologic, and anatomic features of the disease in individual patients. Microarray data from the tumors of 129 patients were analyzed for the ability to predict biomarkers [estrogen receptor (ER) and HER2], histologic features [grade and lymphatic-vascular invasion (LVI)], and stage parameters (tumor size and lymph node metastasis). Multiple statistical predictors were used and the prediction accuracy was determined by cross-validation error rate; multidimensional scaling (MDS) allowed visualization of the predicted states under study. Models built from gene expression data accurately predict ER and HER2 status, and divide tumor grade into high-grade and low-grade clusters; intermediate-grade tumors are not a unique group. In contrast, gene expression data is inaccurate at predicting tumor size, lymph node status or LVI. The best model for prediction of nodal status included tumor size, LVI status and pathologically defined tumor subtype (based on combinations of ER, HER2, and grade); the addition of microarray-based prediction to this model failed to improve the prediction accuracy. Global gene expression supports a binary division of ER, HER2, and grade, clearly separating tumors into two categories; intermediate values for these bio-indicators do not define intermediate tumor subsets. Results are consistent with a model of regional metastasis that depends on inherent biologic differences in metastatic propensity between breast cancer subtypes, upon which time and chance then operate.

Gene expression patterns combined with network analysis identify hub genes associated with bladder cancer.

PubMed

Bi, Dongbin; Ning, Hao; Liu, Shuai; Que, Xinxiang; Ding, Kejia

2015-06-01

To explore molecular mechanisms of bladder cancer (BC), network strategy was used to find biomarkers for early detection and diagnosis. The differentially expressed genes (DEGs) between bladder carcinoma patients and normal subjects were screened using empirical Bayes method of the linear models for microarray data package. Co-expression networks were constructed by differentially co-expressed genes and links. Regulatory impact factors (RIF) metric was used to identify critical transcription factors (TFs). The protein-protein interaction (PPI) networks were constructed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and clusters were obtained through molecular complex detection (MCODE) algorithm. Centralities analyses for complex networks were performed based on degree, stress and betweenness. Enrichment analyses were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Co-expression networks and TFs (based on expression data of global DEGs and DEGs in different stages and grades) were identified. Hub genes of complex networks, such as UBE2C, ACTA2, FABP4, CKS2, FN1 and TOP2A, were also obtained according to analysis of degree. In gene enrichment analyses of global DEGs, cell adhesion, proteinaceous extracellular matrix and extracellular matrix structural constituent were top three GO terms. ECM-receptor interaction, focal adhesion, and cell cycle were significant pathways. Our results provide some potential underlying biomarkers of BC. However, further validation is required and deep studies are needed to elucidate the pathogenesis of BC. Copyright © 2015 Elsevier Ltd. All rights reserved.

Integrated Molecular Characterization of Testicular Germ Cell Tumors.

PubMed

Shen, Hui; Shih, Juliann; Hollern, Daniel P; Wang, Linghua; Bowlby, Reanne; Tickoo, Satish K; Thorsson, Vésteinn; Mungall, Andrew J; Newton, Yulia; Hegde, Apurva M; Armenia, Joshua; Sánchez-Vega, Francisco; Pluta, John; Pyle, Louise C; Mehra, Rohit; Reuter, Victor E; Godoy, Guilherme; Jones, Jeffrey; Shelley, Carl S; Feldman, Darren R; Vidal, Daniel O; Lessel, Davor; Kulis, Tomislav; Cárcano, Flavio M; Leraas, Kristen M; Lichtenberg, Tara M; Brooks, Denise; Cherniack, Andrew D; Cho, Juok; Heiman, David I; Kasaian, Katayoon; Liu, Minwei; Noble, Michael S; Xi, Liu; Zhang, Hailei; Zhou, Wanding; ZenKlusen, Jean C; Hutter, Carolyn M; Felau, Ina; Zhang, Jiashan; Schultz, Nikolaus; Getz, Gad; Meyerson, Matthew; Stuart, Joshua M; Akbani, Rehan; Wheeler, David A; Laird, Peter W; Nathanson, Katherine L; Cortessis, Victoria K; Hoadley, Katherine A

2018-06-12

We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance-KIT, KRAS, and NRAS-exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma. Striking differences in global DNA methylation and microRNA expression between histology subtypes highlight a likely role of epigenomic processes in determining histologic fates in TGCTs. We also identified a subset of pure seminomas defined by KIT mutations, increased immune infiltration, globally demethylated DNA, and decreased KRAS copy number. We report potential biomarkers for risk stratification, such as miRNA specifically expressed in teratoma, and others with molecular diagnostic potential, such as CpH (CpA/CpC/CpT) methylation identifying embryonal carcinomas. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

BRIC-17 Mapping Spaceflight-Induced Hypoxic Signaling and Response in Plants

NASA Technical Reports Server (NTRS)

Gilroy, Simon; Choi, Won-Gyu; Swanson, Sarah

2012-01-01

Goals of this work are: (1) Define global changes in gene expression patterns in Arabidopsis plants grown in microgravity using whole genome microarrays (2) Compare to mutants resistant to low oxygen challenge using whole genome microarrays Also measuring root and shoot size Outcomes from this research are: (1) Provide fundamental information on plant responses to the stresses inherent in spaceflight (2) Potential for informing on genetic strategies to engineer plants for optimal growth in space

The annual global economic burden of heart failure.

PubMed

Cook, Christopher; Cole, Graham; Asaria, Perviz; Jabbour, Richard; Francis, Darrel P

2014-02-15

Heart failure (HF) imposes both direct costs to healthcare systems and indirect costs to society through morbidity, unpaid care costs, premature mortality and lost productivity. The global economic burden of HF is not known. We estimated the overall cost of heart failure in 2012, in both direct and indirect terms, across the globe. Existing country-specific heart failure costs analyses were expressed as a proportion of gross domestic product and total healthcare spend. Using World Bank data, these proportional values were used to interpolate the economic cost of HF for countries of the world where no published data exists. Countries were categorized according to their level of economic development to investigate global patterns of spending. 197 countries were included in the analysis, covering 98.7% of the world's population. The overall economic cost of HF in 2012 was estimated at $108 billion per annum. Direct costs accounted for ~60% ($65 billion) and indirect costs accounted for ~40% ($43 billion) of the overall spend. Heart failure spending varied widely between high-income and middle and low-income countries. High-income countries spend a greater proportion on direct costs: a pattern reversed for middle and low-income countries. Heart failure imposes a huge economic burden, estimated at $108 billion per annum. With an aging, rapidly expanding and industrializing global population this value will continue to rise. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Short-term hyperglycaemia causes non-reversible changes in arterial gene expression in a fully 'switchable' in vivo mouse model of diabetes.

PubMed

Zervou, S; Wang, Y-F; Laiho, A; Gyenesei, A; Kytömäki, L; Hermann, R; Abouna, S; Epstein, D; Pelengaris, S; Khan, M

2010-12-01

Irreversible arterial damage due to early effects of hypo- or hyperglycaemia could account for the limited success of glucose-lowering treatments in preventing cardiovascular disease (CVD) events. We hypothesised that even brief hypo- or hyperglycaemia could adversely affect arterial gene expression and that these changes, moreover, might not be fully reversible. By controlled activation of a 'switchable' c-Myc transgene in beta cells, adult pIns-c-MycER(TAM) mice were rendered transiently hypo- and then hyperglycaemic, after which they were allowed to recover for up to 3 months. Immediate and sequential changes in aortic global gene expression from normal glycaemia through hypo- and hyperglycaemia to recovery were assessed. Gene expression was compared with that of normoglycaemic transgenic and tamoxifen-treated wild-type controls. Overall, expression of 95 genes was significantly affected by moderate hypoglycaemia (glucose down to 2.5 mmol/l), whereas over 769 genes were affected by hyperglycaemia. Genes and pathways activated included several involved in atherogenic processes, such as inflammation and arterial calcification. Although expression of many genes recovered to initial pre-exposure levels when hyperglycaemia was corrected (74.9%), in one in four genes this did not occur. Quantitative reverse transcriptase PCR and immunohistochemistry verified the gene expression patterns of key molecules, as shown by global gene arrays. Short-term exposure to hyperglycaemia can cause deleterious and persistent changes in arterial gene expression in vivo. Brief hypoglycaemia also adversely affects gene expression, although less substantially. Together, these results suggest that early correction of hyperglycaemia and avoidance of hypoglycaemia may both be necessary to avoid excess CVD risk in diabetes.

Maize Opaque Endosperm Mutations Create Extensive Changes in Patterns of Gene ExpressionW⃞

PubMed Central

Hunter, Brenda G.; Beatty, Mary K.; Singletary, George W.; Hamaker, Bruce R.; Dilkes, Brian P.; Larkins, Brian A.; Jung, Rudolf

2002-01-01

Maize starchy endosperm mutants have kernel phenotypes that include a brittle texture, susceptibility to insect pests, and inferior functional characteristics of products made from their flour. At least 18 such mutants have been identified, but only in the cases of opaque2 (o2) and floury2 (fl2), which affect different aspects of storage protein synthesis, is the molecular basis of the mutation known. To better understand the relationship between the phenotypes of these mutants and their biochemical bases, we characterized the protein and amino acid composition, as well as the mRNA transcript profiles, of nearly isogenic inbred lines of W64A o1, o2, o5, o9, o11, Mucuronate (Mc), Defective endosperm B30 (DeB30), and fl2. The largest reductions in zein protein synthesis occur in the W64A o2, DeB30, and fl2 mutants, which have ∼35 to 55% of the wild-type level of storage proteins. Zeins in W64A o5, o9, o11, and Mc are within 80 to 90% of the amount found in the wild type. Only in the cases of o5 and Mc were significant qualitative changes in zein synthesis observed. The pattern of gene expression in normal and mutant genotypes was assayed by profiling endosperm mRNA transcripts at 18 days after pollination with an Affymetrix GeneChip containing >1400 selected maize gene sequences. Compared with W64A sugary1, a mutant defective in starch synthesis, alterations in the gene expression patterns of the opaque mutants are very pleiotropic. Increased expression of genes associated with physiological stress, and the unfolded protein response, are common features of the opaque mutants. Based on global patterns of gene expression, these mutants were categorized in four phenotypic groups as follows: W64A+ and o1; o2; o5/o9/o11; and Mc and fl2. PMID:12368507

Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells

PubMed Central

Das, Rina; Hammamieh, Rasha; Neill, Roger; Ludwig, George V; Eker, Steven; Lincoln, Patrick; Ramamoorthy, Preveen; Dhokalia, Apsara; Mani, Sachin; Mendis, Chanaka; Cummings, Christiano; Kearney, Brian; Royaee, Atabak; Huang, Xiao-Zhe; Paranavitana, Chrysanthi; Smith, Leonard; Peel, Sheila; Kanesa-Thasan, Niranjan; Hoover, David; Lindler, Luther E; Yang, David; Henchal, Erik; Jett, Marti

2008-01-01

Background Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs. Methods To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays. Results We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin. Conclusion Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents. PMID:18667072

The Peripheral Olfactory Repertoire of the Lightbrown Apple Moth, Epiphyas postvittana

PubMed Central

Thrimawithana, Amali H.; Crowhurst, Ross N.; Newcomb, Richard D.

2015-01-01

The lightbrown apple moth, Epiphyas postvittana is an increasingly global pest of horticultural crops. Like other moths, E. postvittana relies on olfactory cues to locate mates and oviposition sites. To detect these cues, moths have evolved families of genes encoding elements of the peripheral olfactory reception system, including odor carriers, receptors and degrading enzymes. Here we undertake a transcriptomic approach to identify members of these families expressed in the adult antennae of E. postvittana, describing open reading frames encoding 34 odorant binding proteins, 13 chemosensory proteins, 70 odorant receptors, 19 ionotropic receptors, nine gustatory receptors, two sensory neuron membrane proteins, 27 carboxylesterases, 20 glutathione-S-transferases, 49 cytochrome p450s and 18 takeout proteins. For the odorant receptors, quantitative RT-PCR corroborated RNAseq count data on steady state transcript levels. Of the eight odorant receptors that group phylogenetically with pheromone receptors from other moths, two displayed significant male-biased expression patterns, one displayed significant female-biased expression pattern and five were expressed equally in the antennae of both sexes. In addition, we found two male-biased odorant receptors that did not group with previously described pheromone receptors. This suite of olfaction-related genes provides a substantial resource for the functional characterization of this signal transduction system and the development of odor-mediated control strategies for horticultural pests. PMID:26017144

Whole Genome Gene Expression Meta-Analysis of Inflammatory Bowel Disease Colon Mucosa Demonstrates Lack of Major Differences between Crohn's Disease and Ulcerative Colitis

PubMed Central

Østvik, Ann E.; Drozdov, Ignat; Gustafsson, Bjørn I.; Kidd, Mark; Beisvag, Vidar; Torp, Sverre H.; Waldum, Helge L.; Martinsen, Tom Christian; Damås, Jan Kristian; Espevik, Terje; Sandvik, Arne K.

2013-01-01

Background In inflammatory bowel disease (IBD), genetic susceptibility together with environmental factors disturbs gut homeostasis producing chronic inflammation. The two main IBD subtypes are Ulcerative colitis (UC) and Crohn’s disease (CD). We present the to-date largest microarray gene expression study on IBD encompassing both inflamed and un-inflamed colonic tissue. A meta-analysis including all available, comparable data was used to explore important aspects of IBD inflammation, thereby validating consistent gene expression patterns. Methods Colon pinch biopsies from IBD patients were analysed using Illumina whole genome gene expression technology. Differential expression (DE) was identified using LIMMA linear model in the R statistical computing environment. Results were enriched for gene ontology (GO) categories. Sets of genes encoding antimicrobial proteins (AMP) and proteins involved in T helper (Th) cell differentiation were used in the interpretation of the results. All available data sets were analysed using the same methods, and results were compared on a global and focused level as t-scores. Results Gene expression in inflamed mucosa from UC and CD are remarkably similar. The meta-analysis confirmed this. The patterns of AMP and Th cell-related gene expression were also very similar, except for IL23A which was consistently higher expressed in UC than in CD. Un-inflamed tissue from patients demonstrated minimal differences from healthy controls. Conclusions There is no difference in the Th subgroup involvement between UC and CD. Th1/Th17 related expression, with little Th2 differentiation, dominated both diseases. The different IL23A expression between UC and CD suggests an IBD subtype specific role. AMPs, previously little studied, are strongly overexpressed in IBD. The presented meta-analysis provides a sound background for further research on IBD pathobiology. PMID:23468882

Whole genome gene expression meta-analysis of inflammatory bowel disease colon mucosa demonstrates lack of major differences between Crohn's disease and ulcerative colitis.

PubMed

Granlund, Atle van Beelen; Flatberg, Arnar; Østvik, Ann E; Drozdov, Ignat; Gustafsson, Bjørn I; Kidd, Mark; Beisvag, Vidar; Torp, Sverre H; Waldum, Helge L; Martinsen, Tom Christian; Damås, Jan Kristian; Espevik, Terje; Sandvik, Arne K

2013-01-01

In inflammatory bowel disease (IBD), genetic susceptibility together with environmental factors disturbs gut homeostasis producing chronic inflammation. The two main IBD subtypes are Ulcerative colitis (UC) and Crohn's disease (CD). We present the to-date largest microarray gene expression study on IBD encompassing both inflamed and un-inflamed colonic tissue. A meta-analysis including all available, comparable data was used to explore important aspects of IBD inflammation, thereby validating consistent gene expression patterns. Colon pinch biopsies from IBD patients were analysed using Illumina whole genome gene expression technology. Differential expression (DE) was identified using LIMMA linear model in the R statistical computing environment. Results were enriched for gene ontology (GO) categories. Sets of genes encoding antimicrobial proteins (AMP) and proteins involved in T helper (Th) cell differentiation were used in the interpretation of the results. All available data sets were analysed using the same methods, and results were compared on a global and focused level as t-scores. Gene expression in inflamed mucosa from UC and CD are remarkably similar. The meta-analysis confirmed this. The patterns of AMP and Th cell-related gene expression were also very similar, except for IL23A which was consistently higher expressed in UC than in CD. Un-inflamed tissue from patients demonstrated minimal differences from healthy controls. There is no difference in the Th subgroup involvement between UC and CD. Th1/Th17 related expression, with little Th2 differentiation, dominated both diseases. The different IL23A expression between UC and CD suggests an IBD subtype specific role. AMPs, previously little studied, are strongly overexpressed in IBD. The presented meta-analysis provides a sound background for further research on IBD pathobiology.

Characterization of the transcriptome profiles related to globin gene switching during in vitro erythroid maturation

PubMed Central

2012-01-01

Background The fetal and adult globin genes in the human β-globin cluster on chromosome 11 are sequentially expressed to achieve normal hemoglobin switching during human development. The pharmacological induction of fetal γ-globin (HBG) to replace abnormal adult sickle βS-globin is a successful strategy to treat sickle cell disease; however the molecular mechanism of γ-gene silencing after birth is not fully understood. Therefore, we performed global gene expression profiling using primary erythroid progenitors grown from human peripheral blood mononuclear cells to characterize gene expression patterns during the γ-globin to β-globin (γ/β) switch observed throughout in vitro erythroid differentiation. Results We confirmed erythroid maturation in our culture system using cell morphologic features defined by Giemsa staining and the γ/β-globin switch by reverse transcription-quantitative PCR (RT-qPCR) analysis. We observed maximal γ-globin expression at day 7 with a switch to a predominance of β-globin expression by day 28 and the γ/β-globin switch occurred around day 21. Expression patterns for transcription factors including GATA1, GATA2, KLF1 and NFE2 confirmed our system produced the expected pattern of expression based on the known function of these factors in globin gene regulation. Subsequent gene expression profiling was performed with RNA isolated from progenitors harvested at day 7, 14, 21, and 28 in culture. Three major gene profiles were generated by Principal Component Analysis (PCA). For profile-1 genes, where expression decreased from day 7 to day 28, we identified 2,102 genes down-regulated > 1.5-fold. Ingenuity pathway analysis (IPA) for profile-1 genes demonstrated involvement of the Cdc42, phospholipase C, NF-Kβ, Interleukin-4, and p38 mitogen activated protein kinase (MAPK) signaling pathways. Transcription factors known to be involved in γ-and β-globin regulation were identified. The same approach was used to generate profile-2 genes where expression was up-regulated over 28 days in culture. IPA for the 2,437 genes with > 1.5-fold induction identified the mitotic roles of polo-like kinase, aryl hydrocarbon receptor, cell cycle control, and ATM (Ataxia Telangiectasia Mutated Protein) signaling pathways; transcription factors identified included KLF1, GATA1 and NFE2 among others. Finally, profile-3 was generated from 1,579 genes with maximal expression at day 21, around the time of the γ/β-globin switch. IPA identified associations with cell cycle control, ATM, and aryl hydrocarbon receptor signaling pathways. Conclusions The transcriptome analysis completed with erythroid progenitors grown in vitro identified groups of genes with distinct expression profiles, which function in metabolic pathways associated with cell survival, hematopoiesis, blood cells activation, and inflammatory responses. This study represents the first report of a transcriptome analysis in human primary erythroid progenitors to identify transcription factors involved in hemoglobin switching. Our results also demonstrate that the in vitro liquid culture system is an excellent model to define mechanisms of global gene expression and the DNA-binding protein and signaling pathways involved in globin gene regulation. PMID:22537182

Genome-wide Hi-C analysis reveals extensive hierarchical chromatin interactions in rice.

PubMed

Dong, Qianli; Li, Ning; Li, Xiaochong; Yuan, Zan; Xie, Dejian; Wang, Xiaofei; Li, Jianing; Yu, Yanan; Wang, Jinbin; Ding, Baoxu; Zhang, Zhibin; Li, Changping; Bian, Yao; Zhang, Ai; Wu, Ying; Liu, Bao; Gong, Lei

2018-06-01

The non-random spatial packing of chromosomes in the nucleus plays a critical role in orchestrating gene expression and genome function. Here, we present a Hi-C analysis of the chromatin interaction patterns in rice (Oryza sativa L.) at hierarchical architectural levels. We confirm that rice chromosomes occupy their own territories with certain preferential inter-chromosomal associations. Moderate compartment delimitation and extensive TADs (Topologically Associated Domains) were determined to be associated with heterogeneous genomic compositions and epigenetic marks in the rice genome. We found subtle features including chromatin loops, gene loops, and off-/near-diagonal intensive interaction regions. Gene chromatin loops associated with H3K27me3 could be positively involved in gene expression. In addition to insulated enhancing effects for neighbor gene expression, the identified rice gene loops could bi-directionally (+/-) affect the expression of looped genes themselves. Finally, web-interleaved off-diagonal IHIs/KEEs (Interactive Heterochromatic Islands or KNOT ENGAGED ELEMENTs) could trap transposable elements (TEs) via the enrichment of silencing epigenetic marks. In parallel, the near-diagonal FIREs (Frequently Interacting Regions) could positively affect the expression of involved genes. Our results suggest that the chromatin packing pattern in rice is generally similar to that in Arabidopsis thaliana but with clear differences at specific structural levels. We conclude that genomic composition, epigenetic modification, and transcriptional activity could act in combination to shape global and local chromatin packing in rice. Our results confirm recent observations in rice and A. thaliana but also provide additional insights into the patterns and features of chromatin organization in higher plants. © 2018 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

Diurnal Cycling Transcription Factors of Pineapple Revealed by Genome-Wide Annotation and Global Transcriptomic Analysis.

PubMed

Sharma, Anupma; Wai, Ching Man; Ming, Ray; Yu, Qingyi

2017-09-01

Circadian clock provides fitness advantage by coordinating internal metabolic and physiological processes to external cyclic environments. Core clock components exhibit daily rhythmic changes in gene expression, and the majority of them are transcription factors (TFs) and transcription coregulators (TCs). We annotated 1,398 TFs from 67 TF families and 80 TCs from 20 TC families in pineapple, and analyzed their tissue-specific and diurnal expression patterns. Approximately 42% of TFs and 45% of TCs displayed diel rhythmic expression, including 177 TF/TCs cycling only in the nonphotosynthetic leaf tissue, 247 cycling only in the photosynthetic leaf tissue, and 201 cycling in both. We identified 68 TF/TCs whose cycling expression was tightly coupled between the photosynthetic and nonphotosynthetic leaf tissues. These TF/TCs likely coordinate key biological processes in pineapple as we demonstrated that this group is enriched in homologous genes that form the core circadian clock in Arabidopsis and includes a STOP1 homolog. Two lines of evidence support the important role of the STOP1 homolog in regulating CAM photosynthesis in pineapple. First, STOP1 responds to acidic pH and regulates a malate channel in multiple plant species. Second, the cycling expression pattern of the pineapple STOP1 and the diurnal pattern of malate accumulation in pineapple leaf are correlated. We further examined duplicate-gene retention and loss in major known circadian genes and refined their evolutionary relationships between pineapple and other plants. Significant variations in duplicate-gene retention and loss were observed for most clock genes in both monocots and dicots. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Three-pattern decomposition of global atmospheric circulation: part II—dynamical equations of horizontal, meridional and zonal circulations

NASA Astrophysics Data System (ADS)

Hu, Shujuan; Cheng, Jianbo; Xu, Ming; Chou, Jifan

2018-04-01

The three-pattern decomposition of global atmospheric circulation (TPDGAC) partitions three-dimensional (3D) atmospheric circulation into horizontal, meridional and zonal components to study the 3D structures of global atmospheric circulation. This paper incorporates the three-pattern decomposition model (TPDM) into primitive equations of atmospheric dynamics and establishes a new set of dynamical equations of the horizontal, meridional and zonal circulations in which the operator properties are studied and energy conservation laws are preserved, as in the primitive equations. The physical significance of the newly established equations is demonstrated. Our findings reveal that the new equations are essentially the 3D vorticity equations of atmosphere and that the time evolution rules of the horizontal, meridional and zonal circulations can be described from the perspective of 3D vorticity evolution. The new set of dynamical equations includes decomposed expressions that can be used to explore the source terms of large-scale atmospheric circulation variations. A simplified model is presented to demonstrate the potential applications of the new equations for studying the dynamics of the Rossby, Hadley and Walker circulations. The model shows that the horizontal air temperature anomaly gradient (ATAG) induces changes in meridional and zonal circulations and promotes the baroclinic evolution of the horizontal circulation. The simplified model also indicates that the absolute vorticity of the horizontal circulation is not conserved, and its changes can be described by changes in the vertical vorticities of the meridional and zonal circulations. Moreover, the thermodynamic equation shows that the induced meridional and zonal circulations and advection transport by the horizontal circulation in turn cause a redistribution of the air temperature. The simplified model reveals the fundamental rules between the evolution of the air temperature and the horizontal, meridional and zonal components of global atmospheric circulation.

Is "Warm Arctic, Cold Continent" A Fingerprint Pattern of Climate Change?

NASA Astrophysics Data System (ADS)

Hoerling, M. P.; Sun, L.; Perlwitz, J.

2015-12-01

Cold winters and cold waves have recently occurred in Europe, central Asia and the Midwest to eastern United States, even as global mean temperatures set record highs and Arctic amplification of surface warming continued. Since 1979, Central Asia winter temperatures have in fact declined. Conjecture has it that more cold extremes over the mid-latitude continents should occur due to global warming and the impacts of Arctic sea ice loss. A Northern Hemisphere temperature signal termed the "Warm Arctic, Cold Continent" pattern has thus been surmised. Here we use a multi-model approach to test the hypothesis that such a pattern is indeed symptomatic of climate change. Diagnosis of a large model ensemble of historical climate simulations shows some individual realizations to yield cooling trends over Central Asia, but importantly the vast majority show warming. The observed cooling has thus likely been a low probability state of internal variability, not a fingerprint of forced climate change. We show that daily temperature variations over continents decline in winter due to global warming, and cold waves become less likely. This is partly related to diminution of Arctic cold air reservoirs due to warming-induced sea ice loss. Nonetheless, we find some evidence and present a physical basis that Arctic sea ice loss alone can induce a winter cooling over Central Asia, though with a magnitude that is appreciably smaller than the overall radiative-forced warming signal. Our results support the argument that recent cooling trends over central Asia, and cold extreme events over the winter continents, have principally resulted from atmospheric internal variability and have been neither a forced response to Arctic seas ice loss nor a symptom of global warming. The paradigm of climate change is thus better expressed as "Warm Arctic, Warm Continent" for the NH winter.

The nature of electron acceptor (MnIV/NO3) triggers differential expression of genes associated with stress and ammonium limitation responses in Shewanella algae C6G3.

PubMed

Aigle, Axel; Bonin, Patricia; -Nunez, Nicolas Fernandez; Loriod, Béatrice; Guasco, Sophie; Bergon, Aurélie; Armougom, Fabrice; Iobbi-Nivol, Chantal; Imbert, Jean; Michotey, Valérie

2018-03-16

Shewanella algae C6G3 can reduce dissimilatively nitrate into ammonium and manganese-oxide (MnIV) into MnII. It has the unusual ability to produce anaerobically nitrite from ammonium in the presence of MnIV. To gain insight into their metabolic capabilities, global mRNA expression patterns were investigated by RNA-seq and qRT-PCR in cells growing with lactate and ammonium as carbon and nitrogen sources and with either MnIV or nitrate as electron acceptors. Gene exhibiting higher expression levels in the presence of MnIV belonged to functional categories of carbohydrate, coenzyme, lipid metabolisms and inorganic ion transport. Comparative transcriptomic pattern between MnIV and NO3 revealed that the strain presented an ammonium limitation status with MnIV, despite the presence of non-limiting concentration of ammonium under both culture conditions. In addition, in presence of MnIV, ntrB/nrtC regulators, ammonium channel, nitrogen regulatory protein P-II, glutamine synthetase and asparagine synthetase glutamine dependent genes were over-represented. Under nitrate condition, the expression of genes involved in the synthesis of several amino acids was increased. Finally, expression level of genes associated with the general stress response was also amplified and among them, katE, a putative catalase/peroxidase present on several Shewanella genomes, was highly expressed with a relative median value higher in MnIV condition.

Auxins upregulate nif and fix genes.

PubMed

Bianco, Carmen; Defez, Roberto

2010-10-01

In a recent publication we analyzed the global effects triggered by IAA overproduction in S. meliloti RD64 under free-living conditions by comparing the gene expression pattern of wild type 1021 with that of RD64 and 1021 treated with IAA and other four chemically or functionally related molecules. Among the genes differentially expressed in RD64 and IAA-treated 1021 cells we found two genes of pho operon, phoT and phoC. Based on this finding we examined the mechanisms for mineral P solubilization in RD64 and the potential ability of this strain to improve Medicago growth under P-starved conditions. Here, we further analyze the expression profiles obtained in microarray analysis and evaluate the specificity and the extent of overlap between all treatments. Venn diagrams indicated that IAA- and 2,4-D-regulated genes were closely related. Furthermore, most differentially expressed genes from pSymA were induced in 1021 cells treated with 2,4-D, ICA, IND and Trp as compared to the untreated 1021 cells. RT-PCR analysis was employed to analyze the differential expression patterns of nitrogen fixation genes under free-living and symbiotic conditions. Under symbiotic condition, the relative expression levels of nif and fix genes were significantly induced in Mt- RD64 plants and in Mt-1021 plants treated with IAA and 2,4-D whereas they were unchanged or repressed in Mt-1021 plants treated with the other selected compounds when compared to the untreated Mt-1021 plants. © 2010 Landes Bioscience

Coordinated dysregulation of mRNAs and microRNAs in the rat medial prefrontal cortex following a history of alcohol dependence

PubMed Central

Tapocik, Jenica D.; Solomon, Matthew; Flanigan, Meghan; Meinhardt, Marcus; Barbier, Estelle; Schank, Jesse; Schwandt, Melanie; Sommer, Wolfgang H.; Heilig, Markus

2012-01-01

Long-term changes in brain gene expression have been identified in alcohol dependence, but underlying mechanisms remain unknown. Here, we examined the potential role of microRNAs for persistent gene expression changes in the rat medial prefrontal cortex after a history of alcohol dependence. Two-bottle free-choice alcohol consumption increased following 7-week exposure to intermittent alcohol intoxication. A bioinformatic approach using microarray analysis, qPCR, bioinformatic analysis, and microRNA-mRNA integrative analysis identified expression patterns indicative of a disruption in synaptic processes and neuroplasticity. 41 rat-microRNAs and 165 mRNAs in the medial prefrontal cortex were significantly altered after chronic alcohol exposure. A subset of the microRNAs and mRNAs was confirmed by qPCR. Gene ontology categories of differential expression pointed to functional processes commonly associated with neurotransmission, neuroadaptation, and synaptic plasticity. microRNA-mRNA expression pairing identified 33 microRNAs putatively targeting 89 mRNAs suggesting transcriptional networks involved in axonal guidance and neurotransmitter signaling. Our results demonstrate a significant shift in microRNA expression patterns in the medial prefrontal cortex following a history of dependence. Due to their global regulation of multiple downstream target transcripts, microRNAs may play a pivotal role in the reorganization of synaptic connections and long term neuroadaptations in alcohol dependence. microRNA-mediated alterations of transcriptional networks may be involved in disrupted prefrontal control over alcohol-drinking observed in alcoholic patients. PMID:22614244

Site-specific variation in gene expression from Symbiodinium spp. associated with offshore and inshore Porites astreoides in the lower Florida Keys is lost with bleaching and disease stress.

PubMed

Salas, Briana Hauff; Haslun, Joshua A; Strychar, Kevin B; Ostrom, Peggy H; Cervino, James M

2017-01-01

Scleractinian coral are experiencing unprecedented rates of mortality due to increases in sea surface temperatures in response to global climate change. Some coral species however, survive high temperature events due to a reduced susceptibility to bleaching. We investigated the relationship between bleaching susceptibility and expression of five metabolically related genes of Symbiodinium spp. from the coral Porites astreoides originating from an inshore and offshore reef in the Florida Keys. The acclimatization potential of Symbiodinium spp. to changing temperature regimes was also measured via a two-year reciprocal transplant between the sites. Offshore coral fragments displayed significantly higher expression in Symbiodinium spp. genes PCNA, SCP2, G3PDH, PCP and psaE than their inshore counterparts (p<0.05), a pattern consistent with increased bleaching susceptibility in offshore corals. Additionally, gene expression patterns in Symbiodinium spp. from site of origin were conserved throughout the two-year reciprocal transplant, indicating acclimatization did not occur within this multi-season time frame. Further, laboratory experiments were used to investigate the influence of acute high temperature (32°C for eight hours) and disease (lipopolysaccharide of Serratia marcescens) on the five metabolically related symbiont genes from the same offshore and inshore P. astreoides fragments. Gene expression did not differ between reef fragments, or as a consequence of acute exposure to heat or heat and disease, contrasting to results found in the field. Gene expression reported here indicates functional variation in populations of Symbiodinium spp. associated with P. astreoides in the Florida Keys, and is likely a result of localized adaptation. However, gene expression patterns observed in the lab imply that functional variation in zooxanthellae observed under conditions of chronic moderate stress is lost under the acute extreme conditions studied here.

Site-specific variation in gene expression from Symbiodinium spp. associated with offshore and inshore Porites astreoides in the lower Florida Keys is lost with bleaching and disease stress

PubMed Central

Haslun, Joshua A.; Strychar, Kevin B.; Ostrom, Peggy H.; Cervino, James M.

2017-01-01

Scleractinian coral are experiencing unprecedented rates of mortality due to increases in sea surface temperatures in response to global climate change. Some coral species however, survive high temperature events due to a reduced susceptibility to bleaching. We investigated the relationship between bleaching susceptibility and expression of five metabolically related genes of Symbiodinium spp. from the coral Porites astreoides originating from an inshore and offshore reef in the Florida Keys. The acclimatization potential of Symbiodinium spp. to changing temperature regimes was also measured via a two-year reciprocal transplant between the sites. Offshore coral fragments displayed significantly higher expression in Symbiodinium spp. genes PCNA, SCP2, G3PDH, PCP and psaE than their inshore counterparts (p<0.05), a pattern consistent with increased bleaching susceptibility in offshore corals. Additionally, gene expression patterns in Symbiodinium spp. from site of origin were conserved throughout the two-year reciprocal transplant, indicating acclimatization did not occur within this multi-season time frame. Further, laboratory experiments were used to investigate the influence of acute high temperature (32°C for eight hours) and disease (lipopolysaccharide of Serratia marcescens) on the five metabolically related symbiont genes from the same offshore and inshore P. astreoides fragments. Gene expression did not differ between reef fragments, or as a consequence of acute exposure to heat or heat and disease, contrasting to results found in the field. Gene expression reported here indicates functional variation in populations of Symbiodinium spp. associated with P. astreoides in the Florida Keys, and is likely a result of localized adaptation. However, gene expression patterns observed in the lab imply that functional variation in zooxanthellae observed under conditions of chronic moderate stress is lost under the acute extreme conditions studied here. PMID:28355291

Identification of human cell responses to benzene and benzene metabolites.

PubMed

Gillis, Bruce; Gavin, Igor M; Arbieva, Zarema; King, Stephen T; Jayaraman, Sundararajan; Prabhakar, Bellur S

2007-09-01

Benzene is a common air pollutant and confirmed carcinogen, especially in reference to the hematopoietic system. In the present study we analyzed cytokine/chemokine production by, and gene expression induction in, human peripheral blood mononuclear cells upon their exposure to the benzene metabolites catechol, hydroquinone, 1,2,4-benzenetriol, and p-benzoquinone. Protein profiling showed that benzene metabolites can stimulate the production of chemokines, the proinflammatory cytokines TNF-alpha and IL-6, and the Th2 cytokines IL-4 and IL-5. Activated cells showed concurrent suppression of anti-inflammatory cytokine IL-10 expression. We also identified changes in global gene expression patterns in response to benzene metabolite challenges by using high-density oligonucleotide microarrays. Treatment with 1,2,4-benzenetriol resulted in the suppression of genes related to the regulation of protein expression and a concomitant activation of genes that encode heat shock proteins and cytochrome P450 family members. Protein and gene expression profiling identified unique human cellular responses upon exposure to benzene and benzene metabolites.

Intuitive Face Judgments Rely on Holistic Eye Movement Pattern

PubMed Central

Mega, Laura F.; Volz, Kirsten G.

2017-01-01

Non-verbal signals such as facial expressions are of paramount importance for social encounters. Their perception predominantly occurs without conscious awareness and is effortlessly integrated into social interactions. In other words, face perception is intuitive. Contrary to classical intuition tasks, this work investigates intuitive processes in the realm of every-day type social judgments. Two differently instructed groups of participants judged the authenticity of emotional facial expressions, while their eye movements were recorded: an ‘intuitive group,’ instructed to rely on their “gut feeling” for the authenticity judgments, and a ‘deliberative group,’ instructed to make their judgments after careful analysis of the face. Pixel-wise statistical maps of the resulting eye movements revealed a differential viewing pattern, wherein the intuitive judgments relied on fewer, longer and more centrally located fixations. These markers have been associated with a global/holistic viewing strategy. The holistic pattern of intuitive face judgments is in line with evidence showing that intuition is related to processing the “gestalt” of an object, rather than focusing on details. Our work thereby provides further evidence that intuitive processes are characterized by holistic perception, in an understudied and real world domain of intuition research. PMID:28676773

Intuitive Face Judgments Rely on Holistic Eye Movement Pattern.

PubMed

Mega, Laura F; Volz, Kirsten G

2017-01-01

Non-verbal signals such as facial expressions are of paramount importance for social encounters. Their perception predominantly occurs without conscious awareness and is effortlessly integrated into social interactions. In other words, face perception is intuitive. Contrary to classical intuition tasks, this work investigates intuitive processes in the realm of every-day type social judgments. Two differently instructed groups of participants judged the authenticity of emotional facial expressions, while their eye movements were recorded: an 'intuitive group,' instructed to rely on their "gut feeling" for the authenticity judgments, and a 'deliberative group,' instructed to make their judgments after careful analysis of the face. Pixel-wise statistical maps of the resulting eye movements revealed a differential viewing pattern, wherein the intuitive judgments relied on fewer, longer and more centrally located fixations. These markers have been associated with a global/holistic viewing strategy. The holistic pattern of intuitive face judgments is in line with evidence showing that intuition is related to processing the "gestalt" of an object, rather than focusing on details. Our work thereby provides further evidence that intuitive processes are characterized by holistic perception, in an understudied and real world domain of intuition research.

Dimorphic DNA methylation during temperature-dependent sex determination in the sea turtle Lepidochelys olivacea.

PubMed

Venegas, Daniela; Marmolejo-Valencia, Alejandro; Valdes-Quezada, Christian; Govenzensky, Tzipe; Recillas-Targa, Félix; Merchant-Larios, Horacio

2016-09-15

Sex determination in vertebrates depends on the expression of a conserved network of genes. Sea turtles such as Lepidochelys olivacea have temperature-dependent sex determination. The present work analyses some of the epigenetic processes involved in this. We describe sexual dimorphism in global DNA methylation patterns between ovaries and testes of L. olivacea and show that the differences may arise from a combination of DNA methylation and demethylation events that occur during sex determination. Irrespective of incubation temperature, 5-hydroxymethylcytosine was abundant in the bipotential gonad; however, following sex determination, this modification was no longer found in pre-Sertoli cells in the testes. These changes correlate with the establishment of the sexually dimorphic DNA methylation patterns, down regulation of Sox9 gene expression in ovaries and irreversible gonadal commitment towards a male or female differentiation pathway. Thus, DNA methylation changes may be necessary for the stabilization of the gene expression networks that drive the differentiation of the bipotential gonad to form either an ovary or a testis in L. olivacea and probably among other species that manifest temperature-dependent sex determination. Copyright © 2016 Elsevier Inc. All rights reserved.

Protein-DNA binding dynamics predict transcriptional response to nutrients in archaea.

PubMed

Todor, Horia; Sharma, Kriti; Pittman, Adrianne M C; Schmid, Amy K

2013-10-01

Organisms across all three domains of life use gene regulatory networks (GRNs) to integrate varied stimuli into coherent transcriptional responses to environmental pressures. However, inferring GRN topology and regulatory causality remains a central challenge in systems biology. Previous work characterized TrmB as a global metabolic transcription factor in archaeal extremophiles. However, it remains unclear how TrmB dynamically regulates its ∼100 metabolic enzyme-coding gene targets. Using a dynamic perturbation approach, we elucidate the topology of the TrmB metabolic GRN in the model archaeon Halobacterium salinarum. Clustering of dynamic gene expression patterns reveals that TrmB functions alone to regulate central metabolic enzyme-coding genes but cooperates with various regulators to control peripheral metabolic pathways. Using a dynamical model, we predict gene expression patterns for some TrmB-dependent promoters and infer secondary regulators for others. Our data suggest feed-forward gene regulatory topology for cobalamin biosynthesis. In contrast, purine biosynthesis appears to require TrmB-independent regulators. We conclude that TrmB is an important component for mediating metabolic modularity, integrating nutrient status and regulating gene expression dynamics alone and in concert with secondary regulators.

DNA methylation by DNMT1 and DNMT3b methyltransferases is driven by the MUC1-C oncoprotein in human carcinoma cells.

PubMed

Rajabi, H; Tagde, A; Alam, M; Bouillez, A; Pitroda, S; Suzuki, Y; Kufe, D

2016-12-15

Aberrant expression of the DNA methyltransferases (DNMTs) and disruption of DNA methylation patterns are associated with carcinogenesis and cancer cell survival. The oncogenic MUC1-C protein is aberrantly overexpressed in diverse carcinomas; however, there is no known link between MUC1-C and DNA methylation. Our results demonstrate that MUC1-C induces the expression of DNMT1 and DNMT3b, but not DNMT3a, in breast and other carcinoma cell types. We show that MUC1-C occupies the DNMT1 and DNMT3b promoters in complexes with NF-κB p65 and drives DNMT1 and DNMT3b transcription. In this way, MUC1-C controls global DNA methylation as determined by analysis of LINE-1 repeat elements. The results further demonstrate that targeting MUC1-C downregulates DNA methylation of the CDH1 tumor suppressor gene in association with induction of E-cadherin expression. These findings provide compelling evidence that MUC1-C is of functional importance to induction of DNMT1 and DNMT3b and, in turn, changes in DNA methylation patterns in cancer cells.

MYCN controls an alternative RNA splicing program in high-risk metastatic neuroblastoma.

PubMed

Zhang, Shile; Wei, Jun S; Li, Samuel Q; Badgett, Tom C; Song, Young K; Agarwal, Saurabh; Coarfa, Cristian; Tolman, Catherine; Hurd, Laura; Liao, Hongling; He, Jianbin; Wen, Xinyu; Liu, Zhihui; Thiele, Carol J; Westermann, Frank; Asgharzadeh, Shahab; Seeger, Robert C; Maris, John M; Guidry Auvil, Jamie M; Smith, Malcolm A; Kolaczyk, Eric D; Shohet, Jason; Khan, Javed

2016-02-28

The molecular mechanisms underlying the aggressive behavior of MYCN driven neuroblastoma (NBL) is under intense investigation; however, little is known about the impact of this family of transcription factors on the splicing program. Here we used high-throughput RNA sequencing to systematically study the expression of RNA isoforms in stage 4 MYCN-amplified NBL, an aggressive subtype of metastatic NBL. We show that MYCN-amplified NBL tumors display a distinct gene splicing pattern affecting multiple cancer hallmark functions. Six splicing factors displayed unique differential expression patterns in MYCN-amplified tumors and cell lines, and the binding motifs for some of these splicing factors are significantly enriched in differentially-spliced genes. Direct binding of MYCN to promoter regions of the splicing factors PTBP1 and HNRNPA1 detected by ChIP-seq demonstrates that MYCN controls the splicing pattern by direct regulation of the expression of these key splicing factors. Furthermore, high expression of PTBP1 and HNRNPA1 was significantly associated with poor overall survival of stage4 NBL patients (p ≤ 0.05). Knocking down PTBP1, HNRNPA1 and their downstream target PKM2, an isoform of pro-tumor-growth, result in repressed growth of NBL cells. Therefore, our study reveals a novel role of MYCN in controlling global splicing program through regulation of splicing factors in addition to its well-known role in the transcription program. These findings suggest a therapeutically potential to target the key splicing factors or gene isoforms in high-risk NBL with MYCN-amplification. Published by Elsevier Ireland Ltd.

Gene expression patterns and dynamics of the colonization of common bean (Phaseolus vulgaris L.) by highly virulent and weakly virulent strains of Fusarium oxysporum

PubMed Central

Niño-Sánchez, Jonathan; Tello, Vega; Casado-del Castillo, Virginia; Thon, Michael R.; Benito, Ernesto P.; Díaz-Mínguez, José María

2015-01-01

The dynamics of root and hypocotyl colonization, and the gene expression patterns of several fungal virulence factors and plant defense factors have been analyzed and compared in the interaction of two Fusarium oxysporum f. sp. phaseoli strains displaying clear differences in virulence, with a susceptible common bean cultivar. The growth of the two strains on the root surface and the colonization of the root was quantitatively similar although the highly virulent (HV) strain was more efficient reaching the central root cylinder. The main differences between both strains were found in the temporal and spatial dynamics of crown root and hypocotyl colonization. The increase of fungal biomass in the crown root was considerably larger for the HV strain, which, after an initial stage of global colonization of both the vascular cylinder and the parenchymal cells, restricted its growth to the newly differentiated xylem vessels. The weakly virulent (WV) strain was a much slower and less efficient colonizer of the xylem vessels, showing also growth in the intercellular spaces of the parenchyma. Most of the virulence genes analyzed showed similar expression patterns in both strains, except SIX1, SIX6 and the gene encoding the transcription factor FTF1, which were highly upregulated in root crown and hypocotyl. The response induced in the infected plant showed interesting differences for both strains. The WV strain induced an early and strong transcription of the PR1 gene, involved in SAR response, while the HV strain preferentially induced the early expression of the ethylene responsive factor ERF2. PMID:25883592

Global Landscape of a Co-Expressed Gene Network in Barley and its Application to Gene Discovery in Triticeae Crops

PubMed Central

Mochida, Keiichi; Uehara-Yamaguchi, Yukiko; Yoshida, Takuhiro; Sakurai, Tetsuya; Shinozaki, Kazuo

2011-01-01

Accumulated transcriptome data can be used to investigate regulatory networks of genes involved in various biological systems. Co-expression analysis data sets generated from comprehensively collected transcriptome data sets now represent efficient resources that are capable of facilitating the discovery of genes with closely correlated expression patterns. In order to construct a co-expression network for barley, we analyzed 45 publicly available experimental series, which are composed of 1,347 sets of GeneChip data for barley. On the basis of a gene-to-gene weighted correlation coefficient, we constructed a global barley co-expression network and classified it into clusters of subnetwork modules. The resulting clusters are candidates for functional regulatory modules in the barley transcriptome. To annotate each of the modules, we performed comparative annotation using genes in Arabidopsis and Brachypodium distachyon. On the basis of a comparative analysis between barley and two model species, we investigated functional properties from the representative distributions of the gene ontology (GO) terms. Modules putatively involved in drought stress response and cellulose biogenesis have been identified. These modules are discussed to demonstrate the effectiveness of the co-expression analysis. Furthermore, we applied the data set of co-expressed genes coupled with comparative analysis in attempts to discover potentially Triticeae-specific network modules. These results demonstrate that analysis of the co-expression network of the barley transcriptome together with comparative analysis should promote the process of gene discovery in barley. Furthermore, the insights obtained should be transferable to investigations of Triticeae plants. The associated data set generated in this analysis is publicly accessible at http://coexpression.psc.riken.jp/barley/. PMID:21441235

Analysis of Gene Expression and Physiological Responses in Three Mexican Maize Landraces under Drought Stress and Recovery Irrigation

PubMed Central

Hayano-Kanashiro, Corina; Calderón-Vázquez, Carlos; Ibarra-Laclette, Enrique; Herrera-Estrella, Luis; Simpson, June

2009-01-01

Background Drought is one of the major constraints for plant productivity worldwide. Different mechanisms of drought-tolerance have been reported for several plant species including maize. However, the differences in global gene expression between drought-tolerant and susceptible genotypes and their relationship to physiological adaptations to drought are largely unknown. The study of the differences in global gene expression between tolerant and susceptible genotypes could provide important information to design more efficient breeding programs to produce maize varieties better adapted to water limiting conditions. Methodology/Principal Findings Changes in physiological responses and gene expression patterns were studied under drought stress and recovery in three Mexican maize landraces which included two drought tolerant (Cajete criollo and Michoacán 21) and one susceptible (85-2) genotypes. Photosynthesis, stomatal conductance, soil and leaf water potentials were monitored throughout the experiment and microarray analysis was carried out on transcripts obtained at 10 and 17 days following application of stress and after recovery irrigation. The two tolerant genotypes show more drastic changes in global gene expression which correlate with different physiological mechanisms of adaptation to drought. Differences in the kinetics and number of up- and down-regulated genes were observed between the tolerant and susceptible maize genotypes, as well as differences between the two tolerant genotypes. Interestingly, the most dramatic differences between the tolerant and susceptible genotypes were observed during recovery irrigation, suggesting that the tolerant genotypes activate mechanisms that allow more efficient recovery after a severe drought. Conclusions/Significance A correlation between levels of photosynthesis and transcription under stress was observed and differences in the number, type and expression levels of transcription factor families were also identified under drought and recovery between the three maize landraces. Gene expression analysis suggests that the drought tolerant landraces have a greater capacity to rapidly modulate more genes under drought and recovery in comparison to the susceptible landrace. Modulation of a greater number of differentially expressed genes of different TF gene families is an important characteristic of the tolerant genotypes. Finally, important differences were also noted between the tolerant landraces that underlie different mechanisms of achieving tolerance. PMID:19888455

In Utero Bisphenol A Concentration, Metabolism, and Global DNA Methylation Across Matched Placenta, Kidney, and Liver in the Human Fetus

PubMed Central

Nahar, Muna S.; Liao, Chunyang; Kannan, Kurunthachalam; Harris, Craig; Dolinoy, Dana C.

2014-01-01

While urine has been an easily accessible and feasible matrix for human biomonitoring, analytical measurements in internal tissues and organs can provide more accurate exposure assessments to understand disease etiology. This is especially important for the endocrine active compound, bisphenol A (BPA), where studies investigating internal doses at sensitive periods of human development are currently lacking. Herein, BPA concentrations, BPA-specific metabolizing enzyme gene expression, and global DNA methylation were characterized across three matched tissues from elective pregnancy terminations of 2nd trimester human fetuses: the placenta, liver, and kidney (N=12 each; N=36 total). Compared to liver (free: 0.54-50.5 ng/g), BPA concentrations were lower in matched placenta (<0.05-25.4 ng/g) and kidney (0.08-11.1 ng/g) specimens. BPA-specific metabolism gene expression of GUSB, UGT2B15, STS, and SULT1A1 differed across each tissue type; however, conjugation and deconjugation expression patterns were similar across the fetus. Average LINE1 and CCGG global methylation were 58.3 and 59.2% in placenta, 79.5 and 66.4% in fetal liver, and 77.9 and 77.0% in fetal kidney, with significant tissue-specific DNA methylation differences in both LINE1 (p-value <0.001) and CCGG content (p-value <0.001). Total BPA concentrations were positively associated with global methylation for the placenta only using the LINE1 assay (p-value: 0.002), suggesting organ-specific biological effects after fetal exposure. Utilizing sensitive human clinical specimens, results are informative for BPA toxicokinetics and toxicodynamics assessment in the developing human fetus. PMID:25434263

Acute and Chronic Electroconvulsive Seizures (ECS) Differentially Regulate the Expression of Epigenetic Machinery in the Adult Rat Hippocampus.

PubMed

Pusalkar, Madhavi; Ghosh, Shreya; Jaggar, Minal; Husain, Basma Fatima Anwar; Galande, Sanjeev; Vaidya, Vidita A

2016-09-01

Electroconvulsive seizure treatment is a fast-acting antidepressant therapy that evokes rapid transcriptional, neurogenic, and behavioral changes. Epigenetic mechanisms contribute to altered gene regulation, which underlies the neurogenic and behavioral effects of electroconvulsive seizure. We hypothesized that electroconvulsive seizure may modulate the expression of epigenetic machinery, thus establishing potential alterations in the epigenetic landscape. We examined the influence of acute and chronic electroconvulsive seizure on the gene expression of histone modifiers, namely histone acetyltransferases, histone deacetylases, histone methyltransferases, and histone (lysine) demethylases as well as DNA modifying enzymes, including DNA methyltransferases, DNA demethylases, and methyl-CpG-binding proteins in the hippocampi of adult male Wistar rats using quantitative real time-PCR analysis. Further, we examined the influence of acute and chronic electroconvulsive seizure on global and residue-specific histone acetylation and methylation levels within the hippocampus, a brain region implicated in the cellular and behavioral effects of electroconvulsive seizure. Acute and chronic electroconvulsive seizure induced a primarily unique, and in certain cases bidirectional, regulation of histone and DNA modifiers, and methyl-CpG-binding proteins, with an overlapping pattern of gene regulation restricted to Sirt4, Mll3, Jmjd3, Gadd45b, Tet2, and Tet3. Global histone acetylation and methylation levels were predominantly unchanged, with the exception of a significant decline in H3K9 acetylation in the hippocampus following chronic electroconvulsive seizure. Electroconvulsive seizure treatment evokes the transcriptional regulation of several histone and DNA modifiers, and methyl-CpG-binding proteins within the hippocampus, with a predominantly distinct pattern of regulation induced by acute and chronic electroconvulsive seizure. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Acute and Chronic Electroconvulsive Seizures (ECS) Differentially Regulate the Expression of Epigenetic Machinery in the Adult Rat Hippocampus

PubMed Central

Pusalkar, Madhavi; Ghosh, Shreya; Jaggar, Minal; Husain, Basma Fatima Anwar; Galande, Sanjeev

2016-01-01

Background: Electroconvulsive seizure treatment is a fast-acting antidepressant therapy that evokes rapid transcriptional, neurogenic, and behavioral changes. Epigenetic mechanisms contribute to altered gene regulation, which underlies the neurogenic and behavioral effects of electroconvulsive seizure. We hypothesized that electroconvulsive seizure may modulate the expression of epigenetic machinery, thus establishing potential alterations in the epigenetic landscape. Methods: We examined the influence of acute and chronic electroconvulsive seizure on the gene expression of histone modifiers, namely histone acetyltransferases, histone deacetylases, histone methyltransferases, and histone (lysine) demethylases as well as DNA modifying enzymes, including DNA methyltransferases, DNA demethylases, and methyl-CpG-binding proteins in the hippocampi of adult male Wistar rats using quantitative real time-PCR analysis. Further, we examined the influence of acute and chronic electroconvulsive seizure on global and residue-specific histone acetylation and methylation levels within the hippocampus, a brain region implicated in the cellular and behavioral effects of electroconvulsive seizure. Results: Acute and chronic electroconvulsive seizure induced a primarily unique, and in certain cases bidirectional, regulation of histone and DNA modifiers, and methyl-CpG-binding proteins, with an overlapping pattern of gene regulation restricted to Sirt4, Mll3, Jmjd3, Gadd45b, Tet2, and Tet3. Global histone acetylation and methylation levels were predominantly unchanged, with the exception of a significant decline in H3K9 acetylation in the hippocampus following chronic electroconvulsive seizure. Conclusions: Electroconvulsive seizure treatment evokes the transcriptional regulation of several histone and DNA modifiers, and methyl-CpG-binding proteins within the hippocampus, with a predominantly distinct pattern of regulation induced by acute and chronic electroconvulsive seizure. PMID:27207907

CO2 induced seawater acidification impacts sea urchin larval development II: gene expression patterns in pluteus larvae.

PubMed

Stumpp, M; Dupont, S; Thorndyke, M C; Melzner, F

2011-11-01

Extensive use of fossil fuels is leading to increasing CO(2) concentrations in the atmosphere and causes changes in the carbonate chemistry of the oceans which represents a major sink for anthropogenic CO(2). As a result, the oceans' surface pH is expected to decrease by ca. 0.4 units by the year 2100, a major change with potentially negative consequences for some marine species. Because of their carbonate skeleton, sea urchins and their larval stages are regarded as likely to be one of the more sensitive taxa. In order to investigate sensitivity of pre-feeding (2 days post-fertilization) and feeding (4 and 7 days post-fertilization) pluteus larvae, we raised Strongylocentrotus purpuratus embryos in control (pH 8.1 and pCO(2) 41 Pa e.g. 399 μatm) and CO(2) acidified seawater with pH of 7.7 (pCO(2) 134 Pa e.g. 1318 μatm) and investigated growth, calcification and survival. At three time points (day 2, day 4 and day 7 post-fertilization), we measured the expression of 26 representative genes important for metabolism, calcification and ion regulation using RT-qPCR. After one week of development, we observed a significant difference in growth. Maximum differences in size were detected at day 4 (ca. 10% reduction in body length). A comparison of gene expression patterns using PCA and ANOSIM clearly distinguished between the different age groups (two-way ANOSIM: Global R=1) while acidification effects were less pronounced (Global R=0.518). Significant differences in gene expression patterns (ANOSIM R=0.938, SIMPER: 4.3% difference) were also detected at day 4 leading to the hypothesis that differences between CO(2) treatments could reflect patterns of expression seen in control experiments of a younger larva and thus a developmental artifact rather than a direct CO(2) effect. We found an up regulation of metabolic genes (between 10%and 20% in ATP-synthase, citrate synthase, pyruvate kinase and thiolase at day 4) and down regulation of calcification related genes (between 23% and 36% in msp130, SM30B, and SM50 at day 4). Ion regulation was mainly impacted by up regulation of Na(+)/K(+)-ATPase at day 4 (15%) and down regulation of NHE3 at day 4 (45%). We conclude that in studies in which a stressor induces an alteration in the speed of development, it is crucial to employ experimental designs with a high time resolution in order to correct for developmental artifacts. This helps prevent misinterpretation of stressor effects on organism physiology. Copyright © 2011 Elsevier Inc. All rights reserved.

Reactivation of Rate Remapping in CA3.

PubMed

Schwindel, C Daniela; Navratilova, Zaneta; Ali, Karim; Tatsuno, Masami; McNaughton, Bruce L

2016-09-07

The hippocampus is thought to contribute to episodic memory by creating, storing, and reactivating patterns that are unique to each experience, including different experiences that happen at the same location. Hippocampus can combine spatial and contextual/episodic information using a dual coding scheme known as "global" and "rate" remapping. Global remapping selects which set of neurons can activate at a given location. Rate remapping readjusts the firing rates of this set depending on current experience, thus expressing experience-unique patterns at each location. But can the experience-unique component be retrieved spontaneously? Whereas reactivation of recent, spatially selective patterns in hippocampus is well established, it is never perfect, raising the issue of whether the experiential component might be absent. This question is key to the hypothesis that hippocampus can assist memory consolidation by reactivating and broadcasting experience-specific "index codes" to neocortex. In CA3, global remapping exhibits attractor-like dynamics, whereas rate remapping apparently does not, leading to the hypothesis that only the former can be retrieved associatively and casting doubt on the general consolidation hypothesis. Therefore, we studied whether the rate component is reactivated spontaneously during sleep. We conducted neural ensemble recordings from CA3 while rats ran on a circular track in different directions (in different sessions) and while they slept. It was shown previously that the two directions of running result in strong rate remapping. During sleep, the most recent rate distribution was reactivated preferentially. Therefore, CA3 can retrieve patterns spontaneously that are unique to both the location and the content of recent experience. The hippocampus is required for memory of events and their spatial contexts. The primary correlate of hippocampal activity is location in space, but multiple memories can occur in the same location. To be useful for distinguishing these memories, the hippocampus must be able, not only to express, but also to retrieve both spatial and nonspatial information about events. Whether it can retrieve nonspatial information has been challenged recently. We exposed rats to two different experiences (running in different directions) in the same locations and showed that even the nonspatial components of hippocampal cell firing are reactivated spontaneously during sleep, supporting the conclusion that both types of information about a recent experience can be retrieved. Copyright © 2016 the authors 0270-6474/16/369342-09$15.00/0.

Core Canonical Pathways Involved in Developing Human Glioblastoma Multiforme (GBM).

PubMed

Ghosh, Somiranjan; Dutta, Sisir; Thorne, Gabriel; Boston, Ava; Barfield, Alexis; Banerjee, Narendra; Walker, Rayshawn; Banerjee, Hirendra Nath

2017-02-01

Glioblastoma multiforme (GBM) is the most common and aggressive type of the primary brain tumors with pathologic hallmarks of necrosis and vascular proliferation. The diagnosis of GBM is currently mostly based on histological examination of brain tumor tissues, after radiological characterization and surgical biopsy. The ability to characterize tumors comprehensively at the molecular level raises the possibility that diagnosis can be made based on molecular profiling with or without histological examination, rather than solely on histological phenotype. The development of novel genomic and proteomic techniques will foster in the identification of such diagnostic and prognostic molecular markers. We analyzed the global differential gene expression of a GBM cell line HTB15 in comparison to normal human Astrocytes, and established a few canonical pathways that are important in determining the molecular mechanisms of cancer using global gene expression microarray, coupled with the Ingenuity Pathway Analysis ( IPA ®). Overall, we revealed a discrete gene expression profile in the experimental model that resembled progression of GBM cancer. The canonical pathway analysis showed the involvement of genes that differentially expressed in such a disease condition that included Inositol pathway, Polo like kinases, nNOS signaling , and Tetrapyrrole biosynthesis . Our findings established that the gene expression pattern of this dreaded brain cancer will probably help the cancer research community by finding out newer therapeutic strategies to combat this dreaded cancer type that leads to the identification of high-risk population in this category, with almost hundred percent mortality rate.

The vent microbiome: patterns and drivers

NASA Astrophysics Data System (ADS)

Pachiadaki, M.

2015-12-01

Microbial processes within deep-sea hydrothermal vents affect the global biogeochemical cycles. Still, there are significant gaps in our understanding of the microbiology and the biogeochemistry of deep-sea hydrothermal systems. Vents differ in temperature, host rock composition and fluid chemistry; factors that are hypothesized to shape the distribution of the microbial communities, their metabolic capabilities and their activities. Using large-scale single cell genomics, we obtained insights into the genomic content of several linkages of a diffuse flow vent. The genomes show high metabolic versatility. Sulfur oxidation appears to be predominant but there is the potential of using a variety of e- donors and acceptors to obtain energy. To further assess the ecological importance of the vent auto- and heterotrophs, the global biogeography of the analyzed lineages will be investigated by fragment recruitment of metagenomes produced from the same site as well as other hydrothermal systems. Metatranscriptomic and metaproteomic data will be integrated to examine the expression of the predominant metabolic pathways and thus the main energy sources driving chemoautotrophic production. The comparative analysis of the key players and associated pathways among various vent sites that differ in physicochemical characteristics is anticipated to decipher the patterns and drivers of the global dispersion and the local diversification of the vent microbiome.

Global increase and geographic convergence in antibiotic consumption between 2000 and 2015

PubMed Central

Van Boeckel, Thomas P.; Martinez, Elena M.; Pant, Suraj; Gandra, Sumanth; Levin, Simon A.; Goossens, Herman

2018-01-01

Tracking antibiotic consumption patterns over time and across countries could inform policies to optimize antibiotic prescribing and minimize antibiotic resistance, such as setting and enforcing per capita consumption targets or aiding investments in alternatives to antibiotics. In this study, we analyzed the trends and drivers of antibiotic consumption from 2000 to 2015 in 76 countries and projected total global antibiotic consumption through 2030. Between 2000 and 2015, antibiotic consumption, expressed in defined daily doses (DDD), increased 65% (21.1–34.8 billion DDDs), and the antibiotic consumption rate increased 39% (11.3–15.7 DDDs per 1,000 inhabitants per day). The increase was driven by low- and middle-income countries (LMICs), where rising consumption was correlated with gross domestic product per capita (GDPPC) growth (P = 0.004). In high-income countries (HICs), although overall consumption increased modestly, DDDs per 1,000 inhabitants per day fell 4%, and there was no correlation with GDPPC. Of particular concern was the rapid increase in the use of last-resort compounds, both in HICs and LMICs, such as glycylcyclines, oxazolidinones, carbapenems, and polymyxins. Projections of global antibiotic consumption in 2030, assuming no policy changes, were up to 200% higher than the 42 billion DDDs estimated in 2015. Although antibiotic consumption rates in most LMICs remain lower than in HICs despite higher bacterial disease burden, consumption in LMICs is rapidly converging to rates similar to HICs. Reducing global consumption is critical for reducing the threat of antibiotic resistance, but reduction efforts must balance access limitations in LMICs and take account of local and global resistance patterns. PMID:29581252

Gene expression profiles of Arabidopsis Cvi seeds during dormancy cycling indicate a common underlying dormancy control mechanism.

