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.

Inhibition of platelet activation by lachrymatory factor synthase (LFS)-silenced (tearless) onion juice.

PubMed

Thomson, Susan J; Rippon, Paula; Butts, Chrissie; Olsen, Sarah; Shaw, Martin; Joyce, Nigel I; Eady, Colin C

2013-11-06

Onion and garlic are renowned for their roles as functional foods. The health benefits of garlic are attributed to di-2-propenyl thiosulfinate (allicin), a sulfur compound found in disrupted garlic but not found in disrupted onion. Recently, onions have been grown with repressed lachrymatory factor synthase (LFS) activity, which causes these onions to produce increased amounts of di-1-propenyl thiosulfinate, an isomer of allicin. This investigation into the key health attributes of LFS-silenced (tearless) onions demonstrates that they have some attributes more similar to garlic and that this is likely due to the production of novel thiosulfinate or metabolites. The key finding was that collagen-induced in vitro platelet aggregation was significantly reduced by tearless onion extract over normal onion extract. Thiosulfinate or derived compounds were shown not to be responsible for the observed changes in the inflammatory response of AGS (stomach adenocarcinoma) cells to tumor necrosis factor alpha (TNFα) when pretreated with model onion juices. A preliminary rat feeding trial indicated that the tearless onions may also play a key role in reducing weight gain.

Key factors influencing the intention of telecare adoption: an institutional perspective.

PubMed

Liu, Chung-Feng

2011-05-01

The objective of this study was to explore key factors of influence on the adoption of telecare by care institutions. This investigation was based on an extensive Technology-Organization-Environment framework comprising the four constructs of technology, organization, environment, and the project planning as well as corresponding variables. This study utilized a self-administered questionnaire for data collection, focusing on the managers of all 339 nursing homes in Taiwan for the census survey. A total of 70 valid questionnaires yielded a response rate of 20.65%. After analyzing the responses through the Partial Least Squares approach, government support, technological knowledge, supplier support, team skills, and compatibility were found to be the five key factors that positively impact intention to adopt telecare from an institutional perspective. The results of this study indicated that care institutions, for the most part, are willing to develop telecare and are already incorporating preliminary applications of telecare, such as distance learning and resident positioning. Solutions to potential issues related to implementing telecare in practice are also proposed in this study.

Water deficit-induced changes in transcription factor expression in maize seedlings

USDA-ARS?s Scientific Manuscript database

Plants tolerate water deficits by regulating gene networks controlling cellular and physiological traits to modify growth and development. Transcription factor (TFs) directed regulation of transcription within these gene networks is key to eliciting appropriate responses. In this study, reverse tran...

Molecular characterization and mRNA expression of two key enzymes of hypoxia-sensing pathways in eastern oysters Crassostrea virginica (Gmelin): Hypoxia-inducible factor α (HIF-α) and HIF-prolyl hydroxylase (PHD)

PubMed Central

Piontkivska, Helen; Chung, J. Sook; Ivanina, Anna V.; Sokolov, Eugene P.; Techa, Sirinart; Sokolova, Inna M.

2010-01-01

Oxygen homeostasis is crucial for development, survival and normal function of all metazoans. A family of transcription factors called hypoxia-inducible factors (HIF) is critical in mediating the adaptive responses to reduced oxygen availability. The HIF transcription factor consists of a constitutively expressed β subunit and an oxygen-dependent α subunit; the abundance of the latter determines the activity of HIF and is regulated by a family of O2- and Fe2+-dependent enzymes prolyl hydroxylases (PHDs). Currently very little is known about the function of this important pathway and the molecular structure of its key players in hypoxia-tolerant intertidal mollusks including oysters, which are among the animal champions of anoxic and hypoxic tolerance and thus can serve as excellent models to study the role of HIF cascade in adaptations to oxygen deficiency. We have isolated transcripts of two key components of the oxygen sensing pathway - the oxygen-regulated HIF-α subunit and PHD - from an intertidal mollusk, the eastern oyster Crassostrea virginica, and determined the transcriptional responses of these two genes to anoxia, hypoxia and cadmium (Cd) stress. HIF-α and PHD homologs from eastern oysters C. virginica show significant sequence similarity and share key functional domains with the earlier described isoforms from vertebrates and invertebrates. Phylogenetic analysis shows that genetic diversification of HIF and PHD isoforms occurred within the vertebrate lineage indicating functional diversification and specialization of the oxygen-sensing pathways in this group, which parallels situation observed for many other important genes. HIF-α and PHD homologs are broadly expressed at the mRNA level in different oyster tissues and show transcriptional responses to prolonged hypoxia in the gills consistent with their putative role in oxygen sensing and the adaptive response to hypoxia. Similarity in amino acid sequence, domain structure and transcriptional responses between HIF-α and PHD homologs from oysters and other invertebrate and vertebrate species implies the highly conserved functions of these genes throughout the evolutionary history of animals, in accordance with their critical role in oxygen sensing and homeostasis. PMID:21106446

Crosstalk between the Unfolded Protein Response and NF-κB-Mediated Inflammation in the Progression of Chronic Kidney Disease

PubMed Central

Cruz, Gaile L.; Dickhout, Jeffrey G.

2015-01-01

The chronic inflammatory response is emerging as an important therapeutic target in progressive chronic kidney disease. A key transcription factor in the induction of chronic inflammation is NF-κB. Recent studies have demonstrated that sustained activation of the unfolded protein response (UPR) can initiate this NF-κB signaling phenomenon and thereby induce chronic kidney disease progression. A key factor influencing chronic kidney disease progression is proteinuria and this condition has now been demonstrated to induce sustained UPR activation. This review details the crosstalk between the UPR and NF-κB pathways as pertinent to chronic kidney disease. We present potential tools to study this phenomenon as well as potential therapeutics that are emerging to regulate the UPR. These therapeutics may prevent inflammation specifically induced in the kidney due to proteinuria-induced sustained UPR activation. PMID:25977931

Attribution of Observed Streamflow Changes in Key British Columbia Drainage Basins

NASA Astrophysics Data System (ADS)

Najafi, Mohammad Reza; Zwiers, Francis W.; Gillett, Nathan P.

2017-11-01

We study the observed decline in summer streamflow in four key river basins in British Columbia (BC), Canada, using a formal detection and attribution (D&A) analysis procedure. Reconstructed and simulated streamflow is generated using the semidistributed variable infiltration capacity hydrologic model, which is driven by 1/16° gridded observations and downscaled climate model data from the Coupled Model Intercomparison Project phase 5 (CMIP5), respectively. The internal variability of the regional hydrologic components using 5100 years of streamflow was simulated using CMIP5 preindustrial control runs. Results show that the observed changes in summer streamflow are inconsistent with simulations representing the responses to natural forcing factors alone, while the response to anthropogenic and natural forcing factors combined is detected in these changes. A two-signal D&A analysis indicates that the effects of anthropogenic (ANT) forcing factors are discernable from natural forcing in BC, albeit with large uncertainties.

From Loose Groups to Effective Teams: The Nine Key Factors of the Team Landscape.

ERIC Educational Resources Information Center

Sheard, A. G.; Kakabadse, A. P.

2002-01-01

A loose group of individuals working on a task differs from an effective team on nine factors: clearly defined goals, priorities, roles and responsibilities, self-awareness, leadership, group dynamics, communications, content, and infrastructure. Ways to eliminate barriers and speed formation of effective teams could be based on those factors.…

Drug discrimination under two concurrent fixed-interval fixed-interval schedules.

PubMed

McMillan, D E; Li, M

2000-07-01

Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a two-key concurrent fixed-interval (FI) 100-s FI 200-s schedule of food presentation, and later tinder a concurrent FI 40-s FI 80-s schedule, in which the FI component with the shorter time requirement reinforced responding on one key after drug administration (pentobarbital-biased key) and on the other key after saline administration (saline-biased key). After responding stabilized under the concurrent FI 100-s FI 200-s schedule, pigeons earned an average of 66% (after pentobarbital) to 68% (after saline) of their reinforcers for responding under the FI 100-s component of the concurrent schedule. These birds made an average of 70% of their responses on both the pentobarbital-biased key after the training dose of pentobarbital and the saline-biased key after saline. After responding stabilized under the concurrent FI 40-s FI 80-s schedule, pigeons earned an average of 67% of their reinforcers for responding under the FI 40 component after both saline and the training dose of pentobarbital. These birds made an average of 75% of their responses on the pentobarbital-biased key after the training dose of pentobarbital, but only 55% of their responses on the saline-biased key after saline. In test sessions preceded by doses of pentobarbital, chlordiazepoxide, ethanol, phencyclidine, or methamphetamine, the dose-response curves were similar under these two concurrent schedules. Pentobarbital, chlordiazepoxide, and ethanol produced dose-dependent increases in responding on the pentobarbital-biased key as the doses increased. For some birds, at the highest doses of these drugs, the dose-response curve turned over. Increasing doses of phencyclidine produced increased responding on the pentobarbital-biased key in some, but not all, birds. After methamphetamine, responding was largely confined to the saline-biased key. These data show that pigeons can perform drug discriminations under concurrent schedules in which the reinforcement frequency under the schedule components differs only by a factor of two, and that when other drugs are substituted for the training drugs they produce dose-response curves similar to the curves produced by these drugs under other concurrent interval schedules.

Regulation of cotton (Gossypium hirsutum) drought responses by mitogen-activated protein (MAP) kinase cascade-mediated phosphorylation of GhWRKY59.

PubMed

Li, Fangjun; Li, Maoying; Wang, Ping; Cox, Kevin L; Duan, Liusheng; Dever, Jane K; Shan, Libo; Li, Zhaohu; He, Ping

2017-09-01

Drought is a key limiting factor for cotton (Gossypium spp.) production, as more than half of the global cotton supply is grown in regions with high water shortage. However, the underlying mechanism of the response of cotton to drought stress remains elusive. By combining genome-wide transcriptome profiling and a loss-of-function screen using virus-induced gene silencing, we identified Gossypium hirsutum GhWRKY59 as an important transcription factor that regulates the drought stress response in cotton. Biochemical and genetic analyses revealed a drought stress-activated mitogen-activated protein (MAP) kinase cascade consisting of GhMAP3K15-Mitogen-activated Protein Kinase Kinase 4 (GhMKK4)-Mitogen-activated Protein Kinase 6 (GhMPK6) that directly phosphorylates GhWRKY59 at residue serine 221. Interestingly, GhWRKY59 is required for dehydration-induced expression of GhMAPK3K15, constituting a positive feedback loop of GhWRKY59-regulated MAP kinase activation in response to drought stress. Moreover, GhWRKY59 directly binds to the W-boxes of DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN 2 (GhDREB2), which encodes a dehydration-inducible transcription factor regulating the plant hormone abscisic acid (ABA)-independent drought response. Our study identified a complete MAP kinase cascade that phosphorylates and activates a key WRKY transcription factor, and elucidated a regulatory module, consisting of GhMAP3K15-GhMKK4-GhMPK6-GhWRKY59-GhDREB2, that is involved in controlling the cotton drought response. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children.

PubMed

De Leonibus, C; Chatelain, P; Knight, C; Clayton, P; Stevens, A

2016-11-01

The response to growth hormone in humans is dependent on phenotypic, genetic and environmental factors. The present study in children with growth hormone deficiency (GHD) collected worldwide characterised gene-environment interactions on growth response to recombinant human growth hormone (r-hGH). Growth responses in children are linked to latitude, and we found that a correlate of latitude, summer daylight exposure (SDE), was a key environmental factor related to growth response to r-hGH. In turn growth response was determined by an interaction between both SDE and genes known to affect growth response to r-hGH. In addition, analysis of associated networks of gene expression implicated a role for circadian clock pathways and specifically the developmental transcription factor NANOG. This work provides the first observation of gene-environment interactions in children treated with r-hGH.

Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children

PubMed Central

De Leonibus, C; Chatelain, P; Knight, C; Clayton, P; Stevens, A

2016-01-01

The response to growth hormone in humans is dependent on phenotypic, genetic and environmental factors. The present study in children with growth hormone deficiency (GHD) collected worldwide characterised gene–environment interactions on growth response to recombinant human growth hormone (r-hGH). Growth responses in children are linked to latitude, and we found that a correlate of latitude, summer daylight exposure (SDE), was a key environmental factor related to growth response to r-hGH. In turn growth response was determined by an interaction between both SDE and genes known to affect growth response to r-hGH. In addition, analysis of associated networks of gene expression implicated a role for circadian clock pathways and specifically the developmental transcription factor NANOG. This work provides the first observation of gene–environment interactions in children treated with r-hGH. PMID:26503811

Local Text Cohesion, Reading Ability and Individual Science Aspirations: Key Factors Influencing Comprehension in Science Classes

ERIC Educational Resources Information Center

Hall, Sophie S.; Kowalski, Rebecca; Paterson, Kevin B.; Basran, Jaskaran; Filik, Ruth; Maltby, John

2015-01-01

In response to the concern of the need to improve the scientific skills of school children, this study investigated the influence of text design (in terms of text cohesion) and individual differences, with the aim of identifying pathways to improving science education in early secondary school (Key Stage 3). One hundred and four secondary school…

Exploring Students' Emotional Responses and Participation in an Online Peer Assessment Activity: A Case Study

ERIC Educational Resources Information Center

Cheng, Kun-Hung; Hou, Huei-Tse; Wu, Sheng-Yi

2014-01-01

In the social interactions among individuals of learning communities, including those individuals engaged in peer assessment activities, emotion may be a key factor in learning. However, research regarding the emotional response of learners in online peer assessment activities is relatively scarce. Detecting learners' emotion when they make…

Students' Response to Academic Setback: "Growth Mindset" as a Buffer against Demotivation

ERIC Educational Resources Information Center

Aditomo, Anindito

2015-01-01

It is important to understand why some students are able to bounce back following setbacks, while others become de-motivated and suffer negative consequences. This study tests a model which places students' beliefs about ability (Dweck & Leggett, 1988) as a key factor which may influence students' motivational response to setbacks and…

Institutionalization versus Self-Regulation: A Contextual Analysis of Responsibility among Adolescent Sportsmen

ERIC Educational Resources Information Center

Long, Thierry; Pantaleon, Nathalie; Bruant, Gerard

2008-01-01

The present study, which sought to analyse adolescent sportsmen's representations of responsibility, was mainly guided by the philosophical literature on this topic. A body of literature suggests that the contextual factors of sport practice, particularly regarding the rules that regulate play, may have a key role in the building of such…

Modeling crown structural responses to competing vegetation control, thinning, fertilization, and Swiss needle cast in coastal Douglas-fir of the Pacific Northwest, USA.

Treesearch

A.R. Weiskittel; D.A. Maguire; R.A. Monserud

2007-01-01

Crown structure is a key variable influencing stand productivity, but its reported response to various stand factors has differed. This can be partially attributed to lack of a unified study on crown response to intensive management or stand health. In this analysis of several Douglas-fir (Pseudotsuga menziesii var. menziesii [...

Personal Factors that Influence Deaf College Students' Academic Success

ERIC Educational Resources Information Center

Albertini, John A.; Kelly, Ronald R.; Matchett, Mary Karol

2012-01-01

Research tells us that academic preparation is key to deaf students' success at college. Yet, that is not the whole story. Many academically prepared students drop out during their first year. This study identified entering deaf college students' personal factors as assessed by their individual responses to both the "Noel-Levitz College…

Analysis of the Choice for Public and Private Education.

ERIC Educational Resources Information Center

Gemello, John M.; Osman, Jack W.

Key factors influencing the decision to attend private school are identified in this paper. It looks at the factors accounting for varying rates of private school attendance and estimates the responsiveness of such attendance to government support. It studies the variation in private school attendance rates at three levels: across states, across…

Federal Public Health Workforce Development: An Evidence-Based Approach for Defining Competencies.

PubMed

Mumford, Karen; Young, Andrea C; Nawaz, Saira

2016-01-01

This study reports the use of exploratory factor analysis to describe essential skills and knowledge for an important segment of the domestic public health workforce-Centers for Disease Control and Prevention (CDC) project officers-using an evidence-based approach to competency development and validation. A multicomponent survey was conducted. Exploratory factor analysis was used to examine the underlying domains and relationships between competency domains and key behaviors. The Cronbach α coefficient determined the reliability of the overall scale and identified factors. All domestic (US state, tribe, local, and territorial) grantees who received funding from the CDC during fiscal year 2011 to implement nonresearch prevention or intervention programs were invited to participate in a Web-based questionnaire. A total of 34 key behaviors representing knowledge, skills, and abilities, grouped in 7 domains-communication, grant administration and management, public health applied science and knowledge, program planning and development, program management, program monitoring and improvement, and organizational consultation-were examined. There were 795 responses (58% response rate). A total of 6 factors were identified with loadings of 0.40 or more for all 34 behavioral items. The Cronbach α coefficient was 0.95 overall and ranged between 0.73 and 0.91 for the factors. This study provides empirical evidence for the construct validity of 6 competencies and 34 key behaviors important for CDC project officers and serves as an important first step to evidence-driven workforce development efforts in public health.

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.

Rice phytochrome-interacting factor-like protein OsPIL1 functions as a key regulator of internode elongation and induces a morphological response to drought stress

PubMed Central

Todaka, Daisuke; Nakashima, Kazuo; Maruyama, Kyonoshin; Kidokoro, Satoshi; Osakabe, Yuriko; Ito, Yusuke; Matsukura, Satoko; Fujita, Yasunari; Yoshiwara, Kyouko; Ohme-Takagi, Masaru; Kojima, Mikiko; Sakakibara, Hitoshi; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

2012-01-01

The mechanisms for plant growth restriction during stress conditions remains unclear. Here, we demonstrate that a phytochrome-interacting factor-like protein, OsPIL1/OsPIL13, acts as a key regulator of reduced internode elongation in rice under drought conditions. The level of OsPIL1 mRNA in rice seedlings grown under nonstressed conditions with light/dark cycles oscillated in a circadian manner with peaks in the middle of the light period. Under drought stress conditions, OsPIL1 expression was inhibited during the light period. We found that OsPIL1 was highly expressed in the node portions of the stem using promoter-glucuronidase analysis. Overexpression of OsPIL1 in transgenic rice plants promoted internode elongation. In contrast, transgenic rice plants with a chimeric repressor resulted in short internode sections. Alteration of internode cell size was observed in OsPIL1 transgenic plants, indicating that differences in cell size cause the change in internode length. Oligoarray analysis revealed OsPIL1 downstream genes, which were enriched for cell wall-related genes responsible for cell elongation. These data suggest that OsPIL1 functions as a key regulatory factor of reduced plant height via cell wall-related genes in response to drought stress. This regulatory system may be important for morphological stress adaptation in rice under drought conditions. PMID:22984180

Arabidopsis BPM proteins function as substrate adaptors to a cullin3-based E3 ligase to affect fatty acid metabolism in plants.

PubMed

Chen, Liyuan; Lee, Joo Hyun; Weber, Henriette; Tohge, Takayuki; Witt, Sandra; Roje, Sanja; Fernie, Alisdair R; Hellmann, Hanjo

2013-06-01

Regulation of transcriptional processes is a critical mechanism that enables efficient coordination of the synthesis of required proteins in response to environmental and cellular changes. Transcription factors require accurate activity regulation because they play a critical role as key mediators assuring specific expression of target genes. In this work, we show that cullin3-based E3 ligases have the potential to interact with a broad range of ethylene response factor (ERF)/APETALA2 (AP2) transcription factors, mediated by Math-BTB/POZ (for Meprin and TRAF [tumor necrosis factor receptor associated factor] homolog)-Broad complex, Tramtrack, Bric-a-brac/Pox virus and Zinc finger) proteins. The assembly with an E3 ligase causes degradation of their substrates via the 26S proteasome, as demonstrated for the wrinkled1 ERF/AP2 protein. Furthermore, loss of Math-BTB/POZ proteins widely affects plant development and causes altered fatty acid contents in mutant seeds. Overall, this work demonstrates a link between fatty acid metabolism and E3 ligase activities in plants and establishes CUL3-based E3 ligases as key regulators in transcriptional processes that involve ERF/AP2 family members.

Factors influencing societal response of nanotechnology: an expert stakeholder analysis

NASA Astrophysics Data System (ADS)

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.

Interactions of soil conditioner with other limiting factors to achieve high crop yields. [Lycopersicon esculentum

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

Wallace, A.; Abouzamzam, A.M.

Tomato (Lycopersicon esculentum Mill. cv. Tropic) was used as a test plant in evaluating the interactions for simultaneously correcting deficiencies of N and P and improving physical properties of soil with a soil conditioner. The three limiting factors were improved singly and in all possible combinations. There was response to each input. The least response to the soil conditioner was with N and P, and the most response was when N and P were also used. The combined effect appeared to be synergistic. The results emphasize that the best crop management system involves overcoming as many limiting factors as possible.more » This is the key to high-yield agriculture.« less

Genome-Wide Identification of Binding Sites Defines Distinct Functions for Caenorhabditis elegans PHA-4/FOXA in Development and Environmental Response

PubMed Central

Zhong, Mei; Niu, Wei; Lu, Zhi John; Sarov, Mihail; Murray, John I.; Janette, Judith; Raha, Debasish; Sheaffer, Karyn L.; Lam, Hugo Y. K.; Preston, Elicia; Slightham, Cindie; Hillier, LaDeana W.; Brock, Trisha; Agarwal, Ashish; Auerbach, Raymond; Hyman, Anthony A.; Gerstein, Mark; Mango, Susan E.; Kim, Stuart K.; Waterston, Robert H.; Reinke, Valerie; Snyder, Michael

2010-01-01

Transcription factors are key components of regulatory networks that control development, as well as the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans that permits global identification of the binding sites for transcription factors using chromatin immunoprecipitation and deep sequencing. We describe and validate this strategy, and apply it to the transcription factor PHA-4, which plays critical roles in organ development and other cellular processes. We identified thousands of binding sites for PHA-4 during formation of the embryonic pharynx, and also found a role for this factor during the starvation response. Many binding sites were found to shift dramatically between embryos and starved larvae, from developmentally regulated genes to genes involved in metabolism. These results indicate distinct roles for this regulator in two different biological processes and demonstrate the versatility of transcription factors in mediating diverse biological roles. PMID:20174564

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.

Key role of integrin α(IIb)β (3) signaling to Syk kinase in tissue factor-induced thrombin generation.

PubMed

van der Meijden, Paola E J; Feijge, Marion A H; Swieringa, Frauke; Gilio, Karen; Nergiz-Unal, Reyhan; Hamulyák, Karly; Heemskerk, Johan W M

2012-10-01

The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.

Performance indicators: healthcare professionals' views.

PubMed

Gu, Xiuzhu; Itoh, Kenji

2016-08-08

Purpose - The purpose of this paper is to capture factors behind professional views of indicator usefulness as a common structure for assessing healthcare performance and their important characteristics to design limited key performance indicators (PIs) for holistic hospital management. Design/methodology/approach - Two surveys were conducted using self-administered questionnaires, in which hospital manager/staff respondents were asked to rate the 52 PIs' usefulness. In total, 228 manager and 894 staff responses were collected. Findings - Eight factors were elicited from manager and staff responses as performance measures with 72 percent cumulative variance accounted for. Hospital managers and staff showed similar performance measure perceptions: high-utility acknowledgment on safety, operational efficiency and patient/employee satisfaction but relatively low-employee development concerns. Manager indicator usefulness perceptions were rather homogeneous and significantly higher than staff for almost all performance measures. Practical implications - Homogeneous manager views mean that a single key PI set for hospital management may be established regardless of hospital attributes. The following aspects may be measures that should be managed in a healthcare organization based on their key PIs: patient/employee safety, operational efficiency, financial effectiveness and patient/employee satisfaction. Originality/value - This is a pilot study on hospital management PIs in Japan. The eight-dimensional factor structure and findings about healthcare provider perceptions may be useful for healthcare management.

Avian relationships with wildfire at two dry forest locations with different historical fire regimes

Treesearch

Quresh Latif; Jamie Sanderlin; Vicki Saab; William Block; Jonathan Dudley

2016-01-01

Wildfire is a key factor influencing bird community composition in western North American forests. We need to understand species and community responses to wildfire and how responses vary regionally to effectively manage dry conifer forests for maintaining biodiversity. We compared avian relationships with wildfire burn severity between two dry forest...

The Engagement Continuum Model Using Corporate Social Responsibility as an Intervention for Sustained Employee Engagement: Research Leading Practice

ERIC Educational Resources Information Center

Valentin, Marie Anttonitte; Valentin, Celestino C.; Nafukho, Fredrick Muyia

2015-01-01

Purpose: The purpose of this paper is to explore implications of motivational potential that are highly correlated to the self-determination theory (SDT) (intrinsic motivating factors), in relation to corporate social responsibility (CSR). This paper specifies key antecedents of engagement within the theoretical framework of the self-determination…

Preschool Teachers' Professional Training, Observational Feedback, Child-Centered Beliefs and Motivation: Direct and Indirect Associations with Social and Emotional Responsiveness

ERIC Educational Resources Information Center

Lang, Sarah N.; Mouzourou, Chryso; Jeon, Lieny; Buettner, Cynthia K.; Hur, Eunhye

2017-01-01

Background: Young children's social and emotional competence is a key predictor of their current and future academic and social success. Although preschool teachers are critical socializing agent of children's social and emotional development, we know little about factors associated with preschool teachers' social and emotional responsiveness.…

Understanding Classroom Feedback Practices: A Study of New Zealand Student Experiences, Perceptions, and Emotional Responses

ERIC Educational Resources Information Center

Harris, Lois R.; Brown, Gavin T.; Harnett, Jennifer A.

2014-01-01

While feedback is a key factor for improving student learning, little is known about how students understand and experience feedback within the classroom. This study analysed 193 New Zealand primary and secondary students' survey responses alongside drawings of their understandings and experiences of feedback to examine how they experience,…

Innovation, Nostalgia, and the Politics of Educational Change. Responses

ERIC Educational Resources Information Center

Labaree, David F.

2006-01-01

In this reaction, the author concentrates on evaluating the study's broader interpretive claims. He states that the articles reviewed have the following three purposes: (1) to explore the ways in which a variety of factors shape school change over time; (2) to show how the five factors combine at key points in the story to create what Ivor…

The "Responsive Classroom" Approach and Fifth Grade Students' Math and Science Anxiety and Self-Efficacy

ERIC Educational Resources Information Center

Griggs, Marissa Swaim; Rimm-Kaufman, Sara E.; Merritt, Eileen G.; Patton, Christine L.

2013-01-01

Self-efficacy forecasts student persistence and achievement in challenging subjects. Thus, it is important to understand factors that contribute to students' self-efficacy, a key factor in their success in math and science. The current cross-sectional study examined the contribution of students' gender and math and science anxiety as well as…

ROS is Required for Alternatively Activated Macrophage Differentiation | Center for Cancer Research

Cancer.gov

Macrophages are key regulators in host inflammatory responses. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) are responsible for inducing macrophage differentiation from monocytes. GM-CSF or M-CSF-differentiated macrophages can be further differentiated, or polarized, to more specialized cells. Classically activated, or M1, macrophages have immune-stimulatory properties and cytotoxic function against tumor cells. Alternatively activated, or M2, macrophages have low cytotoxic function but high tissue-remodeling activity. There are also M2-like cells called tumor-associated macrophages (TAMs) that are responsible for many tumor-promoting activities. Blocking the function of TAMs inhibits tumorigenesis.

Characterization of the Host Response to Pichinde Virus Infection in the Syrian Golden Hamster by Species-Specific Kinome Analysis*

PubMed Central

Falcinelli, Shane; Gowen, Brian B.; Trost, Brett; Napper, Scott; Kusalik, Anthony; Johnson, Reed F.; Safronetz, David; Prescott, Joseph; Wahl-Jensen, Victoria; Jahrling, Peter B.; Kindrachuk, Jason

2015-01-01

The Syrian golden hamster has been increasingly used to study viral hemorrhagic fever (VHF) pathogenesis and countermeasure efficacy. As VHFs are a global health concern, well-characterized animal models are essential for both the development of therapeutics and vaccines as well as for increasing our understanding of the molecular events that underlie viral pathogenesis. However, the paucity of reagents or platforms that are available for studying hamsters at a molecular level limits the ability to extract biological information from this important animal model. As such, there is a need to develop platforms/technologies for characterizing host responses of hamsters at a molecular level. To this end, we developed hamster-specific kinome peptide arrays to characterize the molecular host response of the Syrian golden hamster. After validating the functionality of the arrays using immune agonists of defined signaling mechanisms (lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α), we characterized the host response in a hamster model of VHF based on Pichinde virus (PICV1) infection by performing temporal kinome analysis of lung tissue. Our analysis revealed key roles for vascular endothelial growth factor (VEGF), interleukin (IL) responses, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, and Toll-like receptor (TLR) signaling in the response to PICV infection. These findings were validated through phosphorylation-specific Western blot analysis. Overall, we have demonstrated that hamster-specific kinome arrays are a robust tool for characterizing the species-specific molecular host response in a VHF model. Further, our results provide key insights into the hamster host response to PICV infection and will inform future studies with high-consequence VHF pathogens. PMID:25573744

Fever as a risk factor for increased response to vitamin K antagonists: a review of the evidence and potential mechanisms.

PubMed

Self, Timothy H; Oliphant, Carrie S; Reaves, Anne B; Richardson, Amy M; Sands, Christopher W

2015-01-01

Numerous factors affect the response to vitamin K antagonists (VKA) including age, dietary vitamin K, other drugs, pharmacogenetics, and disease states. In antithrombotic guidelines, fever is mentioned as a factor that may increase response to VKA. The purpose of this article is to review the available evidence regarding the effect of fever on response to VKA, and to discuss possible mechanisms of this effect. We performed a search of the English literature from 1943 to June 2014, using the key words fever AND warfarin, acenocoumarol, phenprocoumon, coumarin anticoagulants and VKA; fever AND vitamin K dependent clotting factors II, VII, IX, and X. One animal investigation and 6 studies in humans suggest fever increases response to VKA, but one study did not find a significant effect. The magnitude of this effect is variable. Possible mechanisms for the increased effect of VKA associated with fever are increased catabolism of vitamin K dependent clotting factors, decreased vitamin K intake, and inhibition of VKA metabolism. More rigorous studies are needed to confirm that fever increases response to warfarin and other VKA. Copyright © 2014 Elsevier Ltd. All rights reserved.

The molecular bases of the suicidal brain

PubMed Central

Turecki, Gustavo

2017-01-01

Suicide ranks among the leading causes of death around the world, and takes a heavy emotional and public health toll on most societies. Both distal and proximal factors contribute to suicidal behaviour. Distal factors — such as familial and genetic predisposition, as well as early-life adversity — increase the lifetime risk of suicide. They alter responses to stress and other processes through epigenetic modification of genes and associated changes in gene expression, and through the regulation of emotional and behavioural traits. Proximal factors associate with the precipitation of a suicidal event and include alterations in key neurotransmitter systems, inflammatory changes and glial dysfunction in the brain. This Review explores the key molecular changes associated with suicidality, and presents some promising avenues for future research. PMID:25354482

WRKY transcription factors: key components in abscisic acid signalling.

PubMed

Rushton, Deena L; Tripathi, Prateek; Rabara, Roel C; Lin, Jun; Ringler, Patricia; Boken, Ashley K; Langum, Tanner J; Smidt, Lucas; Boomsma, Darius D; Emme, Nicholas J; Chen, Xianfeng; Finer, John J; Shen, Qingxi J; Rushton, Paul J

2012-01-01

WRKY transcription factors (TFs) are key regulators of many plant processes, including the responses to biotic and abiotic stresses, senescence, seed dormancy and seed germination. For over 15 years, limited evidence has been available suggesting that WRKY TFs may play roles in regulating plant responses to the phytohormone abscisic acid (ABA), notably some WRKY TFs are ABA-inducible repressors of seed germination. However, the roles of WRKY TFs in other aspects of ABA signalling, and the mechanisms involved, have remained unclear. Recent significant progress in ABA research has now placed specific WRKY TFs firmly in ABA-responsive signalling pathways, where they act at multiple levels. In Arabidopsis, WRKY TFs appear to act downstream of at least two ABA receptors: the cytoplasmic PYR/PYL/RCAR-protein phosphatase 2C-ABA complex and the chloroplast envelope-located ABAR-ABA complex. In vivo and in vitro promoter-binding studies show that the target genes for WRKY TFs that are involved in ABA signalling include well-known ABA-responsive genes such as ABF2, ABF4, ABI4, ABI5, MYB2, DREB1a, DREB2a and RAB18. Additional well-characterized stress-inducible genes such as RD29A and COR47 are also found in signalling pathways downstream of WRKY TFs. These new insights also reveal that some WRKY TFs are positive regulators of ABA-mediated stomatal closure and hence drought responses. Conversely, many WRKY TFs are negative regulators of seed germination, and controlling seed germination appears a common function of a subset of WRKY TFs in flowering plants. Taken together, these new data demonstrate that WRKY TFs are key nodes in ABA-responsive signalling networks. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

Ribosome Synthesis and MAPK Activity Modulate Ionizing Radiation-Induced Germ Cell Apoptosis in Caenorhabditis elegans

PubMed Central

Eberhard, Ralf; Stergiou, Lilli; Hofmann, E. Randal; Hofmann, Jen; Haenni, Simon; Teo, Youjin; Furger, André; Hengartner, Michael O.

2013-01-01

Synthesis of ribosomal RNA by RNA polymerase I (RNA pol I) is an elemental biological process and is key for cellular homeostasis. In a forward genetic screen in C. elegans designed to identify DNA damage-response factors, we isolated a point mutation of RNA pol I, rpoa-2(op259), that leads to altered rRNA synthesis and a concomitant resistance to ionizing radiation (IR)-induced germ cell apoptosis. This weak apoptotic IR response could be phenocopied when interfering with other factors of ribosome synthesis. Surprisingly, despite their resistance to DNA damage, rpoa-2(op259) mutants present a normal CEP-1/p53 response to IR and increased basal CEP-1 activity under normal growth conditions. In parallel, rpoa-2(op259) leads to reduced Ras/MAPK pathway activity, which is required for germ cell progression and physiological germ cell death. Ras/MAPK gain-of-function conditions could rescue the IR response defect in rpoa-2(op259), pointing to a function for Ras/MAPK in modulating DNA damage-induced apoptosis downstream of CEP-1. Our data demonstrate that a single point mutation in an RNA pol I subunit can interfere with multiple key signalling pathways. Ribosome synthesis and growth-factor signalling are perturbed in many cancer cells; such an interplay between basic cellular processes and signalling might be critical for how tumours evolve or respond to treatment. PMID:24278030

The influence of historical climate changes on Southern Ocean marine predator populations: a comparative analysis.

PubMed

Younger, Jane L; Emmerson, Louise M; Miller, Karen J

2016-02-01

The Southern Ocean ecosystem is undergoing rapid physical and biological changes that are likely to have profound implications for higher-order predators. Here, we compare the long-term, historical responses of Southern Ocean predators to climate change. We examine palaeoecological evidence for changes in the abundance and distribution of seabirds and marine mammals, and place these into context with palaeoclimate records in order to identify key environmental drivers associated with population changes. Our synthesis revealed two key factors underlying Southern Ocean predator population changes; (i) the availability of ice-free ground for breeding and (ii) access to productive foraging grounds. The processes of glaciation and sea ice fluctuation were key; the distributions and abundances of elephant seals, snow petrels, gentoo, chinstrap and Adélie penguins all responded strongly to the emergence of new breeding habitat coincident with deglaciation and reductions in sea ice. Access to productive foraging grounds was another limiting factor, with snow petrels, king and emperor penguins all affected by reduced prey availability in the past. Several species were isolated in glacial refugia and there is evidence that refuge populations were supported by polynyas. While the underlying drivers of population change were similar across most Southern Ocean predators, the individual responses of species to environmental change varied because of species specific factors such as dispersal ability and environmental sensitivity. Such interspecific differences are likely to affect the future climate change responses of Southern Ocean marine predators and should be considered in conservation plans. Comparative palaeoecological studies are a valuable source of long-term data on species' responses to environmental change that can provide important insights into future climate change responses. This synthesis highlights the importance of protecting productive foraging grounds proximate to breeding locations, as well as the potential role of polynyas as future Southern Ocean refugia. © 2015 John Wiley & Sons Ltd.

Early warning systems and rapid response to the deteriorating patient in hospital: A realist evaluation.

PubMed

McGaughey, Jennifer; O'Halloran, Peter; Porter, Sam; Trinder, John; Blackwood, Bronagh

2017-12-01

To test the Rapid Response Systems programme theory against actual practice components of the Rapid Response Systems implemented to identify those contexts and mechanisms which have an impact on the successful achievement of desired outcomes in practice. Rapid Response Systems allow deteriorating patients to be recognized using Early Warning Systems, referred early via escalation protocols and managed at the bedside by competent staff. Realist evaluation. The research design was an embedded multiple case study approach of four wards in two hospitals in Northern Ireland which followed the principles of Realist Evaluation. We used various mixed methods including individual and focus group interviews, observation of nursing practice between June-November 2010 and document analysis of Early Warning Systems audit data between May-October 2010 and hospital acute care training records over 4.5 years from 2003-2008. Data were analysed using NiVivo8 and SPPS. A cross-case analysis highlighted similar patterns of factors which enabled or constrained successful recognition, referral and response to deteriorating patients in practice. Key enabling factors were the use of clinical judgement by experienced nurses and the empowerment of nurses as a result of organizational change associated with implementation of Early Warning System protocols. Key constraining factors were low staffing and inappropriate skill mix levels, rigid implementation of protocols and culturally embedded suboptimal communication processes. Successful implementation of Rapid Response Systems was dependent on adopting organizational and cultural changes that facilitated staff empowerment, flexible implementation of protocols and ongoing experiential learning. © 2017 John Wiley & Sons Ltd.

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.

Mass Atrocity: Prevention and Response

DTIC Science & Technology

2011-04-01

Larry Strobel (PKSOI), Colonel Lorelei Coplen (PKSOI) and Jim Armstead (Washington & Lee ) superbly guided their group discussions with minimal... Strobel (PKSOI) A mass atrocity situation will have several key lo- gistical considerations which are normally factors in other rapid response scenarios...termediaries in USAID, the UN, or the host nation. Moral, Ethical & Legal Issues Working Group Moderator: J. Holmes Armstead (Washington and Lee

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, supplemented by appropriate responses by local responders and the general population within the hazard zones, regional planning is essential to success. The remainder of this Executive Summary provides summary guidance for response planning in three areas: (1) Public Protection Strategy details the importance of early, adequate shelter followed by informed evacuation. (2) Responder Priorities identify how to protect response personnel, perform regional situational assessment, and support public safety. (3) Key Planning Considerations refute common myths and provide important information on planning how to respond in the aftermath of nuclear terrorism.« less

The nonlinear, complex sequential organization of behavior in schizophrenic patients: neurocognitive strategies and clinical correlations.

PubMed

Paulus, M P; Perry, W; Braff, D L

1999-09-01

Thought disorder is a hallmark of schizophrenia and can be inferred from disorganized behavior. Measures of the sequential organization of behavior are important because they reflect the cognitive processes of the selection and sequencing of behavioral elements, which generate observable and analyzable behavioral patterns. In this context, sequences of choices generated by schizophrenic patients in a two-choice guessing task fluctuate significantly, which reflects an "oscillating dysregulation" between highly predictable and highly unpredictable subsequences within a single test session. In this study, we aimed to clarify the significance of dysregulation by seeing whether demographic, clinical, neuropsychological, and psychological measures predict the degree of dysregulation observed on this two-choice task. Thirty schizophrenic patients repeatedly performed a LEFT or RIGHT key press that was followed by a stimulus, which occurred randomly on the left or right side of the computer screen. Thus, the stimulus location had nothing to do with the key press behavior. The range of key press sequence predictabilities as measured by the dynamical entropy was used to quantify the dysregulation of response sequences and reflects the range of fixity and randomness of the responses. A factor analysis was performed and step-wise multiple regression analyses were used to relate the factor scores to demographic, clinical, symptomatic, Wisconsin Card Sorting Test (WCST), and Rorschach variables. The LEFT/RIGHT key press sequences were determined by three factors: 1) the degree of win-stay/lose-shift strategy; 2) the degree of contextual influence on the current choice; and 3) the degree of dysregulation on the choice task. Demographic and clinical variables did not predict any of the three response patterns on the choice task. In contrast, the WCST and Rorschach test predicted performance on various factors of choice task response patterns. Schizophrenic patients employ several rules, i.e., "win-stay/lose-shift" and "decide according to the previous choice," that fluctuate significantly when generating sequences on this task, confirming that a basic behavioral dysregulation occurs in a single schizophrenic subject across a single test session. The organization or the "temporal architecture" of the behavioral sequences is not related to symptoms per se, but is related to deficits in executive functioning, problem solving, and perceptual organizational abilities.

Arabidopsis BPM Proteins Function as Substrate Adaptors to a CULLIN3-Based E3 Ligase to Affect Fatty Acid Metabolism in Plants[W

PubMed Central

Chen, Liyuan; Lee, Joo Hyun; Weber, Henriette; Tohge, Takayuki; Witt, Sandra; Roje, Sanja; Fernie, Alisdair R.; Hellmann, Hanjo

2013-01-01

Regulation of transcriptional processes is a critical mechanism that enables efficient coordination of the synthesis of required proteins in response to environmental and cellular changes. Transcription factors require accurate activity regulation because they play a critical role as key mediators assuring specific expression of target genes. In this work, we show that CULLIN3-based E3 ligases have the potential to interact with a broad range of ETHYLENE RESPONSE FACTOR (ERF)/APETALA2 (AP2) transcription factors, mediated by MATH-BTB/POZ (for Meprin and TRAF [tumor necrosis factor receptor associated factor] homolog)-Broad complex, Tramtrack, Bric-a-brac/Pox virus and Zinc finger) proteins. The assembly with an E3 ligase causes degradation of their substrates via the 26S proteasome, as demonstrated for the WRINKLED1 ERF/AP2 protein. Furthermore, loss of MATH-BTB/POZ proteins widely affects plant development and causes altered fatty acid contents in mutant seeds. Overall, this work demonstrates a link between fatty acid metabolism and E3 ligase activities in plants and establishes CUL3-based E3 ligases as key regulators in transcriptional processes that involve ERF/AP2 family members. PMID:23792371

Factors associated with the persuasiveness of direct-to-consumer advertising on HPV vaccination among young women.

PubMed

Manika, Danae; Ball, Jennifer G; Stout, Patricia A

2014-01-01

This quantitative study explored young women's response to direct-to-consumer pharmaceutical advertising (DTCA) for a human papillomavirus (HPV) vaccine. In particular, the study examined (a) the association of factors stemming from consumer research with actual and intended behavioral responses to DTCA for HPV and (b) key elements drawn from commonly used health-related theories to determine the strongest associations with behavioral intentions regarding the HPV vaccine. Survey findings showed that vaccinated women indicated that DTCA played a role in their decision to get vaccinated against HPV more so than those who were not vaccinated. Trust in DTCA for an HPV vaccine brand was significantly related to intentions to seek more information about the vaccine. Also, perceived barriers had the only significant association with behavioral intentions when taking into account perceived threat and response efficacy. These results provide practical implications for key industry decision makers and health communication professionals on the design of effective theory-based health communication message content for an HPV vaccine brand with consequent social implications.

The Future of Clinical Education: Opportunities and Challenges from Allied Health Deans' Perspective.

PubMed

Romig, Barbara D; Tucker, Ann W; Hewitt, Anne M; O'Sullivan Maillet, Julie

2017-01-01

There is limited information and consensus on the future of clinical education and the key factors impacting allied health (AH) clinical training. AH deans identified both opportunities and challenges impacting clinical education based on a proposed educational model. From July 2013 to March 2014, 61 deans whose institutions were 2013 members of the Association of Schools of Allied Health Professions (ASAHP) participated in a three-round Delphi survey. Agreement on the relative importance of and the ability to impact the key factors was analyzed. Impact was evaluated for three groups: individual, collective, and both individual and collective deans. AH deans' responses were summarized and refined; individual items were accepted or rerated until agreement was achieved or study conclusion. Based on the deans' ratings of importance and impact, 159 key factors within 13 clinical education categories emerged as important for the future of clinical education. Agreement was achieved on 107 opportunities and 52 challenges. The Delphi technique generated new information where little existed specific to AH deans' perspectives on AH clinical education. This research supports the Key Factors Impacting Allied Health Clinical Education conceptual model proposed earlier and provides a foundation for AH deans to evaluate opportunities and challenges impacting AH clinical education and to design action plans based on this research.

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

PubMed Central

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

2011-01-01

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

[Dermatology and skin color].

PubMed

Petit, Antoine

2010-09-01

Melanin is the pigment that is responsible for skin, hair and eye colours. Genetics and sun exposure are the two key factors that determine skin pigmentation. In dermatology, skin colours is significant, not only for semiology and diagnosis, but also for epidemiology and wounds healing.

Global Climate Change:A Monumental Mitigation Challenge

EPA Science Inventory

A holistic view of long-term sustainability cannot ignore humanity’s ever-growing demands on fossil fuels, water, and other finite geological resources. Figure 1 (Princiotta et. al., 2014) illustrates the key factors that are responsible for potentially unsustainable global impac...

Whole Body Plethysmography Reveals Differential Ventilatory Responses to Ozone in Rat Models of Cardiovascular Disease

EPA Science Inventory

Increasingly, urban air pollution is recognized as an important determinant of cardiovascular disease. Host susceptibility to air pollution can vary due to genetic predisposition and underlying disease. To elucidate key factors of host ...

Factors Released from Endothelial Cells Exposed to Flow Impact Adhesion, Proliferation, and Fate Choice in the Adult Neural Stem Cell Lineage.

PubMed

Dumont, Courtney M; Piselli, Jennifer M; Kazi, Nadeem; Bowman, Evan; Li, Guoyun; Linhardt, Robert J; Temple, Sally; Dai, Guohao; Thompson, Deanna M

2017-08-15

The microvasculature within the neural stem cell (NSC) niche promotes self-renewal and regulates lineage progression. Previous work identified endothelial-produced soluble factors as key regulators of neural progenitor cell (NPC) fate and proliferation; however, endothelial cells (ECs) are sensitive to local hemodynamics, and the effect of this key physiological process has not been defined. In this study, we evaluated adult mouse NPC response to soluble factors isolated from static or dynamic (flow) EC cultures. Endothelial factors generated under dynamic conditions significantly increased neuronal differentiation, while those released under static conditions stimulated oligodendrocyte differentiation. Flow increases EC release of neurogenic factors and of heparin sulfate glycosaminoglycans that increase their bioactivity, likely underlying the enhanced neuronal differentiation. Additionally, endothelial factors, especially from static conditions, promoted adherent growth. Together, our data suggest that blood flow may impact proliferation, adhesion, and the neuron-glial fate choice of adult NPCs, with implications for diseases and aging that reduce flow.

Determinants of ambulance response time: A study in Sabah, Malaysia

NASA Astrophysics Data System (ADS)

Chin, Su Na; Cheah, Phee Kheng; Arifin, Muhamad Yaakub; Wong, Boh Leng; Omar, Zaturrawiah; Yassin, Fouziah Md; Gabda, Darmesah

2017-04-01

Ambulance response time (ART) is one of the standard key performance indicators (KPI) in measuring the emergency medical services (EMS) delivery performances. When the mean time of ART of EMS system reaches the KPI target, it shows that the EMS system performs well. This paper considers the determinants of ART, using data sampled from 967 ambulance runs in a government hospital in Sabah. Multiple regression analysis with backward elimination was proposed for the identification of significant factors. Amongst the underlying factors, travel distance, age of patients, type of treatment and peak hours were identified to be significantly affecting ART. Identifying factors that influence ART helps the development of strategic improvement planning for reducing the ART.

Understanding key influencers' attitudes and beliefs about healthy public policy change for obesity prevention.

PubMed

Raine, Kim D; Nykiforuk, Candace I J; Vu-Nguyen, Karen; Nieuwendyk, Laura M; VanSpronsen, Eric; Reed, Shandy; Wild, T Cameron

2014-11-01

As overweight and obesity is a risk factor for chronic diseases, the development of environmental and healthy public policy interventions across multiple sectors has been identified as a key strategy to address this issue. In 2009, a survey was developed to assess the attitudes and beliefs regarding health promotion principles, and the priority and acceptability of policy actions to prevent obesity and chronic diseases, among key policy influencers in Alberta and Manitoba, Canada. Surveys were mailed to 1,765 key influencers from five settings: provincial government, municipal government, school boards, print media companies, and workplaces with greater than 500 employees. A total of 236 surveys were completed with a response rate of 15.0%. Findings indicate nearly unanimous influencer support for individual-focused policy approaches and high support for some environmental policies. Restrictive environmental and economic policies received weakest support. Obesity was comparable to smoking with respect to perceptions as a societal responsibility versus a personal responsibility, boding well for the potential of environmental policy interventions for obesity prevention. This level of influencer support provides a platform for more evidence to be brokered to policy influencers about the effectiveness of environmental policy approaches to obesity prevention. © 2014 The Obesity Society.

Meet the terminator: The phosphatase PP2A puts brakes on IRF-3 activation.

PubMed

Chattopadhyay, Saurabh; Sen, Ganes C

2014-04-24

Cellular interferon response to microbial infection is transient. In a recent paper in Immunity, Long et al. (2014) identify protein phosphatase 2A (PP2A) as a deactivator of phospho-interferon regulatory factor 3, the key transcription factor for interferon synthesis, thus providing one basis for the observed transiency. Copyright © 2014 Elsevier Inc. All rights reserved.

Understanding the key mechanisms of tropical forest responses to canopy loss and biomass deposition from experimental hurricane effects

Treesearch

A.B. Shiels; Grizelle Gonzalez

2014-01-01

To date, it is not clear which are the factors that most influence tropical forest recovery from hurricanes.Increased canopy openness and increased detritus (debris) deposition are two of the most likely factors,but due to their simultaneous occurrence during a hurricane, their relative effects cannot be separated without a manipulative experiment. Hence, in the...

Cognitive Abilities Explain Wording Effects in the Rosenberg Self-Esteem Scale.

PubMed

Gnambs, Timo; Schroeders, Ulrich

2017-12-01

There is consensus that the 10 items of the Rosenberg Self-Esteem Scale (RSES) reflect wording effects resulting from positively and negatively keyed items. The present study examined the effects of cognitive abilities on the factor structure of the RSES with a novel, nonparametric latent variable technique called local structural equation models. In a nationally representative German large-scale assessment including 12,437 students competing measurement models for the RSES were compared: a bifactor model with a common factor and a specific factor for all negatively worded items had an optimal fit. Local structural equation models showed that the unidimensionality of the scale increased with higher levels of reading competence and reasoning, while the proportion of variance attributed to the negatively keyed items declined. Wording effects on the factor structure of the RSES seem to represent a response style artifact associated with cognitive abilities.

Fibroblast growth factors: key players in regeneration and tissue repair.

PubMed

Maddaluno, Luigi; Urwyler, Corinne; Werner, Sabine

2017-11-15

Tissue injury initiates a complex repair process, which in some organisms can lead to the complete regeneration of a tissue. In mammals, however, the repair of most organs is imperfect and results in scar formation. Both regeneration and repair are orchestrated by a highly coordinated interplay of different growth factors and cytokines. Among the key players are the fibroblast growth factors (FGFs), which control the migration, proliferation, differentiation and survival of different cell types. In addition, FGFs influence the expression of other factors involved in the regenerative response. Here, we summarize current knowledge on the roles of endogenous FGFs in regeneration and repair in different organisms and in different tissues and organs. Gaining a better understanding of these FGF activities is important for appropriate modulation of FGF signaling after injury to prevent impaired healing and to promote organ regeneration in humans. © 2017. Published by The Company of Biologists Ltd.

Designing Iranian Model to Assess the Level of Health System Responsiveness.

PubMed

Askari, Roohollah; Arab, Mohammad; Rashidian, Arash; Akbari-Sari, Ali; Hosseini, Seyed Mostafa; Gharaee, Hojat

2016-03-01

Given the rapid pace of changes in community health needs and the mission of healthcare organizations to provide and promote the community's health, the growing need to increase health system responsiveness to people as a key element of observance and fulfillment of justice is felt more than ever. This study was aimed at designing the native model of responsiveness for Iran and to validate the aspects of the proposed model. Our study had a cross-sectional design and was a validation study performed in 2014. In order to define and identify responsiveness model aspects, the first phase recorded the views of 200 key informants from 19 provinces of Iran. Snowball sampling was used to select experts (based on WHO guideline). Then, the opinions of 18 comments were received from service recipients in the form of three focus group discussions and were analyzed by the frame framework analysis (interviewed recipients were selected using the purposive sampling method). Finally, in order to confirm the model's efficacy, a responsiveness questionnaire with 7 aspects (domains) and 52 indicators (items) obtained from the initial proposed model was answered by 600 members of the selected families in the two provinces of Fars and Yazd. A multi-stage cluster sampling approach was used for the household survey. The results were analyzed by the Confirmatory Factor Analysis (CFA) test and through the use of Lisrel software. Confirmatory Factor Analysis, based on the results of the key informant survey and group discussions, showed that according to quantities of GFI = 0.91, CFI = 0.93, NFI = 0.91, RMSEA = 0.074, SRMR = 0.061 and Hoelter (CN) = 178.54 in outpatient services and where GFI = 0.89, CFI = 0.91, NFI = 0.86, RMSEA = 0.064, SRMR = 0.053 and Hoelter (CN) = 158.93 for inpatient services, seven factors (F) (dignity, informed choice, confidentiality, patient training and informing, access to services, quality of basic amenities, and access to social support) are the main determinants of the responsiveness model and proposed model validity. Given the comprehensiveness of presented aspects and indicators in this proposed model and its validity test, the aforementioned responsiveness model can be considered a suitable model to use when assessing the levels of health system responsiveness in Iran.

Calcitonin protects chondrocytes from lipopolysaccharide-induced apoptosis and inflammatory response through MAPK/Wnt/NF-κB pathways.

PubMed

Zhang, Lai-Bo; Man, Zhen-Tao; Li, Wei; Zhang, Wei; Wang, Xian-Quan; Sun, Shui

2017-07-01

Calcitonin (CT) is an anti-absorbent, which has long been used for treatment of osteoporosis. However, little information is available about the effects of CT on osteoarthritis (OA). This study was mainly aimed to explore the effects of CT on the treatment of OA, as well as the underlying mechanisms. Chondrocytes were isolated from immature mice and then were incubated with lipopolysaccharide (LPS), CT, small interfering (si) RNA against bone morphogenetic protein (BMP)-2, and/or the inhibitors of MAPK/Wnt/NF-κB pathway. Thereafter, cell viability, apoptosis, nitric oxide (NO) and inflammatory factors productions, and expression levels of cartilage synthesis protein key factors, cartilage-derived morphogenetic protein (CDMP) 1, SRY (sex-determining region Y)-box 9 protein (SOX9), and MAPK/Wnt/NF-κB pathways key factors were determined. CT significantly reversed LPS-induced cell viability decrease, apoptosis increase, the inflammatory factors and NO secretion, the abnormally expression of cartilage synthesis proteins and the activation of MAPK/Wnt/NF-κB pathways (P<0.05). In addition, we observed that administration of the inhibitors of MAPK/Wnt/NF-κB pathways statistically further increased the levels of CDMP1 and SOX9 (P<0.05). Suppression of BMP-2 decreased the levels of CDMP1 and SOX9 and activated MAPK/Wnt/NF-κB pathways, and could partially abolish CT-modulated the expression changes in CDMP1 and SOX9, and MAPK/Wnt/NF-κB pathways key factors (P<0.05). The results showed that CT protects chondrocytes from LPS-induced apoptosis and inflammatory response by regulating BMP-2 and thus blocking MAPK/Wnt/NF-κB pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

Constrained Response Surface Optimisation and Taguchi Methods for Precisely Atomising Spraying Process

NASA Astrophysics Data System (ADS)

Luangpaiboon, P.; Suwankham, Y.; Homrossukon, S.

2010-10-01

This research presents a development of a design of experiment technique for quality improvement in automotive manufacturing industrial. The quality of interest is the colour shade, one of the key feature and exterior appearance for the vehicles. With low percentage of first time quality, the manufacturer has spent a lot of cost for repaired works as well as the longer production time. To permanently dissolve such problem, the precisely spraying condition should be optimized. Therefore, this work will apply the full factorial design, the multiple regression, the constrained response surface optimization methods or CRSOM, and Taguchi's method to investigate the significant factors and to determine the optimum factor level in order to improve the quality of paint shop. Firstly, 2κ full factorial was employed to study the effect of five factors including the paint flow rate at robot setting, the paint levelling agent, the paint pigment, the additive slow solvent, and non volatile solid at spraying of atomizing spraying machine. The response values of colour shade at 15 and 45 degrees were measured using spectrophotometer. Then the regression models of colour shade at both degrees were developed from the significant factors affecting each response. Consequently, both regression models were placed into the form of linear programming to maximize the colour shade subjected to 3 main factors including the pigment, the additive solvent and the flow rate. Finally, Taguchi's method was applied to determine the proper level of key variable factors to achieve the mean value target of colour shade. The factor of non volatile solid was found to be one more additional factor at this stage. Consequently, the proper level of all factors from both experiment design methods were used to set a confirmation experiment. It was found that the colour shades, both visual at 15 and 45 angel of measurement degrees of spectrophotometer, were nearly closed to the target and the defective at quality gate was also reduced from 0.35 WDPV to 0.10 WDPV. This reveals that the objective of this research is met and this procedure can be used as quality improvement guidance for paint shop of automotive vehicle.

Response and adaptation of photosynthesis, respiration, and antioxidant systems to elevated CO2 with environmental stress in plants

PubMed Central

Xu, Zhenzhu; Jiang, Yanling; Zhou, Guangsheng

2015-01-01

It is well known that plant photosynthesis and respiration are two fundamental and crucial physiological processes, while the critical role of the antioxidant system in response to abiotic factors is still a focus point for investigating physiological stress. Although one key metabolic process and its response to climatic change have already been reported and reviewed, an integrative review, including several biological processes at multiple scales, has not been well reported. The current review will present a synthesis focusing on the underlying mechanisms in the responses to elevated CO2 at multiple scales, including molecular, cellular, biochemical, physiological, and individual aspects, particularly, for these biological processes under elevated CO2 with other key abiotic stresses, such as heat, drought, and ozone pollution, as well as nitrogen limitation. The present comprehensive review may add timely and substantial information about the topic in recent studies, while it presents what has been well established in previous reviews. First, an outline of the critical biological processes, and an overview of their roles in environmental regulation, is presented. Second, the research advances with regard to the individual subtopics are reviewed, including the response and adaptation of the photosynthetic capacity, respiration, and antioxidant system to CO2 enrichment alone, and its combination with other climatic change factors. Finally, the potential applications for plant responses at various levels to climate change are discussed. The above issue is currently of crucial concern worldwide, and this review may help in a better understanding of how plants deal with elevated CO2 using other mainstream abiotic factors, including molecular, cellular, biochemical, physiological, and whole individual processes, and the better management of the ecological environment, climate change, and sustainable development. PMID:26442017

Helicopter pilots' views of air traffic controller responsibilities: a mismatch.

PubMed

Martin, Daniel; Nixon, Jim

2018-02-21

Controllers and pilots must work together to ensure safe and efficient helicopter flight within the London control zone. Subjective ratings of pilot perception of controller responsibility for five key flight tasks were obtained from thirty helicopter pilots. Three types of airspace were investigated. Results indicate that there is variation in pilot understanding of controller responsibility compared to the formal regulations that define controller responsibility. Significant differences in the perception of controller responsibility were found for the task of aircraft separation in class D airspace and along helicopter routes. Analysis of the patterns of response suggests that task type rather than the airspace type may be the key factor. Results are framed using the concept of a shared mental model. This research demonstrates that pilots flying in complex London airspace have an expectation of controller responsibility for certain flight tasks, in certain airspace types that is not supported by aviation regulation. Practitioner Summary: The responsibility for tasks during flight varies according to the flight rules used and airspace type. Helicopter pilots may attribute responsibility to controllers for tasks when controllers have no responsibility as defined by regulation. This variation between pilot perceptions of controller responsibility could affect safety within the London control zone.

MicroRNA-146a governs fibroblast activation and joint pathology in arthritis.

PubMed

Saferding, Victoria; Puchner, Antonia; Goncalves-Alves, Eliana; Hofmann, Melanie; Bonelli, Michael; Brunner, Julia S; Sahin, Emine; Niederreiter, Birgit; Hayer, Silvia; Kiener, Hans P; Einwallner, Elisa; Nehmar, Ramzi; Carapito, Raphael; Georgel, Philippe; Koenders, Marije I; Boldin, Mark; Schabbauer, Gernot; Kurowska-Stolarska, Mariola; Steiner, Günter; Smolen, Josef S; Redlich, Kurt; Blüml, Stephan

2017-08-01

Synovial fibroblasts are key cells orchestrating the inflammatory response in arthritis. Here we demonstrate that loss of miR-146a, a key epigenetic regulator of the innate immune response, leads to increased joint destruction in a TNF-driven model of arthritis by specifically regulating the behavior of synovial fibroblasts. Absence of miR-146a in synovial fibroblasts display a highly deregulated gene expression pattern and enhanced proliferation in vitro and in vivo. Deficiency of miR-146a induces deregulation of tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) in synovial fibroblasts, leading to increased proliferation. In addition, loss of miR-146a shifts the metabolic state of fibroblasts towards glycolysis and augments the ability of synovial fibroblasts to support the generation of osteoclasts by controlling the balance of osteoclastogenic regulatory factors receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). Bone marrow transplantation experiments confirmed the importance of miR-146a in the radioresistant mesenchymal compartment for the control of arthritis severity, in particular for inflammatory joint destruction. This study therefore identifies microRNA-146a as an important local epigenetic regulator of the inflammatory response in arthritis. It is a central element of an anti-inflammatory feedback loop in resident synovial fibroblasts, who are orchestrating the inflammatory response in chronic arthritis. MiR-146a restricts their activation, thereby preventing excessive tissue damage during arthritis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigation on the Success of Peasant Entrepreneurs

NASA Astrophysics Data System (ADS)

Li, Guohao; Wu, Bing; Bai, Guanglin

Peasant entrepreneurs are one important force to promote the development of new rural construction, so it has practical significance to study success factors of peasant entrepreneurs. 40 cases involving peasant entrepreneurs are studied through content analysis method and the results show that: (1) Making good use of existing resources in rural areas is a key factor for peasant entrepreneurs; (2) hard work, strong willness, tactics and courage, social responsibility are four most important success factors; (3) 23 items of success factor can be summarized into three categorized, personality traits, abilities, and behavior characteristics.

Control of regulatory T cell lineage commitment and maintenance.

PubMed

Josefowicz, Steven Z; Rudensky, Alexander

2009-05-01

Foxp3-expressing regulatory T (Treg) cells suppress pathology mediated by immune responses against self and foreign antigens and commensal microorganisms. Sustained expression of the transcription factor Foxp3, a key distinguishing feature of Treg cells, is required for their differentiation and suppressor function. In addition, Foxp3 expression prevents deviation of Treg cells into effector T cell lineages and confers dependence of Treg cell survival and expansion on growth factors, foremost interleukin-2, provided by activated effector T cells. In this review we discuss Treg cell differentiation and maintenance with a particular emphasis on molecular regulation of Foxp3 expression, arguably a key to mechanistic understanding of biology of regulatory T cells.

Optical methods for enabling focus cues in head-mounted displays for virtual and augmented reality

NASA Astrophysics Data System (ADS)

Hua, Hong

2017-05-01

Developing head-mounted displays (HMD) that offer uncompromised optical pathways to both digital and physical worlds without encumbrance and discomfort confronts many grand challenges, both from technological perspectives and human factors. Among the many challenges, minimizing visual discomfort is one of the key obstacles. One of the key contributing factors to visual discomfort is the lack of the ability to render proper focus cues in HMDs to stimulate natural eye accommodation responses, which leads to the well-known accommodation-convergence cue discrepancy problem. In this paper, I will provide a summary on the various optical methods approaches toward enabling focus cues in HMDs for both virtual reality (VR) and augmented reality (AR).

Drought planning and water allocation: an assessment of local capacity in Minnesota.

PubMed

Pirie, Rebecca L; de Loë, Rob C; Kreutzwiser, Reid

2004-10-01

Water allocation systems are challenged by hydrologic droughts, which reduce available water supplies and can adversely affect human and environmental systems. To address this problem, drought management mechanisms have been instituted in jurisdictions around the world. Historically, these mechanisms have involved a crisis management or reactive approach. An important trend during the past decade in places such as the United States has been a shift to a more proactive approach, emphasizing drought preparedness and local involvement. Unfortunately, local capacity for drought planning is highly variable, with some local governments and organizations proving to be more capable than others of taking on new responsibilities. This paper reports on a study of drought planning and water allocation in the State of Minnesota. Factors facilitating and constraining local capacity for drought planning were identified using in-depth key informant interviews with state officials and members of two small Minnesota cities, combined with an analysis of pertinent documentation. A key factor contributing to the effectiveness of Minnesota's system is a water allocation system with explicit priorities during shortages, and provisions for restrictions. At the same time, the requirement that water suppliers create Public Water Supply Emergency Conservation Plans (PWSECP) clarifies the roles and responsibilities of key local actors. Unfortunately, the research revealed that mandated PWSECP are not always implemented, and that awareness of drought and drought planning measures in general may be poor at the local level. From the perspective of the two cities evaluated, factors that contributed to local capacity included sound financial and human resources, and (in some cases) effective vertical and horizontal linkages. This analysis of experiences in Minnesota highlights problems that can occur when senior governments establish policy frameworks that increase responsibilities at the local level without also addressing local capacity.

Factor D Enzyme

NASA Technical Reports Server (NTRS)

2004-01-01

The trauma caused by the open heart surgery often triggers massive inflammation because the immune system overreacts. Factor D, the protein which plays a key role in the biological steps that activate this immune response prevents the imune system from inappropriately rurning out of control, allowing the patient to recover more rapidly. Factor D blockers, with their great potential to alleviate the complication of inflammation associated with heart surgery, are now being developed for clinical trials. These new drugs, developed from space research, should be commercially available as soon as year 2001.

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

PubMed Central

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

2000-01-01

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

Risk Factors and Therapeutic Targets in Pancreatic Cancer

PubMed Central

Wörmann, Sonja Maria; Algül, Hana

2013-01-01

Pancreatic cancer (PC) is one of the most challenging tumor entities worldwide, characterized as a highly aggressive disease with dismal overall prognosis and an incidence rate equalling mortality rate. Over the last decade, substantial progress has been made to define the morphological changes and key genetic events in pancreatic carcinogenesis. And yet, it is still unclear what factors trigger PC. Some risk factors appear to be associated with sex, age, race/ethnicity, or other rare genetic conditions. Additionally, modifying factors such as smoking, obesity, diabetes, occupational risk factors, etc., increase the potential for acquiring genetic mutations that may result in PC. Another hallmark of PC is its poor response to radio- and chemo-therapy. Current chemotherapeutic regimens could not provide substantial survival benefit with a clear increase in overall survival. Recently, several new approaches to significantly improve the clinical outcome of PC have been described involving downstream signaling cascades desmoplasia and stromal response as well as tumor microenvironment, immune response, vasculature, and angiogenesis. This review summarizes major risk factors for PC and tries to illuminate relevant targets considerable for new therapeutic approaches. PMID:24303367

Zinc in Infection and Inflammation

PubMed Central

Gammoh, Nour Zahi; Rink, Lothar

2017-01-01

Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli. PMID:28629136

Zinc in Infection and Inflammation.

