“Everybody Gotta Have a Dream”: Rap-centered Aspirations among Young Black Males Involved in Rap Music Production – A Qualitative Study

PubMed Central

Foster, B. Brian

2015-01-01

Youth express diverse desires for their educational and occupational futures. Sometimes these aspirations are directed towards somewhat unconventional careers such as rapping and other types of involvement in rap music production. Although many studies have examined traditional educational and occupational aspirations, less is known about the factors that give rise to rap-centered aspirations and how individuals pursue them, particularly as they transition to early adulthood. Drawing on 54 semi- and unstructured interviews with 29 black young men involved in rap music production, I find that rap-centered aspirations are shaped by a range of factors, most notably feedback regarding one’s rap skills, access to recording and production equipment, and the financial means to maintain involvement in rap music production while also ensuring personal and family economic stability. The young men in the study attached different meanings to their aspirations and sometimes recast their motivations for participating in rap music production in response to various social and economic factors. PMID:26005703

Cyber Infrastructure Protection

DTIC Science & Technology

2011-05-01

274 TOWARD A SOLUTION THAT WORKS Building on our long history of involvement in assuring all types of communications networks, Tel- cordia has...wireless, and security areas. He currently has responsibility for a new Tel- cordia software product in IP network management, and has led all product

Extended Producer Responsibility and Product Stewardship for Tobacco Product Waste

PubMed Central

Curtis, Clifton; Collins, Susan; Cunningham, Shea; Stigler, Paula; Novotny, Thomas E

2015-01-01

This paper reviews several environmental principles, including Extended Producer Responsibility (EPR), Product Stewardship (PS), the Polluter Pays Principle (PPP), and the Precautionary Principle, as they may apply to tobacco product waste (TPW). The review addresses specific criteria that apply in deciding whether a particular toxic product should adhere to these principles; presents three case studies of similar approaches to other toxic and/or environmentally harmful products; and describes 10 possible interventions or policy actions that may help prevent, reduce, and mitigate the effects of TPW. EPR promotes total lifecycle environmental improvements, placing economic, physical, and informational responsibilities onto the tobacco industry, while PS complements EPR, but with responsibility shared by all parties involved in the tobacco product lifecycle. Both principles focus on toxic source reduction, post-consumer take-back, and final disposal of consumer products. These principles when applied to TPW have the potential to substantially decrease the environmental and public health harms of cigarette butts and other TPW throughout the world. TPW is the most commonly littered item picked up during environmental, urban, and coastal cleanups globally. PMID:26457262

Sensory-motor networks involved in speech production and motor control: an fMRI study.

PubMed

Behroozmand, Roozbeh; Shebek, Rachel; Hansen, Daniel R; Oya, Hiroyuki; Robin, Donald A; Howard, Matthew A; Greenlee, Jeremy D W

2015-04-01

Speaking is one of the most complex motor behaviors developed to facilitate human communication. The underlying neural mechanisms of speech involve sensory-motor interactions that incorporate feedback information for online monitoring and control of produced speech sounds. In the present study, we adopted an auditory feedback pitch perturbation paradigm and combined it with functional magnetic resonance imaging (fMRI) recordings in order to identify brain areas involved in speech production and motor control. Subjects underwent fMRI scanning while they produced a steady vowel sound /a/ (speaking) or listened to the playback of their own vowel production (playback). During each condition, the auditory feedback from vowel production was either normal (no perturbation) or perturbed by an upward (+600 cents) pitch-shift stimulus randomly. Analysis of BOLD responses during speaking (with and without shift) vs. rest revealed activation of a complex network including bilateral superior temporal gyrus (STG), Heschl's gyrus, precentral gyrus, supplementary motor area (SMA), Rolandic operculum, postcentral gyrus and right inferior frontal gyrus (IFG). Performance correlation analysis showed that the subjects produced compensatory vocal responses that significantly correlated with BOLD response increases in bilateral STG and left precentral gyrus. However, during playback, the activation network was limited to cortical auditory areas including bilateral STG and Heschl's gyrus. Moreover, the contrast between speaking vs. playback highlighted a distinct functional network that included bilateral precentral gyrus, SMA, IFG, postcentral gyrus and insula. These findings suggest that speech motor control involves feedback error detection in sensory (e.g. auditory) cortices that subsequently activate motor-related areas for the adjustment of speech parameters during speaking. Copyright © 2015 Elsevier Inc. All rights reserved.

Incorporating risk communication into highly pathogenic avian influenza preparedness and response efforts.

PubMed

Voss, Shauna J; Malladi, Sasidhar; Sampedro, Fernando; Snider, Tim; Goldsmith, Timothy; Hueston, William D; Lauer, Dale C; Halvorson, David A

2012-12-01

A highly pathogenic avian influenza (HPAI) outbreak in the United States will initiate a federal emergency response effort that will consist of disease control and eradication efforts, including quarantine and movement control measures. These movement control measures will not only apply to live animals but also to animal products. However, with current egg industry "just-in-time" production practices, limited storage is available to hold eggs. As a result, stop movement orders can have significant unintended negative consequences, including severe disruptions to the food supply chain. Because stakeholders' perceptions of risk vary, waiting to initiate communication efforts until an HPAI event occurs can hinder disease control efforts, including the willingness of producers to comply with the response, and also can affect consumers' demand for the product. A public-private-academic partnership was formed to assess actual risks involved in the movement of egg industry products during an HPAI event through product specific, proactive risk assessments. The risk analysis process engaged a broad representation of stakeholders and promoted effective risk management and communication strategies before an HPAI outbreak event. This multidisciplinary team used the risk assessments in the development of the United States Department of Agriculture, Highly Pathogenic Avian Influenza Secure Egg Supply Plan, a comprehensive response plan that strives to maintain continuity of business. The collaborative approach that was used demonstrates how a proactive risk communication strategy that involves many different stakeholders can be valuable in the development of a foreign animal disease response plan and build working relationships, trust, and understanding.

Effect of Ethanol on Differential Protein Production and Expression of Potential Virulence Functions in the Opportunistic Pathogen Acinetobacter baumannii

PubMed Central

Nwugo, Chika C.; Arivett, Brock A.; Zimbler, Daniel L.; Gaddy, Jennifer A.; Richards, Ashley M.; Actis, Luis A.

2012-01-01

Acinetobacter baumannii persists in the medical environment and causes severe human nosocomial infections. Previous studies showed that low-level ethanol exposure increases the virulence of A. baumannii ATCC 17978. To better understand the mechanisms involved in this response, 2-D gel electrophoresis combined with mass spectrometry was used to investigate differential protein production in bacteria cultured in the presence or absence of ethanol. This approach showed that the presence of ethanol significantly induces and represses the production of 22 and 12 proteins, respectively. Although over 25% of the ethanol-induced proteins were stress-response related, the overall bacterial viability was uncompromised when cultured under these conditions. Production of proteins involved in lipid and carbohydrate anabolism was increased in the presence of ethanol, a response that correlates with increased carbohydrate biofilm content, enhanced biofilm formation on abiotic surfaces and decrease bacterial motility on semi-solid surfaces. The presence of ethanol also induced the acidification of bacterial cultures and the production of indole-3-acetic acid (IAA), a ubiquitous plant hormone that signals bacterial stress-tolerance and promotes plant-bacteria interactions. These responses could be responsible for the significantly enhanced virulence of A. baumannii ATCC 17978 cells cultured in the presence of ethanol when tested with the Galleria mellonella experimental infection model. Taken together, these observations provide new insights into the effect of ethanol in bacterial virulence. This alcohol predisposes the human host to infections by A. baumannii and could favor the survival and adaptation of this pathogen to medical settings and adverse host environments. PMID:23284824

Effect of ethanol on differential protein production and expression of potential virulence functions in the opportunistic pathogen Acinetobacter baumannii.

PubMed

Nwugo, Chika C; Arivett, Brock A; Zimbler, Daniel L; Gaddy, Jennifer A; Richards, Ashley M; Actis, Luis A

2012-01-01

Acinetobacter baumannii persists in the medical environment and causes severe human nosocomial infections. Previous studies showed that low-level ethanol exposure increases the virulence of A. baumannii ATCC 17978. To better understand the mechanisms involved in this response, 2-D gel electrophoresis combined with mass spectrometry was used to investigate differential protein production in bacteria cultured in the presence or absence of ethanol. This approach showed that the presence of ethanol significantly induces and represses the production of 22 and 12 proteins, respectively. Although over 25% of the ethanol-induced proteins were stress-response related, the overall bacterial viability was uncompromised when cultured under these conditions. Production of proteins involved in lipid and carbohydrate anabolism was increased in the presence of ethanol, a response that correlates with increased carbohydrate biofilm content, enhanced biofilm formation on abiotic surfaces and decrease bacterial motility on semi-solid surfaces. The presence of ethanol also induced the acidification of bacterial cultures and the production of indole-3-acetic acid (IAA), a ubiquitous plant hormone that signals bacterial stress-tolerance and promotes plant-bacteria interactions. These responses could be responsible for the significantly enhanced virulence of A. baumannii ATCC 17978 cells cultured in the presence of ethanol when tested with the Galleria mellonella experimental infection model. Taken together, these observations provide new insights into the effect of ethanol in bacterial virulence. This alcohol predisposes the human host to infections by A. baumannii and could favor the survival and adaptation of this pathogen to medical settings and adverse host environments.

Molecular interactions between the olive and the fruit fly Bactrocera oleae

PubMed Central

2012-01-01

Background The fruit fly Bactrocera oleae is the primary biotic stressor of cultivated olives, causing direct and indirect damages that significantly reduce both the yield and the quality of olive oil. To study the olive-B. oleae interaction, we conducted transcriptomic and proteomic investigations of the molecular response of the drupe. The identifications of genes and proteins involved in the fruit response were performed using a Suppression Subtractive Hybridisation technique and a combined bi-dimensional electrophoresis/nanoLC-ESI-LIT-MS/MS approach, respectively. Results We identified 196 ESTs and 26 protein spots as differentially expressed in olives with larval feeding tunnels. A bioinformatic analysis of the identified non-redundant EST and protein collection indicated that different molecular processes were affected, such as stress response, phytohormone signalling, transcriptional control and primary metabolism, and that a considerable proportion of the ESTs could not be classified. The altered expression of 20 transcripts was also analysed by real-time PCR, and the most striking differences were further confirmed in the fruit of a different olive variety. We also cloned the full-length coding sequences of two genes, Oe-chitinase I and Oe-PR27, and showed that these are wound-inducible genes and activated by B. oleae punctures. Conclusions This study represents the first report that reveals the molecular players and signalling pathways involved in the interaction between the olive fruit and its most damaging biotic stressor. Drupe response is complex, involving genes and proteins involved in photosynthesis as well as in the production of ROS, the activation of different stress response pathways and the production of compounds involved in direct defence against phytophagous larvae. Among the latter, trypsin inhibitors should play a major role in drupe resistance reaction. PMID:22694925

Glycolipid presentation to natural killer T cells differs in an organ-dependent fashion

NASA Astrophysics Data System (ADS)

Schmieg, John; Yang, Guangli; Franck, Richard W.; van Rooijen, Nico; Tsuji, Moriya

2005-01-01

It has been shown that dendritic cells (DCs) are able to present glycolipids to natural killer (NK) T cells in vivo. However, the essential role of DCs, as well as the role of other cells in glycolipid presentation, is unknown. Here, we show that DCs are the crucial antigen-presenting cells (APCs) for splenic NK T cells, whereas Kupffer cells are the key APCs for hepatic NK T cells. Both cell types stimulate cytokine production by NK T cells within 2 h of glycolipid administration, but only DCs are involved in the systemic, downstream responses to glycolipid administration. More specifically, CD8+ DCs produce IL-12 in response to glycolipid presentation, which stimulates secondary IFN- production by NK cells in different organs. Different APCs participate in glycolipid presentation to NK T cells in vivo but differ in their involvement in the overall glycolipid response. dendritic cell | Kupffer cell

Substance misuse prevention as corporate social responsibility.

PubMed

Radacsi, Gergely; Hardi, Peter

2014-03-01

All sectors of society should be involved in reducing substance misuse, including businesses. However, the business sector is typically involved only to the extent that their products compel them to be (e.g., alcohol producers promoting responsible alcohol consumption). This article examines why business participation has been limited and how embedding prevention within a framework of health promotion could increase participation. It reviews both Hungarian and international cases, concluding that although corporate social responsibility (CSR) offers a framework to approach substance misuse reduction, a different perception of the role of the business sector is necessary to make it viable.

Autocrine Regulation of UVA-Induced IL-6 Production via Release of ATP and Activation of P2Y Receptors

PubMed Central

Kawano, Ayumi; Kadomatsu, Remi; Ono, Miyu; Kojima, Shuji; Tsukimoto, Mitsutoshi; Sakamoto, Hikaru

2015-01-01

Extracellular nucleotides, such as ATP, are released from cells in response to various stimuli and act as intercellular signaling molecules through activation of P2 receptors. Exposure to the ultraviolet radiation A (UVA) component of sunlight causes molecular and cellular damage, and in this study, we investigated the involvement of extracellular nucleotides and P2 receptors in the UVA-induced cellular response. Human keratinocyte-derived HaCaT cells were irradiated with a single dose of UVA (2.5 J/cm2), and ATP release and interleukin (IL)-6 production were measured. ATP was released from cells in response to UVA irradiation, and the release was blocked by pretreatment with inhibitors of gap junction hemichannels or P2X7 receptor antagonist. IL-6 production was increased after UVA irradiation, and this increase was inhibited by ecto-nucleotidase or by antagonists of P2Y11 or P2Y13 receptor. These results suggest that UVA-induced IL-6 production is mediated by release of ATP through hemichannels and P2X7 receptor, followed by activation of P2Y11 and P2Y13 receptors. Interestingly, P2Y11 and P2Y13 were associated with the same pattern of IL-6 production, though they trigger different intracellular signaling cascades: Ca2+-dependent and PI3K-dependent, respectively. Thus, IL-6 production in response to UVA-induced ATP release involves at least two distinct pathways, mediated by activation of P2Y11 and P2Y13 receptors. PMID:26030257

Auditory-Nerve Responses to Clicks at Low Levels, and the Initial Peak at High Levels, are Suppressed at Opposite Bias-Tone Phases

NASA Astrophysics Data System (ADS)

Nam, Hui; Guinan, John J.

2011-11-01

Apical auditory nerve (AN) fibers show two click-response regions that are both strongly inhibited by medial olivocochlear (MOC) efferents: (1) ringing responses from low- level (LL) clicks that are thought to be enhanced by a "cochlear amplifier," and (2) AN initial peak (ANIPr) responses from moderate-to-high level (˜70-100 dB pSPL) rarefaction clicks. Since MOC fibers synapse and act on outer hair cells (OHCs), the MOC inhibition of these responses indicates that OHC processes are heavily involved in the production of both LL and ANIPr responses. Using AN recordings in anesthetized cats, we explored the role of OHC stereocilia position in the production of these click-response regions by presenting rarefaction clicks at different phases of 50 Hz, 70-110 dB SPL bias tones. Bias effects on LL responses followed the traditional biasing pattern of twice-a-bias-tone-cycle suppression with more suppression at one phase than the other. This suppression is attributable to the bias tone moving the OHC stereocilia toward low-slope, saturation regions of the mechano-electric transduction function with the rest position being closer to one saturation region. A somewhat similar pattern was found for ANIPr responses except that the bias phases of the largest suppressions were different in ANIPr versus LL responses, usually by ˜180 degrees. The data are consistent with the LL and ANIPr responses both being due to active processes in OHCs that are controlled by OHC stereocilia position. The different phases of the LL and ANIPr suppressions indicate that different mechanisms, and perhaps different vibration patterns in the organ of Corti, are involved in the production of LL and ANIPr responses.

Effect of hot water dips on the quality of fresh-cut ´Ryan Sun´ peaches

USDA-ARS?s Scientific Manuscript database

Fresh-cut products are an important developing food product category, and as a response of current lifestyles they are becoming increasingly popular due to their convenience, nutritious and fresh-like quality; however, fresh-cut produce has limited shelf life because preparation involves physically ...

The construct of food involvement in behavioral research: scale development and validation.

PubMed

Bell, Rick; Marshall, David W

2003-06-01

The construct of involvement has been found to influence brand loyalty, product information search processing, responses to advertising communications, diffusion of innovations, and ultimately, product choice decisions. Traditionally, involvement has been defined as being a characteristic of either a product or of an individual. In the present research, we make an assumption that an individual's 'food involvement' is a somewhat stable characteristic and we hypothesized that involvement with foods would vary between individuals, that individuals who are more highly involved with food would be better able to discriminate between a set of food samples than would less food involved individuals, and that this discrimination would operate both in affective and perceptive relative judgments. Using standard scale construction techniques, we developed a measure of the characteristic of food involvement, based on activities relating to food acquisition, preparation, cooking, eating and disposal. After several iterations, a final 12-item measure was found to have good test-retest reliability and internal consistency within two subscales. A behavioral validation study demonstrated that measures of food involvement were associated with discrimination and hedonic ratings for a range of foods in a laboratory setting. These findings suggest that food involvement, as measured by the Food Involvement Scale, may be an important mediator to consider when undertaking research with food and food habits.

COMPARTMENTALIZATION OF THE INFLAMMATORY RESPONSE TO INHALED GRAIN DUST

EPA Science Inventory

Interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and the secreted form of the IL-1 receptor antagonist (sIL-1RA) are involved in the inflammatory response to inhaled grain dust. Previously, we found considerable production of these cytokines in the lower...

Abstract Graphemic Representations Support Preparation of Handwritten Responses

ERIC Educational Resources Information Center

Shen, Xingjia Rachel; Damian, Marcus F.; Stadthagen-Gonzalez, Hans

2013-01-01

Some evidence suggests that the written production of single words involves not only the ordered retrieval of individual letters, but that abstract, higher-level linguistic properties of the words also influence responses. We report five experiments using the "implicit priming" task adopted from the spoken domain to investigate response…

TLR-2 IS INVOLVED IN AIRWAY EPITHELIAL CELL RESPONE TO AIR POLLUTION PARTICLES

EPA Science Inventory

Primary cultures of normal human airway epithelial cells (NHBE) respond to ambient air pollution particulate matter (PM) by increased production of the cytokine IL-8, and the induction of a number of oxidant stress response genes. Components of ambient air PM responsible for stim...

Elucidating induced plant defenses: the use of targeted metabolomics as a bridge from elicitation to response

USDA-ARS?s Scientific Manuscript database

Dynamic plant defense responses to biotic attack involve the perception of specific biochemical elicitors associated with the offending agent, activation of signaling cascades, and the production of small molecules with complex protective roles. Chemical analyses are essential empirical tools for el...

The regulation of TNFα production after heat and endotoxin stimulation is dependent on Annexin-A1 and HSP70.

PubMed

Nair, Sunitha; Arora, Suruchi; Lim, Jyue Yuan; Lee, Lay Hoon; Lim, Lina H K

2015-07-01

Febrile temperatures can induce stress responses which protect cells from damage and can reduce inflammation during infections and sepsis. However, the mechanisms behind the protective functions of heat in response to the bacterial endotoxin LPS are unclear. We have recently shown that Annexin-1 (ANXA1)-deficient macrophages exhibited higher TNFα levels after LPS stimulation. Moreover, we have previously reported that ANXA1 can function as a stress protein. Therefore in this study, we determined if ANXA1 is involved in the protective effects of heat on cytokine levels in macrophages after heat and LPS. Exposure of macrophages to 42 °C for 1 h prior to LPS results in an inhibition of TNFα production, which was not evident in ANXA1(-/-) macrophages. We show that this regulation involves primarily MYD88-independent pathways. ANXA1 regulates TNFα mRNA stability after heat and LPS, and this is dependent on endogenous ANXA1 expression and not exogenously secreted factors. Further mechanistic studies revealed the possible involvement of the heat shock protein HSP70 and JNK in the heat and inflammatory stress response regulated by ANXA1. This study shows that ANXA1, an immunomodulatory protein, is critical in the heat stress response induced after heat and endotoxin stimulation.

Postprandial glycaemic response: how is it influenced by characteristics of cereal products?

PubMed

Meynier, Alexandra; Goux, Aurélie; Atkinson, Fiona; Brack, Olivier; Vinoy, Sophie

2015-06-28

Cereal products exhibit a wide range of glycaemic indexes (GI), but the interaction of their different nutrients and starch digestibility on blood glucose response is not well known. The objective of this analysis was to evaluate how cereal product characteristics can contribute to GI and insulinaemic index and to the parameters describing glycaemic or insulinaemic responses (incremental AUC, maximum concentration and Δpeak). Moreover, interactions between the different cereal products characteristics and glycaemic response parameters were assessed for the first time. Relationships between the cereal products characteristics and the glycaemic response were analysed by partial least square regressions, followed by modelling. A database including 190 cereal products tested by the usual GI methodology was used. The model on glycaemic responses showed that slowly digestible starch (SDS), rapidly digestible starch (RDS) and fat and fibres, and several interactions involving them, significantly explain GI by 53 % and Δpeak of glycaemia by 60 %. Fat and fibres had important contributions to glycaemic response at low and medium SDS contents in cereal products, but this effect disappears at high SDS levels. We showed also for the first time that glycaemic response parameters are dependent on interactions between starch digestibility (interaction between SDS and RDS) and nutritional composition (interaction between fat and fibres) of the cereal products. We also demonstrated the non-linear effect of fat and fibres (significant effect of their quadratic terms). Hence, optimising both the formula and the manufacturing process of cereal products can improve glucose metabolism, which is recognised as strongly influential on human health.

Optimization of media composition for Nattokinase production by Bacillus subtilis using response surface methodology.

PubMed

Deepak, V; Kalishwaralal, K; Ramkumarpandian, S; Babu, S Venkatesh; Senthilkumar, S R; Sangiliyandi, G

2008-11-01

Response surface methodology and central composite rotary design (CCRD) was employed to optimize a fermentation medium for the production of Nattokinase by Bacillus subtilis at pH 7.5. The four variables involved in this study were Glucose, Peptone, CaCl2, and MgSO4. The statistical analysis of the results showed that, in the range studied; only peptone had a significant effect on Nattokinase production. The optimized medium containing (%) Glucose: 1, Peptone: 5.5, MgSO4: 0.2 and CaCl2: 0.5 resulted in 2-fold increased level of Nattokinase (3194.25U/ml) production compared to initial level (1599.09U/ml) after 10h of fermentation. Nattokinase production was checked with fibrinolytic activity.

Cryptochrome, Phytochrome, and Anthocyanin Production

PubMed Central

Mancinelli, Alberto L.; Rossi, Federica; Moroni, Anna

1991-01-01

Anthocyanin production in cabbage (Brassica oleracea L.) and tomato (Lycopersicon esculentum Mill.) seedlings exposed to prolonged irradiations was studied under conditions that allowed discrimination, within certain limits, between the contribution of cryptochrome and phytochrome in the photoregulation of the response. The results of the study provide confirming evidence for the involvement of cryptochrome and direct evidence for a significant contribution of cryptochrome to the fluence rate dependence of the response to blue. The results provide some preliminary, direct indication for an interaction between cryptochrome and phytochrome in the photoregulation of anthocyanin production in seedlings exposed to the prolonged irradiations required for a high level of expression of the response. The type and degree of interaction between the two photoreceptors vary significantly, depending on the species and experimental conditions. PMID:16668301

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

PubMed Central

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

2016-01-01

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

Molecular cloning of a defense-response-related cytochrome P450 gene from tobacco.

PubMed

Takemoto, D; Hayashi, M; Doke, N; Nishimura, M; Kawakita, K

1999-12-01

Plant defenses against pathogen attack involve a series of inducible responses that contribute to resistance. Tobacco leaves injected with HWC (hyphal wall components prepared from Phytophthora infestans) elicitor showed typical defense responses, including the induction of localized necrosis and the accumulation of pathogenesis-related proteins. In order to elucidate the molecular mechanisms by which plant defense systems are activated, we screened tobacco plants for genes differentially expressed in response to HWC. We performed differential screening by RT-PCR with random primers and obtained PCR products specific to HWC-treated leaf RNA. Northern hybridization using the PCR products as probes confirmed that one transcript was actually induced by HWC treatment. As the deduced amino acid sequence of this clone showed the highest degree of similarity to elicitor-induced soybean cytochrome P450 CYP82A4, it was designated CYP82E1. The expression of CYP82E1 was strongly induced in tobacco by the soybean pathogen Pseudomonas syringae pv. glycinea (nonpathogenic on tobacco), but it was activated only slightly and in a delayed fashion by the tobacco pathogen P. syringae pv. tabaci (pathogenic on tobacco), implying that the product of CYP82E1 may be involved in disease resistance in tobacco.

Evaluation of a co-delivered training package for community mental health professionals on service user- and carer-involved care planning.

PubMed

Grundy, A C; Walker, L; Meade, O; Fraser, C; Cree, L; Bee, P; Lovell, K; Callaghan, P

2017-08-01

WHAT IS KNOWN ON THE SUBJECT?: There is consistent evidence that service users and carers feel marginalized in the process of mental health care planning. Mental health professionals have identified ongoing training needs in relation to involving service users and carers in care planning. There is limited research on the acceptability of training packages for mental health professionals which involve service users and carers as co-facilitators. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: A co-produced and co-delivered training package on service user- and carer-involved care planning was acceptable to mental health professionals. Aspects of the training that were particularly valued were the co-production model, small group discussion and the opportunity for reflective practice. The organizational context of care planning may need more consideration in future training models. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health nurses using co-production models of delivering training to other mental health professionals can be confident that such initiatives will be warmly welcomed, acceptable and engaging. On the basis of the results reported here, we encourage mental health nurses to use co-production approaches more often. Further research will show how clinically effective this training is in improving outcomes for service users and carers. Background There is limited evidence for the acceptability of training for mental health professionals on service user- and carer-involved care planning. Aim To investigate the acceptability of a co-delivered, two-day training intervention on service user- and carer-involved care planning. Methods Community mental health professionals were invited to complete the Training Acceptability Rating Scale post-training. Responses to the quantitative items were summarized using descriptive statistics (Miles, ), and qualitative responses were coded using content analysis (Weber, ). Results Of 350 trainees, 310 completed the questionnaire. The trainees rated the training favourably (median overall TARS scores = 56/63; median 'acceptability' score = 34/36; median 'perceived impact' score = 22/27). There were six qualitative themes: the value of the co-production model; time to reflect on practice; delivery preferences; comprehensiveness of content; need to consider organizational context; and emotional response. Discussion The training was found to be acceptable and comprehensive with participants valuing the co-production model. Individual differences were apparent in terms of delivery preferences and emotional reactions. There may be a need to further address the organizational context of care planning in future training. Implications for practice Mental health nurses should use co-production models of continuing professional development training that involve service users and carers as co-facilitators. © 2017 The Authors. Journal of Psychiatric and Mental Health Nursing Published by John Wiley & Sons Ltd.

Sexual Orientation as a Peripheral Cue in Advertising: Effects of Models' Sexual Orientation, Argument Strength, and Involvement on Responses to Magazine Ads.

PubMed

Ivory, Adrienne Holz

2017-10-12

This study examines how sexual orientation of couples featured in magazine advertisements affects heterosexual viewers' responses using the elaboration likelihood model as a framework. A 3 × 2 × 2 × 3 experiment tested effects of sexual orientation, argument strength, involvement, and attitudes toward homosexuality on heterosexuals' attitudes toward the couple, advertisement, brand, and product, purchase intentions, and recall. Results indicate that consumers were accepting of ads with lesbian portrayals. Participants showed more negative attitudes toward gay male portrayals, but attitudes toward heterosexual and lesbian ads were similar. This effect was moderated by participants' attitudes toward homosexuals. Low-involvement consumers showed more negative attitudes toward homosexual portrayals than toward heterosexual portrayals, indicating that sexual orientation may have served as a peripheral cue negatively impacting attitudes toward the couple and ad under low elaboration. These effects were not observed for attitudes toward the brand and product, purchase intentions, or recall.

Choosing an Angle: Citizenship through Video Production

ERIC Educational Resources Information Center

Verrall, Ben

2006-01-01

Citizenship education is an important part of the development of young adults, enabling them to learn about their rights and responsibilities, and to understand how society works. Video is an effective medium for young people to express their views and, through involvement in a production process, they are able to learn more about putting forward…

Neural Responses to the Production and Comprehension of Syntax in Identical Utterances

ERIC Educational Resources Information Center

Indefrey, Peter; Hellwig, Frauke; Herzog, Hans; Seitz, Rudiger J.; Hagoort, Peter

2004-01-01

Following up on an earlier positron emission tomography (PET) experiment (Indefrey et al., 2001), we used a scene description paradigm to investigate whether a posterior inferior frontal region subserving syntactic encoding for speaking is also involved in syntactic parsing during listening. In the language production part of the experiment,…

Adult Education in a Workplace Context: Recognising Production Workers' Responses and Partnership Challenges

ERIC Educational Resources Information Center

Wärvik, Gun-Britt

2016-01-01

This article is about a larger regional Swedish partnership programme that was established to develop site-based education for production workers. A partnership is seen as composed of different practice architectures. The actors involved represented larger transnational as well as smaller manufacturing companies, employers, the metal workers'…

Establishing Documentary Production Support for 21st Century Campuses

ERIC Educational Resources Information Center

Davison, Elizabeth L.; Hansell, Thomas S.

2014-01-01

As a response to the growing trend of academic assignments that involve some type of video production, this paper advocates that campuses need to provide instructional as well as technical support for such projects. Universities invest in writing centers to help cultivate writing skills because they understand that providing the latest word…

The Cell Wall Integrity Signaling Pathway and Its Involvement in Secondary Metabolite Production.

PubMed

Valiante, Vito

2017-12-06

The fungal cell wall is the external and first layer that fungi use to interact with the environment. Every stress signal, before being translated into an appropriate stress response, needs to overtake this layer. Many signaling pathways are involved in translating stress signals, but the cell wall integrity (CWI) signaling pathway is the one responsible for the maintenance and biosynthesis of the fungal cell wall. In fungi, the CWI signal is composed of a mitogen-activated protein kinase (MAPK) module. After the start of the phosphorylation cascade, the CWI signal induces the expression of cell-wall-related genes. However, the function of the CWI signal is not merely the activation of cell wall biosynthesis, but also the regulation of expression and production of specific molecules that are used by fungi to better compete in the environment. These molecules are normally defined as secondary metabolites or natural products. This review is focused on secondary metabolites affected by the CWI signal pathway with a special focus on relevant natural products such as melanins, mycotoxins, and antibacterial compounds.

The potential mechanism of Bursal-derived BPP-II on the antibody production and avian pre-B cell.

PubMed

Feng, Xiuli; Cao, Ruibing; Zhou, Bin; Liu, Qingtao; Liu, Ke; Liu, Xiaodong; Zhang, Yuanpeng; Gu, Jinyan; Miao, Denian; Chen, Puyan

2013-03-01

The bursa of Fabricius is critical for the normal development of the B lymphocytes responsible for antibody production. However, the mechanism of the bursal-derived bioactive factor on B cell development is little reported. In this paper, chicks were immunized with BPP-II and AIV vaccine or AIV antigen, and antibody and IL-4 production were detected. The results showed that BPP-II played strongly inducing roles on the humoral immune responses. To investigate the gene expression at transcriptional level, avian pre-B lymphocyte DT40 cells were treated with BPP-II, and were analyzed with the gene microarray. The results proved that BPP-II treatment regulated 11 pathways, in which homologous recombination is a vital mechanism which is involved in antibody Ig gene conversion and diversification during B cell development. These results suggested Bursal-derived biological active factor BPP-II might be involved in the antibody production processes and B cell development, which is vital to the humoral central immune organ, the bursa of Fabricius. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cryptochrome 2 expression level is critical for adrenocorticotropin stimulation of cortisol production in the capuchin monkey adrenal.

PubMed

Torres-Farfan, C; Abarzua-Catalan, L; Valenzuela, F J; Mendez, N; Richter, H G; Valenzuela, G J; Serón-Ferré, M

2009-06-01

Timely production of glucocorticoid hormones in response to ACTH is essential for survival by coordinating energy intake and expenditure and acting as homeostatic regulators against stress. Adrenal cortisol response to ACTH is clock time dependent, suggesting that an intrinsic circadian oscillator in the adrenal cortex contributes to modulate the response to ACTH. Circadian clock gene expression has been reported in the adrenal cortex of several species. However, there are no reports accounting for potential involvement of adrenal clock proteins on cortisol response to ACTH. Here we explored whether the clock protein cryptochrome 2 (CRY2) knockdown modifies the adrenal response to ACTH in a primate. Adrenal gland explants from adult capuchin monkey (n = 5) were preincubated for 6 h with transfection vehicle (control) or with two different Cry2 antisense and sense probes followed by 48 h incubation in medium alone (no ACTH) or with 100 nm ACTH. Under control and sense conditions, ACTH increased cortisol production, whereas CRY2 suppression inhibited ACTH-stimulated cortisol production. Expression of the steroidogenic enzymes steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase at 48 h of incubation was increased by ACTH in control explants and suppressed by Cry2 knockdown. Additionally, we found that Cry2 knockdown decreased the expression of the clock gene brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (Bmal1) at the mRNA and protein levels. Altogether these results strongly support that the clock protein CRY2 is involved in the mechanism by which ACTH increases the expression of steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase. Thus, adequate expression levels of components of the adrenal circadian clock are required for an appropriate cortisol response to ACTH.

The RING finger E3 ligase STRF1 is involved in membrane trafficking and modulates salt-stress response in Arabidopsis thaliana.

PubMed

Tian, Miaomiao; Lou, Lijuan; Liu, Lijing; Yu, Feifei; Zhao, Qingzhen; Zhang, Huawei; Wu, Yaorong; Tang, Sanyuan; Xia, Ran; Zhu, Baoge; Serino, Giovanna; Xie, Qi

2015-04-01

Salt stress is a detrimental factor for plant growth and development. The response to salt stress has been shown to involve components in the intracellular trafficking system, as well as components of the ubiquitin-proteasome system (UPS). In this article, we have identified in Arabidopsis thaliana a little reported ubiquitin ligase involved in salt-stress response, which we named STRF1 (Salt Tolerance RING Finger 1). STRF1 is a member of RING-H2 finger proteins and we demonstrate that it has ubiquitin ligase activity in vitro. We also show that STRF1 localizes mainly at the plasma membrane and at the intracellular endosomes. strf1-1 loss-of-function mutant seedlings exhibit accelerated endocytosis in roots, and have altered expression of several genes involved in the membrane trafficking system. Moreover, protein trafficking inhibitor, brefeldin A (BFA), treatment has increased BFA bodies in strf1-1 mutant. This mutant also showed increased tolerance to salt, ionic and osmotic stresses, reduced accumulation of reactive oxygen species during salt stress, and increased expression of AtRbohD, which encodes a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase involved in H2 O2 production. We conclude that STRF1 is a membrane trafficking-related ubiquitin ligase, which helps the plant to respond to salt stress by monitoring intracellular membrane trafficking and reactive oxygen species (ROS) production. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Human-Centred Design Projects and Co-Design in/outside the Turkish Classroom: Responses and Challenges

ERIC Educational Resources Information Center

Emmanouil, Marina

2015-01-01

Perhaps more than any other professional group in modern history, designers have felt compelled to undertake the responsibility of addressing and engaging with societal problems in their practice. Initially, this liability involved concerns of form and production methods during the industrial revolution era, and developed into existential, ethical…

Applying Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks to link toxicity testing data to exposure-relevant and biologically-relevant responses

EPA Science Inventory

Hazard assessment for nanomaterials often involves applying in vitro dose-response data to estimate potential health risks that arise from exposure to products that contain nanomaterials. However, much uncertainty is inherent in relating bioactivities observed in an in vitro syst...

Nitric oxide production by hemocytes of the ascidian Styela plicata.

PubMed

de Barros, Cintia Monteiro; de Carvalho, Danielle Ronald; Andrade, Leonardo R; Pavão, Mauro Sérgio G; Allodi, Silvana

2009-10-01

Ascidian hemolymph contains various types of blood cells (hemocytes), which are believed to be involved in defense mechanisms. We have studied nitric-oxide (NO) synthase activity in hemocytes of the ascidian Styela plicata after exposure to lipopolysaccharide (LPS). To investigate which cell types are involved in NO production, we first identified, by electron microscopy, the types of hemocytes previously described, mainly by light microscopy, by others. Five types of blood cells could be recognized in the hemolymph: granulocytes, hemoblasts, lymphocyte-like cells, morula cells, and pigment cells. The lymphocyte-like cells produced the most NO. In agreement with studies of other invertebrates, nitrite generation did not change after LPS stimulation in assays in vitro, under either different concentrations of LPS or different time periods. Therefore, we performed an in vivo assay by injecting a known quantity of Escherichia coli into the tunic of the ascidians in order to investigate possible differences in NO levels. No increase of NO occurred accompanying the inflammatory reaction suggesting that another molecule in the pathway was involved. We found that nuclear factor kappaB (NFkappaB) was activated. Since NFkappaB is involved in the production of many substances related to immune responses, additional molecules might also be generated in response to E. coli infection. These observations may improve our understanding of the reaction of animals to eutrophic conditions.

Involvement of Lipocalin-like CghA in Decalin-Forming Stereoselective Intramolecular [4+2] Cycloaddition

PubMed Central

Sato, Michio; Yagishita, Fumitoshi; Mino, Takashi; Uchiyama, Nahoko; Patel, Ashay; Chooi, Yit-Heng; Goda, Yukihiro; Xu, Wei; Noguchi, Hiroshi; Yamamoto, Tsuyoshi; Hotta, Kinya; Houk, Kendall N.; Tang, Yi

2016-01-01

Understanding enzymatic Diels—Alder (DA) reactions that can form complex natural product scaffold is of considerable interest. Sch 210972 1, a potential anti-HIV fungal natural product, contains a decalin core that is proposed to form via a DA reaction. We identified the gene cluster responsible for the biosynthesis of 1 and heterologously reconstituted the biosynthetic pathway in Aspergillus nidulans to characterize the enzymes involved. Most notably, deletion of cghA resulted in a loss of stereoselective decalin core formation, yielding both an endo 1 and a diastereomeric exo adducts of the proposed DA reaction. Complementation with cghA restored the sole formation of 1. Density functional theory computation of the proposed DA reaction provided a plausible explanation of the observed pattern of product formation. Based on our study, we propose that lipocalin-like CghA is responsible for the stereoselective intramolecular [4+2] cycloaddition that forms the decalin core of 1. PMID:26360642

The Influence of MHC and Immunoglobulins A and E on Host Resistance to Gastrointestinal Nematodes in Sheep

PubMed Central

Lee, C. Y.; Munyard, K. A.; Gregg, K.; Wetherall, J. D.; Stear, M. J.; Groth, D. M.

2011-01-01

Gastrointestinal nematode parasites in farmed animals are of particular importance due to their effects on production. In Australia, it is estimated that the direct and indirect effects of parasite infestation cost the animal production industries hundreds of millions of dollars each year. The main factors considered by immunologists when studying gastrointestinal nematode infections are the effects the host's response has on the parasite, which immunological components are responsible for these effects, genetic factors involved in controlling immunological responses, and the interactions between these forming an interconnecting multilevel relationship. In this paper, we describe the roles of immunoglobulins, in particular IgA and IgE, and the major histocompatibility complex in resistance to gastrointestinal parasites in sheep. We also draw evidence from other animal models to support the involvement of these immune components. Finally, we examine how IgA and IgE exert their influence and how methods may be developed to manage susceptible animals. PMID:21584228

The Role of Sustained Attention in the Production of Conjoined Noun Phrases: An Individual Differences Study.

PubMed

Jongman, Suzanne R; Meyer, Antje S; Roelofs, Ardi

2015-01-01

It has previously been shown that language production, performed simultaneously with a nonlinguistic task, involves sustained attention. Sustained attention concerns the ability to maintain alertness over time. Here, we aimed to replicate the previous finding by showing that individuals call upon sustained attention when they plan single noun phrases (e.g., "the carrot") and perform a manual arrow categorization task. In addition, we investigated whether speakers also recruit sustained attention when they produce conjoined noun phrases (e.g., "the carrot and the bucket") describing two pictures, that is, when both the first and second task are linguistic. We found that sustained attention correlated with the proportion of abnormally slow phrase-production responses. Individuals with poor sustained attention displayed a greater number of very slow responses than individuals with better sustained attention. Importantly, this relationship was obtained both for the production of single phrases while performing a nonlinguistic manual task, and the production of noun phrase conjunctions in referring to two spatially separated objects. Inhibition and updating abilities were also measured. These scores did not correlate with our measure of sustained attention, suggesting that sustained attention and executive control are distinct. Overall, the results suggest that planning conjoined noun phrases involves sustained attention, and that language production happens less automatically than has often been assumed.

A probiotic dairy product containing L. gasseri CECT5714 and L. coryniformis CECT5711 induces immunological changes in children suffering from allergy.

PubMed

Martínez-Cañavate, Ana; Sierra, Saleta; Lara-Villoslada, Federico; Romero, Julio; Maldonado, José; Boza, Julio; Xaus, Jordi; Olivares, Mónica

2009-09-01

The increase in the prevalence of allergic diseases in children has been attributed to an unbalanced immune response probably due to environmental factors. The immunoregulatory properties of probiotic bacteria could balance the disequilibrium in the immune response causing the allergic response. The aim of this study was to evaluate the immunological effects of the consumption of a dairy product containing two probiotic strains in children suffering from allergy. A double-blinded, randomized, control comparative study was performed with 44 allergic children. Children were randomly distributed in two groups, a control Yogurt and a Probiotic group. Both groups daily consumed 200 ml of a dairy fermented product for 3 months. The Yogurt group consumed a conventional yogurt, whereas the Probiotic group consumed a similar dairy product where Lactobacillus bulgaricus was substituted by a mixture of Lactobacillus gasseri CECT5714 and Lactobacillus coryniformis CECT5711 (at least 10(6) cfu/g each strain). Intestinal and immunological parameters were measured in fecal and blood samples. The consumption of the probiotic product induced a significant decrease in the level of IgE in plasma (p = 0.03) and an increase in CD4(+)/CD25(+) T regulatory cells (p = 0.01). The decrease in IgE was accompanied by a significant increase in mucosal IgA (p = 0.01). However, changes in other effector cells potentially involved in allergic reactions such as eosinophiles, basophiles or other IgE+ cells were not detected. The consumption of the probiotic product also induced significant changes in innate response as a significant increase in natural killer cells was detected (p = 0.03). The daily consumption of a probiotic product containing L. gasseri CECT5714 and L. coryniformis CECT5711 for 3 months induces, in allergic children, beneficial effects on immune parameters involved in the allergic response such as a reduction of IgE in plasma and an increase in regulatory T cells. The probiotic product also enhanced innate and specific immune parameters that may improve the general health status of children.

An S-Type Anion Channel SLAC1 Is Involved in Cryptogein-Induced Ion Fluxes and Modulates Hypersensitive Responses in Tobacco BY-2 Cells

PubMed Central

Horikoshi, Sonoko; Hanamata, Shigeru; Negi, Juntaro; Yagi, Chikako; Kitahata, Nobutaka; Iba, Koh; Kuchitsu, Kazuyuki

2013-01-01

Pharmacological evidence suggests that anion channel-mediated plasma membrane anion effluxes are crucial in early defense signaling to induce immune responses and hypersensitive cell death in plants. However, their molecular bases and regulation remain largely unknown. We overexpressed Arabidopsis SLAC1, an S-type anion channel involved in stomatal closure, in cultured tobacco BY-2 cells and analyzed the effect on cryptogein-induced defense responses including fluxes of Cl− and other ions, production of reactive oxygen species (ROS), gene expression and hypersensitive responses. The SLAC1-GFP fusion protein was localized at the plasma membrane in BY-2 cells. Overexpression of SLAC1 enhanced cryptogein-induced Cl− efflux and extracellular alkalinization as well as rapid/transient and slow/prolonged phases of NADPH oxidase-mediated ROS production, which was suppressed by an anion channel inhibitor, DIDS. The overexpressor also showed enhanced sensitivity to cryptogein to induce downstream immune responses, including the induction of defense marker genes and the hypersensitive cell death. These results suggest that SLAC1 expressed in BY-2 cells mediates cryptogein-induced plasma membrane Cl− efflux to positively modulate the elicitor-triggered activation of other ion fluxes, ROS as well as a wide range of defense signaling pathways. These findings shed light on the possible involvement of the SLAC/SLAH family anion channels in cryptogein signaling to trigger the plasma membrane ion channel cascade in the plant defense signal transduction network. PMID:23950973

An S-type anion channel SLAC1 is involved in cryptogein-induced ion fluxes and modulates hypersensitive responses in tobacco BY-2 cells.

PubMed

Kurusu, Takamitsu; Saito, Katsunori; Horikoshi, Sonoko; Hanamata, Shigeru; Negi, Juntaro; Yagi, Chikako; Kitahata, Nobutaka; Iba, Koh; Kuchitsu, Kazuyuki

2013-01-01

Pharmacological evidence suggests that anion channel-mediated plasma membrane anion effluxes are crucial in early defense signaling to induce immune responses and hypersensitive cell death in plants. However, their molecular bases and regulation remain largely unknown. We overexpressed Arabidopsis SLAC1, an S-type anion channel involved in stomatal closure, in cultured tobacco BY-2 cells and analyzed the effect on cryptogein-induced defense responses including fluxes of Cl(-) and other ions, production of reactive oxygen species (ROS), gene expression and hypersensitive responses. The SLAC1-GFP fusion protein was localized at the plasma membrane in BY-2 cells. Overexpression of SLAC1 enhanced cryptogein-induced Cl(-) efflux and extracellular alkalinization as well as rapid/transient and slow/prolonged phases of NADPH oxidase-mediated ROS production, which was suppressed by an anion channel inhibitor, DIDS. The overexpressor also showed enhanced sensitivity to cryptogein to induce downstream immune responses, including the induction of defense marker genes and the hypersensitive cell death. These results suggest that SLAC1 expressed in BY-2 cells mediates cryptogein-induced plasma membrane Cl(-) efflux to positively modulate the elicitor-triggered activation of other ion fluxes, ROS as well as a wide range of defense signaling pathways. These findings shed light on the possible involvement of the SLAC/SLAH family anion channels in cryptogein signaling to trigger the plasma membrane ion channel cascade in the plant defense signal transduction network.

Cortisol Induces Reactive Oxygen Species Through a Membrane Glucocorticoid Receptor in Rainbow Trout Myotubes.

PubMed

Espinoza, Marlen B; Aedo, Jorge E; Zuloaga, Rodrigo; Valenzuela, Cristian; Molina, Alfredo; Valdés, Juan A

2017-04-01

Cortisol is an essential regulator of neuroendocrine stress responses in teleosts. Cortisol predominantly affects target tissues through the genomic pathway, which involves interacting with cytoplasmic glucocorticoid receptors, and thereby, modulating stress-response gene expressions. Cortisol also produces rapid effects via non-genomic pathways, which do not involve gene transcription. Although cortisol-mediated genomic pathways are well documented in teleosts, non-genomic pathways are not fully understood. Moreover, no studies have focused on the contribution of non-genomic cortisol pathways in compensatory stress responses in fish. In this study, rainbow trout (Oncorhynchus mykiss) skeletal myotubes were stimulated with physiological concentrations of cortisol and cortisol-BSA, a membrane-impermeable agent, resulting in an early induction of reactive oxygen species (ROS). This production was not suppressed by transcription or translation inhibitors, suggesting non-genomic pathway involvement. Moreover, myotube preincubation with RU486 and NAC completely suppressed cortisol- and cortisol-BSA-induced ROS production. Subcellular fractionation analysis revealed the presence of cell membrane glucocorticoid receptors. Finally, cortisol-BSA induced a significant increase in ERK1/2 and CREB phosphorylation, as well as in CREB-dependent transcriptional activation of the pgc1a gene expression. The obtained results strongly suggest that cortisol acts through a non-genomic glucocorticoid receptor-mediated pathway to induce ROS production and contribute to ERK/CREB/PGC1-α signaling pathway activation as stress compensation mechanisms. J. Cell. Biochem. 118: 718-725, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Reconstitution of a fungal meroterpenoid biosynthesis reveals the involvement of a novel family of terpene cyclases

NASA Astrophysics Data System (ADS)

Itoh, Takayuki; Tokunaga, Kinya; Matsuda, Yudai; Fujii, Isao; Abe, Ikuro; Ebizuka, Yutaka; Kushiro, Tetsuo

2010-10-01

Meroterpenoids are hybrid natural products of both terpenoid and polyketide origin. We identified a biosynthetic gene cluster that is responsible for the production of the meroterpenoid pyripyropene in the fungus Aspergillus fumigatus through reconstituted biosynthesis of up to five steps in a heterologous fungal expression system. The cluster revealed a previously unknown terpene cyclase with an unusual sequence and protein primary structure. The wide occurrence of this sequence in other meroterpenoid and indole-diterpene biosynthetic gene clusters indicates the involvement of these enzymes in the biosynthesis of various terpenoid-bearing metabolites produced by fungi and bacteria. In addition, a novel polyketide synthase that incorporated nicotinyl-CoA as the starter unit and a prenyltransferase, similar to that in ubiquinone biosynthesis, was found to be involved in the pyripyropene biosynthesis. The successful production of a pyripyropene analogue illustrates the catalytic versatility of these enzymes for the production of novel analogues with useful biological activities.

In Vitro Optimization of Enzymes Involved in Precorrin-2 Synthesis Using Response Surface Methodology.

PubMed

Fang, Huan; Dong, Huina; Cai, Tao; Zheng, Ping; Li, Haixing; Zhang, Dawei; Sun, Jibin

2016-01-01

In order to maximize the production of biologically-derived chemicals, kinetic analyses are first necessary for predicting the role of enzyme components and coordinating enzymes in the same reaction system. Precorrin-2 is a key precursor of cobalamin and siroheme synthesis. In this study, we sought to optimize the concentrations of several molecules involved in precorrin-2 synthesis in vitro: porphobilinogen synthase (PBGS), porphobilinogen deaminase (PBGD), uroporphyrinogen III synthase (UROS), and S-adenosyl-l-methionine-dependent urogen III methyltransferase (SUMT). Response surface methodology was applied to develop a kinetic model designed to maximize precorrin-2 productivity. The optimal molar ratios of PBGS, PBGD, UROS, and SUMT were found to be approximately 1:7:7:34, respectively. Maximum precorrin-2 production was achieved at 0.1966 ± 0.0028 μM/min, agreeing with the kinetic model's predicted value of 0.1950 μM/min. The optimal concentrations of the cofactor S-adenosyl-L-methionine (SAM) and substrate 5-aminolevulinic acid (ALA) were also determined to be 200 μM and 5 mM, respectively, in a tandem-enzyme assay. By optimizing the relative concentrations of these enzymes, we were able to minimize the effects of substrate inhibition and feedback inhibition by S-adenosylhomocysteine on SUMT and thereby increase the production of precorrin-2 by approximately five-fold. These results demonstrate the effectiveness of kinetic modeling via response surface methodology for maximizing the production of biologically-derived chemicals.

Cadmium-Induced Hydrogen Sulfide Synthesis Is Involved in Cadmium Tolerance in Medicago sativa by Reestablishment of Reduced (Homo)glutathione and Reactive Oxygen Species Homeostases

PubMed Central

Cui, Weiti; Chen, Huiping; Zhu, Kaikai; Jin, Qijiang; Xie, Yanjie; Cui, Jin; Xia, Yan; Zhang, Jing; Shen, Wenbiao

2014-01-01

Until now, physiological mechanisms and downstream targets responsible for the cadmium (Cd) tolerance mediated by endogenous hydrogen sulfide (H2S) have been elusive. To address this gap, a combination of pharmacological, histochemical, biochemical and molecular approaches was applied. The perturbation of reduced (homo)glutathione homeostasis and increased H2S production as well as the activation of two H2S-synthetic enzymes activities, including L-cysteine desulfhydrase (LCD) and D-cysteine desulfhydrase (DCD), in alfalfa seedling roots were early responses to the exposure of Cd. The application of H2S donor sodium hydrosulfide (NaHS), not only mimicked intracellular H2S production triggered by Cd, but also alleviated Cd toxicity in a H2S-dependent fashion. By contrast, the inhibition of H2S production caused by the application of its synthetic inhibitor blocked NaHS-induced Cd tolerance, and destroyed reduced (homo)glutathione and reactive oxygen species (ROS) homeostases. Above mentioned inhibitory responses were further rescued by exogenously applied glutathione (GSH). Meanwhile, NaHS responses were sensitive to a (homo)glutathione synthetic inhibitor, but reversed by the cotreatment with GSH. The possible involvement of cyclic AMP (cAMP) signaling in NaHS responses was also suggested. In summary, LCD/DCD-mediated H2S might be an important signaling molecule in the enhancement of Cd toxicity in alfalfa seedlings mainly by governing reduced (homo)glutathione and ROS homeostases. PMID:25275379

The pulmonary neuroendocrine system and drainage of the fetal lung: effects of serotonin.

PubMed

Chua, B A; Perks, A M

1999-03-01

The neuroendocrine system of the lungs is maximally developed and activated at birth, but has no clear function. Here, one of its products, serotonin, was tested for an ability to stop lung fluid production or activate reabsorption. Lungs from fetal guinea pigs (61 +/- 2 days of gestation) were supported in vitro for 3 h; lung liquid production was monitored by a dye dilution method. Initial studies on 36 young fetuses (61 +/- 1 days of gestation) showed that untreated controls produced fluid at 1.17 +/- 0.23 ml.kg-1.h-1, with no significant change over 3 h (ANOVA; regression analysis); those given 10(-8) M serotonin during the middle hour showed no significant changes, but those given 5 x 10(-8), 10(-7), 10(-6), or 10(-5) M serotonin reduced production significantly (P < 0.01 to P < 0.0005). Responses were linear up to 10(-7) M (threshold, 10(-9) M) and then become maximal at 50% reduction. However, responses increased with age. Comparison of 40 fetuses divided into groups of 60-61 or 65-67 days of gestation showed a large and significant increase in responses in the older fetuses (P < 0.01), where half the preparations reabsorbed fluid. Serotonin receptors were involved, since 10(-6) M cyproheptadine abolished responses (based on 24 preparations). Amiloride-sensitive Na+ channels were involved, since 10(-6) M amiloride abolished responses (based on 24 preparations). These results, in combination with earlier results from somatostatin and dopamine, together with histochemical and clinical observations, strongly suggest that the neuroendocrine system of the lungs may find a function in clearing fluid from the lungs at time of birth. Copyright 1999 Academic Press.

Immune Response to Electromagnetic Fields through Cybernetic Modeling

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

Godina-Nava, J. J.; Segura, M. A. Rodriguez; Cadena, S. Reyes

We study the optimality of the humoral immune response through a mathematical model, which involves the effect of electromagnetic fields over the large lymphocytes proliferation. Are used the so called cybernetic variables in the context of the matching law of microeconomics or mathematical psychology, to measure the large lymphocytes population and to maximize the instantaneous antibody production rate in time during the immunologic response in order to most efficiently inactivate the antigen.

Immune Response to Electromagnetic Fields through Cybernetic Modeling

NASA Astrophysics Data System (ADS)

Godina-Nava, J. J.; Segura, M. A. Rodríguez; Cadena, S. Reyes; Sierra, L. C. Gaitán

2008-08-01

We study the optimality of the humoral immune response through a mathematical model, which involves the effect of electromagnetic fields over the large lymphocytes proliferation. Are used the so called cybernetic variables in the context of the matching law of microeconomics or mathematical psychology, to measure the large lymphocytes population and to maximize the instantaneous antibody production rate in time during the immunologic response in order to most efficiently inactivate the antigen.

Mycobacterium tuberculosis toxin Rv2872 is an RNase involved in vancomycin stress response and biofilm development.

PubMed

Wang, Xiaoyu; Zhao, Xiaokang; Wang, Hao; Huang, Xue; Duan, Xiangke; Gu, Yinzhong; Lambert, Nzungize; Zhang, Ke; Kou, Zhenhao; Xie, Jianping

2018-06-11

Bacterial toxin-antitoxin (TA) systems are emerging important regulators of multiple cellular physiological events and candidates for novel antibiotic targets. To explore the role of Mycobacterium tuberculosis function, unknown toxin gene Rv2872 was heterologously expressed in Mycobacterium smegmatis (MS_Rv2872). Upon induction, MS_Rv2872 phenotype differed significantly from the control, such as increased vancomycin resistance, retarded growth, cell wall, and biofilm structure. This phenotype change might result from the RNase activity of Rv2872 as purified Rv2872 toxin protein can cleave the products of several key genes involved in abovementioned phenotypes. In summary, toxin Rv2872 was firstly reported to be a endonuclease involved in antibiotic stress responses, cell wall structure, and biofilm development.

The immunomodulatory effects of interferon-gamma on mature B-lymphocyte responses.

PubMed

Jurado, A; Carballido, J; Griffel, H; Hochkeppel, H K; Wetzel, G D

1989-06-15

Interferon-gamma (IFN-gamma) exerts a broad spectrum of activities which affect the responses of mature B-cells. It strongly inhibits B-cell activation, acts as a B-cell growth factor (BCGF), and also induces final differentiation to immunoglobulin (Ig) production. IFN-gamma is deeply involved in the differential control of isotype expression, as it enhances IgG2a production and suppresses both IgG1 and IgE production. Although it is now possible to draw a general scheme of the effects of IFN-gamma on B-cells, a number of paradoxical results still exist in the field. In this manuscript, different experimental systems are analyzed in an attempt to explain these apparent paradoxes.

Production of pure protein antibodies and development of immunoassays to detect Ara h 3 levels in peanut varieties.

USDA-ARS?s Scientific Manuscript database

Peanuts are one of the most allergenic foods, and are widespread in western food products; therefore, there has been intense research into the allergic nature of the proteins involved. Ara h 3 is one of three immunodominant allergenic proteins responsible. It is a 60 kDa protein which forms follow...

Neutrophils differentially attenuate immune response to Aspergillus infection through complement receptor 3 and induction of myeloperoxidase.

PubMed

Goh, Jessamine G; Ravikumar, Sharada; Win, Mar Soe; Cao, Qiong; Tan, Ai Ling; Lim, Joan H J; Leong, Winnie; Herbrecht, Raoul; Troke, Peter F; Kullberg, Bart Jan; Netea, Mihai G; Chng, Wee Joo; Dan, Yock Young; Chai, Louis Y A

2018-03-01

Invasive aspergillosis (IA) remains a major cause of morbidity in immunocompromised hosts. This is due to the inability of the host immunity to respond appropriately to Aspergillus. An established risk factor for IA is neutropenia that is encountered by patients undergoing chemotherapy. Herein, we investigate the role of neutrophils in modulating host response to Aspergillus. We found that neutrophils had the propensity to suppress proinflammatory cytokine production but through different mechanisms for specific cytokines. Cellular contact was requisite for the modulation of interleukin-1 beta production by Aspergillus with the involvement of complement receptor 3. On the other hand, inhibition of tumour necrosis factor-alpha production (TNF-α) was cell contact-independent and mediated by secreted myeloperoxidase. Specifically, the inhibition of TNF-α by myeloperoxidase was through the TLR4 pathway and involved interference with the mRNA transcription of TNF receptor-associated factor 6/interferon regulatory factor 5. Our study illustrates the extended immune modulatory role of neutrophils beyond its primary phagocytic function. The absence of neutrophils and loss of its inhibitory effect on cytokine production explains the hypercytokinemia seen in neutropenic patients when infected with Aspergillus. © 2017 John Wiley & Sons Ltd.

Interferon alpha inhibits viral replication of a live-attenuated porcine reproductive and respiratory syndrome virus vaccine preventing development of an adaptive immune response in swine

USDA-ARS?s Scientific Manuscript database

Type I interferons, such as interferon alpha (IFNa), contribute to innate antiviral immunity by promoting production of antiviral mediators and are also involved in promoting an adaptive immune response. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating and c...

Community Pharmacists' Perceptions about Pharmaceutical Care of Traditional Medicine Products: A Questionnaire-Based Cross-Sectional Study in Guangzhou, China

PubMed Central

Chen, Xi; Ung, Carolina Oi Lam; Hu, Hao; Liu, Xiaodan; Zhao, Jing; Hu, Yuanjia; Li, Peng; Yang, Qing

2016-01-01

This study aimed to investigate community pharmacists' perceived responsibility, practice behaviors, knowledge, perceived barriers, and improvement measures towards provision of pharmaceutical care in relation to traditional medicine (TM) products in Guangzhou, China. A self-completion questionnaire was used to survey licensed pharmacists working at community pharmacies. This study found that the community pharmacists in Guangzhou, China, were involved in the provision of TM products during their daily practice but only provided pharmaceutical care in this area with a passive attitude. Extrinsic barriers such as lack of scientific evidence for the safety and efficacy of TM products and unclear definition of their roles and responsibilities were highlighted while intrinsic factors such as insufficient TM knowledge were identified. PMID:27066101

The Role of Sustained Attention in the Production of Conjoined Noun Phrases: An Individual Differences Study

PubMed Central

Jongman, Suzanne R.; Meyer, Antje S.; Roelofs, Ardi

2015-01-01

It has previously been shown that language production, performed simultaneously with a nonlinguistic task, involves sustained attention. Sustained attention concerns the ability to maintain alertness over time. Here, we aimed to replicate the previous finding by showing that individuals call upon sustained attention when they plan single noun phrases (e.g., "the carrot") and perform a manual arrow categorization task. In addition, we investigated whether speakers also recruit sustained attention when they produce conjoined noun phrases (e.g., "the carrot and the bucket") describing two pictures, that is, when both the first and second task are linguistic. We found that sustained attention correlated with the proportion of abnormally slow phrase-production responses. Individuals with poor sustained attention displayed a greater number of very slow responses than individuals with better sustained attention. Importantly, this relationship was obtained both for the production of single phrases while performing a nonlinguistic manual task, and the production of noun phrase conjunctions in referring to two spatially separated objects. Inhibition and updating abilities were also measured. These scores did not correlate with our measure of sustained attention, suggesting that sustained attention and executive control are distinct. Overall, the results suggest that planning conjoined noun phrases involves sustained attention, and that language production happens less automatically than has often been assumed. PMID:26335441

Osmoadaptation of wine yeast (Saccharomyces cerevisiae) during Icewine fermentation leads to high levels of acetic acid.

PubMed

Heit, C; Martin, S J; Yang, F; Inglis, D L

2018-06-01

Volatile acidity (VA) production along with gene expression patterns, encoding enzymes involved in both acetic acid production and utilization, were investigated to relate gene expression patterns to the production of undesired VA during Icewine fermentation. Icewine juice and diluted Icewine juice were fermented using the Saccharomyces cerevisiae wine yeast K1-V1116. Acetic acid production increased sixfold during the Icewine fermentation vs the diluted juice condition, while ethyl acetate production increased 2·4-fold in the diluted fermentation relative to the Icewine. Microarray analysis profiled the transcriptional response of K1-V1116 under both conditions. ACS1 and ACS2 were downregulated 19·0-fold and 11·2-fold, respectively, in cells fermenting Icewine juice compared to diluted juice. ALD3 expression was upregulated 14·6-fold, and gene expressions involved in lipid and ergosterol synthesis decreased during Icewine fermentation. Decreased expression of ACS1 and ACS2 together with increased ALD3 expression contributes to the higher acetic acid and lower ethyl acetate levels generated by K1-V1116 fermenting under hyperosmotic stress. This work represents a more comprehensive understanding of how and why commercial wine yeast respond at the transcriptional and metabolic level during fermentation of Icewine juice, and how these responses contribute to increased acetic acid and decreased ethyl acetate production. © 2018 The Society for Applied Microbiology.

Autophagy and self-defense.

PubMed

Martínez-Borra, Jesús; López-Larrea, Carlos

2012-01-01

Autophagy is a highly conserved mechanism which is essential for the maintenance of cellular homeostasis in response to cellular stress. Autophagy has been conserved from yeast to humans as a quality control process that is involved in the recognition and turnover of damaged proteins and organelles. It is also a response mechanism to nutrient starvation. In mammals, autophagy is involved in antigen presentation, tolerance, inflammation and protection against neurodegenerative diseases. The decrease of autophagy during aging reduces the removal of damaged organelles and increases the accumulation of waste products in the cells. In this chapter, we review these aspects of autophagy along with their role in self-nonself distinction, their implication in innate and adaptive immune response, and its dysregulation in the pathology of certain inflammatory and autoimmune diseases.

Chemokine CXCL11 links microbial stimuli to intestinal inflammation

PubMed Central

Liu, Z; Chen, X; Wang, X; Chen, X; Song, C-H; Du, Y; Su, J; Yaseen, S A; Yang, P-C

2011-01-01

Interleukin (IL)-17 plays an important role in the pathogenesis in a number of immune inflammatory disorders. This study aims to investigate the mechanism by which microbial product flagellin is involved in the development of T helper type (Th)17 cells. Serum levels of IL-17 and CXCL9-11 in patients with ulcerative colitis (UC) were evaluated. The source and mechanism of CXC11 release in intestinal mucosa were examined with colonic biopsies from UC patients and a colitis mouse model. The role of flagellin in the development of Th17 cells was studied with a cell co-culture system. High serum levels of CXCL11 and IL-17 were observed in UC. Flagellin could induce the production of CXCL11 in CD14+ cells that facilitated the development of Th17 cells. In a skewed Th1 response environment flagellin induces intestinal inflammation, with IL-17 expression predominant. CXCR3/CXCL11 pathway is involved in microbial product flagellin-induced intestinal inflammation in which the Th17 response plays an important role. PMID:21438871

Interactome analysis of longitudinal pharyngeal infection of cynomolgus macaques by group A Streptococcus.

PubMed

Shea, Patrick R; Virtaneva, Kimmo; Kupko, John J; Porcella, Stephen F; Barry, William T; Wright, Fred A; Kobayashi, Scott D; Carmody, Aaron; Ireland, Robin M; Sturdevant, Daniel E; Ricklefs, Stacy M; Babar, Imran; Johnson, Claire A; Graham, Morag R; Gardner, Donald J; Bailey, John R; Parnell, Michael J; Deleo, Frank R; Musser, James M

2010-03-09

Relatively little is understood about the dynamics of global host-pathogen transcriptome changes that occur during bacterial infection of mucosal surfaces. To test the hypothesis that group A Streptococcus (GAS) infection of the oropharynx provokes a distinct host transcriptome response, we performed genome-wide transcriptome analysis using a nonhuman primate model of experimental pharyngitis. We also identified host and pathogen biological processes and individual host and pathogen gene pairs with correlated patterns of expression, suggesting interaction. For this study, 509 host genes and seven biological pathways were differentially expressed throughout the entire 32-day infection cycle. GAS infection produced an initial widespread significant decrease in expression of many host genes, including those involved in cytokine production, vesicle formation, metabolism, and signal transduction. This repression lasted until day 4, at which time a large increase in expression of host genes was observed, including those involved in protein translation, antigen presentation, and GTP-mediated signaling. The interactome analysis identified 73 host and pathogen gene pairs with correlated expression levels. We discovered significant correlations between transcripts of GAS genes involved in hyaluronic capsule production and host endocytic vesicle formation, GAS GTPases and host fibrinolytic genes, and GAS response to interaction with neutrophils. We also identified a strong signal, suggesting interaction between host gammadelta T cells and genes in the GAS mevalonic acid synthesis pathway responsible for production of isopentenyl-pyrophosphate, a short-chain phospholipid that stimulates these T cells. Taken together, our results are unique in providing a comprehensive understanding of the host-pathogen interactome during mucosal infection by a bacterial pathogen.

Immunotherapy in the management of sepsis.

PubMed Central

Fagan, E. A.; Singer, M.

1995-01-01

The pathophysiological effects of severe sepsis, septic shock and related syndromes result from tissues damaged by the uncontrolled production of the mediators of inflammation. Early deaths are related primarily to the acute effects of the systemic inflammatory response. Later deaths are related more closely to the consequences of multiple organ dysfunction. Monoclonal antibodies and other immunotherapies have been developed against bacterial products, cytokines and other mediators involved in this systemic inflammatory response. Immunotherapies may improve outcome in the critically ill with sepsis if used early and as part of the therapeutic regimen of antimicrobial agents and intensive care support. PMID:7724438

Neutrophil elastase enhances IL-12p40 production by lipopolysaccharide-stimulated macrophages via transactivation of the PAR-2/EGFR/TLR4 signaling pathway.

PubMed

Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo

2016-07-01

Proteinase-activated receptor 2 (PAR-2) and toll-like receptor 4 (TLR4) are involved in innate immune responses and signaling cross-talk between these receptor molecules has the potential to augment an ongoing inflammatory response. The aim of this study was to evaluate the possible cooperative influence of PAR-2 and TLR4 on IL-12p40 production by macrophages after stimulation with lipopolysaccharide (LPS). During culture, GM-CSF upregulated PAR-2 expression by macrophages in a time-dependent manner. Stimulation with LPS enhanced IL-12p40 production by macrophages in a concentration-dependent manner. While human neutrophil elastase (HNE) did not induce IL-12p40 production, pretreatment of macrophages with HNE synergistically increased the IL-12p40 protein level after LPS exposure. Silencing of TLR4 with small interfering RNA blunted the synergistic enhancement of IL-12p40 by HNE combined with LPS. Silencing of β-arrestin 2, p22phox, or ERK1/2 also inhibited an increase of IL-12p40. Interestingly, transfection of macrophages with small interfering RNA duplexes for DUOX-2, EGFR, TLR4, or TRAF6 significantly blunted the increase of IL-12p40 in response to treatment with HNE plus LPS. U73122 and Rottlerin also inhibited the increased production of IL-12p40. In conclusion, HNE is involved in transactivation of TLR4 through activation of DUOX-2/EGFR and synergistically enhances IL-12p40 production by macrophages stimulated with LPS. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficient sparse matrix-matrix multiplication for computing periodic responses by shooting method on Intel Xeon Phi

NASA Astrophysics Data System (ADS)

Stoykov, S.; Atanassov, E.; Margenov, S.

2016-10-01

Many of the scientific applications involve sparse or dense matrix operations, such as solving linear systems, matrix-matrix products, eigensolvers, etc. In what concerns structural nonlinear dynamics, the computations of periodic responses and the determination of stability of the solution are of primary interest. Shooting method iswidely used for obtaining periodic responses of nonlinear systems. The method involves simultaneously operations with sparse and dense matrices. One of the computationally expensive operations in the method is multiplication of sparse by dense matrices. In the current work, a new algorithm for sparse matrix by dense matrix products is presented. The algorithm takes into account the structure of the sparse matrix, which is obtained by space discretization of the nonlinear Mindlin's plate equation of motion by the finite element method. The algorithm is developed to use the vector engine of Intel Xeon Phi coprocessors. It is compared with the standard sparse matrix by dense matrix algorithm and the one developed by Intel MKL and it is shown that by considering the properties of the sparse matrix better algorithms can be developed.

Involvement of 2-C-methyl-D-erythritol-4-phosphate pathway in biosynthesis of aphidicolin-like tetracyclic diterpene of Scoparia dulcis.

PubMed

Nkembo, Marguerite Kasidimoko; Lee, Jung-Bum; Nakagiri, Takeshi; Hayashi, Toshimitsu

2006-05-01

Specific inhibitors of the MVA pathway (pravastatin) and the MEP pathway (fosmidomycin) were used to interfere with the biosynthetic flux which leads to the production of aphidicolin-like diterpene in leaf organ cultures of Scoparia dulcis. Treatment of leaf organs with fosmidomycin resulted in dose dependent inhibition of chlorophylls, carotenoids, scopadulcic acid B (SDB) and phytol production, and no effect on sterol production was observed. In response to the pravastatin treatment, a significant decrease in sterol and perturbation of SDB production was observed.

The RNA chaperone, Hfq, controls two luxR-type regulators and plays a key role in pathogenesis and production of antibiotics in Serratia sp. ATCC 39006.

PubMed

Wilf, Nabil M; Williamson, Neil R; Ramsay, Joshua P; Poulter, Simon; Bandyra, Kasia J; Salmond, George P C

2011-10-01

Serratia sp. ATCC 39006 (S39006) is a Gram-negative bacterium that is virulent in plant (potato) and animal (Caenorhabditis elegans) models. It produces two secondary metabolite antibiotics, a prodigiosin and a carbapenem, and the exoenzymes, pectate lyase and cellulase. A complex regulatory network that includes quorum sensing (QS) controls production of prodigiosin. While many aspects of the regulation of the metabolites and exoenzymes are well understood, the potential role in this network of the RNA chaperone Hfq and dependent small regulatory RNAs has not been characterized. Hfq is an RNA chaperone involved in post-transcriptional regulation that plays a key role in stress response and virulence in diverse bacterial species. To explore whether Hfq-dependent processes might contribute to the regulation of antibiotic production we constructed an S39006 Δhfq mutant. Production of prodigiosin and carbapenem was abolished in this mutant strain, while production of the QS signalling molecule, butanoyl homoserine lactone (BHL), was unaffected. Using transcriptional fusions, we found that Hfq regulates the QS response regulators, SmaR and CarR. Additionally, exoenzyme production and swimming motility were decreased in a Δhfq mutant, and virulence was attenuated in potato and C. elegans models. These results suggest that an Hfq-dependent pathway is involved in the regulation of virulence and secondary metabolite production in S39006. © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.