PubMed

Cadman, Cassandra S C; Toorop, Peter E; Hilhorst, Henk W M; Finch-Savage, William E

2006-06-01

Physiologically dormant seeds, like those of Arabidopsis, will cycle through dormant states as seasons change until the environment is favourable for seedling establishment. This phenomenon is widespread in the plant kingdom, but has not been studied at the molecular level. Full-genome microarrays were used for a global transcript analysis of Arabidopsis thaliana (accession Cvi) seeds in a range of dormant and dry after-ripened states during cycling. Principal component analysis of the expression patterns observed showed that they differed in newly imbibed primary dormant seeds, as commonly used in experimental studies, compared with those in the maintained primary and secondary dormant states that exist during cycling. Dormant and after-ripened seeds appear to have equally active although distinct gene expression programmes, dormant seeds having greatly reduced gene expression associated with protein synthesis, potentially controlling the completion of germination. A core set of 442 genes were identified that had higher expression in all dormant states compared with after-ripened states. Abscisic acid (ABA) responsive elements were significantly over-represented in this set of genes the expression of which was enhanced when multiple copies of the elements were present. ABA regulation of dormancy was further supported by expression patterns of key genes in ABA synthesis/catabolism, and dormancy loss in the presence of fluridone. The data support an ABA-gibberelic acid hormone balance mechanism controlling cycling through dormant states that depends on synthetic and catabolic pathways of both hormones. Many of the most highly expressed genes in dormant states were stress-related even in the absence of abiotic stress, indicating that ABA, stress and dormancy responses overlap significantly at the transcriptome level.

Global gene expression analysis of apple fruit development from the floral bud to ripe fruit

PubMed Central

Janssen, Bart J; Thodey, Kate; Schaffer, Robert J; Alba, Rob; Balakrishnan, Lena; Bishop, Rebecca; Bowen, Judith H; Crowhurst, Ross N; Gleave, Andrew P; Ledger, Susan; McArtney, Steve; Pichler, Franz B; Snowden, Kimberley C; Ward, Shayna

2008-01-01

Background Apple fruit develop over a period of 150 days from anthesis to fully ripe. An array representing approximately 13000 genes (15726 oligonucleotides of 45–55 bases) designed from apple ESTs has been used to study gene expression over eight time points during fruit development. This analysis of gene expression lays the groundwork for a molecular understanding of fruit growth and development in apple. Results Using ANOVA analysis of the microarray data, 1955 genes showed significant changes in expression over this time course. Expression of genes is coordinated with four major patterns of expression observed: high in floral buds; high during cell division; high when starch levels and cell expansion rates peak; and high during ripening. Functional analysis associated cell cycle genes with early fruit development and three core cell cycle genes are significantly up-regulated in the early stages of fruit development. Starch metabolic genes were associated with changes in starch levels during fruit development. Comparison with microarrays of ethylene-treated apple fruit identified a group of ethylene induced genes also induced in normal fruit ripening. Comparison with fruit development microarrays in tomato has been used to identify 16 genes for which expression patterns are similar in apple and tomato and these genes may play fundamental roles in fruit development. The early phase of cell division and tissue specification that occurs in the first 35 days after pollination has been associated with up-regulation of a cluster of genes that includes core cell cycle genes. Conclusion Gene expression in apple fruit is coordinated with specific developmental stages. The array results are reproducible and comparisons with experiments in other species has been used to identify genes that may play a fundamental role in fruit development. PMID:18279528

Global gene expression analysis of apple fruit development from the floral bud to ripe fruit.

PubMed

Janssen, Bart J; Thodey, Kate; Schaffer, Robert J; Alba, Rob; Balakrishnan, Lena; Bishop, Rebecca; Bowen, Judith H; Crowhurst, Ross N; Gleave, Andrew P; Ledger, Susan; McArtney, Steve; Pichler, Franz B; Snowden, Kimberley C; Ward, Shayna

2008-02-17

Apple fruit develop over a period of 150 days from anthesis to fully ripe. An array representing approximately 13000 genes (15726 oligonucleotides of 45-55 bases) designed from apple ESTs has been used to study gene expression over eight time points during fruit development. This analysis of gene expression lays the groundwork for a molecular understanding of fruit growth and development in apple. Using ANOVA analysis of the microarray data, 1955 genes showed significant changes in expression over this time course. Expression of genes is coordinated with four major patterns of expression observed: high in floral buds; high during cell division; high when starch levels and cell expansion rates peak; and high during ripening. Functional analysis associated cell cycle genes with early fruit development and three core cell cycle genes are significantly up-regulated in the early stages of fruit development. Starch metabolic genes were associated with changes in starch levels during fruit development. Comparison with microarrays of ethylene-treated apple fruit identified a group of ethylene induced genes also induced in normal fruit ripening. Comparison with fruit development microarrays in tomato has been used to identify 16 genes for which expression patterns are similar in apple and tomato and these genes may play fundamental roles in fruit development. The early phase of cell division and tissue specification that occurs in the first 35 days after pollination has been associated with up-regulation of a cluster of genes that includes core cell cycle genes. Gene expression in apple fruit is coordinated with specific developmental stages. The array results are reproducible and comparisons with experiments in other species has been used to identify genes that may play a fundamental role in fruit development.

Inferring the Limit Behavior of Some Elementary Cellular Automata

NASA Astrophysics Data System (ADS)

Ruivo, Eurico L. P.; de Oliveira, Pedro P. B.

Cellular automata locally define dynamical systems, discrete in space, time and in the state variables, capable of displaying arbitrarily complex global emergent behavior. One core question in the study of cellular automata refers to their limit behavior, that is, to the global dynamical features in an infinite time evolution. Previous works have shown that for finite time evolutions, the dynamics of one-dimensional cellular automata can be described by regular languages and, therefore, by finite automata. Such studies have shown the existence of growth patterns in the evolution of such finite automata for some elementary cellular automata rules and also inferred the limit behavior of such rules based upon the growth patterns; however, the results on the limit behavior were obtained manually, by direct inspection of the structures that arise during the time evolution. Here we present the formalization of an automatic method to compute such structures. Based on this, the rules of the elementary cellular automata space were classified according to the existence of a growth pattern in their finite automata. Also, we present a method to infer the limit graph of some elementary cellular automata rules, derived from the analysis of the regular expressions that describe their behavior in finite time. Finally, we analyze some attractors of two rules for which we could not compute the whole limit set.

Gene profiling, biomarkers and pathways characterizing HCV-related hepatocellular carcinoma

PubMed Central

De Giorgi, Valeria; Monaco, Alessandro; Worchech, Andrea; Tornesello, MariaLina; Izzo, Francesco; Buonaguro, Luigi; Marincola, Francesco M; Wang, Ena; Buonaguro, Franco M

2009-01-01

Background Hepatitis C virus (HCV) infection is a major cause of hepatocellular carcinoma (HCC) worldwide. The molecular mechanisms of HCV-induced hepatocarcinogenesis are not yet fully elucidated. Besides indirect effects as tissue inflammation and regeneration, a more direct oncogenic activity of HCV can be postulated leading to an altered expression of cellular genes by early HCV viral proteins. In the present study, a comparison of gene expression patterns has been performed by microarray analysis on liver biopsies from HCV-positive HCC patients and HCV-negative controls. Methods Gene expression profiling of liver tissues has been performed using a high-density microarray containing 36'000 oligos, representing 90% of the human genes. Samples were obtained from 14 patients affected by HCV-related HCC and 7 HCV-negative non-liver-cancer patients, enrolled at INT in Naples. Transcriptional profiles identified in liver biopsies from HCC nodules and paired non-adjacent non-HCC liver tissue of the same HCV-positive patients were compared to those from HCV-negative controls by the Cluster program. The pathway analysis was performed using the BRB-Array- Tools based on the "Ingenuity System Database". Significance threshold of t-test was set at 0.001. Results Significant differences were found between the expression patterns of several genes falling into different metabolic and inflammation/immunity pathways in HCV-related HCC tissues as well as the non-HCC counterpart compared to normal liver tissues. Only few genes were found differentially expressed between HCV-related HCC tissues and paired non-HCC counterpart. Conclusion In this study, informative data on the global gene expression pattern of HCV-related HCC and non-HCC counterpart, as well as on their difference with the one observed in normal liver tissues have been obtained. These results may lead to the identification of specific biomarkers relevant to develop tools for detection, diagnosis, and classification of HCV-related HCC. PMID:19821982

Focal exposure of limited lung volumes to high-dose irradiation down-regulated organ development-related functions and up-regulated the immune response in mouse pulmonary tissues.

PubMed

Kim, Bu-Yeo; Jin, Hee; Lee, Yoon-Jin; Kang, Ga-Young; Cho, Jaeho; Lee, Yun-Sil

2016-01-27

Despite the emergence of stereotactic body radiotherapy (SBRT) for treatment of medically inoperable early-stage non-small-cell lung cancer patients, the molecular effects of focal exposure of limited lung volumes to high-dose radiation have not been fully characterized. This study was designed to identify molecular changes induced by focal high-dose irradiation using a mouse model of SBRT. Central areas of the mouse left lung were focally-irradiated (3 mm in diameter) with a single high-dose of radiation (90 Gy). Temporal changes in gene expression in the irradiated and non-irradiated neighboring lung regions were analyzed by microarray. For comparison, the long-term effect (12 months) of 20 Gy radiation on a diffuse region of lung was also measured. The majority of genes were down-regulated in the focally-irradiated lung areas at 2 to 3 weeks after irradiation. This pattern of gene expression was clearly different than gene expression in the diffuse region of lungs exposed to low-dose radiation. Ontological and pathway analyses indicated these down-regulated genes were mainly associated with organ development. Although the number was small, genes that were up-regulated after focal irradiation were associated with immune-related functions. The temporal patterns of gene expression and the associated biological functions were also similar in non-irradiated neighboring lung regions, although statistical significance was greatly reduced when compared with those from focally-irradiated areas of the lung. From network analysis of temporally regulated genes, we identified inter-related modules associated with diverse functions, including organ development and the immune response, in both the focally-irradiated regions and non-irradiated neighboring lung regions. Focal exposure of lung tissue to high-dose radiation induced expression of genes associated with organ development and the immune response. This pattern of gene expression was also observed in non-irradiated neighboring areas of lung tissue, indicating a global lung response to focal high-dose irradiation.

Neural crest development and craniofacial morphogenesis is coordinated by nitric oxide and histone acetylation

PubMed Central

Kong, Yawei; Grimaldi, Michael; Curtin, Eugene; Dougherty, Max; Kaufman, Charles; White, Richard M.; Zon, Leonard I.; Liao, Eric C.

2015-01-01

Cranial neural crest (CNC) cells are patterned and coalesce to facial prominences that undergo convergence and extension to generate the craniofacial form. We applied a chemical genetics approach to identify pathways that regulate craniofacial development during embryogenesis. Treatment with the nitric oxide synthase inhibitor TRIM abrogated first pharyngeal arch structures and induced ectopic ceratobranchial formation. TRIM promoted a progenitor CNC fate and inhibited chondrogenic differentiation, which were mediated through impaired nitric oxide (NO) production without appreciable effect on global protein S-nitrosylation. Instead, TRIM perturbed hox gene patterning and caused histone hypoacetylation. Rescue of TRIM phenotype was achieved with over-expression of histone acetyltransferase kat6a, inhibition of histone deacetylase, and complimentary NO. These studies demonstrate that NO signaling and histone acetylation are coordinated mechanisms that regulate CNC patterning, differentiation and convergence during craniofacial morphogenesis. PMID:24684905

Sedimentary evidence for enhanced hydrological cycling in response to rapid carbon release during the early Toarcian oceanic anoxic event

NASA Astrophysics Data System (ADS)

Izumi, Kentaro; Kemp, David B.; Itamiya, Shoma; Inui, Mutsuko

2018-01-01

A pronounced excursion in the carbon-isotope composition of biospheric carbon and coeval seawater warming during the early Toarcian (∼183 Ma) has been linked to the large-scale transfer of 12C-enriched carbon to the oceans and atmosphere. A European bias in the distribution of available data means that the precise pattern, tempo and global expression of this carbon cycle perturbation, and the associated environmental responses, remain uncertain. Here, we present a new cm-scale terrestrial-dominated carbon-isotope record through an expanded lower Toarcian section from Japan that displays a negative excursion pattern similar to marine and terrestrial carbon-isotope records documented from Europe. These new data suggest that 12C-enriched carbon was added to the biosphere in at least one rapid, millennial-scale pulse. Sedimentological analysis indicates a close association between the carbon-isotope excursion and high-energy sediment transport and enhanced fluvial discharge. Together, these data support the hypothesis that a sudden strengthening of the global hydrological cycle occurred in direct and immediate response to rapid carbon release and atmospheric warming.

Distinct mutations in yeast TAF(II)25 differentially affect the composition of TFIID and SAGA complexes as well as global gene expression patterns.

PubMed

Kirschner, Doris B; vom Baur, Elmar; Thibault, Christelle; Sanders, Steven L; Gangloff, Yann-Gaël; Davidson, Irwin; Weil, P Anthony; Tora, Làszlò

2002-05-01

The RNA polymerase II transcription factor TFIID, composed of the TATA-binding protein (TBP) and TBP-associated factors (TAF(II)s), nucleates preinitiation complex formation at protein-coding gene promoters. SAGA, a second TAF(II)-containing multiprotein complex, is involved in transcription regulation in Saccharomyces cerevisiae. One of the essential protein components common to SAGA and TFIID is yTAF(II)25. We define a minimal evolutionarily conserved 91-amino-acid region of TAF(II)25 containing a histone fold domain that is necessary and sufficient for growth in vivo. Different temperature-sensitive mutations of yTAF(II)25 or chimeras with the human homologue TAF(II)30 arrested cell growth at either the G(1) or G(2)/M cell cycle phase and displayed distinct phenotypic changes and gene expression patterns. Immunoprecipitation studies revealed that TAF(II)25 mutation-dependent gene expression and phenotypic changes correlated at least partially with the integrity of SAGA and TFIID. Genome-wide expression analysis revealed that the five TAF(II)25 temperature-sensitive mutant alleles individually affect the expression of between 18 and 33% of genes, whereas taken together they affect 64% of all class II genes. Thus, different yTAF(II)25 mutations induce distinct phenotypes and affect the regulation of different subsets of genes, demonstrating that no individual TAF(II) mutant allele reflects the full range of its normal functions.

Multiscale Spatial Modeling of Human Exposure from Local Sources to Global Intake.

PubMed

Wannaz, Cedric; Fantke, Peter; Jolliet, Olivier

2018-01-16

Exposure studies, used in human health risk and impact assessments of chemicals, are largely performed locally or regionally. It is usually not known how global impacts resulting from exposure to point source emissions compare to local impacts. To address this problem, we introduce Pangea, an innovative multiscale, spatial multimedia fate and exposure assessment model. We study local to global population exposure associated with emissions from 126 point sources matching locations of waste-to-energy plants across France. Results for three chemicals with distinct physicochemical properties are expressed as the evolution of the population intake fraction through inhalation and ingestion as a function of the distance from sources. For substances with atmospheric half-lives longer than a week, less than 20% of the global population intake through inhalation (median of 126 emission scenarios) can occur within a 100 km radius from the source. This suggests that, by neglecting distant low-level exposure, local assessments might only account for fractions of global cumulative intakes. We also study ∼10 000 emission locations covering France more densely to determine per chemical and exposure route which locations minimize global intakes. Maps of global intake fractions associated with each emission location show clear patterns associated with population and agriculture production densities.

Plant Bio-Wars: Maize Protein Networks Reveal Tissue-Specific Defense Strategies in Response to a Root Herbivore.

PubMed

Castano-Duque, Lina; Helms, Anjel; Ali, Jared Gregory; Luthe, Dawn S

2018-06-21

In this study we examined global changes in protein expression in both roots and leaves of maize plants attacked by the root herbivore, Western corn rootworm (WCR, Diabrotica virgifera virgifera). The changes in protein expression Are indicative of metabolic changes during WCR feeding that enable the plant to defend itself. This is one of the first studies to look above- and below-ground at global protein expression patterns of maize plants grown in soil and infested with a root herbivore. We used advanced proteomic and network analyses to identify metabolic pathways that contribute to global defenses deployed by the insect resistant maize genotype, Mp708, infested with WCR. Using proteomic analysis, 4878 proteins in roots and leaves were detected and of these 863 showed significant changes of abundance during WCR infestation. Protein abundance patterns were analyzed using hierarchical clustering, protein correlation and protein-protein interaction networks. All three data analysis pipelines showed that proteins such as jasmonic acid biosynthetic enzymes, serine proteases, protease inhibitors, proteins involved in biosynthesis and signaling of ethylene, and enzymes producing reactive oxygen species and isopentenyl pyrophosphate, a precursor for volatile production, were upregulated in roots during WCR infestation. In leaves, highly abundant proteins were involved in signal perception suggesting activation of systemic signaling. We conclude that these protein networks contribute to the overall herbivore defense mechanisms in Mp708. Because the plants were grown in potting mix and not sterilized sand, we found that both microbial and insect defense-related proteins were present in the roots. The presence of the high constitutive levels of reduced ascorbate in roots and benzothiazole in the root volatile profiles suggest a tight tri-trophic interaction among the plant, soil microbiomes and WCR-infested roots suggesting that defenses against insects coexist with defenses against bacteria and fungi due to the interaction between roots and soil microbiota. In this study, which is one of the most complete descriptions of plant responses to root-feeding herbivore, we established an analysis pipeline for proteomics data that includes network biology that can be used with different types of "omics" data from a variety of organisms.

Proteomic analysis of fibroblastema formation in regenerating hind limbs of Xenopus laevis froglets and comparison to axolotl

PubMed Central

2014-01-01

Background To gain insight into what differences might restrict the capacity for limb regeneration in Xenopus froglets, we used High Performance Liquid Chromatography (HPLC)/double mass spectrometry to characterize protein expression during fibroblastema formation in the amputated froglet hindlimb, and compared the results to those obtained previously for blastema formation in the axolotl limb. Results Comparison of the Xenopus fibroblastema and axolotl blastema revealed several similarities and significant differences in proteomic profiles. The most significant similarity was the strong parallel down regulation of muscle proteins and enzymes involved in carbohydrate metabolism. Regenerating Xenopus limbs differed significantly from axolotl regenerating limbs in several ways: deficiency in the inositol phosphate/diacylglycerol signaling pathway, down regulation of Wnt signaling, up regulation of extracellular matrix (ECM) proteins and proteins involved in chondrocyte differentiation, lack of expression of a key cell cycle protein, ecotropic viral integration site 5 (EVI5), that blocks mitosis in the axolotl, and the expression of several patterning proteins not seen in the axolotl that may dorsalize the fibroblastema. Conclusions We have characterized global protein expression during fibroblastema formation after amputation of the Xenopus froglet hindlimb and identified several differences that lead to signaling deficiency, failure to retard mitosis, premature chondrocyte differentiation, and failure of dorsoventral axial asymmetry. These differences point to possible interventions to improve blastema formation and pattern formation in the froglet limb. PMID:25063185

Transcriptome analysis of Vibrio parahaemolyticus in type III secretion system 1 inducing conditions

PubMed Central

Nydam, Seth D.; Shah, Devendra H.; Call, Douglas R.

2014-01-01

Vibrio parahaemolyticus is an emerging bacterial pathogen capable of causing inflammatory gastroenteritis, wound infections, and septicemia. As a food-borne illness, infection is most frequently associated with the consumption of raw or undercooked seafood, particularly shellfish. It is the primary cause of Vibrio-associated food-borne illness in the United States and the leading cause of food-borne illness in Japan. The larger of its two chromosomes harbors a set of genes encoding type III section system 1 (T3SS1), a virulence factor present in all V. parahaemolyticus strains that is similar to the Yersinia ysc T3SS. T3SS1 translocates effector proteins into eukaryotic cells where they induce changes to cellular physiology and modulate host-pathogen interactions. T3SS1 is also responsible for cytotoxicity toward several different cultured cell lines as well as mortality in a mouse model. Herein we used RNA-seq to obtain global transcriptome patterns of V. parahaemolyticus under conditions that either induce [growth in Dulbecco's Modified Eagle Medium (DMEM) media, in trans expression of transcriptional regulator exsA] or repress T3SS1 expression (growth in LB-S media, in trans exsD expression) and during infection of HeLa cells over time. Comparative transcriptomic analysis demonstrated notable differences in the expression patterns under inducing conditions and was also used to generate an expression profile of V. parahaemolyticus during infection of HeLa cells. In addition, we identified several new genes that are associated with T3SS1 expression and may warrant further study. PMID:24478989

Switch-like reprogramming of gene expression after fusion of multinucleate plasmodial cells of two Physarum polycephalum sporulation mutants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walter, Pauline; Hoffmann, Xenia-Katharina; Ebeling, Britta

2013-05-24

Highlights: •We investigate reprogramming of gene expression in multinucleate single cells. •Cells of two differentiation control mutants are fused. •Fused cells proceed to alternative gene expression patterns. •The population of nuclei damps stochastic fluctuations in gene expression. •Dynamic processes of cellular reprogramming can be observed by repeated sampling of a cell. -- Abstract: Nonlinear dynamic processes involving the differential regulation of transcription factors are considered to impact the reprogramming of stem cells, germ cells, and somatic cells. Here, we fused two multinucleate plasmodial cells of Physarum polycephalum mutants defective in different sporulation control genes while being in different physiological states.more » The resulting heterokaryons established one of two significantly different expression patterns of marker genes while the plasmodial halves that were fused to each other synchronized spontaneously. Spontaneous synchronization suggests that switch-like control mechanisms spread over and finally control the entire plasmodium as a result of cytoplasmic mixing. Regulatory molecules due to the large volume of the vigorously streaming cytoplasm will define concentrations in acting on the population of nuclei and in the global setting of switches. Mixing of a large cytoplasmic volume is expected to damp stochasticity when individual nuclei deliver certain RNAs at low copy number into the cytoplasm. We conclude that spontaneous synchronization, the damping of molecular noise in gene expression by the large cytoplasmic volume, and the option to take multiple macroscopic samples from the same plasmodium provide unique options for studying the dynamics of cellular reprogramming at the single cell level.« less

Impacts of radiation management techniques on the North Atlantic Oscillation

NASA Astrophysics Data System (ADS)

Adakudlu, Muralidhar; Helge Otterå, Odd; Tjiputra, Jerry; Muri, Helene; Grini, Alf; Schulz, Michael

2017-04-01

The effectiveness of various climate engineering techniques in limiting the global warming signal to reasonable levels has been the topic of state-of-the-art research on climate change. Using an Earth system model, we show that these techniques have the potential to bring down the high CO2 concentration climate in RCP8.5 to a moderate climate similar to RCP4.5 in terms of global temperature. Nevertheless, their influence on the regional aspects of atmospheric circulation is not clear. The regional circulation patterns in the atmosphere are largely characterized by the natural variability modes, such as the North Atlantic Oscillation (NAO). In this study, we assess the impacts of three radiation managment techniques, namely, Stratospheric Aerosol Injection (SAI), Marine Sky Brightening (MSB) and Cirrus Cloud Thinning (CCT), on the structure and features of the NAO. The results indicate an east-northeastward shift as well as intensification of the NAO spatial pattern in the global warming scenarios of RCP4.5 and RCP8.5, with the signal being most intense in the latter. The climate engineering forcings when applied to the RCP8.5 case tend to reduce the strength of the NAO with little impact on its position. The CCT case appears to have the maximum effect on the NAO signal. The patterns of cloud radiative forcing, expressed as the difference between net radiative forcing at TOA under average conditions and clear sky conditions, reveal a northeastward shift of the radiative heating in the north Atlantic region. This implies a possible link between the changes in the NAO signal and the cloud radiative forcing.

Global patterns of groundwater table depth.

PubMed

Fan, Y; Li, H; Miguez-Macho, G

2013-02-22

Shallow groundwater affects terrestrial ecosystems by sustaining river base-flow and root-zone soil water in the absence of rain, but little is known about the global patterns of water table depth and where it provides vital support for land ecosystems. We present global observations of water table depth compiled from government archives and literature, and fill in data gaps and infer patterns and processes using a groundwater model forced by modern climate, terrain, and sea level. Patterns in water table depth explain patterns in wetlands at the global scale and vegetation gradients at regional and local scales. Overall, shallow groundwater influences 22 to 32% of global land area, including ~15% as groundwater-fed surface water features and 7 to 17% with the water table or its capillary fringe within plant rooting depths.

Temporal Patterns of Happiness and Information in a Global Social Network: Hedonometrics and Twitter

PubMed Central

Dodds, Peter Sheridan; Harris, Kameron Decker; Kloumann, Isabel M.; Bliss, Catherine A.; Danforth, Christopher M.

2011-01-01

Individual happiness is a fundamental societal metric. Normally measured through self-report, happiness has often been indirectly characterized and overshadowed by more readily quantifiable economic indicators such as gross domestic product. Here, we examine expressions made on the online, global microblog and social networking service Twitter, uncovering and explaining temporal variations in happiness and information levels over timescales ranging from hours to years. Our data set comprises over 46 billion words contained in nearly 4.6 billion expressions posted over a 33 month span by over 63 million unique users. In measuring happiness, we construct a tunable, real-time, remote-sensing, and non-invasive, text-based hedonometer. In building our metric, made available with this paper, we conducted a survey to obtain happiness evaluations of over 10,000 individual words, representing a tenfold size improvement over similar existing word sets. Rather than being ad hoc, our word list is chosen solely by frequency of usage, and we show how a highly robust and tunable metric can be constructed and defended. PMID:22163266

Temporal patterns of happiness and information in a global social network: hedonometrics and Twitter.

PubMed

Dodds, Peter Sheridan; Harris, Kameron Decker; Kloumann, Isabel M; Bliss, Catherine A; Danforth, Christopher M

2011-01-01

Individual happiness is a fundamental societal metric. Normally measured through self-report, happiness has often been indirectly characterized and overshadowed by more readily quantifiable economic indicators such as gross domestic product. Here, we examine expressions made on the online, global microblog and social networking service Twitter, uncovering and explaining temporal variations in happiness and information levels over timescales ranging from hours to years. Our data set comprises over 46 billion words contained in nearly 4.6 billion expressions posted over a 33 month span by over 63 million unique users. In measuring happiness, we construct a tunable, real-time, remote-sensing, and non-invasive, text-based hedonometer. In building our metric, made available with this paper, we conducted a survey to obtain happiness evaluations of over 10,000 individual words, representing a tenfold size improvement over similar existing word sets. Rather than being ad hoc, our word list is chosen solely by frequency of usage, and we show how a highly robust and tunable metric can be constructed and defended.

Dietary vitamin E deficiency does not affect global and specific DNA methylation patterns in rat liver.

PubMed

Fischer, Alexandra; Gaedicke, Sonja; Frank, Jan; Döring, Frank; Rimbach, Gerald

2010-10-01

The aim of the present study was to determine the effects of a 6-month dietary vitamin E (VE) deficiency on DNA methylation and gene expression in rat liver. Two enzymes, 5-α-steroid reductase type 1 (SRD5A1) and the regulatory subunit of γ-glutamylcysteinyl synthetase (GCLM), which are differentially expressed on the mRNA level, were analysed for promoter methylation in putative cytosine-phospho-guanine (CpG) island regions located at the 5' end using base-specific cleavage and matrix-assisted laser desorption ionisation time-of-flight MS. A twofold increase in the mRNA level of SRD5A1 gene and a twofold decrease in the mRNA level of GCLM gene in VE-deficient animals were not associated with different CpG methylation of the analysed promoter region. Furthermore, global DNA methylation was not significantly different in these two groups. Thus, the present results indicate that the VE-induced regulation of SRD5A1 and GCLM in rat liver is not directly mediated by changes in promoter DNA methylation.

Global expression pattern comparison between low phosphorus insensitive 4 and WT Arabidopsis reveals an important role of reactive oxygen species and jasmonic acid in the root tip response to phosphate starvation

PubMed Central

Chacón-López, Alejandra; Ibarra-Laclette, Enrique; Sánchez-Calderón, Lenin; Gutiérrez-Alanís, Dolores

2011-01-01

Plants are exposed to several biotic and abiotic stresses. A common environmental stress that plants have to face both in natural and agricultural ecosystems that impacts both its growth and development is low phosphate (Pi) availability. There has been an important progress in the knowledge of the molecular mechanisms by which plants cope with Pi deficiency. However, the mechanisms that mediate alterations in the architecture of the Arabidopsis root system responses to Pi starvation are still largely unknown. One of the most conspicuous developmental effects of low Pi on the Arabidopsis root system is the inhibition of primary root growth that is accompanied by loss of root meristematic activity. To identify signalling pathways potentially involved in the Arabidpsis root meristem response to Pi-deprivation, here we report the global gene expression analysis of the root tip of wild type and low phosphorus insensitive4 (lpi4) mutant grown under Pi limiting conditions. Differential gene expression analysis and physiological experiments show that changes in the redox status, probably mediated by jasmonic acid and ethylene, play an important role in the primary root meristem exhaustion process triggered by Pi-starvation. PMID:21368582

Selective ablation of Ppp1cc gene in testicular germ cells causes oligo-teratozoospermia and infertility in mice.

PubMed

Sinha, Nilam; Puri, Pawan; Nairn, Angus C; Vijayaraghavan, Srinivasan

2013-11-01

The four isoforms of serine/threonine phosphoprotein phosphatase 1 (PP1), derived from three genes, are among the most conserved proteins known. The Ppp1cc gene encodes two alternatively spliced variants, PP1 gamma1 (PPP1CC1) and PP1 gamma2 (PPP1CC2). Global deletion of the Ppp1cc gene, which causes loss of both isoforms, results in male infertility due to impaired spermatogenesis. This phenotype was assumed to be due to the loss of PPP1CC2, which is abundant in testis. While PPP1CC2 is predominant, other PP1 isoforms are also expressed in testis. Given the significant homology between the four PP1 isoforms, the lack of compensation by the other PP1 isoforms for loss of one, only in testis, is surprising. Here we document, for the first time, expression patterns of the PP1 isoforms in postnatal developing and adult mouse testis. The timing and sites of testis expression of PPP1CC1 and PPP1CC2 in testis are nonoverlapping. PPP1CC2 is the only one of the four PP1 isoforms not detected in sertoli cells and spermatogonia. Conversely, PPP1CC2 may be the only PP1 isoform expressed in postmeiotic germ cells. Deletion of the Ppp1cc gene in germ cells at the differentiated spermatogonia stage of development and beyond in Stra8 promoter-driven Cre transgenic mice results in oligo-terato-asthenozoospermia and male infertility, thus phenocopying global Ppp1cc null (-/-) mice. Taken together, these results confirm that spermatogenic defects observed in the global Ppp1cc knockout mice and in mice expressing low levels of PPP1CC2 in testis are due to compromised functions of PPP1CC2 in meiotic and postmeiotic germ cells.

Identification and characterization of the grape WRKY family.

PubMed

Zhang, Ying; Feng, Jian Can

2014-01-01

WRKY transcription factors have functions in plant growth and development and in response to biotic and abiotic stresses. Many studies have focused on functional identification of WRKY transcription factors, but little is known about the molecular phylogeny or global expression patterns of the complete WRKY family. In this study, we identified 80 WRKY proteins encoded in the grape genome. Based on the structural features of these proteins, the grape WRKY genes were classified into three groups (groups 1-3). Analysis of WRKY genes expression profiles indicated that 28 WRKY genes were differentially expressed in response to biotic stress caused by grape whiterot and/or salicylic acid (SA). In that 16 WRKY genes upregulated both by whiterot pathogenic bacteria and SA. The results indicated that 16 WRKY proteins participated in SA-dependent defense signal pathway. This study provides a basis for cloning genes with specific functions from grape.

Gene expression changes in honey bees induced by sublethal imidacloprid exposure during the larval stage.

PubMed

Wu, Ming-Cheng; Chang, Yu-Wen; Lu, Kuang-Hui; Yang, En-Cheng

2017-09-01

Honey bee larvae exposed to sublethal doses of imidacloprid show behavioural abnormalities as adult insects. Previous studies have demonstrated that this phenomenon originates from abnormal neural development in response to imidacloprid exposure. Here, we further investigated the global gene expression changes in the heads of newly emerged adults and observed that 578 genes showed more than 2-fold changes in gene expression after imidacloprid exposure. This information might aid in understanding the effects of pesticides on the health of pollinators. For example, the genes encoding major royal jelly proteins (MRJPs), a group of multifunctional proteins with significant roles in the sustainable development of bee colonies, were strongly downregulated. These downregulation patterns were further confirmed through analyses using quantitative reverse transcription-polymerase chain reaction on the heads of 6-day-old nurse bees. To our knowledge, this study is the first to demonstrate that sublethal doses of imidacloprid affect mrjp expression and likely weaken bee colonies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fractal Clustering and Knowledge-driven Validation Assessment for Gene Expression Profiling.

PubMed

Wang, Lu-Yong; Balasubramanian, Ammaiappan; Chakraborty, Amit; Comaniciu, Dorin

2005-01-01

DNA microarray experiments generate a substantial amount of information about the global gene expression. Gene expression profiles can be represented as points in multi-dimensional space. It is essential to identify relevant groups of genes in biomedical research. Clustering is helpful in pattern recognition in gene expression profiles. A number of clustering techniques have been introduced. However, these traditional methods mainly utilize shape-based assumption or some distance metric to cluster the points in multi-dimension linear Euclidean space. Their results shows poor consistence with the functional annotation of genes in previous validation study. From a novel different perspective, we propose fractal clustering method to cluster genes using intrinsic (fractal) dimension from modern geometry. This method clusters points in such a way that points in the same clusters are more self-affine among themselves than to the points in other clusters. We assess this method using annotation-based validation assessment for gene clusters. It shows that this method is superior in identifying functional related gene groups than other traditional methods.

Non-canonical TAF complexes regulate active promoters in human embryonic stem cells.

PubMed

Maston, Glenn A; Zhu, Lihua Julie; Chamberlain, Lynn; Lin, Ling; Fang, Minggang; Green, Michael R

2012-11-13

The general transcription factor TFIID comprises the TATA-box-binding protein (TBP) and approximately 14 TBP-associated factors (TAFs). Here we find, unexpectedly, that undifferentiated human embryonic stem cells (hESCs) contain only six TAFs (TAFs 2, 3, 5, 6, 7 and 11), whereas following differentiation all TAFs are expressed. Directed and global chromatin immunoprecipitation analyses reveal an unprecedented promoter occupancy pattern: most active genes are bound by only TAFs 3 and 5 along with TBP, whereas the remaining active genes are bound by TBP and all six hESC TAFs. Consistent with these results, hESCs contain a previously undescribed complex comprising TAFs 2, 6, 7, 11 and TBP. Altering the composition of hESC TAFs, either by depleting TAFs that are present or ectopically expressing TAFs that are absent, results in misregulated expression of pluripotency genes and induction of differentiation. Thus, the selective expression and use of TAFs underlies the ability of hESCs to self-renew.DOI:http://dx.doi.org/10.7554/eLife.00068.001.

Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis

NASA Astrophysics Data System (ADS)

Kaminski, Naftali; Allard, John D.; Pittet, Jean F.; Zuo, Fengrong; Griffiths, Mark J. D.; Morris, David; Huang, Xiaozhu; Sheppard, Dean; Heller, Renu A.

2000-02-01

The molecular mechanisms of pulmonary fibrosis are poorly understood. We have used oligonucleotide arrays to analyze the gene expression programs that underlie pulmonary fibrosis in response to bleomycin, a drug that causes lung inflammation and fibrosis, in two strains of susceptible mice (129 and C57BL/6). We then compared the gene expression patterns in these mice with 129 mice carrying a null mutation in the epithelial-restricted integrin 6 subunit (6/-), which develop inflammation but are protected from pulmonary fibrosis. Cluster analysis identified two distinct groups of genes involved in the inflammatory and fibrotic responses. Analysis of gene expression at multiple time points after bleomycin administration revealed sequential induction of subsets of genes that characterize each response. The availability of this comprehensive data set should accelerate the development of more effective strategies for intervention at the various stages in the development of fibrotic diseases of the lungs and other organs.

Anteroposterior Patterning of Gene Expression in the Human Infant Sclera: Chondrogenic Potential and Wnt Signaling.

PubMed

Seko, Yuko; Azuma, Noriyuki; Yokoi, Tadashi; Kami, Daisuke; Ishii, Ryuga; Nishina, Sachiko; Toyoda, Masashi; Shimokawa, Hitoyata; Umezawa, Akihiro

2017-01-01

Purpose/Aim: We sought to identify the anteroposterior spatial gene expression hierarchy in the human sclera to develop a hypothesis for axial elongation and deformity of the eyeball. We analyzed the global gene expression of human scleral cells derived from distinct parts of the human infant sclera obtained from surgically enucleated eyes with retinoblastoma, using Affymetrix GeneChip oligonucleotide arrays, and compared, in particular, gene expression levels between the anterior and posterior parts of the sclera. The ages of three donors were 10M, 4M, and 1Y9M. K-means clustering analysis of gene expression revealed that expression levels of cartilage-associated genes such as COLXIA and ACAN increased from the anterior to the posterior part of the sclera. Microarray analyses and RT-PCR data showed that the expression levels of MGP, COLXIA, BMP4, and RARB were significantly higher in the posterior than in the anterior sclera of two independent infant eyes. Conversely, expression levels of WNT2, DKK2, GREM1, and HOXB2 were significantly higher in the anterior sclera. Among several Wnt-family genes examined, WNT2B was found to be expressed at a significantly higher level in the posterior sclera, and the reverse order was observed for WNT2. The results of luciferase reporter assays suggested that a GSK-3β inhibitor stimulated Wnt/β-catenin signaling particularly strongly in the posterior sclera. The expression pattern of RARB, a myopia-related gene, was similar in three independent eyes. Chondrogenic potential was higher and Wnt/β-catenin signaling was more potently activated by a GSK-3β inhibitor in the posterior than in the anterior part of the human infant sclera. Although the differences in the gene expression profiles between the anterior and posterior sclera might be involved only in normal growth processes, this anteroposterior hierarchy in the sclera might contribute to disorders involving abnormal elongation and deformity of the eyeball, including myopia.

Lipidomic fatty acid profile and global gene expression pattern in mammary gland of rats that were exposed to lard-based high fat diet during fetal and lactation periods associated to breast cancer risk in adulthood.

PubMed

Andrade, Fábia de Oliveira; de Assis, Sonia; Jin, Lu; Fontelles, Camile Castilho; Barbisan, Luís Fernando; Purgatto, Eduardo; Hilakivi-Clarke, Leena; Ong, Thomas Prates

2015-09-05

The persistent effects of animal fat consumption during pregnancy and nursing on the programming of breast cancer risk among female offspring were studied here. We have previously found that female offspring of rat dams that consumed a lard-based high-fat (HF) diet (60% fat-derived energy) during pregnancy, or during pregnancy and lactation, were at a reduced risk of developing mammary cancer. To better understand the unexpected protective effects of early life lard exposure, we have applied lipidomics and nutrigenomics approaches to investigate the fatty acid profile and global gene expression patterns in the mammary tissue of the female offspring. Consumption of this HF diet during gestation had few effects on the mammary tissue fatty acids profile of young adult offspring, while exposure from gestation throughout nursing promoted significant alterations in the fatty acids profile. Major differences were related to decreases in saturated fatty acids (SFA) and increases in omega-6 polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs) and conjugated linolenic acid (CLA) concentrations. In addition several differences in gene expression patterns by microarray analysis between the control and in utero or in utero and during lactation HF exposed offspring were identified. Differential dependency network (DDN) analysis indicated that many of the genes exhibited unique connections to other genes only in the HF offspring. These unique connections included Hrh1-Ythdf1 and Repin1-Elavl2 in the in utero HF offspring, and Rnf213-Htr3b and Klf5-Chrna4 in the in utero and lactation HF offspring, compared with the control offspring. We conclude that an exposure to a lard-based HF diet during early life changes the fatty acid profile and transcriptional network in mammary gland in young adult rats, and these changes appear to be consistent with reduced mammary cancer risk observed in our previous study. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Aberrant transcriptional networks in step-wise neurogenesis of paroxysmal kinesigenic dyskinesia-induced pluripotent stem cells.

PubMed

Li, Chun; Ma, Yu; Zhang, Kunshan; Gu, Junjie; Tang, Fan; Chen, Shengdi; Cao, Li; Li, Siguang; Jin, Ying

2016-08-16

Paroxysmal kinesigenic dyskinesia (PKD) is an episodic movement disorder with autosomal-dominant inheritance and marked variability in clinical manifestations.Proline-rich transmembrane protein 2 (PRRT2) has been identified as a causative gene of PKD, but the molecular mechanism underlying the pathogenesis of PKD still remains a mystery. The phenotypes and transcriptional patterns of the PKD disease need further clarification. Here, we report the generation and neural differentiation of iPSC lines from two familial PKD patients with c.487C>T (p. Gln163X) and c.573dupT (p. Gly192Trpfs*8) PRRT2 mutations, respectively. Notably, an extremely lower efficiency in neural conversion from PKD-iPSCs than control-iPSCs is observed by a step-wise neural differentiation method of dual inhibition of SMAD signaling. Moreover, we show the high expression level of PRRT2 throughout the human brain and the expression pattern of PRRT2 in other human tissues for the first time. To gain molecular insight into the development of the disease, we conduct global gene expression profiling of PKD cells at four different stages of neural induction and identify altered gene expression patterns, which peculiarly reflect dysregulated neural transcriptome signatures and a differentiation tendency to mesodermal development, in comparison to control-iPSCs. Additionally, functional and signaling pathway analyses indicate significantly different cell fate determination between PKD-iPSCs and control-iPSCs. Together, the establishment of PKD-specific in vitro models and the illustration of transcriptome features in PKD cells would certainly help us with better understanding of the defects in neural conversion as well as further investigations in the pathogenesis of the PKD disease.

PINK1 is required for timely cell-type specific mitochondrial clearance during Drosophila midgut metamorphosis.

PubMed

Liu, Yan; Lin, Jingjing; Zhang, Minjie; Chen, Kai; Yang, Shengxi; Wang, Qun; Yang, Hongqin; Xie, Shusen; Zhou, Yongjian; Zhang, Xi; Chen, Fei; Yang, Yufeng

2016-11-15

Mitophagy is the selective degradation of mitochondria by autophagy, which is an important mitochondrial quality and quantity control process. During Drosophila metamorphosis, the degradation of midgut involves a large change in length and organization, which is mediated by autophagy. Here we noticed a cell-type specific mitochondrial clearance process that occurs in enterocytes (ECs), while most mitochondria remain in intestinal stem cells (ISCs) during metamorphosis. Although PINK1/PARKIN represent the canonical pathway for the elimination of impaired mitochondria in varied pathological conditions, their roles in developmental processes or normal physiological conditions have been less studied. To examine the potential contribution of PINK1 in developmental processes, we monitored the dynamic expression pattern of PINK1 in the midgut development by taking advantage of a newly CRISPR/Cas9 generated knock-in fly strain expressing PINK1-mCherry fusion protein that presumably recapitulates the endogenous expression pattern of PINK1. We disclosed a spatiotemporal correlation between the expression pattern of PINK1 and the mitochondrial clearance or persistence in ECs or ISCs respectively. By mosaic genetic analysis, we then demonstrated that PINK1 and PARKIN function epistatically to mediate the specific timely removal of mitochondria, and are involved in global autophagy in ECs during Drosophila midgut metamorphosis, with kinase-dead PINK1 exerting dominant negative effects. Taken together, our studies concluded that the PINK1/PARKIN is crucial for timely cell-type specific mitophagy under physiological conditions and demonstrated again that Drosophila midgut metamorphosis might serve as an elegant in vivo model to study autophagy. Copyright © 2016 Elsevier Inc. All rights reserved.

Precipitation, temperature, and teleconnection signals across the combined North American, Monsoon Asia, and Old World Drought Atlases

NASA Astrophysics Data System (ADS)

Smerdon, J. E.; Baek, S. H.; Coats, S.; Williams, P.; Cook, B.; Cook, E. R.; Seager, R.

2017-12-01

The tree-ring-based North American Drought Atlas (NADA), Monsoon Asia Drought Atlas (MADA), and Old World Drought Atlas (OWDA) collectively yield a near-hemispheric gridded reconstruction of hydroclimate variability over the last millennium. To test the robustness of the large-scale representation of hydroclimate variability across the drought atlases, the joint expression of seasonal climate variability and teleconnections in the NADA, MADA, and OWDA are compared against two global, observation-based PDSI products. Predominantly positive (negative) correlations are determined between seasonal precipitation (surface air temperature) and collocated tree-ring-based PDSI, with average Pearson's correlation coefficients increasing in magnitude from boreal winter to summer. For precipitation, these correlations tend to be stronger in the boreal winter and summer when calculated for the observed PDSI record, while remaining similar for temperature. Notwithstanding these differences, the drought atlases robustly express teleconnection patterns associated with the El Niño-Southern Oscillation (ENSO), North Atlantic Oscillation (NAO), Pacific Decadal Oscillation (PDO), and Atlantic Multidecadal Oscillation (AMO). These expressions exist in the drought atlas estimates of boreal summer PDSI despite the fact that these modes of climate variability are dominant in boreal winter, with the exception of the Atlantic Multidecadal Oscillation. ENSO and NAO teleconnection patterns in the drought atlases are particularly consistent with their well-known dominant expressions in boreal winter and over the OWDA domain, respectively. Collectively, our findings confirm that the joint Northern Hemisphere drought atlases robustly reflect large-scale patterns of hydroclimate variability on seasonal to multidecadal timescales over the 20th century and are likely to provide similarly robust estimates of hydroclimate variability prior to the existence of widespread instrumental data.

Local sources of retinoic acid coincide with retinoid-mediated transgene activity during embryonic development.

PubMed Central

Colbert, M C; Linney, E; LaMantia, A S

1993-01-01

We have assessed whether retinoic acid (RA) comes from local sources or is available widely to activate gene expression in embryos. We used an RA-responsive indicator cell line, L-C2A5, to localize RA sources. In these cells, an RA-sensitive promoter/lacZ reporter construct used previously by us to produce indicator transgenic mice is induced globally by RA in medium or locally by RA released at physiological concentrations (1 nM) from AG-1X2 resin beads. Furthermore, the cells are differentially responsive to the 9-cis and all-trans isomers of RA at low concentrations. Indicator transgenic mice with the same promoter/reporter construct were used to identify regions of RA-mediated gene activation. There are distinct domains of lacZ expression in the cervical and lumbar spinal cords of embryonic indicator mice. This pattern might reflect localized RA sources or restricted spatial and temporal expression of RA receptors, binding proteins, or other factors. To resolve this issue we compared the pattern of transgene activation in indicator cell monolayers cocultured with normal embryonic spinal cords with that in transgenic spinal cords. The explants induced reporter gene expression in L-C2A5 monolayers in a pattern identical to that in transgenic mice: alar regions of the cervical and lumbar cord were positive whereas those in the thoracic and sacral regions were not. We conclude that restricted sources of RA in the developing spinal cord mediate the local activation of RA-inducible genes. Thus, region-specific gene activation in embryos can be mediated by precisely localized sources of inductive molecules like RA. Images Fig. 1 Fig. 2 Fig. 3 PMID:8341670

Gene Expression, DNA Methylation and Prognostic Significance of DNA Repair Genes in Human Bladder Cancer.

PubMed

Wojtczyk-Miaskowska, Anita; Presler, Malgorzata; Michajlowski, Jerzy; Matuszewski, Marcin; Schlichtholz, Beata

2017-01-01

This study investigated the gene expression and DNA methylation of selected DNA repair genes (MBD4, TDG, MLH1, MLH3) and DNMT1 in human bladder cancer in the context of pathophysiological and prognostic significance. To determine the relationship between the gene expression pattern, global methylation and promoter methylation status, we performed real-time PCR to quantify the mRNA of selected genes in 50 samples of bladder cancer and adjacent non-cancerous tissue. The methylation status was analyzed by methylation-specific polymerase chain reaction (MSP) or digestion of genomic DNA with a methylation-sensitive restriction enzyme and PCR with gene-specific primers (MSRE-PCR). The global DNA methylation level was measured using the antibody-based 5-mC detection method. The relative levels of mRNA for MBD4, MLH3, and MLH1 were decreased in 28% (14/50), 34% (17/50) and 36% (18/50) of tumor samples, respectively. The MBD4 mRNA expression was decreased in 46% of non-muscle invasive tumors (Ta/T1) compared with 11% found in muscle invasive tumors (T2-T4) (P<0.003). Analysis of mRNA expression for TDG did not show any significant differences between Ta/T1 and T2-T4 tumors. The frequency of increased DNMT1 mRNA expression was higher in T2-T4 (52%) comparing to Ta/T1 (16%). The overall methylation rates in tumor tissue were 18% for MBD4, 25% for MLH1 and there was no evidence of MLH3 promoter methylation. High grade tumors had significantly lower levels of global DNA methylation (P=0.04). There was a significant association between shorter survival and increased expression of DNMT1 mRNA (P=0.002), decreased expression of MLH1 mRNA (P=0.032) and the presence of MLH1 promoter methylation (P=0.006). This study highlights the importance of DNA repair pathways and provides the first evidence of the role of MBD4 and MLH3 in bladder cancer. In addition, our findings suggest that DNMT1 mRNA and MLH1 mRNA expression, as well as the status of MLH1 promoter methylation, are attractive prognostic markers in this pathology. © 2017 The Author(s). Published by S. Karger AG, Basel.

A global RNA-seq-driven analysis of CHO host and production cell lines reveals distinct differential expression patterns of genes contributing to recombinant antibody glycosylation.

PubMed

Könitzer, Jennifer D; Müller, Markus M; Leparc, Germán; Pauers, Martin; Bechmann, Jan; Schulz, Patrick; Schaub, Jochen; Enenkel, Barbara; Hildebrandt, Tobias; Hampel, Martin; Tolstrup, Anne B

2015-09-01

Boehringer Ingelheim uses two CHO-DG44 lines for manufacturing biotherapeutics, BI-HEX-1 and BI-HEX-2, which produce distinct cell type-specific antibody glycosylation patterns. A recently established CHO-K1 descended host, BI-HEX-K1, generates antibodies with glycosylation profiles differing from CHO-DG44. Manufacturing process development is significantly influenced by these unique profiles. To investigate the underlying glycosylation related gene expression, we leveraged our CHO host and production cell RNA-seqtranscriptomics and product quality database together with the CHO-K1 genome. We observed that each BI-HEX host and antibody producing cell line has a unique gene expression fingerprint. CHO-DG44 cells only transcribe Fut10, Gfpt2 and ST8Sia6 when expressing antibodies. BI-HEX-K1 cells express ST8Sia6 at host cell level. We detected a link between BI-HEX-1/BI-HEX-2 antibody galactosylation and mannosylation and the gene expression of the B4galt gene family and genes controlling mannose processing. Furthermore, we found major differences between the CHO-DG44 and CHO-K1 lineages in the expression of sialyl transferases and enzymes synthesizing sialic acid precursors, providing a rationale for the lack of immunogenic NeuGc/NGNA synthesis in CHO. Our study highlights the value of systems biotechnology to understand glycoprotein synthesis and product glycoprofiles. Such data improve future production clone selection and process development strategies for better steering of biotherapeutic product quality. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of cloning by chromatin transfer on placental gene expression at Day 45 of pregnancy in cattle.

PubMed

Mesquita, Fernando S; Machado, Sergio A; Drnevich, Jenny; Borowicz, Pawel; Wang, Zhongde; Nowak, Romana A

2013-01-30

Poor success rates in somatic cell cloning are often attributed to abnormal early embryonic development as well as late abnormal fetal growth and placental development. Although promising results have been reported following chromatin transfer (CT), a novel cloning method that includes the remodeling of the donor nuclei in vitro prior to their transfer into enucleated oocytes, animals cloned by CT show placental abnormalities similar to those observed following conventional nuclear transfer. We hypothesized that the placental gene expression pattern from cloned fetuses was ontologically related to the frequently observed placental phenotype. The aim of the present study was to compare global gene expression by microarray analysis of Day 44-47 cattle placentas derived from CT cloned fetuses with those derived from in vitro fertilization (i.e. control), and confirm the altered mRNA and protein expression of selected molecules by qRT-PCR and immunohistochemistry, respectively. The differentially expressed genes identified in the present study are known to be involved in a range of activities associated with cell adhesion, cell cycle control, intracellular transport and proteolysis. Specifically, an imprinted gene, involved with cell proliferation and placentomegaly in humans (CDKN1C) and a peptidase that serves as a marker for non-invasive trophoblast cells in human placentas (DPP4), had mRNA and protein altered in CT placentas. It was concluded that the altered pattern of gene expression observed in CT samples may contribute to the abnormal placental development phenotypes commonly identified in cloned offspring, and that expression of imprinted as well as trophoblast invasiveness-related genes is altered in cattle cloned by CT. Copyright © 2012 Elsevier B.V. All rights reserved.

Expression of HSPs: an adaptive mechanism during long-term heat stress in goats ( Capra hircus)

NASA Astrophysics Data System (ADS)

Dangi, Satyaveer Singh; Gupta, Mahesh; Dangi, Saroj K.; Chouhan, Vikrant Singh; Maurya, V. P.; Kumar, Puneet; Singh, Gyanendra; Sarkar, Mihir

2015-08-01

Menacing global rise in surface temperature compelled more focus of research over understanding heat stress response mechanism of animals and mitigation of heat stress. Twenty-four goats divided into four groups ( n = 6) such as NHS (non-heat-stressed), HS (heat-stressed), HS + VC (heat-stressed administered with vitamin C), and HS + VE + Se (heat-stressed administered with vitamin E and selenium). Except NHS group, other groups were exposed to repeated heat stress (42 °C) for 6 h on 16 consecutive days. Blood samples were collected at the end of heat exposure on days 1, 6, 11, and 16. When groups compared between days, expression of all heat shock proteins (HSPs) showed a similar pattern as first peak on day 1, reached to basal level on the sixth day, and followed by second peak on day 16. The relative messenger RNA (mRNA) and protein expression of HSP 60, HSP70, and HSP90 was observed highest ( P < 0.05) in HS group, followed by antioxidant-administered group on days 1 and 16, which signifies that antioxidants have dampening effect on HSP expression. HSP105/110 expression was highest ( P < 0.05) on day 16. We conclude that HSP expression pattern is at least two-peak phenomenon, i.e., primary window of HSP protection on the first day followed by second window of protection on day 16. HSP60, HSP70, and HSP90 play an important role during the initial phase of heat stress acclimation whereas HSP105/110 joins this cascade at later phase. Antioxidants may possibly attenuate the HSP expression by reducing the oxidative stress.

Species pool, human population, and global versus regional invasion patterns

Treesearch

Qinfeng Guo; Basil V. Iannone III; Gabriela C. Nunez-Mir; Kevin M. Potter; Christopher M. Oswalt; Songlin Fei

2017-01-01

Context Biological invasions are among the greatest global and regional threats to biomes in the Anthropocene. Islands, in particular, have been perceived to have higher vulnerability to invasions. Because of the dynamic nature of ongoing invasions, distinguishing regional patterns from global patterns and their underlying determinants remains a challenge. Objectives...

Narcolepsy patients' blood-based miRNA expression profiling: miRNA expression differences with Pandemrix vaccination.

PubMed

Mosakhani, N; Sarhadi, V; Panula, P; Partinen, M; Knuutila, S

2017-11-01

Narcolepsy is a neurological sleep disorder characterized by excessive daytime sleepiness and nighttime sleep disturbance. Among children and adolescents vaccinated with Pandemrix vaccine in Finland and Sweden, the number of narcolepsy cases increased. Our aim was to identify miRNAs involved in narcolepsy and their association with Pandemrix vaccination. We performed global miRNA proofing by miRNA microarrays followed by RT-PCR verification on 20 narcolepsy patients (Pandemrix-associated and Pandemrix-non-associated) and 17 controls (vaccinated and non-vaccinated). Between all narcolepsy patients and controls, 11 miRNAs were differentially expressed; 17 miRNAs showed significantly differential expression between Pandemrix-non-associated narcolepsy patients and non-vaccinated healthy controls. MiR-188-5p and miR-4499 were over-expressed in narcolepsy patients vs healthy controls. Two miRNAs, miR-1470 and miR-4455, were under-expressed in Pandemrix-associated narcolepsy patients vs Pandemrix-non-associated narcolepsy patients. We identified miRNA expression patterns in narcolepsy patients that linked them to mRNA targets known to be involved in brain-related pathways or brain disorders. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Culinary culture and globalization: an analysis of British and German Michelin-starred restaurants.

PubMed

Lane, Christel

2011-12-01

The high-end restaurant segment in Britain and Germany has long been shaped by the cultural hegemony of French haute cuisine, perpetuated by multiple processes, including the influence of the Michelin or Red Guide. Traditionally, this hegemony has been expressed in the prevalence of French expatriate chefs, culinary techniques and style and even restaurant culture. This paper investigates whether processes of globalization have weakened or even undermined this French cultural dominance in fine-dining restaurants and their culinary culture. To this end, the study identifies the various forms taken by globalization processes in this industry segment and then assesses their impact on the dominance of the French paradigm of culinary culture. The investigation focuses on British and German Michelin-starred restaurants, underlining both commonalities and divergences in the process of interaction between French, global and local influences. The study employs a qualitative method, using a number of case studies to discern cross-industry patterns. All chefs with two or three stars in the two countries, i.e. 45 chefs, were selected for the analysis of their cuisine. © London School of Economics and Political Science 2011.

The BET protein FSH functionally interacts with ASH1 to orchestrate global gene activity in Drosophila

PubMed Central

2013-01-01

Background The question of how cells re-establish gene expression states after cell division is still poorly understood. Genetic and molecular analyses have indicated that Trithorax group (TrxG) proteins are critical for the long-term maintenance of active gene expression states in many organisms. A generally accepted model suggests that TrxG proteins contribute to maintenance of transcription by protecting genes from inappropriate Polycomb group (PcG)-mediated silencing, instead of directly promoting transcription. Results and discussion Here we report a physical and functional interaction in Drosophila between two members of the TrxG, the histone methyltransferase ASH1 and the bromodomain and extraterminal family protein FSH. We investigated this interface at the genome level, uncovering a widespread co-localization of both proteins at promoters and PcG-bound intergenic elements. Our integrative analysis of chromatin maps and gene expression profiles revealed that the observed ASH1-FSH binding pattern at promoters is a hallmark of active genes. Inhibition of FSH-binding to chromatin resulted in global down-regulation of transcription. In addition, we found that genes displaying marks of robust PcG-mediated repression also have ASH1 and FSH bound to their promoters. Conclusions Our data strongly favor a global coactivator function of ASH1 and FSH during transcription, as opposed to the notion that TrxG proteins impede inappropriate PcG-mediated silencing, but are dispensable elsewhere. Instead, our results suggest that PcG repression needs to overcome the transcription-promoting function of ASH1 and FSH in order to silence genes. PMID:23442797

Epidermal Phytochrome B Inhibits Hypocotyl Negative Gravitropism Non-Cell-Autonomously.

PubMed

Kim, Jaewook; Song, Kijong; Park, Eunae; Kim, Keunhwa; Bae, Gabyong; Choi, Giltsu

2016-11-01

Seedling hypocotyls display negative gravitropism in the dark but agravitropism in the light. The Arabidopsis thaliana pif quadruple mutant (pifQ), which lacks four PHYTOCHROME-INTERACTING FACTORS (PIFs), is agravitropic in the dark. Endodermis-specific expression of PIF1 rescues gravitropism in pifQ mutant seedlings. Since phytochromes induce light responses by inhibiting PIFs and the COP1-SPA ubiquitin E3 ligase complex in the nucleus, we asked whether phyB can cell autonomously inhibit hypocotyl negative gravitropism in the endodermis. We found that while epidermis-specific expression of PHYB rescues hypocotyl negative gravitropism and all other phyB mutant phenotypes, endodermis-specific expression of PHYB does not. Epidermal phyB induces the phosphorylation and degradation of endodermal PIFs in response to red light. This induces a global gene expression pattern similar to that induced by red light treatment of seedlings expressing PHYB under the control of its own endogenous promoter. Our results imply that epidermal phyB generates an unidentified mobile signal that travels to the endodermis where it promotes PIF degradation and inhibits hypocotyl negative gravitropism. © 2016 American Society of Plant Biologists. All rights reserved.

Epidermal Phytochrome B Inhibits Hypocotyl Negative Gravitropism Non-Cell-Autonomously

PubMed Central

Kim, Jaewook; Song, Kijong; Park, Eunae; Kim, Keunhwa; Choi, Giltsu

2016-01-01

Seedling hypocotyls display negative gravitropism in the dark but agravitropism in the light. The Arabidopsis thaliana pif quadruple mutant (pifQ), which lacks four PHYTOCHROME-INTERACTING FACTORS (PIFs), is agravitropic in the dark. Endodermis-specific expression of PIF1 rescues gravitropism in pifQ mutant seedlings. Since phytochromes induce light responses by inhibiting PIFs and the COP1-SPA ubiquitin E3 ligase complex in the nucleus, we asked whether phyB can cell autonomously inhibit hypocotyl negative gravitropism in the endodermis. We found that while epidermis-specific expression of PHYB rescues hypocotyl negative gravitropism and all other phyB mutant phenotypes, endodermis-specific expression of PHYB does not. Epidermal phyB induces the phosphorylation and degradation of endodermal PIFs in response to red light. This induces a global gene expression pattern similar to that induced by red light treatment of seedlings expressing PHYB under the control of its own endogenous promoter. Our results imply that epidermal phyB generates an unidentified mobile signal that travels to the endodermis where it promotes PIF degradation and inhibits hypocotyl negative gravitropism. PMID:27758895

The low noise limit in gene expression

DOE PAGES

Dar, Roy D.; Weinberger, Leor S.; Cox, Chris D.; ...

2015-10-21

Protein noise measurements are increasingly used to elucidate biophysical parameters. Unfortunately noise analyses are often at odds with directly measured parameters. Here we show that these inconsistencies arise from two problematic analytical choices: (i) the assumption that protein translation rate is invariant for different proteins of different abundances, which has inadvertently led to (ii) the assumption that a large constitutive extrinsic noise sets the low noise limit in gene expression. While growing evidence suggests that transcriptional bursting may set the low noise limit, variability in translational bursting has been largely ignored. We show that genome-wide systematic variation in translational efficiencymore » can-and in the case of E. coli does-control the low noise limit in gene expression. Therefore constitutive extrinsic noise is small and only plays a role in the absence of a systematic variation in translational efficiency. Lastly, these results show the existence of two distinct expression noise patterns: (1) a global noise floor uniformly imposed on all genes by expression bursting; and (2) high noise distributed to only a select group of genes.« less

Temperature, energy metabolism, and adaptive divergence in two oyster subspecies.

PubMed

Li, Ao; Li, Li; Song, Kai; Wang, Wei; Zhang, Guofan

2017-08-01

Comparisons of related species that have diverse spatial distributions provide an efficient way to investigate adaptive evolution in face of increasing global warming. The oyster subjected to high environmental selections is a model species as sessile marine invertebrate. This study aimed to detect the adaptive divergence of energy metabolism in two oyster subspecies from the genus Crassostrea - C. gigas gigas and C. gigas angulata -which are broadly distributed along the northern and southern coasts of China, respectively. We examined the effects of acute thermal stress on energy metabolism in two oyster subspecies after being common gardened for one generation in identical conditions. Thermal responses were assessed by incorporating physiological, molecular, and genomic approaches. Southern oysters exhibited higher fluctuations in metabolic rate, activities of key energetic enzymes, and levels of thermally induced gene expression than northern oysters. For genes involved in energy metabolism, the former displayed higher basal levels of gene expression and a more pronounced downregulation of thermally induced expression, while the later exhibited lower basal levels and a less pronounced downregulation of gene expression. Contrary expression pattern was observed in oxidative stress gene. Besides, energy metabolic tradeoffs were detected in both subspecies. Furthermore, the genetic divergence of a nonsynonymous SNP ( SOD-132 ) and five synonymous SNPs in other genes was identified and validated in these two subspecies, which possibly affects downstream functions and explains the aforementioned phenotypic variations. Our study demonstrates that differentiations in energy metabolism underlie the plasticity of adaptive divergence in two oyster subspecies and suggest C. gigas angulata with moderate phenotypic plasticity has higher adaptive potential to cope with exacerbated global warming.

Global gene expression analysis of the heat shock response in the phytopathogen Xylella fastidiosa.

PubMed

Koide, Tie; Vêncio, Ricardo Z N; Gomes, Suely L

2006-08-01

Xylella fastidiosa is a phytopathogenic bacterium that is responsible for diseases in many economically important crops. Although different strains have been studied, little is known about X. fastidiosa stress responses. One of the better characterized stress responses in bacteria is the heat shock response, which induces the expression of specific genes to prevent protein misfolding and aggregation and to promote degradation of the irreversibly denatured polypeptides. To investigate X. fastidiosa genes involved in the heat shock response, we performed a whole-genome microarray analysis in a time course experiment. Globally, 261 genes were induced (9.7%) and 222 genes were repressed (8.3%). The expression profiles of the differentially expressed genes were grouped, and their expression patterns were validated by quantitative reverse transcription-PCR experiments. We determined the transcription start sites of six heat shock-inducible genes and analyzed their promoter regions, which allowed us to propose a putative consensus for sigma(32) promoters in Xylella and to suggest additional genes as putative members of this regulon. Besides the induction of classical heat shock protein genes, we observed the up-regulation of virulence-associated genes such as vapD and of genes for hemagglutinins, hemolysin, and xylan-degrading enzymes, which may indicate the importance of heat stress to bacterial pathogenesis. In addition, we observed the repression of genes related to fimbriae, aerobic respiration, and protein biosynthesis and the induction of genes related to the extracytoplasmic stress response and some phage-related genes, revealing the complex network of genes that work together in response to heat shock.

