Toward a Periodic Table of Niches, or Exploring the Lizard Niche Hypervolume.

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Pianka, Eric R; Vitt, Laurie J; Pelegrin, Nicolás; Fitzgerald, Daniel B; Winemiller, Kirk O

2017-11-01

Widespread niche convergence suggests that species can be organized according to functional trait combinations to create a framework analogous to a periodic table. We compiled ecological data for lizards to examine patterns of global and regional niche diversification, and we used multivariate statistical approaches to develop the beginnings for a periodic table of niches. Data (50+ variables) for five major niche dimensions (habitat, diet, life history, metabolism, defense) were compiled for 134 species of lizards representing 24 of the 38 extant families. Principal coordinates analyses were performed on niche dimensional data sets, and species scores for the first three axes were used as input for a principal components analysis to ordinate species in continuous niche space and for a regression tree analysis to separate species into discrete niche categories. Three-dimensional models facilitate exploration of species positions in relation to major gradients within the niche hypervolume. The first gradient loads on body size, foraging mode, and clutch size. The second was influenced by metabolism and terrestrial versus arboreal microhabitat. The third was influenced by activity time, life history, and diet. Natural dichotomies are activity time, foraging mode, parity mode, and habitat. Regression tree analysis identified 103 cases of extreme niche conservatism within clades and 100 convergences between clades. Extending this approach to other taxa should lead to a wider understanding of niche evolution.

IGSA: Individual Gene Sets Analysis, including Enrichment and Clustering.

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Wu, Lingxiang; Chen, Xiujie; Zhang, Denan; Zhang, Wubing; Liu, Lei; Ma, Hongzhe; Yang, Jingbo; Xie, Hongbo; Liu, Bo; Jin, Qing

2016-01-01

Analysis of gene sets has been widely applied in various high-throughput biological studies. One weakness in the traditional methods is that they neglect the heterogeneity of genes expressions in samples which may lead to the omission of some specific and important gene sets. It is also difficult for them to reflect the severities of disease and provide expression profiles of gene sets for individuals. We developed an application software called IGSA that leverages a powerful analytical capacity in gene sets enrichment and samples clustering. IGSA calculates gene sets expression scores for each sample and takes an accumulating clustering strategy to let the samples gather into the set according to the progress of disease from mild to severe. We focus on gastric, pancreatic and ovarian cancer data sets for the performance of IGSA. We also compared the results of IGSA in KEGG pathways enrichment with David, GSEA, SPIA, ssGSEA and analyzed the results of IGSA clustering and different similarity measurement methods. Notably, IGSA is proved to be more sensitive and specific in finding significant pathways, and can indicate related changes in pathways with the severity of disease. In addition, IGSA provides with significant gene sets profile for each sample.

Zebrafish Expression Ontology of Gene Sets (ZEOGS): A Tool to Analyze Enrichment of Zebrafish Anatomical Terms in Large Gene Sets

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Marsico, Annalisa

2013-01-01

Abstract The zebrafish (Danio rerio) is an established model organism for developmental and biomedical research. It is frequently used for high-throughput functional genomics experiments, such as genome-wide gene expression measurements, to systematically analyze molecular mechanisms. However, the use of whole embryos or larvae in such experiments leads to a loss of the spatial information. To address this problem, we have developed a tool called Zebrafish Expression Ontology of Gene Sets (ZEOGS) to assess the enrichment of anatomical terms in large gene sets. ZEOGS uses gene expression pattern data from several sources: first, in situ hybridization experiments from the Zebrafish Model Organism Database (ZFIN); second, it uses the Zebrafish Anatomical Ontology, a controlled vocabulary that describes connected anatomical structures; and third, the available connections between expression patterns and anatomical terms contained in ZFIN. Upon input of a gene set, ZEOGS determines which anatomical structures are overrepresented in the input gene set. ZEOGS allows one for the first time to look at groups of genes and to describe them in terms of shared anatomical structures. To establish ZEOGS, we first tested it on random gene selections and on two public microarray datasets with known tissue-specific gene expression changes. These tests showed that ZEOGS could reliably identify the tissues affected, whereas only very few enriched terms to none were found in the random gene sets. Next we applied ZEOGS to microarray datasets of 24 and 72 h postfertilization zebrafish embryos treated with beclomethasone, a potent glucocorticoid. This analysis resulted in the identification of several anatomical terms related to glucocorticoid-responsive tissues, some of which were stage-specific. Our studies highlight the ability of ZEOGS to extract spatial information from datasets derived from whole embryos, indicating that ZEOGS could be a useful tool to automatically analyze gene

Zebrafish Expression Ontology of Gene Sets (ZEOGS): a tool to analyze enrichment of zebrafish anatomical terms in large gene sets.

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Prykhozhij, Sergey V; Marsico, Annalisa; Meijsing, Sebastiaan H

2013-09-01

The zebrafish (Danio rerio) is an established model organism for developmental and biomedical research. It is frequently used for high-throughput functional genomics experiments, such as genome-wide gene expression measurements, to systematically analyze molecular mechanisms. However, the use of whole embryos or larvae in such experiments leads to a loss of the spatial information. To address this problem, we have developed a tool called Zebrafish Expression Ontology of Gene Sets (ZEOGS) to assess the enrichment of anatomical terms in large gene sets. ZEOGS uses gene expression pattern data from several sources: first, in situ hybridization experiments from the Zebrafish Model Organism Database (ZFIN); second, it uses the Zebrafish Anatomical Ontology, a controlled vocabulary that describes connected anatomical structures; and third, the available connections between expression patterns and anatomical terms contained in ZFIN. Upon input of a gene set, ZEOGS determines which anatomical structures are overrepresented in the input gene set. ZEOGS allows one for the first time to look at groups of genes and to describe them in terms of shared anatomical structures. To establish ZEOGS, we first tested it on random gene selections and on two public microarray datasets with known tissue-specific gene expression changes. These tests showed that ZEOGS could reliably identify the tissues affected, whereas only very few enriched terms to none were found in the random gene sets. Next we applied ZEOGS to microarray datasets of 24 and 72 h postfertilization zebrafish embryos treated with beclomethasone, a potent glucocorticoid. This analysis resulted in the identification of several anatomical terms related to glucocorticoid-responsive tissues, some of which were stage-specific. Our studies highlight the ability of ZEOGS to extract spatial information from datasets derived from whole embryos, indicating that ZEOGS could be a useful tool to automatically analyze gene expression

In silico analysis of stomach lineage specific gene set expression pattern in gastric cancer.

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Pandi, Narayanan Sathiya; Suganya, Sivagurunathan; Rajendran, Suriliyandi

2013-10-04

Stomach lineage specific gene products act as a protective barrier in the normal stomach and their expression maintains the normal physiological processes, cellular integrity and morphology of the gastric wall. However, the regulation of stomach lineage specific genes in gastric cancer (GC) is far less clear. In the present study, we sought to investigate the role and regulation of stomach lineage specific gene set (SLSGS) in GC. SLSGS was identified by comparing the mRNA expression profiles of normal stomach tissue with other organ tissue. The obtained SLSGS was found to be under expressed in gastric tumors. Functional annotation analysis revealed that the SLSGS was enriched for digestive function and gastric epithelial maintenance. Employing a single sample prediction method across GC mRNA expression profiles identified the under expression of SLSGS in proliferative type and invasive type gastric tumors compared to the metabolic type gastric tumors. Integrative pathway activation prediction analysis revealed a close association between estrogen-α signaling and SLSGS expression pattern in GC. Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. In conclusion, our results highlight that estrogen mediated regulation of SLSGS in gastric tumor is a molecular predictor of metabolic type GC and prognostic factor in GC. Copyright © 2013 Elsevier Inc. All rights reserved.

Niche of harmful alga Aureococcus anophagefferens revealed through ecogenomics

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Gobler, C J; Grigoriev, I V; Berry, D L; Dyhrman, S T; Wilhelm, S W; Salamov, A; Lobanov, A V; Zhang, Y; Collier, J L; Wurch, L L; Kustka, A B; Dill, B D; Shah, M; VerBerkomes, N C; Kuo, A; Terry, A; Pangilinan, J; Lindquist, E A; Lucas, S; Paulsen, I; Hattenrath-Lehmann, T K; Talmage, S; Walker, E A; Koch, F; Burson, A M; Marcoval, M A; Tang, Y; LeCleir, G R; Coyne, K J; Berg, G M; Bertrand, E M; Saito, M A; Gladyshev, V N

2011-03-02

Harmful algal blooms (HABs) cause significant economic and ecological damage worldwide. Despite considerable efforts, a comprehensive understanding of the factors that promote these blooms has been lacking because the biochemical pathways that facilitate their dominance relative to other phytoplankton within specific environments have not been identified. Here, biogeochemical measurements demonstrated that the harmful alga Aureococcus anophagefferens outcompeted co-occurring phytoplankton in estuaries with elevated levels of dissolved organic matter and turbidity and low levels of dissolved inorganic nitrogen. We subsequently sequenced the first HAB genome (A. anophagefferens) and compared its gene complement to those of six competing phytoplankton species identified via metaproteomics. Using an ecogenomic approach, we specifically focused on the gene sets that may facilitate dominance within the environmental conditions present during blooms. A. anophagefferens possesses a larger genome (56 mbp) and more genes involved in light harvesting, organic carbon and nitrogen utilization, and encoding selenium- and metal-requiring enzymes than competing phytoplankton. Genes for the synthesis of microbial deterrents likely permit the proliferation of this species with reduced mortality losses during blooms. Collectively, these findings suggest that anthropogenic activities resulting in elevated levels of turbidity, organic matter, and metals have opened a niche within coastal ecosystems that ideally suits the unique genetic capacity of A. anophagefferens and thus has facilitated the proliferation of this and potentially other HABs.

Niche of harmful alga Aureococcus anophagefferens revealed through ecogenomics

Energy Technology Data Exchange (ETDEWEB)

Grigoriev, Igor; Gobler, Christopher; Salamov, Asaf; Kuo, Alan; Terry, Astrid; Pangillian, Jasmyn; Lindquist, Erika; Lucas, Susan; Berry, Dianna; Dyhrman, Sonya; Wilhelm, Steven; Lobanov, Alexei; Zhang, Yan; Collier, Jackie; Wurch, Louie; Kusta, Adam; Dill, Brian; Shsh, Manesh; VerBerkmoes, Nathan; Paulsen, Ian; Hattenrath-Lehmann, Theresa; Talmage, Stephanie; Walker, Elyse; Koch, Florian; Burson, Amanda; Marcoval, Maria; Tang, Yin-Zhong; LeCleir, Gary; Coyne, Kathyrn; Berg, Gry; Bertrand, Erin; Saito, Mak; Gladyshev, Vadim

2011-02-18

Harmful algal blooms (HABs) cause significant economic and ecological damage worldwide. Despite considerable efforts, a comprehensive understanding of the factors that promote these blooms has been lacking, because the biochemical pathways that facilitate their dominance relative to other phytoplankton within specific environments have not been identified. Here, biogeochemical measurements showed that the harmful alga Aureococcus anophagefferens outcompeted co-occurring phytoplankton in estuaries with elevated levels of dissolved organic matter and turbidity and low levels of dissolved inorganic nitrogen. We subsequently sequenced the genome of A. anophagefferens and compared its gene complement with those of six competing phytoplankton species identified through metaproteomics. Using an ecogenomic approach, we specifically focused on gene sets that may facilitate dominance within the environmental conditions present during blooms. A. anophagefferens possesses a larger genome (56 Mbp) and has more genes involved in light harvesting, organic carbon and nitrogen use, and encoding selenium- and metal-requiring enzymes than competing phytoplankton. Genes for the synthesis of microbial deterrents likely permit the proliferation of this species, with reduced mortality losses during blooms. Collectively, these findings suggest that anthropogenic activities resulting in elevated levels of turbidity, organic matter, and metals have opened a niche within coastal ecosystems that ideally suits the unique genetic capacity of A. anophagefferens and thus, has facilitated the proliferation of this and potentially other HABs.

Stem cell niche-specific Ebf3 maintains the bone marrow cavity.

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Seike, Masanari; Omatsu, Yoshiki; Watanabe, Hitomi; Kondoh, Gen; Nagasawa, Takashi

2018-03-01

Bone marrow is the tissue filling the space between bone surfaces. Hematopoietic stem cells (HSCs) are maintained by special microenvironments known as niches within bone marrow cavities. Mesenchymal cells, termed CXC chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells or leptin receptor-positive (LepR + ) cells, are a major cellular component of HSC niches that gives rise to osteoblasts in bone marrow. However, it remains unclear how osteogenesis is prevented in most CAR/LepR + cells to maintain HSC niches and marrow cavities. Here, using lineage tracing, we found that the transcription factor early B-cell factor 3 (Ebf3) is preferentially expressed in CAR/LepR + cells and that Ebf3-expressing cells are self-renewing mesenchymal stem cells in adult marrow. When Ebf3 is deleted in CAR/LepR + cells, HSC niche function is severely impaired, and bone marrow is osteosclerotic with increased bone in aged mice. In mice lacking Ebf1 and Ebf3 , CAR/LepR + cells exhibiting a normal morphology are abundantly present, but their niche function is markedly impaired with depleted HSCs in infant marrow. Subsequently, the mutants become progressively more osteosclerotic, leading to the complete occlusion of marrow cavities in early adulthood. CAR/LepR + cells differentiate into bone-producing cells with reduced HSC niche factor expression in the absence of Ebf1/Ebf3 Thus, HSC cellular niches express Ebf3 that is required to create HSC niches, to inhibit their osteoblast differentiation, and to maintain spaces for HSCs. © 2018 Seike et al.; Published by Cold Spring Harbor Laboratory Press.

An introduction to niche construction theory.

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Laland, Kevin; Matthews, Blake; Feldman, Marcus W

Niche construction refers to the modification of selective environments by organisms. Theoretical and empirical studies of niche construction are increasing in importance as foci in evolutionary ecology. This special edition presents theoretical and empirical research that illustrates the significance of niche construction to the field. Here we set the scene for the following papers by (1) discussing the history of niche construction research, (2) providing clear definitions that distinguish niche construction from related concepts such as ecosystem engineering and the extended phenotype, (3) providing a brief summary of the findings of niche construction research, (4) discussing the contribution of niche construction and ecological inheritance to (a) expanded notions of inheritance, and (b) the extended evolutionary synthesis, and (5) briefly touching on some of the issues that underlie the controversies over niche construction.

Antibiotic Resistant Superbugs: Assessment of the Interrelationship of Occurrence in Clinical Settings and Environmental Niches

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Anthony Ayodeji Adegoke

2016-12-01

Full Text Available The increasing threat to global health posed by antibiotic resistance remains of serious concern. Human health remains at higher risk due to several reported therapeutic failures to many life threatening drug resistant microbial infections. The resultant effects have been prolonged hospital stay, higher cost of alternative therapy, increased mortality, etc. This opinionated review considers the two main concerns in integrated human health risk assessment (i.e., residual antibiotics and antibiotic resistant genes in various compartments of human environment, as well as clinical dynamics associated with the development and transfer of antibiotic resistance (AR. Contributions of quorum sensing, biofilms, enzyme production, and small colony variants in bacteria, among other factors in soil, water, animal farm and clinical settings were also considered. Every potential factor in environmental and clinical settings that brings about AR needs to be identified for the summative effects in overall resistance. There is a need to embrace coordinated multi-locational approaches and interrelationships to track the emergence of resistance in different niches in soil and water versus the hospital environment. The further integration with advocacy, legislation, enforcement, technological innovations and further research input and recourse to WHO guidelines on antibiotic policy would be advantageous towards addressing the emergence of antibiotic resistant superbugs.

Market niche analysis in the casino gaming industry.

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Dandurand, L

1990-03-01

This article discusses the nature of market niche analysis in the casino gaming industry. It presents four approaches for conducting market niche analysis. An an example of one approach, the Las Vegas Visitor Profile Study is used to identify a premium niche in the Las Vegas Slot Target Market. A detailed examination of the premium niche profile provides a description of the typical premium slot player. The description of the typical premium player leads to hypotheses regarding needs (the unique preference set) of the premium player. An analysis of the unique preference set suggests an appropriate enhanced marketing program.

Genomic determinants of sporulation in Bacilli and Clostridia: towards the minimal set of sporulation-specific genes.

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Galperin, Michael Y; Mekhedov, Sergei L; Puigbo, Pere; Smirnov, Sergey; Wolf, Yuri I; Rigden, Daniel J

2012-11-01

Three classes of low-G+C Gram-positive bacteria (Firmicutes), Bacilli, Clostridia and Negativicutes, include numerous members that are capable of producing heat-resistant endospores. Spore-forming firmicutes include many environmentally important organisms, such as insect pathogens and cellulose-degrading industrial strains, as well as human pathogens responsible for such diseases as anthrax, botulism, gas gangrene and tetanus. In the best-studied model organism Bacillus subtilis, sporulation involves over 500 genes, many of which are conserved among other bacilli and clostridia. This work aimed to define the genomic requirements for sporulation through an analysis of the presence of sporulation genes in various firmicutes, including those with smaller genomes than B. subtilis. Cultivable spore-formers were found to have genomes larger than 2300 kb and encompass over 2150 protein-coding genes of which 60 are orthologues of genes that are apparently essential for sporulation in B. subtilis. Clostridial spore-formers lack, among others, spoIIB, sda, spoVID and safA genes and have non-orthologous displacements of spoIIQ and spoIVFA, suggesting substantial differences between bacilli and clostridia in the engulfment and spore coat formation steps. Many B. subtilis sporulation genes, particularly those encoding small acid-soluble spore proteins and spore coat proteins, were found only in the family Bacillaceae, or even in a subset of Bacillus spp. Phylogenetic profiles of sporulation genes, compiled in this work, confirm the presence of a common sporulation gene core, but also illuminate the diversity of the sporulation processes within various lineages. These profiles should help further experimental studies of uncharacterized widespread sporulation genes, which would ultimately allow delineation of the minimal set(s) of sporulation-specific genes in Bacilli and Clostridia. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

Comparative genomic analysis of SET domain family reveals the origin, expansion, and putative function of the arthropod-specific SmydA genes as histone modifiers in insects.

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Jiang, Feng; Liu, Qing; Wang, Yanli; Zhang, Jie; Wang, Huimin; Song, Tianqi; Yang, Meiling; Wang, Xianhui; Kang, Le

2017-06-01

The SET domain is an evolutionarily conserved motif present in histone lysine methyltransferases, which are important in the regulation of chromatin and gene expression in animals. In this study, we searched for SET domain-containing genes (SET genes) in all of the 147 arthropod genomes sequenced at the time of carrying out this experiment to understand the evolutionary history by which SET domains have evolved in insects. Phylogenetic and ancestral state reconstruction analysis revealed an arthropod-specific SET gene family, named SmydA, that is ancestral to arthropod animals and specifically diversified during insect evolution. Considering that pseudogenization is the most probable fate of the new emerging gene copies, we provided experimental and evolutionary evidence to demonstrate their essential functions. Fluorescence in situ hybridization analysis and in vitro methyltransferase activity assays showed that the SmydA-2 gene was transcriptionally active and retained the original histone methylation activity. Expression knockdown by RNA interference significantly increased mortality, implying that the SmydA genes may be essential for insect survival. We further showed predominantly strong purifying selection on the SmydA gene family and a potential association between the regulation of gene expression and insect phenotypic plasticity by transcriptome analysis. Overall, these data suggest that the SmydA gene family retains essential functions that may possibly define novel regulatory pathways in insects. This work provides insights into the roles of lineage-specific domain duplication in insect evolution. © The Authors 2017. Published by Oxford University Press.

The Molecular Signatures Database (MSigDB) hallmark gene set collection.

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Liberzon, Arthur; Birger, Chet; Thorvaldsdóttir, Helga; Ghandi, Mahmoud; Mesirov, Jill P; Tamayo, Pablo

2015-12-23

The Molecular Signatures Database (MSigDB) is one of the most widely used and comprehensive databases of gene sets for performing gene set enrichment analysis. Since its creation, MSigDB has grown beyond its roots in metabolic disease and cancer to include >10,000 gene sets. These better represent a wider range of biological processes and diseases, but the utility of the database is reduced by increased redundancy across, and heterogeneity within, gene sets. To address this challenge, here we use a combination of automated approaches and expert curation to develop a collection of "hallmark" gene sets as part of MSigDB. Each hallmark in this collection consists of a "refined" gene set, derived from multiple "founder" sets, that conveys a specific biological state or process and displays coherent expression. The hallmarks effectively summarize most of the relevant information of the original founder sets and, by reducing both variation and redundancy, provide more refined and concise inputs for gene set enrichment analysis.

Evaluation of endogenous control genes for gene expression studies across multiple tissues and in the specific sets of fat- and muscle-type samples of the pig.

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Gu, Y R; Li, M Z; Zhang, K; Chen, L; Jiang, A A; Wang, J Y; Li, X W

2011-08-01

To normalize a set of quantitative real-time PCR (q-PCR) data, it is essential to determine an optimal number/set of housekeeping genes, as the abundance of housekeeping genes can vary across tissues or cells during different developmental stages, or even under certain environmental conditions. In this study, of the 20 commonly used endogenous control genes, 13, 18 and 17 genes exhibited credible stability in 56 different tissues, 10 types of adipose tissue and five types of muscle tissue, respectively. Our analysis clearly showed that three optimal housekeeping genes are adequate for an accurate normalization, which correlated well with the theoretical optimal number (r ≥ 0.94). In terms of economical and experimental feasibility, we recommend the use of the three most stable housekeeping genes for calculating the normalization factor. Based on our results, the three most stable housekeeping genes in all analysed samples (TOP2B, HSPCB and YWHAZ) are recommended for accurate normalization of q-PCR data. We also suggest that two different sets of housekeeping genes are appropriate for 10 types of adipose tissue (the HSPCB, ALDOA and GAPDH genes) and five types of muscle tissue (the TOP2B, HSPCB and YWHAZ genes), respectively. Our report will serve as a valuable reference for other studies aimed at measuring tissue-specific mRNA abundance in porcine samples. © 2011 Blackwell Verlag GmbH.

A pursuit of lineage-specific and niche-specific proteome features in the world of archaea.

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Roy Chowdhury, Anindya; Dutta, Chitra

2012-06-12

Archaea evoke interest among researchers for two enigmatic characteristics -a combination of bacterial and eukaryotic components in their molecular architectures and an enormous diversity in their life-style and metabolic capabilities. Despite considerable research efforts, lineage- specific/niche-specific molecular features of the whole archaeal world are yet to be fully unveiled. The study offers the first large-scale in silico proteome analysis of all archaeal species of known genome sequences with a special emphasis on methanogenic and sulphur-metabolising archaea. Overall amino acid usage in archaea is dominated by GC-bias. But the environmental factors like oxygen requirement or thermal adaptation seem to play important roles in selection of residues with no GC-bias at the codon level. All methanogens, irrespective of their thermal/salt adaptation, show higher usage of Cys and have relatively acidic proteomes, while the proteomes of sulphur-metabolisers have higher aromaticity and more positive charges. Despite of exhibiting thermophilic life-style, korarchaeota possesses an acidic proteome. Among the distinct trends prevailing in COGs (Cluster of Orthologous Groups of proteins) distribution profiles, crenarchaeal organisms display higher intra-order variations in COGs repertoire, especially in the metabolic ones, as compared to euryarchaea. All methanogens are characterised by a presence of 22 exclusive COGs. Divergences in amino acid usage, aromaticity/charge profiles and COG repertoire among methanogens and sulphur-metabolisers, aerobic and anaerobic archaea or korarchaeota and nanoarchaeota, as elucidated in the present study, point towards the presence of distinct molecular strategies for niche specialization in the archaeal world.

A pursuit of lineage-specific and niche-specific proteome features in the world of archaea

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Roy Chowdhury Anindya

2012-06-01

Full Text Available Abstract Background Archaea evoke interest among researchers for two enigmatic characteristics –a combination of bacterial and eukaryotic components in their molecular architectures and an enormous diversity in their life-style and metabolic capabilities. Despite considerable research efforts, lineage- specific/niche-specific molecular features of the whole archaeal world are yet to be fully unveiled. The study offers the first large-scale in silico proteome analysis of all archaeal species of known genome sequences with a special emphasis on methanogenic and sulphur-metabolising archaea. Results Overall amino acid usage in archaea is dominated by GC-bias. But the environmental factors like oxygen requirement or thermal adaptation seem to play important roles in selection of residues with no GC-bias at the codon level. All methanogens, irrespective of their thermal/salt adaptation, show higher usage of Cys and have relatively acidic proteomes, while the proteomes of sulphur-metabolisers have higher aromaticity and more positive charges. Despite of exhibiting thermophilic life-style, korarchaeota possesses an acidic proteome. Among the distinct trends prevailing in COGs (Cluster of Orthologous Groups of proteins distribution profiles, crenarchaeal organisms display higher intra-order variations in COGs repertoire, especially in the metabolic ones, as compared to euryarchaea. All methanogens are characterised by a presence of 22 exclusive COGs. Conclusions Divergences in amino acid usage, aromaticity/charge profiles and COG repertoire among methanogens and sulphur-metabolisers, aerobic and anaerobic archaea or korarchaeota and nanoarchaeota, as elucidated in the present study, point towards the presence of distinct molecular strategies for niche specialization in the archaeal world.

Combgap Promotes Ovarian Niche Development and Chromatin Association of EcR-Binding Regions in BR-C.

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Hitrik, Anna; Popliker, Malka; Gancz, Dana; Mukamel, Zohar; Lifshitz, Aviezer; Schwartzman, Omer; Tanay, Amos; Gilboa, Lilach

2016-11-01

The development of niches for tissue-specific stem cells is an important aspect of stem cell biology. Determination of niche size and niche numbers during organogenesis involves precise control of gene expression. How this is achieved in the context of a complex chromatin landscape is largely unknown. Here we show that the nuclear protein Combgap (Cg) supports correct ovarian niche formation in Drosophila by controlling ecdysone-Receptor (EcR)- mediated transcription and long-range chromatin contacts in the broad locus (BR-C). Both cg and BR-C promote ovarian growth and the development of niches for germ line stem cells. BR-C levels were lower when Combgap was either reduced or over-expressed, indicating an intricate regulation of the BR-C locus by Combgap. Polytene chromosome stains showed that Cg co-localizes with EcR, the major regulator of BR-C, at the BR-C locus and that EcR binding to chromatin was sensitive to changes in Cg levels. Proximity ligation assay indicated that the two proteins could reside in the same complex. Finally, chromatin conformation analysis revealed that EcR-bound regions within BR-C, which span ~30 KBs, contacted each other. Significantly, these contacts were stabilized in an ecdysone- and Combgap-dependent manner. Together, these results highlight Combgap as a novel regulator of chromatin structure that promotes transcription of ecdysone target genes and ovarian niche formation.

A novel CpG island set identifies tissue-specific methylation at developmental gene loci.

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Robert Illingworth

2008-01-01

Full Text Available CpG islands (CGIs are dense clusters of CpG sequences that punctuate the CpG-deficient human genome and associate with many gene promoters. As CGIs also differ from bulk chromosomal DNA by their frequent lack of cytosine methylation, we devised a CGI enrichment method based on nonmethylated CpG affinity chromatography. The resulting library was sequenced to define a novel human blood CGI set that includes many that are not detected by current algorithms. Approximately half of CGIs were associated with annotated gene transcription start sites, the remainder being intra- or intergenic. Using an array representing over 17,000 CGIs, we established that 6%-8% of CGIs are methylated in genomic DNA of human blood, brain, muscle, and spleen. Inter- and intragenic CGIs are preferentially susceptible to methylation. CGIs showing tissue-specific methylation were overrepresented at numerous genetic loci that are essential for development, including HOX and PAX family members. The findings enable a comprehensive analysis of the roles played by CGI methylation in normal and diseased human tissues.

Single-cell analyses identify bioengineered niches for enhanced maintenance of hematopoietic stem cells.

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Roch, Aline; Giger, Sonja; Girotra, Mukul; Campos, Vasco; Vannini, Nicola; Naveiras, Olaia; Gobaa, Samy; Lutolf, Matthias P

2017-08-09

The in vitro expansion of long-term hematopoietic stem cells (HSCs) remains a substantial challenge, largely because of our limited understanding of the mechanisms that control HSC fate choices. Using single-cell multigene expression analysis and time-lapse microscopy, here we define gene expression signatures and cell cycle hallmarks of murine HSCs and the earliest multipotent progenitors (MPPs), and analyze systematically single HSC fate choices in culture. Our analysis revealed twelve differentially expressed genes marking the quiescent HSC state, including four genes encoding cell-cell interaction signals in the niche. Under basal culture conditions, most HSCs rapidly commit to become early MPPs. In contrast, when we present ligands of the identified niche components such as JamC or Esam within artificial niches, HSC cycling is reduced and long-term multipotency in vivo is maintained. Our approach to bioengineer artificial niches should be useful in other stem cell systems.Haematopoietic stem cell (HSC) self-renewal is not sufficiently understood to recapitulate in vitro. Here, the authors generate gene signature and cell cycle hallmarks of single murine HSCs, and use identified endothelial receptors Esam and JamC as substrates to enhance HSC growth in engineered niches.

Modulating the stem cell niche for tissue regeneration

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Lane, Steven W; Williams, David A; Watt, Fiona M

2015-01-01

The field of regenerative medicine holds considerable promise for treating diseases that are currently intractable. Although many researchers are adopting the strategy of cell transplantation for tissue repair, an alternative approach to therapy is to manipulate the stem cell microenvironment, or niche, to facilitate repair by endogenous stem cells. The niche is highly dynamic, with multiple opportunities for intervention. These include administration of small molecules, biologics or biomaterials that target specific aspects of the niche, such as cell-cell and cell–extracellular matrix interactions, to stimulate expansion or differentiation of stem cells, or to cause reversion of differentiated cells to stem cells. Nevertheless, there are several challenges in targeting the niche therapeutically, not least that of achieving specificity of delivery and responses. We envisage that successful treatments in regenerative medicine will involve different combinations of factors to target stem cells and niche cells, applied at different times to effect recovery according to the dynamics of stem cell–niche interactions. PMID:25093887

A Unique Set of the Burkholderia Collagen-Like Proteins Provides Insight into Pathogenesis, Genome Evolution and Niche Adaptation, and Infection Detection.

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Bachert, Beth A; Choi, Soo J; Snyder, Anna K; Rio, Rita V M; Durney, Brandon C; Holland, Lisa A; Amemiya, Kei; Welkos, Susan L; Bozue, Joel A; Cote, Christopher K; Berisio, Rita; Lukomski, Slawomir

2015-01-01

Burkholderia pseudomallei and Burkholderia mallei, classified as category B priority pathogens, are significant human and animal pathogens that are highly infectious and broad-spectrum antibiotic resistant. Currently, the pathogenicity mechanisms utilized by Burkholderia are not fully understood, and correct diagnosis of B. pseudomallei and B. mallei infection remains a challenge due to limited detection methods. Here, we provide a comprehensive analysis of a set of 13 novel Burkholderia collagen-like proteins (Bucl) that were identified among B. pseudomallei and B. mallei select agents. We infer that several Bucl proteins participate in pathogenesis based on their noncollagenous domains that are associated with the components of a type III secretion apparatus and membrane transport systems. Homology modeling of the outer membrane efflux domain of Bucl8 points to a role in multi-drug resistance. We determined that bucl genes are widespread in B. pseudomallei and B. mallei; Fischer's exact test and Cramer's V2 values indicate that the majority of bucl genes are highly associated with these pathogenic species versus nonpathogenic B. thailandensis. We designed a bucl-based quantitative PCR assay which was able to detect B. pseudomallei infection in a mouse with a detection limit of 50 CFU. Finally, chromosomal mapping and phylogenetic analysis of bucl loci revealed considerable genomic plasticity and adaptation of Burkholderia spp. to host and environmental niches. In this study, we identified a large set of phylogenetically unrelated bucl genes commonly found in Burkholderia select agents, encoding predicted pathogenicity factors, detection targets, and vaccine candidates.

Introducing MERGANSER: A Flexible Framework for Ecological Niche Modeling

Science.gov (United States)

Klawonn, M.; Dow, E. M.

2015-12-01

Ecological Niche Modeling (ENM) is a collection of techniques to find a "fundamental niche", the range of environmental conditions suitable for a species' survival in the absence of inter-species interactions, given a set of environmental parameters. Traditional approaches to ENM face a number of obstacles including limited data accessibility, data management problems, computational costs, interface usability, and model validation. The MERGANSER system, which stands for Modeling Ecological Residency Given A Normalized Set of Environmental Records, addresses these issues through powerful data persistence and flexible data access, coupled with a clear presentation of results and fine-tuned control over model parameters. MERGANSER leverages data measuring 72 weather related phenomena, land cover, soil type, population, species occurrence, general species information, and elevation, totaling over 1.5 TB of data. To the best of the authors' knowledge, MERGANSER uses higher-resolution spatial data sets than previously published models. Since MERGANSER stores data in an instance of Apache SOLR, layers generated in support of niche models are accessible to users via simplified Apache Lucene queries. This is made even simpler via an HTTP front end that generates Lucene queries automatically. Specifically, a user need only enter the name of a place and a species to run a model. Using this approach to synthesizing model layers, the MERGANSER system has successfully reproduced previously published niche model results with a simplified user experience. Input layers for the model are generated dynamically using OpenStreetMap and SOLR's spatial search functionality. Models are then run using either user-specified or automatically determined parameters after normalizing them into a common grid. Finally, results are visualized in the web interface, which allows for quick validation. Model results and all surrounding metadata are also accessible to the user for further study.

Gene set analysis of the EADGENE chicken data-set

DEFF Research Database (Denmark)

Skarman, Axel; Jiang, Li; Hornshøj, Henrik

2009-01-01

 Abstract Background: Gene set analysis is considered to be a way of improving our biological interpretation of the observed expression patterns. This paper describes different methods applied to analyse expression data from a chicken DNA microarray dataset. Results: Applying different gene set...... analyses to the chicken expression data led to different ranking of the Gene Ontology terms tested. A method for prediction of possible annotations was applied. Conclusion: Biological interpretation based on gene set analyses dependent on the statistical method used. Methods for predicting the possible...

Time-Course Gene Set Analysis for Longitudinal Gene Expression Data.

Directory of Open Access Journals (Sweden)

Boris P Hejblum

2015-06-01

Full Text Available Gene set analysis methods, which consider predefined groups of genes in the analysis of genomic data, have been successfully applied for analyzing gene expression data in cross-sectional studies. The time-course gene set analysis (TcGSA introduced here is an extension of gene set analysis to longitudinal data. The proposed method relies on random effects modeling with maximum likelihood estimates. It allows to use all available repeated measurements while dealing with unbalanced data due to missing at random (MAR measurements. TcGSA is a hypothesis driven method that identifies a priori defined gene sets with significant expression variations over time, taking into account the potential heterogeneity of expression within gene sets. When biological conditions are compared, the method indicates if the time patterns of gene sets significantly differ according to these conditions. The interest of the method is illustrated by its application to two real life datasets: an HIV therapeutic vaccine trial (DALIA-1 trial, and data from a recent study on influenza and pneumococcal vaccines. In the DALIA-1 trial TcGSA revealed a significant change in gene expression over time within 69 gene sets during vaccination, while a standard univariate individual gene analysis corrected for multiple testing as well as a standard a Gene Set Enrichment Analysis (GSEA for time series both failed to detect any significant pattern change over time. When applied to the second illustrative data set, TcGSA allowed the identification of 4 gene sets finally found to be linked with the influenza vaccine too although they were found to be associated to the pneumococcal vaccine only in previous analyses. In our simulation study TcGSA exhibits good statistical properties, and an increased power compared to other approaches for analyzing time-course expression patterns of gene sets. The method is made available for the community through an R package.

The crosstalk between hematopoietic stem cells and their niches.

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Durand, Charles; Charbord, Pierre; Jaffredo, Thierry

2018-07-01

Hematopoietic stem cells (HSCs) reside in specific microenvironments also called niches that regulate HSC functions. Understanding the molecular and cellular mechanisms involved in the crosstalk between HSCs and niche cells is a major issue in stem cell biology and regenerative medicine. The purpose of this review is to discuss recent advances in this field with particular emphasis on the transcriptional landscape of HSC niche cells and the roles of extracellular vesicles (EVs) in the dialog between HSCs and their microenvironments. The development of high-throughput technologies combined with computational methods has considerably improved our knowledge on the molecular identity of HSC niche cells. Accumulating evidence strongly suggest that the dialog between HSCs and their niches is bidirectional and that EVs play an important role in this process. These advances bring a unique conceptual and methodological framework for understanding the molecular complexity of the HSC niche and identifying novel HSC regulators. They are also promising for exploring the reciprocal influence of HSCs on niche cells and delivering specific molecules to HSCs in regenerative medicine.

Gene set analysis using variance component tests.

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Huang, Yen-Tsung; Lin, Xihong

2013-06-28

Gene set analyses have become increasingly important in genomic research, as many complex diseases are contributed jointly by alterations of numerous genes. Genes often coordinate together as a functional repertoire, e.g., a biological pathway/network and are highly correlated. However, most of the existing gene set analysis methods do not fully account for the correlation among the genes. Here we propose to tackle this important feature of a gene set to improve statistical power in gene set analyses. We propose to model the effects of an independent variable, e.g., exposure/biological status (yes/no), on multiple gene expression values in a gene set using a multivariate linear regression model, where the correlation among the genes is explicitly modeled using a working covariance matrix. We develop TEGS (Test for the Effect of a Gene Set), a variance component test for the gene set effects by assuming a common distribution for regression coefficients in multivariate linear regression models, and calculate the p-values using permutation and a scaled chi-square approximation. We show using simulations that type I error is protected under different choices of working covariance matrices and power is improved as the working covariance approaches the true covariance. The global test is a special case of TEGS when correlation among genes in a gene set is ignored. Using both simulation data and a published diabetes dataset, we show that our test outperforms the commonly used approaches, the global test and gene set enrichment analysis (GSEA). We develop a gene set analyses method (TEGS) under the multivariate regression framework, which directly models the interdependence of the expression values in a gene set using a working covariance. TEGS outperforms two widely used methods, GSEA and global test in both simulation and a diabetes microarray data.

Individual and species-specific traits explain niche size and functional role in spiders as generalist predators.

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Sanders, Dirk; Vogel, Esther; Knop, Eva

2015-01-01

The function of a predator within a community is greatly based on its trophic niche, that is the number and the strength of feeding links. In generalist predators, which feed on a wide range of prey, the size and position of the trophic niche is likely determined by traits such as hunting mode, the stratum they occur in, their body size and age. We used stable isotope analyses ((13)C and (15)N) to measure the trophic niche size of nine spider species within a forest hedge community and tested for species traits and individual traits that influence stable isotope enrichment, niche size and resource use. The spiders Enoplognatha, Philodromus, Floronia, and Heliophanus had large isotopic niches, which correspond to a more generalistic feeding behaviour. In contrast, Araneus, Metellina and Agelena, as top predators in the system, had rather narrow niches. We found a negative correlation between trophic position and niche size. Differences in trophic position in spiders were explained by body size, hunting modes and stratum, while niche size was influenced by hunting mode. In Philodromus, the size of the trophic niche increased significantly with age. Fitting spiders to functional groups according to their mean body size, hunting mode and their habitat domain resulted in largely separated niches, which indicates that these traits are meaningful for separating functional entities in spiders. Functional groups based on habitat domain (stratum) caught the essential functional differences between the species with species higher up in the vegetation feeding on flying insects and herb and ground species also preying on forest floor decomposers. Interestingly, we found a gradient from large species using a higher habitat domain and having a smaller niche to smaller species foraging closer to the ground and having a larger niche. This shows that even within generalist predators, such as spiders, there is a gradient of specialism that can be predicted by functional traits. �

Functional traits, convergent evolution, and periodic tables of niches.

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Winemiller, Kirk O; Fitzgerald, Daniel B; Bower, Luke M; Pianka, Eric R

2015-08-01

Ecology is often said to lack general theories sufficiently predictive for applications. Here, we examine the concept of a periodic table of niches and feasibility of niche classification schemes from functional trait and performance data. Niche differences and their influence on ecological patterns and processes could be revealed effectively by first performing data reduction/ordination analyses separately on matrices of trait and performance data compiled according to logical associations with five basic niche 'dimensions', or aspects: habitat, life history, trophic, defence and metabolic. Resultant patterns then are integrated to produce interpretable niche gradients, ordinations and classifications. Degree of scheme periodicity would depend on degrees of niche conservatism and convergence causing species clustering across multiple niche dimensions. We analysed a sample data set containing trait and performance data to contrast two approaches for producing niche schemes: species ordination within niche gradient space, and niche categorisation according to trait-value thresholds. Creation of niche schemes useful for advancing ecological knowledge and its applications will depend on research that produces functional trait and performance datasets directly related to niche dimensions along with criteria for data standardisation and quality. As larger databases are compiled, opportunities will emerge to explore new methods for data reduction, ordination and classification. © 2015 The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.

Evolution of climatic niche specialization: a phylogenetic analysis in amphibians.

Science.gov (United States)

Bonetti, Maria Fernanda; Wiens, John J

2014-11-22

The evolution of climatic niche specialization has important implications for many topics in ecology, evolution and conservation. The climatic niche reflects the set of temperature and precipitation conditions where a species can occur. Thus, specialization to a limited set of climatic conditions can be important for understanding patterns of biogeography, species richness, community structure, allopatric speciation, spread of invasive species and responses to climate change. Nevertheless, the factors that determine climatic niche width (level of specialization) remain poorly explored. Here, we test whether species that occur in more extreme climates are more highly specialized for those conditions, and whether there are trade-offs between niche widths on different climatic niche axes (e.g. do species that tolerate a broad range of temperatures tolerate only a limited range of precipitation regimes?). We test these hypotheses in amphibians, using phylogenetic comparative methods and global-scale datasets, including 2712 species with both climatic and phylogenetic data. Our results do not support either hypothesis. Rather than finding narrower niches in more extreme environments, niches tend to be narrower on one end of a climatic gradient but wider on the other. We also find that temperature and precipitation niche breadths are positively related, rather than showing trade-offs. Finally, our results suggest that most amphibian species occur in relatively warm and dry environments and have relatively narrow climatic niche widths on both of these axes. Thus, they may be especially imperilled by anthropogenic climate change. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Genus-Wide Comparative Genomics of Malassezia Delineates Its Phylogeny, Physiology, and Niche Adaptation on Human Skin.

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Wu, Guangxi; Zhao, He; Li, Chenhao; Rajapakse, Menaka Priyadarsani; Wong, Wing Cheong; Xu, Jun; Saunders, Charles W; Reeder, Nancy L; Reilman, Raymond A; Scheynius, Annika; Sun, Sheng; Billmyre, Blake Robert; Li, Wenjun; Averette, Anna Floyd; Mieczkowski, Piotr; Heitman, Joseph; Theelen, Bart; Schröder, Markus S; De Sessions, Paola Florez; Butler, Geraldine; Maurer-Stroh, Sebastian; Boekhout, Teun; Nagarajan, Niranjan; Dawson, Thomas L

2015-11-01

Malassezia is a unique lipophilic genus in class Malasseziomycetes in Ustilaginomycotina, (Basidiomycota, fungi) that otherwise consists almost exclusively of plant pathogens. Malassezia are typically isolated from warm-blooded animals, are dominant members of the human skin mycobiome and are associated with common skin disorders. To characterize the genetic basis of the unique phenotypes of Malassezia spp., we sequenced the genomes of all 14 accepted species and used comparative genomics against a broad panel of fungal genomes to comprehensively identify distinct features that define the Malassezia gene repertoire: gene gain and loss; selection signatures; and lineage-specific gene family expansions. Our analysis revealed key gene gain events (64) with a single gene conserved across all Malassezia but absent in all other sequenced Basidiomycota. These likely horizontally transferred genes provide intriguing gain-of-function events and prime candidates to explain the emergence of Malassezia. A larger set of genes (741) were lost, with enrichment for glycosyl hydrolases and carbohydrate metabolism, concordant with adaptation to skin's carbohydrate-deficient environment. Gene family analysis revealed extensive turnover and underlined the importance of secretory lipases, phospholipases, aspartyl proteases, and other peptidases. Combining genomic analysis with a re-evaluation of culture characteristics, we establish the likely lipid-dependence of all Malassezia. Our phylogenetic analysis sheds new light on the relationship between Malassezia and other members of Ustilaginomycotina, as well as phylogenetic lineages within the genus. Overall, our study provides a unique genomic resource for understanding Malassezia niche-specificity and potential virulence, as well as their abundance and distribution in the environment and on human skin.

Genus-Wide Comparative Genomics of Malassezia Delineates Its Phylogeny, Physiology, and Niche Adaptation on Human Skin.

Directory of Open Access Journals (Sweden)

Guangxi Wu

2015-11-01

Full Text Available Malassezia is a unique lipophilic genus in class Malasseziomycetes in Ustilaginomycotina, (Basidiomycota, fungi that otherwise consists almost exclusively of plant pathogens. Malassezia are typically isolated from warm-blooded animals, are dominant members of the human skin mycobiome and are associated with common skin disorders. To characterize the genetic basis of the unique phenotypes of Malassezia spp., we sequenced the genomes of all 14 accepted species and used comparative genomics against a broad panel of fungal genomes to comprehensively identify distinct features that define the Malassezia gene repertoire: gene gain and loss; selection signatures; and lineage-specific gene family expansions. Our analysis revealed key gene gain events (64 with a single gene conserved across all Malassezia but absent in all other sequenced Basidiomycota. These likely horizontally transferred genes provide intriguing gain-of-function events and prime candidates to explain the emergence of Malassezia. A larger set of genes (741 were lost, with enrichment for glycosyl hydrolases and carbohydrate metabolism, concordant with adaptation to skin's carbohydrate-deficient environment. Gene family analysis revealed extensive turnover and underlined the importance of secretory lipases, phospholipases, aspartyl proteases, and other peptidases. Combining genomic analysis with a re-evaluation of culture characteristics, we establish the likely lipid-dependence of all Malassezia. Our phylogenetic analysis sheds new light on the relationship between Malassezia and other members of Ustilaginomycotina, as well as phylogenetic lineages within the genus. Overall, our study provides a unique genomic resource for understanding Malassezia niche-specificity and potential virulence, as well as their abundance and distribution in the environment and on human skin.

Plant stem cell niches.

Science.gov (United States)

Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

2012-01-01

Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

Gene specific actions of thyroid hormone receptor subtypes.

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Jean Z Lin

Full Text Available There are two homologous thyroid hormone (TH receptors (TRs α and β, which are members of the nuclear hormone receptor (NR family. While TRs regulate different processes in vivo and other highly related NRs regulate distinct gene sets, initial studies of TR action revealed near complete overlaps in their actions at the level of individual genes. Here, we assessed the extent that TRα and TRβ differ in target gene regulation by comparing effects of equal levels of stably expressed exogenous TRs +/- T(3 in two cell backgrounds (HepG2 and HeLa. We find that hundreds of genes respond to T(3 or to unliganded TRs in both cell types, but were not able to detect verifiable examples of completely TR subtype-specific gene regulation. TR actions are, however, far from identical and we detect TR subtype-specific effects on global T(3 response kinetics in HepG2 cells and many examples of TR subtype specificity at the level of individual genes, including effects on magnitude of response to TR +/- T(3, TR regulation patterns and T(3 dose response. Cycloheximide (CHX treatment confirms that at least some differential effects involve verifiable direct TR target genes. TR subtype/gene-specific effects emerge in the context of widespread variation in target gene response and we suggest that gene-selective effects on mechanism of TR action highlight differences in TR subtype function that emerge in the environment of specific genes. We propose that differential TR actions could influence physiologic and pharmacologic responses to THs and selective TR modulators (STRMs.

Principles for the organization of gene-sets.

Science.gov (United States)

Li, Wentian; Freudenberg, Jan; Oswald, Michaela

2015-12-01

A gene-set, an important concept in microarray expression analysis and systems biology, is a collection of genes and/or their products (i.e. proteins) that have some features in common. There are many different ways to construct gene-sets, but a systematic organization of these ways is lacking. Gene-sets are mainly organized ad hoc in current public-domain databases, with group header names often determined by practical reasons (such as the types of technology in obtaining the gene-sets or a balanced number of gene-sets under a header). Here we aim at providing a gene-set organization principle according to the level at which genes are connected: homology, physical map proximity, chemical interaction, biological, and phenotypic-medical levels. We also distinguish two types of connections between genes: actual connection versus sharing of a label. Actual connections denote direct biological interactions, whereas shared label connection denotes shared membership in a group. Some extensions of the framework are also addressed such as overlapping of gene-sets, modules, and the incorporation of other non-protein-coding entities such as microRNAs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genome-wide survey and developmental expression mapping of zebrafish SET domain-containing genes.

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Xiao-Jian Sun

Full Text Available SET domain-containing proteins represent an evolutionarily conserved family of epigenetic regulators, which are responsible for most histone lysine methylation. Since some of these genes have been revealed to be essential for embryonic development, we propose that the zebrafish, a vertebrate model organism possessing many advantages for developmental studies, can be utilized to study the biological functions of these genes and the related epigenetic mechanisms during early development. To this end, we have performed a genome-wide survey of zebrafish SET domain genes. 58 genes total have been identified. Although gene duplication events give rise to several lineage-specific paralogs, clear reciprocal orthologous relationship reveals high conservation between zebrafish and human SET domain genes. These data were further subject to an evolutionary analysis ranging from yeast to human, leading to the identification of putative clusters of orthologous groups (COGs of this gene family. By means of whole-mount mRNA in situ hybridization strategy, we have also carried out a developmental expression mapping of these genes. A group of maternal SET domain genes, which are implicated in the programming of histone modification states in early development, have been identified and predicted to be responsible for all known sites of SET domain-mediated histone methylation. Furthermore, some genes show specific expression patterns in certain tissues at certain stages, suggesting the involvement of epigenetic mechanisms in the development of these systems. These results provide a global view of zebrafish SET domain histone methyltransferases in evolutionary and developmental dimensions and pave the way for using zebrafish to systematically study the roles of these genes during development.

Niche entrepreneurs in urban systems integration : On the role of individuals in niche formation

NARCIS (Netherlands)

Pesch, U.; Vernay, A.L.; van Bueren, E.M.; Pandis Iveroth, S

2017-01-01

In many sustainable urban innovation projects, the efforts, endurance and enthusiasm of individuals at key positions are considered a crucial factor for success. This article studies the role of individual agency in sociotechnical niches by using Kingdon’s agenda-setting model. Although strategic

THE GERMLINE STEM CELL NICHE UNIT IN MAMMALIAN TESTES

Science.gov (United States)

Oatley, Jon M.; Brinster, Ralph L.

2014-01-01

This review addresses current understanding of the germline stem cell niche unit in mammalian testes. Spermatogenesis is a classic model of tissue-specific stem cell function relying on self-renewal and differentiation of spermatogonial stem cells (SSCs). These fate decisions are influenced by a niche microenvironment composed of a growth factor milieu that is provided by several testis somatic support cell populations. Investigations over the last two decades have identified key determinants of the SSC niche including cytokines that regulate SSC functions and support cells providing these factors, adhesion molecules that influence SSC homing, and developmental heterogeneity of the niche during postnatal aging. Emerging evidence suggests that Sertoli cells are a key support cell population influencing the formation and function of niches by secreting soluble factors and possibly orchestrating contributions of other support cells. Investigations with mice have shown that niche influence on SSC proliferation differs during early postnatal development and adulthood. Moreover, there is mounting evidence of an age-related decline in niche function, which is likely influenced by systemic factors. Defining the attributes of stem cell niches is key to developing methods to utilize these cells for regenerative medicine. The SSC population and associated niche comprise a valuable model system for study that provides fundamental knowledge about the biology of tissue-specific stem cells and their capacity to sustain homeostasis of regenerating tissue lineages. While the stem cell is essential for maintenance of all self-renewing tissues and has received considerable attention, the role of niche cells is at least as important and may prove to be more receptive to modification in regenerative medicine. PMID:22535892

TiGER: a database for tissue-specific gene expression and regulation.

Science.gov (United States)

Liu, Xiong; Yu, Xueping; Zack, Donald J; Zhu, Heng; Qian, Jiang

2008-06-09

Understanding how genes are expressed and regulated in different tissues is a fundamental and challenging question. However, most of currently available biological databases do not focus on tissue-specific gene regulation. The recent development of computational methods for tissue-specific combinational gene regulation, based on transcription factor binding sites, enables us to perform a large-scale analysis of tissue-specific gene regulation in human tissues. The results are stored in a web database called TiGER (Tissue-specific Gene Expression and Regulation). The database contains three types of data including tissue-specific gene expression profiles, combinatorial gene regulations, and cis-regulatory module (CRM) detections. At present the database contains expression profiles for 19,526 UniGene genes, combinatorial regulations for 7,341 transcription factor pairs and 6,232 putative CRMs for 2,130 RefSeq genes. We have developed and made publicly available a database, TiGER, which summarizes and provides large scale data sets for tissue-specific gene expression and regulation in a variety of human tissues. This resource is available at 1.

TiGER: A database for tissue-specific gene expression and regulation

Directory of Open Access Journals (Sweden)

Zack Donald J

2008-06-01

Full Text Available Abstract Background Understanding how genes are expressed and regulated in different tissues is a fundamental and challenging question. However, most of currently available biological databases do not focus on tissue-specific gene regulation. Results The recent development of computational methods for tissue-specific combinational gene regulation, based on transcription factor binding sites, enables us to perform a large-scale analysis of tissue-specific gene regulation in human tissues. The results are stored in a web database called TiGER (Tissue-specific Gene Expression and Regulation. The database contains three types of data including tissue-specific gene expression profiles, combinatorial gene regulations, and cis-regulatory module (CRM detections. At present the database contains expression profiles for 19,526 UniGene genes, combinatorial regulations for 7,341 transcription factor pairs and 6,232 putative CRMs for 2,130 RefSeq genes. Conclusion We have developed and made publicly available a database, TiGER, which summarizes and provides large scale data sets for tissue-specific gene expression and regulation in a variety of human tissues. This resource is available at 1.

Segmentation of electric energy customers by specific niches; Segmentacao de clientes de energia eletrica por nichos especiais

Energy Technology Data Exchange (ETDEWEB)

Silva, Ana Lucia Rodrigues da; Jannuzzi, Gilberto de Martino [Universidade Estadual de Campinas (UNICAMP), SP (Brazil)], E-mail: jannuzzi@fen.unicamp.br

2009-04-15

The article presents the classic segmentation used in electric energy industry for large customers. The paper argues the limitations of this classification, as well as, the potentialities to classify customers for specific niches, the example of that already occurs in other competitive sectors of the economy. Twelve potential forms for classifying large customers in electricity industry are presented: geographic localization; value of the invoice; sector of productive activity; types of share holding composition and enterprise management; forms and characteristics of the use of the electric energy in the final units; degree of technological sophistication; client relation cost benefit; common factors in energy process of purchase; brand associated with the customer; extraordinary factors, such as, urgency, application and volume of energy; personal characteristics of the purchaser in charge of the operation; former-customers who moved from the captive market to the free market and vice versa. The article concludes proposing a new methodology to identify the specific niches of customers in the electric sector, as well as the inductive and restrictive factors of this methodology. (author)

Effect of the absolute statistic on gene-sampling gene-set analysis methods.

