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Sample records for expression patterns distinguish

  1. Specific micro-RNA expression patterns distinguish the basal and luminal subtypes of muscle-invasive bladder cancer

    PubMed Central

    Ochoa, Andrea E.; Choi, Woonyoung; Su, Xiaoping; Siefker-Radtke, Arlene; Czerniak, Bogdan; Dinney, Colin; McConkey, David J.

    2016-01-01

    The roles of non-coding RNAs in controlling clinical and biological heterogeneity in bladder cancer remain unclear. We used TCGA's published dataset (n = 405 tumors) as a discovery cohort and created a new validation cohort to define the miRNA expression patterns in the basal and luminal molecular subtypes of muscle-invasive bladder cancer (MIBC). We identified 63 miRNAs by PAM, which optimally identified basal and luminal tumors. The targets of the top luminal miRNAs were activators of EMT (ZEB1, ZEB2) and basal subtype transcription (IL-6, EGFR, STAT3), whereas the targets of the top basal miRNAs were involved in adipogenesis pathways and luminal breast cancer (ERBB2, ERBB3). We also identified a 15-miRNA signature that identified stromally infiltrated basal and luminal MIBCs corresponding to the “cluster IV/immune undifferentiated/claudin-low” and “cluster II/luminal immune” subtypes identified previously, which likely contain samples with higher infiltration rates. Using the 63-miRNA signature, we accurately assigned MIBCs to the basal and luminal subtypes and confirmed that patients with basal tumors had shorter overall survival. The results strongly suggest that miRNAs contribute to the control of the gene expression patterns observed in basal and luminal MIBCs and that they can be used as biomarkers and candidate therapeutic targets. PMID:27845906

  2. Specific micro-RNA expression patterns distinguish the basal and luminal subtypes of muscle-invasive bladder cancer.

    PubMed

    Ochoa, Andrea E; Choi, Woonyoung; Su, Xiaoping; Siefker-Radtke, Arlene; Czerniak, Bogdan; Dinney, Colin; McConkey, David J

    2016-12-06

    The roles of non-coding RNAs in controlling clinical and biological heterogeneity in bladder cancer remain unclear. We used TCGA's published dataset (n = 405 tumors) as a discovery cohort and created a new validation cohort to define the miRNA expression patterns in the basal and luminal molecular subtypes of muscle-invasive bladder cancer (MIBC). We identified 63 miRNAs by PAM, which optimally identified basal and luminal tumors. The targets of the top luminal miRNAs were activators of EMT (ZEB1, ZEB2) and basal subtype transcription (IL-6, EGFR, STAT3), whereas the targets of the top basal miRNAs were involved in adipogenesis pathways and luminal breast cancer (ERBB2, ERBB3). We also identified a 15-miRNA signature that identified stromally infiltrated basal and luminal MIBCs corresponding to the "cluster IV/immune undifferentiated/claudin-low" and "cluster II/luminal immune" subtypes identified previously, which likely contain samples with higher infiltration rates. Using the 63-miRNA signature, we accurately assigned MIBCs to the basal and luminal subtypes and confirmed that patients with basal tumors had shorter overall survival. The results strongly suggest that miRNAs contribute to the control of the gene expression patterns observed in basal and luminal MIBCs and that they can be used as biomarkers and candidate therapeutic targets.

  3. Career Patterns of Distinguished Male Social Scientists.

    ERIC Educational Resources Information Center

    Blackburn, Robert T.; Havighurst, Robert J.

    Seventy-four male eminent social scientists provided career stage data by which adult development theory was tested. All were born between 1893 and 1903 and met the criteria of a distinguished (and for several still active) scholarly career. The subjects were separated into four groups on the basis of their degree of productivity as of age 60.…

  4. Mastomys (rodentia: muridae) species distinguished by hemoglobin pattern differences.

    PubMed

    Robbins, C B; Krebs, J W; Johnson, K M

    1983-05-01

    Hemoglobin electrophoresis patterns were found to be reliable markers for distinguishing two species of Mastomys in Sierra Leone having 32 and 38 chromosomes. All 32-chromosome animals exhibited a single hemoglobin pattern, whereas those with 38-chromosomes had four distinguishable patterns. Both karyotypes were present throughout Sierra Leone. The 38-chromosome species was more prevalent in the Guinea savanna zone to the north, while the 32-chromosome species was most dominant in human-modified high forest areas of the eastern and southern parts of the country. In almost all situations the 32-chromosome species was more common in houses than in bush habitats; the reverse was true for Mastomys having 38 chromosomes. Analysis of hemoglobin patterns thus becomes useful for species identification, and is necessary to understand the roles of the different Mastomys forms as reservoirs of human diseases, such as Lassa fever in West Africa.

  5. Distinguishing Grammatical Constructions with fMRI Pattern Analysis

    ERIC Educational Resources Information Center

    Allen, Kachina; Pereira, Francisco; Botvinick, Matthew; Goldberg, Adele E.

    2012-01-01

    All linguistic and psycholinguistic theories aim to provide psychologically valid analyses of particular grammatical patterns and the relationships that hold among them. Until recently, no tools were available to distinguish neural correlates of particular grammatical constructions that shared the same content words, propositional meaning, and…

  6. Distinguishing Grammatical Constructions with fMRI Pattern Analysis

    ERIC Educational Resources Information Center

    Allen, Kachina; Pereira, Francisco; Botvinick, Matthew; Goldberg, Adele E.

    2012-01-01

    All linguistic and psycholinguistic theories aim to provide psychologically valid analyses of particular grammatical patterns and the relationships that hold among them. Until recently, no tools were available to distinguish neural correlates of particular grammatical constructions that shared the same content words, propositional meaning, and…

  7. Mathematically guided approaches to distinguish models of periodic patterning

    PubMed Central

    Hiscock, Tom W.; Megason, Sean G.

    2015-01-01

    How periodic patterns are generated is an open question. A number of mechanisms have been proposed – most famously, Turing's reaction-diffusion model. However, many theoretical and experimental studies focus on the Turing mechanism while ignoring other possible mechanisms. Here, we use a general model of periodic patterning to show that different types of mechanism (molecular, cellular, mechanical) can generate qualitatively similar final patterns. Observation of final patterns is therefore not sufficient to favour one mechanism over others. However, we propose that a mathematical approach can help to guide the design of experiments that can distinguish between different mechanisms, and illustrate the potential value of this approach with specific biological examples. PMID:25605777

  8. Mathematically guided approaches to distinguish models of periodic patterning.

    PubMed

    Hiscock, Tom W; Megason, Sean G

    2015-02-01

    How periodic patterns are generated is an open question. A number of mechanisms have been proposed--most famously, Turing's reaction-diffusion model. However, many theoretical and experimental studies focus on the Turing mechanism while ignoring other possible mechanisms. Here, we use a general model of periodic patterning to show that different types of mechanism (molecular, cellular, mechanical) can generate qualitatively similar final patterns. Observation of final patterns is therefore not sufficient to favour one mechanism over others. However, we propose that a mathematical approach can help to guide the design of experiments that can distinguish between different mechanisms, and illustrate the potential value of this approach with specific biological examples. © 2015. Published by The Company of Biologists Ltd.

  9. How bees distinguish patterns by green and blue modulation

    PubMed Central

    Horridge, Adrian

    2015-01-01

    In the 1920s, Mathilde Hertz found that trained bees discriminated between shapes or patterns of similar size by something related to total length of contrasting contours. This input is now interpreted as modulation in green and blue receptor channels as flying bees scan in the horizontal plane. Modulation is defined as total contrast irrespective of sign multiplied by length of edge displaying that contrast, projected to vertical, therefore, combining structure and contrast in a single input. Contrast is outside the eye; modulation is a phasic response in receptor pathways inside. In recent experiments, bees trained to distinguish color detected, located, and measured three independent inputs and the angles between them. They are the tonic response of the blue receptor pathway and modulation of small-field green or (less preferred) blue receptor pathways. Green and blue channels interacted intimately at a peripheral level. This study explores in more detail how various patterns are discriminated by these cues. The direction of contrast at a boundary was not detected. Instead, bees located and measured total modulation generated by horizontal scanning of contrasts, irrespective of pattern. They also located the positions of isolated vertical edges relative to other landmarks and distinguished the angular widths between vertical edges by green or blue modulation alone. The preferred inputs were the strongest green modulation signal and angular width between outside edges, irrespective of color. In the absence of green modulation, the remaining cue was a measure and location of blue modulation at edges. In the presence of green modulation, blue modulation was inhibited. Black/white patterns were distinguished by the same inputs in blue and green receptor channels. Left–right polarity and mirror images could be discriminated by retinotopic green modulation alone. Colors in areas bounded by strong green contrast were distinguished as more or less blue than the

  10. How bees distinguish patterns by green and blue modulation.

    PubMed

    Horridge, Adrian

    2015-01-01

    In the 1920s, Mathilde Hertz found that trained bees discriminated between shapes or patterns of similar size by something related to total length of contrasting contours. This input is now interpreted as modulation in green and blue receptor channels as flying bees scan in the horizontal plane. Modulation is defined as total contrast irrespective of sign multiplied by length of edge displaying that contrast, projected to vertical, therefore, combining structure and contrast in a single input. Contrast is outside the eye; modulation is a phasic response in receptor pathways inside. In recent experiments, bees trained to distinguish color detected, located, and measured three independent inputs and the angles between them. They are the tonic response of the blue receptor pathway and modulation of small-field green or (less preferred) blue receptor pathways. Green and blue channels interacted intimately at a peripheral level. This study explores in more detail how various patterns are discriminated by these cues. The direction of contrast at a boundary was not detected. Instead, bees located and measured total modulation generated by horizontal scanning of contrasts, irrespective of pattern. They also located the positions of isolated vertical edges relative to other landmarks and distinguished the angular widths between vertical edges by green or blue modulation alone. The preferred inputs were the strongest green modulation signal and angular width between outside edges, irrespective of color. In the absence of green modulation, the remaining cue was a measure and location of blue modulation at edges. In the presence of green modulation, blue modulation was inhibited. Black/white patterns were distinguished by the same inputs in blue and green receptor channels. Left-right polarity and mirror images could be discriminated by retinotopic green modulation alone. Colors in areas bounded by strong green contrast were distinguished as more or less blue than the

  11. Adaptive inference for distinguishing credible from incredible patterns in nature

    USGS Publications Warehouse

    Holling, Crawford S.; Allen, C.R.

    2002-01-01

    Strong inference is a powerful and rapid tool that can be used to identify and explain patterns in molecular biology, cell biology, and physiology. It is effective where causes are single and separable and where discrimination between pairwise alternative hypotheses can be determined experimentally by a simple yes or no answer. But causes in ecological systems are multiple and overlapping and are not entirely separable. Frequently, competing hypotheses cannot be distinguished by a single unambiguous test, but only by a suite of tests of different kinds, that produce a body of evidence to support one line of argument and not others. We call this process "adaptive inference". Instead of pitting each member of a pair of hypotheses against each other, adaptive inference relies on the exuberant invention of multiple, competing hypotheses, after which carefully structured comparative data are used to explore the logical consequences of each. Herein we present an example that demonstrates the attributes of adaptive inference that have developed out of a 30-year study of the resilience of ecosystems.

  12. Symptom patterns can distinguish diverticular disease from irritable bowel syndrome.

    PubMed

    Cuomo, Rosario; Barbara, Giovanni; Andreozzi, Paolo; Bassotti, Gabrio; Casetti, Tino; Grassini, Mario; Ierardi, Enzo; Maconi, Giovanni; Marchi, Santino; Sarnelli, Giovanni; Savarino, Vincenzo; Usai, Paolo; Vozzella, Letizia; Annibale, Bruno

    2013-11-01

    Diverticular disease (DD) and irritable bowel syndrome (IBS) share a similar symptom pattern. However, comparative studies are flawed by different age at onset of symptoms. We aimed to verify whether clinical features distinguish DD from IBS. Patients with DD or IBS, matched for age and gender (1/1) were consecutively recruited. Data on demographic parameters, voluptuary habits, inheritance of disease and symptoms were collected. Moreover, the association between pain > 24 h, and clinical parameters were evaluated. Ninety patients with DD and 90 patients with IBS (DD: F/M: 46/44; age: 50.9 years; IBS: 46/44; 50.4) were selected from an overall population of 1275 patients. Only nine patients with DD (10%) fulfilled the criteria for IBS diagnosis. Abdominal pain > 24 h was more prevalent in SDD than in patients with IBS (20 vs. 6 patients; P < 0.01). Furthermore, compared with IBS, patients with DD showed more episodes of pain > 24 h requiring medical attention (80% vs. 33%; P < 0.01). Abdominal pain lasting for more than 24 h discriminates patients with DD compared with those with IBS. Identifying this symptom could be an appropriate strategy to define the diagnosis and management. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  13. Gene Expression Patterns in Human Liver Cancers

    PubMed Central

    Chen, Xin; Cheung, Siu Tim; So, Samuel; Fan, Sheung Tat; Barry, Christopher; Higgins, John; Lai, Kin-Man; Ji, Jiafu; Dudoit, Sandrine; Ng, Irene O.L.; van de Rijn, Matt; Botstein, David; Brown, Patrick O.

    2002-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Using cDNA microarrays to characterize patterns of gene expression in HCC, we found consistent differences between the expression patterns in HCC compared with those seen in nontumor liver tissues. The expression patterns in HCC were also readily distinguished from those associated with tumors metastatic to liver. The global gene expression patterns intrinsic to each tumor were sufficiently distinctive that multiple tumor nodules from the same patient could usually be recognized and distinguished from all the others in the large sample set on the basis of their gene expression patterns alone. The distinctive gene expression patterns are characteristic of the tumors and not the patient; the expression programs seen in clonally independent tumor nodules in the same patient were no more similar than those in tumors from different patients. Moreover, clonally related tumor masses that showed distinct expression profiles were also distinguished by genotypic differences. Some features of the gene expression patterns were associated with specific phenotypic and genotypic characteristics of the tumors, including growth rate, vascular invasion, and p53 overexpression. PMID:12058060

  14. IMP2 expression distinguishes endometrioid from serous endometrial adenocarcinomas.

    PubMed

    Zhang, Liping; Liu, Yuxin; Hao, Suyang; Woda, Bruce A; Lu, Di

    2011-06-01

    Among various endometrial adenocarcinomas, endometrioid carcinoma can be very difficult to separate from serous carcinomas. Various biomarkers have been studied with proven value, including p53, Ki-67, and p16. In this study, we present data on another biomarker, IMP2, which we believe is sensitive and specific. Using 320 endometrial biopsy cases, we demonstrate that IMP2 is normally expressed in all proliferative and inactive endometrial glandular cells. The pattern of such expression is unchanged in serous carcinomas. IMP2 expression is, however, lost in all cases of endometrioid carcinomas by at least 25% to >95% of tumor cell populations. Therefore, loss of IMP2 expression can differentiate endometrioid from serous carcinomas. Such finding of IMP2 expression remained the same in mixed endometrioid and serous carcinomas; IMP2 expression is lost in all endometrioid components by at least 25% of tumor cell population, whereas it remained diffuse and strong in all serous components of carcinomas.

  15. Gene-expression profiling reveals distinct expression patterns for Classic versus Variant Merkel cell phenotypes and new classifier genes to distinguish Merkel cell from small-cell lung carcinoma.

    PubMed

    Van Gele, Mireille; Boyle, Glen M; Cook, Anthony L; Vandesompele, Jo; Boonefaes, Tom; Rottiers, Pieter; Van Roy, Nadine; De Paepe, Anne; Parsons, Peter G; Leonard, J Helen; Speleman, Frank

    2004-04-08

    Merkel cell carcinoma (MCC) is a rare aggressive skin tumor which shares histopathological and genetic features with small-cell lung carcinoma (SCLC), both are of neuroendocrine origin. Comparable to SCLC, MCC cell lines are classified into two different biochemical subgroups designated as 'Classic' and 'Variant'. With the aim to identify typical gene-expression signatures associated with these phenotypically different MCC cell lines subgroups and to search for differentially expressed genes between MCC and SCLC, we used cDNA arrays to profile 10 MCC cell lines and four SCLC cell lines. Using significance analysis of microarrays, we defined a set of 76 differentially expressed genes that allowed unequivocal identification of Classic and Variant MCC subgroups. We assume that the differential expression levels of some of these genes reflect, analogous to SCLC, the different biological and clinical properties of Classic and Variant MCC phenotypes. Therefore, they may serve as useful prognostic markers and potential targets for the development of new therapeutic interventions specific for each subgroup. Moreover, our analysis identified 17 powerful classifier genes capable of discriminating MCC from SCLC. Real-time quantitative RT-PCR analysis of these genes on 26 additional MCC and SCLC samples confirmed their diagnostic classification potential, opening opportunities for new investigations into these aggressive cancers.

  16. Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly.

    PubMed

    de Juan Romero, Camino; Bruder, Carl; Tomasello, Ugo; Sanz-Anquela, José Miguel; Borrell, Víctor

    2015-07-14

    Gyrencephalic species develop folds in the cerebral cortex in a stereotypic manner, but the genetic mechanisms underlying this patterning process are unknown. We present a large-scale transcriptomic analysis of individual germinal layers in the developing cortex of the gyrencephalic ferret, comparing between regions prospective of fold and fissure. We find unique transcriptional signatures in each germinal compartment, where thousands of genes are differentially expressed between regions, including ~80% of genes mutated in human cortical malformations. These regional differences emerge from the existence of discrete domains of gene expression, which occur at multiple locations across the developing cortex of ferret and human, but not the lissencephalic mouse. Complex expression patterns emerge late during development and map the eventual location of folds or fissures. Protomaps of gene expression within germinal layers may contribute to define cortical folds or functional areas, but our findings demonstrate that they distinguish the development of gyrencephalic cortices.

  17. Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly

    PubMed Central

    de Juan Romero, Camino; Bruder, Carl; Tomasello, Ugo; Sanz-Anquela, José Miguel; Borrell, Víctor

    2015-01-01

    Gyrencephalic species develop folds in the cerebral cortex in a stereotypic manner, but the genetic mechanisms underlying this patterning process are unknown. We present a large-scale transcriptomic analysis of individual germinal layers in the developing cortex of the gyrencephalic ferret, comparing between regions prospective of fold and fissure. We find unique transcriptional signatures in each germinal compartment, where thousands of genes are differentially expressed between regions, including ∼80% of genes mutated in human cortical malformations. These regional differences emerge from the existence of discrete domains of gene expression, which occur at multiple locations across the developing cortex of ferret and human, but not the lissencephalic mouse. Complex expression patterns emerge late during development and map the eventual location of folds or fissures. Protomaps of gene expression within germinal layers may contribute to define cortical folds or functional areas, but our findings demonstrate that they distinguish the development of gyrencephalic cortices. PMID:25916825

  18. Gene-expression profile comparisons distinguish seven organs of maize

    PubMed Central

    Cho, Yangrae; Fernandes, John; Kim, Soo-Hwan; Walbot, Virginia

    2002-01-01

    Background A maize array was fabricated with 5,376 unique expressed sequence tag (EST) clones sequenced from 4-day-old roots, immature ears and adult organ cDNA libraries. To elucidate organ relationships, relative mRNA levels were quantified by hybridization with embryos, three maize vegetative organs (leaf blades, leaf sheaths and roots) from multiple developmental stages, husk leaves and two types of floral organs (immature ears and silks). Results Clustering analyses of the hybridization data suggest that maize utilizes both the PEPCK and NADP-ME C4 photosynthetic routes as genes in these pathways are co-regulated. Husk RNA has a gene-expression profile more similar to floral organs than to vegetative leaves. Only 7% of the genes were highly organ specific, showing over a fourfold difference in at least one of 12 comparisons and 37% showed a two- to fourfold difference. The majority of genes were expressed in diverse organs with little difference in transcript levels. Cross-hybridization among closely related genes within multigene families could obscure tissue specificity. As a first step in elucidating individual gene-expression patterns, we show that 45-nucleotide oligo probes produce signal intensities and signal ratios comparable to PCR probes on the same matrix. Conclusions Gene-expression profile studies with cDNA microarrays provide a new molecular tool for defining plant organs and their relationships and for discovering new biological processes in silico. cDNA microarrays are insufficient for differentiating recently duplicated genes. Gene-specific oligo probes printed along with cDNA probes can query individual gene-expression profiles and gene families simultaneously. PMID:12225584

  19. Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism☆

    PubMed Central

    Lewis, Deborah A.; Suchindran, Sunil; Beckman, Michele G.; Hooper, W. Craig; Grant, Althea M.; Heit, John A.; Manco-Johnson, Marilyn; Moll, Stephan; Philipp, Claire S.; Kenney, Kristy; De Staercke, Christine; Pyle, Meredith E.; Chi, Jen-Tsan; Ortel, Thomas L.

    2015-01-01

    Introduction Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. There is limited understanding of the biological mechanisms that predispose patients to recurrent VTE. Objectives To identify whole blood gene expression profiles that distinguished patients with clinically distinct patterns of VTE. Patients/Methods We studied 107 patients with VTE separated into 3 groups: (1) ‘low-risk’ patients had one or more provoked VTE; (2) ‘moderate-risk’ patients had a single unprovoked VTE; (3) ‘high-risk’ patients had ≥2 unprovoked VTE. Each patient group was also compared to twenty-five individuals with no personal history of VTE. Total RNA from whole blood was isolated and hybridized to Illumina HT-12 V4 Beadchips to assay whole genome expression. Results Using class prediction analysis, we distinguished high-risk patients from low-risk patients and healthy controls with good receiver operating curve characteristics (AUC = 0.81 and 0.84, respectively). We also distinguished moderate-risk individuals and low-risk individuals from healthy controls with AUC’s of 0.69 and 0.80, respectively. Using differential expression analysis, we identified several genes previously implicated in thrombotic disorders by genetic analyses, including SELP, KLKB1, ANXA5, and CD46. Protein levels for several of the identified genes were not significantly different between the different groups. Conclusion Gene expression profiles are capable of distinguishing patients with different clinical presentations of VTE, and genes relevant to VTE risk are frequently differentially expressed in these comparisons. PMID:25684211

  20. Gene Expression Patterns in Ovarian Carcinomas

    PubMed Central

    Schaner, Marci E.; Ross, Douglas T.; Ciaravino, Giuseppe; Sørlie, Therese; Troyanskaya, Olga; Diehn, Maximilian; Wang, Yan C.; Duran, George E.; Sikic, Thomas L.; Caldeira, Sandra; Skomedal, Hanne; Tu, I-Ping; Hernandez-Boussard, Tina; Johnson, Steven W.; O'Dwyer, Peter J.; Fero, Michael J.; Kristensen, Gunnar B.; Børresen-Dale, Anne-Lise; Hastie, Trevor; Tibshirani, Robert; van de Rijn, Matt; Teng, Nelson N.; Longacre, Teri A.; Botstein, David; Brown, Patrick O.; Sikic, Branimir I.

    2003-01-01

    We used DNA microarrays to characterize the global gene expression patterns in surface epithelial cancers of the ovary. We identified groups of genes that distinguished the clear cell subtype from other ovarian carcinomas, grade I and II from grade III serous papillary carcinomas, and ovarian from breast carcinomas. Six clear cell carcinomas were distinguished from 36 other ovarian carcinomas (predominantly serous papillary) based on their gene expression patterns. The differences may yield insights into the worse prognosis and therapeutic resistance associated with clear cell carcinomas. A comparison of the gene expression patterns in the ovarian cancers to published data of gene expression in breast cancers revealed a large number of differentially expressed genes. We identified a group of 62 genes that correctly classified all 125 breast and ovarian cancer specimens. Among the best discriminators more highly expressed in the ovarian carcinomas were PAX8 (paired box gene 8), mesothelin, and ephrin-B1 (EFNB1). Although estrogen receptor was expressed in both the ovarian and breast cancers, genes that are coregulated with the estrogen receptor in breast cancers, including GATA-3, LIV-1, and X-box binding protein 1, did not show a similar pattern of coexpression in the ovarian cancers. PMID:12960427

  1. Expression noise and acetylation profiles distinguishes HDACs functions

    PubMed Central

    Weinberger, Leehee; Voichek, Yoav; Tirosh, Itay; Hornung, Gil; Amit, Ido; Barkai, Naama

    2012-01-01

    Gene expression shows a significant variation (noise) between genetically identical cells. Noise depends on the gene expression process regulated by the chromatin environment. We screened for chromatin factors that modulate noise in S. cerevisiae and analyzed the results using a theoretical model that infers regulatory mechanisms from the noise vs. mean relationship. Distinct activities of the Rpd3(L) and Set3 histone deacetylase complexes were predicted. Both HDACs repressed expression. Yet, Rpd3(L)C decreased the frequency of transcriptional bursts, while Set3C decreased the burst size, as did H2B mono-ubiquitination (ubH2B). We mapped the acetylation of H3 Lysine 9 (H3K9ac) upon deletion of multiple subunits of Set3C and Rpd3(L)C, and of ubH2B effectors. ubH2B and Set3C appear to function in the same pathway to reduce the probability that an elongating PolII produces a functional transcript (PolII processivity), while Rpd3(L)C likely represses gene expression at a step preceding elongation. PMID:22683268

  2. Multiple C4/Slp genes distinguished by expression after transfection.

    PubMed Central

    Robins, D M; Malissen, M; Hood, L; Ferreira, A; Walthall, D; Mitchell, M

    1986-01-01

    The S region of the murine major histocompatibility complex contains two closely related genes: C4, encoding the fourth component of complement, and Slp, encoding sex-limited protein. We cloned these genes from a cosmid library of the B10.W7R strain that does not show androgen regulation of the Slp protein. Restriction site polymorphisms revealed at least four C4-like genes within the Sw7 locus, indicating evolutionary amplification of this region. Transfection of these genes into L cells resulted in expression, processing, and secretion of immunologically correct C4 and Slp proteins. At least two different Slp genes and one C4 gene were capable, after transfection, of expressing C4 and Slp indistinguishable from macrophage-derived protein. A third Slp gene exists within this locus whose recombinant cognate did not express in L cells. Thus, the B10.W7R S region includes one C4 gene and at least three Slp-like genes. Images PMID:3023818

  3. A Small Set of Succinct Signature Patterns Distinguishes Chinese and Non-Chinese HIV-1 Genomes

    PubMed Central

    Wilms, Christoph; Heider, Dominik; Yang, Rongge; Hoffmann, Daniel

    2013-01-01

    The epidemiology of HIV-1 in China has unique features that may have led to unique viral strains. We therefore tested the hypothesis that it is possible to find distinctive patterns in HIV-1 genomes sampled in China. Using a rule inference algorithm we could indeed extract from sequences of the third variable loop (V3) of HIV-1 gp120 a set of 14 signature patterns that with 89% accuracy distinguished Chinese from non-Chinese sequences. These patterns were found to be specific to HIV-1 subtype, i.e. sequences complying with pattern 1 were of subtype B, pattern 2 almost exclusively covered sequences of subtype 01_AE, etc. We then analyzed the first of these signature patterns in depth, namely that L and W at two V3 positions are specifically occurring in Chinese sequences of subtype B/B' (3% false positives). This pattern was found to be in agreement with the phylogeny of HIV-1 of subtype B inside and outside of China. We could neither reject nor convincingly confirm that the pattern is stabilized by immune escape. For further interpretation of the signature pattern we used the recently developed measure of Direct Information, and in this way discovered evidence for physical interactions between V2 and V3. We conclude by a discussion of limitations of signature patterns, and the applicability of the approach to other genomic regions and other countries. PMID:23527028

  4. Distinguishing Pattern Formation Phenotypes: Applying Minkowski Functionals to Cell Biology Systems

    NASA Astrophysics Data System (ADS)

    Rericha, Erin; Guven, Can; Parent, Carole; Losert, Wolfgang

    2011-03-01

    Spatial Clustering of proteins within cells or cells themselves frequently occur in cell biology systems. However quantifying the underlying order and determining the regulators of these cluster patterns have proved difficult due to the inherent high noise levels in the systems. For instance the patterns formed by wild type and cyclic-AMP regulatory mutant Dictyostelium cells are visually distinctive, yet the large error bars in measurements of the fractal number, area, Euler number, eccentricity, and wavelength making it difficult to quantitatively distinguish between the patterns. We apply a spatial analysis technique based on Minkowski functionals and develop metrics which clearly separate wild type and mutant cell lines into distinct categories. Having such a metric facilitated the development of a computational model for cellular aggregation and its regulators. Supported by NIH-NGHS Nanotechnology (R01GM085574) and the Burroughs Wellcome Fund.

  5. Distinguishing diffuse alopecia areata (AA) from pattern hair loss (PHL) using CD3(+) T cells.

    PubMed

    Kolivras, Athanassios; Thompson, Curtis

    2016-05-01

    Distinguishing between diffuse subacute alopecia areata (AA), in which the peribulbar infiltrate is absent, and pattern hair loss is challenging, particularly in cases that lack marked follicular miniaturization and a marked catagen/telogen shift. We sought to distinguish diffuse AA from pattern hair loss using CD3(+) T lymphocytes. A total of 28 cases of subacute AA and 31 cases of pattern hair loss were selected and a 4-mm punch biopsy was performed. All the specimens were processed using the "HoVert" (horizontal and vertical) technique. In all cases, hematoxylin-eosin and immunohistochemical stains for CD3, CD4, CD8, and CD20 were performed. The presence of CD3(+) lymphocytes within empty follicular fibrous tracts (stela), even without a concomitant peribulbar infiltrate, is a reliable histopathological clue in supporting a diagnosis of AA (sensitivity 0.964, specificity 1, P ≤ .001). Limited tissue for analysis remained in the clinical sample tissue blocks. The presence of CD3(+) T-cells within empty follicular fibrous tracts (stela) supports a diagnosis of AA. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  6. Contrasting patterns of X/Y polymorphism distinguish Carica papaya from other sex chromosome systems.

    PubMed

    Weingartner, Laura A; Moore, Richard C

    2012-12-01

    The sex chromosomes of the tropical crop papaya (Carica papaya) are evolutionarily young and consequently allow for the examination of evolutionary mechanisms that drive early sex chromosome divergence. We conducted a molecular population genetic analysis of four X/Y gene pairs from a collection of 45 wild papaya accessions. These population genetic analyses reveal striking differences in the patterns of polymorphism between the X and Y chromosomes that distinguish them from other sex chromosome systems. In most sex chromosome systems, the Y chromosome displays significantly reduced polymorphism levels, whereas the X chromosome maintains a level of polymorphism that is comparable to autosomal loci. However, the four papaya sex-linked loci that we examined display diversity patterns that are opposite this trend: the papaya X alleles exhibit significantly reduced polymorphism levels, whereas the papaya Y alleles maintain greater than expected levels of diversity. Our analyses suggest that selective sweeps in the regions of the X have contributed to this pattern while also revealing geographically restricted haplogroups on the Y. We discuss the possible role sexual selection and/or genomic conflict have played in shaping the contrasting patterns of polymorphism found for the papaya X and Y chromosomes.

  7. Expert cardiologists cannot distinguish between Brugada phenocopy and Brugada syndrome electrocardiogram patterns.

    PubMed

    Gottschalk, Byron H; Anselm, Daniel D; Brugada, Josep; Brugada, Pedro; Wilde, Arthur A; Chiale, Pablo A; Pérez-Riera, Andres R; Elizari, Marcelo V; De Luna, Antoni Bayés; Krahn, Andrew D; Tan, Hanno L; Postema, Pieter G; Baranchuk, Adrian

    2016-07-01

    Brugada phenocopies (BrPs) are electrocardiogram (ECG) patterns that are identical to true Brugada syndrome (BrS) but are induced by various clinical conditions. The concept that both ECG patterns are visually identical has not been formally demonstrated. The aim of our study was to determine if experts on BrS were able to accurately distinguish between the BrS and BrP ECG patterns. Six ECGs from confirmed cases of BrS and six ECGs from previously published cases of BrP were included in the study. Surface 12-lead ECGs were scanned, saved in JPEG format, and sent to 10 international experts on BrS for evaluation (no clinical history provided). Evaluators were asked to label each case as a Brugada ECG pattern or non-Brugada ECG pattern by visual interpretation alone. The overall accuracy was 53 ± 33% for all cases. Within the BrS cases, the mean accuracy was 63 ± 34% and within the BrP cases, the mean accuracy was 43 ± 33%. Intra-observer repeatability was moderate (κ = 0.56) and inter-observer agreement was fair (κ = 0.36) while evaluator accuracy vs. the true diagnosis was only marginally better than chance (κ = 0.05). Similarly, diagnostic operating characteristics were poor (sensitivity 62%, specificity 43%, +LR 1.1, -LR 0.9). Our results provide strong evidence that BrP and BrS ECG patterns are visually identical and indistinguishable. These findings support the use of systematic diagnostic criteria for differentiating BrP vs. BrS as an erroneous diagnosis may have a negative impact on patient morbidity and mortality. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  8. Gene expression accurately distinguishes liver metastases of small bowel and pancreas neuroendocrine tumors.

    PubMed

    Sherman, Scott K; Maxwell, Jessica E; Carr, Jennifer C; Wang, Donghong; Bellizzi, Andrew M; Sue O'Dorisio, M; O'Dorisio, Thomas M; Howe, James R

    2014-12-01

    Small bowel (SBNETs) and pancreatic neuroendocrine tumors (PNETs) often present with liver metastases. Although liver biopsy establishes a neuroendocrine diagnosis, the primary tumor site is frequently unknown without exploratory surgery. Gene expression differences in metastases may distinguish primary SBNETs and PNETs. This study sought to determine expression differences of four genes in neuroendocrine metastases and to create a gene expression algorithm to distinguish the primary site. Nodal and liver metastases from SBNETs and PNETs (n = 136) were collected at surgery under an Institutional Review Board-approved protocol. Quantitative PCR measured expression of bombesin-like receptor-3, opioid receptor kappa-1, oxytocin receptor, and secretin receptor in metastases. Logistic regression models defined an algorithm predicting the primary tumor site. Models were developed on a training set of 21 nodal metastases and performance was validated on an independent set of nodal and liver metastases. Expression of all four genes was significantly different in SBNET compared to PNET metastases. The optimal model employed expression of bombesin-like receptor-3 and opioid receptor kappa-1. When these genes did not amplify, the algorithm used oxytocin receptor and secretin receptor expression, which allowed classification of all 136 metastases with 94.1 % accuracy. In the independent liver metastasis validation set, 52/56 (92.9 %) were correctly classified. Positive predictive values were 92.5 % for SBNETs and 93.8 % for PNETs. This validated algorithm accurately distinguishes SBNET and PNET metastases based on their expression of four genes. High accuracy in liver metastases demonstrates applicability to the clinical setting. Studies assessing this algorithm's utility in prospective clinical decision-making are warranted.

  9. Complex suppression patterns distinguish between major energy loss effects in Quark-Gluon Plasma

    NASA Astrophysics Data System (ADS)

    Djordjevic, Magdalena

    2016-12-01

    Interactions of high momentum partons with Quark-Gluon Plasma created in relativistic heavy-ion collisions provide an excellent tomography tool for this new form of matter. Recent measurements for charged hadrons and unidentified jets at the LHC show an unexpected flattening of the suppression curves at high momentum, exhibited when either momentum or the collision centrality is changed. Furthermore, a limited data available for B probes indicate a qualitatively different pattern, as nearly the same flattening is exhibited for the curves corresponding to two opposite momentum ranges. We here show that the experimentally measured suppression curves are well reproduced by our theoretical predictions, and that the complex suppression patterns are due to an interplay of collisional, radiative energy loss and the dead-cone effect. Furthermore, for B mesons, we predict that the uniform flattening of the suppression indicated by the limited dataset is in fact valid across the entire span of the momentum ranges, which will be tested by the upcoming experiments. Overall, the study presented here, provides a rare opportunity for pQCD theory to qualitatively distinguish between the major energy loss mechanisms at the same (nonintuitive) dataset.

  10. Differential vimentin expression in ovarian and uterine corpus endometrioid adenocarcinomas: diagnostic utility in distinguishing double primaries from metastatic tumors.

    PubMed

    Desouki, Mohamed M; Kallas, Sarah J; Khabele, Dineo; Crispens, Marta A; Hameed, Omar; Fadare, Oluwole

    2014-05-01

    This study aimed to assess the diagnostic value of vimentin expression in differentiating endometrioid adenocarcinoma of primary uterine corpus and ovarian origin. Immunohistochemical analyses for the expression of vimentin in tumoral epithelial cells were performed on 149 endometrioid adenocarcinomas wherein the primary sites were not in question, including whole tissue sections of 27 carcinomas of uterine corpus origin (and no synchronous ovarian tumor), 7 carcinomas of ovarian origin (and no synchronous uterine corpus tumor) and a tissue microarray (TMA) containing 91 primary uterine corpus and 24 primary ovarian carcinomas. We also assessed 15 cases that synchronously involved the uterine corpus and ovary, 15 cases of metastasis to organs/tissues other than uterine corpus or ovary as well as 7 lymph node metastases. Vimentin was negative in 97% (30/31) of primary ovarian carcinomas. In contrast, 82% (97/118) of primary uterine corpus carcinomas were vimentin-positive. Vimentin expression was discordant in 53% of synchronous tumors. The sensitivity and specificity of negative vimentin staining in predicting an ovarian primary were 97% and 82%, respectively, whereas parallel values for positive vimentin staining in predicting a primary uterine tumor were 82% and 97%, respectively. The pattern of vimentin expression in all cases was maintained in their respective regional lymph nodes and distant metastases. In conclusion, ovarian and uterine corpus endometrioid adenocarcinomas have different patterns of vimentin expression. If validated in larger and/or different data sets, these findings may have diagnostic value in distinguishing metastatic lesions from double primary tumors involving both sites.

  11. Infants' Perception of Dynamic Affective Expressions: Do Infants Distinguish Specific Expressions?

    ERIC Educational Resources Information Center

    Soken, Nelson H.; Pick, Anne D.

    1999-01-01

    A preferential looking procedure was used to investigate 7-month-olds' perception of positive and negative affective facial expressions in which a single vocal expression was concordant or discordant with the videotaped facial expression. Results indicated that 7-month-olds discriminated among happy, interested, angry, and sad expressions.…

  12. Patterns of salivary analytes provide diagnostic capacity for distinguishing chronic adult periodontitis from health.

    PubMed

    Ebersole, Jeffrey L; Schuster, Julie L; Stevens, Jason; Dawson, Dolph; Kryscio, Richard J; Lin, Yushin; Thomas, Mark V; Miller, Craig S

    2013-01-01

    Salivary biomarker discovery requires identification of analytes with high discriminatory capacity to distinguish disease from health, including day-to-day variations that occur in analyte levels. In this study, seven biomarkers associated with inflammatory and tissue destructive processes of periodontal disease were investigated. In a prospective cohort study design, analyte expression levels were determined in unstimulated whole saliva samples collected on multiple occasions from 30 healthy adults (i.e., orally and systemically) and 50 chronic adult periodontitis patients. Salivary levels of IL-1β, IL-6, MMP-8, and albumin were significantly elevated (5.4 to 12.6X) and levels of IFNα were consistently lower (8.7X) in periodontitis patients compared with the daily variation observed in healthy adults. ROC analyses of IL-1β, IL-6 and MMP-8 yielded areas under the curves of 0.963-0.984 for discriminating periodontitis from health. These results demonstrate that levels of salivary bioanalytes of patients who have periodontitis are uniquely different from normal levels found in healthy subjects, and a panel consisting of IL-1β, MMP-8 and IL-6 shows particular diagnostic potential.

  13. Expression of a family of noncoding mitochondrial RNAs distinguishes normal from cancer cells

    PubMed Central

    Burzio, Verónica A.; Villota, Claudio; Villegas, Jaime; Landerer, Eduardo; Boccardo, Enrique; Villa, Luisa L.; Martínez, Ronny; Lopez, Constanza; Gaete, Fancy; Toro, Viviana; Rodriguez, Ximena; Burzio, Luis O.

    2009-01-01

    We reported the presence in human cells of a noncoding mitochondrial RNA that contains an inverted repeat (IR) of 815 nucleotides (nt) covalently linked to the 5′ end of the mitochondrial 16S RNA (16S mtrRNA). The transcript contains a stem-loop structure and is expressed in human proliferating cells but not in resting cells. Here, we demonstrate that, in addition to this transcript, normal human proliferating cells in culture express 2 antisense mitochondrial transcripts. These transcripts also contain stem-loop structures but strikingly they are down-regulated in tumor cell lines and tumor cells present in 17 different tumor types. The differential expression of these transcripts distinguishes normal from tumor cells and might contribute a unique vision on cancer biology and diagnostics. PMID:19470459

  14. Cellular and biological evaluation and diagnostic immunohistochemistry of cytokeratin 15/19 expression in distinguishing cutaneous basal cell carcinoma.

    PubMed

    Ziari, Katayoun; Behdad, Behnoosh; Mohammadshahi, Ali; Pirasteh, Hamid Reza; Sharifi, Mohammad Davood; Dadpay, Masoomeh

    2015-05-01

    Recent studies have investigated the expression of proliferative markers, but little is known about the expression of cytokeratin 15 and 19 in different histological subtypes of basal cell carcinoma (BCC). We conducted cellular, biological, clinicopathological and immunohistochemical analysis on the manifestations of 8 BCC by hematoxylin and eosin stain (H&E) staining and immunohistochemistry and reviewed relevant literature. Microscopically, the tumor cells were multiple remarkable foci of epidermolytic hyperkeratosis with large pleomorphic nuclei and scant cytoplasm together with peripheral palisading and forming solid nests. Furthermore, the most tumors were composed of highly cellular areas with a homogenous population of round, ovoid and spindle cells, hyperchromatic nuclei, high cellular pleomorphism, high mitotic index and various morphologic patterns. Moreover, the tumors displayed an invasive growth, with positive expression of Cytokeratin 19 (CK19) and negative expression of CK15. Our study revealed that the expression of CK19 was associated with progression and invasion in cases with BCC and immunohistochemistry is indispensable in distinguishing this tumor from other types of cutaneous carcinoma. To our best knowledge, it may be a considerable biomarker to assess invasiveness of cutaneous-surface BCC and to guide clinical management of such tumors.

  15. Gene expression profiling distinguishes radiation-induced fibrosing alveolitis from alveolitis in mice.

    PubMed

    Paun, Alexandra; Lemay, Anne-Marie; Haston, Christina K

    2010-04-01

    Thoracic cavity radiotherapy is limited by the development of alveolitis and fibrosis in susceptible patients. To define the response to 18 Gy pulmonary irradiation in mice at the gene expression level and to identify pathways that may influence the alveolitis and fibrosis phenotypes, expression profiling was undertaken. Male mice of three strains, A/J (late alveolitis response), C3H/HeJ (C3H, early alveolitis response) and C57BL/6J (B6, fibrosis response), were exposed to thoracic radiation and euthanized when moribund, and lung tissue gene expression was assessed with microarrays. The responses of A/J and C3H mice were more similar to each other (60% of differentially expressed genes detected in both strains) than to that of B6 mice (17% overlap). Pathway analysis revealed the expression of complement and of B-cell proliferation and activation genes to distinguish fibrosis from the alveolitis response and cytokine interactions and intracellular signaling differed between A/J and C3H mice. A genomic approach was used to identify specific pathways that likely contribute to the lung response to radiation as fibrosis or alveolitis in mice.

  16. [Expression of CD48 as a live marker to distinguish division of hematopoietic stem cells].

    PubMed

    Yang, Xin; Zhang, Yu; Peng, Lu-Yun; Pang, Ya-Kun; Dong, Fang; Ji, Qing; Xu, Jing; Cheng, Tao; Yuan, Wei-Ping; Gao, Ying-Dai

    2014-06-01

    AF488(+) cells was significantly higher than that of AF488(-) cells (P < 0.05). The proliferation ability of AF488(-) cells was also significantly higher than AF488(+) cells (P < 0.05). It is concluded that the expression of CD48 can distinguish cell division of hematopoietic stem cells and can be used as a live marker for the loss of stemness. In comparison with the Numb protein staining, this method can be used in living cells, thus provides greater convenience for subsequent cell culture studies and cell transplantation experiments.

  17. Lung sound patterns help to distinguish congestive heart failure, chronic obstructive pulmonary disease, and asthma exacerbations.

    PubMed

    Wang, Zhen; Xiong, Ying Xia

    2012-01-01

    Although congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and asthma patients typically present with abnormal auscultatory findings on lung examination, respiratory sounds are not normally subjected to rigorous analysis. The aim of this study was to evaluate in detail the distribution of respiratory sound intensity in CHF, COPD, and asthma patients during acute exacerbation. Respiratory sounds throughout the respiratory cycle were captured and displayed using an acoustic-based imaging technique. Breath sound distribution was mapped to create a gray-scale sequence of two-dimensional images based on intensity of sound (vibration). Consecutive CHF (n = 22), COPD (n = 19), and asthma (n = 18) patients were imaged at the time of presentation to the emergency department (ED). Twenty healthy subjects were also enrolled as a comparison group. Geographical area of the images and respiratory sound patterns were quantitatively analyzed. In healthy volunteers and COPD patients, the median (interquartile range [IQR]) geographical areas of the vibration energy images were similar, at 75.6 (IQR = 6.0) and 75.8 (IQR = 10.8) kilopixels, respectively (p > 0.05). Compared to healthy volunteers and COPD patients, areas for CHF and asthma patients were smaller, at 66.9 (IQR = 9.9) and 53.9 (IQR = 15.6) kilopixels, respectively (p < 0.05). The geographic area ratios between the left and right lungs for healthy volunteers and CHF and COPD patients were 1.0 (IQR = 0.2), 1.0 (IQR = 0.2), and 1.0 (IQR = 0.1), respectively. Compared to healthy volunteers, the geographic area ratio between the left and right lungs for asthma patients was 0.5 (IQR = 0.4; p < 0.05). In healthy volunteers and CHF patients, the ratios of vibration energy values at peak inspiration and expiration (peak I/E ratio) were 4.6 (IQR = 4.4) and 4.7 (IQR = 3.5). In marked contrast, the peak I/E ratios of COPD and asthma patients were 3.4 (= 2.1) and 0.1 (IQR = 0.3; p < 0.05), respectively. The

  18. Gene expression signatures but not cell cycle checkpoint functions distinguish AT carriers from normal individuals

    PubMed Central

    Zhang, Liwen; Simpson, Dennis A.; Innes, Cynthia L.; Chou, Jeff; Bushel, Pierre R.; Paules, Richard S.; Kaufmann, William K.

    2013-01-01

    Ataxia telangiectasia (AT) is a rare autosomal recessive disease caused by mutations in the ataxia telangiectasia-mutated gene (ATM). AT carriers with one mutant ATM allele are usually not severely affected although they carry an increased risk of developing cancer. There has not been an easy and reliable diagnostic method to identify AT carriers. Cell cycle checkpoint functions upon ionizing radiation (IR)-induced DNA damage and gene expression signatures were analyzed in the current study to test for differential responses in human lymphoblastoid cell lines with different ATM genotypes. While both dose- and time-dependent G1 and G2 checkpoint functions were highly attenuated in ATM−/− cell lines, these functions were preserved in ATM+/− cell lines equivalent to ATM+/+ cell lines. However, gene expression signatures at both baseline (consisting of 203 probes) and post-IR treatment (consisting of 126 probes) were able to distinguish ATM+/− cell lines from ATM+/+ and ATM−/− cell lines. Gene ontology (GO) and pathway analysis of the genes in the baseline signature indicate that ATM function-related categories, DNA metabolism, cell cycle, cell death control, and the p53 signaling pathway, were overrepresented. The same analyses of the genes in the IR-responsive signature revealed that biological categories including response to DNA damage stimulus, p53 signaling, and cell cycle pathways were overrepresented, which again confirmed involvement of ATM functions. The results indicate that AT carriers who have unaffected G1 and G2 checkpoint functions can be distinguished from normal individuals and AT patients by expression signatures of genes related to ATM functions. PMID:23943852

  19. Dynamic Gene Expression in the Human Cerebral Cortex Distinguishes Children from Adults

    PubMed Central

    Sterner, Kirstin N.; Weckle, Amy; Chugani, Harry T.; Tarca, Adi L.; Sherwood, Chet C.; Hof, Patrick R.; Kuzawa, Christopher W.; Boddy, Amy M.; Abbas, Asad; Raaum, Ryan L.; Grégoire, Lucie; Lipovich, Leonard; Grossman, Lawrence I.; Uddin, Monica; Wildman, Derek E.

    2012-01-01

    In comparison with other primate species, humans have an extended juvenile period during which the brain is more plastic. In the current study we sought to examine gene expression in the cerebral cortex during development in the context of this adaptive plasticity. We introduce an approach designed to discriminate genes with variable as opposed to uniform patterns of gene expression and found that greater inter-individual variance is observed among children than among adults. For the 337 transcripts that show this pattern, we found a significant overrepresentation of genes annotated to the immune system process (pFDR≅0). Moreover, genes known to be important in neuronal function, such as brain-derived neurotrophic factor (BDNF), are included among the genes more variably expressed in childhood. We propose that the developmental period of heightened childhood neuronal plasticity is characterized by more dynamic patterns of gene expression in the cerebral cortex compared to adulthood when the brain is less plastic. That an overabundance of these genes are annotated to the immune system suggests that the functions of these genes can be thought of not only in the context of antigen processing and presentation, but also in the context of nervous system development. PMID:22666384

  20. Children with postsurgical capillary leak syndrome can be distinguished by antigen expression on neutrophils and monocytes

    NASA Astrophysics Data System (ADS)

    Tarnok, Attila; Pipek, Michal; Valet, Guenter; Richter, Jacqueline; Hambsch, Joerg; Schneider, Peter

    1999-04-01

    Our initial studies indicate that children who develop post- operative capillary leak syndrome (CLS) following cardiac surgery with cardiopulmonary bypass (CPB) can be distinguished based on their pre-operative level of circulating cytokines an adhesion molecules. We tested flow cytometric analysis of surface antigen expression as a potential assay for risk assessment of CLS. 24th preoperative blood samples were stained with monoclonal antibodies for the adhesion molecules ICAM-1, LFA1, MAC1, (beta) -integrin, activation markers CD25, CD54, CD69, HLA- DR, CD14 or CD4. Cells were measured on a dual-laser flow cytometer calibrated with microbeads. Antigen expression was detected as mean fluorescence intensity. The data indicate, that neutrophils of CLS patients express preoperatively higher levels of LFA1 and monocytes higher levels of HLA-DR and activation markers thus are in a state of activation. This could in combination with surgical trauma and CPB lead to their additional stimulation and migration into sites of inflammation and induce postoperative CLS. It is planned to set up a Flow-Classification program for individual risk assessment. By discriminate analysis over 80 percent of the patients were correctly classified. Our preliminary study indicates that flow cytometry with its low samples requirements and rapid access of the results could be a powerful tool to perform risk assessment prior to pediatric open heart surgery.

  1. Extracellular matrix and cytochrome P450 gene expression can distinguish steatohepatitis from steatosis in mice

    PubMed Central

    Hennig, Ewa E; Mikula, Michal; Goryca, Krzysztof; Paziewska, Agnieszka; Ledwon, Joanna; Nesteruk, Monika; Woszczynski, Marek; Walewska-Zielecka, Bozena; Pysniak, Kazimiera; Ostrowski, Jerzy

    2014-01-01

    One of the main questions regarding nonalcoholic fatty liver disease is the molecular background of the transition from simple steatosis (SS) to the inflammatory and fibrogenic condition of steatohepatitis (NASH). We examined the gene expression changes during progression from histologically normal liver to SS and NASH in models of obesity caused by hyperphagia or a high-fat diet. Microarray-based analysis revealed that the expression of 1445 and 264 probe sets was changed exclusively in SS and NASH samples, respectively, and 1577 probe sets were commonly altered in SS and NASH samples. Functional annotations indicated that transcriptome alterations that were common for NASH and SS, as well as exclusive for NASH, involved extracellular matrix (ECM)-related processes, although they differed in the type of matrix structure change. The expression of 80 genes was significantly changed in all three comparisons: SS versus control, NASH versus control and NASH versus SS. Of these genes, epithelial membrane protein 1, IKBKB interacting protein and decorin were progressively up-regulated in both SS and NASH compared to normal tissue. The molecular context of interactions of encoded 80 proteins revealed that they are highly interconnected and significantly enriched for processes involving metabolism by cytochrome P450. Validation of 10 selected mRNAs encoding genes related to ECM and cytochrome P450 with quantitative RT-PCR analysis showed consistent changes in their expression during NASH development. The expression profile of these genes has the potential to distinguish NASH from SS and normal tissue and may possibly be beneficial in the clinical diagnosis of NASH. PMID:24913135

  2. p130/p107 expression distinguishes adipogenic potential in primary myoblasts based on age.

    PubMed

    Guan, Yu; Taylor-Jones, Jane M; Peterson, Charlotte A; McGehee, Robert E

    2002-09-06

    Recent investigations have provided significant evidence that many mesodermally derived tissues contain stem cell-like precursors capable of being stimulated to undergo differentiation into a variety of cellular lineages. We have recently reported that primary myoblasts isolated from 23-month-old mice have an increased adipogenic potential when compared to their 8-month-old counterparts. To further characterize the degree of adipocyte differentiation in these myoblasts, we examined early and late markers of adipocyte differentiation. Within the first 24h of adipocyte differentiation, expression of p130 and p107, two members of the retinoblastoma tumor suppressor gene family, are regulated and this event is an important one early in adipogenesis. Consistent with the increased adipogenic potential of the older myoblasts and in contrast to the younger cells, the p130:p107 pattern of expression is very similar to that observed in adipogenesis where there is a transient increase in p107 expression accompanied by a decrease in p130 expression. Interestingly, while these older cells accumulated lipid and expressed genes associated with lipid metabolism, they failed to express adipsin and leptin, two well-established markers of terminal adipocyte differentiation. These results suggest that older myoblasts are capable of initiating and progressing through the adipogenic program to a point where they express genes associated with lipid metabolism, but do not reach a terminally differentiated state. This finding may have important metabolic implications in the aging population.

  3. Extracting patterns of morphometry distinguishing HIV associated neurodegeneration from mild cognitive impairment via group cardinality constrained classification.

    PubMed

    Zhang, Yong; Kwon, Dongjin; Esmaeili-Firidouni, Pardis; Pfefferbaum, Adolf; Sullivan, Edith V; Javitz, Harold; Valcour, Victor; Pohl, Kilian M

    2016-12-01

    HIV-Associated Neurocognitive Disorder (HAND) is the most common constellation of cognitive dysfunctions in chronic HIV infected patients age 60 or older in the U.S. Only few published methods assist in distinguishing HAND from other forms of age-associated cognitive decline, such as Mild Cognitive Impairment (MCI). In this report, a data-driven, nonparameteric model to identify morphometric patterns separating HAND from MCI due to non-HIV conditions in this older age group was proposed. This model enhanced the potential for group separation by combining a smaller, longitudinal data set containing HAND samples with a larger, public data set including MCI cases. Using cross-validation, a linear model on healthy controls to harmonize the volumetric scores extracted from MRIs for demographic and acquisition differences between the two independent, disease-specific data sets was trained. Next, patterns distinguishing HAND from MCI via a group sparsity constrained logistic classifier were identified. Unlike existing approaches, our classifier directly solved the underlying minimization problem by decoupling the minimization of the logistic regression function from enforcing the group sparsity constraint. The extracted patterns consisted of eight regions that distinguished HAND from MCI on a significant level while being indifferent to differences in demographics and acquisition between the two sets. Individually selecting regions through conventional morphometric group analysis resulted in a larger number of regions that were less accurate. In conclusion, simultaneously analyzing all brain regions and time points for disease specific patterns contributed to distinguishing with high accuracy HAND-related impairment from cognitive impairment found in the HIV uninfected, MCI cohort. Hum Brain Mapp 37:4523-4538, 2016. © 2016 Wiley Periodicals, Inc.

  4. Can We Distinguish Emotions from Faces? Investigation of Implicit and Explicit Processes of Peak Facial Expressions

    PubMed Central

    Xiao, Ruiqi; Li, Xianchun; Li, Lin; Wang, Yanmei

    2016-01-01

    Most previous studies on facial expression recognition have focused on the moderate emotions; to date, few studies have been conducted to investigate the explicit and implicit processes of peak emotions. In the current study, we used transiently peak intense expression images of athletes at the winning or losing point in competition as materials, and investigated the diagnosability of peak facial expressions at both implicit and explicit levels. In Experiment 1, participants were instructed to evaluate isolated faces, isolated bodies, and the face-body compounds, and eye-tracking movement was recorded. The results revealed that the isolated body and face-body congruent images were better recognized than isolated face and face-body incongruent images, indicating that the emotional information conveyed by facial cues was ambiguous, and the body cues influenced facial emotion recognition. Furthermore, eye movement records showed that the participants displayed distinct gaze patterns for the congruent and incongruent compounds. In Experiment 2A, the subliminal affective priming task was used, with faces as primes and bodies as targets, to investigate the unconscious emotion perception of peak facial expressions. The results showed that winning face prime facilitated reaction to winning body target, whereas losing face prime inhibited reaction to winning body target, suggesting that peak facial expressions could be perceived at the implicit level. In general, the results indicate that peak facial expressions cannot be consciously recognized but can be perceived at the unconscious level. In Experiment 2B, revised subliminal affective priming task and a strict awareness test were used to examine the validity of unconscious perception of peak facial expressions found in Experiment 2A. Results of Experiment 2B showed that reaction time to both winning body targets and losing body targets was influenced by the invisibly peak facial expression primes, which indicated the

  5. Can We Distinguish Emotions from Faces? Investigation of Implicit and Explicit Processes of Peak Facial Expressions.

    PubMed

    Xiao, Ruiqi; Li, Xianchun; Li, Lin; Wang, Yanmei

    2016-01-01

    Most previous studies on facial expression recognition have focused on the moderate emotions; to date, few studies have been conducted to investigate the explicit and implicit processes of peak emotions. In the current study, we used transiently peak intense expression images of athletes at the winning or losing point in competition as materials, and investigated the diagnosability of peak facial expressions at both implicit and explicit levels. In Experiment 1, participants were instructed to evaluate isolated faces, isolated bodies, and the face-body compounds, and eye-tracking movement was recorded. The results revealed that the isolated body and face-body congruent images were better recognized than isolated face and face-body incongruent images, indicating that the emotional information conveyed by facial cues was ambiguous, and the body cues influenced facial emotion recognition. Furthermore, eye movement records showed that the participants displayed distinct gaze patterns for the congruent and incongruent compounds. In Experiment 2A, the subliminal affective priming task was used, with faces as primes and bodies as targets, to investigate the unconscious emotion perception of peak facial expressions. The results showed that winning face prime facilitated reaction to winning body target, whereas losing face prime inhibited reaction to winning body target, suggesting that peak facial expressions could be perceived at the implicit level. In general, the results indicate that peak facial expressions cannot be consciously recognized but can be perceived at the unconscious level. In Experiment 2B, revised subliminal affective priming task and a strict awareness test were used to examine the validity of unconscious perception of peak facial expressions found in Experiment 2A. Results of Experiment 2B showed that reaction time to both winning body targets and losing body targets was influenced by the invisibly peak facial expression primes, which indicated the

  6. Differential gene detection incorporating common expression patterns

    NASA Astrophysics Data System (ADS)

    Oba, Shigeyuki; Ishii, Shin

    2009-12-01

    In detection of differentially expressed (DE) genes between different groups of samples based on a high-throughput expression measurement system, we often use a classical statistical testing based on a simple assumption that the expression of a certain DE gene in one group is higher or lower in average than that in the other group. Based on this simple assumption, the theory of optimal discovery procedure (ODP) (Storey, 2005) provided an optimal thresholding function for DE gene detection. However, expression patterns of DE genes over samples may have such a structure that is not exactly consistent with group labels assigned to the samples. Appropriate treatment of such a structure can increase the detection ability. Namely, genes showing similar expression patterns to other biologically meaningful genes can be regarded as statistically more significant than those showing expression patterns independent of other genes, even if differences in mean expression levels are comparable. In this study, we propose a new statistical thresholding function based on a latent variable model incorporating expression patterns together with the ODP theory. The latent variable model assumes hidden common signals behind expression patterns over samples and the ODP theory is extended to involve the latent variables. When applied to several gene expression data matrices which include cluster structures or 'cancer outlier' structures, the newly-proposed thresholding functions showed prominently better detection performance of DE genes than the original ODP thresholding function did. We also demonstrate how the proposed methods behave through analyses of real breast cancer and lymphoma datasets.

  7. Signal and noise in vegetation patterns in drylands: distinguishing the baby from the bath water

    NASA Astrophysics Data System (ADS)

    Parsons, Anthony; Wainwright, John; Stewart, Jill; Okin, Gregory

    2014-05-01

    Patterns, and particularly banded patterns, are widely reported in dryland vegetation, and have been the subject of considerable modelling effort. However, much of this modelling effort is predicated on a mathematical approach that is designed to produce patterns and relies on physical processes that are unreasonable. In consequence, whereas in nature dryland vegetation patterns are irregular, disjointed and discontinuous, those produced by such models tend to be regular, continuous and even. The question, therefore, arises "Is it the irregularity, disjointed and discontinuous character of these patterns that holds the key to their formation rather than any apparent, human-imposed semblance of regularity and continuity?" By focusing on this apparent patterning have such models rejected as noise the key to understanding the signal? Models that produce regular vegetation patterns, typically do so by imposing global rules (largely for the distribution of water). Is it not more likely that vegetation responds to the local supply of water, nutrients and propagules? Here, we present a model for the growth of vegetation in deserts that is predicated on the local conditions of input of water, nutrients and propagules and output, such as loss of biomass by herbivory. The approach represents our best quantitative understanding of how desert ecosystems work. Patterns emerge that show the irregularity and discontinuity seen in nature. By focusing on the process rather than the patterns per se our model has the ability to address specific questions of the role of such patterns in land degradation. Further, it has the potential to provide quantitative estimates of the response of the landscape to specific management strategies, as well as the identification of the key thresholds and tipping points that are so important to the management of drylands. In providing a way to understand and predict the vegetation patterns that may develop during desertification, the approach also

  8. On the Unity of Children's Phonological Error Patterns: Distinguishing Symptoms from the Problem

    ERIC Educational Resources Information Center

    Dinnsen, Daniel A.

    2011-01-01

    This article compares the claims of rule- and constraint-based accounts of three seemingly distinct error patterns, namely, Deaffrication, Consonant Harmony and Assibilation, in the sound system of a child with a phonological delay. It is argued that these error patterns are not separate problems, but rather are symptoms of a larger conspiracy to…

  9. On the Unity of Children's Phonological Error Patterns: Distinguishing Symptoms from the Problem

    ERIC Educational Resources Information Center

    Dinnsen, Daniel A.

    2011-01-01

    This article compares the claims of rule- and constraint-based accounts of three seemingly distinct error patterns, namely, Deaffrication, Consonant Harmony and Assibilation, in the sound system of a child with a phonological delay. It is argued that these error patterns are not separate problems, but rather are symptoms of a larger conspiracy to…

  10. The Role of Neuropeptide Y mRNA Expression Level in Distinguishing Different Types of Depression.

    PubMed

    Yue, Yingying; Jiang, Haitang; Yin, Yingying; Zhang, Yuqun; Liang, Jinfeng; Li, Shenghua; Wang, Jun; Lu, Jianxin; Geng, Deqin; Wu, Aiqin; Yuan, Yonggui

    2016-01-01

    Previous studies demonstrate that the protein of neuropeptide Y (NPY) is abnormal in depression patients, but the changes of NPY in different types of depression are unclear. This study was aimed to examine protein and mRNA expression levels of NPY in 159 cases with four groups including post-stroke depression (PSD) group, stroke without depression (Non-PSD) group, major depressive disorder (MDD) group and normal control (NC) group. The protein and gene expression analysis were performed by enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction-based methods. One way analysis of variance (ANOVA), chi-square tests and nonparametric test were used to evaluate general characteristics, clinical and biological materials. In order to explore the role of NPY in different types of depression, the partial correlations, binary logistic regression analysis and receiver operating characteristic (ROC) curve were calculated for PSD and MDD groups. There are significant differences of NPY protein (Fdf(3) = 5.167, P = 0.002) and mRNA expression levels ([Formula: see text] = 20.541, P < 0.001) among four groups. Bonferroni multiple comparisons found that the NPY protein was significantly decreased in PSD (FBonferroni = -7.133, P = 0.002) and Non-PSD group (FBonferroni = -5.612, P = 0.018) compared with NC group. However, contrasted with MDD group, the mRNA expression was increased in PSD and Non-PSD group by nonparametric test (all P < 0.05). In binary logistic analyses, NPY mRNA expression was independent predictors of PSD (odds ratio: 1.452, 95% CI, 1.081-1.951, P = 0.013). The ROC curve showed NPY mRNA had a general prognostic accuracy (area under the curve: 0.766, 95% CI, 0.656-0.876, P < 0.001). This is the first study to explore the distinguishing function of NPY in different types of depression. It will provide help in the identification of different subtypes of depression.

  11. The Role of Neuropeptide Y mRNA Expression Level in Distinguishing Different Types of Depression

    PubMed Central

    Yue, Yingying; Jiang, Haitang; Yin, Yingying; Zhang, Yuqun; Liang, Jinfeng; Li, Shenghua; Wang, Jun; Lu, Jianxin; Geng, Deqin; Wu, Aiqin; Yuan, Yonggui

    2016-01-01

    Previous studies demonstrate that the protein of neuropeptide Y (NPY) is abnormal in depression patients, but the changes of NPY in different types of depression are unclear. This study was aimed to examine protein and mRNA expression levels of NPY in 159 cases with four groups including post-stroke depression (PSD) group, stroke without depression (Non-PSD) group, major depressive disorder (MDD) group and normal control (NC) group. The protein and gene expression analysis were performed by enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction-based methods. One way analysis of variance (ANOVA), chi-square tests and nonparametric test were used to evaluate general characteristics, clinical and biological materials. In order to explore the role of NPY in different types of depression, the partial correlations, binary logistic regression analysis and receiver operating characteristic (ROC) curve were calculated for PSD and MDD groups. There are significant differences of NPY protein (Fdf(3) = 5.167, P = 0.002) and mRNA expression levels (χKruskal2-Wallis, df(3) = 20.541, P < 0.001) among four groups. Bonferroni multiple comparisons found that the NPY protein was significantly decreased in PSD (FBonferroni = −7.133, P = 0.002) and Non-PSD group (FBonferroni = −5.612, P = 0.018) compared with NC group. However, contrasted with MDD group, the mRNA expression was increased in PSD and Non-PSD group by nonparametric test (all P < 0.05). In binary logistic analyses, NPY mRNA expression was independent predictors of PSD (odds ratio: 1.452, 95% CI, 1.081–1.951, P = 0.013). The ROC curve showed NPY mRNA had a general prognostic accuracy (area under the curve: 0.766, 95% CI, 0.656–0.876, P < 0.001). This is the first study to explore the distinguishing function of NPY in different types of depression. It will provide help in the identification of different subtypes of depression. PMID:28082897

  12. On the unity of children's phonological error patterns: distinguishing symptoms from the problem.

    PubMed

    Dinnsen, Daniel A

    2011-11-01

    This article compares the claims of rule- and constraint-based accounts of three seemingly distinct error patterns, namely, Deaffrication, Consonant Harmony and Assibilation, in the sound system of a child with a phonological delay. It is argued that these error patterns are not separate problems, but rather are symptoms of a larger conspiracy to avoid word-initial coronal stops. The clinical implications of these findings are also considered.

  13. On the unity of children’s phonological error patterns: Distinguishing symptoms from the problem

    PubMed Central

    Dinnsen, Daniel A.

    2012-01-01

    This article compares the claims of rule- and constraint-based accounts of three seemingly distinct error patterns, namely, Deaffrication, Consonant Harmony and Assibilation, in the sound system of a child with a phonological delay. It is argued that these error patterns are not separate problems, but rather are symptoms of a larger conspiracy to avoid word-initial coronal stops. The clinical implications of these findings are also considered. PMID:21787147

  14. Generalized Rydelek-Sacks test for distinguishing between periodic and random patterns in seismicity

    NASA Astrophysics Data System (ADS)

    Wu, Zhong-Liang

    1999-09-01

    For distinguishing the periodicity of strong earthquakes on the time scale of decades, we generalized the Rydelek-Sacks test (Rydelek, Sacks, 1989) to explore whether a time series is modulated by a periodic process or not. The test is conducted by comparing the total phasor of seismicity with that produced by a random Brownian motion. The phase angle is defined by the origin time of earthquakes relative to a reference time scale. Using this method we tested two hypotheses in geodynamics and earthquake prediction study. One is the hypothesis of Romanowicz (1993) who proposed that the great earthquakes alternate in a predictable fashion between strike-slip and thrusting mechanisms on a 20 30 years cycle. The other hypothesis is that the strong earthquakes in and around China have an active period of about ten years. The test obtains a negative conclusion for the former hypothesis and a positive conclusion for the latter at the 95% confidence level.

  15. Synchronous pattern distinguishes resting tremor associated with essential tremor from rest tremor of Parkinson's disease.

    PubMed

    Nisticò, R; Pirritano, D; Salsone, M; Novellino, F; Del Giudice, F; Morelli, M; Trotta, M; Bilotti, G; Condino, F; Cherubini, A; Valentino, P; Quattrone, A

    2011-01-01

    Rest tremor associated with essential tremor (ET) is a condition that poses challenges in diagnosing Parkinson's disease (PD). We investigated tremor parameters in PD and ET patients with rest tremor. Fifteen patients with PD and 15 patients with ET underwent electrophysiological examination to evaluate characteristics of muscle bursting in rest postures. Rest tremor amplitude of PD patients was significantly higher than that of patients with ET (p = 0.002), whereas burst duration and frequency were significantly higher in ET than in PD group (p = 0.002, p < 0.001, respectively). Patients with PD, however, showed some overlap of these electrophysiological values with values from patients with ET. By contrast, rest tremor pattern showed no overlap between the two diseases, because all patients with ET presented a synchronous pattern whereas PD patients had an alternating pattern (p < 0.001), a finding that differentiated the patients on an individual basis. The electromyographic pattern of rest tremor may help to differentiate PD from ET.

  16. Pattern analysis of serum proteome distinguishes renal cell carcinoma from other urologic diseases and healthy persons.

    PubMed

    Won, Yonggwan; Song, Ho-Jun; Kang, Taek Won; Kim, Jung-Ja; Han, Byoung-Don; Lee, Seung-Won

    2003-12-01

    Despite having a relatively low incidence, renal cell carcinoma (RCC) is one of the most lethal urologic cancers. For successful treatment including surgery, early detection is essential. Currently there is no screening method such as biomarker assays for early diagnosis of RCC. Surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF) is a recent technical advance that can be used to identify biomarkers for cancers. In this study, we investigated whether SELDI protein profiling and artificial intelligence analysis of serum could distinguish RCC from healthy persons and other urologic diseases (nonRCC). The SELDI-TOF data was acquired from a total of 36 serum samples with weak cation exchange-2 protein chip arrays and filtered using ProteinChip software. We used a decision tree algorithm c4.5 to classify the three groups of sera. Five proteins were identified with masses of 3900, 4107, 4153, 5352, and 5987 Da. These biomarkers can correctly separate RCC from healthy and nonRCC samples.

  17. Use of forecasting signatures to help distinguish periodicity, randomness, and chaos in ripples and other spatial patterns.

    PubMed

    Rubin, David M.

    1992-10-01

    Forecasting of one-dimensional time series previously has been used to help distinguish periodicity, chaos, and noise. This paper presents two-dimensional generalizations for making such distinctions for spatial patterns. The techniques are evaluated using synthetic spatial patterns and then are applied to a natural example: ripples formed in sand by blowing wind. Tests with the synthetic patterns demonstrate that the forecasting techniques can be applied to two-dimensional spatial patterns, with the same utility and limitations as when applied to one-dimensional time series. One limitation is that some combinations of periodicity and randomness exhibit forecasting signatures that mimic those of chaos. For example, sine waves distorted with correlated phase noise have forecasting errors that increase with forecasting distance, errors that are minimized using nonlinear models at moderate embedding dimensions, and forecasting properties that differ significantly between the original and surrogates. Ripples formed in sand by flowing air or water typically vary in geometry from one to another, even when formed in a flow that is uniform on a large scale; each ripple modifies the local flow or sand-transport field, thereby influencing the geometry of the next ripple downcurrent. Spatial forecasting was used to evaluate the hypothesis that such a deterministic process-rather than randomness or quasiperiodicity-is responsible for the variation between successive ripples. This hypothesis is supported by a forecasting error that increases with forecasting distance, a greater accuracy of nonlinear relative to linear models, and significant differences between forecasts made with the original ripples and those made with surrogate patterns. Forecasting signatures cannot be used to distinguish ripple geometry from sine waves with correlated phase noise, but this kind of structure can be ruled out by two geometric properties of the ripples: Successive ripples are highly

  18. Use of forecasting signatures to help distinguish periodicity, randomness, and chaos in ripples and other spatial patterns

    USGS Publications Warehouse

    Rubin, D.M.

