Compassion: an evolutionary analysis and empirical review.

PubMed

Goetz, Jennifer L; Keltner, Dacher; Simon-Thomas, Emiliana

2010-05-01

What is compassion? And how did it evolve? In this review, we integrate 3 evolutionary arguments that converge on the hypothesis that compassion evolved as a distinct affective experience whose primary function is to facilitate cooperation and protection of the weak and those who suffer. Our empirical review reveals compassion to have distinct appraisal processes attuned to undeserved suffering; distinct signaling behavior related to caregiving patterns of touch, posture, and vocalization; and a phenomenological experience and physiological response that orients the individual to social approach. This response profile of compassion differs from those of distress, sadness, and love, suggesting that compassion is indeed a distinct emotion. We conclude by considering how compassion shapes moral judgment and action, how it varies across different cultures, and how it may engage specific patterns of neural activation, as well as emerging directions of research. (c) 2010 APA, all rights reserved.

Acute Respiratory Distress Syndrome Neutrophils Have a Distinct Phenotype and Are Resistant to Phosphoinositide 3-Kinase Inhibition

PubMed Central

Juss, Jatinder K.; House, David; Amour, Augustin; Begg, Malcolm; Herre, Jurgen; Storisteanu, Daniel M. L.; Hoenderdos, Kim; Bradley, Glyn; Lennon, Mark; Summers, Charlotte; Hessel, Edith M.; Condliffe, Alison

2016-01-01

Rationale: Acute respiratory distress syndrome is refractory to pharmacological intervention. Inappropriate activation of alveolar neutrophils is believed to underpin this disease’s complex pathophysiology, yet these cells have been little studied. Objectives: To examine the functional and transcriptional profiles of patient blood and alveolar neutrophils compared with healthy volunteer cells, and to define their sensitivity to phosphoinositide 3-kinase inhibition. Methods: Twenty-three ventilated patients underwent bronchoalveolar lavage. Alveolar and blood neutrophil apoptosis, phagocytosis, and adhesion molecules were quantified by flow cytometry, and oxidase responses were quantified by chemiluminescence. Cytokine and transcriptional profiling were used in multiplex and GeneChip arrays. Measurements and Main Results: Patient blood and alveolar neutrophils were distinct from healthy circulating cells, with increased CD11b and reduced CD62L expression, delayed constitutive apoptosis, and primed oxidase responses. Incubating control cells with disease bronchoalveolar lavage recapitulated the aberrant functional phenotype, and this could be reversed by phosphoinositide 3-kinase inhibitors. In contrast, the prosurvival phenotype of patient cells was resistant to phosphoinositide 3-kinase inhibition. RNA transcriptomic analysis revealed modified immune, cytoskeletal, and cell death pathways in patient cells, aligning closely to sepsis and burns datasets but not to phosphoinositide 3-kinase signatures. Conclusions: Acute respiratory distress syndrome blood and alveolar neutrophils display a distinct primed prosurvival profile and transcriptional signature. The enhanced respiratory burst was phosphoinositide 3-kinase–dependent but delayed apoptosis and the altered transcriptional profile were not. These unexpected findings cast doubt over the utility of phosphoinositide 3-kinase inhibition in acute respiratory distress syndrome and highlight the importance of evaluating novel therapeutic strategies in patient-derived cells. PMID:27064380

Physiological responses to fluctuating temperatures are characterized by distinct transcriptional profiles in a solitary bee

USDA-ARS?s Scientific Manuscript database

Exposure to stressful, low temperatures during development can result in the accumulation of deleterious physiological effects called chill injury. Metabolic imbalances, disruptions in ion homeostasis, and oxidative stress contribute to the increased mortality of chill-injured insects. Interestingly...

Metabolite profiling stratifies pancreatic ductal adenocarcinomas into subtypes with distinct sensitivities to metabolic inhibitors

PubMed Central

Daemen, Anneleen; Peterson, David; Sahu, Nisebita; McCord, Ron; Du, Xiangnan; Liu, Bonnie; Kowanetz, Katarzyna; Hong, Rebecca; Moffat, John; Gao, Min; Boudreau, Aaron; Mroue, Rana; Corson, Laura; O’Brien, Thomas; Qing, Jing; Sampath, Deepak; Merchant, Mark; Yauch, Robert; Manning, Gerard; Settleman, Jeffrey; Hatzivassiliou, Georgia; Evangelista, Marie

2015-01-01

Although targeting cancer metabolism is a promising therapeutic strategy, clinical success will depend on an accurate diagnostic identification of tumor subtypes with specific metabolic requirements. Through broad metabolite profiling, we successfully identified three highly distinct metabolic subtypes in pancreatic ductal adenocarcinoma (PDAC). One subtype was defined by reduced proliferative capacity, whereas the other two subtypes (glycolytic and lipogenic) showed distinct metabolite levels associated with glycolysis, lipogenesis, and redox pathways, confirmed at the transcriptional level. The glycolytic and lipogenic subtypes showed striking differences in glucose and glutamine utilization, as well as mitochondrial function, and corresponded to differences in cell sensitivity to inhibitors of glycolysis, glutamine metabolism, lipid synthesis, and redox balance. In PDAC clinical samples, the lipogenic subtype associated with the epithelial (classical) subtype, whereas the glycolytic subtype strongly associated with the mesenchymal (QM-PDA) subtype, suggesting functional relevance in disease progression. Pharmacogenomic screening of an additional ∼200 non-PDAC cell lines validated the association between mesenchymal status and metabolic drug response in other tumor indications. Our findings highlight the utility of broad metabolite profiling to predict sensitivity of tumors to a variety of metabolic inhibitors. PMID:26216984

Evidence of drug-response heterogeneity rapidly generated from a single cancer cell.

PubMed

Wang, Rong; Jin, Chengmeng; Hu, Xun

2017-06-20

One cancer cell line is believed to be composed of numerous clones with different drug sensitivity. We sought to investigate the difference of drug-response pattern in clones from a cell line or from a single cell. We showed that 22 clones derived from 4T1 cells were drastically different from each other with respect to drug-response pattern against 11 anticancer drugs and expression profile of 19 genes associated with drug resistance or sensitivity. Similar results were obtained using daughter clones derived from a single 4T1 cell. Each daughter clone showed distinct drug-response pattern and gene expression profile. Similar results were also obtained using Bcap37 cells. We conclude that a single cancer cell can rapidly produce a population of cells with high heterogeneity of drug response and the acquisition of drug-response heterogeneity is random.

Knowing where is different from knowing what: Distinct response time profiles and accuracy effects for target location, orientation, and color probability.

PubMed

Jabar, Syaheed B; Filipowicz, Alex; Anderson, Britt

2017-11-01

When a location is cued, targets appearing at that location are detected more quickly. When a target feature is cued, targets bearing that feature are detected more quickly. These attentional cueing effects are only superficially similar. More detailed analyses find distinct temporal and accuracy profiles for the two different types of cues. This pattern parallels work with probability manipulations, where both feature and spatial probability are known to affect detection accuracy and reaction times. However, little has been done by way of comparing these effects. Are probability manipulations on space and features distinct? In a series of five experiments, we systematically varied spatial probability and feature probability along two dimensions (orientation or color). In addition, we decomposed response times into initiation and movement components. Targets appearing at the probable location were reported more quickly and more accurately regardless of whether the report was based on orientation or color. On the other hand, when either color probability or orientation probability was manipulated, response time and accuracy improvements were specific for that probable feature dimension. Decomposition of the response time benefits demonstrated that spatial probability only affected initiation times, whereas manipulations of feature probability affected both initiation and movement times. As detection was made more difficult, the two effects further diverged, with spatial probability disproportionally affecting initiation times and feature probability disproportionately affecting accuracy. In conclusion, all manipulations of probability, whether spatial or featural, affect detection. However, only feature probability affects perceptual precision, and precision effects are specific to the probable attribute.

Facets of Pejorative Self-Processing in Complicated Grief

ERIC Educational Resources Information Center

Golden, Ann-Marie J.; Dalgleish, Tim

2012-01-01

Objective: Complicated grief (CG) has been proposed as a psychiatric response to bereavement distinct from established mood and anxiety disorder diagnoses. Little is known about the nature of cognitive-affective processing in CG, nor any similarities or differences compared with the processing profiles associated with other emotional disorders.…

Rat Models of Cardiovascular Disease Demonstrate Distinctive Pulmonary Gene Expressions for Vascular Response Genes: Impact of Ozone Exposure

EPA Science Inventory

Comparative gene expression profiling of multiple tissues from rat strains with genetic predisposition to diverse cardiovascular diseases (CVD) can help decode the transcriptional program that governs organ-specific functions. We examined expressions of CVD genes in the lungs of ...

Primary EBV Infection Induces an Expression Profile Distinct from Other Viruses but Similar to Hemophagocytic Syndromes

PubMed Central

Dunmire, Samantha K.; Odumade, Oludare A.; Porter, Jean L.; Reyes-Genere, Juan; Schmeling, David O.; Bilgic, Hatice; Fan, Danhua; Baechler, Emily C.; Balfour, Henry H.; Hogquist, Kristin A.

2014-01-01

Epstein-Barr Virus (EBV) causes infectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. Transcriptome analysis defined a striking and reproducible expression profile during acute infection but no lasting gene changes were apparent during latent infection. Comparing the EBV response profile to multiple other acute viral infections, including influenza A (influenza), respiratory syncytial virus (RSV), human rhinovirus (HRV), attenuated yellow fever virus (YFV), and Dengue fever virus (DENV), revealed similarity only to DENV. The signature shared by EBV and DENV was also present in patients with hemophagocytic syndromes, suggesting these two viruses cause uncontrolled inflammatory responses. Interestingly, while EBV induced a strong type I interferon response, a subset of interferon induced genes, including MX1, HERC5, and OAS1, were not upregulated, suggesting a mechanism by which viral antagonism of immunity results in a profound inflammatory response. These data provide an important first description of the response to a natural herpesvirus infection in humans. PMID:24465555

Primary EBV infection induces an expression profile distinct from other viruses but similar to hemophagocytic syndromes.

PubMed

Dunmire, Samantha K; Odumade, Oludare A; Porter, Jean L; Reyes-Genere, Juan; Schmeling, David O; Bilgic, Hatice; Fan, Danhua; Baechler, Emily C; Balfour, Henry H; Hogquist, Kristin A

2014-01-01

Epstein-Barr Virus (EBV) causes infectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. Transcriptome analysis defined a striking and reproducible expression profile during acute infection but no lasting gene changes were apparent during latent infection. Comparing the EBV response profile to multiple other acute viral infections, including influenza A (influenza), respiratory syncytial virus (RSV), human rhinovirus (HRV), attenuated yellow fever virus (YFV), and Dengue fever virus (DENV), revealed similarity only to DENV. The signature shared by EBV and DENV was also present in patients with hemophagocytic syndromes, suggesting these two viruses cause uncontrolled inflammatory responses. Interestingly, while EBV induced a strong type I interferon response, a subset of interferon induced genes, including MX1, HERC5, and OAS1, were not upregulated, suggesting a mechanism by which viral antagonism of immunity results in a profound inflammatory response. These data provide an important first description of the response to a natural herpesvirus infection in humans.

Identifying patterns of motor performance, executive functioning, and verbal ability in preschool children: A latent profile analysis.

PubMed

Houwen, Suzanne; Kamphorst, Erica; van der Veer, Gerda; Cantell, Marja

2018-04-30

A relationship between motor performance and cognitive functioning is increasingly being recognized. Yet, little is known about the precise nature of the relationship between both domains, especially in early childhood. To identify distinct constellations of motor performance, executive functioning (EF), and verbal ability in preschool aged children; and to explore how individual and contextual variables are related to profile membership. The sample consisted of 119 3- to 4-year old children (62 boys; 52%). The home based assessments consisted of a standardized motor test (Movement Assessment Battery for Children - 2), five performance-based EF tasks measuring inhibition and working memory, and the Receptive Vocabulary subtest from the Wechsler Preschool and Primary Scale of Intelligence Third Edition. Parents filled out the Behavior Rating Inventory of Executive Function - Preschool version. Latent profile analysis (LPA) was used to delineate profiles of motor performance, EF, and verbal ability. Chi-square statistics and multinomial logistic regression analysis were used to examine whether profile membership was predicted by age, gender, risk of motor coordination difficulties, ADHD symptomatology, language problems, and socioeconomic status (SES). LPA yielded three profiles with qualitatively distinct response patterns of motor performance, EF, and verbal ability. Quantitatively, the profiles showed most pronounced differences with regard to parent ratings and performance-based tests of EF, as well as verbal ability. Risk of motor coordination difficulties and ADHD symptomatology were associated with profile membership, whereas age, gender, language problems, and SES were not. Our results indicate that there are distinct subpopulations of children who show differential relations with regard to motor performance, EF, and verbal ability. The fact that we found both quantitative as well as qualitative differences between the three patterns of profiles underscores the need for a person-centered approach with a focus on patterns of individual characteristics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genome-Wide Requirements for Resistance to Functionally Distinct DNA-Damaging Agents

PubMed Central

Proctor, Michael; Flaherty, Patrick; Jordan, Michael I; Arkin, Adam P; Davis, Ronald W; Nislow, Corey; Giaever, Guri

2005-01-01

The mechanistic and therapeutic differences in the cellular response to DNA-damaging compounds are not completely understood, despite intense study. To expand our knowledge of DNA damage, we assayed the effects of 12 closely related DNA-damaging agents on the complete pool of ~4,700 barcoded homozygous deletion strains of Saccharomyces cerevisiae. In our protocol, deletion strains are pooled together and grown competitively in the presence of compound. Relative strain sensitivity is determined by hybridization of PCR-amplified barcodes to an oligonucleotide array carrying the barcode complements. These screens identified genes in well-characterized DNA-damage-response pathways as well as genes whose role in the DNA-damage response had not been previously established. High-throughput individual growth analysis was used to independently confirm microarray results. Each compound produced a unique genome-wide profile. Analysis of these data allowed us to determine the relative importance of DNA-repair modules for resistance to each of the 12 profiled compounds. Clustering the data for 12 distinct compounds uncovered both known and novel functional interactions that comprise the DNA-damage response and allowed us to define the genetic determinants required for repair of interstrand cross-links. Further genetic analysis allowed determination of epistasis for one of these functional groups. PMID:16121259

Investigation of sensory profiles and hedonic drivers of emerging aquaculture fish species.

PubMed

Alexi, Niki; Byrne, Derek V; Nanou, Evangelia; Grigorakis, Kriton

2018-02-01

The aquaculture sector needs to increase the diversity fish species and their processed products to cover rising consumer demands. Candidates for this diversification have been identified to be meagre, greater amberjack, pikeperch and wreckfish. Yet scientific knowledge on their sensory profiles and consumer hedonic responses is scarce. The aim of the current study was to investigate these aspects, since they are essential for product development and market targeting. Species exhibited different sensory profiles with the exception of the odor/flavor profiles of meagre and greater amberjack, which were similar. Texture was more important than odor/flavor in explaining interspecies differences. Yet the hedonic responses were equally related to texture and odor/flavor. None of the species received negative hedonic scores. Both positive and negative hedonic drivers were identified within the odor/flavor and texture modalities. The distinct profiles of meagre, greater amberjack, pikeperch and wreckfish make these fish species valuable first materials for new product development and for covering markets with different sensory preferences. Differences in fish texture are more easily perceivable, yet small variations in fish odor/flavor can have a great impact on consumers' hedonic responses. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

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

PubMed Central

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

2014-01-01

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

Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination

PubMed Central

Fourati, Slim; Cristescu, Razvan; Loboda, Andrey; Talla, Aarthi; Filali, Ali; Railkar, Radha; Schaeffer, Andrea K.; Favre, David; Gagnon, Dominic; Peretz, Yoav; Wang, I-Ming; Beals, Chan R.; Casimiro, Danilo R.; Carayannopoulos, Leonidas N.; Sékaly, Rafick-Pierre

2016-01-01

Aging is associated with hyporesponse to vaccination, whose mechanisms remain unclear. In this study hepatitis B virus (HBV)-naive older adults received three vaccines, including one against HBV. Here we show, using transcriptional and cytometric profiling of whole blood collected before vaccination, that heightened expression of genes that augment B-cell responses and higher memory B-cell frequencies correlate with stronger responses to HBV vaccine. In contrast, higher levels of inflammatory response transcripts and increased frequencies of pro-inflammatory innate cells correlate with weaker responses to this vaccine. Increased numbers of erythrocytes and the haem-induced response also correlate with poor response to the HBV vaccine. A transcriptomics-based pre-vaccination predictor of response to HBV vaccine is built and validated in distinct sets of older adults. This moderately accurate (area under the curve≈65%) but robust signature is supported by flow cytometry and cytokine profiling. This study is the first that identifies baseline predictors and mechanisms of response to the HBV vaccine. PMID:26742691

MicroRNA Profiling Reveals Marker of Motor Neuron Disease in ALS Models.

PubMed

Hoye, Mariah L; Koval, Erica D; Wegener, Amy J; Hyman, Theodore S; Yang, Chengran; O'Brien, David R; Miller, Rebecca L; Cole, Tracy; Schoch, Kathleen M; Shen, Tao; Kunikata, Tomonori; Richard, Jean-Philippe; Gutmann, David H; Maragakis, Nicholas J; Kordasiewicz, Holly B; Dougherty, Joseph D; Miller, Timothy M

2017-05-31

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. microRNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining the in vivo miRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents. SIGNIFICANCE STATEMENT Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain and spinal cord are selectively lost. To develop tools to aid in our understanding of the distinct expression profiles of MNs and, ultimately, to monitor MN disease progression, we identified small regulatory microRNAs (miRNAs) that were highly enriched or exclusive in MNs. The signal for one of these MN-enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where its levels change as disease progresses, suggesting that it may be a clinically useful marker of disease status. Furthermore, rats treated with ALS therapy have restored expression of this MN RNA marker, making it an MN-specific and drug-responsive marker for ALS rodents. Copyright © 2017 the authors 0270-6474/17/375574-13$15.00/0.

Molecular Markers in Patients with Chronic Wounds to Guide Surgical Debridement

PubMed Central

Brem, Harold; Stojadinovic, Olivera; Diegelmann, Robert F; Entero, Hyacinth; Lee, Brian; Pastar, Irena; Golinko, Michael; Rosenberg, Harvey; Tomic-Canic, Marjana

2007-01-01

Chronic wounds, such as venous ulcers, are characterized by physiological impairments manifested by delays in healing, resulting in severe morbidity. Surgical debridement is routinely performed on chronic wounds because it stimulates healing. However, procedures are repeated many times on the same patient because, in contrast to tumor excision, there are no objective biological/molecular markers to guide the extent of debridement. To develop bioassays that can potentially guide surgical debridement, we assessed the pathogenesis of the patients’ wound tissue before and after wound debridement. We obtained biopsies from three patients at two locations, the nonhealing edge (prior to debridement) and the adjacent, nonulcerated skin of the venous ulcers (post debridement), and evaluated their histology, biological response to wounding (migration) and gene expression profile. We found that biopsies from the nonhealing edges exhibit distinct pathogenic morphology (hyperproliferative/hyperkeratotic epidermis; dermal fibrosis; increased procollagen synthesis). Fibroblasts deriving from this location exhibit impaired migration in comparison to the cells from adjacent nonulcerated biopsies, which exhibit normalization of morphology and normal migration capacity. The nonhealing edges have a specific, identifiable, and reproducible gene expression profile. The adjacent nonulcerated biopsies have their own distinctive reproducible gene expression profile, signifying that particular wound areas can be identified by gene expression profiling. We conclude that chronic ulcers contain distinct subpopulations of cells with different capacity to heal and that gene expression profiling can be utilized to identify them. In the future, molecular markers will be developed to identify the nonimpaired tissue, thereby making surgical debridement more accurate and more efficacious. PMID:17515955

Mutagen Structure and Transcriptional Response: Induction of Distinct Transcriptional Profiles in Salmonella TA100 by the Drinking-Water Mutagen MX and Its Homologues

EPA Science Inventory

The relationship between chemical structure and biological activity has been examined for various compounds and endpoints for decades. To explore this question relative to global gene expression, we performed microarray analysis of Salmonella TA100 after treatment under condition...

Behçet's: A Disease or a Syndrome? Answer from an Expression Profiling Study.

PubMed

Oğuz, Ali Kemal; Yılmaz, Seda Taşır; Oygür, Çağdaş Şahap; Çandar, Tuba; Sayın, Irmak; Kılıçoğlu, Sibel Serin; Ergün, İhsan; Ateş, Aşkın; Özdağ, Hilal; Akar, Nejat

2016-01-01

Behçet's disease (BD) is a chronic, relapsing, multisystemic inflammatory disorder with unanswered questions regarding its etiology/pathogenesis and classification. Distinct manifestation based subsets, pronounced geographical variations in expression, and discrepant immunological abnormalities raised the question whether Behçet's is "a disease or a syndrome". To answer the preceding question we aimed to display and compare the molecular mechanisms underlying distinct subsets of BD. For this purpose, the expression data of the gene expression profiling and association study on BD by Xavier et al (2013) was retrieved from GEO database and reanalysed by gene expression data analysis/visualization and bioinformatics enrichment tools. There were 15 BD patients (B) and 14 controls (C). Three subsets of BD patients were generated: MB (isolated mucocutaneous manifestations, n = 7), OB (ocular involvement, n = 4), and VB (large vein thrombosis, n = 4). Class comparison analyses yielded the following numbers of differentially expressed genes (DEGs); B vs C: 4, MB vs C: 5, OB vs C: 151, VB vs C: 274, MB vs OB: 215, MB vs VB: 760, OB vs VB: 984. Venn diagram analysis showed that there were no common DEGs in the intersection "MB vs C" ∩ "OB vs C" ∩ "VB vs C". Cluster analyses successfully clustered distinct expressions of BD. During gene ontology term enrichment analyses, categories with relevance to IL-8 production (MB vs C) and immune response to microorganisms (OB vs C) were differentially enriched. Distinct subsets of BD display distinct expression profiles and different disease associated pathways. Based on these clear discrepancies, the designation as "Behçet's syndrome" (BS) should be encouraged and future research should take into consideration the immunogenetic heterogeneity of BS subsets. Four gene groups, namely, negative regulators of inflammation (CD69, CLEC12A, CLEC12B, TNFAIP3), neutrophil granule proteins (LTF, OLFM4, AZU1, MMP8, DEFA4, CAMP), antigen processing and presentation proteins (CTSS, ERAP1), and regulators of immune response (LGALS2, BCL10, ITCH, CEACAM8, CD36, IL8, CCL4, EREG, NFKBIZ, CCR2, CD180, KLRC4, NFAT5) appear to be instrumental in BS immunopathogenesis.

From loquacious to reticent: understanding patient health information communication to guide consumer health IT design.

PubMed

Valdez, Rupa S; Guterbock, Thomas M; Fitzgibbon, Kara; Williams, Ishan C; Wellbeloved-Stone, Claire A; Bears, Jaime E; Menefee, Hannah K

2017-07-01

It is increasingly recognized that some patients self-manage in the context of social networks rather than alone. Consumer health information technology (IT) designed to support socially embedded self-management must be responsive to patients' everyday communication practices. There is an opportunity to improve consumer health IT design by explicating how patients currently leverage social media to support health information communication. The objective of this study was to determine types of health information communication patterns that typify Facebook users with chronic health conditions to guide consumer health IT design. Seven hundred participants with type 2 diabetes were recruited through a commercial survey access panel. Cluster analysis was used to identify distinct approaches to health information communication both on and off Facebook. Analysis of variance (ANOVA) methods were used to identify demographic and behavioral differences among profiles. Secondary analysis of qualitative interviews ( n  = 25) and analysis of open-ended survey questions were conducted to understand participant rationales for each profile. Our analysis yielded 7 distinct health information communication profiles. Five of 7 profiles had consistent patterns both on and off Facebook, while the remaining 2 demonstrated distinct practices, with no health information communication on Facebook but some off Facebook. One profile was distinct from all others in both health information communication practices and demographic composition. Rationales for following specific health information communication practices were categorized under 6 themes: altruism, instrumental support, social support, privacy and stigma, convenience, and Facebook knowledge. Facebook has been widely adopted for health information communication; This study demonstrates that Facebook has been widely adopted for health information communication. It also shows that the ways in which patients communicate health information on and off Facebook are diverse. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Short communication: Cytokine profiles from blood mononuclear cells of dairy cows classified with divergent immune response phenotypes.

PubMed

Martin, C E; Paibomesai, M A; Emam, S M; Gallienne, J; Hine, B C; Thompson-Crispi, K A; Mallard, B A

2016-03-01

Genetic selection for enhanced immune response has been shown to decrease disease occurrence in dairy cattle. Cows can be classified as high (H), average, or low responders based on antibody-mediated immune response (AMIR), predominated by type-2 cytokine production, and cell-mediated immune response (CMIR) through estimated breeding values for these traits. The purpose of this study was to identify in vitro tests that correlate with in vivo immune response phenotyping in dairy cattle. Blood mononuclear cells (BMC) isolated from cows classified as H-AMIR and H-CMIR through estimated breeding values for immune response traits were stimulated with concanavalin A (ConA; Sigma Aldrich, St. Louis, MO) and gene expression, cytokine production, and cell proliferation was determined at multiple time points. A repeated measures model, which included the effects of immune response group, parity, and stage of lactation, was used to compare differences between immune response phenotype groups. The H-AMIR cows produced more IL-4 protein than H-CMIR cows at 48 h; however, no difference in gene expression of type-2 transcription factor GATA3 or IL4 was noted. The BMC from H-CMIR cows had increased production of IFN-γ protein at 48, 72, and 96 h compared with H-AMIR animals. Further, H-CMIR cows had increased expression of the IFNG gene at 16, 24, and 48 h post-treatment with ConA, although expression of the type-1 transcription factor gene TBX21 did not differ between immune response groups. Although proliferation of BMC increased from 24 to 72 h after ConA stimulation, no differences were found between the immune response groups. Overall, stimulation of H-AMIR and H-CMIR bovine BMC with ConA resulted in distinct cytokine production profiles according to genetically defined groups. These distinct cytokine profiles could be used to define disease resistance phenotypes in dairy cows according to stimulation in vitro; however, other immune response phenotypes should be assessed. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Comparative Expression Profiling of Distinct T Cell Subsets Undergoing Oxidative Stress

PubMed Central

Lichtenfels, Rudolf; Mougiakakos, Dimitrios; Johansson, C. Christian; Dressler, Sven P.; Recktenwald, Christian V.; Kiessling, Rolf; Seliger, Barbara

2012-01-01

The clinical outcome of adoptive T cell transfer-based immunotherapies is often limited due to different escape mechanisms established by tumors in order to evade the hosts' immune system. The establishment of an immunosuppressive micromilieu by tumor cells along with distinct subsets of tumor-infiltrating lymphocytes is often associated with oxidative stress that can affect antigen-specific memory/effector cytotoxic T cells thereby substantially reducing their frequency and functional activation. Therefore, protection of tumor-reactive cytotoxic T lymphocytes from oxidative stress may enhance the anti-tumor-directed immune response. In order to better define the key pathways/proteins involved in the response to oxidative stress a comparative 2-DE-based proteome analysis of naïve CD45RA+ and their memory/effector CD45RO+ T cell counterparts in the presence and absence of low dose hydrogen peroxide (H2O2) was performed in this pilot study. Based on the profiling data of these T cell subpopulations under the various conditions, a series of differentially expressed spots were defined, members thereof identified by mass spectrometry and subsequently classified according to their cellular function and localization. Representative targets responding to oxidative stress including proteins involved in signaling pathways, in regulating the cellular redox status as well as in shaping/maintaining the structural cell integrity were independently verified at the transcript and protein level under the same conditions in both T cell subsets. In conclusion the resulting profiling data describe complex, oxidative stress-induced, but not strictly concordant changes within the respective expression profiles of CD45RA+ and CD45RO+ T cells. Some of the differentially expressed genes/proteins might be further exploited as potential targets toward modulating the redox capacity of the distinct lymphocyte subsets thereby providing the basis for further studies aiming at rendering them more resistant to tumor micromilieu-induced oxidative stress. PMID:22911781

Selective estrogen receptor modulators in clinical practice: a safety overview.

PubMed

Ellis, Amanda J; Hendrick, Vicky M; Williams, Robert; Komm, Barry S

2015-06-01

Selective estrogen receptor (ER) modulators (SERMs) are a class of nonsteroidal compounds that interact with ERs, each with a distinct tissue-specific profile. Depending upon the degree of ER agonism/antagonism at the target tissue, SERMs show efficacy for various indications including osteoporosis, dyspareunia, and breast cancer, and are associated with safety risks. This review describes the safety profile of SERMs (tamoxifen, raloxifene, toremifene, bazedoxifene, lasofoxifene, and ospemifene) and fulvestrant (a pure ER antagonist) from Phase III trials, long-term extension studies, and active comparator studies. Tamoxifen, a first-generation SERM, is indicated for breast cancer prevention and treatment but is associated with serious safety concerns including endometrial cancer, venous thromboembolic events (VTE), and stroke. Toremifene, raloxifene, bazedoxifene, lasofoxifene, and ospemifene present generally improved, though distinctly different, safety profiles compared with tamoxifen, especially with endometrial cancer and stroke. However, the risk of VTE remains a concern for most SERMs. Each SERM presents a unique risk/benefit profile based on varying indications and tissue-specific ER agonist and antagonist effects, making careful patient selection and ongoing patient monitoring crucial aspects of treatment. Future research may focus on identifying new SERMs for endocrine-resistant and endocrine-responsive cancers and post-menopausal symptoms.

GNQ-209P Mutation in Metastatic Uveal Melanoma and Treatment Outcome.

PubMed

Abdel Karim, Nagla; Eldessouki, Ihab; Taftaf, Ahmad; Ayham, Deeb; Gaber, Ola; Makramalla, Abouelmagd; Correa, Zelia M

2018-01-01

Metastatic prognosis in uveal melanoma is assessed by gene expression profiling (GEP) testing of the tumor cells, usually obtained by fine needle aspiration (FNA). GEP has demonstrated high accuracy in distinguishing class I and II tumors, both having different metastatic potential. Transcriptomic studies identified distinct mutations including somatic mutations in GNAQ and GNA11 , detected in more than 80%, and contribute to the upregulation of the mitogen-activated protein kinase (MAPK) pathway and the development of uveal melanoma (UM). The role of these mutations in treatment selection and possible benefit from targeted therapy are somewhat unclear. However, until the discovery of novel agents, local versus systemic therapies remain options for treatment that can still be considered for disease control in certain cases. We report a series of patients with metastatic UM with distinct mutational profiles. One had significant liver metastases with proven GNQ-209P mutation on tissue biopsy while peripheral blood molecular profiling did not show these mutations. The other three cases had no GNQ-209P mutation. All cases received nab-paclitaxel (Abraxane) as a treatment drug, and we record their responses to treatment and their molecular-profiling results.

Exploring student learning profiles in algebra-based studio physics: A person-centered approach

NASA Astrophysics Data System (ADS)

Pond, Jarrad W. T.; Chini, Jacquelyn J.

2017-06-01

In this study, we explore the strategic self-regulatory and motivational characteristics of students in studio-mode physics courses at three universities with varying student populations and varying levels of success in their studio-mode courses. We survey students using questions compiled from several existing questionnaires designed to measure students' study strategies, attitudes toward and motivations for learning physics, organization of scientific knowledge, experiences outside the classroom, and demographics. Using a person-centered approach, we utilize cluster analysis methods to group students into learning profiles based on their individual responses to better understand the strategies and motives of algebra-based studio physics students. Previous studies have identified five distinct learning profiles across several student populations using similar methods. We present results from first-semester and second-semester studio-mode introductory physics courses across three universities. We identify these five distinct learning profiles found in previous studies to be present within our population of introductory physics students. In addition, we investigate interactions between these learning profiles and student demographics. We find significant interactions between a student's learning profile and their experience with high school physics, major, gender, grade expectation, and institution. Ultimately, we aim to use this method of analysis to take the characteristics of students into account in the investigation of successful strategies for using studio methods of physics instruction within and across institutions.

A unique proteomic profile on surface IgM ligation in unmutated chronic lymphocytic leukemia

PubMed Central

Perrot, Aurore; Pionneau, Cédric; Nadaud, Sophie; Davi, Frédéric; Leblond, Véronique; Jacob, Frédéric; Merle-Béral, Hélène; Herbrecht, Raoul; Béné, Marie-Christine; Gribben, John G.; Vallat, Laurent

2011-01-01

Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course with 2 extreme subsets: indolent, ZAP70− and mutated immunoglobulin heavy chain gene (M-CLL); and aggressive, ZAP70+ and unmutated immunoglobulin heavy chain (UM-CLL). Given the long-term suspicion of antigenic stimulation as a primum movens in the disease, the role of the B-cell receptor has been extensively studied in various experimental settings; albeit scarcely in a comparative dynamic proteomic approach. Here we use a quantitative 2-dimensional fluorescence difference gel electrophoresis technology to compare 48 proteomic profiles of the 2 CLL subsets before and after anti-IgM ligation. Differentially expressed proteins were subsequently identified by mass spectrometry. We show that unstimulated M- and UM-CLL cells display distinct proteomic profiles. Furthermore, anti-IgM stimulation induces a specific proteomic response, more pronounced in the more aggressive CLL. Statistical analyses demonstrate several significant protein variations according to stimulation conditions. Finally, we identify an intermediate form of M-CLL cells, with an indolent profile (ZAP70−) but sharing aggressive proteomic profiles alike UM-CLL cells. Collectively, this first quantitative and dynamic proteome analysis of CLL further dissects the complex molecular pathway after B-cell receptor stimulation and depicts distinct proteomic profiles, which could lead to novel molecular stratification of the disease. PMID:21602524

Compositionally and functionally distinct sinus microbiota in chronic rhinosinusitis patients have immunological and clinically divergent consequences.

PubMed

Cope, Emily K; Goldberg, Andrew N; Pletcher, Steven D; Lynch, Susan V

2017-05-12

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by persistent sinonasal inflammation and sinus microbiome dysbiosis. The basis of this heterogeneity is poorly understood. We sought to address the hypothesis that a limited number of compositionally distinct pathogenic bacterial microbiota exist in CRS patients and invoke discrete immune responses and clinical phenotypes in CRS patients. Sinus brushings from patients with CRS (n = 59) and healthy individuals (n = 10) collected during endoscopic sinus surgery were analyzed using 16S rRNA gene sequencing, predicted metagenomics, and RNA profiling of the mucosal immune response. We show that CRS patients cluster into distinct sub-groups (DSI-III), each defined by specific pattern of bacterial co-colonization (permutational multivariate analysis of variance (PERMANOVA); p = 0.001, r 2  = 0.318). Each sub-group was typically dominated by a pathogenic family: Streptococcaceae (DSI), Pseudomonadaceae (DSII), Corynebacteriaceae [DSIII(a)], or Staphylococcaceae [DSIII(b)]. Each pathogenic microbiota was predicted to be functionally distinct (PERMANOVA; p = 0.005, r 2  = 0.217) and encode uniquely enriched gene pathways including ansamycin biosynthesis (DSI), tryptophan metabolism (DSII), two-component response [DSIII(b)], and the PPAR-γ signaling pathway [DSIII(a)]. Each is also associated with significantly distinct host immune responses; DSI, II, and III(b) invoked a variety of pro-inflammatory, T H 1 responses, while DSIII(a), which exhibited significantly increased incidence of nasal polyps (Fisher's exact; p = 0.034, relative risk = 2.16), primarily induced IL-5 expression (Kruskal Wallis; q = 0.045). A large proportion of CRS patient heterogeneity may be explained by the composition of their sinus bacterial microbiota and related host immune response-features which may inform strategies for tailored therapy in this patient population.

Bridging the gap between high-throughput genetic and transcriptional data reveals cellular pathways responding to alpha-synuclein toxicity

PubMed Central

Yeger-Lotem, Esti; Riva, Laura; Su, Linhui Julie; Gitler, Aaron D.; Cashikar, Anil; King, Oliver D.; Auluck, Pavan K.; Geddie, Melissa L.; Valastyan, Julie S.; Karger, David R.; Lindquist, Susan; Fraenkel, Ernest

2009-01-01

Cells respond to stimuli by changes in various processes, including signaling pathways and gene expression. Efforts to identify components of these responses increasingly depend on mRNA profiling and genetic library screens, yet the functional roles of the genes identified by these assays often remain enigmatic. By comparing the results of these two assays across various cellular responses, we found that they are consistently distinct. Moreover, genetic screens tend to identify response regulators, while mRNA profiling frequently detects metabolic responses. We developed an integrative approach that bridges the gap between these data using known molecular interactions, thus highlighting major response pathways. We harnessed this approach to reveal cellular pathways related to alpha-synuclein, a small lipid-binding protein implicated in several neurodegenerative disorders including Parkinson disease. For this we screened an established yeast model for alpha-synuclein toxicity to identify genes that when overexpressed alter cellular survival. Application of our algorithm to these data and data from mRNA profiling provided functional explanations for many of these genes and revealed novel relations between alpha-synuclein toxicity and basic cellular pathways. PMID:19234470

Rhizosphere Protists Change Metabolite Profiles in Zea mays.

PubMed

Kuppardt, Anke; Fester, Thomas; Härtig, Claus; Chatzinotas, Antonis

2018-01-01

Plant growth and productivity depend on the interactions of the plant with the associated rhizosphere microbes. Rhizosphere protists play a significant role in this respect: considerable efforts have been made in the past to reveal the impact of protist-bacteria interactions on the remobilization of essential nutrients for plant uptake, or the grazing induced changes on plant-growth promoting bacteria and the root-architecture. However, the metabolic responses of plants to the presence of protists or to protist-bacteria interactions in the rhizosphere have not yet been analyzed. Here we studied in controlled laboratory experiments the impact of bacterivorous protists in the rhizosphere on maize plant growth parameters and the bacterial community composition. Beyond that we investigated the induction of plant biochemical responses by separately analyzing above- and below-ground metabolite profiles of maize plants incubated either with a soil bacterial inoculum or with a mixture of soil bacteria and bacterivorous protists. Significantly distinct leaf and root metabolite profiles were obtained from plants which grew in the presence of protists. These profiles showed decreased levels of a considerable number of metabolites typical for the plant stress reaction, such as polyols, a number of carbohydrates and metabolites connected to phenolic metabolism. We assume that this decrease in plant stress is connected to the grazing induced shifts in rhizosphere bacterial communities as shown by distinct T-RFLP community profiles. Protist grazing had a clear effect on the overall bacterial community composition, richness and evenness in our microcosms. Given the competition of plant resource allocation to either defense or growth, we propose that a reduction in plant stress levels caused directly or indirectly by protists may be an additional reason for corresponding positive effects on plant growth.

Rhizosphere Protists Change Metabolite Profiles in Zea mays

PubMed Central

Kuppardt, Anke; Fester, Thomas; Härtig, Claus; Chatzinotas, Antonis

2018-01-01

Plant growth and productivity depend on the interactions of the plant with the associated rhizosphere microbes. Rhizosphere protists play a significant role in this respect: considerable efforts have been made in the past to reveal the impact of protist-bacteria interactions on the remobilization of essential nutrients for plant uptake, or the grazing induced changes on plant-growth promoting bacteria and the root-architecture. However, the metabolic responses of plants to the presence of protists or to protist-bacteria interactions in the rhizosphere have not yet been analyzed. Here we studied in controlled laboratory experiments the impact of bacterivorous protists in the rhizosphere on maize plant growth parameters and the bacterial community composition. Beyond that we investigated the induction of plant biochemical responses by separately analyzing above- and below-ground metabolite profiles of maize plants incubated either with a soil bacterial inoculum or with a mixture of soil bacteria and bacterivorous protists. Significantly distinct leaf and root metabolite profiles were obtained from plants which grew in the presence of protists. These profiles showed decreased levels of a considerable number of metabolites typical for the plant stress reaction, such as polyols, a number of carbohydrates and metabolites connected to phenolic metabolism. We assume that this decrease in plant stress is connected to the grazing induced shifts in rhizosphere bacterial communities as shown by distinct T-RFLP community profiles. Protist grazing had a clear effect on the overall bacterial community composition, richness and evenness in our microcosms. Given the competition of plant resource allocation to either defense or growth, we propose that a reduction in plant stress levels caused directly or indirectly by protists may be an additional reason for corresponding positive effects on plant growth. PMID:29780370

Distinct functional contributions of primary sensory and association areas to audiovisual integration in object categorization.

PubMed

Werner, Sebastian; Noppeney, Uta

2010-02-17

Multisensory interactions have been demonstrated in a distributed neural system encompassing primary sensory and higher-order association areas. However, their distinct functional roles in multisensory integration remain unclear. This functional magnetic resonance imaging study dissociated the functional contributions of three cortical levels to multisensory integration in object categorization. Subjects actively categorized or passively perceived noisy auditory and visual signals emanating from everyday actions with objects. The experiment included two 2 x 2 factorial designs that manipulated either (1) the presence/absence or (2) the informativeness of the sensory inputs. These experimental manipulations revealed three patterns of audiovisual interactions. (1) In primary auditory cortices (PACs), a concurrent visual input increased the stimulus salience by amplifying the auditory response regardless of task-context. Effective connectivity analyses demonstrated that this automatic response amplification is mediated via both direct and indirect [via superior temporal sulcus (STS)] connectivity to visual cortices. (2) In STS and intraparietal sulcus (IPS), audiovisual interactions sustained the integration of higher-order object features and predicted subjects' audiovisual benefits in object categorization. (3) In the left ventrolateral prefrontal cortex (vlPFC), explicit semantic categorization resulted in suppressive audiovisual interactions as an index for multisensory facilitation of semantic retrieval and response selection. In conclusion, multisensory integration emerges at multiple processing stages within the cortical hierarchy. The distinct profiles of audiovisual interactions dissociate audiovisual salience effects in PACs, formation of object representations in STS/IPS and audiovisual facilitation of semantic categorization in vlPFC. Furthermore, in STS/IPS, the profiles of audiovisual interactions were behaviorally relevant and predicted subjects' multisensory benefits in performance accuracy.

Identification of differentially expressed genes in cucumber (Cucumis sativus L.) root under waterlogging stress by digital gene expression profile.

PubMed

Qi, Xiao-Hua; Xu, Xue-Wen; Lin, Xiao-Jian; Zhang, Wen-Jie; Chen, Xue-Hao

2012-03-01

High-throughput tag-sequencing (Tag-seq) analysis based on the Solexa Genome Analyzer platform was applied to analyze the gene expression profiling of cucumber plant at 5 time points over a 24h period of waterlogging treatment. Approximately 5.8 million total clean sequence tags per library were obtained with 143013 distinct clean tag sequences. Approximately 23.69%-29.61% of the distinct clean tags were mapped unambiguously to the unigene database, and 53.78%-60.66% of the distinct clean tags were mapped to the cucumber genome database. Analysis of the differentially expressed genes revealed that most of the genes were down-regulated in the waterlogging stages, and the differentially expressed genes mainly linked to carbon metabolism, photosynthesis, reactive oxygen species generation/scavenging, and hormone synthesis/signaling. Finally, quantitative real-time polymerase chain reaction using nine genes independently verified the tag-mapped results. This present study reveals the comprehensive mechanisms of waterlogging-responsive transcription in cucumber. Copyright © 2011 Elsevier Inc. All rights reserved.

The neural basis of emotions varies over time: different regions go with onset- and offset-bound processes underlying emotion intensity.

PubMed

Résibois, Maxime; Verduyn, Philippe; Delaveau, Pauline; Rotgé, Jean-Yves; Kuppens, Peter; Van Mechelen, Iven; Fossati, Philippe

2017-08-01

According to theories of emotion dynamics, emotions unfold across two phases in which different types of processes come to the fore: emotion onset and emotion offset. Differences in onset-bound processes are reflected by the degree of explosiveness or steepness of the response at onset, and differences in offset-bound processes by the degree of accumulation or intensification of the subsequent response. Whether onset- and offset-bound processes have distinctive neural correlates and, hence, whether the neural basis of emotions varies over time, still remains unknown. In the present fMRI study, we address this question using a recently developed paradigm that allows to disentangle explosiveness and accumulation. Thirty-one participants were exposed to neutral and negative social feedback, and asked to reflect on its contents. Emotional intensity while reading and thinking about the feedback was measured with an intensity profile tracking approach. Using non-negative matrix factorization, the resulting profile data were decomposed in explosiveness and accumulation components, which were subsequently entered as continuous regressors of the BOLD response. It was found that the neural basis of emotion intensity shifts as emotions unfold over time with emotion explosiveness and accumulation having distinctive neural correlates. © The Author (2017). Published by Oxford University Press.

Morphological Variability and Distinct Protein Profiles of Cultured and Endosymbiotic Symbiodinium cells Isolated from Exaiptasia pulchella

NASA Astrophysics Data System (ADS)

Pasaribu, Buntora; Weng, Li-Chi; Lin, I.-Ping; Camargo, Eddie; Tzen, Jason T. C.; Tsai, Ching-Hsiu; Ho, Shin-Lon; Lin, Mong-Rong; Wang, Li-Hsueh; Chen, Chii-Shiarng; Jiang, Pei-Luen

2015-10-01

Symbiodinium is a dinoflagellate that plays an important role in the physiology of the symbiotic relationships of Cnidarians such as corals and sea anemones. However, it is very difficult to cultivate free-living dinoflagellates after being isolated from the host, as they are very sensitive to environmental changes. How these symbiont cells are supported by the host tissue is still unclear. This study investigated the characteristics of Symbiodinium cells, particularly with respect to the morphological variability and distinct protein profiles of both cultured and endosymbiotic Symbiodinium which were freshly isolated from Exaiptasia pulchella. The response of the cellular morphology of freshly isolated Symbiodinium cells kept under a 12 h L:12 h D cycle to different temperatures was measured. Cellular proliferation was investigated by measuring the growth pattern of Symbiodinium cells, the results of which indicated that the growth was significantly reduced in response to the extreme temperatures. Proteomic analysis of freshly isolated Symbiodinium cells revealed twelve novel proteins that putatively included transcription translation factors, photosystem proteins, and proteins associated with energy and lipid metabolism, as well as defense response. The results of this study will bring more understandings to the mechanisms governing the endosymbiotic relationship between the cnidarians and dinoflagellates.

1H-NMR metabolomic profiling reveals a distinct metabolic recovery response in shoots and roots of temporarily drought-stressed sugar beets

PubMed Central

Maucourt, Mickaël; Deborde, Catherine; Moing, Annick; Gibon, Yves; Goldbach, Heiner E.; Wimmer, Monika A.

2018-01-01

Yield formation in regions with intermittent drought periods depends on the plant’s ability to recover after cessation of the stress. The present work assessed differences in metabolic recovery of leaves and roots of drought-stressed sugar beets with high temporal resolution. Plants were subjected to drought for 13 days, and rewatered for 12 days. At one to two-day intervals, plant material was harvested for untargeted 1H-NMR metabolomic profiling, targeted analyses of hexose-phosphates, starch, amino acids, nitrate and proteins, and physiological measurements including relative water content, osmotic potential, electrolyte leakage and malondialdehyde concentrations. Drought triggered changes in primary metabolism, especially increases in amino acids in both organs, but leaves and roots responded with different dynamics to rewatering. After a transient normalization of most metabolites within 8 days, a second accumulation of amino acids in leaves might indicate a stress imprint beneficial in upcoming drought events. Repair mechanisms seemed important during initial recovery and occurred at the expense of growth for at least 12 days. These results indicate that organ specific metabolic recovery responses might be related to distinct functions and concomitant disparate stress levels in above- and belowground organs. With respect to metabolism, recovery was not simply a reversal of the stress responses. PMID:29738573

The neural basis of emotions varies over time: different regions go with onset- and offset-bound processes underlying emotion intensity

PubMed Central

Verduyn, Philippe; Delaveau, Pauline; Rotgé, Jean-Yves; Kuppens, Peter; Van Mechelen, Iven; Fossati, Philippe

2017-01-01

Abstract According to theories of emotion dynamics, emotions unfold across two phases in which different types of processes come to the fore: emotion onset and emotion offset. Differences in onset-bound processes are reflected by the degree of explosiveness or steepness of the response at onset, and differences in offset-bound processes by the degree of accumulation or intensification of the subsequent response. Whether onset- and offset-bound processes have distinctive neural correlates and, hence, whether the neural basis of emotions varies over time, still remains unknown. In the present fMRI study, we address this question using a recently developed paradigm that allows to disentangle explosiveness and accumulation. Thirty-one participants were exposed to neutral and negative social feedback, and asked to reflect on its contents. Emotional intensity while reading and thinking about the feedback was measured with an intensity profile tracking approach. Using non-negative matrix factorization, the resulting profile data were decomposed in explosiveness and accumulation components, which were subsequently entered as continuous regressors of the BOLD response. It was found that the neural basis of emotion intensity shifts as emotions unfold over time with emotion explosiveness and accumulation having distinctive neural correlates. PMID:28402478

Ultrafast dynamic response of single crystal β-HMX

NASA Astrophysics Data System (ADS)

Zaug, Joseph M.; Armstrong, Michael R.; Crowhurst, Jonathan C.; Radousky, Harry B.; Ferranti, Louis; Swan, Raymond; Gross, Rick; Teslich, Nick E.; Wall, Mark A.; Austin, Ryan A.; Fried, Laurence E.

2017-01-01

We report results from ultrafast compression experiments conducted on β-HMX single crystals. Results consist of nominally 12 picosecond time-resolved wave profile data, (ultrafast time domain interferometry -TDI measurements), that were analyzed to determine high-velocity wave speeds as a function of piston velocity. TDI results are used to validate calculations of anisotropic stress-strain behavior of shocked loaded energetic materials. Our previous results derived using a 350 ps duration compression drive revealed anisotropic elastic wave response in single crystal β-HMX from (110) and (010) impact planes. Here we present results using a 1.05 ns duration compression drive with a 950 ps interferometry window to extend knowledge of the anisotropic dynamic response of β-HMX within eight microns of the initial impact plane. We observe two distinct wave profiles from (010) and three wave profiles from (010) impact planes. The (110) impact plane wave speeds typically exceed (010) impact plane wave speeds at the same piston velocities. The development of multiple hydrodynamic wave profiles begins at 20 GPa for the (110) impact plane and 28 GPa for the (10) impact plane. We compare our ultrafast TDI results with previous gun and plate impact results on β-HMX and PBX9501.

Estimating Between-Person and Within-Person Subscore Reliability with Profile Analysis.

PubMed

Bulut, Okan; Davison, Mark L; Rodriguez, Michael C

2017-01-01

Subscores are of increasing interest in educational and psychological testing due to their diagnostic function for evaluating examinees' strengths and weaknesses within particular domains of knowledge. Previous studies about the utility of subscores have mostly focused on the overall reliability of individual subscores and ignored the fact that subscores should be distinct and have added value over the total score. This study introduces a profile reliability approach that partitions the overall subscore reliability into within-person and between-person subscore reliability. The estimation of between-person reliability and within-person reliability coefficients is demonstrated using subscores from number-correct scoring, unidimensional and multidimensional item response theory scoring, and augmented scoring approaches via a simulation study and a real data study. The effects of various testing conditions, such as subtest length, correlations among subscores, and the number of subtests, are examined. Results indicate that there is a substantial trade-off between within-person and between-person reliability of subscores. Profile reliability coefficients can be useful in determining the extent to which subscores provide distinct and reliable information under various testing conditions.

NICU Network Neurobehavioral Profiles Predict Developmental Outcomes in a Low Risk Sample

PubMed Central

Sucharew, Heidi; Khoury, Jane C.; Xu, Yingying; Succop, Paul; Yolton, Kimberly

2012-01-01

Summary Latent profile analysis (LPA) has been used previously to classify neurobehavioral responses of infants prenatally exposed to cocaine and other drugs of abuse. The objective of this study was to define NICU Network Neurobehavioral Scale (NNNS) profile response patterns in a cohort of infants with no known cocaine exposure or other risks for neurobehavior deficits, and determine whether these profiles predict neurobehavioral outcomes in these low-risk infants. NNNS exams were performed on 355 low-risk infants at approximately 5 weeks after birth. LPA was used to define discrete profiles based on the standard NNNS summary scales. Associations between the infant profiles and neurobehavioral outcomes at one to three years of age were examined. Twelve of the 13 summary scales were used and three discrete NNNS profiles identified: social/easy going infants (44%), hypotonic infants (24%), and high arousal/difficult infants (32%). Statistically significant associations between NNNS profiles and later neurobehavioral outcomes were found for psychomotor development and externalizing behaviors. Hypotonic infants had both lower psychomotor development and lower externalizing scores compared to the other two profiles. In conclusion, three distinct profiles of the NNNS summary scores were identifiable using LPA among infants with no known cocaine exposure. These profile patterns were associated with early childhood neurobehavioral outcome, similar to findings reported in a study of infants with substantial cocaine exposure, demonstrating the utility of this profiling technique in both exposed and unexposed populations. PMID:22686386

Integrative Analysis of Response to Tamoxifen Treatment in ER-Positive Breast Cancer Using GWAS Information and Transcription Profiling.

PubMed

Hicks, Chindo; Kumar, Ranjit; Pannuti, Antonio; Miele, Lucio

2012-01-01

Variable response and resistance to tamoxifen treatment in breast cancer patients remains a major clinical problem. To determine whether genes and biological pathways containing SNPs associated with risk for breast cancer are dysregulated in response to tamoxifen treatment, we performed analysis combining information from 43 genome-wide association studies with gene expression data from 298 ER(+) breast cancer patients treated with tamoxifen and 125 ER(+) controls. We identified 95 genes which distinguished tamoxifen treated patients from controls. Additionally, we identified 54 genes which stratified tamoxifen treated patients into two distinct groups. We identified biological pathways containing SNPs associated with risk for breast cancer, which were dysregulated in response to tamoxifen treatment. Key pathways identified included the apoptosis, P53, NFkB, DNA repair and cell cycle pathways. Combining GWAS with transcription profiling provides a unified approach for associating GWAS findings with response to drug treatment and identification of potential drug targets.

A Molecular Census of Arcuate Hypothalamus and Median Eminence Cell Types

PubMed Central

Campbell, John N.; Macosko, Evan Z.; Fenselau, Henning; Pers, Tune H.; Lyubetskaya, Anna; Tenen, Danielle; Goldman, Melissa; Verstegen, Anne M.J.; Resch, Jon M.; McCarroll, Steven A.; Rosen, Evan D.; Lowell, Bradford B.; Tsai, Linus

2017-01-01

The hypothalamic arcuate-median eminence complex (Arc-ME) controls energy balance, fertility, and growth through molecularly distinct cell types, many of which remain unknown. To catalog cell types in an unbiased way, we profiled gene expression in 20,921 individual cells in and around the adult mouse Arc-ME using Drop-seq. We identify 50 transcriptionally distinct Arc-ME cell populations, including a rare tanycyte population at the Arc-ME diffusion barrier, a novel leptin-sensing neuronal population, multiple AgRP and POMC subtypes, and an orexigenic somatostatin neuronal population. We extended Drop-seq to detect dynamic expression changes across relevant physiological perturbations, revealing cell type-specific responses to energy status, including distinctly responsive subtypes of AgRP and POMC neurons. Finally, integrating our data with human GWAS data implicates two previously unknown neuronal subtypes in the genetic control of obesity. This resource will accelerate biological discovery by providing insights into molecular and cell type diversity from which function can be inferred. PMID:28166221

Who Are Truant Youth? Examining Distinctive Profiles of Truant Youth Using Latent Profile Analysis

ERIC Educational Resources Information Center

Maynard, Brandy R.; Salas-Wright, Christopher P.; Vaughn, Michael G.; Peters, Kristen E.

2012-01-01

The present study explored the heterogeneity of truant youth to provide a more nuanced examination of the nature of adolescent truancy and examine distinct profiles of truant youth as they relate to externalizing behaviors. Latent profile analysis was employed to examine the heterogeneity of truant youth by using a nationally representative sample…

Psychosocial Outcomes 3 to 10 Years After Donation in the Adult to Adult Living Donor Liver Transplantation Cohort Study (A2ALL)

PubMed Central

Dew, Mary Amanda; DiMartini, Andrea F.; Ladner, Daniela P.; Simpson, Mary Ann; Pomfret, Elizabeth A.; Gillespie, Brenda W.; Merion, Robert M.; Zee, Jarcy; Smith, Abigail R.; Holtzman, Susan; Sherker, Averell H.; Weinrieb, Robert; Fisher, Robert A.; Emond, Jean C.; Freise, Chris E.; Burton, James R.; Butt, Zeeshan

2016-01-01

Background Studies of liver donors’ psychosocial outcomes focus on the short-term and rely largely on quality-of-life measures not specific to donation. We sought to examine long-term donation effects on three psychosocial domains: perceived physical, emotional, and socioeconomic outcomes. Methods Individuals donating 3–10 years previously at nine centers were eligible for telephone surveys. Survey responses were examined descriptively. Cluster analysis was used to identify distinct donor groups based on response profiles across psychosocial domains. Potential predictors of response profiles were evaluated with regression analysis. Results 517 donors (66%) participated (M=5.8 years postdonation, SD=1.9). 15%–48% of donors endorsed current donation-related physical health problems and concerns, and 7%–60% reported socioeconomic concerns (e.g., insurance difficulties, financial expenditures). However, on average, donors experienced high psychological growth, and 90% felt positively about donation. Cluster analysis revealed five donor groups. One group showed high psychological benefit, with little endorsement of physical or socioeconomic concerns (15% of donors). Four groups showed less favorable profiles, with varying combinations of difficulties. The largest such group showed high endorsement of physical concerns and financial expenditures, and only modest psychological benefit (31% of donors). Men and non-Hispanic whites were most likely to have unfavorable response profiles (p<.01). Compared with donors aged 19–30, older donors were less likely to have unfavorable profiles; these differences were significant for donors aged >40–50 (p’s<.008). Conclusions Even many years postdonation, donors report adverse physical and socioeconomic effects, but positive emotional effects as well. Identification of response profiles and predictors may improve targeting of postdonation surveillance and care. PMID:27152918

Profiles of influenza A/H1N1 vaccine response using hemagglutination-inhibition titers.

PubMed

Jacobson, Robert M; Grill, Diane E; Oberg, Ann L; Tosh, Pritish K; Ovsyannikova, Inna G; Poland, Gregory A

2015-01-01

To identify distinct antibody profiles among adults 50-to-74 years old using influenza A/H1N1 HI titers up to 75 days after vaccination. Healthy subjects 50 to 74 years old received the 2010-2011 trivalent inactivated influenza vaccine. We measured venous samples from Days 0, 28, and 75 for HI and VNA and B-cell ELISPOTs. Of 106 subjects, HI titers demonstrated a ceiling effect for 11 or 10% for those with a pre-vaccination HI titer of 1:640 where no subject post-vaccination had an increase in titer. Of the remaining 95 subjects, only 37 or 35% overall had at least a 4-fold increase by Day 28. Of these 37, 3 waned at least 4-fold, and 13 others 2-fold. Thus 15% of the subjects showed waning antibody titers by Day 75. More than half failed to respond at all. The profiles populated by these subjects as defined by HI did not vary with age or gender. The VNA results mimicked the HI profiles, but the profiles for B-cell ELISPOT did not. HI titers at Days 0, 28, and 75 populate 4 biologically plausible profiles. Limitations include lack of consensus for operationally defining waning as well as for the apparent ceiling. Furthermore, though well accepted as a marker for vaccine response, assigning thresholds with HI has limitations. However, VNA closely matches HI in populating these profiles. Thus, we hold that these profiles, having face- and content-validity, may provide a basis for understanding variation in genomic and transcriptomic response to influenza vaccination in this age group.

Utilization of ACL Injury Biomechanical and Neuromuscular Risk Profile Analysis to Determine the Effectiveness of Neuromuscular Training.

PubMed

Hewett, Timothy E; Ford, Kevin R; Xu, Yingying Y; Khoury, Jane; Myer, Gregory D

2016-12-01

The widespread use of anterior cruciate ligament (ACL) injury prevention interventions has not been effective in reducing the injury incidence among female athletes who participate in high-risk sports. The purpose of this study was to determine if biomechanical and neuromuscular factors that contribute to the knee abduction moment (KAM), a predictor of future ACL injuries, could be used to characterize athletes by a distinct factor. Specifically, we hypothesized that a priori selected biomechanical and neuromuscular factors would characterize participants into distinct at-risk profiles. Controlled laboratory study. A total of 624 female athletes who participated in jumping, cutting, and pivoting sports underwent testing before their competitive season. During testing, athletes performed drop-jump tasks from which biomechanical measures were captured. Using data from these tasks, latent profile analysis (LPA) was conducted to identify distinct profiles based on preintervention biomechanical and neuromuscular measures. As a validation, we examined whether the profile membership was a significant predictor of the KAM. LPA using 6 preintervention biomechanical measures selected a priori resulted in 3 distinct profiles, including a low (profile 1), moderate (profile 2), and high (profile 3) risk for ACL injuries. Athletes with profiles 2 and 3 had a significantly higher KAM compared with those with profile 1 (P < .05). This is the first study to use LPA of biomechanical landing data to create ACL injury risk profiles. Three distinct risk groups were identified based on differences in the peak KAM. These findings demonstrate the existence of discernable groups of athletes that may benefit from injury prevention interventions. ClinicalTrials.gov NCT identifier: NCT01034527. © 2016 The Author(s).

Profile-likelihood Confidence Intervals in Item Response Theory Models.

PubMed

Chalmers, R Philip; Pek, Jolynn; Liu, Yang

2017-01-01

Confidence intervals (CIs) are fundamental inferential devices which quantify the sampling variability of parameter estimates. In item response theory, CIs have been primarily obtained from large-sample Wald-type approaches based on standard error estimates, derived from the observed or expected information matrix, after parameters have been estimated via maximum likelihood. An alternative approach to constructing CIs is to quantify sampling variability directly from the likelihood function with a technique known as profile-likelihood confidence intervals (PL CIs). In this article, we introduce PL CIs for item response theory models, compare PL CIs to classical large-sample Wald-type CIs, and demonstrate important distinctions among these CIs. CIs are then constructed for parameters directly estimated in the specified model and for transformed parameters which are often obtained post-estimation. Monte Carlo simulation results suggest that PL CIs perform consistently better than Wald-type CIs for both non-transformed and transformed parameters.

Process signatures in glatiramer acetate synthesis: structural and functional relationships.

PubMed

Campos-García, Víctor R; Herrera-Fernández, Daniel; Espinosa-de la Garza, Carlos E; González, German; Vallejo-Castillo, Luis; Avila, Sandra; Muñoz-García, Leslie; Medina-Rivero, Emilio; Pérez, Néstor O; Gracia-Mora, Isabel; Pérez-Tapia, Sonia Mayra; Salazar-Ceballos, Rodolfo; Pavón, Lenin; Flores-Ortiz, Luis F

2017-09-21

Glatiramer Acetate (GA) is an immunomodulatory medicine approved for the treatment of multiple sclerosis, whose mechanisms of action are yet to be fully elucidated. GA is comprised of a complex mixture of polypeptides with different amino acid sequences and structures. The lack of sensible information about physicochemical characteristics of GA has contributed to its comprehensiveness complexity. Consequently, an unambiguous determination of distinctive attributes that define GA is of highest relevance towards dissecting its identity. Herein we conducted a study of characteristic GA heterogeneities throughout its manufacturing process (process signatures), revealing a strong impact of critical process parameters (CPPs) on the reactivity of amino acid precursors; reaction initiation and polymerization velocities; and peptide solubility, susceptibility to hydrolysis, and size-exclusion properties. Further, distinctive GA heterogeneities were correlated to defined immunological and toxicological profiles, revealing that GA possesses a unique repertoire of active constituents (epitopes) responsible of its immunological responses, whose modification lead to altered profiles. This novel approach established CPPs influence on intact GA peptide mixture, whose physicochemical identity cannot longer rely on reduced properties (based on complete or partial GA degradation), providing advanced knowledge on GA structural and functional relationships to ensure a consistent manufacturing of safe and effective products.

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

Behçet's: A Disease or a Syndrome? Answer from an Expression Profiling Study

PubMed Central

Oğuz, Ali Kemal; Yılmaz, Seda Taşır; Oygür, Çağdaş Şahap; Çandar, Tuba; Sayın, Irmak; Kılıçoğlu, Sibel Serin; Ergün, İhsan; Ateş, Aşkın; Özdağ, Hilal; Akar, Nejat

2016-01-01

Behçet’s disease (BD) is a chronic, relapsing, multisystemic inflammatory disorder with unanswered questions regarding its etiology/pathogenesis and classification. Distinct manifestation based subsets, pronounced geographical variations in expression, and discrepant immunological abnormalities raised the question whether Behçet’s is “a disease or a syndrome”. To answer the preceding question we aimed to display and compare the molecular mechanisms underlying distinct subsets of BD. For this purpose, the expression data of the gene expression profiling and association study on BD by Xavier et al (2013) was retrieved from GEO database and reanalysed by gene expression data analysis/visualization and bioinformatics enrichment tools. There were 15 BD patients (B) and 14 controls (C). Three subsets of BD patients were generated: MB (isolated mucocutaneous manifestations, n = 7), OB (ocular involvement, n = 4), and VB (large vein thrombosis, n = 4). Class comparison analyses yielded the following numbers of differentially expressed genes (DEGs); B vs C: 4, MB vs C: 5, OB vs C: 151, VB vs C: 274, MB vs OB: 215, MB vs VB: 760, OB vs VB: 984. Venn diagram analysis showed that there were no common DEGs in the intersection “MB vs C” ∩ “OB vs C” ∩ “VB vs C”. Cluster analyses successfully clustered distinct expressions of BD. During gene ontology term enrichment analyses, categories with relevance to IL-8 production (MB vs C) and immune response to microorganisms (OB vs C) were differentially enriched. Distinct subsets of BD display distinct expression profiles and different disease associated pathways. Based on these clear discrepancies, the designation as “Behçet’s syndrome” (BS) should be encouraged and future research should take into consideration the immunogenetic heterogeneity of BS subsets. Four gene groups, namely, negative regulators of inflammation (CD69, CLEC12A, CLEC12B, TNFAIP3), neutrophil granule proteins (LTF, OLFM4, AZU1, MMP8, DEFA4, CAMP), antigen processing and presentation proteins (CTSS, ERAP1), and regulators of immune response (LGALS2, BCL10, ITCH, CEACAM8, CD36, IL8, CCL4, EREG, NFKBIZ, CCR2, CD180, KLRC4, NFAT5) appear to be instrumental in BS immunopathogenesis. PMID:26890122

Kinetic insulation as an effective mechanism for achieving pathway specificity in intracellular signaling networks

PubMed Central

Behar, Marcelo; Dohlman, Henrik G.; Elston, Timothy C.

2007-01-01

Intracellular signaling pathways that share common components often elicit distinct physiological responses. In most cases, the biochemical mechanisms responsible for this signal specificity remain poorly understood. Protein scaffolds and cross-inhibition have been proposed as strategies to prevent unwanted cross-talk. Here, we report a mechanism for signal specificity termed “kinetic insulation.” In this approach signals are selectively transmitted through the appropriate pathway based on their temporal profile. In particular, we demonstrate how pathway architectures downstream of a common component can be designed to efficiently separate transient signals from signals that increase slowly over time. Furthermore, we demonstrate that upstream signaling proteins can generate the appropriate input to the common pathway component regardless of the temporal profile of the external stimulus. Our results suggest that multilevel signaling cascades may have evolved to modulate the temporal profile of pathway activity so that stimulus information can be efficiently encoded and transmitted while ensuring signal specificity. PMID:17913886

Dissociable Roles of Right Inferior Frontal Cortex and Anterior Insula in Inhibitory Control: Evidence from Intrinsic and Task-Related Functional Parcellation, Connectivity, and Response Profile Analyses across Multiple Datasets

PubMed Central

Ryali, Srikanth; Chen, Tianwen; Li, Chiang-Shan R.

2014-01-01

The right inferior frontal cortex (rIFC) and the right anterior insula (rAI) have been implicated consistently in inhibitory control, but their differential roles are poorly understood. Here we use multiple quantitative techniques to dissociate the functional organization and roles of the rAI and rIFC. We first conducted a meta-analysis of 70 published inhibitory control studies to generate a commonly activated right fronto-opercular cortex volume of interest (VOI). We then segmented this VOI using two types of features: (1) intrinsic brain activity; and (2) stop-signal task-evoked hemodynamic response profiles. In both cases, segmentation algorithms identified two stable and distinct clusters encompassing the rAI and rIFC. The rAI and rIFC clusters exhibited several distinct functional characteristics. First, the rAI showed stronger intrinsic and task-evoked functional connectivity with the anterior cingulate cortex, whereas the rIFC had stronger intrinsic and task-evoked functional connectivity with dorsomedial prefrontal and lateral fronto-parietal cortices. Second, the rAI showed greater activation than the rIFC during Unsuccessful, but not Successful, Stop trials, and multivoxel response profiles in the rAI, but not the rIFC, accurately differentiated between Successful and Unsuccessful Stop trials. Third, activation in the rIFC, but not rAI, predicted individual differences in inhibitory control abilities. Crucially, these findings were replicated in two independent cohorts of human participants. Together, our findings provide novel quantitative evidence for the dissociable roles of the rAI and rIFC in inhibitory control. We suggest that the rAI is particularly important for detecting behaviorally salient events, whereas the rIFC is more involved in implementing inhibitory control. PMID:25355218

4-dimensional functional profiling in the convulsant-treated larval zebrafish brain.

PubMed

Winter, Matthew J; Windell, Dylan; Metz, Jeremy; Matthews, Peter; Pinion, Joe; Brown, Jonathan T; Hetheridge, Malcolm J; Ball, Jonathan S; Owen, Stewart F; Redfern, Will S; Moger, Julian; Randall, Andrew D; Tyler, Charles R

2017-07-26

Functional neuroimaging, using genetically-encoded Ca 2+ sensors in larval zebrafish, offers a powerful combination of high spatiotemporal resolution and higher vertebrate relevance for quantitative neuropharmacological profiling. Here we use zebrafish larvae with pan-neuronal expression of GCaMP6s, combined with light sheet microscopy and a novel image processing pipeline, for the 4D profiling of chemoconvulsant action in multiple brain regions. In untreated larvae, regions associated with autonomic functionality, sensory processing and stress-responsiveness, consistently exhibited elevated spontaneous activity. The application of drugs targeting different convulsant mechanisms (4-Aminopyridine, Pentylenetetrazole, Pilocarpine and Strychnine) resulted in distinct spatiotemporal patterns of activity. These activity patterns showed some interesting parallels with what is known of the distribution of their respective molecular targets, but crucially also revealed system-wide neural circuit responses to stimulation or suppression. Drug concentration-response curves of neural activity were identified in a number of anatomically-defined zebrafish brain regions, and in vivo larval electrophysiology, also conducted in 4dpf larvae, provided additional measures of neural activity. Our quantification of network-wide chemoconvulsant drug activity in the whole zebrafish brain illustrates the power of this approach for neuropharmacological profiling in applications ranging from accelerating studies of drug safety and efficacy, to identifying pharmacologically-altered networks in zebrafish models of human neurological disorders.

Serological & molecular diagnostic surveys combined with examining hematological profiles suggest increased levels of infection & hematological response of cattle to babesiosis infections compared to native buffaloes in Egypt

USDA-ARS?s Scientific Manuscript database

Background: Babesiosis threatens the development of the cattle and buffaloes industries in Egypt and improved control is needed. The main objectives of this study are surveying the presence of bovine babesiosis in distinct selected bovine and buffalo populations in Egypt using novel molecular and pr...

Distinct Gene Expression Profiles in Peripheral Blood Mononuclear Cells from Patients Infected with Vaccinia Virus, Yellow Fever 17D Virus, or Upper Respiratory Infections Running Title: PBMC Expression Response to Viral Agents

PubMed Central

Scherer, Christina A.; Magness, Charles L.; Steiger, Kathryn V.; Poitinger, Nicholas D.; Caputo, Christine M.; Miner, Douglas G.; Winokur, Patricia L.; Klinzman, Donna; McKee, Janice; Pilar, Christine; Ward, Patricia A.; Gillham, Martha H.; Haulman, N. Jean; Stapleton, Jack T.; Iadonato, Shawn P.

2007-01-01

Gene expression in human peripheral blood mononuclear cells was systematically evaluated following smallpox and yellow fever vaccination, and naturally occurring upper respiratory infection (URI). All three infections were characterized by the induction of many interferon stimulated genes, as well as enhanced expression of genes involved in proteolysis and antigen presentation. Vaccinia infection was also characterized by a distinct expression signature composed of up-regulation of monocyte response genes, with repression of genes expressed by B and T-cells. In contrast, the yellow fever host response was characterized by a suppression of ribosomal and translation factors, distinguishing this infection from vaccinia and URI. No significant URI-specific signature was observed, perhaps reflecting greater heterogeneity in the study population and etiological agents. Taken together, these data suggest that specific host gene expression signatures may be identified that distinguish one or a small number of virus agents. PMID:17651872

Comparative expression analysis reveals lineage relationships between human and murine gliomas and a dominance of glial signatures during tumor propagation in vitro.

PubMed

Henriquez, Nico V; Forshew, Tim; Tatevossian, Ruth; Ellis, Matthew; Richard-Loendt, Angela; Rogers, Hazel; Jacques, Thomas S; Reitboeck, Pablo Garcia; Pearce, Kerra; Sheer, Denise; Grundy, Richard G; Brandner, Sebastian

2013-09-15

Brain tumors are thought to originate from stem/progenitor cell populations that acquire specific genetic mutations. Although current preclinical models have relevance to human pathogenesis, most do not recapitulate the histogenesis of the human disease. Recently, a large series of human gliomas and medulloblastomas were analyzed for genetic signatures of prognosis and therapeutic response. Using a mouse model system that generates three distinct types of intrinsic brain tumors, we correlated RNA and protein expression levels with human brain tumors. A combination of genetic mutations and cellular environment during tumor propagation defined the incidence and phenotype of intrinsic murine tumors. Importantly, in vitro passage of cancer stem cells uniformly promoted a glial expression profile in culture and in brain tumors. Gene expression profiling revealed that experimental gliomas corresponded to distinct subclasses of human glioblastoma, whereas experimental supratentorial primitive neuroectodermal tumors (sPNET) correspond to atypical teratoid/rhabdoid tumor (AT/RT), a rare childhood tumor. ©2013 AACR.

Profiling human breast epithelial cells using single cell RNA sequencing identifies cell diversity.

PubMed

Nguyen, Quy H; Pervolarakis, Nicholas; Blake, Kerrigan; Ma, Dennis; Davis, Ryan Tevia; James, Nathan; Phung, Anh T; Willey, Elizabeth; Kumar, Raj; Jabart, Eric; Driver, Ian; Rock, Jason; Goga, Andrei; Khan, Seema A; Lawson, Devon A; Werb, Zena; Kessenbrock, Kai

2018-05-23

Breast cancer arises from breast epithelial cells that acquire genetic alterations leading to subsequent loss of tissue homeostasis. Several distinct epithelial subpopulations have been proposed, but complete understanding of the spectrum of heterogeneity and differentiation hierarchy in the human breast remains elusive. Here, we use single-cell mRNA sequencing (scRNAseq) to profile the transcriptomes of 25,790 primary human breast epithelial cells isolated from reduction mammoplasties of seven individuals. Unbiased clustering analysis reveals the existence of three distinct epithelial cell populations, one basal and two luminal cell types, which we identify as secretory L1- and hormone-responsive L2-type cells. Pseudotemporal reconstruction of differentiation trajectories produces one continuous lineage hierarchy that closely connects the basal lineage to the two differentiated luminal branches. Our comprehensive cell atlas provides insights into the cellular blueprint of the human breast epithelium and will form the foundation to understand how the system goes awry during breast cancer.

Individual Distinctive Features of Self-Regulation Processes Peculiar to Students of Different Profiles of Lateral Organization

ERIC Educational Resources Information Center

Korneeva, Svetlana A.; Zherebnenko, Oksana A.; Mukhamedzyanova, Flera G.; Moskalenko, Svetlana V.; Gorelikova, Olga N.

2016-01-01

The research paper presents an analysis of the interrelation between the lateral organisation profiles' indicators and self-regulation features. The existence of significant distinctions in the processes of self-regulation among respondents with different variants of lateral profiles of the interhemispheric asymmetry is proved, as well as the…

Inter-individual variability and genetic influences on cytokine responses against bacterial and fungal pathogens

PubMed Central

Li, Yang; Oosting, Marije; Deelen, Patrick; Ricaño-Ponce, Isis; Smeekens, Sanne; Jaeger, Martin; Matzaraki, Vasiliki; Swertz, Morris A.; Xavier, Ramnik J.; Franke, Lude; Wijmenga, Cisca; Joosten, Leo A.B.; Kumar, Vinod; Netea, Mihai G.

2016-01-01

Little is known about the inter-individual variation of cytokine responses to different pathogens in healthy individuals. To systematically describe cytokine responses elicited by distinct pathogens, and to determine the impact of genetic variation on cytokine production, we profiled cytokines produced by peripheral blood mononuclear cells from 197 individuals of European origin from the 200 Functional Genomics (200FG) cohort within the Human Functional Genomics Study (www.humanfunctionalgenomics.org), obtained over three different years. By comparing bacteria- and fungi-induced cytokine profiles, we show that most cytokine responses are organized around a physiological response to specific pathogens, rather than around a particular immune pathway or cytokine. We then correlated genome-wide SNP genotypes with cytokine abundance and identified six cytokine QTLs. Among them, a cytokine QTL at NAA35-GOLM1 locus markedly modulates IL-6 production in response to multiple pathogens, and associated with susceptibility to candidemia. Furthermore, the cytokine QTLs we identified are enriched among SNPs previously associated with infectious diseases and heart diseases. These data reveal and begin to explain the variability in cytokine production by human immune cells in response to pathogens. PMID:27376574

Transcriptional profiling of Haemophilus parasuis SH0165 response to tilmicosin.

PubMed

Liu, Yingyu; Chen, Pin; Wang, Yang; Li, Wentao; Cheng, Shuang; Wang, Chunmei; Zhang, Anding; He, Qigai

2012-12-01

The Haemophilus parasuis respiratory tract pathogen poses a severe threat to the swine industry despite available antimicrobial therapies. To gain a more detailed understanding of the molecular mechanisms underlying H. parasuis response to tilmicosin treatment, microarray technology was applied to analyze the variation in gene expression of isolated H. parasuis SH0165 treated in vitro with subinhibitory (0.25 μg/ml) and inhibitory (8 μg/ml) concentrations. Tilmicosin treatment induced differential expression of 405 genes, the encoded products of which are mainly involved in the heat shock response, protein synthesis, and intracellular transportation. The subinhibitory and inhibitory concentrations of tilmicosin induced distinctive gene expression profiles of shared and unique changes, respectively. These changes included 302 genes mainly involved in protein export and the phosphotransferase system to sustain cell growth, and 198 genes mainly related to RNA polymerase, recombination, and repair to inhibit cell growth. In silico analysis of functions related to the differentially expressed genes suggested that adaptation of H. parasuis SH0165 to tilmicosin involves modulation of protein synthesis and membrane transport. Collectively, the genes comprising each transcriptional profile of H. parasuis response to tilmicosin provide novel insights into the physiological functions of this economically significant bacterium and may represent targets of future molecular therapeutic strategies.

Comparative metagenomic and metatranscriptomic analyses of microbial communities in acid mine drainage.

PubMed

Chen, Lin-xing; Hu, Min; Huang, Li-nan; Hua, Zheng-shuang; Kuang, Jia-liang; Li, Sheng-jin; Shu, Wen-sheng

2015-07-01

The microbial communities in acid mine drainage have been extensively studied to reveal their roles in acid generation and adaption to this environment. Lacking, however, are integrated community- and organism-wide comparative gene transcriptional analyses that could reveal the response and adaptation mechanisms of these extraordinary microorganisms to different environmental conditions. In this study, comparative metagenomics and metatranscriptomics were performed on microbial assemblages collected from four geochemically distinct acid mine drainage (AMD) sites. Taxonomic analysis uncovered unexpectedly high microbial biodiversity of these extremely acidophilic communities, and the abundant taxa of Acidithiobacillus, Leptospirillum and Acidiphilium exhibited high transcriptional activities. Community-wide comparative analyses clearly showed that the AMD microorganisms adapted to the different environmental conditions via regulating the expression of genes involved in multiple in situ functional activities, including low-pH adaptation, carbon, nitrogen and phosphate assimilation, energy generation, environmental stress resistance, and other functions. Organism-wide comparative analyses of the active taxa revealed environment-dependent gene transcriptional profiles, especially the distinct strategies used by Acidithiobacillus ferrivorans and Leptospirillum ferrodiazotrophum in nutrients assimilation and energy generation for survival under different conditions. Overall, these findings demonstrate that the gene transcriptional profiles of AMD microorganisms are closely related to the site physiochemical characteristics, providing clues into the microbial response and adaptation mechanisms in the oligotrophic, extremely acidic environments.

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.

Proteome and metabolome profiling of cytokinin action in Arabidopsis identifying both distinct and similar responses to cytokinin down- and up-regulation.

PubMed

Černý, Martin; Kuklová, Alena; Hoehenwarter, Wolfgang; Fragner, Lena; Novák, Ondrej; Rotková, Gabriela; Jedelsky, Petr L; Žáková, Katerina; Šmehilová, Mária; Strnad, Miroslav; Weckwerth, Wolfram; Brzobohaty, Bretislav

2013-11-01

In plants, numerous developmental processes are controlled by cytokinin (CK) levels and their ratios to levels of other hormones. While molecular mechanisms underlying the regulatory roles of CKs have been intensely researched, proteomic and metabolomic responses to CK deficiency are unknown. Transgenic Arabidopsis seedlings carrying inducible barley cytokinin oxidase/dehydrogenase (CaMV35S>GR>HvCKX2) and agrobacterial isopentenyl transferase (CaMV35S>GR>ipt) constructs were profiled to elucidate proteome- and metabolome-wide responses to down- and up-regulation of CK levels, respectively. Proteome profiling identified >1100 proteins, 155 of which responded to HvCKX2 and/or ipt activation, mostly involved in growth, development, and/or hormone and light signalling. The metabolome profiling covered 79 metabolites, 33 of which responded to HvCKX2 and/or ipt activation, mostly amino acids, carbohydrates, and organic acids. Comparison of the data sets obtained from activated CaMV35S>GR>HvCKX2 and CaMV35S>GR>ipt plants revealed unexpectedly extensive overlaps. Integration of the proteomic and metabolomic data sets revealed: (i) novel components of molecular circuits involved in CK action (e.g. ribosomal proteins); (ii) previously unrecognized links to redox regulation and stress hormone signalling networks; and (iii) CK content markers. The striking overlaps in profiles observed in CK-deficient and CK-overproducing seedlings might explain surprising previously reported similarities between plants with down- and up-regulated CK levels.