Architectural patterns of p16 immunohistochemical expression associated with cancer immunity and prognosis of head and neck squamous cell carcinoma.

PubMed

Ryu, Hyang Joo; Kim, Eun Kyung; Heo, Su Jin; Cho, Byoung Chul; Kim, Hye Ryun; Yoon, Sun Och

2017-11-01

We evaluated the expression patterns of p16, which is used as a surrogate marker of HPV infection in head and neck squamous cell carcinoma (HNSCC), in regard to their biological and prognostic implications. p16 expression patterns and infiltrated immune cells were analyzed through immunohistochemistry of p16, CD3, CD8, PD-1, FOXP3, and CD163 on surgically resected HNSCCs (n = 393). Patterns of p16 immunoexpression were defined as STRONG (strong, diffuse expression in cytoplasm, and nucleus in >70% of tumor cells), MARGINAL (expression restricted to tumor margins), MOSAIC (ragged, discontinued expression), NUCLEAR (expression in nuclei only), and ABSENT (no expression). The STRONG pattern was more frequent in the oropharynx, and the MARGINAL pattern was noted only in the oral cavity. MOSAIC and NUCLEAR patterns were noted at variable sites. No two patterns of p16 expression showed the same immune cell composition of CD3+ T cells, CD8+ cytotoxic T cells, PD-1+ T cells, FOXP3+ regulatory T cells, and CD163+ macrophages. In overall and disease-free survival analyses, the STRONG pattern showed the most favorable prognosis, while the NUCLEAR pattern had the worst prognosis. HNSCC anatomical sites, tumor-related immune cell components, and patient outcomes were associated with p16 expression patterns. Each architectural pattern of p16 expression may be related to different biological and prognostic phenotypes. © 2017 APMIS. Published by John Wiley & Sons Ltd.

The Role of Dietary Extra Virgin Olive Oil and Corn Oil on the Alteration of Epigenetic Patterns in the Rat DMBA-Induced Breast Cancer Model.

PubMed

Rodríguez-Miguel, Cristina; Moral, Raquel; Escrich, Raquel; Vela, Elena; Solanas, Montserrat; Escrich, Eduard

2015-01-01

Disruption of epigenetic patterns is a major change occurring in all types of cancers. Such alterations are characterized by global DNA hypomethylation, gene-promoter hypermethylation and aberrant histone modifications, and may be modified by environment. Nutritional factors, and especially dietary lipids, have a role in the etiology of breast cancer. Thus, we aimed to analyze the influence of different high fat diets on DNA methylation and histone modifications in the rat dimethylbenz(a)anthracene (DMBA)-induced breast cancer model. Female Sprague-Dawley rats were fed a low-fat, a high corn-oil or a high extra-virgin olive oil (EVOO) diet from weaning or from induction with DMBA. In mammary glands and tumors we analyzed global and gene specific (RASSF1A, TIMP3) DNA methylation by LUMA and bisulfite pyrosequencing assays, respectively. We also determined gene expression and enzymatic activity of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b) and evaluated changes in histone modifications (H3K4me2, H3K27me3, H4K20me3 and H4K16ac) by western-blot. Our results showed variations along time in the global DNA methylation of the mammary gland displaying decreases at puberty and with aging. The olive oil-enriched diet, on the one hand, increased the levels of global DNA methylation in mammary gland and tumor, and on the other, changed histone modifications patterns. The corn oil-enriched diet increased DNA methyltransferase activity in both tissues, resulting in an increase in the promoter methylation of the tumor suppressor genes RASSF1A and TIMP3. These results suggest a differential effect of the high fat diets on epigenetic patterns with a relevant role in the neoplastic transformation, which could be one of the mechanisms of their differential promoter effect, clearly stimulating for the high corn-oil diet and with a weaker influence for the high EVOO diet, on breast cancer progression.

Gene Expression Profiling Reveals a Massive, Aneuploidy-Dependent Transcriptional Deregulation and Distinct Differences between Lymph Node–Negative and Lymph Node–Positive Colon Carcinomas

PubMed Central

Grade, Marian; Hörmann, Patrick; Becker, Sandra; Hummon, Amanda B.; Wangsa, Danny; Varma, Sudhir; Simon, Richard; Liersch, Torsten; Becker, Heinz; Difilippantonio, Michael J.; Ghadimi, B. Michael; Ried, Thomas

2016-01-01

To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P < 1e–7). A significant proportion of these genes mapped to chromosome 20 (P = 0.01). Seventeen genes had a >5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node–negative and lymph node–positive tumors (P < 0.001), the functional annotation of which revealed a preponderance of genes that play a role in cellular immune response and surveillance. The microarray-derived gene expression levels of 20 deregulated genes were validated using quantitative real-time reverse transcription-PCR in >40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/β-catenin signaling cascade, suggesting similar pathogenic pathways. PMID:17210682

Gene expression profiling reveals a massive, aneuploidy-dependent transcriptional deregulation and distinct differences between lymph node-negative and lymph node-positive colon carcinomas.

PubMed

Grade, Marian; Hörmann, Patrick; Becker, Sandra; Hummon, Amanda B; Wangsa, Danny; Varma, Sudhir; Simon, Richard; Liersch, Torsten; Becker, Heinz; Difilippantonio, Michael J; Ghadimi, B Michael; Ried, Thomas

2007-01-01

To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P < 1e-7). A significant proportion of these genes mapped to chromosome 20 (P = 0.01). Seventeen genes had a >5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node-negative and lymph node-positive tumors (P < 0.001), the functional annotation of which revealed a preponderance of genes that play a role in cellular immune response and surveillance. The microarray-derived gene expression levels of 20 deregulated genes were validated using quantitative real-time reverse transcription-PCR in >40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/beta-catenin signaling cascade, suggesting similar pathogenic pathways.

Size-dependent regulation of dorsal-ventral patterning in the early Drosophila embryo

PubMed Central

Garcia, Mayra; Nahmad, Marcos; Reeves, Gregory T.; Stathopoulos, Angelike

2013-01-01

How natural variation in embryo size affects patterning of the Drosophila embryo dorsal-ventral (DV) axis is not known. Here we examined quantitatively the relationship between nuclear distribution of the Dorsal transcription factor, boundary positions for several target genes, and DV axis length. Data were obtained from embryos of a wild-type background as well as from mutant lines inbred to size select embryos of smaller or larger sizes. Our data show that the width of the nuclear Dorsal gradient correlates with DV axis length. In turn, for some genes expressed along the DV axis, the boundary positions correlate closely with nuclear Dorsal levels and with DV axis length; while the expression pattern of others is relatively constant and independent of the width of the Dorsal gradient. In particular, the patterns of snail (sna) and ventral nervous-system defective (vnd) correlate with nuclear Dorsal levels and exhibit scaling to DV length; while the pattern of intermediate neuroblasts defective (ind) remains relatively constant with respect to changes in Dorsal and DV length. However, in mutants that exhibit an abnormal expansion of the Dorsal gradient which fails to scale to DV length, only sna follows the Dorsal distribution and exhibits overexpansion; in contrast, vnd and ind do not overexpand suggesting some additional mechanism acts to refine the dorsal boundaries of these two genes. Thus, our results argue against the idea that the Dorsal gradient works as a global system of relative coordinates along the DV axis and suggest that individual targets respond to changes in embryo size in a gene-specific manner. PMID:23800450

Whole-Genome Microarray and Gene Deletion Studies Reveal Regulation of the Polyhydroxyalkanoate Production Cycle by the Stringent Response in Ralstonia eutropha H16

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brigham, CJ; Speth, DR; Rha, C

Poly(3-hydroxybutyrate) (PHB) production and mobilization in Ralstonia eutropha are well studied, but in only a few instances has PHB production been explored in relation to other cellular processes. We examined the global gene expression of wild-type R. eutropha throughout the PHB cycle: growth on fructose, PHB production using fructose following ammonium depletion, and PHB utilization in the absence of exogenous carbon after ammonium was resupplied. Our results confirm or lend support to previously reported results regarding the expression of PHB-related genes and enzymes. Additionally, genes for many different cellular processes, such as DNA replication, cell division, and translation, are selectivelymore » repressed during PHB production. In contrast, the expression levels of genes under the control of the alternative sigma factor sigma(54) increase sharply during PHB production and are repressed again during PHB utilization. Global gene regulation during PHB production is strongly reminiscent of the gene expression pattern observed during the stringent response in other species. Furthermore, a ppGpp synthase deletion mutant did not show an accumulation of PHB, and the chemical induction of the stringent response with DL-norvaline caused an increased accumulation of PHB in the presence of ammonium. These results indicate that the stringent response is required for PHB accumulation in R. eutropha, helping to elucidate a thus-far-unknown physiological basis for this process.« less

Express path analysis identifies a tyrosine kinase Src-centric network regulating divergent host responses to Mycobacterium tuberculosis infection.

PubMed

Karim, Ahmad Faisal; Chandra, Pallavi; Chopra, Aanchal; Siddiqui, Zaved; Bhaskar, Ashima; Singh, Amit; Kumar, Dhiraj

2011-11-18

Global gene expression profiling has emerged as a major tool in understanding complex response patterns of biological systems to perturbations. However, a lack of unbiased analytical approaches has restricted the utility of complex microarray data to gain novel system level insights. Here we report a strategy, express path analysis (EPA), that helps to establish various pathways differentially recruited to achieve specific cellular responses under contrasting environmental conditions in an unbiased manner. The analysis superimposes differentially regulated genes between contrasting environments onto the network of functional protein associations followed by a series of iterative enrichments and network analysis. To test the utility of the approach, we infected THP1 macrophage cells with a virulent Mycobacterium tuberculosis strain (H37Rv) or the attenuated non-virulent strain H37Ra as contrasting perturbations and generated the temporal global expression profiles. EPA of the results provided details of response-specific and time-dependent host molecular network perturbations. Further analysis identified tyrosine kinase Src as the major regulatory hub discriminating the responses between wild-type and attenuated Mtb infection. We were then able to verify this novel role of Src experimentally and show that Src executes its role through regulating two vital antimicrobial processes of the host cells (i.e. autophagy and acidification of phagolysosome). These results bear significant potential for developing novel anti-tuberculosis therapy. We propose that EPA could prove extremely useful in understanding complex cellular responses for a variety of perturbations, including pathogenic infections.

A global analysis of the complex landscape of isoforms and regulatory networks of p63 in human cells and tissues.

PubMed

Sethi, Isha; Romano, Rose-Anne; Gluck, Christian; Smalley, Kirsten; Vojtesek, Borivoj; Buck, Michael J; Sinha, Satrajit

2015-08-07

The transcription factor p63 belongs to the p53/p63/p73 family and plays key functional roles during normal epithelial development and differentiation and in pathological states such as squamous cell carcinomas. The human TP63 gene, located on chromosome 3q28 is driven by two promoters that generate the full-length transactivating (TA) and N-terminal truncated (ΔN) isoforms. Furthermore alternative splicing at the C-terminus gives rise to additional α, β, γ and likely several other minor variants. Teasing out the expression and biological function of each p63 variant has been both the focus of, and a cause for contention in the p63 field. Here we have taken advantage of a burgeoning RNA-Seq based genomic data-sets to examine the global expression profiles of p63 isoforms across commonly utilized human cell-lines and major tissues and organs. Consistent with earlier studies, we find ΔNp63 transcripts, primarily that of the ΔNp63α isoforms, to be expressed in most cells of epithelial origin such as those of skin and oral tissues, mammary glands and squamous cell carcinomas. In contrast, TAp63 is not expressed in the majority of normal cell-types and tissues; rather it is selectively expressed at moderate to high levels in a subset of Burkitt's and diffuse large B-cell lymphoma cell lines. We verify this differential expression pattern of p63 isoforms by Western blot analysis, using newly developed ΔN and TA specific antibodies. Furthermore using unsupervised clustering of human cell lines, tissues and organs, we show that ΔNp63 and TAp63 driven transcriptional networks involve very distinct sets of molecular players, which may underlie their different biological functions. In this study we report comprehensive and global expression profiles of p63 isoforms and their relationship to p53/p73 and other potential transcriptional co-regulators. We curate publicly available data generated in part by consortiums such as ENCODE, FANTOM and Human Protein Atlas to delineate the vastly different transcriptomic landscapes of ΔNp63 and TAp63. Our studies help not only in dispelling prevailing myths and controversies on p63 expression in commonly used human cell lines but also augur new isoform- and cell type-specific activities of p63.

78 FR 18376 - Promotional Rates for Global Express Guaranteed Service

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... POSTAL SERVICE Promotional Rates for Global Express Guaranteed Service AGENCY: Postal Service\\TM\\. ACTION: Notice of Promotional Rates. SUMMARY: The Postal Service gives notice of promotional rates for Global Express Guaranteed[supreg] (GXG[supreg]) service consistent with Governors' Decision No. 12-02...

A Network of Networks Perspective on Global Trade.

PubMed

Maluck, Julian; Donner, Reik V

2015-01-01

Mutually intertwined supply chains in contemporary economy result in a complex network of trade relationships with a highly non-trivial topology that varies with time. In order to understand the complex interrelationships among different countries and economic sectors, as well as their dynamics, a holistic view on the underlying structural properties of this network is necessary. This study employs multi-regional input-output data to decompose 186 national economies into 26 industry sectors and utilizes the approach of interdependent networks to analyze the substructure of the resulting international trade network for the years 1990-2011. The partition of the network into national economies is observed to be compatible with the notion of communities in the sense of complex network theory. By studying internal versus cross-subgraph contributions to established complex network metrics, new insights into the architecture of global trade are obtained, which allow to identify key elements of global economy. Specifically, financial services and business activities dominate domestic trade whereas electrical and machinery industries dominate foreign trade. In order to further specify each national sector's role individually, (cross-)clustering coefficients and cross-betweenness are obtained for different pairs of subgraphs. The corresponding analysis reveals that specific industrial sectors tend to favor distinct directionality patterns and that the cross-clustering coefficient for geographically close country pairs is remarkably high, indicating that spatial factors are still of paramount importance for the organization of trade patterns in modern economy. Regarding the evolution of the trade network's substructure, globalization is well-expressed by trends of several structural characteristics (e.g., link density and node strength) in the interacting network framework. Extreme events, such as the financial crisis 2008/2009, are manifested as anomalies superimposed to these trends. The marked reorganization of trade patterns, associated with this economic crisis in comparison to "normal" annual fluctuations in the network structure is traced and quantified by a new widely applicable generalization of the Hamming distance to weighted networks.

A Network of Networks Perspective on Global Trade

PubMed Central

Maluck, Julian; Donner, Reik V.

2015-01-01

Mutually intertwined supply chains in contemporary economy result in a complex network of trade relationships with a highly non-trivial topology that varies with time. In order to understand the complex interrelationships among different countries and economic sectors, as well as their dynamics, a holistic view on the underlying structural properties of this network is necessary. This study employs multi-regional input-output data to decompose 186 national economies into 26 industry sectors and utilizes the approach of interdependent networks to analyze the substructure of the resulting international trade network for the years 1990–2011. The partition of the network into national economies is observed to be compatible with the notion of communities in the sense of complex network theory. By studying internal versus cross-subgraph contributions to established complex network metrics, new insights into the architecture of global trade are obtained, which allow to identify key elements of global economy. Specifically, financial services and business activities dominate domestic trade whereas electrical and machinery industries dominate foreign trade. In order to further specify each national sector’s role individually, (cross-)clustering coefficients and cross-betweenness are obtained for different pairs of subgraphs. The corresponding analysis reveals that specific industrial sectors tend to favor distinct directionality patterns and that the cross-clustering coefficient for geographically close country pairs is remarkably high, indicating that spatial factors are still of paramount importance for the organization of trade patterns in modern economy. Regarding the evolution of the trade network’s substructure, globalization is well-expressed by trends of several structural characteristics (e.g., link density and node strength) in the interacting network framework. Extreme events, such as the financial crisis 2008/2009, are manifested as anomalies superimposed to these trends. The marked reorganization of trade patterns, associated with this economic crisis in comparison to “normal” annual fluctuations in the network structure is traced and quantified by a new widely applicable generalization of the Hamming distance to weighted networks. PMID:26197439

The Determination of Children's Knowledge of Global Lunar Patterns from Online Essays Using Text Mining Analysis

ERIC Educational Resources Information Center

Cheon, Jongpil; Lee, Sangno; Smith, Walter; Song, Jaeki; Kim, Yongjin

2013-01-01

The purpose of this study was to use text mining analysis of early adolescents' online essays to determine their knowledge of global lunar patterns. Australian and American students in grades five to seven wrote about global lunar patterns they had discovered by sharing observations with each other via the Internet. These essays were analyzed for…

Regional mantle upwelling on Venus: The Beta-Atla-Themis anomaly and correlation with global tectonic patterns

NASA Technical Reports Server (NTRS)

Crumpler, L. S.; Head, J. W.; Aubele, Jayne C.

1993-01-01

The morphology and global distribution of volcanic centers and their association with other geological characteristics offers significant insight into the global patterns of geology, tectonic style, thermal state, and interior dynamics of Venus. Magellan data permit the detailed geological interpretation necessary to address questions about interior dynamics of Venus particularly as they reflect relatively physical, chemical, and thermal conditions of the interior. This paper focuses on the distribution of anomalous concentrations of volcanic centers on Venus and regional patterns of tectonic deformation as it may relate to the identification of global internal anomalies, including mantle dynamic, petrological, or thermal patterns.

MRNA and miRNA expression patterns associated to pathways linked to metal mixture health effects.

PubMed

Martínez-Pacheco, M; Hidalgo-Miranda, A; Romero-Córdoba, S; Valverde, M; Rojas, E

2014-01-10

Metals are a threat to human health by increasing disease risk. Experimental data have linked altered miRNA expression with exposure to some metals. MiRNAs comprise a large family of non-coding single-stranded molecules that primarily function to negatively regulate gene expression post-transcriptionally. Although several human populations are exposed to low concentrations of As, Cd and Pb as a mixture, most toxicology research focuses on the individual effects that these metals exert. Thus, this study aims to evaluate global miRNA and mRNA expression changes induced by a metal mixture containing NaAsO2, CdCl2, Pb(C2H3O2)2·3H2O and to predict possible metal-associated disease development under these conditions. Our results show that this metal mixture results in a miRNA expression profile that may be responsible for the mRNA expression changes observed under experimental conditions in which coding proteins are involved in cellular processes, including cell death, growth and proliferation related to the metal-associated inflammatory response and cancer. © 2013 Elsevier B.V. All rights reserved.

Transcriptomic analysis provides insight into high-altitude acclimation in domestic goats.

PubMed

Tang, Qianzi; Huang, Wenyao; Guan, Jiuqiang; Jin, Long; Che, Tiandong; Fu, Yuhua; Hu, Yaodong; Tian, Shilin; Wang, Dawei; Jiang, Zhi; Li, Xuewei; Li, Mingzhou

2015-08-10

Domestic goats are distributed in a wide range of habitats and have acclimated to their local environmental conditions. To investigate the gene expression changes of goats that are induced by high altitude stress, we performed RNA-seq on 27 samples from the three hypoxia-sensitive tissues (heart, lung, and skeletal muscle) in three indigenous populations from distinct altitudes (600 m, 2000 m, and 3000 m). We generated 129Gb of high-quality sequencing data (~4Gb per sample) and catalogued the expression profiles of 12,421 annotated hircine genes in each sample. The analysis showed global similarities and differences of high-altitude transcriptomes among populations and tissues as well as revealed that the heart underwent the most high-altitude induced expression changes. We identified numerous differentially expressed genes that exhibited distinct expression patterns, and nonsynonymous single nucleotide variant-containing genes that were highly differentiated between the high- and low-altitude populations. These genes have known or potential roles in hypoxia response and were enriched in functional gene categories potentially responsible for high-altitude stress. Therefore, they are appealing candidates for further investigation of the gene expression and associated regulatory mechanisms related to high-altitude acclimation. Copyright © 2015 Elsevier B.V. All rights reserved.

Expression profiling reveals Spot 42 small RNA as a key regulator in the central metabolism of Aliivibrio salmonicida

PubMed Central

2012-01-01

Background Spot 42 was discovered in Escherichia coli nearly 40 years ago as an abundant, small and unstable RNA. Its biological role has remained obscure until recently, and is today implicated in having broader roles in the central and secondary metabolism. Spot 42 is encoded by the spf gene. The gene is ubiquitous in the Vibrionaceae family of gamma-proteobacteria. One member of this family, Aliivibrio salmonicida, causes cold-water vibriosis in farmed Atlantic salmon. Its genome encodes Spot 42 with 84% identity to E. coli Spot 42. Results We generated a A. salmonicida spf deletion mutant. We then used microarray and Northern blot analyses to monitor global effects on the transcriptome in order to provide insights into the biological roles of Spot 42 in this bacterium. In the presence of glucose, we found a surprisingly large number of ≥ 2X differentially expressed genes, and several major cellular processes were affected. A gene encoding a pirin-like protein showed an on/off expression pattern in the presence/absence of Spot 42, which suggests that Spot 42 plays a key regulatory role in the central metabolism by regulating the switch between fermentation and respiration. Interestingly, we discovered an sRNA named VSsrna24, which is encoded immediately downstream of spf. This new sRNA has an expression pattern opposite to that of Spot 42, and its expression is repressed by glucose. Conclusions We hypothesize that Spot 42 plays a key role in the central metabolism, in part by regulating the pyruvat dehydrogenase enzyme complex via pirin. PMID:22272603

Arabidopsis whole-transcriptome profiling defines the features of coordinated regulations that occur during secondary growth.

PubMed

Ko, Jae-Heung; Han, Kyung-Hwan

2004-05-01

Secondary growth in the inflorescence stems of Arabidopsis plants was induced by a combination of short-day and long-day treatments. The induced stems were divided into three different stem developmental stages (i.e., immature, intermediate, and mature) with regard to secondary growth. Whole transcriptome microarrays were used to examine the changes in global gene expression occurring at the different stem developmental stages. Over 70% of the Arabidopsis transcriptome was expressed in the stem tissues. In the mature stems with secondary growth, 567 genes were upregulated 5-fold or higher and 530 were downregulated, when compared to immature stems (with no secondary growth) and 10-day old seedlings (with no inflorescence stem). The transcription phenotypes obtained from the stems at different developmental stages largely confirm the existing insights into the biochemical processes involved in the sequential events that lead to wood formation. The major difference found between the stems undergoing secondary growth and only primary growth was in the expression profiles of transcriptional regulation-and signal transduction-related genes. An analysis of several shoot apical meristem (SAM) activity-related gene expression patterns in the stems indicated that the genetic control of secondary meristem activity might be governed by a different mechanism from that of SAM. The current study established the expression patterns of many unknown genes and identified candidate genes that are involved in the genetic regulation of secondary growth. The findings described in this report should improve our understanding of the molecular mechanisms that regulate the growth and development of the stem.

Widespread antisense transcription of Populus genome under drought.

PubMed

Yuan, Yinan; Chen, Su

2018-06-06

Antisense transcription is widespread in many genomes and plays important regulatory roles in gene expression. The objective of our study was to investigate the extent and functional relevance of antisense transcription in forest trees. We employed Populus, a model tree species, to probe the antisense transcriptional response of tree genome under drought, through stranded RNA-seq analysis. We detected nearly 48% of annotated Populus gene loci with antisense transcripts and 44% of them with co-transcription from both DNA strands. Global distribution of reads pattern across annotated gene regions uncovered that antisense transcription was enriched in untranslated regions while sense reads were predominantly mapped in coding exons. We further detected 1185 drought-responsive sense and antisense gene loci and identified a strong positive correlation between the expression of antisense and sense transcripts. Additionally, we assessed the antisense expression in introns and found a strong correlation between intronic expression and exonic expression, confirming antisense transcription of introns contributes to transcriptional activity of Populus genome under drought. Finally, we functionally characterized drought-responsive sense-antisense transcript pairs through gene ontology analysis and discovered that functional groups including transcription factors and histones were concordantly regulated at both sense and antisense transcriptional level. Overall, our study demonstrated the extensive occurrence of antisense transcripts of Populus genes under drought and provided insights into genome structure, regulation pattern and functional significance of drought-responsive antisense genes in forest trees. Datasets generated in this study serve as a foundation for future genetic analysis to improve our understanding of gene regulation by antisense transcription.

Differential Expression Patterns in Chemosensory and Non-Chemosensory Tissues of Putative Chemosensory Genes Identified by Transcriptome Analysis of Insect Pest the Purple Stem Borer Sesamia inferens (Walker)

PubMed Central

Zhang, Ya-Nan; Jin, Jun-Yan; Jin, Rong; Xia, Yi-Han; Zhou, Jing-Jiang; Deng, Jian-Yu; Dong, Shuang-Lin

2013-01-01

Background A large number of insect chemosensory genes from different gene subfamilies have been identified and annotated, but their functional diversity and complexity are largely unknown. A systemic examination of expression patterns in chemosensory organs could provide important information. Methodology/Principal Findings We identified 92 putative chemosensory genes by analysing the transcriptome of the antennae and female sex pheromone gland of the purple stem borer Sesamia inferens, among them 87 are novel in this species, including 24 transcripts encoding for odorant binding proteins (OBPs), 24 for chemosensory proteins (CSPs), 2 for sensory neuron membrane proteins (SNMPs), 39 for odorant receptors (ORs) and 3 for ionotropic receptors (IRs). The transcriptome analyses were validated and quantified with a detailed global expression profiling by Reverse Transcription-PCR for all 92 transcripts and by Quantitative Real Time RT-PCR for selected 16 ones. Among the chemosensory gene subfamilies, CSP transcripts are most widely and evenly expressed in different tissues and stages, OBP transcripts showed a clear antenna bias and most of OR transcripts are only detected in adult antennae. Our results also revealed that some OR transcripts, such as the transcripts of SNMP2 and 2 IRs were expressed in non-chemosensory tissues, and some CSP transcripts were antenna-biased expression. Furthermore, no chemosensory transcript is specific to female sex pheromone gland and very few are found in the heads. Conclusion Our study revealed that there are a large number of chemosensory genes expressed in S. inferens, and some of them displayed unusual expression profile in non-chemosensory tissues. The identification of a large set of putative chemosensory genes of each subfamily from a single insect species, together with their different expression profiles provide further information in understanding the functions of these chemosensory genes in S. inferens as well as other insects. PMID:23894529

Differential expression patterns in chemosensory and non-chemosensory tissues of putative chemosensory genes identified by transcriptome analysis of insect pest the purple stem borer Sesamia inferens (Walker).

PubMed

Zhang, Ya-Nan; Jin, Jun-Yan; Jin, Rong; Xia, Yi-Han; Zhou, Jing-Jiang; Deng, Jian-Yu; Dong, Shuang-Lin

2013-01-01

A large number of insect chemosensory genes from different gene subfamilies have been identified and annotated, but their functional diversity and complexity are largely unknown. A systemic examination of expression patterns in chemosensory organs could provide important information. We identified 92 putative chemosensory genes by analysing the transcriptome of the antennae and female sex pheromone gland of the purple stem borer Sesamia inferens, among them 87 are novel in this species, including 24 transcripts encoding for odorant binding proteins (OBPs), 24 for chemosensory proteins (CSPs), 2 for sensory neuron membrane proteins (SNMPs), 39 for odorant receptors (ORs) and 3 for ionotropic receptors (IRs). The transcriptome analyses were validated and quantified with a detailed global expression profiling by Reverse Transcription-PCR for all 92 transcripts and by Quantitative Real Time RT-PCR for selected 16 ones. Among the chemosensory gene subfamilies, CSP transcripts are most widely and evenly expressed in different tissues and stages, OBP transcripts showed a clear antenna bias and most of OR transcripts are only detected in adult antennae. Our results also revealed that some OR transcripts, such as the transcripts of SNMP2 and 2 IRs were expressed in non-chemosensory tissues, and some CSP transcripts were antenna-biased expression. Furthermore, no chemosensory transcript is specific to female sex pheromone gland and very few are found in the heads. Our study revealed that there are a large number of chemosensory genes expressed in S. inferens, and some of them displayed unusual expression profile in non-chemosensory tissues. The identification of a large set of putative chemosensory genes of each subfamily from a single insect species, together with their different expression profiles provide further information in understanding the functions of these chemosensory genes in S. inferens as well as other insects.

Evidence for a role of the oxytocin system, indexed by genetic variation in CD38, in the social bonding effects of expressed gratitude

PubMed Central

2014-01-01

Oxytocin is thought to play a central role in promoting close social bonds via influence on social interactions. The current investigation targeted interactions involving expressed gratitude between members of romantic relationships because recent evidence suggests gratitude and its expression provides behavioral and psychological ‘glue’ to bind individuals closer together. Specifically, we took a genetic approach to test the hypothesis that social interactions involving expressed gratitude would be associated with variation in a gene, CD38, which has been shown to affect oxytocin secretion. A polymorphism (rs6449182) that affects CD38 expression was significantly associated with global relationship satisfaction, perceived partner responsiveness and positive emotions (particularly love) after lab-based interactions, observed behavioral expression of gratitude toward a romantic partner in the lab, and frequency of expressed gratitude in daily life. A separate polymorphism in CD38 (rs3796863) previously associated with plasma oxytocin levels and social engagement was also associated with perceived responsiveness in the benefactor after an expression of gratitude. The combined influence of the two polymorphisms was associated with a broad range of gratitude-related behaviors and feelings. The consistent pattern of findings suggests that the oxytocin system is associated with solidifying the glue that binds adults into meaningful and important relationships. PMID:24396004

The expression of proinflammatory genes in epidermal keratinocytes is regulated by hydration status.

PubMed

Xu, Wei; Jia, Shengxian; Xie, Ping; Zhong, Aimei; Galiano, Robert D; Mustoe, Thomas A; Hong, Seok J

2014-04-01

Mucosal wounds heal more rapidly, exhibit less inflammation, and are associated with minimal scarring when compared with equivalent cutaneous wounds. We previously demonstrated that cutaneous epithelium exhibits an exaggerated response to injury compared with mucosal epithelium. We hypothesized that treatment of injured skin with a semiocclusive dressing preserves the hydration of the skin and results in a wound healing phenotype that more closely resembles that of mucosa. Here we explored whether changes in hydration status alter epidermal gene expression patterns in rabbit partial-thickness incisional wounds. Using microarray studies on injured epidermis, we showed that global gene expression patterns in highly occluded versus non-occluded wounds are distinct. Many genes including IL-1β, IL-8, TNF-α (tumor necrosis factor-α), and COX-2 (cyclooxygenase 2) are upregulated in non-occluded wounds compared with highly occluded wounds. In addition, decreased levels of hydration resulted in an increased expression of proinflammatory genes in human ex vivo skin culture (HESC) and stratified keratinocytes. Hierarchical analysis of genes using RNA interference showed that both TNF-α and IL-1β regulate the expression of IL-8 through independent pathways in response to reduced hydration. Furthermore, both gene knockdown and pharmacological inhibition studies showed that COX-2 mediates the TNF-α/IL-8 pathway by increasing the production of prostaglandin E2 (PGE2). IL-8 in turn controls the production of matrix metalloproteinase-9 in keratinocytes. Our data show that hydration status directly affects the expression of inflammatory signaling in the epidermis. The identification of genes involved in the epithelial hydration pathway provides an opportunity to develop strategies to reduce scarring and optimize wound healing.

Gene expression networks underlying ovarian development in wild largemouth bass (Micropterus salmoides).

PubMed

Martyniuk, Christopher J; Prucha, Melinda S; Doperalski, Nicholas J; Antczak, Philipp; Kroll, Kevin J; Falciani, Francesco; Barber, David S; Denslow, Nancy D

2013-01-01

Oocyte maturation in fish involves numerous cell signaling cascades that are activated or inhibited during specific stages of oocyte development. The objectives of this study were to characterize molecular pathways and temporal gene expression patterns throughout a complete breeding cycle in wild female largemouth bass to improve understanding of the molecular sequence of events underlying oocyte maturation. Transcriptomic analysis was performed on eight morphologically diverse stages of the ovary, including primary and secondary stages of oocyte growth, ovulation, and atresia. Ovary histology, plasma vitellogenin, 17β-estradiol, and testosterone were also measured to correlate with gene networks. Global expression patterns revealed dramatic differences across ovarian development, with 552 and 2070 genes being differentially expressed during both ovulation and atresia respectively. Gene set enrichment analysis (GSEA) revealed that early primary stages of oocyte growth involved increases in expression of genes involved in pathways of B-cell and T-cell receptor-mediated signaling cascades and fibronectin regulation. These pathways as well as pathways that included adrenergic receptor signaling, sphingolipid metabolism and natural killer cell activation were down-regulated at ovulation. At atresia, down-regulated pathways included gap junction and actin cytoskeleton regulation, gonadotrope and mast cell activation, and vasopressin receptor signaling and up-regulated pathways included oxidative phosphorylation and reactive oxygen species metabolism. Expression targets for luteinizing hormone signaling were low during vitellogenesis but increased 150% at ovulation. Other networks found to play a significant role in oocyte maturation included those with genes regulated by members of the TGF-beta superfamily (activins, inhibins, bone morphogenic protein 7 and growth differentiation factor 9), neuregulin 1, retinoid X receptor, and nerve growth factor family. This study offers novel insight into the gene networks underlying vitellogenesis, ovulation and atresia and generates new hypotheses about the cellular pathways regulating oocyte maturation.

Genome-wide organization and expression profiling of the R2R3-MYB transcription factor family in pineapple (Ananas comosus).

PubMed

Liu, Chaoyang; Xie, Tao; Chen, Chenjie; Luan, Aiping; Long, Jianmei; Li, Chuhao; Ding, Yaqi; He, Yehua

2017-07-01

The MYB proteins comprise one of the largest families of plant transcription factors, which are involved in various plant physiological and biochemical processes. Pineapple (Ananas comosus) is one of three most important tropical fruits worldwide. The completion of pineapple genome sequencing provides a great opportunity to investigate the organization and evolutionary traits of pineapple MYB genes at the genome-wide level. In the present study, a total of 94 pineapple R2R3-MYB genes were identified and further phylogenetically classified into 26 subfamilies, as supported by the conserved gene structures and motif composition. Collinearity analysis indicated that the segmental duplication events played a crucial role in the expansion of pineapple MYB gene family. Further comparative phylogenetic analysis suggested that there have been functional divergences of MYB gene family during plant evolution. RNA-seq data from different tissues and developmental stages revealed distinct temporal and spatial expression profiles of the AcMYB genes. Further quantitative expression analysis showed the specific expression patterns of the selected putative stress-related AcMYB genes in response to distinct abiotic stress and hormonal treatments. The comprehensive expression analysis of the pineapple MYB genes, especially the tissue-preferential and stress-responsive genes, could provide valuable clues for further function characterization. In this work, we systematically identified AcMYB genes by analyzing the pineapple genome sequence using a set of bioinformatics approaches. Our findings provide a global insight into the organization, phylogeny and expression patterns of the pineapple R2R3-MYB genes, and hence contribute to the greater understanding of their biological roles in pineapple.

Alternate Bearing in Citrus: Changes in the Expression of Flowering Control Genes and in Global Gene Expression in ON- versus OFF-Crop Trees

PubMed Central

Shalom, Liron; Samuels, Sivan; Zur, Naftali; Shlizerman, Lyudmila; Zemach, Hanita; Weissberg, Mira; Ophir, Ron; Blumwald, Eduardo; Sadka, Avi

2012-01-01

Alternate bearing (AB) is the process in fruit trees by which cycles of heavy yield (ON crop) one year are followed by a light yield (OFF crop) the next. Heavy yield usually reduces flowering intensity the following year. Despite its agricultural importance, how the developing crop influences the following year's return bloom and yield is not fully understood. It might be assumed that an ‘AB signal’ is generated in the fruit, or in another organ that senses fruit presence, and moves into the bud to determine its fate—flowering or vegetative growth. The bud then responds to fruit presence by altering regulatory and metabolic pathways. Determining these pathways, and when they are altered, might indicate the nature of this putative AB signal. We studied bud morphology, the expression of flowering control genes, and global gene expression in ON- and OFF-crop buds. In May, shortly after flowering and fruit set, OFF-crop buds were already significantly longer than ON-crop buds. The number of differentially expressed genes was higher in May than at the other tested time points. Processes differentially expressed between ON- and OFF-crop trees included key metabolic and regulatory pathways, such as photosynthesis and secondary metabolism. The expression of genes of trehalose metabolism and flavonoid metabolism was validated by nCounter technology, and the latter was confirmed by metabolomic analysis. Among genes induced in OFF-crop trees was one homologous to SQUAMOSA PROMOTER BINDING-LIKE (SPL), which controls juvenile-to-adult and annual phase transitions, regulated by miR156. The expression pattern of SPL-like, miR156 and other flowering control genes suggested that fruit load affects bud fate, and therefore development and metabolism, a relatively long time before the flowering induction period. Results shed light on some of the metabolic and regulatory processes that are altered in ON and OFF buds. PMID:23071667

Alternate bearing in citrus: changes in the expression of flowering control genes and in global gene expression in ON- versus OFF-crop trees.

PubMed

Shalom, Liron; Samuels, Sivan; Zur, Naftali; Shlizerman, Lyudmila; Zemach, Hanita; Weissberg, Mira; Ophir, Ron; Blumwald, Eduardo; Sadka, Avi

2012-01-01

Alternate bearing (AB) is the process in fruit trees by which cycles of heavy yield (ON crop) one year are followed by a light yield (OFF crop) the next. Heavy yield usually reduces flowering intensity the following year. Despite its agricultural importance, how the developing crop influences the following year's return bloom and yield is not fully understood. It might be assumed that an 'AB signal' is generated in the fruit, or in another organ that senses fruit presence, and moves into the bud to determine its fate-flowering or vegetative growth. The bud then responds to fruit presence by altering regulatory and metabolic pathways. Determining these pathways, and when they are altered, might indicate the nature of this putative AB signal. We studied bud morphology, the expression of flowering control genes, and global gene expression in ON- and OFF-crop buds. In May, shortly after flowering and fruit set, OFF-crop buds were already significantly longer than ON-crop buds. The number of differentially expressed genes was higher in May than at the other tested time points. Processes differentially expressed between ON- and OFF-crop trees included key metabolic and regulatory pathways, such as photosynthesis and secondary metabolism. The expression of genes of trehalose metabolism and flavonoid metabolism was validated by nCounter technology, and the latter was confirmed by metabolomic analysis. Among genes induced in OFF-crop trees was one homologous to SQUAMOSA PROMOTER BINDING-LIKE (SPL), which controls juvenile-to-adult and annual phase transitions, regulated by miR156. The expression pattern of SPL-like, miR156 and other flowering control genes suggested that fruit load affects bud fate, and therefore development and metabolism, a relatively long time before the flowering induction period. Results shed light on some of the metabolic and regulatory processes that are altered in ON and OFF buds.

The Fisher-Markov selector: fast selecting maximally separable feature subset for multiclass classification with applications to high-dimensional data.

PubMed

Cheng, Qiang; Zhou, Hongbo; Cheng, Jie

2011-06-01

Selecting features for multiclass classification is a critically important task for pattern recognition and machine learning applications. Especially challenging is selecting an optimal subset of features from high-dimensional data, which typically have many more variables than observations and contain significant noise, missing components, or outliers. Existing methods either cannot handle high-dimensional data efficiently or scalably, or can only obtain local optimum instead of global optimum. Toward the selection of the globally optimal subset of features efficiently, we introduce a new selector--which we call the Fisher-Markov selector--to identify those features that are the most useful in describing essential differences among the possible groups. In particular, in this paper we present a way to represent essential discriminating characteristics together with the sparsity as an optimization objective. With properly identified measures for the sparseness and discriminativeness in possibly high-dimensional settings, we take a systematic approach for optimizing the measures to choose the best feature subset. We use Markov random field optimization techniques to solve the formulated objective functions for simultaneous feature selection. Our results are noncombinatorial, and they can achieve the exact global optimum of the objective function for some special kernels. The method is fast; in particular, it can be linear in the number of features and quadratic in the number of observations. We apply our procedure to a variety of real-world data, including mid--dimensional optical handwritten digit data set and high-dimensional microarray gene expression data sets. The effectiveness of our method is confirmed by experimental results. In pattern recognition and from a model selection viewpoint, our procedure says that it is possible to select the most discriminating subset of variables by solving a very simple unconstrained objective function which in fact can be obtained with an explicit expression.

The environmental roots of non-communicable diseases (NCDs) and the epigenetic impacts of globalization.

PubMed

Vineis, Paolo; Stringhini, Silvia; Porta, Miquel

2014-08-01

Non-communicable diseases (NCDs) are increasing worldwide. We hypothesize that environmental factors (including social adversity, diet, lack of physical activity and pollution) can become "embedded" in the biology of humans. We also hypothesize that the "embedding" partly occurs because of epigenetic changes, i.e., durable changes in gene expression patterns. Our concern is that once such factors have a foundation in human biology, they can affect human health (including NCDs) over a long period of time and across generations. To analyze how worldwide changes in movements of goods, persons and lifestyles (globalization) may affect the "epigenetic landscape" of populations and through this have an impact on NCDs. We provide examples of such changes and effects by discussing the potential epigenetic impact of socio-economic status, migration, and diet, as well as the impact of environmental factors influencing trends in age at puberty. The study of durable changes in epigenetic patterns has the potential to influence policy and practice; for example, by enabling stratification of populations into those who could particularly benefit from early interventions to prevent NCDs, or by demonstrating mechanisms through which environmental factors influence disease risk, thus providing compelling evidence for policy makers, companies and the civil society at large. The current debate on the '25 × 25 strategy', a goal of 25% reduction in relative mortality from NCDs by 2025, makes the proposed approach even more timely. Epigenetic modifications related to globalization may crucially contribute to explain current and future patterns of NCDs, and thus deserve attention from environmental researchers, public health experts, policy makers, and concerned citizens. Copyright © 2014 Elsevier Inc. All rights reserved.

Proteomics Analysis of Human Skeletal Muscle Reveals Novel Abnormalities in Obesity and Type 2 Diabetes

PubMed Central

Hwang, Hyonson; Bowen, Benjamin P.; Lefort, Natalie; Flynn, Charles R.; De Filippis, Elena A.; Roberts, Christine; Smoke, Christopher C.; Meyer, Christian; Højlund, Kurt; Yi, Zhengping; Mandarino, Lawrence J.

2010-01-01

OBJECTIVE Insulin resistance in skeletal muscle is an early phenomenon in the pathogenesis of type 2 diabetes. Studies of insulin resistance usually are highly focused. However, approaches that give a more global picture of abnormalities in insulin resistance are useful in pointing out new directions for research. In previous studies, gene expression analyses show a coordinated pattern of reduction in nuclear-encoded mitochondrial gene expression in insulin resistance. However, changes in mRNA levels may not predict changes in protein abundance. An approach to identify global protein abundance changes involving the use of proteomics was used here. RESEARCH DESIGN AND METHODS Muscle biopsies were obtained basally from lean, obese, and type 2 diabetic volunteers (n = 8 each); glucose clamps were used to assess insulin sensitivity. Muscle protein was subjected to mass spectrometry–based quantification using normalized spectral abundance factors. RESULTS Of 1,218 proteins assigned, 400 were present in at least half of all subjects. Of these, 92 were altered by a factor of 2 in insulin resistance, and of those, 15 were significantly increased or decreased by ANOVA (P < 0.05). Analysis of protein sets revealed patterns of decreased abundance in mitochondrial proteins and altered abundance of proteins involved with cytoskeletal structure (desmin and alpha actinin-2 both decreased), chaperone function (TCP-1 subunits increased), and proteasome subunits (increased). CONCLUSIONS The results confirm the reduction in mitochondrial proteins in insulin-resistant muscle and suggest that changes in muscle structure, protein degradation, and folding also characterize insulin resistance. PMID:19833877

Identification of transcriptome involved in atrazine detoxification and degradation in alfalfa (Medicago sativa) exposed to realistic environmental contamination.

PubMed

Zhang, Jing Jing; Lu, Yi Chen; Zhang, Shu Hao; Lu, Feng Fan; Yang, Hong

2016-08-01

Plants are constantly exposed to a variety of toxic compounds (or xenobiotics) such as pesticides (or herbicides). Atrazine (ATZ) as herbicide has become one of the environmental contaminants due to its intensive use during crop production. Plants have evolved strategies to cope with the adverse impact of ATZ. However, the mechanism for ATZ degradation and detoxification in plants is largely unknown. Here we employed a global RNA-sequencing (RNA-Seq) strategy to dissect transcriptome variation in alfalfa (Medicago sativa) exposed to ATZ. Four libraries were constructed including Root-ATZ (root control, ATZ-free), Shoot-ATZ, Root+ATZ (root treated with ATZ) and Shoot+ATZ. Hierarchical clustering was performed to display the expression patterns for all differentially expressed genes (DEGs) under ATZ exposure. Transcripts involved in ATZ detoxification, stress responses (e.g. oxidation and reduction, conjugation and hydrolytic reactions), and regulations of cysteine biosynthesis were identified. Several genes encoding glycosyltransferases, glutathione S-transferases or ABC transporters were up-regulated notably. Also, many other genes involved in oxidation-reduction, conjugation, and hydrolysis for herbicide degradation were differentially expressed. These results suggest that ATZ in alfalfa can be detoxified or degraded through different pathways. The expression patterns of some DEGs by high-throughput sequencing were well confirmed by qRT-PCR. Our results not only highlight the transcriptional complexity in alfalfa exposed to ATZ but represent a major improvement for analyzing transcriptional changes on a large scale as well. Copyright © 2016 Elsevier Inc. All rights reserved.

Metaproteomics reveals differential modes of metabolic coupling among ubiquitous oxygen minimum zone microbes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hawley, Alyse K.; Brewer, Heather M.; Norbeck, Angela D.

2014-08-05

Oxygen minimum zones (OMZs) are intrinsic water column features arising from respiratory oxygen demand during organic matter degradation in stratified marine waters. Currently OMZs are expanding due to global climate change. This expansion alters marine ecosystem function and the productivity of fisheries due to habitat compression and changes in biogeochemical cycling leading to fixed nitrogen loss and greenhouse gas production. Here we use metaproteomics to chart spatial and temporal patterns of gene expression along defined redox gradients in a seasonally anoxic fjord, Saanich Inlet to better understand microbial community responses to OMZ expansion. The expression of metabolic pathway components formore » nitrification, anaerobic ammonium oxidation (anammox), denitrification and inorganic carbon fixation predominantly co-varied with abundance and distribution patterns of Thaumarchaeota, Nitrospira, Planctomycetes and SUP05/ARCTIC96BD-19 Gammaproteobacteria. Within these groups, pathways mediating inorganic carbon fixation and nitrogen and sulfur transformations were differentially expressed across the redoxcline. Nitrification and inorganic carbon fixation pathways affiliated with Thaumarchaeota dominated dysoxic waters and denitrification, sulfur-oxidation and inorganic carbon fixation pathways affiliated with SUP05 dominated suboxic and anoxic waters. Nitrite-oxidation and anammox pathways affiliated with Nitrospina and Planctomycetes respectively, also exhibited redox partitioning between dysoxic and suboxic waters. The differential expression of these pathways under changing water column redox conditions has quantitative implications for coupled biogeochemical cycling linking different modes of inorganic carbon fixation with distributed nitrogen and sulfur-based energy metabolism extensible to coastal and open ocean OMZs.« less

Identifying spatially similar gene expression patterns in early stage fruit fly embryo images: binary feature versus invariant moment digital representations

PubMed Central

Gurunathan, Rajalakshmi; Van Emden, Bernard; Panchanathan, Sethuraman; Kumar, Sudhir

2004-01-01

Background Modern developmental biology relies heavily on the analysis of embryonic gene expression patterns. Investigators manually inspect hundreds or thousands of expression patterns to identify those that are spatially similar and to ultimately infer potential gene interactions. However, the rapid accumulation of gene expression pattern data over the last two decades, facilitated by high-throughput techniques, has produced a need for the development of efficient approaches for direct comparison of images, rather than their textual descriptions, to identify spatially similar expression patterns. Results The effectiveness of the Binary Feature Vector (BFV) and Invariant Moment Vector (IMV) based digital representations of the gene expression patterns in finding biologically meaningful patterns was compared for a small (226 images) and a large (1819 images) dataset. For each dataset, an ordered list of images, with respect to a query image, was generated to identify overlapping and similar gene expression patterns, in a manner comparable to what a developmental biologist might do. The results showed that the BFV representation consistently outperforms the IMV representation in finding biologically meaningful matches when spatial overlap of the gene expression pattern and the genes involved are considered. Furthermore, we explored the value of conducting image-content based searches in a dataset where individual expression components (or domains) of multi-domain expression patterns were also included separately. We found that this technique improves performance of both IMV and BFV based searches. Conclusions We conclude that the BFV representation consistently produces a more extensive and better list of biologically useful patterns than the IMV representation. The high quality of results obtained scales well as the search database becomes larger, which encourages efforts to build automated image query and retrieval systems for spatial gene expression patterns. PMID:15603586

Coupled local facilitation and global hydrologic inhibition drive landscape geometry in a patterned peatland

NASA Astrophysics Data System (ADS)

Acharya, S.; Kaplan, D. A.; Casey, S.; Cohen, M. J.; Jawitz, J. W.

2015-05-01

Self-organized landscape patterning can arise in response to multiple processes. Discriminating among alternative patterning mechanisms, particularly where experimental manipulations are untenable, requires process-based models. Previous modeling studies have attributed patterning in the Everglades (Florida, USA) to sediment redistribution and anisotropic soil hydraulic properties. In this work, we tested an alternate theory, the self-organizing-canal (SOC) hypothesis, by developing a cellular automata model that simulates pattern evolution via local positive feedbacks (i.e., facilitation) coupled with a global negative feedback based on hydrology. The model is forced by global hydroperiod that drives stochastic transitions between two patch types: ridge (higher elevation) and slough (lower elevation). We evaluated model performance using multiple criteria based on six statistical and geostatistical properties observed in reference portions of the Everglades landscape: patch density, patch anisotropy, semivariogram ranges, power-law scaling of ridge areas, perimeter area fractal dimension, and characteristic pattern wavelength. Model results showed strong statistical agreement with reference landscapes, but only when anisotropically acting local facilitation was coupled with hydrologic global feedback, for which several plausible mechanisms exist. Critically, the model correctly generated fractal landscapes that had no characteristic pattern wavelength, supporting the invocation of global rather than scale-specific negative feedbacks.

Coupled local facilitation and global hydrologic inhibition drive landscape geometry in a patterned peatland

NASA Astrophysics Data System (ADS)

Acharya, S.; Kaplan, D. A.; Casey, S.; Cohen, M. J.; Jawitz, J. W.

2015-01-01

Self-organized landscape patterning can arise in response to multiple processes. Discriminating among alternative patterning mechanisms, particularly where experimental manipulations are untenable, requires process-based models. Previous modeling studies have attributed patterning in the Everglades (Florida, USA) to sediment redistribution and anisotropic soil hydraulic properties. In this work, we tested an alternate theory, the self-organizing canal (SOC) hypothesis, by developing a cellular automata model that simulates pattern evolution via local positive feedbacks (i.e., facilitation) coupled with a global negative feedback based on hydrology. The model is forced by global hydroperiod that drives stochastic transitions between two patch types: ridge (higher elevation) and slough (lower elevation). We evaluated model performance using multiple criteria based on six statistical and geostatistical properties observed in reference portions of the Everglades landscape: patch density, patch anisotropy, semivariogram ranges, power-law scaling of ridge areas, perimeter area fractal dimension, and characteristic pattern wavelength. Model results showed strong statistical agreement with reference landscapes, but only when anisotropically acting local facilitation was coupled with hydrologic global feedback, for which several plausible mechanisms exist. Critically, the model correctly generated fractal landscapes that had no characteristic pattern wavelength, supporting the invocation of global rather than scale-specific negative feedbacks.

Global transcriptome analysis of the maize (Zea mays L.) inbred line 08LF during leaf senescence initiated by pollination-prevention.

PubMed

Wu, Liancheng; Li, Mingna; Tian, Lei; Wang, Shunxi; Wu, Liuji; Ku, Lixia; Zhang, Jun; Song, Xiaoheng; Liu, Haiping; Chen, Yanhui

2017-01-01

In maize (Zea mays), leaf senescence acts as a nutrient recycling process involved in proteins, lipids, and nucleic acids degradation and transport to the developing sink. However, the molecular mechanisms of pre-maturation associated with pollination-prevention remain unclear in maize. To explore global gene expression changes during the onset and progression of senescence in maize, the inbred line 08LF, with severe early senescence caused by pollination prevention, was selected. Phenotypic observation showed that the onset of leaf senescence of 08LF plants occurred approximately 14 days after silking (DAS) by pollination prevention. Transcriptional profiling analysis of the leaf at six developmental stages during induced senescence revealed that a total of 5,432 differentially expressed genes (DEGs) were identified, including 2314 up-regulated genes and 1925 down-regulated genes. Functional annotation showed that the up-regulated genes were mainly enriched in multi-organism process and nitrogen compound transport, whereas down-regulated genes were involved in photosynthesis. Expression patterns and pathway enrichment analyses of early-senescence related genes indicated that these DEGs are involved in complex regulatory networks, especially in the jasmonic acid pathway. In addition, transcription factors from several families were detected, particularly the CO-like, NAC, ERF, GRAS, WRKY and ZF-HD families, suggesting that these transcription factors might play important roles in driving leaf senescence in maize as a result of pollination-prevention.

RNA expression of genes involved in cytarabine metabolism and transport predicts cytarabine response in acute myeloid leukemia.

PubMed

Abraham, Ajay; Varatharajan, Savitha; Karathedath, Sreeja; Philip, Chepsy; Lakshmi, Kavitha M; Jayavelu, Ashok Kumar; Mohanan, Ezhilpavai; Janet, Nancy Beryl; Srivastava, Vivi M; Shaji, Ramachandran V; Zhang, Wei; Abraham, Aby; Viswabandya, Auro; George, Biju; Chandy, Mammen; Srivastava, Alok; Mathews, Vikram; Balasubramanian, Poonkuzhali

2015-07-01

Variation in terms of outcome and toxic side effects of treatment exists among acute myeloid leukemia (AML) patients on chemotherapy with cytarabine (Ara-C) and daunorubicin (Dnr). Candidate Ara-C metabolizing gene expression in primary AML cells is proposed to account for this variation. Ex vivo Ara-C sensitivity was determined in primary AML samples using MTT assay. mRNA expression of candidate Ara-C metabolizing genes were evaluated by RQPCR analysis. Global gene expression profiling was carried out for identifying differentially expressed genes between exvivo Ara-C sensitive and resistant samples. Wide interindividual variations in ex vivo Ara-C cytotoxicity were observed among samples from patients with AML and were stratified into sensitive, intermediately sensitive and resistant, based on IC50 values obtained by MTT assay. RNA expression of deoxycytidine kinase (DCK), human equilibrative nucleoside transporter-1 (ENT1) and ribonucleotide reductase M1 (RRM1) were significantly higher and cytidine deaminase (CDA) was significantly lower in ex vivo Ara-C sensitive samples. Higher DCK and RRM1 expression in AML patient's blast correlated with better DFS. Ara-C resistance index (RI), a mathematically derived quotient was proposed based on candidate gene expression pattern. Ara-C ex vivo sensitive samples were found to have significantly lower RI compared with resistant as well as samples from patients presenting with relapse. Patients with low RI supposedly highly sensitive to Ara-C were found to have higher incidence of induction death (p = 0.002; RR: 4.35 [95% CI: 1.69-11.22]). Global gene expression profiling undertaken to find out additional contributors of Ara-C resistance identified many apoptosis as well as metabolic pathway genes to be differentially expressed between Ara-C resistant and sensitive samples. This study highlights the importance of evaluating expression of candidate Ara-C metabolizing genes in predicting ex vivo drug response as well as treatment outcome. RI could be a predictor of ex vivo Ara-C response irrespective of cytogenetic and molecular risk groups and a potential biomarker for AML treatment outcome and toxicity. Original submitted 22 December 2014; Revision submitted 9 April 2015.

m-carboxycinnamic acid bishydroxamide improves developmental competence, reduces apoptosis and alters epigenetic status and gene expression pattern in cloned buffalo (Bubalus bubalis) embryos.

PubMed

Agrawal, H; Selokar, N L; Saini, M; Singh, M K; Chauhan, M S; Palta, P; Singla, S K; Manik, R S

2018-05-07

Incomplete or aberrant reprogramming of nuclear genome is one of the major problems in somatic cell nuclear transfer. In this study, we studied the effect of histone deacetylase inhibitor m-carboxycinnamic acid bishydroxamide (CBHA) on in vitro development of buffalo embryos produced by Hand-made cloning. Cloned embryos were treated with CBHA (0, 5, 10, 20 or 50 μM) for 10 hr from the start of reconstruction till activation. At 10 μM, but not at other concentrations examined, CBHA increased (p < .05) the blastocyst rate (63.77 ± 3.97% vs 48.63 ± 3.55%) and reduced (p < .05) the apoptotic index of the cloned blastocysts (8.91 ± 1.94 vs 4.36 ± 1.08) compared to untreated controls, to levels similar to those in IVF blastocysts (4.78 ± 0.74). CBHA treatment, at all the concentrations examined, increased (p < .05) the global level of H3K9ac in cloned blastocysts than in untreated controls to that observed in IVF blastocysts. Treatment with CBHA (10 μM) decreased (p < .05) the global level of H3K27me3 in cloned blastocysts than in untreated controls but it was still higher (p < .05) than in IVF blastocysts. CBHA (10 μM) treatment increased (p < .05) the relative expression level of pluripotency-related genes OCT-4 and NANOG, and anti-apoptotic gene BCL-XL, and decreased (p < .05) that of pro-apoptotic gene BAX than in untreated controls but did not affect the relative expression level of apoptosis-related genes p53 and CASPASE3 and epigenetics-related genes DNMT1, DNMT3a and HDAC1. These results suggest that treatment of cloned embryos with 10 μM CBHA improves the blastocyst rate, reduces the level of apoptosis and alters the epigenetic status and gene expression pattern. © 2018 Blackwell Verlag GmbH.

Identification of new developmentally regulated genes involved in Streptomyces coelicolor sporulation.

PubMed

Salerno, Paola; Persson, Jessica; Bucca, Giselda; Laing, Emma; Ausmees, Nora; Smith, Colin P; Flärdh, Klas

2013-12-05

The sporulation of aerial hyphae of Streptomyces coelicolor is a complex developmental process. Only a limited number of the genes involved in this intriguing morphological differentiation programme are known, including some key regulatory genes. The aim of this study was to expand our knowledge of the gene repertoire involved in S. coelicolor sporulation. We report a DNA microarray-based investigation of developmentally controlled gene expression in S. coelicolor. By comparing global transcription patterns of the wild-type parent and two mutants lacking key regulators of aerial hyphal sporulation, we found a total of 114 genes that had significantly different expression in at least one of the two mutants compared to the wild-type during sporulation. A whiA mutant showed the largest effects on gene expression, while only a few genes were specifically affected by whiH mutation. Seven new sporulation loci were investigated in more detail with respect to expression patterns and mutant phenotypes. These included SCO7449-7451 that affect spore pigment biogenesis; SCO1773-1774 that encode an L-alanine dehydrogenase and a regulator-like protein and are required for maturation of spores; SCO3857 that encodes a protein highly similar to a nosiheptide resistance regulator and affects spore maturation; and four additional loci (SCO4421, SCO4157, SCO0934, SCO1195) that show developmental regulation but no overt mutant phenotype. Furthermore, we describe a new promoter-probe vector that takes advantage of the red fluorescent protein mCherry as a reporter of cell type-specific promoter activity. Aerial hyphal sporulation in S. coelicolor is a technically challenging process for global transcriptomic investigations since it occurs only as a small fraction of the colony biomass and is not highly synchronized. Here we show that by comparing a wild-type to mutants lacking regulators that are specifically affecting processes in aerial hypha, it is possible to identify previously unknown genes with important roles in sporulation. The transcriptomic data reported here should also serve as a basis for identification of further developmentally important genes in future functional studies.

Rethinking pattern formation in reaction-diffusion systems

NASA Astrophysics Data System (ADS)

Halatek, J.; Frey, E.

2018-05-01

The present theoretical framework for the analysis of pattern formation in complex systems is mostly limited to the vicinity of fixed (global) equilibria. Here we present a new theoretical approach to characterize dynamical states arbitrarily far from (global) equilibrium. We show that reaction-diffusion systems that are driven by locally mass-conserving interactions can be understood in terms of local equilibria of diffusively coupled compartments. Diffusive coupling generically induces lateral redistribution of the globally conserved quantities, and the variable local amounts of these quantities determine the local equilibria in each compartment. We find that, even far from global equilibrium, the system is well characterized by its moving local equilibria. We apply this framework to in vitro Min protein pattern formation, a paradigmatic model for biological pattern formation. Within our framework we can predict and explain transitions between chemical turbulence and order arbitrarily far from global equilibrium. Our results reveal conceptually new principles of self-organized pattern formation that may well govern diverse dynamical systems.

Effects of Particulate Matter on Genomic DNA Methylation Content and iNOS Promoter Methylation

PubMed Central

Tarantini, Letizia; Bonzini, Matteo; Apostoli, Pietro; Pegoraro, Valeria; Bollati, Valentina; Marinelli, Barbara; Cantone, Laura; Rizzo, Giovanna; Hou, Lifang; Schwartz, Joel; Bertazzi, Pier Alberto; Baccarelli, Andrea

2009-01-01

Background Altered patterns of gene expression mediate the effects of particulate matter (PM) on human health, but mechanisms through which PM modifies gene expression are largely undetermined. Objectives We aimed at identifying short- and long-term effects of PM exposure on DNA methylation, a major genomic mechanism of gene expression control, in workers in an electric furnace steel plant with well-characterized exposure to PM with aerodynamic diameters < 10 μm (PM10). Methods We measured global genomic DNA methylation content estimated in Alu and long interspersed nuclear element-1 (LINE-1) repeated elements, and promoter DNA methylation of iNOS (inducible nitric oxide synthase), a gene suppressed by DNA methylation and induced by PM exposure in blood leukocytes. Quantitative DNA methylation analysis was performed through bisulfite PCR pyrosequencing on blood DNA obtained from 63 workers on the first day of a work week (baseline, after 2 days off work) and after 3 days of work (postexposure). Individual PM10 exposure was between 73.4 and 1,220 μg/m3. Results Global methylation content estimated in Alu and LINE-1 repeated elements did not show changes in postexposure measures compared with baseline. PM10 exposure levels were negatively associated with methylation in both Alu [β = −0.19 %5-methylcytosine (%5mC); p = 0.04] and LINE-1 [β = −0.34 %5mC; p = 0.04], likely reflecting long-term PM10 effects. iNOS promoter DNA methylation was significantly lower in postexposure blood samples compared with baseline (difference = −0.61 %5mC; p = 0.02). Conclusions We observed changes in global and gene specific methylation that should be further characterized in future investigations on the effects of PM. PMID:19270791

Global patterns of foliar nitrogen isotopes and their relationships with climate, mycorrhizal fungi, foliar nutrient concentrations, and nitrogen availability

Treesearch

Joseph M. Craine; Andrew J. Elmore; Marcos P. M. Aidar; Mercedes Bustamante; Todd E. Dawson; Erik A. Hobbie; Ansgar Kahmen; Michelle C. Mack; Kendra K. McLauchlan; Anders Michelsen; Gabriela Nardoto; Linda H. Pardo; Josep Penuelas; Peter B. Reich; Edward A.G. Schuur; William D. Stock; Pamela H. Templer; Ross A. Virginia; Jeffrey M. Welker; Ian J. Wright

2009-01-01

Ratios of nitrogen (N) isotopes in leaves could elucidate underlying patterns of N cycling across ecological gradients. To better understand global-scale patterns of N cycling, we compiled data on foliar N isotope ratios, foliar N concentrations, mycorrhizal type and climate for over 11 000 plants worldwide. Global-scale comparisons of other components of the N cycle...

Transcriptional Profiling of the Oral Pathogen Streptococcus mutans in Response to Competence Signaling Peptide XIP.

