Translating Mendelian and complex inheritance of Alzheimer's disease genes for predicting unique personal genome variants

PubMed Central

Regan, Kelly; Wang, Kanix; Doughty, Emily; Li, Haiquan; Li, Jianrong; Lee, Younghee; Kann, Maricel G

2012-01-01

Objective Although trait-associated genes identified as complex versus single-gene inheritance differ substantially in odds ratio, the authors nonetheless posit that their mechanistic concordance can reveal fundamental properties of the genetic architecture, allowing the automated interpretation of unique polymorphisms within a personal genome. Materials and methods An analytical method, SPADE-gen, spanning three biological scales was developed to demonstrate the mechanistic concordance between Mendelian and complex inheritance of Alzheimer's disease (AD) genes: biological functions (BP), protein interaction modeling, and protein domain implicated in the disease-associated polymorphism. Results Among Gene Ontology (GO) biological processes (BP) enriched at a false detection rate <5% in 15 AD genes of Mendelian inheritance (Online Mendelian Inheritance in Man) and independently in those of complex inheritance (25 host genes of intragenic AD single-nucleotide polymorphisms confirmed in genome-wide association studies), 16 overlapped (empirical p=0.007) and 45 were similar (empirical p<0.009; information theory). SPAN network modeling extended the canonical pathway of AD (KEGG) with 26 new protein interactions (empirical p<0.0001). Discussion The study prioritized new AD-associated biological mechanisms and focused the analysis on previously unreported interactions associated with the biological processes of polymorphisms that affect specific protein domains within characterized AD genes and their direct interactors using (1) concordant GO-BP and (2) domain interactions within STRING protein–protein interactions corresponding to the genomic location of the AD polymorphism (eg, EPHA1, APOE, and CD2AP). Conclusion These results are in line with unique-event polymorphism theory, indicating how disease-associated polymorphisms of Mendelian or complex inheritance relate genetically to those observed as ‘unique personal variants’. They also provide insight for

Functional analysis of two polygalacturonase genes in Apolygus lucorum associated with eliciting plant injury using RNA interference.

PubMed

Zhang, Wanna; Liu, Bing; Lu, Yanhui; Liang, Gemei

2017-04-01

Salivary enzymes of many piercing-sucking insects lead to host plant injury. The salivary enzymes, polygalacturonase (PGs), act in insect feeding. PG family genes have been cloned from the mirid bug Apolygus lucorum, a pest of cotton and other host crops in China. We investigated the function of two PG genes that are highly expressed in A. lucorum nymphs (PG3-4) and adults (PG3-5), using siRNA injection-based RNA interference (RNAi). Accumulation of mRNA encoding both genes and their cognate proteins was significantly reduced (>60%) in experimental compared control green fluorescent protein (GFP) siRNA-treated mirids at 48 h post injection. Injury levels of cotton buds were also significantly reduced after injecting saliva isolated from PG3-4 and PG3-5 siRNA-treated A. lucorum. These results demonstrate that these two PG act in A. lucorum elicitation of plant injury. © 2017 Wiley Periodicals, Inc.

A Novel mRNA Level Subtraction Method for Quick Identification of Target-Orientated Uniquely Expressed Genes Between Peanut Immature Pod and Leaf

PubMed Central

2010-01-01

Subtraction technique has been broadly applied for target gene discovery. However, most current protocols apply relative differential subtraction and result in great amount clone mixtures of unique and differentially expressed genes. This makes it more difficult to identify unique or target-orientated expressed genes. In this study, we developed a novel method for subtraction at mRNA level by integrating magnetic particle technology into driver preparation and tester–driver hybridization to facilitate uniquely expressed gene discovery between peanut immature pod and leaf through a single round subtraction. The resulting target clones were further validated through polymerase chain reaction screening using peanut immature pod and leaf cDNA libraries as templates. This study has resulted in identifying several genes expressed uniquely in immature peanut pod. These target genes can be used for future peanut functional genome and genetic engineering research. PMID:21406066

Comparison of TCDD-elicited genome-wide hepatic gene expression in Sprague–Dawley rats and C57BL/6 mice

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

Nault, Rance; Kim, Suntae; Zacharewski, Timothy R., E-mail: tzachare@msu.edu

2013-03-01

Although the structure and function of the AhR are conserved, emerging evidence suggests that downstream effects are species-specific. In this study, rat hepatic gene expression data from the DrugMatrix database (National Toxicology Program) were compared to mouse hepatic whole-genome gene expression data following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For the DrugMatrix study, male Sprague–Dawley rats were gavaged daily with 20 μg/kg TCDD for 1, 3 and 5 days, while female C57BL/6 ovariectomized mice were examined 1, 3 and 7 days after a single oral gavage of 30 μg/kg TCDD. A total of 649 rat and 1386 mouse genes (|fold change| ≥more » 1.5, P1(t) ≥ 0.99) were differentially expressed following treatment. HomoloGene identified 11,708 orthologs represented across the rat Affymetrix 230 2.0 GeneChip (12,310 total orthologs), and the mouse 4 × 44K v.1 Agilent oligonucleotide array (17,578 total orthologs). Comparative analysis found 563 and 922 orthologs differentially expressed in response to TCDD in the rat and mouse, respectively, with 70 responses associated with immune function and lipid metabolism in common to both. Moreover, QRTPCR analysis of Ceacam1, showed divergent expression (induced in rat; repressed in mouse) functionally consistent with TCDD-elicited hepatic steatosis in the mouse but not the rat. Functional analysis identified orthologs involved in nucleotide binding and acetyltransferase activity in rat, while mouse-specific responses were associated with steroid, phospholipid, fatty acid, and carbohydrate metabolism. These results provide further evidence that TCDD elicits species-specific regulation of distinct gene networks, and outlines considerations for future comparisons of publicly available microarray datasets. - Highlights: ► We performed a whole-genome comparison of TCDD-regulated genes in mice and rats. ► Previous species comparisons were extended using data from the DrugMatrix database. ► Less than 15

Genes uniquely expressed in human growth plate chondrocytes uncover a distinct regulatory network.

PubMed

Li, Bing; Balasubramanian, Karthika; Krakow, Deborah; Cohn, Daniel H

2017-12-20

Chondrogenesis is the earliest stage of skeletal development and is a highly dynamic process, integrating the activities and functions of transcription factors, cell signaling molecules and extracellular matrix proteins. The molecular mechanisms underlying chondrogenesis have been extensively studied and multiple key regulators of this process have been identified. However, a genome-wide overview of the gene regulatory network in chondrogenesis has not been achieved. In this study, employing RNA sequencing, we identified 332 protein coding genes and 34 long non-coding RNA (lncRNA) genes that are highly selectively expressed in human fetal growth plate chondrocytes. Among the protein coding genes, 32 genes were associated with 62 distinct human skeletal disorders and 153 genes were associated with skeletal defects in knockout mice, confirming their essential roles in skeletal formation. These gene products formed a comprehensive physical interaction network and participated in multiple cellular processes regulating skeletal development. The data also revealed 34 transcription factors and 11,334 distal enhancers that were uniquely active in chondrocytes, functioning as transcriptional regulators for the cartilage-selective genes. Our findings revealed a complex gene regulatory network controlling skeletal development whereby transcription factors, enhancers and lncRNAs participate in chondrogenesis by transcriptional regulation of key genes. Additionally, the cartilage-selective genes represent candidate genes for unsolved human skeletal disorders.

Reflecting on the use of photo elicitation with children.

PubMed

Whiting, Lisa S

2015-01-01

To reflect on the use of photo elicitation as a data collection method when conducting research with primary school age children (nine to 11 years). There is recognition that children feel an affinity with the visual medium; as a result, visual methods can be useful when conducting research with children. Photo elicitation is one such method, but there has been little discussion of its use with primary school children within a health context. This paper considers the main issues that researchers should consider. This paper draws on a research study conducted by the author that used an ethnographic approach and photo elicitation to identify the assets underpinning children's wellbeing. A reflective discussion is used to highlight issues relating to the use of photo elicitation to collect data from primary school children. Photo elicitation is not without its challenges: it creates additional ethical considerations, and can be more time-consuming and expensive. However, children value the opportunity to be involved in research and have their opinions sought, and photo elicitation provides a method of collecting data that is appropriate for children's developmental and cognitive maturational stages. Photo elicitation can be a positive experience for children, and one that is not only fun and engaging, but that is also empowering and valuing of their contributions. Research that uses photo elicitation needs to be carefully planned to ensure that the study is supported appropriately. The visual process can offer a unique insight into children's lives that allows health professionals to deepen their understanding of children's experiences.

Complete genome sequence of Brachyspira intermedia reveals unique genomic features in Brachyspira species and phage-mediated horizontal gene transfer

PubMed Central

2011-01-01

Background Brachyspira spp. colonize the intestines of some mammalian and avian species and show different degrees of enteropathogenicity. Brachyspira intermedia can cause production losses in chickens and strain PWS/AT now becomes the fourth genome to be completed in the genus Brachyspira. Results 15 classes of unique and shared genes were analyzed in B. intermedia, B. murdochii, B. hyodysenteriae and B. pilosicoli. The largest number of unique genes was found in B. intermedia and B. murdochii. This indicates the presence of larger pan-genomes. In general, hypothetical protein annotations are overrepresented among the unique genes. A 3.2 kb plasmid was found in B. intermedia strain PWS/AT. The plasmid was also present in the B. murdochii strain but not in nine other Brachyspira isolates. Within the Brachyspira genomes, genes had been translocated and also frequently switched between leading and lagging strands, a process that can be followed by different AT-skews in the third positions of synonymous codons. We also found evidence that bacteriophages were being remodeled and genes incorporated into them. Conclusions The accessory gene pool shapes species-specific traits. It is also influenced by reductive genome evolution and horizontal gene transfer. Gene-transfer events can cross both species and genus boundaries and bacteriophages appear to play an important role in this process. A mechanism for horizontal gene transfer appears to be gene translocations leading to remodeling of bacteriophages in combination with broad tropism. PMID:21816042

Transcriptomic sequencing reveals a set of unique genes activated by butyrate-induced histone modification

USDA-ARS?s Scientific Manuscript database

Butyrate is a nutritional element with strong epigenetic regulatory activity as an inhibitor of histone deacetylases (HDACs). Based on the analysis of differentially expressed genes induced by butyrate in the bovine epithelial cell using deep RNA-sequencing technology (RNA-seq), a set of unique gen...

Using process elicitation and validation to understand and improve chemotherapy ordering and delivery.

PubMed

Mertens, Wilson C; Christov, Stefan C; Avrunin, George S; Clarke, Lori A; Osterweil, Leon J; Cassells, Lucinda J; Marquard, Jenna L

2012-11-01

Chemotherapy ordering and administration, in which errors have potentially severe consequences, was quantitatively and qualitatively evaluated by employing process formalism (or formal process definition), a technique derived from software engineering, to elicit and rigorously describe the process, after which validation techniques were applied to confirm the accuracy of the described process. The chemotherapy ordering and administration process, including exceptional situations and individuals' recognition of and responses to those situations, was elicited through informal, unstructured interviews with members of an interdisciplinary team. The process description (or process definition), written in a notation developed for software quality assessment purposes, guided process validation (which consisted of direct observations and semistructured interviews to confirm the elicited details for the treatment plan portion of the process). The overall process definition yielded 467 steps; 207 steps (44%) were dedicated to handling 59 exceptional situations. Validation yielded 82 unique process events (35 new expected but not yet described steps, 16 new exceptional situations, and 31 new steps in response to exceptional situations). Process participants actively altered the process as ambiguities and conflicts were discovered by the elicitation and validation components of the study. Chemotherapy error rates declined significantly during and after the project, which was conducted from October 2007 through August 2008. Each elicitation method and the subsequent validation discussions contributed uniquely to understanding the chemotherapy treatment plan review process, supporting rapid adoption of changes, improved communication regarding the process, and ensuing error reduction.

Identification of unique cis-element pattern on simulated microgravity treated Arabidopsis by in silico and gene expression

NASA Astrophysics Data System (ADS)

Soh, Hyuncheol; Choi, Yongsang; Lee, Taek-Kyun; Yeo, Up-Dong; Han, Kyeongsik; Auh, Chungkyun; Lee, Sukchan

2012-08-01

Arabidopsis gene expression microarray (44 K) was used to detect genes highly induced under simulated microgravity stress (SMS). Ten SMS-inducible genes were selected from the microarray data and these 10 genes were found to be abundantly expressed in 3-week-old plants. Nine out of the 10 SMS-inducible genes were also expressed in response to the three abiotic stresses of drought, touch, and wounding in 3-week-old Arabidopsis plants respectively. However, WRKY46 was elevated only in response to SMS. Six other WRKY genes did not respond to SMS. To clarify the characteristics of the genes expressed at high levels in response to SMS, 20 cis-elements in the promoters of the 40 selected genes including the 10 SMS-inducible genes, the 6 WRKY genes, and abiotic stress-inducible genes were analyzed and their spatial positions on each promoter were determined. Four cis-elements (M/T-G-T-P from MYB1AT or TATABOX5, GT1CONSENSUS, TATABOX5, and POLASIG1) showed a unique spatial arrangement in most SMS-inducible genes including WRKY46. Therefore the M/T-G-T-P cis-element patterns identified in the promoter of WRKY46 may play important roles in regulating gene expression in response to SMS. The presences of the cis-element patterns suggest that the order or spatial positioning of certain groups of cis-elements is more important than the existence or numbers of specific cis-elements. Taken together, our data indicate that WRKY46 is a novel SMS inducible transcription factor and the unique spatial arrangement of cis-elements shown in WRKY46 promoter may play an important role for its response to SMS.

A neural signature of the unique hues

PubMed Central

Forder, Lewis; Bosten, Jenny; He, Xun; Franklin, Anna

2017-01-01

Since at least the 17th century there has been the idea that there are four simple and perceptually pure “unique” hues: red, yellow, green, and blue, and that all other hues are perceived as mixtures of these four hues. However, sustained scientific investigation has not yet provided solid evidence for a neural representation that separates the unique hues from other colors. We measured event-related potentials elicited from unique hues and the ‘intermediate’ hues in between them. We find a neural signature of the unique hues 230 ms after stimulus onset at a post-perceptual stage of visual processing. Specifically, the posterior P2 component over the parieto-occipital lobe peaked significantly earlier for the unique than for the intermediate hues (Z = −2.9, p = 0.004). Having identified a neural marker for unique hues, fundamental questions about the contribution of neural hardwiring, language and environment to the unique hues can now be addressed. PMID:28186142

MiR-204 down-regulation elicited perturbation of a gene target signature common to human cholangiocarcinoma and gastric cancer.

PubMed

Canu, Valeria; Sacconi, Andrea; Lorenzon, Laura; Biagioni, Francesca; Lo Sardo, Federica; Diodoro, Maria Grazia; Muti, Paola; Garofalo, Alfredo; Strano, Sabrina; D'Errico, Antonietta; Grazi, Gian Luca; Cioce, Mario; Blandino, Giovanni

2017-05-02

There is high need of novel diagnostic and prognostic tools for tumors of the digestive system, such as gastric cancer and cholangiocarcinoma. We recently found that miR-204 was deeply downregulated in gastric cancer tissues. Here we investigated whether this was common to other tumors of the digestive system and whether this elicited a miR-204-dependent gene target signature, diagnostically and therapeutically relevant. Finally, we assessed the contribution of the identified target genes to the cell cycle progression and clonogenicity of gastric cancer and cholangiocarcinoma cell lines. We employed quantitative PCR and Affymetrix profiling for gene expression studies. In silico analysis aided us to identifying a miR-204 target signature in publicly available databases (TGCA). We employed transient transfection experiments, clonogenic assays and cell cycle profiling to evaluate the biological consequences of miR-204 perturbation. We identified a novel miR-204 gene target signature perturbed in gastric cancer and in cholangiocarcinoma specimens. We validated its prognostic relevance and mechanistically addressed its biological relevance in GC and CC cell lines. We suggest that restoring the physiological levels of miR-204 in some gastrointestinal cancers might be exploited therapeutically.

A Benzothiadiazole Primes Parsley Cells for Augmented Elicitation of Defense Responses

PubMed Central

Katz, Vera A.; Thulke, Oliver U.; Conrath, Uwe

1998-01-01

Systemic acquired resistance is an important component of the disease-resistance arsenal of plants, and is associated with an enhanced potency for activating local defense responses upon pathogen attack. Here we demonstrate that pretreatment with benzothiadiazole (BTH), a synthetic activator of acquired resistance in plants, augmented the sensitivity for low-dose elicitation of coumarin phytoalexin secretion by cultured parsley (Petroselinum crispum L.) cells. Enhanced coumarin secretion was associated with potentiated activation of genes encoding Phe ammonia-lyase (PAL). The augmentation of PAL gene induction was proportional to the length of pretreatment with BTH, indicating time-dependent priming of the cells. In contrast to the PAL genes, those for anionic peroxidase were directly induced by BTH in the absence of elicitor, thus confirming a dual role for BTH in the activation of plant defenses. Strikingly, the ability of various chemicals to enhance plant disease resistance correlated with their capability to potentiate parsley PAL gene elicitation, emphasizing an important role for defense response potentiation in acquired plant disease resistance. PMID:9701589

Basic Mechanics of DNA Methylation and the Unique Landscape of the DNA Methylome in Metal-Induced Carcinogenesis

PubMed Central

Brocato, Jason; Costa, Max

2013-01-01

DNA methylation plays an intricate role in the regulation of gene expression and events that compromise the integrity of the methylome may potentially contribute to disease development. DNA methylation is a reversible and regulatory modification that elicits a cascade of events leading to chromatin condensation and gene silencing. In general, normal cells are characterized by gene-specific hypomethylation and global hypermethylation, while cancer cells portray a reverse profile to this norm. The unique methylome displayed in cancer cells is induced after exposure to carcinogenic metals such as nickel, arsenic, cadmium, and chromium (VI). These metals alter the DNA methylation profile by provoking both hyper- and hypomethylation events. The metal-stimulated deviations to the methylome are possible mechanisms for metal-induced carcinogenesis and may provide potential biomarkers for cancer detection. Development of therapies based on the cancer methylome requires further research including human studies that supply results with larger impact and higher human relevance. PMID:23844698

Basic mechanics of DNA methylation and the unique landscape of the DNA methylome in metal-induced carcinogenesis.

PubMed

Brocato, Jason; Costa, Max

2013-07-01

DNA methylation plays an intricate role in the regulation of gene expression and events that compromise the integrity of the methylome may potentially contribute to disease development. DNA methylation is a reversible and regulatory modification that elicits a cascade of events leading to chromatin condensation and gene silencing. In general, normal cells are characterized by gene-specific hypomethylation and global hypermethylation, while cancer cells portray a reverse profile to this norm. The unique methylome displayed in cancer cells is induced after exposure to carcinogenic metals such as nickel, arsenic, cadmium, and chromium (VI). These metals alter the DNA methylation profile by provoking both hyper- and hypo-methylation events. The metal-stimulated deviations to the methylome are possible mechanisms for metal-induced carcinogenesis and may provide potential biomarkers for cancer detection. Development of therapies based on the cancer methylome requires further research including human studies that supply results with larger impact and higher human relevance.

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...

LinkIT: a ludic elicitation game for eliciting risk perceptions.

PubMed

Cao, Yan; McGill, William L

2013-06-01

The mental models approach, a leading strategy to develop risk communications, involves a time- and labor-intensive interview process and a lengthy questionnaire to elicit group-level risk perceptions. We propose that a similarity ratings approach for structural knowledge elicitation can be adopted to assist the risk mental models approach. The LinkIT game, inspired by games with a purpose (GWAP) technology, is a ludic elicitation tool designed to elicit group understanding of the relations between risk factors in a more enjoyable and productive manner when compared to traditional approaches. That is, consistent with the idea of ludic elicitation, LinkIT was designed to make the elicitation process fun and enjoyable in the hopes of increasing participation and data quality in risk studies. Like the mental models approach, the group mental model obtained via the LinkIT game can hence be generated and represented in a form of influence diagrams. In order to examine the external validity of LinkIT, we conducted a study to compare its performance with respect to a more conventional questionnaire-driven approach. Data analysis results conclude that the two group mental models elicited from the two approaches are similar to an extent. Yet, LinkIT was more productive and enjoyable than the questionnaire. However, participants commented that the current game has some usability concerns. This presentation summarizes the design and evaluation of the LinkIT game and suggests areas for future work. © 2012 Society for Risk Analysis.

Hydroxymethylation is uniquely distributed within term placenta, and is associated with gene expression.

PubMed

Green, Benjamin B; Houseman, E Andres; Johnson, Kevin C; Guerin, Dylan J; Armstrong, David A; Christensen, Brock C; Marsit, Carmen J

2016-08-01

The conversion of cytosine to 5-methylcystosine (5mC) is an important regulator of gene expression. 5mC may be enzymatically converted to 5-hydroxymethylcytosine (5hmC), with a potentially distinct regulatory function. We sought to investigate these cytosine modifications and their effect on gene expression by parallel processing of genomic DNA using bisulfite and oxidative bisulfite conversion in conjunction with RNA sequencing. Although values of 5hmC across the placental genome were generally low, we identified ∼21,000 loci with consistently elevated levels of 5-hydroxymethycytosine. Absence of 5hmC was observed in CpG islands and, to a greater extent, in non-CpG island-associated regions. 5hmC was enriched within poised enhancers, and depleted within active enhancers, as defined by H3K27ac and H3K4me1 measurements. 5hmC and 5mC were significantly elevated in transcriptionally silent genes when compared with actively transcribed genes. 5hmC was positively associated with transcription in actively transcribed genes only. Our data suggest that dynamic cytosine regulation, associated with transcription, provides the most complete epigenomic landscape of the human placenta, and will be useful for future studies of the placental epigenome.-Green, B. B., Houseman, E. A., Johnson, K. C., Guerin, D. J., Armstrong, D. A., Christensen, B. C., Marsit, C. J. Hydroxymethylation is uniquely distributed within term placenta, and is associated with gene expression. © FASEB.

Hydroxymethylation is uniquely distributed within term placenta, and is associated with gene expression

PubMed Central

Green, Benjamin B.; Houseman, E. Andres; Johnson, Kevin C.; Guerin, Dylan J.; Armstrong, David A.; Christensen, Brock C.; Marsit, Carmen J.

2016-01-01

The conversion of cytosine to 5-methylcystosine (5mC) is an important regulator of gene expression. 5mC may be enzymatically converted to 5-hydroxymethylcytosine (5hmC), with a potentially distinct regulatory function. We sought to investigate these cytosine modifications and their effect on gene expression by parallel processing of genomic DNA using bisulfite and oxidative bisulfite conversion in conjunction with RNA sequencing. Although values of 5hmC across the placental genome were generally low, we identified ∼21,000 loci with consistently elevated levels of 5-hydroxymethycytosine. Absence of 5hmC was observed in CpG islands and, to a greater extent, in non-CpG island–associated regions. 5hmC was enriched within poised enhancers, and depleted within active enhancers, as defined by H3K27ac and H3K4me1 measurements. 5hmC and 5mC were significantly elevated in transcriptionally silent genes when compared with actively transcribed genes. 5hmC was positively associated with transcription in actively transcribed genes only. Our data suggest that dynamic cytosine regulation, associated with transcription, provides the most complete epigenomic landscape of the human placenta, and will be useful for future studies of the placental epigenome.—Green, B. B., Houseman, E. A., Johnson, K. C., Guerin, D. J., Armstrong, D. A., Christensen, B. C., Marsit, C. J. Hydroxymethylation is uniquely distributed within term placenta, and is associated with gene expression. PMID:27118675

Patterns on serpentine shapes elicit visual attention in marmosets (Callithrix jacchus).

PubMed

Wombolt, Jessica R; Caine, Nancy G

2016-09-01

Given the prevalence of threatening snakes in the evolutionary history, and modern-day environments of human and nonhuman primates, sensory, and perceptual abilities that allow for quick detection of, and appropriate response to snakes are likely to have evolved. Many studies have demonstrated that primates recognize snakes faster than other stimuli, and it is suggested that the unique serpentine shape is responsible for its quick detection. However, there are many nonthreatening serpentine shapes in the environment (e.g., vines) that are not threatening; therefore, other cues must be used to distinguish threatening from benign serpentine objects. In two experiments, we systematically evaluated how common marmosets (Callithrix jacchus) visually attend to specific snake-like features. In the first experiment, we examined if skin pattern is a cue that elicits increased visual inspection of serpentine shapes by measuring the amount of time the marmosets looked into a blind before, during, and after presentation of clay models with and without patterns. The marmosets spent the most time looking at the objects, both serpentine and triangle, that were etched with scales, suggesting that something may be uniquely salient about scales in evoking attention. In contrast, they showed relatively little interest in the unpatterned serpentine and control (a triangle) stimuli. In experiment 2, we replicated and extended the results of experiment 1 by adding additional stimulus conditions. We found that patterns on a serpentine shape generated more inspection than those same patterns on a triangle shape. We were unable to confirm that a scaled pattern is unique in its ability to elicit visual interest; the scaled models elicited similar looking times as line and star patterns. Our data provide a foundation for future research to examine how snakes are detected and identified by primates. Am. J. Primatol. 78:928-936, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals

Targeting of Repeated Sequences Unique to a Gene Results in Significant Increases in Antisense Oligonucleotide Potency

PubMed Central

Vickers, Timothy A.; Freier, Susan M.; Bui, Huynh-Hoa; Watt, Andrew; Crooke, Stanley T.

2014-01-01

A new strategy for identifying potent RNase H-dependent antisense oligonucleotides (ASOs) is presented. Our analysis of the human transcriptome revealed that a significant proportion of genes contain unique repeated sequences of 16 or more nucleotides in length. Activities of ASOs targeting these repeated sites in several representative genes were compared to those of ASOs targeting unique single sites in the same transcript. Antisense activity at repeated sites was also evaluated in a highly controlled minigene system. Targeting both native and minigene repeat sites resulted in significant increases in potency as compared to targeting of non-repeated sites. The increased potency at these sites is a result of increased frequency of ASO/RNA interactions which, in turn, increases the probability of a productive interaction between the ASO/RNA heteroduplex and human RNase H1 in the cell. These results suggest a new, highly efficient strategy for rapid identification of highly potent ASOs. PMID:25334092

Cocoa butter and safflower oil elicit different effects on hepatic gene expression and lipid metabolism in rats.

PubMed

Gustavsson, Carolina; Parini, Paolo; Ostojic, Jovanca; Cheung, Louisa; Hu, Jin; Zadjali, Fahad; Tahir, Faheem; Brismar, Kerstin; Norstedt, Gunnar; Tollet-Egnell, Petra

2009-11-01

The aim of this study was to compare the effects of cocoa butter and safflower oil on hepatic transcript profiles, lipid metabolism and insulin sensitivity in healthy rats. Cocoa butter-based high-fat feeding for 3 days did not affect plasma total triglyceride (TG) levels or TG-rich VLDL particles or hepatic insulin sensitivity, but changes in hepatic gene expression were induced that might lead to increased lipid synthesis, lipotoxicity, inflammation and insulin resistance if maintained. Safflower oil increased hepatic beta-oxidation, was beneficial in terms of circulating TG-rich VLDL particles, but led to reduced hepatic insulin sensitivity. The effects of safflower oil on hepatic gene expression were partly overlapping with those exerted by cocoa butter, but fewer transcripts from anabolic pathways were altered. Increased hepatic cholesterol levels and increased expression of hepatic CYP7A1 and ABCG5 mRNA, important gene products in bile acid production and cholesterol excretion, were specific effects elicited by safflower oil only. Common effects on gene expression included increased levels of p8, DIG-1 IGFBP-1 and FGF21, and reduced levels of SCD-1 and SCD-2. This indicates that a lipid-induced program for hepatic lipid disposal and cell survival was induced by 3 days of high-fat feeding, independent on the lipid source. Based on the results, we speculate that hepatic TG infiltration leads to reduced expression of SCD-1, which might mediate either neutral, beneficial or unfavorable effects on hepatic metabolism upon high-fat feeding, depending on which fatty acids were provided by the diet.

Different Vaccine Vectors Delivering the Same Antigen Elicit CD8+ T Cell Responses with Distinct Clonotype and Epitope Specificity

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

Honda, M.; Robinson, H.; Wang, R.

Prime-boost immunization with gene-based vectors has been developed to generate more effective vaccines for AIDS, malaria, and tuberculosis. Although these vectors elicit potent T cell responses, the mechanisms by which they stimulate immunity are not well understood. In this study, we show that immunization by a single gene product, HIV-1 envelope, with alternative vector combinations elicits CD8{sup +} cells with different fine specificities and kinetics of mobilization. Vaccine-induced CD8{sup +} T cells recognized overlapping third V region loop peptides. Unexpectedly, two anchor variants bound H-2D{sup d} better than the native sequences, and clones with distinct specificities were elicited by alternativemore » vectors. X-ray crystallography revealed major differences in solvent exposure of MHC-bound peptide epitopes, suggesting that processed HIV-1 envelope gave rise to MHC-I/peptide conformations recognized by distinct CD8{sup +} T cell populations. These findings suggest that different gene-based vectors generate peptides with alternative conformations within MHC-I that elicit distinct T cell responses after vaccination.« less

The Unique hmuY Gene Sequence as a Specific Marker of Porphyromonas gingivalis

PubMed Central

Mackiewicz, Paweł; Radwan-Oczko, Małgorzata; Kantorowicz, Małgorzata; Chomyszyn-Gajewska, Maria; Frąszczak, Magdalena; Bielecki, Marcin; Olczak, Mariusz; Olczak, Teresa

2013-01-01

Porphyromonas gingivalis, a major etiological agent of chronic periodontitis, acquires heme from host hemoproteins using the HmuY hemophore. The aim of this study was to develop a specific P. gingivalis marker based on a hmuY gene sequence. Subgingival samples were collected from 66 patients with chronic periodontitis and 40 healthy subjects and the entire hmuY gene was analyzed in positive samples. Phylogenetic analyses demonstrated that both the amino acid sequence of the HmuY protein and the nucleotide sequence of the hmuY gene are unique among P. gingivalis strains/isolates and show low identity to sequences found in other species (below 50 and 56%, respectively). In agreement with these findings, a set of hmuY gene-based primers and standard/real-time PCR with SYBR Green chemistry allowed us to specifically detect P. gingivalis in patients with chronic periodontitis (77.3%) and healthy subjects (20%), the latter possessing lower number of P. gingivalis cells and total bacterial cells. Isolates from healthy subjects possess the hmuY gene-based nucleotide sequence pattern occurring in W83/W50/A7436 (n = 4), 381/ATCC 33277 (n = 3) or TDC60 (n = 1) strains, whereas those from patients typically have TDC60 (n = 21), W83/W50/A7436 (n = 17) and 381/ATCC 33277 (n = 13) strains. We observed a significant correlation between periodontal index of risk of infectiousness (PIRI) and the presence/absence of P. gingivalis (regardless of the hmuY gene-based sequence pattern of the isolate identified [r = 0.43; P = 0.0002] and considering particular isolate pattern [r = 0.38; P = 0.0012]). In conclusion, we demonstrated that the hmuY gene sequence or its fragments may be used as one of the molecular markers of P. gingivalis. PMID:23844074

Toxic genes present a unique phylogenetic signature.

PubMed

Avni, Eliran; Snir, Sagi

2017-11-01

Horizontal gene transfer (HGT) is a major part of the evolution of Archaea and Bacteria, to the extent that the validity of the Tree of Life concept for prokaryotes has been seriously questioned. The patterns and routes of HGT remain a subject of intense study and debate. It was discovered that while several genes exhibit rampant HGT across the whole prokaryotic tree of life, others are lethal to certain organisms and therefore cannot be successfully transferred to them. We distinguish between these two classes of genes and show analytically that genes found to be toxic to a specific species (E. coli) also resist HGT in general. Several tools we employ show evidence to support that claim. One of those tools is the quartet plurality distribution (QPD), a mathematical tool that measures tendency to HGT over a large set of genes and species. When aggregated over a collection of genes, it can reveal important properties of this collection. We conclude that evidence of toxicity of certain genes to a wide variety of prokaryotes are revealed using the new tool of quartet plurality distribution. Copyright © 2017 Elsevier Inc. All rights reserved.

Different Vaccine Vectors Delivering the Same Antigen Elicit CD8plus T Cell Responses with Distinct Clonotype and Epitope Specificity

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

M Honda; R Wang; W Kong

Prime-boost immunization with gene-based vectors has been developed to generate more effective vaccines for AIDS, malaria, and tuberculosis. Although these vectors elicit potent T cell responses, the mechanisms by which they stimulate immunity are not well understood. In this study, we show that immunization by a single gene product, HIV-1 envelope, with alternative vector combinations elicits CD8{sup +} cells with different fine specificities and kinetics of mobilization. Vaccine-induced CD8{sup +} T cells recognized overlapping third V region loop peptides. Unexpectedly, two anchor variants bound H-2D{sup d} better than the native sequences, and clones with distinct specificities were elicited by alternativemore » vectors. X-ray crystallography revealed major differences in solvent exposure of MHC-bound peptide epitopes, suggesting that processed HIV-1 envelope gave rise to MHC-I/peptide conformations recognized by distinct CD8{sup +} T cell populations. These findings suggest that different gene-based vectors generate peptides with alternative conformations within MHC-I that elicit distinct T cell responses after vaccination.« less

Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures

PubMed Central

Park, Paul J.; Fuchs, Robert; Wei, Lai; Jorgensen, Brian G.; Redelman, Doug; Ward, Sean M.; Sanders, Kenton M.

2017-01-01

Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC), which serve as slow-wave electrical pacemakers for gastrointestinal (GI) smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes. In analyzing the transcriptome, we identified a unique set of ICC-restricted markers including transcription factors, epigenetic enzymes/regulators, growth factors, receptors, protein kinases/phosphatases, and ion channels/transporters. This analysis provides new and unique insights into the cellular and biological functions of ICC in GI physiology. Additionally, we constructed an interactive ICC genome browser (http://med.unr.edu/physio/transcriptome) based on the UCSC genome database. To our knowledge, this is the first online resource that provides a comprehensive library of all known genetic transcripts expressed in primary ICC. Our genome browser offers a new perspective into the alternative expression of genes in ICC and provides a valuable reference for future functional studies. PMID:28426719

The MB2 gene family of Plasmodium species has a unique combination of S1 and GTP-binding domains

PubMed Central

Romero, Lisa C; Nguyen, Thanh V; Deville, Benoit; Ogunjumo, Oluwasanmi; James, Anthony A

2004-01-01

Background Identification and characterization of novel Plasmodium gene families is necessary for developing new anti-malarial therapeutics. The products of the Plasmodium falciparum gene, MB2, were shown previously to have a stage-specific pattern of subcellular localization and proteolytic processing. Results Genes homologous to MB2 were identified in five additional parasite species, P. knowlesi, P. gallinaceum, P. berghei, P. yoelii, and P. chabaudi. Sequence comparisons among the MB2 gene products reveal amino acid conservation of structural features, including putative S1 and GTP-binding domains, and putative signal peptides and nuclear localization signals. Conclusions The combination of domains is unique to this gene family and indicates that MB2 genes comprise a novel family and therefore may be a good target for drug development. PMID:15222903

Unique gene expression profiles of donor-matched human retinal and choroidal vascular endothelial cells.

PubMed

Smith, Justine R; Choi, Dongseok; Chipps, Timothy J; Pan, Yuzhen; Zamora, David O; Davies, Michael H; Babra, Bobby; Powers, Michael R; Planck, Stephen R; Rosenbaum, James T

2007-06-01

Consistent with clinical observations that posterior uveitis frequently involves the retinal vasculature and recent recognition of vascular heterogeneity, the hypothesis for this study was that retinal vascular endothelium was a cell population of unique molecular phenotype. Donor-matched cultures of primary retinal and choroidal endothelial cells from six human cadavers were incubated with either Toxoplasma gondii tachyzoites (10:1, parasites per cell) or Escherichia coli lipopolysaccharide (100 ng/mL); control cultures were simultaneously incubated with medium. Gene expression profiling of endothelial cells was performed using oligonucleotide arrays containing probes designed to detect 8746 human transcripts. After normalization, differential gene expression was assessed by the significance analysis of microarrays, with the false-discovery rate set at 5%. For selected genes, differences in the level of expression between retinal and choroidal cells were evaluated by real-time RT-PCR. Graphic descriptive analysis demonstrated a strong correlation between gene expression of unstimulated retinal and choroidal endothelial cells, but also highlighted distinctly different patterns of expression that were greater than differences noted between donors or between unstimulated and stimulated cells. Overall, 779 (8.9%) of 8746 transcripts were differentially represented. Of note, the 330 transcripts that were present at higher levels in retinal cells included a larger percentage of transcripts encoding molecules involved in the immune response. Differential gene expression was confirmed for 12 transcripts by RT-PCR. Retinal and choroidal vascular endothelial cells display distinctive gene expression profiles. The findings suggest the possibility of treating posterior uveitis by targeting specific interactions between the retinal endothelial cell and an infiltrating leukocyte.

Overlap Chronic Placental Inflammation Is Associated with a Unique Gene Expression Pattern.

PubMed

Raman, Kripa; Wang, Huaqing; Troncone, Michael J; Khan, Waliul I; Pare, Guillaume; Terry, Jefferson

2015-01-01

Breakdown of the balance between maternal pro- and anti-inflammatory pathways is thought to allow an anti-fetal maternal immune response that underlies development of chronic placental inflammation. Chronic placental inflammation is manifested by the influx of maternal inflammatory cells, including lymphocytes, histiocytes, and plasma cells, into the placental membranes, villi, and decidua. These infiltrates are recognized pathologically as chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. Each of these histological entities is associated with adverse fetal outcomes including intrauterine growth restriction and preterm birth. Studying the gene expression patterns in chronically inflamed placenta, particularly when overlapping histologies are present, may lead to a better understanding of the underlying mechanism(s). Therefore, this study compared tissue with and without chronic placental inflammation, manifested as overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. RNA expression profiling was conducted on formalin fixed, paraffin embedded placental tissue using Illumina microarrays. IGJ was the most significant differentially expressed gene identified and had increased expression in the inflamed tissue. In addition, IGLL1, CXCL13, CD27, CXCL9, ICOS, and KLRC1 had increased expression in the inflamed placental samples. These differentially expressed genes are associated with T follicular helper cells, natural killer cells, and B cells. Furthermore, these genes differ from those typically associated with the individual components of chronic placental inflammation, such as chronic villitis, suggesting that the inflammatory infiltrate associated with overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis differs is unique. To further explore and validate gene expression findings, we conducted immunohistochemical assessment of protein level

Genetic homogeneity of Clostridium botulinum type A1 strains with unique toxin gene clusters.

PubMed

Raphael, Brian H; Luquez, Carolina; McCroskey, Loretta M; Joseph, Lavin A; Jacobson, Mark J; Johnson, Eric A; Maslanka, Susan E; Andreadis, Joanne D

2008-07-01

A group of five clonally related Clostridium botulinum type A strains isolated from different sources over a period of nearly 40 years harbored several conserved genetic properties. These strains contained a variant bont/A1 with five nucleotide polymorphisms compared to the gene in C. botulinum strain ATCC 3502. The strains also had a common toxin gene cluster composition (ha-/orfX+) similar to that associated with bont/A in type A strains containing an unexpressed bont/B [termed A(B) strains]. However, bont/B was not identified in the strains examined. Comparative genomic hybridization demonstrated identical genomic content among the strains relative to C. botulinum strain ATCC 3502. In addition, microarray data demonstrated the absence of several genes flanking the toxin gene cluster among the ha-/orfX+ A1 strains, suggesting the presence of genomic rearrangements with respect to this region compared to the C. botulinum ATCC 3502 strain. All five strains were shown to have identical flaA variable region nucleotide sequences. The pulsed-field gel electrophoresis patterns of the strains were indistinguishable when digested with SmaI, and a shift in the size of at least one band was observed in a single strain when digested with XhoI. These results demonstrate surprising genomic homogeneity among a cluster of unique C. botulinum type A strains of diverse origin.

Vibrio elicits targeted transcriptional responses from copepod hosts.

PubMed

Almada, Amalia A; Tarrant, Ann M

2016-06-01

Copepods are abundant crustaceans that harbor diverse bacterial communities, yet the nature of their interactions with microbiota are poorly understood. Here, we report that Vibrio elicits targeted transcriptional responses in the estuarine copepod Eurytemora affinis We pre-treated E. affinis with an antibiotic cocktail and exposed them to either a zooplankton specialist (Vibrio sp. F10 9ZB36) or a free-living species (Vibrio ordalii 12B09) for 24 h. We then identified via RNA-Seq a total of 78 genes that were differentially expressed following Vibrio exposure, including homologs of C-type lectins, chitin-binding proteins and saposins. The response differed between the two Vibrio treatments, with the greatest changes elicited upon inoculation with V. sp. F10 We suggest that these differentially regulated genes play important roles in cuticle integrity, the innate immune response, and general stress response, and that their expression may enable E. affinis to recognize and regulate symbiotic vibrios. We further report that V. sp. F10 culturability is specifically altered upon colonization of E. affinis These findings suggest that rather than acting as passive environmental vectors, copepods discriminately interact with vibrios, which may ultimately impact the abundance and activity of copepod-associated bacteria. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Heterogeneous Stock Rat: A Unique Animal Model for Mapping Genes Influencing Bone Fragility

PubMed Central

Alam, Imranul; Koller, Daniel L.; Sun, Qiwei; Roeder, Ryan K.; Cañete, Toni; Blázquez, Gloria; López-Aumatell, Regina; Martínez-Membrives, Esther; Vicens-Costa, Elia; Mont, Carme; Díaz, Sira; Tobeña, Adolf; Fernández-Teruel, Alberto; Whitley, Adam; Strid, Pernilla; Diez, Margarita; Johannesson, Martina; Flint, Jonathan; Econs, Michael J.; Turner, Charles H.; Foroud, Tatiana

2011-01-01

Previously, we demonstrated that skeletal mass, structure and biomechanical properties vary considerably among 11 different inbred rat strains. Subsequently, we performed quantitative trait loci (QTL) analysis in 4 inbred rat strains (F344, LEW, COP and DA) for different bone phenotypes and identified several candidate genes influencing various bone traits. The standard approach to narrowing QTL intervals down to a few candidate genes typically employs the generation of congenic lines, which is time consuming and often not successful. A potential alternative approach is to use a highly genetically informative animal model resource capable of delivering very high-resolution gene mapping such as Heterogeneous stock (HS) rat. HS rat was derived from eight inbred progenitors: ACI/N, BN/SsN, BUF/N, F344/N, M520/N, MR/N, WKY/N and WN/N. The genetic recombination pattern generated across 50 generations in these rats has been shown to deliver ultra-high even gene-level resolution for complex genetic studies. The purpose of this study is to investigate the usefulness of the HS rat model for fine mapping and identification of genes underlying bone fragility phenotypes. We compared bone geometry, density and strength phenotypes at multiple skeletal sites in HS rats with those obtained from 5 of the 8 progenitor inbred strains. In addition, we estimated the heritability for different bone phenotypes in these rats and employed principal component analysis to explore relationships among bone phenotypes in the HS rats. Our study demonstrates that significant variability exists for different skeletal phenotypes in HS rats compared with their inbred progenitors. In addition, we estimated high heritability for several bone phenotypes and biologically interpretable factors explaining significant overall variability, suggesting that the HS rat model could be a unique genetic resource for rapid and efficient discovery of the genetic determinants of bone fragility. PMID:21334473

Heterogeneous stock rat: a unique animal model for mapping genes influencing bone fragility.

PubMed

Alam, Imranul; Koller, Daniel L; Sun, Qiwei; Roeder, Ryan K; Cañete, Toni; Blázquez, Gloria; López-Aumatell, Regina; Martínez-Membrives, Esther; Vicens-Costa, Elia; Mont, Carme; Díaz, Sira; Tobeña, Adolf; Fernández-Teruel, Alberto; Whitley, Adam; Strid, Pernilla; Diez, Margarita; Johannesson, Martina; Flint, Jonathan; Econs, Michael J; Turner, Charles H; Foroud, Tatiana

2011-05-01

Previously, we demonstrated that skeletal mass, structure and biomechanical properties vary considerably among 11 different inbred rat strains. Subsequently, we performed quantitative trait loci (QTL) analysis in four inbred rat strains (F344, LEW, COP and DA) for different bone phenotypes and identified several candidate genes influencing various bone traits. The standard approach to narrowing QTL intervals down to a few candidate genes typically employs the generation of congenic lines, which is time consuming and often not successful. A potential alternative approach is to use a highly genetically informative animal model resource capable of delivering very high resolution gene mapping such as Heterogeneous stock (HS) rat. HS rat was derived from eight inbred progenitors: ACI/N, BN/SsN, BUF/N, F344/N, M520/N, MR/N, WKY/N and WN/N. The genetic recombination pattern generated across 50 generations in these rats has been shown to deliver ultra-high even gene-level resolution for complex genetic studies. The purpose of this study is to investigate the usefulness of the HS rat model for fine mapping and identification of genes underlying bone fragility phenotypes. We compared bone geometry, density and strength phenotypes at multiple skeletal sites in HS rats with those obtained from five of the eight progenitor inbred strains. In addition, we estimated the heritability for different bone phenotypes in these rats and employed principal component analysis to explore relationships among bone phenotypes in the HS rats. Our study demonstrates that significant variability exists for different skeletal phenotypes in HS rats compared with their inbred progenitors. In addition, we estimated high heritability for several bone phenotypes and biologically interpretable factors explaining significant overall variability, suggesting that the HS rat model could be a unique genetic resource for rapid and efficient discovery of the genetic determinants of bone fragility. Copyright �

ELICIT: An alternative imprecise weight elicitation technique for use in multi-criteria decision analysis for healthcare.

PubMed

Diaby, Vakaramoko; Sanogo, Vassiki; Moussa, Kouame Richard

2016-01-01

In this paper, the readers are introduced to ELICIT, an imprecise weight elicitation technique for multicriteria decision analysis for healthcare. The application of ELICIT consists of two steps: the rank ordering of evaluation criteria based on decision-makers' (DMs) preferences using the principal component analysis; and the estimation of criteria weights and their descriptive statistics using the variable interdependent analysis and the Monte Carlo method. The application of ELICIT is illustrated with a hypothetical case study involving the elicitation of weights for five criteria used to select the best device for eye surgery. The criteria were ranked from 1-5, based on a strict preference relationship established by the DMs. For each criterion, the deterministic weight was estimated as well as the standard deviation and 95% credibility interval. ELICIT is appropriate in situations where only ordinal DMs' preferences are available to elicit decision criteria weights.

An oral Sindbis virus replicon-based DNA vaccine containing VP2 gene of canine parvovirus delivered by Escherichia coli elicits immune responses in dogs.

PubMed

Dahiya, S S; Saini, M; Kumar, P; Gupta, P K

2011-01-01

A Sindbis virus replicon-based DNA vaccine containing VP2 gene of canine parvovirus (CPV) was delivered by Escherichia coli to elicit immune responses. The orally immunized dogs developed CPV-specific serum IgG and virus neutralizing antibody responses. The cellular immune responses analyzed using lymphocyte proliferation test and flow cytometry indicated CPV-specific sensitization of both CD3+CD4+ and CD3+CD8+ lymphocytes. This study demonstrated that the oral CPV DNA vaccine delivered by E. coli can be considered as a promising approach for vaccination of dogs against CPV.

ELICIT: An alternative imprecise weight elicitation technique for use in multi-criteria decision analysis for healthcare

PubMed Central

Diaby, Vakaramoko; Sanogo, Vassiki; Moussa, Kouame Richard

2015-01-01

Objective In this paper, the readers are introduced to ELICIT, an imprecise weight elicitation technique for multicriteria decision analysis for healthcare. Methods The application of ELICIT consists of two steps: the rank ordering of evaluation criteria based on decision-makers’ (DMs) preferences using the principal component analysis; and the estimation of criteria weights and their descriptive statistics using the variable interdependent analysis and the Monte Carlo method. The application of ELICIT is illustrated with a hypothetical case study involving the elicitation of weights for five criteria used to select the best device for eye surgery. Results The criteria were ranked from 1–5, based on a strict preference relationship established by the DMs. For each criterion, the deterministic weight was estimated as well as the standard deviation and 95% credibility interval. Conclusions ELICIT is appropriate in situations where only ordinal DMs’ preferences are available to elicit decision criteria weights. PMID:26361235

Identification of Genes Uniquely Expressed in the Germ-Line Tissues of the Jewel Wasp Nasonia vitripennis

PubMed Central

Ferree, Patrick M.; Fang, Christopher; Mastrodimos, Mariah; Hay, Bruce A.; Amrhein, Henry; Akbari, Omar S.

2015-01-01

The jewel wasp Nasonia vitripennis is a rising model organism for the study of haplo-diploid reproduction characteristic of hymenopteran insects, which include all wasps, bees, and ants. We performed transcriptional profiling of the ovary, the female soma, and the male soma of N. vitripennis to complement a previously existing transcriptome of the wasp testis. These data were deposited into an open-access genome browser for visualization of transcripts relative to their gene models. We used these data to identify the assemblies of genes uniquely expressed in the germ-line tissues. We found that 156 protein-coding genes are expressed exclusively in the wasp testis compared with only 22 in the ovary. Of the testis-specific genes, eight are candidates for male-specific DNA packaging proteins known as protamines. We found very similar expression patterns of centrosome associated genes in the testis and ovary, arguing that de novo centrosome formation, a key process for development of unfertilized eggs into males, likely does not rely on large-scale transcriptional differences between these tissues. In contrast, a number of meiosis-related genes show a bias toward testis-specific expression, despite the lack of true meiosis in N. vitripennis males. These patterns may reflect an unexpected complexity of male gamete production in the haploid males of this organism. Broadly, these data add to the growing number of genomic and genetic tools available in N. vitripennis for addressing important biological questions in this rising insect model organism. PMID:26464360

The unique and cooperative roles of the Grainy head-like transcription factors in epidermal development reflect unexpected target gene specificity.

PubMed

Boglev, Yeliz; Wilanowski, Tomasz; Caddy, Jacinta; Parekh, Vishwas; Auden, Alana; Darido, Charbel; Hislop, Nikki R; Cangkrama, Michael; Ting, Stephen B; Jane, Stephen M

2011-01-15

The Grainy head-like 3 (Grhl3) gene encodes a transcription factor that plays essential roles in epidermal morphogenesis during embryonic development, with deficient mice exhibiting failed skin barrier formation, defective wound repair, and loss of eyelid fusion. Despite sharing significant sequence homology, overlapping expression patterns, and an identical core consensus DNA binding site, the other members of the Grhl family (Grhl1 and -2) fail to compensate for the loss of Grhl3 in these processes. Here, we have employed diverse genetic models, coupled with biochemical studies, to define the inter-relationships of the Grhl factors in epidermal development. We show that Grhl1 and Grhl3 have evolved complete functional independence, as evidenced by a lack of genetic interactions in embryos carrying combinations of targeted alleles of these genes. In contrast, compound heterozygous Grhl2/Grhl3 embryos displayed failed wound repair, and loss of a single Grhl2 allele in Grhl3-null embryos results in fully penetrant eyes open at birth. Expression of Grhl2 from the Grhl3 locus in homozygous knock-in mice corrects the wound repair defect, but these embryos still display a complete failure of skin barrier formation. This functional dissociation is due to unexpected differences in target gene specificity, as both GRHL2 and GRHL3 bind to and regulate expression of the wound repair gene Rho GEF 19, but regulation of the barrier forming gene, Transglutaminase 1 (TGase1), is unique to GRHL3. Our findings define the mechanisms underpinning the unique and cooperative roles of the Grhl genes in epidermal development. Copyright © 2010 Elsevier Inc. All rights reserved.

TCDD and a putative endogenous AhR ligand, ITE, elicit the same immediate changes in gene expression in mouse lung fibroblasts.

PubMed

Henry, Ellen C; Welle, Stephen L; Gasiewicz, Thomas A

2010-03-01

The aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, mediates toxicity of several classes of xenobiotics and also has important physiological roles in differentiation, reproduction, and immunity, although the endogenous ligand(s) mediating these functions is/are as yet unidentified. One candidate endogenous ligand, 2-(1'H-indolo-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), is a potent AhR agonist in vitro, activates the murine AhR in vivo, but does not induce toxicity. We hypothesized that ITE and the toxic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may modify transcription of different sets of genes to account for their different toxicity. To test this hypothesis, primary mouse lung fibroblasts were exposed to 0.5muM ITE, 0.2nM TCDD, or vehicle for 4 h, and total gene expression was evaluated using microarrays. After this short-term and low-dose treatment, several hundred genes were changed significantly, and the response to ITE and TCDD was remarkably similar, both qualitatively and quantitatively. Induced gene sets included the expected battery of AhR-dependent xenobiotic-metabolizing enzymes, as well as several sets that reflect the inflammatory role of lung fibroblasts. Real time quantitative RT-qPCR assay of several selected genes confirmed these microarray data and further suggested that there may be kinetic differences in expression between ligands. These data suggest that ITE and TCDD elicit an analogous change in AhR conformation such that the initial transcription response is the same. Furthermore, if the difference in toxicity between TCDD and ITE is mediated by differences in gene expression, then it is likely that secondary changes enabled by the persistent TCDD, but not by the shorter lived ITE, are responsible.

TCDD and a Putative Endogenous AhR Ligand, ITE, Elicit the Same Immediate Changes in Gene Expression in Mouse Lung Fibroblasts

PubMed Central

Henry, Ellen C.; Welle, Stephen L.; Gasiewicz, Thomas A.

2010-01-01

The aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, mediates toxicity of several classes of xenobiotics and also has important physiological roles in differentiation, reproduction, and immunity, although the endogenous ligand(s) mediating these functions is/are as yet unidentified. One candidate endogenous ligand, 2-(1′H-indolo-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), is a potent AhR agonist in vitro, activates the murine AhR in vivo, but does not induce toxicity. We hypothesized that ITE and the toxic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may modify transcription of different sets of genes to account for their different toxicity. To test this hypothesis, primary mouse lung fibroblasts were exposed to 0.5μM ITE, 0.2nM TCDD, or vehicle for 4 h, and total gene expression was evaluated using microarrays. After this short-term and low-dose treatment, several hundred genes were changed significantly, and the response to ITE and TCDD was remarkably similar, both qualitatively and quantitatively. Induced gene sets included the expected battery of AhR-dependent xenobiotic-metabolizing enzymes, as well as several sets that reflect the inflammatory role of lung fibroblasts. Real time quantitative RT-qPCR assay of several selected genes confirmed these microarray data and further suggested that there may be kinetic differences in expression between ligands. These data suggest that ITE and TCDD elicit an analogous change in AhR conformation such that the initial transcription response is the same. Furthermore, if the difference in toxicity between TCDD and ITE is mediated by differences in gene expression, then it is likely that secondary changes enabled by the persistent TCDD, but not by the shorter lived ITE, are responsible. PMID:19933214

Unique Epstein-Barr virus (EBV) latent gene expression, EBNA promoter usage and EBNA promoter methylation status in chronic active EBV infection.

PubMed

Yoshioka, Mikio; Kikuta, Hideaki; Ishiguro, Nobuhisa; Ma, Xiaoming; Kobayashi, Kunihiko

2003-05-01

Chronic active Epstein-Barr virus infection (CAEBV) has been considered to be a non-neoplastic T-cell lymphoproliferative disease associated with Epstein-Barr virus (EBV) infection. In EBV-associated diseases, the cell phenotype-dependent differences in EBV latent gene expression may reflect the strategy of the virus in relation to latent infection. We previously reported that EBV latent gene expression was restricted; EBV nuclear antigen 1 (EBNA1) transcripts were consistently detected in all spleen samples from five CAEBV patients, but EBNA2 transcripts were detected in only one sample. EBV latent gene expression is controlled by distinct usage of three EBNA promoters (Cp, Wp and Qp). In this study, we examined the EBNA promoter usage by RT-PCR and the methylation status in the Cp and Wp regions using bisulfite PCR analysis in spleen samples from CAEBV patients. EBNA1 transcripts were unexpectedly initiated not from Qp but from Cp in all samples in spite of the restricted form of latency. Furthermore, while Cp was active, Cp was heavily methylated, indicating that CAEBV has unique EBV latent gene expression, EBNA promoter usage and EBNA promoter methylation status, in part due to unique splicing of Cp-initiated transcripts and an activation mechanism in hypermethylated Cp.

Ludic Elicitation: Using Games for Knowledge Elicitation

ERIC Educational Resources Information Center

Cao, Yan

2014-01-01

Knowledge elicitation from human beings is important for many fields, such as decision support systems, risk communication, and customer preference studying. Traditional approaches include observations, questionnaires, structured and semi-structured interviews, and group discussions. Many publications have been studying different techniques for a…

RNA-Seq reveals common and unique PXR- and CAR-target gene signatures in the mouse liver transcriptome.

PubMed

Cui, Julia Yue; Klaassen, Curtis D

2016-09-01

The pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are well-known xenobiotic-sensing nuclear receptors with overlapping functions. However, there lacks a quantitative characterization to distinguish between the PXR and CAR target genes and signaling pathways in the liver. The present study performed a transcriptomic comparison of the PXR- and CAR-targets using RNA-Seq in livers of adult wild-type mice that were treated with the prototypical PXR ligand PCN (200mg/kg, i.p. once daily for 4days in corn oil) or the prototypical CAR ligand TCPOBOP (3mg/kg, i.p., once daily for 4days in corn oil). At the given doses, TCPOBOP differentially regulated many more genes (2125) than PCN (212), and 147 of the same genes were differentially regulated by both chemicals. As expected, the top pathways differentially regulated by both PCN and TCPOBOP were involved in xenobiotic metabolism, and they also up-regulated genes involved in retinoid metabolism, but down-regulated genes involved in inflammation and iron homeostasis. Regarding unique pathways, PXR activation appeared to overlap with the aryl hydrocarbon receptor signaling, whereas CAR activation appeared to overlap with the farnesoid X receptor signaling, acute-phase response, and mitochondrial dysfunction. The mRNAs of differentially regulated drug-processing genes (DPGs) partitioned into three patterns, namely TCPOBOP-induced, PCN-induced, as well as TCPOBOP-suppressed gene clusters. The cumulative mRNAs of the differentially regulated DPGs, phase-I and -II enzymes, as well as efflux transporters were all up-regulated by both PCN and TCPOBOPOP, whereas the cumulative mRNAs of the uptake transporters were down-regulated only by TCPOBOP. The absolute mRNA abundance in control and receptor-activated conditions was examined in each DPG category to predict the contribution of specific DPG genes in the PXR/CAR-mediated pharmacokinetic responses. The preferable differential regulation by TCPOBOP in the

A Unique Mutation in a MYB Gene Cosegregates with the Nectarine Phenotype in Peach

PubMed Central

Dondini, Luca; Pacheco, Igor; Dettori, Maria Teresa; Gazza, Laura; Scalabrin, Simone; Strozzi, Francesco; Tartarini, Stefano; Bassi, Daniele; Verde, Ignazio; Rossini, Laura

2014-01-01

Nectarines play a key role in peach industry; the fuzzless skin has implications for consumer acceptance. The peach/nectarine (G/g) trait was described as monogenic and previously mapped on chromosome 5. Here, the position of the G locus was delimited within a 1.1 cM interval (635 kb) based on linkage analysis of an F2 progeny from the cross ‘Contender’ (C, peach) x ‘Ambra’ (A, nectarine). Careful inspection of the genes annotated in the corresponding genomic sequence (Peach v1.0), coupled with variant discovery, led to the identification of MYB gene PpeMYB25 as a candidate for trichome formation on fruit skin. Analysis of genomic re-sequencing data from five peach/nectarine accessions pointed to the insertion of a LTR retroelement in exon 3 of the PpeMYB25 gene as the cause of the recessive glabrous phenotype. A functional marker (indelG) developed on the LTR insertion cosegregated with the trait in the CxA F2 progeny and was validated on a broad panel of genotypes, including all known putative donors of the nectarine trait. This marker was shown to efficiently discriminate between peach and nectarine plants, indicating that a unique mutational event gave rise to the nectarine trait and providing a useful diagnostic tool for early seedling selection in peach breeding programs. PMID:24595269

Genome-wide gene expression effects in B6C3F1 mouse intestinal epithelia following 7 and 90 days of exposure to hexavalent chromium in drinking water

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

Kopec, Anna K.; Kim, Suntae; Forgacs, Agnes L.

2012-02-15

Chronic administration of high doses of hexavalent chromium [Cr(VI)] as sodium dichromate dihydrate (SDD) elicits alimentary cancers in mice. To further elucidate key events underlying tumor formation, a 90-day drinking water study was conducted in B6C3F1 mice. Differential gene expression was examined in duodenal and jejunal epithelial samples following 7 or 90 days of exposure to 0, 0.3, 4, 14, 60, 170 or 520 mg/L SDD in drinking water. Genome-wide microarray analyses identified 6562 duodenal and 4448 jejunal unique differentially expressed genes at day 8, and 4630 and 4845 unique changes, respectively, in the duodenum and jejunum at day 91.more » Comparative analysis identified significant overlap in duodenal and jejunal differential gene expression. Automated dose–response modeling identified > 80% of the differentially expressed genes exhibited sigmoidal dose–response curves with EC{sub 50} values ranging from 10 to 100 mg/L SDD. Only 16 genes satisfying the dose-dependent differential expression criteria had EC{sub 50} values < 10 mg/L SDD, 3 of which were regulated by Nrf2, suggesting oxidative stress in response to SDD at low concentrations. Analyses of differentially expressed genes identified over-represented functions associated with oxidative stress, cell cycle, lipid metabolism, and immune responses consistent with the reported effects on redox status and histopathology at corresponding SDD drinking water concentrations. Collectively, these data are consistent with a mode of action involving oxidative stress and cytotoxicity as early key events. This suggests that the tumorigenic effects of chronic Cr(VI) oral exposure likely require chronic tissue damage and compensatory epithelial cell proliferation. Highlights: ► Mouse small intestine gene expression is highly responsive to hexavalent chromium [Cr(VI)]. ► Cr(VI) elicits more differential gene expression after 7 days of exposure than 90 days of exposure. ► Oral exposure to Cr(VI) leads to

Identification of a precursor genomic segment that provided a sequence unique to glycophorin B and E genes

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

Onda, M.; Kudo, S.; Fukuda, M.

Human glycophorin A, B, and E (GPA, GPB, and GPE) genes belong to a gene family located at the long arm of chromosome 4. These three genes are homologous from the 5'-flanking sequence to the Alu sequence, which is 1 kb downstream from the exon encoding the transmembrane domain. Analysis of the Alu sequence and flanking direct repeat sequences suggested that the GPA gene most closely resembles the ancestral gene, whereas the GPB and GPE gene arose by homologous recombination within the Alu sequence, acquiring 3' sequences from an unrelated precursor genomic segment. Here the authors describe the identification ofmore » this putative precursor genomic segment. A human genomic library was screened by using the sequence of the 3' region of the GPB gene as a probe. The genomic clones isolated were found to contain an Alu sequence that appeared to be involved in the recombination. Downstream from the Alu sequence, the nucleotide sequence of the precursor genomic segment is almost identical to that of the GPB or GPE gene. In contrast, the upstream sequence of the genomic segment differs entirely from that of the GPA, GPB, and GPE genes. Conservation of the direct repeats flanking the Alu sequence of the genomic segment strongly suggests that the sequence of this genomic segment has been maintained during evolution. This identified genomic segment was found to reside downstream from the GPA gene by both gene mapping and in situ chromosomal localization. The precursor genomic segment was also identified in the orangutan genome, which is known to lack GPB and GPE genes. These results indicate that one of the duplicated ancestral glycophorin genes acquired a unique 3' sequence by unequal crossing-over through its Alu sequence and the further downstream Alu sequence present in the duplicated gene. Further duplication and divergence of this gene yielded the GPB and GPE genes. 37 refs., 5 figs.« less

Unique core genomes of the bacterial family vibrionaceae: insights into niche adaptation and speciation.

PubMed

Kahlke, Tim; Goesmann, Alexander; Hjerde, Erik; Willassen, Nils Peder; Haugen, Peik

2012-05-10

The criteria for defining bacterial species and even the concept of bacterial species itself are under debate, and the discussion is apparently intensifying as more genome sequence data is becoming available. However, it is still unclear how the new advances in genomics should be used most efficiently to address this question. In this study we identify genes that are common to any group of genomes in our dataset, to determine whether genes specific to a particular taxon exist and to investigate their potential role in adaptation of bacteria to their specific niche. These genes were named unique core genes. Additionally, we investigate the existence and importance of unique core genes that are found in isolates of phylogenetically non-coherent groups. These groups of isolates, that share a genetic feature without sharing a closest common ancestor, are termed genophyletic groups. The bacterial family Vibrionaceae was used as the model, and we compiled and compared genome sequences of 64 different isolates. Using the software orthoMCL we determined clusters of homologous genes among the investigated genome sequences. We used multilocus sequence analysis to build a host phylogeny and mapped the numbers of unique core genes of all distinct groups of isolates onto the tree. The results show that unique core genes are more likely to be found in monophyletic groups of isolates. Genophyletic groups of isolates, in contrast, are less common especially for large groups of isolate. The subsequent annotation of unique core genes that are present in genophyletic groups indicate a high degree of horizontally transferred genes. Finally, the annotation of the unique core genes of Vibrio cholerae revealed genes involved in aerotaxis and biosynthesis of the iron-chelator vibriobactin. The presented work indicates that genes specific for any taxon inside the bacterial family Vibrionaceae exist. These unique core genes encode conserved metabolic functions that can shed light on the

Cloning and characterization of mouse extracellular-signal-regulated protein kinase 3 as a unique gene product of 100 kDa.

PubMed

Turgeon, B; Saba-El-Leil, M K; Meloche, S

2000-02-15

MAP (mitogen-activated protein) kinases are a family of serine/threonine kinases that have a pivotal role in signal transduction. Here we report the cloning and characterization of a mouse homologue of extracellular-signal-regulated protein kinase (ERK)3. The mouse Erk3 cDNA encodes a predicted protein of 720 residues, which displays 94% identity with human ERK3. Transcription and translation of this cDNA in vitro generates a 100 kDa protein similar to the human gene product ERK3. Immunoblot analysis with an antibody raised against a unique sequence of ERK3 also recognizes a 100 kDa protein in mouse tissues. A single transcript of Erk3 was detected in every adult mouse tissue examined, with the highest expression being found in the brain. Interestingly, expression of Erk3 mRNA is acutely regulated during mouse development, with a peak of expression observed at embryonic day 11. The mouse Erk3 gene was mapped to a single locus on central mouse chromosome 9, adjacent to the dilute mutation locus and in a region syntenic to human chromosome 15q21. Finally, we provide several lines of evidence to support the existence of a unique Erk3 gene product of 100 kDa in mammalian cells.

Genome-wide DNA methylation profile identified a unique set of differentially methylated immune genes in oral squamous cell carcinoma patients in India.

PubMed

Basu, Baidehi; Chakraborty, Joyeeta; Chandra, Aditi; Katarkar, Atul; Baldevbhai, Jadav Ritesh Kumar; Dhar Chowdhury, Debjit; Ray, Jay Gopal; Chaudhuri, Keya; Chatterjee, Raghunath

2017-01-01

Oral squamous cell carcinoma (OSCC) is one of the common malignancies in Southeast Asia. Epigenetic changes, mainly the altered DNA methylation, have been implicated in many cancers. Considering the varied environmental and genotoxic exposures among the Indian population, we conducted a genome-wide DNA methylation study on paired tumor and adjacent normal tissues of ten well-differentiated OSCC patients and validated in an additional 53 well-differentiated OSCC and adjacent normal samples. Genome-wide DNA methylation analysis identified several novel differentially methylated regions associated with OSCC. Hypermethylation is primarily enriched in the CpG-rich regions, while hypomethylation is mainly in the open sea. Distinct epigenetic drifts for hypo- and hypermethylation across CpG islands suggested independent mechanisms of hypo- and hypermethylation in OSCC development. Aberrant DNA methylation in the promoter regions are concomitant with gene expression. Hypomethylation of immune genes reflect the lymphocyte infiltration into the tumor microenvironment. Comparison of methylome data with 312 TCGA HNSCC samples identified a unique set of hypomethylated promoters among the OSCC patients in India. Pathway analysis of unique hypomethylated promoters indicated that the OSCC patients in India induce an anti-tumor T cell response, with mobilization of T lymphocytes in the neoplastic environment. Survival analysis of these epigenetically regulated immune genes suggested their prominent role in OSCC progression. Our study identified a unique set of hypomethylated regions, enriched in the promoters of immune response genes, and indicated the presence of a strong immune component in the tumor microenvironment. These methylation changes may serve as potential molecular markers to define risk and to monitor the prognosis of OSCC patients in India.

Elicitation of Unstated Needs

DTIC Science & Technology

2014-09-17

what you can about requirements for a next generation laptop for the Home User that • attracts new customers • leverages existing customer loyalty ...Training © 2014 Carnegie Mellon University Traditional Requirements Elicitation Approaches Interviews of customers /users to elicit problems and usage...needs Inventory of problem reporting systems harboring customer complaints Solicitation of specification from customers /users to build a system

Analysis of common deafness gene mutations in deaf people from unique ethnic groups in Gansu Province, China.

