Genome-Wide RNAi Screen Identifies Broadly-Acting Host Factors That Inhibit Arbovirus Infection

PubMed Central

Yasunaga, Ari; Hanna, Sheri L.; Li, Jianqing; Cho, Hyelim; Rose, Patrick P.; Spiridigliozzi, Anna; Gold, Beth; Diamond, Michael S.; Cherry, Sara

2014-01-01

Vector-borne viruses are an important class of emerging and re-emerging pathogens; thus, an improved understanding of the cellular factors that modulate infection in their respective vertebrate and insect hosts may aid control efforts. In particular, cell-intrinsic antiviral pathways restrict vector-borne viruses including the type I interferon response in vertebrates and the RNA interference (RNAi) pathway in insects. However, it is likely that additional cell-intrinsic mechanisms exist to limit these viruses. Since insects rely on innate immune mechanisms to inhibit virus infections, we used Drosophila as a model insect to identify cellular factors that restrict West Nile virus (WNV), a flavivirus with a broad and expanding geographical host range. Our genome-wide RNAi screen identified 50 genes that inhibited WNV infection. Further screening revealed that 17 of these genes were antiviral against additional flaviviruses, and seven of these were antiviral against other vector-borne viruses, expanding our knowledge of invertebrate cell-intrinsic immunity. Investigation of two newly identified factors that restrict diverse viruses, dXPO1 and dRUVBL1, in the Tip60 complex, demonstrated they contributed to antiviral defense at the organismal level in adult flies, in mosquito cells, and in mammalian cells. These data suggest the existence of broadly acting and functionally conserved antiviral genes and pathways that restrict virus infections in evolutionarily divergent hosts. PMID:24550726

Identifying environmental variables explaining genotype-by-environment interaction for body weight of rainbow trout (Onchorynchus mykiss): reaction norm and factor analytic models.

PubMed

Sae-Lim, Panya; Komen, Hans; Kause, Antti; Mulder, Han A

2014-02-26

Identifying the relevant environmental variables that cause GxE interaction is often difficult when they cannot be experimentally manipulated. Two statistical approaches can be applied to address this question. When data on candidate environmental variables are available, GxE interaction can be quantified as a function of specific environmental variables using a reaction norm model. Alternatively, a factor analytic model can be used to identify the latent common factor that explains GxE interaction. This factor can be correlated with known environmental variables to identify those that are relevant. Previously, we reported a significant GxE interaction for body weight at harvest in rainbow trout reared on three continents. Here we explore their possible causes. Reaction norm and factor analytic models were used to identify which environmental variables (age at harvest, water temperature, oxygen, and photoperiod) may have caused the observed GxE interaction. Data on body weight at harvest was recorded on 8976 offspring reared in various locations: (1) a breeding environment in the USA (nucleus), (2) a recirculating aquaculture system in the Freshwater Institute in West Virginia, USA, (3) a high-altitude farm in Peru, and (4) a low-water temperature farm in Germany. Akaike and Bayesian information criteria were used to compare models. The combination of days to harvest multiplied with daily temperature (Day*Degree) and photoperiod were identified by the reaction norm model as the environmental variables responsible for the GxE interaction. The latent common factor that was identified by the factor analytic model showed the highest correlation with Day*Degree. Day*Degree and photoperiod were the environmental variables that differed most between Peru and other environments. Akaike and Bayesian information criteria indicated that the factor analytical model was more parsimonious than the reaction norm model. Day*Degree and photoperiod were identified as environmental

Identifying environmental variables explaining genotype-by-environment interaction for body weight of rainbow trout (Onchorynchus mykiss): reaction norm and factor analytic models

PubMed Central

2014-01-01

Background Identifying the relevant environmental variables that cause GxE interaction is often difficult when they cannot be experimentally manipulated. Two statistical approaches can be applied to address this question. When data on candidate environmental variables are available, GxE interaction can be quantified as a function of specific environmental variables using a reaction norm model. Alternatively, a factor analytic model can be used to identify the latent common factor that explains GxE interaction. This factor can be correlated with known environmental variables to identify those that are relevant. Previously, we reported a significant GxE interaction for body weight at harvest in rainbow trout reared on three continents. Here we explore their possible causes. Methods Reaction norm and factor analytic models were used to identify which environmental variables (age at harvest, water temperature, oxygen, and photoperiod) may have caused the observed GxE interaction. Data on body weight at harvest was recorded on 8976 offspring reared in various locations: (1) a breeding environment in the USA (nucleus), (2) a recirculating aquaculture system in the Freshwater Institute in West Virginia, USA, (3) a high-altitude farm in Peru, and (4) a low-water temperature farm in Germany. Akaike and Bayesian information criteria were used to compare models. Results The combination of days to harvest multiplied with daily temperature (Day*Degree) and photoperiod were identified by the reaction norm model as the environmental variables responsible for the GxE interaction. The latent common factor that was identified by the factor analytic model showed the highest correlation with Day*Degree. Day*Degree and photoperiod were the environmental variables that differed most between Peru and other environments. Akaike and Bayesian information criteria indicated that the factor analytical model was more parsimonious than the reaction norm model. Conclusions Day*Degree and

Genome-Wide Association Study of d-Amphetamine Response in Healthy Volunteers Identifies Putative Associations, Including Cadherin 13 (CDH13)

PubMed Central

Wardle, Margaret C.; Sokoloff, Greta; Stephens, Matthew; de Wit, Harriet; Palmer, Abraham A.

2012-01-01

Both the subjective response to d-amphetamine and the risk for amphetamine addiction are known to be heritable traits. Because subjective responses to drugs may predict drug addiction, identifying alleles that influence acute response may also provide insight into the genetic risk factors for drug abuse. We performed a Genome Wide Association Study (GWAS) for the subjective responses to amphetamine in 381 non-drug abusing healthy volunteers. Responses to amphetamine were measured using a double-blind, placebo-controlled, within-subjects design. We used sparse factor analysis to reduce the dimensionality of the data to ten factors. We identified several putative associations; the strongest was between a positive subjective drug-response factor and a SNP (rs3784943) in the 8th intron of cadherin 13 (CDH13; P = 4.58×10−8), a gene previously associated with a number of psychiatric traits including methamphetamine dependence. Additionally, we observed a putative association between a factor representing the degree of positive affect at baseline and a SNP (rs472402) in the 1st intron of steroid-5-alpha-reductase-α-polypeptide-1 (SRD5A1; P = 2.53×10−7), a gene whose protein product catalyzes the rate-limiting step in synthesis of the neurosteroid allopregnanolone. This SNP belongs to an LD-block that has been previously associated with the expression of SRD5A1 and differences in SRD5A1 enzymatic activity. The purpose of this study was to begin to explore the genetic basis of subjective responses to stimulant drugs using a GWAS approach in a modestly sized sample. Our approach provides a case study for analysis of high-dimensional intermediate pharmacogenomic phenotypes, which may be more tractable than clinical diagnoses. PMID:22952603

Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13).

PubMed

Hart, Amy B; Engelhardt, Barbara E; Wardle, Margaret C; Sokoloff, Greta; Stephens, Matthew; de Wit, Harriet; Palmer, Abraham A

2012-01-01

Both the subjective response to d-amphetamine and the risk for amphetamine addiction are known to be heritable traits. Because subjective responses to drugs may predict drug addiction, identifying alleles that influence acute response may also provide insight into the genetic risk factors for drug abuse. We performed a Genome Wide Association Study (GWAS) for the subjective responses to amphetamine in 381 non-drug abusing healthy volunteers. Responses to amphetamine were measured using a double-blind, placebo-controlled, within-subjects design. We used sparse factor analysis to reduce the dimensionality of the data to ten factors. We identified several putative associations; the strongest was between a positive subjective drug-response factor and a SNP (rs3784943) in the 8(th) intron of cadherin 13 (CDH13; P = 4.58×10(-8)), a gene previously associated with a number of psychiatric traits including methamphetamine dependence. Additionally, we observed a putative association between a factor representing the degree of positive affect at baseline and a SNP (rs472402) in the 1(st) intron of steroid-5-alpha-reductase-α-polypeptide-1 (SRD5A1; P = 2.53×10(-7)), a gene whose protein product catalyzes the rate-limiting step in synthesis of the neurosteroid allopregnanolone. This SNP belongs to an LD-block that has been previously associated with the expression of SRD5A1 and differences in SRD5A1 enzymatic activity. The purpose of this study was to begin to explore the genetic basis of subjective responses to stimulant drugs using a GWAS approach in a modestly sized sample. Our approach provides a case study for analysis of high-dimensional intermediate pharmacogenomic phenotypes, which may be more tractable than clinical diagnoses.

Factors influencing societal response of nanotechnology: an expert stakeholder analysis.

PubMed

Gupta, Nidhi; Fischer, Arnout R H; van der Lans, Ivo A; Frewer, Lynn J

2012-05-01

Nanotechnology can be described as an emerging technology and, as has been the case with other emerging technologies such as genetic modification, different socio-psychological factors will potentially influence societal responses to its development and application. These factors will play an important role in how nanotechnology is developed and commercialised. This article aims to identify expert opinion on factors influencing societal response to applications of nanotechnology. Structured interviews with experts on nanotechnology from North West Europe were conducted using repertory grid methodology in conjunction with generalized Procrustes analysis to examine the psychological constructs underlying societal uptake of 15 key applications of nanotechnology drawn from different areas (e.g. medicine, agriculture and environment, chemical, food, military, sports, and cosmetics). Based on expert judgement, the main factors influencing societal response to different applications of nanotechnology will be the extent to which applications are perceived to be beneficial, useful, and necessary, and how 'real' and physically close to the end-user these applications are perceived to be by the public. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11051-012-0857-x) contains supplementary material, which is available to authorized users.

Predation risk modifies behaviour by shaping the response of identified brain neurons.

PubMed

Magani, Fiorella; Luppi, Tomas; Nuñez, Jesus; Tomsic, Daniel

2016-04-15

Interpopulation comparisons in species that show behavioural variations associated with particular ecological disparities offer good opportunities for assessing how environmental factors may foster specific functional adaptations in the brain. Yet, studies on the neural substrate that can account for interpopulation behavioural adaptations are scarce. Predation is one of the strongest driving forces for behavioural evolvability and, consequently, for shaping structural and functional brain adaptations. We analysed the escape response of crabs ITALIC! Neohelice granulatafrom two isolated populations exposed to different risks of avian predation. Individuals from the high-risk area proved to be more reactive to visual danger stimuli (VDS) than those from an area where predators are rare. Control experiments indicate that the response difference was specific for impending visual threats. Subsequently, we analysed the response to VDS of a group of giant brain neurons that are thought to play a main role in the visually guided escape response of the crab. Neurons from animals of the population with the stronger escape response were more responsive to VDS than neurons from animals of the less reactive population. Our results suggest a robust linkage between the pressure imposed by the predation risk, the response of identified neurons and the behavioural outcome. © 2016. Published by The Company of Biologists Ltd.

Resveratrol regulates gene transcription via activation of stimulus-responsive transcription factors.

PubMed

Thiel, Gerald; Rössler, Oliver G

2017-03-01

Resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenolic phytoalexin of grapes and other fruits and plants, is a common constituent of our diet and of dietary supplements. Many health-promoting benefits have been connected with resveratrol in the treatment of cardiovascular diseases, cancer, diabetes, inflammation, neurodegeneration, and diseases connected with aging. To explain the pleiotropic effects of resveratrol, the molecular targets of this compound have to be identified on the cellular level. Resveratrol induces intracellular signal transduction pathways which ultimately lead to changes in the gene expression pattern of the cells. Here, we review the effect of resveratrol on the activation of the stimulus-responsive transcription factors CREB, AP-1, Egr-1, Elk-1, and Nrf2. Following activation, these transcription factors induce transcription of delayed response genes. The gene products of these delayed response genes are ultimately responsible for the changes in the biochemistry and physiology of resveratrol-treated cells. The activation of stimulus-responsive transcription factors may explain many of the intracellular activities of resveratrol. However, results obtained in vitro may not easily be transferred to in vivo systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

An audit to identify factors affecting response to treatment among depressed patients who have documented suicidal ideation/attempts in a Bedfordshire Community Mental Health Team.

PubMed

Holt, Clare; Agius, Mark; Butler, Sophie; Zaman, Rashid

2010-11-01

in recent years there has been a general move towards treating depressed patients in the community if at all possible. One factor that may reduce the likelihood of discharge from secondary care is suicidality (Butler et al. 2010). The aim of this audit was to identify factors associated with continued suicidality among patients in a CMHT. we searched an anonymised database of patients and identified all those with previously documented suicidal thoughts or attempts. We also noted the presence of factors such as alcohol problems, drug problems, augmentation therapy and 'other risk' factors (e.g. financial problems or homelessness). We then looked at clinical notes to find out whether or not, according to the latest clinic letter, patients were still reporting suicidality. This facilitated comparison of the aforementioned factors between the group of patients in which suicidality was still present (group N) and the group of patients in which suicidality was no longer a feature (group Y). of the 56 patients with suicidal thoughts or attempts there were 44 in group N (79%) and 12 in group Y (21%). Overall, alcohol problems, drug problems and 'other' risk factors were proportionally more common among group Y than group N, although sometimes the difference was marginal. Conversely, the percentage of patients on augmentation therapy was greater in group N than group Y. When considering individual diagnostic categories the above trends generally stood for the F32 category, although not necessarily for the F33 category. the audit provides an insight into the sorts of factors that might influence outcomes among depressed patients. However, there are limitations to the audit such as small sample size and lack of a fixed follow-up period. Although the results are suggestive, it is difficult to make firm conclusions about patient outcomes on the basis of this data. The audit provides a useful starting point, especially in considering the treatment of patients within the BECMHT

Attainment Gap and Responsible Factors: A Quantitative Study in Secondary Schools in Cyprus

ERIC Educational Resources Information Center

Theodosiou-Zipiti, Galatia; Lamprianou, Iasonas; West, Mel; Muijs, Daniel

2011-01-01

The population in Cyprus, a recent European Union member, has become much more heterogeneous during the past decade. Here, we examine the attainment patterns of minority and native students enrolled in six secondary schools from different cities in Cyprus, and identify factors responsible for these patterns. The combination of examined factors has…

Bombyx mori Transcription Factors: Genome-Wide Identification, Expression Profiles and Response to Pathogens by Microarray Analysis

PubMed Central

Huang, Lulin; Cheng, Tingcai; Xu, Pingzhen; Fang, Ting; Xia, Qingyou

2012-01-01

Transcription factors are present in all living organisms, and play vital roles in a wide range of biological processes. Studies of transcription factors will help reveal the complex regulation mechanism of organisms. So far, hundreds of domains have been identified that show transcription factor activity. Here, 281 reported transcription factor domains were used as seeds to search the transcription factors in genomes of Bombyx mori L. (Lepidoptera: Bombycidae) and four other model insects. Overall, 666 transcription factors including 36 basal factors and 630 other factors were identified in B. mori genome, which accounted for 4.56% of its genome. The silkworm transcription factors' expression profiles were investigated in relation to multiple tissues, developmental stages, sexual dimorphism, and responses to oral infection by pathogens and direct bacterial injection. These all provided rich clues for revealing the transcriptional regulation mechanism of silkworm organ differentiation, growth and development, sexual dimorphism, and response to pathogen infection. PMID:22943524

Integrated analysis of rice transcriptomic and metabolomic responses to elevated night temperatures identifies sensitivity- and tolerance-related profiles.

PubMed

Glaubitz, Ulrike; Li, Xia; Schaedel, Sandra; Erban, Alexander; Sulpice, Ronan; Kopka, Joachim; Hincha, Dirk K; Zuther, Ellen

2017-01-01

Transcript and metabolite profiling were performed on leaves from six rice cultivars under high night temperature (HNT) condition. Six genes were identified as central for HNT response encoding proteins involved in transcription regulation, signal transduction, protein-protein interactions, jasmonate response and the biosynthesis of secondary metabolites. Sensitive cultivars showed specific changes in transcript abundance including abiotic stress responses, changes of cell wall-related genes, of ABA signaling and secondary metabolism. Additionally, metabolite profiles revealed a highly activated TCA cycle under HNT and concomitantly increased levels in pathways branching off that could be corroborated by enzyme activity measurements. Integrated data analysis using clustering based on one-dimensional self-organizing maps identified two profiles highly correlated with HNT sensitivity. The sensitivity profile included genes of the functional bins abiotic stress, hormone metabolism, cell wall, signaling, redox state, transcription factors, secondary metabolites and defence genes. In the tolerance profile, similar bins were affected with slight differences in hormone metabolism and transcription factor responses. Metabolites of the two profiles revealed involvement of GABA signaling, thus providing a link to the TCA cycle status in sensitive cultivars and of myo-inositol as precursor for inositol phosphates linking jasmonate signaling to the HNT response specifically in tolerant cultivars. © 2016 John Wiley & Sons Ltd.

Using clinical vignettes to assess doctors' and medical students' ability to identify sociocultural factors affecting health and health care.

PubMed

Hudelson, Patricia; Perron, N Junod; Perneger, Thomas

2011-01-01

Methods are needed for assessing clinicians' cultural knowledge frameworks. We used a mail survey containing four short clinical vignettes to explore respondents' ability to identify sociocultural factors affecting health and health care. Participants included 299 physicians working at the University Hospitals of Geneva, 156 private physicians, and all 134 local medical students in their clinical years. Twenty-one sociocultural "domains" were identified through inductive coding of responses. For each vignette, we obtained the sum of codes as a measure of the respondent's awareness of sociocultural factors that might affect care in this particular situation. As internal consistency was reasonably high (0.68), we computed a single total score as the sum of responses given to all four vignettes. Reponses correlated with factors that might be expected to impact clinicians' awareness of sociocultural factors affecting care. Medical students, females, respondents who had received cultural competence training, those with greater interest in caring for immigrant patients, and those with high self-assessed skills at exploring psychosocial and migration-related issues scored higher on the vignettes. Brief clinical vignettes appear to be a relevant and feasible method for exploring physicians' knowledge of social and cultural factors affecting health and health care.

Basic Fibroblast Growth Factor Activates Serum Response Factor Gene Expression by Multiple Distinct Signaling Mechanisms

PubMed Central

Spencer, Jeffrey A.; Major, Michael L.; Misra, Ravi P.

1999-01-01

Serum response factor (SRF) plays a central role in the transcriptional response of mammalian cells to a variety of extracellular signals. It is a key regulator of many cellular early response genes which are believed to be involved in cell growth and differentiation. The mechanism by which SRF activates transcription in response to mitogenic agents has been extensively studied; however, significantly less is known about regulation of the SRF gene itself. Previously, we identified distinct regulatory elements in the SRF promoter that play a role in activation, including a consensus ETS domain binding site, a consensus overlapping Sp/Egr-1 binding site, and two SRF binding sites. We further showed that serum induces SRF by a mechanism that requires an intact SRF binding site, also termed a CArG box. In the present study we demonstrate that in response to stimulation of cells by a purified growth factor, basic fibroblast growth factor (bFGF), the SRF promoter is upregulated by a complex pathway that involves at least two independent mechanisms: a CArG box-independent mechanism that is mediated by an ETS binding site, and a novel CArG box-dependent mechanism that requires both an Sp factor binding site and the CArG motifs for maximal stimulation. Our analysis indicates that the CArG/Sp element activation mechanism is mediated by distinct signaling pathways. The CArG box-dependent component is targeted by a Rho-mediated pathway, and the Sp binding site-dependent component is targeted by a Ras-mediated pathway. Both SRF and bFGF have been implicated in playing an important role in mediating cardiogenesis during development. The implications of our findings for SRF expression during development are discussed. PMID:10330138

Identifying factors which enhance capacity to engage in clinical education among podiatry practitioners: an action research project.

PubMed

Abey, Sally; Lea, Susan; Callaghan, Lynne; Shaw, Steve; Cotton, Debbie

2015-01-01

Health profession students develop practical skills whilst integrating theory with practice in a real world environment as an important component of their training. Research in the area of practice placements has identified challenges and barriers to the delivery of effective placement learning. However, there has been little research in podiatry and the question of which factors impact upon clinical educators' capacity to engage with the role remains an under-researched area. This paper presents the second phase of an action research project designed to determine the factors that impact upon clinical educators' capacity to engage with the mentorship role. An online survey was developed and podiatry clinical educators recruited through National Health Service (NHS) Trusts. The survey included socio-demographic items, and questions relating to the factors identified as possible variables influencing clinical educator capacity; the latter was assessed using the 'Clinical Educator Capacity to Engage' scale (CECE). Descriptive statistics were used to explore demographic data whilst the relationship between the CECE and socio-demographic factors were examined using inferential statistics in relation to academic profile, career profile and organisation of the placement. The survey response rate was 42 % (n = 66). Multiple linear regression identified four independent variables which explain a significant proportion of the variability of the dependent variable, 'capacity to engage with clinical education', with an adjusted R2 of 0.428. The four variables were: protected mentorship time, clinical educator relationship with university, sign-off responsibility, and volunteer status. The identification of factors that impact upon clinical educators' capacity to engage in mentoring of students has relevance for strategic planning and policy-making with the emphasis upon capacity-building at an individual level, so that the key attitudes and characteristics that are linked

Familial factors responsible for persistent crying-induced asthma: a case report.

PubMed

Weinstein, A G

1987-10-01

Crying behavior of the asthmatic child may induce wheezing symptoms. This may be a clinical problem for families with asthmatic children who exhibit frequent and persistent crying behavior. This case report identifies behaviors by the child and parents that may be responsible for continual crying. Child factors include (1) "spoiled" personality, (2) poor self-image, (3) biologic sensitivity to foods, medication, and environmental allergens producing irritability. Parental factors include poor disciplinary practices secondary to (1) disrupted home life, (2) guilt, and (3) overprotective behavior. Identification of these factors may be helpful in establishing clinical management strategies to reduce crying-induced asthma.

Test-retest reliability of the underlying latent factor structure of alcohol subjective response.

PubMed

Lutz, Joseph A; Childs, Emma

2017-04-01

Alcohol subjective experiences are multi-dimensional and demonstrate wide inter-individual variability. Recent efforts have sought to establish a clearer understanding of subjective alcohol responses by identifying core constructs derived from multiple measurement instruments. The aim of this study was to evaluate the temporal stability of this approach to conceptualizing alcohol subjective experiences across successive alcohol administrations in the same individuals. Healthy moderate alcohol drinkers (n = 104) completed six experimental sessions each, three with alcohol (0.8 g/kg), and three with a non-alcoholic control beverage. Participants reported subjective mood and drug effects using standardized questionnaires before and at repeated times after beverage consumption. We explored the underlying latent structure of subjective responses for all alcohol administrations using exploratory factor analysis and then tested measurement invariance over the three successive administrations using multi-group confirmatory factor analyses. Exploratory factor analyses on responses to alcohol across all administrations yielded four factors representing "Positive mood," "Sedation," "Stimulation/Euphoria," and "Drug effects and Urges." A confirmatory factor analysis on the separate administrations indicated acceptable configural and metric invariance and moderate scalar invariance. In this study, we demonstrate temporal stability of the underlying constructs of subjective alcohol responses derived from factor analysis. These findings strengthen the utility of this approach to conceptualizing subjective alcohol responses especially for use in prospective and longitudinal alcohol challenge studies relating subjective response to alcohol use disorder risk.

Jasmonate-responsive transcription factors regulating plant secondary metabolism.

PubMed

Zhou, Meiliang; Memelink, Johan

2016-01-01

Plants produce a large variety of secondary metabolites including alkaloids, glucosinolates, terpenoids and phenylpropanoids. These compounds play key roles in plant-environment interactions and many of them have pharmacological activity in humans. Jasmonates (JAs) are plant hormones which induce biosynthesis of many secondary metabolites. JAs-responsive transcription factors (TFs) that regulate the JAs-induced accumulation of secondary metabolites belong to different families including AP2/ERF, bHLH, MYB and WRKY. Here, we give an overview of the types and functions of TFs that have been identified in JAs-induced secondary metabolite biosynthesis, and highlight their similarities and differences in regulating various biosynthetic pathways. We review major recent developments regarding JAs-responsive TFs mediating secondary metabolite biosynthesis, and provide suggestions for further studies. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel transcription factor gene FHS1 is involved in the DNA damage response in Fusarium graminearum

PubMed Central

Son, Hokyoung; Fu, Minmin; Lee, Yoonji; Lim, Jae Yun; Min, Kyunghun; Kim, Jin-Cheol; Choi, Gyung Ja; Lee, Yin-Won

2016-01-01

Cell cycle regulation and the maintenance of genome integrity are crucial for the development and virulence of the pathogenic plant fungus Fusarium graminearum. To identify transcription factors (TFs) related to these processes, four DNA-damaging agents were applied to screen a F. graminearum TF mutant library. Sixteen TFs were identified to be likely involved in DNA damage responses. Fhs1 is a fungal specific Zn(II)2Cys6 TF that localises exclusively to nuclei. fhs1 deletion mutants were hypersensitive to hydroxyurea and defective in mitotic cell division. Moreover, deletion of FHS1 resulted in defects in perithecia production and virulence and led to the accumulation of DNA damage. Our genetic evidence demonstrated that the FHS1-associated signalling pathway for DNA damage response is independent of the ATM or ATR pathways. This study identified sixteen genes involved in the DNA damage response and is the first to characterise the novel transcription factor gene FHS1, which is involved in the DNA damage response. The results provide new insights into mechanisms underlying DNA damage responses in fungi, including F. graminearum. PMID:26888604

Two soybean bHLH factors regulate response to iron deficiency.

PubMed

Li, Lin; Gao, Wenwen; Peng, Qi; Zhou, Bin; Kong, Qihui; Ying, Yinghui; Shou, Huixia

2018-03-25

Iron is an indispensable micronutrient for plant growth and development. Limited bioavailability of Fe in the soil leads to iron deficiency chlorosis in plants and yield loss. In this study, two soybean basic helix-loop-helix transcription factors, GmbHLH57 and GmbHLH300, were identified in response to Fe-deficiency. Both transcription factors are expressed in roots and nodules, and are induced by Fe deficiency; these patterns were confirmed in transgenic hairy roots expressing constructs of the endogenous promoters fused to a GUS reporter gene. Bimolecular fluorescence complementation, yeast two-hybrid and coimmunoprecipitation (co-IP) assays indicated a physical interaction between GmbHLH57 and GmbHLH300. Studies on transgenic soybeans overexpressing GmbHLH57 and GmbHLH300 revealed that overexpression of each transcription factor, alone, results in no change of the responses to Fe deficiency, whereas overexpression of both transcription factors upregulated the downstream Fe uptake genes and increased the Fe content in these transgenic plants. Compared to wild type, these double overexpression transgenic plants were more tolerant to Fe deficiency. Taken together, our findings establish that GmbHLH57 and GmbHLH300 are important transcription factors involved in Fe homeostasis in soybean. © 2018 Institute of Botany, Chinese Academy of Sciences.

A serum response factor-dependent transcriptional regulatory program identifies distinct smooth muscle cell sublineages.

PubMed Central

Kim, S; Ip, H S; Lu, M M; Clendenin, C; Parmacek, M S

1997-01-01

The SM22alpha promoter has been used as a model system to define the molecular mechanisms that regulate smooth muscle cell (SMC) specific gene expression during mammalian development. The SM22alpha gene is expressed exclusively in vascular and visceral SMCs during postnatal development and is transiently expressed in the heart and somites during embryogenesis. Analysis of the SM22alpha promoter in transgenic mice revealed that 280 bp of 5' flanking sequence is sufficient to restrict expression of the lacZ reporter gene to arterial SMCs and the myotomal component of the somites. DNase I footprint and electrophoretic mobility shift analyses revealed that the SM22alpha promoter contains six nuclear protein binding sites (designated smooth muscle elements [SMEs] -1 to -6, respectively), two of which bind serum response factor (SRF) (SME-1 and SME-4). Mutational analyses demonstrated that a two-nucleotide substitution that selectively eliminates SRF binding to SME-4 decreases SM22alpha promoter activity in arterial SMCs by approximately 90%. Moreover, mutations that abolish binding of SRF to SME-1 and SME-4 or mutations that eliminate each SME-3 binding activity totally abolished SM22alpha promoter activity in the arterial SMCs and somites of transgenic mice. Finally, we have shown that a multimerized copy of SME-4 (bp -190 to -110) when linked to the minimal SM22alpha promoter (bp -90 to +41) is necessary and sufficient to direct high-level transcription in an SMC lineage-restricted fashion. Taken together, these data demonstrate that distinct transcriptional regulatory programs control SM22alpha gene expression in arterial versus visceral SMCs. Moreover, these data are consistent with a model in which combinatorial interactions between SRF and other transcription factors that bind to SME-4 (and that bind directly to SRF) activate transcription of the SM22alpha gene in arterial SMCs. PMID:9121477

Identifying influential factors of business process performance using dependency analysis

NASA Astrophysics Data System (ADS)

Wetzstein, Branimir; Leitner, Philipp; Rosenberg, Florian; Dustdar, Schahram; Leymann, Frank

2011-02-01

We present a comprehensive framework for identifying influential factors of business process performance. In particular, our approach combines monitoring of process events and Quality of Service (QoS) measurements with dependency analysis to effectively identify influential factors. The framework uses data mining techniques to construct tree structures to represent dependencies of a key performance indicator (KPI) on process and QoS metrics. These dependency trees allow business analysts to determine how process KPIs depend on lower-level process metrics and QoS characteristics of the IT infrastructure. The structure of the dependencies enables a drill-down analysis of single factors of influence to gain a deeper knowledge why certain KPI targets are not met.

Consumer factors predicting level of treatment response to illness management and recovery.

PubMed

White, Dominique A; McGuire, Alan B; Luther, Lauren; Anderson, Adrienne I; Phalen, Peter; McGrew, John H

2017-12-01

This study aims to identify consumer-level predictors of level of treatment response to illness management and recovery (IMR) to target the appropriate consumers and aid psychiatric rehabilitation settings in developing intervention adaptations. Secondary analyses from a multisite study of IMR were conducted. Self-report data from consumer participants of the parent study (n = 236) were analyzed for the current study. Consumers completed prepost surveys assessing illness management, coping, goal-related hope, social support, medication adherence, and working alliance. Correlations and multiple regression analyses were run to identify self-report variables that predicted level of treatment response to IMR. Analyses revealed that goal-related hope significantly predicted level of improved illness self-management, F(1, 164) = 10.93, p < .001, R2 = .248, R2 change = .05. Additionally, we found that higher levels of maladaptive coping at baseline were predictive of higher levels of adaptive coping at follow-up, F(2, 180) = 5.29, p < .02, R2 = .38, R2 change = .02. Evidence did not support additional predictors. Previously, consumer-level predictors of level of treatment response have not been explored for IMR. Although 2 significant predictors were identified, study findings suggest more work is needed. Future research is needed to identify additional consumer-level factors predictive of IMR treatment response in order to identify who would benefit most from this treatment program. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Transcription Factor Arabidopsis Activating Factor1 Integrates Carbon Starvation Responses with Trehalose Metabolism1[OPEN

PubMed Central

Garapati, Prashanth; Feil, Regina; Lunn, John Edward; Van Dijck, Patrick; Balazadeh, Salma; Mueller-Roeber, Bernd

2015-01-01

Plants respond to low carbon supply by massive reprogramming of the transcriptome and metabolome. We show here that the carbon starvation-induced NAC (for NO APICAL MERISTEM/ARABIDOPSIS TRANSCRIPTION ACTIVATION FACTOR/CUP-SHAPED COTYLEDON) transcription factor Arabidopsis (Arabidopsis thaliana) Transcription Activation Factor1 (ATAF1) plays an important role in this physiological process. We identified TREHALASE1, the only trehalase-encoding gene in Arabidopsis, as a direct downstream target of ATAF1. Overexpression of ATAF1 activates TREHALASE1 expression and leads to reduced trehalose-6-phosphate levels and a sugar starvation metabolome. In accordance with changes in expression of starch biosynthesis- and breakdown-related genes, starch levels are generally reduced in ATAF1 overexpressors but elevated in ataf1 knockout plants. At the global transcriptome level, genes affected by ATAF1 are broadly associated with energy and carbon starvation responses. Furthermore, transcriptional responses triggered by ATAF1 largely overlap with expression patterns observed in plants starved for carbon or energy supply. Collectively, our data highlight the existence of a positively acting feedforward loop between ATAF1 expression, which is induced by carbon starvation, and the depletion of cellular carbon/energy pools that is triggered by the transcriptional regulation of downstream gene regulatory networks by ATAF1. PMID:26149570

Identifying Causal Risk Factors for Violence among Discharged Patients

PubMed Central

Coid, Jeremy W.; Kallis, Constantinos; Doyle, Mike; Shaw, Jenny; Ullrich, Simone

2015-01-01

Background Structured Professional Judgement (SPJ) is routinely administered in mental health and criminal justice settings but cannot identify violence risk above moderate accuracy. There is no current evidence that violence can be prevented using SPJ. This may be explained by routine application of predictive instead of causal statistical models when standardising SPJ instruments. Methods We carried out a prospective cohort study of 409 male and female patients discharged from medium secure services in England and Wales to the community. Measures were taken at baseline (pre-discharge), 6 and 12 months post-discharge using the Historical, Clinical and Risk-20 items version 3 (HCR-20v3) and Structural Assessment of Protective Factors (SAPROF). Information on violence was obtained via the McArthur community violence instrument and the Police National Computer. Results In a lagged model, HCR-20v3 and SAPROF items were poor predictors of violence. Eight items of the HCR-20v3 and 4 SAPROF items did not predict violent behaviour better than chance. In re-analyses considering temporal proximity of risk/ protective factors (exposure) on violence (outcome), risk was elevated due to violent ideation (OR 6.98, 95% CI 13.85–12.65, P<0.001), instability (OR 5.41, 95% CI 3.44–8.50, P<0.001), and poor coping/ stress (OR 8.35, 95% CI 4.21–16.57, P<0.001). All 3 risk factors were explanatory variables which drove the association with violent outcome. Self-control (OR 0.13, 95% CI 0.08–0.24, P<0.001) conveyed protective effects and explained the association of other protective factors with violence. Conclusions Using two standardised SPJ instruments, predictive (lagged) methods could not identify risk and protective factors which must be targeted in interventions for discharged patients with severe mental illness. Predictive methods should be abandoned if the aim is to progress from risk assessment to effective risk management and replaced by methods which identify factors

A Quantitative Assessment of the Factors that Influence Technology Acceptance in Emergency Response

ERIC Educational Resources Information Center

Seiter, Thomas C.

2012-01-01

Traditional models for studying user acceptance and adoption of technology focused on the factors that identify and tested the relationships forged between the user and the technology in question. In emergency response, implementing technology without user acceptance may affect the safety of the responders and citizenry. Integrating the factors…

Using factor analysis to identify neuromuscular synergies during treadmill walking

NASA Technical Reports Server (NTRS)

Merkle, L. A.; Layne, C. S.; Bloomberg, J. J.; Zhang, J. J.

1998-01-01

Neuroscientists are often interested in grouping variables to facilitate understanding of a particular phenomenon. Factor analysis is a powerful statistical technique that groups variables into conceptually meaningful clusters, but remains underutilized by neuroscience researchers presumably due to its complicated concepts and procedures. This paper illustrates an application of factor analysis to identify coordinated patterns of whole-body muscle activation during treadmill walking. Ten male subjects walked on a treadmill (6.4 km/h) for 20 s during which surface electromyographic (EMG) activity was obtained from the left side sternocleidomastoid, neck extensors, erector spinae, and right side biceps femoris, rectus femoris, tibialis anterior, and medial gastrocnemius. Factor analysis revealed 65% of the variance of seven muscles sampled aligned with two orthogonal factors, labeled 'transition control' and 'loading'. These two factors describe coordinated patterns of muscular activity across body segments that would not be evident by evaluating individual muscle patterns. The results show that factor analysis can be effectively used to explore relationships among muscle patterns across all body segments to increase understanding of the complex coordination necessary for smooth and efficient locomotion. We encourage neuroscientists to consider using factor analysis to identify coordinated patterns of neuromuscular activation that would be obscured using more traditional EMG analyses.

Identifying molecular subtypes related to clinicopathologic factors in pancreatic cancer

PubMed Central

2014-01-01

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors and usually presented with locally advanced and distant metastasis disease, which prevent curative resection or treatments. In this regard, we considered identifying molecular subtypes associated with clinicopathological factor as prognosis factors to stratify PDAC for appropriate treatment of patients. Results In this study, we identified three molecular subtypes which were significant on survival time and metastasis. We also identified significant genes and enriched pathways represented for each molecular subtype. Considering R0 resection patients included in each subtype, metastasis and survival times are significantly associated with subtype 1 and subtype 2. Conclusions We observed three PDAC molecular subtypes and demonstrated that those subtypes were significantly related with metastasis and survival time. The study may have utility in stratifying patients for cancer treatment. PMID:25560450

Identifying drought response of semi-arid aeolian systems using near-surface luminescence profiles and changepoint analysis, Nebraska Sandhills.

NASA Astrophysics Data System (ADS)

Buckland, Catherine; Bailey, Richard; Thomas, David

2017-04-01

Two billion people living in drylands are affected by land degradation. Sediment erosion by wind and water removes fertile soil and destabilises landscapes. Vegetation disturbance is a key driver of dryland erosion caused by both natural and human forcings: drought, fire, land use, grazing pressure. A quantified understanding of vegetation cover sensitivities and resultant surface change to forcing factors is needed if the vegetation and landscape response to future climate change and human pressure are to be better predicted. Using quartz luminescence dating and statistical changepoint analysis (Killick & Eckley, 2014) this study demonstrates the ability to identify step-changes in depositional age of near-surface sediments. Lx/Tx luminescence profiles coupled with statistical analysis show the use of near-surface sediments in providing a high-resolution record of recent system response and aeolian system thresholds. This research determines how the environment has recorded and retained sedimentary evidence of drought response and land use disturbances over the last two hundred years across both individual landforms and the wider Nebraska Sandhills. Identifying surface deposition and comparing with records of climate, fire and land use changes allows us to assess the sensitivity and stability of the surface sediment to a range of forcing factors. Killick, R and Eckley, IA. (2014) "changepoint: An R Package for Changepoint Analysis." Journal of Statistical Software, (58) 1-19.

Diversity Outbred Mice Identify Population-Based Exposure Thresholds and Genetic Factors that Influence Benzene-Induced Genotoxicity

PubMed Central

Gatti, Daniel M.; Morgan, Daniel L.; Kissling, Grace E.; Shockley, Keith R.; Knudsen, Gabriel A.; Shepard, Kim G.; Price, Herman C.; King, Deborah; Witt, Kristine L.; Pedersen, Lars C.; Munger, Steven C.; Svenson, Karen L.; Churchill, Gary A.

2014-01-01

Background Inhalation of benzene at levels below the current exposure limit values leads to hematotoxicity in occupationally exposed workers. Objective We sought to evaluate Diversity Outbred (DO) mice as a tool for exposure threshold assessment and to identify genetic factors that influence benzene-induced genotoxicity. Methods We exposed male DO mice to benzene (0, 1, 10, or 100 ppm; 75 mice/exposure group) via inhalation for 28 days (6 hr/day for 5 days/week). The study was repeated using two independent cohorts of 300 animals each. We measured micronuclei frequency in reticulocytes from peripheral blood and bone marrow and applied benchmark concentration modeling to estimate exposure thresholds. We genotyped the mice and performed linkage analysis. Results We observed a dose-dependent increase in benzene-induced chromosomal damage and estimated a benchmark concentration limit of 0.205 ppm benzene using DO mice. This estimate is an order of magnitude below the value estimated using B6C3F1 mice. We identified a locus on Chr 10 (31.87 Mb) that contained a pair of overexpressed sulfotransferases that were inversely correlated with genotoxicity. Conclusions The genetically diverse DO mice provided a reproducible response to benzene exposure. The DO mice display interindividual variation in toxicity response and, as such, may more accurately reflect the range of response that is observed in human populations. Studies using DO mice can localize genetic associations with high precision. The identification of sulfotransferases as candidate genes suggests that DO mice may provide additional insight into benzene-induced genotoxicity. Citation French JE, Gatti DM, Morgan DL, Kissling GE, Shockley KR, Knudsen GA, Shepard KG, Price HC, King D, Witt KL, Pedersen LC, Munger SC, Svenson KL, Churchill GA. 2015. Diversity Outbred mice identify population-based exposure thresholds and genetic factors that influence benzene-induced genotoxicity. Environ Health Perspect 123:237�

A systems biology perspective on the role of WRKY transcription factors in drought responses in plants.

PubMed

Tripathi, Prateek; Rabara, Roel C; Rushton, Paul J

2014-02-01

Drought is one of the major challenges affecting crop productivity and yield. However, water stress responses are notoriously multigenic and quantitative with strong environmental effects on phenotypes. It is also clear that water stress often does not occur alone under field conditions but rather in conjunction with other abiotic stresses such as high temperature and high light intensities. A multidisciplinary approach with successful integration of a whole range of -omics technologies will not only define the system, but also provide new gene targets for both transgenic approaches and marker-assisted selection. Transcription factors are major players in water stress signaling and some constitute major hubs in the signaling webs. The main transcription factors in this network include MYB, bHLH, bZIP, ERF, NAC, and WRKY transcription factors. The role of WRKY transcription factors in abiotic stress signaling networks is just becoming apparent and systems biology approaches are starting to define their places in the signaling network. Using systems biology approaches, there are now many transcriptomic analyses and promoter analyses that concern WRKY transcription factors. In addition, reports on nuclear proteomics have identified WRKY proteins that are up-regulated at the protein level by water stress. Interactomics has started to identify different classes of WRKY-interacting proteins. What are often lacking are connections between metabolomics, WRKY transcription factors, promoters, biosynthetic pathways, fluxes and downstream responses. As more levels of the system are characterized, a more detailed understanding of the roles of WRKY transcription factors in drought responses in crops will be obtained.

Identifying the challenging factors in the transition from colleges of engineering to employment

NASA Astrophysics Data System (ADS)

Baytiyeh, Hoda; Naja, Mohamad

2012-03-01

The transition from university to a career in engineering is a challenging process. This study examined the perceptions of engineering graduates regarding the difficulties they encountered in their transition from the university to the workplace. Lebanese practising engineers (n=217), living around the world, were surveyed to identify their current employment situations and their attitudes toward their academic preparation. Factor analysis revealed three main challenges facing engineering graduates: communication; responsibility; self-confidence. Seventeen interviews were conducted to gather information on ways to facilitate this transition. Comments reflected the need for better collaboration between engineering schools and engineering firms. The results will provide insight for engineering colleges, faculty members and administrators into the challenges faced by graduates and their aspirations for a smoother transition into employment.

Comprehensive Profiling of Ethylene Response Factor Expression Identifies Ripening-Associated ERF Genes and Their Link to Key Regulators of Fruit Ripening in Tomato1[OPEN

PubMed Central

Gomes, Bruna Lima; Mila, Isabelle; Frasse, Pierre; Zouine, Mohamed; Bouzayen, Mondher

2016-01-01

Our knowledge of the factors mediating ethylene-dependent ripening of climacteric fruit remains limited. The transcription of ethylene-regulated genes is mediated by ethylene response factors (ERFs), but mutants providing information on the specific role of the ERFs in fruit ripening are still lacking, likely due to functional redundancy among this large multigene family of transcription factors. We present here a comprehensive expression profiling of tomato (Solanum lycopersicum) ERFs in wild-type and tomato ripening-impaired tomato mutants (Never-ripe [Nr], ripening-inhibitor [rin], and non-ripening [nor]), indicating that out of the 77 ERFs present in the tomato genome, 27 show enhanced expression at the onset of ripening while 28 display a ripening-associated decrease in expression, suggesting that different ERFs may have contrasting roles in fruit ripening. Among the 19 ERFs exhibiting the most consistent up-regulation during ripening, the expression of 11 ERFs is strongly down-regulated in rin, nor, and Nr tomato ripening mutants, while only three are consistently up-regulated. Members of subclass E, SlERF.E1, SlERF.E2, and SlERF.E4, show dramatic down-regulation in the ripening mutants, suggesting that their expression might be instrumental in fruit ripening. This study illustrates the high complexity of the regulatory network connecting RIN and ERFs and identifies subclass E members as the most active ERFs in ethylene- and RIN/NOR-dependent ripening. PMID:26739234

Assessing vulnerability to drought: identifying underlying factors across Europe

NASA Astrophysics Data System (ADS)

Urquijo, Julia; Gonzalez Tánago, Itziar; Ballesteros, Mario; De Stefano, Lucia

2015-04-01

Drought is considered one of the most severe and damaging natural hazards in terms of people and sectors affected and associated losses. Drought is a normal and recurrent climatic phenomenon that occurs worldwide, although its spatial and temporal characteristics vary significantly among climates. In the case of Europe, in the last thirty years, the region has suffered several drought events that have caused estimated economic damages over a €100 billion and have affected almost 20% of its territory and population. In recent years, there has been a growing awareness among experts and authorities of the need to shift from a reactive crisis approach to a drought risk management approach, as well as of the importance of designing and implementing policies, strategies and plans at country and river basin levels to deal with drought. The identification of whom and what is vulnerable to drought is a central aspect of drought risk mitigation and planning and several authors agree that societal vulnerability often determines drought risk more than the actual precipitation shortfalls. The final aim of a drought vulnerability assessment is to identify the underlying sources of drought impact, in order to develop policy options that help to enhance coping capacity and therefore to prevent drought impact. This study identifies and maps factors underlying vulnerability to drought across Europe. The identification of factors influencing vulnerability starts from the analysis of past drought impacts in four European socioeconomic sectors. This analysis, along with an extensive literature review, led to the selection of vulnerability factors that are both relevant and adequate for the European context. Adopting the IPCC model, vulnerability factors were grouped to describe exposure, sensitivity and adaptive capacity. The aggregation of these components has resulted in the mapping of vulnerability to drought across Europe at NUTS02 level. Final results have been compared with

Can we identify response markers to antihypertensive drugs? First results from the IDEAL Trial.

PubMed

Gueyffier, F; Subtil, F; Bejan-Angoulvant, T; Zerbib, Y; Baguet, J P; Boivin, J M; Mercier, A; Leftheriotis, G; Gagnol, J P; Fauvel, J P; Giraud, C; Bricca, G; Maucort-Boulch, D; Erpeldinger, S

2015-01-01

Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25-70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was -11.5 mm Hg (indapamide) and -8.3 mm Hg (perindopril). In men, the response was significantly smaller: -4.8 mm Hg (indapamide) and -4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori.

Influence of environmental factors on biotic responses to nutrient enrichment in agricultural streams

USGS Publications Warehouse

Maret, Terry R.; Konrad, Christopher P.; Tranmer, Andrew W.

2010-01-01

The influence of environmental factors on biotic responses to nutrients was examined in three diverse agricultural regions of the United States. Seventy wadeable sites were selected along an agricultural land use gradient while minimizing natural variation within each region. Nutrients, habitat, algae, macroinvertebrates, and macrophyte cover were sampled during a single summer low-flow period in 2006 or 2007. Continuous stream stage and water temperature were collected at each site for 30 days prior to sampling. Wide ranges of concentrations were found for total nitrogen (TN) (0.07-9.61 mg/l) and total phosphorus (TP) (R2) for nutrients and biotic measures across all sites ranged from 0.08 to 0.32 and generally were not higher within each region. The biotic measures (RCHL, SCHL, and AQM) were combined in an index to evaluate eutrophic status across sites that could have different biotic responses to nutrient enrichment. Stepwise multiple regression identified TN, percent canopy, median riffle depth, and daily percent change in stage as significant factors for the eutrophic index (R2 = 0.50, p < 0.001). A TN threshold of 0.48 mg/l was identified where eutrophic index scores became less responsive to increasing TN concentrations, for all sites. Multiple plant growth indicators should be used when evaluating eutrophication, especially when streams contain an abundance of macrophytes.

Bayes Factor Covariance Testing in Item Response Models.

PubMed

Fox, Jean-Paul; Mulder, Joris; Sinharay, Sandip

2017-12-01

Two marginal one-parameter item response theory models are introduced, by integrating out the latent variable or random item parameter. It is shown that both marginal response models are multivariate (probit) models with a compound symmetry covariance structure. Several common hypotheses concerning the underlying covariance structure are evaluated using (fractional) Bayes factor tests. The support for a unidimensional factor (i.e., assumption of local independence) and differential item functioning are evaluated by testing the covariance components. The posterior distribution of common covariance components is obtained in closed form by transforming latent responses with an orthogonal (Helmert) matrix. This posterior distribution is defined as a shifted-inverse-gamma, thereby introducing a default prior and a balanced prior distribution. Based on that, an MCMC algorithm is described to estimate all model parameters and to compute (fractional) Bayes factor tests. Simulation studies are used to show that the (fractional) Bayes factor tests have good properties for testing the underlying covariance structure of binary response data. The method is illustrated with two real data studies.

Pilot Evaluation of Angiogenesis Signaling Factor Response after Transcatheter Arterial Embolization for Hepatocellular Carcinoma.

PubMed

Ronald, James; Nixon, Andrew B; Marin, Daniele; Gupta, Rajan T; Janas, Gemini; Chen, Willa; Suhocki, Paul V; Pabon-Ramos, Waleska; Sopko, David R; Starr, Mark D; Brady, John C; Hurwitz, Herbert I; Kim, Charles Y

2017-10-01

Purpose To identify changes in a broad panel of circulating angiogenesis factors after bland transcatheter arterial embolization (TAE), a purely ischemic treatment for hepatocellular carcinoma (HCC). Materials and Methods This prospective HIPAA-compliant study was approved by the institutional review board. Informed written consent was obtained from all participants prior to entry into the study. Twenty-five patients (21 men; mean age, 61 years; range, 30-81 years) with Liver Imaging Reporting and Data System category 5 or biopsy-proven HCC and who were undergoing TAE were enrolled from October 15, 2014, through December 2, 2015. Nineteen plasma angiogenesis factors (angiopoietin 2; hepatocyte growth factor; platelet-derived growth factor AA and BB; placental growth factor; vascular endothelial growth factor A and D; vascular endothelial growth factor receptor 1, 2, and 3; osteopontin; transforming growth factor β1 and β2; thrombospondin 2; intercellular adhesion molecule 1; interleukin 6 [IL-6]; stromal cell-derived factor 1; tissue inhibitor of metalloproteinases 1; and vascular cell adhesion molecule 1 [VCAM-1]) were measured by using enzyme-linked immunosorbent assays at 1 day, 2 weeks, and 5 weeks after TAE and were compared with baseline levels by using paired Wilcoxon tests. Tumor response was assessed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Angiogenesis factor levels were compared between responders and nonresponders by mRECIST criteria by using unpaired Wilcoxon tests. Results All procedures were technically successful with no complications. Fourteen angiogenesis factors showed statistically significant changes following TAE, but most changes were transient. IL-6 was upregulated only 1 day after the procedure, but showed the largest increases of any factor. Osteopontin and VCAM-1 demonstrated sustained upregulation at all time points following TAE. At 3-month follow-up imaging, 11 patients had responses to TAE

ABFs, a family of ABA-responsive element binding factors.

PubMed

Choi, H; Hong, J; Ha, J; Kang, J; Kim, S Y

2000-01-21

Abscisic acid (ABA) plays an important role in environmental stress responses of higher plants during vegetative growth. One of the ABA-mediated responses is the induced expression of a large number of genes, which is mediated by cis-regulatory elements known as abscisic acid-responsive elements (ABREs). Although a number of ABRE binding transcription factors have been known, they are not specifically from vegetative tissues under induced conditions. Considering the tissue specificity of ABA signaling pathways, factors mediating ABA-dependent stress responses during vegetative growth phase may thus have been unidentified so far. Here, we report a family of ABRE binding factors isolated from young Arabidopsis plants under stress conditions. The factors, isolated by a yeast one-hybrid system using a prototypical ABRE and named as ABFs (ABRE binding factors) belong to a distinct subfamily of bZIP proteins. Binding site selection assay performed with one ABF showed that its preferred binding site is the strong ABRE, CACGTGGC. ABFs can transactivate an ABRE-containing reporter gene in yeast. Expression of ABFs is induced by ABA and various stress treatments, whereas their induction patterns are different from one another. Thus, a new family of ABRE binding factors indeed exists that have the potential to activate a large number of ABA/stress-responsive genes in Arabidopsis.

Identifying antecedent conditions responsible for the high rate of mining injuries in Zambia.

PubMed

Miller, Hugh B; Sinkala, Thomson; Renger, Ralph F; Peacock, Erin M; Tabor, Joseph A; Burgess, Jefferey L

2006-01-01

The incident rates of mining-related accidents and injuries in developing countries exceed those of developed nations. Interventions by international organizations routinely fail to produce appreciable long-term improvement. One major reason is the inability to identify and analyze the underlying factors responsible for creating unsafe working conditions. Understanding these antecedent conditions is necessary to formulate effective intervention strategies and prioritize the use of limited resources. This study utilized a logic model approach to determine the root causes and broad categories of potential interventions for mining accidents and injuries in Zambia. Results showed that policy interventions have the greatest potential for substantive change. A process of educating officials from government and mining companies about the economic and social merits of health and safety programs and extensive changes in regulatory structure and enforcement are needed.

Identifying factors for optimal development of health-related websites: a delphi study among experts and potential future users.

PubMed

Schneider, Francine; van Osch, Liesbeth; de Vries, Hein

2012-02-14

The Internet has become a popular medium for offering tailored and targeted health promotion programs to the general public. However, suboptimal levels of program use in the target population limit the public health impact of these programs. Optimizing program development is considered as one of the main processes to increase usage rates. To distinguish factors potentially related to optimal development of health-related websites by involving both experts and potential users. By considering and incorporating the opinions of experts and potential users in the development process, involvement in the program is expected to increase, consequently resulting in increased appreciation, lower levels of attrition, and higher levels of sustained use. We conducted a systematic three-round Delphi study through the Internet. Both national and international experts (from the fields of health promotion, health psychology, e-communication, and technical Web design) and potential users were invited via email to participate. During this study an extensive list of factors potentially related to optimal development of health-related websites was identified, by focusing on factors related to layout, general and risk information provision, questionnaire use, additional services, and ease of use. Furthermore, we assessed the extent to which experts and potential users agreed on the importance of these factors. Differences as well as similarities among experts and potentials users were deduced. In total, 20 of 62 contacted experts participated in the first round (32% response rate); 60 of 200 contacted experts (30% response rate) and 210 potential users (95% response rate) completed the second-round questionnaire, and 32 of 60 contacted experts completed the third round (53% response rate). Results revealed important factors consented upon by experts and potential users (eg, ease of use, clear structure, and detailed health information provision), as well as differences regarding

Redundant and distinct functions of the ABA response loci ABA-INSENSITIVE(ABI)5 and ABRE-BINDING FACTOR (ABF)3.

PubMed

Finkelstein, Ruth; Gampala, Srinivas S L; Lynch, Tim J; Thomas, Terry L; Rock, Christopher D

2005-09-01

Abscisic acid-responsive gene expression is regulated by numerous transcription factors, including a subgroup of basic leucine zipper factors that bind to the conserved cis-acting sequences known as ABA-responsive elements. Although one of these factors, ABA-insensitive 5 (ABI5), was identified genetically, the paucity of genetic data for the other family members has left it unclear whether they perform unique functions or act redundantly to ABI5 or each other. To test for potential redundancy with ABI5, we identified the family members with most similar effects and interactions in transient expression systems (ABF3 and ABF1), then characterized loss-of-function lines for those loci. The abf1 and abf3 monogenic mutant lines had at most minimal effects on germination or seed-specific gene expression, but the enhanced ABA- and stress-resistance of abf3 abi5 double mutants revealed redundant action of these genes in multiple stress responses of seeds and seedlings. Although ABI5, ABF3, and ABF1 have some overlapping effects, they appear to antagonistically regulate each other's expression at specific stages. Consequently, loss of any one factor may be partially compensated by increased expression of other family members.

Aligning faith-based and national HIV/AIDS prevention responses? Factors influencing the HIV/AIDS prevention policy process and response of faith-based NGOs in Tanzania.

PubMed

Morgan, Rosemary; Green, Andrew; Boesten, Jelke

2014-05-01

Faith-based organizations (FBOs) have a long tradition of providing HIV/AIDS prevention and mitigation services in Africa. The overall response of FBOs, however, has been controversial, particularly in regard to HIV/AIDS prevention and FBO's rejection of condom use and promotion, which can conflict with and negatively influence national HIV/AIDS prevention response efforts. This article reports the findings from a study that explored the factors influencing the HIV/AIDS prevention policy process within faith-based non-governmental organizations (NGOs) of different faiths. These factors were examined within three faith-based NGOs in Dar es Salaam, Tanzania-a Catholic, Anglican and Muslim organization. The research used an exploratory, qualitative case-study approach, and employed a health policy analysis framework, examining the context, actor and process factors and how they interact to form content in terms of policy and its implementation within each organization. Three key factors were found to influence faith-based NGOs' HIV/AIDS prevention response in terms of both policy and its implementation: (1) the faith structure in which the organizations are a part, (2) the presence or absence of organizational policy and (3) the professional nature of the organizations and its actors. The interaction between these factors, and how actors negotiate between them, was found to shape the organizations' HIV/AIDS prevention response. This article reports on these factors and analyses the different HIV/AIDS prevention responses found within each organization. By understanding the factors that influence faith-based NGOs' HIV/AIDS prevention policy process, the overall faith-based response to HIV/AIDS, and how it corresponds to national response efforts, is better understood. It is hoped that by doing so the government will be better able to identify how to best work with FBOs to meet national HIV/AIDS prevention targets, improving the overall role of FBOs in the fight against

Glucose impairs tamoxifen responsiveness modulating connective tissue growth factor in breast cancer cells.

PubMed

Ambrosio, Maria Rosaria; D'Esposito, Vittoria; Costa, Valerio; Liguoro, Domenico; Collina, Francesca; Cantile, Monica; Prevete, Nella; Passaro, Carmela; Mosca, Giusy; De Laurentiis, Michelino; Di Bonito, Maurizio; Botti, Gerardo; Franco, Renato; Beguinot, Francesco; Ciccodicola, Alfredo; Formisano, Pietro

2017-12-12

Type 2 diabetes and obesity are negative prognostic factors in patients with breast cancer (BC). We found that sensitivity to tamoxifen was reduced by 2-fold by 25 mM glucose (High Glucose; HG) compared to 5.5 mM glucose (Low Glucose; LG) in MCF7 BC cells. Shifting from HG to LG ameliorated MCF7 cell responsiveness to tamoxifen. RNA-Sequencing of MCF7 BC cells revealed that cell cycle-related genes were mainly affected by glucose. Connective Tissue Growth Factor (CTGF) was identified as a glucose-induced modulator of cell sensitivity to tamoxifen. Co-culturing MCF7 cells with human adipocytes exposed to HG, enhanced CTGF mRNA levels and reduced tamoxifen responsiveness of BC cells. Inhibition of adipocyte-released IL8 reverted these effects. Interestingly, CTGF immuno-detection in bioptic specimens from women with estrogen receptor positive (ER + ) BC correlated with hormone therapy resistance, distant metastases, reduced overall and disease-free survival. Thus, glucose affects tamoxifen responsiveness directly modulating CTGF in BC cells, and indirectly promoting IL8 release by adipocytes.

Identifying socio-environmental factors that facilitate resilience among Canadian palliative family caregivers: a qualitative case study.

PubMed

Giesbrecht, Melissa; Wolse, Faye; Crooks, Valorie A; Stajduhar, Kelli

2015-06-01

In Canada, friends and family members are becoming increasingly responsible for providing palliative care in the home. This is resulting in some caregivers experiencing high levels of stress and burden that may ultimately surpass their ability to cope. Recent palliative care research has demonstrated the potential for caregiver resilience within such contexts. This research, however, is primarily focused on exploring individual-level factors that contribute to resilience, minimizing the inherent complexity of this concept, and how it is simultaneously influenced by one's social context. Therefore, our study aims to identify socio-environmental factors that contribute to palliative family caregiver resilience in the Canadian homecare context. Drawing on ethnographic fieldnotes and semistructured interviews with family caregivers, care recipients, and homecare nurses, this secondary analysis employs an intersectionality lens and qualitative case study approach to identify socio-environmental factors that facilitate family caregivers' capacity for resilience. Following a case study methodology, two cases are purposely selected for analysis. Findings demonstrate that family caregiver resilience is influenced not only by individual-level factors but also by the social environment, which sets the lived context from which caregiving roles are experienced. Thematic findings of the two case studies revealed six socio-environmental factors that play a role in shaping resilience: access to social networks, education/knowledge/awareness, employment status, housing status, geographic location, and life-course stage. Findings contribute to existing research on caregiver resilience by empirically demonstrating the role of socio-environmental factors in caregiving experiences. Furthermore, utilizing an intersectional approach, these findings build on existing notions that resilience is a multidimensional and complex process influenced by numerous related variables that intersect

Identifying Key Drivers of Return Reversal with Dynamical Bayesian Factor Graph

PubMed Central

Zhao, Shuai; Tong, Yunhai; Wang, Zitian; Tan, Shaohua

2016-01-01

In the stock market, return reversal occurs when investors sell overbought stocks and buy oversold stocks, reversing the stocks’ price trends. In this paper, we develop a new method to identify key drivers of return reversal by incorporating a comprehensive set of factors derived from different economic theories into one unified dynamical Bayesian factor graph. We then use the model to depict factor relationships and their dynamics, from which we make some interesting discoveries about the mechanism behind return reversals. Through extensive experiments on the US stock market, we conclude that among the various factors, the liquidity factors consistently emerge as key drivers of return reversal, which is in support of the theory of liquidity effect. Specifically, we find that stocks with high turnover rates or high Amihud illiquidity measures have a greater probability of experiencing return reversals. Apart from the consistent drivers, we find other drivers of return reversal that generally change from year to year, and they serve as important characteristics for evaluating the trends of stock returns. Besides, we also identify some seldom discussed yet enlightening inter-factor relationships, one of which shows that stocks in Finance and Insurance industry are more likely to have high Amihud illiquidity measures in comparison with those in other industries. These conclusions are robust for return reversals under different thresholds. PMID:27893780

Identifying Key Drivers of Return Reversal with Dynamical Bayesian Factor Graph.