Science.gov (United States)

Nam, Dougu

2017-06-01

Gene-set enrichment analysis and its modified versions have commonly been used for identifying altered functions or pathways in disease from microarray data. In particular, the simple gene-sampling gene-set analysis methods have been heavily used for datasets with only a few sample replicates. The biggest problem with this approach is the highly inflated false-positive rate. In this paper, the effect of absolute gene statistic on gene-sampling gene-set analysis methods is systematically investigated. Thus far, the absolute gene statistic has merely been regarded as a supplementary method for capturing the bidirectional changes in each gene set. Here, it is shown that incorporating the absolute gene statistic in gene-sampling gene-set analysis substantially reduces the false-positive rate and improves the overall discriminatory ability. Its effect was investigated by power, false-positive rate, and receiver operating curve for a number of simulated and real datasets. The performances of gene-set analysis methods in one-tailed (genome-wide association study) and two-tailed (gene expression data) tests were also compared and discussed.

Niche Marketing Potentials for Farm Entrepreneurs in Nigeria https ...

African Journals Online (AJOL)

User

. Niche marketing involves targetting a product or service to a small but specific well ... Table 1: Examples of possible niche markets for entrepreneurs in Nigeria. Farm Business .... Concepts, Principles and Decisions, 2nd Edition. Afritowers ...

MAGMA: generalized gene-set analysis of GWAS data.

Science.gov (United States)

de Leeuw, Christiaan A; Mooij, Joris M; Heskes, Tom; Posthuma, Danielle

2015-04-01

By aggregating data for complex traits in a biologically meaningful way, gene and gene-set analysis constitute a valuable addition to single-marker analysis. However, although various methods for gene and gene-set analysis currently exist, they generally suffer from a number of issues. Statistical power for most methods is strongly affected by linkage disequilibrium between markers, multi-marker associations are often hard to detect, and the reliance on permutation to compute p-values tends to make the analysis computationally very expensive. To address these issues we have developed MAGMA, a novel tool for gene and gene-set analysis. The gene analysis is based on a multiple regression model, to provide better statistical performance. The gene-set analysis is built as a separate layer around the gene analysis for additional flexibility. This gene-set analysis also uses a regression structure to allow generalization to analysis of continuous properties of genes and simultaneous analysis of multiple gene sets and other gene properties. Simulations and an analysis of Crohn's Disease data are used to evaluate the performance of MAGMA and to compare it to a number of other gene and gene-set analysis tools. The results show that MAGMA has significantly more power than other tools for both the gene and the gene-set analysis, identifying more genes and gene sets associated with Crohn's Disease while maintaining a correct type 1 error rate. Moreover, the MAGMA analysis of the Crohn's Disease data was found to be considerably faster as well.

Comparing the Healthy Nose and Nasopharynx Microbiota Reveals Continuity As Well As Niche-Specificity

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Ilke De Boeck

2017-11-01

Full Text Available To improve our understanding of upper respiratory tract (URT diseases and the underlying microbial pathogenesis, a better characterization of the healthy URT microbiome is crucial. In this first large-scale study, we obtained more insight in the URT microbiome of healthy adults. Hereto, we collected paired nasal and nasopharyngeal swabs from 100 healthy participants in a citizen-science project. High-throughput 16S rRNA gene V4 amplicon sequencing was performed and samples were processed using the Divisive Amplicon Denoising Algorithm 2 (DADA2 algorithm. This allowed us to identify the bacterial richness and diversity of the samples in terms of amplicon sequence variants (ASVs, with special attention to intragenus variation. We found both niches to have a low overall species richness and uneven distribution. Moreover, based on hierarchical clustering, nasopharyngeal samples could be grouped into some bacterial community types at genus level, of which four were supported to some extent by prediction strength evaluation: one intermixed type with a higher bacterial diversity where Staphylococcus, Corynebacterium, and Dolosigranulum appeared main bacterial members in different relative abundances, and three types dominated by either Moraxella, Streptococcus, or Fusobacterium. Some of these bacterial community types such as Streptococcus and Fusobacterium were nasopharynx-specific and never occurred in the nose. No clear association between the nasopharyngeal bacterial profiles at genus level and the variables age, gender, blood type, season of sampling, or common respiratory allergies was found in this study population, except for smoking showing a positive association with Corynebacterium and Staphylococcus. Based on the fine-scale resolution of the ASVs, both known commensal and potential pathogenic bacteria were found within several genera – particularly in Streptococcus and Moraxella – in our healthy study population. Of interest, the

Species-specific ecological niche modelling predicts different range contractions for Lutzomyia intermedia and a related vector of Leishmania braziliensis following climate change in South America.

Science.gov (United States)

McIntyre, Shannon; Rangel, Elizabeth F; Ready, Paul D; Carvalho, Bruno M

2017-03-24

Before 1996 the phlebotomine sand fly Lutzomyia neivai was usually treated as a synonym of the morphologically similar Lutzomyia intermedia, which has long been considered a vector of Leishmania braziliensis, the causative agent of much cutaneous leishmaniasis in South America. This report investigates the likely range changes of both sand fly species in response to a stabilisation climate change scenario (RCP4.5) and a high greenhouse gas emissions one (RCP8.5). Ecological niche modelling was used to identify areas of South America with climates currently suitable for each species, and then the future distributions of these climates were predicted based on climate change scenarios. Compared with the previous ecological niche model of L. intermedia (sensu lato) produced using the GARP algorithm in 2003, the current investigation modelled the two species separately, making use of verified presence records and additional records after 2001. Also, the new ensemble approach employed ecological niche modelling algorithms (including Maximum Entropy, Random Forests and Support Vector Machines) that have been widely adopted since 2003 and perform better than GARP, as well as using a more recent climate change model (HadGEM2) considered to have better performance at higher resolution than the earlier one (HadCM2). Lutzomyia intermedia was shown to be the more tropical of the two species, with its climatic niche defined by higher annual mean temperatures and lower temperature seasonality, in contrast to the more subtropical L. neivai. These different latitudinal ranges explain the two species' predicted responses to climate change by 2050, with L. intermedia mostly contracting its range (except perhaps in northeast Brazil) and L. neivai mostly shifting its range southwards in Brazil and Argentina. This contradicts the findings of the 2003 report, which predicted more range expansion. The different findings can be explained by the improved data sets and modelling methods. Our

The map-1 gene family in root-knot nematodes, Meloidogyne spp.: a set of taxonomically restricted genes specific to clonal species.

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Iva Tomalova

Full Text Available Taxonomically restricted genes (TRGs, i.e., genes that are restricted to a limited subset of phylogenetically related organisms, may be important in adaptation. In parasitic organisms, TRG-encoded proteins are possible determinants of the specificity of host-parasite interactions. In the root-knot nematode (RKN Meloidogyne incognita, the map-1 gene family encodes expansin-like proteins that are secreted into plant tissues during parasitism, thought to act as effectors to promote successful root infection. MAP-1 proteins exhibit a modular architecture, with variable number and arrangement of 58 and 13-aa domains in their central part. Here, we address the evolutionary origins of this gene family using a combination of bioinformatics and molecular biology approaches. Map-1 genes were solely identified in one single member of the phylum Nematoda, i.e., the genus Meloidogyne, and not detected in any other nematode, thus indicating that the map-1 gene family is indeed a TRG family. A phylogenetic analysis of the distribution of map-1 genes in RKNs further showed that these genes are specifically present in species that reproduce by mitotic parthenogenesis, with the exception of M. floridensis, and could not be detected in RKNs reproducing by either meiotic parthenogenesis or amphimixis. These results highlight the divergence between mitotic and meiotic RKN species as a critical transition in the evolutionary history of these parasites. Analysis of the sequence conservation and organization of repeated domains in map-1 genes suggests that gene duplication(s together with domain loss/duplication have contributed to the evolution of the map-1 family, and that some strong selection mechanism may be acting upon these genes to maintain their functional role(s in the specificity of the plant-RKN interactions.

Gene-specific cell labeling using MiMIC transposons.

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Gnerer, Joshua P; Venken, Koen J T; Dierick, Herman A

2015-04-30

Binary expression systems such as GAL4/UAS, LexA/LexAop and QF/QUAS have greatly enhanced the power of Drosophila as a model organism by allowing spatio-temporal manipulation of gene function as well as cell and neural circuit function. Tissue-specific expression of these heterologous transcription factors relies on random transposon integration near enhancers or promoters that drive the binary transcription factor embedded in the transposon. Alternatively, gene-specific promoter elements are directly fused to the binary factor within the transposon followed by random or site-specific integration. However, such insertions do not consistently recapitulate endogenous expression. We used Minos-Mediated Integration Cassette (MiMIC) transposons to convert host loci into reliable gene-specific binary effectors. MiMIC transposons allow recombinase-mediated cassette exchange to modify the transposon content. We developed novel exchange cassettes to convert coding intronic MiMIC insertions into gene-specific binary factor protein-traps. In addition, we expanded the set of binary factor exchange cassettes available for non-coding intronic MiMIC insertions. We show that binary factor conversions of different insertions in the same locus have indistinguishable expression patterns, suggesting that they reliably reflect endogenous gene expression. We show the efficacy and broad applicability of these new tools by dissecting the cellular expression patterns of the Drosophila serotonin receptor gene family. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Endothelial Progenitor Cell Dysfunction in Myelodysplastic Syndromes: Possible Contribution of a Defective Vascular Niche to Myelodysplasia

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Luciana Teofili

2015-05-01

Full Text Available We set a model to replicate the vascular bone marrow niche by using endothelial colony forming cells (ECFCs, and we used it to explore the vascular niche function in patients with low-risk myelodysplastic syndromes (MDS. Overall, we investigated 56 patients and we observed higher levels of ECFCs in MDS than in healthy controls; moreover, MDS ECFCs were found variably hypermethylated for p15INK4b DAPK1, CDH1, or SOCS1. MDS ECFCs exhibited a marked adhesive capacity to normal mononuclear cells. When normal CD34+ cells were co-cultured with MDS ECFCs, they generated significant lower amounts of CD11b+ and CD41+ cells than in co-culture with normal ECFCs. At gene expression profile, several genes involved in cell adhesion were upregulated in MDS ECFCs, while several members of the Wingless and int (Wnt pathways were underexpressed. Furthermore, at miRNA expression profile, MDS ECFCs hypo-expressed various miRNAs involved in Wnt pathway regulation. The addition of Wnt3A reduced the expression of intercellular cell adhesion molecule-1 on MDS ECFCs and restored the defective expression of markers of differentiation. Overall, our data demonstrate that in low-risk MDS, ECFCs exhibit various primary abnormalities, including putative MDS signatures, and suggest the possible contribution of the vascular niche dysfunction to myelodysplasia.

Genome-wide strategies identify downstream target genes of chick connective tissue-associated transcription factors.

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Orgeur, Mickael; Martens, Marvin; Leonte, Georgeta; Nassari, Sonya; Bonnin, Marie-Ange; Börno, Stefan T; Timmermann, Bernd; Hecht, Jochen; Duprez, Delphine; Stricker, Sigmar

2018-03-29

Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc-finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling of chick limb micromass cultures revealed a set of common genes regulated by all five transcription factors, which we describe as a connective tissue core expression set. This common core was enriched with genes associated with axon guidance and myofibroblast signature, including fibrosis-related genes. In addition, each transcription factor regulated a specific set of signalling molecules and extracellular matrix components. This suggests a concept whereby local molecular niches can be created by the expression of specific transcription factors impinging on the specification of local microenvironments. The regulatory network established here identifies common and distinct molecular signatures of limb connective tissue subtypes, provides novel insight into the signalling pathways governing connective tissue specification, and serves as a resource for connective tissue development. © 2018. Published by The Company of Biologists Ltd.

Ecological niche of plant pathogens

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Ecaterina Fodor

2011-06-01

Full Text Available Disease ecology is a new approach to the understanding of the spread and dynamics of pathogens in natural and man-made environments. Defining and describing the ecological niche of the pathogens is one of the major tasks for ecological theory, as well as for practitioners preoccupied with the control and forecasting of established and emerging diseases. Niche theory has been periodically revised, not including in an explicit way the pathogens. However, many progresses have been achieved in niche modeling of disease spread, but few attempts were made to construct a theoretical frame for the ecological niche of pathogens. The paper is a review of the knowledge accumulated during last decades in the niche theory of pathogens and proposes an ecological approach in research. It quest for new control methods in what concerns forest plant pathogens, with a special emphasis on fungi like organisms of the genus Phytophthora. Species of Phytophthora are the most successful plant pathogens of the moment, affecting forest and agricultural systems worldwide, many of them being invasive alien organisms in many ecosystems. The hyperspace of their ecological niche is defined by hosts, environment and human interference, as main axes. To select most important variables within the hyperspace, is important the understanding of the complex role of pathogens in the ecosystems as well as for control programs. Biotic relationships within ecosystem of host-pathogen couple are depicted by ecological network and specific metrics attached to this. The star shaped network is characterized by few high degree nodes, by short path lengths and relatively low connectivity, premises for a rapid disturbance spread. 

Ecological niche of plant pathogens

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Ecaterina Fodor

2011-02-01

Full Text Available Disease ecology is a new approach to the understanding of the spread and dynamics of pathogens in natural and man-made environments. Defining and describing the ecological niche of the pathogens is one of the major tasks for ecological theory, as well as for practitioners preoccupied with the control and forecasting of established and emerging diseases. Niche theory has been periodically revised, not including in an explicit way the pathogens. However, many progresses have been achieved in niche modeling of disease spread, but few attempts were made to construct a theoretical frame for the ecological niche of pathogens. The paper is a review of the knowledge accumulated during last decades in the niche theory of pathogens and proposes an ecological approach in research. It quest for new control methods in what concerns forest plant pathogens, with a special emphasis on fungi like organisms of the genus Phytophthora. Species of Phytophthora are the most successful plant pathogens of the moment, affecting forest and agricultural systems worldwide, many of them being invasive alien organisms in many ecosystems. The hyperspace of their ecological niche is defined by hosts, environment and human interference, as main axes. To select most important variables within the hyperspace, is important for the understanding of the complex role of pathogens in the ecosystems as well as for control programs. Biotic relationships within ecosystem of host-pathogen couple are depicted by ecological network and specific metrics attached to this. The star shaped network is characterized by few high degree nodes, by short path lengths and relatively low connectivity, premises for a rapid disturbance spread.

α6-Integrin alternative splicing: distinct cytoplasmic variants in stem cell fate specification and niche interaction.

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Zhou, Zijing; Qu, Jing; He, Li; Peng, Hong; Chen, Ping; Zhou, Yong

2018-05-02

α6-Integrin subunit (also known as CD49f) is a stemness signature that has been found on the plasma membrane of more than 30 stem cell populations. A growing body of studies have focused on the critical role of α6-containing integrins (α6β1 and α6β4) in the regulation of stem cell properties, lineage-specific differentiation, and niche interaction. α6-Integrin subunit can be alternatively spliced at the post-transcriptional level, giving rise to divergent isoforms which differ in the cytoplasmic and/or extracellular domains. The cytoplasmic domain of integrins is an important functional part of integrin-mediated signals. Structural changes in the cytoplasmic domain of α6 provide an efficient means for the regulation of stem cell responses to biochemical stimuli and/or biophysical cues in the stem cell niche, thus impacting stem cell fate determination. In this review, we summarize the current knowledge on the structural variants of the α6-integrin subunit and spatiotemporal expression of α6 cytoplasmic variants in embryonic and adult stem/progenitor cells. We highlight the roles of α6 cytoplasmic variants in stem cell fate decision and niche interaction, and discuss the potential mechanisms involved. Understanding of the distinct functions of α6 splicing variants in stem cell biology may inform the rational design of novel stem cell-based therapies for a range of human diseases.

Ranking metrics in gene set enrichment analysis: do they matter?

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Zyla, Joanna; Marczyk, Michal; Weiner, January; Polanska, Joanna

2017-05-12

There exist many methods for describing the complex relation between changes of gene expression in molecular pathways or gene ontologies under different experimental conditions. Among them, Gene Set Enrichment Analysis seems to be one of the most commonly used (over 10,000 citations). An important parameter, which could affect the final result, is the choice of a metric for the ranking of genes. Applying a default ranking metric may lead to poor results. In this work 28 benchmark data sets were used to evaluate the sensitivity and false positive rate of gene set analysis for 16 different ranking metrics including new proposals. Furthermore, the robustness of the chosen methods to sample size was tested. Using k-means clustering algorithm a group of four metrics with the highest performance in terms of overall sensitivity, overall false positive rate and computational load was established i.e. absolute value of Moderated Welch Test statistic, Minimum Significant Difference, absolute value of Signal-To-Noise ratio and Baumgartner-Weiss-Schindler test statistic. In case of false positive rate estimation, all selected ranking metrics were robust with respect to sample size. In case of sensitivity, the absolute value of Moderated Welch Test statistic and absolute value of Signal-To-Noise ratio gave stable results, while Baumgartner-Weiss-Schindler and Minimum Significant Difference showed better results for larger sample size. Finally, the Gene Set Enrichment Analysis method with all tested ranking metrics was parallelised and implemented in MATLAB, and is available at https://github.com/ZAEDPolSl/MrGSEA . Choosing a ranking metric in Gene Set Enrichment Analysis has critical impact on results of pathway enrichment analysis. The absolute value of Moderated Welch Test has the best overall sensitivity and Minimum Significant Difference has the best overall specificity of gene set analysis. When the number of non-normally distributed genes is high, using Baumgartner

PTEN Signaling in the Postnatal Perivascular Progenitor Niche Drives Medulloblastoma Formation.

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Zhu, Guo; Rankin, Sherri L; Larson, Jon D; Zhu, Xiaoyan; Chow, Lionel M L; Qu, Chunxu; Zhang, Jinghui; Ellison, David W; Baker, Suzanne J

2017-01-01

Loss of the tumor suppressor gene PTEN exerts diverse outcomes on cancer in different developmental contexts. To gain insight into the effect of its loss on outcomes in the brain, we conditionally inactivated the murine Pten gene in neonatal neural stem/progenitor cells. Pten inactivation created an abnormal perivascular proliferative niche in the cerebellum that persisted in adult animals but did not progress to malignancy. Proliferating cells showed undifferentiated morphology and expressed the progenitor marker Nestin but not Math1, a marker of committed granule neuron progenitors. Codeletion of Pten and Trp53 resulted in fully penetrant medulloblastoma originating from the perivascular niche, which exhibited abnormal blood vessel networks and advanced neuronal differentiation of tumor cells. EdU pulse-chase experiments demonstrated a perivascular cancer stem cell population in Pten/Trp53 double mutant medulloblastomas. Genetic analyses revealed recurrent somatic inactivations of the tumor suppressor gene Ptch1 and a recapitulation of the sonic hedgehog subgroup of human medulloblastomas. Overall, our results showed that PTEN acts to prevent the proliferation of a progenitor niche in postnatal cerebellum predisposed to oncogenic induction of medulloblastoma. Cancer Res; 77(1); 123-33. ©2016 AACR. ©2016 American Association for Cancer Research.

Ontogenetic niche shifts and evolutionary branching in size-structured populations

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Claessen, D.; Dieckmann, U.

2002-01-01

There are many examples of size-structured populations where individuals sequentially exploit several niches in the course of their life history. Efficient exploitation of such ontogenetic niches generally requires specific morphological adaptations. Here, we study the evolutionary implications of

Integrative analysis of survival-associated gene sets in breast cancer.

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Varn, Frederick S; Ung, Matthew H; Lou, Shao Ke; Cheng, Chao

2015-03-12

Patient gene expression information has recently become a clinical feature used to evaluate breast cancer prognosis. The emergence of prognostic gene sets that take advantage of these data has led to a rich library of information that can be used to characterize the molecular nature of a patient's cancer. Identifying robust gene sets that are consistently predictive of a patient's clinical outcome has become one of the main challenges in the field. We inputted our previously established BASE algorithm with patient gene expression data and gene sets from MSigDB to develop the gene set activity score (GSAS), a metric that quantitatively assesses a gene set's activity level in a given patient. We utilized this metric, along with patient time-to-event data, to perform survival analyses to identify the gene sets that were significantly correlated with patient survival. We then performed cross-dataset analyses to identify robust prognostic gene sets and to classify patients by metastasis status. Additionally, we created a gene set network based on component gene overlap to explore the relationship between gene sets derived from MSigDB. We developed a novel gene set based on this network's topology and applied the GSAS metric to characterize its role in patient survival. Using the GSAS metric, we identified 120 gene sets that were significantly associated with patient survival in all datasets tested. The gene overlap network analysis yielded a novel gene set enriched in genes shared by the robustly predictive gene sets. This gene set was highly correlated to patient survival when used alone. Most interestingly, removal of the genes in this gene set from the gene pool on MSigDB resulted in a large reduction in the number of predictive gene sets, suggesting a prominent role for these genes in breast cancer progression. The GSAS metric provided a useful medium by which we systematically investigated how gene sets from MSigDB relate to breast cancer patient survival. We used

Effects of ionizing radiation on the hematopoietic niche and treatment of acute radiation syndrome by gene therapy in highly-irradiated monkeys

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Garrigou, Ph.

2011-01-01

The hematopoietic stem cell niche represents a complex radiosensitive compartment whose protection is required for recovery from radiation-induced myelosuppression. We initially studied RI effects on endothelial and mesenchymal progenitors by an evaluating radiosensitivity and cell death. Then, we have proposed a new gene therapy strategy based on local and short term secretion of Sonic hedgehog morphogen to favour vascular niche repair and to stimulate residual hematopoietic stem and progenitor cells. We investigated the hematopoietic response of 8-Gy gamma irradiated monkeys to a single intra-osseous injection of xenogeneic multipotent mesenchymal stem cells transduced with a Shh pIRES2 plasmid. Thrombocytopenia and neutropenia duration were significantly reduced in grafted animals and clonogenics normalized from day 42. Areas under the curve of PLTs and ANCs between day 0 and day 30 were significantly higher in treated animals than in controls. Grafting Matrigel TM colonized or not with ASC in immunocompromised mice demonstrated a notable pro-angiogenic activity for Shh-ASC. Long term follow up (180-300 days) confirmed a durable recovery in the four grafted monkeys. Globally this study suggests that grafting Shh-multipotent stem cells may represent a new strategy to cure radiation-induced niche damage. (author)

Individual diet variation in a marine fish assemblage: Optimal Foraging Theory, Niche Variation Hypothesis and functional identity

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Cachera, M.; Ernande, B.; Villanueva, M. C.; Lefebvre, S.

2017-02-01

Individual diet variation (i.e. diet variation among individuals) impacts intra- and inter-specific interactions. Investigating its sources and relationship with species trophic niche organization is important for understanding community structure and dynamics. Individual diet variation may increase with intra-specific phenotypic (or "individual state") variation and habitat variability, according to Optimal Foraging Theory (OFT), and with species trophic niche width, according to the Niche Variation Hypothesis (NVH). OFT proposes "proximate sources" of individual diet variation such as variations in habitat or size whereas NVH relies on "ultimate sources" related to the competitive balance between intra- and inter-specific competitions. The latter implies as a corollary that species trophic niche overlap, taken as inter-specific competition measure, decreases as species niche width and individual niche variation increase. We tested the complementary predictions of OFT and NVH in a marine fish assemblage using stomach content data and associated trophic niche metrics. The NVH predictions were tested between species of the assemblage and decomposed into a between- and a within-functional group component to assess the potential influence of species' ecological function. For most species, individual diet variation and niche overlap were consistently larger than expected. Individual diet variation increased with intra-specific variability in individual state and habitat, as expected from OFT. It also increased with species niche width but in compliance with the null expectation, thus not supporting the NVH. In contrast, species niche overlap increased significantly less than null expectation with both species niche width and individual diet variation, supporting NVH corollary. The between- and within-functional group components of the NVH relationships were consistent with those between species at the assemblage level. Changing the number of prey categories used to

The Evolution of Two-Component Systems in Bacteria RevealsDifferent Strategies for Niche Adaptation

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Alm, Eric; Huang, Katherine; Arkin, Adam

2006-09-13

Two-component systems including histidine protein kinasesrepresent the primary signal transduction paradigm in prokaryoticorganisms. To understand how these systems adapt to allow organisms todetect niche-specific signals, we analyzed the phylogenetic distributionof nearly 5000 histidine protein kinases from 207 sequenced prokaryoticgenomes. We found that many genomes carry a large repertoire of recentlyevolved signaling genes, which may reflect selective pressure to adapt tonew environmental conditions. Both lineage-specific gene family expansionand horizontal gene transfer play major roles in the introduction of newhistidine kinases into genomes; however, there are differences in howthese two evolutionary forces act. Genes imported via horizontal transferare more likely to retain their original functionality as inferred from asimilar complement of signaling domains, while gene family expansionaccompanied by domain shuffling appears to be a major source of novelgenetic diversity. Family expansion is the dominantsource of newhistidine kinase genes in the genomes most enriched in signalingproteins, and detailed analysis reveals that divergence in domainstructure and changes in expression patterns are hallmarks of recentexpansions. Finally, while these two modes of gene acquisition arewidespread across bacterial taxa, there are clear species-specificpreferences for which mode is used.

Fibrocytes and the tissue niche in lung repair

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Bjermer Leif

2011-06-01

Full Text Available Abstract Human fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of markers related to leukocytes, hematopoietic stem cells and a diverse set of fibroblast phenotypes. Fibrocytes can be recruited from the circulation to the tissue where they further can differentiate and proliferate into various mesenchymal cell types depending on the tissue niche. This local tissue niche is important because it modulates the fibrocytes and coordinates their role in tissue behaviour and repair. However, plasticity of a niche may be co-opted in chronic airway diseases such as asthma, idiopathic pulmonary fibrosis and obliterative bronchiolitis. This review will therefore focus on a possible role of fibrocytes in pathological tissue repair processes in those diseases.

FunGeneNet: a web tool to estimate enrichment of functional interactions in experimental gene sets.

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Tiys, Evgeny S; Ivanisenko, Timofey V; Demenkov, Pavel S; Ivanisenko, Vladimir A

2018-02-09

Estimation of functional connectivity in gene sets derived from genome-wide or other biological experiments is one of the essential tasks of bioinformatics. A promising approach for solving this problem is to compare gene networks built using experimental gene sets with random networks. One of the resources that make such an analysis possible is CrossTalkZ, which uses the FunCoup database. However, existing methods, including CrossTalkZ, do not take into account individual types of interactions, such as protein/protein interactions, expression regulation, transport regulation, catalytic reactions, etc., but rather work with generalized types characterizing the existence of any connection between network members. We developed the online tool FunGeneNet, which utilizes the ANDSystem and STRING to reconstruct gene networks using experimental gene sets and to estimate their difference from random networks. To compare the reconstructed networks with random ones, the node permutation algorithm implemented in CrossTalkZ was taken as a basis. To study the FunGeneNet applicability, the functional connectivity analysis of networks constructed for gene sets involved in the Gene Ontology biological processes was conducted. We showed that the method sensitivity exceeds 0.8 at a specificity of 0.95. We found that the significance level of the difference between gene networks of biological processes and random networks is determined by the type of connections considered between objects. At the same time, the highest reliability is achieved for the generalized form of connections that takes into account all the individual types of connections. By taking examples of the thyroid cancer networks and the apoptosis network, it is demonstrated that key participants in these processes are involved in the interactions of those types by which these networks differ from random ones. FunGeneNet is a web tool aimed at proving the functionality of networks in a wide range of sizes of

Range bagging: a new method for ecological niche modelling from presence-only data.

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Drake, John M

2015-06-06

The ecological niche is the set of environments in which a population of a species can persist without introduction of individuals from other locations. A good mathematical or computational representation of the niche is a prerequisite to addressing many questions in ecology, biogeography, evolutionary biology and conservation. A particularly challenging question for ecological niche modelling is the problem of presence-only modelling. That is, can an ecological niche be identified from records drawn only from the set of niche environments without records from non-niche environments for comparison? Here, I introduce a new method for ecological niche modelling from presence-only data called range bagging. Range bagging draws on the concept of a species' environmental range, but was inspired by the empirical performance of ensemble learning algorithms in other areas of ecological research. This paper extends the concept of environmental range to multiple dimensions and shows that range bagging is computationally feasible even when the number of environmental dimensions is large. The target of the range bagging base learner is an environmental tolerance of the species in a projection of its niche and is therefore an ecologically interpretable property of a species' biological requirements. The computational complexity of range bagging is linear in the number of examples, which compares favourably with the main alternative, Qhull. In conclusion, range bagging appears to be a reasonable choice for niche modelling in applications in which a presence-only method is desired and may provide a solution to problems in other disciplines where one-class classification is required, such as outlier detection and concept learning.

Incorporation of gene-specific variability improves expression analysis using high-density DNA microarrays

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Spitznagel Edward

2003-11-01

Full Text Available Abstract Background The assessment of data reproducibility is essential for application of microarray technology to exploration of biological pathways and disease states. Technical variability in data analysis largely depends on signal intensity. Within that context, the reproducibility of individual probe sets has not been hitherto addressed. Results We used an extraordinarily large replicate data set derived from human placental trophoblast to analyze probe-specific contribution to variability of gene expression. We found that signal variability, in addition to being signal-intensity dependant, is probe set-specific. Importantly, we developed a novel method to quantify the contribution of this probe set-specific variability. Furthermore, we devised a formula that incorporates a priori-computed, replicate-based information on probe set- and intensity-specific variability in determination of expression changes even without technical replicates. Conclusion The strategy of incorporating probe set-specific variability is superior to analysis based on arbitrary fold-change thresholds. We recommend its incorporation to any computation of gene expression changes using high-density DNA microarrays. A Java application implementing our T-score is available at http://www.sadovsky.wustl.edu/tscore.html.

Proximity-based differential single cell analysis of the niche to identify stem/progenitor cell regulators

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Silberstein, Lev; Goncalves, Kevin A; Kharchenko, Peter V; Turcotte, Raphael; Kfoury, Youmna; Mercier, Francois; Baryawno, Ninib; Severe, Nicolas; Bachand, Jacqueline; Spencer, Joel; Papazian, Ani; Lee, Dongjun; Chitteti, Brahmananda Reddy; Srour, Edward F; Hoggatt, Jonathan; Tate, Tiffany; Celso, Cristina Lo; Ono, Noriaki; Nutt, Stephen; Heino, Jyrki; Sipilä, Kalle; Shioda, Toshihiro; Osawa, Masatake; Lin, Charles P; Hu, Guo-fu; Scadden, David T

2016-01-01

SUMMARY Physiological stem cell function is regulated by secreted factors produced by niche cells. In this study, we describe an unbiased approach based on differential single-cell gene expression analysis of mesenchymal osteolineage cells close to and further removed from hematopoietic stem/progenitor cells to identify candidate niche factors. Mesenchymal cells displayed distinct molecular profiles based on their relative location. Amongst the genes which were preferentially expressed in proximal cells, we functionally examined three secreted or cell surface molecules not previously connected to HSPC biology: the secreted RNase Angiogenin, the cytokine IL18 and the adhesion molecule Embigin and discovered that all of these factors are HSPC quiescence regulators. Our proximity-based differential single cell approach therefore reveals molecular heterogeneity within niche cells and can be used to identify novel extrinsic stem/progenitor cell regulators. Similar approaches could also be applied to other stem cell/niche pairs to advance understanding of microenvironmental regulation of stem cell function. PMID:27524439

Haematopoietic stem cell niches: new insights inspire new questions

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Ugarte, Fernando; Forsberg, E Camilla

2013-01-01

Haematopoietic stem cell (HSC) niches provide an environment essential for life-long HSC function. Intense investigation of HSC niches both feed off and drive technology development to increase our capability to assay functionally defined cells with high resolution. A major driving force behind the desire to understand the basic biology of HSC niches is the clear implications for clinical therapies. Here, with particular emphasis on cell type-specific deletion of SCL and CXCL12, we focus on unresolved issues on HSC niches, framed around some very recent advances and novel discoveries on the extrinsic regulation of HSC maintenance. We also provide ideas for possible paths forward, some of which are clearly within reach while others will require both novel tools and vision. PMID:24022369

Niche construction, sources of selection and trait coevolution.

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Laland, Kevin; Odling-Smee, John; Endler, John

2017-10-06

Organisms modify and choose components of their local environments. This 'niche construction' can alter ecological processes, modify natural selection and contribute to inheritance through ecological legacies. Here, we propose that niche construction initiates and modifies the selection directly affecting the constructor, and on other species, in an orderly, directed and sustained manner. By dependably generating specific environmental states, niche construction co-directs adaptive evolution by imposing a consistent statistical bias on selection. We illustrate how niche construction can generate this evolutionary bias by comparing it with artificial selection. We suggest that it occupies the middle ground between artificial and natural selection. We show how the perspective leads to testable predictions related to: (i) reduced variance in measures of responses to natural selection in the wild; (ii) multiple trait coevolution, including the evolution of sequences of traits and patterns of parallel evolution; and (iii) a positive association between niche construction and biodiversity. More generally, we submit that evolutionary biology would benefit from greater attention to the diverse properties of all sources of selection.

Large scale gene expression meta-analysis reveals tissue-specific, sex-biased gene expression in humans

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Benjamin Mayne

2016-10-01

Full Text Available The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analysed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes, followed by the heart (375 genes, kidney (224 genes, colon (218 genes and thyroid (163 genes. More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases.

MAGMA: Generalized Gene-Set Analysis of GWAS Data

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de Leeuw, C.A.; Mooij, J.M.; Heskes, T.; Posthuma, D.

2015-01-01

By aggregating data for complex traits in a biologically meaningful way, gene and gene-set analysis constitute a valuable addition to single-marker analysis. However, although various methods for gene and gene-set analysis currently exist, they generally suffer from a number of issues. Statistical

MAGMA: generalized gene-set analysis of GWAS data.

NARCIS (Netherlands)

de Leeuw, C.A.; Mooij, J.M.; Heskes, T.; Posthuma, D.

2015-01-01

By aggregating data for complex traits in a biologically meaningful way, gene and gene-set analysis constitute a valuable addition to single-marker analysis. However, although various methods for gene and gene-set analysis currently exist, they generally suffer from a number of issues. Statistical

Gene set analysis of purine and pyrimidine antimetabolites cancer therapies.

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Fridley, Brooke L; Batzler, Anthony; Li, Liang; Li, Fang; Matimba, Alice; Jenkins, Gregory D; Ji, Yuan; Wang, Liewei; Weinshilboum, Richard M

2011-11-01

Responses to therapies, either with regard to toxicities or efficacy, are expected to involve complex relationships of gene products within the same molecular pathway or functional gene set. Therefore, pathways or gene sets, as opposed to single genes, may better reflect the true underlying biology and may be more appropriate units for analysis of pharmacogenomic studies. Application of such methods to pharmacogenomic studies may enable the detection of more subtle effects of multiple genes in the same pathway that may be missed by assessing each gene individually. A gene set analysis of 3821 gene sets is presented assessing the association between basal messenger RNA expression and drug cytotoxicity using ethnically defined human lymphoblastoid cell lines for two classes of drugs: pyrimidines [gemcitabine (dFdC) and arabinoside] and purines [6-thioguanine and 6-mercaptopurine]. The gene set nucleoside-diphosphatase activity was found to be significantly associated with both dFdC and arabinoside, whereas gene set γ-aminobutyric acid catabolic process was associated with dFdC and 6-thioguanine. These gene sets were significantly associated with the phenotype even after adjusting for multiple testing. In addition, five associated gene sets were found in common between the pyrimidines and two gene sets for the purines (3',5'-cyclic-AMP phosphodiesterase activity and γ-aminobutyric acid catabolic process) with a P value of less than 0.0001. Functional validation was attempted with four genes each in gene sets for thiopurine and pyrimidine antimetabolites. All four genes selected from the pyrimidine gene sets (PSME3, CANT1, ENTPD6, ADRM1) were validated, but only one (PDE4D) was validated for the thiopurine gene sets. In summary, results from the gene set analysis of pyrimidine and purine therapies, used often in the treatment of various cancers, provide novel insight into the relationship between genomic variation and drug response.

Gene set analysis for GWAS

DEFF Research Database (Denmark)

Debrabant, Birgit; Soerensen, Mette

2014-01-01

Abstract We discuss the use of modified Kolmogorov-Smirnov (KS) statistics in the context of gene set analysis and review corresponding null and alternative hypotheses. Especially, we show that, when enhancing the impact of highly significant genes in the calculation of the test statistic, the co...

A hybrid approach of gene sets and single genes for the prediction of survival risks with gene expression data.

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Seok, Junhee; Davis, Ronald W; Xiao, Wenzhong

2015-01-01

Accumulated biological knowledge is often encoded as gene sets, collections of genes associated with similar biological functions or pathways. The use of gene sets in the analyses of high-throughput gene expression data has been intensively studied and applied in clinical research. However, the main interest remains in finding modules of biological knowledge, or corresponding gene sets, significantly associated with disease conditions. Risk prediction from censored survival times using gene sets hasn't been well studied. In this work, we propose a hybrid method that uses both single gene and gene set information together to predict patient survival risks from gene expression profiles. In the proposed method, gene sets provide context-level information that is poorly reflected by single genes. Complementarily, single genes help to supplement incomplete information of gene sets due to our imperfect biomedical knowledge. Through the tests over multiple data sets of cancer and trauma injury, the proposed method showed robust and improved performance compared with the conventional approaches with only single genes or gene sets solely. Additionally, we examined the prediction result in the trauma injury data, and showed that the modules of biological knowledge used in the prediction by the proposed method were highly interpretable in biology. A wide range of survival prediction problems in clinical genomics is expected to benefit from the use of biological knowledge.

Habitat niche breadth predicts invasiveness in solitary ascidians.

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Granot, Itai; Shenkar, Noa; Belmaker, Jonathan

2017-10-01

A major focus of invasion biology is understanding the traits associated with introduction success. Most studies assess these traits in the invaded region, while only few compare nonindigenous species to the pool of potential invaders in their native region. We focused on the niche breadth hypothesis , commonly evoked but seldom tested, which states that generalist species are more likely to become introduced as they are capable of thriving under a wide set of conditions. Based on the massive introduction of tropical species into the Mediterranean via the Suez Canal (Lessepsian migration), we defined ascidians in the Red Sea as the pool of potential invaders. We constructed unique settlement plates, each representing six different niches, to assess ascidian niche breadth, and deployed them in similar habitats in the native and invaded regions. For each species found on plates, we evaluated its abundance, relative abundance across successional stages, and niche breadth, and then compared (1) species in the Red Sea known to have been introduced into the Mediterranean (Lessepsian species) and those not known from the Mediterranean (non-Lessepsian); and (2) nonindigenous and indigenous species in the Mediterranean. Lessepsian species identified on plates in the Red Sea demonstrated wider niche breadth than non-Lessepsian species, supporting the niche breadth hypothesis within the native region. No differences were found between Lessepsian and non-Lessepsian species in species abundance and successional stages. In the Mediterranean, nonindigenous species numerically dominated the settlement plates. This precluded robust comparisons of niche breadth between nonindigenous and indigenous species in the invaded region. In conclusion, using Red Sea ascidians as the pool of potential invaders, we found clear evidence supporting the niche breadth hypothesis in the native region. We suggest that such patterns may often be obscured when conducting trait-based studies in the

Inter-specific and seasonal comparison of the niches occupied by small cetaceans off north-west Iberia

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Fernandez Garcia, Rut; MacLeod, C. D.; Pierce, G. J.

2013-01-01

Knowledge of species' ecological niches can be used to assess ecological interactions between different taxa. Sixteen species of cetaceans have been recorded in Galician waters and niche partitioning is expected to occur among these species in order to allow them to co-exist. In this study, the n...

Evaluating the consistency of gene sets used in the analysis of bacterial gene expression data

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Tintle Nathan L

2012-08-01

Full Text Available Abstract Background Statistical analyses of whole genome expression data require functional information about genes in order to yield meaningful biological conclusions. The Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG are common sources of functionally grouped gene sets. For bacteria, the SEED and MicrobesOnline provide alternative, complementary sources of gene sets. To date, no comprehensive evaluation of the data obtained from these resources has been performed. Results We define a series of gene set consistency metrics directly related to the most common classes of statistical analyses for gene expression data, and then perform a comprehensive analysis of 3581 Affymetrix® gene expression arrays across 17 diverse bacteria. We find that gene sets obtained from GO and KEGG demonstrate lower consistency than those obtained from the SEED and MicrobesOnline, regardless of gene set size. Conclusions Despite the widespread use of GO and KEGG gene sets in bacterial gene expression data analysis, the SEED and MicrobesOnline provide more consistent sets for a wide variety of statistical analyses. Increased use of the SEED and MicrobesOnline gene sets in the analysis of bacterial gene expression data may improve statistical power and utility of expression data.

Studying the Complex Expression Dependences between Sets of Coexpressed Genes

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Mario Huerta

2014-01-01

Full Text Available Organisms simplify the orchestration of gene expression by coregulating genes whose products function together in the cell. The use of clustering methods to obtain sets of coexpressed genes from expression arrays is very common; nevertheless there are no appropriate tools to study the expression networks among these sets of coexpressed genes. The aim of the developed tools is to allow studying the complex expression dependences that exist between sets of coexpressed genes. For this purpose, we start detecting the nonlinear expression relationships between pairs of genes, plus the coexpressed genes. Next, we form networks among sets of coexpressed genes that maintain nonlinear expression dependences between all of them. The expression relationship between the sets of coexpressed genes is defined by the expression relationship between the skeletons of these sets, where this skeleton represents the coexpressed genes with a well-defined nonlinear expression relationship with the skeleton of the other sets. As a result, we can study the nonlinear expression relationships between a target gene and other sets of coexpressed genes, or start the study from the skeleton of the sets, to study the complex relationships of activation and deactivation between the sets of coexpressed genes that carry out the different cellular processes present in the expression experiments.

Widespread correlations between climatic niche evolution and species diversification in birds.

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Cooney, Christopher R; Seddon, Nathalie; Tobias, Joseph A

2016-07-01

The adaptability of species' climatic niches can influence the dynamics of colonization and gene flow across climatic gradients, potentially increasing the likelihood of speciation or reducing extinction in the face of environmental change. However, previous comparative studies have tested these ideas using geographically, taxonomically and ecologically restricted samples, yielding mixed results, and thus the processes linking climatic niche evolution with diversification remain poorly understood. Focusing on birds, the largest and most widespread class of terrestrial vertebrates, we test whether variation in species diversification among clades is correlated with rates of climatic niche evolution and the extent to which these patterns are modified by underlying gradients in biogeography and species' ecology. We quantified climatic niches, latitudinal distribution and ecological traits for 7657 (˜75%) bird species based on geographical range polygons and then used Bayesian phylogenetic analyses to test whether niche evolution was related to species richness and rates of diversification across genus- and family-level clades. We found that the rate of climatic niche evolution has a positive linear relationship with both species richness and diversification rate at two different taxonomic levels (genus and family). Furthermore, this positive association between labile climatic niches and diversification was detected regardless of variation in clade latitude or key ecological traits. Our findings suggest either that rapid adaptation to unoccupied areas of climatic niche space promotes avian diversification, or that diversification promotes adaptation. Either way, we propose that climatic niche evolution is a fundamental process regulating the link between climate and biodiversity at global scales, irrespective of the geographical and ecological context of speciation and extinction. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

Using the gene ontology to scan multilevel gene sets for associations in genome wide association studies.

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Schaid, Daniel J; Sinnwell, Jason P; Jenkins, Gregory D; McDonnell, Shannon K; Ingle, James N; Kubo, Michiaki; Goss, Paul E; Costantino, Joseph P; Wickerham, D Lawrence; Weinshilboum, Richard M

2012-01-01

Gene-set analyses have been widely used in gene expression studies, and some of the developed methods have been extended to genome wide association studies (GWAS). Yet, complications due to linkage disequilibrium (LD) among single nucleotide polymorphisms (SNPs), and variable numbers of SNPs per gene and genes per gene-set, have plagued current approaches, often leading to ad hoc "fixes." To overcome some of the current limitations, we developed a general approach to scan GWAS SNP data for both gene-level and gene-set analyses, building on score statistics for generalized linear models, and taking advantage of the directed acyclic graph structure of the gene ontology when creating gene-sets. However, other types of gene-set structures can be used, such as the popular Kyoto Encyclopedia of Genes and Genomes (KEGG). Our approach combines SNPs into genes, and genes into gene-sets, but assures that positive and negative effects of genes on a trait do not cancel. To control for multiple testing of many gene-sets, we use an efficient computational strategy that accounts for LD and provides accurate step-down adjusted P-values for each gene-set. Application of our methods to two different GWAS provide guidance on the potential strengths and weaknesses of our proposed gene-set analyses. © 2011 Wiley Periodicals, Inc.

Specific Gene Loci of Clinical Pseudomonas putida Isolates.

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Lázaro Molina

Full Text Available Pseudomonas putida are ubiquitous inhabitants of soils and clinical isolates of this species have been seldom described. Clinical isolates show significant variability in their ability to cause damage to hosts because some of them are able to modulate the host's immune response. In the current study, comparisons between the genomes of different clinical and environmental strains of P. putida were done to identify genetic clusters shared by clinical isolates that are not present in environmental isolates. We show that in clinical strains specific genes are mostly present on transposons, and that this set of genes exhibit high identity with genes found in pathogens and opportunistic pathogens. The set of genes prevalent in P. putida clinical isolates, and absent in environmental isolates, are related with survival under oxidative stress conditions, resistance against biocides, amino acid metabolism and toxin/antitoxin (TA systems. This set of functions have influence in colonization and survival within human tissues, since they avoid host immune response or enhance stress resistance. An in depth bioinformatic analysis was also carried out to identify genetic clusters that are exclusive to each of the clinical isolates and that correlate with phenotypical differences between them, a secretion system type III-like was found in one of these clinical strains, a determinant of pathogenicity in Gram-negative bacteria.

Application of biclustering of gene expression data and gene set enrichment analysis methods to identify potentially disease causing nanomaterials

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Andrew Williams

2015-12-01

Full Text Available Background: The presence of diverse types of nanomaterials (NMs in commerce is growing at an exponential pace. As a result, human exposure to these materials in the environment is inevitable, necessitating the need for rapid and reliable toxicity testing methods to accurately assess the potential hazards associated with NMs. In this study, we applied biclustering and gene set enrichment analysis methods to derive essential features of altered lung transcriptome following exposure to NMs that are associated with lung-specific diseases. Several datasets from public microarray repositories describing pulmonary diseases in mouse models following exposure to a variety of substances were examined and functionally related biclusters of genes showing similar expression profiles were identified. The identified biclusters were then used to conduct a gene set enrichment analysis on pulmonary gene expression profiles derived from mice exposed to nano-titanium dioxide (nano-TiO2, carbon black (CB or carbon nanotubes (CNTs to determine the disease significance of these data-driven gene sets.Results: Biclusters representing inflammation (chemokine activity, DNA binding, cell cycle, apoptosis, reactive oxygen species (ROS and fibrosis processes were identified. All of the NM studies were significant with respect to the bicluster related to chemokine activity (DAVID; FDR p-value = 0.032. The bicluster related to pulmonary fibrosis was enriched in studies where toxicity induced by CNT and CB studies was investigated, suggesting the potential for these materials to induce lung fibrosis. The pro-fibrogenic potential of CNTs is well established. Although CB has not been shown to induce fibrosis, it induces stronger inflammatory, oxidative stress and DNA damage responses than nano-TiO2 particles.Conclusion: The results of the analysis correctly identified all NMs to be inflammogenic and only CB and CNTs as potentially fibrogenic. In addition to identifying several

Proximity-Based Differential Single-Cell Analysis of the Niche to Identify Stem/Progenitor Cell Regulators.

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Silberstein, Lev; Goncalves, Kevin A; Kharchenko, Peter V; Turcotte, Raphael; Kfoury, Youmna; Mercier, Francois; Baryawno, Ninib; Severe, Nicolas; Bachand, Jacqueline; Spencer, Joel A; Papazian, Ani; Lee, Dongjun; Chitteti, Brahmananda Reddy; Srour, Edward F; Hoggatt, Jonathan; Tate, Tiffany; Lo Celso, Cristina; Ono, Noriaki; Nutt, Stephen; Heino, Jyrki; Sipilä, Kalle; Shioda, Toshihiro; Osawa, Masatake; Lin, Charles P; Hu, Guo-Fu; Scadden, David T

2016-10-06

Physiological stem cell function is regulated by secreted factors produced by niche cells. In this study, we describe an unbiased approach based on the differential single-cell gene expression analysis of mesenchymal osteolineage cells close to, and further removed from, hematopoietic stem/progenitor cells (HSPCs) to identify candidate niche factors. Mesenchymal cells displayed distinct molecular profiles based on their relative location. We functionally examined, among the genes that were preferentially expressed in proximal cells, three secreted or cell-surface molecules not previously connected to HSPC biology-the secreted RNase angiogenin, the cytokine IL18, and the adhesion molecule Embigin-and discovered that all of these factors are HSPC quiescence regulators. Therefore, our proximity-based differential single-cell approach reveals molecular heterogeneity within niche cells and can be used to identify novel extrinsic stem/progenitor cell regulators. Similar approaches could also be applied to other stem cell/niche pairs to advance the understanding of microenvironmental regulation of stem cell function. Copyright © 2016 Elsevier Inc. All rights reserved.

Development of a laboratory niche Web site.

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Dimenstein, Izak B; Dimenstein, Simon I

2013-10-01

This technical note presents the development of a methodological laboratory niche Web site. The "Grossing Technology in Surgical Pathology" (www.grossing-technology.com) Web site is used as an example. Although common steps in creation of most Web sites are followed, there are particular requirements for structuring the template's menu on methodological laboratory Web sites. The "nested doll principle," in which one object is placed inside another, most adequately describes the methodological approach to laboratory Web site design. Fragmentation in presenting the Web site's material highlights the discrete parts of the laboratory procedure. An optimally minimal triad of components can be recommended for the creation of a laboratory niche Web site: a main set of media, a blog, and an ancillary component (host, contact, and links). The inclusion of a blog makes the Web site a dynamic forum for professional communication. By forming links and portals, cloud computing opens opportunities for connecting a niche Web site with other Web sites and professional organizations. As an additional source of information exchange, methodological laboratory niche Web sites are destined to parallel both traditional and new forms, such as books, journals, seminars, webinars, and internal educational materials. Copyright © 2013 Elsevier Inc. All rights reserved.

The muscle stem cell niche : regulation of satellite cells during regeneration

NARCIS (Netherlands)

Boonen, K.J.M.; Post, M.J.

2008-01-01

Satellite cells are considered to be adult skeletal muscle stem cells. Their ability to regenerate large muscle defects is highly dependent on their specific niche. When these cells are cultured in vitro, the loss of this niche leads to a loss of proliferative capacity and defective regeneration

Why developmental niche construction is not selective niche construction: and why it matters.

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Stotz, Karola

2017-10-06

In the last decade, niche construction has been heralded as the neglected process in evolution. But niche construction is just one way in which the organism's interaction with and construction of the environment can have potential evolutionary significance. The constructed environment does not just select for , it also produces new variation. Nearly 3 decades ago, and in parallel with Odling-Smee's article 'Niche-constructing phenotypes', West and King introduced the 'ontogenetic niche' to give the phenomena of exo genetic inheritance a formal name. Since then, a range of fields in the life sciences and medicine has amassed evidence that parents influence their offspring by means other than DNA (parental effects), and proposed mechanisms for how heritable variation can be environmentally induced and developmentally regulated. The concept of 'developmental niche construction' (DNC) elucidates how a diverse range of mechanisms contributes to the transgenerational transfer of developmental resources. My most central of claims is that whereas the selective niche of niche construction theory is primarily used to explain the active role of the organism in its selective environment, DNC is meant to indicate the active role of the organism in its developmental environment. The paper highlights the differences between the construction of the selective and the developmental niche, and explores the overall significance of DNC for evolutionary theory.

The null hypothesis of GSEA, and a novel statistical model for competitive gene set analysis

DEFF Research Database (Denmark)

Debrabant, Birgit

2017-01-01

MOTIVATION: Competitive gene set analysis intends to assess whether a specific set of genes is more associated with a trait than the remaining genes. However, the statistical models assumed to date to underly these methods do not enable a clear cut formulation of the competitive null hypothesis....... This is a major handicap to the interpretation of results obtained from a gene set analysis. RESULTS: This work presents a hierarchical statistical model based on the notion of dependence measures, which overcomes this problem. The two levels of the model naturally reflect the modular structure of many gene set...... analysis methods. We apply the model to show that the popular GSEA method, which recently has been claimed to test the self-contained null hypothesis, actually tests the competitive null if the weight parameter is zero. However, for this result to hold strictly, the choice of the dependence measures...

Stitch the niche - a practical philosophy and visual schematic for the niche concept

NARCIS (Netherlands)

McInerny, Greg J.; Etienne, Rampal S.

2012-01-01

By over-focusing on precise definitions, ecology has produced a confused idea of the niche concept. This, our second paper, develops a practical philosophy for the niche that approaches the concept at the correct level of abstraction. We deconstruct the niche into effect and response components and

Periarteriolar Glioblastoma Stem Cell Niches Express Bone Marrow Hematopoietic Stem Cell Niche Proteins

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Hira, Vashendriya V. V.; Wormer, Jill R.; Kakar, Hala; Breznik, Barbara; van der Swaan, Britt; Hulsbos, Renske; Tigchelaar, Wikky; Tonar, Zbynek; Khurshed, Mohammed; Molenaar, Remco J.; van Noorden, Cornelis J. F.

2018-01-01

In glioblastoma, a fraction of malignant cells consists of therapy-resistant glioblastoma stem cells (GSCs) residing in protective niches that recapitulate hematopoietic stem cell (HSC) niches in bone marrow. We have previously shown that HSC niche proteins stromal cell-derived factor-1α (SDF-1α),

Allele-specific gene expression in a wild nonhuman primate population

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Tung, J.; Akinyi, M. Y.; Mutura, S.; Altmann, J.; Wray, G. A.; Alberts, S. C.

2015-01-01

Natural populations hold enormous potential for evolutionary genetic studies, especially when phenotypic, genetic and environmental data are all available on the same individuals. However, untangling the genotype-phenotype relationship in natural populations remains a major challenge. Here, we describe results of an investigation of one class of phenotype, allele-specific gene expression (ASGE), in the well-studied natural population of baboons of the Amboseli basin, Kenya. ASGE measurements identify cases in which one allele of a gene is overexpressed relative to the alternative allele of the same gene, within individuals, thus providing a control for background genetic and environmental effects. Here, we characterize the incidence of ASGE in the Amboseli baboon population, focusing on the genetic and environmental contributions to ASGE in a set of eleven genes involved in immunity and defence. Within this set, we identify evidence for common ASGE in four genes. We also present examples of two relationships between cis-regulatory genetic variants and the ASGE phenotype. Finally, we identify one case in which this relationship is influenced by a novel gene-environment interaction. Specifically, the dominance rank of an individual’s mother during its early life (an aspect of that individual’s social environment) influences the expression of the gene CCL5 via an interaction with cis-regulatory genetic variation. These results illustrate how environmental and ecological data can be integrated into evolutionary genetic studies of functional variation in natural populations. They also highlight the potential importance of early life environmental variation in shaping the genetic architecture of complex traits in wild mammals. PMID:21226779

The Fluctuation Niche in Plants

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Jaume Terradas

2009-01-01

Full Text Available Classical approaches to niche in coexisting plants have undervalued temporal fluctuations. We propose that fluctuation niche is an important dimension of the total niche and interacts with habitat and life-history niches to provide a better understanding of the multidimensional niche space where ecological interactions occur. To scale a fluctuation niche, it is necessary to relate environmental constrictions or species performance not only to the absolute values of the usual environmental and ecophysiological variables but also to their variances or other measures of variability. We use Mediterranean plant communities as examples, because they present characteristic large seasonal and interannual fluctuations in water and nutrient availabilities, along an episodic-constant gradient, and because the plant responses include a number of syndromes coupled to this gradient.