PubMed

Xu, Bai-Cheng; Bian, Pan-Pan; Liu, Xiao-Wen; Zhu, Yi-Ming; Yang, Xiao-Long; Ma, Jian-Li; Chen, Xing-Jian; Wang, Yan-Li; Guo, Yu-Fen

2014-09-01

The GJB2 gene mutation characteristic of Dongxiang was the interaction result of ethnic background and geographical environment, and Yugur exhibited the typical founder effect. The SLC26A4 gene mutation characteristic of Dongxiang was related to caucasian backgrounds and selection of purpose exons, i.e. ethnic background and the penetrance of ethnic specificity caused the low mtDNA1555A>G mutation frequency in Dongxiang. To determine the prevalence of GJB2 and SLC26A4 genes and mtDNA1555A>G mutations and analyze the ethnic specificity in the non-syndromic sensorineural hearing loss (NSHL) of unique ethnic groups in Gansu Province. Peripheral blood samples were obtained from Dongxiang, Yugur, Bonan, and ethnic Han groups with moderately severe to profound NSHL in Gansu Province. Bidirectional sequencing (or enzyme digestion) was applied to identify the sequence variations. The pathogenic allele frequency of the three gene mutations was different. The frequency of the GJB2 gene among the Dongxiang, Yugur, Bonan, and ethnic Han groups was 9.03%, 12.5%, 5.88%, and 12.17%, respectively. No difference was found between the ethnic groups. The frequencies of the SLC26A4 genes were 3.23%, 8.33%, 0%, and 9.81%, respectively. The mutation frequency of mtDNA1555A>G was 0%, 0%, 0%, and 6.03%, respectively. No difference was found between the ethnic groups, except for the Dongxiang and ethnic Han groups, both in SLC26A4 gene and mtDNA1555A>G.

The Complete Mitochondrial Genome and Novel Gene Arrangement of the Unique-Headed Bug Stenopirates sp. (Hemiptera: Enicocephalidae)

PubMed Central

Li, Hu; Liu, Hui; Shi, Aimin; Štys, Pavel; Zhou, Xuguo; Cai, Wanzhi

2012-01-01

Many of true bugs are important insect pests to cultivated crops and some are important vectors of human diseases, but few cladistic analyses have addressed relationships among the seven infraorders of Heteroptera. The Enicocephalomorpha and Nepomorpha are consider the basal groups of Heteroptera, but the basal-most lineage remains unresolved. Here we report the mitochondrial genome of the unique-headed bug Stenopirates sp., the first mitochondrial genome sequenced from Enicocephalomorpha. The Stenopirates sp. mitochondrial genome is a typical circular DNA molecule of 15, 384 bp in length, and contains 37 genes and a large non-coding fragment. The gene order differs substantially from other known insect mitochondrial genomes, with rearrangements of both tRNA genes and protein-coding genes. The overall AT content (82.5%) of Stenopirates sp. is the highest among all the known heteropteran mitochondrial genomes. The strand bias is consistent with other true bugs with negative GC-skew and positive AT-skew for the J-strand. The heteropteran mitochondrial atp8 exhibits the highest evolutionary rate, whereas cox1 appears to have the lowest rate. Furthermore, a negative correlation was observed between the variation of nucleotide substitutions and the GC content of each protein-coding gene. A microsatellite was identified in the putative control region. Finally, phylogenetic reconstruction suggests that Enicocephalomorpha is the sister group to all the remaining Heteroptera. PMID:22235294

LED Blue Light-induced changes in phenolics and ethylene in citrus fruit: Implication in elicited resistance against Penicillium digitatum infection.

PubMed

Ballester, Ana-Rosa; Lafuente, María T

2017-03-01

The objective was to investigate whether LED Blue Light (LBL) induces changes in phenolics and ethylene production of sweet oranges, and whether they participate in LBL-elicited resistance against the most important postharvest pathogen (Penicillium digitatum) of citrus fruit. The expression of relevant genes of the phenylpropanoid and ethylene biosynthetic pathways during elicitation of resistance was also determined. Different LBL (wavelength 450nm) quantum fluxes were used within the 60-630μmolm -2 s -1 range. The HPLC analysis showed that the most relevant increase in phenylpropanoids occurred in scoparone, which markedly increased 3days after exposing fruits to a very high quantum flux (630μmolm -2 s -1 ) for 18h. However, phenylpropanoids, including scoparone, were not critical factors in LBL-induced resistance. The genes involved in ethylene biosynthesis were differentially regulated by LBL. Ethylene is not involved in elicited resistance, although high LBL levels increased ethylene production in only 1h. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

An internal regulatory element controls troponin I gene expression.

PubMed Central

Yutzey, K E; Kline, R L; Konieczny, S F

1989-01-01

During skeletal myogenesis, approximately 20 contractile proteins and related gene products temporally accumulate as the cells fuse to form multinucleated muscle fibers. In most instances, the contractile protein genes are regulated transcriptionally, which suggests that a common molecular mechanism may coordinate the expression of this diverse and evolutionarily unrelated gene set. Recent studies have examined the muscle-specific cis-acting elements associated with numerous contractile protein genes. All of the identified regulatory elements are positioned in the 5'-flanking regions, usually within 1,500 base pairs of the transcription start site. Surprisingly, a DNA consensus sequence that is common to each contractile protein gene has not been identified. In contrast to the results of these earlier studies, we have found that the 5'-flanking region of the quail troponin I (TnI) gene is not sufficient to permit the normal myofiber transcriptional activation of the gene. Instead, the TnI gene utilizes a unique internal regulatory element that is responsible for the correct myofiber-specific expression pattern associated with the TnI gene. This is the first example in which a contractile protein gene has been shown to rely primarily on an internal regulatory element to elicit transcriptional activation during myogenesis. The diversity of regulatory elements associated with the contractile protein genes suggests that the temporal expression of the genes may involve individual cis-trans regulatory components specific for each gene. Images PMID:2725509

Seeking unique and common biological themes in multiple gene lists or datasets: pathway pattern extraction pipeline for pathway-level comparative analysis.

PubMed

Yi, Ming; Mudunuri, Uma; Che, Anney; Stephens, Robert M

2009-06-29

One of the challenges in the analysis of microarray data is to integrate and compare the selected (e.g., differential) gene lists from multiple experiments for common or unique underlying biological themes. A common way to approach this problem is to extract common genes from these gene lists and then subject these genes to enrichment analysis to reveal the underlying biology. However, the capacity of this approach is largely restricted by the limited number of common genes shared by datasets from multiple experiments, which could be caused by the complexity of the biological system itself. We now introduce a new Pathway Pattern Extraction Pipeline (PPEP), which extends the existing WPS application by providing a new pathway-level comparative analysis scheme. To facilitate comparing and correlating results from different studies and sources, PPEP contains new interfaces that allow evaluation of the pathway-level enrichment patterns across multiple gene lists. As an exploratory tool, this analysis pipeline may help reveal the underlying biological themes at both the pathway and gene levels. The analysis scheme provided by PPEP begins with multiple gene lists, which may be derived from different studies in terms of the biological contexts, applied technologies, or methodologies. These lists are then subjected to pathway-level comparative analysis for extraction of pathway-level patterns. This analysis pipeline helps to explore the commonality or uniqueness of these lists at the level of pathways or biological processes from different but relevant biological systems using a combination of statistical enrichment measurements, pathway-level pattern extraction, and graphical display of the relationships of genes and their associated pathways as Gene-Term Association Networks (GTANs) within the WPS platform. As a proof of concept, we have used the new method to analyze many datasets from our collaborators as well as some public microarray datasets. This tool provides a

An internal regulatory element controls troponin I gene expression

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

Yutzey, K.E.; Kline, R.L.; Konieczmy, S.F.

1989-04-01

During skeletal myogenesis, approximately 20 contractile proteins and related gene products temporally accumulate as the cells fuse to form multinucleated muscle fibers. In most instances, the contractile protein genes are regulated transcriptionally, which suggests that a common molecular mechanism may coordinate the expression of this diverse and evolutionarily unrelated gene set. Recent studies have examined the muscle-specific cis-acting elements associated with numerous contractile protein genes. All of the identified regulatory elements are positioned in the 5'-flanking regions, usually within 1,500 base pairs of the transcription start site. Surprisingly, a DNA consensus sequence that is common to each contractile protein genemore » has not been identified. In contrast to the results of these earlier studies, the authors have found that the 5'-flanking region of the quail troponin I (TnI) gene is not sufficient to permit the normal myofiber transcriptional activation of the gene. Instead, the TnI gene utilizes a unique internal regulatory element that is responsible for the correct myofiber-specific expression pattern associated with the TnI gene. This is the first example in which a contractile protein gene has been shown to rely primarily on an internal regulatory element to elicit transcriptional activation during myogenesis. The diversity of regulatory elements associated with the contractile protein genes suggests that the temporal expression of the genes may involve individual cis-trans regulatory components specific for each gene.« less

Deciphering a unique biotin scavenging pathway with redundant genes in the probiotic bacterium Lactococcus lactis

PubMed Central

Zhang, Huimin; Wang, Qingjing; Fisher, Derek J.; Cai, Mingzhu; Chakravartty, Vandana; Ye, Huiyan; Li, Ping; Solbiati, Jose O.; Feng, Youjun

2016-01-01

Biotin protein ligase (BPL) is widespread in the three domains of the life. The paradigm BPL is the Escherichia coli BirA protein, which also functions as a repressor for the biotin biosynthesis pathway. Here we report that Lactococcus lactis possesses two different orthologues of birA (birA1_LL and birA2_LL). Unlike the scenario in E. coli, L. lactis appears to be auxotrophic for biotin in that it lacks a full biotin biosynthesis pathway. In contrast, it retains two biotin transporter-encoding genes (bioY1_LL and bioY2_LL), suggesting the use of a scavenging strategy to obtain biotin from the environment. The in vivo function of the two L. lactis birA genes was judged by their abilities to complement the conditional lethal E. coli birA mutant. Thin-layer chromatography and mass spectroscopy assays demonstrated that these two recombinant BirA proteins catalyze the biotinylation reaction of the acceptor biotin carboxyl carrier protein (BCCP), through the expected biotinoyl-AMP intermediate. Gel shift assays were used to characterize bioY1_LL and BirA1_LL. We also determined the ability to uptake 3H-biotin by L. lactis. Taken together, our results deciphered a unique biotin scavenging pathway with redundant genes present in the probiotic bacterium L. lactis. PMID:27161258

Deciphering a unique biotin scavenging pathway with redundant genes in the probiotic bacterium Lactococcus lactis.

PubMed

Zhang, Huimin; Wang, Qingjing; Fisher, Derek J; Cai, Mingzhu; Chakravartty, Vandana; Ye, Huiyan; Li, Ping; Solbiati, Jose O; Feng, Youjun

2016-05-10

Biotin protein ligase (BPL) is widespread in the three domains of the life. The paradigm BPL is the Escherichia coli BirA protein, which also functions as a repressor for the biotin biosynthesis pathway. Here we report that Lactococcus lactis possesses two different orthologues of birA (birA1_LL and birA2_LL). Unlike the scenario in E. coli, L. lactis appears to be auxotrophic for biotin in that it lacks a full biotin biosynthesis pathway. In contrast, it retains two biotin transporter-encoding genes (bioY1_LL and bioY2_LL), suggesting the use of a scavenging strategy to obtain biotin from the environment. The in vivo function of the two L. lactis birA genes was judged by their abilities to complement the conditional lethal E. coli birA mutant. Thin-layer chromatography and mass spectroscopy assays demonstrated that these two recombinant BirA proteins catalyze the biotinylation reaction of the acceptor biotin carboxyl carrier protein (BCCP), through the expected biotinoyl-AMP intermediate. Gel shift assays were used to characterize bioY1_LL and BirA1_LL. We also determined the ability to uptake (3)H-biotin by L. lactis. Taken together, our results deciphered a unique biotin scavenging pathway with redundant genes present in the probiotic bacterium L. lactis.

Gene Expression Profile Analysis as a Prognostic Indicator of Normal Tissue Response to Simulated Space Radiations

NASA Technical Reports Server (NTRS)

Story, Michael; Stivers, David N.

2004-01-01

This project was funded as a pilot project to determine the feasibility of using gene expression profiles to characterize the response of human cells to exposure to particulate radiations such as those encountered in the spaceflight environment. We proposed to use microarray technology to examine the gene expression patterns of a bank of well-characterized human fibroblast cell cultures. These fibroblast cultures were derived from breast or head and neck cancer patients who exhibited normal, minimal, or severe normal tissue reactions following low LET radiation exposure via radiotherapy. Furthermore, determination of SF2 values from fibroblasts cultured from these individuals were predictive of risk for severe late reactions. We hypothesized that by determining the expression of thousands of genes we could identify gene expression patterns that reflect how normal tissues respond to high Z and energy (HZE) particles, that is, that there are molecular signatures for HZE exposures. We also hypothesized that individuals who are intrinsically radiosensitive may elicit a unique response. Because this was funded as a pilot project we focused our initial studies on logistics and appropriate experimental design, and then to test our hypothesis that there is a unique molecular response to specific particles, in this case C and Fe, for primary human skin fibroblasts.

Functions and Unique Diversity of Genes and Microorganisms Involved in Arsenite Oxidation from the Tailings of a Realgar Mine

PubMed Central

E, Guoji; Wang, Jianing; Wang, Nian; Chen, Xiaoming; Mu, Yao; Li, Hao; Yang, Ye; Liu, Yichen; Wang, Yanxin

2016-01-01

ABSTRACT The tailings of the Shimen realgar mine have unique geochemical features. Arsenite oxidation is one of the major biogeochemical processes that occurs in the tailings. However, little is known about the functional and molecular aspects of the microbial community involved in arsenite oxidation. Here, we fully explored the functional and molecular features of the microbial communities from the tailings of the Shimen realgar mine. We collected six samples of tailings from sites A, B, C, D, E, and F. Microcosm assays indicated that all of the six sites contain both chemoautotrophic and heterotrophic arsenite-oxidizing microorganisms; their activities differed considerably from each other. The microbial arsenite-oxidizing activities show a positive correlation with soluble arsenic concentrations. The microbial communities of the six sites contain 40 phyla of bacteria and 2 phyla of archaea that show extremely high diversity. Soluble arsenic, sulfate, pH, and total organic carbon (TOC) are the key environmental factors that shape the microbial communities. We further identified 114 unique arsenite oxidase genes from the samples; all of them code for new or new-type arsenite oxidases. We also isolated 10 novel arsenite oxidizers from the samples, of which 4 are chemoautotrophic and 6 are heterotrophic. These data highlight the unique diversities of the arsenite-oxidizing microorganisms and their oxidase genes from the tailings of the Shimen realgar mine. To the best of our knowledge, this is the first report describing the functional and molecular features of microbial communities from the tailings of a realgar mine. IMPORTANCE This study focused on the functional and molecular characterizations of microbial communities from the tailings of the Shimen realgar mine. We fully explored, for the first time, the arsenite-oxidizing activities and the functional gene diversities of microorganisms from the tailings, as well as the correlation of the microbial activities

Functions and Unique Diversity of Genes and Microorganisms Involved in Arsenite Oxidation from the Tailings of a Realgar Mine.

PubMed

Zeng, Xian-Chun; E, Guoji; Wang, Jianing; Wang, Nian; Chen, Xiaoming; Mu, Yao; Li, Hao; Yang, Ye; Liu, Yichen; Wang, Yanxin

2016-12-15

The tailings of the Shimen realgar mine have unique geochemical features. Arsenite oxidation is one of the major biogeochemical processes that occurs in the tailings. However, little is known about the functional and molecular aspects of the microbial community involved in arsenite oxidation. Here, we fully explored the functional and molecular features of the microbial communities from the tailings of the Shimen realgar mine. We collected six samples of tailings from sites A, B, C, D, E, and F. Microcosm assays indicated that all of the six sites contain both chemoautotrophic and heterotrophic arsenite-oxidizing microorganisms; their activities differed considerably from each other. The microbial arsenite-oxidizing activities show a positive correlation with soluble arsenic concentrations. The microbial communities of the six sites contain 40 phyla of bacteria and 2 phyla of archaea that show extremely high diversity. Soluble arsenic, sulfate, pH, and total organic carbon (TOC) are the key environmental factors that shape the microbial communities. We further identified 114 unique arsenite oxidase genes from the samples; all of them code for new or new-type arsenite oxidases. We also isolated 10 novel arsenite oxidizers from the samples, of which 4 are chemoautotrophic and 6 are heterotrophic. These data highlight the unique diversities of the arsenite-oxidizing microorganisms and their oxidase genes from the tailings of the Shimen realgar mine. To the best of our knowledge, this is the first report describing the functional and molecular features of microbial communities from the tailings of a realgar mine. This study focused on the functional and molecular characterizations of microbial communities from the tailings of the Shimen realgar mine. We fully explored, for the first time, the arsenite-oxidizing activities and the functional gene diversities of microorganisms from the tailings, as well as the correlation of the microbial activities/diversities with

Unique and redundant functional domains of APETALA1 and CAULIFLOWER, two recently duplicated Arabidopsis thaliana floral MADS-box genes.

PubMed

Alvarez-Buylla, Elena R; García-Ponce, Berenice; Garay-Arroyo, Adriana

2006-01-01

APETALA1 (AP1) and CAULIFLOWER (CAL) are closely related MADS box genes that are partially redundant during Arabidopsis thaliana floral meristem determination. AP1 is able to fully substitute for CAL functions, but not vice versa, and AP1 has unique sepal and petal identity specification functions. In this study, the unique and redundant functions of these two genes has been mapped to the four protein domains that characterize type-II MADS-domain proteins by expressing all 15 chimeric combinations of AP1 and CAL cDNA regions under control of the AP1 promoter in ap1-1 loss-of-function plants. The "in vivo" function of these chimeric genes was analysed in Arabidopsis plants by expressing the chimeras. Rescue of flower meristem and sepal/petal identities was scored in single and multiple insert homozygous transgenic lines. Using these chimeric lines, it was found that distinct residues of the AP1 K domain not shared by the same CAL domain are necessary and sufficient for complete recovery of floral meristem identity, in the context of the CAL protein sequence, while both AP1 COOH and K domains are indispensable for complete rescue of sepal identity. By contrast, either one of these two AP1 domains is necessary and sufficient for complete petal identity recovery. It was also found that there were positive and negative synergies among protein domains and their combinations, and that multiple-insert lines showed relatively better rescue than equivalent single-insert lines. Finally, several lines had flowers with extra sepals and petals suggesting that chimeric proteins yield abnormal transcriptional complexes that may alter the expression or regulation of genes that control floral organ number under normal conditions.

Complexities of gene expression patterns in natural populations of an extremophile fish (Poecilia mexicana, Poeciliidae)

PubMed Central

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

2017-01-01

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 (H2S) 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 H2S and darkness coincide. Functional annotations of differentially expressed genes provide a springboard for investigating physiological mechanisms putatively underlying adaptation to extreme environments. PMID:28598519

Giraffe genome sequence reveals clues to its unique morphology and physiology

PubMed Central

Agaba, Morris; Ishengoma, Edson; Miller, Webb C.; McGrath, Barbara C.; Hudson, Chelsea N.; Bedoya Reina, Oscar C.; Ratan, Aakrosh; Burhans, Rico; Chikhi, Rayan; Medvedev, Paul; Praul, Craig A.; Wu-Cavener, Lan; Wood, Brendan; Robertson, Heather; Penfold, Linda; Cavener, Douglas R.

2016-01-01

The origins of giraffe's imposing stature and associated cardiovascular adaptations are unknown. Okapi, which lacks these unique features, is giraffe's closest relative and provides a useful comparison, to identify genetic variation underlying giraffe's long neck and cardiovascular system. The genomes of giraffe and okapi were sequenced, and through comparative analyses genes and pathways were identified that exhibit unique genetic changes and likely contribute to giraffe's unique features. Some of these genes are in the HOX, NOTCH and FGF signalling pathways, which regulate both skeletal and cardiovascular development, suggesting that giraffe's stature and cardiovascular adaptations evolved in parallel through changes in a small number of genes. Mitochondrial metabolism and volatile fatty acids transport genes are also evolutionarily diverged in giraffe and may be related to its unusual diet that includes toxic plants. Unexpectedly, substantial evolutionary changes have occurred in giraffe and okapi in double-strand break repair and centrosome functions. PMID:27187213

Gustatory stimuli representing different perceptual qualities elicit distinct patterns of neuropeptide secretion from taste buds.

PubMed

Geraedts, Maartje C P; Munger, Steven D

2013-04-24

Taste stimuli that evoke different perceptual qualities (e.g., sweet, umami, bitter, sour, salty) are detected by dedicated subpopulations of taste bud cells that use distinct combinations of sensory receptors and transduction molecules. Here, we report that taste stimuli also elicit unique patterns of neuropeptide secretion from taste buds that are correlated with those perceptual qualities. We measured tastant-dependent secretion of glucagon-like peptide-1 (GLP-1), glucagon, and neuropeptide Y (NPY) from circumvallate papillae of Tas1r3(+/+), Tas1r3(+/-) and Tas1r3 (-/-) mice. Isolated tongue epithelia were mounted in modified Ussing chambers, permitting apical stimulation of taste buds; secreted peptides were collected from the basal side and measured by specific ELISAs. Appetitive stimuli (sweet: glucose, sucralose; umami: monosodium glutamate; polysaccharide: Polycose) elicited GLP-1 and NPY secretion and inhibited basal glucagon secretion. Sweet and umami stimuli were ineffective in Tas1r3(-/-) mice, indicating an obligatory role for the T1R3 subunit common to the sweet and umami taste receptors. Polycose responses were unaffected by T1R3 deletion, consistent with the presence of a distinct polysaccharide taste receptor. The effects of sweet stimuli on peptide secretion also required the closing of ATP-sensitive K(+) (KATP) channels, as the KATP channel activator diazoxide inhibited the effects of glucose and sucralose on both GLP-1 and glucagon release. Both sour citric acid and salty NaCl increased NPY secretion but had no effects on GLP-1 or glucagon. Bitter denatonium showed no effects on these peptides. Together, these results suggest that taste stimuli of different perceptual qualities elicit unique patterns of neuropeptide secretion from taste buds.

Identification of Entamoeba polecki with Unique 18S rRNA Gene Sequences from Celebes Crested Macaques and Pigs in Tangkoko Nature Reserve, North Sulawesi, Indonesia.

PubMed

Tuda, Josef; Feng, Meng; Imada, Mihoko; Kobayashi, Seiki; Cheng, Xunjia; Tachibana, Hiroshi

2016-09-01

Unique species of macaques are distributed across Sulawesi Island, Indonesia, and the details of Entamoeba infections in these macaques are unknown. A total of 77 stool samples from Celebes crested macaques (Macaca nigra) and 14 stool samples from pigs were collected in Tangkoko Nature Reserve, North Sulawesi, and the prevalence of Entamoeba infection was examined by PCR. Entamoeba polecki was detected in 97% of the macaques and all of the pigs, but no other Entamoeba species were found. The nucleotide sequence of the 18S rRNA gene in E. polecki from M. nigra was unique and showed highest similarity with E. polecki subtype (ST) 4. This is the first case of identification of E. polecki ST4 from wild nonhuman primates. The sequence of the 18S rRNA gene in E. polecki from pigs was also unique and showed highest similarity with E. polecki ST1. These results suggest that the diversity of the 18S rRNA gene in E. polecki is associated with differences in host species and geographic localization, and that there has been no transmission of E. polecki between macaques and pigs in the study area. © 2016 The Author(s) Journal of Eukaryotic Microbiology © 2016 International Society of Protistologists.

Unique Physiological and Transcriptional Shifts under Combinations of Salinity, Drought, and Heat.

PubMed

Shaar-Moshe, Lidor; Blumwald, Eduardo; Peleg, Zvi

2017-05-01

Climate-change-driven stresses such as extreme temperatures, water deficit, and ion imbalance are projected to exacerbate and jeopardize global food security. Under field conditions, these stresses usually occur simultaneously and cause damages that exceed single stresses. Here, we investigated the transcriptional patterns and morpho-physiological acclimations of Brachypodium dystachion to single salinity, drought, and heat stresses, as well as their double and triple stress combinations. Hierarchical clustering analysis of morpho-physiological acclimations showed that several traits exhibited a gradually aggravating effect as plants were exposed to combined stresses. On the other hand, other morphological traits were dominated by salinity, while some physiological traits were shaped by heat stress. Response patterns of differentially expressed genes, under single and combined stresses (i.e. common stress genes), were maintained only among 37% of the genes, indicating a limited expression consistency among partially overlapping stresses. A comparison between common stress genes and genes that were uniquely expressed only under combined stresses (i.e. combination unique genes) revealed a significant shift from increased intensity to antagonistic responses, respectively. The different transcriptional signatures imply an alteration in the mode of action under combined stresses and limited ability to predict plant responses as different stresses are combined. Coexpression analysis coupled with enrichment analysis revealed that each gene subset was enriched with different biological processes. Common stress genes were enriched with known stress response pathways, while combination unique-genes were enriched with unique processes and genes with unknown functions that hold the potential to improve stress tolerance and enhance cereal productivity under suboptimal field conditions. © 2017 American Society of Plant Biologists. All Rights Reserved.

Unique morphological changes in plant pathogenic phytoplasma-infected petunia flowers are related to transcriptional regulation of floral homeotic genes in an organ-specific manner.

PubMed

Himeno, Misako; Neriya, Yutaro; Minato, Nami; Miura, Chihiro; Sugawara, Kyoko; Ishii, Yoshiko; Yamaji, Yasuyuki; Kakizawa, Shigeyuki; Oshima, Kenro; Namba, Shigetou

2011-09-01

Abnormal flowers are often induced by infection of certain plant pathogens, e.g. phytoplasma, but the molecular mechanisms underlying these malformations have remained poorly understood. Here, we show that infection with OY-W phytoplasma (Candidatus Phytoplasma asteris, onion yellows phytoplasma strain, line OY-W) affects the expression of the floral homeotic genes of petunia plants in an organ-specific manner. Upon infection with OY-W phytoplasma, floral morphological changes, including conversion to leaf-like structures, were observed in sepals, petals and pistils, but not in stamens. As the expression levels of homeotic genes differ greatly between floral organs, we examined the expression levels of homeotic genes in each floral organ infected by OY-W phytoplasma, compared with healthy plants. The expression levels of several homeotic genes required for organ development, such as PFG, PhGLO1 and FBP7, were significantly downregulated by the phytoplasma infection in floral organs, except the stamens, suggesting that the unique morphological changes caused by the phytoplasma infection might result from the significant decrease in expression of some crucial homeotic genes. Moreover, the expression levels of TER, ALF and DOT genes, which are known to participate in floral meristem identity, were significantly downregulated in the phytoplasma-infected petunia meristems, implying that phytoplasma would affect an upstream signaling pathway of floral meristem identity. Our results suggest that phytoplasma infection may have complex effects on floral development, resulting in the unique phenotypes that were clearly distinct from the mutant flower phenotypes produced by the knock-out or the overexpression of certain homeotic genes. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

Integration of Genome-Wide Computation DRE Search, AhR ChIP-chip and Gene Expression Analyses of TCDD-Elicited Responses in the Mouse Liver

PubMed Central

2011-01-01

Background The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor (TF) that mediates responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Integration of TCDD-induced genome-wide AhR enrichment, differential gene expression and computational dioxin response element (DRE) analyses further elucidate the hepatic AhR regulatory network. Results Global ChIP-chip and gene expression analyses were performed on hepatic tissue from immature ovariectomized mice orally gavaged with 30 μg/kg TCDD. ChIP-chip analysis identified 14,446 and 974 AhR enriched regions (1% false discovery rate) at 2 and 24 hrs, respectively. Enrichment density was greatest in the proximal promoter, and more specifically, within ± 1.5 kb of a transcriptional start site (TSS). AhR enrichment also occurred distal to a TSS (e.g. intergenic DNA and 3' UTR), extending the potential gene expression regulatory roles of the AhR. Although TF binding site analyses identified over-represented DRE sequences within enriched regions, approximately 50% of all AhR enriched regions lacked a DRE core (5'-GCGTG-3'). Microarray analysis identified 1,896 number of TCDD-responsive genes (|fold change| ≥ 1.5, P1(t) > 0.999). Integrating this gene expression data with our ChIP-chip and DRE analyses only identified 625 differentially expressed genes that involved an AhR interaction at a DRE. Functional annotation analysis of differentially regulated genes associated with AhR enrichment identified overrepresented processes related to fatty acid and lipid metabolism and transport, and xenobiotic metabolism, which are consistent with TCDD-elicited steatosis in the mouse liver. Conclusions Details of the AhR regulatory network have been expanded to include AhR-DNA interactions within intragenic and intergenic genomic regions. Moreover, the AhR can interact with DNA independent of a DRE core suggesting there are alternative mechanisms of AhR-mediated gene regulation. PMID:21762485

Patients experiencing statin-induced myalgia exhibit a unique program of skeletal muscle gene expression following statin re-challenge

PubMed Central

Majumdar, Gipsy; Mozhui, Khyobeni; Gerling, Ivan C.; Vera, Santiago R.; Fish-Trotter, Hannah; Williams, Robert W.; Childress, Richard D.

2017-01-01

Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate changes in gene expression associated with statin myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin myalgia who were undergoing statin re-challenge (cases) versus those of statin-tolerant controls. A robust separation of case and control cohorts was revealed by Principal Component Analysis of differentially expressed genes (DEGs). To identify putative gene expression and metabolic pathways that may be perturbed in skeletal muscles of patients with statin myalgia, we subjected DEGs to Ingenuity Pathways (IPA) and DAVID (Database for Annotation, Visualization and Integrated Discovery) analyses. The most prominent pathways altered by statins included cellular stress, apoptosis, cell senescence and DNA repair (TP53, BARD1, Mre11 and RAD51); activation of pro-inflammatory immune response (CXCL12, CST5, POU2F1); protein catabolism, cholesterol biosynthesis, protein prenylation and RAS-GTPase activation (FDFT1, LSS, TP53, UBD, ATF2, H-ras). Based on these data we tentatively conclude that persistent myalgia in response to statins may emanate from cellular stress underpinned by mechanisms of post-inflammatory repair and regeneration. We also posit that this subset of individuals is genetically predisposed to eliciting altered statin metabolism and/or increased end-organ susceptibility that lead to a range of statin-induced myopathies. This mechanistic scenario is further bolstered by the discovery that a number of single nucleotide

Patients experiencing statin-induced myalgia exhibit a unique program of skeletal muscle gene expression following statin re-challenge.

PubMed

Elam, Marshall B; Majumdar, Gipsy; Mozhui, Khyobeni; Gerling, Ivan C; Vera, Santiago R; Fish-Trotter, Hannah; Williams, Robert W; Childress, Richard D; Raghow, Rajendra

2017-01-01

Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate changes in gene expression associated with statin myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin myalgia who were undergoing statin re-challenge (cases) versus those of statin-tolerant controls. A robust separation of case and control cohorts was revealed by Principal Component Analysis of differentially expressed genes (DEGs). To identify putative gene expression and metabolic pathways that may be perturbed in skeletal muscles of patients with statin myalgia, we subjected DEGs to Ingenuity Pathways (IPA) and DAVID (Database for Annotation, Visualization and Integrated Discovery) analyses. The most prominent pathways altered by statins included cellular stress, apoptosis, cell senescence and DNA repair (TP53, BARD1, Mre11 and RAD51); activation of pro-inflammatory immune response (CXCL12, CST5, POU2F1); protein catabolism, cholesterol biosynthesis, protein prenylation and RAS-GTPase activation (FDFT1, LSS, TP53, UBD, ATF2, H-ras). Based on these data we tentatively conclude that persistent myalgia in response to statins may emanate from cellular stress underpinned by mechanisms of post-inflammatory repair and regeneration. We also posit that this subset of individuals is genetically predisposed to eliciting altered statin metabolism and/or increased end-organ susceptibility that lead to a range of statin-induced myopathies. This mechanistic scenario is further bolstered by the discovery that a number of single nucleotide

Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein

PubMed Central

Hashimoto, Takuma; Horikawa, Daiki D.; Saito, Yuki; Kuwahara, Hirokazu; Kozuka-Hata, Hiroko; Shin-I, Tadasu; Minakuchi, Yohei; Ohishi, Kazuko; Motoyama, Ayuko; Aizu, Tomoyuki; Enomoto, Atsushi; Kondo, Koyuki; Tanaka, Sae; Hara, Yuichiro; Koshikawa, Shigeyuki; Sagara, Hiroshi; Miura, Toru; Yokobori, Shin-ichi; Miyagawa, Kiyoshi; Suzuki, Yutaka; Kubo, Takeo; Oyama, Masaaki; Kohara, Yuji; Fujiyama, Asao; Arakawa, Kazuharu; Katayama, Toshiaki; Toyoda, Atsushi; Kunieda, Takekazu

2016-01-01

Tardigrades, also known as water bears, are small aquatic animals. Some tardigrade species tolerate almost complete dehydration and exhibit extraordinary tolerance to various physical extremes in the dehydrated state. Here we determine a high-quality genome sequence of Ramazzottius varieornatus, one of the most stress-tolerant tardigrade species. Precise gene repertoire analyses reveal the presence of a small proportion (1.2% or less) of putative foreign genes, loss of gene pathways that promote stress damage, expansion of gene families related to ameliorating damage, and evolution and high expression of novel tardigrade-unique proteins. Minor changes in the gene expression profiles during dehydration and rehydration suggest constitutive expression of tolerance-related genes. Using human cultured cells, we demonstrate that a tardigrade-unique DNA-associating protein suppresses X-ray-induced DNA damage by ∼40% and improves radiotolerance. These findings indicate the relevance of tardigrade-unique proteins to tolerability and tardigrades could be a bountiful source of new protection genes and mechanisms. PMID:27649274

Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein.

PubMed

Hashimoto, Takuma; Horikawa, Daiki D; Saito, Yuki; Kuwahara, Hirokazu; Kozuka-Hata, Hiroko; Shin-I, Tadasu; Minakuchi, Yohei; Ohishi, Kazuko; Motoyama, Ayuko; Aizu, Tomoyuki; Enomoto, Atsushi; Kondo, Koyuki; Tanaka, Sae; Hara, Yuichiro; Koshikawa, Shigeyuki; Sagara, Hiroshi; Miura, Toru; Yokobori, Shin-Ichi; Miyagawa, Kiyoshi; Suzuki, Yutaka; Kubo, Takeo; Oyama, Masaaki; Kohara, Yuji; Fujiyama, Asao; Arakawa, Kazuharu; Katayama, Toshiaki; Toyoda, Atsushi; Kunieda, Takekazu

2016-09-20

Tardigrades, also known as water bears, are small aquatic animals. Some tardigrade species tolerate almost complete dehydration and exhibit extraordinary tolerance to various physical extremes in the dehydrated state. Here we determine a high-quality genome sequence of Ramazzottius varieornatus, one of the most stress-tolerant tardigrade species. Precise gene repertoire analyses reveal the presence of a small proportion (1.2% or less) of putative foreign genes, loss of gene pathways that promote stress damage, expansion of gene families related to ameliorating damage, and evolution and high expression of novel tardigrade-unique proteins. Minor changes in the gene expression profiles during dehydration and rehydration suggest constitutive expression of tolerance-related genes. Using human cultured cells, we demonstrate that a tardigrade-unique DNA-associating protein suppresses X-ray-induced DNA damage by ∼40% and improves radiotolerance. These findings indicate the relevance of tardigrade-unique proteins to tolerability and tardigrades could be a bountiful source of new protection genes and mechanisms.

Medroxyprogesterone acetate-treated human, primary endometrial epithelial cells reveal unique gene expression signature linked to innate immunity and HIV-1 susceptibility.

PubMed

Woods, Matthew W; Zahoor, Muhammad Atif; Dizzell, Sara; Verschoor, Chris P; Kaushic, Charu

2018-01-01

Medroxyprogesterone acetate (MPA), a progestin-based hormonal contraceptive designed to mimic progesterone, has been linked to increased human immunodeficiency virus (HIV-1) susceptibility. Genital epithelial cells (GECs) form the mucosal lining of the female genital tract (FGT) and provide the first line of protection against HIV-1. The impact of endogenous sex hormones or MPA on the gene expression profile of GECs has not been comprehensively documented. Using microarray analysis, we characterized the transcriptional profile of primary endometrial epithelial cells grown in physiological levels of E2, P4, and MPA. Each hormone treatment altered the gene expression profile of GECs in a unique manner. Interestingly, although MPA is a progestogen, the gene expression profile induced by it was distinct from P4. MPA increased gene expression of genes related to inflammation and cholesterol synthesis linked to innate immunity and HIV-1 susceptibility. The analysis of gene expression profiles provides insights into the effects of sex hormones and MPA on GECs and allows us to posit possible mechanisms of the MPA-mediated increase in HIV-1 acquisition. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Unique disease heritage of the Dutch-German Mennonite population.

PubMed

Orton, Noelle C; Innes, A Micheil; Chudley, Albert E; Bech-Hansen, N Torben

2008-04-15

The Dutch-German Mennonites are a religious isolate with foundational roots in the 16th century. A tradition of endogamy, large families, detailed genealogical records, and a unique disease history all contribute to making this a valuable population for genetic studies. Such studies in the Dutch-German Mennonite population have already contributed to the identification of the causative genes in several conditions such as the incomplete form of X-linked congenital stationary night blindness (CSNB2; previously iCSNB) and hypophosphatasia (HOPS), as well as the discovery of founder mutations within established disease genes (MYBPC1, CYP17alpha). The Dutch-German Mennonite population provides a strong resource for gene discovery and could lead to the identification of additional disease genes with relevance to the general population. In addition, further research developments should enhance delivery of clinical genetic services to this unique community. In the current review we discuss 31 genetic conditions, including 17 with identified gene mutations, within the Dutch-German Mennonite population. Copyright 2008 Wiley-Liss, Inc.

Unique semantic space in the brain of each beholder predicts perceived similarity

PubMed Central

Charest, Ian; Kievit, Rogier A.; Schmitz, Taylor W.; Deca, Diana; Kriegeskorte, Nikolaus

2014-01-01

The unique way in which each of us perceives the world must arise from our brain representations. If brain imaging could reveal an individual’s unique mental representation, it could help us understand the biological substrate of our individual experiential worlds in mental health and disease. However, imaging studies of object vision have focused on commonalities between individuals rather than individual differences and on category averages rather than representations of particular objects. Here we investigate the individually unique component of brain representations of particular objects with functional MRI (fMRI). Subjects were presented with unfamiliar and personally meaningful object images while we measured their brain activity on two separate days. We characterized the representational geometry by the dissimilarity matrix of activity patterns elicited by particular object images. The representational geometry remained stable across scanning days and was unique in each individual in early visual cortex and human inferior temporal cortex (hIT). The hIT representation predicted perceived similarity as reflected in dissimilarity judgments. Importantly, hIT predicted the individually unique component of the judgments when the objects were personally meaningful. Our results suggest that hIT brain representational idiosyncrasies accessible to fMRI are expressed in an individual's perceptual judgments. The unique way each of us perceives the world thus might reflect the individually unique representation in high-level visual areas. PMID:25246586

Freeze or flee? Negative stimuli elicit selective responding.

PubMed

Estes, Zachary; Verges, Michelle

2008-08-01

Humans preferentially attend to negative stimuli. A consequence of this automatic vigilance for negative valence is that negative words elicit slower responses than neutral or positive words on a host of cognitive tasks. Some researchers have speculated that negative stimuli elicit a general suppression of motor activity, akin to the freezing response exhibited by animals under threat. Alternatively, we suggest that negative stimuli only elicit slowed responding on tasks for which stimulus valence is irrelevant for responding. To discriminate between these motor suppression and response-relevance hypotheses, we elicited both lexical decisions and valence judgments of negative words and positive words. Relative to positive words (e.g., kitten), negative words (e.g., spider) elicited slower lexical decisions but faster valence judgments. Results therefore indicate that negative stimuli do not cause a generalized motor suppression. Rather, negative stimuli elicit selective responding, with faster responses on tasks for which stimulus valence is response-relevant.

Bacterial avirulence genes.

PubMed

Leach, J E; White, F F

1996-01-01

Although more than 30 bacterial avirulence genes have been cloned and characterized, the function of the gene products in the elictitation of resistance is unknown in all cases but one. The product of avrD from Pseudomonas syringae pv. glycinea likely functions indirectly to elicit resistance in soybean, that is, evidence suggests the gene product is an enzyme involved in elicitor production. In most if not all cases, bacterial avirulence gene function is dependent on interactions with the hypersensitive response and pathogenicity (hrp) genes. Many hrp genes are similar to genes involved in delivery of pathogenicity factors in mammalian bacterial pathogens. Thus, analogies between mammalian and plant pathogens may provide needed clues to elucidate how virulence gene products control induction of resistance.

L-Amino Acids Elicit Diverse Response Patterns in Taste Sensory Cells: A Role for Multiple Receptors

PubMed Central

Pal Choudhuri, Shreoshi; Delay, Rona J.; Delay, Eugene R.

2015-01-01

Umami, the fifth basic taste, is elicited by the L-amino acid, glutamate. A unique characteristic of umami taste is the response potentiation by 5’ ribonucleotide monophosphates, which are also capable of eliciting an umami taste. Initial reports using human embryonic kidney (HEK) cells suggested that there is one broadly tuned receptor heterodimer, T1r1+T1r3, which detects L-glutamate and all other L-amino acids. However, there is growing evidence that multiple receptors detect glutamate in the oral cavity. While much is understood about glutamate transduction, the mechanisms for detecting the tastes of other L-amino acids are less well understood. We used calcium imaging of isolated taste sensory cells and taste cell clusters from the circumvallate and foliate papillae of C57BL/6J and T1r3 knockout mice to determine if other receptors might also be involved in detection of L-amino acids. Ratiometric imaging with Fura-2 was used to study calcium responses to monopotassium L-glutamate, L-serine, L-arginine, and L-glutamine, with and without inosine 5’ monophosphate (IMP). The results of these experiments showed that the response patterns elicited by L-amino acids varied significantly across taste sensory cells. L-amino acids other than glutamate also elicited synergistic responses in a subset of taste sensory cells. Along with its role in synergism, IMP alone elicited a response in a large number of taste sensory cells. Our data indicate that synergistic and non-synergistic responses to L-amino acids and IMP are mediated by multiple receptors or possibly a receptor complex. PMID:26110622

Molecular Basis of the Increase in Invertase Activity Elicited by Gravistimulation of Oat-Shoot Pulvini

NASA Technical Reports Server (NTRS)

Wu, Liu-Lai; Song, Il; Kim, Donghern; Kaufman, Peter B.

1993-01-01

An asymmetric (top vs. bottom) increase in invertase activity is elicited by gravistimulation in oatshoot pulvini starting within 3h after treatment. In order to analyze the regulation of invertase gene expression in this system, we examined the effect of gravistimulation on invertase mRNA induction. Total RNA and poly(A)(+)RNA, isolated from oat pulvini, and two oligonucleotide primers, corresponding to two conserved amino-acid sequences (NDPNG and WECPD) found in invertase from other species, were used for the Polymerase Chain Reaction (PCR). A partial-length cDNA (550 base pairs) was obtained and characterized. There was a 52 % deduced amino-acid sequence homology to that of carrot beta-fructosi- dase and a 48 % homology to that of tomato invertase. Northern blot analysis showed that there was an obvious transient accumulation of invertase mRNA elicited by gravistimulation of oat pulvini. The mRNA was rapidly induced to a maximum level at 1h following gravistimulation treatment and gradually decreased afterwards. The mRNA level in the bottom half of the oat pulvinus was significantly higher (five-fold) than that in the top half of the pulvinus tissue. The induction of invertase mRNA was consistent with the transient enhancement of invertase activity during the graviresponse of the pulvinus. These data indicate that the expression of the invertase gene(s) could be regulated by gravistimulation at the transcriptional and/or translational levels. Southern blot analysis showed that there were four genomic DNA fragments hybridized to the invertase cDNA. This suggests that an invertase gene family may exist in oat plants.

A comparative analysis of the avirulence and translational transactivator functions of gene VI of Cauliflower mosaic virus.

PubMed

Palanichelvam, Karuppaiah; Schoelz, James E

2002-02-15

The primary function associated at present with the gene VI product of Cauliflower mosaic virus (CaMV) is that of a translational transactivator (TAV). In this capacity, it alters the host translational machinery to allow reinitiation of translation of other CaMV genes on the polycistronic 35S RNA of CaMV. In addition, the gene VI protein can elicit a specific type of plant defense response called the hypersensitive response (HR) in Nicotiana edwardsonii. In this study, we have adapted the agroinfiltration technique to compare the sequences of CaMV gene VI required for TAV function and elicitation of HR. To measure the activity of the TAV, we coagroinfiltrated gene VI of CaMV strain W260 with a bicistronic GUS reporter plasmid. TAV function could be assayed 4 days postinfiltration, before the onset of HR in N. edwardsonii. Through the use of the TAV and HR assays, we could show that the TAV functions of gene VI of CaMV strains W260 and D4 were equivalent, but only W260 gene VI elicited HR. A mutational analysis of W260 gene VI showed that the structural requirements for elicitation of HR were much more stringent than those for TAV function. Small deletions from either the 5' or 3' end of W260 gene VI abolished its ability to elicit HR, although the TAV function was retained in the mutant. The TAV function could also tolerate a small insertion within gene VI; this insertion abolished the elicitor function. This study provides direct evidence that the TAV function of gene VI is separate from its role as an elicitor of HR.

Fullerene C{sub 60} exposure elicits an oxidative stress response in embryonic zebrafish

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

Usenko, Crystal Y.; Harper, Stacey L.; Tanguay, Robert L.

2008-05-15

Due to its unique physicochemical and optical properties, C{sub 60} has raised interest in commercialization for a variety of products. While several reports have determined this nanomaterial to act as a powerful antioxidant, many other studies have demonstrated a strong oxidative potential through photoactivation. To directly address the oxidative potential of C{sub 60}, the effects of light and chemical supplementation and depletion of glutathione (GSH) on C{sub 60}-induced toxicity were evaluated. Embryonic zebrafish were used as a model organism to examine the potential of C{sub 60} to elicit oxidative stress responses. Reduced light during C{sub 60} exposure significantly decreased mortalitymore » and the incidence of fin malformations and pericardial edema at 200 and 300 ppb C{sub 60}. Embryos co-exposed to the glutathione precursor, N-acetylcysteine (NAC), also showed reduced mortality and pericardial edema; however, fin malformations were not reduced. Conversely, co-exposure to the GSH synthesis inhibitors, buthionine sulfoximine (BSO) and diethyl maleate (DEM), increased the sensitivity of zebrafish to C{sub 60} exposure. Co-exposure of C{sub 60} or its hydroxylated derivative, C{sub 60}(OH){sub 24}, with H{sub 2}O{sub 2} resulted in increased mortality along the concentration gradient of H{sub 2}O{sub 2} for both materials. Microarrays were used to examine the effects of C{sub 60} on the global gene expression at two time points, 36 and 48 h post fertilization (hpf). At both life stages there were alterations in the expression of several key stress response genes including glutathione-S-transferase, glutamate cysteine ligase, ferritin, {alpha}-tocopherol transport protein and heat shock protein 70. These results support the hypothesis that C{sub 60} induces oxidative stress in this model system.« less

Expert elicitation of population-level effects of disturbance

USGS Publications Warehouse

Fleishman, Erica; Burgman, Mark; Runge, Michael C.; Schick, Robert S; Krauss, Scott; Popper, Arthur N.; Hawkins, Anthony

2016-01-01

Expert elicitation is a rigorous method for synthesizing expert knowledge to inform decision making and is reliable and practical when field data are limited. We evaluated the feasibility of applying expert elicitation to estimate population-level effects of disturbance on marine mammals. Diverse experts estimated parameters related to mortality and sublethal injury of North Atlantic right whales (Eubalaena glacialis). We are now eliciting expert knowledge on the movement of right whales among geographic regions to parameterize a spatial model of health. Expert elicitation complements methods such as simulation models or extrapolations from other species, sometimes with greater accuracy and less uncertainty.

HIV-1 Cross-Reactive Primary Virus Neutralizing Antibody Response Elicited by Immunization in Nonhuman Primates

PubMed Central

Wang, Yimeng; O'Dell, Sijy; Turner, Hannah L.; Chiang, Chi-I; Lei, Lin; Guenaga, Javier; Wilson, Richard; Martinez-Murillo, Paola; Doria-Rose, Nicole; Ward, Andrew B.; Mascola, John R.; Wyatt, Richard T.; Karlsson Hedestam, Gunilla B.

2017-01-01

ABSTRACT Elicitation of broadly neutralizing antibody (bNAb) responses is a major goal for the development of an HIV-1 vaccine. Current HIV-1 envelope glycoprotein (Env) vaccine candidates elicit predominantly tier 1 and/or autologous tier 2 virus neutralizing antibody (NAb) responses, as well as weak and/or sporadic cross-reactive tier 2 virus NAb responses with unknown specificity. To delineate the specificity of vaccine-elicited cross-reactive tier 2 virus NAb responses, we performed single memory B cell sorting from the peripheral blood of a rhesus macaque immunized with YU2gp140-F trimers in adjuvant, using JR-FL SOSIP.664, a native Env trimer mimetic, as a sorting probe to isolate monoclonal Abs (MAbs). We found striking genetic and functional convergence of the SOSIP-sorted Ig repertoire, with predominant VH4 or VH5 gene family usage and Env V3 specificity. Of these vaccine-elicited V3-specific MAbs, nearly 20% (6/33) displayed cross-reactive tier 2 virus neutralization, which recapitulated the serum neutralization capacity. Substantial similarities in binding specificity, neutralization breadth and potency, and sequence/structural homology were observed between selected macaque cross-reactive V3 NAbs elicited by vaccination and prototypic V3 NAbs derived from natural infections in humans, highlighting the convergence of this subset of primate V3-specific B cell repertories. Our study demonstrated that cross-reactive primary virus neutralizing B cell lineages could be elicited by vaccination as detected using a standardized panel of tier 2 viruses. Whether these lineages could be expanded to acquire increased breadth and potency of neutralization merits further investigation. IMPORTANCE Elicitation of antibody responses capable of neutralizing diverse HIV-1 primary virus isolates (designated broadly neutralizing antibodies [bNAbs]) remains a high priority for the vaccine field. bNAb responses were so far observed only in response to natural infection within

Gene expression profile and immunological evaluation of unique hypothetical unknown proteins of Mycobacterium leprae by using quantitative real-time PCR.

PubMed

Kim, Hee Jin; Prithiviraj, Kalyani; Groathouse, Nathan; Brennan, Patrick J; Spencer, John S

2013-02-01

The cell-mediated immunity (CMI)-based in vitro gamma interferon release assay (IGRA) of Mycobacterium leprae-specific antigens has potential as a promising diagnostic means to detect those individuals in the early stages of M. leprae infection. Diagnosis of leprosy is a major obstacle toward ultimate disease control and has been compromised in the past by the lack of specific markers. Comparative bioinformatic analysis among mycobacterial genomes identified potential M. leprae-specific proteins called "hypothetical unknowns." Due to massive gene decay and the prevalence of pseudogenes, it is unclear whether any of these proteins are expressed or are immunologically relevant. In this study, we performed cDNA-based quantitative real-time PCR to investigate the expression status of 131 putative open reading frames (ORFs) encoding hypothetical unknowns. Twenty-six of the M. leprae-specific antigen candidates showed significant levels of gene expression compared to that of ESAT-6 (ML0049), which is an important T cell antigen of low abundance in M. leprae. Fifteen of 26 selected antigen candidates were expressed and purified in Escherichia coli. The seroreactivity to these proteins of pooled sera from lepromatous leprosy patients and cavitary tuberculosis patients revealed that 9 of 15 recombinant hypothetical unknowns elicited M. leprae-specific immune responses. These nine proteins may be good diagnostic reagents to improve both the sensitivity and specificity of detection of individuals with asymptomatic leprosy.

Expression profiles of urbilaterian genes uniquely shared between honey bee and vertebrates.

PubMed

Matsui, Toshiaki; Yamamoto, Toshiyuki; Wyder, Stefan; Zdobnov, Evgeny M; Kadowaki, Tatsuhiko

2009-01-12

Large-scale comparison of metazoan genomes has revealed that a significant fraction of genes of the last common ancestor of Bilateria (Urbilateria) is lost in each animal lineage. This event could be one of the underlying mechanisms involved in generating metazoan diversity. However, the present functions of these ancient genes have not been addressed extensively. To understand the functions and evolutionary mechanisms of such ancient Urbilaterian genes, we carried out comprehensive expression profile analysis of genes shared between vertebrates and honey bees but not with the other sequenced ecdysozoan genomes (honey bee-vertebrate specific, HVS genes) as a model. We identified 30 honey bee and 55 mouse HVS genes. Many HVS genes exhibited tissue-selective expression patterns; intriguingly, the expression of 60% of honey bee HVS genes was found to be brain enriched, and 24% of mouse HVS genes were highly expressed in either or both the brain and testis. Moreover, a minimum of 38% of mouse HVS genes demonstrated neuron-enriched expression patterns, and 62% of them exhibited expression in selective brain areas, particularly the forebrain and cerebellum. Furthermore, gene ontology (GO) analysis of HVS genes predicted that 35% of genes are associated with DNA transcription and RNA processing. These results suggest that HVS genes include genes that are biased towards expression in the brain and gonads. They also demonstrate that at least some of Urbilaterian genes retained in the specific animal lineage may be selectively maintained to support the species-specific phenotypes.

Divergent evolution of part of the involucrin gene in the hominoids: Unique intragenic duplications in the gorilla and human

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

Teumer, J.; Green, H.

1989-02-01

The gene for involucrin, an epidermal protein, has been remodeled in the higher primates. Most of the coding region of the human gene consists of a modern segment of repeats derived from a 10-codon sequence present in the ancestral segment of the gene. The modern segment can be divided into early, middle, and late regions. The authors report here the nucleotide sequence of three alleles of the gorilla involucrin gene. Each possesses a modern segment homologous to that of the human and consisting of 10-codon repeats. The early and middle regions are similar to the corresponding regions of the humanmore » allele and are nearly identical among the different gorilla alleles. The late region consists of recent duplications whose pattern is unique in each of the gorilla alleles and in the human allele. The early region is located in what is now the 3{prime} third of the modern segment, and the late, polymorphic region is located in what is now the 5{prime} third. Therefore, as the modern segment expanded during evolution, its 3{prime} end became stabilized, and continuing duplications became confined to its 5{prime} end. The expansion of the involucrin coding region, which began long before the separation of the gorilla and human, has continued in both species after their separation.« less

Expression profiles of urbilaterian genes uniquely shared between honey bee and vertebrates

PubMed Central

Matsui, Toshiaki; Yamamoto, Toshiyuki; Wyder, Stefan; Zdobnov, Evgeny M; Kadowaki, Tatsuhiko

2009-01-01

Background Large-scale comparison of metazoan genomes has revealed that a significant fraction of genes of the last common ancestor of Bilateria (Urbilateria) is lost in each animal lineage. This event could be one of the underlying mechanisms involved in generating metazoan diversity. However, the present functions of these ancient genes have not been addressed extensively. To understand the functions and evolutionary mechanisms of such ancient Urbilaterian genes, we carried out comprehensive expression profile analysis of genes shared between vertebrates and honey bees but not with the other sequenced ecdysozoan genomes (honey bee-vertebrate specific, HVS genes) as a model. Results We identified 30 honey bee and 55 mouse HVS genes. Many HVS genes exhibited tissue-selective expression patterns; intriguingly, the expression of 60% of honey bee HVS genes was found to be brain enriched, and 24% of mouse HVS genes were highly expressed in either or both the brain and testis. Moreover, a minimum of 38% of mouse HVS genes demonstrated neuron-enriched expression patterns, and 62% of them exhibited expression in selective brain areas, particularly the forebrain and cerebellum. Furthermore, gene ontology (GO) analysis of HVS genes predicted that 35% of genes are associated with DNA transcription and RNA processing. Conclusion These results suggest that HVS genes include genes that are biased towards expression in the brain and gonads. They also demonstrate that at least some of Urbilaterian genes retained in the specific animal lineage may be selectively maintained to support the species-specific phenotypes. PMID:19138430

Endophytic actinobacteria: Diversity, secondary metabolism and mechanisms to unsilence biosynthetic gene clusters.

PubMed

Dinesh, Raghavan; Srinivasan, Veeraraghavan; T E, Sheeja; Anandaraj, Muthuswamy; Srambikkal, Hamza

2017-09-01

Endophytic actinobacteria, which reside in the inner tissues of host plants, are gaining serious attention due to their capacity to produce a plethora of secondary metabolites (e.g. antibiotics) possessing a wide variety of biological activity with diverse functions. This review encompasses the recent reports on endophytic actinobacterial species diversity, in planta habitats and mechanisms underlying their mode of entry into plants. Besides, their metabolic potential, novel bioactive compounds they produce and mechanisms to unravel their hidden metabolic repertoire by activation of cryptic or silent biosynthetic gene clusters (BGCs) for eliciting novel secondary metabolite production are discussed. The study also reviews the classical conservative techniques (chemical/biological/physical elicitation, co-culturing) as well as modern microbiology tools (e.g. next generation sequencing) that are being gainfully employed to uncover the vast hidden scaffolds for novel secondary metabolites produced by these endophytes, which would subsequently herald a revolution in drug engineering. The potential role of these endophytes in the agro-environment as promising biological candidates for inhibition of phytopathogens and the way forward to thoroughly exploit this unique microbial community by inducing expression of cryptic BGCs for encoding unseen products with novel therapeutic properties are also discussed.

Dopamine D4 receptor polymorphism modulates cue-elicited heroin craving in Chinese.

PubMed

Shao, Chunhong; Li, Yifeng; Jiang, Kaida; Zhang, Dandan; Xu, Yifeng; Lin, Ling; Wang, Qiuying; Zhao, Min; Jin, Li

2006-06-01

Subjective craving, which contributes to the continuation of drug use in active abuser and the occurrence of relapse in detoxified abusers, is considered to be a central phenomenon in addiction. Dopamine pathway has been implicated in the mechanism underlying the cue-elicited craving for a variety of addictive substances. The objective of this study was to test the hypothesis that heroin addicts carrying D4 dopamine receptor gene (DRD4) variable number tandem repeat (VNTR) long type allele would have higher craving after exposure to a heroin-related cue. Craving was induced by a series of exposure to neutral and heroin-related cue and were assessed in a cohort of Chinese heroin abusers (n=420) recruited from the Voluntary Drug Dependence Treatment Center at Shanghai. Significantly stronger cue-elicited heroin craving was found in individuals carrying DRD4 VNTR long type allele than the non-carriers (F=31.040, p<0.001). As for baseline craving and mean change in craving responding to neutral stimuli, no significance was found (1.06+/-0.34 vs 1.07+/-0.36, F=0.067, p=0.797 and 0.42+/-0.34 vs 0.45+/-0.37, F=0.277, p=0.599, respectively). The results of our study suggest that DRD4 VNTR polymorphism contributes to cue-elicited craving in heroin dependence, indicating DRD4 VNTR represents one of potential genetic risk factors for cue-induced craving.

Intraperitoneal Administration of a Tumor-Associated Antigen SART3, CD40L, and GM-CSF Gene-Loaded Polyplex Micelle Elicits a Vaccine Effect in Mouse Tumor Models

PubMed Central

Furugaki, Kouichi; Cui, Lin; Kunisawa, Yumi; Osada, Kensuke; Shinkai, Kentaro; Tanaka, Masao; Kataoka, Kazunori; Nakano, Kenji

2014-01-01

Polyplex micelles have demonstrated biocompatibility and achieve efficient gene transfection in vivo. Here, we investigated a polyplex micelle encapsulating genes encoding the tumor-associated antigen squamous cell carcinoma antigen recognized by T cells-3 (SART3), adjuvant CD40L, and granulocyte macrophage colony-stimulating factor (GM-CSF) as a DNA vaccine platform in mouse tumor models with different types of major histocompatibility antigen complex (MHC). Intraperitoneally administrated polyplex micelles were predominantly found in the lymph nodes, spleen, and liver. Compared with mock controls, the triple gene vaccine significantly prolonged the survival of mice harboring peritoneal dissemination of CT26 colorectal cancer cells, of which long-term surviving mice showed complete rejection when re-challenged with CT26 tumors. Moreover, the DNA vaccine inhibited the growth and metastasis of subcutaneous CT26 and Lewis lung tumors in BALB/c and C57BL/6 mice, respectively, which represent different MHC haplotypes. The DNA vaccine highly stimulated both cytotoxic T lymphocyte and natural killer cell activities, and increased the infiltration of CD11c+ DCs and CD4+/CD8a+ T cells into tumors. Depletion of CD4+ or CD8a+ T cells by neutralizing antibodies deteriorated the anti-tumor efficacy of the DNA vaccine. In conclusion, a SART3/CD40L+GM-CSF gene-loaded polyplex micelle can be applied as a novel vaccine platform to elicit tumor rejection immunity regardless of the recipient MHC haplotype. PMID:25013909

Molecular Mechanisms Elicited by d-Aspartate in Leydig Cells and Spermatogonia

PubMed Central

Di Fiore, Maria Maddalena; Santillo, Alessandra; Falvo, Sara; Longobardi, Salvatore; Chieffi Baccari, Gabriella

2016-01-01

A bulk of evidence suggests that d-aspartate (d-Asp) regulates steroidogenesis and spermatogenesis in vertebrate testes. This review article focuses on intracellular signaling mechanisms elicited by d-Asp possibly via binding to the N-methyl-d-aspartate receptor (NMDAR) in both Leydig cells, and spermatogonia. In Leydig cells, the amino acid upregulates androgen production by eliciting the adenylate cyclase-cAMP and/or mitogen-activated protein kinase (MAPK) pathways. d-Asp treatment enhances gene and protein expression of enzymes involved in the steroidogenic cascade. d-Asp also directly affects spermatogonial mitotic activity. In spermatogonial GC-1 cells, d-Asp induces phosphorylation of MAPK and AKT serine-threonine kinase proteins, and stimulates expression of proliferating cell nuclear antigen (PCNA) and aurora kinase B (AURKB). Further stimulation of spermatogonial GC-1 cell proliferation might come from estradiol/estrogen receptor β (ESR2) interaction. d-Asp modulates androgen and estrogen levels as well as the expression of their receptors in the rat epididymis by acting on mRNA levels of Srd5a1 and Cyp19a1 enzymes, hence suggesting involvement in spermatozoa maturation. PMID:27428949

o-p′-DDT-mediated uterotrophy and gene expression in immature C57BL/6 mice and Sprague–Dawley rats

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

Kwekel, Joshua C.; Forgacs, Agnes L.; Center for Integrative Toxicology, Michigan State University, East Lansing, MI

1,1,1-Trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane (o,p′-DDT) is an organochlorine pesticide and endocrine disruptor known to activate the estrogen receptor. Comprehensive ligand- and species-comparative dose- and time-dependent studies were conducted to systematically assess the uterine physiological, morphological and gene expression responses elicited by o,p′-DDT and ethynyl estradiol (EE) in immature ovariectomized C57BL/6 mice and Sprague–Dawley rats. Custom cDNA microarrays were used to identify conserved and divergent differential gene expression responses. A total of 1256 genes were differentially expressed by both ligands in both species, 559 of which exhibited similar temporal expression profiles suggesting that o,p′-DDT elicits estrogenic effects at high doses when compared to EE.more » However, 51 genes exhibited species-specific uterine expression elicited by o,p′-DDT. For example, carbonic anhydrase 2 exhibited species- and ligand-divergent expression as confirmed by quantitative real-time PCR. The identification of comparable temporal phenotypic responses linked to gene expression demonstrates that systematic comparative gene expression assessments are valuable for elucidating conserved and divergent estrogen signaling mechanisms in rodent uterotrophy. - Highlights: • o,p′-DDT and enthynyl estradiol (EE) both elicit uterotrophy in mice and rats. • o,p′-DDT and EE have different kinetics in uterine wet weight induction. • o,p′-DDT elicited stromal hypertrophy in rats but myometrial hypertrophy in mice. • 1256 genes were differentially expressed by both ligands in both species. • Only 51 genes had species-specific uterine expression.« less

Cannabis cue-elicited craving and the reward neurocircuitry.

PubMed

Filbey, Francesca M; DeWitt, Samuel J

2012-07-02

Cue-elicited craving or the intense desire to consume a substance following exposure to a conditioned drug cue is one of the primary behavioral symptoms of substance use disorders (SUDs). While the concept of cue-elicited craving is well characterized in alcohol and other substances of abuse, only recently has it been described in cannabis. A review of the extant literature has established that cue-elicited craving is a powerful reinforcer that contributes to drug-seeking for cannabis. Further, emergent research has begun to identify the neurobiological systems and neural mechanisms associated with this behavior. What research shows is that while theories of THC's effects on the dopaminergic-reward system remain divergent, cannabis cues elicit neural activation in the brain's reward network. Copyright © 2011 Elsevier Inc. All rights reserved.

Gender differences in autobiographical memory for everyday events: retrieval elicited by SenseCam images versus verbal cues.

PubMed

St Jacques, Peggy L; Conway, Martin A; Cabeza, Roberto

2011-10-01

Gender differences are frequently observed in autobiographical memory (AM). However, few studies have investigated the neural basis of potential gender differences in AM. In the present functional MRI (fMRI) study we investigated gender differences in AMs elicited using dynamic visual images vs verbal cues. We used a novel technology called a SenseCam, a wearable device that automatically takes thousands of photographs. SenseCam differs considerably from other prospective methods of generating retrieval cues because it does not disrupt the ongoing experience. This allowed us to control for potential gender differences in emotional processing and elaborative rehearsal, while manipulating how the AMs were elicited. We predicted that males would retrieve more richly experienced AMs elicited by the SenseCam images vs the verbal cues, whereas females would show equal sensitivity to both cues. The behavioural results indicated that there were no gender differences in subjective ratings of reliving, importance, vividness, emotion, and uniqueness, suggesting that gender differences in brain activity were not due to differences in these measures of phenomenological experience. Consistent with our predictions, the fMRI results revealed that males showed a greater difference in functional activity associated with the rich experience of SenseCam vs verbal cues, than did females.

Gene Expression Profile and Immunological Evaluation of Unique Hypothetical Unknown Proteins of Mycobacterium leprae by Using Quantitative Real-Time PCR

PubMed Central

Prithiviraj, Kalyani; Groathouse, Nathan; Brennan, Patrick J.; Spencer, John S.

2013-01-01

The cell-mediated immunity (CMI)-based in vitro gamma interferon release assay (IGRA) of Mycobacterium leprae-specific antigens has potential as a promising diagnostic means to detect those individuals in the early stages of M. leprae infection. Diagnosis of leprosy is a major obstacle toward ultimate disease control and has been compromised in the past by the lack of specific markers. Comparative bioinformatic analysis among mycobacterial genomes identified potential M. leprae-specific proteins called “hypothetical unknowns.” Due to massive gene decay and the prevalence of pseudogenes, it is unclear whether any of these proteins are expressed or are immunologically relevant. In this study, we performed cDNA-based quantitative real-time PCR to investigate the expression status of 131 putative open reading frames (ORFs) encoding hypothetical unknowns. Twenty-six of the M. leprae-specific antigen candidates showed significant levels of gene expression compared to that of ESAT-6 (ML0049), which is an important T cell antigen of low abundance in M. leprae. Fifteen of 26 selected antigen candidates were expressed and purified in Escherichia coli. The seroreactivity to these proteins of pooled sera from lepromatous leprosy patients and cavitary tuberculosis patients revealed that 9 of 15 recombinant hypothetical unknowns elicited M. leprae-specific immune responses. These nine proteins may be good diagnostic reagents to improve both the sensitivity and specificity of detection of individuals with asymptomatic leprosy. PMID:23239802

The role of macrophage mediators in respirable quartz-elicited inflammation

NASA Astrophysics Data System (ADS)

van Berlo, D.; Albrecht, C.; Knaapen, A. M.; van Schooten, F. J.; Schins, R. P. F.

2009-02-01

The instigation and persistence of an inflammatory response is widely considered to be critically important in quartz-induced lung cancer and fibrosis. Macrophages have been long recognised as a crucial player in pulmonary inflammation, but evidence for the role of type II epithelial cells is accumulating. Investigations were performed in the rat lung type II cell line RLE and the rat alveolar macrophage cell line NR8383 using Western blotting, NF-κB immunohistochemistry and qRT-PCR of the pro-inflammatory genes iNOS and COX-2, as well as the cellular stress gene HO-1. The direct effect of quartz on pro-inflammatory signalling cascades and gene expression in RLE cells was compared to the effect of conditioned media derived from quartz-treated NR8383 cells. Conditioned media activated the NF-κB signalling pathway and induced a far stronger upregulation of iNOS mRNA than quartz itself. Quartz elicited a stronger, progressive induction of COX-2 and HO-1 mRNA. Our results suggest a differentially mediated inflammatory response, in which reactive particles themselves induce oxidative stress and activation of COX-2, while mediators released from particle-activated macrophages trigger NF-κB activation and iNOS expression in type II cells.

Unique mutation portraits and frequent COL2A1 gene alteration in chondrosarcoma

PubMed Central

Totoki, Yasushi; Yoshida, Akihiko; Hosoda, Fumie; Nakamura, Hiromi; Hama, Natsuko; Ogura, Koichi; Yoshida, Aki; Fujiwara, Tomohiro; Arai, Yasuhito; Toguchida, Junya; Tsuda, Hitoshi; Miyano, Satoru; Kawai, Akira

2014-01-01

Chondrosarcoma is the second most frequent malignant bone tumor. However, the etiological background of chondrosarcomagenesis remains largely unknown, along with details on molecular alterations and potential therapeutic targets. Massively parallel paired-end sequencing of whole genomes of 10 primary chondrosarcomas revealed that the process of accumulation of somatic mutations is homogeneous irrespective of the pathological subtype or the presence of IDH1 mutations, is unique among a range of cancer types, and shares significant commonalities with that of prostate cancer. Clusters of structural alterations localized within a single chromosome were observed in four cases. Combined with targeted resequencing of additional cartilaginous tumor cohorts, we identified somatic alterations of the COL2A1 gene, which encodes an essential extracellular matrix protein in chondroskeletal development, in 19.3% of chondrosarcoma and 31.7% of enchondroma cases. Epigenetic regulators (IDH1 and YEATS2) and an activin/BMP signal component (ACVR2A) were recurrently altered. Furthermore, a novel FN1-ACVR2A fusion transcript was observed in both chondrosarcoma and osteochondromatosis cases. With the characteristic accumulative process of somatic changes as a background, molecular defects in chondrogenesis and aberrant epigenetic control are primarily causative of both benign and malignant cartilaginous tumors. PMID:25024164

Application and Evaluation of an Expert Judgment Elicitation Procedure for Correlations.

