Impatience versus achievement strivings in the Type A pattern: Differential effects on students' health and academic achievement

NASA Technical Reports Server (NTRS)

Spence, Janet T.; Helmreich, Robert L.; Pred, Robert S.

1987-01-01

Psychometric analyses of college students' responses to the Jenkins Activity Survey, a self-report measure of the Type A behavior pattern, revealed the presence of two relatively independent factors. Based on these analyses, two scales, labeled Achievement Strivings (AS) and Impatience and Irritability (II), were developed. In two samples of male and female college students, scores on AS but not on II were found to be significantly correlated with grade point average. Responses to a health survey, on the other hand, indicated that frequency of physical complaints was significantly correlated with II but not with AS. These results suggest that there are two relatively independent factors in the Type A pattern that have differential effects on performance and health. Future research on the personality factors related to coronary heart disease and other disorders might more profitably focus on the syndrome reflected in the II scale than on the Type A pattern.

Differential immune gene expression profiles in susceptible and resistant full-sibling families of Atlantic salmon (Salmo salar) challenged with infectious pancreatic necrosis virus (IPNV).

PubMed

Reyes-López, Felipe E; Romeo, Jose S; Vallejos-Vidal, Eva; Reyes-Cerpa, Sebastián; Sandino, Ana M; Tort, Lluis; Mackenzie, Simon; Imarai, Mónica

2015-11-01

This study aims to identify at the expression level the immune-related genes associated with IPN-susceptible and resistant phenotypes in Atlantic salmon full-sibling families. We have analyzed thirty full-sibling families infected by immersion with IPNV and then classified as resistant or susceptible using a multivariate survival analysis based on a gamma-Cox frailty model and the Kaplan-Meier mortality curves. In four families within each group head kidneys were pooled for real-time PCR and one-color salmon-specific oligonucleotide microarray (21K) analysis at day 1 and 5 post-infection. Transcripts involved in innate response (IL-6, IFN-α), antigen presentation (HSP-70, HSP-90, MHC-I), TH1 response (IL-12, IFN-γ, CRFB6), immunosuppression (IL-10, TGF-β1) and leukocyte activation and migration (CCL-19, CD18) showed a differential expression pattern between both phenotypes, except in IL-6. In susceptible families, except for IFN-γ, the expressions dropped to basal values at day 5 post-infection. In resistant families, unlike susceptible families, levels remained high or increased (except for IL-6) at day 5. Transcriptomic analysis showed that both families have a clear differential expression pattern, resulting in a marked down-regulation in immune related genes involved in innate response, complement system, antigen recognition and activation of immune response in IPN-resistant. Down-regulation of genes, mainly related to tissue differentiation and protein degradation metabolism, was also observed in resistant families. We have identified an immune-related gene patterns associated with susceptibility and resistance to IPNV infection of Atlantic salmon. This suggests that a limited immune response is associated with resistant fish phenotype to IPNV challenge while a highly inflammatory but short response is associated with susceptibility. Copyright © 2015 Elsevier Ltd. All rights reserved.

Successful pod infections by Moniliophthora roreri result in differential Theobroma cacao gene expression depending on the clone's level of tolerance.

PubMed

Ali, Shahin S; Melnick, Rachel L; Crozier, Jayne; Phillips-Mora, Wilberth; Strem, Mary D; Shao, Jonathan; Zhang, Dapeng; Sicher, Richard; Meinhardt, Lyndel; Bailey, Bryan A

2014-09-01

An understanding of the tolerance mechanisms of Theobroma cacao used against Moniliophthora roreri, the causal agent of frosty pod rot, is important for the generation of stable disease-tolerant clones. A comparative view was obtained of transcript populations of infected pods from two susceptible and two tolerant clones using RNA sequence (RNA-Seq) analysis. A total of 3009 transcripts showed differential expression among clones. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis of differentially expressed genes indicated shifts in 152 different metabolic pathways between the tolerant and susceptible clones. Real-time quantitative reverse transcription polymerase chain reaction (real-time qRT-PCR) analyses of 36 genes verified the differential expression. Regression analysis validated a uniform progression in gene expression in association with infection levels and fungal loads in the susceptible clones. Expression patterns observed in the susceptible clones diverged in tolerant clones, with many genes showing higher expression at a low level of infection and fungal load. Principal coordinate analyses of real-time qRT-PCR data separated the gene expression patterns between susceptible and tolerant clones for pods showing malformation. Although some genes were constitutively differentially expressed between clones, most results suggested that defence responses were induced at low fungal load in the tolerant clones. Several elicitor-responsive genes were highly expressed in tolerant clones, suggesting rapid recognition of the pathogen and induction of defence genes. Expression patterns suggested that the jasmonic acid-ethylene- and/or salicylic acid-mediated defence pathways were activated in the tolerant clones, being enhanced by reduced brassinosteroid (BR) biosynthesis and catabolic inactivation of both BR and abscisic acids. Finally, several genes associated with hypersensitive response-like cell death were also induced in tolerant clones. © 2014 BSPP AND JOHN WILEY & SONS LTD.

Differential diagnosis between obsessive compulsive disorder and restrictive and repetitive behavioural patterns, activities and interests in autism spectrum disorders.

PubMed

Paula-Pérez, Isabel

2013-01-01

The obsessive compulsive disorder (OCD) and the restricted and repetitive patterns of behavior, interests and activities inherent to autism spectrum disorders (ASD) share a number of features that can make the differential diagnosis between them extremely difficult and lead to erroneous overdiagnosis of OCD in people with autism. In both cases there may appear to have a fixation on routine, ritualized patterns of verbal and nonverbal behavior, resistance to change, and highly restrictive interests, which becomes a real challenge for differentiating rituals, stereotypes and adherence to routines in ASD from obsessions and compulsions in OCD. This article provides key points to clarify this differential diagnosis through the analysis of emotional valence, content, function and psychological theories that explain the obsessions and compulsions in OCD, and the desire for sameness, stereotyped movements and limited interest in autism. The terms "obsession" and "compulsion" should no longer be used when referring to patterns of behavior, interests or restricted and repetitive activities in autism due to syntonic characteristics, low perception of personal responsibility and low neutralizing efforts. Treatment focuses on changing the environment, the use of socio-communicative compensatory strategies and behavioral modification techniques to improve cognitive and behavioral flexibility. When there is comorbidity between, exposure behavioral and response prevention techniques are then used, followed by others of more cognitive orientation if necessary. Copyright © 2012 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

Complex and extensive post-transcriptional regulation revealed by integrative proteomic and transcriptomic analysis of metabolite stress response in Clostridium acetobutylicum.

PubMed

Venkataramanan, Keerthi P; Min, Lie; Hou, Shuyu; Jones, Shawn W; Ralston, Matthew T; Lee, Kelvin H; Papoutsakis, E Terry

2015-01-01

Clostridium acetobutylicum is a model organism for both clostridial biology and solvent production. The organism is exposed to its own toxic metabolites butyrate and butanol, which trigger an adaptive stress response. Integrative analysis of proteomic and RNAseq data may provide novel insights into post-transcriptional regulation. The identified iTRAQ-based quantitative stress proteome is made up of 616 proteins with a 15 % genome coverage. The differentially expressed proteome correlated poorly with the corresponding differential RNAseq transcriptome. Up to 31 % of the differentially expressed proteins under stress displayed patterns opposite to those of the transcriptome, thus suggesting significant post-transcriptional regulation. The differential proteome of the translation machinery suggests that cells employ a different subset of ribosomal proteins under stress. Several highly upregulated proteins but with low mRNA levels possessed mRNAs with long 5'UTRs and strong RBS scores, thus supporting the argument that regulatory elements on the long 5'UTRs control their translation. For example, the oxidative stress response rubrerythrin was upregulated only at the protein level up to 40-fold without significant mRNA changes. We also identified many leaderless transcripts, several displaying different transcriptional start sites, thus suggesting mRNA-trimming mechanisms under stress. Downregulation of Rho and partner proteins pointed to changes in transcriptional elongation and termination under stress. The integrative proteomic-transcriptomic analysis demonstrated complex expression patterns of a large fraction of the proteome. Such patterns could not have been detected with one or the other omic analyses. Our analysis proposes the involvement of specific molecular mechanisms of post-transcriptional regulation to explain the observed complex stress response.

CpG methylation patterns and decitabine treatment response in acute myeloid leukemia cells and normal hematopoietic precursors

PubMed Central

Negrotto, Soledad; Ng, Kwok Peng; Jankowska, Ania M.; Bodo, Juraj; Gopalan, Banu; Guinta, Kathryn; Mulloy, James C.; Hsi, Eric; Maciejewski, Jaroslaw; Saunthararajah, Yogen

2011-01-01

The DNA hypomethylating drug decitabine maintains normal hematopoietic stem cell (HSC) self-renewal but induces terminal differentiation in acute myeloid leukemia (AML) cells. The basis for these contrasting cell-fates, and for selective CpG hypomethylation by decitabine, is poorly understood. Promoter CpGs, with methylation measured by microarray, were classified by the direction of methylation change with normal myeloid maturation. In AML cells, the methylation pattern at maturation-responsive CpG suggested at least partial maturation. Consistent with partial maturation, in gene expression analyses, AML cells expressed high levels of the key lineage-specifying factor CEBPA, but relatively low levels of the key late-differentiation driver CEBPE. In methylation analysis by mass-spectrometry, CEBPE promoter CpG that are usually hypomethylated during granulocyte maturation were significantly hypermethylated in AML cells. Decitabine treatment induced cellular differentiation of AML cells, and the largest methylation decreases were at CpG that are hypomethylated with myeloid maturation, including CEBPE promoter CpG. In contrast, decitabine-treated normal HSC retained immature morphology, and methylation significantly decreased at CpG that are less methylated in immature cells. High expression of lineage-specifying factor and aberrant epigenetic repression of some key late-differentiation genes distinguishes AML cells from normal HSC and could explain the contrasting differentiation and methylation responses to decitabine. PMID:21836612

Sculpturing new muscle phenotypes

NASA Technical Reports Server (NTRS)

Babij, P.; Booth, F. W.

1988-01-01

Changes in the pattern of muscle activity are followed by new patterns of protein synthesis, both in the contractile elements and in the enzymes of energy metabolism. Although the signal transducers have not been identified, techniques of molecular biology have clearly shown that the adaptive responses are the regulated consequence of differential gene expression.

Differentially expressed proteins of soybean (Glycine max) pulvinus in light and dark conditions

USDA-ARS?s Scientific Manuscript database

Soybean leaves (Glycine max) both track and avoid the sun through turgor changes of the pulvinus tissue at the base of leaves. Pulvinar response is known to be affected by both diurnally varying environmental factors and circadian patterns. Differential expression of the proteins between light and d...

Differential gene expression patterns in the autogamous plant Hordeum euclaston (Poaceae).

PubMed

Georg-Kraemer, J E; Ferreira, C A S; Cavalli, S S

2011-02-22

Sib-seedlings of 95 strains of the strictly autogamous grass Hordeum euclaston were analyzed by horizontal polyacrylamide gel electrophoresis for four isoenzyme systems at a specific ontogenetic stage. We found differences in the activity of some genes among individuals of this species. Hence, an ontogenetic analysis was carried out to investigate 12 strains at five ontogenetic stages, to determine the patterns of expression of these genes during development. The differences in the presence versus absence of certain isoenzyme bands may be due to differential regulatory activation in response to environmental differences, as all plants showed the same structural genes, although these genes were active in different tissues and/or times of development. These results indicate the importance of differential gene activation in the metabolic phenotype variability of this strictly autogamous, highly homozygous species. The same structural alleles for isoenzymes showed the active form of the enzymes (phenotypic expression) to be present in different tissues and/or stages of development. Differential isoenzyme gene activation was shown to be directly responsible for the enzymatic variability (metabolic phenotype) presented by the plants, which seem to possess almost no heterozygosis.

Entropy-based divergent and convergent modular pattern reveals additive and synergistic anticerebral ischemia mechanisms.

PubMed

Yu, Yanan; Zhang, Xiaoxu; Li, Bing; Zhang, Yingying; Liu, Jun; Li, Haixia; Chen, Yinying; Wang, Pengqian; Kang, Ruixia; Wu, Hongli; Wang, Zhong

2016-12-01

Module-based network analysis of diverse pharmacological mechanisms is critical to systematically understand combination therapies and disease outcomes. We first constructed drug-target ischemic networks in baicalin, jasminoidin, ursodeoxycholic acid, and their combinations baicalin and jasminoidin as well as jasminoidin and ursodeoxycholic acid groups and identified modules using the entropy-based clustering algorithm. The modules 11, 7, 4, 8 and 3 were identified as baicalin, jasminoidin, ursodeoxycholic acid, baicalin and jasminoidin and jasminoidin and ursodeoxycholic acid-emerged responsive modules, while 12, 8, 15, 17 and 9 were identified as disappeared responsive modules based on variation of topological similarity, respectively. No overlapping differential biological processes were enriched between baicalin and jasminoidin and jasminoidin and ursodeoxycholic acid pure emerged responsive modules, but two were enriched by their co-disappeared responsive modules including nucleotide-excision repair and epithelial structure maintenance. We found an additive effect of baicalin and jasminoidin in a divergent pattern and a synergistic effect of jasminoidin and ursodeoxycholic acid in a convergent pattern on "central hit strategy" of regulating inflammation against cerebral ischemia. The proposed module-based approach may provide us a holistic view to understand multiple pharmacological mechanisms associated with differential phenotypes from the standpoint of modular pharmacology.

Mouse V1 population correlates of visual detection rely on heterogeneity within neuronal response patterns

PubMed Central

Montijn, Jorrit S; Goltstein, Pieter M; Pennartz, Cyriel MA

2015-01-01

Previous studies have demonstrated the importance of the primary sensory cortex for the detection, discrimination, and awareness of visual stimuli, but it is unknown how neuronal populations in this area process detected and undetected stimuli differently. Critical differences may reside in the mean strength of responses to visual stimuli, as reflected in bulk signals detectable in functional magnetic resonance imaging, electro-encephalogram, or magnetoencephalography studies, or may be more subtly composed of differentiated activity of individual sensory neurons. Quantifying single-cell Ca2+ responses to visual stimuli recorded with in vivo two-photon imaging, we found that visual detection correlates more strongly with population response heterogeneity rather than overall response strength. Moreover, neuronal populations showed consistencies in activation patterns across temporally spaced trials in association with hit responses, but not during nondetections. Contrary to models relying on temporally stable networks or bulk signaling, these results suggest that detection depends on transient differentiation in neuronal activity within cortical populations. DOI: http://dx.doi.org/10.7554/eLife.10163.001 PMID:26646184

Content Representation in the Human Medial Temporal Lobe

PubMed Central

Liang, Jackson C.; Wagner, Anthony D.

2013-01-01

Current theories of medial temporal lobe (MTL) function focus on event content as an important organizational principle that differentiates MTL subregions. Perirhinal and parahippocampal cortices may play content-specific roles in memory, whereas hippocampal processing is alternately hypothesized to be content specific or content general. Despite anatomical evidence for content-specific MTL pathways, empirical data for content-based MTL subregional dissociations are mixed. Here, we combined functional magnetic resonance imaging with multiple statistical approaches to characterize MTL subregional responses to different classes of novel event content (faces, scenes, spoken words, sounds, visual words). Univariate analyses revealed that responses to novel faces and scenes were distributed across the anterior–posterior axis of MTL cortex, with face responses distributed more anteriorly than scene responses. Moreover, multivariate pattern analyses of perirhinal and parahippocampal data revealed spatially organized representational codes for multiple content classes, including nonpreferred visual and auditory stimuli. In contrast, anterior hippocampal responses were content general, with less accurate overall pattern classification relative to MTL cortex. Finally, posterior hippocampal activation patterns consistently discriminated scenes more accurately than other forms of content. Collectively, our findings indicate differential contributions of MTL subregions to event representation via a distributed code along the anterior–posterior axis of MTL that depends on the nature of event content. PMID:22275474

Stimulus Set Meaningfulness and Neurophysiological Differentiation: A Functional Magnetic Resonance Imaging Study

PubMed Central

Boly, Melanie; Sasai, Shuntaro; Gosseries, Olivia; Oizumi, Masafumi; Casali, Adenauer; Massimini, Marcello; Tononi, Giulio

2015-01-01

A meaningful set of stimuli, such as a sequence of frames from a movie, triggers a set of different experiences. By contrast, a meaningless set of stimuli, such as a sequence of ‘TV noise’ frames, triggers always the same experience—of seeing ‘TV noise’—even though the stimuli themselves are as different from each other as the movie frames. We reasoned that the differentiation of cortical responses underlying the subject’s experiences, as measured by Lempel-Ziv complexity (incompressibility) of functional MRI images, should reflect the overall meaningfulness of a set of stimuli for the subject, rather than differences among the stimuli. We tested this hypothesis by quantifying the differentiation of brain activity patterns in response to a movie sequence, to the same movie scrambled in time, and to ‘TV noise’, where the pixels from each movie frame were scrambled in space. While overall cortical activation was strong and widespread in all conditions, the differentiation (Lempel-Ziv complexity) of brain activation patterns was correlated with the meaningfulness of the stimulus set, being highest in the movie condition, intermediate in the scrambled movie condition, and minimal for ‘TV noise’. Stimulus set meaningfulness was also associated with higher information integration among cortical regions. These results suggest that the differentiation of neural responses can be used to assess the meaningfulness of a given set of stimuli for a given subject, without the need to identify the features and categories that are relevant to the subject, nor the precise location of selective neural responses. PMID:25970444

Effects of climatic gradients on genetic differentiation of Caragana on the Ordos Plateau, China

Treesearch

Jiuyan Yang; Samuel A. Cushman; Jie Yang; Mingbo Yang; Tiejun Bao

2013-01-01

The genus Caragana (Fabr.) in the Ordos Plateau of Inner Mongolia, China, provides a strong opportunity to investigate patterns of genetic differentiation along steep climatic gradients, and to identify the environmental factors most likely to be responsible for driving the radiation. This study used a factorial, multi-model approach to evaluate alternative hypotheses...

Pulmonary effects of synthetic marijuana: chest radiography and CT findings.

PubMed

Berkowitz, Eugene A; Henry, Travis S; Veeraraghavan, Srihari; Staton, Gerald W; Gal, Anthony A

2015-04-01

The purpose of this article is to present the first chest radiographic and CT descriptions of organizing pneumonia in response to smoking synthetic marijuana. Chest radiographs showed a diffuse miliary-micronodular pattern. Chest CT images showed diffuse centrilobular nodules and tree-in-bud pattern and a histopathologic pattern of organizing pneumonia with or without patchy acute alveolar damage. This distinct imaging pattern should alert radiologists to include synthetic marijuana abuse in the differential diagnosis.

Differential gene expression in response to juvenile hormone analog treatment in the damp-wood termite Hodotermopsis sjostedti (Isoptera, Archotermopsidae).

PubMed

Cornette, Richard; Hayashi, Yoshinobu; Koshikawa, Shigeyuki; Miura, Toru

2013-04-01

Termite societies are characterized by a highly organized division of labor among conspicuous castes, groups of individuals with various morphological specializations. Termite caste differentiation is under control of juvenile hormone (JH), but the molecular mechanism underlying the response to JH and early events triggering caste differentiation are still poorly understood. In order to profile candidate gene expression during early soldier caste differentiation of the damp-wood termite, Hodotermopsis sjostedti, we treated pseudergates (workers) with a juvenile hormone analog (JHA) to induce soldier caste differentiation. We then used Suppressive Subtractive Hybridization to create two cDNA libraries enriched for transcripts that were either up- or downregulated at 24h after treatment. Finally, we used quantitative PCR to confirm temporal expression patterns. Hexamerins represent a large proportion of the genes upregulated following JHA treatment and have an expression pattern that shows roughly an inverse correlation to intrinsic JH titers. This data is consistent with the role of a JH "sink", which was demonstrated for hexamerins in another termite, Reticulitermes flavipes. A putative nuclear protein was also upregulated a few hours after JHA treatment, which suggests a role in the early response to JH and subsequent regulation of transcriptional events associated with soldier caste differentiation. Some digestive enzymes, such as endogenous beta-endoglucanase and chymotrypsin, as well as a protein associated to digestion were identified among genes downregulated after JHA treatment. This suggests that JH may directly influence the pseudergate-specific digestive system. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cicada-inspired cell-instructive nanopatterned arrays

NASA Astrophysics Data System (ADS)

Diu, Ting; Faruqui, Nilofar; Sjöström, Terje; Lamarre, Baptiste; Jenkinson, Howard F.; Su, Bo; Ryadnov, Maxim G.

2014-11-01

Biocompatible surfaces hold key to a variety of biomedical problems that are directly related to the competition between host-tissue cell integration and bacterial colonisation. A saving solution to this is seen in the ability of cells to uniquely respond to physical cues on such surfaces thus prompting the search for cell-instructive nanoscale patterns. Here we introduce a generic rationale engineered into biocompatible, titanium, substrates to differentiate cell responses. The rationale is inspired by cicada wing surfaces that display bactericidal nanopillar patterns. The surfaces engineered in this study are titania (TiO2) nanowire arrays that are selectively bactericidal against motile bacteria, while capable of guiding mammalian cell proliferation according to the type of the array. The concept holds promise for clinically relevant materials capable of differential physico-mechanical responses to cellular adhesion.

Cicada-inspired cell-instructive nanopatterned arrays.

PubMed

Diu, Ting; Faruqui, Nilofar; Sjöström, Terje; Lamarre, Baptiste; Jenkinson, Howard F; Su, Bo; Ryadnov, Maxim G

2014-11-20

Biocompatible surfaces hold key to a variety of biomedical problems that are directly related to the competition between host-tissue cell integration and bacterial colonisation. A saving solution to this is seen in the ability of cells to uniquely respond to physical cues on such surfaces thus prompting the search for cell-instructive nanoscale patterns. Here we introduce a generic rationale engineered into biocompatible, titanium, substrates to differentiate cell responses. The rationale is inspired by cicada wing surfaces that display bactericidal nanopillar patterns. The surfaces engineered in this study are titania (TiO2) nanowire arrays that are selectively bactericidal against motile bacteria, while capable of guiding mammalian cell proliferation according to the type of the array. The concept holds promise for clinically relevant materials capable of differential physico-mechanical responses to cellular adhesion.

Glioblastoma Stem Cells Respond to Differentiation Cues but Fail to Undergo Commitment and Terminal Cell-Cycle Arrest

PubMed Central

Carén, Helena; Stricker, Stefan H.; Bulstrode, Harry; Gagrica, Sladjana; Johnstone, Ewan; Bartlett, Thomas E.; Feber, Andrew; Wilson, Gareth; Teschendorff, Andrew E.; Bertone, Paul; Beck, Stephan; Pollard, Steven M.

2015-01-01

Summary Glioblastoma (GBM) is an aggressive brain tumor whose growth is driven by stem cell-like cells. BMP signaling triggers cell-cycle exit and differentiation of GBM stem cells (GSCs) and, therefore, might have therapeutic value. However, the epigenetic mechanisms that accompany differentiation remain poorly defined. It is also unclear whether cell-cycle arrest is terminal. Here we find only a subset of GSC cultures exhibit astrocyte differentiation in response to BMP. Although overtly differentiated non-cycling astrocytes are generated, they remain vulnerable to cell-cycle re-entry and fail to appropriately reconfigure DNA methylation patterns. Chromatin accessibility mapping identified loci that failed to alter in response to BMP and these were enriched in SOX transcription factor-binding motifs. SOX transcription factors, therefore, may limit differentiation commitment. A similar propensity for cell-cycle re-entry and de-differentiation was observed in GSC-derived oligodendrocyte-like cells. These findings highlight significant obstacles to BMP-induced differentiation as therapy for GBM. PMID:26607953

Integrated analysis of miRNAs and transcriptomes in Aedes albopictus midgut reveals the differential expression profiles of immune-related genes during dengue virus serotype-2 infection.

PubMed

Liu, Yan-Xia; Li, Fen-Xiang; Liu, Zhuan-Zhuan; Jia, Zhi-Rong; Zhou, Yan-He; Zhang, Hao; Yan, Hui; Zhou, Xian-Qiang; Chen, Xiao-Guang

2016-06-01

Mosquito microRNAs (miRNAs) are involved in host-virus interaction, and have been reported to be altered by dengue virus (DENV) infection in Aedes albopictus (Diptera: Culicidae). However, little is known about the molecular mechanisms of Aedes albopictus midgut-the first organ to interact with DENV-involved in its resistance to DENV. Here we used high-throughput sequencing to characterize miRNA and messenger RNA (mRNA) expression patterns in Aedes albopictus midgut in response to dengue virus serotype 2. A total of three miRNAs and 777 mRNAs were identified to be differentially expressed upon DENV infection. For the mRNAs, we identified 198 immune-related genes and 31 of them were differentially expressed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses also showed that the differentially expressed immune-related genes were involved in immune response. Then the differential expression patterns of six immune-related genes and three miRNAs were confirmed by real-time reverse transcription polymerase chain reaction. Furthermore, seven known miRNA-mRNA interaction pairs were identified by aligning our two datasets. These analyses of miRNA and mRNA transcriptomes provide valuable information for uncovering the DENV response genes and provide a basis for future study of the resistance mechanisms in Aedes albopictus midgut. © 2016 Institute of Zoology, Chinese Academy of Sciences.

Gender-specificity of solitary and dyadic sexual desire among gynephilic and androphilic women and men.

PubMed

Dawson, Samantha J; Chivers, Meredith L

2014-04-01

Incentive motivation theory proposes that sexual desire emerges from sexual arousal, and is triggered by sexually competent stimuli. Research demonstrates gender and sexual orientation differences in the features that contribute to the competency of sexual stimuli. Men's and gynephilic women's genital arousal tends to be gender-specific with preferred gender eliciting significantly greater genital arousal than nonpreferred gender. In contrast, stimuli depicting preferred and nonpreferred gender elicit similar degrees of genital arousal among androphilic women, termed a gender-nonspecific pattern. Given these differences in the features that elicit a sexual response, and that sexual desire is proposed to emerge from sexual arousal, the question remains as to whether sexual desire would emerge only through exposure to preferred stimuli or whether patterns of responsive desire would parallel those observed for genital arousal. The study aims to examine patterns of dyadic and solitary sexual desire in response to stimuli differing in incentive value. Thirty androphilic women, 21 gynephilic women, 21 gynephilic men, and 16 androphilic men participated in a sexual psychophysiological session. Participants viewed sexual stimuli that varied the gender of the actors and the intensity of sexual activities depicted. Participants reported their degree of desire for sex with a partner (dyadic desire) and desire to masturbate (solitary desire), before and after each film. Men and gynephilic women exhibited gender-specific patterns of sexual desire. Androphilic women's dyadic desire showed significantly less differentiation between genders, and their solitary desire did not differentiate at all. No gender difference was observed for either type of desire. All groups reported greater desire as stimulus intensity increased. Gender-nonspecific sexual response is not limited to the sexual arousal patterns of androphilic women, but extends to include responsive sexual desire. Men and gynephilic women, however, show gender-specific responsive sexual desire that parallels their sexual arousal patterns. © 2014 International Society for Sexual Medicine.

Environmental and Historical Determinants of Patterns of Genetic Differentiation in Wild Soybean (Glycine soja Sieb. et Zucc)

PubMed Central

He, Shui-Lian; Wang, Yun-Sheng; Li, De-Zhu; Yi, Ting-Shuang

2016-01-01

Wild soybean, the direct progenitor of cultivated soybean, inhabits a wide distribution range across the mainland of East Asia and the Japanese archipelago. A multidisciplinary approach combining analyses of population genetics based on 20 nuclear microsatellites and one plastid locus were applied to reveal the genetic variation of wild soybean, and the contributions of geographical, environmental factors and historic climatic change on its patterns of genetic differentiation. High genetic diversity and significant genetic differentiation were revealed in wild soybean. Wild soybean was inferred to be limited to southern and central China during the Last Glacial Maximum (LGM) and experienced large-scale post-LGM range expansion into northern East Asia. A substantial northward range shift has been predicted to occur by the 2080s. A stronger effect of isolation by environment (IBE) versus isolation by geographical distance (IBD) was found for genetic differentiation in wild soybean, which suggested that environmental factors were responsible for the adaptive eco-geographical differentiation. This study indicated that IBE and historical climatic change together shaped patterns of genetic variation and differentiation of wild soybean. Different conservation measures should be implemented on different populations according to their adaptive potential to future changes in climate and human-induced environmental changes. PMID:26952904

Entropy-based divergent and convergent modular pattern reveals additive and synergistic anticerebral ischemia mechanisms

PubMed Central

Yu, Yanan; Zhang, Xiaoxu; Li, Bing; Zhang, Yingying; Liu, Jun; Li, Haixia; Chen, Yinying; Wang, Pengqian; Kang, Ruixia; Wu, Hongli

2016-01-01

Module-based network analysis of diverse pharmacological mechanisms is critical to systematically understand combination therapies and disease outcomes. We first constructed drug-target ischemic networks in baicalin, jasminoidin, ursodeoxycholic acid, and their combinations baicalin and jasminoidin as well as jasminoidin and ursodeoxycholic acid groups and identified modules using the entropy-based clustering algorithm. The modules 11, 7, 4, 8 and 3 were identified as baicalin, jasminoidin, ursodeoxycholic acid, baicalin and jasminoidin and jasminoidin and ursodeoxycholic acid-emerged responsive modules, while 12, 8, 15, 17 and 9 were identified as disappeared responsive modules based on variation of topological similarity, respectively. No overlapping differential biological processes were enriched between baicalin and jasminoidin and jasminoidin and ursodeoxycholic acid pure emerged responsive modules, but two were enriched by their co-disappeared responsive modules including nucleotide-excision repair and epithelial structure maintenance. We found an additive effect of baicalin and jasminoidin in a divergent pattern and a synergistic effect of jasminoidin and ursodeoxycholic acid in a convergent pattern on “central hit strategy” of regulating inflammation against cerebral ischemia. The proposed module-based approach may provide us a holistic view to understand multiple pharmacological mechanisms associated with differential phenotypes from the standpoint of modular pharmacology. PMID:27480252

Basic emotions induced by odorants: a new approach based on autonomic pattern results.

PubMed

Vernet-Maury, E; Alaoui-Ismaïli, O; Dittmar, A; Delhomme, G; Chanel, J

1999-02-15

The aim of this study was to link the effects of odorants with the emotional process, through autonomic nervous system (ANS) responses. Taking Ekman's data and our previous results into account, we tried to verify a possible evocation by odorants of some basic emotions, i.e. anger, fear, sadness, surprise, disgust and happiness. The question investigated was: would it be possible to associate any of these emotions with a pattern of autonomic responses? A total of 15 subjects inhaled five odorants: lavender, ethyl aceto acetate, camphor, acetic acid and butyric acid acting as olfactory stimuli. After inhaling the odorant, subjects were requested to fill out an 11-point hedonic scale to rate its 'pleasantness' vs. 'unpleasantness'. ANS parameters monitored were skin potential and resistance, skin blood flow and temperature, instantaneous respiratory frequency and instantaneous heart rate. Simultaneous recording of these six autonomic parameters permitted the analysis of phasic responses through specific ANS patterns. An analysis of variance made it possible to differentiate among the five odorants. Two-by-two odorant comparisons for autonomic responses using Tukey's HSD multiple comparison test only permitted differentiation between 'pleasant' and 'unpleasant' odors. Camphor was differentiated from both types. For instance, long duration responses were associated with 'unpleasant' odors whereas camphor elicited intermediate responses. Taking into account each subject's preferential channel, it was possible to associate each ANS pattern with a basic emotion by means of a decision tree. The computation of subjects' responses made it possible to associate an odorant with a basic emotion, over the whole group: lavender elicited mostly 'happiness', as did, to a lesser degree ethyl aceto acetate; camphor induced either 'happiness', 'surprise' or 'sadness' according to subjects' past histories; butyric and acetic acids mainly induced negative emotions: 'anger' and 'disgust'. A high correlation was evidenced between subjects' hedonic evaluation and autonomic estimation of basic emotions. These results obtained from 15 subjects were compared to those observed in two similar experiments. These approaches showed comparable results. Thus, more than 60 subjects showed similar autonomic responses which can be transcribed into basic emotions. Thus, a multiparametric autonomic analysis allows the identification of the quality of the response, i.e. the type of basic emotion in addition to the intensity.

Differential responses of Bolivian timber species to prescribed fire and other gap treatments

Treesearch

Debora K. Kennard; Francis E. Putz

2005-01-01

We followed the establishment and growth response of 13 commercial tree species to canopy opening, above-ground biomass removal, and experimental burns of low and high intensities in a lowland dry forest in Bolivia. Three patterns of response to treatments were observed among the most abundant commercial tree species. (1) Shade-intolerant species regenerated mostly...

Regulation of cell-fate determination in Dictyostelium.

PubMed

Brown, J M; Firtel, R A

1999-12-15

A key step in the development of all multicellular organisms is the differentiation of specialized cell types. The eukaryotic microorganism Dictyostelium discoideum provides a unique experimental system for studying cell-type determination and spatial patterning in a developing multicellular organism. Unlike metazoans, which become multicellular by undergoing many rounds of cell division after fertilization of an egg, the social amoeba Dictyostelium achieves multicellularity by the aggregation of approximately 10(5) cells in response to nutrient depletion. Following aggregation, cell-type differentiation and morphogenesis result in a multicellular organism with only a few cell types that exhibit a defined patterning along the anterior-posterior axis of the organism. Analysis of the mechanisms that control these processes is facilitated by the relative simplicity of Dictyostelium development and the availability of molecular, genetic, and cell biological tools. Interestingly, analysis has shown that many molecules that play integral roles in the development of higher eukaryotes, such as PKA, STATs, and GSK-3, are also essential for cell-type differentiation and patterning in Dictyostelium. The role of these and other signaling pathways in the induction, maintenance, and patterning of cell types during Dictyostelium development is discussed.

Differential spatial activity patterns of acupuncture by a machine learning based analysis

NASA Astrophysics Data System (ADS)

You, Youbo; Bai, Lijun; Xue, Ting; Zhong, Chongguang; Liu, Zhenyu; Tian, Jie

2011-03-01

Acupoint specificity, lying at the core of the Traditional Chinese Medicine, underlies the theoretical basis of acupuncture application. However, recent studies have reported that acupuncture stimulation at nonacupoint and acupoint can both evoke similar signal intensity decreases in multiple regions. And these regions were spatially overlapped. We used a machine learning based Support Vector Machine (SVM) approach to elucidate the specific neural response pattern induced by acupuncture stimulation. Group analysis demonstrated that stimulation at two different acupoints (belong to the same nerve segment but different meridians) could elicit distinct neural response patterns. Our findings may provide evidence for acupoint specificity.

Method translation and full metadata transfer from thermal to differential flow modulated comprehensive two dimensional gas chromatography: Profiling of suspected fragrance allergens.

PubMed

Cordero, Chiara; Rubiolo, Patrizia; Reichenbach, Stephen E; Carretta, Andrea; Cobelli, Luigi; Giardina, Matthew; Bicchi, Carlo

2017-01-13

The possibility to transfer methods from thermal to differential-flow modulated comprehensive two-dimensional gas chromatographic (GC×GC) platforms is of high interest to improve GC×GC flexibility and increase the compatibility of results from different platforms. The principles of method translation are here applied to an original method, developed for a loop-type thermal modulated GC×GC-MS/FID system, suitable for quali-quantitative screening of suspected fragrance allergens. The analysis conditions were translated to a reverse-injection differential flow modulated platform (GC×2GC-MS/FID) with a dual-parallel secondary column and dual detection. The experimental results, for a model mixture of suspected volatile allergens and for raw fragrance mixtures of different composition, confirmed the feasibility of translating methods by preserving 1 D elution order, as well as the relative alignment of resulting 2D peak patterns. A correct translation produced several benefits including an effective transfer of metadata (compound names, MS fragmentation pattern, response factors) by automatic template transformation and matching from the original/reference method to its translated counterpart. The correct translation provided: (a) 2D pattern repeatability, (b) MS fragmentation pattern reliability for identity confirmation, and (c) comparable response factors and quantitation accuracy within a concentration range of three orders of magnitude. The adoption of a narrow bore (i.e. 0.1mm d c ) first-dimension column to operate under close-to-optimal conditions with the differential-flow modulation GC×GC platform was also advantageous in halving the total analysis under the translated conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Ketamine induces a robust whole-brain connectivity pattern that can be differentially modulated by drugs of different mechanism and clinical profile.

PubMed

Joules, R; Doyle, O M; Schwarz, A J; O'Daly, O G; Brammer, M; Williams, S C; Mehta, M A

2015-11-01

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has been studied in relation to the glutamate hypothesis of schizophrenia and increases dissociation, positive and negative symptom ratings. Ketamine effects brain function through changes in brain activity; these activity patterns can be modulated by pre-treatment of compounds known to attenuate the effects of ketamine on glutamate release. Ketamine also has marked effects on brain connectivity; we predicted that these changes would also be modulated by compounds known to attenuate glutamate release. Here, we perform task-free pharmacological magnetic resonance imaging (phMRI) to investigate the functional connectivity effects of ketamine in the brain and the potential modulation of these effects by pre-treatment of the compounds lamotrigine and risperidone, compounds hypothesised to differentially modulate glutamate release. Connectivity patterns were assessed by combining windowing, graph theory and multivariate Gaussian process classification. We demonstrate that ketamine has a robust effect on the functional connectivity of the human brain compared to saline (87.5 % accuracy). Ketamine produced a shift from a cortically centred, to a subcortically centred pattern of connections. This effect is strongly modulated by pre-treatment with risperidone (81.25 %) but not lamotrigine (43.75 %). Based on the differential effect of these compounds on ketamine response, we suggest the observed connectivity effects are primarily due to NMDAR blockade rather than downstream glutamatergic effects. The connectivity changes contrast with amplitude of response for which no differential effect between pre-treatments was detected, highlighting the necessity of these techniques in forming an informed view of the mechanistic effects of pharmacological compounds in the human brain.

cDNA-AFLP analysis reveals differential gene expression in response to salt stress in foxtail millet (Setaria italica L.).

PubMed

Jayaraman, Ananthi; Puranik, Swati; Rai, Neeraj Kumar; Vidapu, Sudhakar; Sahu, Pranav Pankaj; Lata, Charu; Prasad, Manoj

2008-11-01

Plant growth and productivity are affected by various abiotic stresses such as heat, drought, cold, salinity, etc. The mechanism of salt tolerance is one of the most important subjects in plant science as salt stress decreases worldwide agricultural production. In our present study we used cDNA-AFLP technique to compare gene expression profiles of a salt tolerant and a salt-sensitive cultivar of foxtail millet (Seteria italica) in response to salt stress to identify early responsive differentially expressed transcripts accumulated upon salt stress and validate the obtained result through quantitative real-time PCR (qRT-PCR). The expression profile was compared between a salt tolerant (Prasad) and susceptible variety (Lepakshi) of foxtail millet in both control condition (L0 and P0) and after 1 h (L1 and P1) of salt stress. We identified 90 transcript-derived fragments (TDFs) that are differentially expressed, out of which 86 TDFs were classified on the basis of their either complete presence or absence (qualitative variants) and 4 on differential expression pattern levels (quantitative variants) in the two varieties. Finally, we identified 27 non-redundant differentially expressed cDNAs that are unique to salt tolerant variety which represent different groups of genes involved in metabolism, cellular transport, cell signaling, transcriptional regulation, mRNA splicing, seed development and storage, etc. The expression patterns of seven out of nine such genes showed a significant increase of differential expression in tolerant variety after 1 h of salt stress in comparison to salt-sensitive variety as analyzed by qRT-PCR. The direct and indirect relationship of identified TDFs with salinity tolerance mechanism is discussed.

Distribution patterns in the native vascular flora of Iceland.

PubMed

Wasowicz, Pawel; Pasierbiński, Andrzej; Przedpelska-Wasowicz, Ewa Maria; Kristinsson, Hörður

2014-01-01

The aim of our study was to reveal biogeographical patterns in the native vascular flora of Iceland and to define ecological factors responsible for these patterns. We analysed dataset of more than 500,000 records containing information on the occurrence of vascular plants. Analysis of ecological factors included climatic (derived from WORLDCLIM data), topographic (calculated from digital elevation model) and geological (bedrock characteristics) variables. Spherical k-means clustering and principal component analysis were used to detect biogeographical patterns and to study the factors responsible for them. We defined 10 biotic elements exhibiting different biogeographical patterns. We showed that climatic (temperature-related) and topographic variables were the most important factors contributing to the spatial patterns within the Icelandic vascular flora and that these patterns are almost completely independent of edaphic factors (bedrock type). Our study is the first one to analyse the biogeographical differentiation of the native vascular flora of Iceland.

The Specificity of Women's Sexual Response and Its Relationship with Sexual Orientations: A Review and Ten Hypotheses.

PubMed

Chivers, Meredith L

2017-07-01

Category-specific sexual response describes a pattern wherein the individual shows significantly greater responses to preferred versus nonpreferred categories of sexual stimuli; this pattern is described as gender specific for sexual orientation to gender, or gender nonspecific if lacking response differentiation by gender cues. Research on the gender specificity of women's sexual response has consistently produced sexual orientation effects, such that androphilic women (sexually attracted to adult males) typically show gender-nonspecific patterns of genital response and gynephilic women (sexually attracted to adult females) show more gender-specific responses. As research on the category specificity of sexual response has grown, this pattern has also been observed for other measures of sexual response. In this review, I use the Incentive Motivation and Information Processing Models as complementary frameworks to organize the empirical literature examining the gender specificity of women's sexual response at each stage of sexual stimulus processing and response. Collectively, these data disconfirm models of sexual orientation that equate androphilic women's sexual attractions with their sexual responses to sexual stimuli. I then discuss 10 hypotheses that might explain variability in the specificity of sexual response among androphilic and gynephilic women, and conclude with recommendations for future research on the (non)specificity of sexual response.

Variation in functional responses to water stress and differentiation between natural allopolyploid populations in the Brachypodium distachyon species complex.

PubMed

Martínez, Luisa M; Fernández-Ocaña, Ana; Rey, Pedro J; Salido, Teresa; Amil-Ruiz, Francisco; Manzaneda, Antonio J

2018-06-08

Some polyploid species show enhanced physiological tolerance to drought compared with their progenitors. However, very few studies have examined the consistency of physiological drought response between genetically differentiated natural polyploid populations, which is key to evaluation of the importance of adaptive evolution after polyploidization in those systems where drought exerts a selective pressure. A comparative functional approach was used to investigate differentiation of drought-tolerance-related traits in the Brachypodium species complex, a model system for grass polyploid adaptive speciation and functional genomics that comprises three closely related annual species: the two diploid parents, B. distachyon and B. stacei, and the allotetraploid derived from them, B. hybridum. Differentiation of drought-tolerance-related traits between ten genetically distinct B. hybridum populations and its ecological correlates was further analysed. The functional drought response is overall well differentiated between Brachypodium species. Brachypodium hybridum allotetraploids showed a transgressive expression pattern in leaf phytohormone content in response to drought. In contrast, other B. hybridum physiological traits correlated to B. stacei ones. Particularly, proline and water content were the traits that best discriminated these species from B. distachyon under drought. After polyploid formation and/or colonization, B. hybridum populations have adaptively diverged physiologically and genetically in response to variations in aridity.

Low power, lightweight vapor sensing using arrays of conducting polymer composite chemically-sensitive resistors

NASA Technical Reports Server (NTRS)

Ryan, M. A.; Lewis, N. S.

2001-01-01

Arrays of broadly responsive vapor detectors can be used to detect, identify, and quantify vapors and vapor mixtures. One implementation of this strategy involves the use of arrays of chemically-sensitive resistors made from conducting polymer composites. Sorption of an analyte into the polymer composite detector leads to swelling of the film material. The swelling is in turn transduced into a change in electrical resistance because the detector films consist of polymers filled with conducting particles such as carbon black. The differential sorption, and thus differential swelling, of an analyte into each polymer composite in the array produces a unique pattern for each different analyte of interest, Pattern recognition algorithms are then used to analyze the multivariate data arising from the responses of such a detector array. Chiral detector films can provide differential detection of the presence of certain chiral organic vapor analytes. Aspects of the spaceflight qualification and deployment of such a detector array, along with its performance for certain analytes of interest in manned life support applications, are reviewed and summarized in this article.

Histone acetylation is associated with differential gene expression in the rapid and robust memory CD8+ T-cell response

PubMed Central

Fann, Monchou; Godlove, Jason M.; Catalfamo, Marta; Wood, William H.; Chrest, Francis J.; Chun, Nicholas; Granger, Larry; Wersto, Robert; Madara, Karen; Becker, Kevin; Henkart, Pierre A.; Weng, Nan-ping

2006-01-01

To understand the molecular basis for the rapid and robust memory T-cell responses, we examined gene expression and chromatin modification by histone H3 lysine 9 (H3K9) acetylation in resting and activated human naive and memory CD8+ T cells. We found that, although overall gene expression patterns were similar, a number of genes are differentially expressed in either memory or naive cells in their resting and activated states. To further elucidate the basis for differential gene expression, we assessed the role of histone H3K9 acetylation in differential gene expression. Strikingly, higher H3K9 acetylation levels were detected in resting memory cells, prior to their activation, for those genes that were differentially expressed following activation, indicating that hyperacetylation of histone H3K9 may play a role in selective and rapid gene expression of memory CD8+ T cells. Consistent with this model, we showed that inducing high levels of H3K9 acetylation resulted in an increased expression in naive cells of those genes that are normally expressed differentially in memory cells. Together, these findings suggest that differential gene expression mediated at least in part by histone H3K9 hyperacetylation may be responsible for the rapid and robust memory CD8+ T-cell response. PMID:16868257

Comparative epigenetic influence of autologous versus fetal bovine serum on mesenchymal stem cells through in vitro osteogenic and adipogenic differentiation

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

Fani, Nesa; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran

Mesenchymal stem cells (MSCs) derived from bone marrow (BM) represents a useful source of adult stem cells for cell therapy and tissue engineering. MSCs are present at a low frequency in the BM; therefore expansion is necessary before performing clinical studies. Fetal bovine serum (FBS) as a nutritional supplement for in vitro culture of MSCs is a suitable additive for human cell culture, but not regarding subsequent use of these cells for clinical treatment of human patients due to the risk of viral and prion transmission as well as xenogeneic immune responses after transplantation. Recently, autologous serum (AS) has beenmore » as a supplement to replace FBS in culture medium. We compared the effect of FBS versus AS on the histone modification pattern of MSCs through in vitro osteogenesis and adipogenesis. Differentiation of stem cells under various serum conditions to a committed state involves global changes in epigenetic patterns that are critically determined by chromatin modifications. Chromatin immunoprecipitation (ChIP) coupled with real-time PCR showed significant changes in the acetylation and methylation patterns in lysine 9 (Lys9) of histone H3 on the regulatory regions of stemness (Nanog, Sox2, Rex1), osteogenic (Runx2, Oc, Sp7) and adipogenic (Ppar-γ, Lpl, adiponectin) marker genes in undifferentiated MSCs, FBS and AS. All epigenetic changes occurred in a serum dependent manner which resulted in higher expression level of stemness genes in undifferentiated MSCs compared to differentiated MSCs and increased expression levels of osteogenic genes in AS compared to FBS. Adipogenic genes showed greater expression in FBS compared to AS. These findings have demonstrated the epigenetic influence of serum culture conditions on differentiation potential of MSCs, which suggest that AS is possibly more efficient serum for osteogenic differentiation of MSCs in cell therapy purposes. - Highlights: • Bone marrow derived MSC could proliferate in AS as well as in FBS. • Different serum conditions influence epigentic patterns of genes. • Osteogenic genes specifically up-regulate in AS in response to differentiation signals.« less

Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

NASA Astrophysics Data System (ADS)

Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

2016-06-01

Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

TLR10 suppresses the activation and differentiation of monocytes with effects on DC-mediated adaptive immune responses

PubMed Central

Hess, Nicholas J.; Felicelli, Christopher; Grage, Jennifer; Tapping, Richard I.

2017-01-01

TLRs are important pattern-recognition receptors involved in the activation of innate immune responses against foreign pathogens. TLR10 is the only TLR family member without a known ligand, signaling pathway, or clear cellular function. Previous work has shown that TLR10 suppresses proinflammatory cytokine production in response to TLR agonists in a mixed human mononuclear cell population. We report that TLR10 is preferentially expressed on monocytes and suppresses proinflammatory cytokine production resulting from either TLR or CD40 stimulation. TLR10 engagement affects both the MAPK and Akt signaling pathways, leading to changes in the transcriptome of isolated human monocytes. Differentiation of monocytes into dendritic cells in the presence of an αTLR10 mAb reduced the expression of maturation markers and the induction of proinflammatory cytokines, again in response to either TLR or CD40 stimulation. Finally, in coculture experiments, TLR10 differentiated dendritic cells exhibited a decreased capacity to activate T cells as measured by IL-2 and IFN-γ production. These data demonstrate that TLR10 is a novel regulator of innate immune responses and of the differentiation of primary human monocytes into effective dendritic cells. PMID:28235773

Is Serotonin Transporter Genotype Associated with Epigenetic Susceptibility or Vulnerability? Examination of the Impact of SES Risk on African American Youth

PubMed Central

Beach, S. R. H.; Brody, G. H.; Lei, M.K.; Kim, S.; Cui, J.

2014-01-01

We hypothesized that presence of the s allele in the promoter region of the serotonin transporter (5-HTTLR) would moderate the effect of early cumulative SES risk on epigenetic change among African American youth. Contrasting hypotheses regarding the shape of the interaction effect were generated using vulnerability and susceptibility frameworks and applied to data from a sample of 388 African American youth. Early, cumulative SES risk assessed at 11–13 years based on parent report interacted with presence of the s allele to predict differential methylation assessed at age 19. Across multiple tests, a differential susceptibility perspective rather than a diathesis stress framework best fit the data for genes associated with depression, consistently demonstrating greater epigenetic response to early cumulative SES risk among s allele carriers. A pattern consistent with greater impact among s allele carriers also was observed using all CpG sites across the genome that were differentially affected by early cumulative SES risk. We conclude that the s allele is associated with increased responsiveness to early cumulative SES risk among African American youth, leading to epigenetic divergence for depression-related genes in response to exposure to heightened SES risk among s allele carriers in a “for better” or “for worse” pattern. PMID:24438855

A Mixture Rasch Model with a Covariate: A Simulation Study via Bayesian Markov Chain Monte Carlo Estimation

ERIC Educational Resources Information Center

Dai, Yunyun

2013-01-01

Mixtures of item response theory (IRT) models have been proposed as a technique to explore response patterns in test data related to cognitive strategies, instructional sensitivity, and differential item functioning (DIF). Estimation proves challenging due to difficulties in identification and questions of effect size needed to recover underlying…

For Which Boys and Which Girls Are Reading Assessment Items Biased Against? Detection of Differential Item Functioning in Heterogeneous Gender Populations

ERIC Educational Resources Information Center

Grover, Raman K.; Ercikan, Kadriye

2017-01-01

In gender differential item functioning (DIF) research it is assumed that all members of a gender group have similar item response patterns and therefore generalizations from group level to subgroup and individual levels can be made accurately. However DIF items do not necessarily disadvantage every member of a gender group to the same degree,…

Understanding and responding the students in learning mathematics through the differentiated instruction

NASA Astrophysics Data System (ADS)

Hapsari, T.; Darhim; Dahlan, J. A.

2018-05-01

This research discusses the differentiated instruction, a mathematic learning which is as expected by the students in connection with the differentiated instruction itself, its implementation, and the students’ responses. This research employs a survey method which involves 62 students as the research respondents. The mathematics learning types required by the students and their responses to the differentiated instruction are examined through questionnaire and interview. The mathematics learning types in orderly required by the students, from the highest frequency cover the easily understood instructions, slowly/not rushing teaching, fun, not complicated, interspersed with humour, various question practices, not too serious, and conducive class atmosphere for the instructions. Implementing the differentiated instruction is not easy. The teacher should be able to constantly assess the students, s/he should have good knowledge of relevant materials and instructions, and properly prepare the instructions, although it is time-consuming. The differentiated instruction is implemented on the instructions of numerical pattern materials. The strategies implemented are flexible grouping, tiered assignment, and compacting. The students positively respond the differentiated learning instruction that they become more motivated and involved in the instruction.

Effects of cyproterone acetate on sexual arousal patterns of pedophiles.

PubMed

Bradford, J M; Pawlak, A

1993-12-01

The antiandrogen treatment of sexual offenders has been shown to reduce the recidivism rate. The mechanism of action has been assumed to be through asexualization with its secondary effects on sexual behavior. This study shows that the mechanism may be more complex and may involve a differential effect on sexual arousal patterns. Treatment responses may differ in high and low plasma testosterone groups.

Transcriptional responses of metallothionein gene to different stress factors in Pacific abalone (Haliotis discus hannai).

PubMed

Lee, Sang Yoon; Nam, Yoon Kwon

2016-11-01

A novel metallothionein (MT) gene from the Pacific abalone H. discus hannai was characterized and its mRNA expression patterns (tissue distribution, developmental expression and differential expression in responsive to various in vivo stimulatory treatments) were examined. Abalone MT shares conserved structural features with previously known gastropod orthologs at both genomic (i.e., tripartite organization) and amino acid (conserved Cys motifs) levels. The 5'-flanking regulatory region of abalone MT gene displayed various transcription factor binding motifs particularly including ones related with metal regulation and stress/immune responses. Tissue distribution and basal expression patterns of MT mRNAs indicated a potential association between ovarian MT expression and sexual maturation. Developmental expression pattern suggested the maternal contribution of MT mRNAs to embryonic and early larval developments. Abalone MT mRNAs could be significantly induced by various heavy metals in different tissues (gill, hepatopancreas, muscle and hemocyte) in a tissue- and/or metal-dependent fashion. In addition, the abalone MT gene was highly modulated in responsive to other non-metal, stimulatory treatments such as immune challenge (LPS, polyI:C and bacterial injections), hypoxia (decrease from normoxia 8 ppm-2 ppm), thermal elevation (increase from 20 °C to 30 °C), and xenobiotic exposure (250 ppb of 17α-ethynylestradiol and 0.25 ppb of 2,3,7,8-tetrachlorodibenzodioxin) where differential expression patterns were toward either up- or down-regulation depending on types of stimulations and tissues examined. Taken together, our results highlight that MT is a multifunctional effector playing in wide criteria of cellular pathways especially associated with development and stress responses in this abalone species. Copyright © 2016 Elsevier Ltd. All rights reserved.

Osteoblast-like cell response to macro- and micro-patterned carbon scaffolds obtained from the sea rush Juncus maritimus.

PubMed

López-Álvarez, M; Pereiro, I; Serra, J; de Carlos, A; González, P

2011-08-01

Carbon scaffolds with a directional patterned surface were obtained by pyrolysis of the sea rush Juncus maritimus. The structure of the scaffolds was investigated using scanning electron microscopy, mercury porosimetry and interferometric profilometry. X-ray diffraction and x-ray fluorescence were the techniques used for their chemical characterization. The alignment and differentiation of pre-osteoblasts (MC3T3-E1 cell line) incubated on the patterned scaffolds were evaluated by scanning electron microscopy, confocal laser scanning microscopy and by the quantification of the phosphatase alkaline activity and the osteocalcin synthesis. It was found that pyrolysis at 500 °C preserved and even enhanced the natural macro- and micro-patterning of the plant. The results obtained for porosity and chemical composition validated these structures as viable scaffolds for tissue engineering applications. Finally, the patterned surface was confirmed to promote the oriented growth of the pre-osteoblasts MC3T3-E1, not only after short periods of incubation (hours) but also after longer ones (several weeks). The quantification of the cell differentiation markers together with the evaluation of the cell layer morphology up to 28 days of incubation confirmed the differentiation of MC3T3-E1 cells to osteoblasts. © 2011 IOP Publishing Ltd

The Effects of Gender and Relationship Context Cues on Responsive Sexual Desire in Exclusively and Predominantly Androphilic Women and Gynephilic Men.

PubMed

Timmers, Amanda D; Dawson, Samantha J; Chivers, Meredith L

2018-04-20

Sexual desire may be "responsive," emerging from sexual arousal to sexually competent cues. Cues that elicit sexual arousal and desire differ, however, by gender and direction of sexual attractions. Further, relationship context cues are thought to be important for responsive desire, but this has not been tested directly. The current study examined gynephilic men's (n = 27) and exclusively (n = 23) and predominantly (n = 17) androphilic women's dyadic and solitary responsive sexual desire, as well as genital and self-reported arousal, to audio narratives varying by gender (male, female) of the sexual partner and relationship context (stranger, friend, long-term relationship). Consistent with previous literature, gynephilic men's solitary and dyadic desire were gender-specific (greater to female than to male sexual partners). Exclusively androphilic women's dyadic desire differentiated less to cues of gender than gynephilic men's, and their solitary desire did not differentiate by gender cues at all, replicating previous research. Androphilic women with some gynephilia reported a gender-nonspecific pattern of dyadic and solitary desire (i.e., responsive desire to both male and female narratives). No effect of relationship context was found for any groups. Results suggest that responsive sexual desire may be more closely associated with self-reported than genital arousal patterns.

Epigenetic dysregulation of the dopamine system in diet-induced obesity.

PubMed

Vucetic, Zivjena; Carlin, Jesse Lea; Totoki, Kathy; Reyes, Teresa M

2012-03-01

Chronic intake of high-fat (HF) diet is known to alter brain neurotransmitter systems that participate in the central regulation of food intake. Dopamine (DA) system changes in response to HF diet have been observed in the hypothalamus, important in the homeostatic control of food intake, as well as within the central reward circuitry [ventral tegmental area (VTA), nucleus accumbens (NAc), and pre-frontal cortex (PFC)], critical for coding the rewarding properties of palatable food and important in hedonically driven feeding behavior. Using a mouse model of diet-induced obesity (DIO), significant alterations in the expression of DA-related genes were documented in adult animals, and the general pattern of gene expression changes was opposite within the hypothalamus versus the reward circuitry (increased vs. decreased, respectively). Differential DNA methylation was identified within the promoter regions of tyrosine hydroxylase (TH) and dopamine transporter (DAT), and the pattern of this response was consistent with the pattern of gene expression. Behaviors consistent with increased hypothalamic DA and decreased reward circuitry DA were observed. These data identify differential DNA methylation as an epigenetic mechanism linking the chronic intake of HF diet with altered DA-related gene expression, and this response varies by brain region and DNA sequence. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Mechanisms of macroevolution: polyphagous plasticity in butterfly larvae revealed by RNA-Seq.

PubMed

de la Paz Celorio-Mancera, Maria; Wheat, Christopher W; Vogel, Heiko; Söderlind, Lina; Janz, Niklas; Nylin, Sören

2013-10-01

Transcriptome studies of insect herbivory are still rare, yet studies in model systems have uncovered patterns of transcript regulation that appear to provide insights into how insect herbivores attain polyphagy, such as a general increase in expression breadth and regulation of ribosomal, digestion- and detoxification-related genes. We investigated the potential generality of these emerging patterns, in the Swedish comma, Polygonia c-album, which is a polyphagous, widely-distributed butterfly. Urtica dioica and Ribes uva-crispa are hosts of P. c-album, but Ribes represents a recent evolutionary shift onto a very divergent host. Utilizing the assembled transcriptome for read mapping, we assessed gene expression finding that caterpillar life-history (i.e. 2nd vs. 4th-instar regulation) had a limited influence on gene expression plasticity. In contrast, differential expression in response to host-plant identified genes encoding serine-type endopeptidases, membrane-associated proteins and transporters. Differential regulation of genes involved in nucleic acid binding was also observed suggesting that polyphagy involves large scale transcriptional changes. Additionally, transcripts coding for structural constituents of the cuticle were differentially expressed in caterpillars in response to their diet indicating that the insect cuticle may be a target for plant defence. Our results state that emerging patterns of transcript regulation from model species appear relevant in species when placed in an evolutionary context. © 2013 John Wiley & Sons Ltd.

Hantaviruses induce cell type- and viral species-specific host microRNA expression signatures

PubMed Central

Shin, Ok Sarah; Kumar, Mukesh; Yanagihara, Richard; Song, Jin-Won

2014-01-01

The mechanisms of hantavirus-induced modulation of host cellular immunity remain poorly understood. Recently, microRNAs (miRNAs) have emerged as a class of essential regulators of host immune response genes. To ascertain if differential host miRNA expression toward representative hantavirus species correlated with immune response genes, miRNA expression profiles were analyzed in human endothelial cells, macrophages and epithelial cells infected with pathogenic and nonpathogenic rodent- and shrew-borne hantaviruses. Distinct miRNA expression profiles were observed in a cell type- and viral species-specific pattern. A subset of miRNAs, including miR-151-5p and miR-1973, were differentially expressed between Hantaan virus and Prospect Hill virus. Pathway analyses confirmed that the targets of selected miRNAs were associated with inflammatory responses and innate immune receptor-mediated signaling pathways. Our data suggest that differential immune responses following hantavirus infection may be regulated in part by cellular miRNA through dysregulation of genes critical to the inflammatory process. PMID:24074584

Control of somite patterning by Sonic hedgehog and its downstream signal response genes.

PubMed

Borycki, A G; Mendham, L; Emerson, C P

1998-02-01

In the avian embryo, previous work has demonstrated that the notochord provides inductive signals to activate myoD and pax1 regulatory genes, which are expressed in the dorsal and ventral somite cells that give rise to myotomal and sclerotomal lineages. Here, we present bead implantation and antisense inhibition experiments that show that Sonic hedgehog is both a sufficient and essential notochord signal molecule for myoD and pax1 activation in somites. Furthermore, we show that genes of the Sonic hedgehog signal response pathway, specifically patched, the Sonic hedgehog receptor, and gli and gli2/4, zinc-finger transcription factors, are activated in coordination with somite formation, establishing that Sonic hedgehog response genes play a regulatory role in coordinating the response of somites to the constitutive notochord Sonic hedgehog signal. Furthermore, the expression of patched, gli and gli2/4 is differentially patterned in the somite, providing mechanisms for differentially transducing the Sonic hedgehog signal to the myotomal and sclerotomal lineages. Finally, we show that the activation of gli2/4 is controlled by the process of somite formation and signals from the surface ectoderm, whereas upregulation of patched and activation of gli is controlled by the process of somite formation and a Sonic hedgehog signal. The Sonic hedgehog signal response genes, therefore, have important functions in regulating the initiation of the Sonic hedgehog response in newly forming somites and in regulating the patterned expression of myoD and pax1 in the myotomal and sclerotomal lineages following somite formation.

Genetic differentiation and phylogeographical structure of the Brachionus calyciflorus complex in eastern China.

PubMed

Xiang, Xian-Ling; Xi, Yi-Long; Wen, Xin-Li; Zhang, Gen; Wang, Jin-Xia; Hu, Ke

2011-07-01

Spatio-temporal patterns and processes of genetic differentiation in passively dispersing zooplankton are drawing much attention from both ecologists and evolutionary biologists. Two opposite phylogeographical scenarios have already been demonstrated in rotifers, which consist of high levels of genetic differentiation among populations even on small geographical scales on the one hand and the traditionally known cosmopolitanism that is associated with high levels of gene flow and long-distance dispersal via diapausing stages on the other hand. Here, we analysed the population genetic structure and the phylogeography of the Brachionus calyciflorus species complex in eastern China. By screening a total of 318 individuals from ten locations along a 2320-km gradient and analysing samples from two growing seasons, we aimed at focusing on both small- and large-scale patterns. We identified eight cryptic species and verified species status of two of these by sexual reproduction tests. Samples in summer and winter yielded different cryptic species. The distribution patterns of these genetically distinct cryptic species were diverse across eastern China, from full cosmopolitanism to local endemism. The two most abundant cryptic species BcWIII and BcSW showed a pattern of strong genetic differentiation among populations and no significant isolation by distance. Long-distance colonization, secondary contact and recent range expansion are probably responsible for the indistinct pattern of isolation by distance. Our results suggest that geographical distance is more important than temporal segregation across seasons in explaining population differentiation and the occurrence of cryptic species. We explain the current phylogeographical structure in the B. calyciflorus species complex by a combination of recent population expansion, restricted gene flow, priority effects and long-distance colonization. © 2011 Blackwell Publishing Ltd.

The Small-RNA Profiles of Almond (Prunus dulcis Mill.) Reproductive Tissues in Response to Cold Stress.

PubMed

Karimi, Marzieh; Ghazanfari, Farahnaz; Fadaei, Adeleh; Ahmadi, Laleh; Shiran, Behrouz; Rabei, Mohammad; Fallahi, Hossein

2016-01-01

Spring frost is an important environmental stress that threatens the production of Prunus trees. However, little information is available regarding molecular response of these plants to the frost stress. Using high throughput sequencing, this study was conducted to identify differentially expressed miRNAs, both the conserved and the non-conserved ones, in the reproductive tissues of almond tolerant H genotype under cold stress. Analysis of 50 to 58 million raw reads led to identification of 174 unique conserved and 59 novel microRNAs (miRNAs). Differential expression pattern analysis showed that 50 miRNA families were expressed differentially in one or both of almond reproductive tissues (anther and ovary). Out of these 50 miRNA families, 12 and 15 displayed up-regulation and down-regulation, respectively. The distribution of conserved miRNA families indicated that miR482f harbor the highest number of members. Confirmation of miRNAs expression patterns by quantitative real- time PCR (qPCR) was performed in cold tolerant (H genotype) alongside a sensitive variety (Sh12 genotype). Our analysis revealed differential expression for 9 miRNAs in anther and 3 miRNAs in ovary between these two varieties. Target prediction of miRNAs followed by differential expression analysis resulted in identification of 83 target genes, mostly transcription factors. This study comprehensively catalogued expressed miRNAs under different temperatures in two reproductive tissues (anther and ovary). Results of current study and the previous RNA-seq study, which was conducted in the same tissues by our group, provide a unique opportunity to understand the molecular basis of responses of almond to cold stress. The results can also enhance the possibility for gene manipulation to develop cold tolerant plants.

The Small-RNA Profiles of Almond (Prunus dulcis Mill.) Reproductive Tissues in Response to Cold Stress

PubMed Central

Shiran, Behrouz; Rabei, Mohammad; Fallahi, Hossein

2016-01-01

Spring frost is an important environmental stress that threatens the production of Prunus trees. However, little information is available regarding molecular response of these plants to the frost stress. Using high throughput sequencing, this study was conducted to identify differentially expressed miRNAs, both the conserved and the non-conserved ones, in the reproductive tissues of almond tolerant H genotype under cold stress. Analysis of 50 to 58 million raw reads led to identification of 174 unique conserved and 59 novel microRNAs (miRNAs). Differential expression pattern analysis showed that 50 miRNA families were expressed differentially in one or both of almond reproductive tissues (anther and ovary). Out of these 50 miRNA families, 12 and 15 displayed up-regulation and down-regulation, respectively. The distribution of conserved miRNA families indicated that miR482f harbor the highest number of members. Confirmation of miRNAs expression patterns by quantitative real- time PCR (qPCR) was performed in cold tolerant (H genotype) alongside a sensitive variety (Sh12 genotype). Our analysis revealed differential expression for 9 miRNAs in anther and 3 miRNAs in ovary between these two varieties. Target prediction of miRNAs followed by differential expression analysis resulted in identification of 83 target genes, mostly transcription factors. This study comprehensively catalogued expressed miRNAs under different temperatures in two reproductive tissues (anther and ovary). Results of current study and the previous RNA-seq study, which was conducted in the same tissues by our group, provide a unique opportunity to understand the molecular basis of responses of almond to cold stress. The results can also enhance the possibility for gene manipulation to develop cold tolerant plants. PMID:27253370

Genome-wide identification of heat stress-responsive small RNAs in tall fescue (Festuca arundinacea) by high-throughput sequencing.

PubMed

Li, Huiying; Hu, Tao; Amombo, Erick; Fu, Jinmin

2017-06-01

MicroRNAs (miRNAs) play vital roles in the adaptive response of plants to various abiotic and biotic stresses. Tall fescue (Festuca arundinacea Schreb.) is a major cool-season forage and turf grass species which is severely influenced by heat stress. To unravel possible heat stress-responsive miRNAs, high-throughput sequencing was employed for heat-tolerant PI578718 and heat-sensitive PI234881 genotypes growing in presence and absence of heat stress (40°C for 36h). By searching against the miRBase database, among 1421 reference monocotyledon miRNAs, more than 850 were identified in all samples. Among these miRNAs, 1.46% and 2.29% were differentially expressed in PI234881 and PI578718 under heat stress, respectively, and most of them were down-regulated. In addition, a total of 170 novel miRNAs belonging to 145 miRNA families were identified. Furthermore, putative targets of differentially expressed miRNAs were predicted. The regulation of selected miRNAs by heat stress was revalidated through quantitative reverse transcription PCR (qRT-PCR) analysis. Most of these miRNAs shared similar expression patterns; however, some showed distinct expression patterns under heat stress, with their putative targets displaying different transcription levels. This is the first genome-wide miRNA identification in tall fescue. miRNAs specific to PI578718, or those that exhibited differential expression profiles between the two genotypes under high temperature, were probably associated with the variation in thermotolerance of tall fescue. The differentially expressed miRNAs between these two tall fescue genotypes and their putative targeted genes will provide essential information for further study on miRNAs mediating heat response and facilitate to improve turf grass breeding. Copyright © 2017. Published by Elsevier GmbH.

Neural Correlates of Sexual Orientation in Heterosexual, Bisexual, and Homosexual Men

PubMed Central

Safron, Adam; Sylva, David; Klimaj, Victoria; Rosenthal, A. M.; Li, Meng; Walter, Martin; Bailey, J. Michael

2017-01-01

Studies of subjective and genital sexual arousal in monosexual (i.e. heterosexual and homosexual) men have repeatedly found that erotic stimuli depicting men’s preferred sex produce strong responses, whereas erotic stimuli depicting the other sex produce much weaker responses. Inconsistent results have previously been obtained in bisexual men, who have sometimes demonstrated distinctly bisexual responses, but other times demonstrated patterns more similar to those observed in monosexual men. We used fMRI to investigate neural correlates of responses to erotic pictures and videos in heterosexual, bisexual, and homosexual men, ages 25–50. Sixty participants were included in video analyses, and 62 were included in picture analyses. We focused on the ventral striatum (VS), due to its association with incentive motivation. Patterns were consistent with sexual orientation, with heterosexual and homosexual men showing female-favoring and male-favoring responses, respectively. Bisexual men tended to show less differentiation between male and female stimuli. Consistent patterns were observed in the whole brain, including the VS, and also in additional regions such as occipitotemporal, anterior cingulate, and orbitofrontal cortices. This study extends previous findings of gender-specific neural responses in monosexual men, and provides initial evidence for distinct brain activity patterns in bisexual men. PMID:28145518

Neural Correlates of Sexual Orientation in Heterosexual, Bisexual, and Homosexual Men.

PubMed

Safron, Adam; Sylva, David; Klimaj, Victoria; Rosenthal, A M; Li, Meng; Walter, Martin; Bailey, J Michael

2017-02-01

Studies of subjective and genital sexual arousal in monosexual (i.e. heterosexual and homosexual) men have repeatedly found that erotic stimuli depicting men's preferred sex produce strong responses, whereas erotic stimuli depicting the other sex produce much weaker responses. Inconsistent results have previously been obtained in bisexual men, who have sometimes demonstrated distinctly bisexual responses, but other times demonstrated patterns more similar to those observed in monosexual men. We used fMRI to investigate neural correlates of responses to erotic pictures and videos in heterosexual, bisexual, and homosexual men, ages 25-50. Sixty participants were included in video analyses, and 62 were included in picture analyses. We focused on the ventral striatum (VS), due to its association with incentive motivation. Patterns were consistent with sexual orientation, with heterosexual and homosexual men showing female-favoring and male-favoring responses, respectively. Bisexual men tended to show less differentiation between male and female stimuli. Consistent patterns were observed in the whole brain, including the VS, and also in additional regions such as occipitotemporal, anterior cingulate, and orbitofrontal cortices. This study extends previous findings of gender-specific neural responses in monosexual men, and provides initial evidence for distinct brain activity patterns in bisexual men.

Cardiovascular, electrodermal, and respiratory response patterns to fear- and sadness-inducing films.

PubMed

Kreibig, Sylvia D; Wilhelm, Frank H; Roth, Walton T; Gross, James J

2007-09-01

Responses to fear- and sadness-inducing films were assessed using a broad range of cardiovascular (heart rate, T-wave amplitude, low- and high-frequency heart rate variability, stroke volume, preejection period, left-ventricular ejection time, Heather index, blood pressure, pulse amplitude and transit time, and finger temperature), electrodermal (level, response rate, and response amplitude), and respiratory (rate, tidal volume and its variability, inspiratory flow rate, duty cycle, and end-tidal pCO(2)) measures. Subjective emotional experience and facial behavior (Corrugator Supercilii and Zygomaticus Major EMG) served as control measures. Results indicated robust differential physiological response patterns for fear, sadness, and neutral (mean classification accuracy 85%). Findings are discussed in terms of the fight-flight and conservation-withdrawal responses and possible limitations of a valence-arousal categorization of emotion in affective space.

Temporal and spatial expression patterns of Hedgehog receptors in the developing inner and middle ear.

PubMed

Shin, Jeong-Oh; Ankamreddy, Harinarayana; Jakka, Naga Mahesh; Lee, Seokwon; Kim, Un-Kyung; Bok, Jinwoong

2017-01-01

The mammalian inner ear is a complex organ responsible for balance and hearing. Sonic hedgehog (Shh), a member of the Hedgehog (Hh) family of secreted proteins, has been shown to play important roles in several aspects of inner ear development, including dorsoventral axial specification, cochlear elongation, tonotopic patterning, and hair cell differentiation. Hh proteins initiate a downstream signaling cascade by binding to the Patched 1 (Ptch1) receptor. Recent studies have revealed that other types of co-receptors can also mediate Hh signaling, including growth arrest-specific 1 (Gas1), cell-adhesion molecules-related/down-regulated by oncogenes (Cdon), and biregional Cdon binding protein (Boc). However, little is known about the role of these Hh co-receptors in inner ear development. In this study, we examined the expression patterns of Gas1, Cdon, and Boc, as well as that of Ptch1, in the developing mouse inner ear from otocyst (embryonic day (E) 9.5) until birth and in the developing middle ear at E15.5. Ptch1, a readout of Hh signaling, was expressed in a graded pattern in response to Shh signaling throughout development. Expression patterns of Gas1, Cdon, and Boc differed from that of Ptch1, and each Hh co-receptor was expressed in specific cells and domains in the developing inner and middle ear. These unique and differential expression patterns of Hh co-receptors suggest their roles in mediating various time- and space-specific functions of Shh during ear development.

Psychophysiological Outcome of Behavioral and Pharmacological Treatments of Agoraphobia.

ERIC Educational Resources Information Center

Michelson, Larry; Mavissakalian, Matig

1985-01-01

Examined relative and combined effectiveness of behavior therapy and pharmacotherapy in 62 severe, chronic agoraphobics. Identified differential temporal response and treatment patterns across psychophysiological domains. Synchrony/desynchrony phenomena yielded significant findings with regard to process and clinical outcome status. Exploratory…

Sex-based differences in gene expression in hippocampus following postnatal lead exposure

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

Schneider, J.S., E-mail: jay.schneider@jefferson.edu; Anderson, D.W.; Sonnenahalli, H.

The influence of sex as an effect modifier of childhood lead poisoning has received little systematic attention. Considering the paucity of information available concerning the interactive effects of lead and sex on the brain, the current study examined the interactive effects of lead and sex on gene expression patterns in the hippocampus, a structure involved in learning and memory. Male or female rats were fed either 1500 ppm lead-containing chow or control chow for 30 days beginning at weaning.Blood lead levels were 26.7 {+-} 2.1 {mu}g/dl and 27.1 {+-} 1.7 {mu}g/dl for females and males, respectively. The expression of 175more » unique genes was differentially regulated between control male and female rats. A total of 167 unique genes were differentially expressed in response to lead in either males or females. Lead exposure had a significant effect without a significant difference between male and female responses in 77 of these genes. In another set of 71 genes, there were significant differences in male vs. female response. A third set of 30 genes was differentially expressed in opposite directions in males vs. females, with the majority of genes expressed at a lower level in females than in males. Highly differentially expressed genes in males and females following lead exposure were associated with diverse biological pathways and functions. These results show that a brief exposure to lead produced significant changes in expression of a variety of genes in the hippocampus and that the response of the brain to a given lead exposure may vary depending on sex. - Highlights: > Postnatal lead exposure has a significant effect on hippocampal gene expression patterns. > At least one set of genes was affected in opposite directions in males and females. > Differentially expressed genes were associated with diverse biological pathways.« less

Control entropy identifies differential changes in complexity of walking and running gait patterns with increasing speed in highly trained runners

NASA Astrophysics Data System (ADS)

McGregor, Stephen J.; Busa, Michael A.; Skufca, Joseph; Yaggie, James A.; Bollt, Erik M.

2009-06-01

Regularity statistics have been previously applied to walking gait measures in the hope of gaining insight into the complexity of gait under different conditions and in different populations. Traditional regularity statistics are subject to the requirement of stationarity, a limitation for examining changes in complexity under dynamic conditions such as exhaustive exercise. Using a novel measure, control entropy (CE), applied to triaxial continuous accelerometry, we report changes in complexity of walking and running during increasing speeds up to exhaustion in highly trained runners. We further apply Karhunen-Loeve analysis in a new and novel way to the patterns of CE responses in each of the three axes to identify dominant modes of CE responses in the vertical, mediolateral, and anterior/posterior planes. The differential CE responses observed between the different axes in this select population provide insight into the constraints of walking and running in those who may have optimized locomotion. Future comparisons between athletes, healthy untrained, and clinical populations using this approach may help elucidate differences between optimized and diseased locomotor control.

Neural mechanisms of mismatch negativity dysfunction in schizophrenia.

PubMed

Lee, M; Sehatpour, P; Hoptman, M J; Lakatos, P; Dias, E C; Kantrowitz, J T; Martinez, A M; Javitt, D C

2017-11-01

Schizophrenia is associated with cognitive deficits that reflect impaired cortical information processing. Mismatch negativity (MMN) indexes pre-attentive information processing dysfunction at the level of primary auditory cortex. This study investigates mechanisms underlying MMN impairments in schizophrenia using event-related potential, event-related spectral decomposition (ERSP) and resting state functional connectivity (rsfcMRI) approaches. For this study, MMN data to frequency, intensity and duration-deviants were analyzed from 69 schizophrenia patients and 38 healthy controls. rsfcMRI was obtained from a subsample of 38 patients and 23 controls. As expected, schizophrenia patients showed highly significant, large effect size (P=0.0004, d=1.0) deficits in MMN generation across deviant types. In ERSP analyses, responses to deviants occurred primarily the theta (4-7 Hz) frequency range consistent with distributed corticocortical processing, whereas responses to standards occurred primarily in alpha (8-12 Hz) range consistent with known frequencies of thalamocortical activation. Independent deficits in schizophrenia were observed in both the theta response to deviants (P=0.021) and the alpha-response to standards (P=0.003). At the single-trial level, differential patterns of response were observed for frequency vs duration/intensity deviants, along with At the network level, MMN deficits engaged canonical somatomotor, ventral attention and default networks, with a differential pattern of engagement across deviant types (P<0.0001). Findings indicate that deficits in thalamocortical, as well as corticocortical, connectivity contribute to auditory dysfunction in schizophrenia. In addition, differences in ERSP and rsfcMRI profiles across deviant types suggest potential differential engagement of underlying generator mechanisms.

Functional screen reveals essential roles of miR-27a/24 in differentiation of embryonic stem cells

PubMed Central

Ma, Yanni; Yao, Nan; Liu, Guang; Dong, Lei; Liu, Yufang; Zhang, Meili; Wang, Fang; Wang, Bin; Wei, Xueju; Dong, He; Wang, Lanlan; Ji, Shaowei; Zhang, Junwu; Wang, Yangming; Huang, Yue; Yu, Jia

2015-01-01

MicroRNAs play important roles in controlling the embryonic stem cell (ESC) state. Although much is known about microRNAs maintaining ESC state, microRNAs that are responsible for promoting ESC differentiation are less reported. Here, by screening 40 microRNAs pre-selected by their expression patterns and predicted targets in Dgcr8-null ESCs, we identify 14 novel differentiation-associated microRNAs. Among them, miR-27a and miR-24, restrained by c-Myc in ESC, exert their roles of silencing self-renewal through directly targeting several important pluripotency-associated factors, such as Oct4, Foxo1 and Smads. CRISPR/Cas9-mediated knockout of all miR-27/24 in ESCs leads to serious deficiency in ESC differentiation in vitro and in vivo. Moreover, depleting of them in mouse embryonic fibroblasts can evidently promote somatic cell reprogramming. Altogether, our findings uncover the essential role of miR-27 and miR-24 in ESC differentiation and also demonstrate novel microRNAs responsible for ESC differentiation. PMID:25519956

Modulation of Dendritic Cell Activation and Subsequent Th1 Cell Polarization by Lidocaine

PubMed Central

Chung, Yeonseok

2015-01-01

Dendritic cells play an essential role in bridging innate and adaptive immunity by recognizing cellular stress including pathogen- and damage-associated molecular patterns and by shaping the types of antigen-specific T cell immunity. Although lidocaine is widely used in clinical settings that trigger cellular stress, it remains unclear whether such treatment impacts the activation of innate immune cells and subsequent differentiation of T cells. Here we showed that lidocaine inhibited the production of IL–6, TNFα and IL–12 from dendritic cells in response to toll-like receptor ligands including lipopolysaccharide, poly(I:C) and R837 in a dose-dependent manner. Notably, the differentiation of Th1 cells was significantly suppressed by the addition of lidocaine while the same treatment had little effect on the differentiation of Th17, Th2 and regulatory T cells in vitro. Moreover, lidocaine suppressed the ovalbumin-specific Th1 cell responses in vivo induced by the adoptive transfer of ovalbumin-pulsed dendritic cells. These results demonstrate that lidocaine inhibits the activation of dendritic cells in response to toll-like receptor signals and subsequently suppresses the differentiation of Th1 cell responses. PMID:26445366

Unravelling a biogeographical knot: origin of the 'leapfrog' distribution pattern of Australo-Papuan sooty owls (Strigiformes) and logrunners (Passeriformes).