PubMed

Gammoh, Nour Zahi; Rink, Lothar

2017-06-17

Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

[Medicines interacting with mitochondria: anti-ischemic effects of trimetazidine].

PubMed

Spedding, M; Tillement, J P; Morin, D; Le Ridant, A

1999-01-01

While mitochondria are key factors in energy production in cells they are also key factors in their life cycle because under certain circumstances they can provoke cellular apoptosis. Some 45 per cent of myocardial volume is taken up by mitochondria. Furthermore, mitochondria are key to many aspects of neuronal activity and can trigger neurodegenerative processes. Lipid oxidation is responsible for the production of much ATP resynthesis in the heart but this process is less oxygen efficient than glucose oxidation. During ischaemia, lipid oxidation is suddenly blocked, but markedly increased during reperfusion, causing accumulation of potentially toxic metabolites (acylcarnitines, acyl-CoA, lysophospholipids). These metabolites can change calcium handling, inducing arrhythmias. Trimetazidine, and another product in development, ranolazine, by inhibiting lipid oxidation favours glucose oxidation and inhibits the production of deleterious lipid metabolites. Thus this class of drugs can have beneficial effects on myocardial metabolism without direct haemodynamic effects.

Improved Training Method for Rapid Rehabilitation of Amputees

DTIC Science & Technology

2013-03-01

crowded environments, stairs , ramps, and hills. The key factor that limits the ability of amputees to achieve maximum functional capabilities is falls...Method for evoking a trip response using a treadmill based perturbation during locomotion”, has been submitted to the Journal of Biomechanics o

A Transcriptional Regulatory Switch Underlying B-Cell Terminal Differentiation and its Disruption by Dioxin

EPA Science Inventory

The terminal differentiation of B lymphocytes into antibody-secreting plasma cells upon antigen stimulation is a crucial step in the humoral immune response. The mutually-repressive interactions among three key regulatory transcription factors underlying B to plasma cell differe...

Executive Development: Key Factors for Success.

ERIC Educational Resources Information Center

Fenwick-Magrath, Julie A.

1988-01-01

Reports results from a survey of 12 leading corporations concerning their management of the executive development process. Indicates that involvement of the chief executive officer, a clear policy, a relationship between executive development and business strategies and objectives, annual succession planning, and management responsibility are key…

The fourth dimension in immunological space: how the struggle for nutrients selects high-affinity lymphocytes.

PubMed

Wensveen, Felix M; van Gisbergen, Klaas P J M; Eldering, Eric

2012-09-01

Lymphocyte activation via the antigen receptor is associated with radical shifts in metabolism and changes in requirements for nutrients and cytokines. Concomitantly, drastic changes occur in the expression of pro-and anti-apoptotic proteins that alter the sensitivity of lymphocytes to limiting concentrations of key survival factors. Antigen affinity is a primary determinant for the capacity of activated lymphocytes to access these vital resources. The shift in metabolic needs and the variable access to key survival factors is used by the immune system to eliminate activated low-affinity cells and to generate an optimal high-affinity response. In this review, we focus on the control of apoptosis regulators in activated lymphocytes by nutrients, cytokines, and costimulation. We propose that the struggle among individual clones that leads to the formation of high-affinity effector cell populations is in effect an 'invisible' fourth signal required for effective immune responses. © 2012 John Wiley & Sons A/S.

Uncontrolled eating in adolescents: The role of impulsivity and automatic approach bias for food.

PubMed

Booth, Charlotte; Spronk, Desiree; Grol, Maud; Fox, Elaine

2018-01-01

Obesity is a global problem reaching epidemic proportions and can be explained by unhealthy eating and sedentary lifestyles. Understanding the psychological processes underlying unhealthy eating behaviour is crucial for the development of effective obesity prevention programmes. Dual-process models implicate the interplay between impaired cognitive control and enhanced automatic responsivity to rewarding food cues as key risk factors. The current study assessed the influence of four different components of trait impulsivity (reflecting impaired cognitive control) and automatic approach bias for food (reflecting automatic responsivity to food) on uncontrolled eating in a large sample (N = 504) of young adolescents. Of the four impulsivity factors, negative urgency was found to be the strongest predictor of uncontrolled eating. Interestingly, we found that lack of premeditation was a key risk factor for uncontrolled eating, but only when approach bias for food was high, supporting a dual-process model. Lack of perseverance showed a similar interactive pattern to a lesser degree and sensation-seeking did not predict uncontrolled eating. Together, our results show that distinct components of trait impulsivity are differentially associated with uncontrolled eating behaviour in adolescents, and that automatic processing of food cues may be an important factor in modulating this relationship. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways.

PubMed

Plantier, Laurent; Renaud, Hélène; Respaud, Renaud; Marchand-Adam, Sylvain; Crestani, Bruno

2016-12-13

Heritable profibrotic differentiation of lung fibroblasts is a key mechanism of idiopathic pulmonary fibrosis (IPF). Its mechanisms are yet to be fully understood. In this study, individual data from four independent microarray studies comparing the transcriptome of fibroblasts cultured in vitro from normal (total n = 20) and IPF (total n = 20) human lung were compiled for meta-analysis following normalization to z-scores. One hundred and thirteen transcripts were upregulated and 115 were downregulated in IPF fibroblasts using the Significance Analysis of Microrrays algorithm with a false discovery rate of 5%. Downregulated genes were highly enriched for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional classes related to inflammation and immunity such as Defense response to virus, Influenza A, tumor necrosis factor (TNF) mediated signaling pathway, interferon-inducible absent in melanoma2 (AIM2) inflammasome as well as Apoptosis. Although upregulated genes were not enriched for any functional class, select factors known to play key roles in lung fibrogenesis were overexpressed in IPF fibroblasts, most notably connective tissue growth factor ( CTGF ) and serum response factor ( SRF ), supporting their role as drivers of IPF. The full data table is available as a supplement.

Phenylalanine Is Required to Promote Specific Developmental Responses and Prevents Cellular Damage in Response to Ultraviolet Light in Soybean (Glycine max) during the Seed-to-Seedling Transition

PubMed Central

Sullivan, Joe H.; Muhammad, DurreShahwar; Warpeha, Katherine M.

2014-01-01

UV-radiation elicits a suite of developmental (photomorphogenic) and protective responses in plants, but responses early post-germination have received little attention, particularly in intensively bred plants of economic importance. We examined germination, hypocotyl elongation, leaf pubescence and subcellular responses of germinating and/or etiolated soybean (Glycine max (L.) Merr.) seedlings in response to treatment with discrete wavelengths of UV-A or UV-B radiation. We demonstrate differential responses of germinating/young soybean seedlings to a range of UV wavelengths that indicate unique signal transduction mechanisms regulate UV-initiated responses. We have investigated how phenylalanine, a key substrate in the phenylpropanoid pathway, may be involved in these responses. Pubescence may be a key location for phenylalanine-derived protective compounds, as UV-B irradiation increased pubescence and accumulation of UV-absorbing compounds within primary leaf pubescence, visualized by microscopy and absorbance spectra. Mass spectrometry analysis of pubescence indicated that sinapic esters accumulate in the UV-irradiated hairs compared to unirradiated primary leaf tissue. Deleterious effects of some UV-B wavelengths on germination and seedling responses were reduced or entirely prevented by inclusion of phenylalanine in the growth media. Key effects of phenylalanine were not duplicated by tyrosine or tryptophan or sucrose, nor is the specificity of response due to the absorbance of phenylalanine itself. These results suggest that in the seed-to-seedling transition, phenylalanine may be a limiting factor in the development of initial mechanisms of UV protection in the developing leaf. PMID:25549094

The Role of Tomato WRKY Genes in Plant Responses to Combined Abiotic and Biotic Stresses

PubMed Central

Bai, Yuling; Sunarti, Sri; Kissoudis, Christos; Visser, Richard G. F.; van der Linden, C. G.

2018-01-01

In the field, plants constantly face a plethora of abiotic and biotic stresses that can impart detrimental effects on plants. In response to multiple stresses, plants can rapidly reprogram their transcriptome through a tightly regulated and highly dynamic regulatory network where WRKY transcription factors can act as activators or repressors. WRKY transcription factors have diverse biological functions in plants, but most notably are key players in plant responses to biotic and abiotic stresses. In tomato there are 83 WRKY genes identified. Here we review recent progress on functions of these tomato WRKY genes and their homologs in other plant species, such as Arabidopsis and rice, with a special focus on their involvement in responses to abiotic and biotic stresses. In particular, we highlight WRKY genes that play a role in plant responses to a combination of abiotic and biotic stresses.

PKC-Theta is a Novel SC35 Splicing Factor Regulator in Response to T Cell Activation.

PubMed

McCuaig, Robert Duncan; Dunn, Jennifer; Li, Jasmine; Masch, Antonia; Knaute, Tobias; Schutkowski, Mike; Zerweck, Johannes; Rao, Sudha

2015-01-01

Alternative splicing of nuclear pre-mRNA is essential for generating protein diversity and regulating gene expression. While many immunologically relevant genes undergo alternative splicing, the role of regulated splicing in T cell immune responses is largely unexplored, and the signaling pathways and splicing factors that regulate alternative splicing in T cells are poorly defined. Here, we show using a combination of Jurkat T cells, human primary T cells, and ex vivo naïve and effector virus-specific T cells isolated after influenza A virus infection that SC35 phosphorylation is induced in response to stimulatory signals. We show that SC35 colocalizes with RNA polymerase II in activated T cells and spatially overlaps with H3K27ac and H3K4me3, which mark transcriptionally active genes. Interestingly, SC35 remains coupled to the active histone marks in the absence of continuing stimulatory signals. We show for the first time that nuclear PKC-θ co-exists with SC35 in the context of the chromatin template and is a key regulator of SC35 in T cells, directly phosphorylating SC35 peptide residues at RNA recognition motif and RS domains. Collectively, our findings suggest that nuclear PKC-θ is a novel regulator of the key splicing factor SC35 in T cells.

Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation.

PubMed

Papaspyridonos, Marianna; Matei, Irina; Huang, Yujie; do Rosario Andre, Maria; Brazier-Mitouart, Helene; Waite, Janelle C; Chan, April S; Kalter, Julie; Ramos, Ilyssa; Wu, Qi; Williams, Caitlin; Wolchok, Jedd D; Chapman, Paul B; Peinado, Hector; Anandasabapathy, Niroshana; Ocean, Allyson J; Kaplan, Rosandra N; Greenfield, Jeffrey P; Bromberg, Jacqueline; Skokos, Dimitris; Lyden, David

2015-04-29

A central mechanism of tumour progression and metastasis involves the generation of an immunosuppressive 'macroenvironment' mediated in part through tumour-secreted factors. Here we demonstrate that upregulation of the Inhibitor of Differentiation 1 (Id1), in response to tumour-derived factors, such as TGFβ, is responsible for the switch from dendritic cell (DC) differentiation to myeloid-derived suppressor cell expansion during tumour progression. Genetic inactivation of Id1 largely corrects the myeloid imbalance, whereas Id1 overexpression in the absence of tumour-derived factors re-creates it. Id1 overexpression leads to systemic immunosuppression by downregulation of key molecules involved in DC differentiation and suppression of CD8 T-cell proliferation, thus promoting primary tumour growth and metastatic progression. Furthermore, advanced melanoma patients have increased plasma TGFβ levels and express higher levels of ID1 in myeloid peripheral blood cells. This study reveals a critical role for Id1 in suppressing the anti-tumour immune response during tumour progression and metastasis.

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.

Inflammatory Mechanisms and Oxidative Stress as Key Factors Responsible for Progression of Neurodegeneration: Role of Brain Innate Immune System.

PubMed

Leszek, Jerzy; Barreto, George E; Gąsiorowski, Kazimierz; Koutsouraki, Euphrosyni; Ávila-Rodrigues, Marco; Aliev, Gjumrakch

2016-01-01

Chronic inflammation is characterized by longstanding microglial activation followed by sustained release of inflammatory mediators, which aid in enhanced nitrosative and oxidative stress. The sustained release of inflammatory mediators propels the inflammatory cycle by increased microglial activation, promoting their proliferation and thus stimulating enhanced release of inflammatory factors. Elevated levels of several cytokines and chronic neuroinflammation have been associated with many neurodegenerative disorders of central nervous system like age-related macular degeneration, Alzheimer disease, multiple sclerosis, Parkinson's disease, Huntington' disease, and tauopathies. This review highlights the basic mechanisms of neuroinflammation, the characteristics of neurodegenerative diseases, and the main immunologic responses in CNS neurodegenerative disorders. A comprehensive outline for the crucial role of microglia in neuroinflammation and neurodegeneration and the role of Toll-like receptor signalling in coexistence of inflammatory mechanisms and oxidative stress as major factors responsible for progression of neurodegeneration have also been presented.

From Metabonomics to Pharmacometabonomics: The Role of Metabolic Profiling in Personalized Medicine

PubMed Central

Everett, Jeremy R.

2016-01-01

Variable patient responses to drugs are a key issue for medicine and for drug discovery and development. Personalized medicine, that is the selection of medicines for subgroups of patients so as to maximize drug efficacy and minimize toxicity, is a key goal of twenty-first century healthcare. Currently, most personalized medicine paradigms rely on clinical judgment based on the patient's history, and on the analysis of the patients' genome to predict drug effects i.e., pharmacogenomics. However, variability in patient responses to drugs is dependent upon many environmental factors to which human genomics is essentially blind. A new paradigm for predicting drug responses based on individual pre-dose metabolite profiles has emerged in the past decade: pharmacometabonomics, which is defined as “the prediction of the outcome (for example, efficacy or toxicity) of a drug or xenobiotic intervention in an individual based on a mathematical model of pre-intervention metabolite signatures.” The new pharmacometabonomics paradigm is complementary to pharmacogenomics but has the advantage of being sensitive to environmental as well as genomic factors. This review will chart the discovery and development of pharmacometabonomics, and provide examples of its current utility and possible future developments. PMID:27660611

Supervisors' views on employer responsibility in the return to work process. A focus group study.

PubMed

Holmgren, Kristina; Dahlin Ivanoff, Synneve; Ivanoff, Synneve Dahlin

2007-03-01

Supervisors' attitudes and measures have been pointed out by employees to influence the return to work process. The purpose of this study was to explore supervisors' views on employer responsibility in the return to work process and factors influencing the support of sick-listed employees. The focus group method was used. Six groups were conducted and each group met on one occasion. Twenty-three supervisors experienced in managing sick-listed employees participated. Two different themes emerged; In "The Supervisor is the Key Person" the participants found themselves as being key persons, carrying the main responsibility for the rehabilitation of the sick-listed employees and for creating a good working environment, thus preventing ill health and sick-listing among the employees. In the second theme "Influential Factors in Rehabilitation Work" the participants described the rehabilitation work as a part of a greater whole influenced by society, demands and resources of the workplace and the interplay between all parties involved. The study gives us the supervisors' perspective on the complexity of the return to work rehabilitation. This knowledge could be invaluable and be used to improve the possibilities for developing successful collaboration in occupational rehabilitation.

Mechanisms that Trigger a Good Health-Care Response to Intimate Partner Violence in Spain. Combining Realist Evaluation and Qualitative Comparative Analysis Approaches.

PubMed

Goicolea, Isabel; Vives-Cases, Carmen; Hurtig, Anna-Karin; Marchal, Bruno; Briones-Vozmediano, Erica; Otero-García, Laura; García-Quinto, Marta; San Sebastian, Miguel

2015-01-01

Health care professionals, especially those working in primary health-care services, can play a key role in preventing and responding to intimate partner violence. However, there are huge variations in the way health care professionals and primary health care teams respond to intimate partner violence. In this study we tested a previously developed programme theory on 15 primary health care center teams located in four different Spanish regions: Murcia, C Valenciana, Castilla-León and Cantabria. The aim was to identify the key combinations of contextual factors and mechanisms that trigger a good primary health care center team response to intimate partner violence. A multiple case-study design was used. Qualitative and quantitative information was collected from each of the 15 centers (cases). In order to handle the large amount of information without losing familiarity with each case, qualitative comparative analysis was undertaken. Conditions (context and mechanisms) and outcomes, were identified and assessed for each of the 15 cases, and solution formulae were calculated using qualitative comparative analysis software. The emerging programme theory highlighted the importance of the combination of each team's self-efficacy, perceived preparation and women-centredness in generating a good team response to intimate partner violence. The use of the protocol and accumulated experience in primary health care were the most relevant contextual/intervention conditions to trigger a good response. However in order to achieve this, they must be combined with other conditions, such as an enabling team climate, having a champion social worker and having staff with training in intimate partner violence. Interventions to improve primary health care teams' response to intimate partner violence should focus on strengthening team's self-efficacy, perceived preparation and the implementation of a woman-centred approach. The use of the protocol combined with a large working experience in primary health care, and other factors such as training, a good team climate, and having a champion social worker on the team, also played a key role. Measures to sustain such interventions and promote these contextual factors should be encouraged.

TIME FOR COFFEE Represses Accumulation of the MYC2 Transcription Factor to Provide Time-of-Day Regulation of Jasmonate Signaling in Arabidopsis[C][W][OA

PubMed Central

Shin, Jieun; Heidrich, Katharina; Sanchez-Villarreal, Alfredo; Parker, Jane E.; Davis, Seth J.

2012-01-01

Plants are confronted with predictable daily biotic and abiotic stresses that result from the day–night cycle. The circadian clock provides an anticipation mechanism to respond to these daily stress signals to increase fitness. Jasmonate (JA) is a phytohormone that mediates various growth and stress responses. Here, we found that the circadian-clock component TIME FOR COFFEE (TIC) acts as a negative factor in the JA-signaling pathway. We showed that the tic mutant is hypersensitive to growth-repressive effects of JA and displays altered JA-regulated gene expression. TIC was found to interact with MYC2, a key transcription factor of JA signaling. From this, we discovered that the circadian clock rhythmically regulates JA signaling. TIC is a key determinant in this circadian-gated process, and as a result, the tic mutant is defective in rhythmic JA responses to pathogen infection. TIC acts here by inhibiting MYC2 protein accumulation and by controlling the transcriptional repression of CORONATINE INSENSITIVE1 in an evening-phase–specific manner. Taken together, we propose that TIC acts as an output component of the circadian oscillator to influence JA signaling directly. PMID:22693280

Development of Integrated Magnetic and Kinetic Control-oriented Transport Model for q-profile Response Prediction in EAST Discharges

NASA Astrophysics Data System (ADS)

Wang, Hexiang; Schuster, Eugenio; Rafiq, Tariq; Kritz, Arnold; Ding, Siye

2016-10-01

Extensive research has been conducted to find high-performance operating scenarios characterized by high fusion gain, good confinement, plasma stability and possible steady-state operation. A key plasma property that is related to both the stability and performance of these advanced plasma scenarios is the safety factor profile. A key component of the EAST research program is the exploration of non-inductively driven steady-state plasmas with the recently upgraded heating and current drive capabilities that include lower hybrid current drive and neutral beam injection. Anticipating the need for tight regulation of the safety factor profile in these plasma scenarios, a first-principles-driven (FPD)control-oriented model is proposed to describe the safety factor profile evolution in EAST in response to the different actuators. The TRANSP simulation code is employed to tailor the FPD model to the EAST tokamak geometry and to convert it into a form suitable for control design. The FPD control-oriented model's prediction capabilities are demonstrated by comparing predictions with experimental data from EAST. Supported by the US DOE under DE-SC0010537,DE-FG02-92ER54141 and DE-SC0013977.

The Principal: Leadership for the Effective and Productive School.

ERIC Educational Resources Information Center

Bookbinder, Robert M.

This book synthesizes research findings on principal effectiveness, viewing the principal as a key factor in ensuring school effectiveness and productivity. Methodology includes an extensive literature review, participation and observation grounded in theory, and pragmatic responses to conditions and issues. Chapter 1 presents an overview of…

Sustaining Arts Programs in Public Education

ERIC Educational Resources Information Center

Dunstan, David

2016-01-01

The purpose of this qualitative research case study was to investigate leadership and funding decisions that determine key factors responsible for sustaining arts programs in public schools. While the educational climate, financial constraints, and standardized testing continue to impact arts programs in public education, Eastland High School, the…

A Comprehensive Transcriptomic and Proteomic Analysis of Hydra Head Regeneration

PubMed Central

Petersen, Hendrik O.; Höger, Stefanie K.; Looso, Mario; Lengfeld, Tobias; Kuhn, Anne; Warnken, Uwe; Nishimiya-Fujisawa, Chiemi; Schnölzer, Martina; Krüger, Marcus; Özbek, Suat; Simakov, Oleg; Holstein, Thomas W.

2015-01-01

The cnidarian freshwater polyp Hydra sp. exhibits an unparalleled regeneration capacity in the animal kingdom. Using an integrative transcriptomic and stable isotope labeling by amino acids in cell culture proteomic/phosphoproteomic approach, we studied stem cell-based regeneration in Hydra polyps. As major contributors to head regeneration, we identified diverse signaling pathways adopted for the regeneration response as well as enriched novel genes. Our global analysis reveals two distinct molecular cascades: an early injury response and a subsequent, signaling driven patterning of the regenerating tissue. A key factor of the initial injury response is a general stabilization of proteins and a net upregulation of transcripts, which is followed by a subsequent activation cascade of signaling molecules including Wnts and transforming growth factor (TGF) beta-related factors. We observed moderate overlap between the factors contributing to proteomic and transcriptomic responses suggesting a decoupled regulation between the transcriptional and translational levels. Our data also indicate that interstitial stem cells and their derivatives (e.g., neurons) have no major role in Hydra head regeneration. Remarkably, we found an enrichment of evolutionarily more recent genes in the early regeneration response, whereas conserved genes are more enriched in the late phase. In addition, genes specific to the early injury response were enriched in transposon insertions. Genetic dynamicity and taxon-specific factors might therefore play a hitherto underestimated role in Hydra regeneration. PMID:25841488

Factors affecting the innovative practice of nurse managers in health organisations.

PubMed

Williams, Lindy; McMurray, Adela J

This exploratory study reports on two surveys conducted in metropolitan and rural health organisations. Two questionnaires consisting of open and closed questions were distributed to a total of 340 respondents resulting in 176 usable responses, yielding a response rate of 53%. The findings revealed that nurse managers require fairness, trust, recognition, supervisory encouragement, organisational support, and reward for efforts. These are key aspects of organisational climate, which support innovative practice. Experience and innovation were significantly related and other factors such as, management structures and management styles, also had an impact on nurse managers' ability to exhibit innovative behaviour in the 21st Century workplace.

Immune function trade-offs in response to parasite threats.

PubMed

Kirschman, Lucas J; Quade, Adam H; Zera, Anthony J; Warne, Robin W

2017-04-01

Immune function is often involved in physiological trade-offs because of the energetic costs of maintaining constitutive immunity and mounting responses to infection. However, immune function is a collection of discrete immunity factors and animals should allocate towards factors that combat the parasite threat with the highest fitness cost. For example, animals on dispersal fronts of expanding population may be released from density-dependent diseases. The costs of immunity, however, and life history trade-offs in general, are often context dependent. Trade-offs are often most apparent under conditions of unusually limited resources or when animals are particularly stressed, because the stress response can shift priorities. In this study we tested how humoral and cellular immune factors vary between phenotypes of a wing dimorphic cricket and how physiological stress influences these immune factors. We measured constitutive lysozyme activity, a humoral immune factor, and encapsulation response, a cellular immune factor. We also stressed the crickets with a sham predator in a full factorial design. We found that immune strategy could be explained by the selective pressures encountered by each morph and that stress decreased encapsulation, but not lysozyme activity. These results suggest a possible trade-off between humoral and cellular immunity. Given limited resources and the expense of immune factors, parasite pressures could play a key factor in maintaining insect polyphenism via disruptive selection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multi-Omics and Integrated Network Analyses Reveal New Insights into the Systems Relationships between Metabolites, Structural Genes, and Transcriptional Regulators in Developing Grape Berries (Vitis vinifera L.) Exposed to Water Deficit.

PubMed

Savoi, Stefania; Wong, Darren C J; Degu, Asfaw; Herrera, Jose C; Bucchetti, Barbara; Peterlunger, Enrico; Fait, Aaron; Mattivi, Fulvio; Castellarin, Simone D

2017-01-01

Grapes are one of the major fruit crops and they are cultivated in many dry environments. This study comprehensively characterizes the metabolic response of grape berries exposed to water deficit at different developmental stages. Increases of proline, branched-chain amino acids, phenylpropanoids, anthocyanins, and free volatile organic compounds have been previously observed in grape berries exposed to water deficit. Integrating RNA-sequencing analysis of the transcriptome with large-scale analysis of central and specialized metabolites, we reveal that these increases occur via a coordinated regulation of key structural pathway genes. Water deficit-induced up-regulation of flavonoid genes is also coordinated with the down-regulation of many stilbene synthases and a consistent decrease in stilbenoid concentration. Water deficit activated both ABA-dependent and ABA-independent signal transduction pathways by modulating the expression of several transcription factors. Gene-gene and gene-metabolite network analyses showed that water deficit-responsive transcription factors such as bZIPs, AP2/ERFs, MYBs, and NACs are implicated in the regulation of stress-responsive metabolites. Enrichment of known and novel cis -regulatory elements in the promoters of several ripening-specific/water deficit-induced modules further affirms the involvement of a transcription factor cross-talk in the berry response to water deficit. Together, our integrated approaches show that water deficit-regulated gene modules are strongly linked to key fruit-quality metabolites and multiple signal transduction pathways may be critical to achieve a balance between the regulation of the stress-response and the berry ripening program. This study constitutes an invaluable resource for future discoveries and comparative studies, in grapes and other fruits, centered on reproductive tissue metabolism under abiotic stress.

EFFECTS OF TITANIUM DIOXIDE NANOPARTICLE EXPOSURE ON NEUROIMMUNE RESPONSES IN RAT AIRWAYS

PubMed Central

Scuri, Mario; Chen, Bean T.; Castranova, Vincent; Reynolds, Jeffrey S.; Johnson, Victor J.; Samsell, Lennie; Walton, Cheryl; Piedimonte, Giovanni

2013-01-01

Exposure to ambient nanoparticles (defined as particulate matter [PM] having one dimension < 100 nm) is associated with increased risk of childhood and adult asthma. Nanomaterials feature a smaller aerodynamic diameter and a higher surface area per unit mass ratio compared to fine or coarse-sized particles, resulting in greater lung deposition efficiency and an increased potential for biological interaction. The neurotrophins nerve growth factor and brain-derived neurotrophic factor are key regulatory elements of neuronal development and responsiveness of airway sensory neurons. Changes in their expression are associated with bronchoconstriction, airway hyperresponsiveness, and airway inflammation. The neurogenic-mediated control of airway responses is a key pathophysiological mechanism of childhood asthma. However, the effects of nanoparticle exposure on neurotrophin-driven airway responses and their potential role as a predisposing factor for developing asthma have not been clearly elucidated. In this study, in vivo inhalation exposure to titanium dioxide nanoparticles (12 mg/m13; 5.6 h/d for 3 d) produced upregulation of lung neurotrophins in weanling (2-wk-old) and newborn (2-d-old) rats but not in adult (12-wk-old) animals compared to controls. This effect was associated with increased airway responsiveness and upregulation of growth-related oncogene/keratine-derived chemokine (GRO/KC; CXCL1, rat equivalent of human interleukin [IL]-8) in bronchoalveolar lavage fluid. These data show for the first time that exposure to nanoparticulate upregulates the expression of lung neurotrophins in an age-dependent fashion and that this effect is associated with airway hyperresponsiveness and inflammation. These results suggest the presence of a critical window of vulnerability in earlier stages of lung development, which may lead to a higher risk of developing asthma. PMID:20818535

Explicit Consideration of Baseline Factors to Assess Recombinant Tissue-Type Plasminogen Activator Response With Respect to Race and Sex

PubMed Central

Mandava, Pitchaiah; Murthy, Santosh B.; Munoz, Melody; McGuire, Dawn; Simon, Roger P.; Alexandrov, Andrei V.; Albright, Karen C.; Boehme, Amelia K.; Martin-Schild, Sheryl; Martini, Sharyl; Kent, Thomas A.

2017-01-01

Background and Purpose Sex and race reportedly influence outcome after recombinant tissue-type plasminogen activator (rtPA). It is, however, unclear whether baseline imbalances (eg, stroke severity) or lack of response to thrombolysis is responsible. We applied balancing methods to test the hypothesis that race and sex influence outcome after rtPA independent of baseline conditions. Methods We mapped group outcomes from the National Institute of Neurological Disorders and Stroke (NINDS) dataset based on race and sex onto a surrogate-control function to assess differences from expected outcomes at their respective National Institutes of Health Stroke Scale and age. Outcomes were also compared for subjects matched individually on key baseline factors using NINDS and 2 recent datasets from southeastern United States. Results At similar National Institutes of Health Stroke Scale and age, 90-day good outcomes (modified Rankin Score, 0–2) in NINDS were similarly improved after rtPA for white men and women. There was a strong trend for improvement in black men. Conversely, black women treated with rtPA showed response rates no different from the controls. After baseline matching, there were nonsignificant trends in outcomes except for significantly fewer good outcomes in black versus matched white women (37% versus 63%; P=0.027). Pooling the 3 datasets showed a similar trend for poorer short-term outcome for black women (P=0.054; modified Rankin Score, 0–1). Conclusions Matching for key baseline factors indicated that race and sex influence outcome most strikingly in black women who demonstrated poorest outcomes after rtPA. This finding supports the hypothesis that poor response to rtPA, rather than differences in baseline conditions, contributes to the worse outcome. This finding requires prospective confirmation. PMID:23674524

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.

Activating transcription factor 3 promotes loss of the acinar cell phenotype in response to cerulein-induced pancreatitis in mice.

PubMed

Fazio, Elena N; Young, Claire C; Toma, Jelena; Levy, Michael; Berger, Kurt R; Johnson, Charis L; Mehmood, Rashid; Swan, Patrick; Chu, Alphonse; Cregan, Sean P; Dilworth, F Jeffrey; Howlett, Christopher J; Pin, Christopher L

2017-09-01

Pancreatitis is a debilitating disease of the exocrine pancreas that, under chronic conditions, is a major susceptibility factor for pancreatic ductal adenocarcinoma (PDAC). Although down-regulation of genes that promote the mature acinar cell fate is required to reduce injury associated with pancreatitis, the factors that promote this repression are unknown. Activating transcription factor 3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly activated during pancreatic insult. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that ATF3 is bound to the transcriptional regulatory regions of >30% of differentially expressed genes during the initiation of pancreatitis. Of importance, ATF3-dependent regulation of these genes was observed only upon induction of pancreatitis, with pathways involved in inflammation, acinar cell differentiation, and cell junctions being specifically targeted. Characterizing expression of transcription factors that affect acinar cell differentiation suggested that acinar cells lacking ATF3 maintain a mature cell phenotype during pancreatitis, a finding supported by maintenance of junctional proteins and polarity markers. As a result, Atf3 -/- pancreatic tissue displayed increased tissue damage and inflammatory cell infiltration at early time points during injury but, at later time points, showed reduced acinar-to-duct cell metaplasia. Thus our results reveal a critical role for ATF3 as a key regulator of the acinar cell transcriptional response during injury and may provide a link between chronic pancreatitis and PDAC. © 2017 Fazio et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

The transcriptional regulatory network in the drought response and its crosstalk in abiotic stress responses including drought, cold, and heat.

PubMed

Nakashima, Kazuo; Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

2014-01-01

Drought negatively impacts plant growth and the productivity of crops around the world. Understanding the molecular mechanisms in the drought response is important for improvement of drought tolerance using molecular techniques. In plants, abscisic acid (ABA) is accumulated under osmotic stress conditions caused by drought, and has a key role in stress responses and tolerance. Comprehensive molecular analyses have shown that ABA regulates the expression of many genes under osmotic stress conditions, and the ABA-responsive element (ABRE) is the major cis-element for ABA-responsive gene expression. Transcription factors (TFs) are master regulators of gene expression. ABRE-binding protein and ABRE-binding factor TFs control gene expression in an ABA-dependent manner. SNF1-related protein kinases 2, group A 2C-type protein phosphatases, and ABA receptors were shown to control the ABA signaling pathway. ABA-independent signaling pathways such as dehydration-responsive element-binding protein TFs and NAC TFs are also involved in stress responses including drought, heat, and cold. Recent studies have suggested that there are interactions between the major ABA signaling pathway and other signaling factors in stress responses. The important roles of these TFs in crosstalk among abiotic stress responses will be discussed. Control of ABA or stress signaling factor expression can improve tolerance to environmental stresses. Recent studies using crops have shown that stress-specific overexpression of TFs improves drought tolerance and grain yield compared with controls in the field.

Evolving Tale of TCPs: New Paradigms and Old Lacunae

PubMed Central

Dhaka, Namrata; Bhardwaj, Vasudha; Sharma, Manoj K.; Sharma, Rita

2017-01-01

Teosinte Branched1/Cycloidea/Proliferating cell factors (TCP) genes are key mediators of genetic innovations underlying morphological novelties, stress adaptation, and evolution of immune response in plants. They have a remarkable ability to integrate and translate diverse endogenous, and environmental signals with high fidelity. Compilation of studies, aimed at elucidating the mechanism of TCP functions, shows that it takes an amalgamation and interplay of several different factors, regulatory processes and pathways, instead of individual components, to achieve the incredible functional diversity and specificity, demonstrated by TCP proteins. Through this minireview, we provide a brief description of key structural features and molecular components, known so far, that operate this conglomerate, and highlight the important conceptual challenges and lacunae in TCP research. PMID:28421104

Evolving Tale of TCPs: New Paradigms and Old Lacunae.

PubMed

Dhaka, Namrata; Bhardwaj, Vasudha; Sharma, Manoj K; Sharma, Rita

2017-01-01

Teosinte Branched1/Cycloidea/Proliferating cell factors (TCP) genes are key mediators of genetic innovations underlying morphological novelties, stress adaptation, and evolution of immune response in plants. They have a remarkable ability to integrate and translate diverse endogenous, and environmental signals with high fidelity. Compilation of studies, aimed at elucidating the mechanism of TCP functions, shows that it takes an amalgamation and interplay of several different factors, regulatory processes and pathways, instead of individual components, to achieve the incredible functional diversity and specificity, demonstrated by TCP proteins. Through this minireview, we provide a brief description of key structural features and molecular components, known so far, that operate this conglomerate, and highlight the important conceptual challenges and lacunae in TCP research.

Catholic School Principal Job Satisfaction: Keys to Retention and Recruitment

ERIC Educational Resources Information Center

Fraser, Jennifer; Brock, Barbara L.

2006-01-01

This article presents a study on principal retention in New South Wales, Australia. Factors in job retention included economic security, role enjoyment, and the opportunity to contribute. Disincentives to the principalship included lack of support from the employing authority, inadequate pay, isolation, growing responsibilities, difficult parents,…

Chapter 7 - Mapping potential vegetation type for the LANDFIRE Prototype Project

Treesearch

Tracey S. Frescino; Matthew G. Rollins

2006-01-01

Mapped potential vegetation functioned as a key component in the Landscape Fire and Resource Management Planning Tools Prototype Project (LANDFIRE Prototype Project). Disturbance regimes, vegetation response and succession, and wildland fuel dynamics across landscapes are controlled by patterns of the environmental factors (biophysical settings) that entrain the...

Rural Extension Services. Policy Research Working Paper.

ERIC Educational Resources Information Center

Anderson, Jock R.; Feder, Gershon

This paper analyzes the considerations that lead policy makers to undertake extension investments as a key public responsibility, as well as the complex set of factors and intra-agency incentives that explain variations in performance between different extension systems. The goals of extension include transferring knowledge from researchers to…

Family Correlates of Oppositional and Conduct Disorders in Children with Attention Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Pfiffner, Linda J.; McBurnett, Keith; Rathouz, Paul J.; Judice, Samuel

2005-01-01

Comorbidities among children with ADHD are key determinants of treatment response, course, and outcome. This study sought to separate family factors (parental psychopathology and parenting practices) associated with comorbid Oppositional Defiant Disorder (ODD) from those associated with Conduct Disorder (CD) among children with Attention…

Public health works: blood donation in urban China.

PubMed

Adams, Vincanne; Erwin, Kathleen; Le, Phuoc V

2009-02-01

Recent shifts in the global health infrastructure warrant consideration of the value and effectiveness of national public health campaigns. These shifts include the globalization of pharmaceutical research, the rise of NGO-funded health interventions, and the rise of biosecurity models of international health. We argue that although these trends have arisen as worthwhile responses to actual health needs, it is important to remember the key role that public health campaigns can play in the promotion of national health, especially in developing nations. Focusing on an example set by China in response to a public health crisis surrounding the national need for a clean and adequate blood supply and the inadvertent spread of HIV by way of blood donation in the early 1990's, we argue that there is an important role for strong national public health programs. We also identify the key factors that enabled China's response to this burgeoning epidemic to be, in the end, largely successful.

An integrated approach to characterize transcription factor and microRNA regulatory networks involved in Schwann cell response to peripheral nerve injury

PubMed Central

2013-01-01

Background The regenerative response of Schwann cells after peripheral nerve injury is a critical process directly related to the pathophysiology of a number of neurodegenerative diseases. This SC injury response is dependent on an intricate gene regulatory program coordinated by a number of transcription factors and microRNAs, but the interactions among them remain largely unknown. Uncovering the transcriptional and post-transcriptional regulatory networks governing the Schwann cell injury response is a key step towards a better understanding of Schwann cell biology and may help develop novel therapies for related diseases. Performing such comprehensive network analysis requires systematic bioinformatics methods to integrate multiple genomic datasets. Results In this study we present a computational pipeline to infer transcription factor and microRNA regulatory networks. Our approach combined mRNA and microRNA expression profiling data, ChIP-Seq data of transcription factors, and computational transcription factor and microRNA target prediction. Using mRNA and microRNA expression data collected in a Schwann cell injury model, we constructed a regulatory network and studied regulatory pathways involved in Schwann cell response to injury. Furthermore, we analyzed network motifs and obtained insights on cooperative regulation of transcription factors and microRNAs in Schwann cell injury recovery. Conclusions This work demonstrates a systematic method for gene regulatory network inference that may be used to gain new information on gene regulation by transcription factors and microRNAs. PMID:23387820

3-Dimesional Structure of Factor D

NASA Technical Reports Server (NTRS)

2004-01-01

The trauma caused by the open heart surgery often triggers massive inflammation because the immune system overreacts. Factor D, the protein which plays a key role in the biological steps that activate this immune response prevents the imune system from inappropriately rurning out of control, allowing the patient to recover more rapidly. Factor D blockers, with their great potential to alleviate the complication of inflammation associated with heart surgery, are now being developed for clinical trials. These new drugs, developed from space research, should be commercially available as soon as year 2001.

Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

PubMed

Koizume, Shiro; Miyagi, Yohei

2015-01-01

Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

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.

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 HIV/AIDS.

Macrophages Exhibit a Large Repertoire of Activation States via Multiple Mechanisms of Macrophage-activating Factors.

PubMed

Sumiya, Y U; Inoue, Takahiro; Ishikawa, Mami; Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Uto, Yoshihiro; Nishikata, Takahito

2016-07-01

Macrophages are important components of human defense systems and consequently key to antitumor immunity. Human-serum macrophage activation factor (serum MAF) can activate macrophages, making it a promising reagent for anticancer therapy. We established four different macrophage subtypes through introduction of different culture conditions to THP-1- and U937-derived macrophages. We assessed phagocytic activity to understand subtype responses to typical macrophage activation factors (MAFs) and the activation mechanisms of serum MAF. All four macrophage subtypes differed in their response to all MAFs. Moreover, serum MAF had two different activation mechanisms: N-acetylgalactosamine (GalNAc)-dependent and GalNAc-independent. Macrophage activation states and mechanisms are heterogeneous. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

HSP70 and heat shock factor 1 cooperate to repress Ras-induced transcriptional activation of the c-fos gene.

PubMed

He, H; Chen, C; Xie, Y; Asea, A; Calderwood, S K

2000-11-01

Heat shock protein 70 (HSP70) is a molecular chaperone involved in protein folding and resistance to the deleterious effects of stress. Here we show that HSP70 suppresses transcription of c-fos, an early response gene that is a key component of the ubiquitous AP-1 transcription factor complex. HSP70 repressed Ras-induced c-fos transcription only in the presence of functional heat shock factor1 (HSF1). This suggests that HSP70 functions as a corepressor with HSF1 to inhibit c-fos gene transcription. Therefore, besides its known function in the stress response, HSP70 also has the property of a corepressor and combines with HSF1 to antagonize Fos expression and may thus impact multiple aspects of cell regulation.

Iron and oxygen sensing: a tale of 2 interacting elements?

PubMed

Simpson, Robert J; McKie, Andrew T

2015-02-01

Iron and oxygen metabolism are intimately linked with one another. A change in the level of either metabolite results in activation of common pathways. At the heart of these responses lies a group of iron and oxygen dependent enzymes called prolyl hydroxylases. Prolyl hydroxylases (PHDs) require both iron and oxygen for optimal activity and their biological activity is to carry out the critical post-translational modification of the addition of a hydroxyl group to specific proline residues within Hypoxia Inducible Factor (HIFs)-well known transcription factors originally thought to regulate responses to hypoxia but which are now known to regulate key iron metabolism proteins too. The addition of the hydroxyl group ultimately leads to the unbiquitylation and destruction of HIFs, thus PHDs control appropriate HIF transcriptional responses depending on cellular oxygen or iron levels. There are two major HIFs; HIF1α and HIF2α. In terms of responses to iron HIF2α is of major importance in key tissues such as the intestine where several iron transporters (Ferroportin, Dcytb) contain HREs within their promoters which bind HIF2α. Furthermore the recent discovery that HIF2α contains a 5' iron responsive element (IRE) has underlined the importance of HIF2α as a major player in iron metabolism. This review brings together recent findings with regard to the HIF2α/IRP network as well as other aspects of iron sensing in cells and tissues.

Factors influencing mine rescue team behaviors.

PubMed

Jansky, Jacqueline H; Kowalski-Trakofler, K M; Brnich, M J; Vaught, C

2016-01-01

A focus group study of the first moments in an underground mine emergency response was conducted by the National Institute for Occupational Safety and Health (NIOSH), Office for Mine Safety and Health Research. Participants in the study included mine rescue team members, team trainers, mine officials, state mining personnel, and individual mine managers. A subset of the data consists of responses from participants with mine rescue backgrounds. These responses were noticeably different from those given by on-site emergency personnel who were at the mine and involved with decisions made during the first moments of an event. As a result, mine rescue team behavior data were separated in the analysis and are reported in this article. By considering the responses from mine rescue team members and trainers, it was possible to sort the data and identify seven key areas of importance to them. On the basis of the responses from the focus group participants with a mine rescue background, the authors concluded that accurate and complete information and a unity of purpose among all command center personnel are two of the key conditions needed for an effective mine rescue operation.

The thinking doctor: clinical decision making in contemporary medicine.

PubMed

Trimble, Michael; Hamilton, Paul

2016-08-01

Diagnostic errors are responsible for a significant number of adverse events. Logical reasoning and good decision-making skills are key factors in reducing such errors, but little emphasis has traditionally been placed on how these thought processes occur, and how errors could be minimised. In this article, we explore key cognitive ideas that underpin clinical decision making and suggest that by employing some simple strategies, physicians might be better able to understand how they make decisions and how the process might be optimised. © 2016 Royal College of Physicians.

Workforce perceptions of hospital safety culture: development and validation of the patient safety climate in healthcare organizations survey.

PubMed

Singer, Sara; Meterko, Mark; Baker, Laurence; Gaba, David; Falwell, Alyson; Rosen, Amy

2007-10-01

To describe the development of an instrument for assessing workforce perceptions of hospital safety culture and to assess its reliability and validity. Primary data collected between March 2004 and May 2005. Personnel from 105 U.S. hospitals completed a 38-item paper and pencil survey. We received 21,496 completed questionnaires, representing a 51 percent response rate. Based on review of existing safety climate surveys, we developed a list of key topics pertinent to maintaining a culture of safety in high-reliability organizations. We developed a draft questionnaire to address these topics and pilot tested it in four preliminary studies of hospital personnel. We modified the questionnaire based on experience and respondent feedback, and distributed the revised version to 42,249 hospital workers. We randomly divided respondents into derivation and validation samples. We applied exploratory factor analysis to responses in the derivation sample. We used those results to create scales in the validation sample, which we subjected to multitrait analysis (MTA). We identified nine constructs, three organizational factors, two unit factors, three individual factors, and one additional factor. Constructs demonstrated substantial convergent and discriminant validity in the MTA. Cronbach's alpha coefficients ranged from 0.50 to 0.89. It is possible to measure key salient features of hospital safety climate using a valid and reliable 38-item survey and appropriate hospital sample sizes. This instrument may be used in further studies to better understand the impact of safety climate on patient safety outcomes.

HIF Transcription Factors, Inflammation, and Immunity

PubMed Central

Palazon, Asis; Goldrath, Ananda; Nizet, Victor

2015-01-01

The hypoxic response in cells and tissues is mediated by the family of hypoxia-inducible factor (HIF) transcription factors that play an integral role in the metabolic changes that drive cellular adaptation to low oxygen availability. HIF expression and stabilization in immune cells can be triggered by hypoxia, but also by other factors associated with pathological stress: e.g., inflammation, infectious microorganisms, and cancer. HIF induces a number of aspects of host immune function, from boosting phagocyte microbicidal capacity to driving T cell differentiation and cytotoxic activity. Cellular metabolism is emerging as a key regulator of immunity, and it constitutes another layer of fine-tuned immune control by HIF that can dictate myeloid cell and lymphocyte development, fate, and function. Here we discuss how oxygen sensing in the immune microenvironment shapes immunological response and examine how HIF and the hypoxia pathway control innate and adaptive immunity. PMID:25367569

HIF transcription factors, inflammation, and immunity.

PubMed

Palazon, Asis; Goldrath, Ananda W; Nizet, Victor; Johnson, Randall S

2014-10-16

The hypoxic response in cells and tissues is mediated by the family of hypoxia-inducible factor (HIF) transcription factors; these play an integral role in the metabolic changes that drive cellular adaptation to low oxygen availability. HIF expression and stabilization in immune cells can be triggered by hypoxia, but also by other factors associated with pathological stress: e.g., inflammation, infectious microorganisms, and cancer. HIF induces a number of aspects of host immune function, from boosting phagocyte microbicidal capacity to driving T cell differentiation and cytotoxic activity. Cellular metabolism is emerging as a key regulator of immunity, and it constitutes another layer of fine-tuned immune control by HIF that can dictate myeloid cell and lymphocyte development, fate, and function. Here we discuss how oxygen sensing in the immune microenvironment shapes immunological response and examine how HIF and the hypoxia pathway control innate and adaptive immunity.

Regulation of Root Greening by Light and Auxin/Cytokinin Signaling in Arabidopsis[W

PubMed Central

Kobayashi, Koichi; Baba, Shinsuke; Obayashi, Takeshi; Sato, Mayuko; Toyooka, Kiminori; Keränen, Mika; Aro, Eva-Mari; Fukaki, Hidehiro; Ohta, Hiroyuki; Sugimoto, Keiko; Masuda, Tatsuru

2012-01-01

Tight coordination between plastid differentiation and plant development is best evidenced by the synchronized development of photosynthetic tissues and the biogenesis of chloroplasts. Here, we show that Arabidopsis thaliana roots demonstrate accelerated chlorophyll accumulation and chloroplast development when they are detached from shoots. However, this phenomenon is repressed by auxin treatment. Mutant analyses suggest that auxin transported from the shoot represses root greening via the function of INDOLE-3-ACETIC ACID14, AUXIN RESPONSE FACTOR7 (ARF7), and ARF19. Cytokinin signaling, on the contrary, is required for chlorophyll biosynthesis in roots. The regulation by auxin/cytokinin is dependent on the transcription factor LONG HYPOCOTYL5 (HY5), which is required for the expression of key chlorophyll biosynthesis genes in roots. The expression of yet another root greening transcription factor, GOLDEN2-LIKE2 (GLK2), was found to be regulated in opposing directions by auxin and cytokinin. Furthermore, both the hormone signaling and the GLK transcription factors modified the accumulation of HY5 in roots. Overexpression of GLKs in the hy5 mutant provided evidence that GLKs require HY5 to maximize their activities in root greening. We conclude that the combination of HY5 and GLKs, functioning downstream of light and auxin/cytokinin signaling pathways, is responsible for coordinated expression of the key genes in chloroplast biogenesis. PMID:22415275

Influenza vaccine response profiles are affected by vaccine preparation and preexisting immunity, but not HIV infection.

PubMed

Berger, Christoph T; Greiff, Victor; Mehling, Matthias; Fritz, Stefanie; Meier, Marc A; Hoenger, Gideon; Conen, Anna; Recher, Mike; Battegay, Manuel; Reddy, Sai T; Hess, Christoph

2015-01-01

Vaccines dramatically reduce infection-related morbidity and mortality. Determining factors that modulate the host response is key to rational vaccine design and demands unsupervised analysis. To longitudinally resolve influenza-specific humoral immune response dynamics we constructed vaccine response profiles of influenza A- and B-specific IgM and IgG levels from 42 healthy and 31 HIV infected influenza-vaccinated individuals. Pre-vaccination antibody levels and levels at 3 predefined time points after vaccination were included in each profile. We performed hierarchical clustering on these profiles to study the extent to which HIV infection associated immune dysfunction, adaptive immune factors (pre-existing influenza-specific antibodies, T cell responses), an innate immune factor (Mannose Binding Lectin, MBL), demographic characteristics (gender, age), or the vaccine preparation (split vs. virosomal) impacted the immune response to influenza vaccination. Hierarchical clustering associated vaccine preparation and pre-existing IgG levels with the profiles of healthy individuals. In contrast to previous in vitro and animal data, MBL levels had no impact on the adaptive vaccine response. Importantly, while HIV infected subjects with low CD4 T cell counts showed a reduced magnitude of their vaccine response, their response profiles were indistinguishable from those of healthy controls, suggesting quantitative but not qualitative deficits. Unsupervised profile-based analysis ranks factors impacting the vaccine-response by relative importance, with substantial implications for comparing, designing and improving vaccine preparations and strategies. Profile similarity between HIV infected and HIV negative individuals suggests merely quantitative differences in the vaccine response in these individuals, offering a rationale for boosting strategies in the HIV infected population.

OsDREB2A, a Rice Transcription Factor, Significantly Affects Salt Tolerance in Transgenic Soybean

PubMed Central

Ma, Qi-bin; Yang, Cun-yi; Mu, Ying-hui; Suo, Hai-cui; Luo, Lai-hui; Nian, Hai

2013-01-01

The dehydration responsive element binding (DREB) transcription factors play an important role in regulating stress-related genes. OsDREB2A, a member of the DREBP subfamily of AP2/ERF transcription factors in rice (Oryza sativa), is involved in the abiotic stress response. OsDREB2A expression is induced by drought, low-temperature and salt stresses. Here, we report the ability of OsDREB2A to regulate high-salt response in transgenic soybean. Overexpressing OsDREB2A in soybeans enhanced salt tolerance by accumulating osmolytes, such as soluble sugars and free proline, and improving the expression levels of some stress-responsive transcription factors and key genes. The phenotypic characterization of transgenic soybean were significantly better than those of wild-type (WT). Electrophoresis mobility shift assay (EMSA) revealed that the OsDREB2A can bind to the DRE core element in vitro. These results indicate that OsDREB2A may participate in abiotic stress by directly binding with DRE element to regulate the expression of downstream genes. Overexpression of OsDREB2A in soybean might be used to improve tolerance to salt stress. PMID:24376625

Alternative pathway regulation by factor H modulates Streptococcus pneumoniae induced proinflammatory cytokine responses by decreasing C5a receptor crosstalk.

PubMed

van der Maten, Erika; de Bont, Cynthia M; de Groot, Ronald; de Jonge, Marien I; Langereis, Jeroen D; van der Flier, Michiel

2016-12-01

Bacterial pathogens not only stimulate innate immune receptors, but also activate the complement system. Crosstalk between complement C5a receptor (C5aR) and other innate immune receptors is known to enhance the proinflammatory cytokine response. An important determinant of the magnitude of complement activation is the activity of the alternative pathway, which serves as an amplification mechanism for complement activation. Both alternative pathway activity as well as plasma levels of factor H, a key inhibitor of the alternative pathway, show large variation within the human population. Here, we studied the effect of factor H-mediated regulation of the alternative pathway on bacterial-induced proinflammatory cytokine responses. We used the human pathogen Streptococcus pneumoniae as a model stimulus to induce proinflammatory cytokine responses in human peripheral blood mononuclear cells. Serum containing active complement enhanced pneumococcal induced proinflammatory cytokine production through C5a release and C5aR crosstalk. We found that inhibition of the alternative pathway by factor H, with a concentration equivalent to a high physiological level, strongly reduced C5a levels and decreased proinflammatory cytokine production in human peripheral blood mononuclear cells. This suggests that variation in alternative pathway activity due to variation in factor H plasma levels affects individual cytokine responses during infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Responses of soil physical and chemical properties to karst rocky desertification evolution in typical karst valley area

NASA Astrophysics Data System (ADS)

Chen, Fei; Zhou, Dequan; Bai, Xiaoyong; zeng, Cheng; Xiao, Jianyong; Qian, Qinghuan; Luo, Guangjie

2018-01-01

In order to reveal the differences of soil physical and chemical properties and their response mechanism to the evolution of KRD. The characteristics of soil physical and chemical properties of different grades of KRD were studied by field sampling method to research different types of KRD in the typical karst valley of southern China. Instead of using space of time, to explore the response and the mechanisms of the soil physical and chemical properties at the different evolution process. The results showed that: (1) There were significant differences in organic matter, pH, total nitrogen, total phosphorus, total potassium, sediment concentration, clay content and AWHC in different levels of KRD environment. However, these indicators are not with increasing desertification degree has been degraded, but improved after a first degradation trends; (2) The correlation analysis showed that soil organic matter, acid, alkali, total nitrogen, total phosphorus, total potassium and clay contents were significantly correlated with other physical and chemical factors. They are the key factors of soil physical and chemical properties, play a key role in improving soil physical and chemical properties and promoting nutrient cycling; (3) The principal component analysis showed that the cumulative contribution rate of organic matter, pH, total nitrogen, total phosphorus, total potassium and sediment concentration was 80.26%, which was the key index to evaluate rocky desertification degree based on soil physical and chemical properties. The results have important theoretical and practical significance for the protection and restoration of rocky desertification ecosystem in southwest China.

A Comprehensive Transcriptomic and Proteomic Analysis of Hydra Head Regeneration.

PubMed

Petersen, Hendrik O; Höger, Stefanie K; Looso, Mario; Lengfeld, Tobias; Kuhn, Anne; Warnken, Uwe; Nishimiya-Fujisawa, Chiemi; Schnölzer, Martina; Krüger, Marcus; Özbek, Suat; Simakov, Oleg; Holstein, Thomas W

2015-08-01

The cnidarian freshwater polyp Hydra sp. exhibits an unparalleled regeneration capacity in the animal kingdom. Using an integrative transcriptomic and stable isotope labeling by amino acids in cell culture proteomic/phosphoproteomic approach, we studied stem cell-based regeneration in Hydra polyps. As major contributors to head regeneration, we identified diverse signaling pathways adopted for the regeneration response as well as enriched novel genes. Our global analysis reveals two distinct molecular cascades: an early injury response and a subsequent, signaling driven patterning of the regenerating tissue. A key factor of the initial injury response is a general stabilization of proteins and a net upregulation of transcripts, which is followed by a subsequent activation cascade of signaling molecules including Wnts and transforming growth factor (TGF) beta-related factors. We observed moderate overlap between the factors contributing to proteomic and transcriptomic responses suggesting a decoupled regulation between the transcriptional and translational levels. Our data also indicate that interstitial stem cells and their derivatives (e.g., neurons) have no major role in Hydra head regeneration. Remarkably, we found an enrichment of evolutionarily more recent genes in the early regeneration response, whereas conserved genes are more enriched in the late phase. In addition, genes specific to the early injury response were enriched in transposon insertions. Genetic dynamicity and taxon-specific factors might therefore play a hitherto underestimated role in Hydra regeneration. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Uncovering the Role of RNA-Binding Proteins in Gene Expression in the Immune System.

PubMed

Díaz-Muñoz, Manuel D; Turner, Martin

2018-01-01

Fighting external pathogens requires an ever-changing immune system that relies on tight regulation of gene expression. Transcriptional control is the first step to build efficient responses while preventing immunodeficiencies and autoimmunity. Post-transcriptional regulation of RNA editing, location, stability, and translation are the other key steps for final gene expression, and they are all controlled by RNA-binding proteins (RBPs). Nowadays we have a deep understanding of how transcription factors control the immune system but recent evidences suggest that post-transcriptional regulation by RBPs is equally important for both development and activation of immune responses. Here, we review current knowledge about how post-transcriptional control by RBPs shapes our immune system and discuss the perspective of RBPs being the key players of a hidden immune cell epitranscriptome.

In Vitro Studies on the Antimicrobial Peptide Human Beta-Defensin 9 (HBD9): Signalling Pathways and Pathogen-Related Response (An American Ophthalmological Society Thesis)

PubMed Central

Dua, Harminder S.; Otri, Ahmad Muneer; Hopkinson, Andrew; Mohammed, Imran

2014-01-01

Purpose: Human β-defensins (HBDs) are an important part of the innate immune host defense at the ocular surface. Unlike other defensins, expression of HBD9 at the ocular surface is reduced during microbial infection, but activation of toll-like receptor 2 (TLR2) in corneal epithelial cells has been shown to up-regulate HBD9. Our purpose was to test the hypothesis that TLR2 has a key role in the signalling pathway(s) involved in the overexpression or underexpression of HBD9, and accordingly, different pathogens would induce a different expression pattern of HBD9. Methods: The in vitro RNAi silencing method and response to dexamethasone were used to determine key molecules involved in signalling pathways of HBD9 in immortalized human corneal epithelial cells. The techniques included cell culture with exposure to specific transcription factor inhibitors and bacteria, RNA extraction and cDNA synthesis, quantitative real-time polymerase chain reaction, and immunohistology. Results: This study demonstrates that TLR2 induces HBD9 mRNA and protein expression in a time- and dose-dependent manner. Transforming growth factor-β–activated kinase 1 (TAK1) plays a central role in HBD9 induction by TLR2, and transcription factors c-JUN and activating transcription factor 2 are also involved. Dexamethasone reduces TLR2-mediated up-regulation of HBD9 mRNA and protein levels in mitogen-activated protein kinase phosphatase 1 (MKP1)-dependent and c-JUN-independent manner. HBD9 expression differs with gram-negative and gram-positive bacteria. Conclusions: TLR2-mediated MKPs and nuclear factor-κB signalling pathways are involved in HBD9 expression. TAK-1 is a key molecule. These molecules can be potentially targeted to modulate HBD9 expression. Differential expression of HBD9 with different bacteria could be related to differences in pathogen-associated molecular patterns of these organisms. PMID:25646028

Toward Understanding Trust: A Response to Adams and Miskell

ERIC Educational Resources Information Center

Romero, Lisa S.; Mitchell, Douglas E.

2018-01-01

Purpose: Trust is a key component of successful schools. Although scholars widely agree that trust is multifaceted, there is less agreement about the number and nature of these factors. In the October 2016 issue of "Educational Administration Quarterly," C. M. Adams and Miskell (see EJ1112413) argued that their Teacher Trust of District…

Culturally Responsive Mathematics Pedagogy: A Bridge Too Far?

ERIC Educational Resources Information Center

Sparrow, Len; Hurst, Chris

2012-01-01

The Swan Valley Cluster of Schools for the Make it Count project identified the professional learning of teachers as a key factor in improving the numeracy outcomes of urban Indigenous children. Two mentor teachers were assigned to support cluster teachers in planning and teaching mathematics during 2011. This paper reports on the initiative and…

A Comparison Between Genotyping-by-sequencing and Array-based Scoring of SNPs for Genomic Prediction Accuracy in Winter Wheat

USDA-ARS?s Scientific Manuscript database

The utilization of DNA molecular markers in plant breeding to maximize selection response via marker assisted selection (MAS) and genomic selection (GS) has the potential to revolutionize plant breeding. A key factor affecting GS applicability is the choice of molecular marker platform. Genotypying-...

Transforming Facilities to Achieve Student Success. APPA Thought Leaders Series 2017

ERIC Educational Resources Information Center

APPA: Association of Higher Education Facilities Officers, 2017

2017-01-01

The 2017 Thought Leaders report focuses on "Transforming Facilities to Achieve Student Success." The report makes the case that student success starts with retention and graduation, but it can expand to include factors from personal career goals to social responsibility. A key message from the report is that through strategic investment…

Entrepreneurial Thinking and Action--An Educational Responsibility for Europe

ERIC Educational Resources Information Center

Eickhoff, Markus Th.

2008-01-01

In a general sense, entrepreneurial thinking and action relates to all those in employment, as an attitude to work and working behaviour, and it is accordingly becoming a key factor in competence. For independent entrepreneurs it is also, in a more specific sense, a fundamental precondition for successfully establishing and operating an…

Personnel Preparation in Visual Impairment: A Responsive, Individualized Model

ERIC Educational Resources Information Center

Bozeman, Laura A.; Brusegaard, Callie M.; McCulley, Robert M.

2018-01-01

A key factor in promoting the outcomes described in the mission statement of the National Plan for Training Personnel (NPTP) to Serve Children with Blindness and Low Vision is the teacher. Specifically, knowledge of subject matter tied to national standards along with effective pedagogy can positively influence student learning. For aspiring…

The Perception of Error in Production Plants of a Chemical Organisation

ERIC Educational Resources Information Center

Seifried, Jurgen; Hopfer, Eva

2013-01-01

There is considerable current interest in error-friendly corporate culture, one particular research question being how and under what conditions errors are learnt from in the workplace. This paper starts from the assumption that errors are inevitable and considers key factors which affect learning from errors in high responsibility organisations,…

Ecological genetics of floret mass variation in Bromus tectorum (Poaceae)

Treesearch

Susan E. Meyer

2010-01-01

Bromus tectorum L. (cheatgrass, downy brome) is a highly invasive inbreeding annual grass that dominates millions of hectares of former shrubland in interior western North America. Factors contributing to its success include strong genetic regulation of key adaptive traits coupled with high phenotypic plasticity in response to resource availability (Meyer and Allen...

Comparative bioinformatics analysis of transcription factor genes indicates conservation of key regulatory domains among babesia bovis, babesia microti and theileria equi.

USDA-ARS?s Scientific Manuscript database

Apicomplexa tick borne hemoparasites including B. bovis, B. microti, and Theileria equi are responsible for bovine and human babesiosis and equine theileriosis respectively. These neglected parasites of vast medical, epidemiological, and economic impact have complex life cycles in their vertebrate a...

Young Children's Analogical Reasoning across Cultures: Similarities and Differences

ERIC Educational Resources Information Center

Richland, Lindsey Engle; Chan, Tsz-Kit; Morrison, Robert G.; Au, Terry Kit-Fong

2010-01-01

A cross-cultural comparison between U.S. and Hong Kong preschoolers examined factors responsible for young children's analogical reasoning errors. On a scene analogy task, both groups had adequate prerequisite knowledge of the key relations, were the same age, and showed similar baseline performance, yet Chinese children outperformed U.S. children…

Identifying a key physical factor sensitive to the performance of Madden-Julian oscillation simulation in climate models

NASA Astrophysics Data System (ADS)

Kim, Go-Un; Seo, Kyong-Hwan

2018-01-01

A key physical factor in regulating the performance of Madden-Julian oscillation (MJO) simulation is examined by using 26 climate model simulations from the World Meteorological Organization's Working Group for Numerical Experimentation/Global Energy and Water Cycle Experiment Atmospheric System Study (WGNE and MJO-Task Force/GASS) global model comparison project. For this, intraseasonal moisture budget equation is analyzed and a simple, efficient physical quantity is developed. The result shows that MJO skill is most sensitive to vertically integrated intraseasonal zonal wind convergence (ZC). In particular, a specific threshold value of the strength of the ZC can be used as distinguishing between good and poor models. An additional finding is that good models exhibit the correct simultaneous convection and large-scale circulation phase relationship. In poor models, however, the peak circulation response appears 3 days after peak rainfall, suggesting unfavorable coupling between convection and circulation. For an improving simulation of the MJO in climate models, we propose that this delay of circulation in response to convection needs to be corrected in the cumulus parameterization scheme.

The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy.

PubMed

Gopalakrishnan, Vancheswaran; Helmink, Beth A; Spencer, Christine N; Reuben, Alexandre; Wargo, Jennifer A

2018-04-09

The microbiome is receiving significant attention given its influence on a host of human diseases including cancer. Its role in response to cancer treatment is becoming increasingly apparent, with evidence suggesting that modulating the gut microbiome may affect responses to numerous forms of cancer therapy. A working knowledge of the microbiome is vital as we move forward in this age of precision medicine, and an understanding of the microbiome's influence on immune responses and cancer is key. It is also important to understand factors influencing the gut microbiome and strategies to manipulate the microbiome to augment therapeutic responses. Copyright © 2018 Elsevier Inc. All rights reserved.

Exercise Dose in Clinical Practice

PubMed Central

Wasfy, Meagan; Baggish, Aaron L.

2016-01-01

There is wide variability in the physical activity patterns of the patients in contemporary clinical cardiovascular practice. This review is designed to address the impact of exercise dose on key cardiovascular risk factors and on mortality. We begin by examining the body of literature that supports a dose-response relationship between exercise and cardiovascular disease risk factors including plasma lipids, hypertension, diabetes mellitus, and obesity. We next explore the relationship between exercise dose and mortality by reviewing the relevant epidemiological literature underlying current physical activity guideline recommendations. We then expand this discussion to critically examine recent data pertaining to the impact of exercise dose at the lowest and highest ends of the spectrum. Finally, we provide a framework for how the key concepts of exercise dose can be integrated into clinical practice. PMID:27267537

Exercise Dose in Clinical Practice.

PubMed

Wasfy, Meagan M; Baggish, Aaron L

2016-06-07

There is wide variability in the physical activity patterns of the patients in contemporary clinical cardiovascular practice. This review is designed to address the impact of exercise dose on key cardiovascular risk factors and on mortality. We begin by examining the body of literature that supports a dose-response relationship between exercise and cardiovascular disease risk factors, including plasma lipids, hypertension, diabetes mellitus, and obesity. We next explore the relationship between exercise dose and mortality by reviewing the relevant epidemiological literature underlying current physical activity guideline recommendations. We then expand this discussion to critically examine recent data pertaining to the impact of exercise dose at the lowest and highest ends of the spectrum. Finally, we provide a framework for how the key concepts of exercise dose can be integrated into clinical practice. © 2016 American Heart Association, Inc.

Multi-Agent Simulations of the Immune Response to Hiv during the Acute Stage of Infection

NASA Astrophysics Data System (ADS)

Walshe, R.; Ruskin, H. J.; Callaghan, A.

Results of multi-agent based simulations of the immune response to HIV during the acute phase of infection are presented here. The model successfully recreates the viral dynamics associated with the acute phase of infection, i.e., a rapid rise in viral load followed by a sharp decline to what is often referred to as a "set point", a result of T-cell response and emergence of HIV neutralizing antibodies. The results indicate that sufficient T Killer cell response is the key factor in controlling viral growth during this phase with antibody levels of critical importance only in the absence of a sufficient T Killer response.

The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways.

PubMed

Derous, Davina; Mitchell, Sharon E; Green, Cara L; Chen, Luonan; Han, Jing-Dong J; Wang, Yingchun; Promislow, Daniel E L; Lusseau, David; Speakman, John R; Douglas, Alex

2016-04-01

Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti-ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin-like growth factor 1 (IGF-1), insulin, and tumor necrosis factor alpha (TNF-α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF-α, leptin and IGF-1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes.