PubMed

Zhao, Shuai; Tong, Yunhai; Wang, Zitian; Tan, Shaohua

2016-01-01

In the stock market, return reversal occurs when investors sell overbought stocks and buy oversold stocks, reversing the stocks' price trends. In this paper, we develop a new method to identify key drivers of return reversal by incorporating a comprehensive set of factors derived from different economic theories into one unified dynamical Bayesian factor graph. We then use the model to depict factor relationships and their dynamics, from which we make some interesting discoveries about the mechanism behind return reversals. Through extensive experiments on the US stock market, we conclude that among the various factors, the liquidity factors consistently emerge as key drivers of return reversal, which is in support of the theory of liquidity effect. Specifically, we find that stocks with high turnover rates or high Amihud illiquidity measures have a greater probability of experiencing return reversals. Apart from the consistent drivers, we find other drivers of return reversal that generally change from year to year, and they serve as important characteristics for evaluating the trends of stock returns. Besides, we also identify some seldom discussed yet enlightening inter-factor relationships, one of which shows that stocks in Finance and Insurance industry are more likely to have high Amihud illiquidity measures in comparison with those in other industries. These conclusions are robust for return reversals under different thresholds.

Transcriptome-wide analysis of WRKY transcription factors in wheat and their leaf rust responsive expression profiling.

PubMed

Satapathy, Lopamudra; Singh, Dharmendra; Ranjan, Prashant; Kumar, Dhananjay; Kumar, Manish; Prabhu, Kumble Vinod; Mukhopadhyay, Kunal

2014-12-01

WRKY, a plant-specific transcription factor family, has important roles in pathogen defense, abiotic cues and phytohormone signaling, yet little is known about their roles and molecular mechanism of function in response to rust diseases in wheat. We identified 100 TaWRKY sequences using wheat Expressed Sequence Tag database of which 22 WRKY sequences were novel. Identified proteins were characterized based on their zinc finger motifs and phylogenetic analysis clustered them into six clades consisting of class IIc and class III WRKY proteins. Functional annotation revealed major functions in metabolic and cellular processes in control plants; whereas response to stimuli, signaling and defense in pathogen inoculated plants, their major molecular function being binding to DNA. Tag-based expression analysis of the identified genes revealed differential expression between mock and Puccinia triticina inoculated wheat near isogenic lines. Gene expression was also performed with six rust-related microarray experiments at Gene Expression Omnibus database. TaWRKY10, 15, 17 and 56 were common in both tag-based and microarray-based differential expression analysis and could be representing rust specific WRKY genes. The obtained results will bestow insight into the functional characterization of WRKY transcription factors responsive to leaf rust pathogenesis that can be used as candidate genes in molecular breeding programs to improve biotic stress tolerance in wheat.

Predictive Factors for Beneficial Response to Interferon-alfa Therapy in Chronic Hepatitis C

PubMed Central

Yoon, Seung-Kew; Kim, Sung Soo; Park, Young Min; Shim, Kyu Sik; Lee, Chang Don; Sun, Hee Sik; Park, Doo Ho; Kim, Boo Sung; Ryu, Wang Shick; Cho, Joong Myung

1995-01-01

Objectives: Interferon is the only established teatment for chronic hepatitis C but the host-dependent or virus-related factors affecting the response rate to interferon therapy are not yet dear. The purpose of this study was to investigate the factors predictive of response to interferon-alfa therapy in chronic hepatitis C. Methods: Twenty-five consecutive patients with chronic hepatitis C were randomized to three regimens of interferon-alfa: group A (n=7, 3MU every day for 3 months), group B (n=8, 3MU every other day for 3 months) and group C (n=10, 3MU every other day for 6 months), We quantified serum HC RNA levels by competitive reverse transcription-polymerase chain reaction (RT-PCR)and performed HCV genotyping using type-specific primers deduced from the NS5 region of the HCV genome. We also attempted to identify which demographic, biochemical and histologic factors in addition to virus-related factors would significantly predict beneficial response to interferon by multivariate analysis. Results: Sustained responders were 8 (36.4%), nonsustained responders were 2 (9.1%) and nonresponders were 12 (54.5%) of 22 patients who had received complete therapy. The initial HCV RNA level (logarithmic transformed copy numbers per ml of serum)in sustained responders (5.75±0.39) was significantly lower than that of nonsustained responders (6.80±0.71)and nonresponders (6.70±0.52) (p<0.05). In multivariate multiple logistic regression analysis, the serum HCV RNA level before therapy was only the independent predictor of a sustained response to interferon-alfa therapy (p=0.001). Conclusions: Serum HCV RNA level before therapy was the most useful predictor of a sustained response to interferon-alfa therapy for chronic hepatitis C. PMID:7495780

Identifying genetic loci affecting antidepressant drug response in depression using drug–gene interaction models

PubMed Central

Noordam, Raymond; Avery, Christy L; Visser, Loes E; Stricker, Bruno H

2016-01-01

Antidepressants are often only moderately successful in decreasing the severity of depressive symptoms. In part, antidepressant treatment response in patients with depression is genetically determined. However, although a large number of studies have been conducted aiming to identify genetic variants associated with antidepressant drug response in depression, only a few variants have been repeatedly identified. Within the present review, we will discuss the methodological challenges and limitations of the studies that have been conducted on this topic to date (e.g., ‘treated-only design’, statistical power) and we will discuss how specifically drug–gene interaction models can be used to be better able to identify genetic variants associated with antidepressant drug response in depression. PMID:27248517

Identification of estrogen-responsive genes using a genome-wide analysis of promoter elements for transcription factor binding sites.

PubMed

Kamalakaran, Sitharthan; Radhakrishnan, Senthil K; Beck, William T

2005-06-03

We developed a pipeline to identify novel genes regulated by the steroid hormone-dependent transcription factor, estrogen receptor, through a systematic analysis of upstream regions of all human and mouse genes. We built a data base of putative promoter regions for 23,077 human and 19,984 mouse transcripts from National Center for Biotechnology Information annotation and 8793 human and 6785 mouse promoters from the Data Base of Transcriptional Start Sites. We used this data base of putative promoters to identify potential targets of estrogen receptor by identifying estrogen response elements (EREs) in their promoters. Our program correctly identified EREs in genes known to be regulated by estrogen in addition to several new genes whose putative promoters contained EREs. We validated six genes (KIAA1243, NRIP1, MADH9, NME3, TPD52L, and ABCG2) to be estrogen-responsive in MCF7 cells using reverse transcription PCR. To allow for extensibility of our program in identifying targets of other transcription factors, we have built a Web interface to access our data base and programs. Our Web-based program for Promoter Analysis of Genome, PAGen@UIC, allows a user to identify putative target genes for vertebrate transcription factors through the analysis of their upstream sequences. The interface allows the user to search the human and mouse promoter data bases for potential target genes containing one or more listed transcription factor binding sites (TFBSs) in their upstream elements, using either regular expression-based consensus or position weight matrices. The data base can also be searched for promoters harboring user-defined TFBSs given as a consensus or a position weight matrix. Furthermore, the user can retrieve putative promoter sequences for any given gene together with identified TFBSs located on its promoter. Orthologous promoters are also analyzed to determine conserved elements.

A reverse genetics approach identifies novel mutants in light responses and anthocyanin metabolism in petunia.

PubMed

Berenschot, Amanda S; Quecini, Vera

2014-01-01

Flower color and plant architecture are important commercially valuable features for ornamental petunias (Petunia x hybrida Vilm.). Photoperception and light signaling are the major environmental factors controlling anthocyanin and chlorophyll biosynthesis and shade-avoidance responses in higher plants. The genetic regulators of these processes were investigated in petunia by in silico analyses and the sequence information was used to devise a reverse genetics approach to probe mutant populations. Petunia orthologs of photoreceptor, light-signaling components and anthocyanin metabolism genes were identified and investigated for functional conservation by phylogenetic and protein motif analyses. The expression profiles of photoreceptor gene families and of transcription factors regulating anthocyanin biosynthesis were obtained by bioinformatic tools. Two mutant populations, generated by an alkalyting agent and by gamma irradiation, were screened using a phenotype-independent, sequence-based method by high-throughput PCR-based assay. The strategy allowed the identification of novel mutant alleles for anthocyanin biosynthesis (CHALCONE SYNTHASE) and regulation (PH4), and for light signaling (CONSTANS) genes.

Bleaching response of coral species in the context of assemblage response

NASA Astrophysics Data System (ADS)

Swain, Timothy D.; DuBois, Emily; Goldberg, Scott J.; Backman, Vadim; Marcelino, Luisa A.

2017-06-01

Caribbean coral reefs are declining due to a mosaic of local and global stresses, including climate change-induced thermal stress. Species and assemblage responses differ due to factors that are not easily identifiable or quantifiable. We calculated a novel species-specific metric of coral bleaching response, taxon- α and - β, which relates the response of a species to that of its assemblages for 16 species over 18 assemblages. By contextualizing species responses within the response of their assemblages, the effects of environmental factors are removed and intrinsic differences among taxa are revealed. Most corals experience either a saturation response, overly sensitive to weak stress ( α > 0) but under-responsive compared to assemblage bleaching ( β < 1), or a threshold response, insensitive to weak stress ( α < 0) but over-responsive compared to assemblage bleaching ( β > 1). This metric may help reveal key factors of bleaching susceptibility and identify species as targets for conservation.

Bleaching response of coral species in the context of assemblage response.

PubMed

Swain, Timothy D; DuBois, Emily; Goldberg, Scott J; Backman, Vadim; Marcelino, Luisa A

2017-06-01

Caribbean coral reefs are declining due to a mosaic of local and global stresses, including climate change-induced thermal stress. Species and assemblage responses differ due to factors that are not easily identifiable or quantifiable. We calculated a novel species-specific metric of coral bleaching response, taxon-α and -β, which relates the response of a species to that of its assemblages for 16 species over 18 assemblages. By contextualizing species responses within the response of their assemblages, the effects of environmental factors are removed and intrinsic differences among taxa are revealed. Most corals experience either a saturation response, overly-sensitive to weak stress (α > 0) but under-responsive compared to assemblage bleaching (β < 1), or a threshold response, insensitive to weak stress (α < 0) but over-responsive compared to assemblage bleaching (β > 1). This metric may help reveal key factors of bleaching susceptibility and identify species as targets for conservation.

Agreement among Response to Intervention Criteria for Identifying Responder Status

ERIC Educational Resources Information Center

Barth, Amy E.; Stuebing, Karla K.; Anthony, Jason L.; Denton, Carolyn A.; Mathes, Patricia G.; Fletcher, Jack M.; Francis, David J.

2008-01-01

In order to better understand the extent to which operationalizations of response to intervention (RTI) overlap and agree in identifying adequate and inadequate responders, an existing database of 399 first grade students was evaluated in relation to cut-points, measures, and methods frequently cited for the identification of inadequate responders…

Impact of identifying factors which trigger bothersome tinnitus on the treatment outcome in tinnitus retraining therapy.

PubMed

Molini, Egisto; Faralli, Mario; Calzolaro, Lucia; Ricci, Giampietro

2014-01-01

The aim of this work was to ascertain any differences in the effectiveness of rehabilitation therapy in relation to the presence or absence of a known negative reinforcement responsible for the tinnitus-related pathology. Between 1 January 2001 and 31 December 2008, we recruited 294 subjects suffering from incapacitating tinnitus and/or hyperacusis. The patients underwent tinnitus retraining therapy (TRT) according to the methods described by Jastreboff and Hazell [Tinnitus Retraining Therapy: Implementing the Neurophysiological Model. Cambridge, Cambridge University Press, 2004, pp 121-133]. We clinically assessed the presence or absence of known phenomena of associative learning, regarding the presence of adverse events temporally correlated with tinnitus and the treatment outcome. The separate analysis of the 2 subgroups shows a statistically significant difference in the improvement rate between the group with a known triggering factor and the group without a triggering factor, with a preponderance of the former with a 91% improvement rate versus approximately 56% for the latter. In our study, the inability to identify factors triggering bothersome tinnitus negatively affected the treatment outcome in TRT. © 2014 S. Karger AG, Basel.

Proteomic analysis of Populus × euramericana (clone I-214) roots to identify key factors involved in zinc stress response.

PubMed

Romeo, Stefania; Trupiano, Dalila; Ariani, Andrea; Renzone, Giovanni; Scippa, Gabriella S; Scaloni, Andrea; Sebastiani, Luca

2014-07-15

Contamination of soil and water by heavy metals has become a widespread problem; environmental pollution by high zinc (Zn) concentration occurs frequently. Although poplar (Populus spp.) has been identified as suitable for phytoremediation approaches, its response to high Zn concentrations are still not clearly understood. For this reason, we investigated the effects of Zn in Populus×euramericana clone I-214 roots by proteomic analysis. Comparative experiments were conducted on rooted woody cuttings grown in nutrient solutions containing 1mM (treatment) or 1μM (control) Zn concentrations. A gel-based proteomic approach coupled with morphological and chemical analysis was used to identify differentially represented proteins in treated roots and to investigate the effect of Zn treatment on the poplar root system. Data shows that Zn was accumulated preferentially in roots, that the antioxidant system, the carbohydrate/energy and amino acid metabolisms were the main pathways modulated by Zn excess, and that mitochondria and vacuoles were the cellular organelles predominately affected by Zn stress. A coordination between cell death and proliferation/growth seems to occur under this condition to counteract the Zn-induced damage. Copyright © 2014 Elsevier GmbH. All rights reserved.

A Global Genomic and Genetic Strategy to Identify, Validate and Use Gene Signatures of Xenobiotic-Responsive Transcription Factors in Prediction of Pathway Activation in the Mouse Liver

EPA Science Inventory

Many drugs and environmentally-relevant chemicals activate xenobiotic-responsive transcription factors. Identification of target genes of these factors would be useful in predicting pathway activation in in vitro chemical screening as well as their involvement in disease states. ...

Identifying transcription factor functions and targets by phenotypic activation

PubMed Central

Chua, Gordon; Morris, Quaid D.; Sopko, Richelle; Robinson, Mark D.; Ryan, Owen; Chan, Esther T.; Frey, Brendan J.; Andrews, Brenda J.; Boone, Charles; Hughes, Timothy R.

2006-01-01

Mapping transcriptional regulatory networks is difficult because many transcription factors (TFs) are activated only under specific conditions. We describe a generic strategy for identifying genes and pathways induced by individual TFs that does not require knowledge of their normal activation cues. Microarray analysis of 55 yeast TFs that caused a growth phenotype when overexpressed showed that the majority caused increased transcript levels of genes in specific physiological categories, suggesting a mechanism for growth inhibition. Induced genes typically included established targets and genes with consensus promoter motifs, if known, indicating that these data are useful for identifying potential new target genes and binding sites. We identified the sequence 5′-TCACGCAA as a binding sequence for Hms1p, a TF that positively regulates pseudohyphal growth and previously had no known motif. The general strategy outlined here presents a straightforward approach to discovery of TF activities and mapping targets that could be adapted to any organism with transgenic technology. PMID:16880382

The Promise of Virtual Teams: Identifying Key Factors in Effectiveness and Failure

ERIC Educational Resources Information Center

Horwitz, Frank M.; Bravington, Desmond; Silvis, Ulrik

2006-01-01

Purpose: The aim of the investigation is to identify enabling and disenabling factors in the development and operation of virtual teams; to evaluate the importance of factors such as team development, cross-cultural variables, leadership, communication and social cohesion as contributors to virtual team effectiveness. Design/methodology/approach:…

Identifying the necessary and sufficient number of risk factors for predicting academic failure.

PubMed

Lucio, Robert; Hunt, Elizabeth; Bornovalova, Marina

2012-03-01

Identifying the point at which individuals become at risk for academic failure (grade point average [GPA] < 2.0) involves an understanding of which and how many factors contribute to poor outcomes. School-related factors appear to be among the many factors that significantly impact academic success or failure. This study focused on 12 school-related factors. Using a thorough 5-step process, we identified which unique risk factors place one at risk for academic failure. Academic engagement, academic expectations, academic self-efficacy, homework completion, school relevance, school safety, teacher relationships (positive relationship), grade retention, school mobility, and school misbehaviors (negative relationship) were uniquely related to GPA even after controlling for all relevant covariates. Next, a receiver operating characteristic curve was used to determine a cutoff point for determining how many risk factors predict academic failure (GPA < 2.0). Results yielded a cutoff point of 2 risk factors for predicting academic failure, which provides a way for early identification of individuals who are at risk. Further implications of these findings are discussed. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Identifying Key Hospital Service Quality Factors in Online Health Communities

PubMed Central

Jung, Yuchul; Hur, Cinyoung; Jung, Dain

2015-01-01

Background The volume of health-related user-created content, especially hospital-related questions and answers in online health communities, has rapidly increased. Patients and caregivers participate in online community activities to share their experiences, exchange information, and ask about recommended or discredited hospitals. However, there is little research on how to identify hospital service quality automatically from the online communities. In the past, in-depth analysis of hospitals has used random sampling surveys. However, such surveys are becoming impractical owing to the rapidly increasing volume of online data and the diverse analysis requirements of related stakeholders. Objective As a solution for utilizing large-scale health-related information, we propose a novel approach to identify hospital service quality factors and overtime trends automatically from online health communities, especially hospital-related questions and answers. Methods We defined social media–based key quality factors for hospitals. In addition, we developed text mining techniques to detect such factors that frequently occur in online health communities. After detecting these factors that represent qualitative aspects of hospitals, we applied a sentiment analysis to recognize the types of recommendations in messages posted within online health communities. Korea’s two biggest online portals were used to test the effectiveness of detection of social media–based key quality factors for hospitals. Results To evaluate the proposed text mining techniques, we performed manual evaluations on the extraction and classification results, such as hospital name, service quality factors, and recommendation types using a random sample of messages (ie, 5.44% (9450/173,748) of the total messages). Service quality factor detection and hospital name extraction achieved average F1 scores of 91% and 78%, respectively. In terms of recommendation classification, performance (ie, precision) is

Identifying key hospital service quality factors in online health communities.

PubMed

Jung, Yuchul; Hur, Cinyoung; Jung, Dain; Kim, Minki

2015-04-07

The volume of health-related user-created content, especially hospital-related questions and answers in online health communities, has rapidly increased. Patients and caregivers participate in online community activities to share their experiences, exchange information, and ask about recommended or discredited hospitals. However, there is little research on how to identify hospital service quality automatically from the online communities. In the past, in-depth analysis of hospitals has used random sampling surveys. However, such surveys are becoming impractical owing to the rapidly increasing volume of online data and the diverse analysis requirements of related stakeholders. As a solution for utilizing large-scale health-related information, we propose a novel approach to identify hospital service quality factors and overtime trends automatically from online health communities, especially hospital-related questions and answers. We defined social media-based key quality factors for hospitals. In addition, we developed text mining techniques to detect such factors that frequently occur in online health communities. After detecting these factors that represent qualitative aspects of hospitals, we applied a sentiment analysis to recognize the types of recommendations in messages posted within online health communities. Korea's two biggest online portals were used to test the effectiveness of detection of social media-based key quality factors for hospitals. To evaluate the proposed text mining techniques, we performed manual evaluations on the extraction and classification results, such as hospital name, service quality factors, and recommendation types using a random sample of messages (ie, 5.44% (9450/173,748) of the total messages). Service quality factor detection and hospital name extraction achieved average F1 scores of 91% and 78%, respectively. In terms of recommendation classification, performance (ie, precision) is 78% on average. Extraction and

Mining whole genomes and transcriptomes of Jatropha (Jatropha curcas) and Castor bean (Ricinus communis) for NBS-LRR genes and defense response associated transcription factors.

PubMed

Sood, Archit; Jaiswal, Varun; Chanumolu, Sree Krishna; Malhotra, Nikhil; Pal, Tarun; Chauhan, Rajinder Singh

2014-11-01

Jatropha (Jatropha curcas L.) and Castor bean (Ricinus communis) are oilseed crops of family Euphorbiaceae with the potential of producing high quality biodiesel and having industrial value. Both the bioenergy plants are becoming susceptible to various biotic stresses directly affecting the oil quality and content. No report exists as of today on analysis of Nucleotide Binding Site-Leucine Rich Repeat (NBS-LRR) gene repertoire and defense response transcription factors in both the plant species. In silico analysis of whole genomes and transcriptomes identified 47 new NBS-LRR genes in both the species and 122 and 318 defense response related transcription factors in Jatropha and Castor bean, respectively. The identified NBS-LRR genes and defense response transcription factors were mapped onto the respective genomes. Common and unique NBS-LRR genes and defense related transcription factors were identified in both the plant species. All NBS-LRR genes in both the species were characterized into Toll/interleukin-1 receptor NBS-LRRs (TNLs) and coiled-coil NBS-LRRs (CNLs), position on contigs, gene clusters and motifs and domains distribution. Transcript abundance or expression values were measured for all NBS-LRR genes and defense response transcription factors, suggesting their functional role. The current study provides a repertoire of NBS-LRR genes and transcription factors which can be used in not only dissecting the molecular basis of disease resistance phenotype but also in developing disease resistant genotypes in Jatropha and Castor bean through transgenic or molecular breeding approaches.

Identification and Expression Profiling of the Auxin Response Factors in Dendrobium officinale under Abiotic Stresses

PubMed Central

Chen, Zhehao; Yuan, Ye; Fu, Di; Shen, Chenjia; Yang, Yanjun

2017-01-01

Auxin response factor (ARF) proteins play roles in plant responses to diverse environmental stresses by binding specifically to the auxin response element in the promoters of target genes. Using our latest public Dendrobium transcriptomes, a comprehensive characterization and analysis of 14 DnARF genes were performed. Three selected DnARFs, including DnARF1, DnARF4, and DnARF6, were confirmed to be nuclear proteins according to their transient expression in epidermal cells of Nicotiana benthamiana leaves. Furthermore, the transcription activation abilities of DnARF1, DnARF4, and DnARF6 were tested in a yeast system. Our data showed that DnARF6 is a transcriptional activator in Dendrobium officinale. To uncover the basic information of DnARF gene responses to abiotic stresses, we analyzed their expression patterns under various hormones and abiotic treatments. Based on our data, several hormones and significant stress responsive DnARF genes have been identified. Since auxin and ARF genes have been identified in many plant species, our data is imperative to reveal the function of ARF mediated auxin signaling in the adaptation to the challenging Dendrobium environment. PMID:28471373

Identification and Expression Profiling of the Auxin Response Factors in Dendrobium officinale under Abiotic Stresses.

PubMed

Chen, Zhehao; Yuan, Ye; Fu, Di; Shen, Chenjia; Yang, Yanjun

2017-05-04

Auxin response factor (ARF) proteins play roles in plant responses to diverse environmental stresses by binding specifically to the auxin response element in the promoters of target genes. Using our latest public Dendrobium transcriptomes, a comprehensive characterization and analysis of 14 DnARF genes were performed. Three selected DnARFs , including DnARF1 , DnARF4 , and DnARF6 , were confirmed to be nuclear proteins according to their transient expression in epidermal cells of Nicotiana benthamiana leaves. Furthermore, the transcription activation abilities of DnARF1 , DnARF4 , and DnARF6 were tested in a yeast system. Our data showed that DnARF6 is a transcriptional activator in Dendrobium officinale . To uncover the basic information of DnARF gene responses to abiotic stresses, we analyzed their expression patterns under various hormones and abiotic treatments. Based on our data, several hormones and significant stress responsive DnARF genes have been identified. Since auxin and ARF genes have been identified in many plant species, our data is imperative to reveal the function of ARF mediated auxin signaling in the adaptation to the challenging Dendrobium environment.

Influence maximization in time bounded network identifies transcription factors regulating perturbed pathways

PubMed Central

Jo, Kyuri; Jung, Inuk; Moon, Ji Hwan; Kim, Sun

2016-01-01

Motivation: To understand the dynamic nature of the biological process, it is crucial to identify perturbed pathways in an altered environment and also to infer regulators that trigger the response. Current time-series analysis methods, however, are not powerful enough to identify perturbed pathways and regulators simultaneously. Widely used methods include methods to determine gene sets such as differentially expressed genes or gene clusters and these genes sets need to be further interpreted in terms of biological pathways using other tools. Most pathway analysis methods are not designed for time series data and they do not consider gene-gene influence on the time dimension. Results: In this article, we propose a novel time-series analysis method TimeTP for determining transcription factors (TFs) regulating pathway perturbation, which narrows the focus to perturbed sub-pathways and utilizes the gene regulatory network and protein–protein interaction network to locate TFs triggering the perturbation. TimeTP first identifies perturbed sub-pathways that propagate the expression changes along the time. Starting points of the perturbed sub-pathways are mapped into the network and the most influential TFs are determined by influence maximization technique. The analysis result is visually summarized in TF-Pathway map in time clock. TimeTP was applied to PIK3CA knock-in dataset and found significant sub-pathways and their regulators relevant to the PIP3 signaling pathway. Availability and Implementation: TimeTP is implemented in Python and available at http://biohealth.snu.ac.kr/software/TimeTP/. Supplementary information: Supplementary data are available at Bioinformatics online. Contact: sunkim.bioinfo@snu.ac.kr PMID:27307609

Identifying Human Factors Issues in Aircraft Maintenance Operations

NASA Technical Reports Server (NTRS)

Veinott, Elizabeth S.; Kanki, Barbara G.; Shafto, Michael G. (Technical Monitor)

1995-01-01

Maintenance operations incidents submitted to the Aviation Safety Reporting System (ASRS) between 1986-1992 were systematically analyzed in order to identify issues relevant to human factors and crew coordination. This exploratory analysis involved 95 ASRS reports which represented a wide range of maintenance incidents. The reports were coded and analyzed according to the type of error (e.g, wrong part, procedural error, non-procedural error), contributing factors (e.g., individual, within-team, cross-team, procedure, tools), result of the error (e.g., aircraft damage or not) as well as the operational impact (e.g., aircraft flown to destination, air return, delay at gate). The main findings indicate that procedural errors were most common (48.4%) and that individual and team actions contributed to the errors in more than 50% of the cases. As for operational results, most errors were either corrected after landing at the destination (51.6%) or required the flight crew to stop enroute (29.5%). Interactions among these variables are also discussed. This analysis is a first step toward developing a taxonomy of crew coordination problems in maintenance. By understanding what variables are important and how they are interrelated, we may develop intervention strategies that are better tailored to the human factor issues involved.

Transcriptional activation of transforming growth factor alpha by estradiol: requirement for both a GC-rich site and an estrogen response element half-site.

PubMed

Vyhlidal, C; Samudio, I; Kladde, M P; Safe, S

2000-06-01

17beta-Estradiol (E2) induces transforming growth factor alpha (TGFalpha) gene expression in MCF-7 cells and previous studies have identified a 53 bp (-252 to -200) sequence containing two imperfect estrogen responsive elements (EREs) that contribute to E2 responsiveness. Deletion analysis of the TGFalpha gene promoter in this study identified a second upstream region of the promoter (-623 to -549) that is also E2 responsive. This sequence contains three GC-rich sites and an imperfect ERE half-site, and the specific cis-elements and trans-acting factors were determined by promoter analysis in transient transfection experiments, gel mobility shift assays and in vitro DNA footprinting. The results are consistent with an estrogen receptor alpha (ERalpha)/Sp1 complex interacting with an Sp1(N)(30) ERE half-site ((1/2)) motif in which both ERalpha and Sp1 bind promoter DNA. The ER/Sp1-DNA complex is formed using nuclear extracts from MCF-7 cells but not with recombinant human ERalpha or Sp1 proteins, suggesting that other nuclear factor(s) are required for complex stabilization. The E2-responsive Sp1(N)(x)ERE(1/2) motif identified in the TGFalpha gene promoter has also been characterized in the cathepsin D and heat shock protein 27 gene promoters; however, in the latter two promoters the numbers of intervening nucleotides are 23 and 10 respectively.

Identifying work ability promoting factors for home care aides and assistant nurses.

PubMed

Larsson, Agneta; Karlqvist, Lena; Westerberg, Mats; Gard, Gunvor

2012-01-11

In workplace health promotion, all potential resources needs to be taken into consideration, not only factors relating to the absence of injury and the physical health of the workers, but also psychological aspects. A dynamic balance between the resources of the individual employees and the demands of work is an important prerequisite. In the home care services, there is a noticeable trend towards increased psychosocial strain on employees at work. There are a high frequency of work-related musculoskeletal disorders and injuries, and a low prevalence of sustainable work ability. The aim of this research was to identify factors promoting work ability and self-efficacy in care aides and assistant nurses within home care services. This study is based on cross-sectional data collected in a municipality in northern Sweden. Care aides (n = 58) and assistant nurses (n = 79) replied to a self-administered questionnaire (response rate 46%). Hierarchical multiple regression analyses were performed to assess the influence of several independent variables on self-efficacy (model 1) and work ability (model 2) for care aides and assistant nurses separately. Perceptions of personal safety, self-efficacy and musculoskeletal wellbeing contributed to work ability for assistant nurses (R2adj of 0.36, p < 0.001), while for care aides, the safety climate, seniority and age contributed to work ability (R2adj of 0.29, p = 0.001). Self-efficacy was associated with the safety climate and the physical demands of the job in both professions (R2adj of 0.24, p = 0.003 for care aides), and also by sex and age for the assistant nurses (R2adj of 0.31, p < 0.001). The intermediate factors contributed differently to work ability in the two professions. Self-efficacy, personal safety and musculoskeletal wellbeing were important for the assistant nurses, while the work ability of the care aides was associated with the safety climate, but also with the non-changeable factors age and seniority. All

Identifying work ability promoting factors for home care aides and assistant nurses

PubMed Central

2012-01-01

Background In workplace health promotion, all potential resources needs to be taken into consideration, not only factors relating to the absence of injury and the physical health of the workers, but also psychological aspects. A dynamic balance between the resources of the individual employees and the demands of work is an important prerequisite. In the home care services, there is a noticeable trend towards increased psychosocial strain on employees at work. There are a high frequency of work-related musculoskeletal disorders and injuries, and a low prevalence of sustainable work ability. The aim of this research was to identify factors promoting work ability and self-efficacy in care aides and assistant nurses within home care services. Methods This study is based on cross-sectional data collected in a municipality in northern Sweden. Care aides (n = 58) and assistant nurses (n = 79) replied to a self-administered questionnaire (response rate 46%). Hierarchical multiple regression analyses were performed to assess the influence of several independent variables on self-efficacy (model 1) and work ability (model 2) for care aides and assistant nurses separately. Results Perceptions of personal safety, self-efficacy and musculoskeletal wellbeing contributed to work ability for assistant nurses (R2adj of 0.36, p < 0.001), while for care aides, the safety climate, seniority and age contributed to work ability (R2adj of 0.29, p = 0.001). Self-efficacy was associated with the safety climate and the physical demands of the job in both professions (R2adj of 0.24, p = 0.003 for care aides), and also by sex and age for the assistant nurses (R2adj of 0.31, p < 0.001). Conclusions The intermediate factors contributed differently to work ability in the two professions. Self-efficacy, personal safety and musculoskeletal wellbeing were important for the assistant nurses, while the work ability of the care aides was associated with the safety climate, but also with the non

Transcriptional regulation of drought response: a tortuous network of transcriptional factors

PubMed Central

Singh, Dhriti; Laxmi, Ashverya

2015-01-01

Drought is one of the leading factors responsible for the reduction in crop yield worldwide. Due to climate change, in future, more areas are going to be affected by drought and for prolonged periods. Therefore, understanding the mechanisms underlying the drought response is one of the major scientific concerns for improving crop yield. Plants deploy diverse strategies and mechanisms to respond and tolerate drought stress. Expression of numerous genes is modulated in different plants under drought stress that help them to optimize their growth and development. Plant hormone abscisic acid (ABA) plays a major role in plant response and tolerance by regulating the expression of many genes under drought stress. Transcription factors being the major regulator of gene expression play a crucial role in stress response. ABA regulates the expression of most of the target genes through ABA-responsive element (ABRE) binding protein/ABRE binding factor (AREB/ABF) transcription factors. Genes regulated by AREB/ABFs constitute a regulon termed as AREB/ABF regulon. In addition to this, drought responsive genes are also regulated by ABA-independent mechanisms. In ABA-independent regulation, dehydration-responsive element binding protein (DREB), NAM, ATAF, and CUC regulons play an important role by regulating many drought-responsive genes. Apart from these major regulons, MYB/MYC, WRKY, and nuclear factor-Y (NF-Y) transcription factors are also involved in drought response and tolerance. Our understanding about transcriptional regulation of drought is still evolving. Recent reports have suggested the existence of crosstalk between different transcription factors operating under drought stress. In this article, we have reviewed various regulons working under drought stress and their crosstalk with each other. PMID:26579147

Predictive factors of clinical response in steroid-refractory ulcerative colitis treated with granulocyte-monocyte apheresis

PubMed Central

D'Ovidio, Valeria; Meo, Donatella; Viscido, Angelo; Bresci, Giampaolo; Vernia, Piero; Caprilli, Renzo

2011-01-01

AIM: To identify factors predicting the clinical response of ulcerative colitis patients to granulocyte-monocyte apheresis (GMA). METHODS: Sixty-nine ulcerative colitis patients (39 F, 30 M) dependent upon/refractory to steroids were treated with GMA. Steroid dependency, clinical activity index (CAI), C reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), values at baseline, use of immunosuppressant, duration of disease, and age and extent of disease were considered for statistical analysis as predictive factors of clinical response. Univariate and multivariate logistic regression models were used. RESULTS: In the univariate analysis, CAI (P = 0.039) and ESR (P = 0.017) levels at baseline were singled out as predictive of clinical remission. In the multivariate analysis steroid dependency [Odds ratio (OR) = 0.390, 95% Confidence interval (CI): 0.176-0.865, Wald 5.361, P = 0.0160] and low CAI levels at baseline (4 < CAI < 7) (OR = 0.770, 95% CI: 0.425-1.394, Wald 3.747, P = 0.028) proved to be effective as factors predicting clinical response. CONCLUSION: GMA may be a valid therapeutic option for steroid-dependent ulcerative colitis patients with mild-moderate disease and its clinical efficacy seems to persist for 12 mo. PMID:21528055

Key Response Planning Factors for the Aftermath of Nuclear Terrorism

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

Buddemeier, B R; Dillon, M B

Despite hundreds of above-ground nuclear tests and data gathered from Hiroshima and Nagasaki, the effects of a ground-level, low-yield nuclear detonation in a modern urban environment are still the subject of considerable scientific debate. Extensive review of nuclear weapon effects studies and discussions with nuclear weapon effects experts from various federal agencies, national laboratories, and technical organizations have identified key issues and bounded some of the unknowns required to support response planning for a low-yield, ground-level nuclear detonation in a modern U.S. city. This study, which is focused primarily upon the hazards posed by radioactive fallout, used detailed fallout predictionsmore » from the advanced suite of three-dimensional (3-D) meteorology and plume/fallout models developed at Lawrence Livermore National Laboratory (LLNL), including extensive global Key Response Planning Factors for the Aftermath of Nuclear Terrorism geographical and real-time meteorological databases to support model calculations. This 3-D modeling system provides detailed simulations that account for complex meteorology and terrain effects. The results of initial modeling and analysis were presented to federal, state, and local working groups to obtain critical, broad-based review and feedback on strategy and messaging. This effort involved a diverse set of communities, including New York City, National Capitol Regions, Charlotte, Houston, Portland, and Los Angeles. The largest potential for reducing casualties during the post-detonation response phase comes from reducing exposure to fallout radiation. This can be accomplished through early, adequate sheltering followed by informed, delayed evacuation.B The response challenges to a nuclear detonation must be solved through multiple approaches of public education, planning, and rapid response actions. Because the successful response will require extensive coordination of a large number of organizations

What Makes Sports Fans Interactive? Identifying Factors Affecting Chat Interactions in Online Sports Viewing

PubMed Central

Yeo, Jaeryong; Lee, Juyeong

2016-01-01

Sports fans are able to watch games from many locations using TV services while interacting with other fans online. In this paper, we identify the factors that affect sports viewers’ online interactions. Using a large-scale dataset of more than 25 million chat messages from a popular social TV site for baseball, we extract various game-related factors, and investigate the relationships between these factors and fans’ interactions using a series of multiple regression analyses. As a result, we identify several factors that are significantly related to viewer interactions. In addition, we determine that the influence of these factors varies according to the user group; i.e., active vs. less active users, and loyal vs. non-loyal users. PMID:26849568

Experimental Infections with Mycoplasma agalactiae Identify Key Factors Involved in Host-Colonization

PubMed Central

Baranowski, Eric; Bergonier, Dominique; Sagné, Eveline; Hygonenq, Marie-Claude; Ronsin, Patricia; Berthelot, Xavier; Citti, Christine

2014-01-01

Mechanisms underlying pathogenic processes in mycoplasma infections are poorly understood, mainly because of limited sequence similarities with classical, bacterial virulence factors. Recently, large-scale transposon mutagenesis in the ruminant pathogen Mycoplasma agalactiae identified the NIF locus, including nifS and nifU, as essential for mycoplasma growth in cell culture, while dispensable in axenic media. To evaluate the importance of this locus in vivo, the infectivity of two knock-out mutants was tested upon experimental infection in the natural host. In this model, the parental PG2 strain was able to establish a systemic infection in lactating ewes, colonizing various body sites such as lymph nodes and the mammary gland, even when inoculated at low doses. In these PG2-infected ewes, we observed over the course of infection (i) the development of a specific antibody response and (ii) dynamic changes in expression of M. agalactiae surface variable proteins (Vpma), with multiple Vpma profiles co-existing in the same animal. In contrast and despite a sensitive model, none of the knock-out mutants were able to survive and colonize the host. The extreme avirulent phenotype of the two mutants was further supported by the absence of an IgG response in inoculated animals. The exact role of the NIF locus remains to be elucidated but these data demonstrate that it plays a key role in the infectious process of M. agalactiae and most likely of other pathogenic mycoplasma species as many carry closely related homologs. PMID:24699671

Combining Knowledge and Data Driven Insights for Identifying Risk Factors using Electronic Health Records

PubMed Central

Sun, Jimeng; Hu, Jianying; Luo, Dijun; Markatou, Marianthi; Wang, Fei; Edabollahi, Shahram; Steinhubl, Steven E.; Daar, Zahra; Stewart, Walter F.

2012-01-01

Background: The ability to identify the risk factors related to an adverse condition, e.g., heart failures (HF) diagnosis, is very important for improving care quality and reducing cost. Existing approaches for risk factor identification are either knowledge driven (from guidelines or literatures) or data driven (from observational data). No existing method provides a model to effectively combine expert knowledge with data driven insight for risk factor identification. Methods: We present a systematic approach to enhance known knowledge-based risk factors with additional potential risk factors derived from data. The core of our approach is a sparse regression model with regularization terms that correspond to both knowledge and data driven risk factors. Results: The approach is validated using a large dataset containing 4,644 heart failure cases and 45,981 controls. The outpatient electronic health records (EHRs) for these patients include diagnosis, medication, lab results from 2003–2010. We demonstrate that the proposed method can identify complementary risk factors that are not in the existing known factors and can better predict the onset of HF. We quantitatively compare different sets of risk factors in the context of predicting onset of HF using the performance metric, the Area Under the ROC Curve (AUC). The combined risk factors between knowledge and data significantly outperform knowledge-based risk factors alone. Furthermore, those additional risk factors are confirmed to be clinically meaningful by a cardiologist. Conclusion: We present a systematic framework for combining knowledge and data driven insights for risk factor identification. We demonstrate the power of this framework in the context of predicting onset of HF, where our approach can successfully identify intuitive and predictive risk factors beyond a set of known HF risk factors. PMID:23304365

Influence of Environmental Factors on Biotic Responses to Nutrient Enrichment in Agricultural Streams1

PubMed Central

Maret, Terry R; Konrad, Christopher P; Tranmer, Andrew W

2010-01-01

The influence of environmental factors on biotic responses to nutrients was examined in three diverse agricultural regions of the United States. Seventy wadeable sites were selected along an agricultural land use gradient while minimizing natural variation within each region. Nutrients, habitat, algae, macroinvertebrates, and macrophyte cover were sampled during a single summer low-flow period in 2006 or 2007. Continuous stream stage and water temperature were collected at each site for 30 days prior to sampling. Wide ranges of concentrations were found for total nitrogen (TN) (0.07-9.61 mg/l) and total phosphorus (TP) (<0.004-0.361 mg/l), but biotic responses including periphytic and sestonic chlorophyll a (RCHL and SCHL, respectively), and percent of stream bed with aquatic macrophyte (AQM) growth were not strongly related to concentrations of TN or TP. Pearson’s coefficient of determination (R2) for nutrients and biotic measures across all sites ranged from 0.08 to 0.32 and generally were not higher within each region. The biotic measures (RCHL, SCHL, and AQM) were combined in an index to evaluate eutrophic status across sites that could have different biotic responses to nutrient enrichment. Stepwise multiple regression identified TN, percent canopy, median riffle depth, and daily percent change in stage as significant factors for the eutrophic index (R2 = 0.50, p < 0.001). A TN threshold of 0.48 mg/l was identified where eutrophic index scores became less responsive to increasing TN concentrations, for all sites. Multiple plant growth indicators should be used when evaluating eutrophication, especially when streams contain an abundance of macrophytes. PMID:22457568

Sexual harassment: identifying risk factors.

PubMed

O'Hare, E A; O'Donohue, W

1998-12-01

A new model of the etiology of sexual harassment, the four-factor model, is presented and compared with several models of sexual harassment including the biological model, the organizational model, the sociocultural model, and the sex role spillover model. A number of risk factors associated with sexually harassing behavior are examined within the framework of the four-factor model of sexual harassment. These include characteristics of the work environment (e.g., sexist attitudes among co-workers, unprofessional work environment, skewed sex ratios in the workplace, knowledge of grievance procedures for sexual harassment incidents) as well as personal characteristics of the subject (e.g., physical attractiveness, job status, sex-role). Subjects were 266 university female faculty, staff, and students who completed the Sexual Experience Questionnaire to assess the experience of sexual harassment and a questionnaire designed to assess the risk factors stated above. Results indicated that the four-factor model is a better predictor of sexual harassment than the alternative models. The risk factors most strongly associated with sexual harassment were an unprofessional environment in the workplace, sexist atmosphere, and lack of knowledge about the organization's formal grievance procedures.

Prealbumin, platelet factor 4 and S100A12 combination at baseline predicts good response to TNF alpha inhibitors in Rheumatoid Arthritis.

PubMed

Nguyen, Minh Vu Chuong; Baillet, Athan; Romand, Xavier; Trocmé, Candice; Courtier, Anaïs; Marotte, Hubert; Thomas, Thierry; Soubrier, Martin; Miossec, Pierre; Tébib, Jacques; Grange, Laurent; Toussaint, Bertrand; Lequerré, Thierry; Vittecoq, Olivier; Gaudin, Philippe

2018-06-06

Tumour necrosis factor-alpha inhibitors (TNFi) are effective treatments for Rheumatoid Arthritis (RA). Responses to treatment are barely predictable. As these treatments are costly and may induce a number of side effects, we aimed at identifying a panel of protein biomarkers that could be used to predict clinical response to TNFi for RA patients. Baseline blood levels of C-reactive protein, platelet factor 4, apolipoprotein A1, prealbumin, α1-antitrypsin, haptoglobin, S100A8/A9 and S100A12 proteins in bDMARD naive patients at the time of TNFi treatment initiation were assessed in a multicentric prospective French cohort. Patients fulfilling good EULAR response at 6 months were considered as responders. Logistic regression was used to determine best biomarker set that could predict good clinical response to TNFi. A combination of biomarkers (prealbumin, platelet factor 4 and S100A12) was identified and could predict response to TNFi in RA with sensitivity of 78%, specificity of 77%, positive predictive values (PPV) of 72%, negative predictive values (NPV) of 82%, positive likelihood ratio (LR+) of 3.35 and negative likelihood ratio (LR-) of 0.28. Lower levels of prealbumin and S100A12 and higher level of platelet factor 4 than the determined cutoff at baseline in RA patients are good predictors for response to TNFi treatment globally as well as to Infliximab, Etanercept and Adalimumab individually. A multivariate model combining 3 biomarkers (prealbumin, platelet factor 4 and S100A12) accurately predicted response of RA patients to TNFi and has potential in a daily practice personalized treatment. Copyright © 2018. Published by Elsevier Masson SAS.

Correctional Officers and Workplace Adversity: Identifying Interpersonal, Cognitive, and Behavioral Response Tendencies.

PubMed

Trounson, Justin S; Pfeifer, Jeffrey E

2017-10-01

This study explored correctional officers' response tendencies (i.e., cognitive, interpersonal, and behavioral response patterns they engage in) when managing workplace adversity. In total, 53 Australian correctional officers participated in the study. Eight exploratory focus group discussions ( n = 42) were conducted to identify a set of officer-endorsed response tendencies. Thematic analysis of group data revealed that correctional officers engage in a range of response tendencies when facing workplace adversity and that these tendencies may be categorized as interpersonally, cognitively, or behaviorally based. Semistructured interviews ( n = 11) were then conducted to provide further depth of information regarding officer response tendency usage. Results are discussed in terms of common themes, future research, and implications for developing training programs designed to ameliorate the effects of workplace adversity.

RM-DEMATEL: a new methodology to identify the key factors in PM2.5.

PubMed

Chen, Yafeng; Liu, Jie; Li, Yunpeng; Sadiq, Rehan; Deng, Yong

2015-04-01

Weather system is a relative complex dynamic system, the factors of the system are mutually influenced PM2.5 concentration. In this paper, a new method is proposed to quantify the influence on PM2.5 by other factors in the weather system and identify the most important factors for PM2.5 with limited resources. The relation map (RM) is used to figure out the direct relation matrix of 14 factors in PM2.5. The decision making trial and evaluation laboratory(DEMATEL) is applied to calculate the causal relationship and extent to a mutual influence of 14 factors in PM2.5. According to the ranking results of our proposed method, the most important key factors is sulfur dioxide (SO2) and nitrogen oxides (NO(X)). In addition, the other factors, the ambient maximum temperature (T(max)), concentration of PM10, and wind direction (W(dir)), are important factors for PM2.5. The proposed method can also be applied to other environment management systems to identify key factors.

Suppressors of systemin signaling identify genes in the tomato wound response pathway.

PubMed Central

Howe, G A; Ryan, C A

1999-01-01

In tomato plants, systemic induction of defense genes in response to herbivory or mechanical wounding is regulated by an 18-amino-acid peptide signal called systemin. Transgenic plants that overexpress prosystemin, the systemin precursor, from a 35S::prosystemin (35S::prosys) transgene exhibit constitutive expression of wound-inducible defense proteins including proteinase inhibitors and polyphenol oxidase. To study further the role of (pro)systemin in the wound response pathway, we isolated and characterized mutations that suppress 35S::prosys-mediated phenotypes. Ten recessive, extragenic suppressors were identified. Two of these define new alleles of def-1, a previously identified mutation that blocks both wound- and systemin-induced gene expression and renders plants susceptible to herbivory. The remaining mutants defined four loci designated Spr-1, Spr-2, Spr-3, and Spr-4 (for Suppressed in 35S::prosystemin-mediated responses). spr-3 and spr-4 mutants were not significantly affected in their response to either systemin or mechanical wounding. In contrast, spr-1 and spr-2 plants lacked systemic wound responses and were insensitive to systemin. These results confirm the function of (pro)systemin in the transduction of systemic wound signals and further establish that wounding, systemin, and 35S::prosys induce defensive gene expression through a common signaling pathway defined by at least three genes (Def-1, Spr-1, and Spr-2). PMID:10545469

NECAP 4.1: NASA's Energy Cost Analysis Program thermal response factor routine

NASA Astrophysics Data System (ADS)

Weise, M. R.

1982-08-01

A thermal response factor is described and calculation sequences and flowcharts for RESFAC2 are provided. RESFAC is used by NASA's (NECAP) to calculate hourly heat transfer coefficients (thermal response factors) for each unique delayed surface. NECAP uses these response factors to compute each spaces' hourly heat gain/loss.

Hazardous drinking and military community functioning: identifying mediating risk factors.

PubMed

Foran, Heather M; Heyman, Richard E; Slep, Amy M Smith

2011-08-01

Hazardous drinking is a serious societal concern in military populations. Efforts to reduce hazardous drinking among military personnel have been limited in effectiveness. There is a need for a deeper understanding of how community-based prevention models apply to hazardous drinking in the military. Community-wide prevention efforts may be most effective in targeting community functioning (e.g., support from formal agencies, community cohesion) that impacts hazardous drinking via other proximal risk factors. The goal of the current study is to inform community-wide prevention efforts by testing a model of community functioning and mediating risk factors of hazardous drinking among active duty U.S. Air Force personnel. A large, representative survey sample of U.S. Air Force active duty members (N = 52,780) was collected at 82 bases worldwide. Hazardous drinking was assessed with the widely used Alcohol Use Disorders Identification Test (Saunders, Aasland, Babor, de la Fuente, & Grant, 1993). A variety of individual, family, and community measures were also assessed. Structural equation modeling was used to test a hypothesized model of community functioning, mediating risk factors and hazardous drinking. Depressive symptoms, perceived financial stress, and satisfaction with the U.S. Air Force were identified as significant mediators of the link between community functioning and hazardous drinking for men and women. Relationship satisfaction was also identified as a mediator for men. These results provide a framework for further community prevention research and suggest that prevention efforts geared at increasing aspects of community functioning (e.g., the U.S. Air Force Community Capacity model) may indirectly lead to reductions in hazardous drinking through other proximal risk factors.

Using an interdisciplinary approach to identify factors that affect clinicians' compliance with evidence-based guidelines.

PubMed

Gurses, Ayse P; Marsteller, Jill A; Ozok, A Ant; Xiao, Yan; Owens, Sharon; Pronovost, Peter J

2010-08-01

Our objective was to identify factors that affect clinicians' compliance with the evidence-based guidelines using an interdisciplinary approach and develop a conceptual framework that can provide a comprehensive and practical guide for designing effective interventions. A literature review and a brainstorming session with 11 researchers from a variety of scientific disciplines were used to identify theoretical and conceptual models describing clinicians' guideline compliance. MEDLINE, EMBASE, CINAHL, and the bibliographies of the papers identified were used as data sources for identifying the relevant theoretical and conceptual models. Thirteen different models that originated from various disciplines including medicine, rural sociology, psychology, human factors and systems engineering, organizational management, marketing, and health education were identified. Four main categories of factors that affect compliance emerged from our analysis: clinician characteristics, guideline characteristics, system characteristics, and implementation characteristics. Based on these findings, we developed an interdisciplinary conceptual framework that specifies the expected interrelationships among these four categories of factors and their impact on clinicians' compliance. An interdisciplinary approach is needed to improve clinicians' compliance with evidence-based guidelines. The conceptual framework from this research can provide a comprehensive and systematic guide to identify barriers to guideline compliance and design effective interventions to improve patient safety.

Suicidality among College and University Students: Contributing Factors and Preventive Response.

ERIC Educational Resources Information Center

Jones, Joan Wickham

This paper surveys and evaluates the research since 1975 on college and university student suicidality in the United States. It focuses on factors which contribute to suicidality, preventive responses to suicide and how well the preventive responses address the contributing factors. Contributing factors examined include various feeling states…

Weak Satiety Responsiveness Is a Reliable Trait Associated with Hedonic Risk Factors for Overeating among Women.

PubMed

Dalton, Michelle; Hollingworth, Sophie; Blundell, John; Finlayson, Graham

2015-09-04

Some individuals exhibit a weak satiety response to food and may be susceptible to overconsumption. The current study identified women showing consistently low or high satiety responses to standardised servings of food across four separate days and compared them on behavioural, psychological and physiological risk factors for overeating and future weight gain. In a crossover design, 30 female participants (age: 28.0 ± 10.6; body mass index (BMI): 23.1 ± 3.0) recorded sensations of hunger in the post-prandial period following four graded energy level breakfasts. Satiety quotients were calculated to compare individuals on satiety responsiveness across conditions. Body composition, resting metabolic rate (RMR), energy intake, food reward and craving, and eating behaviour traits were assessed under controlled laboratory conditions. A distinct low satiety phenotype (LSP) was identified with good consistency across separate study days. These individuals had a higher RMR, greater levels of disinhibition and reported feeling lower control over food cravings. Further, they consumed more energy and exhibited greater wanting for high-fat food. The inverse pattern of characteristics was observed in those exhibiting a consistently high satiety phenotype (HSP). Weak satiety responsiveness is a reliable trait identifiable using the satiety quotient. The LSP was characterised by distinct behavioural and psychological characteristics indicating a risk for overeating, compared to HSP.

Identifying Dust Sources by Positive Matrix Factorization (PMF)

NASA Astrophysics Data System (ADS)

Engelbrecht, Johann P.

2010-05-01

elemental species was modeled by PMF. A five factor solution identified three soil factors, a silicate soil, limestone soil, and a gypsum soil, as well as a salt factor and an anthropogenic metal factor. Similarly, a set of 362 quartz filter samples analyzed for 10 selected chemical species was modeled by PMF. A five factor solution provided a limestone-gypsum soil, diesel combustion, secondary ammonium sulfate, salt and agricultural-burnpit combustion source type. Examples of time series plots of PMF factor contributions for each of six sampling sites (Balad, Baghdad, Tallil, Tikrit, Taji, and Al Asad) will be discussed. Engelbrecht , J. P., McDonald, E. V., Gillies, J. A., Jayanty, R. K. M., Casuccio, G., and Gertler, A. W., 2009, Characterizing mineral dusts and other aerosols from the Middle East - Part 1: Ambient sampling: Inhalation Toxicology, v. 21, p. 297-326.

Factors influencing the pathways in response to complaints.

PubMed

Hsieh, Sophie Yahui

2010-01-01

The purpose of this paper is to explore hospital staff response to patient complaints and the factors influencing the response pathway. The paper uses an exploratory study in a large Taiwanese hospital purposefully chosen as a case study site. The critical incident technique (CIT) is implemented, using a questionnaire along with non-participant observations in which the results have been triangulated. A total of 59 cases were collected. The study found when facing "humaneness" complaints, hospital staff attempted to investigate the event and then explain the facts to the complainant or empathise with him/her and then refer the problem to the relevant unit. In response to complaints combining "communication" and "care/treatment and humaneness", staff tended to investigate the event's details and then directly explain them to the complainant. When complaints involved "care/treatment", staff tended to empathise with the complainant, investigate the facts and explain them to the complainant. Additionally, the organisational response to complaints was influenced by who made complaints; its type, severity, complaining method and patient status. The literature revealed that the case study is the most common organisational study method. However, this approach is criticised for not offering findings that can be generalised. Complaint nature is the major factor influencing the response pathway. If healthcare managers intend to reduce complaint rates then they need to carefully classify the complaint's nature. Different complaints have different handling procedures and guidelines to help managers resolve complaints in the first place. There are extensive studies focusing on investigating complaints and their resolution. These studies tend not to demonstrate various means of handling patient complaints. Neither do they describe how different complaints might lead to different outcomes. Therefore, this paper explores hospital staff response to patient complaints and the factors

Identifying important motivational factors for professionals in Greek hospitals

PubMed Central

Kontodimopoulos, Nick; Paleologou, Victoria; Niakas, Dimitris

2009-01-01

Background The purpose of this study was to identify important motivational factors according to the views of health-care professionals in Greek hospitals and particularly to determine if these might differ in the public and private sectors. Methods A previously developed -and validated- instrument addressing four work-related motivators (job attributes, remuneration, co-workers and achievements) was used. Three categories of health care professionals, doctors (N = 354), nurses (N = 581) and office workers (N = 418), working in public and private hospitals, participated and motivation was compared across socio-demographic and occupational variables. Results The range of reported motivational factors was mixed and Maslow's conclusions that lower level motivational factors must be met before ascending to the next level were not confirmed. The highest ranked motivator for the entire sample, and by professional subgroup, was achievements (P < 0.001). Within subgroups, motivators were similar, and only one significant difference was observed, namely between doctors and nurses in respect to co-workers (P < 0.05). Remuneration (and salary in particular) was reported as a significant incentive only for professionals in managerial positions. Health professionals in private hospitals were motivated by all factors significantly more than their public-hospital counterparts. Conclusion The results are in agreement with the literature which focuses attention to management approaches employing both monetary and non-monetary incentives to motivate health care workers. This study showed that intrinsic factors are particularly important and should become a target for effective employee motivation. PMID:19754968

Transcriptional regulators transforming growth factor-beta 1 and estrogen-related receptor-alpha identified as putative mediators of calf rumen epithelial tissue development and function during weaning

USDA-ARS?s Scientific Manuscript database

Molecular mechanisms controlling rumen epithelial development at weaning remain largely unknown. To identify gene networks and regulatory factors responsive to concentrate versus forage feeding at weaning, Holstein bull calves (n = 18) were fed commercial milk replacer only (MRO) until 42 d of age. ...

Residential treatment for combat-related posttraumatic stress disorder: identifying trajectories of change and predictors of treatment response.

PubMed

Currier, Joseph M; Holland, Jason M; Drescher, Kent D

2014-01-01

Combat-related posttraumatic stress disorder (PTSD) can be a difficult condition to treat and has been associated with serious medical and economic issues among U.S. military veterans. Distinguishing between treatment responders vs. non-responders in this population has become an important public health priority. This study was conducted to identify pre-treatment characteristics of U.S. veterans with combat-related PTSD that might contribute to favorable and unfavorable responses to high value treatments for this condition. This study focused on 805 patients who completed a VHA PTSD residential program between 2000 and 2007. These patients completed the PTSD Clinical Checklist at pre-treatment, post-treatment, and a four-month follow-up assessment. Latent growth curve analysis (LCGA) was incorporated to determine trajectories of changes in PTSD across these assessments and whether several key clinical concerns for this population were associated with their treatment responses. LCGA indicated three distinct trajectories in PTSD outcomes and identified several clinical factors that were prospectively linked with changes in veterans' posttraumatic symptomatology. When compared to a group with high PTSD symptom severity that decreased over the program but relapsed at follow-up (41%), the near half (48.8%) of the sample with an improving trajectory had less combat exposure and superior physical/mental health. However, when compared to a minority (10.2%) with relatively low symptomatology that also remained somewhat stable, patients in the improving group were younger and also reported greater combat exposure, poorer physical/mental health status, and more problems with substance abuse before the start of treatment. Findings suggest that veterans are most likely to benefit from residential treatment in an intermediate range of symptoms and risk factors, including PTSD symptom severity, history of combat exposure, and comorbid issues with physical/mental health

Predictive factors for anemia response to erythropoiesis-stimulating agents in myelofibrosis.

PubMed

Hernández-Boluda, Juan-Carlos; Correa, Juan-Gonzalo; García-Delgado, Regina; Martínez-López, Joaquín; Alvarez-Larrán, Alberto; Fox, María-Laura; García-Gutiérrez, Valentín; Pérez-Encinas, Manuel; Ferrer-Marín, Francisca; Mata-Vázquez, María-Isabel; Raya, José-María; Estrada, Natalia; García, Silvia; Kerguelen, Ana; Durán, María-Antonia; Albors, Manuel; Cervantes, Francisco

2017-04-01

Erythropoiesis-stimulating agents (ESAs) are commonly used to treat the anemia of myelofibrosis (MF), but information on the predictors of response is limited. Results of ESA therapy were analyzed in 163 MF patients with severe anemia, most of whom had inadequate erythropoietin (EPO) levels (<125 U/L) at treatment start. According to the revised criteria of the International Working Group for Myelofibrosis Treatment and Research, anemia response was achieved in 86 patients (53%). Median response duration was 19.3 months. In multivariate analysis, baseline factors associated with a higher response rate were female sex (P=.007), leukocyte count ≥10×10 9 /L (P=.033), and serum ferritin <200 ng/mL (P=.002). Patients with 2 or 3 of the above features had a significantly higher response rate than the remainder (73% vs 28%, respectively; P<.001). Over the 373 patient-years of follow-up on ESA treatment, nine patients developed thrombotic complications (six arterial, three venous), accounting for 2.41 events per 100 patient-years. Survival time from ESA start was longer in anemia responders than in non-responders (P=.011). Besides the already established predictive value of EPO levels, these data can help to identify which MF patients are more likely to benefit from ESA treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

TimeXNet Web: Identifying cellular response networks from diverse omics time-course data.

PubMed

Tan, Phit Ling; López, Yosvany; Nakai, Kenta; Patil, Ashwini

2018-05-14

Condition-specific time-course omics profiles are frequently used to study cellular response to stimuli and identify associated signaling pathways. However, few online tools allow users to analyze multiple types of high-throughput time-course data. TimeXNet Web is a web server that extracts a time-dependent gene/protein response network from time-course transcriptomic, proteomic or phospho-proteomic data, and an input interaction network. It classifies the given genes/proteins into time-dependent groups based on the time of their highest activity and identifies the most probable paths connecting genes/proteins in consecutive groups. The response sub-network is enriched in activated genes/proteins and contains novel regulators that do not show any observable change in the input data. Users can view the resultant response network and analyze it for functional enrichment. TimeXNet Web supports the analysis of high-throughput data from multiple species by providing high quality, weighted protein-protein interaction networks for 12 model organisms. http://txnet.hgc.jp/. ashwini@hgc.jp. Supplementary data are available at Bioinformatics online.

The NAC transcription factor family in maritime pine (Pinus Pinaster): molecular regulation of two genes involved in stress responses.

PubMed

Pascual, Ma Belén; Cánovas, Francisco M; Ávila, Concepción

2015-10-24

NAC transcription factors comprise a large plant-specific gene family involved in the regulation of diverse biological processes. Despite the growing number of studies on NAC transcription factors in various species, little information is available about this family in conifers. The goal of this study was to identify the NAC transcription family in maritime pine (Pinus pinaster), to characterize ATAF-like genes in response to various stresses and to study their molecular regulation. We have isolated two maritime pine NAC genes and using a transient expression assay in N. benthamiana leaves estudied the promoter jasmonate response. In this study, we identified 37 NAC genes from maritime pine and classified them into six main subfamilies. The largest group includes 12 sequences corresponding to stress-related genes. Two of these NAC genes, PpNAC2 and PpNAC3, were isolated and their expression profiles were examined at various developmental stages and in response to various types of stress. The expression of both genes was strongly induced by methyl jasmonate (MeJA), mechanical wounding, and high salinity. The promoter regions of these genes were shown to contain cis-elements involved in the stress response and plant hormonal regulation, including E-boxes, which are commonly found in the promoters of genes that respond to jasmonate, and binding sites for bHLH proteins. Using a transient expression assay in N. benthamiana leaves, we found that the promoter of PpNAC3 was rapidly induced upon MeJA treatment, while this response disappeared in plants in which the transcription factor NbbHLH2 was silenced. Our results suggest that PpNAC2 and PpNAC3 encode stress-responsive NAC transcription factors involved in the jasmonate response in pine. Furthermore, these data also suggest that the jasmonate signaling pathway is conserved between angiosperms and gymnosperms. These findings may be useful for engineering stress tolerance in pine via biotechnological approaches.

Identifying attentional bias and emotional response after appearance-related stimuli exposure.