The Fluctuation Niche in Plants

International Nuclear Information System (INIS)

Terradas, J.; Penuelas, J.; Lloret, F.; Penuelas, J.

2009-01-01

Classical approaches to niche in coexisting plants have undervalued temporal fluctuations. We propose that fluctuation niche is an important dimension of the total niche and interacts with habitat and life-history niches to provide a better understanding of the multidimensional niche space where ecological interactions occur. To scale a fluctuation niche, it is necessary to relate environmental constrictions or species performance not only to the absolute values of the usual environmental and eco physiological variables but also to their variances or other measures of variability. We use Mediterranean plant communities as examples, because they present characteristic large seasonal and inter annual fluctuations in water and nutrient availabilities, along an episodic-constant gradient, and because the plant responses include a number of syndromes coupled to this gradient.

Conjugative plasmids: Vessels of the communal gene pool

DEFF Research Database (Denmark)

Norman, Anders; Hansen, Lars H.; Sørensen, Søren Johannes

2009-01-01

to the hosts and, potentially, other resident prokaryotes within specific environmental niches. Insight into the evolution of plasmid modules therefore contributes to our knowledge of gene dissemination and evolution within prokaryotic communities. This communal pool provides the prokaryotes with an important...... mechanistic framework for obtaining adaptability and functional diversity that alleviates the need for large genomes of specialized ‘private genes'....

Niche dimensions in fishes: an integrative view.

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Pörtner, H O; Schulte, P M; Wood, C M; Schiemer, F

2010-01-01

Current shifts in ecosystem composition and function emphasize the need for an understanding of the links between environmental factors and organism fitness and tolerance. The examples discussed here illustrate how recent progress in the field of comparative physiology may provide a better mechanistic understanding of the ecological concepts of the fundamental and realized niches and thus provide insights into the impacts of anthropogenic disturbance. Here we argue that, as a link between physiological and ecological indicators of organismal performance, the mechanisms shaping aerobic scope and passive tolerance set the dimensions of an animal's niche, here defined as its capacity to survive, grow, behave, and interact with other species. We demonstrate how comparative studies of cod or killifish populations in a latitudinal cline have unraveled mitochondrial mechanisms involved in establishing a species' niche, performance, and energy budget. Riverine fish exemplify how the performance windows of various developmental stages follow the dynamic regimes of both seasonal temperatures and river hydrodynamics, as synergistic challenges. Finally, studies of species in extreme environments, such as the tilapia of Lake Magadi, illustrate how on evolutionary timescales functional and morphological shifts can occur, associated with new specializations. We conclude that research on the processes and time course of adaptations suitable to overcome current niche limits is urgently needed to assess the resilience of species and ecosystems to human impact, including the challenges of global climate change.

Trophic specialization influences the rate of environmental niche evolution in damselfishes (Pomacentridae).

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Litsios, Glenn; Pellissier, Loïc; Forest, Félix; Lexer, Christian; Pearman, Peter B; Zimmermann, Niklaus E; Salamin, Nicolas

2012-09-22

The rate of environmental niche evolution describes the capability of species to explore the available environmental space and is known to vary among species owing to lineage-specific factors. Trophic specialization is a main force driving species evolution and is responsible for classical examples of adaptive radiations in fishes. We investigate the effect of trophic specialization on the rate of environmental niche evolution in the damselfish, Pomacentridae, which is an important family of tropical reef fishes. First, phylogenetic niche conservatism is not detected in the family using a standard test of phylogenetic signal, and we demonstrate that the environmental niches of damselfishes that differ in trophic specialization are not equivalent while they still overlap at their mean values. Second, we estimate the relative rates of niche evolution on the phylogenetic tree and show the heterogeneity among rates of environmental niche evolution of the three trophic groups. We suggest that behavioural characteristics related to trophic specialization can constrain the evolution of the environmental niche and lead to conserved niches in specialist lineages. Our results show the extent of influence of several traits on the evolution of the environmental niche and shed new light on the evolution of damselfishes, which is a key lineage in current efforts to conserve biodiversity in coral reefs.

Retinal Diseases Caused by Mutations in Genes Not Specifically Associated with the Clinical Diagnosis.

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Xia Wang

Full Text Available When seeking a confirmed molecular diagnosis in the research setting, patients with one descriptive diagnosis of retinal disease could carry pathogenic variants in genes not specifically associated with that description. However, this event has not been evaluated systematically in clinical diagnostic laboratories that validate fully all target genes to minimize false negatives/positives.We performed targeted next-generation sequencing analysis on 207 ocular disease-related genes for 42 patients whose DNA had been tested negative for disease-specific panels of genes known to be associated with retinitis pigmentosa, Leber congenital amaurosis, or exudative vitreoretinopathy.Pathogenic variants, including single nucleotide variations and copy number variations, were identified in 9 patients, including 6 with variants in syndromic retinal disease genes and 3 whose molecular diagnosis could not be distinguished easily from their submitted clinical diagnosis, accounting for 21% (9/42 of the unsolved cases.Our study underscores the clinical and genetic heterogeneity of retinal disorders and provides valuable reference to estimate the fraction of clinical samples whose retinal disorders could be explained by genes not specifically associated with the corresponding clinical diagnosis. Our data suggest that sequencing a larger set of retinal disorder related genes can increase the molecular diagnostic yield, especially for clinically hard-to-distinguish cases.

Microarray meta-analysis to explore abiotic stress-specific gene expression patterns in Arabidopsis.

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Shen, Po-Chih; Hour, Ai-Ling; Liu, Li-Yu Daisy

2017-12-01

Abiotic stresses are the major limiting factors that affect plant growth, development, yield and final quality. Deciphering the underlying mechanisms of plants' adaptations to stresses using few datasets might overlook the different aspects of stress tolerance in plants, which might be simultaneously and consequently operated in the system. Fortunately, the accumulated microarray expression data offer an opportunity to infer abiotic stress-specific gene expression patterns through meta-analysis. In this study, we propose to combine microarray gene expression data under control, cold, drought, heat, and salt conditions and determined modules (gene sets) of genes highly associated with each other according to the observed expression data. By analyzing the expression variations of the Eigen genes from different conditions, we had identified two, three, and five gene modules as cold-, heat-, and salt-specific modules, respectively. Most of the cold- or heat-specific modules were differentially expressed to a particular degree in shoot samples, while most of the salt-specific modules were differentially expressed to a particular degree in root samples. A gene ontology (GO) analysis on the stress-specific modules suggested that the gene modules exclusively enriched stress-related GO terms and that different genes under the same GO terms may be alternatively disturbed in different conditions. The gene regulatory events for two genes, DREB1A and DEAR1, in the cold-specific gene module had also been validated, as evidenced through the literature search. Our protocols study the specificity of the gene modules that were specifically activated under a particular type of abiotic stress. The biplot can also assist to visualize the stress-specific gene modules. In conclusion, our approach has the potential to further elucidate mechanisms in plants and beneficial for future experiments design under different abiotic stresses.

Ongoing niche differentiation under high gene flow in a polymorphic brackish water threespine stickleback (Gasterosteus aculeatus) population.

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Østbye, Kjartan; Taugbøl, Annette; Ravinet, Mark; Harrod, Chris; Pettersen, Ruben Alexander; Bernatchez, Louis; Vøllestad, Leif Asbjørn

2018-02-05

Marine threespine sticklebacks colonized and adapted to brackish and freshwater environments since the last Pleistocene glacial. Throughout the Holarctic, three lateral plate morphs are observed; the low, partial and completely plated morph. We test if the three plate morphs in the brackish water Lake Engervann, Norway, differ in body size, trophic morphology (gill raker number and length), niche (stable isotopes; δ 15 N, δ 13 C, and parasites (Theristina gasterostei, Trematoda spp.)), genetic structure (microsatellites) and the lateral-plate encoding Stn382 (Ectodysplasin) gene. We examine differences temporally (autumn 2006/spring 2007) and spatially (upper/lower sections of the lake - reflecting low versus high salinity). All morphs belonged to one gene pool. The complete morph was larger than the low plated, with the partial morph intermediate. The number of lateral plates ranged 8-71, with means of 64.2 for complete, 40.3 for partial, and 14.9 for low plated morph. Stickleback δ 15 N was higher in the lower lake section, while δ 13 C was higher in the upper section. Stickleback isotopic values were greater in autumn. The low plated morph had larger variances in δ 15 N and δ 13 C than the other morphs. Sticklebacks in the upper section had more T. gasterostei than in the lower section which had more Trematoda spp. Sticklebacks had less T. gasterostei, but more Trematoda spp. in autumn than spring. Sticklebacks with few and short rakers had more T. gasterostei, while sticklebacks with longer rakers had more Trematoda. spp. Stickleback with higher δ 15 N values had more T. gasterostei, while sticklebacks with higher δ 15 N and δ 13 C values had more Trematoda spp. The low plated morph had fewer Trematoda spp. than other morphs. Trait-ecology associations may imply that the three lateral plate morphs in the brackish water lagoon of Lake Engervann are experiencing ongoing divergent selection for niche and migratory life history strategies under high gene

Optimal structural inference of signaling pathways from unordered and overlapping gene sets.

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Acharya, Lipi R; Judeh, Thair; Wang, Guangdi; Zhu, Dongxiao

2012-02-15

A plethora of bioinformatics analysis has led to the discovery of numerous gene sets, which can be interpreted as discrete measurements emitted from latent signaling pathways. Their potential to infer signaling pathway structures, however, has not been sufficiently exploited. Existing methods accommodating discrete data do not explicitly consider signal cascading mechanisms that characterize a signaling pathway. Novel computational methods are thus needed to fully utilize gene sets and broaden the scope from focusing only on pairwise interactions to the more general cascading events in the inference of signaling pathway structures. We propose a gene set based simulated annealing (SA) algorithm for the reconstruction of signaling pathway structures. A signaling pathway structure is a directed graph containing up to a few hundred nodes and many overlapping signal cascades, where each cascade represents a chain of molecular interactions from the cell surface to the nucleus. Gene sets in our context refer to discrete sets of genes participating in signal cascades, the basic building blocks of a signaling pathway, with no prior information about gene orderings in the cascades. From a compendium of gene sets related to a pathway, SA aims to search for signal cascades that characterize the optimal signaling pathway structure. In the search process, the extent of overlap among signal cascades is used to measure the optimality of a structure. Throughout, we treat gene sets as random samples from a first-order Markov chain model. We evaluated the performance of SA in three case studies. In the first study conducted on 83 KEGG pathways, SA demonstrated a significantly better performance than Bayesian network methods. Since both SA and Bayesian network methods accommodate discrete data, use a 'search and score' network learning strategy and output a directed network, they can be compared in terms of performance and computational time. In the second study, we compared SA and

Beyond main effects of gene-sets: harsh parenting moderates the association between a dopamine gene-set and child externalizing behavior.

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Windhorst, Dafna A; Mileva-Seitz, Viara R; Rippe, Ralph C A; Tiemeier, Henning; Jaddoe, Vincent W V; Verhulst, Frank C; van IJzendoorn, Marinus H; Bakermans-Kranenburg, Marian J

2016-08-01

In a longitudinal cohort study, we investigated the interplay of harsh parenting and genetic variation across a set of functionally related dopamine genes, in association with children's externalizing behavior. This is one of the first studies to employ gene-based and gene-set approaches in tests of Gene by Environment (G × E) effects on complex behavior. This approach can offer an important alternative or complement to candidate gene and genome-wide environmental interaction (GWEI) studies in the search for genetic variation underlying individual differences in behavior. Genetic variants in 12 autosomal dopaminergic genes were available in an ethnically homogenous part of a population-based cohort. Harsh parenting was assessed with maternal (n = 1881) and paternal (n = 1710) reports at age 3. Externalizing behavior was assessed with the Child Behavior Checklist (CBCL) at age 5 (71 ± 3.7 months). We conducted gene-set analyses of the association between variation in dopaminergic genes and externalizing behavior, stratified for harsh parenting. The association was statistically significant or approached significance for children without harsh parenting experiences, but was absent in the group with harsh parenting. Similarly, significant associations between single genes and externalizing behavior were only found in the group without harsh parenting. Effect sizes in the groups with and without harsh parenting did not differ significantly. Gene-environment interaction tests were conducted for individual genetic variants, resulting in two significant interaction effects (rs1497023 and rs4922132) after correction for multiple testing. Our findings are suggestive of G × E interplay, with associations between dopamine genes and externalizing behavior present in children without harsh parenting, but not in children with harsh parenting experiences. Harsh parenting may overrule the role of genetic factors in externalizing behavior. Gene-based and gene-set

Exosomes as novel regulators of adult neurogenic niches

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Luis Federico Batiz

2016-01-01

Full Text Available Adult neurogenesis has been convincingly demonstrated in two regions of the mammalian brain: the sub-granular zone (SGZ of the dentate gyrus (DG in the hippocampus, and the sub-ventricular zone (SVZ of the lateral ventricles. SGZ newborn neurons are destined to the granular cell layer of the DG, while new neurons from the SVZ neurons migrate rostrally into the olfactory bulb. The process of adult neurogenesis persists throughout life and is supported by a pool of neural stem cells (NSCs, which reside in a unique and specialized microenvironment known as neurogenic niche. Neurogenic niches are structured by a complex organization of different cell types, including the NSC-neuron lineage, glial cells and vascular cells. Thus, cell-to-cell communication plays a key role in the dynamic modulation of homeostasis and plasticity of the adult neurogenic process. Specific cell-cell contacts and extracellular signals originated locally provide the necessary support and regulate the balance between self-renewal and differentiation of NSCs. Furthermore, extracellular signals originated at distant locations, including other brain regions or systemic organs, may reach the niche through the cerebrospinal fluid or the vasculature and influence its nature. The role of several secreted molecules, such as cytokines, growth factors, neurotransmitters, and hormones, in the biology of adult NSCs, has been systematically addressed. Interestingly, in addition to these well-recognized signals, a novel type of intercellular messengers has been identified recently: the extracellular vesicles (EVs. EVs, and particularly exosomes, are implicated in the transfer of mRNAs, microRNAs (miRNAs, proteins and lipids between cells and thus are able to modify the function of recipient cells. Exosomes appear to play a significant role in different stem cell niches such as the mesenchymal stem cell niche, cancer stem cell niche and pre-metastatic niche; however, their roles in adult

Intersexual trophic niche partitioning in an ant-eating spider (Araneae: Zodariidae.

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Stano Pekár

2011-01-01

Full Text Available Divergence in trophic niche between the sexes may function to reduce competition between the sexes ("intersexual niche partitioning hypothesis", or may be result from differential selection among the sexes on maximizing reproductive output ("sexual selection hypothesis". The latter may lead to higher energy demands in females driven by fecundity selection, while males invest in mate searching. We tested predictions of the two hypotheses underlying intersexual trophic niche partitioning in a natural population of spiders. Zodarion jozefienae spiders specialize on Messor barbarus ants that are polymorphic in body size and hence comprise potential trophic niches for the spider, making this system well-suited to study intersexual trophic niche partitioning.Comparative analysis of trophic morphology (the chelicerae and body size of males, females and juveniles demonstrated highly female biased SSD (Sexual Size Dimorphism in body size, body weight, and in the size of chelicerae, the latter arising from sex-specific growth patterns in trophic morphology. In the field, female spiders actively selected ant sub-castes that were larger than the average prey size, and larger than ants captured by juveniles and males. Female fecundity was highly positively correlated with female body mass, which reflects foraging success during the adult stage. Females in laboratory experiments preferred the large ant sub-castes and displayed higher capture efficiency. In contrast, males occupied a different trophic niche and showed reduced foraging effort and reduced prey capture and feeding efficiency compared with females and juveniles.Our data indicate that female-biased dimorphism in trophic morphology and body size correlate with sex-specific reproductive strategies. We propose that intersexual trophic niche partitioning is shaped primarily by fecundity selection in females, and results from sex-differences in the route to successful reproduction where females are

Within-population isotopic niche variability in savanna mammals: disparity between carnivores and herbivores

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Daryl eCodron

2016-02-01

Full Text Available Large mammal ecosystems have relatively simple food webs, usually comprising three – and sometimes only two – trophic links. Since many syntopic species from the same trophic level therefore share resources, dietary niche partitioning features prominently within these systems. In African and other subtropical savannas, stable carbon isotopes readily distinguish between herbivore species for which foliage and other parts of dicot plants (13C-depleted C3 vegetation are the primary resource (browsers and those for which grasses (13C-enriched C4 vegetation are staples (grazers. Similarly, carbon isotopes distinguish between carnivore diets that may be richer in either browser, grazer, or intermediate-feeding prey. Here, we investigate levels of carbon and nitrogen isotopic niche variation and niche partitioning within populations (or species of carnivores and herbivores from South African savannas. We emphasize predictable differences in within-population trends across trophic levels: we expect that herbivore populations, which require more foraging effort due to higher intake requirements, are far less likely to display within-population resource partitioning than carnivore populations. Our results reveal generally narrower isotopic niche breadths in herbivore than carnivore populations, but more importantly we find lower levels of isotopic differentiation across individuals within herbivore species. While these results offer some support for our general hypothesis, the current paucity of isotopic data for African carnivores limits our ability to test the complete set of predictions arising from our hypothesis. Nevertheless, given the different ecological and ecophysiological constraints to foraging behaviour within each trophic level, comparisons across carnivores and herbivores, which are possible within such simplified foodwebs, make these systems ideal for developing a process-based understanding of conditions underlying the evolution of

Grateful parents raising grateful children: Niche selection and the socialization of child gratitude.

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Rothenberg, William A; Hussong, Andrea M; Langley, Hillary A; Egerton, Gregory A; Halberstadt, Amy G; Coffman, Jennifer L; Mokrova, Irina; Costanzo, Philip R

2017-01-01

Given that children's exposure to gratitude-related activities may be one way that parents can socialize gratitude in their children, we examined whether parents' niche selection (i.e., tendency to choose perceived gratitude-inducing activities for their children) mediates the association between parents' reports of their own and their children's gratitude. Parent-child dyads ( N =101; children aged 6-9; 52% girls; 80% Caucasian; 85% mothers) participated in a laboratory visit and parents also completed a seven-day online diary regarding children's gratitude. Decomposing specific indirect effects within a structural equation model, we found that parents high in gratitude were more likely to set goals to use niche selection as a gratitude socialization strategy, and thereby more likely to place their children in gratitude-related activities. Placement in these activities, in turn, was associated with more frequent expression of gratitude in children. We describe future directions for research on parents' role in socializing gratitude in their children.

Evolutionary responses to a constructed niche: ancient Mesoamericans as a model of gene-culture coevolution.

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Tábita Hünemeier

Full Text Available Culture and genetics rely on two distinct but not isolated transmission systems. Cultural processes may change the human selective environment and thereby affect which individuals survive and reproduce. Here, we evaluated whether the modes of subsistence in Native American populations and the frequencies of the ABCA1*Arg230Cys polymorphism were correlated. Further, we examined whether the evolutionary consequences of the agriculturally constructed niche in Mesoamerica could be considered as a gene-culture coevolution model. For this purpose, we genotyped 229 individuals affiliated with 19 Native American populations and added data for 41 other Native American groups (n = 1905 to the analysis. In combination with the SNP cluster of a neutral region, this dataset was then used to unravel the scenario involved in 230Cys evolutionary history. The estimated age of 230Cys is compatible with its origin occurring in the American continent. The correlation of its frequencies with the archeological data on Zea pollen in Mesoamerica/Central America, the neutral coalescent simulations, and the F(ST-based natural selection analysis suggest that maize domestication was the driving force in the increase in the frequencies of 230Cys in this region. These results may represent the first example of a gene-culture coevolution involving an autochthonous American allele.

Tug of war in the haematopoietic stem cell niche: do myeloma plasma cells compete for the HSC niche?

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Noll, J E; Williams, S A; Purton, L E; Zannettino, A C W

2012-09-14

In the adult mammal, normal haematopoiesis occurs predominantly in the bone marrow, where primitive haematopoietic stem cells (HSC) and their progeny reside in specialised microenvironments. The bone marrow microenvironment contains specific anatomical areas (termed niches) that are highly specialised for the development of certain blood cell types, for example HSCs. The HSC niche provides important cell-cell interactions and signalling molecules that regulate HSC self-renewal and differentiation processes. These same signals and interactions are also important in the progression of haematological malignancies, such as multiple myeloma (MM). This review provides an overview of the bone marrow microenvironment and its involvement in normal, physiological HSC maintenance and plasma cell growth throughout MM disease progression.

Identifying niche-mediated regulatory factors of stem cell phenotypic state: a systems biology approach.

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Ravichandran, Srikanth; Del Sol, Antonio

2017-02-01

Understanding how the cellular niche controls the stem cell phenotype is often hampered due to the complexity of variegated niche composition, its dynamics, and nonlinear stem cell-niche interactions. Here, we propose a systems biology view that considers stem cell-niche interactions as a many-body problem amenable to simplification by the concept of mean field approximation. This enables approximation of the niche effect on stem cells as a constant field that induces sustained activation/inhibition of specific stem cell signaling pathways in all stem cells within heterogeneous populations exhibiting the same phenotype (niche determinants). This view offers a new basis for the development of single cell-based computational approaches for identifying niche determinants, which has potential applications in regenerative medicine and tissue engineering. © 2017 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

[Analysis of tissue-specific differentially methylated genes with differential gene expression in non-small cell lung cancer].

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Yin, L G; Zou, Z Q; Zhao, H Y; Zhang, C L; Shen, J G; Qi, L; Qi, M; Xue, Z Q

2014-01-01

Adenocarcinoma (ADC) and squamous cell carcinomas (SCC) are two subtypes of non-small cell lung carcinomas which are regarded as the leading cause of cancer-related malignancy worldwide. The aim of this study is to detect the differentially methylated loci (DMLs) and differentially methylated genes (DMGs) of these two tumor sets, and then to illustrate the different expression level of specific methylated genes. Using TCGA database and Illumina HumanMethylation 27 arrays, we first screened the DMGs and DMLs in tumor samples. Then, we explored the BiologicalProcess terms of hypermethylated and hypomethylated genes using Functional Gene Ontology (GO) catalogues. Hypermethylation intensively occurred in CpG-island, whereas hypomethylation was located in non-CpG-island. Most SCC and ADC hypermethylated genes involved GO function of DNA dependenit regulation of transcription, and hypomethylated genes mainly 'enriched in the term of immune responses. Additionally, the expression level of specific differentially methylated genesis distinctbetween ADC and SCC. It is concluded that ADC and SCC have different methylated status that might play an important role in carcinogenesis.

APPRIS 2017: principal isoforms for multiple gene sets

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Rodriguez-Rivas, Juan; Di Domenico, Tomás; Vázquez, Jesús; Valencia, Alfonso

2018-01-01

Abstract The APPRIS database (http://appris-tools.org) uses protein structural and functional features and information from cross-species conservation to annotate splice isoforms in protein-coding genes. APPRIS selects a single protein isoform, the ‘principal’ isoform, as the reference for each gene based on these annotations. A single main splice isoform reflects the biological reality for most protein coding genes and APPRIS principal isoforms are the best predictors of these main proteins isoforms. Here, we present the updates to the database, new developments that include the addition of three new species (chimpanzee, Drosophila melangaster and Caenorhabditis elegans), the expansion of APPRIS to cover the RefSeq gene set and the UniProtKB proteome for six species and refinements in the core methods that make up the annotation pipeline. In addition APPRIS now provides a measure of reliability for individual principal isoforms and updates with each release of the GENCODE/Ensembl and RefSeq reference sets. The individual GENCODE/Ensembl, RefSeq and UniProtKB reference gene sets for six organisms have been merged to produce common sets of splice variants. PMID:29069475

Toxin-antitoxin systems are important for niche-specific colonization and stress resistance of uropathogenic Escherichia coli.

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J Paul Norton

Full Text Available Toxin-antitoxin (TA systems are prevalent in many bacterial genomes and have been implicated in biofilm and persister cell formation, but the contribution of individual chromosomally encoded TA systems during bacterial pathogenesis is not well understood. Of the known TA systems encoded by Escherichia coli, only a subset is associated with strains of extraintestinal pathogenic E. coli (ExPEC. These pathogens colonize diverse niches and are a major cause of sepsis, meningitis, and urinary tract infections. Using a murine infection model, we show that two TA systems (YefM-YoeB and YbaJ-Hha independently promote colonization of the bladder by the reference uropathogenic ExPEC isolate CFT073, while a third TA system comprised of the toxin PasT and the antitoxin PasI is critical to ExPEC survival within the kidneys. The PasTI TA system also enhances ExPEC persister cell formation in the presence of antibiotics and markedly increases pathogen resistance to nutrient limitation as well as oxidative and nitrosative stresses. On its own, low-level expression of PasT protects ExPEC from these stresses, whereas overexpression of PasT is toxic and causes bacterial stasis. PasT-induced stasis can be rescued by overexpression of PasI, indicating that PasTI is a bona fide TA system. By mutagenesis, we find that the stress resistance and toxic effects of PasT can be uncoupled and mapped to distinct domains. Toxicity was specifically linked to sequences within the N-terminus of PasT, a region that also promotes the development of persister cells. These results indicate discrete, multipurpose functions for a TA-associated toxin and demonstrate that individual TA systems can provide bacteria with pronounced fitness advantages dependent on toxin expression levels and the specific environmental niche occupied.

Can survival prediction be improved by merging gene expression data sets?

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Haleh Yasrebi

Full Text Available BACKGROUND: High-throughput gene expression profiling technologies generating a wealth of data, are increasingly used for characterization of tumor biopsies for clinical trials. By applying machine learning algorithms to such clinically documented data sets, one hopes to improve tumor diagnosis, prognosis, as well as prediction of treatment response. However, the limited number of patients enrolled in a single trial study limits the power of machine learning approaches due to over-fitting. One could partially overcome this limitation by merging data from different studies. Nevertheless, such data sets differ from each other with regard to technical biases, patient selection criteria and follow-up treatment. It is therefore not clear at all whether the advantage of increased sample size outweighs the disadvantage of higher heterogeneity of merged data sets. Here, we present a systematic study to answer this question specifically for breast cancer data sets. We use survival prediction based on Cox regression as an assay to measure the added value of merged data sets. RESULTS: Using time-dependent Receiver Operating Characteristic-Area Under the Curve (ROC-AUC and hazard ratio as performance measures, we see in overall no significant improvement or deterioration of survival prediction with merged data sets as compared to individual data sets. This apparently was due to the fact that a few genes with strong prognostic power were not available on all microarray platforms and thus were not retained in the merged data sets. Surprisingly, we found that the overall best performance was achieved with a single-gene predictor consisting of CYB5D1. CONCLUSIONS: Merging did not deteriorate performance on average despite (a The diversity of microarray platforms used. (b The heterogeneity of patients cohorts. (c The heterogeneity of breast cancer disease. (d Substantial variation of time to death or relapse. (e The reduced number of genes in the merged data

Evolutionary origins of Brassicaceae specific genes in Arabidopsis thaliana

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2011-01-01

Background All sequenced genomes contain a proportion of lineage-specific genes, which exhibit no sequence similarity to any genes outside the lineage. Despite their prevalence, the origins and functions of most lineage-specific genes remain largely unknown. As more genomes are sequenced opportunities for understanding evolutionary origins and functions of lineage-specific genes are increasing. Results This study provides a comprehensive analysis of the origins of lineage-specific genes (LSGs) in Arabidopsis thaliana that are restricted to the Brassicaceae family. In this study, lineage-specific genes within the nuclear (1761 genes) and mitochondrial (28 genes) genomes are identified. The evolutionary origins of two thirds of the lineage-specific genes within the Arabidopsis thaliana genome are also identified. Almost a quarter of lineage-specific genes originate from non-lineage-specific paralogs, while the origins of ~10% of lineage-specific genes are partly derived from DNA exapted from transposable elements (twice the proportion observed for non-lineage-specific genes). Lineage-specific genes are also enriched in genes that have overlapping CDS, which is consistent with such novel genes arising from overprinting. Over half of the subset of the 958 lineage-specific genes found only in Arabidopsis thaliana have alignments to intergenic regions in Arabidopsis lyrata, consistent with either de novo origination or differential gene loss and retention, with both evolutionary scenarios explaining the lineage-specific status of these genes. A smaller number of lineage-specific genes with an incomplete open reading frame across different Arabidopsis thaliana accessions are further identified as accession-specific genes, most likely of recent origin in Arabidopsis thaliana. Putative de novo origination for two of the Arabidopsis thaliana-only genes is identified via additional sequencing across accessions of Arabidopsis thaliana and closely related sister species

Interactions between structural and chemical biomimetism in synthetic stem cell niches

International Nuclear Information System (INIS)

Nava, Michele M; Raimondi, Manuela T; Credi, Caterina; De Marco, Carmela; Turri, Stefano; Cerullo, Giulio; Osellame, Roberto

2015-01-01

Advancements in understanding stem cell functions and differentiation are of key importance for the clinical success of stem-cell-based therapies. 3D structural niches fabricated by two-photon polymerization are a powerful platform for controlling stem cell growth and differentiation. In this paper, we investigate the possibility of further controlling stem cell fate by tuning the mechanical properties of such niches through coating with thin layers of biomimetic hyaluronan-based and gelatin-based hydrogels. We first assess the biocompatibility of chemical coatings and then study the interactions between structural and chemical biomimetism on the response of MSCs in terms of proliferation and differentiation. We observed a clear effect of the hydrogel coating on otherwise identical 3D scaffolds. In particular, in gelatin-coated niches we observed a stronger metabolic activity and commitment toward the osteo-chondral lineage with respect to hyaluronan-coated niches. Conversely, a reduction in the homing effect was observed in all the coated niches, especially in gelatin-coated niches. This study demonstrates the feasibility of controlling independently different mechanical cues, in bioengineered stem cell niches, i.e. the 3D scaffold geometry and the surface stiffness. This will allow, on the one hand, understanding their specific role in stem cell proliferation and differentiation and, on the other hand, finely tuning their synergistic effect. (paper)

Niche energy markets in rural areas

International Nuclear Information System (INIS)

Walsh, M.; McCarthy, S.

1996-01-01

The objective of this project is the development of a standard methodology for integrating non-food crops in rural areas with niche energy markets. This has involved a number of steps including (i) identification of 3 niche markets for energy crops which are of common interest to the partners, (ii) application of the standard costing methodology to investigate these three niche markets and (iii) comparison of the results from this work in three workshops (one for each market). Three tightly defined niche markets were identified; these were chosen following an examination of the national energy marekts in each of the partners countries (Ireland, Germany, Netherlands, UK, Greece and Portugal). This paper gives an overview of the national energy markets which were examined. The three niche markets are introduced and the reasons for their selection given. The application of the methodology to each of the niche markets is presented along with the conclusions of the partners regarding the niche markets. (Author)

Stem cell autotomy and niche interaction in different systems.

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Dorn, David C; Dorn, August

2015-07-26

pruning and dying-back degeneration in neurodegenerative diseases. Especially the hypothesis of an existing evolutionary conserved "autodestruction program" in axons that might also be active in GSC projections appears attractive. Investigations on the underlying signaling pathways have to be carried out. There are two other well known cases of programmed cell autotomy: the enucleation of erythroblasts in the process of erythrocyte maturation and the segregation of thousands of thrombocytes (platelets) from one megakaryocyte. Both progenitor cell types - erythroblasts and megakaryocytes - are associated with a niche in the bone marrow, erythroblasts with a macrophage, which they surround, and the megakaryocytes with the endothelial cells of sinusoids and their extracellular matrix. Although the regulatory mechanisms may be specific in each case, there is one aspect that connects all described processes of programmed cell autotomy and neuronal autodestruction: apoptotic pathways play always a prominent role. Studies on the role of male GSC autotomy in stem cell-niche interaction have just started but are expected to reveal hitherto unknown ways of signal exchange. Spermatogenesis in mammals advance our understanding of insect spermatogenesis. Mammal and insect spermatogenesis share some broad principles, but a comparison of the signaling pathways is difficult. We have intimate knowledge from Drosophila, but of almost no other insect, and we have only limited knowledge from mammals. The discovery of stem cell autotomy as part of the interaction with the niche promises new general insights into the complicated stem cell-niche interdependence.

Stem cell autotomy and niche interaction in different systems

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Dorn, David C; Dorn, August

2015-01-01

pruning and dying-back degeneration in neurodegenerative diseases. Especially the hypothesis of an existing evolutionary conserved “autodestruction program” in axons that might also be active in GSC projections appears attractive. Investigations on the underlying signaling pathways have to be carried out. There are two other well known cases of programmed cell autotomy: the enucleation of erythroblasts in the process of erythrocyte maturation and the segregation of thousands of thrombocytes (platelets) from one megakaryocyte. Both progenitor cell types - erythroblasts and megakaryocytes - are associated with a niche in the bone marrow, erythroblasts with a macrophage, which they surround, and the megakaryocytes with the endothelial cells of sinusoids and their extracellular matrix. Although the regulatory mechanisms may be specific in each case, there is one aspect that connects all described processes of programmed cell autotomy and neuronal autodestruction: apoptotic pathways play always a prominent role. Studies on the role of male GSC autotomy in stem cell-niche interaction have just started but are expected to reveal hitherto unknown ways of signal exchange. Spermatogenesis in mammals advance our understanding of insect spermatogenesis. Mammal and insect spermatogenesis share some broad principles, but a comparison of the signaling pathways is difficult. We have intimate knowledge from Drosophila, but of almost no other insect, and we have only limited knowledge from mammals. The discovery of stem cell autotomy as part of the interaction with the niche promises new general insights into the complicated stem cell-niche interdependence. PMID:26240680

The human and murine hematopoietic stem cell niches: are they comparable?

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van Pel, Melissa; Fibbe, Willem E; Schepers, Koen

2016-04-01

Hematopoietic stem cells (HSCs) reside in specific niches that provide various instructive cues that regulate HSC self-renewal and their development into all mature cells of the peripheral blood. Progress in this research field has largely been guided by mouse studies. However, parallel studies with human subjects, tissues, and cells, in combination with xenotransplantation experiments in immunodeficient mice, have contributed to our increased understanding of the human HSC niche. Here, we summarize our current knowledge of the various specialized subsets of both stromal and hematopoietic cells that support HSCs through cell-cell interactions and secreted factors, and the many parallels between the murine and human HSC niches. Furthermore, we discuss recent technological advances that are likely to improve our understanding of the human HSC niche, a better understanding of which may allow further identification of unique molecular and cellular pathways in the HSC niche. This information may help to further improve the outcome of HSC transplantation and refine the treatment of hematopoietic diseases. © 2015 New York Academy of Sciences.

Niche players

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Seandel, Marco; Falciatori, Ilaria; Shmelkov, Sergey V.; Kim, Jiyeon; James, Daylon; Rafii, Shahin

2010-01-01

The undifferentiated spermatogonia of adult mouse testes are composed of both true stem cells and committed progenitors. It is unclear what normally prevents these adult germ cells from manifesting multipotency. The critical elements of the spermatogonial stem cell niche, while poorly understood, are thought to be composed of Sertoli cells with several other somatic cell types in close proximity. We recently discovered a novel orphan G-protein coupled receptor (GPR125) that is restricted to undifferentiated spermatogonia within the testis. GPR125 expression was maintained when the progenitor cells were extracted from the in vivo niche and propagated under growth conditions that recapitulate key elements of the niche. Such conditions preserved the ability of the cells to generate multipotent derivatives, known as multipotent adult spermatogonial derived progenitor cells (MASCs). Upon differentiation, the latter produced a variety tissues including functional endothelium, illustrating the potential applications of such cells. Thus, GPR125 represents a novel target for purifying adult stem and progenitors from tissues, with the goal of developing autologous multipotent cell lines. PMID:18256534

Comparative study on gene set and pathway topology-based enrichment methods.

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Bayerlová, Michaela; Jung, Klaus; Kramer, Frank; Klemm, Florian; Bleckmann, Annalen; Beißbarth, Tim

2015-10-22

Enrichment analysis is a popular approach to identify pathways or sets of genes which are significantly enriched in the context of differentially expressed genes. The traditional gene set enrichment approach considers a pathway as a simple gene list disregarding any knowledge of gene or protein interactions. In contrast, the new group of so called pathway topology-based methods integrates the topological structure of a pathway into the analysis. We comparatively investigated gene set and pathway topology-based enrichment approaches, considering three gene set and four topological methods. These methods were compared in two extensive simulation studies and on a benchmark of 36 real datasets, providing the same pathway input data for all methods. In the benchmark data analysis both types of methods showed a comparable ability to detect enriched pathways. The first simulation study was conducted with KEGG pathways, which showed considerable gene overlaps between each other. In this study with original KEGG pathways, none of the topology-based methods outperformed the gene set approach. Therefore, a second simulation study was performed on non-overlapping pathways created by unique gene IDs. Here, methods accounting for pathway topology reached higher accuracy than the gene set methods, however their sensitivity was lower. We conducted one of the first comprehensive comparative works on evaluating gene set against pathway topology-based enrichment methods. The topological methods showed better performance in the simulation scenarios with non-overlapping pathways, however, they were not conclusively better in the other scenarios. This suggests that simple gene set approach might be sufficient to detect an enriched pathway under realistic circumstances. Nevertheless, more extensive studies and further benchmark data are needed to systematically evaluate these methods and to assess what gain and cost pathway topology information introduces into enrichment analysis. Both

Niche evolution and adaptive radiation: Testing the order of trait divergence

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Ackerly, D.D.; Schwilk, D.W.; Webb, C.O.

2006-01-01

In the course of an adaptive radiation, the evolution of niche parameters is of particular interest for understanding modes of speciation and the consequences for coexistence of related species within communities. We pose a general question: In the course of an evolutionary radiation, do traits related to within-community niche differences (?? niche) evolve before or after differentiation of macrohabitat affinity or climatic tolerances (?? niche)? Here we introduce a new test to address this question, based on a modification of the method of independent contrasts. The divergence order test (DOT) is based on the average age of the nodes on a tree, weighted by the absolute magnitude of the contrast at each node for a particular trait. The comparison of these weighted averages reveals whether large divergences for one trait have occurred earlier or later in the course of diversification, relative to a second trait; significance is determined by bootstrapping from maximum-likelihood ancestral state reconstructions. The method is applied to the evolution of Ceanothus, a woody plant group in California, in which co-occurring species exhibit significant differences in a key leaf trait (specific leaf area) associated with contrasting physiological and life history strategies. Co-occurring species differ more for this trait than expected under a null model of community assembly. This ?? niche difference evolved early in the divergence of two major subclades within Ceanothus, whereas climatic distributions (?? niche traits) diversified later within each of the subclades. However, rapid evolution of climate parameters makes inferences of early divergence events highly uncertain, and differentiation of the ?? niche might have taken place throughout the evolution of the group, without leaving a clear phylogenetic signal. Similar patterns observed in several plant and animal groups suggest that early divergence of ?? niche traits might be a common feature of niche evolution in

LEGO: a novel method for gene set over-representation analysis by incorporating network-based gene weights.

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Dong, Xinran; Hao, Yun; Wang, Xiao; Tian, Weidong

2016-01-11

Pathway or gene set over-representation analysis (ORA) has become a routine task in functional genomics studies. However, currently widely used ORA tools employ statistical methods such as Fisher's exact test that reduce a pathway into a list of genes, ignoring the constitutive functional non-equivalent roles of genes and the complex gene-gene interactions. Here, we develop a novel method named LEGO (functional Link Enrichment of Gene Ontology or gene sets) that takes into consideration these two types of information by incorporating network-based gene weights in ORA analysis. In three benchmarks, LEGO achieves better performance than Fisher and three other network-based methods. To further evaluate LEGO's usefulness, we compare LEGO with five gene expression-based and three pathway topology-based methods using a benchmark of 34 disease gene expression datasets compiled by a recent publication, and show that LEGO is among the top-ranked methods in terms of both sensitivity and prioritization for detecting target KEGG pathways. In addition, we develop a cluster-and-filter approach to reduce the redundancy among the enriched gene sets, making the results more interpretable to biologists. Finally, we apply LEGO to two lists of autism genes, and identify relevant gene sets to autism that could not be found by Fisher.

Identification of a set of genes showing regionally enriched expression in the mouse brain

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Marra Marco A

2008-07-01

Full Text Available Abstract Background The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters ( Results We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Conclusion Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression.

Advances and Limitations of Disease Biogeography Using Ecological Niche Modeling.

Science.gov (United States)

Escobar, Luis E; Craft, Meggan E

2016-01-01

Mapping disease transmission risk is crucial in public and animal health for evidence based decision-making. Ecology and epidemiology are highly related disciplines that may contribute to improvements in mapping disease, which can be used to answer health related questions. Ecological niche modeling is increasingly used for understanding the biogeography of diseases in plants, animals, and humans. However, epidemiological applications of niche modeling approaches for disease mapping can fail to generate robust study designs, producing incomplete or incorrect inferences. This manuscript is an overview of the history and conceptual bases behind ecological niche modeling, specifically as applied to epidemiology and public health; it does not pretend to be an exhaustive and detailed description of ecological niche modeling literature and methods. Instead, this review includes selected state-of-the-science approaches and tools, providing a short guide to designing studies incorporating information on the type and quality of the input data (i.e., occurrences and environmental variables), identification and justification of the extent of the study area, and encourages users to explore and test diverse algorithms for more informed conclusions. We provide a friendly introduction to the field of disease biogeography presenting an updated guide for researchers looking to use ecological niche modeling for disease mapping. We anticipate that ecological niche modeling will soon be a critical tool for epidemiologists aiming to map disease transmission risk, forecast disease distribution under climate change scenarios, and identify landscape factors triggering outbreaks.

Time-specific ecological niche modeling predicts spatial dynamics of vector insects and human dengue cases.

Science.gov (United States)

Peterson, A Townsend; Martínez-Campos, Carmen; Nakazawa, Yoshinori; Martínez-Meyer, Enrique

2005-09-01

Numerous human diseases-malaria, dengue, yellow fever and leishmaniasis, to name a few-are transmitted by insect vectors with brief life cycles and biting activity that varies in both space and time. Although the general geographic distributions of these epidemiologically important species are known, the spatiotemporal variation in their emergence and activity remains poorly understood. We used ecological niche modeling via a genetic algorithm to produce time-specific predictive models of monthly distributions of Aedes aegypti in Mexico in 1995. Significant predictions of monthly mosquito activity and distributions indicate that predicting spatiotemporal dynamics of disease vector species is feasible; significant coincidence with human cases of dengue indicate that these dynamics probably translate directly into transmission of dengue virus to humans. This approach provides new potential for optimizing use of resources for disease prevention and remediation via automated forecasting of disease transmission risk.

Niche construction game cancer cells play.

Science.gov (United States)

Bergman, Aviv; Gligorijevic, Bojana

2015-10-01

Niche construction concept was originally defined in evolutionary biology as the continuous interplay between natural selection via environmental conditions and the modification of these conditions by the organism itself. Processes unraveling during cancer metastasis include construction of niches, which cancer cells use towards more efficient survival, transport into new environments and preparation of the remote sites for their arrival. Many elegant experiments were done lately illustrating, for example, the premetastatic niche construction, but there is practically no mathematical modeling done which would apply the niche construction framework. To create models useful for understanding niche construction role in cancer progression, we argue that a) genetic, b) phenotypic and c) ecological levels are to be included. While the model proposed here is phenomenological in its current form, it can be converted into a predictive outcome model via experimental measurement of the model parameters. Here we give an overview of an experimentally formulated problem in cancer metastasis and propose how niche construction framework can be utilized and broadened to model it. Other life science disciplines, such as host-parasite coevolution, may also benefit from niche construction framework adaptation, to satisfy growing need for theoretical considerations of data collected by experimental biology.

Niche construction game cancer cells play

Science.gov (United States)

Bergman, Aviv; Gligorijevic, Bojana

2015-10-01

Niche construction concept was originally defined in evolutionary biology as the continuous interplay between natural selection via environmental conditions and the modification of these conditions by the organism itself. Processes unraveling during cancer metastasis include construction of niches, which cancer cells use towards more efficient survival, transport into new environments and preparation of the remote sites for their arrival. Many elegant experiments were done lately illustrating, for example, the premetastatic niche construction, but there is practically no mathematical modeling done which would apply the niche construction framework. To create models useful for understanding niche construction role in cancer progression, we argue that a) genetic, b) phenotypic and c) ecological levels are to be included. While the model proposed here is phenomenological in its current form, it can be converted into a predictive outcome model via experimental measurement of the model parameters. Here we give an overview of an experimentally formulated problem in cancer metastasis and propose how niche construction framework can be utilized and broadened to model it. Other life science disciplines, such as host-parasite coevolution, may also benefit from niche construction framework adaptation, to satisfy growing need for theoretical considerations of data collected by experimental biology.

Spatial distributions of niche-constructing populations

Directory of Open Access Journals (Sweden)

Xiaozhuo Han

2015-12-01

Full Text Available Niche construction theory regards organisms not only as the object of natural selection but also an active subject that can change their own selective pressure through eco-evolutionary feedbacks. Through reviewing the existing works on the theoretical models of niche construction, here we present the progress made on how niche construction influences genetic structure of spatially structured populations and the spatial-temporal dynamics of metapopulations, with special focuses on mathematical models and simulation methods. The majority of results confirmed that niche construction can significantly alter the evolutionary trajectories of structured populations. Organism-environmental interactions induced by niche construction can have profound influence on the dynamics, competition and diversity of metapopulations. It can affect fine-scale spatially distribution of species and spatial heterogeneity of the environment. We further propose a few research directions with potentials, such as applying adaptive dynamics or spatial game theory to explore the effect of niche construction on phenotypic evolution and diversification.

Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans.

Science.gov (United States)

Gottlieb, Assaf; Daneshjou, Roxana; DeGorter, Marianne; Bourgeois, Stephane; Svensson, Peter J; Wadelius, Mia; Deloukas, Panos; Montgomery, Stephen B; Altman, Russ B

2017-11-24

Genome-wide association studies are useful for discovering genotype-phenotype associations but are limited because they require large cohorts to identify a signal, which can be population-specific. Mapping genetic variation to genes improves power and allows the effects of both protein-coding variation as well as variation in expression to be combined into "gene level" effects. Previous work has shown that warfarin dose can be predicted using information from genetic variation that affects protein-coding regions. Here, we introduce a method that improves dose prediction by integrating tissue-specific gene expression. In particular, we use drug pathways and expression quantitative trait loci knowledge to impute gene expression-on the assumption that differential expression of key pathway genes may impact dose requirement. We focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of warfarin within training and validation sets comprising both European and African-descent individuals. We build gene-tissue signatures associated with warfarin dose in a cohort-specific manner and identify a signature of 11 gene-tissue pairs that significantly augments the International Warfarin Pharmacogenetics Consortium dosage-prediction algorithm in both populations. Our results demonstrate that imputed expression can improve dose prediction and bridge population-specific compositions. MATLAB code is available at https://github.com/assafgo/warfarin-cohort.

Gene set analysis: limitations in popular existing methods and proposed improvements.

Science.gov (United States)

Mishra, Pashupati; Törönen, Petri; Leino, Yrjö; Holm, Liisa

2014-10-01

Gene set analysis is the analysis of a set of genes that collectively contribute to a biological process. Most popular gene set analysis methods are based on empirical P-value that requires large number of permutations. Despite numerous gene set analysis methods developed in the past decade, the most popular methods still suffer from serious limitations. We present a gene set analysis method (mGSZ) based on Gene Set Z-scoring function (GSZ) and asymptotic P-values. Asymptotic P-value calculation requires fewer permutations, and thus speeds up the gene set analysis process. We compare the GSZ-scoring function with seven popular gene set scoring functions and show that GSZ stands out as the best scoring function. In addition, we show improved performance of the GSA method when the max-mean statistics is replaced by the GSZ scoring function. We demonstrate the importance of both gene and sample permutations by showing the consequences in the absence of one or the other. A comparison of asymptotic and empirical methods of P-value estimation demonstrates a clear advantage of asymptotic P-value over empirical P-value. We show that mGSZ outperforms the state-of-the-art methods based on two different evaluations. We compared mGSZ results with permutation and rotation tests and show that rotation does not improve our asymptotic P-values. We also propose well-known asymptotic distribution models for three of the compared methods. mGSZ is available as R package from cran.r-project.org. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The multi-niche crowding genetic algorithm: Analysis and applications

Energy Technology Data Exchange (ETDEWEB)

Cedeno, Walter [Univ. of California, Davis, CA (United States)

1995-09-01

The ability of organisms to evolve and adapt to the environment has provided mother nature with a rich and diverse set of species. Only organisms well adapted to their environment can survive from one generation to the next, transferring on the traits, that made them successful, to their offspring. Competition for resources and the ever changing environment drives some species to extinction and at the same time others evolve to maintain the delicate balance in nature. In this disertation we present the multi-niche crowding genetic algorithm, a computational metaphor to the survival of species in ecological niches in the face of competition. The multi-niche crowding genetic algorithm maintains stable subpopulations of solutions in multiple niches in multimodal landscapes. The algorithm introduces the concept of crowding selection to promote mating among members with qirnilar traits while allowing many members of the population to participate in mating. The algorithm uses worst among most similar replacement policy to promote competition among members with similar traits while allowing competition among members of different niches as well. We present empirical and theoretical results for the success of the multiniche crowding genetic algorithm for multimodal function optimization. The properties of the algorithm using different parameters are examined. We test the performance of the algorithm on problems of DNA Mapping, Aquifer Management, and the File Design Problem. Applications that combine the use of heuristics and special operators to solve problems in the areas of combinatorial optimization, grouping, and multi-objective optimization. We conclude by presenting the advantages and disadvantages of the algorithm and describing avenues for future investigation to answer other questions raised by this study.

The influence of social niche on cultural niche construction: modelling changes in belief about marriage form in Taiwan

Science.gov (United States)

Lipatov, Mikhail; Brown, Melissa J.; Feldman, Marcus W.

2011-01-01

With introduction of social niche effects into a model of cultural change, the frequency of a practice cannot predict the frequency of its underlying belief. The combination of a general model with empirical data from a specific case illustrates the importance of collaboration between modellers and field researchers, and identifies the type of quantitative data necessary for analysing case studies. Demographic data from colonial-period household registers in Taiwan document a shift in marriage form within 40 years, from a mixture of uxorilocal marriages and virilocal marriages to the latter's dominance. Ethnographic data indicate marriage-related beliefs, costs, ethnic effects and colonial policies as well as the importance of horizontal cultural transmission. We present a formal model for the effects of moral beliefs about marriage and a population economic index on the decline of uxorilocal marriage. We integrate empirical marriage rates and an estimated economic index to produce five projections of the historical frequencies of one belief. These projections demonstrate how economic development may affect a cultural niche. They also indicate the need for future research on the relationship between wealth and cultural variability, the motivational force of cultural versus social factors, and the process of cultural niche construction. PMID:21320903

Niches for the Long-Term Maintenance of Tissue-Resident Memory T Cells

Science.gov (United States)

Takamura, Shiki

2018-01-01

Tissue-resident memory T cells (TRM cells) are a population of immune cells that reside in the lymphoid and non-lymphoid organs without recirculation through the blood. These important cells occupy and utilize unique anatomical and physiological niches that are distinct from those for other memory T cell populations, such as central memory T cells in the secondary lymphoid organs and effector memory T cells that circulate through the tissues. CD8+ TRM cells typically localize in the epithelial layers of barrier tissues where they are optimally positioned to act as sentinels to trigger antigen-specific protection against reinfection. CD4+ TRM cells typically localize below the epithelial layers, such as below the basement membrane, and cluster in lymphoid structures designed to optimize interactions with antigen-presenting cells upon reinfection. A key feature of TRM populations is their ability to be maintained in barrier tissues for prolonged periods of time. For example, skin CD8+ TRM cells displace epidermal niches originally occupied by γδ T cells, thereby enabling their stable persistence for years. It is also clear that the long-term maintenance of TRM cells in different microenvironments is dependent on multiple tissue-specific survival cues, although the specific details are poorly understood. However, not all TRM persist over the long term. Recently, we identified a new spatial niche for the maintenance of CD8+ TRM cells in the lung, which is created at the site of tissue regeneration after injury [termed repair-associated memory depots (RAMD)]. The short-lived nature of RAMD potentially explains the short lifespans of CD8+ TRM cells in this particular tissue. Clearly, a better understanding of the niche-dependent maintenance of TRM cells will be important for the development of vaccines designed to promote barrier immunity. In this review, we discuss recent advances in our understanding of the properties and nature of tissue-specific niches that

ECRB ALCOVE AND NICHE GROUND SUPPORT ANALYSIS

International Nuclear Information System (INIS)

J.W. Keifer

1999-01-01

The purpose of the analysis is to provide design bases for Enhanced Characterization of the Repository Block (ECRB) alcove and niche ground support drawings. The objective is to evaluate the ESF Alcove Ground Support Analysis (Ref 5.1) to determine if the calculations technically bound the ECRB alcoves and to address specific differences in the conditions and constraints

Beyond main effects of gene-sets: harsh parenting moderates the association between a dopamine gene-set and child externalizing behavior

NARCIS (Netherlands)

J. Windhorst (Judith); V. Mileva-Seitz (Viara); R.C.A. Rippe (Ralph C.A.); H.W. Tiemeier (Henning); V.W.V. Jaddoe (Vincent); F.C. Verhulst (Frank); M.H. van IJzendoorn (Rien); M.J. Bakermans-Kranenburg (Marian)

2016-01-01

textabstractBackground: In a longitudinal cohort study, we investigated the interplay of harsh parenting and genetic variation across a set of functionally related dopamine genes, in association with children's externalizing behavior. This is one of the first studies to employ gene-based and

Mammalian transcriptional hotspots are enriched for tissue specific enhancers near cell type specific highly expressed genes and are predicted to act as transcriptional activator hubs.

Science.gov (United States)

Joshi, Anagha

2014-12-30

Transcriptional hotspots are defined as genomic regions bound by multiple factors. They have been identified recently as cell type specific enhancers regulating developmentally essential genes in many species such as worm, fly and humans. The in-depth analysis of hotspots across multiple cell types in same species still remains to be explored and can bring new biological insights. We therefore collected 108 transcription-related factor (TF) ChIP sequencing data sets in ten murine cell types and classified the peaks in each cell type in three groups according to binding occupancy as singletons (low-occupancy), combinatorials (mid-occupancy) and hotspots (high-occupancy). The peaks in the three groups clustered largely according to the occupancy, suggesting priming of genomic loci for mid occupancy irrespective of cell type. We then characterized hotspots for diverse structural functional properties. The genes neighbouring hotspots had a small overlap with hotspot genes in other cell types and were highly enriched for cell type specific function. Hotspots were enriched for sequence motifs of key TFs in that cell type and more than 90% of hotspots were occupied by pioneering factors. Though we did not find any sequence signature in the three groups, the H3K4me1 binding profile had bimodal peaks at hotspots, distinguishing hotspots from mono-modal H3K4me1 singletons. In ES cells, differentially expressed genes after perturbation of activators were enriched for hotspot genes suggesting hotspots primarily act as transcriptional activator hubs. Finally, we proposed that ES hotspots might be under control of SetDB1 and not DNMT for silencing. Transcriptional hotspots are enriched for tissue specific enhancers near cell type specific highly expressed genes. In ES cells, they are predicted to act as transcriptional activator hubs and might be under SetDB1 control for silencing.

Tracking niche variation over millennial timescales in sympatric killer whale lineages.