The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways

PubMed Central

Green, Cara L.; Chen, Luonan; Han, Jing‐Dong J.; Wang, Yingchun; Promislow, Daniel E.L.; Lusseau, David; Speakman, John R.; Douglas, Alex

2016-01-01

Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti‐ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin‐like growth factor 1 (IGF‐1), insulin, and tumor necrosis factor alpha (TNF‐α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF‐α, leptin and IGF‐1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes. PMID:26945906

NRF2-regulation in brain health and disease: implication of cerebral inflammation

PubMed Central

Sandberg, Mats; Patil, Jaspal; D’Angelo, Barbara; Weber, Stephen G; Mallard, Carina

2014-01-01

The nuclear factor erythroid 2 related factor 2 (NRF2) is a key regulator of endogenous inducible defense systems in the body. Under physiological conditions NRF2 is mainly located in the cytoplasm. However, in response to oxidative stress, NRF2 translocates to the nucleus and binds to specific DNA sites termed “anti-oxidant response elements” or “electrophile response elements” to initiate transcription of cytoprotective genes. Acute oxidative stress to the brain, such as stroke and traumatic brain injury is increased in animals that are deficient in NRF2. Insufficient NRF2 activation in humans has been linked to chronic diseases such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis. New findings have also linked activation of the NRF2 system to anti-inflammatory effects via interactions with NF-κB. Here we review literature on cellular mechanisms of NRF2 regulation, how to maintain and restore NRF2 function and the relationship between NRF2 regulation and brain damage. We bring forward the hypothesis that inflammation via prolonged activation of key kinases (p38 and GSK-3β) and activation of histone deacetylases gives rise to dysregulation of the NRF2 system in the brain, which contributes to oxidative stress and injury. PMID:24262633

Plant Nucleolar Stress Response, a New Face in the NAC-Dependent Cellular Stress Responses.

PubMed

Ohbayashi, Iwai; Sugiyama, Munetaka

2017-01-01

The nucleolus is the most prominent nuclear domain, where the core processes of ribosome biogenesis occur vigorously. All these processes are finely orchestrated by many nucleolar factors to build precisely ribosome particles. In animal cells, perturbations of ribosome biogenesis, mostly accompanied by structural disorders of the nucleolus, cause a kind of cellular stress to induce cell cycle arrest, senescence, or apoptosis, which is called nucleolar stress response. The best-characterized pathway of this stress response involves p53 and MDM2 as key players. p53 is a crucial transcription factor that functions in response to not only nucleolar stress but also other cellular stresses such as DNA damage stress. These cellular stresses release p53 from the inhibition by MDM2, an E3 ubiquitin ligase targeting p53, in various ways, which leads to p53-dependent activation of a set of genes. In plants, genetic impairments of ribosome biogenesis factors or ribosome components have been shown to cause characteristic phenotypes, including a narrow and pointed leaf shape, implying a common signaling pathway connecting ribosomal perturbations and certain aspects of growth and development. Unlike animals, however, plants have neither p53 nor MDM2 family proteins. Then the question arises whether plant cells have a nucleolar stress response pathway. In recent years, it has been reported that several members of the plant-specific transcription factor family NAC play critical roles in the pathways responsive to various cellular stresses. In this mini review, we outline the plant cellular stress response pathways involving NAC transcription factors with reference to the p53-MDM2-dependent pathways of animal cells, and discuss the possible involvement of a plant-unique, NAC-mediated pathway in the nucleolar stress response in plants.

River Sensitivity and Catchment Connectivity: Key Controls on Geomorphic Response and Effectiveness

NASA Astrophysics Data System (ADS)

Lisenby, P.; Fryirs, K.; Croke, J.

2016-12-01

The sensitivity of river channels to adjustment and the dynamics of sediment connectivity along a channel network are key controls on the capacity (ability) for a river system to adjust, i.e. the severity, distribution, and type of geomorphic response to disturbance events. In turn, the cumulative impact of geomorphic responses compared with event magnitude will determine the geomorphic effectiveness of a single disturbance event. River sensitivity and sediment connectivity can change significantly over space and time, and vary with changes in internal factors such as channel type and geomorphic landform and external factors such as event sequencing and lithological controls. Correspondingly, the capacity for a geomorphic system to respond to disturbance events will also vary, so that geomorphic effectiveness is not definitively characterized by a static relationship between event magnitude and geomorphic response, but rather is a dynamic comparison between geomorphic response and an actively changing capacity for geomorphic adjustment. Herein, we use the Lockyer Valley, Queensland as a case study to illustrate the variability of river sensitivity and sediment connectivity. We relate this variability to the potential and capacity for geomorphic channel response. We find that the sensitivity to and capacity for geomorphic adjustment varies significantly with channel morphometry and valley position. Additionally, the nature of bedload sediment connectivity changes with the distribution of geomorphic landforms and channel weirs that can impede sediment transference through the system. This variability of river sensitivity and sediment connectivity will control the nature of geomorphic response to disturbance events within the Lockyer Valley. Ultimately, determinations of geomorphic effectiveness for disturbance events will depend on comparisons of their geomorphic impacts with the capacity of the Lockyer geomorphic system to respond.

Translational models of tumor angiogenesis: A nexus of in silico and in vitro models.

PubMed

Soleimani, Shirin; Shamsi, Milad; Ghazani, Mehran Akbarpour; Modarres, Hassan Pezeshgi; Valente, Karolina Papera; Saghafian, Mohsen; Ashani, Mehdi Mohammadi; Akbari, Mohsen; Sanati-Nezhad, Amir

2018-03-05

Emerging evidence shows that endothelial cells are not only the building blocks of vascular networks that enable oxygen and nutrient delivery throughout a tissue but also serve as a rich resource of angiocrine factors. Endothelial cells play key roles in determining cancer progression and response to anti-cancer drugs. Furthermore, the endothelium-specific deposition of extracellular matrix is a key modulator of the availability of angiocrine factors to both stromal and cancer cells. Considering tumor vascular network as a decisive factor in cancer pathogenesis and treatment response, these networks need to be an inseparable component of cancer models. Both computational and in vitro experimental models have been extensively developed to model tumor-endothelium interactions. While informative, they have been developed in different communities and do not yet represent a comprehensive platform. In this review, we overview the necessity of incorporating vascular networks for both in vitro and in silico cancer models and discuss recent progresses and challenges of in vitro experimental microfluidic cancer vasculature-on-chip systems and their in silico counterparts. We further highlight how these two approaches can merge together with the aim of presenting a predictive combinatorial platform for studying cancer pathogenesis and testing the efficacy of single or multi-drug therapeutics for cancer treatment. Copyright © 2018. Published by Elsevier Inc.

Possible causes of data model discrepancy in the temperature history of the last Millennium.

PubMed

Neukom, Raphael; Schurer, Andrew P; Steiger, Nathan J; Hegerl, Gabriele C

2018-05-15

Model simulations and proxy-based reconstructions are the main tools for quantifying pre-instrumental climate variations. For some metrics such as Northern Hemisphere mean temperatures, there is remarkable agreement between models and reconstructions. For other diagnostics, such as the regional response to volcanic eruptions, or hemispheric temperature differences, substantial disagreements between data and models have been reported. Here, we assess the potential sources of these discrepancies by comparing 1000-year hemispheric temperature reconstructions based on real-world paleoclimate proxies with climate-model-based pseudoproxies. These pseudoproxy experiments (PPE) indicate that noise inherent in proxy records and the unequal spatial distribution of proxy data are the key factors in explaining the data-model differences. For example, lower inter-hemispheric correlations in reconstructions can be fully accounted for by these factors in the PPE. Noise and data sampling also partly explain the reduced amplitude of the response to external forcing in reconstructions compared to models. For other metrics, such as inter-hemispheric differences, some, although reduced, discrepancy remains. Our results suggest that improving proxy data quality and spatial coverage is the key factor to increase the quality of future climate reconstructions, while the total number of proxy records and reconstruction methodology play a smaller role.

Explosive Tandem and Segmental Duplications of Multigenic Families in Eucalyptus grandis

PubMed Central

Li, Qiang; Yu, Hong; Cao, Phi Bang; Fawal, Nizar; Mathé, Catherine; Azar, Sahar; Cassan-Wang, Hua; Myburg, Alexander A.; Grima-Pettenati, Jacqueline; Marque, Christiane; Teulières, Chantal; Dunand, Christophe

2015-01-01

Plant organisms contain a large number of genes belonging to numerous multigenic families whose evolution size reflects some functional constraints. Sequences from eight multigenic families, involved in biotic and abiotic responses, have been analyzed in Eucalyptus grandis and compared with Arabidopsis thaliana. Two transcription factor families APETALA 2 (AP2)/ethylene responsive factor and GRAS, two auxin transporter families PIN-FORMED and AUX/LAX, two oxidoreductase families (ascorbate peroxidases [APx] and Class III peroxidases [CIII Prx]), and two families of protective molecules late embryogenesis abundant (LEA) and DNAj were annotated in expert and exhaustive manner. Many recent tandem duplications leading to the emergence of species-specific gene clusters and the explosion of the gene numbers have been observed for the AP2, GRAS, LEA, PIN, and CIII Prx in E. grandis, while the APx, the AUX/LAX and DNAj are conserved between species. Although no direct evidence has yet demonstrated the roles of these recent duplicated genes observed in E. grandis, this could indicate their putative implications in the morphological and physiological characteristics of E. grandis, and be the key factor for the survival of this nondormant species. Global analysis of key families would be a good criterion to evaluate the capabilities of some organisms to adapt to environmental variations. PMID:25769696

Implementing large-scale programmes to optimise the health workforce in low- and middle-income settings: a multicountry case study synthesis.

PubMed

Gopinathan, Unni; Lewin, Simon; Glenton, Claire

2014-12-01

To identify factors affecting the implementation of large-scale programmes to optimise the health workforce in low- and middle-income countries. We conducted a multicountry case study synthesis. Eligible programmes were identified through consultation with experts and using Internet searches. Programmes were selected purposively to match the inclusion criteria. Programme documents were gathered via Google Scholar and PubMed and from key informants. The SURE Framework - a comprehensive list of factors that may influence the implementation of health system interventions - was used to organise the data. Thematic analysis was used to identify the key issues that emerged from the case studies. Programmes from Brazil, Ethiopia, India, Iran, Malawi, Venezuela and Zimbabwe were selected. Key system-level factors affecting the implementation of the programmes were related to health worker training and continuing education, management and programme support structures, the organisation and delivery of services, community participation, and the sociopolitical environment. Existing weaknesses in health systems may undermine the implementation of large-scale programmes to optimise the health workforce. Changes in the roles and responsibilities of cadres may also, in turn, impact the health system throughout. © 2014 John Wiley & Sons Ltd.

The Molecular Mechanism of Ethylene-Mediated Root Hair Development Induced by Phosphate Starvation

PubMed Central

Song, Li; Yu, Haopeng; Dong, Jinsong; Liu, Dong

2016-01-01

Enhanced root hair production, which increases the root surface area for nutrient uptake, is a typical adaptive response of plants to phosphate (Pi) starvation. Although previous studies have shown that ethylene plays an important role in root hair development induced by Pi starvation, the underlying molecular mechanism is not understood. In this work, we characterized an Arabidopsis mutant, hps5, that displays constitutive ethylene responses and increased sensitivity to Pi starvation due to a mutation in the ethylene receptor ERS1. hps5 accumulates high levels of EIN3 protein, a key transcription factor involved in the ethylene signaling pathway, under both Pi sufficiency and deficiency. Pi starvation also increases the accumulation of EIN3 protein. Combined molecular, genetic, and genomic analyses identified a group of genes that affect root hair development by regulating cell wall modifications. The expression of these genes is induced by Pi starvation and is enhanced in the EIN3-overexpressing line. In contrast, the induction of these genes by Pi starvation is suppressed in ein3 and ein3eil1 mutants. EIN3 protein can directly bind to the promoter of these genes, some of which are also the immediate targets of RSL4, a key transcription factor that regulates root hair development. Based on these results, we propose that under normal growth conditions, the level of ethylene is low in root cells; a group of key transcription factors, including RSL4 and its homologs, trigger the transcription of their target genes to promote root hair development; Pi starvation increases the levels of the protein EIN3, which directly binds to the promoters of the genes targeted by RSL4 and its homologs and further increase their transcription, resulting in the enhanced production of root hairs. This model not only explains how ethylene mediates root hair responses to Pi starvation, but may provide a general mechanism for how ethylene regulates root hair development under both stress and non-stress conditions. PMID:27427911

An IRF-3-, IRF-5-, and IRF-7-Independent Pathway of Dengue Viral Resistance Utilizes IRF-1 to Stimulate Type I and II Interferon Responses.

PubMed

Carlin, Aaron F; Plummer, Emily M; Vizcarra, Edward A; Sheets, Nicholas; Joo, Yunichel; Tang, William; Day, Jeremy; Greenbaum, Jay; Glass, Christopher K; Diamond, Michael S; Shresta, Sujan

2017-11-07

Interferon-regulatory factors (IRFs) are a family of transcription factors (TFs) that translate viral recognition into antiviral responses, including type I interferon (IFN) production. Dengue virus (DENV) and other clinically important flaviviruses are suppressed by type I IFN. While mice lacking the type I IFN receptor (Ifnar1 -/- ) succumb to DENV infection, we found that mice deficient in three transcription factors controlling type I IFN production (Irf3 -/- Irf5 -/- Irf7 -/- triple knockout [TKO]) survive DENV challenge. DENV infection of TKO mice resulted in minimal type I IFN production but a robust type II IFN (IFN-γ) response. Using loss-of-function approaches for various molecules, we demonstrate that the IRF-3-, IRF-5-, IRF-7-independent pathway predominantly utilizes IFN-γ and, to a lesser degree, type I IFNs. This pathway signals via IRF-1 to stimulate interleukin-12 (IL-12) production and IFN-γ response. These results reveal a key antiviral role for IRF-1 by activating both type I and II IFN responses during DENV infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Nonlinear, interacting responses to climate limit grassland production under global change.

PubMed

Zhu, Kai; Chiariello, Nona R; Tobeck, Todd; Fukami, Tadashi; Field, Christopher B

2016-09-20

Global changes in climate, atmospheric composition, and pollutants are altering ecosystems and the goods and services they provide. Among approaches for predicting ecosystem responses, long-term observations and manipulative experiments can be powerful approaches for resolving single-factor and interactive effects of global changes on key metrics such as net primary production (NPP). Here we combine both approaches, developing multidimensional response surfaces for NPP based on the longest-running, best-replicated, most-multifactor global-change experiment at the ecosystem scale-a 17-y study of California grassland exposed to full-factorial warming, added precipitation, elevated CO2, and nitrogen deposition. Single-factor and interactive effects were not time-dependent, enabling us to analyze each year as a separate realization of the experiment and extract NPP as a continuous function of global-change factors. We found a ridge-shaped response surface in which NPP is humped (unimodal) in response to temperature and precipitation when CO2 and nitrogen are ambient, with peak NPP rising under elevated CO2 or nitrogen but also shifting to lower temperatures. Our results suggest that future climate change will push this ecosystem away from conditions that maximize NPP, but with large year-to-year variability.

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.

Pleural mesothelial cells in pleural and lung diseases

PubMed Central

Antony, Veena B.

2015-01-01

During development, the mesoderm maintains a complex relationship with the developing endoderm giving rise to the mature lung. Pleural mesothelial cells (PMCs) derived from the mesoderm play a key role during the development of the lung. The pleural mesothelium differentiates to give rise to the endothelium and smooth muscle cells via epithelial-to-mesenchymal transition (EMT). An aberrant recapitulation of such developmental pathways can play an important role in the pathogenesis of disease processes such as idiopathic pulmonary fibrosis (IPF). The PMC is the central component of the immune responses of the pleura. When exposed to noxious stimuli, it demonstrates innate immune responses such as Toll-like receptor (TLR) recognition of pathogen associated molecular patterns as well as causes the release of several cytokines to activate adaptive immune responses. Development of pleural effusions occurs due to an imbalance in the dynamic interaction between junctional proteins, n-cadherin and β-catenin, and phosphorylation of adherens junctions between PMCs, which is caused in part by vascular endothelial growth factor (VEGF) released by PMCs. PMCs play an important role in defense mechanisms against bacterial and mycobacterial pleural infections, and in pathogenesis of malignant pleural effusion, asbestos related pleural disease and malignant pleural mesothelioma. PMCs also play a key role in the resolution of inflammation, which can occur with or without fibrosis. Fibrosis occurs as a result of disordered fibrin turnover and due to the effects of cytokines such as transforming growth factor-β, platelet-derived growth factor (PDGF), and basic fibroblast growth factor; which are released by PMCs. Recent studies have demonstrated a role for PMCs in the pathogenesis of IPF suggesting their potential as a cellular biomarker of disease activity and as a possible therapeutic target. Pleural-based therapies targeting PMCs for treatment of IPF and other lung diseases need further exploration. PMID:26150910

Microgravity

NASA Image and Video Library

2004-04-15

The trauma caused by the open heart surgery often triggers massive inflammation because the immune system overreacts. Factor D, the protein which plays a key role in the biological steps that activate this immune response prevents the imune system from inappropriately rurning out of control, allowing the patient to recover more rapidly. Factor D blockers, with their great potential to alleviate the complication of inflammation associated with heart surgery, are now being developed for clinical trials. These new drugs, developed from space research, should be commercially available as soon as year 2001.

NLRC5: a key regulator of MHC class I-dependent immune responses.

PubMed

Kobayashi, Koichi S; van den Elsen, Peter J

2012-12-01

The expression of MHC class I molecules is crucial for the initiation and regulation of adaptive immune responses against pathogens. NOD-, LRR- and CARD-containing 5 (NLRC5) was recently identified as a specific transactivator of MHC class I genes (CITA). NLRC5 and the master regulator for MHC class II genes, class II transactivator (CIITA), interact with similar MHC promoter-bound factors. Here, we provide a broad overview of the molecular mechanisms behind MHC class I transcription and the role of the class I transactivator NLRC5 in MHC class I-dependent immune responses.

Hepatitis C virus and antiviral innate immunity: who wins at tug-of-war?

PubMed

Yang, Da-Rong; Zhu, Hai-Zhen

2015-04-07

Hepatitis C virus (HCV) is a major human pathogen of chronic hepatitis and related liver diseases. Innate immunity is the first line of defense against invading foreign pathogens, and its activation is dependent on the recognition of these pathogens by several key sensors. The interferon (IFN) system plays an essential role in the restriction of HCV infection via the induction of hundreds of IFN-stimulated genes (ISGs) that inhibit viral replication and spread. However, numerous factors that trigger immune dysregulation, including viral factors and host genetic factors, can help HCV to escape host immune response, facilitating viral persistence. In this review, we aim to summarize recent advances in understanding the innate immune response to HCV infection and the mechanisms of ISGs to suppress viral survival, as well as the immune evasion strategies for chronic HCV infection.

Pay attention to me! Late ERPs reveal gender differences in attention allocated to romantic partners.

PubMed

Burdwood, Erin N; Simons, Robert F

2016-04-01

The present study employed late ERPs to examine differences in the association between neural responses to romantic partners and relationship quality factors across men and women. Participants passively viewed photos of their romantic partners, celebrities, and strangers during a computerized facial processing task. All participants demonstrated enhanced positivity to partner faces at late ERP components (P3 and LPP), furthering the notion that significant others elicit more motivated and sustained attention than do other familiar or unfamiliar individuals. Neural responses to romantic partner faces were influenced by factors including overall relationship quality, investment, and communication quality, with associations varying by gender. Results highlight the key role that relationship quality factors play in the immediate processing of romantic partners-a finding with implications for couples counseling and research. © 2015 Society for Psychophysiological Research.

HSP70 and heat shock factor 1 cooperate to repress Ras-induced transcriptional activation of the c-fos gene

PubMed Central

He, Haiying; Chen, Changmin; Xie, Yue; Asea, Alexzander; Calderwood, Stuart K.

2000-01-01

Heat shock protein 70 (HSP70) is a molecular chaperone involved in protein folding and resistance to the deleterious effects of stress. Here we show that HSP70 suppresses transcription of c-fos, an early response gene that is a key component of the ubiquitous AP-1 transcription factor complex. HSP70 repressed Ras-induced c-fos transcription only in the presence of functional heat shock factor1 (HSF1). This suggests that HSP70 functions as a corepressor with HSF1 to inhibit c-fos gene transcription. Therefore, besides its known function in the stress response, HSP70 also has the property of a corepressor and combines with HSF1 to antagonize Fos expression and may thus impact multiple aspects of cell regulation. PMID:11189444

Initial Gut Microbial Composition as a Key Factor Driving Host Response to Antibiotic Treatment, as Exemplified by the Presence or Absence of Commensal Escherichia coli

PubMed Central

Ju, Tingting; Shoblak, Yasmeen; Gao, Yanhua; Yang, Kaiyuan; Fouhse, Janelle; Finlay, B. Brett; So, Yee Wing; Stothard, Paul

2017-01-01

ABSTRACT Antibiotics are important for treating bacterial infection; however, efficacies and side effects of antibiotics vary in medicine and experimental models. A few studies have correlated microbiota composition variations with health outcomes in response to antibiotics; however, no study has demonstrated causality. We had noted variation in colonic expression of C-type lectins, regenerating islet-derived protein 3β (Reg3β) and Reg3γ, after metronidazole treatment in a mouse model. To investigate the effects of specific variations in the preexisting microbiome on host response to antibiotics, mice harboring a normal microbiota were allocated to 4 treatments in a 2-by-2 factorial arrangement with or without commensal Escherichia coli and with or without metronidazole in drinking water. E. coli colonized readily without causing a notable shift in the microbiota or host response. Metronidazole administration reduced microbiota biodiversity, indicated by decreased Chao1 and Shannon index values, and altered microbiota composition. However, the presence of E. coli strongly affected metronidazole-induced microbiota shifts. Remarkably, this single commensal bacterium in the context of a complex population led to variations in host responses to metronidazole treatment, including increased expression of antimicrobial peptides Reg3β and Reg3γ and intestinal inflammation indicated by tumor necrosis factor alpha levels. Similar results were obtained from 2-week antibiotic exposure and with additional E. coli isolates. The results of this proof-of-concept study indicate that even minor variations in initial commensal microbiota can drive shifts in microbial composition and host response after antibiotic administration. As well as providing an explanation for variability in animal models using antibiotics, the findings encourage the development of personalized medication in antibiotic therapies. IMPORTANCE This work provides an understanding of variability in studies where antibiotics are used to alter the gut microbiota to generate a host response. Furthermore, although providing evidence only for the one antibiotic, the study demonstrated that initial gut microbial composition is a key factor driving host response to antibiotic administration, creating a compelling argument for considering personalized medication based on individual variations in gut microbiota. PMID:28667114

Initial Gut Microbial Composition as a Key Factor Driving Host Response to Antibiotic Treatment, as Exemplified by the Presence or Absence of Commensal Escherichia coli.

PubMed

Ju, Tingting; Shoblak, Yasmeen; Gao, Yanhua; Yang, Kaiyuan; Fouhse, Janelle; Finlay, B Brett; So, Yee Wing; Stothard, Paul; Willing, Benjamin P

2017-09-01

Antibiotics are important for treating bacterial infection; however, efficacies and side effects of antibiotics vary in medicine and experimental models. A few studies have correlated microbiota composition variations with health outcomes in response to antibiotics; however, no study has demonstrated causality. We had noted variation in colonic expression of C-type lectins, regenerating islet-derived protein 3β (Reg3β) and Reg3γ, after metronidazole treatment in a mouse model. To investigate the effects of specific variations in the preexisting microbiome on host response to antibiotics, mice harboring a normal microbiota were allocated to 4 treatments in a 2-by-2 factorial arrangement with or without commensal Escherichia coli and with or without metronidazole in drinking water. E. coli colonized readily without causing a notable shift in the microbiota or host response. Metronidazole administration reduced microbiota biodiversity, indicated by decreased Chao1 and Shannon index values, and altered microbiota composition. However, the presence of E. coli strongly affected metronidazole-induced microbiota shifts. Remarkably, this single commensal bacterium in the context of a complex population led to variations in host responses to metronidazole treatment, including increased expression of antimicrobial peptides Reg3β and Reg3γ and intestinal inflammation indicated by tumor necrosis factor alpha levels. Similar results were obtained from 2-week antibiotic exposure and with additional E. coli isolates. The results of this proof-of-concept study indicate that even minor variations in initial commensal microbiota can drive shifts in microbial composition and host response after antibiotic administration. As well as providing an explanation for variability in animal models using antibiotics, the findings encourage the development of personalized medication in antibiotic therapies. IMPORTANCE This work provides an understanding of variability in studies where antibiotics are used to alter the gut microbiota to generate a host response. Furthermore, although providing evidence only for the one antibiotic, the study demonstrated that initial gut microbial composition is a key factor driving host response to antibiotic administration, creating a compelling argument for considering personalized medication based on individual variations in gut microbiota. Copyright © 2017 American Society for Microbiology.

Determining the key drivers and mitigating factors that influence the role of the Nurse and/or Midwife Consultant: a cross-sectional survey.

PubMed

Fernandez, Ritin S; Sheppard-Law, Suzanne; Manning, Vicki

2017-06-01

Globally, many nurses and midwives are working at an advanced practice level. The role of a Nurse and/or Midwife Consultant encompasses a diverse and complex interaction between five specified domains namely Clinical Service and Consultancy, Clinical Leadership, Research, Education, and Clinical Services Planning and Management. The objective of this replication study was to identify the key drivers and mitigating factors that impact the role of Australian Nurse and/or Midwife Consultants. Cross-sectional survey. The study was conducted in a large metropolitan health district in Sydney, Australia. Participants for this study consisted of all Nurse and/or Midwife Consultants working within a health district in New South Wales (NSW). Data were collected by an anonymous online survey. Key drivers and mitigating factors perceived to influence their role were identified using previously implemented instruments. Data were analysed using SPSS version 21. Responses were obtained from 122 Nurse and/or Midwife Consultants. The number of years of experience as a Nurse and/or Midwife Consultant ranged from 6 months to 25.5 years. Personal attributes which included personal motivation and own communication skills were identified as key drivers to role performance with a mean score of 7.7±0.6. Other key drivers included peer support, organisational culture, personal attributes, professional learning, Nurse and/or Midwife Consultant experience, and collaborative relationships. Of the 14 mitigating factors to the role, the most common factors were lack of resources to set up and develop the role (2.6 ± 0.9), lack of secretarial support (2.6 ± 1.1), lack of managerial support (2.45 ± 1.1), and lack of understanding of the role by other health professionals (2.40 ± 0.8). Understanding the key drivers and mitigating factors that influence the role of the Nurse and/or Midwife Consultant is important for healthcare managers. Given the changing landscape of nursing and midwifery practice, organisational strategies to provide ongoing support to address the mitigating factors are urgently needed. It is pivotal that nursing management implement strategies to empower Nurse and/or Midwife Consultants to perform and reach their potential to deliver advanced nursing care.

Natural variation in germination responses of Arabidopsis to seasonal cues and their associated physiological mechanisms

PubMed Central

Barua, Deepak; Butler, Colleen; Tisdale, Tracy E.; Donohue, Kathleen

2012-01-01

Background and Aims Despite the intense interest in phenological adaptation to environmental change, the fundamental character of natural variation in germination is almost entirely unknown. Specifically, it is not known whether different genotypes within a species are germination specialists to particular conditions, nor is it known what physiological mechanisms of germination regulation vary in natural populations and how they are associated with responses to particular environmental factors. Methods We used a set of recombinant inbred genotypes of Arabidopsis thaliana, in which linkage disequilibrium has been disrupted over seven generations, to test for genetic variation and covariation in germination responses to distinct environmental factors. We then examined physiological mechanisms associated with those responses, including seed-coat permeability and sensitivity to the phytohormones gibberellic acid (GA) and abscisic acid (ABA). Key Results Genetic variation for germination was environment-dependent, but no evidence for specialization of germination to different conditions was found. Hormonal sensitivities also exhibited significant genetic variation, but seed-coat properties did not. GA sensitivity was associated with germination responses to multiple environmental factors, but seed-coat permeability and ABA sensitivity were associated with specific germination responses, suggesting that an evolutionary change in GA sensitivity could affect germination in multiple environments, but that of ABA sensitivity may affect germination under more restricted conditions. Conclusions The physiological mechanisms of germination responses to specific environmental factors therefore can influence the ability to adapt to diverse seasonal environments encountered during colonization of new habitats or with future predicted climate change. PMID:22012958

'They think it's all up to the girls': gender, risk and responsibility for contraception.

PubMed

Brown, Sally

2015-01-01

Much research suggests that attitudes towards responsibility for use of contraception amongst young people are strongly gendered. However, decision making, if 'decisions' happen at all, is bound up with notions of hegemonic masculine and feminine roles as well as factors concerning relationship status. Data from two earlier qualitative studies were re-analysed with an emphasis on findings related to gender and responsibility for use of contraception. The first study investigated unintended conceptions amongst 16-20-year-old women. Interviews focused on knowledge and views about contraception, sex education and sexual health services. The second study involved focus groups with two groups of 14-18-year-old men to explore their views on sex education, sexual health and contraception. Almost all the young women said that young men viewed contraception as 'not their job'. In contrast, the young men thought that responsibility should be shared. The key issue, however, related to relationship status, with decision-making being shared in long-term relationships. There are some gender differences in accounting for decisions about use of contraception, however the key issue revolves around relationship status.

The Nature of Experiences Responsible for the Generation and Maintenance of Interest in STEM

ERIC Educational Resources Information Center

Maltese, Adam V.; Melki, Christina S.; Wiebke, Heidi L.

2014-01-01

Previous research has established the importance of early interest in STEM as a key factor in persistence. Our current research builds on this foundation and extends it to add more detail to understanding the types of experiences that trigger and maintain interest in science, technology, engineering, and mathematics (STEM). Using survey data from…

Differentially expressed drought-responsive genes in Malus sieversii roots may contribute to this species' adaptation to arid environments

USDA-ARS?s Scientific Manuscript database

Understanding naturally evolved adaptation to arid climates may be a key factor in developing crops that can thrive during extreme climate fluctuations. Malus sieversii (Ledeb.) M. Roem. is a wild apple species that has adapted to harsh environments in Kazakhstan, including extreme cold and dry reg...

Sharing the Load: Understanding the Roles of Academics and Host Supervisors in Work-Integrated Learning

ERIC Educational Resources Information Center

Winchester-Seeto, Theresa; Rowe, Anna; Mackaway, Jacqueline

2016-01-01

Student supervision is a key factor underpinning the success of work-integrated learning programs. Supervisory responsibilities can be shared across a number of stakeholders including university staff and host/workplace supervisors. While there have been attempts to understand the roles played by each of these stakeholders, little research has…

Fire effects on water quality: a synthesis of response regulating factors among contrasting ecosystems

Treesearch

Katherine J. Elliott; James M. Vose

2006-01-01

The key components of watershed processes are inputs in precipitation, interactions of vegetation, soil and water including evapotranspiration (water yield), overland flow (erosion), and storage and filtering (nutrients), and outputs in streamflow. Fire effects occur at the vegetation-soil interface and can result in altering overland flow and infiltration rate of...

Characterization of clostridium perfringens netB+tpel+ type A atrains isolated from necrotic enteritis-afflicted broiler chickens

USDA-ARS?s Scientific Manuscript database

Clostridium perfringens (CP) Type A strains are the key etiological factor in induction of necrotic enteritis (NE), one of the important enteric diseases in poultry, responsible for the annual loss of $ 6 billions to worldwide poultry industry. Several CP toxin genes were found to be critical in the...

Retrofitting Bureaucracy: Factors Influencing Charter Schools' Access to Federal Entitlement Programs

ERIC Educational Resources Information Center

Rhim, Lauren Morando; Brinson, Dana

2010-01-01

Charter school laws and successful charter schools have been identified as key elements of bold initiatives to turn around chronically low-achieving public schools. Yet, charter schools operate in a policy space that was not constructed for them, a space in which public schools are primarily a state responsibility, but are markedly influenced by…

Assessment of Education for Sustainable Development in Universities in Costa Rica: Implications for Latin America and the Caribbean

ERIC Educational Resources Information Center

Garcia, Jairo H.

2010-01-01

Higher Education is a key factor for social change influencing future decision-makers in business, education, politics and science. As such, sustainable development requires creating awareness amongst these decision-makers of their responsibilities and opportunities in this area. Higher education for sustainable development is championed in…

Opting out of the Bill: Voluntary Adequacy Funding in Maryland

ERIC Educational Resources Information Center

Finch, Maida A.; Goff, Peter; Houck, Eric

2016-01-01

The key to anticipating local response to state finance policy is to bridge knowledge of the state context with the specifications of the individual reform. Yet it is precisely this unique blend of social, political, and economic factors in any given state that makes the impact of school finance reforms difficult to predict, especially as these…

Navigating the Challenges of Becoming a Culturally Responsive Teacher: Supportive Networking May Be the Key

ERIC Educational Resources Information Center

Nilsson, Nina L.; Kong, Ailing; Hubert, Shantel

2016-01-01

Research shows graduates of teacher education programs do not always transfer, or apply, the best practices they learn to instructional practice due to factors related to course features, the student, and workplace environment (e.g., Brown & Bentley, 2004; de Jong et al., 2010). This study examined the challenges a secondary-level English…

The role of hemocytes in A. gambiae antiplasmodial immunity

PubMed Central

Ramirez, Jose Luis; Garver, Lindsey S.; Brayner, Fábio André; Alves, Luiz Carlos; Rodrigues, Janneth; Molina-Cruz, Alvaro; Barillas-Mury, Carolina

2013-01-01

Hemocytes synthesize key components of the mosquito complement-like system, but their role in the activation of antiplasmodial responses has not been established. The effect of activating Toll signaling in hemocytes on Plasmodium survival was investigated by transferring hemocytes or cell-free hemolymph from donor mosquitoes in which the suppressor cactus was silenced. These transfers greatly enhanced antiplasmodial immunity, indicating that hemocytes are active players in the activation of the complement-like system, through an effector(s) regulated by the Toll pathway. A comparative analysis of hemocyte populations between susceptible (S) G3 and the refractory (R) L3-5 A. gambiae mosquito strains did not reveal significant differences under basal conditions or in response to Plasmodium berghei infection. The response of S mosquitoes to different Plasmodium species revealed similar kinetics following infection with P. berghei, P. yoelii or P. falciparum, but the strength of the priming response was stronger in less compatible mosquito-parasite pairs. The Toll, Imd, STAT or JNK signaling cascades were not essential for the production of hemocyte differentiation factor (HDF) in response to P. berghei infection, but disruption of Toll, STAT or JNK abolished hemocyte differentiation in response to HDF. We conclude that hemocytes are key mediators of A. gambiae antiplasmodial responses. PMID:23886925

Setting Foundations for Developing Disaster Response Metrics.

PubMed

Abir, Mahshid; Bell, Sue Anne; Puppala, Neha; Awad, Osama; Moore, Melinda

2017-08-01

There are few reported efforts to define universal disaster response performance measures. Careful examination of responses to past disasters can inform the development of such measures. As a first step toward this goal, we conducted a literature review to identify key factors in responses to 3 recent events with significant loss of human life and economic impact: the 2003 Bam, Iran, earthquake; the 2004 Indian Ocean tsunami; and the 2010 Haiti earthquake. Using the PubMed (National Library of Medicine, Bethesda, MD) database, we identified 710 articles and retained 124 after applying inclusion and exclusion criteria. Seventy-two articles pertained to the Haiti earthquake, 38 to the Indian Ocean tsunami, and 14 to the Bam earthquake. On the basis of this review, we developed an organizational framework for disaster response performance measurement with 5 key disaster response categories: (1) personnel, (2) supplies and equipment, (3) transportation, (4) timeliness and efficiency, and (5) interagency cooperation. Under each of these, and again informed by the literature, we identified subcategories and specific items that could be developed into standardized performance measures. The validity and comprehensiveness of these measures can be tested by applying them to other recent and future disaster responses, after which standardized performance measures can be developed through a consensus process. (Disaster Med Public Health Preparedness. 2017;11:505-509).

Bovine somatotropin and lactation: from basic science to commercial application.

PubMed

Bauman, D E

1999-10-01

Bovine somatotropin (bST) results in increased milk yield and an unprecedented improvement in efficiency. Beginning in the 1930s to present day, investigations have examined animal-related factors such as nutrition, bioenergetics, metabolism, health and well being and consumer-related factors such as milk quality, manufacturing characteristics, and product safety. Overall, bST is a homeorhetic control involved in orchestrating many physiological processes. Direct effects involve adaptations in many tissues and the metabolism of all nutrient classes--carbohydrates, lipids, protein, and minerals. Mechanisms include alterations in key enzymes, intracellular signal transduction systems, and tissue response to homeostatic signals. Indirect effects involve the mammary gland and are thought to be mediated by the insulin-like growth factor (IGF) system. Specific changes include increased cellular rates of milk synthesis and enhanced maintenance of secretory cells. Indirect effects are modulated by environment and management factors, especially nutritional status. This modulation is a central component in allowing ST to play a key role in regulating nutrient utilization across a range of physiological situations. U.S. commercial use began in 1994, and adoption has been extensive. From a consumer perspective, bST was unique, and special interest groups loudly predicted dire consequences. However, introduction of bST had no impact on milk consumption, and milk labeled as recombinant bST-free occupies a minor niche market. From a producer perspective, commercial use verified scientific studies and enhanced net farm income. Overall, ST is a key homeorhetic control regulating nutrient partitioning, and the ST/IGF system plays a key role in animal performance and well being across a range of physiological situations.

Public Health Works: Blood Donation in Urban China

PubMed Central

Adams, Vincanne; Erwin, Kathleen; Le, Phuoc V

2009-01-01

Recent shifts in the global health infrastructure warrant consideration of the value and effectiveness of national public health campaigns. These shifts include the globalization of pharmaceutical research, the rise of NGO-funded health interventions, and the rise of biosecurity models of international health. We argue that although these trends have arisen as worthwhile responses to actual health needs, it is important to remember the key role that public health campaigns can play in the promotion of national health, especially in developing nations. Focusing on an example set by China in response to a public health crisis surrounding the national need for a clean and adequate blood supply and the inadvertent spread of HIV by way of blood donation in the early 19902, we argue that there is an important role for strong national public health programs. We also identify the key factors that enabled China’s response to this bourgeoning epidemic to be, in the end, largely successful. PMID:19058887

Workforce Perceptions of Hospital Safety Culture: Development and Validation of the Patient Safety Climate in Healthcare Organizations Survey

PubMed Central

Singer, Sara; Meterko, Mark; Baker, Laurence; Gaba, David; Falwell, Alyson; Rosen, Amy

2007-01-01

Objective To describe the development of an instrument for assessing workforce perceptions of hospital safety culture and to assess its reliability and validity. Data Sources/Study Setting Primary data collected between March 2004 and May 2005. Personnel from 105 U.S. hospitals completed a 38-item paper and pencil survey. We received 21,496 completed questionnaires, representing a 51 percent response rate. Study Design Based on review of existing safety climate surveys, we developed a list of key topics pertinent to maintaining a culture of safety in high-reliability organizations. We developed a draft questionnaire to address these topics and pilot tested it in four preliminary studies of hospital personnel. We modified the questionnaire based on experience and respondent feedback, and distributed the revised version to 42,249 hospital workers. Data Collection We randomly divided respondents into derivation and validation samples. We applied exploratory factor analysis to responses in the derivation sample. We used those results to create scales in the validation sample, which we subjected to multitrait analysis (MTA). Principal Findings We identified nine constructs, three organizational factors, two unit factors, three individual factors, and one additional factor. Constructs demonstrated substantial convergent and discriminant validity in the MTA. Cronbach's α coefficients ranged from 0.50 to 0.89. Conclusions It is possible to measure key salient features of hospital safety climate using a valid and reliable 38-item survey and appropriate hospital sample sizes. This instrument may be used in further studies to better understand the impact of safety climate on patient safety outcomes. PMID:17850530

Parasympathetic nervous system activity predicts mood repair use and its effectiveness among adolescents with and without histories of major depression

PubMed Central

Yaroslavsky, Ilya; Rottenberg, Jonathan; Bylsma, Lauren M.; Jennings, J. Richard; George, Charles; Baji, Ildikó; Benák, István; Dochnal, Roberta; Halas, Kitti; Kapornai, Krisztina; Kiss, Enikő; Makai, Attila; Varga, Hedvig; Vetró, Ágnes; Kovacs, Maria

2016-01-01

Depressive disorders that onset in the juvenile years have been linked to far reaching adverse consequences, making it imperative to elucidate key mechanisms and contributory factors. Excessive use of regulatory responses that exacerbate sadness (maladaptive mood repair) or insufficient use of regulatory responses that reduce it (adaptive mood repair) may reflect behavioral mechanisms of depression risk. Cardiac vagal control, indexed by patterns of respiratory sinus arrhythmia (RSA), has received attention as a putative physiological risk factor for depression. Although mood repair and RSA are related, the nature of this relationship is not well characterized in the context of depression risk. Therefore, we tested alternative models of the relationships between RSA patterns (at rest and in response to a sad film), trait mood repair, and the effectiveness of a mood repair response in the laboratory (state mood repair) among adolescents with depression histories (n=210) and emotionally healthy peers (n=161). In our data, a mediation model best explained the association between the key constructs: Adolescents with normative RSA patterns exhibited lower levels of depression and trait maladaptive mood repair, and benefited more from instructed (state) mood repair in the laboratory. By contrast, adolescents with atypical RSA patterns exhibited higher levels of depression and dispositional maladaptive mood repair, which, in turn, mediated the relations of RSA patterns and depression symptoms. Atypical RSA patterns also predicted reduced benefits from laboratory mood repair. PMID:26950752

Uncovering the Role of RNA-Binding Proteins in Gene Expression in the Immune System

PubMed Central

Díaz-Muñoz, Manuel D.; Turner, Martin

2018-01-01

Fighting external pathogens requires an ever-changing immune system that relies on tight regulation of gene expression. Transcriptional control is the first step to build efficient responses while preventing immunodeficiencies and autoimmunity. Post-transcriptional regulation of RNA editing, location, stability, and translation are the other key steps for final gene expression, and they are all controlled by RNA-binding proteins (RBPs). Nowadays we have a deep understanding of how transcription factors control the immune system but recent evidences suggest that post-transcriptional regulation by RBPs is equally important for both development and activation of immune responses. Here, we review current knowledge about how post-transcriptional control by RBPs shapes our immune system and discuss the perspective of RBPs being the key players of a hidden immune cell epitranscriptome. PMID:29875770

A transcriptomic analysis of bermudagrass (Cynodon dactylon) provides novel insights into the basis of low temperature tolerance.

PubMed

Chen, Liang; Fan, Jibiao; Hu, Longxing; Hu, Zhengrong; Xie, Yan; Zhang, Yingzi; Lou, Yanhong; Nevo, Eviatar; Fu, Jinmin

2015-09-11

Cold stress is regarded as a key factor limiting widespread use for bermudagrass (Cynodon dactylon). Therefore, to improve cold tolerance for bermudagrass, it is urgent to understand molecular mechanisms of bermudagrass response to cold stress. However, our knowledge about the molecular responses of this species to cold stress is largely unknown. The objective of this study was to characterize the transcriptomic response to low temperature in bermudagrass by using RNA-Seq platform. Ten cDNA libraries were generated from RNA samples of leaves from five different treatments in the cold-resistant (R) and the cold-sensitive (S) genotypes, including 4 °C cold acclimation (CA) for 24 h and 48 h, freezing (-5 °C) treatments for 4 h with or without prior CA, and controls. When subjected to cold acclimation, global gene expressions were initiated more quickly in the R genotype than those in the S genotype. The R genotype activated gene expression more effectively in response to freezing temperature after 48 h CA than the S genotype. The differentially expressed genes were identified as low temperature sensing and signaling-related genes, functional proteins and transcription factors, many of which were specifically or predominantly expressed in the R genotype under cold treatments, implying that these genes play important roles in the enhanced cold hardiness of bermudagrass. KEGG pathway enrichment analysis for DEGs revealed that photosynthesis, nitrogen metabolism and carbon fixation pathways play key roles in bermudagrass response to cold stress. The results of this study may contribute to our understanding the molecular mechanism underlying the responses of bermudagrass to cold stress, and also provide important clues for further study and in-depth characterization of cold-resistance breeding candidate genes in bermudagrass.

Metabolic and stress-related roles of prolactin-releasing peptide.

PubMed

Onaka, Tatsushi; Takayanagi, Yuki; Leng, Gareth

2010-05-01

In the modern world, improvements in human health can be offset by unhealthy lifestyle factors, including the deleterious consequences of stress and obesity. For energy homeostasis, humoral factors and neural afferents from the gastrointestinal tract, in combination with long-term nutritional signals, communicate information to the brain to regulate energy intake and expenditure. Energy homeostasis and stress interact with each other, and stress affects both food intake and energy expenditure. Prolactin-releasing peptide, synthesized in discrete neuronal populations in the hypothalamus and brainstem, plays an important role in integrating these responses. This review describes how prolactin-releasing peptide neurons receive information concerning both internal metabolic states and environmental conditions, and play a key role in energy homeostasis and stress responses. 2010 Elsevier Ltd. All rights reserved.

A survey of the governance capacity of national public health associations to enhance population health.

PubMed

Chauvin, James; Shukla, Mahesh; Rice, James; Rispel, Laetitia

2016-03-11

National public health associations (PHAs) are key partners with governments and communities to improve, protect and promote the public's health. Governance and organizational capacity are among the key determinants of a PHA's effectiveness as an advocate for appropriate public health policies and practice. During 2014, the World Federation of Public Health Associations (WFPHA) conducted an on-line survey of its 82 PHA members, to identify the state of organizational governance of national public health associations, as well as the factors that influence optimal organizational governance. The survey consisted of 13 questions and focused on the main elements of organizational governance: cultivating accountability; engaging stakeholders; setting shared direction; stewarding resources; and, continuous governance enhancement. Four questions included a qualitative open-ended response for additional comments. The survey data were analyzed using Microsoft Excel. The qualitative data was analyzed using thematic content analysis Responses were received from 62 PHAs, constituting a 75.6 % response rate. The two most important factors that support governance effectiveness were a high degree of integrity and ethical behavior of the PHA's leaders (77 %) and the competence of people serving on the PHA's governing body (76 %). The lack of financial resources was considered as the most important factor that negatively affected organizational governance effectiveness (73 %). The lack of mentoring for future PHA leaders; ineffective or incompetent leadership; lack of understanding about good governance practices; and lack of accurate information for strategic planning were identified as factors influencing PHA governance effectiveness. Critical elements for PHA sustainability included diversity, gender-responsiveness and inclusive governance practices, and strategies to build the future generation of public health leaders. National PHA have a responsibility to put into place the practices and infrastructure that enhance organizational governance. This will enhance their ability to be effective advocates for policies and practices that enhance, protect and promote the public's health. The WFPHA has an important role to play in providing the technical assistance and financial resources to assist PHAs in attaining and sustaining a higher level of governance capacity.

From Genes to Networks: Characterizing Gene-Regulatory Interactions in Plants.

PubMed

Kaufmann, Kerstin; Chen, Dijun

2017-01-01

Plants, like other eukaryotes, have evolved complex mechanisms to coordinate gene expression during development, environmental response, and cellular homeostasis. Transcription factors (TFs), accompanied by basic cofactors and posttranscriptional regulators, are key players in gene-regulatory networks (GRNs). The coordinated control of gene activity is achieved by the interplay of these factors and by physical interactions between TFs and DNA. Here, we will briefly outline recent technological progress made to elucidate GRNs in plants. We will focus on techniques that allow us to characterize physical interactions in GRNs in plants and to analyze their regulatory consequences. Targeted manipulation allows us to test the relevance of specific gene-regulatory interactions. The combination of genome-wide experimental approaches with mathematical modeling allows us to get deeper insights into key-regulatory interactions and combinatorial control of important processes in plants.

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

IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma

PubMed Central

Svalina, Matthew N.; Kikuchi, Ken; Abraham, Jinu; Lal, Sangeet; Davare, Monika A.; Settelmeyer, Teagan P.; Young, Michael C.; Peckham, Jennifer L.; Cho, Yoon-Jae; Michalek, Joel E.; Hernandez, Brian S.; Berlow, Noah E.; Jackson, Melanie; Guillaume, Daniel J.; Selden, Nathan R.; Bigner, Darell D.; Nazemi, Kellie J.; Green, Sarah C.; Corless, Christopher L.; Gultekin, Sakir; Mansoor, Atiya; Rubin, Brian P.; Woltjer, Randall; Keller, Charles

2016-01-01

Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA), and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri-/sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in MYC amplified medulloblastoma prioritized IGF1R inhibitors. Together, our studies identify IGF1R as a high value target for clinical trials in high risk medulloblastoma. PMID:27255663

Risk factors for dental problems: Recommendations for oral health in infancy.

PubMed

Wagner, Yvonne; Heinrich-Weltzien, Roswitha

2017-11-01

Primary care providers, gynaecologists and paediatricians have to be aware of the importance of oral health in infancy and possible consequences for child's development, growth, health and quality of life. Oral diseases, particularly dental caries, developmental defects of the dental tissues and periodontal or orthodontic issues have a complex and interrelated aetiology with common, primarily behavioral based risk factors. A sugar-rich diet is the key risk factor with detrimental consequences for general and oral health, particularly in combination with an insufficient oral hygiene. Therefore, daily tooth brushing with fluoride toothpaste and reducing of sugar intake are the key pillars to prevent oral diseases, including a positive effect on numerous chronic diseases. Future preventive approaches should focus on pregnant women and mothers of infants with a common vision of health and a shared responsibility for children's oral health care to promote healthy lifestyles and self-care practices in families. Copyright © 2017 Elsevier B.V. All rights reserved.

IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma.

PubMed

Svalina, Matthew N; Kikuchi, Ken; Abraham, Jinu; Lal, Sangeet; Davare, Monika A; Settelmeyer, Teagan P; Young, Michael C; Peckham, Jennifer L; Cho, Yoon-Jae; Michalek, Joel E; Hernandez, Brian S; Berlow, Noah E; Jackson, Melanie; Guillaume, Daniel J; Selden, Nathan R; Bigner, Darell D; Nazemi, Kellie J; Green, Sarah C; Corless, Christopher L; Gultekin, Sakir; Mansoor, Atiya; Rubin, Brian P; Woltjer, Randall; Keller, Charles

2016-06-03

Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA), and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri-/sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in MYC amplified medulloblastoma prioritized IGF1R inhibitors. Together, our studies identify IGF1R as a high value target for clinical trials in high risk medulloblastoma.

Systems analysis of transcriptome data provides new hypotheses about Arabidopsis root response to nitrate treatments

PubMed Central

Canales, Javier; Moyano, Tomás C.; Villarroel, Eva; Gutiérrez, Rodrigo A.

2014-01-01

Nitrogen (N) is an essential macronutrient for plant growth and development. Plants adapt to changes in N availability partly by changes in global gene expression. We integrated publicly available root microarray data under contrasting nitrate conditions to identify new genes and functions important for adaptive nitrate responses in Arabidopsis thaliana roots. Overall, more than 2000 genes exhibited changes in expression in response to nitrate treatments in Arabidopsis thaliana root organs. Global regulation of gene expression by nitrate depends largely on the experimental context. However, despite significant differences from experiment to experiment in the identity of regulated genes, there is a robust nitrate response of specific biological functions. Integrative gene network analysis uncovered relationships between nitrate-responsive genes and 11 highly co-expressed gene clusters (modules). Four of these gene network modules have robust nitrate responsive functions such as transport, signaling, and metabolism. Network analysis hypothesized G2-like transcription factors are key regulatory factors controlling transport and signaling functions. Our meta-analysis highlights the role of biological processes not studied before in the context of the nitrate response such as root hair development and provides testable hypothesis to advance our understanding of nitrate responses in plants. PMID:24570678

Multiple response optimization for higher dimensions in factors and responses

DOE PAGES

Lu, Lu; Chapman, Jessica L.; Anderson-Cook, Christine M.

2016-07-19

When optimizing a product or process with multiple responses, a two-stage Pareto front approach is a useful strategy to evaluate and balance trade-offs between different estimated responses to seek optimum input locations for achieving the best outcomes. After objectively eliminating non-contenders in the first stage by looking for a Pareto front of superior solutions, graphical tools can be used to identify a final solution in the second subjective stage to compare options and match with user priorities. Until now, there have been limitations on the number of response variables and input factors that could effectively be visualized with existing graphicalmore » summaries. We present novel graphical tools that can be more easily scaled to higher dimensions, in both the input and response spaces, to facilitate informed decision making when simultaneously optimizing multiple responses. A key aspect of these graphics is that the potential solutions can be flexibly sorted to investigate specific queries, and that multiple aspects of the solutions can be simultaneously considered. As a result, recommendations are made about how to evaluate the impact of the uncertainty associated with the estimated response surfaces on decision making with higher dimensions.« less

Heat shock factor-1 modulates p53 activity in the transcriptional response to DNA damage

PubMed Central

Logan, Ian R.; McNeill, Hesta V.; Cook, Susan; Lu, Xiaohong; Meek, David W.; Fuller-Pace, Frances V.; Lunec, John; Robson, Craig N.

2009-01-01

Here we define an important role for heat shock factor 1 (HSF1) in the cellular response to genotoxic agents. We demonstrate for the first time that HSF1 can complex with nuclear p53 and that both proteins are co-operatively recruited to p53-responsive genes such as p21. Analysis of natural and synthetic cis elements demonstrates that HSF1 can enhance p53-mediated transcription, whilst depletion of HSF1 reduces the expression of p53-responsive transcripts. We find that HSF1 is required for optimal p21 expression and p53-mediated cell-cycle arrest in response to genotoxins while loss of HSF1 attenuates apoptosis in response to these agents. To explain these novel properties of HSF1 we show that HSF1 can complex with DNA damage kinases ATR and Chk1 to effect p53 phosphorylation in response to DNA damage. Our data reveal HSF1 as a key transcriptional regulator in response to genotoxic compounds widely used in the clinical setting, and suggest that HSF1 will contribute to the efficacy of these agents. PMID:19295133

Curcumin ameliorates autoimmune diabetes. Evidence in accelerated murine models of type 1 diabetes

PubMed Central

Castro, C N; Barcala Tabarrozzi, A E; Winnewisser, J; Gimeno, M L; Antunica Noguerol, M; Liberman, A C; Paz, D A; Dewey, R A; Perone, M J

2014-01-01

Type 1 diabetes (T1DM) is a T cell-mediated autoimmune disease that selectively destroys pancreatic β cells. The only possible cure for T1DM is to control autoimmunity against β cell-specific antigens. We explored whether the natural compound curcumin, with anti-oxidant and anti-inflammatory activities, might down-regulate the T cell response that destroys pancreatic β cells to improve disease outcome in autoimmune diabetes. We employed two accelerated autoimmune diabetes models: (i) cyclophosphamide (CYP) administration to non-obese diabetic (NOD) mice and (ii) adoptive transfer of diabetogenic splenocytes into NODscid mice. Curcumin treatment led to significant delay of disease onset, and in some instances prevented autoimmune diabetes by inhibiting pancreatic leucocyte infiltration and preserving insulin-expressing cells. To investigate the mechanisms of protection we studied the effect of curcumin on key immune cell populations involved in the pathogenesis of the disease. Curcumin modulates the T lymphocyte response impairing proliferation and interferon (IFN)-γ production through modulation of T-box expressed in T cells (T-bet), a key transcription factor for proinflammatory T helper type 1 (Th1) lymphocyte differentiation, both at the transcriptional and translational levels. Also, curcumin reduces nuclear factor (NF)-κB activation in T cell receptor (TCR)-stimulated NOD lymphocytes. In addition, curcumin impairs the T cell stimulatory function of dendritic cells with reduced secretion of proinflammatory cytokines and nitric oxide (NO) and low surface expression of co-stimulatory molecules, leading to an overall diminished antigen-presenting cell activity. These in-vitro effects correlated with ex-vivo analysis of cells obtained from curcumin-treated mice during the course of autoimmune diabetes. These findings reveal an effective therapeutic effect of curcumin in autoimmune diabetes by its actions on key immune cells responsible for β cell death. PMID:24628444

Cortistatin Is a Key Factor Regulating the Sex-Dependent Response of the GH and Stress Axes to Fasting in Mice.

PubMed

Cordoba-Chacón, José; Gahete, Manuel D; Pozo-Salas, Ana I; de Lecea, Luis; Castaño, Justo P; Luque, Raúl M

2016-07-01

Cortistatin (CORT) shares high structural and functional similarities with somatostatin (SST) but displays unique sex-dependent pituitary actions. Indeed, although female CORT-knockout (CORT-KO) mice exhibit enhanced GH expression/secretion, Proopiomelanocortin expression, and circulating ACTH/corticosterone/ghrelin levels, male CORT-KO mice only display increased plasma GH/corticosterone levels. Changes in peripheral ghrelin and SST (rather than hypothalamic levels) seem to regulate GH/ACTH axes in CORT-KOs under fed conditions. Because changes in GH/ACTH axes during fasting provide important adaptive mechanisms, we sought to determine whether CORT absence influences GH/ACTH axes during fasting. Accordingly, fed and fasted male/female CORT-KO were compared with littermate controls. Fasting increased circulating GH levels in male/female controls but not in CORT-KO, suggesting that CORT can be a relevant regulator of GH secretion during fasting. However, GH levels were already higher in CORT-KO than in controls in fed state, which might preclude a further elevation in GH levels. Interestingly, although fasting-induced pituitary GH expression was elevated in both male/female controls, GH expression only increased in fasted female CORT-KOs, likely owing to specific changes observed in key factors controlling somatotrope responsiveness (ie, circulating ghrelin and IGF-1, and pituitary GHRH and ghrelin receptor expression). Fasting increased corticosterone levels in control and, most prominently, in CORT-KO mice, which might be associated with a desensitization to SST signaling and to an augmentation in CRH and ghrelin-signaling regulating corticotrope function. Altogether, these results provide compelling evidence that CORT plays a key, sex-dependent role in the regulation of the GH/ACTH axes in response to fasting.

Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer

PubMed Central

Block, Matthew S.; Charbonneau, Bridget; Vierkant, Robert A.; Fogarty, Zachary; Bamlet, William R.; Pharoah, Paul D.P.; Chenevix-Trench, Georgia; Rossing, Mary Anne; Cramer, Daniel; Pearce, Celeste Leigh; Schildkraut, Joellen; Menon, Usha; Kjaer, Susanne K.; Levine, Douglas A.; Gronwald, Jacek; Culver, Hoda Anton; Whittemore, Alice S.; Karlan, Beth Y.; Lambrechts, Diether; Wentzensen, Nicolas; Kupryjanczyk, Jolanta; Chang-Claude, Jenny; Bandera, Elisa V.; Hogdall, Estrid; Heitz, Florian; Kaye, Stanley B.; Fasching, Peter A.; Campbell, Ian; Goodman, Marc T.; Pejovic, Tanja; Bean, Yukie T.; Hays, Laura E.; Lurie, Galina; Eccles, Diana; Hein, Alexander; Beckmann, Matthias W.; Ekici, Arif B.; Paul, James; Brown, Robert; Flanagan, James M.; Harter, Philipp; du Bois, Andreas; Schwaab, Ira; Hogdall, Claus K.; Lundvall, Lene; Olson, Sara H.; Orlow, Irene; Paddock, Lisa E.; Rudolph, Anja; Eilber, Ursula; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K.; Ziolkowska-Seta, Izabela; Brinton, Louise A.; Yang, Hannah; Garcia-Closas, Montserrat; Despierre, Evelyn; Lambrechts, Sandrina; Vergote, Ignace; Walsh, Christine S.; Lester, Jenny; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H.; Ziogas, Argyrios; Lubiński, Jan; Cybulski, Cezary; Menkiszak, Janusz; Jensen, Allan; Gayther, Simon A.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Berchuck, Andrew; Wu, Anna H.; Pike, Malcolm C.; Van Den Berg, David; Terry, Kathryn L.; Vitonis, Allison F.; Ramirez, Starr M.; Rider, David N.; Knutson, Keith L.; Sellers, Thomas A.; Phelan, Catherine M.; Doherty, Jennifer A.; Johnatty, Sharon E.; deFazio, Anna; Song, Honglin; Tyrer, Jonathan; Kalli, Kimberly R.; Fridley, Brooke L.; Cunningham, Julie M.; Goode, Ellen L.

2014-01-01

Survival in epithelial ovarian cancer (EOC) is influenced by the host immune response, yet the key genetic determinants of inflammation and immunity that impact prognosis are not known. The nuclear factor-kappa B (NF-κB) transcription factor family plays an important role in many immune and inflammatory responses, including the response to cancer. We studied common inherited variation in 210 genes in the NF-κB family in 10,084 patients with invasive EOC (5,248 high grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous) from the Ovarian Cancer Association Consortium. Associations between genotype and overall survival were assessed using Cox regression for all patients and by major histology, adjusting for known prognostic factors and correcting for multiple testing (threshold for statistical significance—p < 2.5×10−5). Results were statistically significant when assessed for patients of a single histology. Key associations were with CARD11 (caspase recruitment domain family, member 11) rs41324349 in patients with mucinous EOC (HR 1.82, 95% CI 1.41–2.35, p=4.13×10−6) and TNFRSF13B (tumor necrosis factor receptor superfamily, member 13B) rs7501462 in patients with endometrioid EOC (HR 0.68, 95% CI 0.56–0.82, p=2.33×10−5). Other associations of note included TRAF2 (TNF receptor-associated factor 2) rs17250239 in patients with high-grade serous EOC (HR 0.84, 95% CI 0.77–0.92, p=6.49×10−5) and PLCG1 (phospholipase C, gamma 1) rs11696662 in patients with clear cell EOC (HR 0.43, 95% CI 0.26–0.73, p=4.56×10−4). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies. PMID:24740199

Variation in NF-κB signaling pathways and survival in invasive epithelial ovarian cancer.

PubMed

Block, Matthew S; Charbonneau, Bridget; Vierkant, Robert A; Fogarty, Zachary; Bamlet, William R; Pharoah, Paul D P; Rossing, Mary Anne; Cramer, Daniel; Pearce, Celeste Leigh; Schildkraut, Joellen; Menon, Usha; Kjaer, Susanne K; Levine, Douglas A; Gronwald, Jacek; Culver, Hoda Anton; Whittemore, Alice S; Karlan, Beth Y; Lambrechts, Diether; Wentzensen, Nicolas; Kupryjanczyk, Jolanta; Chang-Claude, Jenny; Bandera, Elisa V; Hogdall, Estrid; Heitz, Florian; Kaye, Stanley B; Fasching, Peter A; Campbell, Ian; Goodman, Marc T; Pejovic, Tanja; Bean, Yukie T; Hays, Laura E; Lurie, Galina; Eccles, Diana; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Paul, James; Brown, Robert; Flanagan, James M; Harter, Philipp; du Bois, Andreas; Schwaab, Ira; Hogdall, Claus K; Lundvall, Lene; Olson, Sara H; Orlow, Irene; Paddock, Lisa E; Rudolph, Anja; Eilber, Ursula; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K; Ziolkowska-Seta, Izabela; Brinton, Louise A; Yang, Hannah; Garcia-Closas, Montserrat; Despierre, Evelyn; Lambrechts, Sandrina; Vergote, Ignace; Walsh, Christine S; Lester, Jenny; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H; Ziogas, Argyrios; Lubiński, Jan; Cybulski, Cezary; Menkiszak, Janusz; Jensen, Allan; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Aleksandra; Berchuck, Andrew; Wu, Anna H; Pike, Malcolm C; Van Den Berg, David; Terry, Kathryn L; Vitonis, Allison F; Ramirez, Starr M; Rider, David N; Knutson, Keith L; Sellers, Thomas A; Phelan, Catherine M; Doherty, Jennifer A; Johnatty, Sharon E; deFazio, Anna; Song, Honglin; Tyrer, Jonathan; Kalli, Kimberly R; Fridley, Brooke L; Cunningham, Julie M; Goode, Ellen L

2014-07-01

Survival in epithelial ovarian cancer (EOC) is influenced by the host immune response, yet the key genetic determinants of inflammation and immunity that affect prognosis are not known. The nuclear factor-κB (NF-κB) transcription factor family plays an important role in many immune and inflammatory responses, including the response to cancer. We studied common inherited variation in 210 genes in the NF-κB family in 10,084 patients with invasive EOC (5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous) from the Ovarian Cancer Association Consortium. Associations between genotype and overall survival were assessed using Cox regression for all patients and by major histology, adjusting for known prognostic factors and correcting for multiple testing (threshold for statistical significance, P < 2.5 × 10(-5)). Results were statistically significant when assessed for patients of a single histology. Key associations were with caspase recruitment domain family, member 11 (CARD11) rs41324349 in patients with mucinous EOC [HR, 1.82; 95% confidence interval (CI), 1.41-2.35; P = 4.13 × 10(-6)] and tumor necrosis factor receptor superfamily, member 13B (TNFRSF13B) rs7501462 in patients with endometrioid EOC (HR, 0.68; 95% CI, 0.56-0.82; P = 2.33 × 10(-5)). Other associations of note included TNF receptor-associated factor 2 (TRAF2) rs17250239 in patients with high-grade serous EOC (HR, 0.84; 95% CI, 0.77-0.92; P = 6.49 × 10(-5)) and phospholipase C, gamma 1 (PLCG1) rs11696662 in patients with clear cell EOC (HR, 0.43; 95% CI, 0.26-0.73; P = 4.56 × 10(-4)). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies. ©2014 American Association for Cancer Research.

HIV among people who inject drugs in Central and Eastern Europe and Central Asia: a systematic review with implications for policy

PubMed Central

Jolley, Emma; Rhodes, Tim; Platt, Lucy; Hope, Vivian; Latypov, Alisher; Donoghoe, Martin; Wilson, David

2012-01-01

Background and objectives HIV among people who inject drugs (PWID) is a major public health concern in Eastern and Central Europe and Central Asia. HIV transmission in this group is growing and over 27 000 HIV cases were diagnosed among PWID in 2010 alone. The objective of this systematic review was to examine risk factors associated with HIV prevalence among PWID in Central and Eastern Europe and Central Asia and to describe the response to HIV in this population and the policy environments in which they live. Design A systematic review of peer-reviewed and grey literature addressing HIV prevalence and risk factors for HIV prevalence among PWID and a synthesis of key resources describing the response to HIV in this population. We used a comprehensive search strategy across multiple electronic databases to collect original research papers addressing HIV prevalence and risk factors among PWID since 2005. We summarised the extent of key harm reduction interventions, and using a simple index of ‘enabling’ environment described the policy environments in which they are implemented. Studies reviewed Of the 5644 research papers identified from electronic databases and 40 documents collected from our grey literature search, 70 documents provided unique estimates of HIV and 14 provided multivariate risk factors for HIV among PWID. Results HIV prevalence varies widely, with generally low or medium (<5%) prevalence in Central Europe and high (>10%) prevalence in Eastern Europe. We found evidence for a number of structural factors associated with HIV including gender, socio-economic position and contact with law enforcement agencies. Conclusions The HIV epidemic among PWID in the region is varied, with the greatest burden generally in Eastern Europe. Data suggest that the current response to HIV among PWID is insufficient, and hindered by multiple environmental barriers including restricted access to services and unsupportive policy or social environments. PMID:23087014

Effect of glial cell line-derived neurotrophic factor on behavior and key members of the brain serotonin system in mouse strains genetically predisposed to behavioral disorders.