A pharmacological profile of the aldehyde receptor repertoire in rat olfactory epithelium

PubMed Central

Araneda, Ricardo C; Peterlin, Zita; Zhang, Xinmin; Chesler, Alex; Firestein, Stuart

2004-01-01

Several lines of evidence suggest that odorants are recognized through a combinatorial process in the olfactory system; a single odorant is recognized by multiple receptors and multiple odorants are recognized by the same receptor. However few details of how this might actually function for any particular odour set or receptor family are available. Approaching the problem from the ligands rather than the receptors, we used the response to a common odorant, octanal, as the basis for defining multiple receptor profiles. Octanal and other aldehydes induce large EOG responses in the rodent olfactory epithelium, suggesting that these compounds activate a large number of odour receptors (ORs). Here, we have determined and compared the pharmacological profile of different octanal receptors using Ca2+ imaging in isolated olfactory sensory neurones (OSNs). It is believed that each OSN expresses only one receptor, thus the response profile of each cell corresponds to the pharmacological profile of one particular receptor. We stimulated the cells with a panel of nine odorants, which included octanal, octanoic acid, octanol and cinnamaldehyde among others (all at 30μm). Cluster analysis revealed several distinct pharmacological profiles for cells that were all sensitive to octanal. Some receptors had a broad molecular range, while others were activated only by octanal. Comparison of the profiles with that of the one identified octanal receptor, OR-I7, indicated several differences. While OR-I7 is activated by low concentrations of octanal and blocked by citral, other receptors were less sensitive to octanal and not blocked by citral. A lower estimate for the maximal number of octanal receptors is between 33 and 55. This large number of receptors for octanal suggests that, although the peripheral olfactory system is endowed with high sensitivity, discrimination among different compounds probably requires further central processing. PMID:14724183

Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers.

PubMed

Bloom, Chloe I; Graham, Christine M; Berry, Matthew P R; Rozakeas, Fotini; Redford, Paul S; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A; Wilkinson, Robert J; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Valeyre, Dominique; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-Pei; Lipman, Marc; O'Garra, Anne

2013-01-01

New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.

Thriving on Pressure: A Factor Mixture Analysis of Sport Performers' Responses to Competitive Encounters.

PubMed

Brown, Daniel J; Arnold, Rachel; Standage, Martyn; Fletcher, David

2017-12-01

Although considerable research exists on performers' responses to sporting encounters, little is known about thriving in sport contexts. The current study examined if distinct response patterns existed between sport performers who thrived in competitive encounters compared with those who did not. Participants were 535 sport performers (134 women; M age  = 23.60 years, SD age  = 8.08; M competing  = 11.84 years, SD competing  = 7.11). Results of factor mixture analysis supported a four-profile solution comprising a thriving group (n = 146), a low-functioning group (n = 38), and two groups characterized by scores marginally above (n = 131) and below (n = 209) the sample mean. Profile membership was found to be predicted by personal enablers (viz., personal resilient qualities, psychological skills use) and process variables (viz., basic psychological need satisfaction and frustration, challenge appraisal). This examination of thriving in sport performers offers significant implications for research and practice.

Protective immune responses against West Nile virus are primed by distinct complement activation pathways.

PubMed

Mehlhop, Erin; Diamond, Michael S

2006-05-15

West Nile virus (WNV) causes a severe infection of the central nervous system in several vertebrate animals including humans. Prior studies have shown that complement plays a critical role in controlling WNV infection in complement (C) 3(-/-) and complement receptor 1/2(-/-) mice. Here, we dissect the contributions of the individual complement activation pathways to the protection from WNV disease. Genetic deficiencies in C1q, C4, factor B, or factor D all resulted in increased mortality in mice, suggesting that all activation pathways function together to limit WNV spread. In the absence of alternative pathway complement activation, WNV disseminated into the central nervous system at earlier times and was associated with reduced CD8+ T cell responses yet near normal anti-WNV antibody profiles. Animals lacking the classical and lectin pathways had deficits in both B and T cell responses to WNV. Finally, and somewhat surprisingly, C1q was required for productive infection in the spleen but not for development of adaptive immune responses after WNV infection. Our results suggest that individual pathways of complement activation control WNV infection by priming adaptive immune responses through distinct mechanisms.

Mindfulness and Psychological Health Outcomes: A Latent Profile Analysis among Military Personnel and College Students.

PubMed

Bravo, Adrian J; Pearson, Matthew R; Kelley, Michelle L

2018-02-01

Previous research on trait mindfulness facets using person-centered analyses (e.g., latent profile analysis [LPA]) has identified four distinct mindfulness profiles among college students: a high mindfulness group (high on all facets of the Five-Factor Mindfulness Questionnaire [FFMQ]), a judgmentally observing group (highest on observing, but low on non-judging of inner experience and acting with awareness), a non-judgmentally aware group (high on non-judging of inner experience and acting with awareness, but very low on observing), and a low mindfulness group (low on all facets of the FFMQ). In the present study, we used LPA to identify distinct mindfulness profiles in a community based sample of U.S. military personnel (majority veterans; n = 407) and non-military college students ( n = 310) and compare these profiles on symptoms of psychological health outcomes (e.g., suicidality, PTSD, anxiety, rumination) and percentage of participants exceeding clinically significant cut-offs for depressive symptoms, substance use, and alcohol use. In the subsample of college students, we replicated previous research and found four distinct mindfulness profiles; however, in the military subsample we found three distinct mindfulness profiles (a combined low mindfulness/judgmentally observing class). In both subsamples, we found that the most adaptive profile was the "high mindfulness" profile (i.e., demonstrated the lowest scores on all psychological symptoms and the lowest probability of exceeding clinical cut-offs). Based on these findings, we purport that the comprehensive examination of an individual's mindfulness profile could help clinicians tailor interventions/treatments that capitalize on individual's specific strengths and work to address their specific deficits.

Indications for distinct pathogenic mechanisms of asbestos and silica through gene expression profiling of the response of lung epithelial cells

PubMed Central

Perkins, Timothy N.; Peeters, Paul M.; Shukla, Arti; Arijs, Ingrid; Dragon, Julie; Wouters, Emiel F.M.; Reynaert, Niki L.; Mossman, Brooke T.

2015-01-01

Occupational and environmental exposures to airborne asbestos and silica are associated with the development of lung fibrosis in the forms of asbestosis and silicosis, respectively. However, both diseases display distinct pathologic presentations, likely associated with differences in gene expression induced by different mineral structures, composition and bio-persistent properties. We hypothesized that effects of mineral exposure in the airway epithelium may dictate deviating molecular events that may explain the different pathologies of asbestosis versus silicosis. Using robust gene expression-profiling in conjunction with in-depth pathway analysis, we assessed early (24 h) alterations in gene expression associated with crocidolite asbestos or cristobalite silica exposures in primary human bronchial epithelial cells (NHBEs). Observations were confirmed in an immortalized line (BEAS-2B) by QRT-PCR and protein assays. Utilization of overall gene expression, unsupervised hierarchical cluster analysis and integrated pathway analysis revealed gene alterations that were common to both minerals or unique to either mineral. Our findings reveal that both minerals had potent effects on genes governing cell adhesion/migration, inflammation, and cellular stress, key features of fibrosis. Asbestos exposure was most specifically associated with aberrant cell proliferation and carcinogenesis, whereas silica exposure was highly associated with additional inflammatory responses, as well as pattern recognition, and fibrogenesis. These findings illustrate the use of gene-profiling as a means to determine early molecular events that may dictate pathological processes induced by exogenous cellular insults. In addition, it is a useful approach for predicting the pathogenicity of potentially harmful materials. PMID:25351596

Ethnic Variation in Inflammatory Profile in Tuberculosis

PubMed Central

Coussens, Anna K.; Wilkinson, Robert J.; Nikolayevskyy, Vladyslav; Elkington, Paul T.; Hanifa, Yasmeen; Islam, Kamrul; Timms, Peter M.; Bothamley, Graham H.; Claxton, Alleyna P.; Packe, Geoffrey E.; Darmalingam, Mathina; Davidson, Robert N.; Milburn, Heather J.; Baker, Lucy V.; Barker, Richard D.; Drobniewski, Francis A.; Mein, Charles A.; Bhaw-Rosun, Leena; Nuamah, Rosamond A.; Griffiths, Christopher J.; Martineau, Adrian R.

2013-01-01

Distinct phylogenetic lineages of Mycobacterium tuberculosis (MTB) cause disease in patients of particular genetic ancestry, and elicit different patterns of cytokine and chemokine secretion when cultured with human macrophages in vitro. Circulating and antigen-stimulated concentrations of these inflammatory mediators might therefore be expected to vary significantly between tuberculosis patients of different ethnic origin. Studies to characterise such variation, and to determine whether it relates to host or bacillary factors, have not been conducted. We therefore compared circulating and antigen-stimulated concentrations of 43 inflammatory mediators and 14 haematological parameters (inflammatory profile) in 45 pulmonary tuberculosis patients of African ancestry vs. 83 patients of Eurasian ancestry in London, UK, and investigated the influence of bacillary and host genotype on these profiles. Despite having similar demographic and clinical characteristics, patients of differing ancestry exhibited distinct inflammatory profiles at presentation: those of African ancestry had lower neutrophil counts, lower serum concentrations of CCL2, CCL11 and vitamin D binding protein (DBP) but higher serum CCL5 concentrations and higher antigen-stimulated IL-1 receptor antagonist and IL-12 secretion. These differences associated with ethnic variation in host DBP genotype, but not with ethnic variation in MTB strain. Ethnic differences in inflammatory profile became more marked following initiation of antimicrobial therapy, and immunological correlates of speed of elimination of MTB from the sputum differed between patients of African vs. Eurasian ancestry. Our study demonstrates a hitherto unappreciated degree of ethnic heterogeneity in inflammatory profile in tuberculosis patients that associates primarily with ethnic variation in host, rather than bacillary, genotype. Candidate immunodiagnostics and immunological biomarkers of response to antimicrobial therapy should be derived and validated in tuberculosis patients of different ethnic origin. PMID:23853590

Dose-response relationships in gene expression profiles in rainbow trout, Oncorhyncus mykiss, exposed to ethynylestradiol.

PubMed

Hook, Sharon E; Skillman, Ann D; Small, Jack A; Schultz, Irvin R

2006-07-01

Determining how gene expression profiles change with toxicant dose will improve the utility of arrays in identifying biomarkers and modes of toxic action. Isogenic rainbow trout, Oncorhyncus mykiss,were exposed to 10, 50 or 100 ng/L ethynylestradiol (a xeno-estrogen) for 7 days. Following exposure hepatic RNA was extracted. Fluorescently labeled cDNA were generated and hybridized against a commercially available Atlantic Salmon/Trout array (GRASP project, University of Victoria) spotted with 16,000 cDNAs. Transcript expression in treated vs control fish was analyzed via Genespring (Silicon Genetics) to identify genes with altered expression, as well as to determine gene clustering patterns that can be used as "expression signatures". Array results were confirmed via qRT PCR. Our analysis indicates that gene expression profiles varied somewhat with dose. Established biomarkers of exposure to estrogenic chemicals, such as vitellogenin, vitelline envelope proteins, and the estrogen receptor alpha, were induced at every dose. Other genes were dose specific, suggesting that different doses induce distinct physiological responses. These findings demonstrate that cDNA microarrays could be used to identify both toxicant class and relative dose.

A typology of pain coping strategies in pediatric patients with chronic abdominal pain.

PubMed

Walker, Lynn S; Baber, Kari Freeman; Garber, Judy; Smith, Craig A

2008-07-15

This study aimed to identify clinically meaningful profiles of pain coping strategies used by youth with chronic abdominal pain (CAP). Participants (n=699) were pediatric patients (ages 8-18 years) and their parents. Patients completed the Pain Response Inventory (PRI) and measures of somatic and depressive symptoms, disability, pain severity and pain efficacy, and perceived competence. Parents rated their children's pain severity and coping efficacy. Hierarchical cluster analysis based on the 13 PRI subscales identified pain coping profiles in Sample 1 (n=311) that replicated in Sample 2 (n=388). Evidence was found of external validity and distinctiveness of the profiles. The findings support a typology of pain coping that reflects the quality of patients' pain mastery efforts and interpersonal relationships associated with pain coping. Results are discussed in relation to developmental processes, attachment styles, and treatment implications.

Molecular events of apical bud formation in white spruce, Picea glauca.

PubMed

El Kayal, Walid; Allen, Carmen C G; Ju, Chelsea J-T; Adams, Eri; King-Jones, Susanne; Zaharia, L Irina; Abrams, Suzanne R; Cooke, Janice E K

2011-03-01

Bud formation is an adaptive trait that temperate forest trees have acquired to facilitate seasonal synchronization. We have characterized transcriptome-level changes that occur during bud formation of white spruce [Picea glauca (Moench) Voss], a primarily determinate species in which preformed stem units contained within the apical bud constitute most of next season's growth. Microarray analysis identified 4460 differentially expressed sequences in shoot tips during short day-induced bud formation. Cluster analysis revealed distinct temporal patterns of expression, and functional classification of genes in these clusters implied molecular processes that coincide with anatomical changes occurring in the developing bud. Comparing expression profiles in developing buds under long day and short day conditions identified possible photoperiod-responsive genes that may not be essential for bud development. Several genes putatively associated with hormone signalling were identified, and hormone quantification revealed distinct profiles for abscisic acid (ABA), cytokinins, auxin and their metabolites that can be related to morphological changes to the bud. Comparison of gene expression profiles during bud formation in different tissues revealed 108 genes that are differentially expressed only in developing buds and show greater transcript abundance in developing buds than other tissues. These findings provide a temporal roadmap of bud formation in white spruce. © 2011 Blackwell Publishing Ltd.

Integrative “omic” analysis reveals distinctive cold responses in leaves and roots of strawberry, Fragaria × ananassa ‘Korona’

PubMed Central

Koehler, Gage; Rohloff, Jens; Wilson, Robert C.; Kopka, Joachim; Erban, Alexander; Winge, Per; Bones, Atle M.; Davik, Jahn; Alsheikh, Muath K.; Randall, Stephen K.

2015-01-01

To assess underlying metabolic processes and regulatory mechanisms during cold exposure of strawberry, integrative “omic” approaches were applied to Fragaria × ananassa Duch. ‘Korona.’ Both root and leaf tissues were examined for responses to the cold acclimation processes. Levels of metabolites, proteins, and transcripts in tissues from plants grown at 18°C were compared to those following 1–10 days of cold (2°C) exposure. When leaves and roots were subjected to GC/TOF-MS-based metabolite profiling, about 160 compounds comprising mostly structurally annotated primary and secondary metabolites, were found. Overall, ‘Korona’ showed a modest increase of protective metabolites such as amino acids (aspartic acid, leucine, isoleucine, and valine), pentoses, phosphorylated and non-phosphorylated hexoses, and distinct compounds of the raffinose pathway (galactinol and raffinose). Distinctive responses were observed in roots and leaves. By 2DE proteomics a total of 845 spots were observed in leaves; 4.6% changed significantly in response to cold. Twenty-one proteins were identified, many of which were associated with general metabolism or photosynthesis. Transcript levels in leaves were determined by microarray, where dozens of cold associated transcripts were quantitatively characterized, and levels of several potential key contributors (e.g., the dehydrin COR47 and GADb) to cold tolerance were confirmed by qRT-PCR. Cold responses are placed within the existing knowledge base of low temperature-induced changes in plants, allowing an evaluation of the uniqueness or generality of Fragaria responses in photosynthetic tissues. Overall, the cold response characteristics of ‘Korona’ are consistent with a moderately cold tolerant plant. PMID:26528299

Genome-wide gene expression profiling suggests distinct radiation susceptibilities in sporadic and post-Chernobyl papillary thyroid cancers

PubMed Central

Detours, V; Delys, L; Libert, F; Weiss Solís, D; Bogdanova, T; Dumont, J E; Franc, B; Thomas, G; Maenhaut, C

2007-01-01

Papillary thyroid cancers (PTCs) incidence dramatically increased in the vicinity of Chernobyl. The cancer-initiating role of radiation elsewhere is debated. Therefore, we searched for a signature distinguishing radio-induced from sporadic cancers. Using microarrays, we compared the expression profiles of PTCs from the Chernobyl Tissue Bank (CTB, n=12) and from French patients with no history of exposure to ionising radiations (n=14). We also compared the transcriptional responses of human lymphocytes to the presumed aetiological agents initiating these tumours, γ-radiation and H2O2. On a global scale, the transcriptomes of CTB and French tumours are indistinguishable, and the transcriptional responses to γ-radiation and H2O2 are similar. On a finer scale, a 118 genes signature discriminated the γ-radiation and H2O2 responses. This signature could be used to classify the tumours as CTB or French with an error of 15–27%. Similar results were obtained with an independent signature of 13 genes involved in homologous recombination. Although sporadic and radio-induced PTCs represent the same disease, they are distinguishable with molecular signatures reflecting specific responses to γ-radiation and H2O2. These signatures in PTCs could reflect the susceptibility profiles of the patients, suggesting the feasibility of a radiation susceptibility test. PMID:17712314

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

PubMed

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

2012-05-15

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

Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers

PubMed Central

Bloom, Chloe I.; Graham, Christine M.; Berry, Matthew P. R.; Rozakeas, Fotini; Redford, Paul S.; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A.; Wilkinson, Robert J.; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-pei; Lipman, Marc; O’Garra, Anne

2013-01-01

Rationale New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment. PMID:23940611

Enhanced FCGR2A and FCGR3A signaling by HIV viremic controller IgG

PubMed Central

Alvarez, Raymond A.; Maestre, Ana M.; Durham, Natasha D.; Barria, Maria Ines; Ishii-Watabe, Akiko; Tada, Minoru; Hotta, Mathew T.; Rodriguez-Caprio, Gabriela; Fierer, Daniel S.; Fernandez-Sesma, Ana; Simon, Viviana; Chen, Benjamin K.

2017-01-01

HIV-1 viremic controllers (VC) spontaneously control infection without antiretroviral treatment. Several studies indicate that IgG Abs from VCs induce enhanced responses from immune effector cells. Since signaling through Fc-γ receptors (FCGRs) modulate these Ab-driven responses, here we examine if enhanced FCGR activation is a common feature of IgG from VCs. Using an infected cell–based system, we observed that VC IgG stimulated greater FCGR2A and FCGR3A activation as compared with noncontrollers, independent of the magnitude of HIV-specific Ab binding or virus neutralization activities. Multivariate regression analysis showed that enhanced FCGR signaling was a significant predictor of VC status as compared with chronically infected patients (CIP) on highly active antiretroviral therapy (HAART). Unsupervised hierarchical clustering of patient IgG functions primarily grouped VC IgG profiles by enhanced FCGR2A, FCGR3A, or dual signaling activity. Our findings demonstrate that enhanced FCGR signaling is a common and significant predictive feature of VC IgG, with VCs displaying a distinct spectrum of FCGR activation profiles. Thus, profiling FCGR activation may provide a useful method for screening and distinguishing protective anti-HIV IgG responses in HIV-infected patients and in monitoring HIV vaccination regimens. PMID:28239647

Distinct First Trimester Cytokine Profiles for Gestational Hypertension and Preeclampsia.

PubMed

Tangerås, Line H; Austdal, Marie; Skråstad, Ragnhild B; Salvesen, Kjell Å; Austgulen, Rigmor; Bathen, Tone F; Iversen, Ann-Charlotte

2015-11-01

Gestational hypertension and preeclampsia involve dysregulated maternal inflammatory responses to pregnancy, but whether such responses differ between the disorders has not been determined. We aimed to investigate disease-specific early pregnancy serum cytokine profiles of women subsequently developing gestational hypertension or preeclampsia for new insight into the underlying pathogeneses and differences between the disorders. The study cohort consisted of 548 pregnant Norwegian women who were either multiparous with previous gestational hypertension or preeclampsia or were nulliparous. Maternal sera at gestational weeks 11(0)-13(6) were assayed for 27 cytokines, C-reactive protein, total cholesterol, high-density lipoprotein, triglyceride, creatinine, calcium, uric acid, and placental growth factor. Compared with normotensive women, women with both hypertensive conditions presented an atherogenic lipid profile at early gestation, but only those later developing gestational hypertension had significantly higher serum levels of interleukin (IL)-5 and IL-12. Comparing the 2 hypertensive pregnancy disorders, women subsequently developing gestational hypertension had higher serum levels of IL-1β, IL-5, IL-7, IL-8, IL-13, basic fibroblast growth factor, and vascular endothelial growth factor than the women subsequently developing preeclampsia. This study identifies early pregnancy differences in serum cytokine profiles for gestational hypertension and preeclampsia. © 2015 American Heart Association, Inc.

The KIM-family protein-tyrosine phosphatases use distinct reversible oxidation intermediates: Intramolecular or intermolecular disulfide bond formation.

PubMed

Machado, Luciana E S F; Shen, Tun-Li; Page, Rebecca; Peti, Wolfgang

2017-05-26

The kinase interaction motif (KIM) family of protein-tyrosine phosphatases (PTPs) includes hematopoietic protein-tyrosine phosphatase (HePTP), striatal-enriched protein-tyrosine phosphatase (STEP), and protein-tyrosine phosphatase receptor type R (PTPRR). KIM-PTPs bind and dephosphorylate mitogen-activated protein kinases (MAPKs) and thereby critically modulate cell proliferation and differentiation. PTP activity can readily be diminished by reactive oxygen species (ROS), e.g. H 2 O 2 , which oxidize the catalytically indispensable active-site cysteine. This initial oxidation generates an unstable sulfenic acid intermediate that is quickly converted into either a sulfinic/sulfonic acid (catalytically dead and irreversible inactivation) or a stable sulfenamide or disulfide bond intermediate (reversible inactivation). Critically, our understanding of ROS-mediated PTP oxidation is not yet sufficient to predict the molecular responses of PTPs to oxidative stress. However, identifying distinct responses will enable novel routes for PTP-selective drug design, important for managing diseases such as cancer and Alzheimer's disease. Therefore, we performed a detailed biochemical and molecular study of all KIM-PTP family members to determine their H 2 O 2 oxidation profiles and identify their reversible inactivation mechanism(s). We show that despite having nearly identical 3D structures and sequences, each KIM-PTP family member has a unique oxidation profile. Furthermore, we also show that whereas STEP and PTPRR stabilize their reversibly oxidized state by forming an intramolecular disulfide bond, HePTP uses an unexpected mechanism, namely, formation of a reversible intermolecular disulfide bond. In summary, despite being closely related, KIM-PTPs significantly differ in oxidation profiles. These findings highlight that oxidation protection is critical when analyzing PTPs, for example, in drug screening. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Norway spruce embryogenesis: changes in carbohydrate profile, structural development and response to polyethylene glycol

PubMed Central

Hudec, Lukáš; Konrádová, Hana; Hašková, Anna; Lipavská, Helena

2016-01-01

Two unrelated, geographically distinct, highly embryogenic lines of Norway spruce (Picea abies (L.) Karst.) were analysed to identify metabolic traits characteristic for lines with good yields of high-quality embryos. The results were compared with corresponding characteristics of a poorly productive line (low embryo yield, scarce high-quality embryos). The following carbohydrate profiles and spectra during maturation, desiccation and germination were identified as promising characteristics for line evaluation: a gradual decrease in total soluble carbohydrates with an increasing sucrose : hexose ratio during maturation; accumulation of raffinose family oligosaccharides resulting from desiccation and their rapid degradation at the start of germination; and a decrease in sucrose, increase in hexoses and the appearance of pinitol with proceeding germination. We propose that any deviation from this profile in an embryonic line is a symptom of inferior somatic embryo development. We further propose that a fatty acid spectrum dominated by linoleic acid (18 : 2) was a common feature of healthy spruce somatic embryos, although it was quite different from zygotic embryos mainly containing oleic acid (18 : 1). The responses of the lines to osmotic stress were evaluated based on comparison of control (without osmoticum) and polyethylene glycol (PEG)-exposed (PEG 4000) variants. Although genetically distinct, both highly embryogenic lines responded in a very similar manner, with the only difference being sensitivity to high concentrations of PEG. At an optimum PEG concentration (3.75 and 5%), which was line specific, negative effects of PEG on embryo germination were compensated for by a higher maturation efficiency so that the application of PEG at an appropriate concentration improved the yield of healthy germinants per gram of initial embryonal mass and accelerated the process. Polyethylene glycol application, however, resulted in no improvement of the poorly productive line. PMID:27052433

Monocyte migration explains the changes in macrophage arachidonate metabolism during the immune response.

PubMed Central

Tripp, C S; Unanue, E R; Needleman, P

1986-01-01

The profile of arachidonic acid metabolites in resident peritoneal macrophages is distinctly different from the profile of macrophages isolated after an acute bacterial infection. The latter produce decreased prostaglandins E2 and I2 and leukotriene C4 while conserving the synthesis of thromboxane A2. We show here that the initial changes in peritoneal macrophage arachidonate metabolism during the immune response appear to be the result of the large influx of blood monocytes, which have a characteristic metabolism distinct from resident macrophages. We demonstrate that the initial decrease in peritoneal macrophage arachidonate metabolism and the increase in macrophage numbers occur simultaneously after infection with Listeria monocytogenes. Also the macrophage arachidonate metabolism seen at the height of the peritoneal cellular influx is the same as that of purified blood monocytes. Both Listeria peritoneal macrophages and blood monocytes produce equal or greater quantities of thromboxane A2 relative to prostaglandins I2 and E2 or leukotriene C4 whereas resident cells produce 1/10 to 1/25 as much thromboxane A2 compared to the other products. Furthermore, the changes in peritoneal macrophage arachidonate metabolism in response to Listeria infection do not occur if the influx of blood monocytes is stopped by irradiating the mice prior to infection implying that the cellular influx is necessary to see the changes in arachidonate metabolism. Finally, activation of peritoneal macrophages, measured as an increase in Ia expression, occurs 36 hr after the influx of monocytes from the blood and the resultant shift in arachidonate metabolism during Listeria infection. PMID:3099288

Changes in the transcriptomic profiles of maize roots in response to iron-deficiency stress.

PubMed

Li, Yan; Wang, Nian; Zhao, Fengtao; Song, Xuejiao; Yin, Zhaohua; Huang, Rong; Zhang, Chunqing

2014-07-01

Plants are often subjected to iron (Fe)-deficiency stress because of its low solubility. Plants have evolved two distinct strategies to solubilize and transport Fe to acclimate to this abiotic stress condition. Transcriptomic profiling analysis was performed using Illumina digital gene expression to understand the mechanism underlying resistance responses of roots to Fe starvation in maize, an important Strategy II plant. A total of 3,427, 4,069, 4,881, and 2,610 genes had significantly changed expression levels after Fe-deficiency treatments of 1, 2, 4 or 7 days, respectively. Genes involved in 2'-deoxymugineic acid (DMA) synthesis, secretion, and Fe(III)-DMA uptake were significantly induced. Many genes related to plant hormones, protein kinases, and protein phosphatases responded to Fe-deficiency stress, suggesting their regulatory roles in response to the Fe-deficiency stress. Functional annotation clustering analysis, using the Database for Annotation, Visualization and Integrated Discovery, revealed maize root responses to Fe starvation. This resulted in 38 functional annotation clusters: 25 for up-regulated genes, and 13 for down-regulated ones. These included genes encoding enzymes involved in the metabolism of carboxylic acids, isoprenoids and aromatic compounds, transporters, and stress response proteins. Our work provides integrated information for understanding maize response to Fe-deficiency stress.

COPPER RESPONSE REGULATOR1–Dependent and –Independent Responses of the Chlamydomonas reinhardtii Transcriptome to Dark Anoxia[W

PubMed Central

Hemschemeier, Anja; Casero, David; Liu, Bensheng; Benning, Christoph; Pellegrini, Matteo; Happe, Thomas; Merchant, Sabeeha S.

2013-01-01

Anaerobiosis is a stress condition for aerobic organisms and requires extensive acclimation responses. We used RNA-Seq for a whole-genome view of the acclimation of Chlamydomonas reinhardtii to anoxic conditions imposed simultaneously with transfer to the dark. Nearly 1.4 × 103 genes were affected by hypoxia. Comparing transcript profiles from early (hypoxic) with those from late (anoxic) time points indicated that cells activate oxidative energy generation pathways before employing fermentation. Probable substrates include amino acids and fatty acids (FAs). Lipid profiling of the C. reinhardtii cells revealed that they degraded FAs but also accumulated triacylglycerols (TAGs). In contrast with N-deprived cells, the TAGs in hypoxic cells were enriched in desaturated FAs, suggesting a distinct pathway for TAG accumulation. To distinguish transcriptional responses dependent on COPPER RESPONSE REGULATOR1 (CRR1), which is also involved in hypoxic gene regulation, we compared the transcriptomes of crr1 mutants and complemented strains. In crr1 mutants, ∼40 genes were aberrantly regulated, reaffirming the importance of CRR1 for the hypoxic response, but indicating also the contribution of additional signaling strategies to account for the remaining differentially regulated transcripts. Based on transcript patterns and previous results, we conclude that nitric oxide–dependent signaling cascades operate in anoxic C. reinhardtii cells. PMID:24014546

Movements of Diadromous Fish in Large Unregulated Tropical Rivers Inferred from Geochemical Tracers

PubMed Central

Walther, Benjamin D.; Dempster, Tim; Letnic, Mike; McCulloch, Malcolm T.

2011-01-01

Patterns of migration and habitat use in diadromous fishes can be highly variable among individuals. Most investigations into diadromous movement patterns have been restricted to populations in regulated rivers, and little information exists for those in unregulated catchments. We quantified movements of migratory barramundi Lates calcarifer (Bloch) in two large unregulated rivers in northern Australia using both elemental (Sr/Ba) and isotope (87Sr/86Sr) ratios in aragonitic ear stones, or otoliths. Chemical life history profiles indicated significant individual variation in habitat use, particularly among chemically distinct freshwater habitats within a catchment. A global zoning algorithm was used to quantify distinct changes in chemical signatures across profiles. This algorithm identified between 2 and 6 distinct chemical habitats in individual profiles, indicating variable movement among habitats. Profiles of 87Sr/86Sr ratios were notably distinct among individuals, with highly radiogenic values recorded in some otoliths. This variation suggested that fish made full use of habitats across the entire catchment basin. Our results show that unrestricted movement among freshwater habitats is an important component of diadromous life histories for populations in unregulated systems. PMID:21494693

Molecular classification and molecular forecasting of breast cancer: ready for clinical application?

PubMed

Brenton, James D; Carey, Lisa A; Ahmed, Ahmed Ashour; Caldas, Carlos

2005-10-10

Profiling breast cancer with expression arrays has become common, and it has been suggested that the results from early studies will lead to understanding of the molecular differences between clinical cases and allow individualization of care. We critically review two main applications of expression profiling; studies unraveling novel breast cancer classifications and those that aim to identify novel markers for prediction of clinical outcome. Breast cancer may now be subclassified into luminal, basal, and HER2 subtypes with distinct differences in prognosis and response to therapy. However, profiling studies to identify predictive markers have suffered from methodologic problems that prevent general application of their results. Future work will need to reanalyze existing microarray data sets to identify more representative sets of candidate genes for use as prognostic signatures and will need to take into account the new knowledge of molecular subtypes of breast cancer when assessing predictive effects.

Drought and flooding have distinct effects on herbivore-induced responses and resistance in Solanum dulcamara.

PubMed

Nguyen, Duy; D'Agostino, Nunzio; Tytgat, Tom O G; Sun, Pulu; Lortzing, Tobias; Visser, Eric J W; Cristescu, Simona M; Steppuhn, Anke; Mariani, Celestina; van Dam, Nicole M; Rieu, Ivo

2016-07-01

In the field, biotic and abiotic stresses frequently co-occur. As a consequence, common molecular signalling pathways governing adaptive responses to individual stresses can interact, resulting in compromised phenotypes. How plant signalling pathways interact under combined stresses is poorly understood. To assess this, we studied the consequence of drought and soil flooding on resistance of Solanum dulcamara to Spodoptera exigua and their effects on hormonal and transcriptomic profiles. The results showed that S. exigua larvae performed less well on drought-stressed plants than on well-watered and flooded plants. Both drought and insect feeding increased abscisic acid and jasmonic acid (JA) levels, whereas flooding did not induce JA accumulation. RNA sequencing analyses corroborated this pattern: drought and herbivory induced many biological processes that were repressed by flooding. When applied in combination, drought and herbivory had an additive effect on specific processes involved in secondary metabolism and defence responses, including protease inhibitor activity. In conclusion, drought and flooding have distinct effects on herbivore-induced responses and resistance. Especially, the interaction between abscisic acid and JA signalling may be important to optimize plant responses to combined drought and insect herbivory, making drought-stressed plants more resistant to insects than well-watered and flooded plants. © 2016 John Wiley & Sons Ltd.

Salmonella enterica serovar-specific transcriptional reprogramming of infected cells.

PubMed

Hannemann, Sebastian; Galán, Jorge E

2017-07-01

Despite their high degree of genomic similarity, different Salmonella enterica serovars are often associated with very different clinical presentations. In humans, for example, the typhoidal S. enterica serovar Typhi causes typhoid fever, a life-threatening systemic disease. In contrast, the non-typhoidal S. enterica serovar Typhimurium causes self-limiting gastroenteritis. The molecular bases for these different clinical presentations are incompletely understood. The ability to re-program gene expression in host cells is an essential virulence factor for typhoidal and non-typhoidal S. enterica serovars. Here, we have compared the transcriptional profile of cultured epithelial cells infected with S. Typhimurium or S. Typhi. We found that both serovars stimulated distinct transcriptional responses in infected cells that are associated with the stimulation of specific signal transduction pathways. These specific responses were associated with the presence of a distinct repertoire of type III secretion effector proteins. These observations provide major insight into the molecular bases for potential differences in the pathogenic mechanisms of typhoidal and non-typhoidal S. enterica serovars.

Distinct gene expression profiles in peripheral blood mononuclear cells from patients infected with vaccinia virus, yellow fever 17D virus, or upper respiratory infections.

PubMed

Scherer, Christina A; Magness, Charles L; Steiger, Kathryn V; Poitinger, Nicholas D; Caputo, Christine M; Miner, Douglas G; Winokur, Patricia L; Klinzman, Donna; McKee, Janice; Pilar, Christine; Ward, Patricia A; Gillham, Martha H; Haulman, N Jean; Stapleton, Jack T; Iadonato, Shawn P

2007-08-29

Gene expression in human peripheral blood mononuclear cells was systematically evaluated following smallpox and yellow fever vaccination, and naturally occurring upper respiratory infection (URI). All three infections were characterized by the induction of many interferon stimulated genes, as well as enhanced expression of genes involved in proteolysis and antigen presentation. Vaccinia infection was also characterized by a distinct expression signature composed of up-regulation of monocyte response genes, with repression of genes expressed by B and T-cells. In contrast, the yellow fever host response was characterized by a suppression of ribosomal and translation factors, distinguishing this infection from vaccinia and URI. No significant URI-specific signature was observed, perhaps reflecting greater heterogeneity in the study population and etiological agents. Taken together, these data suggest that specific host gene expression signatures may be identified that distinguish one or a small number of virus agents.

Amygdala activation in response to facial expressions in pediatric obsessive-compulsive disorder

PubMed Central

Britton, Jennifer C.; Stewart, S. Evelyn; Killgore, William D.S.; Rosso, Isabelle M.; Price, Lauren M.; Gold, Andrea L.; Pine, Daniel S.; Wilhelm, Sabine; Jenike, Michael A.; Rauch, Scott L.

2010-01-01

Background Exaggerated amygdala activation to threatening faces has been detected in adults and children with anxiety disorders, compared to healthy comparison subjects. However, the profile of amygdala activation in response to facial expressions in obsessive-compulsive disorder (OCD) may be a distinguishing feature; a prior study found that compared with healthy adults, adults with OCD exhibited less amygdala activation to emotional and neutral faces, relative to fixation (Cannistraro et al., 2004). Methods In the current event-related functional magnetic resonance imaging (fMRI) study, a pediatric OCD sample (N=12) and a healthy comparison sample (HC, N=17) performed a gender discrimination task while viewing emotional faces (happy, fear, disgust) and neutral faces. Results Compared to the HC group, the OCD group showed less amygdala/hippocampus activation in all emotion and neutral conditions relative to fixation. Conclusions Like previous reports in adult OCD, pediatric OCD may have a distinct neural profile from other anxiety disorders, with respect to amygdala activation in response to emotional stimuli that are not disorder-specific. PMID:20602430

Psychological profiling of offender characteristics from crime behaviors in serial rape offences.

PubMed

Kocsis, Richard N; Cooksey, Ray W; Irwin, Harvey J

2002-04-01

Criminal psychological profiling has progressively been incorporated into police procedures despite a dearth of empirical research. Indeed, in the study of serial violent crimes for the purpose of psychological profiling, very few original, quantitative, academically reviewed studies actually exist. This article reports on the analysis of 62 incidents of serial sexual assault. The statistical procedure of multidimensional scaling was employed in the analysis of this data, which in turn produced a five-cluster model of serial rapist behavior. First, a central cluster of behaviors were identified that represent common behaviors to all patterns of serial rape. Second, four distinct outlying patterns were identified as demonstrating distinct offence styles, these being assigned the following descriptive labels brutality, intercourse, chaotic, and ritual. Furthermore, analysis of these patterns also identified distinct offender characteristics that allow for the use of empirically robust offender profiles in future serial rape investigations.

Non-digestible oligosaccharides directly regulate host kinome to modulate host inflammatory responses without alterations in the gut microbiota.

PubMed

Wu, Richard Y; Määttänen, Pekka; Napper, Scott; Scruten, Erin; Li, Bo; Koike, Yuhki; Johnson-Henry, Kathene C; Pierro, Agostino; Rossi, Laura; Botts, Steven R; Surette, Michael G; Sherman, Philip M

2017-10-10

Prebiotics are non-digestible food ingredients that enhance the growth of certain microbes within the gut microbiota. Prebiotic consumption generates immune-modulatory effects that are traditionally thought to reflect microbial interactions within the gut. However, recent evidence suggests they may also impart direct microbe-independent effects on the host, though the mechanisms of which are currently unclear. Kinome arrays were used to profile the host intestinal signaling responses to prebiotic exposures in the absence of microbes. Identified pathways were functionally validated in Caco-2Bbe1 intestinal cell line and in vivo model of murine endotoxemia. We found that prebiotics directly regulate host mucosal signaling to alter response to bacterial infection. Intestinal epithelial cells (IECs) exposed to prebiotics are hyporesponsive to pathogen-induced mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) activations, and have a kinome profile distinct from non-treated cells pertaining to multiple innate immune signaling pathways. Consistent with this finding, mice orally gavaged with prebiotics showed dampened inflammatory response to lipopolysaccharide (LPS) without alterations in the gut microbiota. These findings provide molecular mechanisms of direct host-prebiotic interactions to support prebiotics as potent modulators of host inflammation.

Distinct retrosplenial cortex cell populations and their spike dynamics during ketamine-induced unconscious state

PubMed Central

Zhao, Fang; Tsien, Joe Z.

2017-01-01

Ketamine is known to induce psychotic-like symptoms, including delirium and visual hallucinations. It also causes neuronal damage and cell death in the retrosplenial cortex (RSC), an area that is thought to be a part of high visual cortical pathways and at least partially responsible for ketamine’s psychotomimetic activities. However, the basic physiological properties of RSC cells as well as their response to ketamine in vivo remained largely unexplored. Here, we combine a computational method, the Inter-Spike Interval Classification Analysis (ISICA), and in vivo recordings to uncover and profile excitatory cell subtypes within layers 2&3 and 5&6 of the RSC in mice within both conscious, sleep, and ketamine-induced unconscious states. We demonstrate two distinct excitatory principal cell sub-populations, namely, high-bursting excitatory principal cells and low-bursting excitatory principal cells, within layers 2&3, and show that this classification is robust over the conscious states, namely quiet awake, and natural unconscious sleep periods. Similarly, we provide evidence of high-bursting and low-bursting excitatory principal cell sub-populations within layers 5&6 that remained distinct during quiet awake and sleep states. We further examined how these subtypes are dynamically altered by ketamine. During ketamine-induced unconscious state, these distinct excitatory principal cell subtypes in both layer 2&3 and layer 5&6 exhibited distinct dynamics. We also uncovered different dynamics of local field potential under various brain states in layer 2&3 and layer 5&6. Interestingly, ketamine administration induced high gamma oscillations in layer 2&3 of the RSC, but not layer 5&6. Our results show that excitatory principal cells within RSC layers 2&3 and 5&6 contain multiple physiologically distinct sub-populations, and they are differentially affected by ketamine. PMID:29073221

Distinct retrosplenial cortex cell populations and their spike dynamics during ketamine-induced unconscious state.

PubMed

Fox, Grace E; Li, Meng; Zhao, Fang; Tsien, Joe Z

2017-01-01

Ketamine is known to induce psychotic-like symptoms, including delirium and visual hallucinations. It also causes neuronal damage and cell death in the retrosplenial cortex (RSC), an area that is thought to be a part of high visual cortical pathways and at least partially responsible for ketamine's psychotomimetic activities. However, the basic physiological properties of RSC cells as well as their response to ketamine in vivo remained largely unexplored. Here, we combine a computational method, the Inter-Spike Interval Classification Analysis (ISICA), and in vivo recordings to uncover and profile excitatory cell subtypes within layers 2&3 and 5&6 of the RSC in mice within both conscious, sleep, and ketamine-induced unconscious states. We demonstrate two distinct excitatory principal cell sub-populations, namely, high-bursting excitatory principal cells and low-bursting excitatory principal cells, within layers 2&3, and show that this classification is robust over the conscious states, namely quiet awake, and natural unconscious sleep periods. Similarly, we provide evidence of high-bursting and low-bursting excitatory principal cell sub-populations within layers 5&6 that remained distinct during quiet awake and sleep states. We further examined how these subtypes are dynamically altered by ketamine. During ketamine-induced unconscious state, these distinct excitatory principal cell subtypes in both layer 2&3 and layer 5&6 exhibited distinct dynamics. We also uncovered different dynamics of local field potential under various brain states in layer 2&3 and layer 5&6. Interestingly, ketamine administration induced high gamma oscillations in layer 2&3 of the RSC, but not layer 5&6. Our results show that excitatory principal cells within RSC layers 2&3 and 5&6 contain multiple physiologically distinct sub-populations, and they are differentially affected by ketamine.

Symptom-Hemodynamic Mismatch and Heart Failure Event Risk

PubMed Central

Lee, Christopher S.; Hiatt, Shirin O.; Denfeld, Quin E.; Mudd, James O.; Chien, Christopher; Gelow, Jill M.

2014-01-01

Background Heart failure (HF) is a heterogeneous condition of both symptoms and hemodynamics. Objective The goal of this study was to identify distinct profiles among integrated data on physical and psychological symptoms and hemodynamics, and quantify differences in 180-day event-risk among observed profiles. Methods A secondary analysis of data collected during two prospective cohort studies by a single group of investigators was performed. Latent class mixture modeling was used to identify distinct symptom-hemodynamic profiles. Cox proportional hazards modeling was used to quantify difference in event-risk (HF emergency visit, hospitalization or death) among profiles. Results The mean age (n=291) was 57±13 years, 38% were female, and 61% had class III/IV HF. Three distinct symptom-hemodynamic profiles were identified. 17.9% of patients had concordant symptoms and hemodynamics (i.e. moderate physical and psychological symptoms matched the comparatively hemodynamic profile), 17.9% had severe symptoms and average hemodynamics, and 64.2% had poor hemodynamics and mild symptoms. Compared to those in the concordant profile, both profiles of symptom-hemodynamic mismatch were associated with a markedly increased event-risk (severe symptoms hazards ratio = 3.38, p=0.033; poor hemodynamics hazards ratio = 3.48, p=0.016). Conclusions A minority of adults with HF have concordant symptoms and hemodynamics. Either profile of symptom-hemodynamic mismatch in HF is associated with a greater risk of healthcare utilization for HF or death. PMID:24988323

Multicomponent Calibration and Quantitation Methods.

DTIC Science & Technology

1984-11-01

liquid chromatographic peaks (45). Applying rank annihilation to LC /UV data requires that the elution profiles of each individual component in the...measurements, e.g. LC /UV, CC/MS, or GC/FTIR analyses. The response of a single component can be described as M = a x y’ (45) 0 where M contains the...in the second dimension. For example, a GC/MS peak consisting - 3 of 50 mass spectra each composed of 20 distinct m/e ratios would result in a matrix

Adolescent Coping Profiles Differentiate Reports of Depression and Anxiety Symptoms

PubMed Central

Herres, Joanna; Ohannessian, Christine McCauley

2015-01-01

The purpose of the study was to identify groups of adolescents based on their reported use of different coping strategies and compare levels of depression and anxiety symptoms across the groups. Tenth and eleventh grade public school students (N = 982; 51% girls; 66% Caucasian; M age =16.04, SD = .73) completed a battery of self-report measures that assessed their use of different coping strategies, depressive symptoms, and anxiety symptoms. Latent profile analysis (LPA) classified the participants into four distinct groups based on their responses on subscales of the COPE inventory (Carver, Scheier, & Weintraub, 1989). Groups differed in amount of coping with participants in each group showing relative preference for engaging in certain strategies over others. Disengaged copers reported the lowest amounts of coping with a preference for avoidance strategies. Independent copers reported moderate levels of coping with relatively less use of support-seeking. Social support-seeking copers and active copers reported the highest levels of coping with a particular preference for support-seeking strategies. The independent copers reported the lowest levels of depressive symptoms compared to the three other groups. The Social Support Seeking and Active Coping Groups reported the highest levels of anxiety. Although distinct coping profiles were observed, findings showed that adolescents between the ages of 14 and 16 engage in multiple coping strategies and are more likely to vary in their amount of coping than in their use of specific strategies. PMID:26275359

Dose–response relationships in gene expression profiles in rainbow trout, Oncorhyncus mykiss, exposed to ethynylestradiol

PubMed Central

Hook, Sharon E.; Skillman, Ann D.; Small, Jack A.; Schultz, Irvin R.

2008-01-01

Determining how gene expression profiles change with toxicant dose will improve the utility of arrays in identifying biomarkers and modes of toxic action. Isogenic rainbow trout, Oncorhyncus mykiss, were exposed to 10, 50 or 100 ng/L ethynylestradiol (a xeno-estrogen) for 7 days. Following exposure hepatic RNA was extracted. Fluorescently labeled cDNA were generated and hybridized against a commercially available Atlantic Salmon/Trout array (GRASP project, University of Victoria) spotted with 16,000 cDNAs. Transcript expression in treated vs control fish was analyzed via Genespring (Silicon Genetics) to identify genes with altered expression, as well as to determine gene clustering patterns that can be used as “expression signatures”. Array results were confirmed via qRT PCR. Our analysis indicates that gene expression profiles varied somewhat with dose. Established biomarkers of exposure to estrogenic chemicals, such as vitellogenin, vitelline envelope proteins, and the estrogen receptor alpha, were induced at every dose. Other genes were dose specific, suggesting that diffierent doses induce distinct physiological responses. These findings demonstrate that cDNA microarrays could be used to identify both toxicant class and relative dose. PMID:16725192

Time-Resolved Transcriptome Analysis of Bacillus subtilis Responding to Valine, Glutamate, and Glutamine

PubMed Central

Ye, Bang-Ce; Zhang, Yan; Yu, Hui; Yu, Wen-Bang; Liu, Bao-Hong; Yin, Bin-Cheng; Yin, Chun-Yun; Li, Yuan-Yuan; Chu, Ju; Zhang, Si-Liang

2009-01-01

Microorganisms can restructure their transcriptional output to adapt to environmental conditions by sensing endogenous metabolite pools. In this paper, an Agilent customized microarray representing 4,106 genes was used to study temporal transcript profiles of Bacillus subtilis in response to valine, glutamate and glutamine pulses over 24 h. A total of 673, 835, and 1135 amino-acid-regulated genes were identified having significantly changed expression at one or more time points in response to valine, glutamate, and glutamine, respectively, including genes involved in cell wall, cellular import, metabolism of amino-acids and nucleotides, transcriptional regulation, flagellar motility, chemotaxis, phage proteins, sporulation, and many genes of unknown function. Different amino acid treatments were compared in terms of both the global temporal profiles and the 5-minute quick regulations, and between-experiment differential genes were identified. The highlighted genes were analyzed based on diverse sources of gene functions using a variety of computational tools, including T-profiler analysis, and hierarchical clustering. The results revealed the common and distinct modes of action of these three amino acids, and should help to elucidate the specific signaling mechanism of each amino acid as an effector. PMID:19763274

Early molecular correlates of adverse events following yellow fever vaccination

PubMed Central

Chan, Candice Y.Y.; Chan, Kuan Rong; Chua, Camillus J.H.; nur Hazirah, Sharifah; Ghosh, Sujoy; Ooi, Eng Eong; Low, Jenny G.

2017-01-01

The innate immune response shapes the development of adaptive immunity following infections and vaccination. However, it can also induce symptoms such as fever and myalgia, leading to the possibility that the molecular basis of immunogenicity and reactogenicity of vaccination are inseparably linked. To test this possibility, we used the yellow fever live-attenuated vaccine (YFLAV) as a model to study the molecular correlates of reactogenicity or adverse events (AEs). We analyzed the outcome of 68 adults who completed a YFLAV clinical trial, of which 43 (63.2%) reported systemic AEs. Through whole-genome profiling of blood collected before and after YFLAV dosing, we observed that activation of innate immune genes at day 1, but not day 3 after vaccination, was directly correlated with AEs. These findings contrast with the gene expression profile at day 3 that we and others have previously shown to be correlated with immunogenicity. We conclude that although the innate immune response is a double-edged sword, its expression that induces AEs is temporally distinct from that which engenders robust immunity. The use of genomic profiling thus provides molecular insights into the biology of AEs that potentially forms a basis for the development of safer vaccines. PMID:28978802

Profiling of ARDS pulmonary edema fluid identifies a metabolically distinct subset.

PubMed

Rogers, Angela J; Contrepois, Kévin; Wu, Manhong; Zheng, Ming; Peltz, Gary; Ware, Lorraine B; Matthay, Michael A

2017-05-01

There is considerable biological and physiological heterogeneity among patients who meet standard clinical criteria for acute respiratory distress syndrome (ARDS). In this study, we tested the hypothesis that there exists a subgroup of ARDS patients who exhibit a metabolically distinct profile. We examined undiluted pulmonary edema fluid obtained at the time of endotracheal intubation from 16 clinically phenotyped ARDS patients and 13 control patients with hydrostatic pulmonary edema. Nontargeted metabolic profiling was carried out on the undiluted edema fluid. Univariate and multivariate statistical analyses including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were conducted to find discriminant metabolites. Seven-hundred and sixty unique metabolites were identified in the pulmonary edema fluid of these 29 patients. We found that a subset of ARDS patients (6/16, 38%) presented a distinct metabolic profile with the overrepresentation of 235 metabolites compared with edema fluid from the other 10 ARDS patients, whose edema fluid metabolic profile was indistinguishable from those of the 13 control patients with hydrostatic edema. This "high metabolite" endotype was characterized by higher concentrations of metabolites belonging to all of the main metabolic classes including lipids, amino acids, and carbohydrates. This distinct group with high metabolite levels in the edema fluid was also associated with a higher mortality rate. Thus metabolic profiling of the edema fluid of ARDS patients supports the hypothesis that there is considerable biological heterogeneity among ARDS patients who meet standard clinical and physiological criteria for ARDS. Copyright © 2017 the American Physiological Society.

Profiling of ARDS pulmonary edema fluid identifies a metabolically distinct subset

PubMed Central

Contrepois, Kévin; Wu, Manhong; Zheng, Ming; Peltz, Gary; Ware, Lorraine B.; Matthay, Michael A.

2017-01-01

There is considerable biological and physiological heterogeneity among patients who meet standard clinical criteria for acute respiratory distress syndrome (ARDS). In this study, we tested the hypothesis that there exists a subgroup of ARDS patients who exhibit a metabolically distinct profile. We examined undiluted pulmonary edema fluid obtained at the time of endotracheal intubation from 16 clinically phenotyped ARDS patients and 13 control patients with hydrostatic pulmonary edema. Nontargeted metabolic profiling was carried out on the undiluted edema fluid. Univariate and multivariate statistical analyses including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were conducted to find discriminant metabolites. Seven-hundred and sixty unique metabolites were identified in the pulmonary edema fluid of these 29 patients. We found that a subset of ARDS patients (6/16, 38%) presented a distinct metabolic profile with the overrepresentation of 235 metabolites compared with edema fluid from the other 10 ARDS patients, whose edema fluid metabolic profile was indistinguishable from those of the 13 control patients with hydrostatic edema. This “high metabolite” endotype was characterized by higher concentrations of metabolites belonging to all of the main metabolic classes including lipids, amino acids, and carbohydrates. This distinct group with high metabolite levels in the edema fluid was also associated with a higher mortality rate. Thus metabolic profiling of the edema fluid of ARDS patients supports the hypothesis that there is considerable biological heterogeneity among ARDS patients who meet standard clinical and physiological criteria for ARDS. PMID:28258106

Background and design of the profiling biobehavioral responses to mechanical support in advanced heart failure study.

PubMed

Lee, Christopher S; Mudd, James O; Gelow, Jill M; Nguyen, Thuan; Hiatt, Shirin O; Green, Jennifer K; Denfeld, Quin E; Bidwell, Julie T; Grady, Kathleen L

2014-01-01

Unexplained heterogeneity in response to ventricular assist device (VAD) implantation for the management of advanced heart failure impedes our ability to predict favorable outcomes, provide adequate patient and family education, and personalize monitoring and symptom management strategies. The purpose of this article was to describe the background and the design of a study entitled "Profiling Biobehavioral Responses to Mechanical Support in Advanced Heart Failure" (PREMISE). PREMISE is a prospective cohort study designed to (1) identify common and distinct trajectories of change in physical and psychological symptom burden; (2) characterize common trajectories of change in serum biomarkers of myocardial stress, systemic inflammation, and endothelial dysfunction; and (3) quantify associations between symptoms and biomarkers of pathogenesis in adults undergoing VAD implantation. Latent growth mixture modeling, including parallel process and cross-classification modeling, will be used to address the study aims and will entail identifying trajectories, quantifying associations between trajectories and both clinical and quality-of-life outcomes, and identifying predictors of favorable symptom and biomarker responses to VAD implantation. Research findings from the PREMISE study will be used to enhance shared patient and provider decision making and to shape a much-needed new breed of interventions and clinical management strategies that are tailored to differential symptom and pathogenic responses to VAD implantation.

Combination of automated high throughput platforms, flow cytometry, and hierarchical clustering to detect cell state.

PubMed

Kitsos, Christine M; Bhamidipati, Phani; Melnikova, Irena; Cash, Ethan P; McNulty, Chris; Furman, Julia; Cima, Michael J; Levinson, Douglas

2007-01-01

This study examined whether hierarchical clustering could be used to detect cell states induced by treatment combinations that were generated through automation and high-throughput (HT) technology. Data-mining techniques were used to analyze the large experimental data sets to determine whether nonlinear, non-obvious responses could be extracted from the data. Unary, binary, and ternary combinations of pharmacological factors (examples of stimuli) were used to induce differentiation of HL-60 cells using a HT automated approach. Cell profiles were analyzed by incorporating hierarchical clustering methods on data collected by flow cytometry. Data-mining techniques were used to explore the combinatorial space for nonlinear, unexpected events. Additional small-scale, follow-up experiments were performed on cellular profiles of interest. Multiple, distinct cellular profiles were detected using hierarchical clustering of expressed cell-surface antigens. Data-mining of this large, complex data set retrieved cases of both factor dominance and cooperativity, as well as atypical cellular profiles. Follow-up experiments found that treatment combinations producing "atypical cell types" made those cells more susceptible to apoptosis. CONCLUSIONS Hierarchical clustering and other data-mining techniques were applied to analyze large data sets from HT flow cytometry. From each sample, the data set was filtered and used to define discrete, usable states that were then related back to their original formulations. Analysis of resultant cell populations induced by a multitude of treatments identified unexpected phenotypes and nonlinear response profiles.

Response to traumatic brain injury neurorehabilitation through an artificial intelligence and statistics hybrid knowledge discovery from databases methodology.

PubMed

Gibert, Karina; García-Rudolph, Alejandro; García-Molina, Alberto; Roig-Rovira, Teresa; Bernabeu, Montse; Tormos, José María

2008-01-01

Develop a classificatory tool to identify different populations of patients with Traumatic Brain Injury based on the characteristics of deficit and response to treatment. A KDD framework where first, descriptive statistics of every variable was done, data cleaning and selection of relevant variables. Then data was mined using a generalization of Clustering based on rules (CIBR), an hybrid AI and Statistics technique which combines inductive learning (AI) and clustering (Statistics). A prior Knowledge Base (KB) is considered to properly bias the clustering; semantic constraints implied by the KB hold in final clusters, guaranteeing interpretability of the resultis. A generalization (Exogenous Clustering based on rules, ECIBR) is presented, allowing to define the KB in terms of variables which will not be considered in the clustering process itself, to get more flexibility. Several tools as Class panel graph are introduced in the methodology to assist final interpretation. A set of 5 classes was recommended by the system and interpretation permitted profiles labeling. From the medical point of view, composition of classes is well corresponding with different patterns of increasing level of response to rehabilitation treatments. All the patients initially assessable conform a single group. Severe impaired patients are subdivided in four profiles which clearly distinct response patterns. Particularly interesting the partial response profile, where patients could not improve executive functions. Meaningful classes were obtained and, from a semantics point of view, the results were sensibly improved regarding classical clustering, according to our opinion that hybrid AI & Stats techniques are more powerful for KDD than pure ones.

What is your patient’s cognitive profile? Three distinct subgroups of cognitive function in persons with heart failure

PubMed Central

Hawkins, Misty A.W.; Schaefer, Julie T.; Gunstad, John; Dolansky, Mary A.; Redle, Joseph D.; Josephson, Richard; Moore, Shirley M.; Hughes, Joel W.

2014-01-01

Purpose To determine whether patients with heart failure (HF) have distinct profiles of cognitive impairment. Background Cognitive impairment is common in HF. Recent work found three cognitive profiles in HF patients— (1) intact, (2) impaired, and (3) memory-impaired. We examined the reproducibility of these profiles and clarified mechanisms. Methods HF patients (68.6±9.7years; N=329) completed neuropsychological testing. Composite scores were created for cognitive domains and used to identify clusters via agglomerative-hierarchical cluster analysis. Results A 3-cluster solution emerged. Cluster 1 (n=109) had intact cognition. Cluster 2 (n=123) was impaired across all domains. Cluster 3 (n=97) had impaired memory only. Clusters differed in age, race, education, SES, IQ, BMI, and diabetes (ps ≤.026) but not in mood, anxiety, cardiovascular, or pulmonary disease (ps≥.118). Conclusions We replicated three distinct patterns of cognitive function in persons with HF. These profiles may help providers offer tailored care to patients with different cognitive and clinical needs. PMID:25510559

Sensory Processing in Low-Functioning Adults with Autism Spectrum Disorder: Distinct Sensory Profiles and Their Relationships with Behavioral Dysfunction

ERIC Educational Resources Information Center

Gonthier, Corentin; Longuépée, Lucie; Bouvard, Martine

2016-01-01

Sensory processing abnormalities are relatively universal in individuals with autism spectrum disorder, and can be very disabling. Surprisingly, very few studies have investigated these abnormalities in low-functioning adults with autism. The goals of the present study were (a) to characterize distinct profiles of sensory dysfunction, and (b) to…

Toward an operative diagnosis of fussy/picky eating: a latent profile approach in a population-based cohort

PubMed Central

2014-01-01

Background Definitions and assessment methods of fussy/picky eating are heterogeneous and remain unclear. We aimed to identify an eating behavior profile reflecting fussy/picky eating in children and to describe characteristics of fussy eaters. Methods Eating behavior was assessed with the Child Eating Behavior Questionnaire (CEBQ) in 4914 4-year olds in a population-based birth cohort study. Latent Profile Analysis (LPA) was used to identify eating behavior profiles based on CEBQ subscales. Results and discussion We found a “fussy” eating behavior profile (5.6% of children) characterized by high food fussiness, slowness in eating, and satiety responsiveness in combination with low enjoyment of food and food responsiveness. Fussy eaters were more often from families with low household income than non-fussy eaters (42% vs. 31.8% respectively; Χ 2 (1) = 9.97, p < .01). When they were 14 months old, fussy eaters had a lower intake of vegetables (t [3008] = 2.42, p < .05) and fish (t [169.77] = 2.40, p < .05) but higher intake of savory snacks (t [153.69] = -2.03, p < .05) and sweets (t [3008] = -2.30, p < .05) compared to non-fussy eaters. Also, fussy eaters were more likely to be underweight at 4 years of age (19.3%) than non-fussy eaters (12.3%; Χ 2 (1) = 7.71, p < .01). Conclusions A distinct fussy eating behavior profile was identified by LPA, which was related to family and child characteristics, food intake, and BMI. This behavior profile might be used in future research and the development of interventions. PMID:24512388

Comparative 'omics analyses differentiate Mycobacterium tuberculosis and Mycobacterium bovis and reveal distinct macrophage responses to infection with the human and bovine tubercle bacilli

PubMed Central

Malone, Kerri M.; Rue-Albrecht, Kévin; Magee, David A.; Conlon, Kevin; Schubert, Olga T.; Nalpas, Nicolas C.; Browne, John A.; Smyth, Alicia; Gormley, Eamonn; Aebersold, Ruedi; MacHugh, David E.; Gordon, Stephen V.

2018-01-01

Members of the Mycobacterium tuberculosis complex (MTBC) are the causative agents of tuberculosis in a range of mammals, including humans. A key feature of MTBC pathogens is their high degree of genetic identity yet distinct host tropism. Notably, while Mycobacterium bovis is highly virulent and pathogenic for cattle, the human pathogen M. tuberculosis is attenuated in cattle. Previous research also suggests that host preference amongst MTBC members has a basis in host innate immune responses. To explore MTBC host tropism, we present in-depth profiling of the MTBC reference strains M. bovis AF2122/97 and M. tuberculosis H37Rv at both the global transcriptional and the translational level via RNA-sequencing and SWATH MS. Furthermore, a bovine alveolar macrophage infection time course model was used to investigate the shared and divergent host transcriptomic response to infection with M. tuberculosis H37Rv or M. bovis AF2122/97. Significant differential expression of virulence-associated pathways between the two bacilli was revealed, including the ESX-1 secretion system. A divergent transcriptional response was observed between M. tuberculosis H37Rv and M. bovis AF2122/97 infection of bovine alveolar macrophages, in particular cytosolic DNA-sensing pathways at 48 h post-infection, and highlights a distinct engagement of M. bovis with the bovine innate immune system. The work presented here therefore provides a basis for the identification of host innate immune mechanisms subverted by virulent host-adapted mycobacteria to promote their survival during the early stages of infection. PMID:29557774

Systemic Analysis of Heat Shock Response Induced by Heat Shock and a Proteasome Inhibitor MG132

PubMed Central

Kim, Hee-Jung; Joo, Hye Joon; Kim, Yung Hee; Ahn, Soyeon; Chang, Jun; Hwang, Kyu-Baek; Lee, Dong-Hee; Lee, Kong-Joo

2011-01-01

The molecular basis of heat shock response (HSR), a cellular defense mechanism against various stresses, is not well understood. In this, the first comprehensive analysis of gene expression changes in response to heat shock and MG132 (a proteasome inhibitor), both of which are known to induce heat shock proteins (Hsps), we compared the responses of normal mouse fibrosarcoma cell line, RIF- 1, and its thermotolerant variant cell line, TR-RIF-1 (TR), to the two stresses. The cellular responses we examined included Hsp expressions, cell viability, total protein synthesis patterns, and accumulation of poly-ubiquitinated proteins. We also compared the mRNA expression profiles and kinetics, in the two cell lines exposed to the two stresses, using microarray analysis. In contrast to RIF-1 cells, TR cells resist heat shock caused changes in cell viability and whole-cell protein synthesis. The patterns of total cellular protein synthesis and accumulation of poly-ubiquitinated proteins in the two cell lines were distinct, depending on the stress and the cell line. Microarray analysis revealed that the gene expression pattern of TR cells was faster and more transient than that of RIF-1 cells, in response to heat shock, while both RIF-1 and TR cells showed similar kinetics of mRNA expression in response to MG132. We also found that 2,208 genes were up-regulated more than 2 fold and could sort them into three groups: 1) genes regulated by both heat shock and MG132, (e.g. chaperones); 2) those regulated only by heat shock (e.g. DNA binding proteins including histones); and 3) those regulated only by MG132 (e.g. innate immunity and defense related molecules). This study shows that heat shock and MG132 share some aspects of HSR signaling pathway, at the same time, inducing distinct stress response signaling pathways, triggered by distinct abnormal proteins. PMID:21738571

Cocaine-Induced Structural Plasticity in Input Regions to Distinct Cell Types in Nucleus Accumbens.

PubMed

Barrientos, Cindy; Knowland, Daniel; Wu, Mingche M J; Lilascharoen, Varoth; Huang, Kee Wui; Malenka, Robert C; Lim, Byung Kook

2018-05-09

The nucleus accumbens (NAc) is a brain region implicated in pathological motivated behaviors such as drug addiction and is composed predominantly of two discrete populations of neurons, dopamine receptor-1- and dopamine receptor-2-expressing medium spiny neurons (D1-MSNs and D2-MSNs, respectively). It is unclear whether these populations receive inputs from different brain areas and whether input regions to these cell types undergo distinct structural adaptations in response to the administration of addictive drugs such as cocaine. Using a modified rabies virus-mediated tracing method, we created a comprehensive brain-wide monosynaptic input map to NAc D1- and D2-MSNs. Next, we analyzed nearly 2000 dendrites and 125,000 spines of neurons across four input regions (the prelimbic cortex, medial orbitofrontal cortex, basolateral amygdala, and ventral hippocampus) at four separate time points during cocaine administration and withdrawal to examine changes in spine density in response to repeated intraperitoneal cocaine injection in mice. D1- and D2-MSNs display overall similar input profiles, with the exception that D1-MSNs receive significantly more input from the medial orbitofrontal cortex. We found that neurons in distinct brain areas projecting to D1- and D2-MSNs display different adaptations in dendritic spine density at different stages of cocaine administration and withdrawal. While NAc D1- and D2-MSNs receive input from similar brain structures, cocaine-induced spine density changes in input regions are quite distinct and dynamic. While previous studies have focused on input-specific postsynaptic changes within NAc MSNs in response to cocaine, these findings emphasize the dramatic changes that occur in the afferent input regions as well. Published by Elsevier Inc.

Melanoma patient derived xenografts acquire distinct Vemurafenib resistance mechanisms

PubMed Central

Monsma, David J; Cherba, David M; Eugster, Emily E; Dylewski, Dawna L; Davidson, Paula T; Peterson, Chelsea A; Borgman, Andrew S; Winn, Mary E; Dykema, Karl J; Webb, Craig P; MacKeigan, Jeffrey P; Duesbery, Nicholas S; Nickoloff, Brian J; Monks, Noel R

2015-01-01

Variable clinical responses, tumor heterogeneity, and drug resistance reduce long-term survival outcomes for metastatic melanoma patients. To guide and accelerate drug development, we characterized tumor responses for five melanoma patient derived xenograft models treated with Vemurafenib. Three BRAFV600E models showed acquired drug resistance, one BRAFV600E model had a complete and durable response, and a BRAFV600V model was expectedly unresponsive. In progressing tumors, a variety of resistance mechanisms to BRAF inhibition were uncovered, including mutant BRAF alternative splicing, NRAS mutation, COT (MAP3K8) overexpression, and increased mutant BRAF gene amplification and copy number. The resistance mechanisms among the patient derived xenograft models were similar to the resistance pathways identified in clinical specimens from patients progressing on BRAF inhibitor therapy. In addition, there was both inter- and intra-patient heterogeneity in resistance mechanisms, accompanied by heterogeneous pERK expression immunostaining profiles. MEK monotherapy of Vemurafenib-resistant tumors caused toxicity and acquired drug resistance. However, tumors were eradicated when Vemurafenib was combined the MEK inhibitor. The diversity of drug responses among the xenograft models; the distinct mechanisms of resistance; and the ability to overcome resistance by the addition of a MEK inhibitor provide a scheduling rationale for clinical trials of next-generation drug combinations. PMID:26101714

Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection.

PubMed

de Steenhuijsen Piters, Wouter A A; Heinonen, Santtu; Hasrat, Raiza; Bunsow, Eleonora; Smith, Bennett; Suarez-Arrabal, Maria-Carmen; Chaussabel, Damien; Cohen, Daniel M; Sanders, Elisabeth A M; Ramilo, Octavio; Bogaert, Debby; Mejias, Asuncion

2016-11-01

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity, especially among healthy children. We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem. To assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and disease severity in children less than 2 years of age with RSV infection. We characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response, and clinical disease severity. We identified five nasopharyngeal microbiota clusters characterized by enrichment of either Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus and negatively associated with S. aureus abundance, independent of age. Children with RSV showed overexpression of IFN-related genes, independent of the microbiota cluster. In addition, transcriptome profiles of children with RSV infection and H. influenzae- and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to Toll-like receptor and by neutrophil and macrophage activation and signaling. Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.

Global Genetic Response in a Cancer Cell: Self-Organized Coherent Expression Dynamics

PubMed Central

Tsuchiya, Masa; Hashimoto, Midori; Takenaka, Yoshiko; Motoike, Ikuko N.; Yoshikawa, Kenichi

2014-01-01

Understanding the basic mechanism of the spatio-temporal self-control of genome-wide gene expression engaged with the complex epigenetic molecular assembly is one of major challenges in current biological science. In this study, the genome-wide dynamical profile of gene expression was analyzed for MCF-7 breast cancer cells induced by two distinct ErbB receptor ligands: epidermal growth factor (EGF) and heregulin (HRG), which drive cell proliferation and differentiation, respectively. We focused our attention to elucidate how global genetic responses emerge and to decipher what is an underlying principle for dynamic self-control of genome-wide gene expression. The whole mRNA expression was classified into about a hundred groups according to the root mean square fluctuation (rmsf). These expression groups showed characteristic time-dependent correlations, indicating the existence of collective behaviors on the ensemble of genes with respect to mRNA expression and also to temporal changes in expression. All-or-none responses were observed for HRG and EGF (biphasic statistics) at around 10–20 min. The emergence of time-dependent collective behaviors of expression occurred through bifurcation of a coherent expression state (CES). In the ensemble of mRNA expression, the self-organized CESs reveals distinct characteristic expression domains for biphasic statistics, which exhibits notably the presence of criticality in the expression profile as a route for genomic transition. In time-dependent changes in the expression domains, the dynamics of CES reveals that the temporal development of the characteristic domains is characterized as autonomous bistable switch, which exhibits dynamic criticality (the temporal development of criticality) in the genome-wide coherent expression dynamics. It is expected that elucidation of the biophysical origin for such critical behavior sheds light on the underlying mechanism of the control of whole genome. PMID:24831017

Modeling gene-wise dependencies improves the identification of drug response biomarkers in cancer studies.

PubMed

Nikolova, Olga; Moser, Russell; Kemp, Christopher; Gönen, Mehmet; Margolin, Adam A

2017-05-01

In recent years, vast advances in biomedical technologies and comprehensive sequencing have revealed the genomic landscape of common forms of human cancer in unprecedented detail. The broad heterogeneity of the disease calls for rapid development of personalized therapies. Translating the readily available genomic data into useful knowledge that can be applied in the clinic remains a challenge. Computational methods are needed to aid these efforts by robustly analyzing genome-scale data from distinct experimental platforms for prioritization of targets and treatments. We propose a novel, biologically motivated, Bayesian multitask approach, which explicitly models gene-centric dependencies across multiple and distinct genomic platforms. We introduce a gene-wise prior and present a fully Bayesian formulation of a group factor analysis model. In supervised prediction applications, our multitask approach leverages similarities in response profiles of groups of drugs that are more likely to be related to true biological signal, which leads to more robust performance and improved generalization ability. We evaluate the performance of our method on molecularly characterized collections of cell lines profiled against two compound panels, namely the Cancer Cell Line Encyclopedia and the Cancer Therapeutics Response Portal. We demonstrate that accounting for the gene-centric dependencies enables leveraging information from multi-omic input data and improves prediction and feature selection performance. We further demonstrate the applicability of our method in an unsupervised dimensionality reduction application by inferring genes essential to tumorigenesis in the pancreatic ductal adenocarcinoma and lung adenocarcinoma patient cohorts from The Cancer Genome Atlas. : The code for this work is available at https://github.com/olganikolova/gbgfa. : nikolova@ohsu.edu or margolin@ohsu.edu. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Immunological changes in canine peripheral blood leukocytes triggered by immunization with first or second generation vaccines against canine visceral leishmaniasis.

PubMed

Araújo, Márcio Sobreira Silva; de Andrade, Renata Aline; Sathler-Avelar, Renato; Magalhães, Camila Paula; Carvalho, Andréa Teixeira; Andrade, Mariléia Chaves; Campolina, Sabrina Sidney; Mello, Maria Norma; Vianna, Leonardo Rocha; Mayrink, Wilson; Reis, Alexandre Barbosa; Malaquias, Luiz Cosme Cotta; Rocha, Luciana Morais; Martins-Filho, Olindo Assis

2011-05-15

In this study, we summarized the major phenotypic/functional aspects of circulating leukocytes following canine immunization with Leishvaccine and Leishmune®. Our findings showed that Leishvaccine triggered early changes in the innate immunity (neutrophils and eosinophils) with late alterations on monocytes. Conversely, Leishmune(®) induced early phenotypic changes in both, neutrophils and monocytes. Moreover, Leishvaccine triggered mixed activation-related phenotypic changes on T-cells (CD4+ and CD8+ and B-lymphocytes, whereas Leishmune(®) promoted a selective response, mainly associated with CD8+ T-cell activation. Mixed cytokine profile (IFN-γ/IL-4) was observed in Leishvaccine immunized dogs whereas a selective pro-inflammatory pattern (IFN-γ/NO) was induced by Leishmune® vaccination. The distinct immunological profile triggered by Leishvaccine and Leishmune® may be a direct consequence of the distinct biochemical composition of these immunobiological, i.e. complex versus purified Leishmania antigen along with Bacillus Calmette-Guérin (BCG) versus saponin adjuvant. Both immunobiologicals are able to activate phagocytes and CD8+ T-cells and therefore could be considered as a putative vaccines against canine visceral leishmaniasis (CVL). Copyright © 2011 Elsevier B.V. All rights reserved.

Screening for Homelessness in the Veterans Health Administration: Monitoring Housing Stability through Repeat Screening.

PubMed

Byrne, Thomas; Fargo, Jamison D; Montgomery, Ann Elizabeth; Roberts, Christopher B; Culhane, Dennis P; Kane, Vincent

2015-01-01

This study examined veterans' responses to the Veterans Health Administration's (VHA's) universal screen for homelessness and risk of homelessness during the first 12 months of implementation. We calculated the baseline annual frequency of homelessness and risk of homelessness among all veterans who completed an initial screen during the study period. We measured changes in housing status among veterans who initially screened positive and then completed a follow-up screen, assessed factors associated with such changes, and identified distinct risk profiles of veterans who completed a follow-up screen. More than 4 million veterans completed an initial screen; 1.8% (n=77,621) screened positive for homelessness or risk of homelessness. Of those who initially screened positive for either homelessness or risk of homelessness and who completed a second screen during the study period, 85.0% (n=15,060) resolved their housing instability prior to their second screen. Age, sex, race, VHA eligibility, and screening location were all associated with changes in housing stability. We identified four distinct risk profiles for veterans with ongoing housing instability. To address homelessness among veterans, efforts should include increased and targeted engagement of veterans experiencing persistent housing instability.

Rapid Myeloid Cell Transcriptional and Proteomic Responses to Periodontopathogenic Porphyromonas gingivalis

PubMed Central

Nares, Salvador; Moutsopoulos, Niki M.; Angelov, Nikola; Rangel, Zoila G.; Munson, Peter J.; Sinha, Neha; Wahl, Sharon M.

2009-01-01

Long-lived monocytes, macrophages, and dendritic cells (DCs) are Toll-like receptor-expressing, antigen-presenting cells derived from a common myeloid lineage that play key roles in innate and adaptive immune responses. Based on immunohistochemical and molecular analyses of inflamed tissues from patients with chronic destructive periodontal disease, these cells, found in the inflammatory infiltrate, may drive the progressive periodontal pathogenesis. To investigate early transcriptional signatures and subsequent proteomic responses to the periodontal pathogen, Porphyromonas gingivalis, donor-matched human blood monocytes, differentiated DCs, and macrophages were exposed to P. gingivalis lipopolysaccharide (LPS) and gene expression levels were measured by oligonucleotide microarrays. In addition to striking differences in constitutive transcriptional profiles between these myeloid populations, we identify a P. gingivalis LPS-inducible convergent, transcriptional core response of more than 400 annotated genes/ESTs among these populations, reflected by a shared, but quantitatively distinct, proteomic response. Nonetheless, clear differences emerged between the monocytes, DCs, and macrophages. The finding that long-lived myeloid inflammatory cells, particularly DCs, rapidly and aggressively respond to P. gingivalis LPS by generating chemokines, proteases, and cytokines capable of driving T-helper cell lineage polarization without evidence of corresponding immunosuppressive pathways highlights their prominent role in host defense and progressive tissue pathogenesis. The shared, unique, and/or complementary transcriptional and proteomic profiles may frame the context of the host response to P. gingivalis, contributing to the destructive nature of periodontal inflammation. PMID:19264901

An inducible HSP70 gene from the midge Chironomus dilutus: Characterization and transcription profile under environmental stress

USGS Publications Warehouse

Karouna-Renier, N. K.; Rao, K.R.

2009-01-01

In the present study, we identified and characterized an inducible heat shock protein 70 (HSP70) from the midge Chironomus dilutus and investigated the transcriptional profile of the gene under baseline and environmentally stressful conditions. Using real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), we observed increased expression of CD-HSP70-1 in response to both heat shock and copper stress. We also investigated the expression of this gene during midge development. All C. dilutus developmental stages expressed CD-HSP70-1 under normal conditions, although at extremely low levels. Phylogenetic analysis of the amino acid sequence demonstrated distinct clustering of this gene with inducible HSP70s from other insect species. ?? 2008 The Authors.

Odor Profile of Different Varieties of Extra-Virgin Olive Oil During Deep Frying Using an Electronic Nose and SPME-GC-FID

NASA Astrophysics Data System (ADS)

Messina, Valeria; Biolatto, Andrea; Sancho, Ana; Descalzo, Adriana; Grigioni, Gabriela; de Reca, Noemí Walsöe

2011-09-01

The aim of the performed work was to evaluate with an electronic nose changes in odor profile of Arauco and Arbequina varieties of extra-virgin olive oil during deep-frying. Changes in odor were analyzed using an electronic nose composed of 16 sensors. Volatile compounds were analyzed by SPME-GC-FID. Principal Component Analysis was applied for electronic results. Arauco variety showed the highest response for sensors. Statistical analysis for volatile compounds indicated a significant (P<0.001) interaction between variety and time of frying processes. Arauco variety showed the highest production of volatile compounds at 60 min of deep frying. The two varieties presented distinct patterns of volatile products, being clearly identified with the electronic nose.

Distinct transcriptome profiles differentiate NSAID-dependent from NSAID-independent food anaphylaxis

PubMed Central

Muñoz-Cano, Rosa; Pascal, Mariona; Bartra, Joan; Picado, Cesar; Valero, Antonio; Kim, Do-Kyun; Brooks, Stephen; Ombrello, Michael; Metcalfe, Dean D.; Rivera, Juan; Olivera, Ana

2015-01-01

Background Lipid transfer protein (LTP), an abundant protein in fruits, vegetables and nuts, is a common food allergen in Mediterranean areas causing diverse allergic reactions. Approximately 40% of food anaphylaxis induced by LTP require non-steroidal anti-inflammatory drugs (NSAIDs) as a triggering cofactor. Objective To better understand the determinants of NSAID-dependent (NSAID-LTP-A) and NSAID-independent LTP-anaphylaxis (LTP-A) Methods Selection of patients was based on a proven clinical history of NSAID-dependent or -independent anaphylaxis to LTP, positive skin prick test to LTP and serum LTP-IgE. Whole transcriptome (RNA-Seq) analysis of blood cells from 14 individuals with NSAID-LTP-A, 7 with LTP-A and 13 healthy controls was performed to identify distinct gene expression signatures. Results Expression of genes regulating gastrointestinal epithelium renewal was altered in both patient sets, particularly in LTP-A, who also presented gene expression profiles characteristic of an inflammatory syndrome. These included altered B cell pathways, increased neutrophil activation markers and elevated levels of reactive oxygen species. Increased expression of the IgG receptor (CD64) in LTP-A patients was mirrored by the presence of LTP-specific IgG1 and 3. Conversely, NSAID-LTP-A patients were characterized by reduced expression of IFN-γ-regulated genes and IFN-γ levels as well as up-regulated adenosine receptor 3 (ADORA3) expression and genes related to adenosine metabolism. Conclusions Gene ontology analysis suggests disturbances in gut epithelium homeostasis in both LTP-related anaphylaxis groups with potential integrity breaches in LTP-A that may explain their distinct inflammatory signature. Differential regulation in LTP-A and NSAID-LTP-A of the IFN-γ pathway, IgG receptors and ADORA3 may provide the pathogenic basis of their distinct responses. PMID:26194548

Genomic profiling of host responses to Lassa virus: therapeutic potential from primate to man

PubMed Central

Zapata, Juan C; Salvato, Maria S

2015-01-01

Lassa virus infection elicits distinctive changes in host gene expression and metabolism. We focus on changes in host gene expression that may be biomarkers that discriminate individual pathogens or may help to provide a prognosis for disease. In addition to assessing mRNA changes, functional studies are also needed to discriminate causes of disease from mechanisms of host resistance. Host responses that drive pathogenesis are likely to be targets for prevention or therapy. Host responses to Lassa or its related arenaviruses have been monitored in cell culture, in animal models of hemorrhagic fever, in Lassa-infected nonhuman primates and, to a limited extent, in infected human beings. Here, we describe results from those studies and discuss potential targets for reducing virus replication and mitigating disease. PMID:25844088

EXECUTIVE FUNCTION PROFILES IN CHILDREN WITH AND WITHOUT SPECIFIC LANGUAGE IMPAIRMENT

PubMed Central

Marton, Klara; Campanelli, Luca; Scheuer, Jessica; Yoon, Jungmee; Eichorn, Naomi

2013-01-01

We present findings from a study that focused on specific executive functions (EF) in children with and without specific language impairment (SLI). We analyzed performance patterns and EF profiles (spatial working memory, inhibition control, and sustained attention) in school-age SLI children and two control groups: age-matched and language matched. Our main research goal was to identify those EFs that show a weakness in children with SLI. Our specific aims were to: (1) examine whether the EF problems in children with SLI are domain-general; (2) examine whether deficits in EF in children with SLI can be explained by the general slowness hypothesis or by an overall delay in development; (3) compare EF profiles to examine whether children with SLI show a distinct pattern of performance from their peers. Our findings showed different EF profiles for the groups. We observed differences in performance patterns related to age (e.g., reaction time in response inhibition) and differences related to language status (e.g., sensitivity to interference). The findings show interesting associations in EFs that play a crucial role in language processing. PMID:25302062

Molecular phenotyping of severe asthma using pattern recognition of bronchoalveolar lavage-derived cytokines.