    1992-01-01

    Forecasting of one-dimensional time series previously has been used to help distinguish periodicity, chaos, and noise. This paper presents two-dimensional generalizations for making such distinctions for spatial patterns. The techniques are evaluated using synthetic spatial patterns and then are applied to a natural example: ripples formed in sand by blowing wind. Tests with the synthetic patterns demonstrate that the forecasting techniques can be applied to two-dimensional spatial patterns, with the same utility and limitations as when applied to one-dimensional time series. One limitation is that some combinations of periodicity and randomness exhibit forecasting signatures that mimic those of chaos. For example, sine waves distorted with correlated phase noise have forecasting errors that increase with forecasting distance, errors that, are minimized using nonlinear models at moderate embedding dimensions, and forecasting properties that differ significantly between the original and surrogates. Ripples formed in sand by flowing air or water typically vary in geometry from one to another, even when formed in a flow that is uniform on a large scale; each ripple modifies the local flow or sand-transport field, thereby influencing the geometry of the next ripple downcurrent. Spatial forecasting was used to evaluate the hypothesis that such a deterministic process - rather than randomness or quasiperiodicity - is responsible for the variation between successive ripples. This hypothesis is supported by a forecasting error that increases with forecasting distance, a greater accuracy of nonlinear relative to linear models, and significant differences between forecasts made with the original ripples and those made with surrogate patterns. Forecasting signatures cannot be used to distinguish ripple geometry from sine waves with correlated phase noise, but this kind of structure can be ruled out by two geometric properties of the ripples: Successive ripples are highly

  19. Identification of biomarkers that distinguish chemical contaminants based on gene expression profiles

    PubMed Central

    2014-01-01

    Background High throughput transcriptomics profiles such as those generated using microarrays have been useful in identifying biomarkers for different classification and toxicity prediction purposes. Here, we investigated the use of microarrays to predict chemical toxicants and their possible mechanisms of action. Results In this study, in vitro cultures of primary rat hepatocytes were exposed to 105 chemicals and vehicle controls, representing 14 compound classes. We comprehensively compared various normalization of gene expression profiles, feature selection and classification algorithms for the classification of these 105 chemicals into14 compound classes. We found that normalization had little effect on the averaged classification accuracy. Two support vector machine (SVM) methods, LibSVM and sequential minimal optimization, had better classification performance than other methods. SVM recursive feature selection (SVM-RFE) had the highest overfitting rate when an independent dataset was used for a prediction. Therefore, we developed a new feature selection algorithm called gradient method that had a relatively high training classification as well as prediction accuracy with the lowest overfitting rate of the methods tested. Analysis of biomarkers that distinguished the 14 classes of compounds identified a group of genes principally involved in cell cycle function that were significantly downregulated by metal and inflammatory compounds, but were induced by anti-microbial, cancer related drugs, pesticides, and PXR mediators. Conclusions Our results indicate that using microarrays and a supervised machine learning approach to predict chemical toxicants, their potential toxicity and mechanisms of action is practical and efficient. Choosing the right feature and classification algorithms for this multiple category classification and prediction is critical. PMID:24678894

  20. Impairment and distress patterns distinguishing the melancholic depression subtype: an iSPOT-D report.

    PubMed

    Day, Claire V; John Rush, A; Harris, Anthony W F; Boyce, Philip M; Rekshan, William; Etkin, Amit; DeBattista, Charles; Schatzberg, Alan F; Arnow, Bruce A; Williams, Leanne M

    2015-03-15

    This study seeks to provide a comprehensive and systematic evaluation of baseline clinical and psychological features and treatment response characteristics that differentiate Major Depressive Disorder (MDD) outpatients with and without melancholic features. Reflecting the emphasis in DSM-5, we also include impairment and distress. Participants were assessed pre-treatment on clinical features (severity, risk factors, comorbid conditions, illness course), psychological profile (personality, emotion regulation), functional capacity (social and occupational function, quality of life) and distress/coping (negativity bias, emotional resilience, social skills, satisfaction with life). Participants were randomized to sertraline, escitalopram or venlafaxine extended-release and re-assessed post-treatment at 8 weeks regarding remission, response, and change in impairment and distress. Patients with melancholic features (n=339; 33.7%) were distinguished clinically from non-melancholics by more severe depressive symptoms and greater exposure to abuse in childhood. Psychologically, melancholic patients were defined by introversion, and a greater use of suppression to regulate negative emotion. Melancholics also had poorer capacity for social and occupational function, and physical and psychological quality of life, along with poorer coping, reflected in less emotional resilience and capacity for social skills. Post-treatment, melancholic patients had lower remission and response, but some of this effect was due to the more severe symptoms pre-treatment. The distress/coping outcome measure of capacity for social skills remained significantly lower for melancholic participants. Due to the cross-sectional nature of this study, causal pathways cannot be concluded. Findings provide new insights into a melancholic profile of reduced ability to function interpersonally or effectively deal with one׳s emotions. This distinctly poorer capacity for social skills remained post

  1. Staying and shifting patterns across IGT trials distinguish children with externalizing disorders from controls

    PubMed Central

    Sallum, Isabela; Mata, Fernanda; Miranda, Débora M.; Malloy-Diniz, Leandro F.

    2013-01-01

    The Iowa Gambling Task (IGT) is the most widely instrument used in the assessment of affective decision-making in several populations with frontal impairment. The standard performance measure on the IGT is obtained by calculating the difference between the advantageous and the disadvantageous choices. This standard score does not allows the assessment of the use of different strategies to deal with contingencies of gain and losses across the task. This study aims to compare the standard score method used in IGT with a method that analyses the patterns of staying and shifting among different decks across the 100 choices, considering contingencies of choices with and without losses. We compared the IGT performance of 24 children with externalizing disorders (Attention Deficit Hyperactivity Disorder and Oppositional Defiant Disorder) and 24 healthy age-matched children. The analyses of the standard score across all blocks failed to show differences among children with externalizing disorders and control children. However, healthy children showed a pattern of shifting more from disadvantageous decks to advantageous decks and choosing more consecutive cards from the advantageous decks across all blocks, independently of the contingency of losses. On the other hand, children with externalizing disorders presented a pattern of shifting more from advantageous decks to disadvantageous ones in comparison to healthy children and repeatedly chose cards from the B deck across all blocks. This findings show that even though differences among groups might not be found when using the standard analyses, a different type of analysis might be able to show distinct strategies on the execution of the test. PMID:24348449

  2. Distinguishing the immunostimulatory properties of noncoding RNAs expressed in cancer cells

    PubMed Central

    Tanne, Antoine; Muniz, Luciana R.; Puzio-Kuter, Anna; Leonova, Katerina I.; Gudkov, Andrei V.; Ting, David T.; Monasson, Rémi; Cocco, Simona; Levine, Arnold J.; Bhardwaj, Nina; Greenbaum, Benjamin D.

    2015-01-01

    Recent studies have demonstrated abundant transcription of a set of noncoding RNAs (ncRNAs) preferentially within tumors as opposed to normal tissue. Using an approach from statistical physics, we quantify global transcriptome-wide motif use for the first time, to our knowledge, in human and murine ncRNAs, determining that most have motif use consistent with the coding genome. However, an outlier subset of tumor-associated ncRNAs, typically of recent evolutionary origin, has motif use that is often indicative of pathogen-associated RNA. For instance, we show that the tumor-associated human repeat human satellite repeat II (HSATII) is enriched in motifs containing CpG dinucleotides in AU-rich contexts that most of the human genome and human adapted viruses have evolved to avoid. We demonstrate that a key subset of these ncRNAs functions as immunostimulatory “self-agonists” and directly activates cells of the mononuclear phagocytic system to produce proinflammatory cytokines. These ncRNAs arise from endogenous repetitive elements that are normally silenced, yet are often very highly expressed in cancers. We propose that the innate response in tumors may partially originate from direct interaction of immunogenic ncRNAs expressed in cancer cells with innate pattern recognition receptors, and thereby assign a previously unidentified danger-associated function to a set of dark matter repetitive elements. These findings potentially reconcile several observations concerning the role of ncRNA expression in cancers and their relationship to the tumor microenvironment. PMID:26575629

  3. Arabidopsis gene expression patterns during spaceflight

    NASA Astrophysics Data System (ADS)

    Paul, A.-L.; Ferl, R. J.

    The exposure of Arabidopsis thaliana (Arabidopsis) plants to spaceflight environments resulted in the differential expression of hundreds of genes. A 5 day mission on orbiter Columbia in 1999 (STS-93) carried transgenic Arabidopsis plants engineered with a transgene composed of the alcohol dehydrogenase (Adh) gene promoter linked to the β -Glucuronidase (GUS) reporter gene. The plants were used to evaluate the effects of spaceflight on two fronts. First, expression patterns visualized with the Adh/GUS transgene were used to address specifically the possibility that spaceflight induces a hypoxic stress response, and to assess whether any spaceflight response was similar to control terrestrial hypoxia-induced gene expression patterns. (Paul et al., Plant Physiol. 2001, 126:613). Second, genome-wide patterns of native gene expression were evaluated utilizing the Affymetrix ATH1 GeneChip? array of 8,000 Arabidopsis genes. As a control for the veracity of the array analyses, a selection of genes identified with the arrays was further characterized with quantitative Real-Time RT PCR (ABI - TaqmanTM). Comparison of the patterns of expression for arrays of hybridized with RNA isolated from plants exposed to spaceflight compared to the control arrays revealed hundreds of genes that were differentially expressed in response to spaceflight, yet most genes that are hallmarks of hypoxic stress were unaffected. These results will be discussed in light of current models for plant responses to the spaceflight environment, and with regard to potential future flight opportunities.

  4. Rhythmic alternating patterns of brain activity distinguish rapid eye movement sleep from other states of consciousness

    PubMed Central

    Chow, Ho Ming; Horovitz, Silvina G.; Carr, Walter S.; Picchioni, Dante; Coddington, Nate; Fukunaga, Masaki; Xu, Yisheng; Balkin, Thomas J.; Duyn, Jeff H.; Braun, Allen R.

    2013-01-01

    Rapid eye movement (REM) sleep constitutes a distinct “third state” of consciousness, during which levels of brain activity are commensurate with wakefulness, but conscious awareness is radically transformed. To characterize the temporal and spatial features of this paradoxical state, we examined functional interactions between brain regions using fMRI resting-state connectivity methods. Supporting the view that the functional integrity of the default mode network (DMN) reflects “level of consciousness,” we observed functional uncoupling of the DMN during deep sleep and recoupling during REM sleep (similar to wakefulness). However, unlike either deep sleep or wakefulness, REM was characterized by a more widespread, temporally dynamic interaction between two major brain systems: unimodal sensorimotor areas and the higher-order association cortices (including the DMN), which normally regulate their activity. During REM, these two systems become anticorrelated and fluctuate rhythmically, in reciprocally alternating multisecond epochs with a frequency ranging from 0.1 to 0.01 Hz. This unique spatiotemporal pattern suggests a model for REM sleep that may be consistent with its role in dream formation and memory consolidation. PMID:23733938

  5. Rhythmic alternating patterns of brain activity distinguish rapid eye movement sleep from other states of consciousness.

    PubMed

    Chow, Ho Ming; Horovitz, Silvina G; Carr, Walter S; Picchioni, Dante; Coddington, Nate; Fukunaga, Masaki; Xu, Yisheng; Balkin, Thomas J; Duyn, Jeff H; Braun, Allen R

    2013-06-18

    Rapid eye movement (REM) sleep constitutes a distinct "third state" of consciousness, during which levels of brain activity are commensurate with wakefulness, but conscious awareness is radically transformed. To characterize the temporal and spatial features of this paradoxical state, we examined functional interactions between brain regions using fMRI resting-state connectivity methods. Supporting the view that the functional integrity of the default mode network (DMN) reflects "level of consciousness," we observed functional uncoupling of the DMN during deep sleep and recoupling during REM sleep (similar to wakefulness). However, unlike either deep sleep or wakefulness, REM was characterized by a more widespread, temporally dynamic interaction between two major brain systems: unimodal sensorimotor areas and the higher-order association cortices (including the DMN), which normally regulate their activity. During REM, these two systems become anticorrelated and fluctuate rhythmically, in reciprocally alternating multisecond epochs with a frequency ranging from 0.1 to 0.01 Hz. This unique spatiotemporal pattern suggests a model for REM sleep that may be consistent with its role in dream formation and memory consolidation.

  6. Protein structure protection commits gene expression patterns.

    PubMed

    Chen, Jianping; Liang, Han; Fernández, Ariel

    2008-01-01

    Gene co-expressions often determine module-defining spatial and temporal concurrences of proteins. Yet, little effort has been devoted to tracing coordinating signals for expression correlations to the three-dimensional structures of gene products. We performed a global structure-based analysis of the yeast and human proteomes and contrasted this information against their respective transcriptome organizations obtained from comprehensive microarray data. We show that protein vulnerability quantifies dosage sensitivity for metabolic adaptation phases and tissue-specific patterns of mRNA expression, determining the extent of co-expression similarity of binding partners. The role of protein intrinsic disorder in transcriptome organization is also delineated by interrelating vulnerability, disorder propensity and co-expression patterns. Extremely vulnerable human proteins are shown to be subject to severe post-transcriptional regulation of their expression through significant micro-RNA targeting, making mRNA levels poor surrogates for protein-expression levels. By contrast, in yeast the expression of extremely under-wrapped proteins is likely regulated through protein aggregation. Thus, the 85 most vulnerable proteins in yeast include the five confirmed prions, while in human, the genes encoding extremely vulnerable proteins are predicted to be targeted by microRNAs. Hence, in both vastly different organisms protein vulnerability emerges as a structure-encoded signal for post-transcriptional regulation. Vulnerability of protein structure and the concurrent need to maintain structural integrity are shown to quantify dosage sensitivity, compelling gene expression patterns across tissue types and temporal adaptation phases in a quantifiable manner. Extremely vulnerable proteins impose additional constraints on gene expression: They are subject to high levels of regulation at the post-transcriptional level.

  7. Non-invasive method distinguishes chronic telogen effluvium from mild female pattern hair loss: clinicopathological correlation.

    PubMed

    Bittencourt, Caroline; Teixeira, Fernanda; Ferraro, Daniela A; Soares, Tania C B; Moraes, Aparecida M; Cintra, Maria L

    2016-07-01

    The distinction between chronic telogen effluvium (CTE) and female pattern hair loss (FPHL) is important because of their different prognosis and treatment. Non-invasive methods have been described to be useful in differentiating FPHL from CTE. This prospective study investigated the use of the washing method to differentiate CTE from mild FPHL. Twenty patients with CTE and 17 with FPHL were recruited and followed for 18 months. The diagnosis was established through clinical, laboratory, and histological studies. The patients were asked to abstain from washing their hair for 5 days and then shampoo and collect all hair shed in the process. Hair shafts were then counted and divided into two groups: up to 3 cm in length or longer. In the CTE group, the mean hair count was high (438), and in all cases, <10% were short. In patients with FPHL, the mean count was not as high (215) and in only one patient, short hairs comprised <10% of the total. The greater the number of long hairs, the higher was the density of terminal follicles seen histologically. The CTE group presented a greater number of patients with serum iron values <70 μg/dl. Ferritin levels ranged from 6.98 to 128.33, average of 66.65 (CTE), and 16.5-304.8, average of 114.97 ng/ml (FPHL), but no significant differences were found. The washing test can be useful to avoid biopsy procedures. Iron serum levels are possibly an additional parameter that may improve CTE diagnosis if combined with an earlier test. © 2015 The International Society of Dermatology.

  8. Distinguishing prodromal from first-episode psychosis using neuroanatomical single-subject pattern recognition.

    PubMed

    Borgwardt, Stefan; Koutsouleris, Nikolaos; Aston, Jacqueline; Studerus, Erich; Smieskova, Renata; Riecher-Rössler, Anita; Meisenzahl, Eva M

    2013-09-01

    The at-risk mental state for psychosis (ARMS) and the first episode of psychosis have been associated with structural brain abnormalities that could aid in the individualized early recognition of psychosis. However, it is unknown whether the development of these brain alterations predates the clinical deterioration of at-risk individuals, or alternatively, whether it parallels the transition to psychosis at the single-subject level. We evaluated the performance of an magnetic resonance imaging (MRI)-based classification system in classifying disease stages from at-risk individuals with subsequent transition to psychosis (ARMS-T) and patients with first-episode psychosis (FE). Pairwise and multigroup biomarkers were constructed using the structural MRI data of 22 healthy controls (HC), 16 ARMS-T and 23 FE subjects. The performance of these biomarkers was measured in unseen test cases using repeated nested cross-validation. The classification accuracies in the HC vs FE, HC vs ARMS-T, and ARMS-T vs FE analyses were 86.7%, 80.7%, and 80.0%, respectively. The neuroanatomical decision functions underlying these discriminative results particularly involved the frontotemporal, cingulate, cerebellar, and subcortical brain structures. Our findings suggest that structural brain alterations accumulate at the onset of psychosis and occur even before transition to psychosis allowing for the single-subject differentiation of the prodromal and first-episode stages of the disease. Pattern regression techniques facilitate an accurate prediction of these structural brain dynamics at the early stage of psychosis, potentially allowing for the early recognition of individuals at risk of developing psychosis.

  9. Inferring ultraviolet anatomical exposure patterns while distinguishing the relative contribution of radiation components

    SciTech Connect

    Vuilleumier, Laurent; Milon, Antoine; Vernez, David; Bulliard, Jean-Luc; Moccozet, Laurent

    2013-05-10

    Exposure to solar ultraviolet (UV) radiation is the main causative factor for skin cancer. UV exposure depends on environmental and individual factors, but individual exposure data remain scarce. While ground UV irradiance is monitored via different techniques, it is difficult to translate such observations into human UV exposure or dose because of confounding factors. A multi-disciplinary collaboration developed a model predicting the dose and distribution of UV exposure on the basis of ground irradiation and morphological data. Standard 3D computer graphics techniques were adapted to develop a simulation tool that estimates solar exposure of a virtual manikin depicted as a triangle mesh surface. The amount of solar energy received by various body locations is computed for direct, diffuse and reflected radiation separately. Dosimetric measurements obtained in field conditions were used to assess the model performance. The model predicted exposure to solar UV adequately with a symmetric mean absolute percentage error of 13% and half of the predictions within 17% range of the measurements. Using this tool, solar UV exposure patterns were investigated with respect to the relative contribution of the direct, diffuse and reflected radiation. Exposure doses for various body parts and exposure scenarios of a standing individual were assessed using erythemally-weighted UV ground irradiance data measured in 2009 at Payerne, Switzerland as input. For most anatomical sites, mean daily doses were high (typically 6.2-14.6 Standard Erythemal Dose, SED) and exceeded recommended exposure values. Direct exposure was important during specific periods (e.g. midday during summer), but contributed moderately to the annual dose, ranging from 15 to 24% for vertical and horizontal body parts, respectively. Diffuse irradiation explained about 80% of the cumulative annual exposure dose.

  10. Inferring ultraviolet anatomical exposure patterns while distinguishing the relative contribution of radiation components

    NASA Astrophysics Data System (ADS)

    Vuilleumier, Laurent; Milon, Antoine; Bulliard, Jean-Luc; Moccozet, Laurent; Vernez, David

    2013-05-01

    Exposure to solar ultraviolet (UV) radiation is the main causative factor for skin cancer. UV exposure depends on environmental and individual factors, but individual exposure data remain scarce. While ground UV irradiance is monitored via different techniques, it is difficult to translate such observations into human UV exposure or dose because of confounding factors. A multi-disciplinary collaboration developed a model predicting the dose and distribution of UV exposure on the basis of ground irradiation and morphological data. Standard 3D computer graphics techniques were adapted to develop a simulation tool that estimates solar exposure of a virtual manikin depicted as a triangle mesh surface. The amount of solar energy received by various body locations is computed for direct, diffuse and reflected radiation separately. Dosimetric measurements obtained in field conditions were used to assess the model performance. The model predicted exposure to solar UV adequately with a symmetric mean absolute percentage error of 13% and half of the predictions within 17% range of the measurements. Using this tool, solar UV exposure patterns were investigated with respect to the relative contribution of the direct, diffuse and reflected radiation. Exposure doses for various body parts and exposure scenarios of a standing individual were assessed using erythemally-weighted UV ground irradiance data measured in 2009 at Payerne, Switzerland as input. For most anatomical sites, mean daily doses were high (typically 6.2-14.6 Standard Erythemal Dose, SED) and exceeded recommended exposure values. Direct exposure was important during specific periods (e.g. midday during summer), but contributed moderately to the annual dose, ranging from 15 to 24% for vertical and horizontal body parts, respectively. Diffuse irradiation explained about 80% of the cumulative annual exposure dose.

  11. Prelinguistic Pitch Patterns Expressing "Communication" and "Apprehension"

    ERIC Educational Resources Information Center

    Papaeliou, Christina F.; Trevarthen, Colwyn

    2006-01-01

    This study examined whether pitch patterns of prelinguistic vocalizations could discriminate between social vocalizations, uttered apparently with the intention to communicate, and "private" speech, related to solitary activities as an expression of "thinking". Four healthy ten month old English-speaking infants (2 boys and 2 girls) were…

  12. Expression of TRAF1 and nuclear c-Rel distinguishes primary mediastinal large cell lymphoma from other types of diffuse large B-cell lymphoma.

    PubMed

    Rodig, Scott J; Savage, Kerry J; LaCasce, Ann S; Weng, Andrew P; Harris, Nancy L; Shipp, Margaret A; Hsi, Eric D; Gascoyne, Randy D; Kutok, Jeffery L

    2007-01-01

    Primary mediastinal large B-cell lymphoma (PMLBCL) is a recently identified subtype of diffuse large B-cell lymphoma (DLBCL) that is difficult to distinguish from other types of DLBCL on the basis of histologic features alone. We recently identified a molecular signature of PMLBCL that is distinct from other forms of DLBCL but shares features with classical Hodgkin lymphoma. This signature includes activation of the nuclear factor kappaB (NFkappaB) signaling pathway, which in part, acts through nuclear translocation of c-Rel containing NFkappaB transcriptional complexes, and subsequent expression of NFkappaB target genes such as tumor necrosis factor receptor-associated factor-1 (TRAF1). Using standard immunohistochemical techniques, we examined 251 large B-cell lymphomas (78 cases of PMLBCL and 173 cases of other types of DLBCL) to determine whether the expression patterns of c-Rel and TRAF1 could reliably distinguish between PMLBCL and other types of DLBCL. Robust nuclear c-Rel was present in 31 of 48 (65%) cases of PMLBCL and 28 of 160 (18%) cases of DLBCL. In addition, cytoplasmic TRAF1 expression was seen in 48 of 78 (62%) cases of PMLBCL, but only 20 of 173 (12%) cases of DLBCL. Finally, the combined expression of nuclear c-Rel and TRAF1 was seen in 24 of 45 cases (53%) of PMLBCL, but in only 3 of 156 cases (2%) of other types of DLBCL. Thus, the combined nuclear localization of c-Rel and the cellular expression of TRAF1 is a highly specific (specificity=98%) means to distinguish PMLBCL from DLBCL that is readily applicable to routine surgical pathology practice.

  13. Recognition memory strength is predicted by pupillary responses at encoding while fixation patterns distinguish recollection from familiarity.

    PubMed

    Kafkas, Alexandros; Montaldi, Daniela

    2011-10-01

    Thirty-five healthy participants incidentally encoded a set of man-made and natural object pictures, while their pupil response and eye movements were recorded. At retrieval, studied and new stimuli were rated as novel, familiar (strong, moderate, or weak), or recollected. We found that both pupil response and fixation patterns at encoding predict later recognition memory strength. The extent of pupillary response accompanying incidental encoding was found to be predictive of subsequent memory. In addition, the number of fixations was also predictive of later recognition memory strength, suggesting that the accumulation of greater visual detail, even for single objects, is critical for the creation of a strong memory. Moreover, fixation patterns at encoding distinguished between recollection and familiarity at retrieval, with more dispersed fixations predicting familiarity and more clustered fixations predicting recollection. These data reveal close links between the autonomic control of pupil responses and eye movement patterns on the one hand and memory encoding on the other. Moreover, the data illustrate quantitative as well as qualitative differences in the incidental visual processing of stimuli, which are differentially predictive of the strength and the kind of memory experienced at recognition.

  14. Empathic Exchanges in Online Cancer Support Groups: Distinguishing Message Expression and Reception Effects

    PubMed Central

    Han, Jeong Yeob; Shah, Dhavan V.; Kim, Eunkyung; Namkoong, Kang; Lee, Sun-Young; Moon, Tae Joon; Cleland, Rich; Bu, Q. Lisa; McTavish, Fiona M.; Gustafson, David H.

    2013-01-01

    Past studies on the efficacy of participation in online cancer support groups have primarily focused on the role of expression in the accrual of health benefits for participants. Unfortunately, few steps have been taken to determine whether this observed effect arises solely from the internal mental processes underlying the act of expressing or, perhaps, owes something to a nuanced, multidimensional understanding of expression that includes reception of responses to what is expressed. To test for the multilayered effect, we attend to one of the key concepts in the online support community scholarship: empathy. Our findings suggest that it is a combination of empathy expression and reception that is crucial to attaining optimal benefits for cancer patients. Further, our finding supports the buffering hypothesis that empathic expression provides a salutary effect for patients who experienced a higher degree of concern associated with their cancer diagnosis and follow-up treatments. PMID:21318917

  15. Characterizing noise structure in single-cell RNA-seq distinguishes genuine from technical stochastic allelic expression.

    PubMed

    Kim, Jong Kyoung; Kolodziejczyk, Aleksandra A; Ilicic, Tomislav; Illicic, Tomislav; Teichmann, Sarah A; Marioni, John C

    2015-10-22

    Single-cell RNA-sequencing (scRNA-seq) facilitates identification of new cell types and gene regulatory networks as well as dissection of the kinetics of gene expression and patterns of allele-specific expression. However, to facilitate such analyses, separating biological variability from the high level of technical noise that affects scRNA-seq protocols is vital. Here we describe and validate a generative statistical model that accurately quantifies technical noise with the help of external RNA spike-ins. Applying our approach to investigate stochastic allele-specific expression in individual cells, we demonstrate that a large fraction of stochastic allele-specific expression can be explained by technical noise, especially for lowly and moderately expressed genes: we predict that only 17.8% of stochastic allele-specific expression patterns are attributable to biological noise with the remainder due to technical noise.

  16. Characterizing noise structure in single-cell RNA-seq distinguishes genuine from technical stochastic allelic expression

    PubMed Central

    Kim, Jong Kyoung; Kolodziejczyk, Aleksandra A.; Illicic, Tomislav; Teichmann, Sarah A.; Marioni, John C.

    2015-01-01

    Single-cell RNA-sequencing (scRNA-seq) facilitates identification of new cell types and gene regulatory networks as well as dissection of the kinetics of gene expression and patterns of allele-specific expression. However, to facilitate such analyses, separating biological variability from the high level of technical noise that affects scRNA-seq protocols is vital. Here we describe and validate a generative statistical model that accurately quantifies technical noise with the help of external RNA spike-ins. Applying our approach to investigate stochastic allele-specific expression in individual cells, we demonstrate that a large fraction of stochastic allele-specific expression can be explained by technical noise, especially for lowly and moderately expressed genes: we predict that only 17.8% of stochastic allele-specific expression patterns are attributable to biological noise with the remainder due to technical noise. PMID:26489834

  17. Claudin 6 expression is useful to distinguish myxofibrosarcomas from other myxoid soft tissue tumors.

    PubMed

    Bekki, Hirofumi; Yamamoto, Hidetaka; Takizawa, Katsumi; Iwasaki, Takeshi; Otsuka, Hiroshi; Yamada, Yuichi; Kohashi, Kenichi; Harimaya, Katsumi; Iwamoto, Yukihide; Oda, Yoshinao

    2017-06-01

    Myxofibrosarcoma (MFS) is characterized by abundant myxoid stroma, a wide spectrum of cytological atypia, and frequent local recurrence. Some soft tissue tumors with myxoid stroma can histologically mimic MFS, but have different biological behaviors. Here we sought to identify a useful diagnostic marker for MFS. After our analysis of the gene expression dataset from the Gene Expression Omnibus database, we focused on claudin 6 (CLDN 6). The status of CLDN 6 was assessed by immunohistochemistry in 61 samples of MFS and other (benign) myxoid soft tissue tumors (28 myxoma samples, 12 nodular fasciitis samples), 18 low-grade fibromyxoid sarcoma, 30 myxoid liposarcoma, 29 extraskeletal myxoid chondrosarcoma and 27 dedifferentiated liposarcoma with myxoid feature samples. The correlation between the expression of CLDN 6 and clinicopathological findings in MFS was also investigated. Immunohistochemically, high expression of CLDN 6 was observed in approx. 65% of the MFSs, whereas the benign soft tissue tumors did not show a high expression of CLDN 6. The expression of CLDN 6 in the MFS was significantly higher than those of other tumor specimens. Among the MFSs, the high expression of CLDN 6 was correlated with high FNCLCC grades and high AJCC stages. CLDN 6 may be useful for the differential diagnosis from benign myxoid tumor and for predicting the aggressive biological behavior of MFS. Copyright © 2016 Elsevier GmbH. All rights reserved.

  18. N-cadherin expression level distinguishes reserved versus primed states of hematopoietic stem cells.

    PubMed

    Haug, Jeffrey S; He, Xi C; Grindley, Justin C; Wunderlich, Joshua P; Gaudenz, Karin; Ross, Jason T; Paulson, Ariel; Wagner, Kathryn P; Xie, Yucai; Zhu, Ruihong; Yin, Tong; Perry, John M; Hembree, Mark J; Redenbaugh, Erin P; Radice, Glenn L; Seidel, Christopher; Li, Linheng

    2008-04-10

    Osteoblasts expressing the homophilic adhesion molecule N-cadherin form a hematopoietic stem cell (HSC) niche. Therefore, we examined how N-cadherin expression in HSCs relates to their function. We found that bone marrow (BM) cells highly expressing N-cadherin (N-cadherin(hi)) are not stem cells, being largely devoid of a Lineage(-)Sca1(+)cKit(+) population and unable to reconstitute hematopoietic lineages in irradiated recipient mice. Instead, long-term HSCs form distinct populations expressing N-cadherin at intermediate (N-cadherin(int)) or low (N-cadherin(lo)) levels. The minority N-cadherin(lo) population can robustly reconstitute the hematopoietic system, express genes that may prime them to mobilize, and predominate among HSCs mobilized from BM to spleen. The larger N-cadherin(int) population performs poorly in reconstitution assays when freshly isolated but improves in response to overnight in vitro culture. Their expression profile and lower cell-cycle entry rate suggest N-cadherin(int) cells are being held in reserve. Thus, differential N-cadherin expression reflects functional distinctions between two HSC subpopulations.

  19. Systemic and cell type-specific gene expression patterns in scleroderma skin

    PubMed Central

    Whitfield, Michael L.; Finlay, Deborah R.; Murray, John Isaac; Troyanskaya, Olga G.; Chi, Jen-Tsan; Pergamenschikov, Alexander; McCalmont, Timothy H.; Brown, Patrick O.; Botstein, David; Connolly, M. Kari

    2003-01-01

    We used DNA microarrays representing >12,000 human genes to characterize gene expression patterns in skin biopsies from individuals with a diagnosis of systemic sclerosis with diffuse scleroderma. We found consistent differences in the patterns of gene expression between skin biopsies from individuals with scleroderma and those from normal, unaffected individuals. The biopsies from affected individuals showed nearly indistinguishable patterns of gene expression in clinically affected and clinically unaffected tissue, even though these were clearly distinguishable from the patterns found in similar tissue from unaffected individuals. Genes characteristically expressed in endothelial cells, B lymphocytes, and fibroblasts showed differential expression between scleroderma and normal biopsies. Analysis of lymphocyte populations in scleroderma skin biopsies by immunohistochemistry suggest the B lymphocyte signature observed on our arrays is from CD20+ B cells. These results provide evidence that scleroderma has systemic manifestations that affect multiple cell types and suggests genes that could be used as potential markers for the disease. PMID:14530402

  20. Differential IgM expression distinguishes two types of pediatric Burkitt lymphoma in mouse and human

    PubMed Central

    Eason, Anthony B.; Sin, Sang-Hoon; Lin, Carolina; Damania, Blossom; Park, Steven; Fedoriw, Yuri; Bacchi, Carlos E.; Dittmer, Dirk P.

    2016-01-01

    Endemic Burkitt lymphoma (eBL) is primarily a childhood cancer in parts of Africa and Brazil. Classic studies describe eBL as a homogeneous entity based on t(8;14) IgH-Myc translocation and clinical response to cytotoxic therapy. By contrast, sporadic BL (sBL) in Western countries is considered more heterogeneous, and affects both children and adults. It is overrepresented in AIDS patients. Unlike diffuse large B cell lymphoma (DLBCL), molecular subtypes within BL have not been well defined. We find that differential IgM positivity can be used to describe two subtypes of pediatric Burkitt lymphoma both in a high incidence region (Brazil), as well as in a sporadic region (US), suggesting the phenotype is not necessarily geographically isolated. Moreover, we find that IgM positivity also distinguishes between early and late onset BL in the standard Eμ-Myc mouse model of BL. This suggests that the t(8;14) translocation not only can take place before, but also after isotype switch recombination, and that IgM-negative, t(8;14) positive lymphomas in children should nevertheless be considered BL. PMID:27566574

  1. Distinguishing the time course of lexical and discourse processes through context, coreference, and quantified expressions.

    PubMed

    Huang, Yi Ting; Gordon, Peter C

    2011-07-01

    How does prior context influence lexical and discourse-level processing during real-time language comprehension? Experiment 1 examined whether the referential ambiguity introduced by a repeated, anaphoric expression had an immediate or delayed effect on lexical and discourse processing, using an eye-tracking-while-reading task. Eye movements indicated facilitated recognition of repeated expressions, suggesting that prior context can rapidly influence lexical processing. However, context effects at the discourse level affected later processing, appearing in longer regression-path durations 2 words after the anaphor and in greater rereading times of the antecedent expression. Experiments 2 and 3 explored the nature of this delay by examining the role of the preceding context in activating relevant representations. Offline and online interpretations confirmed that relevant referents were activated following the critical context. Nevertheless, their initial unavailability during comprehension suggests a robust temporal division between lexical and discourse-level processing.

  2. Gene expression analysis distinguishes tissue specific and gender related functions among adult Ascaris suum tissues

    PubMed Central

    Wang, Zhengyuan; Gao, Xin; Martin, John; Yin, Yong; Abubucker, Sahar; Rash, Amy C.; Li, Ben-Wen; Nash, Bill; Hallsworth-Pepin, Kym; Jasmer, Douglas P.; Mitreva, Makedonka

    2013-01-01

    Over a billion people are infected by Ascaris spp. intestinal parasites. To clarify functional differences among tissues of adult A. suum, we compared gene expression by various tissues of these worms by expression microarray methods.. The A. suum genome was sequenced and assembled to allow generation of microarray elements. Expression of over 40,000 60-mer elements was investigated in a variety of tissues from both male and female adult worms. Nearly 50 percent of the elements for which signal was detected exhibited differential expression among different tissues. The unique profile of transcripts identified for each tissue clarified functional distinctions among tissues, such as chitin binding in the ovary and peptidase activity in the intestines. Interestingly, hundreds of gender-specific elements were characterized in multiple non-reproductive tissues of female or male worms, with most prominence of gender differences in intestinal tissue. A. suum genes from the same family were frequently expressed differently among tissues. Transcript abundance for genes specific to A. suum, by comparison to Caenorhabditis elegans, varied to a greater extent among tissues than for genes conserved between A. suum and C. elegans. Analysis using C. elegans protein interaction data identified functional modules conserved between these two nematodes, resulting in identification of functional predictions of essential subnetworks of protein interactions and how these networks may vary among nematode tissues. A notable finding was very high module similarity between adult reproductive tissues and intestine. Our results provide the most comprehensive assessment of gene expression among tissues of a parasitic nematode to date. PMID:23572074

  3. Distinct phases in the positive selection of CD8+ T cells distinguished by intrathymic migration and T-cell receptor signaling patterns

    PubMed Central

    Ross, Jenny O.; Melichar, Heather J.; Au-Yeung, Byron B.; Herzmark, Paul; Weiss, Arthur; Robey, Ellen A.

    2014-01-01

    Positive selection of CD8 T cells in the thymus is thought to be a multistep process lasting 3–4 d; however, the discrete steps involved are poorly understood. Here, we examine phenotypic changes, calcium signaling, and intrathymic migration in a synchronized cohort of MHC class I-specific thymocytes undergoing positive selection in situ. Transient elevations in intracellular calcium concentration ([Ca2+]i) and migratory pauses occurred throughout the first 24 h of positive selection, becoming progressively briefer and accompanied by a gradual shift in basal [Ca2+]i over time. Changes in chemokine-receptor expression and relocalization from the cortex to medulla occurred between 12 and 24 h after the initial encounter with positive-selecting ligands, a time frame at which the majority of thymocytes retain CD4 and CD8 expression and still require T-cell receptor (TCR) signaling to efficiently complete positive selection. Our results identify distinct phases in the positive selection of MHC class I-specific thymocytes that are distinguished by their TCR-signaling pattern and intrathymic location and provide a framework for understanding the multistep process of positive selection in the thymus. PMID:24927565

  4. Distinguishing the Time Course of Lexical and Discourse Processes through Context, Coreference, and Quantified Expressions

    ERIC Educational Resources Information Center

    Huang, Yi Ting; Gordon, Peter C.

    2011-01-01

    How does prior context influence lexical and discourse-level processing during real-time language comprehension? Experiment 1 examined whether the referential ambiguity introduced by a repeated, anaphoric expression had an immediate or delayed effect on lexical and discourse processing, using an eye-tracking-while-reading task. Eye movements…

  5. Major histocompatibility complex class II expression distinguishes two distinct B cell developmental pathways during ontogeny

    PubMed Central

    1994-01-01

    All mature B cells coexpress major histocompatibility complex (MHC) class II molecules, I-A and I-E, which are restriction elements required for antigen presentation to CD4+ T cells. However, the expression of class II during the early stages of B cell development has been unclear. We demonstrate here that there is a difference in the expression of class II during murine B cell development in the fetal liver and adult bone marrow (BM). These differences define two distinct B cell developmental pathways. The Fetal-type (FT) pathway is characterized by pre-B and immature IgM+ B cells generated in the fetal liver which initially lack all class II expression. In contrast, the Adult-type (AT) pathway is typified by B cells developing in the adult BM which express class II molecules from the pre-B cell stage. In vitro stromal cell cultures of sorted fetal liver and adult BM pro-B cells indicated that the difference in I-A expression during B cell development is intrinsic to the progenitors. In addition, we show that FT B cell development is not restricted to the fetal liver but occurs in the peritoneal cavities, spleens, liver, and BM of young mice up to at least 1 mo of age. The AT B cell development begins to emerge after birth but is, however, restricted to the BM environment. These findings indicate that there are two distinct B cell developmental pathways during ontogeny, each of which could contribute differentially to the immune repertoire and thus the functions of B cell subsets and lineages. PMID:7913950

  6. K(+) channel expression distinguishes subpopulations of parvalbumin- and somatostatin-containing neocortical interneurons.

    PubMed

    Chow, A; Erisir, A; Farb, C; Nadal, M S; Ozaita, A; Lau, D; Welker, E; Rudy, B

    1999-11-01

    Kv3.1 and Kv3.2 K(+) channel proteins form similar voltage-gated K(+) channels with unusual properties, including fast activation at voltages positive to -10 mV and very fast deactivation rates. These properties are thought to facilitate sustained high-frequency firing. Kv3.1 subunits are specifically found in fast-spiking, parvalbumin (PV)-containing cortical interneurons, and recent studies have provided support for a crucial role in the generation of the fast-spiking phenotype. Kv3.2 mRNAs are also found in a small subset of neocortical neurons, although the distribution of these neurons is different. We raised antibodies directed against Kv3.2 proteins and used dual-labeling methods to identify the neocortical neurons expressing Kv3.2 proteins and to determine their subcellular localization. Kv3.2 proteins are prominently expressed in patches in somatic and proximal dendritic membrane as well as in axons and presynaptic terminals of GABAergic interneurons. Kv3.2 subunits are found in all PV-containing neurons in deep cortical layers where they probably form heteromultimeric channels with Kv3.1 subunits. In contrast, in superficial layer PV-positive neurons Kv3.2 immunoreactivity is low, but Kv3.1 is still prominently expressed. Because Kv3.1 and Kv3.2 channels are differentially modulated by protein kinases, these results raise the possibility that the fast-spiking properties of superficial- and deep-layer PV neurons are differentially regulated by neuromodulators. Interestingly, Kv3. 2 but not Kv3.1 proteins are also prominent in a subset of seemingly non-fast-spiking, somatostatin- and calbindin-containing interneurons, suggesting that the Kv3.1-Kv3.2 current type can have functions other than facilitating high-frequency firing.

  7. Expression of Dbx1, Neurogenin 2, Semaphorin 5A, Cadherin 8, and Emx1 distinguish ventral and lateral pallial histogenetic divisions in the developing mouse claustroamygdaloid complex.

    PubMed

    Medina, Loreta; Legaz, Isabel; González, Gertrudis; De Castro, Fernando; Rubenstein, John L R; Puelles, Luis

    2004-07-05

    We studied the lateral and ventral pallial divisions of the claustroamygdaloid complex by means of analysis of expression patterns of the developmental regulatory genes Tbr1, Dbx1, Neurogenin 2, Emx1, Cadherin 8, and Semaphorin 5A in mouse developing telencephalon, from embryonic day 12.5 until birth. Our results indicate that these genes help to distinguish distinct lateral and ventral pallial histogenetic divisions in the embryonic telencephalon. Tbr1 is broadly expressed in both lateral and ventral pallial histogenetic divisions (the lateroventral migratory stream plus the mantle) during early and intermediate embryonic development; its signal becomes weak in parts of the mantle during late embryonic development. Dbx1 is strongly and specifically expressed in progenitor cells (ventricular zone) of the ventral pallium during early embryonic development, but there is no signal of this gene in the rest of the pallium nor the subpallium. Neurogenin 2 and Semaphorin 5A are both expressed in a ventral subdivision of the lateroventral migratory stream (called by us the ventral migratory stream). Further, specific nuclei of the claustral complex and pallial amygdala show strong expression of Neurogenin 2 and/or Semaphorin 5A, including the ventromedial claustrum and endopiriform nuclei, the lateral and basomedial amygdalar nuclei, the anterior and posteromedial cortical amygdalar areas, plus the amygdalo-hippocampal area. We interpret these nuclei or areas of the claustroamygdaloid complex as possible derivatives of the ventral pallium. In contrast, during embryonic development the dorsolateral claustrum, the basolateral amygdalar nucleus, and the posterolateral cortical amygdalar area do not express or show weak expression of Neurogenin 2 or Semaphorin 5A, but express selectively and strongly Cadherin 8 plus Emx1, and may be derivatives of the lateral pallium. The lateral pallial and ventral pallial divisions of the claustroamygdaloid complex appear to have some

  8. Identification and intensity of disgust: Distinguishing visual, linguistic and facial expressions processing in Parkinson disease.

    PubMed

    Sedda, Anna; Petito, Sara; Guarino, Maria; Stracciari, Andrea

    2017-07-14

    Most of the studies since now show an impairment for facial displays of disgust recognition in Parkinson disease. A general impairment in disgust processing in patients with Parkinson disease might adversely affect their social interactions, given the relevance of this emotion for human relations. However, despite the importance of faces, disgust is also expressed through other format of visual stimuli such as sentences and visual images. The aim of our study was to explore disgust processing in a sample of patients affected by Parkinson disease, by means of various tests tackling not only facial recognition but also other format of visual stimuli through which disgust can be recognized. Our results confirm that patients are impaired in recognizing facial displays of disgust. Further analyses show that patients are also impaired and slower for other facial expressions, with the only exception of happiness. Notably however, patients with Parkinson disease processed visual images and sentences as controls. Our findings show a dissociation within different formats of visual stimuli of disgust, suggesting that Parkinson disease is not characterized by a general compromising of disgust processing, as often suggested. The involvement of the basal ganglia-frontal cortex system might spare some cognitive components of emotional processing, related to memory and culture, at least for disgust. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Mucosal Expression of Type 2 and Type 17 Immune Response Genes Distinguishes Ulcerative Colitis From Colon-Only Crohn's Disease in Treatment-Naive Pediatric Patients.

    PubMed

    Rosen, Michael J; Karns, Rebekah; Vallance, Jefferson E; Bezold, Ramona; Waddell, Amanda; Collins, Margaret H; Haberman, Yael; Minar, Phillip; Baldassano, Robert N; Hyams, Jeffrey S; Baker, Susan S; Kellermayer, Richard; Noe, Joshua D; Griffiths, Anne M; Rosh, Joel R; Crandall, Wallace V; Heyman, Melvin B; Mack, David R; Kappelman, Michael D; Markowitz, James; Moulton, Dedrick E; Leleiko, Neal S; Walters, Thomas D; Kugathasan, Subra; Wilson, Keith T; Hogan, Simon P; Denson, Lee A

    2017-05-01

    There is controversy regarding the role of the type 2 immune response in the pathogenesis of ulcerative colitis (UC)-few data are available from treatment-naive patients. We investigated whether genes associated with a type 2 immune response in the intestinal mucosa are up-regulated in treatment-naive pediatric patients with UC compared with patients with Crohn's disease (CD)-associated colitis or without inflammatory bowel disease (IBD), and whether expression levels are associated with clinical outcomes. We used a real-time reverse-transcription quantitative polymerase chain reaction array to analyze messenger RNA (mRNA) expression patterns in rectal mucosal samples from 138 treatment-naive pediatric patients with IBD and macroscopic rectal disease, as well as those from 49 children without IBD (controls), enrolled in a multicenter prospective observational study from 2008 to 2012. Results were validated in real-time reverse-transcription quantitative polymerase chain reaction analyses of rectal RNA from an independent cohort of 34 pediatric patients with IBD and macroscopic rectal disease and 17 controls from Cincinnati Children's Hospital Medical Center. We measured significant increases in mRNAs associated with a type 2 immune response (interleukin [IL]5 gene, IL13, and IL13RA2) and a type 17 immune response (IL17A and IL23) in mucosal samples from patients with UC compared with patients with colon-only CD. In a regression model, increased expression of IL5 and IL17A mRNAs distinguished patients with UC from patients with colon-only CD (P = .001; area under the receiver operating characteristic curve, 0.72). We identified a gene expression pattern in rectal tissues of patients with UC, characterized by detection of IL13 mRNA, that predicted clinical response to therapy after 6 months (odds ratio [OR], 6.469; 95% confidence interval [CI], 1.553-26.94), clinical response after 12 months (OR, 6.125; 95% CI, 1.330-28.22), and remission after 12 months (OR, 5

  10. Expression Profiles of miRNA Subsets Distinguish Human Colorectal Carcinoma and Normal Colonic Mucosa

    PubMed Central

    Pellatt, Daniel F; Stevens, John R; Wolff, Roger K; Mullany, Lila E; Herrick, Jennifer S; Samowitz, Wade; Slattery, Martha L

    2016-01-01

    OBJECTIVES: MicroRNAs (miRNAs) are small, non-protein-coding RNA molecules that are commonly dysregulated in colorectal tumors. The objective of this study was to identify smaller subsets of highly predictive miRNAs. METHODS: Data come from population-based studies of colorectal cancer conducted in Utah and the Kaiser Permanente Medical Care Program. Tissue samples were available for 1,953 individuals, of which 1,894 had carcinoma tissue and 1,599 had normal mucosa available for statistical analysis. Agilent Human miRNA Microarray V.19.0 was used to generate miRNA expression profiles; validation of expression levels was carried out using quantitative PCR. We used random forest analysis and verified findings with logistic modeling in separate data sets. Important microRNAs are identified and bioinformatics tools are used to identify target genes and related biological pathways. RESULTS: We identified 16 miRNAs for colon and 17 miRNAs for rectal carcinoma that appear to differentiate between carcinoma and normal mucosa; of these, 12 were important for both colon and rectal cancer, hsa-miR-663b, hsa-miR-4539, hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-4506, hsa-miR-92a-3p, hsa-miR-93-5p, hsa-miR-145-5p, hsa-miR-3651, hsa-miR-378a-3p, and hsa-miR-378i. Estimated misclassification rates were low at 4.83% and 2.5% among colon and rectal observations, respectively. Among independent observations, logistic modeling reinforced the importance of these miRNAs, finding the primary principal components of their variation statistically significant (P<0.001 among both colon and rectal observations) and again producing low misclassification rates. Repeating our analysis without those miRNAs initially identified as important identified other important miRNAs; however, misclassification rates increased and distinctions between remaining miRNAs in terms of classification importance were reduced. CONCLUSIONS: Our data support the hypothesis that while many miRNAs are

  11. Towards a multi protein and mRNA expression of biological predictive and distinguish model for post stroke depression

    PubMed Central

    Yue, Yingying; Jiang, Haitang; Liu, Rui; Yin, Yingying; Zhang, Yuqun; Liang, Jinfeng; Li, Shenghua; Wang, Jun; Lu, Jianxin; Geng, Deqin; Wu, Aiqin; Yuan, Yonggui

    2016-01-01

    Previous studies suggest that neurotrophic factors participate in the development of stroke and depression. So we investigated the utility of these biomarkers as predictive and distinguish model for post stroke depression (PSD). 159 individuals including PSD, stroke without depression (Non-PSD), major depressive disorder (MDD) and normal control groups were recruited and examined the protein and mRNA expression levels of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptors (VEGFR2), placental growth factor (PIGF), insulin-like growth factor (IGF-1) and insulin-like growth factor receptors (IGF-1R). The chi-square test was used to evaluate categorical variable, while nonparametric test and one-way analysis of variance were applied to continuous variables of general characteristics, clinical and biological changes. In order to explore the predictive and distinguish role of these factors in PSD, discriminant analysis and receiver operating characteristic curve were calculated. The four groups had statistical differences in these neurotrophic factors (all P < 0.05) except VEGF concentration and IGF-1R mRNA (P = 0.776, P = 0.102 respectively). We identified these mRNA expression and protein analytes with general predictive performance for PSD and Non-PSD groups [area under the curve (AUC): 0.805, 95% CI, 0.704-0.907, P < 0.001]. Importantly, there is an excellent predictive performance (AUC: 0.984, 95% CI, 0.964-1.000, P < 0.001) to differentiate PSD patients from MDD patients. This was the first study to explore the changes of neurotrophic factors family in PSD patients, the results intriguingly demonstrated that the combination of protein and mRNA expression of biological factors could use as a predictive and discriminant model for PSD. PMID:27527872

  12. Chemokine-like receptor 1 expression and chemerin-directed chemotaxis distinguish plasmacytoid from myeloid dendritic cells in human blood.

    PubMed

    Zabel, Brian A; Silverio, Amanda M; Butcher, Eugene C

    2005-01-01

    Plasmacytoid dendritic cells (pDCs) are versatile cells of the immune response, secreting type I IFNs and differentiating into potent immunogenic or tolerogenic APCs. pDCs can express adhesion and chemokine receptors for lymphoid tissues, but are also recruited by unknown mechanisms during tissue inflammation. We use a novel mAb specific for serpentine chemokine-like receptor 1 (CMKLR1) to evaluate its expression by circulating leukocytes in humans. We show that CMKLR1 is expressed by circulating pDCs in human blood, whereas myeloid DCs (mDCs) as well as lymphocytes, monocytes, neutrophils, and eosinophils are negative. We identify a major serum agonist activity for CMKLR1 as chemerin, a proteolytically activated attractant and the sole known ligand for CMKLR1, and we show that chemerin is activated during blood coagulation and attracts pDC but not mDC in ex vivo chemotaxis assays. We conclude that CMKLR1 expression and chemerin-mediated chemotaxis distinguish circulating pDCs from mDCs, providing a potential mechanism for their differential contribution to or regulation of immune responses at sites of bleeding or inflammatory protease activity.

  13. Distinguishing benign from malignant mesothelial cells in effusions by Glut-1, EMA, and Desmin expression: an evidence-based approach.

    PubMed

    Kuperman, Michael; Florence, Roxanne R; Pantanowitz, Liron; Visintainer, Paul F; Cibas, Edmund S; Otis, Christopher N

    2013-02-01

    Distinguishing malignant mesothelioma (MM) from reactive mesothelial hyperplasia (RM) may be difficult in effusions. This study tested the hypothesis that immunocytochemistry (IC) in effusion cell blocks (CB) can distinguish MM from RM and that the results may be applied to individual specimens. External validation of a risk score (RS) model associating sensitivity and specificity was applied to an external set of MM and RM specimens from a separate institution. Forty three effusion cytology CBs of 25 confirmed malignant mesotheliomas were compared to CBs of 23 benign mesothelial effusions without inflammation and 13 reactive mesothelial proliferations associated with inflammation. Glut-1, EMA, and Desmin expression were evaluated by immunocytochemistry on CBs. Each antibody was compared using ROC values, where the area under the curve (AUC) was 0.90, 0.82, and 0.84 for Glut-1, EMA, and Desmin, respectively. Logistic regression (LR) analysis was applied to a combination of Glut-1 and EMA. A combined ROC curve was modeled for Glut-1 and EMA (AUC = 0.93). A RS = 2 × (Glut-1%) + 1 × (EMA%) was created from this ROC curve. When applied to an external set of MM and RM, the RS resulted in an ROC with AUC = 0.91. In conclusion, a RS derived from a LR of Glut-1 and EMA IC greatly improves the distinction between MM from RM cells in individual effusions. The study illustrates principles of evidence-based pathology concerning internal and external test performance in the differential diagnosis of MM versus RM.

  14. Differential gene expression from microarray analysis distinguishes woven and lamellar bone formation in the rat ulna following mechanical loading.

    PubMed

    McKenzie, Jennifer A; Bixby, Elise C; Silva, Matthew J

    2011-01-01

    Formation of woven and lamellar bone in the adult skeleton can be induced through mechanical loading. Although much is known about the morphological appearance and structural properties of the newly formed bone, the molecular responses to loading are still not well understood. The objective of our study was to use a microarray to distinguish the molecular responses between woven and lamellar bone formation induced through mechanical loading. Rat forelimb loading was completed in a single bout to induce the formation of woven bone (WBF loading) or lamellar bone (LBF loading). A set of normal (non-loaded) rats were used as controls. Microarrays were performed at three timepoints after loading: 1 hr, 1 day and 3 days. Confirmation of microarray results was done for a select group of genes using quantitative real-time PCR (qRT-PCR). The micorarray identified numerous genes and pathways that were differentially regulated for woven, but not lamellar bone formation. Few changes in gene expression were evident comparing lamellar bone formation to normal controls. A total of 395 genes were differentially expressed between formation of woven and lamellar bone 1 hr after loading, while 5883 and 5974 genes were differentially expressed on days 1 and 3, respectively. Results suggest that not only are the levels of expression different for each type of bone formation, but that distinct pathways are activated only for woven bone formation. A strong early inflammatory response preceded an increase in angiogenic and osteogenic gene expression for woven bone formation. Furthermore, at later timepoints there was evidence of bone resorption after WBF loading. In summary, the vast coverage of the microarray offers a comprehensive characterization of the early differences in expression between woven and lamellar bone formation.

  15. Expression patterns reveal niche diversification in a marine microbial assemblage

    PubMed Central

    Gifford, Scott M; Sharma, Shalabh; Booth, Melissa; Moran, Mary Ann

    2013-01-01

    Resolving the ecological niches of coexisting marine microbial taxa is challenging due to the high species richness of microbial communities and the apparent functional redundancy in bacterial genomes and metagenomes. Here, we generated over 11 million Illumina reads of protein-encoding transcripts collected from well-mixed southeastern US coastal waters to characterize gene expression patterns distinguishing the ecological roles of hundreds of microbial taxa sharing the same environment. The taxa with highest in situ growth rates (based on relative abundance of ribosomal protein transcripts) were typically not the greatest contributors to community transcription, suggesting strong top-down ecological control, and their diverse transcriptomes indicated roles as metabolic generalists. The taxa with low in situ growth rates typically had low diversity transcriptomes dominated by specialized metabolisms. By identifying protein-encoding genes with atypically high expression for their level of conservation, unique functional roles of community members emerged related to substrate use (such as complex carbohydrates, fatty acids, methanesulfonate, taurine, tartrate, ectoine), alternative energy-conservation strategies (proteorhodopsin, AAnP, V-type pyrophosphatases, sulfur oxidation, hydrogen oxidation) and mechanisms for negotiating a heterogeneous environment (flagellar motility, gliding motility, adhesion strategies). On average, the heterotrophic bacterioplankton dedicated 7% of their transcriptomes to obtaining energy by non-heterotrophic means. This deep sequencing of a coastal bacterioplankton transcriptome provides the most highly resolved view of bacterioplankton niche dimensions yet available, uncovering a spectrum of unrecognized ecological strategies. PMID:22931830

  16. Comparative proteomic analysis of four Bacillus clausii strains: proteomic expression signature distinguishes protein profile of the strains.

    PubMed

    Lippolis, Rosa; Gnoni, Antonio; Abbrescia, Anna; Panelli, Damiano; Maiorano, Stefania; Paternoster, Maria Stefania; Sardanelli, Anna Maria; Papa, Sergio; Gaballo, Antonio

    2011-11-18

    A comparative proteomic approach, using two dimensional gel electrophoresis and mass spectrometry, has been developed to compare and elucidate the differences among the cellular proteomes of four closely related isogenic O/C, SIN, N/R and T, B. clausii strains during both exponential and stationary phases of growth. Image analysis of the electropherograms reveals a high degree of concordance among the four proteomes, some proteins result, however, differently expressed. The proteins spots exhibiting high different expression level were identified, by mass-spectrometry analysis, as alcohol dehydrogenase (ADHA, EC1.2.1.3; ABC0046 isoform) aldehyde dehydrogenase (DHAS, EC 1.2.1.3; ABC0047 isoform) and flagellin-protein of B. clausii KSM-k16. The different expression levels of the two dehydrogenases were confirmed by quantitative RT-PCR and dehydrogenases enzymatic activity. The different patterns of protein expression can be considered as cell proteome signatures of the different strains.

  17. Expression of the pituitary tumor transforming gene (PTTG1) in pheochromocytoma as a potential marker for distinguishing benign versus malignant tumors.

    PubMed

    Haji Amousha, Mohamad Reza; Sabetkish, Nastaran; Sabet Kish, Nastaran; Heshmat, Ramin; Rajabiani, Afsaneh; Saffar, Hiva; Haghpanah, Vahid; Tavangar, Seyed Mohammad

    2015-01-01

    The Distinction between malignant and benign pheochromocytoma has always been a diagnostic challenge over the last decades. To date, the only reliable criterion is metastasis. The aim of the present study was to investigate the possible expression of pituitary-tumor transforming gene (PTTG1) and retinoblastoma (Rb) in benign and malignant pheochromocytoma. Paraffin blocks of 44 and 11 patients diagnosed with benign and malignant pheochromocytoma were collected. Parameters such as sex, age, tumor size, necrosis, and histological features were compared between the benign and malignant groups as well as immunohistochemical labeling using specific antibodies. PTTG1 showed negative expression in all (44) benign and 9 out of 11 (81.8%) malignant tumors with only 2 out of 11 (18.2%) malignant tumors showed positive reactivity for PTTG1 (P: 0.037) with spindle cell histological pattern in both of them (P: 0.013). Although Rb expression in malignant tumors (81.8%) was slightly more than the benign ones (52.3%), no statistically significant correlation was observed (P: 0.087). These results suggest that PTTG1 immunostaining may play a key role in distinguishing between benign and malignant phaeochromocytoma. However, larger studies are necessary to confirm the outcomes of the present study.

  18. Co-existence of IL7R high and SH2B3 low expression distinguishes a novel high-risk acute lymphoblastic leukemia with Ikaros dysfunction

    PubMed Central

    Ge, Zheng; Gu, Yan; Xiao, Lichan; Han, Qi; Li, Jianyong; Chen, Baoan; Yu, James; Kawasawa, Yuka Imamura; Payne, Kimberly J.; Dovat, Sinisa; Song, Chunhua

    2016-01-01

    Acute lymphoblastic leukemia (ALL) remains the leading cause of cancer-related death in children and young adults. Compared to ALL in children, adult ALL has a much lower cure rate. Therefore, it is important to understand the molecular mechanisms underlying high-risk ALL and to develop therapeutic strategies that specifically target genes or pathways in ALL. Here, we explored the IL7R and SH2B3 expression in adult ALL and found that IL7R is significantly higher and Sh2B3 lower expressed in B-ALL compared to normal bone marrow control, and the IL7RhighSH2B3low is associated with high-risk factors, and with high relapse rate and low disease-free survival rate in the patients. We also found that Ikaros deletion was associated with the IL7RhighSH2B3low expression pattern and Ikaros directly binds the IL7R and SH2B3 promoter, and suppresses IL7R and promotes SH2B3 expression. On the other hand, casein kinase inhibitor, which increases Ikaros function, inhibits IL7R and stimulates SH2B3 expression in an Ikaros dependent manner. Our data indicate that IL7RhighSH2B3low expression distinguishes a novel subset of high-risk B-ALL associated with Ikaros dysfunction, and also suggest the therapeutic potential for treatment that combines casein kinase inhibitor, as an Ikaros activator, with drugs that target the IL7R signaling pathway. PMID:27322554

  19. Genome-wide expression profiling of lymphoblastoid cell lines distinguishes different forms of autism and reveals shared pathways.

    PubMed

    Nishimura, Yuhei; Martin, Christa L; Vazquez-Lopez, Araceli; Spence, Sarah J; Alvarez-Retuerto, Ana Isabel; Sigman, Marian; Steindler, Corinna; Pellegrini, Sandra; Schanen, N Carolyn; Warren, Stephen T; Geschwind, Daniel H

    2007-07-15

    Autism is a heterogeneous condition that is likely to result from the combined effects of multiple genetic factors interacting with environmental factors. Given its complexity, the study of autism associated with Mendelian single gene disorders or known chromosomal etiologies provides an important perspective. We used microarray analysis to compare the mRNA expression profile in lymphoblastoid cells from males with autism due to a fragile X mutation (FMR1-FM), or a 15q11-q13 duplication (dup(15q)), and non-autistic controls. Gene expression profiles clearly distinguished autism from controls and separated individuals with autism based on their genetic etiology. We identified 68 genes that were dysregulated in common between autism with FMR1-FM and dup(15q). We also identified a potential molecular link between FMR1-FM and dup(15q), the cytoplasmic FMR1 interacting protein 1 (CYFIP1), which was up-regulated in dup(15q) patients. We were able to confirm this link in vitro by showing common regulation of two other dysregulated genes, JAKMIP1 and GPR155, downstream of FMR1 or CYFIP1. We also confirmed the reduction of the Jakmip1 protein in Fmr1 knock-out mice, demonstrating in vivo relevance. Finally, we showed independent confirmation of roles for JAKMIP1 and GPR155 in autism spectrum disorders (ASDs) by showing their differential expression in male sib pairs discordant for idiopathic ASD. These results provide evidence that blood derived lymphoblastoid cells gene expression is likely to be useful for identifying etiological subsets of autism and exploring its pathophysiology.

  20. Two different immunostaining patterns of beta-amyloid precursor protein (APP) may distinguish traumatic from nontraumatic axonal injury.

    PubMed

    Hayashi, Takahito; Ago, Kazutoshi; Nakamae, Takuma; Higo, Eri; Ogata, Mamoru

    2015-09-01

    Immunostaining for beta-amyloid precursor protein (APP) is recognized as an effective tool for detecting traumatic axonal injury, but it also detects axonal injury due to ischemic or other metabolic causes. Previously, we reported two different patterns of APP staining: labeled axons oriented along with white matter bundles (pattern 1) and labeled axons scattered irregularly (pattern 2) (Hayashi et al. (Leg Med (Tokyo) 11:S171-173, 2009). In this study, we investigated whether these two patterns are consistent with patterns of trauma and hypoxic brain damage, respectively. Sections of the corpus callosum from 44 cases of blunt head injury and equivalent control tissue were immunostained for APP. APP was detected in injured axons such as axonal bulbs and varicose axons in 24 of the 44 cases of head injuries that also survived for three or more hours after injury. In 21 of the 24 APP-positive cases, pattern 1 alone was observed in 14 cases, pattern 2 alone was not observed in any cases, and both patterns 1 and 2 were detected in 7 cases. APP-labeled injured axons were detected in 3 of the 44 control cases, all of which were pattern 2. These results suggest that pattern 1 indicates traumatic axonal injury, while pattern 2 results from hypoxic insult. These patterns may be useful to differentiate between traumatic and nontraumatic axonal injuries.

  1. Distinguished Books.

    ERIC Educational Resources Information Center

    Marles, Daisy; Ink, Gary

    1999-01-01

    Presents the following lists of distinguished books: "Best Books of 1998"; "Best Young Adult Books"; "Notable Children's Videos"; "Best Children's Books"; "Notable Recordings for Children"; "Notable Software and Web Sites for Children"; "Quick Picks for Reluctant Young Adult…

  2. Simple expressions model antenna radiation patterns

    NASA Astrophysics Data System (ADS)

    Keen, K. M.

    1982-12-01

    A simple method is developed for determining the radiation pattern of antennas, including more directive antennas with irregularly shaped patterns. The method uses the coefficients of a Fourier series determined from field-strength samples taken from the antenna. A computer program is used to provide the solution of several simultaneous equations. This Fourier series technique can be used effectively to represent the main beam region of almost any type of radiation pattern shape. Examples of the use of this method for calculating the radiation pattern of several types of antennas are presented, including a microstrip patch antenna E-plane pattern and the H-plane pattern for an X-band gain horn.

  3. Reduced Il17a expression distinguishes a Ly6c(lo)MHCII(hi) macrophage population promoting wound healing.

    PubMed

    Rodero, Mathieu P; Hodgson, Samantha S; Hollier, Brett; Combadiere, Christophe; Khosrotehrani, Kiarash

    2013-03-01

    Macrophages are the main components of inflammation during skin wound healing. They are critical in wound closure and in excessive inflammation, resulting in defective healing observed in chronic wounds. Given the heterogeneity of macrophage phenotypes and functions, we here hypothesized that different subpopulations of macrophages would have different and sometimes opposing effects on wound healing. Using multimarker flow cytometry and RNA expression array analyses on macrophage subpopulations from wound granulation tissue, we identified a Ly6c(lo)MHCII(hi) "noninflammatory" subset that increased both in absolute number and proportion during normal wound healing and was missing in Ob/Ob and MYD88-/- models of delayed healing. We also identified IL17 as the main cytokine distinguishing this population from proinflammatory macrophages and demonstrated that inhibition of IL17 by blocking Ab or in IL17A-/- mice accelerated normal and delayed healing. These findings dissect the complexity of the role and activity of the macrophages during wound inflammation and may contribute to the development of therapeutic approaches to restore healing in chronic wounds.

  4. Distinguishing similar patterns with different underlying instabilities: effect of advection on systems with Hopf, Turing-Hopf, and wave instabilities.

    PubMed

    Berenstein, Igal

    2012-12-01

    Systems with the same local dynamics but different types of diffusive instabilities may show the same type of patterns. In this paper, we show that under the influence of advective flow the scenario of patterns that is formed at different velocities change; therefore, we propose the use of advective flow as a tool to uncover the underlying instabilities of a reaction-diffusion system.

  5. SATB2 Expression Distinguishes Ovarian Metastases of Colorectal and Appendiceal Origin From Primary Ovarian Tumors of Mucinous or Endometrioid Type.

    PubMed

    Moh, Michelle; Krings, Gregor; Ates, Deniz; Aysal, Anil; Kim, Grace E; Rabban, Joseph T

    2016-03-01

    The primary origin of some ovarian mucinous tumors may be challenging to determine, because some metastases of extraovarian origin may exhibit gross, microscopic, and immunohistochemical features that are shared by some primary ovarian mucinous tumors. Metastases of primary colorectal, appendiceal, gastric, pancreatic, and endocervical adenocarcinomas may simulate primary ovarian mucinous cystadenoma, mucinous borderline tumor, or mucinous adenocarcinoma. Recently, immunohistochemical expression of SATB2, a transcriptional regulator involved in osteoblastic and neuronal differentiation, has been shown to be a highly sensitive marker of normal colorectal epithelium and of colorectal adenocarcinoma. SATB2 expression has not been reported in normal epithelium of the female reproductive tract. Therefore, we hypothesized that SATB2 may be of value in distinguishing ovarian metastases of colorectal adenocarcinoma from primary ovarian mucinous tumors and from primary ovarian endometrioid tumors. Among primary ovarian tumors, SATB2 staining was observed in 0/22 mucinous cystadenomas that lacked a component of mature teratoma, 4/12 mucinous cystadenomas with mature teratoma, 1/60 mucinous borderline tumors, 0/17 mucinous adenocarcinomas, 0/3 endometrioid borderline tumors, and 0/72 endometrioid adenocarcinomas. Among ovarian metastases, SATB2 staining was observed in 24/32 (75%) colorectal adenocarcinomas; 8/10 (80%) low-grade appendiceal mucinous neoplasms; and 4/4 (100%) high-grade appendiceal adenocarcinomas. No SATB2 staining was observed in any ovarian metastasis of pancreatic, gastric, gallbladder, or endocervical origin. Evaluation of primary extraovarian tumors showed the highest incidences of SATB2 staining among primary colorectal adenocarcinomas (71%), primary appendiceal low-grade mucinous neoplasms (100%), and primary appendiceal high-grade adenocarcinomas (100%). Similar to their metastatic counterparts, none of the primary pancreatic or gastric

  6. Differentiating disease subtypes by using pathway patterns constructed from gene expressions and protein networks.

    PubMed

    Hung, Fei-Hung; Chiu, Hung-Wen

    2015-01-01

    Gene expression profiles differ in different diseases. Even if diseases are at the same stage, such diseases exhibit different gene expressions, not to mention the different subtypes at a single lesion site. Distinguishing different disease subtypes at a single lesion site is difficult. In early cases, subtypes were initially distinguished by doctors. Subsequently, further differences were found through pathological experiments. For example, a brain tumor can be classified according to its origin, its cell-type origin, or the tumor site. Because of the advancements in bioinformatics and the techniques for accumulating gene expressions, researchers can use gene expression data to classify disease subtypes. Because the operation of a biopathway is closely related to the disease mechanism, the application of gene expression profiles for clustering disease subtypes is insufficient. In this study, we collected gene expression data of healthy and four myelodysplastic syndrome subtypes and applied a method that integrated protein-protein interaction and gene expression data to identify different patterns of disease subtypes. We hope it is efficient for the classification of disease subtypes in adventure.

  7. Brain morphometric biomarkers distinguishing unipolar and bipolar depression. A voxel-based morphometry-pattern classification approach.

    PubMed

    Redlich, Ronny; Almeida, Jorge J R; Grotegerd, Dominik; Opel, Nils; Kugel, Harald; Heindel, Walter; Arolt, Volker; Phillips, Mary L; Dannlowski, Udo

    2014-11-01

    The structural abnormalities in the brain that accurately differentiate unipolar depression (UD) and bipolar depression (BD) remain unidentified. First, to investigate and compare morphometric changes in UD and BD, and to replicate the findings at 2 independent neuroimaging sites; second, to differentiate UD and BD using multivariate pattern classification techniques. In a 2-center cross-sectional study, structural gray matter data were obtained at 2 independent sites (Pittsburgh, Pennsylvania, and Münster, Germany) using 3-T magnetic resonance imaging. Voxel-based morphometry was used to compare local gray and white matter volumes, and a novel pattern classification approach was used to discriminate between UD and BD, while training the classifier at one imaging site and testing in an independent sample at the other site. The Pittsburgh sample of participants was recruited from the Western Psychiatric Institute and Clinic at the University of Pittsburgh from 2008 to 2012. The Münster sample was recruited from the Department of Psychiatry at the University of Münster from 2010 to 2012. Equally divided between the 2 sites were 58 currently depressed patients with bipolar I disorder, 58 age- and sex-matched unipolar depressed patients, and 58 matched healthy controls. Magnetic resonance imaging was used to detect structural differences between groups. Morphometric analyses were applied using voxel-based morphometry. Pattern classification techniques were used for a multivariate approach. At both sites, individuals with BD showed reduced gray matter volumes in the hippocampal formation and the amygdala relative to individuals with UD (Montreal Neurological Institute coordinates x = -22, y = -1, z = 20; k = 1938 voxels; t = 4.75), whereas individuals with UD showed reduced gray matter volumes in the anterior cingulate gyrus compared with individuals with BD (Montreal Neurological Institute coordinates x = -8, y = 32, z = 3; k

  8. Pharmacology of GABAC receptors: responses to agonists and antagonists distinguish A- and B-subtypes of homomeric rho receptors expressed in Xenopus oocytes.