Platelet Glycoprotein lb-1X and Malignancy

DTIC Science & Technology

2011-09-01

Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proc Natl Acad Sci...JM, Hakim J, de Prost D. Vascular endothelial growth factor production by fibroblasts in response to factor VIIa binding to tissue factor involves...interactions in vitro. (14) The extrinsic pathway of coagulation triggered by factor VII ( FVII ) and tissue factor can be activated in cancer patients. (15

Liability for Personal Injury Caused by Defective Medical Computer Programs

PubMed Central

Brannigan, Vincent M.

1980-01-01

Defective medical computer programs can cause personal injury. Financial responsibility for the injury under tort law will turn on several factors: whether the program is a product or a service, what types of defect exist in the product, and who produced the program. The factors involved in making these decisions are complex, but knowledge of the relevant issues can assist computer personnel in avoiding liability.

Surface enlargement factor of rumen papillae and expression of genes involved in dermatological diseases and their relationships with feed intake in beef steers

USDA-ARS?s Scientific Manuscript database

Feed costs make up the largest portion of the total cost to produce beef. One way to reduce this cost, thereby increasing profitability of beef production, is to improve feed efficiency. The rumen is responsible for digestion and absorption of nutrients and microbial by-products and may play a sig...

The Market Responses to the Government Regulation of Chlorinated Solvents: A Policy Analysis

DTIC Science & Technology

1988-10-01

in the process of statistical estimation of model parameters. The results of the estimation process applied to chlorinated solvent markets show the...93 C.5. Marginal Feedstock Cost Series Estimates for Process Share of Total Production .................................. 94 F.I...poliay context for this research. Section III provides analysis necessary to understand the chemicals involved, their production processes and costs, and

Prevalence and determinants of direct and generative modes of production of episodic future thoughts in the word cueing paradigm.

PubMed

Jeunehomme, Olivier; D'Argembeau, Arnaud

2016-01-01

Recent research suggests that episodic future thoughts can be formed through the same dual mechanisms, direct and generative, as autobiographical memories. However, the prevalence and determinants of the direct production of future event representations remain unclear. Here, we addressed this issue by collecting self-reports of production modes, response times (RTs), and verbal protocols for the production past and future events in the word cueing paradigm. Across three experiments, we found that both past and future events were frequently reported to come directly to mind in response to the cue, and RTs confirmed that events were produced faster for direct than for generative responses. When looking at the determinants of direct responses, we found that most past and future events that were directly produced had already been thought of on a previous occasion, and the frequency of previous thoughts predicted the occurrence of direct access. The direct production of autobiographical thoughts was also more frequent for past and future events that were judged important and emotionally intense. Collectively, these findings provide novel evidence that the direct production of episodic future thoughts is frequent in the word cueing paradigm and often involves the activation of personally significant "memories of the future."

Enterobacter gergoviae membrane modifications are involved in the adaptive response to preservatives used in cosmetic industry.

PubMed

Périamé, Marina; Pagès, Jean-Marie; Davin-Regli, Anne

2015-01-01

The objective of this study was to understand the adaptive mechanisms in Enterobacter gergoviae which are involved in recurrent contaminations in cosmetic products that are incorporated with preservatives. Bacterial strains from two backgrounds were examined for a profound understanding of the mechanisms of adaptation against preservatives. It included a series of Ent. gergoviae strain-ATCC 33028 derivatives, isolated using increasing methylisothiazolinone-chloromethylisothiazolinone (MIT-CMIT) and triclosan concentrations. The other series was of Ent. gergoviae isolates from cosmetic products exhibiting MIT-CMIT and triclosan resistance. We evaluated the outer membrane protein modifications and efflux mechanisms activities responsible for the resistant trait via immunoblotting assays. Additionally, for understanding the efflux activity real-time efflux, experiments were performed. A cross-insusceptibility between preservatives and some disinfectants was observed in MIT-CMIT-resistant derivative isolates, but antibiotics susceptibility was not altered. Resistance to EDTA was significant in all preservatives insusceptible derivative strains, indicating modifications in the LPS layer. Furthermore, an array of real-time efflux assays indicated different activity levels while no variations were detected in porins and AcrAB-TolC pumps production. Overexpression of a specific flagellin-type protein was observed in one of the MIT-CMIT- and triclosan-resistant strains. Another candidate, a 25-kDa peroxiredoxin enzyme involved in oxidative detoxification, was identified to be overexpressed in MIT-CMIT derivative. A similar profile was also observed among strains isolated from cosmetic products. Our study highlights the existence of adaptive mechanisms such as overexpression of detoxifying enzymes, flagellin, modification of membrane structure/function in Ent. gergoviae. They might be involved in recurrent episodes of contaminations occurring in the cosmetic production lines. No cross-resistance could be observed with antibiotics when MICs to preservatives were increased; however, a decrease in the disinfectants bactericidal effects was confirmed in preservative-tolerant strains. This will impact industry disinfection strategies treatment against bacteria. © 2014 The Society for Applied Microbiology.

Mechanical stress regulation of plant growth and development

NASA Technical Reports Server (NTRS)

Mitchell, C. A.; Myers, P. N.

1995-01-01

The authors introduce the chapter with a discussion of lessons from nature, agriculture, and landscapes; terms and definitions; and an historical perspective of mechanical stress regulation of plant growth and development. Topics include developmental responses to mechanical stress; mechanical stress-environment interactions; metabolic, productivity, and compositional changes; hormonal involvement; mechanoperception and early transduction mechanisms; applications in agriculture; and research implications. The discussion of hormonal involvement in mechanical stress physiology includes ethylene, auxin, gibberellins, and other phytohormones. The discussion of applications in agriculture examines windbreaks, nursery practices, height control and conditioning, and enhancement of growth and productivity. Implications for research are related to handling plant materials, space biology, and future research needs.

Consumer product safety: A systems problem

NASA Technical Reports Server (NTRS)

Clark, C. C.

1971-01-01

The manufacturer, tester, retailer, consumer, repairer disposer, trade and professional associations, national and international standards bodies, and governments in several roles are all involved in consumer product safety. A preliminary analysis, drawing on system safety techniques, is utilized to distinguish the inter-relations of these many groups and the responsibilities that they are or could take for product safety, including the slow accident hazards as well as the more commonly discussed fast accident hazards. The importance of interactive computer aided information flow among these groups is particularly stressed.

Reconstruction and visualization of carbohydrate, N-glycosylation pathways in Pichia pastoris CBS7435 using computational and system biology approaches.

PubMed

Srivastava, Akriti; Somvanshi, Pallavi; Mishra, Bhartendu Nath

2013-06-01

Pichia pastoris is an efficient expression system for production of recombinant proteins. To understand its physiology for building novel applications it is important to understand and reconstruct its metabolic network. The metabolic reconstruction approach connects genotype with phenotype. Here, we have attempted to reconstruct carbohydrate metabolism pathways responsible for high biomass density and N-glycosylation pathways involved in the post translational modification of proteins of P. pastoris CBS7435. Both these metabolic pathways play a crucial role in heterologous protein production. We report novel, missing and unannotated enzymes involved in the target metabolic pathways. A strong possibility of cellulose and xylose metabolic processes in P. pastoris CBS7435 suggests its use in the area of biofuels. The reconstructed metabolic networks can be used for increased yields and improved product quality, for designing appropriate growth medium, for production of recombinant therapeutics and for making biofuels.

Guaranteeing a captive audience: coordinated regulation of gene transfer agent (GTA) production and recipient capability by cellular regulators.

PubMed

Westbye, Alexander B; Beatty, J Thomas; Lang, Andrew S

2017-08-01

Gene transfer agents (GTAs) are bacteriophage-like particles produced by many prokaryotes. Several members of the Alphaproteobacteria produce a class of genetically-related GTAs that is best studied in Rhodobacter capsulatus. DNA transfer by the R. capsulatus GTA (RcGTA) combines aspects of both transduction and natural transformation, as recipient cells require a natural transformation-like system to incorporate donated DNA. The genes involved in RcGTA production and recipient capability are located at multiple loci in the bacterial genome; however, a conserved phosphorelay containing the response regulator CtrA and a quorum sensing system regulate both RcGTA production and recipient capability. This review highlights recent discoveries in RcGTA biology, and focuses on the co-regulation of genes involved in RcGTA production and recipient capability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gammadelta T lymphocytes from cystic fibrosis patients and healthy donors are high TNF-alpha and IFN-gamma-producers in response to Pseudomonas aeruginosa.

PubMed

Raga, Salvador; Julià, M Rosa; Crespí, Catalina; Figuerola, Joan; Martínez, Natalia; Milà, Joan; Matamoros, Núria

2003-01-01

Gammadelta T cells have an important immunoregulatory and effector function through cytokine release. They are involved in the responses to Gram-negative bacterium and in protection of lung epithelium integrity. On the other hand, they have been implicated in airway inflammation. The aim of the present work was to study intracytoplasmic IL-2, IL-4, IFN-gamma and TNF-alpha production by gammadelta and alphabeta T lymphocytes from cystic fibrosis patients and healthy donors in response to Pseudomonas aeruginosa (PA). Flow cytometric detection was performed after peripheral blood mononuclear cells (PBMC) culture with a cytosolic extract from PA and restimulation with phorbol ester plus ionomycine. Proliferative responses, activation markers and receptor usage of gammadelta T cells were also evaluated. The highest production of cytokine was of TNF-alpha and IFN-gamma, gammadelta being better producers than alphabeta. No differences were found between patients and controls. The Vgamma9delta2 subset of gammadelta T cells was preferentially expanded. CD25 and CD45RO expression by the alphabeta T subset and PBMC proliferative response to PA were defective in cystic fibrosis lymphocytes. Our results support the hypothesis that gammadelta T lymphocytes play an important role in the immune response to PA and in the chronic inflammatory lung reaction in cystic fibrosis patients. They do not confirm the involvement of a supressed Th1 cytokine response in the pathogenesis of this disease.

Immune mechanisms in fish skin against monogeneans--a model.

PubMed

Buchmann, K

1999-01-01

Host responses against skin inhabiting monogeneans are commonly observed but the responsible immune mechanisms in the fish skin are sufficiently described. Based on recent knowledge of fish immunity and skin response mechanisms in mammals a model for the skin immunity in fish to monogenean infections is proposed. Important cellular components of the model are the epithelial cells, the mucous cells and leucocytes. The release of cytokines, e.g., IL-1, following mechanical or chemical injury of the epithelial cells, initiates a series of events leading to decrease of the ectoparasite population. Cytokines (e.g., IL-1, TNF, INF) are suggested to affect secretions from mucous cell and attract neutrophils and macrophages. Leukotrienes are probably involved in the inflammatory reactions. The subsequent production of humoral substances (among others complement factors and peptides) could be responsible for the antiparasitic response in the later stages of infection. Although non-specific factors dominate the response, the involvement of specific antibodies and lymphocytes cannot be excluded.

Hyperpolarisation of cultured human chondrocytes following cyclical pressure-induced strain: evidence of a role for alpha 5 beta 1 integrin as a chondrocyte mechanoreceptor.

PubMed

Wright, M O; Nishida, K; Bavington, C; Godolphin, J L; Dunne, E; Walmsley, S; Jobanputra, P; Nuki, G; Salter, D M

1997-09-01

Mechanical stimuli influence chondrocyte metabolism, inducing changes in intracellular cyclic adenosine monophosphate and proteoglycan production. We have previously demonstrated that primary monolayer cultures of human chondrocytes have an electrophysiological response after intermittent pressure-induced strain characterised by a membrane hyperpolarisation of approximately 40%. The mechanisms responsible for these changes are not fully understood but potentially involve signalling molecules such as integrins that link extracellular matrix with cytoplasmic components. The results reported in this paper demonstrate that the transduction pathways involved in the hyperpolarisation response of human articular chondrocytes in vitro after cyclical pressure-induced strain involve alpha 5 beta 1 integrin. We have demonstrated, using pharmacological inhibitors of a variety of intracellular signalling pathways, that the actin cytoskeleton, the phospholipase C calmodulin pathway, and both tyrosine protein kinase and protein kinase C activities are important in the transduction of the electrophysiological response. These results suggest that alpha 5 beta 1 is an important chondrocyte mechanoreceptor and a potential regulator of chondrocyte function.

Reactive Oxygen Species Function to Mediate the Fe Deficiency Response in an Fe-Efficient Apple Genotype: An Early Response Mechanism for Enhancing Reactive Oxygen Production.

PubMed

Sun, Chaohua; Wu, Ting; Zhai, Longmei; Li, Duyue; Zhang, Xinzhong; Xu, Xuefeng; Ma, Huiqin; Wang, Yi; Han, Zhenhai

2016-01-01

Reactive oxygen species (ROS) are important signaling molecules in plants that contribute to stress acclimation. This study demonstrated that ROS play a critical role in Fe deficiency-induced signaling at an early stage in Malus xiaojinensis . Once ROS production has been initiated, prolonged Fe starvation leads to activation of ROS scavenging mechanisms. Further, we demonstrated that ROS scavengers are involved in maintaining the cellular redox homeostasis during prolonged Fe deficiency treatment. Taken together, our results describe a feedback repression loop for ROS to preserve redox homeostasis and maintain a continuous Fe deficiency response in the Fe-efficient woody plant M. xiaojinensis . More broadly, this study reveals a new mechanism in which ROS mediate both positive and negative regulation of plant responses to Fe deficiency stress.

Metaproteomics and ultrastructure characterization of Komagataeibacter spp. involved in high-acid spirit vinegar production.

PubMed

Andrés-Barrao, Cristina; Saad, Maged M; Cabello Ferrete, Elena; Bravo, Daniel; Chappuis, Marie-Luise; Ortega Pérez, Ruben; Junier, Pilar; Perret, Xavier; Barja, François

2016-05-01

Acetic acid bacteria (AAB) are widespread microorganisms in nature, extensively used in food industry to transform alcohols and sugar alcohols into their corresponding organic acids. Specialized strains are used in the production of vinegar through the oxidative transformation of ethanol into acetic acid. The main AAB involved in the production of high-acid vinegars using the submerged fermentation method belong to the genus Komagataeibacter, characterized by their higher ADH stability and activity, and higher acetic acid resistance (15-20%), compared to other AAB. In this work, the bacteria involved in the production of high-acid spirit vinegar through a spontaneous acetic acid fermentation process was studied. The analysis using a culture-independent approach revealed a homogeneous bacterial population involved in the process, identified as Komagataeibacter spp. Differentially expressed proteins during acetic acid fermentation were investigated by using 2D-DIGE and mass spectrometry. Most of these proteins were functionally related to stress response, the TCA cycle and different metabolic processes. In addition, scanning and transmission electron microscopy and specific staining of polysaccharide SDS-PAGE gels confirmed that Komagataeibacter spp. lacked the characteristic polysaccharide layer surrounding the outer membrane that has been previously reported to have an important role in acetic acid resistance in the genus Acetobacter. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Aroma and perfume allergy: anathema for some epicurean appeal?].

PubMed

Goffin, V; Nikkels, A F; Cornil, F; Deleixhe-Mauhin, F; Piérard-Franchimont, C; Piérard, G E

2002-09-01

Aromas and fragrances are present in many cosmetics, some topical drugs, food and various hygiene, household and industrial products. They can be responsible for contact dermatitis. Multiple sensitizations can even involve in various combinations some fragrance compounds, a given degradation product or a contaminant. The diagnosis relies on clinical examination and oriented anamnesis. A histological examination is sometimes necessary. Specific path testing brings insight on the culprit chemical compounds.

Genome-Wide Transcriptome Analyses of Silicon Metabolism in Phaeodactylum tricornutum Reveal the Multilevel Regulation of Silicic Acid Transporters

PubMed Central

Sapriel, Guillaume; Quinet, Michelle; Heijde, Marc; Jourdren, Laurent; Tanty, Véronique; Luo, Guangzuo; Le Crom, Stéphane; Lopez, Pascal Jean

2009-01-01

Background Diatoms are largely responsible for production of biogenic silica in the global ocean. However, in surface seawater, Si(OH)4 can be a major limiting factor for diatom productivity. Analyzing at the global scale the genes networks involved in Si transport and metabolism is critical in order to elucidate Si biomineralization, and to understand diatoms contribution to biogeochemical cycles. Methodology/Principal Findings Using whole genome expression analyses we evaluated the transcriptional response to Si availability for the model species Phaeodactylum tricornutum. Among the differentially regulated genes we found genes involved in glutamine-nitrogen pathways, encoding putative extracellular matrix components, or involved in iron regulation. Some of these compounds may be good candidates for intracellular intermediates involved in silicic acid storage and/or intracellular transport, which are very important processes that remain mysterious in diatoms. Expression analyses and localization studies gave the first picture of the spatial distribution of a silicic acid transporter in a diatom model species, and support the existence of transcriptional and post-transcriptional regulations. Conclusions/Significance Our global analyses revealed that about one fourth of the differentially expressed genes are organized in clusters, underlying a possible evolution of P. tricornutum genome, and perhaps other pennate diatoms, toward a better optimization of its response to variable environmental stimuli. High fitness and adaptation of diatoms to various Si levels in marine environments might arise in part by global regulations from gene (expression level) to genomic (organization in clusters, dosage compensation by gene duplication), and by post-transcriptional regulation and spatial distribution of SIT proteins. PMID:19829693

48 CFR 253.209-1 - Responsible prospective contractors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... required service. (B) Production capability. An evaluation of the prospective contractor's ability to plan.... (C) Quality assurance capability. An assessment of the prospective contractor's capability to meet the quality assurance requirements of the proposed contract. It may involve an evaluation of the...

40 CFR 35.6230 - Application requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Response Actions Core Program Cooperative Agreements § 35.6230 Application requirements. To receive a Core... number of products to be completed, and a schedule for implementation. Eligible activities under Core... to sustain and increase recipient involvement in CERCLA implementation, and the impact of Core...

40 CFR 35.6230 - Application requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Response Actions Core Program Cooperative Agreements § 35.6230 Application requirements. To receive a Core... number of products to be completed, and a schedule for implementation. Eligible activities under Core... to sustain and increase recipient involvement in CERCLA implementation, and the impact of Core...

Serotonin depletion can enhance the cerebrovascular responses induced by cortical spreading depression via the nitric oxide pathway.

PubMed

Saengjaroentham, Chonlawan; Supornsilpchai, Weera; Ji-Au, Wilawan; Srikiatkhachorn, Anan; Maneesri-le Grand, Supang

2015-02-01

Serotonin (5-HT) is an important neurotransmitter involved in the control of neural and vascular responses. 5-HT depletion can induce several neurological disorders, including migraines. Studies on a cortical spreading depression (CSD) migraine animal model showed that the cortical neurons sensitivity, vascular responses, and nitric oxide (NO) production were significantly increased in 5-HT depletion. However, the involvement of NO in the cerebrovascular responses in 5-HT depletion remains unclear. This study aimed to investigate the role of NO in the CSD-induced alterations of cerebral microvessels in 5-HT depletion. Rats were divided into four groups: control, control with L-NAME treatment, 5-HT depleted, and 5-HT depleted with L-NAME treatment. 5-HT depletion was induced by intraperitoneal injection with para-chlorophenylalanine (PCPA) 3 days before the experiment. The CSD was triggered by KCl application. After the second wave of CSD, N-nitro-l-arginine methyl ester (L-NAME) or saline was intravenously injected into the rats with or without L-NAME treatment groups, respectively. The intercellular adhesion molecules-1 (ICAM-1), cell adhesion molecules-1 (VCAM-1), and the ultrastructural changes of the cerebral microvessels were examined. The results showed that 5-HT depletion significantly increased ICAM-1 and VCAM-1 expressions in the cerebral cortex. The number of endothelial pinocytic vesicles and microvilli was higher in the 5-HT depleted group when compared to the control. Interestingly, L-NAME treatment significantly reduced the abnormalities observed in the 5-HT depleted group. The results of this study demonstrated that an increase of NO production is one of the mechanisms involved in the CSD-induced alterations of the cerebrovascular responses in 5-HT depletion.

Understanding The Neural Mechanisms Involved In Sensory Control Of Voice Production

PubMed Central

Parkinson, Amy L.; Flagmeier, Sabina G.; Manes, Jordan L.; Larson, Charles R.; Rogers, Bill; Robin, Donald A.

2012-01-01

Auditory feedback is important for the control of voice fundamental frequency (F0). In the present study we used neuroimaging to identify regions of the brain responsible for sensory control of the voice. We used a pitch-shift paradigm where subjects respond to an alteration, or shift, of voice pitch auditory feedback with a reflexive change in F0. To determine the neural substrates involved in these audio-vocal responses, subjects underwent fMRI scanning while vocalizing with or without pitch-shifted feedback. The comparison of shifted and unshifted vocalization revealed activation bilaterally in the superior temporal gyrus (STG) in response to the pitch shifted feedback. We hypothesize that the STG activity is related to error detection by auditory error cells located in the superior temporal cortex and efference copy mechanisms whereby this region is responsible for the coding of a mismatch between actual and predicted voice F0. PMID:22406500

Transcriptome analysis of Lactococcus lactis subsp. lactis during milk acidification as affected by dissolved oxygen and the redox potential.

PubMed

Larsen, Nadja; Moslehi-Jenabian, Saloomeh; Werner, Birgit Brøsted; Jensen, Maiken Lund; Garrigues, Christel; Vogensen, Finn Kvist; Jespersen, Lene

2016-06-02

Performance of Lactococcus lactis as a starter culture in dairy fermentations depends on the levels of dissolved oxygen and the redox state of milk. In this study the microarray analysis was used to investigate the global gene expression of L. lactis subsp. lactis DSM20481(T) during milk acidification as affected by oxygen depletion and the decrease of redox potential. Fermentations were carried out at different initial levels of dissolved oxygen (dO2) obtained by milk sparging with oxygen (high dO2, 63%) or nitrogen (low dO2, 6%). Bacterial exposure to high initial oxygen resulted in overexpression of genes involved in detoxification of reactive oxygen species (ROS), oxidation-reduction processes, biosynthesis of trehalose and down-regulation of genes involved in purine nucleotide biosynthesis, indicating that several factors, among them trehalose and GTP, were implicated in bacterial adaptation to oxidative stress. Generally, transcriptional changes were more pronounced during fermentation of oxygen sparged milk. Genes up-regulated in response to oxygen depletion were implicated in biosynthesis and transport of pyrimidine nucleotides, branched chain amino acids and in arginine catabolic pathways; whereas genes involved in salvage of nucleotides and cysteine pathways were repressed. Expression pattern of genes involved in pyruvate metabolism indicated shifts towards mixed acid fermentation after oxygen depletion with production of specific end-products, depending on milk treatment. Differential expression of genes, involved in amino acid and pyruvate pathways, suggested that initial oxygen might influence the release of flavor compounds and, thereby, flavor development in dairy fermentations. The knowledge of molecular responses involved in adaptation of L. lactis to the shifts of redox state and pH during milk fermentations is important for the dairy industry to ensure better control of cheese production. Copyright © 2016 Elsevier B.V. All rights reserved.

Vocal parameters that indicate threat level correlate with FOS immunolabeling in social and vocal control brain regions.

PubMed

Ellis, Jesse M S; Riters, Lauren V

2012-01-01

Transmitting information via communicative signals is integral to interacting with conspecifics, and some species achieve this task by varying vocalizations to reflect context. Although signal variation is critical to social interactions, the underlying neural control has not been studied. In response to a predator, black-capped chickadees (Poecile atricapilla) produce mobbing calls (chick-a-dee calls) with various parameters, some of which convey information about the threat stimulus. We predicted that vocal parameters indicative of threat would be associated with distinct patterns of neuronal activity within brain areas involved in social behavior and those involved in the sensorimotor control of vocal production. To test this prediction, we measured the syntax and structural aspects of chick-a-dee call production in response to a hawk model and assessed the protein product of the immediate early gene FOS in brain regions implicated in context-specific vocal and social behavior. These regions include the medial preoptic area (POM) and lateral septum (LS), as well as regions involved in vocal motor control, including the dorsomedial nucleus of the intercollicular complex and the HVC. We found correlations linking call rate (previously demonstrated to reflect threat) to labeling in the POM and LS. Labeling in the HVC correlated with the number of D notes per call, which may also signal threat level. Labeling in the call control region dorsomedial nucleus was associated with the structure of D notes and the overall number of notes, but not call rate or type of notes produced. These results suggest that the POM and LS may influence attributes of vocalizations produced in response to predators and that the brain region implicated in song control, the HVC, also influences call production. Because variation in chick-a-dee call rate indicates predator threat, we speculate that these areas could integrate with motor control regions to imbue mobbing signals with additional information about threat level. Copyright © 2011 S. Karger AG, Basel.

Role of microRNAs involved in plant response to nitrogen and phosphorous limiting conditions

PubMed Central

Nguyen, Giao N.; Rothstein, Steven J.; Spangenberg, German; Kant, Surya

2015-01-01

Plant microRNAs (miRNAs) are a class of small non-coding RNAs which target and regulate the expression of genes involved in several growth, development, and metabolism processes. Recent researches have shown involvement of miRNAs in the regulation of uptake and utilization of nitrogen (N) and phosphorus (P) and more importantly for plant adaptation to N and P limitation conditions by modifications in plant growth, phenology, and architecture and production of secondary metabolites. Developing strategies that allow for the higher efficiency of using both N and P fertilizers in crop production is important for economic and environmental benefits. Improved crop varieties with better adaptation to N and P limiting conditions could be a key approach to achieve this effectively. Furthermore, understanding on the interactions between N and P uptake and use and their regulation is important for the maintenance of nutrient homeostasis in plants. This review describes the possible functions of different miRNAs and their cross-talk relevant to the plant adaptive responses to N and P limiting conditions. In addition, a comprehensive understanding of these processes at molecular level and importance of biological adaptation for improved N and P use efficiency is discussed. PMID:26322069

Role of microRNAs involved in plant response to nitrogen and phosphorous limiting conditions.

PubMed

Nguyen, Giao N; Rothstein, Steven J; Spangenberg, German; Kant, Surya

2015-01-01

Plant microRNAs (miRNAs) are a class of small non-coding RNAs which target and regulate the expression of genes involved in several growth, development, and metabolism processes. Recent researches have shown involvement of miRNAs in the regulation of uptake and utilization of nitrogen (N) and phosphorus (P) and more importantly for plant adaptation to N and P limitation conditions by modifications in plant growth, phenology, and architecture and production of secondary metabolites. Developing strategies that allow for the higher efficiency of using both N and P fertilizers in crop production is important for economic and environmental benefits. Improved crop varieties with better adaptation to N and P limiting conditions could be a key approach to achieve this effectively. Furthermore, understanding on the interactions between N and P uptake and use and their regulation is important for the maintenance of nutrient homeostasis in plants. This review describes the possible functions of different miRNAs and their cross-talk relevant to the plant adaptive responses to N and P limiting conditions. In addition, a comprehensive understanding of these processes at molecular level and importance of biological adaptation for improved N and P use efficiency is discussed.

Differential Timing of Spider Mite-Induced Direct and Indirect Defenses in Tomato Plants1[w

PubMed Central

Kant, Merijn R.; Ament, Kai; Sabelis, Maurice W.; Haring, Michel A.; Schuurink, Robert C.

2004-01-01

Through a combined metabolomics and transcriptomics approach we analyzed the events that took place during the first 5 d of infesting intact tomato (Lycopersicon esculentum) plants with spider mites (Tetranychus urticae). Although the spider mites had caused little visible damage to the leaves after 1 d, they had already induced direct defense responses. For example, proteinase inhibitor activity had doubled and the transcription of genes involved in jasmonate-, salicylate-, and ethylene-regulated defenses had been activated. On day four, proteinase inhibitor activity and particularly transcript levels of salicylate-regulated genes were still maintained. In addition, genes involved in phospholipid metabolism were up-regulated on day one and those in the secondary metabolism on day four. Although transcriptional up-regulation of the enzymes involved in the biosynthesis of monoterpenes and diterpenes already occurred on day one, a significant increase in the emission of volatile terpenoids was delayed until day four. This increase in volatile production coincided with the increased olfactory preference of predatory mites (Phytoseiulus persimilis) for infested plants. Our results indicate that tomato activates its indirect defenses (volatile production) to complement the direct defense response against spider mites. PMID:15122016

JPRS Report, China

DTIC Science & Technology

1991-02-14

payments are due as stipulated in the national debt- for the better in the market slump, and there will still be payment program. The banks are responsible ...pluck up met, as well as the demands on the international market . their courage and confidence in conquering their diffi- The adjustment of the product...ruled that those involved in and which planned prices were primary and market regula- those responsible for adulteration and deception when tion prices

Analysis of the Effects of the Bruton's tyrosine kinase (Btk) Inhibitor Ibrutinib on Monocyte Fcγ Receptor (FcγR) Function*

PubMed Central

Ren, Li; Campbell, Amanda; Fang, Huiqing; Gautam, Shalini; Elavazhagan, Saranya; Fatehchand, Kavin; Mehta, Payal; Stiff, Andrew; Reader, Brenda F.; Mo, Xiaokui; Byrd, John C.; Carson, William E.; Butchar, Jonathan P.; Tridandapani, Susheela

2016-01-01

The irreversible Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has shown efficacy against B-cell tumors such as chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma. Fcγ receptors (FcγR) on immune cells such as macrophages play an important role in tumor-specific antibody-mediated immune responses, but many such responses involve Btk. Here we tested the effects of ibrutinib on FcγR-mediated activities in monocytes. We found that ibrutinib did not affect monocyte FcγR-mediated phagocytosis, even at concentrations higher than those achieved physiologically, but suppressed FcγR-mediated cytokine production. We confirmed these findings in macrophages from Xid mice in which Btk signaling is defective. Because calcium flux is a major event downstream of Btk, we tested whether it was involved in phagocytosis. The results showed that blocking intracellular calcium flux decreased FcγR-mediated cytokine production but not phagocytosis. To verify this, we measured activation of the GTPase Rac, which is responsible for actin polymerization. Results showed that ibrutinib did not inhibit Rac activation, nor did the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester). We next asked whether the effect of ibrutinib on monocyte FcγR-mediated cytokine production could be rescued by IFNγ priming because NK cells produce IFNγ in response to antibody therapy. Pretreatment of monocytes with IFNγ abrogated the effects of ibrutinib on FcγR-mediated cytokine production, suggesting that IFNγ priming could overcome this Btk inhibition. Furthermore, in monocyte-natural killer cell co-cultures, ibrutinib did not inhibit FcγR-mediated cytokine production despite doing so in single cultures. These results suggest that combining ibrutinib with monoclonal antibody therapy could enhance chronic lymphocytic leukemia cell killing without affecting macrophage effector function. PMID:26627823

Analysis of the Effects of the Bruton's tyrosine kinase (Btk) Inhibitor Ibrutinib on Monocyte Fcγ Receptor (FcγR) Function.

PubMed

Ren, Li; Campbell, Amanda; Fang, Huiqing; Gautam, Shalini; Elavazhagan, Saranya; Fatehchand, Kavin; Mehta, Payal; Stiff, Andrew; Reader, Brenda F; Mo, Xiaokui; Byrd, John C; Carson, William E; Butchar, Jonathan P; Tridandapani, Susheela

2016-02-05

The irreversible Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has shown efficacy against B-cell tumors such as chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma. Fcγ receptors (FcγR) on immune cells such as macrophages play an important role in tumor-specific antibody-mediated immune responses, but many such responses involve Btk. Here we tested the effects of ibrutinib on FcγR-mediated activities in monocytes. We found that ibrutinib did not affect monocyte FcγR-mediated phagocytosis, even at concentrations higher than those achieved physiologically, but suppressed FcγR-mediated cytokine production. We confirmed these findings in macrophages from Xid mice in which Btk signaling is defective. Because calcium flux is a major event downstream of Btk, we tested whether it was involved in phagocytosis. The results showed that blocking intracellular calcium flux decreased FcγR-mediated cytokine production but not phagocytosis. To verify this, we measured activation of the GTPase Rac, which is responsible for actin polymerization. Results showed that ibrutinib did not inhibit Rac activation, nor did the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester). We next asked whether the effect of ibrutinib on monocyte FcγR-mediated cytokine production could be rescued by IFNγ priming because NK cells produce IFNγ in response to antibody therapy. Pretreatment of monocytes with IFNγ abrogated the effects of ibrutinib on FcγR-mediated cytokine production, suggesting that IFNγ priming could overcome this Btk inhibition. Furthermore, in monocyte-natural killer cell co-cultures, ibrutinib did not inhibit FcγR-mediated cytokine production despite doing so in single cultures. These results suggest that combining ibrutinib with monoclonal antibody therapy could enhance chronic lymphocytic leukemia cell killing without affecting macrophage effector function. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Molecular Analysis of the Locus Responsible for Production of Plantaricin S, a Two-Peptide Bacteriocin Produced by Lactobacillus plantarum LPCO10

PubMed Central

Stephens, Sarah K.; Floriano, Belén; Cathcart, Declan P.; Bayley, Susan A.; Witt, Valerie F.; Jiménez-Díaz, Rufino; Warner, Philip J.; Ruiz-Barba, José Luis

1998-01-01

A 4.5-kb region of chromosomal DNA carrying the locus responsible for the production of plantaricin S, a two-peptide bacteriocin produced by Lactobacillus plantarum LPCO10 (R. Jiménez-Díaz, J. L. Ruiz-Barba, D. P. Cathcart, H. Holo, I. F. Nes, K. H. Sletten, and P. J. Warner, Appl. Environ. Microbiol. 61:4459–4463, 1995), has been cloned, and the nucleotide sequence has been elucidated. Two genes, designated plsA and plsB and encoding peptides α and β, respectively, of plantaricin S, plus an open reading frame (ORF), ORF2, were found to be organized in an operon. Northern blot analysis showed that these genes are cotranscribed, giving a ca. 0.7-kb mRNA, whose transcription start point was determined by primer extension. Nucleotide sequences of plsA and plsB revealed that both genes are translated as bacteriocin precursors which include N-terminal leader sequences of the double-glycine type. The role of ORF2 is unknown at the moment, although it might be expected to encode an immunity protein of the type described for other bacteriocin operons. In addition, several other potential ORFs have been found, including some which may be responsible for the regulation of bacteriocin production. Two of them, ORF8 and ORF14, show strong homology with histidine protein kinase and response regulator genes, respectively, which have been found to be involved in the regulation of the production of other bacteriocins from lactic acid bacteria. A third ORF, ORF5, shows homology with gene agrB from Staphylococcus aureus, which is involved in the mechanism of regulation of the virulence phenotype in this species. Thus, an agr-like regulatory system for the production of plantaricin S is postulated. PMID:9572965

Ovocalyxin-36 is an effector protein modulating the production of proinflammatory mediators.

PubMed

Kovacs-Nolan, Jennifer; Cordeiro, Cristianne; Young, Denise; Mine, Yoshinori; Hincke, Maxwell

2014-07-15

Sepsis is a systemic inflammatory response syndrome during infection. Therapeutic agents are essential to protect the host from sepsis. Ovocalyxin-36 (OCX-36) is a chicken eggshell membrane protein and shares protein sequence and gene organization homology with bactericidal permeability-increasing protein (BPI), lipopolysaccharide-binding protein (LBP) and palate, lung and nasal epithelium clone (PLUNC) proteins that play a major role in innate immune protection. We recently reported that OCX-36 binds to both lipopolysaccharide (LPS) and lipoteichoic acid (LTA) (Cordeiro et al., 2013, PLoS ONE 8, e84112), which is an important activity to neutralize endotoxins and non-endotoxin pyrogens during an inflammatory response. Here we investigated the immune modulating effects of OCX-36 and enzymatically digested OCX-36 (dOCX-36) in vitro and in a mouse model of endotoxemia. OCX-36 alone dose-dependently induced both TNF-α and nitric oxide (NO) production by RAW 264.7 macrophage cells, and this immunostimulatory effect was reduced by enzymatic digestion. In the presence of LPS, dOCX-36 was more effective than intact OCX-36 at reducing LPS-induced secretion of TNF-α from RAW 264.7 cells, but did not reduce NO production. In contrast, OCX-36 increased LPS-induced NO production, both in the presence and absence of FBS, PCR array analysis confirmed that OCX-36 and dOCX-36 differentially regulated genes involved in innate immunity, and dOCX-36 down-regulated the expression of genes involved in LPS signaling and inflammatory responses. In vivo, dOCX-36 was more effective at reducing LPS-induced inflammatory symptoms and inhibiting the local production of pro-inflammatory mediators in the small intestine. These results suggest that OCX-36 and OCX-36 derived peptides may differentially modulate innate immune responses, and support our hypothesis that OCX-36 derived peptides have potential therapeutic applications in sepsis. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Direct Visualization of Mucus Production by the Cold-Water Coral Lophelia pertusa with Digital Holographic Microscopy

PubMed Central

Zetsche, Eva-Maria; Baussant, Thierry; Meysman, Filip J. R.; van Oevelen, Dick

2016-01-01

Lophelia pertusa is the dominant reef-building organism of cold-water coral reefs, and is known to produce significant amounts of mucus, which could involve an important metabolic cost. Mucus is involved in particle removal and feeding processes, yet the triggers and dynamics of mucus production are currently still poorly described because the existing tools to study these processes are not appropriate. Using a novel microscopic technique—digital holographic microscopy (DHM)–we studied the mucus release of L. pertusa under various experimental conditions. DHM technology permits μm-scale observations and allows the visualization of transparent mucoid substances in real time without staining. Fragments of L. pertusa were first maintained in flow-through chambers without stressors and imaged with DHM, then exposed to various stressors (suspended particles, particulate food and air exposure) and re-imaged. Under non-stressed conditions no release of mucus was observed, whilst mucus strings and sheaths were produced in response to suspended particles (activated charcoal and drill cuttings sediment) i.e. in a stressed condition. Mucus strings and so-called ‘string balls’ were also observed in response to exposure to particulate food (brine shrimp Artemia salina). Upon air-exposure, mucus production was clearly visible once the fragments were returned to the flow chamber. Distinct optical properties such as optical path length difference (OPD) were measured with DHM in response to the various stimuli suggesting that different mucus types are produced by L. pertusa. Mucus produced to reject particles is similar in refractive index to the surrounding seawater, suggesting that the energy content of this mucus is low. In contrast, mucus produced in response to either food particle addition or air exposure had a higher refractive index, suggesting a higher metabolic investment in the production of these mucoid substances. This paper shows for the first time the potential of DHM technology for the detection, characterization and quantification of mucus production through OPD measurements in L. pertusa. PMID:26840074

A mitochondrial NADH-dependent fumarate reductase involved in the production of succinate excreted by procyclic Trypanosoma brucei.

PubMed

Coustou, Virginie; Besteiro, Sébastien; Rivière, Loïc; Biran, Marc; Biteau, Nicolas; Franconi, Jean-Michel; Boshart, Michael; Baltz, Théo; Bringaud, Frédéric

2005-04-29

Trypanosoma brucei is a parasitic protist responsible for sleeping sickness in humans. The procyclic stage of T. brucei expresses a soluble NADH-dependent fumarate reductase (FRDg) in the peroxisome-like organelles called glycosomes. This enzyme is responsible for the production of about 70% of the excreted succinate, the major end product of glucose metabolism in this form of the parasite. Here we functionally characterize a new gene encoding FRD (FRDm1) expressed in the procyclic stage. FRDm1 is a mitochondrial protein, as evidenced by immunolocalization, fractionation of digitonin-permeabilized cells, and expression of EGFP-tagged FRDm1 in the parasite. RNA interference was used to deplete FRDm1, FRDg, or both together. The analysis of the resulting mutant cell lines showed that FRDm1 is responsible for 30% of the cellular NADH-FRD activity, which solves a long standing debate regarding the existence of a mitochondrial FRD in trypanosomatids. FRDg and FRDm1 together account for the total NADH-FRD activity in procyclics, because no activity was measured in the double mutant lacking expression of both proteins. Analysis of the end products of 13C-enriched glucose excreted by these mutant cell lines showed that FRDm1 contributes to the production of between 14 and 44% of the succinate excreted by the wild type cells. In addition, depletion of one or both FRD enzymes results in up to 2-fold reduction of the rate of glucose consumption. We propose that FRDm1 is involved in the maintenance of the redox balance in the mitochondrion, as proposed for the ancestral soluble FRD presumably present in primitive anaerobic cells.

A bilateral cortical network responds to pitch perturbations in speech feedback

PubMed Central

Kort, Naomi S.; Nagarajan, Srikantan S.; Houde, John F.

2014-01-01

Auditory feedback is used to monitor and correct for errors in speech production, and one of the clearest demonstrations of this is the pitch perturbation reflex. During ongoing phonation, speakers respond rapidly to shifts of the pitch of their auditory feedback, altering their pitch production to oppose the direction of the applied pitch shift. In this study, we examine the timing of activity within a network of brain regions thought to be involved in mediating this behavior. To isolate auditory feedback processing relevant for motor control of speech, we used magnetoencephalography (MEG) to compare neural responses to speech onset and to transient (400ms) pitch feedback perturbations during speaking with responses to identical acoustic stimuli during passive listening. We found overlapping, but distinct bilateral cortical networks involved in monitoring speech onset and feedback alterations in ongoing speech. Responses to speech onset during speaking were suppressed in bilateral auditory and left ventral supramarginal gyrus/posterior superior temporal sulcus (vSMG/pSTS). In contrast, during pitch perturbations, activity was enhanced in bilateral vSMG/pSTS, bilateral premotor cortex, right primary auditory cortex, and left higher order auditory cortex. We also found speaking-induced delays in responses to both unaltered and altered speech in bilateral primary and secondary auditory regions, the left vSMG/pSTS and right premotor cortex. The network dynamics reveal the cortical processing involved in both detecting the speech error and updating the motor plan to create the new pitch output. These results implicate vSMG/pSTS as critical in both monitoring auditory feedback and initiating rapid compensation to feedback errors. PMID:24076223

How the NWC handles software as product

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

Vinson, D.

1997-11-01

This tutorial provides a hands-on view of how the Nuclear Weapons Complex project should be handling (or planning to handle) software as a product in response to Engineering Procedure 401099. The SQAS has published the document SQAS96-002, Guidelines for NWC Processes for Handling Software Product, that will be the basis for the tutorial. The primary scope of the tutorial is on software products that result from weapons and weapons-related projects, although the information presented is applicable to many software projects. Processes that involve the exchange, review, or evaluation of software product between or among NWC sites, DOE, and external customersmore » will be described.« less

Cholera Toxin Production during Anaerobic Trimethylamine N-Oxide Respiration Is Mediated by Stringent Response in Vibrio cholerae*

PubMed Central

Oh, Young Taek; Park, Yongjin; Yoon, Mi Young; Bari, Wasimul; Go, Junhyeok; Min, Kyung Bae; Raskin, David M.; Lee, Kang-Mu; Yoon, Sang Sun

2014-01-01

As a facultative anaerobe, Vibrio cholerae can grow by anaerobic respiration. Production of cholera toxin (CT), a major virulence factor of V. cholerae, is highly promoted during anaerobic growth using trimethylamine N-oxide (TMAO) as an alternative electron acceptor. Here, we investigated the molecular mechanisms of TMAO-stimulated CT production and uncovered the crucial involvement of stringent response in this process. V. cholerae 7th pandemic strain N16961 produced a significantly elevated level of ppGpp, the bacterial stringent response alarmone, during anaerobic TMAO respiration. Bacterial viability was impaired, and DNA replication was also affected under the same growth condition, further suggesting that stringent response is induced. A ΔrelA ΔspoT ppGpp overproducer strain produced an enhanced level of CT, whereas anaerobic growth via TMAO respiration was severely inhibited. In contrast, a ppGpp-null strain (ΔrelA ΔspoT ΔrelV) grew substantially better, but produced no CT, suggesting that CT production and bacterial growth are inversely regulated in response to ppGpp accumulation. Bacterial capability to produce CT was completely lost when the dksA gene, which encodes a protein that works cooperatively with ppGpp, was deleted. In the ΔdksA mutant, stringent response growth inhibition was alleviated, further supporting the inverse regulation of CT production and anaerobic growth. In vivo virulence of ΔrelA ΔspoT ΔrelV or ΔdksA mutants was significantly attenuated. The ΔrelA ΔspoT mutant maintained virulence when infected with exogenous TMAO despite its defective growth. Together, our results reveal that stringent response is activated under TMAO-stimulated anaerobic growth, and it regulates CT production in a growth-dependent manner in V. cholerae. PMID:24648517

Involvement of ethylene in gibberellic acid-induced sulfur assimilation, photosynthetic responses, and alleviation of cadmium stress in mustard.

PubMed

Masood, Asim; Khan, M Iqbal R; Fatma, Mehar; Asgher, Mohd; Per, Tasir S; Khan, Nafees A

2016-07-01

The role of gibberellic acid (GA) or sulfur (S) in stimulation of photosynthesis is known. However, information on the involvement of ethylene in GA-induced photosynthetic responses and cadmium (Cd) tolerance is lacking. This work shows that ethylene is involved in S-assimilation, photosynthetic responses and alleviation of Cd stress by GA in mustard (Brassica juncea L.). Plants grown with 200 mg Cd kg(-1) soil were less responsive to ethylene despite high ethylene evolution and showed photosynthetic inhibition. Plants receiving 10 μM GA spraying plus 100 mg S kg(-1) soil supplementation exhibited increased S-assimilation and photosynthetic responses under Cd stress. Application of GA plus S decreased oxidative stress of plants grown with Cd and limited stress ethylene formation to the range suitable for promoting sulfur use efficiency (SUE), glutathione (GSH) production and photosynthesis. The role of ethylene in GA-induced S-assimilation and reversal of photosynthetic inhibition by Cd was substantiated by inhibiting ethylene biosynthesis with the use of aminoethoxyvinylglycine (AVG). The suppression of S-assimilation and photosynthetic responses by inhibiting ethylene in GA plus S treated plants under Cd stress indicated the involvement of ethylene in GA-induced S-assimilation and Cd stress alleviation. The outcome of the study is important to unravel the interaction between GA and ethylene and their role in Cd tolerance in plants. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

NO homeostasis is a key regulator of early nitrate perception and root elongation in maize*

PubMed Central

Quaggiotti, Silvia

2014-01-01

Crop plant development is strongly dependent on nitrogen availability in the soil and on the efficiency of its recruitment by roots. For this reason, the understanding of the molecular events underlying root adaptation to nitrogen fluctuations is a primary goal to develop biotechnological tools for sustainable agriculture. However, knowledge about molecular responses to nitrogen availability is derived mainly from the study of model species. Nitric oxide (NO) has been recently proposed to be implicated in plant responses to environmental stresses, but its exact role in the response of plants to nutritional stress is still under evaluation. In this work, the role of NO production by maize roots after nitrate perception was investigated by focusing on the regulation of transcription of genes involved in NO homeostasis and by measuring NO production in roots. Moreover, its involvement in the root growth response to nitrate was also investigated. The results provide evidence that NO is produced by nitrate reductase as an early response to nitrate supply and that the coordinated induction of non-symbiotic haemoglobins (nsHbs) could finely regulate the NO steady state. This mechanism seems to be implicated on the modulation of the root elongation in response to nitrate perception. Moreover, an improved agar-plate system for growing maize seedlings was developed. This system, which allows localized treatments to be performed on specific root portions, gave the opportunity to discern between localized and systemic effects of nitrate supply to roots. PMID:24220653

NO homeostasis is a key regulator of early nitrate perception and root elongation in maize.

PubMed

Manoli, Alessandro; Begheldo, Maura; Genre, Andrea; Lanfranco, Luisa; Trevisan, Sara; Quaggiotti, Silvia

2014-01-01

Crop plant development is strongly dependent on nitrogen availability in the soil and on the efficiency of its recruitment by roots. For this reason, the understanding of the molecular events underlying root adaptation to nitrogen fluctuations is a primary goal to develop biotechnological tools for sustainable agriculture. However, knowledge about molecular responses to nitrogen availability is derived mainly from the study of model species. Nitric oxide (NO) has been recently proposed to be implicated in plant responses to environmental stresses, but its exact role in the response of plants to nutritional stress is still under evaluation. In this work, the role of NO production by maize roots after nitrate perception was investigated by focusing on the regulation of transcription of genes involved in NO homeostasis and by measuring NO production in roots. Moreover, its involvement in the root growth response to nitrate was also investigated. The results provide evidence that NO is produced by nitrate reductase as an early response to nitrate supply and that the coordinated induction of non-symbiotic haemoglobins (nsHbs) could finely regulate the NO steady state. This mechanism seems to be implicated on the modulation of the root elongation in response to nitrate perception. Moreover, an improved agar-plate system for growing maize seedlings was developed. This system, which allows localized treatments to be performed on specific root portions, gave the opportunity to discern between localized and systemic effects of nitrate supply to roots.

Plant vasculature-mediated signaling involved in early phosphate stress response

USDA-ARS?s Scientific Manuscript database

Depletion of finite global rock phosphate (Pi) reserves will impose major limitations on future agricultural productivity and food security. Hence, modern breeding programs seek to develop Pi-efficient crops with sustainable yields under reduced Pi fertilizer inputs. In this regard, although the lon...

75 FR 29991 - Marine Mammals; receipt of application for permit amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-28

... research on cetacean behavior, sound production, and responses to sound. The research methods include... amendment to Permit No. 14241 to conduct research on marine mammals. ADDRESSES: The application and related... animal hears and measures vocalization, behavior, and physiological parameters. Research also involves...

75 FR 57472 - Clinical Investigator Training Course

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0456... scientific, regulatory, and ethical considerations involved in the conduct of clinical trials. DATES: The... development of medical products. They bear the responsibility for ensuring the safe and ethical treatment of...

Binding of phosphatidic acid to 14-3-3 proteins hampers their ability to activate the plant plasma membrane H+-ATPase.

PubMed

Camoni, Lorenzo; Di Lucente, Cristina; Pallucca, Roberta; Visconti, Sabina; Aducci, Patrizia

2012-08-01

Phosphatidic acid is a phospholipid second messenger implicated in various cellular processes in eukaryotes. In plants, production of phosphatidic acid is triggered in response to a number of biotic and abiotic stresses. Here, we show that phosphatidic acid binds to 14-3-3 proteins, a family of regulatory proteins which bind client proteins in a phosphorylation-dependent manner. Binding of phosphatidic acid involves the same 14-3-3 region engaged in protein target binding. Consequently, micromolar phosphatidic acid concentrations significantly hamper the interaction of 14-3-3 proteins with the plasma membrane H(+)-ATPase, a well characterized plant 14-3-3 target, thus inhibiting the phosphohydrolitic enzyme activity. Moreover, the proton pump is inhibited when endogenous PA production is triggered by phospholipase D and the G protein agonist mastoparan-7. Hence, our data propose a possible mechanism involving PA that regulates 14-3-3-mediated cellular processes in response to stress. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Deciphering early events involved in hyperosmotic stress-induced programmed cell death in tobacco BY-2 cells.

PubMed

Monetti, Emanuela; Kadono, Takashi; Tran, Daniel; Azzarello, Elisa; Arbelet-Bonnin, Delphine; Biligui, Bernadette; Briand, Joël; Kawano, Tomonori; Mancuso, Stefano; Bouteau, François

2014-03-01

Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on early responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca(2+) concentration ([Ca(2+)]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·(-)) generation by NADPH-oxidase. In the case of NaCl, an early influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·(-) generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared early responses, such as [Ca(2+)]cyt increase and singlet oxygen production, do not seem to be involved in PCD.

Circadian expression of steroidogenic cytochromes P450 in the mouse adrenal gland--involvement of cAMP-responsive element modulator in epigenetic regulation of Cyp17a1.

PubMed

Košir, Rok; Zmrzljak, Ursula Prosenc; Bele, Tanja; Acimovic, Jure; Perse, Martina; Majdic, Gregor; Prehn, Cornelia; Adamski, Jerzy; Rozman, Damjana

2012-05-01

The cytochrome P450 (CYP) genes Cyp51, Cyp11a1, Cyp17a1, Cyb11b1, Cyp11b2 and Cyp21a1 are involved in the adrenal production of corticosteroids, whose circulating levels are circadian. cAMP signaling plays an important role in adrenal steroidogenesis. By using cAMP responsive element modulator (Crem) knockout mice, we show that CREM isoforms contribute to circadian expression of steroidogenic CYPs in the mouse adrenal gland. Most striking was the CREM-dependent hypomethylation of the Cyp17a1 promoter at zeitgeber time 12, which resulted in higher Cyp17a1 mRNA and protein expression in the knockout adrenal glands. The data indicate that products of the Crem gene control the epigenetic repression of Cyp17 in mouse adrenal glands. © 2011 The Authors Journal compilation © 2011 FEBS.

Omics Approach to Identify Factors Involved in Brassica Disease Resistance.

PubMed

Francisco, Marta; Soengas, Pilar; Velasco, Pablo; Bhadauria, Vijai; Cartea, Maria E; Rodríguez, Victor M

2016-01-01

Understanding plant's defense mechanisms and their response to biotic stresses is of fundamental meaning for the development of resistant crop varieties and more productive agriculture. The Brassica genus involves a large variety of economically important species and cultivars used as vegetable source, oilseeds, forage and ornamental. Damage caused by pathogens attack affects negatively various aspects of plant growth, development, and crop productivity. Over the last few decades, advances in plant physiology, genetics, and molecular biology have greatly improved our understanding of plant responses to biotic stress conditions. In this regard, various 'omics' technologies enable qualitative and quantitative monitoring of the abundance of various biological molecules in a high-throughput manner, and thus allow determination of their variation between different biological states on a genomic scale. In this review, we have described advances in 'omic' tools (genomics, transcriptomics, proteomics and metabolomics) in the view of conventional and modern approaches being used to elucidate the molecular mechanisms that underlie Brassica disease resistance.

Women and agricultural productivity: Reframing the Issues.

PubMed

Doss, Cheryl R

2018-01-01

Should agricultural development programmes target women in order to increase productivity? This article analyzes the challenges in distinguishing women's agricultural productivity from that of men. Most of the literature compares productivity on plots managed by women with those managed by men, ignoring the majority of agricultural households in which men and women are both involved in management and production. The empirical studies which have been carried out provide scant evidence for where the returns to projects may be highest, in terms of who to target. Yet, programmes that do not consider gendered responsibilities, resources and constraints, are unlikely to succeed, either in terms of increasing productivity or benefitting men and women smallholder farmers.

The dominant allele Aft induces a shift from flavonol to anthocyanin production in response to UV-B radiation in tomato fruit.

PubMed

Catola, Stefano; Castagna, Antonella; Santin, Marco; Calvenzani, Valentina; Petroni, Katia; Mazzucato, Andrea; Ranieri, Annamaria

2017-08-01

The introgression of the A ft allele into domesticated tomato induced a shift from flavonol to anthocyanin production in response to UV-B radiation, while the hp - 1 allele negatively influenced the response of flavonoid biosynthesis to UV-B. Introgression of the dominant allele Anthocyanin fruit (Aft) from Solanum chilense induces anthocyanin accumulation in the peel of tomato (Solanum lycopersicum L.) fruit. UV-B radiation can influence plant secondary metabolism regulating the expression of several genes, among which those involved in flavonoid biosynthesis. Here, we investigated whether post-harvest UV-B treatment could up-regulate flavonoid production in tomato fruits and whether the Aft allele could affect flavonoid biosynthesis under UV-B radiation. Mature green fruits of an anthocyanin-rich tomato mutant line (SA206) and of its wild-type reference, cv. Roma, were daily subjected to post-harvest UV-B treatment until full ripening. Up-regulation of CHS and CHI transcription by UV-B treatment induced flavonoid accumulation in the peel of cv. Roma. Conversely, UV-B decreased the total flavonoid content and CHS transcript levels in the SA206 peel. SA206 being a double mutant containing also hp-1 allele, we investigated also the behavior of hp-1 fruit. The decreased peel flavonoid accumulation and gene transcription in response to UV-B suggest that hp-1 allele is involved in the marked down-regulation of the flavonoid biosynthesis observed in SA206 fruit. Interestingly, in SA206, UV-B radiation promoted the synthesis of delphinidin, petunidin, and malvidin by increasing F3'5'H and DFR transcription, but it decreased rutin production, suggesting a switch from flavonols to anthocyanins. Finally, although UV-B radiation does not reach the inner fruit tissues, it down-regulated flavonoid biosynthesis in the flesh of both genotypes. This study provides, for the first time, evidence that the presence of the functional Aft allele, under UV-B radiation, redirects flavonoid synthesis towards anthocyanin production and suggests that the hp-1 allele negatively influences the response of flavonoid biosynthesis to UV-B.

Metagenomic Analysis of the Sponge Discodermia Reveals the Production of the Cyanobacterial Natural Product Kasumigamide by 'Entotheonella'.

PubMed

Nakashima, Yu; Egami, Yoko; Kimura, Miki; Wakimoto, Toshiyuki; Abe, Ikuro

2016-01-01

Sponge metagenomes are a useful platform to mine cryptic biosynthetic gene clusters responsible for production of natural products involved in the sponge-microbe association. Since numerous sponge-derived bioactive metabolites are biosynthesized by the symbiotic bacteria, this strategy may concurrently reveal sponge-symbiont produced compounds. Accordingly, a metagenomic analysis of the Japanese marine sponge Discodermia calyx has resulted in the identification of a hybrid type I polyketide synthase-nonribosomal peptide synthetase gene (kas). Bioinformatic analysis of the gene product suggested its involvement in the biosynthesis of kasumigamide, a tetrapeptide originally isolated from freshwater free-living cyanobacterium Microcystis aeruginosa NIES-87. Subsequent investigation of the sponge metabolic profile revealed the presence of kasumigamide in the sponge extract. The kasumigamide producing bacterium was identified as an 'Entotheonella' sp. Moreover, an in silico analysis of kas gene homologs uncovered the presence of kas family genes in two additional bacteria from different phyla. The production of kasumigamide by distantly related multiple bacterial strains implicates horizontal gene transfer and raises the potential for a wider distribution across other bacterial groups.

From problem people to addictive products: a qualitative study on rethinking gambling policy from the perspective of lived experience.

PubMed

Miller, Helen E; Thomas, Samantha L; Robinson, Priscilla

2018-04-06

Previous research has shown that government and industry discussions of gambling may focus on personal responsibility for gambling harm. In Australia, these discussions have largely excluded people with lived experience of problem gambling, including those involved in peer support and advocacy. We conducted 26 in-depth interviews with people with current or previous problem gambling on electronic gaming machines (EGMs) involved in peer support and advocacy activities, using an approach informed by Interpretive Policy Analysis and Constructivist Grounded Theory. Participants perceived that government and industry discussed gambling as safe and entertaining with a focus on personal responsibility for problem gambling. This focus on personal responsibility was perceived to increase stigma associated with problem gambling. In contrast, they described gambling as risky, addictive and harmful, with problem gambling resulting from the design of EGMs. As a result of their different perspectives, participants proposed different interventions to reduce gambling harm, including reducing accessibility and making products safer. Challenging the discourses used by governments and industry to describe gambling, using the lived experience of people with experience of gambling harm, may result in reduced stigma associated with problem gambling, and more effective public policy approaches to reducing harm.

United States Department of Energy Environmental Restoration and Waste Management: Comment Response Document

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

Not Available

IN 1989, Secretary of Energy James Watkins called for a fundamental change in the way US Department of Energy (DOE) meets its environmental responsibilities. Whereas DOE had long subordinated environmental concerns to the higher priority of weapons production, the Department's mission was restructured to place less emphasis on defense-related production and much greater emphasis on sound environmental management and restoration of its weapons complex. To carry out this new mission, the Office of Environmental Restoration and Waste Management (EM) was created. Secretary Watkins further stressed that DOE's new commitment to environmental values will be carried out under a new DOEmore » culture-one of openness, responsiveness, and accountability. The Environmental Restoration and Waste Management Five-Year Plan is the key planning document that embodies both the new DOE emphasis on environmental management and the Department's commitment to involving the public in its planning process. Updated annually, the Five-Year Plan guides EM's efforts to clean up DOE facilities and manage its waste -- its accomplishments, goals, and planned activities -- and reinforces DOE's commitment to the culture change by involving the general public in its development.« less

United States Department of Energy Environmental Restoration and Waste Management: Comment Response Document. Five-Year Plan, Fiscal Years 1993--1997

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

Not Available

IN 1989, Secretary of Energy James Watkins called for a fundamental change in the way US Department of Energy (DOE) meets its environmental responsibilities. Whereas DOE had long subordinated environmental concerns to the higher priority of weapons production, the Department`s mission was restructured to place less emphasis on defense-related production and much greater emphasis on sound environmental management and restoration of its weapons complex. To carry out this new mission, the Office of Environmental Restoration and Waste Management (EM) was created. Secretary Watkins further stressed that DOE`s new commitment to environmental values will be carried out under a new DOEmore » culture-one of openness, responsiveness, and accountability. The Environmental Restoration and Waste Management Five-Year Plan is the key planning document that embodies both the new DOE emphasis on environmental management and the Department`s commitment to involving the public in its planning process. Updated annually, the Five-Year Plan guides EM`s efforts to clean up DOE facilities and manage its waste -- its accomplishments, goals, and planned activities -- and reinforces DOE`s commitment to the culture change by involving the general public in its development.« less

Interleukin 4 receptor signaling in human monocytes and U937 cells involves the activation of a phosphatidylcholine-specific phospholipase C: a comparison with chemotactic peptide, FMLP, phospholipase D, and sphingomyelinase

PubMed Central

1994-01-01

Interleukin 4 (IL-4) diminishes cytokine activation of human macrophage. IL-4 binding to monocyte IL-4R is associated with protein kinase C (PKC) translocation to a nuclear fraction. The cleavage of diacyglycerol (DAG), an activator of PKC, from membrane phospholipids was investigated to define the proximal events of IL-4R signaling. IL-4 induced a statistically significant time-and dose-dependent generation of DAG. The IL-4-triggered production of DAG was not derived from phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis, since neither cytosolic calcium flux nor liberation of inositol phosphates was detected in response to IL-4. Experiments were performed using [14C- methyl]choline-labeled U937 cells and monocytes to determine whether IL- 4R activated phospholipase C (PLC), PLD, or PLA2 to use membrane phosphatidylcholine (PC) to form DAG. IL-4 induced a time- and dose- dependent increase of phosphocholine (pchol) with concomitant degradation of membrane PC (p < 0.05 compared with control). The finding that the peak reduction of PC was equivalent to peak production of pchol suggested that IL-4R signaling involved the activation of a PC- specific PLC. Changes in choline (chol) or lyso-PC and glycerolphosphocholine, the respective products of PC cleavage by PLD or PLA2, were not detected in IL-4-treated cells. In contrast, exogenous PLD induced an increase in chol and concomitant loss of membrane PC. Additional investigation suggested that IL-4R signaling does not involve PLD. In cells labeled with L-lyso-3-PC 1-[1- 14C]palmitoyl, PLD but not IL-4, increased the production of phosphatidic acid (PA) and phosphatidyl-ethanol when pretreated with ethanol. Propranolol, an inhibitor of phosphatidate phosphohydrolase, and calyculin A, a phosphatase 1 and 2A inhibitor, blocked DAG production in response to FMLP but not to IL-4. In propranolol pretreated cells, PMA but not IL-4 triggered the production of PA and lowered the amount of DAG. Evidence that PLA2 is not coupled to IL-4R is the detection of arachidonate production in response to FMLP but not to IL-4. Furthermore, IL-4R is not coupled to sphingomyelinase (SMase) since IL-4, unlike exogenous SMase, did not generate ceramide but induced the hydrolysis of PC to pchol that was comparable to exogenous PLC. In summary, IL-4R signaling in monocytes and U937 cells involves PLC and not PLD, PLA2, or SMase, and it uses PC and not PIP2 to form DAG. PMID:7931078

Developmental changes in brain activation involved in the production of novel speech sounds in children.

PubMed

Hashizume, Hiroshi; Taki, Yasuyuki; Sassa, Yuko; Thyreau, Benjamin; Asano, Michiko; Asano, Kohei; Takeuchi, Hikaru; Nouchi, Rui; Kotozaki, Yuka; Jeong, Hyeonjeong; Sugiura, Motoaki; Kawashima, Ryuta

2014-08-01

Older children are more successful at producing unfamiliar, non-native speech sounds than younger children during the initial stages of learning. To reveal the neuronal underpinning of the age-related increase in the accuracy of non-native speech production, we examined the developmental changes in activation involved in the production of novel speech sounds using functional magnetic resonance imaging. Healthy right-handed children (aged 6-18 years) were scanned while performing an overt repetition task and a perceptual task involving aurally presented non-native and native syllables. Productions of non-native speech sounds were recorded and evaluated by native speakers. The mouth regions in the bilateral primary sensorimotor areas were activated more significantly during the repetition task relative to the perceptual task. The hemodynamic response in the left inferior frontal gyrus pars opercularis (IFG pOp) specific to non-native speech sound production (defined by prior hypothesis) increased with age. Additionally, the accuracy of non-native speech sound production increased with age. These results provide the first evidence of developmental changes in the neural processes underlying the production of novel speech sounds. Our data further suggest that the recruitment of the left IFG pOp during the production of novel speech sounds was possibly enhanced due to the maturation of the neuronal circuits needed for speech motor planning. This, in turn, would lead to improvement in the ability to immediately imitate non-native speech. Copyright © 2014 Wiley Periodicals, Inc.

Redox Regulation of Protein Kinases

PubMed Central

Truong, Thu H.; Carroll, Kate S.

2015-01-01

Protein kinases represent one of the largest families of genes found in eukaryotes. Kinases mediate distinct cellular processes ranging from proliferation, differentiation, survival, and apoptosis. Ligand-mediated activation of receptor kinases can lead to the production of endogenous H2O2 by membrane-bound NADPH oxidases. In turn, H2O2 can be utilized as a secondary messenger in signal transduction pathways. This review presents an overview of the molecular mechanisms involved in redox regulation of protein kinases and its effects on signaling cascades. In the first half, we will focus primarily on receptor tyrosine kinases (RTKs), whereas the latter will concentrate on downstream non-receptor kinases involved in relaying stimulant response. Select examples from the literature are used to highlight the functional role of H2O2 regarding kinase activity, as well as the components involved in H2O2 production and regulation during cellular signaling. In addition, studies demonstrating direct modulation of protein kinases by H2O2 through cysteine oxidation will be emphasized. Identification of these redox-sensitive residues may help uncover signaling mechanisms conserved within kinase subfamilies. In some cases, these residues can even be exploited as targets for the development of new therapeutics. Continued efforts in this field will further basic understanding of kinase redox regulation, and delineate the mechanisms involved in physiologic and pathological H2O2 responses. PMID:23639002

Reactive Oxygen Species Function to Mediate the Fe Deficiency Response in an Fe-Efficient Apple Genotype: An Early Response Mechanism for Enhancing Reactive Oxygen Production

PubMed Central

Sun, Chaohua; Wu, Ting; Zhai, Longmei; Li, Duyue; Zhang, Xinzhong; Xu, Xuefeng; Ma, Huiqin; Wang, Yi; Han, Zhenhai

2016-01-01

Reactive oxygen species (ROS) are important signaling molecules in plants that contribute to stress acclimation. This study demonstrated that ROS play a critical role in Fe deficiency-induced signaling at an early stage in Malus xiaojinensis. Once ROS production has been initiated, prolonged Fe starvation leads to activation of ROS scavenging mechanisms. Further, we demonstrated that ROS scavengers are involved in maintaining the cellular redox homeostasis during prolonged Fe deficiency treatment. Taken together, our results describe a feedback repression loop for ROS to preserve redox homeostasis and maintain a continuous Fe deficiency response in the Fe-efficient woody plant M. xiaojinensis. More broadly, this study reveals a new mechanism in which ROS mediate both positive and negative regulation of plant responses to Fe deficiency stress. PMID:27899933

HIV-1 gp120 envelope glycoprotein determinants for cytokine burst in human monocytes

PubMed Central

Coutu, Mathieu; Prévost, Jérémie; Brassard, Nathalie; Peres, Adam; Stegen, Camille; Madrenas, Joaquín; Kaufmann, Daniel E.; Finzi, Andrés

2017-01-01

The first step of HIV infection involves the interaction of the gp120 envelope glycoprotein to its receptor CD4, mainly expressed on CD4+ T cells. Besides its role on HIV-1 entry, the gp120 has been shown to be involved in the production of IL-1, IL-6, CCL20 and other innate response cytokines by bystander, uninfected CD4+ T cells and monocytes. However, the gp120 determinants involved in these functions are not completely understood. Whether signalling leading to cytokine production is due to CD4 or other receptors is still unclear. Enhanced chemokine receptor binding and subsequent clustering receptors may lead to cytokine production. By using a comprehensive panel of gp120 mutants, here we show that CD4 binding is mandatory for cytokine outburst in monocytes. Our data suggest that targeting monocytes in HIV-infected patients might decrease systemic inflammation and the potential tissue injury associated with the production of inflammatory cytokines. Understanding how gp120 mediates a cytokine burst in monocytes might help develop new approaches to improve the chronic inflammation that persists in these patients despite effective suppression of viremia by antiretroviral therapy. PMID:28346521

Immune response of the Caribbean sea fan, Gorgonia ventalina, exposed to an Aplanochytrium parasite as revealed by transcriptome sequencing

PubMed Central

Burge, Colleen A.; Mouchka, Morgan E.; Harvell, C. Drew; Roberts, Steven

2013-01-01

Coral reef communities are undergoing marked declines due to a variety of stressors including disease. The sea fan coral, Gorgonia ventalina, is a tractable study system to investigate mechanisms of immunity to a naturally occurring pathogen. Functional studies in Gorgonia ventalina immunity indicate that several key pathways and cellular components are involved in response to natural microbial invaders, although to date the functional and regulatory pathways remain largely un-described. This study used short-read sequencing (Illumina GAIIx) to identify genes involved in the response of G. ventalina to a naturally occurring Aplanochytrium spp. parasite. De novo assembly of the G. ventalina transcriptome yielded 90,230 contigs of which 40,142 were annotated. RNA-Seq analysis revealed 210 differentially expressed genes in sea fans exposed to the Aplanochytrium parasite. Differentially expressed genes involved in immunity include pattern recognition molecules, anti-microbial peptides, and genes involved in wound repair and reactive oxygen species formation. Gene enrichment analysis indicated eight biological processes were enriched representing 36 genes, largely involved with protein translation and energy production. This is the first report using high-throughput sequencing to characterize the host response of a coral to a natural pathogen. Furthermore, we have generated the first transcriptome for a soft (octocoral or non-scleractinian) coral species. Expression analysis revealed genes important in invertebrate innate immune pathways, as well as those whose role is previously un-described in cnidarians. This resource will be valuable in characterizing G. ventalina immune response to infection and co-infection of pathogens in the context of environmental change. PMID:23898300

Industrial Chemistry, Science (Experimental): 5316.07.

ERIC Educational Resources Information Center

Scholz, Robert

This unit of instruction presents some important and interesting processes carried on daily in industry and which result in products with which the student is familiar. The student will be responsible for learning some reactions involving these chemical processes and the quantitative calculations of these reactions. Fractional distillation,…

21 CFR 1271.350 - Reporting.

Code of Federal Regulations, 2011 CFR

2011-04-01

... UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Additional Requirements for Establishments Described in § 1271.10... HCT/P involved, and information on all follow-up actions that have been or will be taken in response...

A Response to Deborah Meier.

ERIC Educational Resources Information Center

Sarason, Seymour

1998-01-01

Meier is no bleeding-heart liberal who oversimplifies difficulties involved in creating classrooms and schools reflective of productive learning contexts. Larger system of school governance is inimical to creating such contexts. In his book "How Schools Might Be Governed and Why" (Teacher's College Press, 1997), author argues that the…

Branched-chain amino acid supplementation and the immune response of long-distance athletes.

PubMed

Bassit, Reinaldo A; Sawada, Letícia A; Bacurau, Reury F P; Navarro, Franciso; Martins, Eivor; Santos, Ronaldo V T; Caperuto, Erico C; Rogeri, Patrícia; Costa Rosa, Luís F B P

2002-05-01

Intense long-duration exercise has been associated with immunosuppression, which affects natural killer cells, lymphokine-activated killer cells, and lymphocytes. The mechanisms involved, however, are not fully determined and seem to be multifactorial, including endocrine changes and alteration of plasma glutamine concentration. Therefore, we evaluated the effect of branched-chain amino acid supplementation on the immune response of triathletes and long-distance runners. Peripheral blood was collected prior to and immediately after an Olympic Triathlon or a 30k run. Lymphocyte proliferation, cytokine production by cultured cells, and plasma glutamine were measured. After the exercise bout, athletes from the placebo group presented a decreased plasma glutamine concentration that was abolished by branched-chain amino acid supplementation and an increased proliferative response in their peripheral blood mononuclear cells. Those cells also produced, after exercise, less tumor necrosis factor, interleukins-1 and -4, and interferon and 48% more interleukin-2. Supplementation stimulated the production of interleukin-2 and interferon after exercise and a more pronounced decrease in the production of interleukin-4, indicating a diversion toward a Th1 type immune response. Our results indicate that branched-chain amino acid (BCAA) supplementation recovers the ability of peripheral blood mononuclear cells proliferate in response to mitogens after a long distance intense exercise, as well as plasma glutamine concentration. The amino acids also modify the pattern of cytokine production leading to a diversion of the immune response toward a Th1 type of immune response.