PubMed

Brasier, Allan R; Victor, Sundar; Boetticher, Gary; Ju, Hyunsu; Lee, Chang; Bleecker, Eugene R; Castro, Mario; Busse, William W; Calhoun, William J

2008-01-01

Asthma is a heterogeneous clinical disorder. Methods for objective identification of disease subtypes will focus on clinical interventions and help identify causative pathways. Few studies have explored phenotypes at a molecular level. We sought to discriminate asthma phenotypes on the basis of cytokine profiles in bronchoalveolar lavage (BAL) samples from patients with mild-moderate and severe asthma. Twenty-five cytokines were measured in BAL samples of 84 patients (41 severe, 43 mild-moderate) using bead-based multiplex immunoassays. The normalized data were subjected to statistical and informatics analysis. Four groups of asthmatic profiles could be identified on the basis of unsupervised analysis (hierarchical clustering) that were independent of treatment. One group, enriched in patients with severe asthma, showed differences in BAL cellular content, reductions in baseline pulmonary function, and enhanced response to methacholine provocation. Ten cytokines were identified that accurately predicted this group. Classification methods for predicting methacholine sensitivity were developed. The best model analysis predicted hyperresponders with 88% accuracy in 10 trials by using a 10-fold cross-validation. The cytokines that contributed to this model were IL-2, IL-4, and IL-5. On the basis of this classifier, 3 distinct hyperresponder classes were identified that varied in BAL eosinophil count and PC20 methacholine. Cytokine expression patterns in BAL can be used to identify distinct types of asthma and identify distinct subsets of methacholine hyperresponders. Further biomarker discovery in BAL may be informative.

Multiple network-constrained regressions expand insights into influenza vaccination responses.

PubMed

Avey, Stefan; Mohanty, Subhasis; Wilson, Jean; Zapata, Heidi; Joshi, Samit R; Siconolfi, Barbara; Tsang, Sui; Shaw, Albert C; Kleinstein, Steven H

2017-07-15

Systems immunology leverages recent technological advancements that enable broad profiling of the immune system to better understand the response to infection and vaccination, as well as the dysregulation that occurs in disease. An increasingly common approach to gain insights from these large-scale profiling experiments involves the application of statistical learning methods to predict disease states or the immune response to perturbations. However, the goal of many systems studies is not to maximize accuracy, but rather to gain biological insights. The predictors identified using current approaches can be biologically uninterpretable or present only one of many equally predictive models, leading to a narrow understanding of the underlying biology. Here we show that incorporating prior biological knowledge within a logistic modeling framework by using network-level constraints on transcriptional profiling data significantly improves interpretability. Moreover, incorporating different types of biological knowledge produces models that highlight distinct aspects of the underlying biology, while maintaining predictive accuracy. We propose a new framework, Logistic Multiple Network-constrained Regression (LogMiNeR), and apply it to understand the mechanisms underlying differential responses to influenza vaccination. Although standard logistic regression approaches were predictive, they were minimally interpretable. Incorporating prior knowledge using LogMiNeR led to models that were equally predictive yet highly interpretable. In this context, B cell-specific genes and mTOR signaling were associated with an effective vaccination response in young adults. Overall, our results demonstrate a new paradigm for analyzing high-dimensional immune profiling data in which multiple networks encoding prior knowledge are incorporated to improve model interpretability. The R source code described in this article is publicly available at https://bitbucket.org/kleinstein/logminer . steven.kleinstein@yale.edu or stefan.avey@yale.edu. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Use of mutation profiles to refine the classification of endometrial carcinomas

PubMed Central

Cheang, Maggie CU; Wiegand, Kimberly; Senz, Janine; Tone, Alicia; Yang, Winnie; Prentice, Leah; Tse, Kane; Zeng, Thomas; McDonald, Helen; Schmidt, Amy P.; Mutch, David G.; McAlpine, Jessica N; Hirst, Martin; Shah, Sohrab P; Lee, Cheng-Han; Goodfellow, Paul J; Gilks, C. Blake; Huntsman, David G

2014-01-01

The classification of endometrial carcinomas is based on pathological assessment of tumour cell type; the different cell types (endometrioid, serous, carcinosarcoma, mixed, and clear cell) are associated with distinct molecular alterations. This current classification system for high-grade subtypes, in particular the distinction between high-grade endometrioid (EEC-3) and serous carcinomas (ESC), is limited in its reproducibility and prognostic abilities. Therefore, a search for specific molecular classifiers to improve endometrial carcinoma subclassification is warranted. We performed target enrichment sequencing on 393 endometrial carcinomas from two large cohorts, sequencing exons from the following 9 genes; ARID1A, PPP2R1A, PTEN, PIK3CA, KRAS, CTNNB1, TP53, BRAF and PPP2R5C. Based on this gene panel each endometrial carcinoma subtype shows a distinct mutation profile. EEC-3s have significantly different frequencies of PTEN and TP53 mutations when compared to low-grade endometrioid carcinomas. ESCs and EEC-3s are distinct subtypes with significantly different frequencies of mutations in PTEN, ARID1A, PPP2R1A, TP53, and CTNNB1. From the mutation profiles we were able to identify subtype outliers, i.e. cases diagnosed morphologically as one subtype but with a mutation profile suggestive of a different subtype. Careful review of these diagnostically challenging cases suggested that the original morphological classification was incorrect in most instances. The molecular profile of carcinosarcomas suggests two distinct mutation profiles for these tumours; endometrioid-type (PTEN, PIK3CA, ARID1A, KRAS mutations), and serous-type (TP53 and PPP2R1A mutations). While this nine gene panel does not allow for a purely molecularly based classification of endometrial carcinoma, it may prove useful as an adjunct to morphological classification and serve as an aid in the classification of problematic cases. If used in practice, it may lead to improved diagnostic reproducibility and may also serve to stratify patients for targeted therapeutics. PMID:22653804

The Different Facets of Work Stress: A Latent Profile Analysis of Nurses' Work Demands.

PubMed

Jenull, Brigitte B; Wiedermann, Wolfgang

2015-10-01

Work-related stress has been identified as a relevant problem leading to negative effects on health and quality of life. Using data from 844 nurses, latent profile analyses (LPA) were applied to identify distinct patterns of work stress. Several sociodemographic variables, including nurses' working and living conditions, as well as nurses' reactions to workload, were considered to predict respondents' profile membership. LPA revealed three distinct profiles that can be distinguished by a low, moderate, and higher stress level. Being financially secure is positively related to the low stress profile, whereas working in an urban area and having low job satisfaction increases the chance of belonging to the higher stress profile. Our results can be used as a basis to develop interventions to create a healthy nursing home environment by supporting the balance between family and work, providing access to job resources and optimizing recovery opportunities. © The Author(s) 2013.

Distinct developmental profiles in typical speech acquisition

PubMed Central

Campbell, Thomas F.; Shriberg, Lawrence D.; Green, Jordan R.; Abdi, Hervé; Rusiewicz, Heather Leavy; Venkatesh, Lakshmi; Moore, Christopher A.

2012-01-01

Three- to five-year-old children produce speech that is characterized by a high level of variability within and across individuals. This variability, which is manifest in speech movements, acoustics, and overt behaviors, can be input to subgroup discovery methods to identify cohesive subgroups of speakers or to reveal distinct developmental pathways or profiles. This investigation characterized three distinct groups of typically developing children and provided normative benchmarks for speech development. These speech development profiles, identified among 63 typically developing preschool-aged speakers (ages 36–59 mo), were derived from the children's performance on multiple measures. These profiles were obtained by submitting to a k-means cluster analysis of 72 measures that composed three levels of speech analysis: behavioral (e.g., task accuracy, percentage of consonants correct), acoustic (e.g., syllable duration, syllable stress), and kinematic (e.g., variability of movements of the upper lip, lower lip, and jaw). Two of the discovered group profiles were distinguished by measures of variability but not by phonemic accuracy; the third group of children was characterized by their relatively low phonemic accuracy but not by an increase in measures of variability. Analyses revealed that of the original 72 measures, 8 key measures were sufficient to best distinguish the 3 profile groups. PMID:22357794

Identifying seasonal mobility profiles from anonymized and aggregated mobile phone data. Application in food security.

PubMed

Zufiria, Pedro J; Pastor-Escuredo, David; Úbeda-Medina, Luis; Hernandez-Medina, Miguel A; Barriales-Valbuena, Iker; Morales, Alfredo J; Jacques, Damien C; Nkwambi, Wilfred; Diop, M Bamba; Quinn, John; Hidalgo-Sanchís, Paula; Luengo-Oroz, Miguel

2018-01-01

We propose a framework for the systematic analysis of mobile phone data to identify relevant mobility profiles in a population. The proposed framework allows finding distinct human mobility profiles based on the digital trace of mobile phone users characterized by a Matrix of Individual Trajectories (IT-Matrix). This matrix gathers a consistent and regularized description of individual trajectories that enables multi-scale representations along time and space, which can be used to extract aggregated indicators such as a dynamic multi-scale population count. Unsupervised clustering of individual trajectories generates mobility profiles (clusters of similar individual trajectories) which characterize relevant group behaviors preserving optimal aggregation levels for detailed and privacy-secured mobility characterization. The application of the proposed framework is illustrated by analyzing fully anonymized data on human mobility from mobile phones in Senegal at the arrondissement level over a calendar year. The analysis of monthly mobility patterns at the livelihood zone resolution resulted in the discovery and characterization of seasonal mobility profiles related with economic activities, agricultural calendars and rainfalls. The use of these mobility profiles could support the timely identification of mobility changes in vulnerable populations in response to external shocks (such as natural disasters, civil conflicts or sudden increases of food prices) to monitor food security.

Prefrontal mediation of the reading network predicts intervention response in dyslexia.

PubMed

Aboud, Katherine S; Barquero, Laura A; Cutting, Laurie E

2018-04-01

A primary challenge facing the development of interventions for dyslexia is identifying effective predictors of intervention response. While behavioral literature has identified core cognitive characteristics of response, the distinction of reading versus executive cognitive contributions to response profiles remains unclear, due in part to the difficulty of segregating these constructs using behavioral outputs. In the current study we used functional neuroimaging to piece apart the mechanisms of how/whether executive and reading network relationships are predictive of intervention response. We found that readers who are responsive to intervention have more typical pre-intervention functional interactions between executive and reading systems compared to nonresponsive readers. These findings suggest that intervention response in dyslexia is influenced not only by domain-specific reading regions, but also by contributions from intervening domain-general networks. Our results make a significant gain in identifying predictive bio-markers of outcomes in dyslexia, and have important implications for the development of personalized clinical interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of atmospheric carbon dioxide levels and nitrate fertilization on glucosinolate biosynthesis in mechanically damaged Arabidopsis plants.

PubMed

Paudel, Jamuna Risal; Amirizian, Alexandre; Krosse, Sebastian; Giddings, Jessica; Ismail, Shoieb Akaram Arief; Xia, Jianguo; Gloer, James B; van Dam, Nicole M; Bede, Jacqueline C

2016-03-22

Increased atmospheric carbon dioxide (CO2) levels predicted to occur before the end of the century will impact plant metabolism. In addition, nitrate availability will affect metabolism and levels of nitrogen-containing defense compounds, such as glucosinolates (GSLs). We compared Arabidopsis foliar metabolic profile in plants grown under two CO2 regimes (440 vs 880 ppm), nitrate fertilization (1 mM vs 10 mM) and in response to mechanical damage of rosette leaves. Constitutive foliar metabolites in nitrate-limited plants show distinct global patterns depending on atmospheric CO2 levels; in contrast, plants grown under higher nitrate fertilization under elevated atmospheric CO2 conditions have a unique metabolite signature. Nitrate fertilization dampens the jasmonate burst in response to wounding in plants grown at elevated CO2 levels. Leaf GSL profile mirrors the jasmonate burst; in particular, indole GSLs increase in response to damage in plants grown at ambient CO2 but only in nitrate-limited plants grown under elevated CO2 conditions. This may reflect a reduced capacity of C3 plants grown under enriched CO2 and nitrate levels to signal changes in oxidative stress and has implications for future agricultural management practices.

Subsurface damage in precision ground ULE(R) and Zerodur(R) surfaces.

PubMed

Tonnellier, X; Morantz, P; Shore, P; Baldwin, A; Evans, R; Walker, D D

2007-09-17

The total process cycle time for large ULE((R)) and Zerodur((R))optics can be improved using a precise and rapid grinding process, with low levels of surface waviness and subsurface damage. In this paper, the amounts of defects beneath ULE((R)) and Zerodur((R) )surfaces ground using a selected grinding mode were compared. The grinding response was characterised by measuring: surface roughness, surface profile and subsurface damage. The observed subsurface damage can be separated into two distinct depth zones, which are: 'process' and 'machine dynamics' related.

PROSPECT: Profiling of Resistance Patterns & Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax and Therapeutic Target Identification

DTIC Science & Technology

2012-06-01

neoadjuvant therapies on disease-free, progression-free, and overall survival will vary across prognostically distinct groups. 3. Specific molecular... prognostically distinct subpopulations of patients with resectable NSCLC, and to assess the extent to which these molecular profiles correlate with tumor...overall survival, and will use Cox proportional hazards models and recursive partitioning methods to identify important biomarkers and prognostically

Probes of Ubiquitin E3 ligases distinguish different stages of Parkin activation

PubMed Central

Pao, Kuan-Chuan; Stanley, Mathew; Han, Cong; Lai, Yu-Chiang; Murphy, Paul; Balk, Kristin; Wood, Nicola T.; Corti, Olga; Corvol, Jean-Christophe; Muqit, Miratul M.K.; Virdee, Satpal

2016-01-01

E3 ligases represent an important class of enzymes, yet there are currently no chemical probes to profile their activity. We develop a new class of activity-based probe by reengineering of a ubiquitin-charged E2 conjugating enzyme and demonstrate their utility by profiling the transthiolation activity of the RING-in-between-RING (RBR) E3 ligase Parkin in vitro and in cellular extracts. Our study provides valuable insight into the roles, and cellular hierarchy, of distinct phosphorylation events in Parkin activation. We also profile Parkin patient disease-associated mutations and strikingly demonstrate that they largely mediate their effect by altering transthiolation activity. Furthermore, our probes enable direct and quantitative measurement of endogenous Parkin activity revealing that endogenous Parkin is activated in neuronal cell lines (≥75 %) in response to mitochondrial depolarization. This new technology also holds promise as a novel biomarker of PINK1-Parkin signalling as demonstrated by compatibility with Parkinson’s disease patient-derived samples. PMID:26928937

[Toxin profiles in fish implicated in ciguatera fish poisoning in Amami and Kakeroma Islands, Kagoshima Prefecture, Japan].

PubMed

Yogi, Kentaro; Oshiro, Naomasa; Matsuda, Seiko; Sakugawa, Satsuki; Matsuo, Toshiaki; Yasumoto, Takeshi

2013-01-01

Ciguatoxins (CTXs) responsible for ciguatera fish poisoning (CFP) in Amami Islands, Kagoshima, Japan in 2008 were determined by LC-MS/MS analysis. Ciguatoxin-1B (CTX1B), 54-deoxyCTX1B, and 52-epi-54-deoxyCTX1B were detected in Variola louti and Lutjanus monostigma. The toxin profile distinctly differed from that of a CFP-related fish from Miyazaki, which mainly contained ciguatoxin-3C type toxins. Toxin profiles were species-specific, as observed in fish from Okinawa. The LC-MS/MS and mouse bioassay (MBA) methods produced comparable data, though 54-deoxyCTX1B was not taken into consideration owing to the lack of toxicity data. To improve assessment, toxicity data for this compound are needed. A reef fish caught on the same occasion and judged nontoxic by MBA (<0.025 MU/g) was found to contain low levels of CTX, indicating a potential risk for CFP.

Dynamics of Vegetatin Indices in Tropical and Subtropical Savannas Defined by Ecoregions and Moderate Resolution Imaging Spectoradiometer (MODIS) Land Cover

NASA Technical Reports Server (NTRS)

Hill, Michael J.; Roman, Miguel O.; Schaaf, Crytal B.

2011-01-01

In this study, we explored the capacity of vegetation indices derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) reflectance products to characterize global savannas in Australia, Africa and South America. The savannas were spatially defined and subdivided using the World Wildlife Fund (WWF) global ecoregions and MODIS land cover classes. Average annual profiles of Normalized Difference Vegetation Index, shortwave infrared ratio (SWIR32), White Sky Albedo (WSA) and the Structural Scattering Index (SSI) were created. Metrics derived from average annual profiles of vegetation indices were used to classify savanna ecoregions. The response spaces between vegetation indices were used to examine the potential to derive structural and fractional cover measures. The ecoregions showed distinct temporal profiles and formed groups with similar structural properties, including higher levels of woody vegetation, similar forest savanna mixtures and similar grassland predominance. The potential benefits from the use of combinations of indices to characterize savannas are discussed.

Ripening and storage conditions of Chétoui and Arbequina olives: Part I. Effect on olive oils volatiles profile.

PubMed

Hachicha Hbaieb, Rim; Kotti, Faten; Gargouri, Mohamed; Msallem, Monji; Vichi, Stefania

2016-07-15

The distinctive aroma of virgin olive oil is mainly attributed to its volatile profile including components responsible for positive attributes and others for sensory defects resulting from chemical oxidation and exogenous enzymes. For this reason, the evolution of volatile compounds from Chétoui and Arbequina virgin olive oils during olive ripening and storage (at 4 and 25 °C during 4 weeks) was investigated. The profile of volatile phenols during olive storage was also studied. Quantitative differences in the volatile compounds during olive storage at 4 and 25 °C according to olive cultivar was determined. Concerning the volatile phenols, the Arbequina olives were the most affected by high storage temperature, as the formation of these compounds, especially 4-ethyl and 4-vinyl derivatives of phenol and guaiacol were more noticeable in Arbequina oils extracted from stored fruits at 25 °C. Copyright © 2016 Elsevier Ltd. All rights reserved.

Physiological Profiles During Delay of Gratification: Associations with Emotionality, Self-regulation, and Adjustment Problems

PubMed Central

Wilson, Anna C.; Lengua, Liliana J.; Tininenko, Jennifer; Taylor, Adam; Trancik, Anika

2009-01-01

This longitudinal study utilized a community sample of children (N=91, 45% female, 8–11 years at time 1) to investigate physiological responses (heart rate reactivity [HRR] and electrodermal responding [EDR]) during delay of gratification in relation to emotionality, self-regulation, and adjustment problems. Cluster analyses identified three profiles among children who successfully delayed: children who waited easily with low EDR and moderate HRR, children who had difficulty waiting with high EDR and moderate HRR, and children who had difficulty waiting with low EDR and low HRR. The 3 clusters and children who did not wait were compared. Children with low EDR-low HRR had the lowest self-regulation, and like the no-wait group, demonstrated the greatest baseline adjustment problems. The high EDR-moderate HRR group demonstrated highest self-regulation and increases in depression across one year. Distinct profiles among children in delay contexts point to children who are over- and under-regulated with implications for adjustment problems. PMID:20046898

Adjudicating between face-coding models with individual-face fMRI responses

PubMed Central

Kriegeskorte, Nikolaus

2017-01-01

The perceptual representation of individual faces is often explained with reference to a norm-based face space. In such spaces, individuals are encoded as vectors where identity is primarily conveyed by direction and distinctiveness by eccentricity. Here we measured human fMRI responses and psychophysical similarity judgments of individual face exemplars, which were generated as realistic 3D animations using a computer-graphics model. We developed and evaluated multiple neurobiologically plausible computational models, each of which predicts a representational distance matrix and a regional-mean activation profile for 24 face stimuli. In the fusiform face area, a face-space coding model with sigmoidal ramp tuning provided a better account of the data than one based on exemplar tuning. However, an image-processing model with weighted banks of Gabor filters performed similarly. Accounting for the data required the inclusion of a measurement-level population averaging mechanism that approximates how fMRI voxels locally average distinct neuronal tunings. Our study demonstrates the importance of comparing multiple models and of modeling the measurement process in computational neuroimaging. PMID:28746335

Gene expression profiles associated with anaemia and ITPA genotypes in patients with chronic hepatitis C (CH-C).

PubMed

Birerdinc, A; Estep, M; Afendy, A; Stepanova, M; Younossi, I; Baranova, A; Younossi, Z M

2012-06-01

Anaemia is a common side effect of ribavirin (RBV) which is used for the treatment of hepatitis C. Inosine triphosphatase gene polymorphism (C to A) protects against RBV-induced anaemia. The aim of our study was to genotype patients for inosine triphosphatase gene polymorphism rs1127354 SNP (CC or CA) and associate treatment-induced anaemia with gene expression profile and genotypes. We used 67 hepatitis C patients with available gene expression, clinical, laboratory data and whole-blood samples. Whole blood was used to determine inosine triphosphatase gene polymorphism rs1127354 genotypes (CC or CA). The cohort with inosine triphosphatase gene polymorphism CA genotype revealed a distinct pattern of protection against anaemia and a lower drop in haemoglobin. A variation in the propensity of CC carriers to develop anaemia prompted us to look for additional predictors of anaemia during pegylated interferon (PEG-IFN) and RBV. Pretreatment blood samples of patients receiving a full course of PEG-IFN and RBV were used to assess expression of 153 genes previously implicated in host response to viral infections. The gene expression data were analysed according to presence of anaemia and inosine triphosphatase gene polymorphism genotypes. Thirty-six genes were associated with treatment-related anaemia, six of which are involved in the response to hypoxia pathway (HIF1A, AIF1, RHOC, PTEN, LCK and PDGFB). There was a substantial overlap between sustained virological response (SVR)-predicting and anaemia-related genes; however, of the nine JAK-STAT pathway-related genes associated with SVR, none were implicated in anaemia. These observations exclude the direct involvement of antiviral response in the development of anaemia associated with PEG-IFN and RBV treatment, whereas another, distinct component within the SVR-associated gene expression response may predict anaemia. We have identified baseline gene expression signatures associated with RBV-induced anaemia and identified its functional pathways. In particular, we identified the hypoxia response pathway and the apoptosis/survival-related gene network, as differentially expressed in chronic hepatitis C patients with anaemia. © 2011 Blackwell Publishing Ltd.

Modulation of Androgen Receptor Signaling in Hormonal Therapy-Resistant Prostate Cancer Cell Lines

PubMed Central

Marques, Rute B.; Dits, Natasja F.; Erkens-Schulze, Sigrun; van IJcken, Wilfred F. J.; van Weerden, Wytske M.; Jenster, Guido

2011-01-01

Background Prostate epithelial cells depend on androgens for survival and function. In (early) prostate cancer (PCa) androgens also regulate tumor growth, which is exploited by hormonal therapies in metastatic disease. The aim of the present study was to characterize the androgen receptor (AR) response in hormonal therapy-resistant PC346 cells and identify potential disease markers. Methodology/Principal Findings Human 19K oligoarrays were used to establish the androgen-regulated expression profile of androgen-responsive PC346C cells and its derivative therapy-resistant sublines: PC346DCC (vestigial AR levels), PC346Flu1 (AR overexpression) and PC346Flu2 (T877A AR mutation). In total, 107 transcripts were differentially-expressed in PC346C and derivatives after R1881 or hydroxyflutamide stimulations. The AR-regulated expression profiles reflected the AR modifications of respective therapy-resistant sublines: AR overexpression resulted in stronger and broader transcriptional response to R1881 stimulation, AR down-regulation correlated with deficient response of AR-target genes and the T877A mutation resulted in transcriptional response to both R1881 and hydroxyflutamide. This AR-target signature was linked to multiple publicly available cell line and tumor derived PCa databases, revealing that distinct functional clusters were differentially modulated during PCa progression. Differentiation and secretory functions were up-regulated in primary PCa but repressed in metastasis, whereas proliferation, cytoskeletal remodeling and adhesion were overexpressed in metastasis. Finally, the androgen-regulated genes ENDOD1, MCCC2 and ACSL3 were selected as potential disease markers for RT-PCR quantification in a distinct set of human prostate specimens. ENDOD1 and ACSL3 showed down-regulation in high-grade and metastatic PCa, while MCCC2 was overexpressed in low-grade PCa. Conclusions/Significance AR modifications altered the transcriptional response to (anti)androgens in therapy-resistant cells. Furthermore, selective down-regulation of genes involved in differentiation and up-regulation of genes promoting proliferation and invasion suggest a disturbed balance between the growth and differentiation functions of the AR pathway during PCa progression. These findings may have implications in the current treatment and development of novel therapeutical approaches for metastatic PCa. PMID:21829708

Differentiating asthma phenotypes in young adults through polyclonal cytokine profiles.

PubMed

Zoratti, Edward; Havstad, Suzanne; Wegienka, Ganesa; Nicholas, Charlotte; Bobbitt, Kevin R; Woodcroft, Kimberley J; Ownby, Dennis R; Johnson, Christine Cole

2014-07-01

Recent research has emphasized the need to better discriminate asthma phenotypes and consider underlying mechanistic endotypes in epidemiologic and clinical studies. Although allergic asthma and nonallergic asthma are frequently combined into 1 disease category in observational research and clinical trials, few studies have investigated the extent to which these 2 separate phenotypes are associated with distinct cytokine immunologic profiles in a representative young adult population. To investigate the cytokine production-based endotypes underlying the clinical phenotypes of allergic and nonallergic asthma in a population-based birth cohort evaluated as young adults. Participants included 18- to 21-year-old members (n = 540) of a suburban Detroit birth cohort study, the Childhood Allergy Study. Phorbol myristate acetate-stimulated whole blood interleukin (IL)-4, IL-5, IL-10, IL-12, IL-13, IL-17A, IL-17F, IL-22, and interferon-γ secretory responses were analyzed for associations comparing participants with allergic vs nonallergic asthma phenotypes with those without asthma. T-helper cell type (TH) 2-polarized responses, measured as higher mean IL-5 and IL-13 secretions and lower ratios of interferon-γ and IL-12 to 3 TH2 cytokines (IL-4, IL-5, or IL-13), were observed only in participants with allergic asthma. Nonallergic asthma was associated with TH1-polarized responses, including higher adjusted interferon-γ secretion compared with participants with allergic asthma and, surprisingly, those without asthma (odds ratio 2.5, confidence interval 1.2-5.1, P < .01). As expected, young adults with a history of an allergic asthma phenotype exhibited a TH2-polarized cytokine response after polyclonal stimulation. However, TH1 polarization was observed in patients with a history of nonallergic asthma. Allergic and nonallergic asthma are associated with etiologically distinct immune endotypes, underscoring the importance of discriminating these endotypes in research analyses and clinical management. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Fabrication and characterization of anisotropic nanofiber scaffolds for advanced drug delivery systems

PubMed Central

Jalani, Ghulam; Jung, Chan Woo; Lee, Jae Sang; Lim, Dong Woo

2014-01-01

Stimuli-responsive, polymer-based nanostructures with anisotropic compartments are of great interest as advanced materials because they are capable of switching their shape via environmentally-triggered conformational changes, while maintaining discrete compartments. In this study, a new class of stimuli-responsive, anisotropic nanofiber scaffolds with physically and chemically distinct compartments was prepared via electrohydrodynamic cojetting with side-by-side needle geometry. These nanofibers have a thermally responsive, physically-crosslinked compartment, and a chemically-crosslinked compartment at the nanoscale. The thermally responsive compartment is composed of physically crosslinkable poly(N-isopropylacrylamide) poly(NIPAM) copolymers, and poly(NIPAM-co-stearyl acrylate) poly(NIPAM-co-SA), while the thermally-unresponsive compartment is composed of polyethylene glycol dimethacrylates. The two distinct compartments were physically crosslinked by the hydrophobic interaction of the stearyl chains of poly(NIPAM-co-SA) or chemically stabilized via ultraviolet irradiation, and were swollen in physiologically relevant buffers due to their hydrophilic polymer networks. Bicompartmental nanofibers with the physically-crosslinked network of the poly(NIPAM-co-SA) compartment showed a thermally-triggered shape change due to thermally-induced aggregation of poly(NIPAM-co-SA). Furthermore, when bovine serum albumin and dexamethasone phosphate were separately loaded into each compartment, the bicompartmental nanofibers with anisotropic actuation exhibited decoupled, controlled release profiles of both drugs in response to a temperature. A new class of multicompartmental nanofibers could be useful for advanced nanofiber scaffolds with two or more drugs released with different kinetics in response to environmental stimuli. PMID:24872702

Enhancing field GP engagement in hospital-based studies. Rationale, design, main results and participation in the Diagest 3-GP motivation study.

PubMed

Berkhout, Christophe; Vandaele-Bétancourt, Marie; Robert, Stéphane; Lespinasse, Solène; Mitha, Gamil; Bradier, Quentin; Vambergue, Anne; Fontaine, Pierre

2012-06-21

Diagest 3 was a study aimed at lowering the risk of developing type 2 diabetes within 3 years after childbirth. Women with gestational diabetes were enrolled in the study. After childbirth, the subjects showed little interest in the structured education programme and did not attend workshops. Their general practitioners (GPs) were approached to help motivate the subjects to participate in Diagest 3, but the GPs were reluctant. The present study aimed to understand field GPs' attitudes towards hospital-based studies, and to develop strategies to enhance their involvement and reduce subject drop-out rates. We used a three-step process: step one used a phenomenological approach exploring the beliefs, attitudes, motivations and environmental factors contributing to the GPs' level of interest in the study. Data were collected in face-to-face interviews and coded by hand and with hermeneutic software to develop distinct GP profiles. Step two was a cross-sectional survey by questionnaire to determine the distribution of the profiles in the GP study population and whether completion of an attached case report form (CRF) was associated with a particular GP profile. In step three, we assessed the impact of the motivation study on participation rates in the main study. Fifteen interviews were conducted to achieve data saturation. Theorisation led to the definition of 4 distinct GP profiles. The response rate to the questionnaire was 73%, but dropped to 52% when a CRF was attached. The link between GP profiles and the rate of CRF completion remains to be verified. The GPs provided data on the CRF that was of comparable quality to those collected in the main trial. Our analysis showed that the motivation study increased overall participation in the main study by 23%, accounting for 16% (24/152) of all final visits for 536 patients who were initially enrolled in the Diagest 3 study. When a hospital-led study explores issues in primary care, its design must anticipate GP participation early in the trial. Based on our questionnaire response rates, we found that one in two GPs were willing to participate in our hospital-led study, regardless of their initial attitudes.

Investigating the Neural Basis of Theta Burst Stimulation to Premotor Cortex on Emotional Vocalization Perception: A Combined TMS-fMRI Study

PubMed Central

Agnew, Zarinah K.; Banissy, Michael J.; McGettigan, Carolyn; Walsh, Vincent; Scott, Sophie K.

2018-01-01

Previous studies have established a role for premotor cortex in the processing of auditory emotional vocalizations. Inhibitory continuous theta burst transcranial magnetic stimulation (cTBS) applied to right premotor cortex selectively increases the reaction time to a same-different task, implying a causal role for right ventral premotor cortex (PMv) in the processing of emotional sounds. However, little is known about the functional networks to which PMv contribute across the cortical hemispheres. In light of these data, the present study aimed to investigate how and where in the brain cTBS affects activity during the processing of auditory emotional vocalizations. Using functional neuroimaging, we report that inhibitory cTBS applied to the right premotor cortex (compared to vertex control site) results in three distinct response profiles: following stimulation of PMv, widespread frontoparietal cortices, including a site close to the target site, and parahippocampal gyrus displayed an increase in activity, whereas the reverse response profile was apparent in a set of midline structures and right IFG. A third response profile was seen in left supramarginal gyrus in which activity was greater post-stimulation at both stimulation sites. Finally, whilst previous studies have shown a condition specific behavioral effect following cTBS to premotor cortex, we did not find a condition specific neural change in BOLD response. These data demonstrate a complex relationship between cTBS and activity in widespread neural networks and are discussed in relation to both emotional processing and the neural basis of cTBS. PMID:29867402

Heterogeneity in the pharmacodynamics of two long-acting methylphenidate formulations for children with attention deficit/hyperactivity disorder. A growth mixture modelling analysis.

PubMed

Sonuga-Barke, Edmund J S; Van Lier, Pol; Swanson, James M; Coghill, David; Wigal, Sharon; Vandenberghe, Mieke; Hatch, Simon

2008-06-01

To use growth mixture modelling (GMM) to identify subgroups of children with attention deficit hyperactive disorder (ADHD) who have different pharmacodynamic profiles in response to extended release methylphenidate as assessed in a laboratory classroom setting. GMM analysis was performed on data from the COMACS study (Comparison of Methylphenidates in the Analog Classroom Setting): a large (n = 184) placebo-controlled cross-over study comparing three treatment conditions in the Laboratory School Protocol (with a 1.5-h cycle of attention and deportment assessments). Two orally administered, once-daily methylphenidate (MPH) bioequivalent formulations [Metadate CD/Equasym XL (MCD-EQXL) and Concerta XL (CON)] were compared with placebo (PLA). Three classes of children with distinct severity profiles in the PLA condition were identified. For both MCD-EQXL and CON, the more severe their PLA symptoms the better, the children's response. However, the formulations produced different growth curves by class, with CON having essentially a flat profile for all three classes (i.e. no effect of PLA severity) and MCD-EQXL showing a marked decline in symptoms immediately post-dosing in the two most severe classes compared with the least severe. Comparison of daily doses matched for immediate-release (IR) components accounted for this difference. The results suggest considerable heterogeneity in the pharmacodynamics of MPH response by children with ADHD. When treatment response for near-equal, bioequivalent daily doses the two formulations was compared, marked differences were seen for children in the most severe classes with a strong curvilinear trajectory for MCD-EQXL related to the greater IR component.

Androgen responses to reproductive competition of males pursuing either fixed or plastic alternative reproductive tactics.

PubMed

von Kuerthy, Corinna; Ros, Albert F H; Taborsky, Michael

2016-11-15

Alternative reproductive tactics (ARTs), which can be plastic or fixed for life, may be characterized by distinct hormonal profiles. The relative plasticity hypothesis predicts flexible androgen regulation for adult males pursuing plastic tactics, but a less flexible regulation for males using a fixed tactic throughout life. Furthermore, androgen profiles may respond to changes in the social environment, as predicted by the social reciprocity models of hormone/behaviour interactions. The cichlid fish Lamprologus callipterus provides a rare opportunity to study the roles of androgens for male ARTs within a single species, because fixed and plastic ARTs coexist. We experimentally exposed males to competitors pursuing either the same or different tactics to test predictions of the relative plasticity and the social reciprocity models. Androgen profiles of different male types partly comply with predictions derived from the relative plasticity hypothesis: males of the plastic bourgeois/sneaker male trajectory showed different 11-ketotestosterone (11-KT) levels when pursuing either bourgeois or parasitic sneaker male behaviours. Surprisingly, males pursuing the fixed dwarf male tactic showed the highest free and conjugated 11-KT and testosterone (T) levels. Our experimental social challenges significantly affected the free 11-KT levels of bourgeois males, but the androgen responses did not differ between challenges involving different types of competitors. Furthermore, the free T-responses of the bourgeois males correlated with their aggressive behaviour exhibited against competitors. Our results provide new insights into the endocrine responsiveness of fixed and plastic ARTs, confirming and refuting some predictions of both the relative plasticity and the social reciprocity models. © 2016. Published by The Company of Biologists Ltd.

Quantitative sensory testing somatosensory profiles in patients with cervical radiculopathy are distinct from those in patients with nonspecific neck-arm pain.

PubMed

Tampin, Brigitte; Slater, Helen; Hall, Toby; Lee, Gabriel; Briffa, Noelle Kathryn

2012-12-01

The aim of this study was to establish the somatosensory profiles of patients with cervical radiculopathy and patients with nonspecific neck-arm pain associated with heightened nerve mechanosensitivity (NSNAP). Sensory profiles were compared to healthy control (HC) subjects and a positive control group comprising patients with fibromyalgia (FM). Quantitative sensory testing (QST) of thermal and mechanical detection and pain thresholds, pain sensitivity and responsiveness to repetitive noxious mechanical stimulation was performed in the maximal pain area, the corresponding dermatome and foot of 23 patients with painful C6 or C7 cervical radiculopathy, 8 patients with NSNAP in a C6/7 dermatomal pain distribution, 31 HC and 22 patients with FM. For both neck-arm pain groups, all QST parameters were within the 95% confidence interval of HC data. Patients with cervical radiculopathy were characterised by localised loss of function (thermal, mechanical, vibration detection P<.009) in the maximal pain area and dermatome (thermal detection, vibration detection, pressure pain sensitivity P<.04), consistent with peripheral neuronal damage. Both neck-arm pain groups demonstrated increased cold sensitivity in their maximal pain area (P<.03) and the foot (P<.009), and this was also the dominant sensory characteristic in patients with NSNAP. Both neck-arm pain groups differed from patients with FM, the latter characterised by a widespread gain of function in most nociceptive parameters (thermal, pressure, mechanical pain sensitivity P<.027). Despite commonalities in pain characteristics between the 2 neck-arm pain groups, distinct sensory profiles were demonstrated for each group. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Immune response of patients with recurrent aphthous stomatitis challenged with a symbiotic.

PubMed

Mimura, Maria Angela Martins; Borra, Ricardo Carneiro; Hirata, Cleonice Hitomi Watashi; de Oliveira Penido, Norma

2017-10-01

There are indications that Th1 polarization of immune response plays an important role in the pathogenesis of recurrent aphthous stomatitis (RAS), and that the use of probiotics can stimulate immune regulatory activity, influencing the course of the disease. The aim of this study was to characterize the initial immune profile of RAS patients and evaluate clinical and serological response following a challenge with symbiotic treatment containing fructooligosaccharide, Lactobacillus, and Bifidobacterium. The immune responses of the 45 patients with RAS, submitted to symbiotic or placebo for 120 days, in relation to 30 RAS-free controls, were evaluated over a period of 6 months. Peripheral blood was collected from all patients at 0 (T0), 120 (T4), and 180 days (T6) after the start of treatment and Th1 (IL12-p70, IFN-γ), Th2 (IL-4), Treg (IL-10), Th17 (IL-17A), inflammatory (TNF-α, IL-6)-associated cytokines, and clinical parameters were quantified. At T0, significant differences were found in the serological levels of the IFN-γ, IL-4, and IL-6 cytokines of the RAS patients in comparison with the controls. It was observed that the cytokine profile of the RAS group was comprised of 2 distinct clusters: a pure Th2 and a Mixed (Th1/Th2) subtype and that symbiotic treatment induced an improvement in pain and an increase in IFN-γ levels, producing a reduction in Th2 response. In RAS, symbiotic treatment based on a fructooligosaccharide, Lactobacillus, and Bifidobacterium composition produced an alteration in the Th2 serological immune profile in the direction of Th1 and improved pain symptomatology. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Profile Analysis of Psychological Symptoms Associated With Misophonia: A Community Sample.

PubMed

McKay, Dean; Kim, Se-Kang; Mancusi, Lauren; Storch, Eric A; Spankovich, Christopher

2018-03-01

Misophonia is characterized by extreme aversive reactions to certain classes of sounds. It has recently been recognized as a condition associated with significant disability. Research has begun to evaluate psychopathological correlates of misophonia. This study sought to identify profiles of psychopathology that characterize misophonia in a large community sample. A total of N = 628 adult participants completed a battery of measures assessing anxiety and anxiety sensitivity, depression, stress responses, anger, dissociative experiences, obsessive-compulsive symptoms and beliefs, distress tolerance, bodily perceptions, as well as misophonia severity. Profile Analysis via Multidimensional Scaling (PAMS) was employed to evaluate profiles associated with elevated misophonia and those without symptoms. Three profiles were extracted. The first two accounted for 70% total variance and did not show distinctions between groups. The third profile accounted for 11% total variance, and showed that misophonia is associated with lower obsessive-compulsive symptoms for neutralizing, obsessions generally, and washing compared to those not endorsing misophonia, and higher levels of obsessive-compulsive symptoms associated with ordering and harm avoidance. This third profile extracted also showed significant differences between those with and without misophonia on the scale assessing physical concerns (that is, sensitivity to interoceptive sensations) as assessed with the ASI-3. Further research is called for involving diagnostic interviewing and experimental methods to clarify these putative mechanisms associated with misophonia. Copyright © 2017. Published by Elsevier Ltd.

Transcriptome Analysis of Spartina pectinata in Response to Freezing Stress

PubMed Central

Nah, Gyoungju; Lee, Moonsub; Kim, Do-Soon; Rayburn, A. Lane; Voigt, Thomas; Lee, D. K.

2016-01-01

Prairie cordgrass (Spartina pectinata), a perennial C4 grass native to the North American prairie, has several distinctive characteristics that potentially make it a model crop for production in stressful environments. However, little is known about the transcriptome dynamics of prairie cordgrass despite its unique freezing stress tolerance. Therefore, the purpose of this work was to explore the transcriptome dynamics of prairie cordgrass in response to freezing stress at -5°C for 5 min and 30 min. We used a RNA-sequencing method to assemble the S. pectinata leaf transcriptome and performed gene-expression profiling of the transcripts under freezing treatment. Six differentially expressed gene (DEG) groups were categorized from the profiling. In addition, two major consecutive orders of gene expression were observed in response to freezing; the first being the acute up-regulation of genes involved in plasma membrane modification, calcium-mediated signaling, proteasome-related proteins, and transcription regulators (e.g., MYB and WRKY). The follow-up and second response was of genes involved in encoding the putative anti-freezing protein and the previously known DNA and cell-damage-repair proteins. Moreover, we identified the genes involved in epigenetic regulation and circadian-clock expression. Our results indicate that freezing response in S. pectinata reflects dynamic changes in rapid-time duration, as well as in metabolic, transcriptional, post-translational, and epigenetic regulation. PMID:27032112

Sampling-based Bayesian approaches reveal the importance of quasi-bistable behavior in cellular decision processes on the example of the MAPK signaling pathway in PC-12 cell lines.

PubMed

Jensch, Antje; Thomaseth, Caterina; Radde, Nicole E

2017-01-25

Positive and negative feedback loops are ubiquitous motifs in biochemical signaling pathways. The mitogen-activated protein kinase (MAPK) pathway module is part of many distinct signaling networks and comprises several of these motifs, whose functioning depends on the cell line at hand and on the particular context. The maintainance of specificity of the response of the MAPK module to distinct stimuli has become a key paradigm especially in PC-12 cells, where the same module leads to different cell fates, depending on the stimulating growth factor. This cell fate is regulated by differences in the ERK (MAPK) activation profile, which shows a transient response upon stimulation with EGF, while the response is sustained in case of NGF. This behavior was explained by different effective network topologies. It is widely believed that this sustained response requires a bistable system. In this study we present a sampling-based Bayesian model analysis on a dataset, in which PC-12 cells have been stimulated with different growth factors. This is combined with novel analysis methods to investigate the role of feedback interconnections to shape ERK response. Results strongly suggest that, besides bistability, an additional effect called quasi-bistability can contribute to explain the observed responses of the system to different stimuli. Quasi-bistability is the ability of a monostable system to maintain two distinct states over a long time period upon a transient signal, which is also related to positive feedback, but cannot be detected by standard steady state analysis methods. Although applied on a specific example, our framework is generic enough to be also relevant for other regulatory network modeling studies that comprise positive feedback to explain cellular decision making processes. Overall, this study advices to focus not only on steady states, but also to take transient behavior into account in the analysis.

PROSPECT: Profiling of Resistance Patterns Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax and Therapeutic Target Identification

DTIC Science & Technology

2011-06-01

8w DC in patients treated with erlotinib, but not sorafenib, indicating that it is not merely a prognostic signature; D) Both the 5-gene signature...disease-free, progression-free, and overall survival will vary across prognostically distinct groups. 3. Specific molecular signatures in primary tumors...therapeutic strategies at relapse. Specific Aims: Aim 1: To define characteristic TTF/gene expression profiles of prognostically distinct

Identification of proteomic signatures associated with lung cancer and COPD.

PubMed

Pastor, M D; Nogal, A; Molina-Pinelo, S; Meléndez, R; Salinas, A; González De la Peña, M; Martín-Juan, J; Corral, J; García-Carbonero, R; Carnero, A; Paz-Ares, L

2013-08-26

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. The aim of this study was to identify distinct proteomic profiles able to discriminate these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC without COPD, and control with neither COPD nor LC. Proteins were separated into spots by bidimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 40 proteins were differentially expressed in the LC and/or COPD groups as compared with the control group. Distinct protein profiles were identified and validated for each pathological entity (LC and COPD). The main networks involved were related to inflammatory signalling, free radical scavenging and oxidative stress response, and glycolysis and gluconeogenesis pathways. The most relevant signalling link between LC and COPD was through the NF-κB pathway. In conclusion, the protein profiles identified contribute to elucidate the underlying pathogenic pathways of both diseases, and provide new tools of potential use as biomarkers for the early diagnosis of LC. Sequence coverage. The protein sequence coverage (95%) was estimated for specific proteins by the percentage of matching amino acids from the identified peptides having confidence greater than or equal to 95% divided by the total number of amino acids in the sequence. Ingenuity Pathways Analysis. Mapping of our proteins onto biological pathways and disease networks demonstrated that 22 proteins were linked to inflammatory signalling (p-value: 1.35 10(-08)-1.42 10(-02)), 15 proteins were associated with free radical scavenging and oxidative stress response (p-value: 4.93 10(-11)-1.27 10(-02)), and 9 proteins were related with glycolysis and gluconeogenesis pathways (p-value: 7.39 10(-09)-1.58 10(-02)). Copyright © 2013 Elsevier B.V. All rights reserved.

Temperament Type Specific Metabolite Profiles of the Prefrontal Cortex and Serum in Cattle

PubMed Central

Brand, Bodo; Hadlich, Frieder; Brandt, Bettina; Schauer, Nicolas; Graunke, Katharina L.; Langbein, Jan; Repsilber, Dirk; Ponsuksili, Siriluk; Schwerin, Manfred

2015-01-01

In the past decade the number of studies investigating temperament in farm animals has increased greatly because temperament has been shown not only to affect handling but also reproduction, health and economically important production traits. However, molecular pathways underlying temperament and molecular pathways linking temperament to production traits, health and reproduction have yet to be studied in full detail. Here we report the results of metabolite profiling of the prefrontal cortex and serum of cattle with distinct temperament types that were performed to further explore their molecular divergence in the response to the slaughter procedure and to identify new targets for further research of cattle temperament. By performing an untargeted comprehensive metabolite profiling, 627 and 1097 metabolite features comprising 235 and 328 metabolites could be detected in the prefrontal cortex and serum, respectively. In total, 54 prefrontal cortex and 51 serum metabolite features were indicated to have a high relevance in the classification of temperament types by a sparse partial least square discriminant analysis. A clear discrimination between fearful/neophobic-alert, interested-stressed, subdued/uninterested-calm and outgoing/neophilic-alert temperament types could be observed based on the abundance of the identified relevant prefrontal cortex and serum metabolites. Metabolites with high relevance in the classification of temperament types revealed that the main differences between temperament types in the response to the slaughter procedure were related to the abundance of glycerophospholipids, fatty acyls and sterol lipids. Differences in the abundance of metabolites related to C21 steroid metabolism and oxidative stress indicated that the differences in the metabolite profiles of the four extreme temperament types could be the result of a temperament type specific regulation of molecular pathways that are known to be involved in the stress and fear response. PMID:25927228

Temperament type specific metabolite profiles of the prefrontal cortex and serum in cattle.

PubMed

Brand, Bodo; Hadlich, Frieder; Brandt, Bettina; Schauer, Nicolas; Graunke, Katharina L; Langbein, Jan; Repsilber, Dirk; Ponsuksili, Siriluk; Schwerin, Manfred

2015-01-01

In the past decade the number of studies investigating temperament in farm animals has increased greatly because temperament has been shown not only to affect handling but also reproduction, health and economically important production traits. However, molecular pathways underlying temperament and molecular pathways linking temperament to production traits, health and reproduction have yet to be studied in full detail. Here we report the results of metabolite profiling of the prefrontal cortex and serum of cattle with distinct temperament types that were performed to further explore their molecular divergence in the response to the slaughter procedure and to identify new targets for further research of cattle temperament. By performing an untargeted comprehensive metabolite profiling, 627 and 1097 metabolite features comprising 235 and 328 metabolites could be detected in the prefrontal cortex and serum, respectively. In total, 54 prefrontal cortex and 51 serum metabolite features were indicated to have a high relevance in the classification of temperament types by a sparse partial least square discriminant analysis. A clear discrimination between fearful/neophobic-alert, interested-stressed, subdued/uninterested-calm and outgoing/neophilic-alert temperament types could be observed based on the abundance of the identified relevant prefrontal cortex and serum metabolites. Metabolites with high relevance in the classification of temperament types revealed that the main differences between temperament types in the response to the slaughter procedure were related to the abundance of glycerophospholipids, fatty acyls and sterol lipids. Differences in the abundance of metabolites related to C21 steroid metabolism and oxidative stress indicated that the differences in the metabolite profiles of the four extreme temperament types could be the result of a temperament type specific regulation of molecular pathways that are known to be involved in the stress and fear response.

Long-lasting stem cell-like memory CD8+ T cells with a naïve-like profile upon yellow fever vaccination.

PubMed

Fuertes Marraco, Silvia A; Soneson, Charlotte; Cagnon, Laurène; Gannon, Philippe O; Allard, Mathilde; Abed Maillard, Samia; Montandon, Nicole; Rufer, Nathalie; Waldvogel, Sophie; Delorenzi, Mauro; Speiser, Daniel E

2015-04-08

Efficient and persisting immune memory is essential for long-term protection from infectious and malignant diseases. The yellow fever (YF) vaccine is a live attenuated virus that mediates lifelong protection, with recent studies showing that the CD8(+) T cell response is particularly robust. Yet, limited data exist regarding the long-term CD8(+) T cell response, with no studies beyond 5 years after vaccination. We investigated 41 vaccinees, spanning 0.27 to 35 years after vaccination. YF-specific CD8(+) T cells were readily detected in almost all donors (38 of 41), with frequencies decreasing with time. As previously described, effector cells dominated the response early after vaccination. We detected a population of naïve-like YF-specific CD8(+) T cells that was stably maintained for more than 25 years and was capable of self-renewal ex vivo. In-depth analyses of markers and genome-wide mRNA profiling showed that naïve-like YF-specific CD8(+) T cells in vaccinees (i) were distinct from genuine naïve cells in unvaccinated donors, (ii) resembled the recently described stem cell-like memory subset (Tscm), and (iii) among all differentiated subsets, had profiles closest to naïve cells. Our findings reveal that CD8(+) Tscm are efficiently induced by a vaccine in humans, persist for decades, and preserve a naïveness-like profile. These data support YF vaccination as an optimal mechanistic model for the study of long-lasting memory CD8(+) T cells in humans. Copyright © 2015, American Association for the Advancement of Science.

Person-oriented methods in partner violence research: distinct biopsychosocial profiles among battered women.

PubMed

Nurius, Paula S; Macy, Rebecca J

2010-06-01

Violence researchers have called for the use of person-oriented methods to understand differences that have been found in biopsychosocial consequences among those who experience intimate partner violence (IPV). To address this issue, we apply a person-oriented statistical method, latent profile analysis (LPA), to test for meaningful subgroups of a sample of 448 battered women based on participants' appraisals of their vulnerability relative to their violent partner, depressive symptoms, physical injuries, overall physical health functioning, and their positive and negative social relationships with friends and family. The LPA established five significantly distinct subgroups. Using MANOVA, we examined these subgroups and their respective IPV exposure, both concomitant and separate incidents within the past year. Those with the most intensive violence exposure show the greatest level of challenge and impairment. However, the groups with comparable levels of IPV exposure manifest distinctly different configurations of biopsychosocial profiles, indicating a need for adaptive interventions commensurate with these profiles. We discuss the implications these findings have for developing adaptive interventions for battered women, as well as the potential utility of person-oriented tools for violence researchers.

Person-Oriented Methods in Partner Violence Research: Distinct Biopsychosocial Profiles Among Battered Women

PubMed Central

Nurius, Paula S.; Macy, Rebecca J.

2014-01-01

Violence researchers have called for the use of person-oriented methods to understand differences that have been found in biopsychosocial consequences among those who experience intimate partner violence (IPV). To address this issue, we apply a person-oriented statistical method, latent profile analysis (LPA), to test for meaningful subgroups of a sample of 448 battered women based on participants’ appraisals of their vulnerability relative to their violent partner, depressive symptoms, physical injuries, overall physical health functioning, and their positive and negative social relationships with friends and family. The LPA established five significantly distinct subgroups. Using MANOVA, we examined these subgroups and their respective IPV exposure, both concomitant and separate incidents within the past year. Those with the most intensive violence exposure show the greatest level of challenge and impairment. However, the groups with comparable levels of IPV exposure manifest distinctly different configurations of biopsychosocial profiles, indicating a need for adaptive interventions commensurate with these profiles. We discuss the implications these findings have for developing adaptive interventions for battered women, as well as the potential utility of person-oriented tools for violence researchers. PMID:19897777

Metabolite Profiling of Low-P Tolerant and Low-P Sensitive Maize Genotypes under Phosphorus Starvation and Restoration Conditions

PubMed Central

Ganie, Arshid Hussain; Ahmad, Altaf; Pandey, Renu; Aref, Ibrahim M.; Yousuf, Peerzada Yasir; Ahmad, Sayeed; Iqbal, Muhammad

2015-01-01

Background Maize (Zea mays L.) is one of the most widely cultivated crop plants. Unavoidable economic and environmental problems associated with the excessive use of phosphatic fertilizers demands its better management. The solution lies in improving the phosphorus (P) use efficiency to sustain productivity even at low P levels. Untargeted metabolomic profiling of contrasting genotypes provides a snap shot of whole metabolome which differs under specific conditions. This information provides an understanding of the mechanisms underlying tolerance to P stress and the approach for increasing P-use-efficiency. Methodology/Principal Findings A comparative metabolite-profiling approach based on gas chromatography-mass spectrometry (GC/MS) was applied to investigate the effect of P starvation and its restoration in low-P sensitive (HM-4) and low-P tolerant (PEHM-2) maize genotypes. A comparison of the metabolite profiles of contrasting genotypes in response to P-deficiency revealed distinct differences among low-P sensitive and tolerant genotypes. Another set of these genotypes were grown under P-restoration condition and sampled at different time intervals (3, 5 and 10 days) to investigate if the changes in metabolite profile under P-deficiency was restored. Significant variations in the metabolite pools of these genotypes were observed under P-deficiency which were genotype specific. Out of 180 distinct analytes, 91 were identified. Phosphorus-starvation resulted in accumulation of di- and trisaccharides and metabolites of ammonium metabolism, specifically in leaves, but decreased the levels of phosphate-containing metabolites and organic acids. A sharp increase in the concentrations of glutamine, asparagine, serine and glycine was observed in both shoots and roots under low-P condition. Conclusion The new insights generated on the maize metabolome in resposne to P-starvation and restoration would be useful towards improvement of the P-use efficiency in maize. PMID:26090681

Functional transformations of odor inputs in the mouse olfactory bulb.

PubMed

Adam, Yoav; Livneh, Yoav; Miyamichi, Kazunari; Groysman, Maya; Luo, Liqun; Mizrahi, Adi

2014-01-01

Sensory inputs from the nasal epithelium to the olfactory bulb (OB) are organized as a discrete map in the glomerular layer (GL). This map is then modulated by distinct types of local neurons and transmitted to higher brain areas via mitral and tufted cells. Little is known about the functional organization of the circuits downstream of glomeruli. We used in vivo two-photon calcium imaging for large scale functional mapping of distinct neuronal populations in the mouse OB, at single cell resolution. Specifically, we imaged odor responses of mitral cells (MCs), tufted cells (TCs) and glomerular interneurons (GL-INs). Mitral cells population activity was heterogeneous and only mildly correlated with the olfactory receptor neuron (ORN) inputs, supporting the view that discrete input maps undergo significant transformations at the output level of the OB. In contrast, population activity profiles of TCs were dense, and highly correlated with the odor inputs in both space and time. Glomerular interneurons were also highly correlated with the ORN inputs, but showed higher activation thresholds suggesting that these neurons are driven by strongly activated glomeruli. Temporally, upon persistent odor exposure, TCs quickly adapted. In contrast, both MCs and GL-INs showed diverse temporal response patterns, suggesting that GL-INs could contribute to the transformations MCs undergo at slow time scales. Our data suggest that sensory odor maps are transformed by TCs and MCs in different ways forming two distinct and parallel information streams.

The IFN Response in Bats Displays Distinctive IFN-Stimulated Gene Expression Kinetics with Atypical RNASEL Induction.

PubMed

De La Cruz-Rivera, Pamela C; Kanchwala, Mohammed; Liang, Hanquan; Kumar, Ashwani; Wang, Lin-Fa; Xing, Chao; Schoggins, John W

2018-01-01

Bats host a large number of zoonotic viruses, including several viruses that are highly pathogenic to other mammals. The mechanisms underlying this rich viral diversity are unknown, but they may be linked to unique immunological features that allow bats to act as asymptomatic viral reservoirs. Vertebrates respond to viral infection by inducing IFNs, which trigger antiviral defenses through IFN-stimulated gene (ISG) expression. Although the IFN system of several bats is characterized at the genomic level, less is known about bat IFN-mediated transcriptional responses. In this article, we show that IFN signaling in bat cells from the black flying fox ( Pteropus alecto ) consists of conserved and unique ISG expression profiles. In IFN-stimulated cells, bat ISGs comprise two unique temporal subclusters with similar early induction kinetics but distinct late-phase declines. In contrast, human ISGs lack this decline phase and remained elevated for longer periods. Notably, in unstimulated cells, bat ISGs were expressed more highly than their human counterparts. We also found that the antiviral effector 2-5A-dependent endoribonuclease, which is not an ISG in humans, is highly IFN inducible in black flying fox cells and contributes to cell-intrinsic control of viral infection. These studies reveal distinctive innate immune features that may underlie a unique virus-host relationship in bats. Copyright © 2017 by The American Association of Immunologists, Inc.

Hoarding in obsessive-compulsive disorder: clinical and genetic correlates.

PubMed

Lochner, Christine; Kinnear, Craig J; Hemmings, Sian M J; Seller, Cathlene; Niehaus, Dana J H; Knowles, James A; Daniels, Willie; Moolman-Smook, Johanna C; Seedat, Soraya; Stein, Dan J

2005-09-01

Hoarding may be an important symptom dimension in obsessive-compulsive disorder (OCD). Hoarding in OCD has been associated with poor insight, poorer response to selective serotonin reuptake inhibitors than other OCD symptom dimensions, and a distinctive psychobiological profile. The clinical and genetic correlates of hoarding in OCD therefore deserve additional investigation. Adult OCD patients (N = 315) underwent a comprehensive clinical assessment that included the Structured Clinical Interview for DSM-IV Axis I Disorders (Patient Edition) and for Diagnosis of Obsessive-Compulsive Spectrum Disorders. DNA extracted from venous blood (10-30 mL) in a Caucasian subset of the interviewed OCD patients (N = 204) and Caucasian controls (N = 169), including patients (N = 94) and controls (N = 138) of Afrikaner descent, was genotyped to investigate polymorphisms in genes involved in monoamine function and previously hypothesized to be relevant to OCD. Data were collected from 1998 through 2004. OCD patients with hoarding made up 18.1% of the total sample. Compared with nonhoarding OCD, OCD with hoarding was associated with a number of comorbid Axis I disorders, obsessive-compulsive personality disorder, significantly higher OCD severity scores, and more functional impairment. In subjects of Afrikaner descent, the L/L genotype of the COMT Val158Met polymorphism was significantly more common in the OCD hoarding group, with a preponderance of low activity alleles, compared with nonhoarding patients and controls. These data are consistent with the hypothesis that hoarding represents a unique symptom subtype in OCD with a distinctive clinical and psychobiological profile. Further work is needed to determine the psychobiological mechanisms responsible for hoarding and to replicate the genetic findings noted here.

Ixodes ricinus Tick Lipocalins: Identification, Cloning, Phylogenetic Analysis and Biochemical Characterization

PubMed Central

Beaufays, Jérôme; Adam, Benoît; Decrem, Yves; Prévôt, Pierre-Paul; Santini, Sébastien; Brasseur, Robert; Brossard, Michel; Lins, Laurence

2008-01-01

Background During their blood meal, ticks secrete a wide variety of proteins that interfere with their host's defense mechanisms. Among these proteins, lipocalins play a major role in the modulation of the inflammatory response. Methodology/Principal Findings Screening a cDNA library in association with RT-PCR and RACE methodologies allowed us to identify 14 new lipocalin genes in the salivary glands of the Ixodes ricinus hard tick. A computational in-depth structural analysis confirmed that LIRs belong to the lipocalin family. These proteins were called LIR for “Lipocalin from I. ricinus” and numbered from 1 to 14 (LIR1 to LIR14). According to their percentage identity/similarity, LIR proteins may be assigned to 6 distinct phylogenetic groups. The mature proteins have calculated pM and pI varying from 21.8 kDa to 37.2 kDa and from 4.45 to 9.57 respectively. In a western blot analysis, all recombinant LIRs appeared as a series of thin bands at 50–70 kDa, suggesting extensive glycosylation, which was experimentally confirmed by treatment with N-glycosidase F. In addition, the in vivo expression analysis of LIRs in I. ricinus, examined by RT-PCR, showed homogeneous expression profiles for certain phylogenetic groups and relatively heterogeneous profiles for other groups. Finally, we demonstrated that LIR6 codes for a protein that specifically binds leukotriene B4. Conclusions/Significance This work confirms that, regarding their biochemical properties, expression profile, and sequence signature, lipocalins in Ixodes hard tick genus, and more specifically in the Ixodes ricinus species, are segregated into distinct phylogenetic groups suggesting potential distinct function. This was particularly demonstrated by the ability of LIR6 to scavenge leukotriene B4. The other LIRs did not bind any of the ligands tested, such as 5-hydroxytryptamine, ADP, norepinephrine, platelet activating factor, prostaglandins D2 and E2, and finally leukotrienes B4 and C4. PMID:19096708

Functional Characterization of FLT3 Receptor Signaling Deregulation in Acute Myeloid Leukemia by Single Cell Network Profiling (SCNP)

PubMed Central

Rosen, David B.; Minden, Mark D.; Kornblau, Steven M.; Cohen, Aileen; Gayko, Urte; Putta, Santosh; Woronicz, John; Evensen, Erik; Fantl, Wendy J.; Cesano, Alessandra

2010-01-01

Background Molecular characterization of the FMS-like tyrosine kinase 3 receptor (FLT3) in cytogenetically normal acute myeloid leukemia (AML) has recently been incorporated into clinical guidelines based on correlations between FLT3 internal tandem duplications (FLT3-ITD) and decreased disease-free and overall survival. These mutations result in constitutive activation of FLT3, and FLT3 inhibitors are currently undergoing trials in AML patients selected on FLT3 molecular status. However, the transient and partial responses observed suggest that FLT3 mutational status alone does not provide complete information on FLT3 biological activity at the individual patient level. Examination of variation in cellular responsiveness to signaling modulation may be more informative. Methodology/Principal Findings Using single cell network profiling (SCNP), cells were treated with extracellular modulators and their functional responses were quantified by multiparametric flow cytometry. Intracellular signaling responses were compared between healthy bone marrow myeloblasts (BMMb) and AML leukemic blasts characterized as FLT3 wild type (FLT3-WT) or FLT3-ITD. Compared to healthy BMMb, FLT3-WT leukemic blasts demonstrated a wide range of signaling responses to FLT3 ligand (FLT3L), including elevated and sustained PI3K and Ras/Raf/Erk signaling. Distinct signaling and apoptosis profiles were observed in FLT3-WT and FLT3-ITD AML samples, with more uniform signaling observed in FLT3-ITD AML samples. Specifically, increased basal p-Stat5 levels, decreased FLT3L induced activation of the PI3K and Ras/Raf/Erk pathways, decreased IL-27 induced activation of the Jak/Stat pathway, and heightened apoptotic responses to agents inducing DNA damage were observed in FLT3-ITD AML samples. Preliminary analysis correlating these findings with clinical outcomes suggests that classification of patient samples based on signaling profiles may more accurately reflect FLT3 signaling deregulation and provide additional information for disease characterization and management. Conclusions/Significance These studies show the feasibility of SCNP to assess modulated intracellular signaling pathways and characterize the biology of individual AML samples in the context of genetic alterations. PMID:21048955

A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors Reveals Molecular Subtypes with Distinctive Clinical, Metastatic, Developmental, and Metabolic Characteristics

PubMed Central

Sadanandam, Anguraj; Wullschleger, Stephan; Lyssiotis, Costas A.; Grötzinger, Carsten; Barbi, Stefano; Bersani, Samantha; Körner, Jan; Wafy, Ismael; Mafficini, Andrea; Lawlor, Rita T.; Simbolo, Michele; Asara, John M.; Bläker, Hendrik; Cantley, Lewis C.; Wiedenmann, Bertram; Scarpa, Aldo; Hanahan, Douglas

2016-01-01

Seeking to assess the representative and instructive value of an engineered mouse model of pancreatic neuroendocrine tumors (PanNET) for its cognate human cancer, we profiled and compared mRNA and miRNA transcriptomes of tumors from both. Mouse PanNET tumors could be classified into two distinctive subtypes, well-differentiated islet/insulinoma tumors (IT) and poorly differentiated tumors associated with liver metastases, dubbed metastasis-like primary (MLP). Human PanNETs were independently classified into these same two subtypes, along with a third, specific gene mutation–enriched subtype. The MLP subtypes in human and mouse were similar to liver metastases in terms of miRNA and mRNA transcriptome profiles and signature genes. The human/mouse MLP subtypes also similarly expressed genes known to regulate early pancreas development, whereas the IT subtypes expressed genes characteristic of mature islet cells, suggesting different tumorigenesis pathways. In addition, these subtypes exhibit distinct metabolic profiles marked by differential pyruvate metabolism, substantiating the significance of their separate identities. SIGNIFICANCE This study involves a comprehensive cross-species integrated analysis of multi-omics profiles and histology to stratify PanNETs into subtypes with distinctive characteristics. We provide support for the RIP1-TAG2 mouse model as representative of its cognate human cancer with prospects to better understand PanNET heterogeneity and consider future applications of personalized cancer therapy. PMID:26446169

A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors Reveals Molecular Subtypes with Distinctive Clinical, Metastatic, Developmental, and Metabolic Characteristics.

PubMed

Sadanandam, Anguraj; Wullschleger, Stephan; Lyssiotis, Costas A; Grötzinger, Carsten; Barbi, Stefano; Bersani, Samantha; Körner, Jan; Wafy, Ismael; Mafficini, Andrea; Lawlor, Rita T; Simbolo, Michele; Asara, John M; Bläker, Hendrik; Cantley, Lewis C; Wiedenmann, Bertram; Scarpa, Aldo; Hanahan, Douglas

2015-12-01

Seeking to assess the representative and instructive value of an engineered mouse model of pancreatic neuroendocrine tumors (PanNET) for its cognate human cancer, we profiled and compared mRNA and miRNA transcriptomes of tumors from both. Mouse PanNET tumors could be classified into two distinctive subtypes, well-differentiated islet/insulinoma tumors (IT) and poorly differentiated tumors associated with liver metastases, dubbed metastasis-like primary (MLP). Human PanNETs were independently classified into these same two subtypes, along with a third, specific gene mutation-enriched subtype. The MLP subtypes in human and mouse were similar to liver metastases in terms of miRNA and mRNA transcriptome profiles and signature genes. The human/mouse MLP subtypes also similarly expressed genes known to regulate early pancreas development, whereas the IT subtypes expressed genes characteristic of mature islet cells, suggesting different tumorigenesis pathways. In addition, these subtypes exhibit distinct metabolic profiles marked by differential pyruvate metabolism, substantiating the significance of their separate identities. This study involves a comprehensive cross-species integrated analysis of multi-omics profiles and histology to stratify PanNETs into subtypes with distinctive characteristics. We provide support for the RIP1-TAG2 mouse model as representative of its cognate human cancer with prospects to better understand PanNET heterogeneity and consider future applications of personalized cancer therapy. ©2015 American Association for Cancer Research.

Identifying dentists' attitudes towards prevention guidance using Q-sort methodology.

PubMed

Witton, R V; Moles, D R

2015-06-01

To gain insight into the attitudes and motivating factors of dentists working in the English National Health Service (NHS) towards prevention guidance. Q-methodology: an established hybrid quantitative/qualitative technique used in the social sciences to categorise subjects based on their views by considering factors as part of their overall decision-making profile. General Dental Practices offering care under an NHS contract. NHS dentists (n = 26) placed 36 statements about prevention guidance derived from an earlier study into a distribution grid that ranked the statements from "most agree" to "most disagree". Principal components factor analysis was applied to determine the principal patterns in the rankings of statements. Analysis indicated a total of six distinct profiles within the responses, of which three profiles had at least six dentists loading onto them. The first profile was strongly characterised by dentists who appear motivated to provide prevention but financial and time constraints prevent them from doing so. The second was characterised by dentists using prevention guidance but restricting its use to only certain patients. The third was characterised by dentists who appeared "health-focused". They placed importance on working to prevention guidance, but were keen to have greater patient and professional support in achieving this. In this group of dentists Q-methodology identified three main profiles to the delivery of prevention guidance.

Mastitis Pathogens with High Virulence in a Mouse Model Produce a Distinct Cytokine Profile In Vivo

PubMed Central

Johnzon, Carl-Fredrik; Artursson, Karin; Söderlund, Robert; Guss, Bengt; Rönnberg, Elin; Pejler, Gunnar

2016-01-01

Mastitis is a serious medical condition of dairy cattle. Here, we evaluated whether the degree of virulence of mastitis pathogens in a mouse model can be linked to the inflammatory response that they provoke. Clinical isolates of Staphylococcus aureus (S. aureus) (strain 556 and 392) and Escherichia coli (E. coli) (676 and 127), and laboratory control strains [8325-4 (S. aureus) and MG1655 (E. coli)], were injected i.p. into mice, followed by the assessment of clinical scores and inflammatory parameters. As judged by clinical scoring, E. coli 127 exhibited the largest degree of virulence among the strains. All bacterial strains induced neutrophil recruitment. However, whereas E. coli 127 induced high peritoneal levels of CXCL1, G-CSF, and CCL2, strikingly lower levels of these were induced by the less virulent bacterial strains. High concentrations of these compounds were also seen in blood samples taken from animals infected with E. coli 127, suggesting systemic inflammation. Moreover, the levels of CXCL1 and G-CSF, both in the peritoneal fluid and in plasma, correlated with clinical score. Together, these findings suggest that highly virulent clinical mastitis isolates produce a distinct cytokine profile that shows a close correlation with the severity of the bacterial infection. PMID:27713743

DNA Methylation Profiles of Selected Pro-Inflammatory Cytokines in Alzheimer Disease.

PubMed

Nicolia, Vincenzina; Cavallaro, Rosaria A; López-González, Irene; Maccarrone, Mauro; Scarpa, Sigfrido; Ferrer, Isidre; Fuso, Andrea

2017-01-01

By means of functional genomics analysis, we recently described the mRNA expression profiles of various genes involved in the neuroinflammatory response in the brains of subjects with late-onset Alzheimer Disease (LOAD). Some of these genes, namely interleukin (IL)-1β and IL-6, showed distinct expression profiles with peak expression during the first stages of the disease and control-like levels at later stages. IL-1β and IL-6 genes are modulated by DNA methylation in different chronic and degenerative diseases; it is also well known that LOAD may have an epigenetic basis. Indeed, we and others have previously reported gene-specific DNA methylation alterations in LOAD and in related animal models. Based on these data, we studied the DNA methylation profiles, at single cytosine resolution, of IL-1β and IL-6 5'-flanking region by bisulphite modification in the cortex of healthy controls and LOAD patients at 2 different disease stages: Braak I-II/A and Braak V-VI/C. Our analysis provides evidence that neuroinflammation in LOAD is associated with (and possibly mediated by) epigenetic modifications. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Profile of an excellent nurse manager: identifying and developing health care team leaders.

PubMed

Kallas, Kathryn D

2014-01-01

The purpose of this research was to identify the profile of an excellent nurse manager who can lead effective health care teams. Leadership attributes and competencies that characterize an excellent nurse manager and tools to identify them are lacking in the literature but are required to efficiently and effectively address the growing shortage of registered nurses (RNs) in health care team leadership roles and the critical linkage of these roles to patient outcomes. A profile of an excellent nurse manager was developed on the basis of the responses of nurse managers across the United States who had been identified as excellent or competent by chief nurse executive assessment or/and the Nurse Manager Ability, Leadership, and Support of Nurses staff survey to the Kouzes and Posner Leadership Practices Inventory: Self Instrument. Statistically significant distinctions exist between nurse managers who are excellent and those who are competent as assessed by the Five Practices of Exemplary Leadership, which together comprise the profile of an excellent nurse manager. The Kouzes and Posner Leadership Practices Inventory: Self Instrument can be used to identify, recruit, and develop RNs in the nurse manager role as excellent leaders of effective health care teams.

Use of mutation profiles to refine the classification of endometrial carcinomas.

PubMed

McConechy, Melissa K; Ding, Jiarui; Cheang, Maggie Cu; Wiegand, Kimberly; Senz, Janine; Tone, Alicia; Yang, Winnie; Prentice, Leah; Tse, Kane; Zeng, Thomas; McDonald, Helen; Schmidt, Amy P; Mutch, David G; McAlpine, Jessica N; Hirst, Martin; Shah, Sohrab P; Lee, Cheng-Han; Goodfellow, Paul J; Gilks, C Blake; Huntsman, David G

2012-09-01

The classification of endometrial carcinomas is based on pathological assessment of tumour cell type; the different cell types (endometrioid, serous, carcinosarcoma, mixed, undifferentiated, and clear cell) are associated with distinct molecular alterations. This current classification system for high-grade subtypes, in particular the distinction between high-grade endometrioid (EEC-3) and serous carcinomas (ESC), is limited in its reproducibility and prognostic abilities. Therefore, a search for specific molecular classifiers to improve endometrial carcinoma subclassification is warranted. We performed target enrichment sequencing on 393 endometrial carcinomas from two large cohorts, sequencing exons from the following nine genes: ARID1A, PPP2R1A, PTEN, PIK3CA, KRAS, CTNNB1, TP53, BRAF, and PPP2R5C. Based on this gene panel, each endometrial carcinoma subtype shows a distinct mutation profile. EEC-3s have significantly different frequencies of PTEN and TP53 mutations when compared to low-grade endometrioid carcinomas. ESCs and EEC-3s are distinct subtypes with significantly different frequencies of mutations in PTEN, ARID1A, PPP2R1A, TP53, and CTNNB1. From the mutation profiles, we were able to identify subtype outliers, ie cases diagnosed morphologically as one subtype but with a mutation profile suggestive of a different subtype. Careful review of these diagnostically challenging cases suggested that the original morphological classification was incorrect in most instances. The molecular profile of carcinosarcomas suggests two distinct mutation profiles for these tumours: endometrioid-type (PTEN, PIK3CA, ARID1A, KRAS mutations) and serous-type (TP53 and PPP2R1A mutations). While this nine-gene panel does not allow for a purely molecularly based classification of endometrial carcinoma, it may prove useful as an adjunct to morphological classification and serve as an aid in the classification of problematic cases. If used in practice, it may lead to improved diagnostic reproducibility and may also serve to stratify patients for targeted therapeutics. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Domestication affects the structure, development and stability of biobehavioural profiles.

PubMed

Kaiser, Sylvia; Hennessy, Michael B; Sachser, Norbert

2015-01-01

Domestication is an evolutionary process during which the biobehavioural profile (comprising e.g. social and emotional behaviour, cognitive abilities, as well as hormonal stress responses) is substantially reshaped. Using a comparative approach, and focusing mainly on the domestic and wild guinea pig, an established model system for the study of domestication, we review (a) how wild and domestic animals of the same species differ in behaviour, emotion, cognition, and hormonal stress responses, (b) during which phases of life differences in biobehavioural profiles emerge and (c) whether or not animal personalities exist in both the wild and domestic form. Concerning (a), typical changes with domestication include increased courtship, sociopositive and maternal behaviours as well as decreased aggression and attentive behaviour. In addition, domestic animals display more anxiety-like and less risk-taking and exploratory behaviour than the wild form and they show distinctly lower endocrine stress responsiveness. There are no indications, however, that domestic animals have diminished cognitive abilities relative to the wild form. The different biobehavioural profiles of the wild and domestic animals can be regarded as adaptations to the different environmental conditions under which they live, i.e., the natural habitat and artificial man-made housing conditions, respectively. Concerning (b), the comparison of infantile, adolescent and adult wild and domestic guinea pigs shows that the typical biobehavioural profile of the domestic form is already present during early phases of life, that is, during early adolescence and weaning. Thus, differences between the domestic and the wild form can be attributed to genetic alterations resulting from artificial selection, and likely to environmental influences during the pre- and perinatal phase. Interestingly, the frequency of play behaviour does not differ between the domestic and wild form early in life, but is significantly higher in domesticated guinea pigs at later ages. Concerning (c), there is some evidence that personalities occur in both wild and domestic animals. However, there may be differences in which behavioural domains - social and sexual behaviour, emotionality, stress-responsiveness - are consistent over time. These differences are probably due to changing selection pressures during domestication.

Whole Tumor Histogram-profiling of Diffusion-Weighted Magnetic Resonance Images Reflects Tumorbiological Features of Primary Central Nervous System Lymphoma.

PubMed

Schob, Stefan; Münch, Benno; Dieckow, Julia; Quäschling, Ulf; Hoffmann, Karl-Titus; Richter, Cindy; Garnov, Nikita; Frydrychowicz, Clara; Krause, Matthias; Meyer, Hans-Jonas; Surov, Alexey

2018-04-01

Diffusion weighted imaging (DWI) quantifies motion of hydrogen nuclei in biological tissues and hereby has been used to assess the underlying tissue microarchitecture. Histogram-profiling of DWI provides more detailed information on diffusion characteristics of a lesion than the standardly calculated values of the apparent diffusion coefficient (ADC)-minimum, mean and maximum. Hence, the aim of our study was to investigate, which parameters of histogram-profiling of DWI in primary central nervous system lymphoma can be used to specifically predict features like cellular density, chromatin content and proliferative activity. Pre-treatment ADC maps of 21 PCNSL patients (8 female, 13 male, 28-89 years) from a 1.5T system were used for Matlab-based histogram profiling. Results of histopathology (H&E staining) and immunohistochemistry (Ki-67 expression) were quantified. Correlations between histogram-profiling parameters and neuropathologic examination were calculated using SPSS 23.0. The lower percentiles (p10 and p25) showed significant correlations with structural parameters of the neuropathologic examination (cellular density, chromatin content). The highest percentile, p90, correlated significantly with Ki-67 expression, resembling proliferative activity. Kurtosis of the ADC histogram correlated significantly with cellular density. Histogram-profiling of DWI in PCNSL provides a comprehensible set of parameters, which reflect distinct tumor-architectural and tumor-biological features, and hence, are promising biomarkers for treatment response and prognosis. Copyright © 2018. Published by Elsevier Inc.

Profiles of children's social-emotional health at school entry and associated income, gender and language inequalities: a cross-sectional population-based study in British Columbia, Canada.

PubMed

Thomson, Kimberly C; Guhn, Martin; Richardson, Chris G; Ark, Tavinder K; Shoveller, Jean

2017-07-26

Early identification of distinct patterns of child social-emotional strengths and vulnerabilities has the potential to improve our understanding of child mental health and well-being; however, few studies have explored natural groupings of indicators of child vulnerability and strengths at a population level. The purpose of this study was to examine heterogeneity in the patterns of young children's social and emotional health and investigate the extent to which sociodemographic characteristics were associated. Cross-sectional study based on a population-level cohort. All kindergarten children attending public schools between 2004 and 2007 in British Columbia (BC), Canada. 35 818 kindergarten children (age of 5 years) with available linked data from the Early Development Instrument (EDI), BC Ministry of Health and BC Ministry of Education. We used latent profile analysis (LPA) to identify distinct profiles of social-emotional health according to children's mean scores across eight social-emotional subscales on the EDI, a teacher-rated measure of children's early development. Subscales measured children's overall social competence, responsibility and respect, approaches to learning, readiness to explore, prosocial behaviour, anxiety, aggression and hyperactivity. Six social-emotional profiles were identified: (1) overall high social-emotional functioning, (2) inhibited-adaptive (3) uninhibited-adaptive, (4) inhibited-disengaged, (5) uninhibited-aggressive/hyperactive and (6) overall low social-emotional functioning. Boys, children with English as a second language (ESL) status and children with lower household income had higher odds of membership to the lower social-emotional functioning groups; however, this association was less negative among boys with ESL status. Over 40% of children exhibited some vulnerability in early social-emotional health, and profiles were associated with sociodemographic factors. Approximately 9% of children exhibited multiple co-occurring vulnerabilities. This study adds to our understanding of population-level distributions of children's early social-emotional health and identifies profiles of strengths and vulnerabilities that can inform future intervention efforts. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Profiles of children's social–emotional health at school entry and associated income, gender and language inequalities: a cross-sectional population-based study in British Columbia, Canada

PubMed Central

Guhn, Martin; Richardson, Chris G; Ark, Tavinder K; Shoveller, Jean

2017-01-01

Objectives Early identification of distinct patterns of child social–emotional strengths and vulnerabilities has the potential to improve our understanding of child mental health and well-being; however, few studies have explored natural groupings of indicators of child vulnerability and strengths at a population level. The purpose of this study was to examine heterogeneity in the patterns of young children's social and emotional health and investigate the extent to which sociodemographic characteristics were associated. Design Cross-sectional study based on a population-level cohort. Setting All kindergarten children attending public schools between 2004 and 2007 in British Columbia (BC), Canada. Participants 35 818 kindergarten children (age of 5 years) with available linked data from the Early Development Instrument (EDI), BC Ministry of Health and BC Ministry of Education. Outcome measure We used latent profile analysis (LPA) to identify distinct profiles of social–emotional health according to children's mean scores across eight social–emotional subscales on the EDI, a teacher-rated measure of children's early development. Subscales measured children's overall social competence, responsibility and respect, approaches to learning, readiness to explore, prosocial behaviour, anxiety, aggression and hyperactivity. Results Six social–emotional profiles were identified: (1) overall high social–emotional functioning, (2) inhibited-adaptive (3) uninhibited-adaptive, (4) inhibited-disengaged, (5) uninhibited-aggressive/hyperactive and (6) overall low social–emotional functioning. Boys, children with English as a second language (ESL) status and children with lower household income had higher odds of membership to the lower social–emotional functioning groups; however, this association was less negative among boys with ESL status. Conclusions Over 40% of children exhibited some vulnerability in early social–emotional health, and profiles were associated with sociodemographic factors. Approximately 9% of children exhibited multiple co-occurring vulnerabilities. This study adds to our understanding of population-level distributions of children's early social–emotional health and identifies profiles of strengths and vulnerabilities that can inform future intervention efforts. PMID:28751486

Victimization and health risk factors among weapon-carrying youth.