PubMed

Norman, J A; Christidis, L; Joseph, L; Slikas, B; Alpers, D

2002-10-22

Molecular analysis of two Australo-Papuan rainforest birds exhibiting correlated 'leapfrog' patterns were used to elucidate the evolutionary origin of this unusual pattern of geographical differentiation. In both sooty owls (Tyto) and logrunners (Orthonyx), phenotypically similar populations occupy widely disjunct areas (central-eastern Australia and upland New Guinea) with a third, highly distinctive population, occurring between them in northeastern Queensland. Two mechanisms have been proposed to explain the origin of leapfrog patterns in avian distributions: recent shared ancestry of terminal populations and unequal rates or phenotypic change among populations. As the former should generate correlated patterns of phenotypic and genetic differentiation, we tested for a sister relationship between populations from New Guinea and central-eastern Australia using nuclear and mitochondrial DNA sequences. The resulting phylogenies not only refute recent ancestry as an explanation for the leapfrog pattern, but provide evidence of vastly different spatio-temporal histories for sooty owls and logrunners within the Australo-Papuan rainforests. This incongruence indicates that the evolutionary processes responsible for generating leapfrog patterns in these co-distributed taxa are complex, possibly involving a combination of selection and drift in sooty owls and convergence or retention of ancestral characteristics in logrunners.

Genetic Differentiation in Insular Lowland Rainforests: Insights from Historical Demographic Patterns in Philippine Birds

PubMed Central

Sánchez-González, Luis Antonio; Hosner, Peter A.; Moyle, Robert G.

2015-01-01

Phylogeographic studies of Philippine birds support that deep genetic structure occurs across continuous lowland forests within islands, despite the lack of obvious contemporary isolation mechanisms. To examine the pattern and tempo of diversification within Philippine island forests, and test if common mechanisms are responsible for observed differentiation, we focused on three co-distributed lowland bird taxa endemic to Greater Luzon and Greater Negros-Panay: Blue-headed Fantail (Rhipidura cyaniceps), White-browed Shama (Copsychus luzoniensis), and Lemon-throated Leaf-Warbler (Phylloscopus cebuensis). Each species has two described subspecies within Greater Luzon, and a single described subspecies on Greater Negros/Panay. Each of the three focal species showed a common geographic pattern of two monophyletic groups in Greater Luzon sister to a third monophyletic group found in Greater Negros-Panay, suggesting that common or similar biogeographic processes may have produced similar distributions. However, studied species displayed variable levels of mitochondrial DNA differentiation between clades, and genetic differentiation within Luzon was not necessarily concordant with described subspecies boundaries. Population genetic parameters for the three species suggested both rapid population growth from small numbers and geographic expansion across Luzon Island. Estimates of the timing of population expansion further supported that these events occurred asynchronously throughout the Pleistocene in the focal species, demanding particular explanations for differentiation, and support that co-distribution may be secondarily congruent. PMID:26312748

Genetic Differentiation in Insular Lowland Rainforests: Insights from Historical Demographic Patterns in Philippine Birds.

PubMed

Sánchez-González, Luis Antonio; Hosner, Peter A; Moyle, Robert G

2015-01-01

Phylogeographic studies of Philippine birds support that deep genetic structure occurs across continuous lowland forests within islands, despite the lack of obvious contemporary isolation mechanisms. To examine the pattern and tempo of diversification within Philippine island forests, and test if common mechanisms are responsible for observed differentiation, we focused on three co-distributed lowland bird taxa endemic to Greater Luzon and Greater Negros-Panay: Blue-headed Fantail (Rhipidura cyaniceps), White-browed Shama (Copsychus luzoniensis), and Lemon-throated Leaf-Warbler (Phylloscopus cebuensis). Each species has two described subspecies within Greater Luzon, and a single described subspecies on Greater Negros/Panay. Each of the three focal species showed a common geographic pattern of two monophyletic groups in Greater Luzon sister to a third monophyletic group found in Greater Negros-Panay, suggesting that common or similar biogeographic processes may have produced similar distributions. However, studied species displayed variable levels of mitochondrial DNA differentiation between clades, and genetic differentiation within Luzon was not necessarily concordant with described subspecies boundaries. Population genetic parameters for the three species suggested both rapid population growth from small numbers and geographic expansion across Luzon Island. Estimates of the timing of population expansion further supported that these events occurred asynchronously throughout the Pleistocene in the focal species, demanding particular explanations for differentiation, and support that co-distribution may be secondarily congruent.

Acute virus control mediated by licensed NK cells sets primary CD8+ T cell dependence on CD27 costimulation1,2,3

PubMed Central

Teoh, Jeffrey J.; Gamache, Awndre E.; Gillespie, Alyssa L.; Stadnisky, Michael D.; Yagita, Hideo; Bullock, Timothy N.J.; Brown, Michael G.

2016-01-01

Natural killer (NK) cells represent a critical first-line of immune defense against a bevy of viral pathogens, and infection can provoke them to mediate both supportive and suppressive effects on virus-specific adaptive immunity. In mice expressing MHC I Dk, a major MCMV resistance factor and self-ligand of the inhibitory Ly49G2 (G2) receptor, licensed G2+ NK cells provide essential host resistance against murine (M)CMV infection. Additionally G2+ NK cell responses to MCMV increase the rate and extent of dendritic cell (DC) recovery, as well as early priming of CD8+ T-cell effectors in response to MCMV. However, relatively little is known about the NK-cell effect on co-stimulatory ligand patterns displayed by DCs, or ensuing effector and memory T-cell responses. Here we found that CD27-dependent CD8+ T-cell priming and differentiation is shaped by the efficiency of NK responses to virus infection. Surprisingly, differences in specific NK responses to MCMV in Dk-disparate mice failed to distinguish early DC co-stimulatory patterns. Nonetheless, while CD27 deficiency did not impede licensed NK-mediated resistance, both CD70 and CD27 were required to efficiently prime and regulate effector CD8+ T-cell differentiation in response to MCMV, which eventually resulted in biased memory T-cell precursor formation in Dk mice. In contrast, CD8+ T-cells accrued more slowly in non-Dk mice, and eventually differentiated into terminal effector cells regardless of CD27 stimulation. Disparity in this requirement for CD27 signaling indicates that specific virus control mediated by NK cells can shape DC co-stimulatory signals needed to prime CD8+ T cells and eventual T-cell fate decisions. PMID:27798162

A stimulus-control account of dysregulated drug intake.

PubMed

Panlilio, Leigh V; Thorndike, Eric B; Schindler, Charles W

2009-05-01

Drug self-administration typically occurs in a regular temporal pattern, with a consistent pause following each injection. We have proposed that this patterning results from differential reinforcement of post-injection pausing. In this view, even when every response produces an injection, some injections are not reinforcing because they occur when the level of drug effect is already maximal; consequently, drug reinforcement occurs on an intermittent schedule, and the interoceptive drug effect functions as a cue, indicating when another injection will be reinforcing. Previously, we emulated this situation with rats by using food reinforcement; each response was recorded as delivering a "virtual" injection, and a visual cue tracked the virtual drug level to indicate availability of reinforcement. This emulation schedule produced response patterns strikingly similar to actual drug self-administration. In the present study, the emulation schedule was modified to determine whether reinforcement of pausing is sufficient to produce these patterns, or whether a cue is necessary. Without a cue, response patterns were irregular and virtual drug intake was escalated. These results suggest that a failure of interoceptive cues to control pausing might contribute to the dysregulated drug intake that is associated with addiction.

Differential expression of human lysyl hydroxylase genes, lysine hydroxylation, and cross-linking of type I collagen during osteoblastic differentiation in vitro

NASA Technical Reports Server (NTRS)

Uzawa, K.; Grzesik, W. J.; Nishiura, T.; Kuznetsov, S. A.; Robey, P. G.; Brenner, D. A.; Yamauchi, M.

1999-01-01

The pattern of lysyl hydroxylation in the nontriple helical domains of collagen is critical in determining the cross-linking pathways that are tissue specific. We hypothesized that the tissue specificity of type I collagen cross-linking is, in part, due to the differential expression of lysyl hydroxylase genes (Procollagen-lysine,2-oxyglutarate,5-dioxygenase 1, 2, and 3 [PLOD1, PLOD2, and PLOD3]). In this study, we have examined the expression patterns of these three genes during the course of in vitro differentiation of human osteoprogenitor cells (bone marrow stromal cells [BMSCs]) and normal skin fibroblasts (NSFs). In addition, using the medium and cell layer/matrix fractions in these cultures, lysine hydroxylation of type I collagen alpha chains and collagen cross-linking chemistries have been characterized. High levels of PLOD1 and PLOD3 genes were expressed in both BMSCs and NSFs, and the expression levels did not change in the course of differentiation. In contrast to the PLOD1 and PLOD3 genes, both cell types showed low PLOD2 gene expression in undifferentiated and early differentiated conditions. However, fully differentiated BMSCs, but not NSFs, exhibited a significantly elevated level (6-fold increase) of PLOD2 mRNA. This increase coincided with the onset of matrix mineralization and with the increase in lysyl hydroxylation in the nontriple helical domains of alpha chains of type I collagen molecule. Furthermore, the collagen cross-links that are derived from the nontriple helical hydroxylysine-aldehyde were found only in fully differentiated BMSC cultures. The data suggests that PLOD2 expression is associated with lysine hydroxylation in the nontriple helical domains of collagen and, thus, could be partially responsible for the tissue-specific collagen cross-linking pattern.

Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival.

PubMed

Nguyen, Chinh Bkrong; Alsøe, Lene; Lindvall, Jessica M; Sulheim, Dag; Fagermoen, Even; Winger, Anette; Kaarbø, Mari; Nilsen, Hilde; Wyller, Vegard Bruun

2017-05-11

Chronic fatigue syndrome (CFS) is a prevalent and disabling condition affecting adolescents. The pathophysiology is poorly understood, but immune alterations might be an important component. This study compared whole blood gene expression in adolescent CFS patients and healthy controls, and explored associations between gene expression and neuroendocrine markers, immune markers and clinical markers within the CFS group. CFS patients (12-18 years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project. A broad case definition of CFS was applied, requiring 3 months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Healthy controls having comparable distribution of gender and age were recruited from local schools. Whole blood samples were subjected to RNA sequencing. Immune markers were blood leukocyte counts, plasma cytokines, serum C-reactive protein and immunoglobulins. Neuroendocrine markers encompassed plasma and urine levels of catecholamines and cortisol, as well as heart rate variability indices. Clinical markers consisted of questionnaire scores for symptoms of post-exertional malaise, inflammation, fatigue, depression and trait anxiety, as well as activity recordings. A total of 29 CFS patients and 18 healthy controls were included. We identified 176 genes as differentially expressed in patients compared to controls, adjusting for age and gender factors. Gene set enrichment analyses suggested impairment of B cell differentiation and survival, as well as enhancement of innate antiviral responses and inflammation in the CFS group. A pattern of co-expression could be identified, and this pattern, as well as single gene transcripts, was significantly associated with indices of autonomic nervous activity, plasma cortisol, and blood monocyte and eosinophil counts. Also, an association with symptoms of post-exertional malaise was demonstrated. Adolescent CFS is characterized by differential gene expression pattern in whole blood suggestive of impaired B cell differentiation and survival, and enhanced innate antiviral responses and inflammation. This expression pattern is associated with neuroendocrine markers of altered HPA axis and autonomic nervous activity, and with symptoms of post-exertional malaise. Trial registration Clinical Trials NCT01040429.

Ethylene-responsive genes are differentially regulated during abscission, organ senescence and wounding in peach (Prunus persica).

PubMed

Ruperti, Benedetto; Cattivelli, Luigi; Pagni, Silvana; Ramina, Angelo

2002-03-01

Ethylene-responsive genes from peach (Prunus persica, L. Batsch) were isolated by differential screening of a cDNA library constructed from abscission zones in which cell separation had been evoked by treatment with the ethylene analogue propylene. DNA and deduced protein sequences of four selected clones, termed Prunus persica Abscission zone (PpAz), revealed homology to thaumatin-like proteins (PpAz8 and PpAz44), to proteins belonging to the PR4 class of pathogenesis-related (PR) proteins (PpAz89), and to fungal and plant beta-D-xylosidases (PpAz152). Expression analyses conducted on embrioctomized and CEPA-treated fruitlets as well as on fruit explants have shown that PpAz8, PpAz44 and PpAz89 are preferentially transcribed in the cells of the fruit abscission zone rather than in the non-zone tissues. The PpAz152 transcript showed a different accumulation pattern being consistently and promptly induced by wounding and only slightly stimulated by propylene. By contrast, a complex pattern of transcript accumulation was found for the four genes in response to the wounding of leaves and during organ development and senescence. Based on this evidence, the existence of multiple regulatory pathways underlying the differential expression of the four PpAz genes in the different tissues and physiological processes is hypothesized.

Multi-voxel Patterns Reveal Functionally Differentiated Networks Underlying Auditory Feedback Processing of Speech

PubMed Central

Zheng, Zane Z.; Vicente-Grabovetsky, Alejandro; MacDonald, Ewen N.; Munhall, Kevin G.; Cusack, Rhodri; Johnsrude, Ingrid S.

2013-01-01

The everyday act of speaking involves the complex processes of speech motor control. An important component of control is monitoring, detection and processing of errors when auditory feedback does not correspond to the intended motor gesture. Here we show, using fMRI and converging operations within a multi-voxel pattern analysis framework, that this sensorimotor process is supported by functionally differentiated brain networks. During scanning, a real-time speech-tracking system was employed to deliver two acoustically different types of distorted auditory feedback or unaltered feedback while human participants were vocalizing monosyllabic words, and to present the same auditory stimuli while participants were passively listening. Whole-brain analysis of neural-pattern similarity revealed three functional networks that were differentially sensitive to distorted auditory feedback during vocalization, compared to during passive listening. One network of regions appears to encode an ‘error signal’ irrespective of acoustic features of the error: this network, including right angular gyrus, right supplementary motor area, and bilateral cerebellum, yielded consistent neural patterns across acoustically different, distorted feedback types, only during articulation (not during passive listening). In contrast, a fronto-temporal network appears sensitive to the speech features of auditory stimuli during passive listening; this preference for speech features was diminished when the same stimuli were presented as auditory concomitants of vocalization. A third network, showing a distinct functional pattern from the other two, appears to capture aspects of both neural response profiles. Taken together, our findings suggest that auditory feedback processing during speech motor control may rely on multiple, interactive, functionally differentiated neural systems. PMID:23467350

Influence of contingency awareness on neural, electrodermal and evaluative responses during fear conditioning

PubMed Central

Merz, Christian J.; Klucken, Tim; Schweckendiek, Jan; Vaitl, Dieter; Wolf, Oliver T.; Stark, Rudolf

2011-01-01

In an fMRI study, effects of contingency awareness on conditioned responses were assessed in three groups comprising 118 subjects. A differential fear-conditioning paradigm with visual conditioned stimuli, an electrical unconditioned stimulus and two distractors was applied. The instructed aware group was informed about the contingencies, whereas the distractors prevented contingency detection in the unaware group. The third group (learned aware) was not informed about the contingencies, but learned them despite the distractors. Main effects of contingency awareness on conditioned responses emerged in several brain structures. Post hoc tests revealed differential dorsal anterior cingulate, insula and ventral striatum responses in aware conditioning only, whereas the amygdala was activated independent of contingency awareness. Differential responses of the hippocampus were specifically observed in learned aware subjects, indicating a role in the development of contingency awareness. The orbitofrontal cortex showed varying response patterns: lateral structures showed higher responses in instructed aware than unaware subjects, the opposite was true for medial parts. Conditioned subjective and electrodermal responses emerged only in the two aware groups. These results confirm the independence of conditioned amygdala responses from contingency awareness and indicate specific neural circuits for different aspects of fear acquisition in unaware, learned aware and instructed aware subjects. PMID:20693389

Response Rates to Anticonvulsant Trials in Patients with Triphasic-Wave EEG Patterns of Uncertain Significance.

PubMed

O'Rourke, Deirdre; Chen, Patrick M; Gaspard, Nicolas; Foreman, Brandon; McClain, Lauren; Karakis, Ioannis; Mahulikar, Advait; Westover, M Brandon

2016-04-01

Generalized triphasic waves (TPWs) occur in both metabolic encephalopathies and non-convulsive status epilepticus (NCSE). Empiric trials of benzodiazepines (BZDs) or non-sedating AED (NSAEDs) are commonly used to differentiate the two, but the utility of such trials is debated. The goal of this study was to assess response rates of such trials and investigate whether metabolic profile differences affect the likelihood of a response. Three institutions within the Critical Care EEG Monitoring Research Consortium retrospectively identified patients with unexplained encephalopathy and TPWs who had undergone a trial of BZD and/or NSAEDs to differentiate between ictal and non-ictal patterns. We assessed responder rates and compared metabolic profiles of responders and non-responders. Response was defined as resolution of the EEG pattern and either unequivocal improvement in encephalopathy or appearance of previously absent normal EEG patterns, and further categorized as immediate (within <2 h of trial initiation) or delayed (>2 h from trial initiation). We identified 64 patients with TPWs who had an empiric trial of BZD and/or NSAED. Most patients (71.9%) were admitted with metabolic derangements and/or infection. Positive clinical responses occurred in 10/53 (18.9%) treated with BZDs. Responses to NSAEDs occurred in 19/45 (42.2%), being immediate in 6.7%, delayed but definite in 20.0%, and delayed but equivocal in 15.6%. Overall, 22/64 (34.4%) showed a definite response to either BZDs or NSAEDs, and 7/64 (10.9%) showed a possible response. Metabolic differences of responders versus non-responders were statistically insignificant, except that the 48-h low value of albumin in the BZD responder group was lower than in the non-responder group. Similar metabolic profiles in patients with encephalopathy and TPWs between responders and non-responders to anticonvulsants suggest that predicting responders a priori is difficult. The high responder rate suggests that empiric trials of anticonvulsants indeed provide useful clinical information. The more than twofold higher response rate to NSAEDs suggests that this strategy may be preferable to BZDs. Further prospective investigation is warranted.

Response Rates to Anticonvulsant Trials in Patients with Triphasic-Wave EEG Patterns of Uncertain Significance

PubMed Central

O’Rourke, Deirdre; Chen, Patrick M.; Gaspard, Nicolas; Foreman, Brandon; McClain, Lauren; Karakis, Ioannis; Mahulikar, Advait

2016-01-01

Background Generalized triphasic waves (TPWs) occur in both metabolic encephalopathies and non-convulsive status epilepticus (NCSE). Empiric trials of benzodiazepines (BZDs) or non-sedating AED (NSAEDs) are commonly used to differentiate the two, but the utility of such trials is debated. The goal of this study was to assess response rates of such trials and investigate whether metabolic profile differences affect the likelihood of a response. Methods Three institutions within the Critical Care EEG Monitoring Research Consortium retrospectively identified patients with unexplained encephalopathy and TPWs who had undergone a trial of BZD and/or NSAEDs to differentiate between ictal and non-ictal patterns. We assessed responder rates and compared metabolic profiles of responders and non-responders. Response was defined as resolution of the EEG pattern and either unequivocal improvement in encephalopathy or appearance of previously absent normal EEG patterns, and further categorized as immediate (within <2 h of trial initiation) or delayed (>2 h from trial initiation). Results We identified 64 patients with TPWs who had an empiric trial of BZD and/or NSAED. Most patients (71.9 %) were admitted with metabolic derangements and/or infection. Positive clinical responses occurred in 10/53 (18.9 %) treated with BZDs. Responses to NSAEDs occurred in 19/45 (42.2 %), being immediate in 6.7 %, delayed but definite in 20.0 %, and delayed but equivocal in 15.6 %. Overall, 22/64 (34.4 %) showed a definite response to either BZDs or NSAEDs, and 7/64 (10.9 %) showed a possible response. Metabolic differences of responders versus non-responders were statistically insignificant, except that the 48-h low value of albumin in the BZD responder group was lower than in the non-responder group. Conclusions Similar metabolic profiles in patients with encephalopathy and TPWs between responders and non-responders to anticonvulsants suggest that predicting responders a priori is difficult. The high responder rate suggests that empiric trials of anticonvulsants indeed provide useful clinical information. The more than twofold higher response rate to NSAEDs suggests that this strategy may be preferable to BZDs. Further prospective investigation is warranted. PMID:26013921

The heart-break of social rejection versus the brain wave of social acceptance

PubMed Central

van der Molen, Maurits W.; Sahibdin, Priya P.; Franken, Ingmar H. A.

2014-01-01

The effect of social rejection on cardiac and brain responses was examined in a study in which participants had to decide on the basis of pictures of virtual peers whether these peers would like them or not. Physiological and behavioral responses to expected and unexpected acceptance and rejection were compared. It was found that participants expected that about 50% of the virtual judges gave them a positive judgment. Cardiac deceleration was strongest for unexpected social rejection. In contrast, the brain response was strongest to expected acceptance and was characterized by a positive deflection peaking around 325 ms following stimulus onset and the observed difference was maximal at fronto-central positions. The cardiac and electro-cortical responses were not related. It is hypothesized that these differential response patterns might be related to earlier described differential involvement of the dorsal and ventral portion of the anterior cingulate cortex. PMID:23887821

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

PubMed

Kafkas, Alexandros; Montaldi, Daniela

2011-10-01

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

Nanoscale definition of substrate materials to direct human adult stem cells towards tissue specific populations.

PubMed

Curran, Judith M; Chen, Rui; Stokes, Robert; Irvine, Eleanor; Graham, Duncan; Gubbins, Earl; Delaney, Deany; Amro, Nabil; Sanedrin, Raymond; Jamil, Haris; Hunt, John A

2010-03-01

The development of homogenously nano-patterned chemically modified surfaces that can be used to initiate a cellular response, particularly stem cell differentiation, in a highly controlled manner without the need for exogenous biological factors has never been reported, due to that fact that precisely defined and reproducible systems have not been available that can be used to study cell/material interactions and unlock the potential of a material driven cell response. Until now material driven stem cell (furthermore any cell) responses have been variable due to the limitations in definition and reproducibility of the underlying substrate and the lack of true homogeneity of modifications that can dictate a cellular response at a sub-micron level that can effectively control initial cell interactions of all cells that contact the surface. Here we report the successful design and use of homogenously molecularly nanopatterned surfaces to control initial stem cell adhesion and hence function. The highly specified nano-patterned arrays were compared directly to silane modified bulk coated substrates that have previously been proven to initiate mesenchymal stem cell (MSC) differentiation in a heterogenous manner, the aim of this study was to prove the efficiency of these previously observed cell responses could be enhanced by the incorporation of nano-patterns. Nano-patterned surfaces were prepared by Dip Pen Nanolithography (DPN) to produce arrays of 70 nm sized dots separated by defined spacings of 140, 280 and 1000 nm with terminal functionalities of carboxyl, amino, methyl and hydroxyl and used to control cell growth. These nanopatterned surfaces exhibited unprecedented control of initial cell interactions and will change the capabilities for stem cell definition in vitro and then cell based medical therapies. In addition to highlighting the ability of the materials to control stem cell functionality on an unprecedented scale this research also introduces the successful scale-up of DPN and the novel chemistries and systems to facilitate the production of homogeneously patterned substrates (5 mm2) that are applicable for use in in vitro cell conditions over prolonged periods for complete control of material driven cell responses.

Differentiating Human Multipotent Mesenchymal Stromal Cells Regulate microRNAs: Prediction of microRNA Regulation by PDGF During Osteogenesis

PubMed Central

Goff, Loyal A.; Boucher, Shayne; Ricupero, Christopher L.; Fenstermacher, Sara; Swerdel, Mavis; Chase, Lucas; Adams, Christopher; Chesnut, Jonathan; Lakshmipathy, Uma; Hart, Ronald P.

2009-01-01

Objective Human multipotent mesenchymal stromal cells (MSC) have the potential to differentiate into multiple cell types, although little is known about factors that control their fate. Differentiation-specific microRNAs may play a key role in stem cell self renewal and differentiation. We propose that specific intracellular signalling pathways modulate gene expression during differentiation by regulating microRNA expression. Methods Illumina mRNA and NCode microRNA expression analyses were performed on MSC and their differentiated progeny. A combination of bioinformatic prediction and pathway inhibition was used to identify microRNAs associated with PDGF signalling. Results The pattern of microRNA expression in MSC is distinct from that in pluripotent stem cells such as human embryonic stem cells. Specific populations of microRNAs are regulated in MSC during differentiation targeted towards specific cell types. Complementary mRNA expression analysis increases the pool of markers characteristic of MSC or differentiated progeny. To identify microRNA expression patterns affected by signalling pathways, we examined the PDGF pathway found to be regulated during osteogenesis by microarray studies. A set of microRNAs bioinformatically predicted to respond to PDGF signalling was experimentally confirmed by direct PDGF inhibition. Conclusion Our results demonstrate that a subset of microRNAs regulated during osteogenic differentiation of MSCs is responsive to perturbation of the PDGF pathway. This approach not only identifies characteristic classes of differentiation-specific mRNAs and microRNAs, but begins to link regulated molecules with specific cellular pathways. PMID:18657893

Computer based imaging and analysis of root gravitropism

NASA Technical Reports Server (NTRS)

Evans, M. L.; Ishikawa, H.

1997-01-01

Two key issues in studies of the nature of the gravitropic response in roots have been the determination of the precise pattern of differential elongation responsible for downward bending and the identification of the cells that show the initial motor response. The main approach for examining patterns of differential growth during root gravitropic curvature has been to apply markers to the root surface and photograph the root at regular intervals during gravitropic curvature. Although these studies have provided valuable information on the characteristics of the gravitropic motor response in roots, their labor intensive nature limits sample size and discourages both high frequency of sampling and depth of analysis of surface expansion data. In this brief review we describe the development of computer-based video analysis systems for automated measurement of root growth and shape change and discuss some key features of the root gravitropic response that have been revealed using this methodology. We summarize the capabilities of several new pieces of software designed to measure growth and shape changes in graviresponding roots and describe recent progress in developing analysis systems for studying the small, but experimentally popular, primary roots of Arabidopsis. A key finding revealed by such studies is that the initial gravitropic response of roots of maize and Arabidopsis occurs in the distal elongation zone (DEZ) near the root apical meristem, not in the main elongation zone. Another finding is that the initiation of rapid elongation in the DEZ following gravistimulation appears to be related to rapid membrane potential changes in this region of the root. These observations have provided the incentive for ongoing studies examining possible links between potential growth modifying factors (auxin, calcium, protons) and gravistimulated changes in membrane potential and growth patterns in the DEZ.

Varying Inundation Regimes Differentially Affect Natural and Sand-Amended Marsh Sediments

EPA Science Inventory

Climate change is altering sea-level rise rates and precipitation patterns worldwide. Coastal wetlands are vulnerable to these changes. System responses to stressors are important for resource managers and environmental stewards to understand in order to best manage them. Thin la...

Preliminary analysis of cold stress responsive proteins in Mesocestoides corti larvae.

PubMed

Canclini, Lucía; Esteves, Adriana

2007-07-01

Many parasites undergo sudden changes in environmental conditions at some stage during their life cycle. The molecular response to this variation is characterised by a rapid transcriptional activation of a specific set of genes coding for proteins generically known as stress proteins. They appear to be also involved in various biological processes including cell proliferation and differentiation. The platyhelminth parasite, Mesocestoides corti (Cestoda) presents important properties as a model organism. Under stress conditions, key molecules involved in metabolic pathways as well as in the growth and differentiation of the parasite can be identified. 2D protein expression profile of tetrathyridia of M. corti, submitted to nutritional starvation and cold stress is described, as well as the recovery pattern. A set of specifically expressed proteins was observed in each experimental condition. Quantitative and qualitative differences and stress recovery pattern are also reported. This work makes evident the high plasticity and resistance to extreme environmental conditions of these parasites at the molecular level.

Microarray Analysis Gene Expression Profiles in Laryngeal Muscle After Recurrent Laryngeal Nerve Injury.

PubMed

Bijangi-Vishehsaraei, Khadijeh; Blum, Kevin; Zhang, Hongji; Safa, Ahmad R; Halum, Stacey L

2016-03-01

The pathophysiology of recurrent laryngeal nerve (RLN) transection injury is rare in that it is characteristically followed by a high degree of spontaneous reinnervation, with reinnervation of the laryngeal adductor complex (AC) preceding that of the abducting posterior cricoarytenoid (PCA) muscle. Here, we aim to elucidate the differentially expressed myogenic factors following RLN injury that may be at least partially responsible for the spontaneous reinnervation. F344 male rats underwent RLN injury (n = 12) or sham surgery (n = 12). One week after RLN injury, larynges were harvested following euthanasia. The mRNA was extracted from PCA and AC muscles bilaterally, and microarray analysis was performed using a full rat genome array. Microarray analysis of denervated AC and PCA muscles demonstrated dramatic differences in gene expression profiles, with 205 individual probes that were differentially expressed between the denervated AC and PCA muscles and only 14 genes with similar expression patterns. The differential expression patterns of the AC and PCA suggest different mechanisms of reinnervation. The PCA showed the gene patterns of Wallerian degeneration, while the AC expressed the gene patterns of reinnervation by adjacent axonal sprouting. This finding may reveal important therapeutic targets applicable to RLN and other peripheral nerve injuries. © The Author(s) 2015.

Single grating x-ray imaging for dynamic biological systems

NASA Astrophysics Data System (ADS)

Morgan, Kaye S.; Paganin, David M.; Parsons, David W.; Donnelley, Martin; Yagi, Naoto; Uesugi, Kentaro; Suzuki, Yoshio; Takeuchi, Akihisa; Siu, Karen K. W.

2012-07-01

Biomedical studies are already benefiting from the excellent contrast offered by phase contrast x-ray imaging, but live imaging work presents several challenges. Living samples make it particularly difficult to achieve high resolution, sensitive phase contrast images, as exposures must be short and cannot be repeated. We therefore present a single-exposure, high-flux method of differential phase contrast imaging [1, 2, 3] in the context of imaging live airways for Cystic Fibrosis (CF) treatment assessment [4]. The CF study seeks to non-invasively observe the liquid lining the airways, which should increase in depth in response to effective treatments. Both high spatial resolution and sensitivity are required in order to track micron size changes in a liquid that is not easily differentiated from the tissue on which it lies. Our imaging method achieves these goals by using a single attenuation grating or grid as a reference pattern, and analyzing how the sample deforms the pattern to quantitatively retrieve the phase depth of the sample. The deformations are mapped at each pixel in the image using local cross-correlations comparing each 'sample and pattern' image with a reference 'pattern only' image taken before the sample is introduced. This produces a differential phase image, which may be integrated to give the sample phase depth.

Which limb is it? Responses to vibrotactile stimulation in early infancy.

PubMed

Somogyi, Eszter; Jacquey, Lisa; Heed, Tobias; Hoffmann, Matej; Lockman, Jeffrey J; Granjon, Lionel; Fagard, Jacqueline; O'Regan, J Kevin

2017-12-11

This study focuses on how the body schema develops during the first months of life, by investigating infants' motor responses to localized vibrotactile stimulation on their limbs. Vibrotactile stimulation was provided by small buzzers that were attached to the infants' four limbs one at a time. Four age groups were compared cross-sectionally (3-, 4-, 5-, and 6-month-olds). We show that before they actually reach for the buzzer, which, according to previous studies, occurs around 7-8 months of age, infants demonstrate emerging knowledge about their body's configuration by producing specific movement patterns associated with the stimulated body area. At 3 months, infants responded with an increase in general activity when the buzzer was placed on the body, independently of the vibrator's location. Differentiated topographical awareness of the body seemed to appear around 5 months, with specific responses resulting from stimulation of the hands emerging first, followed by the differentiation of movement patterns associated with the stimulation of the feet. Qualitative analyses revealed specific movement types reliably associated with each stimulated location by 6 months of age, possibly preparing infants' ability to actually reach for the vibrating target. We discuss this result in relation to newborns' ability to learn specific movement patterns through intersensory contingency. Statement of contribution what is already known on infants' sensorimotor knowledge about their own bodies 3-month-olds readily learn to produce specific limb movements to obtain a desired effect (movement of a mobile). infants detect temporal and spatial correspondences between events involving their own body and visual events. what the present study adds until 4-5 months of age, infants mostly produce general motor responses to localized touch. this is because in the present study, infants could not rely on immediate contingent feedback. we propose a cephalocaudal developmental trend of topographic differentiation of body areas. © 2017 The Authors British Journal of Developmental Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

Myeloma Cell Dynamics in Response to Treatment Supports a Model of Hierarchical Differentiation and Clonal Evolution.

PubMed

Tang, Min; Zhao, Rui; van de Velde, Helgi; Tross, Jennifer G; Mitsiades, Constantine; Viselli, Suzanne; Neuwirth, Rachel; Esseltine, Dixie-Lee; Anderson, Kenneth; Ghobrial, Irene M; San Miguel, Jesús F; Richardson, Paul G; Tomasson, Michael H; Michor, Franziska

2016-08-15

Since the pioneering work of Salmon and Durie, quantitative measures of tumor burden in multiple myeloma have been used to make clinical predictions and model tumor growth. However, such quantitative analyses have not yet been performed on large datasets from trials using modern chemotherapy regimens. We analyzed a large set of tumor response data from three randomized controlled trials of bortezomib-based chemotherapy regimens (total sample size n = 1,469 patients) to establish and validate a novel mathematical model of multiple myeloma cell dynamics. Treatment dynamics in newly diagnosed patients were most consistent with a model postulating two tumor cell subpopulations, "progenitor cells" and "differentiated cells." Differential treatment responses were observed with significant tumoricidal effects on differentiated cells and less clear effects on progenitor cells. We validated this model using a second trial of newly diagnosed patients and a third trial of refractory patients. When applying our model to data of relapsed patients, we found that a hybrid model incorporating both a differentiation hierarchy and clonal evolution best explains the response patterns. The clinical data, together with mathematical modeling, suggest that bortezomib-based therapy exerts a selection pressure on myeloma cells that can shape the disease phenotype, thereby generating further inter-patient variability. This model may be a useful tool for improving our understanding of disease biology and the response to chemotherapy regimens. Clin Cancer Res; 22(16); 4206-14. ©2016 AACR. ©2016 American Association for Cancer Research.

In-vivo determination of chewing patterns using FBG and artificial neural networks

NASA Astrophysics Data System (ADS)

Pegorini, Vinicius; Zen Karam, Leandro; Rocha Pitta, Christiano S.; Ribeiro, Richardson; Simioni Assmann, Tangriani; Cardozo da Silva, Jean Carlos; Bertotti, Fábio L.; Kalinowski, Hypolito J.; Cardoso, Rafael

2015-09-01

This paper reports the process of pattern classification of the chewing process of ruminants. We propose a simplified signal processing scheme for optical fiber Bragg grating (FBG) sensors based on machine learning techniques. The FBG sensors measure the biomechanical forces during jaw movements and an artificial neural network is responsible for the classification of the associated chewing pattern. In this study, three patterns associated to dietary supplement, hay and ryegrass were considered. Additionally, two other important events for ingestive behavior studies were monitored, rumination and idle period. Experimental results show that the proposed approach for pattern classification has been capable of differentiating the materials involved in the chewing process with a small classification error.

Differential flank growth

NASA Astrophysics Data System (ADS)

Zieschang, H. E.; Sievers, A.

1994-08-01

With the mathematical basis for the precise analysis of developmental processes in plants, the patterns of growth in phototropic and gravitropic responses have become better understood. A detailed temporal and spatial quantification of a growth process is an important tool for evaluating hypotheses about the underlying physiological mechanisms. Studies of growth rates and curvature show that the original Cholodny-Went hypothesis cannot explain the complex growth patterns during tropic responses of shoots and roots. In addition, regulating factors other than the lateral redistribution of hormones must be taken into account. Electrophysiological studies on roots led to a modification of the Cholodny-Went hypothesis in that redistributions of bioelectrical activities are observed.

Exposure to air pollution interacts with obesogenic nutrition to induce tissue-specific response patterns.

PubMed

Pardo, Michal; Kuperman, Yael; Levin, Liron; Rudich, Assaf; Haim, Yulia; Schauer, James J; Chen, Alon; Rudich, Yinon

2018-04-20

Obesity and exposure to particular matter (PM) have become two leading global threats to public health. However, the exact mechanisms and tissue-specificity of their health effects are largely unknown. Here we investigate whether a metabolic challenge (early nutritional obesity) synergistically interacts with an environmental challenge (PM exposure) to alter genes representing key response pathways, in a tissue-specific manner. Mice subjected to 7 weeks obesogenic nutrition were exposed every other day during the final week and a half to aqueous extracts of PM collected in the city of London (UK). The expression of 61 selected genes representing key response pathways were investigated in lung, liver, white and brown adipose tissues. Principal component analysis (PCA) revealed distinct patterns of expression changes between the 4 tissues, particularly in the lungs and the liver. Surprisingly, the lung responded to the nutrition challenge. The response of these organs to the PM challenge displayed opposite patterns for some key genes, in particular, those related to the Nrf2 pathway. While the contribution to the variance in gene expression changes in mice exposed to the combined challenge were largely similar among the tissues in PCA1, PCA2 exhibited predominant contribution of inflammatory and oxidative stress responses to the variance in the lungs, and a greater contribution of autophagy genes and MAP kinases in adipose tissues. Possible involvement of alterations in DNA methylation was demonstrated by cell-type-specific responses to a methylation inhibitor. Correspondingly, the DNA methyltransferase Dnmt3a2 increased in the lungs but decreased in the liver, demonstrating potential tissue-differential synergism between nutritional and PM exposure. The results suggest that urban PM, containing dissolved metals, interacts with obesogenic nutrition to regulate diverse response pathways including inflammation and oxidative stress, in a tissue-specific manner. Tissue-differential effects on DNA methylation may underlie tissue-specific responses to key stress-response genes such as catalase and Nrf2. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cell adhesion molecules expression pattern indicates that somatic cells arbitrate gonadal sex of differentiating bipotential fetal mouse gonad.

PubMed

Piprek, Rafal P; Kolasa, Michal; Podkowa, Dagmara; Kloc, Malgorzata; Kubiak, Jacek Z

2017-10-01

Unlike other organ anlagens, the primordial gonad is sexually bipotential in all animals. In mouse, the bipotential gonad differentiates into testis or ovary depending on the genetic sex (XY or XX) of the fetus. During gonad development cells segregate, depending on genetic sex, into distinct compartments: testis cords and interstitium form in XY gonad, and germ cell cysts and stroma in XX gonad. However, our knowledge of mechanisms governing gonadal sex differentiation remains very vague. Because it is known that adhesion molecules (CAMs) play a key role in organogenesis, we suspected that diversified expression of CAMs should also play a crucial role in gonad development. Using microarray analysis we identified 129 CAMs and factors regulating cell adhesion during sexual differentiation of mouse gonad. To identify genes expressed differentially in three cell lines in XY and XX gonads: i) supporting (Sertoli or follicular cells), ii) interstitial or stromal cells, and iii) germ cells, we used transgenic mice expressing EGFP reporter gene and FACS cell sorting. Although a large number of CAMs expressed ubiquitously, expression of certain genes was cell line- and genetic sex-specific. The sets of CAMs differentially expressed in supporting versus interstitial/stromal cells may be responsible for segregation of these two cell lines during gonadal development. There was also a significant difference in CAMs expression pattern between XY supporting (Sertoli) and XX supporting (follicular) cells but not between XY and XX germ cells. This indicates that differential CAMs expression pattern in the somatic cells but not in the germ line arbitrates structural organization of gonadal anlagen into testis or ovary. Copyright © 2017 Elsevier B.V. All rights reserved.

The expanding universe of T-cell subsets: Th1, Th2 and more.

PubMed

Mosmann, T R; Sad, S

1996-03-01

Since their discovery nearly ten years ago, T helper 1 (Th1) and Th2 subsets have been implicated in the regulation of many immune responses. In this article, Tim Mosmann and Subash Sad discuss the increasing number of T-cell subsets defined by cytokine patterns; the differentiation pathways of CD4+ and CD8+ T cells; the contribution of other cell types to these patterns; and the cytokine interactions during infection and pregnancy.

Framing the ultimatum game: gender differences and autonomic responses.

PubMed

Sarlo, Michela; Lotto, Lorella; Palomba, Daniela; Scozzari, Simona; Rumiati, Rino

2013-01-01

The present study aimed at investigating whether the way offers are framed in the Ultimatum Game (UG) affects behavioral and autonomic responses in men and women. The "I give you" and "I take" expressions were used as gain and loss frames, respectively. Skin conductance and heart rate were recorded as indices of autonomic activation in response to unfair, mid-value, and fair offers. Acceptance rates were higher in men than in women under the gain frame. Moreover, men showed higher acceptance rates under the gain than under the loss frame with mid-value offers, whereas women's choices were not affected by frame. On the physiological level, men produced differential autonomic response patterns during decision-making when offers were presented under gain and loss framing. The "I take" frame, by acting as a loss frame, elicited in men the characteristic defensive response pattern that is evoked by aversive stimulation, in which increases in skin conductance are coupled with increases in heart rate. On the other hand, the "I give you" frame, by acting as a gain frame, elicited in men increases in skin conductance associated with prevailing heart rate deceleratory responses, reflecting a state of enhanced attention and orienting. In contrast, women's autonomic reactivity was not affected by frame, consistent with behavioral results. Phasic changes in heart rate were crucial in revealing differential functional significance of skin conductance responses under different frames in men, thus questioning the assumption that this autonomic measure can be used as an index of negative emotional arousal in the UG.

Genetic diversity and differentiation in a wide ranging anadromous fish, American shad (Alosa sapidissima), is correlated with latitude.

PubMed

Hasselman, Daniel J; Ricard, Daniel; Bentzen, Paul

2013-03-01

Studies that span entire species ranges can provide insight into the relative roles of historical contingency and contemporary factors that influence population structure and can reveal patterns of genetic variation that might otherwise go undetected. American shad is a wide ranging anadromous clupeid fish that exhibits variation in demographic histories and reproductive strategies (both semelparity and iteroparity) and provides a unique perspective on the evolutionary processes that govern the genetic architecture of anadromous fishes. Using 13 microsatellite loci, we examined the magnitude and spatial distribution of genetic variation among 33 populations across the species' range to (i) determine whether signals of historical demography persist among contemporary populations and (ii) assess the effect of different reproductive strategies on population structure. Patterns of genetic diversity and differentiation among populations varied widely and reflect the differential influences of historical demography, microevolutionary processes and anthropogenic factors across the species' range. Sequential reductions of diversity with latitude among formerly glaciated rivers are consistent with stepwise postglacial colonization and successive population founder events. Weak differentiation among U.S. iteroparous populations may be a consequence of human-mediated gene flow, while weak differentiation among semelparous populations probably reflects natural gene flow. Evidence for an effect of reproductive strategy on population structure suggests an important role for environmental variation and suggests that the factors that are responsible for shaping American shad life history patterns may also influence population genetic structure. © 2013 Blackwell Publishing Ltd.

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

PubMed

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

2012-03-01

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

Lack of genetic structure among ecologically adapted populations of an Australian rainforest Drosophila species as indicated by microsatellite markers and mitochondrial DNA sequences.

PubMed

Schiffer, Michele; Kennington, W J; Hoffmann, A A; Blacket, M J

2007-04-01

Although fragmented rainforest environments represent hotspots for invertebrate biodiversity, few genetic studies have been conducted on rainforest invertebrates. Thus, it is not known if invertebrate species in rainforests are highly genetically fragmented, with the potential for populations to show divergent selection responses, or if there are low levels of gene flow sufficient to maintain genetic homogeneity among fragmented populations. Here we use microsatellite markers and DNA sequences from the mitochondrial ND5 locus to investigate genetic differences among Drosophila birchii populations from tropical rainforests in Queensland, Australia. As found in a previous study, mitochondrial DNA diversity was low with no evidence for population differentiation among rainforest fragments. The pattern of mitochondrial haplotype variation was consistent with D. birchii having undergone substantial past population growth. Levels of nuclear genetic variation were high in all populations while F(ST) values were very low, even for flies from geographically isolated areas of rainforest. No significant differentiation was observed between populations on either side of the Burdekin Gap (a long-term dry corridor), although there was evidence for higher gene diversity in low-latitude populations. Spatial autocorrelation coefficients were low and did not differ significantly from random, except for one locus which revealed a clinal-like pattern. Comparisons of microsatellite differentiation contrasted with previously established clinal patterns in quantitative traits in D. birchii, and indicate that the patterns in quantitative traits are likely to be due to selection. These results suggest moderate gene flow in D. birchii over large distances. Limited population structure in this species appears to be due to recent range expansions or cycles of local extinctions followed by recolonizations/expansions. Nevertheless, patterns of local adaptation have developed in D. birchii that may result in populations showing different selection responses when faced with environmental change.

Identification of host genes leading to West Nile virus encephalitis in mice brain using RNA-seq analysis

PubMed Central

Kumar, Mukesh; Belcaid, Mahdi; Nerurkar, Vivek R.

2016-01-01

Differential host responses may be critical determinants of distinct pathologies of West Nile virus (WNV) NY99 (pathogenic) and WNV Eg101 (non-pathogenic) strains. We employed RNA-seq technology to analyze global differential gene expression in WNV-infected mice brain and to identify the host cellular factors leading to lethal encephalitis. We identified 1,400 and 278 transcripts, which were differentially expressed after WNV NY99 and WNV Eg101 infections, respectively, and 147 genes were common to infection with both the viruses. Genes that were up-regulated in infection with both the viruses were mainly associated with interferon signaling. Genes associated with inflammation and cell death/apoptosis were only expressed after WNV NY99 infection. We demonstrate that differences in the activation of key pattern recognition receptors resulted in the induction of unique innate immune profiles, which corresponded with the induction of interferon and inflammatory responses. Pathway analysis of differentially expressed genes indicated that after WNV NY99 infection, TREM-1 mediated activation of toll-like receptors leads to the high inflammatory response. In conclusion, we have identified both common and specific responses to WNV NY99 and WNV Eg101 infections as well as genes linked to potential resistance to infection that may be targets for therapeutics. PMID:27211830

Unravelling a biogeographical knot: origin of the 'leapfrog' distribution pattern of Australo-Papuan sooty owls (Strigiformes) and logrunners (Passeriformes).

PubMed Central

Norman, J A; Christidis, L; Joseph, L; Slikas, B; Alpers, D

2002-01-01

Molecular analysis of two Australo-Papuan rainforest birds exhibiting correlated 'leapfrog' patterns were used to elucidate the evolutionary origin of this unusual pattern of geographical differentiation. In both sooty owls (Tyto) and logrunners (Orthonyx), phenotypically similar populations occupy widely disjunct areas (central-eastern Australia and upland New Guinea) with a third, highly distinctive population, occurring between them in northeastern Queensland. Two mechanisms have been proposed to explain the origin of leapfrog patterns in avian distributions: recent shared ancestry of terminal populations and unequal rates or phenotypic change among populations. As the former should generate correlated patterns of phenotypic and genetic differentiation, we tested for a sister relationship between populations from New Guinea and central-eastern Australia using nuclear and mitochondrial DNA sequences. The resulting phylogenies not only refute recent ancestry as an explanation for the leapfrog pattern, but provide evidence of vastly different spatio-temporal histories for sooty owls and logrunners within the Australo-Papuan rainforests. This incongruence indicates that the evolutionary processes responsible for generating leapfrog patterns in these co-distributed taxa are complex, possibly involving a combination of selection and drift in sooty owls and convergence or retention of ancestral characteristics in logrunners. PMID:12396487

Differential Accumulation of Sunflower Tetraubiquitin mRNAs during Zygotic Embryogenesis and Developmental Regulation of Their Heat-Shock Response.

PubMed Central

Almoguera, C.; Coca, M. A.; Jordano, J.

1995-01-01

We have isolated and sequenced Ha UbiS, a cDNA for a dry-seed-stored mRNA that encodes tetraubiquitin. We have observed differential accumulation of tetraubiquitin mRNAs during sunflower (Helianthus annuus L.) zygotic embryogenesis. These mRNAs were up-regulated during late embryogenesis and reached higher prevalence in the dry seed, where they were found to be associated mainly with provascular tissue. UbiS mRNA, as confirmed by Rnase A protection experiments, accumulated also in response to heat shock, but only in leaves and later during postgerminative development. These novel observations demonstrate expression during seed maturation of specific plant polyubiquitin transcripts and developmental regulation of their heat-shock response. Using ubiquitin antibodies we also detected discrete, seed-specific proteins with distinct temporal expression patterns during zygotic embryogenesis. Some of these patterns were concurrent with UbiS mRNA accumulation in seeds. The most abundant ubiquitin-reacting proteins found in mature seeds were small (16-22 kD) and acidic (isoelectric points of 6.1-7.4). Possible functional implications for UbiS expression elicited from these observations are discussed. PMID:12228401

Selective deficit in spatial memory strategies contrast to intact response strategies in patients with schizophrenia spectrum disorders tested in a virtual navigation task.

PubMed

Wilkins, Leanne K; Girard, Todd A; Konishi, Kyoko; King, Matthew; Herdman, Katherine A; King, Jelena; Christensen, Bruce; Bohbot, Veronique D

2013-11-01

Spatial memory is impaired among persons with schizophrenia (SCZ). However, different strategies may be used to solve most spatial memory and navigation tasks. This study investigated the hypothesis that participants with schizophrenia-spectrum disorders (SSD) would demonstrate differential impairment during acquisition and retrieval of target locations when using a hippocampal-dependent spatial strategy, but not a response strategy, which is more associated with caudate function. Healthy control (CON) and SSD participants were tested using the 4-on-8 virtual maze (4/8VM), a virtual navigation task designed to differentiate between participants' use of spatial and response strategies. Consistent with our predictions, SSD participants demonstrated a differential deficit such that those who navigated using a spatial strategy made more errors and took longer to locate targets. In contrast, SSD participants who spontaneously used a response strategy performed as well as CON participants. The differential pattern of spatial-memory impairment in SSD provides only indirect support for underlying hippocampal dysfunction. These findings emphasize the importance of considering individual strategies when investigating SSD-related memory and navigation performance. Future cognitive intervention protocols may harness SSD participants' intact ability to navigate using a response strategy and/or train the deficient ability to navigate using a spatial strategy to improve navigation and memory abilities in participants with SSD. Copyright © 2013 Wiley Periodicals, Inc.

Arabidopsis gene expression patterns are altered during spaceflight

NASA Astrophysics Data System (ADS)

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

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

Activity Participation and Sensory Features among Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Little, Lauren M.; Ausderau, Karla; Sideris, John; Baranek, Grace T.

2015-01-01

Sensory features are highly prevalent among children with autism spectrum disorders (ASD) and have been shown to cluster into four patterns of response, including hyperresponsiveness, hyporesponsiveness, enhanced perception, and sensory interests, repetitions and seeking behaviors. Given the lack of large-scale research on the differential effects…

Molecular Analysis of SCARECROW Genes Expressed in White Lupin Cluster Roots

USDA-ARS?s Scientific Manuscript database

The Scarecrow (SCR) transcription factor plays a crucial role in root cell radial patterning and is required for maintenance of the quiescent center and differentiation of the endodermis. In response to phosphorus (P) deficiency, white lupin (Lupinus albus L.) root surface area increases some 50- to...

Activation of the JAK-STAT Signaling Pathway after In Vitro Stimulation with IFNß in Multiple Sclerosis Patients According to the Therapeutic Response to IFNß

PubMed Central

Hurtado-Guerrero, Isaac; Pinto-Medel, Maria Jesús; Urbaneja, Patricia; Rodriguez- Bada, Jose Luis; León, Antonio; Guerrero, Miguel; Fernández, Óscar

2017-01-01

Interferon beta (IFNß) is a common treatment used for multiple sclerosis (MS) which acts through the activation of the JAK-STAT pathway. However, this therapy is not always effective and currently there are no reliable biomarkers to predict therapeutic response. We postulate that the heterogeneity in the response to IFNß therapy could be related to differential activation patterns of the JAK-STAT signaling pathway. Our aim was to evaluate the basal levels and the short term activation of this pathway after IFNß stimulation in untreated and IFNß treated patients, as well as according to therapeutic response. Therefore, cell surface levels of IFNAR subunits (IFNAR1 and IFNAR2) and the activated forms of STAT1 and STAT2 were assessed in peripheral blood mononuclear cells from MS patients by flow cytometry. Basal levels of each of the markers strongly correlated with the expression of the others in untreated patients, but many of these correlations lost significance in treated patients and after short term activation with IFNß. Patients who had undergone IFNß treatment showed higher basal levels of IFNAR1 and pSTAT1, but a reduced response to in vitro exposure to IFNß. Conversely, untreated patients, with lower basal levels, showed a greater ability of short term activation of this pathway. Monocytes from responder patients had lower IFNAR1 levels (p = 0.039) and higher IFNAR2 levels (p = 0.035) than non-responders just after IFNß stimulation. A cluster analysis showed that levels of IFNAR1, IFNAR2 and pSTAT1-2 in monocytes grouped 13 out of 19 responder patients with a similar expression pattern, showing an association of this pattern with the phenotype of good response to IFNß (p = 0.013). Our findings suggest that an activation pattern of the IFNß signaling pathway in monocytes could be associated with a clinical phenotype of good response to IFNß treatment and that a differential modulation of the IFNAR subunits in monocytes could be related with treatment effectiveness. PMID:28103257

Large-scale transcriptome analysis reveals arabidopsis metabolic pathways are frequently influenced by different pathogens.

PubMed

Jiang, Zhenhong; He, Fei; Zhang, Ziding

2017-07-01

Through large-scale transcriptional data analyses, we highlighted the importance of plant metabolism in plant immunity and identified 26 metabolic pathways that were frequently influenced by the infection of 14 different pathogens. Reprogramming of plant metabolism is a common phenomenon in plant defense responses. Currently, a large number of transcriptional profiles of infected tissues in Arabidopsis (Arabidopsis thaliana) have been deposited in public databases, which provides a great opportunity to understand the expression patterns of metabolic pathways during plant defense responses at the systems level. Here, we performed a large-scale transcriptome analysis based on 135 previously published expression samples, including 14 different pathogens, to explore the expression pattern of Arabidopsis metabolic pathways. Overall, metabolic genes are significantly changed in expression during plant defense responses. Upregulated metabolic genes are enriched on defense responses, and downregulated genes are enriched on photosynthesis, fatty acid and lipid metabolic processes. Gene set enrichment analysis (GSEA) identifies 26 frequently differentially expressed metabolic pathways (FreDE_Paths) that are differentially expressed in more than 60% of infected samples. These pathways are involved in the generation of energy, fatty acid and lipid metabolism as well as secondary metabolite biosynthesis. Clustering analysis based on the expression levels of these 26 metabolic pathways clearly distinguishes infected and control samples, further suggesting the importance of these metabolic pathways in plant defense responses. By comparing with FreDE_Paths from abiotic stresses, we find that the expression patterns of 26 FreDE_Paths from biotic stresses are more consistent across different infected samples. By investigating the expression correlation between transcriptional factors (TFs) and FreDE_Paths, we identify several notable relationships. Collectively, the current study will deepen our understanding of plant metabolism in plant immunity and provide new insights into disease-resistant crop improvement.

Development of visual cortical function in infant macaques: A BOLD fMRI study

PubMed Central

Meeson, Alan; Munk, Matthias H. J.; Kourtzi, Zoe; Movshon, J. Anthony; Logothetis, Nikos K.; Kiorpes, Lynne

2017-01-01

Functional brain development is not well understood. In the visual system, neurophysiological studies in nonhuman primates show quite mature neuronal properties near birth although visual function is itself quite immature and continues to develop over many months or years after birth. Our goal was to assess the relative development of two main visual processing streams, dorsal and ventral, using BOLD fMRI in an attempt to understand the global mechanisms that support the maturation of visual behavior. Seven infant macaque monkeys (Macaca mulatta) were repeatedly scanned, while anesthetized, over an age range of 102 to 1431 days. Large rotating checkerboard stimuli induced BOLD activation in visual cortices at early ages. Additionally we used static and dynamic Glass pattern stimuli to probe BOLD responses in primary visual cortex and two extrastriate areas: V4 and MT-V5. The resulting activations were analyzed with standard GLM and multivoxel pattern analysis (MVPA) approaches. We analyzed three contrasts: Glass pattern present/absent, static/dynamic Glass pattern presentation, and structured/random Glass pattern form. For both GLM and MVPA approaches, robust coherent BOLD activation appeared relatively late in comparison to the maturation of known neuronal properties and the development of behavioral sensitivity to Glass patterns. Robust differential activity to Glass pattern present/absent and dynamic/static stimulus presentation appeared first in V1, followed by V4 and MT-V5 at older ages; there was no reliable distinction between the two extrastriate areas. A similar pattern of results was obtained with the two analysis methods, although MVPA analysis showed reliable differential responses emerging at later ages than GLM. Although BOLD responses to large visual stimuli are detectable, our results with more refined stimuli indicate that global BOLD activity changes as behavioral performance matures. This reflects an hierarchical development of the visual pathways. Since fMRI BOLD reflects neural activity on a population level, our results indicate that, although individual neurons might be adult-like, a longer maturation process takes place on a population level. PMID:29145469

Expression patterns of members of the ethylene signaling-related gene families in response to dehydration stresses in cassava.

PubMed

Ren, Meng Yun; Feng, Ren Jun; Shi, Hou Rui; Lu, Li Fang; Yun, Tian Yan; Peng, Ming; Guan, Xiao; Zhang, Heng; Wang, Jing Yi; Zhang, Xi Yan; Li, Cheng Liang; Chen, Yan Jun; He, Peng; Zhang, Yin Dong; Xie, Jiang Hui

2017-01-01

Drought is the one of the most important environment stresses that restricts crop yield worldwide. Cassava (Manihot esculenta Crantz) is an important food and energy crop that has many desirable traits such as drought, heat and low nutrients tolerance. However, the mechanisms underlying drought tolerance in cassava are unclear. Ethylene signaling pathway, from the upstream receptors to the downstream transcription factors, plays important roles in environmental stress responses during plant growth and development. In this study, we used bioinformatics approaches to identify and characterize candidate Manihot esculenta ethylene receptor genes and transcription factor genes. Using computational methods, we localized these genes on cassava chromosomes, constructed phylogenetic trees and identified stress-responsive cis-elements within their 5' upstream regions. Additionally, we measured the trehalose and proline contents in cassava fresh leaves after drought, osmotic, and salt stress treatments, and then it was found that the regulation patterns of contents of proline and trehalose in response to various dehydration stresses were differential, or even the opposite, which shows that plant may take different coping strategies to deal with different stresses, when stresses come. Furthermore, expression profiles of these genes in different organs and tissues under non-stress and abiotic stress were investigated through quantitative real-time PCR (qRT-PCR) analyses in cassava. Expression profiles exhibited clear differences among different tissues under non-stress and various dehydration stress conditions. We found that the leaf and tuberous root tissues had the greatest and least responses, respectively, to drought stress through the ethylene signaling pathway in cassava. Moreover, tuber and root tissues had the greatest and least reponses to osmotic and salt stresses through ethylene signaling in cassava, respectively. These results show that these plant tissues had differential expression levels of genes involved in ethylene signaling in response to the stresses tested. Moreover, after several gene duplication events, the spatiotemporally differential expression pattern of homologous genes in response to abiotic and biotic stresses may imply their functional diversity as a mechanism for adapting to the environment. Our data provide a framework for further research on the molecular mechanisms of cassava resistance to drought stress and provide a foundation for breeding drought-resistant new cultivars.

Expression patterns of members of the ethylene signaling–related gene families in response to dehydration stresses in cassava

PubMed Central

Shi, Hou Rui; Lu, Li Fang; Yun, Tian Yan; Peng, Ming; Guan, Xiao; Zhang, Heng; Wang, Jing Yi; Zhang, Xi Yan; Li, Cheng Liang; Chen, Yan Jun; He, Peng; Zhang, Yin Dong; Xie, Jiang Hui

2017-01-01

Drought is the one of the most important environment stresses that restricts crop yield worldwide. Cassava (Manihot esculenta Crantz) is an important food and energy crop that has many desirable traits such as drought, heat and low nutrients tolerance. However, the mechanisms underlying drought tolerance in cassava are unclear. Ethylene signaling pathway, from the upstream receptors to the downstream transcription factors, plays important roles in environmental stress responses during plant growth and development. In this study, we used bioinformatics approaches to identify and characterize candidate Manihot esculenta ethylene receptor genes and transcription factor genes. Using computational methods, we localized these genes on cassava chromosomes, constructed phylogenetic trees and identified stress-responsive cis-elements within their 5’ upstream regions. Additionally, we measured the trehalose and proline contents in cassava fresh leaves after drought, osmotic, and salt stress treatments, and then it was found that the regulation patterns of contents of proline and trehalose in response to various dehydration stresses were differential, or even the opposite, which shows that plant may take different coping strategies to deal with different stresses, when stresses come. Furthermore, expression profiles of these genes in different organs and tissues under non-stress and abiotic stress were investigated through quantitative real-time PCR (qRT-PCR) analyses in cassava. Expression profiles exhibited clear differences among different tissues under non-stress and various dehydration stress conditions. We found that the leaf and tuberous root tissues had the greatest and least responses, respectively, to drought stress through the ethylene signaling pathway in cassava. Moreover, tuber and root tissues had the greatest and least reponses to osmotic and salt stresses through ethylene signaling in cassava, respectively. These results show that these plant tissues had differential expression levels of genes involved in ethylene signaling in response to the stresses tested. Moreover, after several gene duplication events, the spatiotemporally differential expression pattern of homologous genes in response to abiotic and biotic stresses may imply their functional diversity as a mechanism for adapting to the environment. Our data provide a framework for further research on the molecular mechanisms of cassava resistance to drought stress and provide a foundation for breeding drought-resistant new cultivars. PMID:28542282

Differential Transcriptional Response in Macrophages Infected with Cell Wall Deficient versus Normal Mycobacterium Tuberculosis

PubMed Central

Fu, Yu-Rong; Gao, Kun-Shan; Ji, Rui; Yi, Zheng-Jun

2015-01-01

Host-pathogen interactions determine the outcome following infection by mycobacterium tuberculosis (Mtb). Under adverse circumstances, normal Mtb can form cell-wall deficient (CWD) variants within macrophages, which have been considered an adaptive strategy for facilitating bacterial survival inside macrophages. However, the molecular mechanism by which infection of macrophages with different phenotypic Mtb elicits distinct responses of macrophages is not fully understood. To explore the molecular events triggered upon Mtb infection of macrophages, differential transcriptional responses of RAW264.7 cells infected with two forms of Mtb, CWD-Mtb and normal Mtb, were studied by microarray analysis. Some of the differentially regulated genes were confirmed by RT-qPCR in both RAW264.7 cells and primary macrophages. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was used to analyze functions of differentially expressed genes. Distinct gene expression patterns were observed between CWD-Mtb and normal Mtb group. Mapt was up-regulated, while NOS2 and IL-11 were down-regulated in CWD-Mtb infected RAW264.7 cells and primary macrophages compared with normal Mtb infected ones. Many deregulated genes were found to be related to macrophages activation, immune response, phagosome maturation, autophagy and lipid metabolism. KEGG analysis showed that the differentially expressed genes were mainly involved in MAPK signaling pathway, nitrogen metabolism, cytokine-cytokine receptor interaction and focal adhesion. Taken together, the present study showed that differential macrophage responses were induced by intracellular CWD-Mtb an normal Mtb infection, which suggested that interactions between macrophages and different phenotypic Mtb are very complex. The results provide evidence for further understanding of pathogenesis of CWD-Mtb and may help in improving strategies to eliminate intracellular CWD-Mtb. PMID:25552926

Differences in dehydration tolerance among populations of a gametophyte-only fern.

PubMed

Chambers, Sally M; Watkins, J E; Sessa, Emily B

2017-04-01

For many plant species, historical climatic conditions may have left lasting imprints that are detectable in contemporary populations. Additionally, if these historical conditions also prevented gene flow among populations, these populations may be differentiated with respect to one another and their contemporary environmental conditions. For the fern, Vittaria appalachiana , one theory is that historical conditions during the Pleistocene largely shaped both the distribution and lack of sporophyte production. Our goals-based on this theory-were to examine physiological differences among and within populations spanning the species' geographic range, and the contribution of historical climatic conditions to this differentiation. We exposed explants from five populations to four drying treatments and examined differences in physiological response. Additionally, we examined the role of historical and current climatic conditions in driving the observed population differentiation. Populations differ in their ability to tolerate varying levels of dehydration, displaying a pattern of countergradient selection. Exposure to historical and contemporary climatic conditions, specifically variation in temperature and precipitation regimes, resulted in population divergence observed among contemporary populations. Historical conditions have shaped not only the distribution of V. appalachiana , but also its current physiological limitations. Results from this study support the hypothesis that climatic conditions during the Pleistocene are responsible for the distribution of this species, and may be responsible for the observed differences in dehydration tolerance. Additionally, dehydration tolerance may be the driving factor for previously reported patterns of countergradient selection in this species. © 2017 Botanical Society of America.

Evidence of an evolutionary hourglass pattern in herbivory-induced transcriptomic responses.

PubMed

Durrant, Matthew; Boyer, Justin; Zhou, Wenwu; Baldwin, Ian T; Xu, Shuqing

2017-08-01

Herbivory-induced defenses are specific and activated in plants when elicitors, frequently found in the herbivores' oral secretions, are introduced into wounds during attack. While complex signaling cascades are known to be involved, it remains largely unclear how natural selection has shaped the evolution of these induced defenses. We analyzed herbivory-induced transcriptomic responses in wild tobacco, Nicotiana attenuata, using a phylotranscriptomic approach that measures the origin and sequence divergence of herbivory-induced genes. Highly conserved and evolutionarily ancient genes of primary metabolism were activated at intermediate time points (2-6 h) after elicitation, while less constrained and young genes associated with defense signaling and biosynthesis of specialized metabolites were activated at early (before 2 h) and late (after 6 h) stages of the induced response, respectively - a pattern resembling the evolutionary hourglass pattern observed during embryogenesis in animals and the developmental process in plants and fungi. The hourglass patterns found in herbivory-induced defense responses and developmental process are both likely to be a result of signaling modularization and differential evolutionary constraints on the modules involved in the signaling cascade. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Discovering causal signaling pathways through gene-expression patterns

PubMed Central

Parikh, Jignesh R.; Klinger, Bertram; Xia, Yu; Marto, Jarrod A.; Blüthgen, Nils

2010-01-01

High-throughput gene-expression studies result in lists of differentially expressed genes. Most current meta-analyses of these gene lists include searching for significant membership of the translated proteins in various signaling pathways. However, such membership enrichment algorithms do not provide insight into which pathways caused the genes to be differentially expressed in the first place. Here, we present an intuitive approach for discovering upstream signaling pathways responsible for regulating these differentially expressed genes. We identify consistently regulated signature genes specific for signal transduction pathways from a panel of single-pathway perturbation experiments. An algorithm that detects overrepresentation of these signature genes in a gene group of interest is used to infer the signaling pathway responsible for regulation. We expose our novel resource and algorithm through a web server called SPEED: Signaling Pathway Enrichment using Experimental Data sets. SPEED can be freely accessed at http://speed.sys-bio.net/. PMID:20494976

Paleoclimate diagnostics: consistent large-scale temperature responses in warm and cold climates

NASA Astrophysics Data System (ADS)

Izumi, Kenji; Bartlein, Patrick; Harrison, Sandy

2015-04-01

The CMIP5 model simulations of the large-scale temperature responses to increased raditative forcing include enhanced land-ocean contrast, stronger response at higher latitudes than in the tropics, and differential responses in warm and cool season climates to uniform forcing. Here we show that these patterns are also characteristic of CMIP5 model simulations of past climates. The differences in the responses over land as opposed to over the ocean, between high and low latitudes, and between summer and winter are remarkably consistent (proportional and nearly linear) across simulations of both cold and warm climates. Similar patterns also appear in historical observations and paleoclimatic reconstructions, implying that such responses are characteristic features of the climate system and not simple model artifacts, thereby increasing our confidence in the ability of climate models to correctly simulate different climatic states. We also show the possibility that a small set of common mechanisms control these large-scale responses of the climate system across multiple states.

Ripple/Carcinoid pattern sebaceoma with apocrine differentiation.

PubMed

Misago, Noriyuki; Narisawa, Yutaka

2011-02-01

Sebaceoma is a benign sebaceous neoplasm, which has been reported to show characteristic growth patterns, such as, ripple, labyrinthine/sinusoidal, and carcinoid-like patterns. Another recent finding regarding in sebaceoma is the observation of apocrine differentiation within the sebaceoma lesion. This report describes a case of carcinoid (a partial ripple and labyrinthine) pattern sebaceoma with apocrine differentiation with a literature review and immunohistochemical studies. The various characteristic growth patterns in sebaceoma were suggested to simply be variations of the same growth pattern arranged in cords, namely, a unified term "ripple/carcinoid pattern." The primitive sebaceous germinative cells in sebaceoma may still have the ability to undergo apocrine differentiation. Most of the reports so far on sebaceoma with apocrine differentiation, including the present case, describe a ripple/carcinoid pattern, thus suggesting that ripple/carcinoid pattern sebaceoma is composed of more primitive sebaceous germinative cells than conventional sebaceoma.

Brain activation in response to randomized visual stimulation as obtained from conjunction and differential analysis: an fMRI study

NASA Astrophysics Data System (ADS)

Nasaruddin, N. H.; Yusoff, A. N.; Kaur, S.

2014-11-01

The objective of this multiple-subjects functional magnetic resonance imaging (fMRI) study was to identify the common brain areas that are activated when viewing black-and-white checkerboard pattern stimuli of various shapes, pattern and size and to investigate specific brain areas that are involved in processing static and moving visual stimuli. Sixteen participants viewed the moving (expanding ring, rotating wedge, flipping hour glass and bowtie and arc quadrant) and static (full checkerboard) stimuli during an fMRI scan. All stimuli have black-and-white checkerboard pattern. Statistical parametric mapping (SPM) was used in generating brain activation. Differential analyses were implemented to separately search for areas involved in processing static and moving stimuli. In general, the stimuli of various shapes, pattern and size activated multiple brain areas mostly in the left hemisphere. The activation in the right middle temporal gyrus (MTG) was found to be significantly higher in processing moving visual stimuli as compared to static stimulus. In contrast, the activation in the left calcarine sulcus and left lingual gyrus were significantly higher for static stimulus as compared to moving stimuli. Visual stimulation of various shapes, pattern and size used in this study indicated left lateralization of activation. The involvement of the right MTG in processing moving visual information was evident from differential analysis, while the left calcarine sulcus and left lingual gyrus are the areas that are involved in the processing of static visual stimulus.

Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man.

PubMed

Kalafatakis, K; Russell, G M; Harmer, C J; Munafo, M R; Marchant, N; Wilson, A; Brooks, J C; Durant, C; Thakrar, J; Murphy, P; Thai, N J; Lightman, S L

2018-04-24

Glucocorticoids (GCs) are secreted in an ultradian, pulsatile pattern that emerges from delays in the feedforward-feedback interaction between the anterior pituitary and adrenal glands. Dynamic oscillations of GCs are critical for normal cognitive and metabolic function in the rat and have been shown to modulate the pattern of GC-sensitive gene expression, modify synaptic activity, and maintain stress responsiveness. In man, current cortisol replacement therapy does not reproduce physiological hormone pulses and is associated with psychopathological symptoms, especially apathy and attenuated motivation in engaging with daily activities. In this work, we tested the hypothesis that the pattern of GC dynamics in the brain is of crucial importance for regulating cognitive and behavioral processes. We provide evidence that exactly the same dose of cortisol administered in different patterns alters the neural processing underlying the response to emotional stimulation, the accuracy in recognition and attentional bias toward/away from emotional faces, the quality of sleep, and the working memory performance of healthy male volunteers. These data indicate that the pattern of the GC rhythm differentially impacts human cognition and behavior under physiological, nonstressful conditions and has major implications for the improvement of cortisol replacement therapy.

Disease relevant modifications of the methylome and transcriptome by particulate matter (PM2.5) from biomass combustion.

PubMed

Heßelbach, Katharina; Kim, Gwang-Jin; Flemming, Stephan; Häupl, Thomas; Bonin, Marc; Dornhof, Regina; Günther, Stefan; Merfort, Irmgard; Humar, Matjaz

2017-09-01

Exposure to particulate matter (PM) is recognized as a major health hazard, but molecular responses are still insufficiently described. We analyzed the epigenetic impact of ambient PM 2.5 from biomass combustion on the methylome of primary human bronchial epithelial BEAS-2B cells using the Illumina HumanMethylation450 BeadChip. The transcriptome was determined by the Affymetrix HG-U133 Plus 2.0 Array. PM 2.5 induced genome wide alterations of the DNA methylation pattern, including differentially methylated CpGs in the promoter region associated with CpG islands. Gene ontology analysis revealed that differentially methylated genes were significantly clustered in pathways associated with the extracellular matrix, cellular adhesion, function of GTPases, and responses to extracellular stimuli, or were involved in ion binding and shuttling. Differential methylations also affected tandem repeats. Additionally, 45 different miRNA CpG loci showed differential DNA methylation, most of them proximal to their promoter. These miRNAs are functionally relevant for lung cancer, inflammation, asthma, and other PM-associated diseases. Correlation of the methylome and transcriptome demonstrated a clear bias toward transcriptional activation by hypomethylation. Genes that exhibited both differential methylation and expression were functionally linked to cytokine and immune responses, cellular motility, angiogenesis, inflammation, wound healing, cell growth, differentiation and development, or responses to exogenous matter. Disease ontology of differentially methylated and expressed genes indicated their prominent role in lung cancer and their participation in dominant cancer related signaling pathways. Thus, in lung epithelial cells, PM 2.5 alters the methylome of genes and noncoding transcripts or elements that might be relevant for PM- and lung-associated diseases.

Disease relevant modifications of the methylome and transcriptome by particulate matter (PM2.5) from biomass combustion

PubMed Central

Heßelbach, Katharina; Kim, Gwang-Jin; Flemming, Stephan; Häupl, Thomas; Bonin, Marc; Dornhof, Regina; Günther, Stefan; Merfort, Irmgard; Humar, Matjaz

2017-01-01

ABSTRACT Exposure to particulate matter (PM) is recognized as a major health hazard, but molecular responses are still insufficiently described. We analyzed the epigenetic impact of ambient PM2.5 from biomass combustion on the methylome of primary human bronchial epithelial BEAS-2B cells using the Illumina HumanMethylation450 BeadChip. The transcriptome was determined by the Affymetrix HG-U133 Plus 2.0 Array. PM2.5 induced genome wide alterations of the DNA methylation pattern, including differentially methylated CpGs in the promoter region associated with CpG islands. Gene ontology analysis revealed that differentially methylated genes were significantly clustered in pathways associated with the extracellular matrix, cellular adhesion, function of GTPases, and responses to extracellular stimuli, or were involved in ion binding and shuttling. Differential methylations also affected tandem repeats. Additionally, 45 different miRNA CpG loci showed differential DNA methylation, most of them proximal to their promoter. These miRNAs are functionally relevant for lung cancer, inflammation, asthma, and other PM-associated diseases. Correlation of the methylome and transcriptome demonstrated a clear bias toward transcriptional activation by hypomethylation. Genes that exhibited both differential methylation and expression were functionally linked to cytokine and immune responses, cellular motility, angiogenesis, inflammation, wound healing, cell growth, differentiation and development, or responses to exogenous matter. Disease ontology of differentially methylated and expressed genes indicated their prominent role in lung cancer and their participation in dominant cancer related signaling pathways. Thus, in lung epithelial cells, PM2.5 alters the methylome of genes and noncoding transcripts or elements that might be relevant for PM- and lung-associated diseases. PMID:28742980

Vocal responses of austral forest frogs to amplitude and degradation patterns of advertisement calls.

PubMed

Penna, Mario; Moreno-Gómez, Felipe N; Muñoz, Matías I; Cisternas, Javiera

2017-07-01

Degradation phenomena affecting animal acoustic signals may provide cues to assess the distance of emitters. Recognition of degraded signals has been extensively demonstrated in birds, and recently studies have also reported detection of degraded patterns in anurans that call at or above ground level. In the current study we explore the vocal responses of the syntopic burrowing male frogs Eupsophus emiliopugini and E. calcaratus from the South American temperate forest to synthetic conspecific calls differing in amplitude and emulating degraded and non-degraded signal patterns. The results show a strong dependence of vocal responses on signal amplitude, and a general lack of differential responses to signals with different pulse amplitude modulation depths in E. emiliopugini and no effect of relative amplitude of harmonics in E. calcaratus. Such limited discrimination of signal degradation patterns from non-degraded signals is likely related to the burrowing habits of these species. Shelters amplify outgoing and incoming conspecific vocalizations, but do not counteract signal degradation to an extent comparable to calling strategies used by other frogs. The limited detection abilities and resultant response permissiveness to degraded calls in these syntopic burrowing species would be advantageous for animals communicating in circumstances in which signal alteration prevails. Copyright © 2017 Elsevier B.V. All rights reserved.

How time delay and network design shape response patterns in biochemical negative feedback systems.

PubMed

Börsch, Anastasiya; Schaber, Jörg

2016-08-24

Negative feedback in combination with time delay can bring about both sustained oscillations and adaptive behaviour in cellular networks. Here, we study which design features of systems with delayed negative feedback shape characteristic response patterns with special emphasis on the role of time delay. To this end, we analyse generic two-dimensional delay differential equations describing the dynamics of biochemical signal-response networks. We investigate the influence of several design features on the stability of the model equilibrium, i.e., presence of auto-inhibition and/or mass conservation and the kind and/or strength of the delayed negative feedback. We show that auto-inhibition and mass conservation have a stabilizing effect, whereas increasing abruptness and decreasing feedback threshold have a de-stabilizing effect on the model equilibrium. Moreover, applying our theoretical analysis to the mammalian p53 system we show that an auto-inhibitory feedback can decouple period and amplitude of an oscillatory response, whereas the delayed feedback can not. Our theoretical framework provides insight into how time delay and design features of biochemical networks act together to elicit specific characteristic response patterns. Such insight is useful for constructing synthetic networks and controlling their behaviour in response to external stimulation.

Masked priming for the comparative evaluation of camouflage conspicuity.

PubMed

Brunyé, Tad T; Eddy, Marianna D; Cain, Matthew S; Hepfinger, Lisa B; Rock, Kathryn

2017-07-01

Human observer test and evaluation of camouflage patterns is critical for understanding relative pattern conspicuity against a range of background scenes. However, very few validated methodologies exist for this purpose, and those that do carry several limitations. Five experiments examined whether masked priming with a dot probe could be used to reliably differentiate camouflage patterns. In each experiment, participants were primed with a camouflaged target appearing on the left or right of the screen, and then made a speeded response to a dot probe appearing on the same (congruent) or different (incongruent) side. Across experiments we parametrically varied prime duration between 35, 42, 49, 56, and 63 ms. Results demonstrated that as prime duration increased, a response time disadvantage for incongruent trials emerged with certain camouflage patterns. Interestingly, the most conspicuous patterns showed behavioral differences at a relatively brief (49 ms) prime duration, whereas behavioral differences were only found at longer prime durations for less conspicuous patterns; this overall results pattern matched that predicted by a visual salience model. Together, we demonstrate the viability of masked priming for the test and evaluation of camouflage patterns, and correlated outcomes for saliency models and primed object processing. Published by Elsevier Ltd.

Oligo-dT anchored cDNA-SCoT: a novel differential display method for analyzing differential gene expression in response to several stress treatments in mango (Mangifera indica L.).

PubMed

Luo, Cong; He, Xin-Hua; Hu, Ying; Yu, Hai-xia; Ou, Shi-Jin; Fang, Zhong-Bin

2014-09-15

Differential display is a powerful technique for analyzing differences in gene expression. Oligo-dT cDNAstart codon targeted marker (cDNA-SCoT) technique is a novel, simple, cheap, rapid, and efficient method for differential gene expression research. In the present study, the oligo-dT anchored cDNA-SCoT technique was exploited to identify differentially expressed genes during several stress treatments in mango. A total of 37 primers combined with oligo-dT anchor primers 3side amplified approximately 150 fragments of 150 bp to 1500 bp in length. Up to 100 fragments were differentially expressed among the stress treatments and control samples, among which 92 were obtained and sequenced. Out of the 92 transcript derived fragments (TDFs), 70% were highly homologous to known genes, and 30% encoded unclassified proteins with unknown functions. The expression pattern of nine genes with known functions involved in several abiotic stresses in other species was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) under cold (4 °C), salinity (NaCl), polyethylene glycol (PEG, MW 6000), and heavy metal treatments in leaves and stems at different time points (0, 24, 48, and 72 h). The expression patterns of the genes (TDF4, TDF7, TDF23, TDF45, TDF49, TDF50, TDF57, TDF91 and TDF92) that had direct or indirect relationships with cold, salinity, drought and heavy metal stress response were analyzed through qRT-PCR. The possible roles of these genes are discussed. This study suggests that the oligo-dT anchored cDNA-SCoT differential display method is a useful tool to serve as an initial step for characterizing transcriptional changes induced by abiotic stresses and provide gene information for further study and application in genetic improvement and breeding in mango. Copyright © 2014 Elsevier B.V. All rights reserved.

Visual-somatosensory integration and balance: evidence for psychophysical integrative differences in aging.

PubMed

Mahoney, Jeannette R; Holtzer, Roee; Verghese, Joe

2014-01-01

Research detailing multisensory integration (MSI) processes in aging and their association with clinically relevant outcomes is virtually non-existent. To our knowledge, the relationship between MSI and balance has not been well-established in aging. Given known alterations in unisensory processing with increasing age, the aims of the current study were to determine differential behavioral patterns of MSI in aging and investigate whether MSI was significantly associated with balance and fall-risk. Seventy healthy older adults (M = 75 years; 58% female) participated in the current study. Participants were instructed to make speeded responses to visual, somatosensory, and visual-somatosensory (VS) stimuli. Based on reaction times (RTs) to all stimuli, participants were classified into one of two groups (MSI or NO MSI), depending on their MSI RT benefit. Static balance was assessed using mean unipedal stance time. Overall, results revealed that RTs to VS stimuli were significantly shorter than those elicited to constituent unisensory conditions. Further, the current experimental design afforded differential patterns of multisensory processing, with 75% of the elderly sample demonstrating multisensory enhancements. Interestingly, 25% of older adults did not demonstrate multisensory RT facilitation; a finding that was attributed to extremely fast RTs overall and specifically in response to somatosensory inputs. Individuals in the NO MSI group maintained significantly better unipedal stance times and reported less falls, compared to elders in the MSI group. This study reveals the existence of differential patterns of multisensory processing in aging, while describing the clinical translational value of MSI enhancements in predicting balance and falls risk.