FBXW7 protein has dual-role as tumor suppressor and inflammatory pathway inhibitor | Center for Cancer Research

Cancer.gov

Toll-like receptors (TLRs) are largely responsible for inducing innate immune responses to infection. TLR4 binds lipopolysaccharide (LPS) from Gram-negative bacteria and initiates a signaling pathway to activate inflammatory responses. TLR4 plays a role in diseases such as sepsis and chronic inflammatory disorders. In tumor cells, TLR4 is involved in dampening immune surveillance, and increasing proliferation, inflammatory cytokine production, and invasive migration. Determining how TLR4 expression and signaling is regulated may enable these adverse conditions to be better managed.

Carbon Sources Influence Fumonisin Production in Fusarium proliferatum.

PubMed

Li, Taotao; Gong, Liang; Jiang, Guoxiang; Wang, Yong; Gupta, Vijai Kumar; Qu, Hongxia; Duan, Xuewu; Wang, Jiasheng; Jiang, Yueming

2017-10-01

Fusarium proliferatum is a worldwide fungal pathogen that produces fumonisins which are harmful to animal and human health. However, environmental factors affecting fumonisin biosynthesis in F. proliferatum are not well understood. Based on our preliminary results, in this study, we investigated the effect of sucrose or mannose as the sole carbon source on fumonisin B (FB) production by F. proliferatum and studied their underlying mechanisms via proteome and gene expression analysis. Our results showed that mannose, used as the sole carbon source, significantly blocked fumonisin B 1 and B 2 production by F. proliferatum as compared with the use of sucrose. Fifty-seven differentially expressed proteins were successfully identified. The downregulated proteins in the mannose-cultured strain were mainly involved in carbon metabolism, response to stress, and methionine metabolism, as compared with the sucrose-cultured strain. Moreover, quantitative real-time PCR analysis indicated that expression of several key genes involved in FB biosynthetic pathway and in transcription regulation were significantly downregulated in the mannose-cultured F. proliferatum, whereas expression of histone deacetylation-related genes were significantly upregulated. These results suggested that the blockage of FB biosynthesis by mannose was associated with the decreases in conversion of acetyl-CoA to polyketide, methionine biosynthesis, and NADPH regeneration. More importantly, milder oxidative stress, downregulated expression of genes involved in biosynthetic pathway and transcription regulation, and upregulated expression of genes with histone deacetylation possibly were responsible for the blockage of FB biosynthesis in F. proliferatum. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Precision Metabolic Engineering: the Design of Responsive, Selective, and Controllable Metabolic Systems

PubMed Central

McNerney, Monica P.; Watstein, Daniel M.; Styczynski, Mark P.

2015-01-01

Metabolic engineering is generally focused on static optimization of cells to maximize production of a desired product, though recently dynamic metabolic engineering has explored how metabolic programs can be varied over time to improve titer. However, these are not the only types of applications where metabolic engineering could make a significant impact. Here, we discuss a new conceptual framework, termed “precision metabolic engineering,” involving the design and engineering of systems that make different products in response to different signals. Rather than focusing on maximizing titer, these types of applications typically have three hallmarks: sensing signals that determine the desired metabolic target, completely directing metabolic flux in response to those signals, and producing sharp responses at specific signal thresholds. In this review, we will first discuss and provide examples of precision metabolic engineering. We will then discuss each of these hallmarks and identify which existing metabolic engineering methods can be applied to accomplish those tasks, as well as some of their shortcomings. Ultimately, precise control of metabolic systems has the potential to enable a host of new metabolic engineering and synthetic biology applications for any problem where flexibility of response to an external signal could be useful. PMID:26189665

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

PubMed Central

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

2017-01-01

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

Steroid Hormones and Uterine Vascular Adaptation to Pregnancy

PubMed Central

Chang, Katherine; Zhang, Lubo

2008-01-01

Pregnancy is a physiological state that involves a significant decrease in uterine vascular tone and an increase in uterine blood flow, which is mediated in part by steroid hormones, including estrogen, progesterone, and cortisol. Previous studies have demonstrated the involvement of these hormones in the regulation of uterine artery contractility through signaling pathways specific to the endothelium and the vascular smooth muscle. Alterations in endothelial nitric oxide synthase expression and activity, nitric oxide production, and expression of enzymes involved in PGI2 production contribute to the uterine artery endothelium-specific responses. Steroid hormones also have an effect on calcium-activated potassium channel activity, PKC signaling pathway and myogenic tone, and alterations in pharmacomechanical coupling in the uterine artery smooth muscle. This review addresses current understanding of the molecular mechanisms by which steroid hormones including estrogen, progesterone, and cortisol modulate uterine artery contractility to alter uterine blood flow during pregnancy with an emphasis on the pregnant ewe model. PMID:18497342

Involvement of purinergic signaling on nitric oxide production by neutrophils stimulated with Trichomonas vaginalis.

PubMed

Frasson, Amanda Piccoli; De Carli, Geraldo Attilio; Bonan, Carla Denise; Tasca, Tiana

2012-03-01

Trichomonas vaginalis is a parasite from the human urogenital tract that causes trichomonosis, the most prevalent non-viral sexually transmitted disease. The neutrophil infiltration has been considered to be primarily responsible for cytological changes observed at infection site, and the chemoattractants can play an important role in this leukocytic recruitment. Nitric oxide (NO) is one of the most widespread mediator compounds, and it is implicated in modulation of immunological mechanisms. Extracellular nucleotides and nucleosides are signaling molecules involved in several processes, including immune responses and control of leukocyte trafficking. Ectonucleoside triphosphate diphosphohydrolase members, ecto-5'-nucleotidase, and adenosine deaminase (ectoADA) have been characterized in T. vaginalis. Herein, we investigated the effects of purinergic system on NO production by neutrophils stimulated with T. vaginalis. The trophozoites were able to induce a high NO synthesis by neutrophils through iNOS pathway. The extracellular nucleotides ATP, ADP, and ATPγS (a non-hydrolyzable ATP analog) showed no significant change in NO secretion. In contrast, adenosine and its degradation product, inosine, promoted a low production of the compound. The immunosuppressive effect of adenosine upon NO release by neutrophils occurred due to adenosine A(2A) receptor activation. The ecto-5'-nucleotidase activity displayed by T. vaginalis was shown to be important in adenosine generation, indicating the efficiency of purinergic cascade. Our data suggest the influence of purinergic signaling, specifically adenosinergic system, on NO production by neutrophils in T. vaginalis infection, contributing to the immunological aspects of disease.

Accessory Factors of Cytoplasmic Viral RNA Sensors Required for Antiviral Innate Immune Response.

PubMed

Oshiumi, Hiroyuki; Kouwaki, Takahisa; Seya, Tsukasa

2016-01-01

Type I interferon (IFN) induces many antiviral factors in host cells. RIG-I-like receptors (RLRs) are cytoplasmic viral RNA sensors that trigger the signal to induce the innate immune response that includes type I IFN production. RIG-I and MDA5 are RLRs that form nucleoprotein filaments along viral double-stranded RNA, resulting in the activation of MAVS adaptor molecule. The MAVS protein forms a prion-like aggregation structure, leading to type I IFN production. RIG-I and MDA5 undergo post-translational modification. TRIM25 and Riplet ubiquitin ligases deliver a K63-linked polyubiquitin moiety to the RIG-I N-terminal caspase activation and recruitment domains (CARDs) and C-terminal region; the polyubiquitin chain then stabilizes the two-CARD tetramer structure required for MAVS assembly. MDA5 activation is regulated by phosphorylation. RIOK3 is a protein kinase that phosphorylates the MDA5 protein in a steady state, and PP1α/γ dephosphorylate this protein, resulting in its activation. RIG-I and MDA5 require cytoplasmic RNA helicases for their efficient activation. LGP2, another RLR, is an RNA helicase involved in RLR signaling. This protein does not possess N-terminal CARDs and, thus, cannot trigger downstream signaling by itself. Recent studies have revealed that this protein modulates MDA5 filament formation, resulting in enhanced type I IFN production. Several other cytoplasmic RNA helicases are involved in RLR signaling. DDX3, DHX29, DHX36, and DDX60 RNA helicases have been reported to be involved in RLR-mediated type I IFN production after viral infection. However, the underlying mechanism is largely unknown. Future studies are required to reveal the role of RNA helicases in the RLR signaling pathway.

A case for increased private sector involvement in Ireland's national animal health services

PubMed Central

2008-01-01

Non-regulatory animal health issues, such as Johne's disease, infectious bovine rhinotracheitis (IBR) and mastitis will become increasing important, with ongoing globalisation of markets in animals and animal products. In response, Ireland may need to broaden the scope of its national animal health services. However, there have been concerns about the respective roles and responsibilities (both financial and otherwise) of government and industry in any such moves. This paper argues the case for increased private sector involvement in Ireland's national animal health services, based both on theoretical considerations and country case studies (the Netherlands and Australia). The Dutch and Australian case studies present examples of successful partnerships between government and industry, including systems and processes to address non-regulatory animal health issues. In each case, the roles and responsibilities of government are clear, as are the principles underpinning government involvement. Furthermore, the roles and responsibilities (financial and otherwise) of the Dutch and Australian industry are determined through enabling legislation, providing both legitimacy and accountability. There are constraints on the use of EU and national government funds to support non-regulatory animal health services in EU member states (such as Ireland and the Netherlands). PMID:21851708

Relevance of the two-component sensor protein CiaH to acid and oxidative stress responses in Streptococcus pyogenes.

PubMed

Tatsuno, Ichiro; Isaka, Masanori; Okada, Ryo; Zhang, Yan; Hasegawa, Tadao

2014-03-28

The production of virulence proteins depends on environmental factors, and two-component regulatory systems are involved in sensing these factors. We previously established knockout strains in all suspected two-component regulatory sensor proteins of the emm1 clinical strain of S. pyogenes and examined their relevance to acid stimuli in a natural atmosphere. In the present study, their relevance to acid stimuli was re-examined in an atmosphere containing 5% CO2. The spy1236 (which is identical to ciaHpy) sensor knockout strain showed significant growth reduction compared with the parental strain in broth at pH 6.0, suggesting that the Spy1236 (CiaHpy) two-component sensor protein is involved in acid response of S. pyogenes. CiaH is also conserved in Streptococcus pneumoniae, and it has been reported that deletion of the gene for its cognate response regulator (ciaRpn) made the pneumococcal strains more sensitive to oxidative stress. In this report, we show that the spy1236 knockout mutant of S. pyogenes is more sensitive to oxidative stress than the parental strain. These results suggest that the two-component sensor protein CiaH is involved in stress responses in S. pyogenes.

AtRD22 and AtUSPL1, Members of the Plant-Specific BURP Domain Family Involved in Arabidopsis thaliana Drought Tolerance

PubMed Central

Harshavardhan, Vokkaliga Thammegowda; Van Son, Le; Seiler, Christiane; Junker, Astrid; Weigelt-Fischer, Kathleen; Klukas, Christian; Altmann, Thomas; Sreenivasulu, Nese; Bäumlein, Helmut; Kuhlmann, Markus

2014-01-01

Crop plants are regularly challenged by a range of environmental stresses which typically retard their growth and ultimately compromise economic yield. The stress response involves the reprogramming of approximately 4% of the transcriptome. Here, the behavior of AtRD22 and AtUSPL1, both members of the Arabidopsis thaliana BURP (BNM2, USP, RD22 and polygalacturonase isozyme) domain-containing gene family, has been characterized. Both genes are up-regulated as part of the abscisic acid (ABA) mediated moisture stress response. While AtRD22 transcript was largely restricted to the leaf, that of AtUSPL1 was more prevalent in the root. As the loss of function of either gene increased the plant's moisture stress tolerance, the implication was that their products act to suppress the drought stress response. In addition to the known involvement of AtUSPL1 in seed development, a further role in stress tolerance was demonstrated. Based on transcriptomic data and phenotype we concluded that the enhanced moisture stress tolerance of the two loss-of-function mutants is a consequence of an enhanced basal defense response. PMID:25333723

A case for increased private sector involvement in Ireland's national animal health services.

PubMed

More, Simon J

2008-02-01

Non-regulatory animal health issues, such as Johne's disease, infectious bovine rhinotracheitis (IBR) and mastitis will become increasing important, with ongoing globalisation of markets in animals and animal products. In response, Ireland may need to broaden the scope of its national animal health services. However, there have been concerns about the respective roles and responsibilities (both financial and otherwise) of government and industry in any such moves. This paper argues the case for increased private sector involvement in Ireland's national animal health services, based both on theoretical considerations and country case studies (the Netherlands and Australia). The Dutch and Australian case studies present examples of successful partnerships between government and industry, including systems and processes to address non-regulatory animal health issues. In each case, the roles and responsibilities of government are clear, as are the principles underpinning government involvement. Furthermore, the roles and responsibilities (financial and otherwise) of the Dutch and Australian industry are determined through enabling legislation, providing both legitimacy and accountability. There are constraints on the use of EU and national government funds to support non-regulatory animal health services in EU member states (such as Ireland and the Netherlands).

Supervisory and routine processes in noun and verb generation in nondemented patients with Parkinson's disease.

PubMed

Crescentini, Cristiano; Mondolo, Federica; Biasutti, Emanuele; Shallice, Tim

2008-01-31

Despite the increased comprehension of the role of the basal ganglia in cognitive functions such as learning, attention, and executive functions, the exact implication of these structures in language remains unclear. A specific role of basal ganglia in language has been proposed. Nonetheless, a recent hypothesis gives the basal ganglia a non-language specific role in the inhibition of competing alternatives during later controlled processes of language production. In this study we assessed the production of both nouns and verbs in a population of 20 nondemented patients with Parkinson's disease (NDPD). Aspects of selection demands and stimulus-response association strength were investigated in both tasks. Performance of NDPD patients was compared with that of 20 matched elderly subjects. An impairment in verb production was found in PD patients. A selection effect on verb production was found in PD patients along with a greater effect of stimulus-response association strength. PD patients had the greatest difficulty in situations of weak stimulus-response association strength. A "Task-Relevant-Response" analysis carried out on stimuli (nouns) in condition of free association suggested that verb production happens in the context of strongly activated nouns. This means that, in order to produce a verb a switch has to be done from a task irrelevant to a task relevant response. Our results are in line with the proposed non-language specific involvement of the basal ganglia in the supervisory rather than the routine semantic processes required during lexical retrieval.

NADPH-generating systems in bacteria and archaea

PubMed Central

Spaans, Sebastiaan K.; Weusthuis, Ruud A.; van der Oost, John; Kengen, Servé W. M.

2015-01-01

Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is an essential electron donor in all organisms. It provides the reducing power that drives numerous anabolic reactions, including those responsible for the biosynthesis of all major cell components and many products in biotechnology. The efficient synthesis of many of these products, however, is limited by the rate of NADPH regeneration. Hence, a thorough understanding of the reactions involved in the generation of NADPH is required to increase its turnover through rational strain improvement. Traditionally, the main engineering targets for increasing NADPH availability have included the dehydrogenase reactions of the oxidative pentose phosphate pathway and the isocitrate dehydrogenase step of the tricarboxylic acid (TCA) cycle. However, the importance of alternative NADPH-generating reactions has recently become evident. In the current review, the major canonical and non-canonical reactions involved in the production and regeneration of NADPH in prokaryotes are described, and their key enzymes are discussed. In addition, an overview of how different enzymes have been applied to increase NADPH availability and thereby enhance productivity is provided. PMID:26284036

The time-course of feature interference in agreement comprehension: Multiple mechanisms and asymmetrical attraction

PubMed Central

Tanner, Darren; Nicol, Janet; Brehm, Laurel

2014-01-01

Attraction interference in language comprehension and production may be as a result of common or different processes. In the present paper, we investigate attraction interference during language comprehension, focusing on the contexts in which interference arises and the time-course of these effects. Using evidence from event-related brain potentials (ERPs) and sentence judgment times, we show that agreement attraction in comprehension is best explained as morphosyntactic interference during memory retrieval. This stands in contrast to attraction as a message-level process involving the representation of the subject NP's number features, which is a strong contributor to attraction in production. We thus argue that the cognitive antecedents of agreement attraction in comprehension are non-identical with those of attraction in production, and moreover, that attraction in comprehension is primarily a consequence of similarity-based interference in cue-based memory retrieval processes. We suggest that mechanisms responsible for attraction during language comprehension are a subset of those involved in language production. PMID:25258471

A rapid high-performance liquid chromatography-tandem mass spectrometry assay for unambiguous detection of different milk species employed in cheese manufacturing.

PubMed

Bernardi, Nadia; Benetti, Giuseppe; Haouet, Naceur M; Sergi, Manuel; Grotta, Lisa; Marchetti, Sonia; Castellani, Federica; Martino, Giuseppe

2015-12-01

The aim of the study was to investigate the possibility to differentiate the 4 most important species in Italian dairy industry (cow, buffalo, sheep, and goat), applying a bottom-up proteomic approach to assess the milk species involved in cheese production. Selective peptides were detected in milk to use as markers in cheese products. Trypsin-digested milk samples of cow, sheep, goat, and buffalo, analyzed by HPLC-tandem mass spectrometry provided species-specific peptides, some of them recognized by Mascot software (Matrix Science Ltd., Boston, MA) as derived from well-known species specific proteins. A multianalyte multiple reaction monitoring method, built with these specific peptides, was successfully applied to cheeses with different composition, showing high specificity in detection of species involved. Neither aging nor production method seemed to affect the response, demonstrating that chosen peptides well act as species markers for dairy products. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The time-course of feature interference in agreement comprehension: Multiple mechanisms and asymmetrical attraction.

PubMed

Tanner, Darren; Nicol, Janet; Brehm, Laurel

2014-10-01

Attraction interference in language comprehension and production may be as a result of common or different processes. In the present paper, we investigate attraction interference during language comprehension, focusing on the contexts in which interference arises and the time-course of these effects. Using evidence from event-related brain potentials (ERPs) and sentence judgment times, we show that agreement attraction in comprehension is best explained as morphosyntactic interference during memory retrieval. This stands in contrast to attraction as a message-level process involving the representation of the subject NP's number features, which is a strong contributor to attraction in production. We thus argue that the cognitive antecedents of agreement attraction in comprehension are non-identical with those of attraction in production, and moreover, that attraction in comprehension is primarily a consequence of similarity-based interference in cue-based memory retrieval processes. We suggest that mechanisms responsible for attraction during language comprehension are a subset of those involved in language production.

Halogen bonding and pharmaceutical cocrystals: the case of a widely used preservative.

PubMed

Baldrighi, Michele; Cavallo, Gabriella; Chierotti, Michele R; Gobetto, Roberto; Metrangolo, Pierangelo; Pilati, Tullio; Resnati, Giuseppe; Terraneo, Giancarlo

2013-05-06

3-Iodo-2-propynyl-N-butylcarbamate (IPBC) is an iodinated antimicrobial product used globally as a preservative, fungicide, and algaecide. IPBC is difficult to obtain in pure form as well as to handle in industrial products because it tends to be sticky and clumpy. Here, we describe the preparation of four pharmaceutical cocrystals involving IPBC. The obtained cocrystals have been characterized by X-ray diffraction, solution and solid-state NMR, IR, and DSC analyses. In all the described cases the halogen bond (XB) is the key interaction responsible for the self-assembly of the pharmaceutical cocrystals thanks to the involvement of the 1-iodoalkyne moiety of IPBC, which functions as a very reliable XB-donor, with both neutral and anionic XB-acceptors. Most of the obtained cocrystals have improved properties with respect to the source API, in terms, e.g., of thermal stability. The cocrystal involving the GRAS excipient CaCl2 has superior powder flow characteristics compared to the pure IPBC, representing a promising solution to the handling issues related to the manufacturing of products containing IPBC.

Secondary Agriculture Student Awareness of International Agriculture and Factors Influencing Student Awareness.

ERIC Educational Resources Information Center

Harbstreit, Steven R.; Welton, Richard F.

1992-01-01

Responses from 1,008 of 1,398 secondary agricultural students in Kansas found (1) limited awareness of international agricultural products and policy, geography, and other cultures; and (2) awareness increased among students with higher grades, longer time in agricultural programs, or involvement in supervised occupational experience. (SK)

Productive Academic Talk during Inquiry-Based Science

ERIC Educational Resources Information Center

Gillies, Robyn M.

2013-01-01

This study reports on the types of academic talk that contribute to enhanced explanatory responses, reasoning, problem-solving and learning. The study involved 10 groups of 3-4 students who were provided with one of three linguistic tools (i.e. Cognitive Questioning, Philosophy for Children and Collaborative Strategic Reading (CSR)) to scaffold…

Farms and Learning Partnerships in Farming Systems Projects: A Response to the Challenges of Complexity in Agricultural Innovation

ERIC Educational Resources Information Center

Crawford, Anne; Nettle, Ruth; Paine, Mark; Kabore, Carolyn

2007-01-01

Managing the competing interests of productivity growth, environmental concerns, landscape change and societal expectations presents challenges for agricultural industries. Innovation projects supporting knowledge development to address these challenges often involve partnerships with commercial farms, a methodology which promises much but has…

Copyright: A Guide for Public Humanities Projects. Federation Resources 3.

ERIC Educational Resources Information Center

Rozeen, Mark

As public humanities programs increasingly make use of media products, an understanding of copyrights is essential. Some problems pertaining to copyrights may be alleviated by advanced planning, a clear division of responsibilities, and by using reason to determine that policies are workable and fair. The problem involves a growing…

From Action to English: Reality in the Classroom.

ERIC Educational Resources Information Center

Zuern, Guenther

1982-01-01

Describes use of total physical response as a teaching strategy in English-as-a-second-language classes. Students act out commands from teacher with no initial emphasis on oral production. This approach makes a lesson more real to students and physically involving them makes for more successful learning. (Author/BK)

Biomaterials for tissue engineering: summary

NASA Technical Reports Server (NTRS)

Christenson, L.; Mikos, A. G.; Gibbons, D. F.; Picciolo, G. L.; McIntire, L. V. (Principal Investigator)

1997-01-01

This article summarizes presentations and discussion at the workshop "Enabling Biomaterial Technology for Tissue Engineering," which was held during the Fifth World Biomaterials Congress in May 1996. Presentations covered the areas of material substrate architecture, barrier effects, and cellular response, including analysis of biomaterials challenges involved in producing specific tissue-engineered products.

Encoding of Human Action in Broca's Area

ERIC Educational Resources Information Center

Fazio, Patrik; Cantagallo, Anna; Craighero, Laila; D'Ausilio, Alessandro; Roy, Alice C.; Pozzo, Thierry; Calzolari, Ferdinando; Granieri, Enrico; Fadiga, Luciano

2009-01-01

Broca's area has been considered, for over a century, as the brain centre responsible for speech production. Modern neuroimaging and neuropsychological evidence have suggested a wider functional role is played by this area. In addition to the evidence that it is involved in syntactical analysis, mathematical calculation and music processing, it…

Ca2+ conduction by plant cyclic nucleotide gated channels and associated signaling components in pathogen defense signal transduction cascades.

PubMed

Ma, Wei; Berkowitz, Gerald A

2011-05-01

Ca(2+) elevation in the cytosol is an essential early event during pathogen response signaling cascades. However, the specific ion channels involved in Ca(2+) influx into plant cells, and how Ca(2+) signals are initiated and regulate downstream events during pathogen defense responses, are at present unclear. Plant cyclic nucleotide gated ion channels (CNGCs) provide a pathway for Ca(2+) conductance across the plasma membrane (PM) and facilitate cytosolic Ca(2+) elevation in response to pathogen signals. Recent studies indicate that the recognition of pathogens results in cyclic nucleotide production and the activation of CNGCs, which leads to downstream generation of pivotal signaling molecules (such as nitric oxide (NO)). Calmodulins (CaMs) and CaM-like proteins (CMLs) are also involved in this signaling, functioning as Ca(2+) sensors and mediating the synthesis of NO during the plant pathogen response signaling cascade. In this article, these and other pivotal signaling components downstream from the Ca(2+) signal, such as Ca(2+)-dependent protein kinases (CDPKs) and CaM-binding transcription activators (CAMTAs), are discussed in terms of their involvement in the pathogen response signal transduction cascade. © 2010 The Authors. New Phytologist © 2010 New Phytologist Trust.

Role of thymus-eicosanoids in the immune response.

PubMed

Juzan, M; Hostein, I; Gualde, N

1992-08-01

The present review deals with the role(s) of thymus-eicosanoids in the immune response. It reports the production of cyclooxygenase and lipoxygenase metabolites of arachidonic acid by cells of the thymus microenvironment and the role(s) of these eicosanoids in the differentiation and the maturation of immature T-cells. The possibility that these products may be involved in tolerance to self is discussed. Briefly, it is likely that cells from the monocyte-macrophage lineage which constitute a part of the thymus microenvironment could contribute to the education of immature thymocytes by both presenting self-antigens and producing eicosanoids. Tolerance to self might result from PGE2-driven apoptosis and/or LTB4-induced generation of suppressor cells.

An epigenetic antimalarial resistance mechanism involving parasite genes linked to nutrient uptake.

PubMed

Sharma, Paresh; Wollenberg, Kurt; Sellers, Morgan; Zainabadi, Kayvan; Galinsky, Kevin; Moss, Eli; Nguitragool, Wang; Neafsey, Daniel; Desai, Sanjay A

2013-07-05

Acquired antimalarial drug resistance produces treatment failures and has led to periods of global disease resurgence. In Plasmodium falciparum, resistance is known to arise through genome-level changes such as mutations and gene duplications. We now report an epigenetic resistance mechanism involving genes responsible for the plasmodial surface anion channel, a nutrient channel that also transports ions and antimalarial compounds at the host erythrocyte membrane. Two blasticidin S-resistant lines exhibited markedly reduced expression of clag genes linked to channel activity, but had no genome-level changes. Silencing aborted production of the channel protein and was directly responsible for reduced uptake. Silencing affected clag paralogs on two chromosomes and was mediated by specific histone modifications, allowing a rapidly reversible drug resistance phenotype advantageous to the parasite. These findings implicate a novel epigenetic resistance mechanism that involves reduced host cell uptake and is a worrisome liability for water-soluble antimalarial drugs.

Neural correlates of word production stages delineated by parametric modulation of psycholinguistic variables.

PubMed

Wilson, Stephen M; Isenberg, Anna Lisette; Hickok, Gregory

2009-11-01

Word production is a complex multistage process linking conceptual representations, lexical entries, phonological forms and articulation. Previous studies have revealed a network of predominantly left-lateralized brain regions supporting this process, but many details regarding the precise functions of different nodes in this network remain unclear. To better delineate the functions of regions involved in word production, we used event-related functional magnetic resonance imaging (fMRI) to identify brain areas where blood oxygen level-dependent (BOLD) responses to overt picture naming were modulated by three psycholinguistic variables: concept familiarity, word frequency, and word length, and one behavioral variable: reaction time. Each of these variables has been suggested by prior studies to be associated with different aspects of word production. Processing of less familiar concepts was associated with greater BOLD responses in bilateral occipitotemporal regions, reflecting visual processing and conceptual preparation. Lower frequency words produced greater BOLD signal in left inferior temporal cortex and the left temporoparietal junction, suggesting involvement of these regions in lexical selection and retrieval and encoding of phonological codes. Word length was positively correlated with signal intensity in Heschl's gyrus bilaterally, extending into the mid-superior temporal gyrus (STG) and sulcus (STS) in the left hemisphere. The left mid-STS site was also modulated by reaction time, suggesting a role in the storage of lexical phonological codes.

Supply chain optimization for pediatric perioperative departments.

PubMed

Davis, Janice L; Doyle, Robert

2011-09-01

Economic challenges compel pediatric perioperative departments to reduce nonlabor supply costs while maintaining the quality of patient care. Optimization of the supply chain introduces a framework for decision making that drives fiscally responsible decisions. The cost-effective supply chain is driven by implementing a value analysis process for product selection, being mindful of product sourcing decisions to reduce supply expense, creating logistical efficiency that will eliminate redundant processes, and managing inventory to ensure product availability. The value analysis approach is an analytical methodology for product selection that involves product evaluation and recommendation based on consideration of clinical benefit, overall financial impact, and revenue implications. Copyright © 2011 AORN, Inc. Published by Elsevier Inc. All rights reserved.

Primary atmospheric oxidation mechanism for toluene.

PubMed

Baltaretu, Cristian O; Lichtman, Eben I; Hadler, Amelia B; Elrod, Matthew J

2009-01-08

The products of the primary OH-initiated oxidation of toluene were investigated using the turbulent flow chemical ionization mass spectrometry technique at temperatures ranging from 228 to 298 K. A major dienedial-producing pathway was detected for the first time for toluene oxidation, and glyoxal and methylglyoxal were found to be minor primary oxidation products. The results suggest that secondary oxidation processes involving dienedial and epoxide primary products are likely responsible for previous observations of glyoxal and methylglyoxal products from toluene oxidation. Because the dienedial-producing pathway is a null cycle for tropospheric ozone production and glyoxal and methylglyoxal are important secondary organic aerosol precursors, these new findings have important implications for the modeling of toluene oxidation in the atmosphere.

Biological and clinical implications of herbal medicine and natural products for the treatment of inflammatory bowel disease.

PubMed

Guo, Bao-Jian; Bian, Zhao-Xiang; Qiu, Hong-Cong; Wang, Yi-Tao; Wang, Ying

2017-08-01

Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that includes Crohn's disease (CD) and ulcerative colitis (UC). Homeostasis of various regulatory factors involved with intestinal immunity is disrupted in IBD, including the intestinal epithelial barrier, macrophages, and cellular mediators such as cytokines and chemokines. No successful treatment is currently available for the management of IBD. Natural products and herbal medicines have exhibited efficacy for UC and CD in experimental models and clinical trials with the following activities: (1) maintenance of integrity of the intestinal epithelial barrier, (2) regulation of macrophage activation, (3) modulation of innate and adaptive immune response, and (4) inhibition of TNF-α activity. Here, we discuss the major factors involved in the pathogenesis of IBD and the current development of natural products and herbs for the treatment of IBD. © 2017 New York Academy of Sciences.

Science Operations Management

NASA Astrophysics Data System (ADS)

Squibb, Gael F.

1984-10-01

The operation teams for the Infrared Astronomical Satellite (IRAS) included scientists from the IRAS International Science Team. The scientific decisions on an hour-to-hour basis, as well as the long-term strategic decisions, were made by science team members. The IRAS scientists were involved in the analysis of the instrument performance, the analysis of the quality of the data, the decision to reacquire data that was contaminated by radiation effects, the strategy for acquiring the survey data, and the process for using the telescope for additional observations, as well as the processing decisions required to ensure the publication of the final scientific products by end of flight operations plus one year. Early in the project, two science team members were selected to be responsible for the scientific operational decisions. One, located at the operations control center in England, was responsible for the scientific aspects of the satellite operations; the other, located at the scientific processing center in Pasadena, was responsible for the scientific aspects of the processing. These science team members were then responsible for approving the design and test of the tools to support their responsibilities and then, after launch, for using these tools in making their decisions. The ability of the project to generate the final science data products one year after the end of flight operations is due in a large measure to the active participation of the science team members in the operations. This paper presents a summary of the operational experiences gained from this scientific involvement.

Non-fragrance allergens in specific cosmetic products.

PubMed

Travassos, Ana Rita; Claes, Lieve; Boey, Lies; Drieghe, Jacques; Goossens, An

2011-11-01

Reports about the nature of the ingredients responsible for allergic contact dermatitis caused by specific cosmetic products are scarce. Between January 2000 and December 2010, the specific cosmetic products having caused allergic contact dermatitis, as well as the individual allergenic cosmetic ingredients present in them, were recorded by use of a standardized form. Among 11 different categories of cosmetic product, skin care products, followed by hair care and body-cleansing products, were most often involved. The presence of the allergenic ingredient(s) in a specific cosmetic product was confirmed according to the ingredient label in 959 of 1448 records. Six hundred and twenty-one of 959 concerned non-fragrance components, preservatives being responsible for 58% of them. Reactions to formaldehyde and formaldehyde-releasers were most often correlated with body-cleansing products, particularly 2-bromo-2-nitropropane-1,3-diol and skin care products. They were followed by the methylchloroisothiazolinone/methylisothiazolinone mixture, most frequently found as allergens in hair care and intimate hygiene products, and facial cleansers (in the last category together with diazolidinyl urea). Octocrylene was by far the most frequent (photo)allergen in sun care products. This study provides information on the presence and frequency of allergens in specific causal cosmetic products. © 2011 John Wiley & Sons A/S.

Teleost fish larvae adapt to dietary arachidonic acid supply through modulation of the expression of lipid metabolism and stress response genes.

PubMed

Alves Martins, Dulce; Rocha, Filipa; Martínez-Rodríguez, Gonzalo; Bell, Gordon; Morais, Sofia; Castanheira, Filipa; Bandarra, Narcisa; Coutinho, Joana; Yúfera, Manuel; Conceição, Luís E C

2012-09-01

Dietary fatty acid supply can affect stress response in fish during early development. Although knowledge on the mechanisms involved in fatty acid regulation of stress tolerance is scarce, it has often been hypothesised that eicosanoid profiles can influence cortisol production. Genomic cortisol actions are mediated by cytosolic receptors which may respond to cellular fatty acid signalling. An experiment was designed to test the effects of feeding gilthead sea-bream larvae with four microdiets, containing graded arachidonic acid (ARA) levels (0·4, 0·8, 1·5 and 3·0 %), on the expression of genes involved in stress response (steroidogenic acute regulatory protein, glucocorticoid receptor and phosphoenolpyruvate carboxykinase), lipid and, particularly, eicosanoid metabolism (hormone-sensitive lipase, PPARα, phospholipase A2, cyclo-oxygenase-2 and 5-lipoxygenase), as determined by real-time quantitative PCR. Fish fatty acid phenotypes reflected dietary fatty acid profiles. Growth performance, survival after acute stress and similar whole-body basal cortisol levels suggested that sea-bream larvae could tolerate a wide range of dietary ARA levels. Transcription of all genes analysed was significantly reduced at dietary ARA levels above 0·4 %. Nonetheless, despite practical suppression of phospholipase A2 transcription, higher leukotriene B4 levels were detected in larvae fed 3·0 % ARA, whereas a similar trend was observed regarding PGE2 production. The present study demonstrates that adaptation to a wide range of dietary ARA levels in gilthead sea-bream larvae involves the modulation of the expression of genes related to eicosanoid synthesis, lipid metabolism and stress response. The roles of ARA, other polyunsaturates and eicosanoids as signals in this process are discussed.

Diffusible signal factor (DSF) synthase RpfF of Xylella fastidiosa is a multifunction protein also required for response to DSF.

PubMed

Ionescu, Michael; Baccari, Clelia; Da Silva, Aline Maria; Garcia, Angelica; Yokota, Kenji; Lindow, Steven E

2013-12-01

Xylella fastidiosa, like related Xanthomonas species, employs an Rpf cell-cell communication system consisting of a diffusible signal factor (DSF) synthase, RpfF, and a DSF sensor, RpfC, to coordinate expression of virulence genes. While phenotypes of a ΔrpfF strain in Xanthomonas campestris could be complemented by its own DSF, the DSF produced by X. fastidiosa (XfDSF) did not restore expression of the XfDSF-dependent genes hxfA and hxfB to a ΔrpfF strain of X. fastidiosa, suggesting that RpfF is involved in XfDSF sensing or XfDSF-dependent signaling. To test this conjecture, rpfC and rpfF of X. campestris were replaced by those of X. fastidiosa, and the contribution of each gene to the induction of a X. campestris DSF-dependent gene was assessed. As in X. fastidiosa, XfDSF-dependent signaling required both X. fastidiosa proteins RpfF and RpfC. RpfF repressed RpfC signaling activity, which in turn was derepressed by XfDSF. A mutated X. fastidiosa RpfF protein with two substitutions of glutamate to alanine in its active site was incapable of XfDSF production yet enabled a response to XfDSF, indicating that XfDSF production and the response to XfDSF are two separate functions in which RpfF is involved. This mutant was also hypervirulent to grape, demonstrating the antivirulence effects of XfDSF itself in X. fastidiosa. The Rpf system of X. fastidiosa is thus a novel example of a quorum-sensing signal synthase that is also involved in the response to the signal molecule that it synthesizes.

Diffusible Signal Factor (DSF) Synthase RpfF of Xylella fastidiosa Is a Multifunction Protein Also Required for Response to DSF

PubMed Central

Ionescu, Michael; Baccari, Clelia; Da Silva, Aline Maria; Garcia, Angelica; Yokota, Kenji

2013-01-01

Xylella fastidiosa, like related Xanthomonas species, employs an Rpf cell-cell communication system consisting of a diffusible signal factor (DSF) synthase, RpfF, and a DSF sensor, RpfC, to coordinate expression of virulence genes. While phenotypes of a ΔrpfF strain in Xanthomonas campestris could be complemented by its own DSF, the DSF produced by X. fastidiosa (XfDSF) did not restore expression of the XfDSF-dependent genes hxfA and hxfB to a ΔrpfF strain of X. fastidiosa, suggesting that RpfF is involved in XfDSF sensing or XfDSF-dependent signaling. To test this conjecture, rpfC and rpfF of X. campestris were replaced by those of X. fastidiosa, and the contribution of each gene to the induction of a X. campestris DSF-dependent gene was assessed. As in X. fastidiosa, XfDSF-dependent signaling required both X. fastidiosa proteins RpfF and RpfC. RpfF repressed RpfC signaling activity, which in turn was derepressed by XfDSF. A mutated X. fastidiosa RpfF protein with two substitutions of glutamate to alanine in its active site was incapable of XfDSF production yet enabled a response to XfDSF, indicating that XfDSF production and the response to XfDSF are two separate functions in which RpfF is involved. This mutant was also hypervirulent to grape, demonstrating the antivirulence effects of XfDSF itself in X. fastidiosa. The Rpf system of X. fastidiosa is thus a novel example of a quorum-sensing signal synthase that is also involved in the response to the signal molecule that it synthesizes. PMID:24056101

Resveratrol pretreatment attenuates traumatic brain injury in rats by suppressing NLRP3 inflammasome activation via SIRT1.

PubMed

Zou, Peng; Liu, Xiaoxiao; Li, Gang; Wang, Yangang

2018-02-01

The inflammatory response in the cerebral cortex serves an important role in the progression of secondary injury following traumatic brain injury (TBI). The NLR family pyrin domain containing 3 (NLRP3) inflammasome is necessary for initiating inflammation and is involved in various central nervous system disorders. The aim of the present study was to investigate the neuroprotective effect of resveratrol and elucidate the underlying mechanisms of resveratrol associated regulation of the NLRP3 inflammasome in TBI. The results demonstrated that the activation of NLRP3, caspase‑1 and sirtuin 1 (SIRT1), enhanced the production of inflammatory cytokines and reactive oxygen species (ROS) following TBI. Administration of resveratrol alleviated the degree of TBI, as evidenced by the reduced neuron‑specific enolase (NSE) and brain water content (WBC). Resveratrol pretreatment also inhibited the activation of NLRP3 and caspase‑1, and reduced the production of inflammatory cytokines and ROS. In addition, resveratrol further promoted SIRT1 activation. Furthermore, the suppressing effect of resveratrol on the NLRP3 inflammasome and ROS was blocked by the SIRT1 inhibitor, sirtinol. The results revealed that the activation of the NLRP3 inflammasome and the subsequent inflammatory responses in the cerebral cortex were involved in the process of TBI. Resveratrol may attenuate the inflammatory response and relieve TBI by reducing ROS production and inhibiting NLRP3 activation. The effect of resveratrol on NLRP3 inflammasome and ROS may also be SIRT1 dependent.

Prostaglandin production by melanocytic cells and the effect of alpha-melanocyte stimulating hormone.

PubMed

Nicolaou, Anna; Estdale, Sian E; Tsatmali, Marina; Herrero, Daniel Pascual; Thody, Anthony J

2004-07-16

Prostaglandins are potent mediators of the inflammatory response and are also involved in cancer development. In this study, we show that human melanocytes and FM55 melanoma cells express cyclooxygenase-1 and -2 (COX-1 and -2) and thus have the capability to produce prostaglandins. The FM55 cells produced predominantly PGE2 and PGF2alpha, whereas the HaCaT keratinocyte cell line produced mainly PGE2. The anti-inflammatory peptide, alpha-melanocyte stimulating hormone (alpha-MSH), reduced prostaglandin production in FM55 and HaCaT cells and reversed the effect of the pro-inflammatory cytokine TNF-alpha in the former. These results indicate that melanocytes produce prostaglandins and that alpha-MSH, by inhibiting this response, may play an important role in regulating inflammatory responses in the skin.

Asian Dust Particles Induce Macrophage Inflammatory Responses via Mitogen-Activated Protein Kinase Activation and Reactive Oxygen Species Production

PubMed Central

Higashisaka, Kazuma; Fujimura, Maho; Taira, Mayu; Yoshida, Tokuyuki; Tsunoda, Shin-ichi; Baba, Takashi; Yamaguchi, Nobuyasu; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Nasu, Masao; Tsutsumi, Yasuo

2014-01-01

Asian dust is a springtime meteorological phenomenon that originates in the deserts of China and Mongolia. The dust is carried by prevailing winds across East Asia where it causes serious health problems. Most of the information available on the impact of Asian dust on human health is based on epidemiological investigations, so from a biological standpoint little is known of its effects. To clarify the effects of Asian dust on human health, it is essential to assess inflammatory responses to the dust and to evaluate the involvement of these responses in the pathogenesis or aggravation of disease. Here, we investigated the induction of inflammatory responses by Asian dust particles in macrophages. Treatment with Asian dust particles induced greater production of inflammatory cytokines interleukin-6 and tumor necrosis factor-α (TNF-α) compared with treatment with soil dust. Furthermore, a soil dust sample containing only particles ≤10 μm in diameter provoked a greater inflammatory response than soil dust samples containing particles >10 μm. In addition, Asian dust particles-induced TNF-α production was dependent on endocytosis, the production of reactive oxygen species, and the activation of nuclear factor-κB and mitogen-activated protein kinases. Together, these results suggest that Asian dust particles induce inflammatory disease through the activation of macrophages. PMID:24987712

Dual Functions of the Trans-2-Enoyl-CoA Reductase TER in the Sphingosine 1-Phosphate Metabolic Pathway and in Fatty Acid Elongation*

PubMed Central

Wakashima, Takeshi; Abe, Kensuke; Kihara, Akio

2014-01-01

The sphingolipid metabolite sphingosine 1-phosphate (S1P) functions as a lipid mediator and as a key intermediate of the sole sphingolipid to glycerophospholipid metabolic pathway (S1P metabolic pathway). In this pathway, S1P is converted to palmitoyl-CoA through 4 reactions, then incorporated mainly into glycerophospholipids. Although most of the genes responsible for the S1P metabolic pathway have been identified, the gene encoding the trans-2-enoyl-CoA reductase, responsible for the saturation step (conversion of trans-2-hexadecenoyl-CoA to palmitoyl-CoA) remains unidentified. In the present study, we show that TER is the missing gene in mammals using analyses involving yeast cells, deleting the TER homolog TSC13, and TER-knockdown HeLa cells. TER is known to be involved in the production of very long-chain fatty acids (VLCFAs). A significant proportion of the saturated and monounsaturated VLCFAs are used for sphingolipid synthesis. Therefore, TER is involved in both the production of VLCFAs used in the fatty acid moiety of sphingolipids as well as in the degradation of the sphingosine moiety of sphingolipids via S1P. PMID:25049234

Impact of Animated Spokes-Characters in Print Direct-to-Consumer Prescription Drug Advertising: An Elaboration Likelihood Model Approach.

PubMed

Bhutada, Nilesh S; Rollins, Brent L; Perri, Matthew

2017-04-01

A randomized, posttest-only online survey study of adult U.S. consumers determined the advertising effectiveness (attitude toward ad, brand, company, spokes-characters, attention paid to the ad, drug inquiry intention, and perceived product risk) of animated spokes-characters in print direct-to-consumer (DTC) advertising of prescription drugs and the moderating effects of consumers' involvement. Consumers' responses (n = 490) were recorded for animated versus nonanimated (human) spokes-characters in a fictitious DTC ad. Guided by the elaboration likelihood model, data were analyzed using a 2 (spokes-character type: animated/human) × 2 (involvement: high/low) factorial multivariate analysis of covariance (MANCOVA). The MANCOVA indicated significant main effects of spokes-character type and involvement on the dependent variables after controlling for covariate effects. Of the several ad effectiveness variables, consumers only differed on their attitude toward the spokes-characters between the two spokes-character types (specifically, more favorable attitudes toward the human spokes-character). Apart from perceived product risk, high-involvement consumers reacted more favorably to the remaining ad effectiveness variables compared to the low-involvement consumers, and exhibited significantly stronger drug inquiry intentions during their next doctor visit. Further, the moderating effect of consumers' involvement was not observed (nonsignificant interaction effect between spokes-character type and involvement).

Market penetration of biodiesel and ethanol

NASA Astrophysics Data System (ADS)

Szulczyk, Kenneth Ray

This dissertation examines the influence that economic and technological factors have on the penetration of biodiesel and ethanol into the transportation fuels market. This dissertation focuses on four aspects. The first involves the influence of fossil fuel prices, because biofuels are substitutes and have to compete in price. The second involves biofuel manufacturing technology, principally the feedstock-to-biofuel conversion rates, and the biofuel manufacturing costs. The third involves prices for greenhouse gas offsets. The fourth involves the agricultural commodity markets for feedstocks, and biofuel byproducts. This dissertation uses the Forest and Agricultural Sector Optimization Model-Greenhouse Gas (FASOM-GHG) to quantitatively examine these issues and calculates equilibrium prices and quantities, given market interactions, fossil fuel prices, carbon dioxide equivalent prices, government biofuel subsidies, technological improvement, and crop yield gains. The results indicate that for the ranges studied, gasoline prices have a major impact on aggregate ethanol production but only at low prices. At higher prices, one runs into a capacity constraint that limits expansion on the capacity of ethanol production. Aggregate biodiesel production is highly responsive to gasoline prices and increases over time. (Diesel fuel price is proportional to the gasoline price). Carbon dioxide equivalent prices expand the biodiesel industry, but have no impact on ethanol aggregate production when gasoline prices are high again because of refinery capacity expansion. Improvement of crop yields shows a similar pattern, expanding ethanol production when the gasoline price is low and expanding biodiesel. Technological improvement, where biorefinery production costs decrease over time, had minimal impact on aggregate ethanol and biodiesel production. Finally, U.S. government subsidies have a large expansionary impact on aggregate biodiesel production. Finally, U.S. government subsidies have a large expansionary impact on aggregate biodiesel production, but only expand the ethanol industry at low gasoline prices. All of these factors increase agricultural welfare with most expanding producer surplus and mixed effects on consumers.

Structural brain aging and speech production: a surface-based brain morphometry study.

PubMed

Tremblay, Pascale; Deschamps, Isabelle

2016-07-01

While there has been a growing number of studies examining the neurofunctional correlates of speech production over the past decade, the neurostructural correlates of this immensely important human behaviour remain less well understood, despite the fact that previous studies have established links between brain structure and behaviour, including speech and language. In the present study, we thus examined, for the first time, the relationship between surface-based cortical thickness (CT) and three different behavioural indexes of sublexical speech production: response duration, reaction times and articulatory accuracy, in healthy young and older adults during the production of simple and complex meaningless sequences of syllables (e.g., /pa-pa-pa/ vs. /pa-ta-ka/). The results show that each behavioural speech measure was sensitive to the complexity of the sequences, as indicated by slower reaction times, longer response durations and decreased articulatory accuracy in both groups for the complex sequences. Older adults produced longer speech responses, particularly during the production of complex sequence. Unique age-independent and age-dependent relationships between brain structure and each of these behavioural measures were found in several cortical and subcortical regions known for their involvement in speech production, including the bilateral anterior insula, the left primary motor area, the rostral supramarginal gyrus, the right inferior frontal sulcus, the bilateral putamen and caudate, and in some region less typically associated with speech production, such as the posterior cingulate cortex.

Effect of Aerva lanata on cell-mediated immune responses and cytotoxic T-lymphocyte generation in normal and tumor-bearing mice.

PubMed

Siveen, K S; Kuttan, Girija

2012-01-01

Cell-mediated immunity offers protection against virus-infected cells and tumor cells, involves activation of natural killer (NK) cells, production of antigen-specific cytotoxic T-lymphocytes, and release of various cytokines in response to an antigen. Administration of an ethanolic extract of Aerva lanata was found to stimulate cell-mediated immunological responses in normal and tumor-bearing BALB/c mice. A significant enhancement in NK cell activity in both normal and tumor-bearing hosts was observed after administration of A. lanata. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement-mediated cytotoxicity (ACC) were significantly enhanced as well in both sets of treated hosts. In addition, in vivo production of IL-2 and IFNg were each significantly enhanced by extract treatment. The stimulatory effect of A. lanata on cytotoxic T-lymphocyte (CTL) production was determined by Winn's neutralization assay using CTL-sensitive EL4 thymoma cells. A. lanata treatment caused a significant increase in CTL production in both in vivo and in vitro models, in each case as indicated by a significant increase in the life-spans of tumor-injected mice. Taken together, all of these results in the murine model indicate that administration of an ethanolic extract of A. lanata could enhance the cell-mediated anti-tumor response.

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

PubMed

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

2015-01-01

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

The role of cytokines in immune changes induced by spaceflight

NASA Technical Reports Server (NTRS)

Sonnenfeld, G.; Miller, E. S.

1993-01-01

It has become apparent that spaceflight alters many immune responses. Among the regulatory components of the immune response that have been shown to be affected by spaceflight is the cytokine network. Spaceflight, as well as model systems of spaceflight, have been shown to affect the production and action of various cytokines including interferons, interleukins, colony stimulating factors, and tumor necrosis factors. These changes have been shown not to involve a general shutdown of the cytokine network but, rather, to involve selective alterations of specific cytokine functions by spaceflight. The full breadth of changes in cytokines induced by spaceflight, as well as mechanisms, duration, adaptation, reversibility, and significance to resistance to infection and neoplastic diseases, remains to be established.

Induced antiviral innate immunity in Drosophila.

PubMed

Lamiable, Olivier; Imler, Jean-Luc

2014-08-01

Immunity to viral infections in the model organism Drosophila melanogaster involves both RNA interference and additional induced responses. The latter include not only cellular mechanisms such as programmed cell death and autophagy, but also the induction of a large set of genes, some of which contribute to the control of viral replication and resistance to infection. This induced response to infection is complex and involves both virus-specific and cell-type specific mechanisms. We review here recent developments, from the sensing of viral infection to the induction of signaling pathways and production of antiviral effector molecules. Our current understanding, although still partial, validates the Drosophila model of antiviral induced immunity for insect pests and disease vectors, as well as for mammals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dual-seq transcriptomics reveals the battle for iron during Pseudomonas aeruginosa acute murine pneumonia

PubMed Central

Damron, F. Heath; Oglesby-Sherrouse, Amanda G.; Wilks, Angela; Barbier, Mariette

2016-01-01

Determining bacterial gene expression during infection is fundamental to understand pathogenesis. In this study, we used dual RNA-seq to simultaneously measure P. aeruginosa and the murine host’s gene expression and response to respiratory infection. Bacterial genes encoding products involved in metabolism and virulence were differentially expressed during infection and the type III and VI secretion systems were highly expressed in vivo. Strikingly, heme acquisition, ferric-enterobactin transport, and pyoverdine biosynthesis genes were found to be significantly up-regulated during infection. In the mouse, we profiled the acute immune response to P. aeruginosa and identified the pro-inflammatory cytokines involved in acute response to the bacterium in the lung. Additionally, we also identified numerous host iron sequestration systems upregulated during infection. Overall, this work sheds light on how P. aeruginosa triggers a pro-inflammatory response and competes for iron with the host during infection, as iron is one of the central elements for which both pathogen and host fight during acute pneumonia. PMID:27982111

Plant Perception and Short-Term Responses to Phytophagous Insects and Mites.

PubMed

Santamaria, M Estrella; Arnaiz, Ana; Gonzalez-Melendi, Pablo; Martinez, Manuel; Diaz, Isabel

2018-05-03

Plant⁻pest relationships involve complex processes encompassing a network of molecules, signals, and regulators for overcoming defenses they develop against each other. Phytophagous arthropods identify plants mainly as a source of food. In turn, plants develop a variety of strategies to avoid damage and survive. The success of plant defenses depends on rapid and specific recognition of the phytophagous threat. Subsequently, plants trigger a cascade of short-term responses that eventually result in the production of a wide range of compounds with defense properties. This review deals with the main features involved in the interaction between plants and phytophagous insects and acari, focusing on early responses from the plant side. A general landscape of the diverse strategies employed by plants within the first hours after pest perception to block the capability of phytophagous insects to develop mechanisms of resistance is presented, with the potential of providing alternatives for pest control.

Effect of 13q deletion on IL-6 production in patients with multiple myeloma: a hypothesis may hold true.

PubMed

Neemat, Kassem; Rania, Khalifa; Tarek, Mohamed; Hamdy, Abdel Azim

2014-01-01

Numerous studies have shown a correlation between 13q deletion and poor prognosis in multiple myeloma (MM), but the mechanisms are not fully understood. Earlier studies suggest that this lesion involves large segments or the entire long arm involving the retinoblastoma (Rb) gene. In myeloma, Rb gene is believed to down regulate interleukin-6 (IL-6) which plays a central role in the pathogenesis of MM. Therefore, it has been hypothesized that loss of the Rb gene might be associated with very high expression of IL-6 and subsequent bad prognosis. Hence this study evaluates IL-6 production in MM patients with and without 13q deletions and assesses their response to conventional and new therapeutic regimens. Forty MM patients and 20 matched controls were included in this study. Interphase fluorescence in situ hybridization (FISH) analysis was performed using LSI 13q14-specific probe. Serum levels of IL-6 were determined by ELISA. All patients received conventional chemotherapy. Refractory patients received other therapeutic regimens of Thalidomide or Bortezomib. Significant increase (p < 0.001) of IL-6 production was recorded in patients with a 13q deletion compared to patients with normal chromosome 13q status. These patients were also refractory to conventional chemotherapy but showed striking response to Thalidomide or Bortezomib. This study suggests that 13q deletions are associated with increased production of IL-6 in MM and this could be a possible cause of the associated bad prognosis. In addition, the results also show the potential to improve responses in patients with refractory MM with the introduction of novel therapies.

Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

PubMed Central

Elias, Rosa Maria; Correa-Costa, Matheus; Barreto, Claudiene Rodrigues; Silva, Reinaldo Correia; Hayashida, Caroline Y.; Castoldi, Ângela; Gonçalves, Giselle Martins; Braga, Tarcio Teodoro; Barboza, Renato; Rios, Francisco José; Keller, Alexandre Castro; Cenedeze, Marcos Antonio; Hyane, Meire Ioshie; D'Império-Lima, Maria Regina; Figueiredo-Neto, Antônio Martins; Reis, Marlene Antônia; Marinho, Cláudio Romero Farias; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

2012-01-01

Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA. PMID:22952850

Genotypic variation in biomass allocation in response to field drought has a greater affect on yield than gas exchange or phenology.

PubMed

Edwards, Christine E; Ewers, Brent E; Weinig, Cynthia

2016-08-24

Plant performance in agricultural and natural settings varies with moisture availability, and understanding the range of potential drought responses and the underlying genetic architecture is important for understanding how plants will respond to both natural and artificial selection in various water regimes. Here, we raised genotypes of Brassica rapa under well-watered and drought treatments in the field. Our primary goal was to understand the genetic architecture and yield effects of different drought-escape and dehydration-avoidance strategies. Drought treatments reduced soil moisture by 62 % of field capacity. Drought decreased biomass accumulation and fruit production by as much as 48 %, whereas instantaneous water-use efficiency and root:shoot ratio increased. Genotypes differed in the mean value of all traits and in the sensitivity of biomass accumulation, root:shoot ratio, and fruit production to drought. Bivariate correlations involving gas-exchange and phenology were largely constant across environments, whereas those involving root:shoot varied across treatments. Although root:shoot was typically unrelated to gas-exchange or yield under well-watered conditions, genotypes with low to moderate increases in root:shoot allocation in response to drought survived the growing season, maintained maximum photosynthesis levels, and produced more fruit than genotypes with the greatest root allocation under drought. QTL for gas-exchange and yield components (total biomass or fruit production) had common effects across environments while those for root:shoot were often environment-specific. Increases in root allocation beyond those needed to survive and maintain favorable water relations came at the cost of fruit production. The environment-specific effects of root:shoot ratio on yield and the differential expression of QTL for this trait across water regimes have important implications for efforts to improve crops for drought resistance.

The in Vitro Antigenicity of Plasmodium vivax Rhoptry Neck Protein 2 (PvRON2) B- and T-Epitopes Selected by HLA-DRB1 Binding Profile

PubMed Central

López, Carolina; Yepes-Pérez, Yoelis; Díaz-Arévalo, Diana; Patarroyo, Manuel E.; Patarroyo, Manuel A.

2018-01-01

Malaria caused by Plasmodium vivax is a neglected disease which is responsible for the highest morbidity in both Americas and Asia. Despite continuous public health efforts to prevent malarial infection, an effective antimalarial vaccine is still urgently needed. P. vivax vaccine development involves analyzing naturally-infected patients' immune response to the specific proteins involved in red blood cell invasion. The P. vivax rhoptry neck protein 2 (PvRON2) is a highly conserved protein which is expressed in late schizont rhoptries; it interacts directly with AMA-1 and might be involved in moving-junction formation. Bioinformatics approaches were used here to select B- and T-cell epitopes. Eleven high-affinity binding peptides were selected using the NetMHCIIpan-3.0 in silico prediction tool; their in vitro binding to HLA-DRB1*0401, HLA-DRB1*0701, HLA-DRB1*1101 or HLA-DRB1*1302 was experimentally assessed. Four peptides (39152 (HLA-DRB1*04 and 11), 39047 (HLA-DRB1*07), 39154 (HLADRB1*13) and universal peptide 39153) evoked a naturally-acquired T-cell immune response in P. vivax-exposed individuals from two endemic areas in Colombia. All four peptides had an SI greater than 2 in proliferation assays; however, only peptides 39154 and 39153 had significant differences compared to the control group. Peptide 39047 was able to significantly stimulate TNF and IL-10 production while 39154 stimulated TNF production. Allele-specific peptides (but not the universal one) were able to stimulate IL-6 production; however, none induced IFN-γ production. The Bepipred 1.0 tool was used for selecting four B-cell epitopes in silico regarding humoral response. Peptide 39041 was the only one recognized by P. vivax-exposed individuals' sera and had significant differences concerning IgG subclasses; an IgG2 > IgG4 profile was observed for this peptide, agreeing with a protection-inducing role against P. falciparum and P. vivax as previously described for antigens such as RESA and MSP2. The bioinformatics results and in vitro evaluation reported here highlighted two T-cell epitopes (39047 and 39154) being recognized by memory cells and a B-cell epitope (39041) identified by P. vivax-exposed individuals' sera which could be used as potential candidates when designing a subunit-based vaccine. PMID:29868512

Neisseria meningitidis elicits a pro-inflammatory response involving IκBζ in a human blood-cerebrospinal fluid barrier model.

PubMed

Borkowski, Julia; Li, Li; Steinmann, Ulrike; Quednau, Natascha; Stump-Guthier, Carolin; Weiss, Christel; Findeisen, Peter; Gretz, Norbert; Ishikawa, Hiroshi; Tenenbaum, Tobias; Schroten, Horst; Schwerk, Christian

2014-09-13

The human-specific, Gram-negative bacterium Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis worldwide. The blood-cerebrospinal fluid barrier (BCSFB), which is constituted by the epithelial cells of the choroid plexus (CP), has been suggested as one of the potential entry sites of Nm into the CSF and can contribute to the inflammatory response during infectious diseases of the brain. Toll-like receptors (TLRs) are involved in mediating signal transduction caused by the pathogens. Using a recently established in vitro model of the human BCSFB based on human malignant CP papilloma (HIBCPP) cells we investigated the cellular response of HIBCPP cells challenged with the meningitis-causing Nm strain, MC58, employing transcriptome and RT-PCR analysis, cytokine bead array, and enzyme-linked immunosorbent assay (ELISA). In comparison, we analyzed the answer to the closely related unencapsulated carrier isolate Nm α14. The presence of TLRs in HIBCPP and their role during signal transduction caused by Nm was studied by RT-PCR and the use of specific agonists and mutant bacteria. We observed a stronger transcriptional response after infection with strain MC58, in particular with its capsule-deficient mutant MC58siaD-, which correlated with bacterial invasion levels. Expression evaluation and Gene Set Enrichment Analysis pointed to a NFκB-mediated pro-inflammatory immune response involving up-regulation of the transcription factor IκBζ. Infected cells secreted significant levels of pro-inflammatory chemokines and cytokines, including, among others, IL8, CXCL1-3, and the IκBζ target gene product IL6. The expression profile of pattern recognition receptors in HIBCPP cells and the response to specific agonists indicates that TLR2/TLR6, rather than TLR4 or TLR2/TLR1, is involved in the cellular reaction following Nm infection. Our data show that Nm can initiate a pro-inflammatory response in human CP epithelial cells probably involving TLR2/TLR6 signaling and the transcriptional regulator IκBζ.

Oxysterol, 5α-cholestan-3-one, modulates a contractile response to β2-adrenoceptor stimulation in the mouse atria: Involvement of NO signaling.

PubMed

Sytchev, Vaycheslav I; Odnoshivkina, Yulia G; Ursan, Roman V; Petrov, Alexey M

2017-11-01

Atrial β2-adrenoceptors provide an important mechanism for regulation of cardiac function and changes in their downstream signaling are involved in processes underlying heart disorders. We have investigated the mechanism by which the cholesterol metabolite 5α-cholestan-3-one (5ɑCh3) modulates inotropic effect of β2-adrenoceptor agonist fenoterol. Atria from mice were electrically stimulated and changes in contraction amplitude in response to fenoterol were studied in 5ɑCh3-pretreated samples. Intracellular Ca 2+ and NO levels were estimated using fluorescent dyes Fluo-4 and DAF-FM, respectively. By itself 5αCh3 that appears in the circulation under some pathological conditions had a negligible influence on contraction, Ca 2+ -transient and NO production. However, pretreatment with 5αCh3 markedly attenuated the positive inotropic effect of fenoterol which was accompanied by an increase in the NO synthesis. Unexpectedly, the oxysterol also augmented an enhancement of Ca 2+ -transient amplitude in response to fenoterol. Under conditions of a pharmacological inhibition of G i -protein/Akt/NO synthase/protein kinase G signaling, 5αCh3 augmented the inotropic effect of fenoterol. Herein, Akt antagonist suppressed the increase in NO production, while inhibition of NO synthesis did not modify the increased amplitude of the Ca 2+ -transient. Along similar lines, enrichment of plasma membranes with cholesterol reduced the stimulatory effect of 5αCh3 on β2-adrenoceptor-evoked NO production, but not on the Ca2+-transient amplitude, leading to an elevation of the positive inotropic response to fenoterol. These data suggest that 5ɑCh3 potentiates the effect of pharmacological β2-adrenoceptor activation on both NO production and Ca 2+ transient via independent mechanisms, thereby affecting the positive inotropy. Copyright © 2017 Elsevier Inc. All rights reserved.

Modeling spatial patterns of limits to production of deposit-feeders and ectothermic predators in the northern Bering Sea

NASA Astrophysics Data System (ADS)

Lovvorn, James R.; Jacob, Ute; North, Christopher A.; Kolts, Jason M.; Grebmeier, Jacqueline M.; Cooper, Lee W.; Cui, Xuehua

2015-03-01

Network models can help generate testable predictions and more accurate projections of food web responses to environmental change. Such models depend on predator-prey interactions throughout the network. When a predator currently consumes all of its prey's production, the prey's biomass may change substantially with loss of the predator or invasion by others. Conversely, if production of deposit-feeding prey is limited by organic matter inputs, system response may be predictable from models of primary production. For sea floor communities of shallow Arctic seas, increased temperature could lead to invasion or loss of predators, while reduced sea ice or change in wind-driven currents could alter organic matter inputs. Based on field data and models for three different sectors of the northern Bering Sea, we found a number of cases where all of a prey's production was consumed but the taxa involved varied among sectors. These differences appeared not to result from numerical responses of predators to abundance of preferred prey. Rather, they appeared driven by stochastic variations in relative biomass among taxa, due largely to abiotic conditions that affect colonization and early post-larval survival. Oscillatory tendencies of top-down versus bottom-up interactions may augment these variations. Required inputs of settling microalgae exceeded existing estimates of annual primary production by 50%; thus, assessing limits to bottom-up control depends on better corrections of satellite estimates to account for production throughout the water column. Our results suggest that in this Arctic system, stochastic abiotic conditions outweigh deterministic species interactions in food web responses to a varying environment.

Insights into the functionality of the putative residues involved in enterocin AS-48 maturation.

PubMed

Cebrián, Rubén; Maqueda, Mercedes; Neira, José Luis; Valdivia, Eva; Martínez-Bueno, Manuel; Montalbán-López, Manuel

2010-11-01

AS-48 is a 70-residue, α-helical, cationic bacteriocin produced by Enterococcus faecalis and is very singular in its circular structure and its broad antibacterial spectrum. The AS-48 preprotein consists of an N-terminal signal peptide (SP) (35 residues) followed by a proprotein moiety that undergoes posttranslational modifications to yield the mature and active circular protein. For the study of the specificity of the region of AS-48 that is responsible for maturation, three single mutants have been generated by site-directed mutagenesis in the as-48A structural gene. The substitutions were made just in the residues that are thought to constitute a recognition site for the SP cleavage enzyme (His-1, Met1) and in those involved in circularization (Met1, Trp70). Each derivative was expressed in the enterococcal JH2-2 strain containing the necessary native biosynthetic machinery for enterocin production. The importance of these derivatives in AS-48 processing has been evaluated on the basis of the production and structural characterization of the corresponding derivatives. Notably, only two of them (Trp70Ala and Met1Ala derivatives) could be purified in different forms and amounts and are characterized for their bactericidal activity and secondary structure. We could not detect any production of AS-48 in JH2-2(pAM401-81(His-1Ile)) by using the conventional chromatographic techniques, despite the high efficiency of the culture conditions applied to produce this enterocin. Our results underline the different important roles of the mutated residues in (i) the elimination of the SP, (ii) the production levels and antibacterial activity of the mature proteins, and (iii) protein circularization. Moreover, our findings suggest that His-1 is critically involved in cleavage site recognition, its substitution being responsible for the blockage of processing, thereby hampering the production of the specific protein in the cellular culture supernatant.

Response of lactate metabolism in brain glucosensing areas of rainbow trout (Oncorhynchus mykiss) to changes in glucose levels.

PubMed

Otero-Rodiño, Cristina; Librán-Pérez, Marta; Velasco, Cristina; Álvarez-Otero, Rosa; López-Patiño, Marcos A; Míguez, Jesús M; Soengas, José L

2015-12-01

There is no evidence in fish brain demonstrating the existence of changes in lactate metabolism in response to alterations in glucose levels. We induced in rainbow trout through intraperitoneal (IP) treatments, hypoglycaemic or hyperglycaemic changes to assess the response of parameters involved in lactate metabolism in glucosensing areas like hypothalamus and hindbrain. To distinguish those effects from those induced by peripheral changes in the levels of metabolites or hormones, we also carried out intracerebroventricular (ICV) treatments with 2-deoxy-D-glucose (2-DG, a non-metabolizable glucose analogue thus inducing local glucopenia) or glucose. Finally, we also incubated hypothalamus and hindbrain in vitro in the presence of increased glucose concentrations. The changes in glucose availability were in general correlated to changes in the amount of lactate in both areas. However, when we assessed in these areas the response of parameters related to lactate metabolism, the results obtained were contradictory. The increase in glucose levels did not produce in general the expected changes in those pathways with only a minor increase in their capacity of lactate production. The decrease in glucose levels was, however, more clearly related to a decreased capacity of the pathways involved in the production and use of lactate, and this was especially evident after ICV treatment with 2-DG in both areas. In conclusion, the present results while addressing the existence of changes in lactate metabolism after inducing changes in glucose levels in brain glucosensing areas only partially support the possible existence of an astrocyte-neuron lactate shuttle in hypothalamus and hindbrain of rainbow trout relating glucose availability to lactate production and use.

Cerebellar contributions to motor timing: a PET study of auditory and visual rhythm reproduction.

PubMed

Penhune, V B; Zattore, R J; Evans, A C

1998-11-01

The perception and production of temporal patterns, or rhythms, is important for both music and speech. However, the way in which the human brain achieves accurate timing of perceptual input and motor output is as yet little understood. Central control of both motor timing and perceptual timing across modalities has been linked to both the cerebellum and the basal ganglia (BG). The present study was designed to test the hypothesized central control of temporal processing and to examine the roles of the cerebellum, BG, and sensory association areas. In this positron emission tomography (PET) activation paradigm, subjects reproduced rhythms of increasing temporal complexity that were presented separately in the auditory and visual modalities. The results provide support for a supramodal contribution of the lateral cerebellar cortex and cerebellar vermis to the production of a timed motor response, particularly when it is complex and/or novel. The results also give partial support to the involvement of BG structures in motor timing, although this may be more directly related to implementation of the motor response than to timing per se. Finally, sensory association areas and the ventrolateral frontal cortex were found to be involved in modality-specific encoding and retrieval of the temporal stimuli. Taken together, these results point to the participation of a number of neural structures in the production of a timed motor response from an external stimulus. The role of the cerebellum in timing is conceptualized not as a clock or counter but simply as the structure that provides the necessary circuitry for the sensory system to extract temporal information and for the motor system to learn to produce a precisely timed response.

Metabolic response against sulfur-containing heterocyclic compounds by the lignin-degrading basidiomycete Coriolus versicolor.

PubMed

Ichinose, H; Nakamizo, M; Wariishi, H; Tanaka, H

2002-03-01

The fungal conversions of sulfur-containing heterocyclic compounds were investigated using the lignin-degrading basidiomycete Coriolus versicolor. The fungus metabolized a series of sulfur compounds--25 structurally related thiophene derivatives--via several different pathways. Under primary metabolic conditions, C. versicolor utilized thiophenes, such as 2-hydroxymethyl-, 2-formyl-, and 2-carboxyl-thiophenes, as a nutrient sulfur source for growth; thus, the fungus degraded these compounds more effectively in a non-sulfur-containing medium than in conventional medium. The product analysis revealed that several redox reactions, decarboxylation reactions, and C-S cleavage reactions were involved in the fungal conversion of non-aromatic thiophenes. On the other hand, benzothiophene (BT) and dibenzothiophene (DBT) skeletons were converted to water-soluble products. All the products and metabolic intermediates were more hydrophilic than the starting substrates. These metabolic actions seemed to be a chemical stress response against exogenously added xenobiotics. These metabolic reactions were optimized under ligninolytic conditions, also suggesting the occurrence of a fungal xenobiotic response. Furthermore, the fungus converted a series of BTs and DBTs via several different pathways, which seemed to be controlled by the chemical structure of the substrates. DBT, 4-methylDBT, 4, 6-dimethylDBT, 2-methylBT, and 7-methylBT were immediately oxidized to their S-oxides. BTs and DBTs with the hydroxymethyl substituent were converted to their xylosides without S-oxidation. Those with carboxyl and formyl substituents were reduced to form a hydroxymethyl group, then xylosidated. These observations strongly suggested the involvement of a fungal substrate-recognition and metabolic response mechanism in the metabolism of sulfur-containing heterocyclic compounds by C. versicolor.

Creative tensions: mutual responsiveness adapted to private sector research and development.

PubMed

Sonck, Matti; Asveld, Lotte; Landeweerd, Laurens; Osseweijer, Patricia

2017-09-07

The concept of mutual responsiveness is currently based on little empirical data in the literature of Responsible Research and Innovation (RRI). This paper explores RRI's idea of mutual responsiveness in the light of recent RRI case studies on private sector research and development (R&D). In RRI, responsible innovation is understood as a joint endeavour of innovators and societal stakeholders, who become mutually responsive to each other in defining the 'right impacts' of the innovation in society, and in steering the innovation towards realising those impacts. Yet, the case studies identified several reasons for why the idea of mutual responsiveness does not always appear feasible or desirable in actual R&D situations. Inspired by the discrepancies between theory and practice, we suggest three further elaborations for the concept of responsiveness in RRI. Process-responsiveness is suggested for identifying situations that require stakeholder involvement specifically during R&D. Product-responsiveness is suggested for mobilising the potential of innovation products to be adaptable according to diverse stakeholder needs. Presponsiveness is suggested as responsiveness towards stakeholders that are not (yet) reachable at a given time of R&D. Our aim is to contribute to a more tangible understanding of responsiveness in RRI, and suggest directions for further analysis in upcoming RRI case studies.