PubMed

Cho, Ara; Kwak, Soo-Min; Lee, Jang-Han

2013-01-01

The effect of media images has been regarded as a significant variable in the construction or in the activation of body images. Individuals who have a negative body image use avoidance coping strategies to minimize damage to their body image. We identified attentional biases and negative emotional responses following exposure to body stimuli. Female university students were divided into two groups based on their use of avoidance coping strategies (high-level group: high avoidance [HA]; low-group: low avoidance [LA]), and were assigned to two different conditions (exposure to thin body pictures, ET, and exposure to oversized body pictures, EO). Results showed that the HA group paid more attention to slim bodies and reported more negative emotions than the LA group, and that the EO had more negative effects than the ET. We suggest that HAs may attend more to slim bodies as a way of avoiding overweight bodies, influenced by social pressure, and in the search for a compensation of a positive emotional balance. However, attentional bias toward slim bodies can cause an upward comparison process, leading to increased body dissatisfaction, which is the main factor in the development of eating disorders (EDs). Therefore, altering avoidance coping strategies should be considered for people at risk of EDs.

Identifying mediating factors of moral reasoning in science education

NASA Astrophysics Data System (ADS)

Zeidler, Dana L.; Schafer, Larry E.

The purpose of this research was to examine how science content knowledge, moral reasoning ability, attitudes, and past experiences mediate the formation of moral judgments on environmental dilemmas. The study was conducted in two phases using environmental science majors and nonscience majors of college age. Phase One determined if environmental science majors exhibited higher levels of moral reasoning on nontechnical environmental social issues than on general social issues and examined the extent to which possible mediating factors accounted for differences in moral reasoning. Phase Two was qualitative in nature, the purpose of which was to observe and identify trends in conversations between subjects as to how certain mediating factors are revealed as people form moral judgments. The framework on which this study was constructed incorporates a progressive educational position; a position that views science education as being interdisciplinary, and a social means to a social end.

Risk factors associated with bovine trichomoniasis in beef cattle identified by a questionnaire.

PubMed

Jin, Yinzhu; Schumaker, Brant; Logan, Jim; Yao, Chaoqun

2014-06-01

Bovine trichomoniasis is a venereal disease that causes substantial economic losses to the cattle industry worldwide. It has been endemic in the USA since its discovery in the 1930s. The reasons for this long-lasting endemism are poorly understood. The main objective of this study was to identify herd-level risk factors for trichomoniasis in Wyoming beef cattle. A questionnaire was sent to all Wyoming beef cattle producers. The overall response proportion was 23.4 %. Questionnaires were returned from producers throughout the state in different geographical regions and with various herd sizes. In total, 863 questionnaires were analysed for correlation between the disease endemism and 25 variables. Tritrichomonas foetus infections were found to be significantly (P<0.05) associated with neighbouring a positive herd(s), grazing on public allotments and commingling with other herds. In addition, a delay in fixing broken fences approached statistical significance (P = 0.078). This study provides producers with valuable information and useful suggestions on how to effectively control and reduce the risks of bovine trichomoniasis. © 2014 The Authors.

Genome-Wide and Gene-Based Meta-Analyses Identify Novel Loci Influencing Blood Pressure Response to Hydrochlorothiazide.

PubMed

Salvi, Erika; Wang, Zhiying; Rizzi, Federica; Gong, Yan; McDonough, Caitrin W; Padmanabhan, Sandosh; Hiltunen, Timo P; Lanzani, Chiara; Zaninello, Roberta; Chittani, Martina; Bailey, Kent R; Sarin, Antti-Pekka; Barcella, Matteo; Melander, Olle; Chapman, Arlene B; Manunta, Paolo; Kontula, Kimmo K; Glorioso, Nicola; Cusi, Daniele; Dominiczak, Anna F; Johnson, Julie A; Barlassina, Cristina; Boerwinkle, Eric; Cooper-DeHoff, Rhonda M; Turner, Stephen T

2017-01-01

This study aimed to identify novel loci influencing the antihypertensive response to hydrochlorothiazide monotherapy. A genome-wide meta-analysis of blood pressure (BP) response to hydrochlorothiazide was performed in 1739 white hypertensives from 6 clinical trials within the International Consortium for Antihypertensive Pharmacogenomics Studies, making it the largest study to date of its kind. No signals reached genome-wide significance (P<5×10 - 8 ), and the suggestive regions (P<10 -5 ) were cross-validated in 2 black cohorts treated with hydrochlorothiazide. In addition, a gene-based analysis was performed on candidate genes with previous evidence of involvement in diuretic response, in BP regulation, or in hypertension susceptibility. Using the genome-wide meta-analysis approach, with validation in blacks, we identified 2 suggestive regulatory regions linked to gap junction protein α1 gene (GJA1) and forkhead box A1 gene (FOXA1), relevant for cardiovascular and kidney function. With the gene-based approach, we identified hydroxy-delta-5-steroid dehydrogenase, 3 β- and steroid δ-isomerase 1 gene (HSD3B1) as significantly associated with BP response (P<2.28×10 - 4 ). HSD3B1 encodes the 3β-hydroxysteroid dehydrogenase enzyme and plays a crucial role in the biosynthesis of aldosterone and endogenous ouabain. By amassing all of the available pharmacogenomic studies of BP response to hydrochlorothiazide, and using 2 different analytic approaches, we identified 3 novel loci influencing BP response to hydrochlorothiazide. The gene-based analysis, never before applied to pharmacogenomics of antihypertensive drugs to our knowledge, provided a powerful strategy to identify a locus of interest, which was not identified in the genome-wide meta-analysis because of high allelic heterogeneity. These data pave the way for future investigations on new pathways and drug targets to enhance the current understanding of personalized antihypertensive treatment. © 2016

Using decision tree analysis to identify risk factors for relapse to smoking

PubMed Central

Piper, Megan E.; Loh, Wei-Yin; Smith, Stevens S.; Japuntich, Sandra J.; Baker, Timothy B.

2010-01-01

This research used classification tree analysis and logistic regression models to identify risk factors related to short- and long-term abstinence. Baseline and cessation outcome data from two smoking cessation trials, conducted from 2001 to 2002, in two Midwestern urban areas, were analyzed. There were 928 participants (53.1% women, 81.8% white) with complete data. Both analyses suggest that relapse risk is produced by interactions of risk factors and that early and late cessation outcomes reflect different vulnerability factors. The results illustrate the dynamic nature of relapse risk and suggest the importance of efficient modeling of interactions in relapse prediction. PMID:20397871

Vibrio cholerae ToxR downregulates virulence factor production in response to cyclo(Phe-Pro).

PubMed

Bina, X Renee; Taylor, Dawn L; Vikram, Amit; Ante, Vanessa M; Bina, James E

2013-08-27

Vibrio cholerae is an aquatic organism that causes the severe acute diarrheal disease cholera. The ability of V. cholerae to cause disease is dependent upon the production of two critical virulence determinants, cholera toxin (CT) and the toxin-coregulated pilus (TCP). The expression of the genes that encode for CT and TCP production is under the control of a hierarchical regulatory system called the ToxR regulon, which functions to activate virulence gene expression in response to in vivo stimuli. Cyclic dipeptides have been found to be produced by numerous bacteria, yet their biological function remains unknown. V. cholerae has been shown to produce cyclo(Phe-Pro). Previous studies in our laboratory demonstrated that cyclo(Phe-Pro) inhibited V. cholerae virulence factor production. For this study, we report on the mechanism by which cyclo(Phe-Pro) inhibited virulence factor production. We have demonstrated that exogenous cyclo(Phe-Pro) activated the expression of leuO, a LysR-family regulator that had not been previously associated with V. cholerae virulence. Increased leuO expression repressed aphA transcription, which resulted in downregulation of the ToxR regulon and attenuated CT and TCP production. The cyclo(Phe-Pro)-dependent induction of leuO expression was found to be dependent upon the virulence regulator ToxR. Cyclo(Phe-Pro) did not affect toxR transcription or ToxR protein levels but appeared to enhance the ToxR-dependent transcription of leuO. These results have identified leuO as a new component of the ToxR regulon and demonstrate for the first time that ToxR is capable of downregulating virulence gene expression in response to an environmental cue. The ToxR regulon has been a focus of cholera research for more than three decades. During this time, a model has emerged wherein ToxR functions to activate the expression of Vibrio cholerae virulence factors upon host entry. V. cholerae and other enteric bacteria produce cyclo(Phe-Pro), a cyclic dipeptide

Interacting TCP and NLP transcription factors control plant responses to nitrate availability.

PubMed

Guan, Peizhu; Ripoll, Juan-José; Wang, Renhou; Vuong, Lam; Bailey-Steinitz, Lindsay J; Ye, Dening; Crawford, Nigel M

2017-02-28

Plants have evolved adaptive strategies that involve transcriptional networks to cope with and survive environmental challenges. Key transcriptional regulators that mediate responses to environmental fluctuations in nitrate have been identified; however, little is known about how these regulators interact to orchestrate nitrogen (N) responses and cell-cycle regulation. Here we report that teosinte branched1/cycloidea/proliferating cell factor1-20 (TCP20) and NIN-like protein (NLP) transcription factors NLP6 and NLP7, which act as activators of nitrate assimilatory genes, bind to adjacent sites in the upstream promoter region of the nitrate reductase gene, NIA1 , and physically interact under continuous nitrate and N-starvation conditions. Regions of these proteins necessary for these interactions were found to include the type I/II Phox and Bem1p (PB1) domains of NLP6&7, a protein-interaction module conserved in animals for nutrient signaling, and the histidine- and glutamine-rich domain of TCP20, which is conserved across plant species. Under N starvation, TCP20-NLP6&7 heterodimers accumulate in the nucleus, and this coincides with TCP20 and NLP6&7-dependent up-regulation of nitrate assimilation and signaling genes and down-regulation of the G 2 /M cell-cycle marker gene, CYCB1;1 TCP20 and NLP6&7 also support root meristem growth under N starvation. These findings provide insights into how plants coordinate responses to nitrate availability, linking nitrate assimilation and signaling with cell-cycle progression.

Identifying and Investigating Unexpected Response to Treatment: A Diabetes Case Study.

PubMed

Ozery-Flato, Michal; Ein-Dor, Liat; Parush-Shear-Yashuv, Naama; Aharonov, Ranit; Neuvirth, Hani; Kohn, Martin S; Hu, Jianying

2016-09-01

The availability of electronic health records creates fertile ground for developing computational models of various medical conditions. We present a new approach for detecting and analyzing patients with unexpected responses to treatment, building on machine learning and statistical methodology. Given a specific patient, we compute a statistical score for the deviation of the patient's response from responses observed in other patients having similar characteristics and medication regimens. These scores are used to define cohorts of patients showing deviant responses. Statistical tests are then applied to identify clinical features that correlate with these cohorts. We implement this methodology in a tool that is designed to assist researchers in the pharmaceutical field to uncover new features associated with reduced response to a treatment. It can also aid physicians by flagging patients who are not responding to treatment as expected and hence deserve more attention. The tool provides comprehensive visualizations of the analysis results and the supporting data, both at the cohort level and at the level of individual patients. We demonstrate the utility of our methodology and tool in a population of type II diabetic patients, treated with antidiabetic drugs, and monitored by the HbA1C test.

Assessment of seismic design response factors of concrete wall buildings

NASA Astrophysics Data System (ADS)

Mwafy, Aman

2011-03-01

To verify the seismic design response factors of high-rise buildings, five reference structures, varying in height from 20- to 60-stories, were selected and designed according to modern design codes to represent a wide range of concrete wall structures. Verified fiber-based analytical models for inelastic simulation were developed, considering the geometric nonlinearity and material inelasticity of the structural members. The ground motion uncertainty was accounted for by employing 20 earthquake records representing two seismic scenarios, consistent with the latest understanding of the tectonic setting and seismicity of the selected reference region (UAE). A large number of Inelastic Pushover Analyses (IPAs) and Incremental Dynamic Collapse Analyses (IDCAs) were deployed for the reference structures to estimate the seismic design response factors. It is concluded that the factors adopted by the design code are adequately conservative. The results of this systematic assessment of seismic design response factors apply to a wide variety of contemporary concrete wall buildings with various characteristics.

Identifying and reducing risk factors related to trainee-client sexual misconduct.

PubMed

Hamilton, J C; Spruill, J

1999-06-01

Sexual misconduct involving therapists-in-training and their clients is addressed. Personal and situational factors that may constitute risk factors for the development of inappropriate sexual activity between trainees and their clients are identified. Although there may be certain characteristics that put particular students at risk for such involvement, the authors believe this risk is more strongly related to systemic, programmatic, and pedagogic characteristics of the environments in which students train. Examples include, respectively, the decline of concern over transference and countertransference, failure to include education about client-therapist sexual attraction and the consequences of sexual misconduct in graduate psychology curricula, and the reluctance of supervisors to deal straightforwardly with trainees' sexual feelings. Suggestions for reducing risks for client-therapist sexual misconduct are directed toward these situational factors.

Nightmares in the general population: identifying potential causal factors.

PubMed

Rek, Stephanie; Sheaves, Bryony; Freeman, Daniel

2017-09-01

Nightmares are inherently distressing, prevent restorative sleep, and are associated with a number of psychiatric problems, but have rarely been the subject of empirical study. Negative affect, linked to stressful events, is generally considered the key trigger of nightmares; hence nightmares have most often been considered in the context of post-traumatic stress disorder (PTSD). However, many individuals with heightened negative affect do not have nightmares. The objective of this study was to identify mechanistically plausible factors, beyond negative affect, that may explain why individuals experience nightmares. 846 participants from the UK general population completed an online survey about nightmare occurrence and severity (pre-occupation, distress, and impairment), negative affect, worry, depersonalisation, hallucinatory experiences, paranoia, alcohol use, sleep duration, physical activity levels, PTSD symptoms, and stressful life events. Associations of nightmares with the putative predictive factors were tested controlling for levels of negative affect. Analyses were also repeated controlling for levels of PTSD and the recent occurrence of stressful life events. Nightmare occurrence, adjusting for negative affect, was associated with higher levels of worry, depersonalisation, hallucinatory experiences, paranoia, and sleep duration (odds ratios 1.25-1.45). Nightmare severity, controlling for negative affect, was associated with higher levels of worry, depersonalisation, hallucinatory experiences, and paranoia (R 2 s: 0.33-0.39). Alcohol use and physical activity levels were not associated with nightmares. The study identifies a number of potential predictors of the occurrence and severity of nightmares. Causal roles require testing in future longitudinal, experimental, and treatment studies.

Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis

PubMed Central

Malhotra, Deepti; Portales-Casamar, Elodie; Singh, Anju; Srivastava, Siddhartha; Arenillas, David; Happel, Christine; Shyr, Casper; Wakabayashi, Nobunao; Kensler, Thomas W.; Wasserman, Wyeth W.; Biswal, Shyam

2010-01-01

The Nrf2 (nuclear factor E2 p45-related factor 2) transcription factor responds to diverse oxidative and electrophilic environmental stresses by circumventing repression by Keap1, translocating to the nucleus, and activating cytoprotective genes. Nrf2 responses provide protection against chemical carcinogenesis, chronic inflammation, neurodegeneration, emphysema, asthma and sepsis in murine models. Nrf2 regulates the expression of a plethora of genes that detoxify oxidants and electrophiles and repair or remove damaged macromolecules, such as through proteasomal processing. However, many direct targets of Nrf2 remain undefined. Here, mouse embryonic fibroblasts (MEF) with either constitutive nuclear accumulation (Keap1−/−) or depletion (Nrf2−/−) of Nrf2 were utilized to perform chromatin-immunoprecipitation with parallel sequencing (ChIP-Seq) and global transcription profiling. This unique Nrf2 ChIP-Seq dataset is highly enriched for Nrf2-binding motifs. Integrating ChIP-Seq and microarray analyses, we identified 645 basal and 654 inducible direct targets of Nrf2, with 244 genes at the intersection. Modulated pathways in stress response and cell proliferation distinguish the inducible and basal programs. Results were confirmed in an in vivo stress model of cigarette smoke-exposed mice. This study reveals global circuitry of the Nrf2 stress response emphasizing Nrf2 as a central node in cell survival response. PMID:20460467

41 CFR 102-80.50 - Are Federal agencies responsible for identifying/estimating risks and for appropriate risk...

Code of Federal Regulations, 2010 CFR

2010-07-01

... identify and estimate safety and environmental management risks and appropriate risk reduction strategies... responsible for identifying/estimating risks and for appropriate risk reduction strategies? 102-80.50 Section... Environmental Management Risks and Risk Reduction Strategies § 102-80.50 Are Federal agencies responsible for...

Factors associated with differential response to online cognitive behavioural therapy.

PubMed

Button, Katherine S; Wiles, Nicola J; Lewis, Glyn; Peters, Tim J; Kessler, David

2012-05-01

Patients differ in their response to treatments. There is obvious clinical utility in establishing patient characteristics that are associated with differential treatment responses (i.e., are effect modifiers or moderators of treatment response). Factors that moderate response to cognitive behavioural therapy (CBT) remain unclear. This study investigates whether factors prognostic of general depression outcome generally are also moderators of response to online CBT in a sample of depressed patients recruited through U.K. general practices. Secondary analysis of a randomised controlled trial, internet-based psychotherapy for depression. A total of 297 patients referred from 55 U.K. general practices and suffering from depression were randomly allocated to receive either online CBT or waiting list control. Treatment effect was measured by comparing depression score at 4 months between randomization groups. Treatment effect modification was assessed using regression analyses focusing on interactions between treatment effect and putative moderator variables. Pretreatment severity and marital status moderated treatment response. More severe patients, and patients who were separated, widowed, or divorced, benefited most from the intervention. Weak evidence suggested that treatment effectiveness diminished with increasing recent adverse life events. No evidence was found to suggest that educational attainment, age, and history of depression-moderated treatment response. Secondary analyses of trials comparing two or more treatments allow factors that may moderate treatment response to be distinguished from more general prognostic indicators, although caution is needed in interpreting such exploratory analyses.

Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators

NASA Technical Reports Server (NTRS)

Belaguli, N. S.; Sepulveda, J. L.; Nigam, V.; Charron, F.; Nemer, M.; Schwartz, R. J.

2000-01-01

Combinatorial interaction among cardiac tissue-restricted enriched transcription factors may facilitate the expression of cardiac tissue-restricted genes. Here we show that the MADS box factor serum response factor (SRF) cooperates with the zinc finger protein GATA-4 to synergistically activate numerous myogenic and nonmyogenic serum response element (SRE)-dependent promoters in CV1 fibroblasts. In the absence of GATA binding sites, synergistic activation depends on binding of SRF to the proximal CArG box sequence in the cardiac and skeletal alpha-actin promoter. GATA-4's C-terminal activation domain is obligatory for synergistic coactivation with SRF, and its N-terminal domain and first zinc finger are inhibitory. SRF and GATA-4 physically associate both in vivo and in vitro through their MADS box and the second zinc finger domains as determined by protein A pullout assays and by in vivo one-hybrid transfection assays using Gal4 fusion proteins. Other cardiovascular tissue-restricted GATA factors, such as GATA-5 and GATA-6, were equivalent to GATA-4 in coactivating SRE-dependent targets. Thus, interaction between the MADS box and C4 zinc finger proteins, a novel regulatory paradigm, mediates activation of SRF-dependent gene expression.

Toxicokinetics to identify nonlinearities in dose-response and implications for risk assessment

EPA Science Inventory

For presentation at the 45th Annual Symposium of the Society of Toxicology of Canada. The meeting will be held on 4-5 December 2013 at the Ottawa Convention Centre. Toxicokinetics to identify nonlinearities in dose-response and implications for risk assessment. Rory Conolly, Offi...

Using high frequency consumption data to identify demand response potential for solar energy integration

NASA Astrophysics Data System (ADS)

Jin, L.; Borgeson, S.; Fredman, D.; Hans, L.; Spurlock, A.; Todd, A.

2015-12-01

California's renewable portfolio standard (2012) requires the state to get 33% of its electricity from renewable sources by 2020. Increased share of variable renewable sources such as solar and wind in the California electricity system may require more grid flexibility to insure reliable power services. Such grid flexibility can be potentially provided by changes in end use electricity consumptions in response to grid conditions (demand-response). In the solar case, residential consumption in the late afternoon can be used as reserve capacity to balance the drop in solar generation. This study presents our initial attempt to identify, from a behavior perspective, residential demand response potentials in relation to solar ramp events using a data-driven approach. Based on hourly residential energy consumption data, we derive representative daily load shapes focusing on discretionary consumption with an innovative clustering analysis technique. We aggregate the representative load shapes into behavior groups in terms of the timing and rhythm of energy use in the context of solar ramp events. Households of different behavior groups that are active during hours with high solar ramp rates are identified for capturing demand response potential. Insights into the nature and predictability of response to demand-response programs are provided.

Legionella: virulence factors and host response.

PubMed

Misch, Elizabeth Ann

2016-06-01

Legionella pneumophila is a facultative intracellular pathogen and an important cause of community-acquired and nosocomial pneumonia. This review focuses on the latest literature examining Legionella's virulence strategies and the mammalian host response. Recent studies identify novel virulence strategies used by L. pneumophila and new aspects of the host immune response to this pathogen. Legionella prevents acidification of the phagosome by recruiting Rab1, a host protein. Legionella also blocks a conserved endoplasmic reticulum stress response. To access iron from host stores, L. pneumophila upregulates more regions allowing vacuolar colocalization N. In response to Legionella, the host cell may activate caspase-1, caspase-11 (mice) or caspase-4 (humans). Caspase-3 and apoptosis are activated by a secreted, bacterial effector. Infected cells send signals to their uninfected neighbors, allowing the elaboration of inflammatory cytokines in trans. Antibody subclasses provide robust protection against Legionella. L. pneumophila is a significant human pathogen that lives in amoebae in the environment but may opportunistically infect the alveolar macrophage. To maintain its intracellular lifestyle, Legionella extracts essential iron from the cell, blocks inflammatory responses and manipulates trafficking to avoid fusion with the lysosome. The mammalian host has counter strategies, which include the release of proinflammatory cytokines, the activation of caspases and antibody-mediated immunity.

[Cryptogenic West syndrome: Clinical profile, response to treatment and prognostic factors].

PubMed

Calderón Romero, María; Arce Portillo, Elena; López Lobato, Mercedes; Muñoz Cabello, Beatriz; Blanco Martínez, Bárbara; Madruga Garrido, Marcos; Alonso Luego, Olga

2017-12-06

West syndrome (WS) is an age-dependent epileptic encephalopathy in which the prognosis varies according to the, not always identified, underlying origin. To define the profile of cryptogenic (a least studied isolated sub-group) WS, in Spain. To study its outcome, response to different treatments, and to establish prognostic factors. The study included a review of the medical records of 16 patients diagnosed with cryptogenic WS during the period, 2000-2015. The mean follow-up time was 6.6 years, with a minimum of 2 years. The large majority (11/16) were male. The mean age at onset was 6 months, and 6/16 had a family history of idiopathic epilepsy. The first line treatment with vigabatrin had an electrical-clinical response in 5/16 patients, with the remaining cases responding to adrenocorticotropic hormone (ACTH). Almost half (44%) of the patients progressed to other types of epilepsy, with no difference between those treated with vigabatrin or ACTH. A greater number of adverse effects were obtained with ACTH, with no retinal involvement being observed with vigabatrin. The aetiological cause was found in 2/16. Being female, late onset, and early control of the hypsarrhythmia, were factors of a good prognosis. The overall prognosis of cryptogenic WS was more serious than expected. Although the incidence of Lennox-Gastaut syndrome was low, the progression to focal epilepsy was the most common, with it appearing within the first 2 years of the diagnosis. The initial response to vigabatrin was lower than expected, but the long-term result was comparable to ACTH. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Identifying and exploring factors influencing career choice, recruitment and retention of anaesthesia trainees in the UK.

PubMed

Moore, J N; McDiarmid, A J; Johnston, P W; Cleland, J A

2017-02-01

Many acute hospital specialties are experiencing low recruitment and high attrition of trainees. Understanding what is important to current trainees is critical in terms of identifying and addressing factors which adversely affect recruitment and retention. To identify and explore factors involved in anaesthetic trainees' career decision making. This was a mixed methods study using a questionnaire survey (assessing how influential 18 different factors were when choosing anaesthetics, using a five-point Likert scale), supplemented by semi-structured interviews, carried out in August-December 2014, in Scotland, UK. 42/68 (62%) completed responses were received, representing over half of all core (58%) and Acute Care Common Stem (65%) trainees across Scotland. Overall, questionnaire data indicated that the following were most important in career decision making: perceived job satisfaction among those already in the specialty, structured training, the nature of the work (practical, varied, immediate outcomes). Thirteen interviews were carried out. These highlighted that prior positive exposure and experience with anaesthetists encouraged trainees into the specialty. Enthusiastic, supportive colleagues and structured training (including clear milestones, regular teaching and feedback) were considered to enhance the quality of training. Sustainable working conditions, flexibility within programme and out-of-programme opportunities were valued. Respondents reported concerns about the impact of increasing service delivery demands on training quality. Many of the elements important to today's anaesthetics trainees are related to positive learning and working environments. This fits with research findings from other professional groups. These findings can inform the development of programmes which cultivate trainee commitment to, and enthusiasm for, anaesthetics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

An Alternative σ Factor, σ8, Controls Avermectin Production and Multiple Stress Responses in Streptomyces avermitilis.

PubMed

Sun, Di; Wang, Qian; Chen, Zhi; Li, Jilun; Wen, Ying

2017-01-01

Alternative σ factors in bacteria redirect RNA polymerase to recognize alternative promoters, thereby facilitating coordinated gene expression necessary for adaptive responses. The gene sig8 ( sav_741 ) in Streptomyces avermitilis encodes an alternative σ factor, σ 8 , highly homologous to σ B in Streptomyces coelicolor . Studies reported here demonstrate that σ 8 is an important regulator of both avermectin production and stress responses in S. avermitilis . σ 8 inhibited avermectin production by indirectly repressing expression of cluster-situated activator gene aveR , and by directly initiating transcription of its downstream gene sav_742 , which encodes a direct repressor of ave structural genes. σ 8 had no effect on cell growth or morphological differentiation under normal growth conditions. Growth of a sig8- deletion mutant was less than that of wild-type strain on YMS plates following treatment with heat, H 2 O 2 , diamide, NaCl, or KCl. sig8 transcription was strongly induced by these environmental stresses, indicating response by σ 8 itself. A series of σ 8 -dependent genes responsive to heat, oxidative and osmotic stress were identified by EMSAs, qRT-PCR and in vitro transcription experiments. These findings indicate that σ 8 plays an important role in mediating protective responses to various stress conditions by activating transcription of its target genes. Six σ 8 -binding promoter sequences were determined and consensus binding sequence BGVNVH-N 15 -GSNNHH (B: C, T or G, V: A, C or G, S: C or G, H: A, C or T, N: any nucleotide) was identified, leading to prediction of the σ 8 regulon. The list consists of 940 putative σ 8 target genes, assignable to 17 functional groups, suggesting the wide range of cellular functions controlled by σ 8 in S. avermitilis .

Hospital Readmission and Social Risk Factors Identified from Physician Notes.

PubMed

Navathe, Amol S; Zhong, Feiran; Lei, Victor J; Chang, Frank Y; Sordo, Margarita; Topaz, Maxim; Navathe, Shamkant B; Rocha, Roberto A; Zhou, Li

2018-04-01

To evaluate the prevalence of seven social factors using physician notes as compared to claims and structured electronic health records (EHRs) data and the resulting association with 30-day readmissions. A multihospital academic health system in southeastern Massachusetts. An observational study of 49,319 patients with cardiovascular disease admitted from January 1, 2011, to December 31, 2013, using multivariable logistic regression to adjust for patient characteristics. All-payer claims, EHR data, and physician notes extracted from a centralized clinical registry. All seven social characteristics were identified at the highest rates in physician notes. For example, we identified 14,872 patient admissions with poor social support in physician notes, increasing the prevalence from 0.4 percent using ICD-9 codes and structured EHR data to 16.0 percent. Compared to an 18.6 percent baseline readmission rate, risk-adjusted analysis showed higher readmission risk for patients with housing instability (readmission rate 24.5 percent; p < .001), depression (20.6 percent; p < .001), drug abuse (20.2 percent; p = .01), and poor social support (20.0 percent; p = .01). The seven social risk factors studied are substantially more prevalent than represented in administrative data. Automated methods for analyzing physician notes may enable better identification of patients with social needs. © Health Research and Educational Trust.

Elevated Peritoneal Fluid TNF-α Incites Ovarian Early Growth Response Factor 1 Expression and Downstream Protease Mediators

PubMed Central

Birt, Julie A.; Nabli, Henda; Stilley, Julie A.; Windham, Emma A.; Frazier, Shellaine R.

2013-01-01

Endometriosis-associated infertility manifests itself via multiple, poorly understood mechanisms. Our goal was to characterize signaling pathways, between peritoneal endometriotic lesions and the ovary, leading to failed ovulation. Genome-wide microarray analysis comparing ovarian tissue from an in vivo endometriosis model in the rat (Endo) with controls (Sham) identified 22 differentially expressed genes, including transiently expressed early growth response factor 1 (Egr1). The Egr1 regulates gene requisites for ovulation. The Egr1 promoter is responsive to tumor necrosis factor-alpha (TNF-α) signaling. We hypothesized that altered expression of ovarian EGR1 is induced by elevated peritoneal fluid TNF-α which is upregulated by the presence of peritoneal endometriosis. Endo rats, compared to controls, had more peritoneal fluid TNF-α and quantitative, spatial differences in Egr1 mRNA and EGR1 protein localization in follicular compartments. Interactions between elevated peritoneal fluid TNF-α and overexpression of follicular Egr1/EGR1 expression may affect downstream protease pathways impeding ovulation in endometriosis. Preliminary studies identified similar patterns of EGR1 protein localization in human ovaries from women with endometriosis and compared to those without endometriosis. PMID:23427178

MYC Amplification as a Predictive Factor of Complete Pathologic Response to Docetaxel-based Neoadjuvant Chemotherapy for Breast Cancer.

PubMed

Pereira, Cynthia Brito Lins; Leal, Mariana Ferreira; Abdelhay, Eliana Saul Furquim Werneck; Demachki, Sâmia; Assumpção, Paulo Pimentel; de Souza, Mirian Carvalho; Moreira-Nunes, Caroline Aquino; Tanaka, Adriana Michiko da Silva; Smith, Marília Cardoso; Burbano, Rommel Rodríguez

2017-06-01

Neoadjuvant chemotherapy is a standard treatment for stage II and III breast cancer. The identification of biomarkers that may help in the prediction of response to neoadjuvant therapies is necessary for a more precise definition of the best drug or drug combination to induce a better response. We assessed the role of Ki67, hormone receptors expression, HER2, MYC genes and their protein status, and KRAS codon 12 mutations as predictor factors of pathologic response to anthracycline-cyclophosphamide (AC) followed by taxane docetaxel (T) neoadjuvant chemotherapy (AC+T regimen) in 51 patients with invasive ductal breast cancer. After neoadjuvant chemotherapy, 82.4% of patients showed pathologic partial response, with only 9.8% showing pathologic complete response. In multivariate analysis, MYC immunoreactivity and high MYC gain defined as MYC/nucleus ≥ 5 were significant predictor factors for pathologic partial response. Using the receiver operating characteristic curve analysis, the ratio of 2.5 MYC/CEP8 (sensitivity of 80% and specificity of 89.1%) or 7 MYC/nuclei copies (sensitivity of 80% and specificity of 73.9%) as the best cutoff in predicting a pathologic complete response was identified. Thus, MYC may have a role in chemosensitivity to AC and/or docetaxel drugs. Additionally, MYC amplification may be a predictor factor of pathologic response to the AC+T regimen in patients with breast cancer. Moreover, patients with an increased number of MYC copies showed pathologic complete response to this neoadjuvant treatment more frequently. The analysis of MYC amplification may help in the identification of patients that may have a better response to AC+T treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Identifying items to assess methodological quality in physical therapy trials: a factor analysis.

PubMed

Armijo-Olivo, Susan; Cummings, Greta G; Fuentes, Jorge; Saltaji, Humam; Ha, Christine; Chisholm, Annabritt; Pasichnyk, Dion; Rogers, Todd

2014-09-01

Numerous tools and individual items have been proposed to assess the methodological quality of randomized controlled trials (RCTs). The frequency of use of these items varies according to health area, which suggests a lack of agreement regarding their relevance to trial quality or risk of bias. The objectives of this study were: (1) to identify the underlying component structure of items and (2) to determine relevant items to evaluate the quality and risk of bias of trials in physical therapy by using an exploratory factor analysis (EFA). A methodological research design was used, and an EFA was performed. Randomized controlled trials used for this study were randomly selected from searches of the Cochrane Database of Systematic Reviews. Two reviewers used 45 items gathered from 7 different quality tools to assess the methodological quality of the RCTs. An exploratory factor analysis was conducted using the principal axis factoring (PAF) method followed by varimax rotation. Principal axis factoring identified 34 items loaded on 9 common factors: (1) selection bias; (2) performance and detection bias; (3) eligibility, intervention details, and description of outcome measures; (4) psychometric properties of the main outcome; (5) contamination and adherence to treatment; (6) attrition bias; (7) data analysis; (8) sample size; and (9) control and placebo adequacy. Because of the exploratory nature of the results, a confirmatory factor analysis is needed to validate this model. To the authors' knowledge, this is the first factor analysis to explore the underlying component items used to evaluate the methodological quality or risk of bias of RCTs in physical therapy. The items and factors represent a starting point for evaluating the methodological quality and risk of bias in physical therapy trials. Empirical evidence of the association among these items with treatment effects and a confirmatory factor analysis of these results are needed to validate these items. �

Identifying and prioritizing industry-level competitiveness factors: evidence from pharmaceutical market

PubMed Central

2014-01-01

Background Pharmaceutical industry is knowledge-intensive and highly globalized, in both developed and developing countries. On the other hand, if companies want to survive, they should be able to compete well in both domestic and international markets. The main purpose of this paper is therefore to develop and prioritize key factors affecting companies’ competitiveness in pharmaceutical industry. Based on an extensive literature review, a valid and reliable questionnaire was designed, which was later filled up by participants from the industry. To prioritize the key factors, we used the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS). Results The results revealed that human capital and macro-level policies were two key factors placed at the highest rank in respect of their effects on the competitiveness considering the industry-level in pharmaceutical area. Conclusion This study provides fundamental evidence for policymakers and managers in pharma context to enable them formulating better polices to be proactively competitive and responsive to the markets’ needs. PMID:24708770

Identifying and prioritizing industry-level competitiveness factors: evidence from pharmaceutical market.

PubMed

Shabaninejad, Hosein; Mehralian, Gholamhossein; Rashidian, Arash; Baratimarnani, Ahmad; Rasekh, Hamid Reza

2014-04-03

Pharmaceutical industry is knowledge-intensive and highly globalized, in both developed and developing countries. On the other hand, if companies want to survive, they should be able to compete well in both domestic and international markets. The main purpose of this paper is therefore to develop and prioritize key factors affecting companies' competitiveness in pharmaceutical industry. Based on an extensive literature review, a valid and reliable questionnaire was designed, which was later filled up by participants from the industry. To prioritize the key factors, we used the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS). The results revealed that human capital and macro-level policies were two key factors placed at the highest rank in respect of their effects on the competitiveness considering the industry-level in pharmaceutical area. This study provides fundamental evidence for policymakers and managers in pharma context to enable them formulating better polices to be proactively competitive and responsive to the markets' needs.

Identifying Predictors, Moderators, and Mediators of Antidepressant Response in Major Depressive Disorder: Neuroimaging Approaches

PubMed Central

Phillips, Mary L.; Chase, Henry W.; Sheline, Yvette I.; Etkin, Amit; Almeida, Jorge R.C.; Deckersbach, Thilo; Trivedi, Madhukar H.

2015-01-01

Objective Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. Method In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. Results The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Conclusions Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes. PMID:25640931

Ethylene Response Factors Are Controlled by Multiple Harvesting Stresses in Hevea brasiliensis

PubMed Central

Putranto, Riza-Arief; Duan, Cuifang; Kuswanhadi; Chaidamsari, Tetty; Rio, Maryannick; Piyatrakul, Piyanuch; Herlinawati, Eva; Pirrello, Julien; Dessailly, Florence; Leclercq, Julie; Bonnot, François; Tang, Chaorong; Hu, Songnian; Montoro, Pascal

2015-01-01

Tolerance of recurrent mechanical wounding and exogenous ethylene is a feature of the rubber tree. Latex harvesting involves tapping of the tree bark and ethephon is applied to increase latex flow. Ethylene is an essential element in controlling latex production. The ethylene signalling pathway leads to the activation of Ethylene Response Factor (ERF) transcription factors. This family has been identified in Hevea brasiliensis. This study set out to understand the regulation of ERF genes during latex harvesting in relation to abiotic stress and hormonal treatments. Analyses of the relative transcript abundance were carried out for 35 HbERF genes in latex, in bark from mature trees and in leaves from juvenile plants under multiple abiotic stresses. Twenty-one HbERF genes were regulated by harvesting stress in laticifers, revealing an overrepresentation of genes in group IX. Transcripts of three HbERF-IX genes from HbERF-IXc4, HbERF-IXc5 and HbERF-IXc6 were dramatically accumulated by combining wounding, methyl jasmonate and ethylene treatments. When an ethylene inhibitor was used, the transcript accumulation for these three genes was halted, showing ethylene-dependent induction. Subcellular localization and transactivation experiments confirmed that several members of HbERF-IX are activator-type transcription factors. This study suggested that latex harvesting induces mechanisms developed for the response to abiotic stress. These mechanisms probably depend on various hormonal signalling pathways. Several members of HbERF-IX could be essential integrators of complex hormonal signalling pathways in Hevea. PMID:25906196

Identifying depressive symptom trajectory groups among Korean adults and psychosocial factors as group determinants.

PubMed

Kwon, Tae Yeon

2015-06-01

Longitudinal research is needed to examine the depressive symptom trajectories of different groups during adulthood and their antecedents and consequences, because depressive symptoms may be changeable and heterogeneous over time. This study examined the number of trajectory groups describing the depressive symptoms of Korean adults, as well as the shape of the trajectories and the association between trajectory group membership and psychosocial factors identified based on the ecosystem model. This study used Nagin's semi-parametric group-based modeling to analyze Year 1 to Year 7 data from Korea Welfare Panel Survey (N = 13,735), a nationally representative sample of community-dwelling adults. Three distinct trajectory groups were identified: a low stable depressive symptoms group, a moderate depressive symptoms group and a high depressive symptoms group. Result from multinominal logit analysis showed that all psychosocial factors except family relationships affected the likelihood of membership in the three depressive symptoms groups. Especially, self-esteem was the psychosocial factor with the largest impact on depressive symptom trajectory group membership. When screening for depressive symptoms, individuals with a low socioeconomic status should be a primary concern and intervention should be made available to them. Prevention or intervention with members of the identified trajectory groups would likely require integrative approaches targeting psychosocial factors across multiple contexts. © The Author(s) 2015.

A genetic screen in Myxococcus xanthus identifies mutants that uncouple outer membrane exchange from a downstream cellular response.

PubMed

Dey, Arup; Wall, Daniel

2014-12-01

Upon physical contact with sibling cells, myxobacteria transiently fuse their outer membranes (OMs) and exchange OM proteins and lipids. From previous work, TraA and TraB were identified to be essential factors for OM exchange (OME) in donor and recipient cells. To define the genetic complexity of OME, we carried out a comprehensive forward genetic screen. The screen was based on the observation that Myxococcus xanthus nonmotile cells, by a Tra-dependent mechanism, block swarm expansion of motile cells when mixed. Thus, mutants defective in OME or a downstream responsive pathway were readily identified as escape flares from mixed inocula seeded on agar. This screen was surprisingly powerful, as we found >50 mutants defective in OME. Importantly, all of the mutations mapped to the traAB operon, suggesting that there may be few, if any, proteins besides TraA and TraB directly required for OME. We also found a second and phenotypically different class of mutants that exhibited wild-type OME but were defective in a responsive pathway. This pathway is postulated to control inner membrane homeostasis by covalently attaching amino acids to phospholipids. The identified proteins are homologous to the Staphylococcus aureus MprF protein, which is involved in membrane adaptation and antibiotic resistance. Interestingly, we also found that a small number of nonmotile cells were sufficient to block the swarming behavior of a large gliding-proficient population. This result suggests that an OME-derived signal could be amplified from a few nonmotile producers to act on many responder cells. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Targeted siRNA Screens Identify ER-to-Mitochondrial Calcium Exchange in Autophagy and Mitophagy Responses in RPE1 Cells

PubMed Central

MacVicar, Thomas D. B.; Mannack, Lilith V. J. C.; Lees, Robert M.; Lane, Jon D.

2015-01-01

Autophagy is an important stress response pathway responsible for the removal and recycling of damaged or redundant cytosolic constituents. Mitochondrial damage triggers selective mitochondrial autophagy (mitophagy), mediated by a variety of response factors including the Pink1/Parkin system. Using human retinal pigment epithelial cells stably expressing autophagy and mitophagy reporters, we have conducted parallel screens of regulators of endoplasmic reticulum (ER) and mitochondrial morphology and function contributing to starvation-induced autophagy and damage-induced mitophagy. These screens identified the ER chaperone and Ca2+ flux modulator, sigma non-opioid intracellular receptor 1 (SIGMAR1), as a regulator of autophagosome expansion during starvation. Screens also identified phosphatidyl ethanolamine methyl transferase (PEMT) and the IP3-receptors (IP3Rs) as mediators of Parkin-induced mitophagy. Further experiments suggested that IP3R-mediated transfer of Ca2+ from the ER lumen to the mitochondrial matrix via the mitochondrial Ca2+ uniporter (MCU) primes mitochondria for mitophagy. Importantly, recruitment of Parkin to damaged mitochondria did not require IP3R-mediated ER-to-mitochondrial Ca2+ transfer, but mitochondrial clustering downstream of Parkin recruitment was impaired, suggesting involvement of regulators of mitochondrial dynamics and/or transport. Our data suggest that Ca2+ flux between ER and mitochondria at presumed ER/mitochondrial contact sites is needed both for starvation-induced autophagy and for Parkin-mediated mitophagy, further highlighting the importance of inter-organellar communication for effective cellular homeostasis. PMID:26110381

Factors responsible for coverage and compliance in mass drug administration during the programme to eliminate lymphatic filariasis in the East Godavari District, South India.

PubMed

Babu, B V; Satyanarayana, K

2003-04-01

The paper attempts to report the factors responsible for the coverage and compliance of mass diethylcarbamazine citrate (DEC) administration, during the programme to eliminate lymphatic filariasis in the East Godavari District of Andhra Pradesh, India. The evaluation survey indicates that single dose DEC was received by 77% and taken by 64% of eligible people. Reasons for non-reception and non-consumption of the drug at household level were identified. The factors that influenced the coverage and compliance of treatment are broadly categorized as health services related, community related and drug related factors. The study identified some key factors to be followed for the success of the programme.

Genetic differences in transcript responses to low-dose ionizing radiation identify tissue functions associated with breast cancer susceptibility.

PubMed

Snijders, Antoine M; Marchetti, Francesco; Bhatnagar, Sandhya; Duru, Nadire; Han, Ju; Hu, Zhi; Mao, Jian-Hua; Gray, Joe W; Wyrobek, Andrew J

2012-01-01

High dose ionizing radiation (IR) is a well-known risk factor for breast cancer but the health effects after low-dose (LD, <10 cGy) exposures remain highly uncertain. We explored a systems approach that compared LD-induced chromosome damage and transcriptional responses in strains of mice with genetic differences in their sensitivity to radiation-induced mammary cancer (BALB/c and C57BL/6) for the purpose of identifying mechanisms of mammary cancer susceptibility. Unirradiated mammary and blood tissues of these strains differed significantly in baseline expressions of DNA repair, tumor suppressor, and stress response genes. LD exposures of 7.5 cGy (weekly for 4 weeks) did not induce detectable genomic instability in either strain. However, the mammary glands of the sensitive strain but not the resistant strain showed early transcriptional responses involving: (a) diminished immune response, (b) increased cellular stress, (c) altered TGFβ-signaling, and (d) inappropriate expression of developmental genes. One month after LD exposure, the two strains showed opposing responses in transcriptional signatures linked to proliferation, senescence, and microenvironment functions. We also discovered a pre-exposure expression signature in both blood and mammary tissues that is predictive for poor survival among human cancer patients (p = 0.0001), and a post-LD-exposure signature also predictive for poor patient survival (p<0.0001). There is concordant direction of expression in the LD-exposed sensitive mouse strain, in biomarkers of human DCIS and in biomarkers of human breast tumors. Our findings support the hypothesis that genetic mechanisms that determine susceptibility to LD radiation induced mammary cancer in mice are similar to the tissue mechanisms that determine poor-survival in breast cancer patients. We observed non-linearity of the LD responses providing molecular evidence against the LNT risk model and obtained new evidence that LD responses are strongly

Global Gene-Expression Analysis to Identify Differentially Expressed Genes Critical for the Heat Stress Response in Brassica rapa

PubMed Central

Dong, Xiangshu; Yi, Hankuil; Lee, Jeongyeo; Nou, Ill-Sup; Han, Ching-Tack; Hur, Yoonkang

2015-01-01

Genome-wide dissection of the heat stress response (HSR) is necessary to overcome problems in crop production caused by global warming. To identify HSR genes, we profiled gene expression in two Chinese cabbage inbred lines with different thermotolerances, Chiifu and Kenshin. Many genes exhibited >2-fold changes in expression upon exposure to 0.5– 4 h at 45°C (high temperature, HT): 5.2% (2,142 genes) in Chiifu and 3.7% (1,535 genes) in Kenshin. The most enriched GO (Gene Ontology) items included ‘response to heat’, ‘response to reactive oxygen species (ROS)’, ‘response to temperature stimulus’, ‘response to abiotic stimulus’, and ‘MAPKKK cascade’. In both lines, the genes most highly induced by HT encoded small heat shock proteins (Hsps) and heat shock factor (Hsf)-like proteins such as HsfB2A (Bra029292), whereas high-molecular weight Hsps were constitutively expressed. Other upstream HSR components were also up-regulated: ROS-scavenging genes like glutathione peroxidase 2 (BrGPX2, Bra022853), protein kinases, and phosphatases. Among heat stress (HS) marker genes in Arabidopsis, only exportin 1A (XPO1A) (Bra008580, Bra006382) can be applied to B. rapa for basal thermotolerance (BT) and short-term acquired thermotolerance (SAT) gene. CYP707A3 (Bra025083, Bra021965), which is involved in the dehydration response in Arabidopsis, was associated with membrane leakage in both lines following HS. Although many transcription factors (TF) genes, including DREB2A (Bra005852), were involved in HS tolerance in both lines, Bra024224 (MYB41) and Bra021735 (a bZIP/AIR1 [Anthocyanin-Impaired-Response-1]) were specific to Kenshin. Several candidate TFs involved in thermotolerance were confirmed as HSR genes by real-time PCR, and these assignments were further supported by promoter analysis. Although some of our findings are similar to those obtained using other plant species, clear differences in Brassica rapa reveal a distinct HSR in this species. Our data

Modelling categorical data to identify factors influencing concern for the natural environment in Iran.

PubMed

Parizanganeh, Abdolhossein; Lakhan, V Chris; Yazdani, Mahmoud; Ahmad, Sajid R

2011-10-01

Loglinear modelling techniques were used to identify the interactions and interrelationships underlying categorical environmental concern data collected from 9062 respondents in Iran. After fitting various loglinear models to the data, the most parsimonious model highlighted that a combination of interacting factors, namely educational attainment, age, gender, and residential location were responsible for influencing personal concern for the environment. Although high educational attainment had a close correspondence with high concern for the environment the loglinear results, when visualized with a geographical information system, demonstrated wide spatial variations in educational attainment and concern for the environment. Nearly two-thirds of the respondents were not highly educated, and were therefore not highly concerned for the environment. The finding that both rural and urban male and female respondents in the 15-24 years age category, with 10-12 years of education, had the strongest interaction with personal concern for the environment could be beneficial for policy planners to utilize education as the primary instrument to enhance environmental governance and prospects for sustainable development. Copyright © 2011 Elsevier Ltd. All rights reserved.

Transcriptomic analysis of rice aleurone cells identified a novel abscisic acid response element.

PubMed

Watanabe, Kenneth A; Homayouni, Arielle; Gu, Lingkun; Huang, Kuan-Ying; Ho, Tuan-Hua David; Shen, Qingxi J

2017-09-01

Seeds serve as a great model to study plant responses to drought stress, which is largely mediated by abscisic acid (ABA). The ABA responsive element (ABRE) is a key cis-regulatory element in ABA signalling. However, its consensus sequence (ACGTG(G/T)C) is present in the promoters of only about 40% of ABA-induced genes in rice aleurone cells, suggesting other ABREs may exist. To identify novel ABREs, RNA sequencing was performed on aleurone cells of rice seeds treated with 20 μM ABA. Gibbs sampling was used to identify enriched elements, and particle bombardment-mediated transient expression studies were performed to verify the function. Gene ontology analysis was performed to predict the roles of genes containing the novel ABREs. This study revealed 2443 ABA-inducible genes and a novel ABRE, designated as ABREN, which was experimentally verified to mediate ABA signalling in rice aleurone cells. Many of the ABREN-containing genes are predicted to be involved in stress responses and transcription. Analysis of other species suggests that the ABREN may be monocot specific. This study also revealed interesting expression patterns of genes involved in ABA metabolism and signalling. Collectively, this study advanced our understanding of diverse cis-regulatory sequences and the transcriptomes underlying ABA responses in rice aleurone cells. © 2017 John Wiley & Sons Ltd.

Identifying the readiness of patients in implementing telemedicine in northern Louisiana for an oncology practice.

PubMed

Gurupur, Varadraj; Shettian, Kruparaj; Xu, Peixin; Hines, Scott; Desselles, Mitzi; Dhawan, Manish; Wan, Thomas Th; Raffenaud, Amanda; Anderson, Lindsey

2017-09-01

This study identified the readiness factors that may create challenges in the use of telemedicine among patients in northern Louisiana with cancer. To identify these readiness factors, the team of investigators developed 19 survey questions that were provided to the patients or to their caregivers. The team collected responses from 147 respondents from rural and urban residential backgrounds. These responses were used to identify the individuals' readiness for utilising telemedicine through factor analysis, Cronbach's alpha reliability test, analysis of variance and ordinary least squares regression. The analysis results indicated that the favourable factor (positive readiness item) had a mean value of 3.47, whereas the unfavourable factor (negative readiness item) had a mean value of 2.76. Cronbach's alpha reliability test provided an alpha value of 0.79. Overall, our study indicated a positive attitude towards the use of telemedicine in northern Louisiana.

Linking Strengths: Identifying and Exploring Protective Factor Clusters in Academically Resilient Low-Socioeconomic Urban Students of Color

ERIC Educational Resources Information Center

Morales, Erik E.

2010-01-01

Based on data from qualitative interviews with 50 high-achieving low-socioeconomic students of color, two "clusters" of important and symbiotic protective factors are identified and explored. Each cluster consists of a series of interrelated protective factors identified by the participants as crucial to their statistically exceptional academic…

What factors influence ward nurses' recognition of and response to patient deterioration? An integrative review of the literature.

PubMed

Massey, Debbie; Chaboyer, Wendy; Anderson, Vinah

2017-01-01

In this integrative review, we aimed to: first, identify and summarize published studies relating to ward nurses' recognition of and response to patient deterioration; second, to critically evaluate studies that described or appraised the practice of ward nurses in recognizing and responding to patient deterioration; and third, identify gaps in the literature for further research. An integrative review. The Cumulative Index to Nursing and Allied Health Literature (CINAHL) Ovid Medline, Informit and Google Scholar databases were accessed for the years 1990-2014. Data were extracted and summarized in tables and then appraised using the Mixed Method Appraisal Tool. Data were grouped into two domains; recognizing and responding to deterioration and then thematic analysis was used to identify the emerging themes. Seventeen studies were reviewed and appraised. Recognizing patient deterioration was encapsulated in four themes: (1) assessing the patient; (2) knowing the patient; (3) education and (4) environmental factors. Responding to patient deterioration was encapsulated in three themes; (1) non-technical skills; (2) access to support and (3) negative emotional responses. Issues involved in timely recognition of and response to clinical deterioration remain complex, yet patient safety relies on nurses' timely assessments and actions.

Epigenetic priors for identifying active transcription factor binding sites.

PubMed

Cuellar-Partida, Gabriel; Buske, Fabian A; McLeay, Robert C; Whitington, Tom; Noble, William Stafford; Bailey, Timothy L

2012-01-01

Accurate knowledge of the genome-wide binding of transcription factors in a particular cell type or under a particular condition is necessary for understanding transcriptional regulation. Using epigenetic data such as histone modification and DNase I, accessibility data has been shown to improve motif-based in silico methods for predicting such binding, but this approach has not yet been fully explored. We describe a probabilistic method for combining one or more tracks of epigenetic data with a standard DNA sequence motif model to improve our ability to identify active transcription factor binding sites (TFBSs). We convert each data type into a position-specific probabilistic prior and combine these priors with a traditional probabilistic motif model to compute a log-posterior odds score. Our experiments, using histone modifications H3K4me1, H3K4me3, H3K9ac and H3K27ac, as well as DNase I sensitivity, show conclusively that the log-posterior odds score consistently outperforms a simple binary filter based on the same data. We also show that our approach performs competitively with a more complex method, CENTIPEDE, and suggest that the relative simplicity of the log-posterior odds scoring method makes it an appealing and very general method for identifying functional TFBSs on the basis of DNA and epigenetic evidence. FIMO, part of the MEME Suite software toolkit, now supports log-posterior odds scoring using position-specific priors for motif search. A web server and source code are available at http://meme.nbcr.net. Utilities for creating priors are at http://research.imb.uq.edu.au/t.bailey/SD/Cuellar2011. t.bailey@uq.edu.au Supplementary data are available at Bioinformatics online.

A critique of the use of indicator-species scores for identifying thresholds in species responses

USGS Publications Warehouse

Cuffney, Thomas F.; Qian, Song S.

2013-01-01

Identification of ecological thresholds is important both for theoretical and applied ecology. Recently, Baker and King (2010, King and Baker 2010) proposed a method, threshold indicator analysis (TITAN), to calculate species and community thresholds based on indicator species scores adapted from Dufrêne and Legendre (1997). We tested the ability of TITAN to detect thresholds using models with (broken-stick, disjointed broken-stick, dose-response, step-function, Gaussian) and without (linear) definitive thresholds. TITAN accurately and consistently detected thresholds in step-function models, but not in models characterized by abrupt changes in response slopes or response direction. Threshold detection in TITAN was very sensitive to the distribution of 0 values, which caused TITAN to identify thresholds associated with relatively small differences in the distribution of 0 values while ignoring thresholds associated with large changes in abundance. Threshold identification and tests of statistical significance were based on the same data permutations resulting in inflated estimates of statistical significance. Application of bootstrapping to the split-point problem that underlies TITAN led to underestimates of the confidence intervals of thresholds. Bias in the derivation of the z-scores used to identify TITAN thresholds and skewedness in the distribution of data along the gradient produced TITAN thresholds that were much more similar than the actual thresholds. This tendency may account for the synchronicity of thresholds reported in TITAN analyses. The thresholds identified by TITAN represented disparate characteristics of species responses that, when coupled with the inability of TITAN to identify thresholds accurately and consistently, does not support the aggregation of individual species thresholds into a community threshold.

Genome-Wide Transcriptome Analysis of Cotton (Gossypium hirsutum L.) Identifies Candidate Gene Signatures in Response to Aflatoxin Producing Fungus Aspergillus flavus.

PubMed

Bedre, Renesh; Rajasekaran, Kanniah; Mangu, Venkata Ramanarao; Sanchez Timm, Luis Eduardo; Bhatnagar, Deepak; Baisakh, Niranjan

2015-01-01

Aflatoxins are toxic and potent carcinogenic metabolites produced from the fungi Aspergillus flavus and A. parasiticus. Aflatoxins can contaminate cottonseed under conducive preharvest and postharvest conditions. United States federal regulations restrict the use of aflatoxin contaminated cottonseed at >20 ppb for animal feed. Several strategies have been proposed for controlling aflatoxin contamination, and much success has been achieved by the application of an atoxigenic strain of A. flavus in cotton, peanut and maize fields. Development of cultivars resistant to aflatoxin through overexpression of resistance associated genes and/or knocking down aflatoxin biosynthesis of A. flavus will be an effective strategy for controlling aflatoxin contamination in cotton. In this study, genome-wide transcriptome profiling was performed to identify differentially expressed genes in response to infection with both toxigenic and atoxigenic strains of A. flavus on cotton (Gossypium hirsutum L.) pericarp and seed. The genes involved in antifungal response, oxidative burst, transcription factors, defense signaling pathways and stress response were highly differentially expressed in pericarp and seed tissues in response to A. flavus infection. The cell-wall modifying genes and genes involved in the production of antimicrobial substances were more active in pericarp as compared to seed. The genes involved in auxin and cytokinin signaling were also induced. Most of the genes involved in defense response in cotton were highly induced in pericarp than in seed. The global gene expression analysis in response to fungal invasion in cotton will serve as a source for identifying biomarkers for breeding, potential candidate genes for transgenic manipulation, and will help in understanding complex plant-fungal interaction for future downstream research.

Use of a twin dataset to identify AMD-related visual patterns controlled by genetic factors

NASA Astrophysics Data System (ADS)

Quellec, Gwénolé; Abràmoff, Michael D.; Russell, Stephen R.

2010-03-01

The mapping of genotype to the phenotype of age-related macular degeneration (AMD) is expected to improve the diagnosis and treatment of the disease in a near future. In this study, we focused on the first step to discover this mapping: we identified visual patterns related to AMD which seem to be controlled by genetic factors, without explicitly relating them to the genes. For this purpose, we used a dataset of eye fundus photographs from 74 twin pairs, either monozygotic twins, who have the same genotype, or dizygotic twins, whose genes responsible for AMD are less likely to be identical. If we are able to differentiate monozygotic twins from dizygotic twins, based on a given visual pattern, then this pattern is likely to be controlled by genetic factors. The main visible consequence of AMD is the apparition of drusen between the retinal pigment epithelium and Bruch's membrane. We developed two automated drusen detectors based on the wavelet transform: a shape-based detector for hard drusen, and a texture- and color- based detector for soft drusen. Forty visual features were evaluated at the location of the automatically detected drusen. These features characterize the texture, the shape, the color, the spatial distribution, or the amount of drusen. A distance measure between twin pairs was defined for each visual feature; a smaller distance should be measured between monozygotic twins for visual features controlled by genetic factors. The predictions of several visual features (75.7% accuracy) are comparable or better than the predictions of human experts.

Identifying Items to Assess Methodological Quality in Physical Therapy Trials: A Factor Analysis

PubMed Central

Cummings, Greta G.; Fuentes, Jorge; Saltaji, Humam; Ha, Christine; Chisholm, Annabritt; Pasichnyk, Dion; Rogers, Todd

2014-01-01

Background Numerous tools and individual items have been proposed to assess the methodological quality of randomized controlled trials (RCTs). The frequency of use of these items varies according to health area, which suggests a lack of agreement regarding their relevance to trial quality or risk of bias. Objective The objectives of this study were: (1) to identify the underlying component structure of items and (2) to determine relevant items to evaluate the quality and risk of bias of trials in physical therapy by using an exploratory factor analysis (EFA). Design A methodological research design was used, and an EFA was performed. Methods Randomized controlled trials used for this study were randomly selected from searches of the Cochrane Database of Systematic Reviews. Two reviewers used 45 items gathered from 7 different quality tools to assess the methodological quality of the RCTs. An exploratory factor analysis was conducted using the principal axis factoring (PAF) method followed by varimax rotation. Results Principal axis factoring identified 34 items loaded on 9 common factors: (1) selection bias; (2) performance and detection bias; (3) eligibility, intervention details, and description of outcome measures; (4) psychometric properties of the main outcome; (5) contamination and adherence to treatment; (6) attrition bias; (7) data analysis; (8) sample size; and (9) control and placebo adequacy. Limitation Because of the exploratory nature of the results, a confirmatory factor analysis is needed to validate this model. Conclusions To the authors' knowledge, this is the first factor analysis to explore the underlying component items used to evaluate the methodological quality or risk of bias of RCTs in physical therapy. The items and factors represent a starting point for evaluating the methodological quality and risk of bias in physical therapy trials. Empirical evidence of the association among these items with treatment effects and a confirmatory factor

An inflammation-responsive transcription factor in the pathophysiology of osteoarthritis.

PubMed

Ray, Alpana; Ray, Bimal K

2008-01-01

A number of risk factors including biomechanical stress on the articular cartilage imposed by joint overloading due to obesity, repetitive damage of the joint tissues by injury of the menisci and ligaments, and abnormal joint alignment play a significant role in the onset of osteoarthritis (OA). Genetic predisposition can also lead to the formation of defective cartilage matrix because of abnormal gene expression in the cartilage-specific cells. Another important biochemical event in OA is the consequence of inflammation. It has been shown that synovial inflammation triggers the synthesis of biological stimuli such as cytokines and growth factors which subsequently reach the chondrocyte cells of the articular cartilage activating inflammatory events in the chondrocytes leading to cartilage destruction. In addition to cartilage degradation, hypertrophy of the subchondral bone and osteophyte formation at the joint margins also takes place in OA. Both processes involve abnormal expression of a number of genes including matrix metalloproteinases (MMPs) for cartilage degradation and those associated with bone formation during osteophyte development. To address how diverse groups of genes are activated in OA chondrocyte, we have studied their induction mechanism. We present evidence for abundant expression of an inflammation-responsive transcription factor, SAF-1, in moderate to severely damaged OA cartilage tissues. In contrast, cells in normal cartilage matrix contain very low level of SAF-1 protein. SAF-1 is identified as a major regulator of increased synthesis of MMP-1 and -9 and pro-angiogenic factor, vascular endothelial growth factor (VEGF). While VEGF by stimulating angiogenesis plays a key role in new bone formation in osteophyte, increase of MMP-1 and -9 is instrumental for cartilage erosion in the pathogenesis of OA. Increased expression in degenerated cartilage matrix and in the osteophytes indicate for a key regulatory role of SAF-1 in directing catabolic

ETHYLENE RESPONSE FACTOR 96 positively regulates Arabidopsis resistance to necrotrophic pathogens by direct binding to GCC elements of jasmonate - and ethylene-responsive defence genes.