PubMed

Stayton, Catherine; McVeigh, Katharine H; Olson, E Carolyn; Perkins, Krystal; Kerker, Bonnie D

2011-11-01

To compare health risks of 2 subgroups of weapon carriers: victimized and nonvictimized youth. 2003-2007 NYC Youth Risk Behavior Surveys were analyzed using bivariate analyses and multinomial logistic regression. Among NYC teens, 7.5% reported weapon carrying without victimization; 6.9% reported it with victimization. Both subgroups were more likely than non-weapon carriers to binge drink, use marijuana, smoke, fight, and have multiple sex partners; weapon carriers with victimization also experienced persistent sadness and attempted suicide. Subgroups of weapon carriers have distinct profiles. Optimal response should pair disciplinary action with screening for behavioral and mental health concerns and victimization.

Impact of HPV in Oropharyngeal Cancer

PubMed Central

Marklund, Linda; Hammarstedt, Lalle

2011-01-01

The incidence of oropharyngeal cancers has increased in the western world and Human Papilloma Virus (HPV) has been recognised as a risk factor in the last decades. During the same period the prevalence of HPV in oropharyngeal tumours has increased and HPV has been suggested responsible for the increase. The HPV-positive tumours are today recognized as a distinct subset of head and neck cancers with its own clinopathological and risk profile and have a significantly improved prognosis regardless of treatment strategy. This review summarizes current knowledge regarding human papillomavirus biology, oncogenic mechanisms, risk factors, and impact of treatment. PMID:21234307

Do recognizable lifetime eating disorder phenotypes naturally occur in a culturally asian population? A combined latent profile and taxometric approach.

PubMed

Thomas, Jennifer J; Eddy, Kamryn T; Ruscio, John; Ng, King Lam; Casale, Kristen E; Becker, Anne E; Lee, Sing

2015-05-01

We examined whether empirically derived eating disorder (ED) categories in Hong Kong Chinese patients (N = 454) would be consistent with recognizable lifetime ED phenotypes derived from latent structure models of European and American samples. We performed latent profile analysis (LPA) using indicator variables from data collected during routine assessment, and then applied taxometric analysis to determine whether latent classes were qualitatively versus quantitatively distinct. Latent profile analysis identified four classes: (i) binge/purge (47%); (ii) non-fat-phobic low-weight (34%); (iii) fat-phobic low-weight (12%); and (iv) overweight disordered eating (6%). Taxometric analysis identified qualitative (categorical) distinctions between the binge/purge and non-fat-phobic low-weight classes, and also between the fat-phobic and non-fat-phobic low-weight classes. Distinctions between the fat-phobic low-weight and binge/purge classes were indeterminate. Empirically derived categories in Hong Kong showed recognizable correspondence with recognizable lifetime ED phenotypes. Although taxometric findings support two distinct classes of low weight EDs, LPA findings also support heterogeneity among non-fat-phobic individuals. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Differential transcriptomic responses of Biomphalaria glabrata (Gastropoda, Mollusca) to bacteria and metazoan parasites, Schistosoma mansoni and Echinostoma paraensei (Digenea, Platyhelminthes)

PubMed Central

Adema, Coen M; Hanington, Patrick C.; Lun, Cheng-Man; Rosenberg, George H.; Aragon, Anthony D; Stout, Barbara A; Richard, Mara L. Lennard; Gross, Paul S.; Loker, Eric S

2009-01-01

A 70-mer oligonucleotide-based microarray (1152 features) that emphasizes stress and immune responses factors was constructed to study transcriptomic responses of the snail Biomphalaria glabrata to different immune challenges. In addition to sequences with relevant putative ID and Gene Ontology (GO) annotation, the array features non-immune factors and unknown B. glabrata ESTs for functional gene discovery. The transcription profiles of B. glabrata (3 biological replicates, each a pool of 5 snails) were recorded at 12 hours post wounding, exposure to Gram negative or Gram positive bacteria (Escherichia coli and Micrococcus luteus, respectively), or infection with compatible trematode parasites (S. mansoni or E. paraensei, 20 miracidia/snail), relative to controls, using universal reference RNA. The data were subjected to Significance Analysis for Microarrays (SAM), with a false positive rate (FPR) ≤10%. Wounding yielded a modest differential expression profile (27 up/21 down) with affected features mostly dissimilar from other treatments. Partially overlapping, yet distinct expression profiles were recorded from snails challenged with E. coli (83 up/20 down) or M. luteus (120 up/42 down), mostly showing up-regulation of defense and stress-related features. Significantly altered expression of selected immune features indicates that B. glabrata detects and responds differently to compatible trematodes. Echinostoma paraensei infection was associated mostly with down regulation of many (immune-) transcripts (42 up/68 down), whereas S. mansoni exposure yielded a preponderance of up-regulated features (140 up/23 down), with only few known immune genes affected. These observations may reflect the divergent strategies developed by trematodes during their evolution as specialized pathogens of snails to negate host defense responses. Clearly, the immune defenses of B. glabrata distinguish and respond differently to various immune challenges. PMID:19962194

A comparison of honeybee (Apis mellifera) queen, worker and drone larvae by RNA-Seq.

PubMed

He, Xu-Jiang; Jiang, Wu-Jun; Zhou, Mi; Barron, Andrew B; Zeng, Zhi-Jiang

2017-11-06

Honeybees (Apis mellifera) have haplodiploid sex determination: males develop from unfertilized eggs and females develop from fertilized ones. The differences in larval food also determine the development of females. Here we compared the total somatic gene expression profiles of 2-day and 4-day-old drone, queen and worker larvae by RNA-Seq. The results from a co-expression network analysis on all expressed genes showed that 2-day-old drone and worker larvae were closer in gene expression profiles than 2-day-old queen larvae. This indicated that for young larvae (2-day-old) environmental factors such as larval diet have a greater effect on gene expression profiles than ploidy or sex determination. Drones had the most distinct gene expression profiles at the 4-day larval stage, suggesting that haploidy, or sex dramatically affects the gene expression of honeybee larvae. Drone larvae showed fewer differences in gene expression profiles at the 2-day and 4-day time points than the worker and queen larval comparisons (598 against 1190 and 1181), suggesting a different pattern of gene expression regulation during the larval development of haploid males compared to diploid females. This study indicates that early in development the queen caste has the most distinct gene expression profile, perhaps reflecting the very rapid growth and morphological specialization of this caste compared to workers and drones. Later in development the haploid male drones have the most distinct gene expression profile, perhaps reflecting the influence of ploidy or sex determination on gene expression. © 2017 Institute of Zoology, Chinese Academy of Sciences.

Soybean TCP transcription factors: Evolution, classification, protein interaction and stress and hormone responsiveness.

PubMed

Feng, Zhi-Juan; Xu, Sheng-Chun; Liu, Na; Zhang, Gu-Wen; Hu, Qi-Zan; Gong, Ya-Ming

2018-06-01

TEOSINTE-BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors, a family of plant-specific proteins, play crucial roles in plant growth and development and stress response. However, systematical information is unknown regarding the TCP gene family in soybean. In the present study, a total of 54 GmTCPs were identified in soybean, which were grouped into 11 groups with the typical TCP conserved domains. Phylogenetic relationship, protein motif and gene structure analyses distinguished the GmTCPs into two homology classes: Class I and Class II. Class II was then differentiated into two subclasses: CIN and CYC/TB1. Unique cis-element number and composition existed in the promoter regions which might be involved in the gene transcriptional regulation of different GmTCPs. Tissue expression analysis demonstrated the diverse spatiotemporal expression profiles of GmTCPs. Furthermore, the interaction protein of one previously functionally unknown TCP protein-GmTCP8 was investigated. Yeast two-hybrid assay showed the interaction between GmTCP8 and an abscisic acid receptor (GmPYL10). QRT-PCR assays indicated the distinct expression profiles of GmTCPs in response to abiotic stresses (heat, drought and salt) and stress-related signals (abscisic acid, brassinolide, salicylicacid and methyl jasmonate). These results will facilitate to uncover the possible roles of GmTCPs under abiotic stress and hormone signal responses in soybean. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Transcriptomics of coping strategies in free-swimming Lepeophtheirus salmonis (Copepoda) larvae responding to abiotic stress.

PubMed

Sutherland, Ben J G; Jantzen, Stuart G; Yasuike, Motoshige; Sanderson, Dan S; Koop, Ben F; Jones, Simon R M

2012-12-01

The salmon louse Lepeophtheirus salmonis is a marine ectoparasite of wild and farmed salmon in the Northern Hemisphere. Infections of farmed salmon are of economic and ecological concern. Nauplius and copepodid salmon lice larvae are free-swimming and disperse in the water column until they encounter a host. In this study, we characterized the sublethal stress responses of L. salmonis copepodid larvae by applying a 38K oligonucleotide microarray to profile transcriptomes following 24 h exposures to suboptimal salinity (30-10 parts per thousand (‰)) or temperature (16-4 °C) environments. Hyposalinity exposure resulted in large-scale gene expression changes relative to those elicited by a thermal gradient. Subsequently, transcriptome responses to a more finely resolved salinity gradient between 30 ‰ and 25 ‰ were profiled. Minimal changes occurred at 29 ‰ or 28 ‰, a threshold of response was identified at 27 ‰, and the largest response was at 25 ‰. Differentially expressed genes were clustered by pattern of expression, and clusters were characterized by functional enrichment analysis. Results indicate larval copepods adopt two distinct coping strategies in response to short-term hyposaline stress: a primary response using molecular chaperones and catabolic processes at 27 ‰; and a secondary response up-regulating ion pumps, transporters, a different suite of chaperones and apoptosis-related transcripts at 26 ‰ and 25 ‰. The results further our understanding of the tolerances of L. salmonis copepodids to salinity and temperature gradients and may assist in the development of salmon louse management strategies. © 2012 Blackwell Publishing Ltd.

Temporal Changes in Gene Expression after Injury in the Rat Retina

PubMed Central

Vázquez-Chona, Félix; Song, Bong K.; Geisert, Eldon E.

2010-01-01

Purpose The goal of this study was to define the temporal changes in gene expression after retinal injury and to relate these changes to the inflammatory and reactive response. A specific emphasis was placed on the tetraspanin family of proteins and their relationship with markers of reactive gliosis. Methods Retinal tears were induced in adult rats by scraping the retina with a needle. After different survival times (4 hours, and 1, 3, 7, and 30 days), the retinas were removed, and mRNA was isolated, prepared, and hybridized to the Affymatrix RGU34A microarray (Santa Clara, CA). Microarray results were confirmed by using RT-PCR and correlation to protein levels was determined. Results Of the 8750 genes analyzed, approximately 393 (4.5%) were differentially expressed. Clustering analysis revealed three major profiles: (1) The early response was characterized by the upregulation of transcription factors; (2) the delayed response included a high percentage of genes related to cell cycle and cell death; and (3) the late, sustained profile clustered a significant number of genes involved in retinal gliosis. The late, sustained cluster also contained the upregulated crystallin genes. The tetraspanins Cd9, Cd81, and Cd82 were also associated with the late, sustained response. Conclusions The use of microarray technology enables definition of complex genetic changes underlying distinct phases of the cellular response to retinal injury. The early response clusters genes associate with the transcriptional regulation of the wound-healing process and cell death. Most of the genes in the late, sustained response appear to be associated with reactive gliosis. PMID:15277499

Expression of three topologically distinct membrane proteins elicits unique stress response pathways in the yeast Saccharomyces cerevisiae.

PubMed

Buck, Teresa M; Jordan, Rick; Lyons-Weiler, James; Adelman, Joshua L; Needham, Patrick G; Kleyman, Thomas R; Brodsky, Jeffrey L

2015-06-01

Misfolded membrane proteins are retained in the endoplasmic reticulum (ER) and are subject to ER-associated degradation, which clears the secretory pathway of potentially toxic species. While the transcriptional response to environmental stressors has been extensively studied, limited data exist describing the cellular response to misfolded membrane proteins. To this end, we expressed and then compared the transcriptional profiles elicited by the synthesis of three ER retained, misfolded ion channels: The α-subunit of the epithelial sodium channel, ENaC, the cystic fibrosis transmembrane conductance regulator, CFTR, and an inwardly rectifying potassium channel, Kir2.1, which vary in their mass, membrane topologies, and quaternary structures. To examine transcriptional profiles in a null background, the proteins were expressed in yeast, which was previously used to examine the degradation requirements for each substrate. Surprisingly, the proteins failed to induce a canonical unfolded protein response or heat shock response, although messages encoding several cytosolic and ER lumenal protein folding factors rose when αENaC or CFTR was expressed. In contrast, the levels of these genes were unaltered by Kir2.1 expression; instead, the yeast iron regulon was activated. Nevertheless, a significant number of genes that respond to various environmental stressors were upregulated by all three substrates, and compared with previous microarray data we deduced the existence of a group of genes that reflect a novel misfolded membrane protein response. These data indicate that aberrant proteins in the ER elicit profound yet unique cellular responses. Copyright © 2015 the American Physiological Society.

Profiles of Reactivity in Cocaine-Exposed Children

ERIC Educational Resources Information Center

Schuetze, Pamela; Molnar, Danielle S.; Eiden, Rina D.

2012-01-01

This study explored the possibility that specific, theoretically consistent profiles of reactivity could be identified in a sample of cocaine-exposed infants and whether these profiles were associated with a range of infant and/or maternal characteristics. Cluster analysis was used to identify distinct groups of infants based on physiological,…

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

PubMed

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

2007-06-01

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

Clinical significance of early T-cell precursor acute lymphoblastic leukaemia: results of the Tokyo Children's Cancer Study Group Study L99-15.

PubMed

Inukai, Takeshi; Kiyokawa, Nobutaka; Campana, Dario; Coustan-Smith, Elaine; Kikuchi, Akira; Kobayashi, Miyuki; Takahashi, Hiroyuki; Koh, Katsuyoshi; Manabe, Atsushi; Kumagai, Masaaki; Ikuta, Koichiro; Hayashi, Yasuhide; Tsuchida, Masahiro; Sugita, Kanji; Ohara, Akira

2012-02-01

Early T-cell precursor acute lymphoblastic leukaemia (ETP-ALL) is a recently identified subtype of T-ALL with distinctive gene expression and cell marker profiles, poor response to chemotherapy and a very high risk of relapse. We determined the reliability of restricted panel of cell markers to identify EPT-ALL using a previously classified cohort. Then, we applied the cell marker profile that best discriminated ETP-ALL to a cohort of 91 patients with T-ALL enrolled in the Tokyo Children's Cancer Study Group L99-15 study, which included allogeneic stem cell transplantation (allo-SCT) for patients with poor prednisone response. Five of the 91 patients (5·5%) met the ETP-ALL criteria. There were no significant differences in presenting clinical features between these and the remaining 86 patients. Response to early remission induction therapy was inferior in ETP-ALL as compared with T-ALL. The ETP-ALL subgroup showed a significantly poorer event-free survival (4-year rate; 40%) than the T-ALL subgroup (70%, P=0·014). Of note, three of four relapsed ETP-ALL patients survived after allo-SCT, indicating that allo-SCT can be effective for this drug-resistant subtype of T-ALL. © 2011 Blackwell Publishing Ltd.

Identification of precision treatment strategies for relapsed/refractory multiple myeloma by functional drug sensitivity testing.

PubMed

Majumder, Muntasir Mamun; Silvennoinen, Raija; Anttila, Pekka; Tamborero, David; Eldfors, Samuli; Yadav, Bhagwan; Karjalainen, Riikka; Kuusanmäki, Heikki; Lievonen, Juha; Parsons, Alun; Suvela, Minna; Jantunen, Esa; Porkka, Kimmo; Heckman, Caroline A

2017-08-22

Novel agents have increased survival of multiple myeloma (MM) patients, however high-risk and relapsed/refractory patients remain challenging to treat and their outcome is poor. To identify novel therapies and aid treatment selection for MM, we assessed the ex vivo sensitivity of 50 MM patient samples to 308 approved and investigational drugs. With the results we i) classified patients based on their ex vivo drug response profile; ii) identified and matched potential drug candidates to recurrent cytogenetic alterations; and iii) correlated ex vivo drug sensitivity to patient outcome. Based on their drug sensitivity profiles, MM patients were stratified into four distinct subgroups with varied survival outcomes. Patients with progressive disease and poor survival clustered in a drug response group exhibiting high sensitivity to signal transduction inhibitors. Del(17p) positive samples were resistant to most drugs tested with the exception of histone deacetylase and BCL2 inhibitors. Samples positive for t(4;14) were highly sensitive to immunomodulatory drugs, proteasome inhibitors and several targeted drugs. Three patients treated based on the ex vivo results showed good response to the selected treatments. Our results demonstrate that ex vivo drug testing may potentially be applied to optimize treatment selection and achieve therapeutic benefit for relapsed/refractory MM.

Response profile of pheromone receptor neurons in male Grapholita molesta (Lepidoptera: Tortricidae).

PubMed

Ammagarahalli, Byrappa; Gemeno, César

2014-12-01

The response profile of olfactory receptor neurons (ORNs) of male Grapholita molesta (Busck) to the three female sex pheromone components [(Z)-8-dodecenyl acetate (Z8-12:Ac), (E)-8-dodecenyl acetate (E8-12:Ac), and (Z)-8-dodecenyl alcohol (Z8-12:OH)] was tested with single sensillum electrophysiology. Sensilla trichodea housed normally one, but sometimes two or three ORNs with distinct action potential amplitudes. One third of the sensilla contacted contained ORNs that were unresponsive to any of the pheromone components tested. The remaining sensilla contained one ORN that responded either to the major pheromone component, Z8-12:Ac ("Z-cells", 63.7% of sensilla), or to its isomer E8-12:Ac ("E-cells", 7.4% of sensilla). 31% of Z- and E-sensilla had 1 or 2 additional cells, but these did not respond to pheromone. None of the 176 sensilla contacted hosted ORNs that responded to Z8-12:OH. The proportion of Z- and E-cells on the antennae (100:11.6, respectively) is similar to the proportion of these compounds in the blend (100:6, respectively). The response of Z-cells was very specific, whereas E-cells also responded to the Z isomer, albeit with lower sensitivity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Profiles of Reactivity in Cocaine-Exposed Children

PubMed Central

Schuetze, Pamela; Molnar, Danielle S.; Eiden, Rina D.

2012-01-01

This study explored the possibility that specific, theoretically consistent profiles of reactivity could be identified in a sample of cocaine-exposed infants and whether these profiles were associated with a range of infant and/or maternal characteristics. Cluster analysis was used to identify distinct groups of infants based on physiological, behavioral and maternal reported measures of reactivity. Five replicable clusters were identified which corresponded to 1) Dysregulated/High Maternal Report Reactors, 2) Low Behavioral Reactors, 3) High Reactors, 4) Optimal Reactors and 5) Dysregulated/Low Maternal Report Reactors. These clusters were associated with differences in prenatal cocaine exposure status, birthweight, maternal depressive symptoms, and maternal negative affect during mother-infant interactions. These results support the presence of distinct reactivity profiles among high risk infants recruited on the basis of prenatal cocaine exposure and demographically similar control group infants not exposed to cocaine. PMID:23204615

More than apples and oranges - Detecting cancer with a fruit fly's antenna

NASA Astrophysics Data System (ADS)

Strauch, Martin; Lüdke, Alja; Münch, Daniel; Laudes, Thomas; Galizia, C. Giovanni; Martinelli, Eugenio; Lavra, Luca; Paolesse, Roberto; Ulivieri, Alessandra; Catini, Alexandro; Capuano, Rosamaria; di Natale, Corrado

2014-01-01

Cancer cells and non-cancer cells differ in their metabolism and they emit distinct volatile compound profiles, allowing to recognise cancer cells by their scent. Insect odorant receptors are excellent chemosensors with high sensitivity and a broad receptive range unmatched by current gas sensors. We thus investigated the potential of utilising the fruit fly's olfactory system to detect cancer cells. Using in vivo calcium imaging, we recorded an array of olfactory receptor neurons on the fruit fly's antenna. We performed multidimensional analysis of antenna responses, finding that cell volatiles from different cell types lead to characteristic response vectors. The distances between these response vectors are conserved across flies and can be used to discriminate healthy mammary epithelial cells from different types of breast cancer cells. This may expand the repertoire of clinical diagnostics, and it is the first step towards electronic noses equipped with biological sensors, integrating artificial and biological olfaction.

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

Sava Gallis, Dorina F.; Ermanoski, Ivan; Greathouse, Jeffrey A.

Here, we present a combined experimental and Grand Canonical Monte Carlo (GCMC) modeling study on the adsorption of iodine in three classes of nanoporous materials: activated charcoals, zeolites, and metal–organic frameworks (MOFs). Iodine adsorption profiles were measured for the first time in situ, with a uniquely designed sorption apparatus. It was determined that pore size and pore environment are responsible for a dynamic adsorption profile, correlated with distinct pressure ranges. At pressures below 0.3 atm, iodine adsorption is governed by a combination of small pores and extra-framework components (e.g., Ag+ ions in the zeolite mordenite). At regimes above 0.3 atm,more » the amount of iodine gas stored relates with an increase in pore size and specific surface area. GCMC results validate the trends noted experimentally and in addition provide a measure of the strength of the adsorbate–adsorbent interactions in these materials.« less

Measuring geographic segregation: a graph-based approach

NASA Astrophysics Data System (ADS)

Hong, Seong-Yun; Sadahiro, Yukio

2014-04-01

Residential segregation is a multidimensional phenomenon that encompasses several conceptually distinct aspects of geographical separation between populations. While various indices have been developed as a response to different definitions of segregation, the reliance on such single-figure indices could oversimplify the complex, multidimensional phenomena. In this regard, this paper suggests an alternative graph-based approach that provides more detailed information than simple indices: The concentration profile graphically conveys information about how evenly a population group is distributed over the study region, and the spatial proximity profile depicts the degree of clustering across different threshold levels. These graphs can also be summarized into single numbers for comparative purposes, but the interpretation can be more accurate by inspecting the additional information. To demonstrate the use of these methods, the residential patterns of three major ethnic groups in Auckland, namely Māori, Pacific peoples, and Asians, are examined using the 2006 census data.

Dynamic transcriptome profiling of Bean Common Mosaic Virus (BCMV) infection in Common Bean (Phaseolus vulgaris L.).

PubMed

Martin, Kathleen; Singh, Jugpreet; Hill, John H; Whitham, Steven A; Cannon, Steven B

2016-08-11

Bean common mosaic virus (BCMV) is widespread, with Phaseolus species as the primary host plants. Numerous BCMV strains have been identified on the basis of a panel of bean varieties that distinguish the pathogenicity types with respect to the viral strains. The molecular responses in Phaseolus to BCMV infection have not yet been well characterized. We report the transcriptional responses of a widely susceptible variety of common bean (Phaseolus vulgaris L., cultivar 'Stringless green refugee') to two BCMV strains, in a time-course experiment. We also report the genome sequence of a previously unreported BCMV strain. The interaction with the known strain NL1-Iowa causes moderate symptoms and large transcriptional responses, and the newly identified strain (Strain 2 or S2) causes severe symptoms and moderate transcriptional responses. The transcriptional profiles of host plants infected with the two isolates are distinct, and involve numerous differences in splice forms in particular genes, and pathway specific expression patterns. We identified differential host transcriptome response after infection of two different strains of Bean common mosaic virus (BCMV) in common bean (Phaseolus vulgaris L.). Virus infection initiated a suite of changes in gene expression level and patterns in the host plants. Pathways related to defense, gene regulation, metabolic processes, photosynthesis were specifically altered after virus infection. Results presented in this study can increase the understanding of host-pathogen interactions and provide resources for further investigations of the biological mechanisms in BCMV infection and defense.

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

PubMed

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

2015-08-10

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

Effectiveness of Nateglinide on In Vitro Insulin Secretion from Rat Pancreatic Islets Desensitized to Sulfonylureas

PubMed Central

Wang, Shuya; Dunning, Beth E.

2001-01-01

Chronic exposure of pancreatic islets to sulfonylureas (SUs) is known to impair the ability of islets to respond to subsequent acute stimulation by SUs or glucose. Nateglinide (NAT) is a novel insulinotropic agent with a primarily site of action at β-cell KATP channels, which is common to the structurally diverse drugs like repaglinide (REP) and the SUs. Earlier studies on the kinetics, glucosedependence and sensitivity to metabolic inhibitors of the interaction between NAT and KATP channels suggested a distinct signaling pathways with NAT compared to REP, glyburide (GLY) or glimepiride (GLI). To obtain further evidence for this concept, the present study compared the insulin secretion in vitro from rat islets stimulated acutely by NAT, GLY, GLI or REP at equipotent concentrations during 1-hr static incubation following overnight treatment with GLY or tolbutamide (TOL). The islets fully retained the responsiveness to NAT stimulation after prolonged pretreatment with both SUs, while their acute response to REP, GLY, and GLI was markedly attenuated, confirming the desensitization of islets. The insulinotropic efficacy of NAT in islets desensitized to SUs may result from a distinct receptor/effector mechanism, which contributes to the unique pharmacological profile of NAT. PMID:12369729

Novel Therapeutics for Multiple Sclerosis Designed by Parasitic Worms.

PubMed

Dixit, Aakanksha; Tanaka, Akane; Greer, Judith M; Donnelly, Sheila

2017-10-13

The evolutionary response to endemic infections with parasitic worms (helminth) was the development of a distinct regulatory immune profile arising from the need to encapsulate the helminths while simultaneously repairing tissue damage. According to the old friend's hypothesis, the diminished exposure to these parasites in the developed world has resulted in a dysregulated immune response that contributes to the increased incidence of immune mediated diseases such as Multiple Sclerosis (MS). Indeed, the global distribution of MS shows an inverse correlation to the prevalence of helminth infection. On this basis, the possibility of treating MS with helminth infection has been explored in animal models and phase 1 and 2 human clinical trials. However, the possibility also exists that the individual immune modulatory molecules secreted by helminth parasites may offer a more defined therapeutic strategy.

Genome-wide analysis and expression profiling of the Solanum tuberosum aquaporins.

PubMed

Venkatesh, Jelli; Yu, Jae-Woong; Park, Se Won

2013-12-01

Aquaporins belongs to the major intrinsic proteins involved in the transcellular membrane transport of water and other small solutes. A comprehensive genome-wide search for the homologues of Solanum tuberosum major intrinsic protein (MIP) revealed 41 full-length potato aquaporin genes. All potato aquaporins are grouped into five subfamilies; plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs), NOD26-like intrinsic proteins (NIPs), small basic intrinsic proteins (SIPs) and x-intrinsic proteins (XIPs). Functional predictions based on the aromatic/arginine (ar/R) selectivity filters and Froger's positions showed a remarkable difference in substrate transport specificity among subfamilies. The expression pattern of potato aquaporins, examined by qPCR analysis, showed distinct expression profiles in various organs and tuber developmental stages. Furthermore, qPCR analysis of potato plantlets, subjected to various abiotic stresses revealed the marked effect of stresses on expression levels of aquaporins. Taken together, the expression profiles of aquaporins imply that aquaporins play important roles in plant growth and development, in addition to maintaining water homeostasis in response to environmental stresses. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Evidence for a supermassive black hole in the nucleus of the Seyfert galaxy NGC 5548

NASA Technical Reports Server (NTRS)

Crenshaw, D. Michael; Blackwell, James H., Jr.

1990-01-01

The international campaign to monitor the variable Seyfert 1 galaxy NGC 5548 with the IUE has provided an extensive and well-sampled set of spectroscopic observations. These observations are used to study the response of the C IV 1550 A emission-line profile to changes in the photoionizing continuum. Near the end of the IUE campaign, the continuum flux at 1440 A and the total C IV flux dopped by factors of 2.9 and 1.8, respectively, in 16 days. The red wing of the C IV profile responded more rapidly to the sharp continuum drop than the blue wing, indicating that clouds in the inner broad-line region (BLR) are undergoing gravitational infall. These results provide direct evidence that the central engine is a supermassive object, presumably a black hole, with a mass on the order of 10 to the 7th solar masses. Analysis of the profile variations also demonstrates that excess emission in the blue wing of C IV is from a component that is physically distinct from the bulk of the BLR.

Differences in the refractory properties of two distinct inhibitory circuitries in field CA1 of the hippocampus.

PubMed

Arai, A; Silberg, J; Lynch, G

1995-12-18

Extracellular reflections of IPSPs were examined in two distinct circuitries in field CA1 of the hippocampus. Stimulation in the stratum radiatum in the presence of AMPA receptor antagonists elicited positive potentials in the same stratum that were eliminated by picrotoxin, a blocker of GABAA receptors. Laminar profile analysis revealed that the response was maximal in the stratum radiatum at a point well distal to the pyramidal cell body layer and had a negative reflection in the stratum oriens. These field IPSPs presumably mediate the feedforward inhibition normally activated by the Schaffer-commissural projections to field CA1. Stimulation of the alveus produced an antidromic response followed by a much slower positive potential in recordings collected in the pyramidal cell layer. The latter response was suppressed by AMPA receptor antagonists or picrotoxin, as expected for disynaptic, recurrent (feedback) inhibition. The laminar profile for the feedback field IPSPs had its maximum near the pyramidal cell layer and its negative dipole in the stratum radiatum. Feedforward IPSPs were inhibited by about 50% if they were preceded within 200 ms by a priming pulse while feedback IPSPs were reduced by less than 20% under comparable conditions. The refractory effect was minimally dependent on stimulation intensity but was strongly affected by an antagonist of GABAB receptors. Attempts to modify IPSPs in the s. radiatum with long trains of low frequency stimulation or with theta-burst stimulation were not successful, suggesting that GABAergic synapses do not have the plasticities found in their glutamatergic counterparts. These results indicate that interneurons contacted by the extrinsic afferents of hippocampus form GABAergic synapses that differ in terms of spatial location and functional properties from the synapses generated by interneurons innervated by the recurrent collaterals of the pyramidal cells. The findings also suggest that repetitive afferent activity, while reducing the influence of dendritic IPSPs on excitatory input, will leave feedback suppression of cell spiking largely intact.

Molecular and Photosynthetic Responses to Prolonged Darkness and Subsequent Acclimation to Re-Illumination in the Diatom Phaeodactylum tricornutum

PubMed Central

Nymark, Marianne; Valle, Kristin C.; Hancke, Kasper; Winge, Per; Andresen, Kjersti; Johnsen, Geir; Bones, Atle M.; Brembu, Tore

2013-01-01

Photosynthetic diatoms that live suspended throughout the water column will constantly be swept up and down by vertical mixing. When returned to the photic zone after experiencing longer periods in darkness, mechanisms exist that enable the diatoms both to survive sudden light exposure and immediately utilize the available energy in photosynthesis and growth. We have investigated both the response to prolonged darkness and the re-acclimation to moderate intensity white irradiance (E = 100 µmol m−2 s−1) in the diatom Phaeodactylum tricornutum, using an integrated approach involving global transcriptional profiling, pigment analyses, imaging and photo-physiological measurements. The responses were studied during continuous white light, after 48 h of dark treatment and after 0.5 h, 6 h, and 24 h of re-exposure to the initial irradiance. The analyses resulted in several intriguing findings. Dark treatment of the cells led to 1) significantly decreased nuclear transcriptional activity, 2) distinct intracellular changes, 3) fixed ratios of the light-harvesting pigments despite a decrease in the total cell pigment pool, and 4) only a minor drop in photosynthetic efficiency (ΦPSII_max). Re-introduction of the cells to the initial light conditions revealed 5) distinct expression profiles for nuclear genes involved in photosynthesis and those involved in photoprotection, 6) rapid rise in photosynthetic parameters (α and rETRmax) within 0.5 h of re-exposure to light despite a very modest de novo synthesis of photosynthetic compounds, and 7) increasingly efficient resonance energy transfer from fucoxanthin chlorophyll a/c-binding protein complexes to photosystem II reaction centers during the first 0.5 h, supporting the observations stated in 6). In summary, the results show that despite extensive transcriptional, metabolic and intracellular changes, the ability of cells to perform photosynthesis was kept intact during the length of the experiment. We conclude that P. tricornutum maintains a functional photosynthetic apparatus during dark periods that enables prompt recovery upon re-illumination. PMID:23520530

Strings on a Violin: Location Dependence of Frequency Tuning in Active Dendrites.

PubMed

Das, Anindita; Rathour, Rahul K; Narayanan, Rishikesh

2017-01-01

Strings on a violin are tuned to generate distinct sound frequencies in a manner that is firmly dependent on finger location along the fingerboard. Sound frequencies emerging from different violins could be very different based on their architecture, the nature of strings and their tuning. Analogously, active neuronal dendrites, dendrites endowed with active channel conductances, are tuned to distinct input frequencies in a manner that is dependent on the dendritic location of the synaptic inputs. Further, disparate channel expression profiles and differences in morphological characteristics could result in dendrites on different neurons of the same subtype tuned to distinct frequency ranges. Alternately, similar location-dependence along dendritic structures could be achieved through disparate combinations of channel profiles and morphological characteristics, leading to degeneracy in active dendritic spectral tuning. Akin to strings on a violin being tuned to different frequencies than those on a viola or a cello, different neuronal subtypes exhibit distinct channel profiles and disparate morphological characteristics endowing each neuronal subtype with unique location-dependent frequency selectivity. Finally, similar to the tunability of musical instruments to elicit distinct location-dependent sounds, neuronal frequency selectivity and its location-dependence are tunable through activity-dependent plasticity of ion channels and morphology. In this morceau, we explore the origins of neuronal frequency selectivity, and survey the literature on the mechanisms behind the emergence of location-dependence in distinct forms of frequency tuning. As a coda to this composition, we present some future directions for this exciting convergence of biophysical mechanisms that endow a neuron with frequency multiplexing capabilities.

Early experiences mediate distinct adult gene expression and reproductive programs in Caenorhabditis elegans

PubMed Central

Ow, Maria C.; Nichitean, Alexandra M.; Dorus, Steve; Hall, Sarah E.

2018-01-01

Environmental stress during early development in animals can have profound effects on adult phenotypes via programmed changes in gene expression. Using the nematode C. elegans, we demonstrated previously that adults retain a cellular memory of their developmental experience that is manifested by differences in gene expression and life history traits; however, the sophistication of this system in response to different environmental stresses, and how it dictates phenotypic plasticity in adults that contribute to increased fitness in response to distinct environmental challenges, was unknown. Using transcriptional profiling, we show here that C. elegans adults indeed retain distinct cellular memories of different environmental conditions. We identified approximately 500 genes in adults that entered dauer due to starvation that exhibit significant opposite (“seesaw”) transcriptional phenotypes compared to adults that entered dauer due to crowding, and are distinct from animals that bypassed dauer. Moreover, we show that two-thirds of the genes in the genome experience a 2-fold or greater seesaw trend in gene expression, and based upon the direction of change, are enriched in large, tightly linked regions on different chromosomes. Importantly, these transcriptional programs correspond to significant changes in brood size depending on the experienced stress. In addition, we demonstrate that while the observed seesaw gene expression changes occur in both somatic and germline tissue, only starvation-induced changes require a functional GLP-4 protein necessary for germline development, and both programs require the Argonaute CSR-1. Thus, our results suggest that signaling between the soma and the germ line can generate phenotypic plasticity as a result of early environmental experience, and likely contribute to increased fitness in adverse conditions and the evolution of the C. elegans genome. PMID:29447162

Rhinovirus infection induces distinct transcriptome profiles in polarized human macrophages.

PubMed

Rajput, Charu; Walsh, Megan P; Eder, Breanna N; Metitiri, Ediri E; Popova, Antonia P; Hershenson, Marc B

2018-05-01

Infections with rhinovirus (RV) cause asthma exacerbations. Recent studies suggest that macrophages play a role in asthmatic airway inflammation and the innate immune response to RV infection. Macrophages exhibit phenotypes based on surface markers and gene expression. We hypothesized that macrophage polarization state alters gene expression in response to RV infection. Cells were derived from human peripheral blood derived monocytes. M1 and M2 polarization was carried out by using IFN-γ and IL-4, respectively, and RNA was extracted for Affymetrix Human Gene ST2.1 exon arrays. Selected genes were validated by quantitative (q)PCR. Treatment of nonactivated (M0) macrophages with IFN-γ and IL-4 induced the expression of 252 and 153 distinct genes, respectively, including previously-identified M1 and M2 markers. RV infection of M0 macrophages induced upregulation of 232 genes; pathway analysis showed significant overrepresentation of genes involved in IFN-α/β signaling and cytokine signaling in the immune system. RV infection induced differential expression of 195 distinct genes in M1-like macrophages but only seven distinct genes in M2-like-polarized cells. In a secondary analysis, comparison between M0-, RV-infected, and M1-like-polarized, RV-infected macrophages revealed differential expression of 227 genes including those associated with asthma and its exacerbation. qPCR demonstrated increased expression of CCL8, CXCL10, TNFSF10, TNFSF18, IL6, NOD2, and GSDMD and reduced expression of VNN1, AGO1, and AGO2. Together, these data show that, in contrast to M2-like-polarized macrophages, gene expression of M1-like macrophages is highly regulated by RV.

Near-surface structure of the Central Scandinavian Caledonides in northern Trøndelag, Norway, from correlation of seismic and MT profiles using gravity and magnetic data

NASA Astrophysics Data System (ADS)

Ebbing, J.; Goerigk, L.; Nasuti, A.; Roberts, D.; Korja, T. J.; Smirnov, M.

2014-12-01

The deep geology of northern Trøndelag is somewhat speculative as the Central Scandinavian Caledonides are intersected by the Møre-Trøndelag Fault Complex (MTFC) and only a few depth-penetrating geophysical profiles exist. Here, we correlate the mapped geological units and faults between a seismic-reflection profile and a MT profile. The seismic-reflection data were acquired in 5 segments over the period 1986-1990. The westernmost section of the seismic profile is dominated by a complex pattern of reflections and diffractions. This type of pattern is typical of polydeformed terranes with a mixture of contrasting felsic and mafic lithologies. The two steeply-dipping strands of the MTFC (Hitra-Snåsa and Verran faults) that transect the profile do not show any distinctive signature in the seismic data. The MT data were acquired in 2007 from the Swedish border to the Norwegian coast. The conductivity profile shows some distinct vertical changes as well as changes from the near-surface to shallow depths. The strands of the MTFC show especially a distinctive change in conductivity. The two profiles are almost parallel but separated by 100 km. To correlate the structures seen on both profiles, we have applied lineament analysis and 3D modelling of the gravity and magnetic field. The tilt derivative of the magnetic and isostatic gravity anomaly clearly allows us to identify and link the main geological boundaries between the profiles and to trace the strands of the MTFC from one profile to the other. This trend analysis indicates that at least the Verran Fault visibly modifies the pattern of seismic reflections. However, the main change in crustal lithology occurs farther to the west, almost at the coast where the Tarva Fault intersects the MT profile. This integrated analysis shows the benefit of combining gravity and magnetic interpretations with MT and seismic data to enable us to understand the near-surface geology and structure in more detail.

Implicit Theories of Ability, Epistemic Beliefs, and Academic Motivation: A Person-Centered Approach

ERIC Educational Resources Information Center

Chen, Jason

2010-01-01

The purpose of the present study was to (1) explore which distinct student profiles emerge from measures of science epistemic beliefs and implicit theories of science ability; (2) investigate how these emergent student profiles relate to science motivation and achievement; and (3) explore how these emergent student profiles differ by…

Creating Rich Portraits: A Mixed-Methods Approach to Understanding Profiles of Intrinsic and Extrinsic Motivations

ERIC Educational Resources Information Center

Corpus, Jennifer Henderlong; Wormington, Stephanie V.; Haimovitz, Kyla

2016-01-01

A person-centered, mixed-methods approach (self-report surveys, semistructured interviews, school records) was used to characterize and evaluate profiles of intrinsic and extrinsic motivations among 243 third- through eighth-grade students. Cluster analysis suggested four distinct profiles: high quantity (high intrinsic, high extrinsic), primarily…

Distinct gene regulatory programs define the inhibitory effects of liver X receptors and PPARG on cancer cell proliferation.

PubMed

Savic, Daniel; Ramaker, Ryne C; Roberts, Brian S; Dean, Emma C; Burwell, Todd C; Meadows, Sarah K; Cooper, Sara J; Garabedian, Michael J; Gertz, Jason; Myers, Richard M

2016-07-11

The liver X receptors (LXRs, NR1H2 and NR1H3) and peroxisome proliferator-activated receptor gamma (PPARG, NR1C3) nuclear receptor transcription factors (TFs) are master regulators of energy homeostasis. Intriguingly, recent studies suggest that these metabolic regulators also impact tumor cell proliferation. However, a comprehensive temporal molecular characterization of the LXR and PPARG gene regulatory responses in tumor cells is still lacking. To better define the underlying molecular processes governing the genetic control of cellular growth in response to extracellular metabolic signals, we performed a comprehensive, genome-wide characterization of the temporal regulatory cascades mediated by LXR and PPARG signaling in HT29 colorectal cancer cells. For this analysis, we applied a multi-tiered approach that incorporated cellular phenotypic assays, gene expression profiles, chromatin state dynamics, and nuclear receptor binding patterns. Our results illustrate that the activation of both nuclear receptors inhibited cell proliferation and further decreased glutathione levels, consistent with increased cellular oxidative stress. Despite a common metabolic reprogramming, the gene regulatory network programs initiated by these nuclear receptors were widely distinct. PPARG generated a rapid and short-term response while maintaining a gene activator role. By contrast, LXR signaling was prolonged, with initial, predominantly activating functions that transitioned to repressive gene regulatory activities at late time points. Through the use of a multi-tiered strategy that integrated various genomic datasets, our data illustrate that distinct gene regulatory programs elicit common phenotypic effects, highlighting the complexity of the genome. These results further provide a detailed molecular map of metabolic reprogramming in cancer cells through LXR and PPARG activation. As ligand-inducible TFs, these nuclear receptors can potentially serve as attractive therapeutic targets for the treatment of various cancers.

Heterogeneity in Neutrophil Microparticles Reveals Distinct Proteome and Functional Properties*

PubMed Central

Dalli, Jesmond; Montero-Melendez, Trinidad; Norling, Lucy V; Yin, Xiaoke; Hinds, Charles; Haskard, Dorian; Mayr, Manuel; Perretti, Mauro

2013-01-01

Altered plasma neutrophil microparticle levels have recently been implicated in a number of vascular and inflammatory diseases, yet our understanding of their actions is very limited. Herein, we investigate the proteome of neutrophil microparticles in order to shed light on their biological actions. Stimulation of human neutrophils, either in suspension or adherent to an endothelial monolayer, led to the production of microparticles containing >400 distinct proteins with only 223 being shared by the two subsets. For instance, postadherent microparticles were enriched in alpha-2 macroglobulin and ceruloplasmin, whereas microparticles produced by neutrophils in suspension were abundant in heat shock 70 kDa protein 1. Annexin A1 and lactotransferrin were expressed in both microparticle subsets. We next determined relative abundance of these proteins in three types of human microparticle samples: healthy volunteer plasma, plasma of septic patients and skin blister exudates finding that these proteins were differentially expressed on neutrophil microparticles from these samples reflecting in part the expression profiles we found in vitro. Functional assessment of the neutrophil microparticles subsets demonstrated that in response to direct stimulation neutrophil microparticles produced reactive oxygen species and leukotriene B4 as well as locomoted toward a chemotactic gradient. Finally, we investigated the actions of the two neutrophil microparticles subsets described herein on target cell responses. Microarray analysis with human primary endothelial cells incubated with either microparticle subset revealed a discrete modulation of endothelial cell gene expression profile. These findings demonstrate that neutrophil microparticles are heterogenous and can deliver packaged information propagating the activation status of the parent cell, potentially exerting novel and fundamental roles both under homeostatic and disease conditions. PMID:23660474

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

PubMed

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

2017-07-01

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

Genome-wide analysis of alternative splicing during dendritic cell response to a bacterial challenge.

PubMed

Rodrigues, Raquel; Grosso, Ana Rita; Moita, Luís

2013-01-01

The immune system relies on the plasticity of its components to produce appropriate responses to frequent environmental challenges. Dendritic cells (DCs) are critical initiators of innate immunity and orchestrate the later and more specific adaptive immunity. The generation of diversity in transcriptional programs is central for effective immune responses. Alternative splicing is widely considered a key generator of transcriptional and proteomic complexity, but its role has been rarely addressed systematically in immune cells. Here we used splicing-sensitive arrays to assess genome-wide gene- and exon-level expression profiles in human DCs in response to a bacterial challenge. We find widespread alternative splicing events and splicing factor transcriptional signatures induced by an E. coli challenge to human DCs. Alternative splicing acts in concert with transcriptional modulation, but these two mechanisms of gene regulation affect primarily distinct functional gene groups. Alternative splicing is likely to have an important role in DC immunobiology because it affects genes known to be involved in DC development, endocytosis, antigen presentation and cell cycle arrest.

White Adipose Tissue Is a Reservoir for Memory T Cells and Promotes Protective Memory Responses to Infection.

PubMed

Han, Seong-Ji; Glatman Zaretsky, Arielle; Andrade-Oliveira, Vinicius; Collins, Nicholas; Dzutsev, Amiran; Shaik, Jahangheer; Morais da Fonseca, Denise; Harrison, Oliver J; Tamoutounour, Samira; Byrd, Allyson L; Smelkinson, Margery; Bouladoux, Nicolas; Bliska, James B; Brenchley, Jason M; Brodsky, Igor E; Belkaid, Yasmine

2017-12-19

White adipose tissue bridges body organs and plays a fundamental role in host metabolism. To what extent adipose tissue also contributes to immune surveillance and long-term protective defense remains largely unknown. Here, we have shown that at steady state, white adipose tissue contained abundant memory lymphocyte populations. After infection, white adipose tissue accumulated large numbers of pathogen-specific memory T cells, including tissue-resident cells. Memory T cells in white adipose tissue expressed a distinct metabolic profile, and white adipose tissue from previously infected mice was sufficient to protect uninfected mice from lethal pathogen challenge. Induction of recall responses within white adipose tissue was associated with the collapse of lipid metabolism in favor of antimicrobial responses. Our results suggest that white adipose tissue represents a memory T cell reservoir that provides potent and rapid effector memory responses, positioning this compartment as a potential major contributor to immunological memory. Published by Elsevier Inc.

Linear and conformation specific antibodies in aged beagles after prolonged vaccination with aggregated Abeta

PubMed Central

Vasilevko, Vitaly; Pop, Viorela; Kim, Hyun Jin; Saing, Tommy; Glabe, Charles C.; Milton, Saskia; Barrett, Edward G.; Cotman, Carl W.; Cribbs, David H.; Head, Elizabeth

2010-01-01

Previously we showed that anti-Aβ peptide immunotherapy significantly attenuated Alzheimer’s-like amyloid deposition in the central nervous system of aged canines. In this report we have characterized the changes that occurred in the humoral immune response over 2.4 years in canines immunized repeatedly with aggregated Aβ1–42 (AN1792) formulated in alum adjuvant. We observed a rapid and robust induction of anti-Aβ antibody titers, which were associated with an anti-inflammatory T helper type 2 (Th2) response. The initial antibody response was against dominant linear epitope at the N-terminus region of the Aβ1–42 peptide, which is identical to the one in humans and vervet monkeys. After multiple immunizations the antibody response drifted toward the elevation of antibodies that recognized conformational epitopes of assembled forms of Aβ and other types of amyloid. Our findings indicate that prolonged immunization results in distinctive temporal changes in antibody profiles, which may be important for other experimental and clinical settings. PMID:20451612

Phase response curves for models of earthquake fault dynamics

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

Franović, Igor, E-mail: franovic@ipb.ac.rs; Kostić, Srdjan; Perc, Matjaž

We systematically study effects of external perturbations on models describing earthquake fault dynamics. The latter are based on the framework of the Burridge-Knopoff spring-block system, including the cases of a simple mono-block fault, as well as the paradigmatic complex faults made up of two identical or distinct blocks. The blocks exhibit relaxation oscillations, which are representative for the stick-slip behavior typical for earthquake dynamics. Our analysis is carried out by determining the phase response curves of first and second order. For a mono-block fault, we consider the impact of a single and two successive pulse perturbations, further demonstrating how themore » profile of phase response curves depends on the fault parameters. For a homogeneous two-block fault, our focus is on the scenario where each of the blocks is influenced by a single pulse, whereas for heterogeneous faults, we analyze how the response of the system depends on whether the stimulus is applied to the block having a shorter or a longer oscillation period.« less

Tiled Microarray Identification of Novel Viral Transcript Structures and Distinct Transcriptional Profiles during Two Modes of Productive Murine Gammaherpesvirus 68 Infection

PubMed Central

Cheng, Benson Yee Hin; Zhi, Jizu; Santana, Alexis; Khan, Sohail; Salinas, Eduardo; Forrest, J. Craig; Zheng, Yueting; Jaggi, Shirin; Leatherwood, Janet

2012-01-01

We applied a custom tiled microarray to examine murine gammaherpesvirus 68 (MHV68) polyadenylated transcript expression in a time course of de novo infection of fibroblast cells and following phorbol ester-mediated reactivation from a latently infected B cell line. During de novo infection, all open reading frames (ORFs) were transcribed and clustered into four major temporal groups that were overlapping yet distinct from clusters based on the phorbol ester-stimulated B cell reactivation time course. High-density transcript analysis at 2-h intervals during de novo infection mapped gene boundaries with a 20-nucleotide resolution, including a previously undefined ORF73 transcript and the MHV68 ORF63 homolog of Kaposi's sarcoma-associated herpesvirus vNLRP1. ORF6 transcript initiation was mapped by tiled array and confirmed by 5′ rapid amplification of cDNA ends. The ∼1.3-kb region upstream of ORF6 was responsive to lytic infection and MHV68 RTA, identifying a novel RTA-responsive promoter. Transcription in intergenic regions consistent with the previously defined expressed genomic regions was detected during both types of productive infection. We conclude that the MHV68 transcriptome is dynamic and distinct during de novo fibroblast infection and upon phorbol ester-stimulated B cell reactivation, highlighting the need to evaluate further transcript structure and the context-dependent molecular events that govern viral gene expression during chronic infection. PMID:22318145

Current source density correlates of cerebellar Golgi and Purkinje cell responses to tactile input

PubMed Central

Tahon, Koen; Wijnants, Mike; De Schutter, Erik

2011-01-01

The overall circuitry of the cerebellar cortex has been known for over a century, but the function of many synaptic connections remains poorly characterized in vivo. We used a one-dimensional multielectrode probe to estimate the current source density (CSD) of Crus IIa in response to perioral tactile stimuli in anesthetized rats and to correlate current sinks and sources to changes in the spike rate of corecorded Golgi and Purkinje cells. The punctate stimuli evoked two distinct early waves of excitation (at <10 and ∼20 ms) associated with current sinks in the granular layer. The second wave was putatively of corticopontine origin, and its associated sink was located higher in the granular layer than the first trigeminal sink. The distinctive patterns of granular-layer sinks correlated with the spike responses of corecorded Golgi cells. In general, Golgi cell spike responses could be linearly reconstructed from the CSD profile. A dip in simple-spike activity of coregistered Purkinje cells correlated with a current source deep in the molecular layer, probably generated by basket cell synapses, interspersed between sparse early sinks presumably generated by synapses from granule cells. The late (>30 ms) enhancement of simple-spike activity in Purkinje cells was characterized by the absence of simultaneous sinks in the granular layer and by the suppression of corecorded Golgi cell activity, pointing at inhibition of Golgi cells by Purkinje axon collaterals as a likely mechanism of late Purkinje cell excitation. PMID:21228303

Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network.

PubMed

Keegan, Caroline; Krutzik, Stephan; Schenk, Mirjam; Scumpia, Philip O; Lu, Jing; Pang, Yan Ling Joy; Russell, Brandon S; Lim, Kok Seong; Shell, Scarlet; Prestwich, Erin; Su, Dan; Elashoff, David; Hershberg, Robert M; Bloom, Barry R; Belisle, John T; Fortune, Sarah; Dedon, Peter C; Pellegrini, Matteo; Modlin, Robert L

2018-05-01

Upon recognition of a microbial pathogen, the innate and adaptive immune systems are linked to generate a cell-mediated immune response against the foreign invader. The culture filtrate of Mycobacterium tuberculosis contains ligands, such as M. tuberculosis tRNA, that activate the innate immune response and secreted Ags recognized by T cells to drive adaptive immune responses. In this study, bioinformatics analysis of gene-expression profiles derived from human PBMCs treated with distinct microbial ligands identified a mycobacterial tRNA-induced innate immune network resulting in the robust production of IL-12p70, a cytokine required to instruct an adaptive Th1 response for host defense against intracellular bacteria. As validated by functional studies, this pathway contained a feed-forward loop, whereby the early production of IL-18, type I IFNs, and IL-12p70 primed NK cells to respond to IL-18 and produce IFN-γ, enhancing further production of IL-12p70. Mechanistically, tRNA activates TLR3 and TLR8, and this synergistic induction of IL-12p70 was recapitulated by the addition of a specific TLR8 agonist with a TLR3 ligand to PBMCs. These data indicate that M. tuberculosis tRNA activates a gene network involving the integration of multiple innate signals, including types I and II IFNs, as well as distinct cell types to induce IL-12p70. Copyright © 2018 by The American Association of Immunologists, Inc.

Longitudinal Analyses of Expressive Language Development Reveal Two Distinct Language Profiles among Young Children with Autism Spectrum Disorders

PubMed Central

Tek, Saime; Mesite, Laura; Fein, Deborah; Naigles, Letitia

2013-01-01

Although children with ASD show significant variation in language skills, research on what type(s) of language profiles they demonstrate has been limited. Using growth-curve analyses, we investigated how different groups of young children with ASD show increases in the size of their lexicon, morpho-syntactic production as measured by Brown’s 14 grammatical morphemes, and wh-question complexity, compared to TD children, across six time points. Children with ASD who had higher verbal skills were comparable to TD children on most language measures, whereas the children with ASD who had low verbal skills had flatter trajectories in most language measures. Thus, two distinct language profiles emerged for children with ASD. PMID:23719855

Nasal Airway Microbiota Profile and Severe Bronchiolitis in Infants: A Case-control Study.

PubMed

Hasegawa, Kohei; Linnemann, Rachel W; Mansbach, Jonathan M; Ajami, Nadim J; Espinola, Janice A; Petrosino, Joseph F; Piedra, Pedro A; Stevenson, Michelle D; Sullivan, Ashley F; Thompson, Amy D; Camargo, Carlos A

2017-11-01

Little is known about the relationship of airway microbiota with bronchiolitis in infants. We aimed to identify nasal airway microbiota profiles and to determine their association with the likelihood of bronchiolitis in infants. A case-control study was conducted. As a part of a multicenter prospective study, we collected nasal airway samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 110 age-matched healthy controls. By applying 16S ribosomal RNA gene sequencing and an unbiased clustering approach to these 150 nasal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis. Overall, the median age was 3 months and 56% were male. Unbiased clustering of airway microbiota identified 4 distinct profiles: Moraxella-dominant profile (37%), Corynebacterium/Dolosigranulum-dominant profile (27%), Staphylococcus-dominant profile (15%) and mixed profile (20%). Proportion of bronchiolitis was lowest in infants with Moraxella-dominant profile (14%) and highest in those with Staphylococcus-dominant profile (57%), corresponding to an odds ratio of 7.80 (95% confidence interval, 2.64-24.9; P < 0.001). In the multivariable model, the association between Staphylococcus-dominant profile and greater likelihood of bronchiolitis persisted (odds ratio for comparison with Moraxella-dominant profile, 5.16; 95% confidence interval, 1.26-22.9; P = 0.03). By contrast, Corynebacterium/Dolosigranulum-dominant profile group had low proportion of infants with bronchiolitis (17%); the likelihood of bronchiolitis in this group did not significantly differ from those with Moraxella-dominant profile in both unadjusted and adjusted analyses. In this case-control study, we identified 4 distinct nasal airway microbiota profiles in infants. Moraxella-dominant and Corynebacterium/Dolosigranulum-dominant profiles were associated with low likelihood of bronchiolitis, while Staphylococcus-dominant profile was associated with high likelihood of bronchiolitis.

Multidimensionality of behavioural phenotypes in Atlantic cod, Gadus morhua.

PubMed

Meager, Justin J; Fernö, Anders; Skjæraasen, Jon Egil; Järvi, Torbjörn; Rodewald, Petra; Sverdrup, Gisle; Winberg, Svante; Mayer, Ian

2012-06-25

Much of the inter-individual variation observed in animal behaviour is now attributed to the existence of behavioural phenotypes or animal personalities. Such phenotypes may be fundamental to fisheries and aquaculture, yet there have been few detailed studies of this phenomenon in exploited marine animals. We investigated the behavioural and neuroendocrine responses of Atlantic cod (Gadus morhua L.), to situations reflecting critical ecological challenges: predator attacks and territorial challenges. Both hatchery-reared and wild fish were tested and behavioural profiles were compared with baseline conditions. We then used an objective, multivariate approach, rather than assigning individuals along one-dimensional behavioural axes, to examine whether distinct behavioural phenotypes were present. Our results indicate that two distinct behavioural phenotypes were evident in fish from each background. In hatchery-reared fish, phenotypes displayed divergent locomotor activity, sheltering, brain monoamine concentrations and responses to competitive challenges. In wild fish, phenotypes were distinguished primarily by locomotor activity, sheltering and responsiveness to predator stimuli. Hatcheries presumably represent a more stressful social environment, and social behaviour and neuroendocrine responses were important in discerning behavioural phenotypes in hatchery fish, whereas antipredator responses were important in discerning phenotypes in wild fish that have previously encountered predators. In both fish types, behavioural and physiological traits that classified individuals into phenotypes were not the same as those that were correlated across situations. These results highlight the multidimensionality of animal personalities, and that the processes that regulate one suite of behavioural traits may be very different to the processes that regulate other behaviours. Copyright © 2012 Elsevier Inc. All rights reserved.

Examination of emotion-induced changes in eating: A latent profile analysis of the Emotional Appetite Questionnaire.

PubMed

Bourdier, L; Morvan, Y; Kotbagi, G; Kern, L; Romo, L; Berthoz, S

2018-04-01

It is now recognized that emotions can influence food intake. While some people report eating less when distressed, others report either no change of eating or eating more in the same condition. The question whether this interindividual variability also occurs in response to positive emotions has been overlooked in most studies on Emotional Eating (EE). Using the Emotional Appetite Questionnaire (EMAQ) and Latent Profile Analysis, this study aimed to examine the existence of latent emotion-induced changes in eating profiles, and explore how these profiles differ by testing their relations with 1) age and sex, 2) BMI and risk for eating disorders (ED) and 3) factors that are known to be associated with EE such as perceived positive/negative feelings, depression, anxiety, stress symptoms and impulsivity. Among 401 university students (245 females) who completed the EMAQ, 3 profiles emerged (P1:11.2%, P2:60.1%, P3:28.7%), with distinct patterns of eating behaviors in response to negative emotions and situations but few differences regarding positive ones. Negative emotional overeaters (P1) and negative emotional undereaters (P3) reported similar levels of emotional distress and positive feelings, and were at greater risk for ED. However, the people in the former profile i) reported decreasing their food intake in a positive context, ii) were in majority females, iii) had higher BMI and iv) were more prone to report acting rashly when experiencing negative emotions. Our findings suggest that a person-centred analysis of the EMAQ scores offers a promising way to capture the inter-individual variability of emotionally-driven eating behaviors. These observations also add to the growing literature underscoring the importance of further investigating the role of different facets of impulsivity in triggering overeating and to develop more targeted interventions of EE. Copyright © 2017 Elsevier Ltd. All rights reserved.

Complex modulation of the Aedes aegypti transcriptome in response to dengue virus infection.

PubMed

Bonizzoni, Mariangela; Dunn, W Augustine; Campbell, Corey L; Olson, Ken E; Marinotti, Osvaldo; James, Anthony A

2012-01-01

Dengue fever is the most important arboviral disease world-wide, with Aedes aegypti being the major vector. Interactions between the mosquito host and dengue viruses (DENV) are complex and vector competence varies among geographically-distinct Ae. aegypti populations. Additionally, dengue is caused by four antigenically-distinct viral serotypes (DENV1-4), each with multiple genotypes. Each virus genotype interacts differently with vertebrate and invertebrate hosts. Analyses of alterations in mosquito transcriptional profiles during DENV infection are expected to provide the basis for identifying networks of genes involved in responses to viruses and contribute to the molecular-genetic understanding of vector competence. In addition, this knowledge is anticipated to support the development of novel disease-control strategies. RNA-seq technology was used to assess genome-wide changes in transcript abundance at 1, 4 and 14 days following DENV2 infection in carcasses, midguts and salivary glands of the Ae. aegypti Chetumal strain. DENV2 affected the expression of 397 Ae. aegypti genes, most of which were down-regulated by viral infection. Differential accumulation of transcripts was mainly tissue- and time-specific. Comparisons of our data with other published reports reveal conservation of functional classes, but limited concordance of specific mosquito genes responsive to DENV2 infection. These results indicate the necessity of additional studies of mosquito-DENV interactions, specifically those focused on recently-derived mosquito strains with multiple dengue virus serotypes and genotypes.

Delineation of Stenotrophomonas maltophilia isolates from cystic fibrosis patients by fatty acid methyl ester profiles and matrix-assisted laser desorption/ionization time-of-flight mass spectra using hierarchical cluster analysis and principal component analysis.

PubMed

Vidigal, Pedrina Gonçalves; Mosel, Frank; Koehling, Hedda Luise; Mueller, Karl Dieter; Buer, Jan; Rath, Peter Michael; Steinmann, Joerg

2014-12-01

Stenotrophomonas maltophilia is an opportunist multidrug-resistant pathogen that causes a wide range of nosocomial infections. Various cystic fibrosis (CF) centres have reported an increasing prevalence of S. maltophilia colonization/infection among patients with this disease. The purpose of this study was to assess specific fingerprints of S. maltophilia isolates from CF patients (n = 71) by investigating fatty acid methyl esters (FAMEs) through gas chromatography (GC) and highly abundant proteins by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and to compare them with isolates obtained from intensive care unit (ICU) patients (n = 20) and the environment (n = 11). Principal component analysis (PCA) of GC-FAME patterns did not reveal a clustering corresponding to distinct CF, ICU or environmental types. Based on the peak area index, it was observed that S. maltophilia isolates from CF patients produced significantly higher amounts of fatty acids in comparison with ICU patients and the environmental isolates. Hierarchical cluster analysis (HCA) based on the MALDI-TOF MS peak profiles of S. maltophilia revealed the presence of five large clusters, suggesting a high phenotypic diversity. Although HCA of MALDI-TOF mass spectra did not result in distinct clusters predominantly composed of CF isolates, PCA revealed the presence of a distinct cluster composed of S. maltophilia isolates from CF patients. Our data suggest that S. maltophilia colonizing CF patients tend to modify not only their fatty acid patterns but also their protein patterns as a response to adaptation in the unfavourable environment of the CF lung. © 2014 The Authors.

Variability of O3 and NO2 profile shapes during DISCOVER-AQ: Implications for satellite observations and comparisons to model-simulated profiles

NASA Astrophysics Data System (ADS)

Flynn, Clare Marie; Pickering, Kenneth E.; Crawford, James H.; Weinheimer, Andrew J.; Diskin, Glenn; Thornhill, K. Lee; Loughner, Christopher; Lee, Pius; Strode, Sarah A.

2016-12-01

To investigate the variability of in situ profile shapes under a variety of meteorological and pollution conditions, results are presented of an agglomerative hierarchical cluster analysis of the in situ O3 and NO2 profiles for each of the four campaigns of the NASA DISCOVER-AQ mission. Understanding the observed profile variability for these trace gases is useful for understanding the accuracy of the assumed profile shapes used in satellite retrieval algorithms as well as for understanding the correlation between satellite column observations and surface concentrations. The four campaigns of the DISCOVER-AQ mission took place in Maryland during July 2011, the San Joaquin Valley of California during January-February 2013, the Houston, Texas, metropolitan region during September 2013, and the Denver-Front Range region of Colorado during July-August 2014. Several distinct profile clusters emerged for the California, Texas, and Colorado campaigns for O3, indicating significant variability of O3 profile shapes, while the Maryland campaign presented only one distinct O3 cluster. In contrast, very few distinct profile clusters emerged for NO2 during any campaign for this particular clustering technique, indicating the NO2 profile behavior was relatively uniform throughout each campaign. However, changes in NO2 profile shape were evident as the boundary layer evolved through the day, but they were apparently not significant enough to yield more clusters. The degree of vertical mixing (as indicated by temperature lapse rate) associated with each cluster exerted an important influence on the shapes of the median cluster profiles for O3, as well as impacted the correlations between the associated column and surface data for each cluster for O3. The correlation analyses suggest satellites may have the best chance to relate to surface O3 under the conditions encountered during the Maryland campaign Clusters 1 and 2, which include deep, convective boundary layers and few interruptions to this connection from complex meteorology, chemical environments, or orography. The regional CMAQ model captured the shape factors for O3, and moderately well captured the NO2 shape factors, for the conditions associated with the Maryland campaign, suggesting that a regional air quality model may adequately specify a priori profile shapes for remote sensing retrievals. CMAQ shape factor profiles were not as well represented for the other regions.

Systematic analysis of Ca2+ homeostasis in Saccharomyces cerevisiae based on chemical-genetic interaction profiles

PubMed Central

Ghanegolmohammadi, Farzan; Yoshida, Mitsunori; Ohnuki, Shinsuke; Sukegawa, Yuko; Okada, Hiroki; Obara, Keisuke; Kihara, Akio; Suzuki, Kuninori; Kojima, Tetsuya; Yachie, Nozomu; Hirata, Dai; Ohya, Yoshikazu

2017-01-01

We investigated the global landscape of Ca2+ homeostasis in budding yeast based on high-dimensional chemical-genetic interaction profiles. The morphological responses of 62 Ca2+-sensitive (cls) mutants were quantitatively analyzed with the image processing program CalMorph after exposure to a high concentration of Ca2+. After a generalized linear model was applied, an analysis of covariance model was used to detect significant Ca2+–cls interactions. We found that high-dimensional, morphological Ca2+–cls interactions were mixed with positive (86%) and negative (14%) chemical-genetic interactions, whereas one-dimensional fitness Ca2+–cls interactions were all negative in principle. Clustering analysis with the interaction profiles revealed nine distinct gene groups, six of which were functionally associated. In addition, characterization of Ca2+–cls interactions revealed that morphology-based negative interactions are unique signatures of sensitized cellular processes and pathways. Principal component analysis was used to discriminate between suppression and enhancement of the Ca2+-sensitive phenotypes triggered by inactivation of calcineurin, a Ca2+-dependent phosphatase. Finally, similarity of the interaction profiles was used to reveal a connected network among the Ca2+ homeostasis units acting in different cellular compartments. Our analyses of high-dimensional chemical-genetic interaction profiles provide novel insights into the intracellular network of yeast Ca2+ homeostasis. PMID:28566553

Identifying the Dominant Personality Profiles in Medical Students: Implications for Their Well-Being and Resilience.

PubMed

Eley, Diann S; Leung, Janni; Hong, Barry A; Cloninger, Kevin M; Cloninger, C Robert

2016-01-01

There is a high prevalence of stress, depression, and burn-out in medical students. Medical students differ widely in personality traits, self-perceptions, and values that may have an impact on their well-being. This study aimed to investigate variability in their personality profiles in relation to their potential for well-being and resilience. Participants were 808 medical students from The University of Queensland. An online questionnaire collected socio-demographics and the Temperament and Character Inventory to assess personality traits. Latent profile analyses identified students' trait profiles. Two distinct personality profiles were identified. Profile 1 ("Resilient") characterized 60% of the sample and was distinguished by low Harm Avoidance combined with very high Persistence, Self-Directedness and Cooperativeness compared to Profile 2 ("Conscientious"). Both Profiles had average levels of Reward Dependence and Novelty Seeking and low levels of Self-Transcendence. Profiles did not differ by age, gender, or country of birth, but rural background students were more likely to have Profile 1. While both Profiles indicate mature and healthy personalities, the combination of traits in Profile 1 is more strongly indicative of well-being and resilience. Finding two distinct profiles of personality highlights the importance of considering combinations of traits and how they may interact with medical students' potential for well-being. Although both profiles of students show healthy personalities, many may lack the resilience to maintain well-being over years of medical training. Programs that develop character and personality self-awareness would enhance their well-being and prepare them to promote the health of their patients.

Identifying the Dominant Personality Profiles in Medical Students: Implications for Their Well-Being and Resilience

PubMed Central

Leung, Janni; Hong, Barry A.; Cloninger, Kevin M.; Cloninger, C. Robert

2016-01-01

Purpose There is a high prevalence of stress, depression, and burn-out in medical students. Medical students differ widely in personality traits, self-perceptions, and values that may have an impact on their well-being. This study aimed to investigate variability in their personality profiles in relation to their potential for well-being and resilience. Method Participants were 808 medical students from The University of Queensland. An online questionnaire collected socio-demographics and the Temperament and Character Inventory to assess personality traits. Latent profile analyses identified students’ trait profiles. Results Two distinct personality profiles were identified. Profile 1 (“Resilient”) characterized 60% of the sample and was distinguished by low Harm Avoidance combined with very high Persistence, Self-Directedness and Cooperativeness compared to Profile 2 ("Conscientious"). Both Profiles had average levels of Reward Dependence and Novelty Seeking and low levels of Self-Transcendence. Profiles did not differ by age, gender, or country of birth, but rural background students were more likely to have Profile 1. While both Profiles indicate mature and healthy personalities, the combination of traits in Profile 1 is more strongly indicative of well-being and resilience. Conclusions Finding two distinct profiles of personality highlights the importance of considering combinations of traits and how they may interact with medical students’ potential for well-being. Although both profiles of students show healthy personalities, many may lack the resilience to maintain well-being over years of medical training. Programs that develop character and personality self-awareness would enhance their well-being and prepare them to promote the health of their patients. PMID:27494401

Distinct gene expression profiles determine molecular treatment response in childhood acute lymphoblastic leukemia.

PubMed

Cario, Gunnar; Stanulla, Martin; Fine, Bernard M; Teuffel, Oliver; Neuhoff, Nils V; Schrauder, André; Flohr, Thomas; Schäfer, Beat W; Bartram, Claus R; Welte, Karl; Schlegelberger, Brigitte; Schrappe, Martin

2005-01-15

Treatment resistance, as indicated by the presence of high levels of minimal residual disease (MRD) after induction therapy and induction consolidation, is associated with a poor prognosis in childhood acute lymphoblastic leukemia (ALL). We hypothesized that treatment resistance is an intrinsic feature of ALL cells reflected in the gene expression pattern and that resistance to chemotherapy can be predicted before treatment. To test these hypotheses, gene expression signatures of ALL samples with high MRD load were compared with those of samples without measurable MRD during treatment. We identified 54 genes that clearly distinguished resistant from sensitive ALL samples. Genes with low expression in resistant samples were predominantly associated with cell-cycle progression and apoptosis, suggesting that impaired cell proliferation and apoptosis are involved in treatment resistance. Prediction analysis using randomly selected samples as a training set and the remaining samples as a test set revealed an accuracy of 84%. We conclude that resistance to chemotherapy seems at least in part to be an intrinsic feature of ALL cells. Because treatment response could be predicted with high accuracy, gene expression profiling could become a clinically relevant tool for treatment stratification in the early course of childhood ALL.

Hard x-ray response of a CdZnTe ring-drift detector

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

Owens, A.; Hartog, R. den; Quarati, F.

We present the results of an experimental study of a special type of CdZnTe detector of hard x and {gamma} rays--A-drift detector. The device consists of a double ring electrode structure surrounding a central point anode with a guard plane surrounding the outer anode ring. The detector can be operated in two distinctively different modes of charge collection--pseudohemispherical and pseudodrift. We study the detector response profiles obtained by scanning the focused x-ray beam over the whole detector area, specifically the variations in count rate, peak position, and energy resolution for x rays from 10 to 100 keV. In addition, atmore » 662 keV the energy resolution was shown to be 4.8 keV, more than a factor of 2 better than for CdZnTe coplanar grid detectors. To interpret the experimental data, we derive an analytical expression for the spatial distribution of the electric field inside the detector and neglecting carrier diffusion, and identify carrier collection patterns for both modes of operation within the drift model approximation. We show that this model provides a good understanding of measured profiles.« less

A Real Time Chemotaxis Assay Unveils Unique Migratory Profiles amongst Different Primary Murine Macrophages

PubMed Central

Iqbal, Asif J.; Regan-Komito, Daniel; Christou, Ivy; White, Gemma E.; McNeill, Eileen; Kenyon, Amy; Taylor, Lewis; Kapellos, Theodore S.; Fisher, Edward A.; Channon, Keith M.; Greaves, David R.

2013-01-01

Chemotaxis assays are an invaluable tool for studying the biological activity of inflammatory mediators such as CC chemokines, which have been implicated in a wide range of chronic inflammatory diseases. Conventional chemotaxis systems such as the modified Boyden chamber are limited in terms of the data captured given that the assays are analysed at a single time-point. We report the optimisation and validation of a label-free, real-time cell migration assay based on electrical cell impedance to measure chemotaxis of different primary murine macrophage populations in response to a range of CC chemokines and other chemoattractant signalling molecules. We clearly demonstrate key differences in the migratory behavior of different murine macrophage populations and show that this dynamic system measures true macrophage chemotaxis rather than chemokinesis or fugetaxis. We highlight an absolute requirement for Gαi signaling and actin cytoskeletal rearrangement as demonstrated by Pertussis toxin and cytochalasin D inhibition. We also studied the chemotaxis of CD14+ human monocytes and demonstrate distinct chemotactic profiles amongst different monocyte donors to CCL2. This real-time chemotaxis assay will allow a detailed analysis of factors that regulate macrophage responses to chemoattractant cytokines and inflammatory mediators. PMID:23516549

Profiles of More and Less Successful L2 Learners: A Cluster Analysis Study

ERIC Educational Resources Information Center

Sparks, Richard L.; Patton, Jon; Ganschow, Leonore

2012-01-01

This retrospective study examined L1 achievement, intelligence, L2 aptitude, and L2 proficiency profiles of 208 students completing two years of high school L2 courses. A cluster analysis was performed to determine whether distinct cognitive and achievement profiles of more and less successful L2 learners would emerge. The results of…

Empirically Based Phenotypic Profiles of Children with Pervasive Developmental Disorders: Interpretation in the Light of the DSM-5

ERIC Educational Resources Information Center

Greaves-Lord, Kirstin; Eussen, Mart L. J. M.; Verhulst, Frank C.; Minderaa, Ruud B.; Mandy, William; Hudziak, James J.; Steenhuis, Mark Peter; de Nijs, Pieter F.; Hartman, Catharina A.

2013-01-01

This study aimed to contribute to the Diagnostic and Statistical Manual (DSM) debates on the conceptualization of autism by investigating (1) whether empirically based distinct phenotypic profiles could be distinguished within a sample of mainly cognitively able children with pervasive developmental disorder (PDD), and (2) how profiles related to…

Development of a Typology of Dual-Earner Couples Caring for Children and Aging Parents

ERIC Educational Resources Information Center

Cullen, Jennifer C.; Hammer, Leslie B.; Neal, Margaret B.; Sinclair, Robert R.

2009-01-01

Using a national sample of 267 couples, the authors identify distinct profiles of dual-earner couples in the sandwiched generation (i.e., those caring for children and aging parents) using cluster analysis and then assess the relationship between these profiles and work-family conflict. The profiles are defined by characteristics of couples' child…

What Is Successful Writing? An Investigation into the Multiple Ways Writers Can Write Successful Essays

ERIC Educational Resources Information Center

Crossley, Scott A.; Roscoe, Rod; McNamara, Danielle S.

2014-01-01

This study identifies multiple profiles of successful essays via a cluster analysis approach using linguistic features reported by a variety of natural language processing tools. The findings from the study indicate that there are four profiles of successful writers for the samples analyzed. These four profiles are linguistically distinct from one…

Developing Coping Typologies of Minority Adolescents: A Latent Profile Analysis

ERIC Educational Resources Information Center

Aldridge, Arianna A.; Roesch, Scott C.

2008-01-01

Latent profile analysis (LPA) was used to develop a coping typology of minority adolescents (M = 15.5 years). A multiethnic sample (n = 354) was recruited from a program aimed at serving low-income students. LPA revealed three distinct coping profiles. The first comprised adolescents who used a number of specific coping strategies at a low level…

Psychological Type Profile of Canadian Baptist Youth Leaders: Implications for Christian Education

ERIC Educational Resources Information Center

Francis, Leslie J.; Fawcett, Bruce; Linkletter, Jody; Robbins, Mandy; Stairs, Dale

2016-01-01

A recent study of the psychological type profile of Christian youth workers in the UK drew attention to differences between the profiles of youth workers and clergy, and highlighted distinctive strengths and weaknesses that may be experienced by youth workers in Christian ministry. The present study, employing the Francis Psychological Type Scales…

Differences in performance and learning proficiency on the Wisconsin Card Sorting Test in schizophrenia: do they reflect distinct neurocognitive subtypes with distinct functional profiles?

PubMed

Kurtz, Matthew M; Wexler, Bruce E

2006-01-31

The aim of this study was two-fold: 1) to determine whether a priori subtyping of patients with schizophrenia based on both overall performance on a measure of executive-function, the Wisconsin Card Sorting Test (WCST), and ability to learn the task with expanded instruction, could be confirmed with other, independent measures of executive-function and learning, and, if so, 2) to determine whether these groups have different neurocognitive profiles and show differences in functional capacity. Fifty-four outpatients with schizophrenia were divided by WCST performance into three groups: intact executive-function (n=28), "good learner" (n=13), and "poor learner" (n=13) groups. These groups were then assessed with a comprehensive neurocognitive test battery and a performance-based measure of functional status, the UCSD Performance-based Skills Assessment (UPSA). The WCST-intact subgroup performed significantly better than other groups on a second measure of executive-function and in working memory, and speeded motor sequencing. Impaired WCST patients who benefited from expanded WCST instruction ("good learners") also showed better performance than patients who did not benefit from instruction ("poor-learners") on a second measure of learning, as well as on a measure of auditory divided attention. The intact WCST subgroup had greater functional capacity than either "strong" or "poor" learners. These subtypes may have implications for response to behavioral treatment interventions.

Proteomics and Deep Sequencing Comparison of Seasonally Active Venom Glands in the Platypus Reveals Novel Venom Peptides and Distinct Expression Profiles*

PubMed Central

Wong, Emily S. W.; Morgenstern, David; Mofiz, Ehtesham; Gombert, Sara; Morris, Katrina M.; Temple-Smith, Peter; Renfree, Marilyn B.; Whittington, Camilla M.; King, Glenn F.; Warren, Wesley C.; Papenfuss, Anthony T.; Belov, Katherine

2012-01-01

The platypus is a venomous monotreme. Male platypuses possess a spur on their hind legs that is connected to glands in the pelvic region. They produce venom only during the breeding season, presumably to fight off conspecifics. We have taken advantage of this unique seasonal production of venom to compare the transcriptomes of in- and out-of-season venom glands, in conjunction with proteomic analysis, to identify previously undiscovered venom genes. Comparison of the venom glands revealed distinct gene expression profiles that are consistent with changes in venom gland morphology and venom volumes in and out of the breeding season. Venom proteins were identified through shot-gun sequenced venom proteomes of three animals using RNA-seq-derived transcripts for peptide-spectral matching. 5,157 genes were expressed in the venom glands, 1,821 genes were up-regulated in the in-season gland, and 10 proteins were identified in the venom. New classes of platypus-venom proteins identified included antimicrobials, amide oxidase, serpin protease inhibitor, proteins associated with the mammalian stress response pathway, cytokines, and other immune molecules. Five putative toxins have only been identified in platypus venom: growth differentiation factor 15, nucleobindin-2, CD55, a CXC-chemokine, and corticotropin-releasing factor-binding protein. These novel venom proteins have potential biomedical and therapeutic applications and provide insights into venom evolution. PMID:22899769

Proteomics and deep sequencing comparison of seasonally active venom glands in the platypus reveals novel venom peptides and distinct expression profiles.

PubMed

Wong, Emily S W; Morgenstern, David; Mofiz, Ehtesham; Gombert, Sara; Morris, Katrina M; Temple-Smith, Peter; Renfree, Marilyn B; Whittington, Camilla M; King, Glenn F; Warren, Wesley C; Papenfuss, Anthony T; Belov, Katherine

2012-11-01

The platypus is a venomous monotreme. Male platypuses possess a spur on their hind legs that is connected to glands in the pelvic region. They produce venom only during the breeding season, presumably to fight off conspecifics. We have taken advantage of this unique seasonal production of venom to compare the transcriptomes of in- and out-of-season venom glands, in conjunction with proteomic analysis, to identify previously undiscovered venom genes. Comparison of the venom glands revealed distinct gene expression profiles that are consistent with changes in venom gland morphology and venom volumes in and out of the breeding season. Venom proteins were identified through shot-gun sequenced venom proteomes of three animals using RNA-seq-derived transcripts for peptide-spectral matching. 5,157 genes were expressed in the venom glands, 1,821 genes were up-regulated in the in-season gland, and 10 proteins were identified in the venom. New classes of platypus-venom proteins identified included antimicrobials, amide oxidase, serpin protease inhibitor, proteins associated with the mammalian stress response pathway, cytokines, and other immune molecules. Five putative toxins have only been identified in platypus venom: growth differentiation factor 15, nucleobindin-2, CD55, a CXC-chemokine, and corticotropin-releasing factor-binding protein. These novel venom proteins have potential biomedical and therapeutic applications and provide insights into venom evolution.

Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by gene-expression profiling in synovia

PubMed Central

Lequerré, Thierry; Bansard, Carine; Vittecoq, Olivier; Derambure, Céline; Hiron, Martine; Daveau, Maryvonne; Tron, François; Ayral, Xavier; Biga, Norman; Auquit-Auckbur, Isabelle; Chiocchia, Gilles; Le Loët, Xavier; Salier, Jean-Philippe

2009-01-01

Introduction Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia. Methods Synovial biopsies were obtained by arthroscopy from 15 patients (4 early untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions). Extracted mRNAs were used for large-scale gene-expression profiling. The different gene-expression combinations identified by comparison of profiles of early, LS RA and healthy synovia were linked to the biological processes involved in each situation. Results Three combinations of 719, 116 and 52 transcripts discriminated, respectively, early from LS RA, and early or LS RA from healthy synovia. We identified several gene clusters and distinct molecular signatures specifically expressed during early or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA. Conclusions Early and LS RA have distinct molecular signatures with different biological processes participating at different times during the course of the disease. These results suggest that better knowledge of the main biological processes involved at a given RA stage might help to choose the most appropriate treatment. PMID:19563633

Transcriptomic Analysis of Lung Tissue from Cigarette Smoke-Induced Emphysema Murine Models and Human Chronic Obstructive Pulmonary Disease Show Shared and Distinct Pathways.