PubMed

Naumenko, Vladimir S; Bazovkina, Daria V; Semenova, Alina A; Tsybko, Anton S; Il'chibaeva, Tatyana V; Kondaurova, Elena M; Popova, Nina K

2013-12-01

The effect of glial cell line-derived neurotrophic factor (GDNF) on behavior and on the serotonin (5-HT) system of a mouse strain predisposed to depressive-like behavior, ASC/Icg (Antidepressant Sensitive Cataleptics), in comparison with the parental "nondepressive" CBA/Lac mice was studied. Within 7 days after acute administration, GDNF (800 ng, i.c.v.) decreased cataleptic immobility but increased depressive-like behavioral traits in both investigated mouse strains and produced anxiolytic effects in ASC mice. The expression of the gene encoding the key enzyme for 5-HT biosynthesis in the brain, tryptophan hydroxylase-2 (Tph-2), and 5-HT1A receptor gene in the midbrain as well as 5-HT2A receptor gene in the frontal cortex were increased in GDNF-treated ASC mice. At the same time, GDNF decreased 5-HT1A and 5-HT2A receptor gene expression in the hippocampus of ASC mice. GDNF failed to change Tph2, 5-HT1A , or 5-HT2A receptor mRNA levels in CBA mice as well as 5-HT transporter gene expression and 5-HT1A and 5-HT2A receptor functional activity in both investigated mouse strains. The results show 1) a GDNF-induced increase in the expression of key genes of the brain 5-HT system, Tph2, 5-HT1A , and 5-HT2A receptors, and 2) significant genotype-dependent differences in the 5-HT system response to GDNF treatment. The data suggest that genetically defined cross-talk between neurotrophic factors and the brain 5-HT system underlies the variability in behavioral response to GDNF. Copyright © 2013 Wiley Periodicals, Inc.

Cryptochrome 1 interacts with PIF4 to regulate high temperature-mediated hypocotyl elongation in response to blue light.

PubMed

Ma, Dingbang; Li, Xu; Guo, Yongxia; Chu, Jingfang; Fang, Shuang; Yan, Cunyu; Noel, Joseph P; Liu, Hongtao

2016-01-05

Cryptochrome 1 (CRY1) is a blue light receptor that mediates primarily blue-light inhibition of hypocotyl elongation. Very little is known of the mechanisms by which CRY1 affects growth. Blue light and temperature are two key environmental signals that profoundly affect plant growth and development, but how these two abiotic factors integrate remains largely unknown. Here, we show that blue light represses high temperature-mediated hypocotyl elongation via CRY1. Furthermore, CRY1 interacts directly with PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) in a blue light-dependent manner to repress the transcription activity of PIF4. CRY1 represses auxin biosynthesis in response to elevated temperature through PIF4. Our results indicate that CRY1 signal by modulating PIF4 activity, and that multiple plant photoreceptors [CRY1 and PHYTOCHROME B (PHYB)] and ambient temperature can mediate morphological responses through the same signaling component-PIF4.

Fast Adjustments of the Asian Summer Monsoon to Anthropogenic Aerosols

NASA Astrophysics Data System (ADS)

Li, Xiaoqiong; Ting, Mingfang; Lee, Dong Eun

2018-01-01

Anthropogenic aerosols are a major factor contributing to human-induced climate change, particularly over the densely populated Asian monsoon region. Understanding the physical processes controlling the aerosol-induced changes in monsoon rainfall is essential for reducing the uncertainties in the future projections of the hydrological cycle. Here we use multiple coupled and atmospheric general circulation models to explore the physical mechanisms for the aerosol-driven monsoon changes on different time scales. We show that anthropogenic aerosols induce an overall reduction in monsoon rainfall and circulation, which can be largely explained by the fast adjustments over land north of 20∘N. This fast response occurs before changes in sea surface temperature (SST), largely driven by aerosol-cloud interactions. However, aerosol-induced SST feedbacks (slow response) cause substantial changes in the monsoon meridional circulation over the oceanic regions. Both the land-ocean asymmetry and meridional temperature gradient are key factors in determining the overall monsoon circulation response.

Beyond NK cells: the expanding universe of innate lymphoid cells.

PubMed

Cella, Marina; Miller, Hannah; Song, Christina

2014-01-01

For a long time, natural killer (NK) cells were thought to be the only innate immune lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different innate lymphoid cell (ILC) populations found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. These ILC populations closely mirror the phenotype of adaptive T helper subsets in their repertoire of secreted soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response that is appropriate for the incoming insult. Here, we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development.

Yersinia pestis and Yersinia pseudotuberculosis infection: a regulatory RNA perspective

PubMed Central

Martínez-Chavarría, Luary C.; Vadyvaloo, Viveka

2015-01-01

Yersinia pestis, responsible for causing fulminant plague, has evolved clonally from the enteric pathogen, Y. pseudotuberculosis, which in contrast, causes a relatively benign enteric illness. An ~97% nucleotide identity over 75% of their shared protein coding genes is maintained between these two pathogens, leaving much conjecture regarding the molecular determinants responsible for producing these vastly different disease etiologies, host preferences and transmission routes. One idea is that coordinated production of distinct factors required for host adaptation and virulence in response to specific environmental cues could contribute to the distinct pathogenicity distinguishing these two species. Small non-coding RNAs that direct posttranscriptional regulation have recently been identified as key molecules that may provide such timeous expression of appropriate disease enabling factors. Here the burgeoning field of small non-coding regulatory RNAs in Yersinia pathogenesis is reviewed from the viewpoint of adaptive colonization, virulence and divergent evolution of these pathogens. PMID:26441890

Basic helix-loop-helix transcription factors JASMONATE-ASSOCIATED MYC2-LIKE1 (JAM1), JAM2, and JAM3 are negative regulators of jasmonate responses in Arabidopsis.

PubMed

Sasaki-Sekimoto, Yuko; Jikumaru, Yusuke; Obayashi, Takeshi; Saito, Hikaru; Masuda, Shinji; Kamiya, Yuji; Ohta, Hiroyuki; Shirasu, Ken

2013-09-01

Jasmonates regulate transcriptional reprogramming during growth, development, and defense responses. Jasmonoyl-isoleucine, an amino acid conjugate of jasmonic acid (JA), is perceived by the protein complex composed of the F-box protein CORONATINE INSENSITIVE1 (COI1) and JASMONATE ZIM DOMAIN (JAZ) proteins, leading to the ubiquitin-dependent degradation of JAZ proteins. This activates basic helix-loop-helix-type MYC transcription factors to regulate JA-responsive genes. Here, we show that the expression of genes encoding other basic helix-loop-helix transcription factors, JASMONATE ASSOCIATED MYC2-LIKE1 (JAM1), JAM2, and JAM3, is positively regulated in a COI1- and MYC2-dependent manner in Arabidopsis (Arabidopsis thaliana). However, contrary to myc2, the jam1jam2jam3 triple mutant exhibited shorter roots when treated with methyl jasmonate (MJ), indicating enhanced responsiveness to JA. Our genome-wide expression analyses revealed that key jasmonate metabolic genes as well as a set of genes encoding transcription factors that regulate the JA-responsive metabolic genes are negatively regulated by JAMs after MJ treatment. Consistently, loss of JAM genes resulted in higher accumulation of anthocyanin in MJ-treated plants as well as higher accumulation of JA and 12-hydroxyjasmonic acid in wounded plants. These results show that JAMs negatively regulate the JA responses in a manner that is mostly antagonistic to MYC2.

Basic Helix-Loop-Helix Transcription Factors JASMONATE-ASSOCIATED MYC2-LIKE1 (JAM1), JAM2, and JAM3 Are Negative Regulators of Jasmonate Responses in Arabidopsis1[W][OPEN

PubMed Central

Sasaki-Sekimoto, Yuko; Jikumaru, Yusuke; Obayashi, Takeshi; Saito, Hikaru; Masuda, Shinji; Kamiya, Yuji; Ohta, Hiroyuki; Shirasu, Ken

2013-01-01

Jasmonates regulate transcriptional reprogramming during growth, development, and defense responses. Jasmonoyl-isoleucine, an amino acid conjugate of jasmonic acid (JA), is perceived by the protein complex composed of the F-box protein CORONATINE INSENSITIVE1 (COI1) and JASMONATE ZIM DOMAIN (JAZ) proteins, leading to the ubiquitin-dependent degradation of JAZ proteins. This activates basic helix-loop-helix-type MYC transcription factors to regulate JA-responsive genes. Here, we show that the expression of genes encoding other basic helix-loop-helix transcription factors, JASMONATE ASSOCIATED MYC2-LIKE1 (JAM1), JAM2, and JAM3, is positively regulated in a COI1- and MYC2-dependent manner in Arabidopsis (Arabidopsis thaliana). However, contrary to myc2, the jam1jam2jam3 triple mutant exhibited shorter roots when treated with methyl jasmonate (MJ), indicating enhanced responsiveness to JA. Our genome-wide expression analyses revealed that key jasmonate metabolic genes as well as a set of genes encoding transcription factors that regulate the JA-responsive metabolic genes are negatively regulated by JAMs after MJ treatment. Consistently, loss of JAM genes resulted in higher accumulation of anthocyanin in MJ-treated plants as well as higher accumulation of JA and 12-hydroxyjasmonic acid in wounded plants. These results show that JAMs negatively regulate the JA responses in a manner that is mostly antagonistic to MYC2. PMID:23852442

Perceived Partner Responsiveness Predicts Diurnal Cortisol Profiles 10 Years Later.

PubMed

Slatcher, Richard B; Selcuk, Emre; Ong, Anthony D

2015-07-01

Several decades of research have demonstrated that marital relationships have a powerful influence on physical health. However, surprisingly little is known about how marriage affects health--both in terms of psychological processes and biological ones. Over a 10-year period, we investigated the associations between perceived partner responsiveness--the extent to which people feel understood, cared for, and appreciated by their romantic partners--and diurnal cortisol in a large sample of married and cohabitating couples in the United States. Partner responsiveness predicted higher cortisol values at awakening and steeper (i.e., healthier) cortisol slopes at the 10-year follow-up. These associations remained strong after we controlled for demographic factors, depressive symptoms, agreeableness, and other positive and negative relationship factors. Furthermore, declines in negative affect over the 10-year period mediated the prospective association between responsiveness and cortisol slope. These findings suggest that diurnal cortisol may be a key biological pathway through which social relationships affect long-term health. © The Author(s) 2015.

Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity.

PubMed

Henis-Korenblit, Sivan; Zhang, Peichuan; Hansen, Malene; McCormick, Mark; Lee, Seung-Jae; Cary, Michael; Kenyon, Cynthia

2010-05-25

When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Factors promoting sustainability of education innovations: a comparison of faculty perceptions and existing frameworks.

PubMed

Loh, Lawrence C; Friedman, Stacey R; Burdick, William P

2013-01-01

Health professions education uses innovative projects to promote faculty development and institution change. Faculty perceptions of the factors that promote project sustainability affect how faculty conceptualize and implement their innovations, which influences whether and how they plan for sustainability. This paper compares educators' perceptions of factors that influence sustainability in innovative projects with factors identified in project sustainability literature, to identify areas of convergence and divergence. Using questionnaires, faculty development fellowship participants from Brazil and India shared their perceptions on factors influencing their project's sustainability. An analysis framework was developed from existing project sustainability literature; faculty responses were then coded through an iterative process. Key sustainability themes identified by faculty included project-level factors related to project design, stakeholder support, monitoring and evaluation, and project outcomes. Identified context level factors were related to institutional and governmental support as well as self-motivation and peer support. Availability of resources and funding were identified as relevant at both the project and context levels. Project-level factors were more often cited than context-level factors as key to ensuring sustainability. Faculty development efforts in health professions education should employ strategies to target these themes in promoting innovation sustainability. These include preengagement with institutional leaders, alignment with public sector goals, strategic diffusion of information, project expansion and transferability, capacity building in monitoring and evaluation, and creation of a community of educators for information exchange and support.

Concurrent schedules: Effects of time- and response-allocation constraints

PubMed Central

Davison, Michael

1991-01-01

Five pigeons were trained on concurrent variable-interval schedules arranged on two keys. In Part 1 of the experiment, the subjects responded under no constraints, and the ratios of reinforcers obtainable were varied over five levels. In Part 2, the conditions of the experiment were changed such that the time spent responding on the left key before a subsequent changeover to the right key determined the minimum time that must be spent responding on the right key before a changeover to the left key could occur. When the left key provided a higher reinforcer rate than the right key, this procedure ensured that the time allocated to the two keys was approximately equal. The data showed that such a time-allocation constraint only marginally constrained response allocation. In Part 3, the numbers of responses emitted on the left key before a changeover to the right key determined the minimum number of responses that had to be emitted on the right key before a changeover to the left key could occur. This response constraint completely constrained time allocation. These data are consistent with the view that response allocation is a fundamental process (and time allocation a derivative process), or that response and time allocation are independently controlled, in concurrent-schedule performance. PMID:16812632

Factors influencing consumer adoption of USB-based Personal Health Records in Taiwan

PubMed Central

2012-01-01

Background Usually patients receive healthcare services from multiple hospitals, and consequently their healthcare data are dispersed over many facilities’ paper and electronic-based record systems. Therefore, many countries have encouraged the research on data interoperability, access, and patient authorization. This study is an important part of a national project to build an information exchange environment for cross-hospital digital medical records carried out by the Department of Health (DOH) of Taiwan in May 2008. The key objective of the core project is to set up a portable data exchange environment in order to enable people to maintain and own their essential health information. This study is aimed at exploring the factors influencing behavior and adoption of USB-based Personal Health Records (PHR) in Taiwan. Methods Quota sampling was used, and structured questionnaires were distributed to the outpatient department at ten medical centers which participated in the DOH project to establish the information exchange environment across hospitals. A total of 3000 questionnaires were distributed and 1549 responses were collected, out of those 1465 were valid, accumulating the response rate to 48.83%. Results 1025 out of 1465 respondents had expressed their willingness to apply for the USB-PHR. Detailed analysis of the data reflected that there was a remarkable difference in the “usage intention” between the PHR adopters and non-adopters (χ2 =182.4, p < 0.001). From the result of multivariate logistic regression analyses, we found the key factors affecting patients’ adoption pattern were Usage Intention (OR, 9.43, 95%C.I., 5.87-15.16), Perceived Usefulness (OR, 1.60; 95%C.I., 1.11-2.29) and Subjective Norm (OR, 1.47; 95%C.I., 1.21-1.78). Conclusions Higher Usage Intentions, Perceived Usefulness and Subjective Norm of patients were found to be the key factors influencing PHR adoption. Thus, we suggest that government and hospitals should promote the potential usefulness of PHR, and physicians should encourage patients' to adopt the PHR. PMID:22925029

Differential Response to Soil Salinity in Endangered Key Tree Cactus: Implications for Survival in a Changing Climate

PubMed Central

Goodman, Joie; Maschinski, Joyce; Hughes, Phillip; McAuliffe, Joe; Roncal, Julissa; Powell, Devon; Sternberg, Leonel O'reilly

2012-01-01

Understanding reasons for biodiversity loss is essential for developing conservation and management strategies and is becoming increasingly urgent with climate change. Growing at elevations <1.4 m in the Florida Keys, USA, the endangered Key tree cactus (Pilosocereus robinii) experienced 84 percent loss of total stems from 1994 to 2007. The most severe losses of 99 and 88 percent stems occurred in the largest populations in the Lower Keys, where nine storms with high wind velocities and storm surges, occurred during this period. In contrast, three populations had substantial stem proliferation. To evaluate possible mortality factors related to changes in climate or forest structure, we examined habitat variables: soil salinity, elevation, canopy cover, and habitat structure near 16 dying or dead and 18 living plants growing in the Lower Keys. Soil salinity and elevation were the preliminary factors that discriminated live and dead plants. Soil salinity was 1.5 times greater, but elevation was 12 cm higher near dead plants than near live plants. However, distribution-wide stem loss was not significantly related to salinity or elevation. Controlled salinity trials indicated that salt tolerance to levels above 40 mM NaCl was related to maternal origin. Salt sensitive plants from the Lower Keys had less stem growth, lower root:shoot ratios, lower potassium: sodium ratios and lower recovery rate, but higher δ 13C than a salt tolerant lineage of unknown origin. Unraveling the genetic structure of salt tolerant and salt sensitive lineages in the Florida Keys will require further genetic tests. Worldwide rare species restricted to fragmented, low-elevation island habitats, with little or no connection to higher ground will face challenges from climate change-related factors. These great conservation challenges will require traditional conservation actions and possibly managed relocation that must be informed by studies such as these. PMID:22403670

Differential response to soil salinity in endangered key tree cactus: implications for survival in a changing climate.

PubMed

Goodman, Joie; Maschinski, Joyce; Hughes, Phillip; McAuliffe, Joe; Roncal, Julissa; Powell, Devon; Sternberg, Leonel O'reilly

2012-01-01

Understanding reasons for biodiversity loss is essential for developing conservation and management strategies and is becoming increasingly urgent with climate change. Growing at elevations <1.4 m in the Florida Keys, USA, the endangered Key tree cactus (Pilosocereus robinii) experienced 84 percent loss of total stems from 1994 to 2007. The most severe losses of 99 and 88 percent stems occurred in the largest populations in the Lower Keys, where nine storms with high wind velocities and storm surges, occurred during this period. In contrast, three populations had substantial stem proliferation. To evaluate possible mortality factors related to changes in climate or forest structure, we examined habitat variables: soil salinity, elevation, canopy cover, and habitat structure near 16 dying or dead and 18 living plants growing in the Lower Keys. Soil salinity and elevation were the preliminary factors that discriminated live and dead plants. Soil salinity was 1.5 times greater, but elevation was 12 cm higher near dead plants than near live plants. However, distribution-wide stem loss was not significantly related to salinity or elevation. Controlled salinity trials indicated that salt tolerance to levels above 40 mM NaCl was related to maternal origin. Salt sensitive plants from the Lower Keys had less stem growth, lower root:shoot ratios, lower potassium: sodium ratios and lower recovery rate, but higher δ (13)C than a salt tolerant lineage of unknown origin. Unraveling the genetic structure of salt tolerant and salt sensitive lineages in the Florida Keys will require further genetic tests. Worldwide rare species restricted to fragmented, low-elevation island habitats, with little or no connection to higher ground will face challenges from climate change-related factors. These great conservation challenges will require traditional conservation actions and possibly managed relocation that must be informed by studies such as these.

Bryophyte-cyanobacteria associations as regulators of the northern latitude carbon balance in response to global change.

PubMed

Lindo, Zoë; Nilsson, Marie-Charlotte; Gundale, Michael J

2013-07-01

Ecosystems in the far north, including arctic and boreal biomes, are a globally significant pool of carbon (C). Global change is proposed to influence both C uptake and release in these ecosystems, thereby potentially affecting whether they act as C sources or sinks. Bryophytes (i.e., mosses) serve a variety of key functions in these systems, including their association with nitrogen (N2 )-fixing cyanobacteria, as thermal insulators of the soil, and producers of recalcitrant litter, which have implications for both net primary productivity (NPP) and heterotrophic respiration. While ground-cover bryophytes typically make up a small proportion of the total biomass in northern systems, their combined physical structure and N2 -fixing capabilities facilitate a disproportionally large impact on key processes that control ecosystem C and N cycles. As such, the response of bryophyte-cyanobacteria associations to global change may influence whether and how ecosystem C balances are influenced by global change. Here, we review what is known about their occurrence and N2 -fixing activity, and how bryophyte systems will respond to several key global change factors. We explore the implications these responses may have in determining how global change influences C balances in high northern latitudes. © 2013 Blackwell Publishing Ltd.

Population attributable risk of key modifiable risk factors associated with non-exclusive breastfeeding in Nigeria.

PubMed

Ogbo, Felix Akpojene; Page, Andrew; Idoko, John; Agho, Kingsley E

2018-02-13

Non-exclusive breastfeeding (non-EBF) is a risk factor for many of the 2300 under-five deaths occurring daily in Nigeria - a developing country with approximately 40 million children. This study aimed to quantify and compare the attributable burden of key modifiable risk factors associated with non-EBF in Nigeria to inform strategic policy responses and initiatives. Relative risk and exposure prevalence for selected modifiable risk factors were used to calculate population attributable fractions based on Nigeria Demographic and Health Surveys data for the period (1999-2013). Scenarios based on feasible impact of community-based interventions in reducing exposure prevalence were also considered to calculate comparative potential impact fractions. In Nigeria, an estimated 22.8% (95% Confidence Interval, CI: 9.2-37.0%) of non-EBF was attributable to primary and no maternal education; 24.7% (95% CI: 9.5-39.5%) to middle and poor household wealth, 9.7% (1.7-18.1%) to lower number (1-3) and no antenatal care visits; 18.8% (95% CI: 6.9-30.8%) to home delivery and 16.6% (95% CI: 3.0-31.3%) to delivery assisted by a non-health professional. In combination, more than half of all cases of non-EBF (64.5%; 95% CI: 50.0-76.4%) could be attributed to those modifiable risk factors. Scenarios based on feasible impacts of community-based approaches to improve health service access and human capacity suggest that an avoidable burden of non-EBF practice of approximately 11% (95% CI: -5.4; 24.7) is achievable. Key modifiable risk factors contribute significantly to non-EBF in Nigerian women. Community-based initiatives and appropriate socio-economic government policies that specifically consider those modifiable risk factors could substantially reduce non-EBF practice in Nigeria.

Krüppel-like Factor 4 modulates interleukin-6 release in human dendritic cells after in vitro stimulation with Aspergillus fumigatus and Candida albicans.

PubMed

Czakai, Kristin; Leonhardt, Ines; Dix, Andreas; Bonin, Michael; Linde, Joerg; Einsele, Hermann; Kurzai, Oliver; Loeffler, Jürgen

2016-06-27

Invasive fungal infections are associated with high mortality rates and are mostly caused by the opportunistic fungi Aspergillus fumigatus and Candida albicans. Immune responses against these fungi are still not fully understood. Dendritic cells (DCs) are crucial players in initiating innate and adaptive immune responses against fungal infections. The immunomodulatory effects of fungi were compared to the bacterial stimulus LPS to determine key players in the immune response to fungal infections. A genome wide study of the gene regulation of human monocyte-derived dendritic cells (DCs) confronted with A. fumigatus, C. albicans or LPS was performed and Krüppel-like factor 4 (KLF4) was identified as the only transcription factor that was down-regulated in DCs by both fungi but induced by stimulation with LPS. Downstream analysis demonstrated the influence of KLF4 on the interleukine-6 expression in human DCs. Furthermore, KLF4 regulation was shown to be dependent on pattern recognition receptor ligation. Therefore KLF4 was identified as a controlling element in the IL-6 immune response with a unique expression pattern comparing fungal and LPS stimulation.

Photoemission stability of negative electron affinity GaN photocathode

NASA Astrophysics Data System (ADS)

Zhang, Junju; Wang, Xiaohui; Yang, Wenzheng; Tang, Weidong; Fu, Xiaoqian; Li, Biao; Chang, Benkang

2012-11-01

The stability for reflection-mode GaN photocathode has been investigated by monitoring the photocurrent and the spectral response at room temperature. We watch that the photocurrent of the cathode decays with time in the vacuum system, and compare the spectral response curves after activation and after degradation. The photocurrent decay mechanism for reflection-mode NEA GaN photocathode was studied by the surface model ?GaN (Mg) :Cs ?:O-Cs. The reduction of the effective dipole quantity, which is caused by harmful gases, is the key factor of the photocurrent reduction.

The APOA1/C3/A4/A5 cluster and markers of allostatic load in the Boston Puerto Rican Health Study

USDA-ARS?s Scientific Manuscript database

The APOA1/C3/A4/A5 cluster encodes key regulators of plasma lipids. Interactions between dietary factors and single nucleotide polymorphisms (SNPs) in the cluster have been reported. Allostatic load, or physiological dysregulation in response to stress, has been implicated in shaping health disparit...

Promoting a Culture of Integrity: A Study of Faculty and Student Perceptions of Academic Dishonesty at a Large Public Midwestern University

ERIC Educational Resources Information Center

Stevens, Tanisha N.

2012-01-01

Research reveals that reducing academic misconduct requires an understanding of factors that influence the two key stakeholders in the epidemic: students who engage in academically dishonest behaviors and faculty who are charged with the responsibility of reporting and deterring the behavior (e.g., Prenshaw, Straughan & Albers-Miller, 2000).…

An Exploration of the Alienation Experienced by African American Parents from Their Children's Educational Environment

ERIC Educational Resources Information Center

Brandon, Regina R.; Higgins, Kyle; Pierce, Tom; Tandy, Richard; Sileo, Nancy

2010-01-01

Current research suggests that parents are a key component to the school success of their children. However, in today's world, parents often work long hours, have more than one job, and participate in multiple responsibilities that may limit their participation. Because of the variety of factors that impinge on parents, educators often criticize…

Mlc is a transcriptional activator with a key role in integrating cyclic AMP receptor protein and integration host factor regulation of leukotoxin RNA synthesis in Aggregatibacter actinomycetemcomitans

USDA-ARS?s Scientific Manuscript database

Aggregatibacter actinomycetemcomitans, a periodontal pathogen, synthesizes leukotoxin (LtxA), a protein that helps the bacterium evade the host immune response. Transcription of the ltxA operon is induced during anaerobic growth. The cAMP receptor protein (CRP) indirectly increases ltxA expression...

Do Ethical Judgments Depend on the Type of Response Scale? Comparing Acceptability versus Unacceptability Judgments in the Case of Life-Ending Procedures

ERIC Educational Resources Information Center

Sastre, Maria Teresa Munoz; Gonzalez, Charlene; Lhermitte, Astrid; Sorum, Paul C.; Mullet, Etienne

2010-01-01

Using Functional Measurement (Anderson, 2008), Frileux, Lelievre, Munoz Sastre, Mullet, and Sorum (2003) examined the joint impact of several key factors on lay people's judgments of the acceptability of physicians' interventions to end patients' lives. The level of acceptability was high, and the information integration rule that best described…

Higher Education in Kenya: An Assessment of Current Responses to the Imperative of Widening Access

ERIC Educational Resources Information Center

Odhiambo, George

2016-01-01

Higher education is a key factor in a nation's effort to develop a highly skilled workforce for competing in the global economy. In this paper, current trends in accessibility, equity, participation and financing of higher education in Kenya are examined. The paper explores the challenges which need to be confronted and discusses the way forward…

Innate immune response to Burkholderia mallei.

PubMed

Saikh, Kamal U; Mott, Tiffany M

2017-06-01

Burkholderia mallei is a facultative intracellular pathogen that causes the highly contagious and often the fatal disease, glanders. With its high rate of infectivity via aerosol and recalcitrance toward antibiotics, this pathogen is considered a potential biological threat agent. This review focuses on the most recent literature highlighting host innate immune response to B. mallei. Recent studies focused on elucidating host innate immune responses to the novel mechanisms and virulence factors employed by B. mallei for survival. Studies suggest that pathogen proteins manipulate various cellular processes, including host ubiquitination pathways, phagosomal escape, and actin-cytoskeleton rearrangement. Immune-signaling molecules such as Toll-like receptors, nucleotode-binding oligomerization domain, myeloid differentiation primary response protein 88, and proinflammatory cytokines such as interferon-gamma and tumor necrosis factor-α, play key roles in the induction of innate immune responses. Modifications in B. mallei lipopolysaccharide, in particular, the lipid A acyl groups, stimulate immune responses via Toll-like receptor4 activation that may contribute to persistent infection. Mortality is high because of septicemia and immune pathogenesis with B. mallei exposure. An effective innate immune response is critical to controlling the acute phase of the infection. Both vaccination and therapeutic approaches are necessary for complete protection against B. mallei.

Osteoblast role in osteoarthritis pathogenesis.

PubMed

Maruotti, Nicola; Corrado, Addolorata; Cantatore, Francesco P

2017-11-01

Even if osteoarthritis pathogenesis is still poorly understood, numerous evidences suggest that osteoblasts dysregulation plays a key role in osteoarthritis pathogenesis. An abnormal expression of OPG and RANKL has been described in osteoarthritis osteoblasts, which is responsible for abnormal bone remodeling and decreased mineralization. Alterations in genes expression are involved in dysregulation of osteoblast function, bone remodeling, and mineralization, leading to osteoarthritis development. Moreover, osteoblasts produce numerous transcription factors, growth factors, and other proteic molecules which are involved in osteoarthritis pathogenesis. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

Changes in regulation of a transcription factor lead to autogamy in cultivated tomatoes.

PubMed

Chen, Kai-Yi; Cong, Bin; Wing, Rod; Vrebalov, Julia; Tanksley, Steven D

2007-10-26

We report the cloning of Style2.1, the major quantitative trait locus responsible for a key floral attribute (style length) associated with the evolution of self-pollination in cultivated tomatoes. The gene encodes a putative transcription factor that regulates cell elongation in developing styles. The transition from cross-pollination to self-pollination was accompanied, not by a change in the STYLE2.1 protein, but rather by a mutation in the Style2.1 promoter that results in a down-regulation of Style2.1 expression during flower development.

Publics and biobanks: Pan-European diversity and the challenge of responsible innovation.

PubMed

Gaskell, George; Gottweis, Herbert; Starkbaum, Johannes; Gerber, Monica M; Broerse, Jacqueline; Gottweis, Ursula; Hobbs, Abbi; Helén, Ilpo; Paschou, Maria; Snell, Karoliina; Soulier, Alexandra

2013-01-01

This article examines public perceptions of biobanks in Europe using a multi-method approach combining quantitative and qualitative data. It is shown that public support for biobanks in Europe is variable and dependent on a range of interconnected factors: people's engagement with biobanks; concerns about privacy and data security, and trust in the socio-political system, key actors and institutions involved in biobanks. We argue that the biobank community needs to acknowledge the impact of these factors if they are to successfully develop and integrate biobanks at a pan-European level.

Dis-integration of communication in healthcare education: Workplace learning challenges and opportunities.

PubMed

Rosenbaum, Marcy E

2017-11-01

The purpose of this paper, based on a 2016 Heidelberg International Conference on Communication in Healthcare (ICCH) plenary presentation, is to examine a key problem in communication skills training for health professional learners. Studies have pointed to a decline in medical students' communication skills and attitudes as they proceed through their education, particularly during their clinical workplace training experiences. This paper explores some of the key factors in this disintegration, drawing on selected literature and highlighting some curriculum efforts and research conducted at the University of Iowa Carver College of Medicine as a case study of these issues. Five key factors contributing to the disintegration of communication skills and attitudes are presented including: 1) lack of formal communication skills training during clinical clerkships; 2) informal workplace teaching failing to explicitly address learner clinical communication skills; 3) emphasizing content over process in relation to clinician-patient interactions; 4) the relationship between ideal communication models and the realities of clinical practice; and 5) clinical teachers' lack of knowledge and skills to effectively teach about communication in the clinical workplace. Within this discussion, potential practical responses by individual clinical teachers and broader curricular and faculty development efforts to address each of these factors are presented. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Investigations on response time of magnetorheological elastomer under compression mode

NASA Astrophysics Data System (ADS)

Zhu, Mi; Yu, Miao; Qi, Song; Fu, Jie

2018-05-01

For efficient fast control of vibration system with magnetorheological elastomer (MRE)-based smart device, the response time of MRE material is the key parameter which directly affects the control performance of the vibration system. For a step coil current excitation, this paper proposed a Maxwell behavior model with time constant λ to describe the normal force response of MRE, and the response time of MRE was extracted through the separation of coil response time. Besides, the transient responses of MRE under compression mode were experimentally investigated, and the effects of (i) applied current, (ii) particle distribution and (iii) compressive strain on the response time of MRE were addressed. The results revealed that the three factors can affect the response characteristic of MRE quite significantly. Besides the intrinsic importance for contributing to the response evaluation and effective design of MRE device, this study may conduce to the optimal design of controller for MRE control system.

THE ENDOTHELIUM IN SEPSIS

PubMed Central

Ince, Can; Mayeux, Philip R.; Nguyen, Trung; Gomez, Hernando; Kellum, John A.; Ospina-Tascón, Gustavo A.; Hernandez, Glenn; Murray, Patrick; De Backer, Daniel

2017-01-01

Sepsis affects practically all aspects of endothelial cell (EC) function and is thought to be the key factor in the progression from sepsis to organ failure. Endothelial functions affected by sepsis include vasoregulation, barrier function, inflammation, and hemostasis. These are among other mechanisms often mediated by glycocalyx shedding, such as abnormal nitric oxide metabolism, up-regulation of reactive oxygen species generation due to down-regulation of endothelial-associated antioxidant defenses, transcellular communication, proteases, exposure of adhesion molecules, and activation of tissue factor. This review covers current insight in EC-associated hemostatic responses to sepsis and the EC response to inflammation. The endothelial cell lining is highly heterogeneous between different organ systems and consequently also in its response to sepsis. In this context, we discuss the response of the endothelial cell lining to sepsis in the kidney, liver, and lung. Finally, we discuss evidence as to whether the EC response to sepsis is adaptive or maladaptive. This study is a result of an Acute Dialysis Quality Initiative XIV Sepsis Workgroup meeting held in Bogota, Columbia, between October 12 and 15, 2014. PMID:26871664

Molecular analysis of UAS(E), a cis element containing stress response elements responsible for ethanol induction of the KlADH4 gene of Kluyveromyces lactis.

PubMed

Mazzoni, C; Santori, F; Saliola, M; Falcone, C

2000-01-01

KlADH4 is a gene of Kluyveromyces lactis encoding a mitochondrial alcohol dehydrogenase activity, which is specifically induced by ethanol and insensitive to glucose repression. In this work, we report the molecular analysis of UAS(E), an element of the KlADH4 promoter which is essential for the induction of KlADH4 in the presence of ethanol. UAS(E) contains five stress response elements (STREs), which have been found in many genes of Saccharomyces cerevisiae involved in the response of cells to conditions of stress. Whereas KlADH4 is not responsive to stress conditions, the STREs present in UAS(E) seem to play a key role in the induction of the gene by ethanol, a situation that has not been observed in the related yeast S. cerevisiae. Gel retardation experiments showed that STREs in the KlADH4 promoter can bind factor(s) under non-inducing conditions. Moreover, we observed that the RAP1 binding site present in UAS(E) binds KlRap1p.

A Drought-Inducible Transcription Factor Delays Reproductive Timing in Rice.

PubMed

Zhang, Chunyu; Liu, Jun; Zhao, Tao; Gomez, Adam; Li, Cong; Yu, Chunsheng; Li, Hongyu; Lin, Jianzhong; Yang, Yuanzhu; Liu, Bin; Lin, Chentao

2016-05-01

The molecular mechanisms underlying photoperiod or temperature control of flowering time have been recently elucidated, but how plants regulate flowering time in response to other external factors, such as water availability, remains poorly understood. Using a large-scale Hybrid Transcription Factor approach, we identified a bZIP transcriptional factor, O. sativa ABA responsive element binding factor 1 (OsABF1), which acts as a suppressor of floral transition in a photoperiod-independent manner. Simultaneous knockdown of both OsABF1 and its closest homologous gene, OsbZIP40, in rice (Oryza sativa) by RNA interference results in a significantly earlier flowering phenotype. Molecular and genetic analyses demonstrate that a drought regime enhances expression of the OsABF1 gene, which indirectly suppresses expression of the Early heading date 1 (Ehd1) gene that encodes a key activator of rice flowering. Furthermore, we identified a drought-inducible gene named OsWRKY104 that is under the direct regulation of OsABF1 Overexpression of OsWRKY104 can suppress Ehd1 expression and confers a later flowering phenotype in rice. Together, these findings reveal a novel pathway by which rice modulates heading date in response to the change of ambient water availability. © 2016 American Society of Plant Biologists. All Rights Reserved.

PITX1, a specificity determinant in the HIF-1α-mediated transcriptional response to hypoxia

PubMed Central

Mudie, Sharon; Bandarra, Daniel; Batie, Michael; Biddlestone, John; Moniz, Sonia; Ortmann, Brian; Shmakova, Alena; Rocha, Sonia

2014-01-01

Hypoxia is an important developmental cue for multicellular organisms but it is also a contributing factor for several human pathologies, such as stroke, cardiovascular diseases and cancer. In cells, hypoxia activates a major transcriptional program coordinated by the Hypoxia Inducible Factor (HIF) family. HIF can activate more than one hundred targets but not all of them are activated at the same time, and there is considerable cell type variability. In this report we identified the paired-like homeodomain pituitary transcription factor (PITX1), as a transcription factor that helps promote specificity in HIF-1α dependent target gene activation. Mechanistically, PITX1 associates with HIF-1β and it is important for the induction of certain HIF-1 dependent genes but not all. In particular, PITX1 controls the HIF-1α-dependent expression of the histone demethylases; JMJD2B, JMJD2A, JMJD2C and JMJD1B. Functionally, PITX1 is required for the survival and proliferation responses in hypoxia, as PITX1 depleted cells have higher levels of apoptotic markers and reduced proliferation. Overall, our study identified PITX1 as a key specificity factor in HIF-1α dependent responses, suggesting PITX1 as a protein to target in hypoxic cancers. PMID:25558831

Mycorrhizal fungal establishment in agricultural soils: factors determining inoculation success.

PubMed

Verbruggen, Erik; van der Heijden, Marcel G A; Rillig, Matthias C; Kiers, E Toby

2013-03-01

Soil biota provide a number of key ecological services to natural and agricultural ecosystems. Increasingly, inoculation of soils with beneficial soil biota is being considered as a tool to enhance plant productivity and sustainability of agricultural ecosystems. However, one important bottleneck is the establishment of viable microbial populations that can persist over multiple seasons. Here, we explore the factors responsible for establishment of the beneficial soil fungi, arbuscular mycorrhizal fungi (AMF), which can enhance the yield of a wide range of agricultural crops. We evaluate field application potential and discuss ecological and evolutionary factors responsible for application success. We identify three factors that determine inoculation success and AM fungal persistence in soils: species compatibility (can the introduced species thrive under the imposed circumstances?); field carrying capacity (the habitat niche available to AMF); and priority effects (the influence of timing and competition on the establishment of alternative stable communities). We explore how these factors can be employed for establishment and persistence of AMF. We address the importance of inoculum choice, plant choice, management practices and timing of inoculation for the successful manipulation of the resulting AMF community.

Factors influencing antibiotic prescribing habits and use of sensitivity testing amongst veterinarians in Europe.

PubMed

De Briyne, N; Atkinson, J; Pokludová, L; Borriello, S P; Price, S

2013-11-16

The Heads of Medicines Agencies and the Federation of Veterinarians of Europe undertook a survey to gain a better insight into the decision-making process of veterinarians in Europe when deciding which antibiotics to prescribe. The survey was completed by 3004 practitioners from 25 European countries. Analysis was to the level of different types of practitioner (food producing (FP) animals, companion animals, equines) and country for Belgium, Czech Republic, France, Germany, Spain, Sweden and the UK. Responses indicate no single information source is universally considered critical, though training, published literature and experience were the most important. Factors recorded which most strongly influenced prescribing behaviour were sensitivity tests, own experience, the risk for antibiotic resistance developing and ease of administration. Most practitioners usually take into account responsible use warnings. Antibiotic sensitivity testing is usually performed where a treatment failure has occurred. Significant differences were observed in the frequency of sensitivity testing at the level of types of practitioners and country. The responses indicate a need to improve sensitivity tests and services, with the availability of rapid and cheaper testing being key factors.

Fork head controls the timing and tissue selectivity of steroid-induced developmental cell death

PubMed Central

Cao, Chike; Liu, Yanling; Lehmann, Michael

2007-01-01

Cell death during Drosophila melanogaster metamorphosis is controlled by the steroid hormone 20-hydroxyecdysone (20E). Elements of the signaling pathway that triggers death are known, but it is not known why some tissues, and not others, die in response to a particular hormone pulse. We found that loss of the tissue-specific transcription factor Fork head (Fkh) is both required and sufficient to specify a death response to 20E in the larval salivary glands. Loss of fkh itself is a steroid-controlled event that is mediated by the 20E-induced BR-C gene, and that renders the key death regulators hid and reaper hormone responsive. These results implicate the D. melanogaster FOXA orthologue Fkh with a novel function as a competence factor for steroid-controlled cell death. They explain how a specific tissue is singled out for death, and why this tissue survives earlier hormone pulses. More generally, they suggest that cell identity factors like Fkh play a pivotal role in the normal control of developmental cell death. PMID:17339378

Factors influencing antibiotic prescribing habits and use of sensitivity testing amongst veterinarians in Europe

PubMed Central

De Briyne, N.; Atkinson, J.; Pokludová, L.; Borriello, S. P.; Price, S.

2013-01-01

The Heads of Medicines Agencies and the Federation of Veterinarians of Europe undertook a survey to gain a better insight into the decision-making process of veterinarians in Europe when deciding which antibiotics to prescribe. The survey was completed by 3004 practitioners from 25 European countries. Analysis was to the level of different types of practitioner (food producing (FP) animals, companion animals, equines) and country for Belgium, Czech Republic, France, Germany, Spain, Sweden and the UK. Responses indicate no single information source is universally considered critical, though training, published literature and experience were the most important. Factors recorded which most strongly influenced prescribing behaviour were sensitivity tests, own experience, the risk for antibiotic resistance developing and ease of administration. Most practitioners usually take into account responsible use warnings. Antibiotic sensitivity testing is usually performed where a treatment failure has occurred. Significant differences were observed in the frequency of sensitivity testing at the level of types of practitioners and country. The responses indicate a need to improve sensitivity tests and services, with the availability of rapid and cheaper testing being key factors. PMID:24068699

Drought response in wheat: key genes and regulatory mechanisms controlling root system architecture and transpiration efficiency

NASA Astrophysics Data System (ADS)

Kulkarni, Manoj; Soolanayakanahally, Raju; Ogawa, Satoshi; Uga, Yusaku; Selvaraj, Michael G.; Kagale, Sateesh

2017-12-01

Abiotic stresses such as drought, heat, salinity and flooding threaten global food security. Crop genetic improvement with increased resilience to abiotic stresses is a critical component of crop breeding strategies. Wheat is an important cereal crop and a staple food source globally. Enhanced drought tolerance in wheat is critical for sustainable food production and global food security. Recent advances in drought tolerance research have uncovered many key genes and transcription regulators governing morpho-physiological traits. Genes controlling root architecture and stomatal development play an important role in soil moisture extraction and its retention, and therefore have been targets of molecular breeding strategies for improving drought tolerance. In this systematic review, we have summarized evidence of beneficial contributions of root and stomatal traits to plant adaptation to drought stress. Specifically, we discuss a few key genes such as DRO1 in rice and ERECTA in Arabidopsis and rice that were identified to be the enhancers of drought tolerance via regulation of root traits and transpiration efficiency. Additionally, we highlight several transcription factor families, such as ERF (ethylene response factors), DREB (dehydration responsive element binding), ZFP (zinc finger proteins), WRKY and MYB that were identified to be both positive and negative regulators of drought responses in wheat, rice, maize and/or Arabidopsis. The overall aim of this review was to provide an overview of candidate genes that have been tested as regulators of drought response in plants. The lack of a reference genome sequence for wheat and nontransgenic approaches for manipulation of gene functions in the past had impeded high-resolution interrogation of functional elements, including genes and QTLs, and their application in cultivar improvement. The recent developments in wheat genomics and reverse genetics, including the availability of a gold-standard reference genome sequence and advent genome editing technologies, are expected to aid in deciphering of the functional roles of genes and regulatory networks underlying adaptive phenological traits, and utilizing the outcomes of such studies in developing drought tolerance cultivars.

Drought Response in Wheat: Key Genes and Regulatory Mechanisms Controlling Root System Architecture and Transpiration Efficiency.

PubMed

Kulkarni, Manoj; Soolanayakanahally, Raju; Ogawa, Satoshi; Uga, Yusaku; Selvaraj, Michael G; Kagale, Sateesh

2017-01-01

Abiotic stresses such as, drought, heat, salinity, and flooding threaten global food security. Crop genetic improvement with increased resilience to abiotic stresses is a critical component of crop breeding strategies. Wheat is an important cereal crop and a staple food source globally. Enhanced drought tolerance in wheat is critical for sustainable food production and global food security. Recent advances in drought tolerance research have uncovered many key genes and transcription regulators governing morpho-physiological traits. Genes controlling root architecture and stomatal development play an important role in soil moisture extraction and its retention, and therefore have been targets of molecular breeding strategies for improving drought tolerance. In this systematic review, we have summarized evidence of beneficial contributions of root and stomatal traits to plant adaptation to drought stress. Specifically, we discuss a few key genes such as, DRO1 in rice and ERECTA in Arabidopsis and rice that were identified to be the enhancers of drought tolerance via regulation of root traits and transpiration efficiency. Additionally, we highlight several transcription factor families, such as, ERF (ethylene response factors), DREB (dehydration responsive element binding), ZFP (zinc finger proteins), WRKY, and MYB that were identified to be both positive and negative regulators of drought responses in wheat, rice, maize, and/or Arabidopsis. The overall aim of this review is to provide an overview of candidate genes that have been identified as regulators of drought response in plants. The lack of a reference genome sequence for wheat and non-transgenic approaches for manipulation of gene functions in wheat in the past had impeded high-resolution interrogation of functional elements, including genes and QTLs, and their application in cultivar improvement. The recent developments in wheat genomics and reverse genetics, including the availability of a gold-standard reference genome sequence and advent of genome editing technologies, are expected to aid in deciphering of the functional roles of genes and regulatory networks underlying adaptive phenological traits, and utilizing the outcomes of such studies in developing drought tolerant cultivars.

Analysing workplace violence towards health care staff in public hospitals using alternative ordered response models: the case of north-eastern Turkey.

PubMed

Çelik, Ali Kemal; Oktay, Erkan; Çebi, Kübranur

2017-09-01

The main objective of this article is to determine key factors that may have a significant effect on the verbal abuse, emotional abuse and physical assault of health care workers in north-eastern Turkey. A self-administered survey was completed by 450 health care workers in three well-established hospitals in Erzurum, Turkey. Because of the discrete and ordered nature of the dependent variable of the survey, the data were analysed using four distinctive ordered response models. Results revealed that several key variables were found to be a significant determinant of workplace violence, such as the type of health institution, occupational position, weekly working hours, weekly shift hours, number of daily patient contacts, age group of the respondents, experience in the health sector, training against workplace violence and current policies of the hospitals and the Turkish Ministry of Health.

Earth Observing System/Meteorological Satellite (EOS/METSAT). Advanced Microwave Sounding Unit-A (AMSU-A) Contamination Control Plan

NASA Technical Reports Server (NTRS)

Fay, M.

1998-01-01

This Contamination Control Plan is submitted in response the Contract Document requirements List (CDRL) 007 under contract NAS5-32314 for the Earth Observing System (EOS) Advanced Microwave Sounding Unit A (AMSU-A). In response to the CDRL instructions, this document defines the level of cleanliness and methods/procedures to be followed to achieve adequate cleanliness/contamination control, and defines the required approach to maintain cleanliness/contamination control through shipping, observatory integration, test, and flight. This plan is also applicable to the Meteorological Satellite (METSAT) except where requirements are identified as EOS-specific. This plan is based on two key factors: a. The EOS/METSAT AMSU-A Instruments are not highly contamination sensitive. b. Potential contamination of other EOS Instruments is a key concern as addressed in Section 9/0 of the Performance Assurance Requirements for EOS/METSAT Integrated Programs AMSU-A Instrument (MR) (NASA Specification S-480-79).

Identification of the key ecological factors influencing vegetation degradation in semi-arid agro-pastoral ecotone considering spatial scales

NASA Astrophysics Data System (ADS)

Peng, Yu; Wang, Qinghui; Fan, Min

2017-11-01

When assessing re-vegetation project performance and optimizing land management, identification of the key ecological factors inducing vegetation degradation has crucial implications. Rainfall, temperature, elevation, slope, aspect, land use type, and human disturbance are ecological factors affecting the status of vegetation index. However, at different spatial scales, the key factors may vary. Using Helin County, Inner-Mongolia, China as the study site and combining remote sensing image interpretation, field surveying, and mathematical methods, this study assesses key ecological factors affecting vegetation degradation under different spatial scales in a semi-arid agro-pastoral ecotone. It indicates that the key factors are different at various spatial scales. Elevation, rainfall, and temperature are identified as crucial for all spatial extents. Elevation, rainfall and human disturbance are key factors for small-scale quadrats of 300 m × 300 m and 600 m × 600 m, temperature and land use type are key factors for a medium-scale quadrat of 1 km × 1 km, and rainfall, temperature, and land use are key factors for large-scale quadrats of 2 km × 2 km and 5 km × 5 km. For this region, human disturbance is not the key factor for vegetation degradation across spatial scales. It is necessary to consider spatial scale for the identification of key factors determining vegetation characteristics. The eco-restoration programs at various spatial scales should identify key influencing factors according their scales so as to take effective measurements. The new understanding obtained in this study may help to explore the forces which driving vegetation degradation in the degraded regions in the world.

Skeletal muscle hypertrophy and regeneration: interplay between the myogenic regulatory factors (MRFs) and insulin-like growth factors (IGFs) pathways.

PubMed

Zanou, Nadège; Gailly, Philippe

2013-11-01

Adult skeletal muscle can regenerate in response to muscle damage. This ability is conferred by the presence of myogenic stem cells called satellite cells. In response to stimuli such as injury or exercise, these cells become activated and express myogenic regulatory factors (MRFs), i.e., transcription factors of the myogenic lineage including Myf5, MyoD, myogenin, and Mrf4 to proliferate and differentiate into myofibers. The MRF family of proteins controls the transcription of important muscle-specific proteins such as myosin heavy chain and muscle creatine kinase. Different growth factors are secreted during muscle repair among which insulin-like growth factors (IGFs) are the only ones that promote both muscle cell proliferation and differentiation and that play a key role in muscle regeneration and hypertrophy. Different isoforms of IGFs are expressed during muscle repair: IGF-IEa, IGF-IEb, or IGF-IEc (also known as mechano growth factor, MGF) and IGF-II. MGF is expressed first and is observed in satellite cells and in proliferating myoblasts whereas IGF-Ia and IGF-II expression occurs at the state of muscle fiber formation. Interestingly, several studies report the induction of MRFs in response to IGFs stimulation. Inversely, IGFs expression may also be regulated by MRFs. Various mechanisms are proposed to support these interactions. In this review, we describe the general process of muscle hypertrophy and regeneration and decipher the interactions between the two groups of factors involved in the process.

Serology in the 21st Century: The Molecular-Level Analysis of the Serum Antibody Repertoire

PubMed Central

Wine, Yariv; Horton, Andrew P.; Ippolito, Gregory C.; Georgiou, George

2015-01-01

The ensemble of antibodies found in serum and secretions represents the key adaptive component of B-cell mediated humoral immunity. The antibody repertoire is shaped by the historical record of exposure to exogenous factors such as pathogens and vaccines, as well as by endogenous host-intrinsic factors such as genetics, self-antigens, and age. Thanks to very recent technology advancements it is now becoming possible to identify and quantify the individual antibodies comprising the serological repertoire. In parallel, the advent of high throughput methods for antigen and immunosignature discovery opens up unprecedented opportunities to transform our understanding of numerous key questions in adaptive humoral immunity, including the nature and dynamics of serological memory, the role of polyspecific antibodies in health and disease and how protective responses to infections or vaccine challenge arise. Additionally, these technologies also hold great promise for therapeutic antibody and biomarker discovery in a variety of settings PMID:26172290

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection

PubMed Central

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments. PMID:28928987

Key Aroma Compounds in Smoked Cooked Loin.

PubMed

Kosowska, Monika; Majcher, Małgorzata A; Jeleń, Henryk H; Fortuna, Teresa

2018-04-11

Smoked cooked loin is one of the most popular meat products in Poland. In this study, key volatile compounds in this traditional Polish meat product were determined using gas chromatography-olfactometry and aroma extract dilution analysis (AEDA). In total, 27 odor-active volatile compounds were identified, with flavor dilution (FD) factors ranging from 4 to 1024, with the highest FD factors noted for 2-methoxyphenol, 2-methoxy-4-(prop-2-enyl)phenol, and 2-methoxy-4-( E)-(prop-1-en-1-yl)phenol. Results of the quantitative analyses based on determinations with stable isotope dilution assays (SIDAs) and standard addition (SA), followed by calculations of the odor activity value (OAV), enabled identifying 24 of the volatile compounds responsible for flavor development in the analyzed smoked cooked loin. The highest OAVs were obtained for 2-methoxyphenol, 2-methyl-3-furanthiol, 1-octen-3-one, and 2-methyl-3-(methyldithio)furan.

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection.

PubMed

Phillips, Cristy

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments.

Traumatic Brain Injury as a Risk Factor for Alzheimer's Disease: Is Inflammatory Signaling a Key Player?

PubMed

Djordjevic, Jelena; Sabbir, Mohammad Golam; Albensi, Benedict C

2016-01-01

Traumatic brain injury (TBI) has become a significant medical and social concern within the last 30 years. TBI has acute devastating effects, and in many cases, seems to initiate long-term neurodegeneration. With advances in medical technology, many people are now surviving severe brain injuries and their long term consequences. Post trauma effects include communication problems, sensory deficits, emotional and behavioral problems, physical complications and pain, increased suicide risk, dementia, and an increased risk for chronic CNS diseases, such as Alzheimer's disease (AD). In this review, we provide an introduction to TBI and hypothesize how it may lead to neurodegenerative disease in general and AD in particular. In addition, we discuss the evidence that supports the hypothesis that TBI may lead to AD. In particular, we focus on inflammatory responses as key processes in TBI-induced secondary injury, with emphasis on nuclear factor kappa B (NF-κB) signaling.

Mitochondrial and Chloroplast Stress Responses Are Modulated in Distinct Touch and Chemical Inhibition Phases1[OPEN

PubMed Central

Ivanova, Aneta; Millar, A. Harvey; Whelan, James

2016-01-01

Previous studies have identified a range of transcription factors that modulate retrograde regulation of mitochondrial and chloroplast functions in Arabidopsis (Arabidopsis thaliana). However, the relative importance of these regulators and whether they act downstream of separate or overlapping signaling cascades is still unclear. Here, we demonstrate that multiple stress-related signaling pathways, with distinct kinetic signatures, converge on overlapping gene sets involved in energy organelle function. The transcription factor ANAC017 is almost solely responsible for transcript induction of marker genes around 3 to 6 h after chemical inhibition of organelle function and is a key regulator of mitochondrial and specific types of chloroplast retrograde signaling. However, an independent and highly transient gene expression phase, initiated within 10 to 30 min after treatment, also targets energy organelle functions, and is related to touch and wounding responses. Metabolite analysis demonstrates that this early response is concurrent with rapid changes in tricarboxylic acid cycle intermediates and large changes in transcript abundance of genes encoding mitochondrial dicarboxylate carrier proteins. It was further demonstrated that transcription factors AtWRKY15 and AtWRKY40 have repressive regulatory roles in this touch-responsive gene expression. Together, our results show that several regulatory systems can independently affect energy organelle function in response to stress, providing different means to exert operational control. PMID:27208304

49 CFR 1.13 - OST Key Responsibilities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 false OST Key Responsibilities. 1.13 Section 1.13... of the Secretary § 1.13 OST Key Responsibilities. (a) The OST is responsible for: (1) Providing... Government; (5) Encouraging maximum private development of transportation services; (6) Providing responsive...

49 CFR 1.13 - OST Key Responsibilities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 1 2012-10-01 2012-10-01 false OST Key Responsibilities. 1.13 Section 1.13... of the Secretary § 1.13 OST Key Responsibilities. (a) The OST is responsible for: (1) Providing... Government; (5) Encouraging maximum private development of transportation services; (6) Providing responsive...

49 CFR 1.13 - OST Key Responsibilities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 1 2014-10-01 2014-10-01 false OST Key Responsibilities. 1.13 Section 1.13... of the Secretary § 1.13 OST Key Responsibilities. (a) The OST is responsible for: (1) Providing... Government; (5) Encouraging maximum private development of transportation services; (6) Providing responsive...

Ambient temperature signalling in plants.

PubMed

Wigge, Philip A

2013-10-01

Plants are exposed to daily and seasonal fluctuations in temperature. Within the 'ambient' temperature range (about 12-27°C for Arabidopsis) temperature differences have large effects on plant growth and development, disease resistance pathways and the circadian clock without activating temperature stress pathways. It is this developmental sensing and response to non-stressful temperatures that will be covered in this review. Recent advances have revealed key players in mediating temperature signals. The bHLH transcription factor PHYTOCHROME INTERACTING FACTOR4 (PIF4) has been shown to be a hub for multiple responses to warmer temperature in Arabidopsis, including flowering and hypocotyl elongation. Changes in chromatin state are involved in transmitting temperature signals to the transcriptome. Determining the precise mechanisms of temperature perception represents an exciting goal for the field. Copyright © 2013 Elsevier Ltd. All rights reserved.

Alternative Splicing Control of Abiotic Stress Responses.

PubMed

Laloum, Tom; Martín, Guiomar; Duque, Paula

2018-02-01

Alternative splicing, which generates multiple transcripts from the same gene, is an important modulator of gene expression that can increase proteome diversity and regulate mRNA levels. In plants, this post-transcriptional mechanism is markedly induced in response to environmental stress, and recent studies have identified alternative splicing events that allow rapid adjustment of the abundance and function of key stress-response components. In agreement, plant mutants defective in splicing factors are severely impaired in their response to abiotic stress. Notably, mounting evidence indicates that alternative splicing regulates stress responses largely by targeting the abscisic acid (ABA) pathway. We review here current understanding of post-transcriptional control of plant stress tolerance via alternative splicing and discuss research challenges for the near future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Socially disempowered women as the key to addressing change in Malawi: how do they do it?

PubMed

Macintyre, Linda M; Rankin, Sally; Pinderhughes, Howard; Waters, Catherine M; Schell, Ellen; Fiedler, Rachel

2013-01-01

Malawi women are in the ironic juxtaposition of being socially disempowered while, at the same time, thought to hold the key to shaping an effective community response to the HIV crisis. Based on this juxtaposition, a descriptive, qualitative study was conducted in Malawi and the United States where 26 participants from nongovernmental organizations (NGOs) and community-based organizations (CBOs) discussed the roles of Malawi women. Interviews were audiotaped, transcribed, and analyzed. We identified an improvement in women's economic status as the strongest factor in reducing gender inequities. Through providing stipends for rural Malawi women, one NGO created unintended changes in gender roles.

Computer based imaging and analysis of root gravitropism

NASA Technical Reports Server (NTRS)

Evans, M. L.; Ishikawa, H.

1997-01-01

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

[Incentivising personal responsibility: conceptual clarification and evidence].

PubMed

Schmidt, Harald

2012-01-01

Two meanings of personal responsibility are distinguished, and different policy options for promoting health and responsibility are presented. Key insights from research seeking to promote personal responsibility through health information and incentives are outlined and discussed with regard to their potential to improve health and reduce cost. Data is presented on the socioeconomic characteristics of incentive programme users. It is concluded that due to different factors the availability of data regarding the effectiveness of incentive programmes is unsatisfactory. Evaluation requirements set out in the German Social Security Code (SGB V) should focus not only on cost, but should also extend to changes in health status and the socioeconomic status of users: provisions should be revised accordingly. Copyright © 2012. Published by Elsevier GmbH.

The adaptive radiation of lichen-forming Teloschistaceae is associated with sunscreening pigments and a bark-to-rock substrate shift

PubMed Central

Gaya, Ester; Fernández-Brime, Samantha; Vargas, Reinaldo; Lachlan, Robert F.; Gueidan, Cécile; Ramírez-Mejía, Martín; Lutzoni, François

2015-01-01

Adaptive radiations play key roles in the generation of biodiversity and biological novelty, and therefore understanding the factors that drive them remains one of the most important challenges of evolutionary biology. Although both intrinsic innovations and extrinsic ecological opportunities contribute to diversification bursts, few studies have looked at the synergistic effect of such factors. Here we investigate the Teloschistales (Ascomycota), a group of >1,000 lichenized species with variation in species richness and phenotypic traits that hinted at a potential adaptive radiation. We found evidence for a dramatic increase in diversification rate for one of four families within this order—Teloschistaceae—which occurred ∼100 Mya (Late Cretaceous) and was associated with a switch from bark to rock and from shady to sun-exposed habitats. This adaptation to sunny habitats is likely to have been enabled by a contemporaneous key novel phenotypic innovation: the production in both vegetative structure (thallus) and fruiting body (apothecia) of anthraquinones, secondary metabolites known to protect against UV light. We found that the two ecological factors (sun exposure and rock substrate) and the phenotypic innovation (anthraquinones in the thallus) were all significant when testing for state-dependent shifts in diversification rates, and together they seem likely to be responsible for the success of the Teloschistaceae, one of the largest lichen-forming fungal lineages. Our results support the idea that adaptive radiations are driven not by a single factor or key innovation, but require a serendipitous combination of both intrinsic biotic and extrinsic abiotic and ecological factors. PMID:26324894

The adaptive radiation of lichen-forming Teloschistaceae is associated with sunscreening pigments and a bark-to-rock substrate shift.

PubMed

Gaya, Ester; Fernández-Brime, Samantha; Vargas, Reinaldo; Lachlan, Robert F; Gueidan, Cécile; Ramírez-Mejía, Martín; Lutzoni, François

2015-09-15

Adaptive radiations play key roles in the generation of biodiversity and biological novelty, and therefore understanding the factors that drive them remains one of the most important challenges of evolutionary biology. Although both intrinsic innovations and extrinsic ecological opportunities contribute to diversification bursts, few studies have looked at the synergistic effect of such factors. Here we investigate the Teloschistales (Ascomycota), a group of >1,000 lichenized species with variation in species richness and phenotypic traits that hinted at a potential adaptive radiation. We found evidence for a dramatic increase in diversification rate for one of four families within this order--Teloschistaceae--which occurred ∼ 100 Mya (Late Cretaceous) and was associated with a switch from bark to rock and from shady to sun-exposed habitats. This adaptation to sunny habitats is likely to have been enabled by a contemporaneous key novel phenotypic innovation: the production in both vegetative structure (thallus) and fruiting body (apothecia) of anthraquinones, secondary metabolites known to protect against UV light. We found that the two ecological factors (sun exposure and rock substrate) and the phenotypic innovation (anthraquinones in the thallus) were all significant when testing for state-dependent shifts in diversification rates, and together they seem likely to be responsible for the success of the Teloschistaceae, one of the largest lichen-forming fungal lineages. Our results support the idea that adaptive radiations are driven not by a single factor or key innovation, but require a serendipitous combination of both intrinsic biotic and extrinsic abiotic and ecological factors.

On the relationship between response selection and response inhibition: An individual differences approach.

PubMed

Bender, Angela D; Filmer, Hannah L; Garner, K G; Naughtin, Claire K; Dux, Paul E

2016-11-01

The abilities to select appropriate responses and suppress unwanted actions are key executive functions that enable flexible and goal-directed behavior. However, to date it has been unclear whether these two cognitive operations tap a common action control resource or reflect two distinct processes. In the present study, we used an individual differences approach to examine the underlying relationships across seven paradigms that varied in their response selection and response inhibition requirements: stop-signal, go-no-go, Stroop, flanker, single-response selection, psychological refractory period, and attentional blink tasks. A confirmatory factor analysis suggested that response inhibition and response selection are separable, with stop-signal and go-no-go task performance being related to response inhibition, and performance in the psychological refractory period, Stroop, single-response selection, and attentional blink tasks being related to response selection. These findings provide evidence in support of the hypothesis that response selection and response inhibition reflect two distinct cognitive operations.

Salt-Sensitive Hypertension: Perspectives on Intrarenal Mechanisms

PubMed Central

Majid, Dewan S.A.; Prieto, Minolfa C.; Navar, L Gabriel

2015-01-01

Salt sensitive hypertension is characterized by increases in blood pressure in response to increases in dietary salt intake and is associated with an enhanced risk of cardiovascular and renal morbidity. Although researchers have sought for decades to understand how salt sensitivity develops in humans, the mechanisms responsible for the increases in blood pressure in response to high salt intake are complex and only partially understood. Until now, scientists have been unable to explain why some individuals are salt sensitive and others are salt resistant. Although a central role for the kidneys in the development of salt sensitivity and hypertension has been generally accepted, it is also recognized that hypertension is of multifactorial origin and a variety of factors can induce, or prevent, blood pressure responsiveness to the manipulation of salt intake. Excess salt intake in susceptible persons may also induce inappropriate central and sympathetic nervous system responses and increase the production of intrarenal angiotensin II, catecholamines and other factors such as oxidative stress and inflammatory cytokines. One key factor is the concomitant inappropriate or paradoxical activation of the intrarenal renin-angiotensin system, by high salt intake. This is reflected by the increases in urinary angiotensinogen during high salt intake in salt sensitive models. A complex interaction between neuroendocrine factors and the kidney may underlie the propensity for some individuals to retain salt and develop salt-dependent hypertension. In this review, we focus mainly on the renal contributions that provide the mechanistic link between chronic salt intake and the development of hypertension. PMID:26028244

Characterization of StABF1, a stress-responsive bZIP transcription factor from Solanum tuberosum L. that is phosphorylated by StCDPK2 in vitro.

PubMed

Muñiz García, María Noelia; Giammaria, Verónica; Grandellis, Carolina; Téllez-Iñón, María Teresa; Ulloa, Rita María; Capiati, Daniela Andrea

2012-04-01

ABF/AREB bZIP transcription factors mediate plant abiotic stress responses by regulating the expression of stress-related genes. These proteins bind to the abscisic acid (ABA)-responsive element (ABRE), which is the major cis-acting regulatory sequence in ABA-dependent gene expression. In an effort to understand the molecular mechanisms of abiotic stress resistance in cultivated potato (Solanum tuberosum L.), we have cloned and characterized an ABF/AREB-like transcription factor from potato, named StABF1. The predicted protein shares 45-57% identity with A. thaliana ABFs proteins and 96% identity with the S. lycopersicum SlAREB1 and presents all of the distinctive features of ABF/AREB transcription factors. Furthermore, StABF1 is able to bind to the ABRE in vitro. StABF1 gene is induced in response to ABA, drought, salt stress and cold, suggesting that it might be a key regulator of ABA-dependent stress signaling pathways in cultivated potato. StABF1 is phosphorylated in response to ABA and salt stress in a calcium-dependent manner, and we have identified a potato CDPK isoform (StCDPK2) that phosphorylates StABF1 in vitro. Interestingly, StABF1 expression is increased during tuber development and by tuber-inducing conditions (high sucrose/nitrogen ratio) in leaves. We also found that StABF1 calcium-dependent phosphorylation is stimulated by tuber-inducing conditions and inhibited by gibberellic acid, which inhibits tuberization.

Post-translational regulation of WRKY transcription factors in plant immunity.

PubMed

Ishihama, Nobuaki; Yoshioka, Hirofumi

2012-08-01

Plants have evolved immune system to protect themselves against invading pathogens. Recent research has illustrated that signaling networks, after perception of diverse pathogen-derived signals, facilitate transcriptional reprogramming through mitogen-activated protein kinase (MAPK) cascades. WRKY proteins, which comprise a large family of plant transcription factors, are key players in plant immune responses. WRKY transcription factors participate in the control of defense-related genes either as positive or as negative regulators, and essentially are regulated at the transcriptional level. Emerging evidence emphasizes that group I WRKY transcription factors, which contain a conserved motif in the N-terminal region, are also activated by MAPK-dependent phosphorylation, underlining their importance in plant immunity. Copyright © 2012 Elsevier Ltd. All rights reserved.

iTRAQ-Based Quantitative Proteomic Comparison of Early- and Late-Passage Human Dermal Papilla Cell Secretome in Relation to Inducing Hair Follicle Regeneration.