Transcriptomic and metabolomic analyses identify a role for chlorophyll catabolism and phytoalexin during Medicago nonhost resistance against Asian soybean rust.

PubMed

Ishiga, Yasuhiro; Uppalapati, Srinivasa Rao; Gill, Upinder S; Huhman, David; Tang, Yuhong; Mysore, Kirankumar S

2015-08-12

Asian soybean rust (ASR) caused by Phakopsora pachyrhizi is a devastating foliar disease affecting soybean production worldwide. Understanding nonhost resistance against ASR may provide an avenue to engineer soybean to confer durable resistance against ASR. We characterized a Medicago truncatula-ASR pathosystem to study molecular mechanisms of nonhost resistance. Although urediniospores formed appressoria and penetrated into epidermal cells of M. truncatula, P. pachyrhizi failed to sporulate. Transcriptomic analysis revealed the induction of phenylpropanoid, flavonoid and isoflavonoid metabolic pathway genes involved in the production of phytoalexin medicarpin in M. truncatula upon infection with P. pachyrhizi. Furthermore, genes involved in chlorophyll catabolism were induced during nonhost resistance. We further characterized one of the chlorophyll catabolism genes, Stay-green (SGR), and demonstrated that the M. truncatula sgr mutant and alfalfa SGR-RNAi lines showed hypersensitive-response-like enhanced cell death upon inoculation with P. pachyrhizi. Consistent with transcriptomic analysis, metabolomic analysis also revealed the accumulation of medicarpin and its intermediate metabolites. In vitro assay showed that medicarpin inhibited urediniospore germination and differentiation. In addition, several triterpenoid saponin glycosides accumulated in M. truncatula upon inoculation with P. pachyrhizi. In summary, using multi-omic approaches, we identified a correlation between phytoalexin production and M. truncatula defense responses against ASR.

Helicobacter pylori-induced IL-33 modulates mast cell responses, benefits bacterial growth, and contributes to gastritis.

PubMed

Lv, Yi-Pin; Teng, Yong-Sheng; Mao, Fang-Yuan; Peng, Liu-Sheng; Zhang, Jin-Yu; Cheng, Ping; Liu, Yu-Gang; Kong, Hui; Wang, Ting-Ting; Wu, Xiao-Long; Hao, Chuan-Jie; Chen, Weisan; Yang, Shi-Ming; Zhao, Yong-Liang; Han, Bin; Ma, Qiang; Zou, Quan-Ming; Zhuang, Yuan

2018-04-25

Interleukin (IL)-induced inflammatory responses are critical for the pathogenesis of Helicobacter pylori (H. pylori)-induced gastritis. IL-33 represents a recently discovered proinflammatory cytokine involved in inflammatory diseases, but its relevance to H. pylori-induced gastritis is unknown. Here, we found that gastric IL-33 mRNA and protein expression were elevated in gastric mucosa of both patients and mice infected with H. pylori, which is positively correlated with bacterial load and the degree of gastritis. IL-33 production was promoted via extracellular regulated protein kinases (ERK) signaling pathway activation by gastric epithelial cells in a cagA-dependent manner during H. pylori infection, and resulted in increased inflammation and bacteria burden within the gastric mucosa. Gastric epithelial cell-derived IL-33 promoted TNF-α production from mast cells in vitro, and IL-33 increased TNF-α production in vivo. Increased TNF-α inhibited gastric epithelial cell proliferation, conducing to the progress of H. pylori-associated gastritis and bacteria colonization. This study defined a patent regulatory networks involving H. pylori, gastric epithelial cell, IL-33, mast cell, and TNF-α, which jointly play a pathological effect within the gastric circumstances. It may be a valuable strategy to restrain this IL-33-dependent pathway in the treatment of H. pylori-associated gastritis.

Involvement of TRPV2 activation in intestinal movement through nitric oxide production in mice.

PubMed

Mihara, Hiroshi; Boudaka, Ammar; Shibasaki, Koji; Yamanaka, Akihiro; Sugiyama, Toshiro; Tominaga, Makoto

2010-12-08

Transient receptor potential channel vanilloid 2 (TRPV2) can detect various stimuli such as temperature (>52 °C), stretch, and chemicals, including 2-aminoethoxydiphenyl borate, probenecid, and lysophospholipids. Although expressed in many tissues, including sensory and motor neurons, TRPV2 expression and function in the gastrointestinal tract is poorly understood. Here, we show TRPV2 expression in the murine intestine and its involvement in intestinal function. Almost all mouse intestinal intrinsic sensory and inhibitory motor neurons, both cell bodies and nerve fibers, showed TRPV2 immunoreactivity. Several known TRPV2 activators increased cytosolic Ca²+ concentrations and evoked TRPV2-like current responses in dissociated myenteric neurons. Interestingly, mechanical stimuli activated inward currents in a strength-dependent manner, which were inhibited by a TRPV2 inhibitor tranilast. TRPV2 activation in isolated intestine inhibited spontaneous circular muscle contraction, which did not occur in the presence of the TRPV2 antagonist, tetrodotoxin or nitro oxide (NO) synthase pathway inhibitors. Also, increased intestinal NO production was observed in response to a TRPV2 agonist, and gastrointestinal transit in vivo was accelerated by TRPV2 agonists or an NO donor. In conclusion, TRPV2 may contribute to intestinal motility through NO production, and TRPV2 is a promising target for controlling intestinal movement.

Inorganic Phosphate Limitation Modulates Capsular Polysaccharide Composition in Mycobacteria.

PubMed

van de Weerd, Robert; Boot, Maikel; Maaskant, Janneke; Sparrius, Marion; Verboom, Theo; van Leeuwen, Lisanne M; Burggraaf, Maroeska J; Paauw, Nanne J; Dainese, Elisa; Manganelli, Riccardo; Bitter, Wilbert; Appelmelk, Ben J; Geurtsen, Jeroen

2016-05-27

Mycobacterium tuberculosis is protected by an unusual and highly impermeable cell envelope that is critically important for the successful colonization of the host. The outermost surface of this cell envelope is formed by capsular polysaccharides that play an important role in modulating the initial interactions once the bacillus enters the body. Although the bioenzymatic steps involved in the production of the capsular polysaccharides are emerging, information regarding the ability of the bacterium to modulate the composition of the capsule is still unknown. Here, we study the mechanisms involved in regulation of mycobacterial capsule biosynthesis using a high throughput screen for gene products involved in capsular α-glucan production. Utilizing this approach we identified a group of mutants that all carried mutations in the ATP-binding cassette phosphate transport locus pst These mutants collectively exhibited a strong overproduction of capsular polysaccharides, including α-glucan and arabinomannan, suggestive of a role for inorganic phosphate (Pi) metabolism in modulating capsular polysaccharide production. These findings were corroborated by the observation that growth under low Pi conditions as well as chemical activation of the stringent response induces capsule production in a number of mycobacterial species. This induction is, in part, dependent on σ factor E. Finally, we show that Mycobacterium marinum, a model organism for M. tuberculosis, encounters Pi stress during infection, which shows the relevance of our findings in vivo. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Deletion of genes involved in glutamate metabolism to improve poly-gamma-glutamic acid production in B. amyloliquefaciens LL3.

PubMed

Zhang, Wei; He, Yulian; Gao, Weixia; Feng, Jun; Cao, Mingfeng; Yang, Chao; Song, Cunjiang; Wang, Shufang

2015-02-01

Here, we attempted to elevate poly-gamma-glutamic acid (γ-PGA) production by modifying genes involved in glutamate metabolism in Bacillus amyloliquefaciens LL3. Products of rocR, rocG and gudB facilitate the conversion from glutamate to 2-oxoglutarate in Bacillus subtillis. The gene odhA is responsible for the synthesis of a component of the 2-oxoglutarate dehydrogenase complex that catalyzes the oxidative decarboxylation of 2-oxoglutarate to succinyl coenzyme A. In-frame deletions of these four genes were performed. In shake flask experiments the gudB/rocG double mutant presented enhanced production of γ-PGA, a 38 % increase compared with wild type. When fermented in a 5-L fermenter with pH control, the γ-PGA yield of the rocR mutant was increased to 5.83 g/L from 4.55 g/L for shake flask experiments. The gudB/rocG double mutant produced 5.68 g/L γ-PGA compared with that of 4.03 g/L for the wild type, a 40 % increase. Those results indicated the possibility of improving γ-PGA production by modifying glutamate metabolism, and identified potential genetic targets to improve γ-PGA production.

Production of ergothioneine by Methylobacterium species

PubMed Central

Alamgir, Kabir M.; Masuda, Sachiko; Fujitani, Yoshiko; Fukuda, Fumio; Tani, Akio

2015-01-01

Metabolomic analysis revealed that Methylobacterium cells accumulate a large amount of ergothioneine (EGT), which is a sulfur-containing, non-proteinogenic, antioxidative amino acid derived from histidine. EGT biosynthesis and its role in methylotrophy and physiology for plant surface-symbiotic Methylobacterium species were investigated in this study. Almost all Methylobacterium type strains can synthesize EGT. We selected one of the most productive strains (M. aquaticum strain 22A isolated from a moss), and investigated the feasibility of fermentative EGT production through optimization of the culture condition. Methanol as a carbon source served as the best substrate for production. The productivity reached up to 1000 μg/100 ml culture (1200 μg/g wet weight cells, 6.3 mg/g dry weight) in 38 days. Next, we identified the genes (egtBD) responsible for EGT synthesis, and generated a deletion mutant defective in EGT production. Compared to the wild type, the mutant showed better growth on methanol and on the plant surface as well as severe susceptibility to heat treatment and irradiation of ultraviolet (UV) and sunlight. These results suggested that EGT is not involved in methylotrophy, but is involved in their phyllospheric lifestyle fitness of the genus in natural conditions. PMID:26579093

Production of ergothioneine by Methylobacterium species.

PubMed

Alamgir, Kabir M; Masuda, Sachiko; Fujitani, Yoshiko; Fukuda, Fumio; Tani, Akio

2015-01-01

Metabolomic analysis revealed that Methylobacterium cells accumulate a large amount of ergothioneine (EGT), which is a sulfur-containing, non-proteinogenic, antioxidative amino acid derived from histidine. EGT biosynthesis and its role in methylotrophy and physiology for plant surface-symbiotic Methylobacterium species were investigated in this study. Almost all Methylobacterium type strains can synthesize EGT. We selected one of the most productive strains (M. aquaticum strain 22A isolated from a moss), and investigated the feasibility of fermentative EGT production through optimization of the culture condition. Methanol as a carbon source served as the best substrate for production. The productivity reached up to 1000 μg/100 ml culture (1200 μg/g wet weight cells, 6.3 mg/g dry weight) in 38 days. Next, we identified the genes (egtBD) responsible for EGT synthesis, and generated a deletion mutant defective in EGT production. Compared to the wild type, the mutant showed better growth on methanol and on the plant surface as well as severe susceptibility to heat treatment and irradiation of ultraviolet (UV) and sunlight. These results suggested that EGT is not involved in methylotrophy, but is involved in their phyllospheric lifestyle fitness of the genus in natural conditions.

Near Real-Time Use of Optical Remote Sensing and Synthetic Aperture Radar for Response to Central U.S. Flooding in Late April-Early May 2017

NASA Astrophysics Data System (ADS)

Bell, J. R.; Schultz, L. A.; Jones, M.; Molthan, A.; Arko, S. A.; Hogenson, K.; Meyer, F. J.

2017-12-01

In late April and early May 2017, heavy rainfall across Missouri led to extensive flooding along the Missouri and Mississippi River basins in the Central United States. Determining the extent of flooding is critical for response organizations to properly deploy personnel and other assets involved in preparedness, mitigation, response, and recovery efforts. The Federal Emergency Management Agency (FEMA) relies on geospatial flood extent data, among other data, to estimate the impacts to population and infrastructure in order to prepare and engage response activities in support of the affected states and communities. To assist FEMA in mapping flood extent in a near real-time, the NASA Earth Science Disasters Program coordinates a multi-NASA center response to provide satellite imagery and products to FEMA during major flood events to supplement their analysis tools and capabilities. Scientists at the NASA Short-term Prediction Research and Transition (SPoRT) Center at Marshall Space Flight Center, who led this particular response, have been working with the Alaska Satellite Facility (ASF) at the University of Alaska Fairbanks to provide synthetic aperture radar (SAR) imagery and derived flood products to FEMA's geospatial response team in support of flooding events. Combined, these efforts helped to provide preliminary flood mapping to FEMA from a broad constellation of remote sensors. The presentation will describe the various products available throughout the response event, post-event collaborations examining these products in comparison to additional modeling and data collection by FEMA, training needs to improve product use, and more efficient methods for data delivery. Lessons learned will highlight opportunities for future work and improvement, and guide other ongoing efforts to develop collaborations that would also support other domestic emergency response activities, such as those led by the National Guard Bureau, which assists individual state Guard units.

Examining Focused L2 Practice: From in Vitro to in Vivo

ERIC Educational Resources Information Center

Cornillie, Frederik; Van Den Noortgate, Wim; Van den Branden, Kris; Desmet, Piet

2017-01-01

Behaviour-tracking technology has been used for decades in SLA research on focused practice with an eye toward elucidating the nature of L2 automatization (e.g. DeKeyser, 1997; Robinson, 1997). This involves longitudinally capturing learners' judgments or linguistic production along with their response times in order to investigate how specific…

The Blake Interaction Model for Task Force Program Development in Vocational Education.

ERIC Educational Resources Information Center

Blake, Duane L.

The Blake Interaction Model presented in this manual is designed to eliminate three problems which usually confront a task force charged with the responsibility of program development in a conference setting: (1) how to involve simultaneously several work groups in the productive capacity developing solutions for several separate problems; (2) how…

Employee Deviance: A Response to the Perceived Quality of the Work Experience.

ERIC Educational Resources Information Center

Hollinger, Richard; Clark, John

1982-01-01

Studies of deviant behavior in the work setting have assumed that an important factor is the employee's perception of the quality of the work experience. This study shows that measures of job satisfaction are significantly related to reported involvement in both property and production deviance in the workplace. (Author/SK)

Metabolic and physiological mechanisms responsible for variation in feed efficiency

USDA-ARS?s Scientific Manuscript database

There has been an increase in the number of experiments in the past few years that explore the underlying mechanisms involved in feed efficiency of beef cattle. This is a byproduct of the need to improve feed efficiency to increase the sustainability of beef production and improve the economic situa...

An Evaluation of a Performing Arts Experiment in a Special School.

ERIC Educational Resources Information Center

Harland, John

1990-01-01

Describes an experimental project to infuse performing arts into the curriculum of a North Yorkshire residential school for emotionally and behaviorally disturbed boys, 11-16. The project involved artists in applying the Royal Opera House model, in which children take responsibility for the creation of their own musical production. (SK)

Remote sensing procurement package: A technical guide for state and local governments

NASA Technical Reports Server (NTRS)

1981-01-01

The guide provides the tools and techniques for procuring remote sensing products and services. It is written for administrators, procurement officials and line agency staff who are directly involved in identifying information needs; defining remote sensing project requirements; soliciting and evaluating contract responses and negotiating, awarding, and administering contracts.

The Logic of School Gardens: A Phenomenological Study of Teacher Rationales

ERIC Educational Resources Information Center

Jorgenson, Simon

2013-01-01

Despite the importance of teachers to the school garden movement, we still know very little about what drives particular teachers to incorporate a school garden into their pedagogy. In response, this article reports the findings of a study designed to investigate the internal processes and products involved in rationalising and sustaining…

Uncoupling protein expression in skeletal muscle and adipose tissue in response to in vivo porcine somatotropin treatment

USDA-ARS?s Scientific Manuscript database

The uncoupling proteins are thought to be involved in waste heat production, reducing the energy efficiency of growth in animals. Previous studies have detected their presence in swine and their regulation by the endocrine system. This study attempted to determine whether the uncoupling proteins 2...

Deciphering early events involved in hyperosmotic stress-induced programmed cell death in tobacco BY-2 cells

PubMed Central

Monetti, Emanuela; Kadono, Takashi; Bouteau, François

2014-01-01

Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on early responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca2+ concentration ([Ca2+]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·–) generation by NADPH-oxidase. In the case of NaCl, an early influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·– generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared early responses, such as [Ca2+]cyt increase and singlet oxygen production, do not seem to be involved in PCD. PMID:24420571

(De)constructing literacy: Education inequalities and the production of space in San Diego, California

NASA Astrophysics Data System (ADS)

Tangeman, Andrew Gerrit

Since its inception, the No Child Left Behind Act of 2001 (NCLB) and recent additions to the U.S. Elementary and Secondary Education Act (ESEA) have elicited a broad swath of responses from the educational community. These responses include critical discussions of how standardized testing requirements proliferate a "teach for the test" mentality that transforms how reading, writing, and mathematics are taught in public schools. This thesis focused specifically on "literacy" in relation to the policies that challenge its status as a subjective form of communication, knowledge sharing, and story-telling. Embedded within the term "literacy" are sets of socially-constructed dualisms such as "good school" vs. "bad school," "literate" vs. "illiterate," and "reader" vs. "test-taker" that are propagated under education reform. Investigating these dualisms involved a mixed methods approach, which included the use of critical theory, geovisualization, and geographic analysis. The resulting data allows for a comprehensive look into the economic, political, social, and cultural forces involved in the production of literate space(s) in San Diego, California.

Identification and expression pattern analysis of BoMYB51 involved in indolic glucosinolate biosynthesis from broccoli (Brassica oleracea var. italica).

PubMed

Yu, Qingyue; Hao, Guodong; Zhou, Jianxin; Wang, Jingying; Evivie, Ejiroghene Ruona; Li, Jing

2018-06-22

Glucosinolates are a class of amino acid-derived specialized metabolites characteristic of the Brassicales order. Trp derived indolic glucosinolates are essential for the effective plant defense responses to a wide range of pathogens and herbivores. In Arabidopsis, MYB51 is the key transcription factor positively regulates indolic glucosinolate production by activating certain biosynthetic genes. In this study, we report the isolation and identification of a MYB51 from broccoli designated as BoMYB51. Overexpression of BoMYB51 in Arabidopsis increased indolic glucosinolate production by upregulating biosynthetic genes and resulted in enhanced flagellin22 (Flg22) induced callose deposition. The spatial expression pattern and responsive expression of BoMYB51 to several hormones and stress treatments were investigated by expressing the β-glucuronidase (GUS) reporter gene driven by BoMYB51 promotor in Arabidopsis and quantitative real-time PCR analysis in broccoli. Our study provides information on molecular characteristics of BoMYB51 and possible physiological process BoMYB51 may involve. Copyright © 2018 Elsevier Inc. All rights reserved.

Physiological, Biochemical, and Molecular Mechanisms of Heat Stress Tolerance in Plants

PubMed Central

Hasanuzzaman, Mirza; Nahar, Kamrun; Alam, Md. Mahabub; Roychowdhury, Rajib; Fujita, Masayuki

2013-01-01

High temperature (HT) stress is a major environmental stress that limits plant growth, metabolism, and productivity worldwide. Plant growth and development involve numerous biochemical reactions that are sensitive to temperature. Plant responses to HT vary with the degree and duration of HT and the plant type. HT is now a major concern for crop production and approaches for sustaining high yields of crop plants under HT stress are important agricultural goals. Plants possess a number of adaptive, avoidance, or acclimation mechanisms to cope with HT situations. In addition, major tolerance mechanisms that employ ion transporters, proteins, osmoprotectants, antioxidants, and other factors involved in signaling cascades and transcriptional control are activated to offset stress-induced biochemical and physiological alterations. Plant survival under HT stress depends on the ability to perceive the HT stimulus, generate and transmit the signal, and initiate appropriate physiological and biochemical changes. HT-induced gene expression and metabolite synthesis also substantially improve tolerance. The physiological and biochemical responses to heat stress are active research areas, and the molecular approaches are being adopted for developing HT tolerance in plants. This article reviews the recent findings on responses, adaptation, and tolerance to HT at the cellular, organellar, and whole plant levels and describes various approaches being taken to enhance thermotolerance in plants. PMID:23644891

Role of Silicon on Plant–Pathogen Interactions

PubMed Central

Wang, Min; Gao, Limin; Dong, Suyue; Sun, Yuming; Shen, Qirong; Guo, Shiwei

2017-01-01

Although silicon (Si) is not recognized as an essential element for general higher plants, it has beneficial effects on the growth and production of a wide range of plant species. Si is known to effectively mitigate various environmental stresses and enhance plant resistance against both fungal and bacterial pathogens. In this review, the effects of Si on plant–pathogen interactions are analyzed, mainly on physical, biochemical, and molecular aspects. In most cases, the Si-induced biochemical/molecular resistance during plant–pathogen interactions were dominated as joint resistance, involving activating defense-related enzymes activates, stimulating antimicrobial compound production, regulating the complex network of signal pathways, and activating of the expression of defense-related genes. The most previous studies described an independent process, however, the whole plant resistances were rarely considered, especially the interaction of different process in higher plants. Si can act as a modulator influencing plant defense responses and interacting with key components of plant stress signaling systems leading to induced resistance. Priming of plant defense responses, alterations in phytohormone homeostasis, and networking by defense signaling components are all potential mechanisms involved in Si-triggered resistance responses. This review summarizes the roles of Si in plant–microbe interactions, evaluates the potential for improving plant resistance by modifying Si fertilizer inputs, and highlights future research concerning the role of Si in agriculture. PMID:28529517

Song and speech: brain regions involved with perception and covert production.

PubMed

Callan, Daniel E; Tsytsarev, Vassiliy; Hanakawa, Takashi; Callan, Akiko M; Katsuhara, Maya; Fukuyama, Hidenao; Turner, Robert

2006-07-01

This 3-T fMRI study investigates brain regions similarly and differentially involved with listening and covert production of singing relative to speech. Given the greater use of auditory-motor self-monitoring and imagery with respect to consonance in singing, brain regions involved with these processes are predicted to be differentially active for singing more than for speech. The stimuli consisted of six Japanese songs. A block design was employed in which the tasks for the subject were to listen passively to singing of the song lyrics, passively listen to speaking of the song lyrics, covertly sing the song lyrics visually presented, covertly speak the song lyrics visually presented, and to rest. The conjunction of passive listening and covert production tasks used in this study allow for general neural processes underlying both perception and production to be discerned that are not exclusively a result of stimulus induced auditory processing nor to low level articulatory motor control. Brain regions involved with both perception and production for singing as well as speech were found to include the left planum temporale/superior temporal parietal region, as well as left and right premotor cortex, lateral aspect of the VI lobule of posterior cerebellum, anterior superior temporal gyrus, and planum polare. Greater activity for the singing over the speech condition for both the listening and covert production tasks was found in the right planum temporale. Greater activity in brain regions involved with consonance, orbitofrontal cortex (listening task), subcallosal cingulate (covert production task) were also present for singing over speech. The results are consistent with the PT mediating representational transformation across auditory and motor domains in response to consonance for singing over that of speech. Hemispheric laterality was assessed by paired t tests between active voxels in the contrast of interest relative to the left-right flipped contrast of interest calculated from images normalized to the left-right reflected template. Consistent with some hypotheses regarding hemispheric specialization, a pattern of differential laterality for speech over singing (both covert production and listening tasks) occurs in the left temporal lobe, whereas, singing over speech (listening task only) occurs in right temporal lobe.

A 100-Year Review: Stress physiology including heat stress.

PubMed

Collier, R J; Renquist, B J; Xiao, Y

2017-12-01

Stress is an external event or condition that places a strain on a biological system. The animal response to a stress involves the expenditure of energy to remove or reduce the impact of the stress. This increases maintenance requirements of the animal and results in loss of production. The biological response to stress is divided into acute and chronic phases, with the acute phase lasting hours to a few days and the chronic phase lasting several days to weeks. The acute response is driven by homeostatic regulators of the nervous and endocrine systems and the chronic phase by homeorhetic regulators of the endocrine system. Both responses involve alterations in energy balance and metabolism. Thermal environment affects all animals and therefore represents the largest single stressor in animal production. Other types of stressors include housing conditions, overcrowding, social rank, disease, and toxic compounds. "Acclimation" to a stress is a phenotypic response developed by the animal to an individual stressor within the environment. However, under natural conditions, it is rare for only one environmental variable to change over time. "Acclimatization" is the process by which an animal adapts to several stressors within its natural environment. Acclimation is a homeorhetic process that takes several weeks to occur and occurs via homeorhetic, not homeostatic, mechanisms. It is a phenotypic change that disappears when the stress is removed. When the stress is severe and not relieved by acclimatization or management changes, the animal is considered chronically stressed and is susceptible to increased incidence of disease and poor health. Milk yield and reproduction are extremely sensitive to stress because of the high energy and protein demands of lactation and the complexity of the reproductive process and multiple organs that are involved. Improvements in protection of animals against stress require improved education of producers to recognize stress and methods for estimating degree of stress on animals. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

RNA-Seq reveals genotype-specific molecular responses to water deficit in eucalyptus

PubMed Central

2011-01-01

Background In a context of climate change, phenotypic plasticity provides long-lived species, such as trees, with the means to adapt to environmental variations occurring within a single generation. In eucalyptus plantations, water availability is a key factor limiting productivity. However, the molecular mechanisms underlying the adaptation of eucalyptus to water shortage remain unclear. In this study, we compared the molecular responses of two commercial eucalyptus hybrids during the dry season. Both hybrids differ in productivity when grown under water deficit. Results Pyrosequencing of RNA extracted from shoot apices provided extensive transcriptome coverage - a catalog of 129,993 unigenes (49,748 contigs and 80,245 singletons) was generated from 398 million base pairs, or 1.14 million reads. The pyrosequencing data enriched considerably existing Eucalyptus EST collections, adding 36,985 unigenes not previously represented. Digital analysis of read abundance in 14,460 contigs identified 1,280 that were differentially expressed between the two genotypes, 155 contigs showing differential expression between treatments (irrigated vs. non irrigated conditions during the dry season), and 274 contigs with significant genotype-by-treatment interaction. The more productive genotype displayed a larger set of genes responding to water stress. Moreover, stress signal transduction seemed to involve different pathways in the two genotypes, suggesting that water shortage induces distinct cellular stress cascades. Similarly, the response of functional proteins also varied widely between genotypes: the most productive genotype decreased expression of genes related to photosystem, transport and secondary metabolism, whereas genes related to primary metabolism and cell organisation were over-expressed. Conclusions For the most productive genotype, the ability to express a broader set of genes in response to water availability appears to be a key characteristic in the maintenance of biomass growth during the dry season. Its strategy may involve a decrease of photosynthetic activity during the dry season associated with resources reallocation through major changes in the expression of primary metabolism associated genes. Further efforts will be needed to assess the adaptive nature of the genes highlighted in this study. PMID:22047139

Effects of environmental variation during seed production on seed dormancy and germination.

PubMed

Penfield, Steven; MacGregor, Dana R

2017-02-01

The environment during seed production has major impacts on the behaviour of progeny seeds. It can be shown that for annual plants temperature perception over the whole life history of the mother can affect the germination rate of progeny, and instances have been documented where these affects cross whole generations. Here we discuss the current state of knowledge of signal transduction pathways controlling environmental responses during seed production, focusing both on events that take place in the mother plant and those that occur directly as a result of environmental responses in the developing zygote. We show that seed production environment effects are complex, involving overlapping gene networks active independently in fruit, seed coat, and zygotic tissues that can be deconstructed using careful physiology alongside molecular and genetic experiments. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Essential veterinary education in the cultural, political and biological complexities of international trade in animals and animal products.

PubMed

Brown, C C

2009-08-01

Globalisation has changed the veterinary profession in many ways and academic institutes may need to re-tool to help future professionals deal with the changes in a successful and productive way. The remarkably expanded and expanding volume of trade and traffic in animals and animal products means that to be effective veterinarians must grasp some of the complexities inherent in this trade. Being able to engage productively in cross-cultural dialogue will be important in negotiations over livestock shipments and also within the context of the delivery of medical services to companion animals in societies that are becoming increasingly diverse. Understanding the political landscapes that influence trade decisions will help to expedite agreements and facilitate the transfer of goods and materials that involve animal health. Disease emergence will continue to occur, and an awareness of the factors responsible and the response measures to undertake will help to contain any damage.

Enhanced interleukin-4 production in CD4+ T cells and elevated immunoglobulin E levels in antigen-primed mice by bisphenol A and nonylphenol, endocrine disruptors: involvement of nuclear factor-AT and Ca2+

PubMed Central

Lee, Mee H; Chung, Su W; Kang, Bok Y; Park, Jin; Lee, Choon H; Hwang, Seung Y; Kim, Tae S

2003-01-01

Bisphenol A (BPA) and p-nonylphenol (NP) are representative endocrine disruptors (EDs) that may have adverse effects on human health. The influence of these compounds on allergic immune responses remains unclear. In this study, we have examined the effects of BPA and NP on production of interleukin-4 (IL-4), a pro-inflammatory cytokine closely associated with allergic immune responses. Both BPA and NP significantly enhanced IL-4 production in keyhole limpet haemocyanin (KLH)-primed CD4+ T cells in a concentration-dependent manner. Treatment with BPA or NP in vivo resulted in significant increase of IL-4 production in CD4+ T cells and of antigen-specific immunoglobulin E (IgE) levels in the sera of KLH-primed mice. Furthermore, BPA and NP enhanced the activation of IL-4 gene promoter in EL4 T cells transiently transfected with IL-4 promoter/reporter constructs, and the enhancing effect mapped to a region in the IL-4 promoter containing binding sites for nuclear factor (NF)-AT. Activation of T lymphocytes by phorbol 12-myristate 13-acetate/ionomycin resulted in markedly enhanced binding activities to the NF-AT site, which significantly increased upon addition of BPA or NP, as demonstrated by the electrophoretic mobility shift assay, indicating that the transcription factor NF-AT was involved in the enhancing effect of BPA and NP on IL-4 production. The enhancement of IL-4 production by BPA or NP was significantly reduced by nitrendipine, a blocker of Ca2+ influx, and by FK506, a calcineurin inhibitor. FK506 inhibited the NF-AT–DNA binding activity and IL-4 gene promoter activity enhanced by BPA or NP. These results represent the first report describing possible enhancement of allergic response by EDs through increasing IL-4 production in CD4+ T cells and antigen-specific IgE levels in the sera via the stimulation of Ca2+/calcineurin-dependent NF-AT activation. PMID:12709020

Supply chain carbon footprinting and responsibility allocation under emission regulations.

PubMed

Chen, Jin-Xiao; Chen, Jian

2017-03-01

Reduction of greenhouse gas emissions has become an enormous challenge for any single enterprise and its supply chain because of the increasing concern on global warming. This paper investigates carbon footprinting and responsibility allocation for supply chains involved in joint production. Our study is conducted from the perspective of a social planner who aims to achieve social value optimization. The carbon footprinting model is based on operational activities rather than on firms because joint production blurs the organizational boundaries of footprints. A general model is proposed for responsibility allocation among firms who seek to maximize individual profits. This study looks into ways for the decentralized supply chain to achieve centralized optimality of social value under two emission regulations. Given a balanced allocation for the entire supply chain, we examine the necessity of over-allocation to certain firms under specific situations and find opportunities for the firms to avoid over-allocation. The comparison of the two regulations reveals that setting an emission standard per unit of product will motivate firms to follow the standard and improve their emission efficiencies. Hence, a more efficient and promising policy is needed in contrast to existing regulations on total production. Copyright © 2016 Elsevier Ltd. All rights reserved.

Microarray Meta-Analysis Focused on the Response of Genes Involved in Redox Homeostasis to Diverse Abiotic Stresses in Rice

PubMed Central

de Abreu Neto, Joao B.; Frei, Michael

2016-01-01

Plants are exposed to a wide range of abiotic stresses (AS), which often occur in combination. Because physiological investigations typically focus on one stress, our understanding of unspecific stress responses remains limited. The plant redox homeostasis, i.e., the production and removal of reactive oxygen species (ROS), may be involved in many environmental stress conditions. Therefore, this study intended to identify genes, which are activated in diverse AS, focusing on ROS-related pathways. We conducted a meta-analysis (MA) of microarray experiments, focusing on rice. Transcriptome data were mined from public databases and fellow researchers, which represented 36 different experiments and investigated diverse AS, including ozone stress, drought, heat, cold, salinity, and mineral deficiencies/toxicities. To overcome the inherent artifacts of different MA methods, data were processed using Fisher, rOP, REM, and product of rank (GeneSelector), and genes identified by most approaches were considered as shared differentially expressed genes (DEGs). Two MA strategies were adopted: first, datasets were separated into shoot, root, and seedling experiments, and these tissues were analyzed separately to identify shared DEGs. Second, shoot and seedling experiments were classed into oxidative stress (OS), i.e., ozone and hydrogen peroxide treatments directly producing ROS in plant tissue, and other AS, in which ROS production is indirect. In all tissues and stress conditions, genes a priori considered as ROS-related were overrepresented among the DEGs, as they represented 4% of all expressed genes but 7–10% of the DEGs. The combined MA approach was substantially more conservative than individual MA methods and identified 1001 shared DEGs in shoots, 837 shared DEGs in root, and 1172 shared DEGs in seedlings. Within the OS and AS groups, 990 and 1727 shared DEGs were identified, respectively. In total, 311 genes were shared between OS and AS, including many regulatory genes. Combined co-expression analysis identified among those a cluster of 42 genes, many involved in the photosynthetic apparatus and responsive to drought, iron deficiency, arsenic toxicity, and ozone. Our data demonstrate the importance of redox homeostasis in plant stress responses and the power of MA to identify candidate genes underlying unspecific signaling pathways. PMID:26793229

Hyperhomocysteinemia impairs regional blood flow: involvements of endothelial and neuronal nitric oxide.

PubMed

Toda, Noboru; Okamura, Tomio

2016-09-01

Increasing evidence support the idea that hyperhomocysteinemia (HHcy) is responsible for pathogenesis underlying cerebral, coronary, renal, and other vascular circulatory disorders and for hypertension. Impaired synthesis of nitric oxide (NO) in the endothelium or increased production of asymmetric dimethylarginine and activated oxygen species are involved in the impairment of vasodilator effects of NO. Impaired circulation in the brain derived from reduced synthesis and actions of NO would be an important triggering factor to dementia and Alzheimer's disease. Reduced actions of NO and brain hypoperfusion trigger increased production of amyloid-β that inhibits endothelial function, thus establishing a vicious cycle for impairing brain circulation. HHcy is involved in the genesis of anginal attack and coronary myocardial infarction. HHcy is also involved in renal circulatory diseases. The homocysteine (Hcy)-induced circulatory failure is promoted by methionine and is prevented by increased folic acid and vitamin B6/B12. Eliminating poor life styles, such as smoking and being sedentary; keeping favorable dietary habits; and early treatment maintaining constitutive NOS functions healthy, reducing oxidative stresses would be beneficial in protecting HHcy-induced circulatory failures.

Immunomodulatory effects of Bacteroides products on in vitro human lymphocyte functions.

PubMed

Shenker, B J; Slots, J

1989-03-01

Bacteroides spp. have been implicated in the pathogenesis of several diseases, including periodontal diseases. In this study sonic extracts of 6 Bacteroides spp. were examined for their abilities to alter human lymphocyte function. We found that soluble extracts from Bacteroides intermedius, Bacteroides endodontalis, Bacteroides asaccharolyticus, Bacteroides melaninogenicus, and to a lesser degree Bacteroides loescheii, caused dose-dependent inhibition of human lymphocyte responsiveness to both mitogens and antigens. Suppression involved altered DNA, RNA and protein synthesis as well as immunoglobulin production. In contrast, Bacteroides gingivalis did not suppress these responses; instead, it stimulated lymphocyte proliferation and enhanced immunoglobulin production. It has been proposed that impaired host defense may play a pivotal role in the pathogenesis of many infections. The data presented in this paper suggest that microbial mediated immunosuppression may conceivably alter the nature and consequences of host-parasite interactions in periodontal disease.

Enhancing lithium-sulphur battery performance by strongly binding the discharge products on amino-functionalized reduced graphene oxide.

PubMed

Wang, Zhiyu; Dong, Yanfeng; Li, Hongjiang; Zhao, Zongbin; Wu, Hao Bin; Hao, Ce; Liu, Shaohong; Qiu, Jieshan; Lou, Xiong Wen David

2014-09-25

Lithium-sulphur batteries are one very appealing power source with high energy density. But their practical use is still hindered by several issues including short lifespan, low efficiency and safety concern from the lithium anode. Polysulphide dissolution and insulating nature of sulphur are generally considered responsible for the capacity degradation. However, the detachment of discharge products, that is, highly polar lithium sulphides, from nonpolar carbon matrix (for example, graphene) has been rarely studied as one critical factor. Here we report the strongly covalent stabilization of sulphur and its discharge products on amino-functionalized reduced graphene oxide that enables stable capacity retention of 80% for 350 cycles with high capacities and excellent high-rate response up to 4 C. The present study demonstrates a feasible and effective strategy to solve the long-term cycling difficulty for lithium-sulphur batteries and also helps to understand the capacity decay mechanism involved.

Neural Circuits Underlying Crying and Cry Responding in Mammals

PubMed Central

Newman, John D.

2007-01-01

Crying is a universal vocalization in human infants, as well as in the infants of other mammals. Little is known about the neural structures underlying cry production, or the circuitry that mediates a caregiver’s response to cry sounds. In this review, the specific structures known or suspected to be involved in this circuit are identified, along with neurochemical systems and hormones for which evidence suggests a role in responding to infants and infant cries. In addition, evidence that crying elicits parental responses in different mammals is presented. An argument is made for including ‘crying’ as a functional category in the vocal repertoire of all mammalian infants (and the adults of some species). The prevailing neural model for crying production considers forebrain structures to be dispensable. However, evidence for the anterior cingulate gyrus in cry production, and this structure along with the amygdala and some other forebrain areas in responding to cries is presented. PMID:17363076

Insight into the Genome of Staphylococcus xylosus, a Ubiquitous Species Well Adapted to Meat Products

PubMed Central

Leroy, Sabine; Vermassen, Aurore; Ras, Geoffrey; Talon, Régine

2017-01-01

Staphylococcus xylosus belongs to the vast group of coagulase-negative staphylococci. It is frequently isolated from meat products, either fermented or salted and dried, and is commonly used as starter cultures in sausage manufacturing. Analysis of the S. xylosus genome together with expression in situ in a meat model revealed that this bacterium is well adapted to meat substrates, being able to use diverse substrates as sources of carbon and energy and different sources of nitrogen. It is well-equipped with genes involved in osmotic, oxidative/nitrosative, and acidic stress responses. It is responsible for the development of the typical colour of cured meat products via its nitrate reductase activity. It contributes to sensorial properties, mainly by the the catabolism of pyruvate and amino acids resulting in odorous compounds and by the limiting of the oxidation of fatty acids, thereby avoiding rancidity. PMID:28850086

Pupillary dynamics reveal computational cost in sentence planning.

PubMed

Sevilla, Yamila; Maldonado, Mora; Shalóm, Diego E

2014-01-01

This study investigated the computational cost associated with grammatical planning in sentence production. We measured people's pupillary responses as they produced spoken descriptions of depicted events. We manipulated the syntactic structure of the target by training subjects to use different types of sentences following a colour cue. The results showed higher increase in pupil size for the production of passive and object dislocated sentences than for active canonical subject-verb-object sentences, indicating that more cognitive effort is associated with more complex noncanonical thematic order. We also manipulated the time at which the cue that triggered structure-building processes was presented. Differential increase in pupil diameter for more complex sentences was shown to rise earlier as the colour cue was presented earlier, suggesting that the observed pupillary changes are due to differential demands in relatively independent structure-building processes during grammatical planning. Task-evoked pupillary responses provide a reliable measure to study the cognitive processes involved in sentence production.

Task-dependent modulations of prefrontal and hippocampal activity during intrinsic word production.

PubMed

Whitney, Carin; Weis, Susanne; Krings, Timo; Huber, Walter; Grossman, Murray; Kircher, Tilo

2009-04-01

Functional imaging studies of single word production have consistently reported activation of the lateral prefrontal and cingulate cortex. Its contribution has been shown to be sensitive to task demands, which can be manipulated by the degree of response specification. Compared with classical verbal fluency, free word association relies less on response restrictions but to a greater extent on associative binding processes, usually subserved by the hippocampus. To elucidate the relevance of the frontal and medial-temporal areas during verbal retrieval tasks, we applied varying degrees of response specification. During fMRI data acquisition, 18 subjects performed a free verbal association (FVA), a semantic verbal fluency (SVF) task, and a phonological verbal fluency (PVF) task. Externally guided word production served as a baseline condition to control for basic articulatory and reading processes. As expected, increased brain activity was observed in the left lateral and bilateral medial frontal cortices for SVF and PVF. The anterior cingulate gyrus was the only structure common to both fluency tasks in direct comparison to the less restricted FVA task. The hippocampus was engaged during associative and semantic retrieval. Interestingly, hippocampal activity was selectively evident during FVA in direct comparison to SVF when it was controlled for stimulus-response relations. The current data confirm the role of the left prefrontal-cingulate network in constrained word production. Hippocampal activity during spontaneous word production is a novel finding and seems to be dependent on the retrieval process (free vs. constrained) rather than the variety of stimulus-response relationships that is involved.

Proceedings of the first switch tube advanced technology meeting held at EG G, Salem, Massachusetts, May 23, 1990

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

Shuman, A.; Beavis, L.

Early in 1990, J. A. Wilder, Supervisor of Sandia National Laboratories (SNLA), Division 2565 requested that a meeting of the scientists and engineers responsible for developing and producing switch tubes be set up to discuss in a semi-formal way the science and technology of switch tubes. Programmatic and administrative issues were specifically exempted from the discussions. L. Beavis, Division 7471, SNL and A. Shuman, EG G, Salem were made responsible for organizing a program including the materials and processes of switch tubes. The purpose of the Switch Tube Advanced Technology meeting was to allow personnel from Allied Signal Kansas Citymore » Division (AS/KCD); EG G, Salem and Sandia National Laboratories (SNL) to discuss a variety of issues involved in the development and production of switch tubes. It was intended that the formal and informal discussions would allow a better understanding of the production problems by material and process engineers and of the materials and processes by production engineers. This program consisted of formal presentations on May 23 and informal discussions on May 24. The topics chosen for formal presentation were suggested by the people of AS/KCD, EG G, Salem, and SNL involved with the design, development and production of switch tubes. The topics selected were generic. They were not directed to any specific switch tube but rather to all switch tubes in production and development. This document includes summaries of the material presented at the formal presentation on May 23.« less

Precision metabolic engineering: The design of responsive, selective, and controllable metabolic systems.

PubMed

McNerney, Monica P; Watstein, Daniel M; Styczynski, Mark P

2015-09-01

Metabolic engineering is generally focused on static optimization of cells to maximize production of a desired product, though recently dynamic metabolic engineering has explored how metabolic programs can be varied over time to improve titer. However, these are not the only types of applications where metabolic engineering could make a significant impact. Here, we discuss a new conceptual framework, termed "precision metabolic engineering," involving the design and engineering of systems that make different products in response to different signals. Rather than focusing on maximizing titer, these types of applications typically have three hallmarks: sensing signals that determine the desired metabolic target, completely directing metabolic flux in response to those signals, and producing sharp responses at specific signal thresholds. In this review, we will first discuss and provide examples of precision metabolic engineering. We will then discuss each of these hallmarks and identify which existing metabolic engineering methods can be applied to accomplish those tasks, as well as some of their shortcomings. Ultimately, precise control of metabolic systems has the potential to enable a host of new metabolic engineering and synthetic biology applications for any problem where flexibility of response to an external signal could be useful. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Compensation for pitch-shifted auditory feedback during the production of Mandarin tone sequences

NASA Astrophysics Data System (ADS)

Xu, Yi; Larson, Charles R.; Bauer, Jay J.; Hain, Timothy C.

2004-08-01

Recent research has found that while speaking, subjects react to perturbations in pitch of voice auditory feedback by changing their voice fundamental frequency (F0) to compensate for the perceived pitch-shift. The long response latencies (150-200 ms) suggest they may be too slow to assist in on-line control of the local pitch contour patterns associated with lexical tones on a syllable-to-syllable basis. In the present study, we introduced pitch-shifted auditory feedback to native speakers of Mandarin Chinese while they produced disyllabic sequences /ma ma/ with different tonal combinations at a natural speaking rate. Voice F0 response latencies (100-150 ms) to the pitch perturbations were shorter than syllable durations reported elsewhere. Response magnitudes increased from 50 cents during static tone to 85 cents during dynamic tone productions. Response latencies and peak times decreased in phrases involving a dynamic change in F0. The larger response magnitudes and shorter latency and peak times in tasks requiring accurate, dynamic control of F0, indicate this automatic system for regulation of voice F0 may be task-dependent. These findings suggest that auditory feedback may be used to help regulate voice F0 during production of bi-tonal Mandarin phrases.

Interleukin-17A correlates with interleukin-6 production in human cystic echinococcosis: a possible involvement of IL-17A in immunoprotection against Echinococcus granulosus infection.

PubMed

Mezioug, Dalila; Touil-Boukoffa, Chafia

2012-01-01

Hydatidosis is a parasitic disease caused by the development, in humans and other mammals, of the larval form of Taenia, Echinococcus granulosus. It is one of the world's major zoonotic infections. This study aimed to examine interleukin-6 (IL-6), interferon-γ (IFN-γ) and interleukin-17A (IL-17A) production in patients with cystic echinococcosis (CE), and the role of IL-17A in the modulation of the immune response against the extracellular parasite, E. granulosus. A relationship between IL-6, IL-17A production and C reactive Protein (CRP) levels was also assessed. IL-6, IFN-γ, IL-17A and CRP production were determined in serum from Algerian hydatid patients. Cytokine production was also measured in supernatants from cultures of peripheral blood mononuclear cells (PBMCs) from hydatid patients stimulated by a major parasitic antigen (antigen-5). The increased activity of IL-6, IFN-γ and IL-17A were observed in most serum samples from patients. In contrast, healthy controls showed only minor levels. Similarly, high levels of CRP were detected. Our in vitro results indicate a positive correlation between IL-6, IFN-γ and IL-17A production in PBMC culture supernatants. However, IL-6, IFN-γ and IL-17A activity was low in serum and supernatants of PBMC cultures from relapsing patients, and there was no evidence of an immune response against parasitic antigen. Collectively, our results show that IL-17A was produced during human cystic echinococcosis, and was involved in the host defense mechanisms against the extracellular parasite E. granulosus. Our data suggest that IL-17A plays an immunoprotective role in this parasitic, helminth infection.

The host immune response to gastrointestinal nematode infection in sheep.

PubMed

McRae, K M; Stear, M J; Good, B; Keane, O M

2015-12-01

Gastrointestinal nematode infection represents a major threat to the health, welfare and productivity of sheep populations worldwide. Infected lambs have a reduced ability to absorb nutrients from the gastrointestinal tract, resulting in morbidity and occasional mortality. The current chemo-dominant approach to nematode control is considered unsustainable due to the increasing incidence of anthelmintic resistance. In addition, there is growing consumer demand for food products from animals not subjected to chemical treatment. Future mechanisms of nematode control must rely on alternative, sustainable strategies such as vaccination or selective breeding of resistant animals. Such strategies take advantage of the host's natural immune response to nematodes. The ability to resist gastrointestinal nematode infection is considered to be dependent on the development of a protective acquired immune response, although the precise immune mechanisms involved in initiating this process remain to be fully elucidated. In this study, current knowledge on the innate and acquired host immune response to gastrointestinal nematode infection in sheep and the development of immunity is reviewed. © 2015 John Wiley & Sons Ltd.

Immune response and milk production of dairy cows fed graded levels of rumen-protected glutamine.

PubMed

Caroprese, M; Albenzio, M; Marino, R; Santillo, A; Sevi, A

2012-08-01

The objective of the study was to determine the effects of dietary supplementation with glutamine on the immune function and milk production of dairy cows. The experiment involved 24 Friesian cows, divided into three groups of eight each, according to the level of rumen-protected glutamine supplementation: a diet with no supplementation (Control), a diet supplemented with 160 g/day/cow (G160) and a diet supplemented with 320 g/day/cow (G320). At 0, 30, and 60 days of the experiment, lymphocyte response to phytohemoagglutinin (PHA) was determined in vivo for each animal. Humoral response to chicken egg albumin (OVA) and interleukin - (IL)-1β, IL-6 and IL-10 plasma levels were measured at 0, 15, 30, 45, and 60 days. Results demonstrate that supplementing 160 g/day/cow of glutamine can modulate immune responses of dairy cows and enhance the amino acid profile of cow milk. Copyright © 2011. Published by Elsevier India Pvt Ltd.

Cystine improves survival rates in a LPS-induced sepsis mouse model.

PubMed

Tanaka, Kenji A K; Kurihara, Shigekazu; Shibakusa, Tetsuro; Chiba, Yasumasa; Mikami, Takashi

2015-12-01

The control of inflammation is important for suppressing severe sepsis. Oral administration of cystine and theanine have been shown to suppress inflammatory responses due to invasion. Furthermore, the uptake of cystine into monocytes is promoted by exposure to lipopolysaccharide (LPS). In the present study, the effects of cystine were examined in the context of inflammatory responses. Cystine was orally administered to mice, and the levels of interleukin (IL)-6 in the blood and spleen and the survival rates were calculated after the administration of LPS. The effects of cystine as well as neutralising anti-IL-10 antibodies on the LPS-induced production of IL-6 and IL-10 were examined in a monocyte cell line. The oral administration of cystine reduced IL-6 levels in the blood and spleen after LPS stimulation and improved survival rates. The addition of cystine to monocytes suppressed LPS-induced IL-6 production but enhanced IL-10 production. A neutralising anti-IL-10 antibody eliminated the inhibitory effects of cystine on the LPS-induced production of IL-6. The oral administration of cystine suppressed IL-6 production following LPS stimulation and improved survival rates in mice with LPS-induced sepsis. The enhanced production of IL-10 by monocytes may be involved in this anti-inflammatory response. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

[Impairment of the immune system caused by drugs].

PubMed

Pichler, W J

1987-03-21

The immune response and the ensuing inflammation relies on a complex interaction of cells and mediators. Various drugs can interfere with individual steps of the immune response, and in so doing they often imitate regulatory mechanisms of the immune system itself. The immunosuppressive effect of corticosteroids is based on changes in cell migration, reduced responsiveness of monocytes/macrophages to various stimuli and diminished production of interleukin-2. Cyclosporin A appears to block prolactin binding to prolactin receptors on lymphocytes, thus interfering with the immunostimulatory effect of prolactin. It also appears to have a Calmodulin antagonism and might thus block lymphokine production. Anticoagulants may block delayed type hypersensitivity reactions, since activation of the coagulation cascade is involved in this type of immune reaction. Attempts to use calcium channel blockers as immunosuppressive agents, or to take advantage of the immunoregulatory effects of adrenergic substances/blockers or other neurotransmitters, are of experimental value only.

Nitric oxide functions as a signal in plant disease resistance.

PubMed

Delledonne, M; Xia, Y; Dixon, R A; Lamb, C

1998-08-06

Recognition of an avirulent pathogen triggers the rapid production of the reactive oxygen intermediates superoxide (O2-) and hydrogen peroxide (H2O2). This oxidative burst drives crosslinking of the cell wall, induces several plant genes involved in cellular protection and defence, and is necessary for the initiation of host cell death in the hypersensitive disease-resistance response. However, this burst is not enough to support a strong disease-resistance response. Here we show that nitric oxide, which acts as a signal in the immune, nervous and vascular systems, potentiates the induction of hypersensitive cell death in soybean cells by reactive oxygen intermediates and functions independently of such intermediates to induce genes for the synthesis of protective natural products. Moreover, inhibitors of nitric oxide synthesis compromise the hypersensitive disease-resistance response of Arabidopsis leaves to Pseudomonas syringae, promoting disease and bacterial growth. We conclude that nitric oxide plays a key role in disease resistance in plants.

Response surface optimization of medium components for naringinase production from Staphylococcus xylosus MAK2.

PubMed

Puri, Munish; Kaur, Aneet; Singh, Ram Sarup; Singh, Anubhav

2010-09-01

Response surface methodology was used to optimize the fermentation medium for enhancing naringinase production by Staphylococcus xylosus. The first step of this process involved the individual adjustment and optimization of various medium components at shake flask level. Sources of carbon (sucrose) and nitrogen (sodium nitrate), as well as an inducer (naringin) and pH levels were all found to be the important factors significantly affecting naringinase production. In the second step, a 22 full factorial central composite design was applied to determine the optimal levels of each of the significant variables. A second-order polynomial was derived by multiple regression analysis on the experimental data. Using this methodology, the optimum values for the critical components were obtained as follows: sucrose, 10.0%; sodium nitrate, 10.0%; pH 5.6; biomass concentration, 1.58%; and naringin, 0.50% (w/v), respectively. Under optimal conditions, the experimental naringinase production was 8.45 U/mL. The determination coefficients (R(2)) were 0.9908 and 0.9950 for naringinase activity and biomass production, respectively, indicating an adequate degree of reliability in the model.

Transcriptome Analysis of Spartina pectinata in Response to Freezing Stress

PubMed Central

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

2016-01-01

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

Tell it to a child! A brain stimulation study of the role of left inferior frontal gyrus in emotion regulation during storytelling.

PubMed

Urgesi, Cosimo; Mattiassi, Alan D A; Buiatti, Tania; Marini, Andrea

2016-08-01

In everyday life we need to continuously regulate our emotional responses according to their social context. Strategies of emotion regulation allow individuals to control time, intensity, nature and expression of emotional responses to environmental stimuli. The left inferior frontal gyrus (LIFG) is involved in the cognitive control of the selection of semantic content. We hypothesized that it might also be involved in the regulation of emotional feelings and expressions. We applied continuous theta burst stimulation (cTBS) over LIFG or a control site before a newly-developed ecological regulation task that required participants to produce storytelling of pictures with negative or neutral valence to either a peer (unregulated condition) or a child (regulated condition). Linguistic, expressive, and physiological responses were analyzed in order to assess the effects of LIFG-cTBS on emotion regulation. Results showed that the emotion regulation context modulated the emotional content of narrative productions, but not the physiologic orienting response or the early expressive behavior to negative stimuli. Furthermore, LIFG-cTBS disrupted the text-level structuring of negative picture storytelling and the early cardiac and muscular response to negative pictures; however, it did not affect the contextual emotional regulation of storytelling. These results may suggest that LIFG is involved in the initial detection of the affective arousal of emotional stimuli. Copyright © 2016 Elsevier Inc. All rights reserved.

Cryptogein-Induced Transcriptional Reprogramming in Tobacco Is Light Dependent1[C][W

PubMed Central

Hoeberichts, Frank A.; Davoine, Céline; Vandorpe, Michaël; Morsa, Stijn; Ksas, Brigitte; Stassen, Catherine; Triantaphylidès, Christian; Van Breusegem, Frank

2013-01-01

The fungal elicitor cryptogein triggers a light-dependent hypersensitive response in tobacco (Nicotiana tabacum). To assess the effect of light on this nonhost resistance in more detail, we studied various aspects of the response under dark and light conditions using the tobacco-cryptogein experimental system. Here, we show that light drastically alters the plant’s transcriptional response to cryptogein, notably by dampening the induction of genes involved in multiple processes, such as ethylene biosynthesis, secondary metabolism, and glutathione turnover. Furthermore, chlorophyll fluorescence measurements demonstrated that quantum yield and functioning of the light-harvesting antennae decreased simultaneously, indicating that photoinhibition underlies the observed decreased photosynthesis and that photooxidative damage might be involved in the establishment of the altered response. Analysis of the isomer distribution of hydroxy fatty acids illustrated that, in the light, lipid peroxidation was predominantly due to the production of singlet oxygen. Differences in (reduced) glutathione concentrations and the rapid development of symptoms in the light when cryptogein was coinfiltrated with glutathione biosynthesis inhibitors suggest that glutathione might become a limiting factor during the cryptogein-induced hypersensitive response in the dark and that this response might be modified by an increased antioxidant availability in the light. PMID:23878079

Understanding Fluid Shifts in the Brain: Choroidal Regulation Involved in the Cerebral Fluid Response to Altered Gravity

NASA Technical Reports Server (NTRS)

Gabrion, Jaqueline; Vasques, Marilyn; Aquilina, Rudy (Technical Monitor)

2002-01-01

Fluid balance and regulation of body fluid production are critical aspects of life and survival on Earth. In space, without gravity exerting its usual downward pulling effect, the fluids of the human body shift in an unnatural, headward direction. After awhile, humans and other mammalian species adapt to the microgravity environment which leads to changes in the regulation and distribution of these body fluids. Previous spaceflight experiments have indicated that production of fluid in the brain and spinal cord, cerebrospinal fluid (CSF), might be reduced in rats exposed to microgravity. In this experiment conducted by Dr. Jacqueline Gabrion (University of Pierre and Marie Curie, France), proteins important for CSF production, and several molecules that regulate water and mineral transport, will be investigated in rats flown on the Shuttle. Dr. Gabrion and her team will determine the amounts of these proteins and molecules present in the brain in order to evaluate whether any changes have taken place during the rats' adaptation to microgravity. The levels of different aquaporins (proteins that act as a channel for water transport in and out of cells) will also be investigated in other areas of the brain and body to better understand the regulatory responses affecting these important water channel proteins. In addition to producing essential and basic information about fluid production in the brain and body, this experiment will reveal fundamental information about the mechanisms involved in cerebral adaptation and fluid balance during spaceflight.

Recombinant LipL32 stimulates interferon-gamma production in cattle vaccinated with a monovalent Leptospira borgpetersenii serovar Hardjo subtype Hardjobovis vaccine.

PubMed

Deveson Lucas, Deanna S; Lo, Miranda; Bulach, Dieter M; Quinsey, Noelene S; Murray, Gerald L; Allen, Andy; Adler, Ben

2014-03-14

Leptospira borgpetersenii serovar Hardjo subtype Hardjobovis (Hardjobovis) is the main causative agent of bovine leptospirosis in Australia, New Zealand, North America and elsewhere. Bovine leptospirosis can result in spontaneous abortion, stillbirth and reduced milk output. The organism is shed in the urine of infected animals and contact with contaminated materials can result in zoonotic infections in humans. Protective immunity in cattle against Hardjobovis involves stimulation of a Th1 cell mediated immune response, which can be characterized by the production of IFN-γ when blood from vaccinated animals is exposed to Hardjobovis antigens. However, the leptospiral components involved in stimulating this response have yet to be identified. In this study, 238 recombinant leptospiral proteins were evaluated for their ability to stimulate IFN-γ production in blood of cattle vaccinated with a commercial monovalent Hardjobovis vaccine. The conserved lipoprotein LipL32 is the major outer membrane protein of pathogenic Leptospira spp. A pool of soluble recombinant proteins which included LipL32, as well as LipL32 alone, stimulated significant IFN-γ production in blood of vaccinated cattle. A number of recombinant LipL32 fragments was generated, which identified the amino acids between 20 and 200 as containing the bovine T-cell reactive regions of LipL32. However, whether LipL32 plays a role in stimulating protective immunity in mammals has yet to be conclusively determined. Copyright © 2014 Elsevier B.V. All rights reserved.

Transcriptional profiling of Haemophilus parasuis SH0165 response to tilmicosin.

PubMed

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

2012-12-01

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

Activation of innate anti-viral immune response genes in symptomatic benign prostatic hyperplasia

PubMed Central

Madigan, Allison A.; Sobek, Kathryn M.; Cummings, Jessica L.; Green, William R.; Bacich, Dean J.; O’Keefe, Denise S.

2012-01-01

Benign Prostatic Hyperplasia (BPH)is the most common urologic disease in men over age 50. Symptoms include acute urinary retention, urgency to urinate and nocturia. For patients with severe symptoms, surgical treatment is used to remove the affected tissue. Interestingly, the presence of histologic BPH does not always correlate with symptoms. The molecular basis of symptomatic BPH and how it differs from asymptomatic BPH is unknown. Investigation into the molecular players involved in symptomatic BPH will likely give insight into novel therapeutic, and potentially preventative, targets. We determined the expression of genes involved in the innate anti-viral immune response in tissues from patients undergoing surgery to alleviate the symptoms of BPH, and compared the results to prostate tissue with histologic BPH, but from patients with few urinary issues (asymptomatic BPH). We found that expression of CFI, APOBEC3G, OAS2, and IFIT1, four genes whose protein products are involved in the innate anti-viral immune response, were significantly transcriptionally upregulated in symptomatic BPH. Additionally we observe hypomethylation and concomitant expression of ancient retroviral-like sequences, the LINE-1 retrotransposons, in symptomatic BPH when compared to normal prostate tissue. These findings merit further investigation into the anti-viral immune response in symptomatic BPH. PMID:22952051

CCR-2 neutralization augments murine fresh BMC activation by Staphylococcus aureus via two distinct mechanisms: at the level of ROS production and cytokine response.

PubMed

Nandi, Ajeya; Bishayi, Biswadev

2017-05-01

CCR-2 signaling regulates recruitment of monocytes from the bone marrow into the bloodstream and then to sites of infection. We sought to determine whether CCL-2/CCR-2 signaling is involved in the killing of Staphylococcus aureus by murine bone marrow cells (BMCs). The intermittent link of reactive oxygen species (ROS)-NF-κB/p38-MAPK-mediated CCL-2 production in CCR-2 signaling prompted us to determine whether neutralization of CCR-2 augments the response of murine fresh BMCs (FBMCs) after S. aureus infection. It was observed that anti-CCR-2 Ab-treated FBMCs released fewer ROS on encountering S. aureus infection than CCR-2 non-neutralized FBMCs, also correlating with reduced killing of S. aureus in CCR-2 neutralized FBMCs. Staphylococcal catalase and SOD were also found to play a role in protecting S. aureus from the ROS-mediated killing of FBMC. S. aureus infection of CCR-2 intact FBMCs pre-treated with either NF-κB or p-38-MAPK blocker induced less CCL-2, suggesting that NF-κB or p-38-MAPK is required for CCL-2 production by FBMCs. Moreover, blocking of CCR-2 along with NF-κB or p-38-MAPK resulted in elevated CCL-2 production and reduced CCR-2 expression. Inhibition of CCR-2 impairs the response of murine BMCs to S. aureus infection by attenuation ROS production and modulating the cytokine response.

Chrysolina herbacea Modulates Terpenoid Biosynthesis of Mentha aquatica L.

PubMed Central

Atsbaha Zebelo, Simon; Bertea, Cinzia M.; Bossi, Simone; Occhipinti, Andrea; Gnavi, Giorgio; Maffei, Massimo E.

2011-01-01

Interactions between herbivorous insects and plants storing terpenoids are poorly understood. This study describes the ability of Chrysolina herbacea to use volatiles emitted by undamaged Mentha aquatica plants as attractants and the plant's response to herbivory, which involves the production of deterrent molecules. Emitted plant volatiles were analyzed by GC-MS. The insect's response to plant volatiles was tested by Y-tube olfactometer bioassays. Total RNA was extracted from control plants, mechanically damaged leaves, and leaves damaged by herbivores. The terpenoid quantitative gene expressions (qPCR) were then assayed. Upon herbivory, M. aquatica synthesizes and emits (+)-menthofuran, which acts as a deterrent to C. herbacea. Herbivory was found to up-regulate the expression of genes involved in terpenoid biosynthesis. The increased emission of (+)-menthofuran was correlated with the upregulation of (+)-menthofuran synthase. PMID:21408066

Interleukin-4 production by Follicular Helper T cells requires the conserved Il4 enhancer HS V

PubMed Central

Vijayanand, Pandurangan; Seumois, Grégory; Simpson, Laura J.; Abdul-Wajid, Sarah; Baumjohann, Dirk; Panduro, Marisella; Huang, Xiaozhu; Interlandi, Jeneen; Djuretic, Ivana M.; Brown, Daniel R.; Sharpe, Arlene H.; Rao, Anjana; Ansel, K. Mark

2012-01-01

SUMMARY Follicular helper T cells (Tfh cells) are the major producers of interleukin-4 (IL-4) in secondary lymphoid organs where humoral immune responses develop. Il4 regulation in Tfh cells appears distinct from the classical T helper 2 (Th2) cell pathway, but the underlying molecular mechanisms remain largely unknown. We found that HS V (also known as CNS2), a 3’ enhancer in the Il4 locus, is essential for IL-4 production by Tfh cells. Mice lacking HS V display marked defects in Th2 humoral immune responses, as evidenced by abrogated IgE and sharply reduced IgG1 production in vivo. In contrast, effector Th2 cells that are involved in tissue responses were far less dependent on HS V. HS V facilitated removal of repressive chromatin marks during Th2 and Tfh cell differentiation, and increased accessibility of the Il4 promoter. Thus Tfh and Th2 cells utilize distinct but overlapping molecular mechanisms to regulate Il4, a finding with important implications for understanding the molecular basis of Th2 mediated allergic diseases. PMID:22326582

Identification of a response regulator involved in surface attachment, cell-cell aggregation, exopolysaccharide production and virulence in the plant pathogen Xylella fastidiosa.

PubMed

Voegel, Tanja M; Doddapaneni, Harshavardhan; Cheng, Davis W; Lin, Hong; Stenger, Drake C; Kirkpatrick, Bruce C; Roper, M Caroline

2013-04-01

Xylella fastidiosa, the causal agent of Pierce's disease of grapevine, possesses several two-component signal transduction systems that allow the bacterium to sense and respond to changes in its environment. Signals are perceived by sensor kinases that autophosphorylate and transfer the phosphate to response regulators (RRs), which direct an output response, usually by acting as transcriptional regulators. In the X. fastidiosa genome, 19 RRs were found. A site-directed knockout mutant in one unusual RR, designated XhpT, composed of a receiver domain and a histidine phosphotransferase output domain, was constructed. The resulting mutant strain was analysed for changes in phenotypic traits related to biofilm formation and gene expression using microarray analysis. We found that the xhpT mutant was altered in surface attachment, cell-cell aggregation, exopolysaccharide (EPS) production and virulence in grapevine. In addition, this mutant had an altered transcriptional profile when compared with wild-type X. fastidiosa in genes for several biofilm-related traits, such as EPS production and haemagglutinin adhesins. © 2012 BSPP AND BLACKWELL PUBLISHING LTD.

Differences on the projective hand test among chronic pain patients reporting three different pain experiences.

PubMed

Panek, Paul E; Skowronski, John J; Wagner, Edwin E

2002-10-01

This study examined personality differences among individuals experiencing 3 different types of pain. The projective Hand Test was administered to 90 individuals who were seeking treatment at a pain clinic in an urban area of the southeast United States. These people were seeking treatment for either arthritis (n = 31), fibromyalgia (n = 29), or migraine headaches (n = 30). A 2 (gender) x 3 (pain group) x Age Group multivariate analysis of variance was conducted using the quantitative Hand Test scoring variables as dependent measures. Results indicated that individuals who were seeking treatment for migraine headaches had a higher production rate of responses involving exhibitionistic displays (EXH) than individuals in the other 2 groups. Individuals who were seeking treatment for fibromyalgia had a higher production rate of responses indicating fear and phobic concerns (FEAR) than individuals in the other 2 groups. Individuals who were seeking treatment for arthritis had a higher production rate of Active (ACT) responses than individuals in the other 2 groups. Possible causes and consequences of these effects are discussed.

Emerging trends in the functional genomics of the abiotic stress response in crop plants.

PubMed

Vij, Shubha; Tyagi, Akhilesh K

2007-05-01

Plants are exposed to different abiotic stresses, such as water deficit, high temperature, salinity, cold, heavy metals and mechanical wounding, under field conditions. It is estimated that such stress conditions can potentially reduce the yield of crop plants by more than 50%. Investigations of the physiological, biochemical and molecular aspects of stress tolerance have been conducted to unravel the intrinsic mechanisms developed during evolution to mitigate against stress by plants. Before the advent of the genomics era, researchers primarily used a gene-by-gene approach to decipher the function of the genes involved in the abiotic stress response. However, abiotic stress tolerance is a complex trait and, although large numbers of genes have been identified to be involved in the abiotic stress response, there remain large gaps in our understanding of the trait. The availability of the genome sequences of certain important plant species has enabled the use of strategies, such as genome-wide expression profiling, to identify the genes associated with the stress response, followed by the verification of gene function by the analysis of mutants and transgenics. Certain components of both abscisic acid-dependent and -independent cascades involved in the stress response have already been identified. Information originating from the genome-wide analysis of abiotic stress tolerance will help to provide an insight into the stress-responsive network(s), and may allow the modification of this network to reduce the loss caused by stress and to increase agricultural productivity.

Physiological and transcriptomic responses in the seed coat of field-grown soybean (Glycine max L. Merr.) to abiotic stress.

PubMed

Leisner, Courtney P; Yendrek, Craig R; Ainsworth, Elizabeth A

2017-12-12

Understanding how intensification of abiotic stress due to global climate change affects crop yields is important for continued agricultural productivity. Coupling genomic technologies with physiological crop responses in a dynamic field environment is an effective approach to dissect the mechanisms underpinning crop responses to abiotic stress. Soybean (Glycine max L. Merr. cv. Pioneer 93B15) was grown in natural production environments with projected changes to environmental conditions predicted for the end of the century, including decreased precipitation, increased tropospheric ozone concentrations ([O 3 ]), or increased temperature. All three environmental stresses significantly decreased leaf-level photosynthesis and stomatal conductance, leading to significant losses in seed yield. This was driven by a significant decrease in the number of pods per node for all abiotic stress treatments. To understand the underlying transcriptomic response involved in the yield response to environmental stress, RNA-Sequencing analysis was performed on the soybean seed coat, a tissue that plays an essential role in regulating carbon and nitrogen transport to developing seeds. Gene expression analysis revealed 49, 148 and 1,576 differentially expressed genes in the soybean seed coat in response to drought, elevated [O 3 ] and elevated temperature, respectively. Elevated [O 3 ] and drought did not elicit substantive transcriptional changes in the soybean seed coat. However, this may be due to the timing of sampling and does not preclude impacts of those stresses on different tissues or different stages in seed coat development. Expression of genes involved in DNA replication and metabolic processes were enriched in the seed coat under high temperate stress, suggesting that the timing of events that are important for cell division and proper seed development were altered in a stressful growth environment.

Trpac1, a pH response transcription regulator, is involved in cellulase gene expression in Trichoderma reesei.

PubMed

He, Ronglin; Ma, Lijuan; Li, Chen; Jia, Wendi; Li, Demao; Zhang, Dongyuan; Chen, Shulin

2014-12-01

Fungi grow over a relatively wide pH range and adapt to extracellular pH through a genetic regulatory system mediated by a key component PacC, which is a pH transcription regulator. The cellulase production of the filamentous fungi Trichoderma reesei is sensitive to ambient pH. To investigate the connection between cellulase expression regulation and ambient pH, an ortholog of Aspergillus nidulans pacC, Trpac1, was identified and functionally characterized using a target gene deletion strategy. Deleting Trpac1 dramatically increased the cellulase production and the transcription levels of the major cellulase genes at neutral pH, which suggested Trpac1 is involved in the regulation of cellulase production. It was further observed that the expression levels of transcription factors xyr1 and ace2 also increased in the ΔTrpac1 mutant at neutral pH. In addition, the ΔTrpac1 mutant exhibited conidiation defects under neutral and alkaline pH. These results implied that Trpac1 in involved in growth and development process and cellulase gene expression in T. reesei. Copyright © 2014 Elsevier Inc. All rights reserved.

Parent attendance and homework adherence predict response to a family-school intervention for children with ADHD

PubMed Central

Clarke, Angela T.; Marshall, Stephen A.; Mautone, Jennifer A.; Soffer, Stephen L.; Jones, Heather A.; Costigan, Tracy E.; Patterson, Anwar; Jawad, Abbas F.; Power, Thomas J.