    PubMed

    Pan, Yi; Khalili, Parham; Ripps, Harris; Qian, Haohua

    2005-03-07

    GABA(C) receptors, expressed predominantly in vertebrate retina, are thought to be formed mainly by GABA rho subunits. Five GABA rho subunits have been cloned from white perch retina, four of which form functional homooligomeric receptors when expressed in Xenopus oocytes. These rho subtypes, classified as rho1A, rho1B, rho2A and rho2B receptors based on amino acid sequence alignment, exhibit distinct temporal and pharmacological properties. To examine further the pharmacological properties associated with the various rho receptor subtypes, we investigated the effects of a selective GABA(C) receptor antagonist, TPMPA, on the GABA-mediated activity of receptors formed in Xenopus oocytes by the four GABA rho subunits. In addition, we recorded the activation profiles of beta-alanine, taurine, and glycine, three amino acids that modulate neuronal activity in various parts of the CNS and are purported to be rho receptor agonists. TPMPA effectively inhibited GABA-elicited responses on A-type receptors, whereas B-type receptors exhibited a relatively low sensitivity to the drug. A-type and B-type receptors also displayed distinctly different reactions to agonists. Both taurine and glycine-activated the B-type receptors, whereas these agents had no detectable effect on A-type receptors. Similarly, beta-alanine evoked large responses from B-type receptors, but was far less effective on A-type receptors. These results indicate that, in addition to the characteristic response properties identified previously, there is a pattern of pharmacological reactions that further distinguishes the A- and B-subtypes of GABA rho receptor.

  9. A family of null models to distinguish between environmental filtering and biotic interactions in functional diversity patterns

    PubMed Central

    Chalmandrier, L.; Müunkemüller, T.; Gallien, L.; de Bello, F.; Mazel, F.; Lavergne, S.; Thuiller, W.

    2014-01-01

    Questions Traditional null models used to reveal assembly processes from functional diversity patterns are not tailored for comparing different spatial and evolutionary scales. In this study, we present and explore a family of null models that can help disentangling assembly processes at their appropriate scales and thereby elucidate the ecological drivers of community assembly. Location French Alps. Methods Our approach gradually constrains null models by: (1) filtering out species not able to survive in the regional conditions in order to reduce the spatial scale, and (2) shuffling species only within lineages of different ages to reduce the evolutionary scale of the analysis. We first tested and validated this approach using simulated communities. We then applied it to study the functional diversity patterns of the leaf–height–seed strategy of plant communities in the French Alps. Results Using simulations, we found that reducing the spatial scale correctly detected a signature of competition (functional divergence) even when environmental filtering produced an overlaying signal of functional convergence. However, constraining the evolutionary scale did not change the identified functional diversity patterns. In the case study of alpine plant communities, investigating scale effects revealed that environmental filtering had a strong influence at larger spatial and evolutionary scales and that neutral processes were more important at smaller scales. In contrast to the simulation study results, decreasing the evolutionary scale tended to increase patterns of functional divergence. Conclusion We argue that the traditional null model approach can only identify a single main process at a time and suggest to rather use a family of null models to disentangle intertwined assembly processes acting across spatial and evolutionary scales. PMID:24791143

  10. Patterns of activity expressed by juvenile horseshoe crabs.

    PubMed

    Dubofsky, E A; Simpson, S D; Chabot, Christopher C; Watson, Winsor H

    2013-09-01

    Adult American horseshoe crabs, Limulus polyphemus, possess endogenous circadian and circatidal clocks controlling visual sensitivity and locomotion, respectively. The goal of this study was to determine the types of activity rhythms expressed by juvenile horseshoe crabs (n = 24) when exposed to a 14:10 light/dark cycle (LD) for 10 days, followed by 10 days of constant darkness (DD). Horseshoe crab activity was recorded with a digital time-lapse video system that used an infrared-sensitive camera so animals could be monitored at night. In LD, 15 animals expressed daily patterns of activity, 6 displayed a circatidal pattern, and the remaining 3 were arrhythmic. Of the 15 animals with daily patterns of locomotion, 7 had a significant preference (P < 0.05) for diurnal activity and 3 for nocturnal activity; the remainder did not express a significant preference for day or night activity. In DD, 13 horseshoe crabs expressed circatidal rhythms and 8 maintained a pattern of about 24 h. Although these results suggest the presence of a circadian clock influencing circatidal patterns of locomotion, these apparent circadian rhythms may actually represent the expression of just one of the two bouts of activity driven by the putative circalunidian clocks that control their tidal rhythms. Overall, these results indicate that, like adults, juvenile horseshoe crabs express both daily and tidal patterns of activity and that at least one, and maybe both, of these patterns is driven by endogenous clocks.

  11. Using multispectral videography to distinguish the pattern of zonation and plant species composition in brackish water marshes of the Rio Grande Delta

    SciTech Connect

    Judd, F.W.; Lonard, R.I.; Everitt, J.H.

    1997-08-01

    Cyclical flooding of the Rio Grande and movement of floodwater into distributary channels formerly constituted significant freshwater input into the marshes of the Rio Grande Delta, but dams and flood control projects have eliminated this source of freshwater. The marshes are now dependent on rainfall alone for freshwater input and may be experiencing significant change in species of vegetation, abundance and patterns of distribution. Unfortunately, little is known of the ecology of these marshes. As a first step in providing needed information, multispectral videography was used to distinguish species composition and patterns of zonation in a brackish water marsh at Laguna Atascosa National Wildlife Refuge, Cameron County, Texas. The line intercept method of vegetation analysis provided ground truth and quantified species distribution and abundance. The vegetation of a typical brackish water marsh is organized into three zones along an elevation gradient. At the lowest elevations there is a distinct zone dominated by maritime saltwort, Batis maritime. At the lowest elevations in this zone where rainwater remains the longest, stands of California bulrush, Scirpus californicus, occur. An intermediate zone supports shoregrass, Monanthochloe littoralis, as the dominant species. A third (highest) zone is dominated by Gulf cordgrass, Spartina spartinae. The upper margin of this zone grades gradually into a shrub-grassland community that occurs on lomas (clay dunes). Each of the zones is distinguished by a distinctive signature in the multispectral videography. The Batis maritime community has a bright pink to red image response. Monanthochloe littoralis has a dark brown color and Spartina spartinae has a light gray to pinkish-tan color. Brackish water marshes may be distinguished from saltwater marshes by the relative positions of the Monanthochloe littoralis and Spartina spartinae communities, but additional data are needed before this possibility is confirmed.

  12. Broadly expressed repressors integrate patterning across orthogonal axes in embryos.

    PubMed

    Koromila, Theodora; Stathopoulos, Angelike

    2017-07-18

    The role of spatially localized repressors in supporting embryonic patterning is well appreciated, but, alternatively, the role ubiquitously expressed repressors play in this process is not well understood. We investigated the function of two broadly expressed repressors, Runt (Run) and Suppressor of Hairless [Su(H)], in patterning the Drosophila embryo. Previous studies have shown that Run and Su(H) regulate gene expression along anterior-posterior (AP) or dorsal-ventral (DV) axes, respectively, by spatially limiting activator action, but here we characterize a different role. Our data show that broadly expressed repressors silence particular enhancers within cis-regulatory systems, blocking their expression throughout the embryo fully but transiently, and, in this manner, regulate spatiotemporal outputs along both axes. Our results suggest that Run and Su(H) regulate the temporal action of enhancers and are not dedicated regulators of one axis but, instead, act coordinately to pattern both axes, AP and DV.

  13. Differential infection patterns of CD4+ T cells and lymphoid tissue viral burden distinguish progressive and nonprogressive lentiviral infections

    PubMed Central

    Vinton, Carol; Tabb, Brian; Hao, Xing Pei; Connick, Elizabeth; Paiardini, Mirko; Lifson, Jeffrey D.; Silvestri, Guido

    2012-01-01

    Nonhuman primate natural hosts for simian immunodeficiency viruses (SIV) develop a nonresolving chronic infection but do not develop AIDS. Mechanisms to explain the nonprogressive nature of SIV infection in natural hosts that underlie maintained high levels of plasma viremia without apparent loss of target cells remain unclear. Here we used comprehensive approaches (ie, FACS sorting, quantitative RT-PCR, immunohistochemistry, and in situ hybridization) to study viral infection within subsets of peripheral blood and lymphoid tissue (LT) CD4+ T cells in cohorts of chronically SIV-infected rhesus macaques (RMs), HIV-infected humans, and SIVsmm-infected sooty mangabeys (SMs). We find: (1) infection frequencies among CD4+ T cells in chronically SIV-infected RMs are significantly higher than those in SIVsmm-infected SMs; (2) infected cells are found in distinct anatomic LT niches and different CD4+ T-cell subsets in SIV-infected RMs and SMs, with infection patterns of RMs reflecting HIV infection in humans; (3) TFH cells are infected at higher frequencies in RMs and humans than in SMs; and (4) LT viral burden, including follicular dendritic cell deposition of virus, is increased in RMs and humans compared with SMs. These data provide insights into how natural hosts are able to maintain high levels of plasma viremia while avoiding development of immunodeficiency. PMID:22990012

  14. Robust stratification of breast cancer subtypes using differential patterns of transcript isoform expression.

    PubMed

    Stricker, Thomas P; Brown, Christopher D; Bandlamudi, Chaitanya; McNerney, Megan; Kittler, Ralf; Montoya, Vanessa; Peterson, April; Grossman, Robert; White, Kevin P

    2017-03-01

    Breast cancer, the second leading cause of cancer death of women worldwide, is a heterogenous disease with multiple different subtypes. These subtypes carry important implications for prognosis and therapy. Interestingly, it is known that these different subtypes not only have different biological behaviors, but also have distinct gene expression profiles. However, it has not been rigorously explored whether particular transcriptional isoforms are also differentially expressed among breast cancer subtypes, or whether transcript isoforms from the same sets of genes can be used to differentiate subtypes. To address these questions, we analyzed the patterns of transcript isoform expression using a small set of RNA-sequencing data for eleven Estrogen Receptor positive (ER+) subtype and fourteen triple negative (TN) subtype tumors. We identified specific sets of isoforms that distinguish these tumor subtypes with higher fidelity than standard mRNA expression profiles. We found that alternate promoter usage, alternative splicing, and alternate 3'UTR usage are differentially regulated in breast cancer subtypes. Profiling of isoform expression in a second, independent cohort of 68 tumors confirmed that expression of splice isoforms differentiates breast cancer subtypes. Furthermore, analysis of RNAseq data from 594 cases from the TCGA cohort confirmed the ability of isoform usage to distinguish breast cancer subtypes. Also using our expression data, we identified several RNA processing factors that were differentially expressed between tumor subtypes and/or regulated by estrogen receptor, including YBX1, YBX2, MAGOH, MAGOHB, and PCBP2. RNAi knock-down of these RNA processing factors in MCF7 cells altered isoform expression. These results indicate that global dysregulation of splicing in breast cancer occurs in a subtype-specific and reproducible manner and is driven by specific differentially expressed RNA processing factors.

  15. Robust stratification of breast cancer subtypes using differential patterns of transcript isoform expression

    PubMed Central

    Stricker, Thomas P.; Bandlamudi, Chaitanya; Kittler, Ralf; Montoya, Vanessa; Peterson, April; Grossman, Robert

    2017-01-01

    Breast cancer, the second leading cause of cancer death of women worldwide, is a heterogenous disease with multiple different subtypes. These subtypes carry important implications for prognosis and therapy. Interestingly, it is known that these different subtypes not only have different biological behaviors, but also have distinct gene expression profiles. However, it has not been rigorously explored whether particular transcriptional isoforms are also differentially expressed among breast cancer subtypes, or whether transcript isoforms from the same sets of genes can be used to differentiate subtypes. To address these questions, we analyzed the patterns of transcript isoform expression using a small set of RNA-sequencing data for eleven Estrogen Receptor positive (ER+) subtype and fourteen triple negative (TN) subtype tumors. We identified specific sets of isoforms that distinguish these tumor subtypes with higher fidelity than standard mRNA expression profiles. We found that alternate promoter usage, alternative splicing, and alternate 3’UTR usage are differentially regulated in breast cancer subtypes. Profiling of isoform expression in a second, independent cohort of 68 tumors confirmed that expression of splice isoforms differentiates breast cancer subtypes. Furthermore, analysis of RNAseq data from 594 cases from the TCGA cohort confirmed the ability of isoform usage to distinguish breast cancer subtypes. Also using our expression data, we identified several RNA processing factors that were differentially expressed between tumor subtypes and/or regulated by estrogen receptor, including YBX1, YBX2, MAGOH, MAGOHB, and PCBP2. RNAi knock-down of these RNA processing factors in MCF7 cells altered isoform expression. These results indicate that global dysregulation of splicing in breast cancer occurs in a subtype-specific and reproducible manner and is driven by specific differentially expressed RNA processing factors. PMID:28263985

  16. Circadian Control of Global Gene Expression Patterns

    PubMed Central

    Doherty, Colleen J.; Kay, Steve A.

    2014-01-01

    An internal time-keeping mechanism has been observed in almost every organism studied from archaea to humans. This circadian clock provides a competitive advantage in fitness and survival (18, 30, 95, 129, 137). Researchers have uncovered the molecular composition of this internal clock by combining enzymology, molecular biology, genetics, and modeling approaches. However, understanding the mechanistic link between the clock and output responses has been elusive. In three model organisms, Arabidopsis thaliana, Drosophila melanogaster, and Mus musculus, whole-genome expression arrays have enabled researchers to investigate how maintaining a time-keeping mechanism connects to an adaptive advantage. Here, we review the impacts transcriptomics have had on our understanding of the clock and how this molecular clock connects with system-level circadian responses. We explore the discoveries made possible by high-throughput RNA assays, the network approaches used to investigate these large transcript datasets, and potential future directions. PMID:20809800

  17. Divergent and nonuniform gene expression patterns in mouse brain

    PubMed Central

    Morris, John A.; Royall, Joshua J.; Bertagnolli, Darren; Boe, Andrew F.; Burnell, Josh J.; Byrnes, Emi J.; Copeland, Cathy; Desta, Tsega; Fischer, Shanna R.; Goldy, Jeff; Glattfelder, Katie J.; Kidney, Jolene M.; Lemon, Tracy; Orta, Geralyn J.; Parry, Sheana E.; Pathak, Sayan D.; Pearson, Owen C.; Reding, Melissa; Shapouri, Sheila; Smith, Kimberly A.; Soden, Chad; Solan, Beth M.; Weller, John; Takahashi, Joseph S.; Overly, Caroline C.; Lein, Ed S.; Hawrylycz, Michael J.; Hohmann, John G.; Jones, Allan R.

    2010-01-01

    Considerable progress has been made in understanding variations in gene sequence and expression level associated with phenotype, yet how genetic diversity translates into complex phenotypic differences remains poorly understood. Here, we examine the relationship between genetic background and spatial patterns of gene expression across seven strains of mice, providing the most extensive cellular-resolution comparative analysis of gene expression in the mammalian brain to date. Using comprehensive brainwide anatomic coverage (more than 200 brain regions), we applied in situ hybridization to analyze the spatial expression patterns of 49 genes encoding well-known pharmaceutical drug targets. Remarkably, over 50% of the genes examined showed interstrain expression variation. In addition, the variability was nonuniformly distributed across strain and neuroanatomic region, suggesting certain organizing principles. First, the degree of expression variance among strains mirrors genealogic relationships. Second, expression pattern differences were concentrated in higher-order brain regions such as the cortex and hippocampus. Divergence in gene expression patterns across the brain could contribute significantly to variations in behavior and responses to neuroactive drugs in laboratory mouse strains and may help to explain individual differences in human responsiveness to neuroactive drugs. PMID:20956311

  18. Gene Expression patterns in cryogenically stored Arabidopsis thaliana shoot tips

    USDA-ARS?s Scientific Manuscript database

    The genes expressed in response to cryostress in plant shoot tips are not known. In this project we compared the gene expression patterns in untreated, cryoprotectant-treated, and recovering shoot tips using differential display methods. This project identified two genes that appeared to be differ...

  19. Post hoc pattern matching: assigning significance to statistically defined expression patterns in single channel microarray data

    PubMed Central

    Hulshizer, Randall; Blalock, Eric M

    2007-01-01

    Background Researchers using RNA expression microarrays in experimental designs with more than two treatment groups often identify statistically significant genes with ANOVA approaches. However, the ANOVA test does not discriminate which of the multiple treatment groups differ from one another. Thus, post hoc tests, such as linear contrasts, template correlations, and pairwise comparisons are used. Linear contrasts and template correlations work extremely well, especially when the researcher has a priori information pointing to a particular pattern/template among the different treatment groups. Further, all pairwise comparisons can be used to identify particular, treatment group-dependent patterns of gene expression. However, these approaches are biased by the researcher's assumptions, and some treatment-based patterns may fail to be detected using these approaches. Finally, different patterns may have different probabilities of occurring by chance, importantly influencing researchers' conclusions about a pattern and its constituent genes. Results We developed a four step, post hoc pattern matching (PPM) algorithm to automate single channel gene expression pattern identification/significance. First, 1-Way Analysis of Variance (ANOVA), coupled with post hoc 'all pairwise' comparisons are calculated for all genes. Second, for each ANOVA-significant gene, all pairwise contrast results are encoded to create unique pattern ID numbers. The # genes found in each pattern in the data is identified as that pattern's 'actual' frequency. Third, using Monte Carlo simulations, those patterns' frequencies are estimated in random data ('random' gene pattern frequency). Fourth, a Z-score for overrepresentation of the pattern is calculated ('actual' against 'random' gene pattern frequencies). We wrote a Visual Basic program (StatiGen) that automates PPM procedure, constructs an Excel workbook with standardized graphs of overrepresented patterns, and lists of the genes comprising

  20. Aberrant immunoarchitecture distinguishes hyperplastic germinal centres in pattern 1 angioimmunoblastic T-cell lymphoma from reactive follicles.

    PubMed

    Tan, Leonard Hwan-Cheong; Tan, Soo-Yong

    2014-09-01

    We compare 30 biopsies each of Pattern 1 angioimmunoblastic T-cell lymphoma (AITL1) and reactive lymphoid hyperplasia (RLH) by immunohistology, in-situ hybridization for Epstein-Barr virus-encoded RNA and T-cell receptor-γ (TRG)-clonality. AITL1 cases, more often than RLH controls, were older [median ages 61 (range 23-79) vs 46 (range 11-59) years, p < 10(-4)], non-Chinese [16/30 (53%) vs 8/28 (29%), p = 0.035], presented nodally [29/30 (97%) vs 23/30 (77%), p = 0.024], showed: pan-T cell antigen attenuation [25/29 (86%) vs 5/21 (24%), p = 1.0 × 10(-5)], CD4 predominance [25/28 (89%) vs 12/23 (52%), p = 3.4 × 10(-3)], interfollicular lymphoid CD10-positivity [16/30 (53%) vs 1/29 (3%), p = 1.5 × 10(-5)], TRG clonality [16/28 (57%) vs 1/20 (5%), p = 1.4 × 10(-4)], higher maximum number of Epstein-Barr virus-encoded RNA + nuclei per 0.5-mm high-power field [median 6 (range 0-70) vs 1 (range 0-40), p = 0.012] and interfollicular Ki-67 proliferation fraction [median 40% (range 10-80%) vs 20% (range 5-40), p < 10(-4)], whereas their germinal centres (GCs) more often showed attenuation of CD10 [30/30 (100%) vs 11/29 (38%), p = 5.3 × 10(-8)] and CD57 [18/25 (72%) vs 4/22 (18%), p = 2.4 × 10(-4)] (respectively). GC-predominant PD-1 and ICOS immunoreactivity were more often seen in RLH [20/22 and 9/19 controls (91% and 47%)] than AITL1 [9/25 and 3/19 cases (36% and 16%), p = 1.0 × 10(-4) and 0.033, respectively]. Significant independent predictors against AITL1 were: solid GC CD10 immunoreactivity {p = 0.023, odds ratio (OR) for AITL1 0.01 [95% confidence interval (CI): 0.0002-0.529]}; lower interfollicular proliferation fraction [p = 0.047, OR for AITL1 1.1 (95% CI: 1.001-1.209) per % rise in Ki-67]; younger presenting age [p = 0.028, OR for AITL1 1.136 (95% CI: 1.014-1.272) per year older]. Hence, GCs and perifollicular zones in AITL1 are distinct from those in RLH.

  1. Distinguishing polyfunctional from monofunctional acids and bases by acid-base titrimetry, multiparametric curve-fitting, and deviation-pattern recognition.

    PubMed

    Meites, L; Barry, D M

    1973-11-01

    A new technique for distinguishing diacidic from monoacidic weak bases (or dibasic from monobasic weak acids) is based on fitting the data obtained in a potentiometric acid-base titration to theoretical equations for the titration of a monoacidic base (or monobasic acid). If the substance titrated is not monofunctional the best fit to these equations will involve systematic deviations that, when plotted against the volume of reagent, yield a "deviation pattern" with a shape characteristic of polyfunctional behaviour. Ancillary criteria based on the values of the parameters obtained from the fit are also described. There is a range of uncertainty associated with each of these criteria in which the ratios of successive dissociation constants are so close to the statistical values that it is impossible in the face of the errors of measurement to decide whether the substance is monofunctional or polyfunctional. If the data from one titration prove to lie within that range, the decision may be based on the results of a second titration performed at a different ionic strength. Further fitting to the equations describing more complex behaviour provides a basis for distinguishing non-statistical difunctional substances from trifunctional ones, trifunctional ones from tetrafunctional ones, and so on.

  2. Distalless expression in crustaceans and the patterning of branched limbs.

    PubMed

    Williams, T A

    1998-01-01

    In Drosophila, Distalless (Dll) is critical in establishing the proximal/distal axis of the leg. Lack of proper Dll expression causes distal limb structures to be truncated or lost. Dll expression was examined through the course of development in the limbs of two crustaceans, Triops and Nebalia. Because the limbs of these two species are branched, they provide a comparison to the uniramous (unbranched) leg of Drosophila. In Triops and Nebalia, development of limb branches is not tightly coupled with Dll expression: in some cases, branches can arise prior to Dll expression and in others, certain branches never express Dll. These data suggest that, while Dll may indeed initiate overall limb outgrowth, limb branches are unlikely to be patterned by a simple iteration of the mechanism patterning the unbranched leg of Drosophila.

  3. Are herb-pairs of traditional Chinese medicine distinguishable from others? Pattern analysis and artificial intelligence classification study of traditionally defined herbal properties.

    PubMed

    Ung, Choong Yong; Li, Hu; Cao, Zhi Wei; Li, Yi Xue; Chen, Yu Zong

    2007-05-04

    Multi-herb prescriptions of traditional Chinese medicine (TCM) often include special herb-pairs for mutual enhancement, assistance, and restraint. These TCM herb-pairs have been assembled and interpreted based on traditionally defined herbal properties (TCM-HPs) without knowledge of mechanism of their assumed synergy. While these mechanisms are yet to be determined, properties of TCM herb-pairs can be investigated to determine if they exhibit features consistent with their claimed unique synergistic combinations. We analyzed distribution patterns of TCM-HPs of TCM herb-pairs to detect signs indicative of possible synergy and used artificial intelligence (AI) methods to examine whether combination of their TCM-HPs are distinguishable from those of non-TCM herb-pairs assembled by random combinations and by modification of known TCM herb-pairs. Patterns of the majority of 394 known TCM herb-pairs were found to exhibit signs of herb-pair correlation. Three AI systems, trained and tested by using 394 TCM herb-pairs and 2470 non-TCM herb-pairs, correctly classified 72.1-87.9% of TCM herb-pairs and 91.6-97.6% of the non-TCM herb-pairs. The best AI system predicted 96.3% of the 27 known non-TCM herb-pairs and 99.7% of the other 1,065,100 possible herb-pairs as non-TCM herb-pairs. Our studies suggest that TCM-HPs of known TCM herb-pairs contain features distinguishable from those of non-TCM herb-pairs consistent with their claimed synergistic or modulating combinations.

  4. Arabidopsis gene expression patterns are altered during spaceflight

    NASA Astrophysics Data System (ADS)

    Paul, Anna-Lisa; Popp, Michael P.; Gurley, William B.; Guy, Charles; Norwood, Kelly L.; Ferl, Robert J.

    The exposure of Arabidopsis thaliana (Arabidopsis) plants to spaceflight environments results in differential gene expression. A 5-day mission on orbiter Columbia in 1999 (STS-93) carried transgenic Arabidopsis plants engineered with a transgene composed of the alcohol dehydrogenase (Adh) gene promoter linked to the β-Glucuronidase (GUS) reporter gene. The plants were used to evaluate the effects of spaceflight on gene expression patterns initially by using the Adh/GUS transgene to address specifically the possibility that spaceflight induces a hypoxic stress response (Paul, A.L., Daugherty, C.J., Bihn, E.A., Chapman, D.K., Norwood, K.L., Ferl, R.J., 2001. Transgene expression patterns indicate that spaceflight affects stress signal perception and transduction in arabidopsis, Plant Physiol. 126, 613-621). As a follow-on to the reporter gene analysis, we report here the evaluation of genome-wide patterns of native gene expression within Arabidopsis shoots utilizing the Agilent DNA array of 21,000 Arabidopsis genes. As a control for the veracity of the array analyses, a selection of genes was further characterized with quantitative Real-Time RT PCR (ABI - Taqman®). Comparison of the patterns of expression for arrays probed with RNA isolated from plants exposed to spaceflight compared to RNA isolated from ground control plants revealed 182 genes that were differentially expressed in response to the spaceflight mission by more than 4-fold, and of those only 50 genes were expressed at levels chosen to support a conservative change call. None of the genes that are hallmarks of hypoxic stress were induced to this level. However, genes related to heat shock were dramatically induced - but in a pattern and under growth conditions that are not easily explained by elevated temperatures. These gene expression data are discussed in light of current models for plant responses to the spaceflight environment and with regard to potential future spaceflight experiment

  5. G-protein coupled receptor expression patterns delineate medulloblastoma subgroups

    PubMed Central

    2013-01-01

    Background Medulloblastoma is the most common malignant brain tumor in children. Genetic profiling has identified four principle tumor subgroups; each subgroup is characterized by different initiating mutations, genetic and clinical profiles, and prognoses. The two most well-defined subgroups are caused by overactive signaling in the WNT and SHH mitogenic pathways; less is understood about Groups 3 and 4 medulloblastoma. Identification of tumor subgroup using molecular classification is set to become an important component of medulloblastoma diagnosis and staging, and will likely guide therapeutic options. However, thus far, few druggable targets have emerged. G-protein coupled receptors (GPCRs) possess characteristics that make them ideal targets for molecular imaging and therapeutics; drugs targeting GPCRs account for 30-40% of all current pharmaceuticals. While expression patterns of many proteins in human medulloblastoma subgroups have been discerned, the expression pattern of GPCRs in medulloblastoma has not been investigated. We hypothesized that analysis of GPCR expression would identify clear subsets of medulloblastoma and suggest distinct GPCRs that might serve as molecular targets for both imaging and therapy. Results Our study found that medulloblastoma tumors fall into distinct clusters based solely on GPCR expression patterns. Normal cerebellum clustered separately from the tumor samples. Further, two of the tumor clusters correspond with high fidelity to the WNT and SHH subgroups of medulloblastoma. Distinct over-expressed GPCRs emerge; for example, LGR5 and GPR64 are significantly and uniquely over-expressed in the WNT subgroup of tumors, while PTGER4 is over-expressed in the SHH subgroup. Uniquely under-expressed GPCRs were also observed. Our key findings were independently validated using a large international dataset. Conclusions Our results identify GPCRs with potential to act as imaging and therapeutic targets. Elucidating tumorigenic pathways

  6. Analysis of HOX gene expression patterns in human breast cancer.

    PubMed

    Hur, Ho; Lee, Ji-Yeon; Yun, Hyo Jung; Park, Byeong Woo; Kim, Myoung Hee

    2014-01-01

    HOX genes are highly conserved transcription factors that determine the identity of cells and tissues along the anterior-posterior body axis in developing embryos. Aberrations in HOX gene expression have been shown in various tumors. However, the correlation of HOX gene expression patterns with tumorigenesis and cancer progression has not been fully characterized. Here, to analyze putative candidate HOX genes involved in breast cancer tumorigenesis and progression, the expression patterns of 39 HOX genes were analyzed using breast cancer cell lines and patient-derived breast tissues. In vitro analysis revealed that HOXA and HOXB gene expression occurred in a subtype-specific manner in breast cancer cell lines, whereas most HOXC genes were strongly expressed in most cell lines. Among the 39 HOX genes analyzed, 25 were chosen for further analysis in malignant and non-malignant tissues. Fourteen genes, encoding HOXA6, A13, B2, B4, B5, B6, B7, B8, B9, C5, C9, C13, D1, and D8, out of 25 showed statistically significant differential expression patterns between non-malignant and malignant breast tissues and are putative candidates associated with the development and malignant progression of breast cancer. Our data provide a valuable resource for furthering our understanding of HOX gene expression in breast cancer and the possible involvement of HOX genes in tumor progression.

  7. Fgf19 expression patterns in the developing chick inner ear.

    PubMed

    Sánchez-Calderón, Hortensia; Francisco-Morcillo, Javier; Martín-Partido, Gervasio; Hidalgo-Sánchez, Matías

    2007-01-01

    The inner ear is a complex sensorial structure with hearing and balance functions. A key aim of developmental biology is to understand the molecular and cellular mechanisms involved in the induction, patterning and innervation of the vertebrate inner ear. These developmental events could be mediated by the expression of regulating genes, such as the members of the family of Fibroblast Growth Factors (Fgfs). This work reports the detailed spatial and temporal patterns of Fgf19 expression in the developing inner ear from otic cup (stage 14) to 8 embryonic days (stage 34). In the earliest stages, Fgf19 and Fgf8 expressions determine two subdomains within the Fgf10-positive proneural-sensory territory. We show that, from the earliest stages, the Fgf19 expression was detected in the acoustic-vestibular ganglion and the macula utriculi. The Fgf19 gene was also strongly, but transiently, expressed in the macula lagena, whereas the macula neglecta never expressed this gene in the period analysed. The Fgf19 expression was also clearly observed in some borders of various sensory elements. These results could be useful from further investigations into the role of FGF19 in otic patterning.

  8. The mirror RNA expression pattern in human tissues

    PubMed Central

    Bythwood, Tameka N.; Xu, Wei; Li, Wenzhi; Rao, Weinian; Li, Qiling; Xue, Xue; Richards, Jendai; Ma, Li; Song, Qing

    2017-01-01

    It has been realized in recent years that non-coding RNAs are playing important roles in genome functions and human diseases. Here we developed a new technology and observed a new pattern of gene expression. We observed that over 72% of RNAs in human genome are expressed in forward-reverse pairs, just like mirror images of each other between forward expression and reverse expression; the overview showed that it cannot be simply described as transcript overlapping, so we designated it as mirror expression. Furthermore, we found that the mirror expression is gene-specific and tissue-specific, and less common in the proximal promoter regions. The size of the shadows varies between different genes, different tissues and different classes. The shadow expression is most significant in the Alu element, it was also observed among L1, Simple Repeats and LTR elements, but rare in other repeats such as low-complexity, LINE/L2, DNA and MIRs. Although there is no evidence yet about the relationship of this mirror pattern and double-strand RNA (dsRNA), this new striking pattern provides a new clue and a new direction to unveil the role of RNAs in the genome functions and diseases.

  9. Expression pattern analysis of microRNAs in Caenorhabditis elegans.

    PubMed

    Isik, Meltem; Berezikov, Eugene

    2013-01-01

    MicroRNAs (miRNAs) are ∼22 nucleotide single-stranded RNA molecules that originate from hairpin precursors and regulate gene expression at the posttranscriptional level by basepairing with target messenger RNA and blocking its translation or inducing its degradation. miRNAs play important roles in a variety of biological processes, including development, proliferation, differentiation, cell fate determination, apoptosis, signal transduction, host-viral interactions, and tumorigenesis. Methodological advances in miRNA studies allowed identification of biological roles for many miRNAs, and establishing the spatiotemporal expression patterns of miRNAs is one of the approaches to elucidate their biological functions. Expression pattern analysis of miRNAs helps to identify potential genetic interactors that exhibit similar expression patterns and this, combined with further supporting experiments, helps to identify the genetic pathways in which the specific miRNAs are involved. In this chapter, we describe a detailed protocol for the analysis of miRNA expression patterns in Caenorhabditis elegans.

  10. Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism

    PubMed Central

    Jiang, Xi; Hu, Haiyang; Guijarro, Patricia; Mitchell, Amanda; Ely, John J.; Sherwood, Chet C.; Hof, Patrick R.; Qiu, Zilong; Pääbo, Svante; Akbarian, Schahram; Khaitovich, Philipp

    2016-01-01

    Cognitive defects in autism spectrum disorder (ASD) include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR) transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans. PMID:27685936

  11. Distinct parasegmental and imaginal enhancers and the establishment of the expression pattern of the Ubx gene

    SciTech Connect

    Pirrotta, V.; Chan, Chi Shing; McCabe, D.; Qian, Su

    1995-12-01

    The expression domain of the Ubx gene in Drosophila embryos is bounded by the product of the hb gene, acting as a repressor. We show that all Ubx fragments that bind Hb protein in vitro contain parasegmental enhancers active in the embryo in specific parasegmental patterns. We have found three new embryonic enhancer elements in the upstream region, in addition to the two previously identified. Each produces a pattern initially bounded at PS6 by Hb but sooner or later breaks down this boundary and begins to express in the anterior region. These enhancers do not respond to the long-term maintenance mediated by the Polycomb group of genes. They also cease functioning after germ band extension. Expression in imaginal tissues is due to a set of entirely separate and independent imaginal disc enhancers. These do not contain Hb binding sites and by themselves have no anterior/posterior positional information, although some distinguish between ventral and dorsal discs. A third kind of element, the Polycomb Response Element (PRE), has no enhancer activity but causes long-term maintenance of the expression domain of other enhancers present in the vicinity. The interaction of these elements results in the correct expression of Ubx in imaginal tissues. 40 refs., 7 figs.

  12. A regulatory network controls nephrocan expression and midgut patterning

    PubMed Central

    Hou, Juan; Wei, Wei; Saund, Ranajeet S.; Xiang, Ping; Cunningham, Thomas J.; Yi, Yuyin; Alder, Olivia; Lu, Daphne Y. D.; Savory, Joanne G. A.; Krentz, Nicole A. J.; Montpetit, Rachel; Cullum, Rebecca; Hofs, Nicole; Lohnes, David; Humphries, R. Keith; Yamanaka, Yojiro; Duester, Gregg; Saijoh, Yukio; Hoodless, Pamela A.

    2014-01-01

    Although many regulatory networks involved in defining definitive endoderm have been identified, the mechanisms through which these networks interact to pattern the endoderm are less well understood. To explore the mechanisms involved in midgut patterning, we dissected the transcriptional regulatory elements of nephrocan (Nepn), the earliest known midgut specific gene in mice. We observed that Nepn expression is dramatically reduced in Sox17−/− and Raldh2−/− embryos compared with wild-type embryos. We further show that Nepn is directly regulated by Sox17 and the retinoic acid (RA) receptor via two enhancer elements located upstream of the gene. Moreover, Nepn expression is modulated by Activin signaling, with high levels inhibiting and low levels enhancing RA-dependent expression. In Foxh1−/− embryos in which Nodal signaling is reduced, the Nepn expression domain is expanded into the anterior gut region, confirming that Nodal signaling can modulate its expression in vivo. Together, Sox17 is required for Nepn expression in the definitive endoderm, while RA signaling restricts expression to the midgut region. A balance of Nodal/Activin signaling regulates the anterior boundary of the midgut expression domain. PMID:25209250

  13. MEPD: medaka expression pattern database, genes and more

    PubMed Central

    Alonso-Barba, Juan I.; Rahman, Raza-Ur; Wittbrodt, Joachim; Mateo, Juan L.

    2016-01-01

    The Medaka Expression Pattern Database (MEPD; http://mepd.cos.uni-heidelberg.de/) is designed as a repository of medaka expression data for the scientific community. In this update we present two main improvements. First, we have changed the previous clone-centric view for in situ data to a gene-centric view. This is possible because now we have linked all the data present in MEPD to the medaka gene annotation in ENSEMBL. In addition, we have also connected the medaka genes in MEPD to their corresponding orthologous gene in zebrafish, again using the ENSEMBL database. Based on this, we provide a link to the Zebrafish Model Organism Database (ZFIN) to allow researches to compare expression data between these two fish model organisms. As a second major improvement, we have modified the design of the database to enable it to host regulatory elements, promoters or enhancers, expression patterns in addition to gene expression. The combination of gene expression, by traditional in situ, and regulatory element expression, typically by fluorescence reporter gene, within the same platform assures consistency in terms of annotation. In our opinion, this will allow researchers to uncover new insights between the expression domain of genes and their regulatory landscape. PMID:26450962

  14. Nested transcripts of gap junction gene have distinct expression patterns.

    PubMed

    Zhang, Z; Curtin, K D; Sun, Y A; Wyman, R J

    1999-09-05

    The shaking B locus (shakB, or Passover) codes for structural molecules of gap junctions in Drosophila. This report describes the complex set of transcripts from the shakB locus. A nested set of five transcripts is described. The transcripts share 3' exons, but each has its own 5' exon. The transcripts are arrayed as a series in the genomic DNA stretching over 60 kb. The 5' end of each successive transcript lies further proximal on the chromosome. Each new transcript shares all the 3' exons with the one preceding it, but adds one or two more 5' exons. The different transcripts are expressed in a wide variety of locations in the nervous system and in non-neural tissues. Some tissues express more than one transcript, and the expression pattern of each is developmentally regulated. Within the adult central nervous system (CNS), these transcripts have an expression pattern that is restricted to the giant fiber system (GFS). The GFS is a small set of neurons which mediates the visually induced escape jump. shakB is required for function of the GFS electrical synapses. The transcript previously defined as active in the giant fiber is not, in fact, expressed in that cell. Instead, we find that another transcript, shakB(N3), and perhaps shakB(N4) as well, is expressed in the GFS; this transcript is not expressed elsewhere in the adult CNS. Two other transcripts, shakB(N1) and shakB(N2), are expressed in the optic lamina but not elsewhere in the CNS. This expression pattern explains the neurophysiological and behavioral defects in escape exhibited in mutants of shakB.

  15. Spatial pattern of receptor expression in the olfactory epithelium.

    PubMed Central

    Nef, P; Hermans-Borgmeyer, I; Artières-Pin, H; Beasley, L; Dionne, V E; Heinemann, S F

    1992-01-01

    A PCR-based strategy for amplifying putative receptors involved in murine olfaction was employed to isolate a member (OR3) of the seven-transmembrane-domain receptor superfamily. During development, the first cells that express OR3 appear adjacent to the wall of the telencephalic vesicle at embryonic day 10. The OR3 receptor is uniquely expressed in a subset of olfactory cells that have a characteristic bilateral symmetry in the adult olfactory epithelium. This receptor and its specific pattern of expression may serve a functional role in odor coding or, alternatively, may play a role in the development of the olfactory system. Images PMID:1384038

  16. Cytokeratin 19 expression patterns of dentigerous cysts and odontogenic keratocysts.

    PubMed

    Kamath, K P; Vidya, M

    2015-01-01

    Although numerous investigators have studied the pattern of keratin expression in different odontogenic cysts, the results have been variable. The present study was conducted to determine the pattern of expression of cytokeratin 19 (CK 19) in the epithelial lining of odontogenic keratocysts and dentigerous cysts. The epithelial layers showing expression of the epithelial marker CK 19 was determined by immunohistochemical methods in 15 tissue specimens each of histopathologically confirmed cases of dentigerous cysts and odontogenic keratocysts. Statistical analysis was done to compare the CK 19 expression between dentigerous cyst and odontogenic keratocyst using the Chi-square test. P < 0.05 was considered to be statistically significant. All specimens of dentigerous cysts were positive for CK 19 with 20% (3/15) of the specimens showing expression only in a single layer of the epithelium, 40% (6/15) of the specimens showing expression in more than one layer but not the entire thickness of the epithelium, and the remaining 40% (6/15) showing expression throughout the entire thickness of the epithelium. In the case of odontogenic keratocysts, 40% (6/15) of the specimens were negative for CK 19, 40% (6/15) of the specimens showed expression only in a single layer of the epithelium, and 20% (3/15) of the specimens showed expression in more than one layer, but not the entire thickness of the epithelium. The observed differences in CK 19 expression by the two lesions were statistically significant (P < 0.01). The differences in CK 19 expression by these cysts may be utilized as a diagnostic tool in differentiating between these two lesions.

  17. Differential Gene Expression from Genome-Wide Microarray Analyses Distinguishes Lohmann Selected Leghorn and Lohmann Brown Layers

    PubMed Central

    Habig, Christin; Geffers, Robert; Distl, Ottmar

    2012-01-01

    The Lohmann Selected Leghorn (LSL) and Lohmann Brown (LB) layer lines have been selected for high egg production since more than 50 years and belong to the worldwide leading commercial layer lines. The objectives of the present study were to characterize the molecular processes that are different among these two layer lines using whole genome RNA expression profiles. The hens were kept in the newly developed small group housing system Eurovent German with two different group sizes. Differential expression was observed for 6,276 microarray probes (FDR adjusted P-value <0.05) among the two layer lines LSL and LB. A 2-fold or greater change in gene expression was identified on 151 probe sets. In LSL, 72 of the 151 probe sets were up- and 79 of them were down-regulated. Gene ontology (GO) enrichment analysis accounting for biological processes evinced 18 GO-terms for the 72 probe sets with higher expression in LSL, especially those taking part in immune system processes and membrane organization. A total of 32 enriched GO-terms were determined among the 79 down-regulated probe sets of LSL. Particularly, these terms included phosphorus metabolic processes and signaling pathways. In conclusion, the phenotypic differences among the two layer lines LSL and LB are clearly reflected in their gene expression profiles of the cerebrum. These novel findings provide clues for genes involved in economically important line characteristics of commercial laying hens. PMID:23056453

  18. Profiling gene expression to distinguish the likely active diazotrophs from a sea of genetic potential in marine sediments

    PubMed Central

    Brown, S M; Jenkins, B D

    2014-01-01

    Nitrogen (N) cycling microbial communities in marine sediments are extremely diverse, and it is unknown whether this diversity reflects extensive functional redundancy. Sedimentary denitrifiers remove significant amounts of N from the coastal ocean and diazotrophs are typically regarded as inconsequential. Recently, N fixation has been shown to be a potentially important source of N in estuarine and continental shelf sediments. Analysis of expressed genes for nitrite reductase (nirS) and a nitrogenase subunit (nifH) was used to identify the likely active denitrifiers and nitrogen fixers in surface sediments from different seasons in Narragansett Bay (Rhode Island, USA). The overall diversity of diazotrophs expressing nifH decreased along the estuarine gradient from the estuarine head to an offshore continental shelf site. Two groups of sequences related to anaerobic sulphur/iron reducers and sulphate reducers dominated libraries of expressed nifH genes. Quantitative polymerase chain reaction (qPCR) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) data shows the highest abundance of both groups at a mid bay site, and the highest nifH expression at the head of the estuary, regardless of season. Several potential environmental factors, including water temperature, oxygen concentration and metal contamination, may influence the abundance and nifH expression of these two bacterial groups. PMID:24447468

  19. Enhancer trap expression patterns provide a novel teaching resource.

    PubMed

    Geisler, Matt; Jablonska, Barbara; Springer, Patricia S

    2002-12-01

    A collection of Arabidopsis enhancer trap transposants has been identified for use as a teaching tool. This collection serves to assist students in understanding the patterning and organization of plant tissues and cells, and will be useful in plant anatomy, morphology, and developmental biology courses. Each transposant exhibits reporter gene expression in a specific tissue, cell type, or domain, and these lines collectively offer a glimpse of compartments of gene expression. Some compartments correspond to classical definitions of botanical anatomy and can assist in anatomical identification. Other patterns of reporter gene expression are more complex and do not necessarily correspond to known anatomical features. The sensitivity of the beta-glucuronidase histochemical stain provides the student with a colorful and direct way to visualize difficult aspects of plant development and anatomy, and provides the teacher with an invaluable tool for a practical laboratory session.

  20. Expression pattern and clinical significance of DNA methyltransferase 3B variants in gastric carcinoma.

    PubMed

    Su, Xianwei; Lv, Chengyu; Qiao, Fengchang; Qiu, Xuemei; Huang, Wenbin; Wu, Qingxiang; Zhao, Zhujiang; Fan, Hong

    2010-03-01

    The aim of this study was to detect the expression pattern of DNA methyltransferase 3B (DNMT3B) variants in primary gastric cancer (GC) and to explore the clinical significance of DNMT3B variants in gastric carcinogenesis. Specific polymerase chain reaction (PCR) primer sets were designed to distinguish individual DNMT3B variants according to their splicing patterns. Expression levels of DNMT3B variants were assessed by quantitative real-time RT-PCR in gastric cancer tissue, normal gastric mucosae and GC cell lines. The relationship between the expression patterns of the DNMT3B variants and corresponding clinical information was analyzed by observing the expression levels of different variants in the tumors. These results demonstrate that DNMT3B overexpression is related to late phase invasion (P=0.029) and intestinal type (P=0.012) in GC. DNMT3B3 expression was higher in normal tissue, compared to tumor tissue (P=0.033). In contrast, only 18, 32 and 35% of the patient tumors overexpressed DNMT3B1, DNMT3B4 and DNMT3B5, respectively. While taking into account environmental factors (H. pylori, Epstein-Barr virus infection), H. pylori infection elevated DNMT3B1 and DNMT3B3 variants in tumors, while increasing DNMT3B4 in both tumor and non-cancerous tissues. Our findings indicated that the expression of DNMT3B3 is the major splice variant in normal gastric mucosae and may be affected by H. pylori infection. Elevated DNMT3B variants may influence the progression of gastric cancer and may possibly be a powerful indicator for the disease.

  1. On Expression Patterns and Developmental Origin of Human Brain Regions.

    PubMed

    Kirsch, Lior; Chechik, Gal

    2016-08-01

    Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions.

  2. On Expression Patterns and Developmental Origin of Human Brain Regions

    PubMed Central

    Kirsch, Lior; Chechik, Gal

    2016-01-01

    Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions. PMID:27564987

  3. Myeloid Cell Nuclear Differentiation Antigen (MNDA) Expression Distinguishes Extramedullary Presentations of Myeloid Leukemia From Blastic Plasmacytoid Dendritic Cell Neoplasm.

    PubMed

    Johnson, Ryan C; Kim, Jinah; Natkunam, Yasodha; Sundram, Uma; Freud, Aharon G; Gammon, Bryan; Cascio, Michael J

    2016-04-01

    Myeloid neoplasms constitute one of the most common malignancies in adults. In most cases these proliferations initially manifest in the blood and marrow; however, extramedullary involvement may precede blood or marrow involvement in a subset of cases, making a definitive diagnosis challenging by morphologic and immunohistochemical assessment alone. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive entity that frequently presents in extramedullary sites and can show morphologic and immunophenotypic overlap with myeloid neoplasms. Given that BPDCN and myeloid neoplasms may both initially present in extramedullary sites and that novel targeted therapies may be developed that exploit the unique molecular signature of BPDCN, new immunophenotypic markers that can reliably separate myeloid neoplasms from BPDCN are desirable. We evaluated the utility of myeloid cell nuclear differentiation antigen (MNDA) expression in a series of extramedullary myeloid leukemias (EMLs) and BPDCN. Forty biopsies containing EML and 19 biopsies containing BPDCN were studied by MNDA immunohistochemistry. The majority of myeloid neoplasms showed nuclear expression of MNDA (65%). In contrast, all cases of BPDCN lacked MNDA expression. These findings show that MNDA is expressed in the majority of EMLs and support the inclusion of MNDA immunohistochemistry in the diagnostic evaluation of blastic hematopoietic infiltrates, particularly when the differential diagnosis is between myeloid leukemia and BPDCN.

  4. A polynomial time biclustering algorithm for finding approximate expression patterns in gene expression time series

    PubMed Central

    Madeira, Sara C; Oliveira, Arlindo L

    2009-01-01

    Background The ability to monitor the change in expression patterns over time, and to observe the emergence of coherent temporal responses using gene expression time series, obtained from microarray experiments, is critical to advance our understanding of complex biological processes. In this context, biclustering algorithms have been recognized as an important tool for the discovery of local expression patterns, which are crucial to unravel potential regulatory mechanisms. Although most formulations of the biclustering problem are NP-hard, when working with time series expression data the interesting biclusters can be restricted to those with contiguous columns. This restriction leads to a tractable problem and enables the design of efficient biclustering algorithms able to identify all maximal contiguous column coherent biclusters. Methods In this work, we propose e-CCC-Biclustering, a biclustering algorithm that finds and reports all maximal contiguous column coherent biclusters with approximate expression patterns in time polynomial in the size of the time series gene expression matrix. This polynomial time complexity is achieved by manipulating a discretized version of the original matrix using efficient string processing techniques. We also propose extensions to deal with missing values, discover anticorrelated and scaled expression patterns, and different ways to compute the errors allowed in the expression patterns. We propose a scoring criterion combining the statistical significance of expression patterns with a similarity measure between overlapping biclusters. Results We present results in real data showing the effectiveness of e-CCC-Biclustering and its relevance in the discovery of regulatory modules describing the transcriptomic expression patterns occurring in Saccharomyces cerevisiae in response to heat stress. In particular, the results show the advantage of considering approximate patterns when compared to state of the art methods that require

  5. Patterns of fluorescent protein expression in Scleractinian corals.

    PubMed

    Gruber, David F; Kao, Hung-Teh; Janoschka, Stephen; Tsai, Julia; Pieribone, Vincent A

    2008-10-01

    Biofluorescence exists in only a few classes of organisms, with Anthozoa possessing the majority of species known to express fluorescent proteins. Most species within the Anthozoan subgroup Scleractinia (reef-building corals) not only express green fluorescent proteins, they also localize the proteins in distinct anatomical patterns.We examined the distribution of biofluorescence in 33 coral species, representing 8 families, from study sites on Australia's Great Barrier Reef. For 28 of these species, we report the presence of biofluorescence for the first time. The dominant fluorescent emissions observed were green (480-520 nm) and red (580-600 nm). Fluorescent proteins were expressed in three distinct patterns (highlighted, uniform, and complementary) among specific anatomical structures of corals across a variety of families. We report no significant overlap between the distribution of fluorescent proteins and the distribution of zooxanthellae. Analysis of the patterns of fluorescent protein distribution provides evidence that the scheme in which fluorescent proteins are distributed among the anatomical structures of corals is nonrandom. This targeted expression of fluorescent proteins in corals produces contrast and may function as a signaling mechanism to organisms with sensitivity to specific wavelengths of light.

  6. Tissue-Specific MicroRNA Expression Patterns in Four Types of Kidney Disease.

    PubMed

    Baker, Maria Angeles; Davis, Seth J; Liu, Pengyuan; Pan, Xiaoqing; Williams, Anna Marie; Iczkowski, Kenneth A; Gallagher, Sean T; Bishop, Kaylee; Regner, Kevin R; Liu, Yong; Liang, Mingyu

    2017-10-01

    MicroRNAs contribute to the development of kidney disease. Previous analyses of microRNA expression in human kidneys, however, were limited by tissue heterogeneity or the inclusion of only one pathologic type. In this study, we used laser-capture microdissection to obtain glomeruli and proximal tubules from 98 human needle kidney biopsy specimens for microRNA expression analysis using deep sequencing. We analyzed specimens from patients with diabetic nephropathy (DN), FSGS, IgA nephropathy (IgAN), membranoproliferative GN (MPGN) (n=19-23 for each disease), and a control group (n=14). Compared with control glomeruli, DN, FSGS, IgAN, and MPGN glomeruli exhibited differential expression of 18, 12, two, and 17 known microRNAs, respectively. The expression of several microRNAs also differed between disease conditions. Specifically, compared with control or FSGS glomeruli, IgAN glomeruli exhibited downregulated expression of hsa-miR-3182. Furthermore, in combination, the expression levels of hsa-miR-146a-5p and hsa-miR-30a-5p distinguished DN from all other conditions except IgAN. Compared with control proximal tubules, DN, FSGS, IgAN, and MPGN proximal tubules had differential expression of 13, 14, eight, and eight microRNAs, respectively, but expression of microRNAs did not differ significantly between the disease conditions. The abundance of several microRNAs correlated with indexes of renal function. Finally, we validated the differential glomerular expression of select microRNAs in a second cohort of patients with DN (n=19) and FSGS (n=21). In conclusion, we identified tissue-specific microRNA expression patterns associated with several kidney pathologies. The identified microRNAs could be developed as biomarkers of kidney diseases and might be involved in disease mechanisms. Copyright © 2017 by the American Society of Nephrology.

  7. Regional and developmental brain expression patterns of SNAP25 splice variants.

    PubMed

    Prescott, Gerald R; Chamberlain, Luke H

    2011-04-28

    SNAP25 is an essential SNARE protein for regulated exocytosis in neuronal cells. Differential splicing of the SNAP25 gene results in the expression of two transcripts, SNAP25a and SNAP25b. These splice variants differ by only 9 amino acids, and studies of their expression to date have been limited to analysis of the corresponding mRNAs. Although these studies have been highly informative, it is possible that factors such as differential turnover of the SNAP25 proteins could complicate interpretations based entirely on mRNA expression profiles. We report the generation and characterization of antibodies that distinguish between SNAP25a and SNAP25b isoforms, and their use to investigate the expression profile of these proteins in rat and human brain. In rat brain, SNAP25b protein expression increased dramatically during post-natal development, whereas the increase in SNAP25a expression was more modest and variable. The extent of this up-regulation in SNAP25b expression was similar across cortex, cerebellum and hippocampus. The SNAP25 isoforms also displayed distinct regional expression patterns, with SNAP25a very weakly expressed in both rat and human cerebellum. Quantitative analysis revealed that SNAP25b was the dominant isoform in all adult human brain regions examined. SNAP25a and SNAP25b display distinct developmental and regional expression profiles in rat and human brain. These differences might reflect distinct functions of these highly conserved isoforms in membrane fusion pathways in the brain. The antibodies generated and characterized in this study represent important tools for future analyses of these essential SNARE protein isoforms.

  8. Patterns of soybean proline-rich protein gene expression.

    PubMed Central

    Wyatt, R E; Nagao, R T; Key, J L

    1992-01-01

    The expression patterns of three members of a gene family that encodes proline-rich proteins in soybean (SbPRPs) were examined using in situ hybridization experiments. In most instances, the expression of SbPRP genes was intense in a limited number of cell types of a particular organ. SbPRP1 RNA was localized in several cell types of soybean hypocotyls, including cells within the phloem and xylem. SbPRP1 expression increased within epidermal cells in the elongating and mature regions of the hypocotyl; expression was detected also in lignified cells surrounding the hilum of mature seeds. SbPRP2 RNA was present in cortical cells and in the vascular tissue of the hypocotyl, especially cells of the phloem. This gene was expressed also in the inner integuments of the mature seed coat. SbPRP3 RNA was localized specifically to the endodermoid layer of cells surrounding the stele in the elongating region of the hypocotyl, as well as in the epidermal cells of leaves and cotyledons. These data show that members of this gene family exhibit cell-specific expression. The members of the SbPRP gene family are expressed in different types of cells and in some cell types that also express the glycine-rich protein or hydroxyproline-rich glycoprotein classes of genes. PMID:1525563

  9. High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival.

    PubMed

    Birks, Diane K; Donson, Andrew M; Patel, Purvi R; Dunham, Christopher; Muscat, Andrea; Algar, Elizabeth M; Ashley, David M; Kleinschmidt-Demasters, B K; Vibhakar, Rajeev; Handler, Michael H; Foreman, Nicholas K

    2011-12-01

    Molecular profiling of tumors has proven to be a valuable tool for identification of prognostic and diagnostic subgroups in medulloblastomas, glioblastomas, and other cancers. However, the molecular landscape of atypical teratoid/rhabdoid tumors (AT/RTs) remains largely unexplored. To address this issue, we used microarrays to measure the gene expression profiles of 18 AT/RTs and performed unsupervised hierarchical clustering to determine molecularly similar subgroups. Four major subgroups (clusters) were identified. These did not conform to sex, tumor location, or presence of monosomy 22. Clusters showed distinct gene signatures and differences in enriched biological processes, including elevated expression of some genes associated with choroid plexus lineage in cluster 4. In addition, survival differed significantly by cluster, with shortest survival (mean, 4.7 months) in both clusters 3 and 4, compared with clusters 1 and 2 (mean, 28.1 months). Analysis showed that multiple bone morphogenetic protein (BMP) pathway genes were upregulated in the short survival clusters, with BMP4 showing the most significant upregulation (270-fold). Thus, high expression of BMP pathway genes was negatively associated with survival in this dataset. Our study indicates that molecular subgroups exist in AT/RTs and that molecular profiling of these comparatively rare tumors may be of diagnostic, prognostic, and therapeutic value.

  10. Distinguishing cell type using epigenotype

    NASA Astrophysics Data System (ADS)

    Wytock, Thomas; Motter, Adilson E.

    Recently, researchers have proposed that unique cell types are attractors of their epigenetic dynamics including gene expression and chromatin conformation patterns. Traditionally, cell types have been classified by their function, morphology, cytochemistry, and other macroscopically observable properties. Because these properties are the result of many proteins working together, it should be possible to predict cell types from gene expression or chromatin conformation profiles. In this talk, I present a maximum entropy approach to identify and distinguish cell type attractors on the basis of correlations within these profiles. I will demonstrate the flexibility of this method through its separate application to gene expression and chromatin conformation datasets. I show that our method out-performs other machine-learning techniques and uncorrelated benchmarks. We adapt our method to predict growth rate from gene expression in E. coli and S. cerevisiae and compare our predictions with those from metabolic models. In addition, our method identifies a nearly convex region of state-space associated with each cell type attractor basin. Estimates of the growth rate and attractor basin make it possible to rationally control gene regulatory networks independent of a model. This research was supported by NSF-GRFP, NSF-GK12, GAANN, and Northwestern's NIH-NIGMS Molecular Biophysics Training Grant.

  11. Diagnostic value of CD10 and Bcl2 expression in distinguishing cutaneous basal cell carcinoma from squamous cell carcinoma and seborrheic keratosis.

    PubMed

    Gaballah, Mohammad A; Ahmed, Rehab-Allah

    2015-12-01

    The distinction between cutaneous basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and seborrheic keratosis (SK), which are common entities in clinical practice, can be difficult clinically and histologically. CD10 and Bcl2 antigens are important factors in tumor growth, survival and spread. The aim of the present study is to define the frequency of CD10 and Bcl2 expression in such cutaneous tumors and its relation to the clinicopathological characteristics as well as their possible diagnostic utility. CD10 and Bcl2 immunohistochemistry was performed on 30 BCC, 20 SCC and 15 SK. 93.3% of SK cases and 53.3% of BCC cases showed significant expression of CD10 in tumor cells when compared either with each other or with SCC cases (100% negative). Stromal CD10 expression was positive in 50% of BCC cases and 75% of SCC cases. Stromal CD10 expression was significantly higher in high risk BCC and BCC with infiltrating deep margins; furthermore, it showed a significant positive correlation with grade of SCC. A significant inverse correlation between CD10 expression in stromal and tumor cells of BCC was present. Bcl2 was significantly expressed in 93.3% of SK cases and 80% of BCC cases when compared with SCC cases (100% negative). It was found that for distinguishing BCC from SK, only CD10 expression in tumor cells provided a high diagnostic value with positive likelihood ratio (PLR) was 7.00. In addition, CD10 and Bcl2 expression in tumor cells could give convincing diagnostic value to distinguish SCC from SK (PLR=15.00 for each marker). Moreover, for differentiating BCC from SCC, only Bcl2 in the tumor cells could provide a high diagnostic value (PLR=5.5). In conclusion, CD10 and Bcl2 can help in differentiating cutaneous BCC from SK and SCC. The overexpression of CD10 in the stromal cells of SCC and some variants of BCC suggests the invasive properties of such tumors.

  12. Patterns of gene expression in developing embryos of Arabidopsis hybrids.

    PubMed

    Alonso-Peral, Maria M; Trigueros, Marina; Sherman, Bjorg; Ying, Hua; Taylor, Jennifer M; Peacock, William J; Dennis, Elizabeth S

    2017-03-01

    Hybrids between the Arabidopsis ecotypes C24 and Ler have high levels of hybrid vigour, or heterosis, in both biomass and seed yield. Heterosis can be detected throughout the development of the plant and in different tissues. We examined developing embryos and seeds of C24/Ler reciprocal hybrids with the aim of detecting the earliest time at which heterotic gene activity occurs. In the transcriptomes of 4-dap (days after pollination; dermatogen to globular) and 6-dap (heart) embryos from both parents and hybrids, 95% of expressed genes were at the mid parent value (MPV) and 95% of the genes with single nucleotide polymorphisms between C24 and Ler retained the same relative allelic expression levels in the hybrids as existed in the parents. This included loci that had equivalent levels of transcription in the two parents, together with loci which had different levels of expression in the parents. Amongst the genes which did not have MPV expression levels in the hybrids (non-additively expressed genes), approximately 40 in the globular embryo stage and 89 in the heart embryo stage had altered levels of transcription in both reciprocal hybrids; these genes could contribute to the heterotic phenotype of the hybrid embryo. Many of the non-additively expressed genes had expression levels that were shifted towards maternal levels of transcription, and these differed in the reciprocal hybrids. Allelic expression analysis indicated that most genes with altered allelic contributions in the hybrids had an increase in the expression level of the hybrid's maternal allele. Consistent with the maternal pattern of gene expression, embryo and seed also show maternally influenced phenotypes. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  13. Autophagy and lysosomal related protein expression patterns in human glioblastoma.

    PubMed

    Giatromanolaki, Alexandra; Sivridis, Efthimios; Mitrakas, Achileas; Kalamida, Dimitra; Zois, Christos E; Haider, Syed; Piperidou, Charitomeni; Pappa, Aglaia; Gatter, Kevin C; Harris, Adrian L; Koukourakis, Michael I

    2014-01-01

    Glioblastoma cells are resistant to apoptotic stimuli with autophagic death prevailing under cytotoxic stress. Autophagy interfering agents may represent a new strategy to test in combination with chemo-radiation. We investigated the patterns of expression of autophagy related proteins (LC3A, LC3B, p62, Beclin 1, ULK1 and ULK2) in a series of patients treated with post-operative radiotherapy. Experiments with glioblastoma cell lines (T98 and U87) were also performed to assess autophagic response under conditions simulating the adverse intratumoral environment. Glioblastomas showed cytoplasmic overexpression of autophagic proteins in a varying extent, so that cases could be grouped into low and high expression groups. 10/23, 5/23, 13/23, 5/23, 8/23 and 9/23 cases examined showed extensive expression of LC3A, LC3B, Beclin 1, Ulk 1, Ulk 2 and p62, respectively. Lysosomal markers Cathepsin D and LAMP2a, as well as the lyososomal biogenesis transcription factor TFEB were frequently overexpressed in glioblastomas (10/23, 11/23, and 10/23 cases, respectively). TFEB was directly linked with PTEN, Cathepsin D, HIF1α, LC3B, Beclin 1 and p62 expression. PTEN was also significantly related with LC3B but not LC3A expression, in both immunohistochemistry and gene expression analysis. Confocal microscopy in T98 and U87 cell lines showed distinct identity of LC3A and LC3B autophagosomes. The previously reported stone-like structure (SLS) pattern of LC3 expression was related with prognosis. SLS were inducible in glioblastoma cell lines under exposure to acidic conditions and 2DG mediated glucose antagonism. The present study provides the basis for autophagic characterization of human glioblastoma for further translational studies and targeted therapy trials.

  14. Aquaporin expression patterns in the developing mouse salivary gland.

    PubMed

    Larsen, Helga S; Ruus, Ann-Kristin; Galtung, Hilde Kanli

    2009-12-01

    Little is known about the presence of the various membrane-located water channels, aquaporins (AQP), during the prenatal and postnatal development of the mouse submandibular salivary gland (SMG). To learn more about AQPs in the developing aspect of salivary glands, we investigated trends in the expression patterns of several AQPs using the embryonic, early postnatal, and young adult mouse SMGs as models. We have chosen AQPs previously found in salivary glands in other animals. Transcripts of AQPs 1, 3, 4, 5, and 8 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and quantified. Aquaporin proteins 1, 3, 4, and 5, but not AQP protein 8, were detected and quantified using western blotting. The various AQPs showed distinct transcript and protein-expression patterns. The change in trends may indicate that the importance of the various AQPs varies throughout the developmental stages in the mouse SMG. Their presence might be related to cell adhesion, migration, proliferation, apoptosis, transepithelial transport, osmosensing, or cell volume regulation; all roles that in the literature are linked to the various AQPs. Overall, this study demonstrates that AQP presentation varies and has a specific expression pattern during the development of mouse SMG. This feature may be important for glandular anatomical and physiological development.

  15. Soybean kinome: functional classification and gene expression patterns.

    PubMed

    Liu, Jinyi; Chen, Nana; Grant, Joshua N; Cheng, Zong-Ming Max; Stewart, C Neal; Hewezi, Tarek

    2015-04-01

    The protein kinase (PK) gene family is one of the largest and most highly conserved gene families in plants and plays a role in nearly all biological functions. While a large number of genes have been predicted to encode PKs in soybean, a comprehensive functional classification and global analysis of expression patterns of this large gene family is lacking. In this study, we identified the entire soybean PK repertoire or kinome, which comprised 2166 putative PK genes, representing 4.67% of all soybean protein-coding genes. The soybean kinome was classified into 19 groups, 81 families, and 122 subfamilies. The receptor-like kinase (RLK) group was remarkably large, containing 1418 genes. Collinearity analysis indicated that whole-genome segmental duplication events may have played a key role in the expansion of the soybean kinome, whereas tandem duplications might have contributed to the expansion of specific subfamilies. Gene structure, subcellular localization prediction, and gene expression patterns indicated extensive functional divergence of PK subfamilies. Global gene expression analysis of soybean PK subfamilies revealed tissue- and stress-specific expression patterns, implying regulatory functions over a wide range of developmental and physiological processes. In addition, tissue and stress co-expression network analysis uncovered specific subfamilies with narrow or wide interconnected relationships, indicative of their association with particular or broad signalling pathways, respectively. Taken together, our analyses provide a foundation for further functional studies to reveal the biological and molecular functions of PKs in soybean. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  16. Characterization and expression pattern of the novel MIA homolog TANGO.

    PubMed

    Bosserhoff, A K; Moser, M; Buettner, R

    2004-07-01

    A novel human gene, TANGO, encoding a MIA ('melanoma inhibitory activity') homologous protein was identified by a gene bank search. TANGO, together with the homologous genes MIA, OTOR (FPD, MIAL) and MIA2 define a novel gene family sharing important structural features, significant homology at both the nucleotide and protein level, and similar genomic organization. The four members share 34-45% amino acid identity and 47-59% cDNA sequence identity. TANGO encodes a mature protein of 103 amino acids in addition to a hydrophobic secretory signal sequence. Sequence homology confirms the highly conserved SH3 structure present also in MIA, OTOR and MIA2. Thus, it appears that there are a number of extracellular proteins with SH3-fold like structures. Interestingly, in situ hybridization, RT-PCR and Northern Blots revealed very broad TANGO expression patterns in contrast to the highly restricted expression patterns previously determined for the other members of the MIA gene family. The only cells lacking TANGO expression are cells belonging to the hematopoetic system. High levels of TANGO expression were observed both during embryogenesis and in adult tissues.

  17. Gene expression patterns in glucose-stimulated podocytes

    SciTech Connect

    Han, Seung Hyeok; Yang, Sanghwa; Jung, Dong Sub; Li, Jin Ji; Kim, Jin Ju; Kwak, Seung Jae; Kim, Dong Ki; Moon, Sung Jin; Lee, Jung Eun; Han, Dae-Suk; Kang, Shin-Wook

    2008-06-06

    To explore the mechanisms of podocyte injury under diabetic conditions, we performed an expression profile in glucose-stimulated podocytes. Differential gene expression profiles between conditionally immortalized mouse podocytes cultured in medium containing 5.6 and 30 mM glucose were measured with oligonucleotide microarrays. Of the genes identified, heme oxygenase-1, vascular endothelial growth factor-A, and thrombospondin-1 showed a consistently increased pattern, whereas angiotensin-converting enzyme-2 and peroxisomal proliferator activator receptor-{gamma} were down-regulated. These results were validated using real-time PCR and western blotting in podocytes, and with immunohistochemistry on renal tissues from streptozotocin-induced diabetic rats. Not only is this the first report of gene expression profiling of podocyte injury under diabetic conditions, but the identified genes are promising targets for future diabetes research.

  18. Expression Pattern of Axin2 During Chicken Development

    PubMed Central

    Eckei, Gesa; Böing, Marion; Brand-Saberi, Beate; Morosan-Puopolo, Gabriela

    2016-01-01

    Canonical Wnt-signalling is well understood and has been extensively described in many developmental processes. The regulation of this signalling pathway is of outstanding relevance for proper development of the vertebrate and invertebrate embryo. Axin2 provides a negative-feedback-loop in the canonical Wnt-pathway, being a target gene and a negative regulator. Here we provide a detailed analysis of the expression pattern in the development of the chicken embryo. By performing in-situ hybridization on chicken embryos from stage HH 04+ to HH 32 we detected a temporally and spatially restricted dynamic expression of Axin2. In particular, data about the expression of Axin2 mRNA in early embryogenesis, somites, neural tube, limbs, kidney and eyes was obtained. PMID:27680024

  19. Genome-wide patterns of Arabidopsis gene expression in nature.

    PubMed

    Richards, Christina L; Rosas, Ulises; Banta, Joshua; Bhambhra, Naeha; Purugganan, Michael D

    2012-01-01

    Organisms in the wild are subject to multiple, fluctuating environmental factors, and it is in complex natural environments that genetic regulatory networks actually function and evolve. We assessed genome-wide gene expression patterns in the wild in two natural accessions of the model plant Arabidopsis thaliana and examined the nature of transcriptional variation throughout its life cycle and gene expression correlations with natural environmental fluctuations. We grew plants in a natural field environment and measured genome-wide time-series gene expression from the plant shoot every three days, spanning the seedling to reproductive stages. We find that 15,352 genes were expressed in the A. thaliana shoot in the field, and accession and flowering status (vegetative versus flowering) were strong components of transcriptional variation in this plant. We identified between ∼110 and 190 time-varying gene expression clusters in the field, many of which were significantly overrepresented by genes regulated by abiotic and biotic environmental stresses. The two main principal components of vegetative shoot gene expression (PC(veg)) correlate to temperature and precipitation occurrence in the field. The largest PC(veg) axes included thermoregulatory genes while the second major PC(veg) was associated with precipitation and contained drought-responsive genes. By exposing A. thaliana to natural environments in an open field, we provide a framework for further understanding the genetic networks that are deployed in natural environments, and we connect plant molecular genetics in the laboratory to plant organismal ecology in the wild.

  20. Rootstock effects on gene expression patterns in apple tree scions.

    PubMed

    Jensen, Philip J; Rytter, Jo; Detwiler, Elizabeth A; Travis, James W; McNellis, Timothy W

    2003-11-01

    Like many fruit trees, apple trees (Malus pumila) do not reproduce true-to-type from seed. Desirable cultivars are clonally propagated by grafting onto rootstocks that can alter the characteristics of the scion. For example, the M.7 EMLA rootstock is semi-dwarfing and reduces the susceptibility of the scion to Erwinia amylovora, the causal agent of fire blight disease. In contrast, the M.9 T337 rootstock is dwarfing and does not alter fire blight susceptibility of the scion. This study represents a comprehensive comparison of gene expression patterns in scions of the 'Gala' apple cultivar grafted to either M.7 EMLA or M.9 T337. Expression was determined by cDNA-AFLP coupled with silver staining of the gels. Scions grafted to the M.9 T337 rootstock showed higher expression of a number of photosynthesis-related, transcription/translation-related, and cell division-related genes, while scions grafted to the M.7 EMLA rootstock showed increased stress-related gene expression. The observed differences in gene expression showed a remarkable correlation with physiological differences between the two graft combinations. The roles that the differentially expressed genes might play in tree stature, stress tolerance, photosynthetic activity, fire blight resistance, and other differences conferred by the two rootstocks are discussed.

  1. Whole-mount in situ hybridization of sectioned tissues of species hybrids to detect cis-regulatory changes in gene expression pattern.