PubMed

Zhang, Huan; Zhu, Ning-Xia; Huang, Keng; Cai, Bo-Zhi; Zeng, Yang; Xu, Yan-Ming; Liu, Yang; Yuan, Yan-Ping; Lin, Chang-Min

2016-01-01

Alopecia is an exceedingly prevalent problem that lacks effective therapy. Recently, research has focused on early-passage dermal papilla cells (DPCs), which have hair inducing activity both in vivo and in vitro. Our previous study indicated that factors secreted from early-passage DPCs contribute to hair follicle (HF) regeneration. To identify which factors are responsible for HF regeneration and why late-passage DPCs lose this potential, we collected 48-h-culture medium (CM) from both of passage 3 and 9 DPCs, and subcutaneously injected the DPC-CM into NU/NU mice. Passage 3 DPC-CM induced HF regeneration, based on the emergence of a white hair coat, but passage 9 DPC-CM did not. In order to identify the key factors responsible for hair induction, CM from passage 3 and 9 DPCs was analyzed by iTRAQ-based quantitative proteomic technology. We identified 1360 proteins, of which 213 proteins were differentially expressed between CM from early-passage vs. late-passage DPCs, including SDF1, MMP3, biglycan and LTBP1. Further analysis indicated that the differentially-expressed proteins regulated the Wnt, TGF-β and BMP signaling pathways, which directly and indirectly participate in HF morphogenesis and regeneration. Subsequently, we selected 19 proteins for further verification by multiple reaction monitoring (MRM) between the two types of CM. These results indicate DPC-secreted proteins play important roles in HF regeneration, with SDF1, MMP3, biglycan, and LTBP1 being potential key inductive factors secreted by dermal papilla cells in the regeneration of hair follicles.

SnRK1-triggered switch of bZIP63 dimerization mediates the low-energy response in plants

PubMed Central

Mair, Andrea; Pedrotti, Lorenzo; Wurzinger, Bernhard; Anrather, Dorothea; Simeunovic, Andrea; Weiste, Christoph; Valerio, Concetta; Dietrich, Katrin; Kirchler, Tobias; Nägele, Thomas; Vicente Carbajosa, Jesús; Hanson, Johannes; Baena-González, Elena; Chaban, Christina; Weckwerth, Wolfram; Dröge-Laser, Wolfgang; Teige, Markus

2015-01-01

Metabolic adjustment to changing environmental conditions, particularly balancing of growth and defense responses, is crucial for all organisms to survive. The evolutionary conserved AMPK/Snf1/SnRK1 kinases are well-known metabolic master regulators in the low-energy response in animals, yeast and plants. They act at two different levels: by modulating the activity of key metabolic enzymes, and by massive transcriptional reprogramming. While the first part is well established, the latter function is only partially understood in animals and not at all in plants. Here we identified the Arabidopsis transcription factor bZIP63 as key regulator of the starvation response and direct target of the SnRK1 kinase. Phosphorylation of bZIP63 by SnRK1 changed its dimerization preference, thereby affecting target gene expression and ultimately primary metabolism. A bzip63 knock-out mutant exhibited starvation-related phenotypes, which could be functionally complemented by wild type bZIP63, but not by a version harboring point mutations in the identified SnRK1 target sites. DOI: http://dx.doi.org/10.7554/eLife.05828.001 PMID:26263501

Investigation of Stimulation-Response Relationships for Complex Fracture Systems in Enhanced Geothermal Reservoirs

DOE Data Explorer

Fu, Pengcheng; Johnson, Scott M.; Carrigan, Charles R.

2011-01-01

Hydraulic fracturing is currently the primary method for stimulating low-permeability geothermal reservoirs and creating Enhanced (or Engineered) Geothermal Systems (EGS) with improved permeability and heat production efficiency. Complex natural fracture systems usually exist in the formations to be stimulated and it is therefore critical to understand the interactions between existing fractures and newly created fractures before optimal stimulation strategies can be developed. Our study aims to improve the understanding of EGS stimulation-response relationships by developing and applying computer-based models that can effectively reflect the key mechanisms governing interactions between complex existing fracture networks and newly created hydraulic fractures. In this paper, we first briefly describe the key modules of our methodology, namely a geomechanics solver, a discrete fracture flow solver, a rock joint response model, an adaptive remeshing module, and most importantly their effective coupling. After verifying the numerical model against classical closed-form solutions, we investigate responses of reservoirs with different preexisting natural fractures to a variety of stimulation strategies. The factors investigated include: the in situ stress states (orientation of the principal stresses and the degree of stress anisotropy), pumping pressure, and stimulation sequences of multiple wells.

Role of interferon regulatory factor-1 in lipopolysaccharide-induced mitochondrial damage and oxidative stress responses in macrophages

PubMed Central

Deng, Song-Yun; Zhang, Le-Meng; Ai, Yu-hang; Pan, Pin-Hua; Zhao, Shuang-Ping; Su, Xiao-Li; Wu, Dong-Dong; Tan, Hong-Yi; Zhang, Li-Na; Tsung, Allan

2017-01-01

Sepsis causes many early deaths; both macrophage mitochondrial damage and oxidative stress responses are key factors in its pathogenesis. Although the exact mechanisms responsible for sepsis-induced mitochondrial damage are unknown, the nuclear transcription factor, interferon regulatory factor-1 (IRF-1) has been reported to cause mitochondrial damage in several diseases. Previously, we reported that in addition to promoting systemic inflammation, IRF-1 promoted the apoptosis of and inhibited autophagy in macrophages. In the present study, we hypothesized that lipopolysaccharide (LPS)-induced IRF-1 activation in macrophages may promote mitochondrial damage and oxidative stress. In vitro, LPS was found to promote IRF-1 activation, reactive oxygen species (ROS) production, adenosine triphosphate (ATP) depletion, superoxide dismutase (SOD) consumption, malondialdehyde (MDA) accumulation and mitochondrial depolarization in macrophages in a time- and dose-dependent manner. These effects were abrogated in cells in which IRF-1 was knocked down. Furthermore, IRF-1 overexpression increased LPS-induced oxidative stress responses and mitochondrial damage. In vivo, peritoneal macrophages obtained from IRF-1 knockout (KO) mice produced less ROS and had less mitochondrial depolarization and damage following the administration of LPS, when compared to their wild-type (WT) counterparts. In addition, IRF-1 KO mice exhibited a decreased release of mitochondrial DNA (mtDNA) following the administration of LPS. Thus, IRF-1 may be a critical factor in augmenting LPS-induced oxidative stress and mitochondrial damage in macrophages. PMID:28849179

Subset of heat-shock transcription factors required for the early response of Arabidopsis to excess light

PubMed Central

Jung, Hou-Sung; Crisp, Peter A.; Estavillo, Gonzalo M.; Cole, Benjamin; Hong, Fangxin; Mockler, Todd C.; Pogson, Barry J.; Chory, Joanne

2013-01-01

Sunlight provides energy for photosynthesis and is essential for nearly all life on earth. However, too much or too little light or rapidly fluctuating light conditions cause stress to plants. Rapid changes in the amount of light are perceived as a change in the reduced/oxidized (redox) state of photosynthetic electron transport components in chloroplasts. However, how this generates a signal that is relayed to changes in nuclear gene expression is not well understood. We modified redox state in the reference plant, Arabidopsis thaliana, using either excess light or low light plus the herbicide DBMIB (2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone), a well-known inhibitor of photosynthetic electron transport. Modification of redox state caused a change in expression of a common set of about 750 genes, many of which are known stress-responsive genes. Among the most highly enriched promoter elements in the induced gene set were heat-shock elements (HSEs), known motifs that change gene expression in response to high temperature in many systems. We show that HSEs from the promoter of the ASCORBATE PEROXIDASE 2 (APX2) gene were necessary and sufficient for APX2 expression in conditions of excess light, or under low light plus the herbicide. We tested APX2 expression phenotypes in overexpression and loss-of-function mutants of 15 Arabidopsis A-type heat-shock transcription factors (HSFs), and identified HSFA1D, HSFA2, and HSFA3 as key factors regulating APX2 expression in diverse stress conditions. Excess light regulates both the subcellular location of HSFA1D and its biochemical properties, making it a key early component of the excess light stress network of plants. PMID:23918368

Approaches to English Literacy Teaching in the Central Pacific Republic of Kiribati: Quality Teaching, Educational Aid and Curriculum Reform

ERIC Educational Resources Information Center

Burnett, Greg

2013-01-01

English literacy competence in the Central Pacific Republic of Kiribati is considered important for employment, overseas study and general engagement with a globalizing world. It is also considered as a key factor in the current government's response to climate change and sea level rise, enabling skilled relocation of I-Kiribati to other countries…

Epigenetic Regulation of Myeloid Cells

PubMed Central

IVASHKIV, LIONEL B.; PARK, SUNG HO

2017-01-01

Epigenetic regulation in myeloid cells is crucial for cell differentiation and activation in response to developmental and environmental cues. Epigenetic control involves posttranslational modification of DNA or chromatin, and is also coupled to upstream signaling pathways and transcription factors. In this review, we summarize key epigenetic events and how dynamics in the epigenetic landscape of myeloid cells shape the development, immune activation, and innate immune memory. PMID:27337441

Student Affairs Administrators & Well-Being: Examining Time in Field, Position Level and Factors That Have the Strongest Relationship to Well-Being

ERIC Educational Resources Information Center

Chessman, Hollie M.

2015-01-01

The voice of higher education student affairs professionals is under-represented in the well-being literature even though these campus community members are responsible for providing key programs and services that facilitate the holistic development of students. In order to understand the role of well-being in the work-life of these professionals,…

Autoshaping and automaintenance of a key-press response in squirrel monkeys

PubMed Central

Gamzu, Elkan; Schwam, Elias

1974-01-01

Following exposure for a minimum of 500 to 600 trials, three of four naive squirrel monkeys eventually pressed a response key, illumination of which always preceded delivery of a food pellet. Three other naive monkeys did not press the key when the pellets were delivered randomly with respect to key illumination. Despite some similarities to autoshaping using pigeons, the data indicate many points of difference when squirrel monkeys are used as subjects. Although key-food pairings were shown to be important in the acquisition of the key-press response, they were ineffective in maintaining the response when either a negative response-reinforcer dependency was introduced, or when there was no scheduled response-reinforcer dependency (fixed trial). Not all demonstrations of autoshaping can be considered to be under the control of those processes that are primarily responsible for the phenomena obtained in pigeons. PMID:16811749

Autoshaping and automaintenance of a key-press response in squirrel monkeys.

PubMed

Gamzu, E; Schwam, E

1974-03-01

Following exposure for a minimum of 500 to 600 trials, three of four naive squirrel monkeys eventually pressed a response key, illumination of which always preceded delivery of a food pellet. Three other naive monkeys did not press the key when the pellets were delivered randomly with respect to key illumination. Despite some similarities to autoshaping using pigeons, the data indicate many points of difference when squirrel monkeys are used as subjects. Although key-food pairings were shown to be important in the acquisition of the key-press response, they were ineffective in maintaining the response when either a negative response-reinforcer dependency was introduced, or when there was no scheduled response-reinforcer dependency (fixed trial). Not all demonstrations of autoshaping can be considered to be under the control of those processes that are primarily responsible for the phenomena obtained in pigeons.

Adipose-derived stem cells seeded in Pluronic F-127 hydrogel promotes diabetic wound healing.

PubMed

Kaisang, Lin; Siyu, Wang; Lijun, Fan; Daoyan, Pan; Xian, Cory J; Jie, Shen

2017-09-01

Chronic nonhealing wound is a multifactorial complication of diabetes that results specifically as a consequence of impaired angiogenesis and currently lacks in effective treatments. Although a stem cell-based therapy may provide a novel treatment to augment diabetic wound healing, inferior cell survival at the diabetic skin wound is one of the key causes that are responsible for the low efficacy of the stem cell therapy. In this work, we used an injectable, biocompatible, and thermosensitive hydrogel Pluronic F-127 to encapsulate allogeneic nondiabetic adipose-derived stem cells (ADSCs) and topically applied the cells to a full-thickness cutaneous wound in the streptozotocin-induced diabetic model in rats. The cells seeded in the hydrogel enhanced angiogenesis (CD31 marker) and promoted the cell proliferation (Ki67 marker) at the wound site and significantly accelerated wound closure, which was accompanied by facilitated regeneration of granulation tissue. Consistently, levels of the messenger RNA expression of key angiogenesis growth factor, vascular endothelial growth factor, and key wound healing growth factor, transforming growth factor beta 1, were also upregulated in the cell-treated wounds when compared with untreated wounds. The results indicated that the transplantation of allogeneic ADSCs via the hydrogel improves the efficiency of cell delivery and optimizes the performance of ADSCs for augmenting diabetic wound healing. In conclusion, this ADSC-based therapy may provide a novel therapeutic strategy for the treatment of nonhealing diabetic foot ulcers. Copyright © 2017 Elsevier Inc. All rights reserved.

Genome-wide expression analysis of soybean NF-Y genes reveals potential function in development and drought response.

PubMed

Quach, Truyen N; Nguyen, Hanh T M; Valliyodan, Babu; Joshi, Trupti; Xu, Dong; Nguyen, Henry T

2015-06-01

Nuclear factor-Y (NF-Y), a heterotrimeric transcription factor, is composed of NF-YA, NF-YB and NF-YC proteins. In plants, there are usually more than 10 genes for each family and their members have been identified to be key regulators in many developmental and physiological processes controlling gametogenesis, embryogenesis, nodule development, seed development, abscisic acid (ABA) signaling, flowering time, primary root elongation, blue light responses, endoplasmic reticulum (ER) stress response and drought tolerance. Taking the advantages of the recent soybean genome draft and information on functional characterizations of nuclear factor Y (NF-Y) transcription factor family in plants, we identified 21 GmNF-YA, 32 GmNF-YB, and 15 GmNF-YC genes in the soybean (Glycine max) genome. Phylogenetic analyses show that soybean's proteins share strong homology to Arabidopsis and many of them are closely related to functionally characterized NF-Y in plants. Expression analysis in various tissues of flower, leaf, root, seeds of different developmental stages, root hairs under rhizobium inoculation, and drought-treated roots and leaves revealed that certain groups of soybean NF-Y are likely involved in specific developmental and stress responses. This study provides extensive evaluation of the soybean NF-Y family and is particularly useful for further functional characterization of GmNF-Y proteins in seed development, nodulation and drought adaptation of soybean.

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.

Reporting for Duty During Mass Casualty Events: A Survey of Factors Influencing Emergency Medicine Physicians

PubMed Central

Snipes, Carly; Miramonti, Charles; Chisholm, Carey; Chisholm, Robin

2013-01-01

Background Academic medical centers play a major role in disaster response, and residents frequently serve as key resources in these situations. Studies examining health care professionals' willingness to report for duty in mass casualty situations have varying response rates, and studies of emergency medicine (EM) residents' willingness to report for duty in disaster events and factors that affect these responses are lacking. Objective We sought to determine EM resident and faculty willingness to report for duty during 4 disaster scenarios (natural, explosive, nuclear, and communicable), to identify factors that affect willingness to work, and to assess opinions regarding disciplinary action for physicians unwilling to work in a disaster situation. Methods We surveyed residents and faculty at 7 US teaching institutions with accredited EM residency programs between April and November 2010. Results A total of 229 faculty and 259 residents responded (overall response rate, 75.4%). Willingness to report for duty ranged from 54.1% for faculty in a natural disaster to 94.2% for residents in a nonnuclear explosive disaster. The 3 most important factors influencing disaster response were concern for the safety of the family, belief in the physician's duty to provide care, and availability of protective equipment. Faculty and residents recommended minimal or no disciplinary action for individuals unwilling to work, except in the infectious disease scenario. Conclusions Most EM residents and faculty indicated they would report for duty. Residents and faculty responses were similar in all but 1 scenario. Disciplinary action for individuals unwilling to work generally was not recommended. PMID:24404305

Response surface methodology investigation into the interactions between arsenic and humic acid in water during the coagulation process.

PubMed

Watson, Malcolm Alexander; Tubić, Aleksandra; Agbaba, Jasmina; Nikić, Jasmina; Maletić, Snežana; Molnar Jazić, Jelena; Dalmacija, Božo

2016-07-15

Interactions between arsenic and natural organic matter (NOM) are key limiting factors during the optimisation of drinking water treatment when significant amounts of both must be removed. This work uses Response Surface Methodology (RSM) to investigate how they interact during their simultaneous removal by iron chloride coagulation, using humic acid (HA) as a model NOM substance. Using a three factor Box-Behnken experimental design, As and HA removals were modelled, as well as a combined removal response. ANOVA results showed the significance of the coagulant dose for all three responses. At high initial arsenic concentrations (200μg/l), As removal was significantly hindered by the presence of HA. In contrast, the HA removal response was found to be largely independent of the initial As concentration, with the optimum coagulant dose increasing at increasing HA concentrations. The combined response was similar to the HA removal response, and the interactions evident are most interesting in terms of optimising treatment processes during the preparation of drinking water, highlighting the importance of utilizing RSM for such investigations. The combined response model was successfully validated with two different groundwaters used for drinking water supply in the Republic of Serbia, showing excellent agreement under similar experimental conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection

PubMed Central

Sun, Xingmin; Hirota, Simon A.

2014-01-01

Clostridium difficile (C. difficile) is the most common cause of nosocomial antibiotic-associated diarrhea and the etiologic agent of pseudomembranous colitis. The clinical manifestation of Clostridium difficile infection (CDI) is highly variable, from asymptomatic carriage, to mild self-limiting diarrhea, to the more severe pseudomembranous colitis. Furthermore, in extreme cases, colonic inflammation and tissue damage can lead to toxic megacolon, a condition requiring surgical intervention. C. difficile expresses two key virulence factors; the exotoxins, toxin A (TcdA) and toxin B (TcdB), which are glucosyltransferases that target host-cell monomeric GTPases. In addition, some hypervirulent strains produce a third toxin, binary toxin or C. difficile transferase (CDT), which may contribute to the pathogenesis of CDI. More recently, other factors such as surface layer proteins (SLPs) and flagellin have also been linked to the inflammatory responses observed in CDI. Although the adaptive immune response can influence the severity of CDI, the innate immune responses to C. difficile and its toxins play crucial roles in CDI onset, progression, and overall prognosis. Despite this, the innate immune responses in CDI have drawn relatively little attention from clinical researchers. Targeting these responses may prove useful clinically as adjuvant therapies, especially in refractory and/or recurrent CDI. This review will focus on recent advances in our understanding of how C. difficile and its toxins modulate innate immune responses that contribute to CDI pathogenesis. PMID:25242213

Soybean Roots Grown under Heat Stress Show Global Changes in Their Transcriptional and Proteomic Profiles

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

Valdés-López, Oswaldo; Batek, Josef; Gomez-Hernandez, Nicolas

2016-04-25

Heat stress is likely to be a key factor in the negative impact of climate change on crop production. Roots provide support, water and nutrients to other plant organs. Likewise, roots play an important role in the establishment of symbiotic associations with different microorganisms. Despite the physiological relevance of roots, few studies have examined the response of these plant organs to heat stress. In this study, we performed genome-wide transcriptomic and proteomic analyses on isolated root hairs, which are a single, epidermal cell type, and compared their response to whole roots. We identified 2,013 genes differentially regulated in root hairsmore » in response to heat stress. Our gene regulatory module analysis identified ten, key modules that controlled the majority of the transcriptional response to heat stress. We also conducted proteomic analysis on membrane fractions isolated from roots and root hairs. These experiments identified a variety of proteins whose expression changed within 3 hours of application of heat stress. Most of these proteins were predicted to play a role in thermotolerance, as well as in chromatin remodeling and post-transcriptional regulation. The data presented represent an in-depth analysis of the heat stress response of a single cell type in soybean.« less

Integrative analysis of DNA methylation and gene expression data identifies EPAS1 as a key regulator of COPD.

PubMed

Yoo, Seungyeul; Takikawa, Sachiko; Geraghty, Patrick; Argmann, Carmen; Campbell, Joshua; Lin, Luan; Huang, Tao; Tu, Zhidong; Foronjy, Robert F; Feronjy, Robert; Spira, Avrum; Schadt, Eric E; Powell, Charles A; Zhu, Jun

2015-01-01

Chronic Obstructive Pulmonary Disease (COPD) is a complex disease. Genetic, epigenetic, and environmental factors are known to contribute to COPD risk and disease progression. Therefore we developed a systematic approach to identify key regulators of COPD that integrates genome-wide DNA methylation, gene expression, and phenotype data in lung tissue from COPD and control samples. Our integrative analysis identified 126 key regulators of COPD. We identified EPAS1 as the only key regulator whose downstream genes significantly overlapped with multiple genes sets associated with COPD disease severity. EPAS1 is distinct in comparison with other key regulators in terms of methylation profile and downstream target genes. Genes predicted to be regulated by EPAS1 were enriched for biological processes including signaling, cell communications, and system development. We confirmed that EPAS1 protein levels are lower in human COPD lung tissue compared to non-disease controls and that Epas1 gene expression is reduced in mice chronically exposed to cigarette smoke. As EPAS1 downstream genes were significantly enriched for hypoxia responsive genes in endothelial cells, we tested EPAS1 function in human endothelial cells. EPAS1 knockdown by siRNA in endothelial cells impacted genes that significantly overlapped with EPAS1 downstream genes in lung tissue including hypoxia responsive genes, and genes associated with emphysema severity. Our first integrative analysis of genome-wide DNA methylation and gene expression profiles illustrates that not only does DNA methylation play a 'causal' role in the molecular pathophysiology of COPD, but it can be leveraged to directly identify novel key mediators of this pathophysiology.

The trypanocidal benznidazole promotes adaptive response to oxidative injury: Involvement of the nuclear factor-erythroid 2-related factor-2 (Nrf2) and multidrug resistance associated protein 2 (MRP2)

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

Rigalli, Juan Pablo

Oxidative stress is a frequent cause underlying drug-induced hepatotoxicity. Benznidazole (BZL) is the only trypanocidal agent available for treatment of Chagas disease in endemic areas. Its use is associated with side effects, including increases in biomarkers of hepatotoxicity. However, BZL potential to cause oxidative stress has been poorly investigated. Here, we evaluated the effect of a pharmacologically relevant BZL concentration (200 μM) at different time points on redox status and the counteracting mechanisms in the human hepatic cell line HepG2. BZL increased reactive oxygen species (ROS) after 1 and 3 h of exposure, returning to normality at 24 h. Additionally,more » BZL increased glutathione peroxidase activity at 12 h and the oxidized glutathione/total glutathione (GSSG/GSSG + GSH) ratio that reached a peak at 24 h. Thus, an enhanced detoxification of peroxide and GSSG formation could account for ROS normalization. GSSG/GSSG + GSH returned to control values at 48 h. Expression of the multidrug resistance-associated protein 2 (MRP2) and GSSG efflux via MRP2 were induced by BZL at 24 and 48 h, explaining normalization of GSSG/GSSG + GSH. BZL activated the nuclear erythroid 2-related factor 2 (Nrf2), already shown to modulate MRP2 expression in response to oxidative stress. Nrf2 participation was confirmed using Nrf2-knockout mice in which MRP2 mRNA expression was not affected by BZL. In summary, we demonstrated a ROS increase by BZL in HepG2 cells and a glutathione peroxidase- and MRP2 driven counteracting mechanism, being Nrf2 a key modulator of this response. Our results could explain hepatic alterations associated with BZL therapy. - Highlights: • BZL triggers a redox imbalance in the human hepatic cell line HepG2. • Concomitantly BZL triggers compensatory mechanisms to alleviate the redox injury. • Response mechanisms comprise an enhanced glutathione peroxidase and MRP2 activity. • Transcription factor Nrf2 plays a key role orchestrating compensatory mechanisms.« less

Specific association of mouse MDC1/NFBD1 with NBS1 at sites of DNA-damage.

PubMed

Lee, Alicia C; Fernandez-Capetillo, Oscar; Pisupati, Venkat; Jackson, Stephen P; Nussenzweig, André

2005-01-01

Human MDC1/NFBD1 has been found to interact with key players of the DNA-damage response machinery. Here, we identify and describe a functional homologue of MDC1/ NFBD1 in Mus musculus. The mouse homologue, mMDC1, retains the key motifs identified in the human protein and in response to ionizing radiation forms foci that co-localize with the MRE11-RAD50-NBS1 (MRN) complex and factors such as gammaH2AX and 53BP1. In addition, mMDC1 is associated with DNA damage sites generated during meiotic recombination as well as the X and Y chromosomes during the late stages of meiotic prophase I. Finally, whereas MDC1 shows strong colocalization with the MRN complex in response to DNA damage it does not co-localize with the MRN complex on replicating chromatin. These data suggest that mMDC1 is a marker for both exogenously and endogenously generated DNA double-stranded breaks and that its interaction with the MRN complex is initiated exclusively by DNA damage.

Pharmacy students in private institutions of higher education: motivating factors when studying pharmacy and influences on university choice.

PubMed

Loo, Jason S E; Lim, Shiao Wei; Ng, Yew Keong; Tiong, John J L

2017-12-01

To identify factors influencing the decisions of Malaysian first-year pharmacy undergraduate students in private higher education when choosing to pursue a degree in pharmacy as well as their choice of private university. This cross-sectional study employed a validated, self-administered questionnaire which was administered to 543 first-year pharmacy students from nine different private universities. Factor analysis was utilised to extract key factors from the responses. Descriptive and inferential statistics were used to analyse the data. Eight factors motivating students' decision to study pharmacy emerged from the responses, accounting for 63.8% of the variance observed. Students were primarily motivated by intrinsic interests, with work conditions and profession attributes also exerting significant influence. In terms of choice of private university, nine factors were identified, accounting for 73.8% of the variance observed. The image of the school and university were most influential factors in this context, followed by university safety, programme attributes and financial factors. First-year pharmacy students in the private higher education sector are motivated by intrinsic interest when choosing to study pharmacy over other courses, while their choice of private university is influenced primarily by the image of the school and university. © 2017 Royal Pharmaceutical Society.

Modeling the response of native steelhead to hatchery supplementation programs in an Idaho River

USGS Publications Warehouse

Byrne, Alan; Bjornn, T.C.; McIntyre, J.D.

1993-01-01

A life history model was used to predict the response of native steelhead Oncorhynchus mykiss in the Lochsa River, Idaho, to long-term supplementation with hatchery fry and smolts. The four key factors affecting the response of the native fish to a stocking program were (1) the number of native spawners, (2) the number of stocked fish, (3) the number and fitness of progeny from stocked fish, and (4) the amount of mating between hatchery and native fish. Long-term stocking of fry or smolts led to the extinction of native fish in some scenarios. The model can be used to help assess the risks and benefits of proposed stocking programs.

Mechanisms and Model Diversity of Trade-Wind Shallow Cumulus Cloud Feedbacks: A Review.

PubMed

Vial, Jessica; Bony, Sandrine; Stevens, Bjorn; Vogel, Raphaela

2017-01-01

Shallow cumulus clouds in the trade-wind regions are at the heart of the long standing uncertainty in climate sensitivity estimates. In current climate models, cloud feedbacks are strongly influenced by cloud-base cloud amount in the trades. Therefore, understanding the key factors controlling cloudiness near cloud-base in shallow convective regimes has emerged as an important topic of investigation. We review physical understanding of these key controlling factors and discuss the value of the different approaches that have been developed so far, based on global and high-resolution model experimentations and process-oriented analyses across a range of models and for observations. The trade-wind cloud feedbacks appear to depend on two important aspects: (1) how cloudiness near cloud-base is controlled by the local interplay between turbulent, convective and radiative processes; (2) how these processes interact with their surrounding environment and are influenced by mesoscale organization. Our synthesis of studies that have explored these aspects suggests that the large diversity of model responses is related to fundamental differences in how the processes controlling trade cumulus operate in models, notably, whether they are parameterized or resolved. In models with parameterized convection, cloudiness near cloud-base is very sensitive to the vigor of convective mixing in response to changes in environmental conditions. This is in contrast with results from high-resolution models, which suggest that cloudiness near cloud-base is nearly invariant with warming and independent of large-scale environmental changes. Uncertainties are difficult to narrow using current observations, as the trade cumulus variability and its relation to large-scale environmental factors strongly depend on the time and/or spatial scales at which the mechanisms are evaluated. New opportunities for testing physical understanding of the factors controlling shallow cumulus cloud responses using observations and high-resolution modeling on large domains are discussed.

Mechanisms and Model Diversity of Trade-Wind Shallow Cumulus Cloud Feedbacks: A Review

NASA Astrophysics Data System (ADS)

Vial, Jessica; Bony, Sandrine; Stevens, Bjorn; Vogel, Raphaela

2017-11-01

Shallow cumulus clouds in the trade-wind regions are at the heart of the long standing uncertainty in climate sensitivity estimates. In current climate models, cloud feedbacks are strongly influenced by cloud-base cloud amount in the trades. Therefore, understanding the key factors controlling cloudiness near cloud-base in shallow convective regimes has emerged as an important topic of investigation. We review physical understanding of these key controlling factors and discuss the value of the different approaches that have been developed so far, based on global and high-resolution model experimentations and process-oriented analyses across a range of models and for observations. The trade-wind cloud feedbacks appear to depend on two important aspects: (1) how cloudiness near cloud-base is controlled by the local interplay between turbulent, convective and radiative processes; (2) how these processes interact with their surrounding environment and are influenced by mesoscale organization. Our synthesis of studies that have explored these aspects suggests that the large diversity of model responses is related to fundamental differences in how the processes controlling trade cumulus operate in models, notably, whether they are parameterized or resolved. In models with parameterized convection, cloudiness near cloud-base is very sensitive to the vigor of convective mixing in response to changes in environmental conditions. This is in contrast with results from high-resolution models, which suggest that cloudiness near cloud-base is nearly invariant with warming and independent of large-scale environmental changes. Uncertainties are difficult to narrow using current observations, as the trade cumulus variability and its relation to large-scale environmental factors strongly depend on the time and/or spatial scales at which the mechanisms are evaluated. New opportunities for testing physical understanding of the factors controlling shallow cumulus cloud responses using observations and high-resolution modeling on large domains are discussed.

Mechanisms and Model Diversity of Trade-Wind Shallow Cumulus Cloud Feedbacks: A Review

NASA Astrophysics Data System (ADS)

Vial, Jessica; Bony, Sandrine; Stevens, Bjorn; Vogel, Raphaela

Shallow cumulus clouds in the trade-wind regions are at the heart of the long standing uncertainty in climate sensitivity estimates. In current climate models, cloud feedbacks are strongly influenced by cloud-base cloud amount in the trades. Therefore, understanding the key factors controlling cloudiness near cloud-base in shallow convective regimes has emerged as an important topic of investigation. We review physical understanding of these key controlling factors and discuss the value of the different approaches that have been developed so far, based on global and high-resolution model experimentations and process-oriented analyses across a range of models and for observations. The trade-wind cloud feedbacks appear to depend on two important aspects: (1) how cloudiness near cloud-base is controlled by the local interplay between turbulent, convective and radiative processes; (2) how these processes interact with their surrounding environment and are influenced by mesoscale organization. Our synthesis of studies that have explored these aspects suggests that the large diversity of model responses is related to fundamental differences in how the processes controlling trade cumulus operate in models, notably, whether they are parameterized or resolved. In models with parameterized convection, cloudiness near cloud-base is very sensitive to the vigor of convective mixing in response to changes in environmental conditions. This is in contrast with results from high-resolution models, which suggest that cloudiness near cloud-base is nearly invariant with warming and independent of large-scale environmental changes. Uncertainties are difficult to narrow using current observations, as the trade cumulus variability and its relation to large-scale environmental factors strongly depend on the time and/or spatial scales at which the mechanisms are evaluated. New opportunities for testing physical understanding of the factors controlling shallow cumulus cloud responses using observations and highresolution modeling on large domains are discussed.

KF-finder: identification of key factors from host-microbial networks in cervical cancer.

PubMed

Hu, Jialu; Gao, Yiqun; Zheng, Yan; Shang, Xuequn

2018-04-24

The human body is colonized by a vast number of microbes. Microbiota can benefit many normal life processes, but can also cause many diseases by interfering the regular metabolism and immune system. Recent studies have demonstrated that the microbial community is closely associated with various types of cell carcinoma. The search for key factors, which also refer to cancer causing agents, can provide an important clue in understanding the regulatory mechanism of microbiota in uterine cervix cancer. In this paper, we investigated microbiota composition and gene expression data for 58 squamous and adenosquamous cell carcinoma. A host-microbial covariance network was constructed based on the 16s rRNA and gene expression data of the samples, which consists of 259 abundant microbes and 738 differentially expressed genes (DEGs). To search for risk factors from host-microbial networks, the method of bi-partite betweenness centrality (BpBC) was used to measure the risk of a given node to a certain biological process in hosts. A web-based tool KF-finder was developed, which can efficiently query and visualize the knowledge of microbiota and differentially expressed genes (DEGs) in the network. Our results suggest that prevotellaceade, tissierellaceae and fusobacteriaceae are the most abundant microbes in cervical carcinoma, and the microbial community in cervical cancer is less diverse than that of any other boy sites in health. A set of key risk factors anaerococcus, hydrogenophilaceae, eubacterium, PSMB10, KCNIP1 and KRT13 have been identified, which are thought to be involved in the regulation of viral response, cell cycle and epithelial cell differentiation in cervical cancer. It can be concluded that permanent changes of microbiota composition could be a major force for chromosomal instability, which subsequently enables the effect of key risk factors in cancer. All our results described in this paper can be freely accessed from our website at http://www.nwpu-bioinformatics.com/KF-finder/ .

ChoiceKey: a real-time speech recognition program for psychology experiments with a small response set.

PubMed

Donkin, Christopher; Brown, Scott D; Heathcote, Andrew

2009-02-01

Psychological experiments often collect choice responses using buttonpresses. However, spoken responses are useful in many cases-for example, when working with special clinical populations, or when a paradigm demands vocalization, or when accurate response time measurements are desired. In these cases, spoken responses are typically collected using a voice key, which usually involves manual coding by experimenters in a tedious and error-prone manner. We describe ChoiceKey, an open-source speech recognition package for MATLAB. It can be optimized by training for small response sets and different speakers. We show ChoiceKey to be reliable with minimal training for most participants in experiments with two different responses. Problems presented by individual differences, and occasional atypical responses, are examined, and extensions to larger response sets are explored. The ChoiceKey source files and instructions may be downloaded as supplemental materials for this article from brm.psychonomic-journals.org/content/supplemental.

Hypoxia inducible factor 1 (HIF-1) and cardioprotection

PubMed Central

Tekin, Demet; Dursun, Ali D; Xi, Lei

2010-01-01

Since its discovery in early 1990s, hypoxia inducible factor 1 (HIF-1) has been increasingly recognized for its key role in transcriptional control of more than a hundred genes that regulate a wide-spectrum of cellular functional events, including angiogenesis, vasomotor control, glucose and energy metabolism, erythropoiesis, iron homeostasis, pH regulation, cell proliferation and viability. Evidence accumulated during the past 7 years suggests a critical role for HIF-1α in mediating cardioprotection. The purpose of our present article is to provide an updated overview on this important regulator of gene expression in the cellular stress-responsive and adaptive process. We have particularly emphasized the involvement of HIF-1 in the induction of cardioprotective molecules, such as inducible nitric oxide synthase (iNOS), hemeoxygenase 1 (HO-1), and erythropoietin (EPO), which in turn alleviate myocardial damages caused by harmful events such as ischemia-reperfusion injury. Despite these advances, further in-depth studies are needed to elucidate the possible coordination or interaction between HIF-1α and other key transcription factors in regulating protein expression that leads to cardioprotection. PMID:20711226

Why different countries manage death differently: a comparative analysis of modern urban societies.

PubMed

Walter, Tony

2012-03-01

The sociology of death, dying and bereavement tends to take as its implicit frame either the nation state or a homogenous modernity. Between-nation differences in the management of death and dying are either ignored or untheorized. This article seeks to identify the factors that can explain both similarities and differences in the management of death between different modern western nations. Structural factors which affect all modern nations include urbanization and the division of labour leading to the dominance of professionals, migration, rationality and bureaucracy, information technology and the risk society. How these sociologically familiar structural features are responded to, however, depends on national histories, institutions and cultures. Historically, key transitional periods to modernity, different in different nations, necessitated particular institutional responses in the management of dying and dead bodies. Culturally, key factors include individualism versus collectivism, religion, secularization, boundary regulation, and expressivism. Global flows of death practices depend significantly on subjugated nations' perceptions of colonialism, neo-colonialism and modernity, which can lead to a dominant power's death practices being either imitated or rejected. © London School of Economics and Political Science 2012.

Examination of the influence of environmental factors on contaminant vapor concentration attenuation factors using the U.S. EPA's vapor intrusion database.

PubMed

Yao, Yijun; Shen, Rui; Pennell, Kelly G; Suuberg, Eric M

2013-01-15

Those charged with the responsibility of estimating the risk posed by vapor intrusion (VI) processes have often looked to information contained in the U.S. Environmental Protection Agency (EPA)'s VI database for insight. Indoor air concentration attenuation factors have always been a key focus of this database, but the roles of different environmental factors in these attenuation processes are still unclear. This study aims to examine the influences of these factors in the context of the information in the VI database. The database shows that the attenuation factors vary over many orders of magnitude and that no simple statistical fluctuation around any typical mean value exists. Thus far, no simple explanation of this phenomenon has been presented. This paper examines various possible contributing factors to the enormous range of observed values, looking at which ones can plausibly contribute to explaining them.

Crisis response to schools.

PubMed

Johnson, K

2000-01-01

While community based crisis response teams offer needed resources to schools impacted by crisis, they are often not asked to help. Reports from crisis team leaders at the school shooting incidents at James W. Parker Middle School, Edinboro, Pennsylvania and Columbine High School, Littleton, Colorado are contrasted regarding utilization of community resources. Factors limiting the usefulness of community based teams include unfamiliarity with school organization, culture, and procedures. Key differences in school vs. community team precepts, decision-making, and strategic paradigms render team coordination difficult. Successful cross training presents opportunities for school-community partnership and utilization of community teams for school duty.

Of lemmings and snowshoe hares: the ecology of northern Canada

PubMed Central

Krebs, Charles J.

2011-01-01

Two population oscillations dominate terrestrial community dynamics in northern Canada. In the boreal forest, the snowshoe hare (Lepus americanus) fluctuates in cycles with an 8–10 year periodicity and in tundra regions lemmings typically fluctuate in cycles with a 3–4 year periodicity. I review 60 years of research that has uncovered many of the causes of these population cycles, outline areas of controversy that remain and suggest key questions to address. Lemmings are keystone herbivores in tundra ecosystems because they are a key food resource for many avian and mammalian predators and are a major consumer of plant production. There remains much controversy over the role of predation, food shortage and social interactions in causing lemming cycles. Predation is well documented as a significant mortality factor limiting numbers. Food shortage is less likely to be a major limiting factor on population growth in lemmings. Social interactions might play a critical role in reducing the rate of population growth as lemming density rises. Snowshoe hares across the boreal forest are a key food for many predators and their cycles have been the subject of large-scale field experiments that have pinpointed predation as the key limiting factor causing these fluctuations. Predators kill hares directly and indirectly stress them by unsuccessful pursuits. Stress reduces the reproductive rate of female hares and is transmitted to their offspring who also suffer reduced reproductive rates. The maternal effects produced by predation risk induce a time lag in the response of hare reproductive rate to density, aiding the cyclic dynamics. PMID:20980307

Abscisic Acid (ABA) Regulation of Arabidopsis SR Protein Gene Expression

PubMed Central

Cruz, Tiago M. D.; Carvalho, Raquel F.; Richardson, Dale N.; Duque, Paula

2014-01-01

Serine/arginine-rich (SR) proteins are major modulators of alternative splicing, a key generator of proteomic diversity and flexible means of regulating gene expression likely to be crucial in plant environmental responses. Indeed, mounting evidence implicates splicing factors in signal transduction of the abscisic acid (ABA) phytohormone, which plays pivotal roles in the response to various abiotic stresses. Using real-time RT-qPCR, we analyzed total steady-state transcript levels of the 18 SR and two SR-like genes from Arabidopsis thaliana in seedlings treated with ABA and in genetic backgrounds with altered expression of the ABA-biosynthesis ABA2 and the ABA-signaling ABI1 and ABI4 genes. We also searched for ABA-responsive cis elements in the upstream regions of the 20 genes. We found that members of the plant-specific SC35-Like (SCL) Arabidopsis SR protein subfamily are distinctively responsive to exogenous ABA, while the expression of seven SR and SR-related genes is affected by alterations in key components of the ABA pathway. Finally, despite pervasiveness of established ABA-responsive promoter elements in Arabidopsis SR and SR-like genes, their expression is likely governed by additional, yet unidentified cis-acting elements. Overall, this study pinpoints SR34, SR34b, SCL30a, SCL28, SCL33, RS40, SR45 and SR45a as promising candidates for involvement in ABA-mediated stress responses. PMID:25268622

Attenuation of Counterregulatory Responses to Recurrent Hypoglycemia by Active Thalamic Inhibition

PubMed Central

Arbelaez, Ana Maria; Powers, William J.; Videen, Tom O.; Price, Joseph L.; Cryer, Philip E.

2008-01-01

Objective Hypoglycemia, the limiting factor in the glycemic management of diabetes, is the result of the interplay of therapeutic insulin excess and compromised glycemic defenses. The key feature of the latter is an attenuated sympathoadrenal response to hypoglycemia that typically follows an episode of recent antecedent iatrogenic hypoglycemia, a phenomenon termed hypoglycemia-associated autonomic failure (HAAF) in diabetes. We investigated the role of cerebral mechanisms in HAAF by measuring regional brain activation during recurrent hypoglycemia with attenuated counterregulatory responses and comparing it to initial hypoglycemia in healthy individuals. Research Design and Methods We used [15O]water and positron emission tomography to measure regional cerebral blood flow (CBF) as a marker of brain synaptic activity during hyperinsulinemic hypoglycemic clamps (55 mg/dL [3.0 mmol/L]) in the naïve condition (Day 1) and after ∼24 hours of interval interprandial hypoglycemia (Day 2) in nine healthy adults. Results Interval hypoglycemia produced attenuated sympathoadrenal, symptomatic and other counterregulatory responses to hypoglycemia on Day 2, a model of HAAF. Synaptic activity in the dorsal midline thalamus during hypoglycemia was significantly greater on Day 2 than Day 1 (P=0.004). Conclusion Greater synaptic activity associated with attenuated counterregulatory responses indicates that the dorsal midline thalamus plays an active inhibitory role in reducing sympathoadrenal and symptomatic responses to hypoglycemia when previous hypoglycemia has occurred, the key feature of HAAF in diabetes. PMID:18003752

Soybean Roots Grown under Heat Stress Show Global Changes in Their Transcriptional and Proteomic Profiles

DOE PAGES

Valdés-López, Oswaldo; Batek, Josef; Gomez-Hernandez, Nicolas; ...

2016-04-25

Heat stress is likely to be a key factor in the negative impact of climate change on crop production. Heat stress significantly influences the functions of roots, which provide support, water, and nutrients to other plant organs. Likewise, roots play an important role in the establishment of symbiotic associations with different microorganisms. Despite the physiological relevance of roots, few studies have examined their response to heat stress. Here in this study, we performed genome-wide transcriptomic and proteomic analyses on isolated root hairs, which are a single, epidermal cell type, and compared their response to stripped roots. On average, we identifiedmore » 1849 and 3091 genes differentially regulated in root hairs and stripped roots, respectively, in response to heat stress. Our gene regulatory module analysis identified 10 key modules that might control the majority of the transcriptional response to heat stress. We also conducted proteomic analysis on membrane fractions isolated from root hairs and compared these responses to stripped roots. These experiments identified a variety of proteins whose expression changed within 3 h of application of heat stress. Most of these proteins were predicted to play a significant role in thermo-tolerance, as well as in chromatin remodeling and post-transcriptional regulation. In conclusion, the data presented represent an in-depth analysis of the heat stress response of a single cell type in soybean.« less

Managing the sugar factory: A new feather in the cap for nuclear factor Y.

PubMed

Sen, Sabyasachi; Das, Chandrima

2018-05-18

Gluconeogenesis in the liver converts lipids and several other noncarbohydrate precursors into glucose, ensuring that blood sugar levels are maintained at healthy levels, especially during fasting. Effective regulation of gluconeogenesis is therefore critical for maintaining systemic metabolic homeostasis. Zhang and colleagues have discovered that the ubiquitous transcriptional regulator nuclear factor Y (NF-Y) confers cAMP responsiveness to key gluconeogenic genes and up-regulates hepatic glucose production. The study expands our understanding of transcriptional regulation of hepatic gluconeogenesis and also presents critical insights into the function of NF-Y in the liver. © 2018 Sen and Das.

Maximizing the benefits of antiretroviral therapy for key affected populations

PubMed Central

Grubb, Ian R; Beckham, Sarah W; Kazatchkine, Michel; Thomas, Ruth M; Albers, Eliot R; Cabral, Mauro; Lange, Joep; Vella, Stefano; Kurian, Manoj; Beyrer, Chris

2014-01-01

Introduction Scientific research has demonstrated the clinical benefits of earlier initiation of antiretroviral treatment (ART), and that ART can markedly reduce HIV transmission to sexual partners. Ensuring universal access to ART for those who need it has long been a core principle of the HIV response, and extending the benefits of ART to key populations is critical to increasing the impact of ART and the overall effectiveness of the HIV response. However, this can only be achieved through coordinated efforts to address political, social, legal and economic barriers that key populations face in accessing HIV services. Discussion Recent analyses show that HIV prevalence levels among key populations are far higher than among the general population, and they experience a range of biological and behavioural factors, and social, legal and economic barriers that increase their vulnerability to HIV and have resulted in alarmingly low ART coverage. World Health Organization 2014 consolidated guidance on HIV among key populations offers the potential for increased access to ART by key populations, following the same principles as for the general adult population. However, it should not be assumed that key populations will achieve greater access to ART unless stigma, discrimination and punitive laws, policies and practices that limit access to ART and other HIV interventions in many countries are addressed. Conclusions Rights-based approaches and investments in critical enablers, such as supportive legal and policy environments, are essential to enable wider access to ART and other HIV interventions for key populations. The primary objective of ART should always be to treat the person living with HIV; prevention is an important, additional benefit. ART should be provided only with informed consent. The preventive benefits of treatment must not be used as a pretext for failure to provide other necessary HIV programming for key populations, including comprehensive harm reduction and other prevention interventions tailored to meet the needs of key populations. An end to AIDS is only possible if we overcome the barriers of criminalization, stigma and discrimination that remain key drivers of the HIV epidemics among key populations. PMID:25043380

Maximizing the benefits of antiretroviral therapy for key affected populations.

PubMed

Grubb, Ian R; Beckham, Sarah W; Kazatchkine, Michel; Thomas, Ruth M; Albers, Eliot R; Cabral, Mauro; Lange, Joep; Vella, Stefano; Kurian, Manoj; Beyrer, Chris

2014-01-01

Scientific research has demonstrated the clinical benefits of earlier initiation of antiretroviral treatment (ART), and that ART can markedly reduce HIV transmission to sexual partners. Ensuring universal access to ART for those who need it has long been a core principle of the HIV response, and extending the benefits of ART to key populations is critical to increasing the impact of ART and the overall effectiveness of the HIV response. However, this can only be achieved through coordinated efforts to address political, social, legal and economic barriers that key populations face in accessing HIV services. Recent analyses show that HIV prevalence levels among key populations are far higher than among the general population, and they experience a range of biological and behavioural factors, and social, legal and economic barriers that increase their vulnerability to HIV and have resulted in alarmingly low ART coverage. World Health Organization 2014 consolidated guidance on HIV among key populations offers the potential for increased access to ART by key populations, following the same principles as for the general adult population. However, it should not be assumed that key populations will achieve greater access to ART unless stigma, discrimination and punitive laws, policies and practices that limit access to ART and other HIV interventions in many countries are addressed. Rights-based approaches and investments in critical enablers, such as supportive legal and policy environments, are essential to enable wider access to ART and other HIV interventions for key populations. The primary objective of ART should always be to treat the person living with HIV; prevention is an important, additional benefit. ART should be provided only with informed consent. The preventive benefits of treatment must not be used as a pretext for failure to provide other necessary HIV programming for key populations, including comprehensive harm reduction and other prevention interventions tailored to meet the needs of key populations. An end to AIDS is only possible if we overcome the barriers of criminalization, stigma and discrimination that remain key drivers of the HIV epidemics among key populations.

[Horizon scanning in preparation for future health threats: a pilot exercise conducted by the French Institute for Public Health Surveillance in 2014].

PubMed

Eilstein, Daniel; Xerri, Bertrand; Viso, Anne-Catherine; Therre, Hélène; Gorza, Maud; Fuchs, Doriane; Pozuelos, Jérôme; Ioos, Sophie; Che, Didier; Bertrand, Edwige; El Yamani, Mounia; Empereur-Bissonnet, Pascal; Duport, Nicolas; Desenclos, Jean-Claude

2016-01-01

Background: Health surveillance is a reactive process, with no real hindsight for dealing with signals and alerts. It may fail to detect more radical changes with a major medium-term or long-term impact on public health. To increase proactivity, the French Institute for Public Health Surveillance has opted for a prospective monitoring approach.Methods: Several steps were necessary: 1) Identification of public health determinants. 2) Identification of key variables based on a combination of determinants. Variables were classified into three groups (health event trigger factors, dissemination factors and response factors) and were submitted to future development assumptions. 3) Identification, in each of the three groups, of micro-scenarios derived from variable trends. 4) Identification of macro-scenarios, each built from the three micro-scenarios for each of the three groups. 5) Identification of issues for the future of public health.Results: The exercise identified 22 key variables, 17 micro-scenarios and 5 macro-scenarios. The topics retained relate to issues on social and territorial health inequalities, health burden, individual and collective responsibilities in terms of health, ethical aspects, emerging phenomena, ‘Big data’, data mining, new health technologies, interlocking of analysis scales.Conclusions: The approach presented here guides the programming of activities of a health safety agency, particularly for monitoring and surveillance. By describing possible future scenarios, health surveillance can help decision-makers to influence the context towards one or more favourable futures.

Society for Neuro-Oncology 2014 annual meeting updates on central nervous system metastases.

PubMed

Lukas, Rimas V; Mehta, Minesh P; Lesniak, Maciej S

2015-06-01

The 19th Annual Meeting of the Society for Neuro-Oncology (SNO) took place in November of 2014. The focus of many abstracts, as well as the Education Day, was on recent advances in the study of central nervous system (CNS) metastases. Key studies evaluating the factors in tumors and their microenvironment associated with the development and growth of brain metastases are reviewed. Studies investigating the factors that independently influence survival in participants with brain metastases are presented. The Response Assessment for Neuro-Oncology criteria for brain metastases (RANO-BM) and the Neurological Assessment in Neuro-Oncology (NANO) criteria, which were both presented, are recapped. Studies are reviewed evaluating factors that influence survival outcomes in participants with brain metastases who were treated with radiotherapy. Studies investigating the potential risk of radiation necrosis with the combination of radiotherapy and immunotherapies are presented. Brain metastases-focused subset analyses from the ASCEND-1 trial for ALK-translocated non-small cell lung cancer are presented. Preclinical and clinical work on solid tumor leptomeningeal carcinomatosis is also covered. An overview is provided of treatment- related toxicities as well as important concepts that may influence strategies to protect against these toxicities. Key concepts regarding tumor biology, prognostication, response assessment, therapeutic management, and sequelae of treatment for CNS metastases are summarized. Advances in our understanding of the basic and clinical science of CNS metastases have the potential to improve outcomes for patients.

Deficiency of Mannose-Binding Lectin Greatly Increases Susceptibility to Postburn Infection with Pseudomonas aeruginosa1

PubMed Central

Møller-Kristensen, Mette; Eddie Ip, W. K.; Shi, Lei; Gowda, Lakshmi D.; Hamblin, Michael R.; Thiel, Steffen; Jensenius, Jens Chr.; Ezekowitz, R. Alan B.; Takahashi, Kazue

2011-01-01

Burn injury disrupts the mechanical and biological barrier that the skin presents against infection by symbionts like the Pseudomonas aeruginosa, a Gram-negative bacteria. A combination of local factors, antimicrobial peptides, and resident effector cells form the initial response to mechanical injury of the skin. This activity is followed by an inflammatory response that includes influx of phagocytes and serum factors, such as complement and mannose-binding lectin (MBL), which is a broad-spectrum pattern recognition molecule that plays a key role in innate immunity. A growing consensus from studies in humans and mice suggests that lack of MBL together with other comorbid factors predisposes the host to infection. In this study we examined whether MBL deficiency increases the risk of P. aeruginosa infection in a burned host. We found that both wild-type and MBL null mice were resistant to a 5% total body surface area burn alone or s.c. infection with P. aeruginosa alone. However, when mice were burned then inoculated s.c. with P. aeruginosa at the burn site, all MBL null mice died by 42 h from septicemia, whereas only one-third of wild-type mice succumbed (p = 0.0005). This result indicates that MBL plays a key role in containing and preventing a systemic spread of P. aeruginosa infection following burn injury and suggests that MBL deficiency in humans maybe a premorbid variable in the predisposition to infection in burn victims. PMID:16424207

Mechanism of enhanced hematopoietic response by soluble beta-glucan SCG in cyclophosphamide-treated mice.

PubMed

Harada, Toshie; Kawaminami, Hiromi; Miura, Noriko N; Adachi, Yoshiyuki; Nakajima, Mitsuhiro; Yadomae, Toshiro; Ohno, Naohito

2006-01-01

SCG is a major 6-branched 1,3-beta-D-glucan in Sparassis crispa Fr. SCG shows antitumor activity and also enhances the hematopoietic response in cyclophosphamide (CY)-treated mice. In the present study, the molecular mechanism of the enhancement of the hematopoietic response was investigated. The levels of interferon-(IFN-)gamma, tumor necrosis factor-(TNF-)alpha, granulocyte-macrophage-colony stimulating factor (GM-CSF), interleukin-(IL-) 6 and IL-12p70 were significantly increased by SCG in CY-treated mice. GM-CSF production in the splenocytes from the CY-treated mice was higher than that in normal mice regardless of SCG stimulation. Neutralizing GM-CSF significantly inhibited the induction of IFN-gamma, TNF-alpha and IL-12p70 by SCG. The level of cytokine induction by SCG was regulated by the amount of endogenous GM-CSF produced in response to CY treatment in a dose-dependent manner. The expression of beta-glucan receptors, such as CR3 and dectin-1, was up-regulated by CY treatment. Blocking dectin-1 significantly inhibited the induction of TNF-alpha and IL-12p70 production by SCG. Taken together, these results suggest that the key factors in the cytokine induction in CY-treated mice were the enhanced levels of both endogenous GM-CSF production and dectin-1 expression.

Petri Net computational modelling of Langerhans cell Interferon Regulatory Factor Network predicts their role in T cell activation.

PubMed

Polak, Marta E; Ung, Chuin Ying; Masapust, Joanna; Freeman, Tom C; Ardern-Jones, Michael R

2017-04-06

Langerhans cells (LCs) are able to orchestrate adaptive immune responses in the skin by interpreting the microenvironmental context in which they encounter foreign substances, but the regulatory basis for this has not been established. Utilising systems immunology approaches combining in silico modelling of a reconstructed gene regulatory network (GRN) with in vitro validation of the predictions, we sought to determine the mechanisms of regulation of immune responses in human primary LCs. The key role of Interferon regulatory factors (IRFs) as controllers of the human Langerhans cell response to epidermal cytokines was revealed by whole transcriptome analysis. Applying Boolean logic we assembled a Petri net-based model of the IRF-GRN which provides molecular pathway predictions for the induction of different transcriptional programmes in LCs. In silico simulations performed after model parameterisation with transcription factor expression values predicted that human LC activation of antigen-specific CD8 T cells would be differentially regulated by epidermal cytokine induction of specific IRF-controlled pathways. This was confirmed by in vitro measurement of IFN-γ production by activated T cells. As a proof of concept, this approach shows that stochastic modelling of a specific immune networks renders transcriptome data valuable for the prediction of functional outcomes of immune responses.

Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge.

PubMed

Kiecolt-Glaser, Janice K

2010-05-01

Inflammation is the common link among the leading causes of death. Mechanistic studies have shown how various dietary components can modulate key pathways to inflammation, including sympathetic activity, oxidative stress, transcription factor nuclear factor-kappaB activation, and proinflammatory cytokine production. Behavioral studies have demonstrated that stressful events and depression can also influence inflammation through these same processes. If the joint contributions of diet and behavior to inflammation were simply additive, they would be important. However, several far more intriguing interactive possibilities are discussed: stress influences food choices; stress can enhance maladaptive metabolic responses to unhealthy meals; and diet can affect mood as well as proinflammatory responses to stressors. Furthermore, because the vagus nerve innervates tissues involved in the digestion, absorption, and metabolism of nutrients, vagal activation can directly and profoundly influence metabolic responses to food, as well as inflammation; in turn, both depression and stress have well-documented negative effects on vagal activation, contributing to the lively interplay between the brain and the gut. As one example, omega-3 fatty acid intake can boost mood and vagal tone, dampen nuclear factor-kappaB activation and responses to endotoxin, and modulate the magnitude of inflammatory responses to stressors. A better understanding of how stressors, negative emotions, and unhealthy meals work together to enhance inflammation will benefit behavioral and nutritional research, as well as the broader biomedical community.

A decision framework for coordinating bioterrorism planning: lessons from the BioNet program.

PubMed

Manley, Dawn K; Bravata, Dena M

2009-01-01

Effective disaster preparedness requires coordination across multiple organizations. This article describes a detailed framework developed through the BioNet program to facilitate coordination of bioterrorism preparedness planning among military and civilian decision makers. The authors and colleagues conducted a series of semistructured interviews with civilian and military decision makers from public health, emergency management, hazardous material response, law enforcement, and military health in the San Diego area. Decision makers used a software tool that simulated a hypothetical anthrax attack, which allowed them to assess the effects of a variety of response actions (eg, issuing warnings to the public, establishing prophylaxis distribution centers) on performance metrics. From these interviews, the authors characterized the information sources, technologies, plans, and communication channels that would be used for bioterrorism planning and responses. The authors used influence diagram notation to describe the key bioterrorism response decisions, the probabilistic factors affecting these decisions, and the response outcomes. The authors present an overview of the response framework and provide a detailed assessment of two key phases of the decision-making process: (1) pre-event planning and investment and (2) incident characterization and initial responsive measures. The framework enables planners to articulate current conditions; identify gaps in existing policies, technologies, information resources, and relationships with other response organizations; and explore the implications of potential system enhancements. Use of this framework could help decision makers execute a locally coordinated response by identifying the critical cues of a potential bioterrorism event, the information needed to make effective response decisions, and the potential effects of various decision alternatives.

Dual Roles for Ikaros in Regulation of Macrophage Chromatin State and Inflammatory Gene Expression.

PubMed

Oh, Kyu-Seon; Gottschalk, Rachel A; Lounsbury, Nicolas W; Sun, Jing; Dorrington, Michael G; Baek, Songjoon; Sun, Guangping; Wang, Ze; Krauss, Kathleen S; Milner, Joshua D; Dutta, Bhaskar; Hager, Gordon L; Sung, Myong-Hee; Fraser, Iain D C

2018-06-13

Macrophage activation by bacterial LPS leads to induction of a complex inflammatory gene program dependent on numerous transcription factor families. The transcription factor Ikaros has been shown to play a critical role in lymphoid cell development and differentiation; however, its function in myeloid cells and innate immune responses is less appreciated. Using comprehensive genomic analysis of Ikaros-dependent transcription, DNA binding, and chromatin accessibility, we describe unexpected dual repressor and activator functions for Ikaros in the LPS response of murine macrophages. Consistent with the described function of Ikaros as transcriptional repressor, Ikzf1 -/- macrophages showed enhanced induction for select responses. In contrast, we observed a dramatic defect in expression of many delayed LPS response genes, and chromatin immunoprecipitation sequencing analyses support a key role for Ikaros in sustained NF-κB chromatin binding. Decreased Ikaros expression in Ikzf1 +/- mice and human cells dampens these Ikaros-enhanced inflammatory responses, highlighting the importance of quantitative control of Ikaros protein level for its activator function. In the absence of Ikaros, a constitutively open chromatin state was coincident with dysregulation of LPS-induced chromatin remodeling, gene expression, and cytokine responses. Together, our data suggest a central role for Ikaros in coordinating the complex macrophage transcriptional program in response to pathogen challenge.

Modulation of innate immune responses by Yersinia type III secretion system translocators and effectors.

PubMed

Bliska, James B; Wang, Xiaoying; Viboud, Gloria I; Brodsky, Igor E

2013-10-01

The innate immune system of mammals responds to microbial infection through detection of conserved molecular determinants called 'pathogen-associated molecular patterns' (PAMPs). Pathogens use virulence factors to counteract PAMP-directed responses. The innate immune system can in turn recognize signals generated by virulence factors, allowing for a heightened response to dangerous pathogens. Many Gram-negative bacterial pathogens encode type III secretion systems (T3SSs) that translocate effector proteins, subvert PAMP-directed responses and are critical for infection. A plasmid-encoded T3SS in the human-pathogenic Yersinia species translocates seven effectors into infected host cells. Delivery of effectors by the T3SS requires plasma membrane insertion of two translocators, which are thought to form a channel called a translocon. Studies of the Yersinia T3SS have provided key advances in our understanding of how innate immune responses are generated by perturbations in plasma membrane and other signals that result from translocon insertion. Additionally, studies in this system revealed that effectors function to inhibit innateimmune responses resulting from insertion of translocons into plasma membrane. Here, we review these advances with the goal of providing insight into how a T3SS can activate and inhibit innate immune responses, allowing a virulent pathogen to bypass host defences. © 2013 John Wiley & Sons Ltd.

Innate immune response to Burkholderia mallei

PubMed Central

Saikh, Kamal U.; Mott, Tiffany M.

2017-01-01

Purpose of review Burkholderia mallei is a facultative intracellular pathogen that causes the highly contagious and often the fatal disease, glanders. With its high rate of infectivity via aerosol and recalcitrance toward antibiotics, this pathogen is considered a potential biological threat agent. This review focuses on the most recent literature highlighting host innate immune response to B. mallei. Recent findings Recent studies focused on elucidating host innate immune responses to the novel mechanisms and virulence factors employed by B. mallei for survival. Studies suggest that pathogen proteins manipulate various cellular processes, including host ubiquitination pathways, phagosomal escape, and actin–cytoskeleton rearrangement. Immune-signaling molecules such as Toll-like receptors, nucleotode-binding oligomerization domain, myeloid differentiation primary response protein 88, and proinflammatory cytokines such as interferon-gamma and tumor necrosis factor-α, play key roles in the induction of innate immune responses. Modifications in B. mallei lipopolysaccharide, in particular, the lipid A acyl groups, stimulate immune responses via Toll-like receptor4 activation that may contribute to persistent infection. Summary Mortality is high because of septicemia and immune pathogenesis with B. mallei exposure. An effective innate immune response is critical to controlling the acute phase of the infection. Both vaccination and therapeutic approaches are necessary for complete protection against B. mallei. PMID:28177960

Krüppel-like factors are effectors of nuclear receptor signaling

PubMed Central

Knoedler, Joseph R.; Denver, Robert J.

2015-01-01

Binding of steroid and thyroid hormones to their cognate nuclear receptors (NRs) impacts virtually every aspect of postembryonic development, physiology and behavior, and inappropriate signaling by NRs may contribute to disease. While NRs regulate genes by direct binding to hormone response elements in the genome, their actions may depend on the activity of other transcription factors (TFs) that may or may not bind DNA. The Krüppel-like family of transcription factors (KLF) is an evolutionarily conserved class of DNA-binding proteins that influence many aspects of development and physiology. Several members of this family have been shown to play diverse roles in NR signaling. For example, KLFs 1) act as accessory transcription factors for NR actions, 2) regulate expression of NR genes, and 3) as gene products of primary NR response genes function as key players in NR-dependent transcriptional networks. In mouse models, deletion of different KLFs leads to aberrant transcriptional and physiological responses to hormones, underscoring the importance of these proteins in the regulation of hormonal signaling. Understanding the functional relationships between NRs and KLFs will yield important insights into mechanisms of NR signaling. In this review we present a conceptual framework for understanding how KLFs participate in NR signaling, and we provide examples of how these proteins function to effect hormone action. PMID:24642391

Macrophage migration inhibitory factor deficiency is associated with impaired killing of gram-negative bacteria by macrophages and increased susceptibility to Klebsiella pneumoniae sepsis.

PubMed

Roger, Thierry; Delaloye, Julie; Chanson, Anne-Laure; Giddey, Marlyse; Le Roy, Didier; Calandra, Thierry

2013-01-15

The cytokine macrophage migration inhibitory factor (MIF) is an important component of the early proinflammatory response of the innate immune system. However, the antimicrobial defense mechanisms mediated by MIF remain fairly mysterious. In the present study, we examined whether MIF controls bacterial uptake and clearance by professional phagocytes, using wild-type and MIF-deficient macrophages. MIF deficiency did not affect bacterial phagocytosis, but it strongly impaired the killing of gram-negative bacteria by macrophages and host defenses against gram-negative bacterial infection, as shown by increased mortality in a Klebsiella pneumonia model. Consistent with MIF's regulatory role of Toll-like 4 expression in macrophages, MIF-deficient cells stimulated with lipopolysaccharide or Escherichia coli exhibited reduced nuclear factor κB activity and tumor necrosis factor (TNF) production. Addition of recombinant MIF or TNF corrected the killing defect of MIF-deficient macrophages. Together, these data show that MIF is a key mediator of host responses against gram-negative bacteria, acting in part via a modulation of bacterial killing by macrophages.

Cryptochrome 1 interacts with PIF4 to regulate high temperature-mediated hypocotyl elongation in response to blue light

PubMed Central

Ma, Dingbang; Li, Xu; Guo, Yongxia; Chu, Jingfang; Fang, Shuang; Yan, Cunyu; Noel, Joseph P.; Liu, Hongtao

2016-01-01

Cryptochrome 1 (CRY1) is a blue light receptor that mediates primarily blue-light inhibition of hypocotyl elongation. Very little is known of the mechanisms by which CRY1 affects growth. Blue light and temperature are two key environmental signals that profoundly affect plant growth and development, but how these two abiotic factors integrate remains largely unknown. Here, we show that blue light represses high temperature-mediated hypocotyl elongation via CRY1. Furthermore, CRY1 interacts directly with PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) in a blue light-dependent manner to repress the transcription activity of PIF4. CRY1 represses auxin biosynthesis in response to elevated temperature through PIF4. Our results indicate that CRY1 signal by modulating PIF4 activity, and that multiple plant photoreceptors [CRY1 and PHYTOCHROME B (PHYB)] and ambient temperature can mediate morphological responses through the same signaling component—PIF4. PMID:26699514

AIDS legislation--turning up the heat?

PubMed Central

Kirby, M D

1986-01-01

This paper is not about the medical condition of AIDS. Nor is it about the history of the condition since it was first reported in Atlanta, Georgia in 1981. It looks rather, at the catalogue of legislative and other legal responses to the spread of AIDS. The paper analyses the AIDS condition in its historical context. The hysteria accompanying the outbreak of AIDS is contrasted with the similar hysteria associated with other previous epidemics experienced in Australia over the past two centuries. The paper categorises the responses of lawmakers to the condition, according to the approach taken; from 'full blast', through 'moderate heat' to 'low key' or an attempt to avoid or minimise legal intervention. It is suggested that the appropriate response should depend upon such factors as the present magnitude of the condition, its likely future course, the availability of cures and protections against its spread and objectives being sought by intervention. Unless these factors are taken into account gross over-reaction can occur, causing social disruption and much personal injustice. PMID:3806630

Role of immune cells in obesity induced low grade inflammation and insulin resistance.