2013-01-01

Objective This study examined the relative contribution of two dimensions of parent engagement, attendance and homework adherence, to parent and child treatment response and explored whether early engagement was a stronger predictor of outcomes than later engagement. Method The sample consisted of parents of participants (n = 92; M age 9.4 years, SD = 1.27; 67% male; 69% White) in a 12-session evidence-based family-school intervention for children with ADHD. Attendance was assessed using clinician records, and homework adherence was measured by rating permanent products. Outcomes included parent and teacher ratings of family involvement in education, parenting practices, and child functioning. Results Accounting for the contributions of baseline scores and attendance, homework adherence was a significant predictor of parental self-efficacy, the parent-teacher relationship, parenting through positive involvement, and the child’s inattention to homework and homework productivity. Accounting for the contribution of baseline scores and homework adherence, attendance was a significant predictor of one outcome, the child’s academic productivity. Early homework adherence appeared to be more predictive of outcomes than later adherence, whereas attendance did not predict outcomes during either half of treatment. Conclusions These results indicate that, even in the context of evidence-based practice, it is the extent to which parents actively engage with treatment, rather than the number of sessions they attend, that is most important in predicting intervention response. Because attendance is limited as an index of engagement and a predictor of outcomes, increased efforts to develop interventions to promote parent adherence to behavioral interventions for children are warranted. PMID:23688140

Indirect effects of tending ants on holm oak volatiles and acorn quality

PubMed Central

Llusia, Joan; Peñuelas, Josep

2011-01-01

The indirect effect of ants on plants through their mutualism with honeydew-producing insects has been extensively investigated. Honeydew-producing insects that are tended by ants impose a cost on plant fitness and health by reducing seed production and/or plant growth. This cost is associated with sap intake and virus transmissions but may be overcompesated by tending ants if they deter or prey on hebivorous insects. The balance between cost and benefits depends on the tending ant species. In this study we report other indirect effects on plants of the mutualism between aphids and ants. We have found that two Lasius ant species, one native and the other invasive, may change the composition of volatile organic compounds (VOCs) of the holm oak (Quercus ilex) blend when they tend the aphid Lachnus roboris. The aphid regulation of its feeding and honeydew production according to the ant demands was proposed as a plausible mechanism that triggers changes in VOCs. Additionally, we now report here that aphid feeding, which is located most of the time on acorns cap or petiole, significantly increased the relative content of linolenic acid in acorns from holm oak colonized by the invasive ant. This acid is involved in the response of plants to insect herbivory as a precursor or jasmonic acid. No effect was found on acorn production, germination or seedlings quality. These results suggest that tending-ants may trigger the physiological response of holm oaks involved in plant resistance toward aphid herbivory and this response is ant species-dependent. PMID:21494087

Parent attendance and homework adherence predict response to a family-school intervention for children with ADHD.

PubMed

Clarke, Angela T; Marshall, Stephen A; Mautone, Jennifer A; Soffer, Stephen L; Jones, Heather A; Costigan, Tracy E; Patterson, Anwar; Jawad, Abbas F; Power, Thomas J

2015-01-01

This study examined the relative contribution of two dimensions of parent engagement, attendance and homework adherence, to parent and child treatment response and explored whether early engagement was a stronger predictor of outcomes than later engagement. The sample consisted of parents of participants (n = 92; M age = 9.4 years, SD = 1.27; 67% male, 69% White) in a 12-session evidence-based family-school intervention for children with attention-deficit/hyperactivity disorder. Attendance was assessed using clinician records, and homework adherence was measured by rating permanent products. Outcomes included parent and teacher ratings of family involvement in education, parenting practices, and child functioning. Accounting for the contributions of baseline scores and attendance, homework adherence was a significant predictor of parental self-efficacy, the parent-teacher relationship, parenting through positive involvement, and the child's inattention to homework and homework productivity. Accounting for the contribution of baseline scores and homework adherence, attendance was a significant predictor of one outcome, the child's academic productivity. Early homework adherence appeared to be more predictive of outcomes than later adherence, whereas attendance did not predict outcomes during either half of treatment. These results indicate that, even in the context of evidence-based practice, it is the extent to which parents actively engage with treatment, rather than the number of sessions they attend, that is most important in predicting intervention response. Because attendance is limited as an index of engagement and a predictor of outcomes, increased efforts to develop interventions to promote parent adherence to behavioral interventions for children are warranted.

Interferons and Interferon Regulatory Factors in Malaria

PubMed Central

Claser, Carla; Tan, Kevin Shyong Wei; Rénia, Laurent

2014-01-01

Malaria is one of the most serious infectious diseases in humans and responsible for approximately 500 million clinical cases and 500 thousand deaths annually. Acquired adaptive immune responses control parasite replication and infection-induced pathologies. Most infections are clinically silent which reflects on the ability of adaptive immune mechanisms to prevent the disease. However, a minority of these can become severe and life-threatening, manifesting a range of overlapping syndromes of complex origins which could be induced by uncontrolled immune responses. Major players of the innate and adaptive responses are interferons. Here, we review their roles and the signaling pathways involved in their production and protection against infection and induced immunopathologies. PMID:25157202

In vivo and in vitro IL-18 production during uveitis associated with Behçet disease: effect of glucocorticoid therapy.

PubMed

Belguendouz, H; Messaoudene, D; Lahmar-Belguendouz, K; Djeraba, Z; Otmani, F; Terahi, M; Tiar, M; Hartani, D; Lahlou-Boukoffa, O S; Touil-Boukoffa, C

2015-03-01

Uveitis represents one of the major diagnostic criteria in Behçet's disease. It is most prevalent in the countries of the Mediterranean area, including Algeria, and along the Silk Road. Clinical features include oral and genital ulcers, ocular and skin lesions, as well as central nervous system, joint, vascular, gastrointestinal, or pulmonary manifestations. Many studies have reported that Th1 immune responses are involved in the physiopathology. We have previously studied the production of IL-12 and IFN-γ, cytokine markers in the Th1 pathway involved in Behçet's disease. In our study, we investigate in vivo and in vitro IL-18 production in Algerian patients with Behçet's disease with ocular manifestations in various stages of the disease. We examined the effect of glucocorticoids on IL-18 production during the active stage of the disease. Our results suggest that IL-18 could be a good biomarker for monitoring disease activity and its regression, demonstrating the effectiveness of treatment on the underlying immunopathologic process. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A novel pathway of direct methane production and emission by eukaryotes including plants, animals and fungi: An overview

NASA Astrophysics Data System (ADS)

Liu, Jiangong; Chen, Huai; Zhu, Qiuan; Shen, Yan; Wang, Xue; Wang, Meng; Peng, Changhui

2015-08-01

Methane (CH4) is a powerful greenhouse gas with a global warming potential 28 times that of carbon dioxide (CO2). CH4 is responsible for approximately 20% of the Earth's warming since pre-industrial times. Knowledge of the sources of CH4 is crucial due to the recent substantial interannual variability of growth rates and uncertainties regarding individual sources. The prevailing paradigm is that methanogenesis carried out by methanogenic archaea occurs primarily under strictly anaerobic conditions. However, in the past decade, studies have confirmed direct CH4 release from three important kingdoms of eukaryotes-Plantae, Animalia and Fungi-even in the presence of oxygen. This novel CH4 production pathway has been aptly termed ;aerobic CH4 production; to distinguish it from the well-known anaerobic CH4 production pathway, which involves catalytic activity by methanogenic archaeal enzymes. In this review, we collated recent experimental evidence from the published literature and documented this novel pathway of direct CH4 production and emission by eukaryotes. The mechanisms involved in this pathway may be related to protective strategies of eukaryotes in response to changing environmental stresses, with CH4 a by-product or end-product during or at the end of the process(es) that originates from organic methyl-type compounds. Based on the existing, albeit uncertain estimates, plants seem to contribute less to the global CH4 budget (3-24%) compared to previous estimates (10-37%). We still lack estimates of CH4 emissions by animals and fungi. Overall, there is an urgent need to identify the precursors for this novel CH4 source and improve our understanding of the mechanisms of direct CH4 production and the impacts of environmental stresses. An estimate of this new CH4 source, which was not considered as a CH4 source by the Intergovernmental Panel on Climate Change (IPCC) (2013), could be useful for better quantitation of the global CH4 budget.

Quality of Working Life in the Automobile Industry: A Canada-UK Comparative Study.

ERIC Educational Resources Information Center

Lewchuk, Wayne; Stewart, Paul; Yates, Charlotte

2001-01-01

Surveys in five automobile plants in Canada and the United Kingdom (n=2,600+) indicated that implementation of lean production methods has been uneven across companies and countries and is not associated with greater employee involvement or control. Variations may reflect company-specific responses to the pressures of international competition.…

The Coffee Project Revisited: Teaching Research Skills to Forensic Chemists

ERIC Educational Resources Information Center

Hamnett, Hilary J.; Korb, Ann-Sophie

2017-01-01

This study describes a new module design for teaching research skills to analytical chemists based on the use of a student-led, in-class experiment involving coffee. The module was redesigned in response to feedback from students, and aims to give them the skills they need to be productive in future research projects both within the institution…

Heat-induced accumulation of protein synthesis elongation factor 1A indicates an important role in heat tolerance in potato

USDA-ARS?s Scientific Manuscript database

Heat stress substantially reduces crop productivity worldwide, and will become more severe due to global warming. Identification of proteins involved in heat stress response may help develop varieties for heat tolerance. Eukaryotic elongation factor 1A (eEF1A) is a cytosolic, multifunctional protei...

Antibody response against Betaferon® in immune tolerant mice: involvement of marginal zone B-cells and CD4+ T-cells and apparent lack of immunological memory.

PubMed

Sauerborn, Melody; van Beers, Miranda M C; Jiskoot, Wim; Kijanka, Grzegorz M; Boon, Louis; Schellekens, Huub; Brinks, Vera

2013-01-01

The immunological processes underlying immunogenicity of recombinant human therapeutics are poorly understood. Using an immune tolerant mouse model we previously demonstrated that aggregates are a major trigger of the antidrug antibody (ADA) response against recombinant human interferon beta (rhIFNβ) products including Betaferon®, and that immunological memory seems to be lacking after a rechallenge with non-aggregated rhIFNβ. The apparent absence of immunological memory indicates a CD4+ T-cell independent (Tind) immune response underlying ADA formation against Betaferon®. This hypothesis was tested. Using the immune tolerant mouse model we first validated that rechallenge with highly aggregated rhIFNβ (Betaferon®) does not lead to a subsequent fast increase in ADA titers, suggesting a lack of immunological memory. Next we assessed whether Betaferon® could act as Tind antigen by inactivation of marginal zone (MZ) B-cells during treatment. MZ B-cells are major effector cells involved in a Tind immune response. In a following experiment we depleted the mice from CD4+ T-cells to test their involvement in the ADA response against Betaferon®. Inactivation of MZ B-cells at the start of Betaferon® treatment drastically lowered ADA levels, suggesting a Tind immune response. However, persistent depletion of CD4+ T-cells before and during Betaferon® treatment abolished the ADA response in almost all mice. The immune response against rhIFNβ in immune tolerant mice is neither a T-cell independent nor a classical T-cell dependent immune response. Further studies are needed to confirm absence of immunological memory (cells).

[Participation of final products of lipid peroxidation in the anticancer mechanism of ionizing radiation and radiomimetic cytostatics].

PubMed

Przybyszewski, W M

2001-01-01

This review reports the evidence for the participation of final products of lipid peroxidation in the anticancer mechanism of ionising radiation and radiomimetic cytostatics. Processes of lipid peroxidation occur endogenously in response to oxidative stress and great diversity of reactive metabolites is formed. However, direct observation of radical reaction in pathophysiology of cells, tissues and organs is limited technically. Most investigations focused on the indirect assessment of their final products, aldehydes. The peroxidative breakdown of polyunsaturated fatty acids is believed to be involved in the regulation of cell division, and antitumor effect through biochemical and genetic processes.

CAT--the new committee for advanced therapies at the European Medicines Agency.

PubMed

Celis, P

2010-01-01

The Regulation on Advanced Therapies (Regulation (EC) 1394/2007) establishes a new scientific committee, the Committee for Advanced Therapies (CAT), at the European Medicines Agency. The CAT is composed of experts in the field of Advanced Therapy Medicinal Products (ATMPs)--gene and cell therapy and tissue engineered products--and is responsible for the evaluation of the marketing authorisation applications for this novel class of products. The CAT is also involved in all scientific advice on ATMPs and in two new regulatory procedures for ATMPs, the classification and the certification procedures. The CAT will also play a key role in early contacts with developers of ATMPs.

Memory T cell proliferative responses and IFN-γ productivity sustain long-lasting efficacy of a Cap-based PCV2 vaccine upon PCV2 natural infection and associated disease.

PubMed

Ferrari, Luca; Borghetti, Paolo; De Angelis, Elena; Martelli, Paolo

2014-04-16

Porcine circovirus type 2 (PCV2) vaccination represents an important measure to cope with PCV2 infection; however, data regarding the modulation of the immune cell compartment are still limited, especially under field conditions. This study is aimed at investigating the features of the cellular immune response in conventional piglets induced by vaccination using a capsid (Cap) protein-based PCV2 vaccine compared to unvaccinated animals when exposed to PCV2 natural infection. Immune reactivity was evaluated by quantifying peripheral cell subsets involved in the anti-viral response and characterizing the interferon-gamma (IFN-γ) secreting cell (SC) responsiveness both in vivo and upon in vitro whole PCV2 recall. The vaccination triggered an early and intense IFN-γ secreting cell response and induced the activation of peripheral lymphocytes. The early increase of IFN-γ SC frequencies resulted in a remarkable and transient tendency to increased IFN-γ productivity in vaccinated pigs. In vaccinated animals, soon before the onset of infection occurred 15-16 weeks post-vaccination, the recalled PCV2-specific immune response was characterized by moderate PCV2-specific IFN-γ secreting cell frequencies and augmented productivity together with reactive CD4+CD8+ memory T cells. Conversely, upon infection, unvaccinated animals showed very high frequencies of IFN-γ secreting cells and a tendency to lower productivity, which paralleled with effector CD4-CD8+ cytotoxic cell responsiveness. The study shows that PCV2 vaccination induces a long-lasting immunity sustained by memory T cells and IFN-γ secreting cells that potentially played a role in preventing the onset of infection; the extent and duration of this reactivity can be an important feature for evaluating the protective immunity induced by vaccination.

Appearance Matters: Neural Correlates of Food Choice and Packaging Aesthetics

PubMed Central

Van der Laan, Laura N.; De Ridder, Denise T. D.; Viergever, Max A.; Smeets, Paul A. M.

2012-01-01

Neuro-imaging holds great potential for predicting choice behavior from brain responses. In this study we used both traditional mass-univariate and state-of-the-art multivariate pattern analysis to establish which brain regions respond to preferred packages and to what extent neural activation patterns can predict realistic low-involvement consumer choices. More specifically, this was assessed in the context of package-induced binary food choices. Mass-univariate analyses showed that several regions, among which the bilateral striatum, were more strongly activated in response to preferred food packages. Food choices could be predicted with an accuracy of up to 61.2% by activation patterns in brain regions previously found to be involved in healthy food choices (superior frontal gyrus) and visual processing (middle occipital gyrus). In conclusion, this study shows that mass-univariate analysis can detect small package-induced differences in product preference and that MVPA can successfully predict realistic low-involvement consumer choices from functional MRI data. PMID:22848586

Jasmonic Acid, Abscisic Acid, and Salicylic Acid Are Involved in the Phytoalexin Responses of Rice to Fusarium fujikuroi, a High Gibberellin Producer Pathogen.

PubMed

Siciliano, Ilenia; Amaral Carneiro, Greice; Spadaro, Davide; Garibaldi, Angelo; Gullino, Maria Lodovica

2015-09-23

Fusarium fujikuroi, the causal agent of bakanae disease, is the main seedborne pathogen on rice. To understand the basis of rice resistance, a quantitative method to simultaneously detect phytohormones and phytoalexins was developed by using HPLC-MS/MS. With this method dynamic profiles and possible interactions of defense-related phytohormones and phytoalexins were investigated on two rice cultivars, inoculated or not with F. fujikuroi. In the resistant cultivar Selenio, the presence of pathogen induced high production of phytoalexins, mainly sakuranetin, and symptoms of bakanae were not observed. On the contrary, in the susceptible genotype Dorella, the pathogen induced the production of gibberellin and abscisic acid and inhibited jasmonic acid production, phytoalexins were very low, and bakanae symptoms were observed. The results suggested that a wide range of secondary metabolites are involved in plant defense against pathogens and phytoalexin synthesis could be an important factor for rice resistance against bakanae disease.

Hydrogen peroxide - production, fate and role in redox signaling of tumor cells.

PubMed

Lennicke, Claudia; Rahn, Jette; Lichtenfels, Rudolf; Wessjohann, Ludger A; Seliger, Barbara

2015-09-14

Hydrogen peroxide (H2O2) is involved in various signal transduction pathways and cell fate decisions. The mechanism of the so called "redox signaling" includes the H2O2-mediated reversible oxidation of redox sensitive cysteine residues in enzymes and transcription factors thereby altering their activities. Depending on its intracellular concentration and localization, H2O2 exhibits either pro- or anti-apoptotic activities. In comparison to normal cells, cancer cells are characterized by an increased H2O2 production rate and an impaired redox balance thereby affecting the microenvironment as well as the anti-tumoral immune response. This article reviews the current knowledge about the intracellular production of H2O2 along with redox signaling pathways mediating either the growth or apoptosis of tumor cells. In addition it will be discussed how the targeting of H2O2-linked sources and/or signaling components involved in tumor progression and survival might lead to novel therapeutic targets.

Biomphalaria glabrata transcriptome: cDNA microarray profiling identifies resistant- and susceptible-specific gene expression in haemocytes from snail strains exposed to Schistosoma mansoni

PubMed Central

Lockyer, Anne E; Spinks, Jenny; Kane, Richard A; Hoffmann, Karl F; Fitzpatrick, Jennifer M; Rollinson, David; Noble, Leslie R; Jones, Catherine S

2008-01-01

Background Biomphalaria glabrata is an intermediate snail host for Schistosoma mansoni, one of the important schistosomes infecting man. B. glabrata/S. mansoni provides a useful model system for investigating the intimate interactions between host and parasite. Examining differential gene expression between S. mansoni-exposed schistosome-resistant and susceptible snail lines will identify genes and pathways that may be involved in snail defences. Results We have developed a 2053 element cDNA microarray for B. glabrata containing clones from ORESTES (Open Reading frame ESTs) libraries, suppression subtractive hybridization (SSH) libraries and clones identified in previous expression studies. Snail haemocyte RNA, extracted from parasite-challenged resistant and susceptible snails, 2 to 24 h post-exposure to S. mansoni, was hybridized to the custom made cDNA microarray and 98 differentially expressed genes or gene clusters were identified, 94 resistant-associated and 4 susceptible-associated. Quantitative PCR analysis verified the cDNA microarray results for representative transcripts. Differentially expressed genes were annotated and clustered using gene ontology (GO) terminology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. 61% of the identified differentially expressed genes have no known function including the 4 susceptible strain-specific transcripts. Resistant strain-specific expression of genes implicated in innate immunity of invertebrates was identified, including hydrolytic enzymes such as cathepsin L, a cysteine proteinase involved in lysis of phagocytosed particles; metabolic enzymes such as ornithine decarboxylase, the rate-limiting enzyme in the production of polyamines, important in inflammation and infection processes, as well as scavenging damaging free radicals produced during production of reactive oxygen species; stress response genes such as HSP70; proteins involved in signalling, such as importin 7 and copine 1, cytoplasmic intermediate filament (IF) protein and transcription enzymes such as elongation factor 1α and EF-2. Conclusion Production of the first cDNA microarray for profiling gene expression in B. glabrata provides a foundation for expanding our understanding of pathways and genes involved in the snail internal defence system (IDS). We demonstrate resistant strain-specific expression of genes potentially associated with the snail IDS, ranging from signalling and inflammation responses through to lysis of proteinacous products (encapsulated sporocysts or phagocytosed parasite components) and processing/degradation of these targeted products by ubiquitination. PMID:19114004

Biomphalaria glabrata transcriptome: cDNA microarray profiling identifies resistant- and susceptible-specific gene expression in haemocytes from snail strains exposed to Schistosoma mansoni.

PubMed

Lockyer, Anne E; Spinks, Jenny; Kane, Richard A; Hoffmann, Karl F; Fitzpatrick, Jennifer M; Rollinson, David; Noble, Leslie R; Jones, Catherine S

2008-12-29

Biomphalaria glabrata is an intermediate snail host for Schistosoma mansoni, one of the important schistosomes infecting man. B. glabrata/S. mansoni provides a useful model system for investigating the intimate interactions between host and parasite. Examining differential gene expression between S. mansoni-exposed schistosome-resistant and susceptible snail lines will identify genes and pathways that may be involved in snail defences. We have developed a 2053 element cDNA microarray for B. glabrata containing clones from ORESTES (Open Reading frame ESTs) libraries, suppression subtractive hybridization (SSH) libraries and clones identified in previous expression studies. Snail haemocyte RNA, extracted from parasite-challenged resistant and susceptible snails, 2 to 24 h post-exposure to S. mansoni, was hybridized to the custom made cDNA microarray and 98 differentially expressed genes or gene clusters were identified, 94 resistant-associated and 4 susceptible-associated. Quantitative PCR analysis verified the cDNA microarray results for representative transcripts. Differentially expressed genes were annotated and clustered using gene ontology (GO) terminology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. 61% of the identified differentially expressed genes have no known function including the 4 susceptible strain-specific transcripts. Resistant strain-specific expression of genes implicated in innate immunity of invertebrates was identified, including hydrolytic enzymes such as cathepsin L, a cysteine proteinase involved in lysis of phagocytosed particles; metabolic enzymes such as ornithine decarboxylase, the rate-limiting enzyme in the production of polyamines, important in inflammation and infection processes, as well as scavenging damaging free radicals produced during production of reactive oxygen species; stress response genes such as HSP70; proteins involved in signalling, such as importin 7 and copine 1, cytoplasmic intermediate filament (IF) protein and transcription enzymes such as elongation factor 1alpha and EF-2. Production of the first cDNA microarray for profiling gene expression in B. glabrata provides a foundation for expanding our understanding of pathways and genes involved in the snail internal defence system (IDS). We demonstrate resistant strain-specific expression of genes potentially associated with the snail IDS, ranging from signalling and inflammation responses through to lysis of proteinacous products (encapsulated sporocysts or phagocytosed parasite components) and processing/degradation of these targeted products by ubiquitination.

Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone

PubMed Central

Chuang, Ting-Yun; Cheng, An-Jie; Chen, I-Ting; Lan, Tien-Yun; Huang, I-Hsuan; Shiau, Chung-Wai; Hsu, Chia-Lin; Liu, Ya-Wen; Chang, Zee-Fen; Tseng, Ping-Hui; Kuo, Jean-Cheng

2017-01-01

The innate immune response is a central process that is activated during pathogenic infection in order to maintain physiological homeostasis. It is well known that dexamethasone (Dex), a synthetic glucocorticoid, is a potent immunosuppressant that inhibits the cytokine production induced by bacterial lipopolysaccharides (LPS). Nevertheless, the extent to which the functional groups of Dex control the excessive activation of inflammatory reactions remains unknown. Furthermore, importantly, the role of Dex in the innate immune response remains unclear. Here we explore the mechanism of LPS-induced TNF-α secretion and reveal p38 MAPK signaling as a target of Dex that is involved in control of tumor necrosis factor-α (TNF-α)-converting enzyme (TACE) activity; that later mediates the shedding of TNF-α that allows its secretion. We further demonstrate that the 11-hydroxyl and 21-hydroxyl groups of Dex are the main groups that are involved in reducing LPS-induced TNF-α secretion by activated macrophages. Blockage of the hydroxyl groups of Dex inhibits immunosuppressant effect of Dex during LPS-induced TNF-α secretion and mouse mortality. Our findings demonstrate Dex signaling is involved in the control of innate immunity. PMID:28537905

EOSINOPHILS: MULTIFACETED BIOLOGIC PROPERTIES AND ROLES IN HEALTH AND DISEASE

PubMed Central

Kita, Hirohito

2011-01-01

Summary Eosinophils are leukocytes resident in mucosal tissues. During Th2-type inflammation, eosinophils are recruited from bone marrow and blood to the sites of immune response. While eosinophils have been considered end-stage cells involved in host protection against parasite infection and immunopathology in hypersensitivity disease, recent studies changed this perspective. Eosinophils are now considered multifunctional leukocytes involved in tissue homeostasis, modulation of adaptive immune responses, and innate immunity to certain microbes. Eosinophils are capable of producing immunoregulatory cytokines and are actively involved in regulation of Th2-type immune responses. However, such new information does not preclude earlier observations showing that eosinophils, in particular human eosinophils, are also effector cells with pro-inflammatory and destructive capabilities. Eosinophils with activation phenotypes are observed in biological specimens from patients with disease, and deposition of eosinophil products is readily seen in the affected tissues from these patients. Therefore, it would be reasonable to consider the eosinophil a multifaceted leukocyte that contributes to various physiological and pathological processes depending on their location and activation status. This review summarizes the emerging concept of the multifaceted immunobiology of eosinophils and discusses the roles of eosinophils in health and disease and the challenges and perspectives in the field. PMID:21682744

The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection

PubMed Central

2013-01-01

Background Chlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. This study aimed to investigate the role of primary human cellular responses to chlamydial stress response proteases and chlamydial infection to further identify the immune processes involved in serious disease sequelae. Results Laboratory cell cultures and primary human reproductive epithelial cultures produced IL-6 in response to chlamydial stress response proteases (CtHtrA and CtTsp), UV inactivated Chlamydia, and live Chlamydia. The magnitude of the IL-6 response varied considerably (up to 1000 pg ml-1) across different primary human reproductive cultures. Thus different levels of IL-6 production by reproductive epithelia may be a determinant in disease outcome. Interestingly, co-culture models with either THP-1 cells or autologous primary human PBMC generally resulted in increased levels of IL-6, except in the case of live Chlamydia where the level of IL-6 was decreased compared to the epithelial cell culture only, suggesting this pathway may be able to be modulated by live Chlamydia. PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts. Therefore, these proteases may possess conserved innate PAMPs. MAP kinases appeared to be involved in this IL-6 induction from human cells. Finally, we also demonstrated that IL-6 was induced by these proteins and Chlamydia from mouse primary reproductive cell cultures (BALB/C mice) and mouse laboratory cell models. Conclusions We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism. PMID:24238294

Monocyte-derived dendritic cells exposed to Der p 1 allergen enhance the recruitment of Th2 cells: major involvement of the chemokines TARC/CCL17 and MDC/CCL22.

PubMed

Hammad, Hamida; Smits, Hermelijn H; Ratajczak, Céline; Nithiananthan, Asokananthan; Wierenga, Eddy A; Stewart, Geoffrey A; Jacquet, Alain; Tonnel, Andre-Bernard; Pestel, Joël

2003-01-01

Dendritic cells (DC) are potent antigen - presenting cells that can orientate the immune response towards a Th1 or a Th2 type. DC produce chemokines that are involved in the recruitment of either Th1 cells, such as IP10 (CXCL10), Th2 cells such as TARC (CCL17) and MDC (CCL22), or non-polarized T cells such as RANTES (CCL5) and MIP-lalpha (CCL3). We investigated whether monocyte-derived DC (MD-DC) generated from healthy donors or from patients sensitive to Dermatophagoides pteronyssinus (Dpt) and exposed to the cysteine-protease Der p 1(allergen of Dpt), could upregulate the expression of chemokines involved in type 1 or type 2 T cell recruitment. MD-DC were pulsed with either Der p 1 or with LPS as the control and the chemokines produced were evaluated using ELISA and chemotaxis assays. Der p 1-pulsed DC from allergic patients showed increased TARC (CCL17) and MDC (CCL22) production without modifying IP-10 (CXCL10) release. Der p 1-pulsed DC from healthy donors showed only increased IP-10 (CXCL10) secretion. RANTES (CCL5) and MIP-lalpha (CCL3) production were similarly increased when DC were from healthy or allergic donors. The selective Th2 clone recruitment activity of supernatants from Der p 1-pulsed DC of allergic patients was inhibited by anti-TARC (CCL17) and anti-MDC (CCL22) neutralizing Abs. By using anti-IP10 (CXCL10) blocking Abs, supernatants of Der p 1-pulsed DC from healthy donors were shown to be involved in the recruitment of Th1 cells. These results suggest that in allergic patients exposed to house dust mites, DC may favour the exacerbation of the Th2 response via the increase in type 2 chemokine production. Copyright John Libbey Eurotext 2003.

Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells

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

Matsuzaki, Shinichi; Ishizuka, Tamotsu, E-mail: tamotsui@showa.gunma-u.ac.jp; Yamada, Hidenori

Highlights: {yields} The involvement of extracellular acidification in airway remodeling was investigated. {yields} Extracellular acidification alone induced CTGF production in human ASMCs. {yields} Extracellular acidification enhanced TGF-{beta}-induced CTGF production in human ASMCs. {yields} Proton-sensing receptor OGR1 was involved in acidic pH-stimulated CTGF production. {yields} OGR1 may play an important role in airway remodeling in asthma. -- Abstract: Asthma is characterized by airway inflammation, hyper-responsiveness and remodeling. Extracellular acidification is known to be associated with severe asthma; however, the role of extracellular acidification in airway remodeling remains elusive. In the present study, the effects of acidification on the expression of connectivemore » tissue growth factor (CTGF), a critical factor involved in the formation of extracellular matrix proteins and hence airway remodeling, were examined in human airway smooth muscle cells (ASMCs). Acidic pH alone induced a substantial production of CTGF, and enhanced transforming growth factor (TGF)-{beta}-induced CTGF mRNA and protein expression. The extracellular acidic pH-induced effects were inhibited by knockdown of a proton-sensing ovarian cancer G-protein-coupled receptor (OGR1) with its specific small interfering RNA and by addition of the G{sub q/11} protein-specific inhibitor, YM-254890, or the inositol-1,4,5-trisphosphate (IP{sub 3}) receptor antagonist, 2-APB. In conclusion, extracellular acidification induces CTGF production through the OGR1/G{sub q/11} protein and inositol-1,4,5-trisphosphate-induced Ca{sup 2+} mobilization in human ASMCs.« less

Representing Extremes in Agricultural Models

NASA Technical Reports Server (NTRS)

Ruane, Alex

2015-01-01

AgMIP and related projects are conducting several activities to understand and improve crop model response to extreme events. This involves crop model studies as well as the generation of climate datasets and scenarios more capable of capturing extremes. Models are typically less responsive to extreme events than we observe, and miss several forms of extreme events. Models also can capture interactive effects between climate change and climate extremes. Additional work is needed to understand response of markets and economic systems to food shocks. AgMIP is planning a Coordinated Global and Regional Assessment of Climate Change Impacts on Agricultural Production and Food Security with an aim to inform the IPCC Sixth Assessment Report.

Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine Kinases in Human Neutrophils

PubMed Central

Ear, Thornin; Tatsiy, Olga; Allard, Frédérick L.

2017-01-01

Neutrophils play a critical role in innate immunity and also influence adaptive immune responses. This occurs in good part through their production of inflammatory and immunomodulatory cytokines, in conjunction with their prolonged survival at inflamed foci. While a picture of the signaling machinery underlying these neutrophil responses is now emerging, much remains to be uncovered. In this study, we report that neutrophils constitutively express various Src family isoforms (STKs), as well as Syk, and that inhibition of these protein tyrosine kinases selectively hinders inflammatory cytokine generation by acting posttranscriptionally. Accordingly, STK or Syk inhibition decreases the phosphorylation of signaling intermediates (e.g., eIF-4E, S6K, and MNK1) involved in translational control. By contrast, delayed apoptosis appears to be independent of either STKs or Syk. Our data therefore significantly extend our understanding of which neutrophil responses are governed by STKs and Syk and pinpoint some signaling intermediates that are likely involved. In view of the foremost role of neutrophils in several chronic inflammatory conditions, our findings identify potential molecular targets that could be exploited for future therapeutic intervention. PMID:28512645

A Systematic Review of Known Mechanisms of Hydroxyurea-induced Foetal Haemoglobin for Treatment of Sickle Cell Disease

PubMed Central

Pule, Gift D.; Mowla, Shaheen; Novitzky, Nicolas; Wiysonge, Charles S.; Wonkam, Ambroise

2016-01-01

Aims To report on molecular mechanisms of foetal haemoglobin (HbF) induction by hydroxyurea (HU) for the treatment of Sickle Cell Disease (SCD). Study Design Systematic review. Results Studies have provided consistent associations between genomic variations in HbF-promoting loci and variable HbF level in response to HU. Numerous signal transduction pathways have been implicated, through the identification of key genomic variants in BCL11A, HBS1L-MYB, SAR1 or XmnI polymorphism that predispose the response to the treatment, and signal transduction pathways, that modulate γ-globin expression (cAMP/cGMP; Giα/JNK/Jun; methylation and microRNA). Three main molecular pathways have been reported: 1) Epigenetic modifications, transcriptional events and signalling pathways involved in HU-mediated response, 2) Signalling pathways involving HU-mediated response and 3) Post-transcriptional pathways (regulation by microRNAs). Conclusions The complete picture of HU-mediated mechanisms of HbF production in SCD remains elusive. Research on post-transcriptional mechanisms could lead to therapeutic targets that may minimize alterations to the cellular transcriptome. PMID:26327494

A systematic review of known mechanisms of hydroxyurea-induced fetal hemoglobin for treatment of sickle cell disease.

PubMed

Pule, Gift D; Mowla, Shaheen; Novitzky, Nicolas; Wiysonge, Charles S; Wonkam, Ambroise

2015-10-01

To report on molecular mechanisms of fetal hemoglobin (HbF) induction by hydroxyurea (HU) for the treatment of sickle cell disease. Systematic review. Studies have provided consistent associations between genomic variations in HbF-promoting loci and variable HbF level in response to HU. Numerous signal transduction pathways have been implicated, through the identification of key genomic variants in BCL11A, HBS1L-MYB, SAR1 or XmnI polymorphism that predispose the response to the treatment, and signal transduction pathways that modulate γ-globin expression (cAMP/cGMP; Giα/c-Jun N-terminal kinase/Jun; methylation and miRNA). Three main molecular pathways have been reported: i) Epigenetic modifications, transcriptional events and signaling pathways involved in HU-mediated response, ii) Signaling pathways involving HU-mediated response and iii) Post-transcriptional pathways (regulation by miRNAs). The complete picture of HU-mediated mechanisms of HbF production in Sickle Cell Disease remains elusive. Research on post-transcriptional mechanisms could lead to therapeutic targets that may minimize alterations to the cellular transcriptome.

The nature and molecular basis of cutaneous photosensitivity reactions to psoralens and coal tar

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

Pathak, M.A.; Joshi, P.C.

1983-06-01

The basic aspects of cutaneous photosensitization reactions and the mode of therapeutic effectiveness of psoralens and coal tar, the two groups of photosensitizing agents used extensively in the photochemotherapy of psoriasis, have been reviewed. Psoralen-induced skin photosensitization and the therapeutic action of psoralens involve two distinct types of reactions, and these two reactions occur independently of each other and concurrently when the psoralen-treated skin (oral or topical) is exposed to 320 to 400 nm of radiation. The first, type I, is an oxygen-independent reaction and primarily involves photoreaction with DNA; the second, type II, is a sensitized reaction dependent onmore » oxygen and involves the formation of singlet oxygen (1O2). The photoreactive form of psoralen is its triplet state, and the sites of reaction are (1) the cell membrane of the epidermal, dermal, and endothelial cells; (2) the cytoplasmic constituents, such as enzymes, RNA, lysosomes, etc.; (3) the cell nuclei (DNA and chromatin); and (4) the sensitized production of 1O2, which is responsible for cell-membrane damage and vasodilation. The major damage would be initiated by a type I reaction and would be seen in the form of nuclear damage to DNA resulting from the interaction of psoralen with DNA and to a lesser extent with RNA. The skin photosensitization response (erythema, edema, membrane damage, etc.) would result from a type II reaction involving the generation of 1O2. Crude coal tar (CCT), widely used in the Goeckerman therapy for psoriasis, also produces type I and type II reactions. The therapeutic and photosensitizing actions of CCT are due to (1) the photoconjugation of the photoreactive ingredients of CCT with DNA, causing interstrand cross-links; and (2) the production of 1O2. CCT is an efficient producer of 1O2, more so than 8-methoxypsoralen, and is responsible for cell-membrane damage and cellular edema.« less

Immunological profiles in alopecia areata.

PubMed

Galbraith, G M; Thiers, B H; Vasily, D B; Fudenberg, H H

1984-02-01

Cell-mediated immunity and auto-immune phenomena were investigated in sixty patients with active alopecia areata of various degrees of severity. Serum auto-antibodies to thyroid antigens were detected in twenty-three patients. Examination of T-lymphocyte populations, lymphocyte DNA synthesis, and lymphokine production in response to mitogen stimulation revealed no differences between the sixty patients and matched healthy control subjects. However, patients with thyroid auto-immunity and/or the presence of alopecia totalis or universalis showed significant reductions in interactive T lymphocytes (recognized by rosette formation with human B lymphoblastoid cells) and diminished production of leukocyte migration inhibition factor in response to stimulation with phytohaemagglutinin. This suggests that immune mechanisms may be involved in the pathogenesis of alopecia areata which is associated with thyroid auto-immunity or which progresses to total hair loss.

Transcriptome response of the foundation plant Spartina alterniflora to the Deepwater Horizon oil spill.

PubMed

Alvarez, Mariano; Ferreira de Carvalho, Julie; Salmon, Armel; Ainouche, Malika L; Cavé-Radet, Armand; El Amrani, Abdelhak; Foster, Tammy E; Moyer, Sydney; Richards, Christina L

2018-06-04

Despite the severe impacts of the Deepwater Horizon oil spill, the foundation plant species Spartina alterniflora proved resilient to heavy oiling, providing an opportunity to identify mechanisms of response to the anthropogenic stress of crude oil exposure. We assessed plants from oil-affected and unaffected populations using a custom DNA microarray to identify genomewide transcription patterns and gene expression networks that respond to crude oil exposure. In addition, we used T-DNA insertion lines of the model grass Brachypodium distachyon to assess the contribution of four novel candidate genes to crude oil response. Responses in S. alterniflora to hydrocarbon exposure across the transcriptome as well as xenobiotic specific response pathways had little overlap with those previously identified in the model plant Arabidopsis thaliana. Among T-DNA insertion lines of B. distachyon, we found additional support for two candidate genes, one (ATTPS21) involved in volatile production, and the other (SUVH5) involved in epigenetic regulation of gene expression, that may be important in the response to crude oil. The architecture of crude oil response in S. alterniflora is unique from that of the model species A. thaliana, suggesting that xenobiotic response may be highly variable across plant species. In addition, further investigations of regulatory networks may benefit from more information about epigenetic response pathways. © 2018 John Wiley & Sons Ltd.

Beta- Lactam Antibiotics Stimulate Biofilm Formation in Non-Typeable Haemophilus influenzae by Up-Regulating Carbohydrate Metabolism

PubMed Central

Wu, Siva; Li, Xiaojin; Gunawardana, Manjula; Maguire, Kathleen; Guerrero-Given, Debbie; Schaudinn, Christoph; Wang, Charles; Baum, Marc M.; Webster, Paul

2014-01-01

Non-typeable Haemophilus influenzae (NTHi) is a common acute otitis media pathogen, with an incidence that is increased by previous antibiotic treatment. NTHi is also an emerging causative agent of other chronic infections in humans, some linked to morbidity, and all of which impose substantial treatment costs. In this study we explore the possibility that antibiotic exposure may stimulate biofilm formation by NTHi bacteria. We discovered that sub-inhibitory concentrations of beta-lactam antibiotic (i.e., amounts that partially inhibit bacterial growth) stimulated the biofilm-forming ability of NTHi strains, an effect that was strain and antibiotic dependent. When exposed to sub-inhibitory concentrations of beta-lactam antibiotics NTHi strains produced tightly packed biofilms with decreased numbers of culturable bacteria but increased biomass. The ratio of protein per unit weight of biofilm decreased as a result of antibiotic exposure. Antibiotic-stimulated biofilms had altered ultrastructure, and genes involved in glycogen production and transporter function were up regulated in response to antibiotic exposure. Down-regulated genes were linked to multiple metabolic processes but not those involved in stress response. Antibiotic-stimulated biofilm bacteria were more resistant to a lethal dose (10 µg/mL) of cefuroxime. Our results suggest that beta-lactam antibiotic exposure may act as a signaling molecule that promotes transformation into the biofilm phenotype. Loss of viable bacteria, increase in biofilm biomass and decreased protein production coupled with a concomitant up-regulation of genes involved with glycogen production might result in a biofilm of sessile, metabolically inactive bacteria sustained by stored glycogen. These biofilms may protect surviving bacteria from subsequent antibiotic challenges, and act as a reservoir of viable bacteria once antibiotic exposure has ended. PMID:25007395

Comparative genome analysis of Pediococcus damnosus LMG 28219, a strain well-adapted to the beer environment.

PubMed

Snauwaert, Isabel; Stragier, Pieter; De Vuyst, Luc; Vandamme, Peter

2015-04-03

Pediococcus damnosus LMG 28219 is a lactic acid bacterium dominating the maturation phase of Flemish acid beer productions. It proved to be capable of growing in beer, thereby resisting this environment, which is unfavorable for microbial growth. The molecular mechanisms underlying its metabolic capabilities and niche adaptations were unknown up to now. In the present study, whole-genome sequencing and comparative genome analysis were used to investigate this strain's mechanisms to reside in the beer niche, with special focus on not only stress and hop resistances but also folate biosynthesis and exopolysaccharide (EPS) production. The draft genome sequence of P. damnosus LMG 28219 harbored 183 contigs, including an intact prophage region and several coding sequences involved in plasmid replication. The annotation of 2178 coding sequences revealed the presence of many transporters and transcriptional regulators and several genes involved in oxidative stress response, hop resistance, de novo folate biosynthesis, and EPS production. Comparative genome analysis of P. damnosus LMG 28219 with Pediococcus claussenii ATCC BAA-344(T) (beer origin) and Pediococcus pentosaceus ATCC 25745 (plant origin) revealed that various hop resistance genes and genes involved in de novo folate biosynthesis were unique to the strains isolated from beer. This contrasted with the genes related to osmotic stress responses, which were shared between the strains compared. Furthermore, transcriptional regulators were enriched in the genomes of bacteria capable of growth in beer, suggesting that those cause rapid up- or down-regulation of gene expression. Genome sequence analysis of P. damnosus LMG 28219 provided insights into the underlying mechanisms of its adaptation to the beer niche. The results presented will enable analysis of the transcriptome and proteome of P. damnosus LMG 28219, which will result in additional knowledge on its metabolic activities.

Plasma membrane Toll-like receptor activation increases bacterial uptake but abrogates endosomal Lactobacillus acidophilus induction of interferon-β.

PubMed

Boye, Louise; Welsby, Iain; Lund, Lisbeth Drozd; Goriely, Stanislas; Frøkiaer, Hanne

2016-11-01

Lactobacillus acidophilus induces a potent interferon-β (IFN-β) response in dendritic cells (DCs) by a Toll-like receptor 2 (TLR2) -dependent mechanism, in turn leading to strong interleukin-12 (IL-12) production. In the present study, we investigated the involvement of different types of endocytosis in the L. acidophilus-induced IFN-β and IL-12 responses and how TLR2 or TLR4 ligation by lipopolysaccharide and Pam3/4CSK4 influenced endocytosis of L. acidophilus and the induced IFN-β and IL-12 production. Lactobacillus acidophilus was endocytosed by constitutive macropinocytosis taking place in the immature cells as well as by spleen tyrosine kinase (Syk) -dependent phagocytosis but without involvement of plasma membrane TLR2. Stimulation with TLR2 or TLR4 ligands increased macropinocytosis in a Syk-independent manner. As a consequence, incubation of DCs with TLR ligands before incubation with L. acidophilus enhanced the uptake of the bacteria. However, in these experimental conditions, induction of IFN-β and IL-12 was strongly inhibited. As L. acidophilus-induced IFN-β depends on endocytosis and endosomal degradation before signalling and as TLR stimulation from the plasma membrane leading to increased macropinocytosis abrogates IFN-β induction we conclude that plasma membrane TLR stimulation leading to increased macropinocytosis decreases endosomal induction of IFN-β and speculate that this is due to competition between compartments for molecules involved in the signal pathways. In summary, endosomal signalling by L. acidophilus that leads to IFN-β and IL-12 production is inhibited by TLR stimulation from the plasma membrane. © 2016 John Wiley & Sons Ltd.

Transcriptomic analysis of Escherichia coli O157:H7 and K-12 cultures exposed to inorganic and organic acids in stationary phase reveals acidulant- and strain-specific acid tolerance responses.

PubMed

King, Thea; Lucchini, Sacha; Hinton, Jay C D; Gobius, Kari

2010-10-01

The food-borne pathogen Escherichia coli O157:H7 is commonly exposed to organic acid in processed and preserved foods, allowing adaptation and the development of tolerance to pH levels otherwise lethal. Since little is known about the molecular basis of adaptation of E. coli to organic acids, we studied K-12 MG1655 and O157:H7 Sakai during exposure to acetic, lactic, and hydrochloric acid at pH 5.5. This is the first analysis of the pH-dependent transcriptomic response of stationary-phase E. coli. Thirty-four genes and three intergenic regions were upregulated by both strains during exposure to all acids. This universal acid response included genes involved in oxidative, envelope, and cold stress resistance and iron and manganese uptake, as well as 10 genes of unknown function. Acidulant- and strain-specific responses were also revealed. The acidulant-specific response reflects differences in the modes of microbial inactivation, even between weak organic acids. The two strains exhibited similar responses to lactic and hydrochloric acid, while the response to acetic acid was distinct. Acidulant-dependent differences between the strains involved induction of genes involved in the heat shock response, osmoregulation, inorganic ion and nucleotide transport and metabolism, translation, and energy production. E. coli O157:H7-specific acid-inducible genes were identified, suggesting that the enterohemorrhagic E. coli strain possesses additional molecular mechanisms contributing to acid resistance that are absent in K-12. While E. coli K-12 was most resistant to lactic and hydrochloric acid, O157:H7 may have a greater ability to survive in more complex acidic environments, such as those encountered in the host and during food processing.

SpoT-Mediated Regulation and Amino Acid Prototrophy Are Essential for Pyocyanin Production During Parasitic Growth of Pseudomonas aeruginosa in a Co-culture Model System With Aeromonas hydrophila

PubMed Central

Jagmann, Nina; Philipp, Bodo

2018-01-01

The opportunistic pathogen Pseudomonas aeruginosa employs its complex quorum sensing (QS) network to regulate the expression of virulence factors such as pyocyanin. Besides cell density, QS in this bacterium is co-regulated by environmental cues. In this study, we employed a previously established co-culture model system to identify metabolic influences that are involved in the regulation of pyocyanin production in P. aeruginosa. In this co-culture consisting of P. aeruginosa and the chitinolytic bacterium Aeromonas hydrophila, parasitic growth of P. aeruginosa is strictly dependent on the production of pyocyanin. We could show that in this co-culture, pyocyanin production is likely induced by the stringent response mediated by SpoT in response to nutrient limitation. Pyocyanin production by stringent response mutants in the co-culture could not be complemented by overexpression of PqsE. Via transposon mutagenesis, several amino acid auxotrophic mutants were identified that were also unable to produce pyocyanin when PqsE was overexpressed or when complementing amino acids were present. The inability to produce pyocyanin even though PqsE was overexpressed was likely a general effect of amino acid auxotrophy. These results show the value of the co-culture approach to identify both extra- and intracellular metabolic influences on QS that might be important in infection processes as well. PMID:29720972

Nitric oxide contributes to high-salt perception in a blood-sucking insect model.

PubMed

Cano, Agustina; Pontes, Gina; Sfara, Valeria; Anfossi, Diego; Barrozo, Romina B

2017-11-14

In all organisms, salts produce either appetitive or aversive responses depending on the concentration. While low-salt concentration in food elicits positive responses to ingest, high-salt triggers aversion. Still the mechanisms involved in this dual behavior have just started to be uncovered in some organisms. In Rhodnius prolixus, using pharmacological and behavioral assays, we demonstrated that upon high-salt detection in food a nitric oxide (NO) dependent cascade is activated. This activation involves a soluble guanylate cyclase (sGC) and the production of cyclic guanosine monophosphate (cGMP). Thus, appetitive responses to low-salt diets turn to aversion whenever this cascade is activated. Conversely, insects feed over aversive high-salt solutions when it is blocked by reducing NO levels or by affecting the sGC activity. The activation of NO/sGC/cGMP cascade commands the avoidance feeding behavior in R. prolixus. Investigations in other insect species should examine the possibility that high-salt aversion is mediated by NO/sSG/cGMP signaling.

The ALMA Band 3 (84-116 GHz) receiver production plan

NASA Astrophysics Data System (ADS)

Yeung, Keith; Claude, Stéphane; Loop, David

2008-07-01

The NRC Herzberg Institute of Astrophysics (NRC-HIA) is currently responsible to contribute Band 3 (84-116 GHz) receivers to the international ALMA project - a partnership involving North America, Europe and, now, Asia. Not only are the technical requirements for these receivers far more stringent than those for any existing radio astronomy receivers operating at these frequencies, but the delivery schedule for these receivers is equally challenging. Since the Asian partnership joined the ALMA project in 2006, NRC-HIA has been asked to deliver an additional 11 cartridges, for a total of 73 units. Some of these new cartridges will be used for the ALMA Compact Array (ACA) and others as spares. Moreover, the project has also requested that these additional cartridges be delivered in the same time period as the original 62 units. To meet this requirement, production must increase from the existing rate of one unit every four weeks to one every two, taxing the existing production infrastructure at NRC-HIA. Additional test facilities and human resources must be planned to sustain the required production rate over the next several years. Industrial involvement is one of the important elements in our production plan. In order to supplement the existing human resources at NRC-HIA, we are planning to outsource a number of low-risk and labor-intensive tasks to industry. However, NRC-HIA will retain overall project management responsibility and will conduct all the cartridge integration and acceptance test activities in-house. This paper focuses on the resource estimation, planning and project management required to deliver the Band 3 receivers to the ALMA project on time and on budget.

A Roadmap for the Implementation of Continued Process Verification.

PubMed

Boyer, Marcus; Gampfer, Joerg; Zamamiri, Abdel; Payne, Robin

2016-01-01

In 2014, the members of the BioPhorum Operations Group (BPOG) produced a 100-page continued process verification case study, entitled "Continued Process Verification: An Industry Position Paper with Example Protocol". This case study captures the thought processes involved in creating a continued process verification plan for a new product in response to the U.S. Food and Drug Administration's guidance on the subject introduced in 2011. In so doing, it provided the specific example of a plan developed for a new molecular antibody product based on the "A MAb Case Study" that preceded it in 2009.This document provides a roadmap that draws on the content of the continued process verification case study to provide a step-by-step guide in a more accessible form, with reference to a process map of the product life cycle. It could be used as a basis for continued process verification implementation in a number of different scenarios: For a single product and process;For a single site;To assist in the sharing of data monitoring responsibilities among sites;To assist in establishing data monitoring agreements between a customer company and a contract manufacturing organization. The U.S. Food and Drug Administration issued guidance on the management of manufacturing processes designed to improve quality and control of drug products. This involved increased focus on regular monitoring of manufacturing processes, reporting of the results, and the taking of opportunities to improve. The guidance and practice associated with it is known as continued process verification This paper summarizes good practice in responding to continued process verification guidance, gathered from subject matter experts in the biopharmaceutical industry. © PDA, Inc. 2016.

The effects of angiotensin II on blood perfusion in the rat renal papilla

PubMed Central

Walker, L L; Rajaratne, A A J; Blair-West, J R; Harris, P J

1999-01-01

Systemic infusion of angiotensin II (AII) increased papillary blood perfusion (PBP) measured by laser-Doppler flowmetry in rats, aged about 5 weeks. The mechanisms involved in this response were determined by infusion of AII in the presence of systemic doses of losartan (a type 1 AII receptor antagonist), HOE-140 (a bradykinin B2 receptor antagonist), and an inhibitor of NO production - Nω -nitro-L-arginine (NOLA). Mean arterial blood pressure (MAP) and PBP increased in a dose-dependent manner in response to intravenous infusions of AII. Infusion of losartan abolished these responses to AII but HOE-140 was without effect. Infusion of NOLA abolished the increase in PBP but did not affect the pressor response to AII. Systemic infusion of sodium nitroprusside restored the response to AII in experiments with NOLA infusion. The results indicate that the increase in PBP caused by AII is mediated via angiotensin AT1 receptors and does not involve bradykinin B2 receptors. The AII-induced increase in PBP is dependent upon the presence of NO, thus providing a mechanism for maintenance of papillary perfusion in the face of generalized renal vasoconstriction due to AII. PMID:10432357

Involvement of CD28 cosignalling in the T cell-mediated suppression of the IgG antibody response against the TI-2 antigen alpha(1-->3) dextran.

PubMed

Specht, C; Junker, R; Krüger, A; Rademaekers, A; Redlich, H; Kölsch, E

1999-09-01

The humoral immune response against alpha(1-->3) dextran (Dex) in BALB/c mice is characterized by the formation of predominantly IgM antibodies bearing the J558 idiotype. IgG antibodies do not appear in euthymic mice. In athymic animals, however, the response proceeds to a vigorous IgG production. In euthymic mice formation of IgG is suppressed by J558 idiotype specific regulatory T cells recognizing in association with I-Ed and in cognate T/B interaction the V(H) CDR3 derived peptide of the J558 idiotype. Only B-2 lymphocytes produce IgG whereas B-1 cells do not participate in the production of this Ig class. Using novel synthetic all alpha(1-->3)-D-gluco configured tetrasaccharide the Dex-specific B cells can for the first time be analyzed in FACS. In experiments using this newly designed low molecular Dex no signs of B cell apoptosis can be found. This demonstrates a true silencing of persisting Bgamma memory cells as previously suggested by adoptive transfer experiments. In this suppression a further involvement of CD28 and B7-1 interaction can be demonstrated which delivers a necessary costimulatory suppression signal in addition to the cognate TCR/peptide-I-Ed interaction between J558 specific T cells and J558 idiotype bearing B cells.

Proteomic evolution of a wine yeast during the first hours of fermentation.

PubMed

Salvadó, Zoel; Chiva, Rosana; Rodríguez-Vargas, Sonia; Rández-Gil, Francisca; Mas, Albert; Guillamón, José Manuel

2008-11-01

The inoculation of active dry wine yeast (ADWY) is one of the most common practices in winemaking. This inoculation exposes the yeast cells to strong osmotic, acidic and thermal stresses, and adaptation to the new medium is crucial for successful fermentation. We have analysed the changes that occur in the ADWY protein profile in the first hours after inoculation under enological-like conditions at a low temperature. Protein changes mainly included enzymes of the nitrogen and carbon metabolism and proteins related to the cellular stress response. Most of the enzymes of the lower part of the glycolysis showed an increase in their concentration 4 and 24 h after inoculation, indicating an increase in glycolytic flux and in ATP production. However, the shift from respiration to fermentation was not immediate in the inoculation because some mitochondrial proteins involved in oxidative metabolism were induced in the first hours after inoculation. Inoculation in this fresh medium also reduced the cellular concentration of stress proteins produced during industrial production of the ADWY. The only exception was Cys3p, which might be involved in glutathione synthesis as a response to oxidative stress. A better understanding of the yeast stress response to rehydration and inoculation will lead to improvements in the handling efficiency of ADWY in winemaking and presumably to better control of fermentation startup.

Activation of Two Different Resistance Mechanisms in Saccharomyces cerevisiae upon Exposure to Octanoic and Decanoic Acids▿ †

PubMed Central

Legras, J. L.; Erny, C.; Le Jeune, C.; Lollier, M.; Adolphe, Y.; Demuyter, C.; Delobel, P.; Blondin, B.; Karst, F.

2010-01-01

Medium-chain fatty acids (octanoic and decanoic acids) are well known as fermentation inhibitors. During must fermentation, the toxicity of these fatty acids is enhanced by ethanol and low pH, which favors their entrance in the cell, resulting in a decrease of internal pH. We present here the characterization of the mechanisms involved in the establishment of the resistance to these fatty acids. The analysis of the transcriptome response to the exposure to octanoic and decanoic acids revealed that two partially overlapping mechanisms are activated; both responses share many genes with an oxidative stress response, but some key genes were activated differentially. The transcriptome response to octanoic acid stress can be described mainly as a weak acid response, and it involves Pdr12p as the main transporter. The phenotypic analysis of knocked-out strains confirmed the role of the Pdr12p transporter under the control of WAR1 but also revealed the involvement of the Tpo1p major facilitator superfamily proteins (MFS) transporter in octanoic acid expulsion. In contrast, the resistance to decanoic acid is composite. It also involves the transporter Tpo1p and includes the activation of several genes of the beta-oxidation pathway and ethyl ester synthesis. Indeed, the induction of FAA1 and EEB1, coding for a long-chain fatty acyl coenzyme A synthetase and an alcohol acyltransferase, respectively, suggests a detoxification pathway through the production of decanoate ethyl ester. These results are confirmed by the sensitivity of strains bearing deletions for the transcription factors encoded by PDR1, STB5, OAF1, and PIP2 genes. PMID:20851956

Proteomic and enzymatic response under Cr(VI) overload in yeast isolated from textile-dye industry effluent.

PubMed

Irazusta, Verónica; Bernal, Anahí Romina; Estévez, María Cristina; de Figueroa, Lucía I C

2018-02-01

Cyberlindnera jadinii M9 and Wickerhamomyces anomalus M10 isolated from textile-dye liquid effluents has shown capacity for chromium detoxification via Cr(VI) biological reduction. The aim of the study was to evaluate the effect of hexavalent chromium on synthesis of novel and/or specific proteins involved in chromium tolerance and reduction in response to chromium overload in two indigenous yeasts. A study was carried out following a proteomic approach with W. anomalus M10 and Cy. jadinii M9 strains. For this, proteins extracts belonging to total cell extracts, membranes and mitochondria were analyzed. When Cr(VI) was added to culture medium there was an over-synthesis of 39 proteins involved in different metabolic pathways. In both strains, chromium supplementation changed protein biosynthesis by upregulating proteins involved in stress response, methionine metabolism, energy production, protein degradation and novel oxide-reductase enzymes. Moreover, we observed that Cy. jadinii M9 and W. anomalus M10 displayed ability to activate superoxide dismutase, catalase and chromate reductase activity. Two enzymes from the total cell extracts, type II nitroreductase (Frm2) and flavoprotein wrbA (Ycp4), were identified as possibly responsible for inducing crude chromate-reductase activity in cytoplasm of W. anomalus M10 under chromium overload. In Cy.jadinii M9, mitochondrial Ferredoxine-NADP reductase (Yah1) and membrane FAD flavoprotein (Lpd1) were identified as probably involved in Cr(VI) reduction. To our knowledge, this is the first study proposing chromate reductase activity of these four enzymes in yeast and reporting a relationship between protein synthesis, enzymatic response and chromium biospeciation in Cy. jadinii and W. anomalus. Copyright © 2017 Elsevier Inc. All rights reserved.

Nucleotide-oligomerizing domain-1 (NOD1) receptor activation induces pro-inflammatory responses and autophagy in human alveolar macrophages.

PubMed

Juárez, Esmeralda; Carranza, Claudia; Hernández-Sánchez, Fernando; Loyola, Elva; Escobedo, Dante; León-Contreras, Juan Carlos; Hernández-Pando, Rogelio; Torres, Martha; Sada, Eduardo

2014-09-25

Nucleotide-binding oligomerizing domain-1 (NOD1) is a cytoplasmic receptor involved in recognizing bacterial peptidoglycan fragments that localize to the cytosol. NOD1 activation triggers inflammation, antimicrobial mechanisms and autophagy in both epithelial cells and murine macrophages. NOD1 mediates intracellular pathogen clearance in the lungs of mice; however, little is known about NOD1's role in human alveolar macrophages (AMs) or its involvement in Mycobacterium tuberculosis (Mtb) infection. AMs, monocytes (MNs), and monocyte-derived macrophages (MDMs) from healthy subjects were assayed for NOD1 expression. Cells were stimulated with the NOD1 ligand Tri-DAP and cytokine production and autophagy were assessed. Cells were infected with Mtb and treated with Tri-DAP post-infection. CFUs counting determined growth control, and autophagy protein recruitment to pathogen localization sites was analyzed by immunoelectron microscopy. NOD1 was expressed in AMs, MDMs and to a lesser extent MNs. Tri-DAP stimulation induced NOD1 up-regulation and a significant production of IL1β, IL6, IL8, and TNFα in AMs and MDMs; however, the level of NOD1-dependent response in MNs was limited. Autophagy activity determined by expression of proteins Atg9, LC3, IRGM and p62 degradation was induced in a NOD1-dependent manner in AMs and MDMs but not in MNs. Infected AMs could be activated by stimulation with Tri-DAP to control the intracellular growth of Mtb. In addition, recruitment of NOD1 and the autophagy proteins IRGM and LC3 to the Mtb localization site was observed in infected AMs after treatment with Tri-DAP. NOD1 is involved in AM and MDM innate responses, which include proinflammatory cytokines and autophagy, with potential implications in the killing of Mtb in humans.

Ectopic expression of MdSPDS1 in sweet orange (Citrus sinensis Osbeck) reduces canker susceptibility: involvement of H₂O₂ production and transcriptional alteration.

PubMed

Fu, Xing-Zheng; Chen, Chuan-Wu; Wang, Yin; Liu, Ji-Hong; Moriguchi, Takaya

2011-03-28

Enormous work has shown that polyamines are involved in a variety of physiological processes, but information is scarce on the potential of modifying disease response through genetic transformation of a polyamine biosynthetic gene. In the present work, an apple spermidine synthase gene (MdSPDS1) was introduced into sweet orange (Citrus sinensis Osbeck 'Anliucheng') via Agrobacterium-mediated transformation of embryogenic calluses. Two transgenic lines (TG4 and TG9) varied in the transgene expression and cellular endogenous polyamine contents. Pinprick inoculation demonstrated that the transgenic lines were less susceptible to Xanthomonas axonopodis pv. citri (Xac), the causal agent of citrus canker, than the wild type plants (WT). In addition, our data showed that upon Xac attack TG9 had significantly higher free spermine (Spm) and polyamine oxidase (PAO) activity when compared with the WT, concurrent with an apparent hypersensitive response and the accumulation of more H₂O₂. Pretreatment of TG9 leaves with guazatine acetate, an inhibitor of PAO, repressed PAO activity and reduced H₂O₂ accumulation, leading to more conspicuous disease symptoms than the controls when both were challenged with Xac. Moreover, mRNA levels of most of the defense-related genes involved in synthesis of pathogenesis-related protein and jasmonic acid were upregulated in TG9 than in the WT regardless of Xac infection. Our results demonstrated that overexpression of the MdSPDS1 gene prominently lowered the sensitivity of the transgenic plants to canker. This may be, at least partially, correlated with the generation of more H₂O₂ due to increased production of polyamines and enhanced PAO-mediated catabolism, triggering hypersensitive response or activation of defense-related genes.

Ectopic expression of MdSPDS1 in sweet orange (Citrus sinensis Osbeck) reduces canker susceptibility: involvement of H2O2 production and transcriptional alteration

PubMed Central

2011-01-01

Background Enormous work has shown that polyamines are involved in a variety of physiological processes, but information is scarce on the potential of modifying disease response through genetic transformation of a polyamine biosynthetic gene. Results In the present work, an apple spermidine synthase gene (MdSPDS1) was introduced into sweet orange (Citrus sinensis Osbeck 'Anliucheng') via Agrobacterium-mediated transformation of embryogenic calluses. Two transgenic lines (TG4 and TG9) varied in the transgene expression and cellular endogenous polyamine contents. Pinprick inoculation demonstrated that the transgenic lines were less susceptible to Xanthomonas axonopodis pv. citri (Xac), the causal agent of citrus canker, than the wild type plants (WT). In addition, our data showed that upon Xac attack TG9 had significantly higher free spermine (Spm) and polyamine oxidase (PAO) activity when compared with the WT, concurrent with an apparent hypersensitive response and the accumulation of more H2O2. Pretreatment of TG9 leaves with guazatine acetate, an inhibitor of PAO, repressed PAO activity and reduced H2O2 accumulation, leading to more conspicuous disease symptoms than the controls when both were challenged with Xac. Moreover, mRNA levels of most of the defense-related genes involved in synthesis of pathogenesis-related protein and jasmonic acid were upregulated in TG9 than in the WT regardless of Xac infection. Conclusion Our results demonstrated that overexpression of the MdSPDS1 gene prominently lowered the sensitivity of the transgenic plants to canker. This may be, at least partially, correlated with the generation of more H2O2 due to increased production of polyamines and enhanced PAO-mediated catabolism, triggering hypersensitive response or activation of defense-related genes. PMID:21439092

The flavoprotein Tah18-dependent NO synthesis confers high-temperature stress tolerance on yeast cells

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

Nishimura, Akira; Kawahara, Nobuhiro; Takagi, Hiroshi, E-mail: hiro@bs.naist.jp

Highlights: Black-Right-Pointing-Pointer NO is produced from L-arginine in response to elevated temperature in yeast. Black-Right-Pointing-Pointer Tah18 was first identified as the yeast protein involved in NO synthesis. Black-Right-Pointing-Pointer Tah18-dependent NO synthesis confers tolerance to high-temperature on yeast cells. -- Abstract: Nitric oxide (NO) is a ubiquitous signaling molecule involved in the regulation of a large number of cellular functions. In the unicellular eukaryote yeast, NO may be involved in stress response pathways, but its role is poorly understood due to the lack of mammalian NO synthase (NOS) orthologues. Previously, we have proposed the oxidative stress-induced L-arginine synthesis and its physiologicalmore » role under stress conditions in yeast Saccharomyces cerevisiae. Here, our experimental results indicated that increased conversion of L-proline into L-arginine led to NO production in response to elevated temperature. We also showed that the flavoprotein Tah18, which was previously reported to transfer electrons to the Fe-S cluster protein Dre2, was involved in NO synthesis in yeast. Gene knockdown analysis demonstrated that Tah18-dependent NO synthesis confers high-temperature stress tolerance on yeast cells. As it appears that such a unique cell protection mechanism is specific to yeasts and fungi, it represents a promising target for antifungal activity.« less

The FANC pathway is activated by adenovirus infection and promotes viral replication-dependent recombination

PubMed Central

Cherubini, Gioia; Naim, Valeria; Caruso, Paola; Burla, Romina; Bogliolo, Massimo; Cundari, Enrico; Benihoud, Karim; Saggio, Isabella; Rosselli, Filippo

2011-01-01

Deciphering the crosstalk between a host cell and a virus during infection is important not only to better define viral biology but also to improve our understanding of cellular processes. We identified the FANC pathway as a helper of viral replication and recombination by searching for cellular targets that are modified by adenovirus (Ad) infection and are involved in its outcome. This pathway, which is involved in the DNA damage response and checkpoint control, is altered in Fanconi anaemia, a rare cancer predisposition syndrome. We show here that Ad5 infection activates the FANC pathway independent of the classical DNA damage response. Infection with a non-replicating Ad shows that the presence of viral DNA is not sufficient to induce the monoubiquitination of FANCD2 but still activates the DNA damage response coordinated by phospho-NBS1 and phospho-CHK1. E1A expression alone fails to induce FANCD2 monoubiquitination, indicating that a productive viral infection and/or replication is required for FANC pathway activation. Our data indicate that Ad5 infection induces FANCD2 activation to promote its own replication. Specifically, we show that FANCD2 is involved in the recombination process that accompanies viral DNA replication. This study provides evidence of a DNA damage-independent function of the FANC pathway and identifies a cellular system involved in Ad5 recombination. PMID:21421559

From UV to Near-Infrared Light-Responsive Metal-Organic Framework Composites: Plasmon and Upconversion Enhanced Photocatalysis.

PubMed

Li, Dandan; Yu, Shu-Hong; Jiang, Hai-Long

2018-05-15

The exploitation of photocatalysts that harvest solar spectrum as broad as possible remains a high-priority target yet grand challenge. In this work, for the first time, metal-organic framework (MOF) composites are rationally fabricated to achieve broadband spectral response from UV to near-infrared (NIR) region. In the core-shell structured upconversion nanoparticles (UCNPs)-Pt@MOF/Au composites, the MOF is responsive to UV and a bit visible light, the plasmonic Au nanoparticles (NPs) accept visible light, whereas the UCNPs absorb NIR light to emit UV and visible light that are harvested by the MOF and Au once again. Moreover, the MOF not only facilitates the generation of "bare and clean" Au NPs on its surface and realizes the spatial separation for the Au and Pt NPs, but also provides necessary access for catalytic substrates/products to Pt active sites. As a result, the optimized composite exhibits excellent photocatalytic hydrogen production activity (280 µmol g -1 h -1 ) under simulated solar light, and the involved mechanism of photocatalytic H 2 production under UV, visible, and NIR irradiation is elucidated. Reportedly, this is an extremely rare study on photocatalytic H 2 production by light harvesting in all UV, visible, and NIR regions. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria.

PubMed

Bastos, Marcele F; Kayano, Ana Carolina A V; Silva-Filho, João Luiz; Dos-Santos, João Conrado K; Judice, Carla; Blanco, Yara C; Shryock, Nathaniel; Sercundes, Michelle K; Ortolan, Luana S; Francelin, Carolina; Leite, Juliana A; Oliveira, Rafaella; Elias, Rosa M; Câmara, Niels O S; Lopes, Stefanie C P; Albrecht, Letusa; Farias, Alessandro S; Vicente, Cristina P; Werneck, Claudio C; Giorgio, Selma; Verinaud, Liana; Epiphanio, Sabrina; Marinho, Claudio R F; Lalwani, Pritesh; Amino, Rogerio; Aliberti, Julio; Costa, Fabio T M

2018-03-20

Cerebral malaria (CM) is a multifactorial syndrome involving an exacerbated proinflammatory status, endothelial cell activation, coagulopathy, hypoxia, and accumulation of leukocytes and parasites in the brain microvasculature. Despite significant improvements in malaria control, 15% of mortality is still observed in CM cases, and 25% of survivors develop neurologic sequelae for life-even after appropriate antimalarial therapy. A treatment that ameliorates CM clinical signs, resulting in complete healing, is urgently needed. Previously, we showed a hyperbaric oxygen (HBO)-protective effect against experimental CM. Here, we provide molecular evidence that HBO targets brain endothelial cells by decreasing their activation and inhibits parasite and leukocyte accumulation, thus improving cerebral microcirculatory blood flow. HBO treatment increased the expression of aryl hydrocarbon receptor over hypoxia-inducible factor 1-α (HIF-1α), an oxygen-sensitive cytosolic receptor, along with decreased indoleamine 2,3-dioxygenase 1 expression and kynurenine levels. Moreover, ablation of HIF-1α expression in endothelial cells in mice conferred protection against CM and improved survival. We propose that HBO should be pursued as an adjunctive therapy in CM patients to prolong survival and diminish deleterious proinflammatory reaction. Furthermore, our data support the use of HBO in therapeutic strategies to improve outcomes of non-CM disorders affecting the brain.-Bastos, M. F., Kayano, A. C. A. V., Silva-Filho, J. L., Dos-Santos, J. C. K., Judice, C., Blanco, Y. C., Shryock, N., Sercundes, M. K., Ortolan, L. S., Francelin, C., Leite, J. A., Oliveira, R., Elias, R. M., Câmara, N. O. S., Lopes, S. C. P., Albrecht, L., Farias, A. S., Vicente, C. P., Werneck, C. C., Giorgio, S., Verinaud, L., Epiphanio, S., Marinho, C. R. F., Lalwani, P., Amino, R., Aliberti, J., Costa, F. T. M. Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria.

Response to Oil Sands Products Assessment

DTIC Science & Technology

2015-09-01

volume of the spill, its duration, and the viscosity and density of the crude oil involved. The denser components of a Dilbit spill would be difficult...C-4 Figure ‎C-2. Viscosity change for the three types of diluted bitumen. ......................................................... C...specific gravity) approaching or even exceeding the density of water. As a result of their high viscosity , bitumen cannot be produced by conventional

78 FR 14636 - Food Ingredients and Sources of Radiation Listed and Approved for Use in the Production of Meat...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-07

... issues raised in the comments. Comment: A commenter asked why there were no tests involving the human body after eating the substances. Another commenter expressed concern about the cumulative effects of.... Response: FSIS and FDA do not conduct tests of the effects of food ingredients directly on humans. For a...

Matter-antimatter cosmology

NASA Technical Reports Server (NTRS)

Omnes, R.

1973-01-01

Mechanisms responsible for the orgin and separation of matter and antimatter in the universe are discussed. Particular attention was given to coalesence. This mechanism involves annihilation production of along the boundary of matter-antimatter, high energy photons, electrons, and positrons. These particles together with secondary particles which they put into motion by collisions, carry their momentum to the matter or antimatter fluid. Coalescence and annihilation rates are discussed.

Changes in Thermoregulatory Behavior during Microwave Irradiation,

DTIC Science & Technology

Voluntary behavioral action is an organism’s first defense against exogenous thermal challenge. Endotherms and ectotherms alike use behavioral...level. For ectothermic species, these behaviors represent most of the thermoregulatory response available to the organism. For endothermic species, these...involvement of innate mechanisms of heat production and heat loss during thermoregulation , thus conserving the body’s energy stores and water.