    PubMed

    Futahashi, Ryo

    2011-01-01

    To distinguish whether differences in gene expression between species or between individuals of the same species are caused by cis-regulatory changes or by distribution differences in trans-regulatory proteins, comparison of species-specific mRNA expression in an F1 hybrid by whole-mount in situ hybridization is a rarely used yet very powerful tool. If asymmetric expression pattern is observed for the two alleles, this implies a cis-regulatory divergence of this gene. Alternatively, if symmetric expression pattern is observed for both alleles, the change in expression of this gene is probably caused by changes in the distribution of trans-regulatory proteins. In this chapter, I describe how to prepare RNA probes, tissue samples and how to detect mRNA expression pattern using in situ hybridization. Although I choose to present here the detection of yellow-related gene (YRG) expression pattern in the larval epidermis of swallowtail butterflies, this protocol can be adapted to other species and tissues. YRG mRNA expression is correlated with interspecific differences of yellow and green larval color pattern such as V-shaped markings in swallowtail butterflies. F1 hybrids show an intermediate color pattern between parental species. In this case, both species-specific YRG mRNA showed a similar expression pattern in F1 hybrids, suggesting that the change in expression of YRG is mainly caused by changes in the distribution of trans-regulatory proteins.

  2. Integrative analysis of single nucleotide polymorphisms and gene expression efficiently distinguishes samples from closely related ethnic populations

    PubMed Central

    2012-01-01

    Background Ancestry informative markers (AIMs) are a type of genetic marker that is informative for tracing the ancestral ethnicity of individuals. Application of AIMs has gained substantial attention in population genetics, forensic sciences, and medical genetics. Single nucleotide polymorphisms (SNPs), the materials of AIMs, are useful for classifying individuals from distinct continental origins but cannot discriminate individuals with subtle genetic differences from closely related ancestral lineages. Proof-of-principle studies have shown that gene expression (GE) also is a heritable human variation that exhibits differential intensity distributions among ethnic groups. GE supplies ethnic information supplemental to SNPs; this motivated us to integrate SNP and GE markers to construct AIM panels with a reduced number of required markers and provide high accuracy in ancestry inference. Few studies in the literature have considered GE in this aspect, and none have integrated SNP and GE markers to aid classification of samples from closely related ethnic populations. Results We integrated a forward variable selection procedure into flexible discriminant analysis to identify key SNP and/or GE markers with the highest cross-validation prediction accuracy. By analyzing genome-wide SNP and/or GE markers in 210 independent samples from four ethnic groups in the HapMap II Project, we found that average testing accuracies for a majority of classification analyses were quite high, except for SNP-only analyses that were performed to discern study samples containing individuals from two close Asian populations. The average testing accuracies ranged from 0.53 to 0.79 for SNP-only analyses and increased to around 0.90 when GE markers were integrated together with SNP markers for the classification of samples from closely related Asian populations. Compared to GE-only analyses, integrative analyses of SNP and GE markers showed comparable testing accuracies and a reduced number

  3. Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.

    PubMed

    Otto, Benjamin; Gruner, Katharina; Heinlein, Christina; Wegwitz, Florian; Nollau, Peter; Ylstra, Bauke; Pantel, Klaus; Schumacher, Udo; Baumbusch, Lars O; Martin-Subero, José Ignacio; Siebert, Reiner; Wagener, Christoph; Streichert, Thomas; Deppert, Wolfgang; Tolstonog, Genrich V

    2013-03-15

    Mammary carcinomas developing in SV40 transgenic WAP-T mice arise in two distinct histological phenotypes: as differentiated low-grade and undifferentiated high-grade tumors. We integrated different types of information such as histological grading, analysis of aCGH-based gene copy number and gene expression profiling to provide a comprehensive molecular description of mammary tumors in WAP-T mice. Applying a novel procedure for the correlation of gene copy number with gene expression on a global scale, we observed in tumor samples a global coherence between genotype and transcription. This coherence can be interpreted as a matched transcriptional regulation inherited from the cells of tumor origin and determined by the activity of cancer driver genes. Despite common recurrent genomic aberrations, e.g. gain of chr. 15 in most WAP-T tumors, loss of chr. 19 frequently occurs only in low-grade tumors. These tumors show features of "basal-like" epithelial differentiation, particularly expression of keratin 14. The high-grade tumors are clearly separated from the low-grade tumors by strong expression of the Met gene and by coexpression of epithelial (e.g. keratin 18) and mesenchymal (e.g. vimentin) markers. In high-grade tumors, the expression of the nonmutated Met protein is associated with Met-locus amplification and Met activity. The role of Met as a cancer driver gene is supported by the contribution of active Met signaling to motility and growth of mammary tumor-derived cells. Finally, we discuss the independent origin of low- and high-grade tumors from distinct cells of tumor origin, possibly luminal progenitors, distinguished by Met gene expression and Met signaling. Copyright © 2012 UICC.

  4. CD1c-Related DCs that Express CD207/Langerin, but Are Distinguishable from Langerhans Cells, Are Consistently Present in Human Tonsils

    PubMed Central

    De Monte, Anne; Olivieri, Charles-Vivien; Vitale, Sébastien; Bailleux, Sonanda; Castillo, Laurent; Giordanengo, Valérie; Maryanski, Janet L.; Segura, Elodie; Doglio, Alain

    2016-01-01

    Several subsets of dendritic cells (DCs) are present in the oropharyngeal tonsillar tissues and are thought to behave as major actors in development and regulation of immunity by acting as a first line of recognition for airborne and alimentary antigens. We previously discovered in human adult tonsils infected with Epstein–Barr virus (EBV), a subset of DCs that expressed langerin/CD207, a lectin usually recognized as a hallmark of epidermal Langerhans cells (LCs). In the present study, we analyzed the content of several child and adult tonsils in order to characterize in more detail the phenotype of these tonsillar CD207-expressing DCs (tCD207 DCs) and to compare it with that of other human DC subsets. We showed that all the human tonsils studied (n = 12) contained significant proportions of tCD207 DCs among tonsillar cells expressing HLA-DR. Moreover, the presence of tCD207 DCs in tonsils from young children free of EBV infection indicated that these cells could be established early in the tonsil independently of EBV infection. We also showed that tCD207 DCs, that were found mainly located within the tonsillar lymphoid stroma, were distinguishable from LCs by the level of expression of CD1a and EpCAM, and also from human inflammatory DCs by the lack of CD1a, CD206, and CD14 expression. Detailed analysis of cell surface DC markers showed that tCD207 DCs were unrelated to CD141+ DCs or macrophages, but defined a subtype of tonsillar DCs closely related to myeloid resident CD1c DCs. Since it was established that blood CD1c myeloid DCs exhibit plasticity and are capable of expressing CD207 notably in the presence of inflammatory cytokines, it is tempting to speculate that CD207+ CD1c+ DCs may play a specific immune role. PMID:27252701

  5. CD1c-Related DCs that Express CD207/Langerin, but Are Distinguishable from Langerhans Cells, Are Consistently Present in Human Tonsils.

    PubMed

    De Monte, Anne; Olivieri, Charles-Vivien; Vitale, Sébastien; Bailleux, Sonanda; Castillo, Laurent; Giordanengo, Valérie; Maryanski, Janet L; Segura, Elodie; Doglio, Alain

    2016-01-01

    Several subsets of dendritic cells (DCs) are present in the oropharyngeal tonsillar tissues and are thought to behave as major actors in development and regulation of immunity by acting as a first line of recognition for airborne and alimentary antigens. We previously discovered in human adult tonsils infected with Epstein-Barr virus (EBV), a subset of DCs that expressed langerin/CD207, a lectin usually recognized as a hallmark of epidermal Langerhans cells (LCs). In the present study, we analyzed the content of several child and adult tonsils in order to characterize in more detail the phenotype of these tonsillar CD207-expressing DCs (tCD207 DCs) and to compare it with that of other human DC subsets. We showed that all the human tonsils studied (n = 12) contained significant proportions of tCD207 DCs among tonsillar cells expressing HLA-DR. Moreover, the presence of tCD207 DCs in tonsils from young children free of EBV infection indicated that these cells could be established early in the tonsil independently of EBV infection. We also showed that tCD207 DCs, that were found mainly located within the tonsillar lymphoid stroma, were distinguishable from LCs by the level of expression of CD1a and EpCAM, and also from human inflammatory DCs by the lack of CD1a, CD206, and CD14 expression. Detailed analysis of cell surface DC markers showed that tCD207 DCs were unrelated to CD141(+) DCs or macrophages, but defined a subtype of tonsillar DCs closely related to myeloid resident CD1c DCs. Since it was established that blood CD1c myeloid DCs exhibit plasticity and are capable of expressing CD207 notably in the presence of inflammatory cytokines, it is tempting to speculate that CD207(+) CD1c(+) DCs may play a specific immune role.

  6. Distinct patterns of sirtuin expression during progression of Alzheimer's disease.

    PubMed

    Lutz, Mirjam I; Milenkovic, Ivan; Regelsberger, Günther; Kovacs, Gabor G

    2014-06-01

    Aging is one of the major risk factors for Alzheimer's disease (AD). Sirtuins are associated with prolonged life span. To examine whether the expression levels of sirtuins associate with the progression of AD or not, we performed a comparative immunoblotting and immunohistochemical study of SIRT1, 3, and 5 in the entorhinal cortex and hippocampal subregions and white matter in 45 cases grouped according to Braak and Braak stages of neurofibrillary degeneration. In addition, we compared the expression levels with the local load of tau and amyloid-beta deposits, evaluated using morphometry. Our study revealed that (1) the neuronal subcellular redistribution of SIRT1 parallels the decrease in its expression, suggesting stepwise loss of neuroprotection dependent on the neuronal population; (2) in contrast to SIRT1 and 3, expression of SIRT5 increases during the progression of AD; (3) which might be related to its appearance in activated microglial cells. The complex patterns of the expression of sirtuins in relation to tissue damage should be taken into account when searching for therapies interacting with sirtuins.

  7. Expression Patterns of Atlantic Sturgeon (Acipenser oxyrinchus) During Embryonic Development

    PubMed Central

    Kaitetzidou, Elisavet; Ludwig, Arne; Gessner, Jörn; Sarropoulou, Elena

    2016-01-01

    During teleost ontogeny the larval and embryonic stages are key stages, since failure during this period of tissue differentiation may cause malformations, developmental delays, poor growth, and massive mortalities. Despite the rapid advances in sequencing technologies, the molecular backgrounds of the development of economically important but endangered fish species like the Atlantic sturgeon (Acipenser oxyrinchus) have not yet been thoroughly investigated. The current study examines the differential expression of transcripts involved in embryonic development of the Atlantic sturgeon. Addressing this goal, a reference transcriptome comprising eight stages was generated using an Illumina HiSequation 2500 platform. The constructed de novo assembly counted to 441,092 unfiltered and 179,564 filtered transcripts. Subsequently, the expression profile of four developmental stages ranging from early (gastrula) to late stages of prelarval development [2 d posthatching (dph)] were investigated applying an Illumina MiSeq platform. Differential expression analysis revealed distinct expression patterns among stages, especially between the two early and the two later stages. Transcripts upregulated at the two early stages were mainly enriched in transcripts linked to developmental processes, while transcripts expressed at the last two stages were mainly enriched in transcripts important to muscle contraction. Furthermore, important stage-specific expression has been detected for the hatching stage with transcripts enriched in molecule transport, and for the 2 dph stage with transcripts enriched in visual perception and lipid digestion. Our investigation represents a significant contribution to the understanding of Atlantic sturgeon embryonic development, and transcript characterization along with the differential expression results will significantly contribute to sturgeon research and aquaculture. PMID:27974440

  8. Interpulse interval in circulating growth hormone patterns regulates sexually dimorphic expression of hepatic cytochrome P450.

    PubMed Central

    Waxman, D J; Pampori, N A; Ram, P A; Agrawal, A K; Shapiro, B H

    1991-01-01

    Plasma growth hormone (GH) profiles are sexually differentiated in many species and regulate the sex-dependence of peripubescent growth rates and liver function, including steroid hydroxylase cytochrome P450 expression, by mechanisms that are poorly understood. By use of an external pump to deliver to hypophysectomized rats pulses of rat GH of varying frequency and amplitude, a critical element for liver discrimination between male and female GH patterns was identified. Liver expression of the male-specific steroid 2 alpha (or 16 alpha)-hydroxylase P450, designated CYP2C11, was stimulated by GH at both physiological and nonphysiological pulse amplitudes, durations, and frequencies, provided that an interpulse interval of no detectable GH was maintained for at least 2.5 hr. This finding suggests that hepatocytes undergo an obligatory recovery period after stimulation by a GH pulse. This period may be required to reset a GH-activated intracellular signaling pathway or may relate to the short-term absence of GH receptors at the hepatocyte surface after a cycle of GH binding and receptor internalization. These requirements were distinguished from those necessary for the stimulation by GH of normal male growth rates in hypophysectomized rats, indicating that different GH responses and, perhaps, different GH-responsive tissues recognize distinct signaling elements in the sexually dimorphic patterns of circulating GH. Images PMID:1862110

  9. Interpulse interval in circulating growth hormone patterns regulates sexually dimorphic expression of hepatic cytochrome P450.

    PubMed

    Waxman, D J; Pampori, N A; Ram, P A; Agrawal, A K; Shapiro, B H

    1991-08-01

    Plasma growth hormone (GH) profiles are sexually differentiated in many species and regulate the sex-dependence of peripubescent growth rates and liver function, including steroid hydroxylase cytochrome P450 expression, by mechanisms that are poorly understood. By use of an external pump to deliver to hypophysectomized rats pulses of rat GH of varying frequency and amplitude, a critical element for liver discrimination between male and female GH patterns was identified. Liver expression of the male-specific steroid 2 alpha (or 16 alpha)-hydroxylase P450, designated CYP2C11, was stimulated by GH at both physiological and nonphysiological pulse amplitudes, durations, and frequencies, provided that an interpulse interval of no detectable GH was maintained for at least 2.5 hr. This finding suggests that hepatocytes undergo an obligatory recovery period after stimulation by a GH pulse. This period may be required to reset a GH-activated intracellular signaling pathway or may relate to the short-term absence of GH receptors at the hepatocyte surface after a cycle of GH binding and receptor internalization. These requirements were distinguished from those necessary for the stimulation by GH of normal male growth rates in hypophysectomized rats, indicating that different GH responses and, perhaps, different GH-responsive tissues recognize distinct signaling elements in the sexually dimorphic patterns of circulating GH.

  10. Aberrant expression of the dendritic cell marker TNFAIP2 by the malignant cells of Hodgkin lymphoma and primary mediastinal large B-cell lymphoma distinguishes these tumor types from morphologically and phenotypically similar lymphomas.

    PubMed

    Kondratiev, Svetlana; Duraisamy, Sekhar; Unitt, Christine L; Green, Michael R; Pinkus, Geraldine S; Shipp, Margaret A; Kutok, Jeffery L; Drapkin, Ronny I; Rodig, Scott J

    2011-10-01

    Tumor necrosis factor-α-inducible protein-2 (TNFAIP2) is a protein upregulated in cultured cells treated with tumor necrosis factor α (TNF), but its expression in normal and neoplastic tissues remains largely unknown. Here, we use standard immunohistochemical techniques to demonstrate that TNFAIP2 is normally expressed by follicular dendritic cells, interdigitating dendritic cells, and macrophages but not by lymphoid cells in secondary lymphoid tissues. Consistent with this expression pattern, we found strong TNFAIP2 staining of tumor cells in 4 of 4 cases (100%) of follicular dendritic cell sarcoma and in 3 of 3 cases (100%) of histiocytic sarcoma. Although TNFAIP2 is not expressed by the small and intermediate-sized neoplastic B cells comprising follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, or marginal zone lymphoma, we observed strong TNFAIP2 staining of the large, neoplastic cells in 31 of 31 cases (100%) of classical Hodgkin lymphoma, in 12 of 12 cases (100%) of nodular lymphocyte-predominant Hodgkin lymphoma, and in 27 of 31 cases (87%) of primary mediastinal (thymic) large B-cell lymphoma. In contrast, TNFAIP2 was expressed by malignant cells in only 2 of 45 cases (4%) of diffuse large B-cell lymphoma, not otherwise specified, in 2 of 18 cases (11%) of Burkitt lymphoma, and in 1 of 19 cases (5%) of anaplastic large cell lymphoma. Further analysis indicates that TNFAIP2, as a single diagnostic marker, is more sensitive (sensitivity=87%) and specific (specificity=96%) than TRAF1, nuclear cRel, or CD23 for distinguishing the malignant B cells of primary mediastinal (thymic) large B-cell lymphoma from those of its morphologic and immunophenotypic mimic, diffuse large B-cell lymphoma, not otherwise specified. Thus, TNFAIP2 may serve as a useful new marker of dendritic and histiocytic sarcomas, the aberrant expression of which in the malignant cells of classical Hodgkin lymphoma and primary mediastinal (thymic) large B-cell lymphoma

  11. Distinct expression patterns of syndecans in the embryonic zebrafish brain.

    PubMed

    Hofmeister, Wolfgang; Devine, Christine A; Key, Brian

    2013-01-01

    Axon pathfinding in the neuroepithelium of embryonic brain is dependent on a variety of short and long range guidance cues. Heparan sulfate proteoglycans such as syndecans act as modulators of these cues and their importance in neural development is highlighted by their phylogenetic conservation. In Drosophilia, a single syndecan is present on the surface of axon growth cones and is required for chemorepulsive signalling during midline crossing. Understanding the role of syndecans in the vertebrate nervous system is challenging given that there are four homologous genes, syndecans 1-4. We show here that syndecans 2-4 are expressed in the zebrafish embryonic brain during the major period of axon growth. These genes show differing expression patterns in the brain which provides putative insights into their functional specificity.

  12. Quantification of spatiotemporal patterns of Ras isoform expression during development

    PubMed Central

    Newlaczyl, Anna U.; Coulson, Judy M.; Prior, Ian A.

    2017-01-01

    Ras proteins are important signalling hubs frequently dysregulated in cancer and in a group of developmental disorders called Rasopathies. Three Ras genes encode four proteins that differentially contribute to these phenotypes. Using quantitative real-time PCR (qRT-PCR) we have measured the gene expression profiles of each of the Ras isoforms in a panel of mouse tissues derived from a full developmental time course spanning embryogenesis through to adulthood. In most tissues and developmental stages we observe a relative contribution of KRas4B > > NRas ≥ KRas4A > HRas to total Ras expression with KRas4B typically representing 60–99% of all Ras transcripts. KRas4A is the most dynamically regulated Ras isoform with significant up-regulation of expression observed pre-term in stomach, intestine, kidney and heart. The expression patterns assist interpretation of the essential role of KRas in development and the preponderance of KRas mutations in cancer. PMID:28117393

  13. Matrix Gla Protein expression pattern in the early avian embryo.

    PubMed

    Correia, Elizabeth; Conceição, Natércia; Cancela, M Leonor; Belo, José A

    2016-01-01

    MGP (Matrix Gla Protein) is an extracellular matrix vitamin K dependent protein previously identified as a physiological inhibitor of calcification and shown to be well conserved among vertebrates during evolution. MGP is involved in other mechanisms such as TGF-β and BMP activity, and a proposed modulator of cell-matrix interactions. MGP is expressed early in vertebrate development although its role has not been clarified. Previous work in the chicken embryo found MGP localization predominantly in the aorta and aortic valve base, but no data is available earlier in development. Here we examined MGP expression pattern using whole-mount in situ hybridization and histological sectioning during the initial stages of chick development. MGP was first detected at HH10 in the head and in the forming dorsal aorta. At the moment of the onset of blood circulation, MGP was expressed additionally in the venous plexus which will remodel into the vitelline arteries. By E2.25, it is clear that the vitelline arteries are MGP positive. MGP expression progresses centrifugally throughout the area vasculosa of the yolk sac. Between stages HH17 and HH19 MGP is seen in the dorsal aorta, heart, notochord, nephric duct, roof plate, vitelline arteries and in the yolk sac, beneath main arterial branches and in the vicinity of several vessels and venules. MGP expression persists in these areas at least until E4.5. These data suggest that MGP expression could be associated with cell migration and differentiation and to the onset of angiogenesis in the developing chick embryo. This data has biomedical relevance by pointing to the potential use of chick embryo explants to study molecules involved in artery calcification.

  14. Patterns of gene expression in the murine brain revealed by in situ hybridization of brain-specific mRNAs.

    PubMed

    Branks, P L; Wilson, M C

    1986-07-01

    Biochemical differences between neuronal cell populations of the mammalian brain, including selection of neurotransmitters and distinct neural antigens, suggest that the regulation of gene expression plays an important role in defining brain function. Here we describe the use of in situ hybridization to identify cDNA clones of highly regulated mRNA species and to define directly their pattern of gene expression in brain at both gross morphological and cellular levels. One of the selected cDNA clones, pMuBr2, detected a single 3.0 kb mRNA species, which from in situ hybridization appears specific to oligodendroglia cells. Three other cDNA clones, pMuBr3, 8 and 85, identified polyadenylated mRNA transcripts expressed by neuronal cells of the murine brain. Viewed at the gross morphological level, the mRNAs hybridizing to these cDNA sequences exhibit different patterns of abundance distinguishing such brain structures as pons, anterior thalamus, hippocampus, basal ganglia and anterior lobe of the neuroendocrine pituitary gland. At the cellular level, in situ hybridization revealed that these mRNAs are differentially expressed by morphologically and functionally distinct neurons of the cerebellum and hippocampal formation. When examined in the context of known brain function, however, the regulated expression of the neuron-specific mRNAs does not correlate simply with known cellular morphology or previously demonstrated neuronal relationships suggesting novel patterns of gene expression which may contribute to brain function.

  15. Principal-Oscillation-Pattern Analysis of Gene Expression

    PubMed Central

    Wang, Daifeng; Arapostathis, Ari; Wilke, Claus O.; Markey, Mia K.

    2012-01-01

    Principal-oscillation-pattern (POP) analysis is a multivariate and systematic technique for identifying the dynamic characteristics of a system from time-series data. In this study, we demonstrate the first application of POP analysis to genome-wide time-series gene-expression data. We use POP analysis to infer oscillation patterns in gene expression. Typically, a genomic system matrix cannot be directly estimated because the number of genes is usually much larger than the number of time points in a genomic study. Thus, we first identify the POPs of the eigen-genomic system that consists of the first few significant eigengenes obtained by singular value decomposition. By using the linear relationship between eigengenes and genes, we then infer the POPs of the genes. Both simulation data and real-world data are used in this study to demonstrate the applicability of POP analysis to genomic data. We show that POP analysis not only compares favorably with experiments and existing computational methods, but that it also provides complementary information relative to other approaches. PMID:22253697

  16. SALL4 expression in gestational trophoblastic tumors: a useful tool to distinguish choriocarcinoma from placental site trophoblastic tumor and epithelioid trophoblastic tumor.

    PubMed

    Stichelbout, Morgane; Devisme, Louise; Franquet-Ansart, Hélène; Massardier, Jérôme; Vinatier, Denis; Renaud, Florence; Kerdraon, Olivier

    2016-08-01

    SALL4 has important functions in embryonic stem cells. The aim of this study was to investigate SALL4 expression in gestational trophoblastic neoplasia. We hypothesized that it could help to distinguish choriocarcinoma, the presumed most primitive form of gestational trophoblastic neoplasia, from placental site trophoblastic tumor and epithelioid trophoblastic tumor, which would be more differentiated variants. This study included 31 gestational trophoblastic neoplasias: 19 choriocarcinomas, 9 placental site trophoblastic tumors, 1 epithelioid trophoblastic tumor, and 2 mixed tumors comprising a placental site trophoblastic tumor and an epithelioid trophoblastic tumor. Unlike usual markers of gestational trophoblastic neoplasia (p63, human chorionic gonadotrophin and human placental lactogen), SALL4 was expressed in 100% of choriocarcinomas and it was not detected in any placental site trophoblastic tumor and epithelioid trophoblastic tumor. However, the proportion of positive cells varied in a wide range, from 10% to 70%, reflecting the fact that SALL4 was specifically present in mononuclear cells consistent with neoplastic cytotrophoblast. So, SALL4 may be helpful in the differential diagnosis of gestational trophoblastic neoplasias. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Genetic Networks and Anticipation of Gene Expression Patterns

    NASA Astrophysics Data System (ADS)

    Gebert, J.; Lätsch, M.; Pickl, S. W.; Radde, N.; Weber, G.-W.; Wünschiers, R.

    2004-08-01

    An interesting problem for computational biology is the analysis of time-series expression data. Here, the application of modern methods from dynamical systems, optimization theory, numerical algorithms and the utilization of implicit discrete information lead to a deeper understanding. In [1], we suggested to represent the behavior of time-series gene expression patterns by a system of ordinary differential equations, which we analytically and algorithmically investigated under the parametrical aspect of stability or instability. Our algorithm strongly exploited combinatorial information. In this paper, we deepen, extend and exemplify this study from the viewpoint of underlying mathematical modelling. This modelling consists in evaluating DNA-microarray measurements as the basis of anticipatory prediction, in the choice of a smooth model given by differential equations, in an approach of the right-hand side with parametric matrices, and in a discrete approximation which is a least squares optimization problem. We give a mathematical and biological discussion, and pay attention to the special case of a linear system, where the matrices do not depend on the state of expressions. Here, we present first numerical examples.

  18. Distinguishing Radiculopathies from Mononeuropathies

    PubMed Central

    Robblee, Jennifer; Katzberg, Hans

    2016-01-01

    Identifying “where is the lesion” is particularly important in the approach to the patient with focal dysfunction where a peripheral localization is suspected. This article outlines a methodical approach to the neuromuscular patient in distinguishing focal neuropathies versus radiculopathies, both of which are common presentations to the neurology clinic. This approach begins with evaluation of the sensory examination to determine whether there are irritative or negative sensory signs in a peripheral nerve or dermatomal distribution. This is followed by evaluation of deep tendon reflexes to evaluate if differential hyporeflexia can assist in the two localizations. Finally, identification of weak muscle groups unique to a nerve or myotomal pattern in the proximal and distal extremities can most reliably assist in a precise localization. The article concludes with an application of the described method to the common scenario of distinguishing radial neuropathy versus C7 radiculopathy in the setting of a wrist drop and provides additional examples for self-evaluation and reference. PMID:27468275

  19. Expression Patterns of Extracellular Matrix Proteins during Posterior Commissure Development

    PubMed Central

    Stanic, Karen; Saldivia, Natalia; Förstera, Benjamín; Torrejón, Marcela; Montecinos, Hernán; Caprile, Teresa

    2016-01-01

    Extracellular matrix (ECM) molecules are pivotal for central nervous system (CNS) development, facilitating cell migration, axonal growth, myelination, dendritic spine formation, and synaptic plasticity, among other processes. During axon guidance, the ECM not only acts as a permissive or non-permissive substrate for navigating axons, but also modulates the effects of classical guidance cues, such as netrin or Eph/ephrin family members. Despite being highly important, little is known about the expression of ECM molecules during CNS development. Therefore, this study assessed the molecular expression patterns of tenascin, HNK-1, laminin, fibronectin, perlecan, decorin, and osteopontin along chick embryo prosomere 1 during posterior commissure development. The posterior commissure is the first transversal axonal tract of the embryonic vertebrate brain. Located in the dorso-caudal portion of prosomere 1, posterior commissure axons primarily arise from the neurons of basal pretectal nuclei that run dorsally to the roof plate midline, where some turn toward the ipsilateral side. Expressional analysis of ECM molecules in this area these revealed to be highly arranged, and molecule interactions with axon fascicles suggested involvement in processes other than structural support. In particular, tenascin and the HNK-1 epitope extended in ventro-dorsal columns and enclosed axons during navigation to the roof plate. Laminin and osteopontin were expressed in the midline, very close to axons that at this point must decide between extending to the contralateral side or turning to the ipsilateral side. Finally, fibronectin, decorin, and perlecan appeared unrelated to axonal pathfinding in this region and were instead restricted to the external limiting membrane. In summary, the present report provides evidence for an intricate expression of different extracellular molecules that may cooperate in guiding posterior commissure axons. PMID:27733818

  20. Planarian Hox genes: novel patterns of expression during regeneration.

    PubMed

    Bayascas, J R; Castillo, E; Muñoz-Mármol, A M; Saló, E

    1997-01-01

    Platyhelminthes are widely considered to be the sister group of coelomates (Philippe, H., Chenuil, A. and Adoutte, A. (1994)Development 1994 Supplement, 15-24) and the first organisms to show bilateral symmetry and cephalization. Within this phylum, the freshwater planarians (Turbellaria, Tricladida) have been used as model systems for studying bidirectional regeneration (Slack, J. M. W. (1980) J. Theor. Biol 82, 105-140). We have been attempting to identify potential pattern-control genes involved in the regeneration of planarian heads and tails after amputation. Since Hox cluster genes determine positional identity along the anteroposterior axis in a wide range of animals (Slack, J. M. W., Holland, P. W. H. and Graham, C. F. (1993) Nature 361,490-492), we performed an extensive search for Hox-related genes in the planarian Dugesia(G)tigrina. Sequence analyses of seven planarian Dthox genes (Dthox-A to Dthox-G) reveal high similarities with the homeodomain region of the Hox cluster genes, allowing us to assign planarian Dthox genes to anterior and medial Hox cluster paralogous groups. Whole-mount in situ hybridization studies in regenerating adults showed very early, synchronous and colocalized activation of Dthox-D, Dthox-A, Dthox-C, Dthox-E, Dthox-G and Dthox-F. After one hour of regeneration a clear expression was observed in all Dthox genes studied. In addition, all seemed to be expressed in the same regenerative tissue, although in the last stages of regeneration (9 to 15 days) a differential timing of deactivation was observed. The same Dthox genes were also expressed synchronously and were colocalized during intercalary regeneration, although their expression was delayed. Terminal regeneration showed identical Dthox gene expression in anterior and posterior blastemas, which may prevent these genes from directing the distinction between head and tail. Finally, continuous expression along the whole lateral blastema in sagittal regenerates reflected a

  1. Pathologic patterns of interleukin 10 expression – A review

    PubMed Central

    Miller, Larisa; Debeljak, Željko; Horvat, Vesna

    2015-01-01

    Interleukin 10 (IL-10) is important pleiotropic immunoregulatory cytokine which gene is located on chromosome 1 at 1q31-32. There are many genetic variants of IL-10 gene. However, the most studied are two dinucleotide repeats (microsatellites), IL10.G and IL10.R, located 1.2 kb and 4 kb upstream of the transcription start site and three single nucleotide polymorphisms (SNPs) -1082(G/A), -819(C/T) and -592(C/A). A large number of studies have shown that IL-10 gene polymorphisms are associated with different diseases and play an important role in pathophysiology and clinical course of these diseases. This review summarizes published literature knowledge about the association of IL-10 polymorphisms and expression patterns with asthma, systemic lupus erythematosus, psoriasis, inflammatory bowel disease, rheumatoid arthritis, tuberculosis and some neoplasms. PMID:25672465

  2. Alterations in the immunohistochemical expression of Das-1 and CG-3 in colonic mucosal biopsy specimens helps distinguish ulcerative colitis from Crohn disease and from other forms of colitis.

    PubMed

    Yantiss, Rhonda K; Das, Kiron M; Farraye, Francis A; Odze, Robert D

    2008-06-01

    Distinction between ulcerative colitis (UC) and Crohn disease (CD) in mucosal biopsies is often difficult. Das-1 and CG-3 are monoclonal antibodies directed against an unknown colonic epithelial protein and human tropomyosin isoform-5, respectively, both show altered expression in patients with UC. In this study, we evaluated the utility of Das-1 and CG-3 in distinguishing UC from CD and from other types of colitis. One colonic biopsy specimen from each of 85 patients with confirmed UC (n=25), CD (n=15), lymphocytic (n=15), collagenous (n=15), and ischemic (n=15) colitis, and also 10 samples from normal controls, were stained for Das-1 and CG-3 using standard techniques. Reactivity for Das-1 and CG-3 was noted to be absent or present, and the location (ie, surface+/-crypt epithelium) and degree (weak or strong) of CG-3 staining was recorded. Loss of Das-1 staining occurred more frequently in UC (96%) compared with CD (20%), lymphocytic (20%), collagenous (13%), and ischemic colitis (0%) cases, as well as controls (10%, P<0.001 for all comparisons). CG-3 positivity in crypt epithelium was significantly more common in UC (52%) compared with the other groups (P< or =0.02 for all comparisons). The combination of strong crypt CG-3 staining and loss of Das-1 staining was noted in 44% of UC cases, but not in any other type of colitis (P=0.003 for all comparisons). We conclude that the patterns of Das-1 and CG-3 staining in colonic mucosal biopsies may be clinically useful in distinguishing UC from CD and from other colitidies.

  3. Signature MicroRNA expression patterns identified in humans with 22q11.2 deletion/DiGeorge syndrome

    PubMed Central

    de la Morena, M. Teresa; Eitson, Jennifer L.; Dozmorov, Igor M.; Belkaya, Serkan; Hoover, Ashley R.; Anguiano, Esperanza; Pascual, M. Virginia; van Oers, Nicolai S.C.

    2013-01-01

    Patients with 22q11.2 deletion syndrome have heterogeneous clinical presentations including immunodeficiency, cardiac anomalies, and hypocalcemia. The syndrome arises from hemizygous deletions of up to 3 Mb on chromosome 22q11.2, a region that contains 60 genes and 4 microRNAs. MicroRNAs are important post-transcriptional regulators of gene expression, with mutations in several microRNAs causal to specific human diseases. We characterized the microRNA expression patterns in the peripheral blood of patients with 22q11.2 deletion syndrome (n=31) compared to normal controls (n=22). Eighteen microRNAs had a statistically significant differential expression (p<0.05), with miR-185 expressed at 0.4× normal levels. The 22q11.2 deletion syndrome cohort exhibited microRNA expression hyper-variability and group dysregulation. Selected microRNAs distinguished patients with cardiac anomalies, hypocalcemia, and/or low circulating T cell counts. In summary, microRNA profiling of chromosome 22q11.2 deletion syndrome/DiGeorge patients revealed a signature microRNA expression pattern distinct from normal controls with clinical relevance. PMID:23454892

  4. Signature MicroRNA expression patterns identified in humans with 22q11.2 deletion/DiGeorge syndrome.

    PubMed

    de la Morena, M Teresa; Eitson, Jennifer L; Dozmorov, Igor M; Belkaya, Serkan; Hoover, Ashley R; Anguiano, Esperanza; Pascual, M Virginia; van Oers, Nicolai S C

    2013-04-01

    Patients with 22q11.2 deletion syndrome have heterogeneous clinical presentations including immunodeficiency, cardiac anomalies, and hypocalcemia. The syndrome arises from hemizygous deletions of up to 3Mb on chromosome 22q11.2, a region that contains 60 genes and 4 microRNAs. MicroRNAs are important post-transcriptional regulators of gene expression, with mutations in several microRNAs causal to specific human diseases. We characterized the microRNA expression patterns in the peripheral blood of patients with 22q11.2 deletion syndrome (n=31) compared to normal controls (n=22). Eighteen microRNAs had a statistically significant differential expression (p<0.05), with miR-185 expressed at 0.4× normal levels. The 22q11.2 deletion syndrome cohort exhibited microRNA expression hyper-variability and group dysregulation. Selected microRNAs distinguished patients with cardiac anomalies, hypocalcemia, and/or low circulating T cell counts. In summary, microRNA profiling of chromosome 22q11.2 deletion syndrome/DiGeorge patients revealed a signature microRNA expression pattern distinct from normal controls with clinical relevance.

  5. Spatial and temporal gene expression patterns occur during corm development.

    PubMed

    de Castro, L A; Carneiro, M; Neshich, D de C; de Paiva, G R

    1992-12-01

    We investigated gene expression patterns that occur during taro corm development. Two-dimensional gel electrophoresis identified several different prevalent proteins that accumulate during corm development. Microsequencing studies indicated that some of these proteins are related to taste-modifying proteins, such as curculin and miraculin, and proteins found in other storage organs, such as sporamin and the Kunitz trypsin inhibitor. A curculin-encoding cDNA clone, designated as TC1, was identified that corresponds to a highly prevalent 1-kb corm mRNA. The TC1 mRNA accumulates during corm development, is more prevalent in corm apical than basal regions, and is either absent, or present at low concentrations, in other vegetative organs such as the leaf and root. In situ hybridization experiments showed that the TC1 mRNA is highly concentrated in corm storage parenchyma cells and is absent, or present in reduced concentrations, in other corm cells and tissues. Our results show that corm development is associated with the differentiation of specialized cells and tissues, and that these differentiation events are coupled with the temporal and spatial expression of corm-specific genes.

  6. Spatial and temporal gene expression patterns occur during corm development.

    PubMed Central

    de Castro, L A; Carneiro, M; Neshich, D de C; de Paiva, G R

    1992-01-01

    We investigated gene expression patterns that occur during taro corm development. Two-dimensional gel electrophoresis identified several different prevalent proteins that accumulate during corm development. Microsequencing studies indicated that some of these proteins are related to taste-modifying proteins, such as curculin and miraculin, and proteins found in other storage organs, such as sporamin and the Kunitz trypsin inhibitor. A curculin-encoding cDNA clone, designated as TC1, was identified that corresponds to a highly prevalent 1-kb corm mRNA. The TC1 mRNA accumulates during corm development, is more prevalent in corm apical than basal regions, and is either absent, or present at low concentrations, in other vegetative organs such as the leaf and root. In situ hybridization experiments showed that the TC1 mRNA is highly concentrated in corm storage parenchyma cells and is absent, or present in reduced concentrations, in other corm cells and tissues. Our results show that corm development is associated with the differentiation of specialized cells and tissues, and that these differentiation events are coupled with the temporal and spatial expression of corm-specific genes. PMID:1467653

  7. Expression and methylation pattern of p16 in neuroblastoma tumorigenesis.

    PubMed

    Aktas, Safiye; Celebiler, Aydan Cavusoglu; Zadeoğlulari, Zeynep; Diniz, Gulden; Kargi, Aydanur; Olgun, Nur

    2010-03-01

    Understanding migration, population and differentiation of primordial neural crest cells will help in evolving biology of neuroblastoma. P16 is a tumour suppressor gene contributing in cell cycle arrest as cyclin dependent kinase inhibitor. Methylation is an important mechanism for silencing tumor suppressor genes. The aim of this study was to evaluate the role of p16 and its methylation pattern in neuroblastoma tumorigenesis. This study included 23 cases (11 male; 12 female) and 31 samples from archival paraffin embedded tissues. P16 was studied in 5 samples of normal adrenal medullar tissue, 5 samples of adrenal tissue including blastic rests, 5 samples of neuroblastoma in situ tissue and in 8 samples of neuroblastoma tissues primary and after chemotherapy in each group. The adrenal gland tissues were obtained from paediatric autopsy cases. Expression of p16 was searched by immunohistochemistry. Methylation specific PCR was used to detect the methylation rate of p16. The age range of autopsy cases was between 20 weeks of foetal age and 36 months of infant age. The mean age of neuroblastoma cases was 45 months. P16 expression was positive in normal adrenal tissues, in one of 5 samples of adrenal blastic rest tissue and in all of samples of after chemotherapy; while no expression was observed in neuroblastoma and neuroblastoma in situ tissues. P16 methylation was observed in samples of neuroblastoma in situ and primary neuroblastoma tissues. Our results suggest that p16 and its methylation seems to play role in neuroblastoma tumorigenesis and in the migration, population and differentiation of primordial neural crest cells. Inhibitors of DNA methylation may provide a useful tool for restoring p16 activity in neuroblastoma treatment.

  8. Patterns of Transposable Element Expression and Insertion in Cancer

    PubMed Central

    Clayton, Evan A.; Wang, Lu; Rishishwar, Lavanya; Wang, Jianrong; McDonald, John F.; Jordan, I. King

    2016-01-01

    Human transposable element (TE) activity in somatic tissues causes mutations that can contribute to tumorigenesis. Indeed, TE insertion mutations have been implicated in the etiology of a number of different cancer types. Nevertheless, the full extent of somatic TE activity, along with its relationship to tumorigenesis, have yet to be fully explored. Recent developments in bioinformatics software make it possible to analyze TE expression levels and TE insertional activity directly from transcriptome (RNA-seq) and whole genome (DNA-seq) next-generation sequence data. We applied these new sequence analysis techniques to matched normal and primary tumor patient samples from the Cancer Genome Atlas (TCGA) in order to analyze the patterns of TE expression and insertion for three cancer types: breast invasive carcinoma, head and neck squamous cell carcinoma, and lung adenocarcinoma. Our analysis focused on the three most abundant families of active human TEs: Alu, SVA, and L1. We found evidence for high levels of somatic TE activity for these three families in normal and cancer samples across diverse tissue types. Abundant transcripts for all three TE families were detected in both normal and cancer tissues along with an average of ~80 unique TE insertions per individual patient/tissue. We observed an increase in L1 transcript expression and L1 insertional activity in primary tumor samples for all three cancer types. Tumor-specific TE insertions are enriched for private mutations, consistent with a potentially causal role in tumorigenesis. We used genome feature analysis to investigate two specific cases of putative cancer-causing TE mutations in further detail. An Alu insertion in an upstream enhancer of the CBL tumor suppressor gene is associated with down-regulation of the gene in a single breast cancer patient, and an L1 insertion in the first exon of the BAALC gene also disrupts its expression in head and neck squamous cell carcinoma. Our results are consistent with

  9. Protein expression pattern of human MIER1 alpha, a novel estrogen receptor binding protein

    PubMed Central

    McCarthy, Patti L.; Paterno, Gary D.; Gillespie, Laura L.

    2014-01-01

    MIER1 is a transcriptional regulator that exists as several isoforms. Of particular interest is the MIER1α isoform, which contains in its unique C-terminus an LXXLL motif for interaction with nuclear hormone receptors. Indeed, MIER1α has been shown to interact with ERα and inhibit estrogen-stimulated growth of breast carcinoma cells. Moreover, the subcellular localization of MIER1α changes dramatically, from nuclear to cytoplasmic, during progression to invasive breast carcinoma. While human MIER1 RNA and protein expression pattern data have been posted on several websites, none of these studies use probes or antibodies that distinguish between the α and β isoforms. We report here the first immunohistochemical study of the MIER1α protein expression pattern in human tissues. Our analysis revealed intense staining of specific cell types within virtually every endocrine and reproductive tissue except for the thyroid gland. In particular, we detected intense staining of ovarian follicles and germinal epithelium, ductal epithelial cells of the breast, pancreatic islet cells, all areas of the anterior pituitary and all zones of the adrenal cortex; moderate staining of germ cells and Leydig cells within the testis, patches of chromaffin cells in the adrenal medulla and weak staining of the fibromuscular stroma within the prostate. Immunoreactivity was limited to the cytoplasm in all positive cells except for oocytes and germinal epithelial cells in which the nucleus was also stained and in ductal epithelial cells of the breast in which staining was exclusively nuclear. In general, non-endocrine tissues were negative, however a few exceptions were noted. These included hepatocytes, myocardial fibers and neurons in all regions of the brain examined, with the exception of the thalamus. Neuronal staining was restricted to the cell bodies and dendrites, as most axons were negative. These data suggest that human MIER1α functions specifically in endocrine tissues and in

  10. The E4 protein; structure, function and patterns of expression

    SciTech Connect

    Doorbar, John

    2013-10-15

    }E4, these kinases regulate one of the E1{sup ∧}E4 proteins main functions, the association with the cellular keratin network, and eventually also its cleavage by the protease calpain which allows assembly into amyloid-like fibres and reorganisation of the keratin network. Although the E4 proteins of different HPV types appear divergent at the level of their primary amino acid sequence, they share a recognisable modular organisation and pattern of expression, which may underlie conserved functions and regulation. Assembly into higher-order multimers and suppression of cell proliferation are common to all E4 proteins examined. Although not yet formally demonstrated, a role in virus release and transmission remains a likely function for E4. - Highlights: • E4 gene products have a modular structure, and are expressed from the E1{sup ∧}E4 spliced mRNA. • E4 proteins are modified during epithelial differentiation by phosphorylation and proteolysis. • The E4 proteins contribute to genome amplification-efficiency and virus synthesis. • E4 proteins are abundantly expressed and may facilitate efficient virus release and transmission. • High-risk E4 proteins are deposited as amyloid fibres and can be used as infection biomarkers.

  11. Rheumatoid Arthritis with Deficiency Pattern in Traditional Chinese Medicine Shows Correlation with Cold and Hot Patterns in Gene Expression Profiles

    PubMed Central

    Chen, Gao; Lu, Cheng; Xiao, Cheng; Niu, Xuyan; He, Xiaojuan; Jiang, Miao; Lu, Aiping

    2013-01-01

    In our precious study, the correlation between cold and hot patterns in traditional Chinese medicine (TCM) and gene expression profiles in rheumatoid arthritis (RA) has been explored. Based on TCM theory, deficiency pattern is another key pattern diagnosis among RA patients, which leads to a specific treatment principle in clinical management. Therefore, a further analysis was performed aiming at exploring the characteristic gene expression profile of deficiency pattern and its correlation with cold and hot patterns in RA patients by bioinformatics analysis approach based on gene expression profiles data detected with microarray technology. The TCM deficiency pattern-related genes network comprises 7 significantly, highly connected regions which are mainly involved in protein transcription processes, protein ubiquitination, toll-like receptor activated NF-κB regulated gene transcription and apoptosis, RNA clipping, NF-κB signal, nucleotide metabolism-related apoptosis, and immune response processes. Toll-like receptor activated NF-κB regulated gene transcription and apoptosis pathways are potential specific pathways related to TCM deficiency patterns in RA patients; TCM deficiency pattern is probably related to immune response. Network analysis can be used as a powerful tool for detecting the characteristic mechanism related to specific TCM pattern and the correlations between different patterns. PMID:24174973

  12. Distinct patterns of gene and protein expression elicited by organophosphorus pesticides in Caenorhabditis elegans

    PubMed Central

    Lewis, John A; Szilagyi, Maria; Gehman, Elizabeth; Dennis, William E; Jackson, David A

    2009-01-01

    Background The wide use of organophosphorus (OP) pesticides makes them an important public health concern. Persistent effects of exposure and the mechanism of neuronal degeneration are continuing issues in OP toxicology. To elucidate early steps in the mechanisms of OP toxicity, we studied alterations in global gene and protein expression in Caenorhabditis elegans exposed to OPs using microarrays and mass spectrometry. We tested two structurally distinct OPs (dichlorvos and fenamiphos) and employed a mechanistically different third neurotoxicant, mefloquine, as an out-group for analysis. Treatment levels used concentrations of chemical sufficient to prevent the development of 10%, 50% or 90% of mid-vulval L4 larvae into early gravid adults (EGA) at 24 h after exposure in a defined, bacteria-free medium. Results After 8 h of exposure, the expression of 87 genes responded specifically to OP treatment. The abundance of 34 proteins also changed in OP-exposed worms. Many of the genes and proteins affected by the OPs are expressed in neuronal and muscle tissues and are involved in lipid metabolism, cell adhesion, apoptosis/cell death, and detoxification. Twenty-two genes were differentially affected by the two OPs; a large proportion of these genes encode cytochrome P450s, UDP-glucuronosyl/UDP-glucosyltransferases, or P-glycoproteins. The abundance of transcripts and the proteins they encode were well correlated. Conclusion Exposure to OPs elicits a pattern of changes in gene expression in exposed worms distinct from that of the unrelated neurotoxicant, mefloquine. The functional roles and the tissue location of the genes and proteins whose expression is modulated in response to exposure is consistent with the known effects of OPs, including damage to muscle due to persistent hypercontraction, neuronal cell death, and phase I and phase II detoxification. Further, the two different OPs evoked distinguishable changes in gene expression; about half the differences are in

  13. Anatomic patterning in the expression of vestibulosympathetic reflexes

    NASA Technical Reports Server (NTRS)

    Kerman, I. A.; Yates, B. J.; McAllen, R. M.

    2000-01-01

    To investigate the possibility that expression of vestibulosympathetic reflexes (VSR) is related to a nerve's anatomic location rather than its target organ, we compared VSR recorded from the same type of postganglionic fiber [muscle vasoconstrictor (MVC)] located at three different rostrocaudal levels: hindlimb, forelimb, and face. Experiments were performed on chloralose-anesthetized cats, and vestibular afferents were stimulated electrically. Single MVC unit activity was extracted by spike shape analysis of few-fiber recordings, and unit discrimination was confirmed by autocorrelation. Poststimulus time histogram analysis revealed that about half of the neurons were initially inhibited by vestibular stimulation (type 1 response), whereas the other MVC fibers were initially strongly excited (type 2 response). MVC units with types 1 and 2 responses were present in the same nerve fascicle. Barosensitivity was equivalent in the two groups, but fibers showing type 1 responses fired significantly faster than those giving type 2 responses (0.29 +/- 0.04 vs. 0.20 +/- 0.02 Hz). Nerve fibers with type 1 responses were most common in the hindlimb (21 of 29 units) and least common in the face (2 of 11 units), the difference in relative proportion being significant (P < 0.05, chi(2) test). These results support the hypothesis that VSR are anatomically patterned.

  14. Anatomic patterning in the expression of vestibulosympathetic reflexes

    NASA Technical Reports Server (NTRS)

    Kerman, I. A.; Yates, B. J.; McAllen, R. M.

    2000-01-01

    To investigate the possibility that expression of vestibulosympathetic reflexes (VSR) is related to a nerve's anatomic location rather than its target organ, we compared VSR recorded from the same type of postganglionic fiber [muscle vasoconstrictor (MVC)] located at three different rostrocaudal levels: hindlimb, forelimb, and face. Experiments were performed on chloralose-anesthetized cats, and vestibular afferents were stimulated electrically. Single MVC unit activity was extracted by spike shape analysis of few-fiber recordings, and unit discrimination was confirmed by autocorrelation. Poststimulus time histogram analysis revealed that about half of the neurons were initially inhibited by vestibular stimulation (type 1 response), whereas the other MVC fibers were initially strongly excited (type 2 response). MVC units with types 1 and 2 responses were present in the same nerve fascicle. Barosensitivity was equivalent in the two groups, but fibers showing type 1 responses fired significantly faster than those giving type 2 responses (0.29 +/- 0.04 vs. 0.20 +/- 0.02 Hz). Nerve fibers with type 1 responses were most common in the hindlimb (21 of 29 units) and least common in the face (2 of 11 units), the difference in relative proportion being significant (P < 0.05, chi(2) test). These results support the hypothesis that VSR are anatomically patterned.

  15. Leveraging global gene expression patterns to predict expression of unmeasured genes.

    PubMed

    Rudd, James; Zelaya, René A; Demidenko, Eugene; Goode, Ellen L; Greene, Casey S; Doherty, Jennifer A

    2015-12-15

    Large collections of paraffin-embedded tissue represent a rich resource to test hypotheses based on gene expression patterns; however, measurement of genome-wide expression is cost-prohibitive on a large scale. Using the known expression correlation structure within a given disease type (in this case, high grade serous ovarian cancer; HGSC), we sought to identify reduced sets of directly measured (DM) genes which could accurately predict the expression of a maximized number of unmeasured genes. We developed a greedy gene set selection (GGS) algorithm which returns a DM set of user specified size based on a specific correlation threshold (|rP|) and minimum number of DM genes that must be correlated to an unmeasured gene in order to infer the value of the unmeasured gene (redundancy). We evaluated GGS in the Cancer Genome Atlas (TCGA) HGSC data across 144 combinations of DM size, redundancy (1-3), and |rP| (0.60, 0.65, 0.70). Across the parameter sweep, GGS allows on average 9 times more gene expression information to be captured compared to the DM set alone. GGS successfully augments prognostic HGSC gene sets; the addition of 20 GGS selected genes more than doubles the number of genes whose expression is predictable. Moreover, the expression prediction is highly accurate. After training regression models for the predictable gene set using 2/3 of the TCGA data, the average accuracy (ranked correlation of true and predicted values) in the 1/3 testing partition and four independent populations is above 0.65 and approaches 0.8 for conservative parameter sets. We observe similar accuracies in the TCGA HGSC RNA-sequencing data. Specifically, the prediction accuracy increases with increasing redundancy and increasing |rP|. GGS-selected genes, which maximize expression information about unmeasured genes, can be combined with candidate gene sets as a cost effective way to increase the amount of gene expression information obtained in large studies. This method can be applied

  16. Mining differential top-k co-expression patterns from time course comparative gene expression datasets

    PubMed Central

    2013-01-01

    Background Frequent pattern mining analysis applied on microarray dataset appears to be a promising strategy for identifying relationships between gene expression levels. Unfortunately, too many itemsets (co-expressed genes) are identified by this analysis method since it does not consider the importance of each gene within biological processes to a cellular response and does not take into account temporal properties under biological treatment-control matched conditions in a microarray dataset. Results We propose a method termed TIIM (Top-k Impactful Itemsets Miner), which only requires specifying a user-defined number k to explore the top k itemsets with the most significantly differentially co-expressed genes between 2 conditions in a time course. To give genes different weights, a table with impact degrees for each gene was constructed based on the number of neighboring genes that are differently expressed in the dataset within gene regulatory networks. Finally, the resulting top-k impactful itemsets were manually evaluated using previous literature and analyzed by a Gene Ontology enrichment method. Conclusions In this study, the proposed method was evaluated in 2 publicly available time course microarray datasets with 2 different experimental conditions. Both datasets identified potential itemsets with co-expressed genes evaluated from the literature and showed higher accuracies compared to the 2 corresponding control methods: i) performing TIIM without considering the gene expression differentiation between 2 different experimental conditions and impact degrees, and ii) performing TIIM with a constant impact degree for each gene. Our proposed method found that several new gene regulations involved in these itemsets were useful for biologists and provided further insights into the mechanisms underpinning biological processes. The Java source code and other related materials used in this study are available at

  17. The E4 protein; structure, function and patterns of expression.

    PubMed

    Doorbar, John

    2013-10-01

    the E1^E4 proteins main functions, the association with the cellular keratin network, and eventually also its cleavage by the protease calpain which allows assembly into amyloid-like fibres and reorganisation of the keratin network. Although the E4 proteins of different HPV types appear divergent at the level of their primary amino acid sequence, they share a recognisable modular organisation and pattern of expression, which may underlie conserved functions and regulation. Assembly into higher-order multimers and suppression of cell proliferation are common to all E4 proteins examined. Although not yet formally demonstrated, a role in virus release and transmission remains a likely function for E4.

  18. Analysis of spatial-temporal gene expression patterns reveals dynamics and regionalization in developing mouse brain.

    PubMed

    Chou, Shen-Ju; Wang, Chindi; Sintupisut, Nardnisa; Niou, Zhen-Xian; Lin, Chih-Hsu; Li, Ker-Chau; Yeang, Chen-Hsiang

    2016-01-20

    Allen Brain Atlas (ABA) provides a valuable resource of spatial/temporal gene expressions in mammalian brains. Despite rich information extracted from this database, current analyses suffer from several limitations. First, most studies are either gene-centric or region-centric, thus are inadequate to capture the superposition of multiple spatial-temporal patterns. Second, standard tools of expression analysis such as matrix factorization can capture those patterns but do not explicitly incorporate spatial dependency. To overcome those limitations, we proposed a computational method to detect recurrent patterns in the spatial-temporal gene expression data of developing mouse brains. We demonstrated that regional distinction in brain development could be revealed by localized gene expression patterns. The patterns expressed in the forebrain, medullary and pontomedullary, and basal ganglia are enriched with genes involved in forebrain development, locomotory behavior, and dopamine metabolism respectively. In addition, the timing of global gene expression patterns reflects the general trends of molecular events in mouse brain development. Furthermore, we validated functional implications of the inferred patterns by showing genes sharing similar spatial-temporal expression patterns with Lhx2 exhibited differential expression in the embryonic forebrains of Lhx2 mutant mice. These analysis outcomes confirm the utility of recurrent expression patterns in studying brain development.

  19. The expression patterns of three class B genes in two distinctive whorls of petaloid tepals in Alstroemeria ligtu.

    PubMed

    Hirai, Masayo; Kamimura, Taichi; Kanno, Akira

    2007-02-01

    Alstroemeria (Liliales) has two layers of petaloid tepals, in which the often spotted narrow inner tepals can be distinguished easily from the wider outer tepals. In order to explore this floral morphology in Alstroemeria, we investigated the tepal morphology and the expression patterns of three class B genes, whose homologs in eudicots have been shown previously to be involved in petal and stamen development. The two DEF-like genes (AlsDEFa and AlsDEFb) and the one GLO-like gene (AlsGLO) of Alstroemeria ligtu were isolated by rapid amplification of cDNA ends (RACE). Northern hybridization, reverse transcription-PCR (RT-PCR) and in situ hybridization analyses indicated that AlsDEFb and AlsGLO were expressed in whorls 1, 2 and 3 (outer tepals, inner tepals and stamens, respectively), whereas AlsDEFa expression was detected only in whorls 2 and 3. These results suggest that in A. ligtu, AlsDEFb and AlsGLO would participate in determining the organ identity of the two-layered petaloid tepals and stamens, which is in support of the modified ABC model. Additionally, the distinctive expression patterns of AlsDEFa and AlsDEFb might be related to morphological differences between the two-layered tepals.

  20. Distinguishing the effects of familiarity, relatedness, and color pattern rarity on attractiveness and measuring their effects on sexual selection in guppies (Poecilia reticulata).

    PubMed

    Zajitschek, Susanne R K; Brooks, Robert C

    2008-12-01

    Mate choice is often based on multiple signal traits and can be influenced by context-dependent factors. Understanding the importance of these signals and factors can be difficult because they are often correlated and might interact. Here, we experimentally disentangle the effects of familiarity, kinship, pattern rarity, and ornament patterns on mate choice in guppies. We estimate whether these factors alter sexual selection on six phenotypic traits known to influence male attractiveness. Rarity of the male's phenotype is the only context-dependent factor that significantly influenced female mating decisions, with common patterns being least attractive. This preference for rare male patterns is a source of negative frequency-dependent selection that may contribute to maintaining the extreme polymorphism in male guppy coloration. Neither visual familiarity nor relatedness between mating partners had any significant effect on mate choice decisions. There was significant linear and nonlinear sexual selection on ornamental traits, but this was not influenced by the context-dependent measures. Our approach highlights the complexity of female mate choice and sexual selection, as well as the value of combining multifactorial experiments with multivariate selection analyses. Our study shows that both negative frequency-dependent selection and disruptive selection contribute to the maintenance of extreme polymorphism in guppies.

  1. Impulse Control and Callous-Unemotional Traits Distinguish Patterns of Delinquency and Substance Use in Justice Involved Adolescents: Examining the Moderating Role of Neighborhood Context.

    PubMed

    Ray, James V; Thornton, Laura C; Frick, Paul J; Steinberg, Laurence; Cauffman, Elizabeth

    2016-04-01

    Both callous-unemotional (CU) traits and impulse control are known risk factors associated with delinquency and substance use. However, research is limited in how contextual factors such as neighborhood conditions influence the associations between these two dispositional factors and these two externalizing behaviors. The current study utilized latent class analysis (LCA) to identify unique classes of delinquency and substance use within an ethnically diverse sample (n = 1216) of justice-involved adolescents (ages 13 to 17) from three different sites. Neighborhood disorder, CU traits, and impulse control were all independently associated with membership in classes with more extensive histories of delinquency and substance use. The effects of CU traits and impulse control in distinguishing delinquent classes was invariant across levels of neighborhood disorder, whereas neighborhood disorder moderated the association between impulse control and substance use. Specifically, the probability of being in more severe substance using classes for those low in impulse control was stronger in neighborhoods with fewer indicators of social and physical disorder.

  2. Spatio-temporal expression patterns of anterior Hox genes during Nile tilapia (Oreochromis niloticus) embryonic development.

    PubMed

    Lyon, R Stewart; Davis, Adam; Scemama, Jean-Luc

    2013-01-01

    Hox genes encode transcription factors that function to pattern regional tissue identities along the anterior-posterior axis during animal embryonic development. Divergent nested Hox gene expression patterns within the posterior pharyngeal arches may play an important role in patterning morphological variation in the pharyngeal jaw apparatus (PJA) between evolutionarily divergent teleost fishes. Recent gene expression studies have shown the expression patterns from all Hox paralog group (PG) 2-6 genes in the posterior pharyngeal arches (PAs) for the Japanese medaka (Oryzias latipes) and from most genes of these PGs for the Nile tilapia (Oreochromis niloticus). While several orthologous Hox genes exhibit divergent spatial and temporal expression patterns between these two teleost species in the posterior PAs, several tilapia Hox gene expression patterns from PG3-6 must be documented for a full comparative study. Here we present the spatio-temporal expression patterns of hoxb3b, c3a, b4a, a5a, b5a, b5b, b6a and b6b in the neural tube and posterior PAs of the Nile tilapia. We show that several of these tilapia Hox genes exhibit divergent expression patterns in the posterior PAs from their medaka orthologs. We also compare these gene expression patterns to orthologs in other gnathostome vertebrates, including the dogfish shark.

  3. Digital Gene Expression Tag Profiling Analysis of the Gene Expression Patterns Regulating the Early Stage of Mouse Spermatogenesis

    PubMed Central

    Meng, Lijun; Liu, Meiling; Zhao, Lina; Hu, Fen; Ding, Cunbao; Wang, Yang; He, Baoling; Pan, Yuxin; Fang, Wei; Chen, Jing; Hu, Songnian; Jia, Mengchun

    2013-01-01

    Detailed characterization of the gene expression patterns in spermatogonia and primary spermatocytes is critical to understand the processes which occur prior to meiosis during normal spermatogenesis. The genome-wide expression profiles of mouse type B spermatogonia and primary spermatocytes were investigated using the Solexa/Illumina digital gene expression (DGE) system, a tag based high-throughput transcriptome sequencing method, and the developmental processes which occur during early spermatogenesis were systematically analyzed. Gene expression patterns vary significantly between mouse type B spermatogonia and primary spermatocytes. The functional analysis revealed that genes related to junction assembly, regulation of the actin cytoskeleton and pluripotency were most significantly differently expressed. Pathway analysis indicated that the Wnt non-canonical signaling pathway played a central role and interacted with the actin filament organization pathway during the development of spermatogonia. This study provides a foundation for further analysis of the gene expression patterns and signaling pathways which regulate the molecular mechanisms of early spermatogenesis. PMID:23554914

  4. A digital atlas of ion channel expression patterns in the two-week-old rat brain.

    PubMed

    Shcherbatyy, Volodymyr; Carson, James; Yaylaoglu, Murat; Jäckle, Katharina; Grabbe, Frauke; Brockmeyer, Maren; Yavuz, Halenur; Eichele, Gregor

    2015-01-01

    The approximately 350 ion channels encoded by the mammalian genome are a main pillar of the nervous system. We have determined the expression pattern of 320 channels in the two-week-old (P14) rat brain by means of non-radioactive robotic in situ hybridization. Optimized methods were developed and implemented to generate stringently coronal brain sections. The use of standardized methods permits a direct comparison of expression patterns across the entire ion channel expression pattern data set and facilitates recognizing ion channel co-expression. All expression data are made publically available at the Genepaint.org database. Inwardly rectifying potassium channels (Kir, encoded by the Kcnj genes) regulate a broad spectrum of physiological processes. Kcnj channel expression patterns generated in the present study were fitted with a deformable subdivision mesh atlas produced for the P14 rat brain. This co-registration, when combined with numerical quantification of expression strengths, allowed for semi-quantitative automated annotation of expression patterns as well as comparisons among and between Kcnj subfamilies. The expression patterns of Kcnj channel were also cross validated against previously published expression patterns of Kcnj channel genes.

  5. Analysis of molecular expression patterns and integration with other knowledge bases using probabilistic Bayesian network models

    SciTech Connect

    Moler, Edward J.; Mian, I.S.

    2000-03-01

    How can molecular expression experiments be interpreted with greater than ten to the fourth measurements per chip? How can one get the most quantitative information possible from the experimental data with good confidence? These are important questions whose solutions require an interdisciplinary combination of molecular and cellular biology, computer science, statistics, and complex systems analysis. The explosion of data from microarray techniques present the problem of interpreting the experiments. The availability of large-scale knowledge bases provide the opportunity to maximize the information extracted from these experiments. We have developed new methods of discovering biological function, metabolic pathways, and regulatory networks from these data and knowledge bases. These techniques are applicable to analyses for biomedical engineering, clinical, and fundamental cell and molecular biology studies. Our approach uses probabilistic, computational methods that give quantitative interpretations of data in a biological context. We have selected Bayesian statistical models with graphical network representations as a framework for our methods. As a first step, we use a nave Bayesian classifier to identify statistically significant patterns in gene expression data. We have developed methods which allow us to (a) characterize which genes or experiments distinguish each class from the others, (b) cross-index the resulting classes with other databases to assess biological meaning of the classes, and (c) display a gross overview of cellular dynamics. We have developed a number of visualization tools to convey the results. We report here our methods of classification and our first attempts at integrating the data and other knowledge bases together with new visualization tools. We demonstrate the utility of these methods and tools by analysis of a series of yeast cDNA microarray data and to a set of cancerous/normal sample data from colon cancer patients. We discuss

  6. Dynamic expression patterns of the new protocadherin families CNRs and Pcdh-gamma during mouse odontogenesis: comparison with reelin expression.

    PubMed

    Heymann, R; Kallenbach, S; Alonso, S; Carroll, P; Mitsiadis, T A

    2001-08-01

    Protocadherins are transmembrane glycoproteins belonging to the cadherin superfamily of molecules, which are involved in many biological processes such as cell adhesion, cytoskeletal organization and morphogenesis. Protocadherins generally exhibit only moderate adhesive activity and are highly expressed in the nervous system. Here, we report on the expression pattern of two novel families of protocadherins (CNRs and Pcdh-gamma) during rodent teeth development. Furthermore, we compare their expression with that of reelin, which is the potential ligand of CNRs. Throughout odontogenesis, CNRs, Pcdh-gamma and reelin show dynamic spatiotemporal expression patterns, which relate to both morphogenesis and cell differentiation events.

  7. Unique DNA methylation patterns distinguish non-invasive and invasive urothelial cancers and establish an epigenetic field defect in premalignant tissue

    PubMed Central

    Wolff, Erika M.; Chihara, Yoshitomo; Pan, Fei; Weisenberger, Daniel J.; Siegmund, Kimberly D.; Sugano, Kokichi; Kawashima, Kiyotaka; Laird, Peter W.; Jones, Peter A.; Liang, Gangning

    2010-01-01

    Urothelial cancer (UC) develops along two different genetic pathways, resulting in non-invasive or invasive tumors. However, it is unknown whether there are also different epigenetic pathways in UC. UC is also characterized by a high rate of recurrence and the presence of a field defect has been postulated. In this study, we compared the DNA methylation patterns between non-invasive and invasive UC, and the DNA methylation patterns in normal-appearing urothelium from bladders with cancer to urothelium from cancer-free bladders. We used the Illumina GoldenGate methylation assay at 1,370 loci in 49 non-invasive urothelial tumors, 38 invasive tumors with matched normal-appearing urothelium, and urothelium from 12 age-matched urothelial cancer-free patients. We found a distinct pattern of hypomethylation in the non-invasive tumors and widespread hypermethylation in the invasive tumors, confirming that the two pathways differ epigenetically in addition to genetically. We also found that 12% of the loci were hypermethylated in apparently normal urothelium from bladders with cancer, indicating an epigenetic field defect. X-chromosome inactivation analysis indicated that this field defect did not result in clonal expansion but occurred independently across the urothelium of bladders with cancer. The hypomethylation present in non-invasive tumors may counter-intuitively provide a biological explanation for the failure of these tumors to become invasive. In addition, an epithelium-wide epigenetic defect in bladders with cancer may contribute to a loss of epithelial integrity and create a permissible environment for tumors to arise. PMID:20841482

  8. Abnormal fatty acid pattern in the superior temporal gyrus distinguishes bipolar disorder from major depression and schizophrenia and resembles multiple sclerosis.

    PubMed

    McNamara, Robert K; Rider, Therese; Jandacek, Ronald; Tso, Patrick

    2014-03-30

    This study investigated the fatty acid composition of the postmortem superior temporal gyrus (STG), a cortical region implicated in emotional processing, from normal controls (n=15) and patients with bipolar disorder (BD, n=15), major depressive disorder (MDD, n=15), and schizophrenia (SZ, n=15). For comparative purposes, STG fatty acid composition was determined in a separate cohort of multiple sclerosis patients (MS, n=15) and normal controls (n=15). Compared with controls, patients with BD, but not MDD or SZ, exhibited abnormal elevations in the saturated fatty acids (SFA) palmitic acid (16:0), stearic acid (18:0), the polyunsaturated fatty acids (PUFA) linoleic acid (18:2n-6), arachidonic acid (20:4n-6), and docosahexaenoic acid (22:6n-3), and reductions in the monounsaturated fatty acid (MUFA) oleic acid (18:1n-9). The total MUFA/SFA and 18:1/18:0 ratios were lower in the STG of BD patients and were inversely correlated with total PUFA composition. MS patients exhibited a pattern of fatty acid abnormalities similar to that observed in BD patients including elevated PUFA and a lower 18:1/18:0 ratio. Collectively, these data demonstrate that BD patients exhibit a pattern of fatty acid abnormalities in the STG that is not observed in MDD and SZ patients and closely resembles MS patients.

  9. Expression pattern of protease activated receptors in lymphoid cells.

    PubMed

    López, Mercedes L; Soriano-Sarabia, Natalia; Bruges, Gustavo; Marquez, María Elena; Preissner, Klaus T; Schmitz, M Lienhard; Hackstein, Holger

    2014-01-01

    Protease-activated receptors (PARs) are a subfamily of four G-protein-coupled receptors mediating multiple functions. PARs expression was studied in subpopulations of human lymphocytes. Our results indicate that natural killer cells expressed mRNA for PAR₁, PAR₂ and PAR₃, CD4+ T cells expressed PAR₁ and PAR₂, while γδ and CD8+ T cells only expressed PAR₁. PAR₄ was absent at mRNA level and B cells did not express any PAR. Analyses of the cell surface PARs expression by flow cytometry were consistent with the mRNA data and also between different donors. PAR₁ is the most abundant member of the PAR family present in lymphocytes. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. A stable pattern of EEG spectral coherence distinguishes children with autism from neuro-typical controls - a large case control study

    PubMed Central

    2012-01-01

    Background The autism rate has recently increased to 1 in 100 children. Genetic studies demonstrate poorly understood complexity. Environmental factors apparently also play a role. Magnetic resonance imaging (MRI) studies demonstrate increased brain sizes and altered connectivity. Electroencephalogram (EEG) coherence studies confirm connectivity changes. However, genetic-, MRI- and/or EEG-based diagnostic tests are not yet available. The varied study results likely reflect methodological and population differences, small samples and, for EEG, lack of attention to group-specific artifact. Methods Of the 1,304 subjects who participated in this study, with ages ranging from 1 to 18 years old and assessed with comparable EEG studies, 463 children were diagnosed with autism spectrum disorder (ASD); 571 children were neuro-typical controls (C). After artifact management, principal components analysis (PCA) identified EEG spectral coherence factors with corresponding loading patterns. The 2- to 12-year-old subsample consisted of 430 ASD- and 554 C-group subjects (n = 984). Discriminant function analysis (DFA) determined the spectral coherence factors' discrimination success for the two groups. Loading patterns on the DFA-selected coherence factors described ASD-specific coherence differences when compared to controls. Results Total sample PCA of coherence data identified 40 factors which explained 50.8% of the total population variance. For the 2- to 12-year-olds, the 40 factors showed highly significant group differences (P < 0.0001). Ten randomly generated split half replications demonstrated high-average classification success (C, 88.5%; ASD, 86.0%). Still higher success was obtained in the more restricted age sub-samples using the jackknifing technique: 2- to 4-year-olds (C, 90.6%; ASD, 98.1%); 4- to 6-year-olds (C, 90.9%; ASD 99.1%); and 6- to 12-year-olds (C, 98.7%; ASD, 93.9%). Coherence loadings demonstrated reduced short-distance and reduced, as well as increased

  11. Visual Fixation Patterns during Reciprocal Social Interaction Distinguish a Subgroup of 6-Month-Old Infants At-Risk for Autism from Comparison Infants.

    PubMed

    Merin, Noah; Young, Gregory S; Ozonoff, Sally; Rogers, Sally J

    2007-01-01

    Thirty-one infant siblings of children with autism and 24 comparison infants were tested at 6 months of age during social interaction with a caregiver, using a modified Still Face paradigm conducted via a closed-circuit TV-video system. In the Still Face paradigm, the mother interacts with the infant, then freezes and displays a neutral, expressionless face, then resumes interaction. Eye tracking data on infant visual fixation patterns were recorded during the three episodes of the experiment. Using a hierarchical cluster analysis, we identified a subgroup of infants demonstrating diminished gaze to the mother's eyes relative to her mouth during the Still Face episode. Ten out of the 11 infants in this subgroup had an older sibling with autism.