PubMed

Catinot, Jérémy; Huang, Jing-Bo; Huang, Pin-Yao; Tseng, Min-Yuan; Chen, Ying-Lan; Gu, Shin-Yuan; Lo, Wan-Sheng; Wang, Long-Chi; Chen, Yet-Ran; Zimmerli, Laurent

2015-12-01

The ERF (ethylene responsive factor) family is composed of transcription factors (TFs) that are critical for appropriate Arabidopsis thaliana responses to biotic and abiotic stresses. Here we identified and characterized a member of the ERF TF group IX, namely ERF96, that when overexpressed enhances Arabidopsis resistance to necrotrophic pathogens such as the fungus Botrytis cinerea and the bacterium Pectobacterium carotovorum. ERF96 is jasmonate (JA) and ethylene (ET) responsive and ERF96 transcripts accumulation was abolished in JA-insensitive coi1-16 and in ET-insensitive ein2-1 mutants. Protoplast transactivation and electrophoresis mobility shift analyses revealed that ERF96 is an activator of transcription that binds to GCC elements. In addition, ERF96 mainly localized to the nucleus. Microarray analysis coupled to chromatin immunoprecipitation-PCR of Arabidopsis overexpressing ERF96 revealed that ERF96 enhances the expression of the JA/ET defence genes PDF1.2a, PR-3 and PR-4 as well as the TF ORA59 by direct binding to GCC elements present in their promoters. While ERF96-RNAi plants demonstrated wild-type resistance to necrotrophic pathogens, basal PDF1.2 expression levels were reduced in ERF96-silenced plants. This work revealed ERF96 as a key player of the ERF network that positively regulates the Arabidopsis resistance response to necrotrophic pathogens. © 2015 John Wiley & Sons Ltd.

Mga2 Transcription Factor Regulates an Oxygen-responsive Lipid Homeostasis Pathway in Fission Yeast*

PubMed Central

Burr, Risa; Stewart, Emerson V.; Shao, Wei; Zhao, Shan; Hannibal-Bach, Hans Kristian; Ejsing, Christer S.; Espenshade, Peter J.

2016-01-01

Eukaryotic lipid synthesis is oxygen-dependent with cholesterol synthesis requiring 11 oxygen molecules and fatty acid desaturation requiring 1 oxygen molecule per double bond. Accordingly, organisms evaluate oxygen availability to control lipid homeostasis. The sterol regulatory element-binding protein (SREBP) transcription factors regulate lipid homeostasis. In mammals, SREBP-2 controls cholesterol biosynthesis, whereas SREBP-1 controls triacylglycerol and glycerophospholipid biosynthesis. In the fission yeast Schizosaccharomyces pombe, the SREBP-2 homolog Sre1 regulates sterol homeostasis in response to changing sterol and oxygen levels. However, notably missing is an SREBP-1 analog that regulates triacylglycerol and glycerophospholipid homeostasis in response to low oxygen. Consistent with this, studies have shown that the Sre1 transcription factor regulates only a fraction of all genes up-regulated under low oxygen. To identify new regulators of low oxygen adaptation, we screened the S. pombe nonessential haploid deletion collection and identified 27 gene deletions sensitive to both low oxygen and cobalt chloride, a hypoxia mimetic. One of these genes, mga2, is a putative transcriptional activator. In the absence of mga2, fission yeast exhibited growth defects under both normoxia and low oxygen conditions. Mga2 transcriptional targets were enriched for lipid metabolism genes, and mga2Δ cells showed disrupted triacylglycerol and glycerophospholipid homeostasis, most notably with an increase in fatty acid saturation. Indeed, addition of exogenous oleic acid to mga2Δ cells rescued the observed growth defects. Together, these results establish Mga2 as a transcriptional regulator of triacylglycerol and glycerophospholipid homeostasis in S. pombe, analogous to mammalian SREBP-1. PMID:27053105

Use of clinical risk factors to identify postmenopausal women with vertebral fractures.

PubMed

Tobias, J H; Hutchinson, A P; Hunt, L P; McCloskey, E V; Stone, M D; Martin, J C; Thompson, P W; Palferman, T G; Bhalla, A K

2007-01-01

Previous studies have been unable to identify risk factors for prevalent vertebral fractures (VF), which are suitable for use in selection strategies intended to target high-risk sub-groups for diagnostic assessment. However, these studies generally consisted of large epidemiology surveys based on questionnaires and were only able to evaluate a limited number of risk factors. Here, we investigated whether a stronger relationship exists with prevalent VF when conventional risk factors are combined with additional information obtained from detailed one-to-one assessment. Women aged 65-75 registered at four geographically distinct GP practices were invited to participate (n=1,518), of whom 540 attended for assessment as follows: a questionnaire asking about risk factors for osteoporosis such as height loss compared to age 25 and history of non-vertebral fracture (NVF), the get-up-and-go test, Margolis back pain score, measurement of wall-tragus and rib-pelvis distances, and BMD as measured by the distal forearm BMD. A lateral thoraco-lumbar spine X-ray was obtained, which was subsequently scored for the presence of significant vertebral deformities. Of the 509 subjects who underwent spinal radiographs, 37 (7.3%) were found to have one or more VF. Following logistic regression analysis, the four most predictive clinical risk factors for prevalent VF were: height loss (P=0.006), past NVF (P=0.004), history of back pain (P=0.075) and age (P=0.05). BMD was also significantly associated with prevalent VF (P=0.002), but its inclusion did not affect associations with other variables. Factors elicited from detailed one-to-one assessment were not related to the risk of one or more prevalent VFs. The area under ROC curves derived from these regressions, which suggested that models for prevalent VF had modest predictive accuracy, were as follows: 0.68 (BMD), 0.74 (four clinical risk factors above) and 0.78 (clinical risk factors + BMD). Analyses were repeated in relation to the

Macrophage migration inhibitory factor polymorphisms do not predict therapeutic response to glucocorticoids or to tumour necrosis factor alpha-neutralising treatments in rheumatoid arthritis.

PubMed

Radstake, Timothy R D J; Fransen, Jaap; Toonen, Erik J M; Coenen, Marieke J H; Eijsbouts, Agnes E; Donn, Rachelle; van den Hoogen, Frank H J; van Riel, Piet L C M

2007-11-01

Macrophage migration inhibitory factor (MIF) is an inflammatory mediator associated with RA severity. In various diseases, MIF polymorphisms are associated with clinical response glucocorticoid (GC) treatment. It is unclear whether MIF polymorphisms determine GC response in rheumatoid arthritis (RA) and to other RA treatments. Therefore, the question of whether two functional variants in MIF are associated with the response to tumour necrosis factor (TNF)alpha-neutralising and GC treatments in RA was investigated. Data from two cohorts of an RA registry were used. For patients who started with TNFalpha-neutralising (infliximab) or GC treatment, courses with a duration of at least 3 months were included and response to TNFalpha blockers or GC was calculated according to the European League Against Rheumatism response criteria. MIF -173G-->C genotyping was achieved using an assay-on-demand allelic discrimination assay, and alleles of the CATT repeat element were identified using a fluorescently labelled PCR primer and capillary electrophoresis. Logistic-regression modelling was used for the statistical analysis. In total, 192 courses of oral prednisone or methylprednisolone injections in 98 patients with RA and 90 patients with RA who were on TNFalpha-neutralising treatments were documented. In all, 27% of the patients with RA were found to be heterozygous for seven CATT repeats (CATT(7)) and 31% were heterozygous for -173C. Respectively, 4% and 6% of the patients with RA were homozygous for the MIF CATT(7) repeat or the MIF -173C allele. Carrier status and homozygosity for CATT(7 )repeat and the MIF -173C allele were not associated with response to GC (odds ratios (ORs) close to 1) or to TNFalpha-neutralising treatment (ORs close to 2). The MIF-CATT(7) repeat and the MIF-173G-->C functional variant are not strongly associated with a decreased clinical response to TNFalpha-neutralising or GC treatment in RA.

Comparative Transcriptomics Highlights the Role of the Activator Protein 1 Transcription Factor in the Host Response to Ebolavirus

PubMed Central

Todd, Shawn; Boyd, Victoria; Tachedjian, Mary; Klein, Reuben; Shiell, Brian; Dearnley, Megan; McAuley, Alexander J.; Woon, Amanda P.; Purcell, Anthony W.; Marsh, Glenn A.; Baker, Michelle L.

2017-01-01

ABSTRACT Ebolavirus and Marburgvirus comprise two genera of negative-sense single-stranded RNA viruses that cause severe hemorrhagic fevers in humans. Despite considerable research efforts, the molecular events following Ebola virus (EBOV) infection are poorly understood. With the view of identifying host factors that underpin EBOV pathogenesis, we compared the transcriptomes of EBOV-infected human, pig, and bat kidney cells using a transcriptome sequencing (RNA-seq) approach. Despite a significant difference in viral transcription/replication between the cell lines, all cells responded to EBOV infection through a robust induction of extracellular growth factors. Furthermore, a significant upregulation of activator protein 1 (AP1) transcription factor complex members FOS and JUN was observed in permissive cell lines. Functional studies focusing on human cells showed that EBOV infection induces protein expression, phosphorylation, and nuclear accumulation of JUN and, to a lesser degree, FOS. Using a luciferase-based reporter, we show that EBOV infection induces AP1 transactivation activity within human cells at 48 and 72 h postinfection. Finally, we show that JUN knockdown decreases the expression of EBOV-induced host gene expression. Taken together, our study highlights the role of AP1 in promoting the host gene expression profile that defines EBOV pathogenesis. IMPORTANCE Many questions remain about the molecular events that underpin filovirus pathophysiology. The rational design of new intervention strategies, such as postexposure therapeutics, will be significantly enhanced through an in-depth understanding of these molecular events. We believe that new insights into the molecular pathogenesis of EBOV may be possible by examining the transcriptomic response of taxonomically diverse cell lines (derived from human, pig, and bat). We first identified the responsive pathways using an RNA-seq-based transcriptomics approach. Further functional and computational

Identifying Trajectories of Adolescents' Depressive Phenomena: An Examination of Early Risk Factors

ERIC Educational Resources Information Center

Mazza, James J.; Fleming, Charles B.; Abbott, Robert D.; Haggerty, Kevin P.; Catalano, Richard F.

2010-01-01

Few studies have examined risk factors of childhood and early adolescent depressive symptomatology trajectories. This study examined self-report depressive symptomatology across a 6-year time period from 2nd to 8th grade to identify latent groups of individuals with similar patterns of depressive phenomena in a sample of 951 children (440 girls,…

A review of factors influencing the stress response in Australian marsupials

PubMed Central

Hing, Stephanie; Narayan, Edward; Thompson, R. C. Andrew; Godfrey, Stephanie

2014-01-01

Many Australian marsupials are threatened species. In order to manage in situ and ex situ populations effectively, it is important to understand how marsupials respond to threats. Stress physiology (the study of the response of animals to challenging stimuli), a key approach in conservation physiology, can be used to characterize the physiological response of wildlife to threats. We reviewed the literature on the measurement of glucocorticoids (GCs), endocrine indicators of stress, in order to understand the stress response to conservation-relevant stressors in Australian marsupials and identified 29 studies. These studies employed a range of methods to measure GCs, with faecal glucocorticoid metabolite enzyme immunoassay being the most common method. The main stressors considered in studies of marsupials were capture and handling. To date, the benefits of stress physiology have yet to be harnessed fully in marsupial conservation. Despite a theoretical base dating back to the 1960s, GCs have only been used to understand how 21 of the 142 extant species of Australian marsupial respond to stressors. These studies include merely six of the 60 marsupial species of conservation concern (IUCN Near Threatened to Critically Endangered). Furthermore, the fitness consequences of stress for Australian marsupials are rarely examined. Individual and species differences in the physiological stress response also require further investigation, because significant species-specific variations in GC levels in response to stressors can shed light on why some individuals or species are more vulnerable to stress factors while others appear more resilient. This review summarizes trends, knowledge gaps and future research directions for stress physiology research in Australian marsupial conservation. PMID:27293648

Response to Growth Hormone Treatment in a Patient with Insulin-Like Growth Factor 1 Receptor Deletion

PubMed Central

Mahmoud, Ranim; Naidu, Ajanta; Risheg, Hiba; Kimonis, Virginia

2017-01-01

We report a six-year-old boy who presented with short stature, microcephaly, dysmorphic features, and developmental delay and who was identified with a terminal deletion of 15q26.2q26.3 containing the insulin-like growth factor receptor (IGF1R) gene in addition to a terminal duplication of the 4q35.1q35.2 region. We compare our case with other reports of deletions and mutations affecting the IGF1R gene associated with pre-and postnatal growth restriction. We report the dramatic response to growth hormone therapy in this patient which highlights the importance of identifying patients with IGF1R deletion and treating them early. PMID:28720553

Response to Growth Hormone Treatment in a Patient with Insulin-Like Growth Factor 1 Receptor Deletion.

PubMed

Mahmoud, Ranim; Naidu, Ajanta; Risheg, Hiba; Kimonis, Virginia

2017-12-15

We report a six-year-old boy who presented with short stature, microcephaly, dysmorphic features, and developmental delay and who was identified with a terminal deletion of 15q26.2q26.3 containing the insulin-like growth factor receptor (IGF1R) gene in addition to a terminal duplication of the 4q35.1q35.2 region. We compare our case with other reports of deletions and mutations affecting the IGF1R gene associated with pre-and postnatal growth restriction. We report the dramatic response to growth hormone therapy in this patient which highlights the importance of identifying patients with IGF1R deletion and treating them early.

Integration of growth factor signals at the c-fos serum response element.

PubMed

Price, M A; Hill, C; Treisman, R

1996-04-29

A transcription factor ternary complex composed of serum response factor (SRF) and a second factor, ternary complex factor (TCF), mediates the response of the c-fos Serum Response Element to growth factors and mitogens. In NIH3T3 fibroblasts, TCF binding is required for transcriptional activation by the SRE in response to activation of the Ras-Raf-ERK pathway. We compared the properties of three members of the TCF family, Elk-1, SAP-1 and SAP-2 (ERP/NET). Although all the proteins contain sequences required for ternary complex formation with SRF, only Elk-1 and SAP-1 appear to interact with the c-fos SRE efficiently in vivo. Each TCF contains a C-terminal activation domain capable of transcriptional activation in response to activation of the Ras-Raf-ERK pathway, and this is dependent on the integrity of S/T-P motifs conserved between all the TCF family members. In contrast, activation of the SRE by whole serum and the mitogenic phospholipid LPA requires SRF binding alone. Constitutively activated members of the Rho subfamily of Ras-like GTPases are also capable of inducing activation of the SRE in the absence of TCF; unlike activated Ras itself, these proteins do not activate the TCFs in NIH3T3 cells. At the SRE, SRF- and TCF-linked signalling pathways act synergistically to potentiate transcription.

Plant MYB Transcription Factors: Their Role in Drought Response Mechanisms

PubMed Central

Baldoni, Elena; Genga, Annamaria; Cominelli, Eleonora

2015-01-01

Water scarcity is one of the major causes of poor plant performance and limited crop yields worldwide and it is the single most common cause of severe food shortage in developing countries. Several molecular networks involved in stress perception, signal transduction and stress responses in plants have been elucidated so far. Transcription factors are major players in water stress signaling. In recent years, different MYB transcription factors, mainly in Arabidopsis thaliana (L.) Heynh. but also in some crops, have been characterized for their involvement in drought response. For some of them there is evidence supporting a specific role in response to water stress, such as the regulation of stomatal movement, the control of suberin and cuticular waxes synthesis and the regulation of flower development. Moreover, some of these genes have also been characterized for their involvement in other abiotic or biotic stresses, an important feature considering that in nature, plants are often simultaneously subjected to multiple rather than single environmental perturbations. This review summarizes recent studies highlighting the role of the MYB family of transcription factors in the adaptive responses to drought stress. The practical application value of MYBs in crop improvement, such as stress tolerance engineering, is also discussed. PMID:26184177

Plant MYB Transcription Factors: Their Role in Drought Response Mechanisms.

PubMed

Baldoni, Elena; Genga, Annamaria; Cominelli, Eleonora

2015-07-13

Water scarcity is one of the major causes of poor plant performance and limited crop yields worldwide and it is the single most common cause of severe food shortage in developing countries. Several molecular networks involved in stress perception, signal transduction and stress responses in plants have been elucidated so far. Transcription factors are major players in water stress signaling. In recent years, different MYB transcription factors, mainly in Arabidopsis thaliana (L.) Heynh. but also in some crops, have been characterized for their involvement in drought response. For some of them there is evidence supporting a specific role in response to water stress, such as the regulation of stomatal movement, the control of suberin and cuticular waxes synthesis and the regulation of flower development. Moreover, some of these genes have also been characterized for their involvement in other abiotic or biotic stresses, an important feature considering that in nature, plants are often simultaneously subjected to multiple rather than single environmental perturbations. This review summarizes recent studies highlighting the role of the MYB family of transcription factors in the adaptive responses to drought stress. The practical application value of MYBs in crop improvement, such as stress tolerance engineering, is also discussed.

USE OF THE RIBONUCLEASE PROTECTION ASSAY FOR IDENTIFYING CHEMICALS WHICH ELLICIT HYPERSENSITIVITY RESPONSES

EPA Science Inventory

Use of the Ribonuclease Protection Assay (RPA) for Identifying Chemicals that Elicit Hypersensitivity Responses. L.M. Plitnick, 1, D.M. Sailstad, 2, and R.J. Smialowicz, 2 1UNC, Curriculum in Toxicology, Chapel Hill, NC and 2USEPA, NHEERL, RTP, NC.

The incidence of aller...

An independent component analysis confounding factor correction framework for identifying broad impact expression quantitative trait loci

PubMed Central

Ju, Jin Hyun; Crystal, Ronald G.

2017-01-01

Genome-wide expression Quantitative Trait Loci (eQTL) studies in humans have provided numerous insights into the genetics of both gene expression and complex diseases. While the majority of eQTL identified in genome-wide analyses impact a single gene, eQTL that impact many genes are particularly valuable for network modeling and disease analysis. To enable the identification of such broad impact eQTL, we introduce CONFETI: Confounding Factor Estimation Through Independent component analysis. CONFETI is designed to address two conflicting issues when searching for broad impact eQTL: the need to account for non-genetic confounding factors that can lower the power of the analysis or produce broad impact eQTL false positives, and the tendency of methods that account for confounding factors to model broad impact eQTL as non-genetic variation. The key advance of the CONFETI framework is the use of Independent Component Analysis (ICA) to identify variation likely caused by broad impact eQTL when constructing the sample covariance matrix used for the random effect in a mixed model. We show that CONFETI has better performance than other mixed model confounding factor methods when considering broad impact eQTL recovery from synthetic data. We also used the CONFETI framework and these same confounding factor methods to identify eQTL that replicate between matched twin pair datasets in the Multiple Tissue Human Expression Resource (MuTHER), the Depression Genes Networks study (DGN), the Netherlands Study of Depression and Anxiety (NESDA), and multiple tissue types in the Genotype-Tissue Expression (GTEx) consortium. These analyses identified both cis-eQTL and trans-eQTL impacting individual genes, and CONFETI had better or comparable performance to other mixed model confounding factor analysis methods when identifying such eQTL. In these analyses, we were able to identify and replicate a few broad impact eQTL although the overall number was small even when applying CONFETI. In

An independent component analysis confounding factor correction framework for identifying broad impact expression quantitative trait loci.

PubMed

Ju, Jin Hyun; Shenoy, Sushila A; Crystal, Ronald G; Mezey, Jason G

2017-05-01

Genome-wide expression Quantitative Trait Loci (eQTL) studies in humans have provided numerous insights into the genetics of both gene expression and complex diseases. While the majority of eQTL identified in genome-wide analyses impact a single gene, eQTL that impact many genes are particularly valuable for network modeling and disease analysis. To enable the identification of such broad impact eQTL, we introduce CONFETI: Confounding Factor Estimation Through Independent component analysis. CONFETI is designed to address two conflicting issues when searching for broad impact eQTL: the need to account for non-genetic confounding factors that can lower the power of the analysis or produce broad impact eQTL false positives, and the tendency of methods that account for confounding factors to model broad impact eQTL as non-genetic variation. The key advance of the CONFETI framework is the use of Independent Component Analysis (ICA) to identify variation likely caused by broad impact eQTL when constructing the sample covariance matrix used for the random effect in a mixed model. We show that CONFETI has better performance than other mixed model confounding factor methods when considering broad impact eQTL recovery from synthetic data. We also used the CONFETI framework and these same confounding factor methods to identify eQTL that replicate between matched twin pair datasets in the Multiple Tissue Human Expression Resource (MuTHER), the Depression Genes Networks study (DGN), the Netherlands Study of Depression and Anxiety (NESDA), and multiple tissue types in the Genotype-Tissue Expression (GTEx) consortium. These analyses identified both cis-eQTL and trans-eQTL impacting individual genes, and CONFETI had better or comparable performance to other mixed model confounding factor analysis methods when identifying such eQTL. In these analyses, we were able to identify and replicate a few broad impact eQTL although the overall number was small even when applying CONFETI. In

Casein kinase 2 and the cell response to growth factors.

PubMed

Filhol-Cochet, O; Loue-Mackenbach, P; Cochet, C; Chambaz, E M

1994-01-01

Different approaches have been followed with the aim of delineating a possible role of casein kinase 2 (CK2) in the mitogenic signalling in response to cell growth factors. (a) Immunocytochemical detection of CK2 showed that while the kinase is evenly distributed throughout cycle arrested cells, it becomes preferentially associated with the nuclear compartment in activity growing cells; (b) CK2 biosynthesis is activated as an early response of quiescent cells to growth factors. The newly synthesized CK2 steadily accumulates as the cells progress through the G1 phase. This growth factor-induced CK2 biosynthesis involves in parallel the two alpha and beta subunits of the kinase, with no detectable preferential subcellular localization of the newly synthesized enzyme; and (c) In addition to substrate phosphorylation, CK2 may form molecular complexes with cell components of functional significance. Such is the case with the protein p53, a major negative regulator of the cell cycle. CK2 forms a high affinity association (Kd 70 nM) with p53, through its beta subunit. The complex dissociates in the presence of adenosine triphosphate (ATP). These observations suggest that CK2 and p53 may play a coordinated regulatory role in the cell response to growth factors.

Homeodomain Transcription Factor Msx-2 Regulates Uterine Progenitor Cell Response to Diethylstilbestrol

PubMed Central

Yin, Yan; Lin, Congxing; Zhang, Ivy; Fisher, Alexander V; Dhandha, Maulik; Ma, Liang

2015-01-01

The fate of mouse uterine epithelial progenitor cells is determined between postnatal days 5 to 7. Around this critical time window, exposure to an endocrine disruptor, diethylstilbestrol (DES), can profoundly alter uterine cytodifferentiation. We have shown previously that a homeo domain transcription factor MSX-2 plays an important role in DES-responsiveness in the female reproductive tract (FRT). Mutant FRTs exhibited a much more severe phenotype when treated with DES, accompanied by gene expression changes that are dependent on Msx2. To better understand the role that MSX-2 plays in uterine response to DES, we performed global gene expression profiling experiment in mice lacking Msx2 By comparing this result to our previously published microarray data performed on wild-type mice, we extracted common and differentially regulated genes in the two genotypes. In so doing, we identified potential downstream targets of MSX-2, as well as genes whose regulation by DES is modulated through MSX-2. Discovery of these genes will lead to a better understanding of how DES, and possibly other endocrine disruptors, affects reproductive organ development. PMID:26457333

Homeodomain Transcription Factor Msx-2 Regulates Uterine Progenitor Cell Response to Diethylstilbestrol.

PubMed

Yin, Yan; Lin, Congxing; Zhang, Ivy; Fisher, Alexander V; Dhandha, Maulik; Ma, Liang

The fate of mouse uterine epithelial progenitor cells is determined between postnatal days 5 to 7. Around this critical time window, exposure to an endocrine disruptor, diethylstilbestrol (DES), can profoundly alter uterine cytodifferentiation. We have shown previously that a homeo domain transcription factor MSX-2 plays an important role in DES-responsiveness in the female reproductive tract (FRT). Mutant FRTs exhibited a much more severe phenotype when treated with DES, accompanied by gene expression changes that are dependent on Msx2 . To better understand the role that MSX-2 plays in uterine response to DES, we performed global gene expression profiling experiment in mice lacking Msx2 By comparing this result to our previously published microarray data performed on wild-type mice, we extracted common and differentially regulated genes in the two genotypes. In so doing, we identified potential downstream targets of MSX-2, as well as genes whose regulation by DES is modulated through MSX-2. Discovery of these genes will lead to a better understanding of how DES, and possibly other endocrine disruptors, affects reproductive organ development.

Development of novel metabolite-responsive transcription factors via transposon-mediated protein fusion.

PubMed

Younger, Andrew K D; Su, Peter Y; Shepard, Andrea J; Udani, Shreya V; Cybulski, Thaddeus R; Tyo, Keith E J; Leonard, Joshua N

2018-02-01

Naturally evolved metabolite-responsive biosensors enable applications in metabolic engineering, ranging from screening large genetic libraries to dynamically regulating biosynthetic pathways. However, there are many metabolites for which a natural biosensor does not exist. To address this need, we developed a general method for converting metabolite-binding proteins into metabolite-responsive transcription factors-Biosensor Engineering by Random Domain Insertion (BERDI). This approach takes advantage of an in vitro transposon insertion reaction to generate all possible insertions of a DNA-binding domain into a metabolite-binding protein, followed by fluorescence activated cell sorting to isolate functional biosensors. To develop and evaluate the BERDI method, we generated a library of candidate biosensors in which a zinc finger DNA-binding domain was inserted into maltose binding protein, which served as a model well-studied metabolite-binding protein. Library diversity was characterized by several methods, a selection scheme was deployed, and ultimately several distinct and functional maltose-responsive transcriptional biosensors were identified. We hypothesize that the BERDI method comprises a generalizable strategy that may ultimately be applied to convert a wide range of metabolite-binding proteins into novel biosensors for applications in metabolic engineering and synthetic biology. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Capsicum annuum WRKY transcription factor d (CaWRKYd) regulates hypersensitive response and defense response upon Tobacco mosaic virus infection.

PubMed

Huh, Sung Un; Choi, La Mee; Lee, Gil-Je; Kim, Young Jin; Paek, Kyung-Hee

2012-12-01

WRKY transcription factors regulate biotic, abiotic, and developmental processes. In terms of plant defense, WRKY factors have important roles as positive and negative regulators via transcriptional regulation or protein-protein interaction. Here, we report the characterization of the gene encoding Capsicum annuum WRKY transcription factor d (CaWRKYd) isolated from microarray analysis in the Tobacco mosaic virus (TMV)-P(0)-inoculated hot pepper plants. CaWRKYd belongs to the WRKY IIa group, a very small clade in the WRKY subfamily, and WRKY IIa group has positive/negative regulatory roles in Arabidopsis and rice. CaWRKYd transcripts were induced by various plant defense-related hormone treatments and TMV-P(0) inoculation. Silencing of CaWRKYd affected TMV-P(0)-mediated hypersensitive response (HR) cell death and accumulation of TMV-P(0) coat protein in local and systemic leaves. Furthermore, expression of some pathogenesis-related (PR) genes and HR-related genes was reduced in the CaWRKYd-silenced plants compared with TRV2 vector control plants upon TMV-P(0) inoculation. CaWRKYd was confirmed to bind to the W-box. Thus CaWRKYd is a newly identified Capsicum annuum WRKY transcription factor that appears to be involved in TMV-P(0)-mediated HR cell death by regulating downstream gene expression. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Predictive factors in the evaluation of treatment response to neoadjuvant chemoradiotherapy in patients with advanced esophageal squamous cell cancer

PubMed Central

Wong, Claudia

2017-01-01

Neoadjuvant therapy before esophagectomy is evidence-based, and is a standard-of-care for locally advanced and operable esophageal cancer. However response to such treatment varies in individual patients, from no clinical response to pathological complete response. It has been consistently shown that a good pathological responses is of prognostic value, but perhaps in the expense of those who do not. It is important to identify suitable predictive factors for response, so that patients are not exposed to potentially harmful chemotherapy and/or radiotherapy without benefits. Alternative management strategies can be devised. Various clinical, radiological, serological and potential molecular markers have been studied. None has been shown to be sufficiently reliable to be used in daily practice. Certainly more understanding of the molecular basis for response to chemotherapy/radiotherapy is needed, so that patient treatment can be tailored and individualized. PMID:28815073

Emotional Responses to Suicidal Patients: Factor Structure, Construct, and Predictive Validity of the Therapist Response Questionnaire-Suicide Form.

PubMed

Barzilay, Shira; Yaseen, Zimri S; Hawes, Mariah; Gorman, Bernard; Altman, Rachel; Foster, Adriana; Apter, Alan; Rosenfield, Paul; Galynker, Igor

2018-01-01

Mental health professionals have a pivotal role in suicide prevention. However, they also often have intense emotional responses, or countertransference, during encounters with suicidal patients. Previous studies of the Therapist Response Questionnaire-Suicide Form (TRQ-SF), a brief novel measure aimed at probing a distinct set of suicide-related emotional responses to patients found it to be predictive of near-term suicidal behavior among high suicide-risk inpatients. The purpose of this study was to validate the TRQ-SF in a general outpatient clinic setting. Adult psychiatric outpatients ( N  = 346) and their treating mental health professionals ( N  = 48) completed self-report assessments following their first clinic meeting. Clinician measures included the TRQ-SF, general emotional states and traits, therapeutic alliance, and assessment of patient suicide risk. Patient suicidal outcomes and symptom severity were assessed at intake and one-month follow-up. Following confirmatory factor analysis of the TRQ-SF, factor scores were examined for relationships with clinician and patient measures and suicidal outcomes. Factor analysis of the TRQ-SF confirmed three dimensions: (1) affiliation, (2) distress, and (3) hope. The three factors also loaded onto a single general factor of negative emotional response toward the patient that demonstrated good internal reliability. The TRQ-SF scores were associated with measures of clinician state anger and anxiety and therapeutic alliance, independently of clinician personality traits after controlling for the state- and patient-specific measures. The total score and three subscales were associated in both concurrent and predictive ways with patient suicidal outcomes, depression severity, and clinicians' judgment of patient suicide risk, but not with global symptom severity, thus indicating specifically suicide-related responses. The TRQ-SF is a brief and reliable measure with a 3-factor structure. It demonstrates

Considering baseline factors and early response rates to optimize therapy for chronic myeloid leukemia in chronic phase.

PubMed

Akard, Luke P; Bixby, Dale

2016-05-01

Multiple BCR-ABL tyrosine kinase inhibitors (TKIs) are available for the treatment of chronic myeloid leukemia in chronic phase (CML-CP), and several baseline and on-treatment predictive factors have been identified that can be used to help guide TKI selection for individual patients. In particular, early molecular response (EMR; BCR-ABL ≤10% on the International Scale at 3 months) has become an accepted benchmark for evaluating whether patients with CML-CP are responding optimally to frontline TKI therapy. Failure to achieve EMR is considered an inadequate initial response according to the National Comprehensive Cancer Network guidelines and a warning response according to the European LeukemiaNet recommendations. Here we review data supporting the importance of achieving EMR for improving patients' long-term outcomes and discuss key considerations for selecting a frontline TKI in light of these data. Because a higher proportion of patients achieve EMR with second-generation TKIs such as nilotinib and dasatinib than with imatinib, these TKIs may be preferable for many patients, particularly those with known negative prognostic factors at baseline. We also discuss other considerations for frontline TKI choice, including toxicities, cost-effectiveness, and the emerging goals of deep molecular response and treatment-free remission.

Egr-1 and serum response factor are involved in growth factors- and serum-mediated induction of E2-EPF UCP expression that regulates the VHL-HIF pathway.

PubMed

Lim, Jung Hwa; Jung, Cho-Rok; Lee, Chan-Hee; Im, Dong-Soo

2008-11-01

E2-EPF ubiquitin carrier protein (UCP) has been shown to be highly expressed in common human cancers and target von Hippel-Lindau (VHL) for proteosomal degradation in cells, thereby stabilizing hypoxia-inducible factor (HIF)-1alpha. Here, we investigated cellular factors that regulate the expression of UCP gene. Promoter deletion assay identified binding sites for early growth response-1 (Egr-1) and serum response factor (SRF) in the UCP promoter. Hepatocyte or epidermal growth factor (EGF), or phorbol 12-myristate 13-acetate induced UCP expression following early induction of Egr-1 expression in HeLa cells. Serum increased mRNA and protein levels of SRF and UCP in the cell. By electrophoretic mobility shift and chromatin immunoprecipitation assays, sequence-specific DNA-binding of Egr-1 and SRF to the UCP promoter was detected in nuclear extracts from HeLa cells treated with EGF and serum, respectively. Overexpression of Egr-1 or SRF increased UCP expression. RNA interference-mediated depletion of endogenous Egr-1 or SRF impaired EGF- or serum-mediated induction of UCP expression, which was required for cancer cell proliferation. Systemic delivery of EGF into mice also increased UCP expression following early induction of Egr-1 expression in mouse liver. The induced UCP expression by the growth factors or serum increased HIF-1alpha protein level under non-hypoxic conditions, suggesting that the Egr-1/SRF-UCP-VHL pathway is in part responsible for the increased HIF-1alpha protein level in vitro and in vivo. Thus, growth factors and serum induce expression of Egr-1 and SRF, respectively, which in turn induces UCP expression that positively regulates cancer cell growth.

IscR Regulates Synthesis of Colonization Factor Antigen I Fimbriae in Response to Iron Starvation in Enterotoxigenic Escherichia coli

PubMed Central

Arnaud-Barbe, Nadège; Poncet, David; Reverchon, Sylvie; Wawrzyniak, Julien; Nasser, William

2015-01-01

ABSTRACT Iron availability functions as an environmental cue for enteropathogenic bacteria, signaling arrival within the human host. As enterotoxigenic Escherichia coli (ETEC) is a major cause of human diarrhea, the effect of iron on ETEC virulence factors was evaluated here. ETEC pathogenicity is directly linked to production of fimbrial colonization factors and secretion of heat-labile enterotoxin (LT) and/or heat-stable enterotoxin (ST). Efficient colonization of the small intestine further requires at least the flagellin binding adhesin EtpA. Under iron starvation, production of the CFA/I fimbriae was increased in the ETEC H10407 prototype strain. In contrast, LT secretion was inhibited. Furthermore, under iron starvation, gene expression of the cfa (CFA/I) and etp (EtpBAC) operons was induced, whereas transcription of toxin genes was either unchanged or repressed. Transcriptional reporter fusion experiments focusing on the cfa operon further showed that iron starvation stimulated cfaA promoter activity in ETEC, indicating that the impact of iron on CFA/I production was mediated by transcriptional regulation. Evaluation of cfaA promoter activity in heterologous E. coli single mutant knockout strains identified IscR as the regulator responsible for inducing cfa fimbrial gene expression in response to iron starvation, and this was confirmed in an ETEC ΔiscR strain. The global iron response regulator, Fur, was not implicated. IscR binding sites were identified in silico within the cfaA promoter and fixation confirmed by DNase I footprinting, indicating that IscR directly binds the promoter region to induce CFA/I. IMPORTANCE Pathogenic enterobacteria modulate expression of virulence genes in response to iron availability. Although the Fur transcription factor represents the global regulator of iron homeostasis in Escherichia coli, we show that several ETEC virulence factors are modulated by iron, with expression of the major fimbriae under the control of the iron

Identifying the factors underlying discontinuation of triptans.

PubMed

Wells, Rebecca E; Markowitz, Shira Y; Baron, Eric P; Hentz, Joseph G; Kalidas, Kavita; Mathew, Paul G; Halker, Rashmi; Dodick, David W; Schwedt, Todd J

2014-02-01

To identify factors associated with triptan discontinuation among migraine patients. It is unclear why many migraine patients who are prescribed triptans discontinue this treatment. This study investigated correlates of triptan discontinuation with a focus on potentially modifiable factors to improve compliance. This multicenter cross-sectional survey (n = 276) was performed at US tertiary care headache clinics. Headache fellows who were members of the American Headache Society Headache Fellows Research Consortium recruited episodic and chronic migraine patients who were current triptan users (use within prior 3 months and for ≥1 year) or past triptan users (no use within 6 months; prior use within 2 years). Univariate analyses were first completed to compare current triptan users to past users for: migraine characteristics, other migraine treatments, triptan education, triptan efficacy, triptan side effects, type of prescribing provider, Migraine Disability Assessment (MIDAS) scores and Beck Depression Inventory (BDI) scores. Then, a multivariable logistic regression model was selected from all possible combinations of predictor variables to determine the factors that best correlated with triptan discontinuation. Compared with those still using triptans (n = 207), those who had discontinued use (n = 69) had higher rates of medication overuse (30 vs. 18%, P = .04) and were more likely to have ever used opioids for migraine treatment (57 vs. 38%, P = .006) as well as higher MIDAS (mean 63 vs. 37, P = .001) and BDI scores (mean 10.4 vs. 7.4, P = .009). Compared with discontinued users, current triptan users were more likely to have had their triptan prescribed by a specialist (neurologist, headache specialist, or pain specialist) (74 vs. 54%, P = .002) and were more likely to report headache resolution (53 vs. 14%, P < .001) or a reduction in pain intensity (71 vs. 28%, P < .001) most of the time from their triptan. On a 1

Nurse-Administered, Gut-Directed Hypnotherapy in IBS: Efficacy and Factors Predicting a Positive Response.

PubMed

Lövdahl, Jenny; Ringström, Gisela; Agerforz, Pia; Törnblom, Hans; Simrén, Magnus

2015-07-01

Hypnotherapy is an effective treatment in irritable bowel syndrome (IBS). It is often delivered by a psychotherapist and is costly and time consuming. Nurse-administered hypnotherapy could increase availability and reduce costs. In this study the authors evaluate the effectiveness of nurse-administered, gut-directed hypnotherapy and identify factors predicting treatment outcome. Eighty-five patients were included in the study. Participants received hypnotherapy by a nurse once/week for 12 weeks. Patients reported marked improvement in gastrointestinal (GI) and extra-colonic symptoms after treatment, as well as a reduction in GI-specific anxiety, general anxiety, and depression. Fifty-eight percent were responders after the 12 weeks treatment period, and of these 82% had a favorable clinical response already at week 6. Women were more likely than men to respond favorably to the treatment. Nurse-administered hypnotherapy is an effective treatment for IBS. Being female and reporting a favorable response to treatment by week 6 predicted a positive treatment response at the end of the 12 weeks treatment period.

Quantitative Proteomic Approach Identifies Vpr Binding Protein as Novel Host Factor Supporting Influenza A Virus Infections in Human Cells.

PubMed

Sadewasser, Anne; Paki, Katharina; Eichelbaum, Katrin; Bogdanow, Boris; Saenger, Sandra; Budt, Matthias; Lesch, Markus; Hinz, Klaus-Peter; Herrmann, Andreas; Meyer, Thomas F; Karlas, Alexander; Selbach, Matthias; Wolff, Thorsten

2017-05-01

Influenza A virus (IAV) infections are a major cause for respiratory disease in humans, which affects all age groups and contributes substantially to global morbidity and mortality. IAV have a large natural host reservoir in avian species. However, many avian IAV strains lack adaptation to other hosts and hardly propagate in humans. While seasonal or pandemic IAV strains replicate efficiently in permissive human cells, many avian IAV cause abortive nonproductive infections in these hosts despite successful cell entry. However, the precise reasons for these differential outcomes are poorly defined. We hypothesized that the distinct course of an IAV infection with a given virus strain is determined by the differential interplay between specific host and viral factors. By using Spike-in SILAC mass spectrometry-based quantitative proteomics we characterized sets of cellular factors whose abundance is specifically up- or downregulated in the course of permissive versus nonpermissive IAV infection, respectively. This approach allowed for the definition and quantitative comparison of about 3500 proteins in human lung epithelial cells in response to seasonal or low-pathogenic avian H3N2 IAV. Many identified proteins were similarly regulated by both virus strains, but also 16 candidates with distinct changes in permissive versus nonpermissive infection were found. RNAi-mediated knockdown of these differentially regulated host factors identified Vpr binding protein (VprBP) as proviral host factor because its downregulation inhibited efficient propagation of seasonal IAV whereas overexpression increased viral replication of both seasonal and avian IAV. These results not only show that there are similar differences in the overall changes during permissive and nonpermissive influenza virus infections, but also provide a basis to evaluate VprBP as novel anti-IAV drug target. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Quantitative Proteomic Approach Identifies Vpr Binding Protein as Novel Host Factor Supporting Influenza A Virus Infections in Human Cells*

PubMed Central

Sadewasser, Anne; Paki, Katharina; Eichelbaum, Katrin; Bogdanow, Boris; Saenger, Sandra; Budt, Matthias; Lesch, Markus; Hinz, Klaus-Peter; Herrmann, Andreas; Meyer, Thomas F.; Karlas, Alexander; Selbach, Matthias; Wolff, Thorsten

2017-01-01

Influenza A virus (IAV) infections are a major cause for respiratory disease in humans, which affects all age groups and contributes substantially to global morbidity and mortality. IAV have a large natural host reservoir in avian species. However, many avian IAV strains lack adaptation to other hosts and hardly propagate in humans. While seasonal or pandemic IAV strains replicate efficiently in permissive human cells, many avian IAV cause abortive nonproductive infections in these hosts despite successful cell entry. However, the precise reasons for these differential outcomes are poorly defined. We hypothesized that the distinct course of an IAV infection with a given virus strain is determined by the differential interplay between specific host and viral factors. By using Spike-in SILAC mass spectrometry-based quantitative proteomics we characterized sets of cellular factors whose abundance is specifically up- or downregulated in the course of permissive versus nonpermissive IAV infection, respectively. This approach allowed for the definition and quantitative comparison of about 3500 proteins in human lung epithelial cells in response to seasonal or low-pathogenic avian H3N2 IAV. Many identified proteins were similarly regulated by both virus strains, but also 16 candidates with distinct changes in permissive versus nonpermissive infection were found. RNAi-mediated knockdown of these differentially regulated host factors identified Vpr binding protein (VprBP) as proviral host factor because its downregulation inhibited efficient propagation of seasonal IAV whereas overexpression increased viral replication of both seasonal and avian IAV. These results not only show that there are similar differences in the overall changes during permissive and nonpermissive influenza virus infections, but also provide a basis to evaluate VprBP as novel anti-IAV drug target. PMID:28289176

Women's Career Success: A Factor Analytic Study of Contributing Factors.

ERIC Educational Resources Information Center

Gaskill, LuAnn Ricketts

1991-01-01

A survey of 466 women employed in retailing received 205 responses identifying (1) factors influencing the success and advancement of women in retailing and (2) how those factors differ for women in upper versus middle positions. Upper-level executives placed more importance on ambition and abilities; midlevel executives credited opportunity and…

Understanding public responses to chemical, biological, radiological and nuclear incidents--driving factors, emerging themes and research gaps.

PubMed

Krieger, Kristian; Amlôt, Richard; Rogers, M Brooke

2014-11-01

This paper discusses the management of public responses to incidents involving chemical, biological, radiological and nuclear materials (CBRN). Given the extraordinary technical and operational challenges of a response to a CBRN release including, but not limited to, hazard detection and identification, casualty decontamination and multi-agency co-ordination, it is not surprising that public psychological and behavioural responses to such incidents have received limited attention by scholars and practitioners alike. As a result, a lack of understanding about the role of the public in effective emergency response constitutes a major gap in research and practice. This limitation must be addressed as a CBRN release has the potential to have wide-reaching psychological and behavioural impacts which, in turn, impact upon public morbidity and mortality rates. This paper addresses a number of key issues: why public responses matter; how responses have been conceptualised by practitioners; what factors have been identified as influencing public responses to a CBRN release and similar extreme events, and what further analysis is needed in order to generate a better understanding of public responses to inform the management of public responses to a CBRN release. Copyright © 2014 Elsevier Ltd. All rights reserved.

Factor Analysis of Therapist-Identified Treatment Targets in Community-Based Children's Mental Health.

PubMed

Love, Allison R; Okado, Izumi; Orimoto, Trina E; Mueller, Charles W

2018-01-01

The present study used exploratory and confirmatory factor analyses to identify underlying latent factors affecting variation in community therapists' endorsement of treatment targets. As part of a statewide practice management program, therapist completed monthly reports of treatment targets (up to 10 per month) for a sample of youth (n = 790) receiving intensive in-home therapy. Nearly 75 % of youth were diagnosed with multiple co-occurring disorders. Five factors emerged: Disinhibition, Societal Rules Evasion, Social Engagement Deficits, Emotional Distress, and Management of Biodevelopmental Outcomes. Using logistic regression, primary diagnosis predicted therapist selection of Disinhibition and Emotional Distress targets. Client age predicted endorsement of Societal Rules Evasion targets. Practice-to-research implications are discussed.

Genome Wide Identification and Characterization of Apple bHLH Transcription Factors and Expression Analysis in Response to Drought and Salt Stress.

PubMed

Mao, Ke; Dong, Qinglong; Li, Chao; Liu, Changhai; Ma, Fengwang

2017-01-01

The bHLH (basic helix-loop-helix) transcription factor family is the second largest in plants. It occurs in all three eukaryotic kingdoms, and plays important roles in regulating growth and development. However, family members have not previously been studied in apple. Here, we identified 188 MdbHLH proteins in apple "Golden Delicious" ( Malus × domestica Borkh.), which could be classified into 18 groups. We also investigated the gene structures and 12 conserved motifs in these MdbHLH s. Coupled with expression analysis and protein interaction network prediction, we identified several genes that might be responsible for abiotic stress responses. This study provides insight and rich resources for subsequent investigations of such proteins in apple.

Genome Wide Identification and Characterization of Apple bHLH Transcription Factors and Expression Analysis in Response to Drought and Salt Stress

PubMed Central

Mao, Ke; Dong, Qinglong; Li, Chao; Liu, Changhai; Ma, Fengwang

2017-01-01

The bHLH (basic helix-loop-helix) transcription factor family is the second largest in plants. It occurs in all three eukaryotic kingdoms, and plays important roles in regulating growth and development. However, family members have not previously been studied in apple. Here, we identified 188 MdbHLH proteins in apple “Golden Delicious” (Malus × domestica Borkh.), which could be classified into 18 groups. We also investigated the gene structures and 12 conserved motifs in these MdbHLHs. Coupled with expression analysis and protein interaction network prediction, we identified several genes that might be responsible for abiotic stress responses. This study provides insight and rich resources for subsequent investigations of such proteins in apple. PMID:28443104

Transcriptional regulation of the operon encoding stress-responsive ECF sigma factor SigH and its anti-sigma factor RshA, and control of its regulatory network in Corynebacterium glutamicum

PubMed Central

2012-01-01

Background The expression of genes in Corynebacterium glutamicum, a Gram-positive non-pathogenic bacterium used mainly for the industrial production of amino acids, is regulated by seven different sigma factors of RNA polymerase, including the stress-responsive ECF-sigma factor SigH. The sigH gene is located in a gene cluster together with the rshA gene, putatively encoding an anti-sigma factor. The aim of this study was to analyze the transcriptional regulation of the sigH and rshA gene cluster and the effects of RshA on the SigH regulon, in order to refine the model describing the role of SigH and RshA during stress response. Results Transcription analyses revealed that the sigH gene and rshA gene are cotranscribed from four sigH housekeeping promoters in C. glutamicum. In addition, a SigH-controlled rshA promoter was found to only drive the transcription of the rshA gene. To test the role of the putative anti-sigma factor gene rshA under normal growth conditions, a C. glutamicum rshA deletion strain was constructed and used for genome-wide transcription profiling with DNA microarrays. In total, 83 genes organized in 61 putative transcriptional units, including those previously detected using sigH mutant strains, exhibited increased transcript levels in the rshA deletion mutant compared to its parental strain. The genes encoding proteins related to disulphide stress response, heat stress proteins, components of the SOS-response to DNA damage and proteasome components were the most markedly upregulated gene groups. Altogether six SigH-dependent promoters upstream of the identified genes were determined by primer extension and a refined consensus promoter consisting of 45 original promoter sequences was constructed. Conclusions The rshA gene codes for an anti-sigma factor controlling the function of the stress-responsive sigma factor SigH in C. glutamicum. Transcription of rshA from a SigH-dependent promoter may serve to quickly shutdown the SigH-dependent stress

Transcriptional regulation of the operon encoding stress-responsive ECF sigma factor SigH and its anti-sigma factor RshA, and control of its regulatory network in Corynebacterium glutamicum.

PubMed

Busche, Tobias; Silar, Radoslav; Pičmanová, Martina; Pátek, Miroslav; Kalinowski, Jörn

2012-09-03

The expression of genes in Corynebacterium glutamicum, a Gram-positive non-pathogenic bacterium used mainly for the industrial production of amino acids, is regulated by seven different sigma factors of RNA polymerase, including the stress-responsive ECF-sigma factor SigH. The sigH gene is located in a gene cluster together with the rshA gene, putatively encoding an anti-sigma factor. The aim of this study was to analyze the transcriptional regulation of the sigH and rshA gene cluster and the effects of RshA on the SigH regulon, in order to refine the model describing the role of SigH and RshA during stress response. Transcription analyses revealed that the sigH gene and rshA gene are cotranscribed from four sigH housekeeping promoters in C. glutamicum. In addition, a SigH-controlled rshA promoter was found to only drive the transcription of the rshA gene. To test the role of the putative anti-sigma factor gene rshA under normal growth conditions, a C. glutamicum rshA deletion strain was constructed and used for genome-wide transcription profiling with DNA microarrays. In total, 83 genes organized in 61 putative transcriptional units, including those previously detected using sigH mutant strains, exhibited increased transcript levels in the rshA deletion mutant compared to its parental strain. The genes encoding proteins related to disulphide stress response, heat stress proteins, components of the SOS-response to DNA damage and proteasome components were the most markedly upregulated gene groups. Altogether six SigH-dependent promoters upstream of the identified genes were determined by primer extension and a refined consensus promoter consisting of 45 original promoter sequences was constructed. The rshA gene codes for an anti-sigma factor controlling the function of the stress-responsive sigma factor SigH in C. glutamicum. Transcription of rshA from a SigH-dependent promoter may serve to quickly shutdown the SigH-dependent stress response after the cells have

Identifying Noncognitive Skills That Contribute to Dental Students' Success: Dental Faculty Perspectives.

PubMed

Virtue, Shannon Myers; Pendergast, Laura; Tellez, Marisol; Waldron, Elizabeth; Ismail, Amid

2017-03-01

The aims of this study were to identify noncognitive factors that dental faculty members perceived to contribute to dental students' success and to assess dental faculty members' ratings of the relative importance of these factors to academic performance, clinical performance, and overall success. Out of 184 eligible faculty members at one U.S. dental school, 43 respondents (23.3%) completed a survey in 2015-16. The survey asked respondents to rank the importance of seven noncognitive factors to academic performance, clinical performance, and overall success. Descriptive analysis was conducted to determine the ratings on importance of each noncognitive factor. Two additional open-ended questions asked faculty members to 1) think of dental students who performed very well and list the noncognitive factors they believed contributed to those students' success and 2) identify the two most important of those factors that contributed to success. Qualitative analysis was conducted to identify themes in the open-ended responses. The respondents rated professionalism and preparedness highest in importance for overall success. Preparedness was rated highest in importance for academic performance, and communication was highest in importance for clinical performance. Six themes were identified in the open-ended responses: communication/interpersonal skills, approach to learning, personal characteristics, professionalism, diverse experiences, and technical abilities. On both open-ended items, the most frequently cited noncognitive skill was communication/interpersonal skills followed by approach to learning. In this study, dental faculty members perceived communication, preparedness, and professionalism as important skills contributing to dental students' success.

DNA Damage Response Factors from Diverse Pathways, Including DNA Crosslink Repair, Mediate Alternative End Joining

PubMed Central

Howard, Sean M.; Yanez, Diana A.; Stark, Jeremy M.

2015-01-01

Alternative end joining (Alt-EJ) chromosomal break repair involves bypassing classical non-homologous end joining (c-NHEJ), and such repair causes mutations often with microhomology at the repair junction. Since the mediators of Alt-EJ are not well understood, we have sought to identify DNA damage response (DDR) factors important for this repair event. Using chromosomal break reporter assays, we surveyed an RNAi library targeting known DDR factors for siRNAs that cause a specific decrease in Alt-EJ, relative to an EJ event that is a composite of Alt-EJ and c-NHEJ (Distal-EJ between two tandem breaks). From this analysis, we identified several DDR factors that are specifically important for Alt-EJ relative to Distal-EJ. While these factors are from diverse pathways, we also found that most of them also promote homologous recombination (HR), including factors important for DNA crosslink repair, such as the Fanconi Anemia factor, FANCA. Since bypass of c-NHEJ is likely important for both Alt-EJ and HR, we disrupted the c-NHEJ factor Ku70 in Fanca-deficient mouse cells and found that Ku70 loss significantly diminishes the influence of Fanca on Alt-EJ. In contrast, an inhibitor of poly ADP-ribose polymerase (PARP) causes a decrease in Alt-EJ that is enhanced by Ku70 loss. Additionally, the helicase/nuclease DNA2 appears to have distinct effects from FANCA and PARP on both Alt-EJ, as well as end resection. Finally, we found that the proteasome inhibitor Bortezomib, a cancer therapeutic that has been shown to disrupt FANC signaling, causes a significant reduction in both Alt-EJ and HR, relative to Distal-EJ, as well as a substantial loss of end resection. We suggest that several distinct DDR functions are important for Alt-EJ, which include promoting bypass of c-NHEJ and end resection. PMID:25629353

Identifying RNA splicing factors using IFT genes in Chlamydomonas reinhardtii.

PubMed

Lin, Huawen; Zhang, Zhengyan; Iomini, Carlo; Dutcher, Susan K

2018-03-01

Intraflagellar transport moves proteins in and out of flagella/cilia and it is essential for the assembly of these organelles. Using whole-genome sequencing, we identified splice site mutations in two IFT genes, IFT81 ( fla9 ) and IFT121 ( ift121-2 ), which lead to flagellar assembly defects in the unicellular green alga Chlamydomonas reinhardtii The splicing defects in these ift mutants are partially corrected by mutations in two conserved spliceosome proteins, DGR14 and FRA10. We identified a dgr14 deletion mutant, which suppresses the 3' splice site mutation in IFT81 , and a frameshift mutant of FRA10 , which suppresses the 5' splice site mutation in IFT121 Surprisingly, we found dgr14-1 and fra10 mutations suppress both splice site mutations. We suggest these two proteins are involved in facilitating splice site recognition/interaction; in their absence some splice site mutations are tolerated. Nonsense mutations in SMG1 , which is involved in nonsense-mediated decay, lead to accumulation of aberrant transcripts and partial restoration of flagellar assembly in the ift mutants. The high density of introns and the conservation of noncore splicing factors, together with the ease of scoring the ift mutant phenotype, make Chlamydomonas an attractive organism to identify new proteins involved in splicing through suppressor screening. © 2018 The Authors.

Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction

PubMed Central

Mano, Miguel; Ippodrino, Rudy; Zentilin, Lorena; Zacchigna, Serena; Giacca, Mauro

2015-01-01

Viral vectors based on the adeno-associated virus (AAV) hold great promise for in vivo gene transfer; several unknowns, however, still limit the vectors’ broader and more efficient application. Here, we report the results of a high-throughput, whole-genome siRNA screening aimed at identifying cellular factors regulating AAV transduction. We identified 1,483 genes affecting vector efficiency more than 4-fold and up to 50-fold, either negatively or positively. Most of these factors have not previously been associated to AAV infection. The most effective siRNAs were independent from the virus serotype or analyzed cell type and were equally evident for single-stranded and self-complementary AAV vectors. A common characteristic of the most effective siRNAs was the induction of cellular DNA damage and activation of a cell cycle checkpoint. This information can be exploited for the development of more efficient AAV-based gene delivery procedures. Administration of the most effective siRNAs identified by the screening to the liver significantly improved in vivo AAV transduction efficiency. PMID:26305933

A multi-factor GIS method to identify optimal geographic locations for electric vehicle (EV) charging stations

NASA Astrophysics Data System (ADS)

Zhang, Yongqin; Iman, Kory

2018-05-01

Fuel-based transportation is one of the major contributors to poor air quality in the United States. Electric Vehicle (EV) is potentially the cleanest transportation technology to our environment. This research developed a spatial suitability model to identify optimal geographic locations for installing EV charging stations for travelling public. The model takes into account a variety of positive and negative factors to identify prime locations for installing EV charging stations in Wasatch Front, Utah, where automobile emission causes severe air pollution due to atmospheric inversion condition near the valley floor. A walkable factor grid was created to store index scores from input factor layers to determine prime locations. 27 input factors including land use, demographics, employment centers etc. were analyzed. Each factor layer was analyzed to produce a summary statistic table to determine the site suitability. Potential locations that exhibit high EV charging usage were identified and scored. A hot spot map was created to demonstrate high, moderate, and low suitability areas for installing EV charging stations. A spatially well distributed EV charging system was then developed, aiming to reduce "range anxiety" from traveling public. This spatial methodology addresses the complex problem of locating and establishing a robust EV charging station infrastructure for decision makers to build a clean transportation infrastructure, and eventually improve environment pollution.

Prediction of response to PPI therapy and factors influencing treatment outcome in patients with GORD: a prospective pragmatic trial using pantoprazole

PubMed Central

2011-01-01

Background Management of patients with gastro-oesophageal reflux disease (GORD) can be assisted by information predicting the likely response to proton pump inhibitor (PPI) treatment. The aim was to undertake a study of GORD patients designed to approximate ordinary clinical practice that would identify patient characteristics predicting symptomatic response to pantoprazole treatment. Methods 1888 patients with symptoms of GORD were enrolled in a multicentre, multinational, prospective, open study of 8 weeks pantoprazole treatment, 40 mg daily. Response was assessed by using the ReQuest™ questionnaire, by the investigator making conventional clinical enquiry and by asking patients about their satisfaction with symptom control. Factors including pre-treatment oesophagitis, gender, age, body mass index (BMI), Helicobacter pylori status, anxiety and depression, and concurrent IBS symptoms were examined using logistic regression to determine if they were related to response, judged from the ReQuest™-GI score. Results Poorer treatment responses were associated with non-erosive reflux disease, female gender, lower BMI, anxiety and concurrent irritable bowel syndrome symptoms before treatment. No association was found with age, Helicobacter pylori status or oesophagitis grade. Some reflux-related symptoms were still present in 14% of patients who declared themselves 'well-satisfied' with their symptom control. Conclusions Some readily identifiable features help to predict symptomatic responses to a PPI and consequently may help in managing patient expectation. ClinicalTrial.gov identifier: NCT00312806. PMID:21569313

Identifying the Factors That Predict Degree Completion for Entirely Online Community College Students

ERIC Educational Resources Information Center

Brock, Kishia R.

2014-01-01

The purpose of this research study was to identify demographic characteristics, academic factors, and student behaviors that contributed to successful degree and certificate completion for entirely online, nontraditional undergraduate students at a large community college. A discrete-time event history analysis was used to model the retention of…

Factors that deregulate the protective immune response in tuberculosis.

PubMed

Hernandez-Pando, Rogelio; Orozco, Hector; Aguilar, Diana

2009-01-01

Tuberculosis (TB) is a chronic infectious disease which essentially affects the lungs and produces profound abnormalities on the immune system. Although most people infected by the tubercle bacillus (90%) do not develop the disease during their lifetime, when there are alterations in the immune system, such as co-infection with HIV, malnutrition, or diabetes, the risk of developing active disease increases considerably. Interestingly, during the course of active disease, even in the absence of immunosuppressive conditions, there is a profound and prolonged suppression of Mycobacterium tuberculosis-specific protective immune responses. Several immune factors can contribute to downregulate the protective immunity, permitting disease progression. In general, many of these factors are potent anti-inflammatory molecules that are probably overproduced with the intention to protect against tissue damage, but the consequence of this response is a decline in protective immunity facilitating bacilli growth and disease progression. Here the most significant participants in protective immunity are reviewed, in particular the factors that deregulate protective immunity in TB. Their manipulation as novel forms of immunotherapy are also briefly commented.

Effects of exposure to factor concentrates containing donations from identified AIDS patients

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

Jason, J.; Holman, R.C.; Dixon, G.

1986-10-03

The authors recipients of eight lots of factors VII and IX voluntarily withdrawn from distribution because one donor was known to have subsequently developed the acquired immunodeficiency syndrome with a nonexposed cohort matched by age, sex, and factor use. The factor VIII recipient cohorts did not differ in prevalence of antibody to human immunodeficiency virus (HIV), T-cell subset numbers, T-helper to T-suppressor ratios, or immunogloubulin levels. Exposed individuals had higher levels of immune complexes by C1q binding and staphylococcal binding assays and lower responses to phytohemagglutinin and concanavalin A. However, only the staphylococcal binding assay values were outside the normalmore » range for our laboratory. Factor IX recipient cohorts did not differ in HIV antibody prevalence or any immune tests. Although exposed and nonexposed individuals did not differ from each other in a clinically meaningful fashion at initial testing, both the exposed and nonexposed cohorts had high rats of HIV seroprevalence. Market withdrawals were clearly insufficient means of limiting the spread of HIV in hemophilic patients; however, the currently available methods of donor screening and viral inactivation of blood products will prevent continued exposed within this population.« less

Identifying novel genetic determinants of hemostatic balance.

PubMed

Ginsburg, D

2005-08-01

Incomplete penetrance and variable expressivity confound the diagnosis and therapy of most inherited thrombotic and hemorrhagic disorders. For many of these diseases, some or most of this variability is determined by genetic modifiers distinct from the primary disease gene itself. Clues toward identifying such modifier genes may come from studying rare Mendelian disorders of hemostasis. Examples include identification of the cause of combined factor V and VIII deficiency as mutations in the ER Golgi intermediate compartment proteins LMAN1 and MCFD2. These proteins form a cargo receptor that facilitates the transport of factors V and VIII, and presumably other proteins, from the ER to the Golgi. A similar positional cloning approach identified ADAMTS-13 as the gene responsible for familial TTP. Along with the work of many other groups, these findings identified VWF proteolysis by ADAMTS-13 as a key regulatory pathway for hemostasis. Recent advances in mouse genetics also provide powerful tools for the identification of novel genes contributing to hemostatic balance. Genetic studies of inbred mouse lines with unusually high and unusually low plasma VWF levels identified polymorphic variation in the expression of a glycosyltransferase gene, Galgt2, as an important determinant of plasma VWF levels in the mouse. Ongoing studies in mice genetically engineered to carry the factor V Leiden mutation may similarly identify novel genes contributing to thrombosis risk in humans.

WRKY transcription factors in plant responses to stresses.