Visual-Somatosensory Integration and Balance: Evidence for Psychophysical Integrative Differences in Aging

PubMed Central

Mahoney, Jeannette R.; Holtzer, Roee; Verghese, Joe

2014-01-01

Research detailing multisensory integration (MSI) processes in aging and their association with clinically relevant outcomes is virtually non-existent. To our knowledge, the relationship between MSI and balance has not been well-established in aging. Given known alterations in unisensory processing with increasing age, the aims of the current study were to determine differential behavioral patterns of MSI in aging and investigate whether MSI was significantly associated with balance and fall-risk. Seventy healthy older adults (M = 75 years; 58% female) participated in the current study. Participants were instructed to make speeded responses to visual, somatosensory, and visual-somatosensory (VS) stimuli. Based on reaction times (RTs) to all stimuli, participants were classified into one of two groups (MSI or NO MSI), depending on their MSI RT benefit. Static balance was assessed using mean unipedal stance time. Overall, results revealed that RTs to VS stimuli were significantly shorter than those elicited to constituent unisensory conditions. Further, the current experimental design afforded differential patterns of multisensory processing, with 75% of the elderly sample demonstrating multisensory enhancements. Interestingly, 25% of older adults did not demonstrate multisensory RT facilitation; a finding that was attributed to extremely fast RTs overall and specifically in response to somatosensory inputs. Individuals in the NO MSI group maintained significantly better unipedal stance times and reported less falls, compared to elders in the MSI group. This study reveals the existence of differential patterns of multisensory processing in aging, while describing the clinical translational value of MSI enhancements in predicting balance and falls risk. PMID:25102664

Extensive transcriptional response associated with seasonal plasticity of butterfly wing patterns.

PubMed

Daniels, Emily V; Murad, Rabi; Mortazavi, Ali; Reed, Robert D

2014-12-01

In the eastern United States, the buckeye butterfly, Junonia coenia, shows seasonal wing colour plasticity where adults emerging in the spring are tan, while those emerging in the autumn are dark red. This variation can be artificially induced in laboratory colonies, thus making J. coenia a useful model system to examine the mechanistic basis of plasticity. To better understand the developmental basis of seasonal plasticity, we used RNA-seq to quantify transcription profiles associated with development of alternative seasonal wing morphs. Depending on the developmental stage, between 547 and 1420 transfrags were significantly differentially expressed between morphs. These extensive differences in gene expression stand in contrast to the much smaller numbers of differentially expressed transcripts identified in previous studies of genetic wing pattern variation in other species and suggest that environmentally induced phenotypic shifts arise from very broad systemic processes. Analyses of candidate endocrine and pigmentation transcripts revealed notable genes upregulated in the red morph, including several ecdysone-associated genes, and cinnabar, an ommochrome pigmentation gene implicated in colour pattern variation in other butterflies. We also found multiple melanin-related transcripts strongly upregulated in the red morph, including tan and yellow-family genes, leading us to speculate that dark red pigmentation in autumn J. coenia may involve nonommochrome pigments. While we identified several endocrine and pigmentation genes as obvious candidates for seasonal colour morph differentiation, we speculate that the majority of observed expression differences were due to thermal stress response. The buckeye transcriptome provides a basis for further developmental studies of phenotypic plasticity. © 2014 John Wiley & Sons Ltd.

Modelling effects of diquat under realistic exposure patterns in genetically differentiated populations of the gastropod Lymnaea stagnalis

PubMed Central

Ducrot, Virginie; Péry, Alexandre R. R.; Lagadic, Laurent

2010-01-01

Pesticide use leads to complex exposure and response patterns in non-target aquatic species, so that the analysis of data from standard toxicity tests may result in unrealistic risk forecasts. Developing models that are able to capture such complexity from toxicity test data is thus a crucial issue for pesticide risk assessment. In this study, freshwater snails from two genetically differentiated populations of Lymnaea stagnalis were exposed to repeated acute applications of environmentally realistic concentrations of the herbicide diquat, from the embryo to the adult stage. Hatching rate, embryonic development duration, juvenile mortality, feeding rate and age at first spawning were investigated during both exposure and recovery periods. Effects of diquat on mortality were analysed using a threshold hazard model accounting for time-varying herbicide concentrations. All endpoints were significantly impaired at diquat environmental concentrations in both populations. Snail evolutionary history had no significant impact on their sensitivity and responsiveness to diquat, whereas food acted as a modulating factor of toxicant-induced mortality. The time course of effects was adequately described by the model, which thus appears suitable to analyse long-term effects of complex exposure patterns based upon full life cycle experiment data. Obtained model outputs (e.g. no-effect concentrations) could be directly used for chemical risk assessment. PMID:20921047

Modelling effects of diquat under realistic exposure patterns in genetically differentiated populations of the gastropod Lymnaea stagnalis.

PubMed

Ducrot, Virginie; Péry, Alexandre R R; Lagadic, Laurent

2010-11-12

Pesticide use leads to complex exposure and response patterns in non-target aquatic species, so that the analysis of data from standard toxicity tests may result in unrealistic risk forecasts. Developing models that are able to capture such complexity from toxicity test data is thus a crucial issue for pesticide risk assessment. In this study, freshwater snails from two genetically differentiated populations of Lymnaea stagnalis were exposed to repeated acute applications of environmentally realistic concentrations of the herbicide diquat, from the embryo to the adult stage. Hatching rate, embryonic development duration, juvenile mortality, feeding rate and age at first spawning were investigated during both exposure and recovery periods. Effects of diquat on mortality were analysed using a threshold hazard model accounting for time-varying herbicide concentrations. All endpoints were significantly impaired at diquat environmental concentrations in both populations. Snail evolutionary history had no significant impact on their sensitivity and responsiveness to diquat, whereas food acted as a modulating factor of toxicant-induced mortality. The time course of effects was adequately described by the model, which thus appears suitable to analyse long-term effects of complex exposure patterns based upon full life cycle experiment data. Obtained model outputs (e.g. no-effect concentrations) could be directly used for chemical risk assessment.

Circadian Rhythms Regulate Amelogenesis

PubMed Central

Zheng, Li; Seon, Yoon Ji; Mourão, Marcio A.; Schnell, Santiago; Kim, Doohak; Harada, Hidemitsu; Papagerakis, Silvana; Papagerakis, Petros

2013-01-01

Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24h) intervals both at RNA and protein levels. This study also reveals that two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stage of amelogenesis might be under circadian control. Changes in clock genes expression patterns might result in significant alterations of enamel apposition and mineralization. PMID:23486183

Tumor Cell Plasticity in Uveal Melanoma

PubMed Central

Folberg, Robert; Arbieva, Zarema; Moses, Jonas; Hayee, Amin; Sandal, Tone; Kadkol, ShriHari; Lin, Amy Y.; Valyi-Nagy, Klara; Setty, Suman; Leach, Lu; Chévez-Barrios, Patricia; Larsen, Peter; Majumdar, Dibyen; Pe’er, Jacob; Maniotis, Andrew J.

2006-01-01

The histological detection of laminin-rich vasculogenic mimicry patterns in human primary uveal melanomas is associated with death from metastases. We therefore hypothesized that highly invasive uveal melanoma cells forming vasculogenic mimicry patterns after exposure to a laminin-rich three-dimensional microenvironment would differentially express genes associated with invasive and metastatic behavior. However, we discovered that genes associated with differentiation (GDF15 and ATF3) and suppression of proliferation (CDKNa1/p21) were up-regulated in highly invasive uveal melanoma cells forming vasculogenic mimicry patterns, and genes associated with promotion of invasive and metastatic behavior such as CD44, CCNE2 (cyclin E2), THBS1 (thrombospondin 1), and CSPG2 (chondroitin sulfate proteoglycan; versican) were down-regulated. After forming vasculogenic mimicry patterns, uveal melanoma cells invaded only short distances, failed to replicate, and changed morphologically from the invasive epithelioid to the indolent spindle A phenotype. In human tissue samples, uveal melanoma cells within vasculogenic mimicry patterns assumed the spindle A morphology, and the expression of Ki67 was significantly reduced in adjacent melanoma cells. Thus, the generation of vasculogenic mimicry patterns is accompanied by dampening of the invasive and metastatic uveal melanoma genotype and phenotype and underscores the plasticity of these cells in response to cues from the microenvironment. PMID:17003493

Caregiver Appraisals of Functional Dependence in Individuals With Dementia and Associated Caregiver Upset: Psychometric Properties of a New Scale and Response Patterns by Caregiver and Care Recipient Characteristics

PubMed Central

GITLIN, LAURA N.; ROTH, DAVID L.; BURGIO, LOUIS D.; LOEWENSTEIN, DAVID A.; WINTER, LARAINE; NICHOLS, LINDA; ARGÜELLES, SOLEDAD; CORCORAN, MARY; BURNS, ROBERT; MARTINDALE, JENNIFER

2008-01-01

Objective To evaluate psychometric properties and response patterns of the Caregiver Assessment of Function and Upset (CAFU), a 15-item multidimensional measure of dependence in dementia patients and caregiver reaction. Method 640 families were administered the CAFU (53% White, 43% African American, and 4% mixed race and ethnicity). We created a random split of the sample and conducted exploratory factor analyses on Sample 1 and confirmatory factor analyses on Sample 2. Convergent and discriminant validity were evaluated using Spearman rank correlation coefficients. Results A two-factor structure for functional items was derived, and excellent factorial validity was obtained. Convergent and discriminant validity were obtained for function and upset measures. Differential response patterns for dependence and caregiver upset were found for caregiver race, relationship, and care recipient gender but not for caregiver gender. Discussion The CAFU is easily administered, reliable, and valid for evaluating appraisals of dependencies and upsetting care areas. PMID:15750049

Proteome and Secretome Analysis Reveals Differential Post-transcriptional Regulation of Toll-like Receptor Responses*

PubMed Central

Koppenol-Raab, Marijke; Sjoelund, Virginie; Manes, Nathan P.; Gottschalk, Rachel A.; Dutta, Bhaskar; Benet, Zachary L.; Fraser, Iain D. C.

2017-01-01

The innate immune system is the organism's first line of defense against pathogens. Pattern recognition receptors (PRRs) are responsible for sensing the presence of pathogen-associated molecules. The prototypic PRRs, the membrane-bound receptors of the Toll-like receptor (TLR) family, recognize pathogen-associated molecular patterns (PAMPs) and initiate an innate immune response through signaling pathways that depend on the adaptor molecules MyD88 and TRIF. Deciphering the differences in the complex signaling events that lead to pathogen recognition and initiation of the correct response remains challenging. Here we report the discovery of temporal changes in the protein signaling components involved in innate immunity. Using an integrated strategy combining unbiased proteomics, transcriptomics and macrophage stimulations with three different PAMPs, we identified differences in signaling between individual TLRs and revealed specifics of pathway regulation at the protein level. PMID:28235783

"Contrasting patterns of selection at Pinus pinaster Ait. Drought stress candidate genes as revealed by genetic differentiation analyses".

PubMed

Eveno, Emmanuelle; Collada, Carmen; Guevara, M Angeles; Léger, Valérie; Soto, Alvaro; Díaz, Luis; Léger, Patrick; González-Martínez, Santiago C; Cervera, M Teresa; Plomion, Christophe; Garnier-Géré, Pauline H

2008-02-01

The importance of natural selection for shaping adaptive trait differentiation among natural populations of allogamous tree species has long been recognized. Determining the molecular basis of local adaptation remains largely unresolved, and the respective roles of selection and demography in shaping population structure are actively debated. Using a multilocus scan that aims to detect outliers from simulated neutral expectations, we analyzed patterns of nucleotide diversity and genetic differentiation at 11 polymorphic candidate genes for drought stress tolerance in phenotypically contrasted Pinus pinaster Ait. populations across its geographical range. We compared 3 coalescent-based methods: 2 frequentist-like, including 1 approach specifically developed for biallelic single nucleotide polymorphisms (SNPs) here and 1 Bayesian. Five genes showed outlier patterns that were robust across methods at the haplotype level for 2 of them. Two genes presented higher F(ST) values than expected (PR-AGP4 and erd3), suggesting that they could have been affected by the action of diversifying selection among populations. In contrast, 3 genes presented lower F(ST) values than expected (dhn-1, dhn2, and lp3-1), which could represent signatures of homogenizing selection among populations. A smaller proportion of outliers were detected at the SNP level suggesting the potential functional significance of particular combinations of sites in drought-response candidate genes. The Bayesian method appeared robust to low sample sizes, flexible to assumptions regarding migration rates, and powerful for detecting selection at the haplotype level, but the frequentist-like method adapted to SNPs was more efficient for the identification of outlier SNPs showing low differentiation. Population-specific effects estimated in the Bayesian method also revealed populations with lower immigration rates, which could have led to favorable situations for local adaptation. Outlier patterns are discussed in relation to the different genes' putative involvement in drought tolerance responses, from published results in transcriptomics and association mapping in P. pinaster and other related species. These genes clearly constitute relevant candidates for future association studies in P. pinaster.

The role and functions of Clinical Nurse Consultants, an Australian advanced practice role: a descriptive exploratory cohort study.

PubMed

Baldwin, Richard; Duffield, Christine Margaret; Fry, Margaret; Roche, Michael; Stasa, Helen; Solman, Annette

2013-03-01

The NSW Health Policy Directive (NSW Department of Health, 2000) lists clinical service and consultancy; clinical leadership; research; education; clinical services planning and management as the five domains of practice for nurses appointed as Clinical Nurse Consultants (CNCs), an Australian advanced practice nurse (APN) role. However, there is no clear definition of what is meant by advanced practice in the Australian nursing context. Nowhere is this more evident than in differentiating between the roles of Clinical Nurse Consultants (CNCs) and Nurse Practitioners (NP) in NSW. To date, limited empirical research has been done to characterise or delineate CNC role activity and responsibility. To investigate (i) the nature of CNC roles, activities and responsibilities, (ii) differentiate between CNCs by their work patterns and activities, and (iii) empirically conceptualize and differentiate ways CNCs practice in terms of an APN typology. The study sample was 56 CNCs at one tertiary level public hospital in Australia. A descriptive exploratory cohort study was conducted to explore CNC role characteristics and patterns of activity. Data were triangulated using an online survey, a follow-up survey, and semi-structured interviews. The data were analysed using descriptive statistics to examine differences between CNC work patterns and role activities. The survey data and the individual reports were thematically analysed to investigate for difference across the population of CNCs. Interpretation of survey and interview data led to an analyst-developed CNC typology of four CNC categories based on the work patterns and activities of Sole Practitioner, Clinic Coordinator, Clinical Team Coordinator and Clinical Leader. The typology was based on the themes interprofessional, role focus, clinical focus and setting as these themes distinguished and differentiated CNC roles. The study provides evidence of great diversity and prioritization within CNC roles. The CNC typology identified in this study is similar to the categorisation of the roles of APNs reported by other researchers. With further testing, the CNC typology could be useful to service managers and policy makers in making decision on the category of CNC required for a position and may also be able to be applied to other APN roles. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hypoxia Stress Modifies Na+/K+-ATPase, H+/K+-ATPase, Na+/NH4+-ATPase, and nkaα1 Isoform Expression in the Brain of Immune-Challenged Air-Breathing Fish

PubMed Central

Peter, MC Subhash; Simi, Satheesan

2017-01-01

Fishes are equipped to sense stressful stimuli and are able to respond to environmental stressor such as hypoxia with varying pattern of stress response. The functional attributes of brain to hypoxia stress in relation to ion transport and its interaction during immune challenge have not yet delineated in fish. We, therefore, explored the pattern of ion transporter functions and messenger RNA (mRNA) expression of α1-subunit isoforms of Na+/K+-ATPase (NKA) in the brain segments, namely, prosencephalon (PC), mesencephalon (MC), and metencephalon (MeC) in an obligate air-breathing fish exposed either to hypoxia stress (30 minutes forced immersion in water) or challenged with zymosan treatment (25-200 ng g−1 for 24 hours) or both. Zymosan that produced nonspecific immune responses evoked differential regulation of NKA, H+/K+-ATPase (HKA), and Na+/NH4+-ATPase (NNA) in the varied brain segments. On the contrary, hypoxia stress that demanded activation of NKA in PC and MeC showed a reversed NKA activity pattern in MeC of immune-challenged fish. A compromised HKA and NNA regulation during hypoxia stress was found in immune-challenged fish, indicating the role of these brain ion transporters to hypoxia stress and immune challenges. The differential mRNA expression of α1-subunit isoforms of NKA, nkaα1a, nkaα1b, and nkaα1c, in hypoxia-stressed brain showed a shift in its expression pattern during hypoxia stress-immune interaction in PC and MC. Evidence is thus presented for the first time that ion transporters such as HKA and NNA along with NKA act as functional brain markers which respond differentially to both hypoxia stress and immune challenges. Taken together, the data further provide evidence for a differential Na+, K+, H+, and NH4+ ion signaling that exists in brain neuronal clusters during hypoxia stress-immune interaction as a result of modified regulations of NKA, HKA, and NNA transporter functions and nkaα1 isoform regulation. PMID:29238219

Hypoxia Stress Modifies Na+/K+-ATPase, H+/K+-ATPase, [Formula: see text], and nkaα1 Isoform Expression in the Brain of Immune-Challenged Air-Breathing Fish.

PubMed

Peter, Mc Subhash; Simi, Satheesan

2017-01-01

Fishes are equipped to sense stressful stimuli and are able to respond to environmental stressor such as hypoxia with varying pattern of stress response. The functional attributes of brain to hypoxia stress in relation to ion transport and its interaction during immune challenge have not yet delineated in fish. We, therefore, explored the pattern of ion transporter functions and messenger RNA (mRNA) expression of α1-subunit isoforms of Na + /K + -ATPase (NKA) in the brain segments, namely, prosencephalon (PC), mesencephalon (MC), and metencephalon (MeC) in an obligate air-breathing fish exposed either to hypoxia stress (30 minutes forced immersion in water) or challenged with zymosan treatment (25-200 ng g -1 for 24 hours) or both. Zymosan that produced nonspecific immune responses evoked differential regulation of NKA, H + /K + -ATPase (HKA), and [Formula: see text] (NNA) in the varied brain segments. On the contrary, hypoxia stress that demanded activation of NKA in PC and MeC showed a reversed NKA activity pattern in MeC of immune-challenged fish. A compromised HKA and NNA regulation during hypoxia stress was found in immune-challenged fish, indicating the role of these brain ion transporters to hypoxia stress and immune challenges. The differential mRNA expression of α1-subunit isoforms of NKA, nkaα1a , nkaα1b , and nkaα1c , in hypoxia-stressed brain showed a shift in its expression pattern during hypoxia stress-immune interaction in PC and MC. Evidence is thus presented for the first time that ion transporters such as HKA and NNA along with NKA act as functional brain markers which respond differentially to both hypoxia stress and immune challenges. Taken together, the data further provide evidence for a differential Na + , K + , H + , and [Formula: see text] ion signaling that exists in brain neuronal clusters during hypoxia stress-immune interaction as a result of modified regulations of NKA, HKA, and NNA transporter functions and nkaα1 isoform regulation.

Fungal and host transcriptome analysis of pH-regulated genes during colonization of apple fruits by Penicillium expansum.

PubMed

Barad, Shiri; Sela, Noa; Kumar, Dilip; Kumar-Dubey, Amit; Glam-Matana, Nofar; Sherman, Amir; Prusky, Dov

2016-05-04

Penicillium expansum is a destructive phytopathogen that causes decay in deciduous fruits during postharvest handling and storage. During colonization the fungus secretes D-gluconic acid (GLA), which modulates environmental pH and regulates mycotoxin accumulation in colonized tissue. Till now no transcriptomic analysis has addressed the specific contribution of the pathogen's pH regulation to the P. expansum colonization process. For this purpose total RNA from the leading edge of P. expansum-colonized apple tissue of cv. 'Golden Delicious' and from fungal cultures grown under pH 4 or 7 were sequenced and their gene expression patterns were compared. We present a large-scale analysis of the transcriptome data of P. expansum and apple response to fungal colonization. The fungal analysis revealed nine different clusters of gene expression patterns that were divided among three major groups in which the colonized tissue showed, respectively: (i) differing transcript expression patterns between mycelial growth at pH 4 and pH 7; (ii) similar transcript expression patterns of mycelial growth at pH 4; and (iii) similar transcript expression patterns of mycelial growth at pH 7. Each group was functionally characterized in order to decipher genes that are important for pH regulation and also for colonization of apple fruits by Penicillium. Furthermore, comparison of gene expression of healthy apple tissue with that of colonized tissue showed that differentially expressed genes revealed up-regulation of the jasmonic acid and mevalonate pathways, and also down-regulation of the glycogen and starch biosynthesis pathways. Overall, we identified important genes and functionalities of P. expansum that were controlled by the environmental pH. Differential expression patterns of genes belonging to the same gene family suggest that genes were selectively activated according to their optimal environmental conditions (pH, in vitro or in vivo) to enable the fungus to cope with varying conditions and to make optimal use of available enzymes. Comparison between the activation of the colonized host's gene responses by alkalizing Colletotrichum gloeosporioides and acidifying P. expansum pathogens indicated similar gene response patterns, but stronger responses to P. expansum, suggesting the importance of acidification by P. expansum as a factor in its increased aggressiveness.

An Exercise to Estimate Differential Gene Expression in Human Cells

ERIC Educational Resources Information Center

Chaudhry, M. Ahmad

2006-01-01

The expression of genes in cells of various tissue types varies considerably and is correlated with the function of a particular organ. The pattern of gene expression changes in diseased tissues, in response to therapy or infection and exposure to environmental mutagens, chemicals, ultraviolet light, and ionizing radiation. To better understand…

Elucidation of miRNAs-Mediated Responses to Low Nitrogen Stress by Deep Sequencing of Two Soybean Genotypes

PubMed Central

Wang, Yejian; Zhang, Chanjuan; Hao, Qinnan; Sha, Aihua; Zhou, Rong; Zhou, Xinan; Yuan, Longping

2013-01-01

Nitrogen (N) is a major limiting factor in crop production, and plant adaptive responses to low N are involved in many post-transcriptional regulation. Recent studies indicate that miRNAs play important roles in adaptive responses. However, miRNAs in soybean adaptive responses to N limitation have been not reported. We constructed sixteen libraries to identify low N-responsive miRNAs on a genome-wide scale using samples from 2 different genotypes (low N sensitive and low N tolerant) subjected to various periods of low nitrogen stress. Using high-throughput sequencing technology (Illumina-Solexa), we identified 362 known miRNAs variants belonging to 158 families and 90 new miRNAs belonging to 55 families. Among these known miRNAs variants, almost 50% were not different from annotated miRNAs in miRBase. Analyses of their expression patterns showed 150 known miRNAs variants as well as 2 novel miRNAs with differential expressions. These differentially expressed miRNAs between the two soybean genotypes were compared and classified into three groups based on their expression patterns. Predicted targets of these miRNAs were involved in various metabolic and regulatory pathways such as protein degradation, carbohydrate metabolism, hormone signaling pathway, and cellular transport. These findings suggest that miRNAs play important roles in soybean response to low N and contribute to the understanding of the genetic basis of differences in adaptive responses to N limitation between the two soybean genotypes. Our study provides basis for expounding the complex gene regulatory network of these miRNAs. PMID:23861762

Differentiation of Effector CD4 T Cell Populations*

PubMed Central

Zhu, Jinfang; Yamane, Hidehiro; Paul, William E.

2012-01-01

CD4 T cells play critical roles in mediating adaptive immunity to a variety of pathogens. They are also involved in autoimmunity, asthma, and allergic responses as well as in tumor immunity. During TCR activation in a particular cytokine milieu, naive CD4 T cells may differentiate into one of several lineages of T helper (Th) cells, including Th1, Th2, Th17, and iTreg, as defined by their pattern of cytokine production and function. In this review, we summarize the discovery, functions, and relationships among Th cells; the cytokine and signaling requirements for their development; the networks of transcription factors involved in their differentiation; the epigenetic regulation of their key cytokines and transcription factors; and human diseases involving defective CD4 T cell differentiation. PMID:20192806

Racism, society, and disease: an exploration of the social and biological mechanisms of differential mortality.

PubMed

Cooper, R; Steinhauer, M; Miller, W; David, R; Schatzkin, A

1981-01-01

Racial differentials in mortality provide important insight into the nature of mass disease in capitalist society. Not only are the differentials sizable in magnitude, they are consistent for multiple causes of death and appear to evolve in response to social development. The relationships among social factors and the biological and physical agents of disease can be identified through racial contrasts and a pattern of causation which applies to both the minority and majority populations described. Furthermore, the impact of exploitation as the primary disease-mediating factor under capitalist social relations can be estimated. This paper attempts to combine an analysis of bio-medical mechanisms with Marxist social theory in a comprehensive framework for the study of the social origins of racial differentials.

Generation of Hepatocytes from Pluripotent Stem Cells for Drug Screening and Developmental Modeling.

PubMed

Gieseck, Richard L; Vallier, Ludovic; Hannan, Nicholas R F

2015-01-01

Hepatocytes produced from the differentiation of human pluripotent stem cells can be used to study human development and liver disease, to investigate the toxicological response of novel drug candidates, and as an alternative source of primary cells for transplantation therapies. Here, we describe a method to produce hepatocytes by differentiating human pluripotent stem cells into definitive endoderm, patterning definitive endoderm into anterior definitive endoderm, specifying anterior definitive endoderm into hepatic endoderm, and differentiating hepatic endoderm into immature hepatocytes. These cells are further matured in either two-dimensional or three-dimensional culture conditions to produce cells capable of metabolizing xenobiotics and generating liver-specific proteins, such as albumin and alpha 1 antitrypsin.

Do Processing Patterns of Strengths and Weaknesses Predict Differential Treatment Response?

PubMed

Miciak, Jeremy; Williams, Jacob L; Taylor, W Pat; Cirino, Paul T; Fletcher, Jack M; Vaughn, Sharon

2016-08-01

No previous empirical study has investigated whether the LD identification decisions of proposed methods to operationalize processing strengths and weaknesses (PSW) approaches for LD identification are associated with differential treatment response. We investigated whether the identification decisions of the concordance/discordance model (C/DM; Hale & Fiorello, 2004) and Cross Battery Assessment approach (XBA method; Flanagan, Ortiz, & Alfonso, 2007) were consistent and whether they predicted intervention response beyond that accounted for by pretest performance on measures of reading. Psychoeducational assessments were administered at pretest to 203 4 th graders with low reading comprehension and individual results were utilized to identify students who met LD criteria according to the C/DM and XBA methods and students who did not. Resulting group status permitted an investigation of agreement for identification methods and whether group status at pretest (LD or not LD) was associated with differential treatment response to an intensive reading intervention. The LD identification decisions of the XBA and C/DM demonstrated poor agreement with one another (κ = -.10). Comparisons of posttest performance for students who met LD criteria and those who did not meet were largely null, with small effect sizes across all measures. LD status, as identified through the C/DM and XBA approaches, was not associated with differential treatment response and did not contribute educationally meaningful information about how students would respond to intensive reading intervention. These results do not support the value of cognitive assessment utilized in this way as part of the LD identification process.

Differential expression profiles and pathways of genes in sugarcane leaf at elongation stage in response to drought stress

PubMed Central

Li, Changning; Nong, Qian; Solanki, Manoj Kumar; Liang, Qiang; Xie, Jinlan; Liu, Xiaoyan; Li, Yijie; Wang, Weizan; Yang, Litao; Li, Yangrui

2016-01-01

Water stress causes considerable yield losses in sugarcane. To investigate differentially expressed genes under water stress, a pot experiment was performed with the sugarcane variety GT21 at three water-deficit levels (mild, moderate, and severe) during the elongation stage and gene expression was analyzed using microarray technology. Physiological parameters of sugarcane showed significant alterations in response to drought stress. Based on the expression profile of 15,593 sugarcane genes, 1,501 (9.6%) genes were differentially expressed under different water-level treatments; 821 genes were upregulated and 680 genes were downregulated. A gene similarity analysis showed that approximately 62.6% of the differentially expressed genes shared homology with functional proteins. In a Gene Ontology (GO) analysis, 901 differentially expressed genes were assigned to 36 GO categories. Moreover, 325 differentially expressed genes were classified into 101 pathway categories involved in various processes, such as the biosynthesis of secondary metabolites, ribosomes, carbon metabolism, etc. In addition, some unannotated genes were detected; these may provide a basis for studies of water-deficit tolerance. The reliability of the observed expression patterns was confirmed by RT-PCR. The results of this study may help identify useful genes for improving drought tolerance in sugarcane. PMID:27170459

Morphological diversity of the avian foot is related with the pattern of msx gene expression in the developing autopod.

PubMed

Gañan, Y; Macias, D; Basco, R D; Merino, R; Hurle, J M

1998-04-01

The formation of the digits in amniota embryos is accompanied by apoptotic cell death of the interdigital mesoderm triggered through BMP signaling. Differences in the intensity of this apoptotic process account for the establishment of the different morphological types of feet observed in amniota (i.e., free-digits, webbed digits, lobulated digits). The molecular basis accounting for the differential pattern of interdigital cell death remains uncertain since the reduction of cell death in species with webbed digits is not accompanied by a parallel reduction in the pattern of expression of bmp genes in the interdigital regions. In this study we show that the duck interdigital web mesoderm exhibits an attenuated response to both BMP-induced apoptosis and TGFbeta-induced chondrogenesis in comparison with species with free digits. The attenuated response to these signals is accompanied by a reduced pattern of expression of msx-1 and msx-2 genes. Local application of FGF in the duck interdigit expands the domain of msx-2 expression but not the domain of msx-1 expression. This change in the expression of msx-2 is followed by a parallel increase in spontaneous and exogenous BMP-induced interdigital cell death, while the chondrogenic response to TGFbetas is unchanged. The regression of AER, as deduced by the pattern of extinction of fgf-8 expression, takes place in a similar fashion in the chick and duck regardless of the differences in interdigital cell death and msx gene expression. Implantation of BMP-beads in the distal limb mesoderm induces AER regression in both the chick and duck. This finding suggests an additional role for BMPs in the physiological regression of the AER. It is proposed that the formation of webbed vs free-digit feet in amniota results from a premature differentiation of the interdigital mesoderm into connective tissue caused by a reduced expression of msx genes in the developing autopod. Copyright 1998 Academic Press.

Gene expression plasticity in response to salinity acclimation in threespine stickleback ecotypes from different salinity habitats.

PubMed

Gibbons, Taylor C; Metzger, David C H; Healy, Timothy M; Schulte, Patricia M

2017-05-01

Phenotypic plasticity is thought to facilitate the colonization of novel environments and shape the direction of evolution in colonizing populations. However, the relative prevalence of various predicted patterns of changes in phenotypic plasticity following colonization remains unclear. Here, we use a whole-transcriptome approach to characterize patterns of gene expression plasticity in the gills of a freshwater-adapted and a saltwater-adapted ecotype of threespine stickleback (Gasterosteus aculeatus) exposed to a range of salinities. The response of the gill transcriptome to environmental salinity had a large shared component common to both ecotypes (2159 genes) with significant enrichment of genes involved in transmembrane ion transport and the restructuring of the gill epithelium. This transcriptional response to freshwater acclimation is induced at salinities below two parts per thousand. There was also differentiation in gene expression patterns between ecotypes (2515 genes), particularly in processes important for changes in the gill structure and permeability. Only 508 genes that differed between ecotypes also responded to salinity and no specific processes were enriched among this gene set, and an even smaller number (87 genes) showed evidence of changes in the extent of the response to salinity acclimation between ecotypes. No pattern of relative expression dominated among these genes, suggesting that neither gains nor losses of plasticity dominated the changes in expression patterns between the ecotypes. These data demonstrate that multiple patterns of changes in gene expression plasticity can occur following colonization of novel habitats. © 2017 John Wiley & Sons Ltd.

Role of Integrin in Mechanical Loading of Osteoblasts

NASA Technical Reports Server (NTRS)

Globus, Ruth; Demsky, Caroline

2000-01-01

Mechanical forces generated by gravity, weightbearing, and muscle contraction play a key role in the genesis and maintenance of skeletal structure. The molecular mechanisms that mediate changes in osteoblast activity in response to altered patterns of skeletal loading are not known, and a better understanding of these processes may be essential for developing effective treatment strategies to prevent disuse osteoporosis. We have elucidated specific integrin/ECM (extracellular matrix) interactions that are required for osteoblast differentiation and survival and have developed a useful loading system to further explore the molecular basis of mechano-sensitivity of osteoblasts. The long term goal of our collaborative research is to understand how the ECM and cell adhesion proteins and integrins interaction to mediate the response of osteoblasts and their progenitors to mechanical loading. We suggest that integrin/ECM interactions are crucial for basic cellular processes, including differentiation and survival, as well as to participate in detecting and mediating cellular responses to mechanical stimuli.

Comparative Transcriptome Analysis of the Necrotrophic Fungus Ascochyta rabiei during Oxidative Stress: Insight for Fungal Survival in the Host Plant

PubMed Central

Singh, Kunal; Nizam, Shadab; Sinha, Manisha; Verma, Praveen K.

2012-01-01

Localized cell death, known as the hypersensitive response (HR), is an important defense mechanism for neutralizing phytopathogens. The hallmark of the HR is an oxidative burst produced by the host plant. We aimed to identify genes of the necrotrophic chickpea blight fungus Ascochyta rabiei that are involved in counteracting oxidative stress. A subtractive cDNA library was constructed after menadione treatment, which resulted in the isolation of 128 unigenes. A reverse northern blot was used to compare transcript profiles after H2O2, menadione and sodium nitroprusside treatments. A total of 70 unigenes were found to be upregulated by more than two-fold following menadione treatment at different time intervals. A large number of genes not previously associated with oxidative stress were identified, along with many stress-responsive genes. Differential expression patterns of several genes were validated by quantitative real-time PCR (qRT-PCR) and northern blotting. In planta qRT-PCR of several selected genes also showed differential expression patterns during infection and disease progression. These data shed light on the molecular responses of the phytopathogen A. rabiei to overcome oxidative and nitrosative stresses and advance the understanding of necrotrophic fungal pathogen survival mechanisms. PMID:22427966

Divergent cytosine DNA methylation patterns in single-cell, soybean root hairs.

PubMed

Hossain, Md Shakhawat; Kawakatsu, Taiji; Kim, Kyung Do; Zhang, Ning; Nguyen, Cuong T; Khan, Saad M; Batek, Josef M; Joshi, Trupti; Schmutz, Jeremy; Grimwood, Jane; Schmitz, Robert J; Xu, Dong; Jackson, Scott A; Ecker, Joseph R; Stacey, Gary

2017-04-01

Chromatin modifications, such as cytosine methylation of DNA, play a significant role in mediating gene expression in plants, which affects growth, development, and cell differentiation. As root hairs are single-cell extensions of the root epidermis and the primary organs for water uptake and nutrients, we sought to use root hairs as a single-cell model system to measure the impact of environmental stress. We measured changes in cytosine DNA methylation in single-cell root hairs as compared with multicellular stripped roots, as well as in response to heat stress. Differentially methylated regions (DMRs) in each methylation context showed very distinct methylation patterns between cell types and in response to heat stress. Intriguingly, at normal temperature, root hairs were more hypermethylated than were stripped roots. However, in response to heat stress, both root hairs and stripped roots showed hypomethylation in each context, especially in the CHH context. Moreover, expression analysis of mRNA from similar tissues and treatments identified some associations between DMRs, genes and transposons. Taken together, the data indicate that changes in DNA methylation are directly or indirectly associated with expression of genes and transposons within the context of either specific tissues/cells or stress (heat). © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Cellular Interactions and Immune Response of Spherical Nucleic Acid (SNA) Nanoconjugates

NASA Astrophysics Data System (ADS)

Massich, Matthew David

Spherical nucleic acid (SNA) nanoconjugates consist of a densely packed monolayer shell of highly-oriented oligonucleotides covalently bound to a gold nanoparticle core. The nanoconjugates exhibit several important qualities, which make them useful for various biological applications, such as antisense gene regulation strategies and the intracellular detection of biomolecules. The focus of this thesis was to characterize the nanoconjugates interaction with cultured cells and specifically the immune response to their intracellular presence. The immune response of macrophage cells to internalized nanoconjugates was studied, and due to the dense functionalization of oligonucleotides on the surface of the nanoparticle and the resulting high localized salt concentration the innate immune response to the nanoconjugates is ˜25-fold less when compared to a lipoplex carrying the same sequence. Additionally, genome-wide expression profiling was used to study the biological response of cultured cells to the nanoconjugates. The biological response of HeLa cells to gold nanoparticles stabilized by weakly bound ligands was significant, yet when these same nanoparticles were stably functionalized with covalently attached oligonucleotides the cells showed no measurable response. In human keratinocytes, the oligonucleotide sequences caused 427 genes to be differentially expressed when complexed with Dharmafect, but when the oligonucleotides were conjugated to nanoparticles only 7 genes were differentially expressed. Beyond characterizing the cellular interactions and immune response of the nanoconjugates, the optimal length of siRNA (from 19--34 base pairs) that induces the most gene knockdown while maintaining limited immune activation was determined to be 24 base pairs. Further, the SNAs were shown to be useful as a potential antiviral gene therapy by demonstrating approximately 50% knockdown of the Ebola VP35 gene. Lastly, a scanning probe-enabled method was used to rapidly create nanoscale fibronectin patterns over large areas with a range of feature sizes, thereby opening the field of nanocombinatorics. This allowed the investigation of the relationship between fibronectin feature size and stem cell fate. MSCs cultured on nanoscale fibronectin features directed differentiation toward osteogenesis to a greater extent than cells grown on both microscale features and cells grown on non-patterned fibronectin substrates with osteogenic inducing media, demonstrating a new method for controlling stem cell fate.

The Response of Human Macrophages to β-Glucans Depends on the Inflammatory Milieu

PubMed Central

Montero, Olimpio; Hugo, Etzel; Rodríguez, Mario; Domingo, Esther; Alonso, Sara

2013-01-01

Background β-glucans are fungal cell wall components that bind to the C-type lectin-like receptor dectin-1. Polymorphisms of dectin-1 gene are associated with susceptibility to invasive fungal infection and medically refractory ulcerative colitis. The purpose of this study has been addressing the response of human macrophages to β-glucans under different conditions mimicking the composition of the inflammatory milieu in view of the wide plasticity and large range of phenotypical changes showed by these cells, and the relevant role of dectin-1 in several pathophysiological conditions. Principal Findings Serum-differentiated macrophages stimulated with β-glucans showed a low production of TNFα and IL-1β, a high production of IL-6 and IL-23, and a delayed induction of cyclooxygenase-2 and PGE2 biosynthesis that resembled the responses elicited by crystals and those produced when phagosomal degradation of the phagocytic cargo increases ligand access to intracellular pattern recognition receptors. Priming with a low concentration of LPS produced a rapid induction of cyclooxygenase-2 and a synergistic release of PGE2. When the differentiation of the macrophages was carried out in the presence of M-CSF, an increased expression of dectin-1 B isoform was observed. In addition, this treatment made the cells capable to release arachidonic acid in response to β-glucan. Conclusions These results indicate that the macrophage response to fungal β-glucans is strongly influenced by cytokines and microbial-derived factors that are usual components of the inflammatory milieu. These responses can be sorted into three main patterns i) an elementary response dependent on phagosomal processing of pathogen-associated molecular patterns and/or receptor-independent, direct membrane binding linked to the immunoreceptor tyrosine-based activation motif-bearing transmembrane adaptor DNAX-activating protein 12, ii) a response primed by TLR4-dependent signals, and iii) a response dependent on M-CSF and dectin-1 B isoform expression that mainly signals through the dectin-1 B/spleen tyrosine kinase/cytosolic phospholipase A2 route. PMID:23637950

TACTILE RESPONSIVENESS PATTERNS AND THEIR ASSOCIATION WITH CORE FEATURES IN AUTISM SPECTRUM DISORDERS

PubMed Central

Foss-Feig, Jennifer H.; Heacock, Jessica L.; Cascio, Carissa J.

2011-01-01

Autism spectrum disorders (ASD) are often associated with aberrant responses to sensory stimuli, which are thought to contribute to the social, communication, and repetitive behavior deficits that define ASD. However, there are few studies that separate aberrant sensory responses by individual sensory modality to assess modality-specific associations between sensory features and core symptoms. Differences in response to tactile stimuli are prevalent in ASD, and tactile contact early in infancy is a foundation for the development of social and communication skills affected by ASD. We assessed the association between three aberrant patterns of tactile responsiveness (hyper-responsiveness, hypo-responsiveness, sensory seeking) and core symptoms of ASD. Both sensory and core features were measured with converging methods including both parent-report and direct observation. Our results demonstrate that for the tactile modality, sensory hypo-responsiveness correlates strongly with increased social and communication impairments, and to a lesser degree, repetitive behaviors. Sensory seeking was found to correlate strongly with social impairment, nonverbal communication impairment, and repetitive behaviors. Surprisingly, tactile hyper-responsiveness did not significantly correlate with any core features of ASD. This differential association between specific tactile processing patterns and core features provides an important step in defining the significance of sensory symptoms in ASD, and may be useful in the development of sensory–based approaches for early detection and intervention. PMID:22059092

In Vivo Pattern Classification of Ingestive Behavior in Ruminants Using FBG Sensors and Machine Learning.

PubMed

Pegorini, Vinicius; Karam, Leandro Zen; Pitta, Christiano Santos Rocha; Cardoso, Rafael; da Silva, Jean Carlos Cardozo; Kalinowski, Hypolito José; Ribeiro, Richardson; Bertotti, Fábio Luiz; Assmann, Tangriani Simioni

2015-11-11

Pattern classification of ingestive behavior in grazing animals has extreme importance in studies related to animal nutrition, growth and health. In this paper, a system to classify chewing patterns of ruminants in in vivo experiments is developed. The proposal is based on data collected by optical fiber Bragg grating sensors (FBG) that are processed by machine learning techniques. The FBG sensors measure the biomechanical strain during jaw movements, and a decision tree is responsible for the classification of the associated chewing pattern. In this study, patterns associated with food intake of dietary supplement, hay and ryegrass were considered. Additionally, two other important events for ingestive behavior were monitored: rumination and idleness. Experimental results show that the proposed approach for pattern classification is capable of differentiating the five patterns involved in the chewing process with an overall accuracy of 94%.

In Vivo Pattern Classification of Ingestive Behavior in Ruminants Using FBG Sensors and Machine Learning

PubMed Central

Pegorini, Vinicius; Karam, Leandro Zen; Pitta, Christiano Santos Rocha; Cardoso, Rafael; da Silva, Jean Carlos Cardozo; Kalinowski, Hypolito José; Ribeiro, Richardson; Bertotti, Fábio Luiz; Assmann, Tangriani Simioni

2015-01-01

Pattern classification of ingestive behavior in grazing animals has extreme importance in studies related to animal nutrition, growth and health. In this paper, a system to classify chewing patterns of ruminants in in vivo experiments is developed. The proposal is based on data collected by optical fiber Bragg grating sensors (FBG) that are processed by machine learning techniques. The FBG sensors measure the biomechanical strain during jaw movements, and a decision tree is responsible for the classification of the associated chewing pattern. In this study, patterns associated with food intake of dietary supplement, hay and ryegrass were considered. Additionally, two other important events for ingestive behavior were monitored: rumination and idleness. Experimental results show that the proposed approach for pattern classification is capable of differentiating the five patterns involved in the chewing process with an overall accuracy of 94%. PMID:26569250

Self-regulation via neural simulation

PubMed Central

Gilead, Michael; Boccagno, Chelsea; Silverman, Melanie; Hassin, Ran R.; Weber, Jochen; Ochsner, Kevin N.

2016-01-01

Can taking the perspective of other people modify our own affective responses to stimuli? To address this question, we examined the neurobiological mechanisms supporting the ability to take another person’s perspective and thereby emotionally experience the world as they would. We measured participants’ neural activity as they attempted to predict the emotional responses of two individuals that differed in terms of their proneness to experience negative affect. Results showed that behavioral and neural signatures of negative affect (amygdala activity and a distributed multivoxel pattern reflecting affective negativity) simulated the presumed affective state of the target person. Furthermore, the anterior medial prefrontal cortex (mPFC)—a region implicated in mental state inference—exhibited a perspective-dependent pattern of connectivity with the amygdala, and the multivoxel pattern of activity within the mPFC differentiated between the two targets. We discuss the implications of these findings for research on perspective-taking and self-regulation. PMID:27551094

Differential proteomics analysis of Frankliniella occidentalis immune response after infection with Tomato spotted wilt virus (Tospovirus).

PubMed

Ogada, Pamella Akoth; Kiirika, Leonard Muriithi; Lorenz, Christin; Senkler, Jennifer; Braun, Hans-Peter; Poehling, Hans-Michael

2017-02-01

Tomato spotted wilt virus (TSWV) is mainly vectored by Frankliniella occidentalis Pergande, and it potentially activates the vector's immune response. However, molecular background of the altered immune response is not clearly understood. Therefore, using a proteomic approach, we investigated the immune pathways that are activated in F. occidentalis larvae after 24 h exposure to TSWV. Two-dimensional isoelectric focusing/sodium dodecyl sulfate polyacrylamide gel electrophoresis (2D-IEF/SDS/PAGE) combined with mass spectrometry (MS), were used to identify proteins that were differentially expressed upon viral infection. High numbers of proteins were abundantly expressed in F. occidentalis exposed to TSWV (73%) compared to the non-exposed (27%), with the majority functionally linked to the innate immune system such as: signaling, stress response, defense response, translation, cellular lipids and nucleotide metabolism. Key proteins included: 70 kDa heat shock proteins, Ubiquitin and Dermcidin, among others, indicative of a responsive pattern of the vector's innate immune system to viral infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

The founder-cell transcriptome in the Arabidopsis apetala1 cauliflower inflorescence meristem.

PubMed

Frerichs, Anneke; Thoma, Rahere; Abdallah, Ali Taleb; Frommolt, Peter; Werr, Wolfgang; Chandler, John William

2016-11-03

Although the pattern of lateral organ formation from apical meristems establishes species-specific plant architecture, the positional information that confers cell fate to cells as they transit to the meristem flanks where they differentiate, remains largely unknown. We have combined fluorescence-activated cell sorting and RNA-seq to characterise the cell-type-specific transcriptome at the earliest developmental time-point of lateral organ formation using DORNRÖSCHEN-LIKE::GFP to mark founder-cell populations at the periphery of the inflorescence meristem (IM) in apetala1 cauliflower double mutants, which overproliferate IMs. Within the lateral organ founder-cell population at the inflorescence meristem, floral primordium identity genes are upregulated and stem-cell identity markers are downregulated. Additional differentially expressed transcripts are involved in polarity generation and boundary formation, and in epigenetic and post-translational changes. However, only subtle transcriptional reprogramming within the global auxin network was observed. The transcriptional network of differentially expressed genes supports the hypothesis that lateral organ founder-cell specification involves the creation of polarity from the centre to the periphery of the IM and the establishment of a boundary from surrounding cells, consistent with bract initiation. However, contrary to the established paradigm that sites of auxin response maxima pre-pattern lateral organ initiation in the IM, auxin response might play a minor role in the earliest stages of lateral floral initiation.

Stress Sensitivity Is Associated with Differential Accumulation of Reactive Oxygen and Nitrogen Species in Maize Genotypes with Contrasting Levels of Drought Tolerance

PubMed Central

Yang, Liming; Fountain, Jake C.; Wang, Hui; Ni, Xinzhi; Ji, Pingsheng; Lee, Robert D.; Kemerait, Robert C.; Scully, Brian T.; Guo, Baozhu

2015-01-01

Drought stress decreases crop growth, yield, and can further exacerbate pre-harvest aflatoxin contamination. Tolerance and adaptation to drought stress is an important trait of agricultural crops like maize. However, maize genotypes with contrasting drought tolerances have been shown to possess both common and genotype-specific adaptations to cope with drought stress. In this research, the physiological and metabolic response patterns in the leaves of maize seedlings subjected to drought stress were investigated using six maize genotypes including: A638, B73, Grace-E5, Lo964, Lo1016, and Va35. During drought treatments, drought-sensitive maize seedlings displayed more severe symptoms such as chlorosis and wilting, exhibited significant decreases in photosynthetic parameters, and accumulated significantly more reactive oxygen species (ROS) and reactive nitrogen species (RNS) than tolerant genotypes. Sensitive genotypes also showed rapid increases in enzyme activities involved in ROS and RNS metabolism. However, the measured antioxidant enzyme activities were higher in the tolerant genotypes than in the sensitive genotypes in which increased rapidly following drought stress. The results suggest that drought stress causes differential responses to oxidative and nitrosative stress in maize genotypes with tolerant genotypes with slower reaction and less ROS and RNS production than sensitive ones. These differential patterns may be utilized as potential biological markers for use in marker assisted breeding. PMID:26492235

Machine Learning–Based Differential Network Analysis: A Study of Stress-Responsive Transcriptomes in Arabidopsis[W

PubMed Central

Ma, Chuang; Xin, Mingming; Feldmann, Kenneth A.; Wang, Xiangfeng

2014-01-01

Machine learning (ML) is an intelligent data mining technique that builds a prediction model based on the learning of prior knowledge to recognize patterns in large-scale data sets. We present an ML-based methodology for transcriptome analysis via comparison of gene coexpression networks, implemented as an R package called machine learning–based differential network analysis (mlDNA) and apply this method to reanalyze a set of abiotic stress expression data in Arabidopsis thaliana. The mlDNA first used a ML-based filtering process to remove nonexpressed, constitutively expressed, or non-stress-responsive “noninformative” genes prior to network construction, through learning the patterns of 32 expression characteristics of known stress-related genes. The retained “informative” genes were subsequently analyzed by ML-based network comparison to predict candidate stress-related genes showing expression and network differences between control and stress networks, based on 33 network topological characteristics. Comparative evaluation of the network-centric and gene-centric analytic methods showed that mlDNA substantially outperformed traditional statistical testing–based differential expression analysis at identifying stress-related genes, with markedly improved prediction accuracy. To experimentally validate the mlDNA predictions, we selected 89 candidates out of the 1784 predicted salt stress–related genes with available SALK T-DNA mutagenesis lines for phenotypic screening and identified two previously unreported genes, mutants of which showed salt-sensitive phenotypes. PMID:24520154

Morphogen and community effects determine cell fates in response to BMP4 signaling in human embryonic stem cells.

PubMed

Nemashkalo, Anastasiia; Ruzo, Albert; Heemskerk, Idse; Warmflash, Aryeh

2017-09-01

Paracrine signals maintain developmental states and create cell fate patterns in vivo and influence differentiation outcomes in human embryonic stem cells (hESCs) in vitro Systematic investigation of morphogen signaling is hampered by the difficulty of disentangling endogenous signaling from experimentally applied ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells ('µColonies') to quantitatively investigate paracrine signaling and the response to external stimuli. We examine BMP4-mediated differentiation in µColonies and standard culture conditions and find that in µColonies, above a threshold concentration, BMP4 gives rise to only a single cell fate, contrary to its role as a morphogen in other developmental systems. Under standard culture conditions BMP4 acts as a morphogen but this requires secondary signals and particular cell densities. We find that a 'community effect' enforces a common fate within µColonies, both in the state of pluripotency and when cells are differentiated, and that this effect allows a more precise response to external signals. Using live cell imaging to correlate signaling histories with cell fates, we demonstrate that interactions between neighbors result in sustained, homogenous signaling necessary for differentiation. © 2017. Published by The Company of Biologists Ltd.

Response-food delay gradients for lever pressing and schedule-induced licking in rats.

PubMed

Pellón, Ricardo; Pérez-Padilla, Angeles

2013-06-01

Eight food-deprived Wistar rats developed stable patterns of lever pressing and licking when exposed to a fixed-time 30-s schedule of food pellet presentation. The rats were trained to lever press by presenting the lever 10 s before the programmed food delivery, with the food pellet being delivered immediately upon a lever press. The operant contingency was then removed and the lever was inserted through the entire interfood interval, being withdrawn with food delivery and reinserted 2 s later. On successive phases of the study, a protective contingency postponed food delivery if responses (lever presses or licks) occurred within the last 1, 2, 5, 10, 20, or 25 s of the interfood interval. Lever pressing was reduced at much shorter response-food delays than those that reduced licking. These results demonstrate that reinforcement contributes to the maintenance of different response patterns on periodic schedules, and that different responses are differentially sensitive to delays.

Multiple functions of GABA A and GABA B receptors during pattern processing in the zebrafish olfactory bulb.

PubMed

Tabor, Rico; Yaksi, Emre; Friedrich, Rainer W

2008-07-01

gamma-Aminobutyric acid (GABA)ergic synapses are thought to play pivotal roles in the processing of activity patterns in the olfactory bulb (OB), but their functions have been difficult to study during odor responses in the intact system. We pharmacologically manipulated GABA(A) and GABA(B) receptors in the OB of zebrafish and analysed the effects on odor responses of the output neurons, the mitral cells (MCs), by electrophysiological recordings and temporally deconvolved two-photon Ca2+ imaging. The blockade of GABA(B) receptors enhanced presynaptic Ca2+ influx into afferent axon terminals, and changed the amplitude and time course of a subset of MC responses, indicating that GABA(B) receptors have a modulatory influence on OB output activity. The blockade of GABA(A) receptors induced epileptiform firing, enhanced excitatory responses and abolished fast oscillations in the local field potential. Moreover, the topological reorganization and decorrelation of MC activity patterns during the initial phase of the response was perturbed. These results indicate that GABA(A) receptor-containing circuits participate in the balance of excitation and inhibition, the regulation of total OB output activity, the synchronization of odor-dependent neuronal ensembles, and the reorganization of odor-encoding activity patterns. GABA(A) and GABA(B) receptors are therefore differentially involved in multiple functions of neuronal circuits in the OB.

Mother-infant interaction during the first 3 months: the emergence of culture-specific contingency patterns.

PubMed

Kärtner, Joscha; Keller, Heidi; Yovsi, Relindis D

2010-01-01

This study analyzed German and Nso mothers' auditory, proximal, and visual contingent responses to their infants' nondistress vocalizations in postnatal Weeks 4, 6, 8, 10, and 12. Visual contingency scores increased whereas proximal contingency scores decreased over time for the independent (German urban middle-class, N = 20) but not the interdependent sociocultural context (rural Nso farmers, N = 24). It seems, therefore, that culture-specific differences in the modal patterns of contingent responsiveness emerge during the 2nd and 3rd months of life. This differential development was interpreted as the result of the interplay between maturational processes associated with the 2-month shift that are selectively integrated and reinforced in culture-specific mother-infant interaction.

Changes in EEG alpha power to different disgust elicitors: the specificity of mutilations.

PubMed

Sarlo, Michela; Buodo, Giulia; Poli, Silvia; Palomba, Daniela

2005-07-15

It is unclear in the literature whether the various disgust elicitors are differentially processed by the brain and/or able to elicit distinct psychophysiological response patterns. On the other hand, disgusting stimuli depicting mutilations have been proved to elicit a distinct autonomic response pattern and to demand greater attentional resources, as compared with other unpleasant visual stimuli. In this EEG study, 34 participants viewed 4 film-clips depicting surgery, cockroach invasion, human attack and neutral landscape during EEG recording, and then rated the clips for valence, arousal and the basic emotions. Independent of location, the highest cortical activation was found during the viewing of the surgery scene. Moreover, the above activation was prominent over the right posterior regions.

Patterns and profiles of response to incivility in the workplace.

PubMed

Cortina, Lilia M; Magley, Vicki J

2009-07-01

The authors draw on stress and coping theory to understand patterns of individual response to workplace incivility. According to data from 3 employee samples, incivility tended to trigger mildly negative appraisals, which could theoretically differentiate incivility from other categories of antisocial work behavior. Employees experiencing frequent and varied incivility from powerful instigators generally appraised their uncivil encounters more negatively. They responded to this stressor using a multifaceted array of coping strategies, which entailed support seeking, detachment, minimization, prosocial conflict avoidance, and assertive conflict avoidance. These coping reactions depended on the target's appraisal of the situation, the situation's duration, and the organizational position and power of both target and instigator. Implications for organizational science and practice are discussed. (c) 2009 APA, all rights reserved.

Automatic differentiation of melanoma and clark nevus skin lesions

NASA Astrophysics Data System (ADS)

LeAnder, R. W.; Kasture, A.; Pandey, A.; Umbaugh, S. E.

2007-03-01

Skin cancer is the most common form of cancer in the United States. Although melanoma accounts for just 11% of all types of skin cancer, it is responsible for most of the deaths, claiming more than 7910 lives annually. Melanoma is visually difficult for clinicians to differentiate from Clark nevus lesions which are benign. The application of pattern recognition techniques to these lesions may be useful as an educational tool for teaching physicians to differentiate lesions, as well as for contributing information about the essential optical characteristics that identify them. Purpose: This study sought to find the most effective features to extract from melanoma, melanoma in situ and Clark nevus lesions, and to find the most effective pattern-classification criteria and algorithms for differentiating those lesions, using the Computer Vision and Image Processing Tools (CVIPtools) software package. Methods: Due to changes in ambient lighting during the photographic process, color differences between images can occur. These differences were minimized by capturing dermoscopic images instead of photographic images. Differences in skin color between patients were minimized via image color normalization, by converting original color images to relative-color images. Relative-color images also helped minimize changes in color that occur due to changes in the photographic and digitization processes. Tumors in the relative-color images were segmented and morphologically filtered. Filtered, relative-color, tumor features were then extracted and various pattern-classification schemes were applied. Results: Experimentation resulted in four useful pattern classification methods, the best of which was an overall classification rate of 100% for melanoma and melanoma in situ (grouped) and 60% for Clark nevus. Conclusion: Melanoma and melanoma in situ have feature parameters and feature values that are similar enough to be considered one class of tumor that significantly differs from Clark nevus. Consequently, grouping melanoma and melanoma in situ together achieves the best results in classifying and automatically differentiating melanoma from Clark nevus lesions.

Cancer Modeling: From Optimal Cell Renewal to Immunotherapy

NASA Astrophysics Data System (ADS)

Alvarado Alvarado, Cesar Leonardo

Cancer is a disease caused by mutations in normal cells. According to the National Cancer Institute, in 2016, an estimated 1.6 million people were diagnosed and approximately 0.5 million people died from the disease in the United States. There are many factors that shape cancer at the cellular and organismal level, including genetic, immunological, and environmental components. In this thesis, we show how mathematical modeling can be used to provide insight into some of the key mechanisms underlying cancer dynamics. First, we use mathematical modeling to investigate optimal homeostatic cell renewal in tissues such as the small intestine with an emphasis on division patterns and tissue architecture. We find that the division patterns that delay the accumulation of mutations are strictly associated with the population sizes of the tissue. In particular, patterns with long chains of differentiation delay the time to observe a second-hit mutant, which is important given that for many cancers two mutations are enough to initiate a tumor. We also investigated homeostatic cell renewal under a selective pressure and find that hierarchically organized tissues act as suppressors of selection; we find that an architecture with a small number of stem cells and larger pools of transit amplifying cells and mature differentiated cells, together with long chains of differentiation, form a robust evolutionary strategy to delay the time to observe a second-hit mutant when mutations acquire a fitness advantage or disadvantage. We also formulate a model of the immune response to cancer in the presence of costimulatory and inhibitory signals. We demonstrate that the coordination of such signals is crucial to initiate an effective immune response, and while immunotherapy has become a promising cancer treatment over the past decade, these results offer some explanations for why it can fail.

Interindividual Differences in Neonatal Imitation and the Development of Action Chains in Rhesus Macaques

ERIC Educational Resources Information Center

Ferrari, Pier Francesco; Paukner, Annika; Ruggiero, Angela; Darcey, Lisa; Unbehagen, Sarah; Suomi, Stephen J.

2009-01-01

The capacity to imitate facial gestures is highly variable in rhesus macaques and this variability may be related to differences in specific neurobehavioral patterns of development. This study evaluated the differential neonatal imitative response of 41 macaques in relation to the development of sensory, motor, and cognitive skills throughout the…

The Actifier: A Device for Neurophysiological Studies of Orofacial Control in Human Infants.

ERIC Educational Resources Information Center

Finan, Donald S.; Barlow, Steven M.

1996-01-01

This study examined responsiveness of the suck central pattern generator to external stimulation, based on premise that early control of sucking and smiling sets stage for more differentiated use of orofacial muscle system for speech. A device for the stimulation of intraoral tissues in neonates, called the actifier, features a wide frequency…

Who Defends the Stem Cell's Citadel?

PubMed

Strick-Marchand, Hélène; Durantel, David

2018-03-01

Recently in Cell, Wu et al. (2018) demonstrated that intrinsic expression of a subset of interferon stimulated genes confers resistance to viral infections in stem cells both in vitro and in vivo, while differentiated cells lose this intrinsic gatekeeper expression pattern in favor of inducible interferon responses. Copyright © 2018 Elsevier Inc. All rights reserved.

Children's Time Use: Labor Divisions and Schooling in Indonesia

ERIC Educational Resources Information Center

Hsin, Amy

2007-01-01

Data from the Worker and Iron Status Evaluation are used to examine gendered patterns in children's time in market and nonmarket work, schooling, and leisure in Indonesia (N = 2,929). Boys spend more time in market work; girls spend more time in nonmarket work. Work responsibilities increase with age as well as gender differentials in children's…

Translational head movements of pigeons in response to a rotating pattern: characteristics and tool to analyse mechanisms underlying detection of rotational and translational optical flow.

PubMed

Nalbach, H O

1992-01-01

Pigeons freely standing in the centre of a two-dimensionally textured cylinder not only rotate but also laterally translate their head in response to the pattern sinusoidally oscillating or unidirectionally rotating around their vertical axis. The translational head movement dominates the response at high oscillation frequencies, whereas in a unidirectionally rotating drum head translation declines at about the same rate as the rotational response increases. It is suggested that this is a consequence of charging the 'velocity storage' in the vestibulo-ocular system. Similar to the rotational head movement (opto-collic reflex), the translational head movement is elicited via a wide-field motion sensitive system. The underlying mechanism can be described as vector integration of movement vectors tangential to the pattern rotation. Stimulation of the frontal visual field elicits largest translational responses while rotational responses can be elicited equally well from any azimuthal position of a moving pattern. Experiments where most of the pattern is occluded by a screen and the pigeon is allowed to view the stimulus through one or two windows demonstrate a short-range inhibition and long-range excitation between movement detectors that feed into the rotational system. Furthermore, the results obtained from such types of experiments suggest that the rotational system inhibits the translational system. These mechanisms may help the pigeon to decompose image flow into its translational and rotational components. Because of their translational response to a rotational stimulus, it is concluded, however, that pigeons either generally cannot perfectly perform the task or they need further visual information, like differential image motion, that was not available to them in the paradigms.

Mother-Infant Socioemotional Contingent Responding in Families by Adoption and Birth

PubMed Central

Suwalsky, Joan T. D.; Cote, Linda R.; Bornstein, Marc H.; Hendricks, Charlene; Haynes, O. Maurice; Bakeman, Roger

2014-01-01

Contingencies of three maternal and two infant socioemotional behaviors that are universal components of mother-infant interaction were investigated at 5 months in 62 mothers (31 who had adopted domestically and 31 who had given birth) and their first children (16 males in each group). Patterns of contingent responding were largely comparable in dyads by adoption and birth, although the two groups of mothers responded differentially to the two types of infant signals. Mothers in both groups were more responsive than infants in social and vocal interactions, but infants were more responsive in maternal speech-infant attention interactions. Family type x Gender statistical interactions suggested a possible differential role of infant gender in establishing mother-infant contingencies in families by adoption and birth. PMID:22721748

Migration and Tissue Tropism of Innate Lymphoid Cells

PubMed Central

Kim, Chang H.; Hashimoto-Hill, Seika; Kim, Myunghoo

2016-01-01

Innate lymphoid cell (ILCs) subsets differentially populate various barrier and non-barrier tissues, where they play important roles in tissue homeostasis and tissue-specific responses to pathogen attack. Recent findings have provided insight into the molecular mechanisms that guide ILC migration into peripheral tissues, revealing common features among different ILC subsets as well as important distinctions. Recent studies have also highlighted the impact of tissue-specific cues on ILC migration, and the importance of the local immunological milieu. We review these findings here and discuss how the migratory patterns and tissue tropism of different ILC subsets relate to the development and differentiation of these cells, and to ILC-mediated tissue-specific regulation of innate and adaptive immune responses. In this context we outline open questions and important areas of future research. PMID:26708278

Identification of differentially expressed proteins in Ostrinia furnacalis adults after exposure to ultraviolet A.

PubMed

Zhang, Changyu; Meng, Jianyu

2018-06-23

Ultraviolet A (UVA), the major component of solar UV irradiation, is an important environmental factor inducing damage to insects including cell death, photoreceptor damage, and oxidative stress. In order to improve understanding of the adaptation mechanisms of insect after UVA exposure, a comparative proteomic analysis was carried out to reveal differential protein expression in Ostrinia furnacalis. Three-day-old adults were treated with UVA for 1 h. Total proteins of control and UVA-treated insects were examined using two-dimensional electrophoresis (2-DE). 2-DE analysis demonstrated that 19 proteins were increased and 18 proteins were decreased significantly in O. furnacalis after UVA exposure, respectively. Thirty differentially expressed proteins were successfully identified by mass spectrometry. The identified proteins were involved in diverse biological processes, such as signal transduction, transport processing, cellular stress, metabolisms, and cytoskeleton organization. Our results reveal that the response patterns of O. furnacalis to UVA irradiation are complex and provide novel insights into the adaptation response to UVA irradiation stress.

Bioinspired M-13 bacteriophage-based photonic nose for differential cell recognition† †Electronic supplementary information (ESI) available: Instrumentation, diagrams, protein sequences and additional results. See DOI: 10.1039/c6sc02021f Click here for additional data file.

PubMed Central

Moon, Jong-Sik; Kim, Won-Geun; Shin, Dong-Myeong; Lee, So-Young; Kim, Chuntae; Lee, Yujin; Han, Jiye; Kim, Kyujung

2017-01-01

A bioinspired M-13 bacteriophage-based photonic nose was developed for differential cell recognition. The M-13 bacteriophage-based photonic nose exhibits characteristic color patterns when phage bundle nanostructures, which were genetically modified to selectively capture vapor phase molecules, are structurally deformed. We characterized the color patterns of the phage bundle nanostructure in response to cell proliferation via several biomarkers differentially produced by cells, including hydrazine, o-xylene, ethylbenzene, ethanol and toluene. A specific color enables the successful identification of different types of molecular and cellular species. Our sensing technique utilized the versatile M-13 bacteriophage as a building block for fabricating bioinspired photonic crystals, which enables ease of fabrication and tunable selectivity through genetic engineering. Our simple and versatile bioinspired photonic nose could have possible applications in sensors for human health and national security, food discrimination, environmental monitoring, and portable and wearable sensors. PMID:28572902

Circadian rhythms regulate amelogenesis.

PubMed

Zheng, Li; Seon, Yoon Ji; Mourão, Marcio A; Schnell, Santiago; Kim, Doohak; Harada, Hidemitsu; Papagerakis, Silvana; Papagerakis, Petros

2013-07-01

Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of the development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24 h) intervals both at RNA and protein levels. This study also reveals that the two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory stage ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation stage ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stages of amelogenesis might be under circadian control. Changes in clock gene expression patterns might result in significant alterations of enamel apposition and mineralization. Copyright © 2013 Elsevier Inc. All rights reserved.

The SULTR gene family in maize (Zea mays L.): Gene cloning and expression analyses under sulfate starvation and abiotic stress.

PubMed

Huang, Qin; Wang, Meiping; Xia, Zongliang

2018-01-01

Sulfur is an essential macronutrient required for plant growth, development and stress responses. The family of sulfate transporters (SULTRs) mediates the uptake and translocation of sulfate in higher plants. However, basic knowledge of the SULTR gene family in maize (Zea mays L.) is scarce. In this study, a genome-wide bioinformatic analysis of SULTR genes in maize was conducted, and the developmental expression patterns of the genes and their responses to sulfate starvation and abiotic stress were further investigated. The ZmSULTR family includes eight putative members in the maize genome and is clustered into four groups in the phylogenetic tree. These genes displayed differential expression patterns in various organs of maize. For example, expression of ZmSULTR1;1 and ZmSULTR4;1 was high in roots, and transcript levels of ZmSULTR3;1 and ZmSULTR3;3 were high in shoots. Expression of ZmSULTR1;2, ZmSULTR2;1, ZmSULTR3;3, and ZmSULTR4;1 was high in flowers. Also, these eight genes showed differential responses to sulfate deprivation in roots and shoots of maize seedlings. Transcript levels of ZmSULTR1;1, ZmSULTR1;2, and ZmSULTR3;4 were significantly increased in roots during 12-day-sulfate starvation stress, while ZmSULTR3;3 and ZmSULTR3;5 only showed an early response pattern in shoots. In addition, dynamic transcriptional changes determined via qPCR revealed differential expression profiles of these eight ZmSULTR genes in response to environmental stresses such as salt, drought, and heat stresses. Notably, all the genes, except for ZmSULTR3;3, were induced by drought and heat stresses. However, a few genes were induced by salt stress. Physiological determination showed that two important thiol-containing compounds, cysteine and glutathione, increased significantly under these abiotic stresses. The results suggest that members of the SULTR family might function in adaptations to sulfur deficiency stress and adverse growing environments. This study will lay a foundation for better understanding the functional diversity of the SULTR family and exploring genes of interest for genetic improvement of sulfur use efficiency in cereal crop plants. Copyright © 2017 Elsevier GmbH. All rights reserved.

Respiratory and metabolic acidosis differentially affect the respiratory neuronal network in the ventral medulla of neonatal rats.

PubMed

Okada, Yasumasa; Masumiya, Haruko; Tamura, Yoshiyasu; Oku, Yoshitaka

2007-11-01

Two respiratory-related areas, the para-facial respiratory group/retrotrapezoid nucleus (pFRG/RTN) and the pre-Bötzinger complex/ventral respiratory group (preBötC/VRG), are thought to play key roles in respiratory rhythm. Because respiratory output patterns in response to respiratory and metabolic acidosis differ, we hypothesized that the responses of the medullary respiratory neuronal network to respiratory and metabolic acidosis are different. To test these hypotheses, we analysed respiratory-related activity in the pFRG/RTN and preBötC/VRG of the neonatal rat brainstem-spinal cord in vitro by optical imaging using a voltage-sensitive dye, and compared the effects of respiratory and metabolic acidosis on these two populations. We found that the spatiotemporal responses of respiratory-related regional activities to respiratory and metabolic acidosis are fundamentally different, although both acidosis similarly augmented respiratory output by increasing respiratory frequency. PreBötC/VRG activity, which is mainly inspiratory, was augmented by respiratory acidosis. Respiratory-modulated pixels increased in the preBötC/VRG area in response to respiratory acidosis. Metabolic acidosis shifted the respiratory phase in the pFRG/RTN; the pre-inspiratory dominant pattern shifted to inspiratory dominant. The responses of the pFRG/RTN activity to respiratory and metabolic acidosis are complex, and involve either augmentation or reduction in the size of respiratory-related areas. Furthermore, the activation pattern in the pFRG/RTN switched bi-directionally between pre-inspiratory/inspiratory and post-inspiratory. Electrophysiological study supported the results of our optical imaging study. We conclude that respiratory and metabolic acidosis differentially affect activities of the pFRG/RTN and preBötC/VRG, inducing switching and shifts of the respiratory phase. We suggest that they differently influence the coupling states between the pFRG/RTN and preBötC/VRG.

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

NASA Astrophysics Data System (ADS)

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

2004-10-01

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

Marmoset induced pluripotent stem cells: Robust neural differentiation following pretreatment with dimethyl sulfoxide.

PubMed

Qiu, Zhifang; Mishra, Anuja; Li, Miao; Farnsworth, Steven L; Guerra, Bernadette; Lanford, Robert E; Hornsby, Peter J

2015-07-01

The marmoset is an important nonhuman primate model for regenerative medicine. For experimental autologous cell therapy based on induced pluripotent (iPS) cells in the marmoset, cells must be able to undergo robust and reliable directed differentiation that will not require customization for each specific iPS cell clone. When marmoset iPS cells were aggregated in a hanging drop format for 3 days, followed by exposure to dual SMAD inhibitors and retinoic acid in monolayer culture for 3 days, we found substantial variability in the response of different iPS cell clones. However, when clones were pretreated with 0.05-2% dimethyl sulfoxide (DMSO) for 24 hours, all clones showed a very similar maximal response to the directed differentiation scheme. Peak responses were observed at 0.5% DMSO in two clones and at 1% DMSO in a third clone. When patterns of gene expression were examined by microarray analysis, hierarchical clustering showed very similar responses in all 3 clones when they were pretreated with optimal DMSO concentrations. The change in phenotype following exposure to DMSO and the 6 day hanging drop/monolayer treatment was confirmed by immunocytochemistry. Analysis of DNA content in DMSO-exposed cells indicated that it is unlikely that DMSO acts by causing cells to exit from the cell cycle. This approach should be generally valuable in the directed neural differentiation of pluripotent cells for experimental cell therapy. Copyright © 2015. Published by Elsevier B.V.

Neonatal Persistent Exposure to 6-Propyl-2-thiouracil, a Thyroid-Disrupting Chemical, Differentially Modulates Expression of Hepatic Catalase and C/EBP-β in Adult Rats.

PubMed

Bunker, Suresh Kumar; Dandapat, Jagneshwar; Sahoo, Sunil Kumar; Roy, Anita; Chainy, Gagan B N

2016-02-01

Persistent exposure of rats to 6-propyl-2-thiouracil (PTU) from birth resulted in decreases in plasma thyroid hormone (TH) levels and hepatic expression of catalase and CCAAT enhancer binding protein β (C/EBP-β). Catalase promoter region (-185 to +52) that contains binding sites for C/EBP-β showed an augmentation in the methylation level along with a change in methylation pattern of CpG islands in response to PTU treatment. PTU withdrawal on 30 days of birth restored TH levels and C/EBP-β to control rats in adulthood. Although catalase expression was restored to some extent in adult rats in response to PTU withdrawal, a permanent change in its promoter CpG methylation pattern was recorded. The results suggest that downregulation of adult hepatic catalase gene in response to persistent neonatal PTU exposure may not solely be attributed to thyroid-disrupting properties of PTU. It is possible that besides thyroid-disrupting behavior, PTU may impair expression of hepatic catalase by altering methylation pattern of its promoter. © 2015 Wiley Periodicals, Inc.

Auditory stream segregation in monkey auditory cortex: effects of frequency separation, presentation rate, and tone duration

NASA Astrophysics Data System (ADS)

Fishman, Yonatan I.; Arezzo, Joseph C.; Steinschneider, Mitchell

2004-09-01

Auditory stream segregation refers to the organization of sequential sounds into ``perceptual streams'' reflecting individual environmental sound sources. In the present study, sequences of alternating high and low tones, ``...ABAB...,'' similar to those used in psychoacoustic experiments on stream segregation, were presented to awake monkeys while neural activity was recorded in primary auditory cortex (A1). Tone frequency separation (ΔF), tone presentation rate (PR), and tone duration (TD) were systematically varied to examine whether neural responses correlate with effects of these variables on perceptual stream segregation. ``A'' tones were fixed at the best frequency of the recording site, while ``B'' tones were displaced in frequency from ``A'' tones by an amount=ΔF. As PR increased, ``B'' tone responses decreased in amplitude to a greater extent than ``A'' tone responses, yielding neural response patterns dominated by ``A'' tone responses occurring at half the alternation rate. Increasing TD facilitated the differential attenuation of ``B'' tone responses. These findings parallel psychoacoustic data and suggest a physiological model of stream segregation whereby increasing ΔF, PR, or TD enhances spatial differentiation of ``A'' tone and ``B'' tone responses along the tonotopic map in A1.

Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-derived Mesenchymal Stem Cells*

PubMed Central

Meyer, Mark B.; Benkusky, Nancy A.; Sen, Buer; Rubin, Janet; Pike, J. Wesley

2016-01-01

Terminal differentiation of multipotent stem cells is achieved through a coordinated cascade of activated transcription factors and epigenetic modifications that drive gene transcription responsible for unique cell fate. Within the mesenchymal lineage, factors such as RUNX2 and PPARγ are indispensable for osteogenesis and adipogenesis, respectively. We therefore investigated genomic binding of transcription factors and accompanying epigenetic modifications that occur during osteogenic and adipogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (MSCs). As assessed by ChIP-sequencing and RNA-sequencing analyses, we found that genes vital for osteogenic identity were linked to RUNX2, C/EBPβ, retinoid X receptor, and vitamin D receptor binding sites, whereas adipocyte differentiation favored PPARγ, retinoid X receptor, C/EBPα, and C/EBPβ binding sites. Epigenetic marks were clear predictors of active differentiation loci as well as enhancer activities and selective gene expression. These marrow-derived MSCs displayed an epigenetic pattern that suggested a default preference for the osteogenic pathway; however, these patterns were rapidly altered near the Adipoq, Cidec, Fabp4, Lipe, Plin1, Pparg, and Cebpa genes during adipogenic differentiation. Surprisingly, we found that these cells also exhibited an epigenetic plasticity that enabled them to trans-differentiate from adipocytes to osteoblasts (and vice versa) after commitment, as assessed by staining, gene expression, and ChIP-quantitative PCR analysis. The osteogenic default pathway may be subverted during pathological conditions, leading to skeletal fragility and increased marrow adiposity during aging, estrogen deficiency, and skeletal unloading. Taken together, our data provide an increased mechanistic understanding of the epigenetic programs necessary for multipotent differentiation of MSCs that may prove beneficial in the development of therapeutic strategies. PMID:27402842

Establishment of a translational endothelial cell model using directed differentiation of induced pluripotent stem cells from Cynomolgus monkey.

PubMed

Thoma, Eva C; Heckel, Tobias; Keller, David; Giroud, Nicolas; Leonard, Brian; Christensen, Klaus; Roth, Adrian; Bertinetti-Lapatki, Cristina; Graf, Martin; Patsch, Christoph

2016-10-25

Due to their broad differentiation potential, pluripotent stem cells (PSCs) offer a promising approach for generating relevant cellular models for various applications. While human PSC-based cellular models are already advanced, similar systems for non-human primates (NHPs) are still lacking. However, as NHPs are the most appropriate animals for evaluating the safety of many novel pharmaceuticals, the availability of in vitro systems would be extremely useful to bridge the gap between cellular and animal models. Here, we present a NHP in vitro endothelial cell system using induced pluripotent stem cells (IPSCs) from Cynomolgus monkey (Macaca fascicularis). Based on an adapted protocol for human IPSCs, we directly differentiated macaque IPSCs into endothelial cells under chemically defined conditions. The resulting endothelial cells can be enriched using immuno-magnetic cell sorting and display endothelial marker expression and function. RNA sequencing revealed that the differentiation process closely resembled vasculogenesis. Moreover, we showed that endothelial cells derived from macaque and human IPSCs are highly similar with respect to gene expression patterns and key endothelial functions, such as inflammatory responses. These data demonstrate the power of IPSC differentiation technology to generate defined cell types for use as translational in vitro models to compare cell type-specific responses across species.

Empathy, ToM, and self-other differentiation: an fMRI study of internal states.

PubMed

Reniers, Renate L E P; Völlm, Birgit A; Elliott, Rebecca; Corcoran, Rhiannon

2014-02-01

This study used functional magnetic resonance imaging to examine the neural substrates of empathy, Theory of Mind (ToM), and self-other differentiation involved in the adaptive understanding of people's internal states. Three conditions were distinguished in both sad and neutral (no obvious emotion) contexts. The empathy condition involved imagining what another person is feeling while the more cognitively loaded ToM condition involved imagining what would make another person feel better. The self-reference condition required participants to imagine how they would feel in someone else's situation. Areas previously implicated in empathy, ToM, and self-other differentiation were identified within the different conditions, regardless of emotional context. Specifically, the frontal and temporal poles responded more strongly for ToM than for empathy. The self-reference condition was associated with stronger dorsolateral prefrontal response than the empathy condition, while the reverse comparison revealed a stronger role for right frontal pole. Activations in frontal pole and orbitofrontal cortex were shared between the three conditions. Contrasts of parameter estimates demonstrated modulation by emotional context. The findings of common and differential patterns of responding observed in prefrontal and temporal regions suggest that within the social cognition network empathy, ToM and self-other differentiation have distinct roles that are responsive to context.

Gravity-regulated gene expression in Arabidopsis thaliana

NASA Astrophysics Data System (ADS)

Sederoff, Heike; Brown, Christopher S.; Heber, Steffen; Kajla, Jyoti D.; Kumar, Sandeep; Lomax, Terri L.; Wheeler, Benjamin; Yalamanchili, Roopa

Plant growth and development is regulated by changes in environmental signals. Plants sense environmental changes and respond to them by modifying gene expression programs to ad-just cell growth, differentiation, and metabolism. Functional expression of genes comprises many different processes including transcription, translation, post-transcriptional and post-translational modifications, as well as the degradation of RNA and proteins. Recently, it was discovered that small RNAs (sRNA, 18-24 nucleotides long), which are heritable and systemic, are key elements in regulating gene expression in response to biotic and abiotic changes. Sev-eral different classes of sRNAs have been identified that are part of a non-cell autonomous and phloem-mobile network of regulators affecting transcript stability, translational kinetics, and DNA methylation patterns responsible for heritable transcriptional silencing (epigenetics). Our research has focused on gene expression changes in response to gravistimulation of Arabidopsis roots. Using high-throughput technologies including microarrays and 454 sequencing, we iden-tified rapid changes in transcript abundance of genes as well as differential expression of small RNA in Arabidopsis root apices after minutes of reorientation. Some of the differentially regu-lated transcripts are encoded by genes that are important for the bending response. Functional mutants of those genes respond faster to reorientation than the respective wild type plants, indicating that these proteins are repressors of differential cell elongation. We compared the gravity responsive sRNAs to the changes in transcript abundances of their putative targets and identified several potential miRNA: target pairs. Currently, we are using mutant and transgenic Arabidopsis plants to characterize the function of those miRNAs and their putative targets in gravitropic and phototropic responses in Arabidopsis.