  12. Automated annotation of Drosophila gene expression patterns using a controlled vocabulary.

    PubMed

    Ji, Shuiwang; Sun, Liang; Jin, Rong; Kumar, Sudhir; Ye, Jieping

    2008-09-01

    Regulation of gene expression in space and time directs its localization to a specific subset of cells during development. Systematic determination of the spatiotemporal dynamics of gene expression plays an important role in understanding the regulatory networks driving development. An atlas for the gene expression patterns of fruit fly Drosophila melanogaster has been created by whole-mount in situ hybridization, and it documents the dynamic changes of gene expression pattern during Drosophila embryogenesis. The spatial and temporal patterns of gene expression are integrated by anatomical terms from a controlled vocabulary linking together intermediate tissues developed from one another. Currently, the terms are assigned to patterns manually. However, the number of patterns generated by high-throughput in situ hybridization is rapidly increasing. It is, therefore, tempting to approach this problem by employing computational methods. In this article, we present a novel computational framework for annotating gene expression patterns using a controlled vocabulary. In the currently available high-throughput data, annotation terms are assigned to groups of patterns rather than to individual images. We propose to extract invariant features from images, and construct pyramid match kernels to measure the similarity between sets of patterns. To exploit the complementary information conveyed by different features and incorporate the correlation among patterns sharing common structures, we propose efficient convex formulations to integrate the kernels derived from various features. The proposed framework is evaluated by comparing its annotation with that of human curators, and promising performance in terms of F1 score has been reported.

  13. Differential expression of immune-related genes between healthy volunteers and type 2 diabetic patients with spleen-deficiency pattern.

    PubMed

    Chen, Longhui; Yang, Zemin; Chen, Weiwen; Li, Ruliu; Lin, Chuanquan; Guan, Lihua; Zhu, Zhangzhi; Chen, Ruifang; Li, Saimei; Zhao, Lingbo; Zeng, Jinhao; Wang, Jianhua

    2015-12-01

    To investigate the clinical differentia tion of spleen-deficiency pattern (SDP), a group of symptoms and signs defined in terms of Traditional Chinese Medicine for its clinical practice. Peripheral venous blood (> 3 mL) was collected from each of six type 2 diabetes mellitus (T2DM)-SDP patients and six healthy volunteers. After the isolation of peripheral white blood cells (PWBCs), total RNA was extracted, and quality control was performed on all RNA samples. Microarray experiments were conducted using the Agilent human whole genome gene chip, and genes demonstrating differential expression were screened. Bioinformatics analysis was conducted on these genes using several online databases. We screened a total of 175 differentially expressed genes (DEGs), of which 111 (63%) were down-regulated and 64 (37%) were up-regulated in T2DM-SDP patients compared with healthy controls. Among the 175 genes, 158 had biological function annotations: 46 (29%) were directly related to an individual's immune regulation or response, 25 (16%) were associated with substance and energy metabolism of PWBCs which could also indirectly influence immunity, and the remaining 87 (55%) were involved in a variety of PWBC biological processes that might eventually influence the immune function. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the DEGs were predominantly enriched in seven immune-related pathways. Hierarchical cluster analysis identified gene expression patterns that were distinguishable between the two study groups. Our results suggest that T2DM-SDP patients experience significant hypoimmunity and/or immune dysfunctions, and possess a specific gene expression profile. These findings offer new insights into SDP and the clinical pattern differentiation of T2DM-SDP.

  14. Patterns of gene expression in peripheral blood mononuclear cells and outcomes from patients with sepsis secondary to community acquired pneumonia.

    PubMed

    Severino, Patricia; Silva, Eliézer; Baggio-Zappia, Giovana Lotici; Brunialti, Milena Karina Coló; Nucci, Laura Alejandra; Rigato, Otelo; da Silva, Ismael Dale Cotrim Guerreiro; Machado, Flávia Ribeiro; Salomao, Reinaldo

    2014-01-01

    Mechanisms governing the inflammatory response during sepsis have been shown to be complex, involving cross-talk between diverse signaling pathways. Current knowledge regarding the mechanisms underlying sepsis provides an incomplete picture of the syndrome, justifying additional efforts to understand this condition. Microarray-based expression profiling is a powerful approach for the investigation of complex clinical conditions such as sepsis. In this study, we investigate whole-genome expression profiles in mononuclear cells from survivors (n = 5) and non-survivors (n = 5) of sepsis. To circumvent the heterogeneity of septic patients, only patients admitted with sepsis caused by community-acquired pneumonia were included. Blood samples were collected at the time of sepsis diagnosis and seven days later to evaluate the role of biological processes or genes possibly involved in patient recovery. Principal Components Analysis (PCA) profiling discriminated between patients with early sepsis and healthy individuals. Genes with differential expression were grouped according to Gene Ontology, and most genes related to immune defense were up-regulated in septic patients. Additionally, PCA in the early stage was able to distinguish survivors from non-survivors. Differences in oxidative phosphorylation seem to be associated with clinical outcome because significant differences in the expression profile of genes related to mitochondrial electron transport chain (ETC) I-V were observed between survivors and non-survivors at the time of patient enrollment. Global gene expression profiles after seven days of sepsis progression seem to reproduce, to a certain extent, patterns collected at the time of diagnosis. Gene expression profiles comparing admission and follow-up samples differed between survivors and non-survivors, with decreased expression of genes related to immune functions in non-survivors. In conclusion, genes related to host defense and inflammatory response

  15. Gender and Age Patterns in Emotional Expression, Body Image, and Self-Esteem: A Qualitative Analysis.

    ERIC Educational Resources Information Center

    Polce-Lynch, Mary; Myers, Barbara J.; Kilmartin, Christopher T.; Forssmann-Falck, Renate; Kliewer, Wendy

    1998-01-01

    Used written narratives to examine gender and age patterns in body image, emotional expression, and self-esteem for 209 students in grades 5, 8, and 12. Results indicate that boys restrict emotional expression in adolescence, whereas girls increase emotional expression in the same period. Girls also are more influenced by body image. (SLD)

  16. Gender and Age Patterns in Emotional Expression, Body Image, and Self-Esteem: A Qualitative Analysis.

    ERIC Educational Resources Information Center

    Polce-Lynch, Mary; Myers, Barbara J.; Kilmartin, Christopher T.; Forssmann-Falck, Renate; Kliewer, Wendy

    1998-01-01

    Used written narratives to examine gender and age patterns in body image, emotional expression, and self-esteem for 209 students in grades 5, 8, and 12. Results indicate that boys restrict emotional expression in adolescence, whereas girls increase emotional expression in the same period. Girls also are more influenced by body image. (SLD)

  17. Network Security via Biometric Recognition of Patterns of Gene Expression

    NASA Technical Reports Server (NTRS)

    Shaw, Harry C.

    2016-01-01

    Molecular biology provides the ability to implement forms of information and network security completely outside the bounds of legacy security protocols and algorithms. This paper addresses an approach which instantiates the power of gene expression for security. Molecular biology provides a rich source of gene expression and regulation mechanisms, which can be adopted to use in the information and electronic communication domains. Conventional security protocols are becoming increasingly vulnerable due to more intensive, highly capable attacks on the underlying mathematics of cryptography. Security protocols are being undermined by social engineering and substandard implementations by IT organizations. Molecular biology can provide countermeasures to these weak points with the current security approaches. Future advances in instruments for analyzing assays will also enable this protocol to advance from one of cryptographic algorithms to an integrated system of cryptographic algorithms and real-time expression and assay of gene expression products.

  18. The CD27+ memory B cells display changes in the gene expression pattern in elderly individuals

    PubMed Central

    Báez, Alicia; Álvarez-Laderas, Isabel; Piruat, José I; Caballero-Velázquez, Teresa; Barbado, María Victoria; Millán-Uclés, África; Medrano, Mayte; García-Guerrero, Estefanía; Sánchez-Abarca, Luis Ignacio; Pérez-Simón, José Antonio

    2015-01-01

    Memory B cells (MBCs) have a long lifespan compared with naive B cells (NBCs), remaining viable for years. This could predispose them to suffer misbalances in the gene expression pattern in the long term, which might be involved in the development of age-related B-cell disorders. In order to identify genes whose expression might change during life, we analysed the gene expression patterns of CD27− NBCs versus CD27+ MBCs in young and old subjects. Using microarray assays we observed that the expression pattern of CD27− NBCs versus CD27+ MBCs is significantly different. Furthermore, to evaluate the age effect, we compared the gene expression pattern of young versus aged subjects in both cell populations. Interestingly, we did not find significant differences in the CD27− NBC population between young and aged individuals, whereas we found 925 genes differentially expressed in CD27+ MBCs. Among these genes, 193 were also differentially expressed in CD27+ MBCs compared with CD27− NBCs, most of them involved in cell survival, cell growth and proliferation, cellular development and gene expression. We conclude that gene expression profiles of CD27− NBCs and CD27+ MBCs are different. Moreover, whereas the gene expression pattern of CD27+ MBCs varies with age, the same does not happen in CD27− NBCs. This suggests that MBCs undergo time-dependent changes, which could underlie a higher susceptibility to dysfunction with age. PMID:25196729

  19. PhyloPattern: regular expressions to identify complex patterns in phylogenetic trees

    PubMed Central

    Gouret, Philippe; Thompson, Julie D; Pontarotti, Pierre

    2009-01-01

    Background To effectively apply evolutionary concepts in genome-scale studies, large numbers of phylogenetic trees have to be automatically analysed, at a level approaching human expertise. Complex architectures must be recognized within the trees, so that associated information can be extracted. Results Here, we present a new software library, PhyloPattern, for automating tree manipulations and analysis. PhyloPattern includes three main modules, which address essential tasks in high-throughput phylogenetic tree analysis: node annotation, pattern matching, and tree comparison. PhyloPattern thus allows the programmer to focus on: i) the use of predefined or user defined annotation functions to perform immediate or deferred evaluation of node properties, ii) the search for user-defined patterns in large phylogenetic trees, iii) the pairwise comparison of trees by dynamically generating patterns from one tree and applying them to the other. Conclusion PhyloPattern greatly simplifies and accelerates the work of the computer scientist in the evolutionary biology field. The library has been used to automatically identify phylogenetic evidence for domain shuffling or gene loss events in the evolutionary histories of protein sequences. However any workflow that relies on phylogenetic tree analysis, could be automated with PhyloPattern. PMID:19765311

  20. Human speech- and reading-related genes display partially overlapping expression patterns in the marmoset brain.

    PubMed

    Kato, Masaki; Okanoya, Kazuo; Koike, Taku; Sasaki, Erika; Okano, Hideyuki; Watanabe, Shigeru; Iriki, Atsushi

    2014-06-01

    Language is a characteristic feature of human communication. Several familial language impairments have been identified, and candidate genes for language impairments already isolated. Studies comparing expression patterns of these genes in human brain are necessary to further understanding of these genes. However, it is difficult to examine gene expression in human brain. In this study, we used a non-human primate (common marmoset; Callithrix jacchus) as a biological model of the human brain to investigate expression patterns of human speech- and reading-related genes. Expression patterns of speech disorder- (FoxP2, FoxP1, CNTNAP2, and CMIP) and dyslexia- (ROBO1, DCDC2, and KIAA0319) related genes were analyzed. We found the genes displayed overlapping expression patterns in the ocular, auditory, and motor systems. Our results enhance understanding of the molecular mechanisms underlying language impairments.

  1. 3D expression patterns of cell cycle genes in the developing chick wing and comparison with expression patterns of genes implicated in digit specification.

    PubMed

    Welten, Monique; Pavlovska, Gordana; Chen, Yu; Teruoka, Yuko; Fisher, Malcolm; Bangs, Fiona; Towers, Matthew; Tickle, Cheryll

    2011-05-01

    Sonic hedgehog (Shh) signalling controls integrated specification of digit pattern and growth in the chick wing but downstream gene networks remain to be unravelled. We analysed 3D expression patterns of genes encoding cell cycle regulators using Optical Projection Tomography. Hierarchical clustering of spatial matrices of gene expression revealed a dorsal layer of the wing bud, in which almost all genes were expressed, and that genes encoding positive cell cycle regulators had similar expression patterns while those of N-myc and CyclinD2 were distinct but closely related. We compared these patterns computationally with those of genes implicated in digit specification and Ptch1, 50 genes in total. Nineteen genes have similar posterior expression to Ptch1, including Hoxd13, Sall1, Hoxd11, and Bmp2, all likely Gli targets in mouse limb, and cell cycle genes, N-myc, CyclinD2. We suggest that these genes contribute to a network integrating digit specification and growth in response to Shh.

  2. Mitochondrial DNA haplotypes induce differential patterns of DNA methylation that result in differential chromosomal gene expression patterns

    PubMed Central

    Lee, William T; Sun, Xin; Tsai, Te-Sha; Johnson, Jacqueline L; Gould, Jodee A; Garama, Daniel J; Gough, Daniel J; McKenzie, Matthew; Trounce, Ian A; St. John, Justin C

    2017-01-01

    Mitochondrial DNA copy number is strictly regulated during development as naive cells differentiate into mature cells to ensure that specific cell types have sufficient copies of mitochondrial DNA to perform their specialised functions. Mitochondrial DNA haplotypes are defined as specific regions of mitochondrial DNA that cluster with other mitochondrial sequences to show the phylogenetic origins of maternal lineages. Mitochondrial DNA haplotypes are associated with a range of phenotypes and disease. To understand how mitochondrial DNA haplotypes induce these characteristics, we used four embryonic stem cell lines that have the same set of chromosomes but possess different mitochondrial DNA haplotypes. We show that mitochondrial DNA haplotypes influence changes in chromosomal gene expression and affinity for nuclear-encoded mitochondrial DNA replication factors to modulate mitochondrial DNA copy number, two events that act synchronously during differentiation. Global DNA methylation analysis showed that each haplotype induces distinct DNA methylation patterns, which, when modulated by DNA demethylation agents, resulted in skewed gene expression patterns that highlight the effectiveness of the new DNA methylation patterns established by each haplotype. The haplotypes differentially regulate α-ketoglutarate, a metabolite from the TCA cycle that modulates the TET family of proteins, which catalyse the transition from 5-methylcytosine, indicative of DNA methylation, to 5-hydroxymethylcytosine, indicative of DNA demethylation. Our outcomes show that mitochondrial DNA haplotypes differentially modulate chromosomal gene expression patterns of naive and differentiating cells by establishing mitochondrial DNA haplotype-specific DNA methylation patterns. PMID:28900542

  3. [Phylogenetic analysis and expression patterns of tropomyosin in amphioxus].

    PubMed

    Li, Xin-Yi; Lin, Yu-Shuang; Zhang, Hong-Wei

    2012-08-01

    In amphioxus, we found a mesoderm related gene, tropomyosin, which encodes a protein comprising 284 amino acid residues, sharing high identities with other known Tropomyosin proteins both in vertebrates and invertebrates. Phylogenetically, amphioxus Tropomyosin fell outside the invertebrate clade and was at the base of the vertebrate protein family clade, indicating that it may represent an independent branch. From the early neurula to the larva stage, whole-mount in situ hybridization and histological sections found transcripts of amphioxus tropomyosin gene. Weak tropomyosin expression was first detected in the wall of the archenteron at about 10 hours-post-fertilization neurula stage, while intense expression was revealed in the differentiating presumptive notochord and the muscle. Transcripts of tropomyosin were then expressed in the formed notochord and somites. Gene expression seemed to continue in these developing organs throughout the neurular stages and remained till 72-hours, during the early larval stages. In situ study still showed tropomyosin was also expressed in the neural tube, hepatic diverticulum, notochord and the spaces between myotomes in adult amphioxus. Our results indicated that tropomyosin may play an important role in both embryonic development and adult life.

  4. Microspatial gene expression patterns in the Amazon River Plume.

    PubMed

    Satinsky, Brandon M; Crump, Byron C; Smith, Christa B; Sharma, Shalabh; Zielinski, Brian L; Doherty, Mary; Meng, Jun; Sun, Shulei; Medeiros, Patricia M; Paul, John H; Coles, Victoria J; Yager, Patricia L; Moran, Mary Ann

    2014-07-29

    We investigated expression of genes mediating elemental cycling at the microspatial scale in the ocean's largest river plume using, to our knowledge, the first fully quantitative inventory of genes and transcripts. The bacterial and archaeal communities associated with a phytoplankton bloom in Amazon River Plume waters at the outer continental shelf in June 2010 harbored ∼ 1.0 × 10(13) genes and 4.7 × 10(11) transcripts per liter that mapped to several thousand microbial genomes. Genomes from free-living cells were more abundant than those from particle-associated cells, and they generated more transcripts per liter for carbon fixation, heterotrophy, nitrogen and phosphorus uptake, and iron acquisition, although they had lower expression ratios (transcripts ⋅ gene(-1)) overall. Genomes from particle-associated cells contributed more transcripts for sulfur cycling, aromatic compound degradation, and the synthesis of biologically essential vitamins, with an overall twofold up-regulation of expression compared with free-living cells. Quantitatively, gene regulation differences were more important than genome abundance differences in explaining why microenvironment transcriptomes differed. Taxa contributing genomes to both free-living and particle-associated communities had up to 65% of their expressed genes regulated differently between the two, quantifying the extent of transcriptional plasticity in marine microbes in situ. In response to patchiness in carbon, nutrients, and light at the micrometer scale, Amazon Plume microbes regulated the expression of genes relevant to biogeochemical processes at the ecosystem scale.

  5. Microspatial gene expression patterns in the Amazon River Plume

    PubMed Central

    Satinsky, Brandon M.; Crump, Byron C.; Smith, Christa B.; Sharma, Shalabh; Zielinski, Brian L.; Doherty, Mary; Meng, Jun; Sun, Shulei; Medeiros, Patricia M.; Paul, John H.; Coles, Victoria J.; Yager, Patricia L.; Moran, Mary Ann

    2014-01-01

    We investigated expression of genes mediating elemental cycling at the microspatial scale in the ocean’s largest river plume using, to our knowledge, the first fully quantitative inventory of genes and transcripts. The bacterial and archaeal communities associated with a phytoplankton bloom in Amazon River Plume waters at the outer continental shelf in June 2010 harbored ∼1.0 × 1013 genes and 4.7 × 1011 transcripts per liter that mapped to several thousand microbial genomes. Genomes from free-living cells were more abundant than those from particle-associated cells, and they generated more transcripts per liter for carbon fixation, heterotrophy, nitrogen and phosphorus uptake, and iron acquisition, although they had lower expression ratios (transcripts⋅gene−1) overall. Genomes from particle-associated cells contributed more transcripts for sulfur cycling, aromatic compound degradation, and the synthesis of biologically essential vitamins, with an overall twofold up-regulation of expression compared with free-living cells. Quantitatively, gene regulation differences were more important than genome abundance differences in explaining why microenvironment transcriptomes differed. Taxa contributing genomes to both free-living and particle-associated communities had up to 65% of their expressed genes regulated differently between the two, quantifying the extent of transcriptional plasticity in marine microbes in situ. In response to patchiness in carbon, nutrients, and light at the micrometer scale, Amazon Plume microbes regulated the expression of genes relevant to biogeochemical processes at the ecosystem scale. PMID:25024226

  6. The legacy of diploid progenitors in allopolyploid gene expression patterns

    PubMed Central

    Buggs, Richard J. A.; Wendel, Jonathan F.; Doyle, Jeffrey J.; Soltis, Douglas E.; Soltis, Pamela S.; Coate, Jeremy E.

    2014-01-01

    Allopolyploidization (hybridization and whole-genome duplication) is a common phenomenon in plant evolution with immediate saltational effects on genome structure and gene expression. New technologies have allowed rapid progress over the past decade in our understanding of the consequences of allopolyploidy. A major question, raised by early pioneer of this field Leslie Gottlieb, concerned the extent to which gene expression differences among duplicate genes present in an allopolyploid are a legacy of expression differences that were already present in the progenitor diploid species. Addressing this question necessitates phylogenetically well-understood natural study systems, appropriate technology, availability of genomic resources and a suitable analytical framework, including a sufficiently detailed and generally accepted terminology. Here, we review these requirements and illustrate their application to a natural study system that Gottlieb worked on and recommended for this purpose: recent allopolyploids of Tragopogon (Asteraceae). We reanalyse recent data from this system within the conceptual framework of parental legacies on duplicate gene expression in allopolyploids. On a broader level, we highlight the intellectual connection between Gottlieb's phrasing of this issue and the more contemporary framework of cis- versus trans-regulation of duplicate gene expression in allopolyploid plants. PMID:24958927

  7. Network Security via Biometric Recognition of Patterns of Gene Expression

    NASA Technical Reports Server (NTRS)

    Shaw, Harry C.

    2016-01-01

    Molecular biology provides the ability to implement forms of information and network security completely outside the bounds of legacy security protocols and algorithms. This paper addresses an approach which instantiates the power of gene expression for security. Molecular biology provides a rich source of gene expression and regulation mechanisms, which can be adopted to use in the information and electronic communication domains. Conventional security protocols are becoming increasingly vulnerable due to more intensive, highly capable attacks on the underlying mathematics of cryptography. Security protocols are being undermined by social engineering and substandard implementations by IT (Information Technology) organizations. Molecular biology can provide countermeasures to these weak points with the current security approaches. Future advances in instruments for analyzing assays will also enable this protocol to advance from one of cryptographic algorithms to an integrated system of cryptographic algorithms and real-time assays of gene expression products.

  8. Microarray analysis of circular RNA expression patterns in polarized macrophages

    PubMed Central

    Zhang, Yingying; Zhang, Yao; Li, Xueqin; Zhang, Mengying; Lv, Kun

    2017-01-01

    Circular RNAs (circRNAs) are generated from diverse genomic locations and are a new player in the regulation of post-transcriptional gene expression. Recent studies have revealed that circRNAs play a crucial role in fine-tuning the level of microRNA (miRNA)-mediated regulation of gene expression by sequestering miRNAs. The interaction of circRNAs with disease-associated miRNAs suggests that circRNAs are important in the pathology of disease. However, the effects and roles of circRNAs in macrophage polarization have yet to be explored. In the present study, we performed a circRNA microarray to compare the circRNA expression profiles of bone marrow-derived macrophages (BMDMs) under two distinct polarizing conditions (M1 macrophages induced by interferon-γ and LPS stimulation, and M2 macrophages induced by interleukin-4 stimulation). Our results showed that a total of 189 circRNAs were differentially expressed between M1 and M2 macrophages. Differentially expressed circRNAs with a high fold-change were selected for validation by RT-qPCR: circRNA-003780, circRNA-010056, and circRNA-010231 were upregulated and circRNA-003424, circRNA-013630, circRNA-001489 and circRNA-018127 were downregulated (fold-change >4, P<0.05) in M1 compared to M2, which was found to correlate with the microarray data. Furthermore, the most differentially expressed circRNAs within all the comparisons were annotated in detail with circRNA/miRNA interaction information using miRNA target prediction software. In conclusion, the present study provides novel insight into the role of circRNAs in macrophage differentiation and polarization. PMID:28075448

  9. Visualization and analysis of 3D gene expression patterns in zebrafish using web services

    NASA Astrophysics Data System (ADS)

    Potikanond, D.; Verbeek, F. J.

    2012-01-01

    The analysis of patterns of gene expression patterns analysis plays an important role in developmental biology and molecular genetics. Visualizing both quantitative and spatio-temporal aspects of gene expression patterns together with referenced anatomical structures of a model-organism in 3D can help identifying how a group of genes are expressed at a certain location at a particular developmental stage of an organism. In this paper, we present an approach to provide an online visualization of gene expression data in zebrafish (Danio rerio) within 3D reconstruction model of zebrafish in different developmental stages. We developed web services that provide programmable access to the 3D reconstruction data and spatial-temporal gene expression data maintained in our local repositories. To demonstrate this work, we develop a web application that uses these web services to retrieve data from our local information systems. The web application also retrieve relevant analysis of microarray gene expression data from an external community resource; i.e. the ArrayExpress Atlas. All the relevant gene expression patterns data are subsequently integrated with the reconstruction data of the zebrafish atlas using ontology based mapping. The resulting visualization provides quantitative and spatial information on patterns of gene expression in a 3D graphical representation of the zebrafish atlas in a certain developmental stage. To deliver the visualization to the user, we developed a Java based 3D viewer client that can be integrated in a web interface allowing the user to visualize the integrated information over the Internet.

  10. Hox expression in the American alligator and evolution of archosaurian axial patterning.

    PubMed

    Mansfield, Jennifer H; Abzhanov, Arhat

    2010-12-15

    The avian body plan has undergone many modifications, most associated with adaptation to flight and bipedal walking. Some of these modifications may be owing to avian-specific changes in the embryonic Hox expression code. Here, we have examined Hox expression in alligator, the closest living relative of birds, and an archosaur with a more conservative body plan. Two differences in Hox expression between chick, alligator, and other tetrapods correlate with aspects of alligator or bird-specific skeletal morphology. First, absence of a thoracic subdomain of Hoxc-8 expression in alligator correlates with morphological adaptations in crocodilian thoracic segments. Second, Hoxa-5, a gene required to pattern the cervical-thoracic transition, shows unique patterns of expression in chick, alligator, and mouse, correlating with species-specific morphological patterning of this region. Given that cervical vertebral morphologies evolved independently in the bird and mammalian lineages, the underlying developmental mechanisms, including refinement of Hox expression domains, may be distinct.

  11. The maize (Zea mays L.) AUXIN/INDOLE-3-ACETIC ACID gene family: phylogeny, synteny, and unique root-type and tissue-specific expression patterns during development.

    PubMed

    Ludwig, Yvonne; Zhang, Yanxiang; Hochholdinger, Frank

    2013-01-01

    The plant hormone auxin plays a key role in the coordination of many aspects of growth and development. AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) genes encode instable primary auxin responsive regulators of plant development that display a protein structure with four characteristic domains. In the present study, a comprehensive analysis of the 34 members of the maize Aux/IAA gene family was performed. Phylogenetic reconstructions revealed two classes of Aux/IAA proteins that can be distinguished by alterations in their domain III. Seven pairs of paralogous maize Aux/IAA proteins were discovered. Comprehensive root-type and tissue-specific expression profiling revealed unique expression patterns of the diverse members of the gene family. Remarkably, five of seven pairs of paralogous genes displayed highly correlated expression patterns in roots. All but one (ZmIAA23) tested maize Aux/IAA genes were auxin inducible, displaying two types of auxin induction within three hours of treatment. Moreover, 51 of 55 (93%) differential Aux/IAA expression patterns between different root-types followed the expression tendency: crown roots > seminal roots > primary roots > lateral roots. This pattern might imply root-type-specific regulation of Aux/IAA transcript abundance. In summary, the detailed analysis of the maize Aux/IAA gene family provides novel insights in the evolution and developmental regulation and thus the function of these genes in different root-types and tissues.

  12. Gene expression patterns associated with queen honey bee longevity.

    PubMed

    Corona, Miguel; Hughes, Kimberly A; Weaver, Daniel B; Robinson, Gene E

    2005-11-01

    The oxidative stress theory of aging proposes that accumulation of oxidative damage is the main proximate cause of aging and that lifespan is determined by the rate at which this damage occurs. Two predictions from this theory are that long-lived organisms produce fewer ROS or have increased antioxidant production. Based in these predictions, molecular mechanisms to promote longevity could include either changes in the regulation of mitochondrial genes that affect ROS production or elevated expression of antioxidant genes. We explored these possibilities in the honey bee, a good model for the study of aging because it has a caste system in which the same genome produces both a long-lived queen and a short-lived worker. We measured mRNA levels for genes encoding eight of the most prominent antioxidant enzymes and five mitochondrial proteins involved in respiration. The expression of antioxidant genes generally decreased with age in queens, but not in workers. Expression of most mitochondrial genes, in particular CytC, was higher in young queens, but these genes showed a faster age-related decline relative to workers. One exception to this trend was COX-I in thorax. This resulted in higher COX-I/CytC ratios in old queens compared to old workers, which suggests caste-specific differences in mitochondrial function that might be related to the caste-specific differences in longevity. Queen honey bee longevity appears to have evolved via mechanisms other than increased antioxidant gene expression.

  13. Muscle Gene Expression Patterns in Human Rotator Cuff Pathology

    PubMed Central

    Choo, Alexander; McCarthy, Meagan; Pichika, Rajeswari; Sato, Eugene J.; Lieber, Richard L.; Schenk, Simon; Lane, John G.; Ward, Samuel R.

    2014-01-01

    Background: Rotator cuff pathology is a common source of shoulder pain with variable etiology and pathoanatomical characteristics. Pathological processes of fatty infiltration, muscle atrophy, and fibrosis have all been invoked as causes for poor outcomes after rotator cuff tear repair. The aims of this study were to measure the expression of key genes associated with adipogenesis, myogenesis, and fibrosis in human rotator cuff muscle after injury and to compare the expression among groups of patients with varied severities of rotator cuff pathology. Methods: Biopsies of the supraspinatus muscle were obtained arthroscopically from twenty-seven patients in the following operative groups: bursitis (n = 10), tendinopathy (n = 7), full-thickness rotator cuff tear (n = 8), and massive rotator cuff tear (n = 2). Quantitative polymerase chain reaction (qPCR) was performed to characterize gene expression pathways involved in myogenesis, adipogenesis, and fibrosis. Results: Patients with a massive tear demonstrated downregulation of the fibrogenic, adipogenic, and myogenic genes, indicating that the muscle was not in a state of active change and may have difficulty responding to stimuli. Patients with a full-thickness tear showed upregulation of fibrotic and adipogenic genes; at the tissue level, these correspond to the pathologies most detrimental to outcomes of surgical repair. Patients with bursitis or tendinopathy still expressed myogenic genes, indicating that the muscle may be attempting to accommodate the mechanical deficiencies induced by the tendon tear. Conclusions: Gene expression in human rotator cuff muscles varied according to tendon injury severity. Patients with bursitis and tendinopathy appeared to be expressing pro-myogenic genes, whereas patients with a full-thickness tear were expressing genes associated with fatty atrophy and fibrosis. In contrast, patients with a massive tear appeared to have downregulation of all gene programs except inhibition of

  14. Muscle gene expression patterns in human rotator cuff pathology.

    PubMed

    Choo, Alexander; McCarthy, Meagan; Pichika, Rajeswari; Sato, Eugene J; Lieber, Richard L; Schenk, Simon; Lane, John G; Ward, Samuel R

    2014-09-17

    Rotator cuff pathology is a common source of shoulder pain with variable etiology and pathoanatomical characteristics. Pathological processes of fatty infiltration, muscle atrophy, and fibrosis have all been invoked as causes for poor outcomes after rotator cuff tear repair. The aims of this study were to measure the expression of key genes associated with adipogenesis, myogenesis, and fibrosis in human rotator cuff muscle after injury and to compare the expression among groups of patients with varied severities of rotator cuff pathology. Biopsies of the supraspinatus muscle were obtained arthroscopically from twenty-seven patients in the following operative groups: bursitis (n = 10), tendinopathy (n = 7), full-thickness rotator cuff tear (n = 8), and massive rotator cuff tear (n = 2). Quantitative polymerase chain reaction (qPCR) was performed to characterize gene expression pathways involved in myogenesis, adipogenesis, and fibrosis. Patients with a massive tear demonstrated downregulation of the fibrogenic, adipogenic, and myogenic genes, indicating that the muscle was not in a state of active change and may have difficulty responding to stimuli. Patients with a full-thickness tear showed upregulation of fibrotic and adipogenic genes; at the tissue level, these correspond to the pathologies most detrimental to outcomes of surgical repair. Patients with bursitis or tendinopathy still expressed myogenic genes, indicating that the muscle may be attempting to accommodate the mechanical deficiencies induced by the tendon tear. Gene expression in human rotator cuff muscles varied according to tendon injury severity. Patients with bursitis and tendinopathy appeared to be expressing pro-myogenic genes, whereas patients with a full-thickness tear were expressing genes associated with fatty atrophy and fibrosis. In contrast, patients with a massive tear appeared to have downregulation of all gene programs except inhibition of myogenesis. These data highlight the

  15. Binary Gene Expression Patterning of the Molt Cycle: The Case of Chitin Metabolism

    PubMed Central

    Abehsera, Shai; Glazer, Lilah; Tynyakov, Jenny; Plaschkes, Inbar; Chalifa-Caspi, Vered; Khalaila, Isam; Aflalo, Eliahu D.; Sagi, Amir

    2015-01-01

    In crustaceans, like all arthropods, growth is accompanied by a molting cycle. This cycle comprises major physiological events in which mineralized chitinous structures are built and degraded. These events are in turn governed by genes whose patterns of expression are presumably linked to the molting cycle. To study these genes we performed next generation sequencing and constructed a molt-related transcriptomic library from two exoskeletal-forming tissues of the crayfish Cherax quadricarinatus, namely the gastrolith and the mandible cuticle-forming epithelium. To simplify the study of such a complex process as molting, a novel approach, binary patterning of gene expression, was employed. This approach revealed that key genes involved in the synthesis and breakdown of chitin exhibit a molt-related pattern in the gastrolith-forming epithelium. On the other hand, the same genes in the mandible cuticle-forming epithelium showed a molt-independent pattern of expression. Genes related to the metabolism of glucosamine-6-phosphate, a chitin precursor synthesized from simple sugars, showed a molt-related pattern of expression in both tissues. The binary patterning approach unfolds typical patterns of gene expression during the molt cycle of a crustacean. The use of such a simplifying integrative tool for assessing gene patterning seems appropriate for the study of complex biological processes. PMID:25919476

  16. Macrophage polarization alters the expression and sulfation pattern of glycosaminoglycans.

    PubMed

    Martinez, Pierre; Denys, Agnès; Delos, Maxime; Sikora, Anne-Sophie; Carpentier, Mathieu; Julien, Sylvain; Pestel, Joël; Allain, Fabrice

    2015-05-01

    Macrophages are major cells of inflammatory process and take part in a large number of physiological and pathological processes. According to tissue environment, they can polarize into pro-inflammatory (M1) or alternative (M2) cells. Although many evidences have hinted to a potential role of cell-surface glycosaminoglycans (GAGs) in the functions of macrophages, the effect of M1 or M2 polarization on the biosynthesis of these polysaccharides has not been investigated so far. GAGs are composed of repeat sulfated disaccharide units. Heparan (HS) and chondroitin/dermatan sulfates (CS/DS) are the major GAGs expressed at the cell membrane. They are involved in numerous biological processes, which rely on their ability to selectively interact with a large panel of proteins. More than 20 genes encoding sulfotransferases have been implicated in HS and CS/DS biosynthesis, and the functional repertoire of HS and CS/DS has been related to the expression of these isoenzymes. In this study, we analyzed the expression of sulfotransferases as a response to macrophage polarization. We found that M1 and M2 activation drastically modified the profiles of expression of numerous HS and CS/DS sulfotransferases. This was accompanied by the expression of GAGs with distinct structural features. We then demonstrated that GAGs of M2 macrophages were efficient to present fibroblast growth factor-2 in an assay of tumor cell proliferation, thus indicating that changes in GAG structure may contribute to the functions of polarized macrophages. Altogether, our findings suggest a regulatory mechanism in which fine modifications in GAG biosynthesis may participate to the plasticity of macrophage functions. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. EMAGE: a spatial database of gene expression patterns during mouse embryo development

    PubMed Central

    Christiansen, Jeffrey H.; Yang, Yiya; Venkataraman, Shanmugasundaram; Richardson, Lorna; Stevenson, Peter; Burton, Nicholas; Baldock, Richard A.; Davidson, Duncan R.

    2006-01-01

    EMAGE () is a freely available, curated database of gene expression patterns generated by in situ techniques in the developing mouse embryo. It is unique in that it contains standardized spatial representations of the sites of gene expression for each gene, denoted against a set of virtual reference embryo models. As such, the data can be interrogated in a novel and abstract manner by using space to define a query. Accompanying the spatial representations of gene expression patterns are text descriptions of the sites of expression, which also allows searching of the data by more conventional text-based methods. PMID:16381949

  18. EMAGE: a spatial database of gene expression patterns during mouse embryo development.

    PubMed

    Christiansen, Jeffrey H; Yang, Yiya; Venkataraman, Shanmugasundaram; Richardson, Lorna; Stevenson, Peter; Burton, Nicholas; Baldock, Richard A; Davidson, Duncan R

    2006-01-01

    EMAGE (http://genex.hgu.mrc.ac.uk/Emage/database) is a freely available, curated database of gene expression patterns generated by in situ techniques in the developing mouse embryo. It is unique in that it contains standardized spatial representations of the sites of gene expression for each gene, denoted against a set of virtual reference embryo models. As such, the data can be interrogated in a novel and abstract manner by using space to define a query. Accompanying the spatial representations of gene expression patterns are text descriptions of the sites of expression, which also allows searching of the data by more conventional text-based methods.

  19. Comparative transcriptomics of three Poaceae species reveals patterns of gene expression evolution.

    PubMed

    Davidson, Rebecca M; Gowda, Malali; Moghe, Gaurav; Lin, Haining; Vaillancourt, Brieanne; Shiu, Shin-Han; Jiang, Ning; Robin Buell, C

    2012-08-01

    The Poaceae family, also known as the grasses, includes agronomically important cereal crops such as rice, maize, sorghum, and wheat. Previous comparative studies have shown that much of the gene content is shared among the grasses; however, functional conservation of orthologous genes has yet to be explored. To gain an understanding of the genome-wide patterns of evolution of gene expression across reproductive tissues, we employed a sequence-based approach to compare analogous transcriptomes in species representing three Poaceae subgroups including the Pooideae (Brachypodium distachyon), the Panicoideae (sorghum), and the Ehrhartoideae (rice). Our transcriptome analyses reveal that only a fraction of orthologous genes exhibit conserved expression patterns. A high proportion of conserved orthologs include genes that are upregulated in physiologically similar tissues such as leaves, anther, pistil, and embryo, while orthologs that are highly expressed in seeds show the most diverged expression patterns. More generally, we show that evolution of gene expression profiles and coding sequences in the grasses may be linked. Genes that are highly and broadly expressed tend to be conserved at the coding sequence level while genes with narrow expression patterns show accelerated rates of sequence evolution. We further show that orthologs in syntenic genomic blocks are more likely to share correlated expression patterns compared with non-syntenic orthologs. These findings are important for agricultural improvement because sequence information is transferred from model species, such as Brachypodium, rice, and sorghum to crop plants without sequenced genomes. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

  20. Spatiotemporal patterns of Musashi1 expression during inner ear development.

    PubMed

    Sakaguchi, Hirofumi; Yaoi, Takeshi; Suzuki, Toshihiro; Okano, Hideyuki; Hisa, Yasuo; Fushiki, Shinji

    2004-04-29

    Musashi1 (Msi 1) is an RNA binding protein associated with asymmetric cell divisions in neural progenitor cells. To investigate the involvement of Msi1 in the inner ear development, we studied the expression of Msi1 in mouse inner ears with RT-PCR and immunohistochemistry. Immunohistochemistry revealed that Msi1 was expressed in all otocyst cells at embryonic day (E) 10 and 12. Msi1 immunoreactivity became lost in hair cells after E14 in vestibule and after E16 in cochlea, whereas it persisted in supporting cells until adulthood. The subcellular localization of Msi1 changed from "cytoplasmic predominance" to "nuclear predominance" during the first 2 weeks after birth. The present data suggested that Msi may play a role in inner ear development.

  1. Spatiotemporal patterns of Gem expression after rat spinal cord injury.

    PubMed

    Wen, Hai; Cao, Jianhua; Yu, Xiaowei; Sun, Binbin; Ding, Tao; Li, Ming; Li, Debao; Wu, Hao; Long, Long; Xu, Guangfei; Zhang, Feng

    2013-06-21

    Gem is an atypical protein of the Ras superfamily that plays a role in regulating voltage-gated Ca(2+) channels and cytoskeletal reorganization. To elucidate the certain expression and biological function in central nervous system (CNS), we performed an acute spinal cord contusion injury model in adult rats. Western blot analysis showed a marked up-regulation of Gem after spinal cord injury (SCI). Immunohistochemistry revealed wide distribution of Gem in spinal cord, including neurons and glial cells. Double immunofluorescent staining for proliferating cell nuclear antigen (PCNA) and phenotype-specific markers indicated increases of Gem expression in proliferating microglia and astrocytes. Our data suggest that Gem may be implicated in the proliferation of microglia and astrocytes after SCI. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Temporal Patterns of Gene Expression During Calyx of Held Development

    PubMed Central

    Kolson, D. R.; Wan, J.; Wu, J.; Dehoff, M.; Brandebura, A. N.; Qian, J.; Mathers, P. H.; Spirou, G. A.

    2015-01-01

    Relating changes in gene expression to discrete developmental events remains an elusive challenge in neuroscience, in part because most neural territories are comprised of multiple cell types that mature over extended periods of time. The medial nucleus of the trapezoid body (MNTB) is an attractive vertebrate model system that contains a nearly homogeneous population of neurons, which are innervated by large glutamatergic nerve terminals called calyces of Held (CH). Key steps in maturation of CHs and MNTB neurons, including CH growth and competition, occur very quickly for most cells between postnatal days (P)2 and P6. Therefore, we characterized genome-wide changes in this system, with dense temporal sampling during the first postnatal week. We identified 541 genes whose expression changed significantly between P0–6 and clustered them into eight groups based on temporal expression profiles. Candidate genes from each of the eight profile groups were validated in separate samples by qPCR. Our tissue sample permitted comparison of known glial and neuronal transcripts and revealed that monotonically increasing or decreasing expression profiles tended to be associated with glia and neurons, respectively. Gene ontology revealed enrichment of genes involved in axon pathfinding, cell differentiation, cell adhesion and extracellular matrix. The latter category included elements of perineuronal nets, a prominent feature of MNTB neurons that is morphologically distinct by P6, when CH growth and competition are resolved onto nearly all MNTB neurons. These results provide a genetic framework for investigation of general mechanisms responsible for nerve terminal growth and maturation. PMID:26014473

  3. Conservation and evolutionary modifications of neuroblast expression patterns in insects.

    PubMed

    Biffar, Lucia; Stollewerk, Angelika

    2014-04-01

    One of the major questions in evolutionary developmental neurobiology is how neuronal networks have been adapted to different morphologies and behaviour during evolution. Analyses of neurogenesis in representatives of all arthropod species have revealed evolutionary modifications of various developmental mechanisms. Among others, variations can be seen in mechanisms that are associated with changes in neural progenitor identity, which in turn determines the neuronal subtype of their progeny. Comparative analyses of the molecular processes that underlie the generation of neuronal identity might therefore uncover the steps of evolutionary changes that eventually resulted in modifications in neuronal networks. Here we address this question in the flour beetle Tribolium castaneum by analyzing and comparing the development and expression profile of neural stem cells (neuroblasts) to the published neuroblast map of the fruit fly Drosophila melanogaster. We show that substantial changes in the identity of neuroblasts have occurred during insect evolution. In almost all neuroblasts the relative positions in the ventral hemi-neuromeres are conserved; however, in over half of the neuroblasts the time of formation as well as the gene expression profile has changed. The neuroblast map presented here can be used for future comparative studies on individual neuroblast lineages in D. melanogaster and T. castaneum and additional markers and information on lineages can be added. Our data suggest that evolutionary changes in the expression profile of individual neuroblasts might have contributed to the evolution of neural diversity and subsequently to changes in neuronal networks in arthropod. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Regulation of Gene Expression Patterns in Mosquito Reproduction

    PubMed Central

    Johnson, Lisa; Zhao, Bo; Ha, Jisu; White, Kevin P.; Girke, Thomas; Zou, Zhen; Raikhel, Alexander S.

    2015-01-01

    In multicellular organisms, development, growth and reproduction require coordinated expression of numerous functional and regulatory genes. Insects, in addition to being the most speciose animal group with enormous biological and economical significance, represent outstanding model organisms for studying regulation of synchronized gene expression due to their rapid development and reproduction. Disease-transmitting female mosquitoes have adapted uniquely for ingestion and utilization of the huge blood meal required for swift reproductive events to complete egg development within a 72-h period. We investigated the network of regulatory factors mediating sequential gene expression in the fat body, a multifunctional organ analogous to the vertebrate liver and adipose tissue, of the female Aedes aegypti mosquito. Transcriptomic and bioinformatics analyses revealed that ~7500 transcripts are differentially expressed in four sequential waves during the 72-h reproductive period. A combination of RNA-interference gene-silencing and in-vitro organ culture identified the major regulators for each of these waves. Amino acids (AAs) regulate the first wave of gene activation between 3 h and 12 h post-blood meal (PBM). During the second wave, between 12 h and 36 h, most genes are highly upregulated by a synergistic action of AAs, 20-hydroxyecdysone (20E) and the Ecdysone-Receptor (EcR). Between 36 h and 48 h, the third wave of gene activation—regulated mainly by HR3—occurs. Juvenile Hormone (JH) and its receptor Methoprene-Tolerant (Met) are major regulators for the final wave between 48 h and 72 h. Each of these key regulators also has repressive effects on one or more gene sets. Our study provides a better understanding of the complexity of the regulatory mechanisms related to temporal coordination of gene expression during reproduction. We have detected the novel function of 20E/EcR responsible for transcriptional repression. This study also reveals the previously

  5. Regulation of Gene Expression Patterns in Mosquito Reproduction.

    PubMed

    Roy, Sourav; Saha, Tusar T; Johnson, Lisa; Zhao, Bo; Ha, Jisu; White, Kevin P; Girke, Thomas; Zou, Zhen; Raikhel, Alexander S

    2015-08-01

    In multicellular organisms, development, growth and reproduction require coordinated expression of numerous functional and regulatory genes. Insects, in addition to being the most speciose animal group with enormous biological and economical significance, represent outstanding model organisms for studying regulation of synchronized gene expression due to their rapid development and reproduction. Disease-transmitting female mosquitoes have adapted uniquely for ingestion and utilization of the huge blood meal required for swift reproductive events to complete egg development within a 72-h period. We investigated the network of regulatory factors mediating sequential gene expression in the fat body, a multifunctional organ analogous to the vertebrate liver and adipose tissue, of the female Aedes aegypti mosquito. Transcriptomic and bioinformatics analyses revealed that ~7500 transcripts are differentially expressed in four sequential waves during the 72-h reproductive period. A combination of RNA-interference gene-silencing and in-vitro organ culture identified the major regulators for each of these waves. Amino acids (AAs) regulate the first wave of gene activation between 3 h and 12 h post-blood meal (PBM). During the second wave, between 12 h and 36 h, most genes are highly upregulated by a synergistic action of AAs, 20-hydroxyecdysone (20E) and the Ecdysone-Receptor (EcR). Between 36 h and 48 h, the third wave of gene activation-regulated mainly by HR3-occurs. Juvenile Hormone (JH) and its receptor Methoprene-Tolerant (Met) are major regulators for the final wave between 48 h and 72 h. Each of these key regulators also has repressive effects on one or more gene sets. Our study provides a better understanding of the complexity of the regulatory mechanisms related to temporal coordination of gene expression during reproduction. We have detected the novel function of 20E/EcR responsible for transcriptional repression. This study also reveals the previously

  6. Analysis of gelsolin expression pattern in developing chicken embryo reveals high GSN expression level in tissues of neural crest origin.

    PubMed

    Mazur, Antonina Joanna; Morosan-Puopolo, Gabriela; Makowiecka, Aleksandra; Malicka-Błaszkiewicz, Maria; Nowak, Dorota; Brand-Saberi, Beate

    2016-01-01

    Gelsolin is one of the most intensively studied actin-binding proteins. However, in the literature comprehensive studies of GSN expression during development have not been performed yet in all model organisms. In zebrafish, gelsolin is a dorsalizing factor that modulates bone morphogenetic proteins signaling pathways, whereas knockout of the gelsolin coding gene, GSN is not lethal in murine model. To study the role of gelsolin in development of higher vertebrates, it is crucial to estimate GSN expression pattern during development. Here, we examined GSN expression in the developing chicken embryo. We applied numerous methods to track GSN expression in developing embryos at mRNA and protein level. We noted a characteristic GSN expression pattern. Although GSN transcripts were present in several cell types starting from early developmental stages, a relatively high GSN expression was observed in eye, brain vesicles, midbrain, neural tube, heart tube, and splanchnic mesoderm. In older embryos, we observed a high GSN expression in the cranial ganglia and dorsal root ganglia. A detailed analysis of 10-day-old chicken embryos revealed high amounts of gelsolin especially within the head region: in the olfactory and optic systems, meninges, nerves, muscles, presumptive pituitary gland, and pericytes, but not oligodendrocytes in the brain. Obtained results suggest that GSN is expressed at high levels in some tissues of ectodermal origin including all neural crest derivatives. Additionally, we describe that silencing of GSN expression in brain vesicles leads to altered morphology of the mesencephalon. This implies gelsolin is crucial for chicken brain development.

  7. Ubiquitous expression of selenoprotein N transcripts in chicken tissues and early developmental expression pattern in skeletal muscles.

    PubMed

    Zhang, Jiuli; Li, Jinlong; Zhang, Ziwei; Sun, Bo; Wang, Rihua; Jiang, Zhihui; Li, Shu; Xu, Shiwen

    2012-05-01

    Previous results revealed a ubiquitous expression pattern of selenoprotein N (SelN, SEPN1) in humans, zebrafish, and mouse, suggesting that it plays a potential role during the embryogenesis of these species. However, no information is known about the tissue distribution of SelN and mRNA expression analysis in the muscle tissues during development in birds. We analyzed the mRNA expression of SelN in 26 different tissues of 90-day-old chickens and the expression of SelN in the muscle tissues of 12-day-old chicken embryos and 15-month-old adult chickens by quantitative real-time PCR. The results showed that SelN transcripts were expressed widely in the chicken tissues. Moreover, the expression of SelN mRNA in skeletal muscles was present at a high level in whole embryos and at a lower level in postnatal stages. However, the expression of SelN mRNA in cardiac muscle showed a different expression pattern compared with skeletal muscles. Our data indicate that the expression of the SelN gene in chicken is ubiquitous, suggesting a role of SelN in the development of chick embryo skeletal muscles.

  8. Expression of Programmed Cell Death 1 Ligand 2 (PD-L2) is a Distinguishing Feature of Primary Mediastinal (Thymic) Large B-cell Lymphoma and Associated with PDCD1LG2 Copy Gain

    PubMed Central

    Shi, Min; Roemer, Margaretha GM; Chapuy, Bjoern; Liao, Xiaoyun; Sun, Heather; Pinkus, Geraldine S.; Shipp, Margaret A.; Freeman, Gordon J.; Rodig, Scott J.

    2016-01-01

    Primary mediastinal (thymic) large B-cell lymphoma (PMBL) and diffuse large B-cell lymphoma (DLBCL) are tumors with distinct clinical and molecular characteristics that are difficult to distinguish by histopathological and phenotypic analyses alone. Programmed cell death 1 ligand 2 (PD-L2) is a cell surface protein expressed by activated macrophages and dendritic cells that binds PD-1 on T-cells to inhibit immune responses. Amplification and/or translocations involving chromosome 9p24.1, a region that includes PDCD1LG2 encoding PD-L2, is a common event in PMBL but not DLBCL and suggests that PD-L2 expression might be a distinguishing feature of PMBL. We developed an assay for the immunohistochemical detection of PD-L2 protein in fixed biopsy specimens (PD-L2 IHC) which we applied to a cohort of PMBLs and DLBCLs. For a subset of cases, we correlated the results of PD-L2 IHC with PDCD1LG2 copy number as determined by qPCR. Twenty-three of 32 (72%) PMBLs but only 1 of 37 (3%) DLBCLs were positive by PD-L2 IHC. Among PMBLs with PDCD1LG2 copy number gain, all were positive by PD-L2 IHC. One PMBL without copy number gain was positive by PD-L2 IHC. When expressed in PMBL, PD-L2 was restricted to tumor cells and not detected on intra-tumoral macrophages. We conclude that PD-L2 protein is robustly expressed by the majority of PMBLs but only rare DLBCLs and often associated with PDCD1LG2 copy gain. PD-L2 IHC may serve as a useful ancillary test for distinguishing PMBL from DLBCL and for the rational selection of patients for therapeutic antibodies that inhibit PD-1 signaling. PMID:25025450

  9. Distinct Expression Pattern of a Deafness Gene, KIAA1199, in a Primate Cochlea.

    PubMed

    Hosoya, Makoto; Fujioka, Masato; Okano, Hideyuki; Ogawa, Kaoru

    2016-01-01

    Deafness is one of the most common types of congenital impairments, and at least half of the cases are caused by hereditary mutations. Mutations of the gene KIAA1199 are associated with progressive hearing loss. Its expression is abundant in human cochlea, but interestingly the spatial expression patterns are different between mouse and rat cochleae; the pattern in humans has not been fully investigated. We performed immunohistochemical analysis of a nonhuman primate, common marmoset (Callithrix jacchus), cochlea with a KIAA1199-specific antibody. In the common marmoset cochlea, KIAA1199 protein expression was more widespread than in rodents, with all epithelial cells, including hair cells, expressing KIAA1199. Our results suggest that the primate pattern of KIAA1199 expression is wider in comparison with rodents and may play an essential role in the maintenance of cochlear epithelial cells.

  10. Integrative analysis of lung development-cancer expression associations reveals the roles of signatures with inverse expression patterns.

    PubMed

    Zhang, Chunlong; Li, Chunquan; Xu, Yanjun; Feng, Li; Shang, Desi; Yang, Xinmiao; Han, Junwei; Sun, Zeguo; Li, Yixue; Li, Xia

    2015-05-01

    Recent studies have focused on exploring the associations between organ development and malignant tumors; however, the clinical relevance of the development signatures was inadequately addressed in lung cancer. In this study, we explored the associations between lung development and lung cancer progression by analyzing a total of two development and seven cancer datasets. We identified representative expression patterns (continuously up- and down-regulated) from development and cancer profiles, and inverse pattern associations were observed at both the gene and functional levels. Furthermore, we dissected the biological processes dominating the associations, and found that proliferation and immunity were respectively involved in the two inverse development-cancer expression patterns. Through sub-pathway analysis of the signatures with inverse expression patterns, we finally identified a 13-gene risk signature from the cell cycle sub-pathway, and evaluated its predictive performance for lung cancer patient clinical outcome using independent cohorts. Our findings indicated that the integrative analysis of development and cancer expression patterns provided a framework for identifying effective molecular signatures for clinical utility.

  11. Stochastic Local Distinguishability

    NASA Astrophysics Data System (ADS)

    Bandyopadhyay, Somshubhro; Roy, Anirban; Walgate, Jonathan

    2007-03-01

    We pose the question, ``when is globally available information is also locally available?'', formally as the problem of local state discrimination, and show that the deep qualitative link between local distinguishability and entanglement lies at the level of stochastic rather than deterministic local protocols. We restrict our attention to sets of mutually orthogonal pure quantum states. We define a set of states |ψi> as beingstochastically locally distinguishable if and only if there is a LOCC protocol whereby the parties can conclusively identify a member of the set with some nonzero probability. If a set is stochastically locally distinguishable, then the complete global information is potentially locally available. If not, the physical information encoded by the system can never be completely locally exposed. Our results are proved true for all orthogonal quantum states regardless of their dimensionality or multipartiality. First, we prove that entanglement is a necessary property of any system whose total global information can never be locally accessed. Second, entangled states that form part of an orthogonal basis can never be locally singled out. Completely entangled bases are, always stochastically locally indistinguishable. Third, we prove that any set of three orthogonal states, is stochastically locally distinguishable.

  12. Distinguished Cooperating Teacher Program.

    ERIC Educational Resources Information Center

    Chicago State Univ., IL.

    The Distinguished Cooperating Teacher Program at Chicago State University was developed to train cooperating teachers to supervise student teachers. The program departs from traditional practice by changing the roles of the classroom teacher and the university field supervisor. The supervisor's role becomes that of coordinator while the teacher…

  13. Evolution and Expression Patterns of TCP Genes in Asparagales

    PubMed Central

    Madrigal, Yesenia; Alzate, Juan F.; Pabón-Mora, Natalia

    2017-01-01

    CYCLOIDEA-like genes are involved in the symmetry gene network, limiting cell proliferation in the dorsal regions of bilateral flowers in core eudicots. CYC-like and closely related TCP genes (acronym for TEOSINTE BRANCHED1, CYCLOIDEA, and PROLIFERATION CELL FACTOR) have been poorly studied in Asparagales, the largest order of monocots that includes both bilateral flowers in Orchidaceae (ca. 25.000 spp) and radially symmetrical flowers in Hypoxidaceae (ca. 200 spp). With the aim of assessing TCP gene evolution in the Asparagales, we isolated TCP-like genes from publicly available databases and our own transcriptomes of Cattleya trianae (Orchidaceae) and Hypoxis decumbens (Hypoxidaceae). Our matrix contains 452 sequences representing the three major clades of TCP genes. Besides the previously identified CYC specific core eudicot duplications, our ML phylogenetic analyses recovered an early CIN-like duplication predating all angiosperms, two CIN-like Asparagales-specific duplications and a duplication prior to the diversification of Orchidoideae and Epidendroideae. In addition, we provide evidence of at least three duplications of PCF-like genes in Asparagales. While CIN-like and PCF-like genes have multiplied in Asparagales, likely enhancing the genetic network for cell proliferation, CYC-like genes remain as single, shorter copies with low expression. Homogeneous expression of CYC-like genes in the labellum as well as the lateral petals suggests little contribution to the bilateral perianth in C. trianae. CIN-like and PCF-like gene expression suggests conserved roles in cell proliferation in leaves, sepals and petals, carpels, ovules and fruits in Asparagales by comparison with previously reported functions in core eudicots and monocots. This is the first large scale analysis of TCP-like genes in Asparagales that will serve as a platform for in-depth functional studies in emerging model monocots. PMID:28144250

  14. Evolution and Expression Patterns of TCP Genes in Asparagales.

    PubMed

    Madrigal, Yesenia; Alzate, Juan F; Pabón-Mora, Natalia

    2017-01-01

    CYCLOIDEA-like genes are involved in the symmetry gene network, limiting cell proliferation in the dorsal regions of bilateral flowers in core eudicots. CYC-like and closely related TCP genes (acronym for TEOSINTE BRANCHED1, CYCLOIDEA, and PROLIFERATION CELL FACTOR) have been poorly studied in Asparagales, the largest order of monocots that includes both bilateral flowers in Orchidaceae (ca. 25.000 spp) and radially symmetrical flowers in Hypoxidaceae (ca. 200 spp). With the aim of assessing TCP gene evolution in the Asparagales, we isolated TCP-like genes from publicly available databases and our own transcriptomes of Cattleya trianae (Orchidaceae) and Hypoxis decumbens (Hypoxidaceae). Our matrix contains 452 sequences representing the three major clades of TCP genes. Besides the previously identified CYC specific core eudicot duplications, our ML phylogenetic analyses recovered an early CIN-like duplication predating all angiosperms, two CIN-like Asparagales-specific duplications and a duplication prior to the diversification of Orchidoideae and Epidendroideae. In addition, we provide evidence of at least three duplications of PCF-like genes in Asparagales. While CIN-like and PCF-like genes have multiplied in Asparagales, likely enhancing the genetic network for cell proliferation, CYC-like genes remain as single, shorter copies with low expression. Homogeneous expression of CYC-like genes in the labellum as well as the lateral petals suggests little contribution to the bilateral perianth in C. trianae. CIN-like and PCF-like gene expression suggests conserved roles in cell proliferation in leaves, sepals and petals, carpels, ovules and fruits in Asparagales by comparison with previously reported functions in core eudicots and monocots. This is the first large scale analysis of TCP-like genes in Asparagales that will serve as a platform for in-depth functional studies in emerging model monocots.

  15. Correlating Histone Modification Patterns with Gene Expression Data During Hematopoiesis

    PubMed Central

    Hu, Gangqing; Zhao, Keji

    2014-01-01

    Hematopoietic stem cells (HSC) in mammals are an ideal system to study differentiation. While transcription factors (TFs) control the differentiation of HSCs to distinctive terminal blood cells, accumulating evidence suggests that chromatin structure and modifications constitute another critical layer of gene regulation. Recent genome-wide studies based on next-generation sequencing reveal that histone modifications are linked to gene expression and contribute to hematopoiesis. Here, we briefl y review the bioinformatics aspects for ChIP-Seq and RNA-Seq data analysis with applications to the epigenetic studies of hematopoiesis and provide a practical guide to several basic data analysis methods. PMID:24743998

  16. Patterns of gene expression in the sheep heart during the perinatal period revealed by transcriptomic modeling

    PubMed Central

    Rabaglino, M. Belen; Antolic, Andrew; Wood, Charles E.; Keller-Wood, Maureen

    2015-01-01

    Septa from sheep hearts at 130 days gestation, term, and 14-day-old lambs were used to model the changes in gene expression patterns during the perinatal period using Agilent 15k ovine microarrays. We used Bioconductor for R to model five major patterns of coexpressed genes. Gene ontology and transcription factor analyses using Webgestalt modeled the biological significances and transcription factors of the gene expression patterns. Modeling indicated a decreased expression of genes associated with anatomical development and differentiation during this period, whereas those associated with increased protein synthesis and growth associated with maturation of the endoplasmic reticulum rose to term but did not further increase from the near term expression. Expression of genes associated with cell responsiveness, for example, immune responses, decreased at term but expression returned by postnatal day 14. Changes in genes related to metabolism showed differential substrate-associated patterns: those related to carbohydrate metabolism rose to term and remained stable thereafter, whereas those associated with fatty acid oxidation facility rose throughout the period. The timing of many of these maturational processes was earlier in relation to birth than in the rodent. The importance of the transcription factors, estrogen-related receptors, and v-myc avian myelocytomatosis viral oncogene homolog was also highlighted in the pattern of gene expression during development of the perinatal sheep heart. PMID:26126790

  17. Patterns of gene expression in the sheep heart during the perinatal period revealed by transcriptomic modeling.

    PubMed

    Richards, Elaine M; Rabaglino, M Belen; Antolic, Andrew; Wood, Charles E; Keller-Wood, Maureen

    2015-09-01

    Septa from sheep hearts at 130 days gestation, term, and 14-day-old lambs were used to model the changes in gene expression patterns during the perinatal period using Agilent 15k ovine microarrays. We used Bioconductor for R to model five major patterns of coexpressed genes. Gene ontology and transcription factor analyses using Webgestalt modeled the biological significances and transcription factors of the gene expression patterns. Modeling indicated a decreased expression of genes associated with anatomical development and differentiation during this period, whereas those associated with increased protein synthesis and growth associated with maturation of the endoplasmic reticulum rose to term but did not further increase from the near term expression. Expression of genes associated with cell responsiveness, for example, immune responses, decreased at term but expression returned by postnatal day 14. Changes in genes related to metabolism showed differential substrate-associated patterns: those related to carbohydrate metabolism rose to term and remained stable thereafter, whereas those associated with fatty acid oxidation facility rose throughout the period. The timing of many of these maturational processes was earlier in relation to birth than in the rodent. The importance of the transcription factors, estrogen-related receptors, and v-myc avian myelocytomatosis viral oncogene homolog was also highlighted in the pattern of gene expression during development of the perinatal sheep heart.

  18. BEST: a novel computational approach for comparing gene expression patterns from early stages of Drosophila melanogaster development.

    PubMed Central

    Kumar, Sudhir; Jayaraman, Karthik; Panchanathan, Sethuraman; Gurunathan, Rajalakshmi; Marti-Subirana, Ana; Newfeld, Stuart J

    2002-01-01

    Embryonic gene expression patterns are an indispensable part of modern developmental biology. Currently, investigators must visually inspect numerous images containing embryonic expression patterns to identify spatially similar patterns for inferring potential genetic interactions. The lack of a computational approach to identify pattern similarities is an impediment to advancement in developmental biology research because of the rapidly increasing amount of available embryonic gene expression data. Therefore, we have developed computational approaches to automate the comparison of gene expression patterns contained in images of early stage Drosophila melanogaster embryos (prior to the beginning of germ-band elongation); similarities and differences in gene expression patterns in these early stages have extensive developmental effects. Here we describe a basic expression search tool (BEST) to retrieve best matching expression patterns for a given query expression pattern and a computational device for gene interaction inference using gene expression pattern images and information on the associated genotypes and probes. Analysis of a prototype collection of Drosophila gene expression pattern images is presented to demonstrate the utility of these methods in identifying biologically meaningful matches and inferring gene interactions by direct image content analysis. In particular, the use of BEST searches for gene expression patterns is akin to that of BLAST searches for finding similar sequences. These computational developmental biology methodologies are likely to make the great wealth of embryonic gene expression pattern data easily accessible and to accelerate the discovery of developmental networks. PMID:12524369

  19. Automated annotation of Drosophila gene expression patterns using a controlled vocabulary

    PubMed Central

    Ji, Shuiwang; Sun, Liang; Jin, Rong; Kumar, Sudhir; Ye, Jieping

    2008-01-01

    Motivation: Regulation of gene expression in space and time directs its localization to a specific subset of cells during development. Systematic determination of the spatiotemporal dynamics of gene expression plays an important role in understanding the regulatory networks driving development. An atlas for the gene expression patterns of fruit fly Drosophila melanogaster has been created by whole-mount in situ hybridization, and it documents the dynamic changes of gene expression pattern during Drosophila embryogenesis. The spatial and temporal patterns of gene expression are integrated by anatomical terms from a controlled vocabulary linking together intermediate tissues developed from one another. Currently, the terms are assigned to patterns manually. However, the number of patterns generated by high-throughput in situ hybridization is rapidly increasing. It is, therefore, tempting to approach this problem by employing computational methods. Results: In this article, we present a novel computational framework for annotating gene expression patterns using a controlled vocabulary. In the currently available high-throughput data, annotation terms are assigned to groups of patterns rather than to individual images. We propose to extract invariant features from images, and construct pyramid match kernels to measure the similarity between sets of patterns. To exploit the complementary information conveyed by different features and incorporate the correlation among patterns sharing common structures, we propose efficient convex formulations to integrate the kernels derived from various features. The proposed framework is evaluated by comparing its annotation with that of human curators, and promising performance in terms of F1 score has been reported. Contact: jieping.ye@asu.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:18632750

  20. Nursing frequency alters circadian patterns of mammary gene expression in lactating mice

    USDA-ARS?s Scientific Manuscript database

    Milking frequency impacts lactation in dairy cattle and in rodent models of lactation. The role of circadian gene expression in this process is unknown. The hypothesis tested was that changing nursing frequency alters the circadian patterns of mammary gene expression. Mid-lactation CD1 mice were stu...

  1. Automatic Annotation of Spatial Expression Patterns via Sparse Bayesian Factor Models

    PubMed Central

    Pruteanu-Malinici, Iulian; Mace, Daniel L.; Ohler, Uwe

    2011-01-01

    Advances in reporters for gene expression have made it possible to document and quantify expression patterns in 2D–4D. In contrast to microarrays, which provide data for many genes but averaged and/or at low resolution, images reveal the high spatial dynamics of gene expression. Developing computational methods to compare, annotate, and model gene expression based on images is imperative, considering that available data are rapidly increasing. We have developed a sparse Bayesian factor analysis model in which the observed expression diversity of among a large set of high-dimensional images is modeled by a small number of hidden common factors. We apply this approach on embryonic expression patterns from a Drosophila RNA in situ image database, and show that the automatically inferred factors provide for a meaningful decomposition and represent common co-regulation or biological functions. The low-dimensional set of factor mixing weights is further used as features by a classifier to annotate expression patterns with functional categories. On human-curated annotations, our sparse approach reaches similar or better classification of expression patterns at different developmental stages, when compared to other automatic image annotation methods using thousands of hard-to-interpret features. Our study therefore outlines a general framework for large microscopy data sets, in which both the generative model itself, as well as its application for analysis tasks such as automated annotation, can provide insight into biological questions. PMID:21814502

  2. Genome-wide analysis of spatiotemporal gene expression patterns during early embryogenesis in rice.

    PubMed

    Itoh, Jun-Ichi; Sato, Yutaka; Sato, Yutaka; Hibara, Ken-Ichiro; Shimizu-Sato, Sae; Kobayashi, Hiromi; Takehisa, Hinako; Sanguinet, Karen A; Namiki, Nobukazu; Nagamura, Yoshiaki

    2016-04-01

    Embryogenesis in rice is different from that of most dicotolydonous plants in that it shows a non-stereotypic cell division pattern, formation of dorsal-ventral polarity, and endogenous initiation of the radicle. To reveal the transcriptional features associated with developmental events during rice early embryogenesis, we used microarray analysis coupled with laser microdissection to obtain both spatial and temporal transcription profiles. Our results allowed us to determine spatial expression foci for each expressed gene in the globular embryo, which revealed the importance of phytohormone-related genes and a suite of transcription factors to early embryogenesis. Our analysis showed the polarized expression of a small number of genes along the apical-basal and dorsal-ventral axes in the globular embryo, which tended to fluctuate in later developmental stages. We also analyzed gene expression patterns in the early globular embryo and how this relates to expression in embryonic organs at later stages. We confirmed the accuracy of the expression patterns found by microarray analysis of embryo subdomains using in situ hybridization. Our study identified homologous genes from Arabidopsis thaliana with known functions in embryogenesis in addition to unique and uncharacterized genes that show polarized expression patterns during embryogenesis. The results of this study are presented in a database to provide a framework for spatiotemporal gene expression during rice embryogenesis, to serve as a resource for future functional analysis of genes, and as a basis for comparative studies of plant embryogenesis.

  3. Dissecting sources of quantitative gene expression pattern divergence between Drosophila species

    PubMed Central

    Wunderlich, Zeba; Bragdon, Meghan D; Eckenrode, Kelly B; Lydiard-Martin, Tara; Pearl-Waserman, Sivanne; DePace, Angela H

    2012-01-01

    Gene expression patterns can diverge between species due to changes in a gene's regulatory DNA or changes in the proteins, e.g., transcription factors (TFs), that regulate the gene. We developed a modeling framework to uncover the sources of expression differences in blastoderm embryos of three Drosophila species, focusing on the regulatory circuit controlling expression of the hunchback (hb) posterior stripe. Using this framework and cellular-resolution expression measurements of hb and its regulating TFs, we found that changes in the expression patterns of hb's TFs account for much of the expression divergence. We confirmed our predictions using transgenic D. melanogaster lines, which demonstrate that this set of orthologous cis-regulatory elements (CREs) direct similar, but not identical, expression patterns. We related expression pattern differences to sequence changes in the CRE using a calculation of the CRE's TF binding site content. By applying this calculation in both the transgenic and endogenous contexts, we found that changes in binding site content affect sensitivity to regulating TFs and that compensatory evolution may occur in circuit components other than the CRE. PMID:22893002

  4. Dissecting sources of quantitative gene expression pattern divergence between Drosophila species.

    PubMed

    Wunderlich, Zeba; Bragdon, Meghan D; Eckenrode, Kelly B; Lydiard-Martin, Tara; Pearl-Waserman, Sivanne; DePace, Angela H

    2012-01-01

    Gene expression patterns can diverge between species due to changes in a gene's regulatory DNA or changes in the proteins, e.g., transcription factors (TFs), that regulate the gene. We developed a modeling framework to uncover the sources of expression differences in blastoderm embryos of three Drosophila species, focusing on the regulatory circuit controlling expression of the hunchback (hb) posterior stripe. Using this framework and cellular-resolution expression measurements of hb and its regulating TFs, we found that changes in the expression patterns of hb's TFs account for much of the expression divergence. We confirmed our predictions using transgenic D. melanogaster lines, which demonstrate that this set of orthologous cis-regulatory elements (CREs) direct similar, but not identical, expression patterns. We related expression pattern differences to sequence changes in the CRE using a calculation of the CRE's TF binding site content. By applying this calculation in both the transgenic and endogenous contexts, we found that changes in binding site content affect sensitivity to regulating TFs and that compensatory evolution may occur in circuit components other than the CRE.

  5. Temporal expression patterns of timeless in vg and cry(b) mutants of Drosophila melanogaster.

    PubMed

    Suthakar, G; Subramanian, P; Manivasagam, T

    2005-04-01

    The temporal expression patterns of timeless (tim) in Drosophila melanogaster at various time points were studied in intestine and salivary gland of wild type (WT), vestigial (vg) and cryptochrome-absent (cry(b)) mutants under 12 hr:12 hr white light:darkness (LD) and 12 hr:12 hr blue light (450 nm):darkness (BD) conditions. At ZT 06 and ZT 10, tim expression was almost nil and at ZT 18 and ZT 22, the expression was most pronounced in WT and mutants, when compared to other time points. As vg flies have greatly reduced wings, their gross locomotor activity was poorer and levels of tim expression were also least than WT flies. The weaker expression of tim in cry(b) flies suggested the significant role of blue light photoreceptor cryptochrome for a stronger synchronization of circadian clock. The expression patterns of tim in the salivary gland of larvae further suggested the presence of peripheral oscillators during the developmental stages.