PubMed

Zondervan-Zwijnenburg, Mariëlle; van de Schoot-Hubeek, Wenneke; Lek, Kimberley; Hoijtink, Herbert; van de Schoot, Rens

2017-01-01

The purpose of the current study was to apply and evaluate a procedure to elicit expert judgments about correlations, and to update this information with empirical data. The result is a face-to-face group elicitation procedure with as its central element a trial roulette question that elicits experts' judgments expressed as distributions. During the elicitation procedure, a concordance probability question was used to provide feedback to the experts on their judgments. We evaluated the elicitation procedure in terms of validity and reliability by means of an application with a small sample of experts. Validity means that the elicited distributions accurately represent the experts' judgments. Reliability concerns the consistency of the elicited judgments over time. Four behavioral scientists provided their judgments with respect to the correlation between cognitive potential and academic performance for two separate populations enrolled at a specific school in the Netherlands that provides special education to youth with severe behavioral problems: youth with autism spectrum disorder (ASD), and youth with diagnoses other than ASD. Measures of face-validity, feasibility, convergent validity, coherence, and intra-rater reliability showed promising results. Furthermore, the current study illustrates the use of the elicitation procedure and elicited distributions in a social science application. The elicited distributions were used as a prior for the correlation, and updated with data for both populations collected at the school of interest. The current study shows that the newly developed elicitation procedure combining the trial roulette method with the elicitation of correlations is a promising tool, and that the results of the procedure are useful as prior information in a Bayesian analysis.

EXPLICIT: a feasibility study of remote expert elicitation in health technology assessment.

PubMed

Grigore, Bogdan; Peters, Jaime; Hyde, Christopher; Stein, Ken

2017-09-04

Expert opinion is often sought to complement available information needed to inform model-based economic evaluations in health technology assessments. In this context, we define expert elicitation as the process of encoding expert opinion on a quantity of interest, together with associated uncertainty, as a probability distribution. When availability for face-to-face expert elicitation with a facilitator is limited, elicitation can be conducted remotely, overcoming challenges of finding an appropriate time to meet the expert and allowing access to experts situated too far away for practical face-to-face sessions. However, distance elicitation is associated with reduced response rates and limited assistance for the expert during the elicitation session. The aim of this study was to inform the development of a remote elicitation tool by exploring the influence of mode of elicitation on elicited beliefs. An Excel-based tool (EXPLICIT) was developed to assist the elicitation session, including the preparation of the expert and recording of their responses. General practitioners (GPs) were invited to provide expert opinion about population alcohol consumption behaviours. They were randomised to complete the elicitation by either a face-to-face meeting or email. EXPLICIT was used in the elicitation sessions for both arms. Fifteen GPs completed the elicitation session. Those conducted by email were longer than the face-to-face sessions (13 min 30 s vs 10 min 26 s, p = 0.1) and the email-elicited estimates contained less uncertainty. However, the resulting aggregated distributions were comparable. EXPLICIT was useful in both facilitating the elicitation task and in obtaining expert opinion from experts via email. The findings support the opinion that remote, self-administered elicitation is a viable approach within the constraints of HTA to inform policy making, although poor response rates may be observed and additional time for individual sessions may be required.

Brain gene expression changes elicited by peripheral vitellogenin knockdown in the honey bee.

PubMed

Wheeler, M M; Ament, S A; Rodriguez-Zas, S L; Robinson, G E

2013-10-01

Vitellogenin (Vg) is best known as a yolk protein precursor. Vg also functions to regulate behavioural maturation in adult honey bee workers, but the underlying molecular mechanisms by which it exerts this novel effect are largely unknown. We used abdominal vitellogenin (vg) knockdown with RNA interference (RNAi) and brain transcriptomic profiling to gain insights into how Vg influences honey bee behavioural maturation. We found that vg knockdown caused extensive gene expression changes in the bee brain, with much of this transcriptional response involving changes in central biological functions such as energy metabolism. vg knockdown targeted many of the same genes that show natural, maturation-related differences, but the direction of change for the genes in these two contrasts was not correlated. By contrast, vg knockdown targeted many of the same genes that are regulated by juvenile hormone (JH) and there was a significant correlation for the direction of change for the genes in these two contrasts. These results indicate that the tight coregulatory relationship that exists between JH and Vg in the regulation of honey bee behavioural maturation is manifest at the genomic level and suggest that these two physiological factors act through common pathways to regulate brain gene expression and behaviour. © 2013 Royal Entomological Society.

Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery

PubMed Central

Best, Simon R.; Peng, Shiwen; Juang, Chi-Mou; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.; Pai, Sara I.

2009-01-01

DNA vaccines are an attractive approach to eliciting antigen-specific immunity. Intracellular targeting of tumor antigens through its linkage to immunostimulatory molecules such as calreticulin (CRT) can improve antigen processing and presentation through the MHC Class I pathway and increase cytotoxic CD8+ T cell production. However, even with these enhancements, the efficacy of such immunotherapeutic strategies is dependent on the identification of an effective route and method of DNA administration. Electroporation and gene gun-mediated particle delivery are leading methods of DNA vaccine delivery that can generate protective and therapeutic levels of immune responses in experimental models. In this study, we perform a head-to-head comparison of three methods of vaccination – conventional intramuscular injection, electroporation mediated intramuscular delivery, and epidermal gene gun-mediated particle delivery - in the ability to generate antigen specific cytotoxic CD8+ T cell responses as well as anti-tumor immune responses against an HPV-16 E7 expressing tumor cell line using the pNGVL4a-CRT/E7(detox) DNA vaccine. Vaccination via electroporation generated the highest number of E7-specific cytotoxic CD8+ T cells, which correlated to improved outcomes in the treatment of growing tumors. In addition, we demonstrate that electroporation results in significantly higher levels of circulating protein compared to gene gun or intramuscular vaccination, which likely enhances calreticulin’s role as a local tumor anti-angiogenesis agent. We conclude that electroporation is a promising method for delivery of HPV DNA vaccines and should be considered for DNA vaccine delivery in human clinical trials. PMID:19622402

Host and non-host pathogens elicit different jasmonate/ethylene responses in Arabidopsis.

PubMed

Zimmerli, Laurent; Stein, Mónica; Lipka, Volker; Schulze-Lefert, Paul; Somerville, Shauna

2004-12-01

Arabidopsis does not support the growth and asexual reproduction of the barley pathogen, Blumeria graminis f. sp. hordei Bgh). A majority of germlings fail to penetrate the epidermal cell wall and papillae. To gain additional insight into this interaction, we determined whether the salicylic acid (SA) or jasmonate (JA)/ethylene (ET) defence pathways played a role in blocking barley powdery mildew infections. Only the eds1 mutant and NahG transgenics supported a modest increase in penetration success by the barley powdery mildew. We also compared the global gene expression patterns of Arabidopsis inoculated with the non-host barley powdery mildew to those inoculated with a virulent, host powdery mildew, Erysiphe cichoracearum. Genes repressed by inoculations with non-host and host powdery mildews relative to non-inoculated control plants accounted for two-thirds of the differentially expressed genes. A majority of these genes encoded components of photosynthesis and general metabolism. Consistent with this observation, Arabidopsis growth was inhibited following inoculation with Bgh, suggesting a shift in resource allocation from growth to defence. A number of defence-associated genes were induced during both interactions. These genes likely are components of basal defence responses, which do not effectively block host powdery mildew infections. In addition, genes encoding defensins, anti-microbial peptides whose expression is under the control of the JA/ET signalling pathway, were induced exclusively by non-host pathogens. Ectopic activation of JA/ET signalling protected Arabidopsis against two biotrophic host pathogens. Taken together, these data suggest that biotrophic host pathogens must either suppress or fail to elicit the JA/ET signal transduction pathway.

Developing Socio-Cultural Scaffolding Model to Elicit Learners's Speech Production

ERIC Educational Resources Information Center

Englishtina, Inti

2015-01-01

This study is concerned with developing scaffolding model to elicit bilingual kindergarten children's English speech production. It is aimed at describing what the teachers need in eliciting their students' speech production; how a scaffolding model should be developed to elicit the children's speech production; and how effective is the…

Eliciting Spontaneous Speech in Bilingual Students: Methods & Techniques.

ERIC Educational Resources Information Center

Cornejo, Ricardo J.; And Others

Intended to provide practical information pertaining to methods and techniques for speech elicitation and production, the monograph offers specific methods and techniques to elicit spontaneous speech in bilingual students. Chapter 1, "Traditional Methodologies for Language Production and Recording," presents an overview of studies using…

A potential disruptive technology in vaccine development: gene-based vaccines and their application to infectious diseases.

PubMed

Kaslow, David C

2004-10-01

Vaccine development requires an amalgamation of disparate disciplines and has unique economic and regulatory drivers. Non-viral gene-based delivery systems, such as formulated plasmid DNA, are new and potentially disruptive technologies capable of providing 'cheaper, simpler, and more convenient-to-use' vaccines. Typically and somewhat ironically, disruptive technologies have poorer product performance, at least in the near-term, compared with the existing conventional technologies. Because successful product development requires that the product's performance must meet or exceed the efficacy threshold for a desired application, the appropriate selection of the initial product applications for a disruptive technology is critical for its successful evolution. In this regard, the near-term successes of gene-based vaccines will likely be for protection against bacterial toxins and acute viral and bacterial infections. Recent breakthroughs, however, herald increasing rather than languishing performance improvements in the efficacy of gene-based vaccines. Whether gene-based vaccines ultimately succeed in eliciting protective immunity in humans to persistent intracellular pathogens, such as HIV, malaria and tuberculosis, for which the conventional vaccine technologies have failed, remains to be determined. A success against any one of the persistent intracellular pathogens would be sufficient proof that gene-based vaccines represent a disruptive technology against which future vaccine technologies will be measured.

Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERBα/β activation in aryl hydrocarbon receptor-elicited hepatotoxicity

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

Fader, Kelly A.; Nault, Rance

Persistent aryl hydrocarbon receptor (AhR) agonists elicit dose-dependent hepatic lipid accumulation, oxidative stress, inflammation, and fibrosis in mice. Iron (Fe) promotes AhR-mediated oxidative stress by catalyzing reactive oxygen species (ROS) production. To further characterize the role of Fe in AhR-mediated hepatotoxicity, male C57BL/6 mice were orally gavaged with sesame oil vehicle or 0.01–30 μg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) every 4 days for 28 days. Duodenal epithelial and hepatic RNA-Seq data were integrated with hepatic AhR ChIP-Seq, capillary electrophoresis protein measurements, and clinical chemistry analyses. TCDD dose-dependently repressed hepatic expression of hepcidin (Hamp and Hamp2), the master regulator of systemic Fe homeostasis, resultingmore » in a 2.6-fold increase in serum Fe with accumulating Fe spilling into urine. Total hepatic Fe levels were negligibly increased while transferrin saturation remained unchanged. Furthermore, TCDD elicited dose-dependent gene expression changes in heme biosynthesis including the induction of aminolevulinic acid synthase 1 (Alas1) and repression of uroporphyrinogen decarboxylase (Urod), leading to a 50% increase in hepatic hemin and a 13.2-fold increase in total urinary porphyrins. Consistent with this heme accumulation, differential gene expression suggests that heme activated BACH1 and REV-ERBα/β, causing induction of heme oxygenase 1 (Hmox1) and repression of fatty acid biosynthesis, respectively. Collectively, these results suggest that Hamp repression, Fe accumulation, and increased heme levels converge to promote oxidative stress and the progression of TCDD-elicited hepatotoxicity. - Highlights: • TCDD represses hepatic hepcidin expression, leading to systemic iron overloading. • Dysregulation of heme biosynthesis is consistent with heme and porphyrin accumulation. • Heme-activated REV-ERBα/β repress circadian-regulated hepatic lipid metabolism. • Disruption of iron

Biosynthetic Potential of Phylogenetically Unique Endophytic Actinomycetes from Tropical Plants▿ †

PubMed Central

Janso, Jeffrey E.; Carter, Guy T.

2010-01-01

The culturable diversity of endophytic actinomycetes associated with tropical, native plants is essentially unexplored. In this study, 123 endophytic actinomycetes were isolated from tropical plants collected from several locations in Papua New Guinea and Mborokua Island, Solomon Islands. Isolates were found to be prevalent in roots but uncommon in leaves. Initially, isolates were dereplicated to the strain level by ribotyping. Subsequent characterization of 105 unique strains by 16S rRNA gene sequence analysis revealed that 17 different genera were represented, and rare genera, such as Sphaerisporangium and Planotetraspora, which have never been previously reported to be endophytic, were quite prevalent. Phylogenetic analyses grouped many of the strains into clades distinct from known genera within Thermomonosporaceae and Micromonosporaceae, indicating that they may be unique genera. Bioactivity testing and liquid chromatography-mass spectrometry (LC-MS) profiling of crude fermentation extracts were performed on 91 strains. About 60% of the extracts exhibited bioactivity or displayed LC-MS profiles with spectra indicative of secondary metabolites. The biosynthetic potential of 29 nonproductive strains was further investigated by the detection of putative polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) genes. Despite their lack of detectable secondary metabolite production in fermentation, most were positive for type I (66%) and type II (79%) PKS genes, and all were positive for NRPS genes. These results suggest that tropical plants from New Guinea and the adjacent archipelago are hosts to unique endophytic actinomycetes that possess significant biosynthetic potential. PMID:20472734

Look Who Is Talking Now: Eliciting the Concept of Fatherhood Among Filipino Fathers Using Metaphor Analysis.

PubMed

Villamor, Neil Jupiter E; de Guzman, Allan B; Matienzo, Evangeline T

2016-12-29

Although the increased interest in investigating the dynamics of fatherhood in developed nations has been documented in the literature, its collective meaning and implications in nursing remain largely unknown in the context of East Asia, especially in developing countries such as the Philippines. Capitalizing on the unique power of metaphors to improve the understanding of complex and abstract ideas and to shape healthcare practices, this qualitative semiotic investigation intended to define the essence of fatherhood from the perspective of Filipino fathers. This study focused on a group of 28 first-time and 22 second-time fathers who were recruited from the largest maternal and newborn tertiary government hospital in the Philippines. To capture the richness and thickness of fatherhood as a subjective human reality, doodling and elicitation interviews were employed to promote data triangulation. Furthermore, semiosis was used as the data analytic framework to better understand the ontology and epistemology of the elicited metaphors. In addition, a member-checking procedure was employed to validate the themes that emerged from the inductive approach. This study provides a conceptualization of "The House of Fatherhood," which illustrates the uniqueness of the experience of fatherhood as identity defining, maturity enabling, and duality affirming. The pillars of fatherhood that were identified in this article provide a valuable framework for Filipino healthcare providers and program administrators in the field of maternal and child nursing to identify scaffolding measures and other support mechanisms to address the needs and concerns of Filipino fathers and their journey to fatherhood in a more effective and holistic way.

Freeze or Flee? Negative Stimuli Elicit Selective Responding

ERIC Educational Resources Information Center

Estes, Zachary; Verges, Michelle

2008-01-01

Humans preferentially attend to negative stimuli. A consequence of this automatic vigilance for negative valence is that negative words elicit slower responses than neutral or positive words on a host of cognitive tasks. Some researchers have speculated that negative stimuli elicit a general suppression of motor activity, akin to the freezing…

Small-molecule elicitation of microbial secondary metabolites.

PubMed

Pettit, Robin K

2011-07-01

Microbial natural products continue to be an unparalleled resource for pharmaceutical lead discovery, but the rediscovery rate is high. Bacterial and fungal sequencing studies indicate that the biosynthetic potential of many strains is much greater than that observed by fermentation. Prodding the expression of such silent (cryptic) pathways will allow us to maximize the chemical diversity available from microorganisms. Cryptic metabolic pathways can be accessed in the laboratory using molecular or cultivation-based approaches. A targeted approach related to cultivation-based methods is the application of small-molecule elicitors to specifically affect transcription of secondary metabolite gene clusters. With the isolation of the novel secondary metabolites lunalides A and B, oxylipins, cladochromes F and G, nygerone A, chaetoglobosin-542, -540 and -510, sphaerolone, dihydrosphaerolone, mutolide and pestalone, and the enhanced production of known secondary metabolites like penicillin and bacitracin, chemical elicitation is proving to be an effective way to augment natural product libraries. © 2010 The Authors. Journal compilation © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

Elicitation of gymnemic acid production in cell suspension cultures of Gymnema sylvestre R.Br. through endophytic fungi.

PubMed

Netala, Vasudeva Reddy; Kotakadi, Venkata Subbaiah; Gaddam, Susmila Aparna; Ghosh, Sukhendu Bikash; Tartte, Vijaya

2016-12-01

The enhancement of plant secondary metabolite production in cell suspension cultures through biotic or abiotic elicitation has become a potential biotechnological approach for commercialization or large-scale production of bioactive compounds. Gymnema sylvestre R.Br. is an important medicinal plant, rich in a group of oleanane triterpenoid saponins called gymnemic acid, well known for its anti-diabetic activity. Two endophytic fungal strains were isolated from the leaves of G. sylvestre and identified as Polyancora globosa and Xylaria sp. based on the PCR amplification and internal transcribed spacer (ITS 1-5.8S-ITS 2) sequencing of 18S rRNA gene. The process of elicitation of cell suspension cultures of G. sylvestre with dried powder of fungal mycelia (DPFM) and extracellular culture filtrate (ECF) of endophytic fungi consistently enhanced the accumulation of gymnemic acid and the DPFM was proved to be an effective elicitor when compared to the ECF. The DPFM elicited the gymnemic acid content in the range of 2.57-10.45-fold, while the ECF elicited the gymnemic acid content in the range of 2.39-7.8-fold. P. globosa, a novel and a rare endophytic fungal strain, has shown a great influence on the production of gymnemic acid. Cell suspension cultures elicited with DPFM of P. globosa produced higher amount of gymnemic acid content (124.23 mg/g dried cell weight) compared to the cultures elicited with DPFM of Xylaria sp. (102.24 mg/g DCW). But the cultures treated with consortium of DPFM of both fungi showed great influence on the production of gymnemic acid (139.98 mg/g DCW) than the cultures treated with DPFM alone. Similarly, cultures treated with consortium of ECF of both fungi produced more gymnemic acid content (94.86 mg/g DCW) compared with cultures treated with ECF of Xylaria sp. (77.93 mg/g DCW) and ECF of P. globosa (78.65 mg/g DCW) alone.

Eliciting expert opinion for economic models: an applied example.

PubMed

Leal, José; Wordsworth, Sarah; Legood, Rosa; Blair, Edward

2007-01-01

Expert opinion is considered as a legitimate source of information for decision-analytic modeling where required data are unavailable. Our objective was to develop a practical computer-based tool for eliciting expert opinion about the shape of the uncertainty distribution around individual model parameters. We first developed a prepilot survey with departmental colleagues to test a number of alternative approaches to eliciting opinions on the shape of the uncertainty distribution around individual parameters. This information was used to develop a survey instrument for an applied clinical example. This involved eliciting opinions from experts to inform a number of parameters involving Bernoulli processes in an economic model evaluating DNA testing for families with a genetic disease, hypertrophic cardiomyopathy. The experts were cardiologists, clinical geneticists, and laboratory scientists working with cardiomyopathy patient populations and DNA testing. Our initial prepilot work suggested that the more complex elicitation techniques advocated in the literature were difficult to use in practice. In contrast, our approach achieved a reasonable response rate (50%), provided logical answers, and was generally rated as easy to use by respondents. The computer software user interface permitted graphical feedback throughout the elicitation process. The distributions obtained were incorporated into the model, enabling the use of probabilistic sensitivity analysis. There is clearly a gap in the literature between theoretical elicitation techniques and tools that can be used in applied decision-analytic models. The results of this methodological study are potentially valuable for other decision analysts deriving expert opinion.

Unique allosteric regulation of 5-hydroxytryptamine receptor-mediated signal transduction by oleamide

PubMed Central

Thomas, Elizabeth A.; Carson, Monica J.; Neal, Michael J.; Sutcliffe, J. Gregor

1997-01-01

The effects of oleamide, an amidated lipid isolated from the cerebrospinal fluid of sleep-deprived cats, on serotonin receptor-mediated responses were investigated in cultured mammalian cells. In rat P11 cells, which endogenously express the 5-hydroxytryptamine2A (5HT2A) receptor, oleamide significantly potentiated 5HT-induced phosphoinositide hydrolysis. In HeLa cells expressing the 5HT7 receptor subtype, oleamide caused a concentration-dependent increase in cAMP accumulation but with lower efficacy than that observed by 5HT. This effect was not observed in untransfected HeLa cells. Clozapine did not prevent the increase in cAMP elicited by oleamide, and ketanserin caused an ≈65% decrease. In the presence of 5HT, oleamide had the opposite effect on cAMP, causing insurmountable antagonism of the concentration-effect curve to 5HT, but had no effect on cAMP levels elicited by isoproterenol or forskolin. These results indicate that oleamide can modulate 5HT-mediated signal transduction at different subtypes of mammalian 5HT receptors. Additionally, our data indicate that oleamide acts at an apparent allosteric site on the 5HT7 receptor and elicits functional responses via activation of this site. This represents a unique mechanism of activation for 5HT G protein-coupled receptors and suggests that G protein-coupled neurotransmitter receptors may act like their iontropic counterparts (i.e., γ-aminobutyric acid type A receptors) in that there may be several binding sites on the receptor that regulate functional activity with varying efficacies. PMID:9391162

Time course of brain activation elicited by basic emotions.

PubMed

Hot, Pascal; Sequeira, Henrique

2013-11-13

Whereas facial emotion recognition protocols have shown that each discrete emotion has a specific time course of brain activation, there is no electrophysiological evidence to support these findings for emotional induction by complex pictures. Our objective was to specify the differences between the time courses of brain activation elicited by feelings of happiness and, with unpleasant pictures, by feelings of disgust and sadness. We compared event-related potentials (ERPs) elicited by the watching of high-arousing pictures from the International Affective Picture System, selected to induce specific emotions. In addition to a classical arousal effect on late positive components, we found specific ERP patterns for each emotion in early temporal windows (<200 ms). Disgust was the first emotion to be associated with different brain processing after 140 ms, whereas happiness and sadness differed in ERPs elicited at the frontal and central sites after 160 ms. Our findings highlight the limits of the classical averaging of ERPs elicited by different emotions inside the same valence and suggest that each emotion could elicit a specific temporal pattern of brain activation, similar to those observed with emotional face recognition.

Unique gene alterations are induced in FACS-purified Fos-positive neurons activated during cue-induced relapse to heroin seeking.

PubMed

Fanous, Sanya; Guez-Barber, Danielle H; Goldart, Evan M; Schrama, Regina; Theberge, Florence R M; Shaham, Yavin; Hope, Bruce T

2013-01-01

Cue-induced heroin seeking after prolonged withdrawal is associated with neuronal activation and altered gene expression in prefrontal cortex (PFC). However, these previous studies assessed gene expression in all neurons regardless of their activity state during heroin seeking. Using Fos as a marker of neural activity, we describe distinct molecular alterations induced in activated versus non-activated neurons during cue-induced heroin seeking after prolonged withdrawal. We trained rats to self-administer heroin for 10 days (6 h/day) and assessed cue-induced heroin seeking in extinction tests after 14 or 30 days. We used fluorescent-activated cell sorting (FACS) to purify Fos-positive and Fos-negative neurons from PFC 90 min after extinction testing. Flow cytometry showed that Fos-immunoreactivity was increased in less than 10% of sparsely distributed PFC neurons. mRNA levels of the immediate early genes fosB, arc, egr1, and egr2, as well as npy and map2k6, were increased in Fos-positive, but not Fos-negative, neurons. In support of these findings, double-label immunohistochemistry indicated substantial coexpression of neuropeptide Y (NPY)- and Arc-immunoreactivity in Fos-positive neurons. Our data indicate that cue-induced relapse to heroin seeking after prolonged withdrawal induces unique molecular alterations within activated PFC neurons that are distinct from those observed in the surrounding majority of non-activated neurons. Published 2012. This article is a US Government work and is in the public domain in the USA.

Remodeling of ribosomal genes in somatic cells by Xenopus egg extract

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

Ostrup, Olga, E-mail: osvarcova@gmail.com; Stem Cell Epigenetics Laboratory, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo; Norwegian Center for Stem Cell Research, Oslo

Highlights: {yields} Xenopus egg extract remodels nuclei and alter cell growth characteristics. {yields} Ribosomal genes are reprogrammed within 6 h after extract exposure. {yields} rDNA reprogramming involves promoter targeting of SNF2H remodeling complex. {yields} Xenopus egg extract does not initiate stress-related response in somatic cells. {yields} Aza-cytidine elicits a stress-induced response in reprogrammed cells. -- Abstract: Extracts from Xenopus eggs can reprogram gene expression in somatic nuclei, however little is known about the earliest processes associated with the switch in the transcriptional program. We show here that an early reprogramming event is the remodeling of ribosomal chromatin and gene expression.more » This occurs within hours of extract treatment and is distinct from a stress response. Egg extract elicits remodeling of the nuclear envelope, chromatin and nucleolus. Nucleolar remodeling involves a rapid and stable decrease in ribosomal gene transcription, and promoter targeting of the nucleolar remodeling complex component SNF2H without affecting occupancy of the transcription factor UBF and the stress silencers SUV39H1 and SIRT1. During this process, nucleolar localization of UBF and SIRT1 is not altered. On contrary, azacytidine pre-treatment has an adverse effect on rDNA remodeling induced by extract and elicits a stress-type nuclear response. Thus, an early event of Xenopus egg extract-mediated nuclear reprogramming is the remodeling of ribosomal genes involving nucleolar remodeling complex. Condition-specific and rapid silencing of ribosomal genes may serve as a sensitive marker for evaluation of various reprogramming methods.« less

Video Elicitation Interviews: A Qualitative Research Method for Investigating Physician-Patient Interactions

PubMed Central

Henry, Stephen G.; Fetters, Michael D.

2012-01-01

We describe the concept and method of video elicitation interviews and provide practical guidance for primary care researchers who want to use this qualitative method to investigate physician-patient interactions. During video elicitation interviews, researchers interview patients or physicians about a recent clinical interaction using a video recording of that interaction as an elicitation tool. Video elicitation is useful because it allows researchers to integrate data about the content of physician-patient interactions gained from video recordings with data about participants’ associated thoughts, beliefs, and emotions gained from elicitation interviews. This method also facilitates investigation of specific events or moments during interactions. Video elicitation interviews are logistically demanding and time consuming, and they should be reserved for research questions that cannot be fully addressed using either standard interviews or video recordings in isolation. As many components of primary care fall into this category, high-quality video elicitation interviews can be an important method for understanding and improving physician-patient interactions in primary care. PMID:22412003

Video elicitation interviews: a qualitative research method for investigating physician-patient interactions.

PubMed

Henry, Stephen G; Fetters, Michael D

2012-01-01

We describe the concept and method of video elicitation interviews and provide practical guidance for primary care researchers who want to use this qualitative method to investigate physician-patient interactions. During video elicitation interviews, researchers interview patients or physicians about a recent clinical interaction using a video recording of that interaction as an elicitation tool. Video elicitation is useful because it allows researchers to integrate data about the content of physician-patient interactions gained from video recordings with data about participants' associated thoughts, beliefs, and emotions gained from elicitation interviews. This method also facilitates investigation of specific events or moments during interactions. Video elicitation interviews are logistically demanding and time consuming, and they should be reserved for research questions that cannot be fully addressed using either standard interviews or video recordings in isolation. As many components of primary care fall into this category, high-quality video elicitation interviews can be an important method for understanding and improving physician-patient interactions in primary care.

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 Central

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. PMID:24223858

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.

Probability Elicitation Under Severe Time Pressure: A Rank-Based Method.

PubMed

Jaspersen, Johannes G; Montibeller, Gilberto

2015-07-01

Probability elicitation protocols are used to assess and incorporate subjective probabilities in risk and decision analysis. While most of these protocols use methods that have focused on the precision of the elicited probabilities, the speed of the elicitation process has often been neglected. However, speed is also important, particularly when experts need to examine a large number of events on a recurrent basis. Furthermore, most existing elicitation methods are numerical in nature, but there are various reasons why an expert would refuse to give such precise ratio-scale estimates, even if highly numerate. This may occur, for instance, when there is lack of sufficient hard evidence, when assessing very uncertain events (such as emergent threats), or when dealing with politicized topics (such as terrorism or disease outbreaks). In this article, we adopt an ordinal ranking approach from multicriteria decision analysis to provide a fast and nonnumerical probability elicitation process. Probabilities are subsequently approximated from the ranking by an algorithm based on the principle of maximum entropy, a rule compatible with the ordinal information provided by the expert. The method can elicit probabilities for a wide range of different event types, including new ways of eliciting probabilities for stochastically independent events and low-probability events. We use a Monte Carlo simulation to test the accuracy of the approximated probabilities and try the method in practice, applying it to a real-world risk analysis recently conducted for DEFRA (the U.K. Department for the Environment, Farming and Rural Affairs): the prioritization of animal health threats. © 2015 Society for Risk Analysis.

Head movements in low and high gravitoinertial force environments elicit motion sickness - Implications for space motion sickness

NASA Technical Reports Server (NTRS)

Lackner, James R.; Graybiel, Ashton

1987-01-01

Astronauts report that head movements in flight tend to bring on symptoms of space motion sickness (SMS). The effects of head movements in pitch, yaw, and roll (made both with normal vision and with eyes occluded) on susceptibility to motion sickness in the zero G phase of parabolic flight maneuvers were evaluated. The findings are clear-cut: pitch head movements are most provocative, yaw least provocative, and roll intermediate. These experiments suggest that SMS is not a unique nosological entity, but is the consequence of exposure to nonterrestrial force levels. Head movements during departures in either direction from 1 G elicit symptoms.

Amphetamine Elicits Opposing Actions on Readily Releasable and Reserve Pools for Dopamine

PubMed Central

Covey, Dan P.; Juliano, Steven A.; Garris, Paul A.

2013-01-01

Amphetamine, a highly addictive drug with therapeutic efficacy, exerts paradoxical effects on the fundamental communication modes employed by dopamine neurons in modulating behavior. While amphetamine elevates tonic dopamine signaling by depleting vesicular stores and driving non-exocytotic release through reverse transport, this psychostimulant also activates phasic dopamine signaling by up-regulating vesicular dopamine release. We hypothesized that these seemingly incongruent effects arise from amphetamine depleting the reserve pool and enhancing the readily releasable pool. This novel hypothesis was tested using in vivo voltammetry and stimulus trains of varying duration to access different vesicular stores. We show that amphetamine actions are stimulus dependent in the dorsal striatum. Specifically, amphetamine up-regulated vesicular dopamine release elicited by a short-duration train, which interrogates the readily releasable pool, but depleted release elicited by a long-duration train, which interrogates the reserve pool. These opposing actions of vesicular dopamine release were associated with concurrent increases in tonic and phasic dopamine responses. A link between vesicular depletion and tonic signaling was supported by results obtained for amphetamine in the ventral striatum and cocaine in both striatal sub-regions, which demonstrated augmented vesicular release and phasic signals only. We submit that amphetamine differentially targeting dopamine stores reconciles the paradoxical activation of tonic and phasic dopamine signaling. Overall, these results further highlight the unique and region-distinct cellular mechanisms of amphetamine and may have important implications for its addictive and therapeutic properties. PMID:23671560

Gene Expression Profiles of Sporadic Canine Hemangiosarcoma Are Uniquely Associated with Breed

PubMed Central

Tamburini, Beth A.; Trapp, Susan; Phang, Tzu Lip; Schappa, Jill T.; Hunter, Lawrence E.; Modiano, Jaime F.

2009-01-01

The role an individual's genetic background plays on phenotype and biological behavior of sporadic tumors remains incompletely understood. We showed previously that lymphomas from Golden Retrievers harbor defined, recurrent chromosomal aberrations that occur less frequently in lymphomas from other dog breeds, suggesting spontaneous canine tumors provide suitable models to define how heritable traits influence cancer genotypes. Here, we report a complementary approach using gene expression profiling in a naturally occurring endothelial sarcoma of dogs (hemangiosarcoma). Naturally occurring hemangiosarcomas of Golden Retrievers clustered separately from those of non-Golden Retrievers, with contributions from transcription factors, survival factors, and from pro-inflammatory and angiogenic genes, and which were exclusively present in hemangiosarcoma and not in other tumors or normal cells (i.e., they were not due simply to variation in these genes among breeds). Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) was among genes preferentially enriched within known pathways derived from gene set enrichment analysis when characterizing tumors from Golden Retrievers versus other breeds. Heightened VEGFR1 expression in these tumors also was apparent at the protein level and targeted inhibition of VEGFR1 increased proliferation of hemangiosarcoma cells derived from tumors of Golden Retrievers, but not from other breeds. Our results suggest heritable factors mold gene expression phenotypes, and consequently biological behavior in sporadic, naturally occurring tumors. PMID:19461996

Unique and atypical deletions in Prader-Willi syndrome reveal distinct phenotypes.

PubMed

Kim, Soo-Jeong; Miller, Jennifer L; Kuipers, Paul J; German, Jennifer Ruth; Beaudet, Arthur L; Sahoo, Trilochan; Driscoll, Daniel J

2012-03-01

Prader-Willi syndrome (PWS) is a multisystem, contiguous gene disorder caused by an absence of paternally expressed genes within the 15q11.2-q13 region via one of the three main genetic mechanisms: deletion of the paternally inherited 15q11.2-q13 region, maternal uniparental disomy and imprinting defect. The deletion class is typically subdivided into Type 1 and Type 2 based on their proximal breakpoints (BP1-BP3 and BP2-BP3, respectively). Despite PWS being a well-characterized genetic disorder the role of the specific genes contributing to various aspects of the phenotype are not well understood. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) is a recently developed technique that detects copy number changes and aberrant DNA methylation. In this study, we initially applied MS-MLPA to elucidate the deletion subtypes of 88 subjects. In our cohort, 32 had a Type 1 and 49 had a Type 2 deletion. The remaining seven subjects had unique or atypical deletions that were either smaller (n=5) or larger (n=2) than typically described and were further characterized by array-based comparative genome hybridization. In two subjects both the PWS region (15q11.2) and the newly described 15q13.3 microdeletion syndrome region were deleted. The subjects with a unique or an atypical deletion revealed distinct phenotypic features. In conclusion, unique or atypical deletions were found in ∼8% of the deletion subjects with PWS in our cohort. These novel deletions provide further insight into the potential role of several of the genes within the 15q11.2 and the 15q13.3 regions.

Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies

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

Chen, Linxiao; Valentine, Jenny L.; Huang, Chung-Jr

The O-antigen polysaccharide (O-PS) component of lipopolysaccharides on the surface of gram-negative bacteria is both a virulence factor and a B-cell antigen. Antibodies elicited by O-PS often confer protection against infection; therefore, O-PS glycoconjugate vaccines have proven useful against a number of different pathogenic bacteria. However, conventional methods for natural extraction or chemical synthesis of O-PS are technically demanding, inefficient, and expensive. In this paper, we describe an alternative methodology for producing glycoconjugate vaccines whereby recombinant O-PS biosynthesis is coordinated with vesiculation in laboratory strains of Escherichia coli to yield glycosylated outer membrane vesicles (glycOMVs) decorated with pathogen-mimetic glycotopes. Usingmore » this approach, glycOMVs corresponding to eight different pathogenic bacteria were generated. For example, expression of a 17-kb O-PS gene cluster from the highly virulent Francisella tularensis subsp. tularensis (type A) strain Schu S4 in hypervesiculating E. coli cells yielded glycOMVs that displayed F. tularensis O-PS. Immunization of BALB/c mice with glycOMVs elicited significant titers of O-PS–specific serum IgG antibodies as well as vaginal and bronchoalveolar IgA antibodies. Importantly, glycOMVs significantly prolonged survival upon subsequent challenge with F. tularensis Schu S4 and provided complete protection against challenge with two different F. tularensis subsp. holarctica (type B) live vaccine strains, thereby demonstrating the vaccine potential of glycOMVs. Finally, given the ease with which recombinant glycotopes can be expressed on OMVs, the strategy described here could be readily adapted for developing vaccines against many other bacterial pathogens.« less

Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies

DOE PAGES

Chen, Linxiao; Valentine, Jenny L.; Huang, Chung-Jr; ...

2016-06-06

The O-antigen polysaccharide (O-PS) component of lipopolysaccharides on the surface of gram-negative bacteria is both a virulence factor and a B-cell antigen. Antibodies elicited by O-PS often confer protection against infection; therefore, O-PS glycoconjugate vaccines have proven useful against a number of different pathogenic bacteria. However, conventional methods for natural extraction or chemical synthesis of O-PS are technically demanding, inefficient, and expensive. In this paper, we describe an alternative methodology for producing glycoconjugate vaccines whereby recombinant O-PS biosynthesis is coordinated with vesiculation in laboratory strains of Escherichia coli to yield glycosylated outer membrane vesicles (glycOMVs) decorated with pathogen-mimetic glycotopes. Usingmore » this approach, glycOMVs corresponding to eight different pathogenic bacteria were generated. For example, expression of a 17-kb O-PS gene cluster from the highly virulent Francisella tularensis subsp. tularensis (type A) strain Schu S4 in hypervesiculating E. coli cells yielded glycOMVs that displayed F. tularensis O-PS. Immunization of BALB/c mice with glycOMVs elicited significant titers of O-PS–specific serum IgG antibodies as well as vaginal and bronchoalveolar IgA antibodies. Importantly, glycOMVs significantly prolonged survival upon subsequent challenge with F. tularensis Schu S4 and provided complete protection against challenge with two different F. tularensis subsp. holarctica (type B) live vaccine strains, thereby demonstrating the vaccine potential of glycOMVs. Finally, given the ease with which recombinant glycotopes can be expressed on OMVs, the strategy described here could be readily adapted for developing vaccines against many other bacterial pathogens.« less

BHD-associated kidney cancer exhibits unique molecular characteristics and a wide variety of variants in chromatin remodeling genes.

PubMed

Hasumi, Hisashi; Furuya, Mitsuko; Tatsuno, Kenji; Yamamoto, Shogo; Baba, Masaya; Hasumi, Yukiko; Isono, Yasuhiro; Suzuki, Kae; Jikuya, Ryosuke; Otake, Shinji; Muraoka, Kentaro; Osaka, Kimito; Hayashi, Narihiko; Makiyama, Kazuhide; Miyoshi, Yasuhide; Kondo, Keiichi; Nakaigawa, Noboru; Kawahara, Takashi; Izumi, Koji; Teranishi, Junichi; Yumura, Yasushi; Uemura, Hiroji; Nagashima, Yoji; Metwalli, Adam R; Schmidt, Laura S; Aburatani, Hiroyuki; Linehan, W Marston; Yao, Masahiro

2018-05-14

Birt-Hogg-Dubé (BHD) syndrome is a hereditary kidney cancer syndrome, which predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas and pulmonary cysts. The responsible gene FLCN is a tumor suppressor for kidney cancer which plays an important role in energy homeostasis through the regulation of mitochondrial oxidative metabolism. However, the process by which FLCN-deficiency leads to renal tumorigenesis is unclear. In order to clarify molecular pathogenesis of BHD-associated kidney cancer, we conducted whole-exome sequencing analysis using next-generation sequencing technology as well as metabolite analysis using LC/MS and GC/MS. Whole-exome sequencing analysis of BHD-associated kidney cancer revealed that copy number variations (CNV) of BHD-associated kidney cancer are considerably different from those already reported in sporadic cases. In somatic variant analysis, very few variants were commonly observed in BHD-associated kidney cancer; however, variants in chromatin remodeling genes were frequently observed in BHD-associated kidney cancer (17/29 tumors, 59%). Metabolite analysis of BHD-associated kidney cancer revealed metabolic reprogramming towards upregulated redox regulation which may neutralize reactive oxygen species potentially produced from mitochondria with increased respiratory capacity under FLCN-deficiency. BHD-associated kidney cancer displays unique molecular characteristics which are completely different from sporadic kidney cancer, providing mechanistic insight into tumorigenesis under FLCN-deficiency as well as a foundation for development of novel therapeutics for kidney cancer.

Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma

PubMed Central

2012-01-01

Background Esophageal squamous cell carcinoma (ESCC), the predominant histological subtype of esophageal cancer, is characterized by high mortality. Previous work identified important mRNA expression differences between normal and tumor cells; however, to date there are limited ex vivo studies examining expression changes occurring during normal esophageal squamous cell differentiation versus those associated with tumorigenesis. In this study, we used a unique tissue microdissection strategy and microarrays to measure gene expression profiles associated with cell differentiation versus tumorigenesis in twelve cases of patient-matched normal basal squamous epithelial cells (NB), normal differentiated squamous epithelium (ND), and squamous cell cancer. Class comparison and pathway analysis were used to compare NB versus tumor in a search for unique therapeutic targets. Results As a first step towards this goal, gene expression profiles and pathways were evaluated. Overall, ND expression patterns were markedly different from NB and tumor; whereas, tumor and NB were more closely related. Tumor showed a general decrease in differentially expressed genes relative to NB as opposed to ND that exhibited the opposite trend. FSH and IgG networks were most highly dysregulated in normal differentiation and tumorigenesis, respectively. DNA repair pathways were generally elevated in NB and tumor relative to ND indicating involvement in both normal and pathological growth. PDGF signaling pathway and 12 individual genes unique to the tumor/NB comparison were identified as therapeutic targets, and 10 associated ESCC gene-drug pairs were identified. We further examined the protein expression level and the distribution patterns of four genes: ODC1, POSTN, ASPA and IGF2BP3. Ultimately, three genes (ODC1, POSTN, ASPA) were verified to be dysregulated in the same pattern at both the mRNA and protein levels. Conclusions These data reveal insight into genes and molecular pathways mediating

Extinction and renewal of cue-elicited reward-seeking.

PubMed

Bezzina, Louise; Lee, Jessica C; Lovibond, Peter F; Colagiuri, Ben

2016-12-01

Reward cues can contribute to overconsumption of food and drugs and can relapse. The failure of exposure therapies to reduce overconsumption and relapse is generally attributed to the context-specificity of extinction. However, no previous study has examined whether cue-elicited reward-seeking (as opposed to cue-reactivity) is sensitive to context renewal. We tested this possibility in 160 healthy volunteers using a Pavlovian-instrumental transfer (PIT) design involving voluntary responding for a high value natural reward (chocolate). One reward cue underwent Pavlovian extinction in the same (Group AAA) or different context (Group ABA) to all other phases. This cue was compared with a second non-extinguished reward cue and an unpaired control cue. There was a significant overall PIT effect with both reward cues eliciting reward-seeking on test relative to the unpaired cue. Pavlovian extinction substantially reduced this effect, with the extinguished reward cue eliciting less reward-seeking than the non-extinguished reward cue. Most interestingly, extinction of cue-elicited reward-seeking was sensitive to renewal, with extinction less effective for reducing PIT when conducted in a different context. These findings have important implications for extinction-based interventions for reducing maladaptive reward-seeking in practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Introducing Forum Theatre to Elicit and Advocate Children's Views

ERIC Educational Resources Information Center

Hammond, Nick

2013-01-01

Eliciting and advocating the voice of the child remains at the heart of international political agenda and also remains a central role for educational psychologists (EPs). Previous research indicates that EPs tend to use language-based methods for eliciting and advocating views of children. However, these approaches are often limited. Taking a…

The mitochondrial genome of the Japanese skeleton shrimp Caprella mutica (Amphipoda: Caprellidea) reveals a unique gene order and shared apomorphic translocations with Gammaridea.

PubMed

Kilpert, Fabian; Podsiadlowski, Lars

2010-06-01

This study presents the complete mitochondrial (mt) genome of the amphipod Caprella mutica, an east-Asian species, which recently invaded the coastal regions of North America, Europe, and New Zealand. It is the first complete sequence of a member of the amphipod subclade Caprellidea. The mt genome has a total length of 15,427 bp and is organized in a circular double-strand molecule. All 37 mt genes are present, including the common set of 22 tRNAs. Particularly noticeable is the duplication of the control region (CR). The additional CR is located between nad6 and cob, and is almost identical to the original one. The most extensive changes in the gene order affect nad5 and a block consisting of trnH, nad4, nad4L, and trnP-all inserted near the original CR. The gene nad5 is also inverted. Furthermore, a comparison with the pancrustacean ground pattern reveals additional changes of individual tRNA genes. Some of these changes are also shared by Metacrangonyx longipes and Parhyale hawaiensis. These arrangements were found only in amphipods and might be considered as apomorphic by character states of Amphipoda. In all the three species, there is good evidence that trnG originated from a rare duplication/remolding event of the adjacent trnW gene. Nevertheless, each of the three available amphipod mitogenome sequences also bears unique rearrangements. C. mutica, however, shows the most extensive rearrangement in comparison with the pancrustacean ground pattern.

Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

PubMed

Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

2012-10-25

Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in

Primetime for Learning Genes.

PubMed

Keifer, Joyce

2017-02-11

Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene ( BDNF ), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be "poised" for rapid response to activate or repress gene expression depending on environmental stimuli.

Bioinformatic Analyses of Unique (Orphan) Core Genes of the Genus Acidithiobacillus: Functional Inferences and Use As Molecular Probes for Genomic and Metagenomic/Transcriptomic Interrogation.

PubMed

González, Carolina; Lazcano, Marcelo; Valdés, Jorge; Holmes, David S

2016-01-01

Using phylogenomic and gene compositional analyses, five highly conserved gene families have been detected in the core genome of the phylogenetically coherent genus Acidithiobacillus of the class Acidithiobacillia . These core gene families are absent in the closest extant genus Thermithiobacillus tepidarius that subtends the Acidithiobacillus genus and roots the deepest in this class. The predicted proteins encoded by these core gene families are not detected by a BLAST search in the NCBI non-redundant database of more than 90 million proteins using a relaxed cut-off of 1.0e -5 . None of the five families has a clear functional prediction. However, bioinformatic scrutiny, using pI prediction, motif/domain searches, cellular location predictions, genomic context analyses, and chromosome topology studies together with previously published transcriptomic and proteomic data, suggests that some may have functions associated with membrane remodeling during cell division perhaps in response to pH stress. Despite the high level of amino acid sequence conservation within each family, there is sufficient nucleotide variation of the respective genes to permit the use of the DNA sequences to distinguish different species of Acidithiobacillus , making them useful additions to the armamentarium of tools for phylogenetic analysis. Since the protein families are unique to the Acidithiobacillus genus, they can also be leveraged as probes to detect the genus in environmental metagenomes and metatranscriptomes, including industrial biomining operations, and acid mine drainage (AMD).

Genome-wide characterization of vibrio phage ϕpp2 with unique arrangements of the mob-like genes

PubMed Central

2012-01-01

Background Vibrio parahaemolyticus is associated with gastroenteritis, wound infections, and septicemia in human and animals. Phages can control the population of the pathogen. So far, the only one reported genome among giant vibriophages is KVP40: 244,835 bp with 26% coding regions that have T4 homologs. Putative homing endonucleases (HE) were found in Vibrio phage KVP40 bearing one segD and Vibrio cholerae phage ICP1 carrying one mobC/E and one segG. Results A newly isolated Vibrio phage ϕpp2, which was specific to the hosts of V. parahaemolyticus and V. alginolyticus, featured a long nonenveloped head of ~90 × 150 nm and tail of ~110 nm. The phage can survive at 50°C for more than one hour. The genome of the phage ϕpp2 was sequenced to be 246,421 bp, which is 1587 bp larger than KVP40. 383 protein-encoding genes (PEGs) and 30 tRNAs were found in the phage ϕpp2. Between the genomes of ϕpp2 and KVP40, 254 genes including 29 PEGs for viral structure were of high similarity, whereas 17 PEGs of KVP40 and 21 PEGs of ϕpp2 were unmatched. In both genomes, the capsid and tail genes have been identified, as well as the extensive representation of the DNA replication, recombination, and repair enzymes. In addition to the three giant indels of 1098, 1143 and 3330 nt, ϕpp2 possessed unique proteins involved in potassium channel, gp2 (DNA end protector), tRNA nucleotidyltransferase, and mob-type HEs, which were not reported in KVP40. The ϕpp2 PEG274, with strong promoters and translational initiation, was identified to be a mobE type, flanked by NrdA and NrdB/C homologs. Coincidently, several pairs of HE-flanking homologs with empty center were found in the phages of Vibrio phages ϕpp2 and KVP40, as well as in Aeromonas phages (Aeh1 and Ae65), and cyanophage P-SSM2. Conclusions Vibrio phage ϕpp2 was characterized by morphology, growth, and genomics with three giant indels and different types of HEs. The gene analysis on the required elements for transcription

Research Dilemmas Associated with Photo Elicitation in Comparative Early Childhood Education Research

ERIC Educational Resources Information Center

Birkeland, Asta

2013-01-01

Photo elicitation has become an important method to produce data in qualitative research. There is quite an extensive literature indicating the benefits of photo elicitation in order to facilitate collaboration in meaning making between researcher and the interviewee. This article addresses dilemmas associated with using photo elicitation in a…

Tissue underlying the intestinal epithelium elicits proliferation of intestinal stem cells following cytotoxic damage

PubMed Central

Seiler, Kristen M; Schenhals, Erica L; von Furstenberg, Richard J; Allena, Bhavya K; Smith, Brian J; Scaria, Denny; Bresler, Michele N; Dekaney, Christopher M; Henning, Susan J

2015-01-01

The goals of this study were to document the proliferative response of intestinal stem cells (ISCs) during regeneration after damage from doxorubicin (DXR) and to characterize the signals responsible for ISC activation. To this end, jejuni from DXR-treated mice were harvested for histology, assessment of ISC numbers and proliferation by flow cytometry, crypt culture, and RNA analyses. Histology showed that crypt depth and width were increased 4 days after DXR. At this time point, flow cytometry on tissue collected 1 hour after EdU administration revealed increased numbers of CD24loUEA− ISCs and increased percentage of ISCs cycling. In culture, crypts harvested from DXR-treated mice were equally proliferative as those of control mice. Addition of subepithelial intestinal tissue (SET) collected 4 days after DXR elicited increased budding (1.4 ± 0.3 vs. 5.1 ± 1.0 buds per enteroid). Microarray analysis of SET collected 4 days after DXR revealed 1,030 differentially expressed transcripts. Cross comparison of Gene Ontology terms considered relevant to ISC activation pointed to 10 candidate genes. Of these the epidermal growth factor (EGF) family member amphiregulin and the BMP antagonist chordin-like 2 were chosen for further study. In crypt culture, amphiregulin alone did not elicit significant budding, but amphiregulin in combination with BMP antagonism showed marked synergism (yielding 6.3 ± 0.5 buds per enteroid). These data suggest a critical role for underlying tissue in regulating ISC behavior after damage, and point to synergism between amphiregulin and chordin-like 2 as factors which may account for activation of ISCs in the regenerative phase. PMID:25693894

Avirulence gene mapping in the Hessian fly (Mayetiola destructor) reveals a protein phosphatase 2C effector gene family

USDA-ARS?s Scientific Manuscript database

The genetic tractability of the Hessian fly (HF, Mayetiola destructor) provides an opportunity to investigate the mechanisms insects use to induce plant gall formation. Here we demonstrate that capacity using the newly sequenced HF genome to identify the gene (vH24) that elicits the effector-trigger...

A subset of IL-10-producing gammadelta T cells protect the liver from Listeria-elicited, CD8(+) T cell-mediated injury.

PubMed

Rhodes, Katherine A; Andrew, Elizabeth M; Newton, Darren J; Tramonti, Daniela; Carding, Simon R

2008-08-01

Although gammadelta T cells play a role in protecting tissues from pathogen-elicited damage to bacterial, viral and parasitic pathogens, the mechanisms involved in the damage and in the protection have not been clearly elucidated. This has been addressed using a murine model of listeriosis, which in mice lacking gammadelta T cells (TCRdelta(-/-)) is characterised by severe and extensive immune-mediated hepatic necrosis. We show that these hepatic lesions are caused by Listeria-elicited CD8(+) T cells secreting high levels of TNF-alpha that accumulate in the liver of Listeria-infected TCRdelta(-/-) mice. Using isolated populations of gammadelta T cells from wild-type and cytokine-deficient strains of mice to reconstitute TCRdelta(-/-) mice, the TCR variable gene 4 (Vgamma4)(+) subset of gammadelta T cells was shown to protect against liver injury. Hepatoprotection was dependent upon their ability to produce IL-10 after TCR-mediated interactions with Listeria-elicited macrophages and CD8(+) T cells. IL-10-producing Vgamma4(+) T cells also contribute to controlling CD8(+) T cell expansion and to regulating and reducing TNF-alpha secretion by activated CD8(+) T cells. This effect on TNF-alpha production was directly attributed to IL-10. These findings identify a novel mechanism by which pathogen-elicited CD8(+) T cells are regulated via interactions with, and activation of, IL-10-producing hepatoprotective gammadelta T cells.

A nonproliferating parvovirus vaccine vector elicits sustained, protective humoral immunity following a single intravenous or intranasal inoculation.

PubMed

Palmer, Gene A; Brogdon, Jennifer L; Constant, Stephanie L; Tattersall, Peter

2004-02-01

An ideal vaccine delivery system would elicit persistent protection following a single administration, preferably by a noninvasive route, and be safe even in the face of immunosuppression, either inherited or acquired, of the recipient. We have exploited the unique life cycle of the autonomous parvoviruses to develop a nonproliferating vaccine platform that appears to both induce priming and continually boost a protective immune response following a single inoculation. A crippled parvovirus vector was constructed, based on a chimera between minute virus of mice (MVM) and LuIII, which expresses Borrelia burgdorferi outer surface protein A (OspA) instead of its coat protein. The vector was packaged into an MVM lymphotropic capsid and inoculated into naive C3H/HeNcr mice. Vaccination with a single vector dose, either intravenously or intranasally, elicited high-titer anti-OspA-specific antibody that provided protection from live spirochete challenge and was sustained over the lifetime of the animal. Both humoral and cell-mediated Th(1) immunity was induced, as shown by anti-OspA immunoglobulin G2a antibody and preferential gamma interferon production by OspA-specific CD4(+) T cells.

A Nonproliferating Parvovirus Vaccine Vector Elicits Sustained, Protective Humoral Immunity following a Single Intravenous or Intranasal Inoculation

PubMed Central

Palmer, Gene A.; Brogdon, Jennifer L.; Constant, Stephanie L.; Tattersall, Peter

2004-01-01

An ideal vaccine delivery system would elicit persistent protection following a single administration, preferably by a noninvasive route, and be safe even in the face of immunosuppression, either inherited or acquired, of the recipient. We have exploited the unique life cycle of the autonomous parvoviruses to develop a nonproliferating vaccine platform that appears to both induce priming and continually boost a protective immune response following a single inoculation. A crippled parvovirus vector was constructed, based on a chimera between minute virus of mice (MVM) and LuIII, which expresses Borrelia burgdorferi outer surface protein A (OspA) instead of its coat protein. The vector was packaged into an MVM lymphotropic capsid and inoculated into naive C3H/HeNcr mice. Vaccination with a single vector dose, either intravenously or intranasally, elicited high-titer anti-OspA-specific antibody that provided protection from live spirochete challenge and was sustained over the lifetime of the animal. Both humoral and cell-mediated Th1 immunity was induced, as shown by anti-OspA immunoglobulin G2a antibody and preferential gamma interferon production by OspA-specific CD4+ T cells. PMID:14722265

Unique and atypical deletions in Prader–Willi syndrome reveal distinct phenotypes

PubMed Central

Kim, Soo-Jeong; Miller, Jennifer L; Kuipers, Paul J; German, Jennifer Ruth; Beaudet, Arthur L; Sahoo, Trilochan; Driscoll, Daniel J

2012-01-01

Prader–Willi syndrome (PWS) is a multisystem, contiguous gene disorder caused by an absence of paternally expressed genes within the 15q11.2-q13 region via one of the three main genetic mechanisms: deletion of the paternally inherited 15q11.2-q13 region, maternal uniparental disomy and imprinting defect. The deletion class is typically subdivided into Type 1 and Type 2 based on their proximal breakpoints (BP1–BP3 and BP2–BP3, respectively). Despite PWS being a well-characterized genetic disorder the role of the specific genes contributing to various aspects of the phenotype are not well understood. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) is a recently developed technique that detects copy number changes and aberrant DNA methylation. In this study, we initially applied MS-MLPA to elucidate the deletion subtypes of 88 subjects. In our cohort, 32 had a Type 1 and 49 had a Type 2 deletion. The remaining seven subjects had unique or atypical deletions that were either smaller (n=5) or larger (n=2) than typically described and were further characterized by array-based comparative genome hybridization. In two subjects both the PWS region (15q11.2) and the newly described 15q13.3 microdeletion syndrome region were deleted. The subjects with a unique or an atypical deletion revealed distinct phenotypic features. In conclusion, unique or atypical deletions were found in ∼8% of the deletion subjects with PWS in our cohort. These novel deletions provide further insight into the potential role of several of the genes within the 15q11.2 and the 15q13.3 regions. PMID:22045295

Issues in Requirements Elicitation

DTIC Science & Technology

1992-09-01

oriented domain analysis ( FODA ) continues that the re- quirements analyst uses the products of domain analysis when implementing a new system [Kang 90, p...Peterson, A. Spencer. Feature-Oriented Domain Analysis ( FODA ) Feasibility Study. Technical Report CMU/SEI-90-TR-21, ADA235785, Software Engineering...3.3 Problems of Volatility 12 4 Current Elicitation Techniques 15 4.1 Information Gathering 16 4.2 Requirements Expression and Analysis 19 4.3

Videos of conspecifics elicit interactive looking patterns and facial expressions in monkeys

PubMed Central

Mosher, Clayton P.; Zimmerman, Prisca E.; Gothard, Katalin M.

2014-01-01

A broader understanding of the neural basis of social behavior in primates requires the use of species-specific stimuli that elicit spontaneous, but reproducible and tractable behaviors. In this context of natural behaviors, individual variation can further inform about the factors that influence social interactions. To approximate natural social interactions similar to those documented by field studies, we used unedited video footage to induce in viewer monkeys spontaneous facial expressions and looking patterns in the laboratory setting. Three adult male monkeys, previously behaviorally and genetically (5-HTTLPR) characterized (Gibboni et al., 2009), were monitored while they watched 10 s video segments depicting unfamiliar monkeys (movie monkeys) displaying affiliative, neutral, and aggressive behaviors. The gaze and head orientation of the movie monkeys alternated between ‘averted’ and ‘directed’ at the viewer. The viewers were not reinforced for watching the movies, thus their looking patterns indicated their interest and social engagement with the stimuli. The behavior of the movie monkey accounted for differences in the looking patterns and facial expressions displayed by the viewers. We also found multiple significant differences in the behavior of the viewers that correlated with their interest in these stimuli. These socially relevant dynamic stimuli elicited spontaneous social behaviors, such as eye-contact induced reciprocation of facial expression, gaze aversion, and gaze following, that were previously not observed in response to static images. This approach opens a unique opportunity to understanding the mechanisms that trigger spontaneous social behaviors in humans and non-human primates. PMID:21688888

Videos of conspecifics elicit interactive looking patterns and facial expressions in monkeys.

PubMed

Mosher, Clayton P; Zimmerman, Prisca E; Gothard, Katalin M

2011-08-01

A broader understanding of the neural basis of social behavior in primates requires the use of species-specific stimuli that elicit spontaneous, but reproducible and tractable behaviors. In this context of natural behaviors, individual variation can further inform about the factors that influence social interactions. To approximate natural social interactions similar to those documented by field studies, we used unedited video footage to induce in viewer monkeys spontaneous facial expressions and looking patterns in the laboratory setting. Three adult male monkeys (Macaca mulatta), previously behaviorally and genetically (5-HTTLPR) characterized, were monitored while they watched 10 s video segments depicting unfamiliar monkeys (movie monkeys) displaying affiliative, neutral, and aggressive behaviors. The gaze and head orientation of the movie monkeys alternated between "averted" and "directed" at the viewer. The viewers were not reinforced for watching the movies, thus their looking patterns indicated their interest and social engagement with the stimuli. The behavior of the movie monkey accounted for differences in the looking patterns and facial expressions displayed by the viewers. We also found multiple significant differences in the behavior of the viewers that correlated with their interest in these stimuli. These socially relevant dynamic stimuli elicited spontaneous social behaviors, such as eye-contact induced reciprocation of facial expression, gaze aversion, and gaze following, that were previously not observed in response to static images. This approach opens a unique opportunity to understanding the mechanisms that trigger spontaneous social behaviors in humans and nonhuman primates. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

A new method for eliciting three speaking styles in the laboratory

PubMed Central

Harnsberger, James D.; Wright, Richard; Pisoni, David B.

2009-01-01

In this study, a method was developed to elicit three different speaking styles, reduced, citation, and hyperarticulated, using controlled sentence materials in a laboratory setting. In the first set of experiments, the reduced style was elicited by having twelve talkers read a sentence while carrying out a distractor task that involved recalling from short-term memory an individually-calibrated number of digits. The citation style corresponded to read speech in the laboratory. The hyperarticulated style was elicited by prompting talkers (twice) to reread the sentences more carefully. The results of perceptual tests with naïve listeners and an acoustic analysis showed that six of the twelve talkers produced a reduced style of speech for the test sentences in the distractor task relative to the same sentences in the citation style condition. In addition, all talkers consistently produced sentences in the citation and hyperarticulated styles. In the second set of experiments, the reduced style was elicited by increasing the number of digits in the distractor task by one (a heavier cognitive load). The procedures for eliciting citation and hyperarticulated sentences remained unchanged. Ten talkers were recorded in the second experiment. The results showed that six out of ten talkers differentiated all three styles as predicted (70% of all sentences recorded). In addition, all talkers consistently produced sentences in the citation and hyperarticulated styles. Overall, the results demonstrate that it is possible to elicit controlled sentence stimulus materials varying in speaking style in a laboratory setting, although the method requires further refinement to elicit these styles more consistently from individual participants. PMID:19562041

A new method for eliciting three speaking styles in the laboratory.

PubMed

Harnsberger, James D; Wright, Richard; Pisoni, David B

2008-04-01

In this study, a method was developed to elicit three different speaking styles, reduced, citation, and hyperarticulated, using controlled sentence materials in a laboratory setting. In the first set of experiments, the reduced style was elicited by having twelve talkers read a sentence while carrying out a distractor task that involved recalling from short-term memory an individually-calibrated number of digits. The citation style corresponded to read speech in the laboratory. The hyperarticulated style was elicited by prompting talkers (twice) to reread the sentences more carefully. The results of perceptual tests with naïve listeners and an acoustic analysis showed that six of the twelve talkers produced a reduced style of speech for the test sentences in the distractor task relative to the same sentences in the citation style condition. In addition, all talkers consistently produced sentences in the citation and hyperarticulated styles. In the second set of experiments, the reduced style was elicited by increasing the number of digits in the distractor task by one (a heavier cognitive load). The procedures for eliciting citation and hyperarticulated sentences remained unchanged. Ten talkers were recorded in the second experiment. The results showed that six out of ten talkers differentiated all three styles as predicted (70% of all sentences recorded). In addition, all talkers consistently produced sentences in the citation and hyperarticulated styles. Overall, the results demonstrate that it is possible to elicit controlled sentence stimulus materials varying in speaking style in a laboratory setting, although the method requires further refinement to elicit these styles more consistently from individual participants.

Molecular and Biochemical Characterization of a Cathepsin B-Like Protease Family Unique to Trypanosoma congolense▿ †

PubMed Central

Mendoza-Palomares, Carlos; Biteau, Nicolas; Giroud, Christiane; Coustou, Virginie; Coetzer, Theresa; Authié, Edith; Boulangé, Alain; Baltz, Théo

2008-01-01

Cysteine proteases have been shown to be essential virulence factors and drug targets in trypanosomatids and an attractive antidisease vaccine candidate for Trypanosoma congolense. Here, we describe an important amplification of genes encoding cathepsin B-like proteases unique to T. congolense. More than 13 different genes were identified, whereas only one or two highly homologous genes have been identified in other trypanosomatids. These proteases grouped into three evolutionary clusters: TcoCBc1 to TcoCBc5 and TcoCBc6, which possess the classical catalytic triad (Cys, His, and Asn), and TcoCBs7 to TcoCBs13, which contains an unusual catalytic site (Ser, Xaa, and Asn). Expression profiles showed that members of the TcoCBc1 to TcoCBc5 and the TcoCBs7 to TcoCBs13 groups are expressed mainly in bloodstream forms and localize in the lysosomal compartment. The expression of recombinant representatives of each group (TcoCB1, TcoCB6, and TcoCB12) as proenzymes showed that TcoCBc1 and TcoCBc6 are able to autocatalyze their maturation 21 and 31 residues, respectively, upstream of the predicted start of the catalytic domain. Both displayed a carboxydipeptidase function, while only TcoCBc1 behaved as an endopeptidase. TcoCBc1 exhibited biochemical differences regarding inhibitor sensitivity compared to that of other cathepsin B-like proteases. Recombinant pro-TcoCBs12 did not automature in vitro, and the pepsin-matured enzyme was inactive in tests with cathepsin B fluorogenic substrates. In vivo inhibition studies using CA074Me (a cell-permeable cathepsin B-specific inhibitor) demonstrated that TcoCB are involved in lysosomal protein degradation essential for survival in bloodstream form. Furthermore, TcoCBc1 elicited an important immune response in experimentally infected cattle. We propose this family of proteins as a potential therapeutic target and as a plausible antigen for T. congolense diagnosis. PMID:18281598

Physiological responses induced by emotion-eliciting films.

PubMed

Fernández, Cristina; Pascual, Juan C; Soler, Joaquim; Elices, Matilde; Portella, Maria J; Fernández-Abascal, Enrique

2012-06-01

Emotion-eliciting films are commonly used to evoke subjective emotional responses in experimental settings. The main aim of the present study was to investigate whether a set of film clips with discrete emotions were capable to elicit measurable objective physiological responses. The convergence between subjective and objective measures was evaluated. Finally, the effect of gender on emotional responses was investigated. A sample of 123 subjects participated in the study. Individuals were asked to view a set of emotional film clips capable to induce seven emotions: anger, fear, sadness, disgust, amusement, tenderness and neutral state. Skin conductance level (SCL), heart rate (HR) and subjective emotional responses were measured for each film clip. In comparison with neutral films, SCL was significantly increased after viewing fear films, and HR was also significantly incremented for anger and fear films. Physiological variations were associated with arousal measures indicating a convergence between subjective and objective reactions. Women appeared to display significantly greater SCL and HR responses for films inducing sadness. The findings suggest that physiological activation would be more easily induced by emotion-eliciting films that tap into emotions with higher subjective arousal such as anger and fear.

Do community and autonomy moral violations elicit different emotions?

PubMed

Kollareth, Dolichan; Kikutani, Mariko; Shirai, Mariko; Russell, James A

2018-06-11

According to one important set of theories, different domains of immorality are linked to different discrete emotions-panculturally. Violations against the community elicit contempt, whereas violations against an individual elicit anger. To test this theory, American, Indian and Japanese participants (N = 480) indicated contempt and anger reactions (with verbal rating and face selection) to both the types of immorality. To remedy method problems in previous research, community and autonomy violations were created for the same story-frame, by varying the target to be either the community or an individual. Community and autonomy violations did not differ significantly in the emotion elicited: overall, both types of violations elicited more anger than contempt (and more negative emotion of any kind than positive emotion). By verbal rating, Americans and Indians reported more anger than contempt for both types of violation, whereas Japanese reported more contempt than anger for both types. By face selection, the three cultural groups selected anger more than contempt for both types of violation. The results speak against defining distinct domains of morality by their association with distinct emotions. © 2018 International Union of Psychological Science.

Film clips and narrative text as subjective emotion elicitation techniques.

PubMed

Zupan, Barbra; Babbage, Duncan R

2017-01-01

Film clips and narrative text are useful techniques in eliciting emotion in a laboratory setting but have not been examined side-by-side using the same methodology. This study examined the self-identification of emotions elicited by film clip and narrative text stimuli to confirm that selected stimuli appropriately target the intended emotions. Seventy participants viewed 30 film clips, and 40 additional participants read 30 narrative texts. Participants identified the emotion experienced (happy, sad, angry, fearful, neutral-six stimuli each). Eighty-five percent of participants self-identified the target emotion for at least two stimuli for all emotion categories of film clips, except angry (only one) and for all categories of narrative text, except fearful (only one). The most effective angry text was correctly identified 74% of the time. Film clips were more effective in eliciting all target emotions in participants for eliciting the correct emotion (angry), intensity rating (happy, sad), or both (fearful).

National-level long-term eruption forecasts by expert elicitation

NASA Astrophysics Data System (ADS)

Bebbington, Mark S.; Stirling, Mark W.; Cronin, Shane; Wang, Ting; Jolly, Gill

2018-06-01

Volcanic hazard estimation is becoming increasingly quantitative, creating the potential for land-use decisions and engineering design to use volcanic information in an analogous manner to seismic codes. The initial requirement is to characterize the possible hazard sources, quantifying the likely timing, magnitude and location of the next eruption in each case. This is complicated by the extremely different driving processes at individual volcanoes, and incomplete and uneven records of past activity at various volcanoes. To address these issues, we carried out an expert elicitation approach to estimate future eruption potential for 12 volcanoes of interest in New Zealand. A total of 28 New Zealand experts provided estimates that were combined using Cooke's classical method to arrive at a hazard estimate. In 11 of the 12 cases, the elicited eruption duration increased with VEI, and was correlated with expected repose, differing little between volcanoes. Most of the andesitic volcanoes had very similar elicited distributions for the VEI of a future eruption, except that Taranaki was expected to produce a larger eruption, due to the current long repose. Elicited future vent locations for Tongariro and Okataina reflect strongly the most recent eruptions. In the poorly studied Bay of Islands volcanic field, the estimated vent location distribution was centred on the centroid of the previous vent locations, while in the Auckland field, it was focused on regions within the field without past eruptions. The elicited median dates for the next eruptions ranged from AD2022 (Whakaari/White Island) to AD4390 (Tuhua/Mayor Island).