PubMed

Asghar, Ambreen; Sheikh, Nadeem

2017-05-01

The frequency of obesity is enormously growing worldwide. Obesity results when energy intake exceeds, energy expenditure. Excess adiposity is a major risk factor in the progress of various metabolic disorders accounting insulin resistance, hypertension, Type 2 diabetes, nonalcoholic fatty liver disease, polycystic ovarian disease and several types of cancers. Obesity is characterized by pro-inflammatory condition in which hypertrophied adipose tissue along with immune cells contribute to increase the level of pro-inflammatory cytokines. Immune cells are the key players in inducing low grade chronic inflammation in obesity and are main factor responsible for pathogenesis of insulin resistance resulting Type 2 diabetes. The current review is aimed to investigate the mechanism of pro-inflammatory responses and insulin resistance involving immune cells and their products in obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

Transcriptome and metabolite analysis identifies nitrogen utilization genes in tea plant (Camellia sinensis).

PubMed

Li, Wei; Xiang, Fen; Zhong, Micai; Zhou, Lingyun; Liu, Hongyan; Li, Saijun; Wang, Xuewen

2017-05-10

Applied nitrogen (N) fertilizer significantly increases the leaf yield. However, most N is not utilized by the plant, negatively impacting the environment. To date, little is known regarding N utilization genes and mechanisms in the leaf production. To understand this, we investigated transcriptomes using RNA-seq and amino acid levels with N treatment in tea (Camellia sinensis), the most popular beverage crop. We identified 196 and 29 common differentially expressed genes in roots and leaves, respectively, in response to ammonium in two tea varieties. Among those genes, AMT, NRT and AQP for N uptake and GOGAT and GS for N assimilation were the key genes, validated by RT-qPCR, which expressed in a network manner with tissue specificity. Importantly, only AQP and three novel DEGs associated with stress, manganese binding, and gibberellin-regulated transcription factor were common in N responses across all tissues and varieties. A hypothesized gene regulatory network for N was proposed. A strong statistical correlation between key genes' expression and amino acid content was revealed. The key genes and regulatory network improve our understanding of the molecular mechanism of N usage and offer gene targets for plant improvement.

Expression of AtWRKY33 encoding a pathogen- or PAMP-responsive WRKY transcription factor is regulated by a composite DNA motif containing W box elements.

PubMed

Lippok, Bernadette; Birkenbihl, Rainer P; Rivory, Gaelle; Brümmer, Janna; Schmelzer, Elmon; Logemann, Elke; Somssich, Imre E

2007-04-01

WRKY transcription factors regulate distinct parts of the plant defense transcriptome. Expression of many WRKY genes themselves is induced by pathogens or pathogen-mimicking molecules. Here, we demonstrate that Arabidopsis WRKY33 responds to various stimuli associated with plant defense as well as to different kinds of phytopathogens. Although rapid pathogen-induced AtWRKY33 expression does not require salicylic acid (SA) signaling, it is dependent on PAD4, a key regulator upstream of SA. Activation of AtWRKY33 is independent of de novo protein synthesis, suggesting that it is at least partly under negative regulatory control. We show that a set of three WRKY-specific cis-acting DNA elements (W boxes) within the AtWRKY33 promoter is required for efficient pathogen- or PAMP-triggered gene activation. This strongly indicates that WRKY transcription factors are major components of the regulatory machinery modulating immediate to early expression of this gene in response to pathogen attack.

PIF4 and PIF5 transcription factors link blue light and auxin to regulate the phototropic response in Arabidopsis.

PubMed

Sun, Jiaqiang; Qi, Linlin; Li, Yanan; Zhai, Qingzhe; Li, Chuanyou

2013-06-01

Both blue light (BL) and auxin are essential for phototropism in Arabidopsis thaliana. However, the mechanisms by which light is molecularly linked to auxin during phototropism remain elusive. Here, we report that phytochrome interacting factoR4 (PIF4) and PIF5 act downstream of the BL sensor phototropin1 (PHOT1) to negatively modulate phototropism in Arabidopsis. We also reveal that PIF4 and PIF5 negatively regulate auxin signaling. Furthermore, we demonstrate that PIF4 directly activates the expression of the auxin/indole-3-acetic acid (IAA) genes IAA19 and IAA29 by binding to the G-box (CACGTG) motifs in their promoters. Our genetic assays demonstrate that IAA19 and IAA29, which physically interact with auxin response factor7 (ARF7), are sufficient for PIF4 to negatively regulate auxin signaling and phototropism. This study identifies a key step of phototropic signaling in Arabidopsis by showing that PIF4 and PIF5 link light and auxin.

On-line social decision making and antisocial behavior: some essential but neglected issues.

PubMed

Fontaine, Reid Griffith

2008-01-01

The last quarter century has witnessed considerable progress in the scientific study of social information processing (SIP) and aggressive behavior in children. SIP research has shown that social decision making in youth is particularly predictive of antisocial behavior, especially as children enter and progress through adolescence. In furtherance of this research, more sophisticated, elaborate models of on-line social decision making have been developed, by which various domains of evaluative judgment are hypothesized to account for both responsive decision making and behavior, as well as self-initiated, instrumental functioning. However, discussions of these models have neglected a number of key issues. In particular, the roles of nonconscious cognitive factors, learning and development, impulsivity and behavioral disinhibition, emotion, and other internal and external factors (e.g., pharmacological influences and audience effects) have been largely absent from scholarly writings. In response, this article introduces discussion of these factors and reviews their possible roles in on-line social decision making and antisocial behavior in youth.

SRF regulates craniofacial development through selective recruitment of MRTF cofactors by PDGF signaling.

PubMed

Vasudevan, Harish N; Soriano, Philippe

2014-11-10

Receptor tyrosine kinase signaling is critical for mammalian craniofacial development, but the key downstream transcriptional effectors remain unknown. We demonstrate that serum response factor (SRF) is induced by both platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) signaling in mouse embryonic palatal mesenchyme cells and that Srf neural crest conditional mutants exhibit facial clefting accompanied by proliferation and migration defects. Srf and Pdgfra mutants interact genetically in craniofacial development, but Srf and Fgfr1 mutants do not. This signal specificity is recapitulated at the level of cofactor activation: while both PDGF and FGF target gene promoters show enriched genome-wide overlap with SRF ChIP-seq peaks, PDGF selectively activates a network of MRTF-dependent cytoskeletal genes. Collectively, our results identify a role for SRF in proliferation and migration during craniofacial development and delineate a mechanism of receptor tyrosine kinase specificity mediated through differential cofactor usage, leading to a PDGF-responsive SRF-driven transcriptional program in the midface. Copyright © 2014 Elsevier Inc. All rights reserved.

Genetic variation in insulin-induced kinase signaling

PubMed Central

Wang, Isabel Xiaorong; Ramrattan, Girish; Cheung, Vivian G

2015-01-01

Individual differences in sensitivity to insulin contribute to disease susceptibility including diabetes and metabolic syndrome. Cellular responses to insulin are well studied. However, which steps in these response pathways differ across individuals remains largely unknown. Such knowledge is needed to guide more precise therapeutic interventions. Here, we studied insulin response and found extensive individual variation in the activation of key signaling factors, including ERK whose induction differs by more than 20-fold among our subjects. This variation in kinase activity is propagated to differences in downstream gene expression response to insulin. By genetic analysis, we identified cis-acting DNA variants that influence signaling response, which in turn affects downstream changes in gene expression and cellular phenotypes, such as protein translation and cell proliferation. These findings show that polymorphic differences in signal transduction contribute to individual variation in insulin response, and suggest kinase modulators as promising therapeutics for diseases characterized by insulin resistance. PMID:26202599

Investigating the effectiveness of response strategies for vulnerabilities to corruption in the chinese public construction sector.

PubMed

Shan, Ming; Chan, Albert P C; Le, Yun; Hu, Yi

2015-06-01

Response strategy is a key for preventing widespread corruption vulnerabilities in the public construction sector. Although several studies have been devoted to this area, the effectiveness of response strategies has seldom been evaluated in China. This study aims to fill this gap by investigating the effectiveness of response strategies for corruption vulnerabilities through a survey in the Chinese public construction sector. Survey data obtained from selected experts involved in the Chinese public construction sector were analyzed by factor analysis and partial least squares-structural equation modeling. Analysis results showed that four response strategies of leadership, rules and regulations, training, and sanctions, only achieved an acceptable level in preventing corruption vulnerabilities in the Chinese public construction sector. This study contributes to knowledge by improving the understanding of the effectiveness of response strategies for corruption vulnerabilities in the public construction sector of developing countries.

Molecular analyses of the principal components of response strength.

PubMed Central

Killeen, Peter R; Hall, Scott S; Reilly, Mark P; Kettle, Lauren C

2002-01-01

Killeen and Hall (2001) showed that a common factor called strength underlies the key dependent variables of response probability, latency, and rate, and that overall response rate is a good predictor of strength. In a search for the mechanisms that underlie those correlations, this article shows that (a) the probability of responding on a trial is a two-state Markov process; (b) latency and rate of responding can be described in terms of the probability and period of stochastic machines called clocked Bernoulli modules, and (c) one such machine, the refractory Poisson process, provides a functional relation between the probability of observing a response during any epoch and the rate of responding. This relation is one of proportionality at low rates and curvilinearity at higher rates. PMID:12216975

Prognostic significance of DSG3 in rectal adenocarcinoma treated with preoperative chemoradiotherapy.

PubMed

Chao, Tung-Bo; Li, Chien-Feng; Lin, Ching-Yih; Tian, Yu-Feng; Chang, I-Wei; Sheu, Ming-Jen; Lee, Ying-En; Chan, Ti-Chun; He, Hong-Lin

2016-06-01

This study aimed to investigate the prognostic significance of DSG3 and its association with response to neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer. Data mining of a publicly available dataset was performed to find genes associated with CCRT response. Immunohistochemistry was applied to evaluate DSG3 expression. The relationships between DSG3 expression and various clinicopathological parameters and survival were analyzed. The DSG3 gene was significantly associated with CCRT response. The expression of DSG3 negatively correlated with poorer tumor regression (p < 0.001) and had an independent negative impact on disease-specific survival (p = 0.011), local recurrence-free survival (p = 0.031) and metastasis-free survival (p = 0.029). DSG3 was a key prognostic factor and predictor for CCRT response in rectal cancer patients.

[General organizational issues in disaster health response].

PubMed

Pacifici, L E; Riccardo, F; De Rosa, A G; Pacini, A; Nardi, L; Russo, G; Scaroni, E

2007-01-01

Recent studies show how in the 2004-2005 period there has been an increase in natural disasters of 18% worldwide. According to a renowned author planning for disaster response is as valid as the starting hypothesis. The study of an inductive mental process in disaster response planning is the key to avoiding the invention and re-invention of the wheel for each emergency. Research in this field however is hampered by different factors one of which is data collection that during disaster response requires specific training. Standardization of data collection models with limitation of the number of variables is required as is taking into account problems related to people migration and subsequent sampling problems and retrospective analysis. Moreover poor attention to the training of the volunteers employed on the field is an issue to be considered.

Facing a Health Threat in a Complex Information Environment: A National Representative Survey Examining American Adults' Behavioral Responses to the 2009/2010 A(H1N1) Pandemic

ERIC Educational Resources Information Center

Lin, Leesa; McCloud, Rachel F.; Jung, Minsoo; Viswanath, Kasisomayajula

2018-01-01

Background: Recent A(H1N1) studies suggest that intrapersonal and interpersonal factors may exert influence on people's preventive behaviors for avoiding the flu during pandemics. Aims: Nonpharmaceutical interventions (NPIs) and vaccinations play key roles in containing disease transmission during a pandemic. We examined how intrapersonal and…

Responses of oak and other hardwood regeneration to prescribed fire: what we know as of 2005

Treesearch

Patrick H. Brose; Thomas M. Schuler; Jeffrey S. Ward

2006-01-01

An obstacle to using prescribed fire to manage mixed oak forests is the varied results of previous fire studies. It has been reported that fires enhanced, hindered, or had no effect on the competitive position of oak in the regeneration pool. We review a portion of the published literature and identify key factors that led to the relative competitiveness of oak...

Key differences between apoC-III regulation and expression in intestine and liver.

PubMed

West, Gabrielle; Rodia, Cayla; Li, Diana; Johnson, Zania; Dong, Hongli; Kohan, Alison B

2017-09-23

ApoC-III is a critical cardiovascular risk factor, and humans expressing null mutations in apoC-III are robustly protected from cardiovascular disease. Because of its critical role in elevating plasma lipids and CVD risk, hepatic apoC-III regulation has been studied at length. Considerably less is known about the factors that regulate intestinal apoC-III. In this work, we use primary murine enteroids, Caco-2 cells, and dietary studies in wild-type mice to show that intestinal apoC-III expression does not change in response to fatty acids, glucose, or insulin administration, in contrast to hepatic apoC-III. Intestinal apoC-III is not sensitive to changes in FoxO1 expression (which is itself very low in the intestine, as is FoxO1 target IGFBP-1), nor is intestinal apoC-III responsive to western diet, a significant contrast to hepatic apoC-III stimulation during western diet. These data strongly suggest that intestinal apoC-III is not a FoxO1 target and support the idea that apoC-III is not regulated coordinately with hepatic apoC-III, and establishes another key aspect of apoC-III that is unique in the intestine from the liver. Copyright © 2017 Elsevier Inc. All rights reserved.

O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis

PubMed Central

Zentella, Rodolfo; Hu, Jianhong; Hsieh, Wen-Ping; Matsumoto, Peter A.; Dawdy, Andrew; Barnhill, Benjamin; Oldenhof, Harriëtte; Hartweck, Lynn M.; Maitra, Sushmit; Thomas, Stephen G.; Cockrell, Shelley; Boyce, Michael; Shabanowitz, Jeffrey; Hunt, Donald F.; Olszewski, Neil E.; Sun, Tai-ping

2016-01-01

The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. DELLAs also play a central role in mediating cross-talk between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. However, how these crucial protein–protein interactions can be dynamically regulated during plant development remains unclear. Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors—PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)—that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development. PMID:26773002

Photosynthesis sensitivity to climate change in land surface models

NASA Astrophysics Data System (ADS)

Manrique-Sunen, Andrea; Black, Emily; Verhoef, Anne; Balsamo, Gianpaolo

2016-04-01

Accurate representation of vegetation processes within land surface models is key to reproducing surface carbon, water and energy fluxes. Photosynthesis determines the amount of CO2 fixated by plants as well as the water lost in transpiration through the stomata. Photosynthesis is calculated in land surface models using empirical equations based on plant physiological research. It is assumed that CO2 assimilation is either CO2 -limited, radiation -limited ; and in some models export-limited (the speed at which the products of photosynthesis are used by the plant) . Increased levels of atmospheric CO2 concentration tend to enhance photosynthetic activity, but the effectiveness of this fertilization effect is regulated by environmental conditions and the limiting factor in the photosynthesis reaction. The photosynthesis schemes at the 'leaf level' used by land surface models JULES and CTESSEL have been evaluated against field photosynthesis observations. Also, the response of photosynthesis to radiation, atmospheric CO2 and temperature has been analysed for each model, as this is key to understanding the vegetation response that climate models using these schemes are able to reproduce. Particular emphasis is put on the limiting factor as conditions vary. It is found that while at present day CO2 concentrations export-limitation is only relevant at low temperatures, as CO2 levels rise it becomes an increasingly important restriction on photosynthesis.

Research on key factors and their interaction effects of electromagnetic force of high-speed solenoid valve.

PubMed

Liu, Peng; Fan, Liyun; Hayat, Qaisar; Xu, De; Ma, Xiuzhen; Song, Enzhe

2014-01-01

Analysis consisting of numerical simulations along with lab experiments of interaction effects between key parameters on the electromagnetic force based on response surface methodology (RSM) has been also proposed to optimize the design of high-speed solenoid valve (HSV) and improve its performance. Numerical simulation model of HSV has been developed in Ansoft Maxwell environment and its accuracy has been validated through lab experiments. Effect of change of core structure, coil structure, armature structure, working air gap, and drive current on the electromagnetic force of HSV has been analyzed through simulation model and influence rules of various parameters on the electromagnetic force have been established. The response surface model of the electromagnetic force has been utilized to analyze the interaction effect between major parameters. It has been concluded that six interaction factors including working air gap with armature radius, drive current with armature thickness, coil turns with side pole radius, armature thickness with its radius, armature thickness with side pole radius, and armature radius with side pole radius have significant influence on the electromagnetic force. Optimal match values between coil turns and side pole radius; armature thickness and side pole radius; and armature radius and side pole radius have also been determined.

Research on Key Factors and Their Interaction Effects of Electromagnetic Force of High-Speed Solenoid Valve

PubMed Central

Fan, Liyun; Xu, De; Ma, Xiuzhen; Song, Enzhe

2014-01-01

Analysis consisting of numerical simulations along with lab experiments of interaction effects between key parameters on the electromagnetic force based on response surface methodology (RSM) has been also proposed to optimize the design of high-speed solenoid valve (HSV) and improve its performance. Numerical simulation model of HSV has been developed in Ansoft Maxwell environment and its accuracy has been validated through lab experiments. Effect of change of core structure, coil structure, armature structure, working air gap, and drive current on the electromagnetic force of HSV has been analyzed through simulation model and influence rules of various parameters on the electromagnetic force have been established. The response surface model of the electromagnetic force has been utilized to analyze the interaction effect between major parameters. It has been concluded that six interaction factors including working air gap with armature radius, drive current with armature thickness, coil turns with side pole radius, armature thickness with its radius, armature thickness with side pole radius, and armature radius with side pole radius have significant influence on the electromagnetic force. Optimal match values between coil turns and side pole radius; armature thickness and side pole radius; and armature radius and side pole radius have also been determined. PMID:25243217

O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis.

PubMed

Zentella, Rodolfo; Hu, Jianhong; Hsieh, Wen-Ping; Matsumoto, Peter A; Dawdy, Andrew; Barnhill, Benjamin; Oldenhof, Harriëtte; Hartweck, Lynn M; Maitra, Sushmit; Thomas, Stephen G; Cockrell, Shelley; Boyce, Michael; Shabanowitz, Jeffrey; Hunt, Donald F; Olszewski, Neil E; Sun, Tai-Ping

2016-01-15

The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. DELLAs also play a central role in mediating cross-talk between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. However, how these crucial protein-protein interactions can be dynamically regulated during plant development remains unclear. Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development. © 2016 Zentella et al.; Published by Cold Spring Harbor Laboratory Press.

Redox Stimulation of Human THP-1 Monocytes in Response to Cold Physical Plasma.

PubMed

Bekeschus, Sander; Schmidt, Anke; Bethge, Lydia; Masur, Kai; von Woedtke, Thomas; Hasse, Sybille; Wende, Kristian

2016-01-01

In plasma medicine, cold physical plasma delivers a delicate mixture of reactive components to cells and tissues. Recent studies suggested a beneficial role of cold plasma in wound healing. Yet, the biological processes related to the redox modulation via plasma are not fully understood. We here used the monocytic cell line THP-1 as a model to test their response to cold plasma in vitro. Intriguingly, short term plasma treatment stimulated cell growth. Longer exposure only modestly compromised cell viability but apparently supported the growth of cells that were enlarged in size and that showed enhanced metabolic activity. A significantly increased mitochondrial content in plasma treated cells supported this notion. On THP-1 cell proteome level, we identified an increase of protein translation with key regulatory proteins being involved in redox regulation (hypoxia inducible factor 2α), differentiation (retinoic acid signaling and interferon inducible factors), and cell growth (Yin Yang 1). Regulation of inflammation is a key element in many chronic diseases, and we found a significantly increased expression of the anti-inflammatory heme oxygenase 1 (HMOX1) and of the neutrophil attractant chemokine interleukin-8 (IL-8). Together, these results foster the view that cold physical plasma modulates the redox balance and inflammatory processes in wound related cells.

CPSF30 at the Interface of Alternative Polyadenylation and Cellular Signaling in Plants

PubMed Central

Chakrabarti, Manohar; Hunt, Arthur G.

2015-01-01

Post-transcriptional processing, involving cleavage of precursor messenger RNA (pre mRNA), and further incorporation of poly(A) tail to the 3' end is a key step in the expression of genetic information. Alternative polyadenylation (APA) serves as an important check point for the regulation of gene expression. Recent studies have shown widespread prevalence of APA in diverse systems. A considerable amount of research has been done in characterizing different subunits of so-called Cleavage and Polyadenylation Specificity Factor (CPSF). In plants, CPSF30, an ortholog of the 30 kD subunit of mammalian CPSF is a key polyadenylation factor. CPSF30 in the model plant Arabidopsis thaliana was reported to possess unique biochemical properties. It was also demonstrated that poly(A) site choice in a vast majority of genes in Arabidopsis are CPSF30 dependent, suggesting a pivotal role of this gene in APA and subsequent regulation of gene expression. There are also indications of this gene being involved in oxidative stress and defense responses and in cellular signaling, suggesting a role of CPSF30 in connecting physiological processes and APA. This review will summarize the biochemical features of CPSF30, its role in regulating APA, and possible links with cellular signaling and stress response modules. PMID:26061761

Examining the intersection of sex and stress in modelling neuropsychiatric disorders.

PubMed

Goel, N; Bale, T L

2009-03-01

Sex-biased neuropsychiatric disorders, including major depressive disorder and schizophrenia, are the major cause of disability in the developed world. Elevated stress sensitivity has been proposed as a key underlying factor in disease onset. Sex differences in stress sensitivity are associated with corticotrophin-releasing factor (CRF) and serotonin neurotransmission, which are important central regulators of mood and coping responses. To elucidate the underlying neurobiology of stress-related disease predisposition, it is critical to develop appropriate animal models of stress pathway dysregulation. Furthermore, the inclusion of sex difference comparisons in stress responsive behaviours, physiology and central stress pathway maturation in these models is essential. Recent studies by our laboratory and others have begun to investigate the intersection of stress and sex where the development of mouse models of stress pathway dysregulation via prenatal stress experience or early-life manipulations has provided insight into points of developmental vulnerability. In addition, examination of the maturation of these pathways, including the functional importance of the organisational and activational effects of gonadal hormones on stress responsivity, is essential for determination of when sex differences in stress sensitivity may begin. In such studies, we have detected distinct sex differences in stress coping strategies where activational effects of testosterone produced females that displayed male-like strategies in tests of passive coping, but were similar to females in tests of active coping. In a second model of elevated stress sensitivity, male mice experiencing prenatal stress early in gestation showed feminised physiological and behavioural stress responses, and were highly sensitive to a low dose of selective serotonin reuptake inhibitors. Analyses of expression and epigenetic patterns revealed changes in CRF and glucocorticoid receptor genes in these mice. Mechanistically, stress early in pregnancy produced a significant sex-dependent effect on placental gene expression that was supportive of altered foetal transport of key growth factors and nutrients. These mouse models examining alterations and hormonal effects on development of stress pathways provide necessary insight into how specific stress responses can be reprogrammed early in development resulting in sex differences in stress sensitivity and neuropsychiatric disease vulnerability.

SAPFLUXNET: towards a global database of sap flow measurements.

PubMed

Poyatos, Rafael; Granda, Víctor; Molowny-Horas, Roberto; Mencuccini, Maurizio; Steppe, Kathy; Martínez-Vilalta, Jordi

2016-12-01

Plant transpiration is the main evaporative flux from terrestrial ecosystems; it controls land surface energy balance, determines catchment hydrological responses and influences regional and global climate. Transpiration regulation by plants is a key (and still not completely understood) process that underlies vegetation drought responses and land evaporative fluxes under global change scenarios. Thermometric methods of sap flow measurement have now been widely used to quantify whole-plant and stand transpiration in forests, shrublands and orchards around the world. A large body of research has applied sap flow methods to analyse seasonal and diurnal patterns of transpiration and to quantify their responses to hydroclimatic variability, but syntheses of sap flow data at regional to global scales are extremely rare. Here we present the SAPFLUXNET initiative, aimed at building the first global database of plant-level sap flow measurements. A preliminary metadata survey launched in December 2015 showed an encouraging response by the sap flow community, with sap flow data sets from field studies representing >160 species and >120 globally distributed sites. The main goal of SAPFLUXNET is to analyse the ecological factors driving plant- and stand-level transpiration. SAPFLUXNET will open promising research avenues at an unprecedented global scope, namely: (i) exploring the spatio-temporal variability of plant transpiration and its relationship with plant and stand attributes, (ii) summarizing physiological regulation of transpiration by means of few water-use traits, usable for land surface models, (iii) improving our understanding of the coordination between gas exchange and plant-level traits (e.g., hydraulics) and (iv) analysing the ecological factors controlling stand transpiration and evapotranspiration partitioning. Finally, SAPFLUXNET can provide a benchmark to test models of physiological controls of transpiration, contributing to improve the accuracy of individual water stress responses, a key element to obtain robust predictions of vegetation responses to climate change. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

School Gardens: A Qualitative Study on Implementation Practices.

PubMed

Huys, Nele; De Cocker, Katrien; De Craemer, Marieke; Roesbeke, Marleen; Cardon, Greet; De Lepeleere, Sara

2017-11-25

School gardens have beneficial effects on children's dietary behaviors but information on its implementation is scarce. The current study aimed to gain insight in implementation practices of school gardens and in perceptions of key members and children towards a school garden. We conducted twelve interviews involving 14 key members and five focus groups with 38 children from fifth to sixth grade (10-13 years old) in four primary schools in Ghent (Flanders, Belgium). We analyzed the interviews and focus groups in NVivo, using thematic analysis. School gardens were mainly initiated to involve children in nature, not to improve vegetable consumption. Participants were positive about having a school garden, experienced facilitating factors (e.g., adaptability of the garden, having a person responsible for the garden), but also various barriers (e.g., difficulties with startup, maintenance during summer holidays and integration in the school curriculum) and suggested some solutions (e.g., involving external organizations and parents, expanding the garden) and motivating factors for children (e.g., colorful plants, use of gloves). In order to improve implementation and to contribute to children's health, future school gardening projects should take the recommendations of key members and children into account.

School Gardens: A Qualitative Study on Implementation Practices

PubMed Central

De Cocker, Katrien; Roesbeke, Marleen; De Lepeleere, Sara

2017-01-01

School gardens have beneficial effects on children’s dietary behaviors but information on its implementation is scarce. The current study aimed to gain insight in implementation practices of school gardens and in perceptions of key members and children towards a school garden. We conducted twelve interviews involving 14 key members and five focus groups with 38 children from fifth to sixth grade (10–13 years old) in four primary schools in Ghent (Flanders, Belgium). We analyzed the interviews and focus groups in NVivo, using thematic analysis. School gardens were mainly initiated to involve children in nature, not to improve vegetable consumption. Participants were positive about having a school garden, experienced facilitating factors (e.g., adaptability of the garden, having a person responsible for the garden), but also various barriers (e.g., difficulties with startup, maintenance during summer holidays and integration in the school curriculum) and suggested some solutions (e.g., involving external organizations and parents, expanding the garden) and motivating factors for children (e.g., colorful plants, use of gloves). In order to improve implementation and to contribute to children’s health, future school gardening projects should take the recommendations of key members and children into account. PMID:29186835

An ignition key for atomic-scale engines

NASA Astrophysics Data System (ADS)

Dundas, Daniel; Cunningham, Brian; Buchanan, Claire; Terasawa, Asako; Paxton, Anthony T.; Todorov, Tchavdar N.

2012-10-01

A current-carrying resonant nanoscale device, simulated by non-adiabatic molecular dynamics, exhibits sharp activation of non-conservative current-induced forces with bias. The result, above the critical bias, is generalized rotational atomic motion with a large gain in kinetic energy. The activation exploits sharp features in the electronic structure, and constitutes, in effect, an ignition key for atomic-scale motors. A controlling factor for the effect is the non-equilibrium dynamical response matrix for small-amplitude atomic motion under current. This matrix can be found from the steady-state electronic structure by a simpler static calculation, providing a way to detect the likely appearance, or otherwise, of non-conservative dynamics, in advance of real-time modelling.

The host immune response to Clostridium difficile infection

PubMed Central

2013-01-01

Clostridium difficile infection (CDI) is the most common infectious cause of healthcare-acquired diarrhoea. Outcomes of C. difficile colonization are varied, from asymptomatic carriage to fulminant colitis and death, due in part to the interplay between the pathogenic virulence factors of the bacterium and the counteractive immune responses of the host. Secreted toxins A and B are the major virulence factors of C. difficile and induce a profound inflammatory response by intoxicating intestinal epithelial cells causing proinflammatory cytokine release. Host cell necrosis, vascular permeability and neutrophil infiltration lead to an elevated white cell count, profuse diarrhoea and in severe cases, dehydration, hypoalbuminaemia and toxic megacolon. Other bacterial virulence factors, including surface layer proteins and flagella proteins, are detected by host cell surface signal molecules that trigger downstream cell-mediated immune pathways. Human studies have identified a role for serum and faecal immunoglobulin levels in protection from disease, but the recent development of a mouse model of CDI has enabled studies into the precise molecular interactions that trigger the immune response during infection. Key effector molecules have been identified that can drive towards a protective anti-inflammatory response or a damaging proinflammatory response. The limitations of current antimicrobial therapies for CDI have led to the development of both active and passive immunotherapies, none of which have, as yet been formally approved for CDI. However, recent advances in our understanding of the molecular basis of host immune protection against CDI may provide an exciting opportunity for novel therapeutic developments in the future. PMID:25165542

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.

Role of Nuclear Factor Erythroid 2-Related Factor 2 in Diabetic Nephropathy

PubMed Central

Min, Xu; Xu, Xiaohong

2017-01-01

Diabetic nephropathy (DN) is manifested as increased urinary protein level, decreased glomerular filtration rate, and final renal dysfunction. DN is the leading cause of end-stage renal disease worldwide and causes a huge societal healthcare burden. Since satisfied treatments are still limited, exploring new strategies for the treatment of this disease is urgently needed. Oxidative stress takes part in the initiation and development of DN. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in the cellular response to oxidative stress. Thus, activation of Nrf2 seems to be a new choice for the treatment of DN. In current review, we discussed and summarized the therapeutic effects of Nrf2 activation on DN from both basic and clinical studies. PMID:28512642

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 matrix degrading and anabolic matrix regenerating activities.

Creation and the empirical validation of the dignity card-sort tool to assess factors influencing erosion of dignity at life's end.

PubMed

Periyakoil, Vyjeyanthi S; Kraemer, Helena Chmura; Noda, Arthur

2009-12-01

Patients often experience erosion of dignity as they cope with the dying process. Preserving patient dignity is a sentinel premise of palliative care. This study was conducted to gain a better understanding of factors influencing erosion of dignity at the end of life. We conducted an open-ended written survey of 100 multidisciplinary providers (69% response rate) and responses were categorized to identify 18 themes that were used to create a card-sort tool. The initial 18-item tool was administered to nurses (n = 83), nonhospice community-dwelling subjects (n = 190) and hospice patients (n = 26) and a principal component analysis (PCA) was used to identify the 6 primary factors. The key item in each factor as identified by the PCA was used to create the final 6-item dignity card-sort tool (DCT). The DCT was also administered to physicians caring for palliative care patients (n = 21). For each of the final 6 items, the correlation between the respondents (nurses, physicians, nonterminally ill subjects, and subjects receiving hospice care) was calculated using the Spearman's correlation coefficient. The nurses were very highly positively correlated with the physicians (correlation coefficient = 0.94) and the community-dwelling nonterminally ill subjects were highly positively correlated with the subjects receiving hospice care (correlation coefficient = 0.67). More importantly, both the nurses and physicians were negatively correlated with both community dwelling nonterminally ill subjects and the subjects receiving hospice care. The health professionals in the study felt that treating a patient with disrespect and not carrying out their wishes resulted in erosion of dignity. In contrast patients thought that poor medical care and untreated pain were the most important factors leading to erosion of dignity at life's end. The DCT is a promising tool that may help clinicians identify key factors resulting in perceptions of erosion of dignity in adult palliative care patients.

Creation and the Empirical Validation of the Dignity Card-Sort Tool To Assess Factors Influencing Erosion of Dignity at Life's End

PubMed Central

Chmura Kraemer, Helena; Noda, Arthur

2009-01-01

Abstract Patients often experience erosion of dignity as they cope with the dying process. Preserving patient dignity is a sentinel premise of palliative care. This study was conducted to gain a better understanding of factors influencing erosion of dignity at the end of life. We conducted an open-ended written survey of 100 multidisciplinary providers (69% response rate) and responses were categorized to identify 18 themes that were used to create a card-sort tool. The initial 18-item tool was administered to nurses (n = 83), nonhospice community-dwelling subjects (n = 190) and hospice patients (n = 26) and a principal component analysis (PCA) was used to identify the 6 primary factors. The key item in each factor as identified by the PCA was used to create the final 6-item dignity card-sort tool (DCT). The DCT was also administered to physicians caring for palliative care patients (n = 21). For each of the final 6 items, the correlation between the respondents (nurses, physicians, nonterminally ill subjects, and subjects receiving hospice care) was calculated using the Spearman's correlation coefficient. The nurses were very highly positively correlated with the physicians (correlation coefficient = 0.94) and the community-dwelling nonterminally ill subjects were highly positively correlated with the subjects receiving hospice care (correlation coefficient = 0.67). More importantly, both the nurses and physicians were negatively correlated with both community dwelling nonterminally ill subjects and the subjects receiving hospice care. The health professionals in the study felt that treating a patient with disrespect and not carrying out their wishes resulted in erosion of dignity. In contrast patients thought that poor medical care and untreated pain were the most important factors leading to erosion of dignity at life's end. The DCT is a promising tool that may help clinicians identify key factors resulting in perceptions of erosion of dignity in adult palliative care patients. PMID:19708793

Kruppel-like factor 2 inhibits hypoxia-inducible factor 1alpha expression and function in the endothelium.

PubMed

Kawanami, Daiji; Mahabeleshwar, Ganapati H; Lin, Zhiyong; Atkins, G Brandon; Hamik, Anne; Haldar, Saptarsi M; Maemura, Koji; Lamanna, Joseph C; Jain, Mukesh K

2009-07-31

Hypoxia-inducible factor 1 (HIF-1) is a central regulator of the hypoxic response in many cell types. In endothelial cells, HIF-1 induces the expression of key proangiogenic factors to promote angiogenesis. Recent studies have identified Kruppel-like factor 2 (KLF2) as a potent inhibitor of angiogenesis. However, the role of KLF2 in regulating HIF-1 expression and function has not been evaluated. KLF2 expression was induced acutely by hypoxia in endothelial cells. Adenoviral overexpression of KLF2 inhibited hypoxia-induced expression of HIF-1alpha and its target genes such as interleukin 8, angiopoietin-2, and vascular endothelial growth factor in endothelial cells. Conversely, knockdown of KLF2 increased expression of HIF-1alpha and its targets. Furthermore, KLF2 inhibited hypoxia-induced endothelial tube formation, whereas endothelial cells from mice with haploinsufficiency of KLF2 showed increased tube formation in response to hypoxia. Consistent with this ex vivo observation, KLF2 heterozygous mice showed increased microvessel density in the brain. Mechanistically, KLF2 promoted HIF-1alpha degradation in a von Hippel-Lindau protein-independent but proteasome-dependent manner. Finally, KLF2 disrupted the interaction between HIF-1alpha and its chaperone Hsp90, suggesting that KLF2 promotes degradation of HIF-1alpha by affecting its folding and maturation. These observations identify KLF2 as a novel inhibitor of HIF-1alpha expression and function. Therefore, KLF2 may be a target for modulating the angiogenic response in disease states.

Liver-derived systemic factors drive β-cell hyperplasia in insulin resistant states

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

El Ouaamari, Abdelfattah; Kawamori, Dan; Dirice, Ercument

2013-02-21

Integrative organ cross-talk regulates key aspects of energy homeostasis and its dysregulation may underlie metabolic disorders such as obesity and diabetes. To test the hypothesis that cross-talk between the liver and pancreatic islets modulates β-cell growth in response to insulin resistance, we used the Liver-specific Insulin Receptor Knockout (LIRKO) mouse, a unique model that exhibits dramatic islet hyperplasia. Using complementary in vivo parabiosis and transplantation assays, and in vitro islet culture approaches, we demonstrate that humoral, non-neural, non-cell autonomous factor(s) induce β-cell proliferation in LIRKO mice. Furthermore, we report that a hepatocyte-derived factor(s) stimulates mouse and human β-cell proliferation inmore » ex vivo assays, independent of ambient glucose and insulin levels. These data implicate the liver as a critical source of β-cell growth factors in insulin resistant states.« less

Obesity and Cancer Metabolism: A Perspective on Interacting Tumor-Intrinsic and Extrinsic Factors.

PubMed

Doerstling, Steven S; O'Flanagan, Ciara H; Hursting, Stephen D

2017-01-01

Obesity is associated with increased risk and poor prognosis of many types of cancers. Several obesity-related host factors involved in systemic metabolism can influence tumor initiation, progression, and/or response to therapy, and these have been implicated as key contributors to the complex effects of obesity on cancer incidence and outcomes. Such host factors include systemic metabolic regulators including insulin, insulin-like growth factor 1, adipokines, inflammation-related molecules, and steroid hormones, as well as the cellular and structural components of the tumor microenvironment, particularly adipose tissue. These secreted and structural host factors are extrinsic to, and interact with, the intrinsic metabolic characteristics of cancer cells to influence their growth and spread. This review will focus on the interplay of these tumor cell-intrinsic and extrinsic factors in the context of energy balance, with the objective of identifying new intervention targets for preventing obesity-associated cancer.

Fixed-ratio discrimination: effects of response-produced blackouts1

PubMed Central

Lydersen, Tore; Crossman, E. K.

1974-01-01

For three pigeons, reinforcement depended upon a left side-key response after execution of a fixed ratio 10 on the center key, and upon a right side-key response after fixed ratio 20. Each response during the fixed ratios produced a 0.5-sec blackout. The time between the first and last response in fixed ratio 10 was then equated with the time between the first and last response in fixed ratio 20 by increasing the blackout duration. The accuracy of side-key choice was disrupted, thereby suggesting that time, rather than number of responses, controlled choice responding. When the time between the first and last response was equated during both ratios, asymptotic accuracy was approximately equal to (two birds) or somewhat higher than (one bird) that obtained previously. The results of probes with intermediate fixed ratios and blackouts suggested that control of side-key choice had transferred from the time between the first and last response in ratios to blackout duration. PMID:16811819

The nucleosome: orchestrating DNA damage signaling and repair within chromatin.

PubMed

Agarwal, Poonam; Miller, Kyle M

2016-10-01

DNA damage occurs within the chromatin environment, which ultimately participates in regulating DNA damage response (DDR) pathways and repair of the lesion. DNA damage activates a cascade of signaling events that extensively modulates chromatin structure and organization to coordinate DDR factor recruitment to the break and repair, whilst also promoting the maintenance of normal chromatin functions within the damaged region. For example, DDR pathways must avoid conflicts between other DNA-based processes that function within the context of chromatin, including transcription and replication. The molecular mechanisms governing the recognition, target specificity, and recruitment of DDR factors and enzymes to the fundamental repeating unit of chromatin, i.e., the nucleosome, are poorly understood. Here we present our current view of how chromatin recognition by DDR factors is achieved at the level of the nucleosome. Emerging evidence suggests that the nucleosome surface, including the nucleosome acidic patch, promotes the binding and activity of several DNA damage factors on chromatin. Thus, in addition to interactions with damaged DNA and histone modifications, nucleosome recognition by DDR factors plays a key role in orchestrating the requisite chromatin response to maintain both genome and epigenome integrity.

Arabidopsis KANADI1 acts as a transcriptional repressor by interacting with a specific cis-element and regulates auxin biosynthesis, transport, and signaling in opposition to HD-ZIPIII factors.

PubMed

Huang, Tengbo; Harrar, Yaël; Lin, Changfa; Reinhart, Brenda; Newell, Nicole R; Talavera-Rauh, Franklin; Hokin, Samuel A; Barton, M Kathryn; Kerstetter, Randall A

2014-01-01

The formation of leaves and other lateral organs in plants depends on the proper specification of adaxial-abaxial (upper-lower) polarity. KANADI1 (KAN1), a member of the GARP family of transcription factors, is a key regulator of abaxial identity, leaf growth, and meristem formation in Arabidopsis thaliana. Here, we demonstrate that the Myb-like domain in KAN1 binds the 6-bp motif GNATA(A/T) and that this motif alone is sufficient to squelch transcription of a linked reporter in vivo. In addition, we report that KAN1 acts as a transcriptional repressor. Among its targets are genes involved in auxin biosynthesis, auxin transport, and auxin response. Furthermore, we find that the adaxializing HD-ZIPIII transcription factor REVOLUTA has opposing effects on multiple components of the auxin pathway. We hypothesize that HD-ZIPIII and KANADI transcription factors pattern auxin accumulation and responsiveness in the embryo. Specifically, we propose the opposing actions of KANADI and HD-ZIPIII factors on cotyledon formation (KANADI represses and HD-ZIPIII promotes cotyledon formation) occur through their opposing actions on genes acting at multiple steps in the auxin pathway.

Composition and structure of Pinus koraiensis mixed forest respond to spatial climatic changes.

PubMed

Zhang, Jingli; Zhou, Yong; Zhou, Guangsheng; Xiao, Chunwang

2014-01-01

Although some studies have indicated that climate changes can affect Pinus koraiensis mixed forest, the responses of composition and structure of Pinus koraiensis mixed forests to climatic changes are unknown and the key climatic factors controlling the composition and structure of Pinus koraiensis mixed forest are uncertain. Field survey was conducted in the natural Pinus koraiensis mixed forests along a latitudinal gradient and an elevational gradient in Northeast China. In order to build the mathematical models for simulating the relationships of compositional and structural attributes of the Pinus koraiensis mixed forest with climatic and non-climatic factors, stepwise linear regression analyses were performed, incorporating 14 dependent variables and the linear and quadratic components of 9 factors. All the selected new models were computed under the +2°C and +10% precipitation and +4°C and +10% precipitation scenarios. The Max Temperature of Warmest Month, Mean Temperature of Warmest Quarter and Precipitation of Wettest Month were observed to be key climatic factors controlling the stand densities and total basal areas of Pinus koraiensis mixed forest. Increased summer temperatures and precipitations strongly enhanced the stand densities and total basal areas of broadleaf trees but had little effect on Pinus koraiensis under the +2°C and +10% precipitation scenario and +4°C and +10% precipitation scenario. These results show that the Max Temperature of Warmest Month, Mean Temperature of Warmest Quarter and Precipitation of Wettest Month are key climatic factors which shape the composition and structure of Pinus koraiensis mixed forest. Although the Pinus koraiensis would persist, the current forests dominated by Pinus koraiensis in the region would all shift and become broadleaf-dominated forests due to the dramatic increase of broadleaf trees under the future global warming and increased precipitation.

GmSBH1, a homeobox transcription factor gene, relates to growth and development and involves in response to high temperature and humidity stress in soybean.

PubMed

Shu, Yingjie; Tao, Yuan; Wang, Shuang; Huang, Liyan; Yu, Xingwang; Wang, Zhankui; Chen, Ming; Gu, Weihong; Ma, Hao

2015-11-01

GmSBH1 involves in response to high temperature and humidity stress. Homeobox transcription factors are key switches that control plant development processes. Glycine max H1 Sbh1 (GmSBH1) was the first homeobox gene isolated from soybean. In the present study, the full ORF of GmSBH1 was isolated, and the encoded protein was found to be a typical class I KNOX homeobox transcription factor. Subcellular localization and transcriptional activation assays showed that GmSBH1 is a nuclear protein and possesses transcriptional activation activity in the homeodomain. The KNOX1 domain was found to play a clear role in suppressing the transcriptional activation activity of GmSBH1. GmSBH1 showed different expression levels among different soybean tissues and was involved in response to high temperature and humidity (HTH) stress in developing soybean seeds. The overexpression of GmSBH1 in Arabidopsis altered leaf and stoma phenotypes and enhanced seed tolerance to HTH stress. Overall, our results indicated that GmSBH1 is involved in growth, development, and enhances tolerance to pre-harvest seed deterioration caused by HTH stress in soybean.

BDNF — a key transducer of antidepressant effects

PubMed Central

Björkholm, Carl; Monteggia, Lisa M.

2016-01-01

How do antidepressants elicit an antidepressant response? Here, we review accumulating evidence that the neurotrophin brain-derived neurotrophic factor (BDNF) serves as a transducer, acting as the link between the antidepressant drug and the neuroplastic changes that result in the improvement of the depressive symptoms. Over the last decade several studies have consistently highlighted BDNF as a key player in antidepressant action. An increase in hippocampal and cortical expression of BDNF mRNA parallels the antidepressant-like response of conventional antidepressants such as SSRIs. Subsequent studies showed that a single bilateral infusion of BDNF into the ventricles or directly into the hippocampus is sufficient to induce a relatively rapid and sustained antidepressant-like effect. Importantly, the antidepressant-like response to conventional antidepressants is attenuated in mice where the BDNF signaling has been disrupted by genetic manipulations. Low dose ketamine, which has been found to induce a rapid antidepressant effect in patients with treatment-resistant depression, is also dependent on increased BDNF signaling. Ketamine transiently increases BDNF translation in hippocampus, leading to enhanced synaptic plasticity and synaptic strength. Ketamine has been shown to increase BDNF translation by blocking NMDA receptor activity at rest, thereby inhibiting calcium influx and subsequently halting eukaryotic elongation factor 2 (eEF2) kinase leading to a desuppression of protein translation, including BDNF translation. The antidepressant-like response of ketamine is abolished in BDNF and TrkB conditional knockout mice, eEF2 kinase knockout mice, in mice carrying the BDNF met/met allele, and by intra-cortical infusions of BDNF-neutralizing antibodies. In summary, current data suggests that conventional antidepressants and ketamine mediate their antidepressant-like effects by increasing BDNF in forebrain regions, in particular the hippocampus, making BDNF an essential determinant of antidepressant efficacy. PMID:26519901

Analysis of the policymaking process in Burkina Faso's health sector: case studies of the creation of two health system support units.

PubMed

Zida, Andre; Lavis, John N; Sewankambo, Nelson K; Kouyate, Bocar; Moat, Kaelan; Shearer, Jessica

2017-02-13

Burkina Faso has made a number of health system policy decisions to improve performance on health indicators and strengthen responsiveness to health-related challenges. These included the creation of a General Directorate of Health Information and Statistics (DGISS) and a technical unit to coordinate performance-based financing (CT-FBR). We analysed the policymaking processes associated with the establishment of these units, and documented the factors that influenced this process. We used a multiple-case study design based on Kingdon's agenda-setting model to investigate the DGISS and CT-FBR policymaking processes. Data were collected from interviews with key informants (n = 28), published literature, policy documents (including two strategic and 230 action plans), and 55 legal/regulatory texts. Interviews were analysed using thematic qualitative analysis. Data from the documentary analysis were triangulated with the qualitative interview data. Key factors influencing the policymaking processes associated with the two units involved the 'problem' (problem identification), 'policy' (formation of policy proposals), and 'politics' (political climate/change) streams, which came together in a way that resulted in proposals being placed on the decision agenda. A number of problems with Burkina Faso's health information and financing systems were identified. Policy proposals for the DGISS and CT-FBR units were developed in response to these problems, emerging from several sources including development partners. Changes in political and public service administrations (specifically the 2008 appointment of a new Minister of Health and the establishment of a new budget allocation system), with corresponding changes in the actors and interests involved, appeared key in elevating the proposals to the decision agenda. Efforts to improve performance on health indicators and strengthen responsiveness to health-related challenges need focus on the need for a compelling problem, a viable policy, and conducive politics in order to make it to the decision agenda.

Hepatocyte growth factor sensitizes brain tumors to c-MET kinase inhibition

PubMed Central

Zhang, Ying; Farenholtz, Kaitlyn E.; Yang, Yanzhi; Guessous, Fadila; diPierro, Charles G.; Calvert, Valerie S.; Deng, Jianghong; Schiff, David; Xin, Wenjun; Lee, Jae K.; Purow, Benjamin; Christensen, James; Petricoin, Emanuel; Abounader, Roger

2013-01-01

Purpose The receptor tyrosine kinase (RTK) c-MET and its ligand hepatocyte growth factor (HGF) are deregulated and promote malignancy in cancer and brain tumors. Consequently, clinically applicable c-MET inhibitors have been developed. The purpose of this study was to investigate the not well known molecular determinants that predict responsiveness to c-MET inhibitors, and to explore new strategies for improving inhibitor efficacy in brain tumors. Experimental design We investigated the molecular factors and pathway activation signatures that determine sensitivity to c-MET inhibitors in a panel of glioblastoma and medulloblastoma cells, glioblastoma stem cells (GSCs), and established cell line-derived xenografts using functional assays, reverse protein microarrays, and in vivo tumor volume measurements, but validation with animal survival analyses remains to be done. We also explored new approaches for improving the efficacy of the inhibitors in vitro and in vivo. Results We found that HGF co-expression is a key predictor of response to c-MET inhibition among the examined factors, and identified an ERK/JAK/p53 pathway activation signature that differentiates c-MET inhibition in responsive and non-responsive cells. Surprisingly, we also found that short pre-treatment of cells and tumors with exogenous HGF moderately but statistically significantly enhanced the anti-tumor effects of c-MET inhibition. We observed a similar ligand-induced sensitization effect to an EGFR small molecule kinase inhibitor. Conclusions These findings allow the identification of a subset of patients that will be responsive to c-MET inhibition, and propose ligand pre-treatment as a potential new strategy for improving the anti-cancer efficacy of RTK inhibitors. PMID:23386689

The patient centered medical home: mental models and practice culture driving the transformation process.

PubMed

Cronholm, Peter F; Shea, Judy A; Werner, Rachel M; Miller-Day, Michelle; Tufano, Jim; Crabtree, Benjamin F; Gabbay, Robert

2013-09-01

The Patient-Centered Medical Home (PCMH) has become a dominant model of primary care re-design. The PCMH model is a departure from more traditional models of healthcare delivery and requires significant transformation to be realized. To describe factors shaping mental models and practice culture driving the PCMH transformation process in a large multi-payer PCMH demonstration project. Individual interviews were conducted at 17 primary care practices in South Eastern Pennsylvania. A total of 118 individual interviews were conducted with clinicians (N = 47), patient educators (N = 4), office administrators (N = 12), medical assistants (N = 26), front office staff (N = 7), nurses (N = 4), care managers (N = 11), social workers (N = 4), and other stakeholders (N = 3). A multi-disciplinary research team used a grounded theory approach to develop the key constructs describing factors shaping successful practice transformation. Three central themes emerged from the data related to changes in practice culture and mental models necessary for PCMH practice transformation: 1) shifting practice perspectives towards proactive, population-oriented care based in practice-patient partnerships; 2) creating a culture of self-examination; and 3) challenges to developing new roles within the practice through distribution of responsibilities and team-based care. The most tension in shifting the required mental models was displayed between clinician and medical assistant participants, revealing significant barriers towards moving away from clinician-centric care. Key factors driving the PCMH transformation process require shifting mental models at the individual level and culture change at the practice level. Transformation is based upon structural and process changes that support orientation of practice mental models towards perceptions of population health, self-assessment, and the development of shared decision-making. Staff buy-in to the new roles and responsibilities driving PCMH transformation was described as central to making sustainable change at the practice level; however, key barriers related to clinician autonomy appeared to interfere with the formation of team-based care.

Modelling rapid flow response of a tile drained hillslope with explicit representation of preferential flow paths and consideration of equifinal model structures

NASA Astrophysics Data System (ADS)

Klaus, Julian; Zehe, Erwin

2010-05-01

Rapid water flow along spatially connected - often biologically mediated - flow paths of minimum flow resistance is widely acknowledged to play a key role in runoff generation at the hillslope and small catchment scales but also in the transport of solutes like agro chemicals and nutrients in cohesive soils. Especially at tile drained fields site connected vertical flow structures such as worm burrows, roots or shrinkage cracks act as short cuts allowing water flow to bypass the soil matrix. In the present study we propose a spatially explicit approach to represent worm burrows as connected structures of high conductivity and low retention capacity in a 2D physically model. With this approach tile drain discharge and preferential flow patterns in soil observed during the irrigation of a tile drained hillslope in the Weiherbach catchment were modelled. The model parameters derived from measurements and are considered to be uncertain. Given this uncertainty of key factors that organise flow and transport at tile drained sites the main objectives of the present studies are to shed light on the following three questions: 1. Does a simplified approach that explicitly represents worm burrows as continuous flow paths of small flow resistance and low retention properties in a 2D physically model allow successful reproduction of event flow response at a tile drained field site in the Weiherbach catchment? 2. Does the above described uncertainty in key factors cause equifinality i.e. are there several model structural setups that reproduce event flow response in an acceptable manner without compromising our physical understanding of the system? 3. If so, what are the key factors that have to be known at high accuracy to reduce the equifinality of model structures? The issue of equifinality is usually discussed in catchment modelling to indicate that often a large set of conceptual model parameter sets allows acceptable reproduction of the behaviour of the system of interest - in many cases catchment stream flow response. Beven and Binley (1992) suggest that these model structures should be considered to be equally likely to account for predictive uncertainty. In this study we show that the above outline approach allows successful prediction of the tile drain discharge and preferential flow patterns in soil observed during the irrigation of a tile drained hillslope in the Weiherbach catchment flow event. Strikingly we a found a considerable equifinality in the model structural setup, when key parameters such as the area density of worm burrows, their hydraulic conductivity and the conductivity of the tile drains were varied within the ranges of either our measurements or measurements reported in the literature. Thirteen different model setups yielded a normalised time-shifted Nash-Sutcliffe of more than 0.9, which means that more than 90% of the flow variability is explained by the model. Also the flow volumes were in good accordance and timing errors were less or equal than 20 min (which corresponds to two simulation output time steps). It is elaborated that this uncertainty/equifinality could be reduced when more precise data on initial states of the subsurface and on the drainage area of a single drainage tube could be made available. However, such data are currently most difficult to assess even at very well investigated site as the one that is dealt with here. We thus suggest non uniqueness of process based model structures seems thus to be an important factor causing predictive uncertainty at many sites where preferential flow dominates systems response. References Beven, K.J. and Binley, A.M., 1992. The future of distributed models: model calibration and uncertainty prediction, Hydrological Processes, 6, p.279-298.

Lethal cutaneous disease in transgenic mice conditionally expressing type I human T cell leukemia virus Tax.

PubMed

Kwon, Hakju; Ogle, Louise; Benitez, Bobby; Bohuslav, Jan; Montano, Mauricio; Felsher, Dean W; Greene, Warner C

2005-10-21

Type I human T cell leukemia virus (HTLV-I) is etiologically linked with adult T cell leukemia, an aggressive and usually fatal expansion of activated CD4+ T lymphocytes that frequently traffic to skin. T cell transformation induced by HTLV-I involves the action of the 40-kDa viral Tax transactivator protein. Tax both stimulates the HTLV-I long terminal repeat and deregulates the expression of select cellular genes by altering the activity of specific host transcription factors, including cyclic AMP-responsive element-binding protein (CREB)/activating transcription factor, NF-kappaB/Rel, and serum response factor. To study initiating events involved in HTLV-I Tax-induced T cell transformation, we generated "Tet-off" transgenic mice conditionally expressing in a lymphocyte-restricted manner (EmuSR alpha promoter-enhancer) either wild-type Tax or mutant forms of Tax that selectively compromise the NF-kappaB (M22) or CREB/activating transcription factor (M47) activation pathways. Wild-type Tax and M47 Tax-expressing mice, but not M22-Tax expressing mice, developed progressive alopecia, hyperkeratosis, and skin lesions containing profuse activated CD4 T cell infiltrates with evidence of deregulated inflammatory cytokine production. In addition, these animals displayed systemic lymphadenopathy and splenomegaly. These findings suggest that Tax-mediated activation of NF-kappaB plays a key role in the development of this aggressive skin disease that shares several features in common with the skin disease occurring during the preleukemic stage in HTLV-I-infected patients. Of note, this skin disease completely resolved when Tax transgene expression was suppressed by administration of doxycycline, emphasizing the key role played by this viral oncoprotein in the observed pathology.

Clinical and biological predictors of response to electroconvulsive therapy (ECT): a review.

PubMed

Pinna, Martina; Manchia, Mirko; Oppo, Rossana; Scano, Filomena; Pillai, Gianluca; Loche, Anna Paola; Salis, Piergiorgio; Minnai, Gian Paolo

2018-03-16

Electroconvulsive therapy (ECT), developed in the 30's by Bini and Cerletti, remains a key element of the therapeutic armamentarium in psychiatry, particularly for severe and life-threatening psychiatric symptoms. However, despite its well-established clinical efficacy, the prescription of ECT has declined constantly over the years due to concerns over its safety (cognitive side effects) and an increasingly negative public perception. As for other treatments in the field of psychiatry, ECT is well suited to a personalized approach that would increment its efficacy, as well as reducing the impact of side effects. This should be based on the priori identification of sub-populations of patients sharing common clinical and biological features that predict a good response to ECT. In this review we have selectively reviewed the evidence on clinical and biological predictors of ECT response. Clinical features such as an older age, presence of psychotic and melancholic depression, a high severity of suicide behavior, and speed of response, appear to be shared by ECT good responders with depressive symptoms. In mania, a greater severity of the index episode, and a reduction of whole brain cortical blood flow are associated with ECT good response. Biological determinants of ECT response in depressive patients are the presence of pre-treatment hyperconnectivity between key areas of brain circuitry of depression, as well as of reduced glutamine/glutamate levels, particularly in the anterior cingulated cortex (ACC). Furthermore, pre ECT high plasma homovanillic acid (HVA) levels, as well as of tumor necrosis factor (TNF)-α, and low pre-ECT levels of S-100B protein, appear to predict ECT response. Finally, polymorphisms within the genes encoding for the brain-derived neurotrophic factor (BDNF), the dopamine 2 receptor gene (DRD2), the dopamine receptor 3 gene (DRD3), the cathechol-o-methyltransferase (COMT), the serotonin-transporter (5-HTT), the 5-hydroxytryptamine 2A receptor (5-HT 2A ), and the norepinephrine transporter (NET), appear to predict a good response to ECT. The integration of these data in specific treatment algorithm might facilitate a personalized approach in ECT. Copyright © 2016. Published by Elsevier B.V.

Determinants of sustainability in solid waste management - The Gianyar Waste Recovery Project in Indonesia

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

Zurbruegg, Christian, E-mail: zurbrugg@eawag.ch; Gfrerer, Margareth, E-mail: margareth.gfrerer@gmx.net; Ashadi, Henki, E-mail: henki@eng.ui.ac.id

2012-11-15

Highlights: Black-Right-Pointing-Pointer Our assessment tool helps evaluate success factors in solid waste projects. Black-Right-Pointing-Pointer Success of the composting plant in Indonesia is linked to its community integration. Black-Right-Pointing-Pointer Appropriate technology is not a main determining success factor for sustainability. Black-Right-Pointing-Pointer Structured assessment of 'best practices' can enhance replication in other cities. - Abstract: According to most experts, integrated and sustainable solid waste management should not only be given top priority, but must go beyond technical aspects to include various key elements of sustainability to ensure success of any solid waste project. Aside from project sustainable impacts, the overall enabling environmentmore » is the key feature determining performance and success of an integrated and affordable solid waste system. This paper describes a project-specific approach to assess typical success or failure factors. A questionnaire-based assessment method covers issues of: (i) social mobilisation and acceptance (social element), (ii) stakeholder, legal and institutional arrangements comprising roles, responsibilities and management functions (institutional element); (iii) financial and operational requirements, as well as cost recovery mechanisms (economic element). The Gianyar Waste Recovery Project in Bali, Indonesia was analysed using this integrated assessment method. The results clearly identified chief characteristics, key factors to consider when planning country wide replication but also major barriers and obstacles which must be overcome to ensure project sustainability. The Gianyar project consists of a composting unit processing 60 tons of municipal waste per day from 500,000 inhabitants, including manual waste segregation and subsequent composting of the biodegradable organic fraction.« less

Integrative Analysis of DNA Methylation and Gene Expression Data Identifies EPAS1 as a Key Regulator of COPD

PubMed Central

Yoo, Seungyeul; Takikawa, Sachiko; Geraghty, Patrick; Argmann, Carmen; Campbell, Joshua; Lin, Luan; Huang, Tao; Tu, Zhidong; Feronjy, Robert; Spira, Avrum; Schadt, Eric E.; Powell, Charles A.; Zhu, Jun

2015-01-01

Chronic Obstructive Pulmonary Disease (COPD) is a complex disease. Genetic, epigenetic, and environmental factors are known to contribute to COPD risk and disease progression. Therefore we developed a systematic approach to identify key regulators of COPD that integrates genome-wide DNA methylation, gene expression, and phenotype data in lung tissue from COPD and control samples. Our integrative analysis identified 126 key regulators of COPD. We identified EPAS1 as the only key regulator whose downstream genes significantly overlapped with multiple genes sets associated with COPD disease severity. EPAS1 is distinct in comparison with other key regulators in terms of methylation profile and downstream target genes. Genes predicted to be regulated by EPAS1 were enriched for biological processes including signaling, cell communications, and system development. We confirmed that EPAS1 protein levels are lower in human COPD lung tissue compared to non-disease controls and that Epas1 gene expression is reduced in mice chronically exposed to cigarette smoke. As EPAS1 downstream genes were significantly enriched for hypoxia responsive genes in endothelial cells, we tested EPAS1 function in human endothelial cells. EPAS1 knockdown by siRNA in endothelial cells impacted genes that significantly overlapped with EPAS1 downstream genes in lung tissue including hypoxia responsive genes, and genes associated with emphysema severity. Our first integrative analysis of genome-wide DNA methylation and gene expression profiles illustrates that not only does DNA methylation play a ‘causal’ role in the molecular pathophysiology of COPD, but it can be leveraged to directly identify novel key mediators of this pathophysiology. PMID:25569234

Key drivers of airline loyalty.

PubMed

Dolnicar, Sara; Grabler, Klaus; Grün, Bettina; Kulnig, Anna

2011-10-01

This study investigates drivers of airline loyalty. It contributes to the body of knowledge in the area by investigating loyalty for a number of a priori market segments identified by airline management and by using a method which accounts for the multi-step nature of the airline choice process. The study is based on responses from 687 passengers. Results indicate that, at aggregate level, frequent flyer membership, price, the status of being a national carrier and the reputation of the airline as perceived by friends are the variables which best discriminate between travellers loyal to the airline and those who are not. Differences in drivers of airline loyalty for a number of segments were identified. For example, loyalty programs play a key role for business travellers whereas airline loyalty of leisure travellers is difficult to trace back to single factors. For none of the calculated models satisfaction emerged as a key driver of airline loyalty.

Dynamite fishing in Tanzania.

PubMed

Slade, Lorna M; Kalangahe, Baraka

2015-12-30

Fishing using explosives is common in Tanzanian waters; it is considered to be more widely practised now than at any other point in history. Mwambao Coastal Community Network, a Tanzanian NGO carried out a multi-stakeholder consultation in April 2014 initiated through the concern of private investors and tourism operators. Consultations were held with villagers, fisheries officers, government officers, hoteliers, dive operators, fish processors, NGOs and other key individuals, and shed some light on key factors enabling this practice to flourish. Key areas identified for attention include engendering political will at all levels, upholding of the law through a non-corrupt enforcement and judicial system, and defining clear roles and responsibilities for monitoring and surveillance. The work identified other successful initiatives which have tackled this pervasive practice including projects that build local capacity for marine governance, villages that have declared themselves intolerant of blast-fishing, and private-public partnerships for patrol and protection. Copyright © 2015 Elsevier B.V. All rights reserved.

Planning, implementing, and evaluating a program to address the oral health needs of aboriginal children in port augusta, australia.

PubMed

Parker, E J; Misan, G; Shearer, M; Richards, L; Russell, A; Mills, H; Jamieson, L M

2012-01-01

Aboriginal Australian children experience profound oral health disparities relative to their non-Aboriginal counterparts. In response to community concerns regarding Aboriginal child oral health in the regional town of Port Augusta, South Australia, a child dental health service was established within a Community Controlled Aboriginal Health Service. A partnership approach was employed with the key aims of (1) quantifying rates of dental service utilisation, (2) identifying factors influencing participation, and (3) planning and establishing a program for delivery of Aboriginal children's dental services that would increase participation and adapt to community needs. In planning the program, levels of participation were quantified and key issues identified through semistructured interviews. After 3.5 years, the participation rate for dental care among the target population increased from 53 to 70 percent. Key areas were identified to encourage further improvements and ensure sustainability in Aboriginal child oral health in this regional location.

Key drivers of airline loyalty

PubMed Central

Dolnicar, Sara; Grabler, Klaus; Grün, Bettina; Kulnig, Anna

2011-01-01

This study investigates drivers of airline loyalty. It contributes to the body of knowledge in the area by investigating loyalty for a number of a priori market segments identified by airline management and by using a method which accounts for the multi-step nature of the airline choice process. The study is based on responses from 687 passengers. Results indicate that, at aggregate level, frequent flyer membership, price, the status of being a national carrier and the reputation of the airline as perceived by friends are the variables which best discriminate between travellers loyal to the airline and those who are not. Differences in drivers of airline loyalty for a number of segments were identified. For example, loyalty programs play a key role for business travellers whereas airline loyalty of leisure travellers is difficult to trace back to single factors. For none of the calculated models satisfaction emerged as a key driver of airline loyalty. PMID:27064618

Counterproductive Consequences of a Conservative Ideology: Medicaid Expansion and Personal Responsibility Requirements.

PubMed

Baker, Allison M; Hunt, Linda M

2016-07-01

Medicaid expansion, a key part of the Affordable Care Act, has been opposed by conservative politicians despite its fiscal and public health benefits. In response, some Republican-led states have expanded Medicaid with new reforms, including requirements for cost sharing and behavioral incentives, that promote conservative political values tied to an ideology of personal responsibility. We examine this trend using Michigan's Medicaid expansion as a case example. We explore the origins, evidence base, and possible consequences of these reforms. We argue that these reforms prioritize ideology over sound public health knowledge, deflecting attention away from the social, economic, and structural factors that influence the health of the poor, and may ultimately contribute to counterproductive public health and fiscal outcomes.

Functional Roles of p38 Mitogen-Activated Protein Kinase in Macrophage-Mediated Inflammatory Responses

PubMed Central

Yang, Yanyan; Yu, Tao; Sung, Gi-Ho; Yoo, Byong Chul

2014-01-01

Inflammation is a natural host defensive process that is largely regulated by macrophages during the innate immune response. Mitogen-activated protein kinases (MAPKs) are proline-directed serine and threonine protein kinases that regulate many physiological and pathophysiological cell responses. p38 MAPKs are key MAPKs involved in the production of inflammatory mediators, including tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2). p38 MAPK signaling plays an essential role in regulating cellular processes, especially inflammation. In this paper, we summarize the characteristics of p38 signaling in macrophage-mediated inflammation. In addition, we discuss the potential of using inhibitors targeting p38 expression in macrophages to treat inflammatory diseases. PMID:24771982

E2F1 and NF-κB: Key Mediators of Inflammation-associated Cancers and Potential Therapeutic Targets.