Specifying and Sustaining Pigmentation Patterns in Domestic and Wild Cats

PubMed Central

Kaelin, Christopher B.; Xu, Xiao; Hong, Lewis Z.; David, Victor A.; McGowan, Kelly A.; Schmidt-Küntzel, Anne; Roelke, Melody E.; Pino, Javier; Pontius, Joan; Cooper, Gregory M.; Manuel, Hermogenes; Swanson, William F.; Marker, Laurie; Harper, Cindy K.; van Dyk, Ann; Yue, Bisong; Mullikin, James C.; Warren, Wesley C.; Eizirik, Eduardo; Kos, Lidia; O’Brien, Stephen J.; Barsh, Gregory S.; Menotti-Raymond, Marilyn

2013-01-01

Color markings among felid species display both a remarkable diversity and a common underlying periodicity. A similar range of patterns in domestic cats suggests a conserved mechanism whose appearance can be altered by selection. We identified the gene responsible for tabby pattern variation in domestic cats as Transmembrane aminopeptidase Q (Taqpep), which encodes a membrane-bound metalloprotease. Analyzing 31 other felid species, we identified Taqpep as the cause of the rare king cheetah phenotype, in which spots coalesce into blotches and stripes. Histologic, genomic expression, and transgenic mouse studies indicate that paracrine expression of Endothelin3 (Edn3) coordinates localized color differences. We propose a two-stage model in which Taqpep helps to establish a periodic pre-pattern during skin development that is later implemented by differential expression of Edn3. PMID:22997338

Genome-wide DNA methylation reprogramming in response to inorganic arsenic links inhibition of CTCF binding, DNMT expression and cellular transformation

NASA Astrophysics Data System (ADS)

Rea, Matthew; Eckstein, Meredith; Eleazer, Rebekah; Smith, Caroline; Fondufe-Mittendorf, Yvonne N.

2017-02-01

Chronic low dose inorganic arsenic (iAs) exposure leads to changes in gene expression and epithelial-to-mesenchymal transformation. During this transformation, cells adopt a fibroblast-like phenotype accompanied by profound gene expression changes. While many mechanisms have been implicated in this transformation, studies that focus on the role of epigenetic alterations in this process are just emerging. DNA methylation controls gene expression in physiologic and pathologic states. Several studies show alterations in DNA methylation patterns in iAs-mediated pathogenesis, but these studies focused on single genes. We present a comprehensive genome-wide DNA methylation analysis using methyl-sequencing to measure changes between normal and iAs-transformed cells. Additionally, these differential methylation changes correlated positively with changes in gene expression and alternative splicing. Interestingly, most of these differentially methylated genes function in cell adhesion and communication pathways. To gain insight into how genomic DNA methylation patterns are regulated during iAs-mediated carcinogenesis, we show that iAs probably targets CTCF binding at the promoter of DNA methyltransferases, regulating their expression. These findings reveal how CTCF binding regulates DNA methyltransferase to reprogram the methylome in response to an environmental toxin.

Genome-wide DNA methylation reprogramming in response to inorganic arsenic links inhibition of CTCF binding, DNMT expression and cellular transformation

PubMed Central

Rea, Matthew; Eckstein, Meredith; Eleazer, Rebekah; Smith, Caroline; Fondufe-Mittendorf , Yvonne N.

2017-01-01

Chronic low dose inorganic arsenic (iAs) exposure leads to changes in gene expression and epithelial-to-mesenchymal transformation. During this transformation, cells adopt a fibroblast-like phenotype accompanied by profound gene expression changes. While many mechanisms have been implicated in this transformation, studies that focus on the role of epigenetic alterations in this process are just emerging. DNA methylation controls gene expression in physiologic and pathologic states. Several studies show alterations in DNA methylation patterns in iAs-mediated pathogenesis, but these studies focused on single genes. We present a comprehensive genome-wide DNA methylation analysis using methyl-sequencing to measure changes between normal and iAs-transformed cells. Additionally, these differential methylation changes correlated positively with changes in gene expression and alternative splicing. Interestingly, most of these differentially methylated genes function in cell adhesion and communication pathways. To gain insight into how genomic DNA methylation patterns are regulated during iAs-mediated carcinogenesis, we show that iAs probably targets CTCF binding at the promoter of DNA methyltransferases, regulating their expression. These findings reveal how CTCF binding regulates DNA methyltransferase to reprogram the methylome in response to an environmental toxin. PMID:28150704

Pleiotropic Effects of Immune Responses Explain Variation in the Prevalence of Fibroproliferative Diseases

PubMed Central

Russell, Shirley B.; Smith, Joan C.; Huang, Minjun; Trupin, Joel S.; Williams, Scott M.

2015-01-01

Many diseases are differentially distributed among human populations. Differential selection on genetic variants in ancestral environments that coincidentally predispose to disease can be an underlying cause of these unequal prevalence patterns. Selected genes may be pleiotropic, affecting multiple phenotypes and resulting in more than one disease or trait. Patterns of pleiotropy may be helpful in understanding the underlying causes of an array of conditions in a population. For example, several fibroproliferative diseases are more prevalent and severe in populations of sub-Saharan ancestry. We propose that this disparity is due to selection for an enhanced Th2 response that confers resistance to helminthic infections, and concurrently increases susceptibility to fibrosis due to the profibrotic action of Th2 cytokines. Many studies on selection of Th2-related genes for host resistance to helminths have been reported, but the pleiotropic impact of this selection on the distribution of fibrotic disorders has not been explicitly investigated. We discuss the disproportionate occurrence of fibroproliferative diseases in individuals of African ancestry and provide evidence that adaptation of the immune system has shaped the genetic structure of these human populations in ways that alter the distribution of multiple fibroproliferative diseases. PMID:26540410

Fear and disgust in women: Differentiation of cardiovascular regulation patterns.

PubMed

Comtesse, Hannah; Stemmler, Gerhard

2017-02-01

Both fear and disgust facilitate avoidance of threat. From a functional view, however, cardiovascular responses to fear and disgust should differ as they prepare for appropriate behavior to protect from injury and infection, respectively. Therefore, we examined the cardiovascular responses to fear and contamination-related disgust in comparison to an emotionally neutral state induced with auditory scripts and film clips in female participants. Ten emotion and motivation self-reports and ninecardiovascular response factors derived from 23 cardiovascular variables served as dependent variables. Self-reports confirmed the specific induction of fear and disgust. In addition, fear and disgust differed in their cardiovascular response patterning. For fear, we observed specific increases in factors indicating vasoconstriction and cardiac pump function. For disgust, we found specific increases in vagal cardiac control and decreases in myocardial contractility. These findings provide support for the cardiovascular specificity of fear and disgust and are discussed in terms of a basic emotions approach. Copyright © 2016. Published by Elsevier B.V.

Differentiation-associated microRNAs antagonize the Rb–E2F pathway to restrict proliferation

PubMed Central

Marzi, Matteo J.; Puggioni, Eleonora M. R.; Dall'Olio, Valentina; Bucci, Gabriele; Bernard, Loris; Bianchi, Fabrizio; Crescenzi, Marco

2012-01-01

The cancer-associated loss of microRNA (miRNA) expression leads to a proliferative advantage and aggressive behavior through largely unknown mechanisms. Here, we exploit a model system that recapitulates physiological terminal differentiation and its reversal upon oncogene expression to analyze coordinated mRNA/miRNA responses. The cell cycle reentry of myotubes, forced by the E1A oncogene, was associated with a pattern of mRNA/miRNA modulation that was largely reciprocal to that induced during the differentiation of myoblasts into myotubes. The E1A-induced mRNA response was preponderantly Retinoblastoma protein (Rb)-dependent. Conversely, the miRNA response was mostly Rb-independent and exerted through tissue-specific factors and Myc. A subset of these miRNAs (miR-1, miR-34, miR-22, miR-365, miR-29, miR-145, and Let-7) was shown to coordinately target Rb-dependent cell cycle and DNA replication mRNAs. Thus, a dual level of regulation—transcriptional regulation via Rb–E2F and posttranscriptional regulation via miRNAs—confers robustness to cell cycle control and provides a molecular basis to understand the role of miRNA subversion in cancer. PMID:23027903

Familiarity and recollection produce distinct eye movement, pupil and medial temporal lobe responses when memory strength is matched.

PubMed

Kafkas, Alexandros; Montaldi, Daniela

2012-11-01

Two experiments explored eye measures (fixations and pupil response patterns) and brain responses (BOLD) accompanying the recognition of visual object stimuli based on familiarity and recollection. In both experiments, the use of a modified remember/know procedure led to high confidence and matched accuracy levels characterising strong familiarity (F3) and recollection (R) responses. In Experiment 1, visual scanning behaviour at retrieval distinguished familiarity-based from recollection-based recognition. Recollection, relative to strength-matched familiarity, involved significantly larger pupil dilations and more dispersed fixation patterns. In Experiment 2, the hippocampus was selectively activated for recollected stimuli, while no evidence of activation was observed in the hippocampus for strong familiarity of matched accuracy. Recollection also activated the parahippocampal cortex (PHC), while the adjacent perirhinal cortex (PRC) was actively engaged in response to strong familiarity (than to recollection). Activity in prefrontal and parietal areas differentiated familiarity and recollection in both the extent and the magnitude of activity they exhibited, while the dorsomedial thalamus showed selective familiarity-related activity, and the ventrolateral and anterior thalamus selective recollection-related activity. These findings are consistent with the view that the hippocampus and PRC play contrasting roles in supporting recollection and familiarity and that these differences are not a result of differences in memory strength. Overall, the combined pupil dilation, eye movement and fMRI data suggest the operation of recognition mechanisms drawing differentially on familiarity and recollection, whose neural bases are distinct within the MTL. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2008-01-01

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

Differential principal component analysis of ChIP-seq.

PubMed

Ji, Hongkai; Li, Xia; Wang, Qian-fei; Ning, Yang

2013-04-23

We propose differential principal component analysis (dPCA) for analyzing multiple ChIP-sequencing datasets to identify differential protein-DNA interactions between two biological conditions. dPCA integrates unsupervised pattern discovery, dimension reduction, and statistical inference into a single framework. It uses a small number of principal components to summarize concisely the major multiprotein synergistic differential patterns between the two conditions. For each pattern, it detects and prioritizes differential genomic loci by comparing the between-condition differences with the within-condition variation among replicate samples. dPCA provides a unique tool for efficiently analyzing large amounts of ChIP-sequencing data to study dynamic changes of gene regulation across different biological conditions. We demonstrate this approach through analyses of differential chromatin patterns at transcription factor binding sites and promoters as well as allele-specific protein-DNA interactions.

Identification and characterization of novel and differentially expressed microRNAs in peripheral blood from healthy and mastitis Holstein cattle by deep sequencing.

PubMed

Li, Zhixiong; Wang, Hongliang; Chen, Ling; Wang, Lijun; Liu, Xiaolin; Ru, Caixia; Song, Ailong

2014-02-01

MicroRNA (miRNA) mediates post-transcriptional gene regulation and plays an important role in regulating the development of immune cells and in modulating innate and adaptive immune responses in mammals, including cattle. In the present study, we identified novel and differentially expressed miRNAs in peripheral blood from healthy and mastitis Holstein cattle by Solexa sequencing and bioinformatics. In total, 608 precursor hairpins (pre-miRNAs) encoding for 753 mature miRNAs were detected. Statistically, 173 unique miRNAs (of 753, 22.98%) were identified that had significant differential expression between healthy and mastitis Holstein cattle (P < 0.001). Most differentially expressed miRNAs (118 of 173, 68.21%) belonged to the chemokine signaling pathway involved in the immune responses. This study expands the number of miRNAs known to be expressed in cattle. The patterns of miRNAs expression differed significantly between the peripheral blood from healthy and mastitis Holstein cattle, which provide important information on mastitis in miRNAs expression. Diverse miRNAs may play an important role in the treatment of mastitis in Holstein cattle. © 2013 Stichting International Foundation for Animal Genetics.

ϒ Spike-Field Coherence in a Population of Olfactory Bulb Neurons Differentiates between Odors Irrespective of Associated Outcome

PubMed Central

Li, Anan; Gire, David H.

2015-01-01

Studies in different sensory systems indicate that short spike patterns within a spike train that carry items of sensory information can be extracted from the overall train by using field potential oscillations as a reference (Kayser et al., 2012; Panzeri et al., 2014). Here we test the hypothesis that the local field potential (LFP) provides the temporal reference frame needed to differentiate between odors regardless of associated outcome. Experiments were performed in the olfactory system of the mouse (Mus musculus) where the mitral/tufted (M/T) cell spike rate develops differential responses to rewarded and unrewarded odors as the animal learns to associate one of the odors with a reward in a go–no go behavioral task. We found that coherence of spiking in M/T cells with the ϒ LFP (65 to 95 Hz) differentiates between odors regardless of the associated behavioral outcome of odor presentation. PMID:25855190

NEU3 sialidase strictly modulates GM3 levels in skeletal myoblasts C2C12 thus favoring their differentiation and protecting them from apoptosis.

PubMed

Anastasia, Luigi; Papini, Nadia; Colazzo, Francesca; Palazzolo, Giacomo; Tringali, Cristina; Dileo, Loredana; Piccoli, Marco; Conforti, Erika; Sitzia, Clementina; Monti, Eugenio; Sampaolesi, Maurilio; Tettamanti, Guido; Venerando, Bruno

2008-12-26

Membrane-bound sialidase NEU3, often referred to as the "ganglioside sialidase," has a critical regulatory function on the sialoglycosphingolipid pattern of the cell membrane, with an anti-apoptotic function, especially in cancer cells. Although other sialidases have been shown to be involved in skeletal muscle differentiation, the role of NEU3 had yet to be disclosed. Herein we report that NEU3 plays a key role in skeletal muscle differentiation by strictly modulating the ganglioside content of adjacent cells, with special regard to GM3. Induced down-regulation of NEU3 in murine C2C12 myoblasts, even when partial, totally inhibits their capability to differentiate by increasing the GM3 level above a critical point, which causes epidermal growth factor receptor inhibition (and ultimately its down-regulation) and an higher responsiveness of myoblasts to the apoptotic stimuli.

Genetic and epigenetic variation in Spartina alterniflora following the Deepwater Horizon oil spill.

PubMed

Robertson, Marta; Schrey, Aaron; Shayter, Ashley; Moss, Christina J; Richards, Christina

2017-09-01

Catastrophic events offer unique opportunities to study rapid population response to stress in natural settings. In concert with genetic variation, epigenetic mechanisms may allow populations to persist through severe environmental challenges. In 2010, the Deepwater Horizon oil spill devastated large portions of the coastline along the Gulf of Mexico. However, the foundational salt marsh grass, Spartina alterniflora , showed high resilience to this strong environmental disturbance. Following the spill, we simultaneously examined the genetic and epigenetic structure of recovering populations of S. alterniflora to oil exposure. We quantified genetic and DNA methylation variation using amplified fragment length polymorphism and methylation sensitive fragment length polymorphism (MS-AFLP) to test the hypothesis that response to oil exposure in S. alterniflora resulted in genetically and epigenetically based population differentiation. We found high genetic and epigenetic variation within and among sites and found significant genetic differentiation between contaminated and uncontaminated sites, which may reflect nonrandom mortality in response to oil exposure. Additionally, despite a lack of genomewide patterns in DNA methylation between contaminated and uncontaminated sites, we found five MS-AFLP loci (12% of polymorphic MS-AFLP loci) that were correlated with oil exposure. Overall, our findings support genetically based differentiation correlated with exposure to the oil spill in this system, but also suggest a potential role for epigenetic mechanisms in population differentiation.

Hemocyanins Stimulate Innate Immunity by Inducing Different Temporal Patterns of Proinflammatory Cytokine Expression in Macrophages.

PubMed

Zhong, Ta-Ying; Arancibia, Sergio; Born, Raimundo; Tampe, Ricardo; Villar, Javiera; Del Campo, Miguel; Manubens, Augusto; Becker, María Inés

2016-06-01

Hemocyanins induce a potent Th1-dominant immune response with beneficial clinical outcomes when used as a carrier/adjuvant in vaccines and nonspecific immunostimulant in cancer. However, the mechanisms by which hemocyanins trigger innate immune responses, leading to beneficial adaptive immune responses, are unknown. This response is triggered by a proinflammatory signal from various components, of which macrophages are an essential part. To understand how these proteins influence macrophage response, we investigated the effects of mollusks hemocyanins with varying structural and immunological properties, including hemocyanins from Concholepas concholepas, Fissurella latimarginata, and Megathura crenulata (keyhole limpet hemocyanin), on cultures of peritoneal macrophages. Hemocyanins were phagocytosed and slowly processed. Analysis of this process showed differential gene expression along with protein levels of proinflammatory markers, including IL-1β, IL-6, IL-12p40, and TNF-α. An extended expression analysis of 84 cytokines during a 24-h period showed a robust proinflammatory response for F. latimarginata hemocyanin in comparison with keyhole limpet hemocyanin and C. concholepas hemocyanin, which was characterized by an increase in the transcript levels of M1 cytokines involved in leukocyte recruitment. These cytokine genes included chemokines (Cxcl1, Cxcl3, Cxcl5, Ccl2, and Ccl3), ILs (Il1b and Ifng), growth factors (Csf2 and Csf3), and TNF family members (Cd40lg). The protein levels of certain cytokines were increased. However, every hemocyanin maintains downregulated key M2 cytokine genes, including Il4 and Il5 Collectively, our data demonstrate that hemocyanins are able to trigger the release of proinflammatory factors with different patterns of cytokine expression, suggesting differential signaling pathways and transcriptional network mechanisms that lead to the activation of M1-polarized macrophages. Copyright © 2016 by The American Association of Immunologists, Inc.

Hemocyanins Stimulate Innate Immunity by Inducing Different Temporal Patterns of Proinflammatory Cytokine Expression in Macrophages

PubMed Central

Zhong, Ta-Ying; Arancibia, Sergio; Born, Raimundo; Tampe, Ricardo; Villar, Javiera; Del Campo, Miguel; Manubens, Augusto

2016-01-01

Hemocyanins induce a potent Th1-dominant immune response with beneficial clinical outcomes when used as a carrier/adjuvant in vaccines and nonspecific immunostimulant in cancer. However, the mechanisms by which hemocyanins trigger innate immune responses, leading to beneficial adaptive immune responses, are unknown. This response is triggered by a proinflammatory signal from various components, of which macrophages are an essential part. To understand how these proteins influence macrophage response, we investigated the effects of mollusks hemocyanins with varying structural and immunological properties, including hemocyanins from Concholepas concholepas, Fissurella latimarginata, and Megathura crenulata (keyhole limpet hemocyanin), on cultures of peritoneal macrophages. Hemocyanins were phagocytosed and slowly processed. Analysis of this process showed differential gene expression along with protein levels of proinflammatory markers, including IL-1β, IL-6, IL-12p40, and TNF-α. An extended expression analysis of 84 cytokines during a 24-h period showed a robust proinflammatory response for F. latimarginata hemocyanin in comparison with keyhole limpet hemocyanin and C. concholepas hemocyanin, which was characterized by an increase in the transcript levels of M1 cytokines involved in leukocyte recruitment. These cytokine genes included chemokines (Cxcl1, Cxcl3, Cxcl5, Ccl2, and Ccl3), ILs (Il1b and Ifng), growth factors (Csf2 and Csf3), and TNF family members (Cd40lg). The protein levels of certain cytokines were increased. However, every hemocyanin maintains downregulated key M2 cytokine genes, including Il4 and Il5. Collectively, our data demonstrate that hemocyanins are able to trigger the release of proinflammatory factors with different patterns of cytokine expression, suggesting differential signaling pathways and transcriptional network mechanisms that lead to the activation of M1-polarized macrophages. PMID:27183578

Aging of the Immune System. Mechanisms and Therapeutic Targets.

PubMed

Weyand, Cornelia M; Goronzy, Jörg J

2016-12-01

Beginning with the sixth decade of life, the human immune system undergoes dramatic aging-related changes, which continuously progress to a state of immunosenescence. The aging immune system loses the ability to protect against infections and cancer and fails to support appropriate wound healing. Vaccine responses are typically impaired in older individuals. Conversely, inflammatory responses mediated by the innate immune system gain in intensity and duration, rendering older individuals susceptible to tissue-damaging immunity and inflammatory disease. Immune system aging functions as an accelerator for other age-related pathologies. It occurs prematurely in some clinical conditions, most prominently in patients with the autoimmune syndrome rheumatoid arthritis (RA); and such patients serve as an informative model system to study molecular mechanisms of immune aging. T cells from patients with RA are prone to differentiate into proinflammatory effector cells, sustaining chronic-persistent inflammatory lesions in the joints and many other organ systems. RA T cells have several hallmarks of cellular aging; most importantly, they accumulate damaged DNA. Because of deficiency of the DNA repair kinase ataxia telangiectasia mutated, RA T cells carry a higher burden of DNA double-strand breaks, triggering cell-indigenous stress signals that shift the cell's survival potential and differentiation pattern. Immune aging in RA T cells is also associated with metabolic reprogramming; specifically, with reduced glycolytic flux and diminished ATP production. Chronic energy stress affects the longevity and the functional differentiation of older T cells. Altered metabolic patterns provide opportunities to therapeutically target the immune aging process through metabolic interference.

Coral bleaching response index: a new tool to standardize and compare susceptibility to thermal bleaching.

PubMed

Swain, Timothy D; Vega-Perkins, Jesse B; Oestreich, William K; Triebold, Conrad; DuBois, Emily; Henss, Jillian; Baird, Andrew; Siple, Margaret; Backman, Vadim; Marcelino, Luisa

2016-07-01

As coral bleaching events become more frequent and intense, our ability to predict and mitigate future events depends upon our capacity to interpret patterns within previous episodes. Responses to thermal stress vary among coral species; however the diversity of coral assemblages, environmental conditions, assessment protocols, and severity criteria applied in the global effort to document bleaching patterns creates challenges for the development of a systemic metric of taxon-specific response. Here, we describe and validate a novel framework to standardize bleaching response records and estimate their measurement uncertainties. Taxon-specific bleaching and mortality records (2036) of 374 coral taxa (during 1982-2006) at 316 sites were standardized to average percent tissue area affected and a taxon-specific bleaching response index (taxon-BRI) was calculated by averaging taxon-specific response over all sites where a taxon was present. Differential bleaching among corals was widely variable (mean taxon-BRI = 25.06 ± 18.44%, ±SE). Coral response may differ because holobionts are biologically different (intrinsic factors), they were exposed to different environmental conditions (extrinsic factors), or inconsistencies in reporting (measurement uncertainty). We found that both extrinsic and intrinsic factors have comparable influence within a given site and event (60% and 40% of bleaching response variance of all records explained, respectively). However, when responses of individual taxa are averaged across sites to obtain taxon-BRI, differential response was primarily driven by intrinsic differences among taxa (65% of taxon-BRI variance explained), not conditions across sites (6% explained), nor measurement uncertainty (29% explained). Thus, taxon-BRI is a robust metric of intrinsic susceptibility of coral taxa. Taxon-BRI provides a broadly applicable framework for standardization and error estimation for disparate historical records and collection of novel data, allowing for unprecedented accuracy in parameterization of mechanistic and predictive models and conservation plans. © 2016 John Wiley & Sons Ltd.

Coral bleaching response index: a new tool to standardize and compare susceptibility to thermal bleaching

PubMed Central

SWAIN, TIMOTHY D.; VEGA-PERKINS, JESSE B.; OESTREICH, WILLIAM K.; TRIEBOLD, CONRAD; DUBOIS, EMILY; HENSS, JILLIAN; BAIRD, ANDREW; SIPLE, MARGARET; BACKMAN, VADIM; MARCELINO, LUISA

2017-01-01

As coral bleaching events become more frequent and intense, our ability to predict and mitigate future events depends upon our capacity to interpret patterns within previous episodes. Responses to thermal stress vary among coral species; however the diversity of coral assemblages, environmental conditions, assessment protocols, and severity criteria applied in the global effort to document bleaching patterns creates challenges for the development of a systemic metric of taxon-specific response. Here, we describe and validate a novel framework to standardize bleaching response records and estimate their measurement uncertainties. Taxon-specific bleaching and mortality records (2036) of 374 coral taxa (during 1982–2006) at 316 sites were standardized to average percent tissue area affected and a taxon-specific bleaching response index (taxon-BRI) was calculated by averaging taxon-specific response over all sites where a taxon was present. Differential bleaching among corals was widely variable (mean taxon-BRI = 25.06 ± 18.44%, ± SE). Coral response may differ because holobionts are biologically different (intrinsic factors), they were exposed to different environmental conditions (extrinsic factors), or inconsistencies in reporting (measurement uncertainty). We found that both extrinsic and intrinsic factors have comparable influence within a given site and event (60% and 40% of bleaching response variance of all records explained, respectively). However, when responses of individual taxa are averaged across sites to obtain taxon-BRI, differential response was primarily driven by intrinsic differences among taxa (65% of taxon-BRI variance explained), not conditions across sites (6% explained), nor measurement uncertainty (29% explained). Thus, taxon-BRI is a robust metric of intrinsic susceptibility of coral taxa. Taxon-BRI provides a broadly applicable framework for standardization and error estimation for disparate historical records and collection of novel data, allowing for unprecedented accuracy in parameterization of mechanistic and predictive models and conservation plans. PMID:27074334

Dermatoglyphics in childhood leukemia

PubMed Central

Berka, Ludmila; McClure, P. D.; Sonley, Marilyn J.; Thompson, Margaret W.

1971-01-01

The dermatoglyphics of 54 leukemic children do not differ significantly from those of 25 mothers and 592 unrelated controls with respect to frequency of digital pattern types, position of axial triradius, or type of palmar flexion creases. These findings do not support the hypothesis that children with leukemia have an increased frequency of unusual dermal patterns, but suggest that the dermatoglyphics of leukemic children are not distinctive and therefore have no practical value in the diagnosis of childhood leukemia. Whatever factors are responsible for the development of leukemia in children, these factors do not appear regularly to affect the differentiation of the dermal ridges. PMID:5112119

Developmental lineage priming in Dictyostelium by heterogeneous Ras activation.

PubMed

Chattwood, Alex; Nagayama, Koki; Bolourani, Parvin; Harkin, Lauren; Kamjoo, Marzieh; Weeks, Gerald; Thompson, Christopher R L

2013-11-26

In cell culture, genetically identical cells often exhibit heterogeneous behavior, with only 'lineage primed' cells responding to differentiation inducing signals. It has recently been proposed that such heterogeneity exists during normal embryonic development to allow position independent patterning based on 'salt and pepper' differentiation and sorting out. However, the molecular basis of lineage priming and how it leads to reproducible cell type proportioning are poorly understood. To address this, we employed a novel forward genetic approach in the model organism Dictyostelium discoideum. These studies reveal that the Ras-GTPase regulator gefE is required for normal lineage priming and salt and pepper differentiation. This is because Ras-GTPase activity sets the intrinsic response threshold to lineage specific differentiation signals. Importantly, we show that although gefE expression is uniform, transcription of its target, rasD, is both heterogeneous and dynamic, thus providing a novel mechanism for heterogeneity generation and position-independent differentiation. DOI: http://dx.doi.org/10.7554/eLife.01067.001.

Subtidal circulation patterns in a shallow, highly stratified estuary: Mobile Bay, Alabama

USGS Publications Warehouse

Noble, M.A.; Schroeder, W.W.; Wiseman, W.J.; Ryan, H.F.; Gelfenbaum, G.

1996-01-01

Mobile Bay is a wide (25-50 km), shallow (3 m), highly stratified estuary on the Gulf coast of the United States. In May 1991 a series of instruments that measure near-surface and near-bed current, temperature, salinity, and middepth pressure were deployed for a year-long study of the bay. A full set of measurements were obtained at one site in the lower bay; all but current measurements were obtained at a midbay site. These observations show that the subtidal currents in the lower bay are highly sheared, despite the shallow depth of the estuary. The sheared flow patterns are partly caused by differential forcing from wind stress and river discharge. Two wind-driven flow patterns actually exist in lower Mobile Bay. A barotropic response develops when the difference between near-surface and near-bottom salinity is less than 5 parts per thousand. For stronger salinity gradients the wind-driven currents are larger and the response resembles a baroclinic flow pattern. Currents driven by river flows are sheared and also have a nonlinear response pattern. Only near-surface currents are driven seaward by discharges below 3000 m3/s. At higher discharge rates, surface current variability uncouples from the river flow and the increased discharge rates drive near-bed current seaward. This change in the river-forced flow pattern may be associated with a hydraulic jump in the mouth of the estuary. Copyright 1996 by the American Geophysical Union.

Adaptive potential of northernmost tree populations to climate change, with emphasis on Scots pine (Pinus sylvestris L.).

PubMed

Savolainen, Outi; Kujala, Sonja T; Sokol, Catherina; Pyhäjärvi, Tanja; Avia, Komlan; Knürr, Timo; Kärkkäinen, Katri; Hicks, Sheila

2011-01-01

The adaptive potential of the northernmost Pinus sylvestris L. (and other northern tree) populations is considered by examining first the current patterns of quantitative genetic adaptive traits, which show high population differentiation and clines. We then consider the postglacial history of the populations using both paleobiological and genetic data. The current patterns of diversity at nuclear genes suggest that the traces of admixture are mostly visible in mitochondrial DNA variation patterns. There is little evidence of increased diversity due to admixture between an eastern and western colonization lineage, but no signal of reduced diversity (due to sequential bottlenecks) either. Quantitative trait variation in the north is not associated with the colonizing lineages. The current clines arose rapidly and may be based on standing genetic variation. The initial phenotypic response of Scots pine in the north is predicted to be increased survival and growth. The genetic responses are examined based on quantitative genetic predictions of sustained selection response and compared with earlier simulation results that have aimed at more ecological realism. The phenotypic responses of increased growth and survival reduce the opportunity for selection and delay the evolutionary responses. The lengthening of the thermal growing period also causes selection on the critical photoperiod in the different populations. Future studies should aim at including multiple ecological and genetic factors in evaluating potential responses.

Gene expression profiling of three different stressors in the water flea Daphnia magna.

PubMed

Jansen, Mieke; Vergauwen, Lucia; Vandenbrouck, Tine; Knapen, Dries; Dom, Nathalie; Spanier, Katina I; Cielen, Anke; De Meester, Luc

2013-07-01

Microarrays are an ideal tool to screen for differences in gene expression of thousands of genes simultaneously. However, often commercial arrays are not available. In this study, we performed microarray analyses to evaluate patterns of gene transcription following exposure to two natural and one anthropogenic stressor. cDNA microarrays compiled of three life stage specific and three stressor-specific EST libraries, yielding 1734 different EST sequences, were used. We exposed juveniles of the water flea Daphnia magna for 48, 96 and 144 h to three stressors known to exert strong selection in natural populations of this species i.e. a sublethal concentration of the pesticide carbaryl, infective spores of the endoparasite Pasteuria ramosa, and fish predation risk mimicked by exposure to fish kairomones. A total of 148 gene fragments were differentially expressed compared to the control. Based on a PCA, the exposure treatments were separated into two main groups based on the extent of the transcriptional response: a low and a high (144 h of fish or carbaryl exposure and 96 h of parasite exposure) stress group. Firstly, we observed a general stress-related transcriptional expression profile independent of the treatment characterized by repression of transcripts involved in transcription, translation, signal transduction and energy metabolism. Secondly, we observed treatment-specific responses including signs of migration to deeper water layers in response to fish predation, structural challenge of the cuticle in response to carbaryl exposure, and disturbance of the ATP production in parasite exposure. A third important conclusion is that transcription expression patterns exhibit stress-specific changes over time. Parasite exposure shows the most differentially expressed gene fragments after 96 h. The peak of differentially expressed transcripts came only after 144 h of fish exposure, while carbaryl exposure induced a more stable number of differently expressed gene fragments over time.

EphA2 is an epithelial cell pattern recognition receptor for fungal β-glucans

PubMed Central

Swidergall, Marc; Solis, Norma V.; Lionakis, Michail S.; Filler, Scott G.

2017-01-01

Oral epithelial cells discriminate between pathogenic and non-pathogenic stimuli, and only induce an inflammatory response when they are exposed to high levels of a potentially harmful microorganism. The pattern recognition receptors (PRRs) in epithelial cells that mediate this differential response are poorly understood. Here, we demonstrate that the ephrin type-A receptor 2 (EphA2) is an oral epithelial cell PRR that binds to exposed β-glucans on the surface of the fungal pathogen Candida albicans. Binding of C. albicans to EphA2 on oral epithelial cells activates signal transducer and activator of transcription 3 (Stat3) and mitogen-activated protein kinase signaling in an inoculum-dependent manner, and is required for induction of a pro-inflammatory and antifungal response. EphA2−/− mice have impaired inflammatory responses and reduced IL-17 signaling during oropharyngeal candidiasis, resulting in more severe disease. Our study reveals that EphA2 functions as PRR for β-glucans that senses epithelial cell fungal burden and is required for the maximal mucosal inflammatory response to C. albicans. PMID:29133884

Psychophysiological Response Patterns to Affective Film Stimuli

PubMed Central

Bos, Marieke G. N.; Jentgens, Pia; Beckers, Tom; Kindt, Merel

2013-01-01

Psychophysiological research on emotion utilizes various physiological response measures to index activation of the defense system. Here we tested 1) whether acoustic startle reflex (ASR), skin conductance response (SCR) and heart rate (HR) elicited by highly arousing stimuli specifically reflect a defensive state and 2) the relation between resting heart rate variability (HRV) and affective responding. In a within-subject design, participants viewed film clips with a positive, negative and neutral content. In contrast to SCR and HR, we show that ASR differentiated between negative, neutral and positive states and can therefore be considered as a reliable index of activation of the defense system. Furthermore, resting HRV was associated with affect-modulated characteristics of ASR, but not with SCR or HR. Interestingly, individuals with low-HRV showed less differentiation in ASR between affective states. We discuss the important value of ASR in psychophysiological research on emotion and speculate on HRV as a potential biological marker for demarcating adaptive from maladaptive responding. PMID:23646134

Comparison of particle swarm optimization and differential evolution for aggregators' profit maximization in the demand response system

NASA Astrophysics Data System (ADS)

Wisittipanit, Nuttachat; Wisittipanich, Warisa

2018-07-01

Demand response (DR) refers to changes in the electricity use patterns of end-users in response to incentive payment designed to prompt lower electricity use during peak periods. Typically, there are three players in the DR system: an electric utility operator, a set of aggregators and a set of end-users. The DR model used in this study aims to minimize the operator's operational cost and offer rewards to aggregators, while profit-maximizing aggregators compete to sell DR services to the operator and provide compensation to end-users for altering their consumption profiles. This article presents the first application of two metaheuristics in the DR system: particle swarm optimization (PSO) and differential evolution (DE). The objective is to optimize the incentive payments during various periods to satisfy all stakeholders. The results show that DE significantly outperforms PSO, since it can attain better compensation rates, lower operational costs and higher aggregator profits.

Schedules of electric shock presentation in the behavioral control of imprinted ducklings.

PubMed

Barrett, J E

1972-09-01

The behavioral effects of various schedules of electric shock presentation were investigated during and after the imprinting of Peking ducklings to moving stimuli. The behavior of following a moving imprinted stimulus was differentially controlled by a multiple schedule of punishment and avoidance that respectively suppressed and maintained following behavior. Pole-pecking, reinforced by presentations of the imprinted stimulus, was suppressed by response-produced shock (punishment); various schedules of response-independent shock and delayed punishment had an overall minimal effect. The delivery of response-independent shock in the presence of one of two stimuli, both during and after imprinting, resulted in a marked reduction in choice of the stimulus paired with shock. The experiments provide no support for a differentiation of imprinting from learning on the basis of the behavioral effects of aversive stimuli. Instead, as is the case with other organisms, the schedule under which shock is delivered to imprinted ducklings appears to be an important determinant of the temporal patterning of subsequent behavior.

Twin-Core Fiber-Based Mach Zehnder Interferometer for Simultaneous Measurement of Strain and Temperature

PubMed Central

Kowal, Dominik; Urbanczyk, Waclaw; Mergo, Pawel

2018-01-01

In this paper we present an all-fiber interferometric sensor for the simultaneous measurement of strain and temperature. It is composed of a specially fabricated twin-core fiber spliced between two pieces of a single-mode fiber. Due to the refractive index difference between the two cores in a twin-core fiber, a differential interference pattern is produced at the sensor output. The phase response of the interferometer to strain and temperature is measured in the 850–1250 nm spectral range, showing zero sensitivity to strain at 1000 nm. Due to the significant difference in sensitivities to both parameters, our interferometer is suitable for two-parameter sensing. The simultaneous response of the interferometer to strain and temperature was studied using the two-wavelength interrogation method and a novel approach based on the spectral fitting of the differential phase response. As the latter technique uses all the gathered spectral information, it is more reliable and yields the results with better accuracy. PMID:29558386

Children’s dynamic RSA change during anger and its relations with parenting, temperament, and control of aggression☆

PubMed Central

Miller, Jonas G.; Chocol, Caroline; Nuselovici, Jacob N.; Utendale, William T.; Simard, Melissa; Hastings, Paul D.

2014-01-01

This study examined the moderating effects of child temperament on the association between maternal socialization and 4–6-year-old children’s dynamic respiratory sinus arrhythmia (RSA) change in response to anger-themed emotional materials (N = 180). We used latent growth curve modeling to explore adaptive patterns of dynamic RSA change in response to anger. Greater change in RSA during anger-induction, characterized by more initial RSA suppression and a subsequent return to baseline, was related to children’s better regulation of aggression. For anger-themed materials, low levels of authoritarian parenting predicted more RSA suppression and recovery for more anger-prone children, whereas more authoritative parenting predicted more RSA suppression and recovery for less anger-prone children. These findings suggest that children’s adaptive patterns of dynamic RSA change can be characterized by latent growth curve modeling, and that these patterns may be differentially shaped by parent socialization experiences as a function of child temperament. PMID:23274169

Children's dynamic RSA change during anger and its relations with parenting, temperament, and control of aggression.

PubMed

Miller, Jonas G; Chocol, Caroline; Nuselovici, Jacob N; Utendale, William T; Simard, Melissa; Hastings, Paul D

2013-02-01

This study examined the moderating effects of child temperament on the association between maternal socialization and 4-6-year-old children's dynamic respiratory sinus arrhythmia (RSA) change in response to anger-themed emotional materials (N=180). We used latent growth curve modeling to explore adaptive patterns of dynamic RSA change in response to anger. Greater change in RSA during anger-induction, characterized by more initial RSA suppression and a subsequent return to baseline, was related to children's better regulation of aggression. For anger-themed materials, low levels of authoritarian parenting predicted more RSA suppression and recovery for more anger-prone children, whereas more authoritative parenting predicted more RSA suppression and recovery for less anger-prone children. These findings suggest that children's adaptive patterns of dynamic RSA change can be characterized by latent growth curve modeling, and that these patterns may be differentially shaped by parent socialization experiences as a function of child temperament. Copyright © 2013 Elsevier B.V. All rights reserved.

A Bayesian Model of Category-Specific Emotional Brain Responses

PubMed Central

Wager, Tor D.; Kang, Jian; Johnson, Timothy D.; Nichols, Thomas E.; Satpute, Ajay B.; Barrett, Lisa Feldman

2015-01-01

Understanding emotion is critical for a science of healthy and disordered brain function, but the neurophysiological basis of emotional experience is still poorly understood. We analyzed human brain activity patterns from 148 studies of emotion categories (2159 total participants) using a novel hierarchical Bayesian model. The model allowed us to classify which of five categories—fear, anger, disgust, sadness, or happiness—is engaged by a study with 66% accuracy (43-86% across categories). Analyses of the activity patterns encoded in the model revealed that each emotion category is associated with unique, prototypical patterns of activity across multiple brain systems including the cortex, thalamus, amygdala, and other structures. The results indicate that emotion categories are not contained within any one region or system, but are represented as configurations across multiple brain networks. The model provides a precise summary of the prototypical patterns for each emotion category, and demonstrates that a sufficient characterization of emotion categories relies on (a) differential patterns of involvement in neocortical systems that differ between humans and other species, and (b) distinctive patterns of cortical-subcortical interactions. Thus, these findings are incompatible with several contemporary theories of emotion, including those that emphasize emotion-dedicated brain systems and those that propose emotion is localized primarily in subcortical activity. They are consistent with componential and constructionist views, which propose that emotions are differentiated by a combination of perceptual, mnemonic, prospective, and motivational elements. Such brain-based models of emotion provide a foundation for new translational and clinical approaches. PMID:25853490

Correlating chemical sensitivity and basal gene expression reveals mechanism of action | Office of Cancer Genomics

Cancer.gov

Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity across many cell lines to illuminate the actions of compounds whose MoA are unknown.

Comparative Response of the Hepatic Transcriptomes of Domesticated and Wild Turkey to Aflatoxin B₁.

PubMed

Reed, Kent M; Mendoza, Kristelle M; Abrahante, Juan E; Coulombe, Roger A

2018-01-13

The food-borne mycotoxin aflatoxin B₁ (AFB₁) poses a significant risk to poultry, which are highly susceptible to its hepatotoxic effects. Domesticated turkeys ( Meleagris gallopavo ) are especially sensitive, whereas wild turkeys ( M. g. silvestris ) are more resistant. AFB₁ toxicity entails bioactivation by hepatic cytochrome P450s to the electrophilic exo-AFB₁-8,9-epoxide (AFBO). Domesticated turkeys lack functional hepatic GST-mediated detoxification of AFBO, and this is largely responsible for the differences in resistance between turkey types. This study was designed to characterize transcriptional changes induced in turkey livers by AFB₁, and to contrast the response of domesticated (susceptible) and wild (more resistant) birds. Gene expression responses to AFB₁ were examined using RNA-sequencing. Statistically significant differences in gene expression were observed among treatment groups and between turkey types. Expression analysis identified 4621 genes with significant differential expression (DE) in AFB₁-treated birds compared to controls. Characterization of DE transcripts revealed genes dis-regulated in response to toxic insult with significant association of Phase I and Phase II genes and others important in cellular regulation, modulation of apoptosis, and inflammatory responses. Constitutive expression of GSTA3 was significantly higher in wild birds and was significantly higher in AFB₁-treated birds when compared to controls for both genetic groups. This pattern was also observed by qRT-PCR in other wild and domesticated turkey strains. Results of this study emphasize the differential response of these genetically distinct birds, and identify genes and pathways that are differentially altered in aflatoxicosis.

Epigenetic and genetic variation among three separate introductions of the house sparrow (Passer domesticus) into Australia

PubMed Central

Schrey, A.; Ragsdale, A.; Griffith, S. C.

2018-01-01

Invasive populations are often associated with low levels of genetic diversity owing to population bottlenecks at the initial stages of invasion. Despite this, the ability of invasive species to adapt rapidly in response to novel environments is well documented. Epigenetic mechanisms have recently been proposed to facilitate the success of invasive species by compensating for reduced levels of genetic variation. Here, we use methylation sensitive-amplification fragment length polymorphism and microsatellite analyses to compare levels of epigenetic and genetic diversity and differentiation across 15 sites in the introduced Australian house sparrow population. We find patterns of epigenetic and genetic differentiation that are consistent with historical descriptions of three distinct, introductions events. However unlike genetic differentiation, epigenetic differentiation was higher among sample sites than among invasion clusters, suggesting that patterns of epigenetic variation are more strongly influenced by local environmental stimuli or sequential founder events than the initial diversity in the introduction population. Interestingly, we fail to detect correlations between pairwise site comparisons of epigenetic and genetic differentiation, suggesting that some of the observed epigenetic variation has arisen independently of genetic variation. We also fail to detect the potentially compensatory relationship between epigenetic and genetic diversity that has been detected in a more recent house sparrow invasion in Africa. We discuss the potential for this relationship to be obscured by recovered genetic diversity in more established populations, and highlight the importance of incorporating introduction history into population-wide epigenetic analyses. PMID:29765671

Mapping gene expression patterns during myeloid differentiation using the EML hematopoietic progenitor cell line.

PubMed

Du, Yang; Campbell, Janee L; Nalbant, Demet; Youn, Hyewon; Bass, Ann C Hughes; Cobos, Everardo; Tsai, Schickwann; Keller, Jonathan R; Williams, Simon C

2002-07-01

The detailed examination of the molecular events that control the early stages of myeloid differentiation has been hampered by the relative scarcity of hematopoietic stem cells and the lack of suitable cell line models. In this study, we examined the expression of several myeloid and nonmyeloid genes in the murine EML hematopoietic stem cell line. Expression patterns for 19 different genes were examined by Northern blotting and RT-PCR in RNA samples from EML, a variety of other immortalized cell lines, and purified murine hematopoietic stem cells. Representational difference analysis (RDA) was performed to identify differentially expressed genes in EML. Expression patterns of genes encoding transcription factors (four members of the C/EBP family, GATA-1, GATA-2, PU.1, CBFbeta, SCL, and c-myb) in EML were examined and were consistent with the proposed functions of these proteins in hematopoietic differentiation. Expression levels of three markers of terminal myeloid differentiation (neutrophil elastase, proteinase 3, and Mac-1) were highest in EML cells at the later stages of differentiation. In a search for genes that were differentially expressed in EML cells during myeloid differentiation, six cDNAs were isolated. These included three known genes (lysozyme, histidine decarboxylase, and tryptophan hydroxylase) and three novel genes. Expression patterns of known genes in differentiating EML cells accurately reflected their expected expression patterns based on previous studies. The identification of three novel genes, two of which encode proteins that may act as regulators of hematopoietic differentiation, suggests that EML is a useful model system for the molecular analysis of hematopoietic differentiation.

Transcriptome-wide analysis of differential gene expression in response to light:dark cycles in a model cnidarian.

PubMed

Leach, W B; Macrander, J; Peres, R; Reitzel, A M

2018-06-01

Animals respond to diurnal shifts in their environment with a combination of behavioral, physiological, and molecular changes to synchronize with regularly-timed external cues. Reproduction, movement, and metabolism in cnidarians have all been shown to be regulated by diurnal lighting, but the molecular mechanisms that may be responsible for these phenotypes remain largely unknown. The starlet sea anemone, Nematostella vectensis, has oscillating patterns of locomotion and respiration, as well as the molecular components of a putative circadian clock that may provide a mechanism for these light-induced responses. Here, we compare transcriptomic responses of N. vectensis when cultured under a diurnal lighting condition (12 h light: 12 h dark) with sea anemones cultured under constant darkness for 20 days. More than 3,000 genes (~13% of transcripts) had significant differences in expression between light and dark, with most genes having higher expression in the photoperiod. Following removal of the light cue 678 genes lost differential expression, suggesting that light-entrained gene expression by the circadian clock has temporal limits. Grouping of genes differentially expressed in light:dark conditions showed that cell cycle and transcription maintained diel expression in the absence of light, while many of the genes related to metabolism, antioxidants, immunity, and signal transduction lost differential expression without a light cue. Our data highlight the importance of diel light cycles on circadian mechanisms in this species, prompting new hypotheses for the role of photoreception in major biological processes, e.g., metabolism, immunity. Copyright © 2018 Elsevier Inc. All rights reserved.

Prediction of response to preoperative chemoradiotherapy and establishment of individualized therapy in advanced rectal cancer.

PubMed

Nakao, Toshihiro; Iwata, Takashi; Hotchi, Masanori; Yoshikawa, Kozo; Higashijima, Jun; Nishi, Masaaki; Takasu, Chie; Eto, Shohei; Teraoku, Hiroki; Shimada, Mitsuo

2015-10-01

Preoperative chemoradiotherapy (CRT) has become the standard treatment for patients with locally advanced rectal cancer. However, no specific biomarker has been identified to predict a response to preoperative CRT. The aim of the present study was to assess the gene expression patterns of patients with advanced rectal cancer to predict their responses to preoperative CRT. Fifty-nine rectal cancer patients were subjected to preoperative CRT. Patients were randomly assigned to receive CRT with tegafur/gimeracil/oteracil (S-1 group, n=30) or tegafur-uracil (UFT group, n=29). Gene expression changes were studied with cDNA and miRNA microarray. The association between gene expression and response to CRT was evaluated. cDNA microarray showed that 184 genes were significantly differentially expressed between the responders and the non‑responders in the S-1 group. Comparatively, 193 genes were significantly differentially expressed in the responders in the UFT group. TBX18 upregulation was common to both groups whereas BTNL8, LOC375010, ADH1B, HRASLS2, LOC284232, GCNT3 and ALDH1A2 were significantly differentially lower in both groups when compared with the non-responders. Using miRNA microarray, we found that 7 and 16 genes were significantly differentially expressed between the responders and non-responders in the S-1 and UFT groups, respectively. miR-223 was significantly higher in the responders in the S-1 group and tended to be higher in the responders in the UFT group. The present study identified several genes likely to be useful for establishing individualized therapies for patients with rectal cancer.

Simple agarose micro-confinement array and machine-learning-based classification for analyzing the patterned differentiation of mesenchymal stem cells

PubMed Central

Sato, Asako; Vogel, Viola; Tanaka, Yo

2017-01-01

The geometrical confinement of small cell colonies gives differential cues to cells sitting at the periphery versus the core. To utilize this effect, for example to create spatially graded differentiation patterns of human mesenchymal stem cells (hMSCs) in vitro or to investigate underpinning mechanisms, the confinement needs to be robust for extended time periods. To create highly repeatable micro-fabricated structures for cellular patterning and high-throughput data mining, we employed here a simple casting method to fabricate more than 800 adhesive patches confined by agarose micro-walls. In addition, a machine learning based image processing software was developed (open code) to detect the differentiation patterns of the population of hMSCs automatically. Utilizing the agarose walls, the circular patterns of hMSCs were successfully maintained throughout 15 days of cell culture. After staining lipid droplets and alkaline phosphatase as the markers of adipogenic and osteogenic differentiation, respectively, the mega-pixels of RGB color images of hMSCs were processed by the software on a laptop PC within several minutes. The image analysis successfully showed that hMSCs sitting on the more central versus peripheral sections of the adhesive circles showed adipogenic versus osteogenic differentiation as reported previously, indicating the compatibility of patterned agarose walls to conventional microcontact printing. In addition, we found a considerable fraction of undifferentiated cells which are preferentially located at the peripheral part of the adhesive circles, even in differentiation-inducing culture media. In this study, we thus successfully demonstrated a simple framework for analyzing the patterned differentiation of hMSCs in confined microenvironments, which has a range of applications in biology, including stem cell biology. PMID:28380036

The Effects of Topographical Patterns and Sizes on Neural Stem Cell Behavior

PubMed Central

Qi, Lin; Li, Ning; Huang, Rong; Song, Qin; Wang, Long; Zhang, Qi; Su, Ruigong; Kong, Tao; Tang, Mingliang; Cheng, Guosheng

2013-01-01

Engineered topographical manipulation, a paralleling approach with conventional biochemical cues, has recently attracted the growing interests in utilizations to control stem cell fate. In this study, effects of topological parameters, pattern and size are emphasized on the proliferation and differentiation of adult neural stem cells (ANSCs). We fabricate micro-scale topographical Si wafers with two different feature sizes. These topographical patterns present linear micro-pattern (LMP), circular micro-pattern (CMP) and dot micro-pattern (DMP). The results show that the three topography substrates are suitable for ANSC growth, while they all depress ANSC proliferation when compared to non-patterned substrates (control). Meanwhile, LMP and CMP with two feature sizes can both significantly enhance ANSC differentiation to neurons compared to control. The smaller the feature size is, the better upregulation applies to ANSC for the differentiated neurons. The underlying mechanisms of topography-enhanced neuronal differentiation are further revealed by directing suppression of mitogen-activated protein kinase/extracellular signaling-regulated kinase (MAPK/Erk) signaling pathway in ANSC using U0126, known to inhibit the activation of Erk. The statistical results suggest MAPK/Erk pathway is partially involved in topography-induced differentiation. These observations provide a better understanding on the different roles of topographical cues on stem cell behavior, especially on the selective differentiation, and facilitate to advance the field of stem cell therapy. PMID:23527077

Global gene expression during stringent response in Corynebacterium glutamicum in presence and absence of the rel gene encoding (p)ppGpp synthase

PubMed Central

Brockmann-Gretza, Olaf; Kalinowski, Jörn

2006-01-01

Background The stringent response is the initial reaction of microorganisms to nutritional stress. During stringent response the small nucleotides (p)ppGpp act as global regulators and reprogram bacterial transcription. In this work, the genetic network controlled by the stringent response was characterized in the amino acid-producing Corynebacterium glutamicum. Results The transcriptome of a C. glutamicum rel gene deletion mutant, unable to synthesize (p)ppGpp and to induce the stringent response, was compared with that of its rel-proficient parent strain by microarray analysis. A total of 357 genes were found to be transcribed differentially in the rel-deficient mutant strain. In a second experiment, the stringent response was induced by addition of DL-serine hydroxamate (SHX) in early exponential growth phase. The time point of the maximal effect on transcription was determined by real-time RT-PCR using the histidine and serine biosynthetic genes. Transcription of all of these genes reached a maximum at 10 minutes after SHX addition. Microarray experiments were performed comparing the transcriptomes of SHX-induced cultures of the rel-proficient strain and the rel mutant. The differentially expressed genes were grouped into three classes. Class A comprises genes which are differentially regulated only in the presence of an intact rel gene. This class includes the non-essential sigma factor gene sigB which was upregulated and a large number of genes involved in nitrogen metabolism which were downregulated. Class B comprises genes which were differentially regulated in response to SHX in both strains, independent of the rel gene. A large number of genes encoding ribosomal proteins fall into this class, all being downregulated. Class C comprises genes which were differentially regulated in response to SHX only in the rel mutant. This class includes genes encoding putative stress proteins and global transcriptional regulators that might be responsible for the complex transcriptional patterns detected in the rel mutant when compared directly with its rel-proficient parent strain. Conclusion In C. glutamicum the stringent response enfolds a fast answer to an induced amino acid starvation on the transcriptome level. It also showed some significant differences to the transcriptional reactions occuring in Escherichia coli and Bacillus subtilis. Notable are the rel-dependent regulation of the nitrogen metabolism genes and the rel-independent regulation of the genes encoding ribosomal proteins. PMID:16961923

Testing differential susceptibility: Plasticity genes, the social environment, and their interplay in adolescent response inhibition.

PubMed

Richards, Jennifer S; Arias Vásquez, Alejandro; van Rooij, Daan; van der Meer, Dennis; Franke, Barbara; Hoekstra, Pieter J; Heslenfeld, Dirk J; Oosterlaan, Jaap; Faraone, Stephen V; Hartman, Catharina A; Buitelaar, Jan K

2017-06-01

Impaired inhibitory control is a key feature of attention-deficit/hyperactivity disorder (ADHD). We investigated gene-environment interaction (GxE) as a possible contributing factor to response inhibition variation in context of the differential susceptibility theory. This states individuals carrying plasticity gene variants will be more disadvantaged in negative, but more advantaged in positive environments. Behavioural and neural measures of response inhibition were assessed during a Stop-signal task in participants with (N = 197) and without (N = 295) ADHD, from N = 278 families (age M = 17.18, SD =3.65). We examined GxE between candidate plasticity genes (DAT1, 5-HTT, DRD4) and social environments (maternal expressed emotion, peer affiliation). A DRD4 × Positive peer affiliation interaction was found on the right fusiform gyrus (rFG) activation during successful inhibition. Further, 5-HTT short allele carriers showed increased rFG activation during failed inhibitions. Maternal warmth and positive peer affiliation were positively associated with right inferior frontal cortex activation during successful inhibition. Deviant peer affiliation was positively related to the error rate. While a pattern of differential genetic susceptibility was found, more clarity on the role of the FG during response inhibition is warranted before firm conclusions can be made. Positive and negative social environments were related to inhibitory control. This extends previous research emphasizing adverse environments.

Differentially Expressed microRNAs and Target Genes Associated with Plastic Internode Elongation in Alternanthera philoxeroides in Contrasting Hydrological Habitats

PubMed Central

Li, Gengyun; Deng, Ying; Geng, Yupeng; Zhou, Chengchuan; Wang, Yuguo; Zhang, Wenju; Song, Zhiping; Gao, Lexuan; Yang, Ji

2017-01-01

Phenotypic plasticity is crucial for plants to survive in changing environments. Discovering microRNAs, identifying their targets and further inferring microRNA functions in mediating plastic developmental responses to environmental changes have been a critical strategy for understanding the underlying molecular mechanisms of phenotypic plasticity. In this study, the dynamic expression patterns of microRNAs under contrasting hydrological habitats in the amphibious species Alternanthera philoxeroides were identified by time course expression profiling using high-throughput sequencing technology. A total of 128 known and 18 novel microRNAs were found to be differentially expressed under contrasting hydrological habitats. The microRNA:mRNA pairs potentially associated with plastic internode elongation were identified by integrative analysis of microRNA and mRNA expression profiles, and were validated by qRT-PCR and 5′ RLM-RACE. The results showed that both the universal microRNAs conserved across different plants and the unique microRNAs novelly identified in A. philoxeroides were involved in the responses to varied water regimes. The results also showed that most of the differentially expressed microRNAs were transiently up-/down-regulated at certain time points during the treatments. The fine-scale temporal changes in microRNA expression highlighted the importance of time-series sampling in identifying stress-responsive microRNAs and analyzing their role in stress response/tolerance. PMID:29259617

The Differentiation of Response Numerosities in the Pigeon

PubMed Central

Machado, Armando; Rodrigues, Paulo

2007-01-01

Two experiments examined how pigeons differentiate response patterns along the dimension of number. In Experiment 1, 5 pigeons received food after pecking the left key at least N times and then switching to the right key (Mechner’s Fixed Consecutive Number schedule). Parameter N varied across conditions from 4 to 32. Results showed that run length on the left key followed a normal distribution whose mean and standard deviation increased linearly with N; the coefficient of variation approached a constant value (the scalar property). In Experiment 2, 4 pigeons received food with probability p for pecking the left key exactly four times and then switching. If that did not happen, the pigeons still could receive food by returning to the left key and pecking it for a total of at least 16 times and then switching. Parameter p varied across conditions from 1.0 to .25. Results showed that when p = 1.0 or p = .5, pigeons learned two response numerosities within the same condition. When p = .25, each pigeon adapted to the schedule differently. Two of them emitted first runs well described by a mixture of two normal distributions, one with mean close to 4 and the other with mean close to 16 pecks. A mathematical model for the differentiation of response numerosity in Fixed Consecutive Number schedules is proposed. PMID:17970413

Patterns of sexual arousal in homosexual, bisexual, and heterosexual men.

PubMed

Cerny, Jerome A; Janssen, Erick

2011-08-01

The purpose of this study was to determine if self-identified bisexual, heterosexual, and homosexual men show differential genital and subjective arousal patterns to video presentations of bisexual, heterosexual, male homosexual, and lesbian sexual interactions. It was predicted that, relative to heterosexual and homosexual stimuli, bisexual men would show the highest levels of sexual arousal to bisexual erotic material, while this stimulus would induce relatively low levels of response in heterosexual and homosexual men. A sample of 59 men (19 homosexual, 13 bisexual, and 27 heterosexual) were presented with a series of 4-min sexual videos while their genital and subjective sexual responses were measured continuously. Bisexual men did not differ significantly in their responses to male homosexual stimuli (depicting men engaging in sex) from homosexual men, and they did not differ significantly in their responses to heterosexual (depicting two women, without same-sex contact, engaged in sex with a man) and lesbian (depicting women engaging in sex) stimuli from heterosexual men. However, bisexual men displayed significantly higher levels of both genital and subjective sexual arousal to a bisexual stimulus (depicting a man engaged in sex with both a man and a woman) than either homosexual or heterosexual men. The findings of this study indicate that bisexuality in men is associated with a unique and specific pattern of sexual arousal.

Particles from wood smoke and traffic induce differential pro-inflammatory response patterns in co-cultures

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

Kocbach, Anette; Herseth, Jan Inge; Lag, Marit

2008-10-15

The inflammatory potential of particles from wood smoke and traffic has not been well elucidated. In this study, a contact co-culture of monocytes and pneumocytes was exposed to 10-40 {mu}g/cm{sup 2} of particles from wood smoke and traffic for 12, 40 and 64 h to determine their influence on pro-inflammatory cytokine release (TNF-{alpha}, IL-1, IL-6, IL-8) and viability. To investigate the role of organic constituents in cytokine release the response to particles, their organic extracts and the washed particles were compared. Antagonists were used to investigate source-dependent differences in intercellular signalling (TNF-{alpha}, IL-1). The cytotoxicity was low after exposure tomore » particles from both sources. However, wood smoke, and to a lesser degree traffic-derived particles, induced a reduction in cell number, which was associated with the organic fraction. The release of pro-inflammatory cytokines was similar for both sources after 12 h, but traffic induced a greater release than wood smoke particles with increasing exposure time. The organic fraction accounted for the majority of the cytokine release induced by wood smoke, whereas the washed traffic particles induced a stronger response than the corresponding organic extract. TNF-{alpha} and IL-1 antagonists reduced the release of IL-8 induced by particles from both sources. In contrast, the IL-6 release was only reduced by the IL-1 antagonist during exposure to traffic-derived particles. In summary, particles from wood smoke and traffic induced differential pro-inflammatory response patterns with respect to cytokine release and cell number. Moreover, the influence of the organic particle fraction and intercellular signalling on the pro-inflammatory response seemed to be source-dependent.« less

Wounding, insect chewing and phloem sap feeding differentially alter the leaf proteome of potato, Solanum tuberosum L.

PubMed Central

2012-01-01

Background Various factors shape the response of plants to herbivorous insects, including wounding patterns, specific chemical effectors and feeding habits of the attacking herbivore. Here we performed a comparative proteomic analysis of the plant's response to wounding and herbivory, using as a model potato plants (Solanum tuberosum L.) subjected to mechanical wounding, defoliation by the Colorado potato beetle Leptinotarsa decemlineata Say, or phloem sap feeding by the potato aphid Macrosiphum euphorbiae Thomas. Results Out of ~500 leaf proteins monitored by two-dimensional gel electrophoresis (2-DE), 31 were up- or downregulated by at least one stress treatment compared to healthy control plants. Of these proteins, 29 were regulated by beetle chewing, 8 by wounding and 8 by aphid feeding. Some proteins were up- or downregulated by two different treatments, while others showed diverging expression patterns in response to different treatments. A number of modulated proteins identified by mass spectrometry were typical defense proteins, including wound-inducible protease inhibitors and pathogenesis-related proteins. Proteins involved in photosynthesis were also modulated, notably by potato beetle feeding inducing a strong decrease of some photosystem I proteins. Quantitative RT PCR assays were performed with nucleotide primers for photosynthesis-related proteins to assess the impact of wounding and herbivory at the gene level. Whereas different, sometimes divergent, responses were observed at the proteome level in response to wounding and potato beetle feeding, downregulating effects were systematically observed for both treatments at the transcriptional level. Conclusions These observations illustrate the differential impacts of wounding and insect herbivory on defense- and photosynthesis-related components of the potato leaf proteome, likely associated with the perception of distinct physical and chemical cues in planta. PMID:23268880

Initial leukemic gene expression profiles of patients with poor in vivo prednisone response are similar to those of blasts persisting under prednisone treatment in childhood acute lymphoblastic leukemia.

PubMed

Cario, Gunnar; Fetz, Andrea; Bretscher, Christian; Möricke, Anja; Schrauder, Andre; Stanulla, Martin; Schrappe, Martin

2008-09-01

Response to initial glucocorticoid (GC) treatment is a strong prognostic factor in childhood acute lymphoblastic leukemia (ALL). Patients with a poor prednisone response (PPR) have a poor event-free survival as compared to those with a good prednisone response (PGR). Causes of prednisone resistance are still not well understood. We hypothesized that GC resistance is an intrinsic feature of ALL cells which is reflected in the gene expression pattern and analyzed genome-wide gene expression using microarrays. A case-control study was performed comparing gene expression profiles from initial ALL samples of 20 patients with PPR and those of 20 patients with PGR. Differential gene expression of a subset of genes was confirmed by real-time quantitative polymerase chain reaction analysis and validation was performed in a second independent patient sample (n=20). We identified 121 genes that clearly distinguished prednisone-resistant from sensitive ALL samples (FDR<5%, fold change>or=1.5). Differential gene expression of 21 of these genes could be validated in a second independent set. Of importance, there was a remarkable concordance of genes identified by comparing expression signatures of PPR and PGR cells at diagnosis and those previously described to be up- or downregulated in leukemic cells persisting under GC treatment. Thus, GC resistance seems at least in part to be an intrinsic feature of leukemic cells. Leukemic cells of patients with PPR are characterized by gene expression pattern which are similar to those of resistant cells persisting under glucocorticoid treatment.

Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes.

PubMed

Pondman, Kirsten M; Pednekar, Lina; Paudyal, Basudev; Tsolaki, Anthony G; Kouser, Lubna; Khan, Haseeb A; Shamji, Mohamed H; Ten Haken, Bennie; Stenbeck, Gudrun; Sim, Robert B; Kishore, Uday

2015-11-01

Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Multiple environmental factors regulate the expression of the carbohydrate-selective OprB porin of Pseudomonas aeruginosa.

PubMed

Adewoye, L O; Worobec, E A

1999-12-01

In response to low extracellular glucose concentration, Pseudomonas aeruginosa induces the expression of the outer membrane carbohydrate-selective OprB porin. The promoter region of the oprB gene was cloned into a lacZ transcriptional fusion vector, and the construct was mobilized into P. aeruginosa OprB-deficient strain, WW100, to evaluate additional environmental factors that influence OprB porin gene expression. Growth temperature, pH of the growth medium, salicylate concentration, and carbohydrate source were found to differentially influence porin expression. This expression pattern was compared to those of whole-cell [14C]glucose uptake under conditions of high osmolarity, ionicity, variable pH, growth temperatures, and carbohydrate source. These studies revealed that the high-affinity glucose transport genes are down-regulated by salicylic acid, differentially regulated by pH and temperature, and are specifically responsive to exogenous glucose induction.

Dynamics of γ-tubulin cytoskeleton in HL-60 leukemia cells undergoing differentiation and apoptosis by all-trans retinoic acid.

PubMed

Shariftabrizi, Ahmad; Ahmadian, Shahin; Pazhang, Yaghub

2012-02-01

Microtubules are important components of the cell cytoskeleton, participating in protein localization and cell signaling. The capacity of leukemia cells to re-organize their microtubules is considered an integral part of differentiation in these cells in order to become mature granulocytes through treatment with all-trans retinoic acid (ATRA), an established drug for treating acute promyelocytic leukemia. In this study we examined γ-, α- and acetylated-α-tubulin content, their patterns of distribution in the cytoplasm, and the potency of centrosomes in re-organizing microtubules in different stages of ATRA-induced differentiation and apoptosis of the HL-60 cell line. The γ-tubulin content was dramatically increased following differentiation of HL-60 cells, and was then decreased after apoptosis. We also found that γ-tubulin had a diffuse, cytoplasmic pattern following apoptosis compared to the focal, centrosomal accumulation of γ-tubulin in differentiated cells. Differentiated cells had the ability to re-organize their microtubule network following nocodazole challenge testing, whereas undifferentiated cells did not show a similar ability. α-tubulin was more regularly organized in differentiated cells, and did not reveal any specific pattern of polymerization in apoptotic cells. Acetylated-α-tubulin generally followed the same organization patterns after differentiation, as that which occurred for α-tubulin. Our data is suggestive of a centrosomal and organized nucleation pattern of microtubules in HL-60 cells following differentiation, possibly mediated through up-regulation of γ-tubulin.

You're Just Like Your Dad: Intergenerational Patterns of Differential Treatment of Siblings.

PubMed

Jensen, Alexander C; Whiteman, Shawn D; Rand, Joseph S; Fingerman, Karen L

2017-10-01

Past work highlights that parents' differential treatment has implications for offspring's mental and relational health across the life course. Although the current body of literature has examined offspring- and parent-level correlates of differential treatment, research has yet to consider whether and how patterns of differential treatment are transmitted across generations. As part of a two-wave longitudinal study of 157 families, both grandparents (M age = 76.50 years, SD = 6.20) and parents (M age = 51.10 years, SD = 4.41) reported on differential treatment of their own offspring at both phases. A series of residualized change models revealed support for both continuity and compensation hypotheses. Middle-aged parents tended to model the patterns of differential treatment exhibited by their fathers, but middle-aged men who experienced more differential treatment from their own parents in recent years tended to subsequently exhibit lower levels of differential treatment to their offspring. These findings suggest that patterns of differential treatment both continue and diverge across generations, and those patterns vary by gender. On a broader level, these results also suggest that siblings not only impact one another's development, but in adulthood, they may indirectly influence their nieces' and nephews' development by virtue of their influence on their siblings' parenting. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Shear-induced endothelial mechanotransduction: the interplay between reactive oxygen species (ROS) and nitric oxide (NO) and the pathophysiological implications

PubMed Central

2014-01-01

Hemodynamic shear stress, the blood flow-generated frictional force acting on the vascular endothelial cells, is essential for endothelial homeostasis under normal physiological conditions. Mechanosensors on endothelial cells detect shear stress and transduce it into biochemical signals to trigger vascular adaptive responses. Among the various shear-induced signaling molecules, reactive oxygen species (ROS) and nitric oxide (NO) have been implicated in vascular homeostasis and diseases. In this review, we explore the molecular, cellular, and vascular processes arising from shear-induced signaling (mechanotransduction) with emphasis on the roles of ROS and NO, and also discuss the mechanisms that may lead to excessive vascular remodeling and thus drive pathobiologic processes responsible for atherosclerosis. Current evidence suggests that NADPH oxidase is one of main cellular sources of ROS generation in endothelial cells under flow condition. Flow patterns and magnitude of shear determine the amount of ROS produced by endothelial cells, usually an irregular flow pattern (disturbed or oscillatory) producing higher levels of ROS than a regular flow pattern (steady or pulsatile). ROS production is closely linked to NO generation and elevated levels of ROS lead to low NO bioavailability, as is often observed in endothelial cells exposed to irregular flow. The low NO bioavailability is partly caused by the reaction of ROS with NO to form peroxynitrite, a key molecule which may initiate many pro-atherogenic events. This differential production of ROS and RNS (reactive nitrogen species) under various flow patterns and conditions modulates endothelial gene expression and thus results in differential vascular responses. Moreover, ROS/RNS are able to promote specific post-translational modifications in regulatory proteins (including S-glutathionylation, S-nitrosylation and tyrosine nitration), which constitute chemical signals that are relevant in cardiovascular pathophysiology. Overall, the dynamic interplay between local hemodynamic milieu and the resulting oxidative and S-nitrosative modification of regulatory proteins is important for ensuing vascular homeostasis. Based on available evidence, it is proposed that a regular flow pattern produces lower levels of ROS and higher NO bioavailability, creating an anti-atherogenic environment. On the other hand, an irregular flow pattern results in higher levels of ROS and yet lower NO bioavailability, thus triggering pro-atherogenic effects. PMID:24410814

Comparative Digital Gene Expression Analysis of the Arabidopsis Response to Volatiles Emitted by Bacillus amyloliquefaciens

PubMed Central

Hao, Hai-Ting; Zhao, Xia; Shang, Qian-Han; Wang, Yun; Guo, Zhi-Hong; Zhang, Yu-Bao; Xie, Zhong-Kui; Wang, Ruo-Yu

2016-01-01

Some plant growth-promoting rhizobacteria (PGPR) regulated plant growth and elicited plant basal immunity by volatiles. The response mechanism to the Bacillus amyloliquefaciens volatiles in plant has not been well studied. We conducted global gene expression profiling in Arabidopsis after treatment with Bacillus amyloliquefaciens FZB42 volatiles by Illumina Digital Gene Expression (DGE) profiling of different growth stages (seedling and mature) and tissues (leaves and roots). Compared with the control, 1,507 and 820 differentially expressed genes (DEGs) were identified in leaves and roots at the seedling stage, respectively, while 1,512 and 367 DEGs were identified in leaves and roots at the mature stage. Seventeen genes with different regulatory patterns were validated using quantitative RT-PCR. Numerous DEGs were enriched for plant hormones, cell wall modifications, and protection against stress situations, which suggests that volatiles have effects on plant growth and immunity. Moreover, analyzes of transcriptome difference in tissues and growth stage using DGE profiling showed that the plant response might be tissue-specific and/or growth stage-specific. Thus, genes encoding flavonoid biosynthesis were downregulated in leaves and upregulated in roots, thereby indicating tissue-specific responses to volatiles. Genes related to photosynthesis were downregulated at the seedling stage and upregulated at the mature stage, respectively, thereby suggesting growth period-specific responses. In addition, the emission of bacterial volatiles significantly induced killing of cells of other organism pathway with up-regulated genes in leaves and the other three pathways (defense response to nematode, cell morphogenesis involved in differentiation and trichoblast differentiation) with up-regulated genes were significantly enriched in roots. Interestingly, some important alterations in the expression of growth-related genes, metabolic pathways, defense response to biotic stress and hormone-related genes were firstly founded response to FZB42 volatiles. PMID:27513952

Microarray Detection Call Methodology as a Means to Identify and Compare Transcripts Expressed within Syncytial Cells from Soybean (Glycine max) Roots Undergoing Resistant and Susceptible Reactions to the Soybean Cyst Nematode (Heterodera glycines)

PubMed Central

Klink, Vincent P.; Overall, Christopher C.; Alkharouf, Nadim W.; MacDonald, Margaret H.; Matthews, Benjamin F.

2010-01-01

Background. A comparative microarray investigation was done using detection call methodology (DCM) and differential expression analyses. The goal was to identify genes found in specific cell populations that were eliminated by differential expression analysis due to the nature of differential expression methods. Laser capture microdissection (LCM) was used to isolate nearly homogeneous populations of plant root cells. Results. The analyses identified the presence of 13,291 transcripts between the 4 different sample types. The transcripts filtered down into a total of 6,267 that were detected as being present in one or more sample types. A comparative analysis of DCM and differential expression methods showed a group of genes that were not differentially expressed, but were expressed at detectable amounts within specific cell types. Conclusion. The DCM has identified patterns of gene expression not shown by differential expression analyses. DCM has identified genes that are possibly cell-type specific and/or involved in important aspects of plant nematode interactions during the resistance response, revealing the uniqueness of a particular cell population at a particular point during its differentiation process. PMID:20508855

Patterns of Genetic Variation across Altitude in Three Plant Species of Semi-Dry Grasslands

PubMed Central

Hahn, Thomas; Kettle, Chris J.; Ghazoul, Jaboury; Frei, Esther R.; Matter, Philippe; Pluess, Andrea R.

2012-01-01

Background Environmental gradients caused by altitudinal gradients may affect genetic variation within and among plant populations and inbreeding within populations. Populations in the upper range periphery of a species may be important source populations for range shifts to higher altitude in response to climate change. In this study we investigate patterns of population genetic variation at upper peripheral and lower more central altitudes in three common plant species of semi-dry grasslands in montane landscapes. Methodology/Principal Findings In Briza media, Trifolium montanum and Ranunculus bulbosus genetic diversity, inbreeding and genetic relatedness of individuals within populations and genetic differentiation among populations was characterized using AFLP markers. Populations were sampled in the Swiss Alps at 1800 (upper periphery of the study organisms) and at 1200 m a.s.l. Genetic diversity was not affected by altitude and only in B. media inbreeding was greater at higher altitudes. Genetic differentiation was slightly greater among populations at higher altitudes in B. media and individuals within populations were more related to each other compared to individuals in lower altitude populations. A similar but less strong pattern of differentiation and relatedness was observed in T. montanum, while in R. bulbosus there was no effect of altitude. Estimations of population size and isolation of populations were similar, both at higher and lower altitudes. Conclusions/Significance Our results suggest that altitude does not affect genetic diversity in the grassland species under study. Genetic differentiation of populations increased only slightly at higher elevation, probably due to extensive (historic) gene flow among altitudes. Potentially pre-adapted genes might therefore spread easily across altitudes. Our study indicates that populations at the upper periphery are not genetically depauperate or isolated and thus may be important source populations for migration under climate change. PMID:22870236

Analyte species and concentration identification using differentially functionalized microcantilever arrays and artificial neural networks

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

Senesac, Larry R; Datskos, Panos G; Sepaniak, Michael J

2006-01-01

In the present work, we have performed analyte species and concentration identification using an array of ten differentially functionalized microcantilevers coupled with a back-propagation artificial neural network pattern recognition algorithm. The array consists of ten nanostructured silicon microcantilevers functionalized by polymeric and gas chromatography phases and macrocyclic receptors as spatially dense, differentially responding sensing layers for identification and quantitation of individual analyte(s) and their binary mixtures. The array response (i.e. cantilever bending) to analyte vapor was measured by an optical readout scheme and the responses were recorded for a selection of individual analytes as well as several binary mixtures. Anmore » artificial neural network (ANN) was designed and trained to recognize not only the individual analytes and binary mixtures, but also to determine the concentration of individual components in a mixture. To the best of our knowledge, ANNs have not been applied to microcantilever array responses previously to determine concentrations of individual analytes. The trained ANN correctly identified the eleven test analyte(s) as individual components, most with probabilities greater than 97%, whereas it did not misidentify an unknown (untrained) analyte. Demonstrated unique aspects of this work include an ability to measure binary mixtures and provide both qualitative (identification) and quantitative (concentration) information with array-ANN-based sensor methodologies.« less

Closely related dermatophyte species produce different patterns of secreted proteins.

PubMed

Giddey, Karin; Favre, Bertrand; Quadroni, Manfredo; Monod, Michel

2007-02-01

Dermatophytes are the most common infectious agents responsible for superficial mycosis in humans and animals. Various species in this group of fungi show overlapping characteristics. We investigated the possibility that closely related dermatophyte species with different behaviours secrete distinct proteins when grown in the same culture medium. Protein patterns from culture filtrates of several strains of the same species were very similar. In contrast, secreted protein profiles from various species were different, and so a specific signature could be associated with each of the six analysed species. In particular, protein patterns were useful to distinguish Trichophyton tonsurans from Trichophyton equinum, which cannot be differentiated by ribosomal DNA sequencing. The secreted proteases Sub2, Sub6 and Sub7 of the subtilisin family, as well as Mep3 and Mep4 of the fungalisin family were identified. SUB6, SUB7, MEP3 and MEP4 genes were cloned and sequenced. Although the protein sequence of each protease was highly conserved across species, their level of secretion by the various species was not equivalent. These results suggest that a switch of habitat could be related to a differential expression of genes encoding homologous secreted proteins.

Shavenbaby Couples Patterning to Epidermal Cell Shape Control

PubMed Central

Fernandes, Isabelle; Roch, Fernando; Payre, François

2006-01-01

It is well established that developmental programs act during embryogenesis to determine animal morphogenesis. How these developmental cues produce specific cell shape during morphogenesis, however, has remained elusive. We addressed this question by studying the morphological differentiation of the Drosophila epidermis, governed by a well-known circuit of regulators leading to a stereotyped pattern of smooth cells and cells forming actin-rich extensions (trichomes). It was shown that the transcription factor Shavenbaby plays a pivotal role in the formation of trichomes and underlies all examined cases of the evolutionary diversification of their pattern. To gain insight into the mechanisms of morphological differentiation, we sought to identify shavenbaby's downstream targets. We show here that Shavenbaby controls epidermal cell shape, through the transcriptional activation of different classes of cellular effectors, directly contributing to the organization of actin filaments, regulation of the extracellular matrix, and modification of the cuticle. Individual inactivation of shavenbaby's targets produces distinct trichome defects and only their simultaneous inactivation prevent trichome formation. Our data show that shavenbaby governs an evolutionarily conserved developmental module consisting of a set of genes collectively responsible for trichome formation, shedding new light on molecular mechanisms acting during morphogenesis and the way they can influence evolution of animal forms. PMID:16933974

Nutrigenetics and nutrigenomics of caloric restriction.

PubMed

Abete, Itziar; Navas-Carretero, Santiago; Marti, Amelia; Martinez, J Alfredo

2012-01-01

Obesity is a complex disease resulting from a chronic and long-term positive energy balance in which both genetic and environmental factors are involved. Weight-reduction methods are mainly focused on dietary changes and increased physical activity. However, responses to nutritional intervention programs show a wide range of interindividual variation, which is importantly influenced by genetic determinants. In this sense, subjects carrying several obesity-related single-nucleotide polymorphisms (SNPs) show differences in the response to calorie-restriction programs. Furthermore, there is evidence indicating that dietary components not only fuel the body but also participate in the modulation of gene expression. Thus, the expression pattern and nutritional regulation of several obesity-related genes have been studied, as well as those that are differentially expressed by caloric restriction. The responses to caloric restriction linked to the presence of SNPs in obesity-related genes are reviewed in this chapter. Also, the influence of energy restriction on gene expression pattern in different tissues is addressed. Copyright © 2012 Elsevier Inc. All rights reserved.

Differentiation of Colletotrichum species responsible for anthracnose of strawberry by arbitrarily primed PCR

USGS Publications Warehouse

Freeman, S.; Rodriguez, R.J.

1995-01-01

A collection of 39 isolates of Colletotrichum acutatum, C. fragariae and C. gloeosporioides, which cause anthracnose on strawberry, was grouped into species based on the arbitrarily primed polymerase chain reaction (ap-PCR). All isolates used had previously been identified according to classical taxonomic morphology. Ap-PCR amplification of genomic DNA using four different primers allowed for reliable differentiation between isolates of C. acutatum, C. fragariae and two genotypes of C. gloeosporioides. Fifteen of the 18 C. acutatum isolates were very similar, although three isolates which produced a red pigment had distinctly different banding patterns. Nearly identical banding patterns were observed for all nine isolates of C. fragariae. The 12 C. gloeosporioides isolates were more diverse and two separate genotypes, Cgl-1 (six isolates) and Cgl-2 (five isolates) were distinguished by ap-PCR. An additional isolate did not conform to either the Cgl-1 or Cgl-2 genotypes. The utility of ap-PCR compared with other molecular techniques for reliable identification of Colletotrichum isolates pathogenic on strawberry is discussed.

Adipose tissue-derived stem cell response to the differently processed 316L stainless steel substrates.

PubMed

Faghihi, Shahab; Zia, Sonia; Taha, Masoumeh Fakhr

2012-12-01

Stainless steel (SS) is one of the most applicable materials in fabrication of cardiac implants. The aim of this study is to investigate the effect of atomic structure of polycrystalline stainless steel on the response of adipose tissue-derived stem cells (ADSCs). Samples are prepared from differently processed extruded rod and rolled sheet of 316L SS having different crystallographic structure. X-ray diffraction analysis indicated (200) and (111) orientations with distinct volume fractions in the specimens. Morphology and ADSCs behavior including adhesion, proliferation and differentiation are assessed. The expression of cardiac specific protein (cardiac troponin I) and genes of differentiating cardiomyocytes is analyzed by immunofluorescence and RT-PCR. The number of attached and grown cells on the rod sample is higher than the sheet sample also the scanning electron microscopy (SEM) analysis of ADSCs grown on the samples demonstrates higher cell density and spreading pattern on the surface of rod sample. In differentiated ADSCs on the rod sample the expression of all genes except ANF are detectable, while on the sheet sample only the MEF2C and β-MHC are expressed. This study shows that the cellular response is influenced by the crystal structure of the substrate therefore; the skill to alter the structure of substrate may lend itself to engineer a biomaterial which could be suitable for differentiation of stem cells into a definite lineage. Copyright © 2012 Elsevier Ltd. All rights reserved.