PubMed

Wenderska, Iwona B; Latos, Andrew; Pruitt, Benjamin; Palmer, Sara; Spatafora, Grace; Senadheera, Dilani B; Cvitkovitch, Dennis G

2017-01-01

In the cariogenic Streptococcus mutans , competence development is regulated by the ComRS signaling system comprised of the ComR regulator and the ComS prepeptide to the competence signaling peptide XIP (ComX-inducing peptide). Aside from competence development, XIP signaling has been demonstrated to regulate cell lysis, and recently, the expression of bacteriocins, small antimicrobial peptides used by bacteria to inhibit closely related species. Our study further explores the effect of XIP signaling on the S. mutans transcriptome. RNA sequencing revealed that XIP induction resulted in a global change in gene expression that was consistent with a stress response. An increase in several membrane-bound regulators, including HdrRM and BrsRM, involved in bacteriocin production, and the VicRKX system, involved in acid tolerance and biofilm formation, was observed. Furthermore, global changes in gene expression corresponded to changes observed during the stringent response to amino acid starvation. Effects were also observed on genes involved in sugar transport and carbon catabolite repression and included the levQRST and levDEFG operons. Finally, our work identified a novel heat shock-responsive intergenic region, encoding a small RNA, with a potential role in competence shutoff. IMPORTANCE Genetic competence provides bacteria with an opportunity to increase genetic diversity or acquire novel traits conferring a survival advantage. In the cariogenic pathogen Streptococcus mutans , DNA transformation is regulated by the competence stimulating peptide XIP (ComX-inducing peptide). The present study utilizes high-throughput RNA sequencing (RNAseq) to provide a greater understanding of how global gene expression patterns change in response to XIP. Overall, our work demonstrates that in S. mutans , XIP signaling induces a response that resembles the stringent response to amino acid starvation. We further identify a novel heat shock-responsive intergenic region with a potential role in competence shutoff. Together, our results provide further evidence that multiple stress response mechanisms are linked through the genetic competence signaling pathway in S. mutans .

Analysis of AtGUS1 and AtGUS2 in Arabidopsis root apex by a highly sensitive TSA-MISH method.

PubMed

Bruno, Leonardo; Ronchini, Matteo; Gagliardi, Olimpia; Corinti, Tamara; Chiappetta, Adriana; Gerola, Paolo; Bitonti, Maria B

2015-01-01

A new highly sensitive whole-mount in situ hybridization method, based on tyramide signal amplification (TSA-MISH) was developed and a combined GFP detection and TSA-MISH procedure was applied for the first time in plants, to precisely define the spatial pattern of AtGUS1 and AtGUS2 expression in the root apex. β-glucuronidases (GUSs) belonging to the glycosyl hydrolases (GHs) 79 family, are widely distributed in plants, but their functional role has not yet been fully investigated. In the model system Arabidopsis Thaliana, three different AtGUS genes have been identified which encode proteins with putative different fates. Endogenous GUS expression has been detected in different organs and tissues, but the cyto-histological domains of gene expression remain unclear. The results here reported show co-expression of AtGUS1 and AtGUS2 in different functional zones of the root apex (the cap central zone, the root cap meristem, the staminal cell niche and the cortical cell layers of the proximal meristem), while AtGUS2 is exclusively expressed in the cap peripheral layer and in the epidermis in the elongation zone. Interestingly, both genes are not expressed in the stelar portion of the proximal meristem. A spatial (cortex vs. stele) and temporal (proximal meristem vs. transition zone) regulation of AtGUS1 and AtGUS2 expression is therefore active in the root apex. This expression pattern, although globally consistent with the involvement of GUS activity in both cell proliferation and elongation, clearly indicates that AtGUS1 and AtGUS2 could control distinct downstream process depending on the developmental context and the interaction with other players of root growth control. In the future, the newly developed approaches may well be very useful to dissect such interactions.

Climate-soil Interactions: Global Change, Local Properties, and Ecological Sites

USDA-ARS?s Scientific Manuscript database

Global climate change is predicted to alter historic patterns of precipitation and temperature in rangelands globally. Vegetation community response to altered weather patterns will be mediated at the site level by local-scale properties that govern ecological potential, including geology, topograph...

Identification of biomarkers of radioresponse and subsequent progression towards lung cancer in normal human bronchial epithelial cells after HZE particle irradiation

NASA Astrophysics Data System (ADS)

Story, Michael; Ding, Liang-Hao; Park, Seongmi; Minna, John

Using variants of a non-oncogenically immortalized human bronchial epithelial cell line HBEC3-KT, we have examined global gene expression patterns after low and high LET irradiation up to 24h post-IR. Using supervised analyses we have identified 427 genes whoes expression can be used to discriminate the cellular response to γ-vs Si or Fe particles even when the biological outcome, cell death, is equivalent. Furthermore, genetic background also determines gene expression response. When HBEC3-KT is compared to the HBEC3-KT cells line where mutant k-RAS is over-expressed and p53 has been knocked down, HBEC-3KTr53, principal component analysis clearly shows that the response of each cell resides in a different 3-D space, that is, basal gene expression patterns as well as the gene expression response are unique to each cell type. Using regression analysis to examine these 427 genes show clusters of genes whose temporal expression patterns are the same and which are unique to a given radiation type. Ultimately, this approach will allow for the interrogation of gene promoters to identify response elements that drive how cells respond to different radiation types. We are extending our examination to O particles and are now examining gene expression as a function of beam quality. We have made substantial progress in the determination of cellular transformation by HZE particles for these cell lines. (Transformation as defined by the ability to grow in soft agar.) For HBEC-3KT, the spontaneous transformation frequency is about 10- 7.ExposuretoeitherF eorSiparticlesinc KT r53celllinedidnotshowanyincreaseintransf ormationf requencyaf terdosesof upto1Gy, however, thesp 3KT.W ehavenowisolatedover160individualf ocithatf ormedinsof tagarf romcellculturesthatwereirradia termcultureandthenre-introducedintosof tagartoassurethattheabilitytogrowinsof tagarisclonal.T odatew 30 With these cell isolates in hand we will begin to determine tumorigenicity by subcutaneous injections in nude mice. Tumors that develop will be examined for radiosensitivity and aggres-siveness and will be also be examined for genomic, epigenomic and proteomic changes. Com-parisons of unirradiated cells, transformed cells, and tumor cells will allow the development of biomarkers of radiation-induced lung cancer, in particular HZE-induced lung tumors, and help to generate risk factors for lung cancer as a result of travel through deep space environments.

Global-scale tectonic patterns on Pluto

NASA Astrophysics Data System (ADS)

Matsuyama, I.; Keane, J. T.; Kamata, S.

2016-12-01

The New Horizons spacecraft revealed a global-scale tectonic pattern on the surface of Pluto which is presumably related to its formation and early evolution. Changes in the rotational and tidal potentials, expansion, and loading can generate stresses capable of producing global-scale tectonic patterns. The current alignment of Sputnik Planum with the tidal axis suggests a reorientation of Pluto relative to the rotation and tidal axes, or true polar wander. This reorientation can be driven by mass loading associated with Sputnik Planum. We developed a general theoretical formalism for the calculation of tectonic patterns due to a variety of process including true polar wander, loading, and expansion. The formalism is general enough to be applicable to non-axisymmetric loads. We illustrate that the observed global-scale tectonic pattern can be explained by stresses generated by true polar wander, Sputnik Planum loading, and expansion.

Cancer cell redirection biomarker discovery using a mutual information approach.

PubMed

Roche, Kimberly; Feltus, F Alex; Park, Jang Pyo; Coissieux, Marie-May; Chang, Chenyan; Chan, Vera B S; Bentires-Alj, Mohamed; Booth, Brian W

2017-01-01

Introducing tumor-derived cells into normal mammary stem cell niches at a sufficiently high ratio of normal to tumorous cells causes those tumor cells to undergo a change to normal mammary phenotype and yield normal mammary progeny. This phenomenon has been termed cancer cell redirection. We have developed an in vitro model that mimics in vivo redirection of cancer cells by the normal mammary microenvironment. Using the RNA profiling data from this cellular model, we examined high-level characteristics of the normal, redirected, and tumor transcriptomes and found the global expression profiles clearly distinguish the three expression states. To identify potential redirection biomarkers that cause the redirected state to shift toward the normal expression pattern, we used mutual information relationships between normal, redirected, and tumor cell groups. Mutual information relationship analysis reduced a dataset of over 35,000 gene expression measurements spread over 13,000 curated gene sets to a set of 20 significant molecular signatures totaling 906 unique loci. Several of these molecular signatures are hallmark drivers of the tumor state. Using differential expression as a guide, we further refined the gene set to 120 core redirection biomarker genes. The expression levels of these core biomarkers are sufficient to make the normal and redirected gene expression states indistinguishable from each other but radically different from the tumor state.

Cancer cell redirection biomarker discovery using a mutual information approach

PubMed Central

Roche, Kimberly; Feltus, F. Alex; Park, Jang Pyo; Coissieux, Marie-May; Chang, Chenyan; Chan, Vera B. S.; Bentires-Alj, Mohamed

2017-01-01

Introducing tumor-derived cells into normal mammary stem cell niches at a sufficiently high ratio of normal to tumorous cells causes those tumor cells to undergo a change to normal mammary phenotype and yield normal mammary progeny. This phenomenon has been termed cancer cell redirection. We have developed an in vitro model that mimics in vivo redirection of cancer cells by the normal mammary microenvironment. Using the RNA profiling data from this cellular model, we examined high-level characteristics of the normal, redirected, and tumor transcriptomes and found the global expression profiles clearly distinguish the three expression states. To identify potential redirection biomarkers that cause the redirected state to shift toward the normal expression pattern, we used mutual information relationships between normal, redirected, and tumor cell groups. Mutual information relationship analysis reduced a dataset of over 35,000 gene expression measurements spread over 13,000 curated gene sets to a set of 20 significant molecular signatures totaling 906 unique loci. Several of these molecular signatures are hallmark drivers of the tumor state. Using differential expression as a guide, we further refined the gene set to 120 core redirection biomarker genes. The expression levels of these core biomarkers are sufficient to make the normal and redirected gene expression states indistinguishable from each other but radically different from the tumor state. PMID:28594912

Emergence of the self-similar property in gene expression dynamics

NASA Astrophysics Data System (ADS)

Ochiai, T.; Nacher, J. C.; Akutsu, T.

2007-08-01

Many theoretical models have recently been proposed to understand the structure of cellular systems composed of various types of elements (e.g., proteins, metabolites and genes) and their interactions. However, the cell is a highly dynamic system with thousands of functional elements fluctuating across temporal states. Therefore, structural analysis alone is not sufficient to reproduce the cell's observed behavior. In this article, we analyze the gene expression dynamics (i.e., how the amount of mRNA molecules in cell fluctuate in time) by using a new constructive approach, which reveals a symmetry embedded in gene expression fluctuations and characterizes the dynamical equation of gene expression (i.e., a specific stochastic differential equation). First, by using experimental data of human and yeast gene expression time series, we found a symmetry in short-time transition probability from time t to time t+1. We call it self-similarity symmetry (i.e., the gene expression short-time fluctuations contain a repeating pattern of smaller and smaller parts that are like the whole, but different in size). Secondly, we reconstruct the global behavior of the observed distribution of gene expression (i.e., scaling-law) and the local behavior of the power-law tail of this distribution. This approach may represent a step forward toward an integrated image of the basic elements of the whole cell.

RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis.

PubMed

Lichtinger, Monika; Ingram, Richard; Hannah, Rebecca; Müller, Dorothee; Clarke, Deborah; Assi, Salam A; Lie-A-Ling, Michael; Noailles, Laura; Vijayabaskar, M S; Wu, Mengchu; Tenen, Daniel G; Westhead, David R; Kouskoff, Valerie; Lacaud, Georges; Göttgens, Berthold; Bonifer, Constanze

2012-11-14

Cell fate decisions during haematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. To gain insight into how these transcription factors regulate the activation of haematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from haemogenic endothelium (HE) to haematopoietic progenitors. Using a Runx1-/- embryonic stem cell differentiation model expressing an inducible Runx1 gene, we show that in the absence of RUNX1, haematopoietic genes bind SCL/TAL1, FLI1 and C/EBPβ and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous de novo sites, initiating a local increase in histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of haematopoietic fate controlled by Runx1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing HE program but instead entails global reorganization of lineage-specific transcription factor assemblies.

RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis

PubMed Central

Lichtinger, Monika; Ingram, Richard; Hannah, Rebecca; Müller, Dorothee; Clarke, Deborah; Assi, Salam A; Lie-A-Ling, Michael; Noailles, Laura; Vijayabaskar, M S; Wu, Mengchu; Tenen, Daniel G; Westhead, David R; Kouskoff, Valerie; Lacaud, Georges; Göttgens, Berthold; Bonifer, Constanze

2012-01-01

Cell fate decisions during haematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. To gain insight into how these transcription factors regulate the activation of haematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from haemogenic endothelium (HE) to haematopoietic progenitors. Using a Runx1−/− embryonic stem cell differentiation model expressing an inducible Runx1 gene, we show that in the absence of RUNX1, haematopoietic genes bind SCL/TAL1, FLI1 and C/EBPβ and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous de novo sites, initiating a local increase in histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of haematopoietic fate controlled by Runx1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing HE program but instead entails global reorganization of lineage-specific transcription factor assemblies. PMID:23064151

Genome-Wide Association Study of Dietary Pattern Scores

PubMed Central

Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2017-01-01

Dietary patterns, representing global food supplies rather than specific nutrients or food intakes, have been associated with cardiovascular disease (CVD) incidence and mortality. The contribution of genetic factors in the determination of food intakes, preferences and dietary patterns has been previously established. The current study aimed to identify novel genetic factors associated with reported dietary pattern scores. Reported dietary patterns scores were derived from reported dietary intakes for the preceding month and were obtained through a food frequency questionnaire and genome-wide association study (GWAS) conducted in a study sample of 141 individuals. Reported Prudent and Western dietary patterns demonstrated nominal associations (p < 1 × 10−5) with 78 and 27 single nucleotide polymorphisms (SNPs), respectively. Among these, SNPs annotated to genes previously associated with neurological disorders, CVD risk factors and obesity were identified. Further assessment of SNPs demonstrated an impact on gene expression levels in blood for SNPs located within/near BCKDHB (p = 0.02) and the hypothalamic glucosensor PFKFB3 (p = 0.0004) genes, potentially mediated through an impact on the binding of transcription factors (TFs). Overrepresentations of glucose/energy homeostasis and hormone response TFs were also observed from SNP-surrounding sequences. Results from the current GWAS study suggest an interplay of genes involved in the metabolic response to dietary patterns on obesity, glucose metabolism and food-induced response in the brain in the adoption of dietary patterns. PMID:28644415

Buffalo embryos produced by handmade cloning from oocytes selected using brilliant cresyl blue staining have better developmental competence and quality and are closer to embryos produced by in vitro fertilization in terms of their epigenetic status and gene expression pattern.

PubMed

Mohapatra, Sushil K; Sandhu, Anjit; Neerukattu, Venkata S; Singh, Karn P; Selokar, Naresh L; Singla, Suresh K; Chauhan, Manmohan S; Manik, Radhey S; Palta, Prabhat

2015-04-01

We compared handmade cloned (HMC) buffalo blastocysts produced from oocytes stained with Brilliant Cresyl Blue (BCB) and classified into those with blue (BCB+) or colorless cytoplasm (BCB-). The blastocyst rate was higher (p<0.001) for BCB+ than for BCB- oocytes (43.41 ± 2.54 vs. 22.74 ± 1.76%). BCB+ blastocysts had inner cell mass (ICM) cell number, ICM-to-trophectoderm ratio, global level of H3K18ac, apoptotic index, and expression level of BCL-XL, but not that of CASPASE-3, similar to that of blastocysts produced through in vitro fertilization (IVF), which was higher (p<0.05) than that of BCB- blastocysts. The global level of H3K9me2, which was similar in BCB+ and BCB- blastocysts, was higher (p<0.01) than that in IVF blastocysts. The expression level of OCT4 and SOX2 was higher (p<0.05) and that of GATA2 was lower (p<0.05) in BCB+ than that in BCB- blastocysts, whereas that of DNMT1, DNMT3a, NANOG, and CDX2 was not significantly different between the two groups. The expression level of DNMT1, OCT4, NANOG, and SOX2 was lower (p<0.05) and that of CDX2 was higher (p<0.05) in BCB+ than in IVF blastocysts. In conclusion, because BCB+ blastocysts have better developmental competence and are closer to IVF blastocysts in terms of quality, epigenetic status, and gene expression than BCB- blastocysts, BCB staining can be used effectively for selection of developmentally competent oocytes for HMC.

Global Expression Profiling of Globose Basal Cells and Neurogenic Progression Within the Olfactory Epithelium

PubMed Central

Krolewski, Richard C.; Packard, Adam; Schwob, James E.

2013-01-01

Ongoing, lifelong neurogenesis maintains the neuronal population of the olfactory epithelium in the face of piecemeal neuronal turnover and restores it following wholesale loss. The molecular phenotypes corresponding to different stages along the progression from multipotent globose basal cell (GBC) progenitor to differentiated olfactory sensory neuron are poorly characterized. We used the transgenic expression of enhanced green fluorescent protein (eGFP) and cell surface markers to FACS-isolate ΔSox2-eGFP(+) GBCs, Neurog1-eGFP(+) GBCs and immature neurons, and ΔOMP-eGFP(+) mature neurons from normal adult mice. In addition, the latter two populations were also collected 3 weeks after olfactory bulb ablation, a lesion that results in persistently elevated neurogenesis. Global profiling of mRNA from the populations indicates that all stages of neurogenesis share a cohort of >2,100 genes that are upregulated compared to sustentacular cells. A further cohort of >1,200 genes are specifically upregulated in GBCs as compared to sustentacular cells and differentiated neurons. The increased rate of neurogenesis caused by olfactory bulbectomy had little effect on the transcriptional profile of the Neurog1-eGFP(+) population. In contrast, the abbreviated lifespan of ΔOMP-eGFP(+) neurons born in the absence of the bulb correlated with substantial differences in gene expression as compared to the mature neurons of the normal epithelium. Detailed examination of the specific genes upregulated in the different progenitor populations revealed that the chromatin modifying complex proteins LSD1 and coREST were expressed sequentially in upstream ΔSox2-eGFP(+) GBCs and Neurog1-eGFP(+) GBCs/immature neurons. The expression patterns of these proteins are dynamically regulated after activation of the epithelium by methyl bromide lesion. PMID:22847514

Buffalo Embryos Produced by Handmade Cloning from Oocytes Selected Using Brilliant Cresyl Blue Staining Have Better Developmental Competence and Quality and Are Closer to Embryos Produced by In Vitro Fertilization in Terms of Their Epigenetic Status and Gene Expression Pattern

PubMed Central

Mohapatra, Sushil K.; Sandhu, Anjit; Neerukattu, Venkata S.; Singh, Karn P.; Selokar, Naresh L.; Singla, Suresh K.; Chauhan, Manmohan S.; Manik, Radhey S.

2015-01-01

Abstract We compared handmade cloned (HMC) buffalo blastocysts produced from oocytes stained with Brilliant Cresyl Blue (BCB) and classified into those with blue (BCB+) or colorless cytoplasm (BCB−). The blastocyst rate was higher (p<0.001) for BCB+ than for BCB− oocytes (43.41±2.54 vs. 22.74±1.76%). BCB+ blastocysts had inner cell mass (ICM) cell number, ICM-to-trophectoderm ratio, global level of H3K18ac, apoptotic index, and expression level of BCL-XL, but not that of CASPASE-3, similar to that of blastocysts produced through in vitro fertilization (IVF), which was higher (p<0.05) than that of BCB− blastocysts. The global level of H3K9me2, which was similar in BCB+ and BCB− blastocysts, was higher (p<0.01) than that in IVF blastocysts. The expression level of OCT4 and SOX2 was higher (p<0.05) and that of GATA2 was lower (p<0.05) in BCB+ than that in BCB− blastocysts, whereas that of DNMT1, DNMT3a, NANOG, and CDX2 was not significantly different between the two groups. The expression level of DNMT1, OCT4, NANOG, and SOX2 was lower (p<0.05) and that of CDX2 was higher (p<0.05) in BCB+ than in IVF blastocysts. In conclusion, because BCB+ blastocysts have better developmental competence and are closer to IVF blastocysts in terms of quality, epigenetic status, and gene expression than BCB− blastocysts, BCB staining can be used effectively for selection of developmentally competent oocytes for HMC. PMID:25826727

Non-canonical TAF complexes regulate active promoters in human embryonic stem cells

PubMed Central

Maston, Glenn A; Zhu, Lihua Julie; Chamberlain, Lynn; Lin, Ling; Fang, Minggang; Green, Michael R

2012-01-01

The general transcription factor TFIID comprises the TATA-box-binding protein (TBP) and approximately 14 TBP-associated factors (TAFs). Here we find, unexpectedly, that undifferentiated human embryonic stem cells (hESCs) contain only six TAFs (TAFs 2, 3, 5, 6, 7 and 11), whereas following differentiation all TAFs are expressed. Directed and global chromatin immunoprecipitation analyses reveal an unprecedented promoter occupancy pattern: most active genes are bound by only TAFs 3 and 5 along with TBP, whereas the remaining active genes are bound by TBP and all six hESC TAFs. Consistent with these results, hESCs contain a previously undescribed complex comprising TAFs 2, 6, 7, 11 and TBP. Altering the composition of hESC TAFs, either by depleting TAFs that are present or ectopically expressing TAFs that are absent, results in misregulated expression of pluripotency genes and induction of differentiation. Thus, the selective expression and use of TAFs underlies the ability of hESCs to self-renew. DOI: http://dx.doi.org/10.7554/eLife.00068.001 PMID:23150797

Global marine bacterial diversity peaks at high latitudes in winter

PubMed Central

Ladau, Joshua; Sharpton, Thomas J; Finucane, Mariel M; Jospin, Guillaume; Kembel, Steven W; O'Dwyer, James; Koeppel, Alexander F; Green, Jessica L; Pollard, Katherine S

2013-01-01

Genomic approaches to characterizing bacterial communities are revealing significant differences in diversity and composition between environments. But bacterial distributions have not been mapped at a global scale. Although current community surveys are way too sparse to map global diversity patterns directly, there is now sufficient data to fit accurate models of how bacterial distributions vary across different environments and to make global scale maps from these models. We apply this approach to map the global distributions of bacteria in marine surface waters. Our spatially and temporally explicit predictions suggest that bacterial diversity peaks in temperate latitudes across the world's oceans. These global peaks are seasonal, occurring 6 months apart in the two hemispheres, in the boreal and austral winters. This pattern is quite different from the tropical, seasonally consistent diversity patterns observed for most macroorganisms. However, like other marine organisms, surface water bacteria are particularly diverse in regions of high human environmental impacts on the oceans. Our maps provide the first picture of bacterial distributions at a global scale and suggest important differences between the diversity patterns of bacteria compared with other organisms. PMID:23514781

Transcriptome analysis at four developmental stages of grape berry (Vitis vinifera cv. Shiraz) provides insights into regulated and coordinated gene expression

PubMed Central

2012-01-01

Background Vitis vinifera berry development is characterised by an initial phase where the fruit is small, hard and acidic, followed by a lag phase known as veraison. In the final phase, berries become larger, softer and sweeter and accumulate an array of organoleptic compounds. Since the physiological and biochemical makeup of grape berries at harvest has a profound impact on the characteristics of wine, there is great interest in characterising the molecular and biophysical changes that occur from flowering through veraison and ripening, including the coordination and temporal regulation of metabolic gene pathways. Advances in deep-sequencing technologies, combined with the availability of increasingly accurate V. vinifera genomic and transcriptomic data, have enabled us to carry out RNA-transcript expression analysis on a global scale at key points during berry development. Results A total of 162 million 100-base pair reads were generated from pooled Vitis vinifera (cv. Shiraz) berries sampled at 3-weeks post-anthesis, 10- and 11-weeks post-anthesis (corresponding to early and late veraison) and at 17-weeks post-anthesis (harvest). Mapping reads from each developmental stage (36-45 million) onto the NCBI RefSeq transcriptome of 23,720 V. vinifera mRNAs revealed that at least 75% of these transcripts were detected in each sample. RNA-Seq analysis uncovered 4,185 transcripts that were significantly upregulated at a single developmental stage, including 161 transcription factors. Clustering transcripts according to distinct patterns of transcription revealed coordination in metabolic pathways such as organic acid, stilbene and terpenoid metabolism. From the phenylpropanoid/stilbene biosynthetic pathway at least 46 transcripts were upregulated in ripe berries when compared to veraison and immature berries, and 12 terpene synthases were predominantly detected only in a single sample. Quantitative real-time PCR was used to validate the expression pattern of 12 differentially expressed genes from primary and secondary metabolic pathways. Conclusions In this study we report the global transcriptional profile of Shiraz grapes at key stages of development. We have undertaken a comprehensive analysis of gene families contributing to commercially important berry characteristics and present examples of co-regulation and differential gene expression. The data reported here will provide an invaluable resource for the on-going molecular investigation of wine grapes. PMID:23227855

Comprehensive evaluation of AmpliSeq transcriptome, a novel targeted whole transcriptome RNA sequencing methodology for global gene expression analysis.

PubMed

Li, Wenli; Turner, Amy; Aggarwal, Praful; Matter, Andrea; Storvick, Erin; Arnett, Donna K; Broeckel, Ulrich

2015-12-16

Whole transcriptome sequencing (RNA-seq) represents a powerful approach for whole transcriptome gene expression analysis. However, RNA-seq carries a few limitations, e.g., the requirement of a significant amount of input RNA and complications led by non-specific mapping of short reads. The Ion AmpliSeq Transcriptome Human Gene Expression Kit (AmpliSeq) was recently introduced by Life Technologies as a whole-transcriptome, targeted gene quantification kit to overcome these limitations of RNA-seq. To assess the performance of this new methodology, we performed a comprehensive comparison of AmpliSeq with RNA-seq using two well-established next-generation sequencing platforms (Illumina HiSeq and Ion Torrent Proton). We analyzed standard reference RNA samples and RNA samples obtained from human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). Using published data from two standard RNA reference samples, we observed a strong concordance of log2 fold change for all genes when comparing AmpliSeq to Illumina HiSeq (Pearson's r = 0.92) and Ion Torrent Proton (Pearson's r = 0.92). We used ROC, Matthew's correlation coefficient and RMSD to determine the overall performance characteristics. All three statistical methods demonstrate AmpliSeq as a highly accurate method for differential gene expression analysis. Additionally, for genes with high abundance, AmpliSeq outperforms the two RNA-seq methods. When analyzing four closely related hiPSC-CM lines, we show that both AmpliSeq and RNA-seq capture similar global gene expression patterns consistent with known sources of variations. Our study indicates that AmpliSeq excels in the limiting areas of RNA-seq for gene expression quantification analysis. Thus, AmpliSeq stands as a very sensitive and cost-effective approach for very large scale gene expression analysis and mRNA marker screening with high accuracy.

Defining Global Gene Expression Changes of the Hypothalamic-Pituitary-Gonadal Axis in Female sGnRH-Antisense Transgenic Common Carp (Cyprinus carpio)

PubMed Central

Xu, Jing; Huang, Wei; Zhong, Chengrong; Luo, Daji; Li, Shuangfei; Zhu, Zuoyan; Hu, Wei

2011-01-01

Background The hypothalamic-pituitary-gonadal (HPG) axis is critical in the development and regulation of reproduction in fish. The inhibition of neuropeptide gonadotropin-releasing hormone (GnRH) expression may diminish or severely hamper gonadal development due to it being the key regulator of the axis, and then provide a model for the comprehensive study of the expression patterns of genes with respect to the fish reproductive system. Methodology/Principal Findings In a previous study we injected 342 fertilized eggs from the common carp (Cyprinus carpio) with a gene construct that expressed antisense sGnRH. Four years later, we found a total of 38 transgenic fish with abnormal or missing gonads. From this group we selected the 12 sterile females with abnormal ovaries in which we combined suppression subtractive hybridization (SSH) and cDNA microarray analysis to define changes in gene expression of the HPG axis in the present study. As a result, nine, 28, and 212 genes were separately identified as being differentially expressed in hypothalamus, pituitary, and ovary, of which 87 genes were novel. The number of down- and up-regulated genes was five and four (hypothalamus), 16 and 12 (pituitary), 119 and 93 (ovary), respectively. Functional analyses showed that these genes involved in several biological processes, such as biosynthesis, organogenesis, metabolism pathways, immune systems, transport links, and apoptosis. Within these categories, significant genes for neuropeptides, gonadotropins, metabolic, oogenesis and inflammatory factors were identified. Conclusions/Significance This study indicated the progressive scaling-up effect of hypothalamic sGnRH antisense on the pituitary and ovary receptors of female carp and provided comprehensive data with respect to global changes in gene expression throughout the HPG signaling pathway, contributing towards improving our understanding of the molecular mechanisms and regulative pathways in the reproductive system of teleost fish. PMID:21695218

Convergence of soil nitrogen isotopes across global climate gradients

USGS Publications Warehouse

Craine, Joseph M.; Elmore, Andrew J.; Wang, Lixin; Augusto, Laurent; Baisden, W. Troy; Brookshire, E. N. J.; Cramer, Michael D.; Hasselquist, Niles J.; Hobbie, Erik A.; Kahmen, Ansgar; Koba, Keisuke; Kranabetter, J. Marty; Mack, Michelle C.; Marin-Spiotta, Erika; Mayor, Jordan R.; McLauchlan, Kendra K.; Michelsen, Anders; Nardoto, Gabriela B.; Oliveira, Rafael S.; Perakis, Steven S.; Peri, Pablo L.; Quesada, Carlos A.; Richter, Andreas; Schipper, Louis A.; Stevenson, Bryan A.; Turner, Benjamin L.; Viani, Ricardo A. G.; Wanek, Wolfgang; Zeller, Bernd

2015-01-01

Quantifying global patterns of terrestrial nitrogen (N) cycling is central to predicting future patterns of primary productivity, carbon sequestration, nutrient fluxes to aquatic systems, and climate forcing. With limited direct measures of soil N cycling at the global scale, syntheses of the 15 N: 14 N ratio of soil organic matter across climate gradients provide key insights into understanding global patterns of N cycling. In synthesizing data from over 6000 soil samples, we show strong global relationships among soil N isotopes, mean annual temperature (MAT), mean annual precipitation (MAP), and the concentrations of organic carbon and clay in soil. In both hot ecosystems and dry ecosystems, soil organic matter was more enriched in 15 N than in corresponding cold ecosystems or wet ecosystems. Below a MAT of 9.8°C, soil δ15N was invariant with MAT. At the global scale, soil organic C concentrations also declined with increasing MAT and decreasing MAP. After standardizing for variation among mineral soils in soil C and clay concentrations, soil δ15N showed no consistent trends across global climate and latitudinal gradients. Our analyses could place new constraints on interpretations of patterns of ecosystem N cycling and global budgets of gaseous N loss.

Convergence of soil nitrogen isotopes across global climate gradients.

PubMed

Craine, Joseph M; Elmore, Andrew J; Wang, Lixin; Augusto, Laurent; Baisden, W Troy; Brookshire, E N J; Cramer, Michael D; Hasselquist, Niles J; Hobbie, Erik A; Kahmen, Ansgar; Koba, Keisuke; Kranabetter, J Marty; Mack, Michelle C; Marin-Spiotta, Erika; Mayor, Jordan R; McLauchlan, Kendra K; Michelsen, Anders; Nardoto, Gabriela B; Oliveira, Rafael S; Perakis, Steven S; Peri, Pablo L; Quesada, Carlos A; Richter, Andreas; Schipper, Louis A; Stevenson, Bryan A; Turner, Benjamin L; Viani, Ricardo A G; Wanek, Wolfgang; Zeller, Bernd

2015-02-06

Quantifying global patterns of terrestrial nitrogen (N) cycling is central to predicting future patterns of primary productivity, carbon sequestration, nutrient fluxes to aquatic systems, and climate forcing. With limited direct measures of soil N cycling at the global scale, syntheses of the (15)N:(14)N ratio of soil organic matter across climate gradients provide key insights into understanding global patterns of N cycling. In synthesizing data from over 6000 soil samples, we show strong global relationships among soil N isotopes, mean annual temperature (MAT), mean annual precipitation (MAP), and the concentrations of organic carbon and clay in soil. In both hot ecosystems and dry ecosystems, soil organic matter was more enriched in (15)N than in corresponding cold ecosystems or wet ecosystems. Below a MAT of 9.8°C, soil δ(15)N was invariant with MAT. At the global scale, soil organic C concentrations also declined with increasing MAT and decreasing MAP. After standardizing for variation among mineral soils in soil C and clay concentrations, soil δ(15)N showed no consistent trends across global climate and latitudinal gradients. Our analyses could place new constraints on interpretations of patterns of ecosystem N cycling and global budgets of gaseous N loss.

Early Developmental and Evolutionary Origins of Gene Body DNA Methylation Patterns in Mammalian Placentas

PubMed Central

Schroeder, Diane I.; Jayashankar, Kartika; Douglas, Kory C.; Thirkill, Twanda L.; York, Daniel; Dickinson, Pete J.; Williams, Lawrence E.; Samollow, Paul B.; Ross, Pablo J.; Bannasch, Danika L.; Douglas, Gordon C.; LaSalle, Janine M.

2015-01-01

Over the last 20-80 million years the mammalian placenta has taken on a variety of morphologies through both divergent and convergent evolution. Recently we have shown that the human placenta genome has a unique epigenetic pattern of large partially methylated domains (PMDs) and highly methylated domains (HMDs) with gene body DNA methylation positively correlating with level of gene expression. In order to determine the evolutionary conservation of DNA methylation patterns and transcriptional regulatory programs in the placenta, we performed a genome-wide methylome (MethylC-seq) analysis of human, rhesus macaque, squirrel monkey, mouse, dog, horse, and cow placentas as well as opossum extraembryonic membrane. We found that, similar to human placenta, mammalian placentas and opossum extraembryonic membrane have globally lower levels of methylation compared to somatic tissues. Higher relative gene body methylation was the conserved feature across all mammalian placentas, despite differences in PMD/HMDs and absolute methylation levels. Specifically, higher methylation over the bodies of genes involved in mitosis, vesicle-mediated transport, protein phosphorylation, and chromatin modification was observed compared with the rest of the genome. As in human placenta, higher methylation is associated with higher gene expression and is predictive of genic location across species. Analysis of DNA methylation in oocytes and preimplantation embryos shows a conserved pattern of gene body methylation similar to the placenta. Intriguingly, mouse and cow oocytes and mouse early embryos have PMD/HMDs but their placentas do not, suggesting that PMD/HMDs are a feature of early preimplantation methylation patterns that become lost during placental development in some species and following implantation of the embryo. PMID:26241857

Distinct polyadenylation landscapes of diverse human tissues revealed by a modified PA-seq strategy

PubMed Central

2013-01-01

Background Polyadenylation is a key regulatory step in eukaryotic gene expression and one of the major contributors of transcriptome diversity. Aberrant polyadenylation often associates with expression defects and leads to human diseases. Results To better understand global polyadenylation regulation, we have developed a polyadenylation sequencing (PA-seq) approach. By profiling polyadenylation events in 13 human tissues, we found that alternative cleavage and polyadenylation (APA) is prevalent in both protein-coding and noncoding genes. In addition, APA usage, similar to gene expression profiling, exhibits tissue-specific signatures and is sufficient for determining tissue origin. A 3′ untranslated region shortening index (USI) was further developed for genes with tandem APA sites. Strikingly, the results showed that different tissues exhibit distinct patterns of shortening and/or lengthening of 3′ untranslated regions, suggesting the intimate involvement of APA in establishing tissue or cell identity. Conclusions This study provides a comprehensive resource to uncover regulated polyadenylation events in human tissues and to characterize the underlying regulatory mechanism. PMID:24025092

Annotation of gene function in citrus using gene expression information and co-expression networks

PubMed Central

2014-01-01

Background The genus Citrus encompasses major cultivated plants such as sweet orange, mandarin, lemon and grapefruit, among the world’s most economically important fruit crops. With increasing volumes of transcriptomics data available for these species, Gene Co-expression Network (GCN) analysis is a viable option for predicting gene function at a genome-wide scale. GCN analysis is based on a “guilt-by-association” principle whereby genes encoding proteins involved in similar and/or related biological processes may exhibit similar expression patterns across diverse sets of experimental conditions. While bioinformatics resources such as GCN analysis are widely available for efficient gene function prediction in model plant species including Arabidopsis, soybean and rice, in citrus these tools are not yet developed. Results We have constructed a comprehensive GCN for citrus inferred from 297 publicly available Affymetrix Genechip Citrus Genome microarray datasets, providing gene co-expression relationships at a genome-wide scale (33,000 transcripts). The comprehensive citrus GCN consists of a global GCN (condition-independent) and four condition-dependent GCNs that survey the sweet orange species only, all citrus fruit tissues, all citrus leaf tissues, or stress-exposed plants. All of these GCNs are clustered using genome-wide, gene-centric (guide) and graph clustering algorithms for flexibility of gene function prediction. For each putative cluster, gene ontology (GO) enrichment and gene expression specificity analyses were performed to enhance gene function, expression and regulation pattern prediction. The guide-gene approach was used to infer novel roles of genes involved in disease susceptibility and vitamin C metabolism, and graph-clustering approaches were used to investigate isoprenoid/phenylpropanoid metabolism in citrus peel, and citric acid catabolism via the GABA shunt in citrus fruit. Conclusions Integration of citrus gene co-expression networks, functional enrichment analysis and gene expression information provide opportunities to infer gene function in citrus. We present a publicly accessible tool, Network Inference for Citrus Co-Expression (NICCE, http://citrus.adelaide.edu.au/nicce/home.aspx), for the gene co-expression analysis in citrus. PMID:25023870

Drosophila segmentation: supercomputer simulation of prepattern hierarchy.

PubMed

Hunding, A; Kauffman, S A; Goodwin, B C

1990-08-09

Spontaneous prepattern formation in a two level hierarchy of reaction-diffusion systems is simulated in three space co-ordinates and time, mimicking gap gene and primary pair-rule gene expression. The model rests on the idea of Turing systems of the second kind, in which one prepattern generates position dependent rate constants for a subsequent reaction-diffusion system. Maternal genes are assumed responsible for setting up gradients from the anterior and posterior ends, one of which is needed to stabilize a double period prepattern suggested to underly the read out of the gap genes. The resulting double period pattern in turn stabilizes the next prepattern in the hierarchy, which has a short wavelength with many characteristics of the stripes seen in actual primary pair-rule gene expression. Without such hierarchical stabilization, reaction-diffusion mechanisms yield highly patchy short wave length patterns, and thus unreliable stripes. The model yields seven stable stripes located in the middle of the embryo, with the potential for additional expression near the poles, as observed experimentally. The model does not rely on specific chemical reaction kinetics, rather the effect is general to many such kinetic schemes. This makes it robust to parameter changes, and it has good potential for adapting to size and shape changes as well. The study thus suggests that the crucial organizing principle in early Drosophila embryogenesis is based on global field mechanisms, not on particular local interactions.

Genome-wide Mapping Reveals Conservation of Promoter DNA Methylation Following Chicken Domestication

PubMed Central

Li, Qinghe; Wang, Yuanyuan; Hu, Xiaoxiang; Zhao, Yaofeng; Li, Ning

2015-01-01

It is well-known that environment influences DNA methylation, however, the extent of heritable DNA methylation variation following animal domestication remains largely unknown. Using meDIP-chip we mapped the promoter methylomes for 23,316 genes in muscle tissues of ancestral and domestic chickens. We systematically examined the variation of promoter DNA methylation in terms of different breeds, differentially expressed genes, SNPs and genes undergo genetic selection sweeps. While considerable changes in DNA sequence and gene expression programs were prevalent, we found that the inter-strain DNA methylation patterns were highly conserved in promoter region between the wild and domestic chicken breeds. Our data suggests a global preservation of DNA methylation between the wild and domestic chicken breeds in either a genome-wide or locus-specific scale in chick muscle tissues. PMID:25735894

Quantitative Proteomics Reveals Fundamental Regulatory Differences in Oncogenic HRAS and Isocitrate Dehydrogenase (IDH1) Driven Astrocytoma.

PubMed

Doll, Sophia; Urisman, Anatoly; Oses-Prieto, Juan A; Arnott, David; Burlingame, Alma L

2017-01-01

Glioblastoma multiformes (GBMs) are high-grade astrocytomas and the most common brain malignancies. Primary GBMs are often associated with disturbed RAS signaling, and expression of oncogenic HRAS results in a malignant phenotype in glioma cell lines. Secondary GBMs arise from lower-grade astrocytomas, have slower progression than primary tumors, and contain IDH1 mutations in over 70% of cases. Despite significant amount of accumulating genomic and transcriptomic data, the fundamental mechanistic differences of gliomagenesis in these two types of high-grade astrocytoma remain poorly understood. Only a few studies have attempted to investigate the proteome, phosphorylation signaling, and epigenetic regulation in astrocytoma. In the present study, we applied quantitative phosphoproteomics to identify the main signaling differences between oncogenic HRAS and mutant IDH1-driven glioma cells as models of primary and secondary GBM, respectively. Our analysis confirms the driving roles of the MAPK and PI3K/mTOR signaling pathways in HRAS driven cells and additionally uncovers dysregulation of other signaling pathways. Although a subset of the signaling changes mediated by HRAS could be reversed by a MEK inhibitor, dual inhibition of MEK and PI3K resulted in more complete reversal of the phosphorylation patterns produced by HRAS expression. In contrast, cells expressing mutant IDH1 did not show significant activation of MAPK or PI3K/mTOR pathways. Instead, global downregulation of protein expression was observed. Targeted proteomic analysis of histone modifications identified significant histone methylation, acetylation, and butyrylation changes in the mutant IDH1 expressing cells, consistent with a global transcriptional repressive state. Our findings offer novel mechanistic insight linking mutant IDH1 associated inhibition of histone demethylases with specific histone modification changes to produce global transcriptional repression in secondary glioblastoma. Our proteomic datasets are available for download and provide a comprehensive catalogue of alterations in protein abundance, phosphorylation, and histone modifications in oncogenic HRAS and IDH1 driven astrocytoma cells beyond the transcriptomic level. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Explaining patterns in the ratification of global environmental treaties

NASA Technical Reports Server (NTRS)

Cook, David W.

1991-01-01

A study was made of the ratification behavior of 160 countries with respect to 38 global environmental treaties. The study identifies and explains patterns in the ratification of treaties, providing two means of assessing the likelihood that any given country will support global environmental treaties. National ratification totals reveal a pattern of high ratification by countries in Western Europe, North America, Japan, Australia, and New Zealand. A country's standing within the range of high to low ratification rates can be explained by the statistical model developed in the study. This research allows one to identify countries likely to support global environmental treaties.

Global linkages between teleconnection patterns and the terrestrial biosphere

NASA Astrophysics Data System (ADS)

Dahlin, Kyla M.; Ault, Toby R.

2018-07-01

Interannual variability in the global carbon cycle is largely due to variations in carbon uptake by terrestrial ecosystems, yet linkages between climate variability and variability in the terrestrial carbon cycle are not well understood at the global scale. Using a 30-year satellite record of semi-monthly leaf area index (LAI), we show that four modes of climate variability - El Niño/Southern Oscillation, the North Atlantic Oscillation, the Atlantic Meridional Mode, and the Indian Ocean Dipole Mode - strongly impact interannual vegetation growth patterns, with 68% of the land surface impacted by at least one of these teleconnection patterns, yet the spatial distribution of these impacts is heterogeneous. Considering the patterns' impacts by biome, none has an exclusively positive or negative relationship with LAI. Our findings imply that future changes in the frequency and/or magnitude of teleconnection patterns will lead to diverse changes to the terrestrial biosphere and the global carbon cycle.

Multivariate Pattern Classification of Facial Expressions Based on Large-Scale Functional Connectivity.

PubMed

Liang, Yin; Liu, Baolin; Li, Xianglin; Wang, Peiyuan

2018-01-01

It is an important question how human beings achieve efficient recognition of others' facial expressions in cognitive neuroscience, and it has been identified that specific cortical regions show preferential activation to facial expressions in previous studies. However, the potential contributions of the connectivity patterns in the processing of facial expressions remained unclear. The present functional magnetic resonance imaging (fMRI) study explored whether facial expressions could be decoded from the functional connectivity (FC) patterns using multivariate pattern analysis combined with machine learning algorithms (fcMVPA). We employed a block design experiment and collected neural activities while participants viewed facial expressions of six basic emotions (anger, disgust, fear, joy, sadness, and surprise). Both static and dynamic expression stimuli were included in our study. A behavioral experiment after scanning confirmed the validity of the facial stimuli presented during the fMRI experiment with classification accuracies and emotional intensities. We obtained whole-brain FC patterns for each facial expression and found that both static and dynamic facial expressions could be successfully decoded from the FC patterns. Moreover, we identified the expression-discriminative networks for the static and dynamic facial expressions, which span beyond the conventional face-selective areas. Overall, these results reveal that large-scale FC patterns may also contain rich expression information to accurately decode facial expressions, suggesting a novel mechanism, which includes general interactions between distributed brain regions, and that contributes to the human facial expression recognition.

Multivariate Pattern Classification of Facial Expressions Based on Large-Scale Functional Connectivity

PubMed Central

Liang, Yin; Liu, Baolin; Li, Xianglin; Wang, Peiyuan

2018-01-01

It is an important question how human beings achieve efficient recognition of others’ facial expressions in cognitive neuroscience, and it has been identified that specific cortical regions show preferential activation to facial expressions in previous studies. However, the potential contributions of the connectivity patterns in the processing of facial expressions remained unclear. The present functional magnetic resonance imaging (fMRI) study explored whether facial expressions could be decoded from the functional connectivity (FC) patterns using multivariate pattern analysis combined with machine learning algorithms (fcMVPA). We employed a block design experiment and collected neural activities while participants viewed facial expressions of six basic emotions (anger, disgust, fear, joy, sadness, and surprise). Both static and dynamic expression stimuli were included in our study. A behavioral experiment after scanning confirmed the validity of the facial stimuli presented during the fMRI experiment with classification accuracies and emotional intensities. We obtained whole-brain FC patterns for each facial expression and found that both static and dynamic facial expressions could be successfully decoded from the FC patterns. Moreover, we identified the expression-discriminative networks for the static and dynamic facial expressions, which span beyond the conventional face-selective areas. Overall, these results reveal that large-scale FC patterns may also contain rich expression information to accurately decode facial expressions, suggesting a novel mechanism, which includes general interactions between distributed brain regions, and that contributes to the human facial expression recognition. PMID:29615882

Chemopreventive agents alters global gene expression pattern: predicting their mode of action and targets.

PubMed

Narayanan, Bhagavathi A

2006-12-01

Chemoprevention has the potential to be a major component of colon, breast, prostate and lung cancer control. Epidemiological, experimental, and clinical studies provide evidence that antioxidants, anti-inflammatory agents, n-3 polyunsaturated fatty acids and several other phytochemicals possess unique modes of action against cancer growth. However, the mode of action of several of these agents at the gene transcription level is not completely understood. Completion of the human genome sequence and the advent of DNA microarrays using cDNAs enhanced the detection and identification of hundreds of differentially expressed genes in response to anticancer drugs or chemopreventive agents. In this review, we are presenting an extensive analysis of the key findings from studies using potential chemopreventive agents on global gene expression patterns, which lead to the identification of cancer drug targets. The summary of the study reports discussed in this review explains the extent of gene alterations mediated by more than 20 compounds including antioxidants, fatty acids, NSAIDs, phytochemicals, retinoids, selenium, vitamins, aromatase inhibitor, lovastatin, oltipraz, salvicine, and zinc. The findings from these studies further reveal the utility of DNA microarray in characterizing and quantifying the differentially expressed genes that are possibly reprogrammed by the above agents against colon, breast, prostate, lung, liver, pancreatic and other cancer types. Phenolic antioxidant resveratrol found in berries and grapes inhibits the formation of prostate tumors by acting on the regulatory genes such as p53 while activating a cascade of genes involved in cell cycle and apoptosis including p300, Apaf-1, cdk inhibitor p21, p57 (KIP2), p53 induced Pig 7, Pig 8, Pig 10, cyclin D, DNA fragmentation factor 45. The group of genes significantly altered by selenium includes cyclin D1, cdk5, cdk4, cdk2, cdc25A and GADD 153. Vitamine D shows impact on p21(Waf1/Cip1) p27 cyclin B and cyclin A1. Genomic expression profile with vitamin D indicated differential expression of gene targets such as c-JUN, JUNB, JUND, FREAC-1/FoxF1, ZNF-44/KOX7, plectin, filamin, and keratin-13, involved in antiproliferative, differentiation pathways. The agent UBEIL has a remarkable effect on cyclin D1. Curcumin mediated NrF2 pathway significantly altered p21(Waf1/Cip1) levels. Aromatase inhibitors affected the expression of cyclin D1. Interestingly, few dietary compounds listed in this review also have effect on APC, cdk inhibitors p21(Waf1/Cip1) and p27. Tea polyphenol EGCG has a significant effect on TGF-beta expression, while several other earlier studies have shown its effect on cell cycle regulatory proteins. This review article reveals potential chemoprevention drug targets, which are mainly centered on cell cycle regulatory pathway genes in cancer.

An optimized ERP brain-computer interface based on facial expression changes.

PubMed

Jin, Jing; Daly, Ian; Zhang, Yu; Wang, Xingyu; Cichocki, Andrzej

2014-06-01

Interferences from spatially adjacent non-target stimuli are known to evoke event-related potentials (ERPs) during non-target flashes and, therefore, lead to false positives. This phenomenon was commonly seen in visual attention-based brain-computer interfaces (BCIs) using conspicuous stimuli and is known to adversely affect the performance of BCI systems. Although users try to focus on the target stimulus, they cannot help but be affected by conspicuous changes of the stimuli (such as flashes or presenting images) which were adjacent to the target stimulus. Furthermore, subjects have reported that conspicuous stimuli made them tired and annoyed. In view of this, the aim of this study was to reduce adjacent interference, annoyance and fatigue using a new stimulus presentation pattern based upon facial expression changes. Our goal was not to design a new pattern which could evoke larger ERPs than the face pattern, but to design a new pattern which could reduce adjacent interference, annoyance and fatigue, and evoke ERPs as good as those observed during the face pattern. Positive facial expressions could be changed to negative facial expressions by minor changes to the original facial image. Although the changes are minor, the contrast is big enough to evoke strong ERPs. In this paper, a facial expression change pattern between positive and negative facial expressions was used to attempt to minimize interference effects. This was compared against two different conditions, a shuffled pattern containing the same shapes and colours as the facial expression change pattern, but without the semantic content associated with a change in expression, and a face versus no face pattern. Comparisons were made in terms of classification accuracy and information transfer rate as well as user supplied subjective measures. The results showed that interferences from adjacent stimuli, annoyance and the fatigue experienced by the subjects could be reduced significantly (p < 0.05) by using the facial expression change patterns in comparison with the face pattern. The offline results show that the classification accuracy of the facial expression change pattern was significantly better than that of the shuffled pattern (p < 0.05) and the face pattern (p < 0.05). The facial expression change pattern presented in this paper reduced interference from adjacent stimuli and decreased the fatigue and annoyance experienced by BCI users significantly (p < 0.05) compared to the face pattern.

An optimized ERP brain-computer interface based on facial expression changes

NASA Astrophysics Data System (ADS)

Jin, Jing; Daly, Ian; Zhang, Yu; Wang, Xingyu; Cichocki, Andrzej

2014-06-01

Objective. Interferences from spatially adjacent non-target stimuli are known to evoke event-related potentials (ERPs) during non-target flashes and, therefore, lead to false positives. This phenomenon was commonly seen in visual attention-based brain-computer interfaces (BCIs) using conspicuous stimuli and is known to adversely affect the performance of BCI systems. Although users try to focus on the target stimulus, they cannot help but be affected by conspicuous changes of the stimuli (such as flashes or presenting images) which were adjacent to the target stimulus. Furthermore, subjects have reported that conspicuous stimuli made them tired and annoyed. In view of this, the aim of this study was to reduce adjacent interference, annoyance and fatigue using a new stimulus presentation pattern based upon facial expression changes. Our goal was not to design a new pattern which could evoke larger ERPs than the face pattern, but to design a new pattern which could reduce adjacent interference, annoyance and fatigue, and evoke ERPs as good as those observed during the face pattern. Approach. Positive facial expressions could be changed to negative facial expressions by minor changes to the original facial image. Although the changes are minor, the contrast is big enough to evoke strong ERPs. In this paper, a facial expression change pattern between positive and negative facial expressions was used to attempt to minimize interference effects. This was compared against two different conditions, a shuffled pattern containing the same shapes and colours as the facial expression change pattern, but without the semantic content associated with a change in expression, and a face versus no face pattern. Comparisons were made in terms of classification accuracy and information transfer rate as well as user supplied subjective measures. Main results. The results showed that interferences from adjacent stimuli, annoyance and the fatigue experienced by the subjects could be reduced significantly (p < 0.05) by using the facial expression change patterns in comparison with the face pattern. The offline results show that the classification accuracy of the facial expression change pattern was significantly better than that of the shuffled pattern (p < 0.05) and the face pattern (p < 0.05). Significance. The facial expression change pattern presented in this paper reduced interference from adjacent stimuli and decreased the fatigue and annoyance experienced by BCI users significantly (p < 0.05) compared to the face pattern.

Comparison of tests for spatial heterogeneity on data with global clustering patterns and outliers

PubMed Central

Jackson, Monica C; Huang, Lan; Luo, Jun; Hachey, Mark; Feuer, Eric

2009-01-01

Background The ability to evaluate geographic heterogeneity of cancer incidence and mortality is important in cancer surveillance. Many statistical methods for evaluating global clustering and local cluster patterns are developed and have been examined by many simulation studies. However, the performance of these methods on two extreme cases (global clustering evaluation and local anomaly (outlier) detection) has not been thoroughly investigated. Methods We compare methods for global clustering evaluation including Tango's Index, Moran's I, and Oden's I*pop; and cluster detection methods such as local Moran's I and SaTScan elliptic version on simulated count data that mimic global clustering patterns and outliers for cancer cases in the continental United States. We examine the power and precision of the selected methods in the purely spatial analysis. We illustrate Tango's MEET and SaTScan elliptic version on a 1987-2004 HIV and a 1950-1969 lung cancer mortality data in the United States. Results For simulated data with outlier patterns, Tango's MEET, Moran's I and I*pop had powers less than 0.2, and SaTScan had powers around 0.97. For simulated data with global clustering patterns, Tango's MEET and I*pop (with 50% of total population as the maximum search window) had powers close to 1. SaTScan had powers around 0.7-0.8 and Moran's I has powers around 0.2-0.3. In the real data example, Tango's MEET indicated the existence of global clustering patterns in both the HIV and lung cancer mortality data. SaTScan found a large cluster for HIV mortality rates, which is consistent with the finding from Tango's MEET. SaTScan also found clusters and outliers in the lung cancer mortality data. Conclusion SaTScan elliptic version is more efficient for outlier detection compared with the other methods evaluated in this article. Tango's MEET and Oden's I*pop perform best in global clustering scenarios among the selected methods. The use of SaTScan for data with global clustering patterns should be used with caution since SatScan may reveal an incorrect spatial pattern even though it has enough power to reject a null hypothesis of homogeneous relative risk. Tango's method should be used for global clustering evaluation instead of SaTScan. PMID:19822013

Comparison of tests for spatial heterogeneity on data with global clustering patterns and outliers.

PubMed

Jackson, Monica C; Huang, Lan; Luo, Jun; Hachey, Mark; Feuer, Eric

2009-10-12

The ability to evaluate geographic heterogeneity of cancer incidence and mortality is important in cancer surveillance. Many statistical methods for evaluating global clustering and local cluster patterns are developed and have been examined by many simulation studies. However, the performance of these methods on two extreme cases (global clustering evaluation and local anomaly (outlier) detection) has not been thoroughly investigated. We compare methods for global clustering evaluation including Tango's Index, Moran's I, and Oden's I*(pop); and cluster detection methods such as local Moran's I and SaTScan elliptic version on simulated count data that mimic global clustering patterns and outliers for cancer cases in the continental United States. We examine the power and precision of the selected methods in the purely spatial analysis. We illustrate Tango's MEET and SaTScan elliptic version on a 1987-2004 HIV and a 1950-1969 lung cancer mortality data in the United States. For simulated data with outlier patterns, Tango's MEET, Moran's I and I*(pop) had powers less than 0.2, and SaTScan had powers around 0.97. For simulated data with global clustering patterns, Tango's MEET and I*(pop) (with 50% of total population as the maximum search window) had powers close to 1. SaTScan had powers around 0.7-0.8 and Moran's I has powers around 0.2-0.3. In the real data example, Tango's MEET indicated the existence of global clustering patterns in both the HIV and lung cancer mortality data. SaTScan found a large cluster for HIV mortality rates, which is consistent with the finding from Tango's MEET. SaTScan also found clusters and outliers in the lung cancer mortality data. SaTScan elliptic version is more efficient for outlier detection compared with the other methods evaluated in this article. Tango's MEET and Oden's I*(pop) perform best in global clustering scenarios among the selected methods. The use of SaTScan for data with global clustering patterns should be used with caution since SatScan may reveal an incorrect spatial pattern even though it has enough power to reject a null hypothesis of homogeneous relative risk. Tango's method should be used for global clustering evaluation instead of SaTScan.

Functional genomics annotation of a statistical epistasis network associated with bladder cancer susceptibility.

PubMed

Hu, Ting; Pan, Qinxin; Andrew, Angeline S; Langer, Jillian M; Cole, Michael D; Tomlinson, Craig R; Karagas, Margaret R; Moore, Jason H

2014-04-11

Several different genetic and environmental factors have been identified as independent risk factors for bladder cancer in population-based studies. Recent studies have turned to understanding the role of gene-gene and gene-environment interactions in determining risk. We previously developed the bioinformatics framework of statistical epistasis networks (SEN) to characterize the global structure of interacting genetic factors associated with a particular disease or clinical outcome. By applying SEN to a population-based study of bladder cancer among Caucasians in New Hampshire, we were able to identify a set of connected genetic factors with strong and significant interaction effects on bladder cancer susceptibility. To support our statistical findings using networks, in the present study, we performed pathway enrichment analyses on the set of genes identified using SEN, and found that they are associated with the carcinogen benzo[a]pyrene, a component of tobacco smoke. We further carried out an mRNA expression microarray experiment to validate statistical genetic interactions, and to determine if the set of genes identified in the SEN were differentially expressed in a normal bladder cell line and a bladder cancer cell line in the presence or absence of benzo[a]pyrene. Significant nonrandom sets of genes from the SEN were found to be differentially expressed in response to benzo[a]pyrene in both the normal bladder cells and the bladder cancer cells. In addition, the patterns of gene expression were significantly different between these two cell types. The enrichment analyses and the gene expression microarray results support the idea that SEN analysis of bladder in population-based studies is able to identify biologically meaningful statistical patterns. These results bring us a step closer to a systems genetic approach to understanding cancer susceptibility that integrates population and laboratory-based studies.

Differential protein expression patterns between planktonic and biofilm cells of Salmonella enterica serovar Enteritidis PT4 on stainless steel surface.

PubMed

Giaouris, Efstathios; Samoilis, Georgios; Chorianopoulos, Nikos; Ercolini, Danilo; Nychas, George-John

2013-03-01

In the present study, the proteome of a strain of S. enterica serovar Enteritidis PT4, grown either as biofilm on stainless steel surface or as free-floating (planktonic) in Brain Heart (BH) broth, was investigated in order to detect the strong differences in whole-cell protein expression patterns between the two growth styles. The proteins extracted from both types of cells were subjected to 2-D PAGE, followed by in-gel tryptic digestion, extraction, subsequent MALDI-TOF mass spectrometry (MS) analysis and finally database searches for protein identification. Using this approach, 30 proteins were identified as differentially expressed between the two growth modes on an "on-off" basis, that is, proteins that were detected in one case but not in the other. In particular, 20 and 10 proteins were identified in biofilm and planktonic-grown cells, respectively. The group of proteins whose expression was visible only during biofilm growth included proteins involved in global regulation and stress response (ArcA, BtuE, Dps, OsmY, SspA, TrxA, YbbN and YhbO), nutrient transport (Crr, DppA, Fur and SufC), degradation and energy metabolism (GcvT, GpmA, RibB), detoxification (SseA and YibF), DNA metabolism (SSB), curli production (CsgF), and murein synthesis (MipA). To summarize, this study demonstrates that biofilm growth of S. Enteritidis causes distinct changes in protein expression and offers valuable new data regarding some of the proteins presumably involved in this process. The putative role of these proteins in the maintenance of a biofilm community in Salmonella and other bacteria is discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

Integrated analyses of microRNAs demonstrate their widespread influence on gene expression in high-grade serous ovarian carcinoma.

PubMed

Creighton, Chad J; Hernandez-Herrera, Anadulce; Jacobsen, Anders; Levine, Douglas A; Mankoo, Parminder; Schultz, Nikolaus; Du, Ying; Zhang, Yiqun; Larsson, Erik; Sheridan, Robert; Xiao, Weimin; Spellman, Paul T; Getz, Gad; Wheeler, David A; Perou, Charles M; Gibbs, Richard A; Sander, Chris; Hayes, D Neil; Gunaratne, Preethi H

2012-01-01

The Cancer Genome Atlas (TCGA) Network recently comprehensively catalogued the molecular aberrations in 487 high-grade serous ovarian cancers, with much remaining to be elucidated regarding the microRNAs (miRNAs). Here, using TCGA ovarian data, we surveyed the miRNAs, in the context of their predicted gene targets. Integration of miRNA and gene patterns yielded evidence that proximal pairs of miRNAs are processed from polycistronic primary transcripts, and that intronic miRNAs and their host gene mRNAs derive from common transcripts. Patterns of miRNA expression revealed multiple tumor subtypes and a set of 34 miRNAs predictive of overall patient survival. In a global analysis, miRNA:mRNA pairs anti-correlated in expression across tumors showed a higher frequency of in silico predicted target sites in the mRNA 3'-untranslated region (with less frequency observed for coding sequence and 5'-untranslated regions). The miR-29 family and predicted target genes were among the most strongly anti-correlated miRNA:mRNA pairs; over-expression of miR-29a in vitro repressed several anti-correlated genes (including DNMT3A and DNMT3B) and substantially decreased ovarian cancer cell viability. This study establishes miRNAs as having a widespread impact on gene expression programs in ovarian cancer, further strengthening our understanding of miRNA biology as it applies to human cancer. As with gene transcripts, miRNAs exhibit high diversity reflecting the genomic heterogeneity within a clinically homogeneous disease population. Putative miRNA:mRNA interactions, as identified using integrative analysis, can be validated. TCGA data are a valuable resource for the identification of novel tumor suppressive miRNAs in ovarian as well as other cancers.

Systematical analysis of cutaneous squamous cell carcinoma network of microRNAs, transcription factors, and target and host genes.

PubMed

Wang, Ning; Xu, Zhi-Wen; Wang, Kun-Hao

2014-01-01

MicroRNAs (miRNAs) are small non-coding RNA molecules found in multicellular eukaryotes which are implicated in development of cancer, including cutaneous squamous cell carcinoma (cSCC). Expression is controlled by transcription factors (TFs) that bind to specific DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to messenger RNA. Interactions result in biological signal control networks. Molecular components involved in cSCC were here assembled at abnormally expressed, related and global levels. Networks at these three levels were constructed with corresponding biological factors in term of interactions between miRNAs and target genes, TFs and miRNAs, and host genes and miRNAs. Up/down regulation or mutation of the factors were considered in the context of the regulation and significant patterns were extracted. Participants of the networks were evaluated based on their expression and regulation of other factors. Sub-networks with two core TFs, TP53 and EIF2C2, as the centers are identified. These share self-adapt feedback regulation in which a mutual restraint exists. Up or down regulation of certain genes and miRNAs are discussed. Some, for example the expression of MMP13, were in line with expectation while others, including FGFR3, need further investigation of their unexpected behavior. The present research suggests that dozens of components, miRNAs, TFs, target genes and host genes included, unite as networks through their regulation to function systematically in human cSCC. Networks built under the currently available sources provide critical signal controlling pathways and frequent patterns. Inappropriate controlling signal flow from abnormal expression of key TFs may push the system into an incontrollable situation and therefore contributes to cSCC development.

Global Dosage Compensation Is Ubiquitous in Lepidoptera, but Counteracted by the Masculinization of the Z Chromosome

PubMed Central

Huylmans, Ann Kathrin; Macon, Ariana; Vicoso, Beatriz

2017-01-01

Abstract While chromosome-wide dosage compensation of the X chromosome has been found in many species, studies in ZW clades have indicated that compensation of the Z is more localized and/or incomplete. In the ZW Lepidoptera, some species show complete compensation of the Z chromosome, while others lack full equalization, but what drives these inconsistencies is unclear. Here, we compare patterns of male and female gene expression on the Z chromosome of two closely related butterfly species, Papilio xuthus and Papilio machaon, and in multiple tissues of two moths species, Plodia interpunctella and Bombyx mori, which were previously found to differ in the extent to which they equalize Z-linked gene expression between the sexes. We find that, while some species and tissues seem to have incomplete dosage compensation, this is in fact due to the accumulation of male-biased genes and the depletion of female-biased genes on the Z chromosome. Once this is accounted for, the Z chromosome is fully compensated in all four species, through the up-regulation of Z expression in females and in some cases additional down-regulation in males. We further find that both sex-biased genes and Z-linked genes have increased rates of expression divergence in this clade, and that this can lead to fast shifts in patterns of gene expression even between closely related species. Taken together, these results show that the uneven distribution of sex-biased genes on sex chromosomes can confound conclusions about dosage compensation and that Z chromosome-wide dosage compensation is not only possible but ubiquitous among Lepidoptera. PMID:28957502

Global DNA methylation analysis reveals miR-214-3p contributes to cisplatin resistance in pediatric intracranial nongerminomatous malignant germ cell tumors.