PubMed

Yun, Jeong H; Morrow, Jarrett; Owen, Caroline A; Qiu, Weiliang; Glass, Kimberly; Lao, Taotao; Jiang, Zhiqiang; Perrella, Mark A; Silverman, Edwin K; Zhou, Xiaobo; Hersh, Craig P

2017-07-01

Although cigarette smoke (CS) is the primary risk factor for chronic obstructive pulmonary disease (COPD), the underlying molecular mechanisms for the significant variability in developing COPD in response to CS are incompletely understood. We performed lung gene expression profiling of two different wild-type murine strains (C57BL/6 and NZW/LacJ) and two genetic models with mutations in COPD genome-wide association study genes (HHIP and FAM13A) after 6 months of chronic CS exposure and compared the results to human COPD lung tissues. We identified gene expression patterns that correlate with severity of emphysema in murine and human lungs. Xenobiotic metabolism and nuclear erythroid 2-related factor 2-mediated oxidative stress response were commonly regulated molecular response patterns in C57BL/6, Hhip +/- , and Fam13a -/- murine strains exposed chronically to CS. The CS-resistant Fam13a -/- mouse and NZW/LacJ strain revealed gene expression response pattern differences. The Fam13a -/- strain diverged in gene expression compared with C57BL/6 control only after CS exposure. However, the NZW/LacJ strain had a unique baseline expression pattern, enriched for nuclear erythroid 2-related factor 2-mediated oxidative stress response and xenobiotic metabolism, and converged to a gene expression pattern similar to the more susceptible wild-type C57BL/6 after CS exposure. These results suggest that distinct molecular pathways may account for resistance to emphysema. Surprisingly, there were few genes commonly modulated in mice and humans. Our study suggests that gene expression responses to CS may be largely species and model dependent, yet shared pathways could provide biologically significant insights underlying individual susceptibility to CS.

The Fecal Microbiota Profile and Bronchiolitis in Infants

PubMed Central

Linnemann, Rachel W.; Mansbach, Jonathan M.; Ajami, Nadim J.; Espinola, Janice A.; Petrosino, Joseph F.; Piedra, Pedro A.; Stevenson, Michelle D.; Sullivan, Ashley F.; Thompson, Amy D.; Camargo, Carlos A.

2016-01-01

BACKGROUND: Little is known about the association of gut microbiota, a potentially modifiable factor, with bronchiolitis in infants. We aimed to determine the association of fecal microbiota with bronchiolitis in infants. METHODS: We conducted a case–control study. As a part of multicenter prospective study, we collected stool samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 115 age-matched healthy controls. By applying 16S rRNA gene sequencing and an unbiased clustering approach to these 155 fecal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis. RESULTS: Overall, the median age was 3 months, 55% were male, and 54% were non-Hispanic white. Unbiased clustering of fecal microbiota identified 4 distinct profiles: Escherichia-dominant profile (30%), Bifidobacterium-dominant profile (21%), Enterobacter/Veillonella-dominant profile (22%), and Bacteroides-dominant profile (28%). The proportion of bronchiolitis was lowest in infants with the Enterobacter/Veillonella-dominant profile (15%) and highest in the Bacteroides-dominant profile (44%), corresponding to an odds ratio of 4.59 (95% confidence interval, 1.58–15.5; P = .008). In the multivariable model, the significant association between the Bacteroides-dominant profile and a greater likelihood of bronchiolitis persisted (odds ratio for comparison with the Enterobacter/Veillonella-dominant profile, 4.24; 95% confidence interval, 1.56–12.0; P = .005). In contrast, the likelihood of bronchiolitis in infants with the Escherichia-dominant or Bifidobacterium-dominant profile was not significantly different compared with those with the Enterobacter/Veillonella-dominant profile. CONCLUSIONS: In this case–control study, we identified 4 distinct fecal microbiota profiles in infants. The Bacteroides-dominant profile was associated with a higher likelihood of bronchiolitis. PMID:27354456

Multiple layers of heterogeneity and subset diversity in human MAIT cell responses to distinct microorganisms and to innate cytokines.

PubMed

Dias, Joana; Leeansyah, Edwin; Sandberg, Johan K

2017-07-03

Mucosa-associated invariant T (MAIT) cells are a large innate-like T-cell subset in humans defined by invariant TCR Vα7.2 use and expression of CD161. MAIT cells recognize microbial riboflavin metabolites of bacterial or fungal origin presented by the monomorphic MR1 molecule. The extraordinary level of evolutionary conservation of MR1 and the limited known diversity of riboflavin metabolite antigens have suggested that MAIT cells are relatively homogeneous and uniform in responses against diverse microbes carrying the riboflavin biosynthesis pathway. The ability of MAIT cells to exhibit microbe-specific functional specialization has not been thoroughly investigated. Here, we found that MAIT cell responses against Escherichia coli and Candida albicans displayed microbe-specific polyfunctional response profiles, antigen sensitivity, and response magnitudes. MAIT cell effector responses against E. coli and C. albicans displayed differential MR1 dependency and TCR β-chain bias, consistent with possible divergent antigen subspecificities between these bacterial and fungal organisms. Finally, although the MAIT cell immunoproteome was overall relatively homogenous and consistent with an effector memory-like profile, it still revealed diversity in a set of natural killer cell-associated receptors. Among these, CD56, CD84, and CD94 defined a subset with higher expression of the transcription factors promyelocytic leukemia zinc finger (PLZF), eomesodermin, and T-bet and enhanced capacity to respond to IL-12 and IL-18 stimulation. Thus, the conserved and innate-like MAIT cells harbor multiple layers of functional heterogeneity as they respond to bacterial or fungal organisms or innate cytokines and adapt their antimicrobial response patterns in a stimulus-specific manner.

Mass spectrometry-based metabolic profiling of gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cells.

PubMed

Fujimura, Yoshinori; Ikenaga, Naoki; Ohuchida, Kenoki; Setoyama, Daiki; Irie, Miho; Miura, Daisuke; Wariishi, Hiroyuki; Murata, Masaharu; Mizumoto, Kazuhiro; Hashizume, Makoto; Tanaka, Masao

2014-03-01

Gemcitabine resistance (GR) is one of the critical issues for therapy for pancreatic cancer, but the mechanism still remains unclear. Our aim was to increase the understanding of GR by metabolic profiling approach. To establish GR cells, 2 human pancreatic cancer cell lines, SUIT-2 and CAPAN-1, were exposed to increasing concentration of gemcitabine. Both parental and chemoresistant cells obtained by this treatment were subjected to metabolic profiling based on liquid chromatography-mass spectrometry. Multivariate statistical analyses, both principal component analysis and orthogonal partial least squares discriminant analysis, distinguished metabolic signature of responsiveness and resistance to gemcitabine in both SUIT-2 and CAPAN-1 cells. Among significantly different (P < 0.005) metabolite peaks between parental and GR cells, we identified metabolites related to several metabolic pathways such as amino acid, nucleotide, energy, cofactor, and vitamin pathways. Decreases in glutamine and proline levels as well as increases in aspartate, hydroxyproline, creatine, and creatinine levels were observed in chemoresistant cells from both cell lines. These results suggest that metabolic profiling can isolate distinct features of pancreatic cancer in the metabolome of gemcitabine-sensitive and GR cells. These findings may contribute to the biomarker discovery and an enhanced understanding of GR in pancreatic cancer.

Paraneoplastic myasthenia gravis: immunological and clinical aspects.

PubMed

Skeie, G O; Romi, F

2008-10-01

Paraneoplastic myasthenia gravis (MG) is accompanied by a neoplasm, usually thymoma. In patients with thymoma and a specific genetic make-up, the paraneoplastic immune response develops further in thymic remnant or peripheral lymphatic tissue. Paraneoplastic MG and late-onset MG (age >or= 50 years) share a similar immunological profile with high titin and ryanodine receptor (RyR) antibody prevalence. This profile is the most important predictor of clinical outcome in paraneoplastic MG. The presence of a thymoma per se does not cause more severe MG. MG severity is linked to the patient's immunological profile. Paraneoplastic MG causes a distinctive non-limb symptom profile at MG onset, characterized by bulbar, ocular, neck, and respiratory symptoms. When the diagnosis of paraneoplastic MG is established, the neoplasm should be removed surgically. Pre-thymectomy plasmapheresis or iv-IgG should be considered in these patients to minimize post-thymectomy MG exacerbation risk. Paraneoplastic MG usually continues after thymectomy. The pharmacological treatment of paraneoplastic MG does not differ from non-paraneoplastic MG, except for tacrolimus that should be considered in difficult cases. Tacrolimus is an immunosuppressant acting specifically in RyR antibody positive patients through enhancing RyR-related sarcoplasmic calcium release that in theory might be blocked by RyR antibodies, causing symptomatic relief in paraneoplastic MG.

Dynamic non-reciprocal meta-surfaces with arbitrary phase reconfigurability based on photonic transition in meta-atoms

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

Shi, Yu; Fan, Shanhui, E-mail: shanhui@stanford.edu

2016-01-11

We introduce a distinct class of dynamic non-reciprocal meta-surfaces with arbitrary phase-reconfigurability. This meta-surface consists of an array of meta-atoms, each of which is subject to temporal refractive index modulation, which induces photonic transitions between the states of the meta-atom. We show that arbitrary phase profile for the outgoing wave can be achieved by controlling the phase of the modulation at each meta-atom. Moreover, such dynamic meta-surfaces exhibit non-reciprocal response without the need for magneto-optical effects. The use of photonic transition significantly enhances the tunability and the possible functionalities of meta-surfaces.

Yeast Modulation of Human Dendritic Cell Cytokine Secretion: An In Vitro Study

PubMed Central

Smith, Ida M.; Christensen, Jeffrey E.; Arneborg, Nils; Jespersen, Lene

2014-01-01

Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The concept of individual microorganisms influencing the makeup of T cell subsets via interactions with intestinal dendritic cells (DCs) appears to constitute the foundation for immunoregulatory effects of probiotics, and several studies have reported probiotic strains resulting in reduction of intestinal inflammation through modulation of DC function. Consequent to a focus on Saccharomyces boulardii as the fundamental probiotic yeast, very little is known about hundreds of non-Saccharomyces yeasts in terms of their interaction with the human gastrointestinal immune system. The aim of the present study was to evaluate 170 yeast strains representing 75 diverse species for modulation of inflammatory cytokine secretion by human DCs in vitro, as compared to cytokine responses induced by a S. boulardii reference strain with probiotic properties documented in clinical trials. Furthermore, we investigated whether cytokine inducing interactions between yeasts and human DCs are dependent upon yeast viability or rather a product of membrane interactions regardless of yeast metabolic function. We demonstrate high diversity in yeast induced cytokine profiles and employ multivariate data analysis to reveal distinct clustering of yeasts inducing similar cytokine profiles in DCs, highlighting clear species distinction within specific yeast genera. The observed differences in induced DC cytokine profiles add to the currently very limited knowledge of the cross-talk between yeasts and human immune cells and provide a foundation for selecting yeast strains for further characterization and development toward potentially novel yeast probiotics. Additionally, we present data to support a hypothesis that the interaction between yeasts and human DCs does not solely depend on yeast viability, a concept which may suggest a need for further classifications beyond the current definition of a probiotic. PMID:24816850

Assessment of serum biomarkers in rats after exposure to pesticides of different chemical classes

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

Moser, Virginia C., E-mail: Moser.ginger@epa.gov; Stewart, Nicholas; Freeborn, Danielle L.

There is increasing emphasis on the use of biomarkers of adverse outcomes in safety assessment and translational research. We evaluated serum biomarkers and targeted metabolite profiles after exposure to pesticides (permethrin, deltamethrin, imidacloprid, carbaryl, triadimefon, fipronil) with different neurotoxic actions. Adult male Long–Evans rats were evaluated after single exposure to vehicle or one of two doses of each pesticide at the time of peak effect. The doses were selected to produce similar magnitude of behavioral effects across chemicals. Serum or plasma was analyzed using commercial cytokine/protein panels and targeted metabolomics. Additional studies of fipronil used lower doses (lacking behavioral effects),more » singly or for 14 days, and included additional markers of exposure and biological activity. Biomarker profiles varied in the number of altered analytes and patterns of change across pesticide classes, and discriminant analysis could separate treatment groups from control. Low doses of fipronil produced greater effects when given for 14 days compared to a single dose. Changes in thyroid hormones and relative amounts of fipronil and its sulfone metabolite also differed between the dosing regimens. Most cytokine changes reflected alterations in inflammatory responses, hormone levels, and products of phospholipid, fatty acid, and amino acid metabolism. These findings demonstrate distinct blood-based analyte profiles across pesticide classes, dose levels, and exposure duration. These results show promise for detailed analyses of these biomarkers and their linkages to biological pathways. - Highlights: • Pesticides typical of different classes produced distinct patterns of change in biomarker panels. • Based on the panels used, alterations suggest impacts on immune, metabolism, and homeostasis functions. • Some changes may reflect actions on neurotransmitter systems involved in immune modulation. • Fipronil effects on thyroid and kinetics differed with acute and repeated administration.« less

Effects of berberine on a rat model of chronic stress and depression via gastrointestinal tract pathology and gastrointestinal flora profile assays.

PubMed

Zhu, Xiaohui; Sun, Yangdong; Zhang, Chenggang; Liu, Haifeng

2017-05-01

Chronic stress and depression are challenging conditions to treat, owing to their complexity and lack of clinically available and effective therapeutic agents. The aim of the present study was to investigate the mechanism by which berberine acts, by examining alterations to gastrointestinal tract histopathology and flora profile in a rat model, following the induction of stress. Research associating gastrointestinal flora and depression has increased, thus, the present study hypothesized that stress induces depression and changes in the gastrointestinal system. The chronic mild stress rat model was previously established based on a set of 10 chronic unpredictable stress methods. In the present study, the measurements of body weight, behavior, gastrointestinal tract histopathology and gastrointestinal flora profile were collected in order to elucidate understanding of chronic stress and depression in this region. In the present study, induced stress and the resulting depression was demonstrated to significantly decrease the body weight and sucrose preference of rats, as well as significantly increasing traverse time, vertical movement time, grooming time and motionless time in an open‑field test. Following modeling and subsequent treatment with low or high doses of berberine, the measurements were significantly different when compared with unstressed rats. Berberine appears to reverse the physical damage brought about by stress within the gastric mucosa and intestinal microvilli of the stomach, ileum, cecum and colon. Using enterobacterial repetitive intergenic consensus sequence‑based polymerase chain reaction analysis, several distinctive bands disappeared following modeling; however, novel distinctive bands appeared in response to the graded berberine treatment. In conclusion, the present study identified that high concentrations of berberine markedly protects rats from various symptoms of chronic stress and depression, with the potential of facilitating treatment within clinical practice.

Applicability of radar subsurface profiling in estimating sidewalk undermining.

DOT National Transportation Integrated Search

1979-01-01

An evaluation was made of the applicability of the geophysical technique of radar subsurface profiling to estimating the extent of sidewalk undermining. It was found that there is a distinct difference between the observed radar echo patterns of a no...

Subtropical Low Cloud Responses to Central and Eastern Pacific El Nino Events

NASA Astrophysics Data System (ADS)

Rapp, A. D.; Bennartz, R.; Jiang, J. H.; Kato, S.; Olson, W. S.; Pinker, R. T.; Su, H.; Taylor, P. C.

2014-12-01

The eastern Pacific El Niño event in 2006-2007 and the central Pacific El Niño event during 2009-2010 exhibit opposite responses in the top of atmosphere (TOA) cloud radiative effects. These responses are driven by differences in large-scale circulation that result in significant low cloud anomalies in the subtropical southeastern Pacific. Both the vertical profile of cloud fraction and cloud water content are reduced during the eastern Pacific El Niño; however, the shift in the distribution of cloud characteristics and the physical processes underlying these changes need further analysis. The NASA Energy and Water Cycle Study (NEWS) Clouds and Radiation Working Group will use a synthesis of NEWS data products, A-Train satellite measurements, reanalysis, and modeling approaches to further explore the differences in the low cloud response to changes in the large-scale forcing, as well as try to understand the physical mechanism driving the observed changes in the low clouds for the 2006/07 and 2009/10 distinct El Niño events. The distributions of cloud macrophysical, microphysical, and radiative properties over the southeast Pacific will first be compared for these two events using a combination of MODIS, CloudSat/CALIPSO, and CERES data. Satellite and reanalysis estimates of changes in the vertical temperature and moisture profiles, lower tropospheric stability, winds, and surface heat fluxes are then used to identify the drivers for observed differences in the clouds and TOA radiative effects.

Mothers' Vagal Regulation During the Still-Face Paradigm: Normative Reactivity and Impact of Depression Symptoms

PubMed Central

Oppenheimer, Julia E.; Measelle, Jeffrey R.; Laurent, Heidemarie K.; Ablow, Jennifer C.

2013-01-01

This study examined mothers' physiological reactivity in response to infant distress during the Still-Face Paradigm. We aimed to explore normative regulatory profiles and associated physiological and behavioral processes in order to further our understanding of what constitutes regulation in this dyadic context. We examined physiological patterns—vagal tone, indexed by respiratory sinus arrhythmia (RSA)-- while mothers maintained a neutral expression over the course of the still face episode, as well as differential reactivity patterns in mothers with depression symptoms compared to non-depressed mothers. Behavioral and physiological data were collected from mothers of 5-month-old infants during the emotion suppression phase of the Still-Face Paradigm. We used Hierarchical Linear Modeling to examine changes in mothers' RSA during infant distress and explored maternal depression as a predictor of physiological profiles. Mothers were generally able to maintain a neutral expression and simultaneously demonstrated a mean-level increase in RSA during the still face episode compared to baseline, indicating an active regulatory response overall. A more detailed time-course examination of RSA trajectories revealed that an initial RSA increase was typically followed by a decrease in response to peak infant distress, suggesting a physiological mobilization response. However, this was not true of mothers with elevated depressive symptoms, who showed no change in RSA during infant distress. These distinct patterns of infant distress-related physiological activation may help to explain differences in maternal sensitivity and adaptive parenting. PMID:23454427

Octreotide and pasireotide (dis)similarly inhibit pituitary tumor cells in vitro.

PubMed

Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C; Gahete, Manuel D; Jiménez-Reina, Luis; Venegas-Moreno, Eva; de la Riva, Andrés; Arráez, Miguel Ángel; González-Molero, Inmaculada; Schmid, Herbert A; Maraver-Selfa, Silvia; Gavilán-Villarejo, Inmaculada; García-Arnés, Juan Antonio; Japón, Miguel A; Soto-Moreno, Alfonso; Gálvez, María A; Luque, Raúl M; Castaño, Justo P

2016-11-01

Somatostatin analogs (SSA) are the mainstay of pharmacological treatment for pituitary adenomas. However, some patients escape from therapy with octreotide, a somatostatin receptor 2 (sst2)-preferring SSA, and pasireotide, a novel multi-sst-preferring SSA, may help to overcome this problem. It has been proposed that correspondence between sst1-sst5 expression pattern and SSA-binding profile could predict patient's response. To explore the cellular/molecular features associated with octreotide/pasireotide response, we performed a parallel comparison of their in vitro effects, evaluating sst1-sst5 expression, intracellular Ca 2+ signaling ([Ca 2+ ] i ), hormone secretion and cell viability, in a series of 85 pituitary samples. Somatotropinomas expressed sst5>sst2, yet octreotide reduced [Ca 2+ ] i more efficiently than pasireotide, while both SSA similarly decreased growth hormone release/expression and viability. Corticotropinomas predominantly expressed sst5, but displayed limited response to pasireotide, while octreotide reduced functional endpoints. Non-functioning adenomas preferentially expressed sst3 but, surprisingly, both SSA increased cell viability. Prolactinomas mainly expressed sst1 but were virtually unresponsive to SSA. Finally, both SSA decreased [Ca 2+ ] i in normal pituitaries. In conclusion, both SSA act in vitro on pituitary adenomas exerting both similar and distinct effects; however, no evident correspondence was found with the sst1-sst5 profile. Thus, it seems plausible that additional factors, besides the simple abundance of a given sst, critically influence the SSA response. © 2016 Society for Endocrinology.

Patterns of gene expression reveal a temporally orchestrated wound healing response in the injured spinal cord.

PubMed

Velardo, Margaret J; Burger, Corinna; Williams, Philip R; Baker, Henry V; López, M Cecilia; Mareci, Thomas H; White, Todd E; Muzyczka, Nicholas; Reier, Paul J

2004-09-29

Spinal cord injury (SCI) induces a progressive pathophysiology affecting cell survival and neurological integrity via complex and evolving molecular cascades whose interrelationships are not fully understood. The present experiments were designed to: (1) determine potential functional interactions within transcriptional expression profiles obtained after a clinically relevant SCI and (2) test the consistency of transcript expression after SCI in two genetically and immunologically diverse rat strains characterized by differences in T cell competence and associated inflammatory responses. By interrogating Affymetrix U34A rat genome GeneChip microarrays, we defined the transcriptional expression patterns in midcervical contusion lesion sites between 1 and 90 d postinjury of athymic nude (AN) and Sprague Dawley (SD) strains. Stringent statistical analyses detected significant changes in 3638 probe sets, with 80 genes differing between the AN and SD groups. Subsequent detailed functional categorization of these transcripts unveiled an overall tissue remodeling response that was common to both strains. The functionally organized gene profiles were temporally distinct and correlated with repair indices observed microscopically and by magnetic resonance microimaging. Our molecular and anatomical observations have identified a novel, longitudinal perspective of the post-SCI response, namely, that of a highly orchestrated tissue repair and remodeling repertoire with a prominent cutaneous wound healing signature that is conserved between two widely differing rat strains. These results have significant bearing on the continuing development of cellular and pharmacological therapeutics directed at tissue rescue and neuronal regeneration in the injured spinal cord.

TP53, STK11 and EGFR Mutations Predict Tumor Immune Profile and the Response to anti-PD-1 in Lung Adenocarcinoma.

PubMed

Biton, Jerome; Mansuet-Lupo, Audrey; Pécuchet, Nicolas; Alifano, Marco; Ouakrim, Hanane; Arrondeau, Jennifer; Boudou-Rouquette, Pascaline; Goldwasser, Francois; Leroy, Karen; Goc, Jeremy; Wislez, Marie; Germain, Claire; Laurent-Puig, Pierre; Dieu-Nosjean, Marie-Caroline; Cremer, Isabelle; Herbst, Ronald; Blons, Hélène F; Damotte, Diane

2018-05-15

By unlocking anti-tumor immunity, antibodies targeting programmed cell death 1 (PD-1) exhibit impressive clinical results in non-small cell lung cancer, underlining the strong interactions between tumor and immune cells. However, factors that can robustly predict long-lasting responses are still needed. We performed in depth immune profiling of lung adenocarcinoma using an integrative analysis based on immunohistochemistry, flow-cytometry and transcriptomic data. Tumor mutational status was investigated using next-generation sequencing. The response to PD-1 blockers was analyzed from a prospective cohort according to tumor mutational profiles and to PD-L1 expression, and a public clinical database was used to validate the results obtained. We showed that distinct combinations of STK11 , EGFR and TP53 mutations, were major determinants of the tumor immune profile (TIP) and of the expression of PD-L1 by malignant cells. Indeed, the presence of TP53 mutations without co-occurring STK11 or EGFR alterations ( TP53 -mut/ STK11 - EGFR -WT), independently of KRAS mutations, identified the group of tumors with the highest CD8 T cell density and PD-L1 expression. In this tumor subtype, pathways related to T cell chemotaxis, immune cell cytotoxicity, and antigen processing were up-regulated. Finally, a prolonged progression-free survival (PFS: HR=0.32; 95% CI, 0.16-0.63, p <0.001) was observed in anti-PD-1 treated patients harboring TP53 -mut/ STK11 - EGFR -WT tumors. This clinical benefit was even more remarkable in patients with associated strong PD-L1 expression. Our study reveals that different combinations of TP53 , EGFR and STK11 mutations , together with PD-L1 expression by tumor cells, represent robust parameters to identify best responders to PD-1 blockade. Copyright ©2018, American Association for Cancer Research.

DNA methylation profile distinguishes clear cell sarcoma of the kidney from other pediatric renal tumors.

PubMed

Ueno, Hitomi; Okita, Hajime; Akimoto, Shingo; Kobayashi, Kenichiro; Nakabayashi, Kazuhiko; Hata, Kenichiro; Fujimoto, Junichiro; Hata, Jun-Ichi; Fukuzawa, Masahiro; Kiyokawa, Nobutaka

2013-01-01

A number of specific, distinct neoplastic entities occur in the pediatric kidney, including Wilms' tumor, clear cell sarcoma of the kidney (CCSK), congenital mesoblastic nephroma (CMN), rhabdoid tumor of the kidney (RTK), and the Ewing's sarcoma family of tumors (ESFT). By employing DNA methylation profiling using Illumina Infinium HumanMethylation27, we analyzed the epigenetic characteristics of the sarcomas including CCSK, RTK, and ESFT in comparison with those of the non-neoplastic kidney (NK), and these tumors exhibited distinct DNA methylation profiles in a tumor-type-specific manner. CCSK is the most frequently hypermethylated, but least frequently hypomethylated, at CpG sites among these sarcomas, and exhibited 490 hypermethylated and 46 hypomethylated CpG sites in compared with NK. We further validated the results by MassARRAY, and revealed that a combination of four genes was sufficient for the DNA methylation profile-based differentiation of these tumors by clustering analysis. Furthermore, THBS1 CpG sites were found to be specifically hypermethylated in CCSK and, thus, the DNA methylation status of these THBS1 sites alone was sufficient for the distinction of CCSK from other pediatric renal tumors, including Wilms' tumor and CMN. Moreover, combined bisulfite restriction analysis could be applied for the detection of hypermethylation of a THBS1 CpG site. Besides the biological significance in the pathogenesis, the DNA methylation profile should be useful for the differential diagnosis of pediatric renal tumors.

Racial discrimination experiences and African American youth adjustment: The role of parenting profiles based on racial socialization and involved-vigilant parenting.

PubMed

Varner, Fatima A; Hou, Yang; Hodzic, Tajma; Hurd, Noelle M; Butler-Barnes, Sheretta T; Rowley, Stephanie J

2018-04-01

The purpose of this study was to test whether parenting profiles based on racial socialization and involved-vigilant parenting would compensate for or moderate associations between racial discrimination experiences and academic outcomes and psychological well-being among African American adolescents. Participants were 1,363 African American adolescents (M age = 14.19; 52.3% female) from 3 Midwestern suburban school districts. Latent profile analysis was used to examine whether there were distinct combinations of parenting. The relationships among racial discrimination experiences, parenting profiles, and adjustment were examined using structural equation modeling (SEM). Three distinct parenting profiles were found: moderate positive (n = 767; moderately high involved-vigilant parenting and racial barrier, racial pride, behavioral, and egalitarian messages, and low negative messages), unengaged (n = 351; low racial socialization messages and moderately low involved-vigilant parenting), and high negative parenting (n = 242; high negative messages, moderate other racial socialization messages, and moderately low involved-vigilant parenting). Racial discrimination experiences were negatively associated with youth adjustment. Moderate positive parenting was related to the best academic outcomes and unengaged parenting was associated with more positive academic outcomes than high negative parenting. Moderate positive parenting was associated with better psychological well-being than unengaged or high negative parenting although the benefits were greater for adolescents with fewer racial discrimination experiences. Distinct patterns of racial socialization messages and involved-vigilant parenting contribute to differences in African American youth adjustment. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Unique and shared inflammatory profiles of human brain endothelia and pericytes.

PubMed

Smyth, Leon C D; Rustenhoven, Justin; Park, Thomas I-H; Schweder, Patrick; Jansson, Deidre; Heppner, Peter A; O'Carroll, Simon J; Mee, Edward W; Faull, Richard L M; Curtis, Maurice; Dragunow, Mike

2018-05-11

Pericytes and endothelial cells are critical cellular components of the blood-brain barrier (BBB) and play an important role in neuroinflammation. To date, the majority of inflammation-related studies in endothelia and pericytes have been carried out using immortalised cell lines or non-human-derived cells. Whether these are representative of primary human cells is unclear and systematic comparisons of the inflammatory responses of primary human brain-derived pericytes and endothelia has yet to be performed. To study the effects of neuroinflammation at the BBB, primary brain endothelial cells and pericytes were isolated from human biopsy tissue. Culture purity was examined using qPCR and immunocytochemistry. Electrical cell-substrate impedance sensing (ECIS) was used to determine the barrier properties of endothelial and pericyte cultures. Using immunocytochemistry, cytometric bead array, and ECIS, we compared the responses of endothelia and pericytes to a panel of inflammatory stimuli (IL-1β, TNFα, LPS, IFN-γ, TGF-β 1 , IL-6, and IL-4). Secretome analysis was performed to identify unique secretions of endothelia and pericytes in response to IL-1β. Endothelial cells were pure, moderately proliferative, retained the expression of BBB-related junctional proteins and transporters, and generated robust TEER. Both endothelia and pericytes have the same pattern of transcription factor activation in response to inflammatory stimuli but respond differently at the secretion level. Secretome analysis confirmed that endothelia and pericytes have overlapping but distinct secretome profiles in response to IL-1β. We identified several cell-type specific responses, including G-CSF and GM-CSF (endothelial-specific), and IGFBP2 and IGFBP3 (pericyte-specific). Finally, we demonstrated that direct addition of IL-1β, TNFα, LPS, and IL-4 contributed to the loss of endothelial barrier integrity in vitro. Here, we identify important cell-type differences in the inflammatory response of brain pericytes and endothelia and provide, for the first time, a comprehensive profile of the secretions of primary human brain endothelia and pericytes which has implications for understanding how inflammation affects the cerebrovasculature.

Chemical combination effects predict connectivity in biological systems

PubMed Central

Lehár, Joseph; Zimmermann, Grant R; Krueger, Andrew S; Molnar, Raymond A; Ledell, Jebediah T; Heilbut, Adrian M; Short, Glenn F; Giusti, Leanne C; Nolan, Garry P; Magid, Omar A; Lee, Margaret S; Borisy, Alexis A; Stockwell, Brent R; Keith, Curtis T

2007-01-01

Efforts to construct therapeutically useful models of biological systems require large and diverse sets of data on functional connections between their components. Here we show that cellular responses to combinations of chemicals reveal how their biological targets are connected. Simulations of pathways with pairs of inhibitors at varying doses predict distinct response surface shapes that are reproduced in a yeast experiment, with further support from a larger screen using human tumour cells. The response morphology yields detailed connectivity constraints between nearby targets, and synergy profiles across many combinations show relatedness between targets in the whole network. Constraints from chemical combinations complement genetic studies, because they probe different cellular components and can be applied to disease models that are not amenable to mutagenesis. Chemical probes also offer increased flexibility, as they can be continuously dosed, temporally controlled, and readily combined. After extending this initial study to cover a wider range of combination effects and pathway topologies, chemical combinations may be used to refine network models or to identify novel targets. This response surface methodology may even apply to non-biological systems where responses to targeted perturbations can be measured. PMID:17332758

Phenotypic characteristics of adolescents with concave and convex facial profiles - The National Health Examination Survey.

PubMed

Hujoel, P P; Bollen, A-M; Yuen, K C J; Hujoel, I A

2016-10-01

It has been suggested that facial traits are informative on the inherited susceptibility to tuberculosis and obesity, two current global health issues. Our aim was to compare the phenotypic characteristics of adolescents with dental markers for a concave (n=420), a convex (n=978), and a straight (n=3542) facial profile in a nationally representative sample of United States adolescents. The results show that adolescents with a concave facial profile, when compared to a straight facial profile, had an increased waist-to-height ratio (Δ, 1.1 [95% CI 0.5-1.7], p<0.003) and an increased acne prevalence (OR, 1.5 [95% CI 1.2-1.9], p<0.001). Adolescents with a convex facial profile, when compared to a straight facial profile, had an increased prevalence of tuberculosis (OR, 4.3 [95% CI 1.4-13.1], p<0.02), increased ectomorphy (Δ, 0.3 [95% CI 0.2-0.4], p<0.0001), increased left-handedness (OR, 1.4 [95% CI 1.1-1.7], p<0.007), increased color-blindness (OR, 1.7 [95% CI 1.3-2.3], p<0.004), and rhesus ee phenotype (OR, 1.3 [95% CI 1.1-1.5], p<0.008). Adolescents with a concave facial profile, when compared to a convex profile, had increased mesomorphy (Δ, 1.3 [95% CI 1.1-1.5], p<0.0001), increased endomorphy (Δ, 0.5 [95% CI 0.4-0.6], p<0.0001), lower ectomorphy (Δ, 0.5 [95% CI 0.4-0.6], p<0.0001), and lower vocabulary test scores (Δ, 2.3 [95% CI 0.8-3.8], p<0.008). It is concluded that population-based survey data confirm that distinct facial features are associated with distinct somatotypes and distinct disease susceptibilities. Copyright © 2016 Elsevier GmbH. All rights reserved.

Novel Therapeutics for Multiple Sclerosis Designed by Parasitic Worms

PubMed Central

Dixit, Aakanksha; Tanaka, Akane; Greer, Judith M.

2017-01-01

The evolutionary response to endemic infections with parasitic worms (helminth) was the development of a distinct regulatory immune profile arising from the need to encapsulate the helminths while simultaneously repairing tissue damage. According to the old friend’s hypothesis, the diminished exposure to these parasites in the developed world has resulted in a dysregulated immune response that contributes to the increased incidence of immune mediated diseases such as Multiple Sclerosis (MS). Indeed, the global distribution of MS shows an inverse correlation to the prevalence of helminth infection. On this basis, the possibility of treating MS with helminth infection has been explored in animal models and phase 1 and 2 human clinical trials. However, the possibility also exists that the individual immune modulatory molecules secreted by helminth parasites may offer a more defined therapeutic strategy. PMID:29027962

Fingerprints of Modified RNA Bases from Deep Sequencing Profiles.

PubMed

Kietrys, Anna M; Velema, Willem A; Kool, Eric T

2017-11-29

Posttranscriptional modifications of RNA bases are not only found in many noncoding RNAs but have also recently been identified in coding (messenger) RNAs as well. They require complex and laborious methods to locate, and many still lack methods for localized detection. Here we test the ability of next-generation sequencing (NGS) to detect and distinguish between ten modified bases in synthetic RNAs. We compare ultradeep sequencing patterns of modified bases, including miscoding, insertions and deletions (indels), and truncations, to unmodified bases in the same contexts. The data show widely varied responses to modification, ranging from no response, to high levels of mutations, insertions, deletions, and truncations. The patterns are distinct for several of the modifications, and suggest the future use of ultradeep sequencing as a fingerprinting strategy for locating and identifying modifications in cellular RNAs.

Adolescent transformations of behavioral and neural processes as potential targets for prevention.

PubMed

Eldreth, Dana; Hardin, Michael G; Pavletic, Nevia; Ernst, Monique

2013-06-01

Adolescence is a transitional period in development that is marked by a distinct, typical behavioral profile of high rates of exploration, novelty-seeking, and emotional lability. While these behaviors generally assist the adolescent transition to independence, they can also confer vulnerability for excessive risk-taking and psychopathology, particularly in the context of specific environmental or genetic influences. As prevention research depends on the identification of targets of vulnerability, the following review will discuss the interplay among motivational systems including reward-related, avoidance-related, and regulatory processes in typical and atypical adolescent development. Each set of processes will be discussed in relation to their underlying neural correlates and distinct developmental trajectories. Evidence suggests that typical adolescent behavior and the risk for atypical development are mediated by heightened adolescent responsiveness of reward-related and avoidance-related systems under specific conditions, concurrent with poor modulation by immature regulatory processes. Finally, we will propose strategies to exploit heightened reward processing to reinforce inhibitory control, which is an essential component of regulatory processes in prevention interventions.

Posttranslational Modifications of p53 in Replicative Senescence Overlapping but Distinct from Those Induced by DNA Damage

PubMed Central

Webley, Katherine; Bond, Jane A.; Jones, Christopher J.; Blaydes, Jeremy P.; Craig, Ashley; Hupp, Ted; Wynford-Thomas, David

2000-01-01

Replicative senescence in human fibroblasts is absolutely dependent on the function of the phosphoprotein p53 and correlates with activation of p53-dependent transcription. However, no evidence for posttranslational modification of p53 in senescence has been presented, raising the possibility that changes in transcriptional activity result from upregulation of a coactivator. Using a series of antibodies with phosphorylation-sensitive epitopes, we now show that senescence is associated with major changes at putative regulatory sites in the N and C termini of p53 consistent with increased phosphorylation at serine-15, threonine-18, and serine-376 and decreased phosphorylation at serine-392. Ionizing and UV radiation generated overlapping but distinct profiles of response, with increased serine-15 phosphorylation being the only common change. These results support a direct role for p53 in signaling replicative senescence and are consistent with the generation by telomere erosion of a signal which shares some but not all of the features of DNA double-strand breaks. PMID:10733583

Rabies in southeast Brazil: a change in the epidemiological pattern.

PubMed

Queiroz, Luzia Helena; Favoretto, Silvana Regina; Cunha, Elenice Maria S; Campos, Angélica Cristine A; Lopes, Marissol Cardoso; de Carvalho, Cristiano; Iamamoto, Keila; Araújo, Danielle Bastos; Venditti, Leandro Lima R; Ribeiro, Erica S; Pedro, Wagner André; Durigon, Edison Luiz

2012-01-01

This epidemiological study was conducted using antigenic and genetic characterisation of rabies virus isolates obtained from different animal species in the southeast of Brazil from 1993 to 2007. An alteration in the epidemiological profile was observed. One hundred two samples were tested using a panel of eight monoclonal antibodies, and 94 were genetically characterised by sequencing the nucleoprotein gene. From 1993 to 1997, antigenic variant 2 (AgV-2), related to a rabies virus maintained in dog populations, was responsible for rabies cases in dogs, cats, cattle and horses. Antigenic variant 3 (AgV-3), associated with Desmodus rotundus, was detected in a few cattle samples from rural areas. From 1998 to 2007, rabies virus was detected in bats and urban pets, and four distinct variants were identified. A nucleotide similarity analysis resulted in two primary groups comprising the dog and bat antigenic variants and showing the distinct endemic cycles maintained in the different animal species in this region.

[The role of microRNAs in head and neck squamous cell carcinoma : Biomarkers for prognosis, therapy selection, and novel therapeutics].

PubMed

Heß, A K; Weichert, W; Budach, V; Tinhofer, I

2016-05-01

Despite recent advances in radiochemotherapy, treatment of locally advanced head and neck squamous cell carcinoma is still challenging, and survival rates have improved only slightly. This is due to the high frequency of metastases and local and/or regional tumor recurrences that have acquired radio- or chemoresistance. MiRNAs regulate diverse processes in tumorigenesis, metastasis, and therapy resistance in head and neck squamous cell carcinoma. Hence, miRNAs are highly valued in biomarker studies. Establishment of the miRNA profiles of oropharyngeal tumors enables personalized treatment selection, since expression of distinct miRNAs can predict the response to two different radiochemotherapy regimens. Development of novel miRNA therapeutics has a high clinical potential for further improving treatment of cancerous disease. The use of nanoparticles with distinct surface modifications as miRNA vectors permits prolonged bioavailability, high efficacy in tumor targeting, and low toxicity. Nevertheless, the efficacy of miRNA therapy has only been shown in animal models to date.

Profiling and Quantification of Phenolics in Stevia rebaudiana Leaves.

PubMed

Karaköse, Hande; Müller, Anja; Kuhnert, Nikolai

2015-10-21

Stevia rebaudiana (Bertoni) is a plant from the Asteraceae family with significant economic value because of the steviol glycoside sweeteners in its leaves. Chlorogenic acids and flavonoid glycosides of S. rebaudiana from seven different botanical varieties cultivated over two years and harvested three times a year in eight European locations were profiled and quantified in a total of 166 samples. Compounds quantified include chlorogenic acids as well as flavonoid glycosides and aglycons. All phenolic concentration profiles show a perfect Gaussian distribution. Principal component analyses allow distinction between varieties of different geographical origin and distinction between different plant varieties. Although concentrations of all chlorogenic acids showed a positive correlation, no correlation was observed for flavonoid glycosides. Conclusions from these findings with respect to the biosynthesis and functional role of phenolics in S. rebaudiana are discussed.

Phosphoprotein profiles of candidate markers for early cellular responses to low-dose γ-radiation in normal human fibroblast cells

PubMed Central

Yim, Ji-Hye; Yun, Jung Mi; Kim, Ji Young; Lee, In Kyung; Nam, Seon Young

2017-01-01

Abstract Ionizing radiation causes biological damage that leads to severe health effects. However, the effects and subsequent health implications caused by exposure to low-dose radiation are unclear. The objective of this study was to determine phosphoprotein profiles in normal human fibroblast cell lines in response to low-dose and high-dose γ-radiation. We examined the cellular response in MRC-5 cells 0.5 h after exposure to 0.05 or 2 Gy. Using 1318 antibodies by antibody array, we observed ≥1.3-fold increases in a number of identified phosphoproteins in cells subjected to low-dose (0.05 Gy) and high-dose (2 Gy) radiation, suggesting that both radiation levels stimulate distinct signaling pathways. Low-dose radiation induced nucleic acid–binding transcription factor activity, developmental processes, and multicellular organismal processes. By contrast, high-dose radiation stimulated apoptotic processes, cell adhesion and regulation, and cellular organization and biogenesis. We found that phospho-BTK (Tyr550) and phospho-Gab2 (Tyr643) protein levels at 0.5 h after treatment were higher in cells subjected to low-dose radiation than in cells treated with high-dose radiation. We also determined that the phosphorylation of BTK and Gab2 in response to ionizing radiation was regulated in a dose-dependent manner in MRC-5 and NHDF cells. Our study provides new insights into the biological responses to low-dose γ-radiation and identifies potential candidate markers for monitoring exposure to low-dose ionizing radiation. PMID:28122968

Passion and intrinsic motivation in digital gaming.

PubMed

Wang, Chee Keng John; Khoo, Angeline; Liu, Woon Chia; Divaharan, Shanti

2008-02-01

Digital gaming is fast becoming a favorite activity all over the world. Yet very few studies have examined the underlying motivational processes involved in digital gaming. One motivational force that receives little attention in psychology is passion, which could help us understand the motivation of gamers. The purpose of the present study was to identify subgroups of young people with distinctive passion profiles on self-determined regulations, flow dispositions, affect, and engagement time in gaming. One hundred fifty-five students from two secondary schools in Singapore participated in the survey. There were 134 males and 8 females (13 unspecified). The participants completed a questionnaire to measure harmonious passion (HP), obsessive passion (OP), perceived locus of causality, disposition flow, positive and negative affects, and engagement time in gaming. Cluster analysis found three clusters with distinct passion profiles. The first cluster had an average HP/OP profile, the second cluster had a low HP/OP profile, and the third cluster had a high HP/OP profile. The three clusters displayed different levels of cognitive, affective, and behavioral outcomes. Cluster analysis, as this study shows, is useful in identifying groups of gamers with different passion profiles. It has helped us gain a deeper understanding of motivation in digital gaming.

Face-selective neurons maintain consistent visual responses across months

PubMed Central

McMahon, David B. T.; Jones, Adam P.; Bondar, Igor V.; Leopold, David A.

2014-01-01

Face perception in both humans and monkeys is thought to depend on neurons clustered in discrete, specialized brain regions. Because primates are frequently called upon to recognize and remember new individuals, the neuronal representation of faces in the brain might be expected to change over time. The functional properties of neurons in behaving animals are typically assessed over time periods ranging from minutes to hours, which amounts to a snapshot compared to a lifespan of a neuron. It therefore remains unclear how neuronal properties observed on a given day predict that same neuron's activity months or years later. Here we show that the macaque inferotemporal cortex contains face-selective cells that show virtually no change in their patterns of visual responses over time periods as long as one year. Using chronically implanted microwire electrodes guided by functional MRI targeting, we obtained distinct profiles of selectivity for face and nonface stimuli that served as fingerprints for individual neurons in the anterior fundus (AF) face patch within the superior temporal sulcus. Longitudinal tracking over a series of daily recording sessions revealed that face-selective neurons maintain consistent visual response profiles across months-long time spans despite the influence of ongoing daily experience. We propose that neurons in the AF face patch are specialized for aspects of face perception that demand stability as opposed to plasticity. PMID:24799679

Face-selective neurons maintain consistent visual responses across months.

PubMed

McMahon, David B T; Jones, Adam P; Bondar, Igor V; Leopold, David A

2014-06-03

Face perception in both humans and monkeys is thought to depend on neurons clustered in discrete, specialized brain regions. Because primates are frequently called upon to recognize and remember new individuals, the neuronal representation of faces in the brain might be expected to change over time. The functional properties of neurons in behaving animals are typically assessed over time periods ranging from minutes to hours, which amounts to a snapshot compared to a lifespan of a neuron. It therefore remains unclear how neuronal properties observed on a given day predict that same neuron's activity months or years later. Here we show that the macaque inferotemporal cortex contains face-selective cells that show virtually no change in their patterns of visual responses over time periods as long as one year. Using chronically implanted microwire electrodes guided by functional MRI targeting, we obtained distinct profiles of selectivity for face and nonface stimuli that served as fingerprints for individual neurons in the anterior fundus (AF) face patch within the superior temporal sulcus. Longitudinal tracking over a series of daily recording sessions revealed that face-selective neurons maintain consistent visual response profiles across months-long time spans despite the influence of ongoing daily experience. We propose that neurons in the AF face patch are specialized for aspects of face perception that demand stability as opposed to plasticity.

Response of human renal tubular cells to cyclosporine and sirolimus: A toxicogenomic study

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

Pallet, Nicolas; Rabant, Marion; Xu-Dubois, Yi-Chun

The molecular mechanisms involved in the potentially nephrotoxic response of tubular cells to immunosuppressive drugs remain poorly understood. Transcriptional profiles of human proximal tubular cells exposed to cyclosporine A (CsA), sirolimus (SRL) or their combination, were established using oligonucleotide microarrays. Hierarchical clustering of genes implicated in fibrotic processes showed a clear distinction between expression profiles with CsA and CsA + SRL treatments on the one hand and SRL treatment on the other. Functional analysis found that CsA and CsA + SRL treatments preferentially alter biological processes located at the cell membrane, such as ion transport or signal transduction, whereas SRLmore » modifies biological processes within the nucleus and related to transcriptional activity. Genome wide expression analysis suggested that CsA may induce an endoplasmic reticulum (ER) stress in tubular cells in vitro. Moreover we found that CsA exposure in vivo is associated with the upregulation of the ER stress marker BIP in kidney transplant biopsies. In conclusion, this toxicogenomic study highlights the molecular interaction networks that may contribute to the tubular response to CsA and SRL. These results may also offer a new working hypothesis for future research in the field of CsA nephrotoxicity. Further studies are needed to evaluate if ER stress detection in tubular cells in human biopsies can predict CsA nephrotoxicity.« less

Molecular profiling of ALDH1+ colorectal cancer stem cells reveals preferential activation of MAPK, FAK, and oxidative stress pro-survival signalling pathways.

PubMed

Vishnubalaji, Radhakrishnan; Manikandan, Muthurangan; Fahad, Mohamed; Hamam, Rimi; Alfayez, Musaad; Kassem, Moustapha; Aldahmash, Abdullah; Alajez, Nehad M

2018-03-02

Tumour heterogeneity leads to variable clinical response and inaccurate diagnostic and prognostic assessment. Cancer stem cells (CSCs) represent a subpopulation responsible for invasion, metastasis, therapeutic resistance, and recurrence in many human cancer types. However, the true identity of colorectal cancer (CRC) SCs remains elusive. Here, we aimed to characterize and define the gene expression portrait of CSCs in CRC-model SW403 cells. We found that ALDH + positive cells are clonogenic and highly proliferative; their global gene expression profiling-based molecular signature revealed gene enrichment related to DNA damage, MAPK, FAK, oxidative stress response, and Wnt signalling. ALDH + cells showed enhanced ROS stress resistance, whereas MAPK/FAK pathway pharmacologic inhibition limited their survival. Conversely, 5-fluorouracil increased the ALDH + cell fraction among the SW403, HCT116 and SW620 CRC models. Notably, analysis of ALDH1A1 and POU5F1 expression levels in cohorts of 462 or 420 patients for overall (OS) or disease-free (DFS) survival, respectively, obtained from the Cancer Genome Atlas CRC dataset, revealed strong association between elevated expression and poor OS ( p = 0.006) and poor DFS ( p = 0.05), thus implicating ALDH1A1 and POU5F1 in CRC prognosis. Our data reveal distinct molecular signature of ALDH + CSCs in CRC and suggest pathways relevant for successful targeted therapies and management of CRC.

HIV skews the lineage-defining transcriptional profile of Mycobacterium tuberculosis-specific CD4+ T cells

PubMed Central

Riou, Catherine; Strickland, Natalie; Soares, Andreia P.; Corleis, Bjorn; Kwon, Douglas; Wherry, E. John; Wilkinson, Robert J.; Burgers, Wendy A.

2016-01-01

HIV-infected persons are at greater risk of developing tuberculosis (TB) even before profound CD4 loss occurs, suggesting that HIV alters CD4+T cell functions capable of containing bacterial replication. An effective immune response to Mycobacterium tuberculosis likely relies on the development of a balanced CD4 response, where distinct CD4+T helper subsets act in synergy to control the infection. To define the diversity of Mtb-specific CD4+Th subsets and determine whether HIV infection impacts such responses, the expression of lineage-defining transcription factors T-bet, Gata3, RORγt and Foxp3 was measured in Mtb-specific CD4+T cells in HIV-uninfected (n=20) and HIV-infected individuals (n=20) with latent TB infection. Our results show that upon 5 day restimulation in vitro, Mtb-specific CD4+T cells from healthy individuals have the ability to exhibit a broad spectrum of T helper subsets, defined by specific patterns of transcription factor co-expression. These transcription factor profiles were skewed in HIV-infected individuals where the proportion of T-bethighFoxp3+ Mtb-specific CD4+T cells was significantly decreased (p=0.002) compared to HIV-uninfected individuals, a change that correlated inversely with HIV viral load (p=0.0007) and plasma TNF-α (p=0.027). Our data demonstrate an important balance in T helper subset diversity defined by lineage-defining transcription factor co-expression profiles that is disrupted by HIV infection and suggest a role for HIV in impairing TB immunity by altering the equilibrium of Mtb-specific CD4+T helper subsets. PMID:26927799

Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes.

PubMed

Daskalakis, Nikolaos P; Cohen, Hagit; Cai, Guiqing; Buxbaum, Joseph D; Yehuda, Rachel

2014-09-16

Delineating the molecular basis of individual differences in the stress response is critical to understanding the pathophysiology and treatment of posttraumatic stress disorder (PTSD). In this study, 7 d after predator-scent-stress (PSS) exposure, male and female rats were classified into vulnerable (i.e., "PTSD-like") and resilient (i.e., minimally affected) phenotypes on the basis of their performance on a variety of behavioral measures. Genome-wide expression profiling in blood and two limbic brain regions (amygdala and hippocampus), followed by quantitative PCR validation, was performed in these two groups of animals, as well as in an unexposed control group. Differentially expressed genes were identified in blood and brain associated with PSS-exposure and with distinct behavioral profiles postexposure. There was a small but significant between-tissue overlap (4-21%) for the genes associated with exposure-related individual differences, indicating convergent gene expression in both sexes. To uncover convergent signaling pathways across tissue and sex, upstream activated/deactivated transcription factors were first predicted for each tissue and then the respective pathways were identified. Glucocorticoid receptor (GR) signaling was the only convergent pathway associated with individual differences when using the most stringent statistical threshold. Corticosterone treatment 1 h after PSS-exposure prevented anxiety and hyperarousal 7 d later in both sexes, confirming the GR involvement in the PSS behavioral response. In conclusion, genes and pathways associated with extreme differences in the traumatic stress behavioral response can be distinguished from those associated with trauma exposure. Blood-based biomarkers can predict aspects of brain signaling. GR signaling is a convergent signaling pathway, associated with trauma-related individual differences in both sexes.

Effects of heavy metals on Cyanothece sp. CCY 0110 growth, extracellular polymeric substances (EPS) production, ultrastructure and protein profiles.

PubMed

Mota, Rita; Pereira, Sara B; Meazzini, Marianna; Fernandes, Rui; Santos, Arlete; Evans, Caroline A; De Philippis, Roberto; Wright, Phillip C; Tamagnini, Paula

2015-04-29

The effects of several heavy metals on the growth/survival, EPS production, ultrastructure and protein profiles of the highly efficient extracellular polymeric substances (EPS)-producer cyanobacterium Cyanothece sp. CCY 0110 were evaluated. Our results clearly show that each heavy metal affects the cells in a particular manner, triggering distinctive responses. Concerning chronic exposure, cells were more affected by Cu(2+) followed by Pb(2+), Cd(2+), and Li(+). The presence of metal leads to remarkable ultrastructural changes, mainly at the thylakoid level. The comparison of the proteomes (iTRAQ) allowed to follow the stress responses and to distinguish specific effects related to the time of exposure and/or the concentration of an essential (Cu(2+)) and a non-essential (Cd(2+)) metal. The majority of the proteins identified and with fold changes were associated with photosynthesis, CO2 fixation and carbohydrate metabolism, translation, and nitrogen and amino acid metabolism. Moreover, our results indicate that during chronic exposure to sub-lethal concentrations of Cu(2+), the cells tune down their metabolic rate to invest energy in the activation of detoxification mechanisms, which eventually result in a remarkable recovery. In contrast, the toxic effects of Cd(2+) are cumulative. Unexpectedly, the amount of released polysaccharides (RPS) was not enhanced by the presence of heavy metals. This work shows the holistic effects of different heavy metals on the cells of the highly efficient EPS-producer the cyanobacterium Cyanothece sp. CCY 0110. The growth/survival, EPS production, ultrastructure, protein profiles and stress response were evaluated. The knowledge generated by this study will contribute to the implementation of heavy-metal removal systems based on cyanobacteria EPS or their isolated polymers. Copyright © 2015. Published by Elsevier B.V.

Comprehensive Genome-Wide Survey, Genomic Constitution and Expression Profiling of the NAC Transcription Factor Family in Foxtail Millet (Setaria italica L.)

PubMed Central

Puranik, Swati; Sahu, Pranav Pankaj; Mandal, Sambhu Nath; B., Venkata Suresh; Parida, Swarup Kumar; Prasad, Manoj

2013-01-01

The NAC proteins represent a major plant-specific transcription factor family that has established enormously diverse roles in various plant processes. Aided by the availability of complete genomes, several members of this family have been identified in Arabidopsis, rice, soybean and poplar. However, no comprehensive investigation has been presented for the recently sequenced, naturally stress tolerant crop, Setaria italica (foxtail millet) that is famed as a model crop for bioenergy research. In this study, we identified 147 putative NAC domain-encoding genes from foxtail millet by systematic sequence analysis and physically mapped them onto nine chromosomes. Genomic organization suggested that inter-chromosomal duplications may have been responsible for expansion of this gene family in foxtail millet. Phylogenetically, they were arranged into 11 distinct sub-families (I-XI), with duplicated genes fitting into one cluster and possessing conserved motif compositions. Comparative mapping with other grass species revealed some orthologous relationships and chromosomal rearrangements including duplication, inversion and deletion of genes. The evolutionary significance as duplication and divergence of NAC genes based on their amino acid substitution rates was understood. Expression profiling against various stresses and phytohormones provides novel insights into specific and/or overlapping expression patterns of SiNAC genes, which may be responsible for functional divergence among individual members in this crop. Further, we performed structure modeling and molecular simulation of a stress-responsive protein, SiNAC128, proffering an initial framework for understanding its molecular function. Taken together, this genome-wide identification and expression profiling unlocks new avenues for systematic functional analysis of novel NAC gene family candidates which may be applied for improvising stress adaption in plants. PMID:23691254

Comprehensive genome-wide survey, genomic constitution and expression profiling of the NAC transcription factor family in foxtail millet (Setaria italica L.).

PubMed

Puranik, Swati; Sahu, Pranav Pankaj; Mandal, Sambhu Nath; B, Venkata Suresh; Parida, Swarup Kumar; Prasad, Manoj

2013-01-01

The NAC proteins represent a major plant-specific transcription factor family that has established enormously diverse roles in various plant processes. Aided by the availability of complete genomes, several members of this family have been identified in Arabidopsis, rice, soybean and poplar. However, no comprehensive investigation has been presented for the recently sequenced, naturally stress tolerant crop, Setaria italica (foxtail millet) that is famed as a model crop for bioenergy research. In this study, we identified 147 putative NAC domain-encoding genes from foxtail millet by systematic sequence analysis and physically mapped them onto nine chromosomes. Genomic organization suggested that inter-chromosomal duplications may have been responsible for expansion of this gene family in foxtail millet. Phylogenetically, they were arranged into 11 distinct sub-families (I-XI), with duplicated genes fitting into one cluster and possessing conserved motif compositions. Comparative mapping with other grass species revealed some orthologous relationships and chromosomal rearrangements including duplication, inversion and deletion of genes. The evolutionary significance as duplication and divergence of NAC genes based on their amino acid substitution rates was understood. Expression profiling against various stresses and phytohormones provides novel insights into specific and/or overlapping expression patterns of SiNAC genes, which may be responsible for functional divergence among individual members in this crop. Further, we performed structure modeling and molecular simulation of a stress-responsive protein, SiNAC128, proffering an initial framework for understanding its molecular function. Taken together, this genome-wide identification and expression profiling unlocks new avenues for systematic functional analysis of novel NAC gene family candidates which may be applied for improvising stress adaption in plants.

The Economics of Root Distributions of Terrestrial Biomes in Response to Elevated CO2

NASA Astrophysics Data System (ADS)

Lu, M.; Hedin, L. O. O.

2017-12-01

Belowground root distributions of terrestrial biomes are central to understanding soil biogeochemical processes and land carbon sink. Yet models are thus far not able to predict root distributions across plant functional groups and major biomes, limiting our ability to predict the response of land systems to elevated CO2 concentration. Of particular concern is the apparent lack of stimulation of the aboveground carbon sink despite 30% increase of atmospheric CO2 over the past half-century, and despite the clear acceleration of the land carbon sink over the same period. This apparent discrepancy in land ecosystem response has led to the proposition that changes in belowground root dynamics might be responsible for the overlooked land sink. We here present a new modeling approach for predicting the response of root biomass and soil carbon storage to increased CO2. Our approach considers the first-principle mechanisms and tradeoffs by which plants and plant roots invest carbon to gain belowground resources, in collaboration with distinct root symbioses. We allow plants to locally compete for nutrients, with the ability to allocate biomass at different depths in the soil profile. We parameterized our model using an unprecedented global dataset of root traits, and validated our biome-level predictions with a recently updated global root biomass database. Our results support the idea that plants "dig deeper" when exposed to increased CO2, and we offer an economic-based mechanism for predicting the plant root response across soil conditions, plant functional groups and major biomes. Our model also recreates the observed responses across a range of free-air CO2 enrichment experiments, including a distinct response between plants associated with ectomycorrhizal and arbuscular mycorrhizal fungi. Most broadly, our findings suggest that roots may be increasingly important in the land carbon sink, and call for a greater effort to quantify belowground responses to elevated atmospheric CO2.

Metabolomic Analysis of Alfalfa (Medicago sativa L.) Root-Symbiotic Rhizobia Responses under Alkali Stress.

PubMed

Song, Tingting; Xu, Huihui; Sun, Na; Jiang, Liu; Tian, Pu; Yong, Yueyuan; Yang, Weiwei; Cai, Hua; Cui, Guowen

2017-01-01

Alkaline salts (e.g., NaHCO 3 and Na 2 CO 3 ) causes more severe morphological and physiological damage to plants than neutral salts (e.g., NaCl and Na 2 SO 4 ) due to differences in pH. The mechanism by which plants respond to alkali stress is not fully understood, especially in plants having symbotic relationships such as alfalfa ( Medicago sativa L.). Therefore, a study was designed to evaluate the metabolic response of the root-nodule symbiosis in alfalfa under alkali stress using comparative metabolomics. Rhizobium-nodulized (RI group) and non-nodulized (NI group) alfalfa roots were treated with 200 mmol/L NaHCO 3 and, roots samples were analyzed for malondialdehydyde (MDA), proline, glutathione (GSH), superoxide dismutase (SOD), and peroxidase (POD) content. Additionally, metabolite profiling was conducted using gas chromatography combined with time-of-flight mass spectrometry (GC/TOF-MS). Phenotypically, the RI alfalfa exhibited a greater resistance to alkali stress than the NI plants examined. Physiological analysis and metabolic profiling revealed that RI plants accumulated more antioxidants (SOD, POD, GSH), osmolytes (sugar, glycols, proline), organic acids (succinic acid, fumaric acid, and alpha-ketoglutaric acid), and metabolites that are involved in nitrogen fixation. Our pairwise metabolomics comparisons revealed that RI alfalfa plants exhibited a distinct metabolic profile associated with alkali putative tolerance relative to NI alfalfa plants. Data provide new information about the relationship between non-nodulized, rhizobium-nodulized alfalfa and alkali resistance.

Metabolomic Analysis of Alfalfa (Medicago sativa L.) Root-Symbiotic Rhizobia Responses under Alkali Stress

PubMed Central

Song, Tingting; Xu, Huihui; Sun, Na; Jiang, Liu; Tian, Pu; Yong, Yueyuan; Yang, Weiwei; Cai, Hua; Cui, Guowen

2017-01-01

Alkaline salts (e.g., NaHCO3 and Na2CO3) causes more severe morphological and physiological damage to plants than neutral salts (e.g., NaCl and Na2SO4) due to differences in pH. The mechanism by which plants respond to alkali stress is not fully understood, especially in plants having symbotic relationships such as alfalfa (Medicago sativa L.). Therefore, a study was designed to evaluate the metabolic response of the root-nodule symbiosis in alfalfa under alkali stress using comparative metabolomics. Rhizobium-nodulized (RI group) and non-nodulized (NI group) alfalfa roots were treated with 200 mmol/L NaHCO3 and, roots samples were analyzed for malondialdehydyde (MDA), proline, glutathione (GSH), superoxide dismutase (SOD), and peroxidase (POD) content. Additionally, metabolite profiling was conducted using gas chromatography combined with time-of-flight mass spectrometry (GC/TOF-MS). Phenotypically, the RI alfalfa exhibited a greater resistance to alkali stress than the NI plants examined. Physiological analysis and metabolic profiling revealed that RI plants accumulated more antioxidants (SOD, POD, GSH), osmolytes (sugar, glycols, proline), organic acids (succinic acid, fumaric acid, and alpha-ketoglutaric acid), and metabolites that are involved in nitrogen fixation. Our pairwise metabolomics comparisons revealed that RI alfalfa plants exhibited a distinct metabolic profile associated with alkali putative tolerance relative to NI alfalfa plants. Data provide new information about the relationship between non-nodulized, rhizobium-nodulized alfalfa and alkali resistance. PMID:28744296

Genome-wide identification and expression profile analysis of the NAC transcription factor family during abiotic and biotic stress in woodland strawberry

PubMed Central

Qi, Yanxiang; Liu, Xiaomei; Pu, Jinji

2018-01-01

The NAC transcription factors involved plant development and response to various stress stimuli. However, little information is available concerning the NAC family in the woodland strawberry. Herein, 37 NAC genes were identified from the woodland strawberry genome and were classified into 13 groups based on phylogenetic analysis. And further analyses of gene structure and conserved motifs showed closer relationship of them in every subgroup. Quantitative real-time PCR evaluation different tissues revealed distinct spatial expression profiles of the FvNAC genes. The comprehensive expression of FvNAC genes revealed under abiotic stress (cold, heat, drought, salt), signal molecule treatments (H2O2, ABA, melatonin, rapamycin), biotic stress (Colletotrichum gloeosporioides and Ralstonia solanacearum). Expression profiles derived from quantitative real-time PCR suggested that 5 FvNAC genes responded dramatically to the various abiotic and biotic stresses, indicating their contribution to abiotic and biotic stresses resistance in woodland strawberry. Interestingly, FvNAC genes showed greater extent responded to the cold treatment than other abiotic stress, and H2O2 exhibited a greater response than ABA, melatonin, and rapamycin. For biotic stresses, 3 FvNAC genes were up-regulated during infection with C. gloeosporioides, while 6 FvNAC genes were down-regulated during infection with R. solanacearum. In conclusion, this study identified candidate FvNAC genes to be used for the genetic improvement of abiotic and biotic stress tolerance in woodland strawberry. PMID:29897926

Modulation of antimicrobial metabolites production by the fungus Aspergillus parasiticus

PubMed Central

Bracarense, Adriana A.P.; Takahashi, Jacqueline A.

2014-01-01

Biosynthesis of active secondary metabolites by fungi occurs as a specific response to the different growing environments. Changes in this environment alter the chemical and biological profiles leading to metabolites diversification and consequently to novel pharmacological applications. In this work, it was studied the influence of three parameters (fermentation length, medium composition and aeration) in the biosyntheses of antimicrobial metabolites by the fungus Aspergillus parasiticus in 10 distinct fermentation periods. Metabolism modulation in two culturing media, CYA and YES was evaluated by a 22 full factorial planning (ANOVA) and on a 23 factorial planning, role of aeration, medium composition and carbohydrate concentration were also evaluated. In overall, 120 different extracts were prepared, their HPLC profiles were obtained and the antimicrobial activity against A. flavus, C. albicans, E. coli and S. aureus of all extracts was evaluated by microdilution bioassay. Yield of kojic acid, a fine chemical produced by the fungus A. parasiticus was determined in all extracts. Statistical analyses pointed thirteen conditions able to modulate the production of bioactive metabolites by A. parasiticus. Effect of carbon source in metabolites diversification was significant as shown by the changes in the HPLC profiles of the extracts. Most of the extracts presented inhibition rates higher than that of kojic acid as for the extract obtained after 6 days of fermentation in YES medium under stirring. Kojic acid was not the only metabolite responsible for the activity since some highly active extracts showed to possess low amounts of this compound, as determined by HPLC. PMID:24948950

Stream bed temperature profiles as indicators of percolation characteristics beneath arroyos in the middle Rio Grande Basin, USA

USGS Publications Warehouse

Constantz, J.; Thomas, C.L.

1997-01-01

Stream bed temperature profiles were monitored continuously during water year 1990 and 1991 (WY90 and 91) in two New Mexico arroyos, similar in their meteorological features and dissimilar in their hydrological features. Stream bed temperature profiles between depths of 30 and 300 cm were examined to determine whether temporal changes in temperature profiles represent accurate indicators of the timing, depth and duration of percolation in each stream bed. These results were compared with stream flow, air temperature, and precipitation records for WY90 and 91, to evaluate the effect of changing surface conditions on temperature profiles. Temperature profiles indicate a persistently high thermal gradient with depth beneath Grantline Arroyo, except during a semi-annual thermal reversal in spring and autumn. This typifies the thermal response of dry sediments with low thermal conductivities. High thermal gradients were disrupted only during infrequent stream flows, followed by rapid re-establishment of high gradients. The stream bed temperature at 300 cm was unresponsive to individual precipitation or stream flow during WY90 and 91. This thermal pattern provides strong evidence that most seepage into Grantline Arroyo failed to percolate at a sufficient rate to reach 300 cm before being returned to the atmosphere. A distinctly different thermal pattern was recorded beneath Tijeras Arroyo. Low thermal gradients between 30 and 300 cm and large diurnal variations in temperature, suggest that stream flow created continuous, advection-dominated heat transport for over 300 days, annually. Beneath Tijeras Arroyo, low thermal gradients were interrupted only briefly during periodic, dry summer conditions. Comparisons of stream flow records for WY90 and 91 with stream bed temperature profiles indicate that independent analysis of thermal patterns provides accurate estimates of the timing, depth and duration of percolation beneath both arroyos. Stream flow loss estimates indicate that seepage rates were 15 times greater for Tijeras Arroyo than for Grantline Arroyo, which supports qualitative conclusions derived from analysis of stream bed temperature responses to surface conditions. ?? 1997 John Wiley & Sons, Ltd.

Profiling medical school learning environments in Malaysia: a validation study of the Johns Hopkins Learning Environment Scale.

PubMed

Tackett, Sean; Bakar, Hamidah Abu; Shilkofski, Nicole A; Coady, Niamh; Rampal, Krishna; Wright, Scott

2015-01-01

While a strong learning environment is critical to medical student education, the assessment of medical school learning environments has confounded researchers. Our goal was to assess the validity and utility of the Johns Hopkins Learning Environment Scale (JHLES) for preclinical students at three Malaysian medical schools with distinct educational and institutional models. Two schools were new international partnerships, and the third was school leaver program established without international partnership. First- and second-year students responded anonymously to surveys at the end of the academic year. The surveys included the JHLES, a 28-item survey using five-point Likert scale response options, the Dundee Ready Educational Environment Measure (DREEM), the most widely used method to assess learning environments internationally, a personal growth scale, and single-item global learning environment assessment variables. The overall response rate was 369/429 (86%). After adjusting for the medical school year, gender, and ethnicity of the respondents, the JHLES detected differences across institutions in four out of seven domains (57%), with each school having a unique domain profile. The DREEM detected differences in one out of five categories (20%). The JHLES was more strongly correlated than the DREEM to two thirds of the single-item variables and the personal growth scale. The JHLES showed high internal reliability for the total score (α=0.92) and the seven domains (α, 0.56-0.85). The JHLES detected variation between learning environment domains across three educational settings, thereby creating unique learning environment profiles. Interpretation of these profiles may allow schools to understand how they are currently supporting trainees and identify areas needing attention.

Molecular and cellular characterization of a Salmonella enterica serovar Paratyphi a outbreak strain and the human immune response to infection.

PubMed

Gal-Mor, Ohad; Suez, Jotham; Elhadad, Dana; Porwollik, Steffen; Leshem, Eyal; Valinsky, Lea; McClelland, Michael; Schwartz, Eliezer; Rahav, Galia

2012-02-01

Enteric fever is an invasive life-threatening systemic disease caused by the Salmonella enterica human-adapted serovars Typhi and Paratyphi. Increasing incidence of infections with Salmonella enterica serovar Paratyphi A and the spreading of its antibiotic-resistant derivates pose a significant health concern in some areas of the world. Herein, we describe a molecular and phenotypic characterization of an S. Paratyphi A strain accounted for a recent paratyphoid outbreak in Nepal that affected at least 37 travelers. Pulsed-field gel electrophoresis analysis of the outbreak isolates revealed one genetic clone (pulsotype), confirming a single infecting source. Genetic profiling of the outbreak strain demonstrated the contribution of specific bacteriophages as a prime source of genetic diversity among clinical isolates of S. Paratyphi A. Phenotypic characterization in comparison with the S. Paratyphi A ATCC 9150 reference sequenced strain showed differences in flagellar morphology and increased abilities of the outbreak strain with respect to its motility, invasion into nonphagocytic cells, intracellular multiplication, survival within macrophages, and higher induction of interleukin-8 (IL-8) secreted by host cells. Collectively, these differences suggest an enhanced virulence potential of this strain and demonstrate an interesting phenotypic variation among S. Paratyphi A isolates. In vivo profiling of 16 inflammatory cytokines in patients infected with the outbreak strain revealed a common profile of a remarkable gamma interferon (IFN-γ) induction together with elevated concentrations of tumor necrosis factor alpha (TNF-α), IL-6, IL-8, IL-10, and IL-15, but not IL-12, which was previously demonstrated as elevated in nontyphoidal Salmonella infections. This apparent profile implies a distinct immune response to paratyphoid infections.

Profiling medical school learning environments in Malaysia: a validation study of the Johns Hopkins Learning Environment Scale

PubMed Central

Tackett, Sean; Bakar, Hamidah Abu; Shilkofski, Nicole A.; Coady, Niamh; Rampal, Krishna; Wright, Scott

2015-01-01

Purpose: While a strong learning environment is critical to medical student education, the assessment of medical school learning environments has confounded researchers. Our goal was to assess the validity and utility of the Johns Hopkins Learning Environment Scale (JHLES) for preclinical students at three Malaysian medical schools with distinct educational and institutional models. Two schools were new international partnerships, and the third was school leaver program established without international partnership. Methods: First- and second-year students responded anonymously to surveys at the end of the academic year. The surveys included the JHLES, a 28-item survey using five-point Likert scale response options, the Dundee Ready Educational Environment Measure (DREEM), the most widely used method to assess learning environments internationally, a personal growth scale, and single-item global learning environment assessment variables. Results: The overall response rate was 369/429 (86%). After adjusting for the medical school year, gender, and ethnicity of the respondents, the JHLES detected differences across institutions in four out of seven domains (57%), with each school having a unique domain profile. The DREEM detected differences in one out of five categories (20%). The JHLES was more strongly correlated than the DREEM to two thirds of the single-item variables and the personal growth scale. The JHLES showed high internal reliability for the total score (α=0.92) and the seven domains (α, 0.56-0.85). Conclusion: The JHLES detected variation between learning environment domains across three educational settings, thereby creating unique learning environment profiles. Interpretation of these profiles may allow schools to understand how they are currently supporting trainees and identify areas needing attention. PMID:26165949

Distinct health behavior and psychosocial profiles of young adult survivors of childhood cancers: a mixed methods study.

PubMed

Lowe, Kincaid; Escoffery, Cam; Mertens, Ann C; Berg, Carla J

2016-08-01

We used a mixed-methods approach to examine health behavior profiles of young adult cancer survivors and characterize related sociodemographic and psychosocial factors. We conducted a mail-based survey assessing sociodemographics, cancer treatment, health behaviors (e.g., tobacco use, physical activity), healthcare provider interactions, and psychosocial factors (e.g., Profile of Moods States [POMS]) among 106 young adult survivors from a southeastern cancer center and semi-structured interviews among a subset of 26. A k-means cluster analysis using eight health behaviors yielded three distinct health behavior profiles: high risk (n = 25), moderate risk (n = 39), and low risk (n = 40). High risks had the highest current alcohol, tobacco, and marijuana use; physical activity; and number of sexual partners (p's < 0.001). They had higher symptoms of POMS tension-anxiety, depression-dejection, fatigue-inertia, and confusion-bewilderment (p's < 0.05). Moderate risks had lowest physical activity (p < 0.05) but otherwise had moderate health behaviors. Low risks had the lowest alcohol, tobacco, and marijuana use and fewest sexual partners (p's < 0.05). They had the lowest levels of tension-anxiety, depression-dejection, fatigue-inertia, and confusion-bewilderment (p's < 0.05). Qualitative interviews showed that cancer had a range of effects on health behaviors and variable experiences regarding how healthcare providers address these behaviors. Assessing health behavior profiles, rather than individual health behaviors, is informative in characterizing young adult cancer survivors and targeting survivorship care. Young adult cancer survivors demonstrate distinct health behavior profiles and are differentially impacted by the experience of cancer. Healthcare providers should be consistently intervening to ensure that survivors understand their specific health risks.

Clustering of self-organizing map identifies five distinct medulloblastoma subgroups.

PubMed

Cao, Changjun; Wang, Wei; Jiang, Pucha

2016-01-01

Medulloblastoma is one the most malignant paediatric brain tumours. Molecular subgrouping these medulloblastomas will not only help identify specific cohorts for certain treatment but also improve confidence in prognostic prediction. Currently, there is a consensus of the existences of four distinct subtypes of medulloblastoma. We proposed a novel bioinformatics method, clustering of self-organizing map, to determine the subgroups and their molecular diversity. Microarray expression profiles of 46 medulloblastoma samples were analysed and five clusters with distinct demographics, clinical outcome and transcriptional profiles were identified. The previously reported Wnt subgroup was identified as expected. Three other novel subgroups were proposed for later investigation. Our findings underscore the value of SOM clustering for discovering the medulloblastoma subgroups. When the suggested subdivision has been confirmed in large cohorts, this method should serve as a part of routine classification of clinical samples.

Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer

PubMed Central

Shen, Lanlan; Toyota, Minoru; Kondo, Yutaka; Lin, E; Zhang, Li; Guo, Yi; Hernandez, Natalie Supunpong; Chen, Xinli; Ahmed, Saira; Konishi, Kazuo; Hamilton, Stanley R.; Issa, Jean-Pierre J.

2007-01-01

Colon cancer has been viewed as the result of progressive accumulation of genetic and epigenetic abnormalities. However, this view does not fully reflect the molecular heterogeneity of the disease. We have analyzed both genetic (mutations of BRAF, KRAS, and p53 and microsatellite instability) and epigenetic alterations (DNA methylation of 27 CpG island promoter regions) in 97 primary colorectal cancer patients. Two clustering analyses on the basis of either epigenetic profiling or a combination of genetic and epigenetic profiling were performed to identify subclasses with distinct molecular signatures. Unsupervised hierarchical clustering of the DNA methylation data identified three distinct groups of colon cancers named CpG island methylator phenotype (CIMP) 1, CIMP2, and CIMP negative. Genetically, these three groups correspond to very distinct profiles. CIMP1 are characterized by MSI (80%) and BRAF mutations (53%) and rare KRAS and p53 mutations (16% and 11%, respectively). CIMP2 is associated with 92% KRAS mutations and rare MSI, BRAF, or p53 mutations (0, 4, and 31% respectively). CIMP-negative cases have a high rate of p53 mutations (71%) and lower rates of MSI (12%) or mutations of BRAF (2%) or KRAS (33%). Clustering based on both genetic and epigenetic parameters also identifies three distinct (and homogeneous) groups that largely overlap with the previous classification. The three groups are independent of age, gender, or stage, but CIMP1 and 2 are more common in proximal tumors. Together, our integrated genetic and epigenetic analysis reveals that colon cancers correspond to three molecularly distinct subclasses of disease. PMID:18003927

Physiological and transcriptional responses to high temperature in Arthrospira (Spirulina) platensis C1.

PubMed

Panyakampol, Jaruta; Cheevadhanarak, Supapon; Sutheeworapong, Sawannee; Chaijaruwanich, Jeerayut; Senachak, Jittisak; Siangdung, Wipawan; Jeamton, Wattana; Tanticharoen, Morakot; Paithoonrangsarid, Kalyanee

2015-03-01

Arthrospira (Spirulina) platensis is a well-known commercial cyanobacterium that is used as a food and in feed supplements. In this study, we examined the physiological changes and whole-genome expression in A. platensis C1 exposed to high temperature. We found that photosynthetic activity was significantly decreased after the temperature was shifted from 35°C to 42°C for 2 h. A reduction in biomass production and protein content, concomitant with the accumulation of carbohydrate content, was observed after prolonged exposure to high temperatures for 24 h. Moreover, the results of the expression profiling in response to high temperature at the designated time points (8 h) revealed two distinct phases of the responses. The first was the immediate response phase, in which the transcript levels of genes involved in different mechanisms, including genes for heat shock proteins; genes involved in signal transduction and carbon and nitrogen metabolism; and genes encoding inorganic ion transporters for magnesium, nitrite and nitrate, were either transiently induced or repressed by the high temperature. In the second phase, the long-term response phase, both the induction and repression of the expression of genes with important roles in translation and photosynthesis were observed. Taken together, the results of our physiological and transcriptional studies suggest that dynamic changes in the transcriptional profiles of these thermal-responsive genes might play a role in maintaining cell homeostasis under high temperatures, as reflected in the growth and biochemical composition, particularly the protein and carbohydrate content, of A. platensis C1. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.

PubMed

Chen, Chen-Wen; Chen, Qian-Bo; Ouyang, Qing; Sun, Ji-Hu; Liu, Fang-Ting; Song, Dian-Wen; Yuan, Hong-Bin

2012-06-25

Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1 β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

Regret as Autobiographical Memory

ERIC Educational Resources Information Center

Davison, Ian M.; Feeney, Aidan

2008-01-01

We apply an autobiographical memory framework to the study of regret. Focusing on the distinction between regrets for specific and general events we argue that the temporal profile of regret, usually explained in terms of the action-inaction distinction, is predicted by models of autobiographical memory. In two studies involving participants in…

Neurobiological correlates of distinct post-traumatic stress disorder symptom profiles during threat anticipation in combat veterans.

PubMed

Grupe, D W; Wielgosz, J; Davidson, R J; Nitschke, J B

2016-07-01

Previous research in post-traumatic stress disorder (PTSD) has identified disrupted ventromedial prefrontal cortex (vmPFC) function in those with v. without PTSD. It is unclear whether this brain region is uniformly affected in all individuals with PTSD, or whether vmPFC dysfunction is related to individual differences in discrete features of this heterogeneous disorder. In a sample of 51 male veterans of Operation Enduring Freedom/Operation Iraqi Freedom, we collected functional magnetic resonance imaging data during a novel threat anticipation task with crossed factors of threat condition and temporal unpredictability. Voxelwise regression analyses related anticipatory brain activation to individual differences in overall PTSD symptom severity, as well as individual differences in discrete symptom subscales (re-experiencing, emotional numbing/avoidance, and hyperarousal). The vmPFC showed greater anticipatory responses for safety relative to threat, driven primarily by deactivation during threat anticipation. During unpredictable threat anticipation, increased PTSD symptoms were associated with relatively greater activation for threat v. However, simultaneous regression on individual symptom subscales demonstrated that this effect was driven specifically by individual differences in hyperarousal symptoms. Furthermore, this analysis revealed an additional, anatomically distinct region of the vmPFC in which re-experiencing symptoms were associated with greater activation during threat anticipation. Increased anticipatory responses to unpredictable threat in distinct vmPFC subregions were uniquely associated with elevated hyperarousal and re-experiencing symptoms in combat veterans. These results underscore the disruptive impact of uncertainty for veterans, and suggest that investigating individual differences in discrete aspects of PTSD may advance our understanding of underlying neurobiological mechanisms.