Bioinformatic Analyses of Unique (Orphan) Core Genes of the Genus Acidithiobacillus: Functional Inferences and Use As Molecular Probes for Genomic and Metagenomic/Transcriptomic Interrogation

PubMed Central

González, Carolina; Lazcano, Marcelo; Valdés, Jorge; Holmes, David S.

2016-01-01

Using phylogenomic and gene compositional analyses, five highly conserved gene families have been detected in the core genome of the phylogenetically coherent genus Acidithiobacillus of the class Acidithiobacillia. These core gene families are absent in the closest extant genus Thermithiobacillus tepidarius that subtends the Acidithiobacillus genus and roots the deepest in this class. The predicted proteins encoded by these core gene families are not detected by a BLAST search in the NCBI non-redundant database of more than 90 million proteins using a relaxed cut-off of 1.0e−5. None of the five families has a clear functional prediction. However, bioinformatic scrutiny, using pI prediction, motif/domain searches, cellular location predictions, genomic context analyses, and chromosome topology studies together with previously published transcriptomic and proteomic data, suggests that some may have functions associated with membrane remodeling during cell division perhaps in response to pH stress. Despite the high level of amino acid sequence conservation within each family, there is sufficient nucleotide variation of the respective genes to permit the use of the DNA sequences to distinguish different species of Acidithiobacillus, making them useful additions to the armamentarium of tools for phylogenetic analysis. Since the protein families are unique to the Acidithiobacillus genus, they can also be leveraged as probes to detect the genus in environmental metagenomes and metatranscriptomes, including industrial biomining operations, and acid mine drainage (AMD). PMID:28082953

Colloquium paper: uniquely human evolution of sialic acid genetics and biology.

PubMed

Varki, Ajit

2010-05-11

Darwinian evolution of humans from our common ancestors with nonhuman primates involved many gene-environment interactions at the population level, and the resulting human-specific genetic changes must contribute to the "Human Condition." Recent data indicate that the biology of sialic acids (which directly involves less than 60 genes) shows more than 10 uniquely human genetic changes in comparison with our closest evolutionary relatives. Known outcomes are tissue-specific changes in abundant cell-surface glycans, changes in specificity and/or expression of multiple proteins that recognize these glycans, and novel pathogen regimes. Specific events include Alu-mediated inactivation of the CMAH gene, resulting in loss of synthesis of the Sia N-glycolylneuraminic acid (Neu5Gc) and increase in expression of the precursor N-acetylneuraminic acid (Neu5Ac); increased expression of alpha2-6-linked Sias (likely because of changed expression of ST6GALI); and multiple changes in SIGLEC genes encoding Sia-recognizing Ig-like lectins (Siglecs). The last includes binding specificity changes (in Siglecs -5, -7, -9, -11, and -12); expression pattern changes (in Siglecs -1, -5, -6, and -11); gene conversion (SIGLEC11); and deletion or pseudogenization (SIGLEC13, SIGLEC14, and SIGLEC16). A nongenetic outcome of the CMAH mutation is human metabolic incorporation of foreign dietary Neu5Gc, in the face of circulating anti-Neu5Gc antibodies, generating a novel "xeno-auto-antigen" situation. Taken together, these data suggest that both the genes associated with Sia biology and the related impacts of the environment comprise a relative "hot spot" of genetic and physiological changes in human evolution, with implications for uniquely human features both in health and disease.

Comparative fecal metagenomics unveils unique functional capacity of the swine gut

PubMed Central

2011-01-01

Background Uncovering the taxonomic composition and functional capacity within the swine gut microbial consortia is of great importance to animal physiology and health as well as to food and water safety due to the presence of human pathogens in pig feces. Nonetheless, limited information on the functional diversity of the swine gut microbiome is available. Results Analysis of 637, 722 pyrosequencing reads (130 megabases) generated from Yorkshire pig fecal DNA extracts was performed to help better understand the microbial diversity and largely unknown functional capacity of the swine gut microbiome. Swine fecal metagenomic sequences were annotated using both MG-RAST and JGI IMG/M-ER pipelines. Taxonomic analysis of metagenomic reads indicated that swine fecal microbiomes were dominated by Firmicutes and Bacteroidetes phyla. At a finer phylogenetic resolution, Prevotella spp. dominated the swine fecal metagenome, while some genes associated with Treponema and Anareovibrio species were found to be exclusively within the pig fecal metagenomic sequences analyzed. Functional analysis revealed that carbohydrate metabolism was the most abundant SEED subsystem, representing 13% of the swine metagenome. Genes associated with stress, virulence, cell wall and cell capsule were also abundant. Virulence factors associated with antibiotic resistance genes with highest sequence homology to genes in Bacteroidetes, Clostridia, and Methanosarcina were numerous within the gene families unique to the swine fecal metagenomes. Other abundant proteins unique to the distal swine gut shared high sequence homology to putative carbohydrate membrane transporters. Conclusions The results from this metagenomic survey demonstrated the presence of genes associated with resistance to antibiotics and carbohydrate metabolism suggesting that the swine gut microbiome may be shaped by husbandry practices. PMID:21575148

Mrt, a Gene Unique to Fungi, Encodes an Oligosaccharide Transporter and Facilitates Rhizosphere Competency in Metarhizium robertsii1[C][W

PubMed Central

Fang, Weiguo; St. Leger, Raymond J.

2010-01-01

The symbiotic associations between rhizospheric fungi and plants have enormous environmental impact. Fungi are crucial to plant health as antagonists of pathogens and herbivores and facilitate the uptake of soil nutrients. However, little is known about the plant products obtained by fungi in exchange or how they are transported through the symbiotic interface. Here, we demonstrate that sucrose and raffinose family oligosaccharides in root exudates are important for rhizosphere competence in the insect pathogen Metarhizium robertsii (formerly known as Metarhizium anisopliae). We identified mutants in the Metarhizium raffinose transporter (Mrt) gene of M. robertsii that grew poorly in root exudate and were greatly reduced in rhizosphere competence on grass roots. Studies on sugar uptake, including competition assays, revealed that MRT was a sucrose and galactoside transporter. Disrupting MRT resulted in greatly reduced or no growth on sucrose and galactosides but did not affect growth on monosaccharides or oligosaccharides composed entirely of glucose subunits. Consistent with this, expression of Mrt is exclusively up-regulated by galactosides and sucrose. Expressing a green fluorescent protein gene under the control of the Mrt promoter confirmed that MRT was expressed by germlings in the vicinity of grass roots but not in surrounding bulk soil. Disrupting Mrt did not reduce virulence to insects, demonstrating that Mrt is exclusively involved in M. robertsii’s interactions with plants. To our knowledge, MRT is the first oligosaccharide transporter identified and characterized in a fungus and is unique to filamentous fungi, but homologous genes in Magnaporthe, Ustilago, Aspergillus, Fusarium, Epichloe, and Penicillium species indicate that oligosaccharide transport is of widespread significance. PMID:20837701

Common and unique elements of the ABA-regulated transcriptome of Arabidopsis guard cells

PubMed Central

2011-01-01

Background In the presence of drought and other desiccating stresses, plants synthesize and redistribute the phytohormone abscisic acid (ABA). ABA promotes plant water conservation by acting on specialized cells in the leaf epidermis, guard cells, which border and regulate the apertures of stomatal pores through which transpirational water loss occurs. Following ABA exposure, solute uptake into guard cells is rapidly inhibited and solute loss is promoted, resulting in inhibition of stomatal opening and promotion of stomatal closure, with consequent plant water conservation. There is a wealth of information on the guard cell signaling mechanisms underlying these rapid ABA responses. To investigate ABA regulation of gene expression in guard cells in a systematic genome-wide manner, we analyzed data from global transcriptomes of guard cells generated with Affymetrix ATH1 microarrays, and compared these results to ABA regulation of gene expression in leaves and other tissues. Results The 1173 ABA-regulated genes of guard cells identified by our study share significant overlap with ABA-regulated genes of other tissues, and are associated with well-defined ABA-related promoter motifs such as ABREs and DREs. However, we also computationally identified a unique cis-acting motif, GTCGG, associated with ABA-induction of gene expression specifically in guard cells. In addition, approximately 300 genes showing ABA-regulation unique to this cell type were newly uncovered by our study. Within the ABA-regulated gene set of guard cells, we found that many of the genes known to encode ion transporters associated with stomatal opening are down-regulated by ABA, providing one mechanism for long-term maintenance of stomatal closure during drought. We also found examples of both negative and positive feedback in the transcriptional regulation by ABA of known ABA-signaling genes, particularly with regard to the PYR/PYL/RCAR class of soluble ABA receptors and their downstream targets

Eliciting interval beliefs: An experimental study

PubMed Central

Peeters, Ronald; Wolk, Leonard

2017-01-01

In this paper we study the interval scoring rule as a mechanism to elicit subjective beliefs under varying degrees of uncertainty. In our experiment, subjects forecast the termination time of a time series to be generated from a given but unknown stochastic process. Subjects gradually learn more about the underlying process over time and hence the true distribution over termination times. We conduct two treatments, one with a high and one with a low volatility process. We find that elicited intervals are better when subjects are facing a low volatility process. In this treatment, participants learn to position their intervals almost optimally over the course of the experiment. This is in contrast with the high volatility treatment, where subjects, over the course of the experiment, learn to optimize the location of their intervals but fail to provide the optimal length. PMID:28380020

A comparison of two methods for expert elicitation in health technology assessments.

PubMed

Grigore, Bogdan; Peters, Jaime; Hyde, Christopher; Stein, Ken

2016-07-26

When data needed to inform parameters in decision models are lacking, formal elicitation of expert judgement can be used to characterise parameter uncertainty. Although numerous methods for eliciting expert opinion as probability distributions exist, there is little research to suggest whether one method is more useful than any other method. This study had three objectives: (i) to obtain subjective probability distributions characterising parameter uncertainty in the context of a health technology assessment; (ii) to compare two elicitation methods by eliciting the same parameters in different ways; (iii) to collect subjective preferences of the experts for the different elicitation methods used. Twenty-seven clinical experts were invited to participate in an elicitation exercise to inform a published model-based cost-effectiveness analysis of alternative treatments for prostate cancer. Participants were individually asked to express their judgements as probability distributions using two different methods - the histogram and hybrid elicitation methods - presented in a random order. Individual distributions were mathematically aggregated across experts with and without weighting. The resulting combined distributions were used in the probabilistic analysis of the decision model and mean incremental cost-effectiveness ratios and the expected values of perfect information (EVPI) were calculated for each method, and compared with the original cost-effectiveness analysis. Scores on the ease of use of the two methods and the extent to which the probability distributions obtained from each method accurately reflected the expert's opinion were also recorded. Six experts completed the task. Mean ICERs from the probabilistic analysis ranged between £162,600-£175,500 per quality-adjusted life year (QALY) depending on the elicitation and weighting methods used. Compared to having no information, use of expert opinion decreased decision uncertainty: the EVPI value at the £30

Dose- and Time-Dependent Transcriptional Response of Ishikawa Cells Exposed to Genistein

PubMed Central

Naciff, Jorge M.; Khambatta, Zubin S.; Carr, Gregory J.; Tiesman, Jay P.; Singleton, David W.; Khan, Sohaib A.; Daston, George P.

2016-01-01

To further define the utility of the Ishikawa cells as a reliable in vitro model to determine the potential estrogenic activity of chemicals of interest, transcriptional changes induced by genistein (GES) in Ishikawa cells at various doses (10 pM, 1 nM, 100 nM, and 10 μM) and time points (8, 24, and 48 h) were identified using a comprehensive microarray approach. Trend analysis indicated that the expression of 5342 unique genes was modified by GES in a dose- and time-dependent manner (P ≤ 0.0001). However, the majority of gene expression changes induced in Ishikawa cells were elicited by the highest dose of GES evaluated (10 μM). The GES’ estrogenic activity was identified by comparing the Ishikawa cells’ response to GES versus 17 α-ethynyl estradiol (EE, at equipotent doses, ie, 10 μM vs 1 μM, respectively) and was defined by changes in the expression of 284 unique genes elicited by GES and EE in the same direction, although the magnitude of the change for some genes was different. Further, comparing the response of the Ishikawa cells exposed to high doses of GES and EE versus the response of the juvenile rat uterus exposed to EE, we identified 66 unique genes which were up- or down regulated in a similar manner in vivo as well as in vitro. Genistein elicits changes in multiple molecular pathways affecting various biological processes particularly associated with cell organization and biogenesis, regulation of translation, cell proliferation, and intracellular transport; processes also affected by estrogen exposure in the uterus of the rat. These results indicate that Ishikawa cells are capable of generating a biologically relevant estrogenic response and offer an in vitro model to assess this mode of action. PMID:26865667

TRAC-Monterey FY16 Work Program Development and Report of Research Elicitation

DTIC Science & Technology

2016-01-01

any changes to priorities or additional projects that require immediate research. Work Program; Research Elicitation Unclassified UU UU UU UU 35 MAJ...conduct analysis for the Army. 1 Marks, Chris, Nesbitt, Peter. TRAC FY14 Research Requirements Elicitation . Technical Report TRAC-M-TM-13-059. 700 Dyer... Requirements Elicitation Interviews Interview Guide: 1. Describe a research requirement in the areas of topics, techniques, and methodologies. 2

Pattern visual evoked potentials elicited by organic electroluminescence screen.

PubMed

Matsumoto, Celso Soiti; Shinoda, Kei; Matsumoto, Harue; Funada, Hideaki; Sasaki, Kakeru; Minoda, Haruka; Iwata, Takeshi; Mizota, Atsushi

2014-01-01

To determine whether organic electroluminescence (OLED) screens can be used as visual stimulators to elicit pattern-reversal visual evoked potentials (p-VEPs). Checkerboard patterns were generated on a conventional cathode-ray tube (S710, Compaq Computer Co., USA) screen and on an OLED (17 inches, 320 × 230 mm, PVM-1741, Sony, Tokyo, Japan) screen. The time course of the luminance changes of each monitor was measured with a photodiode. The p-VEPs elicited by these two screens were recorded from 15 eyes of 9 healthy volunteers (22.0 ± 0.8 years). The OLED screen had a constant time delay from the onset of the trigger signal to the start of the luminescence change. The delay during the reversal phase from black to white for the pattern was 1.0 msec on the cathode-ray tube (CRT) screen and 0.5 msec on the OLED screen. No significant differences in the amplitudes of P100 and the implicit times of N75 and P100 were observed in the p-VEPs elicited by the CRT and the OLED screens. The OLED screen can be used as a visual stimulator to elicit p-VEPs; however the time delay and the specific properties in the luminance change must be taken into account.

Practical Guidance and Ethical Considerations for Studies Using Photo-Elicitation Interviews

PubMed Central

Bugos, Eva; Frasso, Rosemary; FitzGerald, Elizabeth; True, Gala; Adachi-Mejia, Anna M.

2014-01-01

Photo-elicitation is a qualitative interviewing technique that has gained popularity in recent years. It is the foundation for photovoice projects and is a tool well-suited for community-based participatory research. Photo-elicitation yields rich data, and interview participants say these interviews encourage community awareness and engagement. This article draws on 9 studies, conducted by researchers at 3 institutions (the University of Pennsylvania, the Philadelphia Veterans Affairs Medical Center, and the Geisel School of Medicine at Dartmouth) in partnership with community-based organizations and students, in which 303 participants completed photo-elicitation interviews. We offer 8 practical suggestions for overcoming challenges encountered during photo-elicitation research and for managing ethical concerns about the use of visual data in public health research. Our guidelines can inform study design, protocol development, and institutional review board approval. PMID:25357257

Examining of Model Eliciting Activities Developed by Mathematics Student Teachers

ERIC Educational Resources Information Center

Dede, Ayse Tekin; Hidiroglu, Çaglar Naci; Güzel, Esra Bukova

2017-01-01

The purpose of this study is to examine the model eliciting activities developed by the mathematics student teachers in the context of the principles of the model eliciting activities. The participants of the study conducted as a case study design were twenty one mathematics student teachers working on seven groups. The data collection tools were…

Allatotropin: A pleiotropic neuropeptide that elicits mosquito immune responses

PubMed Central

Sánchez-Zavaleta, Minerva; Brito, Kevin; Herrera-Ortiz, Antonia; Ons, Sheila; Noriega, Fernando G.

2017-01-01

Allatotropins (AT) are neuropeptides with pleotropic functions on a variety of insect tissues. They affect processes such as juvenile hormone biosynthesis, cardiac rhythm, oviduct and hindgut contractions, nutrient absorption and circadian cycle. The present work provides experimental evidence that AT elicits immune responses in two important mosquito disease vectors, Anopheles albimanus and Aedes aegypti. Hemocytes and an immune-competent mosquito cell line responded to AT by showing strong morphological changes and increasing bacterial phagocytic activity. Phenoloxidase activity in hemolymph was also increased in Ae. aegypti mosquitoes treated with AT but not in An. albimanus, suggesting differences in the AT-dependent immune activation in the two species. In addition, two important insect immune markers, nitric oxide levels and expression of antimicrobial peptide genes, were increased in An. albimanus guts after AT treatment. AT conjugated to quantum dot nanocrystals (QDots) specifically labeled hemocytes in vivo in both mosquito species, implying molecular interactions between AT and hemocytes. The results of our studies suggest a new role for AT in the modulation of the immune response in mosquitoes. PMID:28426765

Allatotropin: A pleiotropic neuropeptide that elicits mosquito immune responses.

PubMed

Hernández-Martínez, Salvador; Sánchez-Zavaleta, Minerva; Brito, Kevin; Herrera-Ortiz, Antonia; Ons, Sheila; Noriega, Fernando G

2017-01-01

Allatotropins (AT) are neuropeptides with pleotropic functions on a variety of insect tissues. They affect processes such as juvenile hormone biosynthesis, cardiac rhythm, oviduct and hindgut contractions, nutrient absorption and circadian cycle. The present work provides experimental evidence that AT elicits immune responses in two important mosquito disease vectors, Anopheles albimanus and Aedes aegypti. Hemocytes and an immune-competent mosquito cell line responded to AT by showing strong morphological changes and increasing bacterial phagocytic activity. Phenoloxidase activity in hemolymph was also increased in Ae. aegypti mosquitoes treated with AT but not in An. albimanus, suggesting differences in the AT-dependent immune activation in the two species. In addition, two important insect immune markers, nitric oxide levels and expression of antimicrobial peptide genes, were increased in An. albimanus guts after AT treatment. AT conjugated to quantum dot nanocrystals (QDots) specifically labeled hemocytes in vivo in both mosquito species, implying molecular interactions between AT and hemocytes. The results of our studies suggest a new role for AT in the modulation of the immune response in mosquitoes.

Genome-wide gene expression effects in B6C3F1 mouse intestinal epithelia following 7 and 90days of exposure to hexavalent chromium in drinking water.

PubMed

Kopec, Anna K; Kim, Suntae; Forgacs, Agnes L; Zacharewski, Timothy R; Proctor, Deborah M; Harris, Mark A; Haws, Laurie C; Thompson, Chad M

2012-02-15

Chronic administration of high doses of hexavalent chromium [Cr(VI)] as sodium dichromate dihydrate (SDD) elicits alimentary cancers in mice. To further elucidate key events underlying tumor formation, a 90-day drinking water study was conducted in B6C3F1 mice. Differential gene expression was examined in duodenal and jejunal epithelial samples following 7 or 90days of exposure to 0, 0.3, 4, 14, 60, 170 or 520mg/L SDD in drinking water. Genome-wide microarray analyses identified 6562 duodenal and 4448 jejunal unique differentially expressed genes at day 8, and 4630 and 4845 unique changes, respectively, in the duodenum and jejunum at day 91. Comparative analysis identified significant overlap in duodenal and jejunal differential gene expression. Automated dose-response modeling identified >80% of the differentially expressed genes exhibited sigmoidal dose-response curves with EC(50) values ranging from 10 to 100mg/L SDD. Only 16 genes satisfying the dose-dependent differential expression criteria had EC(50) values <10mg/L SDD, 3 of which were regulated by Nrf2, suggesting oxidative stress in response to SDD at low concentrations. Analyses of differentially expressed genes identified over-represented functions associated with oxidative stress, cell cycle, lipid metabolism, and immune responses consistent with the reported effects on redox status and histopathology at corresponding SDD drinking water concentrations. Collectively, these data are consistent with a mode of action involving oxidative stress and cytotoxicity as early key events. This suggests that the tumorigenic effects of chronic Cr(VI) oral exposure likely require chronic tissue damage and compensatory epithelial cell proliferation. Copyright © 2011 Elsevier Inc. All rights reserved.

Gene therapy oversight: lessons for nanobiotechnology.

PubMed

Wolf, Susan M; Gupta, Rishi; Kohlhepp, Peter

2009-01-01

Oversight of human gene transfer research ("gene therapy") presents an important model with potential application to oversight of nanobiology research on human participants. Gene therapy oversight adds centralized federal review at the National Institutes of Health's Office of Biotechnology Activities and its Recombinant DNA Advisory Committee to standard oversight of human subjects research at the researcher's institution (by the Institutional Review Board and, for some research, the Institutional Biosafety Committee) and at the federal level by the Office for Human Research Protections. The Food and Drug Administration's Center for Biologics Evaluation and Research oversees human gene transfer research in parallel, including approval of protocols and regulation of products. This article traces the evolution of this dual oversight system; describes how the system is already addressing nanobiotechnology in gene transfer: evaluates gene therapy oversight based on public opinion, the literature, and preliminary expert elicitation; and offers lessons of the gene therapy oversight experience for oversight of nanobiotechnology.

Exposure to 2.45 GHz electromagnetic fields elicits an HSP-related stress response in rat hippocampus.

PubMed

Yang, Xue-Sen; He, Gen-Lin; Hao, Yu-Tong; Xiao, Yang; Chen, Chun-Hai; Zhang, Guang-Bin; Yu, Zheng-Ping

2012-07-01

The issue of possible neurobiological effects of the electromagnetic field (EMF) exposure is highly controversial. To determine whether electromagnetic field exposure could act as an environmental stimulus capable of producing stress responses, we employed the hippocampus, a sensitive target of electromagnetic radiation, to assess the changes in its stress-related gene and protein expression after EMF exposure. Adult male Sprague-Dawley rats with body restrained were exposed to a 2.45 GHz EMF at a specific absorption rate (SAR) of 6 W/kg or sham conditions. cDNA microarray was performed to examine the changes of gene expression involved in the biological effects of electromagnetic radiation. Of 2048 candidate genes, 23 upregulated and 18 downregulated genes were identified. Of these differential expression genes, two heat shock proteins (HSP), HSP27 and HSP70, are notable because expression levels of both proteins are increased in the rat hippocampus. Result from immunocytochemistry revealed that EMF caused intensive staining for HSP27 and HSP70 in the hippocampus, especially in the pyramidal neurons of cornu ammonis 3 (CA3) and granular cells of dentate gyrus (DG). The gene and protein expression profiles of HSP27 and HSP70 were further confirmed by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Our data provide direct evidence that exposure to electromagnetic fields elicits a stress response in the rat hippocampus. Copyright © 2012 Elsevier Inc. All rights reserved.

Novel groups and unique distribution of phage phoH genes in paddy waters in northeast China

PubMed Central

Wang, Xinzhen; Liu, Junjie; Yu, Zhenhua; Jin, Jian; Liu, Xiaobing; Wang, Guanghua

2016-01-01

Although bacteriophages are ubiquitous in various environments, their genetic diversity is primarily investigated in pelagic marine environments. Corresponding studies in terrestrial environments are few. In this study, we conducted the first survey of phage diversity in the paddy ecosystem by targeting a new viral biomarker gene, phoH. A total of 424 phoH sequences were obtained from four paddy waters generated from a pot experiment with different soils collected from open paddy fields in northeast China. The majority of phoH sequences in paddy waters were novel, with the highest identity of ≤70% with known phoH sequences. Four unique groups (Group α, Group β, Group γ and Group δ) and seven new subgroups (Group 2b, Group 3d, Group 3e, Group 6a, Group 6b, Group 6c and Group 6d) were formed exclusively with the clones from the paddy waters, suggesting novel phage phoH groups exist in the paddy ecosystem. Additionally, the distribution proportions of phoH clones in different groups varied among paddy water samples, suggesting the phage community in paddy fields is biogeographically distributed. Furthermore, non-metric multidimensional scaling analysis indicated that phage phoH assemblages in paddy waters were distinct from those in marine waters. PMID:27910929

Sub-lethal levels of electric current elicit the biosynthesis of plant secondary metabolites.

PubMed

Kaimoyo, Evans; Farag, Mohamed A; Sumner, Lloyd W; Wasmann, Catherine; Cuello, Joel L; VanEtten, Hans

2008-01-01

Many secondary metabolites that are normally undetectable or in low amounts in healthy plant tissue are synthesized in high amounts in response to microbial infection. Various abiotic and biotic agents have been shown to mimic microorganisms and act as elicitors of the synthesis of these plant compounds. In the present study, sub-lethal levels of electric current are shown to elicit the biosynthesis of secondary metabolites in transgenic and non-transgenic plant tissue. The production of the phytoalexin (+)-pisatin by pea was used as the main model system. Non-transgenic pea hairy roots treated with 30-100 mA of electric current produced 13 times higher amounts of (+)-pisatin than did the non-elicited controls. Electrically elicited transgenic pea hairy root cultures blocked at various enzymatic steps in the (+)-pisatin biosynthetic pathway also accumulated intermediates preceding the blocked enzymatic step. Secondary metabolites not usually produced by pea accumulated in some of the transgenic root cultures after electric elicitation due to the diversion of the intermediates into new pathways. The amount of pisatin in the medium bathing the roots of electro-elicited roots of hydroponically cultivated pea plants was 10 times higher 24 h after elicitation than in the medium surrounding the roots of non-elicited control plants, showing not only that the electric current elicited (+)-pisatin biosynthesis but also that the (+)-pisatin was released from the roots. Seedlings, intact roots or cell suspension cultures of fenugreek (Trigonella foenum-graecum), barrel medic, (Medicago truncatula), Arabidopsis thaliana, red clover (Trifolium pratense) and chickpea (Cicer arietinum) also produced increased levels of secondary metabolites in response to electro-elicitation. On the basis of our results, electric current would appear to be a general elicitor of plant secondary metabolites and to have potential for application in both basic and commercial research.

Sample Size for Measuring Grammaticality in Preschool Children from Picture-Elicited Language Samples

ERIC Educational Resources Information Center

Eisenberg, Sarita L.; Guo, Ling-Yu

2015-01-01

Purpose: The purpose of this study was to investigate whether a shorter language sample elicited with fewer pictures (i.e., 7) would yield a percent grammatical utterances (PGU) score similar to that computed from a longer language sample elicited with 15 pictures for 3-year-old children. Method: Language samples were elicited by asking forty…

Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis

PubMed Central

Blanchard, Carine; Wang, Ning; Stringer, Keith F.; Mishra, Anil; Fulkerson, Patricia C.; Abonia, J. Pablo; Jameson, Sean C.; Kirby, Cassie; Konikoff, Michael R.; Collins, Margaret H.; Cohen, Mitchell B.; Akers, Rachel; Hogan, Simon P.; Assa’ad, Amal H.; Putnam, Philip E.; Aronow, Bruce J.; Rothenberg, Marc E.

2006-01-01

Eosinophilic esophagitis (EE) is an emerging disorder with a poorly understood pathogenesis. In order to define disease mechanisms, we took an empirical approach analyzing esophageal tissue by a genome-wide microarray expression analysis. EE patients had a striking transcript signature involving 1% of the human genome that was remarkably conserved across sex, age, and allergic status and was distinct from that associated with non-EE chronic esophagitis. Notably, the gene encoding the eosinophil-specific chemoattractant eotaxin-3 (also known as CCL26) was the most highly induced gene in EE patients compared with its expression level in healthy individuals. Esophageal eotaxin-3 mRNA and protein levels strongly correlated with tissue eosinophilia and mastocytosis. Furthermore, a single-nucleotide polymorphism in the human eotaxin-3 gene was associated with disease susceptibility. Finally, mice deficient in the eotaxin receptor (also known as CCR3) were protected from experimental EE. These results implicate eotaxin-3 as a critical effector molecule for EE and provide insight into disease pathogenesis. PMID:16453027

Stimulus ambiguity elicits response conflict.

PubMed

Szmalec, Arnaud; Verbruggen, Frederick; Vandierendonck, André; De Baene, Wouter; Verguts, Tom; Notebaert, Wim

2008-04-18

Conflict monitoring theory [M.M. Botvinick, T. Braver, D. Barch, C. Carter, J.D. Cohen, Conflict monitoring and cognitive control, Psychol. Rev. 108 (2001) 625-652] assumes that perceptual ambiguity among choice stimuli elicits response conflict in choice reaction. It hence predicts that response conflict is also involved in elementary variants of choice reaction time (RT) tasks, i.e., those variants that, by contrast with the Stroop task or the Go/No-Go task for instance, are rarely associated with cognitive control. In order to test this prediction, an experiment was designed in which participants performed a simple RT task and a regular between-hand 2-choice RT task under three different levels of stimulus ambiguity. The data show that response conflict, as measured by the N2 component of the event-related brain potential (ERP), was elicited in the 2-choice RT task but not in the simple RT task and that the degree of response conflict in the 2-choice RT task was a function of stimulus ambiguity. These results show that response conflict is also present in a regular choice RT task which is traditionally not considered to be a measure of cognitive conflict.

Pattern Visual Evoked Potentials Elicited by Organic Electroluminescence Screen

PubMed Central

Matsumoto, Celso Soiti; Shinoda, Kei; Matsumoto, Harue; Funada, Hideaki; Minoda, Haruka

2014-01-01

Purpose. To determine whether organic electroluminescence (OLED) screens can be used as visual stimulators to elicit pattern-reversal visual evoked potentials (p-VEPs). Method. Checkerboard patterns were generated on a conventional cathode-ray tube (S710, Compaq Computer Co., USA) screen and on an OLED (17 inches, 320 × 230 mm, PVM-1741, Sony, Tokyo, Japan) screen. The time course of the luminance changes of each monitor was measured with a photodiode. The p-VEPs elicited by these two screens were recorded from 15 eyes of 9 healthy volunteers (22.0 ± 0.8 years). Results. The OLED screen had a constant time delay from the onset of the trigger signal to the start of the luminescence change. The delay during the reversal phase from black to white for the pattern was 1.0 msec on the cathode-ray tube (CRT) screen and 0.5 msec on the OLED screen. No significant differences in the amplitudes of P100 and the implicit times of N75 and P100 were observed in the p-VEPs elicited by the CRT and the OLED screens. Conclusion. The OLED screen can be used as a visual stimulator to elicit p-VEPs; however the time delay and the specific properties in the luminance change must be taken into account. PMID:25197652

Conserved small mRNA with an unique, extended Shine-Dalgarno sequence

PubMed Central

Hahn, Julia; Migur, Anzhela; von Boeselager, Raphael Freiherr; Kubatova, Nina; Kubareva, Elena; Schwalbe, Harald

2017-01-01

ABSTRACT Up to now, very small protein-coding genes have remained unrecognized in sequenced genomes. We identified an mRNA of 165 nucleotides (nt), which is conserved in Bradyrhizobiaceae and encodes a polypeptide with 14 amino acid residues (aa). The small mRNA harboring a unique Shine-Dalgarno sequence (SD) with a length of 17 nt was localized predominantly in the ribosome-containing P100 fraction of Bradyrhizobium japonicum USDA 110. Strong interaction between the mRNA and 30S ribosomal subunits was demonstrated by their co-sedimentation in sucrose density gradient. Using translational fusions with egfp, we detected weak translation and found that it is impeded by both the extended SD and the GTG start codon (instead of ATG). Biophysical characterization (CD- and NMR-spectroscopy) showed that synthesized polypeptide remained unstructured in physiological puffer. Replacement of the start codon by a stop codon increased the stability of the transcript, strongly suggesting additional posttranscriptional regulation at the ribosome. Therefore, the small gene was named rreB (ribosome-regulated expression in Bradyrhizobiaceae). Assuming that the unique ribosome binding site (RBS) is a hallmark of rreB homologs or similarly regulated genes, we looked for similar putative RBS in bacterial genomes and detected regions with at least 16 nt complementarity to the 3′-end of 16S rRNA upstream of sORFs in Caulobacterales, Rhizobiales, Rhodobacterales and Rhodospirillales. In the Rhodobacter/Roseobacter lineage of α-proteobacteria the corresponding gene (rreR) is conserved and encodes an 18 aa protein. This shows how specific RBS features can be used to identify new genes with presumably similar control of expression at the RNA level. PMID:27834614

Gene Expression Analysis of Early Stage Endometrial Cancers Reveals Unique Transcripts Associated with Grade and Histology but Not Depth of Invasion

PubMed Central

Risinger, John I.; Allard, Jay; Chandran, Uma; Day, Roger; Chandramouli, Gadisetti V. R.; Miller, Caela; Zahn, Christopher; Oliver, Julie; Litzi, Tracy; Marcus, Charlotte; Dubil, Elizabeth; Byrd, Kevin; Cassablanca, Yovanni; Becich, Michael; Berchuck, Andrew; Darcy, Kathleen M.; Hamilton, Chad A.; Conrads, Thomas P.; Maxwell, G. Larry

2013-01-01

Endometrial cancer is the most common gynecologic malignancy in the United States but it remains poorly understood at the molecular level. This investigation was conducted to specifically assess whether gene expression changes underlie the clinical and pathologic factors traditionally used for determining treatment regimens in women with stage I endometrial cancer. These include the effect of tumor grade, depth of myometrial invasion and histotype. We utilized oligonucleotide microarrays to assess the transcript expression profile in epithelial glandular cells laser microdissected from 79 endometrioid and 12 serous stage I endometrial cancers with a heterogeneous distribution of grade and depth of myometrial invasion, along with 12 normal post-menopausal endometrial samples. Unsupervised multidimensional scaling analyses revealed that serous and endometrioid stage I cancers have similar transcript expression patterns when compared to normal controls where 900 transcripts were identified to be differentially expressed by at least fourfold (univariate t-test, p < 0.001) between the cancers and normal endometrium. This analysis also identified transcript expression differences between serous and endometrioid cancers and tumor grade, but no apparent differences were identified as a function of depth of myometrial invasion. Four genes were validated by quantitative PCR on an independent set of cancer and normal endometrium samples. These findings indicate that unique gene expression profiles are associated with histologic type and grade, but not myometrial invasion among early stage endometrial cancers. These data provide a comprehensive perspective on the molecular alterations associated with stage I endometrial cancer, particularly those subtypes that have the worst prognosis. PMID:23785665

Gene expression analysis of rocket salad under pre-harvest and postharvest stresses: A transcriptomic resource for Diplotaxis tenuifolia

PubMed Central

Cavaiuolo, Marina; Cocetta, Giacomo; Spadafora, Natasha Damiana; Müller, Carsten T.; Rogers, Hilary J.

2017-01-01

Diplotaxis tenuifolia L. is of important economic value in the fresh-cut industry for its nutraceutical and sensorial properties. However, information on the molecular mechanisms conferring tolerance of harvested leaves to pre- and postharvest stresses during processing and shelf-life have never been investigated. Here, we provide the first transcriptomic resource of rocket by de novo RNA sequencing assembly, functional annotation and stress-induced expression analysis of 33874 transcripts. Transcriptomic changes in leaves subjected to commercially-relevant pre-harvest (salinity, heat and nitrogen starvation) and postharvest stresses (cold, dehydration, dark, wounding) known to affect quality and shelf-life were analysed 24h after stress treatment, a timing relevant to subsequent processing of salad leaves. Transcription factors and genes involved in plant growth regulator signaling, autophagy, senescence and glucosinolate metabolism were the most affected by the stresses. Hundreds of genes with unknown function but uniquely expressed under stress were identified, providing candidates to investigate stress responses in rocket. Dehydration and wounding had the greatest effect on the transcriptome and different stresses elicited changes in the expression of genes related to overlapping groups of hormones. These data will allow development of approaches targeted at improving stress tolerance, quality and shelf-life of rocket with direct applications in the fresh-cut industries. PMID:28558066

Gene expression analysis of rocket salad under pre-harvest and postharvest stresses: A transcriptomic resource for Diplotaxis tenuifolia.

PubMed

Cavaiuolo, Marina; Cocetta, Giacomo; Spadafora, Natasha Damiana; Müller, Carsten T; Rogers, Hilary J; Ferrante, Antonio

2017-01-01

Diplotaxis tenuifolia L. is of important economic value in the fresh-cut industry for its nutraceutical and sensorial properties. However, information on the molecular mechanisms conferring tolerance of harvested leaves to pre- and postharvest stresses during processing and shelf-life have never been investigated. Here, we provide the first transcriptomic resource of rocket by de novo RNA sequencing assembly, functional annotation and stress-induced expression analysis of 33874 transcripts. Transcriptomic changes in leaves subjected to commercially-relevant pre-harvest (salinity, heat and nitrogen starvation) and postharvest stresses (cold, dehydration, dark, wounding) known to affect quality and shelf-life were analysed 24h after stress treatment, a timing relevant to subsequent processing of salad leaves. Transcription factors and genes involved in plant growth regulator signaling, autophagy, senescence and glucosinolate metabolism were the most affected by the stresses. Hundreds of genes with unknown function but uniquely expressed under stress were identified, providing candidates to investigate stress responses in rocket. Dehydration and wounding had the greatest effect on the transcriptome and different stresses elicited changes in the expression of genes related to overlapping groups of hormones. These data will allow development of approaches targeted at improving stress tolerance, quality and shelf-life of rocket with direct applications in the fresh-cut industries.

Eliciting User Requirements Using Appreciative Inquiry

ERIC Educational Resources Information Center

Gonzales, Carol Kernitzki

2010-01-01

Many software development projects fail because they do not meet the needs of users, are over-budget, and abandoned. To address this problem, the user requirements elicitation process was modified based on principles of Appreciative Inquiry. Appreciative Inquiry, commonly used in organizational development, aims to build organizations, processes,…

Eliciting Proto-Imperatives and Proto-Declaratives in Children with Intellectual Disabilities

ERIC Educational Resources Information Center

Vandereet, Joke; Maes, Bea; Lembrechts, Dirk; Zink, Inge

2010-01-01

Background: Although high-structured elicitation tasks have been shown to be efficient means to sample communication in children with intellectual disabilities, their validity and reliability remain to be evaluated. The aims of this study were threefold: (i) to evaluate the eliciting potential, (ii) to examine the utterance forms of…

Methods to elicit probability distributions from experts: a systematic review of reported practice in health technology assessment.

PubMed

Grigore, Bogdan; Peters, Jaime; Hyde, Christopher; Stein, Ken

2013-11-01

Elicitation is a technique that can be used to obtain probability distribution from experts about unknown quantities. We conducted a methodology review of reports where probability distributions had been elicited from experts to be used in model-based health technology assessments. Databases including MEDLINE, EMBASE and the CRD database were searched from inception to April 2013. Reference lists were checked and citation mapping was also used. Studies describing their approach to the elicitation of probability distributions were included. Data was abstracted on pre-defined aspects of the elicitation technique. Reports were critically appraised on their consideration of the validity, reliability and feasibility of the elicitation exercise. Fourteen articles were included. Across these studies, the most marked features were heterogeneity in elicitation approach and failure to report key aspects of the elicitation method. The most frequently used approaches to elicitation were the histogram technique and the bisection method. Only three papers explicitly considered the validity, reliability and feasibility of the elicitation exercises. Judged by the studies identified in the review, reports of expert elicitation are insufficient in detail and this impacts on the perceived usability of expert-elicited probability distributions. In this context, the wider credibility of elicitation will only be improved by better reporting and greater standardisation of approach. Until then, the advantage of eliciting probability distributions from experts may be lost.

South African Papilionoid Legumes Are Nodulated by Diverse Burkholderia with Unique Nodulation and Nitrogen-Fixation Loci

PubMed Central

Beukes, Chrizelle W.; Venter, Stephanus N.; Law, Ian J.; Phalane, Francina L.; Steenkamp, Emma T.

2013-01-01

The root-nodule bacteria of legumes endemic to the Cape Floristic Region are largely understudied, even though recent reports suggest the occurrence of nodulating Burkholderia species unique to the region. In this study, we considered the diversity and evolution of nodulating Burkholderia associated with the endemic papilionoid tribes Hypocalypteae and Podalyrieae. We identified distinct groups from verified rhizobial isolates by phylogenetic analyses of the 16S rRNA and recA housekeeping gene regions. In order to gain insight into the evolution of the nodulation and diazotrophy of these rhizobia we analysed the genes encoding NifH and NodA. The majority of these 69 isolates appeared to be unique, potentially representing novel species. Evidence of horizontal gene transfer determining the symbiotic ability of these Cape Floristic Region isolates indicate evolutionary origins distinct from those of nodulating Burkholderia from elsewhere in the world. Overall, our findings suggest that Burkholderia species associated with fynbos legumes are highly diverse and their symbiotic abilities have unique ancestries. It is therefore possible that the evolution of these bacteria is closely linked to the diversification and establishment of legumes characteristic of the Cape Floristic Region. PMID:23874611

Whole-Genome Phylogenetic Analysis of Influenza B/Phuket/3073/2013-Like Viruses and Unique Reassortants Detected in Malaysia between 2012 and 2014

PubMed Central

Tan, Joon Ling; Chan, Kok Gan; Kamarulzaman, Adeeba; Chan, Yoke Fun; Sam, I-Ching; Tee, Kok Keng

2017-01-01

Reassortment of genetic segments between and within influenza B lineages (Victoria and Yamagata) has been shown to generate novel reassortants with unique genetic characteristics. Based on hemagglutinin (HA) and neuraminidase (NA) genes, recent surveillance study has identified reassortment properties in B/Phuket/3073/2013-like virus, which is currently used in the WHO-recommended influenza vaccine. To understand the potential reassortment patterns for all gene segments, four B/Phuket/3073/2013-like viruses and two unique reassortants (one each from Yamagata and Victoria) detected in Malaysia from 2012–2014 were subjected to whole-genome sequencing. Each gene was phylogenetically classified into lineages, clades and sub-clades. Three B/Phuket/3073/2013-like viruses from Yamagata lineage were found to be intra-clade reassortants, possessing PA and NA genes derived from Stockholm/12-like sub-clade, while the remaining genes from Wisconsin/01-like sub-clade (both sub-clades were within Yamagata Clade 3/Yam-3). However, the other B/Phuket/3073/2013-like virus had NS gene that derived from Stockholm/12-like sub-clade instead of Wisconsin/01-like sub-clade. One inter-clade reassortant had Yamagata Clade 2/Yam-2-derived HA and NP, and its remaining genes were Yam-3-derived. Within Victoria Clade 1/Vic-1 in Victoria lineage, one virus had intra-clade reassortment properties: HA and PB2 from Vic-1B sub-clade, MP and NS from a unique sub-clade “Vic-1C”, and the remaining genes from Vic-1A sub-clade. Although random reassortment event may generate unique reassortants, detailed phylogenetic classification of gene segments showed possible genetic linkage between PA and NA genes in B/Phuket/3073/2013-like viruses, which requires further investigation. Understanding on reassortment patterns in influenza B evolution may contribute to future vaccine design. PMID:28129386

Late Multiple Organ Surge in Interferon-Regulated Target Genes Characterizes Staphylococcal Enterotoxin B Lethality

PubMed Central

Ferreyra, Gabriela A.; Elinoff, Jason M.; Demirkale, Cumhur Y.; Starost, Matthew F.; Buckley, Marilyn; Munson, Peter J.; Krakauer, Teresa; Danner, Robert L.

2014-01-01

Background Bacterial superantigens are virulence factors that cause toxic shock syndrome. Here, the genome-wide, temporal response of mice to lethal intranasal staphylococcal enterotoxin B (SEB) challenge was investigated in six tissues. Results The earliest responses and largest number of affected genes occurred in peripheral blood mononuclear cells (PBMC), spleen, and lung tissues with the highest content of both T-cells and monocyte/macrophages, the direct cellular targets of SEB. In contrast, the response of liver, kidney, and heart was delayed and involved fewer genes, but revealed a dominant genetic program that was seen in all 6 tissues. Many of the 85 uniquely annotated transcripts participating in this shared genomic response have not been previously linked to SEB. Nine of the 85 genes were subsequently confirmed by RT-PCR in every tissue/organ at 24 h. These 85 transcripts, up-regulated in all tissues, annotated to the interferon (IFN)/antiviral-response and included genes belonging to the DNA/RNA sensing system, DNA damage repair, the immunoproteasome, and the ER/metabolic stress-response and apoptosis pathways. Overall, this shared program was identified as a type I and II interferon (IFN)-response and the promoters of these genes were highly enriched for IFN regulatory matrices. Several genes whose secreted products induce the IFN pathway were up-regulated at early time points in PBMCs, spleen, and/or lung. Furthermore, IFN regulatory factors including Irf1, Irf7 and Irf8, and Zbp1, a DNA sensor/transcription factor that can directly elicit an IFN innate immune response, participated in this host-wide SEB signature. Conclusion Global gene-expression changes across multiple organs implicated a host-wide IFN-response in SEB-induced death. Therapies aimed at IFN-associated innate immunity may improve outcome in toxic shock syndromes. PMID:24551153

Comparative analysis of TCDD-induced AhR-mediated gene expression in human, mouse and rat primary B cells

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

Kovalova, Natalia, E-mail: kovalova@msu.edu

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant that activates the aryl hydrocarbon receptor (AhR) resulting in altered gene expression. In vivo, in vitro, and ex vivo studies have demonstrated that B cells are directly impaired by TCDD, and are a sensitive target as evidenced by suppression of antibody responses. The window of sensitivity to TCDD-induced suppression of IgM secretion among mouse, rat and human B cells is similar. Specifically, TCDD must be present within the initial 12 h post B cell stimulation, indicating that TCDD disrupts early signaling network(s) necessary for B lymphocyte activation and differentiation. Therefore, we hypothesized thatmore » TCDD treatment across three different species (mouse, rat and human) triggers a conserved, B cell-specific mechanism that is involved in TCDD-induced immunosuppression. RNA sequencing (RNA-Seq) was used to identify B cell-specific orthologous genes that are differentially expressed in response to TCDD in primary mouse, rat and human B cells. Time course studies identified TCDD-elicited differential expression of 515 human, 2371 mouse and 712 rat orthologous genes over the 24-h period. 28 orthologs were differentially expressed in response to TCDD in all three species. Overrepresented pathways enriched in all three species included cytokine-cytokine receptor interaction, ECM-receptor interaction, focal adhesion, regulation of actin cytoskeleton and pathways in cancer. Differentially expressed genes functionally associated with cell-cell signaling in humans, immune response in mice, and oxidation reduction in rats. Overall, these results suggest that despite the conservation of the AhR and its signaling mechanism, TCDD elicits species-specific gene expression changes. - Highlights: • Kovalova TAAP Highlights Nov. 2016 • RNA-Seq identified TCDD-induced gene expression in PWM-activated primary B cells. • TCDD elicited differential expression of 515 human, 2371 mouse

Explaining human uniqueness: genome interactions with environment, behaviour and culture.

PubMed

Varki, Ajit; Geschwind, Daniel H; Eichler, Evan E

2008-10-01

What makes us human? Specialists in each discipline respond through the lens of their own expertise. In fact, 'anthropogeny' (explaining the origin of humans) requires a transdisciplinary approach that eschews such barriers. Here we take a genomic and genetic perspective towards molecular variation, explore systems analysis of gene expression and discuss an organ-systems approach. Rejecting any 'genes versus environment' dichotomy, we then consider genome interactions with environment, behaviour and culture, finally speculating that aspects of human uniqueness arose because of a primate evolutionary trend towards increasing and irreversible dependence on learned behaviours and culture - perhaps relaxing allowable thresholds for large-scale genomic diversity.

Explaining human uniqueness: genome interactions with environment, behaviour and culture

PubMed Central

Varki, Ajit; Geschwind, Daniel H.; Eichler, Evan E.

2009-01-01

What makes us human? Specialists in each discipline respond through the lens of their own expertise. In fact, ‘anthropogeny’ (explaining the origin of humans) requires a transdisciplinary approach that eschews such barriers. Here we take a genomic and genetic perspective towards molecular variation, explore systems analysis of gene expression and discuss an organ-systems approach. Rejecting any ‘genes versus environment’ dichotomy, we then consider genome interactions with environment, behaviour and culture, finally speculating that aspects of human uniqueness arose because of a primate evolutionary trend towards increasing and irreversible dependence on learned behaviours and culture — perhaps relaxing allowable thresholds for large-scale genomic diversity. PMID:18802414

Visualising community: using participant-driven photo-elicitation for research and application

Treesearch

Paul M. Van Auken; Svein J. Frisvoll; Susan I. Stewart

2010-01-01

Despite a contemporary socio-culture revolving around cultural consumption of imagery, metaphors, representations and "gaze", photo-elicitation is a rarely used method for social scientists and planners to acquire knowledge. In this paper, we discuss participant-driven photo-elicitation, a process in which participant photos are paired with in-depth...

Effects of penicillin on procaine-elicited bursts of potential in central neuron of snail, Achatina fulica.

PubMed

Chen, Yi-Hung; Lu, Kuan-Ling; Hsiao, Ru-Wan; Lee, Ya-Ling; Tsai, Hong-Chieh; Lin, Chia Hsien; Tsai, Ming-Cheng

2008-08-01

Effects of penicillin on changes in procaine-elicited bursts of potential (BoP) were studied in a central neuron (RP4) of snail, Achatina fulica Ferussac. Procaine elicited BoP in the RP4 neuron while penicillin elicited depolarization of the neuron. Penicillin decreased the BoP elicited by procaine in a concentration-dependent manner. The effect of penicillin on the procaine-elicited BoP was not altered in the preparations treated with ascorbate or L-NAME (N-nitro-L-arginine methyl ester). However, the inhibitory effect of penicillin on the procaine-elicited BoP was enhanced with a decrease in extracellular sodium ion. Sodium ion was one of the important ions contributing to the action potential of the neuron. Two-electrode voltage-clamp studies revealed that penicillin decreased the fast sodium inward current of the neuron. It is concluded that penicillin inhibited the BoP elicited by procaine and sodium ion altered the effect of penicillin on procaine-elicited BoP.

Salient Beliefs in Majoring in Management Information Systems: An Elicitation Study

ERIC Educational Resources Information Center

Chipidza, Wallace; Green, Gina; Riemenschneider, Cindy

2016-01-01

Research utilizing the Theory of Planned Behavior to understand behavior should first elicit beliefs about the phenomenon from the target population. In order to understand the reasons why students choose to major or not major in Management Information Systems (MIS), we elicited beliefs from 136 students attending university in the United States…

Lactofen induces isoflavone accumulation and glyceollin elicitation competency in soybean.

PubMed

Landini, Serena; Graham, Madge Y; Graham, Terrence L

2003-03-01

Lactofen, the active ingredient of the soybean disease resistance-inducing herbicide, Cobra, induces large accumulations of isoflavone conjugates and aglycones in soybean tissues. The predominant isoflavones induced in cotyledon tissues are daidzein (and its conjugates) and formononetin and glycitein aglycones. The latter two isoflavones are usually present only at very low levels in soybean seedling tissues. In leaves, the predominant lactofen-induced isoflavones are daidzein and formononetin aglycones and the malonyl-glucosyl conjugate of genistein. Isoflavone induction also occurs in cells distal to the point of treatment, but is only weakly systemic. Lactofen also induces elicitation competency, the capacity of soybean cells to accumulate the pterocarpan phytoalexin glyceollin in response to glucan elicitors from the cell wall of the pathogen Phytophthora sojae. Comparison of the activity of a series of diphenyl ether herbicides demonstrated that while all diphenyl ethers tested induced some degree of elicitation competency, only certain ones induced isoflavone accumulation in the absence of glucan elicitor. As a group the diphenyl ethers are thought to inhibit protoporhyrinogen oxidase, eventually leading to singlet oxygen generation. Another singlet oxygen generator, rose bengal, also induced elicitation competency, but little isoflavone accumulation. It is hypothesized that diphenyl ether-induced activated oxygen species mimic some aspects of hypersensitive cell death, which leads to elicitation competency in infected tissues.

DAT Genotype Modulates Brain and Behavioral Responses Elicited by Cigarette Cues

PubMed Central

Franklin, Teresa R; Lohoff, Falk W; Wang, Ze; Sciortino, Nathan; Harper, Derek; Li, Yin; Jens, Will; Cruz, Jeffrey; Kampman, Kyle; Ehrman, Ron; Berrettini, Wade; Detre, John A; O'Brien, Charles P; Childress, Anna Rose

2011-01-01

We previously demonstrated differential activation of the mesocorticolimbic reward circuitry in response to cigarette cues independent of withdrawal. Despite robust effects, we noted considerable individual variability in brain and subjective responses. As dopamine (DA) is critical for reward and its predictive signals, genetically driven variation in DA transmission may account for the observed differences. Evidence suggests that a variable number of tandem repeats (VNTRs) polymorphism in the DA transporter (DAT) SLC6A3 gene may influence DA transport. Brain and behavioral responses may be enhanced in probands carrying the 9-repeat allele. To test this hypothesis, perfusion fMR images were acquired during cue exposure in 19 smokers genotyped for the 40 bp VNTR polymorphism in the SLC6A3 gene. Contrasts between groups revealed that 9-repeat (9-repeats) had a greater response to smoking (vs nonsmoking) cues than smokers homozygous for the 10-repeat allele (10/10-repeats) bilaterally in the interconnected ventral striatal/pallidal/orbitofrontal cortex regions (VS/VP/OFC). Activity was increased in 9-repeats and decreased in 10/10-repeats in the VS/VP/OFC (p<0.001 for all analyses). Brain activity and craving was strongly correlated in 10/10-repeats in these regions and others (anterior cingulate, parahippocampal gyrus, and insula; r2 = 0.79–0.86, p<0.001 in all regions). Alternatively, there were no significant correlations between brain and behavior in 9-repeats. There were no differences in cigarette dependence, demographics, or resting baseline neural activity between groups. These results provide evidence that genetic variation in the DAT gene contributes to the neural and behavioral responses elicited by smoking cues. PMID:18704100

The affective dimension of response elicitation data: a projective measure.

PubMed

Tibon, S; Blumberg, H H

2000-03-01

In this research, the Rorschach Affective Ratio, a measure for frequency of response elicitation, was used to examine the affective dimension of response elicitation data. The purpose of this study was to apply the Rorschach Affective Ratio to an examination of the psychodynamic roots of political behavior. This measure compares the number of responses to colored cards, considered as emotional stimuli, with those revealed by the other (black and white) cards of the test. Israeli undergraduates (N = 26) completed a questionnaire composed of 20 questions about peace. Participants who were more supportive of the peace process in the Middle East were found to have a lower Affective Ratio than those who were less supportive. This result suggests that measurable affective aspects may be as important as cognitive aspects of response elicitation in understanding an individual's political attitudes.

Plant Innate Immunity Induced by Flagellin Suppresses the Hypersensitive Response in Non-Host Plants Elicited by Pseudomonas syringae pv. averrhoi

PubMed Central

Wei, Chia-Fong; Hsu, Shih-Tien; Deng, Wen-Ling; Wen, Yu-Der; Huang, Hsiou-Chen

2012-01-01

A new pathogen, Pseudomonas syringae pv. averrhoi (Pav), which causes bacterial spot disease on carambola was identified in Taiwan in 1997. Many strains of this pathovar have been isolated from different locations and several varieties of hosts. Some of these strains, such as HL1, are nonmotile and elicit a strong hypersensitive response (HR) in nonhost tobacco leaves, while other strains, such as PA5, are motile and elicit a weak HR. Based on the image from a transmission electron microscope, the results showed that HL1 is flagellum-deficient and PA5 has normal flagella. Here we cloned and analyzed the fliC gene and glycosylation island from Pav HL1 and PA5. The amino acid sequences of FliC from HL1 and PA5 are identical to P. s. pvs. tabaci (Pta), glycinea and phaseolicola and share very high similarity with other pathovars of P. syringae. In contrast to the flagellin mutant PtaΔfliC, PA5ΔfliC grows as well as wild type in the host plant, but it elicits stronger HR than wild type does in non-host plants. Furthermore, the purified Pav flagellin, but not the divergent flagellin from Agrobacterium tumefaciens, is able to impair the HR induced by PA5ΔfliC. PA5Δfgt1 possessing nonglycosylated flagella behaved as its wild type in both bacterial growth in host and HR elicitation. Flagellin was infiltrated into tobacco leaves either simultaneously with flagellum-deficient HL1 or prior to the inoculation of wild type HL1, and both treatments impaired the HR induced by HL1. Moreover, the HR elicited by PA5 and PA5ΔfliC was enhanced by the addition of cycloheximide, suggesting that the flagellin is one of the PAMPs (pathogen-associated molecular patterns) contributed to induce the PAMP-triggered immunity (PTI). Taken together, the results shown in this study reveal that flagellin in Pav is capable of suppressing HR via PTI induction during an incompatible interaction. PMID:22911741

Plant innate immunity induced by flagellin suppresses the hypersensitive response in non-host plants elicited by Pseudomonas syringae pv. averrhoi.

PubMed

Wei, Chia-Fong; Hsu, Shih-Tien; Deng, Wen-Ling; Wen, Yu-Der; Huang, Hsiou-Chen

2012-01-01

A new pathogen, Pseudomonas syringae pv. averrhoi (Pav), which causes bacterial spot disease on carambola was identified in Taiwan in 1997. Many strains of this pathovar have been isolated from different locations and several varieties of hosts. Some of these strains, such as HL1, are nonmotile and elicit a strong hypersensitive response (HR) in nonhost tobacco leaves, while other strains, such as PA5, are motile and elicit a weak HR. Based on the image from a transmission electron microscope, the results showed that HL1 is flagellum-deficient and PA5 has normal flagella. Here we cloned and analyzed the fliC gene and glycosylation island from Pav HL1 and PA5. The amino acid sequences of FliC from HL1 and PA5 are identical to P. s. pvs. tabaci (Pta), glycinea and phaseolicola and share very high similarity with other pathovars of P. syringae. In contrast to the flagellin mutant PtaΔfliC, PA5ΔfliC grows as well as wild type in the host plant, but it elicits stronger HR than wild type does in non-host plants. Furthermore, the purified Pav flagellin, but not the divergent flagellin from Agrobacterium tumefaciens, is able to impair the HR induced by PA5ΔfliC. PA5Δfgt1 possessing nonglycosylated flagella behaved as its wild type in both bacterial growth in host and HR elicitation. Flagellin was infiltrated into tobacco leaves either simultaneously with flagellum-deficient HL1 or prior to the inoculation of wild type HL1, and both treatments impaired the HR induced by HL1. Moreover, the HR elicited by PA5 and PA5ΔfliC was enhanced by the addition of cycloheximide, suggesting that the flagellin is one of the PAMPs (pathogen-associated molecular patterns) contributed to induce the PAMP-triggered immunity (PTI). Taken together, the results shown in this study reveal that flagellin in Pav is capable of suppressing HR via PTI induction during an incompatible interaction.

Spaceflight Transcriptomes: Unique Responses to a Novel Environment

PubMed Central

Paul, Anna-Lisa; Zupanska, Agata K.; Ostrow, Dejerianne T.; Zhang, Yanping; Sun, Yijun; Li, Jian-Liang; Shanker, Savita; Farmerie, William G.; Amalfitano, Claire E.

2012-01-01

Abstract The spaceflight environment presents unique challenges to terrestrial biology, including but not limited to the direct effects of gravity. As we near the end of the Space Shuttle era, there remain fundamental questions about the response and adaptation of plants to orbital spaceflight conditions. We address a key baseline question of whether gene expression changes are induced by the orbital environment, and then we ask whether undifferentiated cells, cells presumably lacking the typical gravity response mechanisms, perceive spaceflight. Arabidopsis seedlings and undifferentiated cultured Arabidopsis cells were launched in April, 2010, as part of the BRIC-16 flight experiment on STS-131. Biologically replicated DNA microarray and averaged RNA digital transcript profiling revealed several hundred genes in seedlings and cell cultures that were significantly affected by launch and spaceflight. The response was moderate in seedlings; only a few genes were induced by more than 7-fold, and the overall intrinsic expression level for most differentially expressed genes was low. In contrast, cell cultures displayed a more dramatic response, with dozens of genes showing this level of differential expression, a list comprised primarily of heat shock–related and stress-related genes. This baseline transcriptome profiling of seedlings and cultured cells confirms the fundamental hypothesis that survival of the spaceflight environment requires adaptive changes that are both governed and displayed by alterations in gene expression. The comparison of intact plants with cultures of undifferentiated cells confirms a second hypothesis: undifferentiated cells can detect spaceflight in the absence of specialized tissue or organized developmental structures known to detect gravity. Key Words: Tissue culture—Microgravity—Low Earth orbit—Space Shuttle—Microarray. Astrobiology 12, 40–56. PMID:22221117

Testing the feasibility of eliciting preferences for health states from adolescents using direct methods.

PubMed

Crump, R Trafford; Lau, Ryan; Cox, Elizabeth; Currie, Gillian; Panepinto, Julie

2018-06-22

Measuring adolescents' preferences for health states can play an important role in evaluating the delivery of pediatric healthcare. However, formal evaluation of the common direct preference elicitation methods for health states has not been done with adolescents. Therefore, the purpose of this study is to test how these methods perform in terms of their feasibility, reliability, and validity for measuring health state preferences in adolescents. This study used a web-based survey of adolescents, 18 years of age or younger, living in the United States. The survey included four health states, each comprised of six attributes. Preferences for these health states were elicited using the visual analogue scale, time trade-off, and standard gamble. The feasibility, test-retest reliability, and construct validity of each of these preference elicitation methods were tested and compared. A total of 144 participants were included in this study. Using a web-based survey format to elicit preferences for health states from adolescents was feasible. A majority of participants completed all three elicitation methods, ranked those methods as being easy, with very few requiring assistance from someone else. However, all three elicitation methods demonstrated weak test-retest reliability, with Kendall's tau-a values ranging from 0.204 to 0.402. Similarly, all three methods demonstrated poor construct validity, with 9-50% of all rankings aligning with our expectations. There were no significant differences across age groups. Using a web-based survey format to elicit preferences for health states from adolescents is feasible. However, the reliability and construct validity of the methods used to elicit these preferences when using this survey format are poor. Further research into the effects of a web-based survey approach to eliciting preferences for health states from adolescents is needed before health services researchers or pediatric clinicians widely employ these methods.

The unique C- and N-terminal sequences of Metallothionein isoform 3 mediate growth inhibition and Vectorial active transport in MCF-7 cells.

PubMed

Voels, Brent; Wang, Liping; Sens, Donald A; Garrett, Scott H; Zhang, Ke; Somji, Seema

2017-05-25

The 3rd isoform of the metallothionein (MT3) gene family has been shown to be overexpressed in most ductal breast cancers. A previous study has shown that the stable transfection of MCF-7 cells with the MT3 gene inhibits cell growth. The goal of the present study was to determine the role of the unique C-terminal and N-terminal sequences of MT3 on phenotypic properties and gene expression profiles of MCF-7 cells. MCF-7 cells were transfected with various metallothionein gene constructs which contain the insertion or the removal of the unique MT3 C- and N-terminal domains. Global gene expression analysis was performed on the MCF-7 cells containing the various constructs and the expression of the unique C- and N- terminal domains of MT3 was correlated to phenotypic properties of the cells. The results of the present study demonstrate that the C-terminal sequence of MT3, in the absence of the N-terminal sequence, induces dome formation in MCF-7 cells, which in cell cultures is the phenotypic manifestation of a cell's ability to perform vectorial active transport. Global gene expression analysis demonstrated that the increased expression of the GAGE gene family correlated with dome formation. Expression of the C-terminal domain induced GAGE gene expression, whereas the N-terminal domain inhibited GAGE gene expression and that the effect of the N-terminal domain inhibition was dominant over the C-terminal domain of MT3. Transfection with the metallothionein 1E gene increased the expression of GAGE genes. In addition, both the C- and the N-terminal sequences of the MT3 gene had growth inhibitory properties, which correlated to an increased expression of the interferon alpha-inducible protein 6. Our study shows that the C-terminal domain of MT3 confers dome formation in MCF-7 cells and the presence of this domain induces expression of the GAGE family of genes. The differential effects of MT3 and metallothionein 1E on the expression of GAGE genes suggests unique roles of

Gene-specific mechanisms direct glucocorticoid-receptor-driven repression of inflammatory response genes in macrophages

PubMed Central

Sacta, Maria A; Tharmalingam, Bowranigan; Coppo, Maddalena; Rollins, David A; Deochand, Dinesh K; Benjamin, Bradley; Yu, Li; Zhang, Bin; Hu, Xiaoyu; Li, Rong; Chinenov, Yurii

2018-01-01

The glucocorticoid receptor (GR) potently represses macrophage-elicited inflammation, however, the underlying mechanisms remain obscure. Our genome-wide analysis in mouse macrophages reveals that pro-inflammatory paused genes, activated via global negative elongation factor (NELF) dissociation and RNA Polymerase (Pol)2 release from early elongation arrest, and non-paused genes, induced by de novo Pol2 recruitment, are equally susceptible to acute glucocorticoid repression. Moreover, in both cases the dominant mechanism involves rapid GR tethering to p65 at NF-kB-binding sites. Yet, specifically at paused genes, GR activation triggers widespread promoter accumulation of NELF, with myeloid cell-specific NELF deletion conferring glucocorticoid resistance. Conversely, at non-paused genes, GR attenuates the recruitment of p300 and histone acetylation, leading to a failure to assemble BRD4 and Mediator at promoters and enhancers, ultimately blocking Pol2 initiation. Thus, GR displays no preference for a specific pro-inflammatory gene class; however, it effects repression by targeting distinct temporal events and components of transcriptional machinery. PMID:29424686

Evaluation of Antioxidant and Antibacterial Potentials of Nigella sativa L. Suspension Cultures under Elicitation.

PubMed

Chaudhry, Hera; Fatima, Nida; Ahmad, Iffat Zareen

2015-01-01

Nigella sativa L. (family Ranunculaceae) is an annual herb of immense medicinal properties because of its major active components (i.e., thymoquinone (TQ), thymohydroquinone (THQ), and thymol (THY)). Plant tissue culture techniques like elicitation, Agrobacterium mediated transformation, hairy root culture, and so on, are applied for substantial metabolite production. This study enumerates the antibacterial and antioxidant potentials of N. sativa epicotyl suspension cultures under biotic and abiotic elicitation along with concentration optimization of the elicitors for enhanced TQ and THY production. Cultures under different concentrations of pectin and manganese chloride (MnCl2) elicitation (i.e., 5 mg/L, 10 mg/L, and 15 mg/L) showed that the control, MnCl2 10 mg/L, and pectin 15 mg/L suspension extracts greatly inhibited the growth of E. coli, S. typhimurium, and S. aureus (MIC against E. coli, i.e., 2.35 ± 0.8, 2.4 ± 0.2, and 2.46 ± 0.5, resp.). Elicitation decreased SOD enzyme activity whereas CAT enzyme activity increased remarkably under MnCl2 elicitation. MnCl2 10 mg/L and pectin 15 mg/L elicitation enhanced the DPPH radical inhibition ability, but ferric scavenging activity was comparable to the control. TQ and THY were quantified by LC-MS/MS in the cultures with high bioactive properties revealing maximum content under MnCl2 10 mg/L elicitation. Therefore, MnCl2 elicitation can be undertaken on large scale for sustainable metabolite production.

Auditory modulation of wind-elicited walking behavior in the cricket Gryllus bimaculatus.

PubMed

Fukutomi, Matasaburo; Someya, Makoto; Ogawa, Hiroto

2015-12-01

Animals flexibly change their locomotion triggered by an identical stimulus depending on the environmental context and behavioral state. This indicates that additional sensory inputs in different modality from the stimulus triggering the escape response affect the neuronal circuit governing that behavior. However, how the spatio-temporal relationships between these two stimuli effect a behavioral change remains unknown. We studied this question, using crickets, which respond to a short air-puff by oriented walking activity mediated by the cercal sensory system. In addition, an acoustic stimulus, such as conspecific 'song' received by the tympanal organ, elicits a distinct oriented locomotion termed phonotaxis. In this study, we examined the cross-modal effects on wind-elicited walking when an acoustic stimulus was preceded by an air-puff and tested whether the auditory modulation depends on the coincidence of the direction of both stimuli. A preceding 10 kHz pure tone biased the wind-elicited walking in a backward direction and elevated a threshold of the wind-elicited response, whereas other movement parameters, including turn angle, reaction time, walking speed and distance were unaffected. The auditory modulations, however, did not depend on the coincidence of the stimulus directions. A preceding sound consistently altered the wind-elicited walking direction and response probability throughout the experimental sessions, meaning that the auditory modulation did not result from previous experience or associative learning. These results suggest that the cricket nervous system is able to integrate auditory and air-puff stimuli, and modulate the wind-elicited escape behavior depending on the acoustic context. © 2015. Published by The Company of Biologists Ltd.

Nonlinear Analyses of Elicited Modal, Raised, and Pressed Rabbit Phonation

PubMed Central

Awan, Shaheen N.; Novaleski, Carolyn K.; Rousseau, Bernard

2014-01-01

Objectives/Hypothesis The purpose of this study was to use nonlinear dynamic analysis methods such as phase space portraits and correlation dimension (D2) as well as descriptive spectrographic analyses to characterize acoustic signals produced during evoked rabbit phonation. Methods Seventeen New Zealand white breeder rabbits were used to perform the study. A Grass S-88 stimulator (SA Instrumentation, Encinitas, CA) and constant current isolation unit (Grass Telefactor, model PSIU6; West Warwick, RI) were used to provide electrical stimulation to laryngeal musculature, and transglottal airflow rate and stimulation current (mA) were manipulated to elicit modal, raised intensity, and pressed phonations. Central 1 second portions of the most stable portion of the acoustic waveform for modal, raised intensity, and pressed phonations were edited, and then analyzed via phase space portraits, Poincaré sections, and the estimation of the correlation dimension (D2). In an attempt to limit the effects of the highly variable and nonstationary characteristics of some of the signals being analyzed, D2 analysis was also performed on the most stable central 200 ms portion of the acoustic waveform. Descriptive analysis of each phonation was also conducted using sound spectrograms. Results Results showed that the complexity of phonation and the subsequent acoustic waveform is increased as transglottal airflow rate and degree of glottal adduction is manipulated in the evoked rabbit phonation model. In particular, phonatory complexity, as quantified via correlation dimension analyses and demonstrated via spectrographic characteristics, increases from “modal” (i.e., phonation elicited at just above the phonation threshold pressure) to raised intensity (phonation elicited by increasing transglottal airflow rate) to pressed (phonation elicited by increasing the stimulation current delivered to the larynx). Variations in a single dynamic dimension (airflow rate or adductory force

What monitor can replace the cathode-ray tube for visual stimulation to elicit multifocal electroretinograms?