PubMed

Hsieh, Tsung-Han; Liu, Yun-Ru; Chang, Ting-Yu; Liang, Muh-Lii; Chen, Hsin-Hung; Wang, Hsei-Wei; Yen, Yun; Wong, Tai-Tong

2018-03-27

Pediatric central nervous system germ cell tumors (CNSGCTs) are rare and heterogeneous neoplasms, which can be divided into germinomas and nongerminomatous germ cell tumors (NGGCTs). NGGCTs are further subdivided into mature teratomas and nongerminomatous malignant GCTs (NGMGCTs). Clinical outcomes suggest that NGMGCTs have poor prognosis and survival and that they require more extensive radiotherapy and adjuvant chemotherapy. However, the mechanisms underlying this difference are still unclear. DNA methylation alteration is generally acknowledged to cause therapeutic resistance in cancers. We hypothesized that the pediatric NGMGCTs exhibit a different genome-wide DNA methylation pattern, which is involved in the mechanism of its therapeutic resistance. We performed methylation and hydroxymethylation DNA immunoprecipitation sequencing, mRNA expression microarray, and small RNA sequencing (smRNA-seq) to determine methylation-regulated genes, including microRNAs (miRNAs). The expression levels of 97 genes and 8 miRNAs were correlated with promoter DNA methylation and hydroxymethylation status, such as the miR-199/-214 cluster, and treatment with DNA demethylating agent 5-aza-2'-deoxycytidine elevated its expression level. Furthermore, smRNA-seq analysis showed 27 novel miRNA candidates with differential expression between germinomas and NGMGCTs. Overexpresssion of miR-214-3p in NCCIT cells leads to reduced expression of the pro-apoptotic protein BCL2-like 11 and induces cisplatin resistance. We interrogated the differential DNA methylation patterns between germinomas and NGMGCTs and proposed a mechanism for chemoresistance in NGMGCTs. In addition, our sequencing data provide a roadmap for further pediatric CNSGCT research and potential targets for the development of new therapeutic strategies.

Transcriptome analysis of the painted lady butterfly, Vanessa cardui during wing color pattern development.

PubMed

Connahs, Heidi; Rhen, Turk; Simmons, Rebecca B

2016-03-31

Butterfly wing color patterns are an important model system for understanding the evolution and development of morphological diversity and animal pigmentation. Wing color patterns develop from a complex network composed of highly conserved patterning genes and pigmentation pathways. Patterning genes are involved in regulating pigment synthesis however the temporal expression dynamics of these interacting networks is poorly understood. Here, we employ next generation sequencing to examine expression patterns of the gene network underlying wing development in the nymphalid butterfly, Vanessa cardui. We identified 9, 376 differentially expressed transcripts during wing color pattern development, including genes involved in patterning, pigmentation and gene regulation. Differential expression of these genes was highest at the pre-ommochrome stage compared to early pupal and late melanin stages. Overall, an increasing number of genes were down-regulated during the progression of wing development. We observed dynamic expression patterns of a large number of pigment genes from the ommochrome, melanin and also pteridine pathways, including contrasting patterns of expression for paralogs of the yellow gene family. Surprisingly, many patterning genes previously associated with butterfly pattern elements were not significantly up-regulated at any time during pupation, although many other transcription factors were differentially expressed. Several genes involved in Notch signaling were significantly up-regulated during the pre-ommochrome stage including slow border cells, bunched and pebbles; the function of these genes in the development of butterfly wings is currently unknown. Many genes involved in ecdysone signaling were also significantly up-regulated during early pupal and late melanin stages and exhibited opposing patterns of expression relative to the ecdysone receptor. Finally, a comparison across four butterfly transcriptomes revealed 28 transcripts common to all four species that have no known homologs in other metazoans. This study provides a comprehensive list of differentially expressed transcripts during wing development, revealing potential candidate genes that may be involved in regulating butterfly wing patterns. Some differentially expressed genes have no known homologs possibly representing genes unique to butterflies. Results from this study also indicate that development of nymphalid wing patterns may arise not only from melanin and ommochrome pigments but also the pteridine pigment pathway.

Analyzing Global Components in Developmental Dyscalculia and Dyslexia.

PubMed

Filippo, Gloria Di; Zoccolotti, Pierluigi

2018-01-01

The study examined whether developmental deficits in reading and numerical skills could be expressed in terms of global factors by reference to the rate and amount (RAM) and difference engine (DEM) models. From a sample of 325 fifth grade children, we identified 5 children with dyslexia, 16 with dyscalculia, 7 with a "mixed pattern," and 49 control children. Children were asked to read aloud words presented individually that varied for frequency and length and to respond (either vocally or manually) to a series of simple number tasks (addition, subtraction, number reading, and number comparisons). Reaction times were measured. Results indicated that the deficit of children with dyscalculia and children with a mixed pattern on numerical tasks could be explained by a single global factor, similarly to the reading deficit shown by children with dyslexia. As predicted by the DEM, increases in task difficulty were accompanied by a corresponding increase in inter-individual variability for both the reading and numerical tasks. These relationships were constant across the four groups of children but differed in terms of slope and intercept on the x -axis, indicating that two different general rules underlie performance in reading and numerical skills. The study shows for the first time that, as previously shown for reading, also numerical performance can be explained with reference to a global factor. The advantage of this approach is that it takes into account the over-additivity effect, i.e., the presence of larger group differences in the case of more difficult conditions over and above the characteristics of the experimental conditions. It is concluded that reference to models such as the RAM and DEM can be useful in delineating the characteristics of the dyscalculic deficit as well as in the description of co-morbid disturbances, as in the case of dyslexia and dyscalculia.

A remotely sensed pigment index reveals photosynthetic phenology in evergreen conifers

PubMed Central

Huemmrich, K. Fred; Ensminger, Ingo; Garrity, Steven; Noormets, Asko; Peñuelas, Josep

2016-01-01

In evergreen conifers, where the foliage amount changes little with season, accurate detection of the underlying “photosynthetic phenology” from satellite remote sensing has been difficult, presenting challenges for global models of ecosystem carbon uptake. Here, we report a close correspondence between seasonally changing foliar pigment levels, expressed as chlorophyll/carotenoid ratios, and evergreen photosynthetic activity, leading to a “chlorophyll/carotenoid index” (CCI) that tracks evergreen photosynthesis at multiple spatial scales. When calculated from NASA’s Moderate Resolution Imaging Spectroradiometer satellite sensor, the CCI closely follows the seasonal patterns of daily gross primary productivity of evergreen conifer stands measured by eddy covariance. This discovery provides a way of monitoring evergreen photosynthetic activity from optical remote sensing, and indicates an important regulatory role for carotenoid pigments in evergreen photosynthesis. Improved methods of monitoring photosynthesis from space can improve our understanding of the global carbon budget in a warming world of changing vegetation phenology. PMID:27803333

Genomic and transcriptomic evidence for scavenging of diverse organic compounds by widespread deep-sea archaea.

PubMed

Li, Meng; Baker, Brett J; Anantharaman, Karthik; Jain, Sunit; Breier, John A; Dick, Gregory J

2015-11-17

Microbial activity is one of the most important processes to mediate the flux of organic carbon from the ocean surface to the seafloor. However, little is known about the microorganisms that underpin this key step of the global carbon cycle in the deep oceans. Here we present genomic and transcriptomic evidence that five ubiquitous archaeal groups actively use proteins, carbohydrates, fatty acids and lipids as sources of carbon and energy at depths ranging from 800 to 4,950 m in hydrothermal vent plumes and pelagic background seawater across three different ocean basins. Genome-enabled metabolic reconstructions and gene expression patterns show that these marine archaea are motile heterotrophs with extensive mechanisms for scavenging organic matter. Our results shed light on the ecological and physiological properties of ubiquitous marine archaea and highlight their versatile metabolic strategies in deep oceans that might play a critical role in global carbon cycling.

A remotely sensed pigment index reveals photosynthetic phenology in evergreen conifers.

PubMed

Gamon, John A; Huemmrich, K Fred; Wong, Christopher Y S; Ensminger, Ingo; Garrity, Steven; Hollinger, David Y; Noormets, Asko; Peñuelas, Josep

2016-11-15

In evergreen conifers, where the foliage amount changes little with season, accurate detection of the underlying "photosynthetic phenology" from satellite remote sensing has been difficult, presenting challenges for global models of ecosystem carbon uptake. Here, we report a close correspondence between seasonally changing foliar pigment levels, expressed as chlorophyll/carotenoid ratios, and evergreen photosynthetic activity, leading to a "chlorophyll/carotenoid index" (CCI) that tracks evergreen photosynthesis at multiple spatial scales. When calculated from NASA's Moderate Resolution Imaging Spectroradiometer satellite sensor, the CCI closely follows the seasonal patterns of daily gross primary productivity of evergreen conifer stands measured by eddy covariance. This discovery provides a way of monitoring evergreen photosynthetic activity from optical remote sensing, and indicates an important regulatory role for carotenoid pigments in evergreen photosynthesis. Improved methods of monitoring photosynthesis from space can improve our understanding of the global carbon budget in a warming world of changing vegetation phenology.

Slack channels expressed in sensory neurons control neuropathic pain in mice.

PubMed

Lu, Ruirui; Bausch, Anne E; Kallenborn-Gerhardt, Wiebke; Stoetzer, Carsten; Debruin, Natasja; Ruth, Peter; Geisslinger, Gerd; Leffler, Andreas; Lukowski, Robert; Schmidtko, Achim

2015-01-21

Slack (Slo2.2) is a sodium-activated potassium channel that regulates neuronal firing activities and patterns. Previous studies identified Slack in sensory neurons, but its contribution to acute and chronic pain in vivo remains elusive. Here we generated global and sensory neuron-specific Slack mutant mice and analyzed their behavior in various animal models of pain. Global ablation of Slack led to increased hypersensitivity in models of neuropathic pain, whereas the behavior in models of inflammatory and acute nociceptive pain was normal. Neuropathic pain behaviors were also exaggerated after ablation of Slack selectively in sensory neurons. Notably, the Slack opener loxapine ameliorated persisting neuropathic pain behaviors. In conclusion, Slack selectively controls the sensory input in neuropathic pain states, suggesting that modulating its activity might represent a novel strategy for management of neuropathic pain. Copyright © 2015 the authors 0270-6474/15/351125-11$15.00/0.

Nearest pattern interaction and global pattern formation

NASA Astrophysics Data System (ADS)

Jeong, Seong-Ok; Moon, Hie-Tae; Ko, Tae-Wook

2000-12-01

We studied the effect of nearest pattern interaction on a global pattern formation in a two-dimensional space, where patterns are to grow initially from a noise in the presence of a periodic supply of energy. Although our approach is general, we found that this study is relevant in particular to the pattern formation on a periodically vibrated granular layer, as it gives a unified perspective of the experimentally observed pattern dynamics such as oscillon and stripe formations, skew-varicose and crossroll instabilities, and also a kink formation and decoration.

Can global hydrological models reproduce large scale river flood regimes?

NASA Astrophysics Data System (ADS)

Eisner, Stephanie; Flörke, Martina

2013-04-01

River flooding remains one of the most severe natural hazards. On the one hand, major flood events pose a serious threat to human well-being, causing deaths and considerable economic damage. On the other hand, the periodic occurrence of flood pulses is crucial to maintain the functioning of riverine floodplains and wetlands, and to preserve the ecosystem services the latter provide. In many regions, river floods reveal a distinct seasonality, i.e. they occur at a particular time during the year. This seasonality is related to regionally dominant flood generating processes which can be expressed in river flood types. While in data-rich regions (esp. Europe and North America) the analysis of flood regimes can be based on observed river discharge time series, this data is sparse or lacking in many other regions of the world. This gap of knowledge can be filled by global modeling approaches. However, to date most global modeling studies have focused on mean annual or monthly water availability and their change over time while simulating discharge extremes, both floods and droughts, still remains a challenge for large scale hydrological models. This study will explore the ability of the global hydrological model WaterGAP3 to simulate the large scale patterns of river flood regimes, represented by seasonal pattern and the dominant flood type. WaterGAP3 simulates the global terrestrial water balance on a 5 arc minute spatial grid (excluding Greenland and Antarctica) at a daily time step. The model accounts for human interference on river flow, i.e. water abstraction for various purposes, e.g. irrigation, and flow regulation by large dams and reservoirs. Our analysis will provide insight in the general ability of global hydrological models to reproduce river flood regimes and thus will promote the creation of a global map of river flood regimes to provide a spatially inclusive and comprehensive picture. Understanding present-day flood regimes can support both flood risk analysis and the assessment of potential regional impacts of climate change on river flooding.

Diverse Responses of Global Vegetation to Climate Changes: Spatial Patterns and Time-lag Effects

NASA Astrophysics Data System (ADS)

Wu, D.; Zhao, X.; Zhou, T.; Huang, K.; Xu, W.

2014-12-01

Global climate changes have enormous influences on vegetation growth, meanwhile, response of vegetation to climate express space diversity and time-lag effects, which account for spatial-temporal disparities of climate change and spatial heterogeneity of ecosystem. Revelation of this phenomenon will help us further understanding the impact of climate change on vegetation. Assessment and forecast of global environmental change can be also improved under further climate change. Here we present space diversity and time-lag effects patterns of global vegetation respond to three climate factors (temperature, precipitation and solar radiation) based on quantitative analysis of satellite data (NDVI) and Climate data (Climate Research Unit). We assessed the time-lag effects of global vegetation to main climate factors based on the great correlation fitness between NDVI and the three climate factors respectively among 0-12 months' temporal lags. On this basis, integrated response model of NDVI and the three climate factors was built to analyze contribution of different climate factors to vegetation growth with multiple regression model and partial correlation model. In the result, different vegetation types have distinct temporal lags to the three climate factors. For the precipitation, temporal lags of grasslands are the shortest while the evergreen broad-leaf forests are the longest, which means that grasslands are more sensitive to precipitation than evergreen broad-leaf forests. Analysis of different climate factors' contribution to vegetation reveal that vegetation are dominated by temperature in the high northern latitudes; they are mainly restricted by precipitation in arid and semi-arid areas (Australia, Western America); in humid areas of low and intermediate latitudes (Amazon, Eastern America), vegetation are mainly influenced by solar radiation. Our results reveal the time-lag effects and major driving factors of global vegetation growth and explain the spatiotemporal variations of global vegetation in last 30 years. Significantly, it is as well as in forecasting and assessing the influences of future climate change on the vegetation dynamics. This work was supported by the High Technology Research and Development Program of China (Grant NO.2013AA122801).

Evidence for a role of the oxytocin system, indexed by genetic variation in CD38, in the social bonding effects of expressed gratitude.

PubMed

Algoe, Sara B; Way, Baldwin M

2014-12-01

Oxytocin is thought to play a central role in promoting close social bonds via influence on social interactions. The current investigation targeted interactions involving expressed gratitude between members of romantic relationships because recent evidence suggests gratitude and its expression provides behavioral and psychological 'glue' to bind individuals closer together. Specifically, we took a genetic approach to test the hypothesis that social interactions involving expressed gratitude would be associated with variation in a gene, CD38, which has been shown to affect oxytocin secretion. A polymorphism (rs6449182) that affects CD38 expression was significantly associated with global relationship satisfaction, perceived partner responsiveness and positive emotions (particularly love) after lab-based interactions, observed behavioral expression of gratitude toward a romantic partner in the lab, and frequency of expressed gratitude in daily life. A separate polymorphism in CD38 (rs3796863) previously associated with plasma oxytocin levels and social engagement was also associated with perceived responsiveness in the benefactor after an expression of gratitude. The combined influence of the two polymorphisms was associated with a broad range of gratitude-related behaviors and feelings. The consistent pattern of findings suggests that the oxytocin system is associated with solidifying the glue that binds adults into meaningful and important relationships. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Transcript Profiling Identifies Dynamic Gene Expression Patterns and an Important Role for Nrf2/Keap1 Pathway in the Developing Mouse Esophagus

PubMed Central

Li, Haiyan; Hu, Yuhui; Tevebaugh, Whitney; Yamamoto, Masayuki; Que, Jianwen; Chen, Xiaoxin

2012-01-01

Background and Aims Morphological changes during human and mouse esophageal development have been well characterized. However, changes at the molecular level in the course of esophageal morphogenesis remain unclear. This study aims to globally profile critical genes and signaling pathways during the development of mouse esophagus. By using microarray analysis this study also aims to determine how the Nrf2/Keap1 pathway regulates the morphogenesis of the esophageal epithelium. Methods Gene expression microarrays were used to survey gene expression in the esophagus at three critical phases: specification, metaplasia and maturation. The esophagi were isolated from wild-type, Nrf2−/−, Keap1−/−, or Nrf2−/−Keap1−/− embryos or young adult mice. Array data were statistically analyzed for differentially expressed genes and pathways. Histochemical and immunohistochemical staining were used to verify potential involvement of the Wnt pathway, Pparβ/δ and the PI3K/Akt pathway in the development of esophageal epithelium. Results Dynamic gene expression patterns accompanied the morphological changes of the developing esophagus at critical phases. Particularly, the Nrf2/Keap1 pathway had a baseline activity in the metaplasia phase and was further activated in the maturation phase. The Wnt pathway was active early and became inactive later in the metaplasia phase. In addition, Keap1−/− mice showed increased expression of Nrf2 downstream targets and genes involved in keratinization. Microarray and immunostaining data also suggested that esophageal hyperkeratosis in the Keap1−/− mice was due to activation of Pparβ/δ and the PI3K/Akt pathway. Conclusions Morphological changes of the esophageal epithelium are associated with dynamic changes in gene expression. Nrf2/Keap1 pathway activity is required for maturation of mouse esophageal epithelium. PMID:22567161

Sampling capacity underlies individual differences in human associative learning.

PubMed

Byrom, Nicola C; Murphy, Robin A

2014-04-01

Though much work has studied how external factors, such as stimulus properties, influence generalization of associative strength, there has been limited exploration of the influence that internal dispositions may contribute to stimulus processing. Here we report 2 studies using a modified negative patterning discrimination to test the relationship between global processing and generalization. Global processing was associated with stronger negative patterning discrimination, indicative of limited generalization between distinct stimulus compounds and their constituent elements. In Experiment 2, participants pretrained to adopt global processing similarly showed strong negative patterning discrimination. These results demonstrate considerable individual difference in capacity to engage in negative patterning discrimination and suggest that the tendency toward global processing may be one factor explaining this variability. The need for models of learning to account for this variability in learning is discussed.

Gene Expression Patterns Define Key Transcriptional Events InCell-Cycle Regulation By cAMP And Protein Kinase A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zambon, Alexander C.; Zhang, Lingzhi; Minovitsky, Simon

Although a substantial number of hormones and drugs increase cellular cAMP levels, the global impact of cAMP and its major effector mechanism, protein kinase A (PKA), on gene expression is not known. Here we show that treatment of murine wild-type S49 lymphoma cells for 24 h with 8-(4-chlorophenylthio)-cAMP (8-CPTcAMP), a PKA-selective cAMP analog, alters the expression of approx equal to 4,500 of approx. equal to 13,600 unique genes. By contrast, gene expression was unaltered in Kin- S49 cells (that lack PKA) incubated with 8-CPTcAMP. Changes in mRNA and protein expression of several cell cycle regulators accompanied cAMP-induced G1-phase cell-cycle arrestmore » of wild-type S49 cells. Within 2h, 8-CPT-cAMP altered expression of 152 genes that contain evolutionarily conserved cAMP-response elements within 5 kb of transcriptional start sites, including the circadian clock gene Per1. Thus, cAMP through its activation of PKA produces extensive transcriptional regulation in eukaryotic cells. These transcriptional networks include a primary group of cAMP-response element-containing genes and secondary networks that include the circadian clock.« less

UVB-induced gene expression in the skin of Xiphophorus maculatus Jp 163 B☆

PubMed Central

Yang, Kuan; Boswell, Mikki; Walter, Dylan J.; Downs, Kevin P.; Gaston-Pravia, Kimberly; Garcia, Tzintzuni; Shen, Yingjia; Mitchell, David L.; Walter, Ronald B.

2014-01-01

Xiphophorus fish and interspecies hybrids represent long-standing models to study the genetics underlying spontaneous and induced tumorigenesis. The recent release of the Xiphophorus maculatus genome sequence will allow global genetic regulation studies of genes involved in the inherited susceptibility to UVB-induced melanoma within select backcross hybrids. As a first step toward this goal, we report results of an RNA-Seq approach to identify genes and pathways showing modulated transcription within the skin of X. maculatus Jp 163 B upon UVB exposure. X. maculatus Jp 163 B were exposed to various doses of UVB followed by RNA-Seq analysis at each dose to investigate overall gene expression in each sample. A total of 357 genes with a minimum expression change of 4-fold (p-adj < 0.05) were identified as responsive to UVB. The molecular genetic response of Xiphophorus skin to UVB exposure permitted assessment of; (1) the basal expression level of each transcript for each skin sample, (2) the changes in expression levels for each gene in the transcriptome upon exposure to increasing doses of UVB, and (3) clusters of genes that exhibit similar patterns of change in expression upon UVB exposure. These data provide a foundation for understanding the molecular genetic response of fish skin to UVB exposure. PMID:24556253

Functional expression of dental plaque microbiota.

PubMed

Peterson, Scott N; Meissner, Tobias; Su, Andrew I; Snesrud, Erik; Ong, Ana C; Schork, Nicholas J; Bretz, Walter A

2014-01-01

Dental caries remains a significant public health problem and is considered pandemic worldwide. The prediction of dental caries based on profiling of microbial species involved in disease and equally important, the identification of species conferring dental health has proven more difficult than anticipated due to high interpersonal and geographical variability of dental plaque microbiota. We have used RNA-Seq to perform global gene expression analysis of dental plaque microbiota derived from 19 twin pairs that were either concordant (caries-active or caries-free) or discordant for dental caries. The transcription profiling allowed us to define a functional core microbiota consisting of nearly 60 species. Similarities in gene expression patterns allowed a preliminary assessment of the relative contribution of human genetics, environmental factors and caries phenotype on the microbiota's transcriptome. Correlation analysis of transcription allowed the identification of numerous functional networks, suggesting that inter-personal environmental variables may co-select for groups of genera and species. Analysis of functional role categories allowed the identification of dominant functions expressed by dental plaque biofilm communities, that highlight the biochemical priorities of dental plaque microbes to metabolize diverse sugars and cope with the acid and oxidative stress resulting from sugar fermentation. The wealth of data generated by deep sequencing of expressed transcripts enables a greatly expanded perspective concerning the functional expression of dental plaque microbiota.

Functional expression of dental plaque microbiota

PubMed Central

Peterson, Scott N.; Meissner, Tobias; Su, Andrew I.; Snesrud, Erik; Ong, Ana C.; Schork, Nicholas J.; Bretz, Walter A.

2014-01-01

Dental caries remains a significant public health problem and is considered pandemic worldwide. The prediction of dental caries based on profiling of microbial species involved in disease and equally important, the identification of species conferring dental health has proven more difficult than anticipated due to high interpersonal and geographical variability of dental plaque microbiota. We have used RNA-Seq to perform global gene expression analysis of dental plaque microbiota derived from 19 twin pairs that were either concordant (caries-active or caries-free) or discordant for dental caries. The transcription profiling allowed us to define a functional core microbiota consisting of nearly 60 species. Similarities in gene expression patterns allowed a preliminary assessment of the relative contribution of human genetics, environmental factors and caries phenotype on the microbiota's transcriptome. Correlation analysis of transcription allowed the identification of numerous functional networks, suggesting that inter-personal environmental variables may co-select for groups of genera and species. Analysis of functional role categories allowed the identification of dominant functions expressed by dental plaque biofilm communities, that highlight the biochemical priorities of dental plaque microbes to metabolize diverse sugars and cope with the acid and oxidative stress resulting from sugar fermentation. The wealth of data generated by deep sequencing of expressed transcripts enables a greatly expanded perspective concerning the functional expression of dental plaque microbiota. PMID:25177549

An Integrated Functional Genomics Consortium to Increase Carbon Sequestration in Poplars: Optimizing Aboveground Carbon Gain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karnosky, David F; Podila, G Krishna; Burton, Andrew J

2009-02-17

This project used gene expression patterns from two forest Free-Air CO2 Enrichment (FACE) experiments (Aspen FACE in northern Wisconsin and POPFACE in Italy) to examine ways to increase the aboveground carbon sequestration potential of poplars (Populus). The aim was to use patterns of global gene expression to identify candidate genes for increased carbon sequestration. Gene expression studies were linked to physiological measurements in order to elucidate bottlenecks in carbon acquisition in trees grown in elevated CO2 conditions. Delayed senescence allowing additional carbon uptake late in the growing season, was also examined, and expression of target genes was tested in elitemore » P. deltoides x P. trichocarpa hybrids. In Populus euramericana, gene expression was sensitive to elevated CO2, but the response depended on the developmental age of the leaves. Most differentially expressed genes were upregulated in elevated CO2 in young leaves, while most were downregulated in elevated CO2 in semi-mature leaves. In P. deltoides x P. trichocarpa hybrids, leaf development and leaf quality traits, including leaf area, leaf shape, epidermal cell area, stomatal number, specific leaf area, and canopy senescence were sensitive to elevated CO2. Significant increases under elevated CO2 occurred for both above- and belowground growth in the F-2 generation. Three areas of the genome played a role in determining aboveground growth response to elevated CO2, with three additional areas of the genome important in determining belowground growth responses to elevated CO2. In Populus tremuloides, CO2-responsive genes in leaves were found to differ between two aspen clones that showed different growth responses, despite similarity in many physiological parameters (photosynthesis, stomatal conductance, and leaf area index). The CO2-responsive clone shunted C into pathways associated with active defense/response to stress, carbohydrate/starch biosynthesis and subsequent growth. The CO2-unresponsive clone partitioned C into pathways associated with passive defense and cell wall thickening. These results indicate that there is significant variation in gene expression patterns between different tree genotypes. Consequently, future efforts to improve productivity or other advantageous traits for carbon sequestration should include an examination of genetic variability in CO2 responsiveness.« less

Four not six: Revealing culturally common facial expressions of emotion.

PubMed

Jack, Rachael E; Sun, Wei; Delis, Ioannis; Garrod, Oliver G B; Schyns, Philippe G

2016-06-01

As a highly social species, humans generate complex facial expressions to communicate a diverse range of emotions. Since Darwin's work, identifying among these complex patterns which are common across cultures and which are culture-specific has remained a central question in psychology, anthropology, philosophy, and more recently machine vision and social robotics. Classic approaches to addressing this question typically tested the cross-cultural recognition of theoretically motivated facial expressions representing 6 emotions, and reported universality. Yet, variable recognition accuracy across cultures suggests a narrower cross-cultural communication supported by sets of simpler expressive patterns embedded in more complex facial expressions. We explore this hypothesis by modeling the facial expressions of over 60 emotions across 2 cultures, and segregating out the latent expressive patterns. Using a multidisciplinary approach, we first map the conceptual organization of a broad spectrum of emotion words by building semantic networks in 2 cultures. For each emotion word in each culture, we then model and validate its corresponding dynamic facial expression, producing over 60 culturally valid facial expression models. We then apply to the pooled models a multivariate data reduction technique, revealing 4 latent and culturally common facial expression patterns that each communicates specific combinations of valence, arousal, and dominance. We then reveal the face movements that accentuate each latent expressive pattern to create complex facial expressions. Our data questions the widely held view that 6 facial expression patterns are universal, instead suggesting 4 latent expressive patterns with direct implications for emotion communication, social psychology, cognitive neuroscience, and social robotics. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Genome-wide analysis of the Dof transcription factor gene family reveals soybean-specific duplicable and functional characteristics.

PubMed

Guo, Yong; Qiu, Li-Juan

2013-01-01

The Dof domain protein family is a classic plant-specific zinc-finger transcription factor family involved in a variety of biological processes. There is great diversity in the number of Dof genes in different plants. However, there are only very limited reports on the characterization of Dof transcription factors in soybean (Glycine max). In the present study, 78 putative Dof genes were identified from the whole-genome sequence of soybean. The predicted GmDof genes were non-randomly distributed within and across 19 out of 20 chromosomes and 97.4% (38 pairs) were preferentially retained duplicate paralogous genes located in duplicated regions of the genome. Soybean-specific segmental duplications contributed significantly to the expansion of the soybean Dof gene family. These Dof proteins were phylogenetically clustered into nine distinct subgroups among which the gene structure and motif compositions were considerably conserved. Comparative phylogenetic analysis of these Dof proteins revealed four major groups, similar to those reported for Arabidopsis and rice. Most of the GmDofs showed specific expression patterns based on RNA-seq data analyses. The expression patterns of some duplicate genes were partially redundant while others showed functional diversity, suggesting the occurrence of sub-functionalization during subsequent evolution. Comprehensive expression profile analysis also provided insights into the soybean-specific functional divergence among members of the Dof gene family. Cis-regulatory element analysis of these GmDof genes suggested diverse functions associated with different processes. Taken together, our results provide useful information for the functional characterization of soybean Dof genes by combining phylogenetic analysis with global gene-expression profiling.

Dehydration induced transcriptomic responses in two Tibetan hulless barley (Hordeum vulgare var. nudum) accessions distinguished by drought tolerance.

PubMed

Liang, Junjun; Chen, Xin; Deng, Guangbing; Pan, Zhifen; Zhang, Haili; Li, Qiao; Yang, Kaijun; Long, Hai; Yu, Maoqun

2017-10-11

The harsh environment on the Qinghai-Tibetan Plateau gives Tibetan hulless barley (Hordeum vulgare var. nudum) great ability to resist adversities such as drought, salinity, and low temperature, and makes it a good subject for the analysis of drought tolerance mechanism. To elucidate the specific gene networks and pathways that contribute to its drought tolerance, and for identifying new candidate genes for breeding purposes, we performed a transcriptomic analysis using two accessions of Tibetan hulless barley, namely Z772 (drought-tolerant) and Z013 (drought-sensitive). There were more up-regulated genes of Z772 than Z013 under both mild (5439-VS-2604) and severe (7203-VS-3359) dehydration treatments. Under mild dehydration stress, the pathways exclusively enriched in drought-tolerance genotype Z772 included Protein processing in endoplasmic reticulum, tricarboxylic acid (TCA) cycle, Wax biosynthesis, and Spliceosome. Under severe dehydration stress, the pathways that were mainly enriched in Z772 included Carbon fixation in photosynthetic organisms, Pyruvate metabolism, Porphyrin and chlorophyll metabolism. The main differentially expressed genes (DEGs) in response to dehydration stress and genes whose expression was different between tolerant and sensitive genotypes were presented in this study, respectively. The candidate genes for drought tolerance were selected based on their expression patterns. The RNA-Seq data obtained in this study provided an initial overview on global gene expression patterns and networks that related to dehydration shock in Tibetan hulless barley. Furthermore, these data provided pathways and a targeted set of candidate genes that might be essential for deep analyzing the molecular mechanisms of plant tolerance to drought stress.

Culture medium composition affects the gene expression pattern and in vitro development potential of bovine somatic cell nuclear transfer (SCNT) embryos.

PubMed

Arias, María E; Ross, Pablo J; Felmer, Ricardo N

2013-01-01

Different culture systems have been studied that support development of somatic cell nuclear transfer (SCNT) embryos up to the blastocyst stage. However, the use of sequential and two-step culture systems has been less studied. The objective of the present study was to examine the developmental potential and quality of bovine SCNT embryos cultured in different two-step culture media based on KSOM, SOF and the macromolecules FBS and BSA (K-K/FBS, K-S/BSA and K-K/BSA, respectively). No differences were observed in the cleavage rate for any of the culture systems. However, there was a significant difference (P<0.01) in the rate of blastocyst development, with the K-K/ FBS culture system yielding a higher rate of blastocysts (28%) compared to other treatments (18 and 15%, for K-S/BSA and K-K/BSA, respectively). Although quality of embryos, as assessed by the total number of cells, was not different, the apoptosis index was significantly affected in the sequential culture system (K-S/BSA). Gene expression analysis showed alterations of DNMT1, IGF2, LIF, and PRDX6 genes in embryos cultured in K-S/FBS and of SOD2 in embryos cultured in K-K/BSA. In conclusion, we demonstrated that culture medium may affect not only the developmental potential of SCNT embryos but also, more importantly, the gene expression pattern and apoptotic index, presenting the possibility to manipulate the culture medium composition to modulate global gene expression and improve the overall efficiency of this technique.

Neuroendocrine profiles associated with discrete behavioural variation in Symphodus ocellatus, a species with male alternative reproductive tactics.

PubMed

Nugent, B M; Stiver, K A; Alonzo, S H; Hofmann, H A

2016-10-01

The molecular mechanisms underlying phenotypic plasticity are not well understood. Identifying mechanisms underlying alternative reproductive tactics (ARTs) in species for which the behavioural and fitness consequences of this variation are well characterized provides an opportunity to integrate evolutionary and mechanistic understanding of the maintenance of variation within populations. In the ocellated wrasse Symphodus ocellatus, the behavioural phenotypes of three distinct male morphs (sneakers, satellites and nesting males), which arise from a single genome, have been thoroughly characterized. To determine the neuroendocrine and genomic mechanisms associated with discrete phenotypic variation and ARTs in S. ocellatus in their natural environment, we constructed a whole-brain de novo transcriptome and compared global patterns of gene expression between sexes and male morphs. Next, we quantified circulating cortisol and 11-ketotestosterone (11-kt), mediators of male reproductive behaviours, as well as stress and gonadal steroid hormone receptor expression in the preoptic area, ventral subpallial division of the telencephalon and dorsolateral telencephalon, critical brain regions for social and reproductive behaviours. We found higher levels of 11-kt in nesting males and higher levels of cortisol in sneaker males relative to other male morphs and females. We also identified distinct patterns of brain region-specific hormone receptor expression between males such that most hormone receptors are more highly expressed in satellites and nesting males relative to sneakers and females. Our results establish the neuroendocrine and molecular mechanisms that underlie ARTs in the wild and provide a foundation for experimentally testing hypotheses about the relationship between neuromolecular processes and reproductive success. © 2016 John Wiley & Sons Ltd.

TRANSCRIPTOME ANALYSES REVEAL DIFFERENTIAL GENE EXPRESSION PATTERNS BETWEEN THE LIFE-CYCLE STAGES OF EMILIANIA HUXLEYI (HAPTOPHYTA) AND REFLECT SPECIALIZATION TO DIFFERENT ECOLOGICAL NICHES(1).

PubMed

Rokitta, Sebastian D; de Nooijer, Lennart J; Trimborn, Scarlett; de Vargas, Colomban; Rost, Björn; John, Uwe

2011-08-01

Coccolithophores, especially the abundant, cosmopolitan species Emiliania huxleyi (Lohmann) W. W. Hay et H. P. Mohler, are one of the main driving forces of the oceanic carbonate pump and contribute significantly to global carbon cycling, due to their ability to calcify. A recent study indicates that termination of diploid blooms by viral infection induces life-cycle transition, and speculation has arisen about the role of the haploid, noncalcifying stage in coccolithophore ecology. To explore gene expression patterns in both life-cycle stages, haploid and diploid cells of E. huxleyi (RCC 1217 and RCC 1216) were acclimated to limiting and saturating photon flux densities. Transcriptome analyses were performed to assess differential genomic expression related to different ploidy levels and acclimation light intensities. Analyses indicated that life-cycle stages exhibit different properties of regulating genome expression (e.g., pronounced gene activation and gene silencing in the diploid stage), proteome maintenance (e.g., increased turnover of proteins in the haploid stage), as well as metabolic processing (e.g., pronounced primary metabolism and motility in the haploid stage and calcification in the diploid stage). Furthermore, higher abundances of transcripts related to endocytotic and digestive machinery were observed in the diploid stage. A qualitative feeding experiment indicated that both life-cycle stages are capable of particle uptake (0.5 μm diameter) in late-stationary growth phase. Results showed that the two life-cycle stages represent functionally distinct entities that are evolutionarily shaped to thrive in the environment they typically inhabit. © 2011 Phycological Society of America.

Global View of the Functional Molecular Organization of the Avian Cerebrum: Mirror Images and Functional Columns

PubMed Central

Jarvis, Erich D.; Yu, Jing; Rivas, Miriam V.; Horita, Haruhito; Feenders, Gesa; Whitney, Osceola; Jarvis, Syrus C.; Jarvis, Electra R.; Kubikova, Lubica; Puck, Ana E.P.; Siang-Bakshi, Connie; Martin, Suzanne; McElroy, Michael; Hara, Erina; Howard, Jason; Pfenning, Andreas; Mouritsen, Henrik; Chen, Chun-Chun; Wada, Kazuhiro

2014-01-01

Based on quantitative cluster analyses of 52 constitutively expressed or behaviorally regulated genes in 23 brain regions, we present a global view of telencephalic organization of birds. The patterns of constitutively expressed genes revealed a partial mirror image organization of three major cell populations that wrap above, around, and below the ventricle and adjacent lamina through the mesopallium. The patterns of behaviorally regulated genes revealed functional columns of activation across boundaries of these cell populations, reminiscent of columns through layers of the mammalian cortex. The avian functionally regulated columns were of two types: those above the ventricle and associated mesopallial lamina, formed by our revised dorsal mesopallium, hyperpallium, and intercalated hyperpallium; and those below the ventricle, formed by our revised ventral mesopallium, nidopallium, and intercalated nidopallium. Based on these findings and known connectivity, we propose that the avian pallium has four major cell populations similar to those in mammalian cortex and some parts of the amygdala: 1) a primary sensory input population (intercalated pallium); 2) a secondary intrapallial population (nidopallium/hyperpallium); 3) a tertiary intrapallial population (mesopallium); and 4) a quaternary output population (the arcopallium). Each population contributes portions to columns that control different sensory or motor systems. We suggest that this organization of cell groups forms by expansion of contiguous developmental cell domains that wrap around the lateral ventricle and its extension through the middle of the mesopallium. We believe that the position of the lateral ventricle and its associated mesopallium lamina has resulted in a conceptual barrier to recognizing related cell groups across its border, thereby confounding our understanding of homologies with mammals. PMID:23818122

Application of the Repetitive Behavior Scale-Revised--Italian version--in preschoolers with autism spectrum disorder.

PubMed

Fulceri, Francesca; Narzisi, Antonio; Apicella, Fabio; Balboni, Giulia; Baldini, Sara; Brocchini, Jenny; Domenici, Ilaria; Cerullo, Sonia; Igliozzi, Roberta; Cosenza, Angela; Tancredi, Raffaella; Muratori, Filippo; Calderoni, Sara

2016-01-01

Restricted repetitive and stereotyped patterns of behavior, interests, and activities (RRB) are mandatory features for a diagnosis of Autism Spectrum Disorder (ASD) according to the Diagnostic and Statistical Manual of mental disorders-fifth edition (DSM-5). Despite the strong diagnostic role of RRB, their expressiveness and their relationship with other clinical/demographic features in ASD is not fully elucidated. The Italian version of the Repetitive Behavior Scale-Revised (RBS-R) was applied to a relatively large sample of preschool-aged children with ASD who underwent a comprehensive clinical assessment. The relationship between RRB and sex, age, non-verbal IQ, autism severity, as well as the diagnostic accuracy of the RBS-R were explored. Stereotyped and Ritualistic/Sameness behaviors were the most common RRB in preschoolers with ASD, without widespread differences between males and females. No significant correlations between RRB and chronological age, or non-verbal IQ were detected. The expressiveness of ritualistic/sameness behaviors positively correlated with autism severity, assessed through the Calibrated Severity Score (CSS) derived from the Autism Diagnostic Observation Schedule (ADOS). Receiver Operator Characteristic (ROC) analysis showed high diagnostic accuracy using the Global Rating Score, which represents the judgment of the parents of as the RRB affect the child's life. However, while the Global Rating Score performed well, the remaining subscales did not. This investigation extends the limited research on early pattern and associated features of RRB in young children with ASD. The use of the RBS-R may increase the knowledge of the RRB complexity and variability and in turn improve the diagnostic and therapeutic procedures within the autistic spectrum. Copyright © 2015 Elsevier Ltd. All rights reserved.

Global view of the functional molecular organization of the avian cerebrum: mirror images and functional columns.

PubMed

Jarvis, Erich D; Yu, Jing; Rivas, Miriam V; Horita, Haruhito; Feenders, Gesa; Whitney, Osceola; Jarvis, Syrus C; Jarvis, Electra R; Kubikova, Lubica; Puck, Ana E P; Siang-Bakshi, Connie; Martin, Suzanne; McElroy, Michael; Hara, Erina; Howard, Jason; Pfenning, Andreas; Mouritsen, Henrik; Chen, Chun-Chun; Wada, Kazuhiro

2013-11-01

Based on quantitative cluster analyses of 52 constitutively expressed or behaviorally regulated genes in 23 brain regions, we present a global view of telencephalic organization of birds. The patterns of constitutively expressed genes revealed a partial mirror image organization of three major cell populations that wrap above, around, and below the ventricle and adjacent lamina through the mesopallium. The patterns of behaviorally regulated genes revealed functional columns of activation across boundaries of these cell populations, reminiscent of columns through layers of the mammalian cortex. The avian functionally regulated columns were of two types: those above the ventricle and associated mesopallial lamina, formed by our revised dorsal mesopallium, hyperpallium, and intercalated hyperpallium; and those below the ventricle, formed by our revised ventral mesopallium, nidopallium, and intercalated nidopallium. Based on these findings and known connectivity, we propose that the avian pallium has four major cell populations similar to those in mammalian cortex and some parts of the amygdala: 1) a primary sensory input population (intercalated pallium); 2) a secondary intrapallial population (nidopallium/hyperpallium); 3) a tertiary intrapallial population (mesopallium); and 4) a quaternary output population (the arcopallium). Each population contributes portions to columns that control different sensory or motor systems. We suggest that this organization of cell groups forms by expansion of contiguous developmental cell domains that wrap around the lateral ventricle and its extension through the middle of the mesopallium. We believe that the position of the lateral ventricle and its associated mesopallium lamina has resulted in a conceptual barrier to recognizing related cell groups across its border, thereby confounding our understanding of homologies with mammals. Copyright © 2013 Wiley Periodicals, Inc.

Recent human history governs global ant invasion dynamics

Treesearch

Cleo Bertelsmeier; Sébastien Ollier; Andrew Liebhold; Laurent Keller

2017-01-01

Human trade and travel are breaking down biogeographic barriers, resulting in shifts in the geographical distribution of organisms, yet it remains largely unknown whether different alien species generally follow similar spatiotemporal colonization patterns and how such patterns are driven by trends in global trade. Here, we analyse the global distribution of 241 alien...

Global/local processing of hierarchical visual stimuli in a conflict-choice task by capuchin monkeys (Sapajus spp.).

PubMed

Truppa, Valentina; Carducci, Paola; De Simone, Diego Antonio; Bisazza, Angelo; De Lillo, Carlo

2017-03-01

In the last two decades, comparative research has addressed the issue of how the global and local levels of structure of visual stimuli are processed by different species, using Navon-type hierarchical figures, i.e. smaller local elements that form larger global configurations. Determining whether or not the variety of procedures adopted to test different species with hierarchical figures are equivalent is of crucial importance to ensure comparability of results. Among non-human species, global/local processing has been extensively studied in tufted capuchin monkeys using matching-to-sample tasks with hierarchical patterns. Local dominance has emerged consistently in these New World primates. In the present study, we assessed capuchins' processing of hierarchical stimuli with a method frequently adopted in studies of global/local processing in non-primate species: the conflict-choice task. Different from the matching-to-sample procedure, this task involved processing local and global information retained in long-term memory. Capuchins were trained to discriminate between consistent hierarchical stimuli (similar global and local shape) and then tested with inconsistent hierarchical stimuli (different global and local shapes). We found that capuchins preferred the hierarchical stimuli featuring the correct local elements rather than those with the correct global configuration. This finding confirms that capuchins' local dominance, typically observed using matching-to-sample procedures, is also expressed as a local preference in the conflict-choice task. Our study adds to the growing body of comparative studies on visual grouping functions by demonstrating that the methods most frequently used in the literature on global/local processing produce analogous results irrespective of extent of the involvement of memory processes.

Auditory global-local processing: effects of attention and musical experience.

PubMed

Ouimet, Tia; Foster, Nicholas E V; Hyde, Krista L

2012-10-01

In vision, global (whole) features are typically processed before local (detail) features ("global precedence effect"). However, the distinction between global and local processing is less clear in the auditory domain. The aims of the present study were to investigate: (i) the effects of directed versus divided attention, and (ii) the effect musical training on auditory global-local processing in 16 adult musicians and 16 non-musicians. Participants were presented with short nine-tone melodies, each comprised of three triplet sequences (three-tone units). In a "directed attention" task, participants were asked to focus on either the global or local pitch pattern and had to determine if the pitch pattern went up or down. In a "divided attention" task, participants judged whether the target pattern (up or down) was present or absent. Overall, global structure was perceived faster and more accurately than local structure. The global precedence effect was observed regardless of whether attention was directed to a specific level or divided between levels. Musicians performed more accurately than non-musicians overall, but non-musicians showed a more pronounced global advantage. This study provides evidence for an auditory global precedence effect across attention tasks, and for differences in auditory global-local processing associated with musical experience.

The Not-So-Global Blood Oxygen Level-Dependent Signal.

PubMed

Billings, Jacob; Keilholz, Shella

2018-04-01

Global signal regression is a controversial processing step for resting-state functional magnetic resonance imaging, partly because the source of the global blood oxygen level-dependent (BOLD) signal remains unclear. On the one hand, nuisance factors such as motion can readily introduce coherent BOLD changes across the whole brain. On the other hand, the global signal has been linked to neural activity and vigilance levels, suggesting that it contains important neurophysiological information and should not be discarded. Any widespread pattern of coordinated activity is likely to contribute appreciably to the global signal. Such patterns may include large-scale quasiperiodic spatiotemporal patterns, known also to be tied to performance on vigilance tasks. This uncertainty surrounding the separability of the global BOLD signal from concurrent neurological processes motivated an examination of the global BOLD signal's spatial distribution. The results clarify that although the global signal collects information from all tissue classes, a diverse subset of the BOLD signal's independent components contribute the most to the global signal. Further, the timing of each network's contribution to the global signal is not consistent across volunteers, confirming the independence of a constituent process that comprises the global signal.

Global Gene Expression Profiling in Omental Adipose Tissue of Morbidly Obese Diabetic African Americans.

PubMed

Doumatey, Ayo P; Xu, Huichun; Huang, Hanxia; Trivedi, Niraj S; Lei, Lin; Elkahloun, Abdel; Adeyemo, Adebowale; Rotimi, Charles N

2015-06-01

Adipose tissues play important role in the pathophysiology of obesity-related diseases including type 2 diabetes (T2D). To describe gene expression patterns and functional pathways in obesity-related T2D, we performed global transcript profiling of omental adipose tissue (OAT) in morbidly obese individuals with or without T2D. Twenty morbidly obese (mean BMI: about 54 kg/m 2 ) subjects were studied, including 14 morbidly obese individuals with T2D (cases) and 6 morbidly obese individuals without T2D (reference group). Gene expression profiling was performed using the Affymetrix U133 Plus 2.0 human genome expression array. Analysis of covariance was performed to identify differentially expressed genes (DEGs). Bioinformatics tools including PANTHER and Ingenuity Pathway Analysis (IPA) were applied to the DEGs to determine biological functions, networks and canonical pathways that were overrepresented in these individuals. At an absolute fold-change threshold of 2 and false discovery rate (FDR) < 0.05, 68 DEGs were identified in cases compared to the reference group. Myosin X (MYO10) and transforming growth factor beta regulator 1 (TBRG1) were upregulated. MYO10 encodes for an actin-based motor protein that has been associated with T2D. Telomere extension by telomerase ( HNRNPA1, TNKS2 ), D-myo-inositol (1, 4, 5)-trisphosphate biosynthesis (PIP5K1A, PIP4K2A), and regulation of actin-based motility by Rho (ARPC3) were the most significant canonical pathways and overlay with T2D signaling pathway. Upstream regulator analysis predicted 5 miRNAs (miR-320b, miR-381-3p, miR-3679-3p, miR-494-3p, and miR-141-3p,) as regulators of the expression changes identified. This study identified a number of transcripts and miRNAs in OAT as candidate novel players in the pathophysiology of T2D in African Americans.

[Neuroepigenetics: Desoxyribonucleic acid methylation in Alzheimer's disease and other dementias].

PubMed

Mendioroz Iriarte, Maite; Pulido Fontes, Laura; Méndez-López, Iván

2015-05-21

DNA methylation is an epigenetic mechanism that controls gene expression. In Alzheimer's disease (AD), global DNA hypomethylation of neurons has been described in the human cerebral cortex. Moreover, several variants in the methylation pattern of candidate genes have been identified in brain tissue when comparing AD patients and controls. Specifically, DNA methylation changes have been observed in PSEN1 and APOE, both genes previously being involved in the pathophysiology of AD. In other degenerative dementias, methylation variants have also been described in key genes, such as hypomethylation of the SNCA gene in Parkinson's disease and dementia with Lewy bodies or hypermethylation of the GRN gene promoter in frontotemporal dementia. The finding of aberrant DNA methylation patterns shared by brain tissue and peripheral blood opens the door to use those variants as epigenetic biomarkers in the diagnosis of neurodegenerative diseases. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Idealized model of polar cap currents, fields, and auroras

NASA Technical Reports Server (NTRS)

Cornwall, J. M.

1985-01-01

During periods of northward Bz, the electric field applied to the magnetosphere is generally opposite to that occurring during southward Bz and complicated patterns of convection result, showing some features reversed in comparison with the southward Bz case. A study is conducted of a simple generalization of early work on idealized convection models, which allows for coexistence of sunward convection over the central polar cap and antisunward convection elsewhere in the cap. The present model, valid for By approximately 0, has a four-cell convection pattern and is based on the combination of ionospheric current conservation with a relation between parallel auroral currents and parallel potential drops. Global magnetospheric issues involving, e.g., reconnection are not considered. The central result of this paper is an expression giving the parallel potential drop for polar cap auroras (with By approximately 0) in terms of the polar cap convection field profile.

Improved water quality can ameliorate effects of climate change on corals.

PubMed

Wooldridge, Scott A; Done, Terence J

2009-09-01

The threats of wide-scale coral bleaching and reef demise associated with anthropogenic climate change are widely known. Moreover, rates of genetic adaptation and/or changes in the coral-zooxanthella partnerships are considered unlikely to be sufficiently fast for corals to acquire increased physiological resistance to increasing sea temperatures and declining pH. However, it has been suggested that coral reef resilience to climate change may be improved by good local management of coral reefs, including management of water quality. Here, using major data sets from the Great Barrier Reef (GBR), Australia, we investigate geographic patterns of coral bleaching in 1998 and 2002 and outline a synergism between heat stress and nutrient flux as a major causative mechanism for those patterns. The study provides the first concrete evidence for the oft-expressed belief that improved coral reef management will increase the regional-scale survival prospects of coral reefs to global climate change.

Similar Response Patterns to 5%Topical Minoxidil Foam in Frontal and Vertex Scalp of Men with Androgenetic Alopecia: A Microarray Analysis

PubMed Central

Mirmirani, P.; Consolo, M.; Oyetakin-White, P.; Baron, E.; Leahy, P.; Karnik, P.

2014-01-01

Summary Background There are regional variations in scalp hair miniaturization seen in androgenetic alopecia (AGA). Use of topical minoxidil can lead to reversal of miniaturization in the vertex scalp. However, its effects on other scalp regions are less well studied. Methods A placebo controlled double-blinded prospective pilot study of minoxidil topical foam 5% (MTF) vs placebo was conducted in sixteen healthy men ages 18-49 with Hamilton-Norwood type IV-V thinning. The subjects were asked to apply the treatment (active drug or placebo) to the scalp twice daily for eight weeks. Stereotactic scalp photographs were taken at the baseline and final visits to monitor global hair growth. Scalp biopsies were done at the leading edge of hair loss from the frontal and vertex scalp before and after treatment with MTF and placebo and microarray analysis was done using the Affymetrix GeneChip HG U133 Plus 2.0. Results Global stereotactic photographs showed that MTF induced hair growth in both the frontal and vertex scalp of AGA patients. Regional differences in gene expression profiles were observed before treatment. However, MTF treatment induced the expression of hair keratin associated genes and decreased the expression of epidermal differentiation complex (EDC) and inflammatory genes in both scalp regions. Conclusions These data suggest that MTF is effective in the treatment of both the frontal and vertex scalp of AGA patients. PMID:25204361

iTRAQ-Based Quantitative Proteomic Analysis of the Initiation of Head Regeneration in Planarians.

PubMed

Geng, Xiaofang; Wang, Gaiping; Qin, Yanli; Zang, Xiayan; Li, Pengfei; Geng, Zhi; Xue, Deming; Dong, Zimei; Ma, Kexue; Chen, Guangwen; Xu, Cunshuan

2015-01-01

The planarian Dugesia japonica has amazing ability to regenerate a head from the anterior ends of the amputated stump with maintenance of the original anterior-posterior polarity. Although planarians present an attractive system for molecular investigation of regeneration and research has focused on clarifying the molecular mechanism of regeneration initiation in planarians at transcriptional level, but the initiation mechanism of planarian head regeneration (PHR) remains unclear at the protein level. Here, a global analysis of proteome dynamics during the early stage of PHR was performed using isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics strategy, and our data are available via ProteomeXchange with identifier PXD002100. The results showed that 162 proteins were differentially expressed at 2 h and 6 h following amputation. Furthermore, the analysis of expression patterns and functional enrichment of the differentially expressed proteins showed that proteins involved in muscle contraction, oxidation reduction and protein synthesis were up-regulated in the initiation of PHR. Moreover, ingenuity pathway analysis showed that predominant signaling pathways such as ILK, calcium, EIF2 and mTOR signaling which were associated with cell migration, cell proliferation and protein synthesis were likely to be involved in the initiation of PHR. The results for the first time demonstrated that muscle contraction and ILK signaling might played important roles in the initiation of PHR at the global protein level. The findings of this research provide a molecular basis for further unraveling the mechanism of head regeneration initiation in planarians.

Global transcriptome analysis of the maize (Zea mays L.) inbred line 08LF during leaf senescence initiated by pollination-prevention

PubMed Central

Wang, Shunxi; Wu, Liuji; Ku, Lixia; Zhang, Jun; Song, Xiaoheng; Liu, Haiping

2017-01-01

In maize (Zea mays), leaf senescence acts as a nutrient recycling process involved in proteins, lipids, and nucleic acids degradation and transport to the developing sink. However, the molecular mechanisms of pre-maturation associated with pollination-prevention remain unclear in maize. To explore global gene expression changes during the onset and progression of senescence in maize, the inbred line 08LF, with severe early senescence caused by pollination prevention, was selected. Phenotypic observation showed that the onset of leaf senescence of 08LF plants occurred approximately 14 days after silking (DAS) by pollination prevention. Transcriptional profiling analysis of the leaf at six developmental stages during induced senescence revealed that a total of 5,432 differentially expressed genes (DEGs) were identified, including 2314 up-regulated genes and 1925 down-regulated genes. Functional annotation showed that the up-regulated genes were mainly enriched in multi-organism process and nitrogen compound transport, whereas down-regulated genes were involved in photosynthesis. Expression patterns and pathway enrichment analyses of early-senescence related genes indicated that these DEGs are involved in complex regulatory networks, especially in the jasmonic acid pathway. In addition, transcription factors from several families were detected, particularly the CO-like, NAC, ERF, GRAS, WRKY and ZF-HD families, suggesting that these transcription factors might play important roles in driving leaf senescence in maize as a result of pollination-prevention. PMID:28973044

Sampling Capacity Underlies Individual Differences in Human Associative Learning

PubMed Central

2014-01-01

Though much work has studied how external factors, such as stimulus properties, influence generalization of associative strength, there has been limited exploration of the influence that internal dispositions may contribute to stimulus processing. Here we report 2 studies using a modified negative patterning discrimination to test the relationship between global processing and generalization. Global processing was associated with stronger negative patterning discrimination, indicative of limited generalization between distinct stimulus compounds and their constituent elements. In Experiment 2, participants pretrained to adopt global processing similarly showed strong negative patterning discrimination. These results demonstrate considerable individual difference in capacity to engage in negative patterning discrimination and suggest that the tendency toward global processing may be one factor explaining this variability. The need for models of learning to account for this variability in learning is discussed. PMID:24446699

Global circulation patterns of seasonal influenza viruses vary with antigenic drift

PubMed Central

Bedford, Trevor; Riley, Steven; Barr, Ian G.; Broor, Shobha; Chadha, Mandeep; Cox, Nancy J.; Daniels, Rodney S.; Gunasekaran, C. Palani; Hurt, Aeron C.; Kelso, Anne; Lewis, Nicola S.; Li, Xiyan; McCauley, John W.; Odagiri, Takato; Potdar, Varsha; Rambaut, Andrew; Shu, Yuelong; Skepner, Eugene; Smith, Derek J.; Suchard, Marc A.; Tashiro, Masato; Wang, Dayan; Xu, Xiyan; Lemey, Philippe; Russell, Colin A.

2015-01-01

Understanding the spatio-temporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well-characterized1-7 but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here, based on analyses of 9,604 hemagglutinin sequences of human seasonal influenza viruses from 2000–2012, we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses. While genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast (E-SE) Asia, genetic variants of A/H1N1 and B viruses persisted across multiple seasons and exhibited complex global dynamics with E-SE Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as likely drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology and human behavior. PMID:26053121

Global circulation patterns of seasonal influenza viruses vary with antigenic drift

NASA Astrophysics Data System (ADS)

Bedford, Trevor; Riley, Steven; Barr, Ian G.; Broor, Shobha; Chadha, Mandeep; Cox, Nancy J.; Daniels, Rodney S.; Gunasekaran, C. Palani; Hurt, Aeron C.; Kelso, Anne; Klimov, Alexander; Lewis, Nicola S.; Li, Xiyan; McCauley, John W.; Odagiri, Takato; Potdar, Varsha; Rambaut, Andrew; Shu, Yuelong; Skepner, Eugene; Smith, Derek J.; Suchard, Marc A.; Tashiro, Masato; Wang, Dayan; Xu, Xiyan; Lemey, Philippe; Russell, Colin A.

2015-07-01

Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well characterized, but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.

Cytomegalovirus shapes long-term immune reconstitution after allogeneic stem cell transplantation

PubMed Central

Itzykson, Raphael; Robin, Marie; Moins-Teisserenc, Helene; Delord, Marc; Busson, Marc; Xhaard, Aliénor; de Fontebrune, Flore Sicre; de Latour, Régis Peffault; Toubert, Antoine; Socié, Gérard

2015-01-01

Immune reconstitution after allogeneic stem cell transplantation is a dynamic and complex process depending on the recipient and donor characteristics, on the modalities of transplantation, and on the occurrence of graft-versus-host disease. Multivariate methods widely used for gene expression profiling can simultaneously analyze the patterns of a great number of biological variables on a heterogeneous set of patients. Here we use these methods on flow cytometry assessment of up to 25 lymphocyte populations to analyze the global pattern of long-term immune reconstitution after transplantation. Immune patterns were most distinct from healthy controls at six months, and had not yet fully recovered as long as two years after transplant. The two principal determinants of variability were linked to the balance of B and CD8+ T cells and of natural killer and B cells, respectively. Recipient’s cytomegalovirus serostatus, cytomegalovirus replication, and chronic graft-versus-host disease were the main factors shaping the immune pattern one year after transplant. We identified a complex signature of under- and over-representation of immune populations dictated by recipient’s cytomegalovirus seropositivity. Finally, we identified dimensions of variance in immune patterns as significant predictors of long-term non-relapse mortality, independently of chronic graft-versus-host disease. PMID:25261095

Global Patterns of Tectonism on Titan from Mountain Chains and Virgae

NASA Technical Reports Server (NTRS)

Cook, C.; Barnes, J. W.; Radebaugh, J.; Hurford, T.; Ktatenhorn, S. A.

2012-01-01

This research is based on the exploration of tectonic patterns on Titan from a global perspective. Several moons in the outer solar system display patterns of surface tectonic features that imply global stress fields driven or modified by global forces. Patterns such as these are seen in Europa's tidally induced fracture patterns, Enceladus's tiger stripes, and Ganymede's global expansion induced normal fault bands. Given its proximity to Saturn, as well as its eccentric orbit, tectonic features and global stresses may be present on Titan as well. Titan displays possible tectonic structures, such as mountain chains along its equator (Radebaugh et al. 2007), as well as the unexplored dark linear streaks termed virgae by the IAU. Imaged by Cassini with the RADAR instrument, mountain chains near the equator are observed with a predominante east-west orientation (Liu et al. 2012, Mitri et al. 2010). Orientations such as these can be explained by modifications in the global tidal stress field induced by global contraction followed by rotational spin-up. Also, due to Titan's eccentric orbit, its current rotation rate may be in an equilibrium between tidal spin-up near periapsis and spin-down near apoapsis (Barnes and Fortney 2003). Additional stress from rotational spin-up provides an asymmetry to the stress field. This, combined with an isotropic stress from radial contraction, favors the formation of equatorial mountain chains in an east-west direction. The virgae, which have been imaged by Cassini with both the Visual and Infrared Mapping Spectrometer (VIMS) and Imaging Science Subsystem (ISS) instruments, are located predominately near 30 degrees latitude in either hemisphere. Oriented with a pronounced elongation in the east-west direction, all observed virgae display similar characteristics: similar relative albedos as the surrounding terrain however darkened with an apparent neutral absorber, broken-linear or rounded sharp edges, and connected, angular elements with distinct, linear edges. Virgae imaged during northern latitude passes are oriented with their long dimensions toward Titan's antiSaturn point. If the virgae are of tectonic origin, for instance if the turn out to be i.e. grabens, they could serve as markers to Titan's global stress field. Using them in this way allows for a mapping of global tectonic patterns. These patterns will be tested for consistency against the various sources of global stress and orientations of mountain chains. By determining what drives Titan's tectonics globally, we will be able to place Titan within the context of the other outer planet icy satellites.

REGIONAL AND GLOBAL PATTERNS OF POPULATION, LAND USE AND LAND COVER CHANGE: AN OVERVIEW OF STRESSORS AND IMPACTS

EPA Science Inventory

This paper provides an overview of land use and land cover (LULC) change and regional to global patterns of that change and responses. Human activities now dominate the Earth's global ecosystem and LULC change is one of the most pervasive and influential activities. LULC change a...

Optogenetic Activation of the Sensorimotor Cortex Reveals "Local Inhibitory and Global Excitatory" Inputs to the Basal Ganglia.

PubMed

Ozaki, Mitsunori; Sano, Hiromi; Sato, Shigeki; Ogura, Mitsuhiro; Mushiake, Hajime; Chiken, Satomi; Nakao, Naoyuki; Nambu, Atsushi

2017-12-01

To understand how information from different cortical areas is integrated and processed through the cortico-basal ganglia pathways, we used optogenetics to systematically stimulate the sensorimotor cortex and examined basal ganglia activity. We utilized Thy1-ChR2-YFP transgenic mice, in which channelrhodopsin 2 is robustly expressed in layer V pyramidal neurons. We applied light spots to the sensorimotor cortex in a grid pattern and examined neuronal responses in the globus pallidus (GP) and entopeduncular nucleus (EPN), which are the relay and output nuclei of the basal ganglia, respectively. Light stimulation typically induced a triphasic response composed of early excitation, inhibition, and late excitation in GP/EPN neurons. Other response patterns lacking 1 or 2 of the components were also observed. The distribution of the cortical sites whose stimulation induced a triphasic response was confined, whereas stimulation of the large surrounding areas induced early and late excitation without inhibition. Our results suggest that cortical inputs to the GP/EPN are organized in a "local inhibitory and global excitatory" manner. Such organization seems to be the neuronal basis for information processing through the cortico-basal ganglia pathways, that is, releasing and terminating necessary information at an appropriate timing, while simultaneously suppressing other unnecessary information. © The Author 2017. Published by Oxford University Press.

Transcriptome-wide analysis of alternative RNA splicing events in Epstein-Barr virus-associated gastric carcinomas

PubMed Central

Armero, Victoria E. S.; Tremblay, Marie-Pier; Allaire, Andréa; Boudreault, Simon; Martenon-Brodeur, Camille; Duval, Cyntia; Durand, Mathieu; Lapointe, Elvy; Thibault, Philippe; Tremblay-Létourneau, Maude; Perreault, Jean-Pierre; Scott, Michelle S.