Lung-resident eosinophils represent a distinct regulatory eosinophil subset

PubMed Central

Mesnil, Claire; Raulier, Stéfanie; Paulissen, Geneviève; Xiao, Xue; Birrell, Mark A.; Pirottin, Dimitri; Janss, Thibaut; Henket, Monique; Schleich, Florence N.; Radermecker, Marc; Thielemans, Kris; Gillet, Laurent; Thiry, Marc; Belvisi, Maria G.; Louis, Renaud; Desmet, Christophe; Bureau, Fabrice

2016-01-01

Increases in eosinophil numbers are associated with infection and allergic diseases, including asthma, but there is also evidence that eosinophils contribute to homeostatic immune processes. In mice, the normal lung contains resident eosinophils (rEos), but their function has not been characterized. Here, we have reported that steady-state pulmonary rEos are IL-5–independent parenchymal Siglec-FintCD62L+CD101lo cells with a ring-shaped nucleus. During house dust mite–induced airway allergy, rEos features remained unchanged, and rEos were accompanied by recruited inflammatory eosinophils (iEos), which were defined as IL-5–dependent peribronchial Siglec-FhiCD62L–CD101hi cells with a segmented nucleus. Gene expression analyses revealed a more regulatory profile for rEos than for iEos, and correspondingly, mice lacking lung rEos showed an increase in Th2 cell responses to inhaled allergens. Such elevation of Th2 responses was linked to the ability of rEos, but not iEos, to inhibit the maturation, and therefore the pro-Th2 function, of allergen-loaded DCs. Finally, we determined that the parenchymal rEos found in nonasthmatic human lungs (Siglec-8+CD62L+IL-3Rlo cells) were phenotypically distinct from the iEos isolated from the sputa of eosinophilic asthmatic patients (Siglec-8+CD62LloIL-3Rhi cells), suggesting that our findings in mice are relevant to humans. In conclusion, our data define lung rEos as a distinct eosinophil subset with key homeostatic functions. PMID:27548519

Macrophage Heterogeneity and Plasticity: Impact of Macrophage Biomarkers on Atherosclerosis

PubMed Central

Martínez, María Sofía; Palmar, Jim; Bautista, Jordan; Chávez-Castillo, Mervin; Gómez, Alexis; Bermúdez, Valmore

2015-01-01

Cardiovascular disease (CVD) is a global epidemic, currently representing the worldwide leading cause of morbidity and mortality. Atherosclerosis is the fundamental pathophysiologic component of CVD, where the immune system plays an essential role. Monocytes and macrophages are key mediators in this aspect: due to their heterogeneity and plasticity, these cells may act as either pro- or anti-inflammatory mediators. Indeed, monocytes may develop heterogeneous functional phenotypes depending on the predominating pro- or anti-inflammatory microenvironment within the lesion, resulting in classic, intermediate, and non-classic monocytes, each with strikingly differing features. Similarly, macrophages may also adopt heterogeneous profiles being mainly M1 and M2, the former showing a proinflammatory profile while the latter demonstrates anti-inflammatory traits; they are further subdivided in several subtypes with more specialized functions. Furthermore, macrophages may display plasticity by dynamically shifting between phenotypes in response to specific signals. Each of these distinct cell profiles is associated with diverse biomarkers which may be exploited for therapeutic intervention, including IL-10, IL-13, PPAR-γ, LXR, NLRP3 inflammasomes, and microRNAs. Direct modulation of the molecular pathways concerning these potential macrophage-related targets represents a promising field for new therapeutic alternatives in atherosclerosis and CVD. PMID:26491604

Interactions between ifenprodil and dizocilpine on mouse behaviour in models of anxiety and working memory.

PubMed

Fraser, C M; Cooke, M J; Fisher, A; Thompson, I D; Stone, T W

1996-11-01

The N-methyl-D-aspartate (NMDA) receptor polyamine site antagonist, ifenprodil, had no effect on spontaneous alteration or locomotor activity in the Y-maze when given alone. The NMDA receptor/ion channel blocker, dizocilpine, induced a deficit in spontaneous alteration, but when ifenprodil was co-administered with dizocilpine, it showed a strong tendency to attenuate the dizocilpine-induced deficit. In the plus-maze, ifenprodil had an anxiolytic profile which was accompanied by an increase in locomotion. Dizocilpine had an anxiolytic profile in this model and increased locomotor activity. When co-administered with dizocilpine, ifenprodil reduced both the anxiolytic and locomotor effects of dizocilpine. When co-administered with ifenprodil, cyclopentyladenosine (CPA) and 1,3-dipropyl-8-cyclopentylxanthine (CPX) reduced the anxiolytic effect of ifenprodil. CPA and CPX in combination did not reverse the anxiolytic effect of ifenpropil. It is concluded that NMDA antagonists with different sites of action can show distinct behavioural profiles, with dizocilpine but not ifenprodil inducing a deficit in working memory, while both are anxiolytic. Blockade of NMDA receptors by ifenprodil, however, can preclude any response to dizocilpine. The anxiolytic activity of ifenprodil may involve the release of purines acting at adenosine receptors.

New perspectives on CKD-induced dyslipidemia.

PubMed

Bermúdez-López, Marcelino; Arroyo, David; Betriu, Àngels; Masana, Luis; Fernández, Elvira; Valdivielso, Jose M

2017-10-01

Chronic kidney disease (CKD) is a world-wide health concern associated with a significantly higher cardiovascular morbidity and mortality. One of the principal cardiovascular risk factors is the lipid profile. CKD patients have a more frequent and progressive atheromatous disease that cannot be explained by the classical lipid parameters used in the daily clinical practice. Areas covered: The current review summarizes prevailing knowledge on the role of lipids in atheromathosis in CKD patients, including an overview of lipoprotein metabolism highlighting the CKD-induced alterations. Moreover, to obtain information beyond traditional lipid parameters, new state-of-the-art technologies such as lipoprotein subfraction profiling and lipidomics are also reviewed. Finally, we analyse the potential of new lipoprotein subclasses as therapeutic targets in CKD. Expert opinion: The CKD-induced lipid profile has specific features distinct from the general population. Besides quantitative alterations, renal patients have a plethora of qualitative lipid alterations that cannot be detected by routine determinations and are responsible for the excess of cardiovascular risk. New parameters, such as lipoprotein particle number and size, together with new biomarkers obtained by lipidomics will personalize the management of these patients. Therefore, nephrologists need to be aware of new insights into lipoprotein metabolism to improve cardiovascular risk assessment.

Mycobacterium tuberculosis RsdA provides a conformational rationale for selective regulation of σ-factor activity by proteolysis

PubMed Central

Jaiswal, Ravi K.; Prabha, Tangirala Surya; Manjeera, Gowravaram; Gopal, Balasubramanian

2013-01-01

The relative levels of different σ factors dictate the expression profile of a bacterium. Extracytoplasmic function σ factors synchronize the transcriptional profile with environmental conditions. The cellular concentration of free extracytoplasmic function σ factors is regulated by the localization of this protein in a σ/anti-σ complex. Anti-σ factors are multi-domain proteins with a receptor to sense environmental stimuli and a conserved anti-σ domain (ASD) that binds a σ factor. Here we describe the structure of Mycobacterium tuberculosis anti-σD (RsdA) in complex with the -35 promoter binding domain of σD (σD4). We note distinct conformational features that enable the release of σD by the selective proteolysis of the ASD in RsdA. The structural and biochemical features of the σD/RsdA complex provide a basis to reconcile diverse regulatory mechanisms that govern σ/anti-σ interactions despite high overall structural similarity. Multiple regulatory mechanisms embedded in an ASD scaffold thus provide an elegant route to rapidly re-engineer the expression profile of a bacterium in response to an environmental stimulus. PMID:23314154

Genome-wide analysis reveals inositol, not choline, as the major effector of Ino2p-Ino4p and unfolded protein response target gene expression in yeast.

PubMed

Jesch, Stephen A; Zhao, Xin; Wells, Martin T; Henry, Susan A

2005-03-11

In the yeast Saccharomyces cerevisiae, the transcription of many genes encoding enzymes of phospholipid biosynthesis are repressed in cells grown in the presence of the phospholipid precursors inositol and choline. A genome-wide approach using cDNA microarray technology was used to profile the changes in the expression of all genes in yeast that respond to the exogenous presence of inositol and choline. We report that the global response to inositol is completely distinct from the effect of choline. Whereas the effect of inositol on gene expression was primarily repressing, the effect of choline on gene expression was activating. Moreover, the combination of inositol and choline increased the number of repressed genes compared with inositol alone and enhanced the repression levels of a subset of genes that responded to inositol. In all, 110 genes were repressed in the presence of inositol and choline. Two distinct sets of genes exhibited differential expression in response to inositol or the combination of inositol and choline in wild-type cells. One set of genes contained the UASINO sequence and were bound by Ino2p and Ino4p. Many of these genes were also negatively regulated by OPI1, suggesting a common regulatory mechanism for Ino2p, Ino4p, and Opi1p. Another nonoverlapping set of genes was coregulated by the unfolded protein response pathway, an ER-localized stress response pathway, but was not dependent on OPI1 and did not show further repression when choline was present together with inositol. These results suggest that inositol is the major effector of target gene expression, whereas choline plays a minor role.

Genome Wide Analysis Reveals Inositol, not Choline, as the Major Effector of Ino2p-Ino4p and Unfolded Protein Response Target Gene Expression in Yeast

PubMed Central

Jesch, Stephen A.; Zhao, Xin; Wells, Martin T.; Henry, Susan A.

2005-01-01

SUMMARY In the yeast Saccharomyces cerevisiae the transcription of many genes encoding enzymes of phospholipid biosynthesis are repressed in cells grown in the presence of the phospholipid precursors inositol and choline. A genome-wide approach using cDNA microarray technology was utilized to profile the changes in the expression of all genes in yeast that respond to the exogenous presence of inositol and choline. We report that the global response to inositol is completely distinct from the effect of choline. Whereas the effect of inositol on gene expression was primarily repressing, the effect of choline on gene expression was activating. Moreover, the combination inositol and choline increased the number of repressed genes compared to inositol alone and enhanced the repression levels of a subset of genes that responded to inositol. In all, 110 genes were repressed in the presence of inositol and choline. Two distinct sets of genes exhibited differential expression in response to inositol or the combination of inositol and choline in wild type cells. One set of genes contained the UASINO sequence and were bound by Ino2p and Ino4p. Many of these genes were also negatively regulated by OPI1, suggesting a common regulatory mechanism for Ino2p, Ino4p, and Opi1p. Another non-overlapping set of genes were coregulated by the unfolded protein response pathway, an ER-localized stress response pathway, but were not dependent on OPI1 and did not show further repression when choline was present together with inositol. These results suggest that inositol is the major effector of target gene expression, while choline plays a minor role. PMID:15611057

The conditioning and extinction of fear in youths: What’s sex got to do with it?

PubMed Central

Chauret, Mélissa; La Buissonnière-Ariza, Valérie; Tremblay, Vickie Lamoureux; Suffren, Sabrina; Servonnet, Alice; Pine, Daniel S.; Maheu, Françoise S.

2015-01-01

Adult work shows differences in emotional processing influenced by sexes of both the viewer and expresser of facial expressions. We investigated this in 120 healthy youths (57 boys; 10–17 years old) randomly assigned to fear conditioning and extinction tasks using either neutral male or female faces as the conditioned threat and safety cues, and a fearful face paired with a shrieking scream as the unconditioned stimulus. Fear ratings and skin conductance responses (SCRs) were assessed. Male faces triggered increased fear ratings in all participants during conditioning and extinction. Greater differential SCRs were observed in boys viewing male faces and in girls viewing female faces during conditioning. During extinction, differential SCR findings remained significant in boys viewing male faces. Our findings demonstrate how sex of participant and sex of target interact to shape fear responses in youths, and how the type of measure may lead to distinct profiles of fear responses. PMID:24929048

A multiplexed single-cell CRISPR screening platform enables systematic dissection of the unfolded protein response

PubMed Central

Adamson, Britt; Norman, Thomas M.; Jost, Marco; Cho, Min Y.; Nuñez, James K.; Chen, Yuwen; Villalta, Jacqueline E.; Gilbert, Luke A.; Horlbeck, Max A.; Hein, Marco Y.; Pak, Ryan A.; Gray, Andrew N.; Gross, Carol A.; Dixit, Atray; Parnas, Oren; Regev, Aviv; Weissman, Jonathan S.

2016-01-01

SUMMARY Functional genomics efforts face tradeoffs between number of perturbations examined and complexity of phenotypes measured. We bridge this gap with Perturb-seq, which combines droplet-based single-cell RNA-seq with a strategy for barcoding CRISPR-mediated perturbations, allowing many perturbations to be profiled in pooled format. We applied Perturb-seq to dissect the mammalian unfolded protein response (UPR) using single and combinatorial CRISPR perturbations. Two genome-scale CRISPR interference (CRISPRi) screens identified genes whose repression perturbs ER homeostasis. Subjecting ~100 hits to Perturb-seq enabled high-precision functional clustering of genes. Single-cell analyses decoupled the three UPR branches, revealed bifurcated UPR branch activation among cells subject to the same perturbation, and uncovered differential activation of the branches across hits, including an isolated feedback loop between the translocon and IRE1α. These studies provide insight into how the three sensors of ER homeostasis monitor distinct types of stress and highlight the ability of Perturb-seq to dissect complex cellular responses. PMID:27984733

Staff nurse commitment, work relationships, and turnover intentions: a latent profile analysis.

PubMed

Gellatly, Ian R; Cowden, Tracy L; Cummings, Greta G

2014-01-01

The three-component model of organization commitment has typically been studied using a variable-centered rather than a person-centered approach, preventing a more complete understanding of how these forms of commitment are felt and expressed as a whole. Latent profile analysis was used to identify qualitatively distinct categories or profiles of staff nurses' commitment. Then, associations of the profiles with perceived work unit relations and turnover intentions were examined. Three hundred thirty-six registered nurses provided data on affective, normative, and continuance commitment, perceived work unit relations, and turnover intentions. Latent profile analysis of the nurses' commitment scores revealed six distinct profile groups. Work unit relations and turnover intentions were compared in the six profile-defined groups. Staff nurses with profiles characterized by high affective commitment and/or high normative commitment in relation to other components experienced stronger work unit relations and reported lower turnover intentions. Profiles characterized by high continuance commitment relative to other components or by low overall commitment experienced poorer work unit relations, and the turnover risk was higher. High continuance commitment in combination with high affective and normative commitment was experienced differently than high continuance commitment in combination with low affective and normative commitment. Healthcare organizations often foster commitment by using continuance commitment-enhancing strategies (e.g., offer high salaries and attractive benefits) that may inadvertently introduce behavioral risk. This work suggests the importance of changing the context in which continuance commitment occurs by strengthening the other two components.

Within treatment therapeutic alliance ratings profiles predict posttreatment frequency of alcohol use

PubMed Central

Prince, Mark A.; Connors, Gerard J.; Maisto, Stephen A.; Dearing, Ronda L.

2016-01-01

While past research has demonstrated a positive relationship between the therapeutic alliance (TA) and improved drinking outcomes, specific aspects of the alliance have received less attention. In this study, we examined the association between alliance characteristics during treatment and 4-month follow-up drinking reports. 65 treatment-seeking alcohol dependent clients who participated in 12 weeks of individual outpatient treatment provided weekly TA ratings during treatment and reported on pre-treatment, during treatment, and post-treatment alcohol use. Latent profile analysis was conducted to discern distinct profiles of client and therapist ratings of therapeutic alliance with similar alliance characteristics. TA profiles were based on clients’ and therapists’ mean alliance rating, minimum alliance rating, maximum alliance rating, the range of alliance ratings, and the difference in session number between maximum and minimum alliance ratings. 1- through 4- class models were fit to the data. Model fit was judged by comparative fit indices, substantive interpretability, and parsimony. Wald tests of mean equality determined whether classes differed on follow-up percentage of days abstinent (PDA) at 4 months posttreatment. 3-profile solutions provided the best fit for both client and therapist ratings of the therapeutic alliance. Client alliance rating profiles predicted drinking in the follow-up period, but therapist rating profiles did not. These results suggest that distinct profiles of the therapeutic alliance can be identified and that client alliance rating profiles are associated with frequency of alcohol use following outpatient treatment. PMID:26999350

[Characteristics of catatonia in schizophrenia and mood disorders].

PubMed

van den Ameele, S; Sabbe, B; Morrens, M

2015-01-01

Catatonia is a psychomotor symptom cluster that co-occurs with schizophrenia and with mood disorders. The characterisation and the differentiation of psychomotor symptom clusters can contribute to a more accurate diagnosis and a better understanding of underlying neurobiological processes. To compare epidemiology, clinical presentation and treatment of catatonia in schizophrenia and in mood disorders. We reviewed the literature using PubMed. Catatonia is highly prevalent in both schizophrenia and mood disorders, but is slightly more prevalent in the latter. In spite of a considerable overlap, there are differentiating trends in the catatonic symptom profile of schizophrenia and mood disorders. In both of these disorders catatonia is a marker for increasing severity of the course of the illness. Compared to catatonia in mood disorders, catatonia in schizophrenia has a poorer response to benzodiazepines and ECT. Catatonia in schizophrenia and mood disorders is characterized by a distinctive profile. Comparative research on clinical presentation and neurobiological processes is warranted in order to arrive at a more accurate characterisation of these psychomotor symptom clusters.

[Functional selectivity of opioid receptors ligands].

PubMed

Audet, Nicolas; Archer-Lahlou, Elodie; Richard-Lalonde, Mélissa; Piñeyro-Filpo, Graciela

2010-01-01

Opiates are the most effective analgesics available for the treatment of severe pain. However, their clinical use is restricted by unwanted side effects such as tolerance, physical dependence and respiratory depression. The strategy to develop new opiates with reduced side effects has mainly focused on the study and production of ligands that specifically bind to different opiate receptors subtypes. However, this strategy has not allowed the production of novel therapeutic ligands with a better side effects profile. Thus, other research strategies need to be explored. One which is receiving increasing attention is the possibility of exploiting ligand ability to stabilize different receptor conformations with distinct signalling profiles. This newly described property, termed functional selectivity, provides a potential means of directing the stimulus generated by an activated receptor towards a specific cellular response. Here we summarize evidence supporting the existence of ligand-specific active conformations for two opioid receptors subtypes (delta and mu), and analyze how functional selectivity may contribute in the production of longer lasting, better tolerated opiate analgesics. double dagger.

Fiber-utilizing capacity varies in Prevotella- versus Bacteroides-dominated gut microbiota.

PubMed

Chen, Tingting; Long, Wenmin; Zhang, Chenhong; Liu, Shuang; Zhao, Liping; Hamaker, Bruce R

2017-06-01

The gut microbiota of individuals are dominated by different fiber-utilizing bacteria, which ferment dietary fiber into short chain fatty acids (SCFAs) known to be important for human health. Here, we show that the dominance of Prevotella versus Bacteroides in fecal innocula, identified into two different enterotypes, differentially impacts in vitro fermentation profiles of SCFAs from fibers with different chemical structures. In a microbiome of the Prevotella enterotype, fructooligosaccharides, and sorghum and corn arabinoxylans significantly promoted one single Prevotella OTU with equally high production of total SCFAs with propionate as the major product. Conversely, in the Bacteroides-dominated microbiota, the three fibers enriched different OTUs leading to different levels and ratios of SCFAs. This is the first report showing how individual differences in two enterotypes cause distinctly different responses to dietary fiber. Microbiota dominated by different fiber-utilizing bacteria may impact host health by way of producing different amounts and profiles of SCFAs from the same carbohydrate substrates.

Distinct Retinal Capillary Plexuses in Normal Eyes as Observed in Optical Coherence Tomography Angiography Axial Profile Analysis.

PubMed

Hirano, Takao; Chanwimol, Karntida; Weichsel, Julian; Tepelus, Tudor; Sadda, Srinivas

2018-06-20

Optical coherence tomography angiography (OCTA) allows the retinal microvasculature to be visualized at various retinal depths. Previous studies introduced OCTA axial profile analysis and showed regional variations in the number and location of axially distinct vascular retinal plexuses. OCTA acquisition and processing approaches, however, vary in terms of their resulting transverse and axial resolutions, and especially the latter could potentially influence the profile analysis results. Our study imaged normal eyes using the Spectralis OCT2 with a full-spectrum, probabilistic OCTA algorithm, that, in marked contrast to split-spectrum approaches, preserves the original high OCT axial resolution also within the resulting OCTA signal. En face OCTA images are generally created by averaging flow signals over a finite axial depth window. However, we assessed regional OCTA signal profiles at each depth position at full axial resolution. All regions had two sharp vessel density peaks near the inner and outer boundaries of the inner nuclear layer, indicating separate intermediate and deep capillary plexuses. The superficial vascular plexus (SVP) separated into two distinct peaks within the ganglion cell layer in the parafoveal zone. The nasal, superior, and inferior perifovea had a deeper SVP peak that was shifted anteriorly compared to the parafoveal zone. Axial vascular density analysis with high-resolution, full spectrum OCTA thus allows healthy retinal vasculature to be precisely reconstructed and may be useful for clinically assessing retinal pathology.

Consumer preferences for mild cheddar cheese flavors.

PubMed

Drake, S L; Gerard, P D; Drake, M A

2008-11-01

Flavor is an important factor in consumer selection of cheeses. Mild Cheddar cheese is the classification used to describe Cheddar cheese that is not aged extensively and has a "mild" flavor. However, there is no legal definition or age limit for Cheddar cheese to be labeled mild, medium, or sharp, nor are the flavor profiles or flavor expectations of these cheeses specifically defined. The objectives of this study were to document the distinct flavor profiles among commercially labeled mild Cheddar cheeses, and to characterize if consumer preferences existed for specific mild Cheddar cheese flavors or flavor profiles. Flavor descriptive sensory profiles of a representative array of commercial Cheddar cheeses labeled as mild (n= 22) were determined using a trained sensory panel and an established cheese flavor sensory language. Nine representative Cheddar cheeses were selected for consumer testing. Consumers (n= 215) assessed the cheeses for overall liking and other consumer liking attributes. Internal preference mapping, cluster analysis, and discriminant analysis were conducted. Mild Cheddar cheeses were diverse in flavor with many displaying flavors typically associated with more age. Four distinct consumer clusters were identified. The key drivers of liking for mild Cheddar cheese were: color, cooked/milky, whey and brothy flavors, and sour taste. Consumers have distinct flavor and color preferences for mild Cheddar cheese. These results can help manufacturers understand consumer preferences for mild Cheddar cheese.

Rapid Analysis of Corni fructus Using Paper Spray-Mass Spectrometry.

PubMed

Guo, Yuan; Gu, Zhixin; Liu, Xuemei; Liu, Jingjing; Ma, Ming; Chen, Bo; Wang, Liping

2017-07-01

Paper spray-mass spectrometry (PS-MS) is a kind of ambient MS technique for the rapid analysis of samples. Corni fructus has been widely used in traditional Chinese compound preparations and healthy food. However, a number of counterfeits of Corni fructus, such as Crataegi fructus, Lycii fructus, and grape skin are illegally sold in crude herb markets. Therefore, the development of a rapid and high-throughput quality evaluation method is important for ensuring the effectiveness and safety of the crude materials of Corni fructus. To develop PS-MS chemical profiles and a semi-quantitative method of Corni fructus for quality assessment and control, and species distinction of Corni fructus. Both positive and negative ion PS-MS chemical profiles were constructed for species distinction. The statistical analysis of the chemical profiles was accomplished by principal component analysis (PCA). Rapid semi-quantitative analysis of loganin and morroniside in the extracts of Corni fructus were accomplished by PS-MS. The profiles of the Corni fructus and Crataegi fructus samples were clearly clustered into two categories. The limit of quantification (LOQ) in the semi-quantitative analysis was 6 μg/mL and 5.6 μg/mL for loganin and morroniside, respectively. PS-MS is a simple, rapid, and high-throughput method for the quality control and species distinction of Corni fructus. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Metabolite profiling and associated gene expression reveal two metabolic shifts during the seed-to-seedling transition in Arabidopsis thaliana.

PubMed

Silva, Anderson Tadeu; Ligterink, Wilco; Hilhorst, Henk W M

2017-11-01

Metabolic and transcriptomic correlation analysis identified two distinctive profiles involved in the metabolic preparation for seed germination and seedling establishment, respectively. Transcripts were identified that may control metabolic fluxes. The transition from a quiescent metabolic state (dry seed) to the active state of a vigorous seedling is crucial in the plant's life cycle. We analysed this complex physiological trait by measuring the changes in primary metabolism that occur during the transition in order to determine which metabolic networks are operational. The transition involves several developmental stages from seed germination to seedling establishment, i.e. between imbibition of the mature dry seed and opening of the cotyledons, the final stage of seedling establishment. We hypothesized that the advancement of growth is associated with certain signature metabolite profiles. Metabolite-metabolite correlation analysis underlined two specific profiles which appear to be involved in the metabolic preparation for seed germination and efficient seedling establishment, respectively. Metabolite profiles were also compared to transcript profiles and although transcriptional changes did not always equate to a proportional metabolic response, in depth correlation analysis identified several transcripts that may directly influence the flux through metabolic pathways during the seed-to-seedling transition. This correlation analysis also pinpointed metabolic pathways which are significant for the seed-to-seedling transition, and metabolite contents that appeared to be controlled directly by transcript abundance. This global view of the transcriptional and metabolic changes during the seed-to-seedling transition in Arabidopsis opens up new perspectives for understanding the complex regulatory mechanism underlying this transition.

Memory T cells in organ transplantation: progress and challenges

PubMed Central

Espinosa, Jaclyn R.; Samy, Kannan P.; Kirk, Allan D.

2017-01-01

Antigen-experienced T cells, also known as memory T cells, are functionally and phenotypically distinct from naive T cells. Their enhanced expression of adhesion molecules and reduced requirement for co-stimulation enables them to mount potent and rapid recall responses to subsequent antigen encounters. Memory T cells generated in response to prior antigen exposures can cross-react with other nonidentical, but similar, antigens. This heterologous cross-reactivity not only enhances protective immune responses, but also engenders de novo alloimmunity. This latter characteristic is increasingly recognized as a potential barrier to allograft acceptance that is worthy of immunotherapeutic intervention, and several approaches have been investigated. Calcineurin inhibition effectively controls memory T-cell responses to allografts, but this benefit comes at the expense of increased infectious morbidity. Lymphocyte depletion eliminates allospecific T cells but spares memory T cells to some extent, such that patients do not completely lose protective immunity. Co-stimulation blockade is associated with reduced adverse-effect profiles and improved graft function relative to calcineurin inhibition, but lacks efficacy in controlling memory T-cell responses. Targeting the adhesion molecules that are upregulated on memory T cells might offer additional means to control co-stimulation-blockade-resistant memory T-cell responses. PMID:26923209

Diversity of Staphylococcus pseudintermedius in carriage sites and skin lesions of dogs with superficial bacterial folliculitis: potential implications for diagnostic testing and therapy.

PubMed

Larsen, Rikke Friis; Boysen, Lene; Jessen, Lisbeth Rem; Guardabassi, Luca; Damborg, Peter

2018-05-21

Staphylococcus pseudintermedius is genotypically diverse within the canine population and multiple strains may colonize individual dogs at any given time. If multiple strains with distinct antimicrobial resistance profiles are present in superficial bacterial folliculitis (SBF), sampling a single skin lesion for culture and antimicrobial susceptibility testing (AST) might be inadequate to select effective therapy. To investigate S. pseudintermedius diversity in carriage sites and lesions of dogs with SBF. Fourteen dogs with SBF. Staphylococcus pseudintermedius isolates obtained from perineum, gingiva and four to six skin lesions per dog were subjected to pulsed-field gel electrophoresis (PFGE) and AST to assess diversity between lesions. For two dogs, 14-16 isolates per lesion were included in the analysis to assess diversity within lesions. Analysis of one isolate per lesion revealed one to four strains displaying unique PFGE profiles, and up to three unique antimicrobial resistance (AMR) profiles for each dog. Multiple pustules from the same dog always harboured the same strain, whereas papules, crusts and collarettes did not. Up to four strains with distinct AMR profiles were isolated from the same lesion in two dogs. In 12 dogs, at least one carriage site strain also was represented in lesions. Lesions of SBF may harbour multiple S. pseudintermedius strains with distinct antimicrobial resistance profiles. Pustules are the best target for bacterial culture. It remains unclear whether isolation of different strains from other lesion types is a consequence of contamination or co-infection by multiple strains. © 2018 ESVD and ACVD.

A Latent Profile Analysis of University Students' Self-Regulated Learning Strategies

ERIC Educational Resources Information Center

Ning, Hoi Kwan; Downing, Kevin

2015-01-01

Based on self-reported cognitive, metacognitive, and behavioural strategy measures obtained from 828 final-year students from a university in Hong Kong, latent profile analysis (LPA) identified four distinct types of students with differential self-regulated learning strategy orientations: "competent self-regulated learners",…

Antennal olfactory sensilla responses to insect chemical repellents in the common bed bug, Cimex lectularius.

PubMed

Liu, Feng; Haynes, Kenneth F; Appel, Arthur G; Liu, Nannan

2014-06-01

Populations of the common bed bug Cimex lectularius (Hemiptera; Cimicidae), a temporary ectoparasite on both humans and animals, have surged in many developed countries. Similar to other haematophagous arthropods, C. lectularius relies on its olfactory system to detect semiochemicals in the environment, including both attractants and repellents. To elucidate the olfactory responses of the common bed bug to commonly used insect chemical repellents, particularly haematophagous repellents, we investigated the neuronal responses of individual olfactory sensilla in C. lectularius' antennae to 52 insect chemical repellents, both synthetic and botanic. Different types of sensilla displayed highly distinctive response profiles. While C sensilla did not respond to any of the insect chemical repellents, Dγ sensilla proved to be the most sensitive in response to terpene-derived insect chemical repellents. Different chemical repellents elicited neuronal responses with differing temporal characteristics, and the responses of the olfactory sensilla to the insect chemical repellents were dose-dependent, with an olfactory response to the terpene-derived chemical repellent, but not to the non-terpene-derived chemical repellents. Overall, this study furnishes a comprehensive map of the olfactory response of bed bugs to commonly used insect chemical repellents, providing useful information for those developing new agents (attractants or repellents) for bed bug control.

High spatial correspondence at a columnar level between activation and resting state fMRI signals and local field potentials.

PubMed

Shi, Zhaoyue; Wu, Ruiqi; Yang, Pai-Feng; Wang, Feng; Wu, Tung-Lin; Mishra, Arabinda; Chen, Li Min; Gore, John C

2017-05-16

Although blood oxygenation level-dependent (BOLD) fMRI has been widely used to map brain responses to external stimuli and to delineate functional circuits at rest, the extent to which BOLD signals correlate spatially with underlying neuronal activity, the spatial relationships between stimulus-evoked BOLD activations and local correlations of BOLD signals in a resting state, and whether these spatial relationships vary across functionally distinct cortical areas are not known. To address these critical questions, we directly compared the spatial extents of stimulated activations and the local profiles of intervoxel resting state correlations for both high-resolution BOLD at 9.4 T and local field potentials (LFPs), using 98-channel microelectrode arrays, in functionally distinct primary somatosensory areas 3b and 1 in nonhuman primates. Anatomic images of LFP and BOLD were coregistered within 0.10 mm accuracy. We found that the point spread functions (PSFs) of BOLD and LFP responses were comparable in the stimulus condition, and both estimates of activations were slightly more spatially constrained than local correlations at rest. The magnitudes of stimulus responses in area 3b were stronger than those in area 1 and extended in a medial to lateral direction. In addition, the reproducibility and stability of stimulus-evoked activation locations within and across both modalities were robust. Our work suggests that the intrinsic resolution of BOLD is not a limiting feature in practice and approaches the intrinsic precision achievable by multielectrode electrophysiology.

Systematic pan-cancer analysis reveals immune cell interactions in the tumor microenvironment

PubMed Central

Varn, Frederick S.; Wang, Yue; Mullins, David W.; Fiering, Steven; Cheng, Chao

2017-01-01

With the recent advent of immunotherapy, there is a critical need to understand immune cell interactions in the tumor microenvironment in both pan-cancer and tissue-specific contexts. Multi-dimensional datasets have enabled systematic approaches to dissect these interactions in large numbers of patients, furthering our understanding of the patient immune response to solid tumors. Using an integrated approach, we inferred the infiltration levels of distinct immune cell subsets in 23 tumor types from The Cancer Genome Atlas. From these quantities, we constructed a co-infiltration network, revealing interactions between cytolytic cells and myeloid cells in the tumor microenvironment. By integrating patient mutation data, we found that while mutation burden was associated with immune infiltration differences between distinct tumor types, additional factors likely explained differences between tumors originating from the same tissue. We concluded this analysis by examining the prognostic value of individual immune cell subsets as well as how co-infiltration of functionally discordant cell types associated with patient survival. In multiple tumor types, we found that the protective effect of CD8+ T cell infiltration was heavily modulated by co-infiltration of macrophages and other myeloid cell types, suggesting the involvement of myeloid-derived suppressor cells in tumor development. Our findings illustrate complex interactions between different immune cell types in the tumor microenvironment and indicate these interactions play meaningful roles in patient survival. These results demonstrate the importance of personalized immune response profiles when studying the factors underlying tumor immunogenicity and immunotherapy response. PMID:28126714

High spatial correspondence at a columnar level between activation and resting state fMRI signals and local field potentials

PubMed Central

Shi, Zhaoyue; Wu, Ruiqi; Yang, Pai-Feng; Wang, Feng; Wu, Tung-Lin; Mishra, Arabinda; Chen, Li Min; Gore, John C.

2017-01-01

Although blood oxygenation level-dependent (BOLD) fMRI has been widely used to map brain responses to external stimuli and to delineate functional circuits at rest, the extent to which BOLD signals correlate spatially with underlying neuronal activity, the spatial relationships between stimulus-evoked BOLD activations and local correlations of BOLD signals in a resting state, and whether these spatial relationships vary across functionally distinct cortical areas are not known. To address these critical questions, we directly compared the spatial extents of stimulated activations and the local profiles of intervoxel resting state correlations for both high-resolution BOLD at 9.4 T and local field potentials (LFPs), using 98-channel microelectrode arrays, in functionally distinct primary somatosensory areas 3b and 1 in nonhuman primates. Anatomic images of LFP and BOLD were coregistered within 0.10 mm accuracy. We found that the point spread functions (PSFs) of BOLD and LFP responses were comparable in the stimulus condition, and both estimates of activations were slightly more spatially constrained than local correlations at rest. The magnitudes of stimulus responses in area 3b were stronger than those in area 1 and extended in a medial to lateral direction. In addition, the reproducibility and stability of stimulus-evoked activation locations within and across both modalities were robust. Our work suggests that the intrinsic resolution of BOLD is not a limiting feature in practice and approaches the intrinsic precision achievable by multielectrode electrophysiology. PMID:28461461

Complex Modulation of the Aedes aegypti Transcriptome in Response to Dengue Virus Infection

PubMed Central

Bonizzoni, Mariangela; Dunn, W. Augustine; Campbell, Corey L.; Olson, Ken E.; Marinotti, Osvaldo; James, Anthony A.

2012-01-01

Dengue fever is the most important arboviral disease world-wide, with Aedes aegypti being the major vector. Interactions between the mosquito host and dengue viruses (DENV) are complex and vector competence varies among geographically-distinct Ae. aegypti populations. Additionally, dengue is caused by four antigenically-distinct viral serotypes (DENV1–4), each with multiple genotypes. Each virus genotype interacts differently with vertebrate and invertebrate hosts. Analyses of alterations in mosquito transcriptional profiles during DENV infection are expected to provide the basis for identifying networks of genes involved in responses to viruses and contribute to the molecular-genetic understanding of vector competence. In addition, this knowledge is anticipated to support the development of novel disease-control strategies. RNA-seq technology was used to assess genome-wide changes in transcript abundance at 1, 4 and 14 days following DENV2 infection in carcasses, midguts and salivary glands of the Ae. aegypti Chetumal strain. DENV2 affected the expression of 397 Ae. aegypti genes, most of which were down-regulated by viral infection. Differential accumulation of transcripts was mainly tissue- and time-specific. Comparisons of our data with other published reports reveal conservation of functional classes, but limited concordance of specific mosquito genes responsive to DENV2 infection. These results indicate the necessity of additional studies of mosquito-DENV interactions, specifically those focused on recently-derived mosquito strains with multiple dengue virus serotypes and genotypes. PMID:23209765

Cellular Decision Making by Non-Integrative Processing of TLR Inputs.

PubMed

Kellogg, Ryan A; Tian, Chengzhe; Etzrodt, Martin; Tay, Savaş

2017-04-04

Cells receive a multitude of signals from the environment, but how they process simultaneous signaling inputs is not well understood. Response to infection, for example, involves parallel activation of multiple Toll-like receptors (TLRs) that converge on the nuclear factor κB (NF-κB) pathway. Although we increasingly understand inflammatory responses for isolated signals, it is not clear how cells process multiple signals that co-occur in physiological settings. We therefore examined a bacterial infection scenario involving co-stimulation of TLR4 and TLR2. Independent stimulation of these receptors induced distinct NF-κB dynamic profiles, although surprisingly, under co-stimulation, single cells continued to show ligand-specific dynamic responses characteristic of TLR2 or TLR4 signaling rather than a mixed response, comprising a cellular decision that we term "non-integrative" processing. Iterating modeling and microfluidic experiments revealed that non-integrative processing occurred through interaction of switch-like NF-κB activation, receptor-specific processing timescales, cell-to-cell variability, and TLR cross-tolerance mediated by multilayer negative feedback. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Tissue-enriched expression profiles in Aedes aegypti identify hemocyte-specific transcriptome responses to infection

PubMed Central

Choi, Young-Jun; Fuchs, Jeremy F.; Mayhew, George F.; Yu, Helen E.; Christensen, Bruce M.

2012-01-01

Hemocytes are integral components of mosquito immune mechanisms such as phagocytosis, melanization, and production of antimicrobial peptides. However, our understanding of hemocyte-specific molecular processes and their contribution to shaping the host immune response remains limited. To better understand the immunophysiological features distinctive of hemocytes, we conducted genome-wide analysis of hemocyte-enriched transcripts, and examined how tissue-enriched expression patterns change with the immune status of the host. Our microarray data indicate that the hemocyte-enriched trascriptome is dynamic and context-dependent. Analysis of transcripts enriched after bacterial challenge in circulating hemocytes with respect to carcass added a dimension to evaluating infection-responsive genes and immune-related gene families. We resolved patterns of transcriptional change unique to hemocytes from those that are likely shared by other immune responsive tissues, and identified clusters of genes preferentially induced in hemocytes, likely reflecting their involvement in cell type specific functions. In addition, the study revealed conserved hemocyte-enriched molecular repertoires which might be implicated in core hemocyte function by cross-species meta-analysis of microarray expression data from Anopheles gambiae and Drosophila melanogaster. PMID:22796331

Further consideration of the clonal nature of Salmonella typhi: evaluation of molecular and clinical characteristics of strains from Indonesia and Peru.

PubMed Central

Franco, A; Gonzalez, C; Levine, O S; Lagos, R; Hall, R H; Hoffman, S L; Moechtar, M A; Gotuzzo, E; Levine, M M; Hone, D M

1992-01-01

We examined envelope protein profiles, chromosomal restriction endonuclease digest patterns, and immune responses to envelope proteins for collections of Salmonella typhi strains isolated in Peru and Indonesia. Only minor differences in envelope protein patterns were apparent among strains. Strains from 7 of 20 Indonesian patients had a distinct chromosomal digest pattern compared with patterns of Peruvian and other Indonesian strains. Strains with this pattern carried the gene for the j flagellar antigen (H1-j); differences in response to envelope proteins of j and d strains were noted on immunoblot analysis. Our data suggest that there are genotypic and phenotypic differences among S. typhi strains. The clinical importance of these differences remains to be fully evaluated; however, in this study it was not possible to show a clear correlation between strain characteristics and disease severity. Images PMID:1500532

Clozapine response and plasma catecholamines and their metabolites.

PubMed

Green, A I; Alam, M Y; Sobieraj, J T; Pappalardo, K M; Waternaux, C; Salzman, C; Schatzberg, A F; Schildkraut, J J

1993-02-01

The atypical neuroleptic clozapine has an unusual profile of clinical effects and a distinctive spectrum of pharmacological actions. Plasma measures of catecholamines and their metabolites have been used in the past to study the action of typical neuroleptics. We obtained longitudinal assessments of plasma measures of dopamine (pDA), norepinephrine (pNE), and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG), in eight treatment-resistant or treatment-intolerant schizophrenic patients who were treated with clozapine for 12 weeks following a prolonged drug-washout period. Our findings from the study of these eight patients suggest the following: Plasma levels of HVA and possibly NE derived from the neuroleptic-free baseline period may predict response to clozapine; plasma levels of HVA and MHPG decrease during the initial weeks of treatment in responders but not in nonresponders; and plasma levels of DA and NE increase in both responders and nonresponders to clozapine.

The health advantage of a vegan diet: exploring the gut microbiota connection.

PubMed

Glick-Bauer, Marian; Yeh, Ming-Chin

2014-10-31

This review examines whether there is evidence that a strict vegan diet confers health advantages beyond that of a vegetarian diet or overall healthy eating. Few studies include vegan subjects as a distinct experimental group, yet when vegan diets are directly compared to vegetarian and omnivorous diets, a pattern of protective health benefits emerges. The relatively recent inclusion of vegan diets in studies of gut microbiota and health allows us the opportunity to assess whether the vegan gut microbiota is distinct, and whether the health advantages characteristic of a vegan diet may be partially explained by the associated microbiota profile. The relationship between diet and the intestinal microbial profile appears to follow a continuum, with vegans displaying a gut microbiota most distinct from that of omnivores, but not always significantly different from that of vegetarians. The vegan gut profile appears to be unique in several characteristics, including a reduced abundance of pathobionts and a greater abundance of protective species. Reduced levels of inflammation may be the key feature linking the vegan gut microbiota with protective health effects. However, it is still unclear whether a therapeutic vegan diet can be prescribed to alter the gut microflora for long-term health benefits.

The Health Advantage of a Vegan Diet: Exploring the Gut Microbiota Connection

PubMed Central

Glick-Bauer, Marian; Yeh, Ming-Chin

2014-01-01

This review examines whether there is evidence that a strict vegan diet confers health advantages beyond that of a vegetarian diet or overall healthy eating. Few studies include vegan subjects as a distinct experimental group, yet when vegan diets are directly compared to vegetarian and omnivorous diets, a pattern of protective health benefits emerges. The relatively recent inclusion of vegan diets in studies of gut microbiota and health allows us the opportunity to assess whether the vegan gut microbiota is distinct, and whether the health advantages characteristic of a vegan diet may be partially explained by the associated microbiota profile. The relationship between diet and the intestinal microbial profile appears to follow a continuum, with vegans displaying a gut microbiota most distinct from that of omnivores, but not always significantly different from that of vegetarians. The vegan gut profile appears to be unique in several characteristics, including a reduced abundance of pathobionts and a greater abundance of protective species. Reduced levels of inflammation may be the key feature linking the vegan gut microbiota with protective health effects. However, it is still unclear whether a therapeutic vegan diet can be prescribed to alter the gut microflora for long-term health benefits. PMID:25365383

Microbial genome-enabled insights into plant-microorganism interactions.

PubMed

Guttman, David S; McHardy, Alice C; Schulze-Lefert, Paul

2014-12-01

Advances in genome-based studies on plant-associated microorganisms have transformed our understanding of many plant pathogens and are beginning to greatly widen our knowledge of plant interactions with mutualistic and commensal microorganisms. Pathogenomics has revealed how pathogenic microorganisms adapt to particular hosts, subvert innate immune responses and change host range, as well as how new pathogen species emerge. Similarly, culture-independent community profiling methods, coupled with metagenomic and metatranscriptomic studies, have provided the first insights into the emerging field of research on plant-associated microbial communities. Together, these approaches have the potential to bridge the gap between plant microbial ecology and plant pathology, which have traditionally been two distinct research fields.

Comorbid obsessive-compulsive personality disorder in obsessive-compulsive disorder (OCD): a marker of severity.

PubMed

Lochner, Christine; Serebro, Paul; van der Merwe, Lize; Hemmings, Sian; Kinnear, Craig; Seedat, Soraya; Stein, Dan J

2011-06-01

Comorbid obsessive-compulsive personality disorder (OCPD) is well-described in obsessive-compulsive disorder (OCD). It remains unclear, however, whether OCPD in OCD represents a distinct subtype of OCD or whether it is simply a marker of severity in OCD. The aim of this study was to compare a large sample of OCD subjects (n=403) with and without OCPD on a range of demographic, clinical and genetic characteristics to evaluate whether comorbid OCPD in OCD represents a distinct subtype of OCD, or is a marker of severity. Our findings suggest that OCD with and without OCPD are similar in terms of gender distribution and age at onset of OC symptoms. Compared to OCD-OCPD (n=267, 66%), those with OCD+OCPD (n=136, 34%) are more likely to present with the OC symptom dimensions which reflect the diagnostic criteria for OCPD (e.g., hoarding), and have significantly greater OCD severity, comorbidity, functional impairment, and poorer insight. Furthermore there are no differences in distribution of gene variants, or response to treatment in the two groups. The majority of our findings suggest that in OCD, patients with OCPD do not have a highly distinctive phenomenological or genetic profile, but rather that OCPD represents a marker of severity. Copyright © 2011 Elsevier Inc. All rights reserved.

New daily persistent headache with a thunderclap headache onset and complete response to nimodipine (a new distinct subtype of NDPH).

PubMed

Rozen, Todd D; Beams, Jennifer L

2013-12-23

At present new daily persistent headache is just a group of conditions that are connected based on the temporal profile of their mode of onset. If new daily persistent headache is a true distinct syndrome like migraine then we need to start to define subtypes that have specific effective treatments such has been noted for migraine sub-forms. We present what we believe is the first recognized subtype of new daily persistent headache that which starts with a thunderclap headache onset. A patient presented with a 13 month history of a daily headache from onset which initiated as a thunderclap headache along with persistent acalculia. All neuroimaging studies for secondary causes were negative. Nimodipine rapidly and completely alleviated her headache and associated neurologic symptoms. We propose that this subtype of new daily persistent headache is caused by a very rapid increase in CSF tumor necrosis factor alpha levels leading to cerebral artery vasospasm with a subsequent thunderclap headache, then continuous or near continuous cerebral artery vasospasm leading to a persistent daily headache. Nimodipine which not only inhibits cerebral artery vasospasm but also tumor necrosis factor alpha production appears to be a specific treatment for this distinct subtype of new daily persistent headache.

New daily persistent headache with a thunderclap headache onset and complete response to Nimodipine (A new distinct subtype of NDPH)

PubMed Central

2013-01-01

At present new daily persistent headache is just a group of conditions that are connected based on the temporal profile of their mode of onset. If new daily persistent headache is a true distinct syndrome like migraine then we need to start to define subtypes that have specific effective treatments such has been noted for migraine sub-forms. We present what we believe is the first recognized subtype of new daily persistent headache that which starts with a thunderclap headache onset. A patient presented with a 13 month history of a daily headache from onset which initiated as a thunderclap headache along with persistent acalculia. All neuroimaging studies for secondary causes were negative. Nimodipine rapidly and completely alleviated her headache and associated neurologic symptoms. We propose that this subtype of new daily persistent headache is caused by a very rapid increase in CSF tumor necrosis factor alpha levels leading to cerebral artery vasospasm with a subsequent thunderclap headache, then continuous or near continuous cerebral artery vasospasm leading to a persistent daily headache. Nimodipine which not only inhibits cerebral artery vasospasm but also tumor necrosis factor alpha production appears to be a specific treatment for this distinct subtype of new daily persistent headache. PMID:24364890

A Comprehensive Examination of Reading Heterogeneity in Students with High Functioning Autism: Distinct Reading Profiles and Their Relation to Autism Symptom Severity

ERIC Educational Resources Information Center

McIntyre, Nancy S.; Solari, Emily J.; Grimm, Ryan P.; E. Lerro, Lindsay; E. Gonzales, Joseph; Mundy, Peter C.

2017-01-01

The goal of this study was to identify unique profiles of readers in a sample of 8-16 year olds with higher functioning autism spectrum disorders (HFASD) and examine the profiles in relation to ASD symptom severity. Eighty-one students were assessed utilizing a comprehensive reading battery that included basic word reading, language, and…

A Comprehensive Examination of Reading Heterogeneity in Students with High Functioning Autism: Distinct Reading Profiles and Their Relations to Autism Symptom Severity

ERIC Educational Resources Information Center

McIntyre, Nancy S.; Solari, Emily J.; Grimm, Ryan P.; Lerro, Lindsay E.; Gonzalez, Joseph E.; Mundy, Peter C.

2017-01-01

The goal of this study was to identify unique profiles of readers in a sample of 8-16 year olds with higher functioning autism spectrum disorders (HFASD) and examine the profiles in relation to ASD symptom severity. Eighty-one students were assessed utilizing a comprehensive reading battery that included basic word reading, language, and…

How Do Different Ways of Measuring Individual Differences in Zero-Acquaintance Personality Judgment Accuracy Correlate With Each Other?

PubMed

Hall, Judith A; Back, Mitja D; Nestler, Steffen; Frauendorfer, Denise; Schmid Mast, Marianne; Ruben, Mollie A

2018-04-01

This research compares two different approaches that are commonly used to measure accuracy of personality judgment: the trait accuracy approach wherein participants discriminate among targets on a given trait, thus making intertarget comparisons, and the profile accuracy approach wherein participants discriminate between traits for a given target, thus making intratarget comparisons. We examined correlations between these methods as well as correlations among accuracies for judging specific traits. The present article documents relations among these approaches based on meta-analysis of five studies of zero-acquaintance impressions of the Big Five traits. Trait accuracies correlated only weakly with overall and normative profile accuracy. Substantial convergence between the trait and profile accuracy methods was only found when an aggregate of all five trait accuracies was correlated with distinctive profile accuracy. Importantly, however, correlations between the trait and profile accuracy approaches were reduced to negligibility when statistical overlap was corrected by removing the respective trait from the profile correlations. Moreover, correlations of the separate trait accuracies with each other were very weak. Different ways of measuring individual differences in personality judgment accuracy are not conceptually and empirically the same, but rather represent distinct abilities that rely on different judgment processes. © 2017 Wiley Periodicals, Inc.

Latent profiles of problem behavior within learning, peer, and teacher contexts: identifying subgroups of children at academic risk across the preschool year.

PubMed

Bulotsky-Shearer, Rebecca J; Bell, Elizabeth R; Domínguez, Ximena

2012-12-01

Employing a developmental and ecological model, the study identified initial levels and rates of change in academic skills for subgroups of preschool children exhibiting problem behavior within routine classroom situations. Six distinct latent profile types of emotional and behavioral adjustment were identified for a cohort of low-income children early in the preschool year (N=4417). Profile types provided a descriptive picture of patterns of classroom externalizing, internalizing, and situational adjustment problems common to subgroups of children early in the preschool year. The largest profile type included children who exhibited low problem behavior and were characterized as well-adjusted to the preschool classroom early in the year. The other profile types were characterized by distinct combinations of elevated internalizing, externalizing, and situational problem behavior. Multinomial logistic regression identified younger children and boys at increased risk for classification in problem types, relative to the well-adjusted type. Latent growth models indicated that children classified within the extremely socially and academically disengaged profile type, started and ended the year with the lowest academic skills, relative to all other types. Implications for future research, policy, and practice are discussed. Copyright © 2012 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Aerodynamic profiles of women with muscle tension dysphonia/aphonia.

PubMed

Gillespie, Amanda I; Gartner-Schmidt, Jackie; Rubinstein, Elaine N; Abbott, Katherine Verdolini

2013-04-01

In this study, the authors aimed to (a) determine whether phonatory airflows and estimated subglottal pressures (est-Psub) for women with primary muscle tension dysphonia/aphonia (MTD/A) differ from those for healthy speakers; (b) identify different aerodynamic profile patterns within the MTD/A subject group; and (c) determine whether results suggest new understanding of pathogenesis in MTD/A. Retrospective review of aerodynamic data collected from 90 women at the time of primary MTD/A diagnosis. Aerodynamic profiles were significantly different for women with MTD/A as compared with healthy speakers. Five distinct profiles were identified: (a) normal flow, normal est-Psub; (b) high flow, high est-Psub; (c) low flow, normal est-Psub; (d) normal flow, high est-Psub; and (e) high flow, normal est-Psub. This study is the first to identify distinct subgroups of aerodynamic profiles in women with MTD/A and to quantitatively identify a clinical phenomenon sometimes described in association with it-"breath holding"-that is shown by low airflow with normal est-Psub. Results were consistent with clinical claims that diverse respiratory and laryngeal functions may underlie phonatory patterns associated with MTD/A. One potential mechanism, based in psychobiological theory, is introduced to explain some of the variability in aerodynamic profiles of women with MTD/A.

Dyadic Power Profiles: Power-Contingent Strategies for Value Creation in Negotiation

ERIC Educational Resources Information Center

Olekalns, Mara; Smith, Philip Leigh

2013-01-01

Using a simulated employment negotiation, we tested the conditional relationships among dyadic power profiles (symmetric high, symmetric low, and asymmetric), the choice and sequencing of strategies, and value creation. We showed that negotiators in symmetric high, symmetric low, and asymmetric power dyads took distinctly different paths to value…

An Examination of Learning Profiles in Physical Education

ERIC Educational Resources Information Center

Shen, Bo; Chen, Ang

2007-01-01

Using the model of domain learning as a theoretical framework, the study was designed to examine the extent to which learners' initial learning profiles based on previously acquired knowledge, learning strategy application, and interest-based motivation were distinctive in learning softball. Participants were 177 sixth-graders from three middle…

Profiling Learners' Achievement Goals when Completing Academic Essays

ERIC Educational Resources Information Center

Ng, Chi-Hung Clarence

2009-01-01

This study explored adult learners' goal profiles in relation to the completion of a compulsory academic essay. Based on learners' scores on items assessing mastery, performance-approach, and work-avoidance goals, cluster analyses produced three distinct categories of learners: performance-focused, work-avoidant, and multiple-goal learners. These…

Plasma Acylcarnitine Profiles Suggest Incomplete Fatty Acid ß-Oxidation and Altered Tricarboxylic Cycle Activity in Type 2 Diabetic African-American Women

USDA-ARS?s Scientific Manuscript database

Inefficient muscle long-chain fatty acid (LCFA) combustion is associated with insulin resistance, but molecular links between mitochondrial fat catabolism and insulin action remain controversial. We hypothesized that plasma acylcarnitine profiling would identify distinct metabolite patterns reflect...

Treatment Service Patterns and Organizational Structures: An Analysis of Programs in DATOS-A.

ERIC Educational Resources Information Center

Delany, Peter J.; Broome, Kirk M.; Flynn, Patrick M.; Fletcher, Bennett W.

2001-01-01

Examined availability of various treatment services within a national sample of programs treating adolescent drug abuse patients. Created treatment service delivery profiles and examined them in context of organizational variables. Found that distinct profiles of services existed within residential and outpatient modalities and that these service…

Mostly Heterosexual as a Distinct Sexual Orientation Group: A Systematic Review of the Empirical Evidence

ERIC Educational Resources Information Center

Savin-Williams, Ritch C.; Vrangalova, Zhana

2013-01-01

We reviewed empirical evidence regarding whether mostly heterosexual exists as a sexual orientation distinct from two adjacent groups on a sexual continuum--exclusively heterosexual and substantially bisexual. We addressed the question: Do mostly heterosexuals show a unique profile of sexual and romantic characteristics that distinguishes them as…

Profiling of wheat class III peroxidase genes derived from powdery mildew-attacked epidermis reveals distinct sequence-associated expression patterns.

PubMed

Liu, Guosheng; Sheng, Xiaoyan; Greenshields, David L; Ogieglo, Adam; Kaminskyj, Susan; Selvaraj, Gopalan; Wei, Yangdou

2005-07-01

A cDNA library was constructed from leaf epidermis of diploid wheat (Triticum monococcum) infected with the powdery mildew fungus (Blumeria graminis f. sp. tritici) and was screened for genes encoding peroxidases. From 2,500 expressed sequence tags (ESTs), 36 cDNAs representing 10 peroxidase genes (designated TmPRX1 to TmPRX10) were isolated and further characterized. Alignment of the deduced amino acid sequences and phylogenetic clustering with peroxidases from other plant species demonstrated that these peroxidases fall into four distinct groups. Differential expression and tissue-specific localization among the members were observed during the B. graminis f. sp. tritici attack using Northern blots and reverse-transcriptase polymerase chain reaction analyses. Consistent with its abundance in the EST collection, TmPRX1 expression showed the highest induction during pathogen attack and fluctuated in response to the fungal parasitic stages. TmPRX1 to TmPRX6 were expressed predominantly in mesophyll cells, whereas TmPRX7 to TmPRX10, which feature a putative C-terminal propeptide, were detectable mainly in epidermal cells. Using TmPRX8 as a representative, we demonstrated that its C-terminal propeptide was sufficient to target a green fluorescent protein fusion protein to the vacuoles in onion cells. Finally, differential expression profiles of the TmPRXs after abiotic stresses and signal molecule treatments were used to dissect the potential role of these peroxidases in multiple stress and defense pathways.

Climate change and physical disturbance manipulations result in distinct biological soil crust communities.

PubMed

Steven, Blaire; Kuske, Cheryl R; Gallegos-Graves, La Verne; Reed, Sasha C; Belnap, Jayne

2015-11-01

Biological soil crusts (biocrusts) colonize plant interspaces in many drylands and are critical to soil nutrient cycling. Multiple climate change and land use factors have been shown to detrimentally impact biocrusts on a macroscopic (i.e., visual) scale. However, the impact of these perturbations on the bacterial components of the biocrusts remains poorly understood. We employed multiple long-term field experiments to assess the impacts of chronic physical (foot trampling) and climatic changes (2°C soil warming, altered summer precipitation [wetting], and combined warming and wetting) on biocrust bacterial biomass, composition, and metabolic profile. The biocrust bacterial communities adopted distinct states based on the mechanism of disturbance. Chronic trampling decreased biomass and caused small community compositional changes. Soil warming had little effect on biocrust biomass or composition, while wetting resulted in an increase in the cyanobacterial biomass and altered bacterial composition. Warming combined with wetting dramatically altered bacterial composition and decreased Cyanobacteria abundance. Shotgun metagenomic sequencing identified four functional gene categories that differed in relative abundance among the manipulations, suggesting that climate and land use changes affected soil bacterial functional potential. This study illustrates that different types of biocrust disturbance damage biocrusts in macroscopically similar ways, but they differentially impact the resident soil bacterial communities, and the communities' functional profiles can differ depending on the disturbance type. Therefore, the nature of the perturbation and the microbial response are important considerations for management and restoration of drylands. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Climate change and physical disturbance manipulations result in distinct biological soil crust communities

USGS Publications Warehouse

Steven, Blaire; Kuske, Cheryl R.; Gallegos-Graves, La Verne; Reed, Sasha C.; Belnap, Jayne

2015-01-01

Biological soil crusts (biocrusts) colonize plant interspaces in many drylands and are critical to soil nutrient cycling. Multiple climate change and land use factors have been shown to detrimentally impact biocrusts on a macroscopic (i.e., visual) scale. However, the impact of these perturbations on the bacterial components of the biocrusts remain poorly understood. We employed multiple long-term field experiments to assess the impacts of chronic physical (foot trampling) and climatic changes (2 °C soil warming, altered summer precipitation (wetting), and combined warming and wetting) on biocrust bacterial biomass, composition, and metabolic profile. The biocrust bacterial communities adopted distinct states based on the mechanism of disturbance. Chronic trampling decreased biomass and caused small community compositional change. Soil warming had little effect on biocrust biomass or composition, while wetting resulted in an increase in cyanobacterial biomass and altered bacterial composition. Warming combined with wetting dramatically altered bacterial composition and decreased cyanobacteria abundance. Shotgun metagenomic sequencing identified four functional gene categories that differed in relative abundance among the manipulations, suggesting that climate and land use changes affected soil bacterial functional potential. This study illustrates that different types of biocrust disturbance damage biocrusts in macroscopically similar ways, but they differentially impact the resident soil bacterial communities and the community functional profile can differ depending on the disturbance type. Therefore, the nature of the perturbation and the microbial response are important considerations for management and restoration of drylands.

Understanding the mechanisms of radiation belt dropouts observed by Van Allen Probes

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

Xiang, Zheng; Tu, Weichao; Li, Xinlin

To achieve a better understanding of the dominant loss mechanisms for the rapid dropouts of radiation belt electrons, three distinct radiation belt dropout events observed by Van Allen Probes are comprehensively investigated. For each event, observations of the pitch angle distribution of electron fluxes and electromagnetic ion cyclotron (EMIC) waves are analyzed to determine the effects of atmospheric precipitation loss due to pitch angle scattering induced by EMIC waves. Last closed drift shells (LCDS) and magnetopause standoff position are obtained to evaluate the effects of magnetopause shadowing loss. Evolution of electron phase space density (PSD) versus L* profiles and themore » μ and K (first and second adiabatic invariants) dependence of the electron PSD drops are calculated to further analyze the dominant loss mechanisms at different L*. Here, our findings suggest that these radiation belt dropouts can be classified into distinct classes in terms of dominant loss mechanisms: magnetopause shadowing dominant, EMIC wave scattering dominant, and combination of both mechanisms. Different from previous understanding, our results show that magnetopause shadowing can deplete electrons at L* < 4, while EMIC waves can efficiently scatter electrons at L* > 4. Compared to the magnetopause standoff position, it is more reliable to use LCDS to evaluate the impact of magnetopause shadowing. Finally, the evolution of electron PSD versus L* profile and the μ, K dependence of electron PSD drops can provide critical and credible clues regarding the mechanisms responsible for electron losses at different L* over the outer radiation belt.« less

Understanding the Mechanisms of Radiation Belt Dropouts Observed by Van Allen Probes

NASA Astrophysics Data System (ADS)

Xiang, Zheng; Tu, Weichao; Li, Xinlin; Ni, Binbin; Morley, S. K.; Baker, D. N.

2017-10-01

To achieve a better understanding of the dominant loss mechanisms for the rapid dropouts of radiation belt electrons, three distinct radiation belt dropout events observed by Van Allen Probes are comprehensively investigated. For each event, observations of the pitch angle distribution of electron fluxes and electromagnetic ion cyclotron (EMIC) waves are analyzed to determine the effects of atmospheric precipitation loss due to pitch angle scattering induced by EMIC waves. Last closed drift shells (LCDS) and magnetopause standoff position are obtained to evaluate the effects of magnetopause shadowing loss. Evolution of electron phase space density (PSD) versus L* profiles and the μ and K (first and second adiabatic invariants) dependence of the electron PSD drops are calculated to further analyze the dominant loss mechanisms at different L*. Our findings suggest that these radiation belt dropouts can be classified into distinct classes in terms of dominant loss mechanisms: magnetopause shadowing dominant, EMIC wave scattering dominant, and combination of both mechanisms. Different from previous understanding, our results show that magnetopause shadowing can deplete electrons at L* < 4, while EMIC waves can efficiently scatter electrons at L* > 4. Compared to the magnetopause standoff position, it is more reliable to use LCDS to evaluate the impact of magnetopause shadowing. The evolution of electron PSD versus L* profile and the μ, K dependence of electron PSD drops can provide critical and credible clues regarding the mechanisms responsible for electron losses at different L* over the outer radiation belt.

Understanding the mechanisms of radiation belt dropouts observed by Van Allen Probes

DOE PAGES

Xiang, Zheng; Tu, Weichao; Li, Xinlin; ...

2017-08-30

To achieve a better understanding of the dominant loss mechanisms for the rapid dropouts of radiation belt electrons, three distinct radiation belt dropout events observed by Van Allen Probes are comprehensively investigated. For each event, observations of the pitch angle distribution of electron fluxes and electromagnetic ion cyclotron (EMIC) waves are analyzed to determine the effects of atmospheric precipitation loss due to pitch angle scattering induced by EMIC waves. Last closed drift shells (LCDS) and magnetopause standoff position are obtained to evaluate the effects of magnetopause shadowing loss. Evolution of electron phase space density (PSD) versus L* profiles and themore » μ and K (first and second adiabatic invariants) dependence of the electron PSD drops are calculated to further analyze the dominant loss mechanisms at different L*. Here, our findings suggest that these radiation belt dropouts can be classified into distinct classes in terms of dominant loss mechanisms: magnetopause shadowing dominant, EMIC wave scattering dominant, and combination of both mechanisms. Different from previous understanding, our results show that magnetopause shadowing can deplete electrons at L* < 4, while EMIC waves can efficiently scatter electrons at L* > 4. Compared to the magnetopause standoff position, it is more reliable to use LCDS to evaluate the impact of magnetopause shadowing. Finally, the evolution of electron PSD versus L* profile and the μ, K dependence of electron PSD drops can provide critical and credible clues regarding the mechanisms responsible for electron losses at different L* over the outer radiation belt.« less

Distinct lipid/lipoprotein profiles and hormonal responsiveness in nine ethnic groups of postmenopausal Asian women: the Pan-Asia Menopause (PAM) study.

PubMed

Taechakraichana, N; Holinka, C F; Haines, C J; Subramaniam, R; Tian, X W; Ausmanas, M K

2007-06-01

Lipid/lipoprotein profiles, among other factors, are associated with risk of cardiovascular disease. Because cardiovascular disease varies in Asian countries, we hypothesized that lipid profiles differ in ethnic groups of postmenopausal Asian women. To add to the limited body of information currently available, we also investigated the effects of estrogen/progestin therapy on lipid/lipoprotein profiles in postmenopausal Asian women. The Pan-Asia Menopause (PAM) study was a prospective, randomized, double-blind clinical trial evaluating 1028 postmenopausal women at 22 investigational centers in 11 Asian countries/territories. Subjects were randomly assigned to one of three doses of continuous combined conjugated estrogens (CE)/medroxyprogesterone acetate (MPA): CE/MPA (in mg/day) = 0.625/2.5, 0.45/1.5 or 0.3/1.5. The treatment period, following baseline evaluations, consisted of six continuous 28-day cycles. Analysis of lipid profiles was a secondary objective of the PAM study. Total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), very low density cholesterol (VLDC-C), triglycerides and lipoprotein(a) were analyzed at a central laboratory by state-of-the-art methods. Mean concentrations of total cholesterol, LDL-C, VLDL-C and triglycerides differed significantly among the nine ethnic groups of postmenopausal women. This difference was independent of body mass index and age, two factors that also influenced lipid/lipoprotein profiles. Mean HDL-C concentrations also differed, but this difference was influenced by body mass index in a weak interaction. All three doses of CE/MPA significantly lowered total cholesterol. Treatment with the high and middle doses significantly lowered LDL-C, and increased HDL-C, VLDL-C and triglycerides. The high dose produced a significant decrease in lipoprotein(a). The different lipid/lipoprotein profiles in the nine ethnic groups of postmenopausal Asian women evaluated here suggest a relationship to differences in the prevalence of cardiovascular disease reported for different regions in Asia. However, the reported prevalence data on cardiovascular disease morbidity and mortality in the regions corresponding to the nine ethnic groups are insufficient to allow qualitative comparisons with the lipid profiles shown in our study. The lipid/lipoprotein changes in response to estrogen/progestin therapy observed here are consistent with those reported for Western women.

FUNCTIONAL SUBCLONE PROFILING FOR PREDICTION OF TREATMENT-INDUCED INTRA-TUMOR POPULATION SHIFTS AND DISCOVERY OF RATIONAL DRUG COMBINATIONS IN HUMAN GLIOBLASTOMA

PubMed Central

Reinartz, Roman; Wang, Shanshan; Kebir, Sied; Silver, Daniel J.; Wieland, Anja; Zheng, Tong; Küpper, Marius; Rauschenbach, Laurèl; Fimmers, Rolf; Shepherd, Timothy M.; Trageser, Daniel; Till, Andreas; Schäfer, Niklas; Glas, Martin; Hillmer, Axel M.; Cichon, Sven; Smith, Amy A.; Pietsch, Torsten; Liu, Ying; Reynolds, Brent A.; Yachnis, Anthony; Pincus, David W.; Simon, Matthias; Brüstle, Oliver; Steindler, Dennis A.; Scheffler, Björn

2016-01-01

Purpose Investigation of clonal heterogeneity may be key to understanding mechanisms of therapeutic failure in human cancer. However, little is known on the consequences of therapeutic intervention on the clonal composition of solid tumors. Experimental Design Here, we used 33 single cell-derived subclones generated from five clinical glioblastoma specimens for exploring intra- and inter-individual spectra of drug resistance profiles in vitro. In a personalized setting, we explored whether differences in pharmacological sensitivity among subclones could be employed to predict drug-dependent changes to the clonal composition of tumors. Results Subclones from individual tumors exhibited a remarkable heterogeneity of drug resistance to a library of potential anti-glioblastoma compounds. A more comprehensive intra-tumoral analysis revealed that stable genetic and phenotypic characteristics of co-existing subclones could be correlated with distinct drug sensitivity profiles. The data obtained from differential drug response analysis could be employed to predict clonal population shifts within the naïve parental tumor in vitro and in orthotopic xenografts. Furthermore, the value of pharmacological profiles could be shown for establishing rational strategies for individualized secondary lines of treatment. Conclusions Our data provide a previously unrecognized strategy for revealing functional consequences of intra-tumor heterogeneity by enabling predictive modeling of treatment-related subclone dynamics in human glioblastoma. PMID:27521447

Effects of international football matches on ambulance call profiles and volumes during the 2006 World Cup.

PubMed

Deakin, Charles D; Thompson, Fizz; Gibson, Caroline; Green, Mark

2007-06-01

Prompt ambulance attendance is aimed at improving patient care. With finite resources struggling to meet performance targets, unforeseen demand precludes the ability to tailor resources to cope with increased call volumes, and can have a marked detrimental effect on performance and hence patient care. The effects of the 2006 World Cup football matches on call volumes and profiles were analysed to understand how public events can influence demands on the ambulance service. All emergency calls to the Hampshire Ambulance Service NHS Trust (currently the Hampshire Division of South Central Ambulance Service, Winchester, UK) during the first weekend of the 2006 World Cup football matches were analysed by call volume and classification of call (call type). On the day of the first football match, call volume was over 50% higher than that on a typical Saturday, with distinct peaks before and after the inaugural match. Call profile analysis showed increases in alcohol-related emergencies, including collapse, unconsciousness, assault and road traffic accidents. The increase in assaults was particularly marked at the end of each match and increased again into the late evening. A detailed mapping of call volumes and profiles during the World Cup football shows a significant increase in overall emergency calls, mostly alcohol related. Mapping of limited resources to these patterns will allow improved responses to emergency calls.

Effects of international football matches on ambulance call profiles and volumes during the 2006 World Cup

PubMed Central

Deakin, Charles D; Thompson, Fizz; Gibson, Caroline; Green, Mark

2007-01-01

Background Prompt ambulance attendance is aimed at improving patient care. With finite resources struggling to meet performance targets, unforeseen demand precludes the ability to tailor resources to cope with increased call volumes, and can have a marked detrimental effect on performance and hence patient care. The effects of the 2006 World Cup football matches on call volumes and profiles were analysed to understand how public events can influence demands on the ambulance service. Methods All emergency calls to the Hampshire Ambulance Service NHS Trust (currently the Hampshire Division of South Central Ambulance Service, Winchester, UK) during the first weekend of the 2006 World Cup football matches were analysed by call volume and classification of call (call type). Results On the day of the first football match, call volume was over 50% higher than that on a typical Saturday, with distinct peaks before and after the inaugural match. Call profile analysis showed increases in alcohol‐related emergencies, including collapse, unconsciousness, assault and road traffic accidents. The increase in assaults was particularly marked at the end of each match and increased again into the late evening. Conclusion A detailed mapping of call volumes and profiles during the World Cup football shows a significant increase in overall emergency calls, mostly alcohol related. Mapping of limited resources to these patterns will allow improved responses to emergency calls. PMID:17513536

Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures

PubMed Central

Fernandes, Maria Cecilia; Dillon, Laura A. L.; Belew, Ashton Trey; Bravo, Hector Corrada; Mosser, David M.

2016-01-01

ABSTRACT Macrophages are mononuclear phagocytes that constitute a first line of defense against pathogens. While lethal to many microbes, they are the primary host cells of Leishmania spp. parasites, the obligate intracellular pathogens that cause leishmaniasis. We conducted transcriptomic profiling of two Leishmania species and the human macrophage over the course of intracellular infection by using high-throughput RNA sequencing to characterize the global gene expression changes and reprogramming events that underlie the interactions between the pathogen and its host. A systematic exclusion of the generic effects of large-particle phagocytosis revealed a vigorous, parasite-specific response of the human macrophage early in the infection that was greatly tempered at later time points. An analogous temporal expression pattern was observed with the parasite, suggesting that much of the reprogramming that occurs as parasites transform into intracellular forms generally stabilizes shortly after entry. Following that, the parasite establishes an intracellular niche within macrophages, with minimal communication between the parasite and the host cell later during the infection. No significant difference was observed between parasite species transcriptomes or in the transcriptional response of macrophages infected with each species. Our comparative analysis of gene expression changes that occur as mouse and human macrophages are infected by Leishmania spp. points toward a general signature of the Leishmania-macrophage infectome. PMID:27165796

Capturing the metabolomic diversity of KRAS mutants in non-small-cell lung cancer cells

PubMed Central

Marabese, Mirko; Broggini, Massimo; Pastorelli, Roberta

2014-01-01

In non-small-cell lung cancer (NSCLC), one-fifth of patients have KRAS mutations, which are considered a negative predictive factor to first-line therapy. Evidence is emerging that not all KRAS mutations have the same biological activities and possible remodeling of cell metabolism by KRAS activation might complicate the scenario. An open question is whether different KRAS mutations at codon-12 affect cellular metabolism differently with possible implications for different responses to cancer treatments. We applied an explorative mass spectrometry-based untargeted metabolomics strategy to characterize the largest possible number of metabolites that might distinguish isogenic NSCLC cells overexpressing mutated forms of KRAS at codon-12 (G12C, G12D, G12V) and the wild-type. The glutamine deprivation assay and real-time PCR were used to confirm the involvement of some of the metabolic pathways highlighted. Cell clones indicated distinct metabolomic profiles in KRAS wild-type and mutants. Clones harboring different KRAS mutations at codon-12 also had different metabolic remodeling, such as a different redox buffering system and different glutamine-dependency not driven by the transcriptional state of enzymes involved in glutaminolysis. These findings indicate that KRAS mutations at codon-12 are associated with different metabolomic profiles that might affect the responses to cancer treatments. PMID:24952473

Sucrose lyophiles: a semi-quantitative study of residual water content by total X-ray diffraction analysis.

PubMed

Bates, S; Jonaitis, D; Nail, S

2013-10-01

Total X-ray Powder Diffraction Analysis (TXRPD) using transmission geometry was able to observe significant variance in measured powder patterns for sucrose lyophilizates with differing residual water contents. Integrated diffraction intensity corresponding to the observed variances was found to be linearly correlated to residual water content as measured by an independent technique. The observed variance was concentrated in two distinct regions of the lyophilizate powder pattern, corresponding to the characteristic sucrose matrix double halo and the high angle diffuse region normally associated with free-water. Full pattern fitting of the lyophilizate powder patterns suggested that the high angle variance was better described by the characteristic diffraction profile of a concentrated sucrose/water system rather than by the free-water diffraction profile. This suggests that the residual water in the sucrose lyophilizates is intimately mixed at the molecular level with sucrose molecules forming a liquid/solid solution. The bound nature of the residual water and its impact on the sucrose matrix gives an enhanced diffraction response between 3.0 and 3.5 beyond that expected for free-water. The enhanced diffraction response allows semi-quantitative analysis of residual water contents within the studied sucrose lyophilizates to levels below 1% by weight. Copyright © 2013 Elsevier B.V. All rights reserved.

Temperature dependent evolution of wrinkled single-crystal silicon ribbons on shape memory polymers.

PubMed

Wang, Yu; Yu, Kai; Qi, H Jerry; Xiao, Jianliang

2017-10-25

Shape memory polymers (SMPs) can remember two or more distinct shapes, and thus can have a lot of potential applications. This paper presents combined experimental and theoretical studies on the wrinkling of single-crystal Si ribbons on SMPs and the temperature dependent evolution. Using the shape memory effect of heat responsive SMPs, this study provides a method to build wavy forms of single-crystal silicon thin films on top of SMP substrates. Silicon ribbons obtained from a Si-on-insulator (SOI) wafer are released and transferred onto the surface of programmed SMPs. Then such bilayer systems are recovered at different temperatures, yielding well-defined, wavy profiles of Si ribbons. The wavy profiles are shown to evolve with time, and the evolution behavior strongly depends on the recovery temperature. At relatively low recovery temperatures, both wrinkle wavelength and amplitude increase with time as evolution progresses. Finite element analysis (FEA) accounting for the thermomechanical behavior of SMPs is conducted to study the wrinkling of Si ribbons on SMPs, which shows good agreement with experiment. Merging of wrinkles is observed in FEA, which could explain the increase of wrinkle wavelength observed in the experiment. This study can have important implications for smart stretchable electronics, wrinkling mechanics, stimuli-responsive surface engineering, and advanced manufacturing.

Antioxidant Systems from Pepper (Capsicum annuum L.): Involvement in the Response to Temperature Changes in Ripe Fruits

PubMed Central

Mateos, Rosa M.; Jiménez, Ana; Román, Paloma; Romojaro, Félix; Bacarizo, Sierra; Leterrier, Marina; Gómez, Manuel; Sevilla, Francisca; del Río, Luis A.; Corpas, Francisco J.; Palma, José M.

2013-01-01

Sweet pepper is susceptible to changes in the environmental conditions, especially temperatures below 15 °C. In this work, two sets of pepper fruits (Capsicum annuum L.) which underwent distinct temperature profiles in planta were investigated. Accordingly, two harvesting times corresponding to each set were established: Harvest 1, whose fruits developed and ripened at 14.9 °C as average temperature; and Harvest 2, with average temperature of 12.4 °C. The oxidative metabolism was analyzed in all fruits. Although total ascorbate content did not vary between Harvests, a shift from the reduced to the oxidized form (dehydroascorbate), accompanied by a higher ascorbate peroxidase activity, was observed in Harvest 2 with respect to Harvest 1. Moreover, a decrease of the ascorbate-generating enzymatic system, the γ-galactono-lactone dehydrogenase, was found at Harvest 2. The activity values of the NADP-dependent dehydrogenases analyzed seem to indicate that a lower NADPH synthesis may occur in fruits which underwent lower temperature conditions. In spite of the important changes observed in the oxidative metabolism in fruits subjected to lower temperature, no oxidative stress appears to occur, as indicated by the lipid peroxidation and protein oxidation profiles. Thus, the antioxidative systems of pepper fruits seem to be involved in the response against temperature changes. PMID:23644886

Identification of characteristic aroma compounds in raw and thermally processed African giant snail (Achatina fulica).

PubMed

Lasekan, Ola; Muniady, Megala; Lin, Mee; Dabaj, Fatma

2018-04-24

Food flavor appreciation is one of the first signals along with food appearance and texture encountered by consumers during eating of food. Also, it is well known that flavor can strongly influence consumer's acceptability judgment. The increase in the consumption of snail meat across the world calls for the need to research into the aroma compounds responsible for the distinctive aroma notes of processed snail meat. The odorants responsible for the unique aroma notes in thermally processed giant African snail meats were evaluated by means of aroma extract dilution analysis (AEDA), gas chromatography-olfactometry (GC-O) and odor activity values (OAVs) respectively. Results revealed significant differences in the aroma profiles of the raw and thermally processed snail meats. Whilst the aroma profile of the raw snail meat was dominated with the floral-like β-ionone and β-iso-methyl ionone, sweaty/cheesy-like butanoic acid, and the mushroom-like 1-octen-3-one, the boiled and fried samples were dominated with the thermally generated odorants like 2-methylpyrazine, 2,5-dimethylpyrazine, 2-acetylthiazole and 2-acetylpyridine. Finally, results have shown that sotolon, 2-acetyl-1-pyrroline, 2-furanmethanethiol, 2-methylbutanal, 1-octen-3-one, octanal, furanone, 2-methoxyphenol, 2-acetylpyridine, 2-acetylthiazole, and 2-methylpyrazine contributed to the overall aroma of the thermally processed snail meat.

Expression profiling of ascorbic acid-related genes during tomato fruit development and ripening and in response to stress conditions.

PubMed

Ioannidi, Eugenia; Kalamaki, Mary S; Engineer, Cawas; Pateraki, Irene; Alexandrou, Dimitris; Mellidou, Ifigeneia; Giovannonni, James; Kanellis, Angelos K

2009-01-01

L-ascorbate (the reduced form of vitamin C) participates in diverse biological processes including pathogen defence mechanisms, and the modulation of plant growth and morphology, and also acts as an enzyme cofactor and redox status indicator. One of its chief biological functions is as an antioxidant. L-ascorbate intake has been implicated in the prevention/alleviation of varied human ailments and diseases including cancer. To study the regulation of accumulation of this important nutraceutical in fruit, the expression of 24 tomato (Solanum lycopersicon) genes involved in the biosynthesis, oxidation, and recycling of L-ascorbate during the development and ripening of fruit have been characterized. Taken together with L-ascorbate abundance data, the results show distinct changes in the expression profiles for these genes, implicating them in nodal regulatory roles during the process of L-ascorbate accumulation in tomato fruit. The expression of these genes was further studied in the context of abiotic and post-harvest stress, including the effects of heat, cold, wounding, oxygen supply, and ethylene. Important aspects of the hypoxic and post-anoxic response in tomato fruit are discussed. The data suggest that L-galactose-1-phosphate phosphatase could play an important role in regulating ascorbic acid accumulation during tomato fruit development and ripening.

Global absenteeism and presenteeism in mental health patients referred through primary care.

PubMed

Bailey, S Kathleen; Haggarty, John; Kelly, Sara

2015-01-01

Disability from mental health (MH) symptoms impairs workers' functioning. Most of what is known about the MH of workers relates to their experiences after intervention or work absence. To profile the clinical symptoms, self-reported absenteeism and presenteeism and treatment response of workers with MH symptoms at the point of accessing MH care and compare the characteristics of patients referred with or without problems related to work. Analysis of 11 years of patient data collected in a Shared Mental Health Care (SMHC) clinic referred within a primary care setting in Ontario, Canada. Multiple regression with MH disorders was used to predict absenteeism and presenteeism. Absenteeism and presenteeism were assessed using the 12-item self-administered version of the WHO-DAS 2. Symptom profiles were assessed with the Patient Health Questionnaire (PHQ). Some psychiatric disorders (depression, somatization, anxiety) contributed more to predicting absenteeism and presenteeism than others. Patients referred with work-related problems differed from the general SMHC population in terms of sex and type and number of symptoms. Treatment response was good in both groups after a mean of three treatment visits. Patients with work-related mental health complaints formed a distinct clinical group that benefitted equally from the intervention(s) provided by SMHC.

Multidimensional analysis of the frequencies and rates of cytokine secretion from single cells by quantitative microengraving.