  6. Expression patterns of genes critical for BMP signaling pathway in developing human primary tooth germs.

    PubMed

    Dong, Xiuqing; Shen, Bin; Ruan, Ningsheng; Guan, Zhen; Zhang, Yanding; Chen, YiPing; Hu, Xuefeng

    2014-12-01

    The developing murine tooth has been used as an excellent model system to study the molecular mechanism of organ development and regeneration. While the expression patterns of numerous regulatory genes have been examined and their roles have begun to be revealed in the developing murine tooth, little is known about gene expression and function in human tooth development. In order to unveil the molecular mechanisms that regulate human tooth morphogenesis, we examined the expression patterns of the major BMP signaling pathway molecules in the developing human tooth germ at the cap and bell stages by in situ hybridization, immunohistochemistry, and real-time RT-PCR. Expression of BMP ligands and antagonist, including BMP2, BMP3, BMP4, BMP7, and NOOGGIN, exhibited uniform patterns in the tooth germs of incisor and molar at the cap and bell stages with stronger expression in the inner dental epithelium than that in the dental mesenchyme. Both type I and type II BMP receptors were present in widespread expression pattern in the whole-enamel organ and the dental mesenchyme with the strongest expression in inner dental epithelium at the cap and bell stages. SMAD4 and SMAD1/5/8 showed an expression pattern similar to that of BMP ligands with more intensive signals in the inner dental epithelium. Despite some unique and distinct patterns as compared to the mouse, the intensive expression of BMP signaling pathway molecules in the developing human tooth strongly suggests conserved functions of BMP signaling during human odontogenesis, such as in mediating tissue interactions and regulating differentiation and organization of odontogenic tissues. Our results provide an important set of documents for studying molecular regulatory mechanisms underlying tooth development and regeneration in humans.

  7. Diffuse growth pattern affects E-cadherin expression in invasive breast cancer.

    PubMed

    Brinck, Ulrich; Jacobs, Susanne; Neuss, Michael; Tory, Kalman; Rath, Werner; Kulle, Bettina; Füzesi, Laszlo

    2004-01-01

    We investigated the correlations between growth patterns and E-cadherin expression by immunohistochemistry and the presence of mutations of exons 6-10 of the E-cadherin gene by PCR-SSCP, in 79 cases of invasive lobular and ductal breast cancer. E-cadherin expression showed a tendency to be lower in lobular than in ductal carcinomas (p=0.064). In 60% of lobular carcinomas the diffuse growth pattern and in 72% of ductal carcinomas the compact growth pattern predominated. E-cadherin expression was significantly lower in diffuse than in compact tumor area (p<0.001) and not related to carcinoma type when it was considered in tumor areas with either diffuse (p=0.278) or compact (p=0.128) growth pattern. No mutations were detected. In conclusion, loss of E-cadherin expression is related to an increase of diffuse growth pattern in both lobular and ductal types of breast cancer, and the differential proportions of growth patterns in both tumor types cause the tendency for lower E-cadherin expression in the lobular type.

  8. Facial expression recognition based on improved local ternary pattern and stacked auto-encoder

    NASA Astrophysics Data System (ADS)

    Wu, Yao; Qiu, Weigen

    2017-08-01

    In order to enhance the robustness of facial expression recognition, we propose a method of facial expression recognition based on improved Local Ternary Pattern (LTP) combined with Stacked Auto-Encoder (SAE). This method uses the improved LTP extraction feature, and then uses the improved depth belief network as the detector and classifier to extract the LTP feature. The combination of LTP and improved deep belief network is realized in facial expression recognition. The recognition rate on CK+ databases has improved significantly.

  9. Modeling of gene expression pattern alteration by p,p′-DDE and dieldrin in largemouth bass

    USGS Publications Warehouse

    Garcia-Reyero, Natalia; Barber, David; Gross, Timothy; Denslow, Nancy

    2006-01-01

    In this study, largemouth bass (LMB) were subchronically exposed to p,p′-DDE or dieldrin in their diet to evaluate the effect of exposure on expression of genes involved in reproduction and steroid homeostasis. Using real-time PCR, we detected a different gene expression pattern for each OCP, suggesting that they each affect LMB in a different way. We also detected a different expression pattern among sexes, suggesting that sexes are affected differently by OCPs perhaps reflecting the different adaptive responses of each sex to dysregulation caused by OCP exposure.

  10. Modeling of gene expression pattern alteration by p,p'-DDE and dieldrin in largemouth bass.

    PubMed

    Garcia-Reyero, Natàlia; Barber, David; Gross, Timothy; Denslow, Nancy

    2006-07-01

    In this study, largemouth bass (LMB) were subchronically exposed to p,p'-DDE or dieldrin in their diet to evaluate the effect of exposure on expression of genes involved in reproduction and steroid homeostasis. Using real-time PCR, we detected a different gene expression pattern for each OCP, suggesting that they each affect LMB in a different way. We also detected a different expression pattern among sexes, suggesting that sexes are affected differently by OCPs perhaps reflecting the different adaptive responses of each sex to dysregulation caused by OCP exposure.

  11. Modeling of gene expression pattern alteration by p,p′-DDE and dieldrin in largemouth bass

    PubMed Central

    Garcia-Reyero, Natàlia; Barber, David; Gross, Timothy; Denslow, Nancy

    2007-01-01

    In this study, largemouth bass (LMB) were subchronically exposed to p,p′-DDE or dieldrin in their diet to evaluate the effect of exposure on expression of genes involved in reproduction and steroid homeostasis. Using real-time PCR, we detected a different gene expression pattern for each OCP, suggesting that they each affect LMB in a different way. We also detected a different expression pattern among sexes, suggesting that sexes are affected differently by OCPs perhaps reflecting the different adaptive responses of each sex to dysregulation caused by OCP exposure. PMID:16707152

  12. The importance of basidiomycetous fungi cultured from the sputum of chronic idiopathic cough: a study to determine the existence of recognizable clinical patterns to distinguish CIC from non-CIC.

    PubMed

    Ogawa, Haruhiko; Fujimura, Masaki; Takeuchi, Yasuo; Makimura, Koichi

    2009-10-01

    Recently we have reported 5 cases of allergic fungal cough (AFC), which is intractable and is characterized by sensitization to one of basidiomycetous fungus. Because AFC shows good clinical response to antifungal drugs, diagnosing AFC in patients with CIC may lead to the consequent management of CIC. Therefore, we determined the incidence of CIC among our hospital patients, and the frequency of BM fungi in sputum samples collected from patients with CIC. Furthermore we evaluated whether or not a recognizable clinical pattern that distinguishes CIC from non-CIC exists. The medical records of 70 patients complaining of chronic cough who were referred to our hospital for diagnosis and treatment were analyzed retrospectively. The primary diagnoses were CIC (27.0%), cough-variant asthma (30.0%), atopic cough (24.3%), sinobronchial syndrome (8.6%), cough-predominant asthma (7.1%), gastro-esophageal reflux (1.4%), and others (1.4%). In CIC patients, the median age, proportion of females, and frequency of acute upper respiratory tract infection did not differ significantly from those in non-CIC patients. CIC patients had a longer median duration of cough (11.0 months vs. 3.5 months). The positive ratio of BM cultured from the sputa of CIC patients (62.5%) was significantly (p=0.0061) higher than that of non-CIC patients (16.7%). The existence of BM fungi in induced sputum may be an important factor for distinguishing the clinical manifestation of CIC from that of non-CIC. The clinical approach from the aspect of fungal allergy may serve as a clue that may aid in the successful management of CIC.

  13. Systematic variation in gene expression patterns in human cancer cell lines

    SciTech Connect

    Ross, Douglas T.; Scherf, Uwe; Eisen, Michael B.; Perou, Charles M.; Rees, Christian; Spellman, Paul; Iyer, Vishwanath; Jeffrey, Stefanie S.; Van de Rijn, Matt; Waltham, Mark; Pergamenschikov, Alexander; Lee, Jeffrey C.F.; Lashkari, Deval; Shalon, Dari; Myers, Timothy G.; Weinstein, John N.; Botstein, David; Brown, Patrick O.

    2000-01-01

    We used cDNA micro arrays to explore the variation in expression of approximately 8,000 unique genes among the 60 cell lines used in the National Cancer Institute s screen for anti-cancer drugs. Classification of the cell lines based solely on the observed patterns of gene expression revealed a correspondence to the ostensible origins of the tumors from which the cell lines were derived. The consistent relationship between the gene expression patterns and the tissue of origin allowed us to recognize outliers whose previous classification appeared incorrect. Specific features of the gene expression patterns appeared to be related to physiological properties of the cell lines, such as their doubling time in culture, drug metabolism or the interferon response. Comparison of gene expression patterns in the cell lines to those observed in normal breast tissue or in breast tumor specimens revealed features of the expression patterns in the tumors that had recognizable counterparts in specific cell lines, reflecting the tumor, stromal and inflammatory components of the tumor tissue. These results provided a novel molecular characterization of this important group of human cell lines and their relationships to tumors in vivo.

  14. Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain

    PubMed Central

    Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

    2013-01-01

    An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain. PMID:23440889

  15. Murine Brca2: Sequence, map position, and expression pattern

    SciTech Connect

    Sharan, S.K.; Bradley, A.

    1997-03-01

    Mutations in the human BRCA2 gene are responsible for about 45% of hereditary early onset breast cancer. Recently, the human BRCA2 gene was cloned, and several germline mutations were identified. Here we describe the cloning of the mouse homologue of BRCA2. The mouse cDNA sequence predicts a 3328-amino-acid Brca2 protein, 90 amino acids shorter than the human protein. The overall identity between the mouse and the human proteins is 59%, while the similarity is 72%. At the nucleotide level the homology is 74%. By comparing the amino acid sequences of the two homologues we have identified five highly conserved novel domains that may be functionally significant. Brca2 has been mapped to the distal end of mouse chromosome 5, a region of the mouse genome that contains other genes that also map to human chromosome 13q12-q13, confirming the conservation of this linkage group between the two species. Expression of Brca2 was detected in midgestation embryos and adult testis, thymus, and ovary. 21 refs., 5 figs.

  16. Patterning and Nuclear β-Catenin Expression in the Colonic Adenoma-Carcinoma Sequence

    PubMed Central

    Kirchner, Thomas; Brabletz, Thomas

    2000-01-01

    Patterning is a process by which ordered arrangements of cells and tissue structure are attained. The term derived from developmental biology is also useful for the study of colonic carcinogenesis, in which the patterning of neoplastic tubules is necessary for properties of growth, invasion, and metastasis. Interestingly the nuclear expression and transcriptional activity of β-catenin, a major oncoprotein in colonic carcinogenesis, is decisive for the first patterning of a tubule in embryogenesis, which creates the primitive gut and is called the gastrulation. Thus, basic patternings of embryogenesis and carcinogenesis might be linked. To test this hypothesis we compared morphological patterns and immunohistochemical β-catenin stainings in colonic adenomas and adenocarcinomas with the gastrulation steps. Two analogies were found: 1) the patterning of invasion with reconstruction in adenocarcinomas corresponded to the epithelio-mesenchymal transition, ingression, and rearrangement of cells during the first phase of gastrulation; and 2) the patterning of tubular branching in adenomas and adenocarcinomas resembled the endodermal invagination during the second phase. The intratumorous distribution and intensity of nuclear β-catenin expression was significantly correlated with the two patternings, similar to the findings in gastrulation. The results indicate microenvironmental regulations of nuclear β-catenin expression and a return of neoplastic cells to embryonic transcriptional susceptibilities during colonic carcinogenesis. PMID:11021815

  17. ALDH1 and podoplanin expression patterns predict the risk of malignant transformation in oral leukoplakia

    PubMed Central

    Habiba, Umma; Hida, Kyoko; Kitamura, Tetsuya; Matsuda, Aya Yanagawa; Higashino, Fumihiro; Ito, Yoichi M.; Ohiro, Yoichi; Totsuka, Yasunori; Shindoh, Masanobu

    2017-01-01

    Oral leukoplakia (OL) is a clinically diagnosed preneoplastic lesion of the oral cavity with an increased oral cancer risk. However, the risk of malignant transformation is still difficult to assess. The objective of the present study was to examine the expression patterns of aldehyde dehydrogenase 1 (ALDH1) and podoplanin in OL, and to determine their roles in predicting oral cancer development. In the present study, the expression patterns of ALDH1 and podoplanin were determined in samples from 79 patients with OL. The association between protein expression and clinicopathological parameters, including oral cancer-free survival, was analyzed during a mean follow-up period of 3.4 years. Expression of ALDH1 and podoplanin was observed in 61 and 67% patients, respectively. Kaplan-Meier analysis demonstrated that the expression of the proteins was correlated with the risk of progression to oral cancer. Multivariate analysis revealed that expression of ALDH1 and podoplanin was associated with 3.02- and 2.62-fold increased risk of malignant transformation, respectively. The malignant transformation risk of OL was considerably higher in cases with expression of both proteins. Point-prevalence analysis revealed that 66% of patients with co-expression of ALDH1 and podoplanin developed oral cancer. Taken together, our data indicate that ALDH1 and podoplanin expression patterns in OL are associated with oral cancer development, suggesting that ALDH1 and podoplanin may be useful biomarkers to identify OL patients with a substantially high oral cancer risk. PMID:28123562

  18. ALDH1 and podoplanin expression patterns predict the risk of malignant transformation in oral leukoplakia.

    PubMed

    Habiba, Umma; Hida, Kyoko; Kitamura, Tetsuya; Matsuda, Aya Yanagawa; Higashino, Fumihiro; Ito, Yoichi M; Ohiro, Yoichi; Totsuka, Yasunori; Shindoh, Masanobu

    2017-01-01

    Oral leukoplakia (OL) is a clinically diagnosed preneoplastic lesion of the oral cavity with an increased oral cancer risk. However, the risk of malignant transformation is still difficult to assess. The objective of the present study was to examine the expression patterns of aldehyde dehydrogenase 1 (ALDH1) and podoplanin in OL, and to determine their roles in predicting oral cancer development. In the present study, the expression patterns of ALDH1 and podoplanin were determined in samples from 79 patients with OL. The association between protein expression and clinicopathological parameters, including oral cancer-free survival, was analyzed during a mean follow-up period of 3.4 years. Expression of ALDH1 and podoplanin was observed in 61 and 67% patients, respectively. Kaplan-Meier analysis demonstrated that the expression of the proteins was correlated with the risk of progression to oral cancer. Multivariate analysis revealed that expression of ALDH1 and podoplanin was associated with 3.02- and 2.62-fold increased risk of malignant transformation, respectively. The malignant transformation risk of OL was considerably higher in cases with expression of both proteins. Point-prevalence analysis revealed that 66% of patients with co-expression of ALDH1 and podoplanin developed oral cancer. Taken together, our data indicate that ALDH1 and podoplanin expression patterns in OL are associated with oral cancer development, suggesting that ALDH1 and podoplanin may be useful biomarkers to identify OL patients with a substantially high oral cancer risk.

  19. Expression Profile of the Schistosoma japonicum Degradome Reveals Differential Protease Expression Patterns and Potential Anti-schistosomal Intervention Targets

    PubMed Central

    Liu, Shuai; Cai, Pengfei; Piao, Xianyu; Hou, Nan; Zhou, Xiaosu; Wu, Chuang; Wang, Heng; Chen, Qijun

    2014-01-01

    Blood fluke proteases play pivotal roles in the processes of invasion, nutrition acquisition, immune evasion, and other host-parasite interactions. Hundreds of genes encoding putative proteases have been identified in the recently published schistosome genomes. However, the expression profiles of these proteases in Schistosoma species have not yet been systematically analyzed. We retrieved and culled the redundant protease sequences of Schistosoma japonicum, Schistosoma mansoni, Echinococcus multilocularis, and Clonorchis sinensis from public databases utilizing bioinformatic approaches. The degradomes of the four parasitic organisms and Homo sapiens were then comparatively analyzed. A total of 262 S. japonicum protease sequences were obtained and the expression profiles generated using whole-genome microarray. Four main clusters of protease genes with different expression patterns were identified: proteases up-regulated in hepatic schistosomula and adult worms, egg-specific or predominantly expressed proteases, cercaria-specific or predominantly expressed proteases, and constantly expressed proteases. A subset of protease genes with different expression patterns were further validated using real-time quantitative PCR. The present study represents the most comprehensive analysis of a degradome in Schistosoma species to date. These results provide a firm foundation for future research on the specific function(s) of individual proteases and may help to refine anti-proteolytic strategies in blood flukes. PMID:25275570

  20. Regional expression patterns of taste receptors and gustducin in the mouse tongue.

    PubMed

    Kim, Mi-Ryung; Kusakabe, Yuko; Miura, Hirohito; Shindo, Yoichiro; Ninomiya, Yuzo; Hino, Akihiro

    2003-12-12

    In order to understand differences in taste sensitivities of taste bud cells between the anterior and posterior part of tongue, it is important to analyze the regional expression patterns of genes related to taste signal transduction on the tongue. Here we examined the expression pattern of a taste receptor family, the T1r family, and gustducin in circumvallate and fungiform papillae of the mouse tongue using double-labeled in situ hybridization. Each member of the T1r family was expressed in both circumvallate and fungiform papillae with some differences in their expression patterns. The most striking difference between fungiform and circumvallate papillae was observed in their co-expression patterns of T1r2, T1r3, and gustducin. T1r2-positive cells in fungiform papillae co-expressed T1r3 and gustducin, whereas T1r2 and T1r3 double-positive cells in circumvallate papillae merely expressed gustducin. These results suggested that in fungiform papillae, gustducin might play a role in the sweet taste signal transduction cascade mediated by a sweet receptor based on the T1r2 and T1r3 combination, in fungiform papillae.

  1. Analysis of cCx39 expression pattern during chick development.

    PubMed

    Nicotra, Annalisa; Cicirata, Federico; Martinez, Salvador

    2004-02-20

    The present study reports the expression pattern of connexin39 (cCx39) in chick embryos at different stages of central nervous system development. We examined the expression between HH17 and HH40 developmental stages of chicken embryos by in situ hybridization (ISH) technique. Connexin39 was first expressed at HH17. It stained neuroepithelial cells in the optic (OV) and telencephalic (TEL) vesicles, plus in the superficial mesenchyme of the two rostral branchial arches (maxilar and mandibular). These cells probably originated from the neural crest. This expression pattern changed drastically between stages HH17 and HH23, while it showed relatively little modifications from HH23 to HH29. At these times, connexin39 was expressed in three regions: the telencephalic vesicle, the diencephalon and the isthmus. At later stages, HH35 and HH40, connexin39 was mainly expressed in the ventricular epithelium and three cell layers of the stratum griseum and fibrosum superficialis (SGFS) in the optic tectum, as well as in granular and nuclear cells in the cerebellum. In conclusion, the expression pattern of connexin39 in embryonic nervous system is dynamic. This pattern is different from, and in some aspects complementary to, those showed by other connexins during brain development.

  2. Expression differences of anthocyanin biosynthesis genes reveal regulation patterns for red pear coloration.

    PubMed

    Yang, Ya-nan; Yao, Gai-fang; Zheng, Danman; Zhang, Shao-ling; Wang, Chao; Zhang, Ming-yue; Wu, Jun

    2015-02-01

    This research reveals the different expression patterns of anthocyanin biosynthesis enzyme genes and transcription factors in six red-skinned pear cultivars with different genetic backgrounds. Skin color is an important feature of pear fruits, with red skin generally attracting consumers. However, great differences of coloration exist in different pear cultivars. To elucidate the characteristics of pigmentation in pear cultivars with different genetic backgrounds, six cultivars, belonging to P. communis, P. pyrifolia, P. ussuriensis, P. bretschneideri, and a hybrid of P. communis × P. pyrifolia, were used to detect pigment concentrations, expressions of seven anthocyanin biosynthesis enzyme genes, and three related transcription factor genes. Results showed that the occidental pears 'Starkrimson' and 'Red Bartlett' colored at the beginning of fruit setting, but color decreased with fruit maturity; the other four cultivars showed low anthocyanin accumulations and the contents increased during fruit development, but also decreased at later stages. The expression patterns of genes encoding enzymes indicated that ANS and UFGT were decisive genes for anthocyanin biosynthesis for red-skinned pear, and their different expressions led to the coloration differences between occidental and oriental pears. The expression patterns of transcription factors indicated that the different co-expression of MYB10 and bHLH33 genes and the different expressions of WD40 are involved in the differential regulation mechanisms of anthocyanin biosynthesis and coloration pattern between occidental and oriental pears.

  3. Gene Expression Patterns Associated With Histopathology in Toxic Liver Fibrosis.

    PubMed

    Ippolito, Danielle L; AbdulHameed, Mohamed Diwan M; Tawa, Gregory J; Baer, Christine E; Permenter, Matthew G; McDyre, Bonna C; Dennis, William E; Boyle, Molly H; Hobbs, Cheryl A; Streicker, Michael A; Snowden, Bobbi S; Lewis, John A; Wallqvist, Anders; Stallings, Jonathan D

    2016-01-01

    Toxic industrial chemicals induce liver injury, which is difficult to diagnose without invasive procedures. Identifying indicators of end organ injury can complement exposure-based assays and improve predictive power. A multiplexed approach was used to experimentally evaluate a panel of 67 genes predicted to be associated with the fibrosis pathology by computationally mining DrugMatrix, a publicly available repository of gene microarray data. Five-day oral gavage studies in male Sprague Dawley rats dosed with varying concentrations of 3 fibrogenic compounds (allyl alcohol, carbon tetrachloride, and 4,4'-methylenedianiline) and 2 nonfibrogenic compounds (bromobenzene and dexamethasone) were conducted. Fibrosis was definitively diagnosed by histopathology. The 67-plex gene panel accurately diagnosed fibrosis in both microarray and multiplexed-gene expression assays. Necrosis and inflammatory infiltration were comorbid with fibrosis. ANOVA with contrasts identified that 51 of the 67 predicted genes were significantly associated with the fibrosis phenotype, with 24 of these specific to fibrosis alone. The protein product of the gene most strongly correlated with the fibrosis phenotype PCOLCE (Procollagen C-Endopeptidase Enhancer) was dose-dependently elevated in plasma from animals administered fibrogenic chemicals (P < .05). Semiquantitative global mass spectrometry analysis of the plasma identified an additional 5 protein products of the gene panel which increased after fibrogenic toxicant administration: fibronectin, ceruloplasmin, vitronectin, insulin-like growth factor binding protein, and α2-macroglobulin. These results support the data mining approach for identifying gene and/or protein panels for assessing liver injury and may suggest bridging biomarkers for molecular mediators linked to histopathology.

  4. Extraction and comparison of gene expression patterns from 2D RNA in situ hybridization images.

    PubMed

    Mace, Daniel L; Varnado, Nicole; Zhang, Weiping; Frise, Erwin; Ohler, Uwe

    2010-03-15

    Recent advancements in high-throughput imaging have created new large datasets with tens of thousands of gene expression images. Methods for capturing these spatial and/or temporal expression patterns include in situ hybridization or fluorescent reporter constructs or tags, and results are still frequently assessed by subjective qualitative comparisons. In order to deal with available large datasets, fully automated analysis methods must be developed to properly normalize and model spatial expression patterns. We have developed image segmentation and registration methods to identify and extract spatial gene expression patterns from RNA in situ hybridization experiments of Drosophila embryos. These methods allow us to normalize and extract expression information for 78,621 images from 3724 genes across six time stages. The similarity between gene expression patterns is computed using four scoring metrics: mean squared error, Haar wavelet distance, mutual information and spatial mutual information (SMI). We additionally propose a strategy to calculate the significance of the similarity between two expression images, by generating surrogate datasets with similar spatial expression patterns using a Monte Carlo swap sampler. On data from an early development time stage, we show that SMI provides the most biologically relevant metric of comparison, and that our significance testing generalizes metrics to achieve similar performance. We exemplify the application of spatial metrics on the well-known Drosophila segmentation network. A Java webstart application to register and compare patterns, as well as all source code, are available from: http://tools.genome.duke.edu/generegulation/image_analysis/insitu uwe.ohler@duke.edu Supplementary data are available at Bioinformatics online.

  5. USE OF GENE EXPRESSION ANALYSIS INCORPORATING OPERON-TRANSCRIPTIONAL COUPLING AND TOXICANT DOSE RESPONSE TO DISTINGUISH AMONG STRUCTURAL HOMOLOGUES OF MX

    EPA Science Inventory

    We recently described a general method that can improve microarray analysis of toxicant-exposed cells that uses the intrinsic power of transcriptional coupling and toxicant concentration-expression response data. In this analysis, we characterized changes in global gene expressio...

  6. Two-Photon Intravital Multicolor Imaging Combined with Inducible Gene Expression to Distinguish Metastatic Behavior of Breast Cancer Cells In Vivo

    PubMed Central

    Le Dévédec, Sylvia E.; Lalai, Reshma; Pont, Chantal; de Bont, Hans

    2010-01-01

    Purpose The aim of this study is to use multicolor intravital imaging together with an inducible cell model to compare metastatic behavior of control and genetically modified breast cancer cell populations within the intact primary tumor of a mouse. Procedure GFP-MTLn3-ErbB1 cells were generated with doxycycline-regulated conditional transgene expression using lentiviral TREAutoR3-cyan fluorescent protein (CFP). CFP expression together with tumor cell motility is monitored in vitro and in vivo. Results Effective and tight control of doxycycline-induced CFP expression was observed both in vitro and in vivo. Intravital multiphoton microscopy on intact orthotopic tumors allowed a clear discrimination between GFP-only and (GFP + CFP) cell populations, which enables direct comparison of the motility behavior of two different cell populations in the same microenvironment in vivo. Conclusions This system is robust and versatile for conditional gene expression and can be used to study the role of individual candidate metastasis genes in vitro and in vivo. This technology will allow investigations of cellular events in cancer metastasis and in particular intravasation within a primary tumor. Electronic supplementary material The online version of this article (doi:10.1007/s11307-010-0307-z) contains supplementary material, which is available to authorized users. PMID:20396956

  7. USE OF GENE EXPRESSION ANALYSIS INCORPORATING OPERON-TRANSCRIPTIONAL COUPLING AND TOXICANT DOSE RESPONSE TO DISTINGUISH AMONG STRUCTURAL HOMOLOGUES OF MX

    EPA Science Inventory

    We recently described a general method that can improve microarray analysis of toxicant-exposed cells that uses the intrinsic power of transcriptional coupling and toxicant concentration-expression response data. In this analysis, we characterized changes in global gene expressio...

  8. Pdx1 level defines pancreatic gene expression pattern and cell lineage differentiation.

    PubMed

    Wang, H; Maechler, P; Ritz-Laser, B; Hagenfeldt, K A; Ishihara, H; Philippe, J; Wollheim, C B

    2001-07-06

    The absence of Pdx1 and the expression of brain-4 distinguish alpha-cells from other pancreatic endocrine cell lineages. To define the transcription factor responsible for pancreatic cell differentiation, we employed the reverse tetracycline-dependent transactivator system in INS-I cell-derived subclones INSralphabeta and INSrbeta to achieve tightly controlled and conditional expression of wild type Pdx1 or its dominant-negative mutant, as well as brain-4. INSralphabeta cells express not only insulin but also glucagon and brain-4, while INSrbeta cells express only insulin. Overexpression of Pdx1 eliminated glucagon mRNA and protein in INSralphabeta cells and promoted the expression of beta-cell-specific genes in INSrbeta cells. Induction of dominant-negative Pdx1 in INSralphabeta cells resulted in differentiation of insulin-producing beta-cells into glucagon-containing alpha-cells without altering brain4 expression. Loss of Pdx1 function alone in INSrbeta cells, which do not express endogenous brain-4 and glucagon, was also sufficient to abolish the expression of genes restricted to beta-cells and to cause alpha-cell differentiation. In contrast, induction of brain-4 in INSrbeta cells initiated detectable expression of glucagon but did not affect beta-cell-specific gene expression. In conclusion, Pdx1 confers the expression of pancreatic beta-cell-specific genes, such as genes encoding insulin, islet amyloid polypeptide, Glut2, and Nkx6.1. Pdx1 defines pancreatic cell lineage differentiation. Loss of Pdx1 function rather than expression of brain4 is a prerequisite for alpha-cell differentiation.

  9. Mucin genes have different expression patterns in healthy and diseased upper airway mucosa.

    PubMed

    Martínez-Antón, A; Debolós, C; Garrido, M; Roca-Ferrer, J; Barranco, C; Alobid, I; Xaubet, A; Picado, C; Mullol, J

    2006-04-01

    Mucus hyper-secretion is a feature of several airways diseases such as chronic rhinosinusitis, asthma, and cystic fibrosis (CF). Since mucins are major components of mucus, the knowledge of their distribution and regulation in nasal tissues is likely to improve mucus hyper-secretion therapy. The aim of this study was to evaluate and compare mucin gene expression at epithelial and glandular levels, and to identify potential mucin expression patterns for specific upper airways pathologies. Immunohistochemistry for MUC1, MUC2, and MUC4-MUC8 mucins was performed on healthy nasal mucosa (NM; n=12), bilateral nasal polyps (NP; n=38), NP from CF patients (n=10), and antrochoanal (AC) polyps (n=11). MUC2, MUC4, MUC5AC, and MUC6 mRNA expression were also analysed by in situ hybridization. MUC1, MUC4, and MUC5AC mucins were highly expressed in the epithelium and their expression pattern was similar in all NP types, MUC1 and MUC4 being increased and MUC5AC decreased compared with NM. MUC8 was highly detected at both epithelial and glandular levels with marked variability between groups. MUC5B was mainly detected in glands and the expression in all polyp types was higher than in NM. Moreover, MUC5B expression was higher in NP epithelia from CF patients than in bilateral NP and healthy NM. Although MUC2 expression was low, especially in AC polyps, it was detected in most samples. In NM, MUC6 and MUC7 were scarcely detected and MUC7 expression was restricted to glands. These results suggest that NP have a different pattern of mucin expression than healthy NM and that CF polyps (increased MUC5B) and AC polyps (decreased MUC2) have a different mucin expression pattern than bilateral NP.

  10. Diversity of Reporter Expression Patterns in Transgenic Mouse Lines Targeting Corticotropin-Releasing Hormone-Expressing Neurons

    PubMed Central

    Molet, Jenny; Gunn, Benjamin G.; Ressler, Kerry

    2015-01-01

    Transgenic mice, including lines targeting corticotropin-releasing factor (CRF or CRH), have been extensively employed to study stress neurobiology. These powerful tools are poised to revolutionize our understanding of the localization and connectivity of CRH-expressing neurons, and the crucial roles of CRH in normal and pathological conditions. Accurate interpretation of studies using cell type-specific transgenic mice vitally depends on congruence between expression of the endogenous peptide and reporter. If reporter expression does not faithfully reproduce native gene expression, then effects of manipulating unintentionally targeted cells may be misattributed. Here, we studied CRH and reporter expression patterns in 3 adult transgenic mice: Crh-IRES-Cre;Ai14 (tdTomato mouse), Crfp3.0CreGFP, and Crh-GFP BAC. We employed the CRH antiserum generated by Vale after validating its specificity using CRH-null mice. We focused the analyses on stress-salient regions, including hypothalamus, amygdala, bed nucleus of the stria terminalis, and hippocampus. Expression patterns of endogenous CRH were consistent among wild-type and transgenic mice. In tdTomato mice, most CRH-expressing neurons coexpressed the reporter, yet the reporter identified a few non-CRH-expressing pyramidal-like cells in hippocampal CA1 and CA3. In Crfp3.0CreGFP mice, coexpression of CRH and the reporter was found in central amygdala and, less commonly, in other evaluated regions. In Crh-GFP BAC mice, the large majority of neurons expressed either CRH or reporter, with little overlap. These data highlight significant diversity in concordant expression of reporter and endogenous CRH among 3 available transgenic mice. These findings should be instrumental in interpreting important scientific findings emerging from the use of these potent neurobiological tools. PMID:26402844

  11. Expression patterns of conserved microRNAs in the male gametophyte of loblolly pine (Pinus taeda).

    PubMed

    Quinn, Christina R; Iriyama, Rie; Fernando, Danilo D

    2014-06-01

    MicroRNAs (miRNAs) are small RNAs that regulate genes involved in various aspects of plant development, but their presence and expression patterns in the male gametophytes of gymnosperms have not yet been established. Therefore, this study identified and compared the expression patterns of conserved miRNAs from two stages of the male gametophyte of loblolly pine (Pinus taeda), which are the mature (ungerminated) and germinated pollen. Microarray was used to identify conserved miRNAs that varied in expression between these two stages of the loblolly pine male gametophyte. Forty-seven conserved miRNAs showed significantly different expression levels between mature and germinated loblolly pine pollen. In particular, miRNAs representing 14 and 8 families were up- and down-regulated in germinated loblolly pine pollen, respectively. qRT-PCR was used to validate their expression patterns using representative miRNAs. Target genes and proteins were identified using psRNATarget program. Predicted targets of the 22 miRNA families belong mostly to classes of genes involved in defense/stress response, metabolism, regulation, and signaling. qRT-PCR was also used to validate the expression patterns of representative target genes. This study shows that conserved miRNAs are expressed in mature and germinated loblolly pine pollen. Many of these miRNAs are differentially expressed, which indicates that the two stages of the male gametophyte examined are regulated at the miRNA level. This study also expands our knowledge of the male gametophytes of seed plants by providing insights on some similarities and differences in the types and expression patterns of conserved miRNAs between loblolly pine with those of rice and Arabidopsis.

  12. Microarray-Based Comparisons of Ion Channel Expression Patterns: Human Keratinocytes to Reprogrammed hiPSCs to Differentiated Neuronal and Cardiac Progeny

    PubMed Central

    Stockmann, Marianne; Lin, Qiong; Lechel, André; Proepper, Christian; Boeckers, Tobias M.; Kleger, Alexander

    2013-01-01

    Ion channels are involved in a large variety of cellular processes including stem cell differentiation. Numerous families of ion channels are present in the organism which can be distinguished by means of, for example, ion selectivity, gating mechanism, composition, or cell biological function. To characterize the distinct expression of this group of ion channels we have compared the mRNA expression levels of ion channel genes between human keratinocyte-derived induced pluripotent stem cells (hiPSCs) and their somatic cell source, keratinocytes from plucked human hair. This comparison revealed that 26% of the analyzed probes showed an upregulation of ion channels in hiPSCs while just 6% were downregulated. Additionally, iPSCs express a much higher number of ion channels compared to keratinocytes. Further, to narrow down specificity of ion channel expression in iPS cells we compared their expression patterns with differentiated progeny, namely, neurons and cardiomyocytes derived from iPS cells. To conclude, hiPSCs exhibit a very considerable and diverse ion channel expression pattern. Their detailed analysis could give an insight into their contribution to many cellular processes and even disease mechanisms. PMID:23690787

  13. Olfactory and amygdalar structures of the chicken ventral pallium based on the combinatorial expression patterns of LIM and other developmental regulatory genes.

    PubMed

    Abellán, Antonio; Legaz, Isabel; Vernier, Baptiste; Rétaux, Sylvie; Medina, Loreta

    2009-09-20

    We compared the combinatorial expression patterns of several LIM domain-containing regulatory genes in the ventrolateral pallium of mouse and chicken, in order to identify the homologues of the ventral pallial amygdala and other olfactory structures in birds. Lmo3, Lmo4, Lhx2, and Lhx9 showed comparable expression patterns in the telencephalon of mouse and chicken, which allowed distinction of the ventrolateral pallium and, particularly, the ventral pallial amygdala and entorhinal cortex. Lmo3 was expressed in most of the ventrolateral pallium in both species, including, in chicken, the piriform cortex and dorsal ventricular ridge (mesopallium, nidopallium, and arcopallium) and, in mouse, the piriform cortex, most of the claustral complex, and the pallial amygdala. Lhx9 was differentially expressed in the ventral pallium, where it was restricted to its rostral (olfactory bulb) and caudal (amygdalar and entorhinal) poles. In the caudal pole, expression of Lhx9 overlapped that of its paralog Lhx2. According to these expression patterns, the chicken ventral pallial amygdala appears to include the caudal dorsolateral pallium, the caudal nidopallium, and the whole arcopallium, and each one relates to a distinct ventricular sector. Finally, the combinatorial expression patterns of Lmo3, Lhx9, and Lmo4 distinguished four distinct subdivisions in the superficial, olfactorecipient area of the chicken ventral pallium, which appear comparable to the piriform, entorhinal, amygdalopiriform, and amygdalar cortices of mammals. The results are discussed in the context of the two existing, opposite views on the homology of the dorsal ventricular ridge of sauropsids and in terms of the evolution of pallial derivatives.

  14. Spatial Analysis of Expression Patterns Predicts Genetic Interactions at the Mid-Hindbrain Boundary

    PubMed Central

    Wittmann, Dominik M.; Blöchl, Florian; Trümbach, Dietrich; Wurst, Wolfgang; Prakash, Nilima; Theis, Fabian J.

    2009-01-01

    The isthmic organizer mediating differentiation of mid- and hindbrain during vertebrate development is characterized by a well-defined pattern of locally restricted gene expression domains around the mid-hindbrain boundary (MHB). This pattern is established and maintained by a regulatory network between several transcription and secreted factors that is not yet understood in full detail. In this contribution we show that a Boolean analysis of the characteristic spatial gene expression patterns at the murine MHB reveals key regulatory interactions in this network. Our analysis employs techniques from computational logic for the minimization of Boolean functions. This approach allows us to predict also the interplay of the various regulatory interactions. In particular, we predict a maintaining, rather than inducing, effect of Fgf8 on Wnt1 expression, an issue that remained unclear from published data. Using mouse anterior neural plate/tube explant cultures, we provide experimental evidence that Fgf8 in fact only maintains but does not induce ectopic Wnt1 expression in these explants. In combination with previously validated interactions, this finding allows for the construction of a regulatory network between key transcription and secreted factors at the MHB. Analyses of Boolean, differential equation and reaction-diffusion models of this network confirm that it is indeed able to explain the stable maintenance of the MHB as well as time-courses of expression patterns both under wild-type and various knock-out conditions. In conclusion, we demonstrate that similar to temporal also spatial expression patterns can be used to gain information about the structure of regulatory networks. We show, in particular, that the spatial gene expression patterns around the MHB help us to understand the maintenance of this boundary on a systems level. PMID:19936059

  15. Clustering change patterns using Fourier transformation with time-course gene expression data.

    PubMed

    Kim, Jaehee

    2011-01-01

    To understand the behavior of genes, it is important to explore how the patterns of gene expression change over a period of time because biologically related gene groups can share the same change patterns. In this study, the problem of finding similar change patterns is induced to clustering with the derivative Fourier coefficients. This work is aimed at discovering gene groups with similar change patterns which share similar biological properties. We developed a statistical model using derivative Fourier coefficients to identify similar change patterns of gene expression. We used a model-based method to cluster the Fourier series estimation of derivatives. We applied our model to cluster change patterns of yeast cell cycle microarray expression data with alpha-factor synchronization. It showed that, as the method clusters with the probability-neighboring data, the model-based clustering with our proposed model yielded biologically interpretable results. We expect that our proposed Fourier analysis with suitably chosen smoothing parameters could serve as a useful tool in classifying genes and interpreting possible biological change patterns.

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

    PubMed

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

    2017-10-04

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

  17. Sequence evolution and sex-specific expression patterns of the C class floral identity gene, SpAGAMOUS, in dioecious Spinacia oleracea L.

    PubMed

    Sather, D Noah; York, Amber; Pobursky, Kevin J; Golenberg, Edward M

    2005-10-01

    Development in dioecious cultivated spinach, Spinacia oleracea, is distinguished by the absence of alternative reproductive organ primordia in male and female flowers. Given the highly derived floral developmental program in spinach, we wished to characterize a spinach C class floral identity gene and to determine the patterns of sequence evolution as well as compare the spatial and temporal expression patterns with those of AGAMOUS. The isolated cDNA sequence clusters phylogenetically within the AGAMOUS/FARINELLI C class clade. In comparison with the SLM1 sequence from the related Silene latifolia, amino acid replacements are highly conservative and non-randomly distributed, being predominantly found in hinge regions or on exposed surfaces of helices. The spinach gene (SpAGAMOUS) appears to be exclusively expressed in reproductive tissues and not in vegetative organs. Initial expression of SpAGAMOUS is similar in male and female floral primordia. However, upon initiation of the first whorl organs, SpAGAMOUS becomes restricted to meristemic regions from which the reproductive primordia will develop. This results in an early gender-specific pattern. Thus, the spinach C class gene is differentially expressed prior to reproductive organ development and is, at least, correlated with, if not directly involved in, the sexual dimorphism in spinach.

  18. EPIG-Seq: extracting patterns and identifying co-expressed genes from RNA-Seq data.

    PubMed

    Li, Jianying; Bushel, Pierre R

    2016-03-22

    RNA sequencing (RNA-Seq) measures genome-wide gene expression. RNA-Seq data is count-based rendering normal distribution models for analysis inappropriate. Normalization of RNA-Seq data to transform the data has limitations which can adversely impact the analysis. Furthermore, there are a few count-based methods for analysis of RNA-Seq data but they are essentially for pairwise analysis of treatment groups or multiclasses but not pattern-based to identify co-expressed genes. We adapted our extracting patterns and identifying genes methodology for RNA-Seq (EPIG-Seq) count data. The software uses count-based correlation to measure similarity between genes, quasi-Poisson modelling to estimate dispersion in the data and a location parameter to indicate magnitude of differential expression. EPIG-Seq is different than any other software currently available for pattern analysis of RNA-Seq data in that EPIG-Seq 1) uses count level data and supports cases of inflated zeros, 2) identifies statistically significant clusters of genes that are co-expressed across experimental conditions, 3) takes into account dispersion in the replicate data and 4) provides reliable results even with small sample sizes. EPIG-Seq operates in two steps: 1) extract the pattern profiles from data as seeds for clustering co-expressed genes and 2) cluster the genes to the pattern seeds and compute statistical significance of the pattern of co-expressed genes. EPIG-Seq provides a table of the genes with bootstrapped p-values and profile plots of the patterns of co-expressed genes. In addition, EPIG-Seq provides a heat map and principal component dimension reduction plot of the clustered genes as visual aids. We demonstrate the utility of EPIG-Seq through the analysis of toxicogenomics and cancer data sets to identify biologically relevant co-expressed genes. EPIG-Seq is available at: sourceforge.net/projects/epig-seq. EPIG-Seq is unlike any other software currently available for pattern analysis of

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

    PubMed

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

    2011-11-01

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

  20. Ordered expression pattern of Hox and ParaHox genes along the alimentary canal in the ascidian juvenile.

    PubMed

    Nakayama, Satoshi; Satou, Kunihiro; Orito, Wataru; Ogasawara, Michio

    2016-07-01

    The Hox and ParaHox genes of bilateria share a similar expression pattern along the body axis and are known to be associated with anterior-posterior patterning. In vertebrates, the Hox genes are also expressed in presomitic mesoderm and gut endoderm and the ParaHox genes show a restricted expression pattern in the gut-related derivatives. Regional expression patterns in the embryonic central nervous system of the basal chordates amphioxus and ascidian have been reported; however, little is known about their endodermal expression in the alimentary canal. We focus on the Hox and ParaHox genes in the ascidian Ciona intestinalis and investigate the gene expression patterns in the juvenile, which shows morphological regionality in the alimentary canal. Gene expression analyses by using whole-mount in situ hybridization reveal that all Hox genes have a regional expression pattern along the alimentary canal. Expression of Hox1 to Hox4 is restricted to the posterior region of pharyngeal derivatives. Hox5 to Hox13 show an ordered expression pattern correlated with each Hox gene number along the postpharyngeal digestive tract. This expression pattern along the anterior-posterior axis has also been observed in Ciona ParaHox genes. Our observations suggest that ascidian Hox and ParaHox clusters are dispersed; however, the ordered expression patterns along the alimentary canal appear to be conserved among chordates.

  1. Gene Expression Profiles in Peripheral Blood Mononuclear Cells Can Distinguish Patients with Non-Small-Cell Lung Cancer from Patients with Non-Malignant Lung Disease

    PubMed Central

    Showe, Michael K.; Vachani, Anil; Kossenkov, Andrew V.; Yousef, Malik; Nichols, Calen; Nikonova, Elena V.; Chang, Celia; Kucharczuk, John; Tran, Bao; Wakeam, Elliot; Yie, Ting An; Speicher, David; Rom, William N.; Albelda, Steven

    2009-01-01

    Early diagnosis of lung cancer followed by surgery presently is the most effective treatment for non-small-cell lung cancer (NSCLC). An accurate, minimally invasive test that could detect early disease would permit timely intervention and potentially reduce mortality. Recent studies have shown that the peripheral blood can carry information related to the presence of disease, including prognostic information and information on therapeutic response. We have analyzed gene expression in peripheral blood mononuclear cell (PBMC) samples including 137 patients with NSCLC tumors and 91 patient controls with non-malignant lung conditions, including histologically diagnosed benign nodules. Subjects were primarily smokers and former smokers. We have identified a 29-gene signature that separates these two patient classes with 86% accuracy (91% sensitivity, 80% specificity). Accuracy in an independent validation set, including samples from a new location, was 78% (sensitivity of 76% and specificity of 82%). An analysis of this NSCLC-gene signature in 18 NSCLCs taken pre-surgery, with matched samples from 2-5 months post-surgery, showed that in 78% of cases, the signature was reduced post-surgery and disappeared entirely in 33%. Our results demonstrate the feasibility of using peripheral blood gene expression signatures to identify early-stage NSCLC in at-risk populations. PMID:19951989

  2. Genome-wide measurement of spatial expression in patterning mutants of Drosophila melanogaster

    PubMed Central

    Combs, Peter A.; Eisen, Michael B.

    2017-01-01

    Patterning in the Drosophila melanogaster embryo is affected by multiple maternal factors, but the effect of these factors on spatial gene expression has not been systematically analyzed. Here we characterize the effect of the maternal factors Zelda, Hunchback and Bicoid by cryosectioning wildtype and mutant blastoderm stage embryos and sequencing mRNA from each slice. The resulting atlas of spatial gene expression highlights the intersecting roles of these factors in regulating spatial patterns, and serves as a resource for researchers studying spatial patterning in the early embryo. We identify a large number of genes with both expected and unexpected patterning changes, and through integrated analysis of transcription factor binding data identify common themes in genes with complex dependence on these transcription factors. PMID:28299188

  3. Comparison of the patterns of milk ejection during repeated breast expression sessions in women.

    PubMed

    Prime, Danielle K; Geddes, Donna T; Hepworth, Anna R; Trengove, Naomi J; Hartmann, Peter E

    2011-08-01

    This study aimed to investigate the consistency of milk ejections and milk expression characteristics within mothers at repeated expression sessions. Twenty-five breastfeeding mothers expressed their breasts simultaneously on three occasions within 3 weeks, and follow-up visits were performed at 6, 9, and 12 months of lactation. During the 15-minute expression, milk was collected onto a continuous weigh balance to measure milk flow rate. The number of milk ejections was similar at the three sessions (5.1±2.0), decreasing at the 12-month follow-up (3.3±1.2). Mothers had a similar pattern of milk ejection at each session. The time that each milk ejection occurred was consistent for the first 9 months of lactation. Of the four milk ejection patterns identified, each removed a similar percentage of available milk but varied in the time to reach 80% of the total expression volume. The first two milk ejections produced the greatest percentage (62%) of total milk volume during breast expression. For each individual mother, the timing, pattern, and number of milk ejections were consistent, suggesting a predetermined release of oxytocin. In light of the innate oxytocin release and milk removal characteristics in women, there is potential for individual tailoring of the duration of expression.

  4. Lactase gene promoter fragments mediate differential spatial and temporal expression patterns in transgenic mice.

    PubMed

    Wang, Zhi; Maravelias, Charalambos; Sibley, Eric

    2006-04-01

    Lactase gene expression is spatiotemporally regulated during mammalian gut development. We hypothesize that distinct DNA control regions specify appropriate spatial and temporal patterning of lactase gene expression. In order to define regions of the lactase promoter involved in mediating intestine-specific and spatiotemporal restricted expression, transgenic mice harboring 100 bp, 1.3- and 2.0- kb fragments of the 5' flanking region of the rat lactase gene cloned upstream of a luciferase reporter were characterized. The 100-bp lactase promoter-reporter transgenic mouse line expressed maximal luciferase activity in the intestine with a posterior shift in spatial restriction and ectopic expression in the stomach and lung. The temporal pattern of expression mediated by the 1.3-kb promoter?reporter transgene increases with postnatal maturation in contrast with the postnatal decline mediated by the 2.0-kb promoter-reporter transgene and the endogenous lactase gene. The differential transgene expression patterns mediated by the lactase promoter fragments suggests that intestine-specific spatial and temporal control elements reside in distinct regions of the DNA sequences upstream of the lactase gene transcription start-site.

  5. Spatial Patterns of Alkaline Phosphatase Expression within Bacterial Colonies and Biofilms in Response to Phosphate Starvation

    PubMed Central

    Huang, Ching-Tsan; Xu, Karen D.; McFeters, Gordon A.; Stewart, Philip S.

    1998-01-01

    The expression of alkaline phosphatase in response to phosphate starvation was shown to be spatially and temporally heterogeneous in bacterial biofilms and colonies. A commercial alkaline phosphatase substrate that generates a fluorescent, insoluble product was used in conjunction with frozen sectioning techniques to visualize spatial patterns of enzyme expression in both Klebsiella pneumoniae and Pseudomonas aeruginosa biofilms. Some of the expression patterns observed revealed alkaline phosphatase activity at the boundary of the biofilm opposite the place where the staining substrate was delivered, indicating that the enzyme substrate penetrated the biofilm fully. Alkaline phosphatase accumulated linearly with time in K. pneumoniae colonies transferred from high-phosphate medium to low-phosphate medium up to specific activities of 50 μmol per min per mg of protein after 24 h. In K. pneumoniae biofilms and colonies, alkaline phosphatase was initially expressed in the region of the biofilm immediately adjacent to the carbon and energy source (glucose). In time, the region of alkaline phosphatase expression expanded inward until it spanned most, but not all, of the biofilm or colony depth. In contrast, expression of alkaline phosphatase in P. aeruginosa biofilms occurred in a thin, sharply delineated band at the biofilm-bulk fluid interface. In this case, the band of activity never occupied more than approximately one-sixth of the biofilm. These results are consistent with the working hypothesis that alkaline phosphatase expression patterns are primarily controlled by the local availability of either the carbon and energy source or the electron acceptor. PMID:9546188

  6. Developmental expression patterns of cuticular protein genes with the R&R Consensus from Anopheles gambiae

    PubMed Central

    Togawa, Toru; Dunn, W. Augustine; Emmons, Aaron C.; Nagao, John; Willis, Judith H.

    2008-01-01

    CPR proteins are the largest cuticular protein family in arthropods. The whole genome sequence of Anopheles gambiae revealed 156 genes that code for proteins with the R&R Consensus and named CPRs. This protein family can be divided into RR-1 and RR-2 subgroups, postulated to contribute to different regions of the cuticle. We determined the temporal expression patterns of these genes throughout post-embryonic development by means of real-time qRT-PCR. Based on expression profiles, these genes were grouped into 21 clusters. Most of the genes were expressed with sharp peaks at single or multiple periods associated with molting. Genes coding for RR-1 and RR-2 proteins were found together in several co-expression clusters. Twenty-five genes were expressed exclusively at one metamorphic stage. Five out of six X-linked genes showed equal expression in males and females, supporting the presence of a gene dosage compensation system in An. gambiae. Many RR-2 genes are organized into sequence clusters whose members are extremely similar to each other and generally closely associated on a chromosome. Most genes in each sequence cluster are expressed with the same temporal expression pattern and at the same level, suggesting a shared mechanism to regulate their expression. PMID:18405829

  7. Interactive Exploration of Microarray Gene Expression Patterns in a Reduced Dimensional Space

    PubMed Central

    Misra, Jatin; Schmitt, William; Hwang, Daehee; Hsiao, Li-Li; Gullans, Steve; Stephanopoulos, George; Stephanopoulos, Gregory

    2002-01-01

    The very high dimensional space of gene expression measurements obtained by DNA microarrays impedes the detection of underlying patterns in gene expression data and the identification of discriminatory genes. In this paper we show the use of projection methods such as principal components analysis (PCA) to obtain a direct link between patterns in the genes and patterns in samples. This feature is useful in the initial interactive pattern exploration of gene expression data and data-driven learning of the nature and types of samples. Using oligonucleotide microarray measurements of 40 samples from different normal human tissues, we show that distinct patterns are obtained when the genes are projected on a two-dimensional plane spanned by the loadings of the two major principal components. These patterns define the particular genes associated with a sample class (i.e., tissue). When used separately from the other genes, these class-specific (i.e., tissue-specific) genes in turn define distinct tissue patterns in the projection space spanned by the scores of the two major principal components. In this study, PCA projection facilitated discriminatory gene selection for different tissues and identified tissue-specific gene expression signatures for liver, skeletal muscle, and brain samples. Furthermore, it allowed the classification of nine new samples belonging to these three types using the linear combination of the expression levels of the tissue-specific genes determined from the first set of samples. The application of the technique to other published data sets is also discussed. [Online supplementary material available at www.genome.org.] PMID:12097349

  8. Geometric Morphometrics on Gene Expression Patterns Within Phenotypes: A Case Example on Limb Development

    PubMed Central

    Martínez-Abadías, Neus; Mateu, Roger; Niksic, Martina; Russo, Lucia; Sharpe, James

    2016-01-01

    How the genotype translates into the phenotype through development is critical to fully understand the evolution of phenotypes. We propose a novel approach to directly assess how changes in gene expression patterns are associated with changes in morphology using the limb as a case example. Our method combines molecular biology techniques, such as whole-mount in situ hybridization, with image and shape analysis, extending the use of Geometric Morphometrics to the analysis of nonanatomical shapes, such as gene expression domains. Elliptical Fourier and Procrustes-based semilandmark analyses were used to analyze the variation and covariation patterns of the limb bud shape with the expression patterns of two relevant genes for limb morphogenesis, Hoxa11 and Hoxa13. We devised a multiple thresholding method to semiautomatically segment gene domains at several expression levels in large samples of limb buds from C57Bl6 mouse embryos between 10 and 12 postfertilization days. Besides providing an accurate phenotyping tool to quantify the spatiotemporal dynamics of gene expression patterns within developing structures, our morphometric analyses revealed high, non-random, and gene-specific variation undergoing canalization during limb development. Our results demonstrate that Hoxa11 and Hoxa13, despite being paralogs with analogous functions in limb patterning, show clearly distinct dynamic patterns, both in shape and size, and are associated differently with the limb bud shape. The correspondence between our results and already well-established molecular processes underlying limb development confirms that this morphometric approach is a powerful tool to extract features of development regulating morphogenesis. Such multilevel analyses are promising in systems where not so much molecular information is available and will advance our understanding of the genotype–phenotype map. In systematics, this knowledge will increase our ability to infer how evolution modified a common

  9. Inference of the Xenopus tropicalis embryonic regulatory network and spatial gene expression patterns

    PubMed Central

    2014-01-01

    Background During embryogenesis, signaling molecules produced by one cell population direct gene regulatory changes in neighboring cells and influence their developmental fates and spatial organization. One of the earliest events in the development of the vertebrate embryo is the establishment of three germ layers, consisting of the ectoderm, mesoderm and endoderm. Attempts to measure gene expression in vivo in different germ layers and cell types are typically complicated by the heterogeneity of cell types within biological samples (i.e., embryos), as the responses of individual cell types are intermingled into an aggregate observation of heterogeneous cell types. Here, we propose a novel method to elucidate gene regulatory circuits from these aggregate measurements in embryos of the frog Xenopus tropicalis using gene network inference algorithms and then test the ability of the inferred networks to predict spatial gene expression patterns. Results We use two inference models with different underlying assumptions that incorporate existing network information, an ODE model for steady-state data and a Markov model for time series data, and contrast the performance of the two models. We apply our method to both control and knockdown embryos at multiple time points to reconstruct the core mesoderm and endoderm regulatory circuits. Those inferred networks are then used in combination with known dorsal-ventral spatial expression patterns of a subset of genes to predict spatial expression patterns for other genes. Both models are able to predict spatial expression patterns for some of the core mesoderm and endoderm genes, but interestingly of different gene subsets, suggesting that neither model is sufficient to recapitulate all of the spatial patterns, yet they are complementary for the patterns that they do capture. Conclusion The presented methodology of gene network inference combined with spatial pattern prediction provides an additional layer of validation to

  10. Deep convolutional neural networks for annotating gene expression patterns in the mouse brain.

    PubMed

    Zeng, Tao; Li, Rongjian; Mukkamala, Ravi; Ye, Jieping; Ji, Shuiwang

    2015-05-07

    Profiling gene expression in brain structures at various spatial and temporal scales is essential to understanding how genes regulate the development of brain structures. The Allen Developing Mouse Brain Atlas provides high-resolution 3-D in situ hybridization (ISH) gene expression patterns in multiple developing stages of the mouse brain. Currently, the ISH images are annotated with anatomical terms manually. In this paper, we propose a computational approach to annotate gene expression pattern images in the mouse brain at various structural levels over the course of development. We applied deep convolutional neural network that was trained on a large set of natural images to extract features from the ISH images of developing mouse brain. As a baseline representation, we applied invariant image feature descriptors to capture local statistics from ISH images and used the bag-of-words approach to build image-level representations. Both types of features from multiple ISH image sections of the entire brain were then combined to build 3-D, brain-wide gene expression representations. We employed regularized learning methods for discriminating gene expression patterns in different brain structures. Results show that our approach of using convolutional model as feature extractors achieved superior performance in annotating gene expression patterns at multiple levels of brain structures throughout four developing ages. Overall, we achieved average AUC of 0.894 ± 0.014, as compared with 0.820 ± 0.046 yielded by the bag-of-words approach. Deep convolutional neural network model trained on natural image sets and applied to gene expression pattern annotation tasks yielded superior performance, demonstrating its transfer learning property is applicable to such biological image sets.

  11. F-Spondin/spon1b Expression Patterns in Developing and Adult Zebrafish

    PubMed Central

    Akle, Veronica; Guelin, Emmanuel; Yu, Lili; Brassard-Giordano, Helena; Slack, Barbara E.; Zhdanova, Irina V.

    2012-01-01

    F-spondin, an extracellular matrix protein, is an important player in embryonic morphogenesis and CNS development, but its presence and role later in life remains largely unknown. We generated a transgenic zebrafish in which GFP is expressed under the control of the F-spondin (spon1b) promoter, and used it in combination with complementary techniques to undertake a detailed characterization of the expression patterns of F-spondin in developing and adult brain and periphery. We found that F-spondin is often associated with structures forming long neuronal tracts, including retinal ganglion cells, the olfactory bulb, the habenula, and the nucleus of the medial longitudinal fasciculus (nMLF). F-spondin expression coincides with zones of adult neurogenesis and is abundant in CSF-contacting secretory neurons, especially those in the hypothalamus. Use of this new transgenic model also revealed F-spondin expression patterns in the peripheral CNS, notably in enteric neurons, and in peripheral tissues involved in active patterning or proliferation in adults, including the endoskeleton of zebrafish fins and the continuously regenerating pharyngeal teeth. Moreover, patterning of the regenerating caudal fin following fin amputation in adult zebrafish was associated with F-spondin expression in the blastema, a proliferative region critical for tissue reconstitution. Together, these findings suggest major roles for F-spondin in the CNS and periphery of the developing and adult vertebrate. PMID:22768035

  12. Gene expression pattern recognition algorithm inferences to classify samples exposed to chemical agents

    NASA Astrophysics Data System (ADS)

    Bushel, Pierre R.; Bennett, Lee; Hamadeh, Hisham; Green, James; Ableson, Alan; Misener, Steve; Paules, Richard; Afshari, Cynthia

    2002-06-01

    We present an analysis of pattern recognition procedures used to predict the classes of samples exposed to pharmacologic agents by comparing gene expression patterns from samples treated with two classes of compounds. Rat liver mRNA samples following exposure for 24 hours with phenobarbital or peroxisome proliferators were analyzed using a 1700 rat cDNA microarray platform. Sets of genes that were consistently differentially expressed in the rat liver samples following treatment were stored in the MicroArray Project System (MAPS) database. MAPS identified 238 genes in common that possessed a low probability (P < 0.01) of being randomly detected as differentially expressed at the 95% confidence level. Hierarchical cluster analysis on the 238 genes clustered specific gene expression profiles that separated samples based on exposure to a particular class of compound.

  13. Analysis of allelic expression patterns in clonal somatic cells by single-cell RNA-seq.

    PubMed

    Reinius, Björn; Mold, Jeff E; Ramsköld, Daniel; Deng, Qiaolin; Johnsson, Per; Michaëlsson, Jakob; Frisén, Jonas; Sandberg, Rickard

    2016-11-01

    Cellular heterogeneity can emerge from the expression of only one parental allele. However, it has remained controversial whether, or to what degree, random monoallelic expression of autosomal genes (aRME) is mitotically inherited (clonal) or stochastic (dynamic) in somatic cells, particularly in vivo. Here we used allele-sensitive single-cell RNA-seq on clonal primary mouse fibroblasts and freshly isolated human CD8(+) T cells to dissect clonal and dynamic monoallelic expression patterns. Dynamic aRME affected a considerable portion of the cells' transcriptomes, with levels dependent on the cells' transcriptional activity. Notably, clonal aRME was detected, but it was surprisingly scarce (<1% of genes) and mainly affected the most weakly expressed genes. Consequently, the overwhelming majority of aRME occurs transiently within individual cells, and patterns of aRME are thus primarily scattered throughout somatic cell populations rather than, as previously hypothesized, confined to patches of clonally related cells.

  14. MicroRNA Expression Analysis of Centenarians and Rheumatoid Arthritis Patients Reveals a Common Expression Pattern.

    PubMed

    Balzano, Francesca; Deiana, Marta; Dei Giudici, Silvia; Oggiano, Annalisa; Pasella, Sara; Pinna, Sara; Mannu, Andrea; Deiana, Nicola; Porcu, Baingio; Masala, Antonio G E; Pileri, Piera V; Scognamillo, Fabrizio; Pala, Carlo; Zinellu, Angelo; Carru, Ciriaco; Deiana, Luca

    2017-01-01

    Micro-RNA (miRNA) are a family of small non-coding ribonucleic acids that inhibits post-transcriptionally the expression of their target messenger RNA (mRNA). We are interested in studying the involvement of miRNA in longevity and autoimmune diseases. In this study we compared the different expression of seven microRNAs between human plasma healthy controls, plasma samples of centenarians and samples from patients with rheumatoid arthritis. We used the Life Technologies' protocol to quantify seven miRNAs from 62 plasma samples: 20 healthy human controls, 14 centenarians, 28 patients with rheumatoid arthritis. TaqMan MicroRNA assays were used to analyze the expression profiles of miR-125b-5p, miR-425-5p, miR-200b5p, miR-200c-3p, miR-579-3p, miR-212-3p, miR-21-5p and miR-126-3p. The relative expression of mature miRNAs was analyzed using software REST. Our results show that miR-425-5p, miR-21 and miR-212 significantly decreased in centenarians and in patients with rheumatoid arthritis compared with controls. Furthermore in this work we highlight a connection between corticosteroid treatment and miRNAs expression.

  15. Gene Transcript Abundance Profiles Distinguish Kawasaki Disease from Adenovirus Infection

    PubMed Central

    Popper, Stephen J.; Watson, Virginia E.; Shimizu, Chisato; Kanegaye, John T.; Burns, Jane C.; Relman, David A.

    2010-01-01

    Background Acute Kawasaki disease (KD) is difficult to distinguish from other illnesses that involve acute rash or fever, in part because the etiologic agent(s) and pathophysiology remain poorly characterized. As a result, diagnosis and critical therapies may be delayed. Methods We used DNA microarrays to identify possible diagnostic features of KD. We compared gene expression patterns in the blood of 23 children with acute KD and 18 age-matched febrile children with 3 illnesses that resemble KD. Results Genes associated with platelet and neutrophil activation were expressed at higher levels in patients with KD than in patients with acute adenovirus infections or systemic adverse drug reactions, but levels in patients with KD were not higher than those in patients with scarlet fever. Genes associated with B cell activation were also expressed at higher levels in patients with KD than in control subjects. A striking absence of interferon-stimulated gene expression in patients with KD was confirmed in an independent cohort of patients with KD. Using a set of 38 gene transcripts, we successfully predicted the diagnosis for 21 of 23 patients with KD and 7 of 8 patients with adenovirus infection. Conclusions These findings provide insight into the molecular features that distinguish KD from other febrile illnesses and support the feasibility of developing novel diagnostic reagents for KD based on the host response. PMID:19583510

  16. Hox and ParaHox gene expression in early body plan patterning of polyplacophoran mollusks

    PubMed Central

    Fritsch, Martin; Wollesen, Tim

    2016-01-01

    ABSTRACT Molecular developmental studies of various bilaterians have shown that the identity of the anteroposterior body axis is controlled by Hox and ParaHox genes. Detailed Hox and ParaHox gene expression data are available for conchiferan mollusks, such as gastropods (snails and slugs) and cephalopods (squids and octopuses), whereas information on the putative conchiferan sister group, Aculifera, is still scarce (but see Fritsch et al., 2015 on Hox gene expression in the polyplacophoran Acanthochitona crinita). In contrast to gastropods and cephalopods, the Hox genes in polyplacophorans are expressed in an anteroposterior sequence similar to the condition in annelids and other bilaterians. Here, we present the expression patterns of the Hox genes Lox5, Lox4, and Lox2, together with the ParaHox gene caudal (Cdx) in the polyplacophoran A. crinita. To localize Hox and ParaHox gene transcription products, we also investigated the expression patterns of the genes FMRF and Elav, and the development of the nervous system. Similar to the other Hox genes, all three Acr‐Lox genes are expressed in an anteroposterior sequence. Transcripts of Acr‐Cdx are seemingly present in the forming hindgut at the posterior end. The expression patterns of both the central class Acr‐Lox genes and the Acr‐Cdx gene are strikingly similar to those in annelids and nemerteans. In Polyplacophora, the expression patterns of the Hox and ParaHox genes seem to be evolutionarily highly conserved, while in conchiferan mollusks these genes are co‐opted into novel functions that might have led to evolutionary novelties, at least in gastropods and cephalopods. PMID:27098677

  17. Hox and ParaHox gene expression in early body plan patterning of polyplacophoran mollusks.

    PubMed

    Fritsch, Martin; Wollesen, Tim; Wanninger, Andreas

    2016-03-01

    Molecular developmental studies of various bilaterians have shown that the identity of the anteroposterior body axis is controlled by Hox and ParaHox genes. Detailed Hox and ParaHox gene expression data are available for conchiferan mollusks, such as gastropods (snails and slugs) and cephalopods (squids and octopuses), whereas information on the putative conchiferan sister group, Aculifera, is still scarce (but see Fritsch et al., 2015 on Hox gene expression in the polyplacophoran Acanthochitona crinita). In contrast to gastropods and cephalopods, the Hox genes in polyplacophorans are expressed in an anteroposterior sequence similar to the condition in annelids and other bilaterians. Here, we present the expression patterns of the Hox genes Lox5, Lox4, and Lox2, together with the ParaHox gene caudal (Cdx) in the polyplacophoran A. crinita. To localize Hox and ParaHox gene transcription products, we also investigated the expression patterns of the genes FMRF and Elav, and the development of the nervous system. Similar to the other Hox genes, all three Acr-Lox genes are expressed in an anteroposterior sequence. Transcripts of Acr-Cdx are seemingly present in the forming hindgut at the posterior end. The expression patterns of both the central class Acr-Lox genes and the Acr-Cdx gene are strikingly similar to those in annelids and nemerteans. In Polyplacophora, the expression patterns of the Hox and ParaHox genes seem to be evolutionarily highly conserved, while in conchiferan mollusks these genes are co-opted into novel functions that might have led to evolutionary novelties, at least in gastropods and cephalopods.

  18. Gene expression pattern of glucose transporters in the skeletal muscles of newly hatched chicks.

    PubMed

    Shimamoto, Saki; Ijiri, Daichi; Kawaguchi, Mana; Nakashima, Kazuki; Ohtsuka, Akira

    2016-07-01

    The gene expression pattern of the glucose transporters (GLUT1, GLUT3, GLUT8, and GLUT12) among pectoralis major and minor, biceps femoris, and sartorius muscles from newly hatched chicks was examined. GLUT1 mRNA level was higher in pectoralis major muscle than in the other muscles. Phosphorylated AKT level was also high in the same muscle, suggesting a relationship between AKT and GLUT1 expression.

  19. Chromosomal patterns of gene expression from microarray data: methodology, validation and clinical relevance in gliomas

    PubMed Central

    Turkheimer, Federico E; Roncaroli, Federico; Hennuy, Benoit; Herens, Christian; Nguyen, Minh; Martin, Didier; Evrard, Annick; Bours, Vincent; Boniver, Jacques; Deprez, Manuel

    2006-01-01

    Background Expression microarrays represent a powerful technique for the simultaneous investigation of thousands of genes. The evidence that genes are not randomly distributed in the genome and that their coordinated expression depends on their position on chromosomes has highlighted the need for mathematical approaches to exploit this dependency for the analysis of expression data-sets. Results We have devised a novel mathematical technique (CHROMOWAVE) based on the Haar wavelet transform and applied it to a dataset obtained with the Affymetrix® HG-U133_Plus_2 array in 27 gliomas. CHROMOWAVE generated multi-chromosomal pattern featuring low expression in chromosomes 1p, 4, 9q, 13, 18, and 19q. This pattern was not only statistically robust but also clinically relevant as it was predictive of favourable outcome. This finding was replicated on a data-set independently acquired by another laboratory. FISH analysis indicated that monosomy 1p and 19q was a frequent feature of tumours displaying the CHROMOWAVE pattern but that allelic loss on chromosomes 4, 9q, 13 and 18 was much less common. Conclusion The ability to detect expression changes of spatially related genes and to map their position on chromosomes makes CHROMOWAVE a valuable screening method for the identification and display of regional gene expression changes of clinical relevance. In this study, FISH data showed that monosomy was frequently associated with diffuse low gene expression on chromosome 1p and 19q but not on chromosomes 4, 9q, 13 and 18. Comparative genomic hybridisation, allelic polymorphism analysis and methylation studies are in progress in order to identify the various mechanisms involved in this multi-chromosomal expression pattern. PMID:17140431

  20. Diverse miRNA spatial expression patterns suggest important roles in homeostasis and regeneration in planarians.

    PubMed

    González-Estévez, Cristina; Arseni, Varvara; Thambyrajah, Roshana S; Felix, Daniel A; Aboobaker, A Aziz

    2009-01-01

    miRNAs are an important class of non-protein coding small RNAs whose specific functions in animals are rapidly being elucidated. It is clear that miRNAs can play crucial roles in stem cell maintenance, cell fate determination and differentiation. We use planarians, which possess a large population of pluripotent somatic stem cells, as a powerful model system to study many aspects of stem cell biology and regeneration. In particular we wish to investigate the regulatory role miRNAs may have in planarian stem cell self renewal, proliferation and differentiation. Here, we characterized the differential spatial patterns of expression of miRNAs in whole and regenerating planarians by in situ hybridization to nascent miRNA transcripts. These miRNA expression patterns are the first which have been determined for a Lophotrocozoan animal. We have characterized the expression patterns of 42 miRNAs in adult planarians, constituting a complete range of tissue specific expression patterns. We also followed miRNA expression during planarian regeneration. The majority of planarian miRNAs were expressed either in areas where stem cells (neoblasts) are located and/or in the nervous system. Some miRNAs were definitively expressed in stem cells and dividing cells as confirmed by in situ hybridisation after irradiation. We also found miRNAs to be expressed in germ stem cells of the sexual strain. Together, these data suggest an important role for miRNAs in stem cell regulation and in neural cell differentiation in planarians.