Auxin Influx Carriers Control Vascular Patterning and Xylem Differentiation in Arabidopsis thaliana

PubMed Central

Siligato, Riccardo; Alonso, Jose M.; Swarup, Ranjan; Bennett, Malcolm J.; Mähönen, Ari Pekka; Caño-Delgado, Ana I.; Ibañes, Marta

2015-01-01

Auxin is an essential hormone for plant growth and development. Auxin influx carriers AUX1/LAX transport auxin into the cell, while auxin efflux carriers PIN pump it out of the cell. It is well established that efflux carriers play an important role in the shoot vascular patterning, yet the contribution of influx carriers to the shoot vasculature remains unknown. Here, we combined theoretical and experimental approaches to decipher the role of auxin influx carriers in the patterning and differentiation of vascular tissues in the Arabidopsis inflorescence stem. Our theoretical analysis predicts that influx carriers facilitate periodic patterning and modulate the periodicity of auxin maxima. In agreement, we observed fewer and more spaced vascular bundles in quadruple mutants plants of the auxin influx carriers aux1lax1lax2lax3. Furthermore, we show AUX1/LAX carriers promote xylem differentiation in both the shoot and the root tissues. Influx carriers increase cytoplasmic auxin signaling, and thereby differentiation. In addition to this cytoplasmic role of auxin, our computational simulations propose a role for extracellular auxin as an inhibitor of xylem differentiation. Altogether, our study shows that auxin influx carriers AUX1/LAX regulate vascular patterning and differentiation in plants. PMID:25922946

Wound outcome in combat injuries is associated with a unique set of protein biomarkers

PubMed Central

2013-01-01

Background The ability to forecast whether a wound will heal after closure without further debridement(s), would provide substantial benefits to patients with severe extremity trauma. Methods Wound effluent is a readily available material which can be collected without disturbing healthy tissue. For analysis of potential host response biomarkers, forty four serial combat wound effluent samples from 19 patients with either healing or failing traumatic- and other combat-related wounds were examined by 2-D DIGE. Spot map patterns were correlated to eventual wound outcome (healed or wound failure) and analyzed using DeCyder 7.0 and differential proteins identified via LC-MS/MS. Results This approach identified 52 protein spots that were differentially expressed and thus represent candidate biomarkers for this clinical application. Many of these proteins are intimately involved in inflammatory and immune responses. Furthermore, discriminate analysis further refined the 52 differential protein spots to a smaller subset of which successfully differentiate between wounds that will heal and those that will fail and require further surgical intervention with greater than 83% accuracy. Conclusion These results suggest candidates for a panel of protein biomarkers that may aid traumatic wound care prognosis and treatment. We recommend that this strategy be refined, and then externally validated, in future studies of traumatic wounds. PMID:24192341

Differential gene expression profiles of peripheral blood mononuclear cells in childhood asthma.

PubMed

Kong, Qian; Li, Wen-Jing; Huang, Hua-Rong; Zhong, Ying-Qiang; Fang, Jian-Pei

2015-05-01

Asthma is a common childhood disease with strong genetic components. This study compared whole-genome expression differences between asthmatic young children and healthy controls to identify gene signatures of childhood asthma. Total RNA extracted from peripheral blood mononuclear cells (PBMC) was subjected to microarray analysis. QRT-PCR was performed to verify the microarray results. Classification and functional characterization of differential genes were illustrated by hierarchical clustering and gene ontology analysis. Multiple logistic regression (MLR) analysis, receiver operating characteristic (ROC) curve analysis, and discriminate power were used to scan asthma-specific diagnostic markers. For fold-change>2 and p < 0.05, there were 758 named differential genes. The results of QRT-PCR confirmed successfully the array data. Hierarchical clustering divided 29 highly possible genes into seven categories and the genes in the same cluster were likely to possess similar expression patterns or functions. Gene ontology analysis presented that differential genes primarily enriched in immune response, response to stress or stimulus, and regulation of apoptosis in biological process. MLR and ROC curve analysis revealed that the combination of ADAM33, Smad7, and LIGHT possessed excellent discriminating power. The combination of ADAM33, Smad7, and LIGHT would be a reliable and useful childhood asthma model for prediction and diagnosis.

Evidences of local adaptation in quantitative traits in Prosopis alba (Leguminosae).

PubMed

Bessega, C; Pometti, C; Ewens, M; Saidman, B O; Vilardi, J C

2015-02-01

Signals of selection on quantitative traits can be detected by the comparison between the genetic differentiation of molecular (neutral) markers and quantitative traits, by multivariate extensions of the same model and by the observation of the additive covariance among relatives. We studied, by three different tests, signals of occurrence of selection in Prosopis alba populations over 15 quantitative traits: three economically important life history traits: height, basal diameter and biomass, 11 leaf morphology traits that may be related with heat-tolerance and physiological responses and spine length that is very important from silvicultural purposes. We analyzed 172 G1-generation trees growing in a common garden belonging to 32 open pollinated families from eight sampling sites in Argentina. The multivariate phenotypes differ significantly among origins, and the highest differentiation corresponded to foliar traits. Molecular genetic markers (SSR) exhibited significant differentiation and allowed us to provide convincing evidence that natural selection is responsible for the patterns of morphological differentiation. The heterogeneous selection over phenotypic traits observed suggested different optima in each population and has important implications for gene resource management. The results suggest that the adaptive significance of traits should be considered together with population provenance in breeding program as a crucial point prior to any selecting program, especially in Prosopis where the first steps are under development.

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

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

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

2014-08-01

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

Metacarpophalangeal pattern profile analysis: useful diagnostic tool for differentiating between dyschondrosteosis, Turner syndrome, and hypochondroplasia.

PubMed

Laurencikas, E; Sävendahl, L; Jorulf, H

2006-06-01

To assess the value of the metacarpophalangeal pattern profile (MCPP) analysis as a diagnostic tool for differentiating between patients with dyschondrosteosis, Turner syndrome, and hypochondroplasia. Radiographic and clinical data from 135 patients between 1 and 51 years of age were collected and analyzed. The study included 25 patients with hypochondroplasia (HCP), 39 with dyschondrosteosis (LWD), and 71 with Turner syndrome (TS). Hand pattern profiles were calculated and compared with those of 110 normal individuals. Pearson correlation coefficient (r) and multivariate discriminant analysis were used for pattern profile analysis. Pattern variability index, a measure of dysmorphogenesis, was calculated for LWD, TS, HCP, and normal controls. Our results demonstrate that patients with LWD, TS, or HCP have distinct pattern profiles that are significantly different from each other and from those of normal controls. Discriminant analysis yielded correct classification of normal versus abnormal individuals in 84% of cases. Classification of the patients into LWD, TS, and HCP groups was successful in 75%. The correct classification rate was higher (85%) when differentiating two pathological groups at a time. Pattern variability index was not helpful for differential diagnosis of LWD, TS, and HCP. Patients with LWD, TS, or HCP have distinct MCPPs and can be successfully differentiated from each other using advanced MCPP analysis. Discriminant analysis is to be preferred over Pearson correlation coefficient because it is a more sensitive and specific technique. MCPP analysis is a helpful tool for differentiating between syndromes with similar clinical and radiological abnormalities.

Identification of Crowding Stress Tolerance Co-Expression Networks Involved in Sweet Corn Yield

PubMed Central

Choe, Eunsoo; Drnevich, Jenny; Williams, Martin M.

2016-01-01

Tolerance to crowding stress has played a crucial role in improving agronomic productivity in field corn; however, commercial sweet corn hybrids vary greatly in crowding stress tolerance. The objectives were to 1) explore transcriptional changes among sweet corn hybrids with differential yield under crowding stress, 2) identify relationships between phenotypic responses and gene expression patterns, and 3) identify groups of genes associated with yield and crowding stress tolerance. Under conditions of crowding stress, three high-yielding and three low-yielding sweet corn hybrids were grouped for transcriptional and phenotypic analyses. Transcriptional analyses identified from 372 to 859 common differentially expressed genes (DEGs) for each hybrid. Large gene expression pattern variation among hybrids and only 26 common DEGs across all hybrid comparisons were identified, suggesting each hybrid has a unique response to crowding stress. Over-represented biological functions of DEGs also differed among hybrids. Strong correlation was observed between: 1) modules with up-regulation in high-yielding hybrids and yield traits, and 2) modules with up-regulation in low-yielding hybrids and plant/ear traits. Modules linked with yield traits may be important crowding stress response mechanisms influencing crop yield. Functional analysis of the modules and common DEGs identified candidate crowding stress tolerant processes in photosynthesis, glycolysis, cell wall, carbohydrate/nitrogen metabolic process, chromatin, and transcription regulation. Moreover, these biological functions were greatly inter-connected, indicating the importance of improving the mechanisms as a network. PMID:26796516

Oral candidosis in relation to oral immunity.

PubMed

Feller, L; Khammissa, R A G; Chandran, R; Altini, M; Lemmer, J

2014-09-01

Symptomatic oral infection with Candida albicans is characterized by invasion of the oral epithelium by virulent hyphae that cause tissue damage releasing the inflammatory mediators that initiate and sustain local inflammation. Candida albicans triggers pattern-recognition receptors of keratinocytes, macrophages, monocytes and dendritic cells, stimulating the production of IL-1β, IL-6 and IL-23. These cytokines induce the differentiation of Th17 cells and the generation of IL-17- and/or IL-22-mediated antifungal protective immuno-inflammatory responses in infected mucosa. Some immune cells including NKT cells, γδ T cells and lymphoid cells that are innate to the oral mucosa have the capacity to produce large quantities of IL-17 in response to C. albicans, sufficient to mediate effective protective immunity against C. albicans. On the other hand, molecular structures of commensal C. albicans blastoconidia, although detected by pattern-recognition receptors, are avirulent, do not invade the oral epithelium, do not elicit inflammatory responses in a healthy host, but induce regulatory immune responses that maintain tissue tolerance to the commensal fungi. The type, specificity and sensitivity of the protective immune response towards C. albicans is determined by the outcome of the integrated interactions between the intracellular signalling pathways of specific combinations of activated pattern-recognition receptors (TLR2, TLR4, Dectin-1 and Dectin-2). IL-17-mediated protective immune response is essential for oral mucosal immunity to C. albicans infection. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification of genes differentially expressed during interaction of resistant and susceptible apple cultivars (Malus × domestica) with Erwinia amylovora

PubMed Central

2010-01-01

Background The necrogenic enterobacterium, Erwinia amylovora is the causal agent of the fire blight (FB) disease in many Rosaceaespecies, including apple and pear. During the infection process, the bacteria induce an oxidative stress response with kinetics similar to those induced in an incompatible bacteria-plant interaction. No resistance mechanism to E. amylovora in host plants has yet been characterized, recent work has identified some molecular events which occur in resistant and/or susceptible host interaction with E. amylovora: In order to understand the mechanisms that characterize responses to FB, differentially expressed genes were identified by cDNA-AFLP analysis in resistant and susceptible apple genotypes after inoculation with E. amylovora. Results cDNA were isolated from M.26 (susceptible) and G.41 (resistant) apple tissues collected 2 h and 48 h after challenge with a virulent E. amylovora strain or mock (buffer) inoculated. To identify differentially expressed transcripts, electrophoretic banding patterns were obtained from cDNAs. In the AFLP experiments, M.26 and G.41 showed different patterns of expression, including genes specifically induced, not induced, or repressed by E. amylovora. In total, 190 ESTs differentially expressed between M.26 and G.41 were identified using 42 pairs of AFLP primers. cDNA-AFLP analysis of global EST expression in a resistant and a susceptible apple genotype identified different major classes of genes. EST sequencing data showed that genes linked to resistance, encoding proteins involved in recognition, signaling, defense and apoptosis, were modulated by E. amylovora in its host plant. The expression time course of some of these ESTs selected via a bioinformatic analysis has been characterized. Conclusion These data are being used to develop hypotheses of resistance or susceptibility mechanisms in Malus to E. amylovora and provide an initial categorization of genes possibly involved in recognition events, early signaling responses the subsequent development of resistance or susceptibility. These data also provided potential candidates for improving apple resistance to fire blight either by marker-assisted selection or genetic engineering. PMID:20047654

Acute fibrinous and organising pneumonia.

PubMed

Guimarães, Catarina; Sanches, Inês; Ferreira, Catarina

2012-03-20

Acute fibrinous and organising pneumonia (AFOP) was recently described as an unusual pattern of diffuse lung disease. Particular characteristics make the differential diagnosis with the well recognised clinical patterns of diffuse alveolar damage, cryptogenic organising pneumonia or eosinophilic pneumonia. The lack of hyaline membranes, the presence of intra-alveolar fibrin, absence of noticeable eosinophils and patchy distribution suggests that AFOP define a distinct histological pattern. The authors describe the case of a woman diagnosed with AFOP after surgical lung biopsy, in association with primary biliary cirrhosis. The patient presented dyspnoea, fatigue, dry cough and thoracic pain. The CT scan showed bilateral patchy infiltrates predominantly in the lower lobes. Flexible bronchoscopy and subsidiary techniques were inconclusive and biopsy through video-assisted thoracoscopic surgery led to anatomopathological diagnosis of AFOP. The patient is having a good clinical response to prednisone.

Feedback-driven response to multidecadal climatic variability at an alpine treeline

USGS Publications Warehouse

Alftine, K.J.; Malanson, G.P.; Fagre, D.B.

2003-01-01

The Pacific Decadal Oscillation (PDO) has significant climatological and ecological effects in northwestern North America. Its possible effects and their modification by feedbacks are examined in the forest-tundra ecotone in Glacier National Park, Montana, USA. Tree ring samples were collected to estimate establishment dates in 10 quadrats. Age-diameter regressions were used to estimate the ages of uncored trees. The temporal pattern of establishment and survival was compared to the pattern of the PDO. A wave of establishment began in the mid-1940s, rose to a peak rate in the mid-1970s, and dropped precipitously beginning ca. 1980 to near zero for the 1990s. The period of establishment primarily coincided with the negative phase of the PDO, but the establishment and survival pattern is not correlated with the PDO index. The pattern indicates a period during which establishment was possible and was augmented by positive feedback from surviving trees. Snow may be the most important factor in the feedback, but studies indicate that its effects vary locally. Spatially differentiated analyses of decadal or longer periodicity may elucidate responses to climatic variation. ?? 2003 by V. H. Winston and Son, Inc. All rights reserved.

A photoreversible protein-patterning approach for guiding stem cell fate in three-dimensional gels

NASA Astrophysics Data System (ADS)

Deforest, Cole A.; Tirrell, David A.

2015-05-01

Although biochemically patterned hydrogels are capable of recapitulating many critical aspects of the heterogeneous cellular niche, exercising spatial and temporal control of the presentation and removal of biomolecular signalling cues in such systems has proved difficult. Here, we demonstrate a synthetic strategy that exploits two bioorthogonal photochemistries to achieve reversible immobilization of bioactive full-length proteins with good spatial and temporal control within synthetic, cell-laden biomimetic scaffolds. A photodeprotection-oxime-ligation sequence permits user-defined quantities of proteins to be anchored within distinct subvolumes of a three-dimensional matrix, and an ortho-nitrobenzyl ester photoscission reaction facilitates subsequent protein removal. By using this approach to pattern the presentation of the extracellular matrix protein vitronectin, we accomplished reversible differentiation of human mesenchymal stem cells to osteoblasts in a spatially defined manner. Our protein-patterning approach should provide further avenues to probe and direct changes in cell physiology in response to dynamic biochemical signalling.

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

PubMed Central

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

2011-01-01

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

The Intersection of the Extrinsic Hedgehog and WNT/Wingless Signals with the Intrinsic Hox Code Underpins Branching Pattern and Tube Shape Diversity in the Drosophila Airways

PubMed Central

Matsuda, Ryo; Hosono, Chie; Saigo, Kaoru; Samakovlis, Christos

2015-01-01

The tubular networks of the Drosophila respiratory system and our vasculature show distinct branching patterns and tube shapes in different body regions. These local variations are crucial for organ function and organismal fitness. Organotypic patterns and tube geometries in branched networks are typically controlled by variations of extrinsic signaling but the impact of intrinsic factors on branch patterns and shapes is not well explored. Here, we show that the intersection of extrinsic hedgehog(hh) and WNT/wingless (wg) signaling with the tube-intrinsic Hox code of distinct segments specifies the tube pattern and shape of the Drosophila airways. In the cephalic part of the airways, hh signaling induces expression of the transcription factor (TF) knirps (kni) in the anterior dorsal trunk (DTa1). kni represses the expression of another TF spalt major (salm), making DTa1 a narrow and long tube. In DTa branches of more posterior metameres, Bithorax Complex (BX-C) Hox genes autonomously divert hh signaling from inducing kni, thereby allowing DTa branches to develop as salm-dependent thick and short tubes. Moreover, the differential expression of BX-C genes is partly responsible for the anterior-to-posterior gradual increase of the DT tube diameter through regulating the expression level of Salm, a transcriptional target of WNT/wg signaling. Thus, our results highlight how tube intrinsic differential competence can diversify tube morphology without changing availabilities of extrinsic factors. PMID:25615601

Functional link between DNA damage responses and transcriptional regulation by ATM in response to a histone deacetylase inhibitor TSA.

PubMed

Lee, Jong-Soo

2007-09-01

Mutations in the ATM (ataxia-telangiectasia mutated) gene, which encodes a 370 kd protein with a kinase catalytic domain, predisposes people to cancers, and these mutations are also linked to ataxia-telangiectasia (A-T). The histone acetylaion/deacetylation- dependent chromatin remodeling can activate the ATM kinase-mediated DNA damage signal pathway (in an accompanying work, Lee, 2007). This has led us to study whether this modification can impinge on the ATM-mediated DNA damage response via transcriptional modulation in order to understand the function of ATM in the regulation of gene transcription. To identify the genes whose expression is regulated by ATM in response to histone deaceylase (HDAC) inhibition, we performed an analysis of oligonucleotide microarrays with using the appropriate cell lines, isogenic A-T (ATM(-)) and control (ATM(+)) cells, following treatment with a HDAC inhibitor TSA. Treatment with TSA reprograms the differential gene expression profile in response to HDAC inhibition in ATM(-) cells and ATM(+) cells. We analyzed the genes that are regulated by TSA in the ATM-dependent manner, and we classified these genes into different functional categories, including those involved in cell cycle/DNA replication, DNA repair, apoptosis, growth/differentiation, cell- cell adhesion, signal transduction, metabolism and transcription. We found that while some genes are regulated by TSA without regard to ATM, the patterns of gene regulation are differentially regulated in an ATM-dependent manner. Taken together, these finding indicate that ATM can regulate the transcription of genes that play critical roles in the molecular response to DNA damage, and this response is modulated through an altered HDAC inhibition-mediated gene expression.

Protein nanoparticles are nontoxic, tuneable cell stressors.

PubMed

de Pinho Favaro, Marianna Teixeira; Sánchez-García, Laura; Sánchez-Chardi, Alejandro; Roldán, Mónica; Unzueta, Ugutz; Serna, Naroa; Cano-Garrido, Olivia; Azzoni, Adriano Rodrigues; Ferrer-Miralles, Neus; Villaverde, Antonio; Vázquez, Esther

2018-02-01

Nanoparticle-cell interactions can promote cell toxicity and stimulate particular behavioral patterns, but cell responses to protein nanomaterials have been poorly studied. By repositioning oligomerization domains in a simple, modular self-assembling protein platform, we have generated closely related but distinguishable homomeric nanoparticles. Composed by building blocks with modular domains arranged in different order, they share amino acid composition. These materials, once exposed to cultured cells, are differentially internalized in absence of toxicity and trigger distinctive cell adaptive responses, monitored by the emission of tubular filopodia and enhanced drug sensitivity. The capability to rapidly modulate such cell responses by conventional protein engineering reveals protein nanoparticles as tuneable, versatile and potent cell stressors for cell-targeted conditioning.

CD8 single-cell gene coexpression reveals three different effector types present at distinct phases of the immune response

PubMed Central

Peixoto, António; Evaristo, César; Munitic, Ivana; Monteiro, Marta; Charbit, Alain; Rocha, Benedita; Veiga-Fernandes, Henrique

2007-01-01

To study in vivo CD8 T cell differentiation, we quantified the coexpression of multiple genes in single cells throughout immune responses. After in vitro activation, CD8 T cells rapidly express effector molecules and cease their expression when the antigen is removed. Gene behavior after in vivo activation, in contrast, was quite heterogeneous. Different mRNAs were induced at very different time points of the response, were transcribed during different time periods, and could decline or persist independently of the antigen load. Consequently, distinct gene coexpression patterns/different cell types were generated at the various phases of the immune responses. During primary stimulation, inflammatory molecules were induced and down-regulated shortly after activation, generating early cells that only mediated inflammation. Cytotoxic T cells were generated at the peak of the primary response, when individual cells simultaneously expressed multiple killer molecules, whereas memory cells lost killer capacity because they no longer coexpressed killer genes. Surprisingly, during secondary responses gene transcription became permanent. Secondary cells recovered after antigen elimination were more efficient killers than cytotoxic T cells present at the peak of the primary response. Thus, primary responses produced two transient effector types. However, after boosting, CD8 T cells differentiate into long-lived killer cells that persist in vivo in the absence of antigen. PMID:17485515

Investigation of protein expression profiles of erythritol-producing Candida magnoliae in response to glucose perturbation.

PubMed

Kim, Hyo Jin; Lee, Hyeong-Rho; Kim, Chang Sup; Jin, Yong-Su; Seo, Jin-Ho

2013-08-15

Protein expression patterns of an erythritol-producing yeast, Candida magnoliae, were analyzed to identify differentially expressed proteins in response to glucose perturbation. Specifically, wild type C. magnoliae was grown under high and low glucose conditions and the cells were harvested at both mid-exponential and erythritol production phases for proteomic studies. In order to analyze intracellular protein abundances from the harvested cells quantitatively, total intracellular proteins were extracted and applied to two-dimensional gel electrophoresis for separation and visualization of individual proteins. Among the proteins distributed in the range of pI 4-7 and molecular weight 29-97kDa, five osmo-responsive proteins were drastically changed in response to glucose perturbation. Hsp60 (Heat-shock protein 60), transaldolase and NADH:quinone oxidoreductase were down-regulated under the high glucose condition and Bro1 (BCK1-like Resistance to Osmotic shock) and Eno1 (enolase1) were up-regulated. These proteins are directly or indirectly related with cellular stress response. Importantly, protein expression patterns of Hsp60, Bro1 and Eno1 were strongly correlated with previous studies identifying the proteins perturbed by osmotic stress for other organisms including Saccharomyces cerevisiae. Copyright © 2013 Elsevier Inc. All rights reserved.

Explicit and Implicit Second Language Training Differentially Affect the Achievement of Native-like Brain Activation Patterns

PubMed Central

Morgan-Short, Kara; Steinhauer, Karsten; Sanz, Cristina; Ullman, Michael T.

2013-01-01

It is widely believed that adults cannot learn a foreign language in the same way that children learn a first language. However, recent evidence suggests that adult learners of a foreign language can come to rely on native-like language brain mechanisms. Here, we show that the type of language training crucially impacts this outcome. We used an artificial language paradigm to examine longitudinally whether explicit training (that approximates traditional grammar-focused classroom settings) and implicit training (that approximates immersion settings) differentially affect neural (electrophysiological) and behavioral (performance) measures of syntactic processing. Results showed that performance of explicitly and implicitly trained groups did not differ at either low or high proficiency. In contrast, electrophysiological (ERP) measures revealed striking differences between the groups’ neural activity at both proficiency levels in response to syntactic violations. Implicit training yielded an N400 at low proficiency, whereas at high proficiency, it elicited a pattern typical of native speakers: an anterior negativity followed by a P600 accompanied by a late anterior negativity. Explicit training, by contrast, yielded no significant effects at low proficiency and only an anterior positivity followed by a P600 at high proficiency. Although the P600 is reminiscent of native-like processing, this response pattern as a whole is not. Thus, only implicit training led to an electrophysiological signature typical of native speakers. Overall, the results suggest that adult foreign language learners can come to rely on native-like language brain mechanisms, but that the conditions under which the language is learned may be crucial in attaining this goal. PMID:21861686

Design a New Strategy Based on Nanoparticle-Enhanced Chemiluminescence Sensor Array for Biothiols Discrimination

NASA Astrophysics Data System (ADS)

Shahrajabian, Maryam; Hormozi-Nezhad, M. Reza

2016-08-01

Array-based sensor is an interesting approach that suggests an alternative to expensive analytical methods. In this work, we introduce a novel, simple, and sensitive nanoparticle-based chemiluminescence (CL) sensor array for discrimination of biothiols (e.g., cysteine, glutathione and glutathione disulfide). The proposed CL sensor array is based on the CL efficiencies of four types of enhanced nanoparticle-based CL systems. The intensity of CL was altered to varying degrees upon interaction with biothiols, producing unique CL response patterns. These distinct CL response patterns were collected as “fingerprints” and were then identified through chemometric methods, including linear discriminant analysis (LDA) and hierarchical cluster analysis (HCA). The developed array was able to successfully differentiate between cysteine, glutathione and glutathione disulfide in a wide concentration range. Moreover, it was applied to distinguish among the above analytes in human plasma.

Field-deployable sniffer for 2,4-dinitrotoluene detection.

PubMed

Albert, K J; Myrick, M L; Brown, S B; James, D L; Milanovich, F P; Walt, D R

2001-08-01

A field-deployable instrument has been developed to detect low-level 2,4-dinitrotoluene (2,4-DNT) vapors. The system is based on previously developed artificial nose technology and employs an array of sensory materials attached to the distal tips of an optical fiber bundle. Both semiselective and nonspecific, cross-reactive sensors were employed. Each sensor within the array responds differentially to vapor exposure so the array's fluorescence response patterns are unique for each analyte. The instrument is computationally "trained" to discriminate target response patterns from nontarget and background environments. This detection system has been applied to detect 2,4-DNT, an analyte commonly detected on the soil surface above buried 2,4,6-trinitrotoluene (TNT) land mines, in spiked soil and aqueous and ground samples. The system has been characterized and demonstrated the ability to detect 120 ppb 2,4-DNT vapor in blind (unknown) humidified samples during a supervised field test.

Microscale architecture in biomaterial scaffolds for spatial control of neural cell behavior

NASA Astrophysics Data System (ADS)

Meco, Edi; Lampe, Kyle J.

2018-02-01

Biomaterial scaffolds mimic aspects of the native central nervous system (CNS) extracellular matrix (ECM) and have been extensively utilized to influence neural cell (NC) behavior in in vitro and in vivo settings. These biomimetic scaffolds support NC cultures, can direct the differentiation of NCs, and have recapitulated some native NC behavior in an in vitro setting. However, NC transplant therapies and treatments used in animal models of CNS disease and injury have not fully restored functionality. The observed lack of functional recovery occurs despite improvements in transplanted NC viability when incorporating biomaterial scaffolds and the potential of NC to replace damaged native cells. The behavior of NCs within biomaterial scaffolds must be directed in order to improve the efficacy of transplant therapies and treatments. Biomaterial scaffold topography and imbedded bioactive cues, designed at the microscale level, can alter NC phenotype, direct migration, and differentiation. Microscale patterning in biomaterial scaffolds for spatial control of NC behavior has enhanced the capabilities of in vitro models to capture properties of the native CNS tissue ECM. Patterning techniques such as lithography, electrospinning and 3D bioprinting can be employed to design the microscale architecture of biomaterial scaffolds. Here, the progress and challenges of the prevalent biomaterial patterning techniques of lithography, electrospinning, and 3D bioprinting are reported. This review analyzes NC behavioral response to specific microscale topographical patterns and spatially organized bioactive cues.

Effects of irradiation on stem cell response to differentiation inhibitors in the Planarian Dugesia etrusca

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

Steele, V.E.; Lange, C.S.

1976-07-01

The planarian owes its extensive powers of regeneration to the possession of a totipotential stem cell system. The survival of the animal after irradiation depends mainly upon this system. In this respect the planarian is analogous to mammalian organ systems such as bone marrow or gut epithelium. The differentiated cells control the course of stem cell mediated tissue renewal by the secretion of differentiator and/or inhibitor substances. One such inhibitor substance, present in extracts prepared from homogenized whole planarians, specifically inhibits brain formation. This substance is organ specific, but not species specific. The differentiative integrity of the stem cells aftermore » irradiation is measured by comparing the regenerated brain volumes resulting from the presence or absence of the brain inhibitory extract during the regeneration period. Our data suggest that increasing doses of x irradiation decreases the ability of the stem cells to respond to differentiative substances. The data presented also explore the possibility of altering the postirradiation recovery pattern by shifting the differentiative demands placed on the stem cells. The final proportions of animals (one-half regenerated with, and one-half without, the extract) surviving after 60 days were not significantly different.« less

Antagonism between the transcription factors NANOG and OTX2 specifies rostral or caudal cell fate during neural patterning transition.

PubMed

Su, Zhenghui; Zhang, Yanqi; Liao, Baojian; Zhong, Xiaofen; Chen, Xin; Wang, Haitao; Guo, Yiping; Shan, Yongli; Wang, Lihui; Pan, Guangjin

2018-03-23

During neurogenesis, neural patterning is a critical step during which neural progenitor cells differentiate into neurons with distinct functions. However, the molecular determinants that regulate neural patterning remain poorly understood. Here we optimized the "dual SMAD inhibition" method to specifically promote differentiation of human pluripotent stem cells (hPSCs) into forebrain and hindbrain neural progenitor cells along the rostral-caudal axis. We report that neural patterning determination occurs at the very early stage in this differentiation. Undifferentiated hPSCs expressed basal levels of the transcription factor orthodenticle homeobox 2 (OTX2) that dominantly drove hPSCs into the "default" rostral fate at the beginning of differentiation. Inhibition of glycogen synthase kinase 3β (GSK3β) through CHIR99021 application sustained transient expression of the transcription factor NANOG at early differentiation stages through Wnt signaling. Wnt signaling and NANOG antagonized OTX2 and, in the later stages of differentiation, switched the default rostral cell fate to the caudal one. Our findings have uncovered a mutual antagonism between NANOG and OTX2 underlying cell fate decisions during neural patterning, critical for the regulation of early neural development in humans. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Development of an abbreviated Career Indecision Profile-65 using item response theory: The CIP-Short.

PubMed

Xu, Hui; Tracey, Terence J G

2017-03-01

The current study developed an abbreviated version of the Career Indecision Profile-65 (CIP-65; Hacker, Carr, Abrams, & Brown, 2013) by using item response theory. In order to improve the efficiency of the CIP-65 in measuring career indecision, the individual item performance of the CIP-65 was examined with respect to the ordering of response occurrence and gender differential item functioning. The best 5 items of each scale of the CIP-65 (i.e., neuroticism/negative affectivity, choice/commitment anxiety, lack of readiness, and interpersonal conflicts) were retained in the CIP-Short using a sample of 588 college students. A validation sample (N = 174) supported the reliability and structural validity of the CIP-Short. The convergent and divergent validity of the CIP-Short was additionally supported in the findings of a hypothesized differential relational pattern in a separate sample (N = 360). While the current study supported the CIP-Short being a sound brief measure of career indecision, the limitations of this study and suggestions for future research were discussed as well. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Grb2 regulates B-cell maturation, B-cell memory responses and inhibits B-cell Ca2+ signalling.

PubMed

Ackermann, Jochen A; Radtke, Daniel; Maurberger, Anna; Winkler, Thomas H; Nitschke, Lars

2011-04-20

Grb2 is a ubiquitously expressed adaptor protein, which activates Ras and MAP kinases in growth factor receptor signalling, while in B-cell receptor (BCR) signalling this role is controversial. In B cell lines it was shown that Grb2 can inhibit BCR-induced Ca(2+) signalling. Nonetheless, the physiological role of Grb2 in primary B cells is still unknown. We generated a B-cell-specific Grb2-deficient mouse line, which had a severe reduction of mature follicular B cells in the periphery due to a differentiation block and decreased B-cell survival. Moreover, we found several changes in important signalling pathways: enhanced BCR-induced Ca(2+) signalling, alterations in mitogen-activated protein kinase activation patterns and strongly impaired Akt activation, the latter pointing towards a defect in PI3K signalling. Interestingly, B-cell-specific Grb2-deficient mice showed impaired IgG and B-cell memory responses, and impaired germinal centre formation. Thus, Grb2-dependent signalling pathways are crucial for lymphocyte differentiation processes, as well as for control of secondary humoral immune responses.

Estradiol and progesterone influence on influenza infection and immune response in a mouse model.

PubMed

Davis, Sarah M; Sweet, Leigh M; Oppenheimer, Karen H; Suratt, Benjamin T; Phillippe, Mark

2017-10-01

Influenza infection severity may be mediated by estradiol and/or progesterone. An exploratory study was designed to evaluate 17-β-estradiol and progesterone on influenza infection and examine immune-mediated response in a mouse model. Inoculation with placebo or mouse-adapted H1N1 influenza virus occurred. Treatment groups included 17-β-estradiol, progesterone, ovariectomy, and pregnancy. Mice were assessed for morbidity and mortality. Toll-like receptor gene studies and airspace cell differentials were performed. Onset of morbidity was earlier and morbidity duration greater for progesterone. Absence of morbidity/mortality and overall survival was greater for 17-β-estradiol. Airspace cell differentials suggest improved immune cell recruitment for 17-β-estradiol. Pregnant mouse data demonstrate significant mortality during the period of increased progesterone. Select immune cell markers demonstrate patterns of regulation that may promote proper immune response to influenza infection for 17-β-estradiol. Estradiol may play a protective and progesterone a detrimental role in the pathophysiology of influenza infection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Quantitative deviating effects of maple syrup extract supplementation on the hepatic gene expression of mice fed a high-fat diet.

PubMed

Kamei, Asuka; Watanabe, Yuki; Shinozaki, Fumika; Yasuoka, Akihito; Shimada, Kousuke; Kondo, Kaori; Ishijima, Tomoko; Toyoda, Tsudoi; Arai, Soichi; Kondo, Takashi; Abe, Keiko

2017-02-01

Maple syrup contains various polyphenols and we investigated the effects of a polyphenol-rich maple syrup extract (MSXH) on the physiology of mice fed a high-fat diet (HFD). The mice fed a low-fat diet (LFD), an HFD, or an HFD supplemented with 0.02% (002MSXH) or 0.05% MSXH (005MSXH) for 4 weeks. Global gene expression analysis of the liver was performed, and the differentially expressed genes were classified into three expression patterns; pattern A (LFD < HFD > 002MSXH = 005MSXH, LFD > HFD < 002MSXH = 005MSXH), pattern B (LFD < HFD = 002MSXH > 005MSXH, LFD > HFD = 002MSXH < 005MSXH), and pattern C (LFD < HFD > 002MSXH < 005MSXH, LFD > HFD < 002MSXH > 005MSXH). Pattern A was enriched in glycolysis, fatty acid metabolism, and folate metabolism. Pattern B was enriched in tricarboxylic acid cycle while pattern C was enriched in gluconeogenesis, cholesterol metabolism, amino acid metabolism, and endoplasmic reticulum stress-related event. Our study suggested that the effects of MSXH ingestion showed (i) dose-dependent pattern involved in energy metabolisms and (ii) reversely pattern involved in stress responses. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A randomized trial of mailed questionnaires versus telephone interviews: Response patterns in a survey

PubMed Central

Feveile, Helene; Olsen, Ole; Hogh, Annie

2007-01-01

Background Data for health surveys are often collected using either mailed questionnaires, telephone interviews or a combination. Mode of data collection can affect the propensity to refuse to respond and result in different patterns of responses. The objective of this paper is to examine and quantify effects of mode of data collection in health surveys. Methods A stratified sample of 4,000 adults residing in Denmark was randomised to mailed questionnaires or computer-assisted telephone interviews. 45 health-related items were analyzed; four concerning behaviour and 41 concerning self assessment. Odds ratios for more positive answers and more frequent use of extreme response categories (both positive and negative) among telephone respondents compared to questionnaire respondents were estimated. Tests were Bonferroni corrected. Results For the four health behaviour items there were no significant differences in the response patterns. For 32 of the 41 health self assessment items the response pattern was statistically significantly different and extreme response categories were used more frequently among telephone respondents (Median estimated odds ratio: 1.67). For a majority of these mode sensitive items (26/32), a more positive reporting was observed among telephone respondents (Median estimated odds ratio: 1.73). The overall response rate was similar among persons randomly assigned to questionnaires (58.1%) and to telephone interviews (56.2%). A differential nonresponse bias for age and gender was observed. The rate of missing responses was higher for questionnaires (0.73 – 6.00%) than for telephone interviews (0 – 0.51%). The "don't know" option was used more often by mail respondents (10 – 24%) than by telephone respondents (2 – 4%). Conclusion The mode of data collection affects the reporting of self assessed health items substantially. In epidemiological studies, the method effect may be as large as the effects under investigation. Caution is needed when comparing prevalences across surveys or when studying time trends. PMID:17592653

Do people with and without medical conditions respond similarly to the short health anxiety inventory? An assessment of differential item functioning using item response theory.

PubMed

LeBouthillier, Daniel M; Thibodeau, Michel A; Alberts, Nicole M; Hadjistavropoulos, Heather D; Asmundson, Gordon J G

2015-04-01

Individuals with medical conditions are likely to have elevated health anxiety; however, research has not demonstrated how medical status impacts response patterns on health anxiety measures. Measurement bias can undermine the validity of a questionnaire by overestimating or underestimating scores in groups of individuals. We investigated whether the Short Health Anxiety Inventory (SHAI), a widely-used measure of health anxiety, exhibits medical condition-based bias on item and subscale levels, and whether the SHAI subscales adequately assess the health anxiety continuum. Data were from 963 individuals with diabetes, breast cancer, or multiple sclerosis, and 372 healthy individuals. Mantel-Haenszel tests and item characteristic curves were used to classify the severity of item-level differential item functioning in all three medical groups compared to the healthy group. Test characteristic curves were used to assess scale-level differential item functioning and whether the SHAI subscales adequately assess the health anxiety continuum. Nine out of 14 items exhibited differential item functioning. Two items exhibited differential item functioning in all medical groups compared to the healthy group. In both Thought Intrusion and Fear of Illness subscales, differential item functioning was associated with mildly deflated scores in medical groups with very high levels of the latent traits. Fear of Illness items poorly discriminated between individuals with low and very low levels of the latent trait. While individuals with medical conditions may respond differentially to some items, clinicians and researchers can confidently use the SHAI with a variety of medical populations without concern of significant bias. Copyright © 2015 Elsevier Inc. All rights reserved.

Differentiating Electromechanical From Non-Electrical Substrates of Mechanical Discoordination to Identify Responders to Cardiac Resynchronization Therapy.

PubMed

Lumens, Joost; Tayal, Bhupendar; Walmsley, John; Delgado-Montero, Antonia; Huntjens, Peter R; Schwartzman, David; Althouse, Andrew D; Delhaas, Tammo; Prinzen, Frits W; Gorcsan, John

2015-09-01

Left ventricular (LV) mechanical discoordination, often referred to as dyssynchrony, is often observed in patients with heart failure regardless of QRS duration. We hypothesized that different myocardial substrates for LV mechanical discoordination exist from (1) electromechanical activation delay, (2) regional differences in contractility, or (3) regional scar and that we could differentiate electromechanical substrates responsive to cardiac resynchronization therapy (CRT) from unresponsive non-electrical substrates. First, we used computer simulations to characterize mechanical discoordination patterns arising from electromechanical and non-electrical substrates and accordingly devise the novel systolic stretch index (SSI), as the sum of posterolateral systolic prestretch and septal systolic rebound stretch. Second, 191 patients with heart failure (QRS duration ≥120 ms; LV ejection fraction ≤35%) had baseline SSI quantified by automated echocardiographic radial strain analysis. Patients with SSI≥9.7% had significantly less heart failure hospitalizations or deaths 2 years after CRT (hazard ratio, 0.32; 95% confidence interval, 0.19-0.53; P<0.001) and less deaths, transplants, or LV assist devices (hazard ratio, 0.28; 95% confidence interval, 0.15-0.55; P<0.001). Furthermore, in a subgroup of 113 patients with intermediate electrocardiographic criteria (QRS duration of 120-149 ms or non-left bundle branch block), SSI≥9.7% was independently associated with significantly less heart failure hospitalizations or deaths (hazard ratio, 0.41; 95% confidence interval, 0.23-0.79; P=0.004) and less deaths, transplants, or LV assist devices (hazard ratio, 0.27; 95% confidence interval, 0.12-0.60; P=0.001). Computer simulations differentiated patterns of LV mechanical discoordination caused by electromechanical substrates responsive to CRT from those related to regional hypocontractility or scar unresponsive to CRT. The novel SSI identified patients who benefited more favorably from CRT, including those with intermediate electrocardiographic criteria, where CRT response is less certain by ECG alone. © 2015 American Heart Association, Inc.

Patterns of neural activity associated with differential acute locomotor stimulation to cocaine and methamphetamine in adolescent versus adult male C57BL/6J mice

PubMed Central

Zombeck, Jonathan A.; Lewicki, Aaron D.; Patel, Kevin; Gupta, Tripta; Rhodes, Justin S.

2009-01-01

Adolescence is a time period when major changes occur in the brain with long-term consequences for behavior. One ramification is altered responses to drugs of abuse, but the specific brain mechanisms and implications for mental health are poorly understood. Here, we used a mouse model in which adolescents display dramatically reduced sensitivity to the acute locomotor stimulating effects of cocaine and methamphetamine. The goal was to identify key brain regions or circuits involved in the differential behavior. Male adolescent (PN 30–35) and young adult (PN 69–74) C57BL/6J mice were administered an intraperitoneal injection of cocaine (0, 15, 30 mg/kg) or methamphetamine (0, 2, 4 mg/kg) and euthanized 90 minutes later. Locomotor activity was monitored continuously in the home cage by video tracking. Immunohistochemical detection of Fos protein was used to quantify neuronal activation in 16 different brain regions. As expected, adolescents were less sensitive to the locomotor stimulating effects of cocaine and methamphetamine as indicated by a rightward shift in the dose response relationship. After a saline injection, adolescents showed similar levels of Fos as adults in all regions except the dorsal and lateral caudate where levels were lower in adolescents. Cocaine and methamphetamine dose dependently increased Fos in all brain regions sampled in both adolescents and adults, but Fos levels were similar in both age groups for a majority of regions and doses. Locomotor activity was correlated with Fos in several brain areas within adolescent and adult groups, and adolescents had a significantly greater induction of Fos for a given amount of locomotor activity in key brain regions including the caudate where they showed reduced Fos under baseline conditions. Future research will identify the molecular and cellular events that are responsible for the differential psychostimulant-induced patterns of brain activation and behavior observed in adolescent versus adult mice. PMID:19932887

Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress.

PubMed

Vialou, Vincent; Thibault, Mackenzie; Kaska, Sophia; Cooper, Sarah; Gajewski, Paula; Eagle, Andrew; Mazei-Robison, Michelle; Nestler, Eric J; Robison, A J

2015-12-01

Major depressive disorder is thought to arise in part from dysfunction of the brain's "reward circuitry", consisting of the mesolimbic dopamine system and the glutamatergic and neuromodulatory inputs onto this system. Both chronic stress and antidepressant treatment regulate gene transcription in many of the brain regions that make up these circuits, but the exact nature of the transcription factors and target genes involved in these processes remain unclear. Here, we demonstrate induction of the FosB family of transcription factors in ∼25 distinct regions of adult mouse brain, including many parts of the reward circuitry, by chronic exposure to the antidepressant fluoxetine. We further uncover specific patterns of FosB gene product expression (i.e., differential expression of full-length FosB, ΔFosB, and Δ2ΔFosB) in brain regions associated with depression--the nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus--in response to chronic fluoxetine treatment, and contrast these patterns with differential induction of FosB isoforms in the chronic social defeat stress model of depression with and without fluoxetine treatment. We find that chronic fluoxetine, in contrast to stress, causes induction of the unstable full-length FosB isoform in the NAc, PFC, and hippocampus even 24 h following the final injection, indicating that these brain regions may undergo chronic activation when fluoxetine is on board, even in the absence of stress. We also find that only the stable ΔFosB isoform correlates with behavioral responses to stress. These data suggest that NAc, PFC, and hippocampus may present useful targets for directed intervention in mood disorders (ie, brain stimulation or gene therapy), and that determining the gene targets of FosB-mediated transcription in these brain regions in response to fluoxetine may yield novel inroads for pharmaceutical intervention in depressive disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Discrimination of human and dog faces and inversion responses in domestic dogs (Canis familiaris).

PubMed

Racca, Anaïs; Amadei, Eleonora; Ligout, Séverine; Guo, Kun; Meints, Kerstin; Mills, Daniel

2010-05-01

Although domestic dogs can respond to many facial cues displayed by other dogs and humans, it remains unclear whether they can differentiate individual dogs or humans based on facial cues alone and, if so, whether they would demonstrate the face inversion effect, a behavioural hallmark commonly used in primates to differentiate face processing from object processing. In this study, we first established the applicability of the visual paired comparison (VPC or preferential looking) procedure for dogs using a simple object discrimination task with 2D pictures. The animals demonstrated a clear looking preference for novel objects when simultaneously presented with prior-exposed familiar objects. We then adopted this VPC procedure to assess their face discrimination and inversion responses. Dogs showed a deviation from random behaviour, indicating discrimination capability when inspecting upright dog faces, human faces and object images; but the pattern of viewing preference was dependent upon image category. They directed longer viewing time at novel (vs. familiar) human faces and objects, but not at dog faces, instead, a longer viewing time at familiar (vs. novel) dog faces was observed. No significant looking preference was detected for inverted images regardless of image category. Our results indicate that domestic dogs can use facial cues alone to differentiate individual dogs and humans and that they exhibit a non-specific inversion response. In addition, the discrimination response by dogs of human and dog faces appears to differ with the type of face involved.

Parallel epigenomic and transcriptomic responses to viral infection in honey bees (Apis mellifera).

PubMed

Galbraith, David A; Yang, Xingyu; Niño, Elina Lastro; Yi, Soojin; Grozinger, Christina

2015-03-01

Populations of honey bees are declining throughout the world, with US beekeepers losing 30% of their colonies each winter. Though multiple factors are driving these colony losses, it is increasingly clear that viruses play a major role. However, information about the molecular mechanisms mediating antiviral immunity in honey bees is surprisingly limited. Here, we examined the transcriptional and epigenetic (DNA methylation) responses to viral infection in honey bee workers. One-day old worker honey bees were fed solutions containing Israeli Acute Paralysis Virus (IAPV), a virus which causes muscle paralysis and death and has previously been associated with colony loss. Uninfected control and infected, symptomatic bees were collected within 20-24 hours after infection. Worker fat bodies, the primary tissue involved in metabolism, detoxification and immune responses, were collected for analysis. We performed transcriptome- and bisulfite-sequencing of the worker fat bodies to identify genome-wide gene expression and DNA methylation patterns associated with viral infection. There were 753 differentially expressed genes (FDR<0.05) in infected versus control bees, including several genes involved in epigenetic and antiviral pathways. DNA methylation status of 156 genes (FDR<0.1) changed significantly as a result of the infection, including those involved in antiviral responses in humans. There was no significant overlap between the significantly differentially expressed and significantly differentially methylated genes, and indeed, the genomic characteristics of these sets of genes were quite distinct. Our results indicate that honey bees have two distinct molecular pathways, mediated by transcription and methylation, that modulate protein levels and/or function in response to viral infections.

RNA-Seq Transcriptome Profiling of Upland Cotton (Gossypium hirsutum L.) Root Tissue under Water-Deficit Stress

PubMed Central

Bowman, Megan J.; Park, Wonkeun; Bauer, Philip J.; Udall, Joshua A.; Page, Justin T.; Raney, Joshua; Scheffler, Brian E.; Jones, Don. C.; Campbell, B. Todd

2013-01-01

An RNA-Seq experiment was performed using field grown well-watered and naturally rain fed cotton plants to identify differentially expressed transcripts under water-deficit stress. Our work constitutes the first application of the newly published diploid D5 Gossypium raimondii sequence in the study of tetraploid AD1 upland cotton RNA-seq transcriptome analysis. A total of 1,530 transcripts were differentially expressed between well-watered and water-deficit stressed root tissues, in patterns that confirm the accuracy of this technique for future studies in cotton genomics. Additionally, putative sequence based genome localization of differentially expressed transcripts detected A2 genome specific gene expression under water-deficit stress. These data will facilitate efforts to understand the complex responses governing transcriptomic regulatory mechanisms and to identify candidate genes that may benefit applied plant breeding programs. PMID:24324815

Discovering high-resolution patterns of differential DNA methylation that correlate with gene expression changes

PubMed Central

VanderKraats, Nathan D.; Hiken, Jeffrey F.; Decker, Keith F.; Edwards, John R.

2013-01-01

Methylation of the CpG-rich region (CpG island) overlapping a gene’s promoter is a generally accepted mechanism for silencing expression. While recent technological advances have enabled measurement of DNA methylation and expression changes genome-wide, only modest correlations between differential methylation at gene promoters and expression have been found. We hypothesize that stronger associations are not observed because existing analysis methods oversimplify their representation of the data and do not capture the diversity of existing methylation patterns. Recently, other patterns such as CpG island shore methylation and long partially hypomethylated domains have also been linked with gene silencing. Here, we detail a new approach for discovering differential methylation patterns associated with expression change using genome-wide high-resolution methylation data: we represent differential methylation as an interpolated curve, or signature, and then identify groups of genes with similarly shaped signatures and corresponding expression changes. Our technique uncovers a diverse set of patterns that are conserved across embryonic stem cell and cancer data sets. Overall, we find strong associations between these methylation patterns and expression. We further show that an extension of our method also outperforms other approaches by generating a longer list of genes with higher quality associations between differential methylation and expression. PMID:23748561

SNF5 Is an Essential Executor of Epigenetic Regulation during Differentiation

PubMed Central

You, Jueng Soo; De Carvalho, Daniel D.; Dai, Chao; Liu, Minmin; Pandiyan, Kurinji; Zhou, Xianghong J.; Liang, Gangning; Jones, Peter A.

2013-01-01

Nucleosome occupancy controls the accessibility of the transcription machinery to DNA regulatory regions and serves an instructive role for gene expression. Chromatin remodelers, such as the BAF complexes, are responsible for establishing nucleosome occupancy patterns, which are key to epigenetic regulation along with DNA methylation and histone modifications. Some reports have assessed the roles of the BAF complex subunits and stemness in murine embryonic stem cells. However, the details of the relationships between remodelers and transcription factors in altering chromatin configuration, which ultimately affects gene expression during cell differentiation, remain unclear. Here for the first time we demonstrate that SNF5, a core subunit of the BAF complex, negatively regulates OCT4 levels in pluripotent cells and is essential for cell survival during differentiation. SNF5 is responsible for generating nucleosome-depleted regions (NDRs) at the regulatory sites of OCT4 repressed target genes such as PAX6 and NEUROG1, which are crucial for cell fate determination. Concurrently, SNF5 closes the NDRs at the regulatory regions of OCT4-activated target genes such as OCT4 itself and NANOG. Furthermore, using loss- and gain-of-function experiments followed by extensive genome-wide analyses including gene expression microarrays and ChIP-sequencing, we highlight that SNF5 plays dual roles during differentiation by antagonizing the expression of genes that were either activated or repressed by OCT4, respectively. Together, we demonstrate that SNF5 executes the switch between pluripotency and differentiation. PMID:23637628

SNF5 is an essential executor of epigenetic regulation during differentiation.

PubMed

You, Jueng Soo; De Carvalho, Daniel D; Dai, Chao; Liu, Minmin; Pandiyan, Kurinji; Zhou, Xianghong J; Liang, Gangning; Jones, Peter A

2013-04-01

Nucleosome occupancy controls the accessibility of the transcription machinery to DNA regulatory regions and serves an instructive role for gene expression. Chromatin remodelers, such as the BAF complexes, are responsible for establishing nucleosome occupancy patterns, which are key to epigenetic regulation along with DNA methylation and histone modifications. Some reports have assessed the roles of the BAF complex subunits and stemness in murine embryonic stem cells. However, the details of the relationships between remodelers and transcription factors in altering chromatin configuration, which ultimately affects gene expression during cell differentiation, remain unclear. Here for the first time we demonstrate that SNF5, a core subunit of the BAF complex, negatively regulates OCT4 levels in pluripotent cells and is essential for cell survival during differentiation. SNF5 is responsible for generating nucleosome-depleted regions (NDRs) at the regulatory sites of OCT4 repressed target genes such as PAX6 and NEUROG1, which are crucial for cell fate determination. Concurrently, SNF5 closes the NDRs at the regulatory regions of OCT4-activated target genes such as OCT4 itself and NANOG. Furthermore, using loss- and gain-of-function experiments followed by extensive genome-wide analyses including gene expression microarrays and ChIP-sequencing, we highlight that SNF5 plays dual roles during differentiation by antagonizing the expression of genes that were either activated or repressed by OCT4, respectively. Together, we demonstrate that SNF5 executes the switch between pluripotency and differentiation.

Migratory patterns and population structure among breeding and wintering red-breasted mergansers (Mergus serrator) and common mergansers (M. merganser)

USGS Publications Warehouse

Pearce, J.M.; McCracken, K.G.; Christensen, Thomas K.; Zhuravlev, Y.N.

2009-01-01

Philopatry has long been assumed to structure populations of waterfowl and other species of birds genetically, especially via maternally transmitted mitochondrial DNA (mtDNA), yet other migratory behaviors and nesting ecology (use of ground vs. cavity sites) may also contribute to population genetic structure. We investigated the effects of migration and nesting ecology on the population genetic structure of two Holarctic waterfowl, the Red-breasted Merganser (Mergus serrator) and Common Merganser (M. merganser), using mtDNA control-region sequence data. Red-breasted Mergansers (a ground-nesting species) exhibited lower levels of population differentiation across their North American range, possibly as a result of post-Pleistocene range expansion and population growth. By contrast, Common Mergansers (a cavity-nesting species) breeding in western and eastern North America were strongly differentiated, as were continental groups in North America and Europe. Our hypothesis that population differentiation of breeding female Common Mergansers results from limited migration during non-breeding periods was not supported, in that equally heterogeneous mtDNA lineages were observed in males and females on several wintering areas. The interspecific differences in mtDNA patterns for these two closely related species may have resulted from factors related to nesting ecology (ground vs. cavity nesting) and responses to historical climate change.

Autophagy-associated alpha-arrestin signaling is required for conidiogenous cell development in Magnaporthe oryzae.

PubMed

Dong, Bo; Xu, Xiaojin; Chen, Guoqing; Zhang, Dandan; Tang, Mingzhi; Xu, Fei; Liu, Xiaohong; Wang, Hua; Zhou, Bo

2016-08-08

Conidiation patterning is evolutionarily complex and mechanism concerning conidiogenous cell differentiation remains largely unknown. Magnaporthe oryzae conidiates in a sympodial way and uses its conidia to infect host and disseminate blast disease. Arrestins are multifunctional proteins that modulate receptor down-regulation and scaffold components of intracellular trafficking routes. We here report an alpha-arrestin that regulates patterns of conidiation and contributes to pathogenicity in M. oryzae. We show that disruption of ARRDC1 generates mutants which produce conidia in an acropetal array and ARRDC1 significantly affects expression profile of CCA1, a virulence-related transcription factor required for conidiogenous cell differentiation. Although germ tubes normally develop appressoria, penetration peg formation is dramatically impaired and Δarrdc1 mutants are mostly nonpathogenic. Fluorescent analysis indicates that EGFP-ARRDC1 puncta are well colocalized with DsRed2-Atg8, and this distribution profile could not be altered in Δatg9 mutants, suggesting ARRDC1 enters into autophagic flux before autophagosome maturation. We propose that M. oryzae employs ARRDC1 to regulate specific receptors in response to conidiation-related signals for conidiogenous cell differentiation and utilize autophagosomes for desensitization of conidiogenous receptor, which transmits extracellular signal to the downstream elements of transcription factors. Our investigation extends novel significance of autophagy-associated alpha-arrestin signaling to fungal parasites.

Conservation in Mammals of Genes Associated with Aggression-Related Behavioral Phenotypes in Honey Bees

PubMed Central

Robinson, Gene E.; Jakobsson, Eric

2016-01-01

The emerging field of sociogenomics explores the relations between social behavior and genome structure and function. An important question is the extent to which associations between social behavior and gene expression are conserved among the Metazoa. Prior experimental work in an invertebrate model of social behavior, the honey bee, revealed distinct brain gene expression patterns in African and European honey bees, and within European honey bees with different behavioral phenotypes. The present work is a computational study of these previous findings in which we analyze, by orthology determination, the extent to which genes that are socially regulated in honey bees are conserved across the Metazoa. We found that the differentially expressed gene sets associated with alarm pheromone response, the difference between old and young bees, and the colony influence on soldier bees, are enriched in widely conserved genes, indicating that these differences have genomic bases shared with many other metazoans. By contrast, the sets of differentially expressed genes associated with the differences between African and European forager and guard bees are depleted in widely conserved genes, indicating that the genomic basis for this social behavior is relatively specific to honey bees. For the alarm pheromone response gene set, we found a particularly high degree of conservation with mammals, even though the alarm pheromone itself is bee-specific. Gene Ontology identification of human orthologs to the strongly conserved honey bee genes associated with the alarm pheromone response shows overrepresentation of protein metabolism, regulation of protein complex formation, and protein folding, perhaps associated with remodeling of critical neural circuits in response to alarm pheromone. We hypothesize that such remodeling may be an adaptation of social animals to process and respond appropriately to the complex patterns of conspecific communication essential for social organization. PMID:27359102

Conservation in Mammals of Genes Associated with Aggression-Related Behavioral Phenotypes in Honey Bees.

PubMed

Liu, Hui; Robinson, Gene E; Jakobsson, Eric

2016-06-01

The emerging field of sociogenomics explores the relations between social behavior and genome structure and function. An important question is the extent to which associations between social behavior and gene expression are conserved among the Metazoa. Prior experimental work in an invertebrate model of social behavior, the honey bee, revealed distinct brain gene expression patterns in African and European honey bees, and within European honey bees with different behavioral phenotypes. The present work is a computational study of these previous findings in which we analyze, by orthology determination, the extent to which genes that are socially regulated in honey bees are conserved across the Metazoa. We found that the differentially expressed gene sets associated with alarm pheromone response, the difference between old and young bees, and the colony influence on soldier bees, are enriched in widely conserved genes, indicating that these differences have genomic bases shared with many other metazoans. By contrast, the sets of differentially expressed genes associated with the differences between African and European forager and guard bees are depleted in widely conserved genes, indicating that the genomic basis for this social behavior is relatively specific to honey bees. For the alarm pheromone response gene set, we found a particularly high degree of conservation with mammals, even though the alarm pheromone itself is bee-specific. Gene Ontology identification of human orthologs to the strongly conserved honey bee genes associated with the alarm pheromone response shows overrepresentation of protein metabolism, regulation of protein complex formation, and protein folding, perhaps associated with remodeling of critical neural circuits in response to alarm pheromone. We hypothesize that such remodeling may be an adaptation of social animals to process and respond appropriately to the complex patterns of conspecific communication essential for social organization.

Biological variations in depression and anxiety between East and West.

PubMed

Chen, Po-Yu; Wang, Sheng-Chang; Poland, Russell E; Lin, Keh-Ming

2009-01-01

Ethnicity and culture represent important factors in shaping psychopathology as well as pharmacotherapeutic responses in psychiatric patients. A large body of literature, accumulated over the past several decades, demonstrates that these factors not only determine the metabolism and disposition of medications (pharmacokinetics), but also their interactions with therapeutic targets (pharmacodynamics). This article focuses on the impact of such variations on the diagnosis and treatment of depression and anxiety disorders between East and West. Genes controlling the expression of drug metabolizing enzymes as well as the function of the brain are highly polymorphic, and the patterns and distribution of these polymorphisms are typically divergent across ethnic groups. To the extent that these genetic patterns determine drug response, ethnic variations in these genetic dispositions will lead to differential responses in clinical settings. In addition, the expression of these genes is significantly influenced by environmental factors including diet as well as exposure to other natural products. Superimposed on these biological influences, culturally determined beliefs and behavioral patterns also profoundly influence patients' expectations of treatment response, adherence, and interactions with clinicians. In addition to pharmacotherapeutic responses, emerging data also indicate that significant ethnic variations exist in genetic polymorphisms and neurobiologic correlates (biomarkers) that may be associated with the vulnerability to psychiatric disorders. These considerations argue for the importance of examining biological variations across ethnic groups, especially in the clinical context, in terms of the assessment and treatment of psychiatric patients, and in our understanding of psychiatric phenomenology and nosology.

Acoustic differentiation and behavioral response reveals cryptic species within Buergeria treefrogs (Anura, Rhacophoridae) from Taiwan

PubMed Central

Wang, Ying-Han; Tseng, Hui-Yun; Lin, Yen-Po; Komaki, Shohei

2017-01-01

Buergeria japonica is a widely distributed treefrog occurring from Ryukyu Archipelago to Taiwan. Across this wide distributional range, we combined molecular, acoustic, morphological, and behavioral characters to clarify the taxonomic status among these insular populations. Genetic differentiation in mitochondrial sequences indicated an over 16% divergence among two deeply divergent clades: Japanese clade distributes in Ryukyu Archipelago and northwestern drainages of Taiwan, while Taiwanese clade distributes in the remaining drainages on Taiwan. The Taiwanese clade can be distinguished from the nominative species not only by molecular and morphological differences, but also distinguishable by considerable acoustic differentiation, which is extraordinarily noticeable for an additional type of long call that never recorded from Japanese clade. The two clades form a parapatric distribution pattern with narrow contact zones both in western and eastern Taiwan. Playback experiments indicated that male frogs show significantly stronger defensiveness against conspecific calls rather than heterospecific calls, indicating that these signals play a crucial role in species recognition. Here we describe the Taiwanese clade as a new species; the behavioral response and the magnitude of gene flow across their contact zones are especially worth for detailed studies. PMID:28877201

Proteome analysis of Physcomitrella patens exposed to progressive dehydration and rehydration.

PubMed

Cui, Suxia; Hu, Jia; Guo, Shilei; Wang, Jie; Cheng, Yali; Dang, Xinxing; Wu, Lili; He, Yikun

2012-01-01

Physcomitrella patens is an extremely dehydration-tolerant moss. However, the molecular basis of its responses to loss of cellular water remains unclear. A comprehensive proteomic analysis of dehydration- and rehydration-responsive proteins has been conducted using quantitative two-dimensional difference in-gel electrophoresis (2D-DIGE), and traditional 2-D gel electrophoresis (2-DE) combined with MALDI TOF/TOF MS. Of the 216 differentially-expressed protein spots, 112 and 104 were dehydration- and rehydration-responsive proteins, respectively. The functional categories of the most differentially-expressed proteins were seed maturation, defence, protein synthesis and quality control, and energy production. Strikingly, most of the late embryogenesis abundant (LEA) proteins were expressed at a basal level under control conditions and their synthesis was strongly enhanced by dehydration, a pattern that was confirmed by RT-PCR. Actinoporins, phosphatidylethanolamine-binding protein, arabinogalactan protein, and phospholipase are the likely dominant players in the defence system. In addition, 24 proteins of unknown function were identified as novel dehydration- or rehydration-responsive proteins. Our data indicate that Physcomitrella adopts a rapid protein response mechanism to cope with dehydration in its leafy-shoot and basal expression levels of desiccation-tolerant proteins are rapidly upgraded at high levels under stress. This mechanism appears similar to that seen in angiosperm seeds.

Proteome analysis of Physcomitrella patens exposed to progressive dehydration and rehydration

PubMed Central

Cui, Suxia; Hu, Jia; Guo, Shilei; Wang, Jie; Cheng, Yali; Dang, Xinxing; Wu, Lili; He, Yikun

2012-01-01

Physcomitrella patens is an extremely dehydration-tolerant moss. However, the molecular basis of its responses to loss of cellular water remains unclear. A comprehensive proteomic analysis of dehydration- and rehydration-responsive proteins has been conducted using quantitative two-dimensional difference in-gel electrophoresis (2D-DIGE), and traditional 2-D gel electrophoresis (2-DE) combined with MALDI TOF/TOF MS. Of the 216 differentially-expressed protein spots, 112 and 104 were dehydration- and rehydration-responsive proteins, respectively. The functional categories of the most differentially-expressed proteins were seed maturation, defence, protein synthesis and quality control, and energy production. Strikingly, most of the late embryogenesis abundant (LEA) proteins were expressed at a basal level under control conditions and their synthesis was strongly enhanced by dehydration, a pattern that was confirmed by RT-PCR. Actinoporins, phosphatidylethanolamine-binding protein, arabinogalactan protein, and phospholipase are the likely dominant players in the defence system. In addition, 24 proteins of unknown function were identified as novel dehydration- or rehydration-responsive proteins. Our data indicate that Physcomitrella adopts a rapid protein response mechanism to cope with dehydration in its leafy-shoot and basal expression levels of desiccation-tolerant proteins are rapidly upgraded at high levels under stress. This mechanism appears similar to that seen in angiosperm seeds. PMID:21994173

Metabolomic responses to lumacaftor/ivacaftor in cystic fibrosis.

PubMed

Kopp, Benjamin T; McCulloch, Scott; Shrestha, Chandra L; Zhang, Shuzhong; Sarzynski, Lisa; Woodley, Frederick W; Hayes, Don

2018-05-01

Cystic fibrosis (CF) is a life-limiting disease caused by a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Lumacaftor/Ivacaftor is a novel CFTR modulator approved for patients that are homozygous for Phe508del CFTR, but its clinical effectiveness varies amongst patients, making it difficult to determine clinical responders. Therefore, identifying biochemical biomarkers associated with drug response are clinically important for follow-up studies. Serum metabolomics was performed on twenty patients with CF pre- and 6-month post-Lumacaftor/Ivacaftor response via Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Correlation with clinical variables was performed. Metabolomics analysis demonstrated 188 differentially regulated metabolites between patients pre- and post-Lumacaftor/Ivacaftor initiation, with a predominance of lipid and amino acid alterations. The top 30 metabolites were able to differentiate pre- and post-Lumacaftor/Ivacaftor status in greater than 90% of patients via a random-forest confusion matrix. Alterations in bile acids, phospholipids, and bacteria-associated metabolites were the predominant changes associated with drug response. Importantly, changes in metabolic patterns were associated with clinical responders. Selected key lipid and amino acid metabolic pathways were significantly affected by Lumacaftor/Ivacaftor initiation and similar pathways were affected in clinical responders. Targeted metabolomics may provide useful and relevant biomarkers of CFTR modulator responses. © 2018 Wiley Periodicals, Inc.

Microglia Transcriptome Changes in a Model of Depressive Behavior after Immune Challenge

PubMed Central

Gonzalez-Pena, Dianelys; Nixon, Scott E.; O’Connor, Jason C.; Southey, Bruce R.; Lawson, Marcus A.; McCusker, Robert H.; Borras, Tania; Machuca, Debbie; Hernandez, Alvaro G.; Dantzer, Robert; Kelley, Keith W.; Rodriguez-Zas, Sandra L.

2016-01-01

Depression symptoms following immune response to a challenge have been reported after the recovery from sickness. A RNA-Seq study of the dysregulation of the microglia transcriptome in a model of inflammation-associated depressive behavior was undertaken. The transcriptome of microglia from mice at day 7 after Bacille Calmette Guérin (BCG) challenge was compared to that from unchallenged Control mice and to the transcriptome from peripheral macrophages from the same mice. Among the 562 and 3,851 genes differentially expressed between BCG-challenged and Control mice in microglia and macrophages respectively, 353 genes overlapped between these cells types. Among the most differentially expressed genes in the microglia, serum amyloid A3 (Saa3) and cell adhesion molecule 3 (Cadm3) were over-expressed and coiled-coil domain containing 162 (Ccdc162) and titin-cap (Tcap) were under-expressed in BCG-challenged relative to Control. Many of the differentially expressed genes between BCG-challenged and Control mice were associated with neurological disorders encompassing depression symptoms. Across cell types, S100 calcium binding protein A9 (S100A9), interleukin 1 beta (Il1b) and kynurenine 3-monooxygenase (Kmo) were differentially expressed between challenged and control mice. Immune response, chemotaxis, and chemokine activity were among the functional categories enriched by the differentially expressed genes. Functional categories enriched among the 9,117 genes differentially expressed between cell types included leukocyte regulation and activation, chemokine and cytokine activities, MAP kinase activity, and apoptosis. More than 200 genes exhibited alternative splicing events between cell types including WNK lysine deficient protein kinase 1 (Wnk1) and microtubule-actin crosslinking factor 1(Macf1). Network visualization revealed the capability of microglia to exhibit transcriptome dysregulation in response to immune challenge still after resolution of sickness symptoms, albeit lower than that observed in macrophages. The persistent transcriptome dysregulation in the microglia shared patterns with neurological disorders indicating that the associated persistent depressive symptoms share a common transcriptome basis. PMID:26959683

Microglia Transcriptome Changes in a Model of Depressive Behavior after Immune Challenge.

PubMed

Gonzalez-Pena, Dianelys; Nixon, Scott E; O'Connor, Jason C; Southey, Bruce R; Lawson, Marcus A; McCusker, Robert H; Borras, Tania; Machuca, Debbie; Hernandez, Alvaro G; Dantzer, Robert; Kelley, Keith W; Rodriguez-Zas, Sandra L

2016-01-01

Depression symptoms following immune response to a challenge have been reported after the recovery from sickness. A RNA-Seq study of the dysregulation of the microglia transcriptome in a model of inflammation-associated depressive behavior was undertaken. The transcriptome of microglia from mice at day 7 after Bacille Calmette Guérin (BCG) challenge was compared to that from unchallenged Control mice and to the transcriptome from peripheral macrophages from the same mice. Among the 562 and 3,851 genes differentially expressed between BCG-challenged and Control mice in microglia and macrophages respectively, 353 genes overlapped between these cells types. Among the most differentially expressed genes in the microglia, serum amyloid A3 (Saa3) and cell adhesion molecule 3 (Cadm3) were over-expressed and coiled-coil domain containing 162 (Ccdc162) and titin-cap (Tcap) were under-expressed in BCG-challenged relative to Control. Many of the differentially expressed genes between BCG-challenged and Control mice were associated with neurological disorders encompassing depression symptoms. Across cell types, S100 calcium binding protein A9 (S100A9), interleukin 1 beta (Il1b) and kynurenine 3-monooxygenase (Kmo) were differentially expressed between challenged and control mice. Immune response, chemotaxis, and chemokine activity were among the functional categories enriched by the differentially expressed genes. Functional categories enriched among the 9,117 genes differentially expressed between cell types included leukocyte regulation and activation, chemokine and cytokine activities, MAP kinase activity, and apoptosis. More than 200 genes exhibited alternative splicing events between cell types including WNK lysine deficient protein kinase 1 (Wnk1) and microtubule-actin crosslinking factor 1(Macf1). Network visualization revealed the capability of microglia to exhibit transcriptome dysregulation in response to immune challenge still after resolution of sickness symptoms, albeit lower than that observed in macrophages. The persistent transcriptome dysregulation in the microglia shared patterns with neurological disorders indicating that the associated persistent depressive symptoms share a common transcriptome basis.

Understanding the molecular aspects of oriental obesity pattern differentiation using DNA microarray.

PubMed

Hong, Sun Woo; Yoo, Jae-Wook; Bose, Shambhunath; Park, Jung-Hyun; Han, Kyungsun; Kim, Soyoun; Lim, Chi-Yeon; Kim, Hojun; Lee, Dong-Ki

2015-10-19

Human constitution, the fundamental basis of oriental medicine, is categorized into different patterns for a particular disease according to the physical, physiological, and clinical characteristics of the individuals. Obesity, a condition of metabolic disorder, is classified according to six patterns in oriental medicine, as follows: spleen deficiency syndrome, phlegm fluid syndrome, yang deficiency syndrome (YDS), food accumulation syndrome (FAS), liver depression syndrome (LDS), and blood stasis syndrome. In oriental medicine, identification of the disease pattern for individual obese patients is performed on the basis of differentiation in obesity syndrome index and, accordingly, personalized treatment is provided to the patients. The aim of the current study was to understand the obesity patterns in oriental medicine from the genomic point of view via determining the gene expression signature of obese patients using peripheral blood mononuclear cells as the samples. The study was conducted in 23 South Korean obese subjects (19 female and four male) with BMI ≥25 kg/m(2). Identification of oriental obesity pattern was based on the software-guided evaluation of the responses of the subjects to a questionnaire developed by the Korean Institute of Oriental Medicine. The expression profiles of genes were determined using DNA microarray and the level of transcription of genes of interest was further evaluated using quantitative real-time PCR (qRT-PCR). Gene clustering analysis of the microarray data from the FAS, LDS, and YDS subjects exhibited disease pattern-specific upregulation of expression of several genes in a particular cluster. Further analysis of transcription of selected genes using qRT-PCR led to identification of specific genes, including prostaglandin endoperoxide synthase 2, G0/G1 switch 2, carcinoembryonic antigen-related cell adhesion molecule 3, cystein-serine-rich nuclear protein 1, and interleukin 8 receptor, alpha which were highly expressed in LDS obesity constitution. Our current study can be considered as a valuable contribution to the understanding of possible explanation for obesity pattern differentiation in oriental medicine. Further studies can address a novel possibility that the genomic and oriental empirical approaches can be combined and implemented in systematic and synergistic development of personalized medicine. This clinical trial was registered in Clinical Research Information Service of Korea National Institute of Health ( https://cris.nih.go.kr/cris/index.jsp ). KCT0000387.

The way to her heart? Response to romantic cues is dependent on hunger state and dieting history: An fMRI pilot study.

PubMed

Ely, Alice V; Childress, Anna Rose; Jagannathan, Kanchana; Lowe, Michael R

2015-12-01

Normal weight historical dieters (HDs) are prone to future weight gain, and show higher levels of brain activation in reward-related regions after having eaten than nondieters (NDs) in response to food stimuli (Ely, Childress, Jagannathan, & Lowe, 2014), a similar pattern to that seen in obesity. We hypothesized that HDs are differentially sensitive after eating to rewards in general, and thus extended prior findings by comparing the same groups' brain activation when viewing romantic pictures compared to neutral stimuli while being scanned in a blood oxygenation level-dependent (BOLD) fMRI paradigm in a fasted and fed state. Results show that 1) in fed relative to fasted conditions, both HDs and NDs were more responsive in areas related to reward and 2) in HDs, greater fed versus fasted activation extended to areas linked to perception and goal-directed behavior. HDs relative to NDs were more responsive to romantic cues in the superior frontal gyrus when fasted and the middle temporal gyrus when fed. This pattern of response is similar to HDs' activation when viewing highly palatable food cues, and is consistent with research showing overlapping brain-based responses to sex, drugs and food. Copyright © 2015 Elsevier Ltd. All rights reserved.

Probing thyroglobulin in undiluted human serum based on pattern recognition and competitive adsorption of proteins

NASA Astrophysics Data System (ADS)

Wang, Ran; Huang, Shuai; Li, Jing; Chae, Junseok

2014-10-01

Thyroglobulin (Tg) is a sensitive indicator of persistent or recurrent differentiated thyroid cancer of follicular cell origin. Detection of Tg in human serum is challenging as bio-receptors, such as anti-Tg, used in immunoassay have relatively weak binding affinity. We engineer sensing surfaces using the competitive adsorption of proteins, termed the Vroman Effect. Coupled with Surface Plasmon Resonance, the "cross-responsive" interactions of Tg on the engineered surfaces produce uniquely distinguishable multiple signature patterns, which are discriminated using Linear Discriminant Analysis. Tg-spiked samples, down to 2 ng/ml Tg in undiluted human serum, are sensitively and selectively discriminated from the control (undiluted human serum).

Genomic architecture of adaptive color pattern divergence and convergence in Heliconius butterflies

PubMed Central

Supple, Megan A.; Hines, Heather M.; Dasmahapatra, Kanchon K.; Lewis, James J.; Nielsen, Dahlia M.; Lavoie, Christine; Ray, David A.; Salazar, Camilo; McMillan, W. Owen; Counterman, Brian A.

2013-01-01

Identifying the genetic changes driving adaptive variation in natural populations is key to understanding the origins of biodiversity. The mosaic of mimetic wing patterns in Heliconius butterflies makes an excellent system for exploring adaptive variation using next-generation sequencing. In this study, we use a combination of techniques to annotate the genomic interval modulating red color pattern variation, identify a narrow region responsible for adaptive divergence and convergence in Heliconius wing color patterns, and explore the evolutionary history of these adaptive alleles. We use whole genome resequencing from four hybrid zones between divergent color pattern races of Heliconius erato and two hybrid zones of the co-mimic Heliconius melpomene to examine genetic variation across 2.2 Mb of a partial reference sequence. In the intergenic region near optix, the gene previously shown to be responsible for the complex red pattern variation in Heliconius, population genetic analyses identify a shared 65-kb region of divergence that includes several sites perfectly associated with phenotype within each species. This region likely contains multiple cis-regulatory elements that control discrete expression domains of optix. The parallel signatures of genetic differentiation in H. erato and H. melpomene support a shared genetic architecture between the two distantly related co-mimics; however, phylogenetic analysis suggests mimetic patterns in each species evolved independently. Using a combination of next-generation sequencing analyses, we have refined our understanding of the genetic architecture of wing pattern variation in Heliconius and gained important insights into the evolution of novel adaptive phenotypes in natural populations. PMID:23674305

Differential reward network functional connectivity in cannabis dependent and non-dependent users☆

PubMed Central

Filbey, Francesca M.; Dunlop, Joseph

2015-01-01

Background Emergent studies show that similar to other substances of abuse, cue-reactivity to cannabis is also associated with neural response in the brain’s reward pathway (Filbey et al., 2009). However, the inter-relatedness of brain regions during cue-reactivity in cannabis users remains unknown. Methods In this study, we conducted a series of investigations to determine functional connectivity during cue-reactivity in 71 cannabis users. First, we used psychophysiological interaction (PPI) analysis to examine coherent neural response to cannabis cues. Second, we evaluated whether these patterns of network functional connectivity differentiated dependent and non-dependent users. Finally, as an exploratory analysis, we determined the directionality of these connections via Granger connectivity analyses. Results PPI analyses showed reward network functional connectivity with the nucleus accumbens (NAc) seed region during cue exposure. Between-group contrasts found differential effects of dependence status. Dependent users (N = 31) had greater functional connectivity with amygdala and anterior cingulate gyrus (ACG) seeds while the non-dependent users (N = 24) had greater functional connectivity with the NAc, orbitofrontal cortex (OFC) and hippocampus seeds. Granger analyses showed that hippocampal and ACG activation preceded neural response in reward areas. Conclusions Both PPI and Granger analyses demonstrated strong functional coherence in reward regions during exposure to cannabis cues in current cannabis users. Functional connectivity (but not regional activation) in the reward network differentiated dependent from non-dependent cannabis users. Our findings suggest that repeated cannabis exposure causes observable changes in functional connectivity in the reward network and should be considered in intervention strategies. PMID:24838032

Differential associations between sensory response patterns and language, social, and communication measures in children with autism or other developmental disabilities.

PubMed

Watson, Linda R; Patten, Elena; Baranek, Grace T; Poe, Michele; Boyd, Brian A; Freuler, Ashley; Lorenzi, Jill

2011-12-01

To examine patterns of sensory responsiveness (i.e., hyperresponsiveness, hyporesponsiveness, and sensory seeking) as factors that may account for variability in social-communicative symptoms of autism and variability in language, social, and communication skill development in children with autism or other developmental disabilities (DDs). Children with autistic disorder (AD; n = 72, mean age = 52.3 months) and other DDs (n = 44, mean age = 48.1 months) participated in a protocol measuring sensory response patterns; social-communicative symptoms of autism; and language, social, and communication skills. Hyporesponsiveness was positively associated with social-communicative symptom severity, with no significant group difference in the association. Hyperresponsiveness was not significantly associated with social-communicative symptom severity. A group difference emerged for sensory seeking and social-communicative symptom severity, with a positive association for the AD group only. For the 2 groups of children combined, hyporesponsiveness was negatively associated with language skills and social adaptive skills. Sensory seeking also was negatively associated with language skills. These associations did not differ between the 2 groups. Aberrant sensory processing may play an important role in the pathogenesis of autism and other DDs as well as in the rate of acquisition of language, social, and communication skills.

Differential Associations between Sensory Response Patterns and Language, Social, and Communication Measures in Children with Autism or Other Developmental Disabilities

PubMed Central

Watson, Linda R.; Patten, Elena; Baranek, Grace T.; Poe, Michele; Boyd, Brian A.; Freuler, Ashley; Lorenzi, Jill

2012-01-01

Purpose Examine patterns of sensory responsiveness (i.e., hyperresponsiveness, hyporesponsiveness, and sensory seeking) as factors that may account for variability in social-communicative symptoms of autism and variability in language, social, and communication skill development in children with autism or other developmental disabilities. Method Children with autistic disorder (AD; n = 72, mean age = 52.3 months) and other developmental disabilities (DD; n = 44, mean age = 48.1 months) participated in a protocol measuring sensory response patterns, social-communicative symptoms of autism, and language, social, and communication skills. Results Hyporesponsiveness was positively associated with social-communicative symptom severity, with no significant group difference in the association. Hyperresponsiveness was not significantly associated with social-communicative symptom severity. A group difference emerged for sensory seeking and social-communicative symptom severity, with a positive association for the AD group only. For the two groups of children combined, hyporesponsiveness was negatively associated with language skills and social adaptive skills. Sensory seeking also was negatively associated with language skills. These associations did not differ between the two groups. Conclusions Aberrant sensory processing may play an important role in the pathogenesis of autism and other developmental disabilities, as well as in the rate of acquisition of language, social, and communication skills. PMID:21862675

Differential expression patterns of housekeeping genes increase diagnostic and prognostic value in lung cancer

PubMed Central

Chang, Yu-Chun; Ding, Yan; Dong, Lingsheng; Zhu, Lang-Jing; Jensen, Roderick V.