Gene–culture coevolution and the nature of human sociality

PubMed Central

Gintis, Herbert

2011-01-01

Human characteristics are the product of gene–culture coevolution, which is an evolutionary dynamic involving the interaction of genes and culture over long time periods. Gene–culture coevolution is a special case of niche construction. Gene–culture coevolution is responsible for human other-regarding preferences, a taste for fairness, the capacity to empathize and salience of morality and character virtues. PMID:21320901

Goal-Directed Behavior and Contextual Factors in the Classroom: An Innovative Approach to the Study of Multiple Goals

ERIC Educational Resources Information Center

Boekaerts, Monique; de Koning, Els; Vedder, Paul

2006-01-01

Principles of social constructivism and about communities of learners clarify that being a responsible student involves performing well on a task as well as having motivation, having volition strategies, understanding rules and regulations, and having access to a productive social support network. A hotly debated issue is what motivation processes…

Systems Biology for Smart Crops and Agricultural Innovation: Filling the Gaps between Genotype and Phenotype for Complex Traits Linked with Robust Agricultural Productivity and Sustainability

PubMed Central

Pathak, Rajesh Kumar; Gupta, Sanjay Mohan; Gaur, Vikram Singh; Pandey, Dinesh

2015-01-01

Abstract In recent years, rapid developments in several omics platforms and next generation sequencing technology have generated a huge amount of biological data about plants. Systems biology aims to develop and use well-organized and efficient algorithms, data structure, visualization, and communication tools for the integration of these biological data with the goal of computational modeling and simulation. It studies crop plant systems by systematically perturbing them, checking the gene, protein, and informational pathway responses; integrating these data; and finally, formulating mathematical models that describe the structure of system and its response to individual perturbations. Consequently, systems biology approaches, such as integrative and predictive ones, hold immense potential in understanding of molecular mechanism of agriculturally important complex traits linked to agricultural productivity. This has led to identification of some key genes and proteins involved in networks of pathways involved in input use efficiency, biotic and abiotic stress resistance, photosynthesis efficiency, root, stem and leaf architecture, and nutrient mobilization. The developments in the above fields have made it possible to design smart crops with superior agronomic traits through genetic manipulation of key candidate genes. PMID:26484978

Trichoderma harzianum enhances tomato indirect defense against aphids.

PubMed

Coppola, Mariangela; Cascone, Pasquale; Chiusano, Maria Luisa; Colantuono, Chiara; Lorito, Matteo; Pennacchio, Francesco; Rao, Rosa; Woo, Sheridan Lois; Guerrieri, Emilio; Digilio, Maria Cristina

2017-12-01

Many fungal root symbionts of the genus Trichoderma are well-known for their beneficial effects on agronomic performance and protection against plant pathogens; moreover, they may enhance protection from insect pests, by triggering plant resistance mechanisms. Defense barriers against insects are induced by the activation of metabolic pathways involved in the production of defense-related plant compounds, either directly active against herbivore insects, or exerting an indirect effect, by increasing the attraction of herbivore natural enemies. In a model system composed of the tomato plant, the aphid Macrosiphum euphorbiae and the parasitoid Aphidius ervi, plant metabolic changes induced by Trichoderma harzianum and their effects on higher trophic levels have been assessed. T. harzianum T22 treatments induce a primed state that upon aphid attacks leads to an increased attraction of aphid parasitoids, mediated by the enhanced production of volatile organic compounds (VOCs) that are known to induce Aphidius ervi flight. Transcriptome sequencing of T22-treated plants infested by aphids showed a remarkable upregulation of genes involved in terpenoids biosynthesis and salicylic acid pathway, which are consistent with the observed flight response of A. ervi and the VOC bouquet profile underlying this behavioral response. © 2017 Institute of Zoology, Chinese Academy of Sciences.

Gene expression profiling of Escherichia coli in response to interactions with the lettuce rhizosphere.

PubMed

Hou, Z; Fink, R C; Black, E P; Sugawara, M; Zhang, Z; Diez-Gonzalez, F; Sadowsky, M J

2012-11-01

The objective of this study was to examine transcriptional changes in Escherichia coli when the bacterium was growing in the lettuce rhizoshpere. A combination of microarray analyses, colonization assays and confocal microscopy was used to gain a more complete understanding of bacterial genes involved in the colonization and growth of E. coli K12 in the lettuce root rhizosphere using a novel hydroponic assay system. After 3 days of interaction with lettuce roots, E. coli genes involved in protein synthesis, stress responses and attachment were up-regulated. Mutants in curli production (crl, csgA) and flagella synthesis (fliN) had a reduced capacity to attach to roots as determined by bacterial counts and by confocal laser scanning microscopy. This study indicates that E. coli K12 has the capability to colonize lettuce roots by using attachment genes and can readily adapt to the rhizosphere of lettuce plants. Results of this study show curli production and biofilm modulation genes are important for rhizosphere colonization and may provide useful targets to disrupt this process. Further studies using pathogenic strains will provide additional information about lettuce-E. coli interactions. © 2012 The Authors Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

Escherichia coli LF82 differentially regulates ROS production and mucin expression in intestinal epithelial T84 cells: implication of NOX1.

PubMed

Elatrech, Imen; Marzaioli, Viviana; Boukemara, Hanane; Bournier, Odile; Neut, Christel; Darfeuille-Michaud, Arlette; Luis, José; Dubuquoy, Laurent; El-Benna, Jamel; My-Chan Dang, Pham; Marie, Jean-Claude

2015-05-01

Increased reactive oxygen species (ROS) production is associated with inflamed ileal lesions in Crohn's disease colonized by pathogenic adherent-invasive Escherichia coli LF82. We investigated whether such ileal bacteria can modulate ROS production by epithelial cells, thus impacting on inflammation and mucin expression. Ileal bacteria from patients with Crohn's disease were incubated with cultured epithelial T84 cells, and ROS production was assayed using the luminol-amplified chemiluminescence method. The gentamicin protection assay was used for bacterial invasion of T84 cell. The expression of NADPH oxidase (NOX) subunits, mucin, and IL-8 was analyzed by quantitative real-time PCR and Western blots. Involvement of NOX and ROS was analyzed using diphenyleneiodonium (DPI) and N-acetylcysteine (NAC). Among different bacteria tested, only LF82 induced an increase of ROS production by T84 cells in a dose-dependent manner. This response was inhibited by DPI and NAC. Heat- or ethanol-attenuated LF82 bacteria and the mutant LF82ΔFimA, which does not express pili type 1 and poorly adheres to epithelial cells, did not induce the oxidative response. The LF82-induced oxidative response coincides with its invasion in T84 cells, and both processes were inhibited by DPI. Also, we observed an increased expression of NOX1 and NOXO1 in response to LF82 bacteria versus the mutant LF82ΔFimA. Furthermore, LF82 inhibited mucin gene expression (MUC2 and MUC5AC) in T84 cells while increasing the chemotactic IL-8 expression, both in a DPI-sensitive manner. Adherent-invasive E. coli LF82 induced ROS production by intestinal NADPH oxidase and altered mucin and IL-8 expression, leading to perpetuation of inflammatory lesions in Crohn's disease.

Systematic analyses of the ultraviolet radiation resistance-associated gene product (UVRAG) protein interactome by tandem affinity purification.

PubMed

Son, Ji-Hye; Hwang, Eurim C; Kim, Joungmok

2016-03-01

Ultraviolet radiation resistance-associated gene product (UVRAG) was originally identified as a protein involved in cellular responses to UV irradiation. Subsequent studies have demonstrated that UVRAG plays as an important role in autophagy, a lysosome-dependent catabolic program, as a part of a pro-autophagy PIK3C3/VPS34 lipid kinase complex. Several recent studies have shown that UVRAG is also involved in autophagy-independent cellular functions, such as DNA repair/stability and vesicular trafficking/fusion. Here, we examined the UVRAG protein interactome to obtain information about its functional network. To this end, we screened UVRAG-interacting proteins using a tandem affinity purification method coupled with MALDI-TOF/MS analysis. Our results demonstrate that UVRAG interacts with various proteins involved in a wide spectrum of cellular functions, including genome stability, protein translational elongation, protein localization (trafficking), vacuole organization, transmembrane transport as well as autophagy. Notably, the interactome list of high-confidence UVRAG-interacting proteins is enriched for proteins involved in the regulation of genome stability. Our systematic UVRAG interactome analysis should provide important clues for understanding a variety of UVRAG functions.

Lipoxygenases and their metabolites in formation of plant stress tolerance.

PubMed

Babenko, L M; Shcherbatiuk, M M; Skaterna, T D; Kosakivska, I V

2017-01-01

The review focuses on the analysis of new information concerning molecular enzymology of lipoxygenases – proteins involved in lipid peroxidation and found in animals and plants. Modern concept of structural features, catalytic characteristics and functions of lipoxygenase family enzymes as well as products of their catalytic activity in plants have been discussed and summarized. Issues of enzyme localization in plant cells and tissues, evolution and distribution of lipoxygenases, involvement in production of signaling substances involved in formation of adaptation response to abiotic and biotic stress factors and in regulation of lipoxygenase signal system activity are highlighted. Participants of the elements signaling of LOX-pathway reception and transduction into genome are considered. Special attention is given to jasmonates, metabolites of the allene oxide synthase branch of the lipoxygenase cascade, because these metabolites have high biological activity, are ubiquitously present in all plant organisms, and are involved in regulation of vitally important processes. Data concerning lipoxygenase phylogeny, possible occurrence of a common predecessor for modern isoforms of the enzyme in pro- and eukaryote have been examined. Some results of our studies that open up possibilities of using the lipoxygenase catalytic activity characteristics as biological markers in plant stress tolerance researches are given.

Global transcriptomic analysis of the response of Corynebacterium glutamicum to ferulic acid.

PubMed

Chen, Can; Pan, Junfeng; Yang, Xiaobing; Xiao, He; Zhang, Yaoling; Si, Meiru; Shen, Xihui; Wang, Yao

2017-03-01

Corynebacterium glutamicum can survive by using ferulic acid as the sole carbon source. In this study, we assessed the response of C. glutamicum to ferulic acid stress by means of a global transcriptional response analysis. The transcriptional data showed that several genes involved in degradation of ferulic acid were affected. Moreover, several genes related to the stress response; protein protection or degradation and DNA repair; replication, transcription and translation; and the cell envelope were differentially expressed. Deletion of the katA or sigE gene in C. glutamicum resulted in a decrease in cell viability under ferulic acid stress. These insights will facilitate further engineering of model industrial strains, with enhanced tolerance to ferulic acid to enable easy production of biofuels from lignocellulose.

Molecular Adaptation Mechanisms Employed by Ethanologenic Bacteria in Response to Lignocellulose-derived Inhibitory Compounds

PubMed Central

Ibraheem, Omodele; Ndimba, Bongani K.

2013-01-01

Current international interest in finding alternative sources of energy to the diminishing supplies of fossil fuels has encouraged research efforts in improving biofuel production technologies. In countries which lack sufficient food, the use of sustainable lignocellulosic feedstocks, for the production of bioethanol, is an attractive option. In the pre-treatment of lignocellulosic feedstocks for ethanol production, various chemicals and/or enzymatic processes are employed. These methods generally result in a range of fermentable sugars, which are subjected to microbial fermentation and distillation to produce bioethanol. However, these methods also produce compounds that are inhibitory to the microbial fermentation process. These compounds include products of sugar dehydration and lignin depolymerisation, such as organic acids, derivatised furaldehydes and phenolic acids. These compounds are known to have a severe negative impact on the ethanologenic microorganisms involved in the fermentation process by compromising the integrity of their cell membranes, inhibiting essential enzymes and negatively interact with their DNA/RNA. It is therefore important to understand the molecular mechanisms of these inhibitions, and the mechanisms by which these microorganisms show increased adaptation to such inhibitors. Presented here is a concise overview of the molecular adaptation mechanisms of ethanologenic bacteria in response to lignocellulose-derived inhibitory compounds. These include general stress response and tolerance mechanisms, which are typically those that maintain intracellular pH homeostasis and cell membrane integrity, activation/regulation of global stress responses and inhibitor substrate-specific degradation pathways. We anticipate that understanding these adaptation responses will be essential in the design of 'intelligent' metabolic engineering strategies for the generation of hyper-tolerant fermentation bacteria strains. PMID:23847442

Salicylic Acid-Dependent Plant Stress Signaling via Mitochondrial Succinate Dehydrogenase1[OPEN

PubMed Central

Thatcher, Louise F.

2017-01-01

Mitochondria are known for their role in ATP production and generation of reactive oxygen species, but little is known about the mechanism of their early involvement in plant stress signaling. The role of mitochondrial succinate dehydrogenase (SDH) in salicylic acid (SA) signaling was analyzed using two mutants: disrupted in stress response1 (dsr1), which is a point mutation in SDH1 identified in a loss of SA signaling screen, and a knockdown mutant (sdhaf2) for SDH assembly factor 2 that is required for FAD insertion into SDH1. Both mutants showed strongly decreased SA-inducible stress promoter responses and low SDH maximum capacity compared to wild type, while dsr1 also showed low succinate affinity, low catalytic efficiency, and increased resistance to SDH competitive inhibitors. The SA-induced promoter responses could be partially rescued in sdhaf2, but not in dsr1, by supplementing the plant growth media with succinate. Kinetic characterization showed that low concentrations of either SA or ubiquinone binding site inhibitors increased SDH activity and induced mitochondrial H2O2 production. Both dsr1 and sdhaf2 showed lower rates of SA-dependent H2O2 production in vitro in line with their low SA-dependent stress signaling responses in vivo. This provides quantitative and kinetic evidence that SA acts at or near the ubiquinone binding site of SDH to stimulate activity and contributes to plant stress signaling by increased rates of mitochondrial H2O2 production, leading to part of the SA-dependent transcriptional response in plant cells. PMID:28209841

Effects of nitrous oxide on the production of cytokines and chemokines by the airway epithelium during anesthesia with sevoflurane and propofol.

PubMed

Kumakura, Seiichiro; Yamaguchi, Keisuke; Sugasawa, Yusuke; Murakami, Taisuke; Kikuchi, Toshihiro; Inada, Eiichi; Nagaoka, Isao

2013-12-01

The aim of this study was to evaluate the effects of nitrous oxide (a gaseous anesthetic) on the in vivo production of inflammatory cytokines and chemokines by the airway epithelium, when combined with sevoflurane or propofol. Subjects undergoing simple or segmental mastectomy were randomly assigned to the sevoflurane and nitrous oxide, sevoflurane and air, propofol and nitrous oxide, or propofol and air group (all n=13). Epithelial lining fluid (ELF) was obtained using the bronchoscopic microsampling method prior to and following the mastectomy to enable measurement of the pre- and post-operative levels of certain inflammatory cytokines and chemokines using a cytometric bead array system. Notably, the levels of interleukin (IL)-1β, IL-8 and monocyte chemotactic protein-1 (MCP-1) in the ELF were significantly increased following the operations which involved the inhalation of sevoflurane and nitrous oxide, although the levels of these molecules were not significantly changed by the inhalation of sevoflurane and air. Furthermore, the IL-12p70 levels were significantly reduced in the ELF following the operations that involved the inhalation of sevoflurane and air, although the IL-12p70 levels were not significantly changed by the inhalation of nitrous oxide and sevoflurane. These observations suggest that the combination of sevoflurane and nitrous oxide induces an inflammatory response (increased production of IL-1β, IL-8 and MCP-1) and suppresses the anti-inflammatory response (reduced production of IL-12p70) in the local milieu of the airway. Thus, the combination of these compounds should be carefully administered for anesthesia.

Peroxynitrite mediates testosterone-induced vasodilation of microvascular resistance vessels.

PubMed

Puttabyatappa, Yashoda; Stallone, John N; Ergul, Adviye; El-Remessy, Azza B; Kumar, Sanjiv; Black, Stephen; Johnson, Maribeth; Owen, Mary P; White, Richard E

2013-04-01

Our knowledge of how androgens influence the cardiovascular system is far from complete, and this lack of understanding is especially true of how androgens affect resistance vessels. Our aim was to identify the signaling mechanisms stimulated by testosterone (TES) in microvascular arteries and to understand how these mechanisms mediate TES-induced vasodilation. Mesenteric microvessels were isolated from male Sprague-Dawley rats. Tension studies demonstrated a rapid, concentration-dependent, vasodilatory response to TES that did not involve protein synthesis or aromatization to 17β-estradiol. Dichlorofluorescein fluorescence and nitrotyrosine immunoblot experiments indicated that TES stimulated peroxynitrite formation in microvessels, and functional studies demonstrated that TES-induced vasodilation was inhibited by scavenging peroxynitrite. As predicted, TES enhanced the production of both peroxynitrite precursors (i.e., superoxide and nitic oxide), and xanthine oxidase was identified as the likely source of TES-stimulated superoxide production. Functional and biochemical studies indicated that TES signaling involved activity of the phosphoinositide 3 (PI3) kinase-protein kinase B (Akt) cascade initiated by activation of the androgen receptor and culminated in enhanced production of cGMP and microvascular vasodilation. These findings, derived from a variety of analytical and functional approaches, provide evidence for a novel nongenomic signaling mechanism for androgen action in the microvasculature: TES-stimulated vasodilation mediated primarily by peroxynitrite formed from xanthine oxidase-generated superoxide and NO. This response was associated with activation of the PI3 kinase-Akt signaling cascade initiated by activation of the androgen receptor. We propose this mechanism could account for TES-stimulated cGMP production in microvessels and, ultimately, vasodilation.

Peroxynitrite Mediates Testosterone-Induced Vasodilation of Microvascular Resistance Vessels

PubMed Central

Puttabyatappa, Yashoda; Stallone, John N.; Ergul, Adviye; El-Remessy, Azza B.; Kumar, Sanjiv; Black, Stephen; Johnson, Maribeth; Owen, Mary P.

2013-01-01

Our knowledge of how androgens influence the cardiovascular system is far from complete, and this lack of understanding is especially true of how androgens affect resistance vessels. Our aim was to identify the signaling mechanisms stimulated by testosterone (TES) in microvascular arteries and to understand how these mechanisms mediate TES-induced vasodilation. Mesenteric microvessels were isolated from male Sprague-Dawley rats. Tension studies demonstrated a rapid, concentration-dependent, vasodilatory response to TES that did not involve protein synthesis or aromatization to 17β-estradiol. Dichlorofluorescein fluorescence and nitrotyrosine immunoblot experiments indicated that TES stimulated peroxynitrite formation in microvessels, and functional studies demonstrated that TES-induced vasodilation was inhibited by scavenging peroxynitrite. As predicted, TES enhanced the production of both peroxynitrite precursors (i.e., superoxide and nitic oxide), and xanthine oxidase was identified as the likely source of TES-stimulated superoxide production. Functional and biochemical studies indicated that TES signaling involved activity of the phosphoinositide 3 (PI3) kinase-protein kinase B (Akt) cascade initiated by activation of the androgen receptor and culminated in enhanced production of cGMP and microvascular vasodilation. These findings, derived from a variety of analytical and functional approaches, provide evidence for a novel nongenomic signaling mechanism for androgen action in the microvasculature: TES-stimulated vasodilation mediated primarily by peroxynitrite formed from xanthine oxidase-generated superoxide and NO. This response was associated with activation of the PI3 kinase-Akt signaling cascade initiated by activation of the androgen receptor. We propose this mechanism could account for TES-stimulated cGMP production in microvessels and, ultimately, vasodilation. PMID:23318471

Responses of human cells to ZnO nanoparticles: a gene transcription study†

PubMed Central

Moos, Philip J.; Olszewski, Kyle; Honeggar, Matthew; Cassidy, Pamela; Leachman, Sancy; Woessner, David; Cutler, N. Shane; Veranth, John M.

2013-01-01

The gene transcript profile responses to metal oxide nanoparticles was studied using human cell lines derived from the colon and skin tumors. Much of the research on nanoparticle toxicology has focused on models of inhalation and intact skin exposure, and effects of ingestion exposure and application to diseased skin are relatively unknown. Powders of nominally nanosized SiO2, TiO2, ZnO and Fe2O3 were chosen because these substances are widely used in consumer products. The four oxides were evaluated using colon-derived cell lines, RKO and CaCo-2, and ZnO and TiO2 were evaluated further using skin-derived cell lines HaCaT and SK Mel-28. ZnO induced the most notable gene transcription changes, even though this material was applied at the lowest concentration. Nano-sized and conventional ZnO induced similar responses suggesting common mechanisms of action. The results showed neither a non-specific response pattern common to all substances nor synergy of the particles with TNF-α cotreatment. The response to ZnO was not consistent with a pronounced proinflammatory signature, but involved changes in metal metabolism, chaperonin proteins, and protein folding genes. This response was observed in all cell lines when ZnO was in contact with the human cells. When the cells were exposed to soluble Zn, the genes involved in metal metabolism were induced but the genes involved in protein refoldling were unaffected. This provides some of the first data on the effects of commercial metal oxide nanoparticles on human colon-derived and skin-derived cells. PMID:21769377

Human colonic myocytes are involved in postischemic inflammation through ADAM17-dependent TNFα production

PubMed Central

Jarry, Anne; Bach-Ngohou, Kalyane; Masson, Damien; Dejoie, Thomas; Lehur, Paul-Antoine; Mosnier, Jean-François; Denis, Marc G; Laboisse, Christian L

2005-01-01

The aim of this study was to identify human colonic resident cells able to initiate an inflammatory response in postischemic injury. Postischemic colonic injury, a condition relevant to various clinical settings, involves an inflammatory cascade in intestinal tissues through the recruitment of circulating inflammatory cells. However, there is no information on the nature of resident cells of the different intestinal layers able to initiate a postischemic inflammatory response. It is however an important issue in the context of a pharmacological approach of the early phase of intestinal ischemia. We reasoned that maintaining the different colonic layers as explant cultures in an oxygenated medium immediately after colonic resection, that is, after an ischemic period, would allow one to identify the resident cells able to initiate an inflammatory cascade, without interference of recruited inflammatory/immune cells. To this end, we designed an explant culture system that operationally defines three compartments in surgical specimens of the human colon, based on the microdissected layers, that is, mucosa, submucosa (containing muscularis mucosae) and muscularis propria. To validate the results obtained in explant cultures in the clinical setting of ischemic colitis, eight cases of sigmoid volvulus were examined. Only the myocytes-containing explants produced tumor necrosis factor alpha (TNFα), via an ADAM17 (a disintegrin and metalloproteinase-17)-dependent pathway, as shown by the abrogation of TNFα production by the inhibitor Tapi-2. Immunofluorescence studies identified nonvascular and vascular myocytes as resident cells coexpressing TNFα and ADAM17, both in our postischemic explant system and in surgical specimens from ischemic colitis patients. Finally, time-course experiments on explanted tissues showed that TNFα production by myocytes was an early event triggered by a postischemic oxidative stress involving nuclear factor kappa B (NF-κB). In conclusion, this study identifies human intestinal myocytes as resident cells able to initiate an inflammatory reaction through TNFα production in postischemic conditions, and delineates two points of control in TNFα production, NF-κB and ADAM17, which can be targeted by pharmacological manipulation. PMID:16273118

Involvement of neuronal IL-1β in acquired brain lesions in a rat model of neonatal encephalopathy.

PubMed

Savard, Alexandre; Lavoie, Karine; Brochu, Marie-Elsa; Grbic, Djordje; Lepage, Martin; Gris, Denis; Sebire, Guillaume

2013-09-05

Infection-inflammation combined with hypoxia-ischemia (HI) is the most prevalent pathological scenario involved in perinatal brain damage leading to life-long neurological disabilities. Following lipopolysaccharide (LPS) and/or HI aggression, different patterns of inflammatory responses have been uncovered according to the brain differentiation stage. In fact, LPS pre-exposure has been reported to aggravate HI brain lesions in post-natal day 1 (P1) and P7 rat models that are respectively equivalent - in terms of brain development - to early and late human preterm newborns. However, little is known about the innate immune response in LPS plus HI-induced lesions of the full-term newborn forebrain and the associated neuropathological and neurobehavioral outcomes. An original preclinical rat model has been previously documented for the innate neuroimmune response at different post-natal ages. It was used in the present study to investigate the neuroinflammatory mechanisms that underline neurological impairments after pathogen-induced inflammation and HI in term newborns. LPS and HI exerted a synergistic detrimental effect on rat brain. Their effect led to a peculiar pattern of parasagittal cortical-subcortical infarcts mimicking those in the human full-term newborn with subsequent severe neurodevelopmental impairments. An increased IL-1β response in neocortical and basal gray neurons was demonstrated at 4 h after LPS + HI-exposure and preceded other neuroinflammatory responses such as microglial and astroglial cell activation. Neurological deficits were observed during the acute phase of injury followed by a recovery, then by a delayed onset of profound motor behavior impairment, reminiscent of the delayed clinical onset of motor system impairments observed in humans. Interleukin-1 receptor antagonist (IL-1ra) reduced the extent of brain lesions confirming the involvement of IL-1β response in their pathophysiology. In rat pups at a neurodevelopmental age corresponding to full-term human newborns, a systemic pre-exposure to a pathogen component amplified HI-induced mortality and morbidities that are relevant to human pathology. Neuronal cells were the first cells to produce IL-1β in LPS + HI-exposed full-term brains. Such IL-1β production might be responsible for neuronal self-injuries via well-described neurotoxic mechanisms such as IL-1β-induced nitric oxide production, or IL-1β-dependent exacerbation of excitotoxic damage.

Towards the discovery of novel genetic component involved in stress resistance in Arabidopsis thaliana.

PubMed

Juraniec, Michal; Lequeux, Hélène; Hermans, Christian; Willems, Glenda; Nordborg, Magnus; Schneeberger, Korbinian; Salis, Pietrino; Vromant, Maud; Lutts, Stanley; Verbruggen, Nathalie

2014-02-01

The exposure of plants to high concentrations of trace metallic elements such as copper involves a remodeling of the root system, characterized by a primary root growth inhibition and an increase in the lateral root density. These characteristics constitute easy and suitable markers for screening mutants altered in their response to copper excess. A forward genetic approach was undertaken in order to discover novel genetic factors involved in the response to copper excess. A Cu(2+) -sensitive mutant named copper modified resistance1 (cmr1) was isolated and a causative mutation in the CMR1 gene was identified by using positional cloning and next-generation sequencing. CMR1 encodes a plant-specific protein of unknown function. The analysis of the cmr1 mutant indicates that the CMR1 protein is required for optimal growth under normal conditions and has an essential role in the stress response. Impairment of the CMR1 activity alters root growth through aberrant activity of the root meristem, and modifies potassium concentration and hormonal balance (ethylene production and auxin accumulation). Our data support a putative role for CMR1 in cell division regulation and meristem maintenance. Research on the role of CMR1 will contribute to the understanding of the plasticity of plants in response to changing environments. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Characterization of a polyketide synthase in Aspergillus niger whose product is a precursor for both dihydroxynaphthalene (DHN) melanin and naphtho-γ-pyrone.

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

Chiang, Yi Ming; Meyer, Kristen M; Praseuth, Michael

2010-12-06

The genome sequencing of the fungus Aspergillus niger, an industrial workhorse, uncovered a large cache of genes encoding enzymes thought to be involved in the production of secondary metabolites yet to be identified. Identification and structural characterization of many of these predicted secondary metabolites are hampered by their low concentration relative to the known A. niger metabolites such as the naphtho-γ-pyrone family of polyketides. We deleted a nonreducing PKS gene in A. niger strain ATCC 11414, a daughter strain of A. niger ATCC strain 1015 whose genome was sequenced by the DOE Joint Genome Institute. This PKS encoding gene ismore » a predicted ortholog of alb1 from Aspergillus fumigatus which is responsible for production of YWA1, a precursor of fungal DHN melanin. Our results show that the A. niger alb1 PKS is responsible for the production of the polyketide precursor for DHN melanin biosynthesis. Deletion of alb1 elimnates the production of major metabolites, naphtho-γ-pyrones. The generation of an A. niger strain devoid of naphtho-γ-pyrones will greatly facilitate the elucidation of cryptic biosynthetic pathways in this organism.« less

Proteomic profile of the Bradysia odoriphaga in response to the microbial secondary metabolite benzothiazole.

PubMed

Zhao, Yunhe; Cui, Kaidi; Xu, Chunmei; Wang, Qiuhong; Wang, Yao; Zhang, Zhengqun; Liu, Feng; Mu, Wei

2016-11-24

Benzothiazole, a microbial secondary metabolite, has been demonstrated to possess fumigant activity against Sclerotinia sclerotiorum, Ditylenchus destructor and Bradysia odoriphaga. However, to facilitate the development of novel microbial pesticides, the mode of action of benzothiazole needs to be elucidated. Here, we employed iTRAQ-based quantitative proteomics analysis to investigate the effects of benzothiazole on the proteomic expression of B. odoriphaga. In response to benzothiazole, 92 of 863 identified proteins in B. odoriphaga exhibited altered levels of expression, among which 14 proteins were related to the action mechanism of benzothiazole, 11 proteins were involved in stress responses, and 67 proteins were associated with the adaptation of B. odoriphaga to benzothiazole. Further bioinformatics analysis indicated that the reduction in energy metabolism, inhibition of the detoxification process and interference with DNA and RNA synthesis were potentially associated with the mode of action of benzothiazole. The myosin heavy chain, succinyl-CoA synthetase and Ca + -transporting ATPase proteins may be related to the stress response. Increased expression of proteins involved in carbohydrate metabolism, energy production and conversion pathways was responsible for the adaptive response of B. odoriphaga. The results of this study provide novel insight into the molecular mechanisms of benzothiazole at a large-scale translation level and will facilitate the elucidation of the mechanism of action of benzothiazole.

PecS is a global regulator of the symptomatic phase in the phytopathogenic bacterium Erwinia chrysanthemi 3937.

PubMed

Hommais, Florence; Oger-Desfeux, Christine; Van Gijsegem, Frédérique; Castang, Sandra; Ligori, Sandrine; Expert, Dominique; Nasser, William; Reverchon, Sylvie

2008-11-01

Pathogenicity of the enterobacterium Erwinia chrysanthemi (Dickeya dadantii), the causative agent of soft-rot disease in many plants, is a complex process involving several factors whose production is subject to temporal regulation during infection. PecS is a transcriptional regulator that controls production of various virulence factors. Here, we used microarray analysis to define the PecS regulon and demonstrated that PecS notably regulates a wide range of genes that could be linked to pathogenicity and to a group of genes concerned with evading host defenses. Among the targets are the genes encoding plant cell wall-degrading enzymes and secretion systems and the genes involved in flagellar biosynthesis, biosurfactant production, and the oxidative stress response, as well as genes encoding toxin-like factors such as NipE and hemolysin-coregulated proteins. In vitro experiments demonstrated that PecS interacts with the regulatory regions of five new targets: an oxidative stress response gene (ahpC), a biosurfactant synthesis gene (rhlA), and genes encoding exported proteins related to other plant-associated bacterial proteins (nipE, virK, and avrL). The pecS mutant provokes symptoms more rapidly and with more efficiency than the wild-type strain, indicating that PecS plays a critical role in the switch from the asymptomatic phase to the symptomatic phase. Based on this, we propose that the temporal regulation of the different groups of genes required for the asymptomatic phase and the symptomatic phase is, in part, the result of a gradual modulation of PecS activity triggered during infection in response to changes in environmental conditions emerging from the interaction between both partners.

PecS Is a Global Regulator of the Symptomatic Phase in the Phytopathogenic Bacterium Erwinia chrysanthemi 3937▿ †

PubMed Central

Hommais, Florence; Oger-Desfeux, Christine; Van Gijsegem, Frédérique; Castang, Sandra; Ligori, Sandrine; Expert, Dominique; Nasser, William; Reverchon, Sylvie

2008-01-01

Pathogenicity of the enterobacterium Erwinia chrysanthemi (Dickeya dadantii), the causative agent of soft-rot disease in many plants, is a complex process involving several factors whose production is subject to temporal regulation during infection. PecS is a transcriptional regulator that controls production of various virulence factors. Here, we used microarray analysis to define the PecS regulon and demonstrated that PecS notably regulates a wide range of genes that could be linked to pathogenicity and to a group of genes concerned with evading host defenses. Among the targets are the genes encoding plant cell wall-degrading enzymes and secretion systems and the genes involved in flagellar biosynthesis, biosurfactant production, and the oxidative stress response, as well as genes encoding toxin-like factors such as NipE and hemolysin-coregulated proteins. In vitro experiments demonstrated that PecS interacts with the regulatory regions of five new targets: an oxidative stress response gene (ahpC), a biosurfactant synthesis gene (rhlA), and genes encoding exported proteins related to other plant-associated bacterial proteins (nipE, virK, and avrL). The pecS mutant provokes symptoms more rapidly and with more efficiency than the wild-type strain, indicating that PecS plays a critical role in the switch from the asymptomatic phase to the symptomatic phase. Based on this, we propose that the temporal regulation of the different groups of genes required for the asymptomatic phase and the symptomatic phase is, in part, the result of a gradual modulation of PecS activity triggered during infection in response to changes in environmental conditions emerging from the interaction between both partners. PMID:18790868

The segment as the minimal planning unit in speech production and reading aloud: evidence and implications.

PubMed

Kawamoto, Alan H; Liu, Qiang; Kello, Christopher T

2015-01-01

Speech production and reading aloud studies have much in common, especially the last stages involved in producing a response. We focus on the minimal planning unit (MPU) in articulation. Although most researchers now assume that the MPU is the syllable, we argue that it is at least as small as the segment based on negative response latencies (i.e., response initiation before presentation of the complete target) and longer initial segment durations in a reading aloud task where the initial segment is primed. We also discuss why such evidence was not found in earlier studies. Next, we rebut arguments that the segment cannot be the MPU by appealing to flexible planning scope whereby planning units of different sizes can be used due to individual differences, as well as stimulus and experimental design differences. We also discuss why negative response latencies do not arise in some situations and why anticipatory coarticulation does not preclude the segment MPU. Finally, we argue that the segment MPU is also important because it provides an alternative explanation of results implicated in the serial vs. parallel processing debate.

Extending the performance of single-degree-of-freedom rate integrating gyros in strapdown applications

NASA Astrophysics Data System (ADS)

Baker, G. N.

This paper examines the constraints upon a typical manufacturer of gyros and strapdown systems. It describes that while being responsive to exchange and keeping abreast of 'state of the art' technology, there are many reasons why the manufacturer must satisfy the market using existing technology and production equipment. The Single-Degree-of-Freedom Rate Integrating Gyro is a well established product, yet is capable of achieving far higher performances than originally envisaged due to modelling and characterization within digital strapdown systems. The parameters involved are discussed, and a description given of the calibration process undertaken on a strapdown system being manufactured in a production environment in batch quantities.

Growth and Development Symposium: Inflammation: Role in the etiology and pathophysiology of clinical mastitis in dairy cows.

PubMed

Ballou, M A

2012-05-01

Genetic selection for increased milk production in dairy cattle was not associated with an attenuated inflammatory response. The systemic and local inflammatory responses contribute to altered metabolism, reduced production performance, and increased cull rate of lactating dairy cows with clinical mastitis. More aggressive inflammatory responses were observed during the peripartum period when compared with cows in late lactation after an intramammary challenge with purified lipopolysaccharide. The epidemiology of clinical mastitis indicates that the greatest incidence is observed during the peripartum period; therefore, an enhanced inflammatory response with concomitant suppression in other immune responses may be involved in the etiology and severity of the clinical mastitis observed in peripartum cows. Milk production losses and compositional changes are observed among all mammary quarters from a cow with clinical mastitis, but the responses are more severe and sustained among infected quarters. The infected mammary quarters reflect both the systemic and local reactions, whereas uninfected quarters represent only the systemic response. The systemic effects of the inflammatory response include reduced DMI, hyperthermia, and changes in whole-body nutrient partitioning affecting mammary epithelial substrate availability, whereas local inflammatory effects include energetic requirements of the increased inflammatory leukocyte pool, decreased synthetic capacity of mammary epithelium independent of substrate availability, and paracellular leakage of milk components from the alveolar lumen into the extracellular fluid. Research has focused on improving host immunological defenses, attenuating the inflammatory response, or improving the resolution of the disease state to limit the deleterious effects during clinical mastitis. This paper highlights the role inflammation plays in the etiology and pathophysiology of clinical mastitis as well as potential management strategies to reduce or prevent those losses.

Membrane-derived second messenger regulates x-ray-mediated tumor necrosis factor alpha gene induction.

PubMed Central

Hallahan, D E; Virudachalam, S; Kuchibhotla, J; Kufe, D W; Weichselbaum, R R

1994-01-01

Cells adapt to adverse environmental conditions through a wide range of responses that are conserved throughout evolution. Physical agents such as ionizing radiation are known to initiate a stress response that is triggered by the recognition of DNA damage. We have identified a signaling pathway involving the activation of phospholipase A2 and protein kinase C in human cells that confers x-ray induction of the tumor necrosis factor alpha gene. Treatment of human cells with ionizing radiation or H2O2 was associated with the production of arachidonic acid. Inhibition of phospholipase A2 abolished radiation-mediated arachidonate production as well as the subsequent activation of protein kinase C and tumor necrosis factor alpha gene expression. These findings demonstrate that ionizing radiation-mediated gene expression in human cells is regulated in part by extranuclear signal transduction. One practical application of phospholipase A2 inhibitors is to ameliorate the adverse effects of radiotherapy associated with tumor necrosis factor alpha production. Images PMID:8197153

Expression and purification of functional JNK2beta2: perspectives on high-level production of recombinant MAP kinases.

PubMed

Savopoulos, John W; Dowd, Stephen; Armour, Carolyn; Carter, Paul S; Greenwood, Catherine J; Mills, David; Powell, David; Pettman, Gary R; Jenkins, Owen; Walsh, Frank S; Philpott, Karen L

2002-02-01

The mitogen-activated protein (MAP) kinases are a group of serine/threonine kinases that mediate intracellular signal transduction in response to environmental stimuli including stress, growth factors, and various cytokines. Of this family, the c-Jun N-terminal kinases (JNKs) are members which, depending on cell type, have been shown to activate the transcription of genes involved in the inflammatory response, apoptosis, and hypertrophy. Here we report the use Baculovirus/Sf9 cells to produce milligram quantities of recombinant JNK2beta2 substrate which could be purified to >90% as judged by SDS-PAGE. In addition, we report a novel method for the site-specific biotinylation for this enzyme and demonstrate that the biotinylated product is an authentic substrate of the upstream kinases MKK4 and 7 and can phosphorylate a downstream target, ATF-2. We also show that the phosphorylated product can be captured efficiently on streptavidin-coated beads for use in scintillation proximity assays. Copyright 2002 Elsevier Science (USA).

Overexpression of MicA induces production of OmpC-enriched outer membrane vesicles that protect against Salmonella challenge.

PubMed

Choi, Hyun-Il; Kim, Moonjeong; Jeon, Jinseong; Han, Jin Kwan; Kim, Kwang-Sun

2017-08-26

Outer membrane vesicles (OMVs) derived from bacteria are promising candidates for subunit vaccines. Stresses that modulate the composition of outer membrane proteins (OMPs) are important for OMV synthesis. Small RNAs (sRNAs) expressed in response to stress regulate OMPs, although the mechanism underlying sRNA-mediated OMV biogenesis and its utility for developing vaccine platforms remains to be elucidated. Here, we characterized the role of a sRNA, MicA, which regulates OmpA, a major OMP involved in both production of OMVs and reactive immunity against Salmonella challenge. A Salmonella strain overexpressing MicA generated more OMVs than a control strain. In addition, OmpC was the major component of MicA-derived OMV proteins. MicA-derived OMVs induced Th1- and Th17-type immune responses in vitro and reduced Salmonella-mediated lethality in a mouse model. Thus, OmpA-regulatory sRNA-derived OMVs may facilitate production of Salmonella-protective vaccines. Copyright © 2017 Elsevier Inc. All rights reserved.

Volatile fatty acids productions by mesophilic and thermophilic sludge fermentation: Biological responses to fermentation temperature.

PubMed

Hao, Jiuxiao; Wang, Hui

2015-01-01

The volatile fatty acids (VFAs) productions, as well as hydrolases activities, microbial communities, and homoacetogens, of mesophilic and thermophilic sludge anaerobic fermentation were investigated to reveal the microbial responses to different fermentation temperatures. Thermophilic fermentation led to 10-fold more accumulation of VFAs compared to mesophilic fermentation. α-glucosidase and protease had much higher activities in thermophilic reactor, especially protease. Illumina sequencing manifested that raising fermentation temperature increased the abundances of Clostridiaceae, Microthrixaceae and Thermotogaceae, which could facilitate either hydrolysis or acidification. Real-time PCR analysis demonstrated that under thermophilic condition the relative abundance of homoacetogens increased in batch tests and reached higher level at stable fermentation, whereas under mesophilic condition it only increased slightly in batch tests. Therefore, higher fermentation temperature increased the activities of key hydrolases, raised the proportions of bacteria involved in hydrolysis and acidification, and promoted the relative abundance of homoacetogens, which all resulted in higher VFAs production. Copyright © 2014 Elsevier Ltd. All rights reserved.

Optimization of Manganese Reduction in Biotreated POME onto 3A Molecular Sieve and Clinoptilolite Zeolites.

PubMed

Jami, Mohammed S; Rosli, Nurul-Shafiqah; Amosa, Mutiu K

2016-06-01

Availability of quality-certified water is pertinent to the production of food and pharmaceutical products. Adverse effects of manganese content of water on the corrosion of vessels and reactors necessitate that process water is scrutinized for allowable concentration levels before being applied in the production processes. In this research, optimization of the adsorption process conditions germane to the removal of manganese from biotreated palm oil mill effluent (BPOME) using zeolite 3A subsequent to a comparative adsorption with clinoptilolite was studied. A face-centered central composite design (FCCCD) of the response surface methodology (RSM) was adopted for the study. Analysis of variance (ANOVA) for response surface quadratic model revealed that the model was significant with dosage and agitation speed connoting the main significant process factors for the optimization. R(2) of 0.9478 yielded by the model was in agreement with predicted R(2). Langmuir and pseudo-second-order suggest the adsorption mechanism involved monolayer adsorption and cation exchanging.

Exploring the host transcriptome for mechanisms underlying protective immunity and resistance to nematode infections in ruminants.

PubMed

Li, Robert W; Choudhary, Ratan K; Capuco, Anthony V; Urban, Joseph F

2012-11-23

Nematode infections in ruminants are a major impediment to the profitable production of meat and dairy products, especially for small farms. Gastrointestinal parasitism not only negatively impacts weight gain and milk yield, but is also a major cause of mortality in small ruminants. The current parasite control strategy involves heavy use of anthelmintics that has resulted in the emergence of drug-resistant parasite strains. This, in addition to increasing consumer demand for animal products that are free of drug residues has stimulated development of alternative strategies, including selective breeding of parasite resistant ruminants. The development of protective immunity and manifestations of resistance to nematode infections relies upon the precise expression of the host genome that is often confounded by mechanisms simultaneously required to control multiple nematode species as well as ecto- and protozoan parasites, and microbial and viral pathogens. Understanding the molecular mechanisms underlying these processes represents a key step toward development of effective new parasite control strategies. Recent progress in characterizing the transcriptome of both hosts and parasites, utilizing high-throughput microarrays and RNA-seq technology, has led to the recognition of unique interactions and the identification of genes and biological pathways involved in the response to parasitism. Innovative use of the knowledge gained by these technologies should provide a basis for enhancing innate immunity while limiting the polarization of acquired immunity can negatively affect optimal responses to co-infection. Strategies for parasite control that use diet and vaccine/adjuvant combination could be evaluated by monitoring the host transcriptome for induction of appropriate mechanisms for imparting parasite resistance. Knowledge of different mechanisms of host immunity and the critical regulation of parasite development, physiology, and virulence can also selectively identify targets for parasite control. Comparative transcriptome analysis, in concert with genome-wide association (GWS) studies to identify quantitative trait loci (QTLs) affecting host resistance, represents a promising molecular technology to evaluate integrated control strategies that involve breed and environmental factors that contribute to parasite resistance and improved performance. Tailoring these factors to control parasitism without severely affecting production qualities, management efficiencies, and responses to pathogenic co-infection will remain a challenge. This review summarizes recent progress and limitations of understanding regulatory genetic networks and biological pathways that affect host resistance and susceptibility to nematode infection in ruminants. Published by Elsevier B.V.

Biological Networks Underlying Abiotic Stress Tolerance in Temperate Crops—A Proteomic Perspective

PubMed Central

Kosová, Klára; Vítámvás, Pavel; Urban, Milan Oldřich; Klíma, Miroslav; Roy, Amitava; Prášil, Ilja Tom

2015-01-01

Abiotic stress factors, especially low temperatures, drought, and salinity, represent the major constraints limiting agricultural production in temperate climate. Under the conditions of global climate change, the risk of damaging effects of abiotic stresses on crop production increases. Plant stress response represents an active process aimed at an establishment of novel homeostasis under altered environmental conditions. Proteins play a crucial role in plant stress response since they are directly involved in shaping the final phenotype. In the review, results of proteomic studies focused on stress response of major crops grown in temperate climate including cereals: common wheat (Triticum aestivum), durum wheat (Triticum durum), barley (Hordeum vulgare), maize (Zea mays); leguminous plants: alfalfa (Medicago sativa), soybean (Glycine max), common bean (Phaseolus vulgaris), pea (Pisum sativum); oilseed rape (Brassica napus); potato (Solanum tuberosum); tobacco (Nicotiana tabaccum); tomato (Lycopersicon esculentum); and others, to a wide range of abiotic stresses (cold, drought, salinity, heat, imbalances in mineral nutrition and heavy metals) are summarized. The dynamics of changes in various protein functional groups including signaling and regulatory proteins, transcription factors, proteins involved in protein metabolism, amino acid metabolism, metabolism of several stress-related compounds, proteins with chaperone and protective functions as well as structural proteins (cell wall components, cytoskeleton) are briefly overviewed. Attention is paid to the differences found between differentially tolerant genotypes. In addition, proteomic studies aimed at proteomic investigation of multiple stress factors are discussed. In conclusion, contribution of proteomic studies to understanding the complexity of crop response to abiotic stresses as well as possibilities to identify and utilize protein markers in crop breeding processes are discussed. PMID:26340626

Injury and immune response: applying the danger theory to mosquitoes

PubMed Central

Moreno-García, Miguel; Recio-Tótoro, Benito; Claudio-Piedras, Fabiola; Lanz-Mendoza, Humberto

2014-01-01

The insect immune response can be activated by the recognition of both non-self and molecular by-products of tissue damage. Since pathogens and tissue damage usually arise at the same time during infection, the specific mechanisms of the immune response to microorganisms, and to tissue damage have not been unraveled. Consequently, some aspects of damage caused by microorganisms in vector-borne arthropods have been neglected. We herein reassess the Anopheles–Plasmodium interaction, incorporating Matzinger’s danger/damage hypothesis and George Salt’s injury assumptions. The invasive forms of the parasite cross the peritrophic matrix and midgut epithelia to reach the basal lamina and differentiate into an oocyst. The sporozoites produced in the oocyst are released into the hemolymph, and from there enter the salivary gland. During parasite development, wounds to midgut tissue and the basement membrane are produced. We describe the response of the different compartments where the parasite interacts with the mosquito. In the midgut, the response includes the expression of antimicrobial peptides, production of reactive oxygen species, and possible activation of midgut regenerative cells. In the basal membrane, wound repair mainly involves the production of molecules and the recruitment of hemocytes. We discuss the susceptibility to damage in tissues, and how the place and degree of damage may influence the differential response and the expression of damage associated molecular patterns (DAMPs). Knowledge about damage caused by parasites may lead to a deeper understanding of the relevance of tissue damage and the immune response it generates, as well as the origins and progression of infection in this insect–parasite interaction. PMID:25250040

A pivotal role of vacuolar H(+)-ATPase in regulation of lipid production in Phaeodactylum tricornutum.

PubMed

Zhang, Huiying; Zeng, Rensen; Chen, Daoyi; Liu, Jian

2016-08-08

Microalgal lipids have been considered as a promising source for biodiesel production. Alkaline pH can induce neutral lipid accumulation in microalgae cells. However, whether and how proton pumps, especially vacuolar H(+)-ATPase (V-ATPase), function in these processes is not well known. In this study, we treated Phaeodactylum tricornutum with V-ATPase specific inhibitor bafilomycin A1 (BFA1) to determine its role in lipid production. Firstly, V-ATPase activity was increased in the latter phase of microalgae growth. BFA1 treatment decreased the cell density and lipid contents. Further analysis showed that BFA1 treatment reduced the number and size of oil bodies. GC-MS analysis showed that lipid components were not affected by BFA1 treatment. Intracellular pH was decreased and nitrogen depletion was delayed after BFA1 treatment. RNA-Seq analysis showed that expression of genes involved in calcium signaling, sulfur metabolism, cell cycle, glycolysis, pentose phosphate pathway, porphyrin, chlorophyll metabolism and lipid catabolic metabolism were upregulated, while expression of genes involved in ion transmembrane transport, ubiquitin mediated proteolysis, SNARE interactions in vesicular transport, fatty acid biosynthesis were downregulated under BFA1 treatment. Our findings provided insights into the molecular mechanisms underlying lipid accumulation and the key genes involved in lipid metabolism in Phaeodactylum tricornutum in response to BFA1.

Hyperprolactinemia following chronic alcohol administration.

PubMed

Sarkar, Dipak K

2010-01-01

There are several reports showing evidence for the existence of high levels of prolactin (PRL) in alcoholic men and women. Alcohol-induced hyperprolactinemia has also been demonstrated in nonhuman primates and laboratory animals. Therefore, the clinical data as well as animal data suggest that ethanol consumption is a positive risk factor for hyperprolactinemia. In animal studies, it was found that chronic ethanol administration not only elevates plasma levels of PRL but also increases proliferation of pituitary lactotropes. Ethanol action on lactotropes involves crosstalk with estradiol-responsive signaling cascade or estradiol-regulated cell-cell communication. Additionally, it involves suppression of dopamine D2 receptors inhibition of G proteins and intracellular cyclic adenosine monophosphate (cAMP), modulation of transforming growth factor-beta (TGF-beta) isoforms and their receptors (TbetaRII), as well as factors secondary to TGF-beta actions, including production of beta-fibroblast growth factor (bFGF) from follicular-stellate cells. The downstream signaling that governs b-FGF production and secretion involves activation of the MAP kinase p44/42-dependent pathway. A coordinated suppression of D2 receptor- and TbetaRII receptor-mediated signaling as well as enhancement of bFGF activity might be critical for ethanol action on PRL production and cell proliferation in lactotropes. Copyright (c) 2010 S. Karger AG, Basel.

Oxidative Stress and Phthalate-Induced Down-Regulation of Steroidogenesis in MA-10 Leydig Cells*

PubMed Central

Zhou, Liang; Beattie, Matthew C.; Lin, Chieh-Yin; Liu, June; Traore, Kassim; Papadopoulos, Vassilios; Zirkin, Barry R.; Chen, Haolin

2013-01-01

Previous studies have shown that phthalate exposure can suppress steroidogenesis. However, the affected components of the steroidogenic pathway, and the mechanisms involved, remain uncertain. We show that incubating MA-10 Leydig cells with mono-(2-ethylhexyl) phthalate (MEHP) resulted in reductions in luteinizing hormone (LH)-stimulated cAMP and progesterone productions. cAMP did not decrease in response to MEHP when the cells were incubated with cholera toxin or forskolin. Incubation of MEHP-treated cells with dibutyryl-cAMP, 22-hydroxycholesterol or pregnenolone inhibited the reductions in progesterone. Increased levels of reactive oxygen species (ROS) occurred in response to MEHP. In cells in which intracellular glutathione was depleted by buthionine sulfoximine pretreatment, the increases in ROS and decreases in progesterone in response to MEHP treatment were exacerbated. These results indicate that MEHP inhibits MA-10 Leydig cell steroidogenesis by targeting LH-stimulated cAMP production and cholesterol transport, and that a likely mechanism by which MEHP acts is through increased oxidative stress. PMID:23969005

Osmotic stress response in the wine yeast Dekkera bruxellensis.

PubMed

Galafassi, Silvia; Toscano, Marco; Vigentini, Ileana; Piškur, Jure; Compagno, Concetta

2013-12-01

Dekkera bruxellensis is mainly associated with lambic beer fermentation and wine production and may contribute in a positive or negative manner to the flavor development. This yeast is able to produce phenolic compounds, such as 4-ethylguaiacol and 4-ethylphenol which could spoil the wine, depending on their concentration. In this work we have investigated how this yeast responds when exposed to conditions causing osmotic stress, as high sorbitol or salt concentrations. We observed that osmotic stress determined the production and accumulation of intracellular glycerol, and the expression of NADH-dependent glycerol-3-phosphate dehydrogenase (GPD) activity was elevated. The involvement of the HOG MAPK pathway in response to this stress condition was also investigated. We show that in D. bruxellensis Hog1 protein is activated by phosphorylation under hyperosmotic conditions, highlighting the conserved role of HOG MAP kinase signaling pathway in the osmotic stress response. Gene Accession numbers in GenBank: DbHOG1: JX65361, DbSTL1: JX965362. Copyright © 2013 Elsevier Ltd. All rights reserved.

Allergic responses and aryl hydrocarbon receptor novel pathway of mast cell activation.

PubMed

Sibilano, Riccardo; Pucillo, Carlo E; Gri, Giorgia

2015-01-01

The activation of the transcription factor aryl hydrocarbon receptor (AhR) is modulated by a wide variety of xenobiotics and ligands deriving from products of metabolism. The study of the contribution of AhR to allergic diseases has gained much interest in recent years. Here we discuss the role that environmental factors and metabolic products, particularly acting on AhR-expressing mast cells (MCs), could have in the development of local allergic/atopic response. Thus, this review will cover: a brief overview of the AhR mechanism of action in the immune system; a description of different AhR ligands and their effects to IgE-mediated MC activation in the allergic response, with particular attention to the role of IL-17; a discussion about the potential involvement of AhR in immune tolerance; and a conclusion on human diseases in which direct AhR activation of MC might have a major impact. Copyright © 2014 Elsevier Ltd. All rights reserved.

Non-Specific Microbicide Product Development: Then and Now

PubMed Central

Romano, Joseph W.; Robbiani, Melissa; Doncel, Gustavo F.; Moench, Thomas

2015-01-01

Despite the identification of HIV-1 as the etiological agent responsible for AIDS nearly 30 years ago, a sterilizing vaccine capable of preventing transmission of the virus remains elusive. In response to struggles on the vaccine development front, significant effort has been devoted to preventing the transmission of HIV with alternative products, technologies, and strategies. One of the early alternative HIV prevention strategies was microbicides, which are topical products that can be used to prevent sexual transmission of HIV either vaginally or rectally. First generation microbicide products were designed to be simple gel formulations comprised of readily available active agents that were inexpensive and broadly active (i.e., non-specific). Unfortunately, despite the clinical investigation of multiple product concepts satisfying these requirements, none were shown to be efficacious in pivotal trials. More recently, microbicide and oral prevention strategies involving highly specific and potent anti-retroviral (ARV) drugs have shown to be efficacious in trials. Although building on these successes continues, these products have a number of issues including potential toxicity with long term use, selection of HIV resistance, and cost. Further, all of the original justifications for non-specific microbicide products remain valid. This review provides a brief history of non-specific microbicide development, outlines the evolution to, and limitations of, ARV based microbicides, and summarizes the current activity on non-specific microbicide product development. PMID:22264041

Blockchain Based Decentralized Management of Demand Response Programs in Smart Energy Grids.

PubMed

Pop, Claudia; Cioara, Tudor; Antal, Marcel; Anghel, Ionut; Salomie, Ioan; Bertoncini, Massimo

2018-01-09

In this paper, we investigate the use of decentralized blockchain mechanisms for delivering transparent, secure, reliable, and timely energy flexibility, under the form of adaptation of energy demand profiles of Distributed Energy Prosumers, to all the stakeholders involved in the flexibility markets (Distribution System Operators primarily, retailers, aggregators, etc.). In our approach, a blockchain based distributed ledger stores in a tamper proof manner the energy prosumption information collected from Internet of Things smart metering devices, while self-enforcing smart contracts programmatically define the expected energy flexibility at the level of each prosumer, the associated rewards or penalties, and the rules for balancing the energy demand with the energy production at grid level. Consensus based validation will be used for demand response programs validation and to activate the appropriate financial settlement for the flexibility providers. The approach was validated using a prototype implemented in an Ethereum platform using energy consumption and production traces of several buildings from literature data sets. The results show that our blockchain based distributed demand side management can be used for matching energy demand and production at smart grid level, the demand response signal being followed with high accuracy, while the amount of energy flexibility needed for convergence is reduced.

Genome scale transcriptomics of baculovirus-insect interactions.

PubMed

Nguyen, Quan; Nielsen, Lars K; Reid, Steven

2013-11-12

Baculovirus-insect cell technologies are applied in the production of complex proteins, veterinary and human vaccines, gene delivery vectors' and biopesticides. Better understanding of how baculoviruses and insect cells interact would facilitate baculovirus-based production. While complete genomic sequences are available for over 58 baculovirus species, little insect genomic information is known. The release of the Bombyx mori and Plutella xylostella genomes, the accumulation of EST sequences for several Lepidopteran species, and especially the availability of two genome-scale analysis tools, namely oligonucleotide microarrays and next generation sequencing (NGS), have facilitated expression studies to generate a rich picture of insect gene responses to baculovirus infections. This review presents current knowledge on the interaction dynamics of the baculovirus-insect system' which is relatively well studied in relation to nucleocapsid transportation, apoptosis, and heat shock responses, but is still poorly understood regarding responses involved in pro-survival pathways, DNA damage pathways, protein degradation, translation, signaling pathways, RNAi pathways, and importantly metabolic pathways for energy, nucleotide and amino acid production. We discuss how the two genome-scale transcriptomic tools can be applied for studying such pathways and suggest that proteomics and metabolomics can produce complementary findings to transcriptomic studies.

Microparticle formation by platelets exposed to high gas pressures - An oxidative stress response.

PubMed

Bhullar, Jasjeet; Bhopale, Veena M; Yang, Ming; Sethuraman, Kinjal; Thom, Stephen R

2016-12-01

This investigation explored the mechanism for microparticles (MPs) production by human and murine platelets exposed to high pressures of inert gases. Results demonstrate that MPs production occurs via an oxidative stress response in a dose-dependent manner and follows the potency series N 2 >Ar>He. Gases with higher van der Waals volumes or polarizability such as SF 6 and N 2 O, or hydrostatic pressure, do not cause MPs production. Singlet O 2 is generated by N 2 , Ar and He, which is linked to NADPH oxidase (NOX) activity. Progression of oxidative stress involves activation of nitric oxide synthase (NOS) leading to S-nitrosylation of cytosolic actin. Exposure to gases enhances actin filament turnover and associations between short actin filaments, NOS, vasodilator-stimulated phosphoprotein (VASP), focal adhesion kinase (FAK) and Rac1. Inhibition of NOS or NOX by chemical inhibitors or using platelets from mice lacking NOS2 or the gp91phox component of NOX diminish generation of reactive species, enhanced actin polymerization and MP generation by high pressure gases. We conclude that by initiating a sequence of progressive oxidative stress responses high pressure gases cause platelets to generate MPs. Copyright © 2016 Elsevier Inc. All rights reserved.

Modelling and Optimization of Polycaprolactone Ultrafine-Fibres Electrospinning Process Using Response Surface Methodology

PubMed Central

Ruys, Andrew J.

2018-01-01

Electrospun fibres have gained broad interest in biomedical applications, including tissue engineering scaffolds, due to their potential in mimicking extracellular matrix and producing structures favourable for cell and tissue growth. The development of scaffolds often involves multivariate production parameters and multiple output characteristics to define product quality. In this study on electrospinning of polycaprolactone (PCL), response surface methodology (RSM) was applied to investigate the determining parameters and find optimal settings to achieve the desired properties of fibrous scaffold for acetabular labrum implant. The results showed that solution concentration influenced fibre diameter, while elastic modulus was determined by solution concentration, flow rate, temperature, collector rotation speed, and interaction between concentration and temperature. Relationships between these variables and outputs were modelled, followed by an optimization procedure. Using the optimized setting (solution concentration of 10% w/v, flow rate of 4.5 mL/h, temperature of 45 °C, and collector rotation speed of 1500 RPM), a target elastic modulus of 25 MPa could be achieved at a minimum possible fibre diameter (1.39 ± 0.20 µm). This work demonstrated that multivariate factors of production parameters and multiple responses can be investigated, modelled, and optimized using RSM. PMID:29562614

NK Cells and Their Ability to Modulate T Cells during Virus Infections

PubMed Central

Cook, Kevin D.; Waggoner, Stephen N.; Whitmire, Jason K.

2014-01-01

Natural killer (NK) cells are important in protection against virus infections, and many viruses have evolved mechanisms to thwart NK cell activity. NK cells respond to inflammatory signals at an early stage of virus infection, resulting in proliferation, cytokine production, and cytolytic activity that can reduce virus loads. Moreover, the rapid kinetics of the NK cell response enables NK cells to influence other populations of innate immune cells, affect the inflammatory milieu, and guide adaptive immune responses to infection. Early NK cell interactions with other leukocytes can have long-lasting effects on the number and quality of memory T cells, as well as impact the exhaustion of T cells during chronic infections. The ability of NK cells to modulate T cell responses can be mediated through direct T-NK interactions, cytokine production, or indirectly through dendritic cells and other cell types. Herein, we summarize our current understanding of how NK cells interact with T cells, dendritic cells, B cells, and other cell types involved in adaptive immune responses to virus infection. We outline several mechanisms by which NK cells enhance or suppress adaptive immune response and long-lived immunological memory. PMID:25404045

Atrazine and increased male production by Daphnia: the importance of combining field and laboratory approaches.

PubMed

Stoeckel, James A; González, María J; Oris, James T; Kovach, Mathew J; Mace, Kimberly M

2008-11-01

Atrazine is one of the most commonly applied herbicides in North America and annually pulses through many midwestern stream and reservoir systems. Previous studies have yielded conflicting results regarding the ability of atrazine to stimulate male production by Daphnia, an effect hypothesized to lower population growth rates during a period of intense larval fish predation. In the present study, populations of Daphnia parvula and Daphnia ambigua exhibited high proportions of males but no ephippial females when atrazine pulsed into Acton Lake, a small midwestern reservoir. Field results thus supported the hypothesis of excess male production by Daphnia during the spring herbicide pulse. In laboratory studies, dose-response studies, and population-level assays revealed no effect of atrazine on male production or population growth rate of multiple clones differing in reproductive strategy and exposure history. However, D. parvula increased male production in response to an endogenous crustacean hormone (methyl farnesoate). Excess male production observed in the field population was therefore not likely caused by atrazine, although we cannot rule out the possibility of interactive effects of atrazine and some other stressor. Apparent signs of endocrine disruption in the presence of high concentrations of a suspected agent should be viewed with caution in the absence of parallel laboratory studies involving individuals from the populations of interest.

The role of veterinary services in animal health and food safety surveillance, and coordination with other services.

PubMed

Bellemain, V

2013-08-01

The control of animal health and food safety has undergone profound changes and is now seen in terms of a global approach, 'from the stable to the table'. The risks themselves have also evolved, principally due to changing practices, and this, coupled with increased knowledge and changes in consumer demands, has led to a more global conception of production chains. In terms of official controls, targeted control of the final food product has gradually been replaced by control of the production processes and an integrated approach to hazards throughout the production chain. This, in turn, has resulted in a new division of responsibilities among the producers (farmers), the manufacturers and the administration; namely, Veterinary Services. The areas in which veterinarians are involved have gradually been extended from animal production to all levels of the food production chain. Animal health interventions on farms are comparable to interventions in agri-food companies. Both are, or should be, included in veterinary training and education. To meet new challenges, the current trend is for Veterinary Services to be responsible for, or coordinate, sanitary interventions from the stable to the table. Coordination between Veterinary Services and other relevant authorities is a key component of good public governance, especially for effective action and optimal management of the resources available.

How placebos change the patient's brain.

PubMed

Benedetti, Fabrizio; Carlino, Elisa; Pollo, Antonella

2011-01-01

Although placebos have long been considered a nuisance in clinical research, today they represent an active and productive field of research and, because of the involvement of many mechanisms, the study of the placebo effect can actually be viewed as a melting pot of concepts and ideas for neuroscience. Indeed, there exists not a single but many placebo effects, with different mechanisms and in different systems, medical conditions, and therapeutic interventions. For example, brain mechanisms of expectation, anxiety, and reward are all involved, as well as a variety of learning phenomena, such as Pavlovian conditioning, cognitive, and social learning. There is also some experimental evidence of different genetic variants in placebo responsiveness. The most productive models to better understand the neurobiology of the placebo effect are pain and Parkinson's disease. In these medical conditions, the neural networks that are involved have been identified: that is, the opioidergic-cholecystokinergic-dopaminergic modulatory network in pain and part of the basal ganglia circuitry in Parkinson's disease. Important clinical implications emerge from these recent advances in placebo research. First, as the placebo effect is basically a psychosocial context effect, these data indicate that different social stimuli, such as words and rituals of the therapeutic act, may change the chemistry and circuitry of the patient's brain. Second, the mechanisms that are activated by placebos are the same as those activated by drugs, which suggests a cognitive/affective interference with drug action. Third, if prefrontal functioning is impaired, placebo responses are reduced or totally lacking, as occurs in dementia of the Alzheimer's type.

Marketing strategies nurses can employ to promote health.

PubMed

McCormack, D

1994-01-01

Marketing strategies are employed to ensure the success of new products, services or programs. Both profit and non-profit organizations have used social marketing strategies to inform, to motivate interest, and to engage the involvement of the consumer. A client-dependent health care system did not find it necessary to market services, but a health care system that encourages clients to choose the most appropriate health promotion service available must market services. Nurses are in the business of promoting the health of clients. Therefore, it is essential that nurses become familiar with, and involved in, the development of marketing plans and strategies. The connection between the four variables of the marketing mix (product, promotion, place, and price) and promoting the health of clients is described. A case example recapitulating the marketing strategies employed to raise public awareness of a self-help group for family caregivers is related, the marketing response is evaluated, and future recommendations are proposed.

Atomistic material behavior at extreme pressures

DOE PAGES

Beland, Laurent K.; Osetskiy, Yury N.; Stoller, Roger E.

2016-08-05

Computer simulations are routinely performed to model the response of materials to extreme environments, such as neutron (or ion) irradiation. The latter involves high-energy collisions from which a recoiling atom creates a so-called atomic displacement cascade. These cascades involve coordinated motion of atoms in the form of supersonic shockwaves. These shockwaves are characterized by local atomic pressures >15 GPa and interatomic distances <2 Å. Similar pressures and interatomic distances are observed in other extreme environment, including short-pulse laser ablation, high-impact ballistic collisions and diamond anvil cells. Displacement cascade simulations using four different force fields, with initial kinetic energies ranging frommore » 1 to 40 keV, show that there is a direct relationship between these high-pressure states and stable defect production. An important shortcoming in the modeling of interatomic interactions at these short distances, which in turn determines final defect production, is brought to light.« less

Spatial Organization Plasticity as an Adaptive Driver of Surface Microbial Communities

PubMed Central

Bridier, Arnaud; Piard, Jean-Christophe; Pandin, Caroline; Labarthe, Simon; Dubois-Brissonnet, Florence; Briandet, Romain

2017-01-01

Biofilms are dynamic habitats which constantly evolve in response to environmental fluctuations and thereby constitute remarkable survival strategies for microorganisms. The modulation of biofilm functional properties is largely governed by the active remodeling of their three-dimensional structure and involves an arsenal of microbial self-produced components and interconnected mechanisms. The production of matrix components, the spatial reorganization of ecological interactions, the generation of physiological heterogeneity, the regulation of motility, the production of actives enzymes are for instance some of the processes enabling such spatial organization plasticity. In this contribution, we discussed the foundations of architectural plasticity as an adaptive driver of biofilms through the review of the different microbial strategies involved. Moreover, the possibility to harness such characteristics to sculpt biofilm structure as an attractive approach to control their functional properties, whether beneficial or deleterious, is also discussed. PMID:28775718

C-glycosylation reactions of sulfur-substituted glycosyl donors: evidence against the role of neighboring-group participation.

PubMed

Beaver, Matthew G; Billings, Susan B; Woerpel, K A

2008-02-13

Nucleophilic substitution reactions of C-4 sulfur-substituted tetrahydropyran acetals revealed that neighboring-group participation does not control product formation. Spectroscopic evidence for the formation of an intermediate sulfonium ion is provided, as are data from nucleophilic substitution reactions demonstrating that products are formed from oxocarbenium ion intermediates. The selectivity was not sensitive to solvent or to which Lewis acid was employed. The identity of the heteroatom at the C-4 position also did not significantly impact diastereoselectivity. Consequently, neighboring-group participation was not responsible for the formation of either the major or the minor products. These studies implicate a Curtin-Hammett kinetic scenario in which the formation of a low-energy intermediate does not necessitate its involvement in the product-forming pathway.

Induction of Sirt1 by Mechanical Stretch of Skeletal Muscle through the Early Response Factor EGR1 Triggers an Antioxidative Response*

PubMed Central

Pardo, Patricia S.; Mohamed, Junaith S.; Lopez, Michael A.; Boriek, Aladin M.

2011-01-01

Mechanical loading of muscles by intrinsic muscle activity or passive stretch leads to an increase in the production of reactive oxygen species (1, 2). The NAD-dependent protein deacetylase SIRT1 is involved in the protection against oxidative stress by enhancing FOXO-driven Sod2 transcription (3–5). In this report, we unravel a mechanism triggered by mechanical stretch of skeletal muscle cells that leads to an EGR1-dependent transcriptional activation of the Sirt1 gene. The resulting transient increase in SIRT1 expression generates an antioxidative response that contributes to reactive oxygen species scavenging. PMID:20971845

Towards the production of salt-tolerant crops.

PubMed

Barkla, B J; Vera-Estrella, R; Pantoja, O

1999-01-01

Crop production is affected by numerous environmental factors, with soil salinity and drought having the most detrimental effects. Attempts to improve yield under stress conditions by plant breeding have been unsuccessful, primarily due to the multigenic origin of the adaptive responses. The transfer of genes through genetic engineering of crop plants appears more feasible. Important adaptive mechanisms targeted for potential gene transfer would be the tonoplast Na+/H+ antiport, compatible solute synthesis and, regulation of water channel activity and expression, mechanisms involved in cellular osmoregulation. In this review we discuss recent advances in our understanding of these adaptive mechanisms.

Immune thrombocytopenia: No longer ‘idiopathic’

PubMed Central

McCRAE, KEITH

2012-01-01

Immune thrombocytopenia (ITP) is a common hematologic disorder. Its pathogenesis involves both accelerated platelet destruction and impaired platelet production. First-line agents are usually effective initially but do not provide long-term responses. Splenectomy remains an effective long-term therapy, as does rituximab (Rituxan) in a subset of patients. Thrombopoietic agents offer a new alternative, although their place in the overall management of ITP remains uncertain. PMID:21632906

Photocatalytic oxidation of organic compounds on Mars

NASA Technical Reports Server (NTRS)

Chun, S. F. S.; Pang, K. D.; Cutts, J. A.; Ajello, J. M.

1978-01-01

Ultraviolet-stimulated catalytic oxidation is proposed as a mechanism for the destruction of organic compounds on Mars. The process involves the presence of gaseous oxygen, UV radiation, and a catalyst (titanium dioxide), and all three of these have been found to be present in the Martian environment. Therefore it seems plausible that UV-stimulated oxidation of organics is responsible for degrading organic molecules into inorganic end products.

Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response.

PubMed

Rodríguez Pulido, Miguel; Sáiz, Margarita

2017-01-01

Foot-and-mouth disease virus (FMDV) is the causative agent of an acute vesicular disease affecting pigs, cattle and other domestic, and wild animals worldwide. The aim of the host interferon (IFN) response is to limit viral replication and spread. Detection of the viral genome and products by specialized cellular sensors initiates a signaling cascade that leads to a rapid antiviral response involving the secretion of type I- and type III-IFNs and other antiviral cytokines with antiproliferative and immunomodulatory functions. During co-evolution with their hosts, viruses have acquired strategies to actively counteract host antiviral responses and the balance between innate response and viral antagonism may determine the outcome of disease and pathogenesis. FMDV proteases Lpro and 3C have been found to antagonize the host IFN response by a repertoire of mechanisms. Moreover, the putative role of other viral proteins in IFN antagonism is being recently unveiled, uncovering sophisticated immune evasion strategies different to those reported to date for other members of the Picornaviridae family. Here, we review the interplay between antiviral responses induced by FMDV infection and viral countermeasures to block them. Research on strategies used by viruses to modulate immunity will provide insights into the function of host pathways involved in defense against pathogens and will also lead to development of new therapeutic strategies to fight virus infections.

Cold-Induced Changes in Gene Expression in Brown Adipose Tissue, White Adipose Tissue and Liver

PubMed Central

Shore, Andrew M.; Karamitri, Angeliki; Kemp, Paul; Speakman, John R.; Graham, Neil S.; Lomax, Michael A.