PubMed

Han, Qing; Bradshaw, Elizabeth M; Nilsson, Björn; Hafler, David A; Love, J Christopher

2010-06-07

The large diversity of cells that comprise the human immune system requires methods that can resolve the individual contributions of specific subsets to an immunological response. Microengraving is process that uses a dense, elastomeric array of microwells to generate microarrays of proteins secreted from large numbers of individual live cells (approximately 10(4)-10(5) cells/assay). In this paper, we describe an approach based on this technology to quantify the rates of secretion from single immune cells. Numerical simulations of the microengraving process indicated an operating regime between 30 min-4 h that permits quantitative analysis of the rates of secretion. Through experimental validation, we demonstrate that microengraving can provide quantitative measurements of both the frequencies and the distribution in rates of secretion for up to four cytokines simultaneously released from individual viable primary immune cells. The experimental limits of detection ranged from 0.5 to 4 molecules/s for IL-6, IL-17, IFNgamma, IL-2, and TNFalpha. These multidimensional measures resolve the number and intensities of responses by cells exposed to stimuli with greater sensitivity than single-parameter assays for cytokine release. We show that cells from different donors exhibit distinct responses based on both the frequency and magnitude of cytokine secretion when stimulated under different activating conditions. Primary T cells with specific profiles of secretion can also be recovered after microengraving for subsequent expansion in vitro. These examples demonstrate the utility of quantitative, multidimensional profiles of single cells for analyzing the diversity and dynamics of immune responses in vitro and for identifying rare cells from clinical samples.

The Cortisol Awakening Response Mediates the Relationship Between Acculturative Stress and Self-Reported Health in Mexican Americans.

PubMed

Garcia, Antonio F; Wilborn, Kristin; Mangold, Deborah L

2017-12-01

The assessment of acculturative stress as synonymous with acculturation level overlooks the dynamic, interactive, and developmental nature of the acculturation process. An individual's unique perception and response to a range of stressors at each stage of the dynamic process of acculturation may be associated with stress-induced alterations in important biological response systems that mediate health outcomes. Evidence suggests the cortisol awakening response (CAR) is a promising pre-clinical biomarker of stress exposure that may link acculturative stress to self-reported health in Mexican Americans. The aim of the current study was to examine whether alterations in the CAR mediate the relationship between acculturative stress and self-reported health in Mexican Americans. Salivary cortisol samples were collected at awakening, 30, 45, and 60 min thereafter, on two consecutive weekdays from a sample of adult Mexican Americans. Acculturative stress and self-reported health were assessed. Data were aggregated and analyzed (n = 89) using a mixed effects regression model and path analysis. Poorer self-reported health was associated with attenuated CAR profiles (primarily due to a diminished post-awakening rise in cortisol) predicted by both moderate and high levels of exposure to acculturative stress. Stress-induced alterations in the CAR mediated the relationship between exposure to acculturative stressors and self-reported health. Findings demonstrate that different levels of acculturative stress are associated with distinct CAR profiles and suggest the CAR is one possible biological pathway through which exposure to culturally unique stressors may be linked to health disparities.

Gene expression under chronic heat stress in populations of the mustard hill coral (Porites astreoides) from different thermal environments.

PubMed

Kenkel, C D; Meyer, E; Matz, M V

2013-08-01

Recent evidence suggests that corals can acclimatize or adapt to local stress factors through differential regulation of their gene expression. Profiling gene expression in corals from diverse environments can elucidate the physiological processes that may be responsible for maximizing coral fitness in their natural habitat and lead to a better understanding of the coral's capacity to survive the effects of global climate change. In an accompanying paper, we show that Porites astreoides from thermally different reef habitats exhibit distinct physiological responses when exposed to 6 weeks of chronic temperature stress in a common garden experiment. Here, we describe expression profiles obtained from the same corals for a panel of 9 previously reported and 10 novel candidate stress response genes identified in a pilot RNA-Seq experiment. The strongest expression change was observed in a novel candidate gene potentially involved in calcification, SLC26, a member of the solute carrier family 26 anion exchangers, which was down-regulated by 92-fold in bleached corals relative to controls. The most notable signature of divergence between coral populations was constitutive up-regulation of metabolic genes in corals from the warmer inshore location, including the gluconeogenesis enzymes pyruvate carboxylase and phosphoenolpyruvate carboxykinase and the lipid beta-oxidation enzyme acyl-CoA dehydrogenase. Our observations highlight several molecular pathways that were not previously implicated in the coral stress response and suggest that host management of energy budgets might play an adaptive role in holobiont thermotolerance. © 2013 John Wiley & Sons Ltd.

Tumour-associated and non-tumour-associated microbiota in colorectal cancer

PubMed Central

Flemer, Burkhardt; Lynch, Denise B; Brown, Jillian M R; Jeffery, Ian B; Ryan, Feargal J; Claesson, Marcus J; O'Riordain, Micheal; Shanahan, Fergus; O'Toole, Paul W

2017-01-01

Objective A signature that unifies the colorectal cancer (CRC) microbiota across multiple studies has not been identified. In addition to methodological variance, heterogeneity may be caused by both microbial and host response differences, which was addressed in this study. Design We prospectively studied the colonic microbiota and the expression of specific host response genes using faecal and mucosal samples (‘ON’ and ‘OFF’ the tumour, proximal and distal) from 59 patients undergoing surgery for CRC, 21 individuals with polyps and 56 healthy controls. Microbiota composition was determined by 16S rRNA amplicon sequencing; expression of host genes involved in CRC progression and immune response was quantified by real-time quantitative PCR. Results The microbiota of patients with CRC differed from that of controls, but alterations were not restricted to the cancerous tissue. Differences between distal and proximal cancers were detected and faecal microbiota only partially reflected mucosal microbiota in CRC. Patients with CRC can be stratified based on higher level structures of mucosal-associated bacterial co-abundance groups (CAGs) that resemble the previously formulated concept of enterotypes. Of these, Bacteroidetes Cluster 1 and Firmicutes Cluster 1 were in decreased abundance in CRC mucosa, whereas Bacteroidetes Cluster 2, Firmicutes Cluster 2, Pathogen Cluster and Prevotella Cluster showed increased abundance in CRC mucosa. CRC-associated CAGs were differentially correlated with the expression of host immunoinflammatory response genes. Conclusions CRC-associated microbiota profiles differ from those in healthy subjects and are linked with distinct mucosal gene-expression profiles. Compositional alterations in the microbiota are not restricted to cancerous tissue and differ between distal and proximal cancers. PMID:26992426

The role of personality in aggressive behaviour among individuals with intellectual disabilities.

PubMed

Chaïb, L S; Crocker, A G

2014-11-01

Aggressive behaviour is associated with certain personality traits in both the general population and among individuals with mental health problems, but little attention has been paid to the relationship between aggressive behaviour and personality among individuals with intellectual disabilities (ID). The aim of this study was to circumscribe personality profiles associated with aggressive behaviour among individuals with ID. In this cross-sectional study of 296 adults with mild or moderate ID, information on mental health, personality and aggressive behaviour was gathered through structured interviews with the ID participants and their case manager, and a review of client files. The results of the Reiss Profile were submitted to hierarchical cluster analysis method. Subsequently, the distribution of aggressive behaviour, sociodemographic characteristics and clinical characteristics across personality profiles was analysed. The analyses yielded seven distinct personality profiles in relation to patterns of aggressive behaviour: Pacifists, Socials, Confidents, Altruists, Conformists, Emotionals and Asocials. The identification of distinct personality profiles sheds light on the risk factors for aggressive behaviour, and suggests new approaches to improving diagnostic and intervention strategies. © 2013 The Authors. Journal of Intellectual Disability Research © 2013 John Wiley & Sons Ltd, MENCAP & IASSIDD.

Psychiatric reactions to continuous traumatic stress: A Latent Profile Analysis of two Israeli samples.

PubMed

Itzhaky, Liat; Gelkopf, Mark; Levin, Yafit; Stein, Jacob Y; Solomon, Zahava

2017-10-01

Many individuals worldwide are exposed to continuous traumatic stress (CTS). However, the psychiatric sequela of CTS and the relevance of posttraumatic stress disorder (PTSD) diagnostic criteria in this situation have yet to be determined. Filling this gap, the present study assessed psychiatric reactions to CTS and the relationship between such reactions and functional impairment among two representative samples of adults exposed to ongoing shelling over 6 (n=387) and 9 years (n=468). Assessment included PTSD symptomatology (i.e., intrusion, avoidance, hyperarousal), anxiety, somatization, and depression. Profile categorization aimed to underscore variations in symptom clustering and severity, and determine whether or not a profile is dominated by PTSD symptoms. Latent Profile analyses (LPA) of sample I revealed four distinct symptoms profiles: (1) 'symptomatically resilient'; (2) 'symptomatically low-moderate'; (3) 'symptomatically moderate-high'; and (4) 'symptomatically overall high'. LPA of sample II revealed three distinct symptoms profiles: (1) 'symptomatically resilient'; (2) 'symptomatically low-moderate'; (3) "symptomatically moderate-high". Moreover, profile variation was implicated in dysfunction. Consistent with studies focusing on single trauma exposure, the findings revealed that the most prevalent profile was the symptomatically resilient, indicating that most people exposed to CTS seem to evince a scarce number of psychiatric symptoms. Moreover, reactions to CTS proved broader than the existing PTSD symptomatology. Examining symptom dominance and severity in relation to impairment and dysfunction, and clinical considerations are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Convergence of the transcriptional responses to heat shock and singlet oxygen stresses.

PubMed

Dufour, Yann S; Imam, Saheed; Koo, Byoung-Mo; Green, Heather A; Donohue, Timothy J

2012-09-01

Cells often mount transcriptional responses and activate specific sets of genes in response to stress-inducing signals such as heat or reactive oxygen species. Transcription factors in the RpoH family of bacterial alternative σ factors usually control gene expression during a heat shock response. Interestingly, several α-proteobacteria possess two or more paralogs of RpoH, suggesting some functional distinction. We investigated the target promoters of Rhodobacter sphaeroides RpoH(I) and RpoH(II) using genome-scale data derived from gene expression profiling and the direct interactions of each protein with DNA in vivo. We found that the RpoH(I) and RpoH(II) regulons have both distinct and overlapping gene sets. We predicted DNA sequence elements that dictate promoter recognition specificity by each RpoH paralog. We found that several bases in the highly conserved TTG in the -35 element are important for activity with both RpoH homologs; that the T-9 position, which is over-represented in the RpoH(I) promoter sequence logo, is critical for RpoH(I)-dependent transcription; and that several bases in the predicted -10 element were important for activity with either RpoH(II) or both RpoH homologs. Genes that are transcribed by both RpoH(I) and RpoH(II) are predicted to encode for functions involved in general cell maintenance. The functions specific to the RpoH(I) regulon are associated with a classic heat shock response, while those specific to RpoH(II) are associated with the response to the reactive oxygen species, singlet oxygen. We propose that a gene duplication event followed by changes in promoter recognition by RpoH(I) and RpoH(II) allowed convergence of the transcriptional responses to heat and singlet oxygen stress in R. sphaeroides and possibly other bacteria.

Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain

PubMed Central

Liang, Winnie S.; Dunckley, Travis; Beach, Thomas G.; Grover, Andrew; Mastroeni, Diego; Walker, Douglas G.; Caselli, Richard J.; Kukull, Walter A.; McKeel, Daniel; Morris, John C.; Hulette, Christine; Schmechel, Donald; Alexander, Gene E.; Reiman, Eric M.; Rogers, Joseph; Stephan, Dietrich A.

2008-01-01

In this article, we have characterized and compared gene expression profiles from laser capture microdissected neurons in six functionally and anatomically distinct regions from clinically and histopathologically normal aged human brains. These regions, which are also known to be differentially vulnerable to the histopathological and metabolic features of Alzheimer’s disease (AD), include the entorhinal cortex and hippocampus (limbic and paralimbic areas vulnerable to early neurofibrillary tangle pathology in AD), posterior cingulate cortex (a paralimbic area vulnerable to early metabolic abnormalities in AD), temporal and prefrontal cortex (unimodal and heteromodal sensory association areas vulnerable to early neuritic plaque pathology in AD), and primary visual cortex (a primary sensory area relatively spared in early AD). These neuronal profiles will provide valuable reference information for future studies of the brain, in normal aging, AD and other neurological and psychiatric disorders. PMID:17077275

Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus.

PubMed

Josset, Laurence; Menachery, Vineet D; Gralinski, Lisa E; Agnihothram, Sudhakar; Sova, Pavel; Carter, Victoria S; Yount, Boyd L; Graham, Rachel L; Baric, Ralph S; Katze, Michael G

2013-04-30

A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus. Identification of a novel coronavirus causing fatal respiratory infection in humans raises concerns about a possible widespread outbreak of severe respiratory infection similar to the one caused by SARS-CoV. Using a human lung epithelial cell line and global transcriptomic profiling, we identified differences in the host response between HCoV-EMC and SARS-CoV. This enables rapid assessment of viral properties and the ability to anticipate possible differences in human clinical responses to HCoV-EMC and SARS-CoV. We used this information to predict potential effective drugs against HCoV-EMC, a method that could be more generally used to identify candidate therapeutics in future disease outbreaks. These data will help to generate hypotheses and make rapid advancements in characterizing this new virus.

Molecular profiling of ALDH1+ colorectal cancer stem cells reveals preferential activation of MAPK, FAK, and oxidative stress pro-survival signalling pathways

PubMed Central

Vishnubalaji, Radhakrishnan; Manikandan, Muthurangan; Fahad, Mohamed; Hamam, Rimi; Alfayez, Musaad; Kassem, Moustapha; Aldahmash, Abdullah; Alajez, Nehad M.

2018-01-01

Tumour heterogeneity leads to variable clinical response and inaccurate diagnostic and prognostic assessment. Cancer stem cells (CSCs) represent a subpopulation responsible for invasion, metastasis, therapeutic resistance, and recurrence in many human cancer types. However, the true identity of colorectal cancer (CRC) SCs remains elusive. Here, we aimed to characterize and define the gene expression portrait of CSCs in CRC-model SW403 cells. We found that ALDH+ positive cells are clonogenic and highly proliferative; their global gene expression profiling-based molecular signature revealed gene enrichment related to DNA damage, MAPK, FAK, oxidative stress response, and Wnt signalling. ALDH+ cells showed enhanced ROS stress resistance, whereas MAPK/FAK pathway pharmacologic inhibition limited their survival. Conversely, 5-fluorouracil increased the ALDH+ cell fraction among the SW403, HCT116 and SW620 CRC models. Notably, analysis of ALDH1A1 and POU5F1 expression levels in cohorts of 462 or 420 patients for overall (OS) or disease-free (DFS) survival, respectively, obtained from the Cancer Genome Atlas CRC dataset, revealed strong association between elevated expression and poor OS (p = 0.006) and poor DFS (p = 0.05), thus implicating ALDH1A1 and POU5F1 in CRC prognosis. Our data reveal distinct molecular signature of ALDH+ CSCs in CRC and suggest pathways relevant for successful targeted therapies and management of CRC. PMID:29568377

Long-term fertilization determines different metabolomic profiles and responses in saplings of three rainforest tree species with different adult canopy position.

PubMed

Gargallo-Garriga, Albert; Wright, S Joseph; Sardans, Jordi; Pérez-Trujillo, Míriam; Oravec, Michal; Večeřová, Kristýna; Urban, Otmar; Fernández-Martínez, Marcos; Parella, Teodor; Peñuelas, Josep

2017-01-01

Tropical rainforests are frequently limited by soil nutrient availability. However, the response of the metabolic phenotypic plasticity of trees to an increase of soil nutrient availabilities is poorly understood. We expected that increases in the ability of a nutrient that limits some plant processes should be detected by corresponding changes in plant metabolome profile related to such processes. We studied the foliar metabolome of saplings of three abundant tree species in a 15 year field NPK fertilization experiment in a Panamanian rainforest. The largest differences were among species and explained 75% of overall metabolome variation. The saplings of the large canopy species, Tetragastris panamensis, had the lowest concentrations of all identified amino acids and the highest concentrations of most identified secondary compounds. The saplings of the "mid canopy" species, Alseis blackiana, had the highest concentrations of amino acids coming from the biosynthesis pathways of glycerate-3P, oxaloacetate and α-ketoglutarate, and the saplings of the low canopy species, Heisteria concinna, had the highest concentrations of amino acids coming from the pyruvate synthesis pathways. The changes in metabolome provided strong evidence that different nutrients limit different species in different ways. With increasing P availability, the two canopy species shifted their metabolome towards larger investment in protection mechanisms, whereas with increasing N availability, the sub-canopy species increased its primary metabolism. The results highlighted the proportional distinct use of different nutrients by different species and the resulting different metabolome profiles in this high diversity community are consistent with the ecological niche theory.

Characterizing storm response and recovery using the beach change envelope: Fire Island, New York

USGS Publications Warehouse

Brenner, Owen T.; Lentz, Erika; Hapke, Cheryl J.; Henderson, Rachel; Wilson, Kathleen; Nelson, Timothy

2018-01-01

Hurricane Sandy at Fire Island, New York presented unique challenges in the quantification of storm impacts using traditional metrics of coastal change, wherein measured changes (shoreline, dune crest, and volume change) did not fully reflect the substantial changes in sediment redistribution following the storm. We used a time series of beach profile data at Fire Island, New York to define a new contour-based morphologic change metric, the Beach Change Envelope (BCE). The BCE quantifies changes to the upper portion of the beach likely to sustain measurable impacts from storm waves and capture a variety of storm and post-storm beach states. We evaluated the ability of the BCE to characterize cycles of beach change by relating it to a conceptual beach recovery regime, and demonstrated that BCE width and BCE height from the profile time series correlate well with established stages of recovery. We also investigated additional applications of this metric to capture impacts from storms and human modification by applying it to several post-storm historical datasets in which impacts varied considerably; Nor'Ida (2009), Hurricane Irene (2011), Hurricane Sandy (2012), and a 2009 community replenishment. In each case, the BCE captured distinctive upper beach morphologic change characteristic of these different beach building and erosional events. Analysis of the beach state at multiple profile locations showed spatial trends in recovery consistent with recent morphologic island evolution, which other studies have linked with sediment availability and the geologic framework. Ultimately we demonstrate a new way of more effectively characterizing beach response and recovery cycles to evaluate change along sandy coasts.

Cognitive Profile of Neurofibromatosis Type 1: Rethinking Nonverbal Learning Disabilities

ERIC Educational Resources Information Center

Cutting, Laurie E.; Clements, Amy M.; Lightman, Andrea D.; Yerby-Hammack, Pamula D.; Denckla, Martha Bridge

2004-01-01

The cognitive profiles of children with Neurofibromatosis Type 1 (NF-1) have many similarities to those observed in learning disabilities in the general school population, as well as some distinct features. Approximately 30-65 percent of children with NF-1 have learning disabilities; most commonly, they have language and reading disabilities,…

Which Emotional Profiles Exhibit the Best Learning Outcomes? A Person-Centered Analysis of Students' Academic Emotions

ERIC Educational Resources Information Center

Ganotice, Fraide A., Jr.; Datu, Jesus Alfonso D.; King, Ronnel B.

2016-01-01

Previous studies on academic emotions have mostly used variable-centered approaches. Although these studies have elucidated the relationships between academic emotions and key academic outcomes, they cannot identify naturally-occurring groups of students defined by distinct academic emotion profiles. In this study, we adopted a person-centered…

Association between Mutation Spectra and Stable and Unstable DNA Adduct Profiles in Salmonella for Benzo[a]pyrene and Dibenzo[a.l]pyrene

EPA Science Inventory

Benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) are two polycyclic aromatic hydrocarbons (PAHs) that exhibit distinctly different mutagenicity and carcinogenicity profiles. Although some studies show that these PAHs produce unstable DNA adducts, conflicting data and arguments ha...

Exuberant and Inhibited Children: Person-Centered Profiles and Links to Social Adjustment

ERIC Educational Resources Information Center

Dollar, Jessica M.; Stifter, Cynthia A.; Buss, Kristin A.

2017-01-01

The current study aimed to substantiate and extend our understanding regarding the existence and developmental pathways of 3 distinct temperament profiles--exuberant, inhibited, and average approach--in a sample of 3.5-year-old children (n = 121). The interactions between temperamental styles and specific types of effortful control, inhibitory…

Exploring Different Types of Academic Delayers: A Latent Profile Analysis

ERIC Educational Resources Information Center

Grunschel, Carola; Patrzek, Justine; Fries, Stefan

2013-01-01

In this study, we explored whether there are different types of academic delayers (i.e., types of students who delay academic tasks). Latent profile analysis based on 554 university students' reasons for academic delay revealed four distinct types: inconspicuous, successful pressure-seeking, worried/anxious, and discontent with studies. The types…

Chemical profiling of two congeneric sea mat corals along the Brazilian coast: adaptive and functional patterns.

PubMed

Costa-Lotufo, L V; Carnevale-Neto, F; Trindade-Silva, A E; Silva, R R; Silva, G G Z; Wilke, D V; Pinto, F C L; Sahm, B D B; Jimenez, P C; Mendonça, J N; Lotufo, T M C; Pessoa, O D L; Lopes, N P

2018-02-20

Metabolomic profiles were explored to understand environmental and taxonomic influences on the metabolism of two congeneric zoanthids, Palythoa caribaeorum and P. variabilis, collected across distinct geographical ranges. Integrated mass spectrometry data suggested the major influence of geographical location on chemical divergence when compared to species differentiation.

Investigation of the aroma of commercial peach (Prunus persica L. Batsch) types by Proton Transfer Reaction-Mass Spectrometry (PTR-MS) and sensory analysis.

PubMed

Bianchi, Tiago; Weesepoel, Yannick; Koot, Alex; Iglesias, Ignasi; Eduardo, Iban; Gratacós-Cubarsí, Marta; Guerrero, Luis; Hortós, Maria; van Ruth, Saskia

2017-09-01

The aim of this study was to investigate the aroma and sensory profiles of various types of peaches (Prunus persica L. Batsch.). Forty-three commercial cultivars comprising peaches, flat peaches, nectarines, and canning peaches (pavías) were grown over two consecutive harvest years. Fruits were assessed for chemical aroma and sensory profiles. Chemical aroma profile was obtained by proton transfer reaction-mass spectrometry (PTR-MS) and spectral masses were tentatively identified with PTR-Time of Flight-MS (PTR-Tof-MS). Sensory analysis was performed at commercial maturity considering seven aroma/flavor attributes. The four types of peaches showed both distinct chemical aroma and sensory profiles. Flat peaches and canning peaches showed most distinct patterns according to discriminant analysis. The sensory data were related to the volatile compounds by partial least square regression. γ-Hexalactone, γ-octalactone, hotrienol, acetic acid and ethyl acetate correlated positively, and benzeneacetaldehyde, trimethylbenzene and acetaldehyde negatively to the intensities of aroma and ripe fruit sensory scores. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tropospheric Ozonesonde Profiles at Long-term U.S. Monitoring Sites: 1. A Climatology Based on Self-Organizing Maps

NASA Technical Reports Server (NTRS)

Stauffer, Ryan M.; Thompson, Anne M.; Young, George S.

2016-01-01

Sonde-based climatologies of tropospheric ozone (O3) are vital for developing satellite retrieval algorithms and evaluating chemical transport model output. Typical O3 climatologies average measurements by latitude or region, and season. A recent analysis using self-organizing maps (SOM) to cluster ozonesondes from two tropical sites found that clusters of O3 mixing ratio profiles are an excellent way to capture O3variability and link meteorological influences to O3 profiles. Clusters correspond to distinct meteorological conditions, e.g., convection, subsidence, cloud cover, and transported pollution. Here the SOM technique is extended to four long-term U.S. sites (Boulder, CO; Huntsville, AL; Trinidad Head, CA; and Wallops Island, VA) with4530 total profiles. Sensitivity tests on k-means algorithm and SOM justify use of 3 3 SOM (nine clusters). Ateach site, SOM clusters together O3 profiles with similar tropopause height, 500 hPa height temperature, and amount of tropospheric and total column O3. Cluster means are compared to monthly O3 climatologies.For all four sites, near-tropopause O3 is double (over +100 parts per billion by volume; ppbv) the monthly climatological O3 mixing ratio in three clusters that contain 1316 of profiles, mostly in winter and spring.Large midtropospheric deviations from monthly means (6 ppbv, +710 ppbv O3 at 6 km) are found in two of the most populated clusters (combined 3639 of profiles). These two clusters contain distinctly polluted(summer) and clean O3 (fall-winter, high tropopause) profiles, respectively. As for tropical profiles previously analyzed with SOM, O3 averages are often poor representations of U.S. O3 profile statistics.

Tropospheric ozonesonde profiles at long-term U.S. monitoring sites: 1. A climatology based on self-organizing maps

PubMed Central

Stauffer, Ryan M.; Thompson, Anne M.; Young, George S.

2018-01-01

Sonde-based climatologies of tropospheric ozone (O3) are vital for developing satellite retrieval algorithms and evaluating chemical transport model output. Typical O3 climatologies average measurements by latitude or region, and season. Recent analysis using self-organizing maps (SOM) to cluster ozonesondes from two tropical sites found clusters of O3 mixing ratio profiles are an excellent way to capture O3 variability and link meteorological influences to O3 profiles. Clusters correspond to distinct meteorological conditions, e.g. convection, subsidence, cloud cover, and transported pollution. Here, the SOM technique is extended to four long-term U.S. sites (Boulder, CO; Huntsville, AL; Trinidad Head, CA; Wallops Island, VA) with 4530 total profiles. Sensitivity tests on k-means algorithm and SOM justify use of 3×3 SOM (nine clusters). At each site, SOM clusters together O3 profiles with similar tropopause height, 500 hPa height/temperature, and amount of tropospheric and total column O3. Cluster means are compared to monthly O3 climatologies. For all four sites, near-tropopause O3 is double (over +100 parts per billion by volume; ppbv) the monthly climatological O3 mixing ratio in three clusters that contain 13 – 16% of profiles, mostly in winter and spring. Large mid-tropospheric deviations from monthly means (−6 ppbv, +7 – 10 ppbv O3 at 6 km) are found in two of the most populated clusters (combined 36 – 39% of profiles). These two clusters contain distinctly polluted (summer) and clean O3 (fall-winter, high tropopause) profiles, respectively. As for tropical profiles previously analyzed with SOM, O3 averages are often poor representations of U.S. O3 profile statistics. PMID:29619288

Tropospheric ozonesonde profiles at long-term U.S. monitoring sites: 1. A climatology based on self-organizing maps.

PubMed

Stauffer, Ryan M; Thompson, Anne M; Young, George S

2016-02-16

Sonde-based climatologies of tropospheric ozone (O 3 ) are vital for developing satellite retrieval algorithms and evaluating chemical transport model output. Typical O 3 climatologies average measurements by latitude or region, and season. Recent analysis using self-organizing maps (SOM) to cluster ozonesondes from two tropical sites found clusters of O 3 mixing ratio profiles are an excellent way to capture O 3 variability and link meteorological influences to O 3 profiles. Clusters correspond to distinct meteorological conditions, e.g. convection, subsidence, cloud cover, and transported pollution. Here, the SOM technique is extended to four long-term U.S. sites (Boulder, CO; Huntsville, AL; Trinidad Head, CA; Wallops Island, VA) with 4530 total profiles. Sensitivity tests on k-means algorithm and SOM justify use of 3×3 SOM (nine clusters). At each site, SOM clusters together O 3 profiles with similar tropopause height, 500 hPa height/temperature, and amount of tropospheric and total column O 3 . Cluster means are compared to monthly O 3 climatologies. For all four sites, near-tropopause O 3 is double (over +100 parts per billion by volume; ppbv) the monthly climatological O 3 mixing ratio in three clusters that contain 13 - 16% of profiles, mostly in winter and spring. Large mid-tropospheric deviations from monthly means (-6 ppbv, +7 - 10 ppbv O 3 at 6 km) are found in two of the most populated clusters (combined 36 - 39% of profiles). These two clusters contain distinctly polluted (summer) and clean O 3 (fall-winter, high tropopause) profiles, respectively. As for tropical profiles previously analyzed with SOM, O 3 averages are often poor representations of U.S. O 3 profile statistics.

Functional Status, Quality of Life, and Costs Associated With Fibromyalgia Subgroups: A Latent Profile Analysis.

PubMed

Luciano, Juan V; Forero, Carlos G; Cerdà-Lafont, Marta; Peñarrubia-María, María Teresa; Fernández-Vergel, Rita; Cuesta-Vargas, Antonio I; Ruíz, José M; Rozadilla-Sacanell, Antoni; Sirvent-Alierta, Elena; Santo-Panero, Pilar; García-Campayo, Javier; Serrano-Blanco, Antoni; Pérez-Aranda, Adrián; Rubio-Valera, María

2016-10-01

Although fibromyalgia syndrome (FM) is considered a heterogeneous condition, there is no generally accepted subgroup typology. We used hierarchical cluster analysis and latent profile analysis to replicate Giesecke's classification in Spanish FM patients. The second aim was to examine whether the subgroups differed in sociodemographic characteristics, functional status, quality of life, and in direct and indirect costs. A total of 160 FM patients completed the following measures for cluster derivation: the Center for Epidemiological Studies-Depression Scale, the Trait Anxiety Inventory, the Pain Catastrophizing Scale, and the Control over Pain subscale. Pain threshold was measured with a sphygmomanometer. In addition, the Fibromyalgia Impact Questionnaire-Revised, the EuroQoL-5D-3L, and the Client Service Receipt Inventory were administered for cluster validation. Two distinct clusters were identified using hierarchical cluster analysis ("hypersensitive" group, 69.8% and "functional" group, 30.2%). In contrast, the latent profile analysis goodness-of-fit indices supported the existence of 3 FM patient profiles: (1) a "functional" profile (28.1%) defined as moderate tenderness, distress, and pain catastrophizing; (2) a "dysfunctional" profile (45.6%) defined by elevated tenderness, distress, and pain catastrophizing; and (3) a "highly dysfunctional and distressed" profile (26.3%) characterized by elevated tenderness and extremely high distress and catastrophizing. We did not find significant differences in sociodemographic characteristics between the 2 clusters or among the 3 profiles. The functional profile was associated with less impairment, greater quality of life, and lower health care costs. We identified 3 distinct profiles which accounted for the heterogeneity of FM patients. Our findings might help to design tailored interventions for FM patients.

The dissociative post-traumatic stress disorder (PTSD) subtype: A treatment outcome cohort study in veterans with PTSD.

PubMed

Haagen, Joris F G; van Rijn, Allison; Knipscheer, Jeroen W; van der Aa, Niels; Kleber, Rolf J

2018-06-01

Dissociation is a prevalent phenomenon among veterans with post-traumatic stress disorder (PTSD) that may interfere with the effectiveness of treatment. This study aimed to replicate findings of a dissociative PTSD subtype, to identify corresponding patterns in coping style, symptom type, and symptom severity, and to investigate its impact on post-traumatic symptom improvement. Latent profile analysis (LPA) was applied to baseline data from 330 predominantly (97%) male treatment-seeking veterans (mean age 39.5 years) with a probable PTSD. Multinomial logistic models were used to identify predictors of dissociative PTSD. Eighty veterans with PTSD that commenced with psychotherapy were invited for a follow-up measure after 6 months. The majority (n = 64, 80% response rate) completed the follow-up measure. Changes in post-traumatic stress between baseline and follow-up were explored as a continuous distal outcome. Latent profile analysis revealed four distinct patient profiles: 'low' (12.9%), 'moderate' (33.2%), 'severe' (45.1%), and 'dissociative' (8.8%) PTSD. The dissociative PTSD profile was characterized by more severe pathology levels, though not post-traumatic reactions symptom severity. Veterans with dissociative PTSD benefitted equally from PTSD treatment as veterans with non-dissociative PTSD with similar symptom severity. Within a sample of veterans with PTSD, a subsample of severely dissociative veterans was identified, characterized by elevated severity levels on pathology dimensions. The dissociative PTSD subtype did not negatively impact PTSD treatment. The present findings confirmed the existence of a distinct subgroup veterans that fit the description of dissociative PTSD. Patients with dissociative PTSD subtype symptoms uniquely differed from patients with non-dissociative PTSD in the severity of several psychopathology dimensions. Dissociative and non-dissociative PTSD patients with similar post-traumatic severity levels showed similar levels of improvement after PTSD treatment. The observational design and small sample size caution interpretation of the treatment outcome data. The IES-R questionnaire does not assess all PTSD DSM-IV diagnostic criteria (14 of 17), although it is considered a valid measure for an indication of PTSD. © 2018 The British Psychological Society.

The effect of inhibitory signals on the priming of drug-hapten-specific T-cells that express distinct Vβ receptors

PubMed Central

Gibson, Andrew; Faulkner, Lee; Lichtenfels, Maike; Ogese, Monday; Al-Attar, Zaid; Alfirevic, Ana; Esser, Philipp R.; Martin, Stefan F.; Pirmohamed, Munir; Park, B. Kevin; Naisbitt, Dean J.

2017-01-01

Drug hypersensitivity involves the activation of T-cells in an HLA allele-restricted manner. Since the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T-cell response. Thus, we have utilized a T-cell priming assay and nitroso sulfamethoxazole (SMX-NO) as a model antigen to investigate (1) the activation of specific T-cell receptor (TCR)Vβ subtypes, (2) the impact of PD-1, CTLA4 and TIM-3 co-inhibitory signalling on activation of naïve and memory T-cells and (3) the ability of Tregs to prevent responses. An expansion of the TCR repertoire was observed for nine different Vβ subtypes, while spectratyping revealed that SMX-NO-specific T-cell responses are controlled by public TCRs present in all individuals alongside private TCR repertoires specific to each individual. We proceeded to evaluate the extent to which the activation of these TCR Vβ-restricted antigen-specific T-cell responses is governed by regulatory signals. Blockade of PDL-1/CTLA4 signalling dampened activation of SMX-NO-specific naïve and memory T-cells, while blockade of TIM-3 produced no effect. PD-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug-induced T-cell activation and expression of each receptor was enhanced on dividing T-cells. As these receptors are also expressed on Tregs, Treg-mediated suppression of SMX-NO-induced T-cell activation was investigated. Tregs significantly dampened the priming of T-cells. In conclusion, our findings demonstrate that distinct TCR Vβ subtypes, dysregulation of co-inhibitory signalling pathways and dysfunctional Tregs may influence predisposition to hypersensitivity. PMID:28687658

Maternal immune response to helminth infection during pregnancy determines offspring susceptibility to allergic airway inflammation.

PubMed

Straubinger, Kathrin; Paul, Sabine; Prazeres da Costa, Olivia; Ritter, Manuel; Buch, Thorsten; Busch, Dirk H; Layland, Laura E; Prazeres da Costa, Clarissa U

2014-12-01

Schistosomiasis, a chronic helminth infection, elicits distinct immune responses within the host, ranging from an initial TH1 and subsequent TH2 phase to a regulatory state, and is associated with dampened allergic reactions within the host. We sought to evaluate whether non-transplacental helminth infection during pregnancy alters the offspring's susceptibility to allergy. Ovalbumin-induced allergic airway inflammation was analyzed in offspring from Schistosoma mansoni-infected mothers mated during the TH1, TH2, or regulatory phase of infection. Embryos derived from in vitro fertilized oocytes of acutely infected females were transferred into uninfected foster mice to determine the role of placental environment. The fetomaternal unit was further characterized by helminth-specific immune responses and microarray analyses. Eventually, IFN-γ-deficient mice were infected to evaluate the role of this predominant cytokine on the offspring's allergy phenotype. We demonstrate that offspring from schistosome-infected mothers that were mated in the TH1 and regulatory phases, but not the TH2 immune phase, are protected against the onset of allergic airway inflammation. Interestingly, these effects were associated with distinctly altered schistosome-specific cytokine and gene expression profiles within the fetomaternal interface. Furthermore, we identified that it is not the transfer of helminth antigens but rather maternally derived IFN-γ during the acute phase of infection that is essential for the progeny's protective immune phenotype. Overall, we present a novel immune phase-dependent coherency between the maternal immune responses during schistosomiasis and the progeny's predisposition to allergy. Therefore, we propose to include helminth-mediated transmaternal immune modulation into the expanded hygiene hypothesis. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Distinct transcriptome responses to water limitation in isohydric and anisohydric grapevine cultivars.

PubMed

Dal Santo, Silvia; Palliotti, Alberto; Zenoni, Sara; Tornielli, Giovanni Battista; Fasoli, Marianna; Paci, Paola; Tombesi, Sergio; Frioni, Tommaso; Silvestroni, Oriana; Bellincontro, Andrea; d'Onofrio, Claudio; Matarese, Fabiola; Gatti, Matteo; Poni, Stefano; Pezzotti, Mario

2016-10-20

Grapevine (Vitis vinifera L.) is an economically important crop with a wide geographical distribution, reflecting its ability to grow successfully in a range of climates. However, many vineyards are located in regions with seasonal drought, and these are often predicted to be global climate change hotspots. Climate change affects the entire physiology of grapevine, with strong effects on yield, wine quality and typicity, making it difficult to produce berries of optimal enological quality and consistent stability over the forthcoming decades. Here we investigated the reactions of two grapevine cultivars to water stress, the isohydric variety Montepulciano and the anisohydric variety Sangiovese, by examining physiological and molecular perturbations in the leaf and berry. A multidisciplinary approach was used to characterize the distinct stomatal behavior of the two cultivars and its impact on leaf and berry gene expression. Positive associations were found among the photosynthetic, physiological and transcriptional modifications, and candidate genes encoding master regulators of the water stress response were identified using an integrated approach based on the analysis of topological co-expression network properties. In particular, the genome-wide transcriptional study indicated that the isohydric behavior relies upon the following responses: i) faster transcriptome response after stress imposition; ii) faster abscisic acid-related gene modulation; iii) more rapid expression of heat shock protein (HSP) genes and iv) reversion of gene-expression profile at rewatering. Conversely, that reactive oxygen species (ROS)-scavenging enzymes, molecular chaperones and abiotic stress-related genes were induced earlier and more strongly in the anisohydric cultivar. Overall, the present work found original evidence of a molecular basis for the proposed classification between isohydric and anisohydric grapevine genotypes.

Methodology and evaluation of intracranial pressure response in rats exposed to complex shock waves.

PubMed

Dal Cengio Leonardi, Alessandra; Keane, Nickolas J; Hay, Kathryn; Ryan, Anne G; Bir, Cynthia A; VandeVord, Pamela J

2013-12-01

Studies on blast neurotrauma have focused on investigating the effects of exposure to free-field blast representing the simplest form of blast threat scenario without considering any reflecting surfaces. However, in reality personnel are often located within enclosures or nearby reflecting walls causing a complex blast environment, that is, involving shock reflections and/or compound waves from different directions. The purpose of this study was to design a complex wave testing system and perform a preliminary investigation of the intracranial pressure (ICP) response of rats exposed to a complex blast wave environment (CBWE). The effects of head orientation in the same environment were also explored. Furthermore, since it is hypothesized that exposure to a CBWE would be more injurious as compared to a free-field blast wave environment (FFBWE), a histological comparison of hippocampal injury (cleaved caspase-3 and glial fibrillary acidic protein (GFAP)) was conducted in both environments. Results demonstrated that, regardless of orientation, peak ICP values were significantly elevated over the peak static air overpressure. Qualitative differences could be noticed compared to the ICP response in rats exposed to simulated FFBWE. In the CBWE scenario, after the initial loading the skull/brain system was not allowed to return to rest and was loaded again reaching high ICP values. Furthermore, results indicated consistent and distinct ICP-time profiles according to orientation, as well as distinctive values of impulse associated with each orientation. Histologically, cleaved caspase-3 positive cells were significantly increased in the CBWE as compared to the FFBWE. Overall, these findings suggest that the geometry of the skull and the way sutures are distributed in the rats are responsible for the difference in the stresses observed. Moreover, this increase stress contributes to correlation of increased injury in the CBWE.

Allergic Asthmatics Show Divergent Lipid Mediator Profiles from Healthy Controls Both at Baseline and following Birch Pollen Provocation

PubMed Central

Lundström, Susanna L.; Yang, Jun; Källberg, Henrik J.; Thunberg, Sarah; Gafvelin, Guro; Haeggström, Jesper Z.; Grönneberg, Reidar; Grunewald, Johan; van Hage, Marianne; Hammock, Bruce D.; Eklund, Anders; Wheelock, Åsa M.; Wheelock, Craig E.

2012-01-01

Background Asthma is a respiratory tract disorder characterized by airway hyper-reactivity and chronic inflammation. Allergic asthma is associated with the production of allergen-specific IgE and expansion of allergen-specific T-cell populations. Progression of allergic inflammation is driven by T-helper type 2 (Th2) mediators and is associated with alterations in the levels of lipid mediators. Objectives Responses of the respiratory system to birch allergen provocation in allergic asthmatics were investigated. Eicosanoids and other oxylipins were quantified in the bronchoalveolar lumen to provide a measure of shifts in lipid mediators associated with allergen challenge in allergic asthmatics. Methods Eighty-seven lipid mediators representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened via LC-MS/MS following off-line extraction of bronchoalveolar lavage fluid (BALF). Multivariate statistics using OPLS were employed to interrogate acquired oxylipin data in combination with immunological markers. Results Thirty-two oxylipins were quantified, with baseline asthmatics possessing a different oxylipin profile relative to healthy individuals that became more distinct following allergen provocation. The most prominent differences included 15-LOX-derived ω-3 and ω-6 oxylipins. Shared-and-Unique-Structures (SUS)-plot modeling showed a correlation (R2 = 0.7) between OPLS models for baseline asthmatics (R2Y[cum] = 0.87, Q2[cum] = 0.51) and allergen-provoked asthmatics (R2Y[cum] = 0.95, Q2[cum] = 0.73), with the majority of quantified lipid mediators and cytokines contributing equally to both groups. Unique structures for allergen provocation included leukotrienes (LTB4 and 6-trans-LTB4), CYP-derivatives of linoleic acid (epoxides/diols), and IL-10. Conclusions Differences in asthmatic relative to healthy profiles suggest a role for 15-LOX products of both ω-6 and ω-3 origin in allergic inflammation. Prominent differences at baseline levels indicate that non-symptomatic asthmatics are subject to an underlying inflammatory condition not observed with other traditional mediators. Results suggest that oxylipin profiling may provide a sensitive means of characterizing low-level inflammation and that even individuals with mild disease display distinct phenotypic profiles, which may have clinical ramifications for disease. PMID:22438998

The neurologic findings in Taybi-Linder syndrome (MOPD I/III): case report and review of the literature.

PubMed

Pierce, Melinda J; Morse, Richard P

2012-03-01

Taybi-Linder syndrome, also known as microcephalic osteodysplastic primordial dwarfism types I and III, is a rare disorder with presumed autosomal recessive inheritance. It is characterized by intrauterine growth retardation, distinctive bone dysplasia, and central nervous system malformations. We present two siblings with Taybi-Linder syndrome, with an emphasis on the neurological profile in this disease, which includes brain malformations, intractable epilepsy, sensory deficits, profound cognitive deficits, and neuroendocrine dysfunction. We also present distinctive correlative neuroimaging (MRI) and electroencephalographic (EEG) findings. Increased knowledge of the neurological profile of Taybi-Linder syndrome may be helpful for clinicians and genetic counselors managing these patients. Copyright © 2012 Wiley Periodicals, Inc.

The Staphylococcus aureus Two-Component System AgrAC Displays Four Distinct Genomic Arrangements That Delineate Genomic Virulence Factor Signatures

PubMed Central

Choudhary, Kumari S.; Mih, Nathan; Monk, Jonathan; Kavvas, Erol; Yurkovich, James T.; Sakoulas, George; Palsson, Bernhard O.

2018-01-01

Two-component systems (TCSs) consist of a histidine kinase and a response regulator. Here, we evaluated the conservation of the AgrAC TCS among 149 completely sequenced Staphylococcus aureus strains. It is composed of four genes: agrBDCA. We found that: (i) AgrAC system (agr) was found in all but one of the 149 strains, (ii) the agr positive strains were further classified into four agr types based on AgrD protein sequences, (iii) the four agr types not only specified the chromosomal arrangement of the agr genes but also the sequence divergence of AgrC histidine kinase protein, which confers signal specificity, (iv) the sequence divergence was reflected in distinct structural properties especially in the transmembrane region and second extracellular binding domain, and (v) there was a strong correlation between the agr type and the virulence genomic profile of the organism. Taken together, these results demonstrate that bioinformatic analysis of the agr locus leads to a classification system that correlates with the presence of virulence factors and protein structural properties. PMID:29887846

Transcriptional and functional profiling defines human small intestinal macrophage subsets.

PubMed

Bujko, Anna; Atlasy, Nader; Landsverk, Ole J B; Richter, Lisa; Yaqub, Sheraz; Horneland, Rune; Øyen, Ole; Aandahl, Einar Martin; Aabakken, Lars; Stunnenberg, Hendrik G; Bækkevold, Espen S; Jahnsen, Frode L

2018-02-05

Macrophages (Mfs) are instrumental in maintaining immune homeostasis in the intestine, yet studies on the origin and heterogeneity of human intestinal Mfs are scarce. Here, we identified four distinct Mf subpopulations in human small intestine (SI). Assessment of their turnover in duodenal transplants revealed that all Mf subsets were completely replaced over time; Mf1 and Mf2, phenotypically similar to peripheral blood monocytes (PBMos), were largely replaced within 3 wk, whereas two subsets with features of mature Mfs, Mf3 and Mf4, exhibited significantly slower replacement. Mf3 and Mf4 localized differently in SI; Mf3 formed a dense network in mucosal lamina propria, whereas Mf4 was enriched in submucosa. Transcriptional analysis showed that all Mf subsets were markedly distinct from PBMos and dendritic cells. Compared with PBMos, Mf subpopulations showed reduced responsiveness to proinflammatory stimuli but were proficient at endocytosis of particulate and soluble material. These data provide a comprehensive analysis of human SI Mf population and suggest a precursor-progeny relationship with PBMos. © 2018 Bujko et al.

A Simple Network Architecture Accounts for Diverse Reward Time Responses in Primary Visual Cortex

PubMed Central

Hussain Shuler, Marshall G.; Shouval, Harel Z.

2015-01-01

Many actions performed by animals and humans depend on an ability to learn, estimate, and produce temporal intervals of behavioral relevance. Exemplifying such learning of cued expectancies is the observation of reward-timing activity in the primary visual cortex (V1) of rodents, wherein neural responses to visual cues come to predict the time of future reward as behaviorally experienced in the past. These reward-timing responses exhibit significant heterogeneity in at least three qualitatively distinct classes: sustained increase or sustained decrease in firing rate until the time of expected reward, and a class of cells that reach a peak in firing at the expected delay. We elaborate upon our existing model by including inhibitory and excitatory units while imposing simple connectivity rules to demonstrate what role these inhibitory elements and the simple architectures play in sculpting the response dynamics of the network. We find that simply adding inhibition is not sufficient for obtaining the different distinct response classes, and that a broad distribution of inhibitory projections is necessary for obtaining peak-type responses. Furthermore, although changes in connection strength that modulate the effects of inhibition onto excitatory units have a strong impact on the firing rate profile of these peaked responses, the network exhibits robustness in its overall ability to predict the expected time of reward. Finally, we demonstrate how the magnitude of expected reward can be encoded at the expected delay in the network and how peaked responses express this reward expectancy. SIGNIFICANCE STATEMENT Heterogeneity in single-neuron responses is a common feature of neuronal systems, although sometimes, in theoretical approaches, it is treated as a nuisance and seldom considered as conveying a different aspect of a signal. In this study, we focus on the heterogeneous responses in the primary visual cortex of rodents trained with a predictable delayed reward time. We describe under what conditions this heterogeneity can arise by self-organization, and what information it can convey. This study, while focusing on a specific system, provides insight onto how heterogeneity can arise in general while also shedding light onto mechanisms of reinforcement learning using realistic biological assumptions. PMID:26377457

Transcriptional programming during cell wall maturation in the expanding Arabidopsis stem.

PubMed

Hall, Hardy; Ellis, Brian

2013-01-25

Plant cell walls are complex dynamic structures that play a vital role in coordinating the directional growth of plant tissues. The rapid elongation of the inflorescence stem in the model plant Arabidopsis thaliana is accompanied by radical changes in cell wall structure and chemistry, but analysis of the underlying mechanisms and identification of the genes that are involved has been hampered by difficulties in accurately sampling discrete developmental states along the developing stem. By creating stem growth kinematic profiles for individual expanding Arabidopsis stems we have been able to harvest and pool developmentally-matched tissue samples, and to use these for comparative analysis of global transcript profiles at four distinct phases of stem growth: the period of elongation rate increase, the point of maximum growth rate, the point of stem growth cessation and the fully matured stem. The resulting profiles identify numerous genes whose expression is affected as the stem tissues pass through these defined growth transitions, including both novel loci and genes identified in earlier studies. Of particular note is the preponderance of highly active genes associated with secondary cell wall deposition in the region of stem growth cessation, and of genes associated with defence and stress responses in the fully mature stem. The use of growth kinematic profiling to create tissue samples that are accurately positioned along the expansion growth continuum of Arabidopsis inflorescence stems establishes a new standard for transcript profiling analyses of such tissues. The resulting expression profiles identify a substantial number of genes whose expression is correlated for the first time with rapid cell wall extension and subsequent fortification, and thus provide an important new resource for plant biologists interested in gene discovery related to plant biomass accumulation.

Influence of nitrogen substrates and substrate C:N ratios on the nitrogen isotopic composition of amino acids from the marine bacterium Vibrio harveyi

NASA Astrophysics Data System (ADS)

Maki, K.; Ohkouchi, N.; Chikaraishi, Y.; Fukuda, H.; Miyajima, T.; Nagata, T.

2014-09-01

Nitrogen (N) isotopic compositions of individual hydrolysable amino acids (δ15NAAs) in N pools have been increasingly used for trophic position assessment and evaluation of sources and transformation processes of organic matter in marine environments. However, there are limited data about variability in δ15NAAs patterns and how this variability influences marine bacteria, an important mediator of trophic transfer and organic matter transformation. We explored whether marine bacterial δ15NAAs profiles change depending on the type and C:N ratio of the substrate. The δ15NAAs profile of a marine bacterium, Vibrio harveyi, was examined using medium containing either glutamate, alanine or ammonium as the N source [substrate C:N ratios (range, 3 to 20) were adjusted with glucose]. The data were interpreted as a reflection of isotope fractionations associated with de novo synthesis of amino acids by bacteria. Principal component analysis (PCA) using the δ15N offset values normalized to glutamate + glutamine δ15N revealed that δ15NAAs profiles differed depending on the N source and C:N ratio of the substrate. High variability in the δ15N offset of alanine and valine largely explained this bacterial δ15NAAs profile variability. PCA was also conducted using bacterial and phytoplankton (cyanobacteria and eukaryotic algae) δ15NAAs profile data reported previously. The results revealed that bacterial δ15NAAs patterns were distinct from those of phytoplankton. Therefore, the δ15NAAs profile is a useful indicator of biochemical responses of bacteria to changes in substrate conditions, serving as a potentially useful method for identifying organic matter sources in marine environments.

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

Bayesian hierarchical piecewise regression models: a tool to detect trajectory divergence between groups in long-term observational studies.

PubMed

Buscot, Marie-Jeanne; Wotherspoon, Simon S; Magnussen, Costan G; Juonala, Markus; Sabin, Matthew A; Burgner, David P; Lehtimäki, Terho; Viikari, Jorma S A; Hutri-Kähönen, Nina; Raitakari, Olli T; Thomson, Russell J

2017-06-06

Bayesian hierarchical piecewise regression (BHPR) modeling has not been previously formulated to detect and characterise the mechanism of trajectory divergence between groups of participants that have longitudinal responses with distinct developmental phases. These models are useful when participants in a prospective cohort study are grouped according to a distal dichotomous health outcome. Indeed, a refined understanding of how deleterious risk factor profiles develop across the life-course may help inform early-life interventions. Previous techniques to determine between-group differences in risk factors at each age may result in biased estimate of the age at divergence. We demonstrate the use of Bayesian hierarchical piecewise regression (BHPR) to generate a point estimate and credible interval for the age at which trajectories diverge between groups for continuous outcome measures that exhibit non-linear within-person response profiles over time. We illustrate our approach by modeling the divergence in childhood-to-adulthood body mass index (BMI) trajectories between two groups of adults with/without type 2 diabetes mellitus (T2DM) in the Cardiovascular Risk in Young Finns Study (YFS). Using the proposed BHPR approach, we estimated the BMI profiles of participants with T2DM diverged from healthy participants at age 16 years for males (95% credible interval (CI):13.5-18 years) and 21 years for females (95% CI: 19.5-23 years). These data suggest that a critical window for weight management intervention in preventing T2DM might exist before the age when BMI growth rate is naturally expected to decrease. Simulation showed that when using pairwise comparison of least-square means from categorical mixed models, smaller sample sizes tended to conclude a later age of divergence. In contrast, the point estimate of the divergence time is not biased by sample size when using the proposed BHPR method. BHPR is a powerful analytic tool to model long-term non-linear longitudinal outcomes, enabling the identification of the age at which risk factor trajectories diverge between groups of participants. The method is suitable for the analysis of unbalanced longitudinal data, with only a limited number of repeated measures per participants and where the time-related outcome is typically marked by transitional changes or by distinct phases of change over time.

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation

PubMed Central

2012-01-01

Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors. PMID:22731117

Subjective reactions to cocaine and marijuana are associated with abuse and dependence.

PubMed

Grant, Julia D; Scherrer, Jeffrey F; Lyons, Michael J; Tsuang, Ming; True, William R; Bucholz, Kathleen K

2005-09-01

Subjective effects of marijuana and cocaine use are associated with amount of drug use and potentially with risk of abuse and dependence. We used Latent Class Analyses (LCA) to examine subjective responses to two categories of drugs and link these to abuse and dependence. In 1992, subjective responses were queried of 2506 marijuana and 661 cocaine lifetime users who were members of the Vietnam Era Twin Registry. LCA was used to identify classes of subjective effects. Multinomial logistic regression models were computed to test for an association between classes and marijuana and cocaine abuse or dependence. The best LCA solution for marijuana identified 6 distinct classes characterized as positive, relaxed, reactive, adverse, low and very reactive. The best LCA solution for cocaine identified 5 distinct classes characterized as positive, alert, adverse, low and very reactive. Marijuana abuse and dependence were significantly associated with each latent class. Cocaine abuse was associated with the reactive class (OR=3.9; 95% CI: 1.6-9.5). Cocaine dependence was associated with reactive (OR=15.3; 95% CI: 7.1-32.6), adverse (OR=9.7; 95% CI: 4.5-21.0) and very reactive (OR=18.7; 95% CI: 5.6-62.6) classes. We found evidence for both qualitative and quantitative subjective effect profiles. Subjective effects, both positive and adverse are associated with lifetime risk for marijuana and cocaine dependence.

The marine bacterium Marinobacter hydrocarbonoclasticus SP17 degrades a wide range of lipids and hydrocarbons through the formation of oleolytic biofilms with distinct gene expression profiles.

PubMed

Mounier, Julie; Camus, Arantxa; Mitteau, Isabelle; Vaysse, Pierre-Joseph; Goulas, Philippe; Grimaud, Régis; Sivadon, Pierre

2014-12-01

Hydrophobic organic compounds (mainly lipids and hydrocarbons) represent a significant part of the organic matter in marine waters, and their degradation has an important impact in the carbon fluxes within oceans. However, because they are nearly insoluble in the water phase, their degradation by microorganisms occurs at the interface with water and thus requires specific adaptations such as biofilm formation. We show that Marinobacter hydrocarbonoclasticus SP17 develops biofilms, referred to as oleolytic biofilms, on a large variety of hydrophobic substrates, including hydrocarbons, fatty alcohols, fatty acids, triglycerides, and wax esters. Microarray analysis revealed that biofilm growth on n-hexadecane or triolein involved distinct genetic responses, together with a core of common genes that might concern general mechanisms of biofilm formation. Biofilm growth on triolein modulated the expression of hundreds of genes in comparison with n-hexadecane. The processes related to primary metabolism and genetic information processing were downregulated. Most of the genes that were overexpressed on triolein had unknown functions. Surprisingly, their genome localization was restricted to a few regions identified as putative genomic islands or mobile elements. These results are discussed with regard to the adaptive responses triggered by M. hydrocarbonoclasticus SP17 to occupy a specific niche in marine ecosystems. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Gold nanocluster-based ratiometric fluorescent probes for hydrogen peroxide and enzymatic sensing of uric acid.

PubMed

Yang, Dongqin; Luo, Minchuan; Di, Junwei; Tu, Yifeng; Yan, Jilin

2018-05-18

A method is described for ratiometric fluorometric assays of H 2 O 2  by using two probes that have distinct response profiles. Under the catalytic action of ferrous ion, the 615 nm emission of protein-stabilized gold nanoclusters (under 365 nm photoexcitation) is quenched by H 2 O 2 , while an increased signal is generated with a peak at 450 nm by oxidizing coumarin with the H 2 O 2 /Fe(II) system to form a blue emitting fluorophore. These decrease/increase responses give a ratiometric signal. The ratio of the fluorescences at the two peaks are linearly related to the concentration of H 2 O 2 in the range from 0.05 to 10 μM, with a 7.7 nM limit of detection. The detection scheme was further coupled to the urate oxidase catalyzed oxidation of uric acid which proceeds under the formation of H 2 O 2 . This method provides an simple and effective means for the construction of ratiometric fluorometric (enzymatic) assays that involve the detection of H 2 O 2 . Graphical abstract Under catalysis by ferrous ion, hydrogen peroxide quenches the luminescence of gold nanoclusters (AuNCs) and oxidizes coumarin into a fluorescent derivative, which rendered fluorescence ON and OFF at two distinct wavelengths for ratiometric measurements.

Distinct transcriptome profiles identified in normal human bronchial epithelial cells after exposure to γ-rays and different elemental particles of high Z and energy.

PubMed

Ding, Liang-Hao; Park, Seongmi; Peyton, Michael; Girard, Luc; Xie, Yang; Minna, John D; Story, Michael D

2013-06-01

Ionizing radiation composed of accelerated ions of high atomic number (Z) and energy (HZE) deposits energy and creates damage in cells in a discrete manner as compared to the random deposition of energy and damage seen with low energy radiations such as γ- or x-rays. Such radiations can be highly effective at cell killing, transformation, and oncogenesis, all of which are concerns for the manned space program and for the burgeoning field of HZE particle radiotherapy for cancer. Furthermore, there are differences in the extent to which cells or tissues respond to such exposures that may be unrelated to absorbed dose. Therefore, we asked whether the energy deposition patterns produced by different radiation types would cause different molecular responses. We performed transcriptome profiling using human bronchial epithelial cells (HBECs) after exposure to γ-rays and to two different HZE particles (28Si and 56Fe) with different energy transfer properties to characterize the molecular response to HZE particles and γ-rays as a function of dose, energy deposition pattern, and time post-irradiation. Clonogenic assay indicated that the relative biological effectiveness (RBE) for 56Fe was 3.91 and for 28Si was 1.38 at 34% cell survival. Unsupervised clustering analysis of gene expression segregated samples according to the radiation species followed by the time after irradiation, whereas dose was not a significant parameter for segregation of radiation response. While a subset of genes associated with p53-signaling, such as CDKN1A, TRIM22 and BTG2 showed very similar responses to all radiation qualities, distinct expression changes were associated with the different radiation species. Gene enrichment analysis categorized the differentially expressed genes into functional groups related to cell death and cell cycle regulation for all radiation types, while gene pathway analysis revealed that the pro-inflammatory Acute Phase Response Signaling was specifically induced after HZE particle irradiation. A 73 gene signature capable of predicting with 96% accuracy the radiation species to which cells were exposed, was developed. These data suggest that the molecular response to the radiation species used here is a function of the energy deposition characteristics of the radiation species. This novel molecular response to HZE particles may have implications for radiotherapy including particle selection for therapy and risk for second cancers, risk for cancers from diagnostic radiation exposures, as well as NASA's efforts to develop more accurate lung cancer risk estimates for astronaut safety. Lastly, irrespective of the source of radiation, the gene expression changes observed set the stage for functional studies of initiation or progression of radiation-induced lung carcinogenesis.

Distinct transcriptome profiles identified in normal human bronchial epithelial cells after exposure to γ-rays and different elemental particles of high Z and energy

PubMed Central

2013-01-01

Background Ionizing radiation composed of accelerated ions of high atomic number (Z) and energy (HZE) deposits energy and creates damage in cells in a discrete manner as compared to the random deposition of energy and damage seen with low energy radiations such as γ- or x-rays. Such radiations can be highly effective at cell killing, transformation, and oncogenesis, all of which are concerns for the manned space program and for the burgeoning field of HZE particle radiotherapy for cancer. Furthermore, there are differences in the extent to which cells or tissues respond to such exposures that may be unrelated to absorbed dose. Therefore, we asked whether the energy deposition patterns produced by different radiation types would cause different molecular responses. We performed transcriptome profiling using human bronchial epithelial cells (HBECs) after exposure to γ-rays and to two different HZE particles (28Si and 56Fe) with different energy transfer properties to characterize the molecular response to HZE particles and γ-rays as a function of dose, energy deposition pattern, and time post-irradiation. Results Clonogenic assay indicated that the relative biological effectiveness (RBE) for 56Fe was 3.91 and for 28Si was 1.38 at 34% cell survival. Unsupervised clustering analysis of gene expression segregated samples according to the radiation species followed by the time after irradiation, whereas dose was not a significant parameter for segregation of radiation response. While a subset of genes associated with p53-signaling, such as CDKN1A, TRIM22 and BTG2 showed very similar responses to all radiation qualities, distinct expression changes were associated with the different radiation species. Gene enrichment analysis categorized the differentially expressed genes into functional groups related to cell death and cell cycle regulation for all radiation types, while gene pathway analysis revealed that the pro-inflammatory Acute Phase Response Signaling was specifically induced after HZE particle irradiation. A 73 gene signature capable of predicting with 96% accuracy the radiation species to which cells were exposed, was developed. Conclusions These data suggest that the molecular response to the radiation species used here is a function of the energy deposition characteristics of the radiation species. This novel molecular response to HZE particles may have implications for radiotherapy including particle selection for therapy and risk for second cancers, risk for cancers from diagnostic radiation exposures, as well as NASA’s efforts to develop more accurate lung cancer risk estimates for astronaut safety. Lastly, irrespective of the source of radiation, the gene expression changes observed set the stage for functional studies of initiation or progression of radiation-induced lung carcinogenesis. PMID:23724988

Vertical electromagnetic profiling (VEMP)

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

Lytle, R.J.

1984-08-01

Vertical seismic profiling (VSP) is based upon reception measurements performed in a borehole with a source near the ground surface. This technology has seen a surge in application and development in the last decade. The analogous concept of vertical electromagnetic profiling (VEMP) consists of reception measurements performed in a borehole with a source near the ground surface. Although the electromagnetic concept has seen some application, this technology has not been as systematically developed and applied as VSP. Vertical electromagnetic profiling provides distinct and complementary data due to sensing different physical parameters than seismic profiling. Certain of the advantages of VEMPmore » are presented. 28 references, 7 figures.« less

RASopathies are associated with a distinct personality profile.

PubMed

Bizaoui, Varoona; Gage, Jessica; Brar, Rita; Rauen, Katherine A; Weiss, Lauren A

2018-06-01

Personality is a complex, yet partially heritable, trait. Although some Mendelian diseases like Williams-Beuren syndrome are associated with a particular personality profile, studies have failed to assign the personality features to a single gene or pathway. As a family of monogenic disorders caused by mutations in the Ras/MAPK pathway known to influence social behavior, RASopathies are likely to provide insight into the genetic basis of personality. Eighty subjects diagnosed with cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis type 1, and Noonan syndrome were assessed using a parent-report BFQ-C (Big Five Questionnaire for Children) evaluating agreeableness, extraversion, conscientiousness, intellect/openness, and neuroticism, along with 55 unaffected sibling controls. A short questionnaire was added to assess sense of humor. RASopathy subjects and sibling controls were compared for individual components of personality, multidimensional personality profiles, and individual questions using Student tests, analysis of variance, and principal component analysis. RASopathy subjects were given lower scores on average compared to sibling controls in agreeableness, extraversion, conscientiousness, openness, and sense of humor, and similar scores in neuroticism. When comparing the multidimensional personality profile between groups, RASopathies showed a distinct profile from unaffected siblings, but no difference in this global profile was found within RASopathies, revealing a common profile for the Ras/MAPK-related disorders. In addition, several syndrome-specific strengths or weaknesses were observed in individual domains. We describe for the first time an association between a single pathway and a specific personality profile, providing a better understanding of the genetics underlying personality, and new tools for tailoring educational and behavioral approaches for individuals with RASopathies. © 2018 Wiley Periodicals, Inc.

Perceived autonomy support, psychological needs satisfaction, depressive symptoms and apathy in French hospitalized older people.

PubMed

Souesme, Guillaume; Martinent, Guillaume; Ferrand, Claude

2016-01-01

Based on the self-determination theory, the aim of the present study was (1) to provide a better understanding of older people's psychological needs satisfaction in geriatric care units, then to link this information with depressive symptoms and apathy; (2) to examine whether the perceived autonomy support from health care professionals differs between needs satisfaction profiles; and (3) to investigate for all participants how each need satisfaction was related to depressive symptoms and apathy. Participants (N=100; Mage=83.33years, SD=7.78, 61% female) completed the measures of psychological needs satisfaction, perceived autonomy support, geriatric depression and apathy. Sociodemographic data were also collected. Cluster analyses showed three distinct profiles: one profile with low-moderate need satisfaction, one profile with high-moderate need satisfaction and one profile with high need satisfaction. These profiles are distinct, and did not differ in terms of participants' characteristics, except gender. Multivariate analysis of covariance (MANCOVA) revealed that participants with low-moderate need satisfaction profile have significantly higher level of depressive symptoms and apathy, and lower levels of perceived autonomy support than participants of the two other profiles. Moreover, for all participants, regression analyses revealed that both competence and relatedness needs satisfaction significantly and negatively explained 28% of the variance in depressive symptoms score and 44% of the variance in apathy score. Our results highlight the interest to examine more thoroughly the variables fostering autonomy-supportive environment in geriatric care units, and to deepen the relationship between competence and relatedness needs satisfaction and depressive symptoms and apathy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Different protein profile in amniotic fluid with nervous system malformations by surface-enhanced laser desorption-ionization/time-of-flight mass spectrometry (SELDI-TOF-MS) technology.

PubMed

Ma, Zhe; Liu, Cun; Deng, Biping; Dong, Shaogang; Tao, Guowei; Zhan, Xinfeng; Wang, Chuner; Liu, Shaoping; Qu, Xun

2010-12-01

To detect the distinct proteins in amniotic fluid (AF) between nervous system malformations fetuses and normal fetuses. Surface-enhanced laser desorption-ionization/time-of-flight mass spectrometry was used to characterize AF peptides in AF between nervous system malformations fetuses and normal fetuses. WCX2 protein chips were used to characterize AF peptides in AF. Protein chips were examined in a PBSIIC protein reader, the protein profiling was collected by ProteinChip software version 3.1 (Ciphergen Biosystems, Fremont, CA, USA) and analyzed by Biomarker Wizard software (Ciphergen Biosystems). Nine distinct proteins were identified in AF between nervous system malformations fetuses and normal fetuses. Compared with the control group, three proteins with m/z 4967.5 Da, 5258.0 Da, and 11,717.0 Da were down-regulated, and six proteins with m/z 2540.4 Da, 3107.1 Da, 3396.8 Da, 4590.965 Da, 5589.2 Da and 6429.4 Da up-regulated in nervous system malformations fetuses. The results suggest that there are distinct proteins in protein profiling of AF between nervous system malformations fetuses and normal fetuses. © 2010 The Authors. Journal of Obstetrics and Gynaecology Research © 2010 Japan Society of Obstetrics and Gynecology.

Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma

NASA Astrophysics Data System (ADS)

Jalbert, Llewellyn E.; Elkhaled, Adam; Phillips, Joanna J.; Neill, Evan; Williams, Aurelia; Crane, Jason C.; Olson, Marram P.; Molinaro, Annette M.; Berger, Mitchel S.; Kurhanewicz, John; Ronen, Sabrina M.; Chang, Susan M.; Nelson, Sarah J.

2017-03-01

Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy.

A Phenotype Classification of Internet Use Disorder in a Large-Scale High-School Study.

PubMed

Lindenberg, Katajun; Halasy, Katharina; Szász-Janocha, Carolin; Wartberg, Lutz

2018-04-12

Internet Use Disorder (IUD) affects numerous adolescents worldwide, and (Internet) Gaming Disorder, a specific subtype of IUD, has recently been included in DSM-5 and ICD-11. Epidemiological studies have identified prevalence rates up to 5.7% among adolescents in Germany. However, little is known about the risk development during adolescence and its association to education. The aim of this study was to: (a) identify a clinically relevant latent profile in a large-scale high-school sample; (b) estimate prevalence rates of IUD for distinct age groups and (c) investigate associations to gender and education. N = 5387 adolescents out of 41 schools in Germany aged 11-21 were assessed using the Compulsive Internet Use Scale (CIUS). Latent profile analyses showed five profile groups with differences in CIUS response pattern, age and school type. IUD was found in 6.1% and high-risk Internet use in 13.9% of the total sample. Two peaks were found in prevalence rates indicating the highest risk of IUD in age groups 15-16 and 19-21. Prevalence did not differ significantly between boys and girls. High-level education schools showed the lowest (4.9%) and vocational secondary schools the highest prevalence rate (7.8%). The differences between school types could not be explained by academic level.

Heterogeneity of executive functions among comorbid neurodevelopmental disorders

PubMed Central

Dajani, Dina R.; Llabre, Maria M.; Nebel, Mary Beth; Mostofsky, Stewart H.; Uddin, Lucina Q.

2016-01-01

Executive functions (EFs) are used to set goals, plan for the future, inhibit maladaptive responses, and change behavior flexibly. Although some studies point to specific EF profiles in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) — prevalent and often highly comorbid neurodevelopmental disorders — others have not differentiated them. The objective of the current study was to identify distinct profiles of EF across typically developing (TD) children and children with ASD and ADHD. We employed a latent profile analysis using indicators of EF (e.g., working memory, inhibition, and flexibility) in a mixed group of 8–13 year-olds including TD children (n = 128), children with ASD without ADHD (n = 30), children with ADHD (n = 93), and children with comorbid ASD and ADHD (n = 66). Three EF classes emerged: “above average,” “average,” and “impaired.” EF classes did not reproduce diagnostic categories, suggesting that differences in EF abilities are present within the ASD and ADHD groups. Further, greater EF dysfunction predicted more severe socioemotional problems, such as anxiety/depression. These results highlight the heterogeneity of current diagnostic groups and identify an “impaired” EF group, consisting of children with both ASD and ADHD, which could specifically be targeted for EF intervention. PMID:27827406

Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression.

PubMed

Pescatori, Mario; Broccolini, Aldobrando; Minetti, Carlo; Bertini, Enrico; Bruno, Claudio; D'amico, Adele; Bernardini, Camilla; Mirabella, Massimiliano; Silvestri, Gabriella; Giglio, Vincenzo; Modoni, Anna; Pedemonte, Marina; Tasca, Giorgio; Galluzzi, Giuliana; Mercuri, Eugenio; Tonali, Pietro A; Ricci, Enzo

2007-04-01

Genome-wide gene expression profiling of skeletal muscle from Duchenne muscular dystrophy (DMD) patients has been used to describe muscle tissue alterations in DMD children older than 5 years. By studying the expression profile of 19 patients younger than 2 years, we describe with high resolution the gene expression signature that characterizes DMD muscle during the initial or "presymptomatic" phase of the disease. We show that in the first 2 years of the disease, DMD muscle is already set to express a distinctive gene expression pattern considerably different from the one expressed by normal, age-matched muscle. This "dystrophic" molecular signature is characterized by a coordinate induction of genes involved in the inflammatory response, extracellular matrix (ECM) remodeling and muscle regeneration, and the reduced transcription of those involved in energy metabolism. Despite the lower degree of muscle dysfunction experienced, our younger patients showed abnormal expression of most of the genes reported as differentially expressed in more advanced stages of the disease. By analyzing our patients as a time series, we provide evidence that some genes, including members of three pathways involved in morphogenetic signaling-Wnt, Notch, and BMP-are progressively induced or repressed in the natural history of DMD.

Transcription profile of brewery yeast under fermentation conditions.

PubMed

James, T C; Campbell, S; Donnelly, D; Bond, U

2003-01-01

Yeast strains, used in the brewing industry, experience distinctive physiological conditions. During a brewing fermentation, yeast are exposed to anaerobic conditions, high pressure, high specific gravity and low temperatures. The purpose of this study was to examine the global gene expression profile of yeast subjected to brewing stress. We have carried out a microarray analysis of a typical brewer's yeast during the course of an 8-day fermentation in 15 degrees P wort. We used the probes derived from Saccharomyces cerevisiae genomic DNA on the chip and RNA isolated from three stages of brewing. This analysis shows a high level of expression of genes involved in fatty acid and ergosterol biosynthesis early in fermentation. Furthermore, genes involved in respiration and mitochondrial protein synthesis also show higher levels of expression. Surprisingly, we observed a complete repression of many stress response genes and genes involved in protein synthesis throughout the 8-day period compared with that at the start of fermentation. This microarray data set provides an analysis of gene expression under brewing fermentation conditions. The data provide an insight into the various metabolic processes altered or activated by brewing conditions of growth. This study leads to future experiments whereby selective alterations in brewing conditions could be introduced to take advantage of the changing transcript profile to improve the quality of the brew.

Extracting the normal lung dose-response curve from clinical DVH data: a possible role for low dose hyper-radiosensitivity, increased radioresistance

NASA Astrophysics Data System (ADS)

Gordon, J. J.; Snyder, K.; Zhong, H.; Barton, K.; Sun, Z.; Chetty, I. J.; Matuszak, M.; Ten Haken, R. K.

2015-09-01

In conventionally fractionated radiation therapy for lung cancer, radiation pneumonitis’ (RP) dependence on the normal lung dose-volume histogram (DVH) is not well understood. Complication models alternatively make RP a function of a summary statistic, such as mean lung dose (MLD). This work searches over damage profiles, which quantify sub-volume damage as a function of dose. Profiles that achieve best RP predictive accuracy on a clinical dataset are hypothesized to approximate DVH dependence. Step function damage rate profiles R(D) are generated, having discrete steps at several dose points. A range of profiles is sampled by varying the step heights and dose point locations. Normal lung damage is the integral of R(D) with the cumulative DVH. Each profile is used in conjunction with a damage cutoff to predict grade 2 plus (G2+) RP for DVHs from a University of Michigan clinical trial dataset consisting of 89 CFRT patients, of which 17 were diagnosed with G2+ RP. Optimal profiles achieve a modest increase in predictive accuracy—erroneous RP predictions are reduced from 11 (using MLD) to 8. A novel result is that optimal profiles have a similar distinctive shape: enhanced damage contribution from low doses (<20 Gy), a flat contribution from doses in the range ~20-40 Gy, then a further enhanced contribution from doses above 40 Gy. These features resemble the hyper-radiosensitivity / increased radioresistance (HRS/IRR) observed in some cell survival curves, which can be modeled using Joiner’s induced repair model. A novel search strategy is employed, which has the potential to estimate RP dependence on the normal lung DVH. When applied to a clinical dataset, identified profiles share a characteristic shape, which resembles HRS/IRR. This suggests that normal lung may have enhanced sensitivity to low doses, and that this sensitivity can affect RP risk.

Variations in Decision-Making Profiles by Age and Gender: A Cluster-Analytic Approach.

PubMed

Delaney, Rebecca; Strough, JoNell; Parker, Andrew M; de Bruin, Wandi Bruine

2015-10-01

Using cluster-analysis, we investigated whether rational, intuitive, spontaneous, dependent, and avoidant styles of decision making (Scott & Bruce, 1995) combined to form distinct decision-making profiles that differed by age and gender. Self-report survey data were collected from 1,075 members of RAND's American Life Panel (56.2% female, 18-93 years, M age = 53.49). Three decision-making profiles were identified: affective/experiential, independent/self-controlled, and an interpersonally-oriented dependent profile. Older people were less likely to be in the affective/experiential profile and more likely to be in the independent/self-controlled profile. Women were less likely to be in the affective/experiential profile and more likely to be in the interpersonally-oriented dependent profile. Interpersonally-oriented profiles are discussed as an overlooked but important dimension of how people make important decisions.

Different behavioral effect dose–response profiles in mice exposed to two-carbon chlorinated hydrocarbons: Influence of structural and physical properties

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

Umezu, Toyoshi, E-mail: umechan2@nies.go.jp; Shibata, Yasuyuki, E-mail: yshibata@nies.go.jp

2014-09-01

The present study aimed to clarify whether dose–response profiles of acute behavioral effects of 1,2-dichloroethane (DCE), 1,1,1-trichloroethane (TCE), trichloroethylene (TRIC), and tetrachloroethylene (PERC) differ. A test battery involving 6 behavioral endpoints was applied to evaluate the effects of DCE, TCE, TRIC, and PERC in male ICR strain mice under the same experimental conditions. The behavioral effect dose–response profiles of these compounds differed. Regression analysis was used to evaluate the relationship between the dose–response profiles and structural and physical properties of the compounds. Dose–response profile differences correlated significantly with differences in specific structural and physical properties. These results suggest that differencesmore » in specific structural and physical properties of DCE, TCE, TRIC, and PERC are responsible for differences in behavioral effects that lead to a variety of dose–response profiles. - Highlights: • We examine effects of 4 chlorinated hydrocarbons on 6 behavioral endpoints in mice. • The behavioral effect dose–response profiles for the 4 compounds are different. • We utilize regression analysis to clarify probable causes of the different profiles. • The compound's physicochemical properties probably produce the different profiles.« less

Genetic structure of Eurasian and North American Leymus (Triticeae) wildryes assessed by chloroplast DNA sequences and AFLP profiles

Treesearch

C. Mae Culumber; Steve R. Larson; Kevin B. Jensen; Thomas A. Jones

2011-01-01

Leymus is a genomically defined allopolyploid of genus Triticeae with two distinct subgenomes. Chloroplast DNA sequences of Eurasian and North American species are distinct and polyphyletic. However, phylogenies derived from chloroplast and nuclear DNA sequences are confounded by polyploidy and lack of polymorphism among many taxa. The AFLP technique can resolve...

Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease.

PubMed

Jurynczyk, Maciej; Probert, Fay; Yeo, Tianrong; Tackley, George; Claridge, Tim D W; Cavey, Ana; Woodhall, Mark R; Arora, Siddharth; Winkler, Torsten; Schiffer, Eric; Vincent, Angela; DeLuca, Gabriele; Sibson, Nicola R; Isabel Leite, M; Waters, Patrick; Anthony, Daniel C; Palace, Jacqueline

2017-12-06

The overlapping clinical features of relapsing remitting multiple sclerosis (RRMS), aquaporin-4 (AQP4)-antibody (Ab) neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease mean that detection of disease specific serum antibodies is the gold standard in diagnostics. However, antibody levels are not prognostic and may become undetectable after treatment or during remission. Therefore, there is still a need to discover antibody-independent biomarkers. We sought to discover whether plasma metabolic profiling could provide biomarkers of these three diseases and explore if the metabolic differences are independent of antibody titre. Plasma samples from 108 patients (34 RRMS, 54 AQP4-Ab NMOSD, and 20 MOG-Ab disease) were analysed by nuclear magnetic resonance spectroscopy followed by lipoprotein profiling. Orthogonal partial-least squares discriminatory analysis (OPLS-DA) was used to identify significant differences in the plasma metabolite concentrations and produce models (mathematical algorithms) capable of identifying these diseases. In all instances, the models were highly discriminatory, with a distinct metabolite pattern identified for each disease. In addition, OPLS-DA identified AQP4-Ab NMOSD patient samples with low/undetectable antibody levels with an accuracy of 92%. The AQP4-Ab NMOSD metabolic profile was characterised by decreased levels of scyllo-inositol and small high density lipoprotein particles along with an increase in large low density lipoprotein particles relative to both RRMS and MOG-Ab disease. RRMS plasma exhibited increased histidine and glucose, along with decreased lactate, alanine, and large high density lipoproteins while MOG-Ab disease plasma was defined by increases in formate and leucine coupled with decreased myo-inositol. Despite overlap in clinical measures in these three diseases, the distinct plasma metabolic patterns support their distinct serological profiles and confirm that these conditions are indeed different at a molecular level. The metabolites identified provide a molecular signature of each condition which is independent of antibody titre and EDSS, with potential use for disease monitoring and diagnosis.

Framework for community functioning: synthesis of stress gradient and resource partitioning concepts

PubMed Central

2017-01-01

To understand how communities function and generate abundance, I develop a framework integrating elements from the stress gradient and resource partitioning concepts. The framework suggests that guild abundance depends on environmental and spatial factors but also on inter-guild interactions (competitor or facilitator richness), which can alter the fundamental niche of constituent species in negative (competition) or positive direction (facilitation). Consequently, the environmental and spatial mechanisms driving guild abundance would differ across guilds and interaction modes. Using continental data on stream diatoms and physico-chemistry, the roles of these mechanisms were tested under three interaction modes—shared preference, distinct preference, and facilitative, whereby pairs of guilds exhibited, respectively, a dominance-tolerance tradeoff along a eutrophication gradient, specialization along a pH gradient, or a donor-recipient relationship along a nitrogen gradient. Representative of the shared preference mode were the motile (dominant) and low profile (tolerant) guilds, of the distinct preference mode—the acidophilous and alkaliphilous (low profile) guilds, and of the facilitative mode—nitrogen fixers (donors) and motile species (recipients). In each mode, the influences of environment, space (latitude and longitude), and competitor or facilitator richness on guild density were assessed by variance partitioning. Pure environment constrained most strongly the density of the dominant, the acidophilous, and the recipient guild in the shared preference, distinct preference, and facilitative mode, respectively, while spatial effects were important only for the low profile guild. Higher competitor richness was associated with lower density of the tolerant guild in the shared preference mode, both guilds in the distinct preference mode, and the donor guild in the facilitative mode. Conversely, recipient density in the facilitative mode increased with donor richness in stressful nitrogen-poor environments. Thus, diatom guild abundance patterns were determined primarily by biotic and/or environmental impacts and, with the exception of the low profile guild, were insensitive to spatial effects. This framework identifies major sources of variability in diatom guild abundance with implications for the understanding of biodiversity-ecosystem functioning. PMID:29018618

Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila

PubMed Central

Katzenberger, Rebeccah J.; Ganetzky, Barry; Wassarman, David A.