2018-01-01

Background Using DNA microarrays, we previously identified 451 genes expressed in 19 different human tissues. Although ubiquitously expressed, the variable expression patterns of these “housekeeping genes” (HKGs) could separate one normal human tissue type from another. Current focus on identifying “specific disease markers” is problematic as single gene expression in a given sample represents the specific cellular states of the sample at the time of collection. In this study, we examine the diagnostic and prognostic potential of the variable expressions of HKGs in lung cancers. Methods Microarray and RNA-seq data for normal lungs, lung adenocarcinomas (AD), squamous cell carcinomas of the lung (SQCLC), and small cell carcinomas of the lung (SCLC) were collected from online databases. Using 374 of 451 HKGs, differentially expressed genes between pairs of sample types were determined via two-sided, homoscedastic t-test. Principal component analysis and hierarchical clustering classified normal lung and lung cancers subtypes according to relative gene expression variations. We used uni- and multi-variate cox-regressions to identify significant predictors of overall survival in AD patients. Classifying genes were selected using a set of training samples and then validated using an independent test set. Gene Ontology was examined by PANTHER. Results This study showed that the differential expression patterns of 242, 245, and 99 HKGs were able to distinguish normal lung from AD, SCLC, and SQCLC, respectively. From these, 70 HKGs were common across the three lung cancer subtypes. These HKGs have low expression variation compared to current lung cancer markers (e.g., EGFR, KRAS) and were involved in the most common biological processes (e.g., metabolism, stress response). In addition, the expression pattern of 106 HKGs alone was a significant classifier of AD versus SQCLC. We further highlighted that a panel of 13 HKGs was an independent predictor of overall survival and cumulative risk in AD patients. Discussion Here we report HKG expression patterns may be an effective tool for evaluation of lung cancer states. For example, the differential expression pattern of 70 HKGs alone can separate normal lung tissue from various lung cancers while a panel of 106 HKGs was a capable class predictor of subtypes of non-small cell carcinomas. We also reported that HKGs have significantly lower variance compared to traditional cancer markers across samples, highlighting the robustness of a panel of genes over any one specific biomarker. Using RNA-seq data, we showed that the expression pattern of 13 HKGs is a significant, independent predictor of overall survival for AD patients. This reinforces the predictive power of a HKG panel across different gene expression measurement platforms. Thus, we propose the expression patterns of HKGs alone may be sufficient for the diagnosis and prognosis of individuals with lung cancer. PMID:29761043

Genome-wide analysis of the interaction between the endosymbiotic bacterium Wolbachia and its Drosophila host.

PubMed

Xi, Zhiyong; Gavotte, Laurent; Xie, Yan; Dobson, Stephen L

2008-01-02

Intracellular Wolbachia bacteria are obligate, maternally-inherited, endosymbionts found frequently in insects and other invertebrates. The success of Wolbachia can be attributed in part to an ability to alter host reproduction via mechanisms including cytoplasmic incompatibility (CI), parthenogenesis, feminization and male killing. Despite substantial scientific effort, the molecular mechanisms underlying the Wolbachia/host interaction are unknown. Here, an in vitro Wolbachia infection was generated in the Drosophila S2 cell line, and transcription profiles of infected and uninfected cells were compared by microarray. Differentially-expressed patterns related to reproduction, immune response and heat stress response are observed, including multiple genes that have been previously reported to be involved in the Wolbachia/host interaction. Subsequent in vivo characterization of differentially-expressed products in gonads demonstrates that Angiotensin Converting Enzyme (Ance) varies between Wolbachia infected and uninfected flies and that the variation occurs in a sex-specific manner. Consistent with expectations for the conserved CI mechanism, the observed Ance expression pattern is repeatable in different Drosophila species and with different Wolbachia types. To examine Ance involvement in the CI phenotype, compatible and incompatible crosses of Ance mutant flies were conducted. Significant differences are observed in the egg hatch rate resulting from incompatible crosses, providing support for additional experiments examining for an interaction of Ance with the CI mechanism. Wolbachia infection is shown to affect the expression of multiple host genes, including Ance. Evidence for potential Ance involvement in the CI mechanism is described, including the prior report of Ance in spermatid differentiation, Wolbachia-induced sex-specific effects on Ance expression and an Ance mutation effect on CI levels. The results support the use of Wolbachia infected cell cultures as an appropriate model for predicting in vivo host/Wolbachia interactions.

Genome-wide analysis of the interaction between the endosymbiotic bacterium Wolbachia and its Drosophila host

PubMed Central

Xi, Zhiyong; Gavotte, Laurent; Xie, Yan; Dobson, Stephen L

2008-01-01

Background Intracellular Wolbachia bacteria are obligate, maternally-inherited, endosymbionts found frequently in insects and other invertebrates. The success of Wolbachia can be attributed in part to an ability to alter host reproduction via mechanisms including cytoplasmic incompatibility (CI), parthenogenesis, feminization and male killing. Despite substantial scientific effort, the molecular mechanisms underlying the Wolbachia/host interaction are unknown. Results Here, an in vitro Wolbachia infection was generated in the Drosophila S2 cell line, and transcription profiles of infected and uninfected cells were compared by microarray. Differentially-expressed patterns related to reproduction, immune response and heat stress response are observed, including multiple genes that have been previously reported to be involved in the Wolbachia/host interaction. Subsequent in vivo characterization of differentially-expressed products in gonads demonstrates that Angiotensin Converting Enzyme (Ance) varies between Wolbachia infected and uninfected flies and that the variation occurs in a sex-specific manner. Consistent with expectations for the conserved CI mechanism, the observed Ance expression pattern is repeatable in different Drosophila species and with different Wolbachia types. To examine Ance involvement in the CI phenotype, compatible and incompatible crosses of Ance mutant flies were conducted. Significant differences are observed in the egg hatch rate resulting from incompatible crosses, providing support for additional experiments examining for an interaction of Ance with the CI mechanism. Conclusion Wolbachia infection is shown to affect the expression of multiple host genes, including Ance. Evidence for potential Ance involvement in the CI mechanism is described, including the prior report of Ance in spermatid differentiation, Wolbachia-induced sex-specific effects on Ance expression and an Ance mutation effect on CI levels. The results support the use of Wolbachia infected cell cultures as an appropriate model for predicting in vivo host/Wolbachia interactions. PMID:18171476

Variation in Thermal Sensitivity and Thermal Tolerances in an Invasive Species across a Climatic Gradient: Lessons from the Land Snail Cornu aspersum

PubMed Central

Gaitán-Espitia, Juan Diego; Belén Arias, María; Lardies, Marco A.; Nespolo, Roberto F.

2013-01-01

The ability of organisms to perform at different temperatures could be described by a continuous nonlinear reaction norm (i.e., thermal performance curve, TPC), in which the phenotypic trait value varies as a function of temperature. Almost any shift in the parameters of this performance curve could highlight the direct effect of temperature on organism fitness, providing a powerful framework for testing thermal adaptation hypotheses. Inter-and intraspecific differences in this performance curve are also reflected in thermal tolerances limits (e.g., critical and lethal limits), influencing the biogeographic patterns of species’ distribution. Within this context, here we investigated the intraspecific variation in thermal sensitivities and thermal tolerances in three populations of the invasive snail Cornu aspersum across a geographical gradient, characterized by different climatic conditions. Thus, we examined population differentiation in the TPCs, thermal-coma recovery times, expression of heat-shock proteins and standard metabolic rate (i.e., energetic costs of physiological differentiation). We tested two competing hypotheses regarding thermal adaptation (the “hotter is better” and the generalist-specialist trade-offs). Our results show that the differences in thermal sensitivity among populations of C. aspersum follow a latitudinal pattern, which is likely the result of a combination of thermodynamic constraints (“hotter is better”) and thermal adaptations to their local environments (generalist-specialist trade-offs). This finding is also consistent with some thermal tolerance indices such as the Heat-Shock Protein Response and the recovery time from chill-coma. However, mixed responses in the evaluated traits suggest that thermal adaptation in this species is not complete, as we were not able to detect any differences in neither energetic costs of physiological differentiation among populations, nor in the heat-coma recovery. PMID:23940617

Variation in thermal sensitivity and thermal tolerances in an invasive species across a climatic gradient: lessons from the land snail Cornu aspersum.

PubMed

Gaitán-Espitia, Juan Diego; Belén Arias, María; Lardies, Marco A; Nespolo, Roberto F

2013-01-01

The ability of organisms to perform at different temperatures could be described by a continuous nonlinear reaction norm (i.e., thermal performance curve, TPC), in which the phenotypic trait value varies as a function of temperature. Almost any shift in the parameters of this performance curve could highlight the direct effect of temperature on organism fitness, providing a powerful framework for testing thermal adaptation hypotheses. Inter-and intraspecific differences in this performance curve are also reflected in thermal tolerances limits (e.g., critical and lethal limits), influencing the biogeographic patterns of species' distribution. Within this context, here we investigated the intraspecific variation in thermal sensitivities and thermal tolerances in three populations of the invasive snail Cornu aspersum across a geographical gradient, characterized by different climatic conditions. Thus, we examined population differentiation in the TPCs, thermal-coma recovery times, expression of heat-shock proteins and standard metabolic rate (i.e., energetic costs of physiological differentiation). We tested two competing hypotheses regarding thermal adaptation (the "hotter is better" and the generalist-specialist trade-offs). Our results show that the differences in thermal sensitivity among populations of C. aspersum follow a latitudinal pattern, which is likely the result of a combination of thermodynamic constraints ("hotter is better") and thermal adaptations to their local environments (generalist-specialist trade-offs). This finding is also consistent with some thermal tolerance indices such as the Heat-Shock Protein Response and the recovery time from chill-coma. However, mixed responses in the evaluated traits suggest that thermal adaptation in this species is not complete, as we were not able to detect any differences in neither energetic costs of physiological differentiation among populations, nor in the heat-coma recovery.

Epigenetic Control of Cytokine Gene Expression: Regulation of the TNF/LT Locus and T Helper Cell Differentiation

PubMed Central

Falvo, James V.; Jasenosky, Luke D.; Kruidenier, Laurens; Goldfeld, Anne E.

2014-01-01

Epigenetics encompasses transient and heritable modifications to DNA and nucleosomes in the native chromatin context. For example, enzymatic addition of chemical moieties to the N-terminal “tails” of histones, particularly acetylation and methylation of lysine residues in the histone tails of H3 and H4, plays a key role in regulation of gene transcription. The modified histones, which are physically associated with gene regulatory regions that typically occur within conserved noncoding sequences, play a functional role in active, poised, or repressed gene transcription. The “histone code” defined by these modifications, along with the chromatin-binding acetylases, deacetylases, methylases, demethylases, and other enzymes that direct modifications resulting in specific patterns of histone modification, shows considerable evolutionary conservation from yeast to humans. Direct modifications at the DNA level, such as cytosine methylation at CpG motifs that represses promoter activity, are another highly conserved epigenetic mechanism of gene regulation. Furthermore, epigenetic modifications at the nucleosome or DNA level can also be coupled with higher-order intra- or interchromosomal interactions that influence the location of regulatory elements and that can place them in an environment of specific nucleoprotein complexes associated with transcription. In the mammalian immune system, epigenetic gene regulation is a crucial mechanism for a range of physiological processes, including the innate host immune response to pathogens and T cell differentiation driven by specific patterns of cytokine gene expression. Here, we will review current findings regarding epigenetic regulation of cytokine genes important in innate and/or adaptive immune responses, with a special focus upon the tumor necrosis factor/lymphotoxin locus and cytokine-driven CD4+ T cell differentiation into the Th1, Th2, and Th17 lineages. PMID:23683942

Comparison of Spontaneously Elicited Language Patterns in Specific Language Impairment and High-Functioning Autism.

PubMed

Craig, Megan; Trauner, Doris

2018-02-01

We aimed to characterize differences in the use of language in children with specific language impairment and high-functioning autism by analyzing verbal responses on standardized tests. The overall goal was to provide clinicians with additional tools with which to aid in distinguishing the two neurodevelopmental disorders. This study included 16 children with specific language impairment, 28 children with high-functioning autism, and 52 typically developing participants between the ages of six and 14. Groups were matched for age, and specific language impairment and high-functioning autism groups were matched on verbal and performance IQ. Responses from standardized tests were examined for response length, grammatical errors, filler words, perseverations, revisions (repeated attempts to begin or continue a sentence), off-topic attention shifts (lapses in attention to the task), and rambling. Data were analyzed using parametric and nonparametric methods. Specific language impairment responses were longer and contained more filler words than did those of the other two groups, whereas high-functioning autism responses exhibited more grammatical errors, off-topic attention shifts, and rambling. Specific language impairment and high-functioning autism responses showed higher rates of perseveration compared with controls. There were no significant differences in revisions among the three groups. Differences in language patterns of participants with specific language impairment and high-functioning autism may be useful to the clinician in helping to differentiate isolated language impairment from high-functioning autism. The results also support the conclusion that the two conditions are separable, and each exhibits a different pattern of language dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative phylogeography of co-distributed Phrygilus species (Aves, Thraupidae) from the Central Andes.

PubMed

Álvarez-Varas, R; González-Acuña, D; Vianna, J A

2015-09-01

The Neotropical ecoregion has been an important place of avian diversification where dispersal and allopatric events coupled with periods of active orogeny and climate change (Late Pliocene-Pleistocene) have shaped the biogeography of the region. In the Neotropics, avian population structure has been sculpted not only by geographical barriers, but also by non-allopatric factors such as natural selection and local adaptation. We analyzed the genetic variation of six co-distributed Phrygilus species from the Central Andes, based on mitochondrial and nuclear markers in conjunction with morphological differentiation. We examined if Phrygilus species share patterns of population structure and historical demography, and reviewed the intraspecific taxonomy in part of their geographic range. Our results showed different phylogeographic patterns between species, even among those belonging to the same phylogenetic clade. P. alaudinus, P. atriceps, and P. unicolor showed genetic differentiation mediated by allopatric mechanisms in response to specific geographic barriers; P. gayi showed sympatric lineages in northern Chile, while P. plebejus and P. fruticeti showed a single genetic group. We found no relationship between geographic range size and genetic structure. Additionally, a signature of expansion was found in three species related to the expansion of paleolakes in the Altiplano region and the drying phase of the Atacama Desert. Morphological analysis showed congruence with molecular data and intraspecific taxonomy in most species. While we detected genetic and phenotypic patterns that could be related to natural selection and local adaptation, our results indicate that allopatric events acted as a major factor in the population differentiation of Phrygilus species. Copyright © 2015 Elsevier Inc. All rights reserved.

Transcriptome analysis of the painted lady butterfly, Vanessa cardui during wing color pattern development.

PubMed

Connahs, Heidi; Rhen, Turk; Simmons, Rebecca B

2016-03-31

Butterfly wing color patterns are an important model system for understanding the evolution and development of morphological diversity and animal pigmentation. Wing color patterns develop from a complex network composed of highly conserved patterning genes and pigmentation pathways. Patterning genes are involved in regulating pigment synthesis however the temporal expression dynamics of these interacting networks is poorly understood. Here, we employ next generation sequencing to examine expression patterns of the gene network underlying wing development in the nymphalid butterfly, Vanessa cardui. We identified 9, 376 differentially expressed transcripts during wing color pattern development, including genes involved in patterning, pigmentation and gene regulation. Differential expression of these genes was highest at the pre-ommochrome stage compared to early pupal and late melanin stages. Overall, an increasing number of genes were down-regulated during the progression of wing development. We observed dynamic expression patterns of a large number of pigment genes from the ommochrome, melanin and also pteridine pathways, including contrasting patterns of expression for paralogs of the yellow gene family. Surprisingly, many patterning genes previously associated with butterfly pattern elements were not significantly up-regulated at any time during pupation, although many other transcription factors were differentially expressed. Several genes involved in Notch signaling were significantly up-regulated during the pre-ommochrome stage including slow border cells, bunched and pebbles; the function of these genes in the development of butterfly wings is currently unknown. Many genes involved in ecdysone signaling were also significantly up-regulated during early pupal and late melanin stages and exhibited opposing patterns of expression relative to the ecdysone receptor. Finally, a comparison across four butterfly transcriptomes revealed 28 transcripts common to all four species that have no known homologs in other metazoans. This study provides a comprehensive list of differentially expressed transcripts during wing development, revealing potential candidate genes that may be involved in regulating butterfly wing patterns. Some differentially expressed genes have no known homologs possibly representing genes unique to butterflies. Results from this study also indicate that development of nymphalid wing patterns may arise not only from melanin and ommochrome pigments but also the pteridine pigment pathway.

An Integrated Analysis of MicroRNA and mRNA Expression Profiles to Identify RNA Expression Signatures in Lambskin Hair Follicles in Hu Sheep

PubMed Central

Lv, Xiaoyang; Sun, Wei; Yin, Jinfeng; Ni, Rong; Su, Rui; Wang, Qingzeng; Gao, Wen; Bao, Jianjun; Yu, Jiarui; Wang, Lihong; Chen, Ling

2016-01-01

Wave patterns in lambskin hair follicles are an important factor determining the quality of sheep’s wool. Hair follicles in lambskin from Hu sheep, a breed unique to China, have 3 types of waves, designated as large, medium, and small. The quality of wool from small wave follicles is excellent, while the quality of large waves is considered poor. Because no molecular and biological studies on hair follicles of these sheep have been conducted to date, the molecular mechanisms underlying the formation of different wave patterns is currently unknown. The aim of this article was to screen the candidate microRNAs (miRNA) and genes for the development of hair follicles in Hu sheep. Two-day-old Hu lambs were selected from full-sib individuals that showed large, medium, and small waves. Integrated analysis of microRNA and mRNA expression profiles employed high-throughout sequencing technology. Approximately 13, 24, and 18 differentially expressed miRNAs were found between small and large waves, small and medium waves, and medium and large waves, respectively. A total of 54, 190, and 81 differentially expressed genes were found between small and large waves, small and medium waves, and medium and large waves, respectively, by RNA sequencing (RNA-seq) analysis. Differentially expressed genes were classified using gene ontology and pathway analyses. They were found to be mainly involved in cell differentiation, proliferation, apoptosis, growth, immune response, and ion transport, and were associated with MAPK and the Notch signaling pathway. Reverse transcription-polymerase chain reaction (RT-PCR) analyses of differentially-expressed miRNA and genes were consistent with sequencing results. Integrated analysis of miRNA and mRNA expression indicated that, compared to small waves, large waves included 4 downregulated miRNAs that had regulatory effects on 8 upregulated genes and 3 upregulated miRNAs, which in turn influenced 13 downregulated genes. Compared to small waves, medium waves included 13 downregulated miRNAs that had regulatory effects on 64 upregulated genes and 4 upregulated miRNAs, which in turn had regulatory effects on 22 downregulated genes. Compared to medium waves, large waves consisted of 13 upregulated miRNAs that had regulatory effects on 48 downregulated genes. These differentially expressed miRNAs and genes may play a significant role in forming different patterns, and provide evidence for the molecular mechanisms underlying the formation of hair follicles of varying patterns. PMID:27404636

Evaluation of a toxicogenomic approach to the local lymph node assay (LLNA).

PubMed

Boverhof, Darrell R; Gollapudi, B Bhaskar; Hotchkiss, Jon A; Osterloh-Quiroz, Mandy; Woolhiser, Michael R

2009-02-01

Genomic technologies have the potential to enhance and complement existing toxicology endpoints; however, assessment of these approaches requires a systematic evaluation including a robust experimental design with genomic endpoints anchored to traditional toxicology endpoints. The present study was conducted to assess the sensitivity of genomic responses when compared with the traditional local lymph node assay (LLNA) endpoint of lymph node cell proliferation and to evaluate the responses for their ability to provide insights into mode of action. Female BALB/c mice were treated with the sensitizer trimellitic anhydride (TMA), following the standard LLNA dosing regimen, at doses of 0.1, 1, or 10% and traditional tritiated thymidine ((3)HTdR) incorporation and gene expression responses were monitored in the auricular lymph nodes. Additional mice dosed with either vehicle or 10% TMA and sacrificed on day 4 or 10, were also included to examine temporal effects on gene expression. Analysis of (3)HTdR incorporation revealed TMA-induced stimulation indices of 2.8, 22.9, and 61.0 relative to vehicle with an EC(3) of 0.11%. Examination of the dose-response gene expression responses identified 9, 833, and 2122 differentially expressed genes relative to vehicle for the 0.1, 1, and 10% TMA dose groups, respectively. Calculation of EC(3) values for differentially expressed genes did not identify a response that was more sensitive than the (3)HTdR value, although a number of genes displayed comparable sensitivity. Examination of temporal responses revealed 1760, 1870, and 953 differentially expressed genes at the 4-, 6-, and 10-day time points respectively. Functional analysis revealed many responses displayed dose- and time-specific induction patterns within the functional categories of cellular proliferation and immune response, including numerous immunoglobin genes which were highly induced at the day 10 time point. Overall, these experiments have systematically illustrated the potential utility of genomic endpoints to enhance the LLNA and support further exploration of this approach through examination of a more diverse array of chemicals.

Identification and handling of artifactual gene expression profiles emerging in microarray hybridization experiments

PubMed Central

Brodsky, Leonid; Leontovich, Andrei; Shtutman, Michael; Feinstein, Elena

2004-01-01

Mathematical methods of analysis of microarray hybridizations deal with gene expression profiles as elementary units. However, some of these profiles do not reflect a biologically relevant transcriptional response, but rather stem from technical artifacts. Here, we describe two technically independent but rationally interconnected methods for identification of such artifactual profiles. Our diagnostics are based on detection of deviations from uniformity, which is assumed as the main underlying principle of microarray design. Method 1 is based on detection of non-uniformity of microarray distribution of printed genes that are clustered based on the similarity of their expression profiles. Method 2 is based on evaluation of the presence of gene-specific microarray spots within the slides’ areas characterized by an abnormal concentration of low/high differential expression values, which we define as ‘patterns of differentials’. Applying two novel algorithms, for nested clustering (method 1) and for pattern detection (method 2), we can make a dual estimation of the profile’s quality for almost every printed gene. Genes with artifactual profiles detected by method 1 may then be removed from further analysis. Suspicious differential expression values detected by method 2 may be either removed or weighted according to the probabilities of patterns that cover them, thus diminishing their input in any further data analysis. PMID:14999086

ETOILE Regulates Developmental Patterning in the Filamentous Brown Alga Ectocarpus siliculosus[W

PubMed Central

Le Bail, Aude; Billoud, Bernard; Le Panse, Sophie; Chenivesse, Sabine; Charrier, Bénédicte

2011-01-01

Brown algae are multicellular marine organisms evolutionarily distant from both metazoans and land plants. The molecular or cellular mechanisms that govern the developmental patterning in brown algae are poorly characterized. Here, we report the first morphogenetic mutant, étoile (etl), produced in the brown algal model Ectocarpus siliculosus. Genetic, cellular, and morphometric analyses showed that a single recessive locus, ETL, regulates cell differentiation: etl cells display thickening of the extracellular matrix (ECM), and the elongated, apical, and actively dividing E cells are underrepresented. As a result of this defect, the overrepresentation of round, branch-initiating R cells in the etl mutant leads to the rapid induction of the branching process at the expense of the uniaxial growth in the primary filament. Computational modeling allowed the simulation of the etl mutant phenotype by including a modified response to the neighborhood information in the division rules used to specify wild-type development. Microarray experiments supported the hypothesis of a defect in cell–cell communication, as primarily Lin-Notch-domain transmembrane proteins, which share similarities with metazoan Notch proteins involved in binary cell differentiation were repressed in etl. Thus, our study highlights the role of the ECM and of novel transmembrane proteins in cell–cell communication during the establishment of the developmental pattern in this brown alga. PMID:21478443

Traumatic Life Events and Psychopathology in a High Risk, Ethnically Diverse Sample of Young Children: A Person-Centered Approach.

PubMed

Hagan, Melissa J; Sulik, Michael J; Lieberman, Alicia F

2016-07-01

Studies of the association between traumatic experiences and psychopathology in early childhood have primarily focused on specific types of events (e.g., sexual abuse) or aggregated different types of events without differentiating among them. We extend this body of work by investigating patterns of traumatic event exposure in a high-risk, ethnically diverse sample of children ages 3-6 (N = 211; 51 % female) and relating these different patterns to parents' reports of child externalizing, internalizing, and post-traumatic stress symptomatology. Using latent class analysis, which divides a heterogeneous population into homogenous subpopulations, we identified three patterns of traumatic events based on parents' responses to an interview-based assessment of trauma exposure in young children: (1) severe exposure, characterized by a combination of family violence and victimization; (2) witnessing family violence without victimization; and (3) moderate exposure, characterized by an absence of family violence but a moderate probability of other events. The severe exposure class exhibited elevated internalizing and post-traumatic stress symptoms relative to the witness to violence and moderate exposure classes, controlling for average number of traumatic events. Results highlight the need for differentiation between profiles of traumatic life event exposure and the potential for person-centered methods to complement the cumulative risk perspective.

Intraspecific variation in the use of water sources by the circum-Mediterranean conifer Pinus halepensis.

PubMed

Voltas, Jordi; Lucabaugh, Devon; Chambel, Maria Regina; Ferrio, Juan Pedro

2015-12-01

The relevance of interspecific variation in the use of plant water sources has been recognized in drought-prone environments. By contrast, the characterization of intraspecific differences in water uptake patterns remains elusive, although preferential access to particular soil layers may be an important adaptive response for species along aridity gradients. Stable water isotopes were analysed in soil and xylem samples of 56 populations of the drought-avoidant conifer Pinus halepensis grown in a common garden test. We found that most populations reverted to deep soil layers as the main plant water source during seasonal summer droughts. More specifically, we detected a clear geographical differentiation among populations in water uptake patterns even under relatively mild drought conditions (early autumn), with populations originating from more arid regions taking up more water from deep soil layers. However, the preferential access to deep soil water was largely independent of aboveground growth. Our findings highlight the high plasticity and adaptive relevance of the differential access to soil water pools among Aleppo pine populations. The observed ecotypic patterns point to the adaptive relevance of resource investment in deep roots as a strategy towards securing a source of water in dry environments for P. halepensis. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Nuclear microsatellites reveal contrasting patterns of genetic structure between western and southeastern European populations of the common ash (Fraxinus excelsior L.).

PubMed

Heuertz, Myriam; Hausman, Jean-François; Hardy, Olivier J; Vendramin, Giovanni G; Frascaria-Lacoste, Nathalie; Vekemans, Xavier

2004-05-01

To determine extant patterns of population genetic structure in common ash and gain insight into postglacial recolonization processes, we applied multilocus-based Bayesian approaches to data from 36 European populations genotyped at five nuclear microsatellite loci. We identified two contrasting patterns in terms of population genetic structure: (1) a large area from the British Isles to Lithuania throughout central Europe constituted effectively a single deme, whereas (2) strong genetic differentiation occurred over short distances in Sweden and southeastern Europe. Concomitant geographical variation was observed in estimates of allelic richness and genetic diversity, which were lowest in populations from southeastern Europe, that is, in regions close to putative ice age refuges, but high in western and central Europe, that is, in more recently recolonized areas. We suggest that in southeastern Europe, restricted postglacial gene flow caused by a rapid expansion of refuge populations in a mountainous topography is responsible for the observed strong genetic structure. In contrast, admixture of previously differentiated gene pools and high gene flow at the onset of postglacial recolonization of western and central Europe would have homogenized the genetic structure and raised the levels of genetic diversity above values in the refuges.

Plasticity of DNA methylation and gene expression under zinc deficiency in Arabidopsis roots.

PubMed

Chen, Xiaochao; Schönberger, Brigitte; Menz, Jochen; Ludewig, Uwe

2018-05-25

DNA methylation is a heritable chromatin modification that maintains chromosome stability, regulates transposon silencing and appears to be involved in gene expression in response to environmental conditions. Environmental stress alters DNA methylation patterns that are correlated with gene expression differences. Here, genome-wide differential DNA-methylation was identified upon prolonged Zn deficiency, leading to hypo- and hyper-methylated chromosomal regions. Preferential CpG methylation changes occurred in gene promoters and gene bodies, but did not overlap with transcriptional start sites. Methylation changes were also prominent in transposable elements. By contrast, non-CG methylation differences were exclusively found in promoters of protein coding genes and in transposable elements. Strongly Zn deficiency-induced genes and their promoters were mostly non-methylated, irrespective of Zn supply. Differential DNA methylation in the CpG and CHG, but not in the CHH context, was found close to a few up-regulated Zn-deficiency genes. However, the transcriptional Zn-deficiency response in roots appeared little correlated with associated DNA methylation changes in promoters or gene bodies. Furthermore, under Zn deficiency, developmental defects were identified in an Arabidopsis mutant lacking non-CpG methylation. The root methylome thus responds specifically to a micro-nutrient deficiency and is important for efficient Zn utilization at low availability, but the relationship of differential methylation and differentially expressed genes is surprisingly poor.

Differentiation of hopelessness, helplessness, and powerlessness using Erik Erikson's "Roots of virtue".

PubMed

Drew, B L

1990-10-01

Hopelessness, helplessness, and powerlessness have been identified as phenomena of concern to psychiatric nursing practice by an American Nurses' Association (ANA) task force. These concepts, however, have not been clearly distinguished from each other. The resulting lack of clarity decreases the usefulness of nursing diagnoses in directing strategies for intervention. The purpose of this article is to differentiate the phenomena of hopelessness, helplessness, and powerlessness using Erik Erikson's "Roots of virtue" as a conceptual framework. The relationship between the frustration of early childhood tasks and later adult response patterns is discussed. Clinical examples illustrate that knowledge of childhood issues guides the formulation of therapeutic goals and interventions to address the experience of hopelessness, helplessness, and powerlessness.

Test Response Patterns which Differentiate between Two Levels of Behavior of Mentally Retarded Children. Final Report.

ERIC Educational Resources Information Center

Boswell, James D.

The interrelations between mental age (MA), IQ, and mediation were studied in 72 retardates in special classes. Subjects were selected to fall into sexually balanced groups of six in 12 MA-IQ categories (IQ 50-59, 60-69, 70-79, and 80-89; MA 4-0 to 5-11, 6-0 to 7-11, and 8-0 to 9-11). The apparatus alternately displayed two pairs of stimuli, and…

Differential gene expression patterns during embryonic development of sea urchin exposed to triclosan.

PubMed

Hwang, Jinik; Suh, Sung-Suk; Park, Mirye; Park, So Yun; Lee, Sukchan; Lee, Taek-Kyun

2017-02-01

Triclosan (TCS; 2,4,4'-trichloro-2'-hydroxydiphenyl ether) is a broad-spectrum antibacterial agent used in common industrial, personal care and household products which are eventually rinsed down the drain and discharged with wastewater effluent. It is therefore commonly found in the aquatic environment, leading to the continual exposure of aquatic organisms to TCS and the accumulation of the antimicrobial and its harmful degradation products in their bodies. Toxic effects of TCS on reproductive and developmental progression of some aquatic organisms have been suggested but the underlying molecular mechanisms have not been defined. We investigated the expression patterns of genes involved in the early development of TCS-treated sea urchin Strongylocentrotus nudus using cDNA microarrays. We observed that the predominant consequence of TCS treatment in this model system was the widespread repression of TCS-modulated genes. In particular, empty spiracles homeobox 1 (EMX-1), bone morphogenic protein, and chromosomal binding protein genes showed a significant decrease in expression in response to TCS. These results suggest that TCS can induce abnormal development of sea urchin embryos through the concomitant suppression of a number of genes that are necessary for embryonic differentiation in the blastula stage. Our data provide new insight into the crucial role of genes associated with embryonic development in response to TCS. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 426-433, 2017. © 2016 Wiley Periodicals, Inc.

C2H2 type of zinc finger transcription factors in foxtail millet define response to abiotic stresses.

PubMed

Muthamilarasan, Mehanathan; Bonthala, Venkata Suresh; Mishra, Awdhesh Kumar; Khandelwal, Rohit; Khan, Yusuf; Roy, Riti; Prasad, Manoj

2014-09-01

C2H2 type of zinc finger transcription factors (TFs) play crucial roles in plant stress response and hormone signal transduction. Hence considering its importance, genome-wide investigation and characterization of C2H2 zinc finger proteins were performed in Arabidopsis, rice and poplar but no such study was conducted in foxtail millet which is a C4 Panicoid model crop well known for its abiotic stress tolerance. The present study identified 124 C2H2-type zinc finger TFs in foxtail millet (SiC2H2) and physically mapped them onto the genome. The gene duplication analysis revealed that SiC2H2s primarily expanded in the genome through tandem duplication. The phylogenetic tree classified these TFs into five groups (I-V). Further, miRNAs targeting SiC2H2 transcripts in foxtail millet were identified. Heat map demonstrated differential and tissue-specific expression patterns of these SiC2H2 genes. Comparative physical mapping between foxtail millet SiC2H2 genes and its orthologs of sorghum, maize and rice revealed the evolutionary relationships of C2H2 type of zinc finger TFs. The duplication and divergence data provided novel insight into the evolutionary aspects of these TFs in foxtail millet and related grass species. Expression profiling of candidate SiC2H2 genes in response to salinity, dehydration and cold stress showed differential expression pattern of these genes at different time points of stresses.

Pigment cell interactions and differential xanthophore recruitment underlying zebrafish stripe reiteration and Danio pattern evolution

PubMed Central

Patterson, Larissa B.; Bain, Emily J.; Parichy, David M.

2014-01-01

Fishes have diverse pigment patterns, yet mechanisms of pattern evolution remain poorly understood. In zebrafish, Danio rerio, pigment-cell autonomous interactions generate dark stripes of melanophores that alternate with light interstripes of xanthophores and iridophores. Here, we identify mechanisms underlying the evolution of a uniform pattern in D. albolineatus in which all three pigment cell classes are intermingled. We show that in this species xanthophores differentiate precociously over a wider area, and that cis regulatory evolution has increased expression of xanthogenic Colony Stimulating Factor-1 (Csf1). Expressing Csf1 similarly in D. rerio has cascading effects, driving the intermingling of all three pigment cell classes and resulting in the loss of stripes, as in D. albolineatus. Our results identify novel mechanisms of pattern development and illustrate how pattern diversity can be generated when a core network of pigment-cell autonomous interactions is coupled with changes in pigment cell differentiation. PMID:25374113

Comparison of response patterns in different survey designs: a longitudinal panel with mixed-mode and online-only design.

PubMed

Rübsamen, Nicole; Akmatov, Manas K; Castell, Stefanie; Karch, André; Mikolajczyk, Rafael T

2017-01-01

Increasing availability of the Internet allows using only online data collection for more epidemiological studies. We compare response patterns in a population-based health survey using two survey designs: mixed-mode (choice between paper-and-pencil and online questionnaires) and online-only design (without choice). We used data from a longitudinal panel, the Hygiene and Behaviour Infectious Diseases Study (HaBIDS), conducted in 2014/2015 in four regions in Lower Saxony, Germany. Individuals were recruited using address-based probability sampling. In two regions, individuals could choose between paper-and-pencil and online questionnaires. In the other two regions, individuals were offered online-only participation. We compared sociodemographic characteristics of respondents who filled in all panel questionnaires between the mixed-mode group (n = 1110) and the online-only group (n = 482). Using 134 items, we performed multinomial logistic regression to compare responses between survey designs in terms of type (missing, "do not know" or valid response) and ordinal regression to compare responses in terms of content. We applied the false discovery rates (FDR) to control for multiple testing and investigated effects of adjusting for sociodemographic characteristic. For validation of the differential response patterns between mixed-mode and online-only, we compared the response patterns between paper and online mode among the respondents in the mixed-mode group in one region (n = 786). Respondents in the online-only group were older than those in the mixed-mode group, but both groups did not differ regarding sex or education. Type of response did not differ between the online-only and the mixed-mode group. Survey design was associated with different content of response in 18 of the 134 investigated items; which decreased to 11 after adjusting for sociodemographic variables. In the validation within the mixed-mode, only two of those were among the 11 significantly different items. The probability of observing by chance the same two or more significant differences in this setting was 22%. We found similar response patterns in both survey designs with only few items being answered differently, likely attributable to chance. Our study supports the equivalence of the compared survey designs and suggests that, in the studied setting, using online-only design does not cause strong distortion of the results.

Response of the elderly to disaster: an age-stratified analysis.

PubMed

Bolin, R; Klenow, D J

This article analyzes the effects of chronological age of disaster victims on their responses to stress effects of natural disasters. Previous research is reviewed and major findings of that research are noted. Findings regarding disaster losses, physical impacts, aid utilization patterns, kinship relations, relative deprivation, social-psychological impacts, neglect of elderly disaster victims, and differential recovery rates by age are retested on new data. Data described herein were gathered using survey techniques in two disaster stricken communities in Texas. Elderly victims' responses to the tornadoes are compared to a nonelderly (under sixty years of age) group to assess differences. Findings of previous research were, in many instances, supported although certain divergences between the current findings and preceding findings are noted, particularly in rates of recovery.

Allele-specific expression in the human heart and its application to postoperative atrial fibrillation and myocardial ischemia.

PubMed

Sigurdsson, Martin I; Saddic, Louis; Heydarpour, Mahyar; Chang, Tzuu-Wang; Shekar, Prem; Aranki, Sary; Couper, Gregory S; Shernan, Stanton K; Seidman, Jon G; Body, Simon C; Muehlschlegel, Jochen D

2016-12-06

Allele-specific expression (ASE) is differential expression of each of the two chromosomal alleles of an autosomal gene. We assessed ASE patterns in the human left atrium (LA, n = 62) and paired samples from the left ventricle (LV, n = 76) before and after ischemia, and tested the utility of differential ASE to identify genes associated with postoperative atrial fibrillation (poAF) and myocardial ischemia. Following genotyping from whole blood and whole-genome sequencing of LA and LV samples, we called ASE using sequences overlapping heterozygous SNPs using rigorous quality control to minimize false ASE calling. ASE patterns were compared between cardiac chambers and with a validation cohort from cadaveric tissue. ASE patterns in the LA were compared between patients who had poAF and those who did not. Changes in ASE in the LV were compared between paired baseline and post-ischemia samples. ASE was found for 3404 (5.1%) and 8642 (4.0%) of SNPs analyzed in the LA and LV, respectively. Out of 6157 SNPs with ASE analyzed in both chambers, 2078 had evidence of ASE in both LA and LV (p < 0.0001). The SNP with the greatest ASE difference in the LA of patients with and without postoperative atrial fibrillation was within the gelsolin (GSN) gene, previously associated with atrial fibrillation in mice. The genes with differential ASE in poAF were enriched for myocardial structure genes, indicating the importance of atrial remodeling in the pathophysiology of AF. The greatest change in ASE between paired post-ischemic and baseline samples of the LV was in the zinc finger and homeodomain protein 2 (ZHX2) gene, a modulator of plasma lipids. Genes with differential ASE in ischemia were enriched in the ubiquitin ligase complex pathway associated with the ischemia-reperfusion response. Our results establish a pattern of ASE in the human heart, with a high degree of shared ASE between cardiac chambers as well as chamber-specific ASE. Furthermore, ASE analysis can be used to identify novel genes associated with (poAF) and myocardial ischemia.

Human NOD2 Recognizes Structurally Unique Muramyl Dipeptides from Mycobacterium leprae

PubMed Central

Schenk, Mirjam; Mahapatra, Sebabrata; Le, Phuonganh; Kim, Hee Jin; Choi, Aaron W.; Brennan, Patrick J.; Belisle, John T.

2016-01-01

The innate immune system recognizes microbial pathogens via pattern recognition receptors. One such receptor, NOD2, via recognition of muramyl dipeptide (MDP), triggers a distinct network of innate immune responses, including the production of interleukin-32 (IL-32), which leads to the differentiation of monocytes into dendritic cells (DC). NOD2 has been implicated in the pathogenesis of human leprosy, yet it is not clear whether Mycobacterium leprae, which has a distinct MDP structure, can activate this pathway. We investigated the effect of MDP structure on the innate immune response, finding that infection of monocytes with M. leprae induces IL-32 and DC differentiation in a NOD2-dependent manner. The presence of the proximal l-Ala instead of Gly in the common configuration of the peptide side chain of M. leprae did not affect recognition by NOD2 or cytokine production. Furthermore, amidation of the d-Glu residue did not alter NOD2 activation. These data provide experimental evidence that NOD2 recognizes naturally occurring structural variants of MDP. PMID:27297389

Item response theory detects differential item functioning between healthy and ill children in QoL measures

PubMed Central

Langer, Michelle M.; Hill, Cheryl D.; Thissen, David; Burwinkle, Tasha M.; Varni, James W.; DeWalt, Darren A.

2008-01-01

Objective To demonstrate the value of item response theory (IRT) and differential item functioning (DIF) methods in examining a health-related quality of life (HRQOL) measure in children and adolescents. Study Design and Setting This illustration uses data from 5,429 children using the four subscales of the PedsQL™ 4.0 Generic Core Scales. The IRT model-based likelihood ratio test was used to detect and evaluate DIF between healthy children and children with a chronic condition. Results DIF was detected for a majority of items but cancelled out at the total test score level due to opposing directions of DIF. Post-hoc analysis indicated that this pattern of results may be due to multidimensionality. We discuss issues in detecting and handling DIF. Conclusion This paper describes how to perform DIF analyses in validating a questionnaire to ensure that scores have equivalent meaning across subgroups. It offers insight into ways information gained through the analysis can be used to evaluate an existing scale. PMID:18226750

MAINTENANCE OF ECOLOGICALLY SIGNIFICANT GENETIC VARIATION IN THE TIGER SWALLOWTAIL BUTTERFLY THROUGH DIFFERENTIAL SELECTION AND GENE FLOW.

PubMed

Bossart, J L; Scriber, J M

1995-12-01

Differential selection in a heterogeneous environment is thought to promote the maintenance of ecologically significant genetic variation. Variation is maintained when selection is counterbalanced by the homogenizing effects of gene flow and random mating. In this study, we examine the relative importance of differential selection and gene flow in maintaining genetic variation in Papilio glaucus. Differential selection on traits contributing to successful use of host plants (oviposition preference and larval performance) was assessed by comparing the responses of southern Ohio, north central Georgia, and southern Florida populations of P. glaucus to three hosts: Liriodendron tulipifera, Magnolia virginiana, and Prunus serotina. Gene flow among populations was estimated using allozyme frequencies from nine polymorphic loci. Significant genetic differentiation was observed among populations for both oviposition preference and larval performance. This differentiation was interpreted to be the result of selection acting on Florida P. glaucus for enhanced use of Magnolia, the prevalent host in Florida. In contrast, no evidence of population differentiation was revealed by allozyme frequencies. F ST -values were very small and Nm, an estimate of the relative strengths of gene flow and genetic drift, was large, indicating that genetic exchange among P. glaucus populations is relatively unrestricted. The contrasting patterns of spatial differentiation for host-use traits and lack of differentiation for electrophoretically detectable variation implies that differential selection among populations will be counterbalanced by gene flow, thereby maintaining genetic variation for host-use traits. © 1995 The Society for the Study of Evolution.

FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathways.

PubMed

Devanna, Paolo; Middelbeek, Jeroen; Vernes, Sonja C

2014-01-01

FOXP2 was the first gene shown to cause a Mendelian form of speech and language disorder. Although developmentally expressed in many organs, loss of a single copy of FOXP2 leads to a phenotype that is largely restricted to orofacial impairment during articulation and linguistic processing deficits. Why perturbed FOXP2 function affects specific aspects of the developing brain remains elusive. We investigated the role of FOXP2 in neuronal differentiation and found that FOXP2 drives molecular changes consistent with neuronal differentiation in a human model system. We identified a network of FOXP2 regulated genes related to retinoic acid signaling and neuronal differentiation. FOXP2 also produced phenotypic changes associated with neuronal differentiation including increased neurite outgrowth and reduced migration. Crucially, cells expressing FOXP2 displayed increased sensitivity to retinoic acid exposure. This suggests a mechanism by which FOXP2 may be able to increase the cellular differentiation response to environmental retinoic acid cues for specific subsets of neurons in the brain. These data demonstrate that FOXP2 promotes neuronal differentiation by interacting with the retinoic acid signaling pathway and regulates key processes required for normal circuit formation such as neuronal migration and neurite outgrowth. In this way, FOXP2, which is found only in specific subpopulations of neurons in the brain, may drive precise neuronal differentiation patterns and/or control localization and connectivity of these FOXP2 positive cells.

FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathways

PubMed Central

Devanna, Paolo; Middelbeek, Jeroen; Vernes, Sonja C.

2014-01-01

FOXP2 was the first gene shown to cause a Mendelian form of speech and language disorder. Although developmentally expressed in many organs, loss of a single copy of FOXP2 leads to a phenotype that is largely restricted to orofacial impairment during articulation and linguistic processing deficits. Why perturbed FOXP2 function affects specific aspects of the developing brain remains elusive. We investigated the role of FOXP2 in neuronal differentiation and found that FOXP2 drives molecular changes consistent with neuronal differentiation in a human model system. We identified a network of FOXP2 regulated genes related to retinoic acid signaling and neuronal differentiation. FOXP2 also produced phenotypic changes associated with neuronal differentiation including increased neurite outgrowth and reduced migration. Crucially, cells expressing FOXP2 displayed increased sensitivity to retinoic acid exposure. This suggests a mechanism by which FOXP2 may be able to increase the cellular differentiation response to environmental retinoic acid cues for specific subsets of neurons in the brain. These data demonstrate that FOXP2 promotes neuronal differentiation by interacting with the retinoic acid signaling pathway and regulates key processes required for normal circuit formation such as neuronal migration and neurite outgrowth. In this way, FOXP2, which is found only in specific subpopulations of neurons in the brain, may drive precise neuronal differentiation patterns and/or control localization and connectivity of these FOXP2 positive cells. PMID:25309332

Affect and Sexual Responsivity in Men with and without a History of Sexual Aggression

PubMed Central

Craig, Amber N.; Peterson, Zoë D.; Janssen, Erick; Goodrich, David; Heiman, Julia R.

2017-01-01

Despite increased attention to understanding risk factors for sexual aggression, knowledge regarding the emotional and sexual arousal patterns of sexually aggressive men remains limited. The current study examined whether sexually aggressive men exhibit unique profiles of affective responsivity, in particular to negatively-valenced stimuli, as well as sexual arousal patterns that differentiate them from nonaggressive men. We presented 78 young men (38 sexually aggressive and 40 nonaggressive) with a series of videos designed to induce positive, sad, or anxious affect. Affect and subjective sexual arousal were assessed following each film and erectile responses were measured continuously. Sexually aggressive men reported significantly higher levels of sexual arousal following both the positive and negative conditions as compared to nonaggressive men. Erectile responses of sexually aggressive men were significantly greater than nonaggressive men’s following the positive affect induction. Self-reported positive affect, but not negative affect, was a significant predictor of subjective sexual arousal for both groups of men. Compared to nonaggressive men, sexually aggressive men showed significantly weaker correlations between subjective and physiological sexual arousal. Findings suggest that generalized heightened propensity for sexual arousal may be a risk factor for sexually aggressive behavior. PMID:28388245

Seed storage conditions change the germination pattern of clonal growth plants in Mediterranean salt marshes

USGS Publications Warehouse

Espinar, J.L.; Garcia, L.V.; Clemente, L.

2005-01-01

The effect of salinity level and extended exposure to different salinity and flooding conditions on germination patterns of three saltmarsh clonal growth plants (Juncus subulatus, Scirpus litoralis, and S. maritimus) was studied. Seed exposure to extended flooding and saline conditions significantly affected the outcome of the germination process in a different, though predictable, way for each species, after favorable conditions for germination were restored. Tolerance of the germination process was related to the average salinity level measured during the growth/germination season at sites where established individuals of each species dominated the species cover. No relationship was found between salinity tolerance of the germination process and seed response to extended exposure to flooding and salinity conditions. The salinity response was significantly related to the conditions prevailing in the habitats of the respective species during the unfavorable (nongrowth/nongermination) season. Our results indicate that changes in salinity and hydrology while seeds are dormant affect the outcome of the seed-bank response, even when conditions at germination are identical. Because these environmental-history-dependent responses differentially affect seed germination, seedling density, and probably sexual recruitment in the studied and related species, these influences should be considered for wetland restoration and management.

Characterization of WRKY transcription factors in Solanum lycopersicum reveals collinearity and their expression patterns under cold treatment.

PubMed

Chen, Lin; Yang, Yang; Liu, Can; Zheng, Yanyan; Xu, Mingshuang; Wu, Na; Sheng, Jiping; Shen, Lin

2015-08-28

WRKY transcription factors play an important role in cold defense of plants. However, little information is available about the cold-responsive WRKYs in tomato (Solanum lycopersicum). In the present study, a complete characterization of this gene family was described. Eighty WRKY genes in the tomato genome were identified. Almost all WRKY genes contain putative stress-responsive cis-elements in their promoter regions. Segmental duplications contributed significantly to the expansion of the SlWRKY gene family. Transcriptional analysis revealed notable differential expression in tomato tissues and expression patterns under cold stress, which indicated wide functional divergence in this family. Ten WRKYs in tomato were strongly induced more than 2-fold during cold stress. These genes represented candidate genes for future functional analysis of WRKYs involved in the cold-related signal pathways. Our data provide valuable information about tomato WRKY proteins and form a foundation for future studies of these proteins, especially for those that play an important role in response to cold stress. Copyright © 2015 Elsevier Inc. All rights reserved.

Stimulation of contacts in ventral but not dorsal subthalamic nucleus normalizes response switching in Parkinson's disease

PubMed Central

Greenhouse, Ian; Gould, Sherrie; Houser, Melissa; Aron, Adam R.

2014-01-01

Switching between responses is a key executive function known to rely on the frontal cortex and the basal ganglia. Here we aimed to establish with greater anatomical specificity whether such switching could be mediated via different possible frontal–basal-ganglia circuits. Accordingly, we stimulated dorsal vs. ventral contacts of electrodes in the subthalamic nucleus (STN) in Parkinson's patients during switching performance, and also studied matched controls. The patients underwent three sessions: once with bilateral dorsal contact stimulation, once with bilateral ventral contact stimulation, and once Off stimulation. Patients Off stimulation showed abnormal patterns of switching, and stimulation of the ventral contacts but not the dorsal contacts normalized the pattern of behavior relative to controls. This provides some of the first evidence in humans that stimulation of dorsal vs. ventral STN DBS contacts has differential effects on executive function. As response switching is an executive function known to rely on prefrontal cortex, these results suggest that ventral contact stimulation affected an executive/associative cortico-basal ganglia circuit. PMID:23562963

Spatial scaling patterns and functional redundancies in a changing boreal lake landscape

USGS Publications Warehouse

Angeler, David G.; Allen, Craig R.; Uden, Daniel R.; Johnson, Richard K.

2015-01-01

Global transformations extend beyond local habitats; therefore, larger-scale approaches are needed to assess community-level responses and resilience to unfolding environmental changes. Using longterm data (1996–2011), we evaluated spatial patterns and functional redundancies in the littoral invertebrate communities of 85 Swedish lakes, with the objective of assessing their potential resilience to environmental change at regional scales (that is, spatial resilience). Multivariate spatial modeling was used to differentiate groups of invertebrate species exhibiting spatial patterns in composition and abundance (that is, deterministic species) from those lacking spatial patterns (that is, stochastic species). We then determined the functional feeding attributes of the deterministic and stochastic invertebrate species, to infer resilience. Between one and three distinct spatial patterns in invertebrate composition and abundance were identified in approximately one-third of the species; the remainder were stochastic. We observed substantial differences in metrics between deterministic and stochastic species. Functional richness and diversity decreased over time in the deterministic group, suggesting a loss of resilience in regional invertebrate communities. However, taxon richness and redundancy increased monotonically in the stochastic group, indicating the capacity of regional invertebrate communities to adapt to change. Our results suggest that a refined picture of spatial resilience emerges if patterns of both the deterministic and stochastic species are accounted for. Spatially extensive monitoring may help increase our mechanistic understanding of community-level responses and resilience to regional environmental change, insights that are critical for developing management and conservation agendas in this current period of rapid environmental transformation.

Differential lead component pulling as a possible mechanism of inside-out abrasion and conductor cable externalization.

PubMed

Lau, Ernest W

2013-09-01

Conductor cable externalization with protrusion (CCE*) is highly prevalent among the Riata 8F and ST 7F defibrillation (DF) leads and infrequently present in the QuickSite and the QuickFlex coronary sinus (CS) leads (St. Jude Medical, Sylmar, CA, USA). A model for CCE* based on differential lead component pulling and conjugate extension with reciprocal compression-bending was developed. Extension of a proximal lead body segment by pectoral or cardiac movements causes reciprocal compression-bending of a distal lead body segment mediated by inextensible conductor cables running down a lead body fixed at various points by fibrous adhesions. The "sawing" action of these cables under tension causes inside-out abrasion of insulation leading to CCE*. DF leads from different manufacturers and the QuickFlex and QuickFlex μ CS leads were subjected to simulated differential pulling. Restitution from differential pulling followed three patterns: complete, partial without escalation, and incomplete with escalation. Only the last pattern (only shown by the Riata 8F and ST 7F leads) was associated with an increased risk to CCE*. For CS leads, deformation concentrated on the more flexible segment when the lead body did not have a uniform construction. The Durata, Riata ST Optim, QuickFlex μ, and Quartet leads should be relatively immune to CCE*. The Durata leads are extremely resistant to longitudinal deformation and probably cause mediastinal displacement rather than differential pulling in response to pectoral movements in vivo. Implantation techniques and lead designs can be used to minimize the risk of CCE*. A bench test for CCE* can be constructed. ©2013, The Author. Journal compilation ©2013 Wiley Periodicals, Inc.

RAGE and TLRs: relatives, friends or neighbours?

PubMed

Ibrahim, Zaridatul Aini; Armour, Carol L; Phipps, Simon; Sukkar, Maria B

2013-12-01

The innate immune system forms the first line of protection against infectious and non-infectious tissue injury. Cells of the innate immune system detect pathogen-associated molecular patterns or endogenous molecules released as a result of tissue injury or inflammation through various innate immune receptors, collectively termed pattern-recognition receptors. Members of the Toll-like receptor (TLR) family of pattern-recognition receptors have well established roles in the host immune response to infection, while the receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor predominantly involved in the recognition of endogenous molecules released in the context of infection, physiological stress or chronic inflammation. RAGE and TLRs share common ligands and signaling pathways, and accumulating evidence points towards their co-operative interaction in the host immune response. At present however, little is known about the mechanisms that result in TLR versus RAGE signalling or RAGE-TLR cross-talk in response to their shared ligands. Here we review what is known in relation to the physicochemical basis of ligand interactions between TLRs and RAGE, focusing on three shared ligands of these receptors: HMGB1, S100A8/A9 and LPS. Our aim is to discuss what is known about differential ligand interactions with RAGE and TLRs and to highlight important areas for further investigation so that we may better understand the role of these receptors and their relationship in host defense. Copyright © 2013 Elsevier Ltd. All rights reserved.

Commensal-Associated Molecular Patterns Induce Selective Toll-Like Receptor-Trafficking from Apical Membrane to Cytoplasmic Compartments in Polarized Intestinal Epithelium

PubMed Central

Cario, Elke; Brown, Dennis; McKee, Mary; Lynch-Devaney, Kathryn; Gerken, Guido; Podolsky, Daniel K.

2002-01-01

Commensal-associated molecular patterns, the major products of nonpathogenic bacteria, are present at high concentrations at the apical surface of the intestinal epithelium. However, the nature of the interaction of commensal-associated molecular patterns with the lumenal surface of the epithelium has not been defined. We have recently demonstrated that intestinal epithelial cells constitutively express several Toll-like receptors (TLRs) in vitro and in vivo that seem to be the key receptors responsible for immune cell activation in response to various bacterial products. In this study we characterize the subcellular distribution of two major TLRs, TLR2 and TLR4, and their ligand-specific dynamic regulation in the model human intestinal epithelial cell line T84. Immunocytochemical studies indicate that TLR2 and TLR4 are constitutively expressed at the apical pole of differentiated T84 cells. After stimulation with lipopolysaccharide or peptidoglycan, TLRs selectively traffic to cytoplasmic compartments near the basolateral membrane. Thus, we demonstrate that TLRs are positioned at the apical pole where they are poised to monitor the sensitive balance of the lumenal microbial array. The results of this dynamic epithelial surveillance can then be conveyed to the underlying cell populations of the lamina propria via these innate immune pattern recognition receptors. PMID:11786410

Developmental expression of Hsp90, Hsp70 and HSF during morphogenesis in the vetigastropod Haliotis asinina.

PubMed

Gunter, Helen M; Degnan, Bernard M

2007-08-01

Heat shock proteins (Hsps) have dual functions, participating in both the stress response and a broad range of developmental processes. At physiological temperatures, it has been demonstrated in deuterostomes (vertebrates) and ecdysozoans (insects) that Hsps are expressed in tissues that are undergoing differentiation and morphogenesis. Here we investigate the developmental expression of Hsp70, Hsp90 and their regulatory transcription factor heat shock transcription factor (HSF) in the marine gastropod Haliotis asinina, a representative of the 3rd major lineage of bilaterian animals, the Lophotrochozoa. HasHsp70, HasHsp90 and HasHSF are maternally expressed in H. asinina and are progressively restricted to the micromere lineage during cleavage. During larval morphogenesis, they are expressed in unique and overlapping patterns in the prototroch, foot, and mantle. Hsp expression peaked in these tissues during periods of cell differentiation and morphogenesis, returning to lower levels after morphogenesis was complete. These patterns of Hsp and HSF expression in H. asinina are akin to those observed in ecdysozoans and deuterostomes, with Hsps being activated in cells and tissues undergoing morphogenesis.

An interspecific fungal hybrid reveals cross-kingdom rules for allopolyploid gene expression patterns.

PubMed

Cox, Murray P; Dong, Ting; Shen, Genggeng; Dalvi, Yogesh; Scott, D Barry; Ganley, Austen R D

2014-03-01

Polyploidy, a state in which the chromosome complement has undergone an increase, is a major force in evolution. Understanding the consequences of polyploidy has received much attention, and allopolyploids, which result from the union of two different parental genomes, are of particular interest because they must overcome a suite of biological responses to this merger, known as "genome shock." A key question is what happens to gene expression of the two gene copies following allopolyploidization, but until recently the tools to answer this question on a genome-wide basis were lacking. Here we utilize high throughput transcriptome sequencing to produce the first genome-wide picture of gene expression response to allopolyploidy in fungi. A novel pipeline for assigning sequence reads to the gene copies was used to quantify their expression in a fungal allopolyploid. We find that the transcriptional response to allopolyploidy is predominantly conservative: both copies of most genes are retained; over half the genes inherit parental gene expression patterns; and parental differential expression is often lost in the allopolyploid. Strikingly, the patterns of gene expression change are highly concordant with the genome-wide expression results of a cotton allopolyploid. The very different nature of these two allopolyploids implies a conserved, eukaryote-wide transcriptional response to genome merger. We provide evidence that the transcriptional responses we observe are mostly driven by intrinsic differences between the regulatory systems in the parent species, and from this propose a mechanistic model in which the cross-kingdom conservation in transcriptional response reflects conservation of the mutational processes underlying eukaryotic gene regulatory evolution. This work provides a platform to develop a universal understanding of gene expression response to allopolyploidy and suggests that allopolyploids are an exceptional system to investigate gene regulatory changes that have evolved in the parental species prior to allopolyploidization.

Relative impact of uniaxial alignment vs. form-induced stress on differentiation of human adipose derived stem cells

PubMed Central

Huang, Samuel; Li, Julie Yi-Shuan; Chien, Shu; Zhang, Kang; Chen, Shaochen

2013-01-01

ADSCs are a great cell source for tissue engineering and regenerative medicine. However, the development of methods to appropriately manipulate these cells in vitro remains a challenge. Here the proliferation and differentiation of ADSCs on microfabricated surfaces with varying geometries were investigated. To create the patterned substrates, a maskless biofabrication method was developed based on dynamic optical projection stereolithography. Proliferation and early differentiation of ADSCs were compared across three distinct multicellular patterns, namely stripes (ST), symmetric fork (SF), and asymmetric fork (AF). The ST pattern was designed for uniaxial cell alignment while the SF and AF pattern were designed with altered cell directionality to different extents. The SF and AF patterns generated similar levels of regional peak stress, which were both significantly higher than those within the ST pattern. No significant difference in ADSC proliferation was observed among the three patterns. In comparison to the ST pattern, higher peak stress levels of the SF and AF patterns were associated with up-regulation of the chondrogenic and osteogenic markers SOX9 and RUNX2. Interestingly, uniaxial cell alignment in the ST pattern seemed to increase the expression of SM22α and smooth muscle α-actin, suggesting an early smooth muscle lineage progression. These results indicate that geometric cues that promote uniaxial alignment might be more potent for myogenesis than those with increased peak stress. Overall, the use of these patterned geometric cues for modulating cell alignment and form-induced stress can serve as a powerful and versatile technique towards controlling differentiation in ADSCs. PMID:24060419

Transcriptional Analysis of Resistance to Low Temperatures in Bermudagrass Crown Tissues

PubMed Central

Melmaiee, Kalpalatha; Anderson, Michael; Elavarthi, Sathya; Guenzi, Arron; Canaan, Patricia

2015-01-01

Bermudagrass (Cynodon dactylon L pers.) is one of the most geographically adapted and utilized of the warm-season grasses. However, bermudagrass adaptation to the Northern USA is limited by freeze damage and winterkill. Our study provides the first large-scale analyses of gene expression in bermudagrass regenerative crown tissues during cold acclimation. We compared gene expression patterns in crown tissues from highly cold tolerant “MSU” and susceptible “Zebra” genotypes exposed to near-freezing temperatures. Suppressive subtractive hybridization was used to isolate putative cold responsive genes Approximately, 3845 transcript sequences enriched for cold acclimation were deposited in the GenBank. A total of 4589 ESTs (3184 unigenes) including 744 ESTs associated with the bermudagrass disease spring dead spot were printed on microarrays and hybridized with cold acclimated complementary Deoxyribonucleic acid (cDNA). A total of 587 differentially expressed unigenes were identified in this study. Of these only 97 (17%) showed significant NCBI matches. The overall expression pattern revealed 40% more down- than up-regulated genes, which was particularly enhanced in MSU compared to Zebra. Among the up-regulated genes 68% were uniquely expressed in MSU (36%) or Zebra (32%). Among the down-regulated genes 40% were unique to MSU, while only 15% to Zebra. Overall expression intensity was significantly higher in MSU than in Zebra (p value ≤ 0.001) and the overall number of genes expressed at 28 days was 2.7 fold greater than at 2 days. These changes in expression patterns reflect the strong genotypic and temporal response to cold temperatures. Additionally, differentially expressed genes from this study can be utilized for developing molecular markers in bermudagrass and other warm season grasses for enhancing cold hardiness. PMID:26348040

Hypoxia regulates microRNA expression in the human carotid body

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

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

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

Gene expression signatures in tree shrew choroid in response to three myopiagenic conditions

PubMed Central

He, Li; Frost, Michael R.; Siegwart, John T.; Norton, Thomas T.

2014-01-01

We examined gene expression in tree shrew choroid in response to three different myopiagenic conditions: minus lens (ML) wear, form deprivation (FD), and continuous darkness (DK). Four groups of tree shrews (n = 7 per group) were used. Starting 24 days after normal eye opening (days of visual experience [DVE]), the ML group wore a monocular −5 D lens for 2 days. The FD group wore a monocular translucent diffuser for 2 days. The DK group experienced continuous darkness binocularly for 11 days, starting at 17 DVE. An age-matched normal group was examined at 26 DVE. Quantitative PCR was used to measure the relative (treated eye vs. control eye) differences in mRNA levels in the choroid for 77 candidate genes. Small myopic changes were observed in the treated eyes (relative to the control eyes) of the ML group (−1.0 ± 0.2 D; mean ± SEM) and FD group (−1.9 ± 0.2 D). A larger myopia developed in the DK group (−4.4 ± 1.0 D) relative to Normal eyes (both groups, mean of right and left eyes). In the ML group, 28 genes showed significant differential mRNA expression; eighteen were down-regulated. A very similar pattern occurred in the FD group; twenty-seven of the same genes were similarly regulated, along with five additional genes. Fewer expression differences in the DK group were significant compared to normal or the control eyes of the ML and FD groups, but the pattern was similar to that of the ML and FD differential expression patterns. These data suggest that, at the level of the choroid, the gene expression signatures produced by “GO” emmetropization signals are highly similar despite the different visual conditions. PMID:25072854

Using facial electromyography to detect preserved emotional processing in disorders of consciousness: A proof-of-principle study.

PubMed

Fiacconi, Chris M; Owen, Adrian M

2016-09-01

To examine whether emotional functioning can be observed in patients who are behaviourally non-responsive using peripheral markers of emotional functioning. We tested two patients, both diagnosed as being in a vegetative state (VS) following hypoxia secondary to cardiac arrest. Thirty-seven healthy participants with no history of neurological illness served as a control group. The activity of two facial muscles (zygomaticus major, corrugator supercilii) was measured using facial electromyography (EMG) to probe for patterned responses that differentiate between auditorily presented joke and non-joke stimuli in VS patients. One of the two VS patients we tested demonstrated greater zygomatic and reduced corrugator activity in response to jokes compared with non-jokes. Critically, these responses followed the pattern and temporal profile of muscle activity observed in our healthy control sample. Despite their behaviorally non-responsive profile, some patients diagnosed as VS appear to retain some aspects of emotional experience. Our findings represent, to our knowledge, the first demonstration that a patient diagnosed as VS can exhibit intact emotional responses to humor as assessed by facial EMG. Therefore, our approach may constitute a feasible bedside tool capable of providing novel insight into the mental and emotional lives of patients who are behaviourally non-responsive. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Evaporation-induced patterns from droplets containing motile and nonmotile bacteria.

PubMed

Nellimoottil, Tittu Thomas; Rao, Pinjala Nagaraju; Ghosh, Siddhartha Sankar; Chattopadhyay, Arun

2007-08-14

In this letter, we report the observations of specific pattern formation from the evaporation of aqueous droplets containing motile and nonmotile bacteria. We found that when motile bacteria were present the droplet evaporated into disclike patterned deposits of bacteria. However, when the bacteria were made nonmotile by treatment with liquid nitrogen, the droplet evaporated into ringlike deposits. We also observed that bacteria with higher motility produced more uniformly deposited disclike patterns. Furthermore, we propose a model with numerical simulations to explain the mechanism of formation of these patterns. The model is based on the advective fluid flow from the center of the droplet toward the edge due to enhanced evaporation from the edge of the pinned droplet in comparison to that from the free surface. For the case of motile bacteria, we have added another velocity parameter toward the axis of the droplet and directed against the fluid flow in order to account for the disclike pattern formation. The numerical simulations match the experimental observations well. The present work, by qualitative and quantitative understanding of the evaporation of bacteria droplets, demonstrates that the inherent bacterial motility is primarily responsible for the formation of these differential patterns.

Cooperativity to increase Turing pattern space for synthetic biology.

PubMed

Diambra, Luis; Senthivel, Vivek Raj; Menendez, Diego Barcena; Isalan, Mark

2015-02-20

It is hard to bridge the gap between mathematical formulations and biological implementations of Turing patterns, yet this is necessary for both understanding and engineering these networks with synthetic biology approaches. Here, we model a reaction-diffusion system with two morphogens in a monostable regime, inspired by components that we recently described in a synthetic biology study in mammalian cells.1 The model employs a single promoter to express both the activator and inhibitor genes and produces Turing patterns over large regions of parameter space, using biologically interpretable Hill function reactions. We applied a stability analysis and identified rules for choosing biologically tunable parameter relationships to increase the likelihood of successful patterning. We show how to control Turing pattern sizes and time evolution by manipulating the values for production and degradation relationships. More importantly, our analysis predicts that steep dose-response functions arising from cooperativity are mandatory for Turing patterns. Greater steepness increases parameter space and even reduces the requirement for differential diffusion between activator and inhibitor. These results demonstrate some of the limitations of linear scenarios for reaction-diffusion systems and will help to guide projects to engineer synthetic Turing patterns.

Temporal and Spatial Variations in Transcriptional Patterns among Closely Related Marine Microbial Taxa

NASA Astrophysics Data System (ADS)

Shilova, I. N.; Robidart, J.; DeLong, E.; Zehr, J. P.

2016-02-01

Marine microbial communities are complex, and even closely related marine microbial populations are genetically and physiologically diverse. Despite such great diversity, conserved and highly synchronized rhythmic transcriptional patterns have been observed in microbial communities worldwide. The current widely used approaches analyzing high-throughput sequence data from microbiomes are not designed to differentiate transcription at strain or ecotype level. We used a novel MicroArray-inspired Gene-Centric (MAGC) bioinformatics approach to discern daily transcription by individual strains in previously analyzed metatranscriptomes from two oceanic regions, California Current System and central North Pacific. The results demonstrated that marine microbial taxa (within cyanobacteria Prochlorococcus and Synechococcus, Alphaproteobacterium Pelagibacter and picoeukaryote Ostreococcus) have unique transcription patterns and respond differentially to variability in space and time in the ocean. For example, the timing of maximum transcription for the photosynthesis and pigments genes varied among Synechococcus strains in the California Current study, likely for optimizing light utilization based on their differences in genetics and physiology. While several Prochlorococcus genotypes were present in the North Pacific study, transcription of the phosphate transporter gene, pstS, in specific genotypes was negatively correlated with phosphate concentrations. These individual transcriptional patterns underlie whole microbial community responses and may be sensitive indicators of environmental conditions, including those associated with long-term environmental change. The MAGC applied here to ocean ecosystems is a promising complementary approach that can enhance the ability to analyze metatranscriptomic data from a variety of environmental microbiomes.

Mechanical Stress Induces Remodeling of Vascular Networks in Growing Leaves

PubMed Central

Bar-Sinai, Yohai; Julien, Jean-Daniel; Sharon, Eran; Armon, Shahaf; Nakayama, Naomi; Adda-Bedia, Mokhtar; Boudaoud, Arezki

2016-01-01

Differentiation into well-defined patterns and tissue growth are recognized as key processes in organismal development. However, it is unclear whether patterns are passively, homogeneously dilated by growth or whether they remodel during tissue expansion. Leaf vascular networks are well-fitted to investigate this issue, since leaves are approximately two-dimensional and grow manyfold in size. Here we study experimentally and computationally how vein patterns affect growth. We first model the growing vasculature as a network of viscoelastic rods and consider its response to external mechanical stress. We use the so-called texture tensor to quantify the local network geometry and reveal that growth is heterogeneous, resembling non-affine deformations in composite materials. We then apply mechanical forces to growing leaves after veins have differentiated, which respond by anisotropic growth and reorientation of the network in the direction of external stress. External mechanical stress appears to make growth more homogeneous, in contrast with the model with viscoelastic rods. However, we reconcile the model with experimental data by incorporating randomness in rod thickness and a threshold in the rod growth law, making the rods viscoelastoplastic. Altogether, we show that the higher stiffness of veins leads to their reorientation along external forces, along with a reduction in growth heterogeneity. This process may lead to the reinforcement of leaves against mechanical stress. More generally, our work contributes to a framework whereby growth and patterns are coordinated through the differences in mechanical properties between cell types. PMID:27074136

The immunohistochemical detection of involucrin in denture induced fibrous inflammatory hyperplasia of oral mucous membrane.

PubMed

Thomas, G A

1991-01-01

Involucrin is a major structural protein specific to the cross-linked cell envelope found in the stratum corneum of stratified squamous epithelium. This protein is considered to be an excellent immunohistochemical marker of normal squamous differentiation. Detection of variations to the patterns of immunostaining for involucrin may also be of value in the differential diagnosis between benign and malignant lesions. Previous studies of involucrin expression in oral mucosa have failed to clarify the effect of chronic inflammatory change upon the patterns of immunoreactivity. This study investigated involucrin staining patterns in fibrous inflammatory hyperplasia of oral mucous membrane (FIH). The results suggest that in FIH an altered pattern of involucrin immunostain occurs in areas of severe inflammatory change. This may reflect changes to the pattern of squamous differentiation in this tissue.

Molecular differentiation between Salmonella enterica subsp enterica serovar Pullorum and Salmonella enterica subsp enterica serovar Gallinarum

PubMed Central

Ribeiro, Simone Alves Mendes; de Paiva, Jaqueline Boldrin; Zotesso, Fábio; Lemos, Manoel Victor Franco; Berchieri Jánior, Ângelo

2009-01-01

S. Pullorum (SP) and S. Gallinarum (SG) are very similar. They are the agents of pullorum disease and fowl typhoid, respectively, and the two diseases are responsible for economic losses in poultry production. Although SP and SG are difficult to be differentiated in routine laboratory procedures, the ability to metabolize ornithine is a biochemical test that may be used to achieve this aim. While SP is able to decarboxylate this amino acid, SG is not. However, the isolation of strains showing atypical biochemical behavior has made this differentiation difficult. One of the genes associated with the metabolization of the amino acid ornithine is called speC, and is found in both serovars. The analysis of 21 SP and 15 SG strains by means of PCR did not enable the differentiation of the two serovars, because fragments produced were identical. However, after enzymatic treatment with restriction enzyme Eco RI, the band pattern of each serovar showed to be different, even in samples of atypical biochemical behavior. This fact enabled the standardization of the technique for a quick and safe differentiation of serovars Pullorum and Gallinarum. PMID:24031341

Substrate micropatterns produced by polymer demixing regulate focal adhesions, actin anisotropy, and lineage differentiation of stem cells.

PubMed

Vega, Sebastián L; Arvind, Varun; Mishra, Prakhar; Kohn, Joachim; Sanjeeva Murthy, N; Moghe, Prabhas V

2018-06-12

Stem cells are adherent cells whose multipotency and differentiation can be regulated by numerous microenvironmental signals including soluble growth factors and surface topography. This study describes a simple method for creating distinct micropatterns via microphase separation resulting from polymer demixing of poly(desaminotyrosyl-tyrosine carbonate) (PDTEC) and polystyrene (PS). Substrates with co-continuous (ribbons) or discontinuous (islands and pits) PDTEC regions were obtained by varying the ratio of PDTEC and sacrificial PS. Human mesenchymal stem cells (MSCs) cultured on co-continuous PDTEC substrates for 3 days in bipotential adipogenic/osteogenic (AD/OS) induction medium showed no change in cell morphology but exhibited increased anisotropic cytoskeletal organization and larger focal adhesions when compared to MSCs cultured on discontinuous micropatterns. After 14 days in bipotential AD/OS induction medium, MSCs cultured on co-continuous micropatterns exhibited increased expression of osteogenic markers, whereas MSCs on discontinuous PDTEC substrates showed a low expression of adipogenic and osteogenic differentiation markers. Substrates with graded micropatterns were able to reproduce the influence of local underlying topography on MSC differentiation, thus demonstrating their potential for high throughput analysis. This work presents polymer demixing as a simple, non-lithographic technique to produce a wide range of micropatterns on surfaces with complex geometries to influence cellular and tissue regenerative responses. Gaining a better understanding of how engineered microenvironments influence stem cell differentiation is integral to increasing the use of stem cells and materials in a wide range of tissue engineering applications. In this study, we show the range of topography obtained by polymer demixing is sufficient for investigating how surface topography affects stem cell morphology and differentiation. Our findings show that co-continuous topographies favor early (3-day) cytoskeletal anisotropy and focal adhesion maturation as well as long-term (14-day) expression of osteogenic differentiation markers. Taken together, this study presents a simple approach to pattern topographies that induce divergent responses in stem cell morphology and differentiation. Copyright © 2018. Published by Elsevier Ltd.

Adapting cultural mixture modeling for continuous measures of knowledge and memory fluency.

PubMed

Tan, Yin-Yin Sarah; Mueller, Shane T

2016-09-01

Previous research (e.g., cultural consensus theory (Romney, Weller, & Batchelder, American Anthropologist, 88, 313-338, 1986); cultural mixture modeling (Mueller & Veinott, 2008)) has used overt response patterns (i.e., responses to questionnaires and surveys) to identify whether a group shares a single coherent attitude or belief set. Yet many domains in social science have focused on implicit attitudes that are not apparent in overt responses but still may be detected via response time patterns. We propose a method for modeling response times as a mixture of Gaussians, adapting the strong-consensus model of cultural mixture modeling to model this implicit measure of knowledge strength. We report the results of two behavioral experiments and one simulation experiment that establish the usefulness of the approach, as well as some of the boundary conditions under which distinct groups of shared agreement might be recovered, even when the group identity is not known. The results reveal that the ability to recover and identify shared-belief groups depends on (1) the level of noise in the measurement, (2) the differential signals for strong versus weak attitudes, and (3) the similarity between group attitudes. Consequently, the method shows promise for identifying latent groups among a population whose overt attitudes do not differ, but whose implicit or covert attitudes or knowledge may differ.

Differential Tuning of Ventral and Dorsal Streams during the Generation of Common and Uncommon Tool Uses.

PubMed

Matheson, Heath E; Buxbaum, Laurel J; Thompson-Schill, Sharon L

2017-11-01

Our use of tools is situated in different contexts. Prior evidence suggests that diverse regions within the ventral and dorsal streams represent information supporting common tool use. However, given the flexibility of object concepts, these regions may be tuned to different types of information when generating novel or uncommon uses of tools. To investigate this, we collected fMRI data from participants who reported common or uncommon tool uses in response to visually presented familiar objects. We performed a pattern dissimilarity analysis in which we correlated cortical patterns with behavioral measures of visual, action, and category information. The results showed that evoked cortical patterns within the dorsal tool use network reflected action and visual information to a greater extent in the uncommon use group, whereas evoked neural patterns within the ventral tool use network reflected categorical information more strongly in the common use group. These results reveal the flexibility of cortical representations of tool use and the situated nature of cortical representations more generally.

The Transcriptome of the Zebrafish Embryo After Chemical Exposure: A Meta-Analysis.

PubMed

Schüttler, Andreas; Reiche, Kristin; Altenburger, Rolf; Busch, Wibke

2017-06-01

Numerous studies have been published in the past years investigating the transcriptome of the zebrafish embryo (ZFE) upon being subjected to chemical stress. Aiming at a more mechanistic understanding of the results of such studies, knowledge about commonalities of transcript regulation in response to chemical stress is needed. Thus, our goal in this study was to identify and interpret genes and gene sets constituting a general response to chemical exposure. Therefore, we aggregated and reanalyzed published toxicogenomics data obtained with the ZFE. We found that overlap of differentially transcribed genes in response to chemical stress across independent studies is generally low and the most commonly differentially transcribed genes appear in less than 50% of all treatments across studies. However, effect size analysis revealed several genes showing a common trend of differential expression, among which genes related to calcium homeostasis emerged as key, especially in exposure settings up to 24 h post-fertilization. Additionally, we found that these and other downregulated genes are often linked to anatomical regions developing during the respective exposure period. Genes showing a trend of increased expression were, among others, linked to signaling pathways (e.g., Wnt, Fgf) as well as lysosomal structures and apoptosis. The findings of this study help to increase the understanding of chemical stress responses in the developing zebrafish embryo and provide a starting point to improve experimental designs for this model system. In future, improved time- and concentration-resolved experiments should offer better understanding of stress response patterns and access to mechanistic information. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology.

Transcriptional response of honey bee larvae infected with the bacterial pathogen Paenibacillus larvae.

PubMed

Cornman, Robert Scott; Lopez, Dawn; Evans, Jay D

2013-01-01

American foulbrood disease of honey bees is caused by the bacterium Paenibacillus larvae. Infection occurs per os in larvae and systemic infection requires a breaching of the host peritrophic matrix and midgut epithelium. Genetic variation exists for both bacterial virulence and host resistance, and a general immunity is achieved by larvae as they age, the basis of which has not been identified. To quickly identify a pool of candidate genes responsive to P. larvae infection, we sequenced transcripts from larvae inoculated with P. larvae at 12 hours post-emergence and incubated for 72 hours, and compared expression levels to a control cohort. We identified 75 genes with significantly higher expression and six genes with significantly lower expression. In addition to several antimicrobial peptides, two genes encoding peritrophic-matrix domains were also up-regulated. Extracellular matrix proteins, proteases/protease inhibitors, and members of the Osiris gene family were prevalent among differentially regulated genes. However, analysis of Drosophila homologs of differentially expressed genes revealed spatial and temporal patterns consistent with developmental asynchrony as a likely confounder of our results. We therefore used qPCR to measure the consistency of gene expression changes for a subset of differentially expressed genes. A replicate experiment sampled at both 48 and 72 hours post infection allowed further discrimination of genes likely to be involved in host response. The consistently responsive genes in our test set included a hymenopteran-specific protein tyrosine kinase, a hymenopteran specific serine endopeptidase, a cytochrome P450 (CYP9Q1), and a homolog of trynity, a zona pellucida domain protein. Of the known honey bee antimicrobial peptides, apidaecin was responsive at both time-points studied whereas hymenoptaecin was more consistent in its level of change between biological replicates and had the greatest increase in expression by RNA-seq analysis.

Parallel Geographic Variation in Drosophila melanogaster

PubMed Central

Reinhardt, Josie A.; Kolaczkowski, Bryan; Jones, Corbin D.; Begun, David J.; Kern, Andrew D.

2014-01-01

Drosophila melanogaster, an ancestrally African species, has recently spread throughout the world, associated with human activity. The species has served as the focus of many studies investigating local adaptation relating to latitudinal variation in non-African populations, especially those from the United States and Australia. These studies have documented the existence of shared, genetically determined phenotypic clines for several life history and morphological traits. However, there are no studies designed to formally address the degree of shared latitudinal differentiation at the genomic level. Here we present our comparative analysis of such differentiation. Not surprisingly, we find evidence of substantial, shared selection responses on the two continents, probably resulting from selection on standing ancestral variation. The polymorphic inversion In(3R)P has an important effect on this pattern, but considerable parallelism is also observed across the genome in regions not associated with inversion polymorphism. Interestingly, parallel latitudinal differentiation is observed even for variants that are not particularly strongly differentiated, which suggests that very large numbers of polymorphisms are targets of spatially varying selection in this species. PMID:24610860

Patterns of Post-Glacial Genetic Differentiation in Marginal Populations of a Marine Microalga

PubMed Central

Tahvanainen, Pia; Alpermann, Tilman J.; Figueroa, Rosa Isabel; John, Uwe; Hakanen, Päivi; Nagai, Satoshi; Blomster, Jaanika; Kremp, Anke

2012-01-01

This study investigates the genetic structure of an eukaryotic microorganism, the toxic dinoflagellate Alexandrium ostenfeldii, from the Baltic Sea, a geologically young and ecologically marginal brackish water estuary which is predicted to support evolution of distinct, genetically impoverished lineages of marine macroorganisms. Analyses of the internal transcribed spacer (ITS) sequences and Amplified Fragment Length Polymorphism (AFLP) of 84 A. ostenfeldii isolates from five different Baltic locations and multiple external sites revealed that Baltic A. ostenfeldii is phylogenetically differentiated from other lineages of the species and micro-geographically fragmented within the Baltic Sea. Significant genetic differentiation (F ST) between northern and southern locations was correlated to geographical distance. However, instead of discrete genetic units or continuous genetic differentiation, the analysis of population structure suggests a complex and partially hierarchic pattern of genetic differentiation. The observed pattern suggests that initial colonization was followed by local differentiation and varying degrees of dispersal, most likely depending on local habitat conditions and prevailing current systems separating the Baltic Sea populations. Local subpopulations generally exhibited low levels of overall gene diversity. Association analysis suggests predominately asexual reproduction most likely accompanied by frequency shifts of clonal lineages during planktonic growth. Our results indicate that the general pattern of genetic differentiation and reduced genetic diversity of Baltic populations found in large organisms also applies to microscopic eukaryotic organisms. PMID:23300940

Expression of c-Fes protein isoforms correlates with differentiation in myeloid leukemias.