PubMed

Huang, Yulin; Chen, Rui; Zhou, Jianwei

2016-01-01

Inflammation is the fundamental protective response; however disordered immuno-response can cause chronic human disease, including cancer. Inflammatory cells and mediators are essential to the tumor microenvironment and dissection of this complex molecular and cellular milieu may elucidate a connection between cancer and inflammation and help to identify potential novel therapeutic targets. Thus, focusing on transcription factor NF-κB and E2F1 in inflammation-associated cancer is urgent. NF-κB activation is prevalent in carcinomas, mainly driven by inflammatory cytokines in the tumor microenvironment. E2F1 is also involved in regulating immune responses. Understanding the crosstalk between the two pathways may contribute to the development of novel anti-cancer drugs.

Research on Simulation Requirements and Business Architecture of Automated Demand Response in Power Sales Side Market Liberalization

NASA Astrophysics Data System (ADS)

Liu, Yiqun; Zhou, Pengcheng; Zeng, Ming; Chen, Songsong

2018-01-01

With the gradual reform of the electricity market, the power sale side liberalization has become the focus of attention as the key task of reform. The open power market provides a good environment for DR (Demand Response). It is of great significance to research the simulation requirements and business architecture of ADR (Automatic Demand Response) in power sale side market liberalization. Firstly, this paper analyzes the simulation requirements of ADR. Secondly, it analyzes the influence factors that the business development of ADR from five aspects after power sale side market liberalization. Finally, Based on ADR technology support system, the business architecture of ADR after power sale side market liberalization is constructed.

On the dynamic nature of response criterion in recognition memory: effects of base rate, awareness, and feedback.

PubMed

Rhodes, Matthew G; Jacoby, Larry L

2007-03-01

The authors examined whether participants can shift their criterion for recognition decisions in response to the probability that an item was previously studied. Participants in 3 experiments were given recognition tests in which the probability that an item was studied was correlated with its location during the test. Results from all 3 experiments indicated that participants' response criteria were sensitive to the probability that an item was previously studied and that shifts in criterion were robust. In addition, awareness of the bases for criterion shifts and feedback on performance were key factors contributing to the observed shifts in decision criteria. These data suggest that decision processes can operate in a dynamic fashion, shifting from item to item.

Response audit of an Internet survey of health care providers and administrators: implications for determination of response rates.

PubMed

Dobrow, Mark J; Orchard, Margo C; Golden, Brian; Holowaty, Eric; Paszat, Lawrence; Brown, Adalsteinn D; Sullivan, Terrence

2008-10-16

Internet survey modalities often compare unfavorably with traditional survey modalities, particularly with respect to response rates. Response to Internet surveys can be affected by the distribution options and response/collection features employed as well as the existence of automated (out-of-office) replies, automated forwarding, server rejection, and organizational or personal spam filters. However, Internet surveys also provide unparalleled opportunities to track study subjects and examine many of the factors influencing the determination of response rates. Tracking data available for Internet surveys provide detailed information and immediate feedback on a significant component of response that other survey modalities cannot match. This paper presents a response audit of a large Internet survey of more than 5000 cancer care providers and administrators in Ontario, Canada. Building upon the CHEcklist for Reporting Results of Internet E-Surveys (CHERRIES), the main objectives of the paper are to (a) assess the impact of a range of factors on the determination of response rates for Internet surveys and (b) recommend steps for improving published descriptions of Internet survey methods. We audited the survey response data, analyzing the factors that affected the numerator and denominator in the ultimate determination of response. We also conducted a sensitivity analysis to account for the inherent uncertainty associated with the impact of some of the factors on the response rates. The survey was initially sent out to 5636 health care providers and administrators. The determination of the numerator was influenced by duplicate/unattached responses and response completeness. The numerator varied from a maximum of 2031 crude (unadjusted) responses to 1849 unique views, 1769 participants, and 1616 complete responses. The determination of the denominator was influenced by forwarding of the invitation email to unknown individuals, server rejections, automated replies, spam filters, and 'opt out' options. Based on these factors, the denominator varied from a minimum of 5106 to a maximum of 5922. Considering the different assumptions for the numerator and the denominator, the sensitivity analysis resulted in a 12.5% variation in the response rate (from minimum of 27.3% to maximum of 39.8%) with a best estimate of 32.8%. Depending on how the numerator and denominator are chosen, the resulting response rates can vary widely. The CHERRIES statement was an important advance in identifying key characteristics of Internet surveys that can influence response rates. This response audit suggests the need to further clarify some of these factors when reporting on Internet surveys for health care providers and administrators, particularly when using commercially available Internet survey packages for specified, rather than convenience, samples.

Release of growth factors and the effect of age, sex, and severity of injury after long bone fracture. A preliminary report.

PubMed

Pountos, Ippokratis; Georgouli, Theodora; Henshaw, Karen; Bird, Howard; Giannoudis, Peter V

2013-02-01

The systemic response after fracture is regulated by a complex mechanism involving numerous growth factors. In this study, we analyzed the kinetics of key growth factors following lower-limb long bone fracture. Human serum was isolated from 15 patients suffering from lower-limb long bone fracture (tibia/femur) requiring surgical fixation. The levels of platelet-derived growth factor (PDGF-BB), vascular edothelial growth factor (VEGF), insulin growth factor-I (IGF-I), and transforming growth factor β1 (TGF-β1) were assayed by colorimetric ELISA at different time points during the first week after fracture. 10 healthy volunteers made up the control group of the study. Serum levels of the growth factors measured were compared to age, sex, and injury severity score. We found that there was a decline in the levels of PDGF-BB, IGF-I and TGF-β1 during the first 3 days after fracture. However, VEGF levels remained unchanged. The levels of all the growth factors studied then increased, with the highest concentrations noted at day 7 after surgery. No correlation was found between circulating levels of growth factors and age, injury severity score (ISS), blood loss, or fluid administration. There are systemic mitogenic and osteogenic signals after fracture. Important growth factors are released into the peripheral circulation, but early after surgery it appears that serum levels of key growth factors fall. By 7 days postoperatively, the levels had increased considerably. Our findings should be considered in cases where autologous serum is used for ex vivo expansion of mesenchymal stem cells. There should be further evaluation of the use of these molecules as biomarkers of bone union.

Two-key concurrent responding: response-reinforcement dependencies and blackouts1

PubMed Central

Herbert, Emily W.

1970-01-01

Two-key concurrent responding was maintained for three pigeons by a single variable-interval 1-minute schedule of reinforcement in conjunction with a random number generator that assigned feeder operations between keys with equal probability. The duration of blackouts was varied between keys when each response initiated a blackout, and grain arranged by the variable-interval schedule was automatically presented after a blackout (Exp. I). In Exp. II every key peck, except for those that produced grain, initiated a blackout, and grain was dependent upon a response following a blackout. For each pigeon in Exp. I and for one pigeon in Exp. II, the relative frequency of responding on a key approximated, i.e., matched, the relative reciprocal of the duration of the blackout interval on that key. In a third experiment, blackouts scheduled on a variable-interval were of equal duration on the two keys. For one key, grain automatically followed each blackout; for the other key, grain was dependent upon a response and never followed a blackout. The relative frequency of responding on the former key, i.e., the delay key, better approximated the negative exponential function obtained by Chung (1965) than the matching function predicted by Chung and Herrnstein (1967). PMID:16811458

Enhanced use of phylogenetic data to inform public health approaches to HIV among MSM

PubMed Central

German, Danielle; Grabowski, Mary Kate; Beyrer, Chris

2017-01-01

The multi-dimensional nature and continued evolution of HIV epidemics among men who have sex with men (MSM) requires innovative intervention approaches. Strategies are needed that recognize the individual, social, and structural factors driving HIV transmission; that can pinpoint networks with heightened transmission risk; and that can help target intervention in real-time. HIV phylogenetics is a rapidly evolving field with strong promise for informing innovative responses to the HIV epidemic among MSM. Currently, HIV phylogenetic insights are providing new understandings of characteristics of HIV epidemics involving MSM, social networks influencing transmission, characteristics of HIV transmission clusters involving MSM, targets for antiretroviral and other prevention strategies, and dynamics of emergent epidemics. Maximizing the potential of HIV phylogenetics for HIV responses among MSM will require attention to key methodological challenges and ethical considerations, as well as resolving key implementation and scientific questions. Enhanced and integrated use of HIV surveillance, socio-behavioral, and phylogenetic data resources are becoming increasingly critical for informing public health approaches to HIV among MSM. PMID:27584826

Key stakeholder perspectives on the development of walkable neighbourhoods

PubMed Central

Clark, Marianne I.; Berry, Tanya R.; Spence, John C.; Nykiforuk, Candace; Carlson, Marie; Blanchard, Christopher

2016-01-01

Evidence supports the link between the built environment and physical activity. This study investigated factors that influence the decisions made by key stakeholders as they relate to neighbourhood development. Seventeen stakeholders including public health and municipal employees (n = 9), city councillors (n = 3), and the private sector (e.g., land developers, food retailers) (n = 5), participated in interviews. Private sector participants considered healthy lifestyle choices (e.g., PA) to be related more to individual choice than did other groups. All groups agreed that consumer behaviour is essential to invoking change but did not agree on who is responsible for invoking change. Common barriers included financial costs, car dependency, and social norms. Facilitators included growing awareness of health and environmental issues and increasing buy-in from governing bodies for innovative neighbourhood development. More work is needed that acknowledges the differences between while integrating the diverse perspectives of those responsible for the planning of neighbourhoods that are conducive for physical activity. PMID:19733495

Environment and host as large-scale controls of ectomycorrhizal fungi.

PubMed

van der Linde, Sietse; Suz, Laura M; Orme, C David L; Cox, Filipa; Andreae, Henning; Asi, Endla; Atkinson, Bonnie; Benham, Sue; Carroll, Christopher; Cools, Nathalie; De Vos, Bruno; Dietrich, Hans-Peter; Eichhorn, Johannes; Gehrmann, Joachim; Grebenc, Tine; Gweon, Hyun S; Hansen, Karin; Jacob, Frank; Kristöfel, Ferdinand; Lech, Paweł; Manninger, Miklós; Martin, Jan; Meesenburg, Henning; Merilä, Päivi; Nicolas, Manuel; Pavlenda, Pavel; Rautio, Pasi; Schaub, Marcus; Schröck, Hans-Werner; Seidling, Walter; Šrámek, Vít; Thimonier, Anne; Thomsen, Iben Margrete; Titeux, Hugues; Vanguelova, Elena; Verstraeten, Arne; Vesterdal, Lars; Waldner, Peter; Wijk, Sture; Zhang, Yuxin; Žlindra, Daniel; Bidartondo, Martin I

2018-06-06

Explaining the large-scale diversity of soil organisms that drive biogeochemical processes-and their responses to environmental change-is critical. However, identifying consistent drivers of belowground diversity and abundance for some soil organisms at large spatial scales remains problematic. Here we investigate a major guild, the ectomycorrhizal fungi, across European forests at a spatial scale and resolution that is-to our knowledge-unprecedented, to explore key biotic and abiotic predictors of ectomycorrhizal diversity and to identify dominant responses and thresholds for change across complex environmental gradients. We show the effect of 38 host, environment, climate and geographical variables on ectomycorrhizal diversity, and define thresholds of community change for key variables. We quantify host specificity and reveal plasticity in functional traits involved in soil foraging across gradients. We conclude that environmental and host factors explain most of the variation in ectomycorrhizal diversity, that the environmental thresholds used as major ecosystem assessment tools need adjustment and that the importance of belowground specificity and plasticity has previously been underappreciated.

LAI is the major cause of divergence in CO2 fertilization effect in land surface models

NASA Astrophysics Data System (ADS)

Li, Q.; Luo, Y.; Lu, X.; Wang, Y.; Huang, X.; Lin, G., Sr.

2017-12-01

Concentration-carbon feedback (β), also called CO2 fertilization effect, is an important feedback between terrestrial ecosystems and atmosphere to alleviate global climate change. However, models participating in C4MIP and CMIP5 predicted diverse CO2 fertilization effects under future CO2 inceasing scenarios. Hence identifing the key processes dominating the divergence of β in land surface models is of significance. We calculated CO2 fertilization effects from leaf level, canopy gross productivity level, net ecosystem productivity level and ecosystem carbon stock level in Community Atmosphere Biosphere Land Exchange (CABLE) model. Our results identified LAI is the key factor dominating the divergence of β among C3 plants in CABLE model. Saturation of the ecosystem productivity to increasing CO2 is not only regulated by leaf-level response, but also the response of LAI to increasing CO2. The greatest variation among C3 plants at ecosystem level suggests that other processes such as different allocation patterns and soil carbon dynamics of various vegetation types are also responsible for the divergence. Our results indicate that processes regarding to LAI need to be better calibrated according to experiments and observations in order to better represent the response of ecosystem productivity to increasing CO2.

Alarm setting for the critically ill patient: a descriptive pilot survey of nurses' perceptions of current practice in an Australian Regional Critical Care Unit.

PubMed

Christensen, Martin; Dodds, Andrew; Sauer, Josh; Watts, Nigel

2014-08-01

The aim of this survey was to assess registered nurse's perceptions of alarm setting and management in an Australian Regional Critical Care Unit. The setting and management of alarms within the critical care environment is one of the key responsibilities of the nurse in this area. However, with up to 99% of alarms potentially being false-positives it is easy for the nurse to become desensitised or fatigued by incessant alarms; in some cases up to 400 per patient per day. Inadvertently ignoring, silencing or disabling alarms can have deleterious implications for the patient and nurse. A total population sample of 48 nursing staff from a 13 bedded ICU/HDU/CCU within regional Australia were asked to participate. A 10 item open-ended and multiple choice questionnaire was distributed to determine their perceptions and attitudes of alarm setting and management within this clinical area. Two key themes were identified from the open-ended questions: attitudes towards inappropriate alarm settings and annoyance at delayed responses to alarms. A significant number of respondents (93%) agreed that alarm fatigue can result in alarm desensitisation and the disabling of alarms, whilst 81% suggested the key factors are those associated with false-positive alarms and inappropriately set alarms. This study contributes to what is known about alarm fatigue, setting and management within a critical care environment. In addition it gives an insight as to what nurses' within a regional context consider the key factors which contribute to alarm fatigue. Clearly nursing burnout and potential patient harm are important considerations for practice especially when confronted with alarm fatigue and desensitisation. Therefore, promoting and maintaining an environment of ongoing intra-professional communication and alarm surveillance are crucial in alleviating these potential problems. Copyright © 2014. Published by Elsevier Ltd.

Transcriptomic and Proteomic Analyses Reveal Key Innate Immune Signatures in the Host Response to the Gastrointestinal Pathogen Campylobacter concisus

PubMed Central

Deshpande, Nandan P.; Man, Si Ming; Burgos-Portugal, Jose A.; Khattak, Faisal A.; Raftery, Mark J.; Wilkins, Marc R.; Mitchell, Hazel M.

2014-01-01

Pathogenic species within the genus Campylobacter are responsible for a considerable burden on global health. Campylobacter concisus is an emergent pathogen that plays a role in acute and chronic gastrointestinal disease. Despite ongoing research on Campylobacter virulence mechanisms, little is known regarding the immunological profile of the host response to Campylobacter infection. In this study, we describe a comprehensive global profile of innate immune responses to C. concisus infection in differentiated THP-1 macrophages infected with an adherent and invasive strain of C. concisus. Using RNA sequencing (RNA-seq), quantitative PCR (qPCR), mass spectrometry, and confocal microscopy, we observed differential expression of pattern recognition receptors and robust upregulation of DNA- and RNA-sensing molecules. In particular, we observed IFI16 inflammasome assembly in C. concisus-infected macrophages. Global profiling of the transcriptome revealed the significant regulation of a total of 8,343 transcripts upon infection with C. concisus, which included the activation of key inflammatory pathways involving CREB1, NF-κB, STAT, and interferon regulatory factor signaling. Thirteen microRNAs and 333 noncoding RNAs were significantly regulated upon infection, including MIR221, which has been associated with colorectal carcinogenesis. This study represents a major advance in our understanding of host recognition and innate immune responses to infection by C. concisus. PMID:25486993

The innate immune response to uropathogenic Escherichia coli involves IL-17A in a murine model of urinary tract infection.

PubMed

Sivick, Kelsey E; Schaller, Matthew A; Smith, Sara N; Mobley, Harry L T

2010-02-15

Uropathogenic Escherichia coli is the causative agent for >80% of uncomplicated urinary tract infections (UTIs). Uropathogenic E. coli strains express a number of virulence and fitness factors that allow successful colonization of the mammalian bladder. To combat this, the host has distinct mechanisms to prevent adherence to the bladder wall and to detect and kill uropathogenic E. coli in the event of colonization. In this study, we investigated the role of IL-17A, an innate-adaptive immunomodulatory cytokine, during UTI using a murine model. Splenocytes isolated from mice infected by the transurethral route robustly expressed IL-17A in response to in vitro stimulation with uropathogenic E. coli Ags. Transcript expression of IL-17A in the bladders of infected mice correlated with a role in the innate immune response to UTI, and gammadelta cells seem to be a key source of IL-17A production. Although IL-17A seems to be dispensable for the generation of a protective response to uropathogenic E. coli, its importance in innate immunity is demonstrated by a defect in acute clearance of uropathogenic E. coli in IL-17A(-/-) mice. This clearance defect is likely a result of deficient cytokine and chemokine transcripts and impaired macrophage and neutrophil influx during infection. These results show that IL-17A is a key mediator for the innate immune response to UTIs.

A multinational report of technical factors on stereotactic body radiotherapy for oligometastases.

PubMed

Redmond, Kristin J; Lo, Simon S; Dagan, Roi; Poon, Ian; Foote, Matthew C; Erler, Darby; Lee, Young; Lohr, Frank; Biswas, Tithi; Ricardi, Umberto; Sahgal, Arjun

2017-05-01

Oligometastatic cancer is being increasingly managed with aggressive local therapy using stereotactic body radiation therapy (SBRT). However, few guidelines exist. We summarize the results of an international survey reviewing technical factors for extracranial SBRT for oligometastatic disease to guide safe management. Seven high-volume centers contributed. Levels of agreement were categorized as strong (6-7 common responses), moderate (4-5), low (2-3) or no agreement. We present the results of a multi-national and multi-institutional survey of technical factors of SBRT for extracranial oligometastases. Key methods including target delineation, prescription doses, normal tissue constraints, imaging and set-up for safe implementation and practice of SBRT for oligometastasis have been identified. This manuscript will serve as a foundation for future clinical evaluations.

Key Factors in Development of Man-Made and Natural Ecosystems

NASA Astrophysics Data System (ADS)

Pechurkin, N. S.

1999-01-01

Key factors of ecosystem functioning are of the same nature for artificial and natural types. An hierarchical approach gives the opportunity for estimation of the quantitative behavior of both individual links and the system as a whole. At the organismic level we can use interactions of studied macroorganisms (man, animal, higher plant) with selected microorganisms as key indicating factors of the organisms immune status. The most informative factor for the population/community level is an age structure of populations and relationships of domination/elimination. The integrated key factors of the ecosystems level are productivity and rates of cycling of the limiting substances. The key factors approach is of great value for growth regulations and monitoring the state of any ecosystem, including the life support system (LSS)-type.

Induction of apoptosis of liver cancer cells by nanosecond pulsed electric fields (nsPEFs).

PubMed

He, Ling; Xiao, Deyou; Feng, Jianguo; Yao, Chenguo; Tang, Liling

2017-02-01

The application of nanosecond pulsed electric fields (nsPEFs) is a novel method to induce the death of cancer cells. NsPEFs could directly function on the cell membrane and activate the apoptosis pathways, then induce apoptosis in various cell lines. However, the nsPEFs-inducing-apoptosis action sites and the exact pathways are not clear now. In this study, nsPEFs were applied to the human liver cancer cells HepG2 with different parameters. By apoptosis assay, morphological observation, detecting the mitochondrial membrane potential (ΔΨ m ), intracellular calcium ion concentration ([Ca 2+ ]i) and the expressions of key apoptosis factors, we demonstrated that nsPEFs could induce the morphology of cell apoptosis, the change in ΔΨ m , [Ca 2+ ]i and the upregulation of some key apoptosis factors, which revealed the responses of liver cancer cells and indicated that cells may undergo apoptosis through the mitochondria-dependent pathway after nsPEFs were applied.

From A Distance: The Psychology Of Killing With Remotely Piloted Aircraft

DTIC Science & Technology

2015-01-01

community. The continuing ethical and moral relativism society uses to place new weapons and methods on the battlefield are in plain view with the MQ-1... cultural , social, moral , and technological sub-categories.44 Cultural distancing is a method most commonly used to dehumanize an enemy, effectively...psychological response, emotional distance retains a key role in the overall process. On Killing states, “Factors such as cultural distance, moral

Genome-wide targeted prediction of ABA responsive genes in rice based on over-represented cis-motif in co-expressed genes.

PubMed

Lenka, Sangram K; Lohia, Bikash; Kumar, Abhay; Chinnusamy, Viswanathan; Bansal, Kailash C

2009-02-01

Abscisic acid (ABA), the popular plant stress hormone, plays a key role in regulation of sub-set of stress responsive genes. These genes respond to ABA through specific transcription factors which bind to cis-regulatory elements present in their promoters. We discovered the ABA Responsive Element (ABRE) core (ACGT) containing CGMCACGTGB motif as over-represented motif among the promoters of ABA responsive co-expressed genes in rice. Targeted gene prediction strategy using this motif led to the identification of 402 protein coding genes potentially regulated by ABA-dependent molecular genetic network. RT-PCR analysis of arbitrarily chosen 45 genes from the predicted 402 genes confirmed 80% accuracy of our prediction. Plant Gene Ontology (GO) analysis of ABA responsive genes showed enrichment of signal transduction and stress related genes among diverse functional categories.

A Model of Consumer Response to Over-the-Counter Drug Advertising: Antecedents and Influencing Factors.

PubMed

Huh, Jisu; Delorme, Denise E; Reid, Leonard N

2016-01-01

Given the importance of over-the-counter (OTC) drugs in the health care marketplace and lack of systematic research on OTC drug advertising (OTCA) effects, this study tested a theory-based, product category-specific OTCA effects model. Structural equation modeling analysis of data for 1 OTC drug category, analgesics, supported the proposed model, explaining the OTCA effect process from key consumer antecedents to ad involvement, from ad involvement to ad attention, from ad attention to cognitive responses, then to affective/evaluative responses, leading to the final behavioral outcome. Several noteworthy patterns also emerged: (a) Product involvement was directly linked to ad attention, rather than exerting an indirect influence through ad involvement; (b) ad attention was significantly related to both cognitive and affective/evaluative responses to different degrees, with stronger links to cognitive responses; and (c) ad-prompted actions were influenced by both ad trust and ad attitude.

Organizational resilience: Sustained institutional effectiveness among smaller, private, non-profit US higher education institutions experiencing organizational decline.

PubMed

Moran, Kenneth A

2016-06-04

Recent changes in the United States (US) economy have radically disrupted revenue generation among many institutions within higher education within the US. Chief among these disruptions has been fallout associated with the financial crisis of 2008-2009, which triggered a change in the US higher education environment from a period of relative munificence to a prolonged period of scarcity. The hardest hit by this disruption have been smaller, less wealthy institutions which tend to lack the necessary reserves to financially weather the economic storm. Interestingly, a review of institutional effectiveness among these institutions revealed that while many are struggling, some institutions have found ways to not only successfully cope with the impact of declining revenue, but have been able to capitalize on the disruption and thrive. Organizational response is an important factor in successfully coping with conditions of organizational decline. The study examined the impacts of organizational response on institutional effectiveness among higher education institutions experiencing organizational decline. The study's research question asked why some US higher educational institutions are more resilient at coping with organizational decline than other institutions operating within the same segment of the higher education sector. More specifically, what role does organizational resilience have in helping smaller, private non-profit institutions cope and remain effective during organizational decline? A total of 141 US smaller, private non-profit higher educational institutions participated in the study; specifically, the study included responses from participant institutions' key administrators. 60-item survey evaluated administrator responses corresponding to organizational response and institutional effectiveness. Factor analysis was used to specify the underlying structures of rigidity response, resilience response, and institutional effectiveness. Multiple regression analysis was used to examine the direct and interaction effects between organizational decline, organizational rigidity response, organizational resilience response, and institutional effectiveness, controlling for age of institution and level of endowment. The study validated previous threat-rigidity response findings that organizational decline alone does not adversely impact institutional effectiveness. The direct effect of Goal-Directed Solution Seeking and Role Dependency organizational resilience factors had a positive, significant correlation with the Student Personal Development institutional effectiveness factor. The interactive effect of Goal-Directed Solution Seeking organizational resilience factor during organizational decline had a positive, significant correlation with the Professional Development and Quality of Faculty institutional effectiveness factor. The interactive effect of Avoidance during organizational decline had a positive, significant correlation with the Faculty and Administrator Employment Satisfaction institutional effectiveness factor. The interactive effect of Diminished Innovation, Morale, and Leader Credibility rigidity response factor and Avoidance organizational resilience factor during organizational decline had a positive, significant correlation with the Professional Development and Quality of Faculty institutional effectiveness factor. Lastly, the interactive effect of Increased Scapegoating of Leaders, Interest group Activities, and Conflict rigidity response factor and Avoidance organizational resilience factor during organizational decline had a positive, significant correlation with the Faculty and Administrator Employment Satisfaction institutional effectiveness factor. Factors of organizational resilience were found to have a positive effect among smaller, private non-profit higher educational institutions associated with this study toward sustaining institutional effectiveness during organizational decline. Specifically, the organizational resilience factors of Goal-Directed Solution Seeking (i.e., mission-driven solutions) and Avoidance (i.e., skepticism toward new ideas) play a significant, collaborative role among smaller, private non-profit higher educational institutions when it comes to sustaining institutional effectiveness during organizational decline.

A qualitative investigation into key cultural factors that support abstinence or responsible drinking amongst some Pacific youth living in New Zealand

PubMed Central

2012-01-01

Background Abstinence and responsible drinking are not typically associated with youth drinking culture. Amongst Pacific youth in New Zealand there are high numbers, compared to the general New Zealand population, who choose not to consume alcohol. The Pacific youth population is made up of several ethnic groups; their ethno-cultural values are largely Polynesian and heavily influenced by the socio-economic realities of living in New Zealand. This paper explores factors that support abstinence or responsible drinking amongst Pacific youth living in Auckland. Methods A qualitative study comprised of a series of ethnically-, age-, and gender-matched semi-structured focus group discussions with 69 Pacific youth, aged 15-25 years from a university and selected high-schools. Participants were purposively sampled. Results Key cultural factors that contributed to whether Pacific youth participants were abstinent or responsible drinkers were: significant experiences within Pacific family environments (e.g. young person directly links their decision about alcohol consumption to a positive or negative role model); awareness of the belief that their actions as children of Pacific parents affects the reputation and standing of their Pacific family and community (e.g. church); awareness of traditional Pacific values of respect, reciprocity and cultural taboos (e.g. male–female socialising); commitment to no-alcohol teachings of church or religious faith; having peer support and experiences that force them to consider negative effects of excessive alcohol consumption; and personal awareness that being part of an (excessive) drinking culture may seriously affect health or impede career aspirations. Conclusions The narratives offered by Pacific young people highlighted three key communities of influence: family (immediate and extended, but especially siblings), peers and church. Young people negotiated through these communities of influence their decisions whether to drink alcohol, drink excessively or not at all. For each young person the way in which those three communities came together to support their decisions depended on the specificities of their lived contexts. Pacific young people live lives that share some things in common with other New Zealand youth and others which are more specific to a Pacific ethnic group, especially in relation to the traditional beliefs of their Pacific parents and community. In the development of alcohol harm reduction strategies seeking active Pacific young person and family compliance, it is these “other ethnic things” that requires careful and more qualitative consideration. PMID:22898366

Sensing Danger: Key to Activating Plant Immunity.

PubMed

Gust, Andrea A; Pruitt, Rory; Nürnberger, Thorsten

2017-09-01

In both plants and animals, defense against pathogens relies on a complex surveillance system for signs of danger. Danger signals may originate from the infectious agent or from the host itself. Immunogenic plant host factors can be roughly divided into two categories: molecules which are passively released upon cell damage ('classical' damage-associated molecular patterns, DAMPs), and peptides which are processed and/or secreted upon infection to modulate the immune response (phytocytokines). We highlight the ongoing challenge to understand how plants sense various danger signals and integrate this information to produce an appropriate immune response to diverse challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cellular and molecular mechanisms for the bone response to mechanical loading

NASA Technical Reports Server (NTRS)

Bloomfield, S. A.

2001-01-01

To define the cellular and molecular mechanisms for the osteogenic response of bone to increased loading, several key steps must be defined: sensing of the mechanical signal by cells in bone, transduction of the mechanical signal to a biochemical one, and transmission of that biochemical signal to effector cells. Osteocytes are likely to serve as sensors of loading, probably via interstitial fluid flow produced during loading. Evidence is presented for the role of integrins, the cell's actin cytoskeleton, G proteins, and various intracellular signaling pathways in transducing that mechanical signal to a biochemical one. Nitric oxide, prostaglandins, and insulin-like growth factors all play important roles in these pathways. There is growing evidence for modulation of these mechanotransduction steps by endocrine factors, particularly parathyroid hormone and estrogen. The efficiency of this process is also impaired in the aged animal, yet what remains undefined is at what step mechanotransduction is affected.

Acute suppression of spontaneous neurotransmission drives synaptic potentiation.

PubMed

Nosyreva, Elena; Szabla, Kristen; Autry, Anita E; Ryazanov, Alexey G; Monteggia, Lisa M; Kavalali, Ege T

2013-04-17

The impact of spontaneous neurotransmission on neuronal plasticity remains poorly understood. Here, we show that acute suppression of spontaneous NMDA receptor-mediated (NMDAR-mediated) neurotransmission potentiates synaptic responses in the CA1 regions of rat and mouse hippocampus. This potentiation requires protein synthesis, brain-derived neurotrophic factor expression, eukaryotic elongation factor-2 kinase function, and increased surface expression of AMPA receptors. Our behavioral studies link this same synaptic signaling pathway to the fast-acting antidepressant responses elicited by ketamine. We also show that selective neurotransmitter depletion from spontaneously recycling vesicles triggers synaptic potentiation via the same pathway as NMDAR blockade, demonstrating that presynaptic impairment of spontaneous release, without manipulation of evoked neurotransmission, is sufficient to elicit postsynaptic plasticity. These findings uncover an unexpectedly dynamic impact of spontaneous glutamate release on synaptic efficacy and provide new insight into a key synaptic substrate for rapid antidepressant action.

The intersection between growth factors, autophagy and ER stress: A new target to treat neurodegenerative diseases?

PubMed

Garcia-Huerta, Paula; Troncoso-Escudero, Paulina; Jerez, Carolina; Hetz, Claudio; Vidal, Rene L

2016-10-15

One of the salient features of most neurodegenerative diseases is the aggregation of specific proteins in the brain. This proteostasis imbalance is proposed as a key event triggering the neurodegenerative cascade. The unfolded protein response (UPR) and autophagy pathways are emerging as critical processes implicated in handling disease-related misfolded proteins. However, in some conditions, perturbations in the buffering capacity of the proteostasis network may be part of the etiology of the disease. Thus, pharmacological or gene therapy strategies to enhance autophagy or UPR responses are becoming an attractive target for disease intervention. Here, we discuss current evidence depicting the complex involvement of autophagy and ER stress in brain diseases. Novel pathways to modulate protein misfolding are discussed including the relation between aging and growth factor signaling. This article is part of a Special Issue entitled SI:Autophagy. Copyright © 2016 Elsevier B.V. All rights reserved.

Key ecological responses to nitrogen are altered by climate ...

EPA Pesticide Factsheets

Here we review the effects of nitrogen and climate (e.g. temperature and precipitation) on four aspects of ecosystem structure and function including hydrologic-coupled nitrogen cycling, carbon cycling, acidification and biodiversity. Ecosystems are simultaneously exposed to multiple stressors; two dominant drivers threatening ecosystems are anthropogenic nitrogen loading and climate change. Evaluating the cumulative effects of these stressors provides a holistic view of ecosystem vulnerability, which would better inform policy decisions aimed to protect the sustainability of ecosystems. Our current knowledge of the cumulative effects of these stressors is growing, but limited. The goal of this paper is to synthesize the state of scientific knowledge on how ecosystems are affected by the interactions of meteorlogic/climatic factors (e.g., temperature and precipitation) and nitrogen addition. Understanding the interactions of meteorlogic/climatic factors and nitrogen will help to inform how current and projected variability may affect ecosystem response.

Molecular regulation of effector and memory T cell differentiation

PubMed Central

Chang, John T; Wherry, E John; Goldrath, Ananda W

2015-01-01

Immunological memory is a cardinal feature of adaptive immunity and an important goal of vaccination strategies. Here we highlight advances in the understanding of the diverse T lymphocyte subsets that provide acute and long-term protection from infection. These include new insights into the transcription factors, and the upstream ‘pioneering’ factors that regulate their accessibility to key sites of gene regulation, as well as metabolic regulators that contribute to the differentiation of effector and memory subsets; ontogeny and defining characteristics of tissue-resident memory lymphocytes; and origins of the remarkable heterogeneity exhibited by activated T cells. Collectively, these findings underscore progress in delineating the underlying pathways that control diversification in T cell responses but also reveal gaps in the knowledge, as well as the challenges that arise in the application of this knowledge to rationally elicit desired T cell responses through vaccination and immunotherapy. PMID:25396352

Utilization of the cellular stress response to sensitize cancer cells to TRAIL-mediated apoptosis.

PubMed

Siegelin, Markus David

2012-08-01

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising death ligand who has received significant attention due to its specific anti-cancer activity. Recently, a number of clinical trials involving either recombinant soluble TRAIL or agonistic death receptor (DR) antibodies have even been initiated. One major caveat in TRAIL-based anti-cancer therapies is that a considerable number of cancer cells are notorious resistant to apoptosis induction by TRAIL. Overcoming this primary or secondary evolved resistance is an utmost important goal of present cancer research. The current literature suggests that TRAIL resistance is mediated by a number of endogenous factors. According to recent research, stress-related transcription factors have acquired a pivotal role in the sensitization of highly resistant cancer cells, for example, pancreatic cancer and glioblastoma cells, to TRAIL-mediated cell death. Out of this transcription factor family, C/EBP-homologous protein (CHOP) is linked to the control of DR-mediated apoptosis by modulation of several apoptotic and anti-apoptotic factors. Stress responses in certain organelles, such as endoplasmic reticulum (ER) and mitochondria, are potent inductors of CHOP expression. This report focuses on the influence of stress responses on endogenous or acquired resistance to extrinsic apoptosis in tumor cells and summarizes recent findings and results. The Medline and ClinicalTrials database with key words were used for this review. A potential novel treatment strategy for highly treatment-resistant tumors is the induction of a cellular stress response in cancer cells. The induction of an organelle-related stress response, such as nuclear, ER and mitochondrial stress, leads to a dramatic sensitization of a broad variety of cancer cells of different tumor entities to the apoptotic ligand, TRAIL. Importantly, non-neoplastic cells are not sensitized to TRAIL-mediated cell death through the unfolded protein response in most instances, suggesting that this treatment is not only of high efficacy, but even more less of unwanted toxicity in patients.

Nfatc1 Is a Functional Transcriptional Factor Mediating Nell-1-Induced Runx3 Upregulation in Chondrocytes.

PubMed

Li, Chenshuang; Zheng, Zhong; Zhang, Xinli; Asatrian, Greg; Chen, Eric; Song, Richard; Culiat, Cymbeline; Ting, Kang; Soo, Chia

2018-01-06

Neural EGFL like 1 (Nell-1) is essential for chondrogenic differentiation, maturation, and regeneration. Our previous studies have demonstrated that Nell-1's pro-chondrogenic activities are predominantly reliant upon runt-related transcription factor 3 (Runx3)-mediated Indian hedgehog (Ihh) signaling. Here, we identify the nuclear factor of activated T-cells 1 (Nfatc1) as the key transcriptional factor mediating the Nell-1 → Runx3 signal transduction in chondrocytes. Using chromatin immunoprecipitation assay, we were able to determine that Nfatc1 binds to the -833--810 region of the Runx3 -promoter in response to Nell-1 treatment. By revealing the Nell-1 → Nfatc1 → Runx3 → Ihh cascade, we demonstrate the involvement of Nfatc1, a nuclear factor of activated T-cells, in chondrogenesis, while providing innovative insights into developing a novel therapeutic strategy for cartilage regeneration and other chondrogenesis-related conditions.

Transcriptome analysis reveals regulatory networks underlying differential susceptibility to Botrytis cinerea in response to nitrogen availability in Solanum lycopersicum

PubMed Central

Vega, Andrea; Canessa, Paulo; Hoppe, Gustavo; Retamal, Ignacio; Moyano, Tomas C.; Canales, Javier; Gutiérrez, Rodrigo A.; Rubilar, Joselyn

2015-01-01

Nitrogen (N) is one of the main limiting nutrients for plant growth and crop yield. It is well documented that changes in nitrate availability, the main N source found in agricultural soils, influences a myriad of developmental programs and processes including the plant defense response. Indeed, many agronomical reports indicate that the plant N nutritional status influences their ability to respond effectively when challenged by different pathogens. However, the molecular mechanisms involved in N-modulation of plant susceptibility to pathogens are poorly characterized. In this work, we show that Solanum lycopersicum defense response to the necrotrophic fungus Botrytis cinerea is affected by plant N availability, with higher susceptibility in nitrate-limiting conditions. Global gene expression responses of tomato against B. cinerea under contrasting nitrate conditions reveals that plant primary metabolism is affected by the fungal infection regardless of N regimes. This result suggests that differential susceptibility to pathogen attack under contrasting N conditions is not only explained by a metabolic alteration. We used a systems biology approach to identify the transcriptional regulatory network implicated in plant response to the fungus infection under contrasting nitrate conditions. Interestingly, hub genes in this network are known key transcription factors involved in ethylene and jasmonic acid signaling. This result positions these hormones as key integrators of nitrate and defense against B. cinerea in tomato plants. Our results provide insights into potential crosstalk mechanisms between necrotrophic defense response and N status in plants. PMID:26583019

Knowledge, Attitudes, and Practices Related to Meningitis in Northern Ghana

PubMed Central

Hayden, Mary H.; Dalaba, Maxwell; Awine, Timothy; Akweongo, Patricia; Nyaaba, Gertrude; Anaseba, Dominic; Pelzman, Jamie; Hodgson, Abraham; Pandya, Rajul

2013-01-01

Meningitis has a significant impact in the Sahel, but the mechanisms for transmission and factors determining a person's vulnerability are not well understood. Our survey examined the knowledge, attitudes, and practices of people in a meningitis-endemic area in the Upper East region of northern Ghana to identify social, economic, and behavioral factors that may contribute to disease transmission and possible interventions that might improve health outcomes. Key results suggest potential interventions in response to the risk posed by migration, especially seasonal migration, a lack of knowledge about early symptoms causing delayed treatment, and a need for further education about the protective benefits of vaccination. PMID:23775016

Hydrologic dynamics and ecosystem structure.

PubMed

Rodríguez-Iturbe, I

2003-01-01

Ecohydrology is the science that studies the mutual interaction between the hydrological cycle and ecosystems. Such an interaction is especially intense in water-controlled ecosystems, where water may be a limiting factor, not only because of its scarcity, but also because of its intermittent and unpredictable appearance. Hydrologic dynamics is shown to be a crucial factor for ecological patterns and processes. The probabilistic structure of soil moisture in time and space is presented as the key linkage between soil, climate and vegetation dynamics. Nutrient cycles, vegetation coexistence and plant response to environmental conditions are all intimately linked to the stochastic fluctuation of the hydrologic inputs driving an ecosystem.

Diet, Microbiome, and the Intestinal Epithelium: An Essential Triumvirate?

PubMed Central

Guzman, Javier Rivera; Conlin, Victoria Susan; Jobin, Christian

2013-01-01

The intestinal epithelium represents a critical barrier protecting the host against diverse luminal noxious agents, as well as preventing the uncontrolled uptake of bacteria that could activate an immune response in a susceptible host. The epithelial monolayer that constitutes this barrier is regulated by a meshwork of proteins that orchestrate complex biological function such as permeability, transepithelial electrical resistance, and movement of various macromolecules. Because of its key role in maintaining host homeostasis, factors regulating barrier function have attracted sustained attention from the research community. This paper will address the role of bacteria, bacterial-derived metabolism, and the interplay of dietary factors in controlling intestinal barrier function. PMID:23586037

Interferon regulatory factor 5-dependent immune responses in the draining lymph node protect against West Nile virus infection.

PubMed

Thackray, Larissa B; Shrestha, Bimmi; Richner, Justin M; Miner, Jonathan J; Pinto, Amelia K; Lazear, Helen M; Gale, Michael; Diamond, Michael S

2014-10-01

Upon activation of Toll-like and RIG-I-like receptor signaling pathways, the transcription factor IRF5 translocates to the nucleus and induces antiviral immune programs. The recent discovery of a homozygous mutation in the immunoregulatory gene guanine exchange factor dedicator of cytokinesis 2 (Dock2mu/mu) in several Irf5-/- mouse colonies has complicated interpretation of immune functions previously ascribed to IRF5. To define the antiviral functions of IRF5 in vivo, we infected backcrossed Irf5-/-×Dock2wt/wt mice (here called Irf5-/- mice) and independently generated CMV-Cre Irf5fl/fl mice with West Nile virus (WNV), a pathogenic neurotropic flavivirus. Compared to congenic wild-type animals, Irf5-/- and CMV-Cre Irf5fl/fl mice were more vulnerable to WNV infection, and this phenotype was associated with increased infection in peripheral organs, which resulted in higher virus titers in the central nervous system. The loss of IRF5, however, was associated with only small differences in the type I interferon response systemically and in the draining lymph node during WNV infection. Instead, lower levels of several other proinflammatory cytokines and chemokines, as well as fewer and less activated immune cells, were detected in the draining lymph node 2 days after WNV infection. WNV-specific antibody responses in Irf5-/- mice also were blunted in the context of live or inactivated virus infection and this was associated with fewer antigen-specific memory B cells and long-lived plasma cells. Our results with Irf5-/- mice establish a key role for IRF5 in shaping the early innate immune response in the draining lymph node, which impacts the spread of virus infection, optimal B cell immunity, and disease pathogenesis. Although the roles of IRF3 and IRF7 in orchestrating innate and adaptive immunity after viral infection are established, the function of the related transcription factor IRF5 remains less certain. Prior studies in Irf5-/- mice reported conflicting results as to the contribution of IRF5 in regulating type I interferon and adaptive immune responses. The lack of clarity may stem from a recently discovered homozygous loss-of-function mutation of the immunoregulatory gene Dock2 in several colonies of Irf5-/- mice. Here, using a mouse model with a deficiency in IRF5 and wild-type Dock2 alleles, we investigated how IRF5 modulates West Nile virus (WNV) pathogenesis and host immune responses. Our in vivo studies indicate that IRF5 has a key role in shaping the early proinflammatory cytokine response in the draining lymph node, which impacts immunity and control of WNV infection. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Molecular Signatures of Immunity and Immunogenicity in Infection and Vaccination

PubMed Central

Haks, Mariëlle C.; Bottazzi, Barbara; Cecchinato, Valentina; De Gregorio, Corinne; Del Giudice, Giuseppe; Kaufmann, Stefan H. E.; Lanzavecchia, Antonio; Lewis, David J. M.; Maertzdorf, Jeroen; Mantovani, Alberto; Sallusto, Federica; Sironi, Marina; Uguccioni, Mariagrazia; Ottenhoff, Tom H. M.

2017-01-01

Vaccinology aims to understand what factors drive vaccine-induced immunity and protection. For many vaccines, however, the mechanisms underlying immunity and protection remain incompletely characterized at best, and except for neutralizing antibodies induced by viral vaccines, few correlates of protection exist. Recent omics and systems biology big data platforms have yielded valuable insights in these areas, particularly for viral vaccines, but in the case of more complex vaccines against bacterial infectious diseases, understanding is fragmented and limited. To fill this gap, the EC supported ADITEC project (http://www.aditecproject.eu/; http://stm.sciencemag.org/content/4/128/128cm4.full) featured a work package on “Molecular signatures of immunity and immunogenicity,” aimed to identify key molecular mechanisms of innate and adaptive immunity during effector and memory stages of immune responses following vaccination. Specifically, technologies were developed to assess the human immune response to vaccination and infection at the level of the transcriptomic and proteomic response, T-cell and B-cell memory formation, cellular trafficking, and key molecular pathways of innate immunity, with emphasis on underlying mechanisms of protective immunity. This work intersected with other efforts in the ADITEC project. This review summarizes the main achievements of the work package. PMID:29204145

Type IV secretion system of Brucella spp. and its effectors

PubMed Central

Ke, Yuehua; Wang, Yufei; Li, Wengfeng; Chen, Zeliang

2015-01-01

Brucella spp. are intracellular bacterial pathogens that cause infection in domestic and wild animals. They are often used as model organisms to study intracellular bacterial infections. Brucella VirB T4SS is a key virulence factor that plays important roles in mediating intracellular survival and manipulating host immune response to infection. In this review, we discuss the roles of Brucella VirB T4SS and 15 effectors that are proposed to be crucial for Brucella pathogenesis. VirB T4SS regulates the inflammation response and manipulates vesicle trafficking inside host cells. VirB T4SS also plays crucial roles in the inhibition of the host immune response and intracellular survival during infection. Here, we list the key molecular events in the intracellular life cycle of Brucella that are potentially targeted by the VirB T4SS effectors. Elucidating the functions of these effectors will help clarify the molecular role of T4SS during infection. Furthermore, studying the effectors secreted by Brucella spp. might provide insights into the mechanisms used by the bacteria to hijack the host signaling pathways and aid in the development of better vaccines and therapies against brucellosis. PMID:26528442

Type IV secretion system of Brucella spp. and its effectors.

PubMed

Ke, Yuehua; Wang, Yufei; Li, Wengfeng; Chen, Zeliang

2015-01-01

Brucella spp. are intracellular bacterial pathogens that cause infection in domestic and wild animals. They are often used as model organisms to study intracellular bacterial infections. Brucella VirB T4SS is a key virulence factor that plays important roles in mediating intracellular survival and manipulating host immune response to infection. In this review, we discuss the roles of Brucella VirB T4SS and 15 effectors that are proposed to be crucial for Brucella pathogenesis. VirB T4SS regulates the inflammation response and manipulates vesicle trafficking inside host cells. VirB T4SS also plays crucial roles in the inhibition of the host immune response and intracellular survival during infection. Here, we list the key molecular events in the intracellular life cycle of Brucella that are potentially targeted by the VirB T4SS effectors. Elucidating the functions of these effectors will help clarify the molecular role of T4SS during infection. Furthermore, studying the effectors secreted by Brucella spp. might provide insights into the mechanisms used by the bacteria to hijack the host signaling pathways and aid in the development of better vaccines and therapies against brucellosis.

Integrated RNA-Seq and sRNA-Seq Analysis Identifies Chilling and Freezing Responsive Key Molecular Players and Pathways in Tea Plant (Camellia sinensis)

PubMed Central

Zheng, Chao; Zhao, Lei; Wang, Yu; Shen, Jiazhi; Zhang, Yinfei; Jia, Sisi; Li, Yusheng; Ding, Zhaotang

2015-01-01

Tea [Camellia sinensis (L) O. Kuntze, Theaceae] is one of the most popular non-alcoholic beverages worldwide. Cold stress is one of the most severe abiotic stresses that limit tea plants’ growth, survival and geographical distribution. However, the genetic regulatory network and signaling pathways involved in cold stress responses in tea plants remain unearthed. Using RNA-Seq, DGE and sRNA-Seq technologies, we performed an integrative analysis of miRNA and mRNA expression profiling and their regulatory network of tea plants under chilling (4℃) and freezing (-5℃) stress. Differentially expressed (DE) miRNA and mRNA profiles were obtained based on fold change analysis, miRNAs and target mRNAs were found to show both coherent and incoherent relationships in the regulatory network. Furthermore, we compared several key pathways (e.g., ‘Photosynthesis’), GO terms (e.g., ‘response to karrikin’) and transcriptional factors (TFs, e.g., DREB1b/CBF1) which were identified as involved in the early chilling and/or freezing response of tea plants. Intriguingly, we found that karrikins, a new group of plant growth regulators, and β-primeverosidase (BPR), a key enzyme functionally relevant with the formation of tea aroma might play an important role in both early chilling and freezing response of tea plants. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis further confirmed the results from RNA-Seq and sRNA-Seq analysis. This is the first study to simultaneously profile the expression patterns of both miRNAs and mRNAs on a genome-wide scale to elucidate the molecular mechanisms of early responses of tea plants to cold stress. In addition to gaining a deeper insight into the cold resistant characteristics of tea plants, we provide a good case study to analyse mRNA/miRNA expression and profiling of non-model plant species using next-generation sequencing technology. PMID:25901577

Integrated RNA-Seq and sRNA-Seq Analysis Identifies Chilling and Freezing Responsive Key Molecular Players and Pathways in Tea Plant (Camellia sinensis).

PubMed

Zheng, Chao; Zhao, Lei; Wang, Yu; Shen, Jiazhi; Zhang, Yinfei; Jia, Sisi; Li, Yusheng; Ding, Zhaotang

2015-01-01

Tea [Camellia sinensis (L) O. Kuntze, Theaceae] is one of the most popular non-alcoholic beverages worldwide. Cold stress is one of the most severe abiotic stresses that limit tea plants' growth, survival and geographical distribution. However, the genetic regulatory network and signaling pathways involved in cold stress responses in tea plants remain unearthed. Using RNA-Seq, DGE and sRNA-Seq technologies, we performed an integrative analysis of miRNA and mRNA expression profiling and their regulatory network of tea plants under chilling (4℃) and freezing (-5℃) stress. Differentially expressed (DE) miRNA and mRNA profiles were obtained based on fold change analysis, miRNAs and target mRNAs were found to show both coherent and incoherent relationships in the regulatory network. Furthermore, we compared several key pathways (e.g., 'Photosynthesis'), GO terms (e.g., 'response to karrikin') and transcriptional factors (TFs, e.g., DREB1b/CBF1) which were identified as involved in the early chilling and/or freezing response of tea plants. Intriguingly, we found that karrikins, a new group of plant growth regulators, and β-primeverosidase (BPR), a key enzyme functionally relevant with the formation of tea aroma might play an important role in both early chilling and freezing response of tea plants. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis further confirmed the results from RNA-Seq and sRNA-Seq analysis. This is the first study to simultaneously profile the expression patterns of both miRNAs and mRNAs on a genome-wide scale to elucidate the molecular mechanisms of early responses of tea plants to cold stress. In addition to gaining a deeper insight into the cold resistant characteristics of tea plants, we provide a good case study to analyse mRNA/miRNA expression and profiling of non-model plant species using next-generation sequencing technology.

Autoshaping the pigeon's gape response: acquisition and topography as a function of reinforcer type and magnitude.

PubMed Central

Allan, R W; Zeigler, H P

1994-01-01

The pigeon's key-pecking response is experimentally dissociable into transport (head movement) and gape (jaw movement) components. During conditioning of the key-pecking response, both components come under the control of the conditioned stimulus. To study the acquisition of gape conditioned responses and to clarify the contribution of unconditioned stimulus (reinforcer) variables to the form of the response, gape and key-contact responses were recorded during an autoshaping procedure and reinforcer properties were systematically varied. One group of 8 pigeons was food deprived and subgroups of 2 birds each were exposed to four different pellet sizes as reinforcers, each reinforcer signaled by a keylight conditioned stimulus. A second group was water deprived and received water reinforcers paired with the conditioned stimulus. Water- or food-deprived control groups received appropriate water or food reinforcers that were randomly delivered with respect to the keylight stimulus. Acquisition of the conditioned gape response frequently preceded key-contact responses, and gape conditioned responses were generally elicited at higher rates than were key contacts. The form of the conditioned gape was similar to, but not identical with, the form of the unconditioned gape. The gape component is a critical topographical feature of the conditioned key peck, a sensitive measure of conditioning during autoshaping, and an important source of the observed similarities in the form of conditioned and consummatory responses. PMID:7964365

Autoshaping the pigeon's gape response: acquisition and topography as a function of reinforcer type and magnitude.

PubMed

Allan, R W; Zeigler, H P

1994-09-01

The pigeon's key-pecking response is experimentally dissociable into transport (head movement) and gape (jaw movement) components. During conditioning of the key-pecking response, both components come under the control of the conditioned stimulus. To study the acquisition of gape conditioned responses and to clarify the contribution of unconditioned stimulus (reinforcer) variables to the form of the response, gape and key-contact responses were recorded during an autoshaping procedure and reinforcer properties were systematically varied. One group of 8 pigeons was food deprived and subgroups of 2 birds each were exposed to four different pellet sizes as reinforcers, each reinforcer signaled by a keylight conditioned stimulus. A second group was water deprived and received water reinforcers paired with the conditioned stimulus. Water- or food-deprived control groups received appropriate water or food reinforcers that were randomly delivered with respect to the keylight stimulus. Acquisition of the conditioned gape response frequently preceded key-contact responses, and gape conditioned responses were generally elicited at higher rates than were key contacts. The form of the conditioned gape was similar to, but not identical with, the form of the unconditioned gape. The gape component is a critical topographical feature of the conditioned key peck, a sensitive measure of conditioning during autoshaping, and an important source of the observed similarities in the form of conditioned and consummatory responses.

IL-17A Synergistically Enhances Bile Acid–Induced Inflammation during Obstructive Cholestasis

PubMed Central

O'Brien, Kate M.; Allen, Katryn M.; Rockwell, Cheryl E.; Towery, Keara; Luyendyk, James P.; Copple, Bryan L.

2014-01-01

During obstructive cholestasis, increased concentrations of bile acids activate ERK1/2 in hepatocytes, which up-regulates early growth response factor 1, a key regulator of proinflammatory cytokines, such as macrophage inflammatory protein 2 (MIP-2), which, in turn, exacerbates cholestatic liver injury. Recent studies have indicated that IL-17A contributes to hepatic inflammation during obstructive cholestasis, suggesting that bile acids and IL-17A may interact to regulate hepatic inflammatory responses. We treated mice with an IL-17A neutralizing antibody or control IgG and subjected them to bile duct ligation. Neutralization of IL-17A prevented up-regulation of proinflammatory cytokines, hepatic neutrophil accumulation, and liver injury, indicating an important role for IL-17A in neutrophilic inflammation during cholestasis. Treatment of primary mouse hepatocytes with taurocholic acid (TCA) increased the expression of MIP-2. Co-treatment with IL-17A synergistically enhanced up-regulation of MIP-2 by TCA. In contrast to MIP-2, IL-17A did not affect up-regulation of Egr-1 by TCA, indicating that IL-17A does not affect bile acid–induced activation of signaling pathways upstream of early growth response factor 1. In addition, bile acids increased expression of IL-23, a key regulator of IL-17A production in hepatocytes in vitro and in vivo. Collectively, these data identify bile acids as novel triggers of the IL-23/IL-17A axis and suggest that IL-17A promotes hepatic inflammation during cholestasis by synergistically enhancing bile acid–induced production of proinflammatory cytokines by hepatocytes. PMID:24012680

Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation.

PubMed

Zhang, Guoqi; Yang, Li; Kim, Gab Seok; Ryan, Kieran; Lu, Shulin; O'Donnell, Rebekah K; Spokes, Katherine; Shapiro, Nathan; Aird, William C; Kluk, Michael J; Yano, Kiichiro; Sanchez, Teresa

2013-07-18

The endothelium, as the interface between blood and all tissues, plays a critical role in inflammation. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid, highly abundant in plasma, that potently regulates endothelial responses through interaction with its receptors (S1PRs). Here, we studied the role of S1PR2 in the regulation of the proadhesion and proinflammatory phenotype of the endothelium. By using genetic approaches and a S1PR2-specific antagonist (JTE013), we found that S1PR2 plays a key role in the permeability and inflammatory responses of the vascular endothelium during endotoxemia. Experiments with bone marrow chimeras (S1pr2(+/+) → S1pr2(+/+), S1pr2(+/+) → S1pr2(-/-), and S1pr2(-/-) → S1pr2(+/+)) indicate the critical role of S1PR2 in the stromal compartment, in the regulation of vascular permeability and vascular inflammation. In vitro, JTE013 potently inhibited tumor necrosis factor α-induced endothelial inflammation. Finally, we provide detailed mechanisms on the downstream signaling of S1PR2 in vascular inflammation that include the activation of the stress-activated protein kinase pathway that, together with the Rho-kinase nuclear factor kappa B pathway (NF-kB), are required for S1PR2-mediated endothelial inflammatory responses. Taken together, our data indicate that S1PR2 is a key regulator of the proinflammatory phenotype of the endothelium and identify S1PR2 as a novel therapeutic target for vascular disorders.

Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity

PubMed Central

Görner, Wolfram; Durchschlag, Erich; Martinez-Pastor, Maria Teresa; Estruch, Francisco; Ammerer, Gustav; Hamilton, Barbara; Ruis, Helmut; Schüller, Christoph

1998-01-01

Msn2p and the partially redundant factor Msn4p are key regulators of stress-responsive gene expression in Saccharomyces cerevisiae. They are required for the transcription of a number of genes coding for proteins with stress-protective functions. Both Msn2p and Msn4p are Cys2His2 zinc finger proteins and bind to the stress response element (STRE). In vivo footprinting studies show that the occupation of STREs is enhanced in stressed cells and dependent on the presence of Msn2p and Msn4p. Both factors accumulate in the nucleus under stress conditions, such as heat shock, osmotic stress, carbon-source starvation, and in the presence of ethanol or sorbate. Stress-induced nuclear localization was found to be rapid, reversible, and independent of protein synthesis. Nuclear localization of Msn2p and Msn4p was shown to be correlated inversely to cAMP levels and protein kinase A (PKA) activity. A region with significant homologies shared between Msn2p and Msn4p is sufficient to confer stress-regulated localization to a SV40–NLS–GFP fusion protein. Serine to alanine or aspartate substitutions in a conserved PKA consensus site abolished cAMP-driven nuclear export and cytoplasmic localization in unstressed cells. We propose stress and cAMP-regulated intracellular localization of Msn2p to be a key step in STRE-dependent transcription and in the general stress response. PMID:9472026

Translational coregulation of 5′TOP mRNAs by TIA-1 and TIAR

PubMed Central

Damgaard, Christian Kroun; Lykke-Andersen, Jens

2011-01-01

The response of cells to changes in their environment often requires coregulation of gene networks, but little is known about how this can occur at the post-transcriptional level. An important example of post-transcriptional coregulation is the selective translational regulation in response to growth conditions of mammalian mRNAs that encode protein biosynthesis factors and contain hallmark 5′-terminal oligopyrimidine tracts (5′TOP). However, the responsible trans-factors and the mechanism by which they coregulate 5′TOP mRNAs have remained elusive. Here we identify stress granule-associated TIA-1 and TIAR proteins as key factors in human 5′TOP mRNA regulation, which upon amino acid starvation assemble onto the 5′ end of 5′TOP mRNAs and arrest translation at the initiation step, as evidenced by TIA-1/TIAR-dependent 5′TOP mRNA translation repression, polysome release, and accumulation in stress granules. This requires starvation-mediated activation of the GCN2 (general control nonderepressible 2) kinase and inactivation of the mTOR (mammalian target of rapamycin) signaling pathway. Our findings provide a mechanistic explanation to the long-standing question of how the network of 5′TOP mRNAs are coregulated according to amino acid availability, thereby allowing redirection of limited resources to mount a nutrient deprivation response. This presents a fundamental example of how a group of mRNAs can be translationally coregulated in response to changes in the cellular environment. PMID:21979918

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

CT contrast predicts pancreatic cancer treatment response to verteporfin-based photodynamic therapy

NASA Astrophysics Data System (ADS)

Jermyn, Michael; Davis, Scott C.; Dehghani, Hamid; Huggett, Matthew T.; Hasan, Tayyaba; Pereira, Stephen P.; Bown, Stephen G.; Pogue, Brian W.

2014-04-01

The goal of this study was to determine dominant factors affecting treatment response in pancreatic cancer photodynamic therapy (PDT), based on clinically available information in the VERTPAC-01 trial. This trial investigated the safety and efficacy of verteporfin PDT in 15 patients with locally advanced pancreatic adenocarcinoma. CT scans before and after contrast enhancement from the 15 patients in the VERTPAC-01 trial were used to determine venous-phase blood contrast enhancement and this was correlated with necrotic volume determined from post-treatment CT scans, along with estimation of optical absorption in the pancreas for use in light modeling of the PDT treatment. Energy threshold contours yielded estimates for necrotic volume based on this light modeling. Both contrast-derived venous blood content and necrotic volume from light modeling yielded strong correlations with observed necrotic volume (R2 = 0.85 and 0.91, respectively). These correlations were much stronger than those obtained by correlating energy delivered versus necrotic volume in the VERTPAC-01 study and in retrospective analysis from a prior clinical study. This demonstrates that contrast CT can provide key surrogate dosimetry information to assess treatment response. It also implies that light attenuation is likely the dominant factor in the VERTPAC treatment response, as opposed to other factors such as drug distribution. This study is the first to show that contrast CT provides needed surrogate dosimetry information to predict treatment response in a manner which uses standard-of-care clinical images, rather than invasive dosimetry methods.

A comprehensive probabilistic analysis model of oil pipelines network based on Bayesian network

NASA Astrophysics Data System (ADS)

Zhang, C.; Qin, T. X.; Jiang, B.; Huang, C.

2018-02-01

Oil pipelines network is one of the most important facilities of energy transportation. But oil pipelines network accident may result in serious disasters. Some analysis models for these accidents have been established mainly based on three methods, including event-tree, accident simulation and Bayesian network. Among these methods, Bayesian network is suitable for probabilistic analysis. But not all the important influencing factors are considered and the deployment rule of the factors has not been established. This paper proposed a probabilistic analysis model of oil pipelines network based on Bayesian network. Most of the important influencing factors, including the key environment condition and emergency response are considered in this model. Moreover, the paper also introduces a deployment rule for these factors. The model can be used in probabilistic analysis and sensitive analysis of oil pipelines network accident.

Antidiuretic hormone resistance in the neonatal cortical collecting tubule is mediated in part by elevated phosphodiesterase activity

PubMed Central

Quigley, Raymond; Chakravarty, Sumana; Baum, Michel

2014-01-01

Neonates cannot concentrate their urine to the same degree as adults. One of the key factors in concentrating the urine is the renal collecting duct osmotic water permeability (Pf) response to antidiuretic hormone (ADH). Neonatal cortical collecting ducts have a blunted Pf response to ADH compared with adult tubules (Pf: 119.0 ± 12.5 vs. 260.1 ± 29.5 µm/s, P < 0.05). We found that the phosphodiesterase activity in the neonatal collecting ducts was higher than that in the adult collecting ducts (3,970 ± 510 vs. 2,440 ± 220 cpm·µg tubular protein−1·20 min−1, P < 0.05). After pretreatment of in vitro microperfused tubules with the nonspecific phosphodiesterase inhibitor IBMX (10−6 M in the bath), the Pf response to ADH in neonatal collecting ducts was 271.4 ± 51.7 µm/s, which was identical to that of the adult collecting duct [315.3 ± 31.3 µm/s, P = not significant (NS)]. Rolipram, a specific type IV phosphodiesterase inhibitor, lowered the elevated phosphodiesterase activity in the neonatal tubules to that in the adult tubules (2,460 ± 210 vs. 2,160 ± 230 cpm·µg tubular protein−1·20 min−1, P = NS). Neonatal tubules pretreated with rolipram (10−5 M) in the bath also had a Pf response to ADH that was comparable to that of the adult tubules (258.2 ± 17.0 vs. 271.4 ± 32.6 µm/s, P = NS). Thus the elevated phosphodiesterase activity in the neonatal tubules appears to be due to an increase in type IV phosphodiesterase activity. Hence, one of the key factors in the decreased ability of neonates to concentrate their urine is overactivity of phosphodiesterase in the cortical collecting duct that blunts the neonatal collecting duct Pf response to ADH. PMID:14644747

Negative feedback regulation of ABA biosynthesis in peanut (Arachis hypogaea): a transcription factor complex inhibits AhNCED1 expression during water stress

PubMed Central

Liu, Shuai; Li, Meijuan; Su, Liangchen; Ge, Kui; Li, Limei; Li, Xiaoyun; Liu, Xu; Li, Ling

2016-01-01

Abscisic acid (ABA), a key plant stress-signaling hormone, is produced in response to drought and counteracts the effects of this stress. The accumulation of ABA is controlled by the enzyme 9-cis-epoxycarotenoid dioxygenase (NCED). In Arabidopsis, NCED3 is regulated by a positive feedback mechanism by ABA. In this study in peanut (Arachis hypogaea), we demonstrate that ABA biosynthesis is also controlled by negative feedback regulation, mediated by the inhibitory effect on AhNCED1 transcription of a protein complex between transcription factors AhNAC2 and AhAREB1. AhNCED1 was significantly down-regulated after PEG treatment for 10 h, at which time ABA content reached a peak. A ChIP-qPCR assay confirmed AhAREB1 and AhNAC2 binding to the AhNCED1 promoter in response to ABA. Moreover, the interaction between AhAREB1 and AhNAC2, and a transient expression assay showed that the protein complex could negatively regulate the expression of AhNCED1. The results also demonstrated that AhAREB1 was the key factor in AhNCED1 feedback regulation, while AhNAC2 played a subsidiary role. ABA reduced the rate of AhAREB1 degradation and enhanced both the synthesis and degradation rate of the AhNAC2 protein. In summary, the AhAREB1/AhNAC2 protein complex functions as a negative feedback regulator of drought-induced ABA biosynthesis in peanut. PMID:27892506

Factors influencing the patient with rheumatoid arthritis in their decision to seek podiatry.

PubMed

Blake, A; Mandy, P J; Stew, G

2013-12-01

Despite the level of foot involvement in rheumatoid arthritis (RA), and the literature to support early assessment of foot care needs, local referral of patients to podiatry has been occurring too late to instigate certain preventative interventions. Preliminary fieldwork has highlighted that the primary responsibility for the instigation of this lies with the patient. The present study describes the factors that influence the patient with RA in their decision to self-report foot problems. A case study research strategy was employed. Nine patients attending the outpatient rheumatology department participated in the study and data were gathered through semi-structured interviews. This information was analysed using a framework approach. The key themes derived from the data suggested that there are a variety of factors influencing the patient's decision to self-report foot concerns. Some will act to encourage the action and others will act to oppose it. Other factors can influence the decision either way, depending on the individual patient (psychological state, previous experience, body image changes). In addition, age, gender, and cultural and social aspects are also significant. Due to the multitude of factors influencing the individual's decision to seek help, the patient cannot be given sole responsibility for their foot health if we wish to achieve timely and appropriate podiatry, as recommended in the literature. Responsibility should be three-way; the patient, the members of the rheumatology team and, once in the podiatry service, the podiatrist should maintain this. Copyright © 2013 John Wiley & Sons, Ltd.

Modeling hypertrophic IP3 transients in the cardiac myocyte.

PubMed

Cooling, Michael; Hunter, Peter; Crampin, Edmund J

2007-11-15

Cardiac hypertrophy is a known risk factor for heart disease, and at the cellular level is caused by a complex interaction of signal transduction pathways. The IP3-calcineurin pathway plays an important role in stimulating the transcription factor NFAT which binds to DNA cooperatively with other hypertrophic transcription factors. Using available kinetic data, we construct a mathematical model of the IP3 signal production system after stimulation by a hypertrophic alpha-adrenergic agonist (endothelin-1) in the mouse atrial cardiac myocyte. We use a global sensitivity analysis to identify key controlling parameters with respect to the resultant IP3 transient, including the phosphorylation of cell-membrane receptors, the ligand strength and binding kinetics to precoupled (with G(alpha)GDP) receptor, and the kinetics associated with precoupling the receptors. We show that the kinetics associated with the receptor system contribute to the behavior of the system to a great extent, with precoupled receptors driving the response to extracellular ligand. Finally, by reparameterizing for a second hypertrophic alpha-adrenergic agonist, angiotensin-II, we show that differences in key receptor kinetic and membrane density parameters are sufficient to explain different observed IP3 transients in essentially the same pathway.