PubMed

Matsumoto, Celso Soiti; Shinoda, Kei; Matsumoto, Harue; Seki, Keisuke; Nagasaka, Eiichiro; Iwata, Takeshi; Mizota, Atsushi

2014-08-05

To compare a conventional cathode-ray tube (CRT) screen to organic light-emitting diode (OLED) and liquid crystal display (LCD) screens as visual stimulators to elicit multifocal electroretinograms (mfERGs), mfERGs were recorded from seven eyes of seven healthy volunteers (21 ± 2 years). The mfERGs elicited by a conventional CRT screen (S710, Compaq Computer Co.) were compared to those elicited by a studio-grade master OLED monitor (PVM-1741, Sony, Japan) and a conventional LCD (S1721, Flexscan, Eizo Nanao Corp., Japan). The luminance changes of each monitor were measured with a photodiode. CRT, OLED, and LCD screens with a frame frequency of 60 Hz were studied. A hexagonal stimulus array with 61 stimulus elements was created on each monitor. The serial white stimuli of the OLED screen at 60 Hz did not fuse, and that of the LCD screens fused. The amplitudes of P1 and P2 of the first-order kernels of the mfERGs were not significantly different from those elicited by the CRT and OLED screens, and the P1 amplitude of the first-order kernel elicited by the LCD stimuli was significantly smaller than that elicited by the CRT in all the groups of the averaged hexagonal elements. The implicit times were approximately 10 ms longer in almost all components elicited by the LCD screen compared to those elicited by the CRT screen. The mfERGs elicited by monitors other than the CRT should be carefully interpreted, especially those elicited by LCD screens. The OLED had good performance, and we conclude that it can replace the CRT as a stimulator for mfERGs; however, a collection of normative data is recommended. © 2014 ARVO.

Unique Gene Expression and MR T2 Relaxometry Patterns Define Chronic Murine Dextran Sodium Sulphate Colitis as a Model for Connective Tissue Changes in Human Crohn’s Disease

PubMed Central

Breynaert, Christine; Dresselaers, Tom; Perrier, Clémentine; Arijs, Ingrid; Cremer, Jonathan; Van Lommel, Leentje; Van Steen, Kristel; Ferrante, Marc; Schuit, Frans; Vermeire, Séverine; Rutgeerts, Paul; Himmelreich, Uwe; Ceuppens, Jan L.; Geboes, Karel; Van Assche, Gert

2013-01-01

Introduction Chronically relapsing inflammation, tissue remodeling and fibrosis are hallmarks of inflammatory bowel diseases. The aim of this study was to investigate changes in connective tissue in a chronic murine model resulting from repeated cycles of dextran sodium sulphate (DSS) ingestion, to mimic the relapsing nature of the human disease. Materials and Methods C57BL/6 mice were exposed to DSS in drinking water for 1 week, followed by a recovery phase of 2 weeks. This cycle of exposure was repeated for up to 3 times (9 weeks in total). Colonic inflammation, fibrosis, extracellular matrix proteins and colonic gene expression were studied. In vivo MRI T 2 relaxometry was studied as a potential non-invasive imaging tool to evaluate bowel wall inflammation and fibrosis. Results Repeated cycles of DSS resulted in a relapsing and remitting disease course, which induced a chronic segmental, transmural colitis after 2 and 3 cycles of DSS with clear induction of fibrosis and remodeling of the muscular layer. Tenascin expression mirrored its expression in Crohn’s colitis. Microarray data identified a gene expression profile different in chronic colitis from that in acute colitis. Additional recovery was associated with upregulation of unique genes, in particular keratins, pointing to activation of molecular pathways for healing and repair. In vivo MRI T2 relaxometry of the colon showed a clear shift towards higher T2 values in the acute stage and a gradual regression of T2 values with increasing cycles of DSS. Conclusions Repeated cycles of DSS exposure induce fibrosis and connective tissue changes with typical features, as occurring in Crohn’s disease. Colonic gene expression analysis revealed unique expression profiles in chronic colitis compared to acute colitis and after additional recovery, pointing to potential new targets to intervene with the induction of fibrosis. In vivo T2 relaxometry is a promising non-invasive assessment of inflammation and fibrosis

Skin-transmitted pathogens and the heebie jeebies: evidence for a subclass of disgust stimuli that evoke a qualitatively unique emotional response.

PubMed

Blake, Khandis R; Yih, Jennifer; Zhao, Kun; Sung, Billy; Harmon-Jones, Cindy

2017-09-01

Skin-transmitted pathogens have threatened humans since ancient times. We investigated whether skin-transmitted pathogens were a subclass of disgust stimuli that evoked an emotional response that was related to, but distinct from, disgust and fear. We labelled this response "the heebie jeebies". In Study 1, coding of 76 participants' experiences of disgust, fear, and the heebie jeebies showed that the heebie jeebies was elicited by unique stimuli which produced skin-crawling sensations and an urge to protect the skin. In Experiment 2,350 participants' responses to skin-transmitted pathogen, fear-inducing, and disgust-inducing vignettes showed that the vignettes elicited sensations and urges which loaded onto heebie jeebies, fear, and disgust factors, respectively. Experiment 3 largely replicated findings from Experiment 2 using video stimuli (178 participants). Results are consistent with the notion that skin-transmitted pathogens are a subclass of disgust stimuli which motivate behaviours that are functionally consistent with disgust yet qualitatively distinct.

Elevated breast cancer risk in irradiated BALB/c mice associates with unique functional polymorphism of the Prkdc (DNA-dependent protein kinase catalytic subunit) gene

NASA Technical Reports Server (NTRS)

Yu, Y.; Okayasu, R.; Weil, M. M.; Silver, A.; McCarthy, M.; Zabriskie, R.; Long, S.; Cox, R.; Ullrich, R. L.

2001-01-01

Female BALB/c mice are unusually radiosensitive and more susceptible than C57BL/6 and other tested inbred mice to ionizing radiation (IR)-induced mammary tumors. This breast cancer susceptibility is correlated with elevated susceptibility for mammary cell transformation and genomic instability following irradiation. In this study, we report the identification of two BALB/c strain-specific polymorphisms in the coding region of Prkdc, the gene encoding the DNA-dependent protein kinase catalytic subunit, which is known to be involved in DNA double-stranded break repair and post-IR signal transduction. First, we identified an A --> G transition at base 11530 resulting in a Met --> Val conversion at codon 3844 (M3844V) in the phosphatidylinositol 3-kinase domain upstream of the scid mutation (Y4046X). Second, we identified a C --> T transition at base 6418 resulting in an Arg --> Cys conversion at codon 2140 (R2140C) downstream of the putative leucine zipper domain. This unique PrkdcBALB variant gene is shown to be associated with decreased DNA-dependent protein kinase catalytic subunit activity and with increased susceptibility to IR-induced genomic instability in primary mammary epithelial cells. The data provide the first evidence that naturally arising allelic variation in a mouse DNA damage response gene may associate with IR response and breast cancer risk.

Why does anatabine, but not nicotine, accumulate in jasmonate-elicited cultured tobacco BY-2 cells?

PubMed

Shoji, Tsubasa; Hashimoto, Takashi

2008-08-01

Suspension-cultured cells of Nicotiana tabacum cv. Bright Yellow-2 (BY-2) grow rapidly in a highly homogenous population and still exhibit the general behavior of plant cells, and thus are often used as model systems in several areas of plant molecular and cellular biology, including secondary metabolism. While the parental tobacco variety synthesizes nicotine as a major alkaloid, the cultured tobacco cells mainly produce a related alkaloid anatabine, instead of nicotine, when elicited with jasmonates. We report here that cultured BY-2 cells scarcely express N-methylputrescine oxidase (MPO) genes even after jasmonate elicitation. MPO is the second enzyme in the biosynthetic pathway that supplies the pyrrolidine moiety of nicotine and nornicotine, but is predicted to be dispensable for the biosynthesis of anatabine, anabasine and anatalline, which do not contain the pyrrolidine moiety. When MPO was overexpressed in tobacco BY-2 cells, nicotine synthesis was dramatically enhanced while anatabine formation was effectively suppressed. As a complementary approach, we suppressed MPO expression by RNA interference in tobacco hairy roots that normally accumulate nicotine. In the MPO-suppressed roots, the contents of anatabine, anabasine and anatalline, as well as N-methylputrescine and putrescine, markedly increased to compensate for suppressed formation of nicotine and nornicotine. These results identify the transcriptional regulation of MPO as a critical rate-limiting step that restricts nicotine formation in cultured tobacco BY-2 cells.

Gene-to-metabolite network for biosynthesis of lignans in MeJA-elicited Isatis indigotica hairy root cultures

PubMed Central

Chen, Ruibing; Li, Qing; Tan, Hexin; Chen, Junfeng; Xiao, Ying; Ma, Ruifang; Gao, Shouhong; Zerbe, Philipp; Chen, Wansheng; Zhang, Lei

2015-01-01

Root and leaf tissue of Isatis indigotica shows notable anti-viral efficacy, and are widely used as “Banlangen” and “Daqingye” in traditional Chinese medicine. The plants' pharmacological activity is attributed to phenylpropanoids, especially a group of lignan metabolites. However, the biosynthesis of lignans in I. indigotica remains opaque. This study describes the discovery and analysis of biosynthetic genes and AP2/ERF-type transcription factors involved in lignan biosynthesis in I. indigotica. MeJA treatment revealed differential expression of three genes involved in phenylpropanoid backbone biosynthesis (IiPAL, IiC4H, Ii4CL), five genes involved in lignan biosynthesis (IiCAD, IiC3H, IiCCR, IiDIR, and IiPLR), and 112 putative AP2/ERF transcription factors. In addition, four intermediates of lariciresinol biosynthesis were found to be induced. Based on these results, a canonical correlation analysis using Pearson's correlation coefficient was performed to construct gene-to-metabolite networks and identify putative key genes and rate-limiting reactions in lignan biosynthesis. Over-expression of IiC3H, identified as a key pathway gene, was used for metabolic engineering of I. indigotica hairy roots, and resulted in an increase in lariciresinol production. These findings illustrate the utility of canonical correlation analysis for the discovery and metabolic engineering of key metabolic genes in plants. PMID:26579184

Gene Architectures that Minimize Cost of Gene Expression.

PubMed

Frumkin, Idan; Schirman, Dvir; Rotman, Aviv; Li, Fangfei; Zahavi, Liron; Mordret, Ernest; Asraf, Omer; Wu, Song; Levy, Sasha F; Pilpel, Yitzhak

2017-01-05

Gene expression burdens cells by consuming resources and energy. While numerous studies have investigated regulation of expression level, little is known about gene design elements that govern expression costs. Here, we ask how cells minimize production costs while maintaining a given protein expression level and whether there are gene architectures that optimize this process. We measured fitness of ∼14,000 E. coli strains, each expressing a reporter gene with a unique 5' architecture. By comparing cost-effective and ineffective architectures, we found that cost per protein molecule could be minimized by lowering transcription levels, regulating translation speeds, and utilizing amino acids that are cheap to synthesize and that are less hydrophobic. We then examined natural E. coli genes and found that highly expressed genes have evolved more forcefully to minimize costs associated with their expression. Our study thus elucidates gene design elements that improve the economy of protein expression in natural and heterologous systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Real-Time Elicitation of Moral Emotions Using a Prejudice Paradigm

PubMed Central

Fourie, Melike M.; Kilchenmann, Nadine; Malcolm-Smith, Susan; Thomas, Kevin G. F. 

2012-01-01

Moral emotions are critically important in guiding appropriate social conduct. Empirical investigation of these emotions remains a challenge, however, because of the difficulty in eliciting them reliably in controlled settings. Here we describe a novel prejudice paradigm that aimed to elicit both negatively and positively valenced moral emotions in real-time. Low-prejudice females (N = 46) who met highly specific demographic and personality-based screening criteria completed a series of Implicit Association Tests (IATs). Feedback following these IATs was pre-programmed to either endorse participants’ non-prejudiced self-standards (positive condition), or to contradict their self-standards (negative condition), in response to sensitive social topics. Neutral condition IATs reflected participants’ attitudes toward non-sensitive social topics. Results demonstrated that the IATs were successful in eliciting moral-positive emotions (satisfaction and pride) and moral-negative emotions (primarily guilt). In addition, participants high in self-reported punishment sensitivity, as assessed by the Behavioral Inhibition System (BIS) scale, reported greater guilt. PMID:22888322

Real-time elicitation of moral emotions using a prejudice paradigm.

PubMed

Fourie, Melike M; Kilchenmann, Nadine; Malcolm-Smith, Susan; Thomas, Kevin G F

2012-01-01

Moral emotions are critically important in guiding appropriate social conduct. Empirical investigation of these emotions remains a challenge, however, because of the difficulty in eliciting them reliably in controlled settings. Here we describe a novel prejudice paradigm that aimed to elicit both negatively and positively valenced moral emotions in real-time. Low-prejudice females (N = 46) who met highly specific demographic and personality-based screening criteria completed a series of Implicit Association Tests (IATs). Feedback following these IATs was pre-programmed to either endorse participants' non-prejudiced self-standards (positive condition), or to contradict their self-standards (negative condition), in response to sensitive social topics. Neutral condition IATs reflected participants' attitudes toward non-sensitive social topics. Results demonstrated that the IATs were successful in eliciting moral-positive emotions (satisfaction and pride) and moral-negative emotions (primarily guilt). In addition, participants high in self-reported punishment sensitivity, as assessed by the Behavioral Inhibition System (BIS) scale, reported greater guilt.

Patient Health Goals Elicited During Home Care Admission: A Categorization.

PubMed

Sockolow, Paulina; Radhakrishnan, Kavita; Chou, Edgar Y; Wojciechowicz, Christine

2017-11-01

Home care agencies are initiating "patient health goal elicitation" activities as part of home care admission planning. We categorized elicited goals and identified "clinically informative" goals at a home care agency. We examined patient goals that admitting clinicians documented in the point-of-care electronic health record; conducted content analysis on patient goal data to develop a coding scheme; grouped goal themes into codes; assigned codes to each goal; and identified goals that were in the patient voice. Of the 1,763 patient records, 16% lacked a goal; only 15 goals were in a patient's voice. Nurse and physician experts identified 12 of the 20 codes as clinically important accounting for 82% of goal occurrences. The most frequent goal documented was safety/falls (23%). Training and consistent communication of the intent and operationalization of patient goal elicitation may address the absence of patient voice and the less than universal recording of home care patients' goals.

Uncovering Pre-Service Teacher Beliefs about Young Children: A Photographic Elicitation Methodology

ERIC Educational Resources Information Center

Stockall, Nancy; Davis, Sara

2011-01-01

This illustrative paper provides an introduction to using mixed qualitative methods of photo-elicitation, face to face interviews and semiotic analysis to uncover pre-service students' beliefs about young children. The researchers share their experience on conducting a study using photo-elicitation and engaging pre-service teachers in a discussion…

Dose- and Time-Dependent Transcriptional Response of Ishikawa Cells Exposed to Genistein.

PubMed

Naciff, Jorge M; Khambatta, Zubin S; Carr, Gregory J; Tiesman, Jay P; Singleton, David W; Khan, Sohaib A; Daston, George P

2016-05-01

To further define the utility of the Ishikawa cells as a reliable in vitro model to determine the potential estrogenic activity of chemicals of interest, transcriptional changes induced by genistein (GES) in Ishikawa cells at various doses (10 pM, 1 nM, 100 nM, and 10 μM) and time points (8, 24, and 48 h) were identified using a comprehensive microarray approach. Trend analysis indicated that the expression of 5342 unique genes was modified by GES in a dose- and time-dependent manner (P ≤ 0.0001). However, the majority of gene expression changes induced in Ishikawa cells were elicited by the highest dose of GES evaluated (10 μM). The GES' estrogenic activity was identified by comparing the Ishikawa cells' response to GES versus 17 α-ethynyl estradiol (EE, at equipotent doses, ie, 10 μM vs 1 μM, respectively) and was defined by changes in the expression of 284 unique genes elicited by GES and EE in the same direction, although the magnitude of the change for some genes was different. Further, comparing the response of the Ishikawa cells exposed to high doses of GES and EE versus the response of the juvenile rat uterus exposed to EE, we identified 66 unique genes which were up- or down regulated in a similar manner in vivo as well as in vitro Genistein elicits changes in multiple molecular pathways affecting various biological processes particularly associated with cell organization and biogenesis, regulation of translation, cell proliferation, and intracellular transport; processes also affected by estrogen exposure in the uterus of the rat. These results indicate that Ishikawa cells are capable of generating a biologically relevant estrogenic response and offer an in vitro model to assess this mode of action. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Unique Variants in OPN1LW Cause Both Syndromic and Nonsyndromic X-Linked High Myopia Mapped to MYP1.

PubMed

Li, Jiali; Gao, Bei; Guan, Liping; Xiao, Xueshan; Zhang, Jianguo; Li, Shiqiang; Jiang, Hui; Jia, Xiaoyun; Yang, Jianhua; Guo, Xiangming; Yin, Ye; Wang, Jun; Zhang, Qingjiong

2015-06-01

MYP1 is a locus for X-linked syndromic and nonsyndromic high myopia. Recently, unique haplotypes in OPN1LW were found to be responsible for X-linked syndromic high myopia mapped to MYP1. The current study is to test if such variants in OPN1LW are also responsible for X-linked nonsyndromic high myopia mapped to MYP1. The proband of the family previously mapped to MYP1 was initially analyzed using whole-exome sequencing and whole-genome sequencing. Additional probands with early-onset high myopia were analyzed using whole-exome sequencing. Variants in OPN1LW were selected and confirmed by Sanger sequencing. Long-range and second PCR were used to determine the haplotype and the first gene of the red-green gene array. Candidate variants were further validated in family members and controls. The unique LVAVA haplotype in OPN1LW was detected in the family with X-linked nonsyndromic high myopia mapped to MYP1. In addition, this haplotype and a novel frameshift mutation (c.617_620dup, p.Phe208Argfs*51) in OPN1LW were detected in two other families with X-linked high myopia. The unique haplotype cosegregated with high myopia in the two families, with a maximum LOD score of 3.34 and 2.31 at θ = 0. OPN1LW with the variants in these families was the first gene in the red-green gene array and was not present in 247 male controls. Reevaluation of the clinical data in both families with the unique haplotype suggested nonsyndromic high myopia. Our study confirms the findings that unique variants in OPN1LW are responsible for both syndromic and nonsyndromic X-linked high myopia mapped to MYP1.

“I see it now”: Using photo elicitation to understand chronic illness self-management

PubMed Central

Fritz, Heather; Lysack, Cathy

2018-01-01

Background How people integrate self-management into daily life remains underexamined, and such processes are difficult to elicit through traditional approaches used to understand human occupation. Purpose This paper will provide a brief overview of one visual research method, photo elicitation, that holds promise for studying self-management of health behaviours and will present findings from an analysis of how the use of photo elicitation interviews contributed additional insights into self-management beyond those generated from the data collected through the other methods used in the study. Method A qualitative, multiple-methods, multiple-case study was conducted with a purposive sample of 10 low-income women ages 40 to 64 with type 2 diabetes. Findings The photo elicitation interviews contributed insights beyond those generated from other study methods about how individuals viewed their self-management behaviours and how occupations changed across time. Implications Photo elicitation is a valuable research method for better understanding clients' chronic illness self-management practices. PMID:29898501

Eliciting nicotine craving with virtual smoking cues.

PubMed

Gamito, Pedro; Oliveira, Jorge; Baptista, André; Morais, Diogo; Lopes, Paulo; Rosa, Pedro; Santos, Nuno; Brito, Rodrigo

2014-08-01

Craving is a strong desire to consume that emerges in every case of substance addiction. Previous studies have shown that eliciting craving with an exposure cues protocol can be a useful option for the treatment of nicotine dependence. Thus, the main goal of this study was to develop a virtual platform in order to induce craving in smokers. Fifty-five undergraduate students were randomly assigned to two different virtual environments: high arousal contextual cues and low arousal contextual cues scenarios (17 smokers with low nicotine dependency were excluded). An eye-tracker system was used to evaluate attention toward these cues. Eye fixation on smoking-related cues differed between smokers and nonsmokers, indicating that smokers focused more often on smoking-related cues than nonsmokers. Self-reports of craving are in agreement with these results and suggest a significant increase in craving after exposure to smoking cues. In sum, these data support the use of virtual environments for eliciting craving.

The capsaicin cough reflex in eczema patients with respiratory symptoms elicited by perfume.

PubMed

Elberling, Jesper; Dirksen, Asger; Johansen, Jeanne Duus; Mosbech, Holger

2006-03-01

Respiratory symptoms elicited by perfume are common in the population but have unclear pathophysiology. Increased capsaicin cough responsiveness has been associated with the symptoms, but it is unknown whether the site of the symptoms in the airways influences this association. The aim of this study was to investigate the association between the site of airway symptoms elicited by perfume and cough responsiveness to bronchial challenge with capsaicin. 21 eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case control study. The participants completed a symptom questionnaire and underwent a bronchial challenge with capsaicin. Lower, but not upper, respiratory symptoms elicited by perfume were associated with increased capsaicin cough responsiveness. Having severe symptoms to perfume (n=11) did not relate to the site of the symptoms in the airways and was not associated with increased capsaicin cough responsiveness. In conclusion, respiratory symptoms elicited by perfume may reflect local hyperreactivity related to defensive reflexes in the airways, and measurements of the capsaicin cough reflex are relevant when patients with lower respiratory symptoms related to environmental perfume exposures are investigated.

RUCS: rapid identification of PCR primers for unique core sequences.

PubMed

Thomsen, Martin Christen Frølund; Hasman, Henrik; Westh, Henrik; Kaya, Hülya; Lund, Ole

2017-12-15

Designing PCR primers to target a specific selection of whole genome sequenced strains can be a long, arduous and sometimes impractical task. Such tasks would benefit greatly from an automated tool to both identify unique targets, and to validate the vast number of potential primer pairs for the targets in silico. Here we present RUCS, a program that will find PCR primer pairs and probes for the unique core sequences of a positive genome dataset complement to a negative genome dataset. The resulting primer pairs and probes are in addition to simple selection also validated through a complex in silico PCR simulation. We compared our method, which identifies the unique core sequences, against an existing tool called ssGeneFinder, and found that our method was 6.5-20 times more sensitive. We used RUCS to design primer pairs that would target a set of genomes known to contain the mcr-1 colistin resistance gene. Three of the predicted pairs were chosen for experimental validation using PCR and gel electrophoresis. All three pairs successfully produced an amplicon with the target length for the samples containing mcr-1 and no amplification products were produced for the negative samples. The novel methods presented in this manuscript can reduce the time needed to identify target sequences, and provide a quick virtual PCR validation to eliminate time wasted on ambiguously binding primers. Source code is freely available on https://bitbucket.org/genomicepidemiology/rucs. Web service is freely available on https://cge.cbs.dtu.dk/services/RUCS. mcft@cbs.dtu.dk. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Glucose deprivation elicits phenotypic plasticity via ZEB1-mediated expression of NNMT

PubMed Central

Kanska, Justyna; Aspuria, Paul-Joseph P.; Taylor-Harding, Barbie; Spurka, Lindsay; Funari, Vincent; Orsulic, Sandra; Karlan, Beth Y.; Wiedemeyer, W. Ruprecht

2017-01-01

Glucose is considered the primary energy source for all cells, and some cancers are addicted to glucose. Here, we investigated the functional consequences of chronic glucose deprivation in serous ovarian cancer cells. We found that cells resistant to glucose starvation (glucose-restricted cells) demonstrated increased metabolic plasticity that was dependent on NNMT (Nicotinamide N-methyltransferase) expression. We further show that ZEB1 induced NNMT, rendered cells resistant to glucose deprivation and recapitulated metabolic adaptations and mesenchymal gene expression observed in glucose-restricted cells. NNMT depletion reversed metabolic plasticity in glucose-restricted cells and prevented de novo formation of glucose-restricted colonies. In addition to its role in glucose independence, we found that NNMT was required for other ZEB1-induced phenotypes, such as increased migration. NNMT protein levels were also elevated in metastatic and recurrent tumors compared to matched primary carcinomas, while normal ovary and fallopian tube tissue had no detectable NNMT expression. Our studies define a novel ZEB1/NNMT signaling axis, which elicits mesenchymal gene expression, as well as phenotypic and metabolic plasticity in ovarian cancer cells upon chronic glucose starvation. Understanding the causes of cancer cell plasticity is crucial for the development of therapeutic strategies to counter intratumoral heterogeneity, acquired drug resistance and recurrence in high-grade serous ovarian cancer (HGSC). PMID:28412735

CXCL4 induces a unique transcriptome in monocyte-derived macrophages

PubMed Central

Gleissner, Christian A.; Shaked, Iftach; Little, Kristina M.; Ley, Klaus

2012-01-01

In atherosclerotic arteries, blood monocytes differentiate to macrophages in the presence of growth factors like macrophage colony-stimulation factor (MCSF) and chemokines like platelet factor 4 (CXCL4). To compare the gene expression signature of CXCL4-induced macrophages with MCSF-induced macrophages or macrophages polarized with IFN-γ/LPS (M1) or IL-4 (M2), we cultured primary human peripheral blood monocytes for six days. mRNA expression was measured by Affymetrix gene chips and differences were analyzed by Local Pooled Error test, Profile of Complex Functionality and Gene Set Enrichment Analysis. 375 genes were differentially expressed between MCSF- and CXCL4-induced macrophages, 206 of them overexpressed in CXCL4 macrophages coding for genes implicated in the inflammatory/immune response, antigen processing/presentation, and lipid metabolism. CXCL4-induced macrophages overexpressed some M1 and M2 genes and the corresponding cytokines at the protein level, however, their transcriptome clustered with neither M1 nor M2 transcriptomes. They almost completely lost the ability to phagocytose zymosan beads. Genes linked to atherosclerosis were not consistently up- or downregulated. Scavenger receptors showed lower and cholesterol efflux transporters higher expression in CXCL4- than MCSF-induced macrophages, resulting in lower LDL content. We conclude that CXCL4 induces a unique macrophage transcriptome distinct from known macrophage types, defining a new macrophage differentiation that we propose to call M4. PMID:20335529

Sequencing rare marine actinomycete genomes reveals high density of unique natural product biosynthetic gene clusters.

PubMed

Schorn, Michelle A; Alanjary, Mohammad M; Aguinaldo, Kristen; Korobeynikov, Anton; Podell, Sheila; Patin, Nastassia; Lincecum, Tommie; Jensen, Paul R; Ziemert, Nadine; Moore, Bradley S

2016-12-01

Traditional natural product discovery methods have nearly exhausted the accessible diversity of microbial chemicals, making new sources and techniques paramount in the search for new molecules. Marine actinomycete bacteria have recently come into the spotlight as fruitful producers of structurally diverse secondary metabolites, and remain relatively untapped. In this study, we sequenced 21 marine-derived actinomycete strains, rarely studied for their secondary metabolite potential and under-represented in current genomic databases. We found that genome size and phylogeny were good predictors of biosynthetic gene cluster diversity, with larger genomes rivalling the well-known marine producers in the Streptomyces and Salinispora genera. Genomes in the Micrococcineae suborder, however, had consistently the lowest number of biosynthetic gene clusters. By networking individual gene clusters into gene cluster families, we were able to computationally estimate the degree of novelty each genus contributed to the current sequence databases. Based on the similarity measures between all actinobacteria in the Joint Genome Institute's Atlas of Biosynthetic gene Clusters database, rare marine genera show a high degree of novelty and diversity, with Corynebacterium, Gordonia, Nocardiopsis, Saccharomonospora and Pseudonocardia genera representing the highest gene cluster diversity. This research validates that rare marine actinomycetes are important candidates for exploration, as they are relatively unstudied, and their relatives are historically rich in secondary metabolites.

Sequencing rare marine actinomycete genomes reveals high density of unique natural product biosynthetic gene clusters

PubMed Central

Schorn, Michelle A.; Alanjary, Mohammad M.; Aguinaldo, Kristen; Korobeynikov, Anton; Podell, Sheila; Patin, Nastassia; Lincecum, Tommie; Jensen, Paul R.; Ziemert, Nadine

2016-01-01

Traditional natural product discovery methods have nearly exhausted the accessible diversity of microbial chemicals, making new sources and techniques paramount in the search for new molecules. Marine actinomycete bacteria have recently come into the spotlight as fruitful producers of structurally diverse secondary metabolites, and remain relatively untapped. In this study, we sequenced 21 marine-derived actinomycete strains, rarely studied for their secondary metabolite potential and under-represented in current genomic databases. We found that genome size and phylogeny were good predictors of biosynthetic gene cluster diversity, with larger genomes rivalling the well-known marine producers in the Streptomyces and Salinispora genera. Genomes in the Micrococcineae suborder, however, had consistently the lowest number of biosynthetic gene clusters. By networking individual gene clusters into gene cluster families, we were able to computationally estimate the degree of novelty each genus contributed to the current sequence databases. Based on the similarity measures between all actinobacteria in the Joint Genome Institute's Atlas of Biosynthetic gene Clusters database, rare marine genera show a high degree of novelty and diversity, with Corynebacterium, Gordonia, Nocardiopsis, Saccharomonospora and Pseudonocardia genera representing the highest gene cluster diversity. This research validates that rare marine actinomycetes are important candidates for exploration, as they are relatively unstudied, and their relatives are historically rich in secondary metabolites. PMID:27902408

Eliciting and maintaining ruminative thought: the role of social-evaluative threat.

PubMed

Zoccola, Peggy M; Dickerson, Sally S; Lam, Suman

2012-08-01

This study tested whether a performance stressor characterized by social-evaluative threat (SET) elicits more rumination than a stressor without this explicit evaluative component and whether this difference persists minutes, hours, and days later. The mediating role of shame-related cognition and emotion (SRCE) was also examined. During a laboratory visit, 144 undergraduates (50% female) were randomly assigned to complete a speech stressor in a social-evaluative threat condition (SET; n = 86), in which an audience was present, or a nonexplicit social-evaluative threat condition (ne-SET; n = 58), in which they were alone in a room. Participants completed measures of stressor-related rumination 10 and 40 min posttask, later that night, and upon returning to the laboratory 3-5 days later. SRCE and other emotions experienced during the stressor (fear, anger, and sadness) were assessed immediately posttask. As hypothesized, the SET speech stressor elicited more rumination than the ne-SET speech stressor, and these differences persisted for 3-5 days. SRCE-but not other specific negative emotions or general emotional arousal-mediated the effect of stressor context on rumination. Stressors characterized by SET may be likely candidates for eliciting and maintaining ruminative thought immediately and also days later, potentially by eliciting shame-related emotions and cognitions.

Four Genes of Medicago truncatula Controlling Components of a Nod Factor Transduction Pathway

PubMed Central

Catoira, Romy; Galera, Christine; de Billy, Francoise; Penmetsa, R. Varma; Journet, Etienne-Pascal; Maillet, Fabienne; Rosenberg, Charles; Cook, Douglas; Gough, Clare; Dénarié, Jean

2000-01-01

Rhizobium nodulation (Nod) factors are lipo-chitooligosaccharides that act as symbiotic signals, eliciting several key developmental responses in the roots of legume hosts. Using nodulation-defective mutants of Medicago truncatula, we have started to dissect the genetic control of Nod factor transduction. Mutants in four genes (DMI1, DMI2, DMI3, and NSP) were pleiotropically affected in Nod factor responses, indicating that these genes are required for a Nod factor–activated signal transduction pathway that leads to symbiotic responses such as root hair deformations, expressions of nodulin genes, and cortical cell divisions. Mutant analysis also provides evidence that Nod factors have a dual effect on the growth of root hair: inhibition of endogenous (plant) tip growth, and elicitation of a novel tip growth dependent on (bacterial) Nod factors. dmi1, dmi2, and dmi3 mutants are also unable to establish a symbiotic association with endomycorrhizal fungi, indicating that there are at least three common steps to nodulation and endomycorrhization in M. truncatula and providing further evidence for a common signaling pathway between nodulation and mycorrhization. PMID:11006338

7α-Hydroxycholesterol Elicits TLR6-Mediated Expression of IL-23 in Monocytic Cells.

PubMed

Seo, Hyun Chul; Kim, Sun-Mi; Eo, Seong-Kug; Rhim, Byung-Yong; Kim, Koanhoi

2015-01-01

We investigated the question of whether 7-oxygenated cholesterol derivatives could affect inflammatory and/or immune responses in atherosclerosis by examining their effects on expression of IL-23 in monocytic cells. 7α-Hydroxycholesterol (7αOHChol) induced transcription of the TLR6 gene and elevated the level of cell surface TLR6 protein in THP-1 monocytic cells. Addition of an agonist of TLR6, FSL-1, to TLR6-expressing cells by treatment with 7αOHChol resulted in enhanced production of IL-23 and transcription of genes encoding the IL-23 subunit α (p19) and the IL-12 subunit β (p40). However, treatment with 7-ketocholesterol (7K) and 7β-hydroxycholesterol (7βOHChol) did not affect TLR6 expression, and addition of FSL-1 to cells treated with either 7K or 7βOHChol did not influence transcription of the genes. Pharmacological inhibition of ERK, Akt, or PI3K resulted in attenuated transcription of TLR6 induced by 7αOHChol as well as secretion of IL-23 enhanced by 7αOHChol plus FSL-1. Inhibition of p38 MAPK or JNK resulted in attenuated secretion of IL-23. These results indicate that a certain type of 7-oxygenated cholesterol like 7αOHChol can elicit TLR6-mediated expression of IL-23 by monocytic cells via PI3K/Akt and MAPKs pathways.

7α-Hydroxycholesterol Elicits TLR6-Mediated Expression of IL-23 in Monocytic Cells

PubMed Central

Seo, Hyun Chul; Kim, Sun-Mi; Eo, Seong-Kug; Rhim, Byung-Yong; Kim, Koanhoi

2015-01-01

We investigated the question of whether 7-oxygenated cholesterol derivatives could affect inflammatory and/or immune responses in atherosclerosis by examining their effects on expression of IL-23 in monocytic cells. 7α-Hydroxycholesterol (7αOHChol) induced transcription of the TLR6 gene and elevated the level of cell surface TLR6 protein in THP-1 monocytic cells. Addition of an agonist of TLR6, FSL-1, to TLR6-expressing cells by treatment with 7αOHChol resulted in enhanced production of IL-23 and transcription of genes encoding the IL-23 subunit α (p19) and the IL-12 subunit β (p40). However, treatment with 7-ketocholesterol (7K) and 7β-hydroxycholesterol (7βOHChol) did not affect TLR6 expression, and addition of FSL-1 to cells treated with either 7K or 7βOHChol did not influence transcription of the genes. Pharmacological inhibition of ERK, Akt, or PI3K resulted in attenuated transcription of TLR6 induced by 7αOHChol as well as secretion of IL-23 enhanced by 7αOHChol plus FSL-1. Inhibition of p38 MAPK or JNK resulted in attenuated secretion of IL-23. These results indicate that a certain type of 7-oxygenated cholesterol like 7αOHChol can elicit TLR6-mediated expression of IL-23 by monocytic cells via PI3K/Akt and MAPKs pathways. PMID:25593648

Exclusive Association of p53 Mutation with Super-High Methylation of Tumor Suppressor Genes in the p53 Pathway in a Unique Gastric Cancer Phenotype.

PubMed

Waraya, Mina; Yamashita, Keishi; Ema, Akira; Katada, Natsuya; Kikuchi, Shiro; Watanabe, Masahiko

2015-01-01

A comprehensive search for DNA methylated genes identified candidate tumor suppressor genes that have been proven to be involved in the apoptotic process of the p53 pathway. In this study, we investigated p53 mutation in relation to such epigenetic alteration in primary gastric cancer. The methylation profiles of the 3 genes: PGP9.5, NMDAR2B, and CCNA1, which are involved in the p53 tumor suppressor pathway in combination with p53 mutation were examined in 163 primary gastric cancers. The effect of epigenetic reversion in combination with chemotherapeutic drugs on apoptosis was also assessed according to the tumor p53 mutation status. p53 gene mutations were found in 44 primary gastric tumors (27%), and super-high methylation of any of the 3 genes was only found in cases with wild type p53. Higher p53 pathway aberration was found in cases with male gender (p = 0.003), intestinal type (p = 0.005), and non-infiltrating type (p = 0.001). The p53 pathway aberration group exhibited less recurrence in lymph nodes, distant organs, and peritoneum than the p53 non-aberration group. In the NUGC4 gastric cancer cell line (p53 wild type), epigenetic treatment augmented apoptosis by chemotherapeutic drugs, partially through p53 transcription activity. On the other hand, in the KATO III cancer cell line (p53 mutant), epigenetic treatment alone induced robust apoptosis, with no trans-activation of p53. In gastric cancer, p53 relevant and non-relevant pathways exist, and tumors with either pathway type exhibited unique clinical features. Epigenetic treatments can induce apoptosis partially through p53 activation, however their apoptotic effects may be explained largely by mechanism other than through p53 pathways.

Unique differentiation profile of mouse embryonic stem cells in rotary and stirred tank bioreactors.

PubMed

Fridley, Krista M; Fernandez, Irina; Li, Mon-Tzu Alice; Kettlewell, Robert B; Roy, Krishnendu

2010-11-01

Embryonic stem (ES)-cell-derived lineage-specific stem cells, for example, hematopoietic stem cells, could provide a potentially unlimited source for transplantable cells, especially for cell-based therapies. However, reproducible methods must be developed to maximize and scale-up ES cell differentiation to produce clinically relevant numbers of therapeutic cells. Bioreactor-based dynamic culture conditions are amenable to large-scale cell production, but few studies have evaluated how various bioreactor types and culture parameters influence ES cell differentiation, especially hematopoiesis. Our results indicate that cell seeding density and bioreactor speed significantly affect embryoid body formation and subsequent generation of hematopoietic stem and progenitor cells in both stirred tank (spinner flask) and rotary microgravity (Synthecon™) type bioreactors. In general, high percentages of hematopoietic stem and progenitor cells were generated in both bioreactors, especially at high cell densities. In addition, Synthecon bioreactors produced more sca-1(+) progenitors and spinner flasks generated more c-Kit(+) progenitors, demonstrating their unique differentiation profiles. cDNA microarray analysis of genes involved in pluripotency, germ layer formation, and hematopoietic differentiation showed that on day 7 of differentiation, embryoid bodies from both bioreactors consisted of all three germ layers of embryonic development. However, unique gene expression profiles were observed in the two bioreactors; for example, expression of specific hematopoietic genes were significantly more upregulated in the Synthecon cultures than in spinner flasks. We conclude that bioreactor type and culture parameters can be used to control ES cell differentiation, enhance unique progenitor cell populations, and provide means for large-scale production of transplantable therapeutic cells.

Dysfunctional BLK in common variable immunodeficiency perturbs B-cell proliferation and ability to elicit antigen-specific CD4+ T-cell help.

PubMed

Compeer, Ewoud B; Janssen, Willemijn; van Royen-Kerkhof, Annet; van Gijn, Marielle; van Montfrans, Joris M; Boes, Marianne

2015-05-10

Common Variable Immunodeficiency (CVID) is the most prevalent primary antibody deficiency, and characterized by defective generation of high-affinity antibodies. Patients have therefore increased risk to recurrent infections of the respiratory and intestinal tract. Development of high-affinity antigen-specific antibodies involves two key actions of B-cell receptors (BCR): transmembrane signaling through BCR-complexes to induce B-cell differentiation and proliferation, and BCR-mediated antigen internalization for class-II MHC-mediated presentation to acquire antigen-specific CD4(+) T-cell help.We identified a variant (L3P) in the B-lymphoid tyrosine kinase (BLK) gene of 2 related CVID-patients, which was absent in healthy relatives. BLK belongs to the Src-kinases family and involved in BCR-signaling. Here, we sought to clarify BLK function in healthy human B-cells and its association to CVID.BLK expression was comparable in patient and healthy B-cells. Functional analysis of L3P-BLK showed reduced BCR crosslinking-induced Syk phosphorylation and proliferation, in both primary B-cells and B-LCLs. B-cells expressing L3P-BLK showed accelerated destruction of BCR-internalized antigen and reduced ability to elicit CD40L-expression on antigen-specific CD4(+) T-cells.In conclusion, we found a novel BLK gene variant in CVID-patients that causes suppressed B-cell proliferation and reduced ability of B-cells to elicit antigen-specific CD4(+) T-cell responses. Both these mechanisms may contribute to hypogammaglobulinemia in CVID-patients.

TSLP-elicited basophil responses can mediate the pathogenesis of eosinophilic esophagitis

PubMed Central

Noti, Mario; Tait Wojno, Elia D.; Kim, Brian S.; Siracusa, Mark C.; Giacomin, Paul R.; Nair, Meera G.; Benitez, Alain J.; Ruymann, Kathryn R.; Muir, Amanda B.; Hill, David A.; Chikwava, Kudakwashe R.; Moghaddam, Amin E.; Sattentau, Quentin J.; Alex, Aneesh; Zhou, Chao; Yearley, Jennifer H.; Menard-Katcher, Paul; Kubo, Masato; Obata-Ninomiya, Kazushige; Karasuyama, Hajime; Comeau, Michael R.; Brown-Whitehorn, Terri; de Waal Malefyt, Rene; Sleiman, Patrick M.; Hakonarson, Hakon; Cianferoni, Antonella; Falk, Gary W.; Wang, Mei-Lun; Spergel, Jonathan M.; Artis, David

2014-01-01

Eosinophilic esophagitis (EoE) is a food allergy-associated inflammatory disease characterized by esophageal eosinophilia. EoE has become increasingly common, but current management strategies are nonspecific. Thus, there is an urgent need to identify specific immunological pathways that could be targeted to treat this disease. EoE is associated with polymorphisms in the gene that encodes thymic stromal lymphopoietin (TSLP), a cytokine that promotes allergic inflammation, but how TSLP might contribute to EoE disease pathogenesis remains unknown. Here, we describe a new mouse model of EoE-like disease that developed independently of IgE but was dependent on TSLP-elicited basophils. Therapeutic TSLP neutralization or basophil depletion also ameliorated established EoE-like disease. Critically, in human subjects with EoE, we observed elevated TSLP levels and exaggerated basophil responses in esophageal biopsies, and a gain-of-function TSLP polymorphism was associated with increased basophil responses. Together, these data suggest that the TSLP-basophil axis could be therapeutically targeted to treat EoE. PMID:23872715

RNA Expression Analysis of Passive Transfer Myasthenia Supports Extraocular Muscle as a Unique Immunological Environment

PubMed Central

Zhou, Yuefang; Kaminski, Henry J.; Gong, Bendi; Cheng, Georgiana; Feuerman, Jason M.; Kusner, Linda

2014-01-01

Purpose. Myasthenia gravis demonstrates a distinct predilection for involvement of the extraocular muscles (EOM), and we have hypothesized that this may be due to a unique immunological environment. To assess this hypothesis, we took an unbiased approach to analyze RNA expression profiles in EOM, diaphragm, and extensor digitorum longus (EDL) in rats with experimentally acquired myasthenia gravis (EAMG). Methods. Experimentally acquired myasthenia gravis was induced in rats by intraperitoneal injection of antibody directed against the acetylcholine receptor (AChR), whereas control rats received antibody known to bind the AChR but not induce disease. After 48 hours, animals were killed and muscles analyzed by RNA expression profiling. Profiling results were validated using qPCR and immunohistochemical analysis. Results. Sixty-two genes common among all muscle groups were increased in expression. These fell into four major categories: 12.8% stress response, 10.5% immune response, 10.5% metabolism, and 9.0% transcription factors. EOM expressed 212 genes at higher levels, not shared by the other two muscles, and a preponderance of EOM gene changes fell into the immune response category. EOM had the most uniquely reduced genes (126) compared with diaphragm (26) and EDL (50). Only 18 downregulated genes were shared by the three muscles. Histological evaluation and disease load index (sum of fold changes for all genes) demonstrated that EOM had the greatest degree of pathology. Conclusions. Our studies demonstrated that consistent with human myasthenia gravis, EOM demonstrates a distinct RNA expression signature from EDL and diaphragm, which is based on differences in the degree of muscle injury and inflammatory response. PMID:24917137

GeneSigDB—a curated database of gene expression signatures

PubMed Central

Culhane, Aedín C.; Schwarzl, Thomas; Sultana, Razvan; Picard, Kermshlise C.; Picard, Shaita C.; Lu, Tim H.; Franklin, Katherine R.; French, Simon J.; Papenhausen, Gerald; Correll, Mick; Quackenbush, John

2010-01-01

The primary objective of most gene expression studies is the identification of one or more gene signatures; lists of genes whose transcriptional levels are uniquely associated with a specific biological phenotype. Whilst thousands of experimentally derived gene signatures are published, their potential value to the community is limited by their computational inaccessibility. Gene signatures are embedded in published article figures, tables or in supplementary materials, and are frequently presented using non-standard gene or probeset nomenclature. We present GeneSigDB (http://compbio.dfci.harvard.edu/genesigdb) a manually curated database of gene expression signatures. GeneSigDB release 1.0 focuses on cancer and stem cells gene signatures and was constructed from more than 850 publications from which we manually transcribed 575 gene signatures. Most gene signatures (n = 560) were successfully mapped to the genome to extract standardized lists of EnsEMBL gene identifiers. GeneSigDB provides the original gene signature, the standardized gene list and a fully traceable gene mapping history for each gene from the original transcribed data table through to the standardized list of genes. The GeneSigDB web portal is easy to search, allows users to compare their own gene list to those in the database, and download gene signatures in most common gene identifier formats. PMID:19934259

Elicitation Support Requirements of Multi-Expertise Teams

ERIC Educational Resources Information Center

Bitter-Rijpkema, Marlies; Martens, Rob; Jochems, Wim

2005-01-01

Tools to support knowledge elicitation are used more and more in situations where employees or students collaborate using the computer. Studies indicate that differences exist between experts and novices regarding their methods of work and reasoning. However, the commonly preferred approach tends to deal with team members as a single system with…

Elicitation of andrographolide in the suspension cultures of Andrographis paniculata.

PubMed

Gandi, Suryakala; Rao, Kiranmayee; Chodisetti, Bhuvaneswari; Giri, Archana

2012-12-01

Andrographis paniculata belonging to the family Acanthaceae produces a group of diterpene lactones, one of which is the pharmaceutically important-andrographolide. It is known to possess various important biological properties like anticancer, anti-HIV, anti-inflammatory, etc. This is the first report on the production of andrographolide in the cell suspension cultures of Andrographis paniculata by 'elicitation'. Elicitation was attempted to enhance the andrographolide content in the suspension cultures of Andrographis paniculata and also to ascertain its stimulation under stress conditions or in response to pathogen attack. The maximum andrographolide production was found to be 1.53 mg/g dry cell weight (DCW) at the end of stationary phase during the growth curve. The biotic elicitors (yeast, Escherichia coli, Bacillus subtilis, Agrobacterium rhizogenes 532 and Agrobacterium tumefaciens C 58) were more effective in eliciting the response when compared to the abiotic elicitors (CdCl(2), AgNO(3), CuCl(2) and HgCl(2)). Yeast has shown to stimulate maximum accumulation of 13.5 mg/g DCW andrographolide, which was found to be 8.82-fold higher than the untreated cultures.

Comparison of elicitation methods for moral and affective beliefs in the theory of planned behaviour.

PubMed

Dean, M; Arvola, A; Vassallo, M; Lähteenmäki, L; Raats, M M; Saba, A; Shepherd, R

2006-09-01

Although the theory of planned behaviour (TPB) has been applied successfully in the area of food choice, it has been criticized for its pure utilitarian approach to the factors determining behaviour. Despite the increase in predictive power of the model with added components such as affective attitude and moral and ethical concerns, in most studies the elicitation process still only addresses people's utilitarian beliefs about the behaviour with little attention paid to other aspects. This study compares the traditional method of elicitation of advantages and disadvantages with two other methods (word association and open-ended) in the elicitations of beliefs, attitudes and moral concerns in relation to the consumption of organic foods. Results show the traditional method to be best for eliciting cognitive beliefs, open-ended emotion task for eliciting emotional beliefs and open-ended beliefs task best for moral concerns. The advantages and disadvantages of each method are discussed.

Unique variations of Epstein-Barr virus-encoded BARF1 gene in nasopharyngeal carcinoma biopsies.

PubMed

Wang, Yun; Wang, Xiao-Feng; Sun, Zhi-Fu; Luo, Bing

2012-06-01

The Epstein-Barr virus (EBV) BamHI-A rightward frame 1 (BARF1) gene is frequently expressed in EBV-associated epithelial malignancies and involves in oncogenicity and immunomodulation. To characterize the variations of BARF1 gene in different populations, the sequences of BARF1 gene in Northern Chinese nasopharyngeal carcinoma (NPC), EBV-associated gastric carcinoma (EBVaGC) and healthy donors were analyzed. The correlation of BARF1 variation with polymorphisms of BamHI F fragment (type F and f variants) and EBV-coded viral interleukin-10 (vIL-10) gene (B95-8 and SPM patterns) was also explored. Two major subtypes of BARF1 gene, designated as B95-8 and V29A, were identified. B95-8 subtype had identical amino acid sequence to B95-8 and was the dominant subtype among the EBV isolates from Northern China. V29A subtype, with one consistent amino acid change at residue 29 (V→A) and several nucleotide changes, showed higher frequency in NPC cases (25.3%, 20/79) than in EBVaGC cases (0/45) or healthy donors (4.3%, 2/46) (NPC vs. EBVaGC: P=0.0001; NPC vs. healthy donor: P=0.004). A preferential linkage between BamHI F and BARF1/vIL-10 polymorphisms was found. Type f isolates was specially correlated with the V29A/SPM genotype in NPC isolates and type f/V29A/SPM was preferentially found in NPC. BARF1/c-fms homology domain, transforming domain and cytotoxic T lymphocyte (CTL) epitopes of BARF1 were highly conserved in most isolates, suggesting the important role of BARF1 in virus infection and the potential usefulness in EBV-targeting immunotherapy of EBV-associated tumors. The relatively higher prevalence of type f/V29A/SPM strains in NPC may also suggest the association between these variations in multiple viral genes and NPC. Copyright © 2012 Elsevier B.V. All rights reserved.

Elicitation of spreading depression by rose bengal photodynamic action.

PubMed

Netto, M; Martins-Ferreira, H

1989-08-01

Spreading depression refers to a slowly propagating depression of the ordinary electrical activity of the nervous tissue. It can be elicited by different types of physical or chemical non-specific stimuli. Various evidences suggest that transient alterations of cell membranes are involved. For this reason, and considering the action of free radicals on cell membranes, the elicitation of the reaction by dye photoactivation has been investigated. Isolated chick retina superfused in the dark with Ringer solution was able to regularly exhibit spreading depression when submitted to 1 microM rose bengal pulse of 5 min in duration, followed by 2.1 x 10(4) to 4.2 x 10(4) Jm-2 light pulse. The phenomenon was monitored either by visual inspection of the light-scattering milky wave that accompanies the reaction or by recording its characteristic slow voltage variation. The reaction was not triggered if the retina, superfused with the dye, was (a) maintained in the dark; (b) illuminated with red light (3.75 x 10(2) to 2.25 x 10(4) Jm-2), or (c) stimulated by white light but superfused with nitrogen-saturated solutions. It is concluded that, under the present conditions, the elicitation of spreading depression is contingent on the photoactivation of rose bengal in the presence of oxygen.

The genome of Mesobuthus martensii reveals a unique adaptation model of arthropods

PubMed Central

Cao, Zhijian; Yu, Yao; Wu, Yingliang; Hao, Pei; Di, Zhiyong; He, Yawen; Chen, Zongyun; Yang, Weishan; Shen, Zhiyong; He, Xiaohua; Sheng, Jia; Xu, Xiaobo; Pan, Bohu; Feng, Jing; Yang, Xiaojuan; Hong, Wei; Zhao, Wenjuan; Li, Zhongjie; Huang, Kai; Li, Tian; Kong, Yimeng; Liu, Hui; Jiang, Dahe; Zhang, Binyan; Hu, Jun; Hu, Youtian; Wang, Bin; Dai, Jianliang; Yuan, Bifeng; Feng, Yuqi; Huang, Wei; Xing, Xiaojing; Zhao, Guoping; Li, Xuan; Li, Yixue; Li, Wenxin

2013-01-01

Representing a basal branch of arachnids, scorpions are known as ‘living fossils’ that maintain an ancient anatomy and are adapted to have survived extreme climate changes. Here we report the genome sequence of Mesobuthus martensii, containing 32,016 protein-coding genes, the most among sequenced arthropods. Although M. martensii appears to evolve conservatively, it has a greater gene family turnover than the insects that have undergone diverse morphological and physiological changes, suggesting the decoupling of the molecular and morphological evolution in scorpions. Underlying the long-term adaptation of scorpions is the expansion of the gene families enriched in basic metabolic pathways, signalling pathways, neurotoxins and cytochrome P450, and the different dynamics of expansion between the shared and the scorpion lineage-specific gene families. Genomic and transcriptomic analyses further illustrate the important genetic features associated with prey, nocturnal behaviour, feeding and detoxification. The M. martensii genome reveals a unique adaptation model of arthropods, offering new insights into the genetic bases of the living fossils. PMID:24129506

A unique mosaic Turner syndrome patient with androgen receptor gene derived marker chromosome.

PubMed

Kalkan, Rasime; Özdağ, Nermin; Bundak, Rüveyde; Çirakoğlu, Ayşe; Serakinci, Nedime

2016-01-01

Patients with Turner syndrome are generally characterized by having short stature with no secondary sexual characteristics. Some abnormalities, such as webbed neck, renal malformations (>50%) and cardiac defects (10%) are less common. The intelligence of these patients is considered normal. Non-mosaic monosomy X is observed in approximately 45% of postnatal patients with Turner syndrome and the rest of the patients have structural abnormalities or mosaicism involving 46,X,i(Xq), 45,X/46,XX, 45,X and other variants. The phenotype of 45,X/46,X,+mar individuals varies by the genetic continent and degree of the mosaicism. The gene content of the marker chromosome is the most important when correlating the phenotype with the genotype. Here we present an 11-year-old female who was referred for evaluation of her short stature and learning disabilities. Conventional cytogenetic investigation showed a mosaic 45,X/46,X,+mar karyotype. Fluorescence in situ hybridization showed that the marker chromosome originated from the X chromosome within the androgen receptor (AR) and X-inactive specific transcript (XIST) genes. Therefore, it is possible that aberrant activation of the marker chromosome, compromising the AR and XIST genes, may modify the Turner syndrome phenotype.

Targeting Unique Metabolic Properties of Breast Tumor Initiating Cells

PubMed Central

Feng, Weiguo; Gentles, Andrew; Nair, Ramesh V.; Huang, Min; Lin, Yuan; Lee, Cleo Y.; Cai, Shang; Scheeren, Ferenc A.; Kuo, Angera H.; Diehn, Maximilian

2014-01-01

Normal stem cells from a variety of tissues display unique metabolic properties compared to their more differentiated progeny. However, relatively little is known about heterogeneity of metabolic properties cancer stem cells, also called tumor initiating cells (TICs). In this study we show that, analogous to some normal stem cells, breast TICs have distinct metabolic properties compared to non-tumorigenic cancer cells (NTCs). Transcriptome profiling using RNA-Seq revealed TICs under-express genes involved in mitochondrial biology and mitochondrial oxidative phosphorylation and metabolic analyses revealed TICs preferentially perform glycolysis over oxidative phosphorylation compared to NTCs. Mechanistic analyses demonstrated that decreased expression and activity of pyruvate dehydrogenase (Pdh), a key regulator of oxidative phosphorylation, play a critical role in promoting the pro-glycolytic phenotype of TICs. Metabolic reprogramming via forced activation of Pdh preferentially eliminates TICs both in vitro and in vivo. Our findings reveal unique metabolic properties of TICs and demonstrate that metabolic reprogramming represents a promising strategy for targeting these cells. PMID:24497069

Apoptosis Gene Information System--AGIS.

PubMed

Sakharkar, Kishore R; Clement, Marie V; Chow, Vincent T K; Pervaiz, Shazib

2006-05-01

Genes implicated in apoptosis have great relevance to biology, medicine and oncology. Here, we describe a unique resource, Apoptosis Gene Information System (AGIS) that provides data for over 2400 genes involved directly or indirectly, in apoptotic pathways of more than 350 different organisms. The organization of this information system is based on the principle of one-gene, one record. AGIS will be updated on a six monthly basis as new information becomes available. AGIS can be accessed at: http://www.cellfate.org/AGIS/.

Identifying and Responding to Personal Stressors: Utilizing Photo Elicitation in Health Education Courses

ERIC Educational Resources Information Center

Hunter, Theresa

2014-01-01

The "Photo Elicitation Project" teaching idea applies the techniques of photo elicitation to stress prevention and management. This activity is designed to help students identify their personal stressors and to determine which stress prevention strategies are most useful for them. Objectives: students will be able to (a) identify current…

Stone Soup: Photo-Elicitation as a Learning Tool in the Food Geography Classroom

ERIC Educational Resources Information Center

Kurtz, Hilda E.; Wood, Jason

2014-01-01

This paper showcases self-reflective and inclusive pedagogy using photo-elicitation in a food geography course assignment. The Stone Soup project positions students as both researchers and participant-subjects in a participant-driven photo-elicitation (PDPE) study of students' foodways. Student papers for this assignment demonstrate rich…

Sustained Hypoxia Elicits Competing Spinal Mechanisms of Phrenic Motor Facilitation

PubMed Central

Devinney, Michael J.; Nichols, Nicole L.

2016-01-01

Acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF), a form of spinal motor plasticity. Competing mechanisms give rise to phrenic motor facilitation (pMF; a general term including pLTF) depending on the severity of hypoxia within episodes. In contrast, moderate acute sustained hypoxia (mASH) does not elicit pMF. By varying the severity of ASH and targeting competing mechanisms of pMF, we sought to illustrate why moderate AIH (mAIH) elicits pMF but mASH does not. Although mAIH elicits serotonin-dependent pLTF, mASH does not; thus, mAIH-induced pLTF is pattern sensitive. In contrast, severe AIH (sAIH) elicits pLTF through adenosine-dependent mechanisms, likely from greater extracellular adenosine accumulation. Because serotonin- and adenosine-dependent pMF interact via cross talk inhibition, we hypothesized that pMF is obscured because the competing mechanisms of pMF are balanced and offsetting during mASH. Here, we demonstrate the following: (1) blocking spinal A2A receptors with MSX-3 reveals mASH-induced pMF; and (2) sASH elicits A2A-dependent pMF. In anesthetized rats pretreated with intrathecal A2A receptor antagonist injections before mASH (PaO2 = 40–54 mmHg) or sASH (PaO2 = 25–36 mmHg), (1) mASH induced a serotonin-dependent pMF and (2) sASH induced an adenosine-dependent pMF, which was enhanced by spinal serotonin receptor inhibition. Thus, competing adenosine- and serotonin-dependent mechanisms contribute differentially to pMF depending on the pattern/severity of hypoxia. Understanding interactions between these mechanisms has clinical relevance as we develop therapies to treat severe neuromuscular disorders that compromise somatic motor behaviors, including breathing. Moreover, these results demonstrate how competing mechanisms of plasticity can give rise to pattern sensitivity in pLTF. SIGNIFICANCE STATEMENT Intermittent hypoxia elicits pattern-sensitive spinal plasticity and improves motor function after spinal injury or

Realistic Real World Contexts: Model Eliciting Activities

ERIC Educational Resources Information Center

Doruk, Bekir Kürsat

2016-01-01

Researchers have proposed a variety of methods to make a connection between real life and mathematics so that it can be learned in a practical way and enable people to utilise mathematics in their daily lives. Model-eliciting activities (MEAs) were developed to fulfil this need and are very capable of serving this purpose. The reason MEAs are so…

Gender differences in flashbulb memories elicited by the Clarence Thomas hearings.

PubMed

Morse, C K; Woodward, E M; Zweigenhaft, R L

1993-08-01

American students and other adults aged 19-75 completed a questionnaire about flashbulb memories and recollections of autobiographical events elicited by the Senate hearings for confirmation of Clarence Thomas as a Supreme Court Justice. The respondents were less likely to recall vivid image memories than were respondents in earlier studies about memories of the assassinations of John Kennedy, Robert Kennedy, and Martin Luther King. Women were significantly more likely than men to report vivid image memories and recall of autobiographical events elicited by the hearings, but they did not differ significantly from men in the ratings of these memories. Women were also significantly more likely than men to report specific memories of having been victims of sexual harassment and abuse. Women recalled reconsidering incidents in which they might have been victims of sexual harassment more often than men did. Exposure to media coverage did not differ by gender, although the amount of coverage paid attention to did correlate with the number of personal memories elicited.

Elicitation of anti-viral cytotoxic T lymphocytes with purified viral and H-2 antigens.

PubMed

Hale, A H; Ruebush, M J; Harris, D T

1980-07-01

The minimal molecular requirements for elicitation of secondary anti-Sendai virus CTL were investigated. The hemagglutinin-neuraminidase (HN) glycoprotein of Sendai virus and the H-2Kk glycoprotein of YAC tumor cells were purified and incorporated into phospholipid vesicles. These unilamellar liposomes were then tested for the ability to elicit H-2 restricted secondary anti-Sendai virus CTL. The results indicate that these well-defined vesicles were capable of eliciting secondary anti-Sendai virus CTL which lysed only target cells possessing the H-2Kk haplotype and modified with inactivated Sendai virus.

Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning

PubMed Central

Fakhro, Khalid A.; Choi, Murim; Ware, Stephanie M.; Belmont, John W.; Towbin, Jeffrey A.; Lifton, Richard P.; Khokha, Mustafa K.; Brueckner, Martina

2011-01-01

Dominant human genetic diseases that impair reproductive fitness and have high locus heterogeneity constitute a problem for gene discovery because the usual criterion of finding more mutations in specific genes than expected by chance may require extremely large populations. Heterotaxy (Htx), a congenital heart disease resulting from abnormalities in left-right (LR) body patterning, has features suggesting that many cases fall into this category. In this setting, appropriate model systems may provide a means to support implication of specific genes. By high-resolution genotyping of 262 Htx subjects and 991 controls, we identify a twofold excess of subjects with rare genic copy number variations in Htx (14.5% vs. 7.4%, P = 1.5 × 10−4). Although 7 of 45 Htx copy number variations were large chromosomal abnormalities, 38 smaller copy number variations altered a total of 61 genes, 22 of which had Xenopus orthologs. In situ hybridization identified 7 of these 22 genes with expression in the ciliated LR organizer (gastrocoel roof plate), a marked enrichment compared with 40 of 845 previously studied genes (sevenfold enrichment, P < 10−6). Morpholino knockdown in Xenopus of Htx candidates demonstrated that five (NEK2, ROCK2, TGFBR2, GALNT11, and NUP188) strongly disrupted both morphological LR development and expression of pitx2, a molecular marker of LR patterning. These effects were specific, because 0 of 13 control genes from rare Htx or control copy number variations produced significant LR abnormalities (P = 0.001). These findings identify genes not previously implicated in LR patterning. PMID:21282601

Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning.

PubMed

Fakhro, Khalid A; Choi, Murim; Ware, Stephanie M; Belmont, John W; Towbin, Jeffrey A; Lifton, Richard P; Khokha, Mustafa K; Brueckner, Martina

2011-02-15

Dominant human genetic diseases that impair reproductive fitness and have high locus heterogeneity constitute a problem for gene discovery because the usual criterion of finding more mutations in specific genes than expected by chance may require extremely large populations. Heterotaxy (Htx), a congenital heart disease resulting from abnormalities in left-right (LR) body patterning, has features suggesting that many cases fall into this category. In this setting, appropriate model systems may provide a means to support implication of specific genes. By high-resolution genotyping of 262 Htx subjects and 991 controls, we identify a twofold excess of subjects with rare genic copy number variations in Htx (14.5% vs. 7.4%, P = 1.5 × 10(-4)). Although 7 of 45 Htx copy number variations were large chromosomal abnormalities, 38 smaller copy number variations altered a total of 61 genes, 22 of which had Xenopus orthologs. In situ hybridization identified 7 of these 22 genes with expression in the ciliated LR organizer (gastrocoel roof plate), a marked enrichment compared with 40 of 845 previously studied genes (sevenfold enrichment, P < 10(-6)). Morpholino knockdown in Xenopus of Htx candidates demonstrated that five (NEK2, ROCK2, TGFBR2, GALNT11, and NUP188) strongly disrupted both morphological LR development and expression of pitx2, a molecular marker of LR patterning. These effects were specific, because 0 of 13 control genes from rare Htx or control copy number variations produced significant LR abnormalities (P = 0.001). These findings identify genes not previously implicated in LR patterning.

Microarray analysis of differential gene expression elicited in Trametes versicolor during interspecific mycelial interactions.

PubMed

Eyre, Catherine; Muftah, Wafa; Hiscox, Jennifer; Hunt, Julie; Kille, Peter; Boddy, Lynne; Rogers, Hilary J

2010-08-01

Trametes versicolor is an important white rot fungus of both industrial and ecological interest. Saprotrophic basidiomycetes are the major decomposition agents in woodland ecosystems, and rarely form monospecific populations, therefore interspecific mycelial interactions continually occur. Interactions have different outcomes including replacement of one species by the other or deadlock. We have made subtractive cDNA libraries to enrich for genes that are expressed when T. versicolor interacts with another saprotrophic basidiomycete, Stereum gausapatum, an interaction that results in the replacement of the latter. Expressed sequence tags (ESTs) (1920) were used for microarray analysis, and their expression compared during interaction with three different fungi: S. gausapatum (replaced by T. versicolor), Bjerkandera adusta (deadlock) and Hypholoma fasciculare (replaced T. versicolor). Expression of significantly more probes changed in the interaction between T. versicolor and S. gausapatum or B. adusta compared to H. fasciculare, suggesting a relationship between interaction outcome and changes in gene expression. Copyright © 2010 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

BDNF overexpression prevents cognitive deficit elicited by adolescent cannabis exposure and host susceptibility interaction.

PubMed

Segal-Gavish, Hadar; Gazit, Neta; Barhum, Yael; Ben-Zur, Tali; Taler, Michal; Hornfeld, Shay Henry; Gil-Ad, Irit; Weizman, Abraham; Slutsky, Inna; Niwa, Minae; Kamiya, Atsushi; Sawa, Akira; Offen, Daniel; Barzilay, Ran

2017-07-01

Cannabis abuse in adolescence is associated with increased risk of psychotic disorders. Δ-9-tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis. Disrupted-In-Schizophrenia-1 (DISC1) protein is a driver for major mental illness by influencing neurodevelopmental processes. Here, utilizing a unique mouse model based on host (DISC1) X environment (THC administration) interaction, we aimed at studying the pathobiological basis through which THC exposure elicits psychiatric manifestations. Wild-Type and dominant-negative-DISC1 (DN-DISC1) mice were injected with THC (10 mg/kg) or vehicle for 10 days during mid-adolescence-equivalent period. Behavioral tests were conducted to assess exploratory activity (open field test, light-dark box test) and cognitive function (novel object recognition test). Electrophysiological effect of THC was evaluated using acute hippocampal slices, and hippocampal cannabinoid receptor type 1 and brain-derived neurotrophic factor (BDNF) protein levels were measured. Our results indicate that THC exposure elicits deficits in exploratory activity and recognition memory, together with reduced short-term synaptic facilitation and loss of BDNF surge in the hippocampus of DN-DISC mice, but not in wild-type mice. Over-expression of BDNF in the hippocampus of THC-treated DN-DISC1 mice prevented the impairment in recognition memory. The results of this study imply that induction of BDNF following adolescence THC exposure may serve as a homeostatic response geared to maintain proper cognitive function against exogenous insult. The BDNF surge in response to THC is perturbed in the presence of mutant DISC1, suggesting DISC1 may be a useful probe to identify biological cascades involved in the neurochemical, electrophysiological, and behavioral effects of cannabis related psychiatric manifestations. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Elicitation Interview Technique: Capturing People's Experiences of Data Representations.

PubMed

Hogan, Trevor; Hinrichs, Uta; Hornecker, Eva

2016-12-01

Information visualization has become a popular tool to facilitate sense-making, discovery and communication in a large range of professional and casual contexts. However, evaluating visualizations is still a challenge. In particular, we lack techniques to help understand how visualizations are experienced by people. In this paper we discuss the potential of the Elicitation Interview technique to be applied in the context of visualization. The Elicitation Interview is a method for gathering detailed and precise accounts of human experience. We argue that it can be applied to help understand how people experience and interpret visualizations as part of exploration and data analysis processes. We describe the key characteristics of this interview technique and present a study we conducted to exemplify how it can be applied to evaluate data representations. Our study illustrates the types of insights this technique can bring to the fore, for example, evidence for deep interpretation of visual representations and the formation of interpretations and stories beyond the represented data. We discuss general visualization evaluation scenarios where the Elicitation Interview technique may be beneficial and specify what needs to be considered when applying this technique in a visualization context specifically.

A unique amino acid substitution, T126I, in human genotype C of hepatitis B virus S gene and its possible influence on antigenic structural change.