Science.gov (United States)

Foote, Andrew D; Newton, Jason; Ávila-Arcos, María C; Kampmann, Marie-Louise; Samaniego, Jose A; Post, Klaas; Rosing-Asvid, Aqqalu; Sinding, Mikkel-Holger S; Gilbert, M Thomas P

2013-10-07

Niche variation owing to individual differences in ecology has been hypothesized to be an early stage of sympatric speciation. Yet to date, no study has tracked niche width over more than a few generations. In this study, we show the presence of isotopic niche variation over millennial timescales and investigate the evolutionary outcomes. Isotopic ratios were measured from tissue samples of sympatric killer whale Orcinus orca lineages from the North Sea, spanning over 10 000 years. Isotopic ratios spanned a range similar to the difference in isotopic values of two known prey items, herring Clupea harengus and harbour seal Phoca vitulina. Two proxies of the stage of speciation, lineage sorting of mitogenomes and genotypic clustering, were both weak to intermediate indicating that speciation has made little progress. Thus, our study confirms that even with the necessary ecological conditions, i.e. among-individual variation in ecology, it is difficult for sympatric speciation to progress in the face of gene flow. In contrast to some theoretical models, our empirical results suggest that sympatric speciation driven by among-individual differences in ecological niche is a slow process and may not reach completion. We argue that sympatric speciation is constrained in this system owing to the plastic nature of the behavioural traits under selection when hunting either mammals or fish.

A variational approach to niche construction.

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Constant, Axel; Ramstead, Maxwell J D; Veissière, Samuel P L; Campbell, John O; Friston, Karl J

2018-04-01

In evolutionary biology, niche construction is sometimes described as a genuine evolutionary process whereby organisms, through their activities and regulatory mechanisms, modify their environment such as to steer their own evolutionary trajectory, and that of other species. There is ongoing debate, however, on the extent to which niche construction ought to be considered a bona fide evolutionary force, on a par with natural selection. Recent formulations of the variational free-energy principle as applied to the life sciences describe the properties of living systems, and their selection in evolution, in terms of variational inference. We argue that niche construction can be described using a variational approach. We propose new arguments to support the niche construction perspective, and to extend the variational approach to niche construction to current perspectives in various scientific fields. © 2018 The Authors.

Loss of quiescence and self-renewal capacity of hematopoietic stem cell in an in vitro leukemic niche.

Science.gov (United States)

Vanegas, Natalia-Del Pilar; Vernot, Jean-Paul

2017-01-01

Leukemic and mesenchymal stem cells interact in the leukemic microenvironment and affect each other differently. This interplay has also important implications for the hematopoietic stem cell (HSC) biology and function. This study evaluated human HSC self-renewal potential and quiescence in an in vitro leukemic niche without leukemic cells. A leukemic niche was established by co-culturing mesenchymal stem cells with a fresh conditioned medium obtained from a leukemic (REH) cell line. After 3 days, the REH-conditioned medium was removed and freshly isolated CD34+ at a density of up to 100,000 cells/ml were added to the leukemic niche. CD34+ cell evaluations (cell cycle, self-renewal gene expression and migration capacity) were performed after 3 further days of co-culture. Additionally, we preliminary investigated the soluble factors present in the leukemic niche and their effect on the mesenchymal stem cells. Statistical significance was assessed by Student's t test or the nonparametric test Kolmogorov-Smirnov. By co-culturing normal mesenchymal stem cells with the REH-conditioned medium we showed that hematopoietic stem cells, normally in a quiescent state, enter cell cycle and proliferate. This loss of quiescence was accompanied by an increased expression of Ki-67 and c-Myc, two well-known cell proliferation-associated markers. Two central regulators of quiescence GATA2 and p53 were also down regulated. Importantly, two genes involved in HSC self-renewal, Klf4 and the histone-lysine N -methyltransferase enzyme Ezh2, were severely affected. On the contrary, c-Kit expression, the stem cell factor receptor, was upregulated in hematopoietic stem cells when compared to the normal niche. Interestingly, mesenchymal stem cells incubated with the REH-conditioned medium stopped growing, showed a flattened morphology with the appearance of small vacuoles, and importantly, became positive for the senescence-associated beta-galactosidase activity. Evaluation of the leukemic

Strategic Niche Management and Transition Management: different but complementary approaches

NARCIS (Netherlands)

D.A. Loorbach (Derk); R. van Raak (Ronald)

2006-01-01

textabstractThis discussion paper sets out to compare two different, yet related, approaches to achieve sustainable development and (technological) innovation. Strategic Niche Management (SNM) (Kemp, Schot et al. 1998; Weber 1999) emerged as a novel concept by the end of the 1990’s and is presented

Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans

Directory of Open Access Journals (Sweden)

Assaf Gottlieb

2017-11-01

Full Text Available Abstract Background Genome-wide association studies are useful for discovering genotype–phenotype associations but are limited because they require large cohorts to identify a signal, which can be population-specific. Mapping genetic variation to genes improves power and allows the effects of both protein-coding variation as well as variation in expression to be combined into “gene level” effects. Methods Previous work has shown that warfarin dose can be predicted using information from genetic variation that affects protein-coding regions. Here, we introduce a method that improves dose prediction by integrating tissue-specific gene expression. In particular, we use drug pathways and expression quantitative trait loci knowledge to impute gene expression—on the assumption that differential expression of key pathway genes may impact dose requirement. We focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of warfarin within training and validation sets comprising both European and African-descent individuals. Results We build gene-tissue signatures associated with warfarin dose in a cohort-specific manner and identify a signature of 11 gene-tissue pairs that significantly augments the International Warfarin Pharmacogenetics Consortium dosage-prediction algorithm in both populations. Conclusions Our results demonstrate that imputed expression can improve dose prediction and bridge population-specific compositions. MATLAB code is available at https://github.com/assafgo/warfarin-cohort

Ecological niche partitioning between Anopheles gambiae molecular forms in Cameroon: the ecological side of speciation

Directory of Open Access Journals (Sweden)

Fotsing Jean-Marie

2009-05-01

Full Text Available Abstract Background Speciation among members of the Anopheles gambiae complex is thought to be promoted by disruptive selection and ecological divergence acting on sets of adaptation genes protected from recombination by polymorphic paracentric chromosomal inversions. However, shared chromosomal polymorphisms between the M and S molecular forms of An. gambiae and insufficient information about their relationship with ecological divergence challenge this view. We used Geographic Information Systems, Ecological Niche Factor Analysis, and Bayesian multilocus genetic clustering to explore the nature and extent of ecological and chromosomal differentiation of M and S across all the biogeographic domains of Cameroon in Central Africa, in order to understand the role of chromosomal arrangements in ecological specialisation within and among molecular forms. Results Species distribution modelling with presence-only data revealed differences in the ecological niche of both molecular forms and the sibling species, An. arabiensis. The fundamental environmental envelope of the two molecular forms, however, overlapped to a large extent in the rainforest, where they occurred in sympatry. The S form had the greatest niche breadth of all three taxa, whereas An. arabiensis and the M form had the smallest niche overlap. Correspondence analysis of M and S karyotypes confirmed that molecular forms shared similar combinations of chromosomal inversion arrangements in response to the eco-climatic gradient defining the main biogeographic domains occurring across Cameroon. Savanna karyotypes of M and S, however, segregated along the smaller-scale environmental gradient defined by the second ordination axis. Population structure analysis identified three chromosomal clusters, each containing a mixture of M and S specimens. In both M and S, alternative karyotypes were segregating in contrasted environments, in agreement with a strong ecological adaptive value of

Drosophila Glypicans Regulate Follicle Stem Cell Maintenance and Niche Competition.

Science.gov (United States)

Su, Tsu-Yi; Nakato, Eriko; Choi, Pui Yee; Nakato, Hiroshi

2018-04-09

Adult stem cells reside in specialized microenvironments, called niches, which provide signals for stem cells to maintain their undifferentiated and self-renewing state. To maintain stem cell quality, several types of stem cells are known to be regularly replaced by progenitor cells through niche competition. However, the cellular and molecular bases for stem cell competition for niche occupancy are largely unknown. Here, we show that two Drosophila members of the glypican family of heparan sulfate proteoglycans (HSPGs), Dally and Dally-like (Dlp), differentially regulate follicle stem cell (FSC) maintenance and FSC competitiveness for niche occupancy. Lineage analyses of glypican mutant FSC clones showed that dally is essential for normal FSC maintenance. In contrast, dlp is a hyper-competitive mutation: dlp mutant FSC progenitors often eventually occupy the entire epithelial sheet. RNAi knockdown experiments showed that Dally and Dlp play both partially redundant and distinct roles in regulating Jak/Stat, Wg and Hh signaling in FSCs. The Drosophila FSC system offers a powerful genetic model to study the mechanisms by which HSPGs exert specific functions in stem cell replacement and competition. Copyright © 2018, Genetics.

Integrative characterization of germ cell-specific genes from mouse spermatocyte UniGene library

Directory of Open Access Journals (Sweden)

Eddy Edward M

2007-07-01

Full Text Available Abstract Background The primary regulator of spermatogenesis, a highly ordered and tightly regulated developmental process, is an intrinsic genetic program involving male germ cell-specific genes. Results We analyzed the mouse spermatocyte UniGene library containing 2155 gene-oriented transcript clusters. We predict that 11% of these genes are testis-specific and systematically identified 24 authentic genes specifically and abundantly expressed in the testis via in silico and in vitro approaches. Northern blot analysis disclosed various transcript characteristics, such as expression level, size and the presence of isoform. Expression analysis revealed developmentally regulated and stage-specific expression patterns in all of the genes. We further analyzed the genes at the protein and cellular levels. Transfection assays performed using GC-2 cells provided information on the cellular characteristics of the gene products. In addition, antibodies were generated against proteins encoded by some of the genes to facilitate their identification and characterization in spermatogenic cells and sperm. Our data suggest that a number of the gene products are implicated in transcriptional regulation, nuclear integrity, sperm structure and motility, and fertilization. In particular, we found for the first time that Mm.333010, predicted to contain a trypsin-like serine protease domain, is a sperm acrosomal protein. Conclusion We identify 24 authentic genes with spermatogenic cell-specific expression, and provide comprehensive information about the genes. Our findings establish a new basis for future investigation into molecular mechanisms underlying male reproduction.

Stem Cell Plasticity and Niche Dynamics in Cancer Progression.

Science.gov (United States)

Picco, Noemi; Gatenby, Robert A; Anderson, Alexander R A

2017-03-01

Cancer stem cells (CSCs) have been hypothesized to initiate and drive tumor growth and recurrence due to their self-renewal ability. If correct, this hypothesis implies that successful therapy must focus primarily on eradication of this CSC fraction. However, recent evidence suggests stemness is niche dependent and may represent one of many phenotypic states that can be accessed by many cancer genotypes when presented with specific environmental cues. A better understanding of the relationship of stemness to niche-related phenotypic plasticity could lead to alternative treatment strategies. Here, we investigate the role of environmental context in the expression of stem-like cell properties through in-silico simulation of ductal carcinoma. We develop a two-dimensional hybrid discrete-continuum cellular automata model to describe the single-cell scale dynamics of multicellular tissue formation. Through a suite of simulations, we investigate interactions between a phenotypically heterogeneous cancer cell population and a dynamic environment. We generate homeostatic ductal structures that consist of a mixture of stem and differentiated cells governed by both intracellular and environmental dynamics. We demonstrate that a wide spectrum of tumor-like histologies can result from these structures by varying microenvironmental parameters. Niche driven phenotypic plasticity offers a simple first-principle explanation for the diverse ductal structures observed in histological sections from breast cancer. Conventional models of carcinogenesis largely focus on mutational events. We demonstrate that variations in the environmental niche can produce intraductal cancers independent of genetic changes in the resident cells. Therapies targeting the microenvironmental niche may offer an alternative cancer prevention strategy.

GSMA: Gene Set Matrix Analysis, An Automated Method for Rapid Hypothesis Testing of Gene Expression Data

Directory of Open Access Journals (Sweden)

Chris Cheadle

2007-01-01

Full Text Available Background: Microarray technology has become highly valuable for identifying complex global changes in gene expression patterns. The assignment of functional information to these complex patterns remains a challenging task in effectively interpreting data and correlating results from across experiments, projects and laboratories. Methods which allow the rapid and robust evaluation of multiple functional hypotheses increase the power of individual researchers to data mine gene expression data more efficiently.Results: We have developed (gene set matrix analysis GSMA as a useful method for the rapid testing of group-wise up- or downregulation of gene expression simultaneously for multiple lists of genes (gene sets against entire distributions of gene expression changes (datasets for single or multiple experiments. The utility of GSMA lies in its flexibility to rapidly poll gene sets related by known biological function or as designated solely by the end-user against large numbers of datasets simultaneously.Conclusions: GSMA provides a simple and straightforward method for hypothesis testing in which genes are tested by groups across multiple datasets for patterns of expression enrichment.

Intersexual Trophic Niche Partitioning in an Ant-Eating spider (Araneae: Zodariidae)

DEFF Research Database (Denmark)

Pekár, Stanislav; Martisová, Martina; Bilde, T.

2011-01-01

lead to higher energy demands in females driven by fecundity selection, while males invest in mate searching. We tested predictions of the two hypotheses underlying intersexual trophic niche partitioning in a natural population of spiders. Zodarion jozefienae spiders specialize on Messor barbarus ants...... that are polymorphic in body size and hence comprise potential trophic niches for the spider, making this system well-suited to study intersexual trophic niche partitioning. Methodology/Principal Findings Comparative analysis of trophic morphology (the chelicerae) and body size of males, females and juveniles...... demonstrated highly female biased SSD (Sexual Size Dimorphism) in body size, body weight, and in the size of chelicerae, the latter arising from sex-specific growth patterns in trophic morphology. In the field, female spiders actively selected ant sub-castes that were larger than the average prey size...

Annotating gene sets by mining large literature collections with protein networks.

Science.gov (United States)

Wang, Sheng; Ma, Jianzhu; Yu, Michael Ku; Zheng, Fan; Huang, Edward W; Han, Jiawei; Peng, Jian; Ideker, Trey

2018-01-01

Analysis of patient genomes and transcriptomes routinely recognizes new gene sets associated with human disease. Here we present an integrative natural language processing system which infers common functions for a gene set through automatic mining of the scientific literature with biological networks. This system links genes with associated literature phrases and combines these links with protein interactions in a single heterogeneous network. Multiscale functional annotations are inferred based on network distances between phrases and genes and then visualized as an ontology of biological concepts. To evaluate this system, we predict functions for gene sets representing known pathways and find that our approach achieves substantial improvement over the conventional text-mining baseline method. Moreover, our system discovers novel annotations for gene sets or pathways without previously known functions. Two case studies demonstrate how the system is used in discovery of new cancer-related pathways with ontological annotations.

Making Blood: The Haematopoietic Niche throughout Ontogeny

Directory of Open Access Journals (Sweden)

Mohammad A. Al-Drees

2015-01-01

Full Text Available Approximately one-quarter of all cells in the adult human body are blood cells. The haematopoietic system is therefore massive in scale and requires exquisite regulation to be maintained under homeostatic conditions. It must also be able to respond when needed, such as during infection or following blood loss, to produce more blood cells. Supporting cells serve to maintain haematopoietic stem and progenitor cells during homeostatic and pathological conditions. This coalition of supportive cell types, organised in specific tissues, is termed the haematopoietic niche. Haematopoietic stem and progenitor cells are generated in a number of distinct locations during mammalian embryogenesis. These stem and progenitor cells migrate to a variety of anatomical locations through the conceptus until finally homing to the bone marrow shortly before birth. Under stress, extramedullary haematopoiesis can take place in regions that are typically lacking in blood-producing activity. Our aim in this review is to examine blood production throughout the embryo and adult, under normal and pathological conditions, to identify commonalities and distinctions between each niche. A clearer understanding of the mechanism underlying each haematopoietic niche can be applied to improving ex vivo cultures of haematopoietic stem cells and potentially lead to new directions for transplantation medicine.

Development and molecular composition of the hepatic progenitor cell niche.

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Vestentoft, Peter Siig

2013-05-01

, we examined several genes upregulated in a global gene expression array conducted on one of these models, in which progenitor cells are activated. The protein expression patterns were evaluated in our collections of human embryonic and fetal livers, human liver diseases, and rodent hepatic injury models. When analyzing standard histological liver sections underlying connections and tissue architecture are not immediately evident. We therefore developed models for digitally reconstructing not only protein expression in serially cut tissue sections, but also vessels of the portal area. Article I constituted our earliest attempts to create 3D reconstructions of biological material. Human embryonic stem cell cultures were previously thought to consist of homogenously undifferentiated cells. The protocols for 3D reconstructions developed in this study demonstrated micro heterogeneity in expression of differentiation markers and provided the basis for later reconstructions of hepatic tissues. In article II we examined the expression patterns of chosen proteins seen upregulated in the gene array as well as classical hepatocytic and cholangiocytic markers in human liver disease and during prenatal development. Previous studies had indicated direct connections between activated progenitor cells apparently isolated in the parenchyma and the intrahepatic biliary tree. Our developed protocols for 3D reconstructions visually demonstrated direct connections between these entities. Analysis of protein expression in prenatal liver revealed the formation of the intrahepatic tree to occur through a special form of asymmetric tubulogenesis, only recently described in mice. In order to describe the composition of the hepatic progenitor cell niche and the localization of cell surface proteins in article III, the expression patterns of certain genes upregulated in the gene array analysis were analyzed in different models of rodent liver regeneration. We observed that the extracellular

Generation of a functional and durable vascular niche by the adenoviral E4ORF1 gene.

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Seandel, Marco; Butler, Jason M; Kobayashi, Hideki; Hooper, Andrea T; White, Ian A; Zhang, Fan; Vertes, Eva L; Kobayashi, Mariko; Zhang, Yan; Shmelkov, Sergey V; Hackett, Neil R; Rabbany, Sina; Boyer, Julie L; Rafii, Shahin

2008-12-09

Vascular cells contribute to organogenesis and tumorigenesis by producing unknown factors. Primary endothelial cells (PECs) provide an instructive platform for identifying factors that support stem cell and tumor homeostasis. However, long-term maintenance of PECs requires stimulation with cytokines and serum, resulting in loss of their angiogenic properties. To circumvent this hurdle, we have discovered that the adenoviral E4ORF1 gene product maintains long-term survival and facilitates organ-specific purification of PECs, while preserving their vascular repertoire for months, in serum/cytokine-free cultures. Lentiviral introduction of E4ORF1 into human PECs (E4ORF1(+) ECs) increased the long-term survival of these cells in serum/cytokine-free conditions, while preserving their in vivo angiogenic potential for tubulogenesis and sprouting. Although E4ORF1, in the absence of mitogenic signals, does not induce proliferation of ECs, stimulation with VEGF-A and/or FGF-2 induced expansion of E4ORF1(+) ECs in a contact-inhibited manner. Indeed, VEGF-A-induced phospho MAPK activation of E4ORF1(+) ECs is comparable with that of naive PECs, suggesting that the VEGF receptors remain functional upon E4ORF1 introduction. E4ORF1(+) ECs inoculated in implanted Matrigel plugs formed functional, patent, humanized microvessels that connected to the murine circulation. E4ORF1(+) ECs also incorporated into neo-vessels of human tumor xenotransplants and supported serum/cytokine-free expansion of leukemic and embryonal carcinoma cells. E4ORF1 augments survival of PECs in part by maintaining FGF-2/FGF-R1 signaling and through tonic Ser-473 phosphorylation of Akt, thereby activating the mTOR and NF-kappaB pathways. Therefore, E4ORF1(+) ECs establish an Akt-dependent durable vascular niche not only for expanding stem and tumor cells but also for interrogating the roles of vascular cells in regulating organ-specific vascularization and tumor neo-angiogenesis.

Generation of a functional and durable vascular niche by the adenoviral E4ORF1 gene

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Seandel, Marco; Butler, Jason M.; Kobayashi, Hideki; Hooper, Andrea T.; White, Ian A.; Zhang, Fan; Vertes, Eva L.; Kobayashi, Mariko; Zhang, Yan; Shmelkov, Sergey V.; Hackett, Neil R.; Rabbany, Sina; Boyer, Julie L.; Rafii, Shahin

2008-01-01

Vascular cells contribute to organogenesis and tumorigenesis by producing unknown factors. Primary endothelial cells (PECs) provide an instructive platform for identifying factors that support stem cell and tumor homeostasis. However, long-term maintenance of PECs requires stimulation with cytokines and serum, resulting in loss of their angiogenic properties. To circumvent this hurdle, we have discovered that the adenoviral E4ORF1 gene product maintains long-term survival and facilitates organ-specific purification of PECs, while preserving their vascular repertoire for months, in serum/cytokine-free cultures. Lentiviral introduction of E4ORF1 into human PECs (E4ORF1+ ECs) increased the long-term survival of these cells in serum/cytokine-free conditions, while preserving their in vivo angiogenic potential for tubulogenesis and sprouting. Although E4ORF1, in the absence of mitogenic signals, does not induce proliferation of ECs, stimulation with VEGF-A and/or FGF-2 induced expansion of E4ORF1+ ECs in a contact-inhibited manner. Indeed, VEGF-A-induced phospho MAPK activation of E4ORF1+ ECs is comparable with that of naive PECs, suggesting that the VEGF receptors remain functional upon E4ORF1 introduction. E4ORF1+ ECs inoculated in implanted Matrigel plugs formed functional, patent, humanized microvessels that connected to the murine circulation. E4ORF1+ ECs also incorporated into neo-vessels of human tumor xenotransplants and supported serum/cytokine-free expansion of leukemic and embryonal carcinoma cells. E4ORF1 augments survival of PECs in part by maintaining FGF-2/FGF-R1 signaling and through tonic Ser-473 phosphorylation of Akt, thereby activating the mTOR and NF-κB pathways. Therefore, E4ORF1+ ECs establish an Akt-dependent durable vascular niche not only for expanding stem and tumor cells but also for interrogating the roles of vascular cells in regulating organ-specific vascularization and tumor neo-angiogenesis. PMID:19036927

Stem Cell Spheroids and Ex Vivo Niche Modeling: Rationalization and Scaling-Up.

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Chimenti, Isotta; Massai, Diana; Morbiducci, Umberto; Beltrami, Antonio Paolo; Pesce, Maurizio; Messina, Elisa

2017-04-01

Improved protocols/devices for in vitro culture of 3D cell spheroids may provide essential cues for proper growth and differentiation of stem/progenitor cells (S/PCs) in their niche, allowing preservation of specific features, such as multi-lineage potential and paracrine activity. Several platforms have been employed to replicate these conditions and to generate S/PC spheroids for therapeutic applications. However, they incompletely reproduce the niche environment, with partial loss of its highly regulated network, with additional hurdles in the field of cardiac biology, due to debated resident S/PCs therapeutic potential and clinical translation. In this contribution, the essential niche conditions (metabolic, geometric, mechanical) that allow S/PCs maintenance/commitment will be discussed. In particular, we will focus on both existing bioreactor-based platforms for the culture of S/PC as spheroids, and on possible criteria for the scaling-up of niche-like spheroids, which could be envisaged as promising tools for personalized cardiac regenerative medicine, as well as for high-throughput drug screening.

Phylogenetics and evolution of Trx SET genes in fully sequenced land plants.

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Zhu, Xinyu; Chen, Caoyi; Wang, Baohua

2012-04-01

Plant Trx SET proteins are involved in H3K4 methylation and play a key role in plant floral development. Genes encoding Trx SET proteins constitute a multigene family in which the copy number varies among plant species and functional divergence appears to have occurred repeatedly. To investigate the evolutionary history of the Trx SET gene family, we made a comprehensive evolutionary analysis on this gene family from 13 major representatives of green plants. A novel clustering (here named as cpTrx clade), which included the III-1, III-2, and III-4 orthologous groups, previously resolved was identified. Our analysis showed that plant Trx proteins possessed a variety of domain organizations and gene structures among paralogs. Additional domains such as PHD, PWWP, and FYR were early integrated into primordial SET-PostSET domain organization of cpTrx clade. We suggested that the PostSET domain was lost in some members of III-4 orthologous group during the evolution of land plants. At least four classes of gene structures had been formed at the early evolutionary stage of land plants. Three intronless orphan Trx SET genes from the Physcomitrella patens (moss) were identified, and supposedly, their parental genes have been eliminated from the genome. The structural differences among evolutionary groups of plant Trx SET genes with different functions were described, contributing to the design of further experimental studies.

Selecting Question-Specific Genes to Reduce Incongruence in Phylogenomics: A Case Study of Jawed Vertebrate Backbone Phylogeny.

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Chen, Meng-Yun; Liang, Dan; Zhang, Peng

2015-11-01

Incongruence between different phylogenomic analyses is the main challenge faced by phylogeneticists in the genomic era. To reduce incongruence, phylogenomic studies normally adopt some data filtering approaches, such as reducing missing data or using slowly evolving genes, to improve the signal quality of data. Here, we assembled a phylogenomic data set of 58 jawed vertebrate taxa and 4682 genes to investigate the backbone phylogeny of jawed vertebrates under both concatenation and coalescent-based frameworks. To evaluate the efficiency of extracting phylogenetic signals among different data filtering methods, we chose six highly intractable internodes within the backbone phylogeny of jawed vertebrates as our test questions. We found that our phylogenomic data set exhibits substantial conflicting signal among genes for these questions. Our analyses showed that non-specific data sets that are generated without bias toward specific questions are not sufficient to produce consistent results when there are several difficult nodes within a phylogeny. Moreover, phylogenetic accuracy based on non-specific data is considerably influenced by the size of data and the choice of tree inference methods. To address such incongruences, we selected genes that resolve a given internode but not the entire phylogeny. Notably, not only can this strategy yield correct relationships for the question, but it also reduces inconsistency associated with data sizes and inference methods. Our study highlights the importance of gene selection in phylogenomic analyses, suggesting that simply using a large amount of data cannot guarantee correct results. Constructing question-specific data sets may be more powerful for resolving problematic nodes. © The Author(s) 2015. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The United States pork niche market phenomenon.

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Honeyman, M S; Pirog, R S; Huber, G H; Lammers, P J; Hermann, J R

2006-08-01

After the broad industrialization of the US pork industry, there has been a development of niche markets for export and domestic pork; that is, there is a pork niche market phenomenon. The US pork niche market phenomenon is characterized, and 2 of the major markets are explained in detail. With the Midwest's tradition of a diversified family-based agriculture and record low hog prices of the late 1990s, the conditions were conducive for this phenomenon to develop. Pork niche markets utilize various sales methods including Internet sales, local abattoir sales, direct marketing, farmer networks, and targeting to organized groups. In 2003, there were approximately 35 to 40 active pork niche marketing efforts in Iowa. The Berkshire breed is an example of a swine breed that has had a recent resurgence because of niche markets. Berkshire pork is known for tenderness and excellent quality. Berkshire registrations have increased 4-fold in the last 10 yr. One of the larger niche marketers of "natural pork" is Niman Ranch Pork, which has more than 400 farmer-producers and processes about 2,500 pigs weekly. Many US consumers of pork are interested in issues concerning the environment, food safety, pig welfare, and pig farm ownership and structure. These consumers may be willing to pay more for pork from farmers who are also concerned about these issues. Small- and medium-sized swine farmers are active in pork niche markets. Niche markets claim product differentiation by superior or unique product quality and social attributes. Quality attributes include certain swine breeds, and meat quality, freshness, taste or flavor, and tenderness. Social or credence attributes often are claimed and include freedom from antibiotics and growth promotants; local family farm production; natural, organic, outdoor, or bedded rearing; humane rearing; known origin; environmentally friendly production; and the absence of animal by-products in the feed. Niche pork markets and alternative swine

A bottleneck model of set-specific capture.

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Katherine Sledge Moore

Full Text Available Set-specific contingent attentional capture is a particularly strong form of capture that occurs when multiple attentional sets guide visual search (e.g., "search for green letters" and "search for orange letters". In this type of capture, a potential target that matches one attentional set (e.g. a green stimulus impairs the ability to identify a temporally proximal target that matches another attentional set (e.g. an orange stimulus. In the present study, we investigated whether set-specific capture stems from a bottleneck in working memory or from a depletion of limited resources that are distributed across multiple attentional sets. In each trial, participants searched a rapid serial visual presentation (RSVP stream for up to three target letters (T1-T3 that could appear in any of three target colors (orange, green, or lavender. The most revealing findings came from trials in which T1 and T2 matched different attentional sets and were both identified. In these trials, T3 accuracy was lower when it did not match T1's set than when it did match, but only when participants failed to identify T2. These findings support a bottleneck model of set-specific capture in which a limited-capacity mechanism in working memory enhances only one attentional set at a time, rather than a resource model in which processing capacity is simultaneously distributed across multiple attentional sets.

Large-scale modeling of condition-specific gene regulatory networks by information integration and inference.

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Ellwanger, Daniel Christian; Leonhardt, Jörn Florian; Mewes, Hans-Werner

2014-12-01

Understanding how regulatory networks globally coordinate the response of a cell to changing conditions, such as perturbations by shifting environments, is an elementary challenge in systems biology which has yet to be met. Genome-wide gene expression measurements are high dimensional as these are reflecting the condition-specific interplay of thousands of cellular components. The integration of prior biological knowledge into the modeling process of systems-wide gene regulation enables the large-scale interpretation of gene expression signals in the context of known regulatory relations. We developed COGERE (http://mips.helmholtz-muenchen.de/cogere), a method for the inference of condition-specific gene regulatory networks in human and mouse. We integrated existing knowledge of regulatory interactions from multiple sources to a comprehensive model of prior information. COGERE infers condition-specific regulation by evaluating the mutual dependency between regulator (transcription factor or miRNA) and target gene expression using prior information. This dependency is scored by the non-parametric, nonlinear correlation coefficient η(2) (eta squared) that is derived by a two-way analysis of variance. We show that COGERE significantly outperforms alternative methods in predicting condition-specific gene regulatory networks on simulated data sets. Furthermore, by inferring the cancer-specific gene regulatory network from the NCI-60 expression study, we demonstrate the utility of COGERE to promote hypothesis-driven clinical research. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Ecological Niche Modelling of Bank Voles in Western Europe

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Sara Amirpour Haredasht

2013-01-01

Full Text Available The bank vole (Myodes glareolus is the natural host of Puumala virus (PUUV in vast areas of Europe. PUUV is one of the hantaviruses which are transmitted to humans by infected rodents. PUUV causes a general mild form of hemorrhagic fever with renal syndrome (HFRS called nephropathia epidemica (NE. Vector-borne and zoonotic diseases generally display clear spatial patterns due to different space-dependent factors. Land cover influences disease transmission by controlling both the spatial distribution of vectors or hosts, as well as by facilitating the human contact with them. In this study the use of ecological niche modelling (ENM for predicting the geographical distribution of bank vole population on the basis of spatial climate information is tested. The Genetic Algorithm for Rule-set Prediction (GARP is used to model the ecological niche of bank voles in Western Europe. The meteorological data, land cover types and geo-referenced points representing the locations of the bank voles (latitude/longitude in the study area are used as the primary model input value. The predictive accuracy of the bank vole ecologic niche model was significant (training accuracy of 86%. The output of the GARP models based on the 50% subsets of points used for testing the model showed an accuracy of 75%. Compared with random models, the probability of such high predictivity was low (χ2 tests, p < 10−6. As such, the GARP models were predictive and the used ecologic niche model indeed indicates the ecologic requirements of bank voles. This approach successfully identified the areas of infection risk across the study area. The result suggests that the niche modelling approach can be implemented in a next step towards the development of new tools for monitoring the bank vole’s population.

Ecological niche modelling of bank voles in Western Europe.

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Amirpour Haredasht, Sara; Barrios, Miguel; Farifteh, Jamshid; Maes, Piet; Clement, Jan; Verstraeten, Willem W; Tersago, Katrien; Van Ranst, Marc; Coppin, Pol; Berckmans, Daniel; Aerts, Jean-Marie

2013-01-28

The bank vole (Myodes glareolus) is the natural host of Puumala virus (PUUV) in vast areas of Europe. PUUV is one of the hantaviruses which are transmitted to humans by infected rodents. PUUV causes a general mild form of hemorrhagic fever with renal syndrome (HFRS) called nephropathia epidemica (NE). Vector-borne and zoonotic diseases generally display clear spatial patterns due to different space-dependent factors. Land cover influences disease transmission by controlling both the spatial distribution of vectors or hosts, as well as by facilitating the human contact with them. In this study the use of ecological niche modelling (ENM) for predicting the geographical distribution of bank vole population on the basis of spatial climate information is tested. The Genetic Algorithm for Rule-set Prediction (GARP) is used to model the ecological niche of bank voles in Western Europe. The meteorological data, land cover types and geo-referenced points representing the locations of the bank voles (latitude/longitude) in the study area are used as the primary model input value. The predictive accuracy of the bank vole ecologic niche model was significant (training accuracy of 86%). The output of the GARP models based on the 50% subsets of points used for testing the model showed an accuracy of 75%. Compared with random models, the probability of such high predictivity was low (χ(2) tests, p < 10(-6)). As such, the GARP models were predictive and the used ecologic niche model indeed indicates the ecologic requirements of bank voles. This approach successfully identified the areas of infection risk across the study area. The result suggests that the niche modelling approach can be implemented in a next step towards the development of new tools for monitoring the bank vole's population.

Classification of Non-Small Cell Lung Cancer Using Significance Analysis of Microarray-Gene Set Reduction Algorithm

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Lei Zhang

2016-01-01

Full Text Available Among non-small cell lung cancer (NSCLC, adenocarcinoma (AC, and squamous cell carcinoma (SCC are two major histology subtypes, accounting for roughly 40% and 30% of all lung cancer cases, respectively. Since AC and SCC differ in their cell of origin, location within the lung, and growth pattern, they are considered as distinct diseases. Gene expression signatures have been demonstrated to be an effective tool for distinguishing AC and SCC. Gene set analysis is regarded as irrelevant to the identification of gene expression signatures. Nevertheless, we found that one specific gene set analysis method, significance analysis of microarray-gene set reduction (SAMGSR, can be adopted directly to select relevant features and to construct gene expression signatures. In this study, we applied SAMGSR to a NSCLC gene expression dataset. When compared with several novel feature selection algorithms, for example, LASSO, SAMGSR has equivalent or better performance in terms of predictive ability and model parsimony. Therefore, SAMGSR is a feature selection algorithm, indeed. Additionally, we applied SAMGSR to AC and SCC subtypes separately to discriminate their respective stages, that is, stage II versus stage I. Few overlaps between these two resulting gene signatures illustrate that AC and SCC are technically distinct diseases. Therefore, stratified analyses on subtypes are recommended when diagnostic or prognostic signatures of these two NSCLC subtypes are constructed.

Investigating the effect of paralogs on microarray gene-set analysis

LENUS (Irish Health Repository)

Faure, Andre J

2011-01-24

Abstract Background In order to interpret the results obtained from a microarray experiment, researchers often shift focus from analysis of individual differentially expressed genes to analyses of sets of genes. These gene-set analysis (GSA) methods use previously accumulated biological knowledge to group genes into sets and then aim to rank these gene sets in a way that reflects their relative importance in the experimental situation in question. We suspect that the presence of paralogs affects the ability of GSA methods to accurately identify the most important sets of genes for subsequent research. Results We show that paralogs, which typically have high sequence identity and similar molecular functions, also exhibit high correlation in their expression patterns. We investigate this correlation as a potential confounding factor common to current GSA methods using Indygene http:\\/\\/www.cbio.uct.ac.za\\/indygene, a web tool that reduces a supplied list of genes so that it includes no pairwise paralogy relationships above a specified sequence similarity threshold. We use the tool to reanalyse previously published microarray datasets and determine the potential utility of accounting for the presence of paralogs. Conclusions The Indygene tool efficiently removes paralogy relationships from a given dataset and we found that such a reduction, performed prior to GSA, has the ability to generate significantly different results that often represent novel and plausible biological hypotheses. This was demonstrated for three different GSA approaches when applied to the reanalysis of previously published microarray datasets and suggests that the redundancy and non-independence of paralogs is an important consideration when dealing with GSA methodologies.

THE NICHE CONSTRUCTION PERSPECTIVE: A CRITICAL APPRAISAL*

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Scott-Phillips, Thomas C; Laland, Kevin N; Shuker, David M; Dickins, Thomas E; West, Stuart A

2014-01-01

Niche construction refers to the activities of organisms that bring about changes in their environments, many of which are evolutionarily and ecologically consequential. Advocates of niche construction theory (NCT) believe that standard evolutionary theory fails to recognize the full importance of niche construction, and consequently propose a novel view of evolution, in which niche construction and its legacy over time (ecological inheritance) are described as evolutionary processes, equivalent in importance to natural selection. Here, we subject NCT to critical evaluation, in the form of a collaboration between one prominent advocate of NCT, and a team of skeptics. We discuss whether niche construction is an evolutionary process, whether NCT obscures or clarifies how natural selection leads to organismal adaptation, and whether niche construction and natural selection are of equivalent explanatory importance. We also consider whether the literature that promotes NCT overstates the significance of niche construction, whether it is internally coherent, and whether it accurately portrays standard evolutionary theory. Our disagreements reflect a wider dispute within evolutionary theory over whether the neo-Darwinian synthesis is in need of reformulation, as well as different usages of some key terms (e.g., evolutionary process). PMID:24325256

The niche party concept and its measurement

OpenAIRE

Meyer, Thomas M; Miller, Bernhard

2015-01-01

The concept of the niche party has become increasingly popular in analyses of party competition. Yet, existing approaches vary in their definitions and their measurement approaches. We propose using a minimal definition that allows us to compare political parties in terms of their ?nicheness?. We argue that the conceptual core of the niche party concept is based on issue emphasis and that a niche party emphasizes policy areas neglected by its rivals. Based on this definition, we propose a con...

Does niche divergence accompany allopatric divergence in Aphelocoma jays as predicted under ecological speciation? Insights from tests with niche models.

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McCormack, John E; Zellmer, Amanda J; Knowles, L Lacey

2010-05-01

The role of ecology in the origin of species has been the subject of long-standing interest to evolutionary biologists. New sources of spatially explicit ecological data allow for large-scale tests of whether speciation is associated with niche divergence or whether closely related species tend to be similar ecologically (niche conservatism). Because of the confounding effects of spatial autocorrelation of environmental variables, we generate null expectations for niche divergence for both an ecological-niche modeling and a multivariate approach to address the question: do allopatrically distributed taxa occupy similar niches? In a classic system for the study of niche evolution--the Aphelocoma jays--we show that there is little evidence for niche divergence among Mexican Jay (A. ultramarina) lineages in the process of speciation, contrary to previous results. In contrast, Aphelocoma species that exist in partial sympatry in some regions show evidence for niche divergence. Our approach is widely applicable to the many cases of allopatric lineages in the beginning stages of speciation. These results do not support an ecological speciation model for Mexican Jay lineages because, in most cases, the allopatric environments they occupy are not significantly more divergent than expected under a null model.

Plant stem cell niches.

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Stahl, Yvonne; Simon, Rüdiger

2005-01-01

Stem cells are required to support the indeterminate growth style of plants. Meristems are a plants stem cell niches that foster stem cell survival and the production of descendants destined for differentiation. In shoot meristems, stem cell fate is decided at the populational level. The size of the stem cell domain at the meristem tip depends on signals that are exchanged with cells of the organizing centre underneath. In root meristems, individual stem cells are controlled by direct interaction with cells of the quiescent centre that lie in the immediate neighbourhood. Analysis of the interactions and signaling processes in the stem cell niches has delivered some insights into the molecules that are involved and revealed that the two major niches for plant stem cells are more similar than anticipated.

Bone Marrow Vascular Niche: Home for Hematopoietic Stem Cells

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Ningning He

2014-01-01

Full Text Available Though discovered later than osteoblastic niche, vascular niche has been regarded as an alternative indispensable niche operating regulation on hematopoietic stem cells (HSCs. As significant progresses gained on this type niche, it is gradually clear that the main work of vascular niche is undertaking to support hematopoiesis. However, compared to what have been defined in the mechanisms through which the osteoblastic niche regulates hematopoiesis, we know less in vascular niche. In this review, based on research data hitherto we will focus on component foundation and various functions of vascular niche that guarantee the normal hematopoiesis process within bone marrow microenvironments. And the possible pathways raised by various research results through which this environment undergoes its function will be discussed as well.

HU participates in expression of a specific set of genes required for growth and survival at acidic pH in Escherichia coli.

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Bi, Hongkai; Sun, Lianle; Fukamachi, Toshihiko; Saito, Hiromi; Kobayashi, Hiroshi

2009-05-01

The major histone-like Escherichia coli protein, HU, is composed of alpha and beta subunits respectively encoded by hupA and hupB in Escherichia coli. A mutant deficient in both hupA and hupB grew at a slightly slower rate than the wild type at pH 7.5. Growth of the mutant diminished with a decrease in pH, and no growth was observed at pH 4.6. Mutants of either hupA or hupB grew at all pH levels tested. The arginine-dependent survival at pH 2.5 was diminished approximately 60-fold by the deletion of both hupA and hupB, whereas the survival was slightly affected by the deletion of either hupA or hupB. The mRNA levels of adiA and adiC, which respectively encode arginine decarboxylase and arginine/agmatine antiporter, were low in the mutant deficient in both hupA and hupB. The deletion of both hupA and hupB had little effect on survival at pH 2.5 in the presence of glutamate or lysine, and expression of the genes for glutamate and lysine decarboxylases was not impaired by the deletion of the HU genes. These results suggest that HU regulates expression of the specific set of genes required for growth and survival in acidic environments.

Genome-Wide Temporal Expression Profiling in Caenorhabditis elegans Identifies a Core Gene Set Related to Long-Term Memory.

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Freytag, Virginie; Probst, Sabine; Hadziselimovic, Nils; Boglari, Csaba; Hauser, Yannick; Peter, Fabian; Gabor Fenyves, Bank; Milnik, Annette; Demougin, Philippe; Vukojevic, Vanja; de Quervain, Dominique J-F; Papassotiropoulos, Andreas; Stetak, Attila

2017-07-12

The identification of genes related to encoding, storage, and retrieval of memories is a major interest in neuroscience. In the current study, we analyzed the temporal gene expression changes in a neuronal mRNA pool during an olfactory long-term associative memory (LTAM) in Caenorhabditis elegans hermaphrodites. Here, we identified a core set of 712 (538 upregulated and 174 downregulated) genes that follows three distinct temporal peaks demonstrating multiple gene regulation waves in LTAM. Compared with the previously published positive LTAM gene set (Lakhina et al., 2015), 50% of the identified upregulated genes here overlap with the previous dataset, possibly representing stimulus-independent memory-related genes. On the other hand, the remaining genes were not previously identified in positive associative memory and may specifically regulate aversive LTAM. Our results suggest a multistep gene activation process during the formation and retrieval of long-term memory and define general memory-implicated genes as well as conditioning-type-dependent gene sets. SIGNIFICANCE STATEMENT The identification of genes regulating different steps of memory is of major interest in neuroscience. Identification of common memory genes across different learning paradigms and the temporal activation of the genes are poorly studied. Here, we investigated the temporal aspects of Caenorhabditis elegans gene expression changes using aversive olfactory associative long-term memory (LTAM) and identified three major gene activation waves. Like in previous studies, aversive LTAM is also CREB dependent, and CREB activity is necessary immediately after training. Finally, we define a list of memory paradigm-independent core gene sets as well as conditioning-dependent genes. Copyright © 2017 the authors 0270-6474/17/376661-12$15.00/0.

Principal Angle Enrichment Analysis (PAEA): Dimensionally Reduced Multivariate Gene Set Enrichment Analysis Tool.

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Clark, Neil R; Szymkiewicz, Maciej; Wang, Zichen; Monteiro, Caroline D; Jones, Matthew R; Ma'ayan, Avi

2015-11-01

Gene set analysis of differential expression, which identifies collectively differentially expressed gene sets, has become an important tool for biology. The power of this approach lies in its reduction of the dimensionality of the statistical problem and its incorporation of biological interpretation by construction. Many approaches to gene set analysis have been proposed, but benchmarking their performance in the setting of real biological data is difficult due to the lack of a gold standard. In a previously published work we proposed a geometrical approach to differential expression which performed highly in benchmarking tests and compared well to the most popular methods of differential gene expression. As reported, this approach has a natural extension to gene set analysis which we call Principal Angle Enrichment Analysis (PAEA). PAEA employs dimensionality reduction and a multivariate approach for gene set enrichment analysis. However, the performance of this method has not been assessed nor its implementation as a web-based tool. Here we describe new benchmarking protocols for gene set analysis methods and find that PAEA performs highly. The PAEA method is implemented as a user-friendly web-based tool, which contains 70 gene set libraries and is freely available to the community.

A minimal set of tissue-specific hypomethylated CpGs constitute epigenetic signatures of developmental programming.

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Alejandro Colaneri

Full Text Available Cell specific states of the chromatin are programmed during mammalian development. Dynamic DNA methylation across the developing embryo guides a program of repression, switching off genes in most cell types. Thus, the majority of the tissue specific differentially methylated sites (TS-DMS must be un-methylated CpGs.Comparison of expanded Methyl Sensitive Cut Counting data (eMSCC among four tissues (liver, testes, brain and kidney from three C57BL/6J mice, identified 138,052 differentially methylated sites of which 23,270 contain CpGs un-methylated in only one tissue (TS-DMS. Most of these CpGs were located in intergenic regions, outside of promoters, CpG islands or their shores, and up to 20% of them overlapped reported active enhancers. Indeed, tissue-specific enhancers were up to 30 fold enriched in TS-DMS. Testis showed the highest number of TS-DMS, but paradoxically their associated genes do not appear to be specific to the germ cell functions, but rather are involved in organism development. In the other tissues the differentially methylated genes are associated with tissue-specific physiological or anatomical functions. The identified sets of TS-DMS quantify epigenetic distances between tissues, generated during development. We applied this concept to measure the extent of reprogramming in the liver of mice exposed to in utero or early postnatal nutritional stress. Different protocols of food restriction reprogrammed the liver methylome in different but reproducible ways.Thus, each identified set of differentially methylated sites constituted an epigenetic signature that traced the developmental programing or the early nutritional reprogramming of each exposed mouse. We propose that our approach has the potential to outline a number of disease-associated epigenetic states. The composition of differentially methylated CpGs may vary with each situation, behaving as a composite variable, which can be used as a pre-symptomatic marker for

Macrophages Contribute to the Spermatogonial Niche in the Adult Testis

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Tony DeFalco

2015-08-01

Full Text Available The testis produces sperm throughout the male reproductive lifespan by balancing self-renewal and differentiation of spermatogonial stem cells (SSCs. Part of the SSC niche is thought to lie outside the seminiferous tubules of the testis; however, specific interstitial components of the niche that regulate spermatogonial divisions and differentiation remain undefined. We identified distinct populations of testicular macrophages, one of which lies on the surface of seminiferous tubules, in close apposition to areas of tubules enriched for undifferentiated spermatogonia. These macrophages express spermatogonial proliferation- and differentiation-inducing factors, such as colony-stimulating factor 1 (CSF1 and enzymes involved in retinoic acid (RA biosynthesis. We show that transient depletion of macrophages leads to a disruption in spermatogonial differentiation. These findings reveal an unexpected role for macrophages in the spermatogonial niche in the testis and raise the possibility that macrophages play previously unappreciated roles in stem/progenitor cell regulation in other tissues.

Variations in CCL3L gene cluster sequence and non-specific gene copy numbers

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Edberg Jeffrey C

2010-03-01

Full Text Available Abstract Background Copy number variations (CNVs of the gene CC chemokine ligand 3-like1 (CCL3L1 have been implicated in HIV-1 susceptibility, but the association has been inconsistent. CCL3L1 shares homology with a cluster of genes localized to chromosome 17q12, namely CCL3, CCL3L2, and, CCL3L3. These genes are involved in host defense and inflammatory processes. Several CNV assays have been developed for the CCL3L1 gene. Findings Through pairwise and multiple alignments of these genes, we have shown that the homology between these genes ranges from 50% to 99% in complete gene sequences and from 70-100% in the exonic regions, with CCL3L1 and CCL3L3 being identical. By use of MEGA 4 and BioEdit, we aligned sense primers, anti-sense primers, and probes used in several previously described assays against pre-multiple alignments of all four chemokine genes. Each set of probes and primers aligned and matched with overlapping sequences in at least two of the four genes, indicating that previously utilized RT-PCR based CNV assays are not specific for only CCL3L1. The four available assays measured median copies of 2 and 3-4 in European and African American, respectively. The concordance between the assays ranged from 0.44-0.83 suggesting individual discordant calls and inconsistencies with the assays from the expected gene coverage from the known sequence. Conclusions This indicates that some of the inconsistencies in the association studies could be due to assays that provide heterogenous results. Sequence information to determine CNV of the three genes separately would allow to test whether their association with the pathogenesis of a human disease or phenotype is affected by an individual gene or by a combination of these genes.

The niche construction perspective: a critical appraisal.

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Scott-Phillips, Thomas C; Laland, Kevin N; Shuker, David M; Dickins, Thomas E; West, Stuart A

2014-05-01

Niche construction refers to the activities of organisms that bring about changes in their environments, many of which are evolutionarily and ecologically consequential. Advocates of niche construction theory (NCT) believe that standard evolutionary theory fails to recognize the full importance of niche construction, and consequently propose a novel view of evolution, in which niche construction and its legacy over time (ecological inheritance) are described as evolutionary processes, equivalent in importance to natural selection. Here, we subject NCT to critical evaluation, in the form of a collaboration between one prominent advocate of NCT, and a team of skeptics. We discuss whether niche construction is an evolutionary process, whether NCT obscures or clarifies how natural selection leads to organismal adaptation, and whether niche construction and natural selection are of equivalent explanatory importance. We also consider whether the literature that promotes NCT overstates the significance of niche construction, whether it is internally coherent, and whether it accurately portrays standard evolutionary theory. Our disagreements reflect a wider dispute within evolutionary theory over whether the neo-Darwinian synthesis is in need of reformulation, as well as different usages of some key terms (e.g., evolutionary process). © 2013 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

Environmental filtering drives the shape and breadth of the seed germination niche in coastal plant communities.

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Fernández-Pascual, Eduardo; Pérez-Arcoiza, Adrián; Prieto, José Alberto; Díaz, Tomás E

2017-05-01

A phylogenetic comparative analysis of the seed germination niche was conducted in coastal plant communities of western Europe. Two hypotheses were tested, that (1) the germination niche shape (i.e. the preference for a set of germination cues as opposed to another) would differ between beaches and cliffs to prevent seedling emergence in the less favourable season (winter and summer, respectively); and (2) the germination niche breadth (i.e. the amplitude of germination cues) would be narrower in the seawards communities, where environmental filtering is stronger. Seeds of 30 specialist species of coastal plant communities were collected in natural populations of northern Spain. Their germination was measured in six laboratory treatments based on field temperatures. Germination niche shape was estimated as the best germination temperature. Germination niche breadth was calculated using Pielou's evenness index. Differences between plant communities in their germination niche shape and breadth were tested using phylogenetic generalized least squares regression (PGLS). Germination niche shape differed between communities, being warm-cued in beaches (best germination temperature = 20 °C) and cold-cued in cliffs (14 °C). Germination niche was narrowest in seawards beaches (Pielou's index = 0·89) and broadest in landwards beaches (0·99). Cliffs had an intermediate germination niche breadth (0·95). The relationship between niche and plant community had a positive phylogenetic signal for shape (Pagel's λ = 0·64) and a negative one for breadth (Pagel's λ = -1·71). Environmental filters shape the germination niche to prevent emergence in the season of highest threat for seedling establishment. The germination niche breadth is narrower in the communities with stronger environmental filters, but only in beaches. This study provides empirical support to a community-level generalization of the hypotheses about the environmental drivers of the germination

Host iron binding proteins acting as niche indicators for Neisseria meningitidis.

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Philip W Jordan

Full Text Available Neisseria meningitidis requires iron, and in the absence of iron alters its gene expression to increase iron acquisition and to make the best use of the iron it has. During different stages of colonization and infection available iron sources differ, particularly the host iron-binding proteins haemoglobin, transferrin, and lactoferrin. This study compared the transcriptional responses of N. meningitidis, when grown in the presence of these iron donors and ferric iron, using microarrays.Specific transcriptional responses to the different iron sources were observed, including genes that are not part of the response to iron restriction. Comparisons between growth on haemoglobin and either transferrin or lactoferrin identified changes in 124 and 114 genes, respectively, and 33 genes differed between growth on transferrin or lactoferrin. Comparison of gene expression from growth on haemoglobin or ferric iron showed that transcription is also affected by the entry of either haem or ferric iron into the cytoplasm. This is consistent with a model in which N. meningitidis uses the relative availability of host iron donor proteins as niche indicators.Growth in the presence of haemoglobin is associated with a response likely to be adaptive to survival within the bloodstream, which is supported by serum killing assays that indicate growth on haemoglobin significantly increases survival, and the response to lactoferrin is associated with increased expression of epithelial cell adhesins and oxidative stress response molecules. The transferrin receptor is the most highly transcribed receptor and has the fewest genes specifically induced in its presence, suggesting this is the favoured iron source for the bacterium. Most strikingly, the responses to haemoglobin, which is associated with unrestricted growth, indicates a low iron transcriptional profile, associated with an aggressive phenotype that may be adaptive to access host iron sources but which may also

CELF family RNA-binding protein UNC-75 regulates two sets of mutually exclusive exons of the unc-32 gene in neuron-specific manners in Caenorhabditis elegans.

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Hidehito Kuroyanagi

Full Text Available An enormous number of alternative pre-mRNA splicing patterns in multicellular organisms are coordinately defined by a limited number of regulatory proteins and cis elements. Mutually exclusive alternative splicing should be strictly regulated and is a challenging model for elucidating regulation mechanisms. Here we provide models of the regulation of two sets of mutually exclusive exons, 4a-4c and 7a-7b, of the Caenorhabditis elegans uncoordinated (unc-32 gene, encoding the a subunit of V0 complex of vacuolar-type H(+-ATPases. We visualize selection patterns of exon 4 and exon 7 in vivo by utilizing a trio and a pair of symmetric fluorescence splicing reporter minigenes, respectively, to demonstrate that they are regulated in tissue-specific manners. Genetic analyses reveal that RBFOX family RNA-binding proteins ASD-1 and FOX-1 and a UGCAUG stretch in intron 7b are involved in the neuron-specific selection of exon 7a. Through further forward genetic screening, we identify UNC-75, a neuron-specific CELF family RNA-binding protein of unknown function, as an essential regulator for the exon 7a selection. Electrophoretic mobility shift assays specify a short fragment in intron 7a as the recognition site for UNC-75 and demonstrate that UNC-75 specifically binds via its three RNA recognition motifs to the element including a UUGUUGUGUUGU stretch. The UUGUUGUGUUGU stretch in the reporter minigenes is actually required for the selection of exon 7a in the nervous system. We compare the amounts of partially spliced RNAs in the wild-type and unc-75 mutant backgrounds and raise a model for the mutually exclusive selection of unc-32 exon 7 by the RBFOX family and UNC-75. The neuron-specific selection of unc-32 exon 4b is also regulated by UNC-75 and the unc-75 mutation suppresses the Unc phenotype of the exon-4b-specific allele of unc-32 mutants. Taken together, UNC-75 is the neuron-specific splicing factor and regulates both sets of the mutually exclusive

Uniform approximation is more appropriate for Wilcoxon Rank-Sum Test in gene set analysis.