Factors affecting the dissipation of pharmaceuticals in freshwater sediments.

PubMed

Al-Khazrajy, Omar S A; Bergström, Ed; Boxall, Alistair B A

2018-03-01

Degradation is one of the key processes governing the impact of pharmaceuticals in the aquatic environment. Most studies on the degradation of pharmaceuticals have focused on soil and sludge, with fewer exploring persistence in aquatic sediments. We investigated the dissipation of 6 pharmaceuticals from different therapeutic classes in a range of sediment types. Dissipation of each pharmaceutical was found to follow first-order exponential decay. Half-lives in the sediments ranged from 9.5 (atenolol) to 78.8 (amitriptyline) d. Under sterile conditions, the persistence of pharmaceuticals was considerably longer. Stepwise multiple linear regression analysis was performed to explore the relationships between half-lives of the pharmaceuticals, sediment physicochemical properties, and sorption coefficients for the compounds. Sediment clay, silt, and organic carbon content and microbial activity were the predominant factors related to the degradation rates of diltiazem, cimetidine, and ranitidine. Regression analysis failed to highlight a key property which may be responsible for observed differences in the degradation of the other pharmaceuticals. The present results suggest that the degradation rate of pharmaceuticals in sediments is determined by different factors and processes and does not exclusively depend on a single sediment parameter. Environ Toxicol Chem 2018;37:829-838. © 2017 SETAC. © 2017 SETAC.

Local Government Capacity to Respond to Environmental Change: Insights from Towns in New York State.

PubMed

Larson, Lincoln R; Lauber, T Bruce; Kay, David L; Cutts, Bethany B

2017-07-01

Local governments attempting to respond to environmental change face an array of challenges. To better understand policy responses and factors influencing local government capacity to respond to environmental change, we studied three environmental issues affecting rural or peri-urban towns in different regions of New York State: climate change in the Adirondacks (n = 63 towns), loss of open space due to residential/commercial development in the Hudson Valley (n = 50), and natural gas development in the Southern Tier (n = 62). Our analysis focused on towns' progression through three key stages of the environmental policy process (issue awareness and salience, common goals and agenda setting, policy development and implementation) and the factors that affect this progression and overall capacity for environmental governance. We found that-when compared to towns addressing open space development and natural gas development-towns confronted with climate change were at a much earlier stage in the policy process and were generally less likely to display the essential resources, social support, and political legitimacy needed for an effective policy response. Social capital cultivated through collaboration and networking was strongly associated with towns' policy response across all regions and could help municipalities overcome omnipresent resource constraints. By comparing and contrasting municipal responses to each issue, this study highlights the processes and factors influencing local government capacity to address a range of environmental changes across diverse management contexts.

Second-order schedules: discrimination of components1

PubMed Central

Squires, Nancy; Norborg, James; Fantino, Edmund

1975-01-01

Pigeons were exposed to a series of second-order schedules in which the completion of a fixed number of fixed-interval components produced food. In Experiment 1, brief (2 sec) stimulus presentations occurred as each fixed-interval component was completed. During the brief-stimulus presentation terminating the last fixed-interval component, a response was required on a second key, the brief-stimulus key, to produce food. Responses on the brief-stimulus key before the last brief-stimulus presentation had no scheduled consequences, but served as a measure of the extent to which the final component was discriminated from preceding components. Whether there were one, two, four, or eight fixed-interval components, responses on the brief-stimulus key occurred during virtually every brief-stimulus presentation. In Experiment 2, an attempt was made to punish unnecessary responses on the brief-stimulus key, i.e., responses on the brief-stimulus key that occurred before the last component. None of the pigeons learned to withhold these responses, even though they produced a 15-sec timeout and loss of primary reinforcement. In Experiment 3, different key colors were associated with each component of a second-order schedule (a chain schedule). In contrast to Experiment 1, brief-stimulus key responses were confined to the last component. It was concluded that pigeons do not discriminate well between components of second-order schedules unless a unique exteroceptive cue is provided for each component. The relative discriminability of the components may account for the observed differences in initial-component response rates between comparable brief-stimulus, tandem, and chain schedules. PMID:16811868

Balancing Immune Protection and Immune Pathology by CD8+ T-Cell Responses to Influenza Infection

PubMed Central

Duan, Susu; Thomas, Paul G.

2016-01-01

Influenza A virus (IAV) is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL)-mediated immunity contributes to the clearance of virus-infected cells, and CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, its cytotoxicity, and the effects of produced proinflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL antiviral immunity from those necessary to restrain CTL-mediated non-specific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity. PMID:26904022

Porcine Tissue-Specific Regulatory Networks Derived from Meta-Analysis of the Transcriptome

PubMed Central

Pérez-Montarelo, Dafne; Hudson, Nicholas J.; Fernández, Ana I.; Ramayo-Caldas, Yuliaxis; Dalrymple, Brian P.; Reverter, Antonio

2012-01-01

The processes that drive tissue identity and differentiation remain unclear for most tissue types. So are the gene networks and transcription factors (TF) responsible for the differential structure and function of each particular tissue, and this is particularly true for non model species with incomplete genomic resources. To better understand the regulation of genes responsible for tissue identity in pigs, we have inferred regulatory networks from a meta-analysis of 20 gene expression studies spanning 480 Porcine Affymetrix chips for 134 experimental conditions on 27 distinct tissues. We developed a mixed-model normalization approach with a covariance structure that accommodated the disparity in the origin of the individual studies, and obtained the normalized expression of 12,320 genes across the 27 tissues. Using this resource, we constructed a network, based on the co-expression patterns of 1,072 TF and 1,232 tissue specific genes. The resulting network is consistent with the known biology of tissue development. Within the network, genes clustered by tissue and tissues clustered by site of embryonic origin. These clusters were significantly enriched for genes annotated in key relevant biological processes and confirm gene functions and interactions from the literature. We implemented a Regulatory Impact Factor (RIF) metric to identify the key regulators in skeletal muscle and tissues from the central nervous systems. The normalization of the meta-analysis, the inference of the gene co-expression network and the RIF metric, operated synergistically towards a successful search for tissue-specific regulators. Novel among these findings are evidence suggesting a novel key role of ERCC3 as a muscle regulator. Together, our results recapitulate the known biology behind tissue specificity and provide new valuable insights in a less studied but valuable model species. PMID:23049964

Respiratory syncytial virus nonstructural proteins decrease levels of multiple members of the cellular interferon pathways.

PubMed

Swedan, Samer; Musiyenko, Alla; Barik, Sailen

2009-10-01

Viruses of the Paramyxoviridae family, such as the respiratory syncytial virus (RSV), suppress cellular innate immunity represented by type I interferon (IFN) for optimal growth in their hosts. The two unique nonstructural (NS) proteins, NS1 and NS2, of RSV suppress IFN synthesis, as well as IFN function, but their exact targets are still uncharacterized. Here, we investigate if either or both of the NS proteins affect the steady-state levels of key members of the IFN pathway. We found that both NS1 and NS2 decreased the levels of TRAF3, a strategic integrator of multiple IFN-inducing signals, although NS1 was more efficient. Only NS1 reduced IKKepsilon, a key protein kinase that specifically phosphorylates and activates IFN regulatory factor 3. Loss of the TRAF3 and IKKepsilon proteins appeared to involve a nonproteasomal mechanism. Interestingly, NS2 modestly increased IKKepsilon levels. In the IFN response pathway, NS2 decreased the levels of STAT2, the essential transcription factor for IFN-inducible antiviral genes. Preliminary mapping revealed that the C-terminal 10 residues of NS1 were essential for reducing IKKepsilon levels and the C-terminal 10 residues of NS2 were essential for increasing and reducing IKKepsilon and STAT2, respectively. In contrast, deletion of up to 20 residues of the C termini of NS1 and NS2 did not diminish their TRAF3-reducing activity. Coimmunoprecipitation studies revealed that NS1 and NS2 form a heterodimer. Clearly, the NS proteins of RSV, working individually and together, regulate key signaling molecules of both the IFN activation and response pathways.

Identification of key regulators for the migration and invasion of rheumatoid synoviocytes through a systems approach

PubMed Central

You, Sungyong; Yoo, Seung-Ah; Choi, Susanna; Kim, Ji-Young; Park, Su-Jung; Ji, Jong Dae; Kim, Tae-Hwan; Kim, Ki-Jo; Cho, Chul-Soo; Hwang, Daehee; Kim, Wan-Uk

2014-01-01

Rheumatoid synoviocytes, which consist of fibroblast-like synoviocytes (FLSs) and synovial macrophages (SMs), are crucial for the progression of rheumatoid arthritis (RA). Particularly, FLSs of RA patients (RA-FLSs) exhibit invasive characteristics reminiscent of cancer cells, destroying cartilage and bone. RA-FLSs and SMs originate differently from mesenchymal and myeloid cells, respectively, but share many pathologic functions. However, the molecular signatures and biological networks representing the distinct and shared features of the two cell types are unknown. We performed global transcriptome profiling of FLSs and SMs obtained from RA and osteoarthritis patients. By comparing the transcriptomes, we identified distinct molecular signatures and cellular processes defining invasiveness of RA-FLSs and proinflammatory properties of RA-SMs, respectively. Interestingly, under the interleukin-1β (IL-1β)–stimulated condition, the RA-FLSs newly acquired proinflammatory signature dominant in RA-SMs without losing invasive properties. We next reconstructed a network model that delineates the shared, RA-FLS–dominant (invasive), and RA-SM–dominant (inflammatory) processes. From the network model, we selected 13 genes, including periostin, osteoblast-specific factor (POSTN) and twist basic helix–loop–helix transcription factor 1 (TWIST1), as key regulator candidates responsible for FLS invasiveness. Of note, POSTN and TWIST1 expressions were elevated in independent RA-FLSs and further instigated by IL-1β. Functional assays demonstrated the requirement of POSTN and TWIST1 for migration and invasion of RA-FLSs stimulated with IL-1β. Together, our systems approach to rheumatoid synovitis provides a basis for identifying key regulators responsible for pathological features of RA-FLSs and -SMs, demonstrating how a certain type of cells acquires functional redundancy under chronic inflammatory conditions. PMID:24374632

New insights into the pathways initiating and driving pancreatitis

PubMed Central

Gukovskaya, Anna S.; Pandol, Stephen J.; Gukovsky, Ilya

2016-01-01

Purpose of review In this article, we discuss recent studies that advance our understanding of molecular and cellular factors initiating and driving pancreatitis, with the emphasis on the role of acinar cell organelle disorders. Recent findings The central physiologic function of the pancreatic acinar cell – to synthesize, store, and secrete digestive enzymes – critically relies on coordinated actions of the endoplasmic reticulum (ER), the endolysosomal system, mitochondria, and autophagy. Recent studies begin to unravel the roles of these organelles’ disordering in the mechanism of pancreatitis. Mice deficient in key autophagy mediators Atg5 or Atg7, or lysosome-associated membrane protein-2, exhibit dysregulation of multiple signaling and metabolic pathways in pancreatic acinar cells and develop spontaneous pancreatitis. Mitochondrial dysfunction caused by sustained opening of the permeability transition pore is shown to mediate pancreatitis in several clinically relevant experimental models, and its inhibition by pharmacologic or genetic means greatly reduces local and systemic pathologic responses. Experimental pancreatitis is also alleviated with inhibitors of ORAI1, a key component of the plasma membrane channel mediating pathologic rise in acinar cell cytosolic Ca2+. Pancreatitis-promoting mutations are increasingly associated with the ER stress. These findings suggest novel pathways and drug targets for pancreatitis treatment. In addition, the recent studies identify new mediators (e.g., neutrophil extracellular traps) of the inflammatory and other responses of pancreatitis. Summary The recent findings illuminate a critical role of organelles regulating the autophagic, endolysosomal, mitochondrial, and ER pathways in maintaining pancreatic acinar cell homeostasis and secretory function; provide compelling evidence that organelle disordering is a key pathogenic mechanism initiating and driving pancreatitis; and identify molecular and cellular factors that could be targeted to restore organellar functions and thus alleviate or treat pancreatitis. PMID:27428704

A Role for the GCC-Box in Jasmonate-Mediated Activation of the PDF1.2 Gene of Arabidopsis1

PubMed Central

Brown, Rebecca L.; Kazan, Kemal; McGrath, Ken C.; Maclean, Don J.; Manners, John M.

2003-01-01

The PDF1.2 gene of Arabidopsis encoding a plant defensin is commonly used as a marker for characterization of the jasmonate-dependent defense responses. Here, using PDF1.2 promoter-deletion lines linked to the β-glucoronidase-reporter gene, we examined putative promoter elements associated with jasmonate-responsive expression of this gene. Using stably transformed plants, we first characterized the extended promoter region that positively regulates basal expression from the PDF1.2 promoter. Second, using promoter deletion constructs including one from which the GCC-box region was deleted, we observed a substantially lower response to jasmonate than lines carrying this motif. In addition, point mutations introduced into the core GCC-box sequence substantially reduced jasmonate responsiveness, whereas addition of a 20-nucleotide-long promoter element carrying the core GCC-box and flanking nucleotides provided jasmonate responsiveness to a 35S minimal promoter. Taken together, these results indicated that the GCC-box plays a key role in conferring jasmonate responsiveness to the PDF1.2 promoter. However, deletion or specific mutations introduced into the core GCC-box did not completely abolish the jasmonate responsiveness of the promoter, suggesting that the other promoter elements lying downstream from the GCC-box region may also contribute to jasmonate responsiveness. In other experiments, we identified a jasmonate- and pathogen-responsive ethylene response factor transcription factor, AtERF2, which when overexpressed in transgenic Arabidopsis plants activated transcription from the PDF1.2, Thi2.1, and PR4 (basic chitinase) genes, all of which contain a GCC-box sequence in their promoters. Our results suggest that in addition to their roles in regulating ethylene-mediated gene expression, ethylene response factors also appear to play important roles in regulating jasmonate-responsive gene expression, possibly via interaction with the GCC-box. PMID:12805630

The bHLH transcription factor GmPIB1 facilitates resistance to Phytophthora sojae in Glycine max

PubMed Central

Cheng, Qun; Dong, Lidong; Gao, Tianjiao; Liu, Tengfei; Li, Ninghui; Wang, Le; Chang, Xin; Wu, Junjiang; Xu, Pengfei

2018-01-01

Abstract Phytophthora sojae Kaufmann and Gerdemann causes Phytophthora root rot, a destructive soybean disease worldwide. A basic helix–loop–helix (bHLH) transcription factor is thought to be involved in the response to P. sojae infection in soybean, as revealed by RNA sequencing (RNA-seq). However, the molecular mechanism underlying this response is currently unclear. Here, we explored the function and underlying mechanisms of a bHLH transcription factor in soybean, designated GmPIB1 (P. sojae-inducible bHLH transcription factor), during host responses to P. sojae. GmPIB1 was significantly induced by P. sojae in the resistant soybean cultivar ‘L77-1863’. Analysis of transgenic soybean hairy roots with elevated or reduced expression of GmPIB1 demonstrated that GmPIB1 enhances resistance to P. sojae and reduces reactive oxygen species (ROS) accumulation. Quantitative reverse transcription PCR and chromatin immunoprecipitation–quantitative PCR assays revealed that GmPIB1 binds directly to the promoter of GmSPOD1 and represses its expression; this gene encodes a key enzyme in ROS production. Moreover, transgenic soybean hairy roots with GmSPOD1 silencing through RNA interference exhibited improved resistance to P. sojae and reduced ROS generation. These findings suggest that GmPIB1 enhances resistance to P. sojae by repressing the expression of GmSPOD1. PMID:29579245

Heritability of brain activity related to response inhibition: A longitudinal genetic study in adolescent twins.

PubMed

Anokhin, Andrey P; Golosheykin, Simon; Grant, Julia D; Heath, Andrew C

2017-05-01

The ability to inhibit prepotent but context- or goal-inappropriate responses is essential for adaptive self-regulation of behavior. Deficits in response inhibition, a key component of impulsivity, have been implicated as a core dysfunction in a range of neuropsychiatric disorders such as ADHD and addictions. Identification of genetically transmitted variation in the neural underpinnings of response inhibition can help to elucidate etiological pathways to these disorders and establish the links between genes, brain, and behavior. However, little is known about genetic influences on the neural mechanisms of response inhibition during adolescence, a developmental period characterized by weak self-regulation of behavior. Here we investigated heritability of ERPs elicited in a Go/No-Go task in a large sample of adolescent twins assessed longitudinally at ages 12, 14, and 16. Genetic analyses showed significant heritability of inhibition-related frontal N2 and P3 components at all three ages, with 50 to 60% of inter-individual variability being attributable to genetic factors. These genetic influences included both common genetic factors active at different ages and novel genetic influences emerging during development. Finally, individual differences in the rate of developmental changes from age 12 to age 16 were significantly influenced by genetic factors. In conclusion, the present study provides the first evidence for genetic influences on neural correlates of response inhibition during adolescence and suggests that ERPs elicited in the Go/No-Go task can serve as intermediate neurophysiological phenotypes (endophenotypes) for the study of disinhibition and impulse control disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Heritability of brain activity related to response inhibition: a longitudinal genetic study in adolescent twins

PubMed Central

Anokhin, Andrey P.; Golosheykin, Simon; Grant, Julia D.; Heath, Andrew C.

2017-01-01

The ability to inhibit prepotent but context- or goal-inappropriate responses is essential for adaptive self-regulation of behavior. Deficits in response inhibition, a key component of impulsivity, have been implicated as a core dysfunction in a range of neuropsychiatric disorders such as ADHD and addictions. Identification of genetically transmitted variation in the neural underpinnings of response inhibition can help to elucidate etiological pathways to these disorders and establish the links between genes, brain, and behavior. However, little is known about genetic influences on the neural mechanisms of response inhibition during adolescence, a developmental period characterized by weak self-regulation of behavior. Here we investigated heritability of ERPs elicited in a Go/No-Go task in a large sample of adolescent twins assessed longitudinally at ages 12, 14, and 16. Genetic analyses showed significant heritability of inhibition-related frontal N2 and P3 components at all three ages, with 50 to 60% of inter-individual variability being attributable to genetic factors. These genetic influences included both common genetic factors active at different ages and novel genetic influences emerging during development. Finally, individual differences in the rate of developmental changes from age 12 to age 16 were significantly influenced by genetic factors. In conclusion, the present study provides the first evidence for genetic influences on neural correlates of response inhibition during adolescence and suggests that ERPs elicited in the Go/No-Go task can serve as intermediate neurophysiological phenotypes (endophenotypes) for the study of disinhibition and impulse control disorders. PMID:28300615

Mechanisms of the placebo response in pain in osteoarthritis.

PubMed

Abhishek, A; Doherty, M

2013-09-01

Administration of a placebo associates with symptomatic improvement in many conditions--the so-called placebo response. In this review we explain the concept of placebo response, examine the data that supports existence in osteoarthritis (OA), and discuss its possible mechanisms and determinants. A Pubmed literature search was carried out. Key articles were identified, and their findings discussed in a narrative review. Pain, stiffness, self-reported function and physician-global assessment in OA clearly improve in response to placebo. However, more objective measures such as quadriceps strength and radiographic progression appear less responsive. Although not directly studied in OA, contextual effects, patient expectation and conditioning are believed to be the main mechanisms. Neurotransmitter changes that mediate placebo-induced analgesia include increased endogenous opioid levels, increased dopamine levels, and reduced levels of cholecystokinin. Almost all parts of the brain involved in pain processing are influenced during placebo-induced analgesia. Determinants of the magnitude of placebo response include the patient-practitioner interaction, treatment response expectancy, knowledge of being treated, patient personality traits and placebo specific factors such as the route and frequency of administration, branding, and treatment costs. Clearer understanding of the neurobiology of placebo response validates its existence as a real phenomenon. Although routine administration of placebo for symptomatic improvement is difficult to justify, contextual factors that enhance treatment response should be employed in the management of chronic painful conditions such as OA where available treatments have only modest efficacy. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Tackling childhood obesity: the importance of understanding the context.

PubMed

Knai, Cécile; McKee, Martin

2010-12-01

Recommendations to tackle major health problems such as childhood obesity may not be appropriate if they fail to take account of the prevailing socio-political, cultural and economic context. We describe the development and application of a qualitative risk analysis approach to identify non-scientific considerations framing the policy response to obesity in Denmark and Latvia. Interviews conducted with key stakeholders in Denmark and Latvia, undertaken following a review of relevant literature on obesity and national policies. A qualitative risk analysis model was developed to help explain the findings in the light of national context. Non-scientific considerations that appeared to influence the response to obesity include the perceived relative importance of childhood obesity; the nature of stakeholder relations and its impact on decision-making; the place of obesity on the policy agenda; the legitimacy of the state to act for population health and views on alliances between public and private sectors. Better recognition of the exogenous factors affecting policy-making may lead to a more adequate policy response. The development and use of a qualitative risk analysis model enabled a better understanding of the contextual factors and processes influencing the response to childhood obesity in each country.

Modeling Systems-Level Regulation of Host Immune Responses

PubMed Central

Thakar, Juilee; Pilione, Mylisa; Kirimanjeswara, Girish; Harvill, Eric T; Albert, Réka

2007-01-01

Many pathogens are able to manipulate the signaling pathways responsible for the generation of host immune responses. Here we examine and model a respiratory infection system in which disruption of host immune functions or of bacterial factors changes the dynamics of the infection. We synthesize the network of interactions between host immune components and two closely related bacteria in the genus Bordetellae. We incorporate existing experimental information on the timing of immune regulatory events into a discrete dynamic model, and verify the model by comparing the effects of simulated disruptions to the experimental outcome of knockout mutations. Our model indicates that the infection time course of both Bordetellae can be separated into three distinct phases based on the most active immune processes. We compare and discuss the effect of the species-specific virulence factors on disrupting the immune response during their infection of naive, antibody-treated, diseased, or convalescent hosts. Our model offers predictions regarding cytokine regulation, key immune components, and clearance of secondary infections; we experimentally validate two of these predictions. This type of modeling provides new insights into the virulence, pathogenesis, and host adaptation of disease-causing microorganisms and allows systems-level analysis that is not always possible using traditional methods. PMID:17559300

TG2 regulates the heat-shock response by the post-translational modification of HSF1.

PubMed

Rossin, Federica; Villella, Valeria Rachela; D'Eletto, Manuela; Farrace, Maria Grazia; Esposito, Speranza; Ferrari, Eleonora; Monzani, Romina; Occhigrossi, Luca; Pagliarini, Vittoria; Sette, Claudio; Cozza, Giorgio; Barlev, Nikolai A; Falasca, Laura; Fimia, Gian Maria; Kroemer, Guido; Raia, Valeria; Maiuri, Luigi; Piacentini, Mauro

2018-05-11

Heat-shock factor 1 (HSF1) is the master transcription factor that regulates the response to proteotoxic stress by controlling the transcription of many stress-responsive genes including the heat-shock proteins. Here, we show a novel molecular mechanism controlling the activation of HSF1. We demonstrate that transglutaminase type 2 (TG2), dependent on its protein disulphide isomerase activity, triggers the trimerization and activation of HSF1 regulating adaptation to stress and proteostasis impairment. In particular, we find that TG2 loss of function correlates with a defect in the nuclear translocation of HSF1 and in its DNA-binding ability to the HSP70 promoter. We show that the inhibition of TG2 restores the unbalance in HSF1-HSP70 pathway in cystic fibrosis (CF), a human disorder characterized by deregulation of proteostasis. The absence of TG2 leads to an increase of about 40% in CFTR function in a new experimental CF mouse model lacking TG2. Altogether, these results indicate that TG2 plays a key role in the regulation of cellular proteostasis under stressful cellular conditions through the modulation of the heat-shock response. © 2018 The Authors.

Do diabetes and obesity affect the metabolic response to exercise?

PubMed

Plomgaard, Peter; Weigert, Cora

2017-07-01

Exercise is recommended as therapeutic intervention for people at risk to develop type 2 diabetes to prevent or treat the disease. Recent studies on the influence of obesity and type 2 diabetes on the outcome of exercise programs are discussed. Poor glycemic control before an intervention can be a risk factor of reduced therapeutic benefit from exercise. But the acute metabolic response to exercise and the transcriptional profile of the working muscle is similar in healthy controls and type 2 diabetic patients, including but not limited to intact activation of skeletal muscle AMP-activated kinase signaling, glucose uptake and expression of peroxisome proliferator-activated receptor gamma coactivator 1α. The increase in plasma acylcarnitines during exercise is not influenced by type 2 diabetes or obesity. The hepatic response to exercise is dependent on the glucagon/insulin ratio and the exercise-induced increase in hepatokines such as fibroblast growth factor 21 and follistatin is impaired in type 2 diabetes and obesity, but consequences for the benefit from exercise are unknown yet. Severe metabolic dysregulation can reduce the benefit from exercise, but the intact response of key metabolic regulators in exercising skeletal muscle of diabetic patients demonstrates the effectiveness of exercise programs to treat the disease.

Resveratrol upregulates Egr-1 expression and activity involving extracellular signal-regulated protein kinase and ternary complex factors

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

Rössler, Oliver G.; Glatzel, Daniel; Thiel, Gerald, E-mail: gerald.thiel@uks.eu

2015-03-01

Many intracellular functions have been attributed to resveratrol, a polyphenolic phytoalexin found in grapes and in other plants. Here, we show that resveratrol induces the expression of the transcription factor Egr-1 in human embryonic kidney cells. Using a chromosomally embedded Egr-1-responsive reporter gene, we show that the Egr-1 activity was significantly elevated in resveratrol-treated cells, indicating that the newly synthesized Egr-1 protein was biologically active. Stimulus-transcription coupling leading to the resveratrol-induced upregulation of Egr-1 expression and activity requires the protein kinases Raf and extracellular signal-regulated protein kinase ERK, while MAP kinase phosphatase-1 functions as a nuclear shut-off device that interruptsmore » the signaling cascade connecting resveratrol stimulation with enhanced Egr-1 expression. On the transcriptional level, Elk-1, a key transcriptional regulator of serum response element-driven gene transcription, connects the intracellular signaling cascade elicited by resveratrol with transcription of the Egr-1 gene. These data were corroborated by the observation that stimulation of the cells with resveratrol increased the transcriptional activation potential of Elk-1. The SRE as well as the GC-rich DNA binding site of Egr-1 function as resveratrol-responsive elements. Thus, resveratrol regulates gene transcription via activation of the stimulus-regulated protein kinases Raf and ERK and the stimulus-responsive transcription factors TCF and Egr-1. - Highlights: • The plant polyphenol resveratrol upregulates Egr-1 expression and activity. • The stimulation of Egr-1 requires the protein kinases ERK and Raf. • Resveratrol treatment upregulates the transcriptional activation potential of Elk-1. • Resveratrol-induced stimulation of Egr-1 requires ternary complex factors. • Two distinct resveratrol-responsive elements were identified.« less

Development of new geomagnetic storm ground response scaling factors for utilization in hazard assessments

NASA Astrophysics Data System (ADS)

Pulkkinen, A. A.; Bernabeu, E.; Weigel, R. S.; Kelbert, A.; Rigler, E. J.; Bedrosian, P.; Love, J. J.

2017-12-01

Development of realistic storm scenarios that can be played through the exposed systems is one of the key requirements for carrying out quantitative space weather hazards assessments. In the geomagnetically induced currents (GIC) and power grids context, these scenarios have to quantify the spatiotemporal evolution of the geoelectric field that drives the potentially hazardous currents in the system. In response to the Federal Energy Regulatory Commission (FERC) order 779, a team of scientists and engineers that worked under the auspices of North American Electric Reliability Corporation (NERC), has developed extreme geomagnetic storm and geoelectric field benchmark(s) that use various scaling factors that account for geomagnetic latitude and ground structure of the locations of interest. These benchmarks, together with the information generated in the National Space Weather Action Plan, are the foundation for the hazards assessments that the industry will be carrying out in response to the FERC order and under the auspices of the National Science and Technology Council. While the scaling factors developed in the past work were based on the best available information, there is now significant new information available for parts of the U.S. pertaining to the ground response to external geomagnetic field excitation. The significant new information includes the results magnetotelluric surveys that have been conducted over the past few years across the contiguous US and results from previous surveys that have been made available in a combined online database. In this paper, we distill this new information in the framework of the NERC benchmark and in terms of updated ground response scaling factors thereby allowing straightforward utilization in the hazard assessments. We also outline the path forward for improving the overall extreme event benchmark scenario(s) including generalization of the storm waveforms and geoelectric field spatial patterns.

Immunological pathogenesis of inflammatory bowel disease.

PubMed

Lee, Seung Hoon; Kwon, Jeong Eun; Cho, Mi-La

2018-01-01

Inflammatory bowel disease (IBD) is a chronic inflammatory state of the gastrointestinal tract and can be classified into 2 main clinical phenomena: Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis of IBD, including CD and UC, involves the presence of pathogenic factors such as abnormal gut microbiota, immune response dysregulation, environmental changes, and gene variants. Although many investigations have tried to identify novel pathogenic factors associated with IBD that are related to environmental, genetic, microbial, and immune response factors, a full understanding of IBD pathogenesis is unclear. Thus, IBD treatment is far from optimal, and patient outcomes can be unsatisfactory. As result of massive studying on IBD, T helper 17 (Th17) cells and innate lymphoid cells (ILCs) are investigated on their effects on IBD. A recent study of the plasticity of Th17 cells focused primarily on colitis. ILCs also emerging as novel cell family, which play a role in the pathogenesis of IBD. IBD immunopathogenesis is key to understanding the causes of IBD and can lead to the development of IBD therapies. The aim of this review is to explain the pathogenesis of IBD, with a focus on immunological factors and therapies.

Taking the hit: focusing on caregiver "error" masks organizational-level risk factors for nursing aide assault.

PubMed

Morgan, Debra G; Crossley, Margaret F; Stewart, Norma J; D'Arcy, Carl; Forbes, Dorothy A; Normand, Sandy A; Cammer, Allison L

2008-03-01

Beliefs about the causes of events have implications for emotional reactions, distress, expectations for the future, and behavioral responses. In this article we report on two issues: the organizational context that contributes to nursing aide (NA) assault and reporting, and serendipitous findings that arose from investigating unexpected response rates to a survey. Data were collected in 11 rural nursing homes using a structured prospective event-reporting diary to collect detailed information about incidents of physical aggression, followed by focus groups to further explore NAs' perceptions of these events. Here we report on analysis of 19 focus groups conducted with 138 NAs. Participants described organizational-level factors that constrained their practice, affected their interactions with residents, and created a context that put them at risk for physical assault. These factors also affected their willingness to provide written documentation about aggressive incidents. The key issues were frustration at being blamed for causing aggression, lack of action to address the problem, and a desire for respect and involvement in decision making. Organizational changes are needed to modify the contextual factors contributing to assault risk. Researchers must be willing to modify study designs to more fully understand the nature of the problem studied.

Biomass Allocation Patterns across China’s Terrestrial Biomes

PubMed Central

Wang, Limei; Li, Longhui; Chen, Xi; Tian, Xin; Wang, Xiaoke; Luo, Geping

2014-01-01

Root to shoot ratio (RS) is commonly used to describe the biomass allocation between below- and aboveground parts of plants. Determining the key factors influencing RS and interpreting the relationship between RS and environmental factors is important for biological and ecological research. In this study, we compiled 2088 pairs of root and shoot biomass data across China’s terrestrial biomes to examine variations in the RS and its responses to biotic and abiotic factors including vegetation type, soil texture, climatic variables, and stand age. The median value of RS (RSm) for grasslands, shrublands, and forests was 6.0, 0.73, and 0.23, respectively. The range of RS was considerably wide for each vegetation type. RS values for all three major vegetation types were found to be significantly correlated to mean annual precipitation (MAP) and potential water deficit index (PWDI). Mean annual temperature (MAT) also significantly affect the RS for forests and grasslands. Soil texture and forest origin altered the response of RS to climatic factors as well. An allometric formula could be used to well quantify the relationship between aboveground and belowground biomass, although each vegetation type had its own inherent allometric relationship. PMID:24710503

Delayed recovery from anesthesia: A postgraduate educational review.

PubMed

Misal, Ullhas Sudhakarrao; Joshi, Suchita Annasaheb; Shaikh, Mudassir Mohd

2016-01-01

Delayed awakening from anesthesia remains one of the biggest challenges that involve an anesthesiologist. With the general use of fast-acting anesthetic agents, patients usually awaken quickly in the postoperative period. The time to emerge from anesthesia is affected by patient factors, anesthetic factors, duration of surgery, and painful stimulation. The principal factors responsible for delayed awakening following anesthesia are anesthetic agents and medications used in the perioperative period. Nonpharmacological causes may have a serious sequel, hence recognizing these organic conditions is important. Certain underlying metabolic disorders such as hypoglycemia, severe hyperglycemia, and electrolyte imbalance, especially hypernatremia, hypoxia, hypercapnia, central anticholinergic syndrome, chronic hypertension, liver disease, hypoalbuminemia, uremia, and severe hypothyroidism may also be responsible for delayed recovery following anesthesia. Unexpected delayed emergence after general anesthesia may also be due to intraoperative cerebral hypoxia, hemorrhage, embolism, or thrombosis. Accurate diagnosis of the underlying cause is the key for the institution of appropriate therapy, but primary management is to maintain airway, breathing, and circulation. This comprehensive review discusses the risk factors, causes, evaluation and management of delayed recovery based on our clinical experience, and literature search on the internet, supported by the standard textbooks of anesthesiology.

The aquaglyceroporin AQP9 contributes to the sex-specific effects of in utero arsenic exposure on placental gene expression.

PubMed

Winterbottom, Emily F; Koestler, Devin C; Fei, Dennis Liang; Wika, Eric; Capobianco, Anthony J; Marsit, Carmen J; Karagas, Margaret R; Robbins, David J

2017-06-14

Sex-specific factors play a major role in human health and disease, including responses to environmental stresses such as toxicant exposure. Increasing evidence suggests that such sex differences also exist during fetal development. In a previous report using the resources of the New Hampshire Birth Cohort Study (NHBCS), we found that low-to-moderate in utero exposure to arsenic, a highly toxic and widespread pollutant, was associated with altered expression of several key developmental genes in the fetal portion of the placenta. These associations were sex-dependent, suggesting that in utero arsenic exposure differentially impacts male and female fetuses. In the present study, we investigated the molecular basis for these sex-specific responses to arsenic. Using NanoString technology, we further analyzed the fetal placenta samples from the NHBCS for the expression of genes encoding arsenic transporters and metabolic enzymes. Multivariable linear regression analysis was used to examine their relationship with arsenic exposure and with key developmental genes, after stratification by fetal sex. We found that maternal arsenic exposure was strongly associated with expression of the AQP9 gene, encoding an aquaglyceroporin transporter, in female but not male fetal placenta. Moreover, AQP9 expression associated with that of a subset of female-specific arsenic-responsive genes. Our results suggest that AQP9 is upregulated in response to arsenic exposure in female, but not male, fetal placenta. Based on these results and prior studies, increased AQP9 expression may lead to increased arsenic transport in the female fetal placenta, which in turn may alter the expression patterns of key developmental genes that we have previously shown to be associated with arsenic exposure. Thus, this study suggests that AQP9 may play a role in the sex-specific effects of in utero arsenic exposure.

Assessment of factors influencing preservation of dignity at life's end: creation and the cross-cultural validation of the preservation of dignity card-sort tool.

PubMed

Periyakoil, Vyjeyanthi S; Noda, Arthur M; Kraemer, Helena Chmura

2010-05-01

Preserving patient dignity is a sentinel premise of palliative care. This study was conducted to gain a better understanding of factors influencing preservation of dignity in the last chapter of life. We conducted an open-ended written survey of 100 multidisciplinary providers (69% response rate) and responses were categorized to identify 2 main themes, 5 subthemes, and 10 individual factors that were used to create the preservation of dignity card-sort tool (p-DCT). The 10-item rank order tool was administered to a cohort of community dwelling Filipino Americans (n = 140, age mean = 61.3, 45% male and 55% female). A Spearman correlation matrix was constructed for all the 10 individual factors as well as the themes and subthemes based on the data generated by the subjects. The individual factors were minimally correlated with each other indicating that each factor was an independent stand-alone factor. The median, 25th and 75th percentile ranks were calculated and "s/he has self-respect" (intrinsic theme, self-esteem subtheme) emerged as the most important factor (mean rank 3.0 and median rank 2.0) followed by "others treat her/him with respect" (extrinsic theme, respect subtheme) with a mean rank = 3.6 and median = 3.0. The p-DCT is a simple, rank order card-sort tool that may help clinicians identify patients' perceptions of key factors influencing the preservation of their dignity in the last chapter of life.

Defining teaching hospitals' GME strategy in response to new financial and market challenges.

PubMed

Wray, J L; Sadowski, S M

1998-04-01

The authors present an overview of current graduate medical education (GME) issues, particularly the financial challenges to teaching hospitals resulting from the Balanced Budget and Tax Payer Relief Acts of 1997 and other recent market-driven factors. They describe in detail the nature of Medicare GME payments before and after the 1997 legislation, with specific examples, and explain the negative financial impact of the legislation and aspects of the legislation that are designed to alleviate that impact. Other factors influencing GME program size and composition are also discussed, including oversupplies or shortages of physicians, the concern that teaching hospitals are using public funds to train international medical graduates, changing training requirements, etc. The authors also describe a recent consulting assignment during which they assisted a major teaching hospital to develop a GME strategy that was responsive to the organization's mission and patients and that took into account future GME financing challenges. Detailed explanations are given of how the consultants analyzed the hospital's GME programs and finances, developed and ranked key institution-specific program criteria (strategic, organizational and operational, and financial), and, in consultation with all key stakeholders, formulated a GME strategy specific to the institution's needs. The authors conclude by cautioning that each institution's GME strategy will be different, but that it is important for institutions to develop such strategies to better face future challenges.

The Future of Clinical Education: Using Futuristic Scenarios to Explore Allied Health Deans' Perspectives on Clinical Education.

PubMed

Romig, Barbara D; Tucker, Ann W; Hewitt, Anne M; O'Sullivan Maillet, Julie

2017-01-01

There is limited information and consensus on the future of clinical education. The Delphi technique was selected to identify agreement among Association of Schools of Allied Health Professions' (ASAHP) allied health deans on the future (2018-2023) of allied health (AH) clinical education. Sixty-one AH deans, 54.9% (61 of 111) of the ASAHP membership, expressed opinions about clinical education through a three-round Delphi study. In conjunction with a conceptual model, four futuristic scenarios were used to encourage deans' feedback on the key factors impacting the future of clinical education. The responses to the four scenarios showed ways the external environment influences which activities the deans recommend. The results presented, by individual scenario and in totality, provide relevant and timely information on the importance and transformation of AH clinical education and its future. Futuristic scenarios, in combination with the Delphi technique, generated information where little exists specific to AH deans' perspectives on AH clinical education. The results offer deans opportunities for future strategic improvements. The use of the futuristic scenarios was suitable for guiding deans' responses and reaching agreement on the future of AH clinical education. These contributions reflect the imminent conditions and healthcare environment identified in the various scenarios and provide additional insight on key factors impacting the future for AH clinical education.

Concept Mapping of PMTCT Implementation Challenges and Solutions Across 6 sub-Saharan African Countries in the NIH-PEPFAR PMTCT Implementation Science Alliance.

PubMed

Aarons, Gregory A; Sommerfeld, David H; Chi, Benjamin H; Ezeanolue, Echezona E; Sturke, Rachel; Guay, Laura; Siberry, George K

2016-08-01

Although tremendous gains have been made to reduce mother-to-child HIV transmission (MTCT) globally, evidence-based practice implementation remains inconsistent in sub-Saharan Africa. We sought to identify the key domains for effective prevention of MTCT (PMTCT) implementation, using a participatory mixed-methods approach. Participants were members of the NIH-PEPFAR PMTCT Implementation Science Alliance (ISA), a platform of researchers, public-health practitioners, policymakers, and donors supported through NIH/PEPFAR. We used concept mapping to identify priority areas for PMTCT implementation science. Participants responded to the focus question: "In your experience, what factors have facilitated or hindered implementation of PMTCT interventions?" Responses were consolidated into discrete statements, grouped together based on similarity, and rated for importance, changeability, and extent to which ISA participation enhanced the capacity to influence/change the factor. Using multidimensional scaling and cluster analysis, we identified 12 key domains of PMTCT implementation. Two domains (Governmental Commitment and Data Measurement & Collection) were consistently ranked at or near the top for overall importance, perceived changeability, and enhanced ability to address through ISA participation. Through a stakeholder-based, participatory approach, we identified key domains for that should be considered for future PMTCT implementation research in sub-Saharan Africa.

Determinants of sustainability in solid waste management--the Gianyar Waste Recovery Project in Indonesia.

PubMed

Zurbrügg, Christian; Gfrerer, Margareth; Ashadi, Henki; Brenner, Werner; Küper, David

2012-11-01

According to most experts, integrated and sustainable solid waste management should not only be given top priority, but must go beyond technical aspects to include various key elements of sustainability to ensure success of any solid waste project. Aside from project sustainable impacts, the overall enabling environment is the key feature determining performance and success of an integrated and affordable solid waste system. This paper describes a project-specific approach to assess typical success or failure factors. A questionnaire-based assessment method covers issues of: (i) social mobilisation and acceptance (social element), (ii) stakeholder, legal and institutional arrangements comprising roles, responsibilities and management functions (institutional element); (iii) financial and operational requirements, as well as cost recovery mechanisms (economic element). The Gianyar Waste Recovery Project in Bali, Indonesia was analysed using this integrated assessment method. The results clearly identified chief characteristics, key factors to consider when planning country wide replication but also major barriers and obstacles which must be overcome to ensure project sustainability. The Gianyar project consists of a composting unit processing 60 tons of municipal waste per day from 500,000 inhabitants, including manual waste segregation and subsequent composting of the biodegradable organic fraction. Copyright © 2012 Elsevier Ltd. All rights reserved.

Arabidopsis WRKY33 Is a Key Transcriptional Regulator of Hormonal and Metabolic Responses toward Botrytis cinerea Infection1[W

PubMed Central

Birkenbihl, Rainer P.; Diezel, Celia; Somssich, Imre E.

2012-01-01

The Arabidopsis (Arabidopsis thaliana) transcription factor WRKY33 is essential for defense toward the necrotrophic fungus Botrytis cinerea. Here, we aimed at identifying early transcriptional responses mediated by WRKY33. Global expression profiling on susceptible wrky33 and resistant wild-type plants uncovered massive differential transcriptional reprogramming upon B. cinerea infection. Subsequent detailed kinetic analyses revealed that loss of WRKY33 function results in inappropriate activation of the salicylic acid (SA)-related host response and elevated SA levels post infection and in the down-regulation of jasmonic acid (JA)-associated responses at later stages. This down-regulation appears to involve direct activation of several jasmonate ZIM-domain genes, encoding repressors of the JA-response pathway, by loss of WRKY33 function and by additional SA-dependent WRKY factors. Moreover, genes involved in redox homeostasis, SA signaling, ethylene-JA-mediated cross-communication, and camalexin biosynthesis were identified as direct targets of WRKY33. Genetic studies indicate that although SA-mediated repression of the JA pathway may contribute to the susceptibility of wrky33 plants to B. cinerea, it is insufficient for WRKY33-mediated resistance. Thus, WRKY33 apparently directly targets other still unidentified components that are also critical for establishing full resistance toward this necrotroph. PMID:22392279

Keys and seats: Spatial response coding underlying the joint spatial compatibility effect.

PubMed

Dittrich, Kerstin; Dolk, Thomas; Rothe-Wulf, Annelie; Klauer, Karl Christoph; Prinz, Wolfgang

2013-11-01

Spatial compatibility effects (SCEs) are typically observed when participants have to execute spatially defined responses to nonspatial stimulus features (e.g., the color red or green) that randomly appear to the left and the right. Whereas a spatial correspondence of stimulus and response features facilitates response execution, a noncorrespondence impairs task performance. Interestingly, the SCE is drastically reduced when a single participant responds to one stimulus feature (e.g., green) by operating only one response key (individual go/no-go task), whereas a full-blown SCE is observed when the task is distributed between two participants (joint go/no-go task). This joint SCE (a.k.a. the social Simon effect) has previously been explained by action/task co-representation, whereas alternative accounts ascribe joint SCEs to spatial components inherent in joint go/no-go tasks that allow participants to code their responses spatially. Although increasing evidence supports the idea that spatial rather than social aspects are responsible for joint SCEs emerging, it is still unclear to which component(s) the spatial coding refers to: the spatial orientation of response keys, the spatial orientation of responding agents, or both. By varying the spatial orientation of the responding agents (Exp. 1) and of the response keys (Exp. 2), independent of the spatial orientation of the stimuli, in the present study we found joint SCEs only when both the seating and the response key alignment matched the stimulus alignment. These results provide evidence that spatial response coding refers not only to the response key arrangement, but also to the-often neglected-spatial orientation of the responding agents.

Heat shock transcription factor 1-deficiency attenuates overloading-associated hypertrophy of mouse soleus muscle.

PubMed

Koya, Tomoyuki; Nishizawa, Sono; Ohno, Yoshitaka; Goto, Ayumi; Ikuta, Akihiro; Suzuki, Miho; Ohira, Tomotaka; Egawa, Tatsuro; Nakai, Akira; Sugiura, Takao; Ohira, Yoshinobu; Yoshioka, Toshitada; Beppu, Moroe; Goto, Katsumasa

2013-01-01

Hypertrophic stimuli, such as mechanical stress and overloading, induce stress response, which is mediated by heat shock transcription factor 1 (HSF1), and up-regulate heat shock proteins (HSPs) in mammalian skeletal muscles. Therefore, HSF1-associated stress response may play a key role in loading-associated skeletal muscle hypertrophy. The purpose of this study was to investigate the effects of HSF1-deficiency on skeletal muscle hypertrophy caused by overloading. Functional overloading on the left soleus was performed by cutting the distal tendons of gastrocnemius and plantaris muscles for 4 weeks. The right muscle served as the control. Soleus muscles from both hindlimbs were dissected 2 and 4 weeks after the operation. Hypertrophy of soleus muscle in HSF1-null mice was partially inhibited, compared with that in wild-type (C57BL/6J) mice. Absence of HSF1 partially attenuated the increase of muscle wet weight and fiber cross-sectional area of overloaded soleus muscle. Population of Pax7-positive muscle satellite cells in HSF1-null mice was significantly less than that in wild-type mice following 2 weeks of overloading (p<0.05). Significant up-regulations of interleukin (IL)-1β and tumor necrosis factor mRNAs were observed in HSF1-null, but not in wild-type, mice following 2 weeks of overloading. Overloading-related increases of IL-6 and AFT3 mRNA expressions seen after 2 weeks of overloading tended to decrease after 4 weeks in both types of mice. In HSF1-null mice, however, the significant overloading-related increase in the expression of IL-6, not ATF3, mRNA was noted even at 4th week. Inhibition of muscle hypertrophy might be attributed to the greater and prolonged enhancement of IL-6 expression. HSF1 and/or HSF1-mediated stress response may, in part, play a key role in loading-induced skeletal muscle hypertrophy.

Differential Effects of Oral and Intravenous Lipid Administration on Key Molecules Related to Energy Homeostasis

PubMed Central

Vamvini, Maria T.; Hamnvik, Ole-Petter; Sahin-Efe, Ayse; Gavrieli, Anna; Dincer, Fadime; Farr, Olivia M.

2016-01-01

Context: The spectrum of lipid-induced changes in the secretion of hormones important in energy homeostasis has not yet been fully elucidated. Objective: To identify potential incretin-like effects in response to lipid administration, we examined the short-term effect of iv vs oral lipids on key molecules regulating energy homeostasis. Design, Intervention, and Participants: After a 10-hour overnight fast, 26 subjects were randomized to receive an oral lipid load, a 10% iv lipid emulsion, a 20% iv lipid emulsion, or an iv saline infusion. We obtained blood samples at 30-minute intervals for the first 2 hours and hourly thereafter for a total of 6 hours. Main Outcome Measures: Circulating levels of insulin, glucose, c-peptide, free fatty acids, incretins (glucagon-like peptide-1, gastric inhibitory polypeptide), glucagon, peptide YY, ghrelin, fibroblast growth factor 21, fetuin A, irisin, omentin, and adiponectin were measured. Results: Oral lipid ingestion resulted in higher glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon, and peptide YY levels, compared with the other three groups (incremental area under the curve P = .003, P < .001, P < .001, P < .001, respectively). The 20% lipid emulsion, leading to higher free fatty acid levels, resulted in greater insulin, c-peptide, and fibroblast growth factor 21 responses compared with placebo and the other two groups (incremental area under the curve P = .002, P = .005, P < .001, P < .001, respectively). Omentin, adiponectin, fetuin A, and irisin levels were not affected by either mode of lipid administration. Conclusions: Metabolic responses to lipids depend on the route of administration. Only iv lipids trigger a dose-dependent fibroblast growth factor 21 secretion, which is nonglucagon mediated. Intravenous lipids also induce hyperinsulinemia without concurrent decreases in glucose, a phenomenon observed in insulin-resistant states. Orally administered lipids mostly affect gastrointestinal tract-secreted molecules important in glucose and energy homeostasis such as glucagon, incretins, and peptide YY. PMID:26964729

Heat Shock Transcription Factor 1-Deficiency Attenuates Overloading-Associated Hypertrophy of Mouse Soleus Muscle

PubMed Central

Koya, Tomoyuki; Nishizawa, Sono; Ohno, Yoshitaka; Goto, Ayumi; Ikuta, Akihiro; Suzuki, Miho; Ohira, Tomotaka; Egawa, Tatsuro; Nakai, Akira; Sugiura, Takao; Ohira, Yoshinobu; Yoshioka, Toshitada; Beppu, Moroe; Goto, Katsumasa

2013-01-01

Hypertrophic stimuli, such as mechanical stress and overloading, induce stress response, which is mediated by heat shock transcription factor 1 (HSF1), and up-regulate heat shock proteins (HSPs) in mammalian skeletal muscles. Therefore, HSF1-associated stress response may play a key role in loading-associated skeletal muscle hypertrophy. The purpose of this study was to investigate the effects of HSF1-deficiency on skeletal muscle hypertrophy caused by overloading. Functional overloading on the left soleus was performed by cutting the distal tendons of gastrocnemius and plantaris muscles for 4 weeks. The right muscle served as the control. Soleus muscles from both hindlimbs were dissected 2 and 4 weeks after the operation. Hypertrophy of soleus muscle in HSF1-null mice was partially inhibited, compared with that in wild-type (C57BL/6J) mice. Absence of HSF1 partially attenuated the increase of muscle wet weight and fiber cross-sectional area of overloaded soleus muscle. Population of Pax7-positive muscle satellite cells in HSF1-null mice was significantly less than that in wild-type mice following 2 weeks of overloading (p<0.05). Significant up-regulations of interleukin (IL)-1β and tumor necrosis factor mRNAs were observed in HSF1-null, but not in wild-type, mice following 2 weeks of overloading. Overloading-related increases of IL-6 and AFT3 mRNA expressions seen after 2 weeks of overloading tended to decrease after 4 weeks in both types of mice. In HSF1-null mice, however, the significant overloading-related increase in the expression of IL-6, not ATF3, mRNA was noted even at 4th week. Inhibition of muscle hypertrophy might be attributed to the greater and prolonged enhancement of IL-6 expression. HSF1 and/or HSF1-mediated stress response may, in part, play a key role in loading-induced skeletal muscle hypertrophy. PMID:24167582

Injury prevention in child and adolescent sport: whose responsibility is it?

PubMed

Emery, Carolyn A; Hagel, Brent; Morrongiello, Barbara A

2006-11-01

Sport and recreational injuries are a leading cause of morbidity in youth. There is a significant body of literature on risk factors for sport-related injuries and a growing body of research supporting the effectiveness of sport-specific prevention strategies in youth. Given the predictability and preventability of injuries in youth sport, the purpose of this article is to develop a model that considers societal responsibility for injury prevention in youth sport, and to discuss the evidence that supports this model. Previously published papers have provided a basis for expert opinion to discuss an approach to examining the shared societal responsibility for implementing countermeasures to reduce the risk of injury to youth during sports. Based on a historical perspective, broad conceptual framework, and specific evidence for prevention strategies in youth sport, the authors have developed and supported a theoretical model that defines a responsibility hierarchy in preventing injuries in youth sport. An argument has been made for a hierarchy of responsibility, with the lowest level of responsibility assigned to the child, and the highest level to those organizations or groups with the potential to effect the most change. The justification for this approach has been discussed in the context of the desirability of passive prevention strategies, the limited evidence for the effectiveness of strategies relying solely on behavior change in children and parents, and the level of perceptual and cognitive development in children that inadequately prepares them to take primary responsibility for their own safety in sport. The development of effective programs to reduce the burden of sport injury among youth necessitates a scientific approach, the identification of key risk factors for injury, a thorough examination of how factors interact to affect risk, and the identification of potential barriers to the effectiveness of injury-prevention programs.

VIP modulates the pro-inflammatory maternal response, inducing tolerance to trophoblast cells

PubMed Central

Fraccaroli, Laura; Alfieri, Julio; Larocca, Luciana; Calafat, Mario; Roca, Valeria; Lombardi, Eduardo; Ramhorst, Rosanna; Leirós, Claudia Pérez

2009-01-01

Background and purpose Successful embryo implantation is followed by a local pro-inflammatory and Th1 response, subsequently controlled by a Th2 response. Vasoactive intestinal peptide (VIP) has anti-inflammatory effects and promotes tolerogenic/Th2 responses while favouring embryonic development. We investigated the potential regulatory role of VIP on human trophoblast cells, maternal pro-inflammatory responses and trophoblast-maternal leukocyte interactions. Experimental approach We tested VIP effects directly on a trophoblast cell line (Swan 71 cells) and after co-culture with maternal peripheral blood mononuclear cells (PBMCs) as models of the feto-maternal dialogue. We also co-cultured maternal and paternal PBMCs to test effects of endogenous VIP on maternal alloresponses. Key results Swan 71 cells express VPAC1 receptors and VIP induced their proliferation and the expression of leukaemia inhibitor factor, a pro-implantatory marker. After interaction with trophoblast cells, VIP increased Foxp3, the proportion of CD4+CD25+Foxp3+ cells within maternal PBMCs and transforming growth factor β expression. Also, during the trophoblast-maternal PBMCs interaction, VIP reduced pro-inflammatory mediators [interleukin (IL)-6, monocyte chemoattractant protein 1, nitric oxide], while increasing IL-10. Trophoblast cells produced VIP which dose-dependently suppressed allomaternal responses, accompanied by reduced expression of the T cell transcription factor, T-bet. Conclusions and implications Vasoactive intestinal peptide induced pro-implantatory markers and trophoblast cell proliferation, while controlling the initial pro-inflammatory response, by increasing maternal regulatory T cells and anti-inflammatory cytokines. As an autocrine regulatory peptide VIP might contribute to fetal survival through two mechanisms; a direct trophic effect on trophoblast cells and an immunomodulatory effect that favours tolerance to fetal antigens. PMID:19133995

FARO server: Meta-analysis of gene expression by matching gene expression signatures to a compendium of public gene expression data.

PubMed

Manijak, Mieszko P; Nielsen, Henrik B

2011-06-11

Although, systematic analysis of gene annotation is a powerful tool for interpreting gene expression data, it sometimes is blurred by incomplete gene annotation, missing expression response of key genes and secondary gene expression responses. These shortcomings may be partially circumvented by instead matching gene expression signatures to signatures of other experiments. To facilitate this we present the Functional Association Response by Overlap (FARO) server, that match input signatures to a compendium of 242 gene expression signatures, extracted from more than 1700 Arabidopsis microarray experiments. Hereby we present a publicly available tool for robust characterization of Arabidopsis gene expression experiments which can point to similar experimental factors in other experiments. The server is available at http://www.cbs.dtu.dk/services/faro/.

New Perspectives on the Role of Vitiligo in Immune Responses to Melanoma

PubMed Central

Byrne, Katelyn T.; Turk, Mary Jo

2011-01-01

Melanoma-associated vitiligo is the best-studied example of the linkage between tumor immunity and autoimmunity. Although vitiligo is an independent positive prognostic factor for melanoma patients, the autoimmune destruction of melanocytes was long thought to be merely a side effect of robust anti-tumor immunity. However, new data reveal a key role for vitiligo in supporting T cell responses to melanoma. This research perspective reviews the history of melanoma-associated vitiligo in patients, the experimental studies that form the basis for understanding this relationship, and the unique characteristics of melanoma-specific CD8 T cells found in hosts with vitiligo. We also discuss the implications of our recent findings for the interpretation of patient responses, and the design of next-generation cancer immunotherapies. PMID:21911918

The impact of sound in modern multiline video slot machine play.

PubMed

Dixon, Mike J; Harrigan, Kevin A; Santesso, Diane L; Graydon, Candice; Fugelsang, Jonathan A; Collins, Karen

2014-12-01

Slot machine wins and losses have distinctive, measurable, physiological effects on players. The contributing factors to these effects remain under-explored. We believe that sound is one of these key contributing factors. Sound plays an important role in reinforcement, and thus on arousal level and stress response of players. It is the use of sound for positive reinforcement in particular that we believe influences the player. In the current study, we investigate the role that sound plays in psychophysical responses to slot machine play. A total of 96 gamblers played a slot machine simulator with and without sound being paired with reinforcement. Skin conductance responses and heart rate, as well as subjective judgments about the gambling experience were examined. The results showed that the sound influenced the arousal of participants both psychophysically and psychologically. The sound also influenced players' preferences, with the majority of players preferring to play slot machines that were accompanied by winning sounds. The sounds also caused players to significantly overestimate the number of times they won while playing the slot machine.

Measurement of habituation to noise using the method of continuous judgment by category

NASA Astrophysics Data System (ADS)

Namba, S.; Kuwano, S.

1988-12-01

Using "the method of continuous judgment by category", we examined the noisiness of sounds from public loudspeakers, and habituation to them. Subjects judged the noisiness of the sound at any moment of their choice by touching one of seven numbered keys on a computer keyboard, each corresponding to a noisiness category. At the same time, the subjects were required to complete a task as carefully and rapidly as possible. The duration of "no response" to sounds was an index of habituation. Both personality factors and physical factors were analyzed. It was found that the duration of "no response" is a good index to habituation to noise, and that there were wide differences in the "no response" time of different subjects. The reactions of individual subjects in sessions 1 and 2 and the questionnaire survey were, however, consistent. This suggests that there is a group that is relatively sensitive to noise and a group that is less sensitive to noise. It was also found that subjects had difficulty in becoming accustomed to intense noise.

Colony Stimulating Factor-1 Receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates

PubMed Central

Doloff, Joshua C.; Veiseh, Omid; Vegas, Arturo J.; Tam, Hok Hei; Farah, Shady; Ma, Minglin; Li, Jie; Bader, Andrew; Chiu, Alan; Sadraei, Atieh; Aresta-Dasilva, Stephanie; Griffin, Marissa; Jhunjhunwala, Siddharth; Webber, Matthew; Siebert, Sean; Tang, Katherine; Chen, Michael; Langan, Erin; Dholokia, Nimit; Thakrar, Raj; Qi, Meirigeng; Oberholzer, Jose; Greiner, Dale L.; Langer, Robert; Anderson, Daniel G.

2017-01-01

Host recognition and immune-mediated foreign body response (FBR) to biomaterials can compromise the performance of implanted medical devices. To identify key cell and cytokine targets, here we perform in-depth systems analysis of innate and adaptive immune system responses to implanted biomaterials in rodents and non-human primates. While macrophages are indispensable to the fibrotic cascade, surprisingly neutrophils and complement are not. Macrophages, via CXCL13, lead to downstream B cell recruitment, which further potentiated fibrosis, as confirmed by B cell knock out and CXCL13 neutralization. Interestingly, Colony Stimulating Factor-1 Receptor (CSF1R) is significantly increased following implantation of multiple biomaterial classes: ceramic, polymer, and hydrogel. Its inhibition, like macrophage depletion, leads to complete loss of fibrosis, but spares other macrophage functions such as wound healing, ROS production, and phagocytosis. Our results indicate targeting CSF1R may allow for a more selective method of fibrosis inhibition, and improve biomaterial biocompatibility without the need for broad immunosuppression. PMID:28319612

Toll-like receptor signaling in cell proliferation and survival

PubMed Central

Li, Xinyan; Jiang, Song; Tapping, Richard I.

2009-01-01

Toll-like receptors (TLRs) are important sensors of foreign microbial components as well as products of damaged or inflamed self tissues. Upon sensing these molecules, TLRs initiate a series of downstream signaling events that drive cellular responses including the production of cytokines, chemokines and other inflammatory mediators. This outcome results from the intracellular assembly of protein complexes that drive phosphorylation and other signaling cascades ultimately leading to chromatin remodeling and transcription factor activation. In addition to driving inflammatory responses, TLRs also regulate cell proliferation and survival which serves to expand useful immune cells and integrate inflammatory responses and tissue repair processes. In this context, central TLR signaling molecules, such as the mitogen-activated protein kinases (MAPK) and phosphoinositide 3-kinase (PI3K), play key roles. In addition, four major groups of transcription factors which are targets of TLR activation also control cell fate. This review focuses on the role of TLR signaling as it relates to cell proliferation and survival. This topic not only has important implications for understanding host defense and tissue repair, but also cancer which is often associated with conditions of chronic inflammation. PMID:19775907

Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates

NASA Astrophysics Data System (ADS)

Doloff, Joshua C.; Veiseh, Omid; Vegas, Arturo J.; Tam, Hok Hei; Farah, Shady; Ma, Minglin; Li, Jie; Bader, Andrew; Chiu, Alan; Sadraei, Atieh; Aresta-Dasilva, Stephanie; Griffin, Marissa; Jhunjhunwala, Siddharth; Webber, Matthew; Siebert, Sean; Tang, Katherine; Chen, Michael; Langan, Erin; Dholokia, Nimit; Thakrar, Raj; Qi, Meirigeng; Oberholzer, Jose; Greiner, Dale L.; Langer, Robert; Anderson, Daniel G.

2017-06-01

Host recognition and immune-mediated foreign body response to biomaterials can compromise the performance of implanted medical devices. To identify key cell and cytokine targets, here we perform in-depth systems analysis of innate and adaptive immune system responses to implanted biomaterials in rodents and non-human primates. While macrophages are indispensable to the fibrotic cascade, surprisingly neutrophils and complement are not. Macrophages, via CXCL13, lead to downstream B cell recruitment, which further potentiated fibrosis, as confirmed by B cell knockout and CXCL13 neutralization. Interestingly, colony stimulating factor-1 receptor (CSF1R) is significantly increased following implantation of multiple biomaterial classes: ceramic, polymer and hydrogel. Its inhibition, like macrophage depletion, leads to complete loss of fibrosis, but spares other macrophage functions such as wound healing, reactive oxygen species production and phagocytosis. Our results indicate that targeting CSF1R may allow for a more selective method of fibrosis inhibition, and improve biomaterial biocompatibility without the need for broad immunosuppression.

48 CFR 18.204 - Resources.

Code of Federal Regulations, 2013 CFR

2013-10-01

... response. This key document establishes a comprehensive, national, all-hazards approach to domestic incident response. The Framework identifies the key response principles, roles and structures that organize national response. It describes how communities, States, the Federal Government, the private-sector, and...

48 CFR 18.204 - Resources.

Code of Federal Regulations, 2011 CFR

2011-10-01

... response. This key document establishes a comprehensive, national, all-hazards approach to domestic incident response. The Framework identifies the key response principles, roles and structures that organize national response. It describes how communities, States, the Federal Government, the private-sector, and...

48 CFR 18.204 - Resources.

Code of Federal Regulations, 2014 CFR

2014-10-01

... response. This key document establishes a comprehensive, national, all-hazards approach to domestic incident response. The Framework identifies the key response principles, roles and structures that organize national response. It describes how communities, States, the Federal Government, the private-sector, and...

48 CFR 18.204 - Resources.

Code of Federal Regulations, 2010 CFR

2010-10-01

... response. This key document establishes a comprehensive, national, all-hazards approach to domestic incident response. The Framework identifies the key response principles, roles and structures that organize national response. It describes how communities, States, the Federal Government, the private-sector, and...

48 CFR 18.204 - Resources.

Code of Federal Regulations, 2012 CFR

2012-10-01

... response. This key document establishes a comprehensive, national, all-hazards approach to domestic incident response. The Framework identifies the key response principles, roles and structures that organize national response. It describes how communities, States, the Federal Government, the private-sector, and...

76 FR 26290 - Science Advisory Board Staff Office; Notification of a Public Teleconference of the Chartered...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-06

... report entitled ``SAB Review of EPA's Reanalysis of Key Issues Related to Dioxin Toxicity and Response to... of EPA's Reanalysis of Key Issues Related to Dioxin Toxicity and Response to NAS Comments.'' The SAB... Reanalysis of Key Issues Related to Dioxin Toxicity and Response to NAS Comments.'' To conduct this review...

Exposure to welding fumes activates DNA damage response and redox-sensitive transcription factor signalling in Sprague-Dawley rats.

PubMed

Krishnaraj, Jayaraman; Kowshik, Jaganathan; Sebastian, Robin; Raghavan, Sathees C; Nagini, Siddavaram

2017-05-15

Occupational exposure to welding fumes containing a complex mixture of genotoxic heavy metals, radiation, gases and nanoparticles poses a serious health hazard to welders. Since their categorization as possible carcinogens, welding fumes have gained increasing attention as high priority agents for risk assessment. The present study was undertaken to investigate the effects of welding fume inhalation on oxidative stress, DNA damage response (DDR), and nuclear factor erythroid 2-related factor-2 (Nrf2) and nuclear factor kappa B (NFκB) signalling in the lung tissues of male Sprague-Dawley rats . METHODS: Animals were divided into five groups. Group 1 animals served as control. Rats in groups 2-5 were exposed to 50mg/m 3 stainless steel (SS) welding fumes for 1h for 1day, 1 week, 2 weeks, and 4 weeks respectively. Reactive oxygen species (ROS) generation, 8-oxo-2'-deoxyguanosine (8-oxodG), xenobiotic-metabolizing enzymes (XMEs) and antioxidants were analysed. DNA damage sensors, DNA repair enzymes, inflammatory mediators, cell cycle progression, apoptosis and key players in Nrf2 and NFκB signalling were assessed by flow cytometry, quantitative real-time reverse transcriptase PCR, immunoblotting, immunohistochemistry and immunofluorescence. Rats exposed to welding fumes showed increased levels of chromium and ROS in lung tissues associated with accumulation of 8-oxodG and enhanced expression of XMEs and antioxidants. This was accompanied by upregulation of DNA damage sensors, cell cycle arrest in G1/S phase, overexpression of a multitude of DNA repair enzymes and caspase-mediated apoptosis. In addition, exposure to welding fumes induced activation of Nrf2 and NFκB signalling with enhanced expression of inflammatory mediators. The results of the present study unequivocally demonstrate that exposure of rats to SS welding fumes alters the expression of 37 genes involved in oxidative stress, detoxification, inflammation, DNA repair, cell cycle progression, and apoptosis. Activation of DDR and the ROS-sensitive Nrf2 and NFκB signalling pathways may be key molecular events that mediate adaptive cellular response to welding fume exposure. Copyright © 2017 Elsevier B.V. All rights reserved.