PubMed

Carlson, Anne; Berkowitz, Jeanne McAdara; Browning, Damaris; Slamon, Dennis J; Gasson, Judith C; Yates, Karen E

2005-05-01

The cellular fes gene encodes a 93-kilodalton protein-tyrosine kinase (p93) that is expressed in both normal and neoplastic myeloid cells. Increased c-Fes expression is associated with differentiation in normal myeloid cells and cell lines. Our hypothesis was that primary leukemia cells would show a similar pattern of increased expression in more differentiated cells. Therefore, we compared c-Fes expression in cells with an undifferentiated, blast phenotype (acute myelogenous leukemia--AML) to cells with a differentiated phenotype (chronic myelogenous leukemia--CML). Instead of differences in p93 expression levels, we found complex patterns of c-Fes immunoreactive proteins that corresponded with differentiation in normal and leukemic myeloid cells. The "blast" pattern consisted of c-Fes immunoreactive proteins p93, p74, and p70; the "differentiated" pattern showed two additional c-Fes immunoreactive proteins, p67 and p62. Using mRNA from mouse and human cell lines, we found deletion of one or more exons in the c-fes mRNA. Those deletions predicted truncation of conserved domains (CDC15/FCH and SH2) involved in protein-protein interactions. No deletions were found, however, within the kinase domain. We infer that alternative splicing generates a family of c-Fes proteins. This may be a mechanism to direct the c-Fes kinase domain to different subcellular locations and/or substrates at specific stages of myeloid cell differentiation.

Patterns of post-glacial genetic differentiation in marginal populations of a marine microalga.

PubMed

Tahvanainen, Pia; Alpermann, Tilman J; Figueroa, Rosa Isabel; John, Uwe; Hakanen, Päivi; Nagai, Satoshi; Blomster, Jaanika; Kremp, Anke

2012-01-01

This study investigates the genetic structure of an eukaryotic microorganism, the toxic dinoflagellate Alexandrium ostenfeldii, from the Baltic Sea, a geologically young and ecologically marginal brackish water estuary which is predicted to support evolution of distinct, genetically impoverished lineages of marine macroorganisms. Analyses of the internal transcribed spacer (ITS) sequences and Amplified Fragment Length Polymorphism (AFLP) of 84 A. ostenfeldii isolates from five different Baltic locations and multiple external sites revealed that Baltic A. ostenfeldii is phylogenetically differentiated from other lineages of the species and micro-geographically fragmented within the Baltic Sea. Significant genetic differentiation (F(ST)) between northern and southern locations was correlated to geographical distance. However, instead of discrete genetic units or continuous genetic differentiation, the analysis of population structure suggests a complex and partially hierarchic pattern of genetic differentiation. The observed pattern suggests that initial colonization was followed by local differentiation and varying degrees of dispersal, most likely depending on local habitat conditions and prevailing current systems separating the Baltic Sea populations. Local subpopulations generally exhibited low levels of overall gene diversity. Association analysis suggests predominately asexual reproduction most likely accompanied by frequency shifts of clonal lineages during planktonic growth. Our results indicate that the general pattern of genetic differentiation and reduced genetic diversity of Baltic populations found in large organisms also applies to microscopic eukaryotic organisms.

Addressing the selectivity issue of cobalt doped zinc oxide thin film iso-butane sensors: Conductance transients and principal component analyses

NASA Astrophysics Data System (ADS)

Ghosh, A.; Majumder, S. B.

2017-07-01

Iso-butane (i-C4H10) is one of the major components of liquefied petroleum gas which is used as fuel in domestic and industrial applications. Developing chemi-resistive selective i-C4H10 thin film sensors remains a major challenge. Two strategies were undertaken to differentiate carbon monoxide, hydrogen, and iso-butane gases from the measured conductance transients of cobalt doped zinc oxide thin films. Following the first strategy, the response and recovery transients of conductances in these gas environments are fitted using the Langmuir adsorption kinetic model to estimate the heat of adsorption, response time constant, and activation energies for adsorption (response) and desorption (recovery). Although these test gases have seemingly different vapor densities, molecular diameters, and reactivities, analyzing the estimated heat of adsorption and activation energies (for both adsorption and desorption), we could not differentiate these gases unequivocally. However, we have found that the lower the vapor density, the faster the response time irrespective of the test gas concentration. As a second strategy, we demonstrated that feature extraction of conductance transients (using fast Fourier transformation) in conjunction with the pattern recognition algorithm (principal component analysis) is more fruitful to address the cross-sensitivity of Co doped ZnO thin film sensors. We have found that although the dispersion among different concentrations of hydrogen and carbon monoxide could not be avoided, each of these three gases forms distinct clusters in the plot of principal component 2 versus 1 and therefore could easily be differentiated.

Similarities in temperature-dependent gene expression plasticity across timescales in threespine stickleback (Gasterosteus aculeatus).

PubMed

Metzger, David C H; Schulte, Patricia M

2018-04-14

Phenotypic plasticity occurs at a variety of timescales, but little is known about the degree to which plastic responses at different timescales are associated with similar underlying molecular processes, which is critical for assessing the effects of plasticity on evolutionary trajectories. To address this issue, we identified differential gene expression in response to developmental temperature in the muscle transcriptome of adult threespine stickleback (Gasterosteus aculeatus) exposed to 12, 18 and 24°C until hatch and then held at 18°C for 9 months and compared these results to differential gene expression in response to adult thermal acclimation in stickleback developed at 18°C and then acclimated to 5 and 25°C as adults. Adult thermal acclimation affected the expression of 7,940 and 7,015 genes in response to cold and warm acclimation, respectively, and 4,851 of these genes responded in both treatments. In contrast, the expression of only 33 and 29 genes was affected by cold and warm development, respectively. The majority of the genes affected by developmental temperature were also affected by adult acclimation temperature. Many genes that were differentially expressed as a result of adult acclimation were associated with previously identified temperature-dependent effects on DNA methylation patterns, suggesting a role of epigenetic mechanisms in regulating gene expression plasticity during acclimation. Taken together, these results demonstrate similarities between the persistent effects of developmental plasticity on gene expression and the effects of adult thermal acclimation, emphasizing the potential for mechanistic links between plasticity acting at these different life stages. © 2018 John Wiley & Sons Ltd.

Influence of age, sex, and strength training on human muscle gene expression determined by microarray

PubMed Central

ROTH, STEPHEN M.; FERRELL, ROBERT E.; PETERS, DAVID G.; METTER, E. JEFFREY; HURLEY, BEN F.; ROGERS, MARC A.

2010-01-01

The purpose of this study was to determine the influence of age, sex, and strength training (ST) on large-scale gene expression patterns in vastus lateralis muscle biopsies using high-density cDNA microarrays and quantitative PCR. Muscle samples from sedentary young (20–30 yr) and older (65–75 yr) men and women (5 per group) were obtained before and after a 9-wk unilateral heavy resistance ST program. RNA was hybridized to cDNA filter microarrays representing ~4,000 known human genes and comparisons were made among arrays to determine differential gene expression as a result of age and sex differences, and/or response to ST. Sex had the strongest influence on muscle gene expression, with differential expression (>1.7-fold) observed for ~200 genes between men and women (~75% with higher expression in men). Age contributed to differential expression as well, as ~50 genes were identified as differentially expressed (>1.7-fold) in relation to age, representing structural, metabolic, and regulatory gene classes. Sixty-nine genes were identified as being differentially expressed (>1.7-fold) in all groups in response to ST, and the majority of these were downregulated. Quantitative PCR was employed to validate expression levels for caldesmon, SWI/SNF (BAF60b), and four-and-a-half LIM domains 1. These significant differences suggest that in the analysis of skeletal muscle gene expression issues of sex, age, and habitual physical activity must be addressed, with sex being the most critical variable. PMID:12209020

Positive Aspects of Fathering and Mothering, and Children's Attachment in Kindergarten

PubMed Central

George, Melissa R.W.; Cummings, E. Mark; Davies, Patrick T.

2010-01-01

Past research suggests that maternal and paternal parenting processes differentially contribute to children's adjustment. However, the contribution of paternal warmth and responsiveness, to childhood attachment security is less understood, especially beyond the preschool years. The current study examined relations between parenting and attachment among 236 families with children in kindergarten. Parental warmth was virtually unrelated to attachment security and avoidance with mothers and fathers, while paternal and maternal responsiveness to children's emotional distress were uniquely predictive of father- and mother-child attachments, respectively. Although less responsive parenting was related to insecure attachment for both mothers and fathers, the parenting mechanisms associated with insecure attachment differed. Low paternal responsiveness was linked with continuous and categorical assessments of insecure-avoidant attachment, while low maternal responsiveness was associated with insecure-ambivalent attachment. Further research is needed to delineate why these patterns differ for fathers and mothers in order to understand fathers' unique effects on childhood attachment. PMID:20657740

A transcription factor hierarchy defines an environmental stress response network.

PubMed

Song, Liang; Huang, Shao-Shan Carol; Wise, Aaron; Castanon, Rosa; Nery, Joseph R; Chen, Huaming; Watanabe, Marina; Thomas, Jerushah; Bar-Joseph, Ziv; Ecker, Joseph R

2016-11-04

Environmental stresses are universally encountered by microbes, plants, and animals. Yet systematic studies of stress-responsive transcription factor (TF) networks in multicellular organisms have been limited. The phytohormone abscisic acid (ABA) influences the expression of thousands of genes, allowing us to characterize complex stress-responsive regulatory networks. Using chromatin immunoprecipitation sequencing, we identified genome-wide targets of 21 ABA-related TFs to construct a comprehensive regulatory network in Arabidopsis thaliana Determinants of dynamic TF binding and a hierarchy among TFs were defined, illuminating the relationship between differential gene expression patterns and ABA pathway feedback regulation. By extrapolating regulatory characteristics of observed canonical ABA pathway components, we identified a new family of transcriptional regulators modulating ABA and salt responsiveness and demonstrated their utility to modulate plant resilience to osmotic stress. Copyright © 2016, American Association for the Advancement of Science.

Proteomic Characterization of Host Response to Yersinia pestis

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

Chromy, B; Perkins, J; Heidbrink, J

Host-pathogen interactions result in protein expression changes within both the host and the pathogen. Here, results from proteomic characterization of host response following exposure to Yersinia pestis, the causative agent of plague, and to two near neighbors, Y. pseudotuberculosis and Y. enterocolitica, are reported. Human monocyte-like cells were chosen as a model for macrophage immune response to pathogen exposure. Two-dimensional electrophoresis followed by mass spectrometry was used to identify host proteins with differential expression following exposure to these three closely related Yersinia species. This comparative proteomic characterization of host response clearly shows that host protein expression patterns are distinct formore » the different pathogen exposures, and contributes to further understanding of Y. pestis virulence and host defense mechanisms. This work also lays the foundation for future studies aimed at defining biomarkers for presymptomatic detection of plague.« less

Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens

PubMed Central

Chasman, Deborah; Walters, Kevin B.; Lopes, Tiago J. S.; Eisfeld, Amie J.; Kawaoka, Yoshihiro; Roy, Sushmita

2016-01-01

Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection. PMID:27403523

A C. elegans Hox gene switches on, off, on and off again to regulate proliferation, differentiation and morphogenesis.

PubMed

Salser, S J; Kenyon, C

1996-05-01

Hox genes establish body pattern throughout the animal kingdom, but the role these genes play at the cellular level to modify and shape parts of the body remains a mystery. We find that the C. elegans Antennapedia homolog, mab-5, sequentially programs many independent events within individual cell lineages. In one body region, mab-5 first switches ON in a lineage to stimulate proliferation, then OFF to specify epidermal structures, then ON in just one branch of the lineage to promote neuroblast formation, and finally OFF to permit proper sense organ morphology. In a neighboring lineage, continuous mab-5 expression leads to a different pattern of development. Thus, this Hox gene achieves much of its power to diversify the anteroposterior axis through fine spatiotemporal differences in expression coupled with a changing pattern of cellular response.

Organizational justice and mental health: a multi-level test of justice interactions.

PubMed

Fischer, Ronald; Abubakar, Amina; Arasa, Josephine Nyaboke

2014-04-01

We examine main and interaction effects of organizational justice at the individual and the organizational levels on general health in a Kenyan sample. We theoretically differentiate between two different interaction patterns of justice effects: buffering mechanisms based on trust versus intensifying explanations of justice interactions that involve psychological contract violations. Using a two-level hierarchical linear model with responses from 427 employees in 29 organizations, only interpersonal justice at level 1 demonstrated a significant main effect. Interactions between distributive and interpersonal justice at both the individual and the collective levels were found. The intensifying hypothesis was supported: the relationship between distributive justice and mental health problems was strongest when interpersonal justice was high. This contrasts with buffering patterns described in Western samples. We argue that justice interaction patterns shift depending on the economic conditions and sociocultural characteristics of employees studied. © 2013 International Union of Psychological Science.

RNA-seq analysis of the gonadal transcriptome during Alligator mississippiensis temperature-dependent sex determination and differentiation.

PubMed

Yatsu, Ryohei; Miyagawa, Shinichi; Kohno, Satomi; Parrott, Benjamin B; Yamaguchi, Katsushi; Ogino, Yukiko; Miyakawa, Hitoshi; Lowers, Russell H; Shigenobu, Shuji; Guillette, Louis J; Iguchi, Taisen

2016-01-25

The American alligator (Alligator mississippiensis) displays temperature-dependent sex determination (TSD), in which incubation temperature during embryonic development determines the sexual fate of the individual. However, the molecular mechanisms governing this process remain a mystery, including the influence of initial environmental temperature on the comprehensive gonadal gene expression patterns occurring during TSD. Our characterization of transcriptomes during alligator TSD allowed us to identify novel candidate genes involved in TSD initiation. High-throughput RNA sequencing (RNA-seq) was performed on gonads collected from A. mississippiensis embryos incubated at both a male and a female producing temperature (33.5 °C and 30 °C, respectively) in a time series during sexual development. RNA-seq yielded 375.2 million paired-end reads, which were mapped and assembled, and used to characterize differential gene expression. Changes in the transcriptome occurring as a function of both development and sexual differentiation were extensively profiled. Forty-one differentially expressed genes were detected in response to incubation at male producing temperature, and included genes such as Wnt signaling factor WNT11, histone demethylase KDM6B, and transcription factor C/EBPA. Furthermore, comparative analysis of development- and sex-dependent differential gene expression revealed 230 candidate genes involved in alligator sex determination and differentiation, and early details of the suspected male-fate commitment were profiled. We also discovered sexually dimorphic expression of uncharacterized ncRNAs and other novel elements, such as unique expression patterns of HEMGN and ARX. Twenty-five of the differentially expressed genes identified in our analysis were putative transcriptional regulators, among which were MYBL2, MYCL, and HOXC10, in addition to conventional sex differentiation genes such as SOX9, and FOXL2. Inferred gene regulatory network was constructed, and the gene-gene and temperature-gene interactions were predicted. Gonadal global gene expression kinetics during sex determination has been extensively profiled for the first time in a TSD species. These findings provide insights into the genetic framework underlying TSD, and expand our current understanding of the developmental fate pathways during vertebrate sex determination.

Genome-Wide Identification and Expression Analysis of the Mitogen-Activated Protein Kinase Gene Family in Cassava

PubMed Central

Yan, Yan; Wang, Lianzhe; Ding, Zehong; Tie, Weiwei; Ding, Xupo; Zeng, Changying; Wei, Yunxie; Zhao, Hongliang; Peng, Ming; Hu, Wei

2016-01-01

Mitogen-activated protein kinases (MAPKs) play central roles in plant developmental processes, hormone signaling transduction, and responses to abiotic stress. However, no data are currently available about the MAPK family in cassava, an important tropical crop. Herein, 21 MeMAPK genes were identified from cassava. Phylogenetic analysis indicated that MeMAPKs could be classified into four subfamilies. Gene structure analysis demonstrated that the number of introns in MeMAPK genes ranged from 1 to 10, suggesting large variation among cassava MAPK genes. Conserved motif analysis indicated that all MeMAPKs had typical protein kinase domains. Transcriptomic analysis suggested that MeMAPK genes showed differential expression patterns in distinct tissues and in response to drought stress between wild subspecies and cultivated varieties. Interaction networks and co-expression analyses revealed that crucial pathways controlled by MeMAPK networks may be involved in the differential response to drought stress in different accessions of cassava. Expression of nine selected MAPK genes showed that these genes could comprehensively respond to osmotic, salt, cold, oxidative stressors, and abscisic acid (ABA) signaling. These findings yield new insights into the transcriptional control of MAPK gene expression, provide an improved understanding of abiotic stress responses and signaling transduction in cassava, and lead to potential applications in the genetic improvement of cassava cultivars. PMID:27625666

Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head and neck squamous cell carcinoma.

PubMed

Setúbal Destro Rodrigues, Maria Fernanda; Gammon, Luke; Rahman, Muhammad M; Biddle, Adrian; Nunes, Fabio Daumas; Mackenzie, Ian C

2018-03-02

The therapeutic responses of many solid tumours to chemo- and radio-therapies are far from fully effective but therapies targeting malignancy-related cellular changes show promise for further control. In head and neck squamous cell carcinoma, the epidermal growth factor receptor (EGFR) is commonly overexpressed and investigation of agents that block this receptor indicate a limited response when used alone but an ability to enhance the actions of other drugs. The hierarchical stem cell patterns present in tumours generate cellular heterogeneity and this is further complicated by cancer stem cells (CSC) shifting between epithelial (Epi-CSC) and mesenchymal (EMT-CSC) states. To clarify how such heterogeneity influences responses to EGFR blocking, we examined the effects of Cetuximab and Erlotinib on the cell sub-populations in HNSCC cell lines. These agents reduced cell proliferation for all subpopulations but induced little cell death. They did however induce large shifts of cells between the EMT-CSC, Epi-CSC and differentiating cell compartments. Loss of EMT-CSCs reduced cell motility and is expected to reduce invasion and metastasis. EGFR blocking also induced shifts of Epi-CSCs into the differentiating cell compartment which typically has greater sensitivity to chemo/radiation, an effect expected to enhance the overall response of tumour cell populations to adjunctive therapies.

Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head and neck squamous cell carcinoma

PubMed Central

Setúbal Destro Rodrigues, Maria Fernanda; Gammon, Luke; Rahman, Muhammad M.; Biddle, Adrian; Nunes, Fabio Daumas; Mackenzie, Ian C.

2018-01-01

The therapeutic responses of many solid tumours to chemo- and radio-therapies are far from fully effective but therapies targeting malignancy-related cellular changes show promise for further control. In head and neck squamous cell carcinoma, the epidermal growth factor receptor (EGFR) is commonly overexpressed and investigation of agents that block this receptor indicate a limited response when used alone but an ability to enhance the actions of other drugs. The hierarchical stem cell patterns present in tumours generate cellular heterogeneity and this is further complicated by cancer stem cells (CSC) shifting between epithelial (Epi-CSC) and mesenchymal (EMT-CSC) states. To clarify how such heterogeneity influences responses to EGFR blocking, we examined the effects of Cetuximab and Erlotinib on the cell sub-populations in HNSCC cell lines. These agents reduced cell proliferation for all subpopulations but induced little cell death. They did however induce large shifts of cells between the EMT-CSC, Epi-CSC and differentiating cell compartments. Loss of EMT-CSCs reduced cell motility and is expected to reduce invasion and metastasis. EGFR blocking also induced shifts of Epi-CSCs into the differentiating cell compartment which typically has greater sensitivity to chemo/radiation, an effect expected to enhance the overall response of tumour cell populations to adjunctive therapies. PMID:29568372

Choice of tracks, microtubules and/or actin filaments for chloroplast photo-movement is differentially controlled by phytochrome and a blue light receptor.

PubMed

Sato, Y; Wada, M; Kadota, A

2001-01-01

Light induced chloroplast movement has been studied as a model system for photoreception and actin microfilament (MF)-based intracellular motilities in plants. Chloroplast photo-accumulation and -avoidance movement is mediated by phytochrome as well as blue light (BL) receptor in the moss Physcomitrella patens. Here we report the discovery of an involvement of a microtubule (MT)-based system in addition to an MF-based system in photorelocation of chloroplasts in this moss. In the dark, MTs provided tracks for rapid movement of chloroplasts in a longitudinal direction and MFs contributed the tracks for slow movement in any direction. We found that phytochrome responses utilized only the MT-based system, while BL responses had an alternative way of moving, either along MTs or MFs. MT-based systems were mediated by both photoreceptors, but chloroplasts showed movements with different velocity and pattern between them. No apparent difference in the behavior of chloroplast movement between the accumulation and avoidance movement was detected in phytochrome responses or BL responses, except for the direction of the movement. The results presented here demonstrate that chloroplasts use both MTs and MFs for motility and that phytochrome and a BL receptor control directional photo-movement of chloroplasts through the differential regulation of these motile systems.

Cognitive Load Differentially Impacts Response Control in Girls and Boys with ADHD

PubMed Central

Mostofsky, Stewart H.; Rosch, Keri S.

2015-01-01

Children with attention-deficit hyperactivity disorder (ADHD) consistently show impaired response control, including deficits in response inhibition and increased intrasubject variability (ISV) compared to typically-developing (TD) children. However, significantly less research has examined factors that may influence response control in individuals with ADHD, such as task or participant characteristics. The current study extends the literature by examining the impact of increasing cognitive demands on response control in a large sample of 81children with ADHD (40 girls) and 100 TD children (47 girls), ages 8–12 years. Participants completed a simple Go/No-Go (GNG) task with minimal cognitive demands, and a complex GNG task with increased cognitive load. Results showed that increasing cognitive load differentially impacted response control (commission error rate and tau, an ex-Gaussian measure of ISV) for girls, but not boys, with ADHD compared to same-sex TD children. Specifically, a sexually dimorphic pattern emerged such that boys with ADHD demonstrated higher commission error rate and tau on both the simple and complex GNG tasks as compared to TD boys, whereas girls with ADHD did not differ from TD girls on the simple GNG task, but showed higher commission error rate and tau on the complex GNG task. These findings suggest that task complexity influences response control in children with ADHD in a sexually dimorphic manner. The findings have substantive implications for the pathophysiology of ADHD in boys versus girls with ADHD. PMID:25624066

Differential roles of ventral pallidum subregions during cocaine self-administration behaviors

PubMed Central

Root, David H.; Ma, Sisi; Barker, David J.; Megehee, Laura; Striano, Brendan M.; Ralston, Carla M.; Fabbricatore, Anthony T.; West, Mark O.

2012-01-01

The ventral pallidum (VP) is necessary for drug-seeking behavior. VP contains ventromedial (VPvm) and dorsolateral (VPdl) subregions which receive projections from the nucleus accumbens shell and core, respectively. To date, no study has investigated the behavioral functions of the VPdl and VPvm subregions. To address this issue, we investigated whether changes in firing rate (FR) differed between VP subregions during four events: approaching toward, responding on, or retreating away from a cocaine-reinforced operandum, and a cocaine-associated cue. Baseline FR and waveform characteristics did not differ between subregions. VPdl neurons exhibited a greater change in FR compared to VPvm neurons during approaches toward, as well as responses on, the cocaine-reinforced operandum. VPdl neurons were more likely to exhibit a similar change in FR (direction and magnitude) during approach and response than VPvm neurons. In contrast, VPvm firing patterns were heterogeneous, changing FRs during approach or response alone, or both. VP neurons did not discriminate cued behaviors from uncued behaviors. No differences were found between subregions during the retreat and no VP neurons exhibited patterned changes in FR in response to the cocaine-associated cue. The stronger, sustained FR changes of VPdl neurons during approach and response may implicate VPdl in the processing of drug-seeking and drug-taking behavior via projections to subthalamic nucleus and substantia nigra pars reticulata. In contrast, heterogeneous firing patterns of VPvm neurons may implicate VPvm in facilitating mesocortical structures with information related to the sequence of behaviors predicting cocaine self-infusions via projections to mediodorsal thalamus and ventral tegmental area. PMID:22806483

The influence of pigmentation patterning on bumblebee foraging from flowers of Antirrhinum majus

NASA Astrophysics Data System (ADS)

Whitney, Heather M.; Milne, Georgina; Rands, Sean A.; Vignolini, Silvia; Martin, Cathie; Glover, Beverley J.

2013-03-01

Patterns of pigmentation overlying the petal vasculature are common in flowering plants and have been postulated to play a role in pollinator attraction. Previous studies report that such venation patterning is significantly more attractive to bee foragers in the field than ivory or white flowers without veins. To dissect the ways in which venation patterning of pigment can influence bumblebee behaviour, we investigated the response of flower-naïve individuals of Bombus terrestris to veined, ivory and red near-isogenic lines of Antirrhinum majus. We find that red venation shifts flower colour slightly, although the ivory background is the dominant colour. Bees were readily able to discriminate between ivory and veined flowers under differential conditioning but showed no innate preference when presented with a free choice of rewarding ivory and veined flowers. In contrast, both ivory and veined flowers were selected significantly more often than were red flowers. We conclude that advantages conferred by venation patterning might stem from bees learning of their use as nectar guides, rather than from any innate preference for striped flowers.

Population-Level Transcriptomic Responses of the Southern Ocean Salp Salpa thompsoni to Environment Variability of the Western Antarctic Peninsula Region

NASA Astrophysics Data System (ADS)

Bucklin, A. C.; Batta Lona, P. G.; Maas, A. E.; O'Neill, R. J.; Wiebe, P. H.

2015-12-01

In response to the changing Antarctic climate, the Southern Ocean salp Salpa thompsoni has shown altered patterns of distribution and abundance that are anticipated to have profound impacts on pelagic food webs and ecosystem dynamics. The physiological and molecular processes that underlay ecological function and biogeographical distribution are key to understanding present-day dynamics and predicting future trajectories. This study examined transcriptome-wide patterns of gene expression in relation to biological and physical oceanographic conditions in coastal, shelf and offshore waters of the Western Antarctic Peninsula (WAP) region during austral spring and summer 2011. Based on field observations and collections, seasonal changes in the distribution and abundance of salps of different life stages were associated with differences in water mass structure of the WAP. Our observations are consistent with previous suggestions that bathymetry and currents in Bransfield Strait could generate a retentive cell for an overwintering population of S. thompsoni, which may generate the characteristic salp blooms found throughout the region later in summer. The statistical analysis of transcriptome-wide patterns of gene expression revealed differences among salps collected in different seasons and from different habitats (i.e., coastal versus offshore) in the WAP. Gene expression patterns also clustered by station in austral spring - but not summer - collections, suggesting stronger heterogeneity of environmental conditions. During the summer, differentially expressed genes covered a wider range of functions, including those associated with stress responses. Future research using novel molecular transcriptomic / genomic characterization of S. thompsoni will allow more complete understanding of individual-, population-, and species-level responses to environmental variability and prediction of future dynamics of Southern Ocean food webs and ecosystems.

Selection of intracellular calcium patterns in a model with clustered Ca2+ release channels

NASA Astrophysics Data System (ADS)

Shuai, J. W.; Jung, P.

2003-03-01

A two-dimensional model is proposed for intracellular Ca2+ waves, which incorporates both the discrete nature of Ca2+ release sites in the endoplasmic reticulum membrane and the stochastic dynamics of the clustered inositol 1,4,5-triphosphate (IP3) receptors. Depending on the Ca2+ diffusion coefficient and concentration of IP3, various spontaneous Ca2+ patterns, such as calcium puffs, local waves, abortive waves, global oscillation, and tide waves, can be observed. We further investigate the speed of the global waves as a function of the IP3 concentration and the Ca2+ diffusion coefficient and under what conditions the spatially averaged Ca2+ response can be described by a simple set of ordinary differential equations.

A morphometric analysis of cellular differentiation in caps of primary and lateral roots of Helianthus annuus

NASA Technical Reports Server (NTRS)

Moore, R.

1985-01-01

In order to determine if patterns of cell differentiation are similar in primary and lateral roots, I performed a morphometric analysis of the ultrastructure of calyptrogen, columella, and peripheral cells in primary and lateral roots of Helianthus annuus. Each cell type is characterized by a unique ultrastructure, and the ultrastructural changes characteristic of cellular differentiation in root caps are organelle specific. No major structural differences exist in the structures of the composite cell types, or in patterns of cell differentiation in caps of primary vs. lateral roots.

High cell density suppresses BMP4-induced differentiation of human pluripotent stem cells to produce macroscopic spatial patterning in a unidirectional perfusion culture chamber.

PubMed

Tashiro, Shota; Le, Minh Nguyen Tuyet; Kusama, Yuta; Nakatani, Eri; Suga, Mika; Furue, Miho K; Satoh, Taku; Sugiura, Shinji; Kanamori, Toshiyuki; Ohnuma, Kiyoshi

2018-04-19

Spatial pattern formation is a critical step in embryogenesis. Bone morphogenetic protein 4 (BMP4) and its inhibitors are major factors for the formation of spatial patterns during embryogenesis. However, spatial patterning of the human embryo is unclear because of ethical issues and isotropic culture environments resulting from conventional culture dishes. Here, we utilized human pluripotent stem cells (hiPSCs) and a simple anisotropic (unidirectional perfusion) culture chamber, which creates unidirectional conditions, to measure the cell community effect. The influence of cell density on BMP4-induced differentiation was explored during static culture using a conventional culture dish. Immunostaining of the early differentiation marker SSEA-1 and the mesendoderm marker BRACHYURY revealed that high cell density suppressed differentiation, with small clusters of differentiated and undifferentiated cells formed. Addition of five-fold higher concentration of BMP4 showed similar results, suggesting that suppression was not caused by depletion of BMP4 but rather by high cell density. Quantitative RT-PCR array analysis showed that BMP4 induced multi-lineage differentiation, which was also suppressed under high-density conditions. We fabricated an elongated perfusion culture chamber, in which proteins were transported unidirectionally, and hiPSCs were cultured with BMP4. At low density, the expression was the same throughout the chamber. However, at high density, SSEA-1 and BRACHYURY were expressed only in upstream cells, suggesting that some autocrine/paracrine factors inhibited the action of BMP4 in downstream cells to form the spatial pattern. Human iPSCs cultured in a perfusion culture chamber might be useful for studying in vitro macroscopic pattern formation in human embryogenesis. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Emended descriptions of Prevotella denticola, Prevotella loescheii, Prevotella veroralis, and Prevotella melaninogenica.

PubMed

Wu, C C; Johnson, J L; Moore, W E; Moore, L V

1992-10-01

During studies of human periodontal disease, a number of bacterial strains were encountered that, on the basis of results of standard biochemical tests, appeared to be Prevotella buccalis, Prevotella denticola, Prevotella melaninogenica, or Prevotella loescheii. However, use of the standard biochemical tests, cellular fatty acid analyses, and the polyacrylamide gel electrophoresis patterns of soluble proteins resulted in conflicting identifications of these strains. The results of tests for cellobiose fermentation, inulin fermentation, and pigment production were responsible for most of the discordant results. Cellular fatty acid analyses in which the Microbial Identification System was used did not differentiate these strains from validly described species, even though separate library entries were created for them. DNA reassociation determinations in which the S1 nuclease procedure was used showed that cellobiose fermentation and pigment production are variable among strains of P. melaninogenica and P. denticola and that fermentation of xylan is not a reliable characteristic for differentiating P. buccalis from Prevotella veroralis. In contrast to previous indications, most strains of P. veroralis do not ferment xylan. These species can be differentiated by DNA-DNA reassociation and by cellular fatty acid analysis, using the Microbial Identification System, but differentiation by currently described phenotypic characteristics is not reliable. Similarly, P. loescheii and the genetically distinct (but closely related) D1C-20 group cannot be distinguished reliably from each other or from P. veroralis, P. denticola, and P. melaninogenica on the basis of currently described phenotypic tests other than cellular fatty acid composition or, for some species, electrophoretic patterns of soluble whole-cell proteins.

Reconstructing the regulatory circuit of cell fate determination in yeast mating response.

PubMed

Shao, Bin; Yuan, Haiyu; Zhang, Rongfei; Wang, Xuan; Zhang, Shuwen; Ouyang, Qi; Hao, Nan; Luo, Chunxiong

2017-07-01

Massive technological advances enabled high-throughput measurements of proteomic changes in biological processes. However, retrieving biological insights from large-scale protein dynamics data remains a challenging task. Here we used the mating differentiation in yeast Saccharomyces cerevisiae as a model and developed integrated experimental and computational approaches to analyze the proteomic dynamics during the process of cell fate determination. When exposed to a high dose of mating pheromone, the yeast cell undergoes growth arrest and forms a shmoo-like morphology; however, at intermediate doses, chemotropic elongated growth is initialized. To understand the gene regulatory networks that control this differentiation switch, we employed a high-throughput microfluidic imaging system that allows real-time and simultaneous measurements of cell growth and protein expression. Using kinetic modeling of protein dynamics, we classified the stimulus-dependent changes in protein abundance into two sources: global changes due to physiological alterations and gene-specific changes. A quantitative framework was proposed to decouple gene-specific regulatory modes from the growth-dependent global modulation of protein abundance. Based on the temporal patterns of gene-specific regulation, we established the network architectures underlying distinct cell fates using a reverse engineering method and uncovered the dose-dependent rewiring of gene regulatory network during mating differentiation. Furthermore, our results suggested a potential crosstalk between the pheromone response pathway and the target of rapamycin (TOR)-regulated ribosomal biogenesis pathway, which might underlie a cell differentiation switch in yeast mating response. In summary, our modeling approach addresses the distinct impacts of the global and gene-specific regulation on the control of protein dynamics and provides new insights into the mechanisms of cell fate determination. We anticipate that our integrated experimental and modeling strategies could be widely applicable to other biological systems.

Presence of Antigen-Experienced T Cells with Low Grade of Differentiation and Proliferative Potential in Chronic Chagas Disease Myocarditis

PubMed Central

Cabeza-Meckert, Patricia; Viotti, Rodolfo; Garelli, Fernando; Favaloro, Liliana E.; Favaloro, Roberto R.; Laguens, Rubén; Laucella, Susana A.

2014-01-01

Background The main consequence of chronic Trypanosoma cruzi infection is the development of myocarditis in approximately 20–30% of infected individuals but not until 10–20 years after the initial infection. We have previously shown that circulating interferon-γ-secreting T cells responsive to Trypanosoma cruzi antigens in chronic Chagas disease patients display a low grade of differentiation and the frequency of these T lymphocytes decreases along with the severity of heart disease. This study thought to explore the expression of inhibitory receptors, transcription factors of type 1 or regulatory T cells, and markers of T cell differentiation, immunosenescence or active cell cycle in cardiac explants from patients with advanced Chagas disease myocarditis. Methodology/Principal Findings The expression of different markers for T and B cells as well as for macrophages was evaluated by immunohistochemistry and immunofluorescence techniques in cardiac explants from patients with advanced chronic Chagas disease submitted to heart transplantation. Most infiltrating cells displayed markers of antigen-experienced T cells (CD3+, CD4+, CD8+, CD45RO+) with a low grade of differentiation (CD27+, CD57−, CD45RA−, PD-1−). A skewed T helper1/T cytotoxic 1 profile was supported by the expression of T-bet; whereas FOXP3+ cells were scarce and located only in areas of severe myocarditis. In addition, a significant proliferative capacity of CD3+ T cells, assessed by Ki67 staining, was found. Conclusions/Significance The quality of T cell responses and immunoregulatory mechanisms might determine the pattern of the cellular response and the severity of disease in chronic Trypanosoma cruzi infection. PMID:25144227

Nematodes as Sentinels of Heavy Metals and Organic Toxicants in the Soil

PubMed Central

Ekschmitt, Klemens; Korthals, Gerard W.

2006-01-01

Field and laboratory research has repeatedly shown that free-living soil nematodes differ in their sensitivity to soil pollution. In this paper, we analyze whether nematode genera proved sensitive or tolerant toward heavy metals and organic pollutants in six long-term field experiments. We discuss overlaps between nematode physiological responses to heavy metals and to organic pollutants, which may explain why nematodes can exhibit co-tolerance toward several contaminants. We propose a simple method for separating direct effects of soil contamination on nematode populations from indirect effects mediated through the food chain. Finally, we analyze the extent to which nematodes exhibited consistent responses across the experiments analyzed. Our results show that (a) indirect effects of pollution were generally strong; (b) fewer nematode genera were tolerant than sensitive; (c) many genera, including practically all Adenophorea, exhibited a common response pattern to contaminants; and (d) several genera of the Secernentea exhibited differential tolerance toward particular pollutants. We conclude that bioindication of soil contamination should preferentially be based on tolerant, and less on sensitive, nematodes. We provide a list of nematode genera that may potentially serve as differential bioindicators for specific soil contaminants. PMID:19259425

Morphological responses of macrobenthic polychaetes to low oxygen on the Oman continental slope, NW Arabian Sea

NASA Astrophysics Data System (ADS)

Lamont, Peter A.; Gage, John D.

2000-01-01

Morphological adaptation to low dissolved oxygen consisting of enlarged respiratory surface area is described in polychaete species belonging to the family Spionidae from the Oman margin where the oxygen minimum zone impinges on the continental slope. Similar adaptation is suggested for species in the family Cossuridae. Such morphological adaptation apparently has not been previously recorded among polychaetes living in hypoxic conditions. The response consists of enlargement in size and branching of the branchiae relative to similar species living in normal levels of dissolved oxygen. Specimens were examined in benthic samples from different depths along a transect through the oxygen minimum zone. There was a highly significant trend shown to increasing respiratory area relative to body size in two undescribed spionid species with decreasing depth and oxygen within the OMZ. Yet the size and number of branchiae are often used as taxonomic characters. These within-species differences in size and number of branchiae may be a direct response by the phenotype to intensity of hypoxia. The alternative explanations are that they either reflect a pattern of differential post-settlement selection among a highly variable genotype, or represent early genetic differentiation among depth-isolated sub-populations.

Soybean defense responses to the soybean aphid.

PubMed

Li, Yan; Zou, Jijun; Li, Min; Bilgin, Damla D; Vodkin, Lila O; Hartman, Glen L; Clough, Steven J

2008-01-01

Transcript profiles in aphid (Aphis glycines)-resistant (cv. Dowling) and -susceptible (cv. Williams 82) soybean (Glycine max) cultivars using soybean cDNA microarrays were investigated. Large-scale soybean cDNA microarrays representing approx. 18 000 genes or c. 30% of the soybean genome were compared at 6 and 12 h post-application of aphids. In a separate experiment utilizing clip cages, expression of three defense-related genes were examined at 6, 12, 24, 48, and 72 h in both cultivars by quantitative real-time PCR. One hundred and forty genes showed specific responses for resistance; these included genes related to cell wall, defense, DNA/RNA, secondary metabolism, signaling and other processes. When an extended time period of sampling was investigated, earlier and greater induction of three defense-related genes was observed in the resistant cultivar; however, the induction declined after 24 or 48 h in the resistant cultivar but continued to increase in the susceptible cultivar after 24 h. Aphid-challenged resistant plants showed rapid differential gene expression patterns similar to the incompatible response induced by avirulent Pseudomonas syringae. Five genes were identified as differentially expressed between the two genotypes in the absence of aphids.

The Plasma Concentration of the B Cell Activating Factor Is Increased in Children With Acute Malaria

PubMed Central

Nduati, Eunice; Gwela, Agnes; Karanja, Henry; Mugyenyi, Cleopatra; Langhorne, Jean; Marsh, Kevin

2011-01-01

Malaria-specific antibody responses in children often appear to be short-lived but the mechanisms underlying this phenomenon are not well understood. In this study, we investigated the relationship between the B-cell activating factor (BAFF) and its receptors expressed on B cells with antibody responses during and after acute malaria in children. Our results demonstrate that BAFF plasma levels increased during acute malarial disease and reflected disease severity. The expression profiles for BAFF receptors on B cells agreed with rapid activation and differentiation of a proportion of B cells to plasma cells. However, BAFF receptor (BAFF-R) expression was reduced on all peripheral blood B cells during acute infection, but those children with the highest level of BAFF-R expression on B cells maintained schizont-specific immunoglobin G (IgG) over a period of 4 months, indicating that dysregulation of BAFF-R expression on B cells may contribute to short-lived antibody responses to malarial antigens in children. In summary, this study suggests a potential role for BAFF during malaria disease, both as a marker for disease severity and in shaping the differentiation pattern of antigen-specific B cells. PMID:21849293

Effects of Coating a Titanium Alloy with Fibronectin on the Expression of Osteoblast Gene Markers in the MC3T3 Osteoprogenitor Cell Line

PubMed Central

Rapuano, Bruce E.; Hackshaw, Kyle M.; Schniepp, Hannes C.; MacDonald, Daniel E.

2013-01-01

Purpose A number of environmental and patient-related factors contribute to implant failure. A significant fraction of these failures can be attributed to limited osseointegration resulting from poor bone healing responses. The overall goal of this study was to determine whether surface treatment of a titanium-aluminum-vanadium alloy (Ti-6Al-4V) implant material with a biomimetic protein coating could promote the differentiation of attached osteoblastic cells. The specific aims of the study were to investigate whether osteoprogenitor cells cultured on a rigorously cleaned implant specimen showed a normal pattern of differentiation and whether preadsorbed fibronectin accelerated or enhanced osteoblast differentiation. Materials and Methods Ti-6Al-4V disks were rigorously cleaned, passivated in nitric acid, and dry heat–sterilized; some of the disks were then coated with 1 nmol/L fibronectin. MC3T3 osteoprogenitor cells were then cultured on the pretreated disks for several weeks. Quantitative real-time polymerase chain reaction was performed to measure changes over time in the mRNA levels of osteoblast genes. Results Fibronectin increased the peak expression of all analyzed osteoblast gene markers. “Early” genes that normally mark the proliferative phase (0 to 10 days) of osteoblastic development showed peak expression within the first 10 days after cell attachment to the titanium alloy. In contrast, “late” genes that normally mark the differentiation (10 to 20 days) and mineralization (20 to 36 days) phases of osteoblastogenesis achieved peak expression only after approximately 3 to 4 weeks of culture. Conclusions Osteoprogenitors cultured on a rigorously cleaned Ti-6Al-4V alloy were found to demonstrate a normal pattern of osteoblast differentiation. Preadsorbed fibronectin was observed to stimulate osteoblast differentiation during the mineralization phase of osteoblastogenesis. PMID:23057020

An Electrophysiological Index of Perceptual Goodness

PubMed Central

Makin, Alexis D.J.; Wright, Damien; Rampone, Giulia; Palumbo, Letizia; Guest, Martin; Sheehan, Rhiannon; Cleaver, Helen; Bertamini, Marco

2016-01-01

A traditional line of work starting with the Gestalt school has shown that patterns vary in strength and salience; a difference in “Perceptual goodness.” The Holographic weight of evidence model quantifies goodness of visual regularities. The key formula states that W = E/N, where E is number of holographic identities in a pattern and N is number of elements. We tested whether W predicts the amplitude of the neural response to regularity in an extrastriate symmetry-sensitive network. We recorded an Event Related Potential (ERP) generated by symmetry called the Sustained Posterior Negativity (SPN). First, we reanalyzed the published work and found that W explained most variance in SPN amplitude. Then in four new studies, we confirmed specific predictions of the holographic model regarding 1) the differential effects of numerosity on reflection and repetition, 2) the similarity between reflection and Glass patterns, 3) multiple symmetries, and 4) symmetry and anti-symmetry. In all cases, the holographic approach predicted SPN amplitude remarkably well; particularly in an early window around 300–400 ms post stimulus onset. Although the holographic model was not conceived as a model of neural processing, it captures many details of the brain response to symmetry. PMID:27702812

Brain Activation in Response to Visually Evoked Sexual Arousal in Male-to-Female Transsexuals: 3.0 Tesla Functional Magnetic Resonance Imaging

PubMed Central

Oh, Seok-Kyun; Kim, Gwang-Won; Yang, Jong-Chul; Kim, Seok-Kwun; Kang, Heoung-Keun

2012-01-01

Objective This study used functional magnetic resonance imaging (fMRI) to contrast the differential brain activation patterns in response to visual stimulation with both male and female erotic nude pictures in male-to-female (MTF) transsexuals who underwent a sex reassignment surgery. Materials and Methods A total of nine healthy MTF transsexuals after a sex reassignment surgery underwent fMRI on a 3.0 Tesla MR Scanner. The brain activation patterns were induced by visual stimulation with both male and female erotic nude pictures. Results The sex hormone levels of the postoperative MTF transsexuals were in the normal range of healthy heterosexual females. The brain areas, which were activated by viewing male nude pictures when compared with viewing female nude pictures, included predominantly the cerebellum, hippocampus, putamen, anterior cingulate gyrus, head of caudate nucleus, amygdala, midbrain, thalamus, insula, and body of caudate nucleus. On the other hand, brain activation induced by viewing female nude pictures was predominantly observed in the hypothalamus and the septal area. Conclusion Our findings suggest that distinct brain activation patterns associated with visual sexual arousal in postoperative MTF transsexuals reflect their sexual orientation to males. PMID:22563262

Denoising by coupled partial differential equations and extracting phase by backpropagation neural networks for electronic speckle pattern interferometry.

PubMed

Tang, Chen; Lu, Wenjing; Chen, Song; Zhang, Zhen; Li, Botao; Wang, Wenping; Han, Lin

2007-10-20

We extend and refine previous work [Appl. Opt. 46, 2907 (2007)]. Combining the coupled nonlinear partial differential equations (PDEs) denoising model with the ordinary differential equations enhancement method, we propose the new denoising and enhancing model for electronic speckle pattern interferometry (ESPI) fringe patterns. Meanwhile, we propose the backpropagation neural networks (BPNN) method to obtain unwrapped phase values based on a skeleton map instead of traditional interpolations. We test the introduced methods on the computer-simulated speckle ESPI fringe patterns and experimentally obtained fringe pattern, respectively. The experimental results show that the coupled nonlinear PDEs denoising model is capable of effectively removing noise, and the unwrapped phase values obtained by the BPNN method are much more accurate than those obtained by the well-known traditional interpolation. In addition, the accuracy of the BPNN method is adjustable by changing the parameters of networks such as the number of neurons.

Trustworthiness and Negative Affect Predict Economic Decision-Making.

PubMed

Nguyen, Christopher M; Koenigs, Michael; Yamada, Torricia H; Teo, Shu Hao; Cavanaugh, Joseph E; Tranel, Daniel; Denburg, Natalie L

2011-09-01

The Ultimatum Game (UG) is a widely used and well-studied laboratory model of economic decision-making. Here, we studied 129 healthy adults and compared demographic (i.e., age, gender, education), cognitive (i.e., intelligence, attention/working memory, speed, language, visuospatial, memory, executive functions), and personality (i.e., "Big Five", positive affect, negative affect) variables between those with a "rational" versus an "irrational" response pattern on the UG. Our data indicated that participants with "rational" UG performance (accepting any offer, no matter the fairness) endorsed higher levels of trust, or the belief in the sincerity and good intentions of others, while participants with "irrational" UG performance (rejecting unfair offers) endorsed higher levels of negative affect, such as anger and contempt. These personality variables were the only ones that differentiated the two response patterns-demographic and cognitive factors did not differ between rational and irrational players. The results indicate that the examination of personality and affect is crucial to our understanding of the individual differences that underlie decision-making.

Antibacterial titanium nano-patterned arrays inspired by dragonfly wings

NASA Astrophysics Data System (ADS)

Bhadra, Chris M.; Khanh Truong, Vi; Pham, Vy T. H.; Al Kobaisi, Mohammad; Seniutinas, Gediminas; Wang, James Y.; Juodkazis, Saulius; Crawford, Russell J.; Ivanova, Elena P.

2015-11-01

Titanium and its alloys remain the most popular choice as a medical implant material because of its desirable properties. The successful osseointegration of titanium implants is, however, adversely affected by the presence of bacterial biofilms that can form on the surface, and hence methods for preventing the formation of surface biofilms have been the subject of intensive research over the past few years. In this study, we report the response of bacteria and primary human fibroblasts to the antibacterial nanoarrays fabricated on titanium surfaces using a simple hydrothermal etching process. These fabricated titanium surfaces were shown to possess selective bactericidal activity, eliminating almost 50% of Pseudomonas aeruginosa cells and about 20% of the Staphylococcus aureus cells coming into contact with the surface. These nano-patterned surfaces were also shown to enhance the aligned attachment behavior and proliferation of primary human fibroblasts over 10 days of growth. These antibacterial surfaces, which are capable of exhibiting differential responses to bacterial and eukaryotic cells, represent surfaces that have excellent prospects for biomedical applications.

Antibacterial titanium nano-patterned arrays inspired by dragonfly wings

PubMed Central

Bhadra, Chris M.; Khanh Truong, Vi; Pham, Vy T. H.; Al Kobaisi, Mohammad; Seniutinas, Gediminas; Wang, James Y.; Juodkazis, Saulius; Crawford, Russell J.; Ivanova, Elena P.

2015-01-01

Titanium and its alloys remain the most popular choice as a medical implant material because of its desirable properties. The successful osseointegration of titanium implants is, however, adversely affected by the presence of bacterial biofilms that can form on the surface, and hence methods for preventing the formation of surface biofilms have been the subject of intensive research over the past few years. In this study, we report the response of bacteria and primary human fibroblasts to the antibacterial nanoarrays fabricated on titanium surfaces using a simple hydrothermal etching process. These fabricated titanium surfaces were shown to possess selective bactericidal activity, eliminating almost 50% of Pseudomonas aeruginosa cells and about 20% of the Staphylococcus aureus cells coming into contact with the surface. These nano-patterned surfaces were also shown to enhance the aligned attachment behavior and proliferation of primary human fibroblasts over 10 days of growth. These antibacterial surfaces, which are capable of exhibiting differential responses to bacterial and eukaryotic cells, represent surfaces that have excellent prospects for biomedical applications. PMID:26576662

Forging difference out of similarity: the multiplicity of corrective experience.

PubMed

Hoffman, Irwin Z

2006-07-01

In the context of work with an adult survivor of childhood sexual abuse, the interplay of multiple forms of engagement contributing to therapeutic action is explored. The compulsion to repeat old patterns is seen to be gradually overcome by new corrective experience in which the whole of the patient's sense of the analyst as a person is greater than the sum of its parts. Interpretation of enactments--often involving patterns of dominance and submission--is complemented by a range of "helpful" actions that must be detoxified. That process entails the progressive differentiation of coercion and influence, on the one hand, and of compliance and responsiveness, on the other In the end, autonomy and creative responsiveness emerge as integral to each other rather than as mutually exclusive. This development requires that the patient gradually relinquish an "essentialist" view of self and other in favor of a "constructivist" view, in which the ambiguity of experience offers opportunities for new forms of relational engagement and understanding.

Effects of mannose-binding lectin on pulmonary gene expression and innate immune inflammatory response to ozone

PubMed Central

Ciencewicki, Jonathan M.; Verhein, Kirsten C.; Gerrish, Kevin; McCaw, Zachary R.; Li, Jianying; Bushel, Pierre R.

2016-01-01

Ozone is a common, potent oxidant pollutant in industrialized nations. Ozone exposure causes airway hyperreactivity, lung hyperpermeability, inflammation, and cell damage in humans and laboratory animals, and exposure to ozone has been associated with exacerbation of asthma, altered lung function, and mortality. The mechanisms of ozone-induced lung injury and differential susceptibility are not fully understood. Ozone-induced lung inflammation is mediated, in part, by the innate immune system. We hypothesized that mannose-binding lectin (MBL), an innate immunity serum protein, contributes to the proinflammatory events caused by ozone-mediated activation of the innate immune system. Wild-type (Mbl+/+) and MBL-deficient (Mbl−/−) mice were exposed to ozone (0.3 ppm) for up to 72 h, and bronchoalveolar lavage fluid was examined for inflammatory markers. Mean numbers of eosinophils and neutrophils and levels of the neutrophil attractants C-X-C motif chemokines 2 [Cxcl2 (major intrinsic protein 2)] and 5 [Cxcl5 (limb expression, LIX)] in the bronchoalveolar lavage fluid were significantly lower in Mbl−/− than Mbl+/+ mice exposed to ozone. Using genome-wide mRNA microarray analyses, we identified significant differences in transcript response profiles and networks at baseline [e.g., nuclear factor erythroid-related factor 2 (NRF2)-mediated oxidative stress response] and after exposure (e.g., humoral immune response) between Mbl+/+ and Mbl−/− mice. The microarray data were further analyzed to discover several informative differential response patterns and subsequent gene sets, including the antimicrobial response and the inflammatory response. We also used the lists of gene transcripts to search the LINCS L1000CDS2 data sets to identify agents that are predicted to perturb ozone-induced changes in gene transcripts and inflammation. These novel findings demonstrate that targeted deletion of Mbl caused differential levels of inflammation-related gene sets at baseline and after exposure to ozone and significantly reduced pulmonary inflammation, thus indicating an important innate immunomodulatory role of the gene in this model. PMID:27106289

Transcriptomic Profiling during the Post-Harvest of Heat-Treated Dixiland Prunus persica Fruits: Common and Distinct Response to Heat and Cold

PubMed Central

Lauxmann, Martin A.; Brun, Bianca; Borsani, Julia; Bustamante, Claudia A.; Budde, Claudio O.; Lara, María V.; Drincovich, María F.

2012-01-01

Cold storage is extensively used to slow the rapid deterioration of peach (Prunus persica L. Batsch) fruit after harvest. However, peach fruit subjected to long periods of cold storage develop chilling injury (CI) symptoms. Post-harvest heat treatment (HT) of peach fruit prior to cold storage is effective in reducing some CI symptoms, maintaining fruit quality, preventing softening and controlling post-harvest diseases. To identify the molecular changes induced by HT, which may be associated to CI protection, the differential transcriptome of peach fruit subjected to HT was characterized by the differential display technique. A total of 127 differentially expressed unigenes (DEUs), with a presence-absence pattern, were identified comparing peach fruit ripening at 20°C with those exposed to a 39°C-HT for 3 days. The 127 DEUs were divided into four expression profile clusters, among which the heat-induced (47%) and heat-repressed (36%) groups resulted the most represented, including genes with unknown function, or involved in protein modification, transcription or RNA metabolism. Considering the CI-protection induced by HT, 23-heat-responsive genes were selected and analyzed during and after short-term cold storage of peach fruit. More than 90% of the genes selected resulted modified by cold, from which nearly 60% followed the same and nearly 40% opposite response to heat and cold. Moreover, by using available Arabidopsis microarray data, it was found that nearly 70% of the peach-heat responsive genes also respond to cold in Arabidopsis, either following the same trend or showing an opposite response. Overall, the high number of common responsive genes to heat and cold identified in the present work indicates that HT of peach fruit after harvest induces a cold response involving complex cellular processes; identifying genes that are involved in the better preparation of peach fruit for cold-storage and unraveling the basis for the CI protection induced by HT. PMID:23236430

Dehydration-responsive miRNAs in foxtail millet: genome-wide identification, characterization and expression profiling.

PubMed

Yadav, Amita; Khan, Yusuf; Prasad, Manoj

2016-03-01

A set of novel and known dehydration-responsive miRNAs have been identified in foxtail millet. These findings provide new insights into understanding the functional role of miRNAs and their respective targets in regulating plant response to dehydration stress. MicroRNAs perform significant regulatory roles in growth, development and stress response of plants. Though the miRNA-mediated gene regulatory networks under dehydration stress remain largely unexplored in plant including foxtail millet (Setaria italica), which is a natural abiotic stress tolerant crop. To find out the dehydration-responsive miRNAs at the global level, four small RNA libraries were constructed from control and dehydration stress treated seedlings of two foxtail millet cultivars showing contrasting tolerance behavior towards dehydration stress. Using Illumina sequencing technology, 55 known and 136 novel miRNAs were identified, representing 22 and 48 miRNA families, respectively. Eighteen known and 33 novel miRNAs were differentially expressed during dehydration stress. After the stress treatment, 32 dehydration-responsive miRNAs were up-regulated in tolerant cultivar and 22 miRNAs were down-regulated in sensitive cultivar, suggesting that miRNA-mediated molecular regulation might play important roles in providing contrasting characteristics to these cultivars. Predicted targets of identified miRNAs were found to encode various transcription factors and functional enzymes, indicating their involvement in broad spectrum regulatory functions and biological processes. Further, differential expression patterns of seven known miRNAs were validated by northern blot and expression of ten novel dehydration-responsive miRNAs were confirmed by SL-qRT PCR. Differential expression behavior of five miRNA-target genes was verified under dehydration stress treatment and two of them also validated by RLM RACE. Overall, the present study highlights the importance of dehydration stress-associated post-transcriptional regulation governed by miRNAs and their targets in a naturally stress-tolerant model crop.

De Novo Transcriptional Analysis of Alfalfa in Response to Saline-Alkaline Stress.

PubMed

An, Yi-Min; Song, Li-Li; Liu, Ying-Rui; Shu, Yong-Jun; Guo, Chang-Hong

2016-01-01

Saline-alkaline stress, caused by high levels of harmful carbonate salts and high soil pH, is a major abiotic stress that affects crop productivity. Alfalfa is a widely cultivated perennial forage legume with some tolerance to biotic and abiotic stresses, especially to saline-alkaline stress. To elucidate the mechanism underlying plant saline-alkaline tolerance, we conducted transcriptome analysis of whole alfalfa seedlings treated with saline-alkaline solutions for 0 day (control), 1 day (short-term treatment), and 7 days (long-term treatment) using ion torrent sequencing technology. A transcriptome database dataset of 53,853 unigenes was generated, and 2,286 and 2,233 genes were differentially expressed in the short-term and long-term treatment, respectively. Gene ontology analysis revealed 14 highly enriched pathways and demonstrated the differential response of metabolic pathways between the short-term and long-term treatment. The expression levels of 109 and 96 transcription factors were significantly altered significantly after 1 day and 7 days of treatment, respectively. Specific responses of peroxidase, flavonoids, and the light pathway component indicated that the antioxidant capacity was one of the central mechanisms of saline-alkaline stress tolerance response in alfalfa. Among the 18 differentially expressed genes examined by real time PCR, the expression levels of eight genes, including inositol transporter, DNA binding protein, raffinose synthase, ferritin, aldo/keto reductase, glutathione S-transferase, xyloglucan endotrans glucosylase, and a NAC transcription factor, exhibited different patterns in response to saline and alkaline stress. The expression levels of the NAC transcription factor and glutathione S-transferase were altered significantly under saline stress and saline-alkaline stress; they were upregulated under saline-alkaline stress and downregulated under salt stress. Physiology assays showed an increased concentration of reactive oxygen species and malondialdehyde and a decreased content of chlorophyll, indicating that anti-oxidation and detoxification play an important role in response to saline-alkaline stress. Overall, the transcriptome analysis provided novel insights into the saline-alkaline stress tolerance response mechanisms in alfalfa.

De Novo Transcriptional Analysis of Alfalfa in Response to Saline-Alkaline Stress

PubMed Central

An, Yi-Min; Song, Li-Li; Liu, Ying-Rui; Shu, Yong-Jun; Guo, Chang-Hong

2016-01-01

Saline-alkaline stress, caused by high levels of harmful carbonate salts and high soil pH, is a major abiotic stress that affects crop productivity. Alfalfa is a widely cultivated perennial forage legume with some tolerance to biotic and abiotic stresses, especially to saline-alkaline stress. To elucidate the mechanism underlying plant saline-alkaline tolerance, we conducted transcriptome analysis of whole alfalfa seedlings treated with saline-alkaline solutions for 0 day (control), 1 day (short-term treatment), and 7 days (long-term treatment) using ion torrent sequencing technology. A transcriptome database dataset of 53,853 unigenes was generated, and 2,286 and 2,233 genes were differentially expressed in the short-term and long-term treatment, respectively. Gene ontology analysis revealed 14 highly enriched pathways and demonstrated the differential response of metabolic pathways between the short-term and long-term treatment. The expression levels of 109 and 96 transcription factors were significantly altered significantly after 1 day and 7 days of treatment, respectively. Specific responses of peroxidase, flavonoids, and the light pathway component indicated that the antioxidant capacity was one of the central mechanisms of saline-alkaline stress tolerance response in alfalfa. Among the 18 differentially expressed genes examined by real time PCR, the expression levels of eight genes, including inositol transporter, DNA binding protein, raffinose synthase, ferritin, aldo/keto reductase, glutathione S-transferase, xyloglucan endotrans glucosylase, and a NAC transcription factor, exhibited different patterns in response to saline and alkaline stress. The expression levels of the NAC transcription factor and glutathione S-transferase were altered significantly under saline stress and saline-alkaline stress; they were upregulated under saline-alkaline stress and downregulated under salt stress. Physiology assays showed an increased concentration of reactive oxygen species and malondialdehyde and a decreased content of chlorophyll, indicating that anti-oxidation and detoxification play an important role in response to saline-alkaline stress. Overall, the transcriptome analysis provided novel insights into the saline-alkaline stress tolerance response mechanisms in alfalfa. PMID:27458463

Identification and molecular characterization of a trans-acting small interfering RNA producing locus regulating leaf rust responsive gene expression in wheat (Triticum aestivum L.).

PubMed

Dutta, Summi; Kumar, Dhananjay; Jha, Shailendra; Prabhu, Kumble Vinod; Kumar, Manish; Mukhopadhyay, Kunal

2017-11-01

A novel leaf rust responsive ta-siRNA-producing locus was identified in wheat showing similarity to 28S rRNA and generated four differentially expressing ta-siRNAs by phasing which targeted stress responsive genes. Trans-acting-small interfering RNAs (Ta-siRNAs) are plant specific molecules generally involved in development and are also stress responsive. Ta-siRNAs identified in wheat till date are all responsive to abiotic stress only. Wheat cultivation is severely affected by rusts and leaf rust particularly affects grain filling. This study reports a novel ta-siRNA producing locus (TAS) in wheat which is a segment of 28S ribosomal RNA but shows differential expression during leaf rust infestation. Four small RNA libraries prepared from wheat Near Isogenic Lines were treated with leaf rust pathogen and compared with untreated controls. A TAS with the ability to generate four ta-siRNAs by phasing events was identified along with the microRNA TamiR16 as the phase initiator. The targets of the ta-siRNAs included α-gliadin, leucine rich repeat, trans-membrane proteins, glutathione-S-transferase, and fatty acid desaturase among others, which are either stress responsive genes or are essential for normal growth and development of plants. Expression of the TAS, its generated ta-siRNAs, and their target genes were profiled at five different time points after pathogen inoculation of susceptible and resistant wheat isolines and compared with mock-inoculated controls. Comparative analysis of expression unveiled differential and reciprocal relationship as well as discrete patterns between susceptible and resistant isolines. The expression profiles of the target genes of the identified ta-siRNAs advocate more towards effector triggered susceptibility favouring pathogenesis. The study helps in discerning the functions of wheat genes regulated by ta-siRNAs in response to leaf rust.

Differential subnetwork of chemokines/cytokines in human, mouse, and rat brain cells after oxygen-glucose deprivation.

PubMed

Du, Yang; Deng, Wenjun; Wang, Zixing; Ning, MingMing; Zhang, Wei; Zhou, Yiming; Lo, Eng H; Xing, Changhong

2017-04-01

Mice and rats are the most commonly used animals for preclinical stroke studies, but it is unclear whether targets and mechanisms are always the same across different species. Here, we mapped the baseline expression of a chemokine/cytokine subnetwork and compared responses after oxygen-glucose deprivation in primary neurons, astrocytes, and microglia from mouse, rat, and human. Baseline profiles of chemokines (CX3CL1, CXCL12, CCL2, CCL3, and CXCL10) and cytokines (IL-1α, IL-1β, IL-6, IL-10, and TNFα) showed significant differences between human and rodents. The response of chemokines/cytokines to oxygen-glucose deprivation was also significantly different between species. After 4 h oxygen-glucose deprivation and 4 h reoxygenation, human and rat neurons showed similar changes with a downregulation in many chemokines, whereas mouse neurons showed a mixed response with up- and down-regulated genes. For astrocytes, subnetwork response patterns were more similar in rats and mice compared to humans. For microglia, rat cells showed an upregulation in all chemokines/cytokines, mouse cells had many down-regulated genes, and human cells showed a mixed response with up- and down-regulated genes. This study provides proof-of-concept that species differences exist in chemokine/cytokine subnetworks in brain cells that may be relevant to stroke pathophysiology. Further investigation of differential gene pathways across species is warranted.

Transcriptomic and Proteomic Analyses Reveal Key Innate Immune Signatures in the Host Response to the Gastrointestinal Pathogen Campylobacter concisus

PubMed Central

Deshpande, Nandan P.; Man, Si Ming; Burgos-Portugal, Jose A.; Khattak, Faisal A.; Raftery, Mark J.; Wilkins, Marc R.; Mitchell, Hazel M.

2014-01-01

Pathogenic species within the genus Campylobacter are responsible for a considerable burden on global health. Campylobacter concisus is an emergent pathogen that plays a role in acute and chronic gastrointestinal disease. Despite ongoing research on Campylobacter virulence mechanisms, little is known regarding the immunological profile of the host response to Campylobacter infection. In this study, we describe a comprehensive global profile of innate immune responses to C. concisus infection in differentiated THP-1 macrophages infected with an adherent and invasive strain of C. concisus. Using RNA sequencing (RNA-seq), quantitative PCR (qPCR), mass spectrometry, and confocal microscopy, we observed differential expression of pattern recognition receptors and robust upregulation of DNA- and RNA-sensing molecules. In particular, we observed IFI16 inflammasome assembly in C. concisus-infected macrophages. Global profiling of the transcriptome revealed the significant regulation of a total of 8,343 transcripts upon infection with C. concisus, which included the activation of key inflammatory pathways involving CREB1, NF-κB, STAT, and interferon regulatory factor signaling. Thirteen microRNAs and 333 noncoding RNAs were significantly regulated upon infection, including MIR221, which has been associated with colorectal carcinogenesis. This study represents a major advance in our understanding of host recognition and innate immune responses to infection by C. concisus. PMID:25486993

Insights into the species-specific TLR4 signaling mechanism in response to Rhodobacter sphaeroides lipid A detection

NASA Astrophysics Data System (ADS)

Anwar, Muhammad Ayaz; Panneerselvam, Suresh; Shah, Masaud; Choi, Sangdun

2015-01-01

TLR4 in complex with MD2 senses the presence of lipid A (LA) and initiates a signaling cascade that curb the infection. This complex is evolutionarily conserved and can initiate the immune system in response to a variety of LAs. In this study, molecular dynamics simulation (25 ns) was performed to elucidate the differential behavior of TLR4/MD2 complex in response to Rhodobacter sphaeroides lipid A (RsLA). Penta-acyl chain-containing RsLA is at the verge of agonist (6 acyl-chains) and antagonist (4 acyl-chains) structure, and activates the TLR4 pathway in horses and hamsters, while inhibiting in humans and murine. In the time-evolved coordinates, the promising factors that dictated the differential response included the local and global mobility pattern of complexes, solvent-accessible surface area of ligand, and surface charge distributions of TLR4 and MD2. We showed that the GlcN1-GlcN2 backbone acquires agonist (3FXI)-like configurations in horses and hamsters, while acquiring antagonist (2E59)-like configurations in humans and murine systems. Moreover, analysis of F126 behavior in the MD2 F126 loop (amino acids 123-129) and loop EF (81-89) suggested that certain sequence variations also contribute to species-specific response. This study underlines the TLR4 signaling mechanism and provides new therapeutic opportunities.

Type I interferon dependence of plasmacytoid dendritic cell activation and migration

PubMed Central

Asselin-Paturel, Carine; Brizard, Géraldine; Chemin, Karine; Boonstra, Andre; O'Garra, Anne; Vicari, Alain; Trinchieri, Giorgio

2005-01-01

Differential expression of Toll-like receptor (TLR) by conventional dendritic cells (cDCs) and plasmacytoid DC (pDCs) has been suggested to influence the type of immune response induced by microbial pathogens. In this study we show that, in vivo, cDCs and pDCs are equally activated by TLR4, -7, and -9 ligands. Type I interferon (IFN) was important for pDC activation in vivo in response to all three TLR ligands, whereas cDCs required type I IFN signaling only for TLR9- and partially for TLR7-mediated activation. Although TLR ligands induced in situ migration of spleen cDC into the T cell area, spleen pDCs formed clusters in the marginal zone and in the outer T cell area 6 h after injection of TLR9 and TLR7 ligands, respectively. In vivo treatment with TLR9 ligands decreased pDC ability to migrate ex vivo in response to IFN-induced CXCR3 ligands and increased their response to CCR7 ligands. Unlike cDCs, the migration pattern of pDCs required type I IFN for induction of CXCR3 ligands and responsiveness to CCR7 ligands. These data demonstrate that mouse pDCs differ from cDCs in the in vivo response to TLR ligands, in terms of pattern and type I IFN requirement for activation and migration. PMID:15795237

Diffractive Optical Analysis for Refractive Index Sensing using Transparent Phase Gratings

PubMed Central

Kumawat, Nityanand; Pal, Parama; Varma, Manoj

2015-01-01

We report the implementation of a micro-patterned, glass-based photonic sensing element that is capable of label-free biosensing. The diffractive optical analyzer is based on the differential response of diffracted orders to bulk as well as surface refractive index changes. The differential read-out suppresses signal drifts and enables time-resolved determination of refractive index changes in the sample cell. A remarkable feature of this device is that under appropriate conditions, the measurement sensitivity of the sensor can be enhanced by more than two orders of magnitude due to interference between multiply reflected diffracted orders. A noise-equivalent limit of detection (LoD) of 6 × 10−7 was achieved with this technique with scope for further improvement. PMID:26578408

Unbiased phosphoproteomic method identifies the initial effects of a methacrylic acid copolymer on macrophages

PubMed Central

Chamberlain, Michael Dean; Wells, Laura A.; Lisovsky, Alexandra; Guo, Hongbo; Isserlin, Ruth; Talior-Volodarsky, Ilana; Mahou, Redouan; Emili, Andrew; Sefton, Michael V.

2015-01-01

An unbiased phosphoproteomic method was used to identify biomaterial-associated changes in the phosphorylation patterns of macrophage-like cells. The phosphorylation differences between differentiated THP1 (dTHP1) cells treated for 10, 20, or 30 min with a vascular regenerative methacrylic acid (MAA) copolymer or a control methyl methacrylate (MM) copolymer were determined by MS. There were 1,470 peptides (corresponding to 729 proteins) that were differentially phosphorylated in dTHP1 cells treated with the two materials with a greater cellular response to MAA treatment. In addition to identifying pathways (such as integrin signaling and cytoskeletal arrangement) that are well known to change with cell–material interaction, previously unidentified pathways, such as apoptosis and mRNA splicing, were also discovered. PMID:26261332

The kidney in the pathogenesis of hypertension: the role of renal nerves.

PubMed

DiBona, G F

1985-04-01

The intrinsic efferent innervation of the kidney consists of exclusively noradrenergic fibers that innervate the preglomerular and postgomerular vasculature, all elements of the juxtagomerular apparatus and virtually all segments of the nephron in both cortical and medullo-papillary regions. Increases in efferent renal sympathetic nerve activity produce renal vasoconstriction, release of renin, catecholamines, prostaglandins and other vasoactive substances, and increases in renal tubular sodium reabsorption; these responses are graded and differentiated. The intrinsic afferent innervation of the kidney consists of mechanoreceptors and chemoreceptors which participate in reno-renal and reno-systemic reflexes that modulate sympathetic neural outflow in an organ-specific differentiated pattern. Therefore, alterations in efferent and afferent renal nerve activity produce changes in several important renal functions known to contribute to the development and maintenance of hypertension.

Characterization of Alcohol-induced Filamentous Growth in Saccharomyces cerevisiae

PubMed Central

Lorenz, Michael C.; Cutler, N. Shane; Heitman, Joseph

2000-01-01

Diploid cells of the budding yeast Saccharomyces cerevisiae starved for nitrogen differentiate into a filamentous growth form. Poor carbon sources such as starches can also stimulate filamentation, whereas haploid cells undergo a similar invasive growth response in rich medium. Previous work has demonstrated a role for various alcohols, by-products of amino acid metabolism, in altering cellular morphology. We found that several alcohols, notably isoamyl alcohol and 1-butanol, stimulate filamentous growth in haploid cells in which this differentiation is normally repressed. Butanol also induces cell elongation and changes in budding pattern, leading to a pseudohyphal morphology, even in liquid medium. The filamentous colony morphology and cell elongation require elements of the pheromone-responsive MAPK cascade and TEC1, whereas components of the nutrient-sensing machinery, such as MEP2, GPA2, and GPR1, do not affect this phenomenon. A screen for 1-butanol–insensitive mutants identified additional proteins that regulate polarized growth (BUD8, BEM1, BEM4, and FIG1), mitochondrial function (MSM1, MRP21, and HMI1), and a transcriptional regulator (CHD1). Furthermore, we have also found that ethanol stimulates hyperfilamentation in diploid cells, again in a MAPK-dependent manner. Together, these results suggest that yeast may sense a combination of nutrient limitation and metabolic by-products to regulate differentiation. PMID:10637301

Haploid parthenotes express differential response to in vitro exposure of ammonia compared to normally fertilized embryos.

PubMed

Nair, Ramya; Mutalik, Srinivas; Dasappa, Jagadeesh Prasad; Kalthur, Guruprasad; Adiga, Satish Kumar

2017-04-22

In the present study, we assessed whether absence of paternal genome imparts any differential response in embryos to chemical stress such as ammonia. Parthenogenesis was induced in MII stage oocytes using 10 mM SrCl 2 in M16 medium. Parthenotes and normally fertilized embryos at 2 cell stage were exposed to different concentrations of ammonia and cultured till blastocyst. Exposure of ammonia to normally fertilized embryos resulted in significant decrease in the developmental potential (p < 0.0001) and blastocyst quality (p < 0.001). Whereas, in parthenotes, even though lower concentrations of ammonia did not have any effect, at 200 μM concentration the blastocyst rate was two times higher than control. The baseline apoptotic index was higher in parthenotes compared to normally fertilized embryos, which further increased after ammonium exposure (p < 0.001). Unlike in normally fertilized embryos ammonia exposure altered the mitochondrial distribution pattern and lead to increased expression of Oct4, Nanog and Na + /K + ion exchange channel, while the cytochrome C expression was downregulated. This indicates that haploidy and/or absence of paternal factors in the embryo results in differential tolerance to stress induced by ammonia. Copyright © 2017 Elsevier Inc. All rights reserved.

RNA sequencing provides exquisite insight into the manipulation of the alveolar macrophage by tubercle bacilli.

PubMed

Nalpas, Nicolas C; Magee, David A; Conlon, Kevin M; Browne, John A; Healy, Claire; McLoughlin, Kirsten E; Rue-Albrecht, Kévin; McGettigan, Paul A; Killick, Kate E; Gormley, Eamonn; Gordon, Stephen V; MacHugh, David E

2015-09-08

Mycobacterium bovis, the agent of bovine tuberculosis, causes an estimated $3 billion annual losses to global agriculture due, in part, to the limitations of current diagnostics. Development of next-generation diagnostics requires a greater understanding of the interaction between the pathogen and the bovine host. Therefore, to explore the early response of the alveolar macrophage to infection, we report the first application of RNA-sequencing to define, in exquisite detail, the transcriptomes of M. bovis-infected and non-infected alveolar macrophages from ten calves at 2, 6, 24 and 48 hours post-infection. Differentially expressed sense genes were detected at these time points that revealed enrichment of innate immune signalling functions, and transcriptional suppression of host defence mechanisms (e.g., lysosome maturation). We also detected differentially expressed natural antisense transcripts, which may play a role in subverting innate immune mechanisms following infection. Furthermore, we report differential expression of novel bovine genes, some of which have immune-related functions based on orthology with human proteins. This is the first in-depth transcriptomics investigation of the alveolar macrophage response to the early stages of M. bovis infection and reveals complex patterns of gene expression and regulation that underlie the immunomodulatory mechanisms used by M. bovis to evade host defence mechanisms.

Exercise training alters DNA methylation patterns in genes related to muscle growth and differentiation in mice.

PubMed

Kanzleiter, Timo; Jähnert, Markus; Schulze, Gunnar; Selbig, Joachim; Hallahan, Nicole; Schwenk, Robert Wolfgang; Schürmann, Annette

2015-05-15

The adaptive response of skeletal muscle to exercise training is tightly controlled and therefore requires transcriptional regulation. DNA methylation is an epigenetic mechanism known to modulate gene expression, but its contribution to exercise-induced adaptations in skeletal muscle is not well studied. Here, we describe a genome-wide analysis of DNA methylation in muscle of trained mice (n = 3). Compared with sedentary controls, 2,762 genes exhibited differentially methylated CpGs (P < 0.05, meth diff >5%, coverage >10) in their putative promoter regions. Alignment with gene expression data (n = 6) revealed 200 genes with a negative correlation between methylation and expression changes in response to exercise training. The majority of these genes were related to muscle growth and differentiation, and a minor fraction involved in metabolic regulation. Among the candidates were genes that regulate the expression of myogenic regulatory factors (Plexin A2) as well as genes that participate in muscle hypertrophy (Igfbp4) and motor neuron innervation (Dok7). Interestingly, a transcription factor binding site enrichment study discovered significantly enriched occurrence of CpG methylation in the binding sites of the myogenic regulatory factors MyoD and myogenin. These findings suggest that DNA methylation is involved in the regulation of muscle adaptation to regular exercise training. Copyright © 2015 the American Physiological Society.

Sex-specific variation in signaling pathways and gene expression patterns in human leukocytes in response to endotoxin and exercise.

PubMed

Abbasi, Asghar; de Paula Vieira, Rodolfo; Bischof, Felix; Walter, Michael; Movassaghi, Masoud; Berchtold, Nicole C; Niess, Andreas M; Cotman, Carl W; Northoff, Hinnak

2016-11-10

While exercise effects on the immune system have received increasing attention in recent years, it remains unclear to what extent gender and fluctuations in sex hormones during menstrual cycle influence immunological responses to exercise. We investigated mRNA changes induced through exhaustive exercise (half-marathon; pre-exercise and post-exercise [30 min, 3 h, 24 h] on whole blood cultures ± lipopolysaccharide [LPS] [1 h]) with a specific focus on sex differences (men vs women in luteal phase) as an extension of our previous study. Inflammation related signaling pathways, TLRs, cytosolic DNA sensing and RIG-I like receptors were differentially activated between sexes in LPS-stimulated cultures. Genes differentially regulated between sexes included TNIP-1, TNIP-3, IL-6, HIVEP1, CXCL3, CCR3, IL-8, and CD69, revealing a bias towards less anti-inflammatory gene regulation in women compared to men. In addition, several genes relevant to brain function (KMO, DDIT4, VEGFA, IGF1R, IGF2R, and FGD4) showed differential activation between sexes. Some of these genes (e.g., KMO in women, DDIT4 in both sexes) potentially constitute neuroprotective mechanisms. These data reveal that the exercise-induced change in gene expression might be gender and menstrual cycle phase dependent.

A DN-mda5 transgenic zebrafish model demonstrates that Mda5 plays an important role in snakehead rhabdovirus resistance.

PubMed

Gabor, K A; Charette, J R; Pietraszewski, M J; Wingfield, D J; Shim, J S; Millard, P J; Kim, C H

2015-08-01

Melanoma Differentiation-Associated protein 5 (MDA5) is a member of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, which is a cytosolic pattern recognition receptor that detects viral nucleic acids. Here we show an Mda5-dependent response to rhabdovirus infection in vivo using a dominant-negative mda5 transgenic zebrafish. Dominant-negative mda5 zebrafish embryos displayed an impaired antiviral immune response compared to wild-type counterparts that can be rescued by recombinant full-length Mda5. To our knowledge, we have generated the first dominant-negative mda5 transgenic zebrafish and demonstrated a critical role for Mda5 in the antiviral response to rhabdovirus. Copyright © 2015 Elsevier Ltd. All rights reserved.

RNA-Seq Reveals an Integrated Immune Response in Nucleated Erythrocytes

PubMed Central

Morera, Davinia; Roher, Nerea; Ribas, Laia; Balasch, Joan Carles; Doñate, Carmen; Callol, Agnes; Boltaña, Sebastian; Roberts, Steven; Goetz, Giles; Goetz, Frederick W.; MacKenzie, Simon A.

2011-01-01

Background Throughout the primary literature and within textbooks, the erythrocyte has been tacitly accepted to have maintained a unique physiological role; namely gas transport and exchange. In non-mammalian vertebrates, nucleated erythrocytes are present in circulation throughout the life cycle and a fragmented series of observations in mammals support a potential role in non-respiratory biological processes. We hypothesised that nucleated erythrocytes could actively participate via ligand-induced transcriptional re-programming in the immune response. Methodology/Principal Findings Nucleated erythrocytes from both fish and birds express and regulate specific pattern recognition receptor (PRR) mRNAs and, thus, are capable of specific pathogen associated molecular pattern (PAMP) detection that is central to the innate immune response. In vitro challenge with diverse PAMPs led to de novo specific mRNA synthesis of both receptors and response factors including interferon-alpha (IFNα) that exhibit a stimulus-specific polysomal shift supporting active translation. RNA-Seq analysis of the PAMP (Poly (I∶C), polyinosinic∶polycytidylic acid)-erythrocyte response uncovered diverse cohorts of differentially expressed mRNA transcripts related to multiple physiological systems including the endocrine, reproductive and immune. Moreover, erythrocyte-derived conditioned mediums induced a type-1 interferon response in macrophages thus supporting an integrative role for the erythrocytes in the immune response. Conclusions/Significance We demonstrate that nucleated erythrocytes in non-mammalian vertebrates spanning significant phylogenetic distance participate in the immune response. RNA-Seq studies highlight a mRNA repertoire that suggests a previously unrecognized integrative role for the erythrocytes in other physiological systems. PMID:22046430

Differential gene expression profiles in neurons generated from lymphoblastoid B-cell line-derived iPS cells from monozygotic twin cases with treatment-resistant schizophrenia and discordant responses to clozapine.