2017-01-01

Multiple human diseases including cancer have been associated with a dysregulation in RNA splicing patterns. In the current study, modifications to the global RNA splicing landscape of cellular genes were investigated in the context of Epstein-Barr virus-associated gastric cancer. Global alterations to the RNA splicing landscape of cellular genes was examined in a large-scale screen from 295 primary gastric adenocarcinomas using high-throughput RNA sequencing data. RT-PCR analysis, mass spectrometry, and co-immunoprecipitation studies were also used to experimentally validate and investigate the differential alternative splicing (AS) events that were observed through RNA-seq studies. Our study identifies alterations in the AS patterns of approximately 900 genes such as tumor suppressor genes, transcription factors, splicing factors, and kinases. These findings allowed the identification of unique gene signatures for which AS is misregulated in both Epstein-Barr virus-associated gastric cancer and EBV-negative gastric cancer. Moreover, we show that the expression of Epstein–Barr nuclear antigen 1 (EBNA1) leads to modifications in the AS profile of cellular genes and that the EBNA1 protein interacts with cellular splicing factors. These findings provide insights into the molecular differences between various types of gastric cancer and suggest a role for the EBNA1 protein in the dysregulation of cellular AS. PMID:28493890

Transcriptome-wide analysis of alternative RNA splicing events in Epstein-Barr virus-associated gastric carcinomas.

PubMed

Armero, Victoria E S; Tremblay, Marie-Pier; Allaire, Andréa; Boudreault, Simon; Martenon-Brodeur, Camille; Duval, Cyntia; Durand, Mathieu; Lapointe, Elvy; Thibault, Philippe; Tremblay-Létourneau, Maude; Perreault, Jean-Pierre; Scott, Michelle S; Bisaillon, Martin

2017-01-01

Multiple human diseases including cancer have been associated with a dysregulation in RNA splicing patterns. In the current study, modifications to the global RNA splicing landscape of cellular genes were investigated in the context of Epstein-Barr virus-associated gastric cancer. Global alterations to the RNA splicing landscape of cellular genes was examined in a large-scale screen from 295 primary gastric adenocarcinomas using high-throughput RNA sequencing data. RT-PCR analysis, mass spectrometry, and co-immunoprecipitation studies were also used to experimentally validate and investigate the differential alternative splicing (AS) events that were observed through RNA-seq studies. Our study identifies alterations in the AS patterns of approximately 900 genes such as tumor suppressor genes, transcription factors, splicing factors, and kinases. These findings allowed the identification of unique gene signatures for which AS is misregulated in both Epstein-Barr virus-associated gastric cancer and EBV-negative gastric cancer. Moreover, we show that the expression of Epstein-Barr nuclear antigen 1 (EBNA1) leads to modifications in the AS profile of cellular genes and that the EBNA1 protein interacts with cellular splicing factors. These findings provide insights into the molecular differences between various types of gastric cancer and suggest a role for the EBNA1 protein in the dysregulation of cellular AS.

Isoform-level gene expression patterns in single-cell RNA-sequencing data.

PubMed

Vu, Trung Nghia; Wills, Quin F; Kalari, Krishna R; Niu, Nifang; Wang, Liewei; Pawitan, Yudi; Rantalainen, Mattias

2018-02-27

RNA sequencing of single cells enables characterization of transcriptional heterogeneity in seemingly homogeneous cell populations. Single-cell sequencing has been applied in a wide range of researches fields. However, few studies have focus on characterization of isoform-level expression patterns at the single-cell level. In this study we propose and apply a novel method, ISOform-Patterns (ISOP), based on mixture modeling, to characterize the expression patterns of isoform pairs from the same gene in single-cell isoform-level expression data. We define six principal patterns of isoform expression relationships and describe a method for differential-pattern analysis. We demonstrate ISOP through analysis of single-cell RNA-sequencing data from a breast cancer cell line, with replication in three independent datasets. We assigned the pattern types to each of 16,562 isoform-pairs from 4,929 genes. Among those, 26% of the discovered patterns were significant (p<0.05), while remaining patterns are possibly effects of transcriptional bursting, drop-out and stochastic biological heterogeneity. Furthermore, 32% of genes discovered through differential-pattern analysis were not detected by differential-expression analysis. The effect of drop-out events, mean expression level, and properties of the expression distribution on the performances of ISOP were also investigated through simulated datasets. To conclude, ISOP provides a novel approach for characterization of isoformlevel preference, commitment and heterogeneity in single-cell RNA-sequencing data. The ISOP method has been implemented as a R package and is available at https://github.com/nghiavtr/ISOP under a GPL-3 license. mattias.rantalainen@ki.se. Supplementary data are available at Bioinformatics online.

FoxP2 expression in the cerebellum and inferior olive: development of the transverse stripe-shaped expression pattern in the mouse cerebellar cortex.

PubMed

Fujita, Hirofumi; Sugihara, Izumi

2012-02-15

Many molecules are expressed heterogeneously in subpopulations of cerebellar Purkinje cells (PCs) and inferior olive (IO) neurons during development or in adulthood. These expression patterns are often organized in longitudinal stripes in the cerebellar cortex, which may be related to functional compartmentalization. FoxP2, a transcription factor, is expressed in PCs and IO neurons, but the details of its expression pattern remain unclear. Here we examined FoxP2 expression patterns systematically by immunostaining serial sections of the hindbrain from embryonic day 14.5 to adulthood in mice. FoxP2 was highly expressed in virtually all PCs at and before postnatal day 6 (P6), except for those in the flocculus and small parts of the nodulus (vermal lobule X), where FoxP2 expression was moderate or absent. After P6, FoxP2 expression gradually diminished in PCs in some areas. In adults, FoxP2 was expressed, less intensely than in earlier stages, in subsets of PCs that were mostly arranged transversely along the folial apices. In contrast, FoxP2 was expressed intensely in most IO neurons during development and in adulthood. FoxP2 was also expressed in a small population of neurons in the cerebellar nuclei. FoxP2 expression in adult rats and chicks was generally comparable to that in adult mice, suggesting evolutionary conservation of the expression pattern. Thus, the FoxP2 expression pattern reflects new transverse compartmentalization in the adult cerebellar cortex, although its functional significance remains unclear. Copyright © 2011 Wiley-Liss, Inc.

Epigenetic and Epitranscriptomic Factors Make a Mark on Hematopoietic Stem Cell Development.

PubMed

Kasper, Dionna M; Nicoli, Stefania

2018-03-01

Blood specification is a highly dynamic process, whereby committed hemogenic endothelial cells (ECs) progressively transdifferentiate into multipotent, self-renewing hematopoietic stem cells (HSCs). Massive changes in gene expression must occur to switch cell identity, however the factors that mediate such an effect were a mystery until recently. This review summarizes the higher-order mechanisms involved in endothelial to hematopoietic reprogramming identified thus far. Accumulating evidence from mouse and zebrafish studies reveal that numerous chromatin-modifying (epigenetic) and RNA-modifying (epitranscriptomic) factors are required for the formation of HSCs from hemogenic endothelium. These genes function throughout the endothelial-hematopoietic transition, suggesting a dynamic interplay between 'epi'-machineries. Epigenetic and epitranscriptomic regulation are key mechanisms for reshaping global EC gene expression patterns to those that support HSC production. Future studies that capture modification dynamics should bring us closer to a complete understanding of how HSCs transition from hemogenic endothelium at the molecular level.

Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity.

PubMed

Ma, Siming; Upneja, Akhil; Galecki, Andrzej; Tsai, Yi-Miau; Burant, Charles F; Raskind, Sasha; Zhang, Quanwei; Zhang, Zhengdong D; Seluanov, Andrei; Gorbunova, Vera; Clish, Clary B; Miller, Richard A; Gladyshev, Vadim N

2016-11-22

Mammalian lifespan differs by >100 fold, but the mechanisms associated with such longevity differences are not understood. Here, we conducted a study on primary skin fibroblasts isolated from 16 species of mammals and maintained under identical cell culture conditions. We developed a pipeline for obtaining species-specific ortholog sequences, profiled gene expression by RNA-seq and small molecules by metabolite profiling, and identified genes and metabolites correlating with species longevity. Cells from longer lived species up-regulated genes involved in DNA repair and glucose metabolism, down-regulated proteolysis and protein transport, and showed high levels of amino acids but low levels of lysophosphatidylcholine and lysophosphatidylethanolamine. The amino acid patterns were recapitulated by further analyses of primate and bird fibroblasts. The study suggests that fibroblast profiling captures differences in longevity across mammals at the level of global gene expression and metabolite levels and reveals pathways that define these differences.

Global analysis of gene expression in mineralizing fish vertebra-derived cell lines: new insights into anti-mineralogenic effect of vanadate

PubMed Central

2011-01-01

Background Fish has been deemed suitable to study the complex mechanisms of vertebrate skeletogenesis and gilthead seabream (Sparus aurata), a marine teleost with acellular bone, has been successfully used in recent years to study the function and regulation of bone and cartilage related genes during development and in adult animals. Tools recently developed for gilthead seabream, e.g. mineralogenic cell lines and a 4 × 44K Agilent oligo-array, were used to identify molecular determinants of in vitro mineralization and genes involved in anti-mineralogenic action of vanadate. Results Global analysis of gene expression identified 4,223 and 4,147 genes differentially expressed (fold change - FC > 1.5) during in vitro mineralization of VSa13 (pre-chondrocyte) and VSa16 (pre-osteoblast) cells, respectively. Comparative analysis indicated that nearly 45% of these genes are common to both cell lines and gene ontology (GO) classification is also similar for both cell types. Up-regulated genes (FC > 10) were mainly associated with transport, matrix/membrane, metabolism and signaling, while down-regulated genes were mainly associated with metabolism, calcium binding, transport and signaling. Analysis of gene expression in proliferative and mineralizing cells exposed to vanadate revealed 1,779 and 1,136 differentially expressed genes, respectively. Of these genes, 67 exhibited reverse patterns of expression upon vanadate treatment during proliferation or mineralization. Conclusions Comparative analysis of expression data from fish and data available in the literature for mammalian cell systems (bone-derived cells undergoing differentiation) indicate that the same type of genes, and in some cases the same orthologs, are involved in mechanisms of in vitro mineralization, suggesting their conservation throughout vertebrate evolution and across cell types. Array technology also allowed identification of genes differentially expressed upon exposure of fish cell lines to vanadate and likely involved in its anti-mineralogenic activity. Many were found to be unknown or they were never associated to bone homeostasis previously, thus providing a set of potential candidates whose study will likely bring insights into the complex mechanisms of tissue mineralization and bone formation. PMID:21668972

Attribution of Large-Scale Climate Patterns to Seasonal Peak-Flow and Prospects for Prediction Globally

NASA Astrophysics Data System (ADS)

Lee, Donghoon; Ward, Philip; Block, Paul

2018-02-01

Flood-related fatalities and impacts on society surpass those from all other natural disasters globally. While the inclusion of large-scale climate drivers in streamflow (or high-flow) prediction has been widely studied, an explicit link to global-scale long-lead prediction is lacking, which can lead to an improved understanding of potential flood propensity. Here we attribute seasonal peak-flow to large-scale climate patterns, including the El Niño Southern Oscillation (ENSO), Pacific Decadal Oscillation (PDO), North Atlantic Oscillation (NAO), and Atlantic Multidecadal Oscillation (AMO), using streamflow station observations and simulations from PCR-GLOBWB, a global-scale hydrologic model. Statistically significantly correlated climate patterns and streamflow autocorrelation are subsequently applied as predictors to build a global-scale season-ahead prediction model, with prediction performance evaluated by the mean squared error skill score (MSESS) and the categorical Gerrity skill score (GSS). Globally, fair-to-good prediction skill (20% ≤ MSESS and 0.2 ≤ GSS) is evident for a number of locations (28% of stations and 29% of land area), most notably in data-poor regions (e.g., West and Central Africa). The persistence of such relevant climate patterns can improve understanding of the propensity for floods at the seasonal scale. The prediction approach developed here lays the groundwork for further improving local-scale seasonal peak-flow prediction by identifying relevant global-scale climate patterns. This is especially attractive for regions with limited observations and or little capacity to develop flood early warning systems.

Global vegetation productivity response to climatic oscillations during the satellite era.

PubMed

Gonsamo, Alemu; Chen, Jing M; Lombardozzi, Danica

2016-10-01

Climate control on global vegetation productivity patterns has intensified in response to recent global warming. Yet, the contributions of the leading internal climatic variations to global vegetation productivity are poorly understood. Here, we use 30 years of global satellite observations to study climatic variations controls on continental and global vegetation productivity patterns. El Niño-Southern Oscillation (ENSO) phases (La Niña, neutral, and El Niño years) appear to be a weaker control on global-scale vegetation productivity than previously thought, although continental-scale responses are substantial. There is also clear evidence that other non-ENSO climatic variations have a strong control on spatial patterns of vegetation productivity mainly through their influence on temperature. Among the eight leading internal climatic variations, the East Atlantic/West Russia Pattern extensively controls the ensuing year vegetation productivity of the most productive tropical and temperate forest ecosystems of the Earth's vegetated surface through directionally consistent influence on vegetation greenness. The Community Climate System Model (CCSM4) simulations do not capture the observed patterns of vegetation productivity responses to internal climatic variations. Our analyses show the ubiquitous control of climatic variations on vegetation productivity and can further guide CCSM and other Earth system models developments to represent vegetation response patterns to unforced variability. Several winter time internal climatic variation indices show strong potentials on predicting growing season vegetation productivity two to six seasons ahead which enables national governments and farmers forecast crop yield to ensure supplies of affordable food, famine early warning, and plan management options to minimize yield losses ahead of time. © 2016 John Wiley & Sons Ltd.

Spatial correlations of interdecadal variation in global surface temperatures

NASA Technical Reports Server (NTRS)

Mann, Michael E.; Park, Jeffrey

1993-01-01

We have analyzed spatial correlation patterns of interdecadal global surface temperature variability from an empirical perspective. Using multitaper coherence estimates from 140-yr records, we find that correlations between hemispheres are significant at about 95 percent confidence for nonrandomness for most of the frequency band in the 0.06-0.24 cyc/yr range. Coherence estimates of pairs of 100-yr grid-point temperature data series near 5-yr period reveal teleconnection patterns consistent with known patterns of ENSO variability. Significant correlated variability is observed near 15 year period, with the dominant teleconnection pattern largely confined to the Northern Hemisphere. Peak-to-peak Delta-T is at about 0.5 deg, with simultaneous warming and cooling of discrete patches on the earth's surface. A global average of this pattern would largely cancel.

Gene expression underlying adaptive variation in Heliconius wing patterns: non-modular regulation of overlapping cinnabar and vermilion prepatterns.

PubMed

Reed, Robert D; McMillan, W Owen; Nagy, Lisa M

2008-01-07

Geographical variation in the mimetic wing patterns of the butterfly Heliconius erato is a textbook example of adaptive polymorphism; however, little is known about how this variation is controlled developmentally. Using microarrays and qPCR, we identified and compared expression of candidate genes potentially involved with a red/yellow forewing band polymorphism in H. erato. We found that transcripts encoding the pigment synthesis enzymes cinnabar and vermilion showed pattern- and polymorphism-related expression patterns, respectively. cinnabar expression was associated with the forewing band regardless of pigment colour, providing the first gene expression pattern known to be correlated with a major Heliconius colour pattern. In contrast, vermilion expression changed spatially over time in red-banded butterflies, but was not expressed at detectable levels in yellow-banded butterflies, suggesting that regulation of this gene may be involved with the red/yellow polymorphism. Furthermore, we found that the yellow pigment, 3-hydroxykynurenine, is incorporated into wing scales from the haemolymph rather than being synthesized in situ. We propose that some aspects of Heliconius colour patterns are determined by spatio-temporal overlap of pigment gene transcription prepatterns and speculate that evolutionary changes in vermilion regulation may in part underlie an adaptive colour pattern polymorphism.

Spatiotemporal differences in the c-fos pathway between C57BL/6J and DBA/2J mice following flurothyl-induced seizures: a dissociation of hippocampal Fos from seizure activity

PubMed Central

Kadiyala, Sridhar B.; Papandrea, Dominick; Tuz, Karina; Anderson, Tara M.; Jayakumar, Sachidhanand; Herron, Bruce J.; Ferland, Russell J.

2014-01-01

Significant differences in seizure characteristics between inbred mouse strains highlight the importance of genetic predisposition to epilepsy. Here, we examined the genetic differences between the seizure-resistant C57BL/6J (B6) mouse strain and the seizure-susceptible DBA/2J (D2) strain in the phospho-Erk and Fos pathways to examine seizure-induced neuronal activity to uncover potential mechanistic correlates to these disparate seizure responsivities. Expression of neural activity markers was examined following 1, 5, or 8 seizures, or after 8 seizures, a 28 day rest period, and a final flurothyl rechallenge. Two brain regions, the hippocampus and ventromedial nucleus of the hypothalamus (VMH), had significantly different Fos expression profiles following seizures. Fos expression was highly robust in B6 hippocampus following one seizure and remained elevated following multiple seizures. Conversely, there was an absence of Fos (and phospho-Erk) expression in D2 hippocampus following one generalized seizure that increased with multiple seizures. This lack of Fos expression occurred despite intracranial electroencephalographic recordings indicating that the D2 hippocampus propagated ictal discharge during the first flurothyl seizure suggesting a dissociation of seizure discharge from Fos and phospho-Erk expression. Global transcriptional analysis confirmed a dysregulation of the c-fos pathway in D2 mice following 1 seizure. Moreover, global analysis of RNA expression differences between B6 and D2 hippocampus revealed a unique pattern of transcripts that were co-regulated with Fos in D2 hippocampus following 1 seizure. These expression differences could, in part, account for D2’s seizure susceptibility phenotype. Following 8 seizures, a 28 day rest period, and a final flurothyl rechallenge, ~85% of B6 mice develop a more complex seizure phenotype consisting of a clonic-forebrain seizure that uninterruptedly progresses into a brainstem seizure. This seizure phenotype in B6 mice is highly correlated with bilateral Fos expression in the VMH and was not observed in D2 mice, which always express clonic-forebrain seizures upon flurothyl retest. Overall, these results illustrate specific differences in protein and RNA expression in different inbred strains following seizures that precede the reorganizational events that affect seizure susceptibility and changes in seizure semiology over time. PMID:25524858

Spatiotemporal differences in the c-fos pathway between C57BL/6J and DBA/2J mice following flurothyl-induced seizures: A dissociation of hippocampal Fos from seizure activity.

PubMed

Kadiyala, Sridhar B; Papandrea, Dominick; Tuz, Karina; Anderson, Tara M; Jayakumar, Sachidhanand; Herron, Bruce J; Ferland, Russell J

2015-01-01

Significant differences in seizure characteristics between inbred mouse strains highlight the importance of genetic predisposition to epilepsy. Here, we examined the genetic differences between the seizure-resistant C57BL/6J (B6) mouse strain and the seizure-susceptible DBA/2J (D2) strain in the phospho-Erk and Fos pathways to examine seizure-induced neuronal activity to uncover potential mechanistic correlates to these disparate seizure responsivities. Expression of neural activity markers was examined following 1, 5, or 8 seizures, or after 8 seizures, a 28 day rest period, and a final flurothyl rechallenge. Two brain regions, the hippocampus and ventromedial nucleus of the hypothalamus (VMH), had significantly different Fos expression profiles following seizures. Fos expression was highly robust in B6 hippocampus following one seizure and remained elevated following multiple seizures. Conversely, there was an absence of Fos (and phospho-Erk) expression in D2 hippocampus following one generalized seizure that increased with multiple seizures. This lack of Fos expression occurred despite intracranial electroencephalographic recordings indicating that the D2 hippocampus propagated ictal discharge during the first flurothyl seizure suggesting a dissociation of seizure discharge from Fos and phospho-Erk expression. Global transcriptional analysis confirmed a dysregulation of the c-fos pathway in D2 mice following 1 seizure. Moreover, global analysis of RNA expression differences between B6 and D2 hippocampus revealed a unique pattern of transcripts that were co-regulated with Fos in D2 hippocampus following 1 seizure. These expression differences could, in part, account for D2's seizure susceptibility phenotype. Following 8 seizures, a 28 day rest period, and a final flurothyl rechallenge, ∼85% of B6 mice develop a more complex seizure phenotype consisting of a clonic-forebrain seizure that uninterruptedly progresses into a brainstem seizure. This seizure phenotype in B6 mice is highly correlated with bilateral Fos expression in the VMH and was not observed in D2 mice, which always express clonic-forebrain seizures upon flurothyl retest. Overall, these results illustrate specific differences in protein and RNA expression in different inbred strains following seizures that precede the reorganizational events that affect seizure susceptibility and changes in seizure semiology over time. Copyright © 2014 Elsevier B.V. All rights reserved.

Chromatin organization and global regulation of Hox gene clusters

PubMed Central

Montavon, Thomas; Duboule, Denis

2013-01-01

During development, a properly coordinated expression of Hox genes, within their different genomic clusters is critical for patterning the body plans of many animals with a bilateral symmetry. The fascinating correspondence between the topological organization of Hox clusters and their transcriptional activation in space and time has served as a paradigm for understanding the relationships between genome structure and function. Here, we review some recent observations, which revealed highly dynamic changes in the structure of chromatin at Hox clusters, in parallel with their activation during embryonic development. We discuss the relevance of these findings for our understanding of large-scale gene regulation. PMID:23650639

GEsture: an online hand-drawing tool for gene expression pattern search.

PubMed

Wang, Chunyan; Xu, Yiqing; Wang, Xuelin; Zhang, Li; Wei, Suyun; Ye, Qiaolin; Zhu, Youxiang; Yin, Hengfu; Nainwal, Manoj; Tanon-Reyes, Luis; Cheng, Feng; Yin, Tongming; Ye, Ning

2018-01-01

Gene expression profiling data provide useful information for the investigation of biological function and process. However, identifying a specific expression pattern from extensive time series gene expression data is not an easy task. Clustering, a popular method, is often used to classify similar expression genes, however, genes with a 'desirable' or 'user-defined' pattern cannot be efficiently detected by clustering methods. To address these limitations, we developed an online tool called GEsture. Users can draw, or graph a curve using a mouse instead of inputting abstract parameters of clustering methods. GEsture explores genes showing similar, opposite and time-delay expression patterns with a gene expression curve as input from time series datasets. We presented three examples that illustrate the capacity of GEsture in gene hunting while following users' requirements. GEsture also provides visualization tools (such as expression pattern figure, heat map and correlation network) to display the searching results. The result outputs may provide useful information for researchers to understand the targets, function and biological processes of the involved genes.

Assessing global radiative forcing due to regional emissions of tropospheric ozone precursors: a step towards climate credit for ozone reductions

NASA Astrophysics Data System (ADS)

Mauzerall, D. L.; Naik, V.; Horowitz, L. W.; Schwarzkopf, D.; Ramaswamy, V.; Oppenheimer, M.

2005-05-01

Carbon dioxide emissions from fossil-fuel consumption are presented for the five Asian countries that are among the global leaders in anthropogenic carbon emissions: China (13% of global total), Japan (5% of global total), India (5% of global total), South Korea (2% of global total), and Indonesia (1% of global total). Together, these five countries represent over a quarter of the world's fossil-fuel based carbon emissions. Moreover, these countries are rapidly developing and energy demand has grown dramatically in the last two decades. A method is developed to estimate the spatial and seasonal flux of fossil-fuel consumption, thereby greatly improving the temporal and spatial resolution of anthropogenic carbon dioxide emissions. Currently, only national annual data for anthropogenic carbon emissions are available, and as such, no understanding of seasonal or sub-national patterns of emissions are possible. This methodology employs fuel distribution data from representative sectors of the fossil-fuel market to determine the temporal and spatial patterns of fuel consumption. These patterns of fuel consumption are then converted to patterns of carbon emissions. The annual total emissions estimates produced by this method are consistent to those maintained by the United Nations. Improved estimates of temporal and spatial resolution of the human based carbon emissions allows for better projections about future energy demands, carbon emissions, and ultimately the global carbon cycle.

Similar response patterns to topical minoxidil foam 5% in frontal and vertex scalp of men with androgenetic alopecia: a microarray analysis.

PubMed

Mirmirani, P; Consolo, M; Oyetakin-White, P; Baron, E; Leahy, P; Karnik, P

2015-06-01

There are regional variations in the scalp hair miniaturization seen in androgenetic alopecia (AGA). Use of topical minoxidil can lead to reversal of miniaturization in the vertex scalp. However, its effects on other scalp regions have been less well studied. To determine whether scalp biopsies from men with AGA show variable gene expression before and after 8 weeks of treatment with minoxidil topical foam 5% (MTF) vs. placebo. A placebo-controlled double-blinded prospective pilot study of MTF vs. placebo was conducted in 16 healthy men aged 18-49 years with Hamilton-Norwood type IV-V thinning. The subjects were asked to apply the treatment (active drug or placebo) to the scalp twice daily for 8 weeks. Stereotactic scalp photographs were taken at the baseline and final visits, to monitor global hair growth. Scalp biopsies were taken at the leading edge of hair loss from the frontal and vertex scalp before and after treatment with MTF and placebo, and microarray analysis was performed using the Affymetrix GeneChip HG U133 Plus 2.0. Global stereotactic photographs showed that MTF induced hair growth in both the frontal and vertex scalp of patients with AGA. Regional differences in gene expression profiles were observed before treatment. However, MTF treatment induced the expression of hair keratin-associated genes and decreased the expression of epidermal differentiation complex and inflammatory genes in both scalp regions. These data suggest that MTF is effective in the treatment of both the frontal and vertex scalp of patients with AGA. © 2014 British Association of Dermatologists.

Inflammatory Gene Regulatory Networks in Amnion Cells Following Cytokine Stimulation: Translational Systems Approach to Modeling Human Parturition

PubMed Central

Summerfield, Taryn L.; Yu, Lianbo; Gulati, Parul; Zhang, Jie; Huang, Kun; Romero, Roberto; Kniss, Douglas A.

2011-01-01

A majority of the studies examining the molecular regulation of human labor have been conducted using single gene approaches. While the technology to produce multi-dimensional datasets is readily available, the means for facile analysis of such data are limited. The objective of this study was to develop a systems approach to infer regulatory mechanisms governing global gene expression in cytokine-challenged cells in vitro, and to apply these methods to predict gene regulatory networks (GRNs) in intrauterine tissues during term parturition. To this end, microarray analysis was applied to human amnion mesenchymal cells (AMCs) stimulated with interleukin-1β, and differentially expressed transcripts were subjected to hierarchical clustering, temporal expression profiling, and motif enrichment analysis, from which a GRN was constructed. These methods were then applied to fetal membrane specimens collected in the absence or presence of spontaneous term labor. Analysis of cytokine-responsive genes in AMCs revealed a sterile immune response signature, with promoters enriched in response elements for several inflammation-associated transcription factors. In comparison to the fetal membrane dataset, there were 34 genes commonly upregulated, many of which were part of an acute inflammation gene expression signature. Binding motifs for nuclear factor-κB were prominent in the gene interaction and regulatory networks for both datasets; however, we found little evidence to support the utilization of pathogen-associated molecular pattern (PAMP) signaling. The tissue specimens were also enriched for transcripts governed by hypoxia-inducible factor. The approach presented here provides an uncomplicated means to infer global relationships among gene clusters involved in cellular responses to labor-associated signals. PMID:21655103

Quantitative Mass Spectrometry Reveals Changes in Histone H2B Variants as Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation*

PubMed Central

Rea, Matthew; Jiang, Tingting; Eleazer, Rebekah; Eckstein, Meredith; Marshall, Alan G.; Fondufe-Mittendorf, Yvonne N.

2016-01-01

Exposure to inorganic arsenic, a ubiquitous environmental toxic metalloid, leads to carcinogenesis. However, the mechanism is unknown. Several studies have shown that inorganic arsenic exposure alters specific gene expression patterns, possibly through alterations in chromatin structure. While most studies on understanding the mechanism of chromatin-mediated gene regulation have focused on histone post-translational modifications, the role of histone variants remains largely unknown. Incorporation of histone variants alters the functional properties of chromatin. To understand the global dynamics of chromatin structure and function in arsenic-mediated carcinogenesis, analysis of the histone variants incorporated into the nucleosome and their covalent modifications is required. Here we report the first global mass spectrometric analysis of histone H2B variants as cells undergo arsenic-mediated epithelial to mesenchymal transition. We used electron capture dissociation-based top-down tandem mass spectrometry analysis validated with quantitative reverse transcription real-time polymerase chain reaction to identify changes in the expression levels of H2B variants in inorganic arsenic-mediated epithelial-mesenchymal transition. We identified changes in the expression levels of specific histone H2B variants in two cell types, which are dependent on dose and length of exposure of inorganic arsenic. In particular, we found increases in H2B variants H2B1H/1K/1C/1J/1O and H2B2E/2F, and significant decreases in H2B1N/1D/1B as cells undergo inorganic arsenic-mediated epithelial-mesenchymal transition. The analysis of these histone variants provides a first step toward an understanding of the functional significance of the diversity of histone structures, especially in inorganic arsenic-mediated gene expression and carcinogenesis. PMID:27169413

Impact of Pyrrolidine Dithiocarbamate and Interleukin-6 on Mammalian Target of Rapamycin Complex 1 Regulation and Global Protein TranslationS⃞

PubMed Central

Song, Shaoming; Abdelmohsen, Kotb; Zhang, Yongqing; Becker, Kevin G.; Gorospe, Myriam

2011-01-01

Interleukin-6 (IL-6) is a proinflammatory cytokine that exerts a wide range of cellular, physiological, and pathophysiological responses. Pyrrolidine dithiocarbamate (PDTC) antagonizes the cellular responsiveness to IL-6 through impairment in signal transducer and activator of transcription-3 activation and downstream signaling. To further elucidate the biological properties of PDTC, global gene expression profiling of human HepG2 hepatocellular carcinoma cells was carried out after treatment with PDTC or IL-6 for up to 8 h. Through an unbiased pathway analysis method, gene array analysis showed dramatic and temporal differences in expression changes in response to PDTC versus IL-6. A significant number of genes associated with metabolic pathways, inflammation, translation, and mitochondrial function were changed, with ribosomal protein genes and DNA damage-inducible transcript 4 protein (DDIT4) primarily up-regulated with PDTC but down-regulated with IL-6. Quantitative polymerase chain reaction and Western blot analyses validated the microarray data and showed the reciprocal expression pattern of the mammalian target of rapamycin (mTOR)-negative regulator DDIT4 in response to PDTC versus IL-6. Cell treatment with PDTC resulted in a rapid and sustained activation of Akt and subsequently blocked the IL-6-mediated increase in mTOR complex 1 function through up-regulation in DDIT4 expression. Conversely, down-regulation of DDIT4 with small interfering RNA dampened the capacity of PDTC to block IL-6-dependent mTOR activation. The overall protein biosynthetic capacity of the cells was severely blunted by IL-6 but increased in a rapamycin-independent pathway by PDTC. These results demonstrate a critical effect of PDTC on mTOR complex 1 function and provide evidence that PDTC can reverse IL-6-related signaling via induction of DDIT4. PMID:21917559

Global transcriptome analysis of eukaryotic genes affected by gromwell extract.

PubMed

Bang, Soohyun; Lee, Dohyun; Kim, Hanhe; Park, Jiyong; Bahn, Yong-Sun

2014-02-01

Gromwell is known to have diverse pharmacological, cosmetic and nutritional benefits for humans. Nevertheless, the biological influence of gromwell extract (GE) on the general physiology of eukaryotic cells remains unknown. In this study a global transcriptome analysis was performed to identify genes affected by the addition of GE with Cryptococcus neoformans as the model system. In response to GE treatment, genes involved in signal transduction were immediately regulated, and the evolutionarily conserved sets of genes involved in the core cellular functions, including DNA replication, RNA transcription/processing and protein translation/processing, were generally up-regulated. In contrast, a number of genes involved in carbohydrate metabolism and transport, inorganic ion transport and metabolism, post-translational modification/protein turnover/chaperone functions and signal transduction were down-regulated. Among the GE-responsive genes that are also evolutionarily conserved in the human genome, the expression patterns of YSA1, TPO2, CFO1 and PZF1 were confirmed by northern blot analysis. Based on the functional characterization of some GE-responsive genes, it was found that GE treatment may promote cellular tolerance against a variety of environmental stresses in eukaryotes. GE treatment affects the expression levels of a significant portion of the Cryptococcus genome, implying that GE significantly affects the general physiology of eukaryotic cells. © 2013 Society of Chemical Industry.

Pituitary genomic expression profiles of steers are altered by grazing of high vs. low endophyte-infected tall fescue forages.

PubMed

Li, Qing; Hegge, Raquel; Bridges, Phillip J; Matthews, James C

2017-01-01

Consumption of ergot alkaloid-containing tall fescue grass impairs several metabolic, vascular, growth, and reproductive processes in cattle, collectively producing a clinical condition known as "fescue toxicosis." Despite the apparent association between pituitary function and these physiological parameters, including depressed serum prolactin; no reports describe the effect of fescue toxicosis on pituitary genomic expression profiles. To identify candidate regulatory mechanisms, we compared the global and selected targeted mRNA expression patterns of pituitaries collected from beef steers that had been randomly assigned to undergo summer-long grazing (89 to 105 d) of a high-toxic endophyte-infected tall fescue pasture (HE; 0.746 μg/g ergot alkaloids; 5.7 ha; n = 10; BW = 267 ± 14.5 kg) or a low-toxic endophyte tall fescue-mixed pasture (LE; 0.023 μg/g ergot alkaloids; 5.7 ha; n = 9; BW = 266 ± 10.9 kg). As previously reported, in the HE steers, serum prolactin and body weights decreased and a potential for hepatic gluconeogenesis from amino acid-derived carbons increased. In this manuscript, we report that the pituitaries of HE steers had 542 differentially expressed genes (P < 0.001, false discovery rate ≤ 4.8%), and the pattern of altered gene expression was dependent (P < 0.001) on treatment. Integrated Pathway Analysis revealed that canonical pathways central to prolactin production, secretion, or signaling were affected, in addition to those related to corticotropin-releasing hormone signaling, melanocyte development, and pigmentation signaling. Targeted RT-PCR analysis corroborated these findings, including decreased (P < 0.05) expression of DRD2, PRL, POU1F1, GAL, and VIP and that of POMC and PCSK1, respectively. Canonical pathway analysis identified HE-dependent alteration in signaling of additional pituitary-derived hormones, including growth hormone and GnRH. We conclude that consumption of endophyte-infected tall fescue alters the pituitary transcriptome profiles of steers in a manner consistent with their negatively affected physiological parameters.

Gene Expression Networks Underlying Ovarian Development in Wild Largemouth Bass (Micropterus salmoides)

PubMed Central

Martyniuk, Christopher J.; Prucha, Melinda S.; Doperalski, Nicholas J.; Antczak, Philipp; Kroll, Kevin J.; Falciani, Francesco; Barber, David S.; Denslow, Nancy D.

2013-01-01

Background Oocyte maturation in fish involves numerous cell signaling cascades that are activated or inhibited during specific stages of oocyte development. The objectives of this study were to characterize molecular pathways and temporal gene expression patterns throughout a complete breeding cycle in wild female largemouth bass to improve understanding of the molecular sequence of events underlying oocyte maturation. Methods Transcriptomic analysis was performed on eight morphologically diverse stages of the ovary, including primary and secondary stages of oocyte growth, ovulation, and atresia. Ovary histology, plasma vitellogenin, 17β-estradiol, and testosterone were also measured to correlate with gene networks. Results Global expression patterns revealed dramatic differences across ovarian development, with 552 and 2070 genes being differentially expressed during both ovulation and atresia respectively. Gene set enrichment analysis (GSEA) revealed that early primary stages of oocyte growth involved increases in expression of genes involved in pathways of B-cell and T-cell receptor-mediated signaling cascades and fibronectin regulation. These pathways as well as pathways that included adrenergic receptor signaling, sphingolipid metabolism and natural killer cell activation were down-regulated at ovulation. At atresia, down-regulated pathways included gap junction and actin cytoskeleton regulation, gonadotrope and mast cell activation, and vasopressin receptor signaling and up-regulated pathways included oxidative phosphorylation and reactive oxygen species metabolism. Expression targets for luteinizing hormone signaling were low during vitellogenesis but increased 150% at ovulation. Other networks found to play a significant role in oocyte maturation included those with genes regulated by members of the TGF-beta superfamily (activins, inhibins, bone morphogenic protein 7 and growth differentiation factor 9), neuregulin 1, retinoid X receptor, and nerve growth factor family. Conclusions This study offers novel insight into the gene networks underlying vitellogenesis, ovulation and atresia and generates new hypotheses about the cellular pathways regulating oocyte maturation. PMID:23527095

Genome-wide transcriptome analysis of the transition from primary to secondary stem development in Populus trichocarpa

PubMed Central

2010-01-01

Background With its genome sequence and other experimental attributes, Populus trichocarpa has become the model species for genomic studies of wood development. Wood is derived from secondary growth of tree stems, and begins with the development of a ring of vascular cambium in the young developing stem. The terminal region of the developing shoot provides a steep developmental gradient from primary to secondary growth that facilitates identification of genes that play specialized functions during each of these phases of growth. Results Using a genomic microarray representing the majority of the transcriptome, we profiled gene expression in stem segments that spanned primary to secondary growth. We found 3,016 genes that were differentially expressed during stem development (Q-value ≤ 0.05; >2-fold expression variation), and 15% of these genes encode proteins with no significant identities to known genes. We identified all gene family members putatively involved in secondary growth for carbohydrate active enzymes, tubulins, actins, actin depolymerizing factors, fasciclin-like AGPs, and vascular development-associated transcription factors. Almost 70% of expressed transcription factors were upregulated during the transition to secondary growth. The primary shoot elongation region of the stem contained specific carbohydrate active enzyme and expansin family members that are likely to function in primary cell wall synthesis and modification. Genes involved in plant defense and protective functions were also dominant in the primary growth region. Conclusion Our results describe the global patterns of gene expression that occur during the transition from primary to secondary stem growth. We were able to identify three major patterns of gene expression and over-represented gene ontology categories during stem development. The new regulatory factors and cell wall biogenesis genes that we identified provide candidate genes for further functional characterization, as well as new tools for molecular breeding and biotechnology aimed at improvement of tree growth rate, crown form, and wood quality. PMID:20199690

Instruction of haematopoietic lineage choices, evolution of transcriptional landscapes and cancer stem cell hierarchies derived from an AML1-ETO mouse model

PubMed Central

Cabezas-Wallscheid, Nina; Eichwald, Victoria; de Graaf, Jos; Löwer, Martin; Lehr, Hans-Anton; Kreft, Andreas; Eshkind, Leonid; Hildebrandt, Andreas; Abassi, Yasmin; Heck, Rosario; Dehof, Anna Katharina; Ohngemach, Svetlana; Sprengel, Rolf; Wörtge, Simone; Schmitt, Steffen; Lotz, Johannes; Meyer, Claudius; Kindler, Thomas; Zhang, Dong-Er; Kaina, Bernd; Castle, John C; Trumpp, Andreas; Sahin, Ugur; Bockamp, Ernesto

2013-01-01

The t(8;21) chromosomal translocation activates aberrant expression of the AML1-ETO (AE) fusion protein and is commonly associated with core binding factor acute myeloid leukaemia (CBF AML). Combining a conditional mouse model that closely resembles the slow evolution and the mosaic AE expression pattern of human t(8;21) CBF AML with global transcriptome sequencing, we find that disease progression was characterized by two principal pathogenic mechanisms. Initially, AE expression modified the lineage potential of haematopoietic stem cells (HSCs), resulting in the selective expansion of the myeloid compartment at the expense of normal erythro- and lymphopoiesis. This lineage skewing was followed by a second substantial rewiring of transcriptional networks occurring in the trajectory to manifest leukaemia. We also find that both HSC and lineage-restricted granulocyte macrophage progenitors (GMPs) acquired leukaemic stem cell (LSC) potential being capable of initiating and maintaining the disease. Finally, our data demonstrate that long-term expression of AE induces an indolent myeloproliferative disease (MPD)-like myeloid leukaemia phenotype with complete penetrance and that acute inactivation of AE function is a potential novel therapeutic option. PMID:24124051

AN OVERVIEW OF THE STRESSORS AND ECOLOGICAL IMPACTS ASSOCIATED WITH REGIONAL AND GLOBAL PATTERNS OF POPULATION, LAND USE, AND LAND COVER CHANGE

EPA Science Inventory

This report provides an overview of land use and land cover (LULC) change and re~ona1 to global patterns of that change and responses. Human activities now dominate the Earth's global ecosystem and LULC change is one of the most pervasive and influential of those activities. LULC...

Visual Attention to Global and Local Stimulus Properties in 6-Month-Old Infants: Individual Differences and Event-Related Potentials

ERIC Educational Resources Information Center

Guy, Maggie W.; Reynolds, Greg D.; Zhang, Dantong

2013-01-01

Event-related potentials (ERPs) were utilized in an investigation of 21 six-month-olds' attention to and processing of global and local properties of hierarchical patterns. Overall, infants demonstrated an advantage for processing the overall configuration (i.e., global properties) of local features of hierarchical patterns; however,…

Transcriptome-Wide Changes in Chlamydomonas reinhardtii Gene Expression Regulated by Carbon Dioxide and the CO2-Concentrating Mechanism Regulator CIA5/CCM1[W][OA

PubMed Central

Fang, Wei; Si, Yaqing; Douglass, Stephen; Casero, David; Merchant, Sabeeha S.; Pellegrini, Matteo; Ladunga, Istvan; Liu, Peng; Spalding, Martin H.

2012-01-01

We used RNA sequencing to query the Chlamydomonas reinhardtii transcriptome for regulation by CO2 and by the transcription regulator CIA5 (CCM1). Both CO2 and CIA5 are known to play roles in acclimation to low CO2 and in induction of an essential CO2-concentrating mechanism (CCM), but less is known about their interaction and impact on the whole transcriptome. Our comparison of the transcriptome of a wild type versus a cia5 mutant strain under three different CO2 conditions, high CO2 (5%), low CO2 (0.03 to 0.05%), and very low CO2 (<0.02%), provided an entry into global changes in the gene expression patterns occurring in response to the interaction between CO2 and CIA5. We observed a massive impact of CIA5 and CO2 on the transcriptome, affecting almost 25% of all Chlamydomonas genes, and we discovered an array of gene clusters with distinctive expression patterns that provide insight into the regulatory interaction between CIA5 and CO2. Several individual clusters respond primarily to either CIA5 or CO2, providing access to genes regulated by one factor but decoupled from the other. Three distinct clusters clearly associated with CCM-related genes may represent a rich source of candidates for new CCM components, including a small cluster of genes encoding putative inorganic carbon transporters. PMID:22634760

Differential accumulation of volatile terpene and terpene synthase mRNAs during lavender (Lavandula angustifolia and L. x intermedia) inflorescence development.

PubMed

Guitton, Yann; Nicolè, Florence; Moja, Sandrine; Valot, Nadine; Legrand, Sylvain; Jullien, Frédéric; Legendre, Laurent

2010-02-01

Despite the commercial importance of Lavandula angustifolia Mill. and L. x intermedia Emeric ex Loisel floral essential oils (EOs), no information is currently available on potential changes in individual volatile organic compound (VOC) content during inflorescence development. Calyces were found to be the main sites of VOC accumulation. The 20 most abundant VOCs could be separated into three sub-groups according to their patterns of change in concentration The three groups of VOCs sequentially dominated the global scent bouquet of inflorescences, the transition between the first and second groups occurring around the opening of the first flower of the inflorescence and the one between the second and third groups at the start of seed set. Changes in calyx VOC accumulation were linked to the developmental stage of individual flowers. Leaves accumulated a smaller number of VOCs which were a subset of those seen in preflowering inflorescences. Their nature and content remained constant during the growing season. Quantitative real time polymerase chain reaction assessments of the expression of two terpene synthase (TPS) genes, LaLIMS and LaLINS, revealed similar trends between their patterns of expression and those of their VOC products. Molecular and chemical analyses suggest that changes in TPS expression occur during lavender inflorescence development and lead to changes in EO composition. Both molecular data and terpene analysis support the findings that changes in biosynthesis of terpene occurred during inflorescence development.

Microenvironmental change as a mechanism to study global change.

NASA Astrophysics Data System (ADS)

Lortie, C. J.

2016-12-01

Global change is a set of significant processes that influence all aspects of ecosystem functioning and often-natural services within Santa Barbara County. The sensitivity of coastal and urban systems is certainly very high. However, profound changes are also predicted for arid and semi-arid systems globally, and California is no exception. These dryland systems are less buffered by oceanic processes and typically express high inter-annual variation in precipitation and temperatures in addition to perturbations associated with long-term droughts. However, climate estimates and downscaled values can present challenges in providing evidence at the scale relevant to individual species or individuals, and the importance of biotic interactions must be coupled to these estimates in space and time. Coupled indicators of key micro-environmental measures to both positive and negative interactions between foundation species and other organisms provide a metric of buffering capacity and resilience to global change at fine spatial scales. Consequently, the primary objective of this research project is to provide both the a well-articulated, ecologically relevant micro-environmental big data measure of global change within Santa Barbara County and a coupled estimate of concurrent changes in interactions in key species within the region. Shrubs directly and indirectly buffered local changes in the microenvironment thereby functioning as refuges for other species within arid and semi-arid regions subject to dramatic global change drivers. The following major patterns were identified: (i) shrub micro-environments reduce the level of stress and amplitude of variation associated with temperature and moisture, (ii) many plant and animal species including threatened lizards are relatively more common with shrubs within the region, and (iii) the variation in the interaction patterns between species relates to the extent of amelioration provided by shrub-biodiversity complexes within the region. The ecological theory of positive plant interactions scaling to other species as a restoration and management tool is a dominant and rapidly evolving field of research. Micro-environmental sensor arrays are a scientifically valid approach to identify meaningful localized change with biotic interactions.

Global-Local Precedence in the Perception of Facial Age and Emotional Expression by Children with Autism and Other Developmental Disabilities

ERIC Educational Resources Information Center

Gross, Thomas F.

2005-01-01

Global information processing and perception of facial age and emotional expression was studied in children with autism, language disorders, mental retardation, and a clinical control group. Children were given a global-local task and asked to recognize age and emotion in human and canine faces. Children with autism made fewer global responses and…

Divergent and nonuniform gene expression patterns in mouse brain

PubMed Central

Morris, John A.; Royall, Joshua J.; Bertagnolli, Darren; Boe, Andrew F.; Burnell, Josh J.; Byrnes, Emi J.; Copeland, Cathy; Desta, Tsega; Fischer, Shanna R.; Goldy, Jeff; Glattfelder, Katie J.; Kidney, Jolene M.; Lemon, Tracy; Orta, Geralyn J.; Parry, Sheana E.; Pathak, Sayan D.; Pearson, Owen C.; Reding, Melissa; Shapouri, Sheila; Smith, Kimberly A.; Soden, Chad; Solan, Beth M.; Weller, John; Takahashi, Joseph S.; Overly, Caroline C.; Lein, Ed S.; Hawrylycz, Michael J.; Hohmann, John G.; Jones, Allan R.

2010-01-01

Considerable progress has been made in understanding variations in gene sequence and expression level associated with phenotype, yet how genetic diversity translates into complex phenotypic differences remains poorly understood. Here, we examine the relationship between genetic background and spatial patterns of gene expression across seven strains of mice, providing the most extensive cellular-resolution comparative analysis of gene expression in the mammalian brain to date. Using comprehensive brainwide anatomic coverage (more than 200 brain regions), we applied in situ hybridization to analyze the spatial expression patterns of 49 genes encoding well-known pharmaceutical drug targets. Remarkably, over 50% of the genes examined showed interstrain expression variation. In addition, the variability was nonuniformly distributed across strain and neuroanatomic region, suggesting certain organizing principles. First, the degree of expression variance among strains mirrors genealogic relationships. Second, expression pattern differences were concentrated in higher-order brain regions such as the cortex and hippocampus. Divergence in gene expression patterns across the brain could contribute significantly to variations in behavior and responses to neuroactive drugs in laboratory mouse strains and may help to explain individual differences in human responsiveness to neuroactive drugs. PMID:20956311

Binary Gene Expression Patterning of the Molt Cycle: The Case of Chitin Metabolism

PubMed Central

Abehsera, Shai; Glazer, Lilah; Tynyakov, Jenny; Plaschkes, Inbar; Chalifa-Caspi, Vered; Khalaila, Isam; Aflalo, Eliahu D.; Sagi, Amir

2015-01-01

In crustaceans, like all arthropods, growth is accompanied by a molting cycle. This cycle comprises major physiological events in which mineralized chitinous structures are built and degraded. These events are in turn governed by genes whose patterns of expression are presumably linked to the molting cycle. To study these genes we performed next generation sequencing and constructed a molt-related transcriptomic library from two exoskeletal-forming tissues of the crayfish Cherax quadricarinatus, namely the gastrolith and the mandible cuticle-forming epithelium. To simplify the study of such a complex process as molting, a novel approach, binary patterning of gene expression, was employed. This approach revealed that key genes involved in the synthesis and breakdown of chitin exhibit a molt-related pattern in the gastrolith-forming epithelium. On the other hand, the same genes in the mandible cuticle-forming epithelium showed a molt-independent pattern of expression. Genes related to the metabolism of glucosamine-6-phosphate, a chitin precursor synthesized from simple sugars, showed a molt-related pattern of expression in both tissues. The binary patterning approach unfolds typical patterns of gene expression during the molt cycle of a crustacean. The use of such a simplifying integrative tool for assessing gene patterning seems appropriate for the study of complex biological processes. PMID:25919476

Changes in global gene expression during in vitro decidualization of rat endometrial stromal cells

PubMed Central

Vallejo, Griselda; Maschi, Darío; Citrinovitz, Ana Cecilia Mestre; Aiba, Kazuhiro; Maronna, Ricardo; Yohai, Victor; Ko, Minoru S. H.; Beato, Miguel; Saragüeta, Patricia

2009-01-01

During the preimplantation phase of pregnancy the endometrial stroma differentiates into decidua, a process that implies numerous morphological changes and is an example of physiological transdifferentiation. Here we show that UIII rat endometrial stromal cells cultured in the presence of calf serum acquired morphological features of decidual cells and expressed decidual markers. To identify genes involved in decidualization we compared gene expression patterns of control and decidualized UIII cells using cDNA microarray. We found 322 annotated genes exhibiting significant differences in expression (>3 fold, FDR > 0.005), of which 312 have not been previously related to decidualization. Analysis of overrepresented functions revealed that protein synthesis, gene expression and chromatin architecture and remodeling are the most relevant modified functions during decidualization. Relevant genes are also found in the functional terms differentiation, cell proliferation, signal transduction, and matrix/structural proteins. Several of these new genes involved in decidualization (Csdc2, Trim27, Eef1a1, Bmp1, Wt1, Aes, Gna12, and Men1) are shown to be also regulated in uterine decidua during normal pregnancy. Thus, the UIII cell culture model will allow future mechanistic studies to define the transcriptional network regulating reprogramming of stromal cells into decidual cells. PMID:19780023

La Niña diversity and Northwest Indian Ocean Rim teleconnections

USGS Publications Warehouse

Hoell, Andrew; Funk, Christopher C.; Barlow, Mathew

2014-01-01

The differences in tropical Pacific sea surface temperature (SST) expressions of El Niño-Southern Oscillation (ENSO) events of the same phase have been linked with different global atmospheric circulation patterns. This study examines the dynamical forcing of precipitation during October–December (OND) and March–May (MAM) over East Africa and during December–March (DJFM) over Central-Southwest Asia for 1950–2010 associated with four tropical Pacific SST patterns characteristic of La Niña events, the cold phase of ENSO. The self-organizing map method along with a statistical distinguishability test was used to isolate La Niña events, and seasonal precipitation forcing was investigated in terms of the tropical overturning circulation and thermodynamic and moisture budgets. Recent La Niña events with strong opposing SST anomalies between the central and western Pacific Ocean (phases 3 and 4), force the strongest global circulation modifications and drought over the Northwest Indian Ocean Rim. Over East Africa during MAM and OND, subsidence is forced by an enhanced tropical overturning circulation and precipitation reductions are exacerbated by increases in moisture flux divergence. Over Central-Southwest Asia during DJFM, the thermodynamic forcing of subsidence is primarily responsible for precipitation reductions, with moisture flux divergence acting as a secondary mechanism to reduce precipitation. Eastern Pacific La Niña events in the absence of west Pacific SST anomalies (phases 1 and 2), are associated with weaker global teleconnections, particularly over the Indian Ocean Rim. The weak regional teleconnections result in statistically insignificant precipitation modifications over East Africa and Central-Southwest Asia.

Chromium-picolinate therapy in diabetes care: molecular and subcellular profiling revealed a necessity for individual outcome prediction, personalised treatment algorithms & new guidelines

PubMed Central

Yeghiazaryan, Kristina; Peeva, Viktoriya; Shenoy, Aparna; Schild, Hans H.; Golubnitschaja, Olga

2013-01-01

Aims Global figures clearly demonstrate inadequacy of current diabetes care: every 10 seconds one patient dies of diabetes-related pathologies. Nephropathy is the leading secondary complication of the disease. Nutritional supplement by chromium-picolinate is assumed to have beneficial therapeutic effects. However, potential toxic effects reported increase concerns about safety of chromium-picolinate. The experimental design aimed at determining, whether the treatment with clinically relevant doses of chromium-picolinate can harm through DNA damage and extensive alterations in central detoxification / cell-cycle regulating pathways in treatment of diabetes. Methods Well-acknowledged animal model of db/db-mice and clinically relevant doses of chromium-picolinate were used. As an index of DNA-damage, measurement of DNA-breaks was performed using “Comet Assay”-analysis. Individual and group-specific expression patterns of SOD-1 and P53 were evaluated to give a clue about central detoxification and cell-cycle regulating pathways under treatment conditions. The study was performed in a double-blind manner. Results Experimental data revealed highly individual reaction under treatment conditions. However, group-specific patterns were monitored: highest amount of damaged DNA - under the longest treatment with high doses, in contrast to groups with low doses of chromium-picolinate. Comet patterns were intermediate between untreated diabetized and control animals. Expression patterns demonstrated a correlation with subcellular imaging and dosage-dependent suppression under chromium-picolinate treatment. Conclusions This article highlights possible risks for individual long-term effects, when chromium-picolinate is used freely as a therapeutic nutritional modality agent without application of advanced diagnostic tools to predict risks and individual outcomes. Targeted measures require a creation of new guidelines for advanced Diabetes care. PMID:21470100

Chromium-picolinate therapy in diabetes care: molecular and subcellular profiling revealed a necessity for individual outcome prediction, personalised treatment algorithms and new guidelines.

PubMed

Yeghiazaryan, Kristina; Peeva, Viktoriya; Shenoy, Aparna; Schild, Hans H; Golubnitschaja, Olga

2011-04-01

Global figures clearly demonstrate inadequacy of current diabetes care: every 10 seconds one patient dies of diabetes-related pathologies. Nephropathy is the leading secondary complication of the disease. Nutritional supplement by chromium-picolinate is assumed to have beneficial therapeutic effects. However, potential toxic effects reported increase concerns about safety of chromium-picolinate. The experimental design aimed at determining, whether the treatment with clinically relevant doses of chromium-picolinate can harm through DNA damage and extensive alterations in central detoxification / cell-cycle regulating pathways in treatment of diabetes. Well-acknowledged animal model of db/db-mice and clinically relevant doses of chromium-picolinate were used. As an index of DNA-damage, measurement of DNA-breaks was performed using "Comet Assay"-analysis. Individual and group-specific expression patterns of SOD-1 and P53 were evaluated to give a clue about central detoxification and cell-cycle regulating pathways under treatment conditions. The study was performed in a double-blind manner. Experimental data revealed highly individual reaction under treatment conditions. However, group-specific patterns were monitored: highest amount of damaged DNA--under the longest treatment with high doses, in contrast to groups with low doses of chromium-picolinate. Comet patterns were intermediate between untreated diabetised and control animals. Expression patterns demonstrated a correlation with subcellular imaging and dosage-dependent suppression under chromium-picolinate treatment. This article highlights possible risks for individual long-term effects, when chromium-picolinate is used freely as a therapeutic nutritional modality agent without application of advanced diagnostic tools to predict risks and individual outcomes. Targeted measures require a creation of new guidelines for advanced Diabetes care.

RNA-seq analysis of the gonadal transcriptome during Alligator mississippiensis temperature-dependent sex determination and differentiation.

PubMed

Yatsu, Ryohei; Miyagawa, Shinichi; Kohno, Satomi; Parrott, Benjamin B; Yamaguchi, Katsushi; Ogino, Yukiko; Miyakawa, Hitoshi; Lowers, Russell H; Shigenobu, Shuji; Guillette, Louis J; Iguchi, Taisen

2016-01-25

The American alligator (Alligator mississippiensis) displays temperature-dependent sex determination (TSD), in which incubation temperature during embryonic development determines the sexual fate of the individual. However, the molecular mechanisms governing this process remain a mystery, including the influence of initial environmental temperature on the comprehensive gonadal gene expression patterns occurring during TSD. Our characterization of transcriptomes during alligator TSD allowed us to identify novel candidate genes involved in TSD initiation. High-throughput RNA sequencing (RNA-seq) was performed on gonads collected from A. mississippiensis embryos incubated at both a male and a female producing temperature (33.5 °C and 30 °C, respectively) in a time series during sexual development. RNA-seq yielded 375.2 million paired-end reads, which were mapped and assembled, and used to characterize differential gene expression. Changes in the transcriptome occurring as a function of both development and sexual differentiation were extensively profiled. Forty-one differentially expressed genes were detected in response to incubation at male producing temperature, and included genes such as Wnt signaling factor WNT11, histone demethylase KDM6B, and transcription factor C/EBPA. Furthermore, comparative analysis of development- and sex-dependent differential gene expression revealed 230 candidate genes involved in alligator sex determination and differentiation, and early details of the suspected male-fate commitment were profiled. We also discovered sexually dimorphic expression of uncharacterized ncRNAs and other novel elements, such as unique expression patterns of HEMGN and ARX. Twenty-five of the differentially expressed genes identified in our analysis were putative transcriptional regulators, among which were MYBL2, MYCL, and HOXC10, in addition to conventional sex differentiation genes such as SOX9, and FOXL2. Inferred gene regulatory network was constructed, and the gene-gene and temperature-gene interactions were predicted. Gonadal global gene expression kinetics during sex determination has been extensively profiled for the first time in a TSD species. These findings provide insights into the genetic framework underlying TSD, and expand our current understanding of the developmental fate pathways during vertebrate sex determination.

Transcriptomic analysis of Salmonella desiccation resistance.

PubMed

Li, Haiping; Bhaskara, Anuhya; Megalis, Christina; Tortorello, Mary Lou

2012-12-01

The survival of Salmonella in low moisture foods and processing environments remains a great challenge for the food industry and public health. To explore the mechanisms of Salmonella desiccation resistance, we studied the transcriptomic responses in Salmonella Tennessee (Tennessee), using Salmonella Typhimurium LT2 (LT2), a strain weakly resistant to desiccation, as a reference strain. In response to 2 h of air-drying at 11% equilibrated relative humidity, approximately one-fourth of the open reading frames (ORFs) in the Tennessee genome and one-fifth in LT2 were differentially expressed (>2-fold). Among all differentially expressed functional groups (>5-fold) in both strains, the expression fold change associated with fatty acid metabolism was the highest, and constituted 51% and 35% of the total expression fold change in Tennessee and LT2, respectively. Tennessee showed greater changes in expression of genes associated with stress response and envelope modification than LT2, while showing lesser changes in protein biosynthesis expression. Expression of flagella genes was significantly more inhibited in stationary phase cells of Tennessee than LT2 both before and after desiccation. The accumulation of the osmolyte trehalose was significantly induced by desiccation in Tennessee, but no increase was detectable in LT2, which is consistent with the expression patterns of the entire trehalose biosynthesis and degradation pathways in both strains. Results from this study present a global view of the dynamic desiccation responses in Salmonella, which will guide future research efforts to control Salmonella in low moisture environments.

Pattern identification in time-course gene expression data with the CoGAPS matrix factorization.

PubMed

Fertig, Elana J; Stein-O'Brien, Genevieve; Jaffe, Andrew; Colantuoni, Carlo

2014-01-01

Patterns in time-course gene expression data can represent the biological processes that are active over the measured time period. However, the orthogonality constraint in standard pattern-finding algorithms, including notably principal components analysis (PCA), confounds expression changes resulting from simultaneous, non-orthogonal biological processes. Previously, we have shown that Markov chain Monte Carlo nonnegative matrix factorization algorithms are particularly adept at distinguishing such concurrent patterns. One such matrix factorization is implemented in the software package CoGAPS. We describe the application of this software and several technical considerations for identification of age-related patterns in a public, prefrontal cortex gene expression dataset.

RNA sequencing: current and prospective uses in metabolic research.

PubMed

Vikman, Petter; Fadista, Joao; Oskolkov, Nikolay

2014-10-01

Previous global RNA analysis was restricted to known transcripts in species with a defined transcriptome. Next generation sequencing has transformed transcriptomics by making it possible to analyse expressed genes with an exon level resolution from any tissue in any species without any a priori knowledge of which genes that are being expressed, splice patterns or their nucleotide sequence. In addition, RNA sequencing is a more sensitive technique compared with microarrays with a larger dynamic range, and it also allows for investigation of imprinting and allele-specific expression. This can be done for a cost that is able to compete with that of a microarray, making RNA sequencing a technique available to most researchers. Therefore RNA sequencing has recently become the state of the art with regards to large-scale RNA investigations and has to a large extent replaced microarrays. The only drawback is the large data amounts produced, which together with the complexity of the data can make a researcher spend far more time on analysis than performing the actual experiment. © 2014 Society for Endocrinology.

Differential gene expression between skin and cervix induced by the E7 oncoprotein in a transgenic mouse model

PubMed Central

Ibarra Sierra, E; Díaz Chávez, J; Cortés-Malagón, EM; Uribe-Figueroa, L; Hidalgo-Miranda, A; Lambert, PF; Gariglio, P

2013-01-01

HPV16 E7 oncoprotein expression in K14E7 transgenic mice induces cervical cancer after 6 months of treatment with the co-carcinogen 17β-estradiol. In untreated mice, E7 also induces skin tumors late in life albeit at low penetrance. These findings indicate that E7 alters cellular functions in cervix and skin so as to predispose these organs to tumorigenesis. Using microarrays, we determined the global genes expression profile in cervical and skin tissue of young adult K14E7 transgenic mice without estrogen treatment. In these tissues, the E7 oncoprotein altered the transcriptional pattern of genes involved in several biological processes including signal transduction, transport, metabolic process, cell adhesion, apoptosis, cell differentiation, immune response and inflammatory response. Among the E7-dysregulated genes were ones not previously known to be involved in cervical neoplasia including DMBT1, GLI1 and 17βHSD2 in cervix, as well as MMP2, 12, 14, 19 and 27 in skin. PMID:22980503

Differential gene expression between skin and cervix induced by the E7 oncoprotein in a transgenic mouse model.

PubMed

Ibarra Sierra, E; Díaz Chávez, J; Cortés-Malagón, E M; Uribe-Figueroa, L; Hidalgo-Miranda, A; Lambert, P F; Gariglio, P

2012-11-25

HPV16 E7 oncoprotein expression in K14E7 transgenic mice induces cervical cancer after 6 months of treatment with the co-carcinogen 17β-estradiol. In untreated mice, E7 also induces skin tumors late in life albeit at low penetrance. These findings indicate that E7 alters cellular functions in cervix and skin so as to predispose these organs to tumorigenesis. Using microarrays, we determined the global genes expression profile in cervical and skin tissue of young adult K14E7 transgenic mice without estrogen treatment. In these tissues, the E7 oncoprotein altered the transcriptional pattern of genes involved in several biological processes including signal transduction, transport, metabolic process, cell adhesion, apoptosis, cell differentiation, immune response and inflammatory response. Among the E7-dysregulated genes were ones not previously known to be involved in cervical neoplasia including DMBT1, GLI1 and 17βHSD2 in cervix, as well as MMP2, 12, 14, 19 and 27 in skin. Copyright © 2012 Elsevier Inc. All rights reserved.

An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development

PubMed Central

Benitez, Cecil M.; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T.; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H. Efsun; Zhang, Jiajing; Dekker, Joseph D.; Tucker, Haley O.; Chang, Howard Y.; Kim, Seung K.

2014-01-01

The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus. PMID:25330008

A powerful and flexible statistical framework for testing hypotheses of allele-specific gene expression from RNA-seq data

PubMed Central

Skelly, Daniel A.; Johansson, Marnie; Madeoy, Jennifer; Wakefield, Jon; Akey, Joshua M.

2011-01-01

Variation in gene expression is thought to make a significant contribution to phenotypic diversity among individuals within populations. Although high-throughput cDNA sequencing offers a unique opportunity to delineate the genome-wide architecture of regulatory variation, new statistical methods need to be developed to capitalize on the wealth of information contained in RNA-seq data sets. To this end, we developed a powerful and flexible hierarchical Bayesian model that combines information across loci to allow both global and locus-specific inferences about allele-specific expression (ASE). We applied our methodology to a large RNA-seq data set obtained in a diploid hybrid of two diverse Saccharomyces cerevisiae strains, as well as to RNA-seq data from an individual human genome. Our statistical framework accurately quantifies levels of ASE with specified false-discovery rates, achieving high reproducibility between independent sequencing platforms. We pinpoint loci that show unusual and biologically interesting patterns of ASE, including allele-specific alternative splicing and transcription termination sites. Our methodology provides a rigorous, quantitative, and high-resolution tool for profiling ASE across whole genomes. PMID:21873452

An Orchestrated Intron Retention Program in Meiosis Controls Timely Usage of Transcripts during Germ Cell Differentiation.