PubMed

Jiang, Jingjing; Ma, Shenghui; Ye, Nenghui; Jiang, Ming; Cao, Jiashu; Zhang, Jianhua

2017-02-01

The WRKY gene family is among the largest families of transcription factors (TFs) in higher plants. By regulating the plant hormone signal transduction pathway, these TFs play critical roles in some plant processes in response to biotic and abiotic stress. Various bodies of research have demonstrated the important biological functions of WRKY TFs in plant response to different kinds of biotic and abiotic stresses and working mechanisms. However, very little summarization has been done to review their research progress. Not just important TFs function in plant response to biotic and abiotic stresses, WRKY also participates in carbohydrate synthesis, senescence, development, and secondary metabolites synthesis. WRKY proteins can bind to W-box (TGACC (A/T)) in the promoter of its target genes and activate or repress the expression of downstream genes to regulate their stress response. Moreover, WRKY proteins can interact with other TFs to regulate plant defensive responses. In the present review, we focus on the structural characteristics of WRKY TFs and the research progress on their functions in plant responses to a variety of stresses. © 2016 Institute of Botany, Chinese Academy of Sciences.

Host, vehicular and environmental factors responsible for road traffic crashes in a Nigerian city: identifiable issues for road traffic injury control.

PubMed

Adeoye, Peter Oladapo; Kadri, Dotun Musiliu; Bello, Jibril Oyekunle; Ofoegbu, Chima Kingsley Pascal; Abdur-Rahman, Lukman Olajide; Adekanye, Adedeji Olugbenga; Solagberu, Babatunde Akeeb

2014-01-01

Road traffic injury (RTI) has assumed major public health importance world-wide and the burden is heavier on the health-care infrastructure of countries in Sub-Saharan Africa. In Nigeria, RTI is the leading cause of trauma related morbidity and mortality. While there are some published epidemiological reports on RTI in the region, studies on the mechanism of causation of road traffic crashes (RTC) are not available. Over a 9-month period, we prospectively captured the 571 victims of RTC presenting to a single tertiary health care center in Nigeria. Data collected include demographic data, Mechanism of causation of RTC, Injuries sustained and outcomes. Over three-quarters of the victims are young people and half were either traders (27.5%) or students (20%). Pedestrians, motorcycle riders and open truck occupants (people sitting at the rear loading compartment of trucks) often had fatal injuries. Analysis of collision patterns showed that lone crashes were the most frequent though car-to-motorcycle crashes caused a quarter of the deaths. Host factors (over-speeding driver, driver misjudgment, sleeping driver etc.) were responsible for four-fifths of the crashes while vehicular and environmental factors accounted for the remaining. On binary regression analysis, head injured victims had higher odds of dying than the non-head injured (Odds ratio = 6.5). This paper elucidates the mechanisms of causation of and types of injuries sustained following RTC in Nigeria and thus provide opportunities for prevention and control of this unacceptable situation.

Factors responsible for performance on the day-night task: response set or semantics?

PubMed

Simpson, Andrew; Riggs, Kevin J

2005-07-01

In a recent study Diamond, Kirkham and Amso (2002) obtained evidence consistent with the claim that the day-night task requires inhibition because the picture and its corresponding conflicting response are semantically related. In their study children responded more accurately in a dog-pig condition (see /day picture/ say "dog"; see /night picture/ say "pig") than the standard day-night condition (see /day picture/ say "night"; see /night picture/ say "day"). However, there is another effect that may have made the day-night condition harder than the dog-pig condition: the response set effect. In the day-night condition the names of the two stimuli ("day" and "night") and the two corresponding conflicting responses ("night" and "day") are from the same response set: both "day" and "night". In the dog-pig condition the names of the stimuli ("day", "night") and the corresponding responses ("dog", "pig") are from a different response set. In two experiments (Experiment 1 with 4-year-olds (n = 25); Experiment 2 with , 4-, 5-, 7- and 11-year-olds (n = 81)) children were tested on four experimental conditions that enabled the effects of semantics and response set to be separated. Overall, our data suggest that response set is a major factor in creating the inhibitory demands of the day-night task in children of all ages. Results are discussed in relation to other inhibitory tasks.

Baseline Factors Predicting Placebo Response to Treatment in Children and Adolescents With Autism Spectrum Disorders

PubMed Central

King, Bryan H.; Dukes, Kimberly; Donnelly, Craig L.; Sikich, Linmarie; McCracken, James T.; Scahill, Lawrence; Hollander, Eric; Bregman, Joel D.; Anagnostou, Evdokia; Robinson, Fay; Sullivan, Lisa; Hirtz, Deborah

2016-01-01

IMPORTANCE The finding of factors that differentially predict the likelihood of response to placebo over that of an active drug could have a significant impact on study design in this population. OBJECTIVE To identify possible nonspecific, baseline predictors of response to intervention in a large randomized clinical trial of children and adolescents with autism spectrum disorders. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of citalopram hydrobromide for children and adolescents with autism spectrum disorders and prominent repetitive behavior. Baseline data at study entry were examined with respect to final outcome to determine if response predictors could be identified. A total of 149 children and adolescents 5 to 17 years of age (mean [SD] age, 9.4 [3.1] years) from 6 academic centers were randomly assigned to citalopram (n = 73) or placebo (n = 76). Participants had autistic disorder, Asperger syndrome, or pervasive developmental disorder, not otherwise specified; had illness severity ratings that were moderate or more than moderate on the Clinical Global Impression–Severity scale; and scored moderate or more than moderate on compulsive behaviors measured with the modified Children’s Yale-Brown Obsessive-Compulsive Scale. INTERVENTIONS Twelve weeks of treatment with citalopram (10 mg/5 mL) or placebo. The mean (SD) maximum dose of citalopram was 16.5 (6.5) mg by mouth daily (maximum dose, 20 mg/d). MAIN OUTCOMES AND MEASURES A positive response was defined as having a score of at least much improved on the Clinical Global Impression–Improvement scale at week 12. Baseline measures included demographic (sex, age, weight, and pubertal status), clinical, and family measures. Clinical variables included baseline illness severity ratings (the Aberrant Behavior Checklist, the Child and Adolescent Symptom Inventory, the Vineland Adaptive Behavior Scales, the Repetitive Behavior Scale–Revised, and the Children’s Yale-Brown Obsessive

The in vitro real-time oscillation monitoring system identifies potential entrainment factors for circadian clocks

PubMed Central

Nakahata, Yasukazu; Akashi, Makoto; Trcka, Daniel; Yasuda, Akio; Takumi, Toru

2006-01-01

Background Circadian rhythms are endogenous, self-sustained oscillations with approximately 24-hr rhythmicity that are manifested in various physiological and metabolic processes. The circadian organization of these processes in mammals is governed by the master oscillator within the suprachiasmatic nuclei (SCN) of the hypothalamus. Recent findings revealed that circadian oscillators exist in most organs, tissues, and even in immortalized cells, and that the oscillators in peripheral tissues are likely to be coordinated by SCN, the master oscillator. Some candidates for endogenous entrainment factors have sporadically been reported, however, their details remain mainly obscure. Results We developed the in vitro real-time oscillation monitoring system (IV-ROMS) by measuring the activity of luciferase coupled to the oscillatory gene promoter using photomultiplier tubes and applied this system to screen and identify factors able to influence circadian rhythmicity. Using this IV-ROMS as the primary screening of entrainment factors for circadian clocks, we identified 12 candidates as the potential entrainment factor in a total of 299 peptides and bioactive lipids. Among them, four candidates (endothelin-1, all-trans retinoic acid, 9-cis retinoic acid, and 13-cis retinoic acid) have already been reported as the entrainment factors in vivo and in vitro. We demonstrated that one of the novel candidates, 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a natural ligand of the peroxisome proliferator-activated receptor-γ (PPAR-γ), triggers the rhythmic expression of endogenous clock genes in NIH3T3 cells. Furthermore, we showed that 15d-PGJ2 transiently induces Cry1, Cry2, and Rorα mRNA expressions and that 15d-PGJ2-induced entrainment signaling pathway is PPAR-γ – and MAPKs (ERK, JNK, p38MAPK)-independent. Conclusion Here, we identified 15d-PGJ2 as an entrainment factor in vitro. Using our developed IV-ROMS to screen 299 compounds, we found eight novel and four known

Identifying Risk and Protective Factors in Recidivist Juvenile Offenders: A Decision Tree Approach

PubMed Central

Ortega-Campos, Elena; García-García, Juan; Gil-Fenoy, Maria José; Zaldívar-Basurto, Flor

2016-01-01

Research on juvenile justice aims to identify profiles of risk and protective factors in juvenile offenders. This paper presents a study of profiles of risk factors that influence young offenders toward committing sanctionable antisocial behavior (S-ASB). Decision tree analysis is used as a multivariate approach to the phenomenon of repeated sanctionable antisocial behavior in juvenile offenders in Spain. The study sample was made up of the set of juveniles who were charged in a court case in the Juvenile Court of Almeria (Spain). The period of study of recidivism was two years from the baseline. The object of study is presented, through the implementation of a decision tree. Two profiles of risk and protective factors are found. Risk factors associated with higher rates of recidivism are antisocial peers, age at baseline S-ASB, problems in school and criminality in family members. PMID:27611313

Sequence and Expression Analyses of Ethylene Response Factors Highly Expressed in Latex Cells from Hevea brasiliensis

PubMed Central

Piyatrakul, Piyanuch; Yang, Meng; Putranto, Riza-Arief; Pirrello, Julien; Dessailly, Florence; Hu, Songnian; Summo, Marilyne; Theeravatanasuk, Kannikar; Leclercq, Julie; Kuswanhadi; Montoro, Pascal

2014-01-01

The AP2/ERF superfamily encodes transcription factors that play a key role in plant development and responses to abiotic and biotic stress. In Hevea brasiliensis, ERF genes have been identified by RNA sequencing. This study set out to validate the number of HbERF genes, and identify ERF genes involved in the regulation of latex cell metabolism. A comprehensive Hevea transcriptome was improved using additional RNA reads from reproductive tissues. Newly assembled contigs were annotated in the Gene Ontology database and were assigned to 3 main categories. The AP2/ERF superfamily is the third most represented compared with other transcription factor families. A comparison with genomic scaffolds led to an estimation of 114 AP2/ERF genes and 1 soloist in Hevea brasiliensis. Based on a phylogenetic analysis, functions were predicted for 26 HbERF genes. A relative transcript abundance analysis was performed by real-time RT-PCR in various tissues. Transcripts of ERFs from group I and VIII were very abundant in all tissues while those of group VII were highly accumulated in latex cells. Seven of the thirty-five ERF expression marker genes were highly expressed in latex. Subcellular localization and transactivation analyses suggested that HbERF-VII candidate genes encoded functional transcription factors. PMID:24971876

Sequence and expression analyses of ethylene response factors highly expressed in latex cells from Hevea brasiliensis.

PubMed

Piyatrakul, Piyanuch; Yang, Meng; Putranto, Riza-Arief; Pirrello, Julien; Dessailly, Florence; Hu, Songnian; Summo, Marilyne; Theeravatanasuk, Kannikar; Leclercq, Julie; Kuswanhadi; Montoro, Pascal

2014-01-01

The AP2/ERF superfamily encodes transcription factors that play a key role in plant development and responses to abiotic and biotic stress. In Hevea brasiliensis, ERF genes have been identified by RNA sequencing. This study set out to validate the number of HbERF genes, and identify ERF genes involved in the regulation of latex cell metabolism. A comprehensive Hevea transcriptome was improved using additional RNA reads from reproductive tissues. Newly assembled contigs were annotated in the Gene Ontology database and were assigned to 3 main categories. The AP2/ERF superfamily is the third most represented compared with other transcription factor families. A comparison with genomic scaffolds led to an estimation of 114 AP2/ERF genes and 1 soloist in Hevea brasiliensis. Based on a phylogenetic analysis, functions were predicted for 26 HbERF genes. A relative transcript abundance analysis was performed by real-time RT-PCR in various tissues. Transcripts of ERFs from group I and VIII were very abundant in all tissues while those of group VII were highly accumulated in latex cells. Seven of the thirty-five ERF expression marker genes were highly expressed in latex. Subcellular localization and transactivation analyses suggested that HbERF-VII candidate genes encoded functional transcription factors.

What Factors Affect Response to Ads? A Perspective.

ERIC Educational Resources Information Center

Rotzoll, Kim B.

The concept of "frame of reference" offers a perspective from which to examine the many factors which affect advertising response. The advertiser is interested in affecting two types of overt behavior. First, the individual is induced to select a particular stimulus (the advertisement) from competing stimuli (such as other people, noise,…

Heat shock factor 1 suppresses the HIV-induced inflammatory response by inhibiting nuclear factor-κB.

PubMed

Pan, Xiaoyan; Lin, Jian; Zeng, Xiaoyun; Li, Wenjuan; Wu, Wenjiao; Lu, Wan Zhen; Liu, Jing; Liu, Shuwen

2018-05-01

The persistent inflammation aggravated by a disordered immune response is considered to be the major cause of CD4 + T cell depletion in lymphoid tissue, which impels the progression of AIDS. Here, we report that heat shock factor 1 (HSF1) works as an innate repressor of HIV-induced inflammation. The activation of HSF1 was found to accompany inflammation during HIV infection. Further research uncovered that HSF1 activation inhibited HIV-induced inflammation. In addition, HSF1 overexpression suppressed the inflammatory response induced by HIV, while HSF1 deficiency exacerbated that inflammation. Mechanistically, HSF1 was found to compete with nuclear factor-κB (NF-κB) in the nucleus. Generally, our report highlights that HSF1 is an important host factor in regulating HIV-induced inflammation and may work as a potential target for curing AIDS. Copyright © 2018 Elsevier Inc. All rights reserved.

Auxin Response Factor Genes Repertoire in Mulberry: Identification, and Structural, Functional and Evolutionary Analyses

PubMed Central

Baranwal, Vinay Kumar; Negi, Nisha; Khurana, Paramjit

2017-01-01

Auxin Response Factors (ARFs) are at the core of the regulation mechanism for auxin-mediated responses, along with AUX/IAA proteins.They are critical in the auxin-mediated control of various biological responses including development and stress. A wild mulberry species genome has been sequenced and offers an opportunity to investigate this important gene family. A total of 17 ARFs have been identified from mulberry (Morus notabilis) which show a wide range of expression patterns. Of these 17 ARFs, 15 have strong acidic isoelectric point (pI) values and a molecular mass ranging from 52 kDa to 101 kDa. The putative promoters of these ARFs harbour cis motifs related to light-dependent responses, various stress responses and hormone regulations suggestive of their multifactorial regulation. The gene ontology terms for ARFs indicate their role in flower development, stress, root morphology and other such development and stress mitigation related activities. Conserved motif analysis showed the presence of all typical domains in all but four members that lack the PB1 domain and thus represent truncated ARFs. Expression analysis of these ARFs suggests their preferential expression in tissues ranging from leaf, root, winter bud, bark and male flowers. These ARFs showed differential expression in the leaf tissue of M. notabilis, Morus laevigata and Morus serrata. Insights gained from this analysis have implications in mulberry improvement programs. PMID:28841197

Organisational Issues for E-Learning: Critical Success Factors as Identified by HE Practitioners

ERIC Educational Resources Information Center

McPherson, Maggie; Nunes, Miguel Baptista

2006-01-01

Purpose: The purpose of this paper is to report on a research project that identified organisational critical success factors (CSFs) for e-learning implementation in higher education (HE). These CSFs can be used as a theoretical foundation upon which to base decision-making and strategic thinking about e-learning. Design/methodology/approach: The…

Identifying predictive factors for long-term complications following button battery impactions: A case series and literature review.

PubMed

Eliason, Michael J; Melzer, Jonathan M; Winters, Jessica R; Gallagher, Thomas Q

2016-08-01

To complement a case series review of button battery impactions managed at our single military tertiary care center with a thorough literature review of laboratory research and clinical cases to develop a protocol to optimize patient care. Specifically, to identify predictive factors of long-term complications which can be used by the pediatric otolaryngologist to guide patient management after button battery impactions. A retrospective review of the Department of Defense's electronic medical record systems was conducted to identify patients with button battery ingestions and then characterize their treatment course. A thorough literature review complemented the lessons learned to identify potentially predictive clinical measures for long-term complications. Eight patients were identified as being treated for button battery impaction in the aerodigestive tract with two sustaining long-term complications. The median age of the patients treated was 33 months old and the median estimated time of impaction in the aerodigestive tract prior to removal was 10.5 h. Time of impaction, anatomic direction of the battery's negative pole, and identifying specific battery parameters were identified as factors that may be employed to predict sequelae. Based on case reviews, advancements in battery manufacturing, and laboratory research, there are distinct clinical factors that should be assessed at the time of initial therapy to guide follow-up management to minimize potential catastrophic sequelae of button battery ingestion. Published by Elsevier Ireland Ltd.

Growth factors and growth factor receptors in the hippocampus. Role in plasticity and response to injury.

PubMed

Nieto-Sampedro, M; Bovolenta, P

1990-01-01

Various growth factors are present in the hippocampal formation and appear responsible for the prominent plasticity of this brain area. Although hormone-like growth-promoting polypeptides are the best known, recent studies emphasize the importance in the growth response of molecules such as laminin proteoglycans, neurotransmitters and growth inhibitors. The progress and problems in the study of these substances are reviewed.

Whole Exome Sequencing Identifies Novel Genes for Fetal Hemoglobin Response to Hydroxyurea in Children with Sickle Cell Anemia

PubMed Central

Sheehan, Vivien A.; Crosby, Jacy R.; Sabo, Aniko; Mortier, Nicole A.; Howard, Thad A.; Muzny, Donna M.; Dugan-Perez, Shannon; Aygun, Banu; Nottage, Kerri A.; Boerwinkle, Eric; Gibbs, Richard A.; Ware, Russell E.; Flanagan, Jonathan M.

2014-01-01

Hydroxyurea has proven efficacy in children and adults with sickle cell anemia (SCA), but with considerable inter-individual variability in the amount of fetal hemoglobin (HbF) produced. Sibling and twin studies indicate that some of that drug response variation is heritable. To test the hypothesis that genetic modifiers influence pharmacological induction of HbF, we investigated phenotype-genotype associations using whole exome sequencing of children with SCA treated prospectively with hydroxyurea to maximum tolerated dose (MTD). We analyzed 171 unrelated patients enrolled in two prospective clinical trials, all treated with dose escalation to MTD. We examined two MTD drug response phenotypes: HbF (final %HbF minus baseline %HbF), and final %HbF. Analyzing individual genetic variants, we identified multiple low frequency and common variants associated with HbF induction by hydroxyurea. A validation cohort of 130 pediatric sickle cell patients treated to MTD with hydroxyurea was genotyped for 13 non-synonymous variants with the strongest association with HbF response to hydroxyurea in the discovery cohort. A coding variant in Spalt-like transcription factor, or SALL2, was associated with higher final HbF in this second independent replication sample and SALL2 represents an outstanding novel candidate gene for further investigation. These findings may help focus future functional studies and provide new insights into the pharmacological HbF upregulation by hydroxyurea in patients with SCA. PMID:25360671

Whole exome sequencing identifies novel genes for fetal hemoglobin response to hydroxyurea in children with sickle cell anemia.

PubMed

Sheehan, Vivien A; Crosby, Jacy R; Sabo, Aniko; Mortier, Nicole A; Howard, Thad A; Muzny, Donna M; Dugan-Perez, Shannon; Aygun, Banu; Nottage, Kerri A; Boerwinkle, Eric; Gibbs, Richard A; Ware, Russell E; Flanagan, Jonathan M

2014-01-01

Hydroxyurea has proven efficacy in children and adults with sickle cell anemia (SCA), but with considerable inter-individual variability in the amount of fetal hemoglobin (HbF) produced. Sibling and twin studies indicate that some of that drug response variation is heritable. To test the hypothesis that genetic modifiers influence pharmacological induction of HbF, we investigated phenotype-genotype associations using whole exome sequencing of children with SCA treated prospectively with hydroxyurea to maximum tolerated dose (MTD). We analyzed 171 unrelated patients enrolled in two prospective clinical trials, all treated with dose escalation to MTD. We examined two MTD drug response phenotypes: HbF (final %HbF minus baseline %HbF), and final %HbF. Analyzing individual genetic variants, we identified multiple low frequency and common variants associated with HbF induction by hydroxyurea. A validation cohort of 130 pediatric sickle cell patients treated to MTD with hydroxyurea was genotyped for 13 non-synonymous variants with the strongest association with HbF response to hydroxyurea in the discovery cohort. A coding variant in Spalt-like transcription factor, or SALL2, was associated with higher final HbF in this second independent replication sample and SALL2 represents an outstanding novel candidate gene for further investigation. These findings may help focus future functional studies and provide new insights into the pharmacological HbF upregulation by hydroxyurea in patients with SCA.

Identifying at-risk profiles and protective factors for problem gambling: A longitudinal study across adolescence and early adulthood.

PubMed

Allami, Youssef; Vitaro, Frank; Brendgen, Mara; Carbonneau, René; Tremblay, Richard E

2018-05-01

Past studies have identified various risk and protective factors for problem gambling (PG). However, no study has examined the interplay between these factors using a combination of person-centered and variable-centered approaches embedded within a longitudinal design. The present study aimed to (a) identify distinct profiles in early adolescence based on a set of risk factors commonly associated with PG (impulsivity, depression, anxiety, drug-alcohol use, aggressiveness, and antisociality), (b) explore the difference in reported gambling problems between these profiles during midadolescence and early adulthood, and (c) identify family- and peer-related variables that could operate as protective or compensatory factors in this context. Two samples were used: (a) a population sample (N = 1,033) living in low socioeconomic-status neighborhoods and (b) a population sample (N = 3,017) representative of students attending Quebec schools. Latent profile analyses were conducted to identify at-risk profiles based on individual risk factors measured at age 12 years. Negative binomial regression models were estimated to compare profiles in terms of their reported gambling problems at ages 16 and 23. Finally, family- and peer-related variables measured at age 14 were included to test their protective or compensatory role with respect to the link between at-risk profiles and gambling problems. Four profiles were identified: well-adjusted, internalizing, externalizing, and comorbid. Compared to the well-adjusted profile, the externalizing and comorbid profiles reported more gambling problems at ages 16 and 23, but the internalizing profile did not differ significantly. Various protective and compensatory factors emerged for each profile at both time points. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Rhodopseudomonas palustris CGA010 Proteome Implicates Extracytoplasmic Function Sigma Factor in Stress Response

DOE PAGES

Allen, Michael S.; Hurst, Gregory B.; Lu, Tse-Yuan S.; ...

2015-04-08

Rhodopseudomonas palustris encodes 16 extracytoplasmic function (ECF) σ factors. In this paper, to begin to investigate the regulatory network of one of these ECF σ factors, the whole proteome of R. palustris CGA010 was quantitatively analyzed by tandem mass spectrometry from cultures episomally expressing the ECF σ RPA4225 (ecfT) versus a WT control. Among the proteins with the greatest increase in abundance were catalase KatE, trehalose synthase, a DPS-like protein, and several regulatory proteins. Alignment of the cognate promoter regions driving expression of several upregulated proteins suggested a conserved binding motif in the -35 and -10 regions with the consensusmore » sequence GGAAC-18N-TT. Additionally, the putative anti-σ factor RPA4224, whose gene is contained in the same predicted operon as RPA4225, was identified as interacting directly with the predicted response regulator RPA4223 by mass spectrometry of affinity-isolated protein complexes. Furthermore, another gene (RPA4226) coding for a protein that contains a cytoplasmic histidine kinase domain is located immediately upstream of RPA4225. The genomic organization of orthologs for these four genes is conserved in several other strains of R. palustris as well as in closely related α-Proteobacteria. Finally, taken together, these data suggest that ECF σ RPA4225 and the three additional genes make up a sigma factor mimicry system in R. palustris.« less

Rhodopseudomonas palustris CGA010 Proteome Implicates Extracytoplasmic Function Sigma Factor in Stress Response

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

Allen, Michael S.; Hurst, Gregory B.; Lu, Tse-Yuan S.

Rhodopseudomonas palustris encodes 16 extracytoplasmic function (ECF) σ factors. In this paper, to begin to investigate the regulatory network of one of these ECF σ factors, the whole proteome of R. palustris CGA010 was quantitatively analyzed by tandem mass spectrometry from cultures episomally expressing the ECF σ RPA4225 (ecfT) versus a WT control. Among the proteins with the greatest increase in abundance were catalase KatE, trehalose synthase, a DPS-like protein, and several regulatory proteins. Alignment of the cognate promoter regions driving expression of several upregulated proteins suggested a conserved binding motif in the -35 and -10 regions with the consensusmore » sequence GGAAC-18N-TT. Additionally, the putative anti-σ factor RPA4224, whose gene is contained in the same predicted operon as RPA4225, was identified as interacting directly with the predicted response regulator RPA4223 by mass spectrometry of affinity-isolated protein complexes. Furthermore, another gene (RPA4226) coding for a protein that contains a cytoplasmic histidine kinase domain is located immediately upstream of RPA4225. The genomic organization of orthologs for these four genes is conserved in several other strains of R. palustris as well as in closely related α-Proteobacteria. Finally, taken together, these data suggest that ECF σ RPA4225 and the three additional genes make up a sigma factor mimicry system in R. palustris.« less

Meta-analysis of genome-wide association studies identifies genetic risk factors for stroke in African-Americans

PubMed Central

Carty, Cara L.; Keene, Keith L.; Cheng, Yu-Ching; Meschia, James F.; Chen, Wei-Min; Nalls, Mike; Bis, Joshua C.; Kittner, Steven J.; Rich, Stephen S.; Tajuddin, Salman; Zonderman, Alan B.; Evans, Michele K.; Langefeld, Carl D.; Gottesman, Rebecca; Mosley, Thomas H.; Shahar, Eyal; Woo, Daniel; Yaffe, Kristine; Liu, YongMei; Sale, Michèle M.; Dichgans, Martin; Malik, Rainer; Longstreth, WT; Mitchell, Braxton D.; Psaty, Bruce M.; Kooperberg, Charles; Reiner, Alexander; Worrall, Bradford B.; Fornage, Myriam

2015-01-01

Background and Purpose The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African-Americans despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population genome-wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. Methods Using METAL, we conducted meta-analyses of GWAS in 14,746 African-Americans (1,365 ischemic and 1,592 total stroke cases) from COMPASS, and tested SNPs with P<10−6 for validation in METASTROKE, a consortium of ischemic stroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. Results The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613, P=3.9×10−8) in African-Americans. Nominal associations (P<10−6) for total or ischemic stroke were observed for 18 variants in or near genes implicated in cell cycle/ mRNA pre-splicing (PTPRG, CDC5L), platelet function (HPS4), blood-brain barrier permeability (CLDN17), immune response (ELTD1, WDFY4, IL1F10-IL1RN), and histone modification (HDAC9). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 (P=0.03), and 1p31.1 (P=0.018). Four of 7 previously reported ischemic stroke loci (PITX2, HDAC9, CDKN2A/CDKN2B and ZFHX3) were nominally associated (P<0.05) with stroke in COMPASS. Conclusions We identified a novel SNP associated with total stroke in African-Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African-Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations. PMID:26089329

Factor analysis in the Genetics of Asthma International Network family study identifies five major quantitative asthma phenotypes.

PubMed

Pillai, S G; Tang, Y; van den Oord, E; Klotsman, M; Barnes, K; Carlsen, K; Gerritsen, J; Lenney, W; Silverman, M; Sly, P; Sundy, J; Tsanakas, J; von Berg, A; Whyte, M; Ortega, H G; Anderson, W H; Helms, P J

2008-03-01

Asthma is a clinically heterogeneous disease caused by a complex interaction between genetic susceptibility and diverse environmental factors. In common with other complex diseases the lack of a standardized scheme to evaluate the phenotypic variability poses challenges in identifying the contribution of genes and environments to disease expression. To determine the minimum number of sets of features required to characterize subjects with asthma which will be useful in identifying important genetic and environmental contributors. Methods Probands aged 7-35 years with physician diagnosed asthma and symptomatic siblings were identified in 1022 nuclear families from 11 centres in six countries forming the Genetics of Asthma International Network. Factor analysis was used to identify distinct phenotypes from questionnaire, clinical, and laboratory data, including baseline pulmonary function, allergen skin prick test (SPT). Five distinct factors were identified:(1) baseline pulmonary function measures [forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC)], (2) specific allergen sensitization by SPT, (3) self-reported allergies, (4) symptoms characteristic of rhinitis and (5) symptoms characteristic of asthma. Replication in symptomatic siblings was consistent with shared genetic and/or environmental effects, and was robust across age groups, gender, and centres. Cronbach's alpha ranged from 0.719 to 0.983 suggesting acceptable internal scale consistencies. Derived scales were correlated with serum IgE, methacholine PC(20), age and asthma severity (interrupted sleep). IgE correlated with all three atopy-related factors, the strongest with the SPT factor whereas severity only correlated with baseline lung function, and with symptoms characteristic of rhinitis and of asthma. In children and adolescents with established asthma, five distinct sets of correlated patient characteristics appear to represent important aspects of the disease. Factor scores as

Integration of transcriptomic and metabolic data reveals hub transcription factors involved in drought stress response in sunflower (Helianthus annuus L.).

PubMed

Moschen, Sebastián; Di Rienzo, Julio A; Higgins, Janet; Tohge, Takayuki; Watanabe, Mutsumi; González, Sergio; Rivarola, Máximo; García-García, Francisco; Dopazo, Joaquin; Hopp, H Esteban; Hoefgen, Rainer; Fernie, Alisdair R; Paniego, Norma; Fernández, Paula; Heinz, Ruth A

2017-07-01

By integration of transcriptional and metabolic profiles we identified pathways and hubs transcription factors regulated during drought conditions in sunflower, useful for applications in molecular and/or biotechnological breeding. Drought is one of the most important environmental stresses that effects crop productivity in many agricultural regions. Sunflower is tolerant to drought conditions but the mechanisms involved in this tolerance remain unclear at the molecular level. The aim of this study was to characterize and integrate transcriptional and metabolic pathways related to drought stress in sunflower plants, by using a system biology approach. Our results showed a delay in plant senescence with an increase in the expression level of photosynthesis related genes as well as higher levels of sugars, osmoprotectant amino acids and ionic nutrients under drought conditions. In addition, we identified transcription factors that were upregulated during drought conditions and that may act as hubs in the transcriptional network. Many of these transcription factors belong to families implicated in the drought response in model species. The integration of transcriptomic and metabolomic data in this study, together with physiological measurements, has improved our understanding of the biological responses during droughts and contributes to elucidate the molecular mechanisms involved under this environmental condition. These findings will provide useful biotechnological tools to improve stress tolerance while maintaining crop yield under restricted water availability.

The Importance of Patient-Specific Factors for Hepatic Drug Response and Toxicity

PubMed Central

Lauschke, Volker M.; Ingelman-Sundberg, Magnus

2016-01-01

Responses to drugs and pharmacological treatments differ considerably between individuals. Importantly, only 50%–75% of patients have been shown to react adequately to pharmacological interventions, whereas the others experience either a lack of efficacy or suffer from adverse events. The liver is of central importance in the metabolism of most drugs. Because of this exposed status, hepatotoxicity is amongst the most common adverse drug reactions and hepatic liabilities are the most prevalent reason for the termination of development programs of novel drug candidates. In recent years, more and more factors were unveiled that shape hepatic drug responses and thus underlie the observed inter-individual variability. In this review, we provide a comprehensive overview of different principle mechanisms of drug hepatotoxicity and illustrate how patient-specific factors, such as genetic, physiological and environmental factors, can shape drug responses. Furthermore, we highlight other parameters, such as concomitantly prescribed medications or liver diseases and how they modulate drug toxicity, pharmacokinetics and dynamics. Finally, we discuss recent progress in the field of in vitro toxicity models and evaluate their utility in reflecting patient-specific factors to study inter-individual differences in drug response and toxicity, as this understanding is necessary to pave the way for a patient-adjusted medicine. PMID:27754327

Host, vehicular and environmental factors responsible for road traffic crashes in a nigerian city: identifiable issues for road traffic injury control

PubMed Central

Adeoye, Peter Oladapo; Kadri, Dotun Musiliu; Bello, Jibril Oyekunle; Ofoegbu, Chima Kingsley Pascal; Abdur-Rahman, Lukman Olajide; Adekanye, Adedeji Olugbenga; Solagberu, Babatunde Akeeb

2014-01-01

Introduction Road traffic injury (RTI) has assumed major public health importance world-wide and the burden is heavier on the health-care infrastructure of countries in Sub-Saharan Africa. In Nigeria, RTI is the leading cause of trauma related morbidity and mortality. While there are some published epidemiological reports on RTI in the region, studies on the mechanism of causation of road traffic crashes (RTC) are not available. Methods Over a 9-month period, we prospectively captured the 571 victims of RTC presenting to a single tertiary health care center in Nigeria. Data collected include demographic data, Mechanism of causation of RTC, Injuries sustained and outcomes. Results Over three-quarters of the victims are young people and half were either traders (27.5%) or students (20%). Pedestrians, motorcycle riders and open truck occupants (people sitting at the rear loading compartment of trucks) often had fatal injuries. Analysis of collision patterns showed that lone crashes were the most frequent though car-to-motorcycle crashes caused a quarter of the deaths. Host factors (over-speeding driver, driver misjudgment, sleeping driver etc.) were responsible for four-fifths of the crashes while vehicular and environmental factors accounted for the remaining. On binary regression analysis, head injured victims had higher odds of dying than the non-head injured (Odds ratio = 6.5). Conclusion This paper elucidates the mechanisms of causation of and types of injuries sustained following RTC in Nigeria and thus provide opportunities for prevention and control of this unacceptable situation. PMID:25780490

Factors influencing the response to postal questionnaire surveys about respiratory symptoms.

PubMed

Hazell, Michelle L; Morris, Julie A; Linehan, Mary F; Frank, Peter I; Frank, Timothy L

2009-09-01

Response rates to postal questionnaires have been falling in recent years. To examine factors affecting the response to five postal respiratory questionnaire surveys. Cross sectional study. General practice. Five surveys were conducted in all adults registered with two UK general practices using an ECRHQ-based questionnaire, with two reminders at 4-week intervals. Response rates declined over time (1993 - 71.2%; 1995 - 70.5%; 1999 - 65.5%; 2001 - 65.3%; 2004 - 46.9%). Age and gender of non-responders were available for 2001 and 2004: responders were older (mean 48.8 years vs 37.6, p<0.001; 50.5 vs 38.8, p<0.001) and more likely to be female (54.9% vs 44.9%, p<0.001; 55.3% vs 48.5%, p<0.001). The response rate was increased by 18% (2004) and 23% (2001) by the use of two reminders. Early responders were older and more likely to be females, but were less likely to smoke than late responders after reminders. There was no important association between respiratory symptoms and associated feature prevalence and stage of response. Declining response rates may represent reduced motivation and reluctance to share personal information. Qualitative exploration of late/non-response could help reduce bias when planning and analysing such surveys. The use of two reminders is an important factor in improving response.

Identifying gnostic predictors of the vaccine response

PubMed Central

Haining, W. Nicholas; Pulendran, Bali

2012-01-01

Molecular predictors of the response to vaccination could transform vaccine development. They would allow larger numbers of vaccine candidates to be rapidly screened, shortening the development time for new vaccines. Gene-expression based predictors of vaccine response have shown early promise. However, a limitation of gene-expression based predictors is that they often fail to reveal the mechanistic basis for their ability to classify response. Linking predictive signatures to the function of their component genes would advance basic understanding of vaccine immunity and also improve the robustness of outcome classification. New analytic tools now allow more biological meaning to be extracted from predictive signatures. Functional genomic approaches to perturb gene expression in mammalian cells permit the function of predictive genes to be surveyed in highly parallel experiments. The challenge for vaccinologists is therefore to use these tools to embed mechanistic insights into predictors of vaccine response. PMID:22633886

Biogastronomy: Factors that determine the biological response to meal ingestion.

PubMed

Pribic, T; Azpiroz, F

2018-02-02

The biological response to a meal includes physiological changes, primarily related to the digestive process, and a sensory experience, involving sensations related to the homeostatic control of food consumption, eg, satiety and fullness, with a hedonic dimension, ie associated with changes in digestive well-being and mood. The responses to a meal include a series of events before, during and after ingestion. While much attention has been paid to the events before and during ingestion, relatively little is known about the postprandial sensations, which are key to the gastronomical experience. The aim of this narrative review is to provide a comprehensive overview and to define the framework to investigate the factors that determine the postprandial experience. Based on a series of proof-of-concept studies and related information, we propose that the biological responses to a meal depend on the characteristics of the meal, primarily its palatability and composition, and the responsiveness of the guest, which may be influenced by multiple previous and concurrent conditioning factors. This information provides the scientific backbone to the development of personalized gastronomy. © 2018 John Wiley & Sons Ltd.

Clinical, histological, immunohistochemical and genetic factors associated with measurable response of high-risk canine mast cell tumours to tyrosine kinase inhibitors

PubMed Central

Horta, Rodrigo dos Santos; Giuliano, Antonio; Lavalle, Gleidice Eunice; Costa, Mariana de Pádua; de Araújo, Roberto Baracat; Constantino-Casas, Fernando; Dobson, Jane Margaret

2018-01-01

The aim of the present prospective-retrospective study was to evaluate the response of high-risk canine mast cell tumours (MCTs) to tyrosine kinase inhibitors (TKIs) and to correlate this with prognostic factors. A total of 24 dogs presented with macroscopic cutaneous MCTs at disease stage II or III, and therefore, at high-risk of associated mortality, were included in the study and treated with masitinib (n=20) or toceranib (n=4). A total of 12/24 dogs achieved an objective response and the overall survival (OS) for all subjects was 113 days. Dogs responding to treatment had a significant increase in OS compared to non-responders (146.5 days vs. 47 days, P=0.02). Internal tandem duplications in exon 11 of the c-kit gene were identified in 6/24 cases. Ki67, KIT immunolabelling and c-kit mutation did not provide information regarding prognosis or prediction of response to TKIs in this population. Initial response to TKIs appears to be the most reliable prognostic factor for survival duration. PMID:29387214

Identifying gnostic predictors of the vaccine response.

PubMed

Haining, W Nicholas; Pulendran, Bali

2012-06-01

Molecular predictors of the response to vaccination could transform vaccine development. They would allow larger numbers of vaccine candidates to be rapidly screened, shortening the development time for new vaccines. Gene-expression based predictors of vaccine response have shown early promise. However, a limitation of gene-expression based predictors is that they often fail to reveal the mechanistic basis of their ability to classify response. Linking predictive signatures to the function of their component genes would advance basic understanding of vaccine immunity and also improve the robustness of vaccine prediction. New analytic tools now allow more biological meaning to be extracted from predictive signatures. Functional genomic approaches to perturb gene expression in mammalian cells permit the function of predictive genes to be surveyed in highly parallel experiments. The challenge for vaccinologists is therefore to use these tools to embed mechanistic insights into predictors of vaccine response. Copyright © 2012 Elsevier Ltd. All rights reserved.

Systems biology approach identifies the kinase Csnk1a1 as a regulator of the DNA damage response in embryonic stem cells.

PubMed

Carreras Puigvert, Jordi; von Stechow, Louise; Siddappa, Ramakrishnaiah; Pines, Alex; Bahjat, Mahnoush; Haazen, Lizette C J M; Olsen, Jesper V; Vrieling, Harry; Meerman, John H N; Mullenders, Leon H F; van de Water, Bob; Danen, Erik H J

2013-01-22

In pluripotent stem cells, DNA damage triggers loss of pluripotency and apoptosis as a safeguard to exclude damaged DNA from the lineage. An intricate DNA damage response (DDR) signaling network ensures that the response is proportional to the severity of the damage. We combined an RNA interference screen targeting all kinases, phosphatases, and transcription factors with global transcriptomics and phosphoproteomics to map the DDR in mouse embryonic stem cells treated with the DNA cross-linker cisplatin. Networks derived from canonical pathways shared in all three data sets were implicated in DNA damage repair, cell cycle and survival, and differentiation. Experimental probing of these networks identified a mode of DNA damage-induced Wnt signaling that limited apoptosis. Silencing or deleting the p53 gene demonstrated that genotoxic stress elicited Wnt signaling in a p53-independent manner. Instead, this response occurred through reduced abundance of Csnk1a1 (CK1α), a kinase that inhibits β-catenin. Together, our findings reveal a balance between p53-mediated elimination of stem cells (through loss of pluripotency and apoptosis) and Wnt signaling that attenuates this response to tune the outcome of the DDR.

Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses

PubMed Central

Luo, Jie; Xu, Pei; Cao, Peijian; Wan, Hongjian; Lv, Xiaonan; Xu, Shengchun; Wang, Gangjun; Cook, Melloni N.; Jones, Byron C.; Lu, Lu; Wang, Xusheng

2018-01-01

Although the link between stress and alcohol is well recognized, the underlying mechanisms of how they interplay at the molecular level remain unclear. The purpose of this study is to identify molecular networks underlying the effects of alcohol and stress responses, as well as their interaction on anxiety behaviors in the hippocampus of mice using a systems genetics approach. Here, we applied a gene co-expression network approach to transcriptomes of 41 BXD mouse strains under four conditions: stress, alcohol, stress-induced alcohol and control. The co-expression analysis identified 14 modules and characterized four expression patterns across the four conditions. The four expression patterns include up-regulation in no restraint stress and given an ethanol injection (NOE) but restoration in restraint stress followed by an ethanol injection (RSE; pattern 1), down-regulation in NOE but rescue in RSE (pattern 2), up-regulation in both restraint stress followed by a saline injection (RSS) and NOE, and further amplification in RSE (pattern 3), and up-regulation in RSS but reduction in both NOE and RSE (pattern 4). We further identified four functional subnetworks by superimposing protein-protein interactions (PPIs) to the 14 co-expression modules, including γ-aminobutyric acid receptor (GABA) signaling, glutamate signaling, neuropeptide signaling, cAMP-dependent signaling. We further performed module specificity analysis to identify modules that are specific to stress, alcohol, or stress-induced alcohol responses. Finally, we conducted causality analysis to link genetic variation to these identified modules, and anxiety behaviors after stress and alcohol treatments. This study underscores the importance of integrative analysis and offers new insights into the molecular networks underlying stress and alcohol responses. PMID:29674951

Design Factors Affecting the Reaction Time for Identifying Toilet Signs: A Preliminary Study.

PubMed

Chen, Yi-Lang; Sie, Cai-Cin

2016-04-01

This study focused on the manner in which design factors affect the reaction time for identifying toilet signs. Taiwanese university students and staff members (50 men, 50 women; M age = 23.5 year, SD = 5.7) participated in the study. The 36 toilet signs were modified on three factors (six presenting styles, two figure-ground exchanges, and three colors), and the reaction time data of all participants were collected when the signs were presented in a simulation onscreen. Participants were quickest when reading Chinese text, followed by graphics and English texts. The findings also showed that men and women had different reaction times across various design combinations. These findings can serve as a reference for practically designing toilet signs, since design factors can lead to difficulties with comprehension based on reaction time measurements. © The Author(s) 2016.

Factors influencing speech and language outcomes of children with early identified severe/profound hearing loss: Clinician-identified facilitators and barriers.

PubMed

Fulcher, Anne Nivelles; Purcell, Alison; Baker, Elise; Munro, Natalie

2015-06-01

Early identification of severe/profound childhood hearing loss (HL) gives these children access to hearing devices and early intervention to facilitate improved speech and language outcomes. Predicting which infants will go on to achieve such outcomes remains difficult. This study describes clinician identified malleable and non-malleable factors that may influence speech and language outcomes for children with severe/profound HL. Semi-structured interviews were conducted with six experienced auditory verbal clinicians. A collective case study design was implemented. The interviews were transcribed and coded into themes using constant comparative analysis. Clinicians identified that, for children with severe/profound HL, early identification, early amplification and commencing auditory-verbal intervention under 6 months of age may facilitate child progress. Possible barriers were living in rural/remote areas, the clinicians' lack of experience and confidence in providing intervention for infants under age 6-months and belonging to a family with a culturally and linguistically diverse (CALD) background. The results indicate that multiple factors need to be considered by clinicians working with children with HL and their families to determine how each child functions within their own environment and personal contexts, consistent with the International Classification of Functioning, Disability and Health (ICF) framework. Such an approach is likely to empower clinicians to carefully balance potential barriers to, and facilitators of, optimal speech and language outcomes for all children with HL.

A heteroscedastic generalized linear model with a non-normal speed factor for responses and response times.

PubMed

Molenaar, Dylan; Bolsinova, Maria

2017-05-01

In generalized linear modelling of responses and response times, the observed response time variables are commonly transformed to make their distribution approximately normal. A normal distribution for the transformed response times is desirable as it justifies the linearity and homoscedasticity assumptions in the underlying linear model. Past research has, however, shown that the transformed response times are not always normal. Models have been developed to accommodate this violation. In the present study, we propose a modelling approach for responses and response times to test and model non-normality in the transformed response times. Most importantly, we distinguish between non-normality due to heteroscedastic residual variances, and non-normality due to a skewed speed factor. In a simulation study, we establish parameter recovery and the power to separate both effects. In addition, we apply the model to a real data set. © 2017 The Authors. British Journal of Mathematical and Statistical Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

Dyadic confirmatory factor analysis of the inflammatory bowel disease family responsibility questionnaire.

PubMed

Greenley, Rachel Neff; Reed-Knight, Bonney; Blount, Ronald L; Wilson, Helen W

2013-09-01

Evaluate the factor structure of youth and maternal involvement ratings on the Inflammatory Bowel Disease Family Responsibility Questionnaire, a measure of family allocation of condition management responsibilities in pediatric inflammatory bowel disease. Participants included 251 youth aged 11-18 years with inflammatory bowel disease and their mothers. Item-level descriptive analyses, subscale internal consistency estimates, and confirmatory factor analyses of youth and maternal involvement were conducted using a dyadic data-analytic approach. Results supported the validity of 4 conceptually derived subscales including general health maintenance, social aspects, condition management tasks, and nutrition domains. Additionally, results indicated adequate support for the factor structure of a 21-item youth involvement measure and strong support for a 16-item maternal involvement measure. Additional empirical support for the validity of the Inflammatory Bowel Disease Family Responsibility Questionnaire was provided. Future research to replicate current findings and to examine the measure's clinical utility is warranted.

Elevated-CO2 Response of Stomata and Its Dependence on Environmental Factors

PubMed Central

Xu, Zhenzhu; Jiang, Yanling; Jia, Bingrui; Zhou, Guangsheng

2016-01-01

Stomata control the flow of gases between plants and the atmosphere. This review is centered on stomatal responses to elevated CO2 concentration and considers other key environmental factors and underlying mechanisms at multiple levels. First, an outline of general responses in stomatal conductance under elevated CO2 is presented. Second, stomatal density response, its development, and the trade-off with leaf growth under elevated CO2 conditions are depicted. Third, the molecular mechanism regulating guard cell movement at elevated CO2 is suggested. Finally, the interactive effects of elevated CO2 with other factors critical to stomatal behavior are reviewed. It may be useful to better understand how stomata respond to elevated CO2 levels while considering other key environmental factors and mechanisms, including molecular mechanism, biochemical processes, and ecophysiological regulation. This understanding may provide profound new insights into how plants cope with climate change. PMID:27242858

The RNA Polymerase-Associated Factor 1 Complex Is Required for Plant Touch Responses

PubMed Central

Jensen, Gregory S.; Fal, Kateryna; Hamant, Olivier

2017-01-01

Abstract Thigmomorphogenesis is a stereotypical developmental alteration in the plant body plan that can be induced by repeatedly touching plant organs. To unravel how plants sense and record multiple touch stimuli we performed a novel forward genetic screen based on the development of a shorter stem in response to repetitive touch. The touch insensitive (ths1) mutant identified in this screen is defective in some aspects of shoot and root thigmomorphogenesis. The ths1 mutant is an intermediate loss-of-function allele of VERNALIZATION INDEPENDENCE 3 (VIP3), a previously characterized gene whose product is part of the RNA polymerase II-associated factor 1 (Paf1) complex. The Paf1 complex is found in yeast, plants and animals, and has been implicated in histone modification and RNA processing. Several components of the Paf1 complex are required for reduced stem height in response to touch and normal root slanting and coiling responses. Global levels of histone H3K36 trimethylation are reduced in VIP3 mutants. In addition, THS1/VIP3 is required for wild type histone H3K36 trimethylation at the TOUCH3 (TCH3) and TOUCH4 (TCH4) loci and for rapid touch-induced upregulation of TCH3 and TCH4 transcripts. Thus, an evolutionarily conserved chromatin-modifying complex is required for both short- and long-term responses to mechanical stimulation, providing insight into how plants record mechanical signals for thigmomorphogenesis. PMID:28204553

Identifying risk factors for victimization among male prisoners in Taiwan.

PubMed

Kuo, Shih-Ya; Cuvelier, Steven J; Huang, Yung-Shun

2014-02-01

This study identified risk factors for prison victimization in Taiwan with an application of Western literature and assessed the extent of its applicability in an Eastern context. The sample was drawn from four male prisons located in Northern, Central, Southern, and Eastern Taiwan; a total of 1,181 valid surveys were collected. The results generally support the major findings of the extant Western studies. Crowding, however, was not significantly associated with the risk of victimization in any of the statistical models, which might be related to the different experiences and living conditions in the free community between Taiwanese and American inmates. This study generated clear policy implications, which may reduce prison victimization and engender a greater sense of well-being in the prison environment.

MONKEY: Identifying conserved transcription-factor binding sitesin multiple alignments using a binding site-specific evolutionarymodel

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

Moses, Alan M.; Chiang, Derek Y.; Pollard, Daniel A.

2004-10-28

We introduce a method (MONKEY) to identify conserved transcription-factor binding sites in multispecies alignments. MONKEY employs probabilistic models of factor specificity and binding site evolution, on which basis we compute the likelihood that putative sites are conserved and assign statistical significance to each hit. Using genomes from the genus Saccharomyces, we illustrate how the significance of real sites increases with evolutionary distance and explore the relationship between conservation and function.

Use of RADs to identify canidate genes for response to crowding stress in rainbow trout

USDA-ARS?s Scientific Manuscript database

Fish under intensive rearing conditions experience various stressors which have negative impacts on survival, growth, reproduction and fillet quality. Identifying and characterizing the molecular mechanisms underlying stress responses will facilitate the development of strategies that aim to improve...

Phases of female sexual response cycle among Malaysian women with infertility: a factor analysis study.

PubMed

Seen Heng, Yeoh; Sidi, Hatta; Nik Jaafar, Nik Ruzyanei; Razali, Rosdinom; Ram, Hari

2013-04-01

This cross-sectional study aimed to determine the construct of the phases of the female sexual response cycle (SRC) among women attending an infertility clinic in a Malaysian tertiary center. The sexual response phases were measured with a validated Malay version of the Female Sexual Function Index (FSFI). The correlation structure of the items of the SRC phases (i.e. desire, arousal, orgasm, satisfaction and pain) was determined using principal component analysis (PCA), with varimax rotation method. The number of factors obtained was decided using Kaiser's criteria. A total of 150 married women with a mean age of 32 years participated in this study. Factor loadings using PCA with varimax rotation divided the sexual domains into three components. The first construct comprised sexual arousal, lubrication and pain (suggesting a mechanical component). The second construct were orgasm and sexual satisfaction (suggesting a physical achievement). Sexual desire, suggesting a psychological component, stood on its own as the third. The findings suggest that three constructs could be identified and in favor of the Basson model (a non-linear concept of SRC) for Malaysian women's sexual functioning. Understanding this would help clinicians to strategize the treatment approach of sexual dysfunction in women with infertility. Copyright © 2013 Wiley Publishing Asia Pty Ltd.

Wild soybean roots depend on specific transcription factors and oxidation reduction related genesin response to alkaline stress.

PubMed

DuanMu, Huizi; Wang, Yang; Bai, Xi; Cheng, Shufei; Deyholos, Michael K; Wong, Gane Ka-Shu; Li, Dan; Zhu, Dan; Li, Ran; Yu, Yang; Cao, Lei; Chen, Chao; Zhu, Yanming

2015-11-01

Soil alkalinity is an important environmental problem limiting agricultural productivity. Wild soybean (Glycine soja) shows strong alkaline stress tolerance, so it is an ideal plant candidate for studying the molecular mechanisms of alkaline tolerance and identifying alkaline stress-responsive genes. However, limited information is available about G. soja responses to alkaline stress on a genomic scale. Therefore, in the present study, we used RNA sequencing to compare transcript profiles of G. soja root responses to sodium bicarbonate (NaHCO3) at six time points, and a total of 68,138,478 pairs of clean reads were obtained using the Illumina GAIIX. Expression patterns of 46,404 G. soja genes were profiled in all six samples based on RNA-seq data using Cufflinks software. Then, t12 transcription factors from MYB, WRKY, NAC, bZIP, C2H2, HB, and TIFY families and 12 oxidation reduction related genes were chosen and verified to be induced in response to alkaline stress by using quantitative real-time polymerase chain reaction (qRT-PCR). The GO functional annotation analysis showed that besides "transcriptional regulation" and "oxidation reduction," these genes were involved in a variety of processes, such as "binding" and "response to stress." This is the first comprehensive transcriptome profiling analysis of wild soybean root under alkaline stress by RNA sequencing. Our results highlight changes in the gene expression patterns and identify a set of genes induced by NaHCO3 stress. These findings provide a base for the global analyses of G. soja alkaline stress tolerance mechanisms.

Identifying crash contributory factors at urban roundabouts and using association rules to explore their relationships to different crash types.

PubMed

Montella, Alfonso

2011-07-01

The use of roundabouts improves intersection safety by eliminating or altering conflict types, reducing crash severity, and causing drivers to reduce speeds. However, roundabout performances can degrade if precautions are not taken during either the design or the operation phase. Therefore, additional information on the safety of the roundabouts is extremely helpful for planners and designers in identifying existing deficiencies and in refining the design criteria currently being used. The aim of the paper was to investigate the crash contributory factors in 15 urban roundabouts located in Italy and to study the interdependences between these factors. The crash data refer to the period 2003-2008. The identification of the crash contributory factors was based on site inspections and rigorous analyses performed by a team of specialists with a relevant road safety engineering background. Each roundabout was inspected once every year from 2004 to 2009, both in daytime and in nighttime. Overall, 62 different contributory factors and 2156 total contributory factors were identified. In 51 crashes, a single contributory factor was found, whereas in the other 223 crashes, a combination of contributory factors was identified. Given the large amount of data, the interdependences between the contributory factors and between the contributory factors and the different crash types were explored by an association discovery. Association discovery is the identification of sets of items (i.e., crash contributory factors and crash types in our study) that occur together in a given event (i.e., a crash in our study). The rules were filtered by support, confidence, and lift. As a result, 112 association rules were discovered. Overall, numerous contributory factors related to the road and environment deficiencies but not related to the road user or to the vehicle were identified. The most important factors related to geometric design were the radius of deflection and the deviation angle

Risk factors identified for certain lymphoma subtypes

Cancer.gov

In a large international collaborative analysis of risk factors for non-Hodgkin lymphoma (NHL), scientists were able to quantify risk associated with medical history, lifestyle factors, family history of blood or lymph-borne cancers, and occupation for 11

Different responses of influenza epidemic to weather factors among Shanghai, Hong Kong, and British Columbia.

PubMed

Wang, Xi-Ling; Yang, Lin; He, Dai-Hai; Chiu, Alice Py; Chan, Kwok-Hung; Chan, King-Pan; Zhou, Maigeng; Wong, Chit-Ming; Guo, Qing; Hu, Wenbiao

2017-06-01

Weather factors have long been considered as key sources for regional heterogeneity of influenza seasonal patterns. As influenza peaks coincide with both high and low temperature in subtropical cities, weather factors may nonlinearly or interactively affect influenza activity. This study aims to assess the nonlinear and interactive effects of weather factors with influenza activity and compare the responses of influenza epidemic to weather factors in two subtropical regions of southern China (Shanghai and Hong Kong) and one temperate province of Canada (British Columbia). Weekly data on influenza activity and weather factors (i.e., mean temperature and relative humidity (RH)) were obtained from pertinent government departments for the three regions. Absolute humidity (AH) was measured by vapor pressure (VP), which could be converted from temperature and RH. Generalized additive models were used to assess the exposure-response relationship between weather factors and influenza virus activity. Interactions of weather factors were further assessed by bivariate response models and stratification analyses. The exposure-response curves of temperature and VP, but not RH, were consistent among three regions/cities. Bivariate response model revealed a significant interactive effect between temperature (or VP) and RH (P < 0.05). Influenza peaked at low temperature or high temperature with high RH. Temperature and VP are important weather factors in developing a universal model to explain seasonal outbreaks of influenza. However, further research is needed to assess the association between weather factors and influenza activity in a wider context of social and environmental conditions.

Comparison of genomics and functional imaging from canine sarcomas treated with thermoradiotherapy predicts therapeutic response and identifies combination therapeutics

PubMed Central

Chi, Jen-Tsan; Thrall, Donald E.; Jiang, Chen; Snyder, Stacey; Fels, Diane; Landon, Chelsea; McCall, Linda; Lan, Lan; Hauck, Marlene; MacFall, James R.; Viglianti, Benjamin L.; Dewhirst, Mark W.

2011-01-01

Purpose While hyperthermia is an effective adjuvant treatment to radiotherapy, we don’t completely understand the nature of the response heterogeneity. Experimental Design We performed gene expression analysis of 22 spontaneous canine sarcomas before and after the first hyperthermia treatment administered as an adjuvant to radiotherapy. In parallel, diffusion weighted MRI (DWI) was done prior to the treatment course and at the end of therapy. Results From the integrative analysis of gene expression and DWI, we identified significant correlation between tumor responses with genes involved in VEGF signaling, telomerase, DNA repair and inflammation. The treatment-induced changes in gene expression identified two distinct tumor subtypes with significant differences in their gene expression and treatment response, as defined by changes in DWI. The two tumor subtypes could also be readily identified by pre-treatment gene expression. The tumor subtypes, with stronger expression response and DWI increase, had higher levels of hsp70, POT1 and centrosomal proteins and lower levels of CD31, vWF and transferrin. Such differential gene expression between the two subtypes was used to interrogate connectivity map and identify linkages to an HSP90 inhibitor, geldanamycin. We further validated the ability of geldanamycin to enhance cell killing of human tumor cells with hyperthermia and radiotherapy in clonogenic assays. Conclusions To our knowledge, this is one of the first successful attempts to link changes in gene expression and functional imaging to understand the response heterogeneity and identify compounds enhancing thermoradiotherapy. This study also demonstrates the value of canine tumors to provide information generalizable to human tumors. PMID:21292819

Bean Metal-Responsive Element-Binding Transcription Factor Confers Cadmium Resistance in Tobacco1

PubMed Central

Sun, Na; Liu, Meng; Zhang, Wentao; Yang, Wanning; Bei, Xiujuan; Ma, Hui; Qiao, Fan; Qi, Xiaoting

2015-01-01

Cadmium (Cd) is highly toxic to plants. Modulation of Cd-responsive transcription is an important way for Cd detoxification in plants. Metal-responsive element (MRE) is originally described in animal metallothionein genes. Although functional MREs also exist in Cd-regulated plant genes, specific transcription factors that bind MRE to regulate Cd tolerance have not been identified. Previously, we showed that Cd-inducible bean (Phaseolus vulgaris) stress-related gene2 (PvSR2) produces a short (S) PvSR2 transcript (S-PvSR2) driven by an intronic promoter. Here, we demonstrate that S-PvSR2 encodes a bean MRE-binding transcription factor1 (PvMTF-1) that confers Cd tolerance in tobacco (Nicotiana tabacum). PvMTF-1 expression was up-regulated by Cd at the levels of RNA and protein. Importantly, expression of PvMTF-1 in tobacco enhanced Cd tolerance, indicating its role in regulating Cd resistance in planta. This was achieved through direct regulation of a feedback-insensitive Anthranilate Synthase α-2 chain gene (ASA2), which catalyzes the first step for tryptophan biosynthesis. In vitro and in vivo DNA-protein interaction studies further revealed that PvMTF-1 directly binds to the MRE in the ASA2 promoter, and this binding depends on the zinc finger-like motif of PvMTF-1. Through modulating ASA2 up-regulation by Cd, PvMTF-1 increased free tryptophan level and subsequently reduced Cd accumulation, thereby enhancing Cd tolerance of transgenic tobacco plants. Consistent with this observation, tobacco transiently overexpressing ASA2 also exhibited increased tolerance to Cd. We conclude that PvMTF-1 is a zinc finger-like transcription factor that links MRE to Cd resistance in transgenic tobacco through activation of tryptophan biosynthesis. PMID:25624396

Identifying functional groups for response to disturbance in an abandoned pasture

NASA Astrophysics Data System (ADS)

Lavorel, Sandra; Touzard, Blaise; Lebreton, Jean-Dominique; Clément, Bernard

1998-06-01

In an abandoned pasture in Brittany, we compared artificial small-scale disturbances to natural disturbances by wild boar and undisturbed vegetation. We developed a multivariate statistical approach which analyses how species biological attributes explain the response of community composition to disturbances. This technique, which reconciles the inductive and deductive approaches for functional classifications, identifies groups of species with similar responses to disturbance and characterizes their biological profiles. After 5 months of recolonization, artificial disturbances had a greater species richness than undisturbed vegetation as a result of recruitment of new species without the exclusion of pre-existing matrix species. Species morphology, described by canopy structure, canopy height and lateral spread, explained a large part (16 %) of community response to disturbance. Regeneration strategies, described by life history, seed mass, dispersal agent, dormancy and the existence of vegetative multiplication, explained a smaller part of community response to disturbance (8 %). Artificial disturbances were characterized by therophyte and compact rosettes with moderately dormant seeds, including a number of Asteraceae and other early successional species. Natural disturbances were colonized by leafy guerrilla species without seed dormancy. Few species were tightly related to undisturbed vegetation and were essentially grasses with a phalanx rosette morphology. The functional classification obtained is consistent with the classification of the community into fugitives, regenerators and persistors. These groups are structured according to Grubb's model for temperate grasslands, with regenerators and persistors in the matrix and fugitives taking advantage of gaps open by small-scale disturbances. The conjunction of functional diversity and species diversity within functional groups is the key to resilience to disturbance, an important ecosystem function.

Circulating RNA transcripts identify therapeutic response in cystic fibrosis lung disease.