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Zhide Fang

Full Text Available Gene set analysis is widely used to facilitate biological interpretations in the analyses of differential expression from high throughput profiling data. Wilcoxon Rank-Sum (WRS test is one of the commonly used methods in gene set enrichment analysis. It compares the ranks of genes in a gene set against those of genes outside the gene set. This method is easy to implement and it eliminates the dichotomization of genes into significant and non-significant in a competitive hypothesis testing. Due to the large number of genes being examined, it is impractical to calculate the exact null distribution for the WRS test. Therefore, the normal distribution is commonly used as an approximation. However, as we demonstrate in this paper, the normal approximation is problematic when a gene set with relative small number of genes is tested against the large number of genes in the complementary set. In this situation, a uniform approximation is substantially more powerful, more accurate, and less intensive in computation. We demonstrate the advantage of the uniform approximations in Gene Ontology (GO term analysis using simulations and real data sets.

Comparative transcriptional profiling of the axolotl limb identifies a tripartite regeneration-specific gene program.

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Dunja Knapp

Full Text Available Understanding how the limb blastema is established after the initial wound healing response is an important aspect of regeneration research. Here we performed parallel expression profile time courses of healing lateral wounds versus amputated limbs in axolotl. This comparison between wound healing and regeneration allowed us to identify amputation-specific genes. By clustering the expression profiles of these samples, we could detect three distinguishable phases of gene expression - early wound healing followed by a transition-phase leading to establishment of the limb development program, which correspond to the three phases of limb regeneration that had been defined by morphological criteria. By focusing on the transition-phase, we identified 93 strictly amputation-associated genes many of which are implicated in oxidative-stress response, chromatin modification, epithelial development or limb development. We further classified the genes based on whether they were or were not significantly expressed in the developing limb bud. The specific localization of 53 selected candidates within the blastema was investigated by in situ hybridization. In summary, we identified a set of genes that are expressed specifically during regeneration and are therefore, likely candidates for the regulation of blastema formation.

Bacterial niche-specific genome expansion is coupled with highly frequent gene disruptions in deep-sea sediments

KAUST Repository

Wang, Yong; Yang, Jiang Ke; Lee, On On; Li, Tie Gang; Al-Suwailem, Abdulaziz M.; Danchin, Antoine; Qian, Pei-Yuan

2011-01-01

The complexity and dynamics of microbial metagenomes may be evaluated by genome size, gene duplication and the disruption rate between lineages. In this study, we pyrosequenced the metagenomes of microbes obtained from the brine and sediment of a deep-sea brine pool in the Red Sea to explore the possible genomic adaptations of the microbes in response to environmental changes. The microbes from the brine and sediments (both surface and deep layers) of the Atlantis II Deep brine pool had similar communities whereas the effective genome size varied from 7.4 Mb in the brine to more than 9 Mb in the sediment. This genome expansion in the sediment samples was due to gene duplication as evidenced by enrichment of the homologs. The duplicated genes were highly disrupted, on average by 47.6% and 70% for the surface and deep layers of the Atlantis II Deep sediment samples, respectively. The disruptive effects appeared to be mainly due to point mutations and frameshifts. In contrast, the homologs from the Atlantis II Deep brine sample were highly conserved and they maintained relatively small copy numbers. Likely, the adaptation of the microbes in the sediments was coupled with pseudogenizations and possibly functional diversifications of the paralogs in the expanded genomes. The maintenance of the pseudogenes in the large genomes is discussed. © 2011 Wang et al.

Bacterial niche-specific genome expansion is coupled with highly frequent gene disruptions in deep-sea sediments

KAUST Repository

Wang, Yong

2011-12-21

The complexity and dynamics of microbial metagenomes may be evaluated by genome size, gene duplication and the disruption rate between lineages. In this study, we pyrosequenced the metagenomes of microbes obtained from the brine and sediment of a deep-sea brine pool in the Red Sea to explore the possible genomic adaptations of the microbes in response to environmental changes. The microbes from the brine and sediments (both surface and deep layers) of the Atlantis II Deep brine pool had similar communities whereas the effective genome size varied from 7.4 Mb in the brine to more than 9 Mb in the sediment. This genome expansion in the sediment samples was due to gene duplication as evidenced by enrichment of the homologs. The duplicated genes were highly disrupted, on average by 47.6% and 70% for the surface and deep layers of the Atlantis II Deep sediment samples, respectively. The disruptive effects appeared to be mainly due to point mutations and frameshifts. In contrast, the homologs from the Atlantis II Deep brine sample were highly conserved and they maintained relatively small copy numbers. Likely, the adaptation of the microbes in the sediments was coupled with pseudogenizations and possibly functional diversifications of the paralogs in the expanded genomes. The maintenance of the pseudogenes in the large genomes is discussed. © 2011 Wang et al.

Bacterial niche-specific genome expansion is coupled with highly frequent gene disruptions in deep-sea sediments.

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Yong Wang

Full Text Available The complexity and dynamics of microbial metagenomes may be evaluated by genome size, gene duplication and the disruption rate between lineages. In this study, we pyrosequenced the metagenomes of microbes obtained from the brine and sediment of a deep-sea brine pool in the Red Sea to explore the possible genomic adaptations of the microbes in response to environmental changes. The microbes from the brine and sediments (both surface and deep layers of the Atlantis II Deep brine pool had similar communities whereas the effective genome size varied from 7.4 Mb in the brine to more than 9 Mb in the sediment. This genome expansion in the sediment samples was due to gene duplication as evidenced by enrichment of the homologs. The duplicated genes were highly disrupted, on average by 47.6% and 70% for the surface and deep layers of the Atlantis II Deep sediment samples, respectively. The disruptive effects appeared to be mainly due to point mutations and frameshifts. In contrast, the homologs from the Atlantis II Deep brine sample were highly conserved and they maintained relatively small copy numbers. Likely, the adaptation of the microbes in the sediments was coupled with pseudogenizations and possibly functional diversifications of the paralogs in the expanded genomes. The maintenance of the pseudogenes in the large genomes is discussed.

The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53.

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Flamini, Valentina; Ghadiali, Rachel S; Antczak, Philipp; Rothwell, Amy; Turnbull, Jeremy E; Pisconti, Addolorata

2018-03-13

Satellite cells are adult muscle stem cells residing in a specialized niche that regulates their homeostasis. How niche-generated signals integrate to regulate gene expression in satellite cell-derived myoblasts is poorly understood. We undertook an unbiased approach to study the effect of the satellite cell niche on satellite cell-derived myoblast transcriptional regulation and identified the tumor suppressor p53 as a key player in the regulation of myoblast quiescence. After activation and proliferation, a subpopulation of myoblasts cultured in the presence of the niche upregulates p53 and fails to differentiate. When satellite cell self-renewal is modeled ex vivo in a reserve cell assay, myoblasts treated with Nutlin-3, which increases p53 levels in the cell, fail to differentiate and instead become quiescent. Since both these Nutlin-3 effects are rescued by small interfering RNA-mediated p53 knockdown, we conclude that a tight control of p53 levels in myoblasts regulates the balance between differentiation and return to quiescence. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

An Automatic K-Means Clustering Algorithm of GPS Data Combining a Novel Niche Genetic Algorithm with Noise and Density

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Xiangbing Zhou

2017-12-01

Full Text Available Rapidly growing Global Positioning System (GPS data plays an important role in trajectory and their applications (e.g., GPS-enabled smart devices. In order to employ K-means to mine the better origins and destinations (OD behind the GPS data and overcome its shortcomings including slowness of convergence, sensitivity to initial seeds selection, and getting stuck in a local optimum, this paper proposes and focuses on a novel niche genetic algorithm (NGA with density and noise for K-means clustering (NoiseClust. In NoiseClust, an improved noise method and K-means++ are proposed to produce the initial population and capture higher quality seeds that can automatically determine the proper number of clusters, and also handle the different sizes and shapes of genes. A density-based method is presented to divide the number of niches, with its aim to maintain population diversity. Adaptive probabilities of crossover and mutation are also employed to prevent the convergence to a local optimum. Finally, the centers (the best chromosome are obtained and then fed into the K-means as initial seeds to generate even higher quality clustering results by allowing the initial seeds to readjust as needed. Experimental results based on taxi GPS data sets demonstrate that NoiseClust has high performance and effectiveness, and easily mine the city’s situations in four taxi GPS data sets.

The niche party concept and its measurement.

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Meyer, Thomas M; Miller, Bernhard

2015-03-01

The concept of the niche party has become increasingly popular in analyses of party competition. Yet, existing approaches vary in their definitions and their measurement approaches. We propose using a minimal definition that allows us to compare political parties in terms of their 'nicheness'. We argue that the conceptual core of the niche party concept is based on issue emphasis and that a niche party emphasizes policy areas neglected by its rivals. Based on this definition, we propose a continuous measure that allows for more fine-grained measurement of a party's 'nicheness' than the dominant, dichotomous approaches and thereby limits the risk of measurement error. Drawing on data collected by the Comparative Manifesto Project, we show that (1) our measure has high face validity and (2) exposes differences among parties that are not captured by alternative, static or dichotomous measures.

The evolution of climatic niches in squamate reptiles.

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Pie, Marcio R; Campos, Leonardo L F; Meyer, Andreas L S; Duran, Andressa

2017-07-12

Despite the remarkable diversity found in squamate reptiles, most of their species tend to be found in warm/dry environments, suggesting that climatic requirements played a crucial role in their diversification, yet little is known about the evolution of their climatic niches. In this study, we integrate climatic information associated with the geographical distribution of 1882 squamate species and their phylogenetic relationships to investigate the tempo and mode of climatic niche evolution in squamates, both over time and among lineages. We found that changes in climatic niche dynamics were pronounced over their recent squamate evolutionary history, and we identified extensive evidence for rate heterogeneity in squamate climatic niche evolution. Most rate shifts involved accelerations, particularly over the past 50 Myr. Most squamates occupy similar regions of the climatic niche space, with only a few lineages diversifying into colder and humid climatic conditions. The changes from arid to mesic conditions in some regions of the globe may have provided opportunities for climatic niche evolution, although most lineages tended to remain near their ancestral niche. Variation in rates of climatic niche evolution seems common, particularly in response to the availability of new climatic conditions over evolutionary time. © 2017 The Author(s).

Multifaceted Roles of Connexin 43 in Stem Cell Niches.

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Genet, Nafiisha; Bhatt, Neha; Bourdieu, Antonin; Hirschi, Karen K

2018-01-01

Considerable progress has been made in the field of stem cell research; nonetheless, the use of stem cells for regenerative medicine therapies, for either endogenous tissue repair or cellular grafts post injury, remains a challenge. To better understand how to maintain stem cell potential in vivo and promote differentiation ex vivo, it is fundamentally important to elucidate the interactions between stem cells and their surrounding partners within their distinct niches. Among the vast array of proteins depicted as mediators for cell-to-cell interactions, connexin-comprised gap junctions play pivotal roles in the regulation of stem cell fate both in vivo and in vitro. This review summarizes and illustrates the current knowledge regarding the multifaceted roles of Cx43, specifically, in various stem cell niches.

Prospects for Jatropha biofuels in Tanzania: An analysis with Strategic Niche Management

International Nuclear Information System (INIS)

Eijck, Janske van; Romijn, Henny

2008-01-01

The paper reports on research in Tanzania about the scope for developing biofuels from an oil-seed bearing plant called Jatropha curcas Linnaeus. The plant is widely seen to have potential to help combat the greenhouse effect, help to stop local soil erosion, create additional income for the rural poor, and provide a major source of energy both locally and internationally. The principal analytic tool is Strategic Niche Management (SNM), an approach rooted in evolutionary innovation theory. We analyse how the scope for an energy transition is influenced by factors at three societal levels: the overarching 'landscape'; the sectoral setting or 'regime'; and the 'niche' level where the innovation develops and diffuses. Valuable niche processes were found in a few areas, especially in cultivation, but we conclude that there are still many obstacles in Tanzania's prevailing energy regime. The development of Jatropha biofuels is still in an early phase. We list policy recommendations and discuss some methodological issues arising from the use of SNM

Manipulation of signaling thresholds in "engineered stem cell niches" identifies design criteria for pluripotent stem cell screens.

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Raheem Peerani

Full Text Available In vivo, stem cell fate is regulated by local microenvironmental parameters. Governing parameters in this stem cell niche include soluble factors, extra-cellular matrix, and cell-cell interactions. The complexity of this in vivo niche limits analyses into how individual niche parameters regulate stem cell fate. Herein we use mouse embryonic stem cells (mESC and micro-contact printing (microCP to investigate how niche size controls endogenous signaling thresholds. microCP is used to restrict colony diameter, separation, and degree of clustering. We show, for the first time, spatial control over the activation of the Janus kinase/signal transducer and activator of transcription pathway (Jak-Stat. The functional consequences of this niche-size-dependent signaling control are confirmed by demonstrating that direct and indirect transcriptional targets of Stat3, including members of the Jak-Stat pathway and pluripotency-associated genes, are regulated by colony size. Modeling results and empirical observations demonstrate that colonies less than 100 microm in diameter are too small to maximize endogenous Stat3 activation and that colonies separated by more than 400 microm can be considered independent from each other. These results define parameter boundaries for the use of ESCs in screening studies, demonstrate the importance of context in stem cell responsiveness to exogenous cues, and suggest that niche size is an important parameter in stem cell fate control.

Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche

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Kapp, Friedrich G.; Perlin, Julie R.; Hagedorn, Elliott J.; Gansner, John M.; Schwarz, Daniel E.; O'Connell, Lauren A.; Johnson, Nicholas; Amemiya, Chris; Fisher, David E.; Wolfle, Ute; Trompouki, Eirini; Niemeyer, Charlotte M.; Driever, Wolfgang; Zon, Leonard I.

2018-01-01

Haematopoietic stem and progenitor cells (HSPCs) require a specific microenvironment, the haematopoietic niche, which regulates HSPC behaviour. The location of this niche varies across species, but the evolutionary pressures that drive HSPCs to different microenvironments remain unknown. The niche is located in the bone marrow in adult mammals, whereas it is found in other locations in non-mammalian vertebrates, for example, in the kidney marrow in teleost fish. Here we show that a melanocyte umbrella above the kidney marrow protects HSPCs against ultraviolet light in zebrafish. Because mutants that lack melanocytes have normal steady-state haematopoiesis under standard laboratory conditions, we hypothesized that melanocytes above the stem cell niche protect HSPCs against ultraviolet-light-induced DNA damage. Indeed, after ultraviolet-light irradiation, unpigmented larvae show higher levels of DNA damage in HSPCs, as indicated by staining of cyclobutane pyrimidine dimers and have reduced numbers of HSPCs, as shown by cmyb (also known as myb) expression. The umbrella of melanocytes associated with the haematopoietic niche is highly evolutionarily conserved in aquatic animals, including the sea lamprey, a basal vertebrate. During the transition from an aquatic to a terrestrial environment, HSPCs relocated into the bone marrow, which is protected from ultraviolet light by the cortical bone around the marrow. Our studies reveal that melanocytes above the haematopoietic niche protect HSPCs from ultraviolet-light-induced DNA damage in aquatic vertebrates and suggest that during the transition to terrestrial life, ultraviolet light was an evolutionary pressure affecting the location of the haematopoietic niche.

The HysNiche trial: hysteroscopic resection of uterine caesarean scar defect (niche) in patients with abnormal bleeding, a randomised controlled trial.

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Vervoort, A J M W; Van der Voet, L F; Witmer, M; Thurkow, A L; Radder, C M; van Kesteren, P J M; Quartero, H W P; Kuchenbecker, W K H; Bongers, M Y; Geomini, P M A J; de Vleeschouwer, L H M; van Hooff, M H A; van Vliet, H A A M; Veersema, S; Renes, W B; van Meurs, H S; Bosmans, J; Oude Rengerink, K; Brölmann, H A M; Mol, B W J; Huirne, J A F

2015-11-12

A caesarean section (CS) can cause a defect or disruption of the myometrium at the site of the uterine scar, called a niche. In recent years, an association between a niche and postmenstrual spotting after a CS has been demonstrated. Hysteroscopic resection of these niches is thought to reduce spotting and menstrual pain. However, there are no randomised trials assessing the effectiveness of a hysteroscopic niche resection. We planned a multicentre randomised trial comparing hysteroscopic niche resection to no intervention. We study women with postmenstrual spotting after a CS and a niche with a residual myometrium of at least 3 mm during sonohysterography. After informed consent is obtained, eligible women will be randomly allocated to hysteroscopic resection of the niche or expectant management for 6 months. The primary outcome is the number of days with postmenstrual spotting during one menstrual cycle 6 months after randomisation. Secondary outcomes are menstrual characteristics, menstruation related pain and experienced discomfort due to spotting or menstrual pain, quality of life, patient satisfaction, sexual function, urological symptoms, medical consultations, medication use, complications, lost productivity and medical costs. Measurements will be performed at baseline and at 3 and 6 months after randomisation. A cost-effectiveness analysis will be performed from a societal perspective at 6 months after randomisation. This trial will provide insight in the (cost)effectiveness of hysteroscopic resection of a niche versus expectant management in women who have postmenstrual spotting and a niche with sufficient residual myometrium to perform a hysteroscopic niche resection. Dutch Trial Register NTR3269 . Registered 1 February 2012. ZonMw Grant number 80-82305-97-12030.

Identification of ecotype-specific marker genes for categorization of beer-spoiling Lactobacillus brevis.

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Behr, Jürgen; Geissler, Andreas J; Preissler, Patrick; Ehrenreich, Armin; Angelov, Angel; Vogel, Rudi F

2015-10-01

The tolerance to hop compounds, which is mainly associated with inhibition of bacterial growth in beer, is a multi-factorial trait. Any approaches to predict the physiological differences between beer-spoiling and non-spoiling strains on the basis of a single marker gene are limited. We identified ecotype-specific genes related to the ability to grow in Pilsner beer via comparative genome sequencing. The genome sequences of four different strains of Lactobacillus brevis were compared, including newly established genomes of two highly hop tolerant beer isolates, one strain isolated from faeces and one published genome of a silage isolate. Gene fragments exclusively occurring in beer-spoiling strains as well as sequences only occurring in non-spoiling strains were identified. Comparative genomic arrays were established and hybridized with a set of L. brevis strains, which are characterized by their ability to spoil beer. As result, a set of 33 and 4 oligonucleotide probes could be established specifically detecting beer-spoilers and non-spoilers, respectively. The detection of more than one of these marker sequences according to a genetic barcode enables scoring of L. brevis for their beer-spoiling potential and can thus assist in risk evaluation in brewing industry. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Environmental Acinetobacter baumannii Isolate DSM30011 Reveals Clues into the Preantibiotic Era Genome Diversity, Virulence Potential, and Niche Range of a Predominant Nosocomial Pathogen

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Viale, Alejandro M.; Borges, Vítor; Cameranesi, María M.; Taib, Najwa; Espariz, Martín; Brochier-Armanet, Céline; Gomes, João Paulo; Salcedo, Suzana P.

2017-01-01

Abstract Acinetobacter baumannii represents nowadays an important nosocomial opportunistic pathogen whose reservoirs outside the clinical setting are obscure. Here, we traced the origins of the collection strain A. baumannii DSM30011 to an isolate first reported in 1944, obtained from the enriched microbiota responsible of the aerobic decomposition of the resinous desert shrub guayule. Whole-genome sequencing and phylogenetic analysis based on core genes confirmed DSM30011 affiliation to A. baumannii. Comparative studies with 32 complete A. baumannii genomes revealed the presence of 12 unique accessory chromosomal regions in DSM30011 including five encompassing phage-related genes, five containing toxin genes of the type-6 secretion system, and one with an atypical CRISPRs/cas cluster. No antimicrobial resistance islands were identified in DSM30011 agreeing with a general antimicrobial susceptibility phenotype including folate synthesis inhibitors. The marginal ampicillin resistance of DSM30011 most likely derived from chromosomal ADC-type ampC and blaOXA-51-type genes. Searching for catabolic pathways genes revealed several clusters involved in the degradation of plant defenses including woody tissues and a previously unreported atu locus responsible of aliphatic terpenes degradation, thus suggesting that resinous plants may provide an effective niche for this organism. DSM30011 also harbored most genes and regulatory mechanisms linked to persistence and virulence in pathogenic Acinetobacter species. This strain thus revealed important clues into the genomic diversity, virulence potential, and niche ranges of the preantibiotic era A. baumannii population, and may provide an useful tool for our understanding of the processes that led to the recent evolution of this species toward an opportunistic pathogen of humans. PMID:28934377

Oral treponeme major surface protein: Sequence diversity and distributions within periodontal niches.

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You, M; Chan, Y; Lacap-Bugler, D C; Huo, Y-B; Gao, W; Leung, W K; Watt, R M

2017-12-01

Treponema denticola and other species (phylotypes) of oral spirochetes are widely considered to play important etiological roles in periodontitis and other oral infections. The major surface protein (Msp) of T. denticola is directly implicated in several pathological mechanisms. Here, we have analyzed msp sequence diversity across 68 strains of oral phylogroup 1 and 2 treponemes; including reference strains of T. denticola, Treponema putidum, Treponema medium, 'Treponema vincentii', and 'Treponema sinensis'. All encoded Msp proteins contained highly conserved, taxon-specific signal peptides, and shared a predicted 'three-domain' structure. A clone-based strategy employing 'msp-specific' polymerase chain reaction primers was used to analyze msp gene sequence diversity present in subgingival plaque samples collected from a group of individuals with chronic periodontitis (n=10), vs periodontitis-free controls (n=10). We obtained 626 clinical msp gene sequences, which were assigned to 21 distinct 'clinical msp genotypes' (95% sequence identity cut-off). The most frequently detected clinical msp genotype corresponded to T. denticola ATCC 35405 T , but this was not correlated to disease status. UniFrac and libshuff analysis revealed that individuals with periodontitis and periodontitis-free controls harbored significantly different communities of treponeme clinical msp genotypes (Pdiversity than periodontitis-free controls (Mann-Whitney U-test, Pdiversity of Treponema clinical msp genotypes within their subgingival niches. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Simultaneous inference of phenotype-associated genes and relevant tissues from GWAS data via Bayesian integration of multiple tissue-specific gene networks.

Science.gov (United States)

Wu, Mengmeng; Lin, Zhixiang; Ma, Shining; Chen, Ting; Jiang, Rui; Wong, Wing Hung

2017-12-01

Although genome-wide association studies (GWAS) have successfully identified thousands of genomic loci associated with hundreds of complex traits in the past decade, the debate about such problems as missing heritability and weak interpretability has been appealing for effective computational methods to facilitate the advanced analysis of the vast volume of existing and anticipated genetic data. Towards this goal, gene-level integrative GWAS analysis with the assumption that genes associated with a phenotype tend to be enriched in biological gene sets or gene networks has recently attracted much attention, due to such advantages as straightforward interpretation, less multiple testing burdens, and robustness across studies. However, existing methods in this category usually exploit non-tissue-specific gene networks and thus lack the ability to utilize informative tissue-specific characteristics. To overcome this limitation, we proposed a Bayesian approach called SIGNET (Simultaneously Inference of GeNEs and Tissues) to integrate GWAS data and multiple tissue-specific gene networks for the simultaneous inference of phenotype-associated genes and relevant tissues. Through extensive simulation studies, we showed the effectiveness of our method in finding both associated genes and relevant tissues for a phenotype. In applications to real GWAS data of 14 complex phenotypes, we demonstrated the power of our method in both deciphering genetic basis and discovering biological insights of a phenotype. With this understanding, we expect to see SIGNET as a valuable tool for integrative GWAS analysis, thereby boosting the prevention, diagnosis, and treatment of human inherited diseases and eventually facilitating precision medicine.

Identification of a robust gene signature that predicts breast cancer outcome in independent data sets

International Nuclear Information System (INIS)

Korkola, James E; Waldman, Frederic M; Blaveri, Ekaterina; DeVries, Sandy; Moore, Dan H II; Hwang, E Shelley; Chen, Yunn-Yi; Estep, Anne LH; Chew, Karen L; Jensen, Ronald H

2007-01-01

Breast cancer is a heterogeneous disease, presenting with a wide range of histologic, clinical, and genetic features. Microarray technology has shown promise in predicting outcome in these patients. We profiled 162 breast tumors using expression microarrays to stratify tumors based on gene expression. A subset of 55 tumors with extensive follow-up was used to identify gene sets that predicted outcome. The predictive gene set was further tested in previously published data sets. We used different statistical methods to identify three gene sets associated with disease free survival. A fourth gene set, consisting of 21 genes in common to all three sets, also had the ability to predict patient outcome. To validate the predictive utility of this derived gene set, it was tested in two published data sets from other groups. This gene set resulted in significant separation of patients on the basis of survival in these data sets, correctly predicting outcome in 62–65% of patients. By comparing outcome prediction within subgroups based on ER status, grade, and nodal status, we found that our gene set was most effective in predicting outcome in ER positive and node negative tumors. This robust gene selection with extensive validation has identified a predictive gene set that may have clinical utility for outcome prediction in breast cancer patients

Gene Acquisition Convergence between Entomopoxviruses and Baculoviruses

Directory of Open Access Journals (Sweden)

Julien Thézé

2015-04-01

Full Text Available Organisms from diverse phylogenetic origins can thrive within the same ecological niches. They might be induced to evolve convergent adaptations in response to a similar landscape of selective pressures. Their genomes should bear the signature of this process. The study of unrelated virus lineages infecting the same host panels guarantees a clear identification of phyletically independent convergent adaptation. Here, we investigate the evolutionary history of genes in the accessory genome shared by unrelated insect large dsDNA viruses: the entomopoxviruses (EPVs, Poxviridae and the baculoviruses (BVs. EPVs and BVs have overlapping ecological niches and have independently evolved similar infection processes. They are, in theory, subjected to the same selective pressures from their host’s immune responses. Their accessory genomes might, therefore, bear analogous genomic signatures of convergent adaption and could point out key genomic mechanisms of adaptation hitherto undetected in viruses. We uncovered 32 homologous, yet independent acquisitions of genes originating from insect hosts, different eukaryotes, bacteria and viruses. We showed different evolutionary levels of gene acquisition convergence in these viruses, underlining a continuous evolutionary process. We found both recent and ancient gene acquisitions possibly involved to the adaptation to both specific and distantly related hosts. Multidirectional and multipartite gene exchange networks appear to constantly drive exogenous gene assimilations, bringing key adaptive innovations and shaping the life histories of large DNA viruses. This evolutionary process might lead to genome level adaptive convergence.

Niche acclimatization in Red Sea corals is dependent on flexibility of host-symbiont association

KAUST Repository

Ziegler, Maren; Roder, Cornelia; Bü chel, C; Voolstra, Christian R.

2015-01-01

Knowledge of host-symbiont specificity and acclimatization capacity of corals is crucial for understanding implications of environmental change. Whilst some corals have been shown to associate with a number of symbionts that may comprise different physiologies, most corals associate with only one dominant Symbiodinium species at a time. Coral communities in the Red Sea thrive under large fluctuations of environmental conditions, but the degree and mechanisms of coral acclimatization are largely unexplored. Here we investigated the potential for niche acclimatization in 2 dominant corals from the central Red Sea, Pocillopora verrucosa and Porites lutea, in relation to the fidelity of the underlying coral-symbiont association. Repeated sampling over 2 seasons along a cross-shelf and depth gradient revealed a stable symbiont association in P. verrucosa and flexible association in P. lutea. A statistical biological-environmental matching routine revealed that the high plasticity of photophysiology and photopigments in the stable Symbiodinium microadriaticum (type A1) community in P. verrucosa were correlated with environmental influences along spatio-temporal dimensions. In contrast, photophysiology and pigments were less variable within each symbiont type from P. lutea indicating that niche acclimatization was rather regulated by a flexible association with a variable Symbiodinium community. Based on these data, we advocate an extended concept of phenotypic plasticity of the coral holobiont, in which the scleractinian host either associates with a specific Symbiodinium type with a broad physiological tolerance, or the host-symbiont pairing is more flexible to accommodate for different symbiont associations, each adapted to specific environmental settings.

Niche acclimatization in Red Sea corals is dependent on flexibility of host-symbiont association

KAUST Repository

Ziegler, Maren

2015-08-06

Knowledge of host-symbiont specificity and acclimatization capacity of corals is crucial for understanding implications of environmental change. Whilst some corals have been shown to associate with a number of symbionts that may comprise different physiologies, most corals associate with only one dominant Symbiodinium species at a time. Coral communities in the Red Sea thrive under large fluctuations of environmental conditions, but the degree and mechanisms of coral acclimatization are largely unexplored. Here we investigated the potential for niche acclimatization in 2 dominant corals from the central Red Sea, Pocillopora verrucosa and Porites lutea, in relation to the fidelity of the underlying coral-symbiont association. Repeated sampling over 2 seasons along a cross-shelf and depth gradient revealed a stable symbiont association in P. verrucosa and flexible association in P. lutea. A statistical biological-environmental matching routine revealed that the high plasticity of photophysiology and photopigments in the stable Symbiodinium microadriaticum (type A1) community in P. verrucosa were correlated with environmental influences along spatio-temporal dimensions. In contrast, photophysiology and pigments were less variable within each symbiont type from P. lutea indicating that niche acclimatization was rather regulated by a flexible association with a variable Symbiodinium community. Based on these data, we advocate an extended concept of phenotypic plasticity of the coral holobiont, in which the scleractinian host either associates with a specific Symbiodinium type with a broad physiological tolerance, or the host-symbiont pairing is more flexible to accommodate for different symbiont associations, each adapted to specific environmental settings.

A Bayesian variable selection procedure for ranking overlapping gene sets

DEFF Research Database (Denmark)

Skarman, Axel; Mahdi Shariati, Mohammad; Janss, Luc

2012-01-01

Background Genome-wide expression profiling using microarrays or sequence-based technologies allows us to identify genes and genetic pathways whose expression patterns influence complex traits. Different methods to prioritize gene sets, such as the genes in a given molecular pathway, have been de...

Ecological niche differentiation of polyploidization is not supported by environmental differences among species in a cosmopolitan grass genus.

Science.gov (United States)

Visser, Vernon; Molofsky, Jane

2015-01-01

• Polyploidization frequently results in the creation of new plant species, the establishment of which is thought to often be facilitated by ecological niche differentiation from the diploid species. We tested this hypothesis using the cosmopolitan grass genus Phalaris (Poaceae), consisting of 19 species that range from diploid to tetraploid to hexaploid. Specifically, we tested whether (1) polyploids occupy more extreme environments and/or (2) have broader niche breadths and/or (3) whether the polyploid species' distributions indicate a niche shift from diploid species.• We employed a bootstrapping approach using distribution data for each species and eight environmental variables to investigate differences between species in the means, extremes, and breadths of each environmental variable. We used a kernel smoothing technique to quantify niche overlap between species.• Although we found some support for the three hypotheses for a few diploid-polyploid pairs and for specific environmental variables, none of these hypotheses were generally supported.• Our results suggest that these commonly held hypotheses about the effects of polyploidization on ecological distributions are not universally applicable. Correlative biogeographic studies like ours provide a necessary first step for suggesting specific hypotheses that require experimental verification. A combination of genetic, physiological, and ecological studies will be required to achieve a better understanding of the role of polyploidization in niche evolution. © 2015 Botanical Society of America, Inc.

Delimiting Coalescence Genes (C-Genes) in Phylogenomic Data Sets.

Science.gov (United States)

Springer, Mark S; Gatesy, John

2018-02-26

coalescence methods have emerged as a popular alternative for inferring species trees with large genomic datasets, because these methods explicitly account for incomplete lineage sorting. However, statistical consistency of summary coalescence methods is not guaranteed unless several model assumptions are true, including the critical assumption that recombination occurs freely among but not within coalescence genes (c-genes), which are the fundamental units of analysis for these methods. Each c-gene has a single branching history, and large sets of these independent gene histories should be the input for genome-scale coalescence estimates of phylogeny. By contrast, numerous studies have reported the results of coalescence analyses in which complete protein-coding sequences are treated as c-genes even though exons for these loci can span more than a megabase of DNA. Empirical estimates of recombination breakpoints suggest that c-genes may be much shorter, especially when large clades with many species are the focus of analysis. Although this idea has been challenged recently in the literature, the inverse relationship between c-gene size and increased taxon sampling in a dataset-the 'recombination ratchet'-is a fundamental property of c-genes. For taxonomic groups characterized by genes with long intron sequences, complete protein-coding sequences are likely not valid c-genes and are inappropriate units of analysis for summary coalescence methods unless they occur in recombination deserts that are devoid of incomplete lineage sorting (ILS). Finally, it has been argued that coalescence methods are robust when the no-recombination within loci assumption is violated, but recombination must matter at some scale because ILS, a by-product of recombination, is the raison d'etre for coalescence methods. That is, extensive recombination is required to yield the large number of independently segregating c-genes used to infer a species tree. If coalescent methods are powerful

Deregulation of epidermal stem cell niche contributes to pathogenesis of non-healing venous ulcers

Science.gov (United States)

Nusbaum, Aron G.; Vukelic, Sasa; Krzyzanowska, Agata; Tomic-Canic, Marjana

2014-01-01

The epidermis is maintained by epidermal stem cells (ESC) that reside in distinct niches and contribute to homeostasis and wound closure. Keratinocytes at the non-healing edges of venous ulcers (VUs) are healing-incompetent, hyper-proliferative and non-migratory suggesting deregulation of ESCs. To date genes which regulate ESC niches have been studied in mice only. Utilizing microarray analysis of VU non-healing edges, we identified changes in expression of genes harboring regulation of ESCs and their fate. In a prospective clinical study of ten VUs, we confirmed suppression of the bone morphogenetic protein receptor and GATA binding protein3 as well as inhibitors of DNA-binding proteins 2 and 4. We also found decreased levels of phosphorylated glycogen synthase kinase 3, nuclear presence of ß-catenin and overexpression of its transcriptional target, c-myc indicating activation of the Wnt pathway. Additionally, we found down-regulation of leucine-rich repeats and immunoglobulin-like domains protein 1, a gene important for maintaining ESCs in a quiescent state, and absence of keratin 15, a marker of the basal stem cell compartment suggesting local depletion of ESCs. Our study shows that loss of genes important for regulation of ESCs and their fate along with activation of ß-catenin and c-myc in the VU may contribute to ESC deprivation and a hyper-proliferative, non-migratory, healing incapable wound edge. PMID:24635172

An Independent Filter for Gene Set Testing Based on Spectral Enrichment

NARCIS (Netherlands)

Frost, H Robert; Li, Zhigang; Asselbergs, Folkert W; Moore, Jason H

2015-01-01

Gene set testing has become an indispensable tool for the analysis of high-dimensional genomic data. An important motivation for testing gene sets, rather than individual genomic variables, is to improve statistical power by reducing the number of tested hypotheses. Given the dramatic growth in

Secreted protein Del-1 regulates myelopoiesis in the hematopoietic stem cell niche.

Science.gov (United States)

Mitroulis, Ioannis; Chen, Lan-Sun; Singh, Rashim Pal; Kourtzelis, Ioannis; Economopoulou, Matina; Kajikawa, Tetsuhiro; Troullinaki, Maria; Ziogas, Athanasios; Ruppova, Klara; Hosur, Kavita; Maekawa, Tomoki; Wang, Baomei; Subramanian, Pallavi; Tonn, Torsten; Verginis, Panayotis; von Bonin, Malte; Wobus, Manja; Bornhäuser, Martin; Grinenko, Tatyana; Di Scala, Marianna; Hidalgo, Andres; Wielockx, Ben; Hajishengallis, George; Chavakis, Triantafyllos

2017-10-02

Hematopoietic stem cells (HSCs) remain mostly quiescent under steady-state conditions but switch to a proliferative state following hematopoietic stress, e.g., bone marrow (BM) injury, transplantation, or systemic infection and inflammation. The homeostatic balance between quiescence, self-renewal, and differentiation of HSCs is strongly dependent on their interactions with cells that constitute a specialized microanatomical environment in the BM known as the HSC niche. Here, we identified the secreted extracellular matrix protein Del-1 as a component and regulator of the HSC niche. Specifically, we found that Del-1 was expressed by several cellular components of the HSC niche, including arteriolar endothelial cells, CXCL12-abundant reticular (CAR) cells, and cells of the osteoblastic lineage. Del-1 promoted critical functions of the HSC niche, as it regulated long-term HSC (LT-HSC) proliferation and differentiation toward the myeloid lineage. Del-1 deficiency in mice resulted in reduced LT-HSC proliferation and infringed preferentially upon myelopoiesis under both steady-state and stressful conditions, such as hematopoietic cell transplantation and G-CSF- or inflammation-induced stress myelopoiesis. Del-1-induced HSC proliferation and myeloid lineage commitment were mediated by β3 integrin on hematopoietic progenitors. This hitherto unknown Del-1 function in the HSC niche represents a juxtacrine homeostatic adaptation of the hematopoietic system in stress myelopoiesis.

[Mesenchymal stroma cells and their niche].

Science.gov (United States)

Schneider, R K

2013-11-01

Stem cells reside in a highly specialized, complex microenvironment that is known as the stem cell niche. The stem cell niche can be described as an anatomically defined space where the stem cell is localized and nourished and stem cell quiescence, proliferation and differentiation are maintained. Tissue engineering aims to imitate the stem cell niche to (I) induce a directed differentiation, (II) maintain the self-renewal capacity or (III) find a regulated balance between self-renewal and differentiation. Mesenchymal stem or stromal cells (MSC) can differentiate in three-dimensional collagen gels into functional osteoblasts when subjected to a phosphate-rich cultivation medium. Furthermore, they acquire a prosynthetic, matrix remodeling, contractile phenotype. Medial artery calcification in patients with chronic kidney disease also proceeds through intramembranous ossification resulting from osteoblast-induced calcification of the collagen extracellular matrix. Thus, the influence of uremic cultivation conditions as a pathophysiological stimulus on MSC and endothelial cells was analyzed with special regards to matrix remodeling, vascularization and calcification. The results showed that BMP-2/4 mediated MSC (mal)differentiation into osteoblasts with acquired matrix remodeling phenotype and loss of proangiogenic capacity. These studies have led to the conclusion that uremia has detrimental effects on the stem cell niche and promotes the continuous calcification by osteogenic (mal)differentiation. In summary, recent studies have shown the conducting and regulating effect of the stem cell niche under physiological conditions that can be applied and mimicked for tissue engineering applications. However, under pathological conditions the stem cell niche can have detrimental effects on stem cell function and can promote disease progression.

Mates but not sexes differ in migratory niche in a monogamous penguin species.

Science.gov (United States)

Thiebot, Jean-Baptiste; Bost, Charles-André; Dehnhard, Nina; Demongin, Laurent; Eens, Marcel; Lepoint, Gilles; Cherel, Yves; Poisbleau, Maud

2015-09-01

Strong pair bonds generally increase fitness in monogamous organisms, but may also underlie the risk of hampering it when re-pairing fails after the winter season. We investigated whether partners would either maintain contact or offset this risk by exploiting sex-specific favourable niches during winter in a migratory monogamous seabird, the southern rockhopper penguin Eudyptes chrysocome. Using light-based geolocation, we show that although the spatial distribution of both sexes largely overlapped, pair-wise mates were located on average 595 ± 260 km (and up to 2500 km) apart during winter. Stable isotope data also indicated a marked overlap between sex-specific isotopic niches (δ¹³C and δ¹⁵N values) but a segregation of the feeding habitats (δ¹³C values) within pairs. Importantly, the tracked females remained longer (12 days) at sea than males, but all re-mated with their previous partners after winter. Our study provides multiple evidence that migratory species may well demonstrate pair-wise segregation even in the absence of sex-specific winter niches (spatial and isotopic). We suggest that dispersive migration patterns with sex-biased timings may be a sufficient proximal cause for generating such a situation in migratory animals.

Model-based gene set analysis for Bioconductor.

Science.gov (United States)

Bauer, Sebastian; Robinson, Peter N; Gagneur, Julien

2011-07-01

Gene Ontology and other forms of gene-category analysis play a major role in the evaluation of high-throughput experiments in molecular biology. Single-category enrichment analysis procedures such as Fisher's exact test tend to flag large numbers of redundant categories as significant, which can complicate interpretation. We have recently developed an approach called model-based gene set analysis (MGSA), that substantially reduces the number of redundant categories returned by the gene-category analysis. In this work, we present the Bioconductor package mgsa, which makes the MGSA algorithm available to users of the R language. Our package provides a simple and flexible application programming interface for applying the approach. The mgsa package has been made available as part of Bioconductor 2.8. It is released under the conditions of the Artistic license 2.0. peter.robinson@charite.de; julien.gagneur@embl.de.

Gene set analysis for interpreting genetic studies

DEFF Research Database (Denmark)

Pers, Tune H

2016-01-01

Interpretation of genome-wide association study (GWAS) results is lacking behind the discovery of new genetic associations. Consequently, there is an urgent need for data-driven methods for interpreting genetic association studies. Gene set analysis (GSA) can identify aetiologic pathways...

Vascular and perivascular niches, but not the osteoblastic niche, are numerically restored following allogeneic hematopoietic stem cell transplantation in patients with aplastic anemia.

Science.gov (United States)

Wu, Liangliang; Mo, Wenjian; Zhang, Yuping; Zhou, Ming; Li, Yumiao; Zhou, Ruiqing; Xu, Shiling; Pan, Shiyi; Deng, Hui; Mao, Ping; Wang, Shunqing

2017-07-01

Bone marrow (BM) niches, including the osteoblastic, vascular, and perivascular niches, are numerically impaired in patients with aplastic anemia (AA). It remains unclear whether these niches are numerically restored in AA patients after allogenic hematopoietic stem cell transplantation (allo-HSCT). To investigate changes in BM niches, we monitored 52 patients with AA who had undergone allo-HSCT and performed immunohistochemical studies of BM niches using antibodies against CD34, CD146, and osteopontin. After allo-HSCT, patients with AA exhibited a remarkable increase in the number of cellular elements in the BM niches, including the vascular and perivascular cells. However, no significant differences in endosteal cells were detected. We explored the cause of this restoration by analyzing the origin of BM mesenchymal stem cells (BM-MSCs) and the expression of cytokines in BM plasma. STR-PCR revealed that the BM-MSCs were derived from the host, not the donor. In addition, significantly elevated levels of vascular endothelial growth factor (VEGF) were found after allo-HSCT. Our data indicates that vascular and perivascular niches are numerically restored, but the endosteal niche remains numerically impaired in patients with AA after allo-HSCT, and that levels of VEGF, but not donor-derived BM-MSCs, may correlate with the restoration of BM niches.

A GRFa2/Prop1/stem (GPS) cell niche in the pituitary.

Science.gov (United States)

Garcia-Lavandeira, Montse; Quereda, Víctor; Flores, Ignacio; Saez, Carmen; Diaz-Rodriguez, Esther; Japon, Miguel A; Ryan, Aymee K; Blasco, Maria A; Dieguez, Carlos; Malumbres, Marcos; Alvarez, Clara V

2009-01-01

The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the pituitary gland throughout life as well as

Classification and comparison of niche services for developing strategy of medical tourism in Asian countries.

Science.gov (United States)

Chen, Hung-chi; Kuo, Hsin-chih; Chung, Kuo-Piao; Chang, Sophia; Su, Syi; Yang, Ming-chin

2010-01-01

Medical tourism is a new trend in medical service. It is booming not only in Asian countries but also in European and South American countries. Worldwide competition of medical service is expected in the future, and niche service will be a "trademark" for the promotion of global medicine. Niche service also functions for market segmentation. Niche services are usually surgical procedures. A study was carried out to compare different strategies for developing medical tourism in Asian countries. The role of a niche service is evaluated in the initiation and further development of medical tourism for individual countries. From this study, a general classification was proposed in terms of treatment procedures. It can be used as a useful guideline for additional studies in medical tourism. Niche service plays the following roles in the development of medical tourism: (1) It attracts attention in the mass media and helps in subsequent promotion of business, (2) it exerts pressure on the hospital, which must improve the quality of health care provided in treating foreign patients, especially the niche services, and (3) it is a tool for setting up the business model. E-Da Hospital is an example for developing medical tourism in Taiwan. A side effect is that niche service brings additional foreign patients, which will contribute to the benefit of the hospital, but this leaves less room for treating domestic patients. A niche service is a means of introduction for entry into the market of medical tourism. How to create a successful story is important for the development of a niche service. When a good reputation has been established, the information provided on the Internet can last for a long time and can spread internationally to form a distinguished mark for further development. Niche services can be classified into 3 categories: (1) Low-risk procedures with large price differences and long stay after retirement; (2) high-risk procedures with less of a price difference

Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron Subtypes

Directory of Open Access Journals (Sweden)

Leon French

2017-05-01

Full Text Available Genome-wide expression profiling of the human brain has revealed genes that are differentially expressed across the lifespan. Characterizing these genes adds to our understanding of both normal functions and pathological conditions. Additionally, the specific cell-types that contribute to the motor, sensory and cognitive declines during aging are unclear. Here we test if age-related genes show higher expression in specific neural cell types. Our study leverages data from two sources of murine single-cell expression data and two sources of age-associations from large gene expression studies of postmortem human brain. We used nonparametric gene set analysis to test for age-related enrichment of genes associated with specific cell-types; we also restricted our analyses to specific gene ontology groups. Our analyses focused on a primary pair of single-cell expression data from the mouse visual cortex and age-related human post-mortem gene expression information from the orbitofrontal cortex. Additional pairings that used data from the hippocampus, prefrontal cortex, somatosensory cortex and blood were used to validate and test specificity of our findings. We found robust age-related up-regulation of genes that are highly expressed in oligodendrocytes and astrocytes, while genes highly expressed in layer 2/3 glutamatergic neurons were down-regulated across age. Genes not specific to any neural cell type were also down-regulated, possibly due to the bulk tissue source of the age-related genes. A gene ontology-driven dissection of the cell-type enriched genes highlighted the strong down-regulation of genes involved in synaptic transmission and cell-cell signaling in the Somatostatin (Sst neuron subtype that expresses the cyclin dependent kinase 6 (Cdk6 and in the vasoactive intestinal peptide (Vip neuron subtype expressing myosin binding protein C, slow type (Mybpc1. These findings provide new insights into cell specific susceptibility to normal aging

Atypical epidemiology of CTX-M-15 among Enterobacteriaceae from a high diversity of non-clinical niches in Angola.

Science.gov (United States)

Ribeiro, T G; Novais, Â; Peixe, L; Machado, E

2016-05-01

The objective of this study was to investigate the distribution and molecular epidemiology of ESBLs, acquired AmpCs and carbapenemases in Enterobacteriaceae from non-clinical niches in Angola, an under-researched sub-Saharan country. Eighty-one samples were recovered from healthy persons (n = 18), healthy animals (n = 33) and their environments (n = 10) or aquatic settings (n = 20) in south Angola (2013). Samples were plated onto CHROMagar™ Orientation with/without antibiotics. Standard methods were used for bacterial identification, characterization of bla genes, antibiotic susceptibility testing and conjugation assays. Clonal analysis (XbaI-PFGE, MLST and Escherichia coli phylogroups), location of bla and plasmid characterization (S1-PFGE, I-CeuI-PFGE, replicon typing and hybridization) were also performed. ESBLs (almost exclusively CTX-M-15, 98%) were detected in 21% (45/216) of the isolates, recovered from diverse non-clinical niches and belonging to different Enterobacteriaceae species (mainly E. coli). Acquired AmpCs or carbapenemases were not found. The pandemic B2-ST131 E. coli clone was not identified, but some widespread clonal complexes (CCs) from A (CC10 and CC168), B1 (CC156) or D (CC38) phylogroups were detected. blaCTX-M-15 was variably identified on typeable (29%; 100-335 kb; IncFII, IncFIIK6, IncHI2 and IncY) or non-typeable (16%; 70-330 kb) plasmids or on the chromosome (14%), while for 41% of the isolates its specific location was not determined. This study reports, for the first time in Angola, an unexpected high occurrence of CTX-M-15 in diverse non-clinical niches and Enterobacteriaceae species, and uncovers novel plasmid replicons in under-researched geographical regions. The diffusion of blaCTX-M-15 through such a high diversity of genetic backgrounds (clones, typeable/non-typeable plasmids and genetic environments) unveils an extraordinary ability for blaCTX-M-15 acquisition and mobilization favoured by unrecognized

Adaptations to endosymbiosis in a cnidarian-dinoflagellate association: differential gene expression and specific gene duplications.

Science.gov (United States)

Ganot, Philippe; Moya, Aurélie; Magnone, Virginie; Allemand, Denis; Furla, Paola; Sabourault, Cécile

2011-07-01

Trophic endosymbiosis between anthozoans and photosynthetic dinoflagellates forms the key foundation of reef ecosystems. Dysfunction and collapse of symbiosis lead to bleaching (symbiont expulsion), which is responsible for the severe worldwide decline of coral reefs. Molecular signals are central to the stability of this partnership and are therefore closely related to coral health. To decipher inter-partner signaling, we developed genomic resources (cDNA library and microarrays) from the symbiotic sea anemone Anemonia viridis. Here we describe differential expression between symbiotic (also called zooxanthellate anemones) or aposymbiotic (also called bleached) A. viridis specimens, using microarray hybridizations and qPCR experiments. We mapped, for the first time, transcript abundance separately in the epidermal cell layer and the gastrodermal cells that host photosynthetic symbionts. Transcriptomic profiles showed large inter-individual variability, indicating that aposymbiosis could be induced by different pathways. We defined a restricted subset of 39 common genes that are characteristic of the symbiotic or aposymbiotic states. We demonstrated that transcription of many genes belonging to this set is specifically enhanced in the symbiotic cells (gastroderm). A model is proposed where the aposymbiotic and therefore heterotrophic state triggers vesicular trafficking, whereas the symbiotic and therefore autotrophic state favors metabolic exchanges between host and symbiont. Several genetic pathways were investigated in more detail: i) a key vitamin K-dependant process involved in the dinoflagellate-cnidarian recognition; ii) two cnidarian tissue-specific carbonic anhydrases involved in the carbon transfer from the environment to the intracellular symbionts; iii) host collagen synthesis, mostly supported by the symbiotic tissue. Further, we identified specific gene duplications and showed that the cnidarian-specific isoform was also up-regulated both in the

Adaptations to endosymbiosis in a cnidarian-dinoflagellate association: differential gene expression and specific gene duplications.

Directory of Open Access Journals (Sweden)

Philippe Ganot

2011-07-01

Full Text Available Trophic endosymbiosis between anthozoans and photosynthetic dinoflagellates forms the key foundation of reef ecosystems. Dysfunction and collapse of symbiosis lead to bleaching (symbiont expulsion, which is responsible for the severe worldwide decline of coral reefs. Molecular signals are central to the stability of this partnership and are therefore closely related to coral health. To decipher inter-partner signaling, we developed genomic resources (cDNA library and microarrays from the symbiotic sea anemone Anemonia viridis. Here we describe differential expression between symbiotic (also called zooxanthellate anemones or aposymbiotic (also called bleached A. viridis specimens, using microarray hybridizations and qPCR experiments. We mapped, for the first time, transcript abundance separately in the epidermal cell layer and the gastrodermal cells that host photosynthetic symbionts. Transcriptomic profiles showed large inter-individual variability, indicating that aposymbiosis could be induced by different pathways. We defined a restricted subset of 39 common genes that are characteristic of the symbiotic or aposymbiotic states. We demonstrated that transcription of many genes belonging to this set is specifically enhanced in the symbiotic cells (gastroderm. A model is proposed where the aposymbiotic and therefore heterotrophic state triggers vesicular trafficking, whereas the symbiotic and therefore autotrophic state favors metabolic exchanges between host and symbiont. Several genetic pathways were investigated in more detail: i a key vitamin K-dependant process involved in the dinoflagellate-cnidarian recognition; ii two cnidarian tissue-specific carbonic anhydrases involved in the carbon transfer from the environment to the intracellular symbionts; iii host collagen synthesis, mostly supported by the symbiotic tissue. Further, we identified specific gene duplications and showed that the cnidarian-specific isoform was also up-regulated both

The HysNiche trial: hysteroscopic resection of uterine caesarean scar defect (niche) in patients with abnormal bleeding, a randomised controlled trial

NARCIS (Netherlands)

Vervoort, A. J. M. W.; van der Voet, L. F.; Witmer, M.; Thurkow, A. L.; Radder, C. M.; van Kesteren, P. J. M.; Quartero, H. W. P.; Kuchenbecker, W. K. H.; Bongers, M. Y.; Geomini, P. M. A. J.; de Vleeschouwer, L. H. M.; van Hooff, M. H. A.; van Vliet, H. A. A. M.; Veersema, S.; Renes, W. B.; van Meurs, H. S.; Bosmans, J.; Oude Rengerink, K.; Brölmann, H. A. M.; Mol, B. W. J.; Huirne, J. A. F.

2015-01-01

A caesarean section (CS) can cause a defect or disruption of the myometrium at the site of the uterine scar, called a niche. In recent years, an association between a niche and postmenstrual spotting after a CS has been demonstrated. Hysteroscopic resection of these niches is thought to reduce

The niche construction of cultural complexity: interactions between innovations, population size and the environment.

Science.gov (United States)

Fogarty, Laurel; Creanza, Nicole

2017-12-05

Niche construction is a process through which organisms alter their environments and, in doing so, influence or change the selective pressures to which they are subject. 'Cultural niche construction' refers specifically to the effect of cultural traits on the selective environments of other biological or cultural traits and may be especially important in human evolution. In addition, the relationship between population size and cultural accumulation has been the subject of extensive debate, in part because anthropological studies have demonstrated a significant association between population size and toolkit complexity in only a subset of studied cultures. Here, we review the role of cultural innovation in constructing human evolutionary niches and introduce a new model to describe the accumulation of human cultural traits that incorporates the effects of cultural niche construction. We consider the results of this model in light of available data on human toolkit sizes across populations to help elucidate the important differences between food-gathering societies and food-producing societies, in which niche construction may be a more potent force. These results support the idea that a population's relationship with its environment, represented here by cultural niche construction, should be considered alongside population size in studies of cultural complexity.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'. © 2017 The Author(s).

Diet and trophic niche of Lithobates catesbeianus (Amphibia: Anura

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Peterson T. Leivas

2012-10-01

Full Text Available Lithobates catesbeianus (Shaw, 1802 is an invasive anuran introduced in Brazil that is associated with the displacement and the decline of populations of native species worldwide. There is evidence that biological invasions are facilitated by certain attributes of the invading species, for instance niche breath, and that invasive species have a broader ecological niche with respect to native ones. We designed a study to ascertain the temporal, ontogenetic, and sex differences in the niche dynamics of the American bullfrog. We sampled monthly from June 2008 to May 2009 in the state of Paraná, southern Brazil. For each individual, we gathered biometric and stomach content data. We then estimated the niche breath of the juveniles and adults, and compared it between the sexes. A total of 104 females and 77 males were sampled. Lithobates catesbeianus has a generalist diet, preying upon invertebrates and vertebrates. Even though the diet of the studied population varied seasonally, it did not differ between the sexes nor did it respond to biometric variables. Niche breadth was more restricted in the winter than in the autumn. The trophic niche of juveniles and adults did not overlap much when compared with the trophic niche overlap between males and females. Adult males and females had a considerable niche overlap, but females had a broader trophic niche than males in the winter and in the spring. These niche characteristics point to an opportunistic predation strategy that may have facilitated the process of invasion and establishment of this species in the study area.

Differential distribution and abundance of diazotrophic bacterial communities across different soil niches using a gene-targeted clone library approach.