PubMed

Ren, Fengrong; Tsubota, Asahito; Hirokawa, Takatsugu; Kumada, Hiromitsu; Yang, Ziheng; Tanaka, Hiroshi

2006-11-15

Amino acid substitutions in the S gene of hepatitis B virus (HBV), especially in the 'a' determinant region, have been suggested to affect the antigenicity of the virus and the clinical outcome of the infected patient. However, no convincing evidence has been presented for this hypothesis, partly because the 3D structure of the S protein has not been determined. Comparative analysis of viral genes offers an approach to testing this hypothesis, as it may reveal signals of natural selection and provide insights into the functional significance of the observed amino acid substitutions. In this study, we analyze HBV S gene sequences obtained from 24 patients infected with HBV genotypes B or C, together with 16 representative viral strains of HBV genotypes A-F retrieved from GenBank. We use phylogenetic methods to infer evolutionary changes among HBV genotypes and to identify amino acid residues potentially under positive selective pressure. Furthermore, we employ the fragment assembly method to predict structural changes in the S protein. The results showed that an amino acid substitution within the 'a' determinant, T126I, was unique to genotype C, may affect the antigenicity of the HBsAg, and may result in poorer clinical outcomes of patients infected with genotype C viral strains. We suggest that an integrated approach of evolutionary comparison and structural prediction is useful in generating hypotheses for further laboratory validation.

Transposon Variants and Their Effects on Gene Expression in Arabidopsis

PubMed Central

Wang, Xi; Weigel, Detlef; Smith, Lisa M.

2013-01-01

Transposable elements (TEs) make up the majority of many plant genomes. Their transcription and transposition is controlled through siRNAs and epigenetic marks including DNA methylation. To dissect the interplay of siRNA–mediated regulation and TE evolution, and to examine how TE differences affect nearby gene expression, we investigated genome-wide differences in TEs, siRNAs, and gene expression among three Arabidopsis thaliana accessions. Both TE sequence polymorphisms and presence of linked TEs are positively correlated with intraspecific variation in gene expression. The expression of genes within 2 kb of conserved TEs is more stable than that of genes next to variant TEs harboring sequence polymorphisms. Polymorphism levels of TEs and closely linked adjacent genes are positively correlated as well. We also investigated the distribution of 24-nt-long siRNAs, which mediate TE repression. TEs targeted by uniquely mapping siRNAs are on average farther from coding genes, apparently because they more strongly suppress expression of adjacent genes. Furthermore, siRNAs, and especially uniquely mapping siRNAs, are enriched in TE regions missing in other accessions. Thus, targeting by uniquely mapping siRNAs appears to promote sequence deletions in TEs. Overall, our work indicates that siRNA–targeting of TEs may influence removal of sequences from the genome and hence evolution of gene expression in plants. PMID:23408902

Translation elicits a growth rate-dependent, genome-wide, differential protein production in Bacillus subtilis.

PubMed

Borkowski, Olivier; Goelzer, Anne; Schaffer, Marc; Calabre, Magali; Mäder, Ulrike; Aymerich, Stéphane; Jules, Matthieu; Fromion, Vincent

2016-05-17

Complex regulatory programs control cell adaptation to environmental changes by setting condition-specific proteomes. In balanced growth, bacterial protein abundances depend on the dilution rate, transcript abundances and transcript-specific translation efficiencies. We revisited the current theory claiming the invariance of bacterial translation efficiency. By integrating genome-wide transcriptome datasets and datasets from a library of synthetic gfp-reporter fusions, we demonstrated that translation efficiencies in Bacillus subtilis decreased up to fourfold from slow to fast growth. The translation initiation regions elicited a growth rate-dependent, differential production of proteins without regulators, hence revealing a unique, hard-coded, growth rate-dependent mode of regulation. We combined model-based data analyses of transcript and protein abundances genome-wide and revealed that this global regulation is extensively used in B. subtilis We eventually developed a knowledge-based, three-step translation initiation model, experimentally challenged the model predictions and proposed that a growth rate-dependent drop in free ribosome abundance accounted for the differential protein production. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Biologically inspired robots elicit a robust fear response in zebrafish

NASA Astrophysics Data System (ADS)

Ladu, Fabrizio; Bartolini, Tiziana; Panitz, Sarah G.; Butail, Sachit; Macrı, Simone; Porfiri, Maurizio

2015-03-01

We investigate the behavioral response of zebrafish to three fear-evoking stimuli. In a binary choice test, zebrafish are exposed to a live allopatric predator, a biologically-inspired robot, and a computer-animated image of the live predator. A target tracking algorithm is developed to score zebrafish behavior. Unlike computer-animated images, the robotic and live predator elicit a robust avoidance response. Importantly, the robotic stimulus elicits more consistent inter-individual responses than the live predator. Results from this effort are expected to aid in hypothesis-driven studies on zebrafish fear response, by offering a valuable approach to maximize data-throughput and minimize animal subjects.

Induction of phenolic compounds in Hypericum perforatum L. cells by Colletotrichum gloeosporioides elicitation.

PubMed

Conceição, Luis F R; Ferreres, Federico; Tavares, Rui M; Dias, Alberto C P

2006-01-01

Changes in phenolic metabolism after elicitation with Colletotrichum gloeosporioides (CG) has been studied in Hypericum perforatum L. (HP) cell suspension cultures. Soluble phenolics were analysed by HPLC-DAD and HPLC-DAD-MS/MS. HP cultures elicited with the CG elicitor showed a significant increase in xanthone accumulation. Xanthone accumulation increased twelve fold when the cells were primed with methyl-jasmonate (MeJ) or salicylic acid (SA), before elicitation. HP cultures exposed only to MeJ produced a set of flavonoids, the flavones which represent a substantial part (approx. 40%) of the total flavonoids accumulated in these cells. The possible importance of xanthones as a component of defence mechanism of HP against biotic stress is discussed.

Eliciting probabilistic expectations: Collaborations between psychologists and economists

PubMed Central

Bruine de Bruin, Wändi

2017-01-01

We describe two collaborations in which psychologists and economists provided essential support on foundational projects in major research programs. One project involved eliciting adolescents’ expectations regarding significant future life events affecting their psychological and economic development. The second project involved eliciting consumers’ expectations regarding inflation, a potentially vital input to their investment, saving, and purchasing decisions. In each project, we sought questions with the precision needed for economic modeling and the simplicity needed for lay respondents. We identify four conditions that, we believe, promoted our ability to sustain these transdisciplinary collaborations and coproduce the research: (i) having a shared research goal, which neither discipline could achieve on its own; (ii) finding common ground in shared methodology, which met each discipline’s essential evidentiary conditions, but without insisting on its culturally acquired tastes; (iii) sharing the effort throughout, with common language and sense of ownership; and (iv) gaining mutual benefit from both the research process and its products. PMID:28270610

Eliciting probabilistic expectations: Collaborations between psychologists and economists.

PubMed

Bruine de Bruin, Wändi; Fischhoff, Baruch

2017-03-28

We describe two collaborations in which psychologists and economists provided essential support on foundational projects in major research programs. One project involved eliciting adolescents' expectations regarding significant future life events affecting their psychological and economic development. The second project involved eliciting consumers' expectations regarding inflation, a potentially vital input to their investment, saving, and purchasing decisions. In each project, we sought questions with the precision needed for economic modeling and the simplicity needed for lay respondents. We identify four conditions that, we believe, promoted our ability to sustain these transdisciplinary collaborations and coproduce the research: ( i ) having a shared research goal, which neither discipline could achieve on its own; ( ii ) finding common ground in shared methodology, which met each discipline's essential evidentiary conditions, but without insisting on its culturally acquired tastes; ( iii ) sharing the effort throughout, with common language and sense of ownership; and ( iv ) gaining mutual benefit from both the research process and its products.

Gene: a gene-centered information resource at NCBI.

PubMed

Brown, Garth R; Hem, Vichet; Katz, Kenneth S; Ovetsky, Michael; Wallin, Craig; Ermolaeva, Olga; Tolstoy, Igor; Tatusova, Tatiana; Pruitt, Kim D; Maglott, Donna R; Murphy, Terence D

2015-01-01

The National Center for Biotechnology Information's (NCBI) Gene database (www.ncbi.nlm.nih.gov/gene) integrates gene-specific information from multiple data sources. NCBI Reference Sequence (RefSeq) genomes for viruses, prokaryotes and eukaryotes are the primary foundation for Gene records in that they form the critical association between sequence and a tracked gene upon which additional functional and descriptive content is anchored. Additional content is integrated based on the genomic location and RefSeq transcript and protein sequence data. The content of a Gene record represents the integration of curation and automated processing from RefSeq, collaborating model organism databases, consortia such as Gene Ontology, and other databases within NCBI. Records in Gene are assigned unique, tracked integers as identifiers. The content (citations, nomenclature, genomic location, gene products and their attributes, phenotypes, sequences, interactions, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programming utilities (E-Utilities and Entrez Direct) and for bulk transfer by FTP. Published by Oxford University Press on behalf of Nucleic Acids Research 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Conservation demands safe gene drive.

PubMed

Esvelt, Kevin M; Gemmell, Neil J

2017-11-01

Interest in developing gene drive systems to control invasive species is growing, with New Zealand reportedly considering the nascent technology as a way to locally eliminate the mammalian pests that threaten its unique flora and fauna. If gene drives successfully eradicated these invasive populations, many would rejoice, but what are the possible consequences? Here, we explore the risk of accidental spread posed by self-propagating gene drive technologies, highlight new gene drive designs that might achieve better outcomes, and explain why we need open and international discussions concerning a technology that could have global ramifications.

Eliciting Help Without Pity: The Effect of Changing Media Images on Perceptions of Disability.

PubMed

Kamenetsky, Stuart B; Dimakos, Christina; Aslemand, Asal; Saleh, Amani; Ali-Mohammed, Saamiyah

2016-01-01

This study investigated whether newer, more positive disability charity images can elicit helping behavior without producing pity. One hundred sixty-one university undergraduate students were presented with 35 older (1960-1990) and newer (1991-2010) disability charity images and completed a questionnaire about each image. Results indicate that overall, identification with depicted individuals was low; positive attitudes and perceptions of capabilities were moderate to high. Newer images led to more positive responses, but no significant difference in willingness to help. Eliciting pity through negative depictions of disability appears not to be a necessary precondition for eliciting helping behavior toward people with disabilities.

Comparison of elicitation potential of chloroatranol and atranol--2 allergens in oak moss absolute.

PubMed

Johansen, Jeanne D; Bernard, Guillaume; Giménez-Arnau, Elena; Lepoittevin, Jean-Pierre; Bruze, Magnus; Andersen, Klaus E

2006-04-01

Chloroatranol and atranol are degradation products of chloroatranorin and atranorin, respectively, and have recently been identified as important contact allergens in the natural fragrance extract, oak moss absolute. Oak moss absolute is widely used in perfumery and is the cause of many cases of fragrance allergic contact dermatitis. Chloroatranol elicits reactions at very low levels of exposure. In oak moss absolute, chloroatranol and atranol are present together and both may contribute to the allergenicity and eliciting capacity of the natural extract. In this study, 10 eczema patients with known sensitization to chloroatranol and oak moss absolute were tested simultaneously to a serial dilution of chloroatranol and atranol in ethanol, in equimolar concentrations (0.0034-1072 microM). Dose-response curves were estimated and analysed by logistic regression. The estimated difference in elicitation potency of chloroatranol relative to atranol based on testing with equimolar concentrations was 217% (95% confidence interval 116-409%). Both substances elicited reactions at very low levels of exposure. It is concluded that the differences in elicitation capacity between the 2 substances are counterbalanced by exposure being greater to atranol than to chloroatranol and that both substances contribute to the clinical problems seen in oak moss absolute-sensitized individuals.

A Novel Pathogenic Variant in the MITF Gene Segregating with a Unique Spectrum of Ocular Findings in an Extended Iranian Waardenburg Syndrome Kindred

PubMed Central

Jalilian, Nazanin; Tabatabaiefar, Mohammad A.; Bahrami, Tayyeb; Karbasi, Golaleh; Bahramian, Mohammad H.; Salimpoor, Abdolrahman; Noori-Daloii, Mohammad R.

2017-01-01

Waardenburg syndrome (WS) is a rare genetic disorder characterized by abnormal pigmentation of the hair, skin, and iris as well as sensorineural hearing loss. WS is subdivided into 4 major types (WS1–4), where WS2 is characterized by the absence of dystopia canthorum. This study was launched to investigate clinical and molecular characteristics of WS in an extended Iranian WS2 family. A comprehensive clinical investigation was performed. Peripheral blood samples were collected and genomic DNA was extracted. Affected members of the family were studied for possible mutations within the SOX10, MITF, and SNAI2 genes. Six WS2 individuals affected from a large Iranian WS2 kindred were enrolled. All affected members carried the novel substitution c.877C>T at exon 9 in the MITF gene, which resulted in p.Arg293* at the protein level. None of the healthy members and also of 50 ethnically matched controls had this variant. In addition, a spectrum of unique ocular findings, including nystagmus, chorioretinal degeneration, optic disc hypoplasia, astigmatism, and myopia, was segregated with the mutant allele in the pedigree. Our data provide insight into the genotypic and phenotypic spectrum of WS2 in an Iranian family and could further expand the spectrum of MITF mutations and have implications for genetic counseling on WS in Iran. PMID:28690485

A Novel Pathogenic Variant in the MITF Gene Segregating with a Unique Spectrum of Ocular Findings in an Extended Iranian Waardenburg Syndrome Kindred.

PubMed

Jalilian, Nazanin; Tabatabaiefar, Mohammad A; Bahrami, Tayyeb; Karbasi, Golaleh; Bahramian, Mohammad H; Salimpoor, Abdolrahman; Noori-Daloii, Mohammad R

2017-06-01

Waardenburg syndrome (WS) is a rare genetic disorder characterized by abnormal pigmentation of the hair, skin, and iris as well as sensorineural hearing loss. WS is subdivided into 4 major types (WS1-4), where WS2 is characterized by the absence of dystopia canthorum. This study was launched to investigate clinical and molecular characteristics of WS in an extended Iranian WS2 family. A comprehensive clinical investigation was performed. Peripheral blood samples were collected and genomic DNA was extracted. Affected members of the family were studied for possible mutations within the SOX10 , MITF , and SNAI2 genes. Six WS2 individuals affected from a large Iranian WS2 kindred were enrolled. All affected members carried the novel substitution c.877C>T at exon 9 in the MITF gene, which resulted in p.Arg293* at the protein level. None of the healthy members and also of 50 ethnically matched controls had this variant. In addition, a spectrum of unique ocular findings, including nystagmus, chorioretinal degeneration, optic disc hypoplasia, astigmatism, and myopia, was segregated with the mutant allele in the pedigree. Our data provide insight into the genotypic and phenotypic spectrum of WS2 in an Iranian family and could further expand the spectrum of MITF mutations and have implications for genetic counseling on WS in Iran.

Automated interviews on clinical case reports to elicit directed acyclic graphs.

PubMed

Luciani, Davide; Stefanini, Federico M

2012-05-01

Setting up clinical reports within hospital information systems makes it possible to record a variety of clinical presentations. Directed acyclic graphs (Dags) offer a useful way of representing causal relations in clinical problem domains and are at the core of many probabilistic models described in the medical literature, like Bayesian networks. However, medical practitioners are not usually trained to elicit Dag features. Part of the difficulty lies in the application of the concept of direct causality before selecting all the causal variables of interest for a specific patient. We designed an automated interview to tutor medical doctors in the development of Dags to represent their understanding of clinical reports. Medical notions were analyzed to find patterns in medical reasoning that can be followed by algorithms supporting the elicitation of causal Dags. Clinical relevance was defined to help formulate only relevant questions by driving an expert's attention towards variables causally related to nodes already inserted in the graph. Key procedural features of the proposed interview are described by four algorithms. The automated interview comprises questions on medical notions, phrased in medical terms. The first elicitation session produces questions concerning the patient's chief complaints and the outcomes related to diseases serving as diagnostic hypotheses, their observable manifestations and risk factors. The second session focuses on questions that refine the initial causal paths by considering syndromes, dysfunctions, pathogenic anomalies, biases and effect modifiers. A case study concerning a gastro-enterological problem and one dealing with an infected patient illustrate the output produced by the algorithms, depending on the answers provided by the doctor. The proposed elicitation framework is characterized by strong consistency with medical background and by a progressive introduction of relevant medical topics. Revision and testing of the

Silybin content and overexpression of chalcone synthase genes in Silybum marianum L. plants under abiotic elicitation.

PubMed

El-Garhy, Hoda A S; Khattab, Salah; Moustafa, Mahmoud M A; Abou Ali, Rania; Abdel Azeiz, Ahmed Z; Elhalwagi, Abeer; El Sherif, Fadia

2016-11-01

Silymarin, a Silybum marianum seed extract containing a mixture of flavonolignans including silybin, is being used as an antihepatotoxic therapy for liver diseases. In this study, the enhancing effect of gamma irradiation on plant growth parameters of S. marianum under salt stress was investigated. The effect of gamma irradiation, either as a single elicitor or coupled with salinity, on chalcone synthase (CHS) gene expression and silybin A + B yield was also evaluated. The silybin A + B content in S. marianum fruits was estimated by liquid chromatography-mass spectrometry (LC-MS/MS). An increase in silybin content was accompanied by up-regulation of the CHS1, CHS2 and CHS3 genes, which are involved in the silybin biosynthetic pathway. The highest silybin A + B production (0.77 g/100 g plant DW) and transcript levels of the three studied genes (100.2-, 91.9-, and 24.3-fold increase, respectively) were obtained with 100GY gamma irradiation and 4000 ppm salty water. The CHS2 and CHS3 genes were partially sequenced and submitted to the NCBI database under the accession numbers KT252908.1 and KT252909.1, respectively. Developing new approaches to stimulate silybin biosynthetic pathways could be a useful tool to potentiate the use of plants as renewable resources of medicinal compounds. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

An analysis of correspondence between unique rabies virus variants and divergent big brown bat (Eptesicus fuscus) mitochondrial DNA lineages

USGS Publications Warehouse

Neubaum, M.A.; Shankar, V.; Douglas, M.R.; Douglas, M.E.; O'Shea, T.J.; Rupprecht, C.E.

2008-01-01

The literature supports that unique rabies virus (RABV) variants are often compartmentalized in different species of bats. In Colorado, two divergent mtDNA lineages of big brown bats (Eptesicus fuscus) co-occur. RABV associated with this species also segregates into two clades. We hypothesized that unique RABV variants might be associated with mtDNA lineages of Colorado big brown bats. DNA was extracted from brain tissue of rabid big brown bats, the ND2 gene was amplified to determine mtDNA lineage, and the lineage was compared to a previously derived phylogenetic analysis of the RABV N gene. No correspondence was found between host bat lineage and RABV variant. ?? 2008 Springer-Verlag.

Gene recovery microdissection (GRM) a process for producing chromosome region-specific libraries of expressed genes

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

Christian, A T; Coleman, M A; Tucker, J D

2001-02-08

Gene Recovery Microdissection (GRM) is a unique and cost-effective process for producing chromosome region-specific libraries of expressed genes. It accelerates the pace, reduces the cost, and extends the capabilities of functional genomic research, the means by which scientists will put to life-saving, life-enhancing use their knowledge of any plant or animal genome.

Beyond the Central Dogma: Model-Based Learning of How Genes Determine Phenotypes

ERIC Educational Resources Information Center

Reinagel, Adam; Speth, Elena Bray

2016-01-01

In an introductory biology course, we implemented a learner-centered, model-based pedagogy that frequently engaged students in building conceptual models to explain how genes determine phenotypes. Model-building tasks were incorporated within case studies and aimed at eliciting students' understanding of 1) the origin of variation in a population…

Plant Ion Channels: Gene Families, Physiology, and Functional Genomics Analyses

PubMed Central

Ward, John M.; Mäser, Pascal; Schroeder, Julian I.

2016-01-01

Distinct potassium, anion, and calcium channels in the plasma membrane and vacuolar membrane of plant cells have been identified and characterized by patch clamping. Primarily owing to advances in Arabidopsis genetics and genomics, and yeast functional complementation, many of the corresponding genes have been identified. Recent advances in our understanding of ion channel genes that mediate signal transduction and ion transport are discussed here. Some plant ion channels, for example, ALMT and SLAC anion channel subunits, are unique. The majority of plant ion channel families exhibit homology to animal genes; such families include both hyperpolarization-and depolarization-activated Shaker-type potassium channels, CLC chloride transporters/channels, cyclic nucleotide–gated channels, and ionotropic glutamate receptor homologs. These plant ion channels offer unique opportunities to analyze the structural mechanisms and functions of ion channels. Here we review gene families of selected plant ion channel classes and discuss unique structure-function aspects and their physiological roles in plant cell signaling and transport. PMID:18842100

Plant ion channels: gene families, physiology, and functional genomics analyses.

PubMed

Ward, John M; Mäser, Pascal; Schroeder, Julian I

2009-01-01

Distinct potassium, anion, and calcium channels in the plasma membrane and vacuolar membrane of plant cells have been identified and characterized by patch clamping. Primarily owing to advances in Arabidopsis genetics and genomics, and yeast functional complementation, many of the corresponding genes have been identified. Recent advances in our understanding of ion channel genes that mediate signal transduction and ion transport are discussed here. Some plant ion channels, for example, ALMT and SLAC anion channel subunits, are unique. The majority of plant ion channel families exhibit homology to animal genes; such families include both hyperpolarization- and depolarization-activated Shaker-type potassium channels, CLC chloride transporters/channels, cyclic nucleotide-gated channels, and ionotropic glutamate receptor homologs. These plant ion channels offer unique opportunities to analyze the structural mechanisms and functions of ion channels. Here we review gene families of selected plant ion channel classes and discuss unique structure-function aspects and their physiological roles in plant cell signaling and transport.

The unique stem cell system of the immortal larva of the human parasite Echinococcus multilocularis

PubMed Central

2014-01-01

Background It is believed that in tapeworms a separate population of undifferentiated cells, the germinative cells, is the only source of cell proliferation throughout the life cycle (similar to the neoblasts of free living flatworms). In Echinococcus multilocularis, the metacestode larval stage has a unique development, growing continuously like a mass of vesicles that infiltrate the tissues of the intermediate host, generating multiple protoscoleces by asexual budding. This unique proliferation potential indicates the existence of stem cells that are totipotent and have the ability for extensive self-renewal. Results We show that only the germinative cells proliferate in the larval vesicles and in primary cell cultures that undergo complete vesicle regeneration, by using a combination of morphological criteria and by developing molecular markers of differentiated cell types. The germinative cells are homogeneous in morphology but heterogeneous at the molecular level, since only sub-populations express homologs of the post-transcriptional regulators nanos and argonaute. Important differences are observed between the expression patterns of selected neoblast marker genes of other flatworms and the E. multilocularis germinative cells, including widespread expression in E. multilocularis of some genes that are neoblast-specific in planarians. Hydroxyurea treatment results in the depletion of germinative cells in larval vesicles, and after recovery following hydroxyurea treatment, surviving proliferating cells grow as patches that suggest extensive self-renewal potential for individual germinative cells. Conclusions In E. multilocularis metacestodes, the germinative cells are the only proliferating cells, presumably driving the continuous growth of the larval vesicles. However, the existence of sub-populations of the germinative cells is strongly supported by our data. Although the germinative cells are very similar to the neoblasts of other flatworms in function and

The unique stem cell system of the immortal larva of the human parasite Echinococcus multilocularis.

PubMed

Koziol, Uriel; Rauschendorfer, Theresa; Zanon Rodríguez, Luis; Krohne, Georg; Brehm, Klaus

2014-03-06

It is believed that in tapeworms a separate population of undifferentiated cells, the germinative cells, is the only source of cell proliferation throughout the life cycle (similar to the neoblasts of free living flatworms). In Echinococcus multilocularis, the metacestode larval stage has a unique development, growing continuously like a mass of vesicles that infiltrate the tissues of the intermediate host, generating multiple protoscoleces by asexual budding. This unique proliferation potential indicates the existence of stem cells that are totipotent and have the ability for extensive self-renewal. We show that only the germinative cells proliferate in the larval vesicles and in primary cell cultures that undergo complete vesicle regeneration, by using a combination of morphological criteria and by developing molecular markers of differentiated cell types. The germinative cells are homogeneous in morphology but heterogeneous at the molecular level, since only sub-populations express homologs of the post-transcriptional regulators nanos and argonaute. Important differences are observed between the expression patterns of selected neoblast marker genes of other flatworms and the E. multilocularis germinative cells, including widespread expression in E. multilocularis of some genes that are neoblast-specific in planarians. Hydroxyurea treatment results in the depletion of germinative cells in larval vesicles, and after recovery following hydroxyurea treatment, surviving proliferating cells grow as patches that suggest extensive self-renewal potential for individual germinative cells. In E. multilocularis metacestodes, the germinative cells are the only proliferating cells, presumably driving the continuous growth of the larval vesicles. However, the existence of sub-populations of the germinative cells is strongly supported by our data. Although the germinative cells are very similar to the neoblasts of other flatworms in function and in undifferentiated morphology

Core and Shell Song Systems Unique to the Parrot Brain

PubMed Central

Chakraborty, Mukta; Walløe, Solveig; Nedergaard, Signe; Fridel, Emma E.; Dabelsteen, Torben; Pakkenberg, Bente; Bertelsen, Mads F.; Dorrestein, Gerry M.; Brauth, Steven E.; Durand, Sarah E.; Jarvis, Erich D.

2015-01-01

The ability to imitate complex sounds is rare, and among birds has been found only in parrots, songbirds, and hummingbirds. Parrots exhibit the most advanced vocal mimicry among non-human animals. A few studies have noted differences in connectivity, brain position and shape in the vocal learning systems of parrots relative to songbirds and hummingbirds. However, only one parrot species, the budgerigar, has been examined and no differences in the presence of song system structures were found with other avian vocal learners. Motivated by questions of whether there are important differences in the vocal systems of parrots relative to other vocal learners, we used specialized constitutive gene expression, singing-driven gene expression, and neural connectivity tracing experiments to further characterize the song system of budgerigars and/or other parrots. We found that the parrot brain uniquely contains a song system within a song system. The parrot “core” song system is similar to the song systems of songbirds and hummingbirds, whereas the “shell” song system is unique to parrots. The core with only rudimentary shell regions were found in the New Zealand kea, representing one of the only living species at a basal divergence with all other parrots, implying that parrots evolved vocal learning systems at least 29 million years ago. Relative size differences in the core and shell regions occur among species, which we suggest could be related to species differences in vocal and cognitive abilities. PMID:26107173

The gene space in wheat: the complete γ-gliadin gene family from the wheat cultivar Chinese Spring.

PubMed

Anderson, Olin D; Huo, Naxin; Gu, Yong Q

2013-06-01

The complete set of unique γ-gliadin genes is described for the wheat cultivar Chinese Spring using a combination of expressed sequence tag (EST) and Roche 454 DNA sequences. Assemblies of Chinese Spring ESTs yielded 11 different γ-gliadin gene sequences. Two of the sequences encode identical polypeptides and are assumed to be the result of a recent gene duplication. One gene has a 3' coding mutation that changes the reading frame in the final eight codons. A second assembly of Chinese Spring γ-gliadin sequences was generated using Roche 454 total genomic DNA sequences. The 454 assembly confirmed the same 11 active genes as the EST assembly plus two pseudogenes not represented by ESTs. These 13 γ-gliadin sequences represent the complete unique set of γ-gliadin genes for cv Chinese Spring, although not ruled out are additional genes that are exact duplications of these 13 genes. A comparison with the ESTs of two other hexaploid cultivars (Butte 86 and Recital) finds that the most active genes are present in all three cultivars, with exceptions likely due to too few ESTs for detection in Butte 86 and Recital. A comparison of the numbers of ESTs per gene indicates differential levels of expression within the γ-gliadin gene family. Genome assignments were made for 6 of the 13 Chinese Spring γ-gliadin genes, i.e., one assignment from a match to two γ-gliadin genes found within a tetraploid wheat A genome BAC and four genes that match four distinct γ-gliadin sequences assembled from Roche 454 sequences from Aegilops tauschii, the hexaploid wheat D-genome ancestor.

Action potential bursts in central snail neurons elicited by paeonol: roles of ionic currents

PubMed Central

Chen, Yi-hung; Lin, Pei-lin; Hsu, Hui-yu; Wu, Ya-ting; Yang, Han-yin; Lu, Dah-yuu; Huang, Shiang-suo; Hsieh, Ching-liang; Lin, Jaung-geng

2010-01-01

Aim: To investigate the effects of 2′-hydroxy-4′-methoxyacetophenone (paeonol) on the electrophysiological behavior of a central neuron (right parietal 4; RP4) of the giant African snail (Achatina fulica Ferussac). Methods: Intracellular recordings and the two-electrode voltage clamp method were used to study the effects of paeonol on the RP4 neuron. Results: The RP4 neuron generated spontaneous action potentials. Bath application of paeonol at a concentration of ≥500 μmol/L reversibly elicited action potential bursts in a concentration-dependent manner. Immersing the neurons in Co2+-substituted Ca2+-free solution did not block paeonol-elicited bursting. Pretreatment with the protein kinase A (PKA) inhibitor KT-5720 or the protein kinase C (PKC) inhibitor Ro 31-8220 did not affect the action potential bursts. Voltage-clamp studies revealed that paeonol at a concentration of 500 μmol/L had no remarkable effects on the total inward currents, whereas paeonol decreased the delayed rectifying K+ current (IKD) and the fast-inactivating K+ current (IA). Application of 4-aminopyridine (4-AP 5 mmol/L), an inhibitor of IA, or charybdotoxin 250 nmol/L, an inhibitor of the Ca2+-activated K+ current (IK(Ca)), failed to elicit action potential bursts, whereas tetraethylammonium chloride (TEA 50 mmol/L), an IKD blocker, successfully elicited action potential bursts. At a lower concentration of 5 mmol/L, TEA facilitated the induction of action potential bursts elicited by paeonol. Conclusion: Paeonol elicited a bursting firing pattern of action potentials in the RP4 neuron and this activity relates closely to the inhibitory effects of paeonol on the IKD. PMID:21042287

Conditioned responses elicited by experimentally produced cues for smoking.

PubMed

Mucha, R F; Pauli, P; Angrilli, A

1998-03-01

Several theories of drug-craving postulate that a signal for drug elicits conditioned responses. However, depending on the theory, a drug cue is said to elicit drug similar, drug compensatory, positive motivational, and negative motivational effects. Since animal data alone cannot tease apart the relative importance of different cue-related processes in the addict, we developed and examined a model of drug cues in the human based on a two-sound, differential conditioning procedure using smoking as the reinforcer. After multiple pairings of a sound with smoking, there was a preference for the smoking cue on a conditioned preference test. The acute effects of smoking (increased heart rate, respiration rate, skin conductance level, skin conductance fluctuations, EEG beta power and trapezius EMG, decreased alpha power) were not affected by the smoking cue, although subjects drew more on their cigarette in the presence of the smoking cue than in the presence of a control cue. Moreover, the cue did not change baseline behaviour except for a possible increase in EEG beta power and an increase in trapezius EMG at about the time when smoking should have occurred. The findings confirm the value of experimental models of drug cues in the human for comparing different cue phenomena in the dependent individual. They indicate that an acquired signal for drug in the human may elicit incentive motivational effects and associated preparatory motor responses in addition to possible conditioned tolerance.

Stimulus-Elicited Connectivity Influences Resting-State Connectivity Years Later in Human Development: A Prospective Study.

PubMed

Gabard-Durnam, Laurel Joy; Gee, Dylan Grace; Goff, Bonnie; Flannery, Jessica; Telzer, Eva; Humphreys, Kathryn Leigh; Lumian, Daniel Stephen; Fareri, Dominic Stephen; Caldera, Christina; Tottenham, Nim

2016-04-27

Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is currently known about the mechanisms through which these networks assemble into stable mature patterns. The current study posits and tests the long-term phasic molding hypothesis that resting-state networks are gradually shaped by recurring stimulus-elicited connectivity across development by examining how both stimulus-elicited and resting-state functional connections of the human brain emerge over development at the systems level. Using a sequential design following 4- to 18-year-olds over a 2 year period, we examined the predictive associations between stimulus-elicited and resting-state connectivity in amygdala-cortical circuitry as an exemplar case (given this network's protracted development across these ages). Age-related changes in amygdala functional connectivity converged on the same regions of medial prefrontal cortex (mPFC) and inferior frontal gyrus when elicited by emotional stimuli and when measured at rest. Consistent with the long-term phasic molding hypothesis, prospective analyses for both connections showed that the magnitude of an individual's stimulus-elicited connectivity unidirectionally predicted resting-state functional connectivity 2 years later. For the amygdala-mPFC connection, only stimulus-elicited connectivity during childhood and the transition to adolescence shaped future resting-state connectivity, consistent with a sensitive period ending with adolescence for the amygdala-mPFC circuit. Together, these findings suggest that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited by environmental stimuli over the course of development on the order of years. A fundamental issue in understanding the ontogeny of brain function is how resting-state (intrinsic) functional networks emerge and relate to stimulus-elicited functional connectivity. Here, we posit and test the long

Stimulus-Elicited Connectivity Influences Resting-State Connectivity Years Later in Human Development: A Prospective Study

PubMed Central

Gee, Dylan Grace; Goff, Bonnie; Flannery, Jessica; Telzer, Eva; Humphreys, Kathryn Leigh; Lumian, Daniel Stephen; Fareri, Dominic Stephen; Caldera, Christina; Tottenham, Nim

2016-01-01

Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is currently known about the mechanisms through which these networks assemble into stable mature patterns. The current study posits and tests the long-term phasic molding hypothesis that resting-state networks are gradually shaped by recurring stimulus-elicited connectivity across development by examining how both stimulus-elicited and resting-state functional connections of the human brain emerge over development at the systems level. Using a sequential design following 4- to 18-year-olds over a 2 year period, we examined the predictive associations between stimulus-elicited and resting-state connectivity in amygdala-cortical circuitry as an exemplar case (given this network's protracted development across these ages). Age-related changes in amygdala functional connectivity converged on the same regions of medial prefrontal cortex (mPFC) and inferior frontal gyrus when elicited by emotional stimuli and when measured at rest. Consistent with the long-term phasic molding hypothesis, prospective analyses for both connections showed that the magnitude of an individual's stimulus-elicited connectivity unidirectionally predicted resting-state functional connectivity 2 years later. For the amygdala-mPFC connection, only stimulus-elicited connectivity during childhood and the transition to adolescence shaped future resting-state connectivity, consistent with a sensitive period ending with adolescence for the amygdala-mPFC circuit. Together, these findings suggest that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited by environmental stimuli over the course of development on the order of years. SIGNIFICANCE STATEMENT A fundamental issue in understanding the ontogeny of brain function is how resting-state (intrinsic) functional networks emerge and relate to stimulus-elicited functional connectivity. Here, we

Elicitation of macrophages from the peritoneal cavity of channel catfish

USGS Publications Warehouse

Jenkins, J.A.; Klesius, P.H.

1998-01-01

Four chemicals were evaluated for elicitation of macrophages in peritoneal cavities of 250-300g healthy channel catfish Ictalurus punctatus. Cellular exudates were collected at 3, 5, 7, 10, 14, and 20 d following intraperitoneal injections with squalene, Freund's incomplete adjuvant (FIA), goat serum, thioglycollate, or as a control, phosphate-buffered saline. Injection with either squalene or FIA induced significantly greater (P ??? 0.0001) macrophage recruitment than the other chemicals. The effectiveness of squalene and FIA was compared further by macrophage collection daily for 7 d. Squalene and FIA elicited similarly high macrophage responses (P ??? 0.0450), the highest being 3.43 x 106 macrophages/mL (SE, 2.4 x l06) at 99% purity at day 2 and 2.1 X 106 macrophages/mL (SE, 0.7 x 106) at day 14 at 80% purity, respectively. In both experiments, the time after injection was not statistically significant, nor was there an interaction between time and chemicals. The occurrence of cells other than macrophages decreased with time to yield macrophage recoveries of 47-99% for squalene and 30-80% for FIA. Two subsets of macrophages were observed by means of flow cytometry. As demonstrated by chemiluminescence, the squalene-elicited cells produced high-energy oxygen compounds important to the phagocytic process.

[Uniqueness seeking behavior as a self-verification: an alternative approach to the study of uniqueness].

PubMed

Yamaoka, S

1995-06-01

Uniqueness theory explains that extremely high perceived similarity between self and others evokes negative emotional reactions and causes uniqueness seeking behavior. However, the theory conceptualizes similarity so ambiguously that it appears to suffer from low predictive validity. The purpose of the current article is to propose an alternative explanation of uniqueness seeking behavior. It posits that perceived uniqueness deprivation is a threat to self-concepts, and therefore causes self-verification behavior. Two levels of self verification are conceived: one based on personal categorization and the other on social categorization. The present approach regards uniqueness seeking behavior as the personal-level self verification. To test these propositions, a 2 (very high or moderate similarity information) x 2 (with or without outgroup information) x 2 (high or low need for uniqueness) between-subject factorial-design experiment was conducted with 95 university students. Results supported the self-verification approach, and were discussed in terms of effects of uniqueness deprivation, levels of self-categorization, and individual differences in need for uniqueness.

Use (and abuse) of expert elicitation in support of decision making for public policy

PubMed Central

Morgan, M. Granger

2014-01-01

The elicitation of scientific and technical judgments from experts, in the form of subjective probability distributions, can be a valuable addition to other forms of evidence in support of public policy decision making. This paper explores when it is sensible to perform such elicitation and how that can best be done. A number of key issues are discussed, including topics on which there are, and are not, experts who have knowledge that provides a basis for making informed predictive judgments; the inadequacy of only using qualitative uncertainty language; the role of cognitive heuristics and of overconfidence; the choice of experts; the development, refinement, and iterative testing of elicitation protocols that are designed to help experts to consider systematically all relevant knowledge when they make their judgments; the treatment of uncertainty about model functional form; diversity of expert opinion; and when it does or does not make sense to combine judgments from different experts. Although it may be tempting to view expert elicitation as a low-cost, low-effort alternative to conducting serious research and analysis, it is neither. Rather, expert elicitation should build on and use the best available research and analysis and be undertaken only when, given those, the state of knowledge will remain insufficient to support timely informed assessment and decision making. PMID:24821779

Radiation-induced gene expression in the nematode Caenorhabditis elegans

NASA Technical Reports Server (NTRS)

Nelson, Gregory A.; Jones, Tamako A.; Chesnut, Aaron; Smith, Anna L.

2002-01-01

We used the nematode C. elegans to characterize the genotoxic and cytotoxic effects of ionizing radiation in a simple animal model emphasizing the unique effects of charged particle radiation. Here we demonstrate by RT-PCR differential display and whole genome microarray hybridization experiments that gamma rays, accelerated protons and iron ions at the same physical dose lead to unique transcription profiles. 599 of 17871 genes analyzed (3.4%) showed differential expression 3 hrs after exposure to 3 Gy of radiation. 193 were up-regulated, 406 were down-regulated and 90% were affected only by a single species of radiation. A novel statistical clustering technique identified the regulatory relationships between the radiation-modulated genes and showed that genes affected by each radiation species were associated with unique regulatory clusters. This suggests that independent homeostatic mechanisms are activated in response to radiation exposure as a function of track structure or ionization density.

Engaging Young Children in Research through Photo Elicitation

ERIC Educational Resources Information Center

Pyle, Angela

2013-01-01

Embracing the new sociology of childhood, this paper describes a participatory research method built on a belief in the competency of young children. The paper begins with a critical review of the photo elicitation literature exploring the varied levels of children's participation. Drawing on the strengths of the previous research, a multi-step…

N400 elicited by incongruent ending words of Chinese idioms in healthy adults.

PubMed

Chen, Xing-shi; Tang, Yun-xiang; Xiao, Ze-ping; Wang, Ji-jun; Zhang, Ming-dao; Zhang, Zai-fu; Hu, Zhen-yu; Lou, Fei-ying; Chen, Chong; Zhang, Tian-hong

2010-03-20

Prior research about N400 has been mainly based on English stimuli, while the cognitive processing of Chinese characters is still unclear. The aim of the present study was to further investigate the semantic processing of Chinese idioms. Event related potentials (ERP) component N400 was elicited by 38 pairs of matching (congruent) and mismatching (incongruent) ended Chinese idioms: ending words with same phoneme but different shape and meaning (sPdSdM), with similar shape but different phoneme and meaning (sSdPdM), with same meaning but different phoneme and shape (sMdPdS), and words with different phoneme, shape and meaning (dPdSdM) and recorded by Guangzhou Runjie WJ-1 ERP instruments. In 62 right-handed healthy adults (age 19 - 50 years), N400 amplitudes and latencies were compared between matching and mismatching conditions at Fz, Cz and Pz. N400 showed a midline distribution and could be elicited in electrodes Fz, Cz and Pz. The mean values of N400 latencies and amplitudes were obtained for matching and mismatching ending words in healthy adults. Significant differences were found in N400 latencies and amplitudes in matching and mismatching ending-words idioms in healthy adults (P < 0.05). Compared with matching ending-words idioms, N400 latencies were prolonged and the amplitudes were increased in mismatching ones. N400s elicited by different types of stimuli showed different latencies and amplitudes, and longest N400 latency and largest N400 amplitude were elicited by ending-words with dPdSdM. No gender difference was found of N400 latency and amplitude in this study (P > 0.05). Compared with English stimuli, Chinese ideographic words could provide more flexible stimuli for N400 research in that the words have 3-dimension changes - phoneme, shape and meaning. Features of N400 elicited by matching and mismatching ending words in Chinese idioms are mainly determined by the meaning of the word. Some issues of N400 elicited by Chinese characters deserve further

Whipworm kinomes reflect a unique biology and adaptation to the host animal.

PubMed

Stroehlein, Andreas J; Young, Neil D; Korhonen, Pasi K; Chang, Bill C H; Nejsum, Peter; Pozio, Edoardo; La Rosa, Giuseppe; Sternberg, Paul W; Gasser, Robin B

2017-11-01

Roundworms belong to a diverse phylum (Nematoda) which is comprised of many parasitic species including whipworms (genus Trichuris). These worms have adapted to a biological niche within the host and exhibit unique morphological characteristics compared with other nematodes. Although these adaptations are known, the underlying molecular mechanisms remain elusive. The availability of genomes and transcriptomes of some whipworms now enables detailed studies of their molecular biology. Here, we defined and curated the full complement of an important class of enzymes, the protein kinases (kinomes) of two species of Trichuris, using an advanced and integrated bioinformatic pipeline. We investigated the transcription of Trichuris suis kinase genes across developmental stages, sexes and tissues, and reveal that selectively transcribed genes can be linked to central roles in developmental and reproductive processes. We also classified and functionally annotated the curated kinomes by integrating evidence from structural modelling and pathway analyses, and compared them with other curated kinomes of phylogenetically diverse nematode species. Our findings suggest unique adaptations in signalling processes governing worm morphology and biology, and provide an important resource that should facilitate experimental investigations of kinases and the biology of signalling pathways in nematodes. Copyright © 2017 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Target gene analysis by microarrays and chromatin immunoprecipitation identifies HEY proteins as highly redundant bHLH repressors.

PubMed

Heisig, Julia; Weber, David; Englberger, Eva; Winkler, Anja; Kneitz, Susanne; Sung, Wing-Kin; Wolf, Elmar; Eilers, Martin; Wei, Chia-Lin; Gessler, Manfred

2012-01-01

HEY bHLH transcription factors have been shown to regulate multiple key steps in cardiovascular development. They can be induced by activated NOTCH receptors, but other upstream stimuli mediated by TGFß and BMP receptors may elicit a similar response. While the basic and helix-loop-helix domains exhibit strong similarity, large parts of the proteins are still unique and may serve divergent functions. The striking overlap of cardiac defects in HEY2 and combined HEY1/HEYL knockout mice suggested that all three HEY genes fulfill overlapping function in target cells. We therefore sought to identify target genes for HEY proteins by microarray expression and ChIPseq analyses in HEK293 cells, cardiomyocytes, and murine hearts. HEY proteins were found to modulate expression of their target gene to a rather limited extent, but with striking functional interchangeability between HEY factors. Chromatin immunoprecipitation revealed a much greater number of potential binding sites that again largely overlap between HEY factors. Binding sites are clustered in the proximal promoter region especially of transcriptional regulators or developmental control genes. Multiple lines of evidence suggest that HEY proteins primarily act as direct transcriptional repressors, while gene activation seems to be due to secondary or indirect effects. Mutagenesis of putative DNA binding residues supports the notion of direct DNA binding. While class B E-box sequences (CACGYG) clearly represent preferred target sequences, there must be additional and more loosely defined modes of DNA binding since many of the target promoters that are efficiently bound by HEY proteins do not contain an E-box motif. These data clearly establish the three HEY bHLH factors as highly redundant transcriptional repressors in vitro and in vivo, which explains the combinatorial action observed in different tissues with overlapping expression.

Target Gene Analysis by Microarrays and Chromatin Immunoprecipitation Identifies HEY Proteins as Highly Redundant bHLH Repressors

PubMed Central

Englberger, Eva; Winkler, Anja; Kneitz, Susanne; Sung, Wing-Kin; Wolf, Elmar; Eilers, Martin; Wei, Chia-Lin; Gessler, Manfred

2012-01-01

HEY bHLH transcription factors have been shown to regulate multiple key steps in cardiovascular development. They can be induced by activated NOTCH receptors, but other upstream stimuli mediated by TGFß and BMP receptors may elicit a similar response. While the basic and helix-loop-helix domains exhibit strong similarity, large parts of the proteins are still unique and may serve divergent functions. The striking overlap of cardiac defects in HEY2 and combined HEY1/HEYL knockout mice suggested that all three HEY genes fulfill overlapping function in target cells. We therefore sought to identify target genes for HEY proteins by microarray expression and ChIPseq analyses in HEK293 cells, cardiomyocytes, and murine hearts. HEY proteins were found to modulate expression of their target gene to a rather limited extent, but with striking functional interchangeability between HEY factors. Chromatin immunoprecipitation revealed a much greater number of potential binding sites that again largely overlap between HEY factors. Binding sites are clustered in the proximal promoter region especially of transcriptional regulators or developmental control genes. Multiple lines of evidence suggest that HEY proteins primarily act as direct transcriptional repressors, while gene activation seems to be due to secondary or indirect effects. Mutagenesis of putative DNA binding residues supports the notion of direct DNA binding. While class B E-box sequences (CACGYG) clearly represent preferred target sequences, there must be additional and more loosely defined modes of DNA binding since many of the target promoters that are efficiently bound by HEY proteins do not contain an E-box motif. These data clearly establish the three HEY bHLH factors as highly redundant transcriptional repressors in vitro and in vivo, which explains the combinatorial action observed in different tissues with overlapping expression. PMID:22615585

Conservation demands safe gene drive

PubMed Central

Esvelt, Kevin M.

2017-01-01

Interest in developing gene drive systems to control invasive species is growing, with New Zealand reportedly considering the nascent technology as a way to locally eliminate the mammalian pests that threaten its unique flora and fauna. If gene drives successfully eradicated these invasive populations, many would rejoice, but what are the possible consequences? Here, we explore the risk of accidental spread posed by self-propagating gene drive technologies, highlight new gene drive designs that might achieve better outcomes, and explain why we need open and international discussions concerning a technology that could have global ramifications. PMID:29145398

Transcriptome analysis of tobacco BY-2 cells elicited by cryptogein reveals new potential actors of calcium-dependent and calcium-independent plant defense pathways.

PubMed

Amelot, Nicolas; Dorlhac de Borne, François; San Clemente, Hélène; Mazars, Christian; Grima-Pettenati, Jacqueline; Brière, Christian

2012-02-01

Cryptogein is a proteinaceous elicitor secreted by the oomycete Phytophthora cryptogea, which induces a hypersensitive response in tobacco plants. We have previously reported that in tobacco BY-2 cells treated with cryptogein, most of the genes of the phenylpropanoid pathway were upregulated and cell wall-bound phenolics accumulated. Both events were Ca(2+) dependent. In this study, we designed a microarray covering a large proportion of the tobacco genome and monitored gene expression in cryptogein-elicited BY-2 cells to get a more complete view of the transcriptome changes and to assess their Ca(2+) dependence. The predominant functional gene categories affected by cryptogein included stress- and disease-related proteins, phenylpropanoid pathway, signaling components, transcription factors and cell wall reinforcement. Among the 3819 unigenes whose expression changed more than fourfold, 90% were Ca(2+) dependent, as determined by their sensitivity to lanthanum chloride. The most Ca(2+)-dependent transcripts upregulated by cryptogein were involved in defense responses or the oxylipin pathway. This genome-wide study strongly supports the importance of Ca(2+)-dependent transcriptional regulation of regulatory and defense-related genes contributing to cryptogein responses in tobacco. Copyright © 2011 Elsevier Ltd. All rights reserved.

Development of an FHbp-CTB holotoxin-like chimera and the elicitation of bactericidal antibodies against serogroup B Neisseria meningitidis.

PubMed

Price, Gregory A; Bash, Margaret C

2018-01-29

The Neisseria meningitidis factor H binding protein (FHbp) is an important virulence factor and vaccine antigen contained in both USA licensed serogroup B meningococcal vaccines. Recent studies in human factor H (hFH) transgenic mice suggest that hFH-FHbp interactions lower FHbp-elicited immunogenicity. To provide tools with which to characterize and potentially improve FHbp immunogenicity, we developed an FHbp-cholera holotoxin-like chimera vaccine expression system in Escherichia coli that utilizes cholera toxin B (CTB) as both a scaffold and adjuvant for FHbp. We developed FHbp-CTB chimeras using a wild-type (WT) FHbp and a low hFH-binding FHbp mutant R41S. Both chimeras bound to G M1 ganglioside and were recognized by the FHbp-specific monoclonal antibody JAR4. The R41S mutant had greatly reduced hFH binding compared to the WT FHbp-CTB chimera. WT and R41S FHbp-CTB chimeric antigens were compared to equimolar amounts of FHbp admixed with CTB or FHbp alone in mouse immunogenicity studies. The chimeras were significantly more immunogenic than FHbp alone or mixed with CTB, and elicited bactericidal antibodies against a panel of MenB isolates. This study demonstrates a unique and simple method for studying FHbp immunogenicity. The chimeric approach may facilitate studies of other protein-based antigens targeting pathogenic Neisseria and lay groundwork for the development of new protein based vaccines against meningococcal and gonococcal disease. Published by Elsevier Ltd.

A film set for the elicitation of emotion in research: A comprehensive catalog derived from four decades of investigation.

PubMed

Gilman, T Lee; Shaheen, Razan; Nylocks, K Maria; Halachoff, Danielle; Chapman, Jessica; Flynn, Jessica J; Matt, Lindsey M; Coifman, Karin G

2017-12-01

Emotions are highly influential to many psychological processes. Indeed, research employing emotional stimuli is rapidly escalating across the field of psychology. However, challenges remain regarding discrete evocation of frequently co-elicited emotions such as amusement and happiness, or anger and disgust. Further, as much contemporary work in emotion employs college students, we sought to additionally evaluate the efficacy of film clips to discretely elicit these more challenging emotions in a young adult population using an online medium. The internet is an important tool for investigating responses to emotional stimuli, but validations of emotionally evocative film clips across laboratory and web-based settings are limited in the literature. An additional obstacle is identifying stimuli amidst the numerous film clip validation studies. During our investigation, we recognized the lack of a categorical database to facilitate rapid identification of useful film clips for individual researchers' unique investigations. Consequently, here we also sought to produce the first compilation of such stimuli into an accessible and comprehensive catalog. We based our catalog upon prior work as well as our own, and identified 24 articles and 295 film clips from four decades of research. We present information on the validation of these clips in addition to our own research validating six clips using online administration settings. The results of our search in the literature and our own study are presented in tables designed to facilitate and improve a selection of highly valid film stimuli for future research.

Phospholipase C mediates (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-, but not lysergic acid diethylamide (LSD)-elicited head bobs in rabbit medial prefrontal cortex.

PubMed

Schindler, Emmanuelle A D; Harvey, John A; Aloyo, Vincent J

2013-01-23

The phenethylamine and indoleamine classes of hallucinogens demonstrate distinct pharmacological properties, although they share a serotonin(2A) (5-HT(2A)) receptor mechanism of action (MOA). The 5-HT(2A) receptor signals through phosphatidylinositol (PI) hydrolysis, which is initiated upon activation of phospholipase C (PLC). The role of PI hydrolysis in the effects of hallucinogens remains unclear. In order to better understand the role of PI hydrolysis in the MOA of hallucinogens, the PLC inhibitor, 1-[6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione (U73122), was used to study the effects of two hallucinogens, the phenethylamine, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and the indoleamine, lysergic acid diethylamide (LSD). PI hydrolysis was quantified through release of [3H]inositol-4-phosphate from living rabbit frontocortical tissue prisms. Head bobs were counted after hallucinogens were infused into the medial prefrontal cortex (mPFC) of rabbits. Both DOI and LSD stimulated PI hydrolysis in frontocortical tissue through activation of PLC. DOI-stimulated PI hydrolysis was blocked by 5-HT(2A/2C) receptor antagonist, ketanserin, whereas the LSD signal was blocked by 5-HT(2B/2C) receptor antagonist, SB206553. When infused into the mPFC, both DOI- and LSD-elicited head bobs. Pretreatment with U73122 blocked DOI-, but not LSD-elicited head bobs. The two hallucinogens investigated were distinct in their activation of the PI hydrolysis signaling pathway. The serotonergic receptors involved with DOI and LSD signals in frontocortical tissue were different. Furthermore, PLC activation in mPFC was necessary for DOI-elicited head bobs, whereas LSD-elicited head bobs were independent of this pathway. These novel findings urge closer investigation into the intracellular mechanism of action of these unique compounds. Published by Elsevier B.V.

Analysis of propagation of Bacopa monnieri (L.) from hairy roots, elicitation and Bacoside A contents of Ri transformed plants.

PubMed

Largia, Muthiah Joe Virgin; Satish, Lakkakula; Johnsi, Rajaiah; Shilpha, Jayabalan; Ramesh, Manikandan

2016-08-01

Agrobacterium rhizogenes mediated transformation has been experimented in leaf explants of the memory herb Bacopa monnieri in order to assess the regeneration potential of hairy roots (HR) followed by the elicitation of transformed plants for increased Bacoside A production. Out of the four strains tested, A4 and MTCC 532 derived HR exhibited regrowth in MS basal medium while MTCC 2364 derived HR showed regeneration in MS medium supplemented with suitable phyto hormones. R1000 derived HR possessed no regeneration potential. Comparable to A4, MTCC 532 derived HR displayed maximum regrowth frequency of about 85.71 ± 1.84 % with an increase in biomass to threefold. Therefore, five HR plant lines (MTCC 532 derived) were generated and maintained in MS basal liquid medium in which HR3 topped the others in producing a huge biomass of about 67.09 ± 0.66 g FW. PCR amplification and southern hybridization analysis of rol A gene (280 bp) has been performed in order to confirm the transformation process. Moreover, HR3 plant line has accumulated highest total phenolic content of about 165.68 ± 0.82 mg GAE/g DW and highest total flavonoid content of about 497.78 ± 0.57 mg QRE/g DW when compared to other lines and untransformed controls. In addition, HR3 plant extract showed 85.58 ± 0.14 % of DPPH (2, 2-diphenyl-1-picryl hydrazyl) inhibition displaying its reliable anti oxidant potential. Further on elicitation with 10 mg/L chitosan for 2 weeks, HR3 has produced 5.83 % of Bacoside A which is fivefold and threefold increased production when compared to untransformed and transformed unelicited controls respectively. This is the first report on eliciting HR plants for increased metabolite accumulation in B. monnieri.

Unique pathway of expression of an opal suppressor phosphoserine tRNA.

PubMed Central

Lee, B J; de la Peña, P; Tobian, J A; Zasloff, M; Hatfield, D

1987-01-01

An opal suppressor phosphoserine tRNA gene is present in single copy in the genomes of higher vertebrates. We have shown that the product of this gene functions as a suppressor in an in vitro assay, and we have proposed that it may donate a modified amino acid directly to protein in response to specific UGA codons. In this report, we show through in vitro and in vivo studies that the human and Xenopus opal suppressor phosphoserine tRNAs are synthesized by a pathway that is, to the best of our knowledge, unlike that of any known eukaryotic tRNA. The primary transcript of this gene does not contain a 5'-leader sequence; and, therefore, transcription of this suppressor is initiated at the first nucleotide within the coding sequence. The 5'-terminal triphosphate, present on the primary transcript, remains intact through 3'-terminal maturation and through subsequent transport of the tRNA to the cytoplasm. The unique biosynthetic pathway of this opal suppressor may underlie its distinctive role in eukaryotic cells. Images PMID:3114749

CXC chemokine ligand 4 induces a unique transcriptome in monocyte-derived macrophages.

PubMed

Gleissner, Christian A; Shaked, Iftach; Little, Kristina M; Ley, Klaus

2010-05-01

In atherosclerotic arteries, blood monocytes differentiate to macrophages in the presence of growth factors, such as macrophage colony-stimulation factor (M-CSF), and chemokines, such as platelet factor 4 (CXCL4). To compare the gene expression signature of CXCL4-induced macrophages with M-CSF-induced macrophages or macrophages polarized with IFN-gamma/LPS (M1) or IL-4 (M2), we cultured primary human peripheral blood monocytes for 6 d. mRNA expression was measured by Affymetrix gene chips, and differences were analyzed by local pooled error test, profile of complex functionality, and gene set enrichment analysis. Three hundred seventy-five genes were differentially expressed between M-CSF- and CXCL4-induced macrophages; 206 of them overexpressed in CXCL4 macrophages coding for genes implicated in the inflammatory/immune response, Ag processing and presentation, and lipid metabolism. CXCL4-induced macrophages overexpressed some M1 and M2 genes and the corresponding cytokines at the protein level; however, their transcriptome clustered with neither M1 nor M2 transcriptomes. They almost completely lost the ability to phagocytose zymosan beads. Genes linked to atherosclerosis were not consistently upregulated or downregulated. Scavenger receptors showed lower and cholesterol efflux transporters showed higher expression in CXCL4- than M-CSF-induced macrophages, resulting in lower low-density lipoprotein content. We conclude that CXCL4 induces a unique macrophage transcriptome distinct from known macrophage types, defining a new macrophage differentiation that we propose to call M4.

Avirulence gene mapping in the Hessian fly (Mayetiola destructor) reveals a protein phosphatase 2C effector gene family.

PubMed

Zhao, Chaoyang; Shukle, Richard; Navarro-Escalante, Lucio; Chen, Mingshun; Richards, Stephen; Stuart, Jeffrey J

2016-01-01

The genetic tractability of the Hessian fly (HF, Mayetiola destructor) provides an opportunity to investigate the mechanisms insects use to induce plant gall formation. Here we demonstrate that capacity using the newly sequenced HF genome by identifying the gene (vH24) that elicits effector-triggered immunity in wheat (Triticum spp.) seedlings carrying HF resistance gene H24. vH24 was mapped within a 230-kb genomic fragment near the telomere of HF chromosome X1. That fragment contains only 21 putative genes. The best candidate vH24 gene in this region encodes a protein containing a secretion signal and a type-2 serine/threonine protein phosphatase (PP2C) domain. This gene has an H24-virulence associated insertion in its promoter that appears to silence transcription of the gene in H24-virulent larvae. Candidate vH24 is a member of a small family of genes that encode secretion signals and PP2C domains. It belongs to the fraction of genes in the HF genome previously predicted to encode effector proteins. Because PP2C proteins are not normally secreted, our results suggest that these are PP2C effectors that HF larvae inject into wheat cells to redirect, or interfere, with wheat signal transduction pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genomic identification of potential targets unique to Candida albicans for the discovery of antifungal agents.

PubMed

Tripathi, Himanshu; Luqman, Suaib; Meena, Abha; Khan, Feroz

2014-01-01

Despite of modern antifungal therapy, the mortality rates of invasive infection with human fungal pathogen Candida albicans are up to 40%. Studies suggest that drug resistance in the three most common species of human fungal pathogens viz., C. albicans, Aspergillus fumigatus (causing mortality rate up to 90%) and Cryptococcus neoformans (causing mortality rate up to 70%) is due to mutations in the target enzymes or high expression of drug transporter genes. Drug resistance in human fungal pathogens has led to an imperative need for the identification of new targets unique to fungal pathogens. In the present study, we have used a comparative genomics approach to find out potential target proteins unique to C. albicans, an opportunistic fungus responsible for severe infection in immune-compromised human. Interestingly, many target proteins of existing antifungal agents showed orthologs in human cells. To identify unique proteins, we have compared proteome of C. albicans [SC5314] i.e., 14,633 total proteins retrieved from the RefSeq database of NCBI, USA with proteome of human and non-pathogenic yeast Saccharomyces cerevisiae. Results showed that 4,568 proteins were identified unique to C. albicans as compared to those of human and later when these unique proteins were compared with S. cerevisiae proteome, finally 2,161 proteins were identified as unique proteins and after removing repeats total 1,618 unique proteins (42 functionally known, 1,566 hypothetical and 10 unknown) were selected as potential antifungal drug targets unique to C. albicans.

A modeling comparison of projection neuron- and neuromodulator-elicited oscillations in a central pattern generating network.

PubMed

Kintos, Nickolas; Nusbaum, Michael P; Nadim, Farzan

2008-06-01

Many central pattern generating networks are influenced by synaptic input from modulatory projection neurons. The network response to a projection neuron is sometimes mimicked by bath applying the neuronally-released modulator, despite the absence of network interactions with the projection neuron. One interesting example occurs in the crab stomatogastric ganglion (STG), where bath applying the neuropeptide pyrokinin (PK) elicits a gastric mill rhythm which is similar to that elicited by the projection neuron modulatory commissural neuron 1 (MCN1), despite the absence of PK in MCN1 and the fact that MCN1 is not active during the PK-elicited rhythm. MCN1 terminals have fast and slow synaptic actions on the gastric mill network and are presynaptically inhibited by this network in the STG. These local connections are inactive in the PK-elicited rhythm, and the mechanism underlying this rhythm is unknown. We use mathematical and biophysically-realistic modeling to propose potential mechanisms by which PK can elicit a gastric mill rhythm that is similar to the MCN1-elicited rhythm. We analyze slow-wave network oscillations using simplified mathematical models and, in parallel, develop biophysically-realistic models that account for fast, action potential-driven oscillations and some spatial structure of the network neurons. Our results illustrate how the actions of bath-applied neuromodulators can mimic those of descending projection neurons through mathematically similar but physiologically distinct mechanisms.

Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies

PubMed Central

deCamp, Allan; Hraber, Peter; Bailer, Robert T.; Seaman, Michael S.; Ochsenbauer, Christina; Kappes, John; Gottardo, Raphael; Edlefsen, Paul; Self, Steve; Tang, Haili; Greene, Kelli; Gao, Hongmei; Daniell, Xiaoju; Sarzotti-Kelsoe, Marcella; Gorny, Miroslaw K.; Zolla-Pazner, Susan; LaBranche, Celia C.; Mascola, John R.; Korber, Bette T.

2014-01-01

ABSTRACT Standardized assessments of HIV-1 vaccine-elicited neutralizing antibody responses are complicated by the genetic and antigenic variability of the viral envelope glycoproteins (Envs). To address these issues, suitable reference strains are needed that are representative of the global epidemic. Several panels have been recommended previously, but no clear answers have been available on how many and which strains are best suited for this purpose. We used a statistical model selection method to identify a global panel of reference Env clones from among 219 Env-pseudotyped viruses assayed in TZM-bl cells with sera from 205 HIV-1-infected individuals. The Envs and sera were sampled globally from diverse geographic locations and represented all major genetic subtypes and circulating recombinant forms of the virus. Assays with a panel size of only nine viruses adequately represented the spectrum of HIV-1 serum neutralizing activity seen with the larger panel of 219 viruses. An optimal panel of nine viruses was selected and augmented with three additional viruses for greater genetic and antigenic coverage. The spectrum of HIV-1 serum neutralizing activity seen with the final 12-virus panel closely approximated the activity seen with subtype-matched viruses. Moreover, the final panel was highly sensitive for detection of many of the known broadly neutralizing antibodies. For broader assay applications, all 12 Env clones were converted to infectious molecular clones using a proviral backbone carrying a Renilla luciferase reporter gene (Env.IMC.LucR viruses). This global panel should facilitate highly standardized assessments of vaccine-elicited neutralizing antibodies across multiple HIV-1 vaccine platforms in different parts of the world. IMPORTANCE An effective HIV-1 vaccine will need to overcome the extraordinary genetic variability of the virus, where most variation occurs in the viral envelope glycoproteins that are the sole targets for neutralizing antibodies

Global panel of HIV-1 Env reference strains for standardized assessments of vaccine-elicited neutralizing antibodies.

PubMed

deCamp, Allan; Hraber, Peter; Bailer, Robert T; Seaman, Michael S; Ochsenbauer, Christina; Kappes, John; Gottardo, Raphael; Edlefsen, Paul; Self, Steve; Tang, Haili; Greene, Kelli; Gao, Hongmei; Daniell, Xiaoju; Sarzotti-Kelsoe, Marcella; Gorny, Miroslaw K; Zolla-Pazner, Susan; LaBranche, Celia C; Mascola, John R; Korber, Bette T; Montefiori, David C

2014-03-01

Standardized assessments of HIV-1 vaccine-elicited neutralizing antibody responses are complicated by the genetic and antigenic variability of the viral envelope glycoproteins (Envs). To address these issues, suitable reference strains are needed that are representative of the global epidemic. Several panels have been recommended previously, but no clear answers have been available on how many and which strains are best suited for this purpose. We used a statistical model selection method to identify a global panel of reference Env clones from among 219 Env-pseudotyped viruses assayed in TZM-bl cells with sera from 205 HIV-1-infected individuals. The Envs and sera were sampled globally from diverse geographic locations and represented all major genetic subtypes and circulating recombinant forms of the virus. Assays with a panel size of only nine viruses adequately represented the spectrum of HIV-1 serum neutralizing activity seen with the larger panel of 219 viruses. An optimal panel of nine viruses was selected and augmented with three additional viruses for greater genetic and antigenic coverage. The spectrum of HIV-1 serum neutralizing activity seen with the final 12-virus panel closely approximated the activity seen with subtype-matched viruses. Moreover, the final panel was highly sensitive for detection of many of the known broadly neutralizing antibodies. For broader assay applications, all 12 Env clones were converted to infectious molecular clones using a proviral backbone carrying a Renilla luciferase reporter gene (Env.IMC.LucR viruses). This global panel should facilitate highly standardized assessments of vaccine-elicited neutralizing antibodies across multiple HIV-1 vaccine platforms in different parts of the world. An effective HIV-1 vaccine will need to overcome the extraordinary genetic variability of the virus, where most variation occurs in the viral envelope glycoproteins that are the sole targets for neutralizing antibodies. Efforts to elicit

Post-molting development of wind-elicited escape behavior in the cricket.

PubMed

Sato, Nodoka; Shidara, Hisashi; Ogawa, Hiroto

2017-11-01

Arthropods including insects grow through several developmental stages by molting. The abrupt changes in their body size and morphology accompanying the molting are responsible for the developmental changes in behavior. While in holometabolous insects, larval behaviors are transformed into adult-specific behaviors with drastic changes in nervous system during the pupal stage, hemimetabolous insects preserve most innate behaviors whole life long, which allow us to trace the maturation process of preserved behaviors after the changes in body. Wind-elicited escape behavior is one of these behaviors and mediated by cercal system, which is a mechanosensory organ equipped by all stages of nymph in orthopteran insects like crickets. However, the maturation process of the escape behavior after the molt is unclear. In this study, we examined time-series of changes in the wind-elicited escape behavior just after the imaginal molt in the cricket. The locomotor activities are developed over the elapsed time, and matured 24h after the molt. In contrast, a stimulus-angle dependency of moving direction was unchanged over time, meaning that the cercal sensory system detecting airflow direction was workable immediately after the molt, independent from the behavioral maturation. The post-molting development of the wind-elicited behavior was considered to result not simply from maturation of the exoskeleton or musculature because the escape response to heat-shock stimulus did not change after the molt. No effect of a temporal immobilization after the imaginal molt on the maturation of the wind-elicited behavior also implies that the maturation may be innately programmed without experience of locomotion. Copyright © 2017 Elsevier Ltd. All rights reserved.

Research Synthesis Methods in an Age of Globalized Risks: Lessons from the Global Burden of Foodborne Disease Expert Elicitation.

PubMed

2016-02-01

We live in an age that increasingly calls for national or regional management of global risks. This article discusses the contributions that expert elicitation can bring to efforts to manage global risks and identifies challenges faced in conducting expert elicitation at this scale. In doing so it draws on lessons learned from conducting an expert elicitation as part of the World Health Organizations (WHO) initiative to estimate the global burden of foodborne disease; a study commissioned by the Foodborne Disease Epidemiology Reference Group (FERG). Expert elicitation is designed to fill gaps in data and research using structured, transparent methods. Such gaps are a significant challenge for global risk modeling. Experience with the WHO FERG expert elicitation shows that it is feasible to conduct an expert elicitation at a global scale, but that challenges do arise, including: defining an informative, yet feasible geographical structure for the elicitation; defining what constitutes expertise in a global setting; structuring international, multidisciplinary expert panels; and managing demands on experts' time in the elicitation. This article was written as part of a workshop, "Methods for Research Synthesis: A Cross-Disciplinary Approach" held at the Harvard Center for Risk Analysis on October 13, 2013. © 2016 Society for Risk Analysis.