PubMed

Saavedra, Milene T; Hughes, Grant J; Sanders, Linda A; Carr, Michelle; Rodman, David M; Coldren, Christopher D; Geraci, Mark W; Sagel, Scott D; Accurso, Frank J; West, James; Nick, Jerry A

2008-11-01

Circulating leukocyte RNA transcripts are systemic markers of inflammation, which have not been studied in cystic fibrosis (CF) lung disease. Although the standard assessment of pulmonary treatment response is FEV(1), a measure of airflow limitation, the lack of systemic markers to reflect changes in lung inflammation critically limits the testing of proposed therapeutics. We sought to prospectively identify and validate peripheral blood leukocyte genes that could mark resolution of pulmonary infection and inflammation using a model by which RNA transcripts could increase the predictive value of spirometry. Peripheral blood mononuclear cells were isolated from 10 patients with CF and acute pulmonary exacerbations before and after therapy. RNA expression profiling revealed that 10 genes significantly changed with treatment when compared with matched non-CF and control subjects with stable CF to establish baseline transcript abundance. Peripheral blood mononuclear cell RNA transcripts were prospectively validated, using real-time polymerase chain reaction amplification, in an independent cohort of acutely ill patients with CF (n = 14). Patients who responded to therapy were analyzed using general estimating equations and multiple logistic regression, such that changes in FEV(1)% predicted were regressed with transcript changes. Three genes, CD64, ADAM9, and CD36, were significant and independent predictors of a therapeutic response beyond that of FEV(1) alone (P < 0.05). In both cohorts, receiver operating characteristic analysis revealed greater accuracy when genes were combined with FEV(1). Circulating mononuclear cell transcripts characterize a response to the treatment of pulmonary exacerbations. Even in small patient cohorts, changes in gene expression in conjunction with FEV(1) may enhance current outcomes measures for treatment response.

Factor Responsible for Examination Malpractices as Expressed by Undergraduates of Osun State University, Nigeria

ERIC Educational Resources Information Center

Yusuf; Adeoti, Florence; Olufunke, Yinusa Rasheedat; Ruth, Bamgbose Oluwayemisi

2015-01-01

The study investigated perception of undergraduates on factors responsible for examination malpractices. The study is a descriptive study; a sample of two hundred (200) undergraduates formed the participants for the study. A questionnaire titled: "Factor responsible for examination malpractices was used for data collection. Data collected…

Identifying Factors Related to Food Agency: Cooking Habits in the Spanish Adult Population-A Cross-Sectional Study.

PubMed

García-González, Ángela; Achón, María; Alonso-Aperte, Elena; Varela-Moreiras, Gregorio

2018-02-15

This study focuses on understanding factors that influence food agency in the Spanish population, specifically with regard to cooking habits, knowledge, and determinants and their possible relationship with body weight. A cross-sectional telephone survey was conducted. Individuals were asked about their cooking responsibilities, how they learned to cook, factors that affect their food choices, and their preferred cooking techniques. Anthropometric data were also recorded. Participants were randomly selected, and we finally had 2026 respondents aged ≥18 years (60% women, 40% men). A total of 90.5% of participants stated that they had cooking skills. Women were mainly responsible for cooking tasks ( p < 0.05) at all ages. A significantly higher proportion of people under 50 years self-reported that they were "able to cook" in comparison with groups over 50 years. Regardless of age, most participants learned to cook either by practice (43.3%) or from a family member (42.2%). Men tended to be more autodidactic, whereas women reported learning from family. No relation was found between weight status and the evaluated factors investigated. In conclusion, women bear the responsibility for the entire cooking process in families, indicating a gender gap in the involvement of men in cooking responsibilities and competence. More research is needed to assess the influence of cooking knowledge on obesity prevention.

Identifying Factors Related to Food Agency: Cooking Habits in the Spanish Adult Population—A Cross-Sectional Study

PubMed Central

García-González, Ángela; Varela-Moreiras, Gregorio

2018-01-01

This study focuses on understanding factors that influence food agency in the Spanish population, specifically with regard to cooking habits, knowledge, and determinants and their possible relationship with body weight. A cross-sectional telephone survey was conducted. Individuals were asked about their cooking responsibilities, how they learned to cook, factors that affect their food choices, and their preferred cooking techniques. Anthropometric data were also recorded. Participants were randomly selected, and we finally had 2026 respondents aged ≥18 years (60% women, 40% men). A total of 90.5% of participants stated that they had cooking skills. Women were mainly responsible for cooking tasks (p < 0.05) at all ages. A significantly higher proportion of people under 50 years self-reported that they were “able to cook” in comparison with groups over 50 years. Regardless of age, most participants learned to cook either by practice (43.3%) or from a family member (42.2%). Men tended to be more autodidactic, whereas women reported learning from family. No relation was found between weight status and the evaluated factors investigated. In conclusion, women bear the responsibility for the entire cooking process in families, indicating a gender gap in the involvement of men in cooking responsibilities and competence. More research is needed to assess the influence of cooking knowledge on obesity prevention. PMID:29462887

Identifying Some Factors That Might Predispose Drug Abuse among Learners in a South African Township School

ERIC Educational Resources Information Center

Grobler, R.; Khatite, M.

2012-01-01

This study inquires into some of the factors that might predispose the use and abuse of drugs among secondary school learners in a township school. The objective of this research is to identify these factors and to offer a few suggestions on how the abuse may be prevented. A quantitative research strategy is used and a document analysis technique…

[Predictive factors of virological response in chronically HCV infected].

PubMed

Lapiński, Tadeusz Wojciech; Flisiak, Robert

2012-09-01

Research on new antivirals drugs applied in the treatment of chronically HCV infected indicate that even the most perfect therapeutic molecules do not guarantee 100% efficacy. Since the beginning of the history of HCV infection treatment clinicians looked for predictors of treatment efficacy. Numerous studies confirm the high probability of cure in patients who cleared HCVinfectional 4 and 12 weeks of therapy. However despite of viral factors, recent research demonstrated predictive role of some host dependent factors. The most important role seems to play genetic factors including polymorphism rs12979860, as well as chemokins including first of all CXCL10 (IP-10). Very interesting seems to be also results of studies on association between vitamine D concentration and treatment efficacy. However in the future the most important predictive factor remain probably early on-treatment viral response.

The auxin response factor gene family in banana: genome-wide identification and expression analyses during development, ripening, and abiotic stress

PubMed Central

Hu, Wei; Zuo, Jiao; Hou, Xiaowan; Yan, Yan; Wei, Yunxie; Liu, Juhua; Li, Meiying; Xu, Biyu; Jin, Zhiqiang

2015-01-01

Auxin signaling regulates various auxin-responsive genes via two types of transcriptional regulators, Auxin Response Factors (ARF) and Aux/IAA. ARF transcription factors act as critical components of auxin signaling that play important roles in modulating various biological processes. However, limited information about this gene family in fruit crops is currently available. Herein, 47 ARF genes were identified in banana based on its genome sequence. Phylogenetic analysis of the ARFs from banana, rice, and Arabidopsis suggested that the ARFs could be divided into four subgroups, among which most ARFs from the banana showed a closer relationship with those from rice than those from Arabidopsis. Conserved motif analysis showed that all identified MaARFs had typical DNA-binding and ARF domains, but 12 members lacked the dimerization domain. Gene structure analysis showed that the number of exons in MaARF genes ranged from 5 to 21, suggesting large variation amongst banana ARF genes. The comprehensive expression profiles of MaARF genes yielded useful information about their involvement in diverse tissues, different stages of fruit development and ripening, and responses to abiotic stresses in different varieties. Interaction networks and co-expression assays indicated the strong transcriptional response of banana ARFs and ARF-mediated networks in early fruit development for different varieties. Our systematic analysis of MaARFs revealed robust tissue-specific, development-dependent, and abiotic stress-responsive candidate MaARF genes for further functional assays in planta. These findings could lead to potential applications in the genetic improvement of banana cultivars, and yield new insights into the complexity of the control of MaARF gene expression at the transcriptional level. Finally, they support the hypothesis that ARFs are a crucial component of the auxin signaling pathway, which regulates a wide range of physiological processes. PMID:26442055

Capture of microRNA-bound mRNAs identifies the tumor suppressor miR-34a as a regulator of growth factor signaling.

PubMed

Lal, Ashish; Thomas, Marshall P; Altschuler, Gabriel; Navarro, Francisco; O'Day, Elizabeth; Li, Xiao Ling; Concepcion, Carla; Han, Yoon-Chi; Thiery, Jerome; Rajani, Danielle K; Deutsch, Aaron; Hofmann, Oliver; Ventura, Andrea; Hide, Winston; Lieberman, Judy

2011-11-01

A simple biochemical method to isolate mRNAs pulled down with a transfected, biotinylated microRNA was used to identify direct target genes of miR-34a, a tumor suppressor gene. The method reidentified most of the known miR-34a regulated genes expressed in K562 and HCT116 cancer cell lines. Transcripts for 982 genes were enriched in the pull-down with miR-34a in both cell lines. Despite this large number, validation experiments suggested that ~90% of the genes identified in both cell lines can be directly regulated by miR-34a. Thus miR-34a is capable of regulating hundreds of genes. The transcripts pulled down with miR-34a were highly enriched for their roles in growth factor signaling and cell cycle progression. These genes form a dense network of interacting gene products that regulate multiple signal transduction pathways that orchestrate the proliferative response to external growth stimuli. Multiple candidate miR-34a-regulated genes participate in RAS-RAF-MAPK signaling. Ectopic miR-34a expression reduced basal ERK and AKT phosphorylation and enhanced sensitivity to serum growth factor withdrawal, while cells genetically deficient in miR-34a were less sensitive. Fourteen new direct targets of miR-34a were experimentally validated, including genes that participate in growth factor signaling (ARAF and PIK3R2) as well as genes that regulate cell cycle progression at various phases of the cell cycle (cyclins D3 and G2, MCM2 and MCM5, PLK1 and SMAD4). Thus miR-34a tempers the proliferative and pro-survival effect of growth factor stimulation by interfering with growth factor signal transduction and downstream pathways required for cell division.

Individual differences in maternal response to immune challenge predict offspring behavior: Contribution of environmental factors

PubMed Central

Bronson, Stefanie L.; Ahlbrand, Rebecca; Horn, Paul S.; Kern, Joseph R.; Richtand, Neil M.

2011-01-01

Maternal infection during pregnancy elevates risk for schizophrenia and related disorders in offspring. Converging evidence suggests the maternal inflammatory response mediates the interaction between maternal infection, altered brain development, and behavioral outcome. The extent to which individual differences in the maternal response to immune challenge influence the development of these abnormalities is unknown. The present study investigated the impact of individual differences in maternal response to the viral mimic polyinosinic:polycytidylic acid (poly I:C) on offspring behavior. We observed significant variability in body weight alterations of pregnant rats induced by administration of poly I:C on gestational day 14. Furthermore, the presence or absence of maternal weight loss predicted MK-801 and amphetamine stimulated locomotor abnormalities in offspring. MK-801 stimulated locomotion was altered in offspring of all poly I:C treated dams; however, the presence or absence of maternal weight loss resulted in decreased and modestly increased locomotion, respectively. Adult offspring of poly I:C treated dams that lost weight exhibited significantly decreased amphetamine stimulated locomotion, while offspring of poly I:C treated dams without weight loss performed similarly to vehicle controls. Social isolation and increased maternal age predicted weight loss in response to poly I:C but not vehicle injection. In combination, these data identify environmental factors associated with the maternal response to immune challenge and functional outcome of offspring exposed to maternal immune activation. PMID:21255612

Pathogenic mutations in TULP1 responsible for retinitis pigmentosa identified in consanguineous familial cases

PubMed Central

Ullah, Inayat; Kabir, Firoz; Iqbal, Muhammad; Gottsch, Clare Brooks S.; Naeem, Muhammad Asif; Assir, Muhammad Zaman; Khan, Shaheen N.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

2016-01-01

Purpose To identify pathogenic mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in consanguineous familial cases. Methods Seven large familial cases with multiple individuals diagnosed with retinitis pigmentosa were included in the study. Affected individuals in these families underwent ophthalmic examinations to document the symptoms and confirm the initial diagnosis. Blood samples were collected from all participating members, and genomic DNA was extracted. An exclusion analysis with microsatellite markers spanning the TULP1 locus on chromosome 6p was performed, and two-point logarithm of odds (LOD) scores were calculated. All coding exons along with the exon–intron boundaries of TULP1 were sequenced bidirectionally. We constructed a single nucleotide polymorphism (SNP) haplotype for the four familial cases harboring the K489R allele and estimated the likelihood of a founder effect. Results The ophthalmic examinations of the affected individuals in these familial cases were suggestive of RP. Exclusion analyses confirmed linkage to chromosome 6p harboring TULP1 with positive two-point LOD scores. Subsequent Sanger sequencing identified the single base pair substitution in exon14, c.1466A>G (p.K489R), in four families. Additionally, we identified a two-base deletion in exon 4, c.286_287delGA (p.E96Gfs77*); a homozygous splice site variant in intron 14, c.1495+4A>C; and a novel missense variation in exon 15, c.1561C>T (p.P521S). All mutations segregated with the disease phenotype in the respective families and were absent in ethnically matched control chromosomes. Haplotype analysis suggested (p<10−6) that affected individuals inherited the causal mutation from a common ancestor. Conclusions Pathogenic mutations in TULP1 are responsible for the RP phenotype in seven familial cases with a common ancestral mutation responsible for the disease phenotype in four of the seven families. PMID:27440997

Acute respiratory distress syndrome without identifiable risk factors: A secondary analysis of the ARDS network trials.

PubMed

Harrington, John S; Schenck, Edward J; Oromendia, Clara; Choi, Augustine M K; Siempos, Ilias I

2018-06-02

We examined whether patients with acute respiratory distress syndrome (ARDS) lacking risk factors are enrolled in therapeutic trials and assessed their clinical characteristics and outcomes. We performed a secondary analysis of patient-level data pooled from the ARMA, ALVEOLI, FACTT, ALTA and EDEN ARDSNet randomized controlled trials obtained from the Biologic Specimen and Data Repository Information Coordinating Center of the National Heart, Lung and Blood Institute. We compared baseline characteristics and clinical outcomes (before and after adjustment using Poisson regression model) of ARDS patients with versus without risk factors. Of 3733 patients with ARDS, 81 (2.2%) did not have an identifiable risk factor. Patients without risk factors were younger, had lower baseline severity of illness, were more likely to have the ARDS resolve rapidly (i.e., within 24 h) (p < 0.001) and they had more ventilator-free days (median 21; p = 0.003), more intensive care unit-free days (18; p = 0.010), and more non-pulmonary organ failure-free days (24; p < 0.001) than comparators (17, 14 and 18, respectively). Differences persisted after adjustment for potential confounders. Patients with ARDS without identifiable risk factors are enrolled in therapeutic trials and may have better outcomes, including a higher proportion of rapidly resolving ARDS, than those with risk factors. Copyright © 2018. Published by Elsevier Inc.

Compendium of Immune Signatures Identifies Conserved and Species-Specific Biology in Response to Inflammation.

PubMed

Godec, Jernej; Tan, Yan; Liberzon, Arthur; Tamayo, Pablo; Bhattacharya, Sanchita; Butte, Atul J; Mesirov, Jill P; Haining, W Nicholas

2016-01-19

Gene-expression profiling has become a mainstay in immunology, but subtle changes in gene networks related to biological processes are hard to discern when comparing various datasets. For instance, conservation of the transcriptional response to sepsis in mouse models and human disease remains controversial. To improve transcriptional analysis in immunology, we created ImmuneSigDB: a manually annotated compendium of ∼5,000 gene-sets from diverse cell states, experimental manipulations, and genetic perturbations in immunology. Analysis using ImmuneSigDB identified signatures induced in activated myeloid cells and differentiating lymphocytes that were highly conserved between humans and mice. Sepsis triggered conserved patterns of gene expression in humans and mouse models. However, we also identified species-specific biological processes in the sepsis transcriptional response: although both species upregulated phagocytosis-related genes, a mitosis signature was specific to humans. ImmuneSigDB enables granular analysis of transcriptomic data to improve biological understanding of immune processes of the human and mouse immune systems. Copyright © 2016 Elsevier Inc. All rights reserved.

Identifying context factors explaining physician's low performance in communication assessment: an explorative study in general practice.

PubMed

Essers, Geurt; van Dulmen, Sandra; van Weel, Chris; van der Vleuten, Cees; Kramer, Anneke

2011-12-13

Communication is a key competence for health care professionals. Analysis of registrar and GP communication performance in daily practice, however, suggests a suboptimal application of communication skills. The influence of context factors could reveal why communication performance levels, on average, do not appear adequate. The context of daily practice may require different skills or specific ways of handling these skills, whereas communication skills are mostly treated as generic. So far no empirical analysis of the context has been made. Our aim was to identify context factors that could be related to GP communication. A purposive sample of real-life videotaped GP consultations was analyzed (N = 17). As a frame of reference we chose the MAAS-Global, a widely used assessment instrument for medical communication. By inductive reasoning, we analyzed the GP behaviour in the consultation leading to poor item scores on the MAAS-Global. In these cases we looked for the presence of an intervening context factor, and how this might explain the actual GP communication behaviour. We reached saturation after having viewed 17 consultations. We identified 19 context factors that could potentially explain the deviation from generic recommendations on communication skills. These context factors can be categorized into doctor-related, patient-related, and consultation-related factors. Several context factors seem to influence doctor-patient communication, requiring the GP to apply communication skills differently from recommendations on communication. From this study we conclude that there is a need to explicitly account for context factors in the assessment of GP (and GP registrar) communication performance. The next step is to validate our findings.

Quantitative trait loci analyses and RNA-seq identify genes affecting stress response in rainbow trout

USDA-ARS?s Scientific Manuscript database

Genomic analyses have the potential to impact aquaculture production traits by identifying markers as proxies for traits which are expensive or difficult to measure and characterizing genetic variation and biochemical mechanisms underlying phenotypic variation. One such trait is the response of rai...

Identifying Sociological Factors for the Success of Space Exploration

NASA Astrophysics Data System (ADS)

Lundquist, C. A.; Tarter, D.; Coleman, A.

Astrosociology factors relevant to success of future space exploration may best be identified through studies of sociological circumstances of past successful explorations, such as the Apollo-Lunar Missions. These studies benefit from access to primary records of the past programs. The Archives and Special Collections Division of the Salmon Library at the University of Alabama Huntsville (UAH) houses large collections of material from the early periods of the space age. The Huntsville campus of the University of Alabama System had its birth in the mid-1950s at the time when the von Braun rocket team was relocated from Texas to Huntsville. The University, the City of Huntsville and the US Government rocket organizations developed in parallel over subsequent years. As a result, the University has a significant space heritage and focus. This is true not only for the engineering and science disciplines, but also for the social sciences. The life of the University spans the period when Huntsville government and industrial organizations were responsible for producing the rocket vehicles to first take mankind to the Moon. That endeavor was surely as significant sociologically as technologically. In the 1980s, Donald E. Tarter, conducted a series of video interviews with some leading members of the original von Braun team. Although the interviews ranged over many engineering subjects, they also recorded personal features of people involved in the Apollo lunar exploration program and the interactions between these people. Such knowledge was of course an objective. These interviews are now in the collections of the UAH Library Archives, along with extensive documentation from the same period. Under sponsorship of the Archives and the NASA-Marshall Retiree Association, the interview series was restarted in 2006 to obtain comparable oral-history interviews with more than fifty US born members of the rocket team from the 1960s. Again these video interviews are rich with

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.

Latinos in science: Identifying factors that influence the low percentage of Latino representation in the sciences

NASA Astrophysics Data System (ADS)

Miranda, Susan Jennifer

A mixed methods approach was used to identify factors that influence the underrepresentation of Latinos in the domain of science. The researcher investigated the role of family influences, academic preparation, and personal motivations to determine science-related career choices by Latinos. Binary logistic regression analyses were conducted using information from Latinos gathered from the National Education Longitudinal Study of 1988 (NELS: 88) administered by the National Center for Education Statistics. For the present study, data were analyzed using participants' responses as high school seniors, college students, and post-baccalaureates. Students responded to questions on school, work, parental academic influences, personal aspirations, and self-perception. To provide more insight into the experiences of Latinos in science and support the statistical analyses, nine students majoring in science in a private, urban university located in the northeastern part of the country were interviewed. Eleven variables related to parents' academic support and students' perceptions of parental support were taken together as predictors for two separate criteria from the survey. These results identified parents' level of education and the importance of academics to parents in their teen's college choice as significant predictors in determining college major in science. When the criterion was degree in science, the significant predictor was the frequency parents contacted high school as volunteers. Student interviews supported this information, demonstrating the importance of parental support in attaining a degree in science. Academic preparation was also analyzed. Students' reasons for taking science classes in high school was a significant predictor for science major; significant predictors for science degree were the emphasis placed on objectives in math and science classes and number of courses in biology and physics. Student interviews supported this information and

Network analysis of S. aureus response to ramoplanin reveals modules for virulence factors and resistance mechanisms and characteristic novel genes.

PubMed

Subramanian, Devika; Natarajan, Jeyakumar

2015-12-10

Staphylococcus aureus is a major human pathogen and ramoplanin is an antimicrobial attributed for effective treatment. The goal of this study was to examine the transcriptomic profiles of ramoplanin sensitive and resistant S. aureus to identify putative modules responsible for virulence and resistance-mechanisms and its characteristic novel genes. The dysregulated genes were used to reconstruct protein functional association networks for virulence-factors and resistance-mechanisms individually. Strong link between metabolic-pathways and development of virulence/resistance is suggested. We identified 15 putative modules of virulence factors. Six hypothetical genes were annotated with novel virulence activity among which SACOL0281 was discovered to be an essential virulence factor EsaD. The roles of MazEF toxin-antitoxin system, SACOL0202/SACOL0201 two-component system and that of amino-sugar and nucleotide-sugar metabolism in virulence are also suggested. In addition, 14 putative modules of resistance mechanisms including modules of ribosomal protein-coding genes and metabolic pathways such as biotin-synthesis, TCA-cycle, riboflavin-biosynthesis, peptidoglycan-biosynthesis etc. are also indicated. Copyright © 2015 Elsevier B.V. All rights reserved.

Factors involved in nurses' responses to burnout: a grounded theory study

PubMed Central

Rafii, Forough; Oskouie, Fatemeh; Nikravesh, Mansoure

2004-01-01

Background Intense and long-standing problems in burn centers in Tehran have led nurses to burnout. This phenomenon has provoked serious responses and has put the nurses, patients and the organization under pressure. The challenge for managers and nurse executives is to understand the factors which would reduce or increase the nurses' responses to burnout and develop delivery systems that promote positive adaptation and facilitate quality care. This study, as a part of more extensive research, aims to explore and describe the nurses' perceptions of the factors affecting their responses to burnout. Methods Grounded theory was used as the method. Thirty- eight participants were recruited. Data were generated by unstructured interviews and 21 sessions of participant observations. Constant comparison was used for data analysis. Results Nurses' and patients' personal characteristics and social support influenced nurses' responses to burnout. Personal characteristics of the nurses and patients, especially when interacting, had a more powerful effect. They altered emotional, attitudinal, behavioral and organizational responses to burnout and determined the kind of caring behavior. Social support had a palliative effect and altered emotional responses and some aspects of attitudinal responses. Conclusions The powerful effect of positive personal characteristics and its sensitivity to long standing and intense organizational pressures suggests approaches to executing stress reduction programs and refreshing the nurses' morale by giving more importance to ethical aspects of caring. Moreover, regarding palliative effect of social support and its importance for the nurses' wellbeing, nurse executives are responsible for promoting a work environment that supports nurses and motivates them. PMID:15541180

Multi-Level Risk Factors for Suicidal Ideation Among at-Risk Adolescent Females: The Role of Hypothalamic-Pituitary-Adrenal Axis Responses to Stress

PubMed Central

Calhoun, Casey D.; Hastings, Paul D.; Rudolph, Karen D.; Nock, Matthew K.; Prinstein, Mitchell J.

2014-01-01

Adopting a multi-level approach, this study examined risk factors for adolescent suicidal ideation, with specific attention to (a) hypothalamic-pituitary-adrenal (HPA) axis stress responses and (b) the interplay between HPA-axis and other risk factors from multiple domains (i.e., psychological, interpersonal and biological). Participants were 138 adolescent females (Mage=14.13 years, SD=1.40) at risk for suicidal behaviors. At baseline, lifetime suicidal ideation and a number of risk factors were assessed (i.e., depressive symptoms, impulsiveness, pubertal status and peer stress). Participants were exposed to a psychosocial stress task and HPA-axis responses were assessed by measuring cortisol levels pre- and post-stressor. At 3 months post-baseline, suicidal ideation again was assessed. Using group-based trajectory modeling, three groups of cortisol stress-response patterns were identified (i.e., hyporesponsive, normative, and hyperresponsive). As compared to females in the normative and hyporesponsive group, females in the hyperresponsive group were more likely to report a lifetime history of suicidal ideation at baseline, above and beyond the effects of the other predictors. Moreover, as compared to females in the normative group, females in the hyperresponsive group were at increased risk for reporting suicidal ideation 3 months later, after controlling for prior ideation. No interactions between cortisol group and the other risk factors were significant, with the exception of a non-significant trend between impulsiveness and cortisol group on lifetime suicidal ideation. Findings highlight the importance of HPA-axis responses to acute stressors as a risk factor for suicidal ideation among adolescents. PMID:24958308

Loss Factor Estimation Using the Impulse Response Decay Method on a Stiffened Structure

NASA Technical Reports Server (NTRS)

Cabell, Randolph; Schiller, Noah; Allen, Albert; Moeller, Mark

2009-01-01

High-frequency vibroacoustic modeling is typically performed using energy-based techniques such as Statistical Energy Analysis (SEA). Energy models require an estimate of the internal damping loss factor. Unfortunately, the loss factor is difficult to estimate analytically, and experimental methods such as the power injection method can require extensive measurements over the structure of interest. This paper discusses the implications of estimating damping loss factors using the impulse response decay method (IRDM) from a limited set of response measurements. An automated procedure for implementing IRDM is described and then evaluated using data from a finite element model of a stiffened, curved panel. Estimated loss factors are compared with loss factors computed using a power injection method and a manual curve fit. The paper discusses the sensitivity of the IRDM loss factor estimates to damping of connected subsystems and the number and location of points in the measurement ensemble.

The Iron-Dependent Regulation of the Candida albicans Oxidative Stress Response by the CCAAT-Binding Factor

PubMed Central

Chakravarti, Ananya; Camp, Kyle; McNabb, David S.

2017-01-01

Candida albicans is the most frequently encountered fungal pathogen in humans, capable of causing mucocutaneous and systemic infections in immunocompromised individuals. C. albicans virulence is influenced by multiple factors. Importantly, iron acquisition and avoidance of the immune oxidative burst are two critical barriers for survival in the host. Prior studies using whole genome microarray expression data indicated that the CCAAT-binding factor is involved in the regulation of iron uptake/utilization and the oxidative stress response. This study examines directly the role of the CCAAT-binding factor in regulating the expression of oxidative stress genes in response to iron availability. The CCAAT-binding factor is a heterooligomeric transcription factor previously shown to regulate genes involved in respiration and iron uptake/utilization in C. albicans. Since these pathways directly influence the level of free radicals, it seemed plausible the CCAAT-binding factor regulates genes necessary for the oxidative stress response. In this study, we show the CCAAT-binding factor is involved in regulating some oxidative stress genes in response to iron availability, including CAT1, SOD4, GRX5, and TRX1. We also show that CAT1 expression and catalase activity correlate with the survival of C. albicans to oxidative stress, providing a connection between iron obtainability and the oxidative stress response. We further explore the role of the various CCAAT-binding factor subunits in the formation of distinct protein complexes that modulate the transcription of CAT1 in response to iron. We find that Hap31 and Hap32 can compensate for each other in the formation of an active transcriptional complex; however, they play distinct roles in the oxidative stress response during iron limitation. Moreover, Hap43 was found to be solely responsible for the repression observed under iron deprivation. PMID:28122000

High responders and low responders: factors associated with individual variation in response to standardized training.

PubMed

Mann, Theresa N; Lamberts, Robert P; Lambert, Michael I

2014-08-01

The response to an exercise intervention is often described in general terms, with the assumption that the group average represents a typical response for most individuals. In reality, however, it is more common for individuals to show a wide range of responses to an intervention rather than a similar response. This phenomenon of 'high responders' and 'low responders' following a standardized training intervention may provide helpful insights into mechanisms of training adaptation and methods of training prescription. Therefore, the aim of this review was to discuss factors associated with inter-individual variation in response to standardized, endurance-type training. It is well-known that genetic influences make an important contribution to individual variation in certain training responses. The association between genotype and training response has often been supported using heritability estimates; however, recent studies have been able to link variation in some training responses to specific single nucleotide polymorphisms. It would appear that hereditary influences are often expressed through hereditary influences on the pre-training phenotype, with some parameters showing a hereditary influence in the pre-training phenotype but not in the subsequent training response. In most cases, the pre-training phenotype appears to predict only a small amount of variation in the subsequent training response of that phenotype. However, the relationship between pre-training autonomic activity and subsequent maximal oxygen uptake response appears to show relatively stronger predictive potential. Individual variation in response to standardized training that cannot be explained by genetic influences may be related to the characteristics of the training program or lifestyle factors. Although standardized programs usually involve training prescribed by relative intensity and duration, some methods of relative exercise intensity prescription may be more successful in creating

A data mining paradigm for identifying key factors in biological processes using gene expression data.

PubMed

Li, Jin; Zheng, Le; Uchiyama, Akihiko; Bin, Lianghua; Mauro, Theodora M; Elias, Peter M; Pawelczyk, Tadeusz; Sakowicz-Burkiewicz, Monika; Trzeciak, Magdalena; Leung, Donald Y M; Morasso, Maria I; Yu, Peng

2018-06-13

A large volume of biological data is being generated for studying mechanisms of various biological processes. These precious data enable large-scale computational analyses to gain biological insights. However, it remains a challenge to mine the data efficiently for knowledge discovery. The heterogeneity of these data makes it difficult to consistently integrate them, slowing down the process of biological discovery. We introduce a data processing paradigm to identify key factors in biological processes via systematic collection of gene expression datasets, primary analysis of data, and evaluation of consistent signals. To demonstrate its effectiveness, our paradigm was applied to epidermal development and identified many genes that play a potential role in this process. Besides the known epidermal development genes, a substantial proportion of the identified genes are still not supported by gain- or loss-of-function studies, yielding many novel genes for future studies. Among them, we selected a top gene for loss-of-function experimental validation and confirmed its function in epidermal differentiation, proving the ability of this paradigm to identify new factors in biological processes. In addition, this paradigm revealed many key genes in cold-induced thermogenesis using data from cold-challenged tissues, demonstrating its generalizability. This paradigm can lead to fruitful results for studying molecular mechanisms in an era of explosive accumulation of publicly available biological data.

TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF)

EPA Science Inventory

TITLE:
TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF). AUTHORS (ALL): Abbott, Barbara D.1; Best, Deborah S.1; Narotsky, Michael G.1. SPONSOR NAME: None INSTITUTIONS (ALL): 1. Repro Tox ...

Random T-DNA mutagenesis identifies a Cu-Zn-superoxide dismutase gene as a virulence factor of Sclerotinia sclerotiorum

USDA-ARS?s Scientific Manuscript database

Agrobacterium-mediated transformation (AMT) was used to identify potential virulence factors in Sclerotinia sclerotiorum. Screening AMT transformants identified two mutants showing significantly reduced virulence. The mutants showed similar growth rate, colony morphology, and sclerotial and oxalate ...

The Waardenburg Syndrome Type 4 Gene, SOX10, Is a Novel Tumor-associated Antigen Identified in a Patient with a Dramatic Response to Immunotherapy

PubMed Central

Khong, Hung T.; Rosenberg, Steven A.

2008-01-01

In this study, we have identified, for the first time, the presence of de novo cellular immune reactivity against the transcription factor SOX10, using tumor-infiltrating lymphocytes obtained from a patient who experienced a dramatic clinical response to immunotherapy. SOX10 acts as a critical transactivator of tyrosinase-related protein-2 during melanoblast development and a potent transactivator of micropthalmia-associated transcription factor, which is considered to be a master gene that controls the development and postnatal survival of melanocytes. Mutations in SOX10 result in Waardenburg syndrome type 4. The overlapping epitopes AWISKPPGV and SAWISKPPGV, designated SOX10: 332–340 and SOX10: 331–340, respectively, were recognized by tumor-infiltrating lymphocyte clone M37 in an HLA-A2-restricted fashion. PMID:12036907

Testing job typologies and identifying at-risk subpopulations using factor mixture models.

PubMed

Keller, Anita C; Igic, Ivana; Meier, Laurenz L; Semmer, Norbert K; Schaubroeck, John M; Brunner, Beatrice; Elfering, Achim

2017-10-01

Research in occupational health psychology has tended to focus on the effects of single job characteristics or various job characteristics combined into 1 factor. However, such a variable-centered approach does not account for the clustering of job attributes among groups of employees. We addressed this issue by using a person-centered approach to (a) investigate the occurrence of different empirical constellations of perceived job stressors and resources and (b) validate the meaningfulness of profiles by analyzing their association with employee well-being and performance. We applied factor mixture modeling to identify profiles in 4 large samples consisting of employees in Switzerland (Studies 1 and 2) and the United States (Studies 3 and 4). We identified 2 profiles that spanned the 4 samples, with 1 reflecting a combination of relatively low stressors and high resources (P1) and the other relatively high stressors and low resources (P3). The profiles differed mainly in terms of their organizational and social aspects. Employees in P1 reported significantly higher mean levels of job satisfaction, performance, and general health, and lower means in exhaustion compared with P3. Additional analyses showed differential relationships between job attributes and outcomes depending on profile membership. These findings may benefit organizational interventions as they show that perceived work stressors and resources more strongly influence satisfaction and well-being in particular profiles. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Diversification, phylogeny and evolution of auxin response factor (ARF) family: insights gained from analyzing maize ARF genes.

PubMed

Wang, Yijun; Deng, Dexiang; Shi, Yating; Miao, Nan; Bian, Yunlong; Yin, Zhitong

2012-03-01

Auxin response factors (ARFs), member of the plant-specific B3 DNA binding superfamily, target specifically to auxin response elements (AuxREs) in promoters of primary auxin-responsive genes and heterodimerize with Aux/IAA proteins in auxin signaling transduction cascade. In previous research, we have isolated and characterized maize Aux/IAA genes in whole-genome scale. Here, we report the comprehensive analysis of ARF genes in maize. A total of 36 ARF genes were identified and validated from the B73 maize genome through an iterative strategy. Thirty-six maize ARF genes are distributed in all maize chromosomes except chromosome 7. Maize ARF genes expansion is mainly due to recent segmental duplications. Maize ARF proteins share one B3 DNA binding domain which consists of seven-stranded β sheets and two short α helixes. Twelve maize ARFs with glutamine-rich middle regions could be as activators in modulating expression of auxin-responsive genes. Eleven maize ARF proteins are lack of homo- and heterodimerization domains. Putative cis-elements involved in phytohormones and light signaling responses, biotic and abiotic stress adaption locate in promoters of maize ARF genes. Expression patterns vary greatly between clades and sister pairs of maize ARF genes. The B3 DNA binding and auxin response factor domains of maize ARF proteins are primarily subjected to negative selection during selective sweep. The mixed selective forces drive the diversification and evolution of genomic regions outside of B3 and ARF domains. Additionally, the dicot-specific proliferation of ARF genes was detected. Comparative genomics analysis indicated that maize, sorghum and rice duplicate chromosomal blocks containing ARF homologs are highly syntenic. This study provides insights into the distribution, phylogeny and evolution of ARF gene family.

Identifying Careless Responses in Survey Data

ERIC Educational Resources Information Center

Meade, Adam W.; Craig, S. Bartholomew

2012-01-01

When data are collected via anonymous Internet surveys, particularly under conditions of obligatory participation (such as with student samples), data quality can be a concern. However, little guidance exists in the published literature regarding techniques for detecting careless responses. Previously several potential approaches have been…

[Analysis of dietary pattern and diabetes mellitus influencing factors identified by classification tree model in adults of Fujian].

PubMed

Yu, F L; Ye, Y; Yan, Y S

2017-05-10

Objective: To find out the dietary patterns and explore the relationship between environmental factors (especially dietary patterns) and diabetes mellitus in the adults of Fujian. Methods: Multi-stage sampling method were used to survey residents aged ≥18 years by questionnaire, physical examination and laboratory detection in 10 disease surveillance points in Fujian. Factor analysis was used to identify the dietary patterns, while logistic regression model was applied to analyze relationship between dietary patterns and diabetes mellitus, and classification tree model was adopted to identify the influencing factors for diabetes mellitus. Results: There were four dietary patterns in the population, including meat, plant, high-quality protein, and fried food and beverages patterns. The result of logistic analysis showed that plant pattern, which has higher factor loading of fresh fruit-vegetables and cereal-tubers, was a protective factor for non-diabetes mellitus. The risk of diabetes mellitus in the population at T2 and T3 levels of factor score were 0.727 (95 %CI: 0.561-0.943) times and 0.736 (95 %CI : 0.573-0.944) times higher, respectively, than those whose factor score was in lowest quartile. Thirteen influencing factors and eleven group at high-risk for diabetes mellitus were identified by classification tree model. The influencing factors were dyslipidemia, age, family history of diabetes, hypertension, physical activity, career, sex, sedentary time, abdominal adiposity, BMI, marital status, sleep time and high-quality protein pattern. Conclusion: There is a close association between dietary patterns and diabetes mellitus. It is necessary to promote healthy and reasonable diet, strengthen the monitoring and control of blood lipids, blood pressure and body weight, and have good lifestyle for the prevention and control of diabetes mellitus.

Hypoxia-inducible factor-1α promotes cell survival during ammonia stress response in ovarian cancer stem-like cells

PubMed Central

Kitajima, Shojiro; Lee, Kian Leong; Hikasa, Hiroki; Sun, Wendi; Huang, Ruby Yun-Ju; Yang, Henry; Matsunaga, Shinji; Yamaguchi, Takehiro; Araki, Marito; Kato, Hiroyuki

2017-01-01

Ammonia is a toxic by-product of metabolism that causes cellular stresses. Although a number of proteins are involved in adaptive stress response, specific factors that counteract ammonia-induced cellular stress and regulate cell metabolism to survive against its toxicity have yet to be identified. We demonstrated that the hypoxia-inducible factor-1α (HIF-1α) is stabilized and activated by ammonia stress. HIF-1α activated by ammonium chloride compromises ammonia-induced apoptosis. Furthermore, we identified glutamine synthetase (GS) as a key driver of cancer cell proliferation under ammonia stress and glutamine-dependent metabolism in ovarian cancer stem-like cells expressing CD90. Interestingly, activated HIF-1α counteracts glutamine synthetase function in glutamine metabolism by facilitating glycolysis and elevating glucose dependency. Our studies reveal the hitherto unknown functions of HIF-1α in a biphasic ammonia stress management in the cancer stem-like cells where GS facilitates cell proliferation and HIF-1α contributes to the metabolic remodeling in energy fuel usage resulting in attenuated proliferation but conversely promoting cell survival. PMID:29383096

ChIP-Seq Analysis for Identifying Genome-Wide Histone Modifications Associated with Stress-Responsive Genes in Plants.

PubMed

Li, Guosheng; Jagadeeswaran, Guru; Mort, Andrew; Sunkar, Ramanjulu

2017-01-01

Histone modifications represent the crux of epigenetic gene regulation essential for most biological processes including abiotic stress responses in plants. Thus, identification of histone modifications at the genome-scale can provide clues for how some genes are 'turned-on' while some others are "turned-off" in response to stress. This chapter details a step-by-step protocol for identifying genome-wide histone modifications associated with stress-responsive gene regulation using chromatin immunoprecipitation (ChIP) followed by sequencing of the DNA (ChIP-seq).

A prospective cohort study identifying risk factors for shoulder injuries in adolescent elite handball players: the Karolinska Handball Study (KHAST) study protocol.

PubMed

Asker, Martin; Waldén, Markus; Källberg, Henrik; Holm, Lena W; Skillgate, Eva

2017-11-22

factors is needed. Our study has a high potential to identify important risk factors for shoulder injuries in adolescent elite handball players owing to a large study sample, a high response rate, data collection during consecutive seasons, and recording of potential confounding factors.

Identifying behavioural differences in working donkeys in response to analgesic administration.

PubMed

Regan, F H; Hockenhull, J; Pritchard, J C; Waterman-Pearson, A E; Whay, H R

2016-01-01

To identify pain-related behaviour in working donkeys in order to assist their owners and veterinarians to recognise and manage pain. To identify general and specific behaviours associated with pain or its relief using a trial with the nonsteroidal anti-inflammatory drug meloxicam (Metacam). Observer-blinded, placebo-controlled trial. Forty adult male working donkeys with common clinical abnormalities were randomly assigned to receive either a single loading dose of meloxicam (1.2 mg/kg bwt per os; n = 20) or a placebo (30 mg honey/250 ml water per os; n = 20). Observation of postural and event behaviours was undertaken at 2 pretreatment time points followed by 4 post treatment time points, using scan (instantaneous) and focal sampling. In comparison to pretreatment baselines, donkeys receiving meloxicam were more alert post treatment than the placebo group. They were observed lying down less frequently (P = 0.007), with their eyes closed less frequently (P = 0.04) and having a high head carriage more frequently (P = 0.02). Dozing behaviour decreased after meloxicam compared with the pretreatment baseline (P = 0.03). Donkeys given meloxicam also showed more interest in their environment, turning to look at environmental stimuli more frequently (P = 0.05) than those in the placebo group post treatment. Neither the meloxicam nor the placebo group showed a significant post treatment improvement in lameness scores. Working donkeys receiving meloxicam were more active and alert compared with their pretreatment behaviour, confirming the potential value of nonsteroidal anti-inflammatory drugs in identifying behaviours indicative of pain in working donkeys. Behavioural assessment of pain in working donkeys in field clinic conditions will enable veterinary staff and owners to identify welfare issues promptly and monitor response to analgesia. The Summary is available in Chinese--see Supporting information. © 2015 EVJ Ltd.

Use of DNA Microarrays to Identify Diagnostic Signature Transcription Profiles for Host Responses to Infectious Agents

DTIC Science & Technology

2004-10-01

informative in this regard. Key signature genes will serve as the basis for rapid diagnostic approaches that could be accessed when an outbreak is suspected...AD Award Number: DAMD17-01-1-0787 TITLE: Use of DNA Microarrays to Identify Diagnostic Signature Transcription Profiles for Host Responses to...Sep 2004) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Use of DNA Microarrays to Identify Diagnostic Signature DAMD17-01-1-0787 Transcription Profiles for

Whole genome analysis using Bayesian models to identify candidate genes for immune response to vaccination

USDA-ARS?s Scientific Manuscript database

This study identified genome regions associated with variation in immune response to vaccination against bovine viral diarrhea virus type 2 (BVDV 2) in American Angus calves. Calves were born in the spring or fall of 2006-2008 (n = 620). Two doses of modified live vaccine were administered three wee...

Ethylene response factor AtERF72 negatively regulates Arabidopsis thaliana response to iron deficiency.

PubMed

Liu, Wei; Li, Qiwei; Wang, Yi; Wu, Ting; Yang, Yafei; Zhang, Xinzhong; Han, Zhenhai; Xu, Xuefeng

2017-09-23

Ethylene regulates the plant's response to stress caused by iron (Fe) deficiency. However, specific roles of ERF proteins in response to Fe deficiency remain poorly understood. Here, we investigated the role of ERF72 in response to iron deficiency in Arabidopsis thaliana. In this study, the levels of the ethylene response factor AtERF72 increased in leaves and roots induced under the iron deficient conditions. erf72 mutant plants showed increased growth compared to wild type (WT) when grown in iron deficient medium for 5 d. erf72 mutants had increased root H + velocity and the ferric reductase activity, and increase in the expression of the iron deficiency response genes iron-regulated transporter 1 (IRT1) and H + -ATPase (HA2) levels in iron deficient conditions. Compared to WT plants, erf72 mutants retained healthy chloroplast structure with significantly higher Fe and Mg content, and decreased chlorophyll degradation gene pheophorbide a oxygenase (PAO) and chlorophyllase (CLH1) expression when grown in iron deficient media. Yeast one-hybrid analysis showed that ERF72 could directly bind to the promoter regions of iron deficiency responses genes IRT1, HA2 and CLH1. Based on our results, we suggest that ethylene released from plants under iron deficiency stress can activate the expression of ERF72, which responds to iron deficiency in the negative regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Differentiating responses to contaminants from responses to other environmental factors for benthic biota in freshwater ecosystems

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

Day, K.E.; Reynoldson, T.B.; Rosenberg, D.M.

1995-12-31

Many ecological risk assessments (ERAS) of lakes, rivers and streams compare measurements of benthic community structure in specific areas of contamination to similar measurements in reference or ``clean`` areas as a basis for determining impact. However, despite numerous studies documenting alterations of benthic communities as a result of stress, the success of correctly assessing the ``health`` or degradation of these communities depends on how well responses to contamination can be discriminated from responses to other environmental factors. It is important in the ERA process to adequately describe benthic communities and to determine how natural environmental factors (e.g., substrate particle sizemore » and texture, organic content, water quality, pH, seston, etc.) may be driving benthic community structure. This knowledge is particularly important when reference areas are distant from stressed areas. This presentation will provide an overview of the environmental factors that are important in structuring natural benthic communities in rivers and lakes and discuss approaches that may be useful in differentiating between natural variability and anthropogenic stress in ERA. Several case studies from the Laurentian Great Lakes and the Fraser River watershed in British Columbia will be discussed.« less

Identification and Characterization of the Diverse Stress-Responsive R2R3-RMYB Transcription Factor from Hibiscus sabdariffa L.

PubMed Central

Mohamed, Bahaeldeen Babikar; Aftab, Beenish; Sarwar, Muhammad Bilal; Ahmad, Zarnab; Hassan, Sameera; Husnain, Tayyab

2017-01-01

Various regulatory proteins play a fundamental role to manage the healthy plant growth under stress conditions. Differential display reverse transcriptase PCR and random amplification of cDNA ends (RACE) was used to explore the osmotic stress-responsive transcripts. We identified and characterized the salt stress-responsive R2R3 type RMYB transcription factor from Hibiscus sabdariffa which has an open reading frame of 690 bp, encoding 229 long chain amino acids. In silico analysis confirmed the conserved R2 and R3 domain as well as an NLS-1 localization site. The deduced amino acids of RMYB shared 83, 81, 80, 79, 72, 71, and 66% homology with Arabidopsis thaliana, Glycine max, Oryza sativa, Zea maize, Malus domestica, Populus tremula × Populus alba, and Medicago sativa specific MYB family, respectively. We observed the gene upregulation in stem, leaf, and root tissue in response to abiotic stress. Furthermore, RMYB gene was cloned into plant expression vector under CaMV35S promoter and transformed to Gossypium hirsutum: a local cotton cultivar. Overexpression of RMYB was observed in transgenic plants under abiotic stresses which further suggests its regulatory role in response to stressful conditions. The RMYB transcription factor-overexpressing in transgenic cotton plants may be used as potential agent for the development of stress tolerant crop cultivars. PMID:29181384

Identifying At-Risk Individuals for Insomnia Using the Ford Insomnia Response to Stress Test

PubMed Central

Kalmbach, David A.; Pillai, Vivek; Arnedt, J. Todd; Drake, Christopher L.

2016-01-01

Study Objectives: A primary focus of the National Institute of Mental Health's current strategic plan is “predicting” who is at risk for disease. As such, the current investigation examined the utility of premorbid sleep reactivity in identifying a specific and manageable population at elevated risk for future insomnia. Methods: A community-based sample of adults (n = 2,892; 59.3% female; 47.9 ± 13.3 y old) with no lifetime history of insomnia or depression completed web-based surveys across three annual assessments. Participants reported parental history of insomnia, demographic characteristics, sleep reactivity on the Ford Insomnia in Response to Stress Test (FIRST), and insomnia symptoms. DSM-IV diagnostic criteria were used to determine insomnia classification. Results: Baseline FIRST scores were used to predict incident insomnia at 1-y follow-up. Two clinically meaningful FIRST cutoff values were identified: FIRST ≥ 16 (sensitivity 77%; specificity 50%; odds ratio [OR] = 2.88, P < 0.001); and FIRST ≥ 18 (sensitivity 62%; specificity 67%; OR = 3.32, P < 0.001). Notably, both FIRST cut-points outperformed known maternal (OR = 1.49–1.59, P < 0.01) and paternal history (P = NS) in predicting insomnia onset, even after controlling for stress exposure and demographic characteristics. Of the incident cases, insomniacs with highly reactive sleep systems reported longer sleep onset latencies (FIRST ≥ 16: 65 min; FIRST ≥ 18: 68 min) than participants with nonreactive insomnia (FIRST < 16: 37 min; FIRST < 18: 44 min); these groups did not differ on any other sleep parameters. Conclusions: The current study established a cost- and time-effective strategy for identifying individuals at elevated risk for insomnia based on trait sleep reactivity. The FIRST accurately identifies a focused target population in which the psychobiological processes complicit in insomnia onset and progression can be better investigated, thus improving future preventive efforts

Evolutionary genomics and HIV restriction factors.

PubMed

Pyndiah, Nitisha; Telenti, Amalio; Rausell, Antonio

2015-03-01

To provide updated insights into innate antiviral immunity and highlight prototypical evolutionary features of well characterized HIV restriction factors. Recently, a new HIV restriction factor, Myxovirus resistance 2, has been discovered and the region/residue responsible for its activity identified using an evolutionary approach. Furthermore, IFI16, an innate immunity protein known to sense several viruses, has been shown to contribute to the defense to HIV-1 by causing cell death upon sensing HIV-1 DNA. Restriction factors against HIV show characteristic signatures of positive selection. Different patterns of accelerated sequence evolution can distinguish antiviral strategies--offense or defence--as well as the level of specificity of the antiviral properties. Sequence analysis of primate orthologs of restriction factors serves to localize functional domains and sites responsible for antiviral action. We use recent discoveries to illustrate how evolutionary genomic analyses help identify new antiviral genes and their mechanisms of action.

Factors affecting study efficiency and item non-response in health surveys in developing countries: the Jamaica national healthy lifestyle survey.

PubMed

Wilks, Rainford; Younger, Novie; Mullings, Jasneth; Zohoori, Namvar; Figueroa, Peter; Tulloch-Reid, Marshall; Ferguson, Trevor; Walters, Christine; Bennett, Franklyn; Forrester, Terrence; Ward, Elizabeth; Ashley, Deanna

2007-02-28

Health surveys provide important information on the burden and secular trends of risk factors and disease. Several factors including survey and item non-response can affect data quality. There are few reports on efficiency, validity and the impact of item non-response, from developing countries. This report examines factors associated with item non-response and study efficiency in a national health survey in a developing Caribbean island. A national sample of participants aged 15-74 years was selected in a multi-stage sampling design accounting for 4 health regions and 14 parishes using enumeration districts as primary sampling units. Means and proportions of the variables of interest were compared between various categories. Non-response was defined as failure to provide an analyzable response. Linear and logistic regression models accounting for sample design and post-stratification weighting were used to identify independent correlates of recruitment efficiency and item non-response. We recruited 2012 15-74 year-olds (66.2% females) at a response rate of 87.6% with significant variation between regions (80.9% to 97.6%; p < 0.0001). Females outnumbered males in all parishes. The majority of subjects were recruited in a single visit, 39.1% required multiple visits varying significantly by region (27.0% to 49.8% [p < 0.0001]). Average interview time was 44.3 minutes with no variation between health regions, urban-rural residence, educational level, gender and SES; but increased significantly with older age category from 42.9 minutes in the youngest to 46.0 minutes in the oldest age category. Between 15.8% and 26.8% of persons did not provide responses for the number of sexual partners in the last year. Women and urban residents provided less data than their counterparts. Highest item non-response related to income at 30% with no gender difference but independently related to educational level, employment status, age group and health region. Characteristics of non

Structural-Vibration-Response Data Analysis

NASA Technical Reports Server (NTRS)

Smith, W. R.; Hechenlaible, R. N.; Perez, R. C.

1983-01-01

Computer program developed as structural-vibration-response data analysis tool for use in dynamic testing of Space Shuttle. Program provides fast and efficient time-domain least-squares curve-fitting procedure for reducing transient response data to obtain structural model frequencies and dampings from free-decay records. Procedure simultaneously identifies frequencies, damping values, and participation factors for noisy multiple-response records.

Serum Proteome Signature of Radiation Response: Upregulation of Inflammation-Related Factors and Downregulation of Apolipoproteins and Coagulation Factors in Cancer Patients Treated With Radiation Therapy—A Pilot Study

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

Widlak, Piotr, E-mail: widlak@io.gliwice.pl; Jelonek, Karol; Wojakowska, Anna

Purpose: Ionizing radiation affects the proteome of irradiated cells and tissue, yet data concerning changes induced during radiation therapy (RT) in human blood are fragmentary and inconclusive. We aimed to identify features of serum proteome and associated processes involved in response to partial body irradiation during cancer treatment. Methods and Materials: Twenty patients with head and neck squamous cell cancer (HNSCC) and 20 patients with prostate cancer received definitive intensity modulated RT. Blood samples were collected before RT, just after RT, and 1 month after the end of RT. Complete serum proteome was analyzed in individual samples, using a shotgun liquidmore » chromatography-tandem mass spectrometry approach which allowed identification of approximately 450 proteins. Approximately 100 unique proteins were quantified in all samples after exclusion of immunoglobulins, and statistical significance of differences among consecutive samples was assessed. Processes associated with quantified proteins and their functional interactions were predicted using gene ontology tools. Results: RT-induced changes were marked in the HNSCC patient group: 22 upregulated and 33 downregulated proteins were detected in post-RT sera. Most of the changes reversed during follow-up, yet levels of some proteins remained affected 1 month after the end of RT. RT-upregulated proteins were associated with acute phase, inflammatory response, and complement activation. RT-downregulated proteins were associated with transport and metabolism of lipids (plasma apolipoproteins) and blood coagulation. RT-induced changes were much weaker in prostate cancer patients, which corresponded to differences in acute radiation toxicity observed in both groups. Nevertheless, general patterns of RT-induced sera proteome changes were similar in both of the groups of cancer patients. Conclusions: In this pilot study, we proposed to identify a molecular signature of radiation response, based on

The Small Ethylene Response Factor ERF96 is Involved in the Regulation of the Abscisic Acid Response in Arabidopsis

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

Wang, Xiaoping; Liu, Shanda; Tian, Hainan

We report that ethylene regulates many aspects of plant growth and development including seed germination, leaf senescence, and fruit ripening, and of plant responses to environmental stimuli including both biotic and abiotic stresses. Ethylene response factors (ERFs) are plant-specific transcription factors and are a subfamily of the AP2 (APETALA2)/ERF transcription factor family. The function of many members in this large gene family remains largely unknown. ERF96, a member of the Group IX ERF family transcription factors, has recently been shown to be a transcriptional activator that is involved in plant defense response in Arabidopsis. Here we provide evidence that ERF96more » is a positive regulator of abscisic acid (ABA) responses. Bioinformatics analysis indicated that there are a total four small ERFs in Arabidopsis including ERF95, ERF96, ERF97, and ERF98, and that ERF96 forms a cluster with ERF95 and ERF97. By using quantitative RT-PCR, we found that ERF96 is expressed in all tissues and organs examined except roots, with relatively high expression in flowers and seeds. Results from the protoplast transfection assay indicated that the EDLL motif-containing C-terminal domain is responsible for ERF96’s transcriptional activity. Although loss-of-function mutant of ERF96 was morphologically similar to wild type plants, transgenic plants overexpressing ERF96 had smaller rosette size and were delayed in flowering time. In ABA sensitivity assays, we found that ERF96 overexpression plants were hypersensitive to ABA in terms of ABA inhibition of seed germination, early seedling development and root elongation. Consistent with these observations, elevated transcript levels of some ABA-responsive genes including RD29A, ABI5, ABF3, ABF4, P5CS, and COR15A were observed in the transgenic plants in the presence of ABA. However, in the absence of ABA treatment, the transcript levels of these ABA-responsive genes remained largely unchanged. Our experiments also showed

The Small Ethylene Response Factor ERF96 is Involved in the Regulation of the Abscisic Acid Response in Arabidopsis

DOE PAGES

Wang, Xiaoping; Liu, Shanda; Tian, Hainan; ...

2015-11-26

We report that ethylene regulates many aspects of plant growth and development including seed germination, leaf senescence, and fruit ripening, and of plant responses to environmental stimuli including both biotic and abiotic stresses. Ethylene response factors (ERFs) are plant-specific transcription factors and are a subfamily of the AP2 (APETALA2)/ERF transcription factor family. The function of many members in this large gene family remains largely unknown. ERF96, a member of the Group IX ERF family transcription factors, has recently been shown to be a transcriptional activator that is involved in plant defense response in Arabidopsis. Here we provide evidence that ERF96more » is a positive regulator of abscisic acid (ABA) responses. Bioinformatics analysis indicated that there are a total four small ERFs in Arabidopsis including ERF95, ERF96, ERF97, and ERF98, and that ERF96 forms a cluster with ERF95 and ERF97. By using quantitative RT-PCR, we found that ERF96 is expressed in all tissues and organs examined except roots, with relatively high expression in flowers and seeds. Results from the protoplast transfection assay indicated that the EDLL motif-containing C-terminal domain is responsible for ERF96’s transcriptional activity. Although loss-of-function mutant of ERF96 was morphologically similar to wild type plants, transgenic plants overexpressing ERF96 had smaller rosette size and were delayed in flowering time. In ABA sensitivity assays, we found that ERF96 overexpression plants were hypersensitive to ABA in terms of ABA inhibition of seed germination, early seedling development and root elongation. Consistent with these observations, elevated transcript levels of some ABA-responsive genes including RD29A, ABI5, ABF3, ABF4, P5CS, and COR15A were observed in the transgenic plants in the presence of ABA. However, in the absence of ABA treatment, the transcript levels of these ABA-responsive genes remained largely unchanged. Our experiments also showed

Surveys of Health Professions Trainees: Prevalence, Response Rates, and Predictive Factors to Guide Researchers.

PubMed

Phillips, Andrew W; Friedman, Benjamin T; Utrankar, Amol; Ta, Andrew Q; Reddy, Shalini T; Durning, Steven J

2017-02-01

To establish a baseline overall response rate for surveys of health professions trainees, determine strategies associated with improved response rates, and evaluate for the presence of nonresponse bias. The authors performed a comprehensive analysis of all articles published in Academic Medicine, Medical Education, and Advances in Health Sciences Education in 2013, recording response rates. Additionally, they reviewed nonresponse bias analyses and factors suggested in other fields to affect response rate including survey delivery method, prenotification, and incentives. The search yielded 732 total articles; of these, 356 were research articles, and of these, 185 (52.0%) used at least one survey. Of these, 66 articles (35.6%) met inclusion criteria and yielded 73 unique surveys. Of the 73 surveys used, investigators reported a response rate for 63.0% of them; response rates ranged from 26.6% to 100%, mean (standard deviation) 71.3% (19.5%). Investigators reported using incentives for only 16.4% of the 73 surveys. The only survey methodology factor significantly associated with response rate was single- vs. multi-institutional surveys (respectively, 74.6% [21.2%] vs. 62.0% [12.8%], P = .022). Notably, statistical power for all analyses was limited. No articles evaluated for nonresponse bias. Approximately half of the articles evaluated used a survey as part of their methods. Limited data are available to establish a baseline response rate among health professions trainees and inform researchers which strategies are associated with higher response rates. Journals publishing survey-based health professions education research should improve reporting of response rate, nonresponse bias, and other survey factors.

Individual differences in response to automation: the five factor model of personality.

PubMed

Szalma, James L; Taylor, Grant S

2011-06-01

This study examined the relationship of operator personality (Five Factor Model) and characteristics of the task and of adaptive automation (reliability and adaptiveness-whether the automation was well-matched to changes in task demand) to operator performance, workload, stress, and coping. This represents the first investigation of how the Five Factors relate to human response to automation. One-hundred-sixty-one college students experienced either 75% or 95% reliable automation provided with task loads of either two or four displays to be monitored. The task required threat detection in a simulated uninhabited ground vehicle (UGV) task. Task demand exerted the strongest influence on outcome variables. Automation characteristics did not directly impact workload or stress, but effects did emerge in the context of trait-task interactions that varied as a function of the dimension of workload and stress. The pattern of relationships of traits to dependent variables was generally moderated by at least one task factor. Neuroticism was related to poorer performance in some conditions, and all five traits were associated with at least one measure of workload and stress. Neuroticism generally predicted increased workload and stress and the other traits predicted decreased levels of these states. However, in the case of the relation of Extraversion and Agreeableness to Worry, Frustration, and avoidant coping, the direction of effects varied across task conditions. The results support incorporation of individual differences into automation design by identifying the relevant person characteristics and using the information to determine what functions to automate and the form and level of automation.

UV-B-Responsive Association of the Arabidopsis bZIP Transcription Factor ELONGATED HYPOCOTYL5 with Target Genes, Including Its Own Promoter[W][OPEN

PubMed Central

Binkert, Melanie; Kozma-Bognár, László; Terecskei, Kata; De Veylder, Lieven; Nagy, Ferenc; Ulm, Roman

2014-01-01

In plants subjected to UV-B radiation, responses are activated that minimize damage caused by UV-B. The bZIP transcription factor ELONGATED HYPOCOTYL5 (HY5) acts downstream of the UV-B photoreceptor UV RESISTANCE LOCUS8 (UVR8) and promotes UV-B-induced photomorphogenesis and acclimation. Expression of HY5 is induced by UV-B; however, the transcription factor(s) that regulate HY5 transcription in response to UV-B and the impact of UV-B on the association of HY5 with its target promoters are currently unclear. Here, we show that HY5 binding to the promoters of UV-B-responsive genes is enhanced by UV-B in a UVR8-dependent manner in Arabidopsis thaliana. In agreement, overexpression of REPRESSOR OF UV-B PHOTOMORPHOGENESIS2, a negative regulator of UVR8 function, blocks UV-B-responsive HY5 enrichment at target promoters. Moreover, we have identified a T/G-box in the HY5 promoter that is required for its UV-B responsiveness. We show that HY5 and its homolog HYH bind to the T/GHY5-box cis-acting element and that they act redundantly in the induction of HY5 expression upon UV-B exposure. Therefore, HY5 is enriched at target promoters in response to UV-B in a UVR8 photoreceptor-dependent manner, and HY5 and HYH interact directly with a T/G-box cis-acting element of the HY5 promoter, mediating the transcriptional activation of HY5 in response to UV-B. PMID:25351492

Absolute Measurements of Macrophage Migration Inhibitory Factor and Interleukin-1-β mRNA Levels Accurately Predict Treatment Response in Depressed Patients.