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Yousuf, Basit; Kumar, Raghawendra; Mishra, Avinash; Jha, Bhavanath

2014-11-01

Diazotrophs are key players of the globally important biogeochemical nitrogen cycle, having a significant role in maintaining ecosystem sustainability. Saline soils are pristine and unexplored habitats representing intriguing ecosystems expected to harbour potential diazotrophs capable of adapting in extreme conditions, and these implicated organisms are largely obscure. Differential occurrence of diazotrophs was studied by the nifH gene-targeted clone library approach. Four nifH gene clone libraries were constructed from different soil niches, that is saline soils (low and high salinity; EC 3.8 and 7.1 ds m(-1) ), and agricultural and rhizosphere soil. Additionally, the abundance of diazotrophic community members was assessed using quantitative PCR. Results showed environment-dependent metabolic versatility and the presence of nitrogen-fixing bacteria affiliated with a range of taxa, encompassing members of the Alphaproteobacteria, Betaproteobacteria, Deltaproteobacteria, Gammaproteobacteria, Cyanobacteria and Firmicutes. The analyses unveiled the dominance of Alphaproteobacteria and Gammaproteobacteria (Pseudomonas, Halorhodospira, Ectothiorhodospira, Bradyrhizobium, Agrobacterium, Amorphomonas) as nitrogen fixers in coastal-saline soil ecosystems, and Alphaproteobacteria and Betaproteobacteria (Bradyrhizobium, Azohydromonas, Azospirillum, Ideonella) in agricultural/rhizosphere ecosystems. The results revealed a repertoire of novel nitrogen-fixing bacterial guilds particularly in saline soil ecosystems. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Identification of hepatic niche harboring human acute lymphoblastic leukemic cells via the SDF-1/CXCR4 axis.

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Itaru Kato

Full Text Available In acute lymphoblastic leukemia (ALL patients, the bone marrow niche is widely known to be an important element of treatment response and relapse. Furthermore, a characteristic liver pathology observed in ALL patients implies that the hepatic microenvironment provides an extramedullary niche for leukemic cells. However, it remains unclear whether the liver actually provides a specific niche. The mechanism underlying this pathology is also poorly understood. Here, to answer these questions, we reconstituted the histopathology of leukemic liver by using patients-derived primary ALL cells into NOD/SCID/Yc (null mice. The liver pathology in this model was similar to that observed in the patients. By using this model, we clearly demonstrated that bile duct epithelial cells form a hepatic niche that supports infiltration and proliferation of ALL cells in the liver. Furthermore, we showed that functions of the niche are maintained by the SDF-1/CXCR4 axis, proposing a novel therapeutic approach targeting the extramedullary niche by inhibition of the SDF-1/CXCR4 axis. In conclusion, we demonstrated that the liver dissemination of leukemia is not due to nonselective infiltration, but rather systematic invasion and proliferation of leukemic cells in hepatic niche. Although the contribution of SDF-1/CXCR4 axis is reported in some cancer cells or leukemic niches such as bone marrow, we demonstrated that this axis works even in the extramedullary niche of leukemic cells. Our findings form the basis for therapeutic approaches that target the extramedullary niche by inhibiting the SDF-1/CXCR4 axis.

Realized niches explain spatial gradients in seasonal abundance of phytoplankton groups in the South China Sea

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Xiao, Wupeng; Wang, Lei; Laws, Edward; Xie, Yuyuan; Chen, Jixin; Liu, Xin; Chen, Bingzhang; Huang, Bangqin

2018-03-01

A basic albeit elusive goal of ocean science is to predict the structure of biological communities from the multitude of environmental conditions they experience. Estimates of the realized niche-based traits (realized traits) of phytoplankton species or functional groups in temperate seas have shown that response traits can help reveal the mechanisms responsible for structuring phytoplankton communities, but such approaches have not been tested in tropical and subtropical marginal seas. Here, we used decadal-scale studies of pigment-based phytoplankton groups and environmental conditions in the South China Sea to test whether realized traits could explain the biogeographic patterns of phytoplankton variability. We estimated the mean and breadth of the phytoplankton realized niches based on responses of the group-specific phytoplankton composition to key environmental factors, and we showed that variations of major phytoplankton groups in this system can be explained by different adaptive trade-offs to constraints imposed by temperature, irradiance, and nutrient concentrations. Differences in the patterns of trade-offs clearly separated the dominant groups from one another and generated four sets of realized traits that mirrored the observed biogeographic distribution patterns. The phytoplankton realized niches and their associated traits that we characterized in the present study could help to predict responses of phytoplankton to changes in environmental conditions in the South China Sea and could be incorporated into global biogeochemical models to anticipate shifts in community structure under future climate scenarios.

Knowledge Enrichment Analysis for Human Tissue- Specific Genes Uncover New Biological Insights

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Gong Xiu-Jun

2012-06-01

Full Text Available The expression and regulation of genes in different tissues are fundamental questions to be answered in biology. Knowledge enrichment analysis for tissue specific (TS and housekeeping (HK genes may help identify their roles in biological process or diseases and gain new biological insights.In this paper, we performed the knowledge enrichment analysis for 17,343 genes in 84 human tissues using Gene Set Enrichment Analysis (GSEA and Hypergeometric Analysis (HA against three biological ontologies: Gene Ontology (GO, KEGG pathways and Disease Ontology (DO respectively.The analyses results demonstrated that the functions of most gene groups are consistent with their tissue origins. Meanwhile three interesting new associations for HK genes and the skeletal muscle tissuegenes are found. Firstly, Hypergeometric analysis against KEGG database for HK genes disclosed that three disease terms (Parkinson’s disease, Huntington’s disease, Alzheimer’s disease are intensively enriched.Secondly, Hypergeometric analysis against the KEGG database for Skeletal Muscle tissue genes shows that two cardiac diseases of “Hypertrophic cardiomyopathy (HCM” and “Arrhythmogenic right ventricular cardiomyopathy (ARVC” are heavily enriched, which are also considered as no relationship with skeletal functions.Thirdly, “Prostate cancer” is intensively enriched in Hypergeometric analysis against the disease ontology (DO for the Skeletal Muscle tissue genes, which is a much unexpected phenomenon.

Ecological and evolutionary consequences of niche construction for its agent.

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Kylafis, Grigoris; Loreau, Michel

2008-10-01

Niche construction can generate ecological and evolutionary feedbacks that have been underinvestigated so far. We present an eco-evolutionary model that incorporates the process of niche construction to reveal its effects on the ecology and evolution of the niche-constructing agent. We consider a simple plant-soil nutrient ecosystem in which plants have the ability to increase the input of inorganic nutrient as an example of positive niche construction. On an ecological time scale, the model shows that niche construction allows the persistence of plants under infertile soil conditions that would otherwise lead to their extinction. This expansion of plants' niche, however, requires a high enough rate of niche construction and a high enough initial plant biomass to fuel the positive ecological feedback between plants and their soil environment. On an evolutionary time scale, we consider that the rates of niche construction and nutrient uptake coevolve in plants while a trade-off constrains their values. Different evolutionary outcomes are possible depending on the shape of the trade-off. We show that niche construction results in an evolutionary feedback between plants and their soil environment such that plants partially regulate soil nutrient content. The direct benefit accruing to plants, however, plays a crucial role in the evolutionary advantage of niche construction.

Stereotypical architecture of the stem cell niche is spatiotemporally established by miR-125-dependent coordination of Notch and steroid signaling.

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Yatsenko, Andriy S; Shcherbata, Halyna R

2018-02-08

Stem cell niches act as signaling platforms that regulate stem cell self-renewal and sustain stem cells throughout life; however, the specific developmental events controlling their assembly are not well understood. Here, we show that during Drosophila ovarian germline stem cell niche formation, the status of Notch signaling in the cell can be reprogrammed. This is controlled via steroid-induced miR-125 , which targets a negative regulator of Notch signaling, Tom. Thus, miR-125 acts as a spatiotemporal coordinator between paracrine Notch and endocrine steroid signaling. Moreover, a dual security mechanism for Notch signaling activation exists to ensure the robustness of niche assembly. Particularly, stem cell niche cells can be specified either via lateral inhibition, in which a niche cell precursor acquires Notch signal-sending status randomly, or via peripheral induction, whereby Delta is produced by a specific cell. When one mechanism is perturbed due to mutations, developmental defects or environmental stress, the remaining mechanism ensures that the niche is formed, perhaps abnormally, but still functional. This guarantees that the germline stem cells will have their residence, thereby securing progressive oogenesis and, thus, organism reproduction. © 2018. Published by The Company of Biologists Ltd.

Primer and interviews: The dynamic stem cell niche.

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Kiefer, Julie C

2011-03-01

A stem cell niche is a microenvironment that supports self-renewal of a population of stem cells, and their production of differentiated cells. While the definition evokes images of a stem cell Shangri-La-where a serene stem cell pool nestles within a niche that shelters and sustains it-the reality is much more tumultuous. Niches are subject to an ever-changing maelstrom of environmental factors, the ravages of old age, and the sly tactics of disease. Presented here is a basic overview of the different ways in which stem cell niches respond to local and systemic environments, and their impact on stem cell behavior. The primer culminates with a discussion of the topic with stem cell and niche biologists D. Leanne Jones, Ph.D., and Tudorita Tumbar, Ph.D. Copyright © 2011 Wiley-Liss, Inc.

Integrating genome-wide association study and expression quantitative trait loci data identifies multiple genes and gene set associated with neuroticism.

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Fan, Qianrui; Wang, Wenyu; Hao, Jingcan; He, Awen; Wen, Yan; Guo, Xiong; Wu, Cuiyan; Ning, Yujie; Wang, Xi; Wang, Sen; Zhang, Feng

2017-08-01

Neuroticism is a fundamental personality trait with significant genetic determinant. To identify novel susceptibility genes for neuroticism, we conducted an integrative analysis of genomic and transcriptomic data of genome wide association study (GWAS) and expression quantitative trait locus (eQTL) study. GWAS summary data was driven from published studies of neuroticism, totally involving 170,906 subjects. eQTL dataset containing 927,753 eQTLs were obtained from an eQTL meta-analysis of 5311 samples. Integrative analysis of GWAS and eQTL data was conducted by summary data-based Mendelian randomization (SMR) analysis software. To identify neuroticism associated gene sets, the SMR analysis results were further subjected to gene set enrichment analysis (GSEA). The gene set annotation dataset (containing 13,311 annotated gene sets) of GSEA Molecular Signatures Database was used. SMR single gene analysis identified 6 significant genes for neuroticism, including MSRA (p value=2.27×10 -10 ), MGC57346 (p value=6.92×10 -7 ), BLK (p value=1.01×10 -6 ), XKR6 (p value=1.11×10 -6 ), C17ORF69 (p value=1.12×10 -6 ) and KIAA1267 (p value=4.00×10 -6 ). Gene set enrichment analysis observed significant association for Chr8p23 gene set (false discovery rate=0.033). Our results provide novel clues for the genetic mechanism studies of neuroticism. Copyright © 2017. Published by Elsevier Inc.

Algebraic Specifications, Higher-order Types and Set-theoretic Models

DEFF Research Database (Denmark)

Kirchner, Hélène; Mosses, Peter David

2001-01-01

, and power-sets. This paper presents a simple framework for algebraic specifications with higher-order types and set-theoretic models. It may be regarded as the basis for a Horn-clause approximation to the Z framework, and has the advantage of being amenable to prototyping and automated reasoning. Standard......In most algebraic  specification frameworks, the type system is restricted to sorts, subsorts, and first-order function types. This is in marked contrast to the so-called model-oriented frameworks, which provide higer-order types, interpreted set-theoretically as Cartesian products, function spaces...... set-theoretic models are considered, and conditions are given for the existence of initial reduct's of such models. Algebraic specifications for various set-theoretic concepts are considered....

Climatic niche evolution is faster in sympatric than allopatric lineages of the butterfly genus Pyrgus.

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Pitteloud, Camille; Arrigo, Nils; Suchan, Tomasz; Mastretta-Yanes, Alicia; Vila, Roger; Dincă, Vlad; Hernández-Roldán, Juan; Brockmann, Ernst; Chittaro, Yannick; Kleckova, Irena; Fumagalli, Luca; Buerki, Sven; Pellissier, Loïc; Alvarez, Nadir

2017-04-12

Understanding how speciation relates to ecological divergence has long fascinated biologists. It is assumed that ecological divergence is essential to sympatric speciation, as a mechanism to avoid competition and eventually lead to reproductive isolation, while divergence in allopatry is not necessarily associated with niche differentiation. The impact of the spatial context of divergence on the evolutionary rates of abiotic dimensions of the ecological niche has rarely been explored for an entire clade. Here, we compare the magnitude of climatic niche shifts between sympatric versus allopatric divergence of lineages in butterflies. By combining next-generation sequencing, parametric biogeography and ecological niche analyses applied to a genus-wide phylogeny of Palaearctic Pyrgus butterflies, we compare evolutionary rates along eight climatic dimensions across sister lineages that diverged in large-scale sympatry versus allopatry. In order to examine the possible effects of the spatial scale at which sympatry is defined, we considered three sets of biogeographic assignments, ranging from narrow to broad definition. Our findings suggest higher rates of niche evolution along all climatic dimensions for sister lineages that diverge in sympatry, when using a narrow delineation of biogeographic areas. This result contrasts with significantly lower rates of climatic niche evolution found in cases of allopatric speciation, despite the biogeographic regions defined here being characterized by significantly different climates. Higher rates in allopatry are retrieved when biogeographic areas are too widely defined-in such a case allopatric events may be recorded as sympatric. Our results reveal the macro-evolutionary significance of abiotic niche differentiation involved in speciation processes within biogeographic regions, and illustrate the importance of the spatial scale chosen to define areas when applying parametric biogeographic analyses. © 2017 The Author(s).

Gene-specific correlation of RNA and protein levels in human cells and tissues

DEFF Research Database (Denmark)

Edfors, Fredrik; Danielsson, Frida; Hallström, Björn M.

2016-01-01

An important issue for molecular biology is to establish whether transcript levels of a given gene can be used as proxies for the corresponding protein levels. Here, we have developed a targeted proteomics approach for a set of human non-secreted proteins based on parallel reaction monitoring...... to measure, at steady-state conditions, absolute protein copy numbers across human tissues and cell lines and compared these levels with the corresponding mRNA levels using transcriptomics. The study shows that the transcript and protein levels do not correlate well unless a gene-specific RNA-to-protein (RTP...

The inverse niche model for food webs with parasites

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Warren, Christopher P.; Pascual, Mercedes; Lafferty, Kevin D.; Kuris, Armand M.

2010-01-01

Although parasites represent an important component of ecosystems, few field and theoretical studies have addressed the structure of parasites in food webs. We evaluate the structure of parasitic links in an extensive salt marsh food web, with a new model distinguishing parasitic links from non-parasitic links among free-living species. The proposed model is an extension of the niche model for food web structure, motivated by the potential role of size (and related metabolic rates) in structuring food webs. The proposed extension captures several properties observed in the data, including patterns of clustering and nestedness, better than does a random model. By relaxing specific assumptions, we demonstrate that two essential elements of the proposed model are the similarity of a parasite's hosts and the increasing degree of parasite specialization, along a one-dimensional niche axis. Thus, inverting one of the basic rules of the original model, the one determining consumers' generality appears critical. Our results support the role of size as one of the organizing principles underlying niche space and food web topology. They also strengthen the evidence for the non-random structure of parasitic links in food webs and open the door to addressing questions concerning the consequences and origins of this structure.

Genome-Wide Gene Set Analysis for Identification of Pathways Associated with Alcohol Dependence

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Biernacka, Joanna M.; Geske, Jennifer; Jenkins, Gregory D.; Colby, Colin; Rider, David N.; Karpyak, Victor M.; Choi, Doo-Sup; Fridley, Brooke L.

2013-01-01

It is believed that multiple genetic variants with small individual effects contribute to the risk of alcohol dependence. Such polygenic effects are difficult to detect in genome-wide association studies that test for association of the phenotype with each single nucleotide polymorphism (SNP) individually. To overcome this challenge, gene set analysis (GSA) methods that jointly test for the effects of pre-defined groups of genes have been proposed. Rather than testing for association between the phenotype and individual SNPs, these analyses evaluate the global evidence of association with a set of related genes enabling the identification of cellular or molecular pathways or biological processes that play a role in development of the disease. It is hoped that by aggregating the evidence of association for all available SNPs in a group of related genes, these approaches will have enhanced power to detect genetic associations with complex traits. We performed GSA using data from a genome-wide study of 1165 alcohol dependent cases and 1379 controls from the Study of Addiction: Genetics and Environment (SAGE), for all 200 pathways listed in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results demonstrated a potential role of the “Synthesis and Degradation of Ketone Bodies” pathway. Our results also support the potential involvement of the “Neuroactive Ligand Receptor Interaction” pathway, which has previously been implicated in addictive disorders. These findings demonstrate the utility of GSA in the study of complex disease, and suggest specific directions for further research into the genetic architecture of alcohol dependence. PMID:22717047

Hepatocyte specific expression of human cloned genes

Energy Technology Data Exchange (ETDEWEB)

Cortese, R

1986-01-01

A large number of proteins are specifically synthesized in the hepatocyte. Only the adult liver expresses the complete repertoire of functions which are required at various stages during development. There is therefore a complex series of regulatory mechanisms responsible for the maintenance of the differentiated state and for the developmental and physiological variations in the pattern of gene expression. Human hepatoma cell lines HepG2 and Hep3B display a pattern of gene expression similar to adult and fetal liver, respectively; in contrast, cultured fibroblasts or HeLa cells do not express most of the liver specific genes. They have used these cell lines for transfection experiments with cloned human liver specific genes. DNA segments coding for alpha1-antitrypsin and retinol binding protein (two proteins synthesized both in fetal and adult liver) are expressed in the hepatoma cell lines HepG2 and Hep3B, but not in HeLa cells or fibroblasts. A DNA segment coding for haptoglobin (a protein synthesized only after birth) is only expressed in the hepatoma cell line HepG2 but not in Hep3B nor in non hepatic cell lines. The information for tissue specific expression is located in the 5' flanking region of all three genes. In vivo competition experiments show that these DNA segments bind to a common, apparently limiting, transacting factor. Conventional techniques (Bal deletions, site directed mutagenesis, etc.) have been used to precisely identify the DNA sequences responsible for these effects. The emerging picture is complex: they have identified multiple, separate transcriptional signals, essential for maximal promoter activation and tissue specific expression. Some of these signals show a negative effect on transcription in fibroblast cell lines.

Topological and organizational properties of the products of house-keeping and tissue-specific genes in protein-protein interaction networks.

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Lin, Wen-Hsien; Liu, Wei-Chung; Hwang, Ming-Jing

2009-03-11

Human cells of various tissue types differ greatly in morphology despite having the same set of genetic information. Some genes are expressed in all cell types to perform house-keeping functions, while some are selectively expressed to perform tissue-specific functions. In this study, we wished to elucidate how proteins encoded by human house-keeping genes and tissue-specific genes are organized in human protein-protein interaction networks. We constructed protein-protein interaction networks for different tissue types using two gene expression datasets and one protein-protein interaction database. We then calculated three network indices of topological importance, the degree, closeness, and betweenness centralities, to measure the network position of proteins encoded by house-keeping and tissue-specific genes, and quantified their local connectivity structure. Compared to a random selection of proteins, house-keeping gene-encoded proteins tended to have a greater number of directly interacting neighbors and occupy network positions in several shortest paths of interaction between protein pairs, whereas tissue-specific gene-encoded proteins did not. In addition, house-keeping gene-encoded proteins tended to connect with other house-keeping gene-encoded proteins in all tissue types, whereas tissue-specific gene-encoded proteins also tended to connect with other tissue-specific gene-encoded proteins, but only in approximately half of the tissue types examined. Our analysis showed that house-keeping gene-encoded proteins tend to occupy important network positions, while those encoded by tissue-specific genes do not. The biological implications of our findings were discussed and we proposed a hypothesis regarding how cells organize their protein tools in protein-protein interaction networks. Our results led us to speculate that house-keeping gene-encoded proteins might form a core in human protein-protein interaction networks, while clusters of tissue-specific gene

Maternal diets trigger sex-specific divergent trajectories of gene expression and epigenetic systems in mouse placenta.

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Anne Gabory

Full Text Available Males and females responses to gestational overnutrition set the stage for subsequent sex-specific differences in adult onset non communicable diseases. Placenta, as a widely recognized programming agent, contibutes to the underlying processes. According to our previous findings, a high-fat diet during gestation triggers sex-specific epigenetic alterations within CpG and throughout the genome, together with the deregulation of clusters of imprinted genes. We further investigated the impact of diet and sex on placental histology, transcriptomic and epigenetic signatures in mice. Both basal gene expression and response to maternal high-fat diet were sexually dimorphic in whole placentas. Numerous genes showed sexually dimorphic expression, but only 11 genes regardless of the diet. In line with the key role of genes belonging to the sex chromosomes, 3 of these genes were Y-specific and 3 were X-specific. Amongst all the genes that were differentially expressed under a high-fat diet, only 16 genes were consistently affected in both males and females. The differences were not only quantitative but remarkably qualitative. The biological functions and networks of genes dysregulated differed markedly between the sexes. Seven genes of the epigenetic machinery were dysregulated, due to effects of diet, sex or both, including the Y- and X-linked histone demethylase paralogues Kdm5c and Kdm5d, which could mark differently male and female epigenomes. The DNA methyltransferase cofactor Dnmt3l gene expression was affected, reminiscent of our previous observation of changes in global DNA methylation. Overall, this striking sexual dimorphism of programming trajectories impose a considerable revision of the current dietary interventions protocols.

Transcriptomic insights into the alternative splicing-mediated adaptation of the entomopathogenic fungus Beauveria bassiana to host niches: autophagy-related gene 8 as an example.

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Dong, Wei-Xia; Ding, Jin-Li; Gao, Yang; Peng, Yue-Jin; Feng, Ming-Guang; Ying, Sheng-Hua

2017-10-01

Alternative splicing (AS) regulates various biological processes in fungi by extending the cellular proteome. However, comprehensive studies investigating AS in entomopathogenic fungi are lacking. Based on transcriptome data obtained via dual RNA-seq, the first overview of AS events was developed for Beauveria bassiana growing in an insect haemocoel. The AS was demonstrated for 556 of 8840 expressed genes, accounting for 5.4% of the total genes in B. bassiana. Intron retention was the most abundant type of AS, accounting for 87.1% of all splicing events and exon skipping events were rare, only accounting for 2.0% of all events. Functional distribution analysis indicated an association between alternatively spliced genes and several physiological processes. Notably, B. bassiana autophagy-related gene 8 (BbATG8), an indispensable gene for autophagy, was spliced at an alternative 5' splice site to generate two transcripts (BbATG8-α and BbATG8-β). The BbATG8-α transcript was necessary for fungal autophagy and oxidation tolerance, while the BbATG8-β transcript was not. These two transcripts differentially contributed to the formation of conidia or blastospores as well as fungal virulence. Thus, AS acts as a powerful post-transcriptional regulatory strategy in insect mycopathogens and significantly mediates fungal transcriptional adaption to host niches. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Astrocitary niches in human adult medulla oblongata.

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Rusu, Mugurel Constantin; Dermengiu, Dan; Loreto, Carla; Motoc, Andrei Gheorghe Marius; Pop, Elena

2013-04-01

Astrocytes are considered as neuromodulators of the CNS. Whereas experimental studies on astrocitary functions are gaining importance, the anatomy of the astrocitary niches in the human CNS has been overlooked. The study was performed on the brainstem of 10 adult cadavers. We aimed to determine astrocitary niches in the human medulla oblongata using immunohistochemical labeling with vimentin and also CD34 immunostaining to accurately diagnose associated microvessels. Niches rich in astrocytes were identified as follows: (a) the superficial layer of astrocytes, ventral and ventrolateral, in the rostral medulla oblongata; (b) the median raphe; (c) medullary nuclei: arcuate nucleus, area postrema, nucleus of the solitary tract; (d) the subependymal zone (SEZ, caudal medulla) and subventricular zone (SVZ, rostral medulla). Astrocytes were scarce in the ventrolateral medulla, and mostly present within the pyramidal tract and the olivary nucleus. Apart from the SEZ and SVZ, the brainstem niches of astrocytes mostly overlap those regions known to perform roles as central respiratory chemoreceptors. The astrocytes of the SEZ and SVZ, which are known as stem cell niches, are related to an increased microvascular density. Copyright © 2012 Elsevier GmbH. All rights reserved.

Glioblastoma niches: from the concept to the phenotypical reality.

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Schiffer, Davide; Mellai, Marta; Bovio, Enrica; Bisogno, Ilaria; Casalone, Cristina; Annovazzi, Laura

2018-05-08

Recently, the concept of niches as sites of tumor progression, invasion, and angiogenesis in glioblastoma (GB) has been extensively debated. Niches, considered the sites in which glioblastoma stem cells (GSCs) reside, have been classified as perivascular, perinecrotic, and invasive. However, from a neuropathological point of view, it is not easy to establish when a tumor structure can be considered a niche. The relevant literature has been reviewed in the light of our recent experience on the subject. As for perinecrotic niches, the occurrence of GSCs around necrosis is interpreted as triggered by hypoxia through HIF-1α. Our alternative hypothesis is that, together with progenitors, they are the cell constituents of hyper-proliferative areas of GB, where perinecrotic niches have developed, and they would, therefore, represent the remnants of GSCs/progenitors spared by the developing necrosis. Perivascular structures originate from both transport vessels and exchange vessels, i.e., venules, arterioles, or the undefinable neo-formed small vessels, but only those in which a direct contact between GSCs/progenitors and endothelial cells occurs can be called niches. Both pericytes and microglia/macrophages play a role in niche function: Macrophages of blood origin invade GB only after the appearance of "mother vessels" with consequent blood-brain barrier disruption. Not all vessel/tumor cell structures can be considered niches, that is, crucial sites of tumor progression, invasion, and angiogenesis.

Niche conservatism and the invasive potential of the wild boar.

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Sales, Lilian Patrícia; Ribeiro, Bruno R; Hayward, Matt Warrington; Paglia, Adriano; Passamani, Marcelo; Loyola, Rafael

2017-09-01

Niche conservatism, i.e. the retention of a species' fundamental niche through evolutionary time, is cornerstone for biological invasion assessments. The fact that species tend to maintain their original climate niche allows predictive maps of invasion risk to anticipate potential invadable areas. Unravelling the mechanisms driving niche shifts can shed light on the management of invasive species. Here, we assessed niche shifts in one of the world's worst invasive species: the wild boar Sus scrofa. We also predicted potential invadable areas based on an ensemble of three ecological niche modelling methods, and evaluated the performance of models calibrated with native vs. pooled (native plus invaded) species records. By disentangling the drivers of change on the exotic wild boar population's niches, we found strong evidence for niche conservatism during biological invasion. Ecological niche models calibrated with both native and pooled range records predicted convergent areas. Also, observed niche shifts are mostly explained by niche unfilling, i.e. there are unoccupied areas in the exotic range where climate is analogous to the native range. Niche unfilling is expected as result of recent colonization and ongoing dispersal, and was potentially stronger for the Neotropics, where a recent wave of introductions for pig-farming and game-hunting has led to high wild boar population growth rates. The invasive potential of wild boar in the Neotropics is probably higher than in other regions, which has profound management implications if we are to prevent their invasion into species-rich areas, such as Amazonia, coupled with expansion of African swine fever and possibly great economic losses. Although the originally Eurasian-wide distribution suggests a pre-adaptation to a wide array of climates, the wild boar world-wide invasion does not exhibit evidence of niche evolution. The invasive potential of the wild boar therefore probably lies on the reproductive, dietary and

Ecological niches of open ocean phytoplankton taxa

DEFF Research Database (Denmark)

Brun, Philipp Georg; Vogt, Meike; Payne, Mark

2015-01-01

We characterize the realized ecological niches of 133 phytoplankton taxa in the open ocean based on observations from the MAREDAT initiative and a statistical species distribution model (MaxEnt). The models find that the physical conditions (mixed layer depth, temperature, light) govern large...... conditions in the open ocean. Our estimates of the realized niches roughly match the predictions of Reynolds' C-S-R model for the global ocean, namely that taxa classified as nutrient stress tolerant have niches at lower nutrient and higher irradiance conditions than light stress tolerant taxa. Yet...

The extraocular muscle stem cell niche is resistant to ageing and disease

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Luigi eFormicola

2014-12-01

Full Text Available Specific muscles are spared in many degenerative myopathies. Most notably, the extraocular muscles (EOMs do not show clinical signs of late stage myopathies including the accumulation of fibrosis and fat. It has been proposed that an altered stem cell niche underlies the resistance of EOMs in these pathologies, however, to date, no reports have provided a detailed characterization of the EOM stem cell niche. PW1/Peg3 is expressed in progenitor cells in all adult tissues including satellite cells and a subset of interstitial non-satellite cell progenitors in muscle. These PW1-positive interstitial cells (PICs include a fibroadipogenic progenitor population (FAPs that give rise to fat and fibrosis in late stage myopathies. PICs/FAPs are mobilized following injury and FAPs exert a promyogenic role upon myoblasts in vitro but require the presence of a minimal population of satellite cells in vivo. We and others recently described that FAPs express promyogenic factors while satellite cells express antimyogenic factors suggesting that PICs/FAPs act as support niche cells in skeletal muscle through paracrine interactions. We analyzed the EOM stem cell niche in young adult and aged wild-type mice and found that the balance between PICs and satellite cells within the EOM stem cell niche is maintained throughout life. Moreover, in the adult mdx mouse model for Duchenne muscular dystrophy, the EOM stem cell niche is unperturbed compared to normal mice, in contrast to Tibialis Anterior (TA muscle, which displays signs of ongoing degeneration/regeneration. Regenerating mdx TA shows increased levels of both PICs and satellite cells, comparable to normal unaffected EOMs. We propose that the increase in PICs that we observe in normal EOMs contributes to preserving the integrity of the myofibers and satellite cells. Our data suggest that molecular cues regulating muscle regeneration are intrinsic properties of EOMs.

Exploring the potential relevance of human-specific genes to complex disease

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Cooper David N

2011-01-01

Full Text Available Abstract Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specific genes might provide new insights into the genetics of complex disease. Cross-comparison with the Human Gene Mutation Database (http://www.hgmd.org revealed a number of examples of disease-causing and disease-associated mutations in putatively human-specific genes. A sizeable proportion of these were missense polymorphisms associated with complex disease. Since both human-specific genes and genes associated with complex disease have often experienced particularly rapid rates of evolutionary change, either due to weaker purifying selection or positive selection, it is proposed that a significant number of human-specific genes may play a role in complex disease.

Foxl1-Expressing Mesenchymal Cells Constitute the Intestinal Stem Cell NicheSummary

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Reina Aoki

2016-03-01

Full Text Available Background & Aims: Intestinal epithelial stem cells that express leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5 and/or B cell specific Moloney murine leukemia virus integration site 1 (Bmi1 continuously replicate and generate differentiated cells throughout life. Previously, Paneth cells were suggested to constitute an epithelium-intrinsic niche that regulates the behavior of these stem cells. However, ablating Paneth cells has no effect on the maintenance of functional stem cells. Here, we show definitively that a small subset of mesenchymal subepithelial cells expressing the winged-helix transcription factor forkhead box l1 (Foxl1 are a critical component of the intestinal stem cell niche. Methods: We genetically ablated Foxl1+ mesenchymal cells in adult mice using 2 separate models by expressing either the human or simian diphtheria toxin receptor under Foxl1 promoter control. Conclusions: Killing Foxl1+ cells by diphtheria toxin administration led to an abrupt cessation of proliferation of both epithelial stem- and transit-amplifying progenitor cell populations that was associated with a loss of active Wnt signaling to the intestinal epithelium. Therefore, Foxl1-expressing mesenchymal cells constitute the fundamental niche for intestinal stem cells. Keywords: Intestinal Stem Cell Niche, Wnt, Mesenchyme

Tissue-specific functional networks for prioritizing phenotype and disease genes.

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Yuanfang Guan

Full Text Available Integrated analyses of functional genomics data have enormous potential for identifying phenotype-associated genes. Tissue-specificity is an important aspect of many genetic diseases, reflecting the potentially different roles of proteins and pathways in diverse cell lineages. Accounting for tissue specificity in global integration of functional genomics data is challenging, as "functionality" and "functional relationships" are often not resolved for specific tissue types. We address this challenge by generating tissue-specific functional networks, which can effectively represent the diversity of protein function for more accurate identification of phenotype-associated genes in the laboratory mouse. Specifically, we created 107 tissue-specific functional relationship networks through integration of genomic data utilizing knowledge of tissue-specific gene expression patterns. Cross-network comparison revealed significantly changed genes enriched for functions related to specific tissue development. We then utilized these tissue-specific networks to predict genes associated with different phenotypes. Our results demonstrate that prediction performance is significantly improved through using the tissue-specific networks as compared to the global functional network. We used a testis-specific functional relationship network to predict genes associated with male fertility and spermatogenesis phenotypes, and experimentally confirmed one top prediction, Mbyl1. We then focused on a less-common genetic disease, ataxia, and identified candidates uniquely predicted by the cerebellum network, which are supported by both literature and experimental evidence. Our systems-level, tissue-specific scheme advances over traditional global integration and analyses and establishes a prototype to address the tissue-specific effects of genetic perturbations, diseases and drugs.

Evidence for intron length conservation in a set of mammalian genes associated with embryonic development

LENUS (Irish Health Repository)

2011-10-05

Abstract Background We carried out an analysis of intron length conservation across a diverse group of nineteen mammalian species. Motivated by recent research suggesting a role for time delays associated with intron transcription in gene expression oscillations required for early embryonic patterning, we searched for examples of genes that showed the most extreme conservation of total intron content in mammals. Results Gene sets annotated as being involved in pattern specification in the early embryo or containing the homeobox DNA-binding domain, were significantly enriched among genes with highly conserved intron content. We used ancestral sequences reconstructed with probabilistic models that account for insertion and deletion mutations to distinguish insertion and deletion events on lineages leading to human and mouse from their last common ancestor. Using a randomization procedure, we show that genes containing the homeobox domain show less change in intron content than expected, given the number of insertion and deletion events within their introns. Conclusions Our results suggest selection for gene expression precision or the existence of additional development-associated genes for which transcriptional delay is functionally significant.

Cellular population dynamics control the robustness of the stem cell niche

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Adam L. MacLean

2015-11-01

Full Text Available Within populations of cells, fate decisions are controlled by an indeterminate combination of cell-intrinsic and cell-extrinsic factors. In the case of stem cells, the stem cell niche is believed to maintain ‘stemness’ through communication and interactions between the stem cells and one or more other cell-types that contribute to the niche conditions. To investigate the robustness of cell fate decisions in the stem cell hierarchy and the role that the niche plays, we introduce simple mathematical models of stem and progenitor cells, their progeny and their interplay in the niche. These models capture the fundamental processes of proliferation and differentiation and allow us to consider alternative possibilities regarding how niche-mediated signalling feedback regulates the niche dynamics. Generalised stability analysis of these stem cell niche systems enables us to describe the stability properties of each model. We find that although the number of feasible states depends on the model, their probabilities of stability in general do not: stem cell–niche models are stable across a wide range of parameters. We demonstrate that niche-mediated feedback increases the number of stable steady states, and show how distinct cell states have distinct branching characteristics. The ecological feedback and interactions mediated by the stem cell niche thus lend (surprisingly high levels of robustness to the stem and progenitor cell population dynamics. Furthermore, cell–cell interactions are sufficient for populations of stem cells and their progeny to achieve stability and maintain homeostasis. We show that the robustness of the niche – and hence of the stem cell pool in the niche – depends only weakly, if at all, on the complexity of the niche make-up: simple as well as complicated niche systems are capable of supporting robust and stable stem cell dynamics.

The hidden Niemann-Pick type C patient: clinical niches for a rare inherited metabolic disease.

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Hendriksz, Christian J; Anheim, Mathieu; Bauer, Peter; Bonnot, Olivier; Chakrapani, Anupam; Corvol, Jean-Christophe; de Koning, Tom J; Degtyareva, Anna; Dionisi-Vici, Carlo; Doss, Sarah; Duning, Thomas; Giunti, Paola; Iodice, Rosa; Johnston, Tracy; Kelly, Dierdre; Klünemann, Hans-Hermann; Lorenzl, Stefan; Padovani, Alessandro; Pocovi, Miguel; Synofzik, Matthis; Terblanche, Alta; Then Bergh, Florian; Topçu, Meral; Tranchant, Christine; Walterfang, Mark; Velten, Christian; Kolb, Stefan A

2017-05-01

Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups ("clinical niches") have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes. Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included. Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches. Several clinical niches have been identified that harbor patients at increased risk of NP-C.

Gene set of nuclear-encoded mitochondrial regulators is enriched for common inherited variation in obesity.

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Nadja Knoll

Full Text Available There are hints of an altered mitochondrial function in obesity. Nuclear-encoded genes are relevant for mitochondrial function (3 gene sets of known relevant pathways: (1 16 nuclear regulators of mitochondrial genes, (2 91 genes for oxidative phosphorylation and (3 966 nuclear-encoded mitochondrial genes. Gene set enrichment analysis (GSEA showed no association with type 2 diabetes mellitus in these gene sets. Here we performed a GSEA for the same gene sets for obesity. Genome wide association study (GWAS data from a case-control approach on 453 extremely obese children and adolescents and 435 lean adult controls were used for GSEA. For independent confirmation, we analyzed 705 obesity GWAS trios (extremely obese child and both biological parents and a population-based GWAS sample (KORA F4, n = 1,743. A meta-analysis was performed on all three samples. In each sample, the distribution of significance levels between the respective gene set and those of all genes was compared using the leading-edge-fraction-comparison test (cut-offs between the 50(th and 95(th percentile of the set of all gene-wise corrected p-values as implemented in the MAGENTA software. In the case-control sample, significant enrichment of associations with obesity was observed above the 50(th percentile for the set of the 16 nuclear regulators of mitochondrial genes (p(GSEA,50 = 0.0103. This finding was not confirmed in the trios (p(GSEA,50 = 0.5991, but in KORA (p(GSEA,50 = 0.0398. The meta-analysis again indicated a trend for enrichment (p(MAGENTA,50 = 0.1052, p(MAGENTA,75 = 0.0251. The GSEA revealed that weak association signals for obesity might be enriched in the gene set of 16 nuclear regulators of mitochondrial genes.

COREMIC: a web-tool to search for a niche associated CORE MICrobiome

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Richard R. Rodrigues

2018-02-01

Full Text Available Microbial diversity on earth is extraordinary, and soils alone harbor thousands of species per gram of soil. Understanding how this diversity is sorted and selected into habitat niches is a major focus of ecology and biotechnology, but remains only vaguely understood. A systems-biology approach was used to mine information from databases to show how it can be used to answer questions related to the core microbiome of habitat-microbe relationships. By making use of the burgeoning growth of information from databases, our tool “COREMIC” meets a great need in the search for understanding niche partitioning and habitat-function relationships. The work is unique, furthermore, because it provides a user-friendly statistically robust web-tool (http://coremic2.appspot.com or http://core-mic.com, developed using Google App Engine, to help in the process of database mining to identify the “core microbiome” associated with a given habitat. A case study is presented using data from 31 switchgrass rhizosphere community habitats across a diverse set of soil and sampling environments. The methodology utilizes an outgroup of 28 non-switchgrass (other grasses and forbs to identify a core switchgrass microbiome. Even across a diverse set of soils (five environments, and conservative statistical criteria (presence in more than 90% samples and FDR q-val <0.05% for Fisher’s exact test a core set of bacteria associated with switchgrass was observed. These included, among others, closely related taxa from Lysobacter spp., Mesorhizobium spp, and Chitinophagaceae. These bacteria have been shown to have functions related to the production of bacterial and fungal antibiotics and plant growth promotion. COREMIC can be used as a hypothesis generating or confirmatory tool that shows great potential for identifying taxa that may be important to the functioning of a habitat (e.g. host plant. The case study, in conclusion, shows that COREMIC can identify key habitat-specific

On-the-fly selection of cell-specific enhancers, genes, miRNAs and proteins across the human body using SlideBase

DEFF Research Database (Denmark)

Ienasescu, Hans-Ioan; Li, Kang; Andersson, Robin

2016-01-01

Genomics consortia have produced large datasets profiling the expression of genes, micro-RNAs, enhancers and more across human tissues or cells. There is a need for intuitive tools to select subsets of such data that is the most relevant for specific studies. To this end, we present Slide...... for individual cell types/tissues, producing sets of genes, enhancers etc. which satisfy these constraints. Changes in slider settings result in simultaneous changes in the selected sets, updated in real time. SlideBase is linked to major databases from genomics consortia, including FANTOM, GTEx, The Human...

Angiocrine functions of organ-specific endothelial cells

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Rafii, Shahin; Butler, Jason M; Ding, Bi-Sen

2016-01-01

Preface Endothelial cells lining blood vessel capillaries are not just passive conduits for delivering blood. Tissue-specific endothelium establish specialized vascular niches that deploy specific sets of growth factors, known as angiocrine factors, which actively participate in inducing, specifying, patterning, and guiding organ regeneration and maintaining homeostasis and metabolism. Angiocrine factors upregulated in response to injury orchestrates self-renewal and differentiation of tissue-specific repopulating resident stem and progenitor cells into functional organs. Uncovering the precise mechanisms whereby physiological-levels of angiocrine factors are spatially and temporally produced, and distributed by organotypic endothelium to repopulating cells, will lay the foundation for driving organ repair without scarring. PMID:26791722

Ten Niche Strategies To Commercialize New High-Tech Products

NARCIS (Netherlands)

Ortt, J.R.; Langley, D.J.; Pals, N.

2013-01-01

There are serious gaps in the scientific literature relating to niche strategies as a means for commercializing new high-tech products. In particular, there is no clarity about what types of niche strategies can be distinguished, or how a niche strategy can be selected to suit a certain ituation. In

Individual foraging strategies reveal niche overlap between endangered galapagos pinnipeds.

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Stella Villegas-Amtmann

Full Text Available Most competition studies between species are conducted from a population-level approach. Few studies have examined inter-specific competition in conjunction with intra-specific competition, with an individual-based approach. To our knowledge, none has been conducted on marine top predators. Sympatric Galapagos fur seals (Arctocephalus galapagoensis and sea lions (Zalophus wollebaeki share similar geographic habitats and potentially compete. We studied their foraging niche overlap at Cabo Douglas, Fernandina Island from simultaneously collected dive and movement data to examine spatial and temporal inter- and intra-specific competition. Sea lions exhibited 3 foraging strategies (shallow, intermediate and deep indicating intra-specific competition. Fur seals exhibited one foraging strategy, diving predominantly at night, between 0-80 m depth and mostly at 19-22 h. Most sea lion dives also occurred at night (63%, between 0-40 m, within fur seals' diving depth range. 34% of sea lions night dives occurred at 19-22 h, when fur seals dived the most, but most of them occurred at dawn and dusk, when fur seals exhibited the least amount of dives. Fur seals and sea lions foraging behavior overlapped at 19 and 21 h between 0-30 m depths. Sea lions from the deep diving strategy exhibited the greatest foraging overlap with fur seals, in time (19 h, depth during overlapping time (21-24 m, and foraging range (37.7%. Fur seals foraging range was larger. Cabo Douglas northwest coastal area, region of highest diving density, is a foraging "hot spot" for both species. Fur seals and sea lions foraging niche overlap occurred, but segregation also occurred; fur seals primarily dived at night, while sea lions exhibited night and day diving. Both species exploited depths and areas exclusive to their species. Niche breadth generally increases with environmental uncertainty and decreased productivity. Potential competition between these species could be greater during

Genome-scale analysis of positional clustering of mouse testis-specific genes

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Lee Bernett TK

2005-01-01

Full Text Available Abstract Background Genes are not randomly distributed on a chromosome as they were thought even after removal of tandem repeats. The positional clustering of co-expressed genes is known in prokaryotes and recently reported in several eukaryotic organisms such as Caenorhabditis elegans, Drosophila melanogaster, and Homo sapiens. In order to further investigate the mode of tissue-specific gene clustering in higher eukaryotes, we have performed a genome-scale analysis of positional clustering of the mouse testis-specific genes. Results Our computational analysis shows that a large proportion of testis-specific genes are clustered in groups of 2 to 5 genes in the mouse genome. The number of clusters is much higher than expected by chance even after removal of tandem repeats. Conclusion Our result suggests that testis-specific genes tend to cluster on the mouse chromosomes. This provides another piece of evidence for the hypothesis that clusters of tissue-specific genes do exist.

β3-Adrenergic Regulation of EPC Features Through Manipulation of the Bone Marrow MSC Niche.

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Vafaei, Rana; Nassiri, Seyed Mahdi; Siavashi, Vahid

2017-12-01

Mesenchymal stem cells (MSCs) reside in a specific niche in the bone marrow, however, biological features of this niche are still not fully understood. Given the interactions of MSCs with endothelial cells in different tissues, bone marrow MSC niche may influence the biological features of endothelial progenitor cells (EPCs). To understand the role of the sympathetic nervous system in regulation of the MSC niche, we examined whether the manipulation of the MSC niche via β3-adrenergic signals will affect EPC features. A selective β3 agonist (BRL37344) or a β3 antagonist (SR59230A) was administered in mice for 2 weeks to determine the potential effects of these regimens on the population of CD133 + stem cells in the bone marrow. Then, bone marrow-derived MSCs and EPCs were harvested and expanded from the mice to examine the effect of changes in the MSC niche on EPC features. Improved MSC colony forming potency with increased bone marrow stromal cell-derived factor 1 (SDF-1) (also known as C-X-C motif chemokine 12 [CXCL12]) expression was shown as a result of intensification of the bone marrow adrenergic signals through BRL37344 injection. On the other hand, the blockage of these signals limited the expression level of SDF-1 and resulted in bone marrow enrichment of CD133 + cells. Manipulation of the MSC niche and decreased SDF-1 expression via SR59230A injection also prompted EPCs to form more colonies with augmented proliferation and differentiation capacity. Overall, our results indicate that the β3-adrenergic signals regulate the MSC niche, thereby resulting in modulation of EPC biological features. J. Cell. Biochem. 118: 4753-4761, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Root parasitic plant Orobanche aegyptiaca and shoot parasitic plant Cuscuta australis obtained Brassicaceae-specific strictosidine synthase-like genes by horizontal gene transfer.

Science.gov (United States)

Zhang, Dale; Qi, Jinfeng; Yue, Jipei; Huang, Jinling; Sun, Ting; Li, Suoping; Wen, Jian-Fan; Hettenhausen, Christian; Wu, Jinsong; Wang, Lei; Zhuang, Huifu; Wu, Jianqiang; Sun, Guiling

2014-01-13

Besides gene duplication and de novo gene generation, horizontal gene transfer (HGT) is another important way of acquiring new genes. HGT may endow the recipients with novel phenotypic traits that are important for species evolution and adaption to new ecological niches. Parasitic systems expectedly allow the occurrence of HGT at relatively high frequencies due to their long-term physical contact. In plants, a number of HGT events have been reported between the organelles of parasites and the hosts, but HGT between host and parasite nuclear genomes has rarely been found. A thorough transcriptome screening revealed that a strictosidine synthase-like (SSL) gene in the root parasitic plant Orobanche aegyptiaca and the shoot parasitic plant Cuscuta australis showed much higher sequence similarities with those in Brassicaceae than with those in their close relatives, suggesting independent gene horizontal transfer events from Brassicaceae to these parasites. These findings were strongly supported by phylogenetic analysis and their identical unique amino acid residues and deletions. Intriguingly, the nucleus-located SSL genes in Brassicaceae belonged to a new member of SSL gene family, which were originated from gene duplication. The presence of introns indicated that the transfer occurred directly by DNA integration in both parasites. Furthermore, positive selection was detected in the foreign SSL gene in O. aegyptiaca but not in C. australis. The expression of the foreign SSL genes in these two parasitic plants was detected in multiple development stages and tissues, and the foreign SSL gene was induced after wounding treatment in C. australis stems. These data imply that the foreign genes may still retain certain functions in the recipient species. Our study strongly supports that parasitic plants can gain novel nuclear genes from distantly related host species by HGT and the foreign genes may execute certain functions in the new hosts.

Niche conservatism in Gynandropaa frogs on the southeastern Qinghai-Tibetan Plateau.

Science.gov (United States)

Hu, Junhua; Broennimann, Olivier; Guisan, Antoine; Wang, Bin; Huang, Yan; Jiang, Jianping

2016-09-07

The role of ecological niche in lineage diversification has been the subject of long-standing interest of ecologists and evolutionary biologists. Gynandropaa frogs diversified into three independent clades endemic to the southeastern Qinghai-Tibetan Plateau. Here, we address the question whether these clades kept the same niche after separation, and what it tells us about possible diversification processes. We applied predictions in geographical (G)-space and tests of niche conservatism in environmental (E)-space. Niche models in G-space indicate separate regions with high suitability for the different clades, with some potential areas of sympatry. While the pair of central and eastern clades displayed the largest niche overlap for most variables, and strict niche equivalency was rejected for all clade-pairs, we found no strong evidence for niche divergence, but rather the signature of niche conservatism compared to null models in E-space. These results suggest a common ancestral ecological niche, and as such give good support to divergence through allopatric speciation, but alternative explanations are also possible. Our findings illustrate how testing for niche conservatism in lineage diversification can provide insights into underlying speciation processes, and how this information may guide further research and conservation practices, as illustrated here for amphibians on the Qinghai-Tibetan Plateau.

Unveiling current Guanaco distribution in chile based upon niche structure of phylogeographic lineages: Andean puna to subpolar forests.

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Benito A González

Full Text Available Niche description and differentiation at broad geographic scales have been recent major topics in ecology and evolution. Describing the environmental niche structure of sister taxa with known evolutionary trajectories stands out as a useful exercise in understanding niche requirements. Here we model the environmental niche structure and distribution of the recently resolved phylogeography of guanaco (Lama guanicoe lineages on the western slope of the southern Andes. Using a maximum entropy framework, field data, and information on climate, topography, human density, and vegetation cover, we identify differences between the two subspecies (L.g.cacsilensis, L.g.guanicoe and their intermediate-hybrid lineage, that most likely determine the distribution of this species. While aridity seems to be a major factor influencing the distribution at the species-level (annual precipitation <900 mm, we also document important differences in niche specificity for each subspecies, where distribution of Northern lineage is explained mainly by elevation (mean = 3,413 m and precipitation seasonality (mean = 161 mm, hybrid lineage by annual precipitation (mean = 139 mm, and Southern subspecies by annual precipitation (mean = 553 mm, precipitation seasonality (mean = 21 mm and grass cover (mean = 8.2%. Among lineages, we detected low levels of niche overlap: I (Similarity Index = 0.06 and D (Schoener's Similarity Index = 0.01; and higher levels when comparing Northern and Southern subspecies with hybrids lineage ( I = 0.32-0.10 and D = 0.12-0.03, respectively. This suggests that important ecological and/or evolutionary processes are shaping the niche of guanacos in Chile, producing discrepancies when comparing range distribution at the species-level (81,756 km(2 with lineages-level (65,321 km(2. The subspecies-specific description of niche structure is provided here based upon detailed spatial distribution of the lineages of guanacos in Chile. Such description

Mechanism-based biomarker gene sets for glutathione depletion-related hepatotoxicity in rats

International Nuclear Information System (INIS)

Gao Weihua; Mizukawa, Yumiko; Nakatsu, Noriyuki; Minowa, Yosuke; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro

2010-01-01

Chemical-induced glutathione depletion is thought to be caused by two types of toxicological mechanisms: PHO-type glutathione depletion [glutathione conjugated with chemicals such as phorone (PHO) or diethyl maleate (DEM)], and BSO-type glutathione depletion [i.e., glutathione synthesis inhibited by chemicals such as L-buthionine-sulfoximine (BSO)]. In order to identify mechanism-based biomarker gene sets for glutathione depletion in rat liver, male SD rats were treated with various chemicals including PHO (40, 120 and 400 mg/kg), DEM (80, 240 and 800 mg/kg), BSO (150, 450 and 1500 mg/kg), and bromobenzene (BBZ, 10, 100 and 300 mg/kg). Liver samples were taken 3, 6, 9 and 24 h after administration and examined for hepatic glutathione content, physiological and pathological changes, and gene expression changes using Affymetrix GeneChip Arrays. To identify differentially expressed probe sets in response to glutathione depletion, we focused on the following two courses of events for the two types of mechanisms of glutathione depletion: a) gene expression changes occurring simultaneously in response to glutathione depletion, and b) gene expression changes after glutathione was depleted. The gene expression profiles of the identified probe sets for the two types of glutathione depletion differed markedly at times during and after glutathione depletion, whereas Srxn1 was markedly increased for both types as glutathione was depleted, suggesting that Srxn1 is a key molecule in oxidative stress related to glutathione. The extracted probe sets were refined and verified using various compounds including 13 additional positive or negative compounds, and they established two useful marker sets. One contained three probe sets (Akr7a3, Trib3 and Gstp1) that could detect conjugation-type glutathione depletors any time within 24 h after dosing, and the other contained 14 probe sets that could detect glutathione depletors by any mechanism. These two sets, with appropriate scoring

Kidney-specific Sonoporation-mediated Gene Transfer.

Science.gov (United States)

Ishida, Ryo; Kami, Daisuke; Kusaba, Tetsuro; Kirita, Yuhei; Kishida, Tsunao; Mazda, Osam; Adachi, Takaomi; Gojo, Satoshi

2016-02-01

Sonoporation can deliver agents to target local organs by systemic administration, while decreasing the associated risk of adverse effects. Sonoporation has been used for a variety of materials and in a variety of organs. Herein, we demonstrated that local sonoporation to the kidney can offer highly efficient transfer of oligonucleotides, which were systemically administrated to the tubular epithelium with high specificity. Ultrasonic wave irradiation to the kidney collapsed the microbubbles and transiently affected the glomerular filtration barrier and increased glomerular permeability. Oligonucleotides were passed through the barrier all at once and were absorbed throughout the tubular epithelium. Tumor necrosis factor alpha (TNFα), which plays a central role in renal ischemia-reperfusion injury, was targeted using small interfering RNA (siRNA) with renal sonoporation in a murine model. The reduction of TNFα expression after single gene transfer significantly inhibited the expression of kidney injury markers, suggesting that systemic administration of siRNA under temporary and local sonoporation could be applicable in the clinical setting of ischemic acute kidney injury.

Phylogenetic niche conservatism explains an inverse latitudinal diversity gradient in freshwater arthropods

Science.gov (United States)

Morinière, Jérôme; van Dam, Matthew H.; Hawlitschek, Oliver; Bergsten, Johannes; Michat, Mariano C.; Hendrich, Lars; Ribera, Ignacio; Toussaint, Emmanuel F. A.; Balke, Michael

2016-05-01

The underlying mechanisms responsible for the general increase in species richness from temperate regions to the tropics remain equivocal. Many hypotheses have been proposed to explain this astonishing pattern but additional empirical studies are needed to shed light on the drivers at work. Here we reconstruct the evolutionary history of the cosmopolitan diving beetle subfamily Colymbetinae, the majority of which are found in the Northern hemisphere, hence exhibiting an inversed latitudinal diversity gradient. We reconstructed a dated phylogeny using 12 genes, to investigate the biogeographical history and diversification dynamics in the Colymbetinae. We aimed to identify the role that phylogenetic niche conservatism plays in the inversed diversification pattern seen in this group. Our results suggest that Colymbetinae originated in temperate climates, which supports the hypothesis that their distribution is the result of an ancestral adaptation to temperate environmental conditions rather than tropical origins, and that temperate niche conservatism can generate and/or maintain inverse latitudinal diversity gradients.

Adaptation and niche construction in human prehistory: a case study from the southern Scandinavian Late Glacial.