PubMed

Naro, Chiara; Jolly, Ariane; Di Persio, Sara; Bielli, Pamela; Setterblad, Niclas; Alberdi, Antonio J; Vicini, Elena; Geremia, Raffaele; De la Grange, Pierre; Sette, Claudio

2017-04-10

Global transcriptome reprogramming during spermatogenesis ensures timely expression of factors in each phase of male germ cell differentiation. Spermatocytes and spermatids require particularly extensive reprogramming of gene expression to switch from mitosis to meiosis and to support gamete morphogenesis. Here, we uncovered an extensive alternative splicing program during this transmeiotic differentiation. Notably, intron retention was largely the most enriched pattern, with spermatocytes showing generally higher levels of retention compared with spermatids. Retained introns are characterized by weak splice sites and are enriched in genes with strong relevance for gamete function. Meiotic intron-retaining transcripts (IRTs) were exclusively localized in the nucleus. However, differently from other developmentally regulated IRTs, they are stable RNAs, showing longer half-life than properly spliced transcripts. Strikingly, fate-mapping experiments revealed that IRTs are recruited onto polyribosomes days after synthesis. These studies reveal an unexpected function for regulated intron retention in modulation of the timely expression of select transcripts during spermatogenesis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Global Analysis of miRNA-mRNA Interaction Network in Breast Cancer with Brain Metastasis.

PubMed

Li, Zhixin; Peng, Zhiqiang; Gu, Siyu; Zheng, Junfang; Feng, Duiping; Qin, Qiong; He, Junqi

2017-08-01

MicroRNAs (miRNAs) have been linked to a number of cancer types including breast cancer. The rate of brain metastases is 10-30% in patients with advanced breast cancer which is associated with poor prognosis. The potential application of miRNAs in the diagnostics and therapeutics of breast cancer with brain metastasis is an area of intense interest. In an initial effort to systematically address the differential expression of miRNAs and mRNAs in primary breast cancer which may provide clues for early detection of brain metastasis, we analyzed the consequent changes in global patterns of gene expression in Gene Expression Omnibus (GEO) data set obtained by microarray from patients with in situ carcinoma and patients with brain metastasis. The miRNA-pathway regulatory network and miRNA-mRNA regulatory network were investigated in breast cancer specimens from patients with brain metastasis to screen for significantly dysregulated miRNAs followed by prediction of their target genes and pathways by Gene Ontology (GO) analysis. Functional coordination of the changes of gene expression can be modulated by individual miRNAs. Two miRNAs, hsa-miR-17-5p and hsa-miR-16-5p, were identified as having the highest associations with targeted mRNAs [such as B-cell lymphoma 2 (BCL2), small body size/mothers against decapentaplegic 3 (SMAD3) and suppressor of cytokine signaling 1 (SOCS1)] and pathways associated with epithelial-mesenchymal transitions and other processes linked with cancer metastasis (including cell cycle, adherence junctions and extracellular matrix-receptor interaction). mRNAs for two genes [HECT, UBA and WWE domain containing 1 (HUWE1) and BCL2] were found to have the highest associations with miRNAs, which were down-regulated in brain metastasis specimens of breast cancer. The change of 11 selected miRNAs was verified in The Cancer Genome Atlas (TCGA) breast cancer dataset. Up-regulation of hsa-miR-17-5p was detected in triple-negative breast cancer tissues in TCGA. Furthermore, a negative correlation of hsa-miR-17-5p with overall survival and phosphatase and tensin homolog (PTEN) and BCL2 target genes was found in TCGA breast cancer specimens. Our findings provide a functionally coordinated expression pattern of different families of miRNAs that may have potential to provide clinicians with a strategy to treat breast cancer with brain metastasis from a systems-rather than a single-gene perspective. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Patterns of activity expressed by juvenile horseshoe crabs.

PubMed

Dubofsky, E A; Simpson, S D; Chabot, Christopher C; Watson, Winsor H

2013-09-01

Adult American horseshoe crabs, Limulus polyphemus, possess endogenous circadian and circatidal clocks controlling visual sensitivity and locomotion, respectively. The goal of this study was to determine the types of activity rhythms expressed by juvenile horseshoe crabs (n = 24) when exposed to a 14:10 light/dark cycle (LD) for 10 days, followed by 10 days of constant darkness (DD). Horseshoe crab activity was recorded with a digital time-lapse video system that used an infrared-sensitive camera so animals could be monitored at night. In LD, 15 animals expressed daily patterns of activity, 6 displayed a circatidal pattern, and the remaining 3 were arrhythmic. Of the 15 animals with daily patterns of locomotion, 7 had a significant preference (P < 0.05) for diurnal activity and 3 for nocturnal activity; the remainder did not express a significant preference for day or night activity. In DD, 13 horseshoe crabs expressed circatidal rhythms and 8 maintained a pattern of about 24 h. Although these results suggest the presence of a circadian clock influencing circatidal patterns of locomotion, these apparent circadian rhythms may actually represent the expression of just one of the two bouts of activity driven by the putative circalunidian clocks that control their tidal rhythms. Overall, these results indicate that, like adults, juvenile horseshoe crabs express both daily and tidal patterns of activity and that at least one, and maybe both, of these patterns is driven by endogenous clocks.

Biofilm Formation and Dispersal under the Influence of the Global Regulator CsrA of Escherichia coli

PubMed Central

Jackson, Debra W.; Suzuki, Kazushi; Oakford, Lawrence; Simecka, Jerry W.; Hart, Mark E.; Romeo, Tony

2002-01-01

The predominant mode of growth of bacteria in the environment is within sessile, matrix-enclosed communities known as biofilms. Biofilms often complicate chronic and difficult-to-treat infections by protecting bacteria from the immune system, decreasing antibiotic efficacy, and dispersing planktonic cells to distant body sites. While the biology of bacterial biofilms has become a major focus of microbial research, the regulatory mechanisms of biofilm development remain poorly defined and those of dispersal are unknown. Here we establish that the RNA binding global regulatory protein CsrA (carbon storage regulator) of Escherichia coli K-12 serves as both a repressor of biofilm formation and an activator of biofilm dispersal under a variety of culture conditions. Ectopic expression of the E. coli K-12 csrA gene repressed biofilm formation by related bacterial pathogens. A csrA knockout mutation enhanced biofilm formation in E. coli strains that were defective for extracellular, surface, or regulatory factors previously implicated in biofilm formation. In contrast, this csrA mutation did not affect biofilm formation by a glgA (glycogen synthase) knockout mutant. Complementation studies with glg genes provided further genetic evidence that the effects of CsrA on biofilm formation are mediated largely through the regulation of intracellular glycogen biosynthesis and catabolism. Finally, the expression of a chromosomally encoded csrA′-′lacZ translational fusion was dynamically regulated during biofilm formation in a pattern consistent with its role as a repressor. We propose that global regulation of central carbon flux by CsrA is an extremely important feature of E. coli biofilm development. PMID:11741870

Comparative transcriptome analysis reveals a global insight into molecular processes regulating citrate accumulation in sweet orange (Citrus sinensis).

PubMed

Lu, Xiaopeng; Cao, Xiongjun; Li, Feifei; Li, Jing; Xiong, Jiang; Long, Guiyou; Cao, Shangyin; Xie, Shenxi

2016-12-01

Citrate, the predominant organic acid in citrus, determines the taste of these fruits. However, little is known about the synergic molecular processes regulating citrate accumulation. Using 'Dahongtiancheng' (Citrus sinensis) and 'Bingtangcheng' (C. sinensis) with significant difference in citrate, the objectives of this study were to understand the global mechanisms of high-citrate accumulation in sweet orange. 'Dahongtiancheng' and 'Bingtangcheng' exhibit significantly different patterns in citrate accumulation throughout fruit development, with the largest differences observed at 50-70 days after full bloom (DAFB). Comparative transcriptome profiling was performed for the endocarps of both cultivars at 50 and 70 DAFB. Over 34.5 million clean reads per library were successfully mapped to the reference database and 670-2630 differentially expressed genes (DEGs) were found in four libraries. Among the genes, five transcription factors were ascertained to be the candidates regulating citrate accumulation. Functional assignments of the DEGs indicated that photosynthesis, the citrate cycle and amino acid metabolism were significantly altered in 'Dahongtiancheng'. Physiological and molecular analyses suggested that high photosynthetic efficiency and partial impairment of citrate catabolism were crucial for the high-citrate trait, and amino acid biosynthesis was one of the important directions for citrate flux. The results reveal a global insight into the gene expression changes in a high-citrate compared with a low-citrate sweet orange. High accumulating efficiency and impaired degradation of citrate may be associated with the high-citrate trait of 'Dahongtiancheng'. Findings in this study increase understanding of the molecular processes regulating citrate accumulation in sweet orange. © 2016 Scandinavian Plant Physiology Society.

Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain

PubMed Central

Montoya, Julio Cesar; Fajardo, Dianora; Peña, Angela; Sánchez, Adalberto; Domínguez, Martha C; Satizábal, José María

2014-01-01

Background: The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. Objective: To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. Methods: There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Results: Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously identified brain structures play a crucial role in the learning process, in different class of memory and in motor skills. Conclusion: The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition. PMID:25767303

Transcriptomic Insights into Phenological Development and Cold Tolerance of Wheat Grown in the Field1[OPEN

PubMed Central

Li, Qiang; Byrns, Brook; Badawi, Mohamed A.; Diallo, Abdoulaye Banire; Danyluk, Jean; Sarhan, Fathey; Zou, Jitao

2018-01-01

Cold acclimation and winter survival in cereal species is determined by complicated environmentally regulated gene expression. However, studies investigating these complex cold responses are mostly conducted in controlled environments that only consider the responses to single environmental variables. In this study, we have comprehensively profiled global transcriptional responses in crowns of field-grown spring and winter wheat (Triticum aestivum) genotypes and their near-isogenic lines with the VRN-A1 alleles swapped. This in-depth analysis revealed multiple signaling, interactive pathways that influence cold tolerance and phenological development to optimize plant growth and development in preparation for a wide range of over-winter stresses. Investigation of genetic differences at the VRN-A1 locus revealed that a vernalization requirement maintained a higher level of cold response pathways while VRN-A1 genetically promoted floral development. Our results also demonstrated the influence of genetic background on the expression of cold and flowering pathways. The link between delayed shoot apex development and the induction of cold tolerance was reflected by the gradual up-regulation of abscisic acid-dependent and C-REPEAT-BINDING FACTOR pathways. This was accompanied by the down-regulation of key genes involved in meristem development as the autumn progressed. The chromosome location of differentially expressed genes between the winter and spring wheat genetic backgrounds showed a striking pattern of biased gene expression on chromosomes 6A and 6D, indicating a transcriptional regulation at the genome level. This finding adds to the complexity of the genetic cascades and gene interactions that determine the evolutionary patterns of both phenological development and cold tolerance traits in wheat. PMID:29259104

The elephant shark methylome reveals conservation of epigenetic regulation across jawed vertebrates

PubMed Central

Peat, Julian R.; Ortega-Recalde, Oscar; Kardailsky, Olga; Hore, Timothy A.

2017-01-01

Background: Methylation of CG dinucleotides constitutes a critical system of epigenetic memory in bony vertebrates, where it modulates gene expression and suppresses transposon activity. The genomes of studied vertebrates are pervasively hypermethylated, with the exception of regulatory elements such as transcription start sites (TSSs), where the presence of methylation is associated with gene silencing. This system is not found in the sparsely methylated genomes of invertebrates, and establishing how it arose during early vertebrate evolution is impeded by a paucity of epigenetic data from basal vertebrates. Methods: We perform whole-genome bisulfite sequencing to generate the first genome-wide methylation profiles of a cartilaginous fish, the elephant shark Callorhinchus milii. Employing these to determine the elephant shark methylome structure and its relationship with expression, we compare this with higher vertebrates and an invertebrate chordate using published methylation and transcriptome data.  Results: Like higher vertebrates, the majority of elephant shark CG sites are highly methylated, and methylation is abundant across the genome rather than patterned in the mosaic configuration of invertebrates. This global hypermethylation includes transposable elements and the bodies of genes at all expression levels. Significantly, we document an inverse relationship between TSS methylation and expression in the elephant shark, supporting the presence of the repressive regulatory architecture shared by higher vertebrates. Conclusions: Our demonstration that methylation patterns in a cartilaginous fish are characteristic of higher vertebrates imply the conservation of this epigenetic modification system across jawed vertebrates separated by 465 million years of evolution. In addition, these findings position the elephant shark as a valuable model to explore the evolutionary history and function of vertebrate methylation. PMID:28580133

The elephant shark methylome reveals conservation of epigenetic regulation across jawed vertebrates.

PubMed

Peat, Julian R; Ortega-Recalde, Oscar; Kardailsky, Olga; Hore, Timothy A

2017-01-01

Methylation of CG dinucleotides constitutes a critical system of epigenetic memory in bony vertebrates, where it modulates gene expression and suppresses transposon activity. The genomes of studied vertebrates are pervasively hypermethylated, with the exception of regulatory elements such as transcription start sites (TSSs), where the presence of methylation is associated with gene silencing. This system is not found in the sparsely methylated genomes of invertebrates, and establishing how it arose during early vertebrate evolution is impeded by a paucity of epigenetic data from basal vertebrates.  We perform whole-genome bisulfite sequencing to generate the first genome-wide methylation profiles of a cartilaginous fish, the elephant shark Callorhinchus milii . Employing these to determine the elephant shark methylome structure and its relationship with expression, we compare this with higher vertebrates and an invertebrate chordate using published methylation and transcriptome data.  Results: Like higher vertebrates, the majority of elephant shark CG sites are highly methylated, and methylation is abundant across the genome rather than patterned in the mosaic configuration of invertebrates. This global hypermethylation includes transposable elements and the bodies of genes at all expression levels. Significantly, we document an inverse relationship between TSS methylation and expression in the elephant shark, supporting the presence of the repressive regulatory architecture shared by higher vertebrates.  Our demonstration that methylation patterns in a cartilaginous fish are characteristic of higher vertebrates imply the conservation of this epigenetic modification system across jawed vertebrates separated by 465 million years of evolution. In addition, these findings position the elephant shark as a valuable model to explore the evolutionary history and function of vertebrate methylation.

The impact of half-a-degree Celsius upon the spatial pattern of future sea-level change.

NASA Astrophysics Data System (ADS)

Jackson, Luke

2017-04-01

It has been shown that the global thermal expansion of sea level and ocean dynamics are linearly related to global temperature change. On this basis one can estimate the difference in local sea-level change between a 1.5°C and 2.0°C world. The mitigation scenario RCP 2.6 shows an end-of-century global temperature range of 0.9 to 2.3°C (median 1.6°C). Additional sea-level components, such as mass changes in ice sheets, glaciers and land-water storage have unique spatial patterns that contribute to sea-level change and will be indirectly affected by global temperature change. We project local sea-level change for RCP 2.6 using sub-sets of models in the CMIP5 archive that follow different global temperature pathways. The method used to calculate local sea-level change is probabilistic and combines the normalised spatial patterns of sea-level components with global average projections of individual sea-level components.

Global Simulation of Aviation Operations

NASA Technical Reports Server (NTRS)

Sridhar, Banavar; Sheth, Kapil; Ng, Hok Kwan; Morando, Alex; Li, Jinhua

2016-01-01

The simulation and analysis of global air traffic is limited due to a lack of simulation tools and the difficulty in accessing data sources. This paper provides a global simulation of aviation operations combining flight plans and real air traffic data with historical commercial city-pair aircraft type and schedule data and global atmospheric data. The resulting capability extends the simulation and optimization functions of NASA's Future Air Traffic Management Concept Evaluation Tool (FACET) to global scale. This new capability is used to present results on the evolution of global air traffic patterns from a concentration of traffic inside US, Europe and across the Atlantic Ocean to a more diverse traffic pattern across the globe with accelerated growth in Asia, Australia, Africa and South America. The simulation analyzes seasonal variation in the long-haul wind-optimal traffic patterns in six major regions of the world and provides potential time-savings of wind-optimal routes compared with either great circle routes or current flight-plans if available.

A framework for analyzing the relationship between gene expression and morphological, topological, and dynamical patterns in neuronal networks.

PubMed

de Arruda, Henrique Ferraz; Comin, Cesar Henrique; Miazaki, Mauro; Viana, Matheus Palhares; Costa, Luciano da Fontoura

2015-04-30

A key point in developmental biology is to understand how gene expression influences the morphological and dynamical patterns that are observed in living beings. In this work we propose a methodology capable of addressing this problem that is based on estimating the mutual information and Pearson correlation between the intensity of gene expression and measurements of several morphological properties of the cells. A similar approach is applied in order to identify effects of gene expression over the system dynamics. Neuronal networks were artificially grown over a lattice by considering a reference model used to generate artificial neurons. The input parameters of the artificial neurons were determined according to two distinct patterns of gene expression and the dynamical response was assessed by considering the integrate-and-fire model. As far as single gene dependence is concerned, we found that the interaction between the gene expression and the network topology, as well as between the former and the dynamics response, is strongly affected by the gene expression pattern. In addition, we observed a high correlation between the gene expression and some topological measurements of the neuronal network for particular patterns of gene expression. To our best understanding, there are no similar analyses to compare with. A proper understanding of gene expression influence requires jointly studying the morphology, topology, and dynamics of neurons. The proposed framework represents a first step towards predicting gene expression patterns from morphology and connectivity. Copyright © 2015. Published by Elsevier B.V.

Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjögren's syndrome.

PubMed

Gottenberg, Jacques-Eric; Cagnard, Nicolas; Lucchesi, Carlo; Letourneur, Franck; Mistou, Sylvie; Lazure, Thierry; Jacques, Sebastien; Ba, Nathalie; Ittah, Marc; Lepajolec, Christine; Labetoulle, Marc; Ardizzone, Marc; Sibilia, Jean; Fournier, Catherine; Chiocchia, Gilles; Mariette, Xavier

2006-02-21

Gene expression analysis of target organs might help provide new insights into the pathogenesis of autoimmune diseases. We used global gene expression profiling of minor salivary glands to identify patterns of gene expression in patients with primary Sjögren's syndrome (pSS), a common and prototypic systemic autoimmune disease. Gene expression analysis allowed for differentiating most patients with pSS from controls. The expression of 23 genes in the IFN pathways, including two Toll-like receptors (TLR8 and TLR9), was significantly different between patients and controls. Furthermore, the increased expression of IFN-inducible genes, BAFF and IFN-induced transmembrane protein 1, was also demonstrated in ocular epithelial cells by quantitative RT-PCR. In vitro activation showed that these genes were effectively modulated by IFNs in salivary gland epithelial cells, the target cells of autoimmunity in pSS. The activation of IFN pathways led us to investigate whether plasmacytoid dendritic cells were recruited in salivary glands. These IFN-producing cells were detected by immunohistochemistry in all patients with pSS, whereas none was observed in controls. In conclusion, our results support the pathogenic interaction between the innate and adaptive immune system in pSS. The persistence of the IFN signature might be related to a vicious circle, in which the environment interacts with genetic factors to drive the stimulation of salivary TLRs.

Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjögren’s syndrome

PubMed Central

Gottenberg, Jacques-Eric; Cagnard, Nicolas; Lucchesi, Carlo; Letourneur, Franck; Mistou, Sylvie; Lazure, Thierry; Jacques, Sebastien; Ba, Nathalie; Ittah, Marc; Lepajolec, Christine; Labetoulle, Marc; Ardizzone, Marc; Sibilia, Jean; Fournier, Catherine; Chiocchia, Gilles; Mariette, Xavier

2006-01-01

Gene expression analysis of target organs might help provide new insights into the pathogenesis of autoimmune diseases. We used global gene expression profiling of minor salivary glands to identify patterns of gene expression in patients with primary Sjögren’s syndrome (pSS), a common and prototypic systemic autoimmune disease. Gene expression analysis allowed for differentiating most patients with pSS from controls. The expression of 23 genes in the IFN pathways, including two Toll-like receptors (TLR8 and TLR9), was significantly different between patients and controls. Furthermore, the increased expression of IFN-inducible genes, BAFF and IFN-induced transmembrane protein 1, was also demonstrated in ocular epithelial cells by quantitative RT-PCR. In vitro activation showed that these genes were effectively modulated by IFNs in salivary gland epithelial cells, the target cells of autoimmunity in pSS. The activation of IFN pathways led us to investigate whether plasmacytoid dendritic cells were recruited in salivary glands. These IFN-producing cells were detected by immunohistochemistry in all patients with pSS, whereas none was observed in controls. In conclusion, our results support the pathogenic interaction between the innate and adaptive immune system in pSS. The persistence of the IFN signature might be related to a vicious circle, in which the environment interacts with genetic factors to drive the stimulation of salivary TLRs. PMID:16477017

Cloud-scale genomic signals processing classification analysis for gene expression microarray data.

PubMed

Harvey, Benjamin; Soo-Yeon Ji

2014-01-01

As microarray data available to scientists continues to increase in size and complexity, it has become overwhelmingly important to find multiple ways to bring inference though analysis of DNA/mRNA sequence data that is useful to scientists. Though there have been many attempts to elucidate the issue of bringing forth biological inference by means of wavelet preprocessing and classification, there has not been a research effort that focuses on a cloud-scale classification analysis of microarray data using Wavelet thresholding in a Cloud environment to identify significantly expressed features. This paper proposes a novel methodology that uses Wavelet based Denoising to initialize a threshold for determination of significantly expressed genes for classification. Additionally, this research was implemented and encompassed within cloud-based distributed processing environment. The utilization of Cloud computing and Wavelet thresholding was used for the classification 14 tumor classes from the Global Cancer Map (GCM). The results proved to be more accurate than using a predefined p-value for differential expression classification. This novel methodology analyzed Wavelet based threshold features of gene expression in a Cloud environment, furthermore classifying the expression of samples by analyzing gene patterns, which inform us of biological processes. Moreover, enabling researchers to face the present and forthcoming challenges that may arise in the analysis of data in functional genomics of large microarray datasets.

AutA and AutR, Two Novel Global Transcriptional Regulators, Facilitate Avian Pathogenic Escherichia coli Infection.

PubMed

Zhuge, Xiangkai; Tang, Fang; Zhu, Hongfei; Mao, Xiang; Wang, Shaohui; Wu, Zongfu; Lu, Chengping; Dai, Jianjun; Fan, Hongjie

2016-04-26

Bacteria can change its lifestyle during inhabiting in host niches where they survive and replicate by rapidly altering gene expression pattern to accommodate the new environment. In this study, two novel regulators in avian pathogenic Escherichia coli (APEC) were identified and designated as AutA and AutR. RT-PCR and β-galactosidase assay results showed that AutA and AutR co-regulated the expression of adhesin UpaB in APEC strain DE205B. Electrophoretic mobility shift assay showed that AutA and AutR could directly bind the upaB promoter DNA. In vitro transcription assay indicated that AutA could activate the upaB transcription, while AutR inhibited the upaB transcription due to directly suppressing the activating effect of AutA on UpaB expression. Transcriptome analysis showed that AutA and AutR coherently affected the expression of hundreds of genes. Our study confirmed that AutA and AutR co-regulated the expression of DE205B K1 capsule and acid resistance systems in E. coli acid fitness island (AFI). Moreover, phenotypic heterogeneity in expression of K1 capsule and acid resistance systems in AFI during host-pathogen interaction was associated with the regulation of AutA and AutR. Collectively speaking, our studies presented that AutA and AutR are involved in APEC adaptive lifestyle change to facilitate its infection.

Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature.

PubMed

Haberman, Yael; Tickle, Timothy L; Dexheimer, Phillip J; Kim, Mi-Ok; Tang, Dora; Karns, Rebekah; Baldassano, Robert N; Noe, Joshua D; Rosh, Joel; Markowitz, James; Heyman, Melvin B; Griffiths, Anne M; Crandall, Wallace V; Mack, David R; Baker, Susan S; Huttenhower, Curtis; Keljo, David J; Hyams, Jeffrey S; Kugathasan, Subra; Walters, Thomas D; Aronow, Bruce; Xavier, Ramnik J; Gevers, Dirk; Denson, Lee A

2014-08-01

Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches.

ASSESSING THE ROLE OF CASPASE ACTIVITY AND METACASPASE EXPRESSION ON VIRAL SUSCEPTIBILITY OF THE COCCOLITHOPHORE, EMILIANIA HUXLEYI (HAPTOPHYTA).

PubMed

Bidle, Kay D; Kwityn, Clifford J

2012-10-01

As part of their strategy to infect the globally important coccolithophore, Emiliania huxleyi (Lohmann) W.W. Hay & H.P. Mohler, Coccolithoviruses trigger and regulate the host's programmed cell death (PCD) machinery during lytic infection. The induction and recruitment of host metacaspases, specialized, ancestral death proteases that facilitate viral lysis, suggests they may be important subcellular determinants to infection. We examined the "basal" levels and patterns of caspase activity and metacaspase expression in exponentially growing resistant and sensitive E. huxleyi strains and linked them with susceptibility to E. huxleyi virus 1 (EhV1). Resistant E. huxleyi strains were consistently characterized by low caspase specific activity and a relatively simple metacaspase expression profile. In contrast, sensitive E. huxleyi strains had markedly elevated caspase specific activity and consistently expressed more diverse metacaspase proteins. Using pooled data sets from triplicate experiments, we observed statistically significant linear correlations between infectivity, caspase activity, and metacaspase expression, with each strain forming distinct clusters, within a gradient in viral susceptibility. At the same time, we observed positive correlations between the expression of a subset of metacaspase proteins and lower susceptibility, suggestive of potential protective roles. Our findings implicate the importance of subtle differences in the basal physiological regulation of the PCD machinery to viral resistance or sensitivity and cell fate. © 2012 Phycological Society of America.

Morphological Characters and Transcriptome Profiles Associated with Black Skin and Red Skin in Crimson Snapper (Lutjanus erythropterus)

PubMed Central

Zhang, Yan-Ping; Wang, Zhong-Duo; Guo, Yu-Song; Liu, Li; Yu, Juan; Zhang, Shun; Liu, Shao-Jun; Liu, Chu-Wu

2015-01-01

In this study, morphology observation and illumina sequencing were performed on two different coloration skins of crimson snapper (Lutjanus erythropterus), the black zone and the red zone. Three types of chromatophores, melanophores, iridophores and xanthophores, were organized in the skins. The main differences between the two colorations were in the amount and distribution of the three chromatophores. After comparing the two transcriptomes, 9200 unigenes with significantly different expressions (ratio change ≥ 2 and q-value ≤ 0.05) were found, of which 5972 were up-regulated in black skin and 3228 were up-regulated in red skin. Through the function annotation, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the differentially transcribed genes, we excavated a number of uncharacterized candidate pigment genes as well as found the conserved genes affecting pigmentation in crimson snapper. The patterns of expression of 14 pigment genes were confirmed by the Quantitative real-time PCR analysis between the two color skins. Overall, this study shows a global survey of the morphological characters and transcriptome analysis of the different coloration skins in crimson snapper, and provides valuable cellular and genetic information to uncover the mechanism of the formation of pigment patterns in snappers. PMID:26569232

Morphological Characters and Transcriptome Profiles Associated with Black Skin and Red Skin in Crimson Snapper (Lutjanus erythropterus).

PubMed

Zhang, Yan-Ping; Wang, Zhong-Duo; Guo, Yu-Song; Liu, Li; Yu, Juan; Zhang, Shun; Liu, Shao-Jun; Liu, Chu-Wu

2015-11-12

In this study, morphology observation and illumina sequencing were performed on two different coloration skins of crimson snapper (Lutjanus erythropterus), the black zone and the red zone. Three types of chromatophores, melanophores, iridophores and xanthophores, were organized in the skins. The main differences between the two colorations were in the amount and distribution of the three chromatophores. After comparing the two transcriptomes, 9200 unigenes with significantly different expressions (ratio change ≥ 2 and q-value ≤ 0.05) were found, of which 5972 were up-regulated in black skin and 3228 were up-regulated in red skin. Through the function annotation, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the differentially transcribed genes, we excavated a number of uncharacterized candidate pigment genes as well as found the conserved genes affecting pigmentation in crimson snapper. The patterns of expression of 14 pigment genes were confirmed by the Quantitative real-time PCR analysis between the two color skins. Overall, this study shows a global survey of the morphological characters and transcriptome analysis of the different coloration skins in crimson snapper, and provides valuable cellular and genetic information to uncover the mechanism of the formation of pigment patterns in snappers.

Perception of shapes targeting local and global processes in autism spectrum disorders.

PubMed

Grinter, Emma J; Maybery, Murray T; Pellicano, Elizabeth; Badcock, Johanna C; Badcock, David R

2010-06-01

Several researchers have found evidence for impaired global processing in the dorsal visual stream in individuals with autism spectrum disorders (ASDs). However, support for a similar pattern of visual processing in the ventral visual stream is less consistent. Critical to resolving the inconsistency is the assessment of local and global form processing ability. Within the visual domain, radial frequency (RF) patterns - shapes formed by sinusoidally varying the radius of a circle to add 'bumps' of a certain number to a circle - can be used to examine local and global form perception. Typically developing children and children with an ASD discriminated between circles and RF patterns that are processed either locally (RF24) or globally (RF3). Children with an ASD required greater shape deformation to identify RF3 shapes compared to typically developing children, consistent with difficulty in global processing in the ventral stream. No group difference was observed for RF24 shapes, suggesting intact local ventral-stream processing. These outcomes support the position that a deficit in global visual processing is present in ASDs, consistent with the notion of Weak Central Coherence.

Arabidopsis Gene Family Profiler (aGFP)--user-oriented transcriptomic database with easy-to-use graphic interface.

PubMed

Dupl'áková, Nikoleta; Renák, David; Hovanec, Patrik; Honysová, Barbora; Twell, David; Honys, David

2007-07-23

Microarray technologies now belong to the standard functional genomics toolbox and have undergone massive development leading to increased genome coverage, accuracy and reliability. The number of experiments exploiting microarray technology has markedly increased in recent years. In parallel with the rapid accumulation of transcriptomic data, on-line analysis tools are being introduced to simplify their use. Global statistical data analysis methods contribute to the development of overall concepts about gene expression patterns and to query and compose working hypotheses. More recently, these applications are being supplemented with more specialized products offering visualization and specific data mining tools. We present a curated gene family-oriented gene expression database, Arabidopsis Gene Family Profiler (aGFP; http://agfp.ueb.cas.cz), which gives the user access to a large collection of normalised Affymetrix ATH1 microarray datasets. The database currently contains NASC Array and AtGenExpress transcriptomic datasets for various tissues at different developmental stages of wild type plants gathered from nearly 350 gene chips. The Arabidopsis GFP database has been designed as an easy-to-use tool for users needing an easily accessible resource for expression data of single genes, pre-defined gene families or custom gene sets, with the further possibility of keyword search. Arabidopsis Gene Family Profiler presents a user-friendly web interface using both graphic and text output. Data are stored at the MySQL server and individual queries are created in PHP script. The most distinguishable features of Arabidopsis Gene Family Profiler database are: 1) the presentation of normalized datasets (Affymetrix MAS algorithm and calculation of model-based gene-expression values based on the Perfect Match-only model); 2) the choice between two different normalization algorithms (Affymetrix MAS4 or MAS5 algorithms); 3) an intuitive interface; 4) an interactive "virtual plant" visualizing the spatial and developmental expression profiles of both gene families and individual genes. Arabidopsis GFP gives users the possibility to analyze current Arabidopsis developmental transcriptomic data starting with simple global queries that can be expanded and further refined to visualize comparative and highly selective gene expression profiles.

Increasing occurrence of cold and warm extremes during the recent global warming slowdown.

PubMed

Johnson, Nathaniel C; Xie, Shang-Ping; Kosaka, Yu; Li, Xichen

2018-04-30

The recent levelling of global mean temperatures after the late 1990s, the so-called global warming hiatus or slowdown, ignited a surge of scientific interest into natural global mean surface temperature variability, observed temperature biases, and climate communication, but many questions remain about how these findings relate to variations in more societally relevant temperature extremes. Here we show that both summertime warm and wintertime cold extreme occurrences increased over land during the so-called hiatus period, and that these increases occurred for distinct reasons. The increase in cold extremes is associated with an atmospheric circulation pattern resembling the warm Arctic-cold continents pattern, whereas the increase in warm extremes is tied to a pattern of sea surface temperatures resembling the Atlantic Multidecadal Oscillation. These findings indicate that large-scale factors responsible for the most societally relevant temperature variations over continents are distinct from those of global mean surface temperature.

Global bioethics -- myth or reality?

PubMed

Holm, Søren; Williams-Jones, Bryn

2006-09-11

There has been debate on whether a global or unified field of bioethics exists. If bioethics is a unified global field, or at the very least a closely shared way of thinking, then we should expect bioethicists to behave the same way in their academic activities anywhere in the world. This paper investigates whether there is a 'global bioethics' in the sense of a unified academic community. To address this question, we study the web-linking patterns of bioethics institutions, the citation patterns of bioethics papers and the buying patterns of bioethics books. All three analyses indicate that there are geographical and institutional differences in the academic behavior of bioethicists and bioethics institutions. These exploratory studies support the position that there is no unified global field of bioethics. This is a problem if the only reason is parochialism. But these regional differences are probably of less concern if one notices that bioethics comes in many not always mutually understandable dialects.

Delayed hippocampal neuronal death in young gerbil following transient global cerebral ischemia is related to higher and longer-term expression of p63 in the ischemic hippocampus

PubMed Central

Bae, Eun Joo; Chen, Bai Hui; Yan, Bing Chun; Shin, Bich Na; Cho, Jeong Hwi; Kim, In Hye; Ahn, Ji Hyeon; Lee, Jae Chul; Tae, Hyun-Jin; Hong, Seongkweon; Kim, Dong Won; Cho, Jun Hwi; Lee, Yun Lyul; Won, Moo-Ho; Park, Joon Ha

2015-01-01

The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions (CA1–3) between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia. p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group. p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults. PMID:26199612

Copper induces expression and methylation changes of early development genes in Crassostrea gigas embryos.

PubMed

Sussarellu, Rossana; Lebreton, Morgane; Rouxel, Julien; Akcha, Farida; Rivière, Guillaume

2018-03-01

Copper contamination is widespread along coastal areas and exerts adverse effects on marine organisms such as mollusks. In the Pacific oyster, copper induces severe developmental abnormalities during early life stages; however, the underlying molecular mechanisms are largely unknown. This study aims to better understand whether the embryotoxic effects of copper in Crassostrea gigas could be mediated by alterations in gene expression, and the putative role of DNA methylation, which is known to contribute to gene regulation in early embryo development. For that purpose, oyster embryos were exposed to 4 nominal copper concentrations (0.1, 1, 10 and 20 μg L -1 Cu 2+ ) during early development assays. Embryotoxicity was monitored through the oyster embryo-larval bioassay at the D-larva stage 24 h post fertilization (hpf) and genotoxicity at gastrulation 7 hpf. In parallel, the relative expression of 15 genes encoding putative homeotic, biomineralization and DNA methylation proteins was measured at three developmental stages (3 hpf morula stage, 7 hpf gastrula stage, 24 hpf D-larvae stage) using RT-qPCR. Global DNA content in methylcytosine and hydroxymethylcytosine were measured by HPLC and gene-specific DNA methylation levels were monitored using MeDIP-qPCR. A significant increase in larval abnormalities was observed from copper concentrations of 10 μg L -1 , while significant genotoxic effects were detected at 1 μg L -1 and above. All the selected genes presented a stage-dependent expression pattern, which was impaired for some homeobox and DNA methylation genes (Notochord, HOXA1, HOX2, Lox5, DNMT3b and CXXC-1) after copper exposure. While global DNA methylation (5-methylcytosine) at gastrula stage didn't show significant changes between experimental conditions, 5-hydroxymethylcytosine, its degradation product, decreased upon copper treatment. The DNA methylation of exons and the transcript levels were correlated in control samples for HOXA1 but such a correlation was diminished following copper exposure. The methylation level of some specific gene regions (HoxA1, Hox2, Engrailed2 and Notochord) displayed changes upon copper exposure. Such changes were gene and exon-specific and no obvious global trends could be identified. Our study suggests that the embryotoxic effects of copper in oysters could involve homeotic gene expression impairment possibly by changing DNA methylation levels. Copyright © 2018 Elsevier B.V. All rights reserved.

Quantitative expression analysis of selected transcription factors in pavement, basal and trichome cells of mature leaves from Arabidopsis thaliana

PubMed Central

Schliep, Martin; Ebert, Berit; Simon-Rosin, Ulrike; Zoeller, Daniela

2010-01-01

Gene expression levels of several transcription factors from Arabidopsis thaliana that were described previously to be involved in leaf development and trichome formation were analysed in trichome, basal and pavement cells of mature leaves. Single cell samples of these three cells types were collected by glass micro-capillaries. Real-time reverse transcription (RT)-PCR was used to analyse expression patterns of the following transcription factors: MYB23, MYB55, AtHB1, FILAMENTOUS FLOWER (FIL)/YABBY1 (YAB1), TRIPTYCHON (TRY) and CAPRICE (CPC). A difference in the expression patterns of TRY and CPC was revealed. Contrary to the CPC expression pattern, no transcripts of TRY could be detected in pavement cells. FIL/YAB1 was exclusively expressed in trichome cells. AtHB1 was highly expressed throughout all three cell types. MYB55 was higher expressed in basal cells than in trichome and pavement cells. MYB23 showed a pattern of low expression in pavement cells, medium in basal cells and high expression in trichomes. Expression patterns obtained by single cell sampling and real-time RT-PCR were compared to promoter GUS fusions of the selected transcription factors. Therefore, we regenerated two transgenic Arabidopsis lines that expressed the GUS reporter gene under control of the promoters of MYB55 and YAB1. In conclusion, despite their function in leaf morphogenesis, all six transcription factors were detected in mature leaves. Furthermore, single cell sampling and promoter GUS staining patterns demonstrated the predominant presence of MYB55 in basal cells as compared to pavement cells and trichomes. PMID:20101514

Quantitative expression analysis of selected transcription factors in pavement, basal and trichome cells of mature leaves from Arabidopsis thaliana.

PubMed

Schliep, Martin; Ebert, Berit; Simon-Rosin, Ulrike; Zoeller, Daniela; Fisahn, Joachim

2010-05-01

Gene expression levels of several transcription factors from Arabidopsis thaliana that were described previously to be involved in leaf development and trichome formation were analysed in trichome, basal and pavement cells of mature leaves. Single cell samples of these three cells types were collected by glass micro-capillaries. Real-time reverse transcription (RT)-PCR was used to analyse expression patterns of the following transcription factors: MYB23, MYB55, AtHB1, FILAMENTOUS FLOWER (FIL)/YABBY1 (YAB1), TRIPTYCHON (TRY) and CAPRICE (CPC). A difference in the expression patterns of TRY and CPC was revealed. Contrary to the CPC expression pattern, no transcripts of TRY could be detected in pavement cells. FIL/YAB1 was exclusively expressed in trichome cells. AtHB1 was highly expressed throughout all three cell types. MYB55 was higher expressed in basal cells than in trichome and pavement cells. MYB23 showed a pattern of low expression in pavement cells, medium in basal cells and high expression in trichomes. Expression patterns obtained by single cell sampling and real-time RT-PCR were compared to promoter GUS fusions of the selected transcription factors. Therefore, we regenerated two transgenic Arabidopsis lines that expressed the GUS reporter gene under control of the promoters of MYB55 and YAB1. In conclusion, despite their function in leaf morphogenesis, all six transcription factors were detected in mature leaves. Furthermore, single cell sampling and promoter GUS staining patterns demonstrated the predominant presence of MYB55 in basal cells as compared to pavement cells and trichomes.

Function does not follow form in gene regulatory circuits.

PubMed

Payne, Joshua L; Wagner, Andreas

2015-08-20

Gene regulatory circuits are to the cell what arithmetic logic units are to the chip: fundamental components of information processing that map an input onto an output. Gene regulatory circuits come in many different forms, distinct structural configurations that determine who regulates whom. Studies that have focused on the gene expression patterns (functions) of circuits with a given structure (form) have examined just a few structures or gene expression patterns. Here, we use a computational model to exhaustively characterize the gene expression patterns of nearly 17 million three-gene circuits in order to systematically explore the relationship between circuit form and function. Three main conclusions emerge. First, function does not follow form. A circuit of any one structure can have between twelve and nearly thirty thousand distinct gene expression patterns. Second, and conversely, form does not follow function. Most gene expression patterns can be realized by more than one circuit structure. And third, multifunctionality severely constrains circuit form. The number of circuit structures able to drive multiple gene expression patterns decreases rapidly with the number of these patterns. These results indicate that it is generally not possible to infer circuit function from circuit form, or vice versa.

Discovering high-resolution patterns of differential DNA methylation that correlate with gene expression changes

PubMed Central

VanderKraats, Nathan D.; Hiken, Jeffrey F.; Decker, Keith F.; Edwards, John R.

2013-01-01

Methylation of the CpG-rich region (CpG island) overlapping a gene’s promoter is a generally accepted mechanism for silencing expression. While recent technological advances have enabled measurement of DNA methylation and expression changes genome-wide, only modest correlations between differential methylation at gene promoters and expression have been found. We hypothesize that stronger associations are not observed because existing analysis methods oversimplify their representation of the data and do not capture the diversity of existing methylation patterns. Recently, other patterns such as CpG island shore methylation and long partially hypomethylated domains have also been linked with gene silencing. Here, we detail a new approach for discovering differential methylation patterns associated with expression change using genome-wide high-resolution methylation data: we represent differential methylation as an interpolated curve, or signature, and then identify groups of genes with similarly shaped signatures and corresponding expression changes. Our technique uncovers a diverse set of patterns that are conserved across embryonic stem cell and cancer data sets. Overall, we find strong associations between these methylation patterns and expression. We further show that an extension of our method also outperforms other approaches by generating a longer list of genes with higher quality associations between differential methylation and expression. PMID:23748561

Global biogeography of human infectious diseases.

PubMed

Murray, Kris A; Preston, Nicholas; Allen, Toph; Zambrana-Torrelio, Carlos; Hosseini, Parviez R; Daszak, Peter

2015-10-13

The distributions of most infectious agents causing disease in humans are poorly resolved or unknown. However, poorly known and unknown agents contribute to the global burden of disease and will underlie many future disease risks. Existing patterns of infectious disease co-occurrence could thus play a critical role in resolving or anticipating current and future disease threats. We analyzed the global occurrence patterns of 187 human infectious diseases across 225 countries and seven epidemiological classes (human-specific, zoonotic, vector-borne, non-vector-borne, bacterial, viral, and parasitic) to show that human infectious diseases exhibit distinct spatial grouping patterns at a global scale. We demonstrate, using outbreaks of Ebola virus as a test case, that this spatial structuring provides an untapped source of prior information that could be used to tighten the focus of a range of health-related research and management activities at early stages or in data-poor settings, including disease surveillance, outbreak responses, or optimizing pathogen discovery. In examining the correlates of these spatial patterns, among a range of geographic, epidemiological, environmental, and social factors, mammalian biodiversity was the strongest predictor of infectious disease co-occurrence overall and for six of the seven disease classes examined, giving rise to a striking congruence between global pathogeographic and "Wallacean" zoogeographic patterns. This clear biogeographic signal suggests that infectious disease assemblages remain fundamentally constrained in their distributions by ecological barriers to dispersal or establishment, despite the homogenizing forces of globalization. Pathogeography thus provides an overarching context in which other factors promoting infectious disease emergence and spread are set.

Climatic change and wildland recreation: Examining the changing patterns of wilderness recreation in response to the effects of global climate change and the El Nino phenomenon

Treesearch

Vinod Sasidharan

2000-01-01

Impacts of global climate change on the biophysical components of wilderness areas have the potential to alter their recreational utility of wilderness areas. Concomitantly, the frequency and patterns of both land-based and water-based wilderness recreation activities will be affected. Despite the difficulty of responding to the unclear dimensions of global climate...

Structural salience and the nonaccidentality of a Gestalt.

PubMed

Strother, Lars; Kubovy, Michael

2012-08-01

We perceive structure through a process of perceptual organization. Here we report a new perceptual organization phenomenon-the facilitation of visual grouping by global curvature. Observers viewed patterns that they perceived as organized into collections of curves. The patterns were perceptually ambiguous such that the perceived orientation of the patterns varied from trial to trial. When patterns were sufficiently dense and proximity was equated for the predominant perceptual alternatives, observers tended to perceive the organization with the greatest curvature. This effect is tantamount to visual grouping by maximal curvature and thus demonstrates an unprecedented effect of global structure on perceptual organization. We account for this result with a model that predicts the perceived organization of a pattern as function of its nonaccidentality, which we define as the probability that it could have occurred by chance. Our findings demonstrate a novel relationship between the geometry of a pattern and the visual salience of global structure. (c) 2012 APA, all rights reserved.

Challenges for modeling global gene regulatory networks during development: insights from Drosophila.

PubMed

Wilczynski, Bartek; Furlong, Eileen E M

2010-04-15

Development is regulated by dynamic patterns of gene expression, which are orchestrated through the action of complex gene regulatory networks (GRNs). Substantial progress has been made in modeling transcriptional regulation in recent years, including qualitative "coarse-grain" models operating at the gene level to very "fine-grain" quantitative models operating at the biophysical "transcription factor-DNA level". Recent advances in genome-wide studies have revealed an enormous increase in the size and complexity or GRNs. Even relatively simple developmental processes can involve hundreds of regulatory molecules, with extensive interconnectivity and cooperative regulation. This leads to an explosion in the number of regulatory functions, effectively impeding Boolean-based qualitative modeling approaches. At the same time, the lack of information on the biophysical properties for the majority of transcription factors within a global network restricts quantitative approaches. In this review, we explore the current challenges in moving from modeling medium scale well-characterized networks to more poorly characterized global networks. We suggest to integrate coarse- and find-grain approaches to model gene regulatory networks in cis. We focus on two very well-studied examples from Drosophila, which likely represent typical developmental regulatory modules across metazoans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Pathogenic Influenza Viruses and Coronaviruses Utilize Similar and Contrasting Approaches To Control Interferon-Stimulated Gene Responses

PubMed Central

Menachery, Vineet D.; Eisfeld, Amie J.; Schäfer, Alexandra; Josset, Laurence; Sims, Amy C.; Proll, Sean; Fan, Shufang; Li, Chengjun; Neumann, Gabriele; Tilton, Susan C.; Chang, Jean; Gralinski, Lisa E.; Long, Casey; Green, Richard; Williams, Christopher M.; Weiss, Jeffrey; Matzke, Melissa M.; Webb-Robertson, Bobbie-Jo; Schepmoes, Athena A.; Shukla, Anil K.; Metz, Thomas O.; Smith, Richard D.; Waters, Katrina M.; Katze, Michael G.; Kawaoka, Yoshihiro

2014-01-01

ABSTRACT The broad range and diversity of interferon-stimulated genes (ISGs) function to induce an antiviral state within the host, impeding viral pathogenesis. While successful respiratory viruses overcome individual ISG effectors, analysis of the global ISG response and subsequent viral antagonism has yet to be examined. Employing models of the human airway, transcriptomics and proteomics datasets were used to compare ISG response patterns following highly pathogenic H5N1 avian influenza (HPAI) A virus, 2009 pandemic H1N1, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome CoV (MERS-CoV) infection. The results illustrated distinct approaches utilized by each virus to antagonize the global ISG response. In addition, the data revealed that highly virulent HPAI virus and MERS-CoV induce repressive histone modifications, which downregulate expression of ISG subsets. Notably, influenza A virus NS1 appears to play a central role in this histone-mediated downregulation in highly pathogenic influenza strains. Together, the work demonstrates the existence of unique and common viral strategies for controlling the global ISG response and provides a novel avenue for viral antagonism via altered histone modifications. PMID:24846384

Control strategies of 3-cell Central Pattern Generator via global stimuli

NASA Astrophysics Data System (ADS)

Lozano, Álvaro; Rodríguez, Marcos; Barrio, Roberto

2016-03-01

The study of the synchronization patterns of small neuron networks that control several biological processes has become an interesting growing discipline. Some of these synchronization patterns of individual neurons are related to some undesirable neurological diseases, and they are believed to play a crucial role in the emergence of pathological rhythmic brain activity in different diseases, like Parkinson’s disease. We show how, with a suitable combination of short and weak global inhibitory and excitatory stimuli over the whole network, we can switch between different stable bursting patterns in small neuron networks (in our case a 3-neuron network). We develop a systematic study showing and explaining the effects of applying the pulses at different moments. Moreover, we compare the technique on a completely symmetric network and on a slightly perturbed one (a much more realistic situation). The present approach of using global stimuli may allow to avoid undesirable synchronization patterns with nonaggressive stimuli.

A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration.

PubMed

Kuttippurathu, Lakshmi; Patra, Biswanath; Hoek, Jan B; Vadigepalli, Rajanikanth

2016-03-01

Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze the genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to the regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1 h post PHx. This set was associated with the regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1 h binding targets showed ethanol-specific differential expression through 6 h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx.

Epigenetic regulation of serotype expression antagonizes transcriptome dynamics in Paramecium tetraurelia

PubMed Central

Cheaib, Miriam; Dehghani Amirabad, Azim; Nordström, Karl J. V.; Schulz, Marcel H.; Simon, Martin

2015-01-01

Phenotypic variation of a single genotype is achieved by alterations in gene expression patterns. Regulation of such alterations depends on their time scale, where short-time adaptations differ from permanently established gene expression patterns maintained by epigenetic mechanisms. In the ciliate Paramecium, serotypes were described for an epigenetically controlled gene expression pattern of an individual multigene family. Paradoxically, individual serotypes can be triggered in Paramecium by alternating environments but are then stabilized by epigenetic mechanisms, thus raising the question to which extend their expression follows environmental stimuli. To characterize environmental adaptation in the context of epigenetically controlled serotype expression, we used RNA-seq to characterize transcriptomes of serotype pure cultures. The resulting vegetative transcriptome resource is first analysed for genes involved in the adaptive response to the altered environment. Secondly, we identified groups of genes that do not follow the adaptive response but show co-regulation with the epigenetically controlled serotype system, suggesting that their gene expression pattern becomes manifested by similar mechanisms. In our experimental set-up, serotype expression and the entire group of co-regulated genes were stable among environmental changes and only heat-shock genes altered expression of these gene groups. The data suggest that the maintenance of these gene expression patterns in a lineage represents epigenetically controlled robustness counteracting short-time adaptation processes. PMID:26231545

Defining the Molecular Character of the Developing and Adult Kidney Podocyte

PubMed Central

Brunskill, Eric W.; Georgas, Kylie; Rumballe, Bree; Little, Melissa H.; Potter, S. Steven

2011-01-01

Background The podocyte is a remarkable cell type, which encases the capillaries of the kidney glomerulus. Although mesodermal in origin it sends out axonal like projections that wrap around the capillaries. These extend yet finer projections, the foot processes, which interdigitate, leaving between them the slit diaphragms, through which the glomerular filtrate must pass. The podocytes are a subject of keen interest because of their key roles in kidney development and disease. Methodology/Principal Findings In this report we identified and characterized a novel transgenic mouse line, MafB-GFP, which specifically marked the kidney podocytes from a very early stage of development. These mice were then used to facilitate the fluorescent activated cell sorting based purification of podocytes from embryos at E13.5 and E15.5, as well as adults. Microarrays were then used to globally define the gene expression states of podocytes at these different developmental stages. A remarkable picture emerged, identifying the multiple sets of genes that establish the neuronal, muscle, and phagocytic properties of podocytes. The complete combinatorial code of transcription factors that create the podocyte was characterized, and the global lists of growth factors and receptors they express were defined. Conclusions/Significance The complete molecular character of the in vivo podocyte is established for the first time. The active molecular functions and biological processes further define their unique combination of features. The results provide a resource atlas of gene expression patterns of developing and adult podocytes that will help to guide further research of these incredible cells. PMID:21931791

Transcriptome responses to heat- and cold-stress in ladybirds (Cryptolaemus montrouzieri Mulasnt) analyzed by deep-sequencing.

PubMed

Zhang, Yuhong; Wu, Hongsheng; Xie, Jiaqin; Jiang, Ruixin; Deng, Congshuang; Pang, Hong

2015-11-19

Changed temperature not only threaten agricultural production, but they also affect individual biological behavior, population and community of many insects, and consequently reduce the stability of our ecosystem. Insect's ability to respond to temperature stress evolved through a complex adaptive process, thus resulting in varied temperature tolerance among different insects. Both high and low extreme temperatures are detrimental to insect development since they constitute an important abiotic stress capable of inducing abnormal biological responses. Many studies on heat or cold tolerance of ladybirds have focused on measurements of physiological and biochemical indexes such as supercooling point, higher/lower lethal temperatures, survival rate, dry body weight, water content, and developmental duration. And studies of the molecular mechanisms of ladybird responses to heat or cold stress have focused on single genes, such as those encoding heat shock proteins, but has not been analyzed by transcriptome profiling. In this study, we report the use of Digital Gene Expression (DGE) tag profiling to gain insight into transcriptional events associated with heat- and cold-stress in C. montrouzieri. About 6 million tags (49 bp in length) were sequenced in a heat stress group, a cold stress group and a negative control group. We obtained 687 and 573 genes that showed significantly altered expression levels following heat and cold shock treatments, respectively. Analysis of the global gene expression pattern suggested that 42 enzyme-encoding genes mapped to many Gene Ontology terms are associated with insect's response to heat- and cold-stress. These results provide a global assessment of genes and molecular mechanisms involved in heat and cold tolerance.

Global patterns of synchronization in human communications.

PubMed

Morales, Alfredo J; Vavilala, Vaibhav; Benito, Rosa M; Bar-Yam, Yaneer

2017-03-01

Social media are transforming global communication and coordination and provide unprecedented opportunities for studying socio-technical domains. Here we study global dynamical patterns of communication on Twitter across many scales. Underlying the observed patterns is both the diurnal rotation of the Earth, day and night, and the synchrony required for contingency of actions between individuals. We find that urban areas show a cyclic contraction and expansion that resembles heartbeats linked to social rather than natural cycles. Different urban areas have characteristic signatures of daily collective activities. We show that the differences detected are consistent with a new emergent global synchrony that couples behaviour in distant regions across the world. Although local synchrony is the major force that shapes the collective behaviour in cities, a larger-scale synchronization is beginning to occur. © 2017 The Author(s).

Separation of the global and local components in functional near-infrared spectroscopy signals using principal component spatial filtering

PubMed Central

Zhang, Xian; Noah, Jack Adam; Hirsch, Joy

2016-01-01

Abstract. Global systemic effects not specific to a task can be prominent in functional near-infrared spectroscopy (fNIRS) signals and the separation of task-specific fNIRS signals and global nonspecific effects is challenging due to waveform correlations. We describe a principal component spatial filter algorithm for separation of the global and local effects. The effectiveness of the approach is demonstrated using fNIRS signals acquired during a right finger-thumb tapping task where the response patterns are well established. Both the temporal waveforms and the spatial pattern consistencies between oxyhemoglobin and deoxyhemoglobin signals are significantly improved, consistent with the basic physiological basis of fNIRS signals and the expected pattern of activity associated with the task. PMID:26866047

Global patterns of synchronization in human communications

PubMed Central

Vavilala, Vaibhav; Benito, Rosa M.; Bar-Yam, Yaneer

2017-01-01

Social media are transforming global communication and coordination and provide unprecedented opportunities for studying socio-technical domains. Here we study global dynamical patterns of communication on Twitter across many scales. Underlying the observed patterns is both the diurnal rotation of the Earth, day and night, and the synchrony required for contingency of actions between individuals. We find that urban areas show a cyclic contraction and expansion that resembles heartbeats linked to social rather than natural cycles. Different urban areas have characteristic signatures of daily collective activities. We show that the differences detected are consistent with a new emergent global synchrony that couples behaviour in distant regions across the world. Although local synchrony is the major force that shapes the collective behaviour in cities, a larger-scale synchronization is beginning to occur. PMID:28250100

Macrogenomic engineering via modulation of the scaling of chromatin packing density.

PubMed

Almassalha, Luay M; Bauer, Greta M; Wu, Wenli; Cherkezyan, Lusik; Zhang, Di; Kendra, Alexis; Gladstein, Scott; Chandler, John E; VanDerway, David; Seagle, Brandon-Luke L; Ugolkov, Andrey; Billadeau, Daniel D; O'Halloran, Thomas V; Mazar, Andrew P; Roy, Hemant K; Szleifer, Igal; Shahabi, Shohreh; Backman, Vadim

2017-11-01

Many human diseases result from the dysregulation of the complex interactions between tens to thousands of genes. However, approaches for the transcriptional modulation of many genes simultaneously in a predictive manner are lacking. Here, through the combination of simulations, systems modelling and in vitro experiments, we provide a physical regulatory framework based on chromatin packing-density heterogeneity for modulating the genomic information space. Because transcriptional interactions are essentially chemical reactions, they depend largely on the local physical nanoenvironment. We show that the regulation of the chromatin nanoenvironment allows for the predictable modulation of global patterns in gene expression. In particular, we show that the rational modulation of chromatin density fluctuations can lead to a decrease in global transcriptional activity and intercellular transcriptional heterogeneity in cancer cells during chemotherapeutic responses to achieve near-complete cancer cell killing in vitro. Our findings represent a 'macrogenomic engineering' approach to modulating the physical structure of chromatin for whole-scale transcriptional modulation.

Effects of seawater acidification on gene expression: resolving broader-scale trends in sea urchins.

PubMed

Evans, Tyler G; Watson-Wynn, Priscilla

2014-06-01

Sea urchins are ecologically and economically important calcifying organisms threatened by acidification of the global ocean caused by anthropogenic CO2 emissions. Propelled by the sequencing of the purple sea urchin (Strongylocentrotus purpuratus) genome, profiling changes in gene expression during exposure to high pCO2 seawater has emerged as a powerful and increasingly common method to infer the response of urchins to ocean change. However, analyses of gene expression are sensitive to experimental methodology, and comparisons between studies of genes regulated by ocean acidification are most often made in the context of major caveats. Here we perform meta-analyses as a means of minimizing experimental discrepancies and resolving broader-scale trends regarding the effects of ocean acidification on gene expression in urchins. Analyses across eight studies and four urchin species largely support prevailing hypotheses about the impact of ocean acidification on marine calcifiers. The predominant expression pattern involved the down-regulation of genes within energy-producing pathways, a clear indication of metabolic depression. Genes with functions in ion transport were significantly over-represented and are most plausibly contributing to intracellular pH regulation. Expression profiles provided extensive evidence for an impact on biomineralization, epitomized by the down-regulation of seven spicule matrix proteins. In contrast, expression profiles provided limited evidence for CO2-mediated developmental delay or induction of a cellular stress response. Congruence between studies of gene expression and the ocean acidification literature in general validates the accuracy of gene expression in predicting the consequences of ocean change and justifies its continued use in future studies. © 2014 Marine Biological Laboratory.

Global Three-Dimensional Atmospheric Structure of the Atlantic Multidecadal Oscillation as Revealed by Two Reanalyses

NASA Astrophysics Data System (ADS)

Stuckman, Scott Seele

This study is a first documentation of the structure of the entire AMO life cycle, including extreme and transition phases, throughout the global troposphere. The extreme phase climate signature is constructed based on the strongest and most robust patterns identified by two methods (linear correlation and composite analyses), two reanalysis datasets (the National Centers for Environmental Prediction/National Center for Atmospheric Research and Twentieth Century Reanalysis, supplemented with precipitation data from the University of Delaware dataset) and data from two consecutive AMO cycles. The first characterization of the AMO transition phases uses a transition index based on the time derivative of AMO index. When trying to compare the zonal mean structure of AMO with the El Niño-Southern Oscillation (ENSO), a literature search showed the zonal mean structure of ENSO remained unpublished, despite the otherwise generally well-characterized horizontal structures. Therefore this study includes a seasonal analysis of the ENSO zonal mean structure during boreal winter (DJF) and summer (JJA). The AMO extreme phase is characterized by a blend of low and middle latitude centers of action, with the associated tilt of geopotential height anomaly patterns consistent with off-equatorial heating patterns generated by the Held idealized model. The surface climate signature is connected to the upper air with baroclinic vertical structure over the North Atlantic but barotropic structures elsewhere. The associated zonal mean circulation features three circulation cells globally with strong inter-hemispheric mixing that suggests the traditional view of the AMO involving a Northern-Southern Hemisphere asymmetry is accurate only near the surface. The AMO transition phase features a more equatorial-based climate signature and associated geopotential height anomaly patterns consistent with the Matsuno-Gill idealized model. The zonal mean circulation of the transition phases features six, rather than three, circulation cells globally. The only baroclinic structure, over North America, and several barotropic structures are positioned west of corresponding similar structures during the AMO extreme phase, suggesting an eastward evolution of climate anomalies as the AMO progresses from a cool-to-warm transition phase to warm phase. The Pacific-based climate signature resembles the IPO warm phase and it is proposed the AMO and IPO are different basin-wide expressions of a single multidecadal oscillation. The identification of an AMO transition phase climate signature distinct from the extreme phase suggests transition phases are not neutral and may provide an additional source of information for characterizing climate cycles.

Glucocorticoids Affect 24 h Clock Genes Expression in Human Adipose Tissue Explant Cultures

PubMed Central

Gómez-Abellán, Purificación; Díez-Noguera, Antoni; Madrid, Juan A.; Luján, Juan A.; Ordovás, José M.; Garaulet, Marta

2012-01-01

Aims to examine firstly whether CLOCK exhibits a circadian expression in human visceral (V) and subcutaneous (S) adipose tissue (AT) in vitro as compared with BMAL1 and PER2, and secondly to investigate the possible effect of the glucocorticoid analogue dexamethasone (DEX) on positive and negative clock genes expression. Subjects and Methods VAT and SAT biopsies were obtained from morbid obese women (body mass index≥40 kg/m2) (n = 6). In order to investigate rhythmic expression pattern of clock genes and the effect of DEX on CLOCK, PER2 and BMAL1 expression, control AT (without DEX) and AT explants treated with DEX (2 hours) were cultured during 24 h and gene expression was analyzed at the following times: 10:00 h, 14:00 h, 18:00 h, 22:00 h, 02:00 h and 06:00 h, using qRT-PCR. Results CLOCK, BMAL1 and PER2 expression exhibited circadian patterns in both VAT and SAT explants that were adjusted to a typical 24 h sinusoidal curve. PER2 expression (negative element) was in antiphase with respect to CLOCK and in phase with BMAL1 expression (both positive elements) in the SAT (situation not present in VAT). A marked effect of DEX exposure on both positive and negative clock genes expression patterns was observed. Indeed, DEX treatment modified the rhythmicity pattern towards altered patterns with a period lower than 24 hours in all genes and in both tissues. Conclusions 24 h patterns in CLOCK and BMAL1 (positive clock elements) and PER2 (negative element) mRNA levels were observed in human adipose explants. These patterns were altered by dexamethasone exposure. PMID:23251369

Expression profiling of the mouse early embryo: Reflections and Perspectives

PubMed Central

Ko, Minoru S. H.

2008-01-01

Laboratory mouse plays important role in our understanding of early mammalian development and provides invaluable model for human early embryos, which are difficult to study for ethical and technical reasons. Comprehensive collection of cDNA clones, their sequences, and complete genome sequence information, which have been accumulated over last two decades, have provided even more advantages to mouse models. Here the progress in global gene expression profiling in early mouse embryos and, to some extent, stem cells are reviewed and the future directions and challenges are discussed. The discussions include the restatement of global gene expression profiles as snapshot of cellular status, and subsequent distinction between the differentiation state and physiological state of the cells. The discussions then extend to the biological problems that can be addressed only through global expression profiling, which include: bird’s-eye view of global gene expression changes, molecular index for developmental potency, cell lineage trajectory, microarray-guided cell manipulation, and the possibility of delineating gene regulatory cascades and networks. PMID:16739220

mRNA-Seq Analysis of the Pseudoperonospora cubensis Transcriptome During Cucumber (Cucumis sativus L.) Infection

PubMed Central

Hamilton, John P.; Vaillancourt, Brieanne; Buell, C. Robin; Day, Brad

2012-01-01

Pseudoperonospora cubensis, an oomycete, is the causal agent of cucurbit downy mildew, and is responsible for significant losses on cucurbit crops worldwide. While other oomycete plant pathogens have been extensively studied at the molecular level, Ps. cubensis and the molecular basis of its interaction with cucurbit hosts has not been well examined. Here, we present the first large-scale global gene expression analysis of Ps. cubensis infection of a susceptible Cucumis sativus cultivar, ‘Vlaspik’, and identification of genes with putative roles in infection, growth, and pathogenicity. Using high throughput whole transcriptome sequencing, we captured differential expression of 2383 Ps. cubensis genes in sporangia and at 1, 2, 3, 4, 6, and 8 days post-inoculation (dpi). Additionally, comparison of Ps. cubensis expression profiles with expression profiles from an infection time course of the oomycete pathogen Phytophthora infestans on Solanum tuberosum revealed similarities in expression patterns of 1,576–6,806 orthologous genes suggesting a substantial degree of overlap in molecular events in virulence between the biotrophic Ps. cubensis and the hemi-biotrophic P. infestans. Co-expression analyses identified distinct modules of Ps. cubensis genes that were representative of early, intermediate, and late infection stages. Collectively, these expression data have advanced our understanding of key molecular and genetic events in the virulence of Ps. cubensis and thus, provides a foundation for identifying mechanism(s) by which to engineer or effect resistance in the host. PMID:22545137

Spatial Pattern of Standing Timber Value across the Brazilian Amazon

PubMed Central

Ahmed, Sadia E.; Ewers, Robert M.