PubMed

Cattaneo, Annamaria; Ferrari, Clarissa; Uher, Rudolf; Bocchio-Chiavetto, Luisella; Riva, Marco Andrea; Pariante, Carmine M

2016-10-01

Increased levels of inflammation have been associated with a poorer response to antidepressants in several clinical samples, but these findings have had been limited by low reproducibility of biomarker assays across laboratories, difficulty in predicting response probability on an individual basis, and unclear molecular mechanisms. Here we measured absolute mRNA values (a reliable quantitation of number of molecules) of Macrophage Migration Inhibitory Factor and interleukin-1β in a previously published sample from a randomized controlled trial comparing escitalopram vs nortriptyline (GENDEP) as well as in an independent, naturalistic replication sample. We then used linear discriminant analysis to calculate mRNA values cutoffs that best discriminated between responders and nonresponders after 12 weeks of antidepressants. As Macrophage Migration Inhibitory Factor and interleukin-1β might be involved in different pathways, we constructed a protein-protein interaction network by the Search Tool for the Retrieval of Interacting Genes/Proteins. We identified cutoff values for the absolute mRNA measures that accurately predicted response probability on an individual basis, with positive predictive values and specificity for nonresponders of 100% in both samples (negative predictive value=82% to 85%, sensitivity=52% to 61%). Using network analysis, we identified different clusters of targets for these 2 cytokines, with Macrophage Migration Inhibitory Factor interacting predominantly with pathways involved in neurogenesis, neuroplasticity, and cell proliferation, and interleukin-1β interacting predominantly with pathways involved in the inflammasome complex, oxidative stress, and neurodegeneration. We believe that these data provide a clinically suitable approach to the personalization of antidepressant therapy: patients who have absolute mRNA values above the suggested cutoffs could be directed toward earlier access to more assertive antidepressant strategies

Job stress factors, stress response, and social support in association with insomnia of Japanese male workers.

PubMed

Nishitani, Naoko; Sakakibara, Hisataka

2010-01-01

The aim of the present study was to examine the relation of insomnia with job stress factors, stress response, and social support. A self-completed questionnaire survey was conducted in 212 male Japanese workers at a synthetic fiber plant. With regard to insomnia, subjects were asked the first 5 of the 8 questions on the Athens Insomnia Scale (AIS). Job stress factors, stress response and social support were assessed using the Job Stress Questionnaire. Multiple regression analyses showed that psychological job stress factors of poor appropriateness of work and high qualitative workload were associated with insomnia. The psychological stress response of depression and physical stress responses were also related with insomnia. Depression was also related to appropriateness of work. The present results showed that insomnia was closely related with the psychological job stress factor of appropriateness of work and the psychological response of depression. These mutual relationships between insomnia and poor mental health need be investigated further.

Identifying critical factors influencing the disposal of dead pigs by farmers in China.

PubMed

Wu, Linhai; Xu, Guoyan; Wang, Xiaoli

2016-01-01

Disposal of dead pigs by pig farmers may have a direct impact on pork safety, public health, and the ecological environment in China. Drawing on the existing literature, this study analyzed and summarized the main factors that could affect the disposal of dead pigs by pig farmers by conducting a survey of 654 pig farmers in Funing County, Jiangsu Province, China. The purpose of this analysis was to investigate the disposal of dead pigs in China and provide useful regulatory strategies for the government. The interrelationships among dimensions and factors that affect the disposal of dead pigs by farmers were analyzed, and critical factors were identified by a hybrid multi-criteria decision-making method, which is a combination of decision-making trial and evaluation laboratory (DEMATEL) and analytic network process (ANP). Our results demonstrated that production characteristics were the most important dimensions and that costs and profits, scale of farming, pattern of farming, knowledge of relevant laws and regulations, and knowledge of pig disease and prevention were the five most critical factors affecting the disposal of dead pigs by farmers in China at this stage. The significance of this study lies in further discussing some management policies for the Chinese government regarding strengthen regulation of disposing dead pigs.

Identifying Environmental and Social Factors Predisposing to Pathological Gambling Combining Standard Logistic Regression and Logic Learning Machine.

PubMed

Parodi, Stefano; Dosi, Corrado; Zambon, Antonella; Ferrari, Enrico; Muselli, Marco

2017-12-01

Identifying potential risk factors for problem gambling (PG) is of primary importance for planning preventive and therapeutic interventions. We illustrate a new approach based on the combination of standard logistic regression and an innovative method of supervised data mining (Logic Learning Machine or LLM). Data were taken from a pilot cross-sectional study to identify subjects with PG behaviour, assessed by two internationally validated scales (SOGS and Lie/Bet). Information was obtained from 251 gamblers recruited in six betting establishments. Data on socio-demographic characteristics, lifestyle and cognitive-related factors, and type, place and frequency of preferred gambling were obtained by a self-administered questionnaire. The following variables associated with PG were identified: instant gratification games, alcohol abuse, cognitive distortion, illegal behaviours and having started gambling with a relative or a friend. Furthermore, the combination of LLM and LR indicated the presence of two different types of PG, namely: (a) daily gamblers, more prone to illegal behaviour, with poor money management skills and who started gambling at an early age, and (b) non-daily gamblers, characterised by superstitious beliefs and a higher preference for immediate reward games. Finally, instant gratification games were strongly associated with the number of games usually played. Studies on gamblers habitually frequently betting shops are rare. The finding of different types of PG by habitual gamblers deserves further analysis in larger studies. Advanced data mining algorithms, like LLM, are powerful tools and potentially useful in identifying risk factors for PG.

Identifying community thresholds for lotic benthic diatoms in response to human disturbance.

PubMed

Tang, Tao; Tang, Ting; Tan, Lu; Gu, Yuan; Jiang, Wanxiang; Cai, Qinghua

2017-06-23

Although human disturbance indirectly influences lotic assemblages through modifying physical and chemical conditions, identifying thresholds of human disturbance would provide direct evidence for preventing anthropogenic degradation of biological conditions. In the present study, we used data obtained from tributaries of the Three Gorges Reservoir in China to detect effects of human disturbance on streams and to identify disturbance thresholds for benthic diatoms. Diatom species composition was significantly affected by three in-stream stressors including TP, TN and pH. Diatoms were also influenced by watershed % farmland and natural environmental variables. Considering three in-stream stressors, TP was positively influenced by % farmland and % impervious surface area (ISA). In contrast, TN and pH were principally affected by natural environmental variables. Among measured natural environmental variables, average annual air temperature, average annual precipitation, and topsoil % CaCO 3 , % gravel, and total exchangeable bases had significant effects on study streams. When effects of natural variables were accounted for, substantial compositional changes in diatoms occurred when farmland or ISA land use exceeded 25% or 0.3%, respectively. Our study demonstrated the rationale for identifying thresholds of human disturbance for lotic assemblages and addressed the importance of accounting for effects of natural factors for accurate disturbance thresholds.

The ETHYLENE RESPONSE FACTORs ERF6 and ERF11 Antagonistically Regulate Mannitol-Induced Growth Inhibition in Arabidopsis1[OPEN

PubMed Central

Dubois, Marieke; Van den Broeck, Lisa; Claeys, Hannes; Van Vlierberghe, Kaatje; Matsui, Minami; Inzé, Dirk

2015-01-01

Leaf growth is a tightly regulated and complex process, which responds in a dynamic manner to changing environmental conditions, but the mechanisms that reduce growth under adverse conditions are rather poorly understood. We previously identified a growth inhibitory pathway regulating leaf growth upon exposure to a low concentration of mannitol and characterized the ETHYLENE RESPONSE FACTOR (ERF)/APETALA2 transcription factor ERF6 as a central activator of both leaf growth inhibition and induction of stress tolerance genes. Here, we describe the role of the transcriptional repressor ERF11 in relation to the ERF6-mediated stress response in Arabidopsis (Arabidopsis thaliana). Using inducible overexpression lines, we show that ERF6 induces the expression of ERF11. ERF11 in turn molecularly counteracts the action of ERF6 and represses at least some of the ERF6-induced genes by directly competing for the target gene promoters. As a phenotypical consequence of the ERF6-ERF11 antagonism, the extreme dwarfism caused by ERF6 overexpression is suppressed by overexpression of ERF11. Together, our data demonstrate that dynamic mechanisms exist to fine-tune the stress response and that ERF11 counteracts ERF6 to maintain a balance between plant growth and stress defense. PMID:25995327

Diabetes insipidus is an unfavorable prognostic factor for response to glucocorticoids in patients with autoimmune hypophysitis.

PubMed

Lupi, Isabella; Cosottini, Mirco; Caturegli, Patrizio; Manetti, Luca; Urbani, Claudio; Cappellani, Daniele; Scattina, Ilaria; Martino, Enio; Marcocci, Claudio; Bogazzi, Fausto

2017-08-01

Autoimmune hypophysitis (AH) has a variable clinical presentation and natural history; likewise, its response to glucocorticoid therapy is often unpredictable. To identify clinical and radiological findings associated with response to glucocorticoids. 12 consecutive patients with AH, evaluated from 2008 to 2016. AH was the exclusion diagnosis after ruling out other pituitary masses and secondary causes of hypophysitis. Mean follow-up time was 30 ± 27 months (range 12-96 months). MRI identified two main patterns of presentation: global enlargement of the pituitary gland or panhypophysitis ( n  = 4, PH), and pituitary stalk abnormality only, or infundibulo-neuro-hypophysitis ( n  = 8, INH). Multiple tropin defects were more common in PH (100%) than those in INH (28% P  = 0.014), whereas diabetes insipidus was more common in INH (100%) than that in PH (50%; P  = 0.028). All 4 PH and 4 out of 8 INH were treated with glucocorticoids. Pituitary volume significantly reduced in all PH patients ( P  = 0.012), defective anterior pituitary function recovered only in the two patients without diabetes insipidus (50%) and panhypopituitarism persisted, along with diabetes insipidus, in the remaining 2 (50%). In all INH patients, either treated or untreated, pituitary stalk diameter reduced ( P  = 0.008) but diabetes insipidus persisted in all. Glucocorticoid therapy may improve anterior pituitary function in a subset of patients but has no effect on restoring posterior pituitary function. Diabetes insipidus appears as a negative prognostic factor for response to glucocorticoids. © 2017 European Society of Endocrinology.

Factors associated with clinical and virological response in patients treated with oseltamivir or zanamivir for influenza A during the 2008-2009 winter.

PubMed

Blanchon, T; Mentré, F; Charlois-Ou, C; Dornic, Q; Mosnier, A; Bouscambert, M; Carrat, F; Duval, X; Enouf, V; Leport, C

2013-02-01

Oseltamivir or zanamivir are effective in outpatients with seasonal influenza; however, factors associated with response have been incompletely described. During the 2008/2009 epidemic, in a randomized trial for influenza A-infected outpatients, clinical (time to alleviation of flu-related symptoms) and virological (rate of patients with day 2 nasal viral load <200 cgeq/μL) responses to oseltamivir or zanamivir were assessed and associated factors were determined using multivariate analysis. For oseltamivir (141 patients) and zanamivir (149 patients) median times to alleviation of symptoms were 3 and 4 days, respectively; 59% and 34% had virological response. For oseltamivir, a lower clinical response was associated with female gender (HR, 0.53; 95% CI, 0.36-0.79), baseline symptoms score >14 (HR, 0.47; 0.32-0.70), viral load ≥5 log cgeq/μL (HR, 0.63; 0.43-0.93), and initiation of antibiotics (HR, 0.30; 0.12-0.76); a lower virological response was associated with female gender (OR, 0.45; 0.21-0.96), baseline viral load ≥5 log cgeq/μL (OR, 0.40; 0.20-0.84) and days 0-2 incomplete compliance (OR, 0.31; 0.10-0.98). For zanamivir, virological response was associated with age ≥50 years (OR, 0.29; 0.10-0.85) and initiation of antibiotics at baseline (OR, 4.24; 1.07-17.50). Factors associated with lower response to neuraminidase inhibitors in outpatients appeared to be easily identifiable during routine clinical examination and, when appropriate, by nasal sampling at baseline. The unknown association between gender and response to oseltamivir was not explained by compliance. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

A novel ethylene responsive factor CitERF13 plays a role in photosynthesis regulation.

PubMed

Xie, Xiu-Lan; Xia, Xiao-Jian; Kuang, Sheng; Zhang, Xi-Li; Yin, Xue-Ren; Yu, Jing-Quan; Chen, Kun-Song

2017-03-01

Ethylene responsive factors (ERFs) act as critical downstream components of the ethylene signalling pathway in regulating plant development and stress responses. However little is known about its role in regulation of photosynthesis. Here, we identified an ethylene-inducible ERF gene in citrus, CitERF13. Transient over-expression of CitERF13 in N. tabacum leaves, resulted in a significant decrease in net photosynthetic rate. Closer examination of photosynthetic activity of PSII and PSI indicated that CitERF13 overexpression led to declines of F v /F m , Y(II) and Y(I). However, change in NPQ was less pronounced. CitERF13 overexpression also significantly reduced V c,max , J max and AQY, indicating inhibition of the Calvin cycle. The expression of photosynthesis-related genes was suppressed to a variable extent in leaf blades transiently over-expressing CitERF13. CitERF13 transient overexpression in tobacco or citrus both resulted in a decline of Chlorophyll content and CitERF13 overexpressing tobacco leaf disc was more susceptible to chlorosis in response to MV-mediated oxidative stress. The results suggest that CitERF13 is potentially involved in suppressing photosynthesis through multiple pathways, for instance, inhibiting photochemical activity of photosynthesis, CO 2 carboxylation capacity and chlorophyll metabolism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Plasma membrane proteome analysis identifies a role of barley membrane steroid binding protein in root architecture response to salinity.

PubMed

Witzel, Katja; Matros, Andrea; Møller, Anders L B; Ramireddy, Eswarayya; Finnie, Christine; Peukert, Manuela; Rutten, Twan; Herzog, Andreas; Kunze, Gotthard; Melzer, Michael; Kaspar-Schoenefeld, Stephanie; Schmülling, Thomas; Svensson, Birte; Mock, Hans-Peter

2018-06-01

Although the physiological consequences of plant growth under saline conditions have been well described, understanding the core mechanisms conferring plant salt adaptation has only started. We target the root plasma membrane proteomes of two barley varieties, cvs. Steptoe and Morex, with contrasting salinity tolerance. In total, 588 plasma membrane proteins were identified by mass spectrometry, of which 182 were either cultivar or salinity stress responsive. Three candidate proteins with increased abundance in the tolerant cv. Morex were involved either in sterol binding (a GTPase-activating protein for the adenosine diphosphate ribosylation factor [ZIGA2], and a membrane steroid binding protein [MSBP]) or in phospholipid synthesis (phosphoethanolamine methyltransferase [PEAMT]). Overexpression of barley MSBP conferred salinity tolerance to yeast cells, whereas the knock-out of the heterologous AtMSBP1 increased salt sensitivity in Arabidopsis. Atmsbp1 plants showed a reduced number of lateral roots under salinity, and root-tip-specific expression of barley MSBP in Atmsbp1 complemented this phenotype. In barley, an increased abundance of MSBP correlates with reduced root length and lateral root formation as well as increased levels of auxin under salinity being stronger in the tolerant cv. Morex. Hence, we concluded the involvement of MSBP in phytohormone-directed adaptation of root architecture in response to salinity. © 2018 John Wiley & Sons Ltd.

Cadmium, cobalt and lead cause stress response, cell cycle deregulation and increased steroid as well as xenobiotic metabolism in primary normal human bronchial epithelial cells which is coordinated by at least nine transcription factors.

PubMed

Glahn, Felix; Schmidt-Heck, Wolfgang; Zellmer, Sebastian; Guthke, Reinhard; Wiese, Jan; Golka, Klaus; Hergenröder, Roland; Degen, Gisela H; Lehmann, Thomas; Hermes, Matthias; Schormann, Wiebke; Brulport, Marc; Bauer, Alexander; Bedawy, Essam; Gebhardt, Rolf; Hengstler, Jan G; Foth, Heidi

2008-08-01

Workers occupationally exposed to cadmium, cobalt and lead have been reported to have increased levels of DNA damage. To analyze whether in vivo relevant concentrations of heavy metals cause systematic alterations in RNA expression patterns, we performed a gene array study using primary normal human bronchial epithelial cells. Cells were incubated with 15 microg/l Cd(II), 25 microg/l Co(II) and 550 microg/l Pb(II) either with individual substances or in combination. Differentially expressed genes were filtered out and used to identify enriched GO categories as well as KEGG pathways and to identify transcription factors whose binding sites are enriched in a given set of promoters. Interestingly, combined exposure to Cd(II), Co(II) and Pb(II) caused a coordinated response of at least seven stress response-related transcription factors, namely Oct-1, HIC1, TGIF, CREB, ATF4, SRF and YY1. A stress response was further corroborated by up regulation of genes involved in glutathione metabolism. A second major response to heavy metal exposure was deregulation of the cell cycle as evidenced by down regulation of the transcription factors ELK-1 and the Ets transcription factor GABP, as well as deregulation of genes involved in purine and pyrimidine metabolism. A third and surprising response was up regulation of genes involved in steroid metabolism, whereby promoter analysis identified up regulation of SRY that is known to play a role in sex determination. A forth response was up regulation of xenobiotic metabolising enzymes, particularly of dihydrodiol dehydrogenases 1 and 2 (AKR1C1, AKR1C2). Incubations with individual heavy metals showed that the response of AKR1C1 and AKR1C2 was predominantly caused by lead. In conclusion, we have shown that in vivo relevant concentrations of Cd(II), Co(II) and Pb(II) cause a complex and coordinated response in normal human bronchial epithelial cells. This study gives an overview of the most responsive genes.

Rice homeobox transcription factor HOX1a positively regulates gibberellin responses by directly suppressing EL1.

PubMed

Wen, Bi-Qing; Xing, Mei-Qing; Zhang, Hua; Dai, Cheng; Xue, Hong-Wei

2011-11-01

Homeobox transcription factors are involved in various aspects of plant development, including maintenance of the biosynthesis and signaling pathways of different hormones. However, few direct targets of homeobox proteins have been identified. We here show that overexpression of rice homeobox gene HOX1a resulted in enhanced gibberellin (GA) response, indicating a positive effect of HOX1a in GA signaling. HOX1a is induced by GA and encodes a homeobox transcription factor with transcription repression activity. In addition, HOX1a suppresses the transcription of early flowering1 (EL1), a negative regulator of GA signaling, and further electrophoretic mobility shift assay and chromatin immunoprecipitation analysis revealed that HOX1a directly bound to the promoter region of EL1 to suppress its expression and stimulate GA signaling. These results demonstrate that HOX1a functions as a positive regulator of GA signaling by suppressing EL1, providing informative hints on the study of GA signaling. © 2011 Institute of Botany, Chinese Academy of Sciences.

Manipulation of Auxin Response Factor 19 affects seed size in the woody perennial Jatropha curcas

PubMed Central

Sun, Yanwei; Wang, Chunming; Wang, Ning; Jiang, Xiyuan; Mao, Huizhu; Zhu, Changxiang; Wen, Fujiang; Wang, Xianghua; Lu, Zhijun; Yue, Genhua; Xu, Zengfu; Ye, Jian

2017-01-01

Seed size is a major determinant of seed yield but few is known about the genetics controlling of seed size in plants. Phytohormones cytokinin and brassinosteroid were known to be involved in the regulation of herbaceous plant seed development. Here we identified a homolog of Auxin Response Factor 19 (JcARF19) from a woody plant Jatropha curcas and genetically demonstrated its functions in controlling seed size and seed yield. Through Virus Induced Gene Silencing (VIGS), we found that JcARF19 was a positive upstream modulator in auxin signaling and may control plant organ size in J. curcas. Importantly, transgenic overexpression of JcARF19 significantly increased seed size and seed yield in plants Arabidopsis thaliana and J. curcas, indicating the importance of auxin pathway in seed yield controlling in dicot plants. Transcripts analysis indicated that ectopic expression of JcARF19 in J. curcas upregulated auxin responsive genes encoding essential regulators in cell differentiation and cytoskeletal dynamics of seed development. Our data suggested the potential of improving seed traits by precisely engineering auxin signaling in woody perennial plants. PMID:28102350

Objective Model Selection for Identifying the Human Feedforward Response in Manual Control.

PubMed

Drop, Frank M; Pool, Daan M; van Paassen, Marinus Rene M; Mulder, Max; Bulthoff, Heinrich H

2018-01-01

Realistic manual control tasks typically involve predictable target signals and random disturbances. The human controller (HC) is hypothesized to use a feedforward control strategy for target-following, in addition to feedback control for disturbance-rejection. Little is known about human feedforward control, partly because common system identification methods have difficulty in identifying whether, and (if so) how, the HC applies a feedforward strategy. In this paper, an identification procedure is presented that aims at an objective model selection for identifying the human feedforward response, using linear time-invariant autoregressive with exogenous input models. A new model selection criterion is proposed to decide on the model order (number of parameters) and the presence of feedforward in addition to feedback. For a range of typical control tasks, it is shown by means of Monte Carlo computer simulations that the classical Bayesian information criterion (BIC) leads to selecting models that contain a feedforward path from data generated by a pure feedback model: "false-positive" feedforward detection. To eliminate these false-positives, the modified BIC includes an additional penalty on model complexity. The appropriate weighting is found through computer simulations with a hypothesized HC model prior to performing a tracking experiment. Experimental human-in-the-loop data will be considered in future work. With appropriate weighting, the method correctly identifies the HC dynamics in a wide range of control tasks, without false-positive results.

Advance to and Persistence in Graduate School: Identifying the Influential Factors and Major-Based Differences

ERIC Educational Resources Information Center

Xu, Yonghong Jade

2014-01-01

Structured within an expanded econometric theoretical framework, this study uses national data sources to identify the critical factors that influence college graduates' advance to and persistence in graduate education and to compare the systematic differences between students in the STEM and non-STEM majors. The findings indicate that there is a…

Nonlinear Local Bending Response and Bulging Factors for Longitudinal and Circumferential Cracks in Pressurized Cylindrical Shells

NASA Technical Reports Server (NTRS)

Young, Richard D.; Rose, Cheryl A.; Starnes, James H., Jr.

2000-01-01

Results of a geometrically nonlinear finite element parametric study to determine curvature correction factors or bulging factors that account for increased stresses due to curvature for longitudinal and circumferential cracks in unstiffened pressurized cylindrical shells are presented. Geometric parameters varied in the study include the shell radius, the shell wall thickness, and the crack length. The major results are presented in the form of contour plots of the bulging factor as a function of two nondimensional parameters: the shell curvature parameter, lambda, which is a function of the shell geometry, Poisson's ratio, and the crack length; and a loading parameter, eta, which is a function of the shell geometry, material properties, and the applied internal pressure. These plots identify the ranges of the shell curvature and loading parameters for which the effects of geometric nonlinearity are significant. Simple empirical expressions for the bulging factor are then derived from the numerical results and shown to predict accurately the nonlinear response of shells with longitudinal and circumferential cracks. The numerical results are also compared with analytical solutions based on linear shallow shell theory for thin shells, and with some other semi-empirical solutions from the literature, and limitations on the use of these other expressions are suggested.

Identification of transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) as a novel factor for TNF-α expression upon lipopolysaccharide stimulation in human monocytes.

PubMed

Murata, H; Hattori, T; Maeda, H; Takashiba, S; Takigawa, M; Kido, J; Nagata, T

2015-08-01

Tumor necrosis factor alpha (TNF-α) is a major cytokine implicated in various inflammatory diseases. The nature of the nuclear factors associated with human TNF-α gene regulation is not well elucidated. We previously identified a novel region located from -550 to -487 in human TNF-α promoter that did not contain the reported binding sites for nuclear factor kappa B (NF-κB) but showed lipopolysaccharide (LPS)-induced transcriptional activity. The purpose of this study is to identify novel factors that bind to the promoter region and regulate TNF-α expression. To identify DNA-binding proteins that bound to the target region of TNF-α promoter, a cDNA library from LPS-stimulated human monocytic cell line THP-1 was screened using a yeast one-hybrid system. Cellular localizations of the DNA-binding protein in the cells were examined by subcellular immunocytochemistry. Nuclear amounts of the protein in LPS-stimulated THP-1 cells were identified by western blot analysis. Expression of mRNA of the protein in the cells was quantified by real-time polymerase chain reaction. Electrophoretic mobility shift assays were performed to confirm the DNA-binding profile. Overexpression of the protein and knockdown of the gene were also performed to investigate the role for TNF-α expression. Several candidates were identified from the cDNA library and transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) was focused on. Western blot analysis revealed that nuclear TDP-43 protein was increased in the LPS-stimulated THP-1 cells. Expression of TDP-43 mRNA was already enhanced before TNF-α induction by LPS. Electrophoretic mobility shift assay analysis showed that nuclear extracts obtained by overexpressing FLAG-tagged TDP-43 bound to the -550 to -487 TNF-α promoter fragments. Overexpression of TDP-43 in THP-1 cells resulted in an increase of TNF-α expression. Knockdown of TDP-43 in THP-1 cells downregulated TNF-α expression. We identified TDP-43 as one of the novel

Factors Affecting Educational Innovation with in Class Electronic Response Systems

ERIC Educational Resources Information Center

Freeman, Mark; Bell, Amani; Comerton-Forde, Carole; Pickering, Joanne; Blayney, Paul

2007-01-01

This paper reports the use of Rogers' diffusion of innovation perspective to understand the factors affecting educational innovation decisions, specifically in regard to in class electronic response systems. Despite decreasing costs and four decades of research showing strong student support, academic adoption is limited. Using data collected from…

Expression of a transmembrane phosphotyrosine phosphatase inhibits cellular response to platelet-derived growth factor and insulin-like growth factor-1.

PubMed

Mooney, R A; Freund, G G; Way, B A; Bordwell, K L

1992-11-25

Tyrosine phosphorylation is a mechanism of signal transduction shared by many growth factor receptors and oncogene products. Phosphotyrosine phosphatases (PTPases) potentially modulate or counter-regulate these signaling pathways. To test this hypothesis, the transmembrane PTPase CD45 (leukocyte common antigen) was expressed in the murine cell line C127. Hormone-dependent autophosphorylation of the platelet-derived growth factor (PDGF) and insulin-like growth factor-1 (IGF-1) receptors was markedly reduced in cells expressing the transmembrane PTPase. Tyrosine phosphorylation of other PDGF-dependent phosphoproteins (160, 140, and 55 kDa) and IGF-1-dependent phosphoproteins (145 kDa) was similarly decreased. Interestingly, the pattern of growth factor-independent tyrosine phosphorylations was comparable in cells expressing the PTPase and control cells. This suggests a selectivity or accessibility of the PTPase limited to a subset of cellular phosphotyrosyl proteins. The maximum mitogenic response to PDGF and IGF-1 in cells expressing the PTPase was decreased by 67 and 71%, respectively. These results demonstrate that a transmembrane PTPase can both affect the tyrosine phosphorylation state of growth factor receptors and modulate proximal and distal cellular responses to the growth factors.

Identifying sex-specific risk factors for low bone mineral density in adolescent runners.

PubMed

Tenforde, Adam Sebastian; Fredericson, Michael; Sayres, Lauren Carter; Cutti, Phil; Sainani, Kristin Lynn

2015-06-01

Adolescent runners may be at risk for low bone mineral density (BMD) associated with sports participation. Few prior investigations have evaluated bone health in young runners, particularly males. To characterize sex-specific risk factors for low BMD in adolescent runners. Cross-sectional study; Level of evidence, 3. Training characteristics, fracture history, eating behaviors and attitudes, and menstrual history were measured using online questionnaires. A food frequency questionnaire was used to identify dietary patterns and measure calcium intake. Runners (female: n = 94, male: n = 42) completed dual-energy x-ray absorptiometry (DXA) to measure lumbar spine (LS) and total body less head (TBLH) BMD and body composition values, including android-to-gynoid (A:G) fat mass ratio. The BMD was standardized to Z-scores using age, sex, and race/ethnicity reference values. Questionnaire values were combined with DXA values to determine risk factors associated with differences in BMD Z-scores in LS and TBLH and low bone mass (defined as BMD Z-score ≤-1). In multivariable analyses, risk factors for lower LS BMD Z-scores in girls included lower A:G ratio, being shorter, and the combination of (interaction between) current menstrual irregularity and a history of fracture (all P < .01). Later age of menarche, lower A:G ratio, lower lean mass, and drinking less milk were associated with lower TBLH BMD Z-scores (P < .01). In boys, lower body mass index (BMI) Z-scores and the belief that being thinner improves performance were associated with lower LS and TBLH BMD Z-scores (all P < .05); lower A:G ratio was additionally associated with lower TBLH Z-scores (P < .01). Thirteen girls (14%) and 9 boys (21%) had low bone mass. Girls with a BMI ≤17.5 kg/m(2) or both menstrual irregularity and a history of fracture were significantly more likely to have low bone mass. Boys with a BMI ≤17.5 kg/m(2) and belief that thinness improves performance were significantly more likely to have

Genetic analysis of Physcomitrella patens identifies ABSCISIC ACID NON-RESPONSIVE, a regulator of ABA responses unique to basal land plants and required for desiccation tolerance

DOE PAGES

Stevenson, Sean Ross; Kamisugi, Yasuko; Trinh, Chi H.; ...

2016-05-18

The anatomically simple plants that first colonized land must have acquired molecular and biochemical adaptations to drought stress. Abscisic acid (ABA) coordinates responses leading to desiccation tolerance in all land plants. We identified ABA nonresponsive mutants in the model bryophyte Physcomitrella patens and genotyped a segregating population to map and identify the ABA NON-RESPONSIVE (ANR) gene encoding a modular protein kinase comprising an N-terminal PAS domain, a central EDR domain, and a C-terminal MAPKKK-like domain. anr mutants fail to accumulate dehydration tolerance-associated gene products in response to drought, ABA, or osmotic stress and do not acquire ABA-dependent desiccation tolerance. Themore » crystal structure of the PAS domain, determined to 1.7-Å resolution, shows a conserved PAS-fold that dimerizes through a weak dimerization interface. Targeted mutagenesis of a conserved tryptophan residue within the PAS domain generates plants with ABA nonresponsive growth and strongly attenuated ABA-responsive gene expression, whereas deleting this domain retains a fully ABA-responsive phenotype. ANR orthologs are found in early-diverging land plant lineages and aquatic algae but are absent from more recently diverged vascular plants. Lastly, we propose that ANR genes represent an ancestral adaptation that enabled drought stress survival of the first terrestrial colonizers but were lost during land plant evolution.« less

Genetic analysis of Physcomitrella patens identifies ABSCISIC ACID NON-RESPONSIVE, a regulator of ABA responses unique to basal land plants and required for desiccation tolerance

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

Stevenson, Sean Ross; Kamisugi, Yasuko; Trinh, Chi H.

The anatomically simple plants that first colonized land must have acquired molecular and biochemical adaptations to drought stress. Abscisic acid (ABA) coordinates responses leading to desiccation tolerance in all land plants. We identified ABA nonresponsive mutants in the model bryophyte Physcomitrella patens and genotyped a segregating population to map and identify the ABA NON-RESPONSIVE (ANR) gene encoding a modular protein kinase comprising an N-terminal PAS domain, a central EDR domain, and a C-terminal MAPKKK-like domain. anr mutants fail to accumulate dehydration tolerance-associated gene products in response to drought, ABA, or osmotic stress and do not acquire ABA-dependent desiccation tolerance. Themore » crystal structure of the PAS domain, determined to 1.7-Å resolution, shows a conserved PAS-fold that dimerizes through a weak dimerization interface. Targeted mutagenesis of a conserved tryptophan residue within the PAS domain generates plants with ABA nonresponsive growth and strongly attenuated ABA-responsive gene expression, whereas deleting this domain retains a fully ABA-responsive phenotype. ANR orthologs are found in early-diverging land plant lineages and aquatic algae but are absent from more recently diverged vascular plants. Lastly, we propose that ANR genes represent an ancestral adaptation that enabled drought stress survival of the first terrestrial colonizers but were lost during land plant evolution.« less

Improved system identification using artificial neural networks and analysis of individual differences in responses of an identified neuron.

PubMed

Costalago Meruelo, Alicia; Simpson, David M; Veres, Sandor M; Newland, Philip L

2016-03-01

Mathematical modelling is used routinely to understand the coding properties and dynamics of responses of neurons and neural networks. Here we analyse the effectiveness of Artificial Neural Networks (ANNs) as a modelling tool for motor neuron responses. We used ANNs to model the synaptic responses of an identified motor neuron, the fast extensor motor neuron, of the desert locust in response to displacement of a sensory organ, the femoral chordotonal organ, which monitors movements of the tibia relative to the femur of the leg. The aim of the study was threefold: first to determine the potential value of ANNs as tools to model and investigate neural networks, second to understand the generalisation properties of ANNs across individuals and to different input signals and third, to understand individual differences in responses of an identified neuron. A metaheuristic algorithm was developed to design the ANN architectures. The performance of the models generated by the ANNs was compared with those generated through previous mathematical models of the same neuron. The results suggest that ANNs are significantly better than LNL and Wiener models in predicting specific neural responses to Gaussian White Noise, but not significantly different when tested with sinusoidal inputs. They are also able to predict responses of the same neuron in different individuals irrespective of which animal was used to develop the model, although notable differences between some individuals were evident. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dehydration responsive element binding transcription factors and their applications for the engineering of stress tolerance.

PubMed

Agarwal, Pradeep K; Gupta, Kapil; Lopato, Sergiy; Agarwal, Parinita

2017-04-01

Dehydration responsive element binding (DREB) factors or CRT element binding factors (CBFs) are members of the AP2/ERF family, which comprises a large number of stress-responsive regulatory genes. This review traverses almost two decades of research, from the discovery of DREB/CBF factors to their optimization for application in plant biotechnology. In this review, we describe (i) the discovery, classification, structure, and evolution of DREB genes and proteins; (ii) induction of DREB genes by abiotic stresses and involvement of their products in stress responses; (iii) protein structure and DNA binding selectivity of different groups of DREB proteins; (iv) post-transcriptional and post-translational mechanisms of DREB transcription factor (TF) regulation; and (v) physical and/or functional interaction of DREB TFs with other proteins during plant stress responses. We also discuss existing issues in applications of DREB TFs for engineering of enhanced stress tolerance and improved performance under stress of transgenic crop plants. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Connexin43 Potentiates Osteoblast Responsiveness to Fibroblast Growth Factor 2 via a Protein Kinase C-Delta/Runx2–dependent Mechanism

PubMed Central

Lima, Florence; Niger, Corinne; Hebert, Carla

2009-01-01

In this study, we examine the role of the gap junction protein, connexin43 (Cx43), in the transcriptional response of osteocalcin to fibroblast growth factor 2 (FGF2) in MC3T3 osteoblasts. By luciferase reporter assays, we identify that the osteocalcin transcriptional response to FGF2 is markedly increased by overexpression of Cx43, an effect that is mediated by Runx2 via its OSE2 cognate element, but not by a previously identified connexin-responsive Sp1/Sp3-binding element. Furthermore, disruption of Cx43 function with Cx43 siRNAs or overexpression of connexin45 markedly attenuates the response to FGF2. Inhibition of protein kinase C delta (PKCδ) with rottlerin or siRNA-mediated knockdown abrogates the osteocalcin response to FGF2. Additionally, we show that upon treatment with FGF2, PKCδ translocates to the nucleus, PKCδ and Runx2 are phosphorylated and these events are enhanced by Cx43 overexpression, suggesting that the degree of activation is enhanced by increased Cx43 levels. Indeed, chromatin immunoprecipitations of the osteocalcin proximal promoter with antibodies against Runx2 demonstrate that the recruitment of Runx2 to the osteocalcin promoter in response to FGF2 treatment is dramatically enhanced by Cx43 overexpression. Thus, Cx43 plays a critical role in regulating the ability of osteoblasts to respond to FGF2 by impacting PKCδ and Runx2 function. PMID:19339281

Highly identified power-holders feel responsible: The interplay between social identification and social power within groups.

PubMed

Scholl, Annika; Sassenberg, Kai; Ellemers, Naomi; Scheepers, Daan; de Wit, Frank

2018-01-01

Power relations affect dynamics within groups. Power-holders' decisions not only determine their personal outcomes, but also the outcomes of others in the group that they control. Yet, power-holders often tend to overlook this responsibility to take care of collective interests. The present research investigated how social identification - with the group to which both the powerful and the powerless belong - alters perceived responsibility among power-holders (and the powerless). Combining research on social power and social identity, we argue that power-holders perceive more responsibility than the powerless when strongly (rather than when weakly) identifying with the group. A study among leaders and an experiment supported this, highlighting that although power-holders are often primarily concerned about personal outcomes, they do feel responsible for considering others' interests when these others are included in the (social) self. © 2017 The British Psychological Society.

Allelic variants of OsSUB1A cause differential expression of transcription factor genes in response to submergence in rice.

PubMed

Sharma, Niharika; Dang, Trang Minh; Singh, Namrata; Ruzicic, Slobodan; Mueller-Roeber, Bernd; Baumann, Ute; Heuer, Sigrid

2018-01-08

Flooding during seasonal monsoons affects millions of hectares of rice-cultivated areas across Asia. Submerged rice plants die within a week due to lack of oxygen, light and excessive elongation growth to escape the water. Submergence tolerance was first reported in an aus-type rice landrace, FR13A, and the ethylene-responsive transcription factor (TF) gene SUB1A-1 was identified as the major tolerance gene. Intolerant rice varieties generally lack the SUB1A gene but some intermediate tolerant varieties, such as IR64, carry the allelic variant SUB1A-2. Differential effects of the two alleles have so far not been addressed. As a first step, we have therefore quantified and compared the expression of nearly 2500 rice TF genes between IR64 and its derived tolerant near isogenic line IR64-Sub1, which carries the SUB1A-1 allele. Gene expression was studied in internodes, where the main difference in expression between the two alleles was previously shown. Nineteen and twenty-six TF genes were identified that responded to submergence in IR64 and IR64-Sub1, respectively. Only one gene was found to be submergence-responsive in both, suggesting different regulatory pathways under submergence in the two genotypes. These differentially expressed genes (DEGs) mainly included MYB, NAC, TIFY and Zn-finger TFs, and most genes were downregulated upon submergence. In IR64, but not in IR64-Sub1, SUB1B and SUB1C, which are also present in the Sub1 locus, were identified as submergence responsive. Four TFs were not submergence responsive but exhibited constitutive, genotype-specific differential expression. Most of the identified submergence responsive DEGs are associated with regulatory hormonal pathways, i.e. gibberellins (GA), abscisic acid (ABA), and jasmonic acid (JA), apart from ethylene. An in-silico promoter analysis of the two genotypes revealed the presence of allele-specific single nucleotide polymorphisms, giving rise to ABRE, DRE/CRT, CARE and Site II cis-elements, which

Modeling silicon diode energy response factors for use in therapeutic photon beams.

PubMed

Eklund, Karin; Ahnesjö, Anders

2009-10-21

Silicon diodes have good spatial resolution, which makes them advantageous over ionization chambers for dosimetry in fields with high dose gradients. However, silicon diodes overrespond to low-energy photons, that are more abundant in scatter which increase with large fields and larger depths. We present a cavity-theory-based model for a general response function for silicon detectors at arbitrary positions within photon fields. The model uses photon and electron spectra calculated from fluence pencil kernels. The incident photons are treated according to their energy through a bipartition of the primary beam photon spectrum into low- and high-energy components. Primary electrons from the high-energy component are treated according to Spencer-Attix cavity theory. Low-energy primary photons together with all scattered photons are treated according to large cavity theory supplemented with an energy-dependent factor K(E) to compensate for energy variations in the electron equilibrium. The depth variation of the response for an unshielded silicon detector has been calculated for 5 x 5 cm(2), 10 x 10 cm(2) and 20 x 20 cm(2) fields in 6 and 15 MV beams and compared with measurements showing that our model calculates response factors with deviations less than 0.6%. An alternative method is also proposed, where we show that one can use a correlation with the scatter factor to determine the detector response of silicon diodes with an error of less than 3% in 6 MV and 15 MV photon beams.

Validating the Copenhagen Psychosocial Questionnaire (COPSOQ-II) Using Set-ESEM: Identifying Psychosocial Risk Factors in a Sample of School Principals

PubMed Central

Dicke, Theresa; Marsh, Herbert W.; Riley, Philip; Parker, Philip D.; Guo, Jiesi; Horwood, Marcus

2018-01-01

School principals world-wide report high levels of strain and attrition resulting in a shortage of qualified principals. It is thus crucial to identify psychosocial risk factors that reflect principals' occupational wellbeing. For this purpose, we used the Copenhagen Psychosocial Questionnaire (COPSOQ-II), a widely used self-report measure covering multiple psychosocial factors identified by leading occupational stress theories. We evaluated the COPSOQ-II regarding factor structure and longitudinal, discriminant, and convergent validity using latent structural equation modeling in a large sample of Australian school principals (N = 2,049). Results reveal that confirmatory factor analysis produced marginally acceptable model fit. A novel approach we call set exploratory structural equation modeling (set-ESEM), where cross-loadings were only allowed within a priori defined sets of factors, fit well, and was more parsimonious than a full ESEM. Further multitrait-multimethod models based on the set-ESEM confirm the importance of a principal's psychosocial risk factors; Stressors and depression were related to demands and ill-being, while confidence and autonomy were related to wellbeing. We also show that working in the private sector was beneficial for showing a low psychosocial risk, while other demographics have little effects. Finally, we identify five latent risk profiles (high risk to no risk) of school principals based on all psychosocial factors. Overall the research presented here closes the theory application gap of a strong multi-dimensional measure of psychosocial risk-factors. PMID:29760670

Validating the Copenhagen Psychosocial Questionnaire (COPSOQ-II) Using Set-ESEM: Identifying Psychosocial Risk Factors in a Sample of School Principals.

PubMed

Dicke, Theresa; Marsh, Herbert W; Riley, Philip; Parker, Philip D; Guo, Jiesi; Horwood, Marcus

2018-01-01

School principals world-wide report high levels of strain and attrition resulting in a shortage of qualified principals. It is thus crucial to identify psychosocial risk factors that reflect principals' occupational wellbeing. For this purpose, we used the Copenhagen Psychosocial Questionnaire (COPSOQ-II), a widely used self-report measure covering multiple psychosocial factors identified by leading occupational stress theories. We evaluated the COPSOQ-II regarding factor structure and longitudinal, discriminant, and convergent validity using latent structural equation modeling in a large sample of Australian school principals ( N = 2,049). Results reveal that confirmatory factor analysis produced marginally acceptable model fit. A novel approach we call set exploratory structural equation modeling (set-ESEM), where cross-loadings were only allowed within a priori defined sets of factors, fit well, and was more parsimonious than a full ESEM. Further multitrait-multimethod models based on the set-ESEM confirm the importance of a principal's psychosocial risk factors; Stressors and depression were related to demands and ill-being, while confidence and autonomy were related to wellbeing. We also show that working in the private sector was beneficial for showing a low psychosocial risk, while other demographics have little effects. Finally, we identify five latent risk profiles (high risk to no risk) of school principals based on all psychosocial factors. Overall the research presented here closes the theory application gap of a strong multi-dimensional measure of psychosocial risk-factors.

Raman spectroscopy identifies radiation response in human non-small cell lung cancer xenografts

NASA Astrophysics Data System (ADS)

Harder, Samantha J.; Isabelle, Martin; Devorkin, Lindsay; Smazynski, Julian; Beckham, Wayne; Brolo, Alexandre G.; Lum, Julian J.; Jirasek, Andrew

2016-02-01

External beam radiation therapy is a standard form of treatment for numerous cancers. Despite this, there are no approved methods to account for patient specific radiation sensitivity. In this report, Raman spectroscopy (RS) was used to identify radiation-induced biochemical changes in human non-small cell lung cancer xenografts. Chemometric analysis revealed unique radiation-related Raman signatures that were specific to nucleic acid, lipid, protein and carbohydrate spectral features. Among these changes was a dramatic shift in the accumulation of glycogen spectral bands for doses of 5 or 15 Gy when compared to unirradiated tumours. When spatial mapping was applied in this analysis there was considerable variability as we found substantial intra- and inter-tumour heterogeneity in the distribution of glycogen and other RS spectral features. Collectively, these data provide unique insight into the biochemical response of tumours, irradiated in vivo, and demonstrate the utility of RS for detecting distinct radiobiological responses in human tumour xenografts.

SigTree: A Microbial Community Analysis Tool to Identify and Visualize Significantly Responsive Branches in a Phylogenetic Tree.

PubMed

Stevens, John R; Jones, Todd R; Lefevre, Michael; Ganesan, Balasubramanian; Weimer, Bart C

2017-01-01

Microbial community analysis experiments to assess the effect of a treatment intervention (or environmental change) on the relative abundance levels of multiple related microbial species (or operational taxonomic units) simultaneously using high throughput genomics are becoming increasingly common. Within the framework of the evolutionary phylogeny of all species considered in the experiment, this translates to a statistical need to identify the phylogenetic branches that exhibit a significant consensus response (in terms of operational taxonomic unit abundance) to the intervention. We present the R software package SigTree , a collection of flexible tools that make use of meta-analysis methods and regular expressions to identify and visualize significantly responsive branches in a phylogenetic tree, while appropriately adjusting for multiple comparisons.

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

Pleiotrophin, a multifunctional cytokine and growth factor, induces leukocyte responses through the integrin Mac-1.

PubMed

Shen, Di; Podolnikova, Nataly P; Yakubenko, Valentin P; Ardell, Christopher L; Balabiyev, Arnat; Ugarova, Tatiana P; Wang, Xu

2017-11-17

Pleiotrophin (PTN) is a multifunctional, cationic, glycosaminoglycan-binding cytokine and growth factor involved in numerous physiological and pathological processes, including tissue repair and inflammation-related diseases. PTN has been shown to promote leukocyte responses by inducing their migration and expression of inflammatory cytokines. However, the mechanisms through which PTN mediates these responses remain unclear. Here, we identified the integrin Mac-1 (αMβ2, CD11b/CD18) as the receptor mediating macrophage adhesion and migration to PTN. We also found that expression of Mac-1 on the surface of human embryonic kidney (HEK) 293 cells induced their adhesion and migration to PTN. Accordingly, PTN promoted Mac-1-dependent cell spreading and initiated intracellular signaling manifested in phosphorylation of Erk1/2. While binding to PTN, Mac-1 on Mac-1-expressing HEK293 cells appears to cooperate with cell-surface proteoglycans because both anti-Mac-1 function-blocking mAb and heparin were required to block adhesion. Moreover, biolayer interferometry and NMR indicated a direct interaction between the α M I domain, the major ligand-binding region of Mac-1, and PTN. Using peptide libraries, we found that in PTN the α M I domain bound sequences enriched in basic and hydrophobic residues, indicating that PTN conforms to the general principle of ligand-recognition specificity of the α M I domain toward cationic proteins/peptides. Finally, using recombinant PTN-derived fragments, we show that PTN contains two distinct Mac-1-binding sites in each of its constitutive domains. Collectively, these results identify PTN as a ligand for the integrin Mac-1 on the surface of leukocytes and suggest that this interaction may play a role in inflammatory responses. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Identification of the cAMP response element that controls transcriptional activation of the insulin-like growth factor-I gene by prostaglandin E2 in osteoblasts

NASA Technical Reports Server (NTRS)

Thomas, M. J.; Umayahara, Y.; Shu, H.; Centrella, M.; Rotwein, P.; McCarthy, T. L.

1996-01-01

Insulin-like growth factor-I (IGF-I), a multifunctional growth factor, plays a key role in skeletal growth and can enhance bone cell replication and differentiation. We previously showed that prostaglandin E2 (PGE2) and other agents that increase cAMP activated IGF-I gene transcription in primary rat osteoblast cultures through promoter 1 (P1), the major IGF-I promoter, and found that transcriptional induction was mediated by protein kinase A. We now have identified a short segment of P1 that is essential for full hormonal regulation and have characterized inducible DNA-protein interactions involving this site. Transient transfections of IGF-I P1 reporter genes into primary rat osteoblasts showed that the 328-base pair untranslated region of exon 1 was required for a full 5.3-fold response to PGE2; mutation in a previously footprinted site, HS3D (base pairs +193 to +215), reduced induction by 65%. PGE2 stimulated nuclear protein binding to HS3D. Binding, as determined by gel mobility shift assay, was not seen in nuclear extracts from untreated osteoblast cultures, was detected within 2 h of PGE2 treatment, and was maximal by 4 h. This DNA-protein interaction was not observed in cytoplasmic extracts from PGE2-treated cultures, indicating nuclear localization of the protein kinase A-activated factor(s). Activation of this factor was not blocked by cycloheximide (Chx), and Chx did not impair stimulation of IGF-I gene expression by PGE2. In contrast, binding to a consensus cAMP response element (CRE; 5'-TGACGTCA-3') from the rat somatostatin gene was not modulated by PGE2 or Chx. Competition gel mobility shift analysis using mutated DNA probes identified 5'-CGCAATCG-3' as the minimal sequence needed for inducible binding. All modified IGF-I P1 promoterreporter genes with mutations within this CRE sequence also showed a diminished functional response to PGE2. These results identify the CRE within the 5'-untranslated region of IGF-I exon 1 that is required for hormonal

Chimeric tRNAs as tools to induce proteome damage and identify components of stress responses.

PubMed

Geslain, Renaud; Cubells, Laia; Bori-Sanz, Teresa; Alvarez-Medina, Roberto; Rossell, David; Martí, Elisa; Ribas de Pouplana, Lluís

2010-03-01

Misfolded proteins are caused by genomic mutations, aberrant splicing events, translation errors or environmental factors. The accumulation of misfolded proteins is a phenomenon connected to several human disorders, and is managed by stress responses specific to the cellular compartments being affected. In wild-type cells these mechanisms of stress response can be experimentally induced by expressing recombinant misfolded proteins or by incubating cells with large concentrations of amino acid analogues. Here, we report a novel approach for the induction of stress responses to protein aggregation. Our method is based on engineered transfer RNAs that can be expressed in cells or tissues, where they actively integrate in the translation machinery causing general proteome substitutions. This strategy allows for the introduction of mutations of increasing severity randomly in the proteome, without exposing cells to unnatural compounds. Here, we show that this approach can be used for the differential activation of the stress response in the Endoplasmic Reticulum (ER). As an example of the applications of this method, we have applied it to the identification of human microRNAs activated or repressed during unfolded protein stress.

The tomato mutant ars1 (altered response to salt stress 1) identifies an R1-type MYB transcription factor involved in stomatal closure under salt acclimation.

PubMed

Campos, Juan F; Cara, Beatriz; Pérez-Martín, Fernando; Pineda, Benito; Egea, Isabel; Flores, Francisco B; Fernandez-Garcia, Nieves; Capel, Juan; Moreno, Vicente; Angosto, Trinidad; Lozano, Rafael; Bolarin, Maria C

2016-06-01

A screening under salt stress conditions of a T-DNA mutant collection of tomato (Solanum lycopersicum L.) led to the identification of the altered response to salt stress 1 (ars1) mutant, which showed a salt-sensitive phenotype. Genetic analysis of the ars1 mutation revealed that a single T-DNA insertion in the ARS1 gene was responsible of the mutant phenotype. ARS1 coded for an R1-MYB type transcription factor and its expression was induced by salinity in leaves. The mutant reduced fruit yield under salt acclimation while in the absence of stress the disruption of ARS1 did not affect this agronomic trait. The stomatal behaviour of ars1 mutant leaves induced higher Na(+) accumulation via the transpiration stream, as the decreases of stomatal conductance and transpiration rate induced by salt stress were markedly lower in the mutant plants. Moreover, the mutation affected stomatal closure in a response mediated by abscisic acid (ABA). The characterization of tomato transgenic lines silencing and overexpressing ARS1 corroborates the role of the gene in regulating the water loss via transpiration under salinity. Together, our results show that ARS1 tomato gene contributes to reduce transpirational water loss under salt stress. Finally, this gene could be interesting for tomato molecular breeding, because its manipulation could lead to improved stress tolerance without yield penalty under optimal culture conditions. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

First Spanish version of the Memorial Delirium Assessment Scale: psychometric properties, responsiveness, and factor loadings.

PubMed

Noguera, Antonio; Carvajal, Ana; Alonso-Babarro, Alberto; Chisholm, Gary; Bruera, Eduardo; Centeno, Carlos

2014-01-01

The Memorial Delirium Assessment Scale (MDAS) is a reliable and validated instrument with which to assess delirium. However, MDAS responsiveness has only been investigated in an indirect way. Also, neurobehavioral and global cognitive factors seem to be the MDAS main factor loads. The primary objective of this study was to evaluate MDAS responsiveness and analyze individual factors on this scale. The secondary objective was to confirm concurrent validity and reliability of the Spanish version of the MDAS. The translation-back translation method was used to obtain the Spanish version of the MDAS. Delirium diagnosis was determined by the clinical Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria and with the Confusion Assessment Method. Responsiveness and factor loadings were determined with the Delirium Rating Scale-Revised-98, the Mini-Mental State Examination (MMSE), and the MDAS at baseline (0 hours) and at 72 hours. Variation in the scores of the Delirium Rating Scale-Revised-98 shows a correlation of r = 0.93, with variation in MDAS scores at P < 0.001. Variation in MMSE scores shows a correlation of r = -0.84, with variation in MDAS scores at P = 0.015. Factor I, neurobehavioral (reduced awareness, reduced attention, perceptual disturbance, delusions, altered psychomotor activity, and sleep-wake cycle disturbance), correlated moderately with the MMSE at -0.56. Factor II, global cognitive (disorientation, short-term memory impairment, impaired digit span, and disorganized thinking), correlated strongly with the MMSE at -0.81. Factor II was significantly more reliable than Factor I, rho = 0.7, P = 0.01. The high responsiveness confirms the value of the MDAS for ongoing delirium assessment. Two differentiated factor loadings point to a potential future need for MDAS subscales. Copyright © 2014 U.S. Cancer Pain Relief Committee. All rights reserved.

Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk Military Families and Civilian Families

DTIC Science & Technology

2016-08-01

Award Number: W81XWH-12-2-0034 TITLE: Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk...2. REPORT TYPE Final 3. DATES COVERED (From - To) 15May2012 - 31Aug2016 Identifying Military and Combat-Specific Risk Factors for Child Adjustment...deployment and has a child between the age of 3 and 7 and comparison groups of civilain single parent families (N=200) and civilian dual parent

Using Multi-Group Confirmatory Factor Analysis to Evaluate Cross-Cultural Research: Identifying and Understanding Non-Invariance

ERIC Educational Resources Information Center

Brown, Gavin T. L.; Harris, Lois R.; O'Quin, Chrissie; Lane, Kenneth E.

2017-01-01

Multi-group confirmatory factor analysis (MGCFA) allows researchers to determine whether a research inventory elicits similar response patterns across samples. If statistical equivalence in responding is found, then scale score comparisons become possible and samples can be said to be from the same population. This paper illustrates the use of…

Identifying the nonlinear mechanical behaviour of micro-speakers from their quasi-linear electrical response

NASA Astrophysics Data System (ADS)

Zilletti, Michele; Marker, Arthur; Elliott, Stephen John; Holland, Keith

2017-05-01

In this study model identification of the nonlinear dynamics of a micro-speaker is carried out by purely electrical measurements, avoiding any explicit vibration measurements. It is shown that a dynamic model of the micro-speaker, which takes into account the nonlinear damping characteristic of the device, can be identified by measuring the response between the voltage input and the current flowing into the coil. An analytical formulation of the quasi-linear model of the micro-speaker is first derived and an optimisation method is then used to identify a polynomial function which describes the mechanical damping behaviour of the micro-speaker. The analytical results of the quasi-linear model are compared with numerical results. This study potentially opens up the possibility of efficiently implementing nonlinear echo cancellers.

Estimation and Identifiability of Model Parameters in Human Nociceptive Processing Using Yes-No Detection Responses to Electrocutaneous Stimulation.

PubMed

Yang, Huan; Meijer, Hil G E; Buitenweg, Jan R; van Gils, Stephan A

2016-01-01

Healthy or pathological states of nociceptive subsystems determine different stimulus-response relations measured from quantitative sensory testing. In turn, stimulus-response measurements may be used to assess these states. In a recently developed computational model, six model parameters characterize activation of nerve endings and spinal neurons. However, both model nonlinearity and limited information in yes-no detection responses to electrocutaneous stimuli challenge to estimate model parameters. Here, we address the question whether and how one can overcome these difficulties for reliable parameter estimation. First, we fit the computational model to experimental stimulus-response pairs by maximizing the likelihood. To evaluate the balance between model fit and complexity, i.e., the number of model parameters, we evaluate the Bayesian Information Criterion. We find that the computational model is better than a conventional logistic model regarding the balance. Second, our theoretical analysis suggests to vary the pulse width among applied stimuli as a necessary condition to prevent structural non-identifiability. In addition, the numerically implemented profile likelihood approach reveals structural and practical non-identifiability. Our model-based approach with integration of psychophysical measurements can be useful for a reliable assessment of states of the nociceptive system.

Sex differences in stress responses: a critical role for corticotropin-releasing factor.

PubMed

Bangasser, Debra A; Wiersielis, Kimberly R

2018-03-01

Rates of post-traumatic stress disorder, panic disorder, and major depression are higher in women than in men. Another shared feature of these disorders is that dysregulation of the stress neuropeptide, corticotropin-releasing factor (CRF), is thought to contribute to their pathophysiology. Therefore, sex differences in responses to CRF could contribute to this sex bias in disease prevalence. Here, we review emerging data from non-human animal models that reveal extensive sex differences in CRF functions ranging from its presynaptic regulation to its postsynaptic efficacy. Specifically, detailed are sex differences in the regulation of CRF-containing neurons and the amount of CRF that they produce. We also describe sex differences in CRF receptor expression, distribution, trafficking, and signaling. Finally, we highlight sex differences in the processes that mitigate the effects of CRF. In most cases, the identified sex differences can lead to increased stress sensitivity in females. Thus, the relevance of these differences for the increased risk of depression and anxiety disorders in women compared to men is also discussed.

Using exploratory regression to identify optimal driving factors for cellular automaton modeling of land use change.

PubMed

Feng, Yongjiu; Tong, Xiaohua

2017-09-22

Defining transition rules is an important issue in cellular automaton (CA)-based land use modeling because these models incorporate highly correlated driving factors. Multicollinearity among correlated driving factors may produce negative effects that must be eliminated from the modeling. Using exploratory regression under pre-defined criteria, we identified all possible combinations of factors from the candidate factors affecting land use change. Three combinations that incorporate five driving factors meeting pre-defined criteria were assessed. With the selected combinations of factors, three logistic regression-based CA models were built to simulate dynamic land use change in Shanghai, China, from 2000 to 2015. For comparative purposes, a CA model with all candidate factors was also applied to simulate the land use change. Simulations using three CA models with multicollinearity eliminated performed better (with accuracy improvements about 3.6%) than the model incorporating all candidate factors. Our results showed that not all candidate factors are necessary for accurate CA modeling and the simulations were not sensitive to changes in statistically non-significant driving factors. We conclude that exploratory regression is an effective method to search for the optimal combinations of driving factors, leading to better land use change models that are devoid of multicollinearity. We suggest identification of dominant factors and elimination of multicollinearity before building land change models, making it possible to simulate more realistic outcomes.

Factors influencing identification of and response to intimate partner violence: a survey of physicians and nurses

PubMed Central

Gutmanis, Iris; Beynon, Charlene; Tutty, Leslie; Wathen, C Nadine; MacMillan, Harriet L

2007-01-01

Background Intimate partner violence against women (IPV) has been identified as a serious public health problem. Although the health care system is an important site for identification and intervention, there have been challenges in determining how health care professionals can best address this issue in practice. We surveyed nurses and physicians in 2004 regarding their attitudes and behaviours with respect to IPV, including whether they routinely inquire about IPV, as well as potentially relevant barriers, facilitators, experiential, and practice-related factors. Methods A modified Dillman Tailored Design approach was used to survey 1000 nurses and 1000 physicians by mail in Ontario, Canada. Respondents were randomly selected from professional directories and represented practice areas pre-identified from the literature as those most likely to care for women at the point of initial IPV disclosure: family practice, obstetrics and gynecology, emergency care, maternal/newborn care, and public health. The survey instrument had a case-based scenario followed by 43 questions asking about behaviours and resources specific to woman abuse. Results In total, 931 questionnaires were returned; 597 by nurses (59.7% response rate) and 328 by physicians (32.8% response rate). Overall, 32% of nurses and 42% of physicians reported routinely initiating the topic of IPV in practice. Principal components analysis identified eight constructs related to whether routine inquiry was conducted: preparedness, self-confidence, professional supports, abuse inquiry, practitioner consequences of asking, comfort following disclosure, practitioner lack of control, and practice pressures. Each construct was analyzed according to a number of related issues, including clinician training and experience with woman abuse, area of practice, and type of health care provider. Preparedness emerged as a key construct related to whether respondents routinely initiated the topic of IPV. Conclusion The

Ethylene-responsive element-binding factor 5, ERF5, is involved in chitin-induced innate immunity response.

PubMed

Son, Geon Hui; Wan, Jinrong; Kim, Hye Jin; Nguyen, Xuan Canh; Chung, Woo Sik; Hong, Jong Chan; Stacey, Gary

2012-01-01

Our recent work demonstrated that chitin treatment modulated the expression of 118 transcription factor (TF) genes in Arabidopsis. To investigate the potential roles of these TF in chitin signaling and plant defense, we initiated an interaction study among these TF proteins, as well as two chitin-activated mitogen-activated protein kinases (MPK3 and MPK6), using a yeast two-hybrid system. This study revealed interactions among the following proteins: three ethylene-responsive element-binding factors (ERF), five WRKY transcription factors, one scarecrow-like (SCL), and the two MPK, in addition to many other interactions, reflecting a complex TF interaction network. Most of these interactions were subsequently validated by other methods, such as pull-down and in planta bimolecular fluorescence complementation assays. The key node ERF5 was shown to interact with multiple proteins in the network, such as ERF6, ERF8, and SCL13, as well as MPK3 and MPK6. Interestingly, ERF5 appeared to negatively regulate chitin signaling and plant defense against the fungal pathogen Alternaria brassicicola and positively regulate salicylic acid signaling and plant defense against the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. Therefore, ERF5 may play an important role in plant innate immunity, likely through coordinating chitin and other defense pathways in plants in response to different pathogens.

Next-generation sequencing identifies deregulation of microRNAs involved in both innate and adaptive immune response in ALK+ ALCL.