PubMed

Nakazawa, Takanobu; Kikuchi, Masataka; Ishikawa, Mitsuru; Yamamori, Hidenaga; Nagayasu, Kazuki; Matsumoto, Takuya; Fujimoto, Michiko; Yasuda, Yuka; Fujiwara, Mikiya; Okada, Shota; Matsumura, Kensuke; Kasai, Atsushi; Hayata-Takano, Atsuko; Shintani, Norihito; Numata, Shusuke; Takuma, Kazuhiro; Akamatsu, Wado; Okano, Hideyuki; Nakaya, Akihiro; Hashimoto, Hitoshi; Hashimoto, Ryota

2017-03-01

Schizophrenia is a chronic psychiatric disorder with complex genetic and environmental origins. While many antipsychotics have been demonstrated as effective in the treatment of schizophrenia, a substantial number of schizophrenia patients are partially or fully unresponsive to the treatment. Clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia; however, clozapine has rare but serious side-effects. Furthermore, there is inter-individual variability in the drug response to clozapine treatment. Therefore, the identification of the molecular mechanisms underlying the action of clozapine and drug response predictors is imperative. In the present study, we focused on a pair of monozygotic twin cases with treatment-resistant schizophrenia, in which one twin responded well to clozapine treatment and the other twin did not. Using induced pluripotent stem (iPS) cell-based technology, we generated neurons from iPS cells derived from these patients and subsequently performed RNA-sequencing to compare the transcriptome profiles of the mock or clozapine-treated neurons. Although, these iPS cells similarly differentiated into neurons, several genes encoding homophilic cell adhesion molecules, such as protocadherin genes, showed differential expression patterns between these two patients. These results, which contribute to the current understanding of the molecular mechanisms of clozapine action, establish a new strategy for the use of monozygotic twin studies in schizophrenia research. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Apolipoprotein E modifies the CNS response to injury via a histamine-mediated pathway.

PubMed

Mace, Brian E; Wang, Haichen; Lynch, John R; Moss, Jason; Sullivan, Patrick; Colton, Heidi; Morgan, Kevin; Renauld, Jean-Christophe; Laskowitz, Daniel T

2007-04-01

Recent evidence demonstrates that apolipoprotein E (apoE) influences the central nervous system (CNS) response to both acute and chronic injury. To address the mechanisms by which apoE influences neurological disease, we examined differential gene expression in the brains of apoE transgenic mice after closed head injury. Apart from confirming the knockout of apoE, the largest differential gene expression occurred for the interleukin-9 receptor (IL-9R), which was > 100-fold up-regulated in apoE-deficient versus wild-type mice. We observed a similar pattern of posttraumatic IL-9R up-regulation in APOE4 targeted replacement mice as compared with their APOE3 counterparts. This difference in gene expression was associated with increased neuronal protein expression of IL-9R in E4 animals compared with E3 as demonstrated by immunohistochemistry. The consequence of IL-9R binding in mast cells is the induction of proliferation and differentiation. This indirectly favors degranulation and release of histamine and inflammatory mediators, which have previously been demonstrated to exacerbate secondary neuronal injury. We found that apoE-deficient animals had increased levels of systemic histamine after injury and that pre-treatment with antihistamines improved functional outcomes in apoE-deficient but not wild-type animals after head injury. These results suggest that apoE modifies secondary neuronal injury caused by histamine release and are consistent with previous observations that apoE affects the CNS inflammatory response in an isoform-specific manner.

Enhanced osteogenic differentiation of MC3T3-E1 cells on grid-topographic surface and evidence for involvement of YAP mediator.

PubMed

Zhang, Yingying; Gong, He; Sun, Yan; Huang, Yan; Fan, Yubo

2016-05-01

Numerous studies have shown that surface topography can promote cell-substrate associations and deeply influence cell fate. The intracellular mechanism or how micro- or nano-patterned extracellular signal is ultimately linked to activity of nuclear transcription factors remains unknown. It has been reported that Yes-associated protein (YAP) can respond to extracellular matrix microenvironment signals, thus regulates stem cell differentiation process. We propose that YAP may play a role in mediating the topography induced cell differentiation. To this end, we fabricated polydimethylsiloxane (PDMS) micropatterns with grid topology (GT) (3 μm pattern width, 2 μm pattern interval length, 7 μm pattern height); nonpatterned PDMS substrates were used as the planar controls. The MC3T3-E1 cells were then cultured on these surfaces, respectively, in osteogenic inducing medium. Cell differentiation in terms of osteogenesis related gene expression, protein levels, alkaline phosphatase activity and extracellular matrix mineralization was assessed. It was shown that the cells on GT surfaces had stronger osteogenesis capacity. In addition, expression level of YAP was increased when MC3T3-E1 cells grew on GT substrates, which was similar to the levels of osteogenic differentiation markers. It was also shown that YAP knockdown attenuated GT substrates-induced MC3T3-E1 differentiation, which reduced the osteogenic differentiation effect of the GT substrates. Collectively, our findings indicate that GT substrates-induced MC3T3-E1 differentiation may be associated with YAP. This paper provides new target points for transcriptional mechanism research of microenvironment induced cell differentiation and a useful approach to obtain more biofunctionalization scaffolds for tissue engineering. © 2016 Wiley Periodicals, Inc.

Pharmacoepigenomic responses of antipsychotic drugs on pharmacogenes are likely to be modulated by miRNAs.

PubMed

Swathy, Babu; Saradalekshmi, Koramannil R; Nair, Indu V; Nair, Chandrasekharan; Banerjee, Moinak

2017-06-01

It is imperative to differentiate the role of host epigenetics from pharmacoepigenetics in resolving therapeutic response. Therefore, the objective was to identify how antipsychotic drugs influence epigenetic response on pharmacogenes. The study design was based on in vitro evaluation of pharmacoepigenetic response of haloperidol, clozapine and olanzapine. Post antipsychotic treatment, the alterations in expression of ABCB1, CYP1A2 and CYP3A4 were monitored, and followed up by promoter methylation and their target miRNA expression studies. Critical observations were followed up in a restrictive clinical setting. Under in vitro conditions increased expression of ABCB1, CYP1A2 and CYP3A4 was observed which seems to be regulated by miR-27a and miR-128a and not by methylation. A similar pattern was observed in clinical setting with ABCB1, which was reflective of good therapeutic response. The study demonstrates that antipsychotic drugs can influence miRNA-mediated epigenetic response in pharmacogenes resulting in modulating therapeutic response.

Wrinkling pattern evolution of cylindrical biological tissues with differential growth.

PubMed

Jia, Fei; Li, Bo; Cao, Yan-Ping; Xie, Wei-Hua; Feng, Xi-Qiao

2015-01-01

Three-dimensional surface wrinkling of soft cylindrical tissues induced by differential growth is explored. Differential volumetric growth can cause their morphological stability, leading to the formation of hexagonal and labyrinth wrinkles. During postbuckling, multiple bifurcations and morphological transitions may occur as a consequence of continuous growth in the surface layer. The physical mechanisms underpinning the morphological evolution are examined from the viewpoint of energy. Surface curvature is found to play a regulatory role in the pattern evolution. This study may not only help understand the morphogenesis of soft biological tissues, but also inspire novel routes for creating desired surface patterns of soft materials.

Computer-aided diagnosis of focal liver lesions by use of physicians' subjective classification of echogenic patterns in baseline and contrast-enhanced ultrasonography.

PubMed

Sugimoto, Katsutoshi; Shiraishi, Junji; Moriyasu, Fuminori; Doi, Kunio

2009-04-01

To develop a computer-aided diagnostic (CAD) scheme for classifying focal liver lesions (FLLs) by use of physicians' subjective classification of echogenic patterns of FLLs on baseline and contrast-enhanced ultrasonography (US). A total of 137 hepatic lesions in 137 patients were evaluated with B-mode and NC100100 (Sonazoid)-enhanced pulse-inversion US; lesions included 74 hepatocellular carcinomas (HCCs) (23: well-differentiated, 36: moderately differentiated, 15: poorly differentiated HCCs), 33 liver metastases, and 30 liver hemangiomas. Three physicians evaluated single images at B-mode and arterial phases with a cine mode. Physicians were asked to classify each lesion into one of eight B-mode and one of eight enhancement patterns, but did not make a diagnosis. To classify five types of FLLs, we employed a decision tree model with four decision nodes and four artificial neural networks (ANNs). The results of the physicians' pattern classifications were used successively for four different ANNs in making decisions at each of the decision nodes in the decision tree model. The classification accuracies for the 137 FLLs were 84.8% for metastasis, 93.3% for hemangioma, and 98.6% for all HCCs. In addition, the classification accuracies for histological differentiation types of HCCs were 65.2% for well-differentiated HCC, 41.7% for moderately differentiated HCC, and 80.0% for poorly differentiated HCC. This CAD scheme has the potential to improve the diagnostic accuracy of liver lesions. However, the accuracy in the histologic differential diagnosis of HCC based on baseline and contrast-enhanced US is still limited.

Isolation-by-distance in landscapes: considerations for landscape genetics

PubMed Central

van Strien, M J; Holderegger, R; Van Heck, H J

2015-01-01

In landscape genetics, isolation-by-distance (IBD) is regarded as a baseline pattern that is obtained without additional effects of landscape elements on gene flow. However, the configuration of suitable habitat patches determines deme topology, which in turn should affect rates of gene flow. IBD patterns can be characterized either by monotonically increasing pairwise genetic differentiation (for example, FST) with increasing interdeme geographic distance (case-I pattern) or by monotonically increasing pairwise genetic differentiation up to a certain geographical distance beyond which no correlation is detectable anymore (case-IV pattern). We investigated if landscape configuration influenced the rate at which a case-IV pattern changed to a case-I pattern. We also determined at what interdeme distance the highest correlation was measured between genetic differentiation and geographic distance and whether this distance corresponded to the maximum migration distance. We set up a population genetic simulation study and assessed the development of IBD patterns for several habitat configurations and maximum migration distances. We show that the rate and likelihood of the transition of case-IV to case-I FST–distance relationships was strongly influenced by habitat configuration and maximum migration distance. We also found that the maximum correlation between genetic differentiation and geographic distance was not related to the maximum migration distance and was measured across all deme pairs in a case-I pattern and, for a case-IV pattern, at the distance where the FST–distance curve flattens out. We argue that in landscape genetics, separate analyses should be performed to either assess IBD or the landscape effects on gene flow. PMID:25052412

Microenvironments engineered by inkjet bioprinting spatially direct adult stem cells toward muscle- and bone-like subpopulations.

PubMed

Phillippi, Julie A; Miller, Eric; Weiss, Lee; Huard, Johnny; Waggoner, Alan; Campbell, Phil

2008-01-01

In vivo, growth factors exist both as soluble and as solid-phase molecules, immobilized to cell surfaces and within the extracellular matrix. We used this rationale to develop more biologically relevant approaches to study stem cell behaviors. We engineered stem cell microenvironments using inkjet bioprinting technology to create spatially defined patterns of immobilized growth factors. Using this approach, we engineered cell fate toward the osteogenic lineage in register to printed patterns of bone morphogenetic protein (BMP) 2 contained within a population of primary muscle-derived stem cells (MDSCs) isolated from adult mice. This patterning approach was conducive to patterning the MDSCs into subpopulations of osteogenic or myogenic cells simultaneously on the same chip. When cells were cultured under myogenic conditions on BMP-2 patterns, cells on pattern differentiated toward the osteogenic lineage, whereas cells off pattern differentiated toward the myogenic lineage. Time-lapse microscopy was used to visualize the formation of multinucleated myotubes, and immunocytochemistry was used to demonstrate expression of myosin heavy chain (fast) in cells off BMP-2 pattern. This work provides proof-of-concept for engineering spatially controlled multilineage differentiation of stem cells using patterns of immobilized growth factors. This approach may be useful for understanding cell behaviors to immobilized biological patterns and could have potential applications for regenerative medicine.

A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration.

PubMed

Kuttippurathu, Lakshmi; Patra, Biswanath; Hoek, Jan B; Vadigepalli, Rajanikanth

2016-03-01

Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze the genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to the regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1 h post PHx. This set was associated with the regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1 h binding targets showed ethanol-specific differential expression through 6 h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx.

Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation

PubMed Central

Kinjyo, Ichiko; Qin, Jim; Tan, Sioh-Yang; Wellard, Cameron J.; Mrass, Paulus; Ritchie, William; Doi, Atsushi; Cavanagh, Lois L.; Tomura, Michio; Sakaue-Sawano, Asako; Kanagawa, Osami; Miyawaki, Atsushi; Hodgkin, Philip D.; Weninger, Wolfgang

2015-01-01

The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8+ T cells. During influenza virus infection in vivo, naive T cells enter a CD62Lintermediate state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62Lhi central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62Lhi memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways. PMID:25709008

Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation.

PubMed

Kinjyo, Ichiko; Qin, Jim; Tan, Sioh-Yang; Wellard, Cameron J; Mrass, Paulus; Ritchie, William; Doi, Atsushi; Cavanagh, Lois L; Tomura, Michio; Sakaue-Sawano, Asako; Kanagawa, Osami; Miyawaki, Atsushi; Hodgkin, Philip D; Weninger, Wolfgang

2015-02-24

The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8(+) T cells. During influenza virus infection in vivo, naive T cells enter a CD62L(intermediate) state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62L(hi) central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62L(hi) memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways.

ITRAQ-based quantitative proteomic analysis of Cynops orientalis limb regeneration.

PubMed

Tang, Jie; Yu, Yuan; Zheng, Hanxue; Yin, Lu; Sun, Mei; Wang, Wenjun; Cui, Jihong; Liu, Wenguang; Xie, Xin; Chen, Fulin

2017-09-22

Salamanders regenerate their limbs after amputation. However, the molecular mechanism of this unique regeneration remains unclear. In this study, isobaric tags for relative and absolute quantification (iTRAQ) coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS) was employed to quantitatively identify differentially expressed proteins in regenerating limbs 3, 7, 14, 30 and 42 days post amputation (dpa). Of 2636 proteins detected in total, 253 proteins were differentially expressed during different regeneration stages. Among these proteins, Asporin, Cadherin-13, Keratin, Collagen alpha-1(XI) and Titin were down-regulated. CAPG, Coronin-1A, AnnexinA1, Cathepsin B were up-regulated compared with the control. The identified proteins were further analyzed to obtain information about their expression patterns and functions in limb regeneration. Functional analysis indicated that the differentially expressed proteins were associated with wound healing, immune response, cellular process, metabolism and binding. This work indicated that significant proteome alternations occurred during salamander limb regeneration. The results may provide fundamental knowledge to understand the mechanism of limb regeneration.

Geometric morphometrics reveals sex-differential shape allometry in a spider.

PubMed

Fernández-Montraveta, Carmen; Marugán-Lobón, Jesús

2017-01-01

Common scientific wisdom assumes that spider sexual dimorphism (SD) mostly results from sexual selection operating on males. However, testing predictions from this hypothesis, particularly male size hyperallometry, has been restricted by methodological constraints. Here, using geometric morphometrics (GMM) we studied for the first time sex-differential shape allometry in a spider ( Donacosa merlini , Araneae: Lycosidae) known to exhibit the reverse pattern (i.e., male-biased) of spider sexual size dimorphism. GMM reveals previously undetected sex-differential shape allometry and sex-related shape differences that are size independent (i.e., associated to the y-intercept, and not to size scaling). Sexual shape dimorphism affects both the relative carapace-to-opisthosoma size and the carapace geometry, arguably resulting from sex differences in both reproductive roles (female egg load and male competition) and life styles (wandering males and burrowing females). Our results demonstrate that body portions may vary modularly in response to different selection pressures, giving rise to sex differences in shape, which reconciles previously considered mutually exclusive interpretations about the origins of spider SD.

Real-Time Maps of Fluid Flow Fields in Porous Biomaterials

PubMed Central

Mack, Julia J.; Youssef, Khalid; Noel, Onika D.V.; Lake, Michael P.; Wu, Ashley; Iruela-Arispe, M. Luisa; Bouchard, Louis-S.

2013-01-01

Mechanical forces such as fluid shear have been shown to enhance cell growth and differentiation, but knowledge of their mechanistic effect on cells is limited because the local flow patterns and associated metrics are not precisely known. Here we present real-time, noninvasive measures of local hydrodynamics in 3D biomaterials based on nuclear magnetic resonance. Microflow maps were further used to derive pressure, shear and fluid permeability fields. Finally, remodeling of collagen gels in response to precise fluid flow parameters was correlated with structural changes. It is anticipated that accurate flow maps within 3D matrices will be a critical step towards understanding cell behavior in response to controlled flow dynamics. PMID:23245922

A meta-analysis of cambium phenology and growth: linear and non-linear patterns in conifers of the northern hemisphere.

PubMed

Rossi, Sergio; Anfodillo, Tommaso; Cufar, Katarina; Cuny, Henri E; Deslauriers, Annie; Fonti, Patrick; Frank, David; Gricar, Jozica; Gruber, Andreas; King, Gregory M; Krause, Cornelia; Morin, Hubert; Oberhuber, Walter; Prislan, Peter; Rathgeber, Cyrille B K

2013-12-01

Ongoing global warming has been implicated in shifting phenological patterns such as the timing and duration of the growing season across a wide variety of ecosystems. Linear models are routinely used to extrapolate these observed shifts in phenology into the future and to estimate changes in associated ecosystem properties such as net primary productivity. Yet, in nature, linear relationships may be special cases. Biological processes frequently follow more complex, non-linear patterns according to limiting factors that generate shifts and discontinuities, or contain thresholds beyond which responses change abruptly. This study investigates to what extent cambium phenology is associated with xylem growth and differentiation across conifer species of the northern hemisphere. Xylem cell production is compared with the periods of cambial activity and cell differentiation assessed on a weekly time scale on histological sections of cambium and wood tissue collected from the stems of nine species in Canada and Europe over 1-9 years per site from 1998 to 2011. The dynamics of xylogenesis were surprisingly homogeneous among conifer species, although dispersions from the average were obviously observed. Within the range analysed, the relationships between the phenological timings were linear, with several slopes showing values close to or not statistically different from 1. The relationships between the phenological timings and cell production were distinctly non-linear, and involved an exponential pattern. The trees adjust their phenological timings according to linear patterns. Thus, shifts of one phenological phase are associated with synchronous and comparable shifts of the successive phases. However, small increases in the duration of xylogenesis could correspond to a substantial increase in cell production. The findings suggest that the length of the growing season and the resulting amount of growth could respond differently to changes in environmental conditions.

Suppressive subtractive hybridization approach revealed differential expression of hypersensitive response and reactive oxygen species production genes in tea (Camellia sinensis (L.) O. Kuntze) leaves during Pestalotiopsis thea infection.

PubMed

Senthilkumar, Palanisamy; Thirugnanasambantham, Krishnaraj; Mandal, Abul Kalam Azad

2012-12-01

Tea (Camellia sinensis (L.) O. Kuntze) is an economically important plant cultivated for its leaves. Infection of Pestalotiopsis theae in leaves causes gray blight disease and enormous loss to the tea industry. We used suppressive subtractive hybridization (SSH) technique to unravel the differential gene expression pattern during gray blight disease development in tea. Complementary DNA from P. theae-infected and uninfected leaves of disease tolerant cultivar UPASI-10 was used as tester and driver populations respectively. Subtraction efficiency was confirmed by comparing abundance of β-actin gene. A total of 377 and 720 clones with insert size >250 bp from forward and reverse library respectively were sequenced and analyzed. Basic Local Alignment Search Tool analysis revealed 17 sequences in forward SSH library have high degree of similarity with disease and hypersensitive response related genes and 20 sequences with hypothetical proteins while in reverse SSH library, 23 sequences have high degree of similarity with disease and stress response-related genes and 15 sequences with hypothetical proteins. Functional analysis indicated unknown (61 and 59 %) or hypothetical functions (23 and 18 %) for most of the differentially regulated genes in forward and reverse SSH library, respectively, while others have important role in different cellular activities. Majority of the upregulated genes are related to hypersensitive response and reactive oxygen species production. Based on these expressed sequence tag data, putative role of differentially expressed genes were discussed in relation to disease. We also demonstrated the efficiency of SSH as a tool in enriching gray blight disease related up- and downregulated genes in tea. The present study revealed that many genes related to disease resistance were suppressed during P. theae infection and enhancing these genes by the application of inducers may impart better disease tolerance to the plants.

Odour discrimination learning in the Indian greater short-nosed fruit bat (Cynopterus sphinx): differential expression of Egr-1, C-fos and PP-1 in the olfactory bulb, amygdala and hippocampus.

PubMed

Mukilan, Murugan; Bogdanowicz, Wieslaw; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel

2018-06-15

Activity-dependent expression of immediate-early genes (IEGs) is induced by exposure to odour. The present study was designed to investigate whether there is differential expression of IEGs ( Egr-1 , C-fos ) in the brain region mediating olfactory memory in the Indian greater short-nosed fruit bat, Cynopterus sphinx We assumed that differential expression of IEGs in different brain regions may orchestrate a preference odour (PO) and aversive odour (AO) memory in C. sphinx We used preferred (0.8% w/w cinnamon powder) and aversive (0.4% w/v citral) odour substances, with freshly prepared chopped apple, to assess the behavioural response and induction of IEGs in the olfactory bulb, hippocampus and amygdala. After experiencing PO and AO, the bats initially responded to both, later only engaging in feeding bouts in response to the PO food. The expression pattern of EGR-1 and c-Fos in the olfactory bulb, hippocampus and amygdala was similar at different time points (15, 30 and 60 min) following the response to PO, but was different for AO. The response to AO elevated the level of c-Fos expression within 30 min and reduced it at 60 min in both the olfactory bulb and the hippocampus, as opposed to the continuous increase noted in the amygdala. In addition, we tested whether an epigenetic mechanism involving protein phosphatase-1 (PP-1) acts on IEG expression. The observed PP-1 expression and the level of unmethylated/methylated promoter revealed that C-fos expression is possibly controlled by odour-mediated regulation of PP-1. These results in turn imply that the differential expression of C-fos in the hippocampus and amygdala may contribute to olfactory learning and memory in C. sphinx . © 2018. Published by The Company of Biologists Ltd.

Response of microRNAs to cold treatment in the young spikes of common wheat.

PubMed

Song, Guoqi; Zhang, Rongzhi; Zhang, Shujuan; Li, Yulian; Gao, Jie; Han, Xiaodong; Chen, Mingli; Wang, Jiao; Li, Wei; Li, Genying

2017-02-28

MicroRNAs (miRNAs) are a class of small non-coding RNAs that play important roles in biotic and abiotic stresses by regulating their target genes. For common wheat, spring frost damage frequently occurs, especially when low temperature coincides with plants at early floral organ differentiation, which may result in significant yield loss. Up to date, the role of miRNAs in wheat response to frost stress is not well understood. We report here the sequencing of small RNA transcriptomes from the young spikes that were treated with cold stress and the comparative analysis with those of the control. A total of 192 conserved miRNAs from 105 families and nine novel miRNAs were identified. Among them, 34 conserved and five novel miRNAs were differentially expressed between the cold-stressed samples and the controls. The expression patterns of 18 miRNAs were further validated by quantitative real time polymerase chain reaction (qRT-PCR). Moreover, nearly half of the miRNAs were cross inducible by biotic and abiotic stresses when compared with previously published work. Target genes were predicted and validated by degradome sequencing. Gene Ontology (GO) enrichment analysis showed that the target genes of differentially expressed miRNAs were enriched for response to the stimulus, regulation of transcription, and ion transport functions. Since many targets of differentially expressed miRNAs were transcription factors that are associated with floral development such as ARF, SPB (Squamosa Promoter Binding like protein), MADS-box (MCM1, AG, DEFA and SRF), MYB, SPX (SYG1, Pho81 and XPR1), TCP (TEOSINTE BRANCHED, Cycloidea and PCF), and PPR (PentatricoPeptide Repeat) genes, cold-altered miRNA expression may cause abnormal reproductive organ development. Analysis of small RNA transcriptomes and their target genes provide new insight into miRNA regulation in developing wheat inflorescences under cold stress. MiRNAs provide another layer of gene regulation in cold stress response that can be genetically manipulated to reduce yield loss in wheat.

Functionality and Evolutionary History of the Chaperonins in Thermophilic Archaea. A Bioinformatical Perspective

NASA Technical Reports Server (NTRS)

Karlin, Samuel

2004-01-01

We used bioinformatics methods to study phylogenetic relations and differentiation patterns of the archaeal chaperonin 60 kDa heat-shock protein (HSP60) genes in support of the study of differential expression patterns of the three chaperonin genes encoded in Sulfolobus shibatae.

Micro-Topographies Promote Late Chondrogenic Differentiation Markers in the ATDC5 Cell Line.

PubMed

Le, Bach Q; Vasilevich, Aliaksei; Vermeulen, Steven; Hulshof, Frits; Stamatialis, Dimitrios F; van Blitterswijk, Clemens A; de Boer, Jan

2017-05-01

Chemical and mechanical cues are well-established influencers of in vitro chondrogenic differentiation of ATDC5 cells. Here, we investigate the role of topographical cues in this differentiation process, a study not been explored before. Previously, using a library of surface micro-topographies we found some distinct patterns that induced alkaline phosphatase (ALP) production in human mesenchymal stromal cells. ALP is also a marker for hypertrophy, the end stage of chondrogenic differentiation preceding bone formation. Thus, we hypothesized that these patterns could influence end-stage chondrogenic differentiation of ATDC5 cells. In this study, we randomly selected seven topographies among the ALP influencing hits. Cells grown on these surfaces displayed varying nuclear shape and actin filament structure. When stimulated with insulin-transferrin-selenium (ITS) medium, nodule formation occurred and in some cases showed alignment to the topographical patterns. Gene expression analysis of cells growing on topographical surfaces in the presence of ITS medium revealed a downregulation of early markers and upregulation of late markers of chondrogenic differentiation compared to cells grown on a flat surface. In conclusion, we demonstrated that surface topography in addition to other cues can promote hypertrophic differentiation suitable for bone tissue engineering.

Profiling and Quantifying Differential Gene Transcription Provide Insights into Ganoderic Acid Biosynthesis in Ganoderma lucidum in Response to Methyl Jasmonate

PubMed Central

Shi, Liang; Mu, Da-Shuai; Jiang, Ai-Liang; Han, Qin; Zhao, Ming-Wen

2013-01-01

Ganoderma lucidum is a mushroom with traditional medicinal properties that has been widely used in China and other countries in Eastern Asia. Ganoderic acids (GA) produced by G. lucidum exhibit important pharmacological activities. Previous studies have demonstrated that methyl jasmonate (MeJA) is a potent inducer of GA biosynthesis and the expression of genes involved in the GA biosynthesis pathway in G. lucidum. To further explore the mechanism of GA biosynthesis, cDNA-Amplified Fragment Length Polymorphism (cDNA-AFLP) was used to identify genes that are differentially expressed in response to MeJA. Using 64 primer combinations, over 3910 transcriptionally derived fragments (TDFs) were obtained. Reliable sequence data were obtained for 390 of 458 selected TDFs. Ninety of these TDFs were annotated with known functions through BLASTX searching the GenBank database, and 12 annotated TDFs were assigned into secondary metabolic pathways by searching the KEGGPATHWAY database. Twenty-five TDFs were selected for qRT-PCR analysis to confirm the expression patterns observed with cDNA-AFLP. The qRT-PCR results were consistent with the altered patterns of gene expression revealed by the cDNA-AFLP technique. Additionally, the transcript levels of 10 genes were measured at the mycelium, primordia, and fruiting body developmental stages of G. lucidum. The greatest expression levels were reached during primordia for all of the genes except cytochrome b2 reached its highest expression level in the mycelium stage. This study not only identifies new candidate genes involved in the regulation of GA biosynthesis but also provides further insight into MeJA-induced gene expression and secondary metabolic response in G. lucidum. PMID:23762280

Patient-Specific Computational Modeling of Keratoconus Progression and Differential Responses to Collagen Cross-linking

PubMed Central

Sinha Roy, Abhijit

2011-01-01

Purpose. To model keratoconus (KC) progression and investigate the differential responses of central and eccentric cones to standard and alternative collagen cross-linking (CXL) patterns. Methods. Three-dimensional finite element models (FEMs) were generated with clinical tomography and IOP measurements. Graded reductions in regional corneal hyperelastic properties and thickness were imposed separately in the less affected eye of a KC patient. Topographic results, including maximum curvature and first-surface, higher-order aberrations (HOAs), were compared to those of the more affected contralateral eye. In two eyes with central and eccentric cones, a standard broad-beam CXL protocol was simulated with 200- and 300-μm treatment depths and compared to spatially graded broad-beam and cone-centered CXL simulations. Results. In a model of KC progression, maximum curvature and HOA increased as regional corneal hyperelastic properties were decreased. A topographic cone could be generated without a reduction in corneal thickness. Simulation of standard 9-mm-diameter CXL produced decreases in corneal curvature comparable to clinical reports and affected cone location. A 100-μm increase in CXL depth enhanced flattening by 24% to 34% and decreased HOA by 22% to 31%. Topographic effects were greatest with cone-centered CXL simulations. Conclusions. Progressive hyperelastic weakening of a cornea with subclinical KC produced topographic features of manifest KC. The clinical phenomenon of topographic flattening after CXL was replicated. The magnitude and higher-order optics of this response depended on IOP and the spatial distribution of stiffening relative to the cone location. Smaller diameter simulated treatments centered on the cone provided greater reductions in curvature and HOA than a standard broad-beam CXL pattern. PMID:22039252

Combining Population Structure with Historic Abitoic Processes to Better Understand Species and Community Range Shifts in Response to Climate Change

NASA Astrophysics Data System (ADS)

Graham, N. M.

2015-12-01

The evolution and speciation of plants is directly tied to the environment as the constrained stages of dispersal creates strong genetic differentiation among populations. This can result in differing genetic patterns between nuclear and chloroplast loci, where genes are inherited differently and dispersed via separate vectors. By developing distribution models based on genetic patterns found within a species, it is possible to begin understanding the influence of historic geomorphic and/or climatic processes on population evolution. If genetic patterns of the current range correlate with specific patterns of climate variability within the Pleistocene, it is possible that future shifts in species distribution in response to climate change can be more accurately modelled due to the historic signature that is found within inherited genes. Preliminary genetic analyses of Linanthus dichotomus, an annual herb distributed across California, suggests that the current taxonomic treatment does not accurately depict how this species is evolving. Genetic patterns of chloroplast genes suggest that populations are more correlated with biogeography than what the current nomenclature states. Additionally, chloroplast and nuclear genes show discrepancies in the dispersal across the landscape, suggesting pollinator driven gene flow overcoming seed dispersal boundaries. By comparing discrepancies between pollinator and seed induced gene flow we may be able to gain insight into historical pollinator communities within the Pleistocene. This information can then be applied to projected climate models to more accurately understand how species and/or communities will respond to a changing environment.

Combination of oriented partial differential equation and shearlet transform for denoising in electronic speckle pattern interferometry fringe patterns.

PubMed

Xu, Wenjun; Tang, Chen; Gu, Fan; Cheng, Jiajia

2017-04-01

It is a key step to remove the massive speckle noise in electronic speckle pattern interferometry (ESPI) fringe patterns. In the spatial-domain filtering methods, oriented partial differential equations have been demonstrated to be a powerful tool. In the transform-domain filtering methods, the shearlet transform is a state-of-the-art method. In this paper, we propose a filtering method for ESPI fringe patterns denoising, which is a combination of second-order oriented partial differential equation (SOOPDE) and the shearlet transform, named SOOPDE-Shearlet. Here, the shearlet transform is introduced into the ESPI fringe patterns denoising for the first time. This combination takes advantage of the fact that the spatial-domain filtering method SOOPDE and the transform-domain filtering method shearlet transform benefit from each other. We test the proposed SOOPDE-Shearlet on five experimentally obtained ESPI fringe patterns with poor quality and compare our method with SOOPDE, shearlet transform, windowed Fourier filtering (WFF), and coherence-enhancing diffusion (CEDPDE). Among them, WFF and CEDPDE are the state-of-the-art methods for ESPI fringe patterns denoising in transform domain and spatial domain, respectively. The experimental results have demonstrated the good performance of the proposed SOOPDE-Shearlet.

Combination of elastography and tissue quantification using the acoustic radiation force impulse (ARFI) technology for differential diagnosis of breast masses.

PubMed

Tozaki, Mitsuhiro; Isobe, Sachiko; Sakamoto, Masaaki

2012-10-01

We evaluated the diagnostic performance of elastography and tissue quantification using acoustic radiation force impulse (ARFI) technology for differential diagnosis of breast masses. There were 161 mass lesions. First, lesion correspondence on ARFI elastographic images to those on the B-mode images was evaluated: no findings on ARFI images (pattern 1), lesions that were bright inside (pattern 2), lesions that were dark inside (pattern 4), lesions that contained both bright and dark areas (pattern 3). In addition, pattern 4 was subdivided into 4a (dark area same as B-mode lesion) and 4b (dark area larger than lesion). Next, shear wave velocity (SWV) was measured using virtual touch tissue quantification. There were 13 pattern 1 lesions and five pattern 2 lesions; all of these lesions were benign, whereas all pattern 4b lesions (n = 43) were malignant. When the value of 3.59 m/s was chosen as the cutoff value, the combination of elastography and tissue quantification showed 91 % (83-91) sensitivity, 93 % (65-70) specificity, and 92 % (148-161) accuracy. The combination of elastography and tissue quantification is thought to be a promising ultrasound technique for differential diagnosis of breast-mass lesions.

Chronic Malaria Revealed by a New Fluorescence Pattern on the Antinuclear Autoantibodies Test

PubMed Central

Hommel, Benjamin; Charuel, Jean-Luc; Jaureguiberry, Stéphane; Arnaud, Laurent; Courtin, Regis; Kassab, Petra; Prendki, Virginie; Paris, Luc; Ghillani-Dalbin, Pascale; Thellier, Marc; Caumes, Eric; Amoura, Zahir; Mazier, Dominique; Musset, Lucile; Buffet, Pierre; Miyara, Makoto

2014-01-01

Background Several clinical forms of malaria such as chronic carriage, gestational malaria or hyper-reactive malarial splenomegaly may follow a cryptic evolution with afebrile chronic fatigue sometimes accompanied by anemia and/or splenomegaly. Conventional parasitological tests are often negative or not performed, and severe complications may occur. Extensive explorations of these conditions often include the search for antinuclear autoantibodies (ANA). Methods We analysed fluorescence patterns in the ANA test in patients with either chronic cryptic or acute symptomatic malaria, then conducted a one-year prospective study at a single hospital on all available sera drawn for ANA detections. We then identified autoantibodies differentially expressed in malaria patients and in controls using human protein microarray. Results We uncovered and defined a new, malaria-related, nucleo-cytoplasmic ANA pattern displaying the specific association of a nuclear speckled pattern with diffuse cytoplasmic perinuclearly-enhanced fluorescence. In the one-year prospective analysis, 79% of sera displaying this new nucleo-cytoplasmic fluorescence were from patients with malaria. This specific pattern, not seen in other parasitic diseases, allowed a timely reorientation of the diagnosis toward malaria. To assess if the autoantibody immune response was due to autoreactivity or molecular mimicry we isolated 42 autoantigens, targets of malarial autoantibodies. BLAST analysis indicated that 23 of recognized autoantigens were homologous to plasmodial proteins suggesting autoimmune responses directly driven by the plasmodial infection. Conclusion In patients with malaria in whom parasitological tests have not been performed recognition of this new, malaria-related fluorescence pattern on the ANA test is highly suggestive of the diagnosis and triggers immediate, easy confirmation and adapted therapy. PMID:24551116

Physiological and Biochemical Changes Reveal Differential Patterns of Docosahexaenoic Acid Partitioning in Two Marine Algal Strains of Isochrysis

PubMed Central

Chen, Yong; Mao, Xuemei; Liu, Jin

2017-01-01

The marine microalgae Isochrysis are a good producer of natural docosahexaenoic acid (DHA). To better understand the patterns of DHA accumulation and distribution, two Isochrysis strains, CL153180 and CCMP462, were evaluated in this study. In a batch culture, CL153180 showed a decline in DHA content while CCMP462 exhibited a progressive increase during the late growth period when nitrogen was almost exhausted. In response to nitrogen deficiency (ND), both strains showed a considerable increase in neutral lipids (NL) at the expense of glycolipids (GL) but had little variation in phospholipids (PL). In CL153180, the DHA percentage of NL decreased gradually upon ND, while that in CCMP462 increased progressively to 21.4% after 4 days of ND, which is around 5-fold higher than CL153180. Accordingly, in contrast to CL153180 that stored DHA predominantly in GL, CCMP462 accumulated DHA mainly in NL in late days of ND. Taken together, we proposed a working model for the differential DHA partitioning patterns between two Isochrysis strains: for CCMP462, the degradation of GL released free fatty acids including DHA, which was incorporated into NL upon ND; whereas for CL153180, the released DHA from GL might not be incorporated into NL, and, consequently, might be subject to β-oxidation for degradation. PMID:29137149

DNA topoisomerase IIβ stimulates neurite outgrowth in neural differentiated human mesenchymal stem cells through regulation of Rho-GTPases (RhoA/Rock2 pathway) and Nurr1 expression.

PubMed

Zaim, Merve; Isik, Sevim

2018-04-25

DNA topoisomerase IIβ (topo IIβ) is known to regulate neural differentiation by inducing the neuronal genes responsible for critical neural differentiation events such as neurite outgrowth and axon guidance. However, the pathways of axon growth controlled by topo IIβ have not been clarified yet. Microarray results of our previous study have shown that topo IIβ silencing in neural differentiated primary human mesenchymal stem cells (hMSCs) significantly alters the expression pattern of genes involved in neural polarity, axonal growth, and guidance, including Rho-GTPases. This study aims to further analyze the regulatory role of topo IIβ on the process of axon growth via regulation of Rho-GTPases. For this purpose, topo IIβ was silenced in neurally differentiated hMSCs. Cells lost their morphology because of topo IIβ deficiency, becoming enlarged and flattened. Additionally, a reduction in both neural differentiation efficiency and neurite length, upregulation in RhoA and Rock2, downregulation in Cdc42 gene expression were detected. On the other hand, cells were transfected with topo IIβ gene to elucidate the possible neuroprotective effect of topo IIβ overexpression on neural-induced hMSCs. Topo IIβ overexpression prompted all the cells to exhibit neural cell morphology as characterized by longer neurites. RhoA and Rock2 expressions were downregulated, whereas Cdc42 expression was upregulated. Nurr1 expression level correlated with topo IIβ in both topo IIβ-overexpressed and -silenced cells. Furthermore, differential translocation of Rho-GTPases was detected by immunostaining in response to topo IIβ. Our results suggest that topo IIβ deficiency could give rise to neurodegeneration through dysregulation of Rho-GTPases. However, further in-vivo research is needed to demonstrate if re-regulation of Rho GTPases by topo IIβ overexpression could be a neuroprotective treatment in the case of neurodegenerative diseases.

The comparative phylogeography of east coast estuarine fishes in formerly glaciated sites: Persistence versus recolonization in Cyprinodon variegatus ovinus and Fundulus heteroclitus macrolepidotus.

PubMed

Haney, Robert A; Dionne, Michelle; Puritz, Jon; Rand, David M

2009-01-01

Species distributions may be dramatically affected by climatic variability, such as occurred during Pleistocene glaciation. Populations of coastal organisms could have been affected directly by ice movement or through sea level change. Response could involve shifts in distribution southwards or persistence through the full range or in limited high-latitude refugia. Comparative studies of the response of ecologically similar species can provide a useful complement to those examining response across disparate species in defining what parameters influence persistence. Patterns of mitochondrial genetic variation in 2 estuarine fish subspecies from the Northwest Atlantic, Fundulus heteroclitus macrolepidotus and Cyprinodon variegatus ovinus, indicate that ecological similarity does not necessarily predict propensity for glacial persistence. Fundulus heteroclitus macrolepidotus is highly diverse in glaciated regions, with isolated populations whose origins predate the last glacial maximum and may have recently expanded it's range to the south from New England. However, within glaciated regions, signals of population growth and distributional shifts indicate a dynamic Pleistocene history for F. h. macrolepidotus, in contrast with recent studies involving microsatellites. A different pattern is found in C. v. ovinus, which is depauperate in formerly glaciated sites, with a clear signal of recent recolonization of glaciated regions from the south. Genetic differentiation in glaciated areas is consistent with isolation after glacial withdrawal. In C. v. ovinus, rapidly evolving microsatellite loci show a similar pattern to mitochondrial DNA but may be reaching equilibrium on small spatial scales. These contrasting patterns of variation illustrate how ecologically similar species can respond to large-scale environmental change in distinct ways.

Network patterns in exponentially growing two-dimensional biofilms

NASA Astrophysics Data System (ADS)

Zachreson, Cameron; Yap, Xinhui; Gloag, Erin S.; Shimoni, Raz; Whitchurch, Cynthia B.; Toth, Milos

2017-10-01

Anisotropic collective patterns occur frequently in the morphogenesis of two-dimensional biofilms. These patterns are often attributed to growth regulation mechanisms and differentiation based on gradients of diffusing nutrients and signaling molecules. Here, we employ a model of bacterial growth dynamics to show that even in the absence of growth regulation or differentiation, confinement by an enclosing medium such as agar can itself lead to stable pattern formation over time scales that are employed in experiments. The underlying mechanism relies on path formation through physical deformation of the enclosing environment.

Genome-wide characterization of differentially expressed genes provides insights into regulatory network of heat stress response in radish (Raphanus sativus L.).

PubMed

Wang, Ronghua; Mei, Yi; Xu, Liang; Zhu, Xianwen; Wang, Yan; Guo, Jun; Liu, Liwang

2018-03-01

Heat stress (HS) causes detrimental effects on plant morphology, physiology, and biochemistry that lead to drastic reduction in plant biomass production and economic yield worldwide. To date, little is known about HS-responsive genes involved in thermotolerance mechanism in radish. In this study, a total of 6600 differentially expressed genes (DEGs) from the control and Heat24 cDNA libraries of radish were isolated by high-throughput sequencing. With Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, some genes including MAPK, DREB, ERF, AP2, GST, Hsf, and Hsp were predominantly assigned in signal transductions, metabolic pathways, and biosynthesis and abiotic stress-responsive pathways. These pathways played significant roles in reducing stress-induced damages and enhancing heat tolerance in radish. Expression patterns of 24 candidate genes were validated by reverse-transcription quantitative PCR (RT-qPCR). Based mainly on the analysis of DEGs combining with the previous miRNAs analysis, the schematic model of HS-responsive regulatory network was proposed. To counter the effects of HS, a rapid response of the plasma membrane leads to the opening of specific calcium channels and cytoskeletal reorganization, after which HS-responsive genes are activated to repair damaged proteins and ultimately facilitate further enhancement of thermotolerance in radish. These results could provide fundamental insight into the regulatory network underlying heat tolerance in radish and facilitate further genetic manipulation of thermotolerance in root vegetable crops.

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

PubMed

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

2011-11-18

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

Insulin receptor-mediated signaling via phospholipase C-γ regulates growth and differentiation in Drosophila.

PubMed

Murillo-Maldonado, Juan M; Zeineddine, Fouad Bou; Stock, Rachel; Thackeray, Justin; Riesgo-Escovar, Juan R

2011-01-01

Coordination between growth and patterning/differentiation is critical if appropriate final organ structure and size is to be achieved. Understanding how these two processes are regulated is therefore a fundamental and as yet incompletely answered question. Here we show through genetic analysis that the phospholipase C-γ (PLC-γ) encoded by small wing (sl) acts as such a link between growth and patterning/differentiation by modulating some MAPK outputs once activated by the insulin pathway; particularly, sl promotes growth and suppresses ectopic differentiation in the developing eye and wing, allowing cells to attain a normal size and differentiate properly. sl mutants have previously been shown to have a combination of both growth and patterning/differentiation phenotypes: small wings, ectopic wing veins, and extra R7 photoreceptor cells. We show here that PLC-γ activated by the insulin pathway participates broadly and positively during cell growth modulating EGF pathway activity, whereas in cell differentiation PLC-γ activated by the insulin receptor negatively regulates the EGF pathway. These roles require different SH2 domains of PLC-γ, and act via classic PLC-γ signaling and EGF ligand processing. By means of PLC-γ, the insulin receptor therefore modulates differentiation as well as growth. Overall, our results provide evidence that PLC-γ acts during development at a time when growth ends and differentiation begins, and is important for proper coordination of these two processes.

Genetic diversity, structure, and patterns of differentiation in the genus vitis

USDA-ARS?s Scientific Manuscript database

Vitis (Vitaceae) is a taxonomically complicated genus with ca. 60 taxa divided into two subgenera, Vitis and Muscadinia. We used population genetic approaches to gain insights into the genetic diversity, patterns of evolutionary differentiation and to decipher the taxonomic status of some of the con...

Gene expression changes in the retina following subretinal injection of human neural progenitor cells into a rodent model for retinal degeneration.

PubMed

Jones, Melissa K; Lu, Bin; Saghizadeh, Mehrnoosh; Wang, Shaomei

2016-01-01

Retinal degenerative diseases (RDDs) affect millions of people and are the leading cause of vision loss. Although treatment options for RDDs are limited, stem and progenitor cell-based therapies have great potential to halt or slow the progression of vision loss. Our previous studies have shown that a single subretinal injection of human forebrain derived neural progenitor cells (hNPCs) into the Royal College of Surgeons (RCS) retinal degenerate rat offers long-term preservation of photoreceptors and visual function. Furthermore, neural progenitor cells are currently in clinical trials for treating age-related macular degeneration; however, the molecular mechanisms of stem cell-based therapies are largely unknown. This is the first study to analyze gene expression changes in the retina of RCS rats following subretinal injection of hNPCs using high-throughput sequencing. RNA-seq data of retinas from RCS rats injected with hNPCs (RCS(hNPCs)) were compared to sham surgery in RCS (RCS(sham)) and wild-type Long Evans (LE(sham)) rats. Differential gene expression patterns were determined with in silico analysis and confirmed with qRT-PCR. Function, biologic, cellular component, and pathway analyses were performed on differentially expressed genes and investigated with immunofluorescent staining experiments. Analysis of the gene expression data sets identified 1,215 genes that were differentially expressed between RCS(sham) and LE(sham) samples. Additionally, 283 genes were differentially expressed between the RCS(hNPCs) and RCS(sham) samples. Comparison of these two gene sets identified 68 genes with inverse expression (termed rescue genes), including Pdc, Rp1, and Cdc42ep5. Functional, biologic, and cellular component analyses indicate that the immune response is enhanced in RCS(sham). Pathway analysis of the differential expression gene sets identified three affected pathways in RCS(hNPCs), which all play roles in phagocytosis signaling. Immunofluorescent staining detected the increased presence of macrophages and microglia in RCS(sham) retinas, which decreased in RCS(hNPCs) retinas similar to the patterns detected in LE(sham). The results from this study provide evidence of the gene expression changes that occur following treatment with hNPCs in the degenerating retina. This information can be used in future studies to potentially enhance or predict responses to hNPC and other stem cell therapies for retinal degenerative diseases.

Age and prior blood feeding of Anopheles gambiae influences their susceptibility and gene expression patterns to ivermectin-containing blood meals.

PubMed

Seaman, Jonathan A; Alout, Haoues; Meyers, Jacob I; Stenglein, Mark D; Dabiré, Roch K; Lozano-Fuentes, Saul; Burton, Timothy A; Kuklinski, Wojtek S; Black, William C; Foy, Brian D

2015-10-15

Ivermectin has been proposed as a novel malaria transmission control tool based on its insecticidal properties and unique route of acquisition through human blood. To maximize ivermectin's effect and identify potential resistance/tolerance mechanisms, it is important to understand its effect on mosquito physiology and potential to shift mosquito population age-structure. We therefore investigated ivermectin susceptibility and gene expression changes in several age groups of female Anopheles gambiae mosquitoes. The effect of aging on ivermectin susceptibility was analyzed in three age groups (2, 6, and 14-days) of colonized female Anopheles gambiaemosquitoes using standard survivorship assays. Gene expression patterns were then analyzed by transcriptome sequencing on an Illumina HiSeq 2500 platform. RT-qPCR was used to validate transcriptional changes and also to examine expression in a different, colonized strain and in wild mosquitoes, both of which blood fed naturally on an ivermectin-treated person. Mosquitoes of different ages and blood meal history died at different frequencies after ingesting ivermectin. Mortality was lowest in 2-day old mosquitoes exposed on their first blood meal and highest in 6-day old mosquitoes exposed on their second blood meal. Twenty-four hours following ivermectin ingestion, 101 and 187 genes were differentially-expressed relative to control blood-fed, in 2 and 6-day groups, respectively. Transcription patterns of select genes were similar in membrane-fed, colonized, and naturally-fed wild vectors. Transcripts from several unexpected functional classes were highly up-regulated, including Niemann-Pick Type C (NPC) genes, peritrophic matrix-associated genes, and immune-response genes, and these exhibited different transcription patterns between age groups, which may explain the observed susceptibility differences. Niemann-Pick Type 2 genes were the most highly up-regulated transcripts after ivermectin ingestion (up to 160 fold) and comparing phylogeny to transcriptional patterns revealed that NPCs have rapidly evolved and separate members respond to either blood meals or to ivermectin. We present evidence of increased ivermectin susceptibility in older An. gambiae mosquitoes that had previously bloodfed. Differential expression analysis suggests complex midgut interactions resulting from ivermectin ingestion that likely involve blood meal digestion physiological responses, midgut microflora, and innate immune responses. Thus, the transcription of certain gene families is consistently affected by ivermectin ingestion, and may provide important clues to ivermectin's broad effects on malaria vectors. These findings contribute to the growing understanding of ivermectin's potential as a transmission control tool.

Transcriptional analysis of Volvox photoreceptors suggests the existence of different cell-type specific light-signaling pathways.

PubMed

Kianianmomeni, Arash; Hallmann, Armin

2015-02-01

Photosynthetic organisms, e.g., plants including green algae, use a sophisticated light-sensing system, composed of primary photoreceptors and additional downstream signaling components, to monitor changes in the ambient light environment towards adjust their growth and development. Although a variety of cellular processes, e.g., initiation of cleavage division and final cellular differentiation, have been shown to be light-regulated in the green alga Volvox carteri, little is known about the underlying light perception and signaling pathways. This multicellular alga possesses at least 12 photoreceptors, i.e., one phototropin (VcPhot), four cryptochromes (VcCRYa, VcCRYp, VcCRYd1, and VcCRYd2), and seven members of rhodopsin-like photoreceptors (VR1, VChR1, VChR2, VcHKR1, VcHKR2, VcHKR3, and VcHKR4), which display distinct light-dependent chemical processes based on their protein architectures and associated chromophores. Gene expression analyses could show that the transcript levels of some of the photoreceptor genes (e.g., VChR1 and VcHKR1) accumulate during division cleavages, while others (e.g., VcCRYa, VcCRYp, and VcPhot) accumulate during final cellular differentiation. However, the pattern of transcript accumulation changes when the alga switches to the sexual development. Eight photoreceptor genes, e.g., VcPhot, VcCRYp, and VcHKR1, are highly expressed in the somatic cells, while only the animal-type rhodopsin VR1 was found to be highly expressed in the reproductive cells/embryos during both asexual and sexual life cycles. Moreover, accumulation of VChR1 and VcCRYa transcripts is more sensitive to light and changes in response to more than one light quality. Obviously, different regulatory mechanisms underlying gene expression control transcript accumulation of photoreceptors not only during development, but also in a cell-type specific way and in response to various external signals such as light quality. The transcriptional patterns described in this study show that Volvox photoreceptors are mostly expressed in a cell-type specific manner. This gives reason to believe that cell-type specific light-signaling pathways allow differential regulation of cellular and developmental processes in response to the environmental light cues.

Enteric neural crest cells regulate vertebrate stomach patterning and differentiation.

PubMed

Faure, Sandrine; McKey, Jennifer; Sagnol, Sébastien; de Santa Barbara, Pascal

2015-01-15

In vertebrates, the digestive tract develops from a uniform structure where reciprocal epithelial-mesenchymal interactions pattern this complex organ into regions with specific morphologies and functions. Concomitant with these early patterning events, the primitive GI tract is colonized by the vagal enteric neural crest cells (vENCCs), a population of cells that will give rise to the enteric nervous system (ENS), the intrinsic innervation of the GI tract. The influence of vENCCs on early patterning and differentiation of the GI tract has never been evaluated. In this study, we report that a crucial number of vENCCs is required for proper chick stomach development, patterning and differentiation. We show that reducing the number of vENCCs by performing vENCC ablations induces sustained activation of the BMP and Notch pathways in the stomach mesenchyme and impairs smooth muscle development. A reduction in vENCCs also leads to the transdifferentiation of the stomach into a stomach-intestinal mixed phenotype. In addition, sustained Notch signaling activity in the stomach mesenchyme phenocopies the defects observed in vENCC-ablated stomachs, indicating that inhibition of the Notch signaling pathway is essential for stomach patterning and differentiation. Finally, we report that a crucial number of vENCCs is also required for maintenance of stomach identity and differentiation through inhibition of the Notch signaling pathway. Altogether, our data reveal that, through the regulation of mesenchyme identity, vENCCs act as a new mediator in the mesenchymal-epithelial interactions that control stomach development. © 2015. Published by The Company of Biologists Ltd.

Neural Processing of Facial Identity and Emotion in Infants at High-Risk for Autism Spectrum Disorders

PubMed Central

Fox, Sharon E.; Wagner, Jennifer B.; Shrock, Christine L.; Tager-Flusberg, Helen; Nelson, Charles A.

2013-01-01

Deficits in face processing and social impairment are core characteristics of autism spectrum disorder. The present work examined 7-month-old infants at high-risk for developing autism and typically developing controls at low-risk, using a face perception task designed to differentiate between the effects of face identity and facial emotions on neural response using functional Near-Infrared Spectroscopy. In addition, we employed independent component analysis, as well as a novel method of condition-related component selection and classification to identify group differences in hemodynamic waveforms and response distributions associated with face and emotion processing. The results indicate similarities of waveforms, but differences in the magnitude, spatial distribution, and timing of responses between groups. These early differences in local cortical regions and the hemodynamic response may, in turn, contribute to differences in patterns of functional connectivity. PMID:23576966

Identification of NH4+-regulated genes of Herbaspirillum seropedicae by random insertional mutagenesis.

PubMed

Schwab, Stefan; Ramos, Humberto J; Souza, Emanuel M; Pedrosa, Fábio O; Yates, Marshall G; Chubatsu, Leda S; Rigo, Liu U

2007-05-01

Random mutagenesis using transposons with promoterless reporter genes has been widely used to examine differential gene expression patterns in bacteria. Using this approach, we have identified 26 genes of the endophytic nitrogen-fixing bacterium Herbaspirillum seropedicae regulated in response to ammonium content in the growth medium. These include nine genes involved in the transport of nitrogen compounds, such as the high-affinity ammonium transporter AmtB, and uptake systems for alternative nitrogen sources; nine genes coding for proteins responsible for restoring intracellular ammonium levels through enzymatic reactions, such as nitrogenase, amidase, and arginase; and a third group includes metabolic switch genes, coding for sensor kinases or transcription regulation factors, whose role in metabolism was previously unknown. Also, four genes identified were of unknown function. This paper describes their involvement in response to ammonium limitation. The results provide a preliminary profile of the metabolic response of Herbaspirillum seropedicae to ammonium stress.

Immunological modes of pregnancy loss: inflammation, immune effectors, and stress.

PubMed

Kwak-Kim, Joanne; Bao, Shihua; Lee, Sung Ki; Kim, Joon Woo; Gilman-Sachs, Alice

2014-08-01

Inflammatory immune response plays a key role in reproductive failures such as multiple implantation failures (MIF), early pregnancy loss, and recurrent pregnancy losses (RPL). Cellular immune responses particularly mediated by natural killer (NK), and T cells are often dysregulated in these conditions. Excessive or inappropriate recruitment of peripheral blood NK cells to the uterus may lead to cytotoxic environment in utero, in which proliferation and differentiation of trophoblast is hampered. In addition, inadequate angiogenesis by uterine NK cells often leads to abnormal vascular development and blood flow patterns, which, in turn, leads to increased oxidative stress or ischemic changes in the invading trophoblast. T-cell abnormalities with increased Th1 and Th17 immunity, and decreased Th2 and T regulatory immune responses may play important roles in RPL and MIF. A possible role of stress in inflammatory immune response is also reviewed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Measuring Resistance to Change at the Within-Session Level

PubMed Central

Tonneau, François; Ríos, Américo; Cabrera, Felipe

2006-01-01

Resistance to change is often studied by measuring response rate in various components of a multiple schedule. Response rate in each component is normalized (that is, divided by its baseline level) and then log-transformed. Differential resistance to change is demonstrated if the normalized, log-transformed response rate in one component decreases more slowly than in another component. A problem with normalization, however, is that it can produce artifactual results if the relation between baseline level and disruption is not multiplicative. One way to address this issue is to fit specific models of disruption to untransformed response rates and evaluate whether or not a multiplicative model accounts for the data. Here we present such a test of resistance to change, using within-session response patterns in rats as a data base for fitting models of disruption. By analyzing response rate at a within-session level, we were able to confirm a central prediction of the resistance-to-change framework while discarding normalization artifacts as a plausible explanation of our results. PMID:16903495

Measuring resistance to change at the within-session level.

PubMed

Tonneau, François; Ríos, Américo; Cabrera, Felipe

2006-07-01

Resistance to change is often studied by measuring response rate in various components of a multiple schedule. Response rate in each component is normalized (that is, divided by its baseline level) and then log-transformed. Differential resistance to change is demonstrated if the normalized, log-transformed response rate in one component decreases more slowly than in another component. A problem with normalization, however, is that it can produce artifactual results if the relation between baseline level and disruption is not multiplicative. One way to address this issue is to fit specific models of disruption to untransformed response rates and evaluate whether or not a multiplicative model accounts for the data. Here we present such a test of resistance to change, using within-session response patterns in rats as a data base for fitting models of disruption. By analyzing response rate at a within-session level, we were able to confirm a central prediction of the resistance-to-change framework while discarding normalization artifacts as a plausible explanation of our results.

Fasciola gigantica: cercarial shedding pattern from Lymnaea natalensis after long-term exposure to cadmium at different temperatures.

PubMed

Soliman, Maha F M

2009-04-01

Little is known about the response of Fasciola spp., inside its snail host to pollutant toxicity. The effect of long-term exposure of Lymnaea natalensis to 0.1 microg/l, 10 microg/l, or 100 microg/l cadmium (Cd) on the infection rates with F. gigantica, percentage of cercariae-shedding snails and cercariae shedding pattern was investigated. The snails were exposed to Cd for 7 days either pre-infection with single Fasciola miracidium or during the late pre-patent period of the infection. The possible interaction between metal exposure and acclimatization temperature was also studied in three ranges; 16-18 degrees C, 23-25 degrees C and 30-32 degrees C. Results clearly showed that host exposure to 100 microg/l Cd significantly affected the pattern of Fasciola development inside its snail host, and that the acclimatization temperature was a key factor affecting the role played by Cd. Pre-infection exposure to Cd caused a significant reduction in the infection rates where the effect was temperature-dependent. Post-infection exposure to Cd significantly increased the percentage of cercariae-shedding snails; the effect was temperature-independent. Interestingly, post-infection exposure significantly altered the differential cercarial output pattern, while no clear impact on the total was found. The alteration in the differential cercarial output was represented as a significantly higher proportion of floating metacercaria as compared to fixed ones and also higher proportion of dead cercariae which may directly reduce the transmission of Fasciola to the final host. The mechanisms of cadmium impact are briefly discussed.

Time course of gene expression during mouse skeletal muscle hypertrophy

PubMed Central

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

2013-01-01

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

Time course of gene expression during mouse skeletal muscle hypertrophy.

PubMed

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

2013-10-01

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

Insect immunology and hematopoiesis.

PubMed

Hillyer, Julián F

2016-05-01

Insects combat infection by mounting powerful immune responses that are mediated by hemocytes, the fat body, the midgut, the salivary glands and other tissues. Foreign organisms that have entered the body of an insect are recognized by the immune system when pathogen-associated molecular patterns bind host-derived pattern recognition receptors. This, in turn, activates immune signaling pathways that amplify the immune response, induce the production of factors with antimicrobial activity, and activate effector pathways. Among the immune signaling pathways are the Toll, Imd, Jak/Stat, JNK, and insulin pathways. Activation of these and other pathways leads to pathogen killing via phagocytosis, melanization, cellular encapsulation, nodulation, lysis, RNAi-mediated virus destruction, autophagy and apoptosis. This review details these and other aspects of immunity in insects, and discusses how the immune and circulatory systems have co-adapted to combat infection, how hemocyte replication and differentiation takes place (hematopoiesis), how an infection prepares an insect for a subsequent infection (immune priming), how environmental factors such as temperature and the age of the insect impact the immune response, and how social immunity protects entire groups. Finally, this review highlights some underexplored areas in the field of insect immunobiology. Copyright © 2015 Elsevier Ltd. All rights reserved.

It's time to fear! Interval timing in odor fear conditioning in rats

PubMed Central

Shionoya, Kiseko; Hegoburu, Chloé; Brown, Bruce L.; Sullivan, Regina M.; Doyère, Valérie; Mouly, Anne-Marie

2013-01-01

Time perception is crucial to goal attainment in humans and other animals, and interval timing also guides fundamental animal behaviors. Accumulating evidence has made it clear that in associative learning, temporal relations between events are encoded, and a few studies suggest this temporal learning occurs very rapidly. Most of these studies, however, have used methodologies that do not permit investigating the emergence of this temporal learning. In the present study we monitored respiration, ultrasonic vocalization (USV) and freezing behavior in rats in order to perform fine-grain analysis of fear responses during odor fear conditioning. In this paradigm an initially neutral odor (the conditioned stimulus, CS) predicted the arrival of an aversive unconditioned stimulus (US, footshock) at a fixed 20-s time interval. We first investigated the development of a temporal pattern of responding related to CS-US interval duration. The data showed that during acquisition with odor-shock pairings, a temporal response pattern of respiration rate was observed. Changing the CS-US interval duration from 20-s to 30-s resulted in a shift of the temporal response pattern appropriate to the new duration thus demonstrating that the pattern reflected the learning of the CS-US interval. A temporal pattern was also observed during a retention test 24 h later for both respiration and freezing measures, suggesting that the animals had stored the interval duration in long-term memory. We then investigated the role of intra-amygdalar dopaminergic transmission in interval timing. For this purpose, the D1 dopaminergic receptors antagonist SCH23390 was infused in the basolateral amygdala before conditioning. This resulted in an alteration of timing behavior, as reflected in differential temporal patterns between groups observed in a 24 h retention test off drug. The present data suggest that D1 receptor dopaminergic transmission within the amygdala is involved in temporal processing. PMID:24098277

Expression of toll-like receptors 2 and 4 and CD14 during differentiation of HL-60 cells induced by phorbol 12-myristate 13-acetate and 1 alpha, 25-dihydroxy-vitamin D(3).

PubMed

Li, Changlin; Wang, Yibing; Gao, Li; Zhang, Jingsong; Shao, Jie; Wang, Shengnian; Feng, Weiguo; Wang, Xingyu; Li, Minglie; Chang, Zongliang

2002-01-01

Macrophages form a crucial bridge between the innate and adaptive immune response. One of their most important functions is to recognize infectious microorganisms. Toll-like receptors (TLRs) are key elements in pathogen recognition, and among them, TLR2 and TLR4 are most discussed. However, expression patterns of TLRs during myeloid cell differentiation to macrophage are unknown. In this study, we examined differentiation in the model human myeloid cell line, HL-60, treated with phorbol 12-myristate 13-acetate (PMA) or VitD(3). Expression of TLR2, TLR4, and CD14 were measured by reverse transcription-PCR, RNase protection assay, and fluorescence-activated cell sorter assays. After treatment by PMA (1, 10, and 100 nM) for 12, 24, and 48 h, expression of TLR2 and CD14 mRNA was increased in a time- and dose-dependent manner. However, VitD(3) only induced expression of CD14 but not TLR2 in HL-60 cells. TLR4 was expressed constitutively before differentiation and increased slightly after that. Thus, PMA-mediated differentiation of HL-60 cells to macrophages is associated largely with TLR2 expression and, to a much lesser extent, with TLR4. Furthermore, up-regulation of TLR2 and CD14 mRNA expression by PMA was abrogated by a protein kinase C inhibitor, Calphostine C, suggesting the up-regulation of TLR2 and CD14 mRNA is dependent on the activation of protein kinase C. Coexpression of CD14/TLR2 and/or CD14/TLR4 may be essential but not sufficient for the production of tumor necrosis factor-alpha in response to lipopolysaccharide in our system.

Direct Toll-like receptor-mediated stimulation of hematopoietic stem and progenitor cells occurs in vivo and promotes differentiation toward macrophages.

PubMed

Megías, Javier; Yáñez, Alberto; Moriano, Silvia; O'Connor, José-Enrique; Gozalbo, Daniel; Gil, María-Luisa

2012-07-01

As Toll-like receptors (TLRs) are expressed by hematopoietic stem and progenitor cells (HSPCs), they may play a role in hematopoiesis in response to pathogens during infection. We show here that TLR2, TLR4, and TLR9 agonists (tripalmitoyl-S-glyceryl-L-Cys-Ser-(Lys)4 [Pam3CSK4], lipopolysaccharide [LPS], and CpG oligodeoxynucleotide [ODN]) induce the in vitro differentiation of purified murine lineage negative cells (Lin(-) ) as well as HSPCs (identified as Lin(-) c-Kit(+) Sca-1(+) IL-7Rα(-) [LKS] cells) toward macrophages (Mph), through a myeloid differentiation factor 88 (MyD88)-dependent pathway. In order to investigate the possible direct interaction of soluble microorganism-associated molecular patterns and TLRs on HSPCs in vivo, we designed a new experimental approach: purified Lin(-) and LKS cells from bone marrow of B6Ly5.1 mice (CD45.1 alloantigen) were transplanted into TLR2(-/-) , TLR4(-/-) , or MyD88(-/-) mice (CD45.2 alloantigen), which were then injected with soluble TLR ligands (Pam3CSK4, LPS, or ODN, respectively). As recipient mouse cells do not recognize the TLR ligands injected, interference by soluble mediators secreted by recipient cells is negligible. Transplanted cells were detected in the spleen and bone marrow of recipient mice, and in response to soluble TLR ligands, cells differentiated preferentially to Mph. These results show, for the first time, that HSPCs may be directly stimulated by TLR agonists in vivo, and that the engagement of these receptors induces differentiation toward Mph. Therefore, HSPCs may sense pathogen or pathogen-derived products directly during infection, inducing a rapid generation of cells of the innate immune system. Copyright © 2012 AlphaMed Press.

Super-resolution imaging using multi- electrode CMUTs: theoretical design and simulation using point targets.

PubMed

You, Wei; Cretu, Edmond; Rohling, Robert

2013-11-01

This paper investigates a low computational cost, super-resolution ultrasound imaging method that leverages the asymmetric vibration mode of CMUTs. Instead of focusing on the broadband received signal on the entire CMUT membrane, we utilize the differential signal received on the left and right part of the membrane obtained by a multi-electrode CMUT structure. The differential signal reflects the asymmetric vibration mode of the CMUT cell excited by the nonuniform acoustic pressure field impinging on the membrane, and has a resonant component in immersion. To improve the resolution, we propose an imaging method as follows: a set of manifold matrices of CMUT responses for multiple focal directions are constructed off-line with a grid of hypothetical point targets. During the subsequent imaging process, the array sequentially steers to multiple angles, and the amplitudes (weights) of all hypothetical targets at each angle are estimated in a maximum a posteriori (MAP) process with the manifold matrix corresponding to that angle. Then, the weight vector undergoes a directional pruning process to remove the false estimation at other angles caused by the side lobe energy. Ultrasound imaging simulation is performed on ring and linear arrays with a simulation program adapted with a multi-electrode CMUT structure capable of obtaining both average and differential received signals. Because the differential signals from all receiving channels form a more distinctive temporal pattern than the average signals, better MAP estimation results are expected than using the average signals. The imaging simulation shows that using differential signals alone or in combination with the average signals produces better lateral resolution than the traditional phased array or using the average signals alone. This study is an exploration into the potential benefits of asymmetric CMUT responses for super-resolution imaging.

Coral thermal tolerance: tuning gene expression to resist thermal stress.

PubMed

Bellantuono, Anthony J; Granados-Cifuentes, Camila; Miller, David J; Hoegh-Guldberg, Ove; Rodriguez-Lanetty, Mauricio

2012-01-01

The acclimatization capacity of corals is a critical consideration in the persistence of coral reefs under stresses imposed by global climate change. The stress history of corals plays a role in subsequent response to heat stress, but the transcriptomic changes associated with these plastic changes have not been previously explored. In order to identify host transcriptomic changes associated with acquired thermal tolerance in the scleractinian coral Acropora millepora, corals preconditioned to a sub-lethal temperature of 3°C below bleaching threshold temperature were compared to both non-preconditioned corals and untreated controls using a cDNA microarray platform. After eight days of hyperthermal challenge, conditions under which non-preconditioned corals bleached and preconditioned corals (thermal-tolerant) maintained Symbiodinium density, a clear differentiation in the transcriptional profiles was revealed among the condition examined. Among these changes, nine differentially expressed genes separated preconditioned corals from non-preconditioned corals, with 42 genes differentially expressed between control and preconditioned treatments, and 70 genes between non-preconditioned corals and controls. Differentially expressed genes included components of an apoptotic signaling cascade, which suggest the inhibition of apoptosis in preconditioned corals. Additionally, lectins and genes involved in response to oxidative stress were also detected. One dominant pattern was the apparent tuning of gene expression observed between preconditioned and non-preconditioned treatments; that is, differences in expression magnitude were more apparent than differences in the identity of genes differentially expressed. Our work revealed a transcriptomic signature underlying the tolerance associated with coral thermal history, and suggests that understanding the molecular mechanisms behind physiological acclimatization would be critical for the modeling of reefs in impending climate change scenarios.

Coral Thermal Tolerance: Tuning Gene Expression to Resist Thermal Stress

PubMed Central

Bellantuono, Anthony J.; Granados-Cifuentes, Camila; Miller, David J.; Hoegh-Guldberg, Ove; Rodriguez-Lanetty, Mauricio

2012-01-01

The acclimatization capacity of corals is a critical consideration in the persistence of coral reefs under stresses imposed by global climate change. The stress history of corals plays a role in subsequent response to heat stress, but the transcriptomic changes associated with these plastic changes have not been previously explored. In order to identify host transcriptomic changes associated with acquired thermal tolerance in the scleractinian coral Acropora millepora, corals preconditioned to a sub-lethal temperature of 3°C below bleaching threshold temperature were compared to both non-preconditioned corals and untreated controls using a cDNA microarray platform. After eight days of hyperthermal challenge, conditions under which non-preconditioned corals bleached and preconditioned corals (thermal-tolerant) maintained Symbiodinium density, a clear differentiation in the transcriptional profiles was revealed among the condition examined. Among these changes, nine differentially expressed genes separated preconditioned corals from non-preconditioned corals, with 42 genes differentially expressed between control and preconditioned treatments, and 70 genes between non-preconditioned corals and controls. Differentially expressed genes included components of an apoptotic signaling cascade, which suggest the inhibition of apoptosis in preconditioned corals. Additionally, lectins and genes involved in response to oxidative stress were also detected. One dominant pattern was the apparent tuning of gene expression observed between preconditioned and non-preconditioned treatments; that is, differences in expression magnitude were more apparent than differences in the identity of genes differentially expressed. Our work revealed a transcriptomic signature underlying the tolerance associated with coral thermal history, and suggests that understanding the molecular mechanisms behind physiological acclimatization would be critical for the modeling of reefs in impending climate change scenarios. PMID:23226355

Characterization of stress-responsive lncRNAs in Arabidopsis thaliana by integrating expression, epigenetic and structural features.

PubMed

Di, Chao; Yuan, Jiapei; Wu, Yue; Li, Jingrui; Lin, Huixin; Hu, Long; Zhang, Ting; Qi, Yijun; Gerstein, Mark B; Guo, Yan; Lu, Zhi John

2014-12-01

Recently, in addition to poly(A)+ long non-coding RNAs (lncRNAs), many lncRNAs without poly(A) tails, have been characterized in mammals. However, the non-polyA lncRNAs and their conserved motifs, especially those associated with environmental stresses, have not been fully investigated in plant genomes. We performed poly(A)- RNA-seq for seedlings of Arabidopsis thaliana under four stress conditions, and predicted lncRNA transcripts. We classified the lncRNAs into three confidence levels according to their expression patterns, epigenetic signatures and RNA secondary structures. Then, we further classified the lncRNAs to poly(A)+ and poly(A)- transcripts. Compared with poly(A)+ lncRNAs and coding genes, we found that poly(A)- lncRNAs tend to have shorter transcripts and lower expression levels, and they show significant expression specificity in response to stresses. In addition, their differential expression is significantly enriched in drought condition and depleted in heat condition. Overall, we identified 245 poly(A)+ and 58 poly(A)- lncRNAs that are differentially expressed under various stress stimuli. The differential expression was validated by qRT-PCR, and the signaling pathways involved were supported by specific binding of transcription factors (TFs), phytochrome-interacting factor 4 (PIF4) and PIF5. Moreover, we found many conserved sequence and structural motifs of lncRNAs from different functional groups (e.g. a UUC motif responding to salt and a AU-rich stem-loop responding to cold), indicated that the conserved elements might be responsible for the stress-responsive functions of lncRNAs. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

The startle paradigm in a forensic psychiatric setting: elucidating psychopathy.

PubMed

Loomans, Max M; Tulen, Joke H M; van Marle, Hjalmar J C

2015-02-01

Most people who meet the diagnostic criteria for anti-social personality disorder (ASPD) do not meet the criteria for psychopathy. A differentiating feature is affective-interpersonal style. Eye blink startle reflex paradigms have been used to study affect. The aim of this study is to explore an eye blink startle paradigm as a means of distinguishing between men with both ASPD and psychopathy, and men with ASPD alone. One hundred and thirty-six men were recruited as follows: 31 patients with ASPD and a Psychopathy Checklist-Revised (PCL-R) score of 26 or more, 22 patients with ASPD and a PCL-R score of 25 or less, 50 forensic hospital employees and 33 general population men, none in the latter two groups having abnormal personality traits. Each was presented with 16 pleasant, 16 unpleasant and 16 neutral pictures. Acoustic probes were presented during each category at 300, 800, 1300 and 3800 milliseconds (ms) after picture onset. Eye blink response was measured by electromyography. Overall, both patient groups showed significantly smaller eye blink responses to the startle stimuli compared with the community controls. Both the latter and the ASPD group showed the expected increase in eye blink response at longer startle latencies to unpleasant pictures than pleasant pictures, but this was not present either in the group with psychopathy or in the forensic hospital employees. With increasing startle latency onset, eye blink amplitude increased significantly in both the healthy comparison groups and the ASPD group, but not in the group with psychopathy. We replicated eye blink startle modulation deficiencies among men with psychopathy. We confirmed that the psychopathy and ASPD groups could be distinguished by startle stimulus onset asynchrony, but this pattern was also seen in one healthy group - the forensic hospital employees. This suggests a case for more research with more diverse comparison groups and more differentiation of personality traits before drawing definitive conclusions about distinctive startle response patterns among men with psychopathy. Copyright © 2014 John Wiley & Sons, Ltd.

Sphingomonas wittichii Strain RW1 Genome-Wide Gene Expression Shifts in Response to Dioxins and Clay

PubMed Central

Tsoi, Tamara V.; Iwai, Shoko; Liu, Cun; Fish, Jordan A.; Gu, Cheng; Johnson, Timothy A.; Zylstra, Gerben; Teppen, Brian J.; Li, Hui; Hashsham, Syed A.; Boyd, Stephen A.; Cole, James R.; Tiedje, James M.

2016-01-01

Sphingomonas wittichii strain RW1 (RW1) is one of the few strains that can grow on dibenzo-p-dioxin (DD). We conducted a transcriptomic study of RW1 using RNA-Seq to outline transcriptional responses to DD, dibenzofuran (DF), and the smectite clay mineral saponite with succinate as carbon source. The ability to grow on DD is rare compared to growth on the chemically similar DF even though the same initial dioxygenase may be involved in oxidation of both substrates. Therefore, we hypothesized the reason for this lies beyond catabolic pathways and may concern genes involved in processes for cell-substrate interactions such as substrate recognition, transport, and detoxification. Compared to succinate (SUC) as control carbon source, DF caused over 240 protein-coding genes to be differentially expressed, whereas more than 300 were differentially expressed with DD. Stress response genes were up-regulated in response to both DD and DF. This effect was stronger with DD than DF, suggesting a higher toxicity of DD compared to DF. Both DD and DF caused changes in expression of genes involved in active cross-membrane transport such as TonB-dependent receptor proteins, but the patterns of change differed between the two substrates. Multiple transcription factor genes also displayed expression patterns distinct to DD and DF growth. DD and DF induced the catechol ortho- and the salicylate/gentisate pathways, respectively. Both DD and DF induced the shared down-stream aliphatic intermediate compound pathway. Clay caused category-wide down-regulation of genes for cell motility and chemotaxis, particularly those involved in the synthesis, assembly and functioning of flagella. This is an environmentally important finding because clay is a major component of soil microbes’ microenvironment influencing local chemistry and may serve as a geosorbent for toxic pollutants. Similar to clay, DD and DF also affected expression of genes involved in motility and chemotaxis. PMID:27309357

Differential gene expression between skin and cervix induced by the E7 oncoprotein in a transgenic mouse model

PubMed Central

Ibarra Sierra, E; Díaz Chávez, J; Cortés-Malagón, EM; Uribe-Figueroa, L; Hidalgo-Miranda, A; Lambert, PF; Gariglio, P

2013-01-01

HPV16 E7 oncoprotein expression in K14E7 transgenic mice induces cervical cancer after 6 months of treatment with the co-carcinogen 17β-estradiol. In untreated mice, E7 also induces skin tumors late in life albeit at low penetrance. These findings indicate that E7 alters cellular functions in cervix and skin so as to predispose these organs to tumorigenesis. Using microarrays, we determined the global genes expression profile in cervical and skin tissue of young adult K14E7 transgenic mice without estrogen treatment. In these tissues, the E7 oncoprotein altered the transcriptional pattern of genes involved in several biological processes including signal transduction, transport, metabolic process, cell adhesion, apoptosis, cell differentiation, immune response and inflammatory response. Among the E7-dysregulated genes were ones not previously known to be involved in cervical neoplasia including DMBT1, GLI1 and 17βHSD2 in cervix, as well as MMP2, 12, 14, 19 and 27 in skin. PMID:22980503

Differential gene expression between skin and cervix induced by the E7 oncoprotein in a transgenic mouse model.

PubMed

Ibarra Sierra, E; Díaz Chávez, J; Cortés-Malagón, E M; Uribe-Figueroa, L; Hidalgo-Miranda, A; Lambert, P F; Gariglio, P

2012-11-25

HPV16 E7 oncoprotein expression in K14E7 transgenic mice induces cervical cancer after 6 months of treatment with the co-carcinogen 17β-estradiol. In untreated mice, E7 also induces skin tumors late in life albeit at low penetrance. These findings indicate that E7 alters cellular functions in cervix and skin so as to predispose these organs to tumorigenesis. Using microarrays, we determined the global genes expression profile in cervical and skin tissue of young adult K14E7 transgenic mice without estrogen treatment. In these tissues, the E7 oncoprotein altered the transcriptional pattern of genes involved in several biological processes including signal transduction, transport, metabolic process, cell adhesion, apoptosis, cell differentiation, immune response and inflammatory response. Among the E7-dysregulated genes were ones not previously known to be involved in cervical neoplasia including DMBT1, GLI1 and 17βHSD2 in cervix, as well as MMP2, 12, 14, 19 and 27 in skin. Copyright © 2012 Elsevier Inc. All rights reserved.

Human NOD2 Recognizes Structurally Unique Muramyl Dipeptides from Mycobacterium leprae.

PubMed

Schenk, Mirjam; Mahapatra, Sebabrata; Le, Phuonganh; Kim, Hee Jin; Choi, Aaron W; Brennan, Patrick J; Belisle, John T; Modlin, Robert L

2016-09-01

The innate immune system recognizes microbial pathogens via pattern recognition receptors. One such receptor, NOD2, via recognition of muramyl dipeptide (MDP), triggers a distinct network of innate immune responses, including the production of interleukin-32 (IL-32), which leads to the differentiation of monocytes into dendritic cells (DC). NOD2 has been implicated in the pathogenesis of human leprosy, yet it is not clear whether Mycobacterium leprae, which has a distinct MDP structure, can activate this pathway. We investigated the effect of MDP structure on the innate immune response, finding that infection of monocytes with M. leprae induces IL-32 and DC differentiation in a NOD2-dependent manner. The presence of the proximal l-Ala instead of Gly in the common configuration of the peptide side chain of M. leprae did not affect recognition by NOD2 or cytokine production. Furthermore, amidation of the d-Glu residue did not alter NOD2 activation. These data provide experimental evidence that NOD2 recognizes naturally occurring structural variants of MDP. Copyright © 2016 Schenk et al.

Child effortful control as a mediator of parenting practices on externalizing behavior: evidence for a sex-differentiated pathway across the transition from preschool to school.

PubMed

Chang, Hyein; Olson, Sheryl L; Sameroff, Arnold J; Sexton, Holly R

2011-01-01

An explanatory model for children's development of disruptive behavior across the transition from preschool to school was tested. It was hypothesized that child effortful control would mediate the effects of parenting on children's externalizing behavior and that child sex would moderate these relations. Participants were 241 children (123 boys) and their parents and teachers. Three dimensions of parenting, warm responsiveness, induction, and corporal punishment, were assessed via maternal report when children were 3 years old. Child effortful control at age 3 was measured using laboratory tasks and a mother-report questionnaire. Mothers and teachers contributed ratings of child externalizing behavior at age 6. Results showed that the hypothesized model fit the data well and that the pattern of associations between constructs differed for boys and girls. For boys, parental warm responsiveness and corporal punishment had significant indirect effects on children's externalizing behavior three years later, mediated by child effortful control. Such relations were not observed for girls. These findings support a sex-differentiated pathway to externalizing behavior across the transition from preschool to school.