Science.gov (United States)

Riede, Felix

2011-03-27

The niche construction model postulates that human bio-social evolution is composed of three inheritance domains, genetic, cultural and ecological, linked by feedback selection. This paper argues that many kinds of archaeological data can serve as proxies for human niche construction processes, and presents a method for investigating specific niche construction hypotheses. To illustrate this method, the repeated emergence of specialized reindeer (Rangifer tarandus) hunting/herding economies during the Late Palaeolithic (ca 14.7-11.5 kyr BP) in southern Scandinavia is analysed from a niche construction/triple-inheritance perspective. This economic relationship resulted in the eventual domestication of Rangifer. The hypothesis of whether domestication was achieved as early as the Late Palaeolithic, and whether this required the use of domesticated dogs (Canis familiaris) as hunting, herding or transport aids, is tested via a comparative analysis using material culture-based phylogenies and ecological datasets in relation to demographic/genetic proxies. Only weak evidence for sustained niche construction behaviours by prehistoric hunter-gatherer in southern Scandinavia is found, but this study nonetheless provides interesting insights into the likely processes of dog and reindeer domestication, and into processes of adaptation in Late Glacial foragers.

Ecological niche transferability using invasive species as a case study.

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Miguel Fernández

Full Text Available Species distribution modeling is widely applied to predict invasive species distributions and species range shifts under climate change. Accurate predictions depend upon meeting the assumption that ecological niches are conserved, i.e., spatially or temporally transferable. Here we present a multi-taxon comparative analysis of niche conservatism using biological invasion events well documented in natural history museum collections. Our goal is to assess spatial transferability of the climatic niche of a range of noxious terrestrial invasive species using two complementary approaches. First we compare species' native versus invasive ranges in environmental space using two distinct methods, Principal Components Analysis and Mahalanobis distance. Second we compare species' native versus invaded ranges in geographic space as estimated using the species distribution modeling technique Maxent and the comparative index Hellinger's I. We find that species exhibit a range of responses, from almost complete transferability, in which the invaded niches completely overlap with the native niches, to a complete dissociation between native and invaded ranges. Intermediate responses included expansion of dimension attributable to either temperature or precipitation derived variables, as well as niche expansion in multiple dimensions. We conclude that the ecological niche in the native range is generally a poor predictor of invaded range and, by analogy, the ecological niche may be a poor predictor of range shifts under climate change. We suggest that assessing dimensions of niche transferability prior to standard species distribution modeling may improve the understanding of species' dynamics in the invaded range.

Target Article with Commentaries: Developmental Niche Construction

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Flynn, Emma G.; Laland, Kevin N.; Kendal, Rachel L.; Kendal, Jeremy R.

2013-01-01

Niche construction is the modification of components of the environment through an organism's activities. Humans modify their environments mainly through ontogenetic and cultural processes, and it is this reliance on learning, plasticity and culture that lends human niche construction a special potency. In this paper we aim to facilitate…

PCMO L01-Setting Specifications for Biological Investigational Medicinal Products.

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Krause, Stephan O

2015-01-01

This paper provides overall guidance and best practices for the setting of specifications for clinical biological drug substances and drug products within the framework of ICH guidelines on pharmaceutical development [Q8(R2) and Q11], quality risk management (Q9), and quality systems (Q10). A review is provided of the current regulatory expectations for the specification setting process as part of a control strategy during product development, pointing to existing challenges for the investigational new drug/investigational medicinal product dossier (IND/IMPD) sponsor. A case study illustrates how the investigational medicinal product specification revision process can be managed within a flexible quality system, and how specifications can be set and justified for early and late development stages. This paper provides an overview for the setting of product specifications for investigational medicinal products used in clinical trials. A case study illustrates how product specifications of investigational medicinal products can be justified and managed within a modern product quality system. © PDA, Inc. 2015.

Repression of Middle Sporulation Genes in Saccharomyces cerevisiae by the Sum1-Rfm1-Hst1 Complex Is Maintained by Set1 and H3K4 Methylation

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Jaiswal, Deepika; Jezek, Meagan; Quijote, Jeremiah; Lum, Joanna; Choi, Grace; Kulkarni, Rushmie; Park, DoHwan; Green, Erin M.

2017-01-01

The conserved yeast histone methyltransferase Set1 targets H3 lysine 4 (H3K4) for mono, di, and trimethylation and is linked to active transcription due to the euchromatic distribution of these methyl marks and the recruitment of Set1 during transcription. However, loss of Set1 results in increased expression of multiple classes of genes, including genes adjacent to telomeres and middle sporulation genes, which are repressed under normal growth conditions because they function in meiotic progression and spore formation. The mechanisms underlying Set1-mediated gene repression are varied, and still unclear in some cases, although repression has been linked to both direct and indirect action of Set1, associated with noncoding transcription, and is often dependent on the H3K4me2 mark. We show that Set1, and particularly the H3K4me2 mark, are implicated in repression of a subset of middle sporulation genes during vegetative growth. In the absence of Set1, there is loss of the DNA-binding transcriptional regulator Sum1 and the associated histone deacetylase Hst1 from chromatin in a locus-specific manner. This is linked to increased H4K5ac at these loci and aberrant middle gene expression. These data indicate that, in addition to DNA sequence, histone modification status also contributes to proper localization of Sum1. Our results also show that the role for Set1 in middle gene expression control diverges as cells receive signals to undergo meiosis. Overall, this work dissects an unexplored role for Set1 in gene-specific repression, and provides important insights into a new mechanism associated with the control of gene expression linked to meiotic differentiation. PMID:29066473

Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder

DEFF Research Database (Denmark)

Naaijen, Jill; Bralten, Janita; Poelmans, Geert

2017-01-01

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) often co-occur. Both are highly heritable; however, it has been difficult to discover genetic risk variants. Glutamate and GABA are main excitatory and inhibitory neurotransmitters in the brain; their balance...... within glutamatergic and GABAergic genes were investigated using the MAGMA software in an ADHD case-only sample (n=931), in which we assessed ASD symptoms and response inhibition on a Stop task. Gene set analysis for ADHD symptom severity, divided into inattention and hyperactivity/impulsivity symptoms...... is essential for proper brain development and functioning. In this study we investigated the role of glutamate and GABA genetics in ADHD severity, autism symptom severity and inhibitory performance, based on gene set analysis, an approach to investigate multiple genetic variants simultaneously. Common variants...

Shifts in the ecological niche of Lutzomyia peruensis under climate change scenarios in Peru.

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Moo-Llanes, D A; Arque-Chunga, W; Carmona-Castro, O; Yañez-Arenas, C; Yañez-Trujillano, H H; Cheverría-Pacheco, L; Baak-Baak, C M; Cáceres, A G

2017-06-01

The Peruvian Andes presents a climate suitable for many species of sandfly that are known vectors of leishmaniasis or bartonellosis, including Lutzomyia peruensis (Diptera: Psychodidae), among others. In the present study, occurrences data for Lu. peruensis were compiled from several items in the scientific literature from Peru published between 1927 and 2015. Based on these data, ecological niche models were constructed to predict spatial distributions using three algorithms [Support vector machine (SVM), the Genetic Algorithm for Rule-set Prediction (GARP) and Maximum Entropy (MaxEnt)]. In addition, the environmental requirements of Lu. peruensis and three niche characteristics were modelled in the context of future climate change scenarios: (a) potential changes in niche breadth; (b) shifts in the direction and magnitude of niche centroids, and (c) shifts in elevation range. The model identified areas that included environments suitable for Lu. peruensis in most regions of Peru (45.77%) and an average altitude of 3289 m a.s.l. Under climate change scenarios, a decrease in the distribution areas of Lu. peruensis was observed for all representative concentration pathways. However, the centroid of the species' ecological niche showed a northwest direction in all climate change scenarios. The information generated in this study may help health authorities responsible for the supervision of strategies to control leishmaniasis to coordinate, plan and implement appropriate strategies for each area of risk, taking into account the geographic distribution and potential dispersal of Lu. peruensis. © 2017 The Royal Entomological Society.

Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs.

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Winkler, Ingrid G; Sims, Natalie A; Pettit, Allison R; Barbier, Valérie; Nowlan, Bianca; Helwani, Falak; Poulton, Ingrid J; van Rooijen, Nico; Alexander, Kylie A; Raggatt, Liza J; Lévesque, Jean-Pierre

2010-12-02

In the bone marrow, hematopoietic stem cells (HSCs) reside in specific niches near osteoblast-lineage cells at the endosteum. To investigate the regulation of these endosteal niches, we studied the mobilization of HSCs into the bloodstream in response to granulocyte colony-stimulating factor (G-CSF). We report that G-CSF mobilization rapidly depletes endosteal osteoblasts, leading to suppressed endosteal bone formation and decreased expression of factors required for HSC retention and self-renewal. Importantly, G-CSF administration also depleted a population of trophic endosteal macrophages (osteomacs) that support osteoblast function. Osteomac loss, osteoblast suppression, and HSC mobilization occurred concomitantly, suggesting that osteomac loss could disrupt endosteal niches. Indeed, in vivo depletion of macrophages, in either macrophage Fas-induced apoptosis (Mafia) transgenic mice or by administration of clodronate-loaded liposomes to wild-type mice, recapitulated the: (1) loss of endosteal osteoblasts and (2) marked reduction of HSC-trophic cytokines at the endosteum, with (3) HSC mobilization into the blood, as observed during G-CSF administration. Together, these results establish that bone marrow macrophages are pivotal to maintain the endosteal HSC niche and that the loss of such macrophages leads to the egress of HSCs into the blood.

Global thermal niche models of two European grasses show high invasion risks in Antarctica.

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Pertierra, Luis R; Aragón, Pedro; Shaw, Justine D; Bergstrom, Dana M; Terauds, Aleks; Olalla-Tárraga, Miguel Ángel

2017-07-01

The two non-native grasses that have established long-term populations in Antarctica (Poa pratensis and Poa annua) were studied from a global multidimensional thermal niche perspective to address the biological invasion risk to Antarctica. These two species exhibit contrasting introduction histories and reproductive strategies and represent two referential case studies of biological invasion processes. We used a multistep process with a range of species distribution modelling techniques (ecological niche factor analysis, multidimensional envelopes, distance/entropy algorithms) together with a suite of thermoclimatic variables, to characterize the potential ranges of these species. Their native bioclimatic thermal envelopes in Eurasia, together with the different naturalized populations across continents, were compared next. The potential niche of P. pratensis was wider at the cold extremes; however, P. annua life history attributes enable it to be a more successful colonizer. We observe that particularly cold summers are a key aspect of the unique Antarctic environment. In consequence, ruderals such as P. annua can quickly expand under such harsh conditions, whereas the more stress-tolerant P. pratensis endures and persist through steady growth. Compiled data on human pressure at the Antarctic Peninsula allowed us to provide site-specific biosecurity risk indicators. We conclude that several areas across the region are vulnerable to invasions from these and other similar species. This can only be visualized in species distribution models (SDMs) when accounting for founder populations that reveal nonanalogous conditions. Results reinforce the need for strict management practices to minimize introductions. Furthermore, our novel set of temperature-based bioclimatic GIS layers for ice-free terrestrial Antarctica provide a mechanism for regional and global species distribution models to be built for other potentially invasive species. © 2017 John Wiley & Sons Ltd.

Chironomidae larvae (Diptera) of Neotropical floodplain: overlap niche in different habitats.

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Butakka, C M M; Ragonha, F H; Takeda, A M

2014-05-01

The niche overlap between trophic groups of Chironomidae larvae in different habitats was observed between trophic groups and between different environments in Neotropical floodplain. For the evaluation we used the index of niche overlap (CXY) and analysis of trophic networks, both from the types and amount of food items identified in the larval alimentary canal. In all environments, the larvae fed on mainly organic matter such as plants fragments and algae, but there were many omnivore larvae. Species that have high values of food items occurred in diverse environments as generalists with great overlap niche and those with a low amount of food items with less overlap niche were classified as specialists. The largest number of trophic niche overlap was observed among collector-gatherers in connected floodplain lakes. The lower values of index niche overlap were predators. The similarity in the diet of different taxa in the same niche does not necessarily imply competition between them, but coexistence when the food resource is not scarce in the environment even in partially overlapping niches.

GeneAnalytics: An Integrative Gene Set Analysis Tool for Next Generation Sequencing, RNAseq and Microarray Data.

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Ben-Ari Fuchs, Shani; Lieder, Iris; Stelzer, Gil; Mazor, Yaron; Buzhor, Ella; Kaplan, Sergey; Bogoch, Yoel; Plaschkes, Inbar; Shitrit, Alina; Rappaport, Noa; Kohn, Asher; Edgar, Ron; Shenhav, Liraz; Safran, Marilyn; Lancet, Doron; Guan-Golan, Yaron; Warshawsky, David; Shtrichman, Ronit

2016-03-01

Postgenomics data are produced in large volumes by life sciences and clinical applications of novel omics diagnostics and therapeutics for precision medicine. To move from "data-to-knowledge-to-innovation," a crucial missing step in the current era is, however, our limited understanding of biological and clinical contexts associated with data. Prominent among the emerging remedies to this challenge are the gene set enrichment tools. This study reports on GeneAnalytics™ ( geneanalytics.genecards.org ), a comprehensive and easy-to-apply gene set analysis tool for rapid contextualization of expression patterns and functional signatures embedded in the postgenomics Big Data domains, such as Next Generation Sequencing (NGS), RNAseq, and microarray experiments. GeneAnalytics' differentiating features include in-depth evidence-based scoring algorithms, an intuitive user interface and proprietary unified data. GeneAnalytics employs the LifeMap Science's GeneCards suite, including the GeneCards®--the human gene database; the MalaCards-the human diseases database; and the PathCards--the biological pathways database. Expression-based analysis in GeneAnalytics relies on the LifeMap Discovery®--the embryonic development and stem cells database, which includes manually curated expression data for normal and diseased tissues, enabling advanced matching algorithm for gene-tissue association. This assists in evaluating differentiation protocols and discovering biomarkers for tissues and cells. Results are directly linked to gene, disease, or cell "cards" in the GeneCards suite. Future developments aim to enhance the GeneAnalytics algorithm as well as visualizations, employing varied graphical display items. Such attributes make GeneAnalytics a broadly applicable postgenomics data analyses and interpretation tool for translation of data to knowledge-based innovation in various Big Data fields such as precision medicine, ecogenomics, nutrigenomics, pharmacogenomics, vaccinomics

Control of germline stem cell self-renewal and differentiation in the Drosophila ovary: concerted actions of niche signals and intrinsic factors.

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Xie, Ting

2013-01-01

In the Drosophila ovary, germline stem cells (GSCs) physically interact with their niche composed of terminal filament cells, cap cells, and possibly GSC-contacting escort cells (ECs). A GSC divides to generate a self-renewing stem cell that remains in the niche and a differentiating daughter that moves away from the niche. The GSC niche provides a bone morphogenetic protein (BMP) signal that maintains GSC self-renewal by preventing stem cell differentiation via repression of the differentiation-promoting gene bag of marbles (bam). In addition, it expresses E-cadherin, which mediates cell adhesion for anchoring GSCs in the niche, enabling continuous self-renewal. GSCs themselves also express different classes of intrinsic factors, including signal transducers, transcription factors, chromatin remodeling factors, translation regulators, and miRNAs, which control self-renewal by strengthening interactions with the niche and repressing various differentiation pathways. Differentiated GSC daughters, known as cystoblasts (CBs), also express distinct classes of intrinsic factors to inhibit self-renewal and promote germ cell differentiation. Surprisingly, GSC progeny are also dependent on their surrounding ECs for proper differentiation at least partly by preventing BMP from diffusing to the differentiated germ cell zone and by repressing ectopic BMP expression. Therefore, both GSC self-renewal and CB differentiation are controlled by collaborative actions of extrinsic signals and intrinsic factors. Copyright © 2012 Wiley Periodicals, Inc.

Comparative and functional genomics of the Lactococcus lactis taxon; insights into evolution and niche adaptation.

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Kelleher, Philip; Bottacini, Francesca; Mahony, Jennifer; Kilcawley, Kieran N; van Sinderen, Douwe

2017-03-29

Lactococcus lactis is among the most widely studied lactic acid bacterial species due to its long history of safe use and economic importance to the dairy industry, where it is exploited as a starter culture in cheese production. In the current study, we report on the complete sequencing of 16 L. lactis subsp. lactis and L. lactis subsp. cremoris genomes. The chromosomal features of these 16 L. lactis strains in conjunction with 14 completely sequenced, publicly available lactococcal chromosomes were assessed with particular emphasis on discerning the L. lactis subspecies division, evolution and niche adaptation. The deduced pan-genome of L. lactis was found to be closed, indicating that the representative data sets employed for this analysis are sufficient to fully describe the genetic diversity of the taxon. Niche adaptation appears to play a significant role in governing the genetic content of each L. lactis subspecies, while (differential) genome decay and redundancy in the dairy niche is also highlighted.

ADAGE signature analysis: differential expression analysis with data-defined gene sets.

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Tan, Jie; Huyck, Matthew; Hu, Dongbo; Zelaya, René A; Hogan, Deborah A; Greene, Casey S

2017-11-22

Gene set enrichment analysis and overrepresentation analyses are commonly used methods to determine the biological processes affected by a differential expression experiment. This approach requires biologically relevant gene sets, which are currently curated manually, limiting their availability and accuracy in many organisms without extensively curated resources. New feature learning approaches can now be paired with existing data collections to directly extract functional gene sets from big data. Here we introduce a method to identify perturbed processes. In contrast with methods that use curated gene sets, this approach uses signatures extracted from public expression data. We first extract expression signatures from public data using ADAGE, a neural network-based feature extraction approach. We next identify signatures that are differentially active under a given treatment. Our results demonstrate that these signatures represent biological processes that are perturbed by the experiment. Because these signatures are directly learned from data without supervision, they can identify uncurated or novel biological processes. We implemented ADAGE signature analysis for the bacterial pathogen Pseudomonas aeruginosa. For the convenience of different user groups, we implemented both an R package (ADAGEpath) and a web server ( http://adage.greenelab.com ) to run these analyses. Both are open-source to allow easy expansion to other organisms or signature generation methods. We applied ADAGE signature analysis to an example dataset in which wild-type and ∆anr mutant cells were grown as biofilms on the Cystic Fibrosis genotype bronchial epithelial cells. We mapped active signatures in the dataset to KEGG pathways and compared with pathways identified using GSEA. The two approaches generally return consistent results; however, ADAGE signature analysis also identified a signature that revealed the molecularly supported link between the MexT regulon and Anr. We designed

Cardiomyocyte-specific deletion of the G protein-coupled estrogen receptor (GPER) leads to left ventricular dysfunction and adverse remodeling: A sex-specific gene profiling analysis.

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Wang, Hao; Sun, Xuming; Chou, Jeff; Lin, Marina; Ferrario, Carlos M; Zapata-Sudo, Gisele; Groban, Leanne

2017-08-01

Activation of G protein-coupled estrogen receptor (GPER) by its agonist, G1, protects the heart from stressors such as pressure-overload, ischemia, a high-salt diet, estrogen loss, and aging, in various male and female animal models. Due to nonspecific effects of G1, the exact functions of cardiac GPER cannot be concluded from studies using systemic G1 administration. Moreover, global knockdown of GPER affects glucose homeostasis, blood pressure, and many other cardiovascular-related systems, thereby confounding interpretation of its direct cardiac actions. We generated a cardiomyocyte-specific GPER knockout (KO) mouse model to specifically investigate the functions of GPER in cardiomyocytes. Compared to wild type mice, cardiomyocyte-specific GPER KO mice exhibited adverse alterations in cardiac structure and impaired systolic and diastolic function, as measured by echocardiography. Gene deletion effects on left ventricular dimensions were more profound in male KO mice compared to female KO mice. Analysis of DNA microarray data from isolated cardiomyocytes of wild type and KO mice revealed sex-based differences in gene expression profiles affecting multiple transcriptional networks. Gene Set Enrichment Analysis (GSEA) revealed that mitochondrial genes are enriched in GPER KO females, whereas inflammatory response genes are enriched in GPER KO males, compared to their wild type counterparts of the same sex. The cardiomyocyte-specific GPER KO mouse model provides us with a powerful tool to study the functions of GPER in cardiomyocytes. The gene expression profiles of the GPER KO mice provide foundational information for further study of the mechanisms underlying sex-specific cardioprotection by GPER. Copyright © 2016 Elsevier B.V. All rights reserved.

Maternal Germline-Specific Genes in the Asian Malaria Mosquito Anopheles stephensi: Characterization and Application for Disease Control

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Biedler, James K.; Qi, Yumin; Pledger, David; Macias, Vanessa M.; James, Anthony A.; Tu, Zhijian

2014-01-01

Anopheles stephensi is a principal vector of urban malaria on the Indian subcontinent and an emerging model for molecular and genetic studies of mosquito biology. To enhance our understanding of female mosquito reproduction, and to develop new tools for basic research and for genetic strategies to control mosquito-borne infectious diseases, we identified 79 genes that displayed previtellogenic germline-specific expression based on RNA-Seq data generated from 11 life stage–specific and sex-specific samples. Analysis of this gene set provided insights into the biology and evolution of female reproduction. Promoters from two of these candidates, vitellogenin receptor and nanos, were used in independent transgenic cassettes for the expression of artificial microRNAs against suspected mosquito maternal-effect genes, discontinuous actin hexagon and myd88. We show these promoters have early germline-specific expression and demonstrate 73% and 42% knockdown of myd88 and discontinuous actin hexagon mRNA in ovaries 48 hr after blood meal, respectively. Additionally, we demonstrate maternal-specific delivery of mRNA and protein to progeny embryos. We discuss the application of this system of maternal delivery of mRNA/miRNA/protein in research on mosquito reproduction and embryonic development, and for the development of a gene drive system based on maternal-effect dominant embryonic arrest. PMID:25480960

UNTANGLING THE FUNGAL NICHE: A TRAIT-BASED APPROACH

Directory of Open Access Journals (Sweden)

Thomas W Crowther

2014-10-01

Full Text Available Fungi are prominent components of most terrestrial ecosystems, both in terms of biomass and ecosystem functioning, but the hyper-diverse nature of most communities has obscured the search for unifying principles governing community organization. In particular, unlike plants and animals, observational studies provide little evidence for the existence of niche processes in structuring fungal communities at broad spatial scales. This limits our capacity to predict how communities, and their functioning, vary across landscapes. We outline how a shift in focus, from taxonomy towards functional traits, might prove to be valuable in the search for general patterns in fungal ecology. We build on theoretical advances in plant and animal ecology to provide an empirical framework for a trait-based approach in fungal community ecology. Drawing upon specific characteristics of the fungal system, we highlight the significance of drought stress and combat in structuring free-living fungal communities. We propose a conceptual model to formalize how trade-offs between stress-tolerance and combative dominance are likely to organize communities across environmental gradients. Given that the survival of a fungus in a given environment is contingent on its ability to tolerate antagonistic competitors, measuring variation in combat trait expression along environmental gradients provides a means of elucidating realized, from fundamental niche spaces. We conclude that, using a trait-based understanding of how niche processes structure fungal communities across time and space, we can ultimately link communities with ecosystem functioning. Our trait-based framework highlights fundamental uncertainties that require testing in the fungal system, given their potential to uncover general mechanisms in fungal ecology.

Spermatogonial stem cell markers and niche in equids.

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Guilherme M J Costa

Full Text Available Spermatogonial stem cells (SSCs are the foundation of spermatogenesis and are located in a highly dynamic microenvironment called "niche" that influences all aspects of stem cell function, including homing, self-renewal and differentiation. Several studies have recently identified specific proteins that regulate the fate of SSCs. These studies also aimed at identifying surface markers that would facilitate the isolation of these cells in different vertebrate species. The present study is the first to investigate SSC physiology and niche in stallions and to offer a comparative evaluation of undifferentiated type A spermatogonia (Aund markers (GFRA1, PLZF and CSF1R in three different domestic equid species (stallions, donkeys, and mules. Aund were first characterized according to their morphology and expression of the GFRA1 receptor. Our findings strongly suggest that in stallions these cells were preferentially located in the areas facing the interstitium, particularly those nearby blood vessels. This distribution is similar to what has been observed in other vertebrate species. In addition, all three Aund markers were expressed in the equid species evaluated in this study. These markers have been well characterized in other mammalian species, which suggests that the molecular mechanisms that maintain the niche and Aund/SSCs physiology are conserved among mammals. We hope that our findings will help future studies needing isolation and cryopreservation of equids SSCs. In addition, our data will be very useful for studies that aim at preserving the germplasm of valuable animals, and involve germ cell transplantation or xenografts of equids testis fragments/germ cells suspensions.

Weak Evidence of Regeneration Habitat but Strong Evidence of Regeneration Niche for a Leguminous Shrub

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Delerue, Florian; Gonzalez, Maya; Michalet, Richard; Pellerin, Sylvain; Augusto, Laurent

2015-01-01

The identification of an ecological niche specific to the regeneration phase has mobilised significant attention. However, the importance of the regeneration niche concept remains unclear. Our main objective was to study the existence of such a regeneration niche for a leguminous shrub, Ulex europaeus. This study was carried out in southwest France in the context of water and nutrient stresses (mainly phosphorus limitation) due to the presence of nutrient-poor sandy soils. We analysed the regeneration of the species from the germination of seeds and emergence of new seedlings until the seedlings reached young shrub size. Our design included a P fertilisation treatment. We also investigated microsite characteristics (micro-topography and vegetation development) as they can interact with meteorological conditions and determine water availability for seeds and seedlings. We found that P availability controlled seedling growth and the time necessary to reach young shrub size. Water availability appeared to impact the species germination and seedlings survival. We also found that P and water availability depended on the interactions between microsite characteristics and climatic variations. Finally we found evidence that P and water availability are important ecological factors shaping the regeneration niche of the species, but we found weak evidence that any microsite would be appropriate for the regeneration of the species in the long term. Future studies regarding regeneration niches need to distinguish more clearly the ecological factors important for regeneration (the regeneration niche per se) and the physical world where the seedlings appear and develop (the regeneration habitat). PMID:26098877

Weak Evidence of Regeneration Habitat but Strong Evidence of Regeneration Niche for a Leguminous Shrub.

Directory of Open Access Journals (Sweden)

Florian Delerue

Full Text Available The identification of an ecological niche specific to the regeneration phase has mobilised significant attention. However, the importance of the regeneration niche concept remains unclear. Our main objective was to study the existence of such a regeneration niche for a leguminous shrub, Ulex europaeus. This study was carried out in southwest France in the context of water and nutrient stresses (mainly phosphorus limitation due to the presence of nutrient-poor sandy soils. We analysed the regeneration of the species from the germination of seeds and emergence of new seedlings until the seedlings reached young shrub size. Our design included a P fertilisation treatment. We also investigated microsite characteristics (micro-topography and vegetation development as they can interact with meteorological conditions and determine water availability for seeds and seedlings. We found that P availability controlled seedling growth and the time necessary to reach young shrub size. Water availability appeared to impact the species germination and seedlings survival. We also found that P and water availability depended on the interactions between microsite characteristics and climatic variations. Finally we found evidence that P and water availability are important ecological factors shaping the regeneration niche of the species, but we found weak evidence that any microsite would be appropriate for the regeneration of the species in the long term. Future studies regarding regeneration niches need to distinguish more clearly the ecological factors important for regeneration (the regeneration niche per se and the physical world where the seedlings appear and develop (the regeneration habitat.

Human apolipoprotein CIII gene expression is regulated by positive and negative cis-acting elements and tissue-specific protein factors

International Nuclear Information System (INIS)

Reue, K.; Leff, T.; Breslow, J.L.

1988-01-01

Apolipoprotein CIII (apoCIII) is a major protein constituent of triglyceride-rich lipoproteins and is synthesized primarily in the liver. Cis-acting DNA elements required for liver-specific apoCIII gene transcription were identified with transient expression assays in the human hepatoma (HepG2) and epithelial carcinoma (HeLa) cell lines. In liver cells, 821 nucleotides of the human apoCIII gene 5'-flanking sequence were required for maximum levels of gene expression, while the proximal 110 nucleotides alone were sufficient. No expression was observed in similar studies with HeLa cells. The level of expression was modulated by a combination of positive and negative cis-acting sequences, which interact with distinct sets of proteins from liver and HeLa cell nuclear extracts. The proximal positive regulatory region shares homology with similarly located sequences of other genes strongly expressed in the liver, including α 1 -antitrypsin and other apolipoprotein genes. The negative regulatory region is striking homologous to the human β-interferon gene regulatory element. The distal positive region shares homology with some viral enhancers and has properties of a tissue-specific enhancer. The regulation of the apoCIII gene is complex but shares features with other genes, suggesting shuffling of regulatory elements as a common mechanism for cell type-specific gene expression

CAsubtype: An R Package to Identify Gene Sets Predictive of Cancer Subtypes and Clinical Outcomes.

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Kong, Hualei; Tong, Pan; Zhao, Xiaodong; Sun, Jielin; Li, Hua

2018-03-01

In the past decade, molecular classification of cancer has gained high popularity owing to its high predictive power on clinical outcomes as compared with traditional methods commonly used in clinical practice. In particular, using gene expression profiles, recent studies have successfully identified a number of gene sets for the delineation of cancer subtypes that are associated with distinct prognosis. However, identification of such gene sets remains a laborious task due to the lack of tools with flexibility, integration and ease of use. To reduce the burden, we have developed an R package, CAsubtype, to efficiently identify gene sets predictive of cancer subtypes and clinical outcomes. By integrating more than 13,000 annotated gene sets, CAsubtype provides a comprehensive repertoire of candidates for new cancer subtype identification. For easy data access, CAsubtype further includes the gene expression and clinical data of more than 2000 cancer patients from TCGA. CAsubtype first employs principal component analysis to identify gene sets (from user-provided or package-integrated ones) with robust principal components representing significantly large variation between cancer samples. Based on these principal components, CAsubtype visualizes the sample distribution in low-dimensional space for better understanding of the distinction between samples and classifies samples into subgroups with prevalent clustering algorithms. Finally, CAsubtype performs survival analysis to compare the clinical outcomes between the identified subgroups, assessing their clinical value as potentially novel cancer subtypes. In conclusion, CAsubtype is a flexible and well-integrated tool in the R environment to identify gene sets for cancer subtype identification and clinical outcome prediction. Its simple R commands and comprehensive data sets enable efficient examination of the clinical value of any given gene set, thus facilitating hypothesis generating and testing in biological and

Organ-specific gene expression: the bHLH protein Sage provides tissue specificity to Drosophila FoxA.

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Fox, Rebecca M; Vaishnavi, Aria; Maruyama, Rika; Andrew, Deborah J

2013-05-01

FoxA transcription factors play major roles in organ-specific gene expression, regulating, for example, glucagon expression in the pancreas, GLUT2 expression in the liver, and tyrosine hydroxylase expression in dopaminergic neurons. Organ-specific gene regulation by FoxA proteins is achieved through cooperative regulation with a broad array of transcription factors with more limited expression domains. Fork head (Fkh), the sole Drosophila FoxA family member, is required for the development of multiple distinct organs, yet little is known regarding how Fkh regulates tissue-specific gene expression. Here, we characterize Sage, a bHLH transcription factor expressed exclusively in the Drosophila salivary gland (SG). We show that Sage is required for late SG survival and normal tube morphology. We find that many Sage targets, identified by microarray analysis, encode SG-specific secreted cargo, transmembrane proteins, and the enzymes that modify these proteins. We show that both Sage and Fkh are required for the expression of Sage target genes, and that co-expression of Sage and Fkh is sufficient to drive target gene expression in multiple cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage-Fkh targets, and Sage, Fkh and Sens colocalize on SG chromosomes. Importantly, expression of Sage-Fkh target genes appears to simply add to the tissue-specific gene expression programs already established in other cell types, and Sage and Fkh cannot alter the fate of most embryonic cell types even when expressed early and continuously.

Niche construction drives social dependence in hermit crabs.

Science.gov (United States)

Laidre, Mark E

2012-10-23

Organisms can receive not only a genetic inheritance from their ancestors but also an ecological inheritance, involving modifications their ancestors made to the environment through niche construction. Ecological inheritances may persist as a legacy, potentially generating selection pressures that favor sociality. Yet, most proposed cases of sociality being impacted by an ecological inheritance come from organisms that live among close kin and were highly social before their niche construction began. Here, I show that in terrestrial hermit crabs (Coenobita compressus)--organisms that do not live with kin and reside alone, each in its own shell--niche-construction drives social dependence, such that individuals can only survive in remodeled shells handed down from conspecifics. These results suggest that niche construction can be an important initiator of evolutionary pressures to socialize, even among unrelated and otherwise asocial organisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

Stem cell dynamics in the hair follicle niche

Science.gov (United States)

Rompolas, Panteleimon; Greco, Valentina

2014-01-01

Hair follicles are skin appendages of the mammalian skin that have the ability to periodically and stereotypically regenerate in order to continuously produce new hair over our lifetime. The ability of the hair follicle to regenerate is due to the presence of stem cells that along with other cell populations and non-cellular components, including molecular signals and extracellular material, make up a niche microenvironment. Mounting evidence suggests that the niche is critical for regulating stem cell behavior and thus the process of regeneration. Here we review the literature concerning past and current studies that have utilized mouse genetic models, combined with other approaches to dissect the molecular and cellular composition of the hair follicle niche. We also discuss our current understanding of how stem cells operate within the niche during the process of tissue regeneration and the factors that regulate their behavior. PMID:24361866

Three gene expression vector sets for concurrently expressing multiple genes in Saccharomyces cerevisiae.

Science.gov (United States)

Ishii, Jun; Kondo, Takashi; Makino, Harumi; Ogura, Akira; Matsuda, Fumio; Kondo, Akihiko

2014-05-01

Yeast has the potential to be used in bulk-scale fermentative production of fuels and chemicals due to its tolerance for low pH and robustness for autolysis. However, expression of multiple external genes in one host yeast strain is considerably labor-intensive due to the lack of polycistronic transcription. To promote the metabolic engineering of yeast, we generated systematic and convenient genetic engineering tools to express multiple genes in Saccharomyces cerevisiae. We constructed a series of multi-copy and integration vector sets for concurrently expressing two or three genes in S. cerevisiae by embedding three classical promoters. The comparative expression capabilities of the constructed vectors were monitored with green fluorescent protein, and the concurrent expression of genes was monitored with three different fluorescent proteins. Our multiple gene expression tool will be helpful to the advanced construction of genetically engineered yeast strains in a variety of research fields other than metabolic engineering. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Meta-analysis of differentiating mouse embryonic stem cell gene expression kinetics reveals early change of a small gene set.

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Clive H Glover

2006-11-01

Full Text Available Stem cell differentiation involves critical changes in gene expression. Identification of these should provide endpoints useful for optimizing stem cell propagation as well as potential clues about mechanisms governing stem cell maintenance. Here we describe the results of a new meta-analysis methodology applied to multiple gene expression datasets from three mouse embryonic stem cell (ESC lines obtained at specific time points during the course of their differentiation into various lineages. We developed methods to identify genes with expression changes that correlated with the altered frequency of functionally defined, undifferentiated ESC in culture. In each dataset, we computed a novel statistical confidence measure for every gene which captured the certainty that a particular gene exhibited an expression pattern of interest within that dataset. This permitted a joint analysis of the datasets, despite the different experimental designs. Using a ranking scheme that favored genes exhibiting patterns of interest, we focused on the top 88 genes whose expression was consistently changed when ESC were induced to differentiate. Seven of these (103728_at, 8430410A17Rik, Klf2, Nr0b1, Sox2, Tcl1, and Zfp42 showed a rapid decrease in expression concurrent with a decrease in frequency of undifferentiated cells and remained predictive when evaluated in additional maintenance and differentiating protocols. Through a novel meta-analysis, this study identifies a small set of genes whose expression is useful for identifying changes in stem cell frequencies in cultures of mouse ESC. The methods and findings have broader applicability to understanding the regulation of self-renewal of other stem cell types.

Synergistic selection between ecological niche and mate preference primes diversification.

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Boughman, Janette W; Svanbäck, Richard

2017-01-01

The ecological niche and mate preferences have independently been shown to be important for the process of speciation. Here, we articulate a novel mechanism by which ecological niche use and mate preference can be linked to promote speciation. The degree to which individual niches are narrow and clustered affects the strength of divergent natural selection and population splitting. Similarly, the degree to which individual mate preferences are narrow and clustered affects the strength of divergent sexual selection and assortative mating between diverging forms. This novel perspective is inspired by the literature on ecological niches; it also explores mate preferences and how they may contribute to speciation. Unlike much comparative work, we do not search for evolutionary patterns using proxies for adaptation and sexual selection, but rather we elucidate how ideas from niche theory relate to mate preference, and how this relationship can foster speciation. Recognizing that individual and population niches are conceptually and ecologically linked to individual and population mate preference functions will significantly increase our understanding of rapid evolutionary diversification in nature. It has potential to help solve the difficult challenge of testing the role of sexual selection in the speciation process. We also identify ecological factors that are likely to affect individual niche and individual mate preference in synergistic ways and as a consequence to promote speciation. The ecological niche an individual occupies can directly affect its mate preference. Clusters of individuals with narrow, differentiated niches are likely to have narrow, differentiated mate preference functions. Our approach integrates ecological and sexual selection research to further our understanding of diversification processes. Such integration may be necessary for progress because these processes seem inextricably linked in the natural world. © 2016 The Author(s). Evolution �

Geological 3D model of the investigation niche in ONKALO, Olkiluoto, southwestern Finland

Energy Technology Data Exchange (ETDEWEB)

Koittola, N.

2014-07-15

The main goal of this Master of Science Thesis was to create a geological 3D-model of the investigation niche 3 and its surroundings. The model were created for the needs of the rock mechanical back analysis. This study is a part of Posiva's regional studies for characterization of the bedrock. Totally 4 models were created: lithological model, foliation model, fracture model, and physical rock property model. Besides the modeling, there was also made a study of the migmatite structures in the niche. Used geological and geophysical methods were drill core loggings, tunnel mapping, ground penetration radar, mise-a-la-masse and drill hole geophysics. Four rock types exist at the niche area: veined gneiss, pegmatite granite, diatexitic gneiss and quartz gneiss. The lithological units were modeled primary with the drill core loggings, tunnel mapping and ground penetrating radar. The major lithological units followed the main foliation direction (south dipping). So the continuations were fairly easy to model in the walls and roof, where the data was lacking. Foliation and fractures were modeled as discs, with mid-points at the measurement points of the structure. There were two main foliation directions 164/46 and 62/39. Fractures were more scattered but three fracture sets can be separated: 156/34, 270/85 and 342/83. The first set is mainly from the drill core loggings, second and third from tunnel mapping. Used methods in foliation model were drill core loggings, tunnel mapping and drill hole geophysics. In fracture model used data was from drill core loggings, tunnel mapping, mise-a-la-masse measurements and drill core geophysic. Four anomalous zones were detected with the drill hole geophysics. Three of these zones were associated with intensely fractured zones and one was connected to exceptionally high mica content in the gneiss. Rocks of Olkiluoto are divided into gneisses and magmatic rocks in the geological mapping. Actually almost all Olkiluoto

Geological 3D model of the investigation niche in ONKALO, Olkiluoto, southwestern Finland

International Nuclear Information System (INIS)

Koittola, N.

2014-07-01

The main goal of this Master of Science Thesis was to create a geological 3D-model of the investigation niche 3 and its surroundings. The model were created for the needs of the rock mechanical back analysis. This study is a part of Posiva's regional studies for characterization of the bedrock. Totally 4 models were created: lithological model, foliation model, fracture model, and physical rock property model. Besides the modeling, there was also made a study of the migmatite structures in the niche. Used geological and geophysical methods were drill core loggings, tunnel mapping, ground penetration radar, mise-a-la-masse and drill hole geophysics. Four rock types exist at the niche area: veined gneiss, pegmatite granite, diatexitic gneiss and quartz gneiss. The lithological units were modeled primary with the drill core loggings, tunnel mapping and ground penetrating radar. The major lithological units followed the main foliation direction (south dipping). So the continuations were fairly easy to model in the walls and roof, where the data was lacking. Foliation and fractures were modeled as discs, with mid-points at the measurement points of the structure. There were two main foliation directions 164/46 and 62/39. Fractures were more scattered but three fracture sets can be separated: 156/34, 270/85 and 342/83. The first set is mainly from the drill core loggings, second and third from tunnel mapping. Used methods in foliation model were drill core loggings, tunnel mapping and drill hole geophysics. In fracture model used data was from drill core loggings, tunnel mapping, mise-a-la-masse measurements and drill core geophysic. Four anomalous zones were detected with the drill hole geophysics. Three of these zones were associated with intensely fractured zones and one was connected to exceptionally high mica content in the gneiss. Rocks of Olkiluoto are divided into gneisses and magmatic rocks in the geological mapping. Actually almost all Olkiluoto's rocks are

Reproductive Interference and Niche Partitioning in Aphidophagous Insects

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Suzuki Noriyuki

2016-01-01

Full Text Available The range and quality of prey species differ greatly among closely related species of predators. However, the factors responsible for this diversified niche utilization are unclear. This is because the predation and resource competition do not always prevent species coexistence. In this paper, we present evidence in support of reproductive interference as a driver of niche partitioning, focusing on aphidophagous insect. Firstly, we present closely related generalist and specialist species pairs in aphidophagous lacewings to compare the reproductive interference hypothesis with two other hypotheses that have been proposed to explain niche partitioning in lacewings and sympatric speciation through host race formation and sexual selection. Secondly, we present a case study that shows how reproductive interference can drive niche partitioning in sibling ladybird species. Thirdly, we show that many ladybird genera include species inhabiting the same region but having different food and habitat preferences, raising the possibility that reproductive interference might occur in these groups. Finally, we show that intraguild predation cannot always explain the niche partitioning in aphidophagous insects including hoverflies and parasitoids. On the basis of the evidence presented, we urge that future studies investigating predator communities should take account of the role of reproductive interference.

Professional Niche Differentiation: Understanding Dai (Traditional Midwife Survival in Rural Rajasthan

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Sharmeen Azher

2017-04-01

Full Text Available Prescribing medicine, providing contraception, delivering babies – although we may turn to physicians, rural Rajasthani women turn to Barefoot Doctors out of necessity. Such care is available courtesy of the Barefoot College, a pioneering NGO that transforms the skills of the illiterate poor into local infrastructure. Barefoot Doctors are innovative because of their origins as dais (traditional midwives; once abundant across South Asia, dais are mostly extinct due to government/NGO interventions emphasizing “modernity”, like the Accredited Social Health Activist program. Why, then, have dais survived as Barefoot Doctors when they are extinct elsewhere? Ecological niche differentiation refers to when competing species successfully coexist; one species adapts to fulfill another role. Using over fifty interviews with stakeholders, I explain the persistence of Barefoot Doctors as health resources using “professional niche differentiation”. Barefoot Doctors exemplify how health infrastructure can be sustainable in resource-poor settings when created according to local needs and ideologies.

The impact of niche green developments in transforming the building sector: The case study of Lochiel Park

International Nuclear Information System (INIS)

Berry, Stephen; Davidson, Kathryn; Saman, Wasim

2013-01-01

Energy use in residential buildings is a significant contributor to global carbon emissions. The South Australian Government responded to concern for anthropogenic greenhouse gas emissions by creating a model development of near zero energy homes in a near zero carbon impact estate. The creation of the Lochiel Park Green Village challenged a collective of industry experts and policy makers to set objectives, performance targets and regulatory guidelines outside existing institutional and professional norms. Literature suggests that the creation of niche events can help the transition away from dominant technologies, practices and beliefs, and lead to organisations embracing new tools, construction practices, technologies, standards and policies. By applying a multi-level socio-technical framework, and utilising evidence collected from a series of interviews with key government and industry leaders, this paper examines how, under the influence of landscape pressures, structural change at the regime level can come from the incubation of ideas and experiences at the niche level. The available evidence finds that the creation of the Lochiel Park Green Village has allowed many individuals and organisations to gain a more detailed and practical understanding of sustainable housing, and has given organisations the confidence to change industry practices, government policies, and regulatory standards. -- Highlights: •We examined the impact of creating a net zero carbon residential development. •Structural change can come from incubation of experiences at the niche level. •Significant barriers to sustainability can be overcome through leadership. •Performance targets were set outside existing institutional and professional norms. •Niche events help transition from dominant technologies, practices and beliefs

Are species' responses to global change predicted by past niche evolution?

Science.gov (United States)

Lavergne, Sébastien; Evans, Margaret E. K.; Burfield, Ian J.; Jiguet, Frederic; Thuiller, Wilfried

2013-01-01

Predicting how and when adaptive evolution might rescue species from global change, and integrating this process into tools of biodiversity forecasting, has now become an urgent task. Here, we explored whether recent population trends of species can be explained by their past rate of niche evolution, which can be inferred from increasingly available phylogenetic and niche data. We examined the assemblage of 409 European bird species for which estimates of demographic trends between 1970 and 2000 are available, along with a species-level phylogeny and data on climatic, habitat and trophic niches. We found that species' proneness to demographic decline is associated with slow evolution of the habitat niche in the past, in addition to certain current-day life-history and ecological traits. A similar result was found at a higher taxonomic level, where families prone to decline have had a history of slower evolution of climatic and habitat niches. Our results support the view that niche conservatism can prevent some species from coping with environmental change. Thus, linking patterns of past niche evolution and contemporary species dynamics for large species samples may provide insights into how niche evolution may rescue certain lineages in the face of global change. PMID:23209172

Dissecting specific and global transcriptional regulation of bacterial gene expression

NARCIS (Netherlands)

Gerosa, Luca; Kochanowski, Karl; Heinemann, Matthias; Sauer, Uwe

Gene expression is regulated by specific transcriptional circuits but also by the global expression machinery as a function of growth. Simultaneous specific and global regulation thus constitutes an additional-but often neglected-layer of complexity in gene expression. Here, we develop an

A hypothesis-testing framework for studies investigating ontogenetic niche shifts using stable isotope ratios.

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Caroline M Hammerschlag-Peyer

Full Text Available Ontogenetic niche shifts occur across diverse taxonomic groups, and can have critical implications for population dynamics, community structure, and ecosystem function. In this study, we provide a hypothesis-testing framework combining univariate and multivariate analyses to examine ontogenetic niche shifts using stable isotope ratios. This framework is based on three distinct ontogenetic niche shift scenarios, i.e., (1 no niche shift, (2 niche expansion/reduction, and (3 discrete niche shift between size classes. We developed criteria for identifying each scenario, as based on three important resource use characteristics, i.e., niche width, niche position, and niche overlap. We provide an empirical example for each ontogenetic niche shift scenario, illustrating differences in resource use characteristics among different organisms. The present framework provides a foundation for future studies on ontogenetic niche shifts, and also can be applied to examine resource variability among other population sub-groupings (e.g., by sex or phenotype.

Niche evolution and diversification in a Neotropical radiation of birds (Aves: Furnariidae).

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Seeholzer, Glenn F; Claramunt, Santiago; Brumfield, Robb T

2017-03-01

Rapid diversification may be caused by ecological adaptive radiation via niche divergence. In this model, speciation is coupled with niche divergence and lineage diversification is predicted to be correlated with rates of niche evolution. Studies of the role of niche evolution in diversification have generally focused on ecomorphological diversification but climatic-niche evolution may also be important. We tested these alternatives using a phylogeny of 298 species of ovenbirds (Aves: Furnariidae). We found that within Furnariidae, variation in species richness and diversification rates of subclades were best predicted by rate of climatic-niche evolution than ecomorphological evolution. Although both are clearly important, univariate regression and multivariate model averaging more consistently supported the climatic-niche as the best predictor of lineage diversification. Our study adds to the growing body of evidence, suggesting that climatic-niche divergence may be an important driver of rapid diversification in addition to ecomorphological evolution. However, this pattern may depend on the phylogenetic scale at which rate heterogeneity is examined. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Description of electrophoretic loci and tissue specific gene ...

African Journals Online (AJOL)

Protein electrophoresis was used to study the distributions and tissue specificity of gene expression of enzymes encoded by 42 loci in Rhinolophus clivosus and R. landeri, the genetically most divergent of the ten species of southern African horseshoe bats. No differences in gene expression were found between R.

Genome‐scale diversity and niche adaptation analysis of Lactococcus lactis by comparative genome hybridization using multi‐strain arrays

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Siezen, Roland J.; Bayjanov, Jumamurat R.; Felis, Giovanna E.; van der Sijde, Marijke R.; Starrenburg, Marjo; Molenaar, Douwe; Wels, Michiel; van Hijum, Sacha A. F. T.; van Hylckama Vlieg, Johan E. T.

2011-01-01

Summary Lactococcus lactis produces lactic acid and is widely used in the manufacturing of various fermented dairy products. However, the species is also frequently isolated from non‐dairy niches, such as fermented plant material. Recently, these non‐dairy strains have gained increasing interest, as they have been described to possess flavour‐forming activities that are rarely found in dairy isolates and have diverse metabolic properties. We performed an extensive whole‐genome diversity analysis on 39 L. lactis strains, isolated from dairy and plant sources. Comparative genome hybridization analysis with multi‐strain microarrays was used to assess presence or absence of genes and gene clusters in these strains, relative to all L. lactis sequences in public databases, whereby chromosomal and plasmid‐encoded genes were computationally analysed separately. Nearly 3900 chromosomal orthologous groups (chrOGs) were defined on basis of four sequenced chromosomes of L. lactis strains (IL1403, KF147, SK11, MG1363). Of these, 1268 chrOGs are present in at least 35 strains and represent the presently known core genome of L. lactis, and 72 chrOGs appear to be unique for L. lactis. Nearly 600 and 400 chrOGs were found to be specific for either the subspecies lactis or subspecies cremoris respectively. Strain variability was found in presence or absence of gene clusters related to growth on plant substrates, such as genes involved in the consumption of arabinose, xylan, α‐galactosides and galacturonate. Further niche‐specific differences were found in gene clusters for exopolysaccharides biosynthesis, stress response (iron transport, osmotolerance) and bacterial defence mechanisms (nisin biosynthesis). Strain variability of functions encoded on known plasmids included proteolysis, lactose fermentation, citrate uptake, metal ion resistance and exopolysaccharides biosynthesis. The present study supports the view of L. lactis as a species with a very flexible

Horizontal gene transfer between bacteria.

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Heuer, Holger; Smalla, Kornelia

2007-01-01

Horizontal gene transfer (HGT) refers to the acquisition of foreign genes by organisms. The occurrence of HGT among bacteria in the environment is assumed to have implications in the risk assessment of genetically modified bacteria which are released into the environment. First, introduced genetic sequences from a genetically modified bacterium could be transferred to indigenous micro-organisms and alter their genome and subsequently their ecological niche. Second, the genetically modified bacterium released into the environment might capture mobile genetic elements (MGE) from indigenous micro-organisms which could extend its ecological potential. Thus, for a risk assessment it is important to understand the extent of HGT and genome plasticity of bacteria in the environment. This review summarizes the present state of knowledge on HGT between bacteria as a crucial mechanism contributing to bacterial adaptability and diversity. In view of the use of GM crops and microbes in agricultural settings, in this mini-review we focus particularly on the presence and role of MGE in soil and plant-associated bacteria and the factors affecting gene transfer.

Probabilistic and spatially variable niches inferred from demography

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Jeffrey M. Diez; Itamar Giladi; Robert Warren; H. Ronald. Pulliam

2014-01-01

Summary 1. Mismatches between species distributions and habitat suitability are predicted by niche theory and have important implications for forecasting how species may respond to environmental changes. Quantifying these mismatches is challenging, however, due to the high dimensionality of species niches and the large spatial and temporal variability in population...

Gene set-based module discovery in the breast cancer transcriptome

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Zhang Michael Q

2009-02-01

Full Text Available Abstract Background Although microarray-based studies have revealed global view of gene expression in cancer cells, we still have little knowledge about regulatory mechanisms underlying the transcriptome. Several computational methods applied to yeast data have recently succeeded in identifying expression modules, which is defined as co-expressed gene sets under common regulatory mechanisms. However, such module discovery methods are not applied cancer transcriptome data. Results In order to decode oncogenic regulatory programs in cancer cells, we developed a novel module discovery method termed EEM by extending a previously reported module discovery method, and applied it to breast cancer expression data. Starting from seed gene sets prepared based on cis-regulatory elements, ChIP-chip data, and gene locus information, EEM identified 10 principal expression modules in breast cancer based on their expression coherence. Moreover, EEM depicted their activity profiles, which predict regulatory programs in each subtypes of breast tumors. For example, our analysis revealed that the expression module regulated by the Polycomb repressive complex 2 (PRC2 is downregulated in triple negative breast cancers, suggesting similarity of transcriptional programs between stem cells and aggressive breast cancer cells. We also found that the activity of the PRC2 expression module is negatively correlated to the expression of EZH2, a component of PRC2 which belongs to the E2F expression module. E2F-driven EZH2 overexpression may be responsible for the repression of the PRC2 expression modules in triple negative tumors. Furthermore, our network analysis predicts regulatory circuits in breast cancer cells. Conclusion These results demonstrate that the gene set-based module discovery approach is a powerful tool to decode regulatory programs in cancer cells.

High-throughput analysis of candidate imprinted genes and allele-specific gene expression in the human term placenta

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Clark Taane G

2010-04-01

Full Text Available Abstract Background Imprinted genes show expression from one parental allele only and are important for development and behaviour. This extreme mode of allelic imbalance has been described for approximately 56 human genes. Imprinting status is often disrupted in cancer and dysmorphic syndromes. More subtle variation of gene expression, that is not parent-of-origin specific, termed 'allele-specific gene expression' (ASE is more common and may give rise to milder phenotypic differences. Using two allele-specific high-throughput technologies alongside bioinformatics predictions, normal term human placenta was screened to find new imprinted genes and to ascertain the extent of ASE in this tissue. Results Twenty-three family trios of placental cDNA, placental genomic DNA (gDNA and gDNA from both parents were tested for 130 candidate genes with the Sequenom MassArray system. Six genes were found differentially expressed but none imprinted. The Illumina ASE BeadArray platform was then used to test 1536 SNPs in 932 genes. The array was enriched for the human orthologues of 124 mouse candidate genes from bioinformatics predictions and 10 human candidate imprinted genes from EST database mining. After quality control pruning, a total of 261 informative SNPs (214 genes remained for analysis. Imprinting with maternal expression was demonstrated for the lymphocyte imprinted gene ZNF331 in human placenta. Two potential differentially methylated regions (DMRs were found in the vicinity of ZNF331. None of the bioinformatically predicted candidates tested showed imprinting except for a skewed allelic expression in a parent-specific manner observed for PHACTR2, a neighbour of the imprinted PLAGL1 gene. ASE was detected for two or more individuals in 39 candidate genes (18%. Conclusions Both Sequenom and Illumina assays were sensitive enough to study imprinting and strong allelic bias. Previous bioinformatics approaches were not predictive of new imprinted genes

Niche conservatism of Eulophia alta, a trans-Atlantic orchid species

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Marta Kolanowska

2014-03-01

Full Text Available The genus Eulophia embraces over 230 species distributed through the tropical and subtropical Africa, Asia, Australia and the Americas. In Neotropics it is represented by a sole species – E. alta. The aim of the presented study was to evaluate the difference between ecological niches occupied by American and African populations of this species based on the ecological niche modeling. The similarity between the glacial and present niches occupied by E. alta was calculated and the factors limiting the species occurrence were identified. Areas of seasonal tropical forest, tropical savanna and woodland served as refugia for the studied species during last glacial maximum and they were more widespread in Neotropics than in Africa. No significant niche shift after last glacial maximum was observed. The distribution of E. alta in its whole range is restricted mainly by temperature seasonality. The differences in the niches occupied by African and Neotropical populations of E. alta suggest preglacial disjunction of the species range and independent adaptation of both groups. Despite the significant range disjunction of E. alta the species is characterized by relatively high degree of niche conservatism.