PubMed

Steinhilber, Julia; Bonin, Michael; Walter, Michael; Fend, Falko; Bonzheim, Irina; Quintanilla-Martinez, Leticia

2015-01-01

Anaplastic large cell lymphoma (ALCL) is divided into two systemic diseases according to the expression of the anaplastic lymphoma kinase (ALK). We investigated the differential expression of miRNAs between ALK+ ALCL, ALK- ALCL cells and normal T-cells using next generation sequencing (NGS). In addition, a C/EBPβ-dependent miRNA profile was generated. The data were validated in primary ALCL cases. NGS identified 106 miRNAs significantly differentially expressed between ALK+ and ALK- ALCL and 228 between ALK+ ALCL and normal T-cells. We identified a signature of 56 miRNAs distinguishing ALK+ ALCL, ALK- ALCL and T-cells. The top candidates significant differentially expressed between ALK+ and ALK- ALCL included 5 upregulated miRNAs: miR-340, miR-203, miR-135b, miR-182, miR-183; and 7 downregulated: miR-196b, miR-155, miR-146a, miR-424, miR-503, miR-424*, miR-542-3p. The miR-17-92 cluster was also upregulated in ALK+ cells. Additionally, we identified a signature of 3 miRNAs significantly regulated by the transcription factor C/EBPβ, which is specifically overexpressed in ALK+ ALCL, including the miR-181 family. Of interest, miR-181a, which regulates T-cell differentiation and modulates TCR signalling strength, was significantly downregulated in ALK+ ALCL cases. In summary, our data reveal a miRNA signature linking ALK+ ALCL to a deregulated immune response and may reflect the abnormal TCR antigen expression known in ALK+ ALCL.

Lung-cancer mortality among Vermont granite workers: factors influencing exposure–response evaluation

PubMed Central

Vacek, Pamela M; Callas, Peter W

2017-01-01

Objective To understand why 2 studies relating crystalline silica exposure to lung-cancer mortality in Vermont granite workers yielded conflicting results. Methods Data used in the 2 studies were linked to identify discrepancies. Mortality data and employment histories from the earlier study were revised based on data obtained in the later study. SMR were computed and Poisson regressions corresponding to those in the earlier study were performed using the original and revised data. Analyses were repeated with the addition of workers omitted from the earlier study. Results After correction of incomplete mortality and employment information in the original data, the overall SMR for the cohort in the earlier study increased from 1.17 (95% CI 1.03 to 1.36) to 1.39 (95% CI 1.22 to 1.59), and was similar to the SMR of 1.37 observed in the later study (95% CI 1.23 to 1.52). The exposure–response relationship was attenuated, particularly when person-years in all exposure categories were included in the analysis. Inclusion of additional workers had a smaller impact on the SMRs but further attenuated the exposure–response relationship. Conclusions Differing results from the 2 studies are partly attributable to incomplete vital status and work history information used in the earlier study, as well as differences in cohort inclusion criteria. However, differences in length of follow-up and other factors likely play a larger role. PMID:27821675

Systems and Trans-System Level Analysis Identifies Conserved Iron Deficiency Responses in the Plant Lineage[W][OA

PubMed Central

Urzica, Eugen I.; Casero, David; Yamasaki, Hiroaki; Hsieh, Scott I.; Adler, Lital N.; Karpowicz, Steven J.; Blaby-Haas, Crysten E.; Clarke, Steven G.; Loo, Joseph A.; Pellegrini, Matteo; Merchant, Sabeeha S.

2012-01-01

We surveyed the iron nutrition-responsive transcriptome of Chlamydomonas reinhardtii using RNA-Seq methodology. Presumed primary targets were identified in comparisons between visually asymptomatic iron-deficient versus iron-replete cells. This includes the known components of high-affinity iron uptake as well as candidates for distributive iron transport in C. reinhardtii. Comparison of growth-inhibited iron-limited versus iron-replete cells revealed changes in the expression of genes in chloroplastic oxidative stress response pathways, among hundreds of other genes. The output from the transcriptome was validated at multiple levels: by quantitative RT-PCR for assessing the data analysis pipeline, by quantitative proteomics for assessing the impact of changes in RNA abundance on the proteome, and by cross-species comparison for identifying conserved or universal response pathways. In addition, we assessed the functional importance of three target genes, VITAMIN C 2 (VTC2), MONODEHYDROASCORBATE REDUCTASE 1 (MDAR1), and CONSERVED IN THE GREEN LINEAGE AND DIATOMS 27 (CGLD27), by biochemistry or reverse genetics. VTC2 and MDAR1, which are key enzymes in de novo ascorbate synthesis and ascorbate recycling, respectively, are likely responsible for the 10-fold increase in ascorbate content of iron-limited cells. CGLD27/At5g67370 is a highly conserved, presumed chloroplast-localized pioneer protein and is important for growth of Arabidopsis thaliana in low iron. PMID:23043051

Extremity movements help occupational therapists identify stress responses in preterm infants in the neonatal intensive care unit: a systematic review.

PubMed

Holsti, Liisa; Grunau, Ruth E

2007-06-01

Accurate assessment and treatment of pain and stress in preterm infants in neonatal intensive care units (NICU) is vital because pain and stress responses have been linked to long-term alterations in development in this population. To review the evidence of specific extremity movements in preterm infants as observed during stressful procedures. Five on-line databases were searched for relevant studies. For each study, levels of evidence were determined and effect size estimates were calculated. Each study was also evaluated for specific factors that presented potential threats to its validity. Eighteen studies were identified and seven comprised the review. The combined sample included 359 preterm infants. Six specific movements were associated with painful and intrusive procedures. A set of specific extremity movements, when combined with other reliable biobehavioural measures of pain and stress, can form the basis for future research and development of a clinical stress scale for preterm infants.

IDENTIFYING ELEVEN FACTORS OF SERVICE MARKETING MIX (4PS) EFFECTIVE ON TENDENCY OF PATIENTS TOWARD PRIVATE HOSPITAL.

PubMed

Hosseini, Seyed Mojtaba; Etesaminia, Samira; Jafari, Mehrnoosh

2016-10-01

One of the important factors of correct management is to identify the reasons for patient tendency toward private hospitals. This study measures these factors based on service marketing mixes. This study used a cross sectional descriptive methodology. The study was conducted during 6 months in 2015. The studied population included patients of private hospitals in Tehran. Random sampling was used (n = 200). Data was collected by an author-made questionnaire for service marketing factors. Reliability and validity of the questionnaire were confirmed. Data analysis was done using factor analysis test in SPSS 20. The results showed that constant attendance of physicians and nurses has the highest effect (0.707%) on patient tendency toward private hospitals.

Identifying Military and Combat Specific Risk Factors for Child Adjustment: Comparing High and Low Risk Military Families and Civilian Families

DTIC Science & Technology

2016-06-01

Award Number: W81XWH-12-2-0034 TITLE: Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk...2. REPORT TYPE Annual 3. DATES COVERED (From - To) 15 May - 2013 - 14 May 2014. Identifying Military and Combat-Specific Risk Factors for Child ...parents (N=200) whose spouse/partner is currently in a “low perceived risk” deployment and has a child between the age of 3 and 7 and comparison

Exaggerated blood pressure response during exercise treadmill testing: functional and hemodynamic features, and risk factors.

PubMed

de Lima, Sandro G; de Albuquerque, Maria de F P M; de Oliveira, João R M; Ayres, Constância F J; da Cunha, José E G; de Oliveira, Danyllo F; de Lemos, Roberta R; de Souza, Manuela B R; e Silva, Odwaldo B

2012-07-01

The factors which contribute to an exaggerated blood pressure response (EBPR) during the exercise treadmill test (ETT) are not wholly understood. The association between the insertion/deletion polymorphisms of the angiotensin-converting enzyme (ACE) and M235T of the angiotensinogen with EBPR during ETT still remains unstudied. To identify and compare the risk factors for hypertension between normotensive subjects with EBPR and those who exhibit a normal curve of blood pressure (BP) during ETT. In a series of EBPR cases from a historical cohort of normotensive individuals, a univariate analysis was performed to estimate the association of the studied factors with BP behavior during ETT. Additionally, logistic multivariate regression was conducted to analyze the joint effects of the variables. P-values above 0.05 were considered statistically significant. From a total of 10,027 analyzed examinations, only 219 met the criteria employed to define EBPR, which resulted in a prevalence of 12.6%. For the systolic component of the BP, hyperreactive subjects displayed a mean age and body mass index (BMI) significantly higher than the others (P=0.002 and <0.001, respectively). No association was observed between the polymorphisms cited above and EBPR. An analysis of the joint effect of variables has indicated that only age (P< 0.001) and BMI (P=0.001) were specifically associated with systolic BP during exercise. Age and BMI were the only factors that independently influenced EBPR during ETT.

Relating genes to function: identifying enriched transcription factors using the ENCODE ChIP-Seq significance tool.

PubMed

Auerbach, Raymond K; Chen, Bin; Butte, Atul J

2013-08-01

Biological analysis has shifted from identifying genes and transcripts to mapping these genes and transcripts to biological functions. The ENCODE Project has generated hundreds of ChIP-Seq experiments spanning multiple transcription factors and cell lines for public use, but tools for a biomedical scientist to analyze these data are either non-existent or tailored to narrow biological questions. We present the ENCODE ChIP-Seq Significance Tool, a flexible web application leveraging public ENCODE data to identify enriched transcription factors in a gene or transcript list for comparative analyses. The ENCODE ChIP-Seq Significance Tool is written in JavaScript on the client side and has been tested on Google Chrome, Apple Safari and Mozilla Firefox browsers. Server-side scripts are written in PHP and leverage R and a MySQL database. The tool is available at http://encodeqt.stanford.edu. abutte@stanford.edu Supplementary material is available at Bioinformatics online.

Critical role of the pore domain in the cold response of TRPM8 channels identified by ortholog functional comparison.

PubMed

Pertusa, María; Rivera, Bastián; González, Alejandro; Ugarte, Gonzalo; Madrid, Rodolfo

2018-06-07

In mammals, the main molecular entity involved in innocuous cold transduction is TRPM8.  This polymodal ion channel is activated by cold, cooling compounds such as menthol and voltage.  Despite its relevance, the molecular determinants involved in its activation by cold remain elusive.  In this study we explored the use of TRPM8 orthologs with different cold responses, as a strategy to identify new molecular determinants related with its thermosensitivity.  We focused on mouse TRPM8 (mTRPM8) and chicken TRPM8 (cTRPM8), which present complementary thermo- and chemo-sensitive phenotypes.  While mTRPM8 displays larger responses to cold than cTRPM8, the avian ortholog shows a higher sensitivity to menthol compared to the mouse channel, in both HEK293 cells and primary somatosensory neurons.  We took advantage of these differences to build multiple functional chimeras between these orthologs, in order to identify the regions that account for these discrepancies.  Using a combination of calcium imaging and patch clamping, we identified a region encompassing positions 526-556 in the N-terminus, whose replacement by the cTRPM8 homolog sequence potentiated its response to agonists.  More importantly, we found that the characteristic cold response of these orthologs is due to non-conserved residues located within the pore loop, suggesting that TRPM8 has evolved by increasing the magnitude of its cold response through changes in this region.  Our results reveal that these structural domains are critically involved in cold-sensitivity and functional modulation of TRPM8, and support the idea that the pore domain is a key molecular determinant in temperature responses of this thermo-TRP channel. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

A generalized linear factor model approach to the hierarchical framework for responses and response times.

PubMed

Molenaar, Dylan; Tuerlinckx, Francis; van der Maas, Han L J

2015-05-01

We show how the hierarchical model for responses and response times as developed by van der Linden (2007), Fox, Klein Entink, and van der Linden (2007), Klein Entink, Fox, and van der Linden (2009), and Glas and van der Linden (2010) can be simplified to a generalized linear factor model with only the mild restriction that there is no hierarchical model at the item side. This result is valuable as it enables all well-developed modelling tools and extensions that come with these methods. We show that the restriction we impose on the hierarchical model does not influence parameter recovery under realistic circumstances. In addition, we present two illustrative real data analyses to demonstrate the practical benefits of our approach. © 2014 The British Psychological Society.

OPTICAL COHERENCE TOMOGRAPHY BASELINE PREDICTORS FOR INITIAL BEST-CORRECTED VISUAL ACUITY RESPONSE TO INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN EYES WITH DIABETIC MACULAR EDEMA: The CHARTRES Study.

PubMed

Santos, Ana R; Costa, Miguel Â; Schwartz, Christian; Alves, Dalila; Figueira, João; Silva, Rufino; Cunha-Vaz, Jose G

2018-06-01

To identify baseline optical coherence tomography morphologic characteristics predicting the visual response to anti-vascular endothelial growth factor therapy in diabetic macular edema. Sixty-seven patients with diabetic macular edema completed a prospective, observational study (NCT01947881-CHARTRES). All patients received monthly intravitreal injections of Lucentis for 3 months followed by PRN treatment and underwent best-corrected visual acuity measurements and spectral domain optical coherence tomography at Baseline, Months 1, 2, 3, and 6. Visual treatment response was characterized as good (≥10 letters), moderate (5-10 letters), and poor (<5 or letters loss). Spectral domain optical coherence tomography images were graded before and after treatment by a certified Reading Center. One month after loading dose, 26 patients (38.80%) were identified as good responders, 19 (28.35%) as Moderate and 22 (32.83%) as poor responders. There were no significant best-corrected visual acuity and central retinal thickness differences at baseline (P = 0.176; P = 0.573, respectively). Ellipsoid zone disruption and disorganization of retinal inner layers were good predictors for treatment response, representing a significant risk for poor visual recovery to anti-vascular endothelial growth factor therapy (odds ratio = 10.96; P < 0.001 for ellipsoid zone disruption and odds ratio = 7.05; P = 0.034 for disorganization of retinal inner layers). Damage of ellipsoid zone, higher values of disorganization of retinal inner layers, and central retinal thickness decrease are good predictors of best-corrected visual acuity response to anti-vascular endothelial growth factor therapy.

Definition of a core module for the nuclear retrograde response to altered organellar gene expression identifies GLK overexpressors as gun mutants.

PubMed

Leister, Dario; Kleine, Tatjana

2016-07-01

Retrograde signaling can be triggered by changes in organellar gene expression (OGE) induced by inhibitors such as lincomycin (LIN) or mutations that perturb OGE. Thus, an insufficiency of the organelle-targeted prolyl-tRNA synthetase PRORS1 in Arabidopsis thaliana activates retrograde signaling and reduces the expression of nuclear genes for photosynthetic proteins. Recently, we showed that mTERF6, a member of the so-called mitochondrial transcription termination factor (mTERF) family, is involved in the formation of chloroplast (cp) isoleucine-tRNA. To obtain further insights into its functions, co-expression analysis of MTERF6, PRORS1 and two other genes for organellar aminoacyl-tRNA synthetases was conducted. The results suggest a prominent role of mTERF6 in aminoacylation activity, light signaling and seed storage. Analysis of changes in whole-genome transcriptomes in the mterf6-1 mutant showed that levels of nuclear transcripts for cp OGE proteins were particularly affected. Comparison of the mterf6-1 transcriptome with that of prors1-2 showed that reduced aminoacylation of proline (prors1-2) and isoleucine (mterf6-1) tRNAs alters retrograde signaling in similar ways. Database analyses indicate that comparable gene expression changes are provoked by treatment with LIN, norflurazon or high light. A core OGE response module was defined by identifying genes that were differentially expressed under at least four of six conditions relevant to OGE signaling. Based on this module, overexpressors of the Golden2-like transcription factors GLK1 and GLK2 were identified as genomes uncoupled mutants. © 2016 Scandinavian Plant Physiology Society.

Identifying anti-cancer drug response related genes using an integrative analysis of transcriptomic and genomic variations with cell line-based drug perturbations.

PubMed

Sun, Yi; Zhang, Wei; Chen, Yunqin; Ma, Qin; Wei, Jia; Liu, Qi

2016-02-23

Clinical responses to anti-cancer therapies often only benefit a defined subset of patients. Predicting the best treatment strategy hinges on our ability to effectively translate genomic data into actionable information on drug responses. To achieve this goal, we compiled a comprehensive collection of baseline cancer genome data and drug response information derived from a large panel of cancer cell lines. This data set was applied to identify the signature genes relevant to drug sensitivity and their resistance by integrating CNVs and the gene expression of cell lines with in vitro drug responses. We presented an efficient in-silico pipeline for integrating heterogeneous cell line data sources with the simultaneous modeling of drug response values across all the drugs and cell lines. Potential signature genes correlated with drug response (sensitive or resistant) in different cancer types were identified. Using signature genes, our collaborative filtering-based drug response prediction model outperformed the 44 algorithms submitted to the DREAM competition on breast cancer cells. The functions of the identified drug response related signature genes were carefully analyzed at the pathway level and the synthetic lethality level. Furthermore, we validated these signature genes by applying them to the classification of the different subtypes of the TCGA tumor samples, and further uncovered their in vivo implications using clinical patient data. Our work may have promise in translating genomic data into customized marker genes relevant to the response of specific drugs for a specific cancer type of individual patients.

Genomic and transcriptomic characterization of the transcription factor family R2R3-MYB in soybean and its involvement in the resistance responses to Phakopsora pachyrhizi.

PubMed

Aoyagi, Luciano N; Lopes-Caitar, Valéria S; de Carvalho, Mayra C C G; Darben, Luana M; Polizel-Podanosqui, Adriana; Kuwahara, Marcia K; Nepomuceno, Alexandre L; Abdelnoor, Ricardo V; Marcelino-Guimarães, Francismar C

2014-12-01

Myb genes constitute one of the largest transcription factor families in the plant kingdom. Soybean MYB transcription factors have been related to the plant response to biotic stresses. Their involvement in response to Phakopsora pachyrhizi infection has been reported by several transcriptional studies. Due to their apparently highly diverse functions, these genes are promising targets for developing crop varieties resistant to diseases. In the present study, the identification and phylogenetic analysis of the soybean R2R3-MYB (GmMYB) transcription factor family was performed and the expression profiles of these genes under biotic stress were determined. GmMYBs were identified from the soybean genome using bioinformatic tools, and their putative functions were determined based on the phylogenetic tree and classified into subfamilies using guides AtMYBs describing known functions. The transcriptional profiles of GmMYBs upon infection with different pathogen were revealed by in vivo and in silico analyses. Selected target genes potentially involved in disease responses were assessed by RT-qPCR after different times of inoculation with P. pachyrhizi using different genetic backgrounds related to resistance genes (Rpp2 and Rpp5). R2R3-MYB transcription factors related to lignin synthesis and genes responsive to chitin were significantly induced in the resistant genotypes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

CD4 responses in the setting or suboptimal virological responses to antiretroviral therapy: features, outcomes, and associated factors.

PubMed

Collazos, Julio; Asensi, Víctor; Cartón, José Antonio

2009-07-01

The factors associated with discordant viroimmunological responses following antiretroviral therapy are unclear. We studied 1380 patients who initiated a protease inhibitor (PI)-based antiretroviral regimen and who fulfilled the criteria for inclusion. Of them, 255 (18.5%) had CD4 increases > or =100 cells/microl after 1 year of therapy despite detectable viral load (immunological responders); they were compared with 669 patients (48.5%) who had CD4 increases <100 cells/microl regardless of their final viral load (immunological nonresponders). Immunological responders had higher rates of sexual acquisition of HIV (p = 0.03), lower rates of clinical progression (p = 0.02), higher probabilities of being naive to antiretroviral therapy (p = 0.006) or to PI if antiretroviral experienced (p = 0.03), higher rates of receiving only nucleoside reverse transcriptase inhibitors in addition to the PI (p = 0.04), and lower baseline CD4 counts (p = 0.007) and higher viral loads (p = 0.009), as compared with nonresponders. Multivariate analysis revealed that sexual transmission of HIV (homosexual p = 0.004, heterosexual p = 0.03), no prior PI experience (p = 0.005), absence of clinical progression (p = 0.02), and lower baseline CD4 counts (p = 0.03) were independently associated with immunological response. However, these factors differed according to the patients' prior antiretroviral status, as higher baseline viral load was also associated with immunological response in antiretroviral-experienced patients (p = 0.02), whereas baseline CD4 count (p = 0.007) was the only predictive parameter in antiretroviral-naive patients. We conclude that immunological responses despite suboptimal viral suppression are common. Prior PI experience, HIV transmission category, baseline CD4 counts, and clinical progression were independently predictive of this condition, although the associated factors were different depending on the patient's prior antiretroviral history.

[Facilitating the diagnosis of depression and burnout by identifying demographic and work-related risk and protective factors among nurses].

PubMed

Ádám, Szilvia; Nistor, Anikó; Nistor, Katalin; Cserháti, Zoltán; Mészáros, Veronika

2015-08-09

Depression and burnout are frequent comorbidities among nurses. Despite similar symptoms, their management differ. Therefore, their timely diagnosis is essential. To identify demographic and work-related risk and protective factors of burnout and depression, and facilitate their diagnosis. A cross-sectional study among 1,713 nurses was carried out. Depression and burnout were assessed by the shortened Beck Depression Questionnaire and Maclach Burnout Inventory, respectively. Risk and protective factors were explored using t-tests and analysis of variance. The prevalence of depression and moderate-to-high burnout was 35.1% and 34-74%, respectively. Having a partner/child and longer employment in the outpatient setting protected from burnout. Lack of a partner and male sex emerged as risk factors of depression and depersonalisation, respectively. High prevalence of depression and burnout among nurses poses a significant public health issue. Familiarity with the disease-specific risk and protective factors identified in this research may facilitate timely diagnosis and effective disease management.

Adulthood stress responses in rats are variably altered as a factor of adolescent stress exposure.

PubMed

Moore, Nicole L T; Altman, Daniel E; Gauchan, Sangeeta; Genovese, Raymond F

2016-05-01

Stress exposure during development may influence adulthood stress response severity. The present study investigates persisting effects of two adolescent stressors upon adulthood response to predator exposure (PE). Rats were exposed to underwater trauma (UWT) or PE during adolescence, then to PE after reaching adulthood. Rats were then exposed to predator odor (PO) to test responses to predator cues alone. Behavioral and neuroendocrine assessments were conducted to determine acute effects of each stress experience. Adolescent stress altered behavioral response to adulthood PE. Acoustic startle response was blunted. Bidirectional changes in plus maze exploration were revealed as a factor of adolescent stress type. Neuroendocrine response magnitude did not predict severity of adolescent or adult stress response, suggesting that different adolescent stress events may differentially alter developmental outcomes regardless of acute behavioral or neuroendocrine response. We report that exposure to two different stressors in adolescence may differentially affect stress response outcomes in adulthood. Acute response to an adolescent stressor may not be consistent across all stressors or all dependent measures, and may not predict alterations in developmental outcomes pertaining to adulthood stress exposure. Further studies are needed to characterize factors underlying long-term effects of a developmental stressor.

The Yeast Forkhead Transcription Factors Fkh1 and Fkh2 Regulate Lifespan and Stress Response Together with the Anaphase-Promoting Complex

PubMed Central

Postnikoff, Spike D. L.; Malo, Mackenzie E.; Wong, Berchman; Harkness, Troy A. A.

2012-01-01

Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan. A key function in this process involves the regulation of the cell cycle and stress responses including free radical scavenging. We employed yeast chronological and replicative lifespan assays, as well as oxidative stress assays, to explore the potential evolutionary conservation of function between the FOXOs and the yeast forkhead box transcription factors FKH1 and FKH2. We report that the deletion of both FKH genes impedes normal lifespan and stress resistance, particularly in stationary phase cells, which are non-responsive to caloric restriction. Conversely, increased expression of the FKHs leads to extended lifespan and improved stress response. Here we show the Anaphase-Promoting Complex (APC) genetically interacts with the Fkh pathway, likely working in a linear pathway under normal conditions, as fkh1Δ fkh2Δ post-mitotic survival is epistatic to that observed in apc5CA mutants. However, under stress conditions, post-mitotic survival is dramatically impaired in apc5CA fkh1Δ fkh2Δ, while increased expression of either FKH rescues APC mutant growth defects. This study establishes the FKHs role as evolutionarily conserved regulators of lifespan in yeast and identifies the APC as a novel component of this mechanism under certain conditions, likely through combined regulation of stress response, genomic stability, and cell cycle regulation. PMID:22438832

An extracytoplasmic function sigma factor-dependent periplasmic glutathione peroxidase is involved in oxidative stress response of Shewanella oneidensis

DOE PAGES

Dai, Jingcheng; Wei, Hehong; Tian, Chunyuan; ...

2015-01-01

Background: Bacteria use alternative sigma factors (σs) to regulate condition-specific gene expression for survival and Shewanella harbors multiple ECF (extracytoplasmic function) σ genes and cognate anti-sigma factor genes. Here we comparatively analyzed two of the rpoE-like operons in the strain MR-1: rpoE-rseA-rseB-rseC and rpoE2-chrR. Results: RpoE was important for bacterial growth at low and high temperatures, in the minimal medium, and high salinity. The degP/htrA orthologue, required for growth of Escherichia coli and Pseudomonas aeruginosa at high temperature, is absent in Shewanella, while the degQ gene is RpoE-regulated and is required for bacterial growth at high temperature. RpoE2 was essentialmore » for the optimal growth in oxidative stress conditions because the rpoE2 mutant was sensitive to hydrogen peroxide and paraquat. The operon encoding a ferrochelatase paralogue (HemH2) and a periplasmic glutathione peroxidase (PgpD) was identified as RpoE2-dependent. PgpD exhibited higher activities and played a more important role in the oxidative stress responses than the cytoplasmic glutathione peroxidase CgpD under tested conditions. The rpoE2-chrR operon and the identified regulon genes, including pgpD and hemH2, are coincidently absent in several psychrophilic and/or deep-sea Shewanella strains. Conclusion: In S. oneidensis MR-1, the RpoE-dependent degQ gene is required for optimal growth under high temperature. The rpoE2 and RpoE2-dependent pgpD gene encoding a periplasmic glutathione peroxidase are involved in oxidative stress responses. But rpoE2 is not required for bacterial growth at low temperature and it even affected bacterial growth under salt stress, indicating that there is a tradeoff between the salt resistance and RpoE2-mediated oxidative stress responses.« less

An extracytoplasmic function sigma factor-dependent periplasmic glutathione peroxidase is involved in oxidative stress response of Shewanella oneidensis

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

Dai, Jingcheng; Wei, Hehong; Tian, Chunyuan

Background: Bacteria use alternative sigma factors (σs) to regulate condition-specific gene expression for survival and Shewanella harbors multiple ECF (extracytoplasmic function) σ genes and cognate anti-sigma factor genes. Here we comparatively analyzed two of the rpoE-like operons in the strain MR-1: rpoE-rseA-rseB-rseC and rpoE2-chrR. Results: RpoE was important for bacterial growth at low and high temperatures, in the minimal medium, and high salinity. The degP/htrA orthologue, required for growth of Escherichia coli and Pseudomonas aeruginosa at high temperature, is absent in Shewanella, while the degQ gene is RpoE-regulated and is required for bacterial growth at high temperature. RpoE2 was essentialmore » for the optimal growth in oxidative stress conditions because the rpoE2 mutant was sensitive to hydrogen peroxide and paraquat. The operon encoding a ferrochelatase paralogue (HemH2) and a periplasmic glutathione peroxidase (PgpD) was identified as RpoE2-dependent. PgpD exhibited higher activities and played a more important role in the oxidative stress responses than the cytoplasmic glutathione peroxidase CgpD under tested conditions. The rpoE2-chrR operon and the identified regulon genes, including pgpD and hemH2, are coincidently absent in several psychrophilic and/or deep-sea Shewanella strains. Conclusion: In S. oneidensis MR-1, the RpoE-dependent degQ gene is required for optimal growth under high temperature. The rpoE2 and RpoE2-dependent pgpD gene encoding a periplasmic glutathione peroxidase are involved in oxidative stress responses. But rpoE2 is not required for bacterial growth at low temperature and it even affected bacterial growth under salt stress, indicating that there is a tradeoff between the salt resistance and RpoE2-mediated oxidative stress responses.« less

Prevalence of HIV in pregnant women identified with a risk factor at a tertiary care hospital.

PubMed

Mahmud, Ghazala; Abbas, Shazra

2009-01-01

HIV is an epidemic quite unlike any other, combining the problems of a lifelong medical disease with immense social, psychological, economic and public health consequences. Since we are living in a global village where human interactions has become fast and frequent, diseases like HIV are no more alien to us. HIV/AIDS in Pakistan is slowly gaining recognition as a public health issue of great importance. Objectives of this study were to determine the prevalence of HIV in pregnant women identified with a high risk factor/behaviour at a tertiary care hospital. It is a Descriptive study. All pregnant women attending antenatal booking clinic were assessed via a pre-designed 'Risk assessment questionnaire'. Women identified with a risk factor were offered HIV Rapid screening test (Capillus HIV1/2). Positive (reactive) results on screening test were confirmed with ELISA. During the study period (March 2007-May 2008), out of 5263 antenatal bookings 785 (14%) women were identified with a risk factor. HIV screening test was done in 779 (99%), and 6 women refused testing. Three women (0.3%) were found positive (reactive) on screening. Two out of 3 women were confirmed positive (0.2%) on ELISA. Husbands of both women were tested and one found positive (migrant from Dubai). Second women had history of blood transfusion. Her husband was HIV negative. During the study period, in addition to 2 pregnant women diagnosed as HIV positive through ANC risk screening, 6 confirmed HIV positive women, found pregnant were referred from 'HIV Treatment Centre', Pakistan Institute of Medical Sciences (PIMS) to Prevention of Parent to Child Transmission (PPTCT) centre for obstetric care. Spouses of 5 out of 6 had history of working abroad and extramarital sexual relationships. All positive (8) women were referred to PPTCT centre for further management. A simple 'Risk Assessment Questionnaire' can help us in identifying women who need HIV screening. Sexual transmission still remains the

Data mining model using simple and readily available factors could identify patients at high risk for hepatocellular carcinoma in chronic hepatitis C.

PubMed

Kurosaki, Masayuki; Hiramatsu, Naoki; Sakamoto, Minoru; Suzuki, Yoshiyuki; Iwasaki, Manabu; Tamori, Akihiro; Matsuura, Kentaro; Kakinuma, Sei; Sugauchi, Fuminaka; Sakamoto, Naoya; Nakagawa, Mina; Izumi, Namiki

2012-03-01

Assessment of the risk of hepatocellular carcinoma (HCC) development is essential for formulating personalized surveillance or antiviral treatment plan for chronic hepatitis C. We aimed to build a simple model for the identification of patients at high risk of developing HCC. Chronic hepatitis C patients followed for at least 5 years (n=1003) were analyzed by data mining to build a predictive model for HCC development. The model was externally validated using a cohort of 1072 patients (472 with sustained virological response (SVR) and 600 with nonSVR to PEG-interferon plus ribavirin therapy). On the basis of factors such as age, platelet, albumin, and aspartate aminotransferase, the HCC risk prediction model identified subgroups with high-, intermediate-, and low-risk of HCC with a 5-year HCC development rate of 20.9%, 6.3-7.3%, and 0-1.5%, respectively. The reproducibility of the model was confirmed through external validation (r(2)=0.981). The 10-year HCC development rate was also significantly higher in the high-and intermediate-risk group than in the low-risk group (24.5% vs. 4.8%; p<0.0001). In the high-and intermediate-risk group, the incidence of HCC development was significantly reduced in patients with SVR compared to those with nonSVR (5-year rate, 9.5% vs. 4.5%; p=0.040). The HCC risk prediction model uses simple and readily available factors and identifies patients at a high risk of HCC development. The model allows physicians to identify patients requiring HCC surveillance and those who benefit from IFN therapy to prevent HCC. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Handgrip Strength Cutoff Points to Identify Mobility Limitation in Community-dwelling Older People and Associated Factors.

PubMed

Vasconcelos, K S de Souza; Dias, J M Domingues; Bastone, A de Carvalho; Vieira, R Alvarenga; Andrade, A C de Souza; Perracini, M Rodrigues; Guerra, R Oliveira; Dias, R Corrêa

2016-03-01

Sarcopenia is defined as a progressive and generalized loss of skeletal muscle mass and strength. The specific threshold of muscle weakness that leads to mobility limitations has not been identified. To determine the best cutoff point of handgrip strength for identifying mobility limitation and to investigate the factors associated with muscle weakness and mobility limitation in community-dwelling older people. Transversal study. Cities of Belo Horizonte, Barueri and Santa Cruz in Brazil. 1374 community-dwelling older people from the Frailty study in Brazilian older people (FIBRA Study). Outcomes included muscle weakness determined according to gender-specific handgrip strength cutoff points generated by Receiver Operating Characteristic curves, mobility limitation defined as a gait speed ≤ 0.8 m/s; and a combination of both muscle weakness and mobility limitation. Associated factors included socio-demographic variables, lifestyle, anthropometrics, health conditions, use of health services and disability. The cutoff points of handgrip strength with the best balancing between sensitivity and specificity for mobility limitation were 25.8 kgf for men (sensitivity 69%, specificity 73%) and 17.4 kgf (sensitivity 60%, specificity 66%) for women. Age and disability in instrumental activities of daily living were associated with all outcomes. Women had greater odds of mobility limitation than men. Physical inactivity, body fat, diabetes, depression, sleeping disturbances, number of medications and occurrence of falls remained as significant associated factors in the final model. Handgrip strength can be a useful tool to identify mobility limitation in clinical practice. Interventions to prevent or minimize impacts of sarcopenia should stimulate physical activity and improvement of body composition in addition to the management of chronic diseases and disabilities.

A Path Analysis to Identify the Psychosocial Factors Influencing Physical Activity and Bone Health in Middle-School Girls

PubMed Central

Sharma, Shreela V.; Hoelscher, Deanna M.; Kelder, Steven H.; Diamond, Pamela M.; Day, R. Sue; Hergenroeder, Albert C.

2011-01-01

Background The purpose of this study was to identify pathways used by psychosocial factors to influence physical activity and bone health in middle-school girls. Methods Baseline data from the Incorporating More Physical Activity and Calcium in Teens (IMPACT) study collected in 2001 to 2003 were used. IMPACT was a 1 1/2 years nutrition and physical activity intervention study designed to improve bone density in 717 middle-school girls in Texas. Structural Equations Modeling was used to examine the interrelationships and identify the direct and indirect pathways used by various psychosocial and environmental factors to influence physical activity and bone health. Results Results show that physical activity self-efficacy and social support (friend, family engagement, and encouragement in physical activity) had a significant direct and indirect influence on physical activity with participation in sports teams as the mediator. Participation in sports teams had a direct effect on both physical activity (β= 0.20, P < .05) and bone health and (β=0.13, P < .05). Conclusion The current study identified several direct and indirect pathways that psychosocial factors use to influence physical activity and bone health among adolescent girls. These findings are critical for the development of effective interventions for promoting bone health in this population. PMID:19953837

Identifying Frailty Levels and Associated Factors in a Population Living in the Context of Poverty and Social Vulnerability.

PubMed

Zazzetta, M S; Gomes, G A O; Orlandi, F S; Gratão, A C M; Vasilceac, F A; Gramani-Say, K; Ponti, M A; Castro, P C; Pavarini, S C I; Menezes, A L C; Nascimento, C M C; Cominetti, M R

2017-01-01

This study aimed to investigate a vulnerable population living in the context of poverty in a Brazilian municipality, in order to identify the factors that are associated with frailty syndrome in elderly people. From the total population living in the area, a random sample of 363 community-dwelling people, 60 years and older, age and gender-stratified, was selected to participate in the research. After losses, a sample of 304 older adults was classified as non-frail, pre-frail and frail. According to the Fried frailty criteria, the prevalence was 12.2% for non-frail individuals, 60.5% pre-frail and 27.3% frail. The main factors associated with frailty in the studied sample were low level of physical activity (OR: 5.2, 95%CI: 2.5-11.0), the occurrence of two or more falls within 12 months (OR: 3.1, 95%CI: 1.4-7.1), mobility deficits (OR: 3.0, 95%CI: 1.5-5.8), and depressive symptoms (OR: 1.9, 95%CI: 1.1-3.7). This study identified the most important factors that must be evaluated to identify frailty syndrome in a socially vulnerable population in the context of poverty. The data should help to encourage effective strategies concerning public health policies for this population.

A path analysis to identify the psychosocial factors influencing physical activity and bone health in middle-school girls.

PubMed

Sharma, Shreela V; Hoelscher, Deanna M; Kelder, Steven H; Diamond, Pamela M; Day, R Sue; Hergenroeder, Albert C

2009-09-01

The purpose of this study was to identify pathways used by psychosocial factors to influence physical activity and bone health in middle-school girls. Baseline data from the Incorporating More Physical Activity and Calcium in Teens (IMPACT) study collected in 2001 to 2003 were used. IMPACT was a 1 1/2 years nutrition and physical activity intervention study designed to improve bone density in 717 middle-school girls in Texas. Structural Equations Modeling was used to examine the interrelationships and identify the direct and indirect pathways used by various psychosocial and environmental factors to influence physical activity and bone health. Results show that physical activity self-efficacy and social support (friend, family engagement, and encouragement in physical activity) had a significant direct and indirect influence on physical activity with participation in sports teams as the mediator. Participation in sports teams had a direct effect on both physical activity (beta = 0.20, P < .05) and bone health and (beta = 0.13, P < .05). The current study identified several direct and indirect pathways that psychosocial factors use to influence physical activity and bone health among adolescent girls. These findings are critical for the development of effective interventions for promoting bone health in this population.

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

PubMed

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

2018-03-29

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

FOREVER YOUNG FLOWER Negatively Regulates Ethylene Response DNA-Binding Factors by Activating an Ethylene-Responsive Factor to Control Arabidopsis Floral Organ Senescence and Abscission.

PubMed

Chen, Wei-Han; Li, Pei-Fang; Chen, Ming-Kun; Lee, Yung-I; Yang, Chang-Hsien

2015-08-01

In this study of Arabidopsis (Arabidopsis thaliana), we investigated the relationship between FOREVER YOUNG FLOWER (FYF) and Ethylene Response DNA-binding Factors (EDFs) and functionally analyzed a key FYF target, an Ethylene-Responsive Factor (ERF), that controls flower senescence/abscission. Ectopic expression of EDF1/2/3/4 caused promotion of flower senescence/abscission and the activation of the senescence-associated genes. The presence of a repressor domain in EDFs and the enhancement of the promotion of senescence/abscission in EDF1/2/3/4+SRDX (converting EDFs to strong repressors by fusion with the ERF-associated amphiphilic repression motif repression domain SRDX) transgenic plants suggested that EDFs act as repressors. The significant reduction of β-glucuronidase (GUS) expression by 35S:FYF in EDF1/2/3/4:GUS plants indicates that EDF1/2/3/4 functions downstream of FYF in regulating flower senescence/abscission. In this study, we also characterized an ERF gene, FOREVER YOUNG FLOWER UP-REGULATING FACTOR1 (FUF1), which is up-regulated by FYF during flower development. Ectopic expression of FUF1 caused similar delayed flower senescence/abscission as seen in 35S:FYF plants. This phenotype was correlated with deficient abscission zone formation, ethylene insensitivity, and down-regulation of EDF1/2/3/4 and abscission-associated genes in 35S:FUF1 flowers. In contrast, significant promotion of flower senescence/abscission and up-regulation of EDF1/2/3/4 were observed in 35S:FUF1+SRDX transgenic dominant-negative plants, in which FUF1 is converted to a potent repressor by fusion to an SRDX-suppressing motif. Thus, FUF1 acts as an activator in suppressing EDF1/2/3/4 function and senescence/abscission of the flowers. Our results reveal that FYF regulates flower senescence/abscission by negatively regulating EDF1/2/3/4, which is the downstream gene in the ethylene response, by activating FUF1 in Arabidopsis. © 2015 American Society of Plant Biologists. All Rights

An integrated genomic approach identifies persistent tumor suppressive effects of transforming growth factor-β in human breast cancer

PubMed Central

2014-01-01

Introduction Transforming growth factor-βs (TGF-βs) play a dual role in breast cancer, with context-dependent tumor-suppressive or pro-oncogenic effects. TGF-β antagonists are showing promise in early-phase clinical oncology trials to neutralize the pro-oncogenic effects. However, there is currently no way to determine whether the tumor-suppressive effects of TGF-β are still active in human breast tumors at the time of surgery and treatment, a situation that could lead to adverse therapeutic responses. Methods Using a breast cancer progression model that exemplifies the dual role of TGF-β, promoter-wide chromatin immunoprecipitation and transcriptomic approaches were applied to identify a core set of TGF-β-regulated genes that specifically reflect only the tumor-suppressor arm of the pathway. The clinical significance of this signature and the underlying biology were investigated using bioinformatic analyses in clinical breast cancer datasets, and knockdown validation approaches in tumor xenografts. Results TGF-β-driven tumor suppression was highly dependent on Smad3, and Smad3 target genes that were specifically enriched for involvement in tumor suppression were identified. Patterns of Smad3 binding reflected the preexisting active chromatin landscape, and target genes were frequently regulated in opposite directions in vitro and in vivo, highlighting the strong contextuality of TGF-β action. An in vivo-weighted TGF-β/Smad3 tumor-suppressor signature was associated with good outcome in estrogen receptor-positive breast cancer cohorts. TGF-β/Smad3 effects on cell proliferation, differentiation and ephrin signaling contributed to the observed tumor suppression. Conclusions Tumor-suppressive effects of TGF-β persist in some breast cancer patients at the time of surgery and affect clinical outcome. Carefully tailored in vitro/in vivo genomic approaches can identify such patients for exclusion from treatment with TGF-β antagonists. PMID:24890385

Response of algal metrics to nutrients and physical factors and identification of nutrient thresholds in agricultural streams

USGS Publications Warehouse

Black, R.W.; Moran, P.W.; Frankforter, J.D.

2011-01-01

Many streams within the United States are impaired due to nutrient enrichment, particularly in agricultural settings. The present study examines the response of benthic algal communities in agricultural and minimally disturbed sites from across the western United States to a suite of environmental factors, including nutrients, collected at multiple scales. The first objective was to identify the relative importance of nutrients, habitat and watershed features, and macroinvertebrate trophic structure to explain algal metrics derived from deposition and erosion habitats. The second objective was to determine if thresholds in total nitrogen (TN) and total phosphorus (TP) related to algal metrics could be identified and how these thresholds varied across metrics and habitats. Nutrient concentrations within the agricultural areas were elevated and greater than published threshold values. All algal metrics examined responded to nutrients as hypothesized. Although nutrients typically were the most important variables in explaining the variation in each of the algal metrics, environmental factors operating at multiple scales also were important. Calculated thresholds for TN or TP based on the algal metrics generated from samples collected from erosion and deposition habitats were not significantly different. Little variability in threshold values for each metric for TN and TP was observed. The consistency of the threshold values measured across multiple metrics and habitats suggest that the thresholds identified in this study are ecologically relevant. Additional work to characterize the relationship between algal metrics, physical and chemical features, and nuisance algal growth would be of benefit to the development of nutrient thresholds and criteria. ?? 2010 The Author(s).

Response of algal metrics to nutrients and physical factors and identification of nutrient thresholds in agricultural streams.

PubMed

Black, Robert W; Moran, Patrick W; Frankforter, Jill D

2011-04-01

Many streams within the United States are impaired due to nutrient enrichment, particularly in agricultural settings. The present study examines the response of benthic algal communities in agricultural and minimally disturbed sites from across the western United States to a suite of environmental factors, including nutrients, collected at multiple scales. The first objective was to identify the relative importance of nutrients, habitat and watershed features, and macroinvertebrate trophic structure to explain algal metrics derived from deposition and erosion habitats. The second objective was to determine if thresholds in total nitrogen (TN) and total phosphorus (TP) related to algal metrics could be identified and how these thresholds varied across metrics and habitats. Nutrient concentrations within the agricultural areas were elevated and greater than published threshold values. All algal metrics examined responded to nutrients as hypothesized. Although nutrients typically were the most important variables in explaining the variation in each of the algal metrics, environmental factors operating at multiple scales also were important. Calculated thresholds for TN or TP based on the algal metrics generated from samples collected from erosion and deposition habitats were not significantly different. Little variability in threshold values for each metric for TN and TP was observed. The consistency of the threshold values measured across multiple metrics and habitats suggest that the thresholds identified in this study are ecologically relevant. Additional work to characterize the relationship between algal metrics, physical and chemical features, and nuisance algal growth would be of benefit to the development of nutrient thresholds and criteria.

Suppressor of gamma response 1 (SOG1) encodes a putative transcription factor governing multiple responses to DNA damage

PubMed Central

Yoshiyama, Kaoru; Conklin, Phillip A.; Huefner, Neil D.; Britt, Anne B.

2009-01-01

The Arabidopsis sog1-1 (suppressor of gamma response) mutant was originally isolated as a second-site suppressor of the radiosensitive phenotype of seeds defective in the repair endonuclease XPF. Here, we report that SOG1 encodes a putative transcription factor. This gene is a member of the NAC domain [petunia NAM (no apical meristem) and Arabidopsis ATAF1, 2 and CUC2] family (a family of proteins unique to land plants). Hundreds of genes are normally up-regulated in Arabidopsis within an hour of treatment with ionizing radiation; the induction of these genes requires the damage response protein kinase ATM, but not the related kinase ATR. Here, we find that SOG1 is also required for this transcriptional up-regulation. In contrast, the SOG1-dependent checkpoint response observed in xpf mutant seeds requires ATR, but does not require ATM. Thus, phenotype of the sog1-1 mutant mimics aspects of the phenotypes of both atr and atm mutants in Arabidopsis, suggesting that SOG1 participates in pathways governed by both of these sensor kinases. We propose that, in plants, signals related to genomic stress are processed through a single, central transcription factor, SOG1. PMID:19549833

Identifying Risk Factors for Drug Use in an Iranian Treatment Sample: A Prediction Approach Using Decision Trees.

PubMed

Amirabadizadeh, Alireza; Nezami, Hossein; Vaughn, Michael G; Nakhaee, Samaneh; Mehrpour, Omid

2018-05-12

Substance abuse exacts considerable social and health care burdens throughout the world. The aim of this study was to create a prediction model to better identify risk factors for drug use. A prospective cross-sectional study was conducted in South Khorasan Province, Iran. Of the total of 678 eligible subjects, 70% (n: 474) were randomly selected to provide a training set for constructing decision tree and multiple logistic regression (MLR) models. The remaining 30% (n: 204) were employed in a holdout sample to test the performance of the decision tree and MLR models. Predictive performance of different models was analyzed by the receiver operating characteristic (ROC) curve using the testing set. Independent variables were selected from demographic characteristics and history of drug use. For the decision tree model, the sensitivity and specificity for identifying people at risk for drug abuse were 66% and 75%, respectively, while the MLR model was somewhat less effective at 60% and 73%. Key independent variables in the analyses included first substance experience, age at first drug use, age, place of residence, history of cigarette use, and occupational and marital status. While study findings are exploratory and lack generalizability they do suggest that the decision tree model holds promise as an effective classification approach for identifying risk factors for drug use. Convergent with prior research in Western contexts is that age of drug use initiation was a critical factor predicting a substance use disorder.

Transcriptome-wide identification of Camellia sinensis WRKY transcription factors in response to temperature stress.

PubMed

Wu, Zhi-Jun; Li, Xing-Hui; Liu, Zhi-Wei; Li, Hui; Wang, Yong-Xin; Zhuang, Jing

2016-02-01

Tea plant [Camellia sinensis (L.) O. Kuntze] is a leaf-type healthy non-alcoholic beverage crop, which has been widely introduced worldwide. Tea is rich in various secondary metabolites, which are important for human health. However, varied climate and complex geography have posed challenges for tea plant survival. The WRKY gene family in plants is a large transcription factor family that is involved in biological processes related to stress defenses, development, and metabolite synthesis. Therefore, identification and analysis of WRKY family transcription factors in tea plant have a profound significance. In the present study, 50 putative C. sinensis WRKY proteins (CsWRKYs) with complete WRKY domain were identified and divided into three Groups (Group I-III) on the basis of phylogenetic analysis results. The distribution of WRKY family transcription factors among plantae, fungi, and protozoa showed that the number of WRKY genes increased in higher plant, whereas the number of these genes did not correspond to the evolutionary relationships of different species. Structural feature and annotation analysis results showed that CsWRKY proteins contained WRKYGQK/WRKYGKK domains and C2H2/C2HC-type zinc-finger structure: D-X18-R-X1-Y-X2-C-X4-7-C-X23-H motif; CsWRKY proteins may be associated with the biological processes of abiotic and biotic stresses, tissue development, and hormone and secondary metabolite biosynthesis. Temperature stresses suggested that the candidate CsWRKY genes were involved in responses to extreme temperatures. The current study established an extensive overview of the WRKY family transcription factors in tea plant. This study also provided a global survey of CsWRKY transcription factors and a foundation of future functional identification and molecular breeding.

Using Medicare Data to Identify Individuals Who Are Electricity Dependent to Improve Disaster Preparedness and Response

PubMed Central

DeSalvo, Karen; Finne, Kristen; Worrall, Chris; Bogdanov, Alina; Dinkler, Ayame; Babcock, Sarah; Kelman, Jeffrey

2014-01-01

During a disaster or prolonged power outage, individuals who use electricity-dependent medical equipment are often unable to operate it and seek care in acute care settings or local shelters. Public health officials often report that they do not have proactive and systematic ways to rapidly identify and assist these individuals. In June 2013, we piloted a first-in-the-nation emergency preparedness drill in which we used Medicare claims data to identify individuals with electricity-dependent durable medical equipment during a disaster and securely disclosed it to a local health department. We found that Medicare claims data were 93% accurate in identifying individuals using a home oxygen concentrator or ventilator. The drill findings suggest that claims data can be useful in improving preparedness and response for electricity-dependent populations. PMID:24832404

Using Medicare data to identify individuals who are electricity dependent to improve disaster preparedness and response.

PubMed

DeSalvo, Karen; Lurie, Nicole; Finne, Kristen; Worrall, Chris; Bogdanov, Alina; Dinkler, Ayame; Babcock, Sarah; Kelman, Jeffrey

2014-07-01

During a disaster or prolonged power outage, individuals who use electricity-dependent medical equipment are often unable to operate it and seek care in acute care settings or local shelters. Public health officials often report that they do not have proactive and systematic ways to rapidly identify and assist these individuals. In June 2013, we piloted a first-in-the-nation emergency preparedness drill in which we used Medicare claims data to identify individuals with electricity-dependent durable medical equipment during a disaster and securely disclosed it to a local health department. We found that Medicare claims data were 93% accurate in identifying individuals using a home oxygen concentrator or ventilator. The drill findings suggest that claims data can be useful in improving preparedness and response for electricity-dependent populations.

IDENTIFYING ELEVEN FACTORS OF SERVICE MARKETING MIX (4PS) EFFECTIVE ON TENDENCY OF PATIENTS TOWARD PRIVATE HOSPITAL

PubMed Central

Hosseini, Seyed Mojtaba; Etesaminia, Samira; Jafari, Mehrnoosh

2016-01-01

Introduction: One of the important factors of correct management is to identify the reasons for patient tendency toward private hospitals. This study measures these factors based on service marketing mixes. Patients and methods: This study used a cross sectional descriptive methodology. The study was conducted during 6 months in 2015. The studied population included patients of private hospitals in Tehran. Random sampling was used (n = 200). Data was collected by an author-made questionnaire for service marketing factors. Reliability and validity of the questionnaire were confirmed. Data analysis was done using factor analysis test in SPSS 20. Results: The results showed that constant attendance of physicians and nurses has the highest effect (0.707%) on patient tendency toward private hospitals. PMID:27999486

Pilot Critical Incident Reports as a Means to Identify Human Factors of Remotely Piloted Aircraft

NASA Technical Reports Server (NTRS)

Hobbs, Alan; Cardoza, Colleen; Null, Cynthia

2016-01-01

It has been estimated that aviation accidents are typically preceded by numerous minor incidents arising from the same causal factors that ultimately produced the accident. Accident databases provide in-depth information on a relatively small number of occurrences, however incident databases have the potential to provide insights into the human factors of Remotely Piloted Aircraft System (RPAS) operations based on a larger volume of less-detailed reports. Currently, there is a lack of incident data dealing with the human factors of unmanned aircraft systems. An exploratory study is being conducted to examine the feasibility of collecting voluntary critical incident reports from RPAS pilots. Twenty-three experienced RPAS pilots volunteered to participate in focus groups in which they described critical incidents from their own experience. Participants were asked to recall (1) incidents that revealed a system flaw, or (2) highlighted a case where the human operator contributed to system resilience or mission success. Participants were asked to only report incidents that could be included in a public document. During each focus group session, a note taker produced a de-identified written record of the incident narratives. At the end of the session, participants reviewed each written incident report, and made edits and corrections as necessary. The incidents were later analyzed to identify contributing factors, with a focus on design issues that either hindered or assisted the pilot during the events. A total of 90 incidents were reported. Human factor issues included the impact of reduced sensory cues, traffic separation in the absence of an out-the-window view, control latencies, vigilance during monotonous and ultra-long endurance flights, control station design considerations, transfer of control between control stations, the management of lost link procedures, and decision-making during emergencies. Pilots participated willingly and enthusiastically in the study

FACTORS AFFECTING SENSITIVITY OF CHEMICAL AND ECOLOGICAL RESPONSES OF MARINE EMBAYMEMTS TO NITROGEN LOADING

EPA Science Inventory

This paper summarizes an ongoing examination of the primary factors that affect sensitivity of marine embayment responses to nitrogen loading. Included is a discussion of two methods for using these factors: classification of embayments into discrete sensitivity classes and norma...

Application of positive matrix factorization to identify potential sources of PAHs in soil of Dalian, China.

PubMed

Wang, Degao; Tian, Fulin; Yang, Meng; Liu, Chenlin; Li, Yi-Fan

2009-05-01

Soil derived sources of polycyclic aromatic hydrocarbons (PAHs) in the region of Dalian, China were investigated using positive matrix factorization (PMF). Three factors were separated based on PMF for the statistical investigation of the datasets both in summer and winter. These factors were dominated by the pattern of single sources or groups of similar sources, showing seasonal and regional variations. The main sources of PAHs in Dalian soil in summer were the emissions from coal combustion average (46%), diesel engine (30%), and gasoline engine (24%). In winter, the main sources were the emissions from coal-fired boiler (72%), traffic average (20%), and gasoline engine (8%). These factors with strong seasonality indicated that coal combustion in winter and traffic exhaust in summer dominated the sources of PAHs in soil. These results suggested that PMF model was a proper approach to identify the sources of PAHs in soil.

Host Response Signature to Staphylococcus aureus Alpha-Hemolysin Implicates Pulmonary Th17 Response

PubMed Central

Zhou, Tong; Moreno-Vinasco, Liliana; Hollett, Brian; Garcia, Joe G. N.

2012-01-01

Staphylococcus aureus pneumonia causes significant morbidity and mortality. Alpha-hemolysin (Hla), a pore-forming cytotoxin of S. aureus, has been identified through animal models of pneumonia as a critical virulence factor that induces lung injury. In spite of considerable molecular knowledge of how this cytotoxin injures the host, the precise host response to Hla in the context of infection remains poorly understood. We employed whole-genome expression profiling of infected lungs to define the host response to wild-type S. aureus compared with the response to an Hla-deficient isogenic mutant in experimental pneumonia. These data provide a complete expression profile at 4 and at 24 h postinfection, revealing a unique response to the toxin-expressing strain. Gene ontogeny analysis revealed significant differences in the extracellular matrix and cardiomyopathy pathways, both of which govern cellular interactions in the tissue microenvironment. Evaluation of individual transcript responses to Hla-secreting staphylococci was notable for upregulation of host cytokine and chemokine genes, including the p19 subunit of interleukin-23. Consistent with this observation, the cellular immune response to infection was characterized by a prominent Th17 response to the wild-type pathogen. These findings define specific host mRNA responses to Hla-producing S. aureus, coupling the pulmonary Th17 response to the secretion of this cytotoxin. Expression profiling to define the host response to a single virulence factor proved to be a valuable tool in identifying pathways for further investigation in S. aureus pneumonia. This approach may be broadly applicable to the study of bacterial toxins, defining host pathways that can be targeted to mitigate toxin-induced disease. PMID:22733574

pH modulates the binding of early growth response protein 1 transcription factor to DNA.

PubMed

Mikles, David C; Bhat, Vikas; Schuchardt, Brett J; Deegan, Brian J; Seldeen, Kenneth L; McDonald, Caleb B; Farooq, Amjad

2013-08-01

The transcription factor early growth response protein (EGR)1 orchestrates a plethora of signaling cascades involved in cellular homeostasis, and its downregulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with an increase in pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as His382 by virtue of the fact that its replacement by nonionizable residues abolishes the pH dependence of the binding of EGR1 to DNA. Notably, His382 inserts into the major groove of DNA, and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, His382 is mainly conserved across other members of the EGR family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating the protein-DNA interactions that are central to this family of transcription factors. Collectively, our findings reveal an unexpected but a key step in the molecular recognition of the EGR family of transcription factors, and suggest that they may act as sensors of pH within the intracellular environment. © 2013 FEBS.

An analysis of thermal response factors and how to reduce their computational time requirement

NASA Technical Reports Server (NTRS)

Wiese, M. R.

1982-01-01

Te RESFAC2 version of the Thermal Response Factor Program (RESFAC) is the result of numerous modifications and additions to the original RESFAC. These modifications and additions have significantly reduced the program's computational time requirement. As a result of this work, the program is more efficient and its code is both readable and understandable. This report describes what a thermal response factor is; analyzes the original matrix algebra calculations and root finding techniques; presents a new root finding technique and streamlined matrix algebra; supplies ten validation cases and their results.

Physical Therapists' Ability to Identify Psychological Factors and Their Self-Reported Competence to Manage Chronic Low Back Pain.

PubMed

Brunner, Emanuel; Dankaerts, Wim; Meichtry, André; O'Sullivan, Kieran; Probst, Michel

2018-06-01

In the management of chronic low back pain (LBP), identifying and managing more patients who are at high risk and who have psychological barriers to recovery is important yet difficult. The objective of this study was to test physical therapists' ability to allocate patients into risk stratification groups, test correlations between therapists' assessments of psychological factors and patient questionnaires, and explore relationships between psychological factors and therapists' self-reported competence to manage patients with chronic LBP. This was a pragmatic, observational study. Patients completed the STarT Back Tool (SBT, for risk stratification), the Four-Dimensional Symptom Questionnaire (distress, depression, anxiety), and the Tampa Scale of Kinesiophobia (kinesiophobia) prior to the intake session. After this session, physical therapists estimated patient prognostic risk using the 3 SBT categories and rated patient psychological factors using a 0-to-10 scale. Finally, therapists reported their self-reported competence to manage the patient. Intraclass and Spearman rank correlations tested correlations between therapists' intuitive assessments and patient questionnaires. A linear-mixed model explored relationships between psychological factors and therapists' self-reported competence. Forty-nine patients were managed by 20 therapists. Therapists accurately estimated SBT risk allocation in only 41% of patients. Correlations between therapist perceptions and patient questionnaires were moderate for distress (r = 0.602) and fair for depression (r = 0.304) and anxiety (r = 0.327). There was no correlation for kinesiophobia (r = -0.007). Patient distress was identified as a negative predictor of therapists' self-reported competence. This was a cross-sectional study, conducted in only 1 center. Physical therapists were not very accurate at allocating patients into risk stratification groups or identifying psychological factors. Therapists' self

Nerve Growth Factor Inhibits Sympathetic Neurons' Response to an Injury Cytokine

NASA Astrophysics Data System (ADS)

Shadiack, Annette M.; Vaccariello, Stacey A.; Sun, Yi; Zigmond, Richard E.

1998-06-01

Axonal damage to adult peripheral neurons causes changes in neuronal gene expression. For example, axotomized sympathetic, sensory, and motor neurons begin to express galanin mRNA and protein, and recent evidence suggests that galanin plays a role in peripheral nerve regeneration. Previous studies in sympathetic and sensory neurons have established that galanin expression is triggered by two consequences of nerve transection: the induction of leukemia inhibitory factor (LIF) and the reduction in the availability of the target-derived factor, nerve growth factor. It is shown in the present study that no stimulation of galanin expression occurs following direct application of LIF to intact neurons in the superior cervical sympathetic ganglion. Injection of animals with an antiserum to nerve growth factor concomitant with the application of LIF, on the other hand, does stimulate galanin expression. The data suggest that the response of neurons to an injury factor, LIF, is affected by whether the neurons still receive trophic signals from their targets.

Production of migration inhibitory factor in response to bacterial and fungal antigens in patients with untreated Graves' disease

PubMed Central

Wall, Jack R.; Ryan, E. Ann

1980-01-01

Tests for the production of migration inhibitory factor by peripheral blood leukocytes in response to ubiquitous bacterial and fungal antigens were carried out in patients with untreated Graves' disease and in healthy control subjects. Dose-response studies, tests for the production of this factor after 72 hours' stimulation with phytohemagglutinin as a test for reserve, and tests before and after 24 hours' preculture to deplete suppressor cells were also performed in some patients. The antigens used were Candida, Trichophyton-Oidiomyces-Epidermophyton, mumps live attenuated virus and purified protein derivative of tuberculin. The production of migration inhibitory factor was measured by the agarose microdroplet method. The production of migration inhibitory factor in response to all the antigens except mumps virus was slightly greater in the patients than in the control subjects, although the differences were not significant. The dose-response characteristics and the production of migration inhibitory factor after stimulation with phytohemagglutinin were similar in the two groups. The production of migration inhibitory factor in response to suboptimal concentrations of Candida, Trichophyton-Oidiomyces-Epidermophyton and mumps virus was not enhanced in either group after 24 hours' preculture apart from a slight increase in response to mumps virus in the patients. These results fail to support the suggestion that patients with Graves' disease have a deficiency of suppressor cells. PMID:6446374

A Genome-wide Regulatory Network Identifies Key Transcription Factors for Memory CD8+ T Cell Development

PubMed Central

Hu, Guangan; Chen, Jianzhu

2014-01-01

Memory CD8+ T cell development is defined by the expression of a specific set of memory signature genes (MSGs). Despite recent progress, many components of the transcriptional control of memory CD8+ T cell development are still unknown. To identify transcription factors (TFs) and their interactions in memory CD8+ T cell development, we construct a genome-wide regulatory network and apply it to identify key TFs that regulate MSGs. Most of the known TFs in memory CD8+ T cell development are rediscovered and about a dozen new TFs are also identified. Sox4, Bhlhe40, Bach2 and Runx2 are experimentally verified and Bach2 is further shown to promote both development and recall proliferation of memory CD8+ T cells through Prdm1 and Id3. Gene perturbation study identifies the mode of interactions among the TFs with Sox4 as a hub. The identified TFs and insights into their interactions should facilitate further dissection of molecular mechanisms underlying memory CD8+ T cell development. PMID:24335726