2016-01-01

Outcomes of traumatic brain injury (TBI) vary because of differences in primary and secondary injuries. Primary injuries occur at the time of a traumatic event, whereas secondary injuries occur later as a result of cellular and molecular events activated in the brain and other tissues by primary injuries. We used a Drosophila melanogaster TBI model to investigate secondary injuries that cause acute mortality. By analyzing mortality percentage within 24 hr of primary injuries, we previously found that age at the time of primary injuries and diet afterward affect the severity of secondary injuries. Here, we show that secondary injuries peaked in activity 1–8 hr after primary injuries. Additionally, we demonstrate that age and diet activated distinct secondary injuries in a genotype-specific manner, and that concurrent activation of age- and diet-regulated secondary injuries synergistically increased mortality. To identify genes involved in secondary injuries that cause mortality, we compared genome-wide mRNA expression profiles of uninjured and injured flies under age and diet conditions that had different mortalities. During the peak period of secondary injuries, innate immune response genes were the predominant class of genes that changed expression. Furthermore, age and diet affected the magnitude of the change in expression of some innate immune response genes, suggesting roles for these genes in inhibiting secondary injuries that cause mortality. Our results indicate that the complexity of TBI outcomes is due in part to distinct, genetically controlled, age- and diet-regulated mechanisms that promote secondary injuries and that involve a subset of innate immune response genes. PMID:27754853

Volatile profile of aromatic and non-aromatic rice cultivars using SPME/GC-MS

USDA-ARS?s Scientific Manuscript database

Rice (Oryza sativa L.) is enjoyed by many people as a staple food because of its flavor and texture. Some cultivars, like scented rice, are preferred over others due to their distinctive aroma and flavor. The volatile profile of rice has been explored by many investigators, some of whom have also ...

Volatile profile of aromatic and non-aromatic rice cultivars using SPME/GC-MS

USDA-ARS?s Scientific Manuscript database

Rice (Oryza sativa L.) is enjoyed by many people as a staple food because of its flavor and texture. Some cultivars, like scented rice, are preferred over others due to their distinctive aroma and flavor. The volatile profile of rice has been explored by many investigators, some of whom have deter...

Profiles of Personal Resiliency in Youth Who Have Experienced Physical or Sexual Abuse

ERIC Educational Resources Information Center

Deblinger, Esther; Runyon, Melissa K.; Steer, Robert A.

2014-01-01

To determine whether children and adolescents (7-17 years old) who had experienced physical, sexual, or both types of abuse reflected distinct profiles of personal resiliency, we administered the "Resiliency Scales for Children and Adolescents" (RSCA) to 250 youth. We performed cluster analyses with T scores for the RSCA Self-Mastery,…

Profiles of Personal Resiliency in Child and Adolescent Psychiatric Inpatients

ERIC Educational Resources Information Center

Kumar, Geetha; Steer, Robert A.; Gulab, Nazli A.

2010-01-01

To ascertain whether children and adolescents whose ages ranged from 9 to 17 years described distinct profiles of personal resiliency, the Resiliency Scales for Children and Adolescents (RSCA) were administered to 100 youth who were admitted to an inpatient psychiatric unit and were diagnosed with various "DSM-IV-TR" disorders along with the Beck…

Working Memory Differences between Children Living in Rural and Urban Poverty

ERIC Educational Resources Information Center

Tine, Michele

2014-01-01

This study was designed to investigate if the working memory profiles of children living in rural poverty are distinct from the working memory profiles of children living in urban poverty. Verbal and visuospatial working memory tasks were administered to sixth-grade students living in low-income rural, low-income urban, high-income rural, and…

Investigation of Profiles of Risk Factors for Adolescent Psychopathology: A Person-Centered Approach

ERIC Educational Resources Information Center

Parra, Gilbert R.; DuBois, David L.; Sher, Kenneth J.

2006-01-01

Latent variable mixture modeling was used to identify subgroups of adolescents with distinct profiles of risk factors from individual, family, peer, and broader contextual domains. Data were drawn from the National Longitudinal Study of Adolescent Health. Four-class models provided the most theoretically meaningful solutions for both 7th (n = 907;…

From inflammation to wound healing: using a simple model to understand the functional versatility of murine macrophages.

PubMed

Childs, Lauren M; Paskow, Michael; Morris, Sidney M; Hesse, Matthias; Strogatz, Steven

2011-11-01

Macrophages are fundamental cells of the innate immune system. Their activation is essential for such distinct immune functions as inflammation (pathogen-killing) and tissue repair (wound healing). An open question has been the functional stability of an individual macrophage cell: whether it can change its functional profile between different immune responses such as between the repair pathway and the inflammatory pathway. We studied this question theoretically by constructing a rate equation model for the key substrate, enzymes and products of the pathways; we then tested the model experimentally. Both our model and experiments show that individual macrophages can switch from the repair pathway to the inflammation pathway but that the reverse switch does not occur.

From Inflammation to Wound Healing: Using a Simple Model to Understand the Functional Versatility of Murine Macrophages

PubMed Central

Paskow, Michael; Morris, Sidney M.; Hesse, Matthias; Strogatz, Steven

2011-01-01

Macrophages are fundamental cells of the innate immune system. Their activation is essential for such distinct immune functions as inflammation (pathogen-killing) and tissue repair (wound healing). An open question has been the functional stability of an individual macrophage cell: whether it can change its functional profile between different immune responses such as between the repair pathway and the inflammatory pathway. We studied this question theoretically by constructing a rate equation model for the key substrate, enzymes and products of the pathways; we then tested the model experimentally. Both our model and experiments show that individual macrophages can switch from the repair pathway to the inflammation pathway but that the reverse switch does not occur. PMID:21347813

Role of epigenetic modifications in luminal breast cancer

PubMed Central

Abdel-Hafiz, Hany A; Horwitz, Kathryn B

2015-01-01

Luminal breast cancers represent approximately 75% of cases. Explanations into the causes of endocrine resistance are complex and are generally ascribed to genomic mechanisms. Recently, attention has been drawn to the role of epigenetic modifications in hormone resistance. We review these here. Epigenetic modifications are reversible, heritable and include changes in DNA methylation patterns, modification of histones and altered microRNA expression levels that target the receptors or their signaling pathways. Large-scale analyses indicate distinct epigenomic profiles that distinguish breast cancers from normal and benign tissues. Taking advantage of the reversibility of epigenetic modifications, drugs that target epigenetic modifiers, given in combination with chemotherapies or endocrine therapies, may represent promising approaches to restoration of therapy responsiveness in these cases. PMID:25689414

A distinct profile of serum levels of soluble intercellular adhesion molecule-1 and intercellular adhesion molecule-3 in mycosis fungoides and Sézary syndrome.

PubMed

López-Lerma, Ingrid; Estrach, Maria Teresa

2009-08-01

Cell adhesion molecules (CAMs) play a pivotal role in cutaneous localization of T cells. Tissue-selective localization of T lymphocytes to the skin is crucial for immune surveillance and in the pathogenesis of skin disorders. To detect the profile of soluble CAMs in patients with cutaneous T-cell lymphoma (CTCL), we investigated the levels of intercellular adhesion molecule-1 (ICAM-1, soluble ICAM-1 [sICAM-1]); intercellular adhesion molecule-3 (sICAM-3); vascular cell adhesion molecule-1 (sVCAM-1); and E-selectin (sE-selectin) in sera from patients with T-cell-mediated skin diseases. Serum levels of the 4 CAMs were measured by enzyme-linked immunosorbent assay in 42 participants including 11 patients with early stages of CTCL; 7 with advanced stages of CTCL including Sézary syndrome; 12 with inflammatory skin diseases (psoriasis and atopic dermatitis); 8 with skin diseases that may evolve into CTCL; and healthy individuals. Levels were correlated with biological parameters known as prognostic factors in non-Hodgkin lymphomas. In patients with CTCL, significantly increased levels of sICAM-1 and sICAM-3 were found when compared with healthy individuals and patients with inflammatory dermatosis. Soluble E-selectin and sVCAM-1 levels were not increased. There were significant positive correlations between sICAM-1 and sICAM-3 levels and each of them with beta2-microglobulin levels. Limited number of patients was a limitation. There is a distinct profile of soluble CAMs in patients with CTCL. However, future studies with a larger group of patients are needed to confirm these findings. We propose that high sICAM-1 and sICAM-3 levels have important implications in the context of immune response and immune surveillance in these patients.

Sensory representation of typicality of Cabernet franc wines related to phenolic composition: impact of ripening stage and maceration time.

PubMed

Cadot, Yves; Caillé, Soline; Samson, Alain; Barbeau, Gérard; Cheynier, Véronique

2012-06-30

Phenolics are responsible for important sensory properties of red wines, including colour, astringency, and possibly bitterness. From a technical viewpoint, the harvest date and the maceration duration are critical decisions for producing red wine with a distinctive style. But little is known about the evolution of phenolics and of their extractability during ripening to predict the composition of the wine and related sensory properties. The aim of this study was to understand the relationship between the sensory profile of the wines and (i) the ripening stage of the berries (harvest date) and (ii) the extraction time (maceration duration). Phenolic acids, flavonols, anthocyanins and proanthocyanidins of Vitis Vinifera var. Cabernet franc were measured in grapes and in wines from two stages of maturity and with two maceration durations. Phenolic composition was analysed by high performance liquid chromatography, after fractionation and thiolysis for proanthocyanidins. The distinctive style of wines was investigated by descriptive analysis (trained panel), Just About Right profiles and typicality assessment (wine expert panel). Relationships between phenolics and sensory attributes were established by multidimensional analysis, and phenolics were classified according to sensory data by ANOVA and PLS regressions. Astringency, bitterness, colour intensity and alcohol significantly increased with ripening and astringency and colour intensity increased with maceration time. Grape anthocyanins increased and thiolysis yield significantly decreased with ripening. In wine, proanthocyanidins increased, and mean degree of polymerisation and thiolysis yield decreased with longer extraction time. The high impact of harvest date on the sensory profiles could be due to changes in anthocyanin and sugar contents, but also to an evolution of proanthocyanidins. Moreover, proanthocyanidin composition was affected by maceration time as suggested by the decrease of thiolysis yield. Our results suggest that the wine sensory quality established by the expert panel, is linked as expected to grape quality at harvest, reflected by sugar and anthocyanin contents, but also by thiolysis yield, which requires elucidation. Copyright © 2012 Elsevier B.V. All rights reserved.

Emotional reactivity: Beware its involvement in traffic accidents.

PubMed

M'bailara, Katia; Atzeni, Thierry; Contrand, Benjamin; Derguy, Cyrielle; Bouvard, Manuel-Pierre; Lagarde, Emmanuel; Galéra, Cédric

2018-04-01

Reducing risk attributable to traffic accidents is a public health challenge. Research into risk factors in the area is now moving towards identification of the psychological factors involved, particularly emotional states. The aim of this study was to evaluate the link between emotional reactivity and responsibility in road traffic accidents. We hypothesized that the more one's emotional reactivity is disturbed, the greater the likelihood of being responsible for a traffic accident. This case-control study was based on a sample of 955 drivers injured in a motor vehicle crash. Responsibility levels were determined with a standardized method adapted from the quantitative Robertson and Drummer crash responsibility instrument. Emotional reactivity was assessed with the MATHYS. Hierarchical cluster analysis discriminated four distinctive driver's emotional reactivity profiles: basic emotional reactivity (54%), mild emotional hyper-reactivity (29%), emotional hyper-reactivity (11%) and emotional hypo-reactivity (6%). Drivers who demonstrated emotional hypo-reactivity had a 2.3-fold greater risk of being responsible for a traffic accident than those with basic emotional reactivity. Drivers' responsibility in traffic accidents depends on their emotional status. The latter can change the ability of drivers, modifying their behavior and thus increasing their propensity to exhibit risk behavior and to cause traffic accidents. Copyright © 2017 Elsevier B.V. All rights reserved.

Gene expression patterns of two dominant tallgrass prairie species differ in response to warming and altered precipitation

NASA Astrophysics Data System (ADS)

Smith, Melinda D.; Hoffman, Ava M.; Avolio, Meghan L.

2016-05-01

To better understand the mechanisms underlying plant species responses to climate change, we compared transcriptional profiles of the co-dominant C4 grasses, Andropogon gerardii Vitman and Sorghastrum nutans (L.) Nash, in response to increased temperatures and more variable precipitation regimes in a long-term field experiment in native tallgrass prairie. We used microarray probing of a closely related model species (Zea mays) to assess correlations in leaf temperature (Tleaf) and leaf water potential (LWP) and abundance changes of ~10,000 transcripts in leaf tissue collected from individuals of both species. A greater number of transcripts were found to significantly change in abundance levels with Tleaf and LWP in S. nutans than in A. gerardii. S. nutans also was more responsive to short-term drought recovery than A. gerardii. Water flow regulating transcripts associated with stress avoidance (e.g., aquaporins), as well as those involved in the prevention and repair of damage (e.g., antioxidant enzymes, HSPs), were uniquely more abundant in response to increasing Tleaf in S. nutans. The differential transcriptomic responses of the co-dominant C4 grasses suggest that these species may cope with and respond to temperature and water stress at the molecular level in distinct ways, with implications for tallgrass prairie ecosystem function.

Language and affective facial expression in children with perinatal stroke.

PubMed

Lai, Philip T; Reilly, Judy S

2015-08-01

Children with perinatal stroke (PS) provide a unique opportunity to understand developing brain-behavior relations. Previous research has noted distinctive differences in behavioral sequelae between children with PS and adults with acquired stroke: children fare better, presumably due to the plasticity of the developing brain for adaptive reorganization. Whereas we are beginning to understand language development, we know little about another communicative domain, emotional expression. The current study investigates the use and integration of language and facial expression during an interview. As anticipated, the language performance of the five and six year old PS group is comparable to their typically developing (TD) peers, however, their affective profiles are distinctive: those with right hemisphere injury are less expressive with respect to affective language and affective facial expression than either those with left hemisphere injury or TD group. The two distinctive profiles for language and emotional expression in these children suggest gradients of neuroplasticity in the developing brain. Copyright © 2015 Elsevier Inc. All rights reserved.

Transcriptome profiles link environmental variation and physiological response of Mytilus californianus between Pacific tides

PubMed Central

Place, Sean P.; Menge, Bruce A.; Hofmann, Gretchen E.

2011-01-01

Summary The marine intertidal zone is characterized by large variation in temperature, pH, dissolved oxygen and the supply of nutrients and food on seasonal and daily time scales. These oceanic fluctuations drive of ecological processes such as recruitment, competition and consumer-prey interactions largely via physiological mehcanisms. Thus, to understand coastal ecosystem dynamics and responses to climate change, it is crucial to understand these mechanisms. Here we utilize transcriptome analysis of the physiological response of the mussel Mytilus californianus at different spatial scales to gain insight into these mechanisms. We used mussels inhabiting different vertical locations within Strawberry Hill on Cape Perpetua, OR and Boiler Bay on Cape Foulweather, OR to study inter- and intra-site variation of gene expression. The results highlight two distinct gene expression signatures related to the cycling of metabolic activity and perturbations to cellular homeostasis. Intermediate spatial scales show a strong influence of oceanographic differences in food and stress environments between sites separated by ~65 km. Together, these new insights into environmental control of gene expression may allow understanding of important physiological drivers within and across populations. PMID:22563136

Social skills differences among attention-deficit/hyperactivity disorder types in a chat room assessment task.

PubMed

Mikami, Amori Yee; Huang-Pollock, Cynthia L; Pfiffner, Linda J; McBurnett, Keith; Hangai, Dana

2007-08-01

This study assessed social skills in 116 children aged 7-12 with ADHD-Combined Type (ADHD-C; n=33), ADHD-Inattentive Type (ADHD-I; n=45), and comparison children (n=38), with consideration of the role sluggish cognitive tempo (SCT) symptoms play in distinguishing profiles. Social skills were assessed using a novel computerized chat room task, in which participants were encouraged to join a conversation and type messages to interact with four computer-simulated peers. Every participant received the identical stimulus from the simulated peers, but was free to respond to it in his or her own unique way. Relative to comparison children, children with ADHD-C made off-topic and hostile responses; children with ADHD-I made off-topic responses, few responses and showed poor memory for the conversation. ADHD subtype differences remained after statistical control of IQ, reading achievement, typing skill, and comorbid disruptive behavior disorders. SCT symptoms, most prevalent among children with ADHD-I, predicted a distinct pattern of social withdrawal and lower hostility. Parent and teacher ratings and in-vivo observations of social skills correlate with this new measure.

Subgroups of Chemotherapy Patients With Distinct Morning and Evening Fatigue Trajectories

PubMed Central

Kober, Kord M.; Cooper, Bruce A.; Paul, Steven M.; Dunn, Laura B.; Levine, Jon D.; Wright, Fay; Hammer, Marilyn J.; Mastick, Judy; Venook, Alan; Aouizerat, Bradley E.; Miaskowski, Christine

2017-01-01

Purpose Purposes of this study were to: identify subgroups of patients with distinct trajectories for morning and evening fatigue; evaluate for differences in demographic and clinical characteristics among these subgroups; and compare and contrast the predictors of subgroup membership for morning and evening fatigue. Methods Outpatients with breast, gastrointestinal, gynecological, or lung cancer (n=582) completed questionnaires a total of six times over two cycles of CTX. Morning and evening fatigue severity were evaluated using the Lee Fatigue Scale. Latent profile analysis (LPA) was used to identify distinct subgroups. Results Three latent classes were identified for morning fatigue (i.e., Low (31.8%), High (51.4%), and Very High (16.8%)) and for evening evening fatigue (i.e., Moderate (20.0%), High (21.8%), and Very High (58.2%)). Most of the disease and treatment characteristics did not distinguish among the morning and evening fatigue classes. Compared to the Low class, patients in the High and Very High morning fatigue class were younger, had a lower functional status and higher level of comorbidity. Compared to the Moderate class, patients in the Very High evening fatigue class were younger, more likely to be female, had child care responsibilities, had a lower functional status, and a higher level of comorbidity. Conclusion LPA allows for the identification of risk factors for more severe fatigue. Since an overlap was not observed across the morning and evening fatigue classes and unique predictors for morning and evening fatigue were identified, these findings suggest that morning and evening fatigue may have distinct underlying mechanisms. PMID:26361758

Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis

PubMed Central

Erson-Omay, E. Zeynep; Çağlayan, Ahmet Okay; Schultz, Nikolaus; Weinhold, Nils; Omay, S. Bülent; Özduman, Koray; Köksal, Yavuz; Li, Jie; Serin Harmancı, Akdes; Clark, Victoria; Carrión-Grant, Geneive; Baranoski, Jacob; Çağlar, Caner; Barak, Tanyeri; Coşkun, Süleyman; Baran, Burçin; Köse, Doğan; Sun, Jia; Bakırcıoğlu, Mehmet; Moliterno Günel, Jennifer; Pamir, M. Necmettin; Mishra-Gorur, Ketu; Bilguvar, Kaya; Yasuno, Katsuhito; Vortmeyer, Alexander; Huttner, Anita J.; Sander, Chris; Günel, Murat

2015-01-01

Background Malignant high-grade gliomas (HGGs), including the most aggressive form, glioblastoma multiforme, show significant clinical and genomic heterogeneity. Despite recent advances, the overall survival of HGGs and their response to treatment remain poor. In order to gain further insight into disease pathophysiology by correlating genomic landscape with clinical behavior, thereby identifying distinct HGG molecular subgroups associated with improved prognosis, we performed a comprehensive genomic analysis. Methods We analyzed and compared 720 exome-sequenced gliomas (136 from Yale, 584 from The Cancer Genome Atlas) based on their genomic, histological, and clinical features. Results We identified a subgroup of HGGs (6 total, 4 adults and 2 children) that harbored a statistically significantly increased number of somatic mutations (mean = 9257.3 vs 76.2, P = .002). All of these “ultramutated” tumors harbored somatic mutations in the exonuclease domain of the polymerase epsilon gene (POLE), displaying a distinctive genetic profile, characterized by genomic stability and increased C-to-A transversions. Histologically, they all harbored multinucleated giant or bizarre cells, some with predominant infiltrating immune cells. One adult and both pediatric patients carried homozygous germline mutations in the mutS homolog 6 (MSH6) gene. In adults, POLE mutations were observed in patients younger than 40 years and were associated with a longer progression-free survival. Conclusions We identified a genomically, histologically, and clinically distinct subgroup of HGGs that harbored somatic POLE mutations and carried an improved prognosis. Identification of distinctive molecular and pathological HGG phenotypes has implications not only for improved classification but also for potential targeted treatments. PMID:25740784

Profiling CCK-mediated pancreatic growth: the dynamic genetic program and the role of STATs as potential regulators.

PubMed

Gurda, Grzegorz T; Wang, Jackie Y; Guo, LiLi; Ernst, Stephen A; Williams, John A

2012-01-18

Feeding mice with protease inhibitor (PI) leads to increased endogenous cholecystokinin (CCK) release and results in pancreatic growth. This adaptive response requires calcineurin (CN)-NFAT and AKT-mTOR pathways, but the genes involved, the dynamics of their expression, and other regulatory pathways remain unknown. Here, we examined the early (1-8 h) transcriptional program that underlies pancreatic growth. We found 314 upregulated and 219 downregulated genes with diverse temporal and functional profiles. Several new identifications include the following: stress response genes Gdf15 and Txnip, metabolic mediators Pitpnc1 and Hmges2, as well as components of growth factor response Fgf21, Atf3, and Egr1. The genes fell into seven self-organizing clusters, each with a distinct pattern of expression; a representative gene within each of the upregulated clusters (Egr1, Gadd45b, Rgs2, and Serpinb1a) was validated by qRT-PCR. Genes up at any point throughout the time course and CN-dependent genes were subjected to further bioinformatics-based networking and promoter analysis, yielding STATs as potential transcriptional regulators. As shown by PCR, qPCR, and Western blots, the active phospho-form of STAT3 and the Jak-STAT feedback inhibitor Socs2 were both increased throughout early pancreatic growth. Moreover, immunohistochemistry showed a CCK-dependent and acinar cell-specific increase in nuclear localization of p-STAT3, with >75% nuclear occupancy in PI-fed mice vs. <0.1% in controls. Thus, the study identified novel genes likely to be important for CCK-driven pancreatic growth, characterized and biologically validated the dynamic pattern of their expression and investigated STAT-Socs signaling as a new player in this trophic response.

Direct profiling of environmental microbial populations by thermal dissociation analysis of native rRNAs hybridized to oligonucleotide microarrays

NASA Technical Reports Server (NTRS)

El Fantroussi, Said; Urakawa, Hidetoshi; Bernhard, Anne E.; Kelly, John J.; Noble, Peter A.; Smidt, H.; Yershov, G. M.; Stahl, David A.

2003-01-01

Oligonucleotide microarrays were used to profile directly extracted rRNA from environmental microbial populations without PCR amplification. In our initial inspection of two distinct estuarine study sites, the hybridization patterns were reproducible and varied between estuarine sediments of differing salinities. The determination of a thermal dissociation curve (i.e., melting profile) for each probe-target duplex provided information on hybridization specificity, which is essential for confirming adequate discrimination between target and nontarget sequences.

Managing the genomic revolution in cancer diagnostics.

PubMed

Nguyen, Doreen; Gocke, Christopher D

2017-08-01

Molecular tumor profiling is now a routine part of patient care, revealing targetable genomic alterations and molecularly distinct tumor subtypes with therapeutic and prognostic implications. The widespread adoption of next-generation sequencing technologies has greatly facilitated clinical implementation of genomic data and opened the door for high-throughput multigene-targeted sequencing. Herein, we discuss the variability of cancer genetic profiling currently offered by clinical laboratories, the challenges of applying rapidly evolving medical knowledge to individual patients, and the need for more standardized population-based molecular profiling.

How Does Exposure to Violence Affect School Delay and Academic Motivation for Adolescents Living in Socioeconomically Disadvantaged Communities in South Africa?

PubMed

Herrero Romero, Rocio; Hall, James; Cluver, Lucie; Meinck, Franziska; Hinde, Eleanor

2018-06-01

To date, little is known about the effects of violence on the educational outcomes of adolescents in disadvantaged communities in South Africa. In response, self-report data were collected from a socioeconomically disadvantaged sample of 503 adolescents aged 10 to 18 participating in a child abuse prevention trial in the Eastern Cape. Adolescents were purposively selected in the trial. This study applies Latent Profile Analysis (LPA) to examine relationships between past-month exposure to violence, school delay, and academic motivation. About 93.8% of adolescents in the sample experienced poly-violence-exposure to at least two forms of violence in the past month. Results identified two distinct profiles in the socioeconomically disadvantaged sample: Profile 1, adolescents exposed to more frequent poly-violence, and Profile 2, adolescents exposed to less frequent poly-violence. Being exposed to more frequent poly-violence was associated with greater risk of school delay-based on age-appropriate grade in South Africa. However, being exposed to more frequent poly-violence was not associated with lower academic motivation-adolescents showed high rates of wanting to achieve. Our findings suggest that exposure to more frequent poly-violence increases risk of school delay among adolescents from disadvantaged communities, while not affecting their academic motivation. Thus, although adolescents maintained aspirations and goals to do well at school, exposure to high frequency of violence affected their capacity to fulfill these aims.

Cell culture media supplementation of infrequently used sugars for the targeted shifting of protein glycosylation profiles.

PubMed

Hossler, Patrick; Racicot, Christopher; Chumsae, Christopher; McDermott, Sean; Cochran, Keith

2017-03-01

Mammalian cells in culture rely on sources of carbohydrates to supply the energy requirements for proliferation. In addition, carbohydrates provide a large source of the carbon supply for supporting various other metabolic activities, including the intermediates involved in the protein glycosylation pathway. Glucose and galactose, in particular, are commonly used sugars in culture media for these purposes. However, there exists a very large repertoire of other sugars in nature, and many that have been chemically synthesized. These sugars are particularly interesting because they can be utilized by cells in culture in distinct ways. In the present work it has been found that many infrequently used sugars, and the corresponding cellular response towards them as substrates, led to differences in the protein N-glycosylation profile of a recombinant glycoprotein. The selective media supplementation of raffinose, trehalose, turanose, palatinose, melezitose, psicose, lactose, lactulose, and mannose were found to be capable of redirecting N-glycan oligosaccharide profiles. Despite this shifting of protein glycosylation, there were no other adverse changes in culture performance, including both cell growth and cellular productivity over a wide range of supplemented sugar concentrations. The approach presented highlights a potential means towards both the targeted shifting of protein glycosylation profiles and ensuring recombinant protein comparability, which up to this point in time has remained under-appreciated for these under-utilized compounds. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:511-522, 2017. © 2017 American Institute of Chemical Engineers.

IL-23-induced macrophage polarization and its pathological roles in mice with imiquimod-induced psoriasis.

PubMed

Hou, Yuzhu; Zhu, Linnan; Tian, Hongling; Sun, Hai-Xi; Wang, Ruoyu; Zhang, Lianfeng; Zhao, Yong

2018-03-05

Macrophages acquire distinct phenotypes during tissue stress and inflammatory responses. Macrophages are roughly categorized into two different subsets named inflammatory M1 and anti-inflammatory M2 macrophages. We herein identified a unique pathogenic macrophage subpopulation driven by IL-23 with a distinct gene expression profile including defined types of cytokines. The freshly isolated resting mouse peritoneal macrophages were stimulated with different cytokines in vitro, the expression of cytokines and chemokines were detected by microarray, real-time PCR, ELISA and multiple colors flow cytometry. Adoptive transfer of macrophages and imiquimod-induced psoriasis mice were used. In contrast to M1- and M2-polarized macrophages, IL-23-treated macrophages produce large amounts of IL-17A, IL-22 and IFN-γ. Biochemical and molecular studies showed that IL-23 induces IL-17A expression in macrophages through the signal transducer and activator of transcription 3 (STAT3)-retinoid related orphan receptor-γ T (RORγT) pathway. T-bet mediates the IFN-γ production in IL-23-treated macrophages. Importantly, IL-23-treated macrophages significantly promote the dermatitis pathogenesis in a psoriasis-like mouse model. IL-23-treated resting macrophages express a distinctive gene expression prolife compared with M1 and M2 macrophages. The identification of IL-23-induced macrophage polarization may help us to understand the contribution of macrophage subpopulation in Th17-cytokines-related pathogenesis.

Latent profile analysis of students' motivation and outcomes in mathematics: an organismic integration theory perspective.

PubMed

Wang, Chee Keng John; Liu, Woon Chia; Nie, Youyan; Chye, Yen Leng Stefanie; Lim, Boon San Coral; Liem, Gregory Arief; Tay, Eng Guan; Hong, Ying-Yi; Chiu, Chi-Yue

2017-05-01

The purpose of the current study was to identify the motivation profiles at the intraindividual level using a latent profile analyses (LPA) approach. A total of 1151 secondary school students aged 13 to 17 years old from Singapore took part in the study. Using LPA, four distinct motivational profiles were identified based on four motivation regulations. Profile 1 has very low introjected and low autonomous motivation (6% of sample). Profile 2 had high external and identified regulations and very low intrinsic regulation (10%). Profile 3 consisted of students with high identified and intrinsic regulations (51%). Profile 4 had moderately low identified and intrinsic regulations (33%). The results showed that the four profiles differed significantly in terms of effort, competence, value, and time spent on math beyond homework. The best profile (Profile 3) reported highest scores in effort, value, competence and time spent on Math beyond homework. The worst profile (Profile 1) reported lowest scores in all the four outcome variables.

Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands.

PubMed

Procházková, Jiřina; Strapáčová, Simona; Svržková, Lucie; Andrysík, Zdeněk; Hýžďalová, Martina; Hrubá, Eva; Pěnčíková, Kateřina; Líbalová, Helena; Topinka, Jan; Kléma, Jiří; Espinosa, Joaquín M; Vondráček, Jan; Machala, Miroslav

2018-08-01

Exposure to persistent ligands of aryl hydrocarbon receptor (AhR) has been found to cause lung cancer in experimental animals, and lung adenocarcinomas are often associated with enhanced AhR expression and aberrant AhR activation. In order to better understand the action of toxic AhR ligands in lung epithelial cells, we performed global gene expression profiling and analyze TCDD-induced changes in A549 transcriptome, both sensitive and non-sensitive to CH223191 co-treatment. Comparison of our data with results from previously reported microarray and ChIP-seq experiments enabled us to identify candidate genes, which expression status reflects exposure of lung cancer cells to TCDD, and to predict processes, pathways (e.g. ER stress, Wnt/β-cat, IFNɣ, EGFR/Erbb1), putative TFs (e.g. STAT, AP1, E2F1, TCF4), which may be implicated in adaptive response of lung cells to TCDD-induced AhR activation. Importantly, TCDD-like expression fingerprint of selected genes was observed also in A549 cells exposed acutely to both toxic (benzo[a]pyrene, benzo[k]fluoranthene) and endogenous AhR ligands (2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl ester and 6-formylindolo[3,2-b]carbazole). Overall, our results suggest novel cellular candidates, which could help to improve monitoring of AhR-dependent transcriptional activity during acute exposure of lung cells to distinct types of environmental pollutants. Copyright © 2018 Elsevier B.V. All rights reserved.

Kinome and Transcriptome Profiling Reveal Broad and Distinct Activities of Erlotinib, Sunitinib, and Sorafenib in the Mouse Heart and Suggest Cardiotoxicity From Combined Signal Transducer and Activator of Transcription and Epidermal Growth Factor Receptor Inhibition.

PubMed

Stuhlmiller, Timothy J; Zawistowski, Jon S; Chen, Xin; Sciaky, Noah; Angus, Steven P; Hicks, Sean T; Parry, Traci L; Huang, Wei; Beak, Ju Youn; Willis, Monte S; Johnson, Gary L; Jensen, Brian C

2017-10-19

Most novel cancer therapeutics target kinases that are essential to tumor survival. Some of these kinase inhibitors are associated with cardiotoxicity, whereas others appear to be cardiosafe. The basis for this distinction is unclear, as are the molecular effects of kinase inhibitors in the heart. We administered clinically relevant doses of sorafenib, sunitinib (cardiotoxic multitargeted kinase inhibitors), or erlotinib (a cardiosafe epidermal growth factor receptor inhibitor) to mice daily for 2 weeks. We then compared the effects of these 3 kinase inhibitors on the cardiac transcriptome using RNAseq and the cardiac kinome using multiplexed inhibitor beads coupled with mass spectrometry. We found unexpectedly broad molecular effects of all 3 kinase inhibitors, suggesting that target kinase selectivity does not define either the molecular response or the potential for cardiotoxicity. Using in vivo drug administration and primary cardiomyocyte culture, we also show that the cardiosafety of erlotinib treatment may result from upregulation of the cardioprotective signal transducer and activator of transcription 3 pathway, as co-treatment with erlotinib and a signal transducer and activator of transcription inhibitor decreases cardiac contractile function and cardiomyocyte fatty acid oxidation. Collectively our findings indicate that preclinical kinome and transcriptome profiling may predict the cardiotoxicity of novel kinase inhibitors, and suggest caution for the proposed therapeutic strategy of combined signal transducer and activator of transcription/epidermal growth factor receptor inhibition for cancer treatment. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Molecular mechanisms of memory in imprinting.

PubMed

Solomonia, Revaz O; McCabe, Brian J

2015-03-01

Converging evidence implicates the intermediate and medial mesopallium (IMM) of the domestic chick forebrain in memory for a visual imprinting stimulus. During and after imprinting training, neuronal responsiveness in the IMM to the familiar stimulus exhibits a distinct temporal profile, suggesting several memory phases. We discuss the temporal progression of learning-related biochemical changes in the IMM, relative to the start of this electrophysiological profile. c-fos gene expression increases <15 min after training onset, followed by a learning-related increase in Fos expression, in neurons immunopositive for GABA, taurine and parvalbumin (not calbindin). Approximately simultaneously or shortly after, there are increases in phosphorylation level of glutamate (AMPA) receptor subunits and in releasable neurotransmitter pools of GABA and taurine. Later, the mean area of spine synapse post-synaptic densities, N-methyl-D-aspartate receptor number and phosphorylation level of further synaptic proteins are elevated. After ∼ 15 h, learning-related changes in amounts of several synaptic proteins are observed. The results indicate progression from transient/labile to trophic synaptic modification, culminating in stable recognition memory. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Molecular mechanisms of memory in imprinting

PubMed Central

Solomonia, Revaz O.; McCabe, Brian J.

2015-01-01

Converging evidence implicates the intermediate and medial mesopallium (IMM) of the domestic chick forebrain in memory for a visual imprinting stimulus. During and after imprinting training, neuronal responsiveness in the IMM to the familiar stimulus exhibits a distinct temporal profile, suggesting several memory phases. We discuss the temporal progression of learning-related biochemical changes in the IMM, relative to the start of this electrophysiological profile. c-fos gene expression increases <15 min after training onset, followed by a learning-related increase in Fos expression, in neurons immunopositive for GABA, taurine and parvalbumin (not calbindin). Approximately simultaneously or shortly after, there are increases in phosphorylation level of glutamate (AMPA) receptor subunits and in releasable neurotransmitter pools of GABA and taurine. Later, the mean area of spine synapse post-synaptic densities, N-methyl-d-aspartate receptor number and phosphorylation level of further synaptic proteins are elevated. After ∼15 h, learning-related changes in amounts of several synaptic proteins are observed. The results indicate progression from transient/labile to trophic synaptic modification, culminating in stable recognition memory. PMID:25280906

Facile design and stabilization of a novel one-dimensional silicon-based photonic crystal microcavity

NASA Astrophysics Data System (ADS)

Salem, Mohamed Shaker; Ibrahim, Shaimaa Moustafa; Amin, Mohamed

2017-07-01

A novel silicon-based optical microcavity composed of a defect layer sandwiched between two parallel rugate mirrors is created by the electrochemical anodization of silicon in a hydrofluoric acid-based electrolyte using a precisely controlled current density profile. The profile consists of two sinusoidally modulated current waveforms separated by a fixed current that is applied to produce a defect layer between the mirrors. The spectral response of the rugate-based microcavity is simulated using the transfer matrix method and compared to the conventional Bragg-based microcavity. It is found that the resonance position of both microcavities is unchanged. However, the rugate-based microcavity exhibits a distinct reduction of the sidebands' intensity. Further attenuation of the sidebands' intensity is obtained by creating refractive index matching layers with optimized thickness at the bottom and top of the rugate-based microcavity. In order to stabilize the produced microcavity against natural oxidation, atomic layer deposition of an ultra-thin titanium dioxide layer on the pore wall is carried out followed by thermal annealing. The microcavity resonance position shows an observable sensitivity to the deposition and annealing processes.

Characterization of the secreted cathepsin B cysteine proteases family of the carcinogenic liver fluke Clonorchis sinensis.

PubMed

Chen, Wenjun; Wang, Xiaoyun; Lv, Xiaoli; Tian, Yanli; Xu, Yanquan; Mao, Qiang; Shang, Mei; Li, Xuerong; Huang, Yan; Yu, Xinbing

2014-09-01

Clonorchis sinensis excretory/secretory products (ESP) have gained high attentions because of their potential to be vaccine candidates and drug targets in C. sinensis prevention. In this study, we extensively profiled the characteristics of four C. sinensis cathepsin B cysteine proteases (CsCB1, CsCB2, CsCB3, and CsCB4). Bioinformatics analysis showed all CsCBs contained signal peptides at the N-terminal. Functional domains and residues were found in CsCB sequences. We expressed four CsCBs and profiled immune responses followed by vaccine trials. Recombinant CsCBs could induce high IgG titers, indicating high immunogenicity of CsCB family. Additionally, ELISA results showed that both IgG1 and IgG2a levels apparently increased post-immunization with all four CsCBs, showing that combined Th1/Th2 immune responses were triggered by CsCB family. Both Real-time polymerase chain reaction (RT-PCR) and Western blotting confirmed that four CsCBs have distinct expression patterns in C. sinensis life stages. More importantly, we validated our hypothesis that CsCBs were C. sinensis excretory/secretory products. CsCBs could be recognized by C. sinensis-infected sera throughout the infection period, indicating that secreted CsCBs are immune triggers during C. sinensis infection. The protective effect was assessed by comparing the worm burden and egg per gram (EPG) between CsCB group and control group, showing that worm burden (P < 0.01) and EPG (P < 0.01) in CsCB2 and CsCB3 groups were significantly lower than in control group. In conclusion, we profiled secreted cathepsin B cysteine proteases family for the first time and demonstrated that all CsCB family were C. sinensis excretory/secretory products that may regulate host immune responses.

Pharmacodynamic response profiles of anxiolytic and sedative drugs.

PubMed

Chen, Xia; Broeyer, Freerk; de Kam, Marieke; Baas, Joke; Cohen, Adam; van Gerven, Joop

2017-05-01

Centrally-acting acutely anxiolytic drugs, such as benzodiazepines, barbiturates and gabapentinoids, affect various central nervous system (CNS) functions, which reflects not only their anxiolytic effects but also neuropsychological side-effects. To validate the pharmacodynamic biomarkers for GABA-ergic anxiolytics, this study determined the pharmacodynamics of two anxiolytics and a nonanxiolytic control, and linked them to their anxiolytic and sedative effects, during an anxiety-challenge study day. Twenty healthy volunteers were randomized in this placebo-controlled, double-blind, four-way cross-over study with single-dose alprazolam (1 mg), diphenhydramine (50 mg), pregabalin (200 mg) or placebo. The Neurocart was used between repeated fear-potentiated startle assessments. Thus, the potential influence of anxiety on CNS pharmacodynamic markers could be examined. Compared to placebo, VAS calmness increased with alprazolam (2.0 mm) and pregabalin (2.5 mm) but not with diphenhydramine. Saccadic peak velocity (SPV) declined after alprazolam (-57 ° s -1 ) and pregabalin (-28 ° s -1 ), more than with diphenhydramine (-14 ° s -1 ); so did smooth pursuit. The average responses of SPV and smooth pursuit were significantly correlated with the drug-induced increases in VAS calmness . The SPV-relative responses of VAS alertness , body-sway and adaptive-tracking also differed among alprazolam, pregabalin and diphenhydramine. Compared with the antihistaminergic sedative diphenhydramine, alprazolam and pregabalin caused larger SPV reduction, which was correlated with simultaneous improvement of subjective calmness, during a study day in which anxiety was stimulated repeatedly. The different effect profiles of the three drugs are in line with their pharmacological distinctions. These findings corroborate the profiling of CNS effects to demonstrate pharmacological selectivity, and further support SPV as biomarker for anxiolysis involving GABA-ergic neurons. The study also supports the use of prolonged mild threat to demonstrate anxiolytic effects in healthy volunteers. © 2016 The British Pharmacological Society.

The Role of Religiousness/Spirituality in Health-Related Quality of Life Among Adolescents with HIV: A Latent Profile Analysis

PubMed Central

Kimmel, Allison L.; Cheng, Yao Iris; Wang, Jichuan

2016-01-01

The purpose of this study was to determine whether distinct latent profiles of religiousness/spirituality exist for ALWH, and if so, are latent profile memberships associated with health-related quality of life (HRQoL). Latent profile analysis of religiosity identified four profiles/groups. Compared to the other three groups, higher levels of emotional well-being were found among young perinatally infected adolescents who attended religious services, but who did not pray privately, feel God's presence or identify as religious or spiritual. Social HRQoL was significantly higher among the highest overall religious/spiritual group. Understanding adolescent profiles of religiousness/spirituality on HRQoL could inform faith-based interventions. PMID:27071797

The Role of Religiousness/Spirituality in Health-Related Quality of Life Among Adolescents with HIV: A Latent Profile Analysis.

PubMed

Lyon, Maureen E; Kimmel, Allison L; Cheng, Yao Iris; Wang, Jichuan

2016-10-01

The purpose of this study was to determine whether distinct latent profiles of religiousness/spirituality exist for ALWH, and if so, are latent profile memberships associated with health-related quality of life (HRQoL). Latent profile analysis of religiosity identified four profiles/groups. Compared to the other three groups, higher levels of emotional well-being were found among young perinatally infected adolescents who attended religious services, but who did not pray privately, feel God's presence or identify as religious or spiritual. Social HRQoL was significantly higher among the highest overall religious/spiritual group. Understanding adolescent profiles of religiousness/spirituality on HRQoL could inform faith-based interventions. Trial registration NCT01289444.

Contemporaneous Social Environment and the Architecture of Late-Life Gene Expression Profiles.

PubMed

Levine, Morgan E; Crimmins, Eileen M; Weir, David R; Cole, Steve W

2017-09-01

Environmental or social challenges can stimulate a cascade of coordinated physiological changes in stress response systems. Unfortunately, chronic activation of these adaptations under conditions such as low socioeconomic status (SES) can have negative consequences for long-term health. While there is substantial evidence tying low SES to increased disease risk and reduced life expectancy, the underlying biology remains poorly understood. Using pilot data on 120 older adults from the Health and Retirement Study (United States, 2002-2010), we examined the associations between SES and gene expression levels in adulthood, with particular focus on a gene expression program known as the conserved transcriptional response to adversity. We also used a bioinformatics-based approach to assess the activity of specific gene regulation pathways involved in inflammation, antiviral responses, and stress-related neuroendocrine signaling. We found that low SES was related to increased expression of conserved transcriptional response to adversity genes and distinct patterns of proinflammatory, antiviral, and stress signaling (e.g., sympathetic nervous system and hypothalamic-pituitary-adrenal axis) transcription factor activation. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Autism Phenotypes in Tuberous Sclerosis Complex: Diagnostic and Treatment Considerations.

PubMed

Gipson, Tanjala T; Poretti, Andrea; Thomas, Emily A; Jenkins, Kosunique T; Desai, Sonal; Johnston, Michael V

2015-12-01

Tuberous sclerosis complex is a multisystem, chronic genetic condition characterized by systemic growth of benign tumors and often accompanied by epilepsy, autism spectrum disorders, and intellectual disability. Nonetheless, the neurodevelopmental phenotype of these patients is not often detailed. The authors describe 3 individuals with tuberous sclerosis complex who share common characteristics that can help to identify a distinct profile of autism spectrum disorder. These findings include typical cognitive development, expressive and pragmatic language deficits, and anxiety. The authors also describe features specific to tuberous sclerosis complex that require consideration before diagnosing an autism spectrum disorder. Identifying distinct profiles of autism spectrum disorder in tuberous sclerosis complex can help optimize treatment across the life span. © The Author(s) 2015.

Toxicological profile of ultrapure 2,2',3,4,4',5,5'-heptachlorbiphenyl (PCB 180) in adult rats.

PubMed

Viluksela, Matti; Heikkinen, Päivi; van der Ven, Leo T M; Rendel, Filip; Roos, Robert; Esteban, Javier; Korkalainen, Merja; Lensu, Sanna; Miettinen, Hanna M; Savolainen, Kari; Sankari, Satu; Lilienthal, Hellmuth; Adamsson, Annika; Toppari, Jorma; Herlin, Maria; Finnilä, Mikko; Tuukkanen, Juha; Leslie, Heather A; Hamers, Timo; Hamscher, Gerd; Al-Anati, Lauy; Stenius, Ulla; Dervola, Kine-Susann; Bogen, Inger-Lise; Fonnum, Frode; Andersson, Patrik L; Schrenk, Dieter; Halldin, Krister; Håkansson, Helen

2014-01-01

PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterization of NDL-PCBs is confounded by the presence of highly potent dioxin-like impurities. We used ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose toxicity study in young adult rats extended to cover endocrine and behavioral effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5 females were given total doses of 0, 3, 10, 30, 100, 300, 1000 or 1700 mg PCB 180/kg body weight by gavage. Dose-responses were analyzed using benchmark dose modeling based on dose and adipose tissue PCB concentrations. Body weight gain was retarded at 1700 mg/kg during loading dosing, but recovered thereafter. The most sensitive endpoint of toxicity that was used for risk characterization was altered open field behavior in females; i.e. increased activity and distance moved in the inner zone of an open field suggesting altered emotional responses to unfamiliar environment and impaired behavioral inhibition. Other dose-dependent changes included decreased serum thyroid hormones with associated histopathological changes, altered tissue retinoid levels, decreased hematocrit and hemoglobin, decreased follicle stimulating hormone and luteinizing hormone levels in males and increased expression of DNA damage markers in liver of females. Dose-dependent hypertrophy of zona fasciculata cells was observed in adrenals suggesting activation of cortex. There were gender differences in sensitivity and toxicity profiles were partly different in males and females. PCB 180 adipose tissue concentrations were clearly above the general human population levels, but close to the levels in highly exposed populations. The results demonstrate a distinct toxicological profile of PCB 180 with lack of dioxin-like properties required for assignment of WHO toxic equivalency factor. However, PCB 180 shares several toxicological targets with dioxin-like compounds emphasizing the potential for interactions.

Toxicological Profile of Ultrapure 2,2′,3,4,4′,5,5′-Heptachlorbiphenyl (PCB 180) in Adult Rats

PubMed Central

Viluksela, Matti; Heikkinen, Päivi; van der Ven, Leo T. M.; Rendel, Filip; Roos, Robert; Esteban, Javier; Korkalainen, Merja; Lensu, Sanna; Miettinen, Hanna M.; Savolainen, Kari; Sankari, Satu; Lilienthal, Hellmuth; Adamsson, Annika; Toppari, Jorma; Herlin, Maria; Finnilä, Mikko; Tuukkanen, Juha; Leslie, Heather A.; Hamers, Timo; Hamscher, Gerd; Al-Anati, Lauy; Stenius, Ulla; Dervola, Kine-Susann; Bogen, Inger-Lise; Fonnum, Frode; Andersson, Patrik L.; Schrenk, Dieter; Halldin, Krister; Håkansson, Helen

2014-01-01

PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterization of NDL-PCBs is confounded by the presence of highly potent dioxin-like impurities. We used ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose toxicity study in young adult rats extended to cover endocrine and behavioral effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5 females were given total doses of 0, 3, 10, 30, 100, 300, 1000 or 1700 mg PCB 180/kg body weight by gavage. Dose-responses were analyzed using benchmark dose modeling based on dose and adipose tissue PCB concentrations. Body weight gain was retarded at 1700 mg/kg during loading dosing, but recovered thereafter. The most sensitive endpoint of toxicity that was used for risk characterization was altered open field behavior in females; i.e. increased activity and distance moved in the inner zone of an open field suggesting altered emotional responses to unfamiliar environment and impaired behavioral inhibition. Other dose-dependent changes included decreased serum thyroid hormones with associated histopathological changes, altered tissue retinoid levels, decreased hematocrit and hemoglobin, decreased follicle stimulating hormone and luteinizing hormone levels in males and increased expression of DNA damage markers in liver of females. Dose-dependent hypertrophy of zona fasciculata cells was observed in adrenals suggesting activation of cortex. There were gender differences in sensitivity and toxicity profiles were partly different in males and females. PCB 180 adipose tissue concentrations were clearly above the general human population levels, but close to the levels in highly exposed populations. The results demonstrate a distinct toxicological profile of PCB 180 with lack of dioxin-like properties required for assignment of WHO toxic equivalency factor. However, PCB 180 shares several toxicological targets with dioxin-like compounds emphasizing the potential for interactions. PMID:25137063

The Mouse Cortical Connectome, Characterized by an Ultra-Dense Cortical Graph, Maintains Specificity by Distinct Connectivity Profiles.

PubMed

Gămănuţ, Răzvan; Kennedy, Henry; Toroczkai, Zoltán; Ercsey-Ravasz, Mária; Van Essen, David C; Knoblauch, Kenneth; Burkhalter, Andreas

2018-02-07

The inter-areal wiring pattern of the mouse cerebral cortex was analyzed in relation to a refined parcellation of cortical areas. Twenty-seven retrograde tracer injections were made in 19 areas of a 47-area parcellation of the mouse neocortex. Flat mounts of the cortex and multiple histological markers enabled detailed counts of labeled neurons in individual areas. The observed log-normal distribution of connection weights to each cortical area spans 5 orders of magnitude and reveals a distinct connectivity profile for each area, analogous to that observed in macaques. The cortical network has a density of 97%, considerably higher than the 66% density reported in macaques. A weighted graph analysis reveals a similar global efficiency but weaker spatial clustering compared with that reported in macaques. The consistency, precision of the connectivity profile, density, and weighted graph analysis of the present data differ significantly from those obtained in earlier studies in the mouse. Copyright © 2017 Elsevier Inc. All rights reserved.

The morphologies of breast cancer cell lines in three-dimensionalassays correlate with their profiles of gene expression

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

Kenny, Paraic A.; Lee, Genee Y.; Myers, Connie A.

2007-01-31

3D cell cultures are rapidly becoming the method of choice for the physiologically relevant modeling of many aspects of non-malignant and malignant cell behavior ex vivo. Nevertheless, only a limited number of distinct cell types have been evaluated in this assay to date. Here we report the first large scale comparison of the transcriptional profiles and 3D cell culture phenotypes of a substantial panel of human breast cancer cell lines. Each cell line adopts a colony morphology of one of four main classes in 3D culture. These morphologies reflect, at least in part, the underlying gene expression profile and proteinmore » expression patterns of the cell lines, and distinct morphologies were also associated with tumor cell invasiveness and with cell lines originating from metastases. We further demonstrate that consistent differences in genes encoding signal transduction proteins emerge when even tumor cells are cultured in 3D microenvironments.« less

Behavioral Risk Profile of Men Who Have Sex with Men in Beijing, China: Results from a Cross-sectional Survey with Randomized Response Techniques.

PubMed

Geng, Guo-Zhu; Gao, Ge; Ruan, Yu-Hua; Yu, Ming-Run; Zhou, Yun-Hua

2016-03-05

Human immunodeficiency virus (HIV) is spreading rapidly among men who have sex with men (MSM) in China. Anonymous questionnaires or direct interviews have been frequently used to study their behavior. The aim of the study was to describe the behavioral risk profile of the MSM in Beijing using the randomized response techniques (RRTs). A cross-sectional survey of sexual behavior among a sample of MSM was conducted in two HIV counseling and testing clinics in Beijing. The survey was carried out with an anonymous questionnaire containing sensitive questions on sexual behavior. To obtain the honest responses to the sensitive questions, three distinctive RRTs were used in the questionnaire: (1) Additive randomized response model for quantitative questions, (2) randomized response model for multiple choice questions, and (3) Simmons randomized response model for binomial questions. Formulae for the point estimate, variance, and confidence interval (CI) were provided for each specific model. Using RRTs in a sample of 659 participants, the mean age at first homosexual encounter was estimated to be 21.7 years (95% CI: 21.2-22.2), and each had sex with about three (2.9, 95% CI: 2.4-3.4) male partners on average in the past month. The estimated rate for consistent condom use was 56.4% (95% CI: 50.1-62.8%). In addition, condom was estimated to be used among 80.0% (95% CI: 74.1-85.9%) of the population during last anal sex with a male partner. Our study employed RRTs in a survey containing questions on sexual behavior among MSM, and the results showed that RRT might be a useful tool to obtain truthful feedback on sensitive information such as sexual behavior from the respondents, especially in traditional Chinese cultural settings.

Parent Prevention Communication Profiles and Adolescent Substance Use: A Latent Profile Analysis and Growth Curve Model

PubMed Central

Choi, Hye Jeong; Miller-Day, Michelle; Shin, YoungJu; Hecht, Michael L.; Pettigrew, Jonathan; Krieger, Janice L.; Lee, JeongKyu; Graham, John W.

2017-01-01

This current study identifies distinct parent prevention communication profiles and examines whether youth with different parental communication profiles have varying substance use trajectories over time. Eleven schools in two rural school districts in the Midwestern United States were selected, and 784 students were surveyed at three time points from the beginning of 7th grade to the end of 8th grade. A series of latent profile analyses were performed to identify discrete profiles/subgroups of substance-specific prevention communication (SSPC). The results revealed a 4-profile model of SSPC: Active-Open, Passive-Open, Active-Silent, and Passive-Silent. A growth curve model revealed different rates of lifetime substance use depending on the youth’s SSPC profile. These findings have implications for parenting interventions and tailoring messages for parents to fit specific SSPC profiles. PMID:29056872

Variations in Decision-Making Profiles by Age and Gender: A Cluster-Analytic Approach

PubMed Central

Delaney, Rebecca; Strough, JoNell; Parker, Andrew M.; de Bruin, Wandi Bruine

2015-01-01

Using cluster-analysis, we investigated whether rational, intuitive, spontaneous, dependent, and avoidant styles of decision making (Scott & Bruce, 1995) combined to form distinct decision-making profiles that differed by age and gender. Self-report survey data were collected from 1,075 members of RAND’s American Life Panel (56.2% female, 18–93 years, Mage = 53.49). Three decision-making profiles were identified: affective/experiential, independent/self-controlled, and an interpersonally-oriented dependent profile. Older people were less likely to be in the affective/experiential profile and more likely to be in the independent/self-controlled profile. Women were less likely to be in the affective/experiential profile and more likely to be in the interpersonally-oriented dependent profile. Interpersonally-oriented profiles are discussed as an overlooked but important dimension of how people make important decisions. PMID:26005238

Individual differences in learning and transfer: stable tendencies for learning exemplars versus abstracting rules.

PubMed

McDaniel, Mark A; Cahill, Michael J; Robbins, Mathew; Wiener, Chelsea

2014-04-01

We hypothesize that during training some learners may focus on acquiring the particular exemplars and responses associated with the exemplars (termed exemplar learners), whereas other learners attempt to abstract underlying regularities reflected in the particular exemplars linked to an appropriate response (termed rule learners). Supporting this distinction, after training (on a function-learning task), participants displayed an extrapolation profile reflecting either acquisition of the trained cue-criterion associations (exemplar learners) or abstraction of the function rule (rule learners; Studies 1a and 1b). Further, working memory capacity (measured by operation span [Ospan]) was associated with the tendency to rely on rule versus exemplar processes. Studies 1c and 2 examined the persistence of these learning tendencies on several categorization tasks. Study 1c showed that rule learners were more likely than exemplar learners (indexed a priori by extrapolation profiles) to resist using idiosyncratic features (exemplar similarity) in generalization (transfer) of the trained category. Study 2 showed that the rule learners but not the exemplar learners performed well on a novel categorization task (transfer) after training on an abstract coherent category. These patterns suggest that in complex conceptual tasks, (a) individuals tend to either focus on exemplars during learning or on extracting some abstraction of the concept, (b) this tendency might be a relatively stable characteristic of the individual, and (c) transfer patterns are determined by that tendency.

Population variation in neuroendocrine activity is associated with behavioral inhibition and hemispheric brain structure in young rhesus monkeys

PubMed Central

Short, Sarah J.; Lubach, Gabriele R.; Shirtcliff, Elizabeth A.; Styner, Martin A.; Gilmore, John H.; Coe, Christopher L.

2014-01-01

Summary Population variation in hypothalamic-pituitary-adrenal (HPA) activity and reactivity was assessed in a healthy sample of 48 juvenile rhesus monkeys. Cluster analysis of the HPA profiles revealed four distinct neuroendocrine phenotypes based on six indices of HPA functioning. Behavioral reactivity was also evaluated in response to novel stimuli, and revealed marked differences between animals in the highest- and lowest-cortisol clusters. Specifically, animals in the high-cortisol cluster showed larger stress-induced cortisol responses and blunted feedback sensitivity to dexamethasone. They were also emotionally reactive, displayed more aggressive behaviors, and were less likely to approach novel objects. In contrast, monkeys in the low-cortisol cluster were more likely to approach and explore novel objects. Representative animals with high or low cortisol profiles were scanned with Magnetic Resonance Imaging to evaluate structural differences in global and regional gray matter (GM) and white matter (WM) volumes. Monkeys with higher cortisol reactivity evinced less hemispheric brain asymmetry, due to decreased GM in the right hemisphere. Stress reactivity was inversely related to global GM and positively related to total cerebrospinal fluid volume. This inverse relationship was also observed in several stress-sensitive regions, including prefrontal and frontal cortices. Our study demonstrates that population variation in pituitary-adrenal activity is related to behavioral disposition and cerebral structure in this nonhuman primate species. PMID:24954302

Molecular characterization and biological response to respiration inhibitors of Pyricularia isolates from ctenanthe and rice plants.

PubMed

Paplomatas, Epaminondas J; Pappas, Athanasios C; Syranidou, Elene

2005-07-01

The molecular profile and the biological response of isolates of Pyricularia oryzae Cavara obtained from ctenanthe to two strobilurins (azoxystrobin, kresoxim-methyl) and the phenylpyridinamine fungicide fluazinam were characterized, and compared with isolates from rice plants. Five different isozymes (alpha-esterase, lactate, malate, isocitrate and sorbitol dehydrogenases) and five random decamer primers for RAPD-PCR were used to generate molecular markers. Using unweighted pair-group with arithmetic average analysis, ctenanthe isolates were found to form a separate group distinct from that of the rice isolates for both sets of markers. Amplified polymorphic sequences of mitochondrial cytochrome b that were digested with Fnu4HI or StyI revealed no differences among Pyricularia isolates at amino acid positions 143 or 129 which confer resistance to strobilurins in several fungi. In absence of the alternative respiration inhibitor salicylhydroxamic acid (SHAM) the three fungicides showed inferior and variable efficacy, with a trend toward the rice isolate being less sensitive. The addition of SHAM enhanced the effectiveness of all fungicides against isolates regardless of their origin. Appressorium formation was the most vulnerable target of action of the respiration inhibitors and azoxystrobin the most effective. This is the first report of a comparison between the molecular profiles and sensitivities to respiration inhibitors for Pyricularia oryzae isolates from a non-gramineous host and from rice. Copyright 2005 Society of Chemical Industry

Tissue-Specific Transcriptomic Profiling of Sorghum propinquum using a Rice Genome Array

PubMed Central

Zhang, Ting; Zhao, Xiuqin; Huang, Liyu; Liu, Xiaoyue; Zong, Ying; Zhu, Linghua; Yang, Daichang; Fu, Binying

2013-01-01

Sorghum (Sorghum bicolor) is one of the world's most important cereal crops. S. propinquum is a perennial wild relative of S. bicolor with well-developed rhizomes. Functional genomics analysis of S. propinquum, especially with respect to molecular mechanisms related to rhizome growth and development, can contribute to the development of more sustainable grain, forage, and bioenergy cropping systems. In this study, we used a whole rice genome oligonucleotide microarray to obtain tissue-specific gene expression profiles of S. propinquum with special emphasis on rhizome development. A total of 548 tissue-enriched genes were detected, including 31 and 114 unique genes that were expressed predominantly in the rhizome tips (RT) and internodes (RI), respectively. Further GO analysis indicated that the functions of these tissue-enriched genes corresponded to their characteristic biological processes. A few distinct cis-elements, including ABA-responsive RY repeat CATGCA, sugar-repressive TTATCC, and GA-responsive TAACAA, were found to be prevalent in RT-enriched genes, implying an important role in rhizome growth and development. Comprehensive comparative analysis of these rhizome-enriched genes and rhizome-specific genes previously identified in Oryza longistaminata and S. propinquum indicated that phytohormones, including ABA, GA, and SA, are key regulators of gene expression during rhizome development. Co-localization of rhizome-enriched genes with rhizome-related QTLs in rice and sorghum generated functional candidates for future cloning of genes associated with rhizome growth and development. PMID:23536906

Individual Differences in Learning and Transfer: Stable Tendencies for Learning Exemplars versus Abstracting Rules

PubMed Central

McDaniel, Mark A.; Cahill, Michael J.; Robbins, Mathew; Wiener, Chelsea

2013-01-01

We hypothesize that during training some learners may focus on acquiring the particular exemplars and responses associated with the exemplars (termed exemplar learners), whereas other learners attempt to abstract underlying regularities reflected in the particular exemplars linked to an appropriate response (termed rule learners). Supporting this distinction, after training (on a function-learning task), participants either displayed an extrapolation profile reflecting acquisition of the trained cue-criterion associations (exemplar learners) or abstraction of the function rule (rule learners; Studies 1a and 1b). Further, working memory capacity (measured by Ospan) was associated with the tendency to rely on rule versus exemplar processes. Studies 1c and 2 examined the persistence of these learning tendencies on several categorization tasks. Study 1c showed that rule learners were more likely than exemplar learners (indexed a priori by extrapolation profiles) to resist using idiosyncratic features (exemplar similarity) in generalization (transfer) of the trained category. Study 2 showed that the rule learners but not the exemplar learners performed well on a novel categorization task (transfer) after training on an abstract coherent category. These patterns suggest that in complex conceptual tasks, (a) individuals tend to either focus on exemplars during learning or on extracting some abstraction of the concept, (b) this tendency might be a relatively stable characteristic of the individual, and (c) transfer patterns are determined by that tendency. PMID:23750912

Single kernel ionomic profiles are highly heritable indicators of genetic and environmental influences on elemental accumulation in maize grain (Zea mays)

USDA-ARS?s Scientific Manuscript database

The ionome, or elemental profile, of a maize kernel represents at least two distinct ideas. First, the collection of elements within the kernel are food, feed and feedstocks for people, animals and industrial processes. Second, the ionome of the kernel represents a developmental end point that can s...

L2 Motivation Profiling and the Role of Context: A Study in Exploratory Statistical Procedures

ERIC Educational Resources Information Center

Vahtrick, Lousia; de Bot, Kees

2013-01-01

Two studies were carried out in order to create distinct motivational profiles of students, examine the way in which context had an effect on motivational styles, and attempt to collaborate these findings with the L2 Motivational Self-System. The research questions for this study were concerned with ascertaining whether or not it is possible to…

Single-cell mRNA profiling reveals transcriptional heterogeneity among pancreatic circulating tumour cells.

PubMed

Lapin, Morten; Tjensvoll, Kjersti; Oltedal, Satu; Javle, Milind; Smaaland, Rune; Gilje, Bjørnar; Nordgård, Oddmund

2017-05-31

Single-cell mRNA profiling of circulating tumour cells may contribute to a better understanding of the biology of these cells and their role in the metastatic process. In addition, such analyses may reveal new knowledge about the mechanisms underlying chemotherapy resistance and tumour progression in patients with cancer. Single circulating tumour cells were isolated from patients with locally advanced or metastatic pancreatic cancer with immuno-magnetic depletion and immuno-fluorescence microscopy. mRNA expression was analysed with single-cell multiplex RT-qPCR. Hierarchical clustering and principal component analysis were performed to identify expression patterns. Circulating tumour cells were detected in 33 of 56 (59%) examined blood samples. Single-cell mRNA profiling of intact isolated circulating tumour cells revealed both epithelial-like and mesenchymal-like subpopulations, which were distinct from leucocytes. The profiled circulating tumour cells also expressed elevated levels of stem cell markers, and the extracellular matrix protein, SPARC. The expression of SPARC might correspond to an epithelial-mesenchymal transition in pancreatic circulating tumour cells. The analysis of single pancreatic circulating tumour cells identified distinct subpopulations and revealed elevated expression of transcripts relevant to the dissemination of circulating tumour cells to distant organ sites.

Neurological and Psychiatric Diseases and Their Unique Cognitive Profiles: Implications for Nursing Practice and Research

PubMed Central

Vance, David E.; Dodson, Joan E.; Watkins, Jason; Kennedy, Bridgett H.; Keltner, Norman L.

2013-01-01

To successfully negotiate and interact with one’s environment, optimal cognitive functioning is needed. Unfortunately, many neurological and psychiatric diseases impede certain cognitive abilities such as executive functioning or speed of processing; this can produce a poor fit between the patient and the cognitive demands of his or her environment. Such non-dementia diseases include bipolar disorder, schizophrenia, post-traumatic stress syndrome, depression, and anxiety disorders, just to name a few. Each of these diseases negatively affects particular areas of the brain, resulting in distinct cognitive profiles (e.g., deficits in executive functioning but normal speed of processing as seen in schizophrenia). In fact, it is from these cognitive deficits in which such behavioral and emotional symptoms may manifest (e.g., delusions, paranoia). This article highlights the distinct cognitive profiles of such common neurological and psychiatric diseases. An understanding of such disease-specific cognitive profiles can assist nurses in providing care to patients by knowing what cognitive deficits are associated with each disease and how these cognitive deficits impact everyday functioning and social interactions. Implications for nursing practice and research are posited within the framework of cognitive reserve and neuroplasticity. PMID:23422693

Authors' Response to "For Whom Is Argument and Explanation a Necessary Distinction? A Response to Osborne and Patterson" by Berland and McNeill

ERIC Educational Resources Information Center

Osborne, Jonathan; Patterson, Alexis

2012-01-01

In "For Whom Is Argument and Explanation a Necessary Distinction? A Response to Osborne and Patterson," Berland and McNeill seek to argue that there is an overlap between these two discourse acts such that, in the welter of classroom life, it is difficult to make the distinction. Indeed, in their article Jonathan Osborne and Alexis Patterson did…

Serum Cytokine Profiles Differentiating Hemorrhagic Fever with Renal Syndrome and Hantavirus Pulmonary Syndrome.

PubMed

Khaiboullina, Svetlana F; Levis, Silvana; Morzunov, Sergey P; Martynova, Ekaterina V; Anokhin, Vladimir A; Gusev, Oleg A; St Jeor, Stephen C; Lombardi, Vincent C; Rizvanov, Albert A

2017-01-01

Hantavirus infection is an acute zoonosis that clinically manifests in two primary forms, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is endemic in Europe and Russia, where the mild form of the disease is prevalent in the Tatarstan region. HPS is endemic in Argentina, as well as other countries of North and South American. HFRS and HPS are usually acquired via the upper respiratory tract by inhalation of virus-contaminated aerosol. Although the pathogenesis of HFRS and HPS remains largely unknown, postmortem tissue studies have identified endothelial cells as the primary target of infection. Importantly, cell damage due to virus replication, or subsequent tissue repair, has not been documented. Since no single factor has been identified that explains the complexity of HFRS or HPS pathogenesis, it has been suggested that a cytokine storm may play a crucial role in the manifestation of both diseases. In order to identify potential serological markers that distinguish HFRS and HPS, serum samples collected during early and late phases of the disease were analyzed for 48 analytes using multiplex magnetic bead-based assays. Overall, serum cytokine profiles associated with HPS revealed a more pro-inflammatory milieu as compared to HFRS. Furthermore, HPS was strictly characterized by the upregulation of cytokine levels, in contrast to HFRS where cases were distinguished by a dichotomy in serum cytokine levels. The severe form of hantavirus zoonosis, HPS, was characterized by the upregulation of a higher number of cytokines than HFRS (40 vs 21). In general, our analysis indicates that, although HPS and HFRS share many characteristic features, there are distinct cytokine profiles for these diseases. These profiles suggest a strong activation of an innate immune and inflammatory responses are associated with HPS, relative to HFRS, as well as a robust activation of Th1-type immune responses. Finally, the results of our analysis suggest that serum cytokines profiles of HPS and HFRS cases are consistent with the presence of extracellular matrix degradation, increased mononuclear leukocyte proliferation, and transendothelial migration.

Surface Glycosylation Profiles of Urine Extracellular Vesicles

PubMed Central

Gerlach, Jared Q.; Krüger, Anja; Gallogly, Susan; Hanley, Shirley A.; Hogan, Marie C.; Ward, Christopher J.

2013-01-01

Urinary extracellular vesicles (uEVs) are released by cells throughout the nephron and contain biomolecules from their cells of origin. Although uEV-associated proteins and RNA have been studied in detail, little information exists regarding uEV glycosylation characteristics. Surface glycosylation profiling by flow cytometry and lectin microarray was applied to uEVs enriched from urine of healthy adults by ultracentrifugation and centrifugal filtration. The carbohydrate specificity of lectin microarray profiles was confirmed by competitive sugar inhibition and carbohydrate-specific enzyme hydrolysis. Glycosylation profiles of uEVs and purified Tamm Horsfall protein were compared. In both flow cytometry and lectin microarray assays, uEVs demonstrated surface binding, at low to moderate intensities, of a broad range of lectins whether prepared by ultracentrifugation or centrifugal filtration. In general, ultracentrifugation-prepared uEVs demonstrated higher lectin binding intensities than centrifugal filtration-prepared uEVs consistent with lesser amounts of co-purified non-vesicular proteins. The surface glycosylation profiles of uEVs showed little inter-individual variation and were distinct from those of Tamm Horsfall protein, which bound a limited number of lectins. In a pilot study, lectin microarray was used to compare uEVs from individuals with autosomal dominant polycystic kidney disease to those of age-matched controls. The lectin microarray profiles of polycystic kidney disease and healthy uEVs showed differences in binding intensity of 6/43 lectins. Our results reveal a complex surface glycosylation profile of uEVs that is accessible to lectin-based analysis following multiple uEV enrichment techniques, is distinct from co-purified Tamm Horsfall protein and may demonstrate disease-specific modifications. PMID:24069349

African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks.

PubMed

Erkizan, Hayriye Verda; Johnson, Kory; Ghimbovschi, Svetlana; Karkera, Deepa; Trachiotis, Gregory; Adib, Houtan; Hoffman, Eric P; Wadleigh, Robert G

2017-06-19

Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), the subtype that shows marked variation in geographic frequency. The molecular architecture of African-American ESCC is still poorly understood. It is unclear why African-American ESCC is more aggressive and the survival rate in these patients is worse than those of other ethnic groups. To begin to define genetic alterations that occur in African-American ESCC we conducted microarray expression profiling in pairs of esophageal squamous cell tumors and matched control tissues. We found significant dysregulation of genes encoding drug-metabolizing enzymes and stress response components of the NRF2- mediated oxidative damage pathway, potentially representing key genes in African-American esophageal squamous carcinogenesis. Loss of activity of drug metabolizing enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence and aggressiveness of ESCC in this ethnic group. To determine whether certain genes are uniquely altered in African-American ESCC we performed a meta-analysis of ESCC expression profiles in our African-American samples and those of several Asian samples. Down-regulation of TP53 pathway components represented the most common feature in ESCC of all ethnic groups. Importantly, this analysis revealed a potential distinctive molecular underpinning of African-American ESCC, that is, a widespread and prominent involvement of the NRF2 pathway. Taken together, these findings highlight the remarkable interplay of genetic and environmental factors in the pathogenesis of African-American ESCC.

The Sterol Methyltransferases SMT1, SMT2, and SMT3 Influence Arabidopsis Development through Nonbrassinosteroid Products1[W][OA

PubMed Central

Carland, Francine; Fujioka, Shozo; Nelson, Timothy

2010-01-01

Plant sterols are structural components of cell membranes that provide rigidity, permeability, and regional identity to membranes. Sterols are also the precursors to the brassinosteroid signaling molecules. Evidence is accumulating that specific sterols have roles in pattern formation during development. COTYLEDON VASCULAR PATTERNING1 (CVP1) encodes C-24 STEROL METHYLTRANSFERASE2 (SMT2), one of three SMTs in Arabidopsis (Arabidopsis thaliana). SMT2 and SMT3, which also encodes a C-24 SMT, catalyze the reaction that distinguishes the synthesis of structural sterols from signaling brassinosteroid derivatives and are highly regulated. The deficiency of SMT2 in the cvp1 mutant results in moderate developmental defects, including aberrant cotyledon vein patterning, serrated floral organs, and reduced stature, but plants are viable, suggesting that SMT3 activity can substitute for the loss of SMT2. To test the distinct developmental roles of SMT2 and SMT3, we identified a transcript null smt3 mutant. Although smt3 single mutants appear wild type, cvp1 smt3 double mutants show enhanced defects relative to cvp1 mutants, such as discontinuous cotyledon vein pattern, and produce novel phenotypes, including defective root growth, loss of apical dominance, sterility, and homeotic floral transformations. These phenotypes are correlated with major alterations in the profiles of specific sterols but without significant alterations to brassinosteroid profiles. The alterations to sterol profiles in cvp1 mutants affect auxin response, demonstrated by weak auxin insensitivity, enhanced axr1 auxin resistance, ectopically expressed DR5:β-glucuronidase in developing embryos, and defective response to auxin-inhibited PIN2-green fluorescent protein endocytosis. We discuss the developmental roles of sterols implied by these results. PMID:20421456

Long-term fertilization determines different metabolomic profiles and responses in saplings of three rainforest tree species with different adult canopy position

PubMed Central

Gargallo-Garriga, Albert; Wright, S. Joseph; Sardans, Jordi; Pérez-Trujillo, Míriam; Oravec, Michal; Večeřová, Kristýna; Urban, Otmar; Fernández-Martínez, Marcos; Parella, Teodor; Peñuelas, Josep

2017-01-01

Background Tropical rainforests are frequently limited by soil nutrient availability. However, the response of the metabolic phenotypic plasticity of trees to an increase of soil nutrient availabilities is poorly understood. We expected that increases in the ability of a nutrient that limits some plant processes should be detected by corresponding changes in plant metabolome profile related to such processes. Methodology/Principal findings We studied the foliar metabolome of saplings of three abundant tree species in a 15 year field NPK fertilization experiment in a Panamanian rainforest. The largest differences were among species and explained 75% of overall metabolome variation. The saplings of the large canopy species, Tetragastris panamensis, had the lowest concentrations of all identified amino acids and the highest concentrations of most identified secondary compounds. The saplings of the “mid canopy” species, Alseis blackiana, had the highest concentrations of amino acids coming from the biosynthesis pathways of glycerate-3P, oxaloacetate and α-ketoglutarate, and the saplings of the low canopy species, Heisteria concinna, had the highest concentrations of amino acids coming from the pyruvate synthesis pathways. Conclusions/Significance The changes in metabolome provided strong evidence that different nutrients limit different species in different ways. With increasing P availability, the two canopy species shifted their metabolome towards larger investment in protection mechanisms, whereas with increasing N availability, the sub-canopy species increased its primary metabolism. The results highlighted the proportional distinct use of different nutrients by different species and the resulting different metabolome profiles in this high diversity community are consistent with the ecological niche theory. PMID:28493911

Deconvoluting Post-Transplant Immunity: Cell Subset-Specific Mapping Reveals Pathways for Activation and Expansion of Memory T, Monocytes and B Cells

PubMed Central

Grigoryev, Yevgeniy A.; Kurian, Sunil M.; Avnur, Zafi; Borie, Dominic; Deng, Jun; Campbell, Daniel; Sung, Joanna; Nikolcheva, Tania; Quinn, Anthony; Schulman, Howard; Peng, Stanford L.; Schaffer, Randolph; Fisher, Jonathan; Mondala, Tony; Head, Steven; Flechner, Stuart M.; Kantor, Aaron B.; Marsh, Christopher; Salomon, Daniel R.

2010-01-01

A major challenge for the field of transplantation is the lack of understanding of genomic and molecular drivers of early post-transplant immunity. The early immune response creates a complex milieu that determines the course of ensuing immune events and the ultimate outcome of the transplant. The objective of the current study was to mechanistically deconvolute the early immune response by purifying and profiling the constituent cell subsets of the peripheral blood. We employed genome-wide profiling of whole blood and purified CD4, CD8, B cells and monocytes in tandem with high-throughput laser-scanning cytometry in 10 kidney transplants sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. Cytometry confirmed early cell subset depletion by antibody induction and immunosuppression. Multiple markers revealed the activation and proliferative expansion of CD45RO+CD62L− effector memory CD4/CD8 T cells as well as progressive activation of monocytes and B cells. Next, we mechanistically deconvoluted early post-transplant immunity by serial monitoring of whole blood using DNA microarrays. Parallel analysis of cell subset-specific gene expression revealed a unique spectrum of time-dependent changes and functional pathways. Gene expression profiling results were validated with 157 different probesets matching all 65 antigens detected by cytometry. Thus, serial blood cell monitoring reflects the profound changes in blood cell composition and immune activation early post-transplant. Each cell subset reveals distinct pathways and functional programs. These changes illuminate a complex, early phase of immunity and inflammation that includes activation and proliferative expansion of the memory effector and regulatory cells that may determine the phenotype and outcome of the kidney transplant. PMID:20976225

Deconvoluting post-transplant immunity: cell subset-specific mapping reveals pathways for activation and expansion of memory T, monocytes and B cells.

PubMed

Grigoryev, Yevgeniy A; Kurian, Sunil M; Avnur, Zafi; Borie, Dominic; Deng, Jun; Campbell, Daniel; Sung, Joanna; Nikolcheva, Tania; Quinn, Anthony; Schulman, Howard; Peng, Stanford L; Schaffer, Randolph; Fisher, Jonathan; Mondala, Tony; Head, Steven; Flechner, Stuart M; Kantor, Aaron B; Marsh, Christopher; Salomon, Daniel R

2010-10-14

A major challenge for the field of transplantation is the lack of understanding of genomic and molecular drivers of early post-transplant immunity. The early immune response creates a complex milieu that determines the course of ensuing immune events and the ultimate outcome of the transplant. The objective of the current study was to mechanistically deconvolute the early immune response by purifying and profiling the constituent cell subsets of the peripheral blood. We employed genome-wide profiling of whole blood and purified CD4, CD8, B cells and monocytes in tandem with high-throughput laser-scanning cytometry in 10 kidney transplants sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. Cytometry confirmed early cell subset depletion by antibody induction and immunosuppression. Multiple markers revealed the activation and proliferative expansion of CD45RO(+)CD62L(-) effector memory CD4/CD8 T cells as well as progressive activation of monocytes and B cells. Next, we mechanistically deconvoluted early post-transplant immunity by serial monitoring of whole blood using DNA microarrays. Parallel analysis of cell subset-specific gene expression revealed a unique spectrum of time-dependent changes and functional pathways. Gene expression profiling results were validated with 157 different probesets matching all 65 antigens detected by cytometry. Thus, serial blood cell monitoring reflects the profound changes in blood cell composition and immune activation early post-transplant. Each cell subset reveals distinct pathways and functional programs. These changes illuminate a complex, early phase of immunity and inflammation that includes activation and proliferative expansion of the memory effector and regulatory cells that may determine the phenotype and outcome of the kidney transplant.

Simultaneous analysis of multiple T helper subsets in leprosy reveals distinct patterns of Th1, Th2, Th17 and Tregs markers expression in clinical forms and reactional events.

PubMed

Azevedo, Michelle de Campos Soriani; Marques, Heloisa; Binelli, Larissa Sarri; Malange, Mariana Silva Vieira; Devides, Amanda Carreira; Silva, Eliane Aparecida; Fachin, Luciana Raquel Vincenzi; Ghidella, Cassio Cesar; Soares, Cleverson Teixeira; Garlet, Gustavo Pompermaier; Rosa, Patrícia Sammarco; Belone, Andrea de Farias Fernandes; Trombone, Ana Paula Favaro

2017-12-01

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Previous studies have demonstrated that the difference among clinical forms of leprosy can be associated with the immune response of patients, mainly by T helper (Th) and regulatory T cells (Tregs). Then, aiming at clarifying the immune response, the expression of cytokines related to Th1, Th2, Th17 and Tregs profiles were evaluated by qPCR in 87 skin biopsies from leprosy patients. Additionally, cytokines and anti-PGL-1 antibodies were determined in serum by ELISA. The results showed that the expression of various targets (mRNA) related to Th1, Th2, Th17 and Tregs were significantly modulated in leprosy when compared with healthy individuals, suggesting the presence of a mixed profile. In addition, the targets related to Th1 predominated in the tuberculoid pole and side and Th2 and Tregs predominated in the lepromatous pole and side; however, Th17 targets showed a mixed profile. Concerning reactional events, Tregs markers were decreased and IL-15 was increased in reversal reaction and IL-17F, CCL20 and IL-8 in erythema nodosum leprosum, when compared with the respective non-reactional leprosy patients. Additionally, ELISA analysis demonstrated that IL-22, IL-6, IL-10 and anti-PGL-1 antibody levels were significantly higher in the serum of patients when compared with healthy individuals, and IL-10 and anti-PGL-1 antibodies were also increased in the lepromatous pole and side. Together, these results indicate that Th1, Th2 and Th17 are involved in the determination of clinical forms of leprosy and suggest that decreased Tregs activity may be involved in the pathogenesis of reactional events.

Gonadal development and transcript profiling of steroidogenic enzymes in response to 17α-methyltestosterone in the rare minnow Gobiocypris rarus.

PubMed

Liu, Shaozhen; Wang, Lihong; Qin, Fang; Zheng, Yao; Li, Meng; Zhang, Yingying; Yuan, Cong; Wang, Zaizhao

2014-09-01

It is well known that natural and anthropogenic chemicals interfere with the hormonal system of vertebrate and invertebrate organisms. How these chemicals regulate gonadal steroidogenesis remains to be determined. The main objective of this study was to evaluate the effects of 17α-methyltestosterone (MT), a synthetic model androgen, on gene expression profiles of six key steroidogenic genes in adult rare minnow. The full-length cDNA encoding 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) was firstly isolated and characterized by RT-PCR and RACE methods. The gonadal transcript changes of StAR, cyp11a1, 3β-HSD, cyp17a1, 11β-HSD2 and cyp19a1a in 6-month adult Gobiocypris rarus exposed to MT and 17α-ethinylestradiol (EE2) for 7, 14 and 21 days were detected by qRT-PCR. To make an effort to connect the transcriptional changes of steroidogenic enzymes with effects on higher levels of biological organization and on VTG, one remarkable sensitive target of steroids, body and gonad weights, histology of gonads, and hepatic vtg mRNA level were measured. MT caused varying degree of abnormalities in ovaries and testes. The hepatic vtg mRNA level was highly inhibited in females and slightly altered in males by MT. Transcripts of several steroidogenic genes including StAR, cyp17a1, and cyp11a1 showed high responsiveness to MT exposure in G. rarus. The gene expression profiles of these steroidogenic genes in MT-treated groups were much distinct with the EE2-treated group. Copyright © 2014 Elsevier Ltd. All rights reserved.