Functional Imaging of Human Vestibular Cortex Activity Elicited by Skull Tap and Auditory Tone Burst

NASA Technical Reports Server (NTRS)

Noohi, Fatemeh; Kinnaird, Catherine; Wood, Scott; Bloomberg, Jacob; Mulavara, Ajitkumar; Seidler, Rachael

2014-01-01

The aim of the current study was to characterize the brain activation in response to two modes of vestibular stimulation: skull tap and auditory tone burst. The auditory tone burst has been used in previous studies to elicit saccular Vestibular Evoked Myogenic Potentials (VEMP) (Colebatch & Halmagyi 1992; Colebatch et al. 1994). Some researchers have reported that airconducted skull tap elicits both saccular and utricle VEMPs, while being faster and less irritating for the subjects (Curthoys et al. 2009, Wackym et al., 2012). However, it is not clear whether the skull tap and auditory tone burst elicit the same pattern of cortical activity. Both forms of stimulation target the otolith response, which provides a measurement of vestibular function independent from semicircular canals. This is of high importance for studying the vestibular disorders related to otolith deficits. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, pre and post central gyri, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation (Bottini et al., 1994; Dieterich et al., 2003; Emri et al., 2003; Schlindwein et al., 2008; Janzen et al., 2008). Here we hypothesized that the skull tap elicits the similar pattern of cortical activity as the auditory tone burst. Subjects put on a set of MR compatible skull tappers and headphones inside the 3T GE scanner, while lying in supine position, with eyes closed. All subjects received both forms of the stimulation, however, the order of stimulation with auditory tone burst and air-conducted skull tap was counterbalanced across subjects. Pneumatically powered skull tappers were placed bilaterally on the cheekbones. The vibration of the cheekbone was transmitted to the vestibular cortex, resulting in vestibular response (Halmagyi et al., 1995). Auditory tone bursts were also delivered for comparison. To validate

Cue-elicited craving for food: a fresh approach to the study of binge eating.

PubMed

Sobik, Laura; Hutchison, Kent; Craighead, Linda

2005-06-01

Recent research has indicated that craving for food can be elicited by exposure to food cues, suggesting that exposure to food cues may represent a useful experimental paradigm to investigate mechanisms related to binge eating. The first objective of the present research was to replicate previous reports that exposure to food cues elicits craving for food. In addition, this investigation was designed to extend the extant literature by testing the effects of 'priming' portions of food, by examining the association between reactivity to food cues and indicators of binge eating, and to examine the role of a putative genetic factor previously found to be associated with cue-elicited craving for alcohol and tobacco. In Study 1, 48 individuals completed measures of craving and mood after exposure to control cues, after exposure to food cues, and after consuming each of three small portions of food. In Study 2, 31 individuals with subclinical symptoms of binge eating completed the same procedures. The results suggested that food cues reliably elicited craving, increased attention to the cues, and decreased positive affect in both samples, although reactivity was greater among the sample with greater eating pathology. Correlational analyses suggested that reactivity to food cues was correlated with binge eating and body mass index among women but not men. Results also suggest that the DRD4 VNTR polymorphism influences cue-elicited craving for food, although the influence of the DRD4 may depend on the population under study.

Cue-elicited anxiety and craving for food using virtual reality scenarios.

PubMed

Ferrer-García, Marta; Gutiérrez-Maldonado, José; Pla, Joana

2013-01-01

Cue exposure therapy has been reported to be an effective intervention for reducing binge eating behavior in patients with eating disorders and obesity. However, in vivo food exposure conducted in the therapist's office presents logistical problems and lacks ecological validity. This study proposes the use of virtual reality technology as an alternative to in vivo exposure, and assesses the ability of different virtual environments to elicit anxiety and craving for food in a non-clinical sample. The results show that exposure to virtual environments provokes changes in reported craving for food. High-calorie food cues are the ones that elicit the highest increases in craving.

Clustered Xenopus keratin genes: A genomic, transcriptomic, and proteomic analysis.

PubMed

Suzuki, Ken-Ichi T; Suzuki, Miyuki; Shigeta, Mitsuki; Fortriede, Joshua D; Takahashi, Shuji; Mawaribuchi, Shuuji; Yamamoto, Takashi; Taira, Masanori; Fukui, Akimasa

2017-06-15

Keratin genes belong to the intermediate filament superfamily and their expression is altered following morphological and physiological changes in vertebrate epithelial cells. Keratin genes are divided into two groups, type I and II, and are clustered on vertebrate genomes, including those of Xenopus species. Various keratin genes have been identified and characterized by their unique expression patterns throughout ontogeny in Xenopus laevis; however, compilation of previously reported and newly identified keratin genes in two Xenopus species is required for our further understanding of keratin gene evolution, not only in amphibians but also in all terrestrial vertebrates. In this study, 120 putative type I and II keratin genes in total were identified based on the genome data from two Xenopus species. We revealed that most of these genes are highly clustered on two homeologous chromosomes, XLA9_10 and XLA2 in X. laevis, and XTR10 and XTR2 in X. tropicalis, which are orthologous to those of human, showing conserved synteny among tetrapods. RNA-Seq data from various embryonic stages and adult tissues highlighted the unique expression profiles of orthologous and homeologous keratin genes in developmental stage- and tissue-specific manners. Moreover, we identified dozens of epidermal keratin proteins from the whole embryo, larval skin, tail, and adult skin using shotgun proteomics. In light of our results, we discuss the radiation, diversification, and unique expression of the clustered keratin genes, which are closely related to epidermal development and terrestrial adaptation during amphibian evolution, including Xenopus speciation. Copyright © 2016 Elsevier Inc. All rights reserved.

Naturalistic Observations of Elicited Expressive Communication of Children with Autism: An Analysis of Teacher Instructions

ERIC Educational Resources Information Center

Chiang, Hsu-Min

2009-01-01

This study observed expressive communication of 17 Australian and 15 Taiwanese children with autism who were mute or had limited spoken language during 2 hour regular school routines and analyzed teacher instructions associated with elicited expressive communication. Results indicated: (a) the frequency of occurrence of elicited expressive…

Functional hypervariability and gene diversity of cardioactive neuropeptides.

PubMed

Möller, Carolina; Melaun, Christian; Castillo, Cecilia; Díaz, Mary E; Renzelman, Chad M; Estrada, Omar; Kuch, Ulrich; Lokey, Scott; Marí, Frank

2010-12-24

Crustacean cardioactive peptide (CCAP) and related peptides are multifunctional regulatory neurohormones found in invertebrates. We isolated a CCAP-related peptide (conoCAP-a, for cone snail CardioActive Peptide) and cloned the cDNA of its precursor from venom of Conus villepinii. The precursor of conoCAP-a encodes for two additional CCAP-like peptides: conoCAP-b and conoCAP-c. This multi-peptide precursor organization is analogous to recently predicted molluscan CCAP-like preprohormones, and suggests a mechanism for the generation of biological diversification without gene amplification. While arthropod CCAP is a cardio-accelerator, we found that conoCAP-a decreases the heart frequency in Drosophila larvae, demonstrating that conoCAP-a and CCAP have opposite effects. Intravenous injection of conoCAP-a in rats caused decreased heart frequency and blood pressure in contrast to the injection of CCAP, which did not elicit any cardiac effect. Perfusion of rat ventricular cardiac myocytes with conoCAP-a decreased systolic calcium, indicating that conoCAP-a cardiac negative inotropic effects might be mediated via impairment of intracellular calcium trafficking. The contrasting cardiac effects of conoCAP-a and CCAP indicate that molluscan CCAP-like peptides have functions that differ from those of their arthropod counterparts. Molluscan CCAP-like peptides sequences, while homologous, differ between taxa and have unique sequences within a species. This relates to the functional hypervariability of these peptides as structure activity relationship studies demonstrate that single amino acids variations strongly affect cardiac activity. The discovery of conoCAPs in cone snail venom emphasizes the significance of their gene plasticity to have mutations as an adaptive evolution in terms of structure, cellular site of expression, and physiological functions.

Functional Hypervariability and Gene Diversity of Cardioactive Neuropeptides*

PubMed Central

Möller, Carolina; Melaun, Christian; Castillo, Cecilia; Díaz, Mary E.; Renzelman, Chad M.; Estrada, Omar; Kuch, Ulrich; Lokey, Scott; Marí, Frank

2010-01-01

Crustacean cardioactive peptide (CCAP) and related peptides are multifunctional regulatory neurohormones found in invertebrates. We isolated a CCAP-related peptide (conoCAP-a, for cone snail CardioActive Peptide) and cloned the cDNA of its precursor from venom of Conus villepinii. The precursor of conoCAP-a encodes for two additional CCAP-like peptides: conoCAP-b and conoCAP-c. This multi-peptide precursor organization is analogous to recently predicted molluscan CCAP-like preprohormones, and suggests a mechanism for the generation of biological diversification without gene amplification. While arthropod CCAP is a cardio-accelerator, we found that conoCAP-a decreases the heart frequency in Drosophila larvae, demonstrating that conoCAP-a and CCAP have opposite effects. Intravenous injection of conoCAP-a in rats caused decreased heart frequency and blood pressure in contrast to the injection of CCAP, which did not elicit any cardiac effect. Perfusion of rat ventricular cardiac myocytes with conoCAP-a decreased systolic calcium, indicating that conoCAP-a cardiac negative inotropic effects might be mediated via impairment of intracellular calcium trafficking. The contrasting cardiac effects of conoCAP-a and CCAP indicate that molluscan CCAP-like peptides have functions that differ from those of their arthropod counterparts. Molluscan CCAP-like peptides sequences, while homologous, differ between taxa and have unique sequences within a species. This relates to the functional hypervariability of these peptides as structure activity relationship studies demonstrate that single amino acids variations strongly affect cardiac activity. The discovery of conoCAPs in cone snail venom emphasizes the significance of their gene plasticity to have mutations as an adaptive evolution in terms of structure, cellular site of expression, and physiological functions. PMID:20923766

Unique geologic insights from "non-unique" gravity and magnetic interpretation

USGS Publications Warehouse

Saltus, R.W.; Blakely, R.J.

2011-01-01

Interpretation of gravity and magnetic anomalies is mathematically non-unique because multiple theoretical solutions are always possible. The rigorous mathematical label of "nonuniqueness" can lead to the erroneous impression that no single interpretation is better in a geologic sense than any other. The purpose of this article is to present a practical perspective on the theoretical non-uniqueness of potential-field interpretation in geology. There are multiple ways to approach and constrain potential-field studies to produce significant, robust, and definitive results. The "non-uniqueness" of potential-field studies is closely related to the more general topic of scientific uncertainty in the Earth sciences and beyond. Nearly all results in the Earth sciences are subject to significant uncertainty because problems are generally addressed with incomplete and imprecise data. The increasing need to combine results from multiple disciplines into integrated solutions in order to address complex global issues requires special attention to the appreciation and communication of uncertainty in geologic interpretation.

Effect of elicitation on growth, respiration, and nutrient uptake of root and cell suspension cultures of Hyoscyamus muticus.

PubMed

Carvalho, Edgard B; Curtis, Wayne R

2002-01-01

The elicitation of Hyoscyamus muticus root and cell suspension cultures by fungal elicitor from Rhizoctonia solani causes dramatic changes in respiration, nutrient yields, and growth. Cells and mature root tissues have similar specific oxygen uptake rates (SOUR) before and after the onset of the elicitation process. Cell suspension SOUR were 11 and 18 micromol O2/g FW x h for non-elicited control and elicited cultures, respectively. Mature root SOUR were 11 and 24 micromol O2/g FW x h for control and elicited tissue, respectively. Tissue growth is significantly reduced upon the addition of elicitor to these cultures. Inorganic yield remains fairly constant, whereas yield on sugar is reduced from 0.532 to 0.352 g dry biomass per g sugar for roots and 0.614 to 0.440 g dry biomass per g sugar for cells. This reduction in yield results from increased energy requirements for the defense response. Growth reduction is reflected in a reduction in root meristem (tip) SOUR, which decreased from 189 to 70 micromol O2/g FW x h upon elicitation. Therefore, despite the increase in total respiration, the maximum local oxygen fluxes are reduced as a result of the reduction in metabolic activity at the meristem. This distribution of oxygen uptake throughout the mature tissue could reduce mass transfer requirements during elicited production. However, this was not found to be the case for sesquiterpene elicitation, where production of lubimin and solavetivone were found to increase linearly up to oxygen partial pressures of 40% O2 in air. SOUR is shown to similarly increase in both bubble column and tubular reactors despite severe mass transfer limitations, suggesting the possibility of metabolically induced increases in tissue convective transport during elicitation.

The pkI gene encoding pyruvate kinase I links to the luxZ gene which enhances bioluminescence of the lux operon from Photobacterium leiognathi.

PubMed

Lin, J W; Lu, H C; Chen, H Y; Weng, S F

1997-10-09

Partial 3'-end nucleotide sequence of the pkI gene (GenBank accession No. AF019143) from Photobacterium leiognathi ATCC 25521 has been determined, and the encoded pyruvate kinase I is deduced. Pyruvate kinase I is the key enzyme of glycolysis, which converts phosphoenol pyruvate to pyruvate. Alignment and comparison of pyruvate kinase Is from P. leiognathi, E. coli and Salmonella typhimurium show that they are homologous. Nucleotide sequence reveals that the pkI gene is linked to the luxZ gene that enhances bioluminescence of the lux operon from P. leiognathi. The gene order of the pkI and luxZ genes is-pk1-ter-->-R&R"-luxZ-ter"-->, whereas ter is transcriptional terminator for the pkI and related genes, and R&R" is the regulatory region and ter" is transcriptional terminator for the luxZ gene. It clearly elicits that the pkI gene and luxZ gene are divided to two operons. Functional analysis confirms that the potential hairpin loop omega T is the transcriptional terminator for the pkI and related genes. It infers that the pkI and related genes are simply linked to the luxZ gene in P. leiognathi genome.

Co-Option and De Novo Gene Evolution Underlie Molluscan Shell Diversity

PubMed Central

Aguilera, Felipe; McDougall, Carmel

2017-01-01

Abstract Molluscs fabricate shells of incredible diversity and complexity by localized secretions from the dorsal epithelium of the mantle. Although distantly related molluscs express remarkably different secreted gene products, it remains unclear if the evolution of shell structure and pattern is underpinned by the differential co-option of conserved genes or the integration of lineage-specific genes into the mantle regulatory program. To address this, we compare the mantle transcriptomes of 11 bivalves and gastropods of varying relatedness. We find that each species, including four Pinctada (pearl oyster) species that diverged within the last 20 Ma, expresses a unique mantle secretome. Lineage- or species-specific genes comprise a large proportion of each species’ mantle secretome. A majority of these secreted proteins have unique domain architectures that include repetitive, low complexity domains (RLCDs), which evolve rapidly, and have a proclivity to expand, contract and rearrange in the genome. There are also a large number of secretome genes expressed in the mantle that arose before the origin of gastropods and bivalves. Each species expresses a unique set of these more ancient genes consistent with their independent co-option into these mantle gene regulatory networks. From this analysis, we infer lineage-specific secretomes underlie shell diversity, and include both rapidly evolving RLCD-containing proteins, and the continual recruitment and loss of both ancient and recently evolved genes into the periphery of the regulatory network controlling gene expression in the mantle epithelium. PMID:28053006

Distinct Patterns of Gene and Protein Expression Elicited by Organophosphorus Pesticides in Caenorhabditis elegans

DTIC Science & Technology

2009-01-01

them an important concern for public health. OPs are a class of chemicals that inhibit serine esterases by covalently bonding with the active site...K03E5.2 gene product, which contains a calponin repeat, is also induced. Calponins may play a role in regulation of myosin ATPase activity and muscle...indication of apoptotic activity is an apparent change in sphingolipid metabolism in OP exposed worms. The sphingolipid metabolites, ceramide and

Variation in umami perception and in candidate genes for the umami receptor in mice and humans1234

PubMed Central

Shirosaki, Shinya; Ohkuri, Tadahiro; Sanematsu, Keisuke; Islam, AA Shahidul; Ogiwara, Yoko; Kawai, Misako; Yoshida, Ryusuke; Ninomiya, Yuzo

2009-01-01

The unique taste induced by monosodium glutamate is referred to as umami taste. The umami taste is also elicited by the purine nucleotides inosine 5′-monophosphate and guanosine 5′-monophosphate. There is evidence that a heterodimeric G protein–coupled receptor, which consists of the T1R1 (taste receptor type 1, member 1, Tas1r1) and the T1R3 (taste receptor type 1, member 3, Tas1r3) proteins, functions as an umami taste receptor for rodents and humans. Splice variants of metabotropic glutamate receptors, mGluR1 (glutamate receptor, metabotropic 1, Grm1) and mGluR4 (glutamate receptor, metabotropic 4, Grm4), also have been proposed as taste receptors for glutamate. The taste sensitivity to umami substances varies in inbred mouse strains and in individual humans. However, little is known about the relation of umami taste sensitivity to variations in candidate umami receptor genes in rodents or in humans. In this article, we summarize current knowledge of the diversity of umami perception in mice and humans. Furthermore, we combine previously published data and new information from the single nucleotide polymorphism databases regarding variation in the mouse and human candidate umami receptor genes: mouse Tas1r1 (TAS1R1 for human), mouse Tas1r3 (TAS1R3 for human), mouse Grm1 (GRM1 for human), and mouse Grm4 (GRM4 for human). Finally, we discuss prospective associations between variation of these genes and umami taste perception in both species. PMID:19625681

Neutral and Non-Neutral Evolution of Duplicated Genes with Gene Conversion

PubMed Central

Fawcett, Jeffrey A.; Innan, Hideki

2011-01-01

Gene conversion is one of the major mutational mechanisms involved in the DNA sequence evolution of duplicated genes. It contributes to create unique patters of DNA polymorphism within species and divergence between species. A typical pattern is so-called concerted evolution, in which the divergence between duplicates is maintained low for a long time because of frequent exchanges of DNA fragments. In addition, gene conversion affects the DNA evolution of duplicates in various ways especially when selection operates. Here, we review theoretical models to understand the evolution of duplicates in both neutral and non-neutral cases. We also explain how these theories contribute to interpreting real polymorphism and divergence data by using some intriguing examples. PMID:24710144

Model-Eliciting Activities (MEAs) as a Bridge between Engineering Education Research and Mathematics Education Research

ERIC Educational Resources Information Center

Hamilton, Eric; Lesh, Richard; Lester, Frank; Brilleslyper, Michael

2008-01-01

This article introduces Model-Eliciting Activities (MEAs) as a form of case study team problem-solving. MEA design focuses on eliciting from students conceptual models that they iteratively revise in problem-solving. Though developed by mathematics education researchers to study the evolution of mathematical problem-solving expertise in middle…

Expert elicitation survey on future wind energy costs

DOE PAGES

Wiser, Ryan; Jenni, Karen; Seel, Joachim; ...

2016-09-12

Wind energy supply has grown rapidly over the last decade. However, the long-term contribution of wind to future energy supply, and the degree to which policy support is necessary to motivate higher levels of deployment, depends - in part - on the future costs of both onshore and offshore wind. In this paper, we summarize the results of an expert elicitation survey of 163 of the world's foremost wind experts, aimed at better understanding future costs and technology advancement possibilities. Results suggest significant opportunities for cost reductions, but also underlying uncertainties. Under the median scenario, experts anticipate 24-30% reductions bymore » 2030 and 35-41% reductions by 2050 across the three wind applications studied. Costs could be even lower: experts predict a 10% chance that reductions will be more than 40% by 2030 and more than 50% by 2050. Insights gained through expert elicitation complement other tools for evaluating cost-reduction potential, and help inform policy and planning, R & D and industry strategy.« less

Expert elicitation for a national-level volcano hazard model

NASA Astrophysics Data System (ADS)

Bebbington, Mark; Stirling, Mark; Cronin, Shane; Wang, Ting; Jolly, Gill

2016-04-01

The quantification of volcanic hazard at national level is a vital pre-requisite to placing volcanic risk on a platform that permits meaningful comparison with other hazards such as earthquakes. New Zealand has up to a dozen dangerous volcanoes, with the usual mixed degrees of knowledge concerning their temporal and spatial eruptive history. Information on the 'size' of the eruptions, be it in terms of VEI, volume or duration, is sketchy at best. These limitations and the need for a uniform approach lend themselves to a subjective hazard analysis via expert elicitation. Approximately 20 New Zealand volcanologists provided estimates for the size of the next eruption from each volcano and, conditional on this, its location, timing and duration. Opinions were likewise elicited from a control group of statisticians, seismologists and (geo)chemists, all of whom had at least heard the term 'volcano'. The opinions were combined via the Cooke classical method. We will report on the preliminary results from the exercise.

Expert elicitation survey on future wind energy costs

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

Wiser, Ryan; Jenni, Karen; Seel, Joachim

Wind energy supply has grown rapidly over the last decade. However, the long-term contribution of wind to future energy supply, and the degree to which policy support is necessary to motivate higher levels of deployment, depends -- in part -- on the future costs of both onshore and offshore wind. Here, we summarize the results of an expert elicitation survey of 163 of the world's foremost wind experts, aimed at better understanding future costs and technology advancement possibilities. Results suggest significant opportunities for cost reductions, but also underlying uncertainties. Under the median scenario, experts anticipate 24-30% reductions by 2030 andmore » 35-41% reductions by 2050 across the three wind applications studied. Costs could be even lower: experts predict a 10% chance that reductions will be more than 40% by 2030 and more than 50% by 2050. Insights gained through expert elicitation complement other tools for evaluating cost-reduction potential, and help inform policy and planning, R&D and industry strategy.« less

Expert elicitation survey on future wind energy costs

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

Wiser, Ryan; Jenni, Karen; Seel, Joachim

Wind energy supply has grown rapidly over the last decade. However, the long-term contribution of wind to future energy supply, and the degree to which policy support is necessary to motivate higher levels of deployment, depends - in part - on the future costs of both onshore and offshore wind. In this paper, we summarize the results of an expert elicitation survey of 163 of the world's foremost wind experts, aimed at better understanding future costs and technology advancement possibilities. Results suggest significant opportunities for cost reductions, but also underlying uncertainties. Under the median scenario, experts anticipate 24-30% reductions bymore » 2030 and 35-41% reductions by 2050 across the three wind applications studied. Costs could be even lower: experts predict a 10% chance that reductions will be more than 40% by 2030 and more than 50% by 2050. Insights gained through expert elicitation complement other tools for evaluating cost-reduction potential, and help inform policy and planning, R & D and industry strategy.« less

A cell wall-degrading esterase of Xanthomonas oryzae requires a unique substrate recognition module for pathogenesis on rice.

PubMed

Aparna, Gudlur; Chatterjee, Avradip; Sonti, Ramesh V; Sankaranarayanan, Rajan

2009-06-01

Xanthomonas oryzae pv oryzae (Xoo) causes bacterial blight, a serious disease of rice (Oryza sativa). LipA is a secretory virulence factor of Xoo, implicated in degradation of rice cell walls and the concomitant elicitation of innate immune responses, such as callose deposition and programmed cell death. Here, we present the high-resolution structural characterization of LipA that reveals an all-helical ligand binding module as a distinct functional attachment to the canonical hydrolase catalytic domain. We demonstrate that the enzyme binds to a glycoside ligand through a rigid pocket comprising distinct carbohydrate-specific and acyl chain recognition sites where the catalytic triad is situated 15 A from the anchored carbohydrate. Point mutations disrupting the carbohydrate anchor site or blocking the pocket, even at a considerable distance from the enzyme active site, can abrogate in planta LipA function, exemplified by loss of both virulence and the ability to elicit host defense responses. A high conservation of the module across genus Xanthomonas emphasizes the significance of this unique plant cell wall-degrading function for this important group of plant pathogenic bacteria. A comparison with the related structural families illustrates how a typical lipase is recruited to act on plant cell walls to promote virulence, thus providing a remarkable example of the emergence of novel functions around existing scaffolds for increased proficiency of pathogenesis during pathogen-plant coevolution.

Unique features of a global human ectoparasite identified through sequencing of the bed bug genome.

PubMed

Benoit, Joshua B; Adelman, Zach N; Reinhardt, Klaus; Dolan, Amanda; Poelchau, Monica; Jennings, Emily C; Szuter, Elise M; Hagan, Richard W; Gujar, Hemant; Shukla, Jayendra Nath; Zhu, Fang; Mohan, M; Nelson, David R; Rosendale, Andrew J; Derst, Christian; Resnik, Valentina; Wernig, Sebastian; Menegazzi, Pamela; Wegener, Christian; Peschel, Nicolai; Hendershot, Jacob M; Blenau, Wolfgang; Predel, Reinhard; Johnston, Paul R; Ioannidis, Panagiotis; Waterhouse, Robert M; Nauen, Ralf; Schorn, Corinna; Ott, Mark-Christoph; Maiwald, Frank; Johnston, J Spencer; Gondhalekar, Ameya D; Scharf, Michael E; Peterson, Brittany F; Raje, Kapil R; Hottel, Benjamin A; Armisén, David; Crumière, Antonin Jean Johan; Refki, Peter Nagui; Santos, Maria Emilia; Sghaier, Essia; Viala, Sèverine; Khila, Abderrahman; Ahn, Seung-Joon; Childers, Christopher; Lee, Chien-Yueh; Lin, Han; Hughes, Daniel S T; Duncan, Elizabeth J; Murali, Shwetha C; Qu, Jiaxin; Dugan, Shannon; Lee, Sandra L; Chao, Hsu; Dinh, Huyen; Han, Yi; Doddapaneni, Harshavardhan; Worley, Kim C; Muzny, Donna M; Wheeler, David; Panfilio, Kristen A; Vargas Jentzsch, Iris M; Vargo, Edward L; Booth, Warren; Friedrich, Markus; Weirauch, Matthew T; Anderson, Michelle A E; Jones, Jeffery W; Mittapalli, Omprakash; Zhao, Chaoyang; Zhou, Jing-Jiang; Evans, Jay D; Attardo, Geoffrey M; Robertson, Hugh M; Zdobnov, Evgeny M; Ribeiro, Jose M C; Gibbs, Richard A; Werren, John H; Palli, Subba R; Schal, Coby; Richards, Stephen

2016-02-02

The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host-symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human-bed bug and symbiont-bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.

Unique features of a global human ectoparasite identified through sequencing of the bed bug genome

PubMed Central

Benoit, Joshua B.; Adelman, Zach N.; Reinhardt, Klaus; Dolan, Amanda; Poelchau, Monica; Jennings, Emily C.; Szuter, Elise M.; Hagan, Richard W.; Gujar, Hemant; Shukla, Jayendra Nath; Zhu, Fang; Mohan, M.; Nelson, David R.; Rosendale, Andrew J.; Derst, Christian; Resnik, Valentina; Wernig, Sebastian; Menegazzi, Pamela; Wegener, Christian; Peschel, Nicolai; Hendershot, Jacob M.; Blenau, Wolfgang; Predel, Reinhard; Johnston, Paul R.; Ioannidis, Panagiotis; Waterhouse, Robert M.; Nauen, Ralf; Schorn, Corinna; Ott, Mark-Christoph; Maiwald, Frank; Johnston, J. Spencer; Gondhalekar, Ameya D.; Scharf, Michael E.; Peterson, Brittany F.; Raje, Kapil R.; Hottel, Benjamin A.; Armisén, David; Crumière, Antonin Jean Johan; Refki, Peter Nagui; Santos, Maria Emilia; Sghaier, Essia; Viala, Sèverine; Khila, Abderrahman; Ahn, Seung-Joon; Childers, Christopher; Lee, Chien-Yueh; Lin, Han; Hughes, Daniel S. T.; Duncan, Elizabeth J.; Murali, Shwetha C.; Qu, Jiaxin; Dugan, Shannon; Lee, Sandra L.; Chao, Hsu; Dinh, Huyen; Han, Yi; Doddapaneni, Harshavardhan; Worley, Kim C.; Muzny, Donna M.; Wheeler, David; Panfilio, Kristen A.; Vargas Jentzsch, Iris M.; Vargo, Edward L.; Booth, Warren; Friedrich, Markus; Weirauch, Matthew T.; Anderson, Michelle A. E.; Jones, Jeffery W.; Mittapalli, Omprakash; Zhao, Chaoyang; Zhou, Jing-Jiang; Evans, Jay D.; Attardo, Geoffrey M.; Robertson, Hugh M.; Zdobnov, Evgeny M.; Ribeiro, Jose M. C.; Gibbs, Richard A.; Werren, John H.; Palli, Subba R.; Schal, Coby; Richards, Stephen

2016-01-01

The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite. PMID:26836814

Dynamic Assessment of Elicited Imitation: A Case Analysis of an Advanced L2 English Speaker

ERIC Educational Resources Information Center

van Compernolle, Rémi A.; Zhang, Haomin

2014-01-01

The focus of this paper is on the design, administration, and scoring of a dynamically administered elicited imitation test of L2 English morphology. Drawing on Vygotskian sociocultural psychology, particularly the concepts of zone of proximal development and dynamic assessment, we argue that support provided during the elicited imitation test…

Exposure to the taste of alcohol elicits activation of the mesocorticolimbic neurocircuitry.

PubMed

Filbey, Francesca M; Claus, Eric; Audette, Amy R; Niculescu, Michelle; Banich, Marie T; Tanabe, Jody; Du, Yiping P; Hutchison, Kent E

2008-05-01

A growing number of imaging studies suggest that alcohol cues, mainly visual, elicit activation in mesocorticolimbic structures. Such findings are consistent with the growing recognition that these structures play an important role in the attribution of incentive salience and the pathophysiology of addiction. The present study investigated whether the presentation of alcohol taste cues can activate brain regions putatively involved in the acquisition and expression of incentive salience. Using functional magnetic resonance imaging, we recorded BOLD activity while delivering alcoholic tastes to 37 heavy drinking but otherwise healthy volunteers. The results yielded a pattern of BOLD activity in mesocorticolimbic structures (ie prefrontal cortex, striatum, ventral tegmental area/substantia nigra) relative to an appetitive control. Further analyses suggested strong connectivity between these structures during cue-elicited urge and demonstrated significant positive correlations with a measure of alcohol use problems (ie the Alcohol Use Disorders Identification Test). Thus, repeated exposure to the taste alcohol in the scanner elicits activation in mesocorticolimbic structures, and this activation is related to measures of urge and severity of alcohol problems.

Exposure to the Taste of Alcohol Elicits Activation of the Mesocorticolimbic Neurocircuitry

PubMed Central

Filbey, Francesca M; Claus, Eric; Audette, Amy R; Niculescu, Michelle; Banich, Marie T; Tanabe, Jody; Du, Yiping P; Hutchison, Kent E

2010-01-01

A growing number of imaging studies suggest that alcohol cues, mainly visual, elicit activation in mesocorticolimbic structures. Such findings are consistent with the growing recognition that these structures play an important role in the attribution of incentive salience and the pathophysiology of addiction. The present study investigated whether the presentation of alcohol taste cues can activate brain regions putatively involved in the acquisition and expression of incentive salience. Using functional magnetic resonance imaging, we recorded BOLD activity while delivering alcoholic tastes to 37 heavy drinking but otherwise healthy volunteers. The results yielded a pattern of BOLD activity in mesocorticolimbic structures (ie prefrontal cortex, striatum, ventral tegmental area/substantia nigra) relative to an appetitive control. Further analyses suggested strong connectivity between these structures during cue-elicited urge and demonstrated significant positive correlations with a measure of alcohol use problems (ie the Alcohol Use Disorders Identification Test). Thus, repeated exposure to the taste alcohol in the scanner elicits activation in mesocorticolimbic structures, and this activation is related to measures of urge and severity of alcohol problems. PMID:17653109

Cellular requirements for cutaneous sensitivity elicitation.

PubMed

Aoki, I

1985-01-01

The role of glass-adherent cells in cutaneous sensitivity (CS) elicitation has been analyzed in this study. CS responses have been revealed to be mediated by at least two distinct subsets of genetically restricted T cells: I-restricted 'DTH-like' T cells and K/D-restricted 'CTL-like' T cells. Both T-cell responses require I-A-positive glass-adherent cell populations, which lack T-cell markers, to manifest their activities. The role of the adherent cells is different in the 'DTH-like' responses and the 'CTL-like' responses. The disparities between the present results and previous contentions are discussed in this paper.

Investigating Oxidative Stress and Inflammatory Responses Elicited by Silver Nanoparticles Using High-Throughput Reporter Genes in HepG2 Cells: Effect of Size, Surface Coating, and Intracellular Uptake

EPA Science Inventory

Abstract Silver nanoparticles (Ag NP) have been shown to generate reactive oxygen species; however, the association between physicochemical characteristics of nanoparticles and cellular stress responses elicited by exposure has not been elucidated. Here, we examined three key...

Estimating unknown parameters in haemophilia using expert judgement elicitation.

PubMed

Fischer, K; Lewandowski, D; Janssen, M P

2013-09-01

The increasing attention to healthcare costs and treatment efficiency has led to an increasing demand for quantitative data concerning patient and treatment characteristics in haemophilia. However, most of these data are difficult to obtain. The aim of this study was to use expert judgement elicitation (EJE) to estimate currently unavailable key parameters for treatment models in severe haemophilia A. Using a formal expert elicitation procedure, 19 international experts provided information on (i) natural bleeding frequency according to age and onset of bleeding, (ii) treatment of bleeds, (iii) time needed to control bleeding after starting secondary prophylaxis, (iv) dose requirements for secondary prophylaxis according to onset of bleeding, and (v) life-expectancy. For each parameter experts provided their quantitative estimates (median, P10, P90), which were combined using a graphical method. In addition, information was obtained concerning key decision parameters of haemophilia treatment. There was most agreement between experts regarding bleeding frequencies for patients treated on demand with an average onset of joint bleeding (1.7 years): median 12 joint bleeds per year (95% confidence interval 0.9-36) for patients ≤ 18, and 11 (0.8-61) for adult patients. Less agreement was observed concerning estimated effective dose for secondary prophylaxis in adults: median 2000 IU every other day The majority (63%) of experts expected that a single minor joint bleed could cause irreversible damage, and would accept up to three minor joint bleeds or one trauma related joint bleed annually on prophylaxis. Expert judgement elicitation allowed structured capturing of quantitative expert estimates. It generated novel data to be used in computer modelling, clinical care, and trial design. © 2013 John Wiley & Sons Ltd.

Emotion Elicitation: A Comparison of Pictures and Films

PubMed Central

Uhrig, Meike K.; Trautmann, Nadine; Baumgärtner, Ulf; Treede, Rolf-Detlef; Henrich, Florian; Hiller, Wolfgang; Marschall, Susanne

2016-01-01

Pictures and film clips are widely used and accepted stimuli to elicit emotions. Based on theoretical arguments it is often assumed that the emotional effects of films exceed those of pictures, but to date this assumption has not been investigated directly. The aim of the present study was to compare pictures and films in terms of their capacity to induce emotions verified by means of explicit measures. Stimuli were (a) single pictures presented for 6 s, (b) a set of three consecutive pictures with emotionally congruent contents presented for 2 s each, (c) short film clips with a duration of 6 s. A total of 144 participants rated their emotion and arousal states following stimulus presentation. Repeated-measures ANOVAs revealed that the film clips and 3-picture version were as effective as the classical 1-picture method to elicit positive emotions, however, modulation toward positive valence was little. Modulation toward negative valence was more effective in general. Film clips were less effective than pictorial stimuli in producing the corresponding emotion states (all p < 0.001) and were less arousing (all p ≤ 0.02). Possible reasons for these unexpected results are discussed. PMID:26925007

Emotion Elicitation: A Comparison of Pictures and Films.

PubMed

Uhrig, Meike K; Trautmann, Nadine; Baumgärtner, Ulf; Treede, Rolf-Detlef; Henrich, Florian; Hiller, Wolfgang; Marschall, Susanne

2016-01-01

Pictures and film clips are widely used and accepted stimuli to elicit emotions. Based on theoretical arguments it is often assumed that the emotional effects of films exceed those of pictures, but to date this assumption has not been investigated directly. The aim of the present study was to compare pictures and films in terms of their capacity to induce emotions verified by means of explicit measures. Stimuli were (a) single pictures presented for 6 s, (b) a set of three consecutive pictures with emotionally congruent contents presented for 2 s each, (c) short film clips with a duration of 6 s. A total of 144 participants rated their emotion and arousal states following stimulus presentation. Repeated-measures ANOVAs revealed that the film clips and 3-picture version were as effective as the classical 1-picture method to elicit positive emotions, however, modulation toward positive valence was little. Modulation toward negative valence was more effective in general. Film clips were less effective than pictorial stimuli in producing the corresponding emotion states (all p < 0.001) and were less arousing (all p ≤ 0.02). Possible reasons for these unexpected results are discussed.

Interviewing strategically to elicit admissions from guilty suspects.

PubMed

Tekin, Serra; Granhag, Pär Anders; Strömwall, Leif; Giolla, Erik Mac; Vrij, Aldert; Hartwig, Maria

2015-06-01

In this article we introduce a novel interviewing tactic to elicit admissions from guilty suspects. By influencing the suspects' perception of the amount of evidence the interviewer holds against them, we aimed to shift the suspects' counterinterrogation strategies from less to more forthcoming. The proposed tactic (SUE-Confrontation) is a development of the Strategic Use of Evidence (SUE) framework and aims to affect the suspects' perception by confronting them with statement-evidence inconsistencies. Participants (N = 90) were asked to perform several mock criminal tasks before being interviewed using 1 of 3 interview techniques: (a) SUE-Confrontation, (b) Early Disclosure of Evidence, or (c) No Disclosure of Evidence. As predicted, the SUE-Confrontation interview generated more statement-evidence inconsistencies from suspects than the Early Disclosure interview. Importantly, suspects in the SUE-Confrontation condition (vs. Early and No disclosure conditions) admitted more self-incriminating information and also perceived the interviewer to have had more information about the critical phase of the crime (the phase where the interviewer lacked evidence). The findings show the adaptability of the SUE-technique and how it may be used as a tool for eliciting admissions. (c) 2015 APA, all rights reserved).

Snapchat elicits more jealousy than Facebook: a comparison of Snapchat and Facebook use.

PubMed

Utz, Sonja; Muscanell, Nicole; Khalid, Cameran

2015-03-01

Recent news in the media has suggested that younger people are using popular social media such as Facebook less and are quickly adopting newer media, such as the self-destructing app Snapchat. Snapchat is unique in that it erases messages several seconds after they have been sent, affording its users a higher level of privacy. Yet, little research exists on Snapchat use in general, let alone its broader psychological implications. This article offers a preliminary comparison of Snapchat and Facebook use and psychological effects on romantic jealousy. General motives for using Snapchat and Facebook are examined, as well as the nature of the content that Snapchat users most frequently share. Further, because of the differences in privacy and persistence of information, potential psychological effects in the domain of romantic jealousy are also examined, which has been widely studied on Facebook in the last few years. Findings show that the main difference in motives were that Snapchat was used more for flirting and finding new love interests, whereas Facebook was still the main social networking site used for keeping in touch with friends. Further, when presenting users with a series of potentially jealousy provoking scenarios, Snapchat elicited higher levels of jealousy than did Facebook. These findings are explained based on an affordance approach.

Applying horizontal gene transfer phenomena to enhance non-viral gene therapy

PubMed Central

Elmer, Jacob J.; Christensen, Matthew D.; Rege, Kaushal

2014-01-01

Horizontal gene transfer (HGT) is widespread amongst prokaryotes, but eukaryotes tend to be far less promiscuous with their genetic information. However, several examples of HGT from pathogens into eukaryotic cells have been discovered and mimicked to improve non-viral gene delivery techniques. For example, several viral proteins and DNA sequences have been used to significantly increase cytoplasmic and nuclear gene delivery. Plant genetic engineering is routinely performed with the pathogenic bacterium Agrobacterium tumefaciens and similar pathogens (e.g. Bartonella henselae) may also be able to transform human cells. Intracellular parasites like Trypanosoma cruzi may also provide new insights into overcoming cellular barriers to gene delivery. Finally, intercellular nucleic acid transfer between host cells will also be briefly discussed. This article will review the unique characteristics of several different viruses and microbes and discuss how their traits have been successfully applied to improve non-viral gene delivery techniques. Consequently, pathogenic traits that originally caused diseases may eventually be used to treat many genetic diseases. PMID:23994344

Visual gene developer: a fully programmable bioinformatics software for synthetic gene optimization.

PubMed

Jung, Sang-Kyu; McDonald, Karen

2011-08-16

Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interface, but also includes unique features such as programming capability, dedicated mRNA secondary structure prediction, artificial neural network modeling, network & multi-threaded computing, and user-accessible programming modules. The software allows a user to analyze and optimize a sequence using main menu functions or specialized module windows. Alternatively, gene optimization can be initiated by designing a gene construct and configuring an optimization strategy. A user can choose several predefined or user-defined algorithms to design a complicated strategy. The software provides expandable functionality as platform software supporting module development using popular script languages such as VBScript and JScript in the software programming environment. Visual Gene Developer is useful for both researchers who want to quickly analyze and optimize genes, and those who are interested in developing and testing new algorithms in bioinformatics. The software is available for free download at http://www.visualgenedeveloper.net.

Underwater Photo-Elicitation: A New Experiential Marine Education Technique

ERIC Educational Resources Information Center

Andrews, Steve; Stocker, Laura; Oechel, Walter

2018-01-01

Underwater photo-elicitation is a novel experiential marine education technique that combines direct experience in the marine environment with the use of digital underwater cameras. A program called Show Us Your Ocean! (SUYO!) was created, utilising a mixed methodology (qualitative and quantitative methods) to test the efficacy of this technique.…

Computational Support for Early Elicitation and Classification of Tone

ERIC Educational Resources Information Center

Bird, Steven; Lee, Haejoong

2014-01-01

Investigating a tone language involves careful transcription of tone on words and phrases. This is challenging when the phonological categories--the tones or melodies--have not been identified. Effects such as coarticulation, sandhi, and phrase-level prosody appear as obstacles to early elicitation and classification of tone. This article presents…

Photo-Elicitation Method Gives Voice and Reactions of Subjects.

ERIC Educational Resources Information Center

Smith, C. Zoe; Woodward, Anne-Marie

1999-01-01

Describes a research assignment (called "photo-elicitation") in a graduate course on the role of photography in society in which students interview people similar to the subjects in the photographs to discover how the photographs affect them. Includes material from one research project interviewing three recovering drug addicts responding to Larry…

HMGA2 elicits EMT by activating the Wnt/β-catenin pathway in gastric cancer.

PubMed

Zha, Lang; Zhang, Jing; Tang, Weixue; Zhang, Neng; He, Miao; Guo, Yi; Wang, Ziwei

2013-03-01

The high mobility group protein A2 (HMGA2) is an architectural transcription factor that plays an important role in the development and progression of many malignant neoplasms. High expression of HMGA2 in gastric cancer correlates with invasiveness of cancer and is an independent prognostic factor. The reason for this might be HMGA2 promoting epithelial-mesenchymal transitions (EMT), which is the key process of metastasis for some underlying mechanisms. This study was designed to test whether HMGA2 participates in the EMT and to further understand the underlying mechanisms of EMT promoted by HMGA2. We examined the cell biology and molecular biology changes after overexpression and knockdown HMGA2 of gastric cancer cells in vitro and vivo. To further understand the underlying mechanisms of EMT promoted by HMGA2, based on our previous study, we examined the changes of target genes of HMGA2 after overexpression and knockdown HMGA2 of gastric cancer cells. The results indicated that overexpressing HMGA2 enabled enhancing the oncogenic properties of gastric epithelial origin cell in vitro and in vivo. Furthermore, our study showed that HMGA2 was able to elicit EMT and regulate several genes which are closely related to the Wnt/β-catenin pathway by directly binding to their promoter thereby activating the Wnt/β-catenin pathway. The Wnt/β-catenin pathway activated by HMGA2 might be the underlying mechanism of EMT in gastric cancer cells.

A Step-Wise Approach to Elicit Triangular Distributions

NASA Technical Reports Server (NTRS)

Greenberg, Marc W.

2013-01-01

Adapt/combine known methods to demonstrate an expert judgment elicitation process that: 1.Models expert's inputs as a triangular distribution, 2.Incorporates techniques to account for expert bias and 3.Is structured in a way to help justify expert's inputs. This paper will show one way of "extracting" expert opinion for estimating purposes. Nevertheless, as with most subjective methods, there are many ways to do this.

9-methoxycanthin-6-one production in elicited hairy roots culture of Eurycoma longifolia

NASA Astrophysics Data System (ADS)

Abdullah, Nazirah; Ismail, Ismanizan; Hassan, Nor Hasnida; Basherudin, Norlia

2016-11-01

Eurycoma longifolia (Tongkat Ali) is a highly sought after medicinal plant in Malaysia. Propagation of E. longifolia through tissue culture has been reported in order to cater the industry demands for planting and raw materials as well as for conservation purposes. E. longifolia hairy roots culture has been developed using Agrobacterium rhizogenes for the production of Tongkat Ali phytochemicals. Effects of three elicitors; methyl jasmonate, salicylic acid, and yeast extract at different concentrations were evaluated on the production of 9-methoxycanthin-6-one in E. longifolia hairy roots. The cultures were elicited at early exponential growth phase, followed by extraction of 9-methoxycanthin-6-one using methanol and HPLC analysis. Elicitation with methyl jasmonate at all concentrations increased 9-methoxycanthin-6-one up to 1-3 fold and treatment with (0.1 mM) was most efficient in enhancing 9-methoxycanthin-6-one production up to 3.902 mg/g dry weight after 7 days (168 hours) elicitation.

Finding pathway-modulating genes from a novel Ontology Fingerprint-derived gene network

PubMed Central

Qin, Tingting; Matmati, Nabil; Tsoi, Lam C.; Mohanty, Bidyut K.; Gao, Nan; Tang, Jijun; Lawson, Andrew B.; Hannun, Yusuf A.; Zheng, W. Jim

2014-01-01

To enhance our knowledge regarding biological pathway regulation, we took an integrated approach, using the biomedical literature, ontologies, network analyses and experimental investigation to infer novel genes that could modulate biological pathways. We first constructed a novel gene network via a pairwise comparison of all yeast genes’ Ontology Fingerprints—a set of Gene Ontology terms overrepresented in the PubMed abstracts linked to a gene along with those terms’ corresponding enrichment P-values. The network was further refined using a Bayesian hierarchical model to identify novel genes that could potentially influence the pathway activities. We applied this method to the sphingolipid pathway in yeast and found that many top-ranked genes indeed displayed altered sphingolipid pathway functions, initially measured by their sensitivity to myriocin, an inhibitor of de novo sphingolipid biosynthesis. Further experiments confirmed the modulation of the sphingolipid pathway by one of these genes, PFA4, encoding a palmitoyl transferase. Comparative analysis showed that few of these novel genes could be discovered by other existing methods. Our novel gene network provides a unique and comprehensive resource to study pathway modulations and systems biology in general. PMID:25063300

Identification of Single- and Multiple-Class Specific Signature Genes from Gene Expression Profiles by Group Marker Index

PubMed Central

Tsai, Yu-Shuen; Aguan, Kripamoy; Pal, Nikhil R.; Chung, I-Fang

2011-01-01

Informative genes from microarray data can be used to construct prediction model and investigate biological mechanisms. Differentially expressed genes, the main targets of most gene selection methods, can be classified as single- and multiple-class specific signature genes. Here, we present a novel gene selection algorithm based on a Group Marker Index (GMI), which is intuitive, of low-computational complexity, and efficient in identification of both types of genes. Most gene selection methods identify only single-class specific signature genes and cannot identify multiple-class specific signature genes easily. Our algorithm can detect de novo certain conditions of multiple-class specificity of a gene and makes use of a novel non-parametric indicator to assess the discrimination ability between classes. Our method is effective even when the sample size is small as well as when the class sizes are significantly different. To compare the effectiveness and robustness we formulate an intuitive template-based method and use four well-known datasets. We demonstrate that our algorithm outperforms the template-based method in difficult cases with unbalanced distribution. Moreover, the multiple-class specific genes are good biomarkers and play important roles in biological pathways. Our literature survey supports that the proposed method identifies unique multiple-class specific marker genes (not reported earlier to be related to cancer) in the Central Nervous System data. It also discovers unique biomarkers indicating the intrinsic difference between subtypes of lung cancer. We also associate the pathway information with the multiple-class specific signature genes and cross-reference to published studies. We find that the identified genes participate in the pathways directly involved in cancer development in leukemia data. Our method gives a promising way to find genes that can involve in pathways of multiple diseases and hence opens up the possibility of using an existing

Deep sequencing reveals unique small RNA repertoire that is regulated during head regeneration in Hydra magnipapillata.

PubMed

Krishna, Srikar; Nair, Aparna; Cheedipudi, Sirisha; Poduval, Deepak; Dhawan, Jyotsna; Palakodeti, Dasaradhi; Ghanekar, Yashoda

2013-01-07

Small non-coding RNAs such as miRNAs, piRNAs and endo-siRNAs fine-tune gene expression through post-transcriptional regulation, modulating important processes in development, differentiation, homeostasis and regeneration. Using deep sequencing, we have profiled small non-coding RNAs in Hydra magnipapillata and investigated changes in small RNA expression pattern during head regeneration. Our results reveal a unique repertoire of small RNAs in hydra. We have identified 126 miRNA loci; 123 of these miRNAs are unique to hydra. Less than 50% are conserved across two different strains of Hydra vulgaris tested in this study, indicating a highly diverse nature of hydra miRNAs in contrast to bilaterian miRNAs. We also identified siRNAs derived from precursors with perfect stem-loop structure and that arise from inverted repeats. piRNAs were the most abundant small RNAs in hydra, mapping to transposable elements, the annotated transcriptome and unique non-coding regions on the genome. piRNAs that map to transposable elements and the annotated transcriptome display a ping-pong signature. Further, we have identified several miRNAs and piRNAs whose expression is regulated during hydra head regeneration. Our study defines different classes of small RNAs in this cnidarian model system, which may play a role in orchestrating gene expression essential for hydra regeneration.

Deep sequencing reveals unique small RNA repertoire that is regulated during head regeneration in Hydra magnipapillata

PubMed Central

Krishna, Srikar; Nair, Aparna; Cheedipudi, Sirisha; Poduval, Deepak; Dhawan, Jyotsna; Palakodeti, Dasaradhi; Ghanekar, Yashoda

2013-01-01

Small non-coding RNAs such as miRNAs, piRNAs and endo-siRNAs fine-tune gene expression through post-transcriptional regulation, modulating important processes in development, differentiation, homeostasis and regeneration. Using deep sequencing, we have profiled small non-coding RNAs in Hydra magnipapillata and investigated changes in small RNA expression pattern during head regeneration. Our results reveal a unique repertoire of small RNAs in hydra. We have identified 126 miRNA loci; 123 of these miRNAs are unique to hydra. Less than 50% are conserved across two different strains of Hydra vulgaris tested in this study, indicating a highly diverse nature of hydra miRNAs in contrast to bilaterian miRNAs. We also identified siRNAs derived from precursors with perfect stem–loop structure and that arise from inverted repeats. piRNAs were the most abundant small RNAs in hydra, mapping to transposable elements, the annotated transcriptome and unique non-coding regions on the genome. piRNAs that map to transposable elements and the annotated transcriptome display a ping–pong signature. Further, we have identified several miRNAs and piRNAs whose expression is regulated during hydra head regeneration. Our study defines different classes of small RNAs in this cnidarian model system, which may play a role in orchestrating gene expression essential for hydra regeneration. PMID:23166307

Unique Features of the Loblolly Pine (Pinus taeda L.) Megagenome Revealed Through Sequence Annotation

PubMed Central

Wegrzyn, Jill L.; Liechty, John D.; Stevens, Kristian A.; Wu, Le-Shin; Loopstra, Carol A.; Vasquez-Gross, Hans A.; Dougherty, William M.; Lin, Brian Y.; Zieve, Jacob J.; Martínez-García, Pedro J.; Holt, Carson; Yandell, Mark; Zimin, Aleksey V.; Yorke, James A.; Crepeau, Marc W.; Puiu, Daniela; Salzberg, Steven L.; de Jong, Pieter J.; Mockaitis, Keithanne; Main, Doreen; Langley, Charles H.; Neale, David B.

2014-01-01

The largest genus in the conifer family Pinaceae is Pinus, with over 100 species. The size and complexity of their genomes (∼20–40 Gb, 2n = 24) have delayed the arrival of a well-annotated reference sequence. In this study, we present the annotation of the first whole-genome shotgun assembly of loblolly pine (Pinus taeda L.), which comprises 20.1 Gb of sequence. The MAKER-P annotation pipeline combined evidence-based alignments and ab initio predictions to generate 50,172 gene models, of which 15,653 are classified as high confidence. Clustering these gene models with 13 other plant species resulted in 20,646 gene families, of which 1554 are predicted to be unique to conifers. Among the conifer gene families, 159 are composed exclusively of loblolly pine members. The gene models for loblolly pine have the highest median and mean intron lengths of 24 fully sequenced plant genomes. Conifer genomes are full of repetitive DNA, with the most significant contributions from long-terminal-repeat retrotransposons. In depth analysis of the tandem and interspersed repetitive content yielded a combined estimate of 82%. PMID:24653211

Photo-Elicitation: Reflexivity on Method, Analysis, and Graphic Portraits

ERIC Educational Resources Information Center

Richard, Veronica M.; Lahman, Maria K. E.

2015-01-01

In this methodological discussion, the authors detail and reflect on the processes of using photo-elicitation interviewing as a way to align with positive qualitative methodologies, to gain access to participant beliefs and values, and to highlight participant voices through their choices of words and visuals. A review of the literature and an…

Forest gene conservation programs in Alberta, Canada

Treesearch

Jodie Krakowski

2017-01-01

Provincial tree improvement programs in Alberta began in 1976. Early gene conservation focused on ex situ measures such as seed and clone banking, and research trials of commercial species with tree improvement programs. The gene conservation program now encompasses representative and unique populations of all native tree species in situ. The ex situ program aims to...

Choose, rate or squeeze: Comparison of economic value functions elicited by different behavioral tasks

PubMed Central

Pessiglione, Mathias

2017-01-01

A standard view in neuroeconomics is that to make a choice, an agent first assigns subjective values to available options, and then compares them to select the best. In choice tasks, these cardinal values are typically inferred from the preference expressed by subjects between options presented in pairs. Alternatively, cardinal values can be directly elicited by asking subjects to place a cursor on an analog scale (rating task) or to exert a force on a power grip (effort task). These tasks can vary in many respects: they can notably be more or less costly and consequential. Here, we compared the value functions elicited by choice, rating and effort tasks on options composed of two monetary amounts: one for the subject (gain) and one for a charity (donation). Bayesian model selection showed that despite important differences between the three tasks, they all elicited a same value function, with similar weighting of gain and donation, but variable concavity. Moreover, value functions elicited by the different tasks could predict choices with equivalent accuracy. Our finding therefore suggests that comparable value functions can account for various motivated behaviors, beyond economic choice. Nevertheless, we report slight differences in the computational efficiency of parameter estimation that may guide the design of future studies. PMID:29161252

Dominant Lyapunov exponent and approximate entropy in heart rate variability during emotional visual elicitation

PubMed Central

Valenza, Gaetano; Allegrini, Paolo; Lanatà, Antonio; Scilingo, Enzo Pasquale

2012-01-01

In this work we characterized the non-linear complexity of Heart Rate Variability (HRV) in short time series. The complexity of HRV signal was evaluated during emotional visual elicitation by using Dominant Lyapunov Exponents (DLEs) and Approximate Entropy (ApEn). We adopted a simplified model of emotion derived from the Circumplex Model of Affects (CMAs), in which emotional mechanisms are conceptualized in two dimensions by the terms of valence and arousal. Following CMA model, a set of standardized visual stimuli in terms of arousal and valence gathered from the International Affective Picture System (IAPS) was administered to a group of 35 healthy volunteers. Experimental session consisted of eight sessions alternating neutral images with high arousal content images. Several works can be found in the literature showing a chaotic dynamics of HRV during rest or relax conditions. The outcomes of this work showed a clear switching mechanism between regular and chaotic dynamics when switching from neutral to arousal elicitation. Accordingly, the mean ApEn decreased with statistical significance during arousal elicitation and the DLE became negative. Results showed a clear distinction between the neutral and the arousal elicitation and could be profitably exploited to improve the accuracy of emotion recognition systems based on HRV time series analysis. PMID:22393320

Good Food, Bad Food, and White Rice: Understanding Child Feeding Using Visual-Narrative Elicitation.

PubMed

Wentworth, Chelsea

2017-01-01

Visual-narrative elicitation, a process combining photo elicitation and pile sorting in applied medical anthropology, sheds light on food consumption patterns in urban areas of Vanuatu where childhood malnutrition is a persistent problem. Groups of participants took photographs of the foods they feed their children, and the resources and barriers they encounter in accessing foodstuffs. This revealed how imported and local foods are assigned value as "good" or "bad" foods when contributing to dietary diversity and creating appropriate meals for children, particularly in the context of consuming white rice. The process of gathering and working with photographs illuminated the complex negotiations in which caregivers engaged when making food and nutritional choices for their children. At the nexus of visual and medical anthropology, the visual-narrative elicitation process yielded nuanced, comprehensive understandings of how caregivers value the various foods they feed their children.

Augmenting Usability: Cultural Elicitation in HCI

NASA Astrophysics Data System (ADS)

Camara, Souleymane Boundaouda; Oyugi, Cecilia; Abdelnour-Nocera, José; Smith, Andy

This paper offers context and culture elicitation in an inter-cultural and multi-disciplinary setting of ICT design. Localised usability evaluation (LUE) is augmented with a socio-technical evaluation tool (STEM) as a methodological approach to expose and address issues in a collaborative ICT design within the Village e-Science for Life (VeSeL) project in rural Kenya. The paper argues that designers need to locally identify context and culture in situ and further explicate their implications through the design process and at the global level. Stakeholders' context, culture, decisions, agendas, expectations, disciplines and requirements need to be locally identified and globally evaluated to ensure a fit for purpose solution.

STAT3 Target Genes Relevant to Human Cancers

PubMed Central

Carpenter, Richard L.; Lo, Hui-Wen

2014-01-01

Since its discovery, the STAT3 transcription factor has been extensively studied for its function as a transcriptional regulator and its role as a mediator of development, normal physiology, and pathology of many diseases, including cancers. These efforts have uncovered an array of genes that can be positively and negatively regulated by STAT3, alone and in cooperation with other transcription factors. Through regulating gene expression, STAT3 has been demonstrated to play a pivotal role in many cellular processes including oncogenesis, tumor growth and progression, and stemness. Interestingly, recent studies suggest that STAT3 may behave as a tumor suppressor by activating expression of genes known to inhibit tumorigenesis. Additional evidence suggested that STAT3 may elicit opposing effects depending on cellular context and tumor types. These mixed results signify the need for a deeper understanding of STAT3, including its upstream regulators, parallel transcription co-regulators, and downstream target genes. To help facilitate fulfilling this unmet need, this review will be primarily focused on STAT3 downstream target genes that have been validated to associate with tumorigenesis and/or malignant biology of human cancers. PMID:24743777

Chronic molindone treatment: relative inability to elicit dopamine receptor supersensitivity in rats.

PubMed

Meller, E

1982-01-01

Chronic treatment of rats with the antipsychotic drug molindone (2.5 mg/kg) did not elicit behavioral supersensitivity to apomorphine (AP) (0.25 mg/kg) or increased striatal 3H-spiroperidol binding, whereas treatment with haloperidol (0.5-1.0 mg/kg) produced manifestations of dopaminergic supersensitivity in both paradigms. Chronic treatment with a high dose of molindone (20 mg/kg) elicited a small, but significant increase in behavioral sensitivity to AP (57%) which was, however, significantly less than that produced by 1 mg/kg haloperidol (126%, P less than 0.01). Apparent tolerance to elevation of striatal and frontal cortical 3,4-dihydroxyphenylacetic acid (DOPAC) levels was obtained with chronic molindone treatment (5 or 20 mg/kg). None of the molindone doses used (2.5-50 mg/kg) increased striatal dopamine receptor binding. Scatchard analyses revealed no change in either maximal binding capacity (Bmax) or dissociation constant (Kd). A significant (P less than 0.001) correlation of receptor binding activity and stereotypy score was obtained for haloperidol-, but not molindone-treated rats. These results with molindone in an animal model of tardive dyskinesia suggest that this drug may have a lower potential for eliciting this disorder in humans.

Elicitation of neurological knowledge with argument-based machine learning.

PubMed

Groznik, Vida; Guid, Matej; Sadikov, Aleksander; Možina, Martin; Georgiev, Dejan; Kragelj, Veronika; Ribarič, Samo; Pirtošek, Zvezdan; Bratko, Ivan

2013-02-01

The paper describes the use of expert's knowledge in practice and the efficiency of a recently developed technique called argument-based machine learning (ABML) in the knowledge elicitation process. We are developing a neurological decision support system to help the neurologists differentiate between three types of tremors: Parkinsonian, essential, and mixed tremor (comorbidity). The system is intended to act as a second opinion for the neurologists, and most importantly to help them reduce the number of patients in the "gray area" that require a very costly further examination (DaTSCAN). We strive to elicit comprehensible and medically meaningful knowledge in such a way that it does not come at the cost of diagnostic accuracy. To alleviate the difficult problem of knowledge elicitation from data and domain experts, we used ABML. ABML guides the expert to explain critical special cases which cannot be handled automatically by machine learning. This very efficiently reduces the expert's workload, and combines expert's knowledge with learning data. 122 patients were enrolled into the study. The classification accuracy of the final model was 91%. Equally important, the initial and the final models were also evaluated for their comprehensibility by the neurologists. All 13 rules of the final model were deemed as appropriate to be able to support its decisions with good explanations. The paper demonstrates ABML's advantage in combining machine learning and expert knowledge. The accuracy of the system is very high with respect to the current state-of-the-art in clinical practice, and the system's knowledge base is assessed to be very consistent from a medical point of view. This opens up the possibility to use the system also as a teaching tool. Copyright © 2012 Elsevier B.V. All rights reserved.

Three-Dimensional Gene Map of Cancer Cell Types: Structural Entropy Minimisation Principle for Defining Tumour Subtypes

PubMed Central

Li, Angsheng; Yin, Xianchen; Pan, Yicheng

2016-01-01

In this study, we propose a method for constructing cell sample networks from gene expression profiles, and a structural entropy minimisation principle for detecting natural structure of networks and for identifying cancer cell subtypes. Our method establishes a three-dimensional gene map of cancer cell types and subtypes. The identified subtypes are defined by a unique gene expression pattern, and a three-dimensional gene map is established by defining the unique gene expression pattern for each identified subtype for cancers, including acute leukaemia, lymphoma, multi-tissue, lung cancer and healthy tissue. Our three-dimensional gene map demonstrates that a true tumour type may be divided into subtypes, each defined by a unique gene expression pattern. Clinical data analyses demonstrate that most cell samples of an identified subtype share similar survival times, survival indicators and International Prognostic Index (IPI) scores and indicate that distinct subtypes identified by our algorithms exhibit different overall survival times, survival ratios and IPI scores. Our three-dimensional gene map establishes a high-definition, one-to-one map between the biologically and medically meaningful tumour subtypes and the gene expression patterns, and identifies remarkable cells that form singleton submodules. PMID:26842724

Pre-Service Teachers' Modelling Processes through Engagement with Model Eliciting Activities with a Technological Tool

ERIC Educational Resources Information Center

Daher, Wajeeh M.; Shahbari, Juhaina Awawdeh

2015-01-01

Engaging mathematics students with modelling activities helps them learn mathematics meaningfully. This engagement, in the case of model eliciting activities, helps the students elicit mathematical models by interpreting real-world situation in mathematical ways. This is especially true when the students utilize technology to build the models.…

Lafora disease offers a unique window into neuronal glycogen metabolism.

PubMed

Gentry, Matthew S; Guinovart, Joan J; Minassian, Berge A; Roach, Peter J; Serratosa, Jose M

2018-05-11

Lafora disease (LD) is a fatal, autosomal recessive, glycogen-storage disorder that manifests as severe epilepsy. LD results from mutations in the gene encoding either the glycogen phosphatase laforin or the E3 ubiquitin ligase malin. Individuals with LD develop cytoplasmic, aberrant glycogen inclusions in nearly all tissues that more closely resemble plant starch than human glycogen. This Minireview discusses the unique window into glycogen metabolism that LD research offers. It also highlights recent discoveries, including that glycogen contains covalently bound phosphate and that neurons synthesize glycogen and express both glycogen synthase and glycogen phosphorylase. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Unique cerebrovascular anomalies in Noonan syndrome with RAF1 mutation.

PubMed

Zarate, Yuri A; Lichty, Angie W; Champion, Kristen J; Clarkson, L Kate; Holden, Kenton R; Matheus, M Gisele

2014-08-01

Noonan syndrome is a common autosomal dominant neurodevelopmental disorder caused by gain-of-function germline mutations affecting components of the Ras-MAPK pathway. The authors present the case of a 6-year-old male with Noonan syndrome, Chiari malformation type I, shunted benign external hydrocephalus in infancy, and unique cerebrovascular changes. A de novo heterozygous change in the RAF1 gene was identified. The patient underwent brain magnetic resonance imaging, computed tomography angiography, and magnetic resonance angiography to further clarify the nature of his abnormal brain vasculature. The authors compared his findings to the few cases of Noonan syndrome reported with cerebrovascular pathology. © The Author(s) 2013.

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface.

PubMed

Bukowski, Radek; Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M; Andrews, William; Saade, George R; Ilekis, John V; Reddy, Uma M; Baldwin, Donald A

2017-01-01

Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment ( n  = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL ( n  = 8), PNL ( n  = 10), TL ( n  = 7) and TNL ( n  = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene's 5' promoter or 3'-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in

Finding pathway-modulating genes from a novel Ontology Fingerprint-derived gene network.

PubMed

Qin, Tingting; Matmati, Nabil; Tsoi, Lam C; Mohanty, Bidyut K; Gao, Nan; Tang, Jijun; Lawson, Andrew B; Hannun, Yusuf A; Zheng, W Jim

2014-10-01

To enhance our knowledge regarding biological pathway regulation, we took an integrated approach, using the biomedical literature, ontologies, network analyses and experimental investigation to infer novel genes that could modulate biological pathways. We first constructed a novel gene network via a pairwise comparison of all yeast genes' Ontology Fingerprints--a set of Gene Ontology terms overrepresented in the PubMed abstracts linked to a gene along with those terms' corresponding enrichment P-values. The network was further refined using a Bayesian hierarchical model to identify novel genes that could potentially influence the pathway activities. We applied this method to the sphingolipid pathway in yeast and found that many top-ranked genes indeed displayed altered sphingolipid pathway functions, initially measured by their sensitivity to myriocin, an inhibitor of de novo sphingolipid biosynthesis. Further experiments confirmed the modulation of the sphingolipid pathway by one of these genes, PFA4, encoding a palmitoyl transferase. Comparative analysis showed that few of these novel genes could be discovered by other existing methods. Our novel gene network provides a unique and comprehensive resource to study pathway modulations and systems biology in general. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Pretreatment of Parsley (Petroselinum crispum L.) Suspension Cultures with Methyl Jasmonate Enhances Elicitation of Activated Oxygen Species.

PubMed Central

Kauss, H.; Jeblick, W.; Ziegler, J.; Krabler, W.

1994-01-01

Suspension-cultured cells of parsley (Petroselinum crispum L.) were used to demonstrate an influence of jasmonic acid methyl ester (JAME) on the elicitation of activated oxygen species. Preincubation of the cell cultures for 1 d with JAME greatly enhanced the subsequent induction by an elicitor preparation from cell walls of Phytophtora megasperma f. sp. glycinea (Pmg elicitor) and by the polycation chitosan. Shorter preincubation times with JAME were less efficient, and the effect was saturated at about 5 [mu]M JAME. Treatment of the crude Pmg elicitor with trypsin abolished induction of activated oxygen species, an effect similar to that seen with elicitation of coumarin secretion. These results suggest that JAME conditioned the parsley suspension cells in a time-dependent manner to become more responsive to elicitation, reminiscent of developmental effects caused by JAME in whole plants. It is interesting that pretreatment of the parsley cultures with 2,6-dichloroisonicotinic and 5-chlorosalicylic acid only slightly enhanced the elicitation of activated oxygen species, whereas these substances greatly enhanced the elicitation of coumarin secretion. Therefore, these presumed inducers of systemic acquired resistance exhibit a specificity different from JAME. PMID:12232189

Effect of jasmonic acid and yeast extract elicitation on low-molecular antioxidants and antioxidant activity of marjoram (Origanum majorana L.).

PubMed

Złotek, Urszula

2017-01-01

Elicitation, which is a way of inducing plant secondary metabolism, may be an effective method for improving the quality of plant food. The aim of this study was to determine how the application of jasmonic acid (as an abiotic elicitor) and yeast extract (as a biotic elicitor) influences the production of some bioactive compounds in marjoram and the antioxidant activity of this herb. Elicitation with 0.01 µM and 1 µM jasmonic acid as well as 0.1% and 1% yeast extracts was used for improving the health-benefiting quality of marjoram. The study focused on the effects of eliciting the level of some phytochemicals and the antioxidant activity of marjoram. There were no significant differences in total phenolic content between the elicited and control plants. In turn, the elicitation with 0.1% and 1% yeast extracts caused 1.8- and 2.5-fold increases in the ascorbic acid content in marjoram leaves, respectively. Both biotic and abiotic elicitation resulted in elevation of chlorophyll content, but only the abiotic elicitor (jasmonic acid) caused a significant increase (by over 50%) in the carotenoid content of marjoram leaves. The antiradical activity of marjoram was increased by the abiotic and biotic elicitation, whereas only the abiotic elicitation resulted in improving the reducing power of this herb. In conclusion, biotic and abiotic elicitation could be an effective strategy for improving the level of some phytochemicals, as well as the antioxidant activity of marjoram. A particularly valuable finding obtained in this study is that natural elicitors e.g. yeast extract can be equally effective in elevating the content of some bioactive compounds in herbs e.g. marjoram as an abiotic one.