2013-01-01

Cold exposure imposes a metabolic challenge to mammals that is met by a coordinated response in different tissues to prevent hypothermia. This study reports a transcriptomic analysis in brown adipose tissue (BAT), white adipose (WAT) and liver of mice in response to 24 h cold exposure at 8°C. Expression of 1895 genes were significantly (P<0.05) up- or down-regulated more than two fold by cold exposure in all tissues but only 5 of these genes were shared by all three tissues, and only 19, 14 and 134 genes were common between WAT and BAT, WAT and liver, and BAT and liver, respectively. We confirmed using qRT-PCR, the increased expression of a number of characteristic BAT genes during cold exposure. In both BAT and the liver, the most common direction of change in gene expression was suppression (496 genes in BAT and 590 genes in liver). Gene ontology analysis revealed for the first time significant (P<0.05) down regulation in response to cold, of genes involved in oxidoreductase activity, lipid metabolic processes and protease inhibitor activity, in both BAT and liver, but not WAT. The results reveal an unexpected importance of down regulation of cytochrome P450 gene expression and apolipoprotein, in both BAT and liver, but not WAT, in response to cold exposure. Pathway analysis suggests a model in which down regulation of the nuclear transcription factors HNF4α and PPARα in both BAT and liver may orchestrate the down regulation of genes involved in lipoprotein and steroid metabolism as well as Phase I enzymes belonging to the cytochrome P450 group in response to cold stress in mice. We propose that the response to cold stress involves decreased gene expression in a range of cellular processes in order to maximise pathways involved in heat production. PMID:23894377

The impact of banners on digital television: the role of program interactivity and product involvement.

PubMed

Cauberghe, Verolien; De Pelsmacker, Patrick

2008-02-01

In a sample of 281 respondents, the effect of a noninteractive and a medium-interactive television program on recall and brand attitudes for low- and high-involvement products advertised in banners during these programs was investigated. Medium-interactive programs resulted in less product and brand recall and recognition of brands in embedded banner advertisements, but generated more positive brand attitudes than noninteractive programs. These effects were more outspoken for a high-involvement product than for a low-involvement product. The impact of perceived program interactivity on brand attitude is fully mediated program valence and involvement for low-involvement products, but not for high-involvement products, for which perceived program interactivity had a direct impact on brand attitude.

Transcriptome response signatures associated with the overexpression of a mitochondrial uncoupling protein (AtUCP1) in tobacco.

PubMed

Laitz, Alessandra Vasconcellos Nunes; Acencio, Marcio Luis; Budzinski, Ilara G F; Labate, Mônica T V; Lemke, Ney; Ribolla, Paulo Eduardo Martins; Maia, Ivan G

2015-01-01

Mitochondrial inner membrane uncoupling proteins (UCP) dissipate the proton electrochemical gradient established by the respiratory chain, thus affecting the yield of ATP synthesis. UCP overexpression in plants has been correlated with oxidative stress tolerance, improved photosynthetic efficiency and increased mitochondrial biogenesis. This study reports the main transcriptomic responses associated with the overexpression of an UCP (AtUCP1) in tobacco seedlings. Compared to wild-type (WT), AtUCP1 transgenic seedlings showed unaltered ATP levels and higher accumulation of serine. By using RNA-sequencing, a total of 816 differentially expressed genes between the investigated overexpressor lines and the untransformed WT control were identified. Among them, 239 were up-regulated and 577 were down-regulated. As a general response to AtUCP1 overexpression, noticeable changes in the expression of genes involved in energy metabolism and redox homeostasis were detected. A substantial set of differentially expressed genes code for products targeted to the chloroplast and mainly involved in photosynthesis. The overall results demonstrate that the alterations in mitochondrial function provoked by AtUCP1 overexpression require important transcriptomic adjustments to maintain cell homeostasis. Moreover, the occurrence of an important cross-talk between chloroplast and mitochondria, which culminates in the transcriptional regulation of several genes involved in different pathways, was evidenced.

Approaches to Mitigate the Unwanted Immunogenicity of Therapeutic Proteins during Drug Development.

PubMed

Salazar-Fontana, Laura I; Desai, Dharmesh D; Khan, Tarik A; Pillutla, Renuka C; Prior, Sandra; Ramakrishnan, Radha; Schneider, Jennifer; Joseph, Alexandra

2017-03-01

All biotherapeutics have the potential to induce an immune response. This immunological response is complex and, in addition to antibody formation, involves T cell activation and innate immune responses that could contribute to adverse effects. Integrated immunogenicity data analysis is crucial to understanding the possible clinical consequences of anti-drug antibody (ADA) responses. Because patient- and product-related factors can influence the immunogenicity of a therapeutic protein, a risk-based approach is recommended and followed by most drug developers to provide insight over the potential harm of unwanted ADA responses. This paper examines mitigation strategies currently implemented and novel under investigation approaches used by drug developers. The review describes immunomodulatory regimens used in the clinic to mitigate deleterious ADA responses to replacement therapies for deficiency syndromes, such as hemophilia A and B, and high risk classical infantile Pompe patients (e.g., cyclophosphamide, methotrexate, rituximab); novel in silico and in vitro prediction tools used to select candidates based on their immunogenicity potential (e.g., anti-CD52 antibody primary sequence and IFN beta-1a formulation); in vitro generation of tolerogenic antigen-presenting cells (APCs) to reduce ADA responses to factor VIII and IX in murine models of hemophilia; and selection of novel delivery systems to reduce in vivo ADA responses to highly immunogenic biotherapeutics (e.g., asparaginase). We conclude that mitigation strategies should be considered early in development for biotherapeutics based on our knowledge of existing clinical data for biotherapeutics and the immune response involved in the generation of these ADAs.

Genomics Approaches For Improving Salinity Stress Tolerance in Crop Plants.

PubMed

Nongpiur, Ramsong Chantre; Singla-Pareek, Sneh Lata; Pareek, Ashwani

2016-08-01

Salinity is one of the major factors which reduces crop production worldwide. Plant responses to salinity are highly complex and involve a plethora of genes. Due to its multigenicity, it has been difficult to attain a complete understanding of how plants respond to salinity. Genomics has progressed tremendously over the past decade and has played a crucial role towards providing necessary knowledge for crop improvement. Through genomics, we have been able to identify and characterize the genes involved in salinity stress response, map out signaling pathways and ultimately utilize this information for improving the salinity tolerance of existing crops. The use of new tools, such as gene pyramiding, in genetic engineering and marker assisted breeding has tremendously enhanced our ability to generate stress tolerant crops. Genome editing technologies such as Zinc finger nucleases, TALENs and CRISPR/Cas9 also provide newer and faster avenues for plant biologists to generate precisely engineered crops.

Carcinoembryonic antigen induces signal transduction in Kupffer cells.

PubMed

Gangopadhyay, A; Lazure, D A; Thomas, P

1997-09-16

Carcinoembryonic antigen (CEA), an intercellular adhesion molecule and a mediator of hepatic metastasis, is processed by an 80 kDa receptor on murine and human Kupffer cells in the liver. Activation of rat Kupffer cells in vitro by CEA via the 80 kDa receptor produced cytokines IL-1alpha and TNF-alpha which involved tyrosine phosphorylation. The peak response of TNF-alpha was 5.6 times greater than the corresponding IL-1alpha response and was associated with enhanced tyrosine phosphorylation of 108 and 125 kDa proteins. Lipopolysaccharide (LPS) treatment, on the other hand, phosphorylated two major proteins with MW of 93 and 119 kDa associated with the loss of phosphorylation from a 125 kDa protein. Results demonstrate that CEA-induced IL-1alpha and TNF-alpha production involves tyrosine phosphorylation and the signaling in CEA treated cells is different than that seen with LPS stimulation.

Cell Density Control of Staphylococcal Virulence Mediated by an Octapeptide Pheromone

NASA Astrophysics Data System (ADS)

Ji, Guangyong; Beavis, Ronald C.; Novick, Richard P.

1995-12-01

Some bacterial pathogens elaborate and secrete virulence factors in response to environmental signals, others in response to a specific host product, and still others in response to no discernible cue. In this study, we have demonstrated that the synthesis of Staphylococcus aureus virulence factors is controlled by a density-sensing system that utilizes an octapeptide produced by the organism itself. The octapeptide activates expression of the agr locus, a global regulator of the virulence response. This response involves the reciprocal regulation of genes encoding surface proteins and those encoding secreted virulence factors. As cells enter the postexponential phase, surface protein genes are repressed by agr and secretory protein genes are subsequently activated. The intracellular agr effector is a regulatory RNA, RNAIII, whose transcription is activated by an agr-encoded signal transduction system for which the octapeptide is the ligand.

Effect of exercise training on ventilatory efficiency in patients with heart disease: a review.

PubMed

Prado, D M L; Rocco, E A; Silva, A G; Rocco, D F; Pacheco, M T; Furlan, V

2016-06-20

The analysis of ventilatory efficiency in cardiopulmonary exercise testing has proven useful for assessing the presence and severity of cardiorespiratory diseases. During exercise, efficient pulmonary gas exchange is characterized by uniform matching of lung ventilation with perfusion. By contrast, mismatching is marked by inefficient pulmonary gas exchange, requiring increased ventilation for a given CO2 production. The etiology of increased and inefficient ventilatory response to exercise in heart disease is multifactorial, involving both peripheral and central mechanisms. Exercise training has been recommended as non-pharmacological treatment for patients with different chronic cardiopulmonary diseases. In this respect, previous studies have reported improvements in ventilatory efficiency after aerobic exercise training in patients with heart disease. Against this background, the primary objective of the present review was to discuss the pathophysiological mechanisms involved in abnormal ventilatory response to exercise, with an emphasis on both patients with heart failure syndrome and coronary artery disease. Secondly, special focus was dedicated to the role of aerobic exercise training in improving indices of ventilatory efficiency among these patients, as well as to the underlying mechanisms involved.

Yeast as a model for Ras signalling.

PubMed

Tisi, Renata; Belotti, Fiorella; Martegani, Enzo

2014-01-01

For centuries yeast species have been popular hosts for classical biotechnology processes, such as baking, brewing, and wine making, and more recently for recombinant proteins production, thanks to the advantages of unicellular organisms (i.e., ease of genetic manipulation and rapid growth) together with the ability to perform eukaryotic posttranslational modifications. Moreover, yeast cells have been used for few decades as a tool for identifying the genes and pathways involved in basic cellular processes such as the cell cycle, aging, and stress response. In the budding yeast S. cerevisiae the Ras/cAMP/PKA pathway is directly involved in the regulation of metabolism, cell growth, stress resistance, and proliferation in response to the availability of nutrients and in the adaptation to glucose, controlling cytosolic cAMP levels and consequently the cAMP-dependent protein kinase (PKA) activity. Moreover, Ras signalling has been identified in several pathogenic yeasts as a key controller for virulence, due to its involvement in yeast morphogenesis. Nowadays, yeasts are still useful for Ras-like proteins investigation, both as model organisms and as a test tube to study variants of heterologous Ras-like proteins.

The Role of COX-2 in the Inflammatory and Fibrotic Response in the Lung Following Exposure to Multi-Walled Carbon Nanotubes

NASA Astrophysics Data System (ADS)

Sayers, Brian C.

Exposure to multiwalled carbon nanotubes (MWCNT) has been demonstrated to exacerbate airway inflammation and fibrosis in allergen-challenged mouse model. These data have led to concern that individuals with asthma could represent a susceptible population to adverse health effects following exposure to MWCNT, and possibly other engineered nanoparticles. Asthma pathogenesis is caused by the interaction of a complex genetic predisposition and environmental exposures. Because chronic airway inflammation is common to all asthma phenotypes, it is logical to investigate genes that are involved in inflammatory pathways in order to understand the genetic basis of asthma. The metabolism of arachidonic acid by cyclooxygenase (COX) enzymes is the rate-determining step in the synthesis of prostanoids, which are biologically active lipids that are important modulators of inflammation. Based on the role of COX enzymes in inflammatory pathways, we sought to investigate how COX enzymes are involved in the inflammatory response following MWCNT exposure in asthmatic airways. We report that MWCNT significantly exacerbated allergen-induced airway inflammation and mucus cell metaplasia in COX-2 deficient mice compared to wild type mice. In addition, MWCNTs significantly enhanced allergen-induced cytokines involved in Th2 (IL-13, IL-5), Th1 (CXCL10), and Th17 (IL-17A) inflammatory responses in COX-2 deficient mice but not in WT mice. We conclude that exacerbation of allergen-induced airway inflammation and mucus cell metaplasia by MWCNTs is enhanced by deficiency in COX-2 and associated with activation of a mixed Th1/Th2/Th17 immune response. Based on our observation that COX-2 deficient mice developed a mixed Th immune response following MWCNT exposure, we sought to evaluate how cytokines associated with different Th immune responses alter COX expression following MWCNT exposure. For this study, a mouse macrophage cell line (RAW264.7) was used because MWCNT were largely sequestered within alveolar macrophages with 24 hours after aspiration in mice. We report that the Th1 cytokine interferon gamma (IFNgamma) causes decreased COX-1 expression but increased prostaglandin E2 (PGE 2) production in mouse macrophages exposed to nickel nanoparticles (NiNP), a residual impurity found in MWCNT from the catalytic synthesis process. NiNP exposure alone increased COX-2 and decreased COX-1 in the absence of exogenous cytokines. IFNgamma further reduced COX-1 levels suppressed by NiNP. IL-4, IL-13, or IL-17 did not reduce COX-1 expression alone or in combination with NiNP. Exogenous PGE2 enhanced NiNP- or IFN-gamma-mediated COX-1 suppression. Pharmacologic inhibition of ERK1,2 or JAK/STAT-1 cell signaling pathways inhibited PGE2 production in all dose groups and restored COX-1 expression in cells treated with IFNgamma and NiNP. These data show that PGE2 production is induced in macrophages exposed to IFNgamma and NiNP and suggest that macrophages could be an important source of the anti-inflammatory mediator PGE2 following nanoparticle exposure in a Th1 immune microenvironment. In summary, these studies highlight an important role for COX enzymes in regulating inflammation in response to engineered nanoparticles and show that prostanoid production in response to nanoparticle exposure could be determined in part by the Th immune microenvironment.

Transcriptome profiling analysis of senescent gingival fibroblasts in response to Fusobacterium nucleatum infection

PubMed Central

Ahn, Sun-Hee; Chun, Sung-Min; Park, Chungoo; Lee, Jong-Hee; Lee, Seok-Woo

2017-01-01

Periodontal disease is caused by dental plaque biofilms. Fusobacterium nucleatum is an important periodontal pathogen involved in the development of bacterial complexity in dental plaque biofilms. Human gingival fibroblasts (GFs) act as the first line of defense against oral microorganisms and locally orchestrate immune responses by triggering the production of reactive oxygen species and pro-inflammatory cytokines (IL-6 and IL-8). The frequency and severity of periodontal diseases is known to increase in elderly subjects. However, despite several studies exploring the effects of aging in periodontal disease, the underlying mechanisms through which aging affects the interaction between F. nucleatum and human GFs remain unclear. To identify genes affected by infection, aging, or both, we performed an RNA-Seq analysis using GFs isolated from a single healthy donor that were passaged for a short period of time (P4) ‘young GFs’ or for longer period of time (P22) ‘old GFs’, and infected or not with F. nucleatum. Comparing F. nucleatum-infected and uninfected GF(P4) cells the differentially expressed genes (DEGs) were involved in host defense mechanisms (i.e., immune responses and defense responses), whereas comparing F. nucleatum-infected and uninfected GF(P22) cells the DEGs were involved in cell maintenance (i.e., TGF-β signaling, skeletal development). Most DEGs in F. nucleatum-infected GF(P22) cells were downregulated (85%) and were significantly associated with host defense responses such as inflammatory responses, when compared to the DEGs in F. nucleatum-infected GF(P4) cells. Five genes (GADD45b, KLF10, CSRNP1, ID1, and TM4SF1) were upregulated in response to F. nucleatum infection; however, this effect was only seen in GF(P22) cells. The genes identified here appear to interact with each other in a network associated with free radical scavenging, cell cycle, and cancer; therefore, they could be potential candidates involved in the aged GF’s response to F. nucleatum infection. Further studies are needed to confirm these observations. PMID:29190775

Transfer Functions Via Laplace- And Fourier-Borel Transforms

NASA Technical Reports Server (NTRS)

Can, Sumer; Unal, Aynur

1991-01-01

Approach to solution of nonlinear ordinary differential equations involves transfer functions based on recently-introduced Laplace-Borel and Fourier-Borel transforms. Main theorem gives transform of response of nonlinear system as Cauchy product of transfer function and transform of input function of system, together with memory effects. Used to determine responses of electrical circuits containing variable inductances or resistances. Also possibility of doing all noncommutative algebra on computers in such symbolic programming languages as Macsyma, Reduce, PL1, or Lisp. Process of solution organized and possibly simplified by algebraic manipulations reducing integrals in solutions to known or tabulated forms.

An Empirical Study of the Volkswagen Crisis in China: Customers' Information Processing and Behavioral Intentions.

PubMed

Wei, Jiuchang; Zhao, Ming; Wang, Fei; Cheng, Peng; Zhao, Dingtao

2016-01-01

Product-harm crises usually lead to product recalls, which may cause consumers concern about the product quality and safety. This study systematically examines customers' immediate responses to the Volkswagen product recall crisis in China. Particular attention was given to customers' responses to the risk information influencing their behavioral intentions. By combining the protective action decision model and the heuristic-systematic model, we constructed a hypothetical model to explore this issue. A questionnaire survey was conducted to collect data involving 467 participants drawn from the customers of Volkswagen. We used structural equation modeling to explore the model. The results show that customers' product knowledge plays an important role in their responses to the crisis. Having more knowledge would make them perceive a lower risk, but they might need even more information, making them more likely to seek and process information, and subsequently increasing their positive behavioral intentions toward the firm (that is pro-firm behavioral intentions). Risk perception increased customers' information needs, information seeking, and information processing but decreased their pro-firm behavioral intentions. In addition to promoting information seeking, information needed to also facilitate customers' systematic processing and thus increase their behavioral intentions to take corrective action. Customers' behavioral intentions were also spurred by systematic processing, but failed to be predicted by information seeking. In summary, theoretical and practical implications and suggestions for further research are also discussed. © 2015 Society for Risk Analysis.

Metabolomic and Proteomic Insights into Carbaryl Catabolism by Burkholderia sp. C3 and Degradation of Ten N-Methylcarbamates

PubMed Central

Seo, Jong-Su; Keum, Young-Soo; Li, Qing X.

2013-01-01

Burkholderia sp. C3, an efficient polycyclic aromatic hydrocarbon (PAH) degrader, can utilize 9 of the 10 N-methylcarbamate insecticides including carbaryl as a sole source of carbon. Rapid hydrolysis of carbaryl in C3 is followed by slow catabolism of the resulting 1-naphthol. This study focused on metabolomes and proteomes in C3 cells utilizing carbaryl in comparison to those using glucose or nutrient broth. Sixty of the 867 detected proteins were involved in primary metabolism, adaptive sensing and regulation, transport, stress response, and detoxification. Among the 41 proteins expressed in response to carbaryl were formate dehydrogenase, aldehyde-alcohol dehydrogenase and ethanolamine utilization protein involved in one carbon metabolism. Acetate kinase and phasin were 2 of the 19 proteins that were not detected in carbaryl-supported C3 cells, but detected in glucose-supported C3 cells. Down-production of phasin and polyhydroxyalkanoates in carbaryl-supported C3 cells suggests insufficient carbon sources and lower levels of primary metabolites to maintain an ordinary level of metabolism. Differential metabolomes (approximately 196 identified polar metabolites) showed up-production of metabolites in pentose phosphate pathways and metabolisms of cysteine, cystine and some other amino acids, disaccharides and nicotinate, in contract to down-production of most of the other amino acids and hexoses. The proteomic and metabolomic analyses showed that carbaryl-supported C3 cells experienced strong toxic effects, oxidative stresses, DNA/RNA damages and carbon nutrient deficiency. PMID:23463356

Necroptosis promotes cell-autonomous activation of proinflammatory cytokine gene expression.

PubMed

Zhu, Kezhou; Liang, Wei; Ma, Zaijun; Xu, Daichao; Cao, Shuangyi; Lu, Xiaojuan; Liu, Nan; Shan, Bing; Qian, Lihui; Yuan, Junying

2018-04-27

Necroptosis, a form of regulated necrotic cell death, is mediated by receptor interacting protein 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL). However, the mechanism by which necroptosis promotes inflammation is still unclear. Here we report that the expression of cytokines is robustly upregulated in a cell-autonomous manner during necroptosis induced by tumor necrosis factor alpha (TNFα). We demonstrate that TNFα-induced necroptosis leads to two waves of cytokine production. The first wave, more transient and weaker than the second, is in response to TNFα alone; whereas the second wave depends upon the necroptotic signaling. We show that necroptosis promotes the transcription of TNFα-target genes in a cell-intrinsic manner. The activation of both NF-κB and p38 by the necroptotic machinery, RIPK1, RIPK3, and MLKL, is involved in mediating the robust induction of cytokine expression in the second wave. In contrast, necroptosis induced by direct oligomerization of MLKL promotes cytokine production at much lower levels than that of necroptosis induced with TNFα. Thus, we conclude that TNFα-induced necroptosis signaling events mediated by RIPK1 and RIPK3 activation, in addition to the MLKL oligomerization, promotes the expression of cytokines involving multiple intracellular signaling mechanisms including NF-κB pathway and p38. These findings reveal that the necroptotic cell death machinery mounts an immune response by promoting cell-autonomous production of cytokines. Our study provides insights into the mechanism by which necroptosis promotes inflammation in human diseases.

Challenges for a Sustainable Financial Foundation for Antimicrobial Stewardship.

PubMed

Dik, Jan-Willem H; Sinha, Bhanu

2017-03-30

Antimicrobial resistance is a worldwide threat and a problem with large clinical and economic impact. Antimicrobial Stewardship Programs are a solution to curb resistance development. A problem of resistance is a separation of actions and consequences, financial and clinical. Such a separation makes it difficult to create support among stakeholders leading to a lack of sense of responsibility. To counteract the resistance development it is important to perform diagnostics and know how to interpret the results. One should see diagnostics, therapy and resistance as one single process. Within this process all involved stakeholders need to work together on a more institutional level. We suggest therefore a solution: combining diagnostics and therapy into one single financial product . Such a product should act as an incentive to perform correct diagnostics. It also makes it easier to cover the costs of an antimicrobial stewardship program, which is often overlooked. Finally, such a product involves all stakeholders in the process and does not lay the costs at one stakeholder and the benefits somewhere else, solving the misbalance that is present nowadays.

Leptospira santorosai Serovar Shermani detergent extract induces an increase in fibronectin production through a Toll-like receptor 2-mediated pathway.

PubMed

Tian, Ya-Chung; Hung, Cheng-Chieh; Li, Yi-Jung; Chen, Yung-Chang; Chang, Ming-Yang; Yen, Tzung-Hai; Hsu, Hsiang-Hao; Wu, Mai-Szu; Phillips, Aled; Yang, Chih-Wei

2011-03-01

Leptospirosis can activate inflammatory responses through Toll-like receptors (TLRs) and may cause renal tubulointerstitial fibrosis characterized by the accumulation of extracellular matrix (ECM). We have previously demonstrated that Leptospira santorosai serovar Shermani detergent extract stimulates ECM accumulation in vitro. The aim of this study was to examine the mechanistic basis of these previous observations and, in particular, to examine the potential involvement of TLRs. The addition of serovar Shermani detergent extract led to an increase in fibronectin gene expression and production. Inhibition of TLR2 but not TLR4 expression abrogated serovar Shermani detergent extract-mediated increases in fibronectin production. This response was also blocked by the knockdown of the gene expression of the TLR2 downstream transducers myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6). Serovar Shermani detergent extract also activated nuclear factor-κB, and its inhibition by curcumin-attenuated serovar Shermani detergent extract induced increases in fibronectin production. These effects were also mimicked by the specific TLR2 agonist, Pam(3)CsK(4), a response that was also abrogated by the knockdown of MyD88 and TRAF6. Similarly, the administration of live leptospires to cells also induced fibronectin production that was blocked by inhibition of TLR2 and MyD88 expression. In conclusion, serovar Shermani detergent extract can induce fibronectin production through the TLR2-associated cascade, providing evidence of an association between TLRs and leptospirosis-mediated ECM deposition.

Development of an in vitro photosafety evaluation method utilizing intracellular ROS production in THP-1 cells.

PubMed

Toyoda, Akemi; Itagaki, Hiroshi

2018-01-01

Photoreactive compounds that may experience exposure to ultraviolet (UV) radiation can lead to the intracellular production of reactive oxygen species (ROS), which may cause phototoxic and photoallergenic responses. Here, we developed a novel in vitro photosafety assay and investigated whether it could be used to predict phototoxicity and photosensitivity by measuring changes in intracellular ROS production. THP-1 cells that had previously taken up 5-(and-6)-carboxy-2',7'-difluorodihydrofluorescein diacetate (carboxy-H 2 DFFDA), a ROS-sensitive fluorescent reagent, were exposed to photoreactive substances such as phototoxic and photoallergenic materials and then subjected to with UV-A irradiation (5 J/cm 2 ). The fluorescence intensity was subsequently measured using a flow cytometer, and the intracellular ROS production was calculated. A statistically significant increase in ROS following treatment with photoreactive substances was observed in cells irradiated with UV-A. In contrast, no significant increase was observed for non-photoreactive substances in comparison to the control solution. Next, to confirm the impact of intracellular ROS on the photosensitive response, changes in CD86 and CD54 expression were measured following quencher addition during the photo human cell line activation test (photo h-CLAT). The results confirmed the reduction of CD86 and CD54 expression in response to photoallergenic substances following quencher addition. Together, these findings suggest that intracellular ROS production is involved in photosensitizing reactions. Therefore, we suggest that the developed method utilizing intracellular ROS production as an index may be useful as a novel in vitro evaluation tool for photoreactive substances.

The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

PubMed Central

Jeschke, Marc G

2009-01-01

Thermal injury produces a profound hypermetabolic and hypercatabolic stress response characterized by increased endogenous glucose production via gluconeogenesis and glycogenolysis, lipolysis, and proteolysis. The liver is the central body organ involved in these metabolic responses. It is suggested that the liver, with its metabolic, inflammatory, immune, and acute phase functions, plays a pivotal role in patient survival and recovery by modulating multiple pathways following thermal injury. Studies have evaluated the role and function of the liver during the postburn response and showed that liver integrity and function are essential for survival, and that hepatic acute phase proteins are strong predictors for postburn survival. This review discusses these studies and delineates the pivotal role of the liver in patients following severe thermal injury. PMID:19603107

The response to unfolded protein is involved in osmotolerance of Pichia pastoris

PubMed Central

2010-01-01

Background The effect of osmolarity on cellular physiology has been subject of investigation in many different species. High osmolarity is of importance for biotechnological production processes, where high cell densities and product titers are aspired. Several studies indicated that increased osmolarity of the growth medium can have a beneficial effect on recombinant protein production in different host organisms. Thus, the effect of osmolarity on the cellular physiology of Pichia pastoris, a prominent host for recombinant protein production, was studied in carbon limited chemostat cultures at different osmolarities. Transcriptome and proteome analyses were applied to assess differences upon growth at different osmolarities in both, a wild type strain and an antibody fragment expressing strain. While our main intention was to analyze the effect of different osmolarities on P. pastoris in general, this was complemented by studying it in context with recombinant protein production. Results In contrast to the model yeast Saccharomyces cerevisiae, the main osmolyte in P. pastoris was arabitol rather than glycerol, demonstrating differences in osmotic stress response as well as energy metabolism. 2D Fluorescence Difference Gel electrophoresis and microarray analysis were applied and demonstrated that processes such as protein folding, ribosome biogenesis and cell wall organization were affected by increased osmolarity. These data indicated that upon increased osmolarity less adaptations on both the transcript and protein level occurred in a P. pastoris strain, secreting the Fab fragment, compared with the wild type strain. No transcriptional activation of the high osmolarity glycerol (HOG) pathway was observed at steady state conditions. Furthermore, no change of the specific productivity of recombinant Fab was observed at increased osmolarity. Conclusion These data point out that the physiological response to increased osmolarity is different to S. cerevisiae. Increased osmolarity resulted in an unfolded protein response (UPR) like response in P. pastoris and lead to pre-conditioning of the recombinant Fab producing strain of P. pastoris to growth at high osmolarity. The current data demonstrate a strong similarity of environmental stress response mechanisms and recombinant protein related stresses. Therefore, these results might be used in future strain and bioprocess engineering of this biotechnologically relevant yeast. PMID:20346137

Specificity of anti-Vibrio immune response through p38 MAPK and PKC activation in the hemocytes of the mussel Mytilus galloprovincialis.

PubMed

Ciacci, Caterina; Betti, Michele; Canonico, Barbara; Citterio, Barbara; Roch, Philippe; Canesi, Laura

2010-09-01

In mussel (Mytilus sp.) hemocytes, differential functional responses to injection with different types of live and heat-killed Vibrio species have been recently demonstrated. In this work, responses of Mytilus hemocytes to heat-killed Vibrio splendidus LGP32 and the mechanisms involved were investigated in vitro and the results were compared with those obtained with Vibrio anguillarum (ATCC 19264). Adhesion of hemocytes after incubation with bacteria was evaluated by flow cytometry: both total hemocyte counts (THC) and percentage of hemocyte sub-populations were determined in non-adherent cells. Functional parameters such as lysosomal membrane stability, lysozyme release, extracellular ROS production and NO production were evaluated, as well as the phosphorylation state of the stress-activated p38 MAPK and PKC. Neither Vibrio affected total hemocyte adhesion, while both induced similar lysosomal destabilization and NO production. However, V. splendidus decreased adhesion of large granulocytes, induced rapid and persistent lysozyme release and stimulated extracellular ROS production: these effects were associated with persistent activation of p38 MAPK and PKC. In contrast, V. anguillarum decreased adhesion of large semigranular hemocytes and increased that of hyalinocytes, had no effect on the extracellular ROS production, and induced significantly lower lysozyme release and phosphorylation of p-38 MAPK and PKC than V. splendidus. These data reinforced the existence of specific interactions between mussel hemocytes and V. splendidus LGP32 and suggest that this Vibrio strain affects bivalve hemocytes through disregulation of immune signaling. The results support the hypothesis that responses of bivalve hemocytes to different bacterial stimuli may depend not only on the nature of the stimulus, but also on the cell subtype, thus leading to differential activation of signaling components. Copyright 2010 Elsevier Inc. All rights reserved.

Critical role of type 1 cytokines in controlling initial infection with Burkholderia mallei.

PubMed

Rowland, Caroline A; Lertmemongkolchai, Ganjana; Bancroft, Alison; Haque, Ashraful; Lever, M Stephen; Griffin, Kate F; Jackson, Matthew C; Nelson, Michelle; O'Garra, Anne; Grencis, Richard; Bancroft, Gregory J; Lukaszewski, Roman A

2006-09-01

Burkholderia mallei is a gram-negative bacterium which causes the potentially fatal disease glanders in humans; however, there is little information concerning cell-mediated immunity to this pathogen. The role of gamma interferon (IFN-gamma) during B. mallei infection was investigated using a disease model in which infected BALB/c mice normally die between 40 and 60 days postinfection. IFN-gamma knockout mice infected with B. mallei died within 2 to 3 days after infection, and there was uncontrolled bacterial replication in several organs, demonstrating the essential role of IFN-gamma in the innate immune response to this pathogen. Increased levels of IFN-gamma, interleukin-6 (IL-6), and monocyte chemoattractant protein 1 were detected in the sera of immunocompetent mice in response to infection, and splenic mRNA expression of IFN-gamma, IL-6, IL-12p35, and IL-27 was elevated 24 h postinfection. The effects of IL-18, IL-27, and IL-12 on stimulation of the rapid IFN-gamma production were investigated in vitro by analyzing IFN-gamma production in the presence of heat-killed B. mallei. IL-12 was essential for IFN-gamma production in vitro; IL-18 was also involved in induction of IFN-gamma, but IL-27 was not required for IFN-gamma production in response to heat-killed B. mallei. The main cellular sources of IFN-gamma were identified in vitro as NK cells, CD8+ T cells, and TCRgammadelta T cells. Our data show that B. mallei is susceptible to cell-mediated immune responses which promote expression of type 1 cytokines. This suggests that development of effective vaccines against glanders should target the production of IFN-gamma.

Trichoderma Biocontrol: Signal Transduction Pathways Involved in Host Sensing and Mycoparasitism

PubMed Central

Zeilinger, Susanne; Omann, Markus

2007-01-01

Fungi of the genus Trichoderma are used as biocontrol agents against several plant pathogenic fungi like Rhizoctonia spp., Pythium spp., Botrytis cinerea and Fusarium spp. which cause both soil-borne and leaf- or flower-borne diseases of agricultural plants. Plant disease control by Trichoderma is based on complex interactions between Trichoderma, the plant pathogen and the plant. Until now, two main components of biocontrol have been identified: direct activity of Trichoderma against the plant pathogen by mycoparasitism and induced systemic resistance in plants. As the mycoparasitic interaction is host-specific and not merely a contact response, it is likely that signals from the host fungus are recognised by Trichoderma and provoke transcription of mycoparasitism-related genes. In the last few years examination of signalling pathways underlying Trichoderma biocontrol started and it was shown that heterotrimeric G-proteins and mitogen-activated protein (MAP) kinases affected biocontrol-relevant processes such as the production of hydrolytic enzymes and antifungal metabolites and the formation of infection structures. MAPK signalling was also found to be involved in induction of plant systemic resistance in Trichoderma virens and in the hyperosmotic stress response in Trichoderma harzianum. Analyses of the function of components of the cAMP pathway during Trichoderma biocontrol revealed that mycoparasitism-associated coiling and chitinase production as well as secondary metabolism are affected by the internal cAMP level; in addition, a cross talk between regulation of light responses and the cAMP signalling pathway was found in Trichoderma atroviride. PMID:19936091

Trichoderma biocontrol: signal transduction pathways involved in host sensing and mycoparasitism.

PubMed

Zeilinger, Susanne; Omann, Markus

2007-11-08

Fungi of the genus Trichoderma are used as biocontrol agents against several plant pathogenic fungi like Rhizoctonia spp., Pythium spp., Botrytis cinerea and Fusarium spp. which cause both soil-borne and leaf- or flower-borne diseases of agricultural plants. Plant disease control by Trichoderma is based on complex interactions between Trichoderma, the plant pathogen and the plant. Until now, two main components of biocontrol have been identified: direct activity of Trichoderma against the plant pathogen by mycoparasitism and induced systemic resistance in plants. As the mycoparasitic interaction is host-specific and not merely a contact response, it is likely that signals from the host fungus are recognised by Trichoderma and provoke transcription of mycoparasitism-related genes. In the last few years examination of signalling pathways underlying Trichoderma biocontrol started and it was shown that heterotrimeric G-proteins and mitogen-activated protein (MAP) kinases affected biocontrol-relevant processes such as the production of hydrolytic enzymes and antifungal metabolites and the formation of infection structures. MAPK signalling was also found to be involved in induction of plant systemic resistance in Trichoderma virens and in the hyperosmotic stress response in Trichoderma harzianum. Analyses of the function of components of the cAMP pathway during Trichoderma biocontrol revealed that mycoparasitism-associated coiling and chitinase production as well as secondary metabolism are affected by the internal cAMP level; in addition, a cross talk between regulation of light responses and the cAMP signalling pathway was found in Trichoderma atroviride.

A designed screening study with prespecified combinations of factor settings

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

Anderson-cook, Christine M; Robinson, Timothy J

2009-01-01

In many applications, the experimenter has limited options about what factor combinations can be chosen for a designed study. Consider a screening study for a production process involving five input factors whose levels have been previously established. The goal of the study is to understand the effect of each factor on the response, a variable that is expensive to measure and results in destruction of the part. From an inventory of available parts with known factor values, we wish to identify a best collection of factor combinations with which to estimate the factor effects. Though the observational nature of themore » study cannot establish a causal relationship involving the response and the factors, the study can increase understanding of the underlying process. The study can also help determine where investment should be made to control input factors during production that will maximally influence the response. Because the factor combinations are observational, the chosen model matrix will be nonorthogonal and will not allow independent estimation of factor effects. In this manuscript we borrow principles from design of experiments to suggest an 'optimal' selection of factor combinations. Specifically, we consider precision of model parameter estimates, the issue of replication, and abilities to detect lack of fit and to estimate two-factor interactions. Through an example, we present strategies for selecting a subset of factor combinations that simultaneously balance multiple objectives, conduct a limited sensitivity analysis, and provide practical guidance for implementing our techniques across a variety of quality engineering disciplines.« less

Transcriptional Profiling of the Oral Pathogen Streptococcus mutans in Response to Competence Signaling Peptide XIP.

PubMed

Wenderska, Iwona B; Latos, Andrew; Pruitt, Benjamin; Palmer, Sara; Spatafora, Grace; Senadheera, Dilani B; Cvitkovitch, Dennis G

2017-01-01

In the cariogenic Streptococcus mutans , competence development is regulated by the ComRS signaling system comprised of the ComR regulator and the ComS prepeptide to the competence signaling peptide XIP (ComX-inducing peptide). Aside from competence development, XIP signaling has been demonstrated to regulate cell lysis, and recently, the expression of bacteriocins, small antimicrobial peptides used by bacteria to inhibit closely related species. Our study further explores the effect of XIP signaling on the S. mutans transcriptome. RNA sequencing revealed that XIP induction resulted in a global change in gene expression that was consistent with a stress response. An increase in several membrane-bound regulators, including HdrRM and BrsRM, involved in bacteriocin production, and the VicRKX system, involved in acid tolerance and biofilm formation, was observed. Furthermore, global changes in gene expression corresponded to changes observed during the stringent response to amino acid starvation. Effects were also observed on genes involved in sugar transport and carbon catabolite repression and included the levQRST and levDEFG operons. Finally, our work identified a novel heat shock-responsive intergenic region, encoding a small RNA, with a potential role in competence shutoff. IMPORTANCE Genetic competence provides bacteria with an opportunity to increase genetic diversity or acquire novel traits conferring a survival advantage. In the cariogenic pathogen Streptococcus mutans , DNA transformation is regulated by the competence stimulating peptide XIP (ComX-inducing peptide). The present study utilizes high-throughput RNA sequencing (RNAseq) to provide a greater understanding of how global gene expression patterns change in response to XIP. Overall, our work demonstrates that in S. mutans , XIP signaling induces a response that resembles the stringent response to amino acid starvation. We further identify a novel heat shock-responsive intergenic region with a potential role in competence shutoff. Together, our results provide further evidence that multiple stress response mechanisms are linked through the genetic competence signaling pathway in S. mutans .

Perceptions of Health Communication, Water Treatment and Sanitation in Artibonite Department, Haiti, March-April 2012

PubMed Central

Williams, Holly Ann; Gaines, Joanna; Patrick, Molly; Berendes, David; Fitter, David; Handzel, Thomas

2015-01-01

The international response to Haiti’s ongoing cholera outbreak has been multifaceted, including health education efforts by community health workers and the distribution of free water treatment products. Artibonite Department was the first region affected by the outbreak. Numerous organizations have been involved in cholera response efforts in Haiti with many focusing on efforts to improve water, sanitation, and hygiene (WASH). Multiple types of water treatment products have been distributed, creating the potential for confusion over correct dosage and water treatment methods. We utilized qualitative methods in Artibonite to determine the population’s response to WASH messages, use and acceptability of water treatment products, and water treatment and sanitation knowledge, attitudes and practices at the household level. We conducted eighteen focus group discussions (FGDs): 17 FGDs were held with community members (nine among females, eight among males); one FGD was held with community health workers. Health messages related to WASH were well-retained, with reported improvements in hand-washing. Community health workers were identified as valued sources of health information. Most participants noted a paucity of water-treatment products. Sanitation, specifically the construction of latrines, was the most commonly identified need. Lack of funds was the primary reason given for not constructing a latrine. The construction and maintenance of potable water and sanitation services is needed to ensure a sustainable change. PMID:26562658

Interaction between nitric oxide and superoxide in the macula densa in aldosterone-induced alterations of tubuloglomerular feedback

PubMed Central

Zhang, Qian; Lin, Lin; Lu, Yan; Liu, Haifeng; Duan, Yanhua; Zhu, Xiaolong; Zou, Chengwei; Manning, R. Davis

2013-01-01

Tubuloglomerular feedback (TGF)-mediated constriction of the afferent arteriole is modulated by a balance between release of superoxide (O2−) and nitric oxide (NO) in macula densa (MD) cells. Aldosterone activates mineralocorticoid receptors that are expressed in the MD and induces both NO and O2− generation. We hypothesize that aldosterone enhances O2− production in the MD mediated by protein kinase C (PKC), which buffers the effect of NO in control of TGF response. Studies were performed in microdissected and perfused MD and in a MD cell line, MMDD1 cells. Aldosterone significantly enhanced O2− generation both in perfused MD and in MMDD1 cells. When aldosterone (10−7 mol/l) was added in the tubular perfusate, TGF response was reduced from 2.4 ± 0.3 μm to 1.4 ± 0.2 μm in isolated perfused MD. In the presence of tempol, a O2− scavenger, TGF response was 1.5 ± 0.2 μm. In the presence of both tempol and aldosterone in the tubular perfusate, TGF response was further reduced to 0.4 ± 0.2 μm. To determine if PKC is involved in aldosterone-induced O2− production, we exposed the O2− cells to a nonselective PKC inhibitor chelerythrine chloride, a specific PKCα inhibitor Go6976, or a PKCα siRNA, and the aldosterone-induced increase in O2− production was blocked. These data indicate that aldosterone-stimulated O2− production in the MD buffers the effect of NO in control of TGF response, an effect that was mediated by PKCα. PMID:23220724

Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies.

PubMed

Iurescia, Sandra; Fioretti, Daniela; Rinaldi, Monica

2018-01-01

The innate immune system provides the first line of defense against pathogen infection though also influences pathways involved in cancer immunosurveillance. The innate immune system relies on a limited set of germ line-encoded sensors termed pattern recognition receptors (PRRs), signaling proteins and immune response factors. Cytosolic receptors mediate recognition of danger damage-associated molecular patterns (DAMPs) signals. Once activated, these sensors trigger multiple signaling cascades, converging on the production of type I interferons and proinflammatory cytokines. Recent studies revealed that PRRs respond to nucleic acids (NA) released by dying, damaged, cancer cells, as danger DAMPs signals, and presence of signaling proteins across cancer types suggests that these signaling mechanisms may be involved in cancer biology. DAMPs play important roles in shaping adaptive immune responses through the activation of innate immune cells and immunological response to danger DAMPs signals is crucial for the host response to cancer and tumor rejection. Furthermore, PRRs mediate the response to NA in several vaccination strategies, including DNA immunization. As route of double-strand DNA intracellular entry, DNA immunization leads to expression of key components of cytosolic NA-sensing pathways. The involvement of NA-sensing mechanisms in the antitumor response makes these pathways attractive drug targets. Natural and synthetic agonists of NA-sensing pathways can trigger cell death in malignant cells, recruit immune cells, such as DCs, CD8 + T cells, and NK cells, into the tumor microenvironment and are being explored as promising adjuvants in cancer immunotherapies. In this minireview, we discuss how cGAS-STING and RIG-I-MAVS pathways have been targeted for cancer treatment in preclinical translational researches. In addition, we present a targeted selection of recent clinical trials employing agonists of cytosolic NA-sensing pathways showing how these pathways are currently being targeted for clinical application in oncology.

Respiratory syncytial virus induced type I IFN production by pDC is regulated by RSV-infected airway epithelial cells, RSV-exposed monocytes and virus specific antibodies.

PubMed

Schijf, Marcel A; Lukens, Michael V; Kruijsen, Debby; van Uden, Nathalie O P; Garssen, Johan; Coenjaerts, Frank E J; Van't Land, Belinda; van Bleek, Grada M

2013-01-01

Innate immune responses elicited upon virus exposure are crucial for the effective eradication of viruses, the onset of adaptive immune responses and for establishing proper immune memory. Respiratory syncytial virus (RSV) is responsible for a high disease burden in neonates and immune compromised individuals, causing severe lower respiratory tract infections. During primary infections exuberant innate immune responses may contribute to disease severity. Furthermore, immune memory is often insufficient to protect during RSV re-exposure, which results in frequent symptomatic reinfections. Therefore, identifying the cell types and pattern recognition receptors (PRRs) involved in RSV-specific innate immune responses is necessary to understand incomplete immunity against RSV. We investigated the innate cellular response triggered upon infection of epithelial cells and peripheral blood mononuclear cells. We show that CD14(+) myeloid cells and epithelial cells are the major source of IL-8 and inflammatory cytokines, IL-6 and TNF-α, when exposed to live RSV Three routes of RSV-induced IFN-α production can be distinguished that depend on the cross-talk of different cell types and the presence or absence of virus specific antibodies, whereby pDC are the ultimate source of IFN-α. RSV-specific antibodies facilitate direct TLR7 access into endosomal compartments, while in the absence of antibodies, infection of monocytes or epithelial cells is necessary to provide an early source of type I interferons, required to engage the IFN-α,β receptor (IFNAR)-mediated pathway of IFN-α production by pDC. However, at high pDC density infection with RSV causes IFN-α production without the need for a second party cell. Our study shows that cellular context and immune status are factors affecting innate immune responses to RSV. These issues should therefore be addressed during the process of vaccine development and other interventions for RSV disease.

Respiratory Syncytial Virus Induced Type I IFN Production by pDC Is Regulated by RSV-Infected Airway Epithelial Cells, RSV-Exposed Monocytes and Virus Specific Antibodies

PubMed Central

Schijf, Marcel A.; Lukens, Michael V.; Kruijsen, Debby; van Uden, Nathalie O. P.; Garssen, Johan; Coenjaerts, Frank E. J.; van’t Land, Belinda; van Bleek, Grada M.

2013-01-01

Innate immune responses elicited upon virus exposure are crucial for the effective eradication of viruses, the onset of adaptive immune responses and for establishing proper immune memory. Respiratory syncytial virus (RSV) is responsible for a high disease burden in neonates and immune compromised individuals, causing severe lower respiratory tract infections. During primary infections exuberant innate immune responses may contribute to disease severity. Furthermore, immune memory is often insufficient to protect during RSV re-exposure, which results in frequent symptomatic reinfections. Therefore, identifying the cell types and pattern recognition receptors (PRRs) involved in RSV-specific innate immune responses is necessary to understand incomplete immunity against RSV. We investigated the innate cellular response triggered upon infection of epithelial cells and peripheral blood mononuclear cells. We show that CD14+ myeloid cells and epithelial cells are the major source of IL-8 and inflammatory cytokines, IL-6 and TNF-α, when exposed to live RSV Three routes of RSV-induced IFN-α production can be distinguished that depend on the cross-talk of different cell types and the presence or absence of virus specific antibodies, whereby pDC are the ultimate source of IFN-α. RSV-specific antibodies facilitate direct TLR7 access into endosomal compartments, while in the absence of antibodies, infection of monocytes or epithelial cells is necessary to provide an early source of type I interferons, required to engage the IFN-α,β receptor (IFNAR)-mediated pathway of IFN-α production by pDC. However, at high pDC density infection with RSV causes IFN-α production without the need for a second party cell. Our study shows that cellular context and immune status are factors affecting innate immune responses to RSV. These issues should therefore be addressed during the process of vaccine development and other interventions for RSV disease. PMID:24303065

Memory T cell proliferative responses and IFN-γ productivity sustain long-lasting efficacy of a Cap-based PCV2 vaccine upon PCV2 natural infection and associated disease

PubMed Central

2014-01-01

Porcine circovirus type 2 (PCV2) vaccination represents an important measure to cope with PCV2 infection; however, data regarding the modulation of the immune cell compartment are still limited, especially under field conditions. This study is aimed at investigating the features of the cellular immune response in conventional piglets induced by vaccination using a capsid (Cap) protein-based PCV2 vaccine compared to unvaccinated animals when exposed to PCV2 natural infection. Immune reactivity was evaluated by quantifying peripheral cell subsets involved in the anti-viral response and characterizing the interferon-gamma (IFN-γ) secreting cell (SC) responsiveness both in vivo and upon in vitro whole PCV2 recall. The vaccination triggered an early and intense IFN-γ secreting cell response and induced the activation of peripheral lymphocytes. The early increase of IFN-γ SC frequencies resulted in a remarkable and transient tendency to increased IFN-γ productivity in vaccinated pigs. In vaccinated animals, soon before the onset of infection occurred 15-16 weeks post-vaccination, the recalled PCV2-specific immune response was characterized by moderate PCV2-specific IFN-γ secreting cell frequencies and augmented productivity together with reactive CD4+CD8+ memory T cells. Conversely, upon infection, unvaccinated animals showed very high frequencies of IFN-γ secreting cells and a tendency to lower productivity, which paralleled with effector CD4–CD8+ cytotoxic cell responsiveness. The study shows that PCV2 vaccination induces a long-lasting immunity sustained by memory T cells and IFN-γ secreting cells that potentially played a role in preventing the onset of infection; the extent and duration of this reactivity can be an important feature for evaluating the protective immunity induced by vaccination. PMID:24735253

Sugar inhibits the production of the toxins that trigger clostridial gas gangrene.

PubMed

Méndez, M B; Goñi, A; Ramirez, W; Grau, R R

2012-01-01

Histotoxic strains of Clostridium perfringens cause human gas gangrene, a devastating infection during which potent tissue-degrading toxins are produced and secreted. Although this pathogen only grows in anaerobic-nutrient-rich habitats such as deep wounds, very little is known regarding how nutritional signals influence gas gangrene-related toxin production. We hypothesize that sugars, which have been used throughout history to prevent wound infection, may represent a nutritional signal against gas gangrene development. Here we demonstrate, for the first time, that sugars (sucrose, glucose) inhibited the production of the main protein toxins, PLC (alpha-toxin) and PFO (theta-toxin), responsible for the onset and progression of gas gangrene. Transcription analysis experiments using plc-gusA and pfoA-gusA reporter fusions as well as RT-PCR analysis of mRNA transcripts confirmed that sugar represses plc and pfoA expression. In contrast an isogenic C. perfringens strain that is defective in CcpA, the master transcription factor involved in carbon catabolite response, was completely resistant to the sugar-mediated inhibition of PLC and PFO toxin production. Furthermore, the production of PLC and PFO toxins in the ccpA mutant strain was several-fold higher than the toxin production found in the wild type strain. Therefore, CcpA is the primary or unique regulatory protein responsible for the carbon catabolite (sugar) repression of toxin production of this pathogen. The present results are analyzed in the context of the role of CcpA for the development and aggressiveness of clostridial gas gangrene and the well-known, although poorly understood, anti-infective and wound healing effects of sugars and related substances. Copyright © 2011 Elsevier Ltd. All rights reserved.

Hierarchical signaling transduction of the immune and muscle cell crosstalk in muscle regeneration.

PubMed

Yang, Wenjun; Hu, Ping

2018-04-01

The muscle regeneration is a complicated bioprocess that involved in many cell types, including necrotic muscle cells, satellite cells, mesenchymal cells, pericytes, immune cells, and other cell types present at the injury site. Immune cells involved in both innate and adaptive immune responses regulate the progress of muscle regeneration. In this review, we discussed the roles of different immune cells in muscle regeneration. The immune cells regulate muscle regeneration through cytokine production, cell-cell contacts, and general immune environment regulation. We also describe the current known mechanism of how immune cells regulating muscle regeneration. Copyright © 2017. Published by Elsevier Inc.

Consumers responses to coupons in direct-to-consumer advertising of prescription drugs.

PubMed

Bhutada, Nilesh S; Cook, Christopher L; Perri, Matthew

2009-01-01

A study was conducted to understand the influence of coupons and consumers' level of involvement in direct-to-consumer advertising. Consumers exposed to prescription drug advertising with a coupon had significantly more favorable ad and brand-related attitudes, and intention to inquire about the drug to their doctor. However, there was no significant difference in perceived product risk between consumers exposed to the ad with a coupon and consumers exposed to the ad without a coupon. Highly involved consumers had significantly more favorable ad, brand, and coupon-related attitudes, drug inquiry intention, and perceptions about the risks associated with the drug.

Effect of IFN-γ, IL-12 and IL-10 cytokine production and mRNA expression in tuberculosis patients with diabetes mellitus and their household contacts.

PubMed

Meenakshi, Ponnana; Ramya, Sivangala; Lavanya, Joshi; Vijayalakshmi, Valluri; Sumanlatha, Gaddam

2016-05-01

The study was carried out to understand the influence of IFN-γ, IL-12 and IL-10 cytokine production and expression in tuberculosis patients with diabetes mellitus (TBDM) and their household contacts (HHC). The study involved a total of 300 subjects, 50 in each category of TBDM, TBDM HHC, pulmonary tuberculosis patients (PTB), PTB HHC, DM and healthy controls (HC). TBDM, PTB and their HHC, 25 each were followed at different intervals to determine their immune responses in Ag85A stimulated culture supernatants by Enzyme Linked Immunosorbent Assay (ELISA). mRNA expression by TRIZOL method in 5 cases of each category and follow-up studies were performed. IFN-γ and IL-12 cytokine production markedly decreased and that of IL-10 increased after Ag85A M.tb stimulation, however anti TB treatment reconstituted the response in TBDM and PTB patients. The household contacts revealed cytokine gene expression similar to that of patients and two of them developed the disease during follow-up. Cytokine responses of the patients retained after treatment highlighting the antigen importance, hence further studies with recombinant cytokines may help in coming up with a biomarker. Analogous immune responses of household contacts with the TBDM and PTB patients may assist in recognizing the high risk individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neural signatures of response planning occur midway through an incoming question in conversation

PubMed Central

Bögels, Sara; Magyari, Lilla; Levinson, Stephen C.

2015-01-01

A striking puzzle about language use in everyday conversation is that turn-taking latencies are usually very short, whereas planning language production takes much longer. This implies overlap between language comprehension and production processes, but the nature and extent of such overlap has never been studied directly. Combining an interactive quiz paradigm with EEG measurements in an innovative way, we show that production planning processes start as soon as possible, that is, within half a second after the answer to a question can be retrieved (up to several seconds before the end of the question). Localization of ERP data shows early activation even of brain areas related to late stages of production planning (e.g., syllabification). Finally, oscillation results suggest an attention switch from comprehension to production around the same time frame. This perspective from interactive language use throws new light on the performance characteristics that language competence involves. PMID:26242909

Expanding the B Cell Centric View of Systemic Lupus Erythematosus

PubMed Central

Morawski, Peter A.; Bolland, Silvia

2017-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a breakdown of self-tolerance in B cells and production of antibodies against nuclear self-antigens. Increasing evidence supports the notion that additional cellular contributors beyond B cells are important for lupus pathogenesis. In this Review, we consider recent advances regarding both pathogenic and regulatory roles of lymphocytes in SLE, beyond the production of IgG autoantibodies. We also discuss various inflammatory effector cell types involved in cytokine production, removal of self-antigens, and responses to autoreactive IgE antibodies. We aim to integrate these ideas to expand the current understanding of the cellular components that contribute to disease progression and ultimately help in the design of novel targeted therapeutics. PMID:28274696

Precultivation of Bacillus coagulans DSM2314 in the presence of furfural decreases inhibitory effects of lignocellulosic by-products during L(+)-lactic acid fermentation.

PubMed

van der Pol, Edwin; Springer, Jan; Vriesendorp, Bastienne; Weusthuis, Ruud; Eggink, Gerrit

2016-12-01

By-products resulting from thermo-chemical pretreatment of lignocellulose can inhibit fermentation of lignocellulosic sugars to lactic acid. Furfural is such a by-product, which is formed during acid pretreatment of lignocellulose. pH-controlled fermentations with 1 L starting volume, containing YP medium and a mixture of lignocellulosic by-products, were inoculated with precultures of Bacillus coagulans DSM2314 to which 1 g/L furfural was added. The addition of furfural to precultures resulted in an increase in L(+)-lactic acid productivity by a factor 2 to 1.39 g/L/h, an increase in lactic acid production from 54 to 71 g and an increase in conversion yields of sugar to lactic acid from 68 to 88 % W/W in subsequent fermentations. The improved performance was not caused by furfural consumption or conversion, indicating that the cells acquired a higher tolerance towards this by-product. The improvement coincided with a significant elongation of B. coagulans cells. Via RNA-Seq analysis, an upregulation of pathways involved in the synthesis of cell wall components such as bacillosamine, peptidoglycan and spermidine was observed in elongated cells. Furthermore, the gene SigB and genes promoted by SigB, such as NhaX and YsnF, were upregulated in the presence of furfural. These genes are involved in stress responses in bacilli.

Interleukin 6 Influences Germinal Center Development and Antibody Production via a Contribution of C3 Complement Component

PubMed Central

Kopf, Manfred; Herren, Suzanne; Wiles, Michael V.; Pepys, Mark B.; Kosco-Vilbois, Marie H.

1998-01-01

Mice rendered deficient for interleukin (IL) 6 by gene targeting were evaluated for their response to T cell–dependent antigens. Antigen-specific immunoglobulin (Ig)M levels were unaffected whereas all IgG isotypes showed varying degrees of alteration. Germinal center reactions occurred but remained physically smaller in comparison to those in the wild-type mice. This concurred with the observations that molecules involved in initial signaling events leading to germinal center formation were not altered (e.g., B7.2, CD40 and tumor necrosis factor R1). T cell priming was not impaired nor was a gross imbalance of T helper cell (Th) 1 versus Th2 cytokines observed. However, B7.1 molecules, absent from wild-type counterparts, were detected on germinal center B cells isolated from the deficient mice suggesting a modification of costimulatory signaling. A second alteration involved impaired de novo synthesis of C3 both in serum and germinal center cells from IL-6–deficient mice. Indeed, C3 provided an essential stimulatory signal for wild-type germinal center cells as both monoclonal antibodies that interrupted C3-CD21 interactions and sheep anti–mouse C3 antibodies caused a significant decrease in antigen-specific antibody production. In addition, germinal center cells isolated from C3–deficient mice produced a similar defect in isotype production. Low density cells with dendritic morphology were the local source of IL-6 and not the germinal center lymphocytes. Adding IL-6 in vitro to IL-6–deficient germinal center cells stimulated cell cycle progression and increased levels of antibody production. These findings reveal that the germinal center produces and uses molecules of the innate immune system, evolutionarily pirating them in order to optimally generate high affinity antibody responses. PMID:9815267

Effects of temperature on the production of hydrogen peroxide and volatile halocarbons by brackish-water algae.

PubMed

Abrahamsson, Katarina; Choo, Kyung Sil; Pedersén, Marianne; Johansson, Gustav; Snoeijs, Pauli

2003-10-01

Marine algae produce volatile halocarbons, which have an ozone-depleting potential. The formation of these compounds is thought to be related to oxidative stress, involving H2O2 and algal peroxidases. In our study we found strong correlations between the releases of H2O2 and brominated and some iodinated compounds to the seawater medium, but no such correlation was found for CHCl3, suggesting the involvement of other formation mechanisms as well. Little is known about the effects of environmental factors on the production of volatile halocarbons by algae and in the present study we focused on the influence of temperature. Algae were sampled in an area of the brackish Baltic Sea that receives thermal discharge, allowing us to collect specimens of the same species that were adapted to different field temperature regimes. We exposed six algal species (the diatom Pleurosira laevis, the brown alga Fucus vesiculosus and four filamentous green algae, Cladophora glomerata, Enteromorpha ahlneriana, E. flexuosa and E. intestinalis) to temperature changes of 0-11 degrees C under high irradiation to invoke oxidative stress. The production rates, as well as the quantitative composition of 16 volatile halocarbons, were strongly species-dependent and different types of responses to temperature were recorded. However, no response patterns to temperature change were found that were consistent for all species or for all halocarbons. We conclude that the production of certain halocarbons may increase with temperature in certain algal species, but that the amount and composition of the volatile halocarbons released by algal communities are probably more affected by temperature-associated species shifts. These results may have implications for climatic change scenarios.

Differentiation of Effector CD4 T Cell Populations*

PubMed Central

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

2012-01-01

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

Transcriptome analysis identifies genes involved in ethanol response of Saccharomyces cerevisiae in Agave tequilana juice.

PubMed

Ramirez-Córdova, Jesús; Drnevich, Jenny; Madrigal-Pulido, Jaime Alberto; Arrizon, Javier; Allen, Kirk; Martínez-Velázquez, Moisés; Alvarez-Maya, Ikuri

2012-08-01

During ethanol fermentation, yeast cells are exposed to stress due to the accumulation of ethanol, cell growth is altered and the output of the target product is reduced. For Agave beverages, like tequila, no reports have been published on the global gene expression under ethanol stress. In this work, we used microarray analysis to identify Saccharomyces cerevisiae genes involved in the ethanol response. Gene expression of a tequila yeast strain of S. cerevisiae (AR5) was explored by comparing global gene expression with that of laboratory strain S288C, both after ethanol exposure. Additionally, we used two different culture conditions, cells grown in Agave tequilana juice as a natural fermentation media or grown in yeast-extract peptone dextrose as artificial media. Of the 6368 S. cerevisiae genes in the microarray, 657 genes were identified that had different expression responses to ethanol stress due to strain and/or media. A cluster of 28 genes was found over-expressed specifically in the AR5 tequila strain that could be involved in the adaptation to tequila yeast fermentation, 14 of which are unknown such as yor343c, ylr162w, ygr182c, ymr265c, yer053c-a or ydr415c. These could be the most suitable genes for transforming tequila yeast to increase ethanol tolerance in the tequila fermentation process. Other genes involved in response to stress (RFC4, TSA1, MLH1, PAU3, RAD53) or transport (CYB2, TIP20, QCR9) were expressed in the same cluster. Unknown genes could be good candidates for the development of recombinant yeasts with ethanol tolerance for use in industrial tequila fermentation.

Combining gene expression and genetic analyses to identify candidate genes involved in cold responses in pea.

PubMed

Legrand, Sylvain; Marque, Gilles; Blassiau, Christelle; Bluteau, Aurélie; Canoy, Anne-Sophie; Fontaine, Véronique; Jaminon, Odile; Bahrman, Nasser; Mautord, Julie; Morin, Julie; Petit, Aurélie; Baranger, Alain; Rivière, Nathalie; Wilmer, Jeroen; Delbreil, Bruno; Lejeune-Hénaut, Isabelle

2013-09-01

Cold stress affects plant growth and development. In order to better understand the responses to cold (chilling or freezing tolerance), we used two contrasted pea lines. Following a chilling period, the Champagne line becomes tolerant to frost whereas the Terese line remains sensitive. Four suppression subtractive hybridisation libraries were obtained using mRNAs isolated from pea genotypes Champagne and Terese. Using quantitative polymerase chain reaction (qPCR) performed on 159 genes, 43 and 54 genes were identified as differentially expressed at the initial time point and during the time course study, respectively. Molecular markers were developed from the differentially expressed genes and were genotyped on a population of 164 RILs derived from a cross between Champagne and Terese. We identified 5 candidate genes colocalizing with 3 different frost damage quantitative trait loci (QTL) intervals and a protein quantity locus (PQL) rich region previously reported. This investigation revealed the role of constitutive differences between both genotypes in the cold responses, in particular with genes related to glycine degradation pathway that could confer to Champagne a better frost tolerance. We showed that freezing tolerance involves a decrease of expression of genes related to photosynthesis and the expression of a gene involved in the production of cysteine and methionine that could act as cryoprotectant molecules. Although it remains to be confirmed, this study could also reveal the involvement of the jasmonate pathway in the cold responses, since we observed that two genes related to this pathway were mapped in a frost damage QTL interval and in a PQL rich region interval, respectively. Copyright © 2013 Elsevier GmbH. All rights reserved.

Carbon dioxide sequestration by chemolithotrophic oleaginous bacteria for production and optimization of polyhydroxyalkanoate.

PubMed

Kumar, Manish; Gupta, Asmita; Thakur, Indu Shekhar

2016-08-01

The present work involved screening of a previously reported carbon concentrating oleaginous bacterial strain Serratia sp. ISTD04 for production of PHA and optimization of process parameters for enhanced PHA and biomass generation. The selected bacterial strain was screened for PHA production based on Nile red staining followed by visualization under fluorescence microscope. Spectrofluorometric measurement of Nile red fluorescence of the bacterial culture was also done. Confirmatory analysis of PHA accumulation by GC-MS revealed the presence of 3-hydroxyvalerate. Detection of characteristic peaks in the FT-IR spectrum further confirmed the production of PHA by the bacterium. Response Surface Methodology was used for optimization of pH and carbon sources' concentrations for higher PHA production. There was almost a 2 fold increase in the production of PHA following optimization as compared to un-optimized condition. The study thus establishes the production of PHA by Serratia sp. ISTD04. Copyright © 2016 Elsevier Ltd. All rights reserved.

Constant light suppresses production of Met-enkephalin-containing peptides in cultured splenic macrophages and impairs primary immune response in rats.

PubMed

Valdés-Tovar, Marcela; Escobar, Carolina; Solís-Chagoyán, Héctor; Asai, Miguel; Benítez-King, Gloria

2015-03-01

The light-dark cycle is an environmental factor that influences immune physiology, and so, variations of the photoperiod length result in altered immune responsivity. Macrophage physiology comprises a spectrum of functions that goes from host defense to immune down-regulation, in addition to their homeostatic activities. Macrophages also play a key role in the transition from innate to adaptive immune responses. Met-enkephalin (MEnk) has been recognized as a modulator of macrophage physiology acting in an autocrine or paracrine fashion to influence macrophage activation, phenotype polarization and production of cytokines that would enhance lymphocyte activation at early stages of an immune response. Previously it was shown that splenic MEnk tissue content is reduced in rats exposed to constant light. In this work, we explored whether production of Met-enkephalin-containing peptides (MECPs) in cultured splenic macrophages is affected by exposure of rats to a constant light regime. In addition, we explored whether primary immune response was impaired under this condition. We found that in rats, 15 days in constant light was sufficient to disrupt their general activity rhythm. Splenic MEnk content oscillations and levels were also blunted throughout a 24-h period in animals subjected to constant light. In agreement, de novo synthesis of MECPs evaluated through incorporation of (35)S-methionine was reduced in splenic macrophages from rats exposed to constant light. Moreover, MECPs immunocytochemistry showed a decrease in the intracellular content and lack of granule-like deposits in this condition. Furthermore, we found that primary T-dependent antibody response was compromised in rats exposed to constant light. In those animals, pharmacologic treatment with MEnk increased IFN-γ-secreting cells. Also, IL-2 secretion from antigen-stimulated splenocytes was reduced after incubation with naloxone, suggesting that immune-derived opioid peptides and stimulation of opioid receptors are involved in this process. Thus, the immune impairment observed from early stages of the response in constant light-subjected rats, could be associated with reduced production of macrophage-derived enkephalins, leading to a sub-optimal interaction between macrophages and lymphocytes in the spleen and the subsequent deficiency in antibody production.

Ectopic Expression of JcWRKY Confers Enhanced Resistance in Transgenic Tobacco Against Macrophomina phaseolina.

PubMed

Agarwal, Parinita; Patel, Khantika; Agarwal, Pradeep K

2018-04-01

Plants possess an innate immune system comprising of a complex network of closely regulated defense responses involving differential gene expression mediated by transcription factors (TFs). The WRKYs comprise of an important plant-specific TF family, which is involved in regulation of biotic and abiotic defenses. The overexpression of JcWRKY resulted in improved resistance in transgenic tobacco against Macrophomina phaseolina. The production of reactive oxygen species (ROS) and its detoxification through antioxidative system in the transgenics facilitates defense against Macrophomina. The enhanced catalase activity on Macrophomina infection limits the spread of infection. The transcript expression of antioxidative enzymes gene (CAT and SOD) and salicylic acid (SA) biosynthetic gene ICS1 showed upregulation during Macrophomina infection and combinatorial stress. The enhanced transcript of pathogenesis-related genes PR-1 indicates the accumulation of SA during different stresses. The PR-2 and PR-5 highlight the activation of defense responses comprising of activation of hydrolytic cleavage of glucanases and thaumatin-like proteins causing disruption of fungal cells. The ROS homeostasis in coordination with signaling molecules regulate the defense responses and inhibit fungal growth.

Gel-based and gel-free proteomic analysis of Nicotiana tabacum trichomes identifies proteins involved in secondary metabolism and in the (a)biotic stress response.

PubMed

Van Cutsem, Emmanuel; Simonart, Géraldine; Degand, Hervé; Faber, Anne-Marie; Morsomme, Pierre; Boutry, Marc

2011-02-01

Nicotiana tabacum leaves are covered by trichomes involved in the secretion of large amounts of secondary metabolites, some of which play a major role in plant defense. However, little is known about the metabolic pathways that operate in these structures. We undertook a proteomic analysis of N. tabacum trichomes in order to identify their protein complement. Efficient trichome isolation was obtained by abrading frozen leaves. After homogenization, soluble proteins and a microsomal fraction were prepared by centrifugation. Gel-based and gel-free proteomic analyses were then performed. 2-DE analysis of soluble proteins led to the identification of 1373 protein spots, which were digested and analyzed by MS/MS, leading to 680 unique identifications. Both soluble proteins and microsomal fraction were analyzed by LC MALDI-MS/MS after trypsin digestion, leading to 858 identifications, many of which had not been identified after 2-DE, indicating that the two methods complement each other. Many enzymes putatively involved in secondary metabolism were identified, including enzymes involved in the synthesis of terpenoid precursors and in acyl sugar production. Several transporters were also identified, some of which might be involved in secondary metabolite transport. Various (a)biotic stress response proteins were also detected, supporting the role of trichomes in plant defense. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of TNF-α production inhibitors on the production of pro-inflammatory cytokines by peripheral blood mononuclear cells from HTLV-1-infected individuals.

PubMed

Luna, T; Santos, S B; Nascimento, M; Porto, M A F; Muniz, A L; Carvalho, E M; Jesus, A R

2011-11-01

Human T lymphotropic virus type 1 (HTLV-1) is the causal agent of myelopathy/tropical spastic paraparesis (HAM/TSP), a disease mediated by the immune response. HTLV-1 induces a spontaneous proliferation and production of pro-inflammatory cytokines by T cells, and increasing interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) levels are potentially involved in tissue damage in diseases related to HTLV-1. This exaggerated immune response is also due to an inability of the natural regulatory mechanisms to down-modulate the immune response in this group of patients. TNF-α inhibitors reduce inflammation and have been shown to improve chronic inflammatory diseases in clinical trials. The aim of this study was to evaluate the ability of pentoxifylline, forskolin, rolipram, and thalidomide to decrease in vitro production of TNF-α and IFN-γ in cells of HTLV-1-infected subjects. Participants of the study included 19 patients with HAM/TSP (mean age, 53 ± 11; male:female ratio, 1:1) and 18 HTLV-1 carriers (mean age, 47 ± 11; male:female ratio, 1:2.6). Cytokines were determined by ELISA in supernatants of mononuclear cell cultures. Pentoxifylline inhibited TNF-α and IFN-γ synthesis with the minimum dose used (50 µM). The results with forskolin were similar to those observed with pentoxifylline. The doses of rolipram used were 0.01-1 µM and the best inhibition of TNF-α production was achieved with 1 µM and for IFN-γ production it was 0.01 µM. The minimum dose of thalidomide used (1 µM) inhibited TNF-α production but thalidomide did not inhibit IFN-γ production even when the maximum dose (50 µM) was used. All drugs had an in vitro inhibitory effect on TNF-α production and, with the exception of thalidomide, all of them also decreased IFN-γ production.

Study of obligations defined in agreements between parties involved in clinical trials of medicinal products in Bulgaria.

PubMed

N Getov, Ilko; Gocheva-Hristova, Tanya; Lebanova, Hristina V; Grigorov, Evgeni E

2012-08-01

To analyse and assess the legislative and contractual obligations of the parties involved in the conduct of clinical trials, with identification of the needs for comprehensive contractual regulation of their rights and responsibilities. This survey has been carried out by means of review, analysis of comprehensiveness, comparative legislative analysis and assessment of compliance with the legislation of sample of investigator and site agreements governing the process of conducting clinical trials. The survey comprises analyses of contractual relations between the sponsor of the study and the investigator, and between the sponsor of the study and the trial site, respectively, relevant to clinical trials which are actually conducted in Bulgaria at the time of and following the survey. Comparative method based on pre-defined structured indices was employed to outline the major variances in the volume of responsibilities and obligations of the said parties to the clinical trial, as regulated by the investigator and site agreements. The analysis of comprehensiveness showed evident omissions in the regulation of relations and interactions between the parties to the agreements. The detailed contractual regulation providing for the statutory obligations and responsibilities of the parties involved in the conduct of clinical trials is a good guarantee for proper understanding of the obligations of each party and for compliance with their relevant responsibilities in view of protecting the rights of the participants in the clinical trials - patients or healthy volunteers.