  1. mRNA Blood Expression Patterns In New Onset Idiopathic Pediatric Epilepsy

    PubMed Central

    Greiner, Hansel M; Horn, Paul S; Holland, Katherine; Collins, James; Hershey, Andrew D; Glauser, Tracy A

    2012-01-01

    Purpose Determine if blood mRNA expression patterns in children with newly diagnosed untreated idiopathic epilepsy are different than those in healthy controls. Determine the differential expression patterns between epilepsy subjects with generalized onset or partial onset seizures compared to healthy controls. Methods Whole blood was obtained from otherwise healthy pediatric subjects with newly diagnosed untreated idiopathic epilepsy along with healthy pediatric controls. mRNA was isolated and hybridized to Affymetrix HGU 133 2.0+ microarrays. Analysis was performed using Genespring. Differentially expressed gene lists resulted from comparison of i) epilepsy and control groups and ii) seizure type subgroups with controls.. Tissue expression and gene ontology analysis was performed using DAVID. Key findings Thirty-seven epilepsy patients and 28 controls were included. Overall, 575 genes were differentially expressed in subjects with epilepsy compared to controls. The generalized seizure subgroup versus control (GvC) gene list and the partial seizure subgroup versus control (PvC) gene list were different (p < 0.05). Tissue expression analysis identified almost half of the genes in GvC and PvC as brain based. Functional group analysis identified several biologically relevant pathways. In GvC, these included mitochondria and lymphocyte activation. In PvC, apoptosis, inflammatory defense and cell motion pathways were identified. Significance A unique, biologically meaningful mRNA expression pattern is detectable in whole blood of pediatric subjects with new onset and untreated epilepsy. This analysis finds many similar pathways to those identified in brain studies examining lesional intractable epilepsy. Blood mRNA expression patterns show promise as a target for biomarker development in pediatric epilepsy. PMID:23167847

  2. Abundantly and rarely expressed Lhc protein genes exhibit distinct regulation patterns in plants.

    PubMed

    Klimmek, Frank; Sjödin, Andreas; Noutsos, Christos; Leister, Dario; Jansson, Stefan

    2006-03-01

    We have analyzed gene regulation of the Lhc supergene family in poplar (Populus spp.) and Arabidopsis (Arabidopsis thaliana) using digital expression profiling. Multivariate analysis of the tissue-specific, environmental, and developmental Lhc expression patterns in Arabidopsis and poplar was employed to characterize four rarely expressed Lhc genes, Lhca5, Lhca6, Lhcb7, and Lhcb4.3. Those genes have high expression levels under different conditions and in different tissues than the abundantly expressed Lhca1 to 4 and Lhcb1 to 6 genes that code for the 10 major types of higher plant light-harvesting proteins. However, in some of the datasets analyzed, the Lhcb4 and Lhcb6 genes as well as an Arabidopsis gene not present in poplar (Lhcb2.3) exhibited minor differences to the main cooperative Lhc gene expression pattern. The pattern of the rarely expressed Lhc genes was always found to be more similar to that of PsbS and the various light-harvesting-like genes, which might indicate distinct physiological functions for the rarely and abundantly expressed Lhc proteins. The previously undetected Lhcb7 gene encodes a novel plant Lhcb-type protein that possibly contains an additional, fourth, transmembrane N-terminal helix with a highly conserved motif. As the Lhcb4.3 gene seems to be present only in Eurosid species and as its regulation pattern varies significantly from that of Lhcb4.1 and Lhcb4.2, we conclude it to encode a distinct Lhc protein type, Lhcb8.

  3. The formulation of the control of an expression pattern in a gene network by propositional calculus.

    PubMed

    Nakayama, Hideki; Tanaka, Hiroto; Ushio, Toshimitsu

    2006-06-07

    In this study we model a gene network as a continuous-time switching network. In this model, each gene has a binary state which indicates if the gene expresses or not. We propose a method to control a sequence of expression patterns in the gene network model by adding another continuous-time switching network. By using propositional calculus, we will show that the control problem can be formulated as a mixed-integer linear programming problem with linear constraints.

  4. Systematic analysis of gene expression patterns associated with postmortem interval in human tissues.

    PubMed

    Zhu, Yizhang; Wang, Likun; Yin, Yuxin; Yang, Ence

    2017-07-14

    Postmortem mRNA degradation is considered to be the major concern in gene expression research utilizing human postmortem tissues. A key factor in this process is the postmortem interval (PMI), which is defined as the interval between death and sample collection. However, global patterns of postmortem mRNA degradation at individual gene levels across diverse human tissues remain largely unknown. In this study, we performed a systematic analysis of alteration of gene expression associated with PMI in human tissues. From the Genotype-Tissue Expression (GTEx) database, we evaluated gene expression levels of 2,016 high-quality postmortem samples from 316 donors of European descent, with PMI ranging from 1 to 27 hours. We found that PMI-related mRNA degradation is tissue-specific, gene-specific, and even genotype-dependent, thus drawing a more comprehensive picture of PMI-associated gene expression across diverse human tissues. Additionally, we also identified 266 differentially variable (DV) genes, such as DEFB4B and IFNG, whose expression is significantly dispersed between short PMI (S-PMI) and long PMI (L-PMI) groups. In summary, our analyses provide a comprehensive profile of PMI-associated gene expression, which will help interpret gene expression patterns in the evaluation of postmortem tissues.

  5. The expression patterns of gremlin 1 and noggin in normal adult and tumor tissues.

    PubMed

    Laurila, Riikka; Parkkila, Seppo; Isola, Jorma; Kallioniemi, Anne; Alarmo, Emma-Leena

    2013-01-01

    Gremlin 1 and noggin are inhibitors of bone morphogenetic protein (BMP) signaling. They are vital during early development but their role in adult tissues has remained largely unresolved. The BMP signaling pathway has also been implicated in tumorigenesis, however with emphasis on the role of the ligands and receptors. We performed a concurrent survey of gremlin 1 and noggin protein expression in multiple normal and cancer samples, using immunohistochemistry on tissue microarrays containing 96 samples from 34 different normal organs/tissue sites and 208 samples of 34 different tumor types. In majority of both normal and tumor samples, gremlin 1 and noggin expression was negative or weak. However, normal stomach and skin demonstrated distinct gremlin 1 and noggin expression indicating a role in adult tissues. Likewise, strong expression of both antagonists was detected in Leydig cells of testis. In the tumor panel, the expression patterns were more variable but elevated BMP antagonist expression was detected for the first time in few cases, such as glioblastoma, hepatocellular carcinoma and diffuse B-cell lymphoma for gremlin 1 and renal granular cell tumor and thyroid papillary carcinoma for noggin. Even though gremlin 1 and noggin were not widely expressed in adult tissues, in a subset of organs their expression pattern indicated a potential role in normal tissue homeostasis as well as in malignancies.

  6. The expression patterns of gremlin 1 and noggin in normal adult and tumor tissues

    PubMed Central

    Laurila, Riikka; Parkkila, Seppo; Isola, Jorma; Kallioniemi, Anne; Alarmo, Emma-Leena

    2013-01-01

    Gremlin 1 and noggin are inhibitors of bone morphogenetic protein (BMP) signaling. They are vital during early development but their role in adult tissues has remained largely unresolved. The BMP signaling pathway has also been implicated in tumorigenesis, however with emphasis on the role of the ligands and receptors. We performed a concurrent survey of gremlin 1 and noggin protein expression in multiple normal and cancer samples, using immunohistochemistry on tissue microarrays containing 96 samples from 34 different normal organs/tissue sites and 208 samples of 34 different tumor types. In majority of both normal and tumor samples, gremlin 1 and noggin expression was negative or weak. However, normal stomach and skin demonstrated distinct gremlin 1 and noggin expression indicating a role in adult tissues. Likewise, strong expression of both antagonists was detected in Leydig cells of testis. In the tumor panel, the expression patterns were more variable but elevated BMP antagonist expression was detected for the first time in few cases, such as glioblastoma, hepatocellular carcinoma and diffuse B-cell lymphoma for gremlin 1 and renal granular cell tumor and thyroid papillary carcinoma for noggin. Even though gremlin 1 and noggin were not widely expressed in adult tissues, in a subset of organs their expression pattern indicated a potential role in normal tissue homeostasis as well as in malignancies. PMID:23826422

  7. Systematic expression analysis of Hox genes at adulthood reveals novel patterns in the central nervous system.

    PubMed

    Hutlet, Bertrand; Theys, Nicolas; Coste, Cécile; Ahn, Marie-Thérèse; Doshishti-Agolli, Konstantin; Lizen, Benoît; Gofflot, Françoise

    2016-04-01

    Hox proteins are key regulators of animal development, providing positional identity and patterning information to cells along the rostrocaudal axis of the embryo. Although their embryonic expression and function are well characterized, their presence and biological importance in adulthood remains poorly investigated. We provide here the first detailed quantitative and neuroanatomical characterization of the expression of the 39 Hox genes in the adult mouse brain. Using RT-qPCR we determined the expression of 24 Hox genes mainly in the brainstem of the adult brain, with low expression of a few genes in the cerebellum and the forebrain. Using in situ hybridization (ISH) we have demonstrated that expression of Hox genes is maintained in territories derived from the early segmental Hox expression domains in the hindbrain. Indeed, we show that expression of genes belonging to paralogy groups PG2-8 is maintained in the hindbrain derivatives at adulthood. The spatial colinearity, which characterizes the early embryonic expression of Hox genes, is still observed in sequential antero-posterior boundaries of expression. Moreover, the main mossy and climbing fibres precerebellar nuclei express PG2-8 Hox genes according to their migration origins. Second, ISH confirms the presence of Hox gene transcripts in territories where they are not detected during development, suggesting neo-expression in these territories in adulthood. Within the forebrain, we have mapped Hoxb1, Hoxb3, Hoxb4, Hoxd3 and Hoxa5 expression in restricted areas of the sensory cerebral cortices as well as in specific thalamic relay nuclei. Our data thus suggest a requirement of Hox genes beyond their role of patterning genes, providing a new dimension to their functional relevance in the central nervous system.

  8. Shh and Pax6 have unconventional expression patterns in embryonic morphogenesis in Sepia officinalis (Cephalopoda).

    PubMed

    Navet, Sandra; Andouche, Aude; Baratte, Sébastien; Bonnaud, Laure

    2009-10-01

    Cephalopods show a very complex nervous system, particularly derived when compared to other molluscs. In vertebrates, the setting up of the nervous system depends on genes such as Shh and Pax6. In this paper we assess Shh and Pax6 expression patterns during Sepia officinalis development by whole-mount in situ hybridization. In vertebrates, Shh has been shown to indirectly inhibit Pax6. This seems to be the case in cephalopods as the expression patterns of these genes do not overlap during S. officinalis development. Pax6 is expressed in the optic region and brain and Shh in gut structures, as already seen in vertebrates and Drosophila. Thus, both genes show expression in analogous structures in vertebrates. Surprisingly, they also exhibit unconventional expressions such as in gills for Pax6 and ganglia borders for Shh. They are also expressed in many cephalopods' derived characters among molluscs as in arm suckers for Pax6 and beak producing tissues, nuchal organ and neural cord of the arms for Shh. This new data supports the fact that molecular control patterns have evolved with the appearance of morphological novelties in cephalopods as shown in this new model, S. officinalis.

  9. Coordinated patterns of gene expressions for adult muscle build-up in transgenic mice expressing myostatin propeptide.

    PubMed

    Zhao, Baoping; Li, Eileena J; Wall, Robert J; Yang, Jinzeng

    2009-07-08

    Skeletal muscle growth and maintenance are essential for human health. One of the muscle regulatory genes, namely myostatin, a member of transforming growth factor-beta, plays a dominant role in the genetic control of muscle mass. Myostatin is synthesized as a precursor protein, which generates the N-terminal propeptide and the C-terminal mature myostatin peptide by a post-translational cleavage event. Previously, transgenic over-expression of myostatin propeptide in skeletal muscle results in significant muscle growth in early stages of development. The objectives of present study were to further characterize muscle growth in later stages of life and to identify genes and their expression patterns that are responsible for adult muscle build-up by myostatin propeptide. Immunohistochemical staining with an antibody to the N-terminus indicates a high level of myostatin propeptide present in the muscles of transgenic mice while there were no apparent differences in myostatin protein distribution in the muscle fibers between the transgenic and wild-type mice. Main individual muscles increased by 76-152% in the transgenic mice over their wild-type littermate mice at 12 months of age. A large number of nuclei were localized in the central and basal lamina of the myofibers in the transgenic mice as the number of nuclei per fiber and 100 microm(2) area was significantly higher in transgenic mice than wild-type mice. By systemic comparisons of global mRNA expression patterns between transgenic mice and wild-type littermates using microarray and qRT-PCR techniques, we have identified distinct gene expression patterns to support adult muscle build-up by myostatin propeptide, which are comprised of enhanced expressions of myogenic regulatory factors and extracelullar matrix components, and differentially down-regulated expressions of genes related to protein degradation and mitochondrial ATP synthesis. The results present a coordinated pattern of gene expressions for reduced

  10. Coordinated patterns of gene expressions for adult muscle build-up in transgenic mice expressing myostatin propeptide

    PubMed Central

    Zhao, Baoping; Li, Eileena J; Wall, Robert J; Yang, Jinzeng

    2009-01-01

    Background Skeletal muscle growth and maintenance are essential for human health. One of the muscle regulatory genes, namely myostatin, a member of transforming growth factor-β, plays a dominant role in the genetic control of muscle mass. Myostatin is synthesized as a precursor protein, which generates the N-terminal propeptide and the C-terminal mature myostatin peptide by a post-translational cleavage event. Previously, transgenic over-expression of myostatin propeptide in skeletal muscle results in significant muscle growth in early stages of development. The objectives of present study were to further characterize muscle growth in later stages of life and to identify genes and their expression patterns that are responsible for adult muscle build-up by myostatin propeptide. Results Immunohistochemical staining with an antibody to the N-terminus indicates a high level of myostatin propeptide present in the muscles of transgenic mice while there were no apparent differences in myostatin protein distribution in the muscle fibers between the transgenic and wild-type mice. Main individual muscles increased by 76–152% in the transgenic mice over their wild-type littermate mice at 12 months of age. A large number of nuclei were localized in the central and basal lamina of the myofibers in the transgenic mice as the number of nuclei per fiber and 100 μm2 area was significantly higher in transgenic mice than wild-type mice. By systemic comparisons of global mRNA expression patterns between transgenic mice and wild-type littermates using microarray and qRT-PCR techniques, we have identified distinct gene expression patterns to support adult muscle build-up by myostatin propeptide, which are comprised of enhanced expressions of myogenic regulatory factors and extracelullar matrix components, and differentially down-regulated expressions of genes related to protein degradation and mitochondrial ATP synthesis. Conclusion The results present a coordinated pattern of gene

  11. Loss of nuclear expression of parafibromin distinguishes parathyroid carcinomas and hyperparathyroidism-jaw tumor (HPT-JT) syndrome-related adenomas from sporadic parathyroid adenomas and hyperplasias.

    PubMed

    Gill, Anthony J; Clarkson, Adele; Gimm, Oliver; Keil, Juliane; Dralle, Henning; Howell, Viive M; Marsh, Deborah J

    2006-09-01

    Parathyroid carcinoma is notoriously difficult to diagnose with confidence in borderline cases. Commonly there is a long lag time between diagnosis and clinical evidence of malignant behavior even in histopathologically straightforward lesions. There is therefore a need for a novel adjunctive marker to assist in the diagnosis of carcinoma. Parafibromin is the protein encoded by the putative tumor suppressor gene HRPT2. Mutations predicted to inactivate parafibromin were first detected in the germline of patients with hyperparathyroidism-jaw tumor (HPT-JT) syndrome. Subsequently, somatic mutations have been identified in the majority of sporadic carcinomas. We performed immunohistochemistry for parafibromin on 115 parathyroid tissues comprising 4 HPT-JT-related tumors (3 adenomas and 1 carcinoma), 11 sporadic parathyroid carcinomas, 79 sporadic adenomas, 3 multiple endocrine neoplasia 2A-related adenomas, 2 sporadic primary hyperplasias, 2 multiple endocrine neoplasia (MEN)-1-related hyperplasias, 6 secondary hyperplasias, 4 tertiary hyperplasias, and 4 normal parathyroid glands. There was complete absence of nuclear staining in 3 of 4 (75%) HPT-JT-related tumors and 8 of 11 (73%) sporadic parathyroid carcinomas and focal weak staining in 1 of 4 HPT-JT tumors and 2 of 11 sporadic parathyroid carcinomas. Only 1 parathyroid carcinoma exhibited diffuse strong nuclear expression of parafibromin. In contrast, 98 of 100 non-HPT-JT-related benign parathyroids showed diffuse strong nuclear positivity and 2 of 100 showed weak positive staining. We conclude that, in the correct clinical and pathologic context, complete absence of nuclear staining for parafibromin is diagnostic of parathyroid carcinoma or an HPT-JT-related tumor.

  12. Complexities of gene expression patterns in natural populations of an extremophile fish (Poecilia mexicana, Poeciliidae).

    PubMed

    Passow, Courtney N; Brown, Anthony P; Arias-Rodriguez, Lenin; Yee, Muh-Ching; Sockell, Alexandra; Schartl, Manfred; Warren, Wesley C; Bustamante, Carlos; Kelley, Joanna L; Tobler, Michael

    2017-08-01

    Variation in gene expression can provide insights into organismal responses to environmental stress and physiological mechanisms mediating adaptation to habitats with contrasting environmental conditions. We performed an RNA-sequencing experiment to quantify gene expression patterns in fish adapted to habitats with different combinations of environmental stressors, including the presence of toxic hydrogen sulphide (H2 S) and the absence of light in caves. We specifically asked how gene expression varies among populations living in different habitats, whether population differences were consistent among organs, and whether there is evidence for shared expression responses in populations exposed to the same stressors. We analysed organ-specific transcriptome-wide data from four ecotypes of Poecilia mexicana (nonsulphidic surface, sulphidic surface, nonsulphidic cave and sulphidic cave). The majority of variation in gene expression was correlated with organ type, and the presence of specific environmental stressors elicited unique expression differences among organs. Shared patterns of gene expression between populations exposed to the same environmental stressors increased with levels of organismal organization (from transcript to gene to physiological pathway). In addition, shared patterns of gene expression were more common between populations from sulphidic than populations from cave habitats, potentially indicating that physiochemical stressors with clear biochemical consequences can constrain the diversity of adaptive solutions that mitigate their adverse effects. Overall, our analyses provided insights into transcriptional variation in a unique system, in which adaptation to H2 S and darkness coincide. Functional annotations of differentially expressed genes provide a springboard for investigating physiological mechanisms putatively underlying adaptation to extreme environments. © 2017 John Wiley & Sons Ltd.

  13. CHARACTERIZATION OF THE EXPRESSION PATTERN OF ADRENERGIC RECEPTORS IN RAT TASTE BUDS

    PubMed Central

    ZHANG, Y.; KOLLI, T.; HIVLEY, R.; JABER, L.; ZHAO, F-l.; YAN, J.; HERNESS, S.

    2010-01-01

    Taste buds signal the presence of chemical stimuli in the oral cavity to the central nervous system using both early transduction mechanisms, which allow single cells to be depolarized via receptor-mediated signaling pathways, and late transduction mechanisms, which involve extensive cell-to-cell communication among the cells in the bud. The latter mechanisms, which involve a large number of neurotransmitters and neuropeptides, are less well understood. Among neurotransmitters, multiple lines of evidence suggest that norepinephrine plays a yet unknown role in the taste bud. This study investigated the expression pattern of adrenergic receptors in the rat posterior taste bud. Expression of α1A, α1B, α1D, α2A, α2B, α2C, β1, and the β2 adrenoceptor subtypes was observed in taste buds using RT-PCR and immunocytochemical techniques. Taste buds also expressed the biosynthetic enzyme for norepinephrine, dopamine β-hydroxylase (DβH), as well as the norepinephrine transporter. Further, expression of the epinephrine synthetic enzyme, phenylethanolamine N-methyltransferase (PNMT), was observed suggesting a possible role for this transmitter in the bud. Phenotyping adrenoceptor expression patterns with double labeling experiments to gustducin, synaptosomal-associated protein 25 (SNAP-25), and neural cell adhesion molecule (NCAM) suggests they are prominently expressed in subsets of cells known to express taste receptor molecules but segregated from cells known to have synapses with the afferent nerve fiber. Alpha and beta adrenoceptors co-express with one another in unique patterns as observed with immunocytochemistry and single cell RT-PCR. These data suggest that single cells express multiple adrenergic receptors and that adrenergic signaling may be particularly important in bitter, sweet, and umami taste qualities. In summary, adrenergic signaling in the taste bud occurs through complex pathways that include presynaptic and postsynaptic receptors and likely play

  14. Regulatory Divergence between Parental Alleles Determines Gene Expression Patterns in Hybrids

    PubMed Central

    Combes, Marie-Christine; Hueber, Yann; Dereeper, Alexis; Rialle, Stéphanie; Herrera, Juan-Carlos; Lashermes, Philippe

    2015-01-01

    Both hybridization and allopolyploidization generate novel phenotypes by conciliating divergent genomes and regulatory networks in the same cellular context. To understand the rewiring of gene expression in hybrids, the total expression of 21,025 genes and the allele-specific expression of over 11,000 genes were quantified in interspecific hybrids and their parental species, Coffea canephora and Coffea eugenioides using RNA-seq technology. Between parental species, cis- and trans-regulatory divergences affected around 32% and 35% of analyzed genes, respectively, with nearly 17% of them showing both. The relative importance of trans-regulatory divergences between both species could be related to their low genetic divergence and perennial habit. In hybrids, among divergently expressed genes between parental species and hybrids, 77% was expressed like one parent (expression level dominance), including 65% like C. eugenioides. Gene expression was shown to result from the expression of both alleles affected by intertwined parental trans-regulatory factors. A strong impact of C. eugenioides trans-regulatory factors on the upregulation of C. canephora alleles was revealed. The gene expression patterns appeared determined by complex combinations of cis- and trans-regulatory divergences. In particular, the observed biased expression level dominance seemed to be derived from the asymmetric effects of trans-regulatory parental factors on regulation of alleles. More generally, this study illustrates the effects of divergent trans-regulatory parental factors on the gene expression pattern in hybrids. The characteristics of the transcriptional response to hybridization appear to be determined by the compatibility of gene regulatory networks and therefore depend on genetic divergences between the parental species and their evolutionary history. PMID:25819221

  15. Regulatory divergence between parental alleles determines gene expression patterns in hybrids.

    PubMed

    Combes, Marie-Christine; Hueber, Yann; Dereeper, Alexis; Rialle, Stéphanie; Herrera, Juan-Carlos; Lashermes, Philippe

    2015-03-29

    Both hybridization and allopolyploidization generate novel phenotypes by conciliating divergent genomes and regulatory networks in the same cellular context. To understand the rewiring of gene expression in hybrids, the total expression of 21,025 genes and the allele-specific expression of over 11,000 genes were quantified in interspecific hybrids and their parental species, Coffea canephora and Coffea eugenioides using RNA-seq technology. Between parental species, cis- and trans-regulatory divergences affected around 32% and 35% of analyzed genes, respectively, with nearly 17% of them showing both. The relative importance of trans-regulatory divergences between both species could be related to their low genetic divergence and perennial habit. In hybrids, among divergently expressed genes between parental species and hybrids, 77% was expressed like one parent (expression level dominance), including 65% like C. eugenioides. Gene expression was shown to result from the expression of both alleles affected by intertwined parental trans-regulatory factors. A strong impact of C. eugenioides trans-regulatory factors on the upregulation of C. canephora alleles was revealed. The gene expression patterns appeared determined by complex combinations of cis- and trans-regulatory divergences. In particular, the observed biased expression level dominance seemed to be derived from the asymmetric effects of trans-regulatory parental factors on regulation of alleles. More generally, this study illustrates the effects of divergent trans-regulatory parental factors on the gene expression pattern in hybrids. The characteristics of the transcriptional response to hybridization appear to be determined by the compatibility of gene regulatory networks and therefore depend on genetic divergences between the parental species and their evolutionary history. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  16. DEVELOPMENT OF A 950-GENE DNA ARRAY FOR EXAMINING GENE EXPRESSION PATTERNS IN MOUSE TESTIS

    EPA Science Inventory

    Development of a 950-gene DNA array for examining gene expression patterns in mouse testis.

    Rockett JC, Christopher Luft J, Brian Garges J, Krawetz SA, Hughes MR, Hee Kirn K, Oudes AJ, Dix DJ.

    Reproductive Toxicology Division, National Health and Environmental Effec...

  17. GENE EXPRESSION PATTERNS OF CD-1 DAY-8 EMBRYO CULTURES EXPOSED TO BROMOCHLORO ACETIC ACID

    EPA Science Inventory

    Gene expression patterns of CD-1 day-8 embryo cultures exposed to bromochloro acetic acid

    Edward D. Karoly?*, Judith E. Schmid* and E. Sidney Hunter III*
    ?Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina and *Reproductiv...

  18. GENE EXPRESSION PATTERNS OF CD-1 DAY-8 EMBRYO CULTURES EXPOSED TO BROMOCHLORO ACETIC ACID

    EPA Science Inventory

    Gene expression patterns of CD-1 day-8 embryo cultures exposed to bromochloro acetic acid

    Edward D. Karoly?*, Judith E. Schmid* and E. Sidney Hunter III*
    ?Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina and *Reproductiv...

  19. Novel expression patterns of carotenoid pathway-related gene in citrus leaves and maturing fruits

    USDA-ARS?s Scientific Manuscript database

    Carotenoids are abundant in citrus fruits and vary among cultivars and species. In the present study, HPLC and real-time PCR were used to investigate the expression patterns of 23 carotenoid biosynthesis gene family members and their possible relation with carotenoid accumulation in flavedo, juice s...

  20. GENOMIC ORGANIZATION OF THE SP22 GENE AND A UNIQUE PATTERN OF EXPRESSION IN SPERMATOGENIC CELLS

    EPA Science Inventory

    GENOMIC ORGANIZATION OF THE SP22 GENE AND A UNIQUE PATTERN OF EXPRESSION IN SPERMATOGENIC CELLS.
    JE Welch*, RR Barbee*, JD Suarez*, NL Roberts*, and GR Klinefelter. Reproductive Toxicology Division, NHEERL, U.S. EPA, Research Triangle Park, NC, USA.
    Our laboratory has rep...

  1. GENOMIC ORGANIZATION OF THE SP22 GENE AND A UNIQUE PATTERN OF EXPRESSION IN SPERMATOGENIC CELLS

    EPA Science Inventory

    GENOMIC ORGANIZATION OF THE SP22 GENE AND A UNIQUE PATTERN OF EXPRESSION IN SPERMATOGENIC CELLS.
    JE Welch*, RR Barbee*, JD Suarez*, NL Roberts*, and GR Klinefelter. Reproductive Toxicology Division, NHEERL, U.S. EPA, Research Triangle Park, NC, USA.
    Our laboratory has rep...

  2. Mining and analysing spatio-temporal patterns of gene expression in an integrative database framework.

    PubMed

    Belmamoune, M; Potikanond, D; Verbeek, F J

    2010-03-25

    Mining patterns of gene expression provides a crucial approach in discovering knowledge such as finding genetic networks that underpin the embryonic development. Analysis of mining results and evaluation of their relevance in the domain remains a major concern. In this paper we describe our explorative studies in support of solutions to facilitate the analysis and interpretation of mining results. In our particular case we describe a solution that is found in the extension of the Gene Expression Management System (GEMS), i.e. an integrative framework for spatio-temporal organization of gene expression patterns of zebrafish to a framework supporting data mining, data analysis and patterns interpretation As a proof of principle, the GEMS has been equipped with data mining functionality suitable for spatio-temporal tracking, thereby generating added value to the submission of data for data mining and analysis. The analysis of the genetic networks is based on the availability of domain ontologies which dynamically provides meaning to the discovered patterns of gene expression data. Combination of data mining with the already presently available capabilities of GEMS will significantly augment current data processing and functional analysis strategies.

  3. Cytokeratin expression patterns as an indicator of tumour progression in oesophageal squamous cell carcinoma.

    PubMed

    Cintorino, M; Tripod, S A; Santopietro, R; Antonio, P; Lutfi, A; Chang, F; Syrjänen, S; Shen, Q; Tosi, P; Syrjänen, K

    2001-01-01

    Recent studies point out that cytokeratins (CKs) are involved in dynamic cell remodeling during cancer progression and particularly, CK expression patterns have been associated with invasion and metastasis. In oesophageal squamous cell cancer (ESCC), lymph node (LNN) metastasis is an important step in disease progression, invariably associated with an ominous prognosis. To assess whether specific CK expression patterns could represent reliable markers of tumor progression, a series of 111 ESCCs (59 lymph node-positive, 52-negative) derived from the high- incidence area of Linxian (Northern China), were subjected to immunohistochemical (IHC) analysis with an extensive panel of CK antibodies. Statistically significant differences were observed for CK18 (p=0.01), CK19 (p=0.04) and PKK1 (p=0.02) expression between the LNN-negative and LNN-positive ESCCs. Furthermore, significant correlation between specific CK distribution pattern and progressive disease (i.e., LNN metastasis) was evidenced. The results suggest that CK8, CK18 and CK19 expression and distribution pattern could be of predictive value as a marker of disease progression as defined by the appearance of lymph node metastases in oesophageal squamous cell cancer.

  4. A Database of microRNA Expression Patterns in Xenopus laevis

    PubMed Central

    Moxon, Simon; Lopez-Gomollon, Sara; Viaut, Camille; Tomlinson, Matthew L.; Patrushev, Ilya; Gilchrist, Michael J.; Dalmay, Tamas; Dotlic, Dario; Münsterberg, Andrea E.; Wheeler, Grant N.

    2015-01-01

    MicroRNAs (miRNAs) are short, non-coding RNAs around 22 nucleotides long. They inhibit gene expression either by translational repression or by causing the degradation of the mRNAs they bind to. Many are highly conserved amongst diverse organisms and have restricted spatio-temporal expression patterns during embryonic development where they are thought to be involved in generating accuracy of developmental timing and in supporting cell fate decisions and tissue identity. We determined the expression patterns of 180 miRNAs in Xenopus laevis embryos using LNA oligonucleotides. In addition we carried out small RNA-seq on different stages of early Xenopus development, identified 44 miRNAs belonging to 29 new families and characterized the expression of 5 of these. Our analyses identified miRNA expression in many organs of the developing embryo. In particular a large number were expressed in neural tissue and in the somites. Surprisingly none of the miRNAs we have looked at show expression in the heart. Our results have been made freely available as a resource in both XenMARK and Xenbase. PMID:26506012

  5. Dynamic patterns of expression for genes regulating cytokinin metabolism and signaling during rice inflorescence development.

    PubMed

    Yamburenko, Maria V; Kieber, Joseph J; Schaller, G Eric

    2017-01-01

    Inflorescence development in cereals, including such important crops as rice, maize, and wheat, directly affects grain number and size and is a key determinant of yield. Cytokinin regulates meristem size and activity and, as a result, has profound effects on inflorescence development and architecture. To clarify the role of cytokinin action in inflorescence development, we used the NanoString nCounter system to analyze gene expression in the early stages of rice panicle development, focusing on 67 genes involved in cytokinin biosynthesis, degradation, and signaling. Results point toward key members of these gene families involved in panicle development and indicate that the expression of many genes involved in cytokinin action differs between the panicle and vegetative tissues. Dynamic patterns of gene expression suggest that subnetworks mediate cytokinin action during different stages of panicle development. The variation of expression during panicle development is greater among genes encoding proteins involved in cytokinin metabolism and negative regulators of the pathway than for the genes in the primary response pathway. These results provide insight into the expression patterns of genes involved in cytokinin action during inflorescence development in a crop of agricultural importance, with relevance to similar processes in other monocots. The identification of subnetworks of genes expressed at different stages of early panicle development suggests that manipulation of their expression could have substantial effects on inflorescence architecture.

  6. Temporal and spatial expression pattern of Nnat during mouse eye development.

    PubMed

    Sel, Saadettin; Patzel, Eva; Poggi, Lucia; Kaiser, Delia; Kalinski, Thomas; Schicht, Martin; Paulsen, Friedrich; Nass, Norbert

    2017-01-01

    Neuronatin (Nnat) was initially identified as a highly expressed gene in neonatal mammalian brain. In this study, we analyze the spatial and temporal expression pattern of Nnat during mouse eye development as well as in the adult. The expression of Nnat was analyzed on mRNA as well as protein level. The presence of Nnat transcripts in the adult retina was examined using reverse transcription-polymerase chain reaction (RT-PCR). Nnat protein expression was evaluated by Western blot and immunohistochemistry during eye development at embryonic day (E) 12, 15, 16 and postnatal day (P) 7, 14, 30 and 175 (adult). Immunohistochemical studies of the developing mouse eye revealed Nnat expression in embryonic and adult neuroretina as well as in corneal epithelial, stromal, endothelial cells and in lens epithelium. Expression of Nnat was detected from E12 onwards and was also present in adult eyes. The expression pattern suggests that Nnat may play an important role during eye development and in the maintenance of mature eye. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Expression pattern of LINGO-1 in the developing nervous system of the chick embryo.

    PubMed

    Okafuji, Tatsuya; Tanaka, Hideaki

    2005-12-01

    We isolated a chick homologue of LINGO-1 (cLINGO-1), a novel component of the Nogo-66 receptor (NgR)/p75 neurotrophin receptor (NTR) signaling complex, and examined the expression of cLINGO-1 in the developing brain and spinal cord of the chick embryo by in situ hybridization and immunohistochemistry. cLINGO-1 was expressed broadly in the spinal cord, including the ventral portion of the ventricular zone, and motor neurons. cLINGO-1 was also expressed in the dorsal root ganglion and boundary cap cells at dorsal and ventral roots. In the early embryonic brain, cLINGO-1 was first expressed in the prosencephalon and the ventral mesencephalon, and later in the telencephalon, the rostral part of the mesencephalon and some parts of the hindbrain. cLINGO-1 was also expressed in the ventral part of the neural retina and trigeminal and facial nerves. We also found that cLINGO-1, cNgR1 and p75NTR were expressed in overlapped patterns in the spinal cord and the dorsal root ganglion, but that these genes were expressed in distinct patterns in the early embryonic brain.

  8. A Database of microRNA Expression Patterns in Xenopus laevis.

    PubMed

    Ahmed, Ayisha; Ward, Nicole J; Moxon, Simon; Lopez-Gomollon, Sara; Viaut, Camille; Tomlinson, Matthew L; Patrushev, Ilya; Gilchrist, Michael J; Dalmay, Tamas; Dotlic, Dario; Münsterberg, Andrea E; Wheeler, Grant N

    2015-01-01

    MicroRNAs (miRNAs) are short, non-coding RNAs around 22 nucleotides long. They inhibit gene expression either by translational repression or by causing the degradation of the mRNAs they bind to. Many are highly conserved amongst diverse organisms and have restricted spatio-temporal expression patterns during embryonic development where they are thought to be involved in generating accuracy of developmental timing and in supporting cell fate decisions and tissue identity. We determined the expression patterns of 180 miRNAs in Xenopus laevis embryos using LNA oligonucleotides. In addition we carried out small RNA-seq on different stages of early Xenopus development, identified 44 miRNAs belonging to 29 new families and characterized the expression of 5 of these. Our analyses identified miRNA expression in many organs of the developing embryo. In particular a large number were expressed in neural tissue and in the somites. Surprisingly none of the miRNAs we have looked at show expression in the heart. Our results have been made freely available as a resource in both XenMARK and Xenbase.

  9. Altered expression patterns of syndecan-1 and -2 predict biochemical recurrence in prostate cancer.

    PubMed

    Ledezma, Rodrigo; Cifuentes, Federico; Gallegos, Iván; Fullá, Juan; Ossandon, Enrique; Castellon, Enrique A; Contreras, Héctor R

    2011-05-01

    The clinical features of prostate cancer do not provide an accurate determination of patients undergoing biochemical relapse and are therefore not suitable as indicators of prognosis for recurrence. New molecular markers are needed for proper pre-treatment risk stratification of patients. Our aim was to assess the value of altered expression of syndecan-1 and -2 as a marker for predicting biochemical relapse in patients with clinically localized prostate cancer treated by radical prostatectomy. The expression of syndecan-1 and -2 was examined by immunohistochemical staining in a series of 60 paraffin-embedded tissue samples from patients with localized prostate cancer. Ten specimens from patients with benign prostatic hyperplasia were used as non-malignant controls. Semiquantitative analysis was performed to evaluate the staining patterns. To investigate the prognostic value, Kaplan-Meier survival curves were performed and compared by a log-rank test. In benign samples, syndecan-1 was expressed in basal and secretory epithelial cells with basolateral membrane localisation, whereas syndecan-2 was expressed preferentially in basal cells. In prostate cancer samples, the expression patterns of both syndecans shifted to granular-cytoplasmic localisation. Survival analysis showed a significant difference (P < 0.05) between normal and altered expression of syndecan-1 and -2 in free prostate-specific antigen recurrence survival curves. These data suggest that the expression of syndecan-1 and -2 can be used as a prognostic marker for patients with clinically localized prostate cancer, improving the prostate-specific antigen recurrence risk stratification.

  10. Altered expression patterns of syndecan-1 and -2 predict biochemical recurrence in prostate cancer

    PubMed Central

    Ledezma, Rodrigo; Cifuentes, Federico; Gallegos, Iván; Fullá, Juan; Ossandon, Enrique; Castellon, Enrique A; Contreras, Héctor R

    2011-01-01

    The clinical features of prostate cancer do not provide an accurate determination of patients undergoing biochemical relapse and are therefore not suitable as indicators of prognosis for recurrence. New molecular markers are needed for proper pre-treatment risk stratification of patients. Our aim was to assess the value of altered expression of syndecan-1 and -2 as a marker for predicting biochemical relapse in patients with clinically localized prostate cancer treated by radical prostatectomy. The expression of syndecan-1 and -2 was examined by immunohistochemical staining in a series of 60 paraffin-embedded tissue samples from patients with localized prostate cancer. Ten specimens from patients with benign prostatic hyperplasia were used as non-malignant controls. Semiquantitative analysis was performed to evaluate the staining patterns. To investigate the prognostic value, Kaplan–Meier survival curves were performed and compared by a log-rank test. In benign samples, syndecan-1 was expressed in basal and secretory epithelial cells with basolateral membrane localisation, whereas syndecan-2 was expressed preferentially in basal cells. In prostate cancer samples, the expression patterns of both syndecans shifted to granular-cytoplasmic localisation. Survival analysis showed a significant difference (P<0.05) between normal and altered expression of syndecan-1 and -2 in free prostate-specific antigen recurrence survival curves. These data suggest that the expression of syndecan-1 and -2 can be used as a prognostic marker for patients with clinically localized prostate cancer, improving the prostate-specific antigen recurrence risk stratification. PMID:21317913

  11. Noncanonical role of Hox14 revealed by its expression patterns in lamprey and shark.

    PubMed

    Kuraku, Shigehiro; Takio, Yoko; Tamura, Koji; Aono, Hideaki; Meyer, Axel; Kuratani, Shigeru

    2008-05-06

    Hox genes are arranged in uninterrupted clusters in vertebrate genomes, and the nested patterns of their expression define spatial identities in multiple embryonic tissues. The ancestral Hox cluster of vertebrates has long been thought to consist of, maximally, 13 Hox genes. However, recently, Hox14 genes were discovered in three chordate lineages, the coelacanth, cartilaginous fishes, and amphioxus, but their expression patterns have not yet been analyzed. We isolated Hox14 cDNAs from the Japanese lamprey and cloudy catshark. These genes were not expressed in the central nervous systems, somites, or fin buds/folds but were expressed in a restricted cell population surrounding the hindgut. The lack of Hox14 expression in most of the embryonic axial elements, where nested Hox expressions define spatial identities, suggests a decoupling of Hox14 genes' regulation from the ancestral regulatory mechanism. The relaxation of preexisting constraint for collinear expression may have permitted the secondary losses of this Hox member in the tetrapod and teleost lineages.

  12. Time-dependent expression patterns of cardiac aquaporins following myocardial infarction.

    PubMed

    Zhang, Hong Zhe; Kim, Moo Hyun; Lim, Ju Hyun; Bae, Hae-Rahn

    2013-03-01

    Aquaporins (AQPs) are expressed in myocardium and the implication of AQPs in myocardial water balance has been suggested. We investigated the expression patterns of AQP subtypes in normal myocardium and their changes in the process of edema formation and cardiac dysfunction following myocardial infarction (MI). Immunostaining demonstrated abundant expression of AQP1, AQP4, and AQP6 in normal mouse heart; AQP1 in blood vessels and cardiac myocytes, AQP4 exclusively on the intercalated discs between cardiac myocytes and AQP6 inside the myocytes. However, neither AQP7 nor AQP9 proteins were expressed in CD1 mouse myocardium. Echocardiography revealed that cardiac function was reduced at 1 week and recovered at 4 weeks after MI, whereas myocardial water content determined by wet-to-dry weight ratio increased at 1 week and rather reduced below the normal at 4 weeks. The expression of cardiac AQPs was up-regulated in MI-induced groups compared with sham-operated control group, but their time-dependent patterns were different. The time course of AQP4 expression coincided with that of myocardial edema and cardiac dysfunction following MI. However, expression of both AQP1 and AQP6 increased persistently up to 4 weeks. Our findings suggest a different role for cardiac AQPs in the formation and reabsorption of myocardial edema after MI.

  13. Time-Dependent Expression Patterns of Cardiac Aquaporins Following Myocardial Infarction

    PubMed Central

    Zhang, Hong Zhe; Kim, Moo Hyun; Lim, Ju Hyun

    2013-01-01

    Aquaporins (AQPs) are expressed in myocardium and the implication of AQPs in myocardial water balance has been suggested. We investigated the expression patterns of AQP subtypes in normal myocardium and their changes in the process of edema formation and cardiac dysfunction following myocardial infarction (MI). Immunostaining demonstrated abundant expression of AQP1, AQP4, and AQP6 in normal mouse heart; AQP1 in blood vessels and cardiac myocytes, AQP4 exclusively on the intercalated discs between cardiac myocytes and AQP6 inside the myocytes. However, neither AQP7 nor AQP9 proteins were expressed in CD1 mouse myocardium. Echocardiography revealed that cardiac function was reduced at 1 week and recovered at 4 weeks after MI, whereas myocardial water content determined by wet-to-dry weight ratio increased at 1 week and rather reduced below the normal at 4 weeks. The expression of cardiac AQPs was up-regulated in MI-induced groups compared with sham-operated control group, but their time-dependent patterns were different. The time course of AQP4 expression coincided with that of myocardial edema and cardiac dysfunction following MI. However, expression of both AQP1 and AQP6 increased persistently up to 4 weeks. Our findings suggest a different role for cardiac AQPs in the formation and reabsorption of myocardial edema after MI. PMID:23487012

  14. Differential mRNA expression patterns of the synaptotagmin gene family in the rodent brain.

    PubMed

    Mittelsteadt, Tobias; Seifert, Gerald; Alvárez-Barón, Elena; Steinhäuser, Christian; Becker, Albert J; Schoch, Susanne

    2009-02-01

    Synaptotagmins are a large family of membrane-trafficking proteins. They are evolutionarily conserved and have 15 members in rodents and humans. Synaptotagmins-1, -2, and -9, are known to have an essential role as calcium sensors for fast synaptic release. Synaptotagmin-7 is a major calcium sensor for the exocytosis of large secretory vesicles in endocrine cells. The functional roles of most synaptotagmin isoforms remain unknown. Here we examined whether synaptotagmins are expressed in the rodent brain in distinct patterns and whether individual neurons and astrocytes coexpress multiple synaptotagmin isoforms. We performed a systematic analysis of expression using radioactive in situ hybridization and quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR) as well as multiplex RT-PCR on a single-cell level. Our results demonstrate that most synaptotagmins are expressed in the rodent brain in highly distinctive expression patterns, and that individual neurons express variable subsets of different synaptotagmins. We also show that Syt-11 is the major isoform expressed in astrocytes. This study therefore supports the hypothesis that the functional properties of individual neurons and astrocytes are conferred by the specific subset of synaptotagmins expressed in a cell. 2008 Wiley-Liss, Inc.

  15. Expression patterns of IL-10 ligand and receptor gene families provide leads for biological characterization.

    PubMed

    Nagalakshmi, Marehalli L; Murphy, Erin; McClanahan, Terrill; de Waal Malefyt, Rene

    2004-05-01

    The expression patterns of the IL-10 ligand and receptor genes were examined in normal and transformed cell lines of human hematopoietic and non-hematopoietic origin. IL-10 family ligands, IL-10, IL-19, IL-20, IL-22, IL-24 and IL-26 were predominantly expressed by hematopoietic cells. IL-10, IL-24 and IL-26 were produced by both monocytes and T cells, IL-19 and IL-20 were produced by monocytes whereas IL-22 was produced mainly by activated T cells. The receptors of the IL-10 family, IL-10R1, IL-10R2, IL-20R1, IL-20R2, IL-22R1 and IL-22 BP were also expressed in a distinct pattern when probed on these cell lines. The expression of IL-10R2 was ubiquitous whereas IL-10R1 was predominantly expressed on hematopoietic cells, including, T cells, B cells, NK cells, monocytes and dendritic cells. IL-20R1, IL-20R2 and IL-22R1 were absent or expressed at extremely low levels on cells of the hematopoietic lineage. These receptors were mainly found on epithelial and stromal cells fibroblasts of various tissues. Interestingly, IL-22BP was quite specifically expressed by dendritic cells. These data point to a function of the novel IL-10 family members in communication and interaction between cells of the hematopoietic and non-hematopoietic lineages, a role quite distinct from the immunomodulating effects of IL-10 itself.

  16. Gene association analysis: a survey of frequent pattern mining from gene expression data.

    PubMed

    Alves, Ronnie; Rodriguez-Baena, Domingo S; Aguilar-Ruiz, Jesus S

    2010-03-01

    Establishing an association between variables is always of interest in genomic studies. Generation of DNA microarray gene expression data introduces a variety of data analysis issues not encountered in traditional molecular biology or medicine. Frequent pattern mining (FPM) has been applied successfully in business and scientific data for discovering interesting association patterns, and is becoming a promising strategy in microarray gene expression analysis. We review the most relevant FPM strategies, as well as surrounding main issues when devising efficient and practical methods for gene association analysis (GAA). We observed that, so far, scalability achieved by efficient methods does not imply biological soundness of the discovered association patterns, and vice versa. Ideally, GAA should employ a balanced mining model taking into account best practices employed by methods reviewed in this survey. Integrative approaches, in which biological knowledge plays an important role within the mining process, are becoming more reliable.

  17. Molecular characterization and expression pattern of the porcine STARS, a striated muscle-specific expressed gene.

    PubMed

    Peng, Y B; Guan, H P; Fan, B; Zhao, S H; Xu, X W; Li, K; Zhu, M J; Yerle, M; Liu, B

    2008-10-01

    STARS (striated muscle activator of Rho signaling) promotes the nuclear localization of MRTFs and mediates SRF transcription, which provides a potential muscle-specific mechanism for linking changes in the actin cytoskeleton structure with muscle gene expression. In this study, the full-length cDNA of the porcine STARS was cloned. The open reading frame of this gene contains 1,155 bp and encodes a protein of 384 amino acids, which is 79, 73, and 77% identical with human, mouse, and rat STARS genes, respectively. RT-PCR revealed that STARS is specifically expressed in heart and skeletal muscles. STARS is also distinctly different in different muscle developmental stages. The result indicates that its expression increased gradually from 33 dpc (days postcoitum) to postnatal muscles, and peaked 28 days postnatal. The porcine STARS was mapped to SSC4p13 using the somatic cell hybrid panel and the radiation hybrid panel IMpRH (LOD score 11.98). The data show that STARS is closely linked to marker SW871. A T/G single nucleotide polymorphism in the coding sequence, detected as Bsh1236I PCR-RFLP, displays allele frequency differences in six pig breeds.

  18. Patterns of gene expressions induced by arsenic trioxide in cultured human fibroblasts.

    PubMed

    Burnichon, Vanina; Jean, Séverine; Bellon, Laurence; Maraninchi, Marie; Bideau, Chantal; Orsière, Thierry; Margotat, Alain; Gérolami, Victoria; Botta, Alain; Bergé-Lefranc, Jean Louis

    2003-07-20

    Arsenic exposure is associated with several human diseases and particularly, with neoplasia. Although the mechanism of arsenic toxicity is not fully understood, several recent works pointed out the involvement of oxidative stress in arsenic-induced DNA damage that, in living cells, correlates with changes in gene expressions. In cultured human fibroblasts exposed for 24 h to micromolar arsenic concentrations, we studied, using real-time RT-PCR, the expression profile of a limited number of genes: genes coding for a stress protein (HSP70), transcription factors (cJUN, cFOS, ETR103, ETR101 and TTP) and cell cycle or DNA repair proteins (P21, GADD153). We observed that the expression profile of genes followed individual different patterns that can be summed up in early-transient gene expression by contrast to delayed gene expression.

  19. In silico dissection of cell-type-associated patterns of gene expression in prostate cancer

    PubMed Central

    Stuart, Robert O.; Wachsman, William; Berry, Charles C.; Wang-Rodriguez, Jessica; Wasserman, Linda; Klacansky, Igor; Masys, Dan; Arden, Karen; Goodison, Steven; McClelland, Michael; Wang, Yipeng; Sawyers, Anne; Kalcheva, Iveta; Tarin, David; Mercola, Dan

    2004-01-01

    Prostate tumors are complex entities composed of malignant cells mixed and interacting with nonmalignant cells. However, molecular analyses by standard gene expression profiling are limited because spatial information and nontumor cell types are lost in sample preparation. We scored 88 prostate specimens for relative content of tumor, benign hyperplastic epithelium, stroma, and dilated cystic glands. The proportions of these cell types were then linked in silico to gene expression levels determined by microarray analysis, revealing unique cell-specific profiles. Gene expression differences for malignant and nonmalignant epithelial cells (tumor versus benign hyperplastic epithelium) could be identified without being confounded by contributions from stroma that dominate many samples or sacrificing possible paracrine influences. Cell-specific expression of selected genes was validated by immunohistochemistry and quantitative PCR. The results provide patterns of gene expression for these three lineages with relevance to pathogenetic, diagnostic, and therapeutic considerations. PMID:14722351

  20. Divergent expression patterns of Sox9 duplicates in teleosts indicate a lineage specific subfunctionalization.

    PubMed

    Klüver, Nils; Kondo, Mariko; Herpin, Amaury; Mitani, Hiroshi; Schartl, Manfred

    2005-06-01

    Sry-related HMG-box genes are key regulators of several developmental processes. Sox9 encodes a transcription factor required for cartilage formation and testis determination in mammals. In zebrafish (Danio rerio) and stickleback (Gasterosteus aculeatus) two co-orthologs of Sox9 are present. To date, only one Sox9 had been identified in medaka (Oryzias latipes). We have now isolated the second Sox9 gene. Sequence analysis, phylogenetic data, linkage mapping as well as expression pattern all together suggest that the medaka Sox9a and Sox9b are co-orthologs. During embryogenesis, the expression pattern of Sox9a and Sox9b are distinct but overlap considerably in craniofacial cartilage elements. Comparing the zebrafish Sox9a and Sox9b expression patterns with medaka Sox9a and Sox9b expression domains revealed that some are identical but others are clearly different. We conclude that Sox9 regulatory subfunctions were not partitioned before divergence of the teleosts and evolved to lineage-specific expression domains.

  1. Expression Pattern of Fatty Acid Binding Proteins in Celiac Disease Enteropathy

    PubMed Central

    Bottasso Arias, Natalia M.; García, Marina; Bondar, Constanza; Guzman, Luciana; Redondo, Agustina; Chopita, Nestor; Córsico, Betina; Chirdo, Fernando G.

    2015-01-01

    Celiac disease (CD) is an immune-mediated enteropathy that develops in genetically susceptible individuals following exposure to dietary gluten. Severe changes at the intestinal mucosa observed in untreated CD patients are linked to changes in the level and in the pattern of expression of different genes. Fully differentiated epithelial cells express two isoforms of fatty acid binding proteins (FABPs): intestinal and liver, IFABP and LFABP, respectively. These proteins bind and transport long chain fatty acids and also have other important biological roles in signaling pathways, particularly those related to PPARγ and inflammatory processes. Herein, we analyze the serum levels of IFABP and characterize the expression of both FABPs at protein and mRNA level in small intestinal mucosa in severe enteropathy and normal tissue. As a result, we observed higher levels of circulating IFABP in untreated CD patients compared with controls and patients on gluten-free diet. In duodenal mucosa a differential FABPs expression pattern was observed with a reduction in mRNA levels compared to controls explained by the epithelium loss in severe enteropathy. In conclusion, we report changes in FABPs' expression pattern in severe enteropathy. Consequently, there might be alterations in lipid metabolism and the inflammatory process in the small intestinal mucosa. PMID:26346822

  2. [Expression patterns of amelogenin and enamelin in developing mouse tooth germs].

    PubMed

    Tian, Hua; Lü, Ping; Zhou, Chun-yan; Gao, Xue-jun

    2012-03-01

    To invesitgate the expression patterns of amelogenin and enamelin in the developing tooth germs. Mandible sections of postnatal day 1, 3, 7 and 14 mouse were prepared, immunohistochemical analysis and reverse transcriptase polymerase chain reaction (RT-PCR) were performed to detect the expression patterns of amelogenin and enamelin in mandibular first molars. Amelogenin was observed in the cytoplasm of secretory ameloblasts and the whole enamel matrix layer. It was also transiently expressed in the odontoblasts of postnatal day 1 molars. Enamelin proteins were observed in the enamel layer deposited by secretory ameloblasts, especially intense beneath the ameloblast process and dentino-enamel junction. The mRNA levels of both amelogenin and enamelin were highest on postnatal day 7 (the ratio to glyceraldehyde phosphate dehydrogenase of amelogenin and enamelin: 0.813 ± 0.085 and 0.799 ± 0.064, respectively, P < 0.05). Amelogenin and enamelin were enamel matrix proteins predominately expressed by secretory ameloblasts. The temporal-spatial expression patterns of amelogenin and enamelin indicate the important roles they played in amelogenesis and biomineralization.

  3. A tool for identification of genes expressed in patterns of interest using the Allen Brain Atlas

    PubMed Central

    Davis, Fred P.; Eddy, Sean R.

    2009-01-01

    Motivation: Gene expression patterns can be useful in understanding the structural organization of the brain and the regulatory logic that governs its myriad cell types. A particularly rich source of spatial expression data is the Allen Brain Atlas (ABA), a comprehensive genome-wide in situ hybridization study of the adult mouse brain. Here, we present an open-source program, ALLENMINER, that searches the ABA for genes that are expressed, enriched, patterned or graded in a user-specified region of interest. Results: Regionally enriched genes identified by ALLENMINER accurately reflect the in situ data (95–99% concordance with manual curation) and compare with regional microarray studies as expected from previous comparisons (61–80% concordance). We demonstrate the utility of ALLENMINER by identifying genes that exhibit patterned expression in the caudoputamen and neocortex. We discuss general characteristics of gene expression in the mouse brain and the potential application of ALLENMINER to design strategies for specific genetic access to brain regions and cell types. Availability: ALLENMINER is freely available on the Internet at http://research.janelia.org/davis/allenminer. Contact: davisf@janelia.hhmi.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19414530

  4. Expression pattern of INNER NO OUTER homologue in Nymphaea (water lily family, Nymphaeaceae).

    PubMed

    Yamada, Toshihiro; Ito, Motomi; Kato, Masahiro

    2003-10-01

    Two homologues of INNER NO OUTER ( INO) in Nymphaea alba and N. colorata (Nymphaeaceae) were isolated and the expression pattern of the N. alba INO homologue NaINO was examined by in situ hybridization. The INO homologues obtained have a portion similar to INO in the predicted amino acid sequences between the conserved zinc finger-like and YABBY domains. In an in situ hybridization analysis, NaINO is expressed in the outer epidermis of the outer integument, inner integument, and the tip of the nucellus. The pattern observed in the outer integument is very similar to that of Arabidopsis thaliana, while the expression in the inner integument and nucellus is not observed in A. thaliana.

  5. Temporal and spatial patterning of transgene expression by near-infrared irradiation

    PubMed Central

    Gomez, Leyre; Lopez, Daniel; Arruebo, Manuel; Wilson, Christopher G; Franceschi, Renny T.; Voellmy, Richard; Santamaria, Jesus; Vilaboa, Nuria

    2014-01-01

    We investigated whether near-infrared (NIR) light could be employed for patterning transgene expression in plasmonic cell constructs. Hollow gold nanoparticles with a plasmon surface band absorption peaking at ~750 nm, a wavelength within the so called “tissue optical window”, were used as fillers in fibrin-based hydrogels. These composites, which efficiently transduce NIR photon energy into heat, were loaded with genetically-modified cells that harbor a heat-activated and ligand-dependent gene switch for regulating transgene expression. NIR laser irradiation in the presence of ligand triggered 3-dimensional patterns of transgene expression faithfully matching the illuminated areas of plasmonic cell constructs. This noninvasive technology was proven useful for remotely controlling in vivo the spatiotemporal bioavailability of transgenic vascular endothelial growth factor. The combination of spatial control by means of NIR irradiation along with safe and timed transgene induction presents a high application potential for engineering tissues in regenerative medicine scenarios. PMID:24957294

  6. Expression Patterns of CREBs in Oocyte Growth and Maturation of Fish

    PubMed Central

    Wang, De-Shou; Sudhakumari, Cheni-Chery; Kobayashi, Tohru; Nagahama, Yoshitaka

    2015-01-01

    In fish, oocyte meiotic maturation is regulated by 17α, 20β-dihydroxy-progesterone through cAMP. To study the role of cAMP response element binding protein (CREB) in meiotic maturation, we cloned and characterized the expression pattern of CREBs from two fish models, the Nile tilapia and catfish. In the Nile tilapia three different CREBs were identified where in CREB1 was found in many tissues including gonads with abundant expression in testis. CREB2, few amino acids shorter than CREB1, was expressed in several tissues with abundant expression in ovary. In addition, a 3’UTR variant form, CREB3 was exclusively found in ovary. During natural 14-day ovarian cycle of the Nile tilapia, CREB1 expression was stable throughout vitellogenesis with a sharp decrease on the day of spawning. In contrast, CREB2 remain unchanged throughout the ovarian cycle, however elevated in 11-day full-grown immature ovarian follicle and after hCG-induction. Interestingly, CREB3 expression was induced three folds on the day of spawning as well as during hCG-induced oocyte maturation. Based on the synergistic expression pattern, CREB1 is likely to control oocyte growth, whereas CREB 2 and 3 contribute to oocyte maturation in tilapia and the latter seems to be critical. In catfish, a single form of CREB showed a maximum expression during spawning phase and hCG-induced maturation both in vivo and in vitro augmented CREB expression. These results suggest that spatial and temporal expression of CREBs seems to be important for final oocyte maturation and may also regulate oocyte growth in fish. PMID:26700177

  7. β-Catenin Expression Pattern in Stage I and II Ovarian Carcinomas

    PubMed Central

    Gamallo, Carlos; Palacios, José; Moreno, Gema; Calvo de Mora, Jorge; Suárez, Asunción; Armas, Alvaro

    1999-01-01

    The immunohistochemical expression pattern of β-catenin has been correlated with β-catenin gene mutations, clinicopathological features, and disease outcome in 69 stage I and II ovarian carcinomas. β-Catenin expression was localized in the nuclei, in addition to the cytoplasm and membrane, in 11 tumors (16%): nine endometrioid carcinomas with widespread nuclear expression and two serous carcinomas with focal nuclear expression. The remaining 58 carcinomas (84%) only had membranous β-catenin expression. All but one of the endometrioid carcinomas with nuclear β-catenin expression had considerable squamous metaplasia, and five of these cases had large areas of endometrioid tumor of low malignant potential. In addition, β-catenin nuclear expression was observed in atypical epithelial cells in endometriotic glands adjacent to an endometrioid carcinoma. Sequencing was performed on 25 tumors and corresponding normal tissue: all 13 endometrioid tumors as well as 12 carcinomas of other histological types (four serous, two clear cell, two mucinous, and two mixed). There were oncogenic mutations in the phosphorylation sequence for GSK-3β in exon 3 of the β-catenin gene in seven endometrioid carcinomas with β-catenin nuclear expression. Three mutations affected codon 32 (D32G, D32Y, and D32Y), one affected codon 33 (S33C), two affected codon 37 (S37C and S37F), and one affected codon 41 (T41A). No mutations were observed in the other 18 carcinomas analyzed, comprising two endometrioid and two serous carcinomas with β-catenin nuclear expression, and 14 carcinomas of different histological types with only membranous expression. In the univariate and multivariate survival analyses, β-catenin nuclear expression was selected as an indicator of good prognosis, because no patient whose tumor expressed β-catenin in the nuclei showed relapses or died, in contrast to the 19 relapses and deaths among patients with tumors that only had β-catenin membranous expression

  8. The expression patterns of vascular endothelial growth factor and thrombospondin 2 after corneal alkali burn.

    PubMed

    Yan, Jun; Zeng, Yijun; Jiang, Jianxin; Zhou, Jihong; Yin, Zhiyong; Wang, Zhengguo; Zhu, Peifang

    2007-10-15

    The aim of the investigation was to explore the expression patterns of VEGF and TSP2 after corneal alkali burn in vivo. After the model of corneal alkali burn was established in mice, the expression levels of VEGF and TSP2 were determined by immunohistochemistry (IHC), RT-PCR, image analysis and statistical evaluation. Compared with control group, the expression level of VEGF increased significantly at 6h after alkali burn and reached its maximum at 12h. Then, it increased again till the second peak appeared at 96h and 192h. The VEGF-positive reaction mainly gathered in the stroma of cornea. On the other hand, the expression of TSP2 enhanced at 3h and attained two peaks at 6h and 96h, respectively, with the process of wound healing. TSP2 was expressed mainly in the base of epithelial layer. The expression patterns of VEGF and TSP2 reflect the complicated interaction with many factors including promoted and inhibited vascularization in vivo. Moreover, it might provide a novel method for controlling vascular hyperplasia in future clinical work according to the data of VEGF and TSP2.

  9. Genome-wide gene expression patterns in dikaryon of the basidiomycete fungus Pleurotus ostreatus.

    PubMed

    Liu, Tianxiang; Li, Huiru; Ding, Yatong; Qi, Yuancheng; Gao, Yuqian; Song, Andong; Shen, Jinwen; Qiu, Liyou

    Dikarya is a subkingdom of fungi that includes Ascomycota and Basidiomycota. The gene expression patterns of dikaryon are poorly understood. In this study, we bred a dikaryon DK13×3 by mating monokaryons MK13 and MK3, which were from the basidiospores of Pleurotus ostreatus TD300. Using RNA-Seq, we obtained the transcriptomes of the three strains. We found that the total transcript numbers in the transcriptomes of the three strains were all more than ten thousand, and the expression profile in DK13×3 was more similar to MK13 than MK3. However, the genes involved in macromolecule utilization, cellular material synthesis, stress-resistance and signal transduction were much more up-regulated in the dikaryon than its constituent monokaryons. All possible modes of differential gene expression, when compared to constituent monokaryons, including the presence/absence variation, and additivity/nonadditivity gene expression in the dikaryon may contribute to heterosis. By sequencing the urease gene poure sequences and mRNA sequences, we identified the monoallelic expression of the poure gene in the dikaryon, and its transcript was from the parental monokaryon MK13. Furthermore, we discovered RNA editing in the poure gene mRNA of the three strains. These results suggest that the gene expression patterns in dikaryons should be similar to that of diploids during vegetative growth. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

  10. Expression patterns of Wnt genes in the venom claws of centipedes.

    PubMed

    Hayden, Luke; Arthur, Wallace

    2013-01-01

    The venom claws of centipedes, also known as forcipules, represent an evolutionary novelty that must have arisen in the centipede stem species, as they are not found in any other myriapods. The developmental-genetic changes that are involved in the origin of novelties are of considerable interest. It has previously been shown that centipede forcipules have a unique Hox code. However, this is a combinatorial code: no single Hox gene has a forcipule-specific expression. Here, we focus on Wnt genes. Two genes of this family show forcipule-specific expression in the "model centipede" Strigamia maritima: Wnt7 and Wnt11. For Wnt7, this forcipular expression zone seems to be a new one, which has arisen in evolution subsequently to other expression zones of the same gene. However, for Wnt11, the forcipule-specific expression probably arose by reduction of a more general pattern that originally included most or all of the limbs of an ancestral myriapod. Thus the developmental-genetic basis of the evolutionary change that turned the first pair of walking legs into venom claws is complex, involving different types of change in expression pattern. This sort of complexity is likely to be the case regarding evolutionary changes in morphology in general. Whether the origins of those features that can be considered as novelties are different in terms of their developmental-genetic basis from more routine evolutionary changes remains an open question.

  11. Spatiotemporal patterns of expression of IGSF4 in developing mouse nervous system.

    PubMed

    Ohta, Yoshimi; Itoh, Kyoko; Yaoi, Takeshi; Tando, So; Fukui, Kenji; Fushiki, Shinji

    2005-04-21

    IGSF4 is a novel immunoglobulin (Ig)-like intercellular adhesion molecule. Since IGSF4 has been characterized by several independent research groups, this molecule is called by three names, TSLC1, SgIGSF and SynCAM. In the experiments to study global changes of gene expression in fetal murine brains after prenatal exposure to low-doses of X-rays, we have found IGSF4 as one of down-regulated genes after X-irradiation. In order to elucidate the expression of spatiotemporal expression of IGSF4 in the developing brain, we have produced polyclonal antibody against IGSF4 and studied the expression of IGSF4 with immunohistochemistry and Western blot analysis. At embryonic day (E) 12.5, IGSF4-immunoreactivity (IR) was observed diffusely in the telencephalic wall, whereas it became rather confined to the subplate, the cortical plate and the subventricular zone as the development proceeded. Noteworthy was a distinct radial pattern found in the cortical plate of E16.5. IGSF4-IR gradually decreased after birth and disappeared in adulthood. In the cerebellum, IGSF4 was expressed in the molecular layer at postnatal day (P) 0 through P14. By Western blot analysis, IGSF4 remained at low levels throughout embryonic stage, whereas it increased after birth. These spatiotemporal patterns of the expression suggest that IGSF4 plays crucial roles in the development of both telencephalon and cerebellum.

  12. Genome-wide expression patterns of calcium-dependent protein kinases in Toxoplasma gondii.

    PubMed

    Wang, Jin-Lei; Huang, Si-Yang; Zhang, Nian-Zhang; Chen, Jia; Zhu, Xing-Quan

    2015-06-04

    Calcium-dependent protein kinases (CDPKs) are found in plants and some Apicomplexan parasites but not in animals or fungi. CDPKs have been shown to play important roles in various calcium-signaling pathways such as host cell invasion, egress and protein secretion in Toxoplasma gondii. The objectives of the present study were to examine the T. gondii CDPK genes expression patterns during different development stages and stress responses. We carried out a comprehensive expression analysis of CDPK genes based on previously published microarray datasets, and we also used real time quantitative RT-PCR to study ten T. gondii CDPK genes expression patterns under acid, alkali, high temperature and low temperature conditions. Microarrays analysis indicated that some TgCDPK genes exhibited different expression levels in IFN-γ stimuli conditions or at different developmental stages, suggesting that CDPK genes may play different roles in these processes. Expression profiles under low temperature, high temperature, acid and alkaline indicated that most CDPK may be involved in regulating high temperature, acid and alkaline signaling pathways. We present a genome-wide expression analysis of CDPK genes in T. gondii for the first time, and the mRNA levels change with abiotic and biotic stresses, suggesting their functional roles in these processes. These results will provide a solid basis for future functional studies of the CDPK gene family in T. gondii.

  13. Claudin gene expression patterns do not associate with interspecific differences in paracellular nutrient absorption.

    PubMed

    Price, Edwin R; Rott, Katherine H; Caviedes-Vidal, Enrique; Karasov, William H

    2016-01-01

    Bats exhibit higher paracellular absorption of glucose-sized molecules than non-flying mammals, a phenomenon that may be driven by higher permeability of the intestinal tight junctions. The various claudins, occludin, and other proteins making up the tight junctions are thought to determine their permeability properties. Here we show that absorption of the paracellular probe l-arabinose is higher in a bat (Eptesicus fuscus) than in a vole (Microtus pennsylvanicus) or a hedgehog (Atelerix albiventris). Furthermore, histological measurements demonstrated that hedgehogs have many more enterocytes in their intestines, suggesting that bats cannot have higher absorption of arabinose simply by having more tight junctions. We therefore investigated the mRNA levels of several claudins and occludin, because these proteins may affect permeability of tight junctions to macronutrients. To assess the expression levels of claudins per tight junction, we normalized the mRNA levels of the claudins to the constitutively expressed tight junction protein ZO-1, and combined these with measurements previously made in a bat and a rodent to determine if there were among-species differences. Although expression ratios of several genes varied among species, there was not a consistent difference between bats and non-flyers in the expression ratio of any particular gene. Protein expression patterns may differ from mRNA expression patterns, and might better explain differences among species in arabinose absorption.

  14. Expression pattern of Piwi-like genes in adult Myzostoma cirriferum (Annelida).

    PubMed

    Weigert, Anne; Helm, Conrad; Hausen, Harald; Zakrzewski, Anne-C; Bleidorn, Christoph

    2013-09-01

    Piwi-like genes are a subgroup of Argonaute genes which participate as gene regulators by gene silencing. In most bilaterians, such as mouse, human, insects, and zebrafish, their expression is mostly limited to gonadal stem cells. But there are some striking exceptions to this pattern; flatworms and acoels also express Piwi-like genes in somatic stem cells, due to their unique replacement system. Annelid species like Capitella teleta and Platynereis dumerilii express these genes in cells of the posterior growth zone as well as in gonadal stem cells. To investigate the expression pattern of Piwi-like genes in another annelid, we established in situ hybridization for adult Myzostoma cirriferum. Piwi-like gene transcripts recovered in an mRNA-seq library of pooled adult stages of M. cirriferum were expanded using RACE PCR, cloned and sequenced. ML analysis confirmed the identity of both transcripts as part of the Piwi1-like or Piwi2-like subfamily of Argonaute proteins. The results of in situ hybridization studies show that the expression of both Piwi-like genes, Mc-Piwi1 and Mc-Piwi2, is clearly located only in gonadal stem cells, and as such we did not find any evidence for the existence of a posterior growth zone nor expression in somatic stem cells.

  15. Chromatophore Activity during Natural Pattern Expression by the Squid Sepioteuthis lessoniana: Contributions of Miniature Oscillation

    PubMed Central

    Suzuki, Mamiko; Kimura, Tetsuya; Ogawa, Hiroto; Hotta, Kohji; Oka, Kotaro

    2011-01-01

    Squid can rapidly change the chromatic patterns on their body. The patterns are created by the expansion and retraction of chromatophores. The chromatophore consists of a central pigment-containing cell surrounded by radial muscles that are controlled by motor neurons located in the central nervous system (CNS). In this study we used semi-intact squid (Sepioteuthis lessoniana) displaying centrally controlled natural patterns to analyze spatial and temporal activities of chromatophores located on the dorsal mantle skin. We found that chromatophores oscillated with miniature expansions/retractions at various frequencies, even when the chromatic patterns appear macroscopically stable. The frequencies of this miniature oscillation differed between “feature” and “background” areas of chromatic patterns. Higher frequencies occurred in feature areas, whereas lower frequencies were detected in background areas. We also observed synchronization of the oscillation during chromatic pattern expression. The expansion size of chromatophores oscillating at high frequency correlated with the number of synchronized chromatophores but not the oscillation frequency. Miniature oscillations were not observed in denervated chromatophores. These results suggest that miniature oscillations of chromatophores are driven by motor neuronal activities in the CNS and that frequency and synchrony of this oscillation determine the chromatic pattern and the expansion size, respectively. PMID:21483763

  16. Unique expression patterns of cell fate molecules delineate sequential stages of dentate gyrus development.

    PubMed

    Pleasure, S J; Collins, A E; Lowenstein, D H

    2000-08-15

    The dentate gyrus of the hippocampus is uniquely organized with a displaced proliferative zone that continues to generate dentate granule cells throughout life. We have analyzed the expression of Notch receptors, Notch ligands, and basic helix-loop-helix (bHLH) genes during dentate gyrus development to determine whether the need to maintain a pool of undifferentiated precursors is reflected in the patterns of expression of these genes. Many of these genes are expressed diffusely throughout the cortical neuroepithelium at embryonic days 16 and 17 in the rat, just preceding the migration of newly born granule cells and dentate precursor cells into the dentate anlage. However, at this time, Mash1, Math3, and Id3 expression are all concentrated in the area that specifically gives rise to granule cells and dentate precursor cells. Two days later, at the time of migration of the first granule cells and dentate precursor cells, cells expressing Mash1 are seen in the migratory route from the subventricular zone to the developing dentate gyrus. Newly born granule cells expressing NeuroD are also present in this migratory pathway. In the first postnatal week, precursor cells expressing Mash1 reside in the dentate hilus, and by the third postnatal week they have largely taken up their final position in the subgranular zone along the hilar side of the dentate granule cell layer. After terminal differentiation, granule cells born in the hilus or the subgranular zone begin to express NeuroD followed by NeuroD2. This study establishes that the expression patterns of bHLH mRNAs evolve during the formation of the dentate gyrus, and the precursor cells resident in the mature dentate gyrus share features with precursor cells found in development. Thus, many of the same mechanisms that are known to regulate cell fate and precursor pool size in other brain regions are likely to be operative in the dentate gyrus at all stages of development.