FUNCTIONAL NANOPARTICLES FOR MOLECULAR IMAGING GUIDED GENE DELIVERY

PubMed Central

Liu, Gang; Swierczewska, Magdalena; Lee, Seulki; Chen, Xiaoyuan

2010-01-01

Gene therapy has great potential to bring tremendous changes in treatment of various diseases and disorders. However, one of the impediments to successful gene therapy is the inefficient delivery of genes to target tissues and the inability to monitor delivery of genes and therapeutic responses at the targeted site. The emergence of molecular imaging strategies has been pivotal in optimizing gene therapy; since it can allow us to evaluate the effectiveness of gene delivery noninvasively and spatiotemporally. Due to the unique physiochemical properties of nanomaterials, numerous functional nanoparticles show promise in accomplishing gene delivery with the necessary feature of visualizing the delivery. In this review, recent developments of nanoparticles for molecular imaging guided gene delivery are summarized. PMID:22473061

Expression of a highly basic peroxidase gene in NaCl-adapted tomato cell suspensions.

PubMed

Medina, M I; Botella, M A; Quesada, M A; Valpuesta, V

1997-05-05

A tomato peroxidase gene, TPX2, that is only weakly expressed in the roots of young tomato seedlings is highly expressed in tomato suspension cells adapted to high external NaCl concentration. The protein encoded by this gene, with an isolectric point value of approximately 9.6, is found in the culture medium of the growing cells. Our data suggest that the expression of TPX2 in the salt-adapted cells is not the result of the elicitation imposed by the in vitro culture or the presence of high NaCl concentration in the medium.

Visual gene developer: a fully programmable bioinformatics software for synthetic gene optimization

PubMed Central

2011-01-01

Background Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. Results The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interface, but also includes unique features such as programming capability, dedicated mRNA secondary structure prediction, artificial neural network modeling, network & multi-threaded computing, and user-accessible programming modules. The software allows a user to analyze and optimize a sequence using main menu functions or specialized module windows. Alternatively, gene optimization can be initiated by designing a gene construct and configuring an optimization strategy. A user can choose several predefined or user-defined algorithms to design a complicated strategy. The software provides expandable functionality as platform software supporting module development using popular script languages such as VBScript and JScript in the software programming environment. Conclusion Visual Gene Developer is useful for both researchers who want to quickly analyze and optimize genes, and those who are interested in developing and testing new algorithms in bioinformatics. The software is available for free download at http://www.visualgenedeveloper.net. PMID:21846353

Multidrug resistance in fungi: regulation of transporter-encoding gene expression

PubMed Central

Paul, Sanjoy; Moye-Rowley, W. Scott

2014-01-01

A critical risk to the continued success of antifungal chemotherapy is the acquisition of resistance; a risk exacerbated by the few classes of effective antifungal drugs. Predictably, as the use of these drugs increases in the clinic, more resistant organisms can be isolated from patients. A particularly problematic form of drug resistance that routinely emerges in the major fungal pathogens is known as multidrug resistance. Multidrug resistance refers to the simultaneous acquisition of tolerance to a range of drugs via a limited or even single genetic change. This review will focus on recent progress in understanding pathways of multidrug resistance in fungi including those of most medical relevance. Analyses of multidrug resistance in Saccharomyces cerevisiae have provided the most detailed outline of multidrug resistance in a eukaryotic microorganism. Multidrug resistant isolates of S. cerevisiae typically result from changes in the activity of a pair of related transcription factors that in turn elicit overproduction of several target genes. Chief among these is the ATP-binding cassette (ABC)-encoding gene PDR5. Interestingly, in the medically important Candida species, very similar pathways are involved in acquisition of multidrug resistance. In both C. albicans and C. glabrata, changes in the activity of transcriptional activator proteins elicits overproduction of a protein closely related to S. cerevisiae Pdr5 called Cdr1. The major filamentous fungal pathogen, Aspergillus fumigatus, was previously thought to acquire resistance to azole compounds (the principal antifungal drug class) via alterations in the azole drug target-encoding gene cyp51A. More recent data indicate that pathways in addition to changes in the cyp51A gene are important determinants in A. fumigatus azole resistance. We will discuss findings that suggest azole resistance in A. fumigatus and Candida species may share more mechanistic similarities than previously thought. PMID:24795641

Consanguinity in Saudi Arabia: a unique opportunity for pediatric kidney research.

PubMed

Kari, Jameela A; Bockenhauer, Detlef; Stanescu, Horia; Gari, Mamdooh; Kleta, Robert; Singh, Ajay K

2014-02-01

Identification of disease-related genes is a critical step in understanding the molecular basis of disease and developing targeted therapies. The genetic study of diseases occurring in the offspring of consanguineous unions is a powerful way to discover new disease genes. Pediatric nephrology provides an excellent example because ∼70% of cases of kidney disease in childhood are congenital with a likely genetic basis. This percentage is likely to be even higher in countries with a high consanguinity rate, such as the Kingdom of Saudi Arabia. However, there are a number of challenges, such as cultural, legal, and religious restrictions, that should be appreciated before carrying out genetic research in a tradition-bound country. In this article, we discuss the background, opportunities, and challenges involved with this unique opportunity to conduct studies of such genetic disorders. Keys to success include collaboration and an understanding of local traditions and laws. Copyright © 2014 National Kidney Foundation, Inc. All rights reserved.

Transcriptome analysis of Pacific white shrimp (Litopenaeus vannamei) challenged by Vibrio parahaemolyticus reveals unique immune-related genes.

PubMed

Qin, Zhendong; Babu, V Sarath; Wan, Quanyuan; Zhou, Meng; Liang, Risheng; Muhammad, Asim; Zhao, Lijuan; Li, Jun; Lan, Jiangfeng; Lin, Li

2018-06-01

Pacific white shrimp (Litopenaeus vannamei) is an important cultural species worldwide. However, Vibrio spp. infections have caused a great economic loss in Pacific white shrimp culture industry. The immune responses of Pacific white shrimp to the Vibrio spp. is not fully characterized. In this study, the transcriptomic profiles of L. vannamei hemocytes were explored by injecting with or without Vibrio parahaemolyticus. Totally, 42,632 high-quality unigenes were obtained from RNAseq data. Comparative genome analysis showed 2258 differentially expressed genes (DEGs) following the Vibrio challenge, including 1017 up-regulated and 1241 down-regulated genes. Eight DEGs were randomly selected for further validation by quantitative real-time RT-PCR (qRT-PCR) and the results showed that are consistent with the RNA-seq data. Due to the lack of predictable adaptive immunity, shrimps rely on an innate immune system to defend themselves against invading microbes by recognizing and clearing them through humoral and cellular immune responses. Here we focused our studies on the humoral immunity, five genes (SR, MNK, CTL3, GILT, and ALFP) were selected from the transcriptomic data, which were significantly up-regulated by V. parahaemolyticus infection. These genes were widely expressed in six different tissues and were up-regulated by both Gram negative bacteria (V. parahaemolyticus) and Gram positive bacteria (Staphylococcus aureus). To further extend our studies, we knock-down those five genes by dsRNA in L. vannamei and analyzed the functions of specific genes against V. parahaemolyticus and S. aureus by bacterial clearance analysis. We found that the ability of L. vannamei was significantly reduced in bacterial clearance when treated with those specific dsRNA. These results indicate that those five genes play essential roles in antibacterial immunity and have its specific functions against different types of pathogens. The obtained data will shed a new light on the immunity

Eliciting Values of Patients with Multiple Chronic Conditions: Evaluation of a Patient-centered Framework.

PubMed

Berry, Andrew B L; Lim, Catherine; Hartzler, Andrea L; Hirsch, Tad; Ludman, Evette; Wagner, Edward H; Ralston, James D

2017-01-01

Patients with multiple chronic conditions often face competing demands for care, and they often do not agree with physicians on priorities for care. Patients ' values shape their healthcare priorities, but existing methods for eliciting values do not necessarily meet patients ' care planning needs. We developed a patient-centered values framework based on a field study with patients and caregivers. In this paper we report on a survey to evaluate how the framework generalizes beyond field study participants, and how well the framework supports values elicitation. We found that respondents frame values in a way that is consistent with the framework, and that domains of the framework can be used to elicit a breadth of potential values individuals with MCC express. These findings demonstrate how a patient-centered perspective on values can expand on the domains considered in values clarification methods andfacilitate patient-provider communication in establishing shared care priorities.

Cytotoxicity, genotoxicity and gene expression changes elicited by exposure of human hepatic cells to Ginkgo biloba leaf extract.

PubMed

Grollino, Maria Giuseppa; Raschellà, Giuseppe; Cordelli, Eugenia; Villani, Paola; Pieraccioli, Marco; Paximadas, Irene; Malandrino, Salvatore; Bonassi, Stefano; Pacchierotti, Francesca

2017-11-01

The use of Ginkgo biloba leaf extract as nutraceutical is becoming increasingly common. As a consequence, the definition of a reliable toxicological profile is a priority for its safe utilization. Recently, contrasting data have been reported on the carcinogenic potential of Ginkgo biloba extract in rodent liver. We measured viability, Reactive Oxygen Species (ROS), apoptosis, colony-forming efficiency, genotoxicity by comet assay, and gene expression changes associated with hepato-carcinogenicity in human cells of hepatic origin (HepG2 and THLE-2) treated with different concentrations (0.0005-1.2 mg/mL) of Ginkgoselect ® Plus. Our analyses highlighted a decrease of cell viability, not due to apoptosis, after treatment with high doses of the extract, which was likely due to ROS generation by a chemical reaction between extract polyphenols and some components of the culture medium. Comet assay did not detect genotoxic effect at any extract concentration. Finally, the array analysis detected a slight decrease in the expression of only one gene (IGFBP3) in Ginkgo-treated THLE-2 cells as opposed to changes in 28 genes in Aflatoxin B1 treated-cells. In conclusion, our results did not detect any significant genotoxic or biologically relevant cytotoxic effects and gross changes in gene expression using the Ginkgo extract in the hepatic cells tested. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate (17-OHPC), and related progestins

PubMed Central

Attardi, Barbara J.; Zeleznik, Anthony; Simhan, Hyagriv; Chiao, Jye Ping; Mattison, Donald R; Caritis, Steve N

2007-01-01

Condensation 17-hydroxyprogesterone caproate is not better than progesterone in binding to progesterone or glucocorticoid receptors or eliciting gene expression in progesterone responsive genes. Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate (17-OHPC), and related progestins. Objective To determine whether the reduction in premature birth attributable to 17-OHPC occurs because of a greater affinity for progesterone (PR) or glucocorticoid (GR) receptors or by enhanced stimulation of progestogen responsive genes when compared with progesterone. Study Design We performed competitive steroid hormone receptor binding assays using cytosols expressing either recombinant human PR-A (rhPR-A) or B (rhPR-B) or rabbit uterine or thymic cytosols. We used four different carcinoma cell lines to assess transactivation of reporter genes or induction of alkaline phosphatase. Results Relative binding affinity of 17-OHPC for rhPR-B, rhPR-A and rabbit PR was 26–30% that of progesterone. Binding of progesterone to rabbit thymic GR was weak. 17-OHPC was comparable to progesterone in eliciting gene expression in all cell lines studied. Conclusions Binding to PR, GR or expression of progesterone-responsive genes is no greater with 17-OHPC than with progesterone. Other mechanisms must account for the beneficial effect of 17-OHPC on preterm birth rates. PMID:18060946

Frequency Modulation of Transcriptional Bursting Enables Sensitive and Rapid Gene Regulation.

PubMed

Li, Congxin; Cesbron, François; Oehler, Michael; Brunner, Michael; Höfer, Thomas

2018-04-25

Gene regulation is a complex non-equilibrium process. Here, we show that quantitating the temporal regulation of key gene states (transcriptionally inactive, active, and refractory) provides a parsimonious framework for analyzing gene regulation. Our theory makes two non-intuitive predictions. First, for transcription factors (TFs) that regulate transcription burst frequency, as opposed to amplitude or duration, weak TF binding is sufficient to elicit strong transcriptional responses. Second, refractoriness of a gene after a transcription burst enables rapid responses to stimuli. We validate both predictions experimentally by exploiting the natural, optogenetic-like responsiveness of the Neurospora GATA-type TF White Collar Complex (WCC) to blue light. Further, we demonstrate that differential regulation of WCC target genes is caused by different gene activation rates, not different TF occupancy, and that these rates are tuned by both the core promoter and the distance between TF-binding site and core promoter. In total, our work demonstrates the relevance of a kinetic, non-equilibrium framework for understanding transcriptional regulation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Marek's disease virus protein kinase gene identified within the short unique region of the viral genome is not essential for viral replication in cell culture and vaccine-induced immunity in chickens.

PubMed

Sakaguchi, M; Urakawa, T; Hirayama, Y; Miki, N; Yamamoto, M; Zhu, G S; Hirai, K

1993-07-01

The open reading frame (ORF) of 1206 bp within the short unique region (Us) of Marek's disease virus type 1 (MDV1) shows significant homology with the herpes simplex virus type 1 US3 gene encoding protein kinase (PK). The lacZ gene of Escherichia coli was inserted within the ORF, designated MDV1-US3, of MDV1 K544 strain DNA by homologous recombination. The plaque-purified recombinant MDV1 stably expressed the beta-galactosidase encoded by the inserted lacZ gene in infected cells and replicated well as the parental K544 strain. Antibodies against both MDV1 antigen and beta-galactosidase were detected in the sera of chickens immunized with recombinant MDV1. Chickens vaccinated with the recombinant MDV1 were protected from challenge with virulent MDV1. The MDV1 US3 gene expressed by a baculovirus vector encoded a 44-kDa protein. Mouse antisera against the 44-kDa protein reacted with two proteins of 44 and 45 kDa in extracts of cells infected with MDV1 but not with MDV types 2 or 3. The PK activity was detected in immune complexes of the anti-44-kDa sera with extracts of cells infected with MDV1 but not with the recombinant MDV1. Thus, PK encoded from the MDV1-US3 is not essential for virus replication in cell culture and vaccine-induced immunity.

Extending Hypothesis Testing of Edge Organizations Using Functional Magnetic Resonance Imaging (fMRI) During ELICIT

DTIC Science & Technology

2010-06-01

task difficulty and response correctness on neural systems supporting fluid reasoning. Cognitive Neurodynamics 1 (1): 71-84. Kaplan, J.T., Iacoboni...dynamic influences on decision-making and trust during social interaction. ELICITing Behavior ELICIT is designed to explore social and cognitive ...a person’s own self-awareness in the game experience, (2) their cognitive processes of reasoning, and (3) the modulation of uncertainty that primes

Monoethylhexyl Phthalate Elicits an Inflammatory Response in Adipocytes Characterized by Alterations in Lipid and Cytokine Pathways

PubMed Central

Manteiga, Sara; Lee, Kyongbum

2016-01-01

Background: A growing body of evidence links endocrine-disrupting chemicals (EDCs) with obesity-related metabolic diseases. While it has been shown that EDCs can predispose individuals toward adiposity by affecting developmental processes, little is known about the chemicals’ effects on adult adipose tissue. Objectives: Our aim was to study the effects of low, physiologically relevant doses of EDCs on differentiated murine adipocytes. Methods: We combined metabolomics, proteomics, and gene expression analysis to characterize the effects of mono-ethylhexyl phthalate (MEHP) in differentiated adipocytes. Results: Repeated exposure to MEHP over several days led to changes in metabolite and enzyme levels indicating elevated lipogenesis and lipid oxidation. The chemical exposure also increased expression of major inflammatory cytokines, including chemotactic factors. Proteomic and gene expression analysis revealed significant alterations in pathways regulated by peroxisome proliferator activated receptor-γ (PPARγ). Inhibiting the nuclear receptor’s activity using a chemical antagonist abrogated not only the alterations in PPARγ-regulated metabolic pathways, but also the increases in cytokine expression. Conclusions: Our results show that MEHP can induce a pro-inflammatory state in differentiated adipocytes. This effect is at least partially mediated PPARγ. Citation: Manteiga S, Lee K. 2017. Monoethylhexyl phthalate elicits an inflammatory response in adipocytes characterized by alterations in lipid and cytokine pathways. Environ Health Perspect 125:615–622; http://dx.doi.org/10.1289/EHP464 PMID:27384973

Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation

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

Zhou, Tongqing; Doria-Rose, Nicole A.; Cheng, Cheng

While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralizationmore » character). To a first approximation, the immunogenicity of the glycan-shielded protein surface was negligible, with Env-elicited neutralization (ID50) proportional to the exponential of the protein-surface area accessible to antibody. Based on these high titers and exponential relationship, we propose site-selective deglycosylated trimers as priming immunogens to increase the frequency of site-targeting antibodies.« less

Brain-heart linear and nonlinear dynamics during visual emotional elicitation in healthy subjects.

PubMed

Valenza, G; Greco, A; Gentili, C; Lanata, A; Toschi, N; Barbieri, R; Sebastiani, L; Menicucci, D; Gemignani, A; Scilingo, E P

2016-08-01

This study investigates brain-heart dynamics during visual emotional elicitation in healthy subjects through linear and nonlinear coupling measures of EEG spectrogram and instantaneous heart rate estimates. To this extent, affective pictures including different combinations of arousal and valence levels, gathered from the International Affective Picture System, were administered to twenty-two healthy subjects. Time-varying maps of cortical activation were obtained through EEG spectral analysis, whereas the associated instantaneous heartbeat dynamics was estimated using inhomogeneous point-process linear models. Brain-Heart linear and nonlinear coupling was estimated through the Maximal Information Coefficient (MIC), considering EEG time-varying spectra and point-process estimates defined in the time and frequency domains. As a proof of concept, we here show preliminary results considering EEG oscillations in the θ band (4-8 Hz). This band, indeed, is known in the literature to be involved in emotional processes. MIC highlighted significant arousal-dependent changes, mediated by the prefrontal cortex interplay especially occurring at intermediate arousing levels. Furthermore, lower and higher arousing elicitations were associated to not significant brain-heart coupling changes in response to pleasant/unpleasant elicitations.

Using photo-elicitation to understand reasons for repeated self-harm: a qualitative study.

PubMed

Edmondson, Amanda J; Brennan, Cathy; House, Allan O

2018-04-11

Reasons for self-harm are not well understood. One of the reasons for this is that first-hand accounts are usually elicited using traditional interview and questionnaire methods. This study aims to explore the acceptability of using an approach (photo-elicitation) that does not rely on solely verbal or written techniques, and to make a preliminary assessment of whether people can usefully employ images to support a discussion about the reasons why they self-harm. Interviews with eight participants using photo elicitation, a method in which photographs produced by the participant are used as a stimulus and guide within the interview. Participants responded positively to using images to support a discussion about their self-harm and readily incorporated images in the interview. Four main themes were identified representing negative and positive or adaptive purposes of self-harm: self-harm as a response to distress, self-harm to achieve mastery, self-harm as protective and self-harm as a language or form of communication. Employing this novel approach was useful in broadening our understanding of self-harm.

When gene medication is also genetic modification--regulating DNA treatment.

PubMed

Foss, Grethe S; Rogne, Sissel

2007-07-26

The molecular methods used in DNA vaccination and gene therapy resemble in many ways the methods applied in genetic modification of organisms. In some regulatory regimes, this creates an overlap between 'gene medication' and genetic modification. In Norway, an animal injected with plasmid DNA, in the form of DNA vaccine or gene therapy, currently is viewed as being genetically modified for as long as the added DNA is present in the animal. However, regulating a DNA-vaccinated animal as genetically modified creates both regulatory and practical challenges. It is also counter-intuitive to many biologists. Since immune responses can be elicited also to alter traits, the borderline between vaccination and the modification of properties is no longer distinct. In this paper, we discuss the background for the Norwegian interpretation and ways in which the regulatory challenge can be handled.

Studying Functions of All Yeast Genes Simultaneously

NASA Technical Reports Server (NTRS)

Stolc, Viktor; Eason, Robert G.; Poumand, Nader; Herman, Zelek S.; Davis, Ronald W.; Anthony Kevin; Jejelowo, Olufisayo

2006-01-01

A method of studying the functions of all the genes of a given species of microorganism simultaneously has been developed in experiments on Saccharomyces cerevisiae (commonly known as baker's or brewer's yeast). It is already known that many yeast genes perform functions similar to those of corresponding human genes; therefore, by facilitating understanding of yeast genes, the method may ultimately also contribute to the knowledge needed to treat some diseases in humans. Because of the complexity of the method and the highly specialized nature of the underlying knowledge, it is possible to give only a brief and sketchy summary here. The method involves the use of unique synthetic deoxyribonucleic acid (DNA) sequences that are denoted as DNA bar codes because of their utility as molecular labels. The method also involves the disruption of gene functions through deletion of genes. Saccharomyces cerevisiae is a particularly powerful experimental system in that multiple deletion strains easily can be pooled for parallel growth assays. Individual deletion strains recently have been created for 5,918 open reading frames, representing nearly all of the estimated 6,000 genetic loci of Saccharomyces cerevisiae. Tagging of each deletion strain with one or two unique 20-nucleotide sequences enables identification of genes affected by specific growth conditions, without prior knowledge of gene functions. Hybridization of bar-code DNA to oligonucleotide arrays can be used to measure the growth rate of each strain over several cell-division generations. The growth rate thus measured serves as an index of the fitness of the strain.

Drosophila melanogaster mounts a unique immune response to the Rhabdovirus sigma virus.

PubMed

Tsai, C W; McGraw, E A; Ammar, E-D; Dietzgen, R G; Hogenhout, S A

2008-05-01

Rhabdoviruses are important pathogens of humans, livestock, and plants that are often vectored by insects. Rhabdovirus particles have a characteristic bullet shape with a lipid envelope and surface-exposed transmembrane glycoproteins. Sigma virus (SIGMAV) is a member of the Rhabdoviridae and is a naturally occurring disease agent of Drosophila melanogaster. The infection is maintained in Drosophila populations through vertical transmission via germ cells. We report here the nature of the Drosophila innate immune response to SIGMAV infection as revealed by quantitative reverse transcription-PCR analysis of differentially expressed genes identified by microarray analysis. We have also compared and contrasted the immune response of the host with respect to two nonenveloped viruses, Drosophila C virus (DCV) and Drosophila X virus (DXV). We determined that SIGMAV infection upregulates expression of the peptidoglycan receptor protein genes PGRP-SB1 and PGRP-SD and the antimicrobial peptide (AMP) genes Diptericin-A, Attacin-A, Attacin-B, Cecropin-A1, and Drosocin. SIGMAV infection did not induce PGRP-SA and the AMP genes Drosomycin-B, Metchnikowin, and Defensin that are upregulated in DCV and/or DXV infections. Expression levels of the Toll and Imd signaling cascade genes are not significantly altered by SIGMAV infection. These results highlight shared and unique aspects of the Drosophila immune response to the three viruses and may shed light on the nature of the interaction with the host and the evolution of these associations.

Drosophila melanogaster Mounts a Unique Immune Response to the Rhabdovirus Sigma virus▿

PubMed Central

Tsai, C. W.; McGraw, E. A.; Ammar, E.-D.; Dietzgen, R. G.; Hogenhout, S. A.

2008-01-01

Rhabdoviruses are important pathogens of humans, livestock, and plants that are often vectored by insects. Rhabdovirus particles have a characteristic bullet shape with a lipid envelope and surface-exposed transmembrane glycoproteins. Sigma virus (SIGMAV) is a member of the Rhabdoviridae and is a naturally occurring disease agent of Drosophila melanogaster. The infection is maintained in Drosophila populations through vertical transmission via germ cells. We report here the nature of the Drosophila innate immune response to SIGMAV infection as revealed by quantitative reverse transcription-PCR analysis of differentially expressed genes identified by microarray analysis. We have also compared and contrasted the immune response of the host with respect to two nonenveloped viruses, Drosophila C virus (DCV) and Drosophila X virus (DXV). We determined that SIGMAV infection upregulates expression of the peptidoglycan receptor protein genes PGRP-SB1 and PGRP-SD and the antimicrobial peptide (AMP) genes Diptericin-A, Attacin-A, Attacin-B, Cecropin-A1, and Drosocin. SIGMAV infection did not induce PGRP-SA and the AMP genes Drosomycin-B, Metchnikowin, and Defensin that are upregulated in DCV and/or DXV infections. Expression levels of the Toll and Imd signaling cascade genes are not significantly altered by SIGMAV infection. These results highlight shared and unique aspects of the Drosophila immune response to the three viruses and may shed light on the nature of the interaction with the host and the evolution of these associations. PMID:18378641

Cloning of genes required for hypersensitivity and pathogenicity in Pseudomonas syringae pv. aptata.

PubMed

Minardi, P

1995-01-01

A genomic library of Pseudomonas syringae pv. aptata strain NCPPB 2664, which causes bacterial blight of sugar beet, lettuce and other plants, was constructed in the cosmid vector pCPP31. The 13.4 kb EcoRI fragment of the cosmid pHIR11, containing the hrp (hypersensitive response and pathogenicity) gene cluster of the closely related bacterium Pseudomonas syringae pv. syringae strain 61, was used as a probe to identify a homologous hrp gene cluster in P. syringae pv. aptata. Thirty of 2500 cosmid clones, screened by colony hybridization, gave a strong hybridization signal with the probe, but none of these conferred to the non-pathogenic bacterium, Pseudomonas fluorescens, the ability to elicit the hypersensitive response (HR) in tobacco. Southern blot analysis of EcoRI-digested genomic DNA of P. syringae pv. aptata showed hybridizing bands of 12 kb and 4.4 kb. Only a 12 kb fragment hybridized in digests of the cosmids. Cosmid clone pCPP1069 was mutagenized with Tn10-minitet and marker-exchanged into the genome of P. syringae pv. aptata. Three resulting prototrophic mutant strains failed to elicit the HR in tobacco and to cause disease in lettuce. The DNA flanking the Tn10-minitet insertions from mutated derivatives of pCPP1069 hybridized with the 10.6 kb Bg/II fragment of pHIR11. These results indicate that P. syringae pv. aptata harbours hrp genes that are similar to, but arranged differently from, homologous hrp genes of P. syringae pv. syringae.

Glutathione and fungal elicitor regulation of a plant defense gene promoter in electroporated protoplasts

PubMed Central

Dron, Michel; Clouse, Steven D.; Dixon, Richard A.; Lawton, Michael A.; Lamb, Christopher J.

1988-01-01

To investigate the mechanisms underlying activation of plant defenses against microbial attack we have studied elicitor regulation of a chimeric gene comprising the 5′ flanking region of a defense gene encoding the phytoalexin biosynthetic enzyme chalcone synthase fused to a bacterial chloramphenicol acetyltransferase gene. Glutathione or fungal elicitor caused a rapid, marked but transient expression of the chimeric gene electroporated into soybean protoplasts. The response closely resembled that of endogenous chalcone synthase genes in suspension cultured cells. Functional analysis of 5′ deletions suggests that promoter activity is determined by an elicitor-regulated activator located between the “TATA box” and nucleotide position -173 and an upstream silencer between -173 and -326. These cis-acting elements function in the transduction of the elicitation signal to initiate elaboration of an inducible defense response. Images PMID:16593981

The Caenorhabditis elegans rsd-2 and rsd-6 genes are required for chromosome functions during exposure to unfavorable environments.

PubMed

Han, Wang; Sundaram, Prema; Kenjale, Himanshu; Grantham, James; Timmons, Lisa

2008-04-01

In Caenorhabditis elegans, exogenous dsRNA can elicit systemic RNAi, a process that requires the function of many genes. Considering that the activities of many of these genes are also required for normal development, it is surprising that exposure to high concentrations of dsRNA does not elicit adverse consequences to animals. Here, we report inducible phenotypes in attenuated C. elegans strains reared in environments that include nonspecific dsRNA and elevated temperature. Under these conditions, chromosome integrity is compromised in RNAi-defective strains harboring mutations in rsd-2 or rsd-6. Specifically, rsd-2 mutants display defects in transposon silencing, while meiotic chromosome disjunction is affected in rsd-6 mutants. RSD-2 proteins localize to multiple cellular compartments, including the nucleolus and cytoplasmic compartments that, in part, are congruent with calreticulin and HAF-6. We considered that the RNAi defects in rsd-2 mutants might have relevance to membrane-associated functions; however, endomembrane compartmentalization and endocytosis/exocytosis markers in rsd-2 and rsd-6 mutants appear normal. The mutants also possess environmentally sensitive defects in cell-autonomous RNAi elicited from transgene-delivered dsRNAs. Thus, the ultimate functions of rsd-2 and rsd-6 in systemic RNAi are remarkably complex and environmentally responsive.

Eliciting consumer preferences for health plans.

PubMed

Booske, B C; Sainfort, F; Hundt, A S

1999-10-01

To examine (1) what people say is important to them in choosing a health plan; (2) the effect, if any, that giving health plan information has on what people say is important to them; and (3) the effect of preference elicitation methods on what people say is important. A random sample of 201 Wisconsin state employees who participated in a health plan choice experiment during the 1995 open enrollment period. We designed a computer system to guide subjects through the review of information about health plan options. The system began by eliciting the stated preferences of the subjects before they viewed the information, at time 0. Subjects were given an opportunity to revise their preference structures first after viewing summary information about four health plans (time 1) and then after viewing more extensive, detailed information about the same options (time 2). At time 2, these individuals were also asked to rate the relative importance of a predefined list of health plan features presented to them. Data were collected on the number of attributes listed at each point in time and the importance weightings assigned to each attribute. In addition, each item on the attribute list was content analyzed. The provision of information changes the preference structures of individuals. Costs (price) and coverage dominated the attributes cited both before and after looking at health plan information. When presented with information on costs, quality, and how plans work, many of these relatively well educated consumers revised their preference structures; yet coverage and costs remained the primary cited attributes. Although efforts to provide health plan information should continue, decisions on the information to provide and on making it available are not enough. Individuals need help in understanding, processing, and using the information to construct their preferences and make better decisions.

PREDICTION OF SOLAR FLARES USING UNIQUE SIGNATURES OF MAGNETIC FIELD IMAGES

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

Raboonik, Abbas; Safari, Hossein; Alipour, Nasibe

Prediction of solar flares is an important task in solar physics. The occurrence of solar flares is highly dependent on the structure and topology of solar magnetic fields. A new method for predicting large (M- and X-class) flares is presented, which uses machine learning methods applied to the Zernike moments (ZM) of magnetograms observed by the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory for a period of six years from 2010 June 2 to 2016 August 1. Magnetic field images consisting of the radial component of the magnetic field are converted to finite sets of ZMs andmore » fed to the support vector machine classifier. ZMs have the capability to elicit unique features from any 2D image, which may allow more accurate classification. The results indicate whether an arbitrary active region has the potential to produce at least one large flare. We show that the majority of large flares can be predicted within 48 hr before their occurrence, with only 10 false negatives out of 385 flaring active region magnetograms and 21 false positives out of 179 non-flaring active region magnetograms. Our method may provide a useful tool for the prediction of solar flares, which can be employed alongside other forecasting methods.« less

Powerful multilocus tests of genetic association in the presence of gene-gene and gene-environment interactions.

PubMed

Chatterjee, Nilanjan; Kalaylioglu, Zeynep; Moslehi, Roxana; Peters, Ulrike; Wacholder, Sholom

2006-12-01

In modern genetic epidemiology studies, the association between the disease and a genomic region, such as a candidate gene, is often investigated using multiple SNPs. We propose a multilocus test of genetic association that can account for genetic effects that might be modified by variants in other genes or by environmental factors. We consider use of the venerable and parsimonious Tukey's 1-degree-of-freedom model of interaction, which is natural when individual SNPs within a gene are associated with disease through a common biological mechanism; in contrast, many standard regression models are designed as if each SNP has unique functional significance. On the basis of Tukey's model, we propose a novel but computationally simple generalized test of association that can simultaneously capture both the main effects of the variants within a genomic region and their interactions with the variants in another region or with an environmental exposure. We compared performance of our method with that of two standard tests of association, one ignoring gene-gene/gene-environment interactions and the other based on a saturated model of interactions. We demonstrate major power advantages of our method both in analysis of data from a case-control study of the association between colorectal adenoma and DNA variants in the NAT2 genomic region, which are well known to be related to a common biological phenotype, and under different models of gene-gene interactions with use of simulated data.

Functional genomics reveals the induction of inflammatory response and metalloproteinase gene expression during lethal Ebola virus infection.

PubMed

Cilloniz, Cristian; Ebihara, Hideki; Ni, Chester; Neumann, Gabriele; Korth, Marcus J; Kelly, Sara M; Kawaoka, Yoshihiro; Feldmann, Heinz; Katze, Michael G

2011-09-01

Ebola virus is the etiologic agent of a lethal hemorrhagic fever in humans and nonhuman primates with mortality rates of up to 90%. Previous studies with Zaire Ebola virus (ZEBOV), mouse-adapted virus (MA-ZEBOV), and mutant viruses (ZEBOV-NP(ma), ZEBOV-VP24(ma), and ZEBOV-NP/VP24(ma)) allowed us to identify the mutations in viral protein 24 (VP24) and nucleoprotein (NP) responsible for acquisition of high virulence in mice. To elucidate specific molecular signatures associated with lethality, we compared global gene expression profiles in spleen samples from mice infected with these viruses and performed an extensive functional analysis. Our analysis showed that the lethal viruses (MA-ZEBOV and ZEBOV-NP/VP24(ma)) elicited a strong expression of genes 72 h after infection. In addition, we found that although the host transcriptional response to ZEBOV-VP24(ma) was nearly the same as that to ZEBOV-NP/VP24(ma), the contribution of a mutation in the NP gene was required for a lethal phenotype. Further analysis indicated that one of the most relevant biological functions differentially regulated by the lethal viruses was the inflammatory response, as was the induction of specific metalloproteinases, which were present in our newly identify functional network that was associated with Ebola virus lethality. Our results suggest that this dysregulated proinflammatory response increased the severity of disease. Consequently, the newly discovered molecular signature could be used as the starting point for the development of new drugs and therapeutics. To our knowledge, this is the first study that clearly defines unique molecular signatures associated with Ebola virus lethality.

The Frame Constraint on Experimentally Elicited Speech Errors in Japanese.

PubMed

Saito, Akie; Inoue, Tomoyoshi

2017-06-01

The so-called syllable position effect in speech errors has been interpreted as reflecting constraints posed by the frame structure of a given language, which is separately operating from linguistic content during speech production. The effect refers to the phenomenon that when a speech error occurs, replaced and replacing sounds tend to be in the same position within a syllable or word. Most of the evidence for the effect comes from analyses of naturally occurring speech errors in Indo-European languages, and there are few studies examining the effect in experimentally elicited speech errors and in other languages. This study examined whether experimentally elicited sound errors in Japanese exhibits the syllable position effect. In Japanese, the sub-syllabic unit known as "mora" is considered to be a basic sound unit in production. Results showed that the syllable position effect occurred in mora errors, suggesting that the frame constrains the ordering of sounds during speech production.

Counterconditioning reduces cue-induced craving and actual cue-elicited consumption.

PubMed

Van Gucht, Dinska; Baeyens, Frank; Vansteenwegen, Debora; Hermans, Dirk; Beckers, Tom

2010-10-01

Cue-induced craving is not easily reduced by an extinction or exposure procedure and may constitute an important route toward relapse in addictive behavior after treatment. In the present study, we investigated the effectiveness of counterconditioning as an alternative procedure to reduce cue-induced craving, in a nonclinical population. We found that a cue, initially paired with chocolate consumption, did not cease to elicit craving for chocolate after extinction (repeated presentation of the cue without chocolate consumption), but did so after counterconditioning (repeated pairing of the cue with consumption of a highly disliked liquid, Polysorbate 20). This effect persisted after 1 week. Counterconditioning moreover was more effective than extinction in disrupting reported expectancy to get to eat chocolate, and also appeared to be more effective in reducing actual cue-elicited chocolate consumption. These results suggest that counterconditioning may be more promising than cue exposure for the prevention of relapse in addictive behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Transduction of a Foreign Histocompatibility Gene into the Arterial Wall Induces Vasculitis

NASA Astrophysics Data System (ADS)

Nabel, Elizabeth G.; Plautz, Gregory; Nabel, Gary J.

1992-06-01

Autoimmune vasculitis represents a disease characterized by focal inflammation within arteries at multiple sites in the vasculature. Therapeutic interventions in this disease are empirical and often unsuccessful, and the mechanisms of immune injury are not well-defined. The direct transfer of recombinant genes and their expression in the arterial wall provides an opportunity to explore the pathogenesis and treatment of vascular disease. In this report, an animal model for vasculitis has been developed. Inflammation has been elicited by direct gene transfer of a foreign class I major histocompatibility complex gene, HLA-B7, to specific sites in porcine arteries. Transfer and expression of this recombinant gene was confirmed by a polymerase chain reaction and immunohistochemistry, and cytolytic T cells specific for HLA-B7 were detected. These findings demonstrate that expression of a recombinant gene in the vessel wall can induce a focal immune response and suggest that vessel damage induced by cell-mediated immune injury can initiate vasculitis.

Transcriptional Coupling of Neighboring Genes and Gene Expression Noise: Evidence that Gene Orientation and Noncoding Transcripts Are Modulators of Noise

PubMed Central

Wang, Guang-Zhong; Lercher, Martin J.; Hurst, Laurence D.

2011-01-01

Abstract How is noise in gene expression modulated? Do mechanisms of noise control impact genome organization? In yeast, the expression of one gene can affect that of a very close neighbor. As the effect is highly regionalized, we hypothesize that genes in different orientations will have differing degrees of coupled expression and, in turn, different noise levels. Divergently organized gene pairs, in particular those with bidirectional promoters, have close promoters, maximizing the likelihood that expression of one gene affects the neighbor. With more distant promoters, the same is less likely to hold for gene pairs in nondivergent orientation. Stochastic models suggest that coupled chromatin dynamics will typically result in low abundance-corrected noise (ACN). Transcription of noncoding RNA (ncRNA) from a bidirectional promoter, we thus hypothesize to be a noise-reduction, expression-priming, mechanism. The hypothesis correctly predicts that protein-coding genes with a bidirectional promoter, including those with a ncRNA partner, have lower ACN than other genes and divergent gene pairs uniquely have correlated ACN. Moreover, as predicted, ACN increases with the distance between promoters. The model also correctly predicts ncRNA transcripts to be often divergently transcribed from genes that a priori would be under selection for low noise (essential genes, protein complex genes) and that the latter genes should commonly reside in divergent orientation. Likewise, that genes with bidirectional promoters are rare subtelomerically, cluster together, and are enriched in essential gene clusters is expected and observed. We conclude that gene orientation and transcription of ncRNAs are candidate modulators of noise. PMID:21402863

Systemic Induction of the Small Antibacterial Compound in the Leaf Exudate During Benzothiadiazole-elicited Systemic Acquired Resistance in Pepper

PubMed Central

Lee, Boyoung; Park, Yong-Soon; Yi, Hwe-Su; Ryu, Choong-Min

2013-01-01

Plants protect themselves from diverse potential pathogens by induction of the immune systems such as systemic acquired resistance (SAR). Most bacterial plant pathogens thrive in the intercellular space (apoplast) of plant tissues and cause symptoms. The apoplastic leaf exudate (LE) is believed to contain nutrients to provide food resource for phytopathogenic bacteria to survive and to bring harmful phytocompounds to protect plants against bacterial pathogens. In this study, we employed the pepper-Xanthomonas axonopodis system to assess whether apoplastic fluid from LE in pepper affects the fitness of X. axonopodis during the induction of SAR. The LE was extracted from pepper leaves 7 days after soil drench-application of a chemical trigger, benzothiadiazole (BTH). Elicitation of plant immunity was confirmed by significant up-regulation of four genes, CaPR1, CaPR4, CaPR9, and CaCHI2, by BTH treatment. Bacterial fitness was evaluated by measuring growth rate during cultivation with LE from BTH- or water-treated leaves. LE from BTH-treatment significantly inhibited bacterial growth when compared to that from the water-treated control. The antibacterial activity of LE from BTH-treated samples was not affected by heating at 100°C for 30 min. Although the antibacterial molecules were not precisely identified, the data suggest that small (less than 5 kDa), heat-stable compound(s) that are present in BTH-induced LE directly attenuate bacterial growth during the elicitation of plant immunity. PMID:25288963

Concurrent Data Elicitation Procedures, Processes, and the Early Stages of L2 Learning: A Critical Overview

ERIC Educational Resources Information Center

Leow, Ronald P.; Grey, Sarah; Marijuan, Silvia; Moorman, Colleen

2014-01-01

Given the current methodological interest in eliciting direct data on the cognitive processes L2 learners employ as they interact with L2 data during the early stages of the learning process, this article takes a critical and comparative look at three concurrent data elicitation procedures currently employed in the SLA literature: Think aloud (TA)…

Immunization-elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability

PubMed Central

Zhao, Xuelian; Howell, Katie A.; He, Shihua; Brannan, Jennifer M.; Wec, Anna Z.; Davidson, Edgar; Turner, Hannah L.; Chiang, Chi-I; Lei, Lin; Fels, J. Maximilian; Vu, Hong; Shulenin, Sergey; Turonis, Ashley N.; Kuehne, Ana I.; Liu, Guodong; Ta, Mi; Wang, Yimeng; Sundling, Christopher; Xiao, Yongli; Spence, Jennifer S.; Doranz, Benjamin J.; Holtsberg, Frederick W.; Ward, Andrew B.; Chandran, Kartik; Dye, John M.; Qiu, Xiangguo; Li, Yuxing; Aman, M. Javad

2018-01-01

Summary While neutralizing antibodies are highly effective against ebolavirus infections, current experimental ebolavirus vaccines primarily elicit species-specific antibody responses. Here we describe an immunization-elicited macaque antibody (CA45) that clamps the internal fusion loop with the N-terminus of the ebolavirus glycoproteins (GP) and potently neutralizes Ebola, Sudan, Bundibugyo, and Reston viruses. CA45, alone or in combination with an antibody that blocks receptor binding, provided full protection against all pathogenic ebolaviruses in mice, guinea pigs, and ferrets. Analysis of memory B cells from the immunized macaque suggests that elicitation of broadly neutralizing antibodies (bNAbs) for ebolaviruses is possible but difficult, potentially due to the rarity of bNAb clones and their precursors. Unexpectedly, germline-reverted CA45, while exhibiting negligible binding to full-length GP, bound a proteolytically remodeled GP with picomolar affinity, suggesting that engineered ebolavirus vaccines could trigger rare bNAb precursors more robustly. These findings have important implications for developing pan-ebolavirus vaccine and immunotherapeutic cocktails. PMID:28525756

Eliciting Values of Patients with Multiple Chronic Conditions: Evaluation of a Patient-centered Framework

PubMed Central

Berry, Andrew B.L.; Lim, Catherine; Hartzler, Andrea L.; Hirsch, Tad; Ludman, Evette; Wagner, Edward H.; Ralston, James D.

2017-01-01

Patients with multiple chronic conditions often face competing demands for care, and they often do not agree with physicians on priorities for care. Patients ’ values shape their healthcare priorities, but existing methods for eliciting values do not necessarily meet patients ’ care planning needs. We developed a patient-centered values framework based on a field study with patients and caregivers. In this paper we report on a survey to evaluate how the framework generalizes beyond field study participants, and how well the framework supports values elicitation. We found that respondents frame values in a way that is consistent with the framework, and that domains of the framework can be used to elicit a breadth of potential values individuals with MCC express. These findings demonstrate how a patient-centered perspective on values can expand on the domains considered in values clarification methods andfacilitate patient-provider communication in establishing shared care priorities. PMID:29854107

Analysis of creative mathematical thinking ability by using model eliciting activities (MEAs)

NASA Astrophysics Data System (ADS)

Winda, A.; Sufyani, P.; Elah, N.

2018-05-01

Lack of creative mathematical thinking ability can lead to not accustomed with open ended problem. Students’ creative mathematical thinking ability in the first grade at one of junior high school in Tangerang City is not fully developed. The reason of students’ creative mathematical thinking ability is not optimally developed is so related with learning process which has done by the mathematics teacher, maybe the learning design that teacher use is unsuitable for increasing students’ activity in the learning process. This research objective is to see the differences in students’ ways of answering the problems in terms of students’ creative mathematical thinking ability during the implementation of Model Eliciting Activities (MEAs). This research use post-test experimental class design. The indicators for creative mathematical thinking ability in this research arranged in three parts, as follow: (1) Fluency to answer the problems; (2) Flexibility to solve the problems; (3) Originality of answers. The result of this research found that by using the same learning model and same instrument from Model Eliciting Activities (MEAs) there are some differences in the way students answer the problems and Model Eliciting Activities (MEAs) can be one of approach used to increase students’ creative mathematical thinking ability.

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface

PubMed Central

Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R.; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M.; Andrews, William; Saade, George R.; Ilekis, John V.; Reddy, Uma M.; Baldwin, Donald A.

2017-01-01

Background Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Methods Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment (n = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL (n = 8), PNL (n = 10), TL (n = 7) and TNL (n = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene’s 5′ promoter or 3′-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. Results The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of

Eliciting Production of L2 Target Structures through Priming Activities

ERIC Educational Resources Information Center

McDonough, Kim; Trofimovich, Pavel; Neumann, Heike

2015-01-01

This study focuses on the pedagogical applications of structural priming research in an English for academic purposes (EAP) context, investigating whether priming activities are an effective tool for eliciting production of target grammatical structures. University students across four EAP classes carried out a total of 6 information-exchange…

Preparing Beginning Teachers to Elicit and Interpret Students' Mathematical Thinking

ERIC Educational Resources Information Center

Sleep, Laurie; Boerst, Timothy A.

2012-01-01

This study investigated how teacher education assignments can be designed to support beginning teachers in learning to do the work of teaching. We examined beginners' formative assessment practices--in particular, their eliciting and interpreting of students' mathematical thinking--in the context of an elementary mathematics methods assignment,…

Chromosome 3p loss of heterozygosity is associated with a unique metabolic network in clear cell renal carcinoma

PubMed Central

Gatto, Francesco; Nookaew, Intawat; Nielsen, Jens

2014-01-01

Several common oncogenic pathways have been implicated in the emergence of renowned metabolic features in cancer, which in turn are deemed essential for cancer proliferation and survival. However, the extent to which different cancers coordinate their metabolism to meet these requirements is largely unexplored. Here we show that even in the heterogeneity of metabolic regulation a distinct signature encompassed most cancers. On the other hand, clear cell renal cell carcinoma (ccRCC) strongly deviated in terms of metabolic gene expression changes, showing widespread down-regulation. We observed a metabolic shift that associates differential regulation of enzymes in one-carbon metabolism with high tumor stage and poor clinical outcome. A significant yet limited set of metabolic genes that explained the partial divergence of ccRCC metabolism correlated with loss of von Hippel-Lindau tumor suppressor (VHL) and a potential activation of signal transducer and activator of transcription 1. Further network-dependent analyses revealed unique defects in nucleotide, one-carbon, and glycerophospholipid metabolism at the transcript and protein level, which contrasts findings in other tumors. Notably, this behavior is recapitulated by recurrent loss of heterozygosity in multiple metabolic genes adjacent to VHL. This study therefore shows how loss of heterozygosity, hallmarked by VHL deletion in ccRCC, may uniquely shape tumor metabolism. PMID:24550497

Children with autism respond differently to spontaneous, elicited and deferred imitation.

PubMed

Heimann, M; Nordqvist, E; Strid, K; Connant Almrot, J; Tjus, T

2016-05-01

Imitation, a key vehicle for both cognitive and social development, is often regarded as more difficult for children with autism spectrum disorders (ASD) than for children with Down syndrome (DS) or typically developing (TD) children. The current study investigates similarities and differences in observed elicited, spontaneous and deferred imitation using both actions with objects and gestures as imitation tasks in these groups. Imitation among 19 children with autism was compared with 20 children with DS and 23 TD children matched for mental and language age. Elicited imitation resulted in significantly lower scores for the ASD group compared with the other two groups, an effect mainly carried by a low level of gesture imitation among ASD children. We observed no differences among the groups for spontaneous imitation. However, children with ASD or DS displayed less deferred imitation than the TD group. Proneness to imitate also differed among groups: only 10 (53%) of the children with autism responded in the elicited imitation condition compared with all children with DS and almost all TD children (87%). These findings add to our understanding of the kind of imitation difficulties children with ASD might have. They also point to the necessity of not equating various imitation measures because these may capture different processes and be differently motivating for children with autism. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Ontology-based literature mining of E. coli vaccine-associated gene interaction networks.

PubMed

Hur, Junguk; Özgür, Arzucan; He, Yongqun

2017-03-14

Pathogenic Escherichia coli infections cause various diseases in humans and many animal species. However, with extensive E. coli vaccine research, we are still unable to fully protect ourselves against E. coli infections. To more rational development of effective and safe E. coli vaccine, it is important to better understand E. coli vaccine-associated gene interaction networks. In this study, we first extended the Vaccine Ontology (VO) to semantically represent various E. coli vaccines and genes used in the vaccine development. We also normalized E. coli gene names compiled from the annotations of various E. coli strains using a pan-genome-based annotation strategy. The Interaction Network Ontology (INO) includes a hierarchy of various interaction-related keywords useful for literature mining. Using VO, INO, and normalized E. coli gene names, we applied an ontology-based SciMiner literature mining strategy to mine all PubMed abstracts and retrieve E. coli vaccine-associated E. coli gene interactions. Four centrality metrics (i.e., degree, eigenvector, closeness, and betweenness) were calculated for identifying highly ranked genes and interaction types. Using vaccine-related PubMed abstracts, our study identified 11,350 sentences that contain 88 unique INO interactions types and 1,781 unique E. coli genes. Each sentence contained at least one interaction type and two unique E. coli genes. An E. coli gene interaction network of genes and INO interaction types was created. From this big network, a sub-network consisting of 5 E. coli vaccine genes, including carA, carB, fimH, fepA, and vat, and 62 other E. coli genes, and 25 INO interaction types was identified. While many interaction types represent direct interactions between two indicated genes, our study has also shown that many of these retrieved interaction types are indirect in that the two genes participated in the specified interaction process in a required but indirect process. Our centrality analysis of

Severity of dependence modulates smokers' neuronal cue reactivity and cigarette craving elicited by tobacco advertisement.

PubMed

Vollstädt-Klein, Sabine; Kobiella, Andrea; Bühler, Mira; Graf, Caroline; Fehr, Christoph; Mann, Karl; Smolka, Michael N

2011-01-01

Smoking-related cues elicit craving and mesocorticolimbic brain activation in smokers. Severity of nicotine dependence seems to moderate cue reactivity, but the direction and mechanisms of its influence remains unclear. Although tobacco control policies demand a ban on tobacco advertising, cue reactivity studies in smokers so far have not employed tobacco advertisement as experimental stimuli. We investigated whether tobacco advertisement elicits cue reactivity at a behavioral (subjective craving) and a neural level (using functional magnetic resonance imaging) in 22 smokers and 21 never-smokers. Moreover, we studied the influence of severity of dependence on cue reactivity. In smokers, tobacco advertisement elicited substantially more craving than control advertisement whereas never-smokers reported no cue induced craving. Surprisingly, neuronal cue reactivity did not differ between smokers and never-smokers. Moderately dependent smokers' craving increased over the course of the experiment, whereas highly dependent smokers' craving was unaffected. Moderately dependent smokers' brain activity elicited by tobacco advertisement was higher in the amygdala, hippocampus, putamen and thalamus compared with highly dependent smokers. Furthermore, limbic brain activation predicted picture recognition rates after the scanning session, even in never-smokers. Our findings show that tobacco advertisement elicits cigarette craving and neuronal cue reactivity primarily in moderately dependent smokers, indicating that they might be particularly responsive towards external smoking-related cues. On the other hand, neuronal cue reactivity and cigarette craving in highly dependent smokers is more likely triggered by internal cues such as withdrawal symptoms. Tobacco advertisement seems to likewise appeal to smokers and non-smokers, clarifying the potential danger especially for young non-smokers. © 2010 The Authors, Addiction Biology © 2010 Society for the Study of Addiction.

Uncertainty in geological linework: communicating the expert's tacit model to the data user(s) by expert elicitation.

NASA Astrophysics Data System (ADS)

Lawley, Russell; Barron, Mark; Lark, Murray

2015-04-01

At BGS, expert elicitation has been used to evaluate uncertainty of surveyed boundaries in several, common, geological scenarios. As a result, a 'collective' understanding of the issues surrounding each scenario has emerged. The work has provoked wider debate in three key areas: a) what can we do to resolve those scenarios where a 'consensus' of understanding cannot be achieved b) what does it mean for survey practices and subsequent use of maps in 3D models c) how do we communicate the 'collective' understanding of geological mapping (with or without consensus for specific scenarios). Previous work elicited expert judgement for uncertainty in six contrasting mapping scenarios. In five cases it was possible to arrive at a consensus model; in a sixth case experts with different experience (length of service, academic background) took very different views of the nature of the mapping problem. The scenario concerned identification of the boundary between two contrasting tills (one derived from Triassic source materials being red in colour; the other, derived from Jurassic materials being grey in colour). Initial debate during the elicitation identified that the colour contrast should provide some degree of confidence in locating the boundary via traditional auger-traverse survey methods. However, as the elicitation progressed, it became clear that the complexities of the relationship between the two Tills were not uniformly understood across the experts and the panel could not agree a consensus regarding the spatial uncertainty of the boundary. The elicitation process allowed a significant degree of structured knowledge-exchange between experts of differing backgrounds and was successful in identifying a measure of uncertainty for what was considered a contentious scenario. However, the findings have significant implications for a boundary-scenario that is widely mapped across the central regions of Great Britain. We will discuss our experience of the use of

Language Sample Analysis and Elicitation Technique Effects in Bilingual Children With and Without Language Impairment.

PubMed

Kapantzoglou, Maria; Fergadiotis, Gerasimos; Restrepo, M Adelaida

2017-10-17

This study examined whether the language sample elicitation technique (i.e., storytelling and story-retelling tasks with pictorial support) affects lexical diversity (D), grammaticality (grammatical errors per communication unit [GE/CU]), sentence length (mean length of utterance in words [MLUw]), and sentence complexity (subordination index [SI]), which are commonly used indices for diagnosing primary language impairment in Spanish-English-speaking children in the United States. Twenty bilingual Spanish-English-speaking children with typical language development and 20 with primary language impairment participated in the study. Four analyses of variance were conducted to evaluate the effect of language elicitation technique and group on D, GE/CU, MLUw, and SI. Also, 2 discriminant analyses were conducted to assess which indices were more effective for story retelling and storytelling and their classification accuracy across elicitation techniques. D, MLUw, and SI were influenced by the type of elicitation technique, but GE/CU was not. The classification accuracy of language sample analysis was greater in story retelling than in storytelling, with GE/CU and D being useful indicators of language abilities in story retelling and GE/CU and SI in storytelling. Two indices in language sample analysis may be sufficient for diagnosis in 4- to 5-year-old bilingual Spanish-English-speaking children.

Xylan utilization in human gut commensal bacteria is orchestrated by unique modular organization of polysaccharide-degrading enzymes.

PubMed

Zhang, Meiling; Chekan, Jonathan R; Dodd, Dylan; Hong, Pei-Ying; Radlinski, Lauren; Revindran, Vanessa; Nair, Satish K; Mackie, Roderick I; Cann, Isaac

2014-09-02

Enzymes that degrade dietary and host-derived glycans represent the most abundant functional activities encoded by genes unique to the human gut microbiome. However, the biochemical activities of a vast majority of the glycan-degrading enzymes are poorly understood. Here, we use transcriptome sequencing to understand the diversity of genes expressed by the human gut bacteria Bacteroides intestinalis and Bacteroides ovatus grown in monoculture with the abundant dietary polysaccharide xylan. The most highly induced carbohydrate active genes encode a unique glycoside hydrolase (GH) family 10 endoxylanase (BiXyn10A or BACINT_04215 and BACOVA_04390) that is highly conserved in the Bacteroidetes xylan utilization system. The BiXyn10A modular architecture consists of a GH10 catalytic module disrupted by a 250 amino acid sequence of unknown function. Biochemical analysis of BiXyn10A demonstrated that such insertion sequences encode a new family of carbohydrate-binding modules (CBMs) that binds to xylose-configured oligosaccharide/polysaccharide ligands, the substrate of the BiXyn10A enzymatic activity. The crystal structures of CBM1 from BiXyn10A (1.8 Å), a cocomplex of BiXyn10A CBM1 with xylohexaose (1.14 Å), and the CBM from its homolog in the Prevotella bryantii B14 Xyn10C (1.68 Å) reveal an unanticipated mode for ligand binding. A minimal enzyme mix, composed of the gene products of four of the most highly up-regulated genes during growth on wheat arabinoxylan, depolymerizes the polysaccharide into its component sugars. The combined biochemical and biophysical studies presented here provide a framework for understanding fiber metabolism by an important group within the commensal bacterial population known to influence human health.

Chromosomal localization of actin genes in the malaria mosquito Anopheles darlingi

PubMed Central

BRIDI, L. C.; SHARAKHOVA, M. V.; SHARAKHOV, I. V.; CORDEIRO, J.; AZEVEDO, G. M.; TADEI, W. P.; RAFAEL, M. S.

2012-01-01

Physical and genetic maps have been used for chromosomal localization of genes in vectors of infectious diseases. The availability of polytene chromosomes in malaria mosquitoes provides a unique opportunity to precisely map genes of interest. We report physical mapping of two actin genes on polytene chromosomes of the major malaria vector in Amazon Anopheles darlingi. The clones with the actin genes sequences were obtained from a cDNA library constructed from RNA isolated from adult females and males of An. darlingi. Each of the two clones was mapped to a unique site on the chromosomal arm 2L in subdivisions 21A (clone pl05-A04) and 23B (clone pl17-G06). The obtained results together with previous mapping data provide a suitable basis for comparative genomics and for establishing chromosomal homologies among major malaria vectors. PMID:22804344

Unique Temporal Expression of Triplicated Long-Wavelength Opsins in Developing Butterfly Eyes

PubMed Central

Arikawa, Kentaro; Iwanaga, Tomoyuki; Wakakuwa, Motohiro; Kinoshita, Michiyo

2017-01-01

Following gene duplication events, the expression patterns of the resulting gene copies can often diverge both spatially and temporally. Here we report on gene duplicates that are expressed in distinct but overlapping patterns, and which exhibit temporally divergent expression. Butterflies have sophisticated color vision and spectrally complex eyes, typically with three types of heterogeneous ommatidia. The eyes of the butterfly Papilio xuthus express two green- and one red-absorbing visual pigment, which came about via gene duplication events, in addition to one ultraviolet (UV)- and one blue-absorbing visual pigment. We localized mRNAs encoding opsins of these visual pigments in developing eye disks throughout the pupal stage. The mRNAs of the UV and blue opsin are expressed early in pupal development (pd), specifying the type of the ommatidium in which they appear. Red sensitive photoreceptors first express a green opsin mRNA, which is replaced later by the red opsin mRNA. Broadband photoreceptors (that coexpress the green and red opsins) first express the green opsin mRNA, later change to red opsin mRNA and finally re-express the green opsin mRNA in addition to the red mRNA. Such a unique temporal and spatial expression pattern of opsin mRNAs may reflect the evolution of visual pigments and provide clues toward understanding how the spectrally complex eyes of butterflies evolved. PMID:29238294

Cognitive constraints on constituent order: Evidence from elicited pantomime

PubMed Central

Hall, Matthew L.; Mayberry, Rachel I.; Ferreira, Victor S.

2014-01-01

To what extent does human cognition influence the structure of human language? Recent experiments using elicited pantomime suggest that the prevalence of Subject-Object-Verb (SOV) order across the world's languages may arise in part because SOV order is most compatible with how we conceptually represent transitive events (Goldin-Meadow, So, Özyürek, & Mylander, 2008). However, this raises the question as to why non-SOV orders exist. Two recent studies (Meir, Lifshitz, Ilkbasaran, & Padden, 2010; Gibson et al., 2013) suggest that SOV might be suboptimal for describing events in which both the agent and patient are plausible agents (e.g. a woman pushing a boy); we call these “reversible” events. We replicate these findings using elicited pantomime and offer a new interpretation. Meir et al.'s (2010) account is framed largely in terms of constraints on comprehension, while Gibson et al.'s (2013) account involves minimizing the risk of information loss or memory degradation. We offer an alternative hypothesis that is grounded in constraints on production. We consider the implications of these findings for the distribution of constituent order in the world's spoken languages and for the structure of emerging sign languages. PMID:23792806

Elicitation and treatment with precursors of phenolics synthesis improve low-molecular antioxidants and antioxidant capacity of buckwheat sprouts.

PubMed

Świeca, Michał

2016-01-01

Recently, an increase of interest in the modification of food products on each step of production (breeding, production technology, storage condition) is observed. Nutritional properties as well as level and activity of bioactive compounds in plant-origin food may be modified using a range of technological and biotechnological practices and elicitation should be mentioned between them. Elicitation with willow bark infusion supported by feeding with the phenylpropanoid pathway precursors were used for improving the quality of buckwheat sprouts. Special emphasis has been placed on the metabolomic and biochemical changes and the mechanism of overproduction of low-molecular antioxidants. The accumulation of phenolics is caused by stimulation of two main enzymes the phenylpropanoid pathway (tyrosine ammonia-lyase and phenylalanine ammonia-lyase). Tyrosine ammonia-lyase activities were effectively induced by feeding with tyrosine (about four times that of the control), whereas phenylalanine ammonia-lyase activity was the highest in the elicited control sprouts and those fed with shikimic acid (an increase by 60% compared to the control). Shikimic acid feeding (both elicited and non-elicited sprouts) effectively improved the total phenolics (by about 10% and 20%, respectively), condensed tannins (by about 30% and 28%, respectively), and flavonoids (by about 46% and 70%, respectively). Significant increase of vitexin, rutin, chlorogenic acid and isoorientin contents was also observed. The treatments increased the ascorbic acid content, too. Total antioxidant capacity of sprouts was most effectively increased by feeding with shikimic acid and further elicitation. The studies transfer biotechnology commonly used for the induction of overproduction of secondary metabolites in plant cell line systems to low-processed food production. The obtained results could be used for better understanding of the effect of elicitation and precursor feeding on antioxidants production and

Deletion of Specific Immune-Modulatory Genes from Modified Vaccinia Virus Ankara-Based HIV Vaccines Engenders Improved Immunogenicity in Rhesus Macaques

PubMed Central

O'Mara, Leigh A.; Gangadhara, Sailaja; McQuoid, Monica; Zhang, Xiugen; Zheng, Rui; Gill, Kiran; Verma, Meena; Yu, Tianwei; Johnson, Brent; Li, Bing; Derdeyn, Cynthia A.; Ibegbu, Chris; Altman, John D.; Hunter, Eric; Feinberg, Mark B.

2012-01-01

Modified vaccinia virus Ankara (MVA) is a safe, attenuated orthopoxvirus that is being developed as a vaccine vector but has demonstrated limited immunogenicity in several early-phase clinical trials. Our objective was to rationally improve the immunogenicity of MVA-based HIV/AIDS vaccines via the targeted deletion of specific poxvirus immune-modulatory genes. Vaccines expressing codon-optimized HIV subtype C consensus Env and Gag antigens were generated from MVA vector backbones that (i) harbor simultaneous deletions of four viral immune-modulatory genes, encoding an interleukin-18 (IL-18) binding protein, an IL-1β receptor, a dominant negative Toll/IL-1 signaling adapter, and CC-chemokine binding protein (MVAΔ4-HIV); (ii) harbor a deletion of an additional (fifth) viral gene, encoding uracil-DNA glycosylase (MVAΔ5-HIV); or (iii) represent the parental MVA backbone as a control (MVA-HIV). We performed head-to-head comparisons of the cellular and humoral immune responses that were elicited by these vectors during homologous prime-boost immunization regimens utilizing either high-dose (2 × 108 PFU) or low-dose (1 × 107 PFU) intramuscular immunization of rhesus macaques. At all time points, a majority of the HIV-specific T cell responses, elicited by all vectors, were directed against Env, rather than Gag, determinants, as previously observed with other vector systems. Both modified vectors elicited up to 6-fold-higher frequencies of HIV-specific CD8 and CD4 T cell responses and up to 25-fold-higher titers of Env (gp120)-specific binding (nonneutralizing) antibody responses that were relatively transient in nature. While the correlates of protection against HIV infection remain incompletely defined, our results indicate that the rational deletion of specific genes from MVA vectors can positively alter their cellular and humoral immunogenicity profiles in nonhuman primates. PMID:22973033

Serial analysis of gene expression (SAGE) in normal human trabecular meshwork.

PubMed

Liu, Yutao; Munro, Drew; Layfield, David; Dellinger, Andrew; Walter, Jeffrey; Peterson, Katherine; Rickman, Catherine Bowes; Allingham, R Rand; Hauser, Michael A

2011-04-08

To identify the genes expressed in normal human trabecular meshwork tissue, a tissue critical to the pathogenesis of glaucoma. Total RNA was extracted from human trabecular meshwork (HTM) harvested from 3 different donors. Extracted RNA was used to synthesize individual SAGE (serial analysis of gene expression) libraries using the I-SAGE Long kit from Invitrogen. Libraries were analyzed using SAGE 2000 software to extract the 17 base pair sequence tags. The extracted sequence tags were mapped to the genome using SAGE Genie map. A total of 298,834 SAGE tags were identified from all HTM libraries (96,842, 88,126, and 113,866 tags, respectively). Collectively, there were 107,325 unique tags. There were 10,329 unique tags with a minimum of 2 counts from a single library. These tags were mapped to known unique Unigene clusters. Approximately 29% of the tags (orphan tags) did not map to a known Unigene cluster. Thirteen percent of the tags mapped to at least 2 Unigene clusters. Sequence tags from many glaucoma-related genes, including myocilin, optineurin, and WD repeat domain 36, were identified. This is the first time SAGE analysis has been used to characterize the gene expression profile in normal HTM. SAGE analysis provides an unbiased sampling of gene expression of the target tissue. These data will provide new and valuable information to improve understanding of the biology of human aqueous outflow.

Separable Processes Before, During, and After the N400 Elicited by Previously Inferred and New Information: Evidence from Time-Frequency Decompositions

PubMed Central

Steele, Vaughn R.; Bernat, Edward M.; van den Broek, Paul; Collins, Paul F.; Patrick, Christopher J.; Marsolek, Chad J.

2012-01-01

Successful comprehension during reading often requires inferring information not explicitly presented. This information is readily accessible when subsequently encountered, and a neural correlate of this is an attenuation of the N400 event-related potential (ERP). We used ERPs and time-frequency (TF) analysis to investigate neural correlates of processing inferred information after a causal coherence inference had been generated during text comprehension. Participants read short texts, some of which promoted inference generation. After each text, they performed lexical decisions to target words that were unrelated or inference-related to the preceding text. Consistent with previous findings, inference-related words elicited an attenuated N400 relative to unrelated words. TF analyses revealed unique contributions to the N400 from activity occurring at 1–6 Hz (theta) and 0–2 Hz (delta), supporting the view that multiple, sequential processes underlie the N400. PMID:23165117

Separable processes before, during, and after the N400 elicited by previously inferred and new information: evidence from time-frequency decompositions.

PubMed

Steele, Vaughn R; Bernat, Edward M; van den Broek, Paul; Collins, Paul F; Patrick, Christopher J; Marsolek, Chad J

2013-01-25

Successful comprehension during reading often requires inferring information not explicitly presented. This information is readily accessible when subsequently encountered, and a neural correlate of this is an attenuation of the N400 event-related potential (ERP). We used ERPs and time-frequency (TF) analysis to investigate neural correlates of processing inferred information after a causal coherence inference had been generated during text comprehension. Participants read short texts, some of which promoted inference generation. After each text, they performed lexical decisions to target words that were unrelated or inference-related to the preceding text. Consistent with previous findings, inference-related words elicited an attenuated N400 relative to unrelated words. TF analyses revealed unique contributions to the N400 from activity occurring at 1-6 Hz (theta) and 0-2 Hz (delta), supporting the view that multiple, sequential processes underlie the N400. Copyright © 2012 Elsevier B.V. All rights reserved.

Exposure of mice to secondhand smoke elicits both transient and long-lasting transcriptional changes in cancer-related functional networks.

PubMed

Tommasi, Stella; Zheng, Albert; Besaratinia, Ahmad

2015-05-15

Secondhand smoke (SHS) has long been linked to lung cancer and other diseases in nonsmokers. Yet, the underlying mechanisms of SHS carcinogenicity in nonsmokers remain to be elucidated. We investigated the immediate and long-lasting effects of SHS exposure on gene expression in mice in vivo. We exposed mice whole body to SHS for 5 h/day, 5 days/week for 4 months in exposure chambers of a microprocessor-controlled smoking machine. Subsequently, we performed microarray gene expression profiling, genome-wide, to construct the pulmonary transcriptome of SHS-exposed mice, immediately after discontinuation of exposure (T0) and following 1-month (T1) and 7-month (T2) recoveries in clean air. Sub-chronic exposure of mice to SHS elicited a robust transcriptomic response, including both reversible and irreversible changes in gene expression. There were 674 differentially expressed transcripts immediately after treatment (T0), of which the majority were involved in xenobiotic metabolism, signaling, and innate immune response. Reduced, yet, substantial numbers of differentially expressed transcripts were detectable in mice after cessation of SHS-exposure (254 transcripts at T1 and 30 transcripts at T2). Top biofunctional networks disrupted in SHS-exposed mice, even after termination of exposure, were implicated in cancer, respiratory disease, and inflammatory disease. Our data show that exposure of mice to SHS induces both transient and long-lasting changes in gene expression, which impact cancer-related functional networks. The pattern of transcriptional changes in SHS-exposed mice may provide clues on the underlying mechanisms of lung tumorigenesis in nonsmokers. Our findings underscore the importance of eliminating SHS from environments where nonsmokers are unavoidably exposed to this carcinogen. © 2014 UICC.

Ventilatory Responses to Exercise While Eliciting the Relaxation Response,

DTIC Science & Technology

1982-04-16

Kent B. Pandolf, Bruce Cadarette, Leslie Levine, Ralph F. Goldman, and Herbert Benson. From the Division of Behavioral Medicine, Department of...been observed with the elicitation of the relaxation response at rest differ from those that occur during sleep or hypnosis (14). The relaxation response...alterations which were observed in our experimental group during the intervention period were not similar to those found with combined hypnosis and

Infection-derived lipids elicit a novel immune deficiency circuitry in arthropods