A Comparative Pan-Genome Perspective of Niche-Adaptable Cell-Surface Protein Phenotypes in Lactobacillus rhamnosus

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Kant, Ravi; Sigvart-Mattila, Pia; Paulin, Lars; Mecklin, Jukka-Pekka; Saarela, Maria; Palva, Airi; von Ossowski, Ingemar

2014-01-01

Lactobacillus rhamnosus is a ubiquitously adaptable Gram-positive bacterium and as a typical commensal can be recovered from various microbe-accessible bodily orifices and cavities. Then again, other isolates are food-borne, with some of these having been long associated with naturally fermented cheeses and yogurts. Additionally, because of perceived health benefits to humans and animals, numerous L. rhamnosus strains have been selected for use as so-called probiotics and are often taken in the form of dietary supplements and functional foods. At the genome level, it is anticipated that certain genetic variances will have provided the niche-related phenotypes that augment the flexible adaptiveness of this species, thus enabling its strains to grow and survive in their respective host environments. For this present study, we considered it functionally informative to examine and catalogue the genotype-phenotype variation existing at the cell surface between different L. rhamnosus strains, with the presumption that this might be relatable to habitat preferences and ecological adaptability. Here, we conducted a pan-genomic study involving 13 genomes from L. rhamnosus isolates with various origins. In using a benchmark strain (gut-adapted L. rhamnosus GG) for our pan-genome comparison, we had focused our efforts on a detailed examination and description of gene products for certain functionally relevant surface-exposed proteins, each of which in effect might also play a part in niche adaptability among the other strains. Perhaps most significantly of the surface protein loci we had analyzed, it would appear that the spaCBA operon (known to encode SpaCBA-called pili having a mucoadhesive phenotype) is a genomic rarity and an uncommon occurrence in L. rhamnosus. However, for any of the so-piliated L. rhamnosus strains, they will likely possess an increased niche-specific fitness, which functionally might presumably be manifested by a protracted transient colonization of

Lactobacillus plantarum gene clusters encoding putative cell-surface protein complexes for carbohydrate utilization are conserved in specific gram-positive bacteria

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Muscariello Lidia

2006-05-01

Full Text Available Abstract Background Genomes of gram-positive bacteria encode many putative cell-surface proteins, of which the majority has no known function. From the rapidly increasing number of available genome sequences it has become apparent that many cell-surface proteins are conserved, and frequently encoded in gene clusters or operons, suggesting common functions, and interactions of multiple components. Results A novel gene cluster encoding exclusively cell-surface proteins was identified, which is conserved in a subgroup of gram-positive bacteria. Each gene cluster generally has one copy of four new gene families called cscA, cscB, cscC and cscD. Clusters encoding these cell-surface proteins were found only in complete genomes of Lactobacillus plantarum, Lactobacillus sakei, Enterococcus faecalis, Listeria innocua, Listeria monocytogenes, Lactococcus lactis ssp lactis and Bacillus cereus and in incomplete genomes of L. lactis ssp cremoris, Lactobacillus casei, Enterococcus faecium, Pediococcus pentosaceus, Lactobacillius brevis, Oenococcus oeni, Leuconostoc mesenteroides, and Bacillus thuringiensis. These genes are neither present in the genomes of streptococci, staphylococci and clostridia, nor in the Lactobacillus acidophilus group, suggesting a niche-specific distribution, possibly relating to association with plants. All encoded proteins have a signal peptide for secretion by the Sec-dependent pathway, while some have cell-surface anchors, novel WxL domains, and putative domains for sugar binding and degradation. Transcriptome analysis in L. plantarum shows that the cscA-D genes are co-expressed, supporting their operon organization. Many gene clusters are significantly up-regulated in a glucose-grown, ccpA-mutant derivative of L. plantarum, suggesting catabolite control. This is supported by the presence of predicted CRE-sites upstream or inside the up-regulated cscA-D gene clusters. Conclusion We propose that the CscA, CscB, CscC and Csc

Unveiling current Guanaco distribution in chile based upon niche structure of phylogeographic lineages: Andean puna to subpolar forests.

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González, Benito A; Samaniego, Horacio; Marín, Juan Carlos; Estades, Cristián F

2013-01-01

Niche description and differentiation at broad geographic scales have been recent major topics in ecology and evolution. Describing the environmental niche structure of sister taxa with known evolutionary trajectories stands out as a useful exercise in understanding niche requirements. Here we model the environmental niche structure and distribution of the recently resolved phylogeography of guanaco (Lama guanicoe) lineages on the western slope of the southern Andes. Using a maximum entropy framework, field data, and information on climate, topography, human density, and vegetation cover, we identify differences between the two subspecies (L.g.cacsilensis, L.g.guanicoe) and their intermediate-hybrid lineage, that most likely determine the distribution of this species. While aridity seems to be a major factor influencing the distribution at the species-level (annual precipitation ecological and/or evolutionary processes are shaping the niche of guanacos in Chile, producing discrepancies when comparing range distribution at the species-level (81,756 km(2)) with lineages-level (65,321 km(2)). The subspecies-specific description of niche structure is provided here based upon detailed spatial distribution of the lineages of guanacos in Chile. Such description provides a scientific tool to further develop large scale plans for habitat conservation and preservation of intraspecific genetic variability for this far ranging South American camelid, which inhabits a diversity of ecoregion types from Andean puna to subpolar forests.

Competition and niche separation of pelagic bacteria in freshwater habitats.

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Pernthaler, Jakob

2017-06-01

Freshwater bacterioplankton assemblages are composed of sympatric populations that can be delineated, for example, by ribosomal RNA gene relatedness and that differ in key ecophysiological properties. They may be free-living or attached, specialized for particular concentrations or subsets of substrates, or invest a variable amount of their resources in defence traits against protistan predators and viruses. Some may be motile and tactic whereas others are not, with far-reaching implications for their respective life styles and niche partitioning. The co-occurrence of competitors with overlapping growth requirements has profound consequences for the stability of community functions; it can to some extent be explained by habitat factors such as the microscale complexity and spatiotemporal variability of the lacustrine environments. On the other hand, the composition and diversity of freshwater microbial assemblages also reflects non-equilibrium states, dispersal and the stochasticity of community assembly processes. This review synoptically discusses the competition and niche separation of heterotrophic bacterial populations (defined at various levels of phylogenetic resolution) in the pelagic zone of inland surface waters from a variety of angles, focusing on habitat heterogeneity and the resulting biogeographic distribution patterns, the ecophysiological adaptations to the substrate field and the interactions of prokaryotes with predators and viruses. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Evolutionary constraints shape caste-specific gene expression across 15 ant species.

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Morandin, Claire; Mikheyev, Alexander S; Pedersen, Jes Søe; Helanterä, Heikki

2017-05-01

Development of polymorphic phenotypes from similar genomes requires gene expression differences. However, little is known about how morph-specific gene expression patterns vary on a broad phylogenetic scale. We hypothesize that evolution of morph-specific gene expression, and consequently morph-specific phenotypic evolution, may be constrained by gene essentiality and the amount of pleiotropic constraints. Here, we use comparative transcriptomics of queen and worker morphs, that is, castes, from 15 ant species to understand the constraints of morph-biased gene expression. In particular, we investigate how measures of evolutionary constraints at the sequence level (expression level, connectivity, and number of gene ontology [GO] terms) correlate with morph-biased expression. Our results show that genes indeed vary in their potential to become morph-biased. The existence of genes that are constrained in becoming caste-biased potentially limits the evolutionary decoupling of the caste phenotypes, that is, it might result in "caste load" occasioning from antagonistic fitness variation, similarly to sexually antagonistic fitness variation between males and females. On the other hand, we suggest that genes under low constraints are released from antagonistic variation and thus more likely to be co-opted for morph specific use. Overall, our results suggest that the factors that affect sequence evolutionary rates and evolution of plastic expression may largely overlap. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

New frontier in regenerative medicine: site-specific gene correction in patient-specific induced pluripotent stem cells.

Science.gov (United States)

Garate, Zita; Davis, Brian R; Quintana-Bustamante, Oscar; Segovia, Jose C

2013-06-01

Advances in cell and gene therapy are opening up new avenues for regenerative medicine. Because of their acquired pluripotency, human induced pluripotent stem cells (hiPSCs) are a promising source of autologous cells for regenerative medicine. They show unlimited self-renewal while retaining the ability, in principle, to differentiate into any cell type of the human body. Since Yamanaka and colleagues first reported the generation of hiPSCs in 2007, significant efforts have been made to understand the reprogramming process and to generate hiPSCs with potential for clinical use. On the other hand, the development of gene-editing platforms to increase homologous recombination efficiency, namely DNA nucleases (zinc finger nucleases, TAL effector nucleases, and meganucleases), is making the application of locus-specific gene therapy in human cells an achievable goal. The generation of patient-specific hiPSC, together with gene correction by homologous recombination, will potentially allow for their clinical application in the near future. In fact, reports have shown targeted gene correction through DNA-Nucleases in patient-specific hiPSCs. Various technologies have been described to reprogram patient cells and to correct these patient hiPSCs. However, no approach has been clearly more efficient and safer than the others. In addition, there are still significant challenges for the clinical application of these technologies, such as inefficient differentiation protocols, genetic instability resulting from the reprogramming process and hiPSC culture itself, the efficacy and specificity of the engineered DNA nucleases, and the overall homologous recombination efficiency. To summarize advances in the generation of gene corrected patient-specific hiPSCs, this review focuses on the available technological platforms, including their strengths and limitations regarding future therapeutic use of gene-corrected hiPSCs.

Cell type-specific suppression of mechanosensitive genes by audible sound stimulation.

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Kumeta, Masahiro; Takahashi, Daiji; Takeyasu, Kunio; Yoshimura, Shige H

2018-01-01

Audible sound is a ubiquitous environmental factor in nature that transmits oscillatory compressional pressure through the substances. To investigate the property of the sound as a mechanical stimulus for cells, an experimental system was set up using 94.0 dB sound which transmits approximately 10 mPa pressure to the cultured cells. Based on research on mechanotransduction and ultrasound effects on cells, gene responses to the audible sound stimulation were analyzed by varying several sound parameters: frequency, wave form, composition, and exposure time. Real-time quantitative PCR analyses revealed a distinct suppressive effect for several mechanosensitive and ultrasound-sensitive genes that were triggered by sounds. The effect was clearly observed in a wave form- and pressure level-specific manner, rather than the frequency, and persisted for several hours. At least two mechanisms are likely to be involved in this sound response: transcriptional control and RNA degradation. ST2 stromal cells and C2C12 myoblasts exhibited a robust response, whereas NIH3T3 cells were partially and NB2a neuroblastoma cells were completely insensitive, suggesting a cell type-specific response to sound. These findings reveal a cell-level systematic response to audible sound and uncover novel relationships between life and sound.

Spermatogenic Cell-Specific Gene Mutation in Mice via CRISPR-Cas9.

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Bai, Meizhu; Liang, Dan; Wang, Yinghua; Li, Qing; Wu, Yuxuan; Li, Jinsong

2016-05-20

Tissue-specific knockout technology enables the analysis of the gene function in specific tissues in adult mammals. However, conventional strategy for producing tissue-specific knockout mice is a time- and labor-consuming process, restricting rapid study of the gene function in vivo. CRISPR-Cas9 system from bacteria is a simple and efficient gene-editing technique, which has enabled rapid generation of gene knockout lines in mouse by direct injection of CRISPR-Cas9 into zygotes. Here, we demonstrate CRISPR-Cas9-mediated spermatogenic cell-specific disruption of Scp3 gene in testes in one step. We first generated transgenic mice by pronuclear injection of a plasmid containing Hspa2 promoter driving Cas9 expression and showed Cas9 specific expression in spermatogenic cells. We then produced transgenic mice carrying Hspa2 promoter driven Cas9 and constitutive expressed sgRNA targeting Scp3 gene. Male founders were infertile due to developmental arrest of spermatogenic cells while female founders could produce progeny normally. Consistently, male progeny from female founders were infertile and females could transmit the transgenes to the next generation. Our study establishes a CRISPR-Cas9-based one-step strategy to analyze the gene function in adult tissues by a temporal-spatial pattern. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

In a niche of time: do specialty hospitals outperform general services hospitals?

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Poole, LeJon; Davis, Jullet A; Gunby, Norris W

2013-01-01

Niche hospitals represent a growing segment in the health care industry. Niche facilities are primarily engaged in the treatment of cardiac or orthopedic conditions. The effectiveness of this strategy is of interest because niche hospitals focus on only the most profitable services. The purpose of this research was to assess the financial effectiveness of the niche strategy. We theorize that firm and market-level factors concomitantly with the strategy of the hospital-niche versus traditional-are associated with financial performance. This research used 2 data sources, the 2003 Medicare Cost Report and the 2003 Area Resource File. The sample was limited to only for-profit, urban, nongovernmental hospitals (n = 995). The data were analyzed using hierarchical least squares regression. Financial performance was operationalized using the hospital's return on assets. The principal finding of this project is that niche hospitals had significantly higher performance than traditional facilities. From the organizational perspective, the niche strategy leads to better financial performance. From a societal perspective, the niche strategy provides increased focus and efficiencies through repetition. Despite the limited focus of this strategy, patients who can access these providers may experience better outcomes than patients in more traditional hospitals.

Spontaneous Cognition and Epistemic Agency in the Cognitive Niche

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Fabry, Regina E.

2018-01-01

According to Thomas Metzinger, many human cognitive processes in the waking state are spontaneous and are deprived of the experience of epistemic agency. He considers mind wandering as a paradigm example of our recurring loss of epistemic agency. I will enrich this view by extending the scope of the concept of epistemic agency to include cases of depressive rumination and creative cognition, which are additional types of spontaneous cognition. Like mind wandering, they are characterized by unique phenomenal and functional properties that give rise to varying degrees of epistemic agency. The main claim of this paper will be that the experience of being an epistemic agent within a certain time frame is a relational phenomenon that emerges from the organism’s capacity to interact with its cognitive niche. To explore this relation, I develop a new framework that integrates phenomenological considerations on epistemic agency with a functional account of the reciprocal coupling of the embodied organism with its cognitive niche. This account rests upon dynamical accounts of strong embodied and embedded cognition and recent work on cognitive niche construction. Importantly, epistemic agency and organism-niche coupling are gradual phenomena ranging from weak to strong realizations. The emerging framework will be employed to analyze mind wandering, depressive rumination, and creative cognition as well as their commonalities and differences. Mind wandering and depressive rumination are cases of weak epistemic agency and organism-niche coupling. However, there are also important phenomenological, functional, and neuronal differences. In contrast, creative cognition is a case of strong epistemic agency and organism-niche coupling. By providing a phenomenological and functional analysis of these distinct types of spontaneous cognition, we can gain a better understanding of the importance of organism-niche interaction for the realization of epistemic agency.

Climatic niche conservatism and the evolutionary dynamics in species range boundaries

DEFF Research Database (Denmark)

Olalla-Tárraga1, Miguel Á.; McInnes, Linsey; Bini, Luis M.

2011-01-01

Aim Comparative evidence for phylogenetic niche conservatism – the tendency for lineages to retain their ancestral niches over long time scales – has so far been mixed, depending on spatial and taxonomic scale. We quantify and compare conservatism in the climatic factors defining range boundaries...... conservatism, as expected from their greater physiological sensitivity and lower dispersal abilities. Location Global; continental land masses excluding Antarctica. Methods We used nearly complete global distributional databases to estimate the climatic niche conservatism in extant continental mammals...... and amphibians. We characterized the climatic niche of each species by using a suite of variables and separately investigate conservatism in each variable using both taxonomic and phylogenetic approaches. Finally, we explored the spatial, taxonomic and phylogenetic patterns in recent climatic niche evolution...

Identification of the two rotavirus genes determining neutralization specificities

International Nuclear Information System (INIS)

Offit, P.A.; Blavat, G.

1986-01-01

Bovine rotavirus NCDV and simian rotavirus SA-11 represent two distinct rotavirus serotypes. A genetic approach was used to determine which viral gene segments segregated with serotype-specific viral neutralization. There were 16 reassortant rotarviruses derived by coinfection of MA-104 cells in vitro with the SA-11 and NCDV strains. The parental origin of reassortant rotavirus double-stranded RNA segments was determined by gene segment mobility in polyacrylamide gels and by hybridization with radioactively labeled parental viral transcripts. The authors found that two rotavirus gene segments found previously to code for outer capsid proteins vp3 and vp7 cosegreated with virus neutralization specificities

Identification of the two rotavirus genes determining neutralization specificities

Energy Technology Data Exchange (ETDEWEB)

Offit, P.A.; Blavat, G.

1986-01-01

Bovine rotavirus NCDV and simian rotavirus SA-11 represent two distinct rotavirus serotypes. A genetic approach was used to determine which viral gene segments segregated with serotype-specific viral neutralization. There were 16 reassortant rotarviruses derived by coinfection of MA-104 cells in vitro with the SA-11 and NCDV strains. The parental origin of reassortant rotavirus double-stranded RNA segments was determined by gene segment mobility in polyacrylamide gels and by hybridization with radioactively labeled parental viral transcripts. The authors found that two rotavirus gene segments found previously to code for outer capsid proteins vp3 and vp7 cosegreated with virus neutralization specificities.

Transcriptional Profiling Identifies Location-Specific and Breed-Specific Differentially Expressed Genes in Embryonic Myogenesis in Anas Platyrhynchos.

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Rong-Ping Zhang

Full Text Available Skeletal muscle growth and development are highly orchestrated processes involving significant changes in gene expressions. Differences in the location-specific and breed-specific genes and pathways involved have important implications for meat productions and meat quality. Here, RNA-Seq was performed to identify differences in the muscle deposition between two muscle locations and two duck breeds for functional genomics studies. To achieve those goals, skeletal muscle samples were collected from the leg muscle (LM and the pectoral muscle (PM of two genetically different duck breeds, Heiwu duck (H and Peking duck (P, at embryonic 15 days. Functional genomics studies were performed in two experiments: Experiment 1 directly compared the location-specific genes between PM and LM, and Experiment 2 compared the two breeds (H and P at the same developmental stage (embryonic 15 days. Almost 13 million clean reads were generated using Illumina technology (Novogene, Beijing, China on each library, and more than 70% of the reads mapped to the Peking duck (Anas platyrhynchos genome. A total of 168 genes were differentially expressed between the two locations analyzed in Experiment 1, whereas only 8 genes were differentially expressed when comparing the same location between two breeds in Experiment 2. Gene Ontology (GO and the Kyoto Encyclopedia of Genes and Genomes pathways (KEGG were used to functionally annotate DEGs (differentially expression genes. The DEGs identified in Experiment 1 were mainly involved in focal adhesion, the PI3K-Akt signaling pathway and ECM-receptor interaction pathways (corrected P-value<0.05. In Experiment 2, the DEGs were associated with only the ribosome signaling pathway (corrected P-value<0.05. In addition, quantitative real-time PCR was used to confirm 15 of the differentially expressed genes originally detected by RNA-Seq. A comparative transcript analysis of the leg and pectoral muscles of two duck breeds not only

Geographical parthenogenesis: General purpose genotypes and frozen niche variation

DEFF Research Database (Denmark)

Vrijenhoek, Robert C.; Parker, Dave

2009-01-01

hypotheses concerning the evolution of niche breadth in asexual species - the "general-purpose genotype" (GPG) and "frozen niche-variation" (FNV) models. The two models are often portrayed as mutually exclusive, respectively viewing clonal lineages as generalists versus specialists. Nonetheless...

A family business: stem cell progeny join the niche to regulate homeostasis.

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Hsu, Ya-Chieh; Fuchs, Elaine

2012-01-23

Stem cell niches, the discrete microenvironments in which the stem cells reside, play a dominant part in regulating stem cell activity and behaviours. Recent studies suggest that committed stem cell progeny become indispensable components of the niche in a wide range of stem cell systems. These unexpected niche inhabitants provide versatile feedback signals to their stem cell parents. Together with other heterologous cell types that constitute the niche, they contribute to the dynamics of the microenvironment. As progeny are often located in close proximity to stem cell niches, similar feedback regulations may be the underlying principles shared by different stem cell systems.

A niche marketing guide for lamb cooperatives

OpenAIRE

Kazmierczak, Tamra Kirkpatrick; Bell, James B.

1995-01-01

The two types of niche markets targeted by lamb marketing cooperatives are described in this guide. The first type includes specialty middlemen outlets that cooperatives used to market lamb to specialized niches within the traditional meat marketing system of retail food stores, restaurants, food service outlets, and specialty distributors. The second type includes those outlets that cooperatives used to market lamb directly to the consumer, such as freezer markets, farmers' markets, mobile m...

The Drosophila Translational Control Element (TCE is required for high-level transcription of many genes that are specifically expressed in testes.

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Rebeccah J Katzenberger

Full Text Available To investigate the importance of core promoter elements for tissue-specific transcription of RNA polymerase II genes, we examined testis-specific transcription in Drosophila melanogaster. Bioinformatic analyses of core promoter sequences from 190 genes that are specifically expressed in testes identified a 10 bp A/T-rich motif that is identical to the translational control element (TCE. The TCE functions in the 5' untranslated region of Mst(3CGP mRNAs to repress translation, and it also functions in a heterologous gene to regulate transcription. We found that among genes with focused initiation patterns, the TCE is significantly enriched in core promoters of genes that are specifically expressed in testes but not in core promoters of genes that are specifically expressed in other tissues. The TCE is variably located in core promoters and is conserved in melanogaster subgroup species, but conservation dramatically drops in more distant species. In transgenic flies, short (300-400 bp genomic regions containing a TCE directed testis-specific transcription of a reporter gene. Mutation of the TCE significantly reduced but did not abolish reporter gene transcription indicating that the TCE is important but not essential for transcription activation. Finally, mutation of testis-specific TFIID (tTFIID subunits significantly reduced the transcription of a subset of endogenous TCE-containing but not TCE-lacking genes, suggesting that tTFIID activity is limited to TCE-containing genes but that tTFIID is not an obligatory regulator of TCE-containing genes. Thus, the TCE is a core promoter element in a subset of genes that are specifically expressed in testes. Furthermore, the TCE regulates transcription in the context of short genomic regions, from variable locations in the core promoter, and both dependently and independently of tTFIID. These findings set the stage for determining the mechanism by which the TCE regulates testis-specific transcription and

The Drosophila Translational Control Element (TCE) is required for high-level transcription of many genes that are specifically expressed in testes.

Science.gov (United States)

Katzenberger, Rebeccah J; Rach, Elizabeth A; Anderson, Ashley K; Ohler, Uwe; Wassarman, David A

2012-01-01

To investigate the importance of core promoter elements for tissue-specific transcription of RNA polymerase II genes, we examined testis-specific transcription in Drosophila melanogaster. Bioinformatic analyses of core promoter sequences from 190 genes that are specifically expressed in testes identified a 10 bp A/T-rich motif that is identical to the translational control element (TCE). The TCE functions in the 5' untranslated region of Mst(3)CGP mRNAs to repress translation, and it also functions in a heterologous gene to regulate transcription. We found that among genes with focused initiation patterns, the TCE is significantly enriched in core promoters of genes that are specifically expressed in testes but not in core promoters of genes that are specifically expressed in other tissues. The TCE is variably located in core promoters and is conserved in melanogaster subgroup species, but conservation dramatically drops in more distant species. In transgenic flies, short (300-400 bp) genomic regions containing a TCE directed testis-specific transcription of a reporter gene. Mutation of the TCE significantly reduced but did not abolish reporter gene transcription indicating that the TCE is important but not essential for transcription activation. Finally, mutation of testis-specific TFIID (tTFIID) subunits significantly reduced the transcription of a subset of endogenous TCE-containing but not TCE-lacking genes, suggesting that tTFIID activity is limited to TCE-containing genes but that tTFIID is not an obligatory regulator of TCE-containing genes. Thus, the TCE is a core promoter element in a subset of genes that are specifically expressed in testes. Furthermore, the TCE regulates transcription in the context of short genomic regions, from variable locations in the core promoter, and both dependently and independently of tTFIID. These findings set the stage for determining the mechanism by which the TCE regulates testis-specific transcription and understanding the

Compatible ecological niche signals between biological and archaeological datasets for late-surviving Neandertals.

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Bible, Rachael C; Peterson, A Townsend

2018-04-17

To assess ecological niche similarity for biological and archaeological samples representing late-surviving Neandertals in Europe to evaluate the validity of combining these two types of data in ecological niche modeling analyses. Tests of niche conservatism were used to assess niche similarity and niche identity of samples of morphologically diagnostic Neandertal remains and Middle Paleolithic (MP) archaeological sites dating to the time period leading up to Neandertal extinction. Paleoenvironmental reconstructions for the Pre-H4 (43.3-40.2 ky cal BP) were used as environmental space analyses. Null hypotheses of niche similarity and identity of the two types of samples could not be rejected. As primary and secondary evidence of Neandertal occurrence during the Pre-H4 show high levels of niche similarity and identity, combining the two types of occurrence data to create larger samples for niche analyses is justified without the concern that different environmental signals could complicate future research. © 2018 Wiley Periodicals, Inc.

Insights from ecological niche modeling on the taxonomic distinction and niche differentiation between the black-spotted and red-spotted tokay geckoes (Gekko gecko).

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Zhang, Yueyun; Chen, Chongtao; Li, Li; Zhao, Chengjian; Chen, Weicai; Huang, Yong

2014-09-01

The black-spotted tokay and the red-spotted tokay are morphologically distinct and have largely allopatric distributions. The black-spotted tokay is characterized by a small body size and dark skin with sundry spots, while the red-spotted tokay has a relatively large body size and red spots. Based on morphological, karyotypic, genetic, and distribution differences, recent studies suggested their species status; however, their classifications remain controversial, and additional data such as ecological niches are necessary to establish firm hypotheses regarding their taxonomic status. We reconstructed their ecological niches models using climatic and geographic data. We then performed niche similarity tests (niche identity and background tests) and point-based analyses to explore whether ecological differentiation has occurred, and whether such differences are sufficient to explain the maintenance of their separate segments of environmental ranges. We found that both niche models of the black- and the red-spotted tokay had a good fit and a robust performance, as indicated by the high area under the curve (AUC) values ("black" = 0.982, SD = ± 0.002, "red" = 0.966 ± 0.02). Significant ecological differentiation across the entire geographic range was found, indicating that the involvement of ecological differentiation is important for species differentiation. Divergence along the environmental axes is highly associated with climatic conditions, with isothermality being important for the "black" form, while temperature seasonality, precipitation of warmest quarter, and annual temperature range together being important for the "red" form. These factors are likely important factors in niche differentiation between the two forms, which result in morphological replacement. Overall, beside morphological and genetic differentiation information, our results contribute to additional insights into taxonomic distinction and niche differentiation between the black- and the red

Study on Fusion Protein and Its gene in Baculovirus Specificity

International Nuclear Information System (INIS)

Nemr, W.A.H.

2012-01-01

Baculoviruses are subdivided into two groups depending on the type of budded virus envelop fusion protein; group I utilized gp64 which include the most of nucleopolyhedroviruses (NPVs), group II utilized F protein which include the remnants of NPVs and all Granuloviruses (GVs). Recent studies reported the viral F protein coding gene as a host cellular sourced gene and may evolutionary acquired from the host genome referring to phylogeny analysis of fusion proteins. Thus, it was deduced that F protein coding gene is species- specific nucleotide sequence related to the type of the specific host and if virus could infect an unexpected host, the resulted virus may encode a vary F gene. In this regard, the present study utilized the mentioned properties of F gene in an attempt to produce a model of specific and more economic wider range granulovirus bio- pesticide able to infect both Spodoptera littoralis and Phthorimaea operculella larvae. Multiple sequence alignment and phylogeny analysis were performed on six members of group II baculovirus, novel universal PCR primers were manually designed from the conserved regions in the alignment graph, targeted to amplify species- specific sequence entire F gene open reading frame (ORF) which is useful in molecular identification of baculovirus in unknown samples. So, the PCR product of SpliGV used to prepare a specific probe for the F gene of this type of virus. Results reflected that it is possible to infect S. littoralis larvae by PhopGV if injected into larval haemocoel, the resulted virus of this infection showed by using DNA hybridization technique to be encode to F gene homologous with the F gene of Spli GV, which is revealed that the resulted virus acquired this F gene sequence from the host genome after infection. Consequently, these results may infer that if genetic aberrations occur in the host genome, this may affect in baculoviral infectivity. So, this study aimed to investigate the effect of gamma radiation at

Behavioural manipulation of insect hosts by Baculoviridae as a process of niche construction.

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Hamblin, Steven; Tanaka, Mark M

2013-08-16

Niche construction has received increasing attention in recent years as a vital force in evolution and examples of niche construction have been identified in a wide variety of taxa, but viruses are conspicuously absent. In this study we explore how niche construction can lead to viruses engineering their hosts (including behavioural manipulation) with feedback on selective pressures for viral transmission and virulence. To illustrate this concept we focus on Baculoviridae, a family of invertebrate viruses that have evolved to modify the feeding behaviour of their lepidopteran hosts and liquefy their cadavers as part of the course of infection. We present a mathematical model showing how niche construction leads to feedback from the behavioural manipulation to the liquefaction of the host, linking the evolution of both of these traits, and show how this association arises from the action of niche construction. Model results show that niche construction is plausible in this system and delineates the conditions under which niche construction will occur. Niche construction in this system is also shown to be sensitive to parameter values that reflect ecological forces. Our model demonstrates that niche construction can be a potent force in viral evolution and can lead to the acquisition and maintenance of the behavioural manipulation and liquefaction traits in Baculoviridae via the niche constructing effects on the host. These results show the potential for niche construction theory to provide new insights into viral evolution.

Constellation Map: Downstream visualization and interpretation of gene set enrichment results [version 1; referees: 2 approved

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Yan Tan

2015-06-01

Full Text Available Summary: Gene set enrichment analysis (GSEA approaches are widely used to identify coordinately regulated genes associated with phenotypes of interest. Here, we present Constellation Map, a tool to visualize and interpret the results when enrichment analyses yield a long list of significantly enriched gene sets. Constellation Map identifies commonalities that explain the enrichment of multiple top-scoring gene sets and maps the relationships between them. Constellation Map can help investigators take full advantage of GSEA and facilitates the biological interpretation of enrichment results. Availability: Constellation Map is freely available as a GenePattern module at http://www.genepattern.org.

Microhabitat and Climatic Niche Change Explain Patterns of Diversification among Frog Families.

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Moen, Daniel S; Wiens, John J

2017-07-01

A major goal of ecology and evolutionary biology is to explain patterns of species richness among clades. Differences in rates of net diversification (speciation minus extinction over time) may often explain these patterns, but the factors that drive variation in diversification rates remain uncertain. Three important candidates are climatic niche position (e.g., whether clades are primarily temperate or tropical), rates of climatic niche change among species within clades, and microhabitat (e.g., aquatic, terrestrial, arboreal). The first two factors have been tested separately in several studies, but the relative importance of all three is largely unknown. Here we explore the correlates of diversification among families of frogs, which collectively represent ∼88% of amphibian species. We assemble and analyze data on phylogeny, climate, and microhabitat for thousands of species. We find that the best-fitting phylogenetic multiple regression model includes all three types of variables: microhabitat, rates of climatic niche change, and climatic niche position. This model explains 67% of the variation in diversification rates among frog families, with arboreal microhabitat explaining ∼31%, niche rates ∼25%, and climatic niche position ∼11%. Surprisingly, we show that microhabitat can have a much stronger influence on diversification than climatic niche position or rates of climatic niche change.

Regulatory System for Stem/Progenitor Cell Niches in the Adult Rodent Pituitary

Science.gov (United States)

Yoshida, Saishu; Kato, Takako; Kato, Yukio

2016-01-01

The anterior lobe of the pituitary gland is a master endocrine tissue composed of five types of endocrine cells. Although the turnover rate of pituitary endocrine cells is as low as about 1.6% per day, recent studies have demonstrated that Sex-determining region Y-box 2 (SOX2)+-cells exist as pituitary stem/progenitor cells in the adult anterior lobe and contribute to cell regeneration. Notably, SOX2+-pituitary stem/progenitor cells form two types of niches in this tissue: the marginal cell layer (MCL-niche) and the dense cell clusters scattering in the parenchyma (parenchymal-niche). However, little is known about the mechanisms and factors for regulating the pituitary stem/progenitor cell niches, as well as the functional differences between the two types of niches. Elucidation of the regulatory mechanisms in the niches might enable us to understand the cell regeneration system that acts in accordance with physiological demands in the adult pituitary. In this review, so as to reveal the regulatory mechanisms of the two types of niche, we summarize the regulatory factors and their roles in the adult rodent pituitary niches by focusing on three components: soluble factors, cell surface proteins and extracellular matrixes. PMID:26761002

Regulatory System for Stem/Progenitor Cell Niches in the Adult Rodent Pituitary

Directory of Open Access Journals (Sweden)

Saishu Yoshida

2016-01-01

Full Text Available The anterior lobe of the pituitary gland is a master endocrine tissue composed of five types of endocrine cells. Although the turnover rate of pituitary endocrine cells is as low as about 1.6% per day, recent studies have demonstrated that Sex-determining region Y-box 2 (SOX2+-cells exist as pituitary stem/progenitor cells in the adult anterior lobe and contribute to cell regeneration. Notably, SOX2+-pituitary stem/progenitor cells form two types of niches in this tissue: the marginal cell layer (MCL-niche and the dense cell clusters scattering in the parenchyma (parenchymal-niche. However, little is known about the mechanisms and factors for regulating the pituitary stem/progenitor cell niches, as well as the functional differences between the two types of niches. Elucidation of the regulatory mechanisms in the niches might enable us to understand the cell regeneration system that acts in accordance with physiological demands in the adult pituitary. In this review, so as to reveal the regulatory mechanisms of the two types of niche, we summarize the regulatory factors and their roles in the adult rodent pituitary niches by focusing on three components: soluble factors, cell surface proteins and extracellular matrixes.

The making of an immigrant niche.

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Waldinger, R

1994-01-01

"This article speaks to the conceptual and methodological issues in research on the making of an immigrant niche through a case study of immigrant professionals in New York City government." The author argues that "the growth of this immigrant niche resulted from changes in the relative supply of native workers and in the structure of employment, which opened the bureaucracy to immigrants and reduced native/immigrant competition. These shifts opened hiring portals; given the advantages of network hiring for workers and managers, and an immigrant propensity for government employment, network recruitment led to a rapid buildup in immigrant ranks." excerpt

Tissue-specifically regulated site-specific excision of selectable marker genes in bivalent insecticidal, genetically-modified rice.

Science.gov (United States)

Hu, Zhan; Ding, Xuezhi; Hu, Shengbiao; Sun, Yunjun; Xia, Liqiu

2013-12-01

Marker-free, genetically-modified rice was created by the tissue-specifically regulated Cre/loxP system, in which the Cre recombinase gene and hygromycin phosphotransferase gene (hpt) were flanked by two directly oriented loxP sites. Cre expression was activated by the tissue-specific promoter OsMADS45 in flower or napin in seed, resulting in simultaneous excision of the recombinase and marker genes. Segregation of T1 progeny was performed to select recombined plants. The excision was confirmed by PCR, Southern blot and sequence analyses indicating that efficiency varied from 10 to 53 % for OsMADS45 and from 12 to 36 % for napin. The expression of cry1Ac and vip3A was detected by RT-PCR analysis in marker-free transgenic rice. These results suggested that our tissue-specifically regulated Cre/loxP system could auto-excise marker genes from transgenic rice and alleviate public concerns about the security of GM crops.

Maturation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in 3D collagen matrix: Effects of niche cell supplementation and mechanical stimulation.

Science.gov (United States)

Zhang, W; Kong, C W; Tong, M H; Chooi, W H; Huang, N; Li, R A; Chan, B P

2017-02-01

. Specifically, with 3% niche cells including both fibroblasts and mesenchymal stem cells, a more mature hESC-CMs derived cardiac strip was resulted, in terms of compaction and spreading of cells, and upregulation of molecular signature in both gene and protein expression of maturation. Mechanical loading, particularly cyclic stretch, produces engineered cardiac tissues with higher maturity in terms of molecular signature markers and functional parameters including twitch force, elastic modulus and sarcomere length, when comparing with static stretch or non-stretched controls. The current study demonstrates that the application of niche cells and mechanical stretch both stimulate the maturation of hESC-CMs in 3D architecture, resulting in more mature cardiac strips. Our results contribute to bioengineering of functional heart tissue strips for drug screening and disease modeling. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Genetic Basis for Developmental Homeostasis of Germline Stem Cell Niche Number: A Network of Tramtrack-Group Nuclear BTB Factors

Science.gov (United States)

Chalvet, Fabienne; Netter, Sophie; Dos Santos, Nicolas; Poisot, Emilie; Paces-Fessy, Mélanie; Cumenal, Delphine; Peronnet, Frédérique; Pret, Anne-Marie; Théodore, Laurent

2012-01-01

The potential to produce new cells during adult life depends on the number of stem cell niches and the capacity of stem cells to divide, and is therefore under the control of programs ensuring developmental homeostasis. However, it remains generally unknown how the number of stem cell niches is controlled. In the insect ovary, each germline stem cell (GSC) niche is embedded in a functional unit called an ovariole. The number of ovarioles, and thus the number of GSC niches, varies widely among species. In Drosophila, morphogenesis of ovarioles starts in larvae with the formation of terminal filaments (TFs), each made of 8–10 cells that pile up and sort in stacks. TFs constitute organizers of individual germline stem cell niches during larval and early pupal development. In the Drosophila melanogaster subgroup, the number of ovarioles varies interspecifically from 8 to 20. Here we show that pipsqueak, Trithorax-like, batman and the bric-à-brac (bab) locus, all encoding nuclear BTB/POZ factors of the Tramtrack Group, are involved in limiting the number of ovarioles in D. melanogaster. At least two different processes are differentially perturbed by reducing the function of these genes. We found that when the bab dose is reduced, sorting of TF cells into TFs was affected such that each TF contains fewer cells and more TFs are formed. In contrast, psq mutants exhibited a greater number of TF cells per ovary, with a normal number of cells per TF, thereby leading to formation of more TFs per ovary than in the wild type. Our results indicate that two parallel genetic pathways under the control of a network of nuclear BTB factors are combined in order to negatively control the number of germline stem cell niches. PMID:23185495

Performance of single and concatenated sets of mitochondrial genes at inferring metazoan relationships relative to full mitogenome data.

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Justin C Havird

Full Text Available Mitochondrial (mt genes are some of the most popular and widely-utilized genetic loci in phylogenetic studies of metazoan taxa. However, their linked nature has raised questions on whether using the entire mitogenome for phylogenetics is overkill (at best or pseudoreplication (at worst. Moreover, no studies have addressed the comparative phylogenetic utility of mitochondrial genes across individual lineages within the entire Metazoa. To comment on the phylogenetic utility of individual mt genes as well as concatenated subsets of genes, we analyzed mitogenomic data from 1865 metazoan taxa in 372 separate lineages spanning genera to subphyla. Specifically, phylogenies inferred from these datasets were statistically compared to ones generated from all 13 mt protein-coding (PC genes (i.e., the "supergene" set to determine which single genes performed "best" at, and the minimum number of genes required to, recover the "supergene" topology. Surprisingly, the popular marker COX1 performed poorest, while ND5, ND4, and ND2 were most likely to reproduce the "supergene" topology. Averaged across all lineages, the longest ∼2 mt PC genes were sufficient to recreate the "supergene" topology, although this average increased to ∼5 genes for datasets with 40 or more taxa. Furthermore, concatenation of the three "best" performing mt PC genes outperformed that of the three longest mt PC genes (i.e, ND5, COX1, and ND4. Taken together, while not all mt PC genes are equally interchangeable in phylogenetic studies of the metazoans, some subset can serve as a proxy for the 13 mt PC genes. However, the exact number and identity of these genes is specific to the lineage in question and cannot be applied indiscriminately across the Metazoa.

Niche partitioning of feeding microhabitats produces a unique function for herbivorous rabbitfishes (Perciformes, Siganidae) on coral reefs

Science.gov (United States)

Fox, R. J.; Bellwood, D. R.

2013-03-01

Niche theory predicts that coexisting species minimise competition by evolving morphological or behavioural specialisations that allow them to spread out along resource axes such as space, diet and temporal activity. These specialisations define how a species interacts with its environment and, by extension, determine its functional role. Here, we examine the feeding niche of three species of coral reef-dwelling rabbitfishes (Siganidae, Siganus). By comparing aspects of their feeding behaviour (bite location, bite rate, foraging distance) with that of representative species from two other abundant herbivorous fish families, the parrotfishes (Labridae, Scarus) and surgeonfishes (Acanthuridae, Acanthurus), we examine whether rabbitfishes have a feeding niche distinct from other members of the herbivore guild. Measurements of the penetration of the fishes' snouts and bodies into reef concavities when feeding revealed that rabbitfish fed to a greater degree from reef crevices and interstices than other herbivores. There was just a 40 % overlap in the penetration-depth niche between rabbitfish and surgeonfish and a 45 % overlap between rabbitfish and parrotfish, compared with the almost complete niche overlap (95 %) recorded for parrotfish and surgeonfish along this spatial niche axis. Aspects of the morphology of rabbitfish which may contribute to this niche segregation include a comparatively longer, narrower snout and narrower head. Our results suggest that sympatric coexistence of rabbitfish and other reef herbivores is facilitated by segregation along a spatial (and potentially dietary) axis. This segregation results in a unique functional role for rabbitfishes among roving herbivores that of "crevice-browser": a group that specifically feeds on crevice-dwelling algal or benthic organisms. This functional trait may have implications for reef ecosystem processes in terms of controlling the successional development of crevice-based algal communities, reducing their

MO-DE-207B-03: Improved Cancer Classification Using Patient-Specific Biological Pathway Information Via Gene Expression Data

Energy Technology Data Exchange (ETDEWEB)

Young, M; Craft, D [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)

2016-06-15

Purpose: To develop an efficient, pathway-based classification system using network biology statistics to assist in patient-specific response predictions to radiation and drug therapies across multiple cancer types. Methods: We developed PICS (Pathway Informed Classification System), a novel two-step cancer classification algorithm. In PICS, a matrix m of mRNA expression values for a patient cohort is collapsed into a matrix p of biological pathways. The entries of p, which we term pathway scores, are obtained from either principal component analysis (PCA), normal tissue centroid (NTC), or gene expression deviation (GED). The pathway score matrix is clustered using both k-means and hierarchical clustering, and a clustering is judged by how well it groups patients into distinct survival classes. The most effective pathway scoring/clustering combination, per clustering p-value, thus generates various ‘signatures’ for conventional and functional cancer classification. Results: PICS successfully regularized large dimension gene data, separated normal and cancerous tissues, and clustered a large patient cohort spanning six cancer types. Furthermore, PICS clustered patient cohorts into distinct, statistically-significant survival groups. For a suboptimally-debulked ovarian cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00127) showed significant improvement over that of a prior gene expression-classified study (p = .0179). For a pancreatic cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00141) showed significant improvement over that of a prior gene expression-classified study (p = .04). Pathway-based classification confirmed biomarkers for the pyrimidine, WNT-signaling, glycerophosphoglycerol, beta-alanine, and panthothenic acid pathways for ovarian cancer. Despite its robust nature, PICS requires significantly less run time than current pathway scoring methods. Conclusion: This work validates the PICS method to improve

Neural Crossroads in the Hematopoietic Stem Cell Niche.

Science.gov (United States)

Agarwala, Sobhika; Tamplin, Owen J

2018-05-29

The hematopoietic stem cell (HSC) niche supports steady-state hematopoiesis and responds to changing needs during stress and disease. The nervous system is an important regulator of the niche, and its influence is established early in development when stem cells are specified. Most research has focused on direct innervation of the niche, however recent findings show there are different modes of neural control, including globally by the central nervous system (CNS) and hormone release, locally by neural crest-derived mesenchymal stem cells, and intrinsically by hematopoietic cells that express neural receptors and neurotransmitters. Dysregulation between neural and hematopoietic systems can contribute to disease, however new therapeutic opportunities may be found among neuroregulator drugs repurposed to support hematopoiesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Profiling of gene duplication patterns of sequenced teleost genomes: evidence for rapid lineage-specific genome expansion mediated by recent tandem duplications.

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Lu, Jianguo; Peatman, Eric; Tang, Haibao; Lewis, Joshua; Liu, Zhanjiang

2012-06-15

Gene duplication has had a major impact on genome evolution. Localized (or tandem) duplication resulting from unequal crossing over and whole genome duplication are believed to be the two dominant mechanisms contributing to vertebrate genome evolution. While much scrutiny has been directed toward discerning patterns indicative of whole-genome duplication events in teleost species, less attention has been paid to the continuous nature of gene duplications and their impact on the size, gene content, functional diversity, and overall architecture of teleost genomes. Here, using a Markov clustering algorithm directed approach we catalogue and analyze patterns of gene duplication in the four model teleost species with chromosomal coordinates: zebrafish, medaka, stickleback, and Tetraodon. Our analyses based on set size, duplication type, synonymous substitution rate (Ks), and gene ontology emphasize shared and lineage-specific patterns of genome evolution via gene duplication. Most strikingly, our analyses highlight the extraordinary duplication and retention rate of recent duplicates in zebrafish and their likely role in the structural and functional expansion of the zebrafish genome. We find that the zebrafish genome is remarkable in its large number of duplicated genes, small duplicate set size, biased Ks distribution toward minimal mutational divergence, and proportion of tandem and intra-chromosomal duplicates when compared with the other teleost model genomes. The observed gene duplication patterns have played significant roles in shaping the architecture of teleost genomes and appear to have contributed to the recent functional diversification and divergence of important physiological processes in zebrafish. We have analyzed gene duplication patterns and duplication types among the available teleost genomes and found that a large number of genes were tandemly and intrachromosomally duplicated, suggesting their origin of independent and continuous duplication

Highly specific expression of luciferase gene in lungs of naive nude mice directed by prostate-specific antigen promoter

International Nuclear Information System (INIS)

Li Hongwei; Li Jinzhong; Helm, Gregory A.; Pan Dongfeng

2005-01-01

PSA promoter has been demonstrated the utility for tissue-specific toxic gene therapy in prostate cancer models. Characterization of foreign gene overexpression in normal animals elicited by PSA promoter should help evaluate therapy safety. Here we constructed an adenovirus vector (AdPSA-Luc), containing firefly luciferase gene under the control of the 5837 bp long prostate-specific antigen promoter. A charge coupled device video camera was used to non-invasively image expression of firefly luciferase in nude mice on days 3, 7, 11 after injection of 2 x 10 9 PFU of AdPSA-Luc virus via tail vein. The result showed highly specific expression of the luciferase gene in lungs of mice from day 7. The finding indicates the potential limitations of the suicide gene therapy of prostate cancer based on selectivity of PSA promoter. By contrary, it has encouraging implications for further development of vectors via PSA promoter to enable gene therapy for pulmonary diseases

c-Kit-mediated functional positioning of stem cells to their niches is essential for maintenance and regeneration of adult hematopoiesis.

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Yuki Kimura

Full Text Available The mechanism by which hematopoietic stem and progenitor cells (HSPCs through interaction with their niches maintain and reconstitute adult hematopoietic cells is unknown. To functionally and genetically track localization of HSPCs with their niches, we employed novel mutant loxPs, lox66 and lox71 and Cre-recombinase technology to conditionally delete c-Kit in adult mice, while simultaneously enabling GFP expression in the c-Kit-deficient cells. Conditional deletion of c-Kit resulted in hematopoietic failure and splenic atrophy both at steady state and after marrow ablation leading to the demise of the treated adult mice. Within the marrow, the c-Kit-expressing GFP(+ cells were positioned to Kit ligand (KL-expressing niche cells. This c-Kit-mediated cellular adhesion was essential for long-term maintenance and expansion of HSPCs. These results lay the foundation for delivering KL within specific niches to maintain and restore hematopoiesis.

Identification of a novel set of genes reflecting different in vivo invasive patterns of human GBM cells

International Nuclear Information System (INIS)

Monticone, Massimiliano; Giaretti, Walter; Pfeffer, Ulrich; Daga, Antonio; Candiani, Simona; Romeo, Francesco; Mirisola, Valentina; Viaggi, Silvia; Melloni, Ilaria; Pedemonte, Simona; Zona, Gianluigi

2012-01-01

Most patients affected by Glioblastoma multiforme (GBM, grade IV glioma) experience a recurrence of the disease because of the spreading of tumor cells beyond surgical boundaries. Unveiling mechanisms causing this process is a logic goal to impair the killing capacity of GBM cells by molecular targeting. We noticed that our long-term GBM cultures, established from different patients, may display two categories/types of growth behavior in an orthotopic xenograft model: expansion of the tumor mass and formation of tumor branches/nodules (nodular like, NL-type) or highly diffuse single tumor cell infiltration (HD-type). We determined by DNA microarrays the gene expression profiles of three NL-type and three HD-type long-term GBM cultures. Subsequently, individual genes with different expression levels between the two groups were identified using Significance Analysis of Microarrays (SAM). Real time RT-PCR, immunofluorescence and immunoblot analyses, were performed for a selected subgroup of regulated gene products to confirm the results obtained by the expression analysis. Here, we report the identification of a set of 34 differentially expressed genes in the two types of GBM cultures. Twenty-three of these genes encode for proteins localized to the plasma membrane and 9 of these for proteins are involved in the process of cell adhesion. This study suggests the participation in the diffuse infiltrative/invasive process of GBM cells within the CNS of a novel set of genes coding for membrane-associated proteins, which should be thus susceptible to an inhibition strategy by specific targeting. Massimiliano Monticone and Antonio Daga contributed equally to this work

Identification of a novel set of genes reflecting different in vivo invasive patterns of human GBM cells.

Science.gov (United States)

Monticone, Massimiliano; Daga, Antonio; Candiani, Simona; Romeo, Francesco; Mirisola, Valentina; Viaggi, Silvia; Melloni, Ilaria; Pedemonte, Simona; Zona, Gianluigi; Giaretti, Walter; Pfeffer, Ulrich; Castagnola, Patrizio

2012-08-17

Most patients affected by Glioblastoma multiforme (GBM, grade IV glioma) experience a recurrence of the disease because of the spreading of tumor cells beyond surgical boundaries. Unveiling mechanisms causing this process is a logic goal to impair the killing capacity of GBM cells by molecular targeting.We noticed that our long-term GBM cultures, established from different patients, may display two categories/types of growth behavior in an orthotopic xenograft model: expansion of the tumor mass and formation of tumor branches/nodules (nodular like, NL-type) or highly diffuse single tumor cell infiltration (HD-type). We determined by DNA microarrays the gene expression profiles of three NL-type and three HD-type long-term GBM cultures. Subsequently, individual genes with different expression levels between the two groups were identified using Significance Analysis of Microarrays (SAM). Real time RT-PCR, immunofluorescence and immunoblot analyses, were performed for a selected subgroup of regulated gene products to confirm the results obtained by the expression analysis. Here, we report the identification of a set of 34 differentially expressed genes in the two types of GBM cultures. Twenty-three of these genes encode for proteins localized to the plasma membrane and 9 of these for proteins are involved in the process of cell adhesion. This study suggests the participation in the diffuse infiltrative/invasive process of GBM cells within the CNS of a novel set of genes coding for membrane-associated proteins, which should be thus susceptible to an inhibition strategy by specific targeting.Massimiliano Monticone and Antonio Daga contributed equally to this work.

The Vascular Niche in Tissue Repair: A Therapeutic Target for Regeneration

OpenAIRE

Rivera, Francisco J.; Silva, Maria Elena; Aigner, Ludwig

2017-01-01

Editorial on the Research Topic The Vascular Niche in Tissue Repair: A Therapeutic Target for Regeneration In mammals, although regeneration is quite restricted to a number of tissues and organs, this particular healing process is possible through the existence of tissue-resident stem/progenitor cells. Upon injury, these cells are activated, they proliferate, migrate, and differentiate into tissue-specific cells and functionally replace the damaged or lost cells. Besides this, angio...

Major gene mutations and domestication of plants

International Nuclear Information System (INIS)

Ashri, A.

1989-01-01

From the approximately 200,000 species of flowering plants known, only about 200 have been domesticated. The process has taken place in many regions over long periods. At present there is great interest in domesticating new species and developing new uses for existing ones in order to supply needed food, industrial raw materials, etc. It is proposed that major gene mutations were important in domestication; many key characters distinguishing cultivated from related wild species are controlled by one or very few major genes. The deliberate effort to domesticate new species requires at least the following: identification of needs and potential sources, establishment of suitable niches, choice of taxa to be domesticated, specification of the desired traits and key characters to be modified, as well as the potential role of induced mutations. (author). 14 refs

Allele specific expression in worker reproduction genes in the bumblebee Bombus terrestris

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Harindra E. Amarasinghe

2015-07-01

Full Text Available Methylation has previously been associated with allele specific expression in ants. Recently, we found methylation is important in worker reproduction in the bumblebee Bombus terrestris. Here we searched for allele specific expression in twelve genes associated with worker reproduction in bees. We found allele specific expression in Ecdysone 20 monooxygenase and IMP-L2-like. Although we were unable to confirm a genetic or epigenetic cause for this allele specific expression, the expression patterns of the two genes match those predicted for imprinted genes.

Regulating expressin of cell and tissue-specific genes by modifying transcription

Energy Technology Data Exchange (ETDEWEB)

Beachy, Roger N. [Donald Danforth Plant Science Center, St. Louis, MO (United States); Dai, Shunhong [Donald Danforth Plant Science Center, St. Louis, MO (United States)

2009-12-15

Transcriptional regulation is the primary step to control gene expression, therefore function. Such regulation is achieved primarily via a combination of the activities of the promoter cis regulatory DNA elements and trans regulatory proteins that function through binding to these DNA elements. Our research supported by this program has led to the identification of rice bZIP transcription factors RF2a, RF2b and RLP1 that play key roles in regulating the activity of a vascular tissue specific promoter isolated from Rice Tungro Bacilliform Virus (RTBV) through their interactions with the Box II essential cis element located in the promoter. RF2a, RF2b and RLP1 possess multiple regulatory domains. Functional characterization reveals that those domains can activate or repress the activity of the RTBV promoter. Studies of transcriptional regulation of the RTBV promoter by this group of bZIP proteins not only provide insights about gene expression in the vascular tissue, but also insights about general mechanisms of transcription activation and repression. The knowledge gained from this research will also enable us to develop a well-described set of tools that can be used to control expression of multiple genes in transgenic plants and to improve biofuel feedstock.

Epigenetic repression of male gametophyte-specific genes in the Arabidopsis sporophyte

DEFF Research Database (Denmark)

Hoffmann, Robert D; Palmgren, Michael Broberg

2013-01-01

Tissue formation, the identity of cells, and the functions they fulfill, are results of gene regulation. The male gametophyte of plants, pollen, is outstanding in this respect as several hundred genes expressed in pollen are not expressed in the sporophyte. How pollen-specific genes are down......-regulated in the sporophyte has yet to be established. In this study, we have performed a bioinformatics analysis of publicly available genome-wide epigenetics data of several sporophytic tissues. By combining this analysis with DNase I footprinting data, we assessed means by which the repression of pollen-specific genes...

Sustainable energy transitions in emerging economies: The formation of a palm oil biomass waste-to-energy niche in Malaysia 1990–2011