2012-01-01

The Amazon is a globally important system, providing a host of ecosystem services from climate regulation to food sources. It is also home to a quarter of all global diversity. Large swathes of forest are removed each year, and many models have attempted to predict the spatial patterns of this forest loss. The spatial patterns of deforestation are determined largely by the patterns of roads that open access to frontier areas and expansion of the road network in the Amazon is largely determined by profit seeking logging activities. Here we present predictions for the spatial distribution of standing value of timber across the Amazon. We show that the patterns of timber value reflect large-scale ecological gradients, determining the spatial distribution of functional traits of trees which are, in turn, correlated with timber values. We expect that understanding the spatial patterns of timber value across the Amazon will aid predictions of logging movements and thus predictions of potential future road developments. These predictions in turn will be of great use in estimating the spatial patterns of deforestation in this globally important biome. PMID:22590520

Geo-located Twitter as proxy for global mobility patterns.

PubMed

Hawelka, Bartosz; Sitko, Izabela; Beinat, Euro; Sobolevsky, Stanislav; Kazakopoulos, Pavlos; Ratti, Carlo

2014-05-27

Pervasive presence of location-sharing services made it possible for researchers to gain an unprecedented access to the direct records of human activity in space and time. This article analyses geo-located Twitter messages in order to uncover global patterns of human mobility. Based on a dataset of almost a billion tweets recorded in 2012, we estimate the volume of international travelers by country of residence. Mobility profiles of different nations were examined based on such characteristics as mobility rate, radius of gyration, diversity of destinations, and inflow-outflow balance. Temporal patterns disclose the universally valid seasons of increased international mobility and the particular character of international travels of different nations. Our analysis of the community structure of the Twitter mobility network reveals spatially cohesive regions that follow the regional division of the world. We validate our result using global tourism statistics and mobility models provided by other authors and argue that Twitter is exceptionally useful for understanding and quantifying global mobility patterns.

A global assessment of market accessibility and market influence for global environmental change studies

NASA Astrophysics Data System (ADS)

Verburg, Peter H.; Ellis, Erle C.; Letourneau, Aurelien

2011-07-01

Markets influence the global patterns of urbanization, deforestation, agriculture and other land use systems. Yet market influence is rarely incorporated into spatially explicit global studies of environmental change, largely because consistent global data are lacking below the national level. Here we present the first high spatial resolution gridded data depicting market influence globally. The data jointly represent variations in both market strength and accessibility based on three market influence indices derived from an index of accessibility to market locations and national level gross domestic product (purchasing power parity). These indices show strong correspondence with human population density while also revealing several distinct and useful relationships with other global environmental patterns. As market influence grows, the need for high resolution global data on market influence and its dynamics will become increasingly important to understanding and forecasting global environmental change.

Global preamplification simplifies targeted mRNA quantification

PubMed Central

Kroneis, Thomas; Jonasson, Emma; Andersson, Daniel; Dolatabadi, Soheila; Ståhlberg, Anders

2017-01-01

The need to perform gene expression profiling using next generation sequencing and quantitative real-time PCR (qPCR) on small sample sizes and single cells is rapidly expanding. However, to analyse few molecules, preamplification is required. Here, we studied global and target-specific preamplification using 96 optimised qPCR assays. To evaluate the preamplification strategies, we monitored the reactions in real-time using SYBR Green I detection chemistry followed by melting curve analysis. Next, we compared yield and reproducibility of global preamplification to that of target-specific preamplification by qPCR using the same amount of total RNA. Global preamplification generated 9.3-fold lower yield and 1.6-fold lower reproducibility than target-specific preamplification. However, the performance of global preamplification is sufficient for most downstream applications and offers several advantages over target-specific preamplification. To demonstrate the potential of global preamplification we analysed the expression of 15 genes in 60 single cells. In conclusion, we show that global preamplification simplifies targeted gene expression profiling of small sample sizes by a flexible workflow. We outline the pros and cons for global preamplification compared to target-specific preamplification. PMID:28332609

Fox (forkhead) genes are involved in the dorso-ventral patterning of the Xenopus mesoderm.

PubMed

El-Hodiri, H; Bhatia-Dey, N; Kenyon, K; Ault, K; Dirksen, M; Jamrich, M

2001-01-01

Fox (forkhead/winged helix) genes encode a family of transcription factors that are involved in embryonic pattern formation, regulation of tissue specific gene expression and tumorigenesis. Several of them are transcribed during Xenopus embryogenesis and are important for the patterning of ectoderm, mesoderm and endoderm. We have isolated three forkhead genes that are activated during gastrulation and play an important role in the dorso-ventral patterning of the mesoderm. XFKH1 (FoxA4b), the first vertebrate forkhead gene to be implicated in embryonic pattern formation, is expressed in the Spemann-Mangold organizer region and later in the embryonic notochord. XFKH7, the Xenopus orthologue of the murine Mfh1(Foxc2), is expressed in the presomitic mesoderm, but not in the notochord or lateral plate mesoderm. Finally, XFD-13'(FoxF1b)1 is expressed in the lateral plate mesoderm, but not in the notochord or presomitic mesoderm. Expression pattern and functional experiments indicate that these three forkhead genes are involved in the dorso-ventral patterning of the mesoderm.

Identification of genes differentially expressed during interaction of resistant and susceptible apple cultivars (Malus × domestica) with Erwinia amylovora

PubMed Central

2010-01-01

Background The necrogenic enterobacterium, Erwinia amylovora is the causal agent of the fire blight (FB) disease in many Rosaceaespecies, including apple and pear. During the infection process, the bacteria induce an oxidative stress response with kinetics similar to those induced in an incompatible bacteria-plant interaction. No resistance mechanism to E. amylovora in host plants has yet been characterized, recent work has identified some molecular events which occur in resistant and/or susceptible host interaction with E. amylovora: In order to understand the mechanisms that characterize responses to FB, differentially expressed genes were identified by cDNA-AFLP analysis in resistant and susceptible apple genotypes after inoculation with E. amylovora. Results cDNA were isolated from M.26 (susceptible) and G.41 (resistant) apple tissues collected 2 h and 48 h after challenge with a virulent E. amylovora strain or mock (buffer) inoculated. To identify differentially expressed transcripts, electrophoretic banding patterns were obtained from cDNAs. In the AFLP experiments, M.26 and G.41 showed different patterns of expression, including genes specifically induced, not induced, or repressed by E. amylovora. In total, 190 ESTs differentially expressed between M.26 and G.41 were identified using 42 pairs of AFLP primers. cDNA-AFLP analysis of global EST expression in a resistant and a susceptible apple genotype identified different major classes of genes. EST sequencing data showed that genes linked to resistance, encoding proteins involved in recognition, signaling, defense and apoptosis, were modulated by E. amylovora in its host plant. The expression time course of some of these ESTs selected via a bioinformatic analysis has been characterized. Conclusion These data are being used to develop hypotheses of resistance or susceptibility mechanisms in Malus to E. amylovora and provide an initial categorization of genes possibly involved in recognition events, early signaling responses the subsequent development of resistance or susceptibility. These data also provided potential candidates for improving apple resistance to fire blight either by marker-assisted selection or genetic engineering. PMID:20047654

Insights into the diurnal cycle of global Earth outgoing radiation using a numerical weather prediction model

NASA Astrophysics Data System (ADS)

Gristey, Jake J.; Chiu, J. Christine; Gurney, Robert J.; Morcrette, Cyril J.; Hill, Peter G.; Russell, Jacqueline E.; Brindley, Helen E.

2018-04-01

A globally complete, high temporal resolution and multiple-variable approach is employed to analyse the diurnal cycle of Earth's outgoing energy flows. This is made possible via the use of Met Office model output for September 2010 that is assessed alongside regional satellite observations throughout. Principal component analysis applied to the long-wave component of modelled outgoing radiation reveals dominant diurnal patterns related to land surface heating and convective cloud development, respectively explaining 68.5 and 16.0 % of the variance at the global scale. The total variance explained by these first two patterns is markedly less than previous regional estimates from observations, and this analysis suggests that around half of the difference relates to the lack of global coverage in the observations. The first pattern is strongly and simultaneously coupled to the land surface temperature diurnal variations. The second pattern is strongly coupled to the cloud water content and height diurnal variations, but lags the cloud variations by several hours. We suggest that the mechanism controlling the delay is a moistening of the upper troposphere due to the evaporation of anvil cloud. The short-wave component of modelled outgoing radiation, analysed in terms of albedo, exhibits a very dominant pattern explaining 88.4 % of the variance that is related to the angle of incoming solar radiation, and a second pattern explaining 6.7 % of the variance that is related to compensating effects from convective cloud development and marine stratocumulus cloud dissipation. Similar patterns are found in regional satellite observations, but with slightly different timings due to known model biases. The first pattern is controlled by changes in surface and cloud albedo, and Rayleigh and aerosol scattering. The second pattern is strongly coupled to the diurnal variations in both cloud water content and height in convective regions but only cloud water content in marine stratocumulus regions, with substantially shorter lag times compared with the long-wave counterpart. This indicates that the short-wave radiation response to diurnal cloud development and dissipation is more rapid, which is found to be robust in the regional satellite observations. These global, diurnal radiation patterns and their coupling with other geophysical variables demonstrate the process-level understanding that can be gained using this approach and highlight a need for global, diurnal observing systems for Earth outgoing radiation in the future.

Clustering change patterns using Fourier transformation with time-course gene expression data.

PubMed

Kim, Jaehee

2011-01-01

To understand the behavior of genes, it is important to explore how the patterns of gene expression change over a period of time because biologically related gene groups can share the same change patterns. In this study, the problem of finding similar change patterns is induced to clustering with the derivative Fourier coefficients. This work is aimed at discovering gene groups with similar change patterns which share similar biological properties. We developed a statistical model using derivative Fourier coefficients to identify similar change patterns of gene expression. We used a model-based method to cluster the Fourier series estimation of derivatives. We applied our model to cluster change patterns of yeast cell cycle microarray expression data with alpha-factor synchronization. It showed that, as the method clusters with the probability-neighboring data, the model-based clustering with our proposed model yielded biologically interpretable results. We expect that our proposed Fourier analysis with suitably chosen smoothing parameters could serve as a useful tool in classifying genes and interpreting possible biological change patterns.

BnDGAT1s Function Similarly in Oil Deposition and Are Expressed with Uniform Patterns in Tissues of Brassica napus.

PubMed

Zhao, Cuizhu; Li, Huan; Zhang, Wenxue; Wang, Hailan; Xu, Aixia; Tian, Jianhua; Zou, Jitao; Taylor, David C; Zhang, Meng

2017-01-01

As an allotetraploid oilcrop, Brassica napus contains four duplicated Acyl-CoA:diacylglycerol acyltransferase 1 ( DGAT1 ) genes, which catalyze one of the rate-limiting steps in triacylglycerol (TAG) biosynthesis in plants. While all four BnDGAT1 s have been expressed functionally in yeast, their expression patterns in different germplasms and tissues and also consequent contribution to seed oil accumulation in planta remain to be elucidated. In this study, the coding regions of the four BnDGAT1s were expressed in an Arabidopsis dgat1 mutant. All four BnDGAT1s showed similar effects on oil content and fatty acid composition, a result which is different from that observed in previous studies of their expression in yeast. Expression patterns of BnDGAT1s were analyzed in developing seeds of 34 B. napus inbred lines and in different tissues of 14 lines. Different expression patterns were observed for the four BnDGAT1 s, which suggests that they express independently or randomly in different germplasm sources. Higher expression of BnDGAT1s was correlated with higher seed oil content lines. Tissue-specific analyses showed that the BnDGAT1 s were expressed in a uniform pattern in different tissues. Our results suggest that it is important to maintain expression of the four BnDGAT1s for maximum return on oil content.

Aging and Gene Expression in the Primate Brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.

2005-02-18

It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes inmore » the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.« less

Plain faces are more expressive: comparative study of facial colour, mobility and musculature in primates

PubMed Central

Santana, Sharlene E.; Dobson, Seth D.; Diogo, Rui

2014-01-01

Facial colour patterns and facial expressions are among the most important phenotypic traits that primates use during social interactions. While colour patterns provide information about the sender's identity, expressions can communicate its behavioural intentions. Extrinsic factors, including social group size, have shaped the evolution of facial coloration and mobility, but intrinsic relationships and trade-offs likely operate in their evolution as well. We hypothesize that complex facial colour patterning could reduce how salient facial expressions appear to a receiver, and thus species with highly expressive faces would have evolved uniformly coloured faces. We test this hypothesis through a phylogenetic comparative study, and explore the underlying morphological factors of facial mobility. Supporting our hypothesis, we find that species with highly expressive faces have plain facial colour patterns. The number of facial muscles does not predict facial mobility; instead, species that are larger and have a larger facial nucleus have more expressive faces. This highlights a potential trade-off between facial mobility and colour patterning in primates and reveals complex relationships between facial features during primate evolution. PMID:24850898

Characterization of basal gene expression trends over a diurnal cycle in Xiphophorus maculatus skin, brain and liver.

PubMed

Lu, Yuan; Reyes, Jose; Walter, Sean; Gonzalez, Trevor; Medrano, Geraldo; Boswell, Mikki; Boswell, William; Savage, Markita; Walter, Ronald

2018-06-01

Evolutionarily conserved diurnal circadian mechanisms maintain oscillating patterns of gene expression based on the day-night cycle. Xiphophorus fish have been used to evaluate transcriptional responses after exposure to various light sources and it was determined that each source incites distinct genetic responses in skin tissue. However, basal expression levels of genes that show oscillating expression patterns in day-night cycle, may affect the outcomes of such experiments, since basal gene expression levels at each point in the circadian path may influence the profile of identified light responsive genes. Lack of knowledge regarding diurnal fluctuations in basal gene expression patterns may confound the understanding of genetic responses to external stimuli (e.g., light) since the dynamic nature of gene expression implies animals subjected to stimuli at different times may be at very different stages within the continuum of genetic homeostasis. We assessed basal gene expression changes over a 24-hour period in 200 select Xiphophorus gene targets known to transcriptionally respond to various types of light exposure. We identified 22 genes in skin, 36 genes in brain and 28 genes in liver that exhibit basal oscillation of expression patterns. These genes, including known circadian regulators, produced the expected expression patterns over a 24-hour cycle when compared to circadian regulatory genes identified in other species, especially human and other vertebrate animal models. Our results suggest the regulatory network governing diurnal oscillating gene expression is similar between Xiphophorus and other vertebrates for the three Xiphophorus organs tested. In addition, we were able to categorize light responsive gene sets in Xiphophorus that do, and do not, exhibit circadian based oscillating expression patterns. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative epigenetic influence of autologous versus fetal bovine serum on mesenchymal stem cells through in vitro osteogenic and adipogenic differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fani, Nesa; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran

Mesenchymal stem cells (MSCs) derived from bone marrow (BM) represents a useful source of adult stem cells for cell therapy and tissue engineering. MSCs are present at a low frequency in the BM; therefore expansion is necessary before performing clinical studies. Fetal bovine serum (FBS) as a nutritional supplement for in vitro culture of MSCs is a suitable additive for human cell culture, but not regarding subsequent use of these cells for clinical treatment of human patients due to the risk of viral and prion transmission as well as xenogeneic immune responses after transplantation. Recently, autologous serum (AS) has beenmore » as a supplement to replace FBS in culture medium. We compared the effect of FBS versus AS on the histone modification pattern of MSCs through in vitro osteogenesis and adipogenesis. Differentiation of stem cells under various serum conditions to a committed state involves global changes in epigenetic patterns that are critically determined by chromatin modifications. Chromatin immunoprecipitation (ChIP) coupled with real-time PCR showed significant changes in the acetylation and methylation patterns in lysine 9 (Lys9) of histone H3 on the regulatory regions of stemness (Nanog, Sox2, Rex1), osteogenic (Runx2, Oc, Sp7) and adipogenic (Ppar-γ, Lpl, adiponectin) marker genes in undifferentiated MSCs, FBS and AS. All epigenetic changes occurred in a serum dependent manner which resulted in higher expression level of stemness genes in undifferentiated MSCs compared to differentiated MSCs and increased expression levels of osteogenic genes in AS compared to FBS. Adipogenic genes showed greater expression in FBS compared to AS. These findings have demonstrated the epigenetic influence of serum culture conditions on differentiation potential of MSCs, which suggest that AS is possibly more efficient serum for osteogenic differentiation of MSCs in cell therapy purposes. - Highlights: • Bone marrow derived MSC could proliferate in AS as well as in FBS. • Different serum conditions influence epigentic patterns of genes. • Osteogenic genes specifically up-regulate in AS in response to differentiation signals.« less

Haloperidol induces pharmacoepigenetic response by modulating miRNA expression, global DNA methylation and expression profiles of methylation maintenance genes and genes involved in neurotransmission in neuronal cells.

PubMed

Swathy, Babu; Banerjee, Moinak

2017-01-01

Haloperidol has been extensively used in various psychiatric conditions. It has also been reported to induce severe side effects. We aimed to evaluate whether haloperidol can influence host methylome, and if so what are the possible mechanisms for it in neuronal cells. Impact on host methylome and miRNAs can have wide spread alterations in gene expression, which might possibly help in understanding how haloperidol may impact treatment response or induce side effects. SK-N-SH, a neuroblasoma cell line was treated with haloperidol at 10μm concentration for 24 hours and global DNA methylation was evaluated. Methylation at global level is maintained by methylation maintenance machinery and certain miRNAs. Therefore, the expression of methylation maintenance genes and their putative miRNA expression profiles were assessed. These global methylation alterations could result in gene expression changes. Therefore genes expressions for neurotransmitter receptors, regulators, ion channels and transporters were determined. Subsequently, we were also keen to identify a strong candidate miRNA based on biological and in-silico approach which can reflect on the pharmacoepigenetic trait of haloperidol and can also target the altered neuroscience panel of genes used in the study. Haloperidol induced increase in global DNA methylation which was found to be associated with corresponding increase in expression of various epigenetic modifiers that include DNMT1, DNMT3A, DNMT3B and MBD2. The expression of miR-29b that is known to putatively regulate the global methylation by modulating the expression of epigenetic modifiers was observed to be down regulated by haloperidol. In addition to miR-29b, miR-22 was also found to be downregulated by haloperidol treatment. Both these miRNA are known to putatively target several genes associated with various epigenetic modifiers, pharmacogenes and neurotransmission. Interestingly some of these putative target genes involved in neurotransmission were observed to be upregulated while CHRM2 gene expression was down regulated. Haloperidol can influence methylation traits thereby inducing a pharmacoepigenomic response, which seems to be regulated by DNMTs and their putative miRNA expression. Increased methylation seems to influence CHRM2 gene expression while microRNA could influence neurotransmission, pharmacogene expression and methylation events. Altered expression of various therapeutically relevant genes and miRNA expression, could account for their role in therapeutic response or side effects.

Haloperidol induces pharmacoepigenetic response by modulating miRNA expression, global DNA methylation and expression profiles of methylation maintenance genes and genes involved in neurotransmission in neuronal cells

PubMed Central

Swathy, Babu

2017-01-01

Introduction Haloperidol has been extensively used in various psychiatric conditions. It has also been reported to induce severe side effects. We aimed to evaluate whether haloperidol can influence host methylome, and if so what are the possible mechanisms for it in neuronal cells. Impact on host methylome and miRNAs can have wide spread alterations in gene expression, which might possibly help in understanding how haloperidol may impact treatment response or induce side effects. Methods SK-N-SH, a neuroblasoma cell line was treated with haloperidol at 10μm concentration for 24 hours and global DNA methylation was evaluated. Methylation at global level is maintained by methylation maintenance machinery and certain miRNAs. Therefore, the expression of methylation maintenance genes and their putative miRNA expression profiles were assessed. These global methylation alterations could result in gene expression changes. Therefore genes expressions for neurotransmitter receptors, regulators, ion channels and transporters were determined. Subsequently, we were also keen to identify a strong candidate miRNA based on biological and in-silico approach which can reflect on the pharmacoepigenetic trait of haloperidol and can also target the altered neuroscience panel of genes used in the study. Results Haloperidol induced increase in global DNA methylation which was found to be associated with corresponding increase in expression of various epigenetic modifiers that include DNMT1, DNMT3A, DNMT3B and MBD2. The expression of miR-29b that is known to putatively regulate the global methylation by modulating the expression of epigenetic modifiers was observed to be down regulated by haloperidol. In addition to miR-29b, miR-22 was also found to be downregulated by haloperidol treatment. Both these miRNA are known to putatively target several genes associated with various epigenetic modifiers, pharmacogenes and neurotransmission. Interestingly some of these putative target genes involved in neurotransmission were observed to be upregulated while CHRM2 gene expression was down regulated. Conclusions Haloperidol can influence methylation traits thereby inducing a pharmacoepigenomic response, which seems to be regulated by DNMTs and their putative miRNA expression. Increased methylation seems to influence CHRM2 gene expression while microRNA could influence neurotransmission, pharmacogene expression and methylation events. Altered expression of various therapeutically relevant genes and miRNA expression, could account for their role in therapeutic response or side effects. PMID:28886082

Climate implications of including albedo effects in terrestrial carbon policy

NASA Astrophysics Data System (ADS)

Jones, A. D.; Collins, W.; Torn, M. S.; Calvin, K. V.

2012-12-01

Proposed strategies for managing terrestrial carbon in order to mitigate anthropogenic climate change, such as financial incentives for afforestation, soil carbon sequestration, or biofuel production, largely ignore the direct effects of land use change on climate via biophysical processes that alter surface energy and water budgets. Subsequent influences on temperature, hydrology, and atmospheric circulation at regional and global scales could potentially help or hinder climate stabilization efforts. Because these policies often rely on payments or credits expressed in units of CO2-equivalents, accounting for biophysical effects would require a metric for comparing the strength of biophysical climate perturbation from land use change to that of emitting CO2. One such candidate metric that has been suggested in the literature on land use impacts is radiative forcing, which underlies the global warming potential metric used to compare the climate effects of various greenhouse gases with one another. Expressing land use change in units of radiative forcing is possible because albedo change results in a net top-of-atmosphere radiative flux change. However, this approach has also been critiqued on theoretical grounds because not all climatic changes associated with land use change are principally radiative in nature, e.g. changes in hydrology or the vertical distribution of heat within the atmosphere, and because the spatial scale of land use change forcing differs from that of well-mixed greenhouse gases. To explore the potential magnitude of this discrepancy in the context of plausible scenarios of future land use change, we conduct three simulations with the Community Climate System Model 4 (CCSM4) utilizing a slab ocean model. Each simulation examines the effect of a stepwise change in forcing relative to a pre-industrial control simulation: 1) widespread conversion of forest land to crops resulting in approximately 1 W/m2 global-mean radiative forcing from albedo change, 2) an increase in CO2 concentrations that exactly balances the forcing from land use change at the global level, and 3) a simulation combining the first two effects, resulting in net zero global-mean forcing as would occur in an idealized carbon cap-and-trade scheme that accounts for the albedo effect of land use change. The pattern of land use change that we examine is derived from an integrated assessment model that accounts for population, demographic, technological, and policy changes over the 21st century. We find significant differences in the pattern of climate change associated with each of these forcing scenarios, demonstrating the non-additivity of radiative forcing from land-use change and greenhouse gases in the context of a hypothetical scenario of future land use change. These results have implications for the development of land use and climate policies.

Regional expression patterns of taste receptors and gustducin in the mouse tongue.

PubMed

Kim, Mi-Ryung; Kusakabe, Yuko; Miura, Hirohito; Shindo, Yoichiro; Ninomiya, Yuzo; Hino, Akihiro

2003-12-12

In order to understand differences in taste sensitivities of taste bud cells between the anterior and posterior part of tongue, it is important to analyze the regional expression patterns of genes related to taste signal transduction on the tongue. Here we examined the expression pattern of a taste receptor family, the T1r family, and gustducin in circumvallate and fungiform papillae of the mouse tongue using double-labeled in situ hybridization. Each member of the T1r family was expressed in both circumvallate and fungiform papillae with some differences in their expression patterns. The most striking difference between fungiform and circumvallate papillae was observed in their co-expression patterns of T1r2, T1r3, and gustducin. T1r2-positive cells in fungiform papillae co-expressed T1r3 and gustducin, whereas T1r2 and T1r3 double-positive cells in circumvallate papillae merely expressed gustducin. These results suggested that in fungiform papillae, gustducin might play a role in the sweet taste signal transduction cascade mediated by a sweet receptor based on the T1r2 and T1r3 combination, in fungiform papillae.

Identification of Human HK Genes and Gene Expression Regulation Study in Cancer from Transcriptomics Data Analysis

PubMed Central

Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun

2013-01-01

The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer. PMID:23382867

Integrated Analyses of microRNAs Demonstrate Their Widespread Influence on Gene Expression in High-Grade Serous Ovarian Carcinoma

PubMed Central

Levine, Douglas A.; Mankoo, Parminder; Schultz, Nikolaus; Du, Ying; Zhang, Yiqun; Larsson, Erik; Sheridan, Robert; Xiao, Weimin; Spellman, Paul T.; Getz, Gad; Wheeler, David A.; Perou, Charles M.; Gibbs, Richard A.; Sander, Chris; Hayes, D. Neil; Gunaratne, Preethi H.

2012-01-01

Background The Cancer Genome Atlas (TCGA) Network recently comprehensively catalogued the molecular aberrations in 487 high-grade serous ovarian cancers, with much remaining to be elucidated regarding the microRNAs (miRNAs). Here, using TCGA ovarian data, we surveyed the miRNAs, in the context of their predicted gene targets. Methods and Results Integration of miRNA and gene patterns yielded evidence that proximal pairs of miRNAs are processed from polycistronic primary transcripts, and that intronic miRNAs and their host gene mRNAs derive from common transcripts. Patterns of miRNA expression revealed multiple tumor subtypes and a set of 34 miRNAs predictive of overall patient survival. In a global analysis, miRNA:mRNA pairs anti-correlated in expression across tumors showed a higher frequency of in silico predicted target sites in the mRNA 3′-untranslated region (with less frequency observed for coding sequence and 5′-untranslated regions). The miR-29 family and predicted target genes were among the most strongly anti-correlated miRNA:mRNA pairs; over-expression of miR-29a in vitro repressed several anti-correlated genes (including DNMT3A and DNMT3B) and substantially decreased ovarian cancer cell viability. Conclusions This study establishes miRNAs as having a widespread impact on gene expression programs in ovarian cancer, further strengthening our understanding of miRNA biology as it applies to human cancer. As with gene transcripts, miRNAs exhibit high diversity reflecting the genomic heterogeneity within a clinically homogeneous disease population. Putative miRNA:mRNA interactions, as identified using integrative analysis, can be validated. TCGA data are a valuable resource for the identification of novel tumor suppressive miRNAs in ovarian as well as other cancers. PMID:22479643

Characterization of Transcriptional Complexity during Adipose Tissue Development in Bovines of Different Ages and Sexes

PubMed Central

Zhou, Yang; Sun, Jiajie; Li, Congjun; Wang, Yanhong; Li, Lan; Cai, Hanfang; Lan, Xianyong; Lei, Chuzhao; Zhao, Xin; Chen, Hong

2014-01-01

Background Adipose tissue has long been recognized to play an extremely important role in development. In bovines, it not only serves a fundamental function but also plays a key role in the quality of beef and, consequently, has drawn much public attention. Age and sex are two key factors that affect the development of adipose tissue, and there has not yet been a global study detailing the effects of these two factors on expressional differences of adipose tissues. Results In this study, total RNA from the back fat of fetal bovines, adult bulls, adult heifers and adult steers were used to construct libraries for Illumina next-generation sequencing. We detected the expression levels of 12,233 genes, with over 3,000 differently expressed genes when comparing fetal and adult patterns and an average of 1000 differently expressed genes when comparing adult patterns. Multiple Gene Ontology terms and pathways were found to be significantly enriched for these differentially expressed genes. Of the 12,233 detected genes, a total of 4,753 genes (38.85%) underwent alternative splicing events, and over 50% were specifically expressed in each library. Over 4,000 novel transcript units were discovered for one library, whereas only approximately 30% were considered to have coding ability, which supplied a large amount of information for the lncRNA study. Additionally, we detected 56,564 (fetal bovine), 65,154 (adult bull), 78,061 (adult heifer) and 86,965 (adult steer) putative single nucleotide polymorphisms located in coding regions of the four pooled libraries. Conclusion Here, we present, for the first time, a complete dataset involving the spatial and temporal transcriptome of bovine adipose tissue using RNA-seq. These data will facilitate the understanding of the effects of age and sex on the development of adipose tissue and supply essential information towards further studies on the genomes of beef cattle and other related mammals. PMID:24983926

Post-Transcriptional Dysregulation by miRNAs Is Implicated in the Pathogenesis of Gastrointestinal Stromal Tumor [GIST

PubMed Central

Kelly, Lorna; Bryan, Kenneth; Kim, Su Young; Janeway, Katherine A.; Killian, J. Keith; Schildhaus, Hans-Ulrich; Miettinen, Markku; Helman, Lee; Meltzer, Paul S.; van de Rijn, Matt; Debiec-Rychter, Maria; O’Sullivan, Maureen

2013-01-01

In contrast to adult mutant gastrointestinal stromal tumors [GISTs], pediatric/wild-type GISTs remain poorly understood overall, given their lack of oncogenic activating tyrosine kinase mutations. These GISTs, with a predilection for gastric origin in female patients, show limited response to therapy with tyrosine kinase inhibitors and generally pursue a more indolent course, but still may prove fatal. Defective cellular respiration appears to underpin tumor development in these wild-type cases, which as a group lack expression of succinate dehydrogenase [SDH] B, a surrogate marker for respiratory chain metabolism. Yet, only a small subset of the wild-type tumors show mutations in the genes coding for the SDH subunits [SDHx]. To explore additional pathogenetic mechanisms in these wild-type GISTs, we elected to investigate post-transcriptional regulation of these tumors by conducting microRNA (miRNA) profiling of a mixed cohort of 73 cases including 18 gastric pediatric wild-type, 25 (20 gastric, 4 small bowel and 1 retroperitoneal) adult wild-type GISTs and 30 gastric adult mutant GISTs. By this approach we have identified distinct signatures for GIST subtypes which correlate tightly with clinico-pathological parameters. A cluster of miRNAs on 14q32 show strikingly different expression patterns amongst GISTs, a finding which appears to be explained at least in part by differential allelic methylation of this imprinted region. Small bowel and retroperitoneal wild-type GISTs segregate with adult mutant GISTs and express SDHB, while adult wild-type gastric GISTs are dispersed amongst adult mutant and pediatric wild-type cases, clustering in this situation on the basis of SDHB expression. Interestingly, global methylation analysis has recently similarly demonstrated that these wild-type, SDHB-immunonegative tumors show a distinct pattern compared with KIT and PDGFRA mutant tumors, which as a rule do express SDHB. All cases with Carney triad within our cohort cluster together tightly. PMID:23717541

Post-transcriptional dysregulation by miRNAs is implicated in the pathogenesis of gastrointestinal stromal tumor [GIST].

PubMed

Kelly, Lorna; Bryan, Kenneth; Kim, Su Young; Janeway, Katherine A; Killian, J Keith; Schildhaus, Hans-Ulrich; Miettinen, Markku; Helman, Lee; Meltzer, Paul S; van de Rijn, Matt; Debiec-Rychter, Maria; O'Sullivan, Maureen

2013-01-01

In contrast to adult mutant gastrointestinal stromal tumors [GISTs], pediatric/wild-type GISTs remain poorly understood overall, given their lack of oncogenic activating tyrosine kinase mutations. These GISTs, with a predilection for gastric origin in female patients, show limited response to therapy with tyrosine kinase inhibitors and generally pursue a more indolent course, but still may prove fatal. Defective cellular respiration appears to underpin tumor development in these wild-type cases, which as a group lack expression of succinate dehydrogenase [SDH] B, a surrogate marker for respiratory chain metabolism. Yet, only a small subset of the wild-type tumors show mutations in the genes coding for the SDH subunits [SDHx]. To explore additional pathogenetic mechanisms in these wild-type GISTs, we elected to investigate post-transcriptional regulation of these tumors by conducting microRNA (miRNA) profiling of a mixed cohort of 73 cases including 18 gastric pediatric wild-type, 25 (20 gastric, 4 small bowel and 1 retroperitoneal) adult wild-type GISTs and 30 gastric adult mutant GISTs. By this approach we have identified distinct signatures for GIST subtypes which correlate tightly with clinico-pathological parameters. A cluster of miRNAs on 14q32 show strikingly different expression patterns amongst GISTs, a finding which appears to be explained at least in part by differential allelic methylation of this imprinted region. Small bowel and retroperitoneal wild-type GISTs segregate with adult mutant GISTs and express SDHB, while adult wild-type gastric GISTs are dispersed amongst adult mutant and pediatric wild-type cases, clustering in this situation on the basis of SDHB expression. Interestingly, global methylation analysis has recently similarly demonstrated that these wild-type, SDHB-immunonegative tumors show a distinct pattern compared with KIT and PDGFRA mutant tumors, which as a rule do express SDHB. All cases with Carney triad within our cohort cluster together tightly.

Characterization and expression profiling of serine protease inhibitors in the diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae).

PubMed

Lin, Hailan; Lin, Xijian; Zhu, Jiwei; Yu, Xiao-Qiang; Xia, Xiaofeng; Yao, Fengluan; Yang, Guang; You, Minsheng

2017-02-14

Serine protease inhibitors (SPIs) have been found in all living organisms and play significant roles in digestion, development and innate immunity. In this study, we present a genome-wide identification and expression profiling of SPI genes in the diamondback moth, Plutella xylostella (L.), a major pest of cruciferous crops with global distribution and broad resistance to different types of insecticides. A total of 61 potential SPI genes were identified in the P. xylostella genome, and these SPIs were classified into serpins, canonical inhibitors, and alpha-2-macroglobulins based on their modes of action. Sequence alignments showed that amino acid residues in the hinge region of known inhibitory serpins from other insect species were conserved in most P. xylostella serpins, suggesting that these P. xylostella serpins may be functionally active. Phylogenetic analysis confirmed that P. xylostella inhibitory serpins were clustered with known inhibitory serpins from six other insect species. More interestingly, nine serpins were highly similar to the orthologues in Manduca sexta which have been demonstrated to participate in regulating the prophenoloxidase activation cascade, an important innate immune response in insects. Of the 61 P.xylostella SPI genes, 33 were canonical SPIs containing seven types of inhibitor domains, including Kunitz, Kazal, TIL, amfpi, Antistasin, WAP and Pacifastin. Moreover, some SPIs contained additional non-inhibitor domains, including spondin_N, reeler, and other modules, which may be involved in protein-protein interactions. Gene expression profiling showed gene-differential, stage- and sex-specific expression patterns of SPIs, suggesting that SPIs may be involved in multiple physiological processes in P. xylostella. This is the most comprehensive investigation so far on SPI genes in P. xylostella. The characterized features and expression patterns of P. xylostella SPIs indicate that the SPI family genes may be involved in innate immunity of this species. Our findings provide valuable information for uncovering further biological roles of SPI genes in P. xylostella.

Research in geosciences policy

NASA Technical Reports Server (NTRS)

Byerly, Radford, Jr.; Mcvey, Sally

1991-01-01

Various topics related to cases of difficult adaptation to global change are discussed. Topics include patterns in the ratification of global environmental treaties, the effects of global climate change on Southeast Asia, and global change and biodiversity loss.

Estimation of Global 1km-grid Terrestrial Carbon Exchange Part II: Evaluations and Applications

NASA Astrophysics Data System (ADS)

Murakami, K.; Sasai, T.; Kato, S.; Niwa, Y.; Saito, M.; Takagi, H.; Matsunaga, T.; Hiraki, K.; Maksyutov, S. S.; Yokota, T.

2015-12-01

Global terrestrial carbon cycle largely depends on a spatial pattern in land cover type, which is heterogeneously-distributed over regional and global scales. Many studies have been trying to reveal distribution of carbon exchanges between terrestrial ecosystems and atmosphere for understanding global carbon cycle dynamics by using terrestrial biosphere models, satellite data, inventory data, and so on. However, most studies remained within several tens of kilometers grid spatial resolution, and the results have not been enough to understand the detailed pattern of carbon exchanges based on ecological community and to evaluate the carbon stocks by forest ecosystems in each countries. Improving the sophistication of spatial resolution is obviously necessary to enhance the accuracy of carbon exchanges. Moreover, the improvement may contribute to global warming awareness, policy makers and other social activities. We show global terrestrial carbon exchanges (net ecosystem production, net primary production, and gross primary production) with 1km-grid resolution. The methodology for these estimations are shown in the 2015 AGU FM poster "Estimation of Global 1km-grid Terrestrial Carbon Exchange Part I: Developing Inputs and Modelling". In this study, we evaluated the carbon exchanges in various regions with other approaches. We used the satellite-driven biosphere model (BEAMS) as our estimations, GOSAT L4A CO2 flux data, NEP retrieved by NICAM and CarbonTracer2013 flux data, for period from Jun 2001 to Dec 2012. The temporal patterns for this period were indicated similar trends between BEAMS, GOSAT, NICAM, and CT2013 in many sub-continental regions. Then, we estimated the terrestrial carbon exchanges in each countries, and could indicated the temporal patterns of the exchanges in large carbon stock regions.Global terrestrial carbon cycle largely depends on a spatial pattern of land cover type, which is heterogeneously-distributed over regional and global scales. Many studies have been trying to reveal distribution of carbon exchanges between terrestrial ecosystems and atmosphere for understanding global carbon cycle dynamics by using terrestrial biosphere models, satellite data, inventory data, and so on. However, most studies remained within several tens of kilometers grid spatial resolution, and the results have not been enough to understand the detailed pattern of carbon exchanges based on ecological community and to evaluate the carbon stocks by forest ecosystems in each countries. Improving the sophistication of spatial resolution is obviously necessary to enhance the accuracy of carbon exchanges. Moreover, the improvement may contribute to global warming awareness, policy makers and other social activities. We show global terrestrial carbon exchanges (net ecosystem production, net primary production, and gross primary production) with 1km-grid resolution. The methodology for these estimations are shown in the 2015 AGU FM poster "Estimation of Global 1km-grid Terrestrial Carbon Exchange Part I: Developing Inputs and Modelling". In this study, we evaluated the carbon exchanges in various regions with other approaches. We used the satellite-driven biosphere model (BEAMS) as our estimations, GOSAT L4A CO2 flux data, NEP retrieved by NICAM and CarbonTracer2013 flux data, for period from Jun 2001 to Dec 2012. The temporal patterns for this period were indicated similar trends between BEAMS, GOSAT, NICAM, and CT2013 in many sub-continental regions. Then, we estimated the terrestrial carbon exchanges in each countries, and could indicated the temporal patterns of the exchanges in large carbon stock regions.

Analyzing Global Components in Developmental Dyscalculia and Dyslexia

PubMed Central

Filippo, Gloria Di; Zoccolotti, Pierluigi

2018-01-01

The study examined whether developmental deficits in reading and numerical skills could be expressed in terms of global factors by reference to the rate and amount (RAM) and difference engine (DEM) models. From a sample of 325 fifth grade children, we identified 5 children with dyslexia, 16 with dyscalculia, 7 with a “mixed pattern,” and 49 control children. Children were asked to read aloud words presented individually that varied for frequency and length and to respond (either vocally or manually) to a series of simple number tasks (addition, subtraction, number reading, and number comparisons). Reaction times were measured. Results indicated that the deficit of children with dyscalculia and children with a mixed pattern on numerical tasks could be explained by a single global factor, similarly to the reading deficit shown by children with dyslexia. As predicted by the DEM, increases in task difficulty were accompanied by a corresponding increase in inter-individual variability for both the reading and numerical tasks. These relationships were constant across the four groups of children but differed in terms of slope and intercept on the x-axis, indicating that two different general rules underlie performance in reading and numerical skills. The study shows for the first time that, as previously shown for reading, also numerical performance can be explained with reference to a global factor. The advantage of this approach is that it takes into account the over-additivity effect, i.e., the presence of larger group differences in the case of more difficult conditions over and above the characteristics of the experimental conditions. It is concluded that reference to models such as the RAM and DEM can be useful in delineating the characteristics of the dyscalculic deficit as well as in the description of co-morbid disturbances, as in the case of dyslexia and dyscalculia. PMID:29515490

A multiyear, global gridded fossil fuel CO2 emission data product: Evaluation and analysis of results

NASA Astrophysics Data System (ADS)

Asefi-Najafabady, S.; Rayner, P. J.; Gurney, K. R.; McRobert, A.; Song, Y.; Coltin, K.; Huang, J.; Elvidge, C.; Baugh, K.

2014-09-01

High-resolution, global quantification of fossil fuel CO2 emissions is emerging as a critical need in carbon cycle science and climate policy. We build upon a previously developed fossil fuel data assimilation system (FFDAS) for estimating global high-resolution fossil fuel CO2 emissions. We have improved the underlying observationally based data sources, expanded the approach through treatment of separate emitting sectors including a new pointwise database of global power plants, and extended the results to cover a 1997 to 2010 time series at a spatial resolution of 0.1°. Long-term trend analysis of the resulting global emissions shows subnational spatial structure in large active economies such as the United States, China, and India. These three countries, in particular, show different long-term trends and exploration of the trends in nighttime lights, and population reveal a decoupling of population and emissions at the subnational level. Analysis of shorter-term variations reveals the impact of the 2008-2009 global financial crisis with widespread negative emission anomalies across the U.S. and Europe. We have used a center of mass (CM) calculation as a compact metric to express the time evolution of spatial patterns in fossil fuel CO2 emissions. The global emission CM has moved toward the east and somewhat south between 1997 and 2010, driven by the increase in emissions in China and South Asia over this time period. Analysis at the level of individual countries reveals per capita CO2 emission migration in both Russia and India. The per capita emission CM holds potential as a way to succinctly analyze subnational shifts in carbon intensity over time. Uncertainties are generally lower than the previous version of FFDAS due mainly to an improved nightlight data set.

Mars Express Seen by Mars Global Surveyor

NASA Image and Video Library

2005-05-19

This picture of the European Space Agency Mars Express spacecraft by the Mars Orbiter Camera on NASA Mars Global Surveyor is from the first successful imaging of any spacecraft orbiting Mars taken by another spacecraft orbiting Mars.

Expression of Eag1 K+ channel and ErbBs in human pituitary adenomas: cytoskeleton arrangement patterns in cultured cells.

PubMed

del Pliego, Margarita González; Aguirre-Benítez, Elsa; Paisano-Cerón, Karina; Valdovinos-Ramírez, Irene; Rangel-Morales, Carlos; Rodríguez-Mata, Verónica; Solano-Agama, Carmen; Martín-Tapia, Dolores; de la Vega, María Teresa; Saldoval-Balanzario, Miguel; Camacho, Javier; Mendoza-Garrido, María Eugenia

2013-01-01

Pituitary adenomas can invade surrounded tissue, but the mechanism remains elusive. Ether à go-go-1 (Eag1) potassium channel and epidermal growth factor receptors (ErbB1 and ErbB2) have been associated to invasive phenotypes or poor prognosis in cancer patients. However, cells arrange their cytoskeleton in order to acquire a successful migration pattern. We have studied ErbBs and Eag1 expression, and cytoskeleton arrangements in 11 human pituitary adenomas. Eag1, ErbB1 and ErbB2 expression were studied by immunochemistry in tissue and cultured cells. The cytoskeleton arrangement was analyzed in cultured cells by immunofluorescence. Normal pituitary tissue showed ErbB2 expression and Eag1 only in few cells. However, Eag1 and ErbB2 were expressed in all the tumors analyzed. ErbB1 expression was observed variable and did not show specificity for a tumor characteristic. Cultured cells from micro- and macro-adenomas clinically functional organize their cytoskeleton suggesting a mesenchymal pattern, and a round leucocyte/amoeboid pattern from invasive clinically silent adenoma. Pituitary tumors over-express EGF receptors and the ErbB2 repeated expression suggests is a characteristic of adenomas. Eag 1 was express, in different extent, and could be a therapeutic target. The cytoskeleton arrangements observed suggest that pituitary tumor cells acquire different patterns: mesenchymal, and leucocyte/amoeboid, the last observed in the invasive adenomas. Amoeboid migration pattern has been associated with high invasion capacity.

Global-scale modes of surface temperature variability on interannual to century timescales

NASA Technical Reports Server (NTRS)

Mann, Michael E.; Park, Jeffrey

1994-01-01

Using 100 years of global temperature anomaly data, we have performed a singluar value decomposition of temperature variations in narrow frequency bands to isolate coherent spatio-temporal modes of global climate variability. Statistical significance is determined from confidence limits obtained by Monte Carlo simulations. Secular variance is dominated by a globally coherent trend; with nearly all grid points warming in phase at varying amplitude. A smaller, but significant, share of the secular variance corresponds to a pattern dominated by warming and subsequent cooling in the high latitude North Atlantic with a roughly centennial timescale. Spatial patterns associated with significant peaks in variance within a broad period range from 2.8 to 5.7 years exhibit characteristic El Nino-Southern Oscillation (ENSO) patterns. A recent transition to a regime of higher ENSO frequency is suggested by our analysis. An interdecadal mode in the 15-to-18 years period and a mode centered at 7-to-8 years period both exhibit predominantly a North Atlantic Oscillation (NAO) temperature pattern. A potentially significant decadal mode centered on 11-to-12 years period also exhibits an NAO temperature pattern and may be modulated by the century-scale North Atlantic variability.

Anthropogenic Transformation of the Biomes, 1700 to 2000

NASA Astrophysics Data System (ADS)

Ellis, E. C.; Lightman, D.; Klein Goldewijk, K.; Ramankutty, N.

2008-12-01

Current global patterns of terrestrial ecosystem form and process are now predominantly anthropogenic as a result of land use and other direct human interactions with ecosystems. This study investigates anthropogenic transformation of the terrestrial biosphere over the course of the industrial revolution by mapping and characterizing global transitions between wild and anthropogenic biomes between 1700 and 2000. A global map of potential natural vegetation was used to represent wild biomes. Anthropogenic biomes were mapped for 1700, 1800, 1900 and 2000 using rule-based classification of current and historical global data for human population density, urban area and percent land cover by cultivated crops (rainfed, irrigated, and rice) and pastures. By assuming that wild, climate-driven, biome patterns have been relatively constant since 1700, transitions between wild and anthropogenic biomes were characterized between 1700 and 2000 at century intervals. Historical analysis of wild to anthropogenic biome transitions reveal the global transition from a primarily wild to a primarily anthropogenic terrestrial biosphere. Moreover, by mapping and examining global transitions between wild and anthropogenic biome classes, we provide a simple framework for assessing and modeling both past and future global biotic and ecological patterns in the light of the extent, intensity and duration of their modification by humans.

Genomic Expression Patterns in Menstrually-Related Migraine in Adolescents

PubMed Central

Hershey, Andrew; Horn, Paul; Kabbouche, Marielle; O'Brien, Hope; Powers, Scott

2011-01-01

Background Exacerbation of migraine with menses is common in adolescent girls and women with migraine, occurring in up to 60% of females with migraine. These migraines are oftentimes longer and more disabling and may be related to estrogen levels and hormonal fluctuations. Objective This study identifies the unique genomic expression pattern of menstrually-related migraine (MRM) in comparison to migraine occurring outside the menstrual period and headache free controls. Methods Whole blood samples were obtained from female subjects having an acute migraine during their menstrual period (MRM) or outside of their menstrual period (nonMRM) and controls (C) – females having a menstrual period without any history of headache. The mRNA was isolated from these samples and genomic profile was assessed. Affymetrix Human Exon ST 1.0 arrays were used to examine the genomic expression pattern differences between these three groups. Results Blood genomic expression patterns were obtained on 56 subjects (MRM = 18, nonMRM = 18 and C = 20). Unique genomic expression patterns were observed for both MRM and nonMRM. For MRM, 77 genes were identified that were unique to MRM, while 61 genes were commonly expressed for MRM and nonMRM and 127 genes appeared to have a unique expression pattern for nonMRM. In addition, there were 279 genes that differentially expressed for MRM compared to nonMRM that were not differentially expressed for nonMRM. Gene ontology of these samples indicated many of these groups of genes were functionally related and included categories of immunomodulation/inflammation, mitochondrial function and DNA homeostasis. Conclusions Blood genomic patterns can accurately differentiate MRM from nonMRM. These results indicate that MRM involves a unique molecular biology pathway that can be identified with a specific biomarker and suggest that individuals with MRM have a different underlying genetic etiology. PMID:22220971

The Glycolytic Versatility of Bacteroides uniformis CECT 7771 and Its Genome Response to Oligo and Polysaccharides

PubMed Central

Benítez-Páez, Alfonso; Gómez del Pulgar, Eva M.; Sanz, Yolanda

2017-01-01

Bacteroides spp. are dominant components of the phylum Bacteroidetes in the gut microbiota and prosper in glycan enriched environments. However, knowledge of the machinery of specific species isolated from humans (like Bacteroides uniformis) contributing to the utilization of dietary and endogenous sources of glycans and their byproducts is limited. We have used the cutting-edge nanopore-based technology to sequence the genome of B. uniformis CECT 7771, a human symbiont with a proven pre-clinical efficacy on metabolic and immune dysfunctions in obesity animal models. We have also used massive sequencing approaches to distinguish the genome expression patterns in response to carbon sources of different complexity during growth. At genome-wide level, our analyses globally demonstrate that B. uniformis strains exhibit an expanded glycolytic capability when compared with other Bacteroides species. Moreover, by studying the growth and whole-genome expression of B. uniformis CECT 7771 in response to different carbon sources, we detected a differential growth fitness and expression patterns across the genome depending on the carbon source of the culture media. The dietary fibers used exerted different effects on B. uniformis CECT 7771 activating different molecular pathways and, therefore, allowing the production of different metabolite types with potential impact on gut health. The genome and transcriptome analysis of B. uniformis CECT 7771, in response to different carbon sources, shows its high versatility to utilize both dietary and endogenous glycans along with the production of potentially beneficial end products for both the bacterium and the host, pointing to a mechanistic basis of a mutualistic relationship. PMID:28971068

Osterix/Sp7 limits cranial bone initiation sites and is required for formation of sutures

PubMed Central

Kague, Erika; Roy, Paula; Asselin, Garrett; Hu, Gui; Stanley, Alexandra; Albertson, Craig; Simonet, Jacqueline; Fisher, Shannon

2017-01-01

During growth, individual skull bones overlap at sutures, where osteoblast differentiation and bone deposition occur. Mutations causing skull malformations have revealed some required genes, but many aspects of suture regulation remain poorly understood. We describe a zebrafish mutation in osterix/sp7, which causes a generalized delay in osteoblast maturation. While most of the skeleton is patterned normally, mutants have specific defects in the anterior skull and upper jaw, and the top of the skull comprises a random mosaic of bones derived from individual initiation sites. Osteoblasts at the edges of the bones are highly proliferative and fail to differentiate, consistent with global changes in gene expression. We propose that signals from the bone itself are required for orderly recruitment of precursor cells and growth along the edges. The delay in bone maturation caused by loss of Sp7 leads to unregulated bone formation, revealing a new mechanism for patterning the skull and sutures. PMID:26992365

Internal Characteristics of Phobos and Deimos from Spectral Properties and Density: Relationship to Landforms and Comparison with Asteroids

NASA Technical Reports Server (NTRS)

Murchie, S. L.; Fraeman, A. A.; Arvidson, R. E.; Rivkin, A. S.; Morris, R. V.

2013-01-01

Compositional interpretations of new spectral measurements of Phobos and Deimos from Mars Express/OMEGA and MRO/CRISM and density measurements from encounters by multiple spacecraft support refined estimates of the moons' porosity and internal structure. Phobos' estimated macroporosity of 12-20% is consistent with a fractured but coherent interior; Deimos' estimated macroporosity of 23-44% is more consistent with a loosely consolidated interior. These internal differences are reflected in differences in surface morphology: Phobos exhibits a globally coherent pattern of grooves, whereas Deimos has a surface dominated instead by fragmental debris. Comparison with other asteroids .110 km in diameter shows that this correspondence between landforms and inferred internal structure is part of a pervasive pattern: asteroids interpreted to have coherent interiors exhibit pervasive, organized ridge or groove systems, whereas loosely consolidated asteroids have landforms dominated by fragmental debris and/or retain craters >1.3 body radii in diameter suggesting a porous, compressible interior.

Exposure to air pollution interacts with obesogenic nutrition to induce tissue-specific response patterns.

PubMed

Pardo, Michal; Kuperman, Yael; Levin, Liron; Rudich, Assaf; Haim, Yulia; Schauer, James J; Chen, Alon; Rudich, Yinon

2018-04-20

Obesity and exposure to particular matter (PM) have become two leading global threats to public health. However, the exact mechanisms and tissue-specificity of their health effects are largely unknown. Here we investigate whether a metabolic challenge (early nutritional obesity) synergistically interacts with an environmental challenge (PM exposure) to alter genes representing key response pathways, in a tissue-specific manner. Mice subjected to 7 weeks obesogenic nutrition were exposed every other day during the final week and a half to aqueous extracts of PM collected in the city of London (UK). The expression of 61 selected genes representing key response pathways were investigated in lung, liver, white and brown adipose tissues. Principal component analysis (PCA) revealed distinct patterns of expression changes between the 4 tissues, particularly in the lungs and the liver. Surprisingly, the lung responded to the nutrition challenge. The response of these organs to the PM challenge displayed opposite patterns for some key genes, in particular, those related to the Nrf2 pathway. While the contribution to the variance in gene expression changes in mice exposed to the combined challenge were largely similar among the tissues in PCA1, PCA2 exhibited predominant contribution of inflammatory and oxidative stress responses to the variance in the lungs, and a greater contribution of autophagy genes and MAP kinases in adipose tissues. Possible involvement of alterations in DNA methylation was demonstrated by cell-type-specific responses to a methylation inhibitor. Correspondingly, the DNA methyltransferase Dnmt3a2 increased in the lungs but decreased in the liver, demonstrating potential tissue-differential synergism between nutritional and PM exposure. The results suggest that urban PM, containing dissolved metals, interacts with obesogenic nutrition to regulate diverse response pathways including inflammation and oxidative stress, in a tissue-specific manner. Tissue-differential effects on DNA methylation may underlie tissue-specific responses to key stress-response genes such as catalase and Nrf2. Copyright © 2018 Elsevier Ltd. All rights reserved.

Regulatory analysis of the mouse Hoxb3 gene: multiple elements work in concert to direct temporal and spatial patterns of expression.

PubMed

Kwan, C T; Tsang, S L; Krumlauf, R; Sham, M H

2001-04-01

The expression pattern of the mouse Hoxb3 gene is exceptionally complex and dynamic compared with that of other members of the Hoxb cluster. There are multiple types of transcripts for Hoxb3 gene, and the anterior boundaries of its expression vary at different stages of development. Two enhancers flanking Hoxb3 on the 3' and 5' sides regulate Hoxb2 and Hoxb4, respectively, and these control regions define the two ends of a 28-kb interval in and around the Hoxb3 locus. To assay the regulatory potential of DNA fragments in this interval we have used transgenic analysis with a lacZ reporter gene to locate cis-elements for directing the dynamic patterns of Hoxb3 expression. Our detailed analysis has identified four new and widely spaced cis-acting regulatory regions that can together account for major aspects of the Hoxb3 expression pattern. Elements Ib, IIIa, and IVb control gene expression in neural and mesodermal tissues; element Va controls mesoderm-specific gene expression. The most anterior neural expression domain of Hoxb3 is controlled by an r5 enhancer (element IVa); element IIIa directs reporter expression in the anterior spinal cord and hindbrain up to r6, and the region A enhancer (in element I) mediates posterior neural expression. Hence, the regulation of segmental expression of Hoxb3 in the hindbrain is different from that of Hoxa3, as two separate enhancer elements contribute to expression in r5 and r6. The mesoderm-specific element (Va) directs reporter expression to prevertebra C1 at 12.5 dpc, which is the anterior limit of paraxial mesoderm expression for Hoxb3. When tested in combinations, these cis-elements appear to work as modules in an additive manner to recapitulate the major endogenous expression patterns of Hoxb3 during embryogenesis. Together our study shows that multiple control elements direct reporter gene expression in diverse tissue-, temporal-, and spatially restricted subset of the endogenous Hoxb3 expression domains and work in concert to control the neural and mesodermal patterns of expression. Copyright 2001 Academic Press.

Epigenetic regulation of serotype expression antagonizes transcriptome dynamics in Paramecium tetraurelia.

PubMed

Cheaib, Miriam; Dehghani Amirabad, Azim; Nordström, Karl J V; Schulz, Marcel H; Simon, Martin

2015-08-01

Phenotypic variation of a single genotype is achieved by alterations in gene expression patterns. Regulation of such alterations depends on their time scale, where short-time adaptations differ from permanently established gene expression patterns maintained by epigenetic mechanisms. In the ciliate Paramecium, serotypes were described for an epigenetically controlled gene expression pattern of an individual multigene family. Paradoxically, individual serotypes can be triggered in Paramecium by alternating environments but are then stabilized by epigenetic mechanisms, thus raising the question to which extend their expression follows environmental stimuli. To characterize environmental adaptation in the context of epigenetically controlled serotype expression, we used RNA-seq to characterize transcriptomes of serotype pure cultures. The resulting vegetative transcriptome resource is first analysed for genes involved in the adaptive response to the altered environment. Secondly, we identified groups of genes that do not follow the adaptive response but show co-regulation with the epigenetically controlled serotype system, suggesting that their gene expression pattern becomes manifested by similar mechanisms. In our experimental set-up, serotype expression and the entire group of co-regulated genes were stable among environmental changes and only heat-shock genes altered expression of these gene groups. The data suggest that the maintenance of these gene expression patterns in a lineage represents epigenetically controlled robustness counteracting short-time adaptation processes. © The Author 2015. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

Gene expression profiles in peripheral blood mononuclear cells of Chinese nickel refinery workers with high exposures to nickel and control subjects

PubMed Central

Arita, Adriana; Muñoz, Alexandra; Chervona, Yana; Niu, Jingping; Qu, Qingshan; Zhao, Najuan; Ruan, Ye; Kiok, Kathrin; Kluz, Thomas; Sun, Hong; Clancy, Hailey A.; Shamy, Magdy; Costa, Max

2012-01-01

Background Occupational exposure to nickel (Ni) is associated with an increased risk of lung and nasal cancers. Ni compounds exhibit weak mutagenic activity, alter the cell’s epigenetic homeostasis, and activate signaling pathways. However, changes in gene expression associated with Ni exposure have only been investigated in vitro. This study was conducted in a Chinese population to determine whether occupational exposure to Ni was associated with differential gene expression profiles in the peripheral blood mononuclear cells (PBMCs) of Ni-refinery workers when compared to referents. Methods Eight Ni-refinery workers and ten referents were selected. PBMC RNA was extracted and gene expression profiling was performed using Affymetrix exon arrays. Differentially expressed genes between both groups were identified in a global analysis. Results There were a total of 2756 differentially expressed genes (DEG) in the Ni-refinery workers relative to the control subjects (FDR adjusted p<0.05) with 770 up-regulated genes and 1986 down-regulated genes. DNA repair and epigenetic genes were significantly overrepresented (p< 0.0002) among the DEG. Of 31 DNA repair genes, 29 were repressed in the high exposure group and two were overexpressed. Of the 16 epigenetic genes 12 were repressed in the high exposure group and 4 were overexpressed. Conclusions The results of this study indicate that occupational exposure to Ni is associated with alterations in gene expression profiles in PBMCs of subjects. Impact Gene expression may be useful in identifying patterns of deregulation that precede clinical identification of Ni-induced cancers. PMID:23195993

MicroRNA Expression Profiles in Cultured Human Fibroblasts in Space

NASA Technical Reports Server (NTRS)

Wu, Honglu; Lu, Tao; Jeevarajan, John; Rohde, Larry; Zhang, Ye

2014-01-01

Microgravity, or an altered gravity environment from the static 1g, has been shown to influence global gene expression patterns and protein levels in living organisms. However, it is unclear how these changes in gene and protein expressions are related to each other or are related to other factors regulating such changes. A different class of RNA, the small non-coding microRNA (miRNA), can have a broad effect on gene expression networks by mainly inhibiting the translation process. Previously, we investigated changes in the expression of miRNA and related genes under simulated microgravity conditions on the ground using the NASA invented bioreactor. In comparison to static 1 g, simulated microgravity altered a number of miRNAs in human lymphoblastoid cells. Pathway analysis with the altered miRNAs and RNA expressions revealed differential involvement of cell communication and catalytic activity, as well as immune response signaling and NGF activation of NF-kB pathways under simulated microgravity condition. The network analysis also identified several projected networks with c- Rel, ETS1 and Ubiquitin C as key factors. In a flight experiment on the International Space Station (ISS), we will investigate the effects of actual spaceflight on miRNA expressions in nondividing human fibroblast cells in mostly G1 phase of the cell cycle. A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for tissues, and plays a critical role in wound healing and other functions. In addition to miRNA expressions, we will investigate the effects of spaceflight on the cellular response to DNA damages from bleomycin treatment.

Study on Global GIS architecture and its key technologies

NASA Astrophysics Data System (ADS)

Cheng, Chengqi; Guan, Li; Lv, Xuefeng

2009-09-01

Global GIS (G2IS) is a system, which supports the huge data process and the global direct manipulation on global grid based on spheroid or ellipsoid surface. Based on global subdivision grid (GSG), Global GIS architecture is presented in this paper, taking advantage of computer cluster theory, the space-time integration technology and the virtual reality technology. Global GIS system architecture is composed of five layers, including data storage layer, data representation layer, network and cluster layer, data management layer and data application layer. Thereinto, it is designed that functions of four-level protocol framework and three-layer data management pattern of Global GIS based on organization, management and publication of spatial information in this architecture. Three kinds of core supportive technologies, which are computer cluster theory, the space-time integration technology and the virtual reality technology, and its application pattern in the Global GIS are introduced in detail. The primary ideas of Global GIS in this paper will be an important development tendency of GIS.

Study on Global GIS architecture and its key technologies

NASA Astrophysics Data System (ADS)

Cheng, Chengqi; Guan, Li; Lv, Xuefeng

2010-11-01

Global GIS (G2IS) is a system, which supports the huge data process and the global direct manipulation on global grid based on spheroid or ellipsoid surface. Based on global subdivision grid (GSG), Global GIS architecture is presented in this paper, taking advantage of computer cluster theory, the space-time integration technology and the virtual reality technology. Global GIS system architecture is composed of five layers, including data storage layer, data representation layer, network and cluster layer, data management layer and data application layer. Thereinto, it is designed that functions of four-level protocol framework and three-layer data management pattern of Global GIS based on organization, management and publication of spatial information in this architecture. Three kinds of core supportive technologies, which are computer cluster theory, the space-time integration technology and the virtual reality technology, and its application pattern in the Global GIS are introduced in detail. The primary ideas of Global GIS in this paper will be an important development tendency of GIS.

BMPs regulate msx gene expression in the dorsal neuroectoderm of Drosophila and vertebrates by distinct mechanisms.

PubMed

Esteves, Francisco F; Springhorn, Alexander; Kague, Erika; Taylor, Erika; Pyrowolakis, George; Fisher, Shannon; Bier, Ethan

2014-09-01

In a broad variety of bilaterian species the trunk central nervous system (CNS) derives from three primary rows of neuroblasts. The fates of these neural progenitor cells are determined in part by three conserved transcription factors: vnd/nkx2.2, ind/gsh and msh/msx in Drosophila melanogaster/vertebrates, which are expressed in corresponding non-overlapping patterns along the dorsal-ventral axis. While this conserved suite of "neural identity" gene expression strongly suggests a common ancestral origin for the patterning systems, it is unclear whether the original regulatory mechanisms establishing these patterns have been similarly conserved during evolution. In Drosophila, genetic evidence suggests that Bone Morphogenetic Proteins (BMPs) act in a dosage-dependent fashion to repress expression of neural identity genes. BMPs also play a dose-dependent role in patterning the dorsal and lateral regions of the vertebrate CNS, however, the mechanism by which they achieve such patterning has not yet been clearly established. In this report, we examine the mechanisms by which BMPs act on cis-regulatory modules (CRMs) that control localized expression of the Drosophila msh and zebrafish (Danio rerio) msxB in the dorsal central nervous system (CNS). Our analysis suggests that BMPs act differently in these organisms to regulate similar patterns of gene expression in the neuroectoderm: repressing msh expression in Drosophila, while activating msxB expression in the zebrafish. These findings suggest that the mechanisms by which the BMP gradient patterns the dorsal neuroectoderm have reversed since the divergence of these two ancient lineages.