  17. Temporal and spatial pattern of dref expression during Drosophila bristle development.

    PubMed

    Kawamori, Akihito; Shimaji, Kouhei; Yamaguchi, Masamitsu

    2013-01-01

    The DNA replication-related element-binding factor (DREF) is a BED finger-type transcription factor that has important roles in cell cycle progression. In an earlier study, we showed that DREF is required for endoreplication during posterior scutellar macrochaete development. However, dynamic change in the dref expression in the cell lineage is unclear. In this study, we focused on the spatio-temporal pattern of expression of the dref gene during bristle development. Gene expression analysis using GAL4 enhancer trap lines of dref and the upstream activation sequence-green fluorescent protein with nuclear localization signals (UAS-GFPnls) in combination with immunostaining revealed the half-life of GFPnls in vivo (<6 hours) is short enough to monitor the dref gene expression. The analysis revealed that the dref expression occurs in clusters that include cells consisting of a bristle as well as surrounding epidermal cells. The intensity of GFP signals was almost the same in those cells, suggesting expression of the dref gene in bristle cell lineages occurs simultaneously in clusters. Further analysis showed that GFP signals increased twice during sensory organ precursor development as well as in bristle development at 9 hours and 15 hours after pupal formation, respectively. However, its expression was barely detectable in the cell lineages in and around asymmetric cell division or at other stages of development. For the first time, we clarified a spatio-temporal pattern of expression of the dref gene in vivo and revealed that expression of the dref gene occurs in clusters and is temporally regulated at specific times during bristle development.

  18. Combination of gene expression patterns in whole blood discriminate between tuberculosis infection states

    PubMed Central

    2014-01-01

    Background Genetic factors are involved in susceptibility or protection to tuberculosis (TB). Apart from gene polymorphisms and mutations, changes in levels of gene expression, induced by non-genetic factors, may also determine whether individuals progress to active TB. Methods We analysed the expression level of 45 genes in a total of 47 individuals (23 healthy household contacts and 24 new smear-positive pulmonary TB patients) in Addis Ababa using a dual colour multiplex ligation-dependent probe amplification (dcRT-MLPA) technique to assess gene expression profiles that may be used to distinguish TB cases and their contacts and also latently infected (LTBI) and uninfected household contacts. Results The gene expression level of BLR1, Bcl2, IL4d2, IL7R, FCGR1A, MARCO, MMP9, CCL19, and LTF had significant discriminatory power between sputum smear-positive TB cases and household contacts, with AUCs of 0.84, 0.81, 0.79, 0.79, 0.78, 0.76, 0.75, 0.75 and 0.68 respectively. The combination of Bcl2, BLR1, FCGR1A, IL4d2 and MARCO identified 91.66% of active TB cases and 95.65% of household contacts without active TB. The expression of CCL19, TGFB1, and Foxp3 showed significant difference between LTBI and uninfected contacts, with AUCs of 0.85, 0.82, and 0.75, respectively, whereas the combination of BPI, CCL19, FoxP3, FPR1 and TGFB1 identified 90.9% of QFT- and 91.6% of QFT+ household contacts. Conclusions Expression of single and especially combinations of host genes can accurately differentiate between active TB cases and healthy individuals as well as between LTBI and uninfected contacts. PMID:24885723

  19. Cellular differentiation in the emerging fetal rat small intestinal epithelium: mosaic patterns of gene expression.

    PubMed

    Rubin, D C; Ong, D E; Gordon, J I

    1989-02-01

    We have examined the pattern of differentiation of the small intestinal epithelium in fetal rats during the 17th through 21st days of gestation. Five genes expressed in late fetal, neonatal, and adult enterocytes were used as markers of differentiation. They encode three homologous small cytoplasmic hydrophobic ligand binding proteins--liver fatty acid binding protein (L-FABP), intestinal fatty acid binding protein (I-FABP), and cellular retinol binding protein II (CRBP II)--and two apolipoproteins--apoAI and apoAIV. RNA blot hybridization studies indicated that gradients in mRNA concentration from the proximal small intestine to colon appear coincident with the initiation of rapid epithelial cell proliferation and villus formation (days 17-19 of the 22-day gestation period). Immunocytochemical studies disclosed a remarkably heterogeneous pattern of cell-specific expression of the three hydrophobic ligand binding proteins that was not apparent with either apoAIV or apoAI. This "mosaic" staining pattern was observed in morphologically similar cells occupying identical topographic positions along nascent villi in 17- to 18-day fetuses. The onset and resolution of this mosaicism varies between I-FABP, L-FABP, and CRBP II in the proximal small bowel, although it completely resolves by the first postnatal day. The distal small intestine exhibits a developmental delay of 1-2 days in the appearance of this heterogeneous pattern of initial gene expression. Double-label immunofluorescent analyses using L-FABP and I-FABP antibodies indicated that on the 18th day of gestation the proximal small intestinal columnar epithelium contains several populations of enterocytes expressing neither, one, or both proteins. The potential significance of this mosaic pattern of intestinal epithelial differentiation is discussed in light of recent studies with transgenic and chimeric mice.

  20. A Synthesis Method of Gene Networks Having Cyclic Expression Pattern Sequences by Network Learning

    NASA Astrophysics Data System (ADS)

    Mori, Yoshihiro; Kuroe, Yasuaki

    Recently, synthesis of gene networks having desired functions has become of interest to many researchers because it is a complementary approach to understanding gene networks, and it could be the first step in controlling living cells. There exist several periodic phenomena in cells, e.g. circadian rhythm. These phenomena are considered to be generated by gene networks. We have already proposed synthesis method of gene networks based on gene expression. The method is applicable to synthesizing gene networks possessing the desired cyclic expression pattern sequences. It ensures that realized expression pattern sequences are periodic, however, it does not ensure that their corresponding solution trajectories are periodic, which might bring that their oscillations are not persistent. In this paper, in order to resolve the problem we propose a synthesis method of gene networks possessing the desired cyclic expression pattern sequences together with their corresponding solution trajectories being periodic. In the proposed method the persistent oscillations of the solution trajectories are realized by specifying passing points of them.

  1. Expression Pattern of ERF Gene Family under Multiple Abiotic Stresses in Populus simonii × P. nigra.

    PubMed

    Yao, Wenjing; Zhang, Xuemei; Zhou, Boru; Zhao, Kai; Li, Renhua; Jiang, Tingbo

    2017-01-01

    Identification of gene expression patterns of key genes across multiple abiotic stresses is critical for mechanistic understanding of stress resistance in plant. In the present study, we identified differentially expressed genes (DEGs) in di-haploid Populus simonii × P. nigra under respective stresses of NaCl, KCl, CdCl2, and PEG. On the basis of RNA-Seq, we detected 247 DEGs that are shared by the four stresses in wild type poplar, and mRNA abundance of the DEGs were validated in transgenic poplar overexpressing ERF76 gene by RNA-Seq and RT-qPCR. Results from gene ontology analysis indicated that these genes are enriched in significant pathways, such as phenylpropanoid biosynthesis, phenylalanine metabolism, starch and sucrose metabolism, and plant hormone signal transduction. Ethylene response factor (ERF) gene family plays significant role in plant abiotic stress responses. We also investigated expression pattern of ERF gene family under the four stresses. The ERFs and DEGs share similar expression pattern across the four stresses. The transgenic poplar is superior to WT in morphologic, physiological and biochemical traits, which demonstrated the ERF76 gene plays a significant role in stress resistance. These studies will give a rise in understanding the stress response mechanisms in poplar.

  2. Expression Pattern of ERF Gene Family under Multiple Abiotic Stresses in Populus simonii × P. nigra

    PubMed Central

    Yao, Wenjing; Zhang, Xuemei; Zhou, Boru; Zhao, Kai; Li, Renhua; Jiang, Tingbo

    2017-01-01

    Identification of gene expression patterns of key genes across multiple abiotic stresses is critical for mechanistic understanding of stress resistance in plant. In the present study, we identified differentially expressed genes (DEGs) in di-haploid Populus simonii × P. nigra under respective stresses of NaCl, KCl, CdCl2, and PEG. On the basis of RNA-Seq, we detected 247 DEGs that are shared by the four stresses in wild type poplar, and mRNA abundance of the DEGs were validated in transgenic poplar overexpressing ERF76 gene by RNA-Seq and RT-qPCR. Results from gene ontology analysis indicated that these genes are enriched in significant pathways, such as phenylpropanoid biosynthesis, phenylalanine metabolism, starch and sucrose metabolism, and plant hormone signal transduction. Ethylene response factor (ERF) gene family plays significant role in plant abiotic stress responses. We also investigated expression pattern of ERF gene family under the four stresses. The ERFs and DEGs share similar expression pattern across the four stresses. The transgenic poplar is superior to WT in morphologic, physiological and biochemical traits, which demonstrated the ERF76 gene plays a significant role in stress resistance. These studies will give a rise in understanding the stress response mechanisms in poplar. PMID:28265277

  3. Fragile X mental retardation protein (FMRP) interacting proteins exhibit different expression patterns during development.

    PubMed

    Bonaccorso, C M; Spatuzza, M; Di Marco, B; Gloria, A; Barrancotto, G; Cupo, A; Musumeci, S A; D'Antoni, S; Bardoni, B; Catania, M V

    2015-05-01

    Fragile X syndrome is caused by the lack of expression of fragile X mental retardation protein (FMRP), an RNA-binding protein involved in mRNA transport and translation. FMRP is a component of mRNA ribonucleoprotein complexes and it can interact with a range of proteins either directly or indirectly, as demonstrated by two-hybrid selection and co-immunoprecipitation, respectively. Most of FMRP-interacting proteins are RNA-binding proteins such as FXR1P, FXR2P and 82-FIP. Interestingly, FMRP can also interact directly with the cytoplasmic proteins CYFIP1 and CYFIP2, which do not bind RNA and link FMRP to the RhoGTPase pathway. The interaction with these different proteins may modulate the functions of FMRP by influencing its affinity to RNA and by affecting the FMRP ability of cytoskeleton remodeling through Rho/Rac GTPases. To better define the relationship of FMRP with its interacting proteins during brain development, we have analyzed the expression pattern of FMRP and its interacting proteins in the cortex, striatum, hippocampus and cerebellum at different ages in wild type (WT) mice. FMRP and FXR2P were strongly expressed during the first week and gradually decreased thereafter, more rapidly in the cerebellum than in the cortex. FXR1P was also expressed early and showed a reduction at later stages of development with a similar developmental pattern in these two regions. CYFIP1 was expressed at all ages and peaked in the third post-natal week. In contrast, CYFIP2 and 82-FIP (only in forebrain regions) were moderately expressed at P3 and gradually increased after P7. In general, the expression pattern of each protein was similar in the regions examined, except for 82-FIP, which exhibited a strong expression at P3 and low levels at later developmental stages in the cerebellum. Our data indicate that FMRP and its interacting proteins have distinct developmental patterns of expression and suggest that FMRP may be preferentially associated to certain proteins in

  4. Multispecies Analysis of Expression Pattern Diversification in the Recently Expanded Insect Ly6 Gene Family

    PubMed Central

    Tanaka, Kohtaro; Hazbun, Alexis; Hijazi, Assia; Vreede, Barbara; Sucena, Élio

    2015-01-01

    Gene families often consist of members with diverse expression domains reflecting their functions in a wide variety of tissues. However, how the expression of individual members, and thus their tissue-specific functions, diversified during the course of gene family expansion is not well understood. In this study, we approached this question through the analysis of the duplication history and transcriptional evolution of a rapidly expanding subfamily of insect Ly6 genes. We analyzed different insect genomes and identified seven Ly6 genes that have originated from a single ancestor through sequential duplication within the higher Diptera. We then determined how the original embryonic expression pattern of the founding gene diversified by characterizing its tissue-specific expression in the beetle Tribolium castaneum, the butterfly Bicyclus anynana, and the mosquito Anopheles stephensi and those of its duplicates in three higher dipteran species, representing various stages of the duplication history (Megaselia abdita, Ceratitis capitata, and Drosophila melanogaster). Our results revealed that frequent neofunctionalization episodes contributed to the increased expression breadth of this subfamily and that these events occurred after duplication and speciation events at comparable frequencies. In addition, at each duplication node, we consistently found asymmetric expression divergence. One paralog inherited most of the tissue-specificities of the founder gene, whereas the other paralog evolved drastically reduced expression domains. Our approach attests to the power of combining a well-established duplication history with a comprehensive coverage of representative species in acquiring unequivocal information about the dynamics of gene expression evolution in gene families. PMID:25743545

  5. Expression Pattern of Thyroid Hormone Transporters in the Postnatal Mouse Brain

    PubMed Central

    Müller, Julia; Heuer, Heike

    2014-01-01

    For a comprehensive description of the tissue-specific thyroidal state under normal as well as under pathophysiological conditions it is of utmost importance to include thyroid hormone (TH) transporters in the analysis as well. The current knowledge of the cell-specific repertoire of TH transporters, however, is still rather limited, although several TH transporting proteins have been identified. Here, we describe the temporal and spatial distribution pattern of the most prominent TH transporters in the postnatal mouse brain. For that purpose, we performed radioactive in situ hybridization studies in order to analyze the cellular mRNA expression pattern of the monocarboxylate transporters Mct8 and Mct10, the L-type amino acid transporters Lat1 and Lat2 as well as the organic anion transporting peptide Oatp1c1 at different postnatal time points. Highest TH transporter expression levels in the CNS were observed at postnatal day 6 and 12, while hybridization signal intensities visibly declined after the second postnatal week. The only exception was Mct10 for which the strongest signals could be observed in white matter regions at postnatal day 21 indicating that this transporter is preferentially expressed in mature oligodendrocytes. Whereas Mct8 and Lat2 showed an overlapping neuronal mRNA expression pattern in the cerebral cortex, hippocampus, and in the hypothalamus, Oatp1c1 and Lat1 specific signals were most prominent in capillary endothelial cells throughout the CNS. In the choroid plexus, expression of three transporters (Mct8, Lat2, and Oatp1c1) could be detected, whereas in other brain areas (e.g., striatum, thalamus, and brain stem nuclei) only one of the transporter candidates appeared to be present. Overall, our study revealed a distinct mRNA distribution pattern for each of the TH transporter candidates. Further studies will reveal to which extent these transporters contribute to the cell-specific TH uptake and efflux in the mouse CNS. PMID:24994998

  6. ceRNA crosstalk stabilizes protein expression and affects the correlation pattern of interacting proteins

    PubMed Central

    Martirosyan, Araks; De Martino, Andrea; Pagnani, Andrea; Marinari, Enzo

    2017-01-01

    Gene expression is a noisy process and several mechanisms, both transcriptional and post-transcriptional, can stabilize protein levels in cells. Much work has focused on the role of miRNAs, showing in particular that miRNA-mediated regulation can buffer expression noise for lowly expressed genes. Here, using in silico simulations and mathematical modeling, we demonstrate that miRNAs can exert a much broader influence on protein levels by orchestrating competition-induced crosstalk between mRNAs. Most notably, we find that miRNA-mediated cross-talk (i) can stabilize protein levels across the full range of gene expression rates, and (ii) modifies the correlation pattern of co-regulated interacting proteins, changing the sign of correlations from negative to positive. The latter feature may constitute a potentially robust signature of the existence of RNA crosstalk induced by endogenous competition for miRNAs in standard cellular conditions. PMID:28266541

  7. Differential evolution of MAGE genes based on expression pattern and selection pressure.

    PubMed

    Zhao, Qi; Caballero, Otavia L; Simpson, Andrew J G; Strausberg, Robert L

    2012-01-01

    Starting from publicly-accessible datasets, we have utilized comparative and phylogenetic genome analyses to characterize the evolution of the human MAGE gene family. Our characterization of genomic structures in representative genomes of primates, rodents, carnivora, and macroscelidea indicates that both Type I and Type II MAGE genes have undergone lineage-specific evolution. The restricted expression pattern in germ cells of Type I MAGE orthologs is observed throughout evolutionary history. Unlike Type II MAGEs that have conserved promoter sequences, Type I MAGEs lack promoter conservation, suggesting that epigenetic regulation is a central mechanism for controlling their expression. Codon analysis shows that Type I but not Type II MAGE genes have been under positive selection. The combination of genomic and expression analysis suggests that Type 1 MAGE promoters and genes continue to evolve in the hominin lineage, perhaps towards functional diversification or acquiring additional specific functions, and that selection pressure at codon level is associated with expression spectrum.

  8. ceRNA crosstalk stabilizes protein expression and affects the correlation pattern of interacting proteins.

    PubMed

    Martirosyan, Araks; De Martino, Andrea; Pagnani, Andrea; Marinari, Enzo

    2017-03-07

    Gene expression is a noisy process and several mechanisms, both transcriptional and post-transcriptional, can stabilize protein levels in cells. Much work has focused on the role of miRNAs, showing in particular that miRNA-mediated regulation can buffer expression noise for lowly expressed genes. Here, using in silico simulations and mathematical modeling, we demonstrate that miRNAs can exert a much broader influence on protein levels by orchestrating competition-induced crosstalk between mRNAs. Most notably, we find that miRNA-mediated cross-talk (i) can stabilize protein levels across the full range of gene expression rates, and (ii) modifies the correlation pattern of co-regulated interacting proteins, changing the sign of correlations from negative to positive. The latter feature may constitute a potentially robust signature of the existence of RNA crosstalk induced by endogenous competition for miRNAs in standard cellular conditions.

  9. Patterns of Hsp gene expression in ectothermic marine organisms on small to large biogeographic scales.

    PubMed

    Hofmann, Gretchen E

    2005-04-01

    The goal of my research program is to employ biochemical and molecular techniques to gain ecological insight into the role of temperature in setting species' distribution patterns in the marine environment. Our central focus is the study of the environmental regulation of gene expression, where we are particularly interested in a set of inducible molecular chaperones, the heat-shock proteins (Hsps), and how the expression of these genes varies with the thermal history of organisms in natural populations. The primary study organisms are intertidal invertebrates and marine fish that experience dramatic changes in body temperature on varying temporal and spatial scales. In this review, I present studies that address the variable expression of Hsps, how these genes are differentially regulated in ectothermic animals in response to ecologically relevant temperature conditions, and how such plasticity in gene expression contributes to physiological plasticity in the environment.

  10. Identification and expression pattern of the chemosensory protein gene family in the silkworm, Bombyx mori.

    PubMed

    Gong, Da-Ping; Zhang, Hui-Jie; Zhao, Ping; Lin, Ying; Xia, Qing-You; Xiang, Zhong-Huai

    2007-03-01

    Insect chemosensory proteins (CSPs) as well as odorant-binding proteins (OBPs) have been supposed to transport hydrophobic chemicals to receptors on sensory neurons. Compared with OBPs, CSPs are expressed more broadly in various insect tissues. We performed a genome-wide analysis of the candidate CSP gene family in the silkworm. A total of 20 candidate CSPs, including 3 gene fragments and 2 pseudogenes, were characterized based on their conserved cysteine residues and their similarity to CSPs in other insects. Some of these genes were clustered in the silkworm genome. The gene expression pattern of these candidates was investigated using RT-PCR and microarray, and the results showed that these genes were expressed primarily in mature larvae and the adult moth, suggesting silkworm CSPs may be involved in development. The majority of silkworm CSP genes are expressed broadly in tissues including the antennae, head, thorax, legs, wings, epithelium, testes, ovaries, pheromone glands, wing disks, and compound eyes.

  11. Differential Evolution of MAGE Genes Based on Expression Pattern and Selection Pressure

    PubMed Central

    Zhao, Qi; Caballero, Otavia L.; Simpson, Andrew J. G.; Strausberg, Robert L.

    2012-01-01

    Starting from publicly-accessible datasets, we have utilized comparative and phylogenetic genome analyses to characterize the evolution of the human MAGE gene family. Our characterization of genomic structures in representative genomes of primates, rodents, carnivora, and macroscelidea indicates that both Type I and Type II MAGE genes have undergone lineage-specific evolution. The restricted expression pattern in germ cells of Type I MAGE orthologs is observed throughout evolutionary history. Unlike Type II MAGEs that have conserved promoter sequences, Type I MAGEs lack promoter conservation, suggesting that epigenetic regulation is a central mechanism for controlling their expression. Codon analysis shows that Type I but not Type II MAGE genes have been under positive selection. The combination of genomic and expression analysis suggests that Type 1 MAGE promoters and genes continue to evolve in the hominin lineage, perhaps towards functional diversification or acquiring additional specific functions, and that selection pressure at codon level is associated with expression spectrum. PMID:23133577

  12. Distinguishing Marks of Simply-Connected Universes

    NASA Astrophysics Data System (ADS)

    Rebouças, M. J.; Dolgov, A.

    A statistical quantity suitable for distinguishing simply-connected Robertson-Walker (RW) universes is introduced, and its explicit expressions for the three possible classes of simply-connected RW universes with an uniform distribution of matter are determined. Graphs of the distinguishing mark for each class of RW universes are presented and analyzed. There sprout from our results an improvement on the procedure to extract the topological signature of multiply-connected RW universes, and a refined understanding of that topological signature of these universes studied in previous works.

  13. Altered pattern of cannabinoid type 1 receptor expression in adipose tissue of dysmetabolic and overweight patients.

    PubMed

    Sarzani, Riccardo; Bordicchia, Marica; Marcucci, Pierfrancesco; Bedetta, Samuele; Santini, Silvia; Giovagnoli, Andrea; Scappini, Lorena; Minardi, Daniele; Muzzonigro, Giovanni; Dessì-Fulgheri, Paolo; Rappelli, Alessandro

    2009-03-01

    In overweight patients (OW), the increased peripheral activity of the endocannabinoid system in visceral adipose tissue (VAT) may be mediated by cannabinoid type 1 (CB1) receptor expression. We determined whether CB1 receptor splice variants and messenger RNA (mRNA) levels in perirenal and subcutaneous adipose tissues are associated with obesity and metabolic syndrome (MetS). Gene expression with multiple-primers real-time polymerase chain reaction (TaqMan; Applied Biosystem, Weiterstadt, Germany) was performed to study VAT and paired subcutaneous adipose tissue (SAT) mRNA from 36 consecutive patients undergoing nephrectomy. Cannabinoid type 1A and CB1E mRNAs variants with the longer version of exon 4 were expressed. The CB1 expression in perirenal VAT significantly correlated with body mass index (BMI). Paired subcutaneous/perirenal samples from normal-weight patients (BMI < 25 kg/m(2)) showed higher CB1 expression in SAT (P = .002), whereas in OW (BMI > or = 25 kg/m(2)), the higher CB1 expression was in VAT (P = .038). In unpaired samples, SAT of normal-weight patients had significantly higher CB1 mRNA levels compared with SAT of OW, whereas higher CB1 expression (P = .009) was found in VAT of OW (n = 25). Overweight patients with increased visceral CB1 expression had higher waist circumference (P < .01), insulin (P < .01), and homeostasis model assessment index (P < .01). In addition, patients with the MetS (n = 22) showed higher CB1 expression in perirenal adipose tissues (P = .007). Visceral adipose CB1 expression correlated with BMI. Overweight patients and those with MetS showed a CB1 expression pattern supporting a CB1-mediated overactivity of the endocannabinoid system in human VAT.

  14. Gene expression patterns to define stages of post-harvest senescence in Alstroemeria petals.

    PubMed

    Breeze, Emily; Wagstaff, Carol; Harrison, Elizabeth; Bramke, Irene; Rogers, Hilary; Stead, Anthony; Thomas, Brian; Buchanan-Wollaston, Vicky

    2004-03-01

    Petal senescence in many species is regulated by ethylene but some flowers, such as those on the monocotyledonous plant Alstroemeria, var. Rebecca are ethylene insensitive. Changes in gene expression during the post-harvest senescence of Alstroemeria flowers were investigated using several different techniques. Suppressive subtractive hybridization (SSH) was used to obtain cDNA libraries enriched for genes expressed at selected stages of petal senescence. Sequencing of the EST clones obtained resulted in over 1000 sequences that represent approximately 500 different genes. Analysis of the potential functions of these genes provides a snapshot of the processes that are taking place during petal development. Both cell wall related genes and genes involved in metabolism were present at a higher proportion in the earlier stages. Genes encoding metal binding proteins (mostly metallothionein-like) were the major component of senescence enhanced libraries. This limited the diversity of genes identified showing differential expression at the later stages. Changes in the expression of all genes were analysed using microarray hybridization, and genes showing either up or down-regulation were identified. The expression pattern of a selection of genes was confirmed using Northern hybridization. Northern hybridization confirmed the up-regulation of metallothioneins after floral opening, however, this was not detected by the microarray analysis, indicating the importance of using a combination of methods to investigate gene expression patterns. Considerably more genes were up-regulated than down-regulated. This may reflect the need during Alstroemeria petal senescence for the expression of a whole new set of genes involved with degradation and mobilization. The potential uses of expression profiling to improve floral quality in breeding programmes or as a diagnostic tool are discussed.

  15. Early expressed genes showing a dichotomous developing pattern in the lancelet embryo.

    PubMed

    Yasui, K; Saiga, H; Wang, Y; Zhang, P J; Semba, I

    2001-04-01

    Lancelets (amphioxus), although showing the most similar anatomical features to vertebrates, never develop a vertebrate-like head but rather several structures specific to this animal. The lancelet anatomical specificity seems to be traceable to early developmental stages, such as the vertebrate dorsal and anterior-posterior determinations. The BMP and Wnt proteins play important roles in establishing the early basis of the dorsal structures and the head in vertebrates. The early behavior of BMP and Wnt may be also related to the specific body structures of lancelets. The expression patterns of a dpp-related gene, Bbbmp2/4, and two wnt-related genes, Bbwnt7 and Bbwnt8, have been studied in comparison with those of brachyury and Hnf-3beta class genes. The temporal expression patterns of these genes are similar to those of vertebrates; Bbbmp2/4 and Bbwnt8 are first expressed in the invaginating primitive gut and the equatorial region, respectively, at the initial gastrula stage. However, spatial expression pattern of Bbbmp2/4 differs significantly from the vertebrate cognates. It is expressed in the mid-dorsal inner layer of gastrulae and widely in the anterior region, in which vertebrates block BMP signaling. The present study suggests that the lancelet embryo may have two distinct developmental domains from the gastrula stage, the domains of which coincide later with the lateral diverticular and the somitocoelomic regions. The embryonic origin of the anterior-specific structures in lancelets corresponds to the anterior domain where Bbbmp2/4 is continuously expressed.

  16. Characterization, cDNA cloning and expression pattern of relaxin gene during embryogenesis of Danio rerio.

    PubMed

    Fiengo, Marcella; Donizetti, Aldo; del Gaudio, Rosanna; Minucci, Sergio; Aniello, Francesco

    2012-06-01

    We report the identification, the cDNA cloning, the temporal and spatial expression pattern analysis of the rln gene in the zebrafish Danio rerio. The deduced Rln B and A domains show different evolutionary conservation. Rln B domain shows higher similarity when compared to zebrafish and human RLN3 B domain than human RLN1 and RLN2 B domain. Differently, the zebrafish Rln A domain shows relatively low amino acid sequence similarity when compared with the same sequences. The rln gene is transcribed both during embryogenesis and in adult organism, where higher transcript level has been particularly evidenced in the brain. Moreover, we provide the first description of rln spatial expression pattern during embryonic development. In particular, we show restricted transcript localization starting at the pharyngula stage in olfactory placode, branchial arch region, and in a cell cluster near to otic vesicle. In larval stage, new transcription territories have been detected in both neural and non-neural regions. In particular, in the brain, rln expression has been revealed in telencephalic region around anterior commissure, in the preoptic area, and in restricted rombencephalic cell clusters. Expression of rln gene in extra-neural territories has been detected in the pancreatic and thyroid gland regions. Danio rerio rln expression pattern analysis reveals shared features with the mammalian RLN gene, particularly in the brain, where it might have a role in the neurophysiological processes. In addition, expression in the thyroid and pancreas region suggests a function as a paracrine and endocrine hormone. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

  17. Patterns of cytokeratin expression in monkey and human periodontium following regenerative and conventional periodontal surgery.

    PubMed

    Sculean, A; Berakdar, M; Pahl, S; Windisch, P; Brecx, M; Reich, E; Donos, N

    2001-08-01

    The pattern of cytokeratin expression has been extensively described in the normal and inflamed periodontium. However, there is no information regarding the pattern of cytokeratin expression in the periodontium which has been reformed following regenerative periodontal surgery. The aim of the present investigation was to evaluate the pattern of cytokeratin expression in the reformed human and monkey periodontium following regenerative and conventional periodontal surgery. In 3 monkeys, acute fenestration-type and chronic intrabony defects were treated with guided tissue regeneration (GTR), enamel matrix proteins (EMD), or coronally repositioned flap surgery (control). After a healing period of 5 months, the animals were sacrificed and perfused with 10% buffered formalin for fixation. Specimens containing the defects and surrounding tissues were dissected free, decalcified in EDTA and embedded in paraffin. Histological sections were cut with the microtome set at 3 microm. The sections were alternatively stained either with hematoxylin and eosin, or immunohistochemically by using one of the broad range monoclonal antibodies 34betaE 12 (for cytokeratins 1, 5, 10 and 14) or KL 1 (for cytokeratins 1, 2, 5, 6, 7, 8, 10, 11, 16 and 19), or one of the individual monoclonal antibodies LL025 (for cytokeratin 16), DC 10 (for cytokeratin 18), A53-B/A2 (for cytokeratin 19). Twelve patients, each displaying one deep intrabony defect scheduled for extraction due to advanced periodontitis or prosthetic reasons, were treated as described above. Following a healing period of 6 months, the teeth were extracted together with some of their surrounding soft and hard tissues. The histological and immunohistochemical processing of the human biopsies was identical to that described in monkeys. The results revealed that both the normal non-treated (original) monkey and human junctional epithelium stained strongly with all of the monoclonal antibodies used. The reformed junctional epithelium

  18. Repetitive sequence environment distinguishes housekeeping genes

    PubMed Central

    Eller, C. Daniel; Regelson, Moira; Merriman, Barry; Nelson, Stan; Horvath, Steve; Marahrens, York

    2007-01-01

    Housekeeping genes are expressed across a wide variety of tissues. Since repetitive sequences have been reported to influence the expression of individual genes, we employed a novel approach to determine whether housekeeping genes can be distinguished from tissue-specific genes their repetitive sequence context. We show that Alu elements are more highly concentrated around housekeeping genes while various longer (>400-bp) repetitive sequences ("repeats"), including Long Interspersed Nuclear Element 1 (LINE-1) elements, are excluded from these regions. We further show that isochore membership does not distinguish housekeeping genes from tissue-specific genes and that repetitive sequence environment distinguishes housekeeping genes from tissue-specific genes in every isochore. The distinct repetitive sequence environment, in combination with other previously published sequence properties of housekeeping genes, were used to develop a method of predicting housekeeping genes on the basis of DNA sequence alone. Using expression across tissue types as a measure of success, we demonstrate that repetitive sequence environment is by far the most important sequence feature identified to date for distinguishing housekeeping genes. PMID:17141428

  19. Regulation of Chlamydia Gene Expression by Tandem Promoters with Different Temporal Patterns.

    PubMed

    Rosario, Christopher J; Tan, Ming

    2015-11-02

    Chlamydia is a genus of pathogenic bacteria with an unusual intracellular developmental cycle marked by temporal waves of gene expression. The three main temporal groups of chlamydial genes are proposed to be controlled by separate mechanisms of transcriptional regulation. However, we have noted genes with discrepancies, such as the early gene dnaK and the midcycle genes bioY and pgk, which have promoters controlled by the late transcriptional regulators EUO and σ(28). To resolve this issue, we analyzed the promoters of these three genes in vitro and in Chlamydia trachomatis bacteria grown in cell culture. Transcripts from the σ(28)-dependent promoter of each gene were detected only at late times in the intracellular infection, bolstering the role of σ(28) RNA polymerase in late gene expression. In each case, however, expression prior to late times was due to a second promoter that was transcribed by σ(66) RNA polymerase, which is the major form of chlamydial polymerase. These results demonstrate that chlamydial genes can be transcribed from tandem promoters with different temporal profiles, leading to a composite expression pattern that differs from the expression profile of a single promoter. In addition, tandem promoters allow a gene to be regulated by multiple mechanisms of transcriptional regulation, such as DNA supercoiling or late regulation by EUO and σ(28). We discuss how tandem promoters broaden the repertoire of temporal gene expression patterns in the chlamydial developmental cycle and can be used to fine-tune the expression of specific genes. Chlamydia is a pathogenic bacterium that is responsible for the majority of infectious disease cases reported to the CDC each year. It causes an intracellular infection that is characterized by coordinated expression of chlamydial genes in temporal waves. Chlamydial transcription has been shown to be regulated by DNA supercoiling, alternative forms of RNA polymerase, and transcription factors, but the number

  20. Differential pattern of integrin receptor expression in differentiated and anaplastic thyroid cancer cell lines.

    PubMed

    Hoffmann, S; Maschuw, K; Hassan, I; Reckzeh, B; Wunderlich, A; Lingelbach, S; Zielke, A

    2005-09-01

    Adhesion of tumor cells to the extracellular matrix (ECM) is a crucial step for the development of metastatic disease and is mediated by specific integrin receptor molecules (IRM). The pattern of metastatic spread differs substantially among the various histotypes of thyroid cancer (TC). However, IRM have only occasionally been characterized in TC until now. IRM expression was investigated in 10 differentiated (FTC133, 236, 238, HTC, HTC TSHr, XTC, PTC4.0/4.2, TPC1, Kat5) and two anaplastic TC cell lines (ATC, C643, Hth74), primary cultures of normal thyroid tissue (Thy1,3), and thyroid cancer specimens (TCS). Expression of 16 IRM (beta1-4, beta7, alpha1-6, alphaV, alphaIIb, alphaL, alphaM, alphaX) and of four IRM heterodimers (alpha2beta1, alpha5beta1, alphaVbeta3, alphaVbeta5), was analyzed by fluorescent-activated cell sorter (FACS) and immunohistochemical staining. Thyroid tumor cell adhesion to ECM proteins and their IRM expression in response to thyrotropin (TSH) was assessed. Follicular TC cell lines presented high levels of integrins alpha2, alpha3, alpha5, beta1, beta3 and low levels of alpha1, whereas papillary lines expressed a heterogenous pattern of IRM, dominated by alpha5 and beta1. ATC mainly displayed integrins alpha2, alpha3, alpha5, alpha6, beta1 and low levels of alpha1, alpha4 and alphaV. Integrin heterodimers correlated with monomer expression. Evaluation of TCS largely confirmed these results with few exceptions, namely alpha4, alpha6, and beta3. The ability of TC cell lines to adhere to purified ECM proteins correlated with IRM expression. TSH induced TC cell adhesion in a dose-dependent fashion, despite an unchanged array of IRM expression or level of a particular IRM. Thyroid carcinoma cell lines of different histogenetic background display profoundly different patterns of IRM expression that appear to correlate with tumor aggressiveness. In vitro adhesion to ECM proteins and IRM expression concur. Finally, TSH-stimulated adhesion of

  1. Expression pattern of the homeotic gene Bapx1 during early chick gastrointestinal tract development.

    PubMed

    Faure, Sandrine; Georges, Maxime; McKey, Jennifer; Sagnol, Sébastien; de Santa Barbara, Pascal

    2013-12-01

    Regulation of the Bone Morphogenetic Protein (BMP) signaling pathway is essential for the normal development of vertebrate gastrointestinal (GI) tract, but also for the differentiation of the digestive mesenchymal layer into smooth muscles and submucosal layer. Different studies demonstrated that Bapx1 (for bagpipe homeobox homolog 1) negatively regulates the BMP pathway, but its precise expression pattern during the development and the differentiation of the GI tract mesenchyme actually remains to be examined. Here, we present the spatio-temporal expression profile of Bapx1 in the chick GI tract. We show that Bapx1 is first expressed in the undifferentiated mesenchyme of the gizzard and the colon. After the differentiation of the digestive mesenchyme, we found Bapx1 strongly expressed in the gizzard smooth muscle and in the submucosa layer of the colon. This expression pattern provides new insights into the roles of Bapx1 during the regionalization of the GI tract and the differentiation of the digestive mesenchyme of the colon and the stomach. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Ancient Out-of-Africa Mitochondrial DNA Variants Associate with Distinct Mitochondrial Gene Expression Patterns

    PubMed Central

    Mishmar, Dan

    2016-01-01

    Mitochondrial DNA (mtDNA) variants have been traditionally used as markers to trace ancient population migrations. Although experiments relying on model organisms and cytoplasmic hybrids, as well as disease association studies, have served to underline the functionality of certain mtDNA SNPs, only little is known of the regulatory impact of ancient mtDNA variants, especially in terms of gene expression. By analyzing RNA-seq data of 454 lymphoblast cell lines from the 1000 Genomes Project, we found that mtDNA variants defining the most common African genetic background, the L haplogroup, exhibit a distinct overall mtDNA gene expression pattern, which was independent of mtDNA copy numbers. Secondly, intra-population analysis revealed subtle, yet significant, expression differences in four tRNA genes. Strikingly, the more prominent African mtDNA gene expression pattern best correlated with the expression of nuclear DNA-encoded RNA-binding proteins, and with SNPs within the mitochondrial RNA-binding proteins PTCD1 and MRPS7. Our results thus support the concept of an ancient regulatory transition of mtDNA-encoded genes as humans left Africa to populate the rest of the world. PMID:27812116

  3. Long noncoding RNA expression patterns in lymph node metastasis in colorectal cancer by microarray.

    PubMed

    Rui, Qiang; Xu, Zipeng; Yang, Peng; He, Zhenyu

    2015-10-01

    To profile the long noncoding RNA (lncRNA) expression patterns in normal lymph node (NLN) of colorectal cancer compared with paired metastatic lymph node (MLN). MLN, NLN lncRNA and messenger RNA (mRNA) expression levels were determined by microarray in three patients; quantitative reverse transcription-polymerase chain reaction validation of 3 differentially expressed lncRNAs was conducted in another 26 patients. The lncRNAs' functions were predicted through coexpressed mRNA annotations. A total of 1133 lncRNA transcripts transcripts were dysregulated in metastatic lymph node, compared with normal lymph node. The expressions of the 3 chosen lncRNAs were validated by quantitative reverse transcription-polymerase chain reaction. Functional analysis suggests that several groups of lncRNAs may participate in biological pathways related to colorectal cancer by cis- and/or trans-regulation of protein-coding genes. This study constitutes the first report of lncRNA expression patterns in human MLN, NLN of colorectal cancer. More than 1000 dysregulated lncRNA transcripts are found by microarray. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. Patterning Expression of Regenerative Growth Factors Using High Intensity Focused Ultrasound

    PubMed Central

    Wilson, Christopher G.; Martín-Saavedra, Francisco M.; Padilla, Frédéric; Fabiilli, Mario L.; Zhang, Man; Baez, Alexander M.; Bonkowski, Christopher J.; Kripfgans, Oliver D.; Voellmy, Richard; Vilaboa, Nuria; Fowlkes, J. Brian

    2014-01-01

    Temporal and spatial control of growth factor gradients is critical for tissue patterning and differentiation. Reinitiation of this developmental program is also required for regeneration of tissues during wound healing and tissue regeneration. Devising methods for reconstituting growth factor gradients remains a central challenge in regenerative medicine. In the current study we develop a novel gene therapy approach for temporal and spatial control of two important growth factors in bone regeneration, vascular endothelial growth factor, and bone morphogenetic protein 2, which involves application of high intensity focused ultrasound to cells engineered with a heat-activated- and ligand-inducible gene switch. Induction of transgene expression was tightly localized within cell-scaffold constructs to subvolumes of ∼30 mm3, and the amplitude and projected area of transgene expression was tuned by the intensity and duration of ultrasound exposure. Conditions for ultrasound-activated transgene expression resulted in minimal cytotoxicity and scaffold damage. Localized regions of growth factor expression also established gradients in signaling activity, suggesting that patterns of growth factor expression generated by this method will have utility in basic and applied studies on tissue development and regeneration. PMID:24460731

  5. Specific patterns of changes in wheat gene expression after treatment with three antifungal compounds.

    PubMed

    Pasquer, Frédérique; Isidore, Edwige; Zarn, Jürg; Keller, Beat

    2005-03-01

    The two fungicides azoxystrobin and fenpropimorph are used against powdery mildew and rust diseases in wheat (Triticum aestivumL). Azoxystrobin, a strobilurin, inhibits fungal mitochondrial respiration and fenpropimorph, a morpholin, represses biosynthesis of ergosterol, the major sterol of fungal membranes. Although the fungitoxic activity of these compounds is well understood, their effects on plant metabolism remain unclear. In contrast to the fungicides which directly affect pathogen metabolism, benzo(1,2,3) thiadiazole-7-carbothioic acid S-methylester (BTH) induces resistance against wheat pathogens by the activation of systemic acquired resistance in the host plant. In this study, we monitored gene expression in spring wheat after treatment with each of these agrochemicals in a greenhouse trial using a microarray containing 600 barley cDNA clones. Defence-related genes were strongly induced after treatment with BTH, confirming the activation of a similar set of genes as in dicot plants following salicylic acid treatment. A similar gene expression pattern was observed after treatment with fenpropimorph and some defence-related genes were induced by azoxystrobin, demonstrating that these fungicides also activate a defence reaction. However, less intense responses were triggered than with BTH. The same experiments performed under field conditions gave dramatically different results. No gene showed differential expression after treatment and defence genes were already expressed at a high level before application of the agrochemicals. These differences in the expression patterns between the two environments demonstrate the importance of plant growth conditions for testing the impact of agrochemicals on plant metabolism.

  6. The embryonic expression patterns of zebrafish genes encoding LysM-domains.

    PubMed

    Laroche, F J F; Tulotta, C; Lamers, G E M; Meijer, A H; Yang, P; Verbeek, F J; Blaise, M; Stougaard, J; Spaink, H P

    2013-10-01

    The function and structure of LysM-domain containing proteins are very diverse. Although some LysM domains are able to bind peptidoglycan or chitin type carbohydrates in bacteria, in fungi and in plants, the function(s) of vertebrate LysM domains and proteins remains largely unknown. In this study we have identified and annotated the six zebrafish genes of this family, which encode at least ten conceptual LysM-domain containing proteins. Two distinct sub-families called LysMD and OXR were identified and shown to be highly conserved across vertebrates. The detailed characterization of LysMD and OXR gene expression in zebrafish embryos showed that all the members of these sub-families are strongly expressed maternally and zygotically from the earliest stages of a vertebrate embryonic development. Moreover, the analysis of the spatio-temporal expression patterns, by whole mount and fluorescent in situ hybridizations, demonstrates pronounced LysMD and OXR gene expression in the zebrafish brain and nervous system during stages of larval development. None of the zebrafish LysMD or OXR genes was responsive to challenge with bacterial pathogens in embryo models of Salmonella and Mycobacterium infections. In addition, the expression patterns of the OXR genes were mapped in a zebrafish brain atlas. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. NFI-C2 temporal-spatial expression and cellular localization pattern during tooth formation.

    PubMed

    Lamani, Ejvis; Gluhak-Heinrich, Jelica; MacDougall, Mary

    2015-12-01

    Currently, little is known regarding critical signaling pathways during later stages of tooth development, especially those associated with root formation. Nfi-c null mice, lacking molar roots, have implicated the transcription factor NFI-C as having an essential role in root development. Previously, we identified three NFI-C isoforms expressed in dental tissues with NFI-C2 being the major transcript. However, the expression pattern of the NFI-C2 protein is not characterized. In this study we performed in situ hybridization and immunohistochemistry using isoform specific probes. We show the production of a NFI-C2 peptide antibody, its characterization, the temporal-spatial expression pattern of the NFI-C2 protein during odontogenesis and sub-cellular localization in dental cells. Moderate NFI-C2 staining, as early as bud stage, was detected mostly in the condensing dental ectomesenchyme. This staining intensified within the dental pulp at later stages culminating in high expression in the dentin producing odontoblasts. The dental epithelium showed slight staining until cytodifferentiation of enamel organ into ameloblasts and stratum intermedium. During root formation NFI-C2 expression was high in the Hertwig's epithelial root sheath and later was found in the fully developed root and its supporting tissues. NFI-C2 cellular staining was cytosolic, associated with the Golgi, and nuclear. These data suggest a broader role for NFI-C during tooth formation than limited to root and periodontal ligament development. © 2015 Japanese Society of Developmental Biologists.

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

    PubMed Central

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

    2004-01-01

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

  9. The expression patterns of the clock genes period and timeless are affected by photoperiod in the Mediterranean corn stalk borer, Sesamia nonagrioides.

    PubMed

    Kontogiannatos, Dimitrios; Gkouvitsas, Theodoros; Kourti, Anna

    2017-01-01

    To obtain clues to the link between the molecular mechanism of circadian and photoperiod clocks, we cloned two circadian clock genes, period (per) and timeless (tim) from the moth Sesamia nonagrioides, which undergoes facultative diapause controlled by photoperiod. Sequence analysis revealed a high degree of conservation among the compared insects fοr both genes. We also investigated the expression patterns of per and tim in brains of larvae growing under 16L:8D (long days), constant darkness (DD) and 10L:14D (short days) conditions by qPCR assays. The results showed that mRNA accumulations encoding both genes exhibited diel oscillations under different photoperiods. The oscillation of per and tim mRNA, under short-day photoperiod differed from long-day. The difference between long-day and short-day conditions in the pattern of mRNA levels of per and tim appears to distinguish photoperiodic conditions clearly and both genes were influenced by photoperiod in different ways. We infer that not all photoperiodic clocks of insects interact with circadian clocks in the same fashion. Our results suggest that transcriptional regulations of the both clock genes act in the diapause programing in S. nonagrioides. The expression patterns of these genes are affected by photoperiod but runs with 24 h by entrainment to daily environmental cues.

  10. Phylogeny, expression patterns and regulation of DNA Methyltransferases in early development of the flatfish, Solea senegalensis.

    PubMed

    Firmino, Joana; Carballo, Carlos; Armesto, Paula; Campinho, Marco A; Power, Deborah M; Manchado, Manuel

    2017-07-17

    The identification of DNA methyltransferases (Dnmt) expression patterns during development and their regulation is important to understand the epigenetic mechanisms that modulate larval plasticity in marine fish. In this study, dnmt1 and dnmt3 paralogs were identified in the flatfish Solea senegalensis and expression patterns in early developmental stages and juveniles were determined. Additionally, the regulation of Dnmt transcription by a specific inhibitor (5-aza-2'-deoxycytidine) and temperature was evaluated. Five paralog genes of dnmt3, namely dnmt3aa, dnmt3ab, dnmt3ba, dnmt3bb.1 and dnmt3bb.2 and one gene for dnmt1 were identified. Phylogenetic analysis revealed that the dnmt gene family was highly conserved in teleosts and three fish-specific genes, dnmt3aa, dnmt3ba and dnmt3bb.2 have evolved. The spatio-temporal expression patterns of four dnmts (dnmt1, dnmt3aa, dnmt3ab and dnmt3bb.1) were different in early larval stages although all of them reduced expression with the age and were detected in neural organs and dnmt3aa appeared specific to somites. In juveniles, the four dnmt genes were expressed in brain and hematopoietic tissues such as kidney, spleen and gills. Treatment of sole embryos with 5-aza-2'-deoxycytidine down-regulated dntm1 and up-regulated dntm3aa. Moreover, in lecithotrophic larval stages, dnmt3aa and dnmt3ab were temperature sensitive and their expression was higher in larvae incubated at 16 °C relative to 20 °C. Five dnmt3 and one dnmt1 paralog were identified in sole and their distinct developmental and tissue-specific expression patterns indicate that they may have different roles during development. The inhibitor 5-aza-2'-deoxycytidine modified the transcript abundance of dntm1 and dntm3aa in embryos, which suggests that a regulatory feedback mechanism exists for these genes. The impact of thermal regime on expression levels of dnmt3aa and dnmt3ab in lecithotrophic larval stages suggests that these paralogs might be involved in

  11. Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer.

    PubMed

    Budinska, Eva; Popovici, Vlad; Tejpar, Sabine; D'Ario, Giovanni; Lapique, Nicolas; Sikora, Katarzyna Otylia; Di Narzo, Antonio Fabio; Yan, Pu; Hodgson, John Graeme; Weinrich, Scott; Bosman, Fred; Roth, Arnaud; Delorenzi, Mauro

    2013-09-01

    The recognition that colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behaviour and response to therapy translates into an urgent need for robust molecular disease subclassifiers that can explain this heterogeneity beyond current parameters (MSI, KRAS, BRAF). Attempts to fill this gap are emerging. The Cancer Genome Atlas (TGCA) reported two main CRC groups, based on the incidence and spectrum of mutated genes, and another paper reported an EMT expression signature defined subgroup. We performed a prior free analysis of CRC heterogeneity on 1113 CRC gene expression profiles and confronted our findings to established molecular determinants and clinical, histopathological and survival data. Unsupervised clustering based on gene modules allowed us to distinguish at least five different gene expression CRC subtypes, which we call surface crypt-like, lower crypt-like, CIMP-H-like, mesenchymal and mixed. A gene set enrichment analysis combined with literature search of gene module members identified distinct biological motifs in different subtypes. The subtypes, which were not derived based on outcome, nonetheless showed differences in prognosis. Known gene copy number variations and mutations in key cancer-associated genes differed between subtypes, but the subtypes provided molecular information beyond that contained in these variables. Morphological features significantly differed between subtypes. The objective existence of the subtypes and their clinical and molecular characteristics were validated in an independent set of 720 CRC expression profiles. Our subtypes provide a novel perspective on the heterogeneity of CRC. The proposed subtypes should be further explored retrospectively on existing clinical trial datasets and, when sufficiently robust, be prospectively assessed for clinical relevance in terms of prognosis and treatment response predictive capacity. Original microarray data were uploaded to the ArrayExpress database (http

  12. Gene expression patterns in rainbow trout, Oncorhynchus mykiss, exposed to a suite of model toxicants.

    PubMed

    Hook, Sharon E; Skillman, Ann D; Small, Jack A; Schultz, Irvin R

    2006-05-25

    The increased availability and use of DNA microarrays has allowed the characterization of gene expression patterns associated with exposure to different toxicants. An important question is whether toxicant induced changes in gene expression in fish are sufficiently diverse to allow for identification of specific modes of action and/or specific contaminants. In theory, each class of toxicant may generate a gene expression profile unique to its mode of toxic action. In this study, isogenic (cloned) rainbow trout Oncorhynchus mykiss were exposed to sublethal levels of a series of model toxicants with varying modes of action, including ethynylestradiol (xeno-estrogen), 2,2,4,4'-tetrabromodiphenyl ether (BDE-47, thyroid active), diquat (oxidant stressor), chromium VI, and benzo[a]pyrene (BaP) for a period of 1-3 weeks. An additional experiment measured trenbolone (anabolic steroid; model androgen) induced gene expression changes in sexually mature female trout. Following exposure, fish were euthanized, livers removed and RNA extracted. Fluorescently labeled cDNA were generated and hybridized against a commercially available Atlantic Salmon/Trout array (GRASP project, University of Victoria) spotted with 16,000 cDNA's. The slides were scanned to measure abundance of a given transcript in each sample relative to controls. Data were analyzed via Genespring (Silicon Genetics) to identify a list of up- and downregulated genes, as well as to determine gene clustering patterns that can be used as "expression signatures". The results indicate each toxicant exposure caused between 64 and 222 genes to be significantly altered in expression. Most genes exhibiting altered expression responded to only one of the toxicants and relatively few were co-expressed in multiple treatments. For example, BaP and Diquat, both of which exert toxicity via oxidative stress, upregulated 28 of the same genes, of over 100 genes altered by either treatment. Other genes associated with steroidogenesis

  13. Gene expression patterns in rainbow trout, Oncorhynchus mykiss, exposed to a suite of model toxicants

    PubMed Central

    Hook, Sharon E.; Skillman, Ann D.; Small, Jack A.; Schultz, Irvin R.

    2008-01-01

    The increased availability and use of DNA microarrays has allowed the characterization of gene expression patterns associated with exposure to different toxicants. An important question is whether toxicant induced changes in gene expression in fish are sufficiently diverse to allow for identification of specific modes of action and/or specific contaminants. In theory, each class of toxicant may generate a gene expression profile unique to its mode of toxic action. In this study, isogenic (cloned) rainbow trout Oncorhynchus mykiss were exposed to sublethal levels of a series of model toxicants with varying modes of action, including ethynylestradiol (xeno-estrogen), 2,2,4,4′-tetrabromodiphenyl ether (BDE-47, thyroid active), diquat (oxidant stressor), chromium VI, and benzo[a]pyrene (BaP) for a period of 1–3 weeks. An additional experiment measured trenbolone (anabolic steroid; model androgen) induced gene expression changes in sexually mature female trout. Following exposure, fish were euthanized, livers removed and RNA extracted. Fluorescently labeled cDNA were generated and hybridized against a commercially available Atlantic Salmon/Trout array (GRASP project, University of Victoria) spotted with 16,000 cDNA’s. The slides were scanned to measure abundance of a given transcript in each sample relative to controls. Data were analyzed via Genespring (Silicon Genetics) to identify a list of up- and downregulated genes, as well as to determine gene clustering patterns that can be used as “expression signatures”. The results indicate each toxicant exposure caused between 64 and 222 genes to be significantly altered in expression. Most genes exhibiting altered expression responded to only one of the toxicants and relatively few were co-expressed in multiple treatments. For example, BaP and Diquat, both of which exert toxicity via oxidative stress, upregulated 28 of the same genes, of over 100 genes altered by either treatment. Other genes associated with

  14. Wnt repertoire and developmental expression patterns in the crustacean Thamnocephalus platyurus.

    PubMed

    Constantinou, Savvas J; Pace, Ryan M; Stangl, A J; Nagy, Lisa M; Williams, Terri A

    2016-12-01

    Wnt genes are a family of conserved glycoprotein ligands that play a role in a wide variety of cell and developmental processes, from cell proliferation to axis elongation. There are 13 Wnt subfamilies found among metazoans. Eleven of these appear conserved in arthropods with a pattern of loss during evolution of as many as six subfamilies among hexapods. Here we report on Wnt genes in the branchiopod crustacean, Thamnocephalus platyurus, including the first documentation of the expression of the complete Wnt gene family in a crustacean. Our results suggest fewer Wnt genes were retained in Thamnocephalus than in the related crustacean, Daphnia, although the Thamnocephalus Wnt repertoire is larger than that found in insects. We also find an intriguing pattern of staggered expression of Wnts-an anterior-posterior stagger within the posterior growth zone and a dorsal-ventral stagger in the developing segments-suggesting a potential for subfunctionalization of Wnts in these regions. © 2016 Wiley Periodicals, Inc.

  15. Different expression patterns of Lin28 and Lin28b in mouse molar development.

    PubMed

    Dong, Ning; Liu, Yan; Zhang, Tiantian; Zhao, Lin; Tian, Jiangang; Ruan, Jianping

    2017-10-01

    The RNA-binding proteins Lin28 and Lin28b are expressed in many developing tissues and are involved in the biosynthesis of the microRNA let-7 family and embryogenesis processes. However, their roles in mammalian tooth development remain ill-defined. The spatiotemporal expressions of Lin28 and Lin28b during mouse molar odontogenesis from day E11.5 to P21 were examined through immunohistochemistry and western blot analysis. Both Lin28 and Lin28b were initially expressed in dental epithelium, but the expression patterns varied thereafter. Lin28 was expressed in tooth germ from early embryonic stages and was consistently expressed in the ameloblasts and odontoblasts throughout all stages of tooth development. However, positive staining of Lin28b gradually faded out with tooth germ development, before finally disappearing in tooth organ cells after birth. These results indicate that Lin28 was spatiotemporally expressed in tooth germ throughout tooth development progression and may play an active role in ameloblast and odontoblast differentiation, as well as matrix secretion and the mineralization of enamel and dentin. Its paralogue Lin28b may have a distinct function in tooth germ formation. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2016-01-01

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

  17. Expression patterns of gdnf and gfrα1 in rainbow trout testis.

    PubMed

    Nakajima, Satoshi; Hayashi, Makoto; Kouguchi, Tomomi; Yamaguchi, Kazuma; Miwa, Misako; Yoshizaki, Goro

    2014-03-01

    In mice, glial cell line-derived neurotrophic factor (GDNF) is essential for normal spermatogenesis and in vitro culture of spermatogonial stem cells. In murine testes, GDNF acts as paracrine factor; Sertoli cells secrete it to a subset of spermatogonial cells expressing its receptor, GDNF family receptor α1 (GFRα1). However, in fish, it is unclear what types of cells express gdnf and gfrα1. In this study, we isolated the rainbow trout orthologues of these genes and analyzed their expression patterns during spermatogenesis. In rainbow trout testes, gdnf and gfrα1 were expressed in almost all type A spermatogonia (ASG). Noticeably, unlike in mice, the expression of gdnf was not observed in Sertoli cells in rainbow trout. During spermatogenesis, the expression levels of these genes changed synchronously; gdnf and gfrα1 showed high expression in ASG and decreased dramatically in subsequent developmental stages. These results suggested that GDNF most likely acts as an autocrine factor in rainbow trout testes. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Distinct regulatory elements mediate similar expression patterns in the excretory cell of Caenorhabditis elegans.

    PubMed

    Zhao, Zhongying; Fang, Li; Chen, Nansheng; Johnsen, Robert C; Stein, Lincoln; Baillie, David L

    2005-11-18

    Identification of cis-regulatory elements and their binding proteins constitutes an important part of understanding gene function and regulation. It is well accepted that co-expressed genes tend to share transcriptional elements. However, recent findings indicate that co-expression data show poor correlation with co-regulation data even in unicellular yeast. This motivates us to experimentally explore whether it is possible that co-expressed genes are subject to differential regulatory control using the excretory cell of Caenorhabditis elegans as an example. Excretory cell is a functional equivalent of human kidney. Transcriptional regulation of gene expression in the cell is largely unknown. We isolated a 10-bp excretory cell-specific cis-element, Ex-1, from a pgp-12 promoter. The significance of the element has been demonstrated by its capacity of converting an intestine-specific promoter into an excretory cell-specific one. We also isolated a cDNA encoding an Ex-1 binding transcription factor, DCP-66, using a yeast one-hybrid screen. Role of the factor in regulation of pgp-12 expression has been demonstrated both in vitro and in vivo. Search for occurrence of Ex-1 reveals that only a small portion of excretory cell-specific promoters contain Ex-1. Two other distinct cis-elements isolated from two different promoters can also dictate the excretory cell-specific expression but are independent of regulation by DCP-66. The results indicate that distinct regulatory elements are able to mediate the similar expression patterns.

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

    PubMed

    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.

  20. Differential expression patterns of metastasis suppressor proteins in basal cell carcinoma.

    PubMed

    Bozdogan, Onder; Yulug, Isik G; Vargel, Ibrahim; Cavusoglu, Tarik; Karabulut, Ayse A; Karahan, Gurbet; Sayar, Nilufer

    2015-08-01

    Basal cell carcinomas (BCCs) are common malignant skin tumors. Despite having a significant invasion capacity, they metastasize only rarely. Our aim in this study was to detect the expression patterns of the NM23-H1, NDRG1, E-cadherin, RHOGDI2, CD82/KAI1, MKK4, and AKAP12 metastasis suppressor proteins in BCCs. A total of 96 BCC and 10 normal skin samples were included for the immunohistochemical study. Eleven frozen BCC samples were also studied by quantitative real time polymerase chain reaction (qRT-PCR) to detect the gene expression profile. NM23-H1 was strongly and diffusely expressed in all types of BCC. Significant cytoplasmic expression of NDRG1 and E-cadherin was also detected. However, AKAP12 and CD82/KAI1 expression was significantly decreased. The expressions of the other proteins were somewhere between the two extremes. Similarly, qRT-PCR analysis showed down-regulation of AKAP12 and up-regulation of NM23-H1 and NDRG1 in BCC. Morphologically aggressive BCCs showed significantly higher cytoplasmic NDRG1 expression scores and lower CD82/KAI1 scores than non-aggressive BCCs. The relatively preserved levels of NM23-H1, NDRG1, and E-cadherin proteins may have a positive effect on the non-metastasizing features of these tumors. © 2014 The International Society of Dermatology.

  1. Oncogenic relevant defensins: expression pattern and proliferation characteristics of human tumor cell lines.

    PubMed

    Winter, Jochen; Kraus, Dominik; Reckenbeil, Jan; Probstmeier, Rainer

    2016-06-01

    The objective of this study was to investigate gene expression levels of oncogenic relevant human defensins and their impact on proliferation rates of 29 cell lines derived from main types of different tumor origins. Differential gene expression analysis of human defensins was performed by real-time PCR experiments. The proliferation rate of tumor cells that had been cultivated in the absence or presence of biologically active peptides was analyzed with a lactate dehydrogenase assay kit. At least one member of the defensin family was expressed in each tumor cell line, whereby α-defensin (DEFA1), DEFA2, or DEFA3 transcripts could be ubiquitously detected. Cell lines of neural origin (glioma, neuroblastoma, and small-cell lung carcinoma) expressed far less human β-defensins (hBDs) in comparison to other tumor types. The expression level of a specific defensin in various cell lines could vary by more than five orders of magnitude. Compensatory mechanisms on the expression levels of the different defensins could not be strictly observed. Only in 3 out of 29 tumor cell lines the proliferation rate was affected after defensin stimulation. The variable appearance of defensins, as well as the cell line-restricted functional activity, argues for the integration of defensins in complex cellular and molecular networks that tolerate rather flexible expression patterns.

  2. Distinctive expression patterns of glycoprotein non-metastatic B and folliculin in renal tumors in patients with Birt-Hogg-Dubé syndrome.

    PubMed

    Furuya, Mitsuko; Hong, Seung-Beom; Tanaka, Reiko; Kuroda, Naoto; Nagashima, Yoji; Nagahama, Kiyotaka; Suyama, Takahito; Yao, Masahiro; Nakatani, Yukio

    2015-03-01

    Birt-Hogg-Dubé syndrome (BHD) is an inherited disorder associated with a germline mutation of the folliculin gene (FLCN). The affected families have a high risk for developing multiple renal cell carcinomas (RCC). Diagnostic markers that distinguish between FLCN-related RCC and sporadic RCC have not been investigated, and many patients with undiagnosed BHD fail to receive proper medical care. We investigated the histopathology of 27 RCCs obtained from 18 BHD patients who were diagnosed by genetic testing. Possible somatic mutations of RCC lesions were investigated by DNA sequencing. Western blotting and immunohistochemical staining were used to compare the expression levels of FLCN and glycoprotein non-metastatic B (GPNMB) between FLCN-related RCCs and sporadic renal tumors (n = 62). The expression of GPNMB was also evaluated by quantitative RT-PCR. Histopathological analysis revealed that the most frequent histological type was chromophobe RCC (n = 12), followed by hybrid oncocytic/chromophobe tumor (n = 6). Somatic mutation analysis revealed small intragenic mutations in six cases and loss of heterozygosity in two cases. Western blot and immunostaining analyses revealed that FLCN-related RCCs showed overexpression of GPNMB and underexpression of FLCN, whereas sporadic tumors showed inverted patterns. GPNMB mRNA in FLCN-related RCCs was 23-fold more abundant than in sporadic tumors. The distinctive expression patterns of GPNMB and FLCN might identify patients with RCCs who need further work-up for BHD.

  3. Distinctive expression patterns of glycoprotein non-metastatic B and folliculin in renal tumors in patients with Birt–Hogg–Dubé syndrome

    PubMed Central

    Furuya, Mitsuko; Hong, Seung-Beom; Tanaka, Reiko; Kuroda, Naoto; Nagashima, Yoji; Nagahama, Kiyotaka; Suyama, Takahito; Yao, Masahiro; Nakatani, Yukio

    2015-01-01

    Birt–Hogg–Dubé syndrome (BHD) is an inherited disorder associated with a germline mutation of the folliculin gene (FLCN). The affected families have a high risk for developing multiple renal cell carcinomas (RCC). Diagnostic markers that distinguish between FLCN-related RCC and sporadic RCC have not been investigated, and many patients with undiagnosed BHD fail to receive proper medical care. We investigated the histopathology of 27 RCCs obtained from 18 BHD patients who were diagnosed by genetic testing. Possible somatic mutations of RCC lesions were investigated by DNA sequencing. Western blotting and immunohistochemical staining were used to compare the expression levels of FLCN and glycoprotein non-metastatic B (GPNMB) between FLCN-related RCCs and sporadic renal tumors (n = 62). The expression of GPNMB was also evaluated by quantitative RT-PCR. Histopathological analysis revealed that the most frequent histological type was chromophobe RCC (n = 12), followed by hybrid oncocytic/chromophobe tumor (n = 6). Somatic mutation analysis revealed small intragenic mutations in six cases and loss of heterozygosity in two cases. Western blot and immunostaining analyses revealed that FLCN-related RCCs showed overexpression of GPNMB and underexpression of FLCN, whereas sporadic tumors showed inverted patterns. GPNMB mRNA in FLCN-related RCCs was 23-fold more abundant than in sporadic tumors. The distinctive expression patterns of GPNMB and FLCN might identify patients with RCCs who need further work-up for BHD. PMID:25594584

  4. Chronic maternal morphine alters calbindin D-28k expression pattern in postnatal mouse brain.

    PubMed

    Mithbaokar, Pratibha; Fiorito, Filomena; Della Morte, Rossella; Maharajan, Veeramani; Costagliola, Anna

    2016-01-01

    The distribution pattern of calbindin (CB)-D28k-expressing neurons results to be altered in several brain regions of chronic morphine exposed adult mice. In this study, the influence of chronic maternal exposure to morphine on the distribution pattern of CB-D28k-expressing neurons in the brain of mouse offspring was investigated. Females of CD-1 mice were daily administered with saline or morphine for 7 days before mating, during the whole gestation period, and until 21 day post-partum. Their offspring were sacrificed on postnatal day 18, and the brains were examined by histology using cresyl violet and by immunohistochemistry using a rabbit polyclonal anti-CB-D28k antibody. Histology revealed no significant differences in the distribution pattern and the number of neurons between the offspring forebrain of the control group of mice and the two groups of mice treated with different doses of morphine. However, immunohistochemical analysis revealed that the number of CB-D28k-immunoreactive neurons remarkably decreased in the cingulate cortex, in the layers II-IV of the parietal cortex and in all regions of the hippocampus, while it increased in the layers V-VI of the parietal cortex and in the subicular region of the offspring brain of morphine treated mice. Overall, our findings demonstrate that maternal exposure to morphine alters the pattern of CB-D28k-expressing neuron pattern in specific regions of murine developing brain, in a layer- and dose-dependent way, thus suggesting that these alterations might represent a mechanism by which morphine modifies the functional aspects of developing brain.

  5. Differential gene expression patterns between smokers and non-smokers: cause or consequence?

    PubMed

    Vink, Jacqueline M; Jansen, Rick; Brooks, Andy; Willemsen, Gonneke; van Grootheest, Gerard; de Geus, Eco; Smit, Jan H; Penninx, Brenda W; Boomsma, Dorret I

    2017-03-01

    The molecular mechanisms causing smoking-induced health decline are largely unknown. To elucidate the molecular pathways involved in cause and consequences of smoking behavior, we conducted a genome-wide gene expression study in peripheral blood samples targeting 18 238 genes. Data of 743 smokers, 1686 never smokers and 890 ex-smokers were available from two population-based cohorts from the Netherlands. In addition, data of 56 monozygotic twin pairs discordant for ever smoking were used. One hundred thirty-two genes were differentially expressed between current smokers and never smokers (P < 1.2 × 10(-6) , Bonferroni correction). The most significant genes were G protein-coupled receptor 15 (P < 1 × 10(-150) ) and leucine-rich repeat neuronal 3 (P < 1 × 10(-44) ). The smoking-related genes were enriched for immune system, blood coagulation, natural killer cell and cancer pathways. By taking the data of ex-smokers into account, expression of these 132 genes was classified into reversible (94 genes), slowly reversible (31 genes), irreversible (6 genes) or inconclusive (1 gene). Expression of 6 of the 132 genes (three reversible and three slowly reversible) was confirmed to be reactive to smoking as they were differentially expressed in monozygotic pairs discordant for smoking. Cis-expression quantitative trait loci for GPR56 and RARRES3 (downregulated in smokers) were associated with increased number of cigarettes smoked per day in a large genome-wide association meta-analysis, suggesting a causative effect of GPR56 and RARRES3 expression on smoking behavior. In conclusion, differential gene expression patterns in smokers are extensive and cluster in several underlying disease pathways. Gene expression differences seem mainly direct consequences of smoking, and largely reversible after smoking cessation. However, we also identified DNA variants that may influence smoking behavior via the mediating gene expression.

  6. Differential gene expression patterns between smokers and non‐smokers: cause or consequence?

    PubMed Central

    Jansen, Rick; Brooks, Andy; Willemsen, Gonneke; van Grootheest, Gerard; de Geus, Eco; Smit, Jan H.; Penninx, Brenda W.; Boomsma, Dorret I.

    2015-01-01

    Abstract The molecular mechanisms causing smoking‐induced health decline are largely unknown. To elucidate the molecular pathways involved in cause and consequences of smoking behavior, we conducted a genome‐wide gene expression study in peripheral blood samples targeting 18 238 genes. Data of 743 smokers, 1686 never smokers and 890 ex‐smokers were available from two population‐based cohorts from the Netherlands. In addition, data of 56 monozygotic twin pairs discordant for ever smoking were used. One hundred thirty‐two genes were differentially expressed between current smokers and never smokers (P < 1.2 × 10−6, Bonferroni correction). The most significant genes were G protein‐coupled receptor 15 (P < 1 × 10−150) and leucine‐rich repeat neuronal 3 (P < 1 × 10−44). The smoking‐related genes were enriched for immune system, blood coagulation, natural killer cell and cancer pathways. By taking the data of ex‐smokers into account, expression of these 132 genes was classified into reversible (94 genes), slowly reversible (31 genes), irreversible (6 genes) or inconclusive (1 gene). Expression of 6 of the 132 genes (three reversible and three slowly reversible) was confirmed to be reactive to smoking as they were differentially expressed in monozygotic pairs discordant for smoking. Cis‐expression quantitative trait loci for GPR56 and RARRES3 (downregulated in smokers) were associated with increased number of cigarettes smoked per day in a large genome‐wide association meta‐analysis, suggesting a causative effect of GPR56 and RARRES3 expression on smoking behavior. In conclusion, differential gene expression patterns in smokers are extensive and cluster in several underlying disease pathways. Gene expression differences seem mainly direct consequences of smoking, and largely reversible after smoking cessation. However, we also identified DNA variants that may influence smoking behavior via the mediating gene

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

    SciTech Connect

    Pandi, Narayanan Sathiya Suganya, Sivagurunathan; Rajendran, Suriliyandi

    2013-10-04

    Highlights: •Identified stomach lineage specific gene set (SLSGS) was found to be under expressed in gastric tumors. •Elevated expression of SLSGS in gastric tumor is a molecular predictor of metabolic type gastric cancer. •In silico pathway scanning identified estrogen-α signaling is a putative regulator of SLSGS in gastric cancer. •Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. -- Abstract: 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.

  8. Dogs Evaluate Threatening Facial Expressions by Their Biological Validity--Evidence from Gazing Patterns.

    PubMed

    Somppi, Sanni; Törnqvist, Heini; Kujala, Miiamaaria V; Hänninen, Laura; Krause, Christina M; Vainio, Outi

    2016-01-01

    Appropriate response to companions' emotional signals is important for all social creatures. The emotional expressions of humans and non-human animals have analogies in their form and function, suggesting shared evolutionary roots, but very little is known about how animals other than primates view and process facial expressions. In primates, threat-related facial expressions evoke exceptional viewing patterns compared with neutral or positive stimuli. Here, we explore if domestic dogs (Canis familiaris) have such an attentional bias toward threatening social stimuli and whether observed emotional expressions affect dogs' gaze fixation distribution among the facial features (eyes, midface and mouth). We recorded the voluntary eye gaze of 31 domestic dogs during viewing of facial photographs of humans and dogs with three emotional expressions (threatening, pleasant and neutral). We found that dogs' gaze fixations spread systematically among facial features. The distribution of fixations was altered by the seen expression, but eyes were the most probable targets of the first fixations and gathered longer looking durations than mouth regardless of the viewed expression. The examination of the inner facial features as a whole revealed more pronounced scanning differences among expressions. This suggests that dogs do not base their perception of facial expressions on the viewing of single structures, but the interpretation of the composition formed by eyes, midface and mouth. Dogs evaluated social threat rapidly and this evaluation led to attentional bias, which was dependent on the depicted species: threatening conspecifics' faces evoked heightened attention but threatening human faces instead an avoidance response. We propose that threatening signals carrying differential biological validity are processed via distinctive neurocognitive pathways. Both of these mechanisms may have an adaptive significance for domestic dogs. The findings provide a novel perspective on

  9. Dogs Evaluate Threatening Facial Expressions by Their Biological Validity – Evidence from Gazing Patterns

    PubMed Central

    Somppi, Sanni; Törnqvist, Heini; Kujala, Miiamaaria V.; Hänninen, Lau