Recent Advances in Utilizing Transcription Factors to Improve Plant Abiotic Stress Tolerance by Transgenic Technology

PubMed Central

Wang, Hongyan; Wang, Honglei; Shao, Hongbo; Tang, Xiaoli

2016-01-01

Agricultural production and quality are adversely affected by various abiotic stresses worldwide and this will be exacerbated by the deterioration of global climate. To feed a growing world population, it is very urgent to breed stress-tolerant crops with higher yields and improved qualities against multiple environmental stresses. Since conventional breeding approaches had marginal success due to the complexity of stress tolerance traits, the transgenic approach is now being popularly used to breed stress-tolerant crops. So identifying and characterizing the critical genes involved in plant stress responses is an essential prerequisite for engineering stress-tolerant crops. Far beyond the manipulation of single functional gene, engineering certain regulatory genes has emerged as an effective strategy now for controlling the expression of many stress-responsive genes. Transcription factors (TFs) are good candidates for genetic engineering to breed stress-tolerant crop because of their role as master regulators of many stress-responsive genes. Many TFs belonging to families AP2/EREBP, MYB, WRKY, NAC, bZIP have been found to be involved in various abiotic stresses and some TF genes have also been engineered to improve stress tolerance in model and crop plants. In this review, we take five large families of TFs as examples and review the recent progress of TFs involved in plant abiotic stress responses and their potential utilization to improve multiple stress tolerance of crops in the field conditions. PMID:26904044

Changes in cytokine production associated with acquired immunity to Plasmodium falciparum malaria

PubMed Central

Rhee, M S M; Akanmori, B D; Waterfall, M; Riley, E M

2001-01-01

Individuals living in malaria-endemic areas eventually develop clinical immunity to Plasmodium falciparum. That is, they are able to limit blood parasite densities to extremely low levels and fail to show symptoms of infection. As the clinical symptoms of malaria infection are mediated in part by pro-inflammatory cytokines it is not clear whether the acquisition of clinical immunity is due simply to the development of antiparasitic mechanisms or whether the ability to regulate inflammatory cytokine production is also involved. We hypothesize that there is a correlation between risk of developing clinical malaria and the tendency to produce high levels of proinflammatory cytokines in response to malaria infection. In order to test this hypothesis, we have compared the ability of peripheral blood mononuclear cells from malaria-naive and malaria-exposed adult donors to proliferate and to secrete IFN-γ in response to P. falciparum schizont extract (PfSE). In order to determine how PfSE-induced IFN-γ production is regulated, we have also measured production of IL-12p40 and IL-10 from PfSE-stimulated PBMC and investigated the role of neutralizing antibody to IL-12 in modulating IFN-γ production. We find that cells from naive donors produce moderate amounts of IFN-γ in response to PfSE and that IFN-γ production is strongly IL-12 dependent. Cells from malaria-exposed donors living in an area of low malaria endemicity produce much higher levels of IFN-γ and this response is also at least partially IL-12 dependent. In complete contrast, cells from donors living in an area of very high endemicity produce minimal amounts of IFN-γ. No significant differences were detected between the groups in IL-10 production, suggesting that this cytokine does not play a major role in regulating malaria-induced IFN-γ production. The data from this study thus strongly support the hypothesis that down-regulation of inflammatory cytokine production may be a component of acquired clinical immunity to malaria but the mechanism by which this is achieved remains to be elucidated. PMID:11737069

A Quick and Handy Guide to Educational Mentoring. A Product of a 310 Special Demonstration Training Project 1982-83, "Training Mentors as Educational Counselors of Adult Learners."

ERIC Educational Resources Information Center

Singer, Elizabeth

Developed in two training sessions involving key personnel from business, industry, and community agencies who counsel employees or clients about career changes, this handbook is intended to help persons who are responsible for guiding adults through educational or career changes. The guide is organized into 11 sections. Topics covered by these…

[Iron from soil to plant products].

PubMed

Briat, Jean-François

2005-11-01

As an essential mineral, iron plays an important role in fundamental biological processes such as photosynthesis, respiration, nitrogen fixation and assimilation, and DNA synthesis. Iron is also a co-factor of many enzymes involved in the synthesis of plant hormones. The latter are involved in many pathways controling plant development or adaptative responses to environmental conditions. Iron reactivity with oxygen leads to its insolubility (responsible for deficiency) and potential toxicity, and complicates iron use by aerobic organisms. If plants lacked an active root system with which to acquire iron from the soil, most would experience iron deficiency and show physiological changes. In contrast, an excess of soluble iron, which can occur in flooded acidic soils, can lead to ferrous iron toxicity due to iron reactivity with reduced forms of oxygen and subsequent free radical production. An optimal iron concentration is thus required for a plant to grow and develop normally. This concentration depends on multiple regulatory mechanisms controlling iron uptake from soil by the roots, as well as iron transport and distribution to the various plant organs. Optimized seed iron content is a major biotechnological challenge identified by the World Health Organization, and it is therefore crucial to understand the underlying mechanisms. Iron delivery to seeds is tightly controlled, and depends on the nature of iron speciation in specific chelates, and their transport.

The influence of serial repitching of Saccharomyces pastorianus on its karyotype and protein profile during the fermentation of gluten-free buckwheat and quinoa wort.

PubMed

Deželak, Matjaž; Gebremariam, Mekonnen M; Cadež, Neža; Zupan, Jure; Raspor, Peter; Zarnkow, Martin; Becker, Thomas; Košir, Iztok Jože

2014-08-18

Gluten-free beer-like beverages from malted buckwheat and quinoa are somehow close to their commercial production, but rather high expenses are expected due to the relatively high price of grain, some technological adaptations of process and the need for external enzyme supplementation during mashing. One of the common and efficient cost reduction measures in the industrial scale is serial repitching of the yeast biomass, which has not been studied for the buckwheat and quinoa wort fermentation before. In that manner we have monitored possible changes in yeast's proteins and chromosomal DNA during eleven serial repitchings of the yeast Saccharomyces pastorianus strain TUM 34/70 for fermentation of the barley, buckwheat and quinoa wort. Karyotypes showed changes in regard to the raw materials used and many responsible candidate proteins are suggested which could cause these differences. Different relative expressions of some protein bands were also linked to the proteins involved in yeast stress response and proteins involved in fermentation performance. Results suggest that serial repitching of the strain TUM 34/70 seems suitable for the production of gluten-free beer-like beverages from buckwheat and quinoa. Copyright © 2014 Elsevier B.V. All rights reserved.

Investigating the role of state permitting and agriculture agencies in addressing public health concerns related to industrial food animal production.

PubMed

Fry, Jillian P; Laestadius, Linnea I; Grechis, Clare; Nachman, Keeve E; Neff, Roni A

2014-01-01

Industrial food animal production (IFAP) operations adversely impact environmental public health through air, water, and soil contamination. We sought to determine how state permitting and agriculture agencies respond to these public health concerns. We conducted semi-structured qualitative interviews with staff at 12 state agencies in seven states, which were chosen based on high numbers or rapid increase of IFAP operations. The interviews served to gather information regarding agency involvement in regulating IFAP operations, the frequency and type of contacts received about public health concerns, how the agency responds to such contacts, and barriers to additional involvement. Permitting and agriculture agencies' responses to health-based IFAP concerns are constrained by significant barriers including narrow regulations, a lack of public health expertise within the agencies, and limited resources. State agencies with jurisdiction over IFAP operations are unable to adequately address relevant public health concerns due to multiple factors. Combining these results with previously published findings on barriers facing local and state health departments in the same states reveals significant gaps between these agencies regarding public health and IFAP. There is a clear need for regulations to protect public health and for public health professionals to provide complementary expertise to agencies responsible for regulating IFAP operations.

The Extent of Consumer Product Involvement in Paediatric Injuries

PubMed Central

Catchpoole, Jesani; Walker, Sue; Vallmuur, Kirsten

2016-01-01

A challenge in utilising health sector injury data for Product Safety purposes is that clinically coded data have limited ability to inform regulators about product involvement in injury events, given data entry is bound by a predefined set of codes. Text narratives collected in emergency departments can potentially address this limitation by providing relevant product information with additional accompanying context. This study aims to identify and quantify consumer product involvement in paediatric injuries recorded in emergency department-based injury surveillance data. A total of 7743 paediatric injuries were randomly selected from Queensland Injury Surveillance Unit database and associated text narratives were manually reviewed to determine product involvement in the injury event. A Product Involvement Factor classification system was used to categorise these injury cases. Overall, 44% of all reviewed cases were associated with consumer products, with proximity factor (25%) being identified as the most common involvement of a product in an injury event. Only 6% were established as being directly due to the product. The study highlights the importance of utilising injury data to inform product safety initiatives where text narratives can be used to identify the type and involvement of products in injury cases. PMID:27399744

The Extent of Consumer Product Involvement in Paediatric Injuries.

PubMed

Catchpoole, Jesani; Walker, Sue; Vallmuur, Kirsten

2016-07-07

A challenge in utilising health sector injury data for Product Safety purposes is that clinically coded data have limited ability to inform regulators about product involvement in injury events, given data entry is bound by a predefined set of codes. Text narratives collected in emergency departments can potentially address this limitation by providing relevant product information with additional accompanying context. This study aims to identify and quantify consumer product involvement in paediatric injuries recorded in emergency department-based injury surveillance data. A total of 7743 paediatric injuries were randomly selected from Queensland Injury Surveillance Unit database and associated text narratives were manually reviewed to determine product involvement in the injury event. A Product Involvement Factor classification system was used to categorise these injury cases. Overall, 44% of all reviewed cases were associated with consumer products, with proximity factor (25%) being identified as the most common involvement of a product in an injury event. Only 6% were established as being directly due to the product. The study highlights the importance of utilising injury data to inform product safety initiatives where text narratives can be used to identify the type and involvement of products in injury cases.

Coral-zooxanthellae meta-transcriptomics reveals integrated response to pollutant stress.

PubMed

Gust, Kurt A; Najar, Fares Z; Habib, Tanwir; Lotufo, Guilherme R; Piggot, Alan M; Fouke, Bruce W; Laird, Jennifer G; Wilbanks, Mitchell S; Rawat, Arun; Indest, Karl J; Roe, Bruce A; Perkins, Edward J

2014-07-12

Corals represent symbiotic meta-organisms that require harmonization among the coral animal, photosynthetic zooxanthellae and associated microbes to survive environmental stresses. We investigated integrated-responses among coral and zooxanthellae in the scleractinian coral Acropora formosa in response to an emerging marine pollutant, the munitions constituent, 1,3,5-trinitro-1,3,5 triazine (RDX; 5 day exposures to 0 (control), 0.5, 0.9, 1.8, 3.7, and 7.2 mg/L, measured in seawater). RDX accumulated readily in coral soft tissues with bioconcentration factors ranging from 1.1 to 1.5. Next-generation sequencing of a normalized meta-transcriptomic library developed for the eukaryotic components of the A. formosa coral holobiont was leveraged to conduct microarray-based global transcript expression analysis of integrated coral/zooxanthellae responses to the RDX exposure. Total differentially expressed transcripts (DET) increased with increasing RDX exposure concentrations as did the proportion of zooxanthellae DET relative to the coral animal. Transcriptional responses in the coral demonstrated higher sensitivity to RDX compared to zooxanthellae where increased expression of gene transcripts coding xenobiotic detoxification mechanisms (i.e. cytochrome P450 and UDP glucuronosyltransferase 2 family) were initiated at the lowest exposure concentration. Increased expression of these detoxification mechanisms was sustained at higher RDX concentrations as well as production of a physical barrier to exposure through a 40% increase in mucocyte density at the maximum RDX exposure. At and above the 1.8 mg/L exposure concentration, DET coding for genes involved in central energy metabolism, including photosynthesis, glycolysis and electron-transport functions, were decreased in zooxanthellae although preliminary data indicated that zooxanthellae densities were not affected. In contrast, significantly increased transcript expression for genes involved in cellular energy production including glycolysis and electron-transport pathways was observed in the coral animal. Transcriptional network analysis for central energy metabolism demonstrated highly correlated responses to RDX among the coral animal and zooxanthellae indicative of potential compensatory responses to lost photosynthetic potential within the holobiont. These observations underscore the potential for complex integrated responses to RDX exposure among species comprising the coral holobiont and highlight the need to understand holobiont-species interactions to accurately assess pollutant impacts.

Postmarketing surveillance: perspectives of a journal editor.

PubMed

Gelenberg, A J

1993-01-01

In the absence of a systematic monitoring program for drugs newly approved by the Food and Drug Administration (FDA), reports in clinical journals provide a legitimate forum for disseminating information about unexpected pharmacologic events. A journal editor bears the responsibility for publishing educated clinical observations that meet standards of scientific rigor while not giving premature credibility to chance and dubious reports of side effects of new drugs. Often this responsibility involves overcoming the fear of bad publicity and withstanding pressures from pharmaceutical companies to print only positive information about new products. Published preliminary observations may contribute to the problem of product liability, but they also generate testable hypotheses and healthy debate. If hypotheses later prove to be incorrect, they can be refuted by systematic studies and clarified in reviews and editorials. Our goal of effective education will be reached not by self-censorship but by scientific openness.

Augmentation of chemokine production by severe acute respiratory syndrome coronavirus 3a/X1 and 7a/X4 proteins through NF-kappaB activation.

PubMed

Kanzawa, Noriyuki; Nishigaki, Kazuo; Hayashi, Takaya; Ishii, Yuichi; Furukawa, Souichi; Niiro, Ayako; Yasui, Fumihiko; Kohara, Michinori; Morita, Kouichi; Matsushima, Kouji; Le, Mai Quynh; Masuda, Takao; Kannagi, Mari

2006-12-22

Severe acute respiratory syndrome (SARS) is characterized by rapidly progressing respiratory failure resembling acute/adult respiratory distress syndrome (ARDS) associated with uncontrolled inflammatory responses. Here, we demonstrated that, among five accessory proteins of SARS coronavirus (SARS-CoV) tested, 3a/X1 and 7a/X4 were capable of activating nuclear factor kappa B (NF-kappaB) and c-Jun N-terminal kinase (JNK), and significantly enhanced interleukin 8 (IL-8) promoter activity. Furthermore, 3a/X1 and 7a/X4 expression in A549 cells enhanced production of inflammatory chemokines that were known to be up-regulated in SARS-CoV infection. Our results suggest potential involvement of 3a/X1 and 7a/X4 proteins in the pathological inflammatory responses in SARS.

The bacterial preparation OK432 induces IL-12p70 secretion in human dendritic cells in a TLR3 dependent manner.

PubMed

Hovden, Arnt-Ove; Karlsen, Marie; Jonsson, Roland; Appel, Silke

2012-01-01

Dendritic cells (DC) used in therapeutic cancer immunotherapy have to be able to stimulate T cells resulting in an immune response that can efficiently target the cancer cells. One of the critical hurdles has been the lack of IL-12p70 production when maturating the DC, which is rectified by using the bacterial preparation OK432 (trade name Picibanil) to mature the cells. In order to identify the mechanism behind OK432 stimulation of DC, we investigated the contribution of different TLR to examine their involvement in IL-12p70 production. By combining different inhibitors of TLR signaling, we demonstrate here that TLR3 is responsible for the IL-12p70 production of DC induced by OK432. Moreover, our data suggest that the ligand triggering IL-12p70 secretion upon TLR3 stimulation is sensitive to proteinase and partly also RNAse treatment. The fact that a bacterial compound like OK432 can activate the TLR3 pathway in human DC is a novel finding. OK432 demonstrates a critical ability to induce IL-12p70 production, which is of great relevance in DC based cancer immunotherapy.

The Bacterial Preparation OK432 Induces IL-12p70 Secretion in Human Dendritic Cells in a TLR3 Dependent Manner

PubMed Central

Hovden, Arnt-Ove; Karlsen, Marie; Jonsson, Roland; Appel, Silke

2012-01-01

Dendritic cells (DC) used in therapeutic cancer immunotherapy have to be able to stimulate T cells resulting in an immune response that can efficiently target the cancer cells. One of the critical hurdles has been the lack of IL-12p70 production when maturating the DC, which is rectified by using the bacterial preparation OK432 (trade name Picibanil) to mature the cells. In order to identify the mechanism behind OK432 stimulation of DC, we investigated the contribution of different TLR to examine their involvement in IL-12p70 production. By combining different inhibitors of TLR signaling, we demonstrate here that TLR3 is responsible for the IL-12p70 production of DC induced by OK432. Moreover, our data suggest that the ligand triggering IL-12p70 secretion upon TLR3 stimulation is sensitive to proteinase and partly also RNAse treatment. The fact that a bacterial compound like OK432 can activate the TLR3 pathway in human DC is a novel finding. OK432 demonstrates a critical ability to induce IL-12p70 production, which is of great relevance in DC based cancer immunotherapy. PMID:22363584

Ophthalmic community perception of new medication needs.

PubMed

Stewart, William C; Stewart, Jeanette A; Nelson, Lindsay A

2018-01-01

To survey ophthalmologists (who have participated previously in clinical research) and ophthalmic industry professionals (who have been involved in ocular research and development) to indicate perceived needs for new pharmaceuticals in various ophthalmic subspecialties. A prospective, industry-based survey was sent to ophthalmologists and ophthalmic industry professionals about the perceived needs for new pharmaceutical products. This survey was sent to 559 ophthalmic pharma professionals and ophthalmologists. We received 82 (15%) responses. The results showed that the most commonly perceived need for new pharmaceuticals were dry and wet age-related macular degeneration, glaucoma, diabetic macular edema and dry eye. There was a statistical difference found between response groups ( P <0.0001). Respondents indicated they would express their commitment to a new product they perceived as needed by recommending to colleagues (63%), prescribing (60%), participating as principle investigator in a related clinical trial (52%), advising the company (52%), lecturing on behalf of the product (43%), investing in the product (38%), taking no action (7%) or obtain a position in the company (1%). Ophthalmic pharma professionals and ophthalmologists perceive the greatest need for new medicines in ophthalmology to be in dry and wet age-related macular degeneration, glaucoma, diabetic macular edema and dry eye.

The corporate determinants of health: how big business affects our health, and the need for government action!

PubMed

Millar, John S

2013-05-14

Corporations have a great effect on the health of Canadians.Good companies create jobs, sell valued products at market value, pay a living wage, empower employees, have progressive human resource policies (parental, mental health leaves, workplace wellness programs, day care), and pay their appropriate corporate taxes. They embrace corporate social responsibility and some have a triple bottom line - people, planet and profits. More good corporations are needed.But others are selling products that are damaging to health and the environment, at prices that do not account for these damaging effects and often target consumers that are ill-informed and susceptible (e.g., children). These include businesses involving tobacco, alcohol, drugs, junk foods and beverages, resource extraction, arms production and the electronic media.Governments have a responsibility to take action when the market mechanism fails in this way.A priority for action is the food and beverage sector. The overconsumption of sugar, fat and salt is causing a rising prevalence of all the major chronic diseases, rising health care costs and declining population health and productivity. Urgent government action is required: taxation, advertising and sales restrictions, and a salt reduction program.

Liability concerns in contraceptive research and development.

PubMed

Segal, S J

1999-12-01

The history of liability claims in the US against contraceptive products is among the issues that discourage manufacturers from investing in discovery and development in this field. Other factors are the high cost of new drug development, elevated insurance rates for contraceptives, and the desire to avoid controversy that can disturb corporate tranquility. General features of the American legal system influence the large number and cost of product liability claims in the US compared to Europe. These differences pertain to issues such as the role of judges, how lawyers receive their compensation, and the use of expert scientific testimony. The history of litigation in the US against pharmaceutical products and devices pertaining to women's health suggests that interventions that involve the reproductive system are held to different standards or elicit different emotional responses than other pharmaceutical products or devices.

Production of endogenous pyrogen.

PubMed

Dinarello, C A

1979-01-01

The production and release of endogenous pyrogen by the host is the first step in the pathogenesis of fever. Endogenous pyrogen is a low-molecular-weight protein released from phagocytic leukocytes in response to several substances of diverse nature. Some of these agents stimulate production of endogenous pyrogen because they are toxic; others act as antigens and interact with either antibody or sensitized lymphocytes in order to induce its production. Some tumors of macrophage origin produce the molecule spontaneously. Whatever the mechanism involved, endogenous pyrogen is synthesized following transcription of new DNA and translation of mRNA into new protein. Once synthesis is completed, the molecule is released without significant intracellular storage. Recent evidence suggests that following release, molecular aggregates form which are biologically active. In its monomer form, endogenous pyrogen is a potent fever-producing substance and mediates fever by its action on the thermoregulatory center.

Neuroendocrine Factors in the Regulation of Inflammation: Excessive Adiposity and Calorie Restriction

PubMed Central

Fontana, Luigi

2009-01-01

Acute inflammation is usually a self-limited life preserving response, triggered by pathogens and/or traumatic injuries. This transient response normally leads to removal of harmful agents and to healing of the damaged tissues. In contrast, unchecked or chronic inflammation can lead to persistent tissue and organ damage by activated leukocytes, cytokines, or collagen deposition. Excessive energy intake and adiposity cause systemic inflammation, whereas calorie restriction without malnutrition exerts a potent anti-inflammatory effect. As individuals accumulate fat and their adipocytes enlarge, adipose tissue undergoes molecular and cellular alterations, macrophages accumulate, and inflammation ensues. Overweight/obese subjects have significantly higher plasma concentrations of C-reactive protein and several cytokines, including IL-6, IL-8, IL-18, and TNF-alpha. Experimental animals on a chronic CR regimen, instead, have low levels of circulating inflammatory cytokines, low blood lymphocyte levels, reduced production of inflammatory cytokines by the white blood cells in response to stimulation, and cortisol levels in the high normal range. Recent data demonstrate that CR exerts a powerful anti-inflammatory effect also in non-human primates and humans. Multiple metabolic and neuroendocrine mechanisms are responsible for the CR-mediated anti-inflammatory effects, including reduced adiposity and secretion of pro-inflammatory adipokines, enhanced glucocorticoid production, reduced plasma glucose and advanced glycation end-product concentrations, increased parasympathetic tone, and increased ghrelin production. Measuring tissue specific effects of CR using genomic, proteomic and metabolomic techniques in humans will foster the understanding of the complex biological processes involved in the anti-inflammatory and anti-aging effects of CR. PMID:18502597

Staurosporine, but not Ro 31-8220, induces interleukin 2 production and synergizes with interleukin 1alpha in EL4 thymoma cells.

PubMed

Mahon, T M; Matthews, J S; O'Neill, L A

1997-07-01

Protein kinase C (PKC) has been implicated in interleukin 1 (IL1) signal transduction in a number of cellular systems, either as a key event in IL1 action or as a negative regulator. Here we have examined the effects of two PKC inhibitors, staurosporine and the more selective agent Ro 31-8220, on IL1 responses in the murine thymoma line EL4.NOB-1. A 1 h pulse of staurosporine was found to strongly potentiate the induction of IL2 by IL1alpha in these cells. In contrast, neither a pulse nor prolonged incubation with Ro 31-8220 affected the response to IL1alpha. Both agents blocked the response to PMA, however. A 1 h pulse of staurosporine was also found to induce IL2 production on its own, activate the transcription factor nuclear factor kappaB (NFkappaB) and increase the expression of a NFkappaB-linked reporter gene. It synergized with IL1alpha in all of these responses. Ro 31-8220 was again without effect, although both staurosporine and Ro 31-8220 blocked the activation of NFkappaB by PMA. Finally, staurosporine caused the translocation of PKC-alpha and -epsilon, and to a lesser extent PKC-beta, but not PKC-θ or -zeta, from the cytosol to the membrane, although a similar effect was observed with Ro 31-8220. The results suggest that PKC is not involved in IL1alpha signalling in EL4 cells. Furthermore, the potentiating effect of staurosporine on IL1alpha action does not involve PKC inhibition, and is likely to be at the level of NFkappaB activation.

Dynamic Maize Responses to Aphid Feeding Are Revealed by a Time Series of Transcriptomic and Metabolomic Assays1[OPEN

PubMed Central

Tzin, Vered; Fernandez-Pozo, Noe; Richter, Annett; Schmelz, Eric A.; Schoettner, Matthias; Schäfer, Martin; Ahern, Kevin R.; Meihls, Lisa N.; Kaur, Harleen; Huffaker, Alisa; Mori, Naoki; Degenhardt, Joerg; Mueller, Lukas A.; Jander, Georg

2015-01-01

As a response to insect attack, maize (Zea mays) has inducible defenses that involve large changes in gene expression and metabolism. Piercing/sucking insects such as corn leaf aphid (Rhopalosiphum maidis) cause direct damage by acquiring phloem nutrients as well as indirect damage through the transmission of plant viruses. To elucidate the metabolic processes and gene expression changes involved in maize responses to aphid attack, leaves of inbred line B73 were infested with corn leaf aphids for 2 to 96 h. Analysis of infested maize leaves showed two distinct response phases, with the most significant transcriptional and metabolic changes occurring in the first few hours after the initiation of aphid feeding. After 4 d, both gene expression and metabolite profiles of aphid-infested maize reverted to being more similar to those of control plants. Although there was a predominant effect of salicylic acid regulation, gene expression changes also indicated prolonged induction of oxylipins, although not necessarily jasmonic acid, in aphid-infested maize. The role of specific metabolic pathways was confirmed using Dissociator transposon insertions in maize inbred line W22. Mutations in three benzoxazinoid biosynthesis genes, Bx1, Bx2, and Bx6, increased aphid reproduction. In contrast, progeny production was greatly decreased by a transposon insertion in the single W22 homolog of the previously uncharacterized B73 terpene synthases TPS2 and TPS3. Together, these results show that maize leaves shift to implementation of physical and chemical defenses within hours after the initiation of aphid feeding and that the production of specific metabolites can have major effects in maize-aphid interactions. PMID:26378100

Efficient block preconditioned eigensolvers for linear response time-dependent density functional theory

NASA Astrophysics Data System (ADS)

Vecharynski, Eugene; Brabec, Jiri; Shao, Meiyue; Govind, Niranjan; Yang, Chao

2017-12-01

We present two efficient iterative algorithms for solving the linear response eigenvalue problem arising from the time dependent density functional theory. Although the matrix to be diagonalized is nonsymmetric, it has a special structure that can be exploited to save both memory and floating point operations. In particular, the nonsymmetric eigenvalue problem can be transformed into an eigenvalue problem that involves the product of two matrices M and K. We show that, because MK is self-adjoint with respect to the inner product induced by the matrix K, this product eigenvalue problem can be solved efficiently by a modified Davidson algorithm and a modified locally optimal block preconditioned conjugate gradient (LOBPCG) algorithm that make use of the K-inner product. The solution of the product eigenvalue problem yields one component of the eigenvector associated with the original eigenvalue problem. We show that the other component of the eigenvector can be easily recovered in an inexpensive postprocessing procedure. As a result, the algorithms we present here become more efficient than existing methods that try to approximate both components of the eigenvectors simultaneously. In particular, our numerical experiments demonstrate that the new algorithms presented here consistently outperform the existing state-of-the-art Davidson type solvers by a factor of two in both solution time and storage.

The importance of ribosome production, and the 5S RNP-MDM2 pathway, in health and disease.

PubMed

Pelava, Andria; Schneider, Claudia; Watkins, Nicholas J

2016-08-15

Ribosomes are abundant, large RNA-protein complexes that are the source of all protein synthesis in the cell. The production of ribosomes is an extremely energetically expensive cellular process that has long been linked to human health and disease. More recently, it has been shown that ribosome biogenesis is intimately linked to multiple cellular signalling pathways and that defects in ribosome production can lead to a wide variety of human diseases. Furthermore, changes in ribosome production in response to nutrient levels in the diet lead to metabolic re-programming of the liver. Reduced or abnormal ribosome production in response to cellular stress or mutations in genes encoding factors critical for ribosome biogenesis causes the activation of the tumour suppressor p53, which leads to re-programming of cellular transcription. The ribosomal assembly intermediate 5S RNP (ribonucleoprotein particle), containing RPL5, RPL11 and the 5S rRNA, accumulates when ribosome biogenesis is blocked. The excess 5S RNP binds to murine double minute 2 (MDM2), the main p53-suppressor in the cell, inhibiting its function and leading to p53 activation. Here, we discuss the involvement of ribosome biogenesis in the homoeostasis of p53 in the cell and in human health and disease. © 2016 The Author(s).

Conserved and Differential Effects of Dietary Energy Intake on the Hippocampal Transcriptomes of Females and Males

PubMed Central

Martin, Bronwen; Pearson, Michele; Brenneman, Randall; Golden, Erin; Keselman, Alex; Iyun, Titilola; Carlson, Olga D.; Egan, Josephine M.; Becker, Kevin G.; Wood, William; Prabhu, Vinayakumar; de Cabo, Rafael

2008-01-01

The level of dietary energy intake influences metabolism, reproductive function, the development of age-related diseases, and even cognitive behavior. Because males and females typically play different roles in the acquisition and allocation of energy resources, we reasoned that dietary energy intake might differentially affect the brains of males and females at the molecular level. To test this hypothesis, we performed a gene array analysis of the hippocampus in male and female rats that had been maintained for 6 months on either ad libitum (control), 20% caloric restriction (CR), 40% CR, intermittent fasting (IF) or high fat/high glucose (HFG) diets. These diets resulted in expected changes in body weight, and circulating levels of glucose, insulin and leptin. However, the CR diets significantly increased the size of the hippocampus of females, but not males. Multiple genes were regulated coherently in response to energy restriction diets in females, but not in males. Functional physiological pathway analyses showed that the 20% CR diet down-regulated genes involved in glycolysis and mitochondrial ATP production in males, whereas these metabolic pathways were up-regulated in females. The 40% CR diet up-regulated genes involved in glycolysis, protein deacetylation, PGC-1α and mTor pathways in both sexes. IF down-regulated many genes in males including those involved in protein degradation and apoptosis, but up-regulated many genes in females including those involved in cellular energy metabolism, cell cycle regulation and protein deacetylation. Genes involved in energy metabolism, oxidative stress responses and cell death were affected by the HFG diet in both males and females. The gender-specific molecular genetic responses of hippocampal cells to variations in dietary energy intake identified in this study may mediate differential behavioral responses of males and females to differences in energy availability. PMID:18545695

Immunologic response and memory T cells in subjects cured of tegumentary leishmaniasis.

PubMed

Carvalho, Augusto M; Magalhães, Andréa; Carvalho, Lucas P; Bacellar, Olívia; Scott, Phillip; Carvalho, Edgar M

2013-11-09

The main clinical forms of tegumentary leishmaniasis are cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML). L.braziliensis infection is characterized by an exaggerated production of IFN-gamma and TNF-alpha, cytokines involved in parasite destruction, but also in the pathology. Maintenance of an antigen-specific immune response may be important for resistance to re-infection and will contribute for vaccine development. In the present work we investigated the immune response in CL and ML cured individuals. Participants in the present study included 20 CL and 20 ML patients, who were evaluated prior to, as well as 2 to 15 years after therapy. IFN-gamma, IL-2 and TNF-alpha production were determined by ELISA in supernatants of mononuclear cells stimulated with soluble L.braziliensis antigen (SLA). The frequency of memory CD4+ T cell populations was determined by FACS. Here we show that the majority of CL and ML patients did not produce in vitro IFN-gamma in response to SLA after cure. In the cured individuals who responded to SLA, effector memory (CD45RA-CCR7-) CD4+ T cells were the ones producing IFN-gamma. Because a large percent of CL and ML cured patients lost SLA-induced IFN-gamma production in peripheral blood, we performed Leishmania skin test (LST). A positive LST was found in 87.5% and 100% of CL and ML cured individuals, respectively, who did not produce IFN-gamma or IL-2 in vitro. This study shows that in spite of losing in vitro antigen-specific response to Leishmania, cured CL and ML subjects retain the ability to respond to SLA in vivo. These findings indicate that LST, rather than IFN-gamma production, may be a better assessment of lasting immunity to leishmaniasis in human studies, and thus a better tool for assessing immunization after vaccine. Furthermore, in cured individuals which maintains Leishmania-specific IFN-gamma production, effector memory CD4+ T cells were the main source of this cytokine.

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

Immunological responses to semen in the female genital tract.

PubMed

Schuberth, H J; Taylor, U; Zerbe, H; Waberski, D; Hunter, R; Rath, D

2008-11-01

When spermatozoa, seminal plasma and semen extender reach the uterus and interact with local leukocytes and endometrial cells, several immune mechanisms are initiated which have immediate, mid-term and long-term effects on ovulation, sperm cell selection, fertilization and pregnancy success by assuring the acceptance of fetal tissues. This report gives an overview on relevant key immune mechanisms following roughly the time axis after insemination. Detailed knowledge regarding these mechanisms will aid maximizing reproductive efficiency in livestock production. In the future, the many species involved will require a more comparative approach, since evidence is growing that endometrial physiology and the response to varying amounts and compositions of seminal plasma, various semen extenders, and variable numbers of spermatozoa also provoke different immune responses.

Investigating Proteome and Transcriptome Defense Response of Apples Induced by Yarrowia lipolytica.

PubMed

Zhang, Hongyin; Chen, Liangliang; Sun, Yiwen; Zhao, Lina; Zheng, Xiangfeng; Yang, Qiya; Zhang, Xiaoyun

2017-04-01

A better understanding of the mode of action of postharvest biocontrol agents on fruit surfaces is critical for the advancement of successful implementation of postharvest biocontrol products. This is due to the increasing importance of biological control of postharvest diseases over chemical and other control methods. However, most of the mechanisms involved in biological control remain unknown and need to be explored. Yarrowia lipolytica significantly inhibited blue mold decay of apples caused by Penicillium expansum. The findings also demonstrated that Y. lipolytica stimulated the activities of polyphenoloxidase, peroxidase, chitinase, l-phenylalanine ammonia lyase involved in enhancing defense responses in apple fruit tissue. Proteomic and transcriptomic analysis revealed a total of 35 proteins identified as up- and down-regulated in response to the Y. lipolytica inducement. These proteins were related to defense, biotic stimulus, and stress responses, such as pathogenesis-related proteins and dehydrin. The analysis of the transcriptome results proved that the induced resistance was mediated by a crosstalk between salicylic acid (SA) and ethylene/jasmonate (ET/JA) pathways. Y. lipolytica treatment activated the expression of isochorismate synthase gene in the SA pathway, which up-regulates the expression of PR4 in apple. The expression of 1-aminocyclopropane-1-carboxylate oxidase gene and ET-responsive transcription factors 2 and 4, which are involved in the ET pathway, were also activated. In addition, cytochrome oxidase I, which plays an important role in JA signaling for resistance acquisition, was also activated. However, not all of the genes had a positive effect on the SA and ET/JA signal pathways. As transcriptional repressors in JA signaling, TIFY3B and TIFY11B were triggered by the yeast, but the gene expression levels were relatively low. Taken together, Y. lipolytica induced the SA and ET/JA signal mediating the defense pathways by stimulating defense response genes, such as peroxidase, thaumatin-like protein, and chitinase 4-like, which are involved in defense response in apple. [Formula: see text] Copyright © 2017 The Author(s) This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

[Productive social activities in mothers of intellectually disabled children moderate the relationship between caregiver burden and self-rated health].

PubMed

Yatsugi, Sawa; Suzukamo, Yoshimi; Izumi, Sinichi

2013-07-01

Recently, the length of time for which intellectually disabled children receive homecare has increased; hence, the mothers caring for these intellectually disabled children at home are being exposed to increasingly heavy caregiver burden. Previous studies have reported that negative psychological states, including caregiver burden, influence self-rated health status; however, when elderly people engaged in productive social activities, they experienced heightened positive psychological states. Therefore, the objective of this study was to investigate whether mothers' participation in productive social activities influenced the relationship between caregiver burden and self-rated health status. We performed a cross-sectional study using a questionnaire that included items on self-rated health, the modified Japanese version of the Zarit Caregiver Burden Interview, productive social activities, and various confounding variables. We sent the questionnaires to 270 mothers belonging to patient and family advocacy groups. We then compared the self-rated health and caregiver burden between a group of mothers involved in productive social activities and a group not involved in such activities. The relationships between self-rated health, caregiver burden, and productive social activities were analyzed using analysis of variance (ANOVA) and post-hoc testing. We obtained 120 valid responses. Mothers with greater burden had worse self-rated health than the other group (r=-0.305). According to the ANOVA results, the self-rated health of mothers involved in productive social activities did not significantly differ between caregiver burden groups (mild burden group: 3.4 vs. severe burden group: 3.12; F=1.3, P=.253), whereas the self-rated health of mothers without productive social activities showed a significant difference between caregiver burden groups (mild burden group: 3.4 vs. severe burden group: 2.7; F=5.6, P=.017). Mothers with greater burden had worse self-rated health. However, in mothers who were engaged in productive social activities, self-rated health did not differ between the mild burden and severe burden groups. Therefore, productive social activities can favorably moderate the relationship between caregiver burden and self-rated health.

Functional Requirements for DjlA- and RraA-Mediated Enhancement of Recombinant Membrane Protein Production in the Engineered Escherichia coli Strains SuptoxD and SuptoxR.

PubMed

Gialama, Dimitra; Delivoria, Dafni Chrysanthi; Michou, Myrsini; Giannakopoulou, Artemis; Skretas, Georgios

2017-06-16

In previous work, we have generated the engineered Escherichia coli strains SuptoxD and SuptoxR, which upon co-expression of the effector genes djlA or rraA, respectively, are capable of suppressing the cytotoxicity caused by membrane protein (MP) overexpression and of producing dramatically enhanced yields for a variety of recombinant MPs of both prokaryotic and eukaryotic origin. Here, we investigated the functional requirements for DnaJ-like protein A (DjlA)- and regulator of ribonuclease activity A (RraA)-mediated enhancement of recombinant MP production in these strains and show that: (i) DjlA and RraA act independently, that is, the beneficial effects of each protein on recombinant MP production occur through a mechanism that does not involve the other, and in a non-additive manner; (ii) full-length and membrane-bound DjlA is required for exerting its beneficial effects on recombinant MP production in E. coli SuptoxD; (iii) the MP production-promoting properties of DjlA in SuptoxD involve the action of the molecular chaperone DnaK but do not rely on the activation of the regulation of capsular synthesis response, a well-established consequence of djlA overexpression; (iv) the observed RraA-mediated effects in E. coli SuptoxR involve the ribonucleolytic activity of RNase E, but not that of its paralogous ribonuclease RNase G; and (v) DjlA and RraA are unique among similar E. coli proteins in their ability to promote bacterial recombinant MP production. These observations provide important clues about the molecular requirements for suppressed toxicity and enhanced MP accumulation in SuptoxD/SuptoxR and will guide future studies aiming to decipher the exact mechanism of DjlA- and RraA-mediated enhancement of recombinant MP production in these strains. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mitochondrial transcription factor A serves as a danger signal by augmenting plasmacytoid dendritic cell responses to DNA.

PubMed

Julian, Mark W; Shao, Guohong; Bao, Shengying; Knoell, Daren L; Papenfuss, Tracey L; VanGundy, Zachary C; Crouser, Elliott D

2012-07-01

Plasmacytoid dendritic cells (pDC) are potent APCs known to regulate immune responses to self-Ags, particularly DNA. The mitochondrial fraction of necrotic cells was found to most potently promote human pDC activation, as reflected by type I IFN release, which was dependent upon the presence of mitochondrial DNA and involved TLR9 and receptors for advanced glycation end products. Mitochondrial transcription factor A (TFAM), a highly abundant mitochondrial protein that is functionally and structurally homologous to high mobility group box protein 1, was observed to synergize with CpG-containing oligonucleotide, type A, DNA to promote human pDC activation. pDC type I IFN responses to TFAM and CpG-containing oligonucleotide, type A, DNA indicated their engagement with receptors for advanced glycation end products and TLR9, respectively, and were dependent upon endosomal processing and PI3K, ERK, and NF-κB signaling. Taken together, these results indicate that pDC contribute to sterile immune responses by recognizing the mitochondrial component of necrotic cells and further incriminate TFAM and mitochondrial DNA as likely mediators of pDC activation under these circumstances.

Methanol induces cytosolic calcium variations, membrane depolarization and ethylene production in arabidopsis and tobacco.

PubMed

Tran, Daniel; Dauphin, Aurélien; Meimoun, Patrice; Kadono, Takashi; Nguyen, Hieu T H; Arbelet-Bonnin, Delphine; Zhao, Tingting; Errakhi, Rafik; Lehner, Arnaud; Kawano, Tomonori; Bouteau, François

2018-03-20

Methanol is a volatile organic compound released from plants through the action of pectin methylesterases (PMEs), which demethylesterify cell wall pectins. Plant PMEs play a role in developmental processes but also in responses to herbivory and infection by fungal or bacterial pathogens. However, molecular mechanisms that explain how methanol could affect plant defences remain poorly understood. Using cultured cells and seedlings from Arabidopsis thaliana and tobacco BY2 expressing the apoaequorin gene, allowing quantification of cytosolic Ca2+, a reactive oxygen species (ROS) probe (CLA, Cypridina luciferin analogue) and electrophysiological techniques, we followed early plant cell responses to exogenously supplied methanol applied as a liquid or as volatile. Methanol induces cytosolic Ca2+ variations that involve Ca2+ influx through the plasma membrane and Ca2+ release from internal stores. Our data further suggest that these Ca2+ variations could interact with different ROS and support a signalling pathway leading to well known plant responses to pathogens such as plasma membrane depolarization through anion channel regulation and ethylene synthesis. Methanol is not only a by-product of PME activities, and our data suggest that [Ca2+]cyt variations could participate in signalling processes induced by methanol upstream of plant defence responses.

The Arabidopsis mutant cev1 links cell wall signaling to jasmonate and ethylene responses.

PubMed

Ellis, Christine; Karafyllidis, Ioannis; Wasternack, Claus; Turner, John G

2002-07-01

Biotic and abiotic stresses stimulate the synthesis of jasmonates and ethylene, which, in turn, induce the expression of genes involved in stress response and enhance defense responses. The cev1 mutant has constitutive expression of stress response genes and has enhanced resistance to fungal pathogens. Here, we show that cev1 plants have increased production of jasmonate and ethylene and that its phenotype is suppressed by mutations that interrupt jasmonate and ethylene signaling. Genetic mapping, complementation analysis, and sequence analysis revealed that CEV1 is the cellulose synthase CeSA3. CEV1 was expressed predominantly in root tissues, and cev1 roots contained less cellulose than wild-type roots. Significantly, the cev1 mutant phenotype could be reproduced by treating wild-type plants with cellulose biosynthesis inhibitors, and the cellulose synthase mutant rsw1 also had constitutive expression of VSP. We propose that the cell wall can signal stress responses in plants.

THE ROLE OF THE CONSEQUENCE MANAGEMENT HOME TEAM IN THE FUKUSHIMA DAIICHI RESPONSE

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

Pemberton, Wendy; Mena, RaJah; Beal, William

The Consequence Management Home Team is a U.S. Department of Energy/National Nuclear Security Administration asset. It assists a variety of response organizations with modeling; radiological operations planning; field monitoring techniques; and the analysis, interpretation, and distribution of radiological data. These reach-back capabilities are activated quickly to support public safety and minimize the social and economic impact of a nuclear or radiological incident. In the Fukushima Daiichi response, the Consequence Management Home Team grew to include a more broad range of support than was historically planned. From the early days of the response to the continuing involvement in supporting late phasemore » efforts, each stage of the Consequence Management Home Team support had distinct characteristics in terms of management of incoming data streams as well as creation of products. Regardless of stage, the Consequence Management Home Team played a critical role in the Fukushima Daiichi response effort.« less

Glucocorticoids facilitate the transcription from the human cytomegalovirus major immediate early promoter in glucocorticoid receptor- and nuclear factor-I-like protein-dependent manner

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

Inoue-Toyoda, Maki; Kato, Kohsuke; Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575

Human cytomegalovirus (HCMV) is a common and usually asymptomatic virus agent in healthy individuals. Initiation of HCMV productive infection depends on expression of the major immediate early (MIE) genes. The transcription of HCMV MIE genes is regulated by a diverse set of transcription factors. It was previously reported that productive HCMV infection is triggered probably by elevation of the plasma hydroxycorticoid level. However, it is poorly understood whether the transcription of MIE genes is directly regulated by glucocorticoid. Here, we found that the dexamethasone (DEX), a synthetic glucocorticoid, facilitates the transcription of HCMV MIE genes through the MIE promoter andmore » enhancer in a glucocorticoid receptor (GR)-dependent manner. By competitive EMSA and reporter assays, we revealed that an NF-I like protein is involved in DEX-mediated transcriptional activation of the MIE promoter. Thus, this study supports a notion that the increased level of hydroxycorticoid in the third trimester of pregnancy reactivates HCMV virus production from the latent state. - Highlights: • DEX facilitates the transcription from the HCMV MIE promoter. • GR is involved in DEX-dependent transcription from the HCMV MIE promoter. • A 17 bp repeat is responsible for the HCMV MIE promoter activation by DEX. • An NF-I-like protein is involved in the HCMV MIE promoter activation by DEX.« less

The Mucosal Adjuvant Cholera Toxin B Instructs Non-Mucosal Dendritic Cells to Promote IgA Production Via Retinoic Acid and TGF-β

PubMed Central

Gloudemans, Anouk K.; Plantinga, Maud; Guilliams, Martin; Willart, Monique A.; Ozir-Fazalalikhan, Arifa; van der Ham, Alwin; Boon, Louis; Harris, Nicola L.; Hammad, Hamida; Hoogsteden, Henk C.; Yazdanbakhsh, Maria; Hendriks, Rudi W.

2013-01-01

It is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA), and how T cell-dependent (TD) or -independent (TI) pathways might be involved. Mucosal dendritic cells (DCs) are the primary antigen presenting cells driving TI IgA synthesis, by producing a proliferation-inducing ligand (APRIL), B cell activating factor (BAFF), Retinoic Acid (RA), TGF-β or nitric oxide (NO). We hypothesized that the mucosal adjuvant Cholera Toxin subunit B (CTB) could imprint non-mucosal DCs to induce IgA synthesis, and studied the mechanism of its induction. In vitro, CTB-treated bone marrow derived DCs primed for IgA production by B cells without the help of T cells, yet required co-signaling by different Toll-like receptor (TLR) ligands acting via the MyD88 pathway. CTB-DC induced IgA production was blocked in vitro or in vivo when RA receptor antagonist, TGF-β signaling inhibitor or neutralizing anti-TGF-β was added, demonstrating the involvement of RA and TGF-β in promoting IgA responses. There was no major involvement for BAFF, APRIL or NO. This study highlights that synergism between CTB and MyD88-dependent TLR signals selectively imprints a TI IgA-inducing capacity in non-mucosal DCs, explaining how CTB acts as an IgA promoting adjuvant. PMID:23527272

The mucosal adjuvant cholera toxin B instructs non-mucosal dendritic cells to promote IgA production via retinoic acid and TGF-β.

PubMed

Gloudemans, Anouk K; Plantinga, Maud; Guilliams, Martin; Willart, Monique A; Ozir-Fazalalikhan, Arifa; van der Ham, Alwin; Boon, Louis; Harris, Nicola L; Hammad, Hamida; Hoogsteden, Henk C; Yazdanbakhsh, Maria; Hendriks, Rudi W; Lambrecht, Bart N; Smits, Hermelijn H

2013-01-01

It is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA), and how T cell-dependent (TD) or -independent (TI) pathways might be involved. Mucosal dendritic cells (DCs) are the primary antigen presenting cells driving TI IgA synthesis, by producing a proliferation-inducing ligand (APRIL), B cell activating factor (BAFF), Retinoic Acid (RA), TGF-β or nitric oxide (NO). We hypothesized that the mucosal adjuvant Cholera Toxin subunit B (CTB) could imprint non-mucosal DCs to induce IgA synthesis, and studied the mechanism of its induction. In vitro, CTB-treated bone marrow derived DCs primed for IgA production by B cells without the help of T cells, yet required co-signaling by different Toll-like receptor (TLR) ligands acting via the MyD88 pathway. CTB-DC induced IgA production was blocked in vitro or in vivo when RA receptor antagonist, TGF-β signaling inhibitor or neutralizing anti-TGF-β was added, demonstrating the involvement of RA and TGF-β in promoting IgA responses. There was no major involvement for BAFF, APRIL or NO. This study highlights that synergism between CTB and MyD88-dependent TLR signals selectively imprints a TI IgA-inducing capacity in non-mucosal DCs, explaining how CTB acts as an IgA promoting adjuvant.

Calpain-10 Activity Underlies Angiotensin II-Induced Aldosterone Production in an Adrenal Glomerulosa Cell Model

PubMed Central

Seremwe, Mutsa; Schnellmann, Rick G.

2015-01-01

Aldosterone is a steroid hormone important in the regulation of blood pressure. Aberrant production of aldosterone results in the development and progression of diseases including hypertension and congestive heart failure; therefore, a complete understanding of aldosterone production is important for developing more effective treatments. Angiotensin II (AngII) regulates steroidogenesis, in part through its ability to increase intracellular calcium levels. Calcium can activate calpains, proteases classified as typical or atypical based on the presence or absence of penta-EF-hands, which are involved in various cellular responses. We hypothesized that calpain, in particular calpain-10, is activated by AngII in adrenal glomerulosa cells and underlies aldosterone production. Our studies showed that pan-calpain inhibitors reduced AngII-induced aldosterone production in 2 adrenal glomerulosa cell models, primary bovine zona glomerulosa and human adrenocortical carcinoma (HAC15) cells, as well as CYP11B2 expression in the HAC15 cells. Although AngII induced calpain activation in these cells, typical calpain inhibitors had no effect on AngII-elicited aldosterone production, suggesting a lack of involvement of classical calpains in this process. However, an inhibitor of the atypical calpain, calpain-10, decreased AngII-induced aldosterone production. Consistent with this result, small interfering RNA (siRNA)-mediated knockdown of calpain-10 inhibited aldosterone production and CYP11B2 expression, whereas adenovirus-mediated overexpression of calpain-10 resulted in increased AngII-induced aldosterone production. Our results indicate that AngII-induced activation of calpain-10 in glomerulosa cells underlies aldosterone production and identify calpain-10 or its downstream pathways as potential targets for the development of drug therapies for the treatment of hypertension. PMID:25836666

Reactive oxygen species produced by NADPH oxidase and mitochondrial dysfunction in lung after an acute exposure to Residual Oil Fly Ashes

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

Magnani, Natalia D.; Marchini, Timoteo; Vanasco, Virginia

2013-07-01

Reactive O{sub 2} species production triggered by particulate matter (PM) exposure is able to initiate oxidative damage mechanisms, which are postulated as responsible for increased morbidity along with the aggravation of respiratory diseases. The aim of this work was to quantitatively analyse the major sources of reactive O{sub 2} species involved in lung O{sub 2} metabolism after an acute exposure to Residual Oil Fly Ashes (ROFAs). Mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight), and lung samples were analysed 1 h after instillation. Tissue O{sub 2} consumption and NADPH oxidase (Nox) activity were evaluated in tissuemore » homogenates. Mitochondrial respiration, respiratory chain complexes activity, H{sub 2}O{sub 2} and ATP production rates, mitochondrial membrane potential and oxidative damage markers were assessed in isolated mitochondria. ROFA exposure was found to be associated with 61% increased tissue O{sub 2} consumption, a 30% increase in Nox activity, a 33% increased state 3 mitochondrial O{sub 2} consumption and a mitochondrial complex II activity increased by 25%. During mitochondrial active respiration, mitochondrial depolarization and a 53% decreased ATP production rate were observed. Neither changes in H{sub 2}O{sub 2} production rate, nor oxidative damage in isolated mitochondria were observed after the instillation. After an acute ROFA exposure, increased tissue O{sub 2} consumption may account for an augmented Nox activity, causing an increased O{sub 2}{sup ·−} production. The mitochondrial function modifications found may prevent oxidative damage within the organelle. These findings provide new insights to the understanding of the mechanisms involving reactive O{sub 2} species production in the lung triggered by ROFA exposure. - Highlights: • Exposure to ROFA alters the oxidative metabolism in mice lung. • The augmented Nox activity contributes to the high tissue O{sub 2} consumption. • Exposure to ROFA produces alterations in mitochondrial function. • ΔΨ{sub m} decrease in state 3 may be responsible for the decreased ATP production. • Mild uncoupling prevents mitochondrial oxidative damage.« less

Blockchain Based Decentralized Management of Demand Response Programs in Smart Energy Grids

PubMed Central

Pop, Claudia; Cioara, Tudor; Antal, Marcel; Anghel, Ionut; Salomie, Ioan; Bertoncini, Massimo

2018-01-01

In this paper, we investigate the use of decentralized blockchain mechanisms for delivering transparent, secure, reliable, and timely energy flexibility, under the form of adaptation of energy demand profiles of Distributed Energy Prosumers, to all the stakeholders involved in the flexibility markets (Distribution System Operators primarily, retailers, aggregators, etc.). In our approach, a blockchain based distributed ledger stores in a tamper proof manner the energy prosumption information collected from Internet of Things smart metering devices, while self-enforcing smart contracts programmatically define the expected energy flexibility at the level of each prosumer, the associated rewards or penalties, and the rules for balancing the energy demand with the energy production at grid level. Consensus based validation will be used for demand response programs validation and to activate the appropriate financial settlement for the flexibility providers. The approach was validated using a prototype implemented in an Ethereum platform using energy consumption and production traces of several buildings from literature data sets. The results show that our blockchain based distributed demand side management can be used for matching energy demand and production at smart grid level, the demand response signal being followed with high accuracy, while the amount of energy flexibility needed for convergence is reduced. PMID:29315250

The consistent differential expression of genetic pathways following exposure of an industrial Pseudomonas aeruginosa strain to preservatives and a laundry detergent formulation.

PubMed

Green, Angharad E; Amézquita, Alejandro; Le Marc, Yvan; Bull, Matthew J; Connor, Thomas R; Mahenthiralingam, Eshwar

2018-05-01

Pseudomonas aeruginosa is a common contaminant associated with product recalls in the home and personal care industry. Preservation systems are used to prevent spoilage and protect consumers, but greater knowledge is needed of preservative resistance mechanisms used by P. aeruginosa contaminants. We aimed to identify genetic pathways associated with preservative exposure by using an industrial P. aeruginosa strain and implementing RNA-Seq to understand gene expression changes in response to industry relevant conditions. The consistent differential expression of five genetic pathways during exposure to multiple industrial growth conditions associated with benzisothiazolone (BIT) and phenoxyethanol (POE) preservatives, and a laundry detergent (LD) formulation, was observed. A MexPQ-OpmE Resistance Nodulation Division efflux pump system was commonly upregulated in response to POE, a combination of BIT and POE, and LD together with BIT. In response to all industry conditions, a putative sialic acid transporter and isoprenoid biosynthesis gnyRDBHAL operon demonstrated consistent upregulation. Two operons phnBA and pqsEDCBA involved in Pseudomonas quinolone signaling production and quorum-sensing were also consistently downregulated during exposure to all the industry conditions. The ability to identify consistently differentially expressed genetic pathways in P. aeruginosa can inform the development of future targeted preservation systems that maintain product safety and minimise resistance development.

Proteins involved in difference of sorbitol fermentation rates of the toxigenic and nontoxigenic Vibrio cholerae El Tor strains revealed by comparative proteome analysis

PubMed Central

2009-01-01

Background The nontoxigenic V. cholerae El Tor strains ferment sorbitol faster than the toxigenic strains, hence fast-fermenting and slow-fermenting strains are defined by sorbitol fermentation test. This test has been used for more than 40 years in cholera surveillance and strain analysis in China. Understanding of the mechanisms of sorbitol metabolism of the toxigenic and nontoxigenic strains may help to explore the genome and metabolism divergence in these strains. Here we used comparative proteomic analysis to find the proteins which may be involved in such metabolic difference. Results We found the production of formate and lactic acid in the sorbitol fermentation medium of the nontoxigenic strain was earlier than of the toxigenic strain. We compared the protein expression profiles of the toxigenic strain N16961 and nontoxigenic strain JS32 cultured in sorbitol fermentation medium, by using fructose fermentation medium as the control. Seventy-three differential protein spots were found and further identified by MALDI-MS. The difference of product of fructose-specific IIA/FPR component gene and mannitol-1-P dehydrogenase, may be involved in the difference of sorbitol transportation and dehydrogenation in the sorbitol fast- and slow-fermenting strains. The difference of the relative transcription levels of pyruvate formate-lyase to pyruvate dehydrogenase between the toxigenic and nontoxigenic strains may be also responsible for the time and ability difference of formate production between these strains. Conclusion Multiple factors involved in different metabolism steps may affect the sorbitol fermentation in the toxigenic and nontoxigenic strains of V. cholerae El Tor. PMID:19589152

Can helminths or helminth-derived products be used in humans to prevent or treat allergic diseases?

PubMed

Erb, Klaus J

2009-02-01

Recent epidemiological and experimental data indicate that infection with helminths can protect humans from the development of allergic disorders by immunosuppressive mechanisms that involve the induction of IL-10 and/or regulatory T cells. Furthermore, helminth-derived immune modulators suppress allergic responses in mice. Trichuris suis therapy has been shown to be safe and efficacious in treating inflammatory bowel disease in humans. Has the time come to treat patients who have allergic diseases or healthy humans who are at risk of developing these diseases with helminths or helminth-derived products? Here, I discuss the pros and cons of such an approach.

Creativity and innovation by empowering the customer: The case of Mulino Bianco. Part II: The digital customer value added

NASA Astrophysics Data System (ADS)

Bujor, A.; Avasilcăi, S.

2015-11-01

The terms of creativity, co-creation, creative industries, innovation, and coinnovation are more and more used nowadays. While co-creation offers the possibility and encourages a more active involvement from the customers to create value rich experiences, innovation is responsible for the little improvements made for a better life, to grow a business, to improve products, services or company's productivity. Either customers, current and potential, or stakeholders’ involvement into innovation activities, through their creativity, represent an important way of value creation, of actions’ performance that increases the worth of goods, services, or business as a whole. More and more, different size businesses gather ideas for innovation from customers / stakeholders by involving them into the early stages of the innovation process. Actually, it has been shown that their ideas sketch their needs and wishes, and have been described as “need information”. Customers and stakeholders, in general, also offer ideas that have been called “solution information”, which represents, not only need information, but also customer-based proposals that describe how ideas can be transformed into marketable products. The term of creative industries refers to those goods that can technically be reproduced, industrially produced, and commercially sold, this being one of the many definitions found in the literature. Mulino Bianco was first launched in Italy, being one of the value brands of Barilla Group, which we can say, according to the Italian definition and classification, it belongs to creative industries: industry of food and taste. Even though Barilla Group's Research & Development department does its job very efficiently, developing and creating new products under different brands, lately a key strategy for the Group and for Mulino Bianco, by default, is customers’ pro-active involvement in products’ development or creation. One of the tools used for this is the Internet Toolkit and Web 2.0. by means of which customers are being invited to participate in competitions, being asked to design and share their concepts / views for new products, or to get involved in by voting those ideas they best like and would love to find them on markets. The aim of this paper is to explore and identify the involvement of stakeholders in Mullino Bianco's product development or improvement through creativity and innovation. As methodology approach, a case study about Mulino Bianco was done, and the foreseen result is highlighting the Nel Mulino Che Vorrei platform's features for consumer's engagement in the value creation and co-creation.

Quantitative proteomics and dynamic imaging of the nucleolus reveal distinct responses to UV and ionizing radiation.

PubMed

Moore, Henna M; Bai, Baoyan; Boisvert, François-Michel; Latonen, Leena; Rantanen, Ville; Simpson, Jeremy C; Pepperkok, Rainer; Lamond, Angus I; Laiho, Marikki

2011-10-01

The nucleolus is a nuclear organelle that coordinates rRNA transcription and ribosome subunit biogenesis. Recent proteomic analyses have shown that the nucleolus contains proteins involved in cell cycle control, DNA processing and DNA damage response and repair, in addition to the many proteins connected with ribosome subunit production. Here we study the dynamics of nucleolar protein responses in cells exposed to stress and DNA damage caused by ionizing and ultraviolet (UV) radiation in diploid human fibroblasts. We show using a combination of imaging and quantitative proteomics methods that nucleolar substructure and the nucleolar proteome undergo selective reorganization in response to UV damage. The proteomic responses to UV include alterations of functional protein complexes such as the SSU processome and exosome, and paraspeckle proteins, involving both decreases and increases in steady state protein ratios, respectively. Several nonhomologous end-joining proteins (NHEJ), such as Ku70/80, display similar fast responses to UV. In contrast, nucleolar proteomic responses to IR are both temporally and spatially distinct from those caused by UV, and more limited in terms of magnitude. With the exception of the NHEJ and paraspeckle proteins, where IR induces rapid and transient changes within 15 min of the damage, IR does not alter the ratios of most other functional nucleolar protein complexes. The rapid transient decrease of NHEJ proteins in the nucleolus indicates that it may reflect a response to DNA damage. Our results underline that the nucleolus is a specific stress response organelle that responds to different damage and stress agents in a unique, damage-specific manner.

Eosinophils Regulate Interferon Alpha Production in Plasmacytoid Dendritic Cells Stimulated with Components of Neutrophil Extracellular Traps.

PubMed

Skrzeczynska-Moncznik, Joanna; Zabieglo, Katarzyna; Bossowski, Jozef P; Osiecka, Oktawia; Wlodarczyk, Agnieszka; Kapinska-Mrowiecka, Monika; Kwitniewski, Mateusz; Majewski, Pawel; Dubin, Adam; Cichy, Joanna

2017-03-01

Eosinophils constitute an important component of helminth immunity and are not only associated with various allergies but are also linked to autoinflammatory disorders, including the skin disease psoriasis. Here we demonstrate the functional relationship between eosinophils and plasmacytoid dendritic cells (pDCs) as related to skin diseases. We previously showed that pDCs colocalize with neutrophil extracellular traps (NETs) in psoriatic skin. Here we demonstrate that eosinophils are found in psoriatic skin near neutrophils and NETs, suggesting that pDC responses can be regulated by eosinophils. Eosinophils inhibited pDC function in vitro through a mechanism that did not involve cell contact but depended on soluble factors. In pDCs stimulated by specific NET components, eosinophil-conditioned media attenuated the production of interferon α (IFNα) but did not affect the maturation of pDCs as evidenced by the unaltered expression of the costimulatory molecules CD80 and CD86. As pDCs and IFNα play a key role in autoimmune skin inflammation, these data suggest that eosinophils may influence autoinflammatory responses through their impact on the production of IFNα by pDCs.

The YvqE two-component system controls biofilm formation and acid production in Streptococcus pyogenes.

PubMed

Isaka, Masanori; Tatsuno, Ichiro; Maeyama, Jun-Ichi; Matsui, Hideyuki; Zhang, Yan; Hasegawa, Tadao

2016-07-01

In Streptococcus pyogenes, proteins involved in determining virulence are controlled by stand-alone response regulators and by two-component regulatory systems. Previous studies reported that, compared to the parental strain, the yvqE sensor knockout strain showed significantly reduced growth and lower virulence. To determine the function of YvqE, we performed biofilm analysis and pH assays on yvqE mutants, and site-directed mutagenesis of YvqE. The yvqE deletion mutant showed a slower acid production rate, indicating that YvqE regulates acid production from sugar fermentation. The mutant strain, in which the Asp(26) residue in YvqE was replaced with Asn, affected biofilm formation, suggesting that this amino acid senses hydrogen ions produced by fermentative sugar metabolism. Signals received by YvqE were directly or indirectly responsible for inducing pilus expression. This study shows that at low environmental pH, biofilm formation in S. pyogenes is mediated by YvqE and suggests that regulation of pilus expression by environmental acidification could be directly under the control of YvqE. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Different actions of endothelin-1 on chemokine production in rat cultured astrocytes: reduction of CX3CL1/fractalkine and an increase in CCL2/MCP-1 and CXCL1/CINC-1

PubMed Central

2013-01-01

Background Chemokines are involved in many pathological responses of the brain. Astrocytes produce various chemokines in brain disorders, but little is known about the factors that regulate astrocytic chemokine production. Endothelins (ETs) have been shown to regulate astrocytic functions through ETB receptors. In this study, the effects of ETs on chemokine production were examined in rat cerebral cultured astrocytes. Methods Astrocytes were prepared from the cerebra of one- to two-day-old Wistar rats and cultured in serum-containing medium. After serum-starvation for 48 hours, astrocytes were treated with ETs. Total RNA was extracted using an acid-phenol method and expression of chemokine mRNAs was determined by quantitative RT-PCR. The release of chemokines was measured by ELISA. Results Treatment of cultured astrocytes with ET-1 and Ala1,3,11,15-ET-1, an ETB agonist, increased mRNA levels of CCL2/MCP1 and CXCL1/CINC-1. In contrast, CX3CL1/fractalkine mRNA expression decreased in the presence of ET-1 and Ala1,3,11,15-ET-1. The effect of ET-1 on chemokine mRNA expression was inhibited by BQ788, an ETB antagonist. ET-1 increased CCL2 and CXCL1 release from cultured astrocytes, but decreased that of CX3CL1. The increase in CCL2 and CXCL1 expression by ET-1 was inhibited by actinomycin D, pyrrolidine dithiocarbamate, SN50, mithramycin, SB203580 and SP600125. The decrease in CX3CL1 expression by ET-1 was inhibited by cycloheximide, Ca2+ chelation and staurosporine. Conclusion These findings suggest that ETs are one of the factors regulating astrocytic chemokine production. Astrocyte-derived chemokines are involved in pathophysiological responses of neurons and microglia. Therefore, the ET-induced alterations of astrocytic chemokine production are of pathophysiological significance in damaged brains. PMID:23627909

RhMKK9, a rose MAP KINASE KINASE gene, is involved in rehydration-triggered ethylene production in rose gynoecia.

PubMed

Chen, Jiwei; Zhang, Qian; Wang, Qigang; Feng, Ming; Li, Yang; Meng, Yonglu; Zhang, Yi; Liu, Guoqin; Ma, Zhimin; Wu, Hongzhi; Gao, Junping; Ma, Nan

2017-02-23

Flower opening is an important process in the life cycle of flowering plants and is influenced by various endogenous and environmental factors. Our previous work demonstrated that rose (Rosa hybrida) flowers are highly sensitive to dehydration during flower opening and the water recovery process after dehydration induced ethylene production rapidly in flower gynoecia. In addition, this temporal- and spatial-specific ethylene production is attributed to a transient but robust activation of the rose MAP KINASE6-ACC SYNTHASE1 (RhMPK6-RhACS1) cascade in gynoecia. However, the upstream component of RhMPK6-RhACS1 is unknown, although RhMKK9 (MAP KINASE KINASE9), a rose homologue of Arabidopsis MKK9, could activate RhMPK6 in vitro. In this study, we monitored RhMKK2/4/5/9 expression, the potential upstream kinase to RhMPK6, in rose gynoecia during dehydration and rehydration. We found only RhMKK9 was rapidly and strongly induced by rehydration. Silencing of RhMKK9 significantly decreased rehydration-triggered ethylene production. Consistently, the expression of several ethylene-responsive genes was down regulated in the petals of RhMKK9-silenced flowers. Moreover, we detected the DNA methylation level in the promoter and gene body of RhMKK9 by Chop-PCR. The results showed that rehydration specifically elevated the DNA methylation level on the RhMKK9 gene body, whereas it resulted in hypomethylation in its promoter. Our results showed that RhMKK9 possibly acts as the upstream component of the RhMKK9-RhMPK6-RhACS1 cascade and is responsible for water recovery-triggered ethylene production in rose gynoecia, and epigenetic DNA methylation is involved in the regulation of RhMKK9 expression by rehydration.

Renal Protective Role of Xiexin Decoction with Multiple Active Ingredients Involves Inhibition of Inflammation through Downregulation of the Nuclear Factor-κB Pathway in Diabetic Rats

PubMed Central

Wu, Jia-sheng; Shi, Rong; Zhong, Jie; Lu, Xiong; Ma, Bing-liang; Wang, Tian-ming; Zan, Bin; Ma, Yue-ming; Cheng, Neng-neng; Qiu, Fu-rong

2013-01-01

In Chinese medicine, Xiexin decoction (XXD) has been used for the clinical treatment of diabetes for at least 1700 years. The present study was conducted to investigate the effective ingredients of XXD and their molecular mechanisms of antidiabetic nephropathy in rats. Rats with diabetes induced by high-fat diet and streptozotocin were treated with XXD extract for 12 weeks. XXD significantly improved the glucolipid metabolism disorder, attenuated albuminuria and renal pathological changes, reduced renal advanced glycation end-products, inhibited receptor for advanced glycation end-product and inflammation factors expression, suppressed renal nuclear factor-κB pathway activity, and downregulated renal transforming growth factor-β1. The concentrations of multiple components in plasma from XXD were determined by liquid chromatography and tandem mass spectrometry. Pharmacokinetic/pharmacodynamic analysis using partial least square regression revealed that 8 ingredients of XXD were responsible for renal protective effects via actions on multiple molecular targets. Our study suggests that the renal protective role of XXD with multiple effective ingredients involves inhibition of inflammation through downregulation of the nuclear factor-κB pathway, reducing renal advanced glycation end-products and receptor for advanced glycation end-product in diabetic rats. PMID:23935673

Comprehensive Proteomics Analysis of Laticifer Latex Reveals New Insights into Ethylene Stimulation of Natural Rubber Production.

PubMed

Wang, Xuchu; Wang, Dan; Sun, Yong; Yang, Qian; Chang, Lili; Wang, Limin; Meng, Xueru; Huang, Qixing; Jin, Xiang; Tong, Zheng

2015-09-08

Ethylene is a stimulant to increase natural rubber latex. After ethylene application, both fresh yield and dry matter of latex are substantially improved. Moreover, we found that ethylene improves the generation of small rubber particles. However, most genes involved in rubber biosynthesis are inhibited by exogenous ethylene. Therefore, we conducted a proteomics analysis of ethylene-stimulated rubber latex, and identified 287 abundant proteins as well as 143 ethylene responsive latex proteins (ERLPs) with mass spectrometry from the 2-DE and DIGE gels, respectively. In addition, more than 1,600 proteins, including 404 ERLPs, were identified by iTRAQ. Functional classification of ERLPs revealed that enzymes involved in post-translational modification, carbohydrate metabolism, hydrolase activity, and kinase activity were overrepresented. Some enzymes for rubber particle aggregation were inhibited to prolong latex flow, and thus finally improved latex production. Phosphoproteomics analysis identified 59 differential phosphoproteins; notably, specific isoforms of rubber elongation factor and small rubber particle protein that were phosphorylated mainly at serine residues. This post-translational modification and isoform-specific phosphorylation might be important for ethylene-stimulated latex production. These results not only deepen our understanding of the rubber latex proteome but also provide new insights into the use of ethylene to stimulate rubber latex production.

Dissociation of Innate Immune Responses in Microglia Infected with Listeria monocytogenes

PubMed Central

Frande-Cabanes, Elisabet; Fernandez-Prieto, Lorena; Calderon-Gonzalez, Ricardo; Rodríguez-Del Río, Estela; Yañez-Diaz, Sonsoles; López-Fanarraga, Monica; Alvarez-Domínguez, Carmen

2014-01-01

Microglia, the innate immune cells of the brain, plays a central role in cerebral listeriosis. Here, we present evidence that microglia control Listeria infection differently than macrophages. Infection of primary microglial cultures and murine cell lines with Listeria resulted in a dual function of the two gene expression programmes involved in early and late immune responses in macrophages. Whereas the bacterial gene hly seems responsible for both transcriptional programmes in macrophages, Listeria induces in microglia only the tumor necrosis factor (TNF)-regulated transcriptional programme. Listeria also represses in microglia the late immune response gathered in two clusters, microbial degradation, and interferon (IFN)-inducible genes. The bacterial gene actA was required in microglia to induce TNF-regulated responses and to repress the late response. Isolation of microglial phagosomes revealed a phagosomal environment unable to destroy Listeria. Microglial phagosomes were also defective in several signaling and trafficking components reported as relevant for Listeria innate immune responses. This transcriptional strategy in microglia induced high levels of TNF-α and monocyte chemotactic protein-1 and low production of other neurotoxic compounds such as nitric oxide, hydrogen peroxide, and Type I IFNs. These cytokines and toxic microglial products are also released by primary microglia, and this cytokine and chemokine cocktail display a low potential to trigger neuronal apoptosis. This overall bacterial strategy strongly suggests that microglia limit Listeria inflammation pattern exclusively through TNF-mediated responses to preserve brain integrity. GLIA 2014;62:233–246 PMID:24311463

Examining the relationship between comprehension and production processes in code-switched language

PubMed Central

Guzzardo Tamargo, Rosa E.; Valdés Kroff, Jorge R.; Dussias, Paola E.

2016-01-01

We employ code-switching (the alternation of two languages in bilingual communication) to test the hypothesis, derived from experience-based models of processing (e.g., Boland, Tanenhaus, Carlson, & Garnsey, 1989; Gennari & MacDonald, 2009), that bilinguals are sensitive to the combinatorial distributional patterns derived from production and that they use this information to guide processing during the comprehension of code-switched sentences. An analysis of spontaneous bilingual speech confirmed the existence of production asymmetries involving two auxiliary + participle phrases in Spanish–English code-switches. A subsequent eye-tracking study with two groups of bilingual code-switchers examined the consequences of the differences in distributional patterns found in the corpus study for comprehension. Participants’ comprehension costs mirrored the production patterns found in the corpus study. Findings are discussed in terms of the constraints that may be responsible for the distributional patterns in code-switching production and are situated within recent proposals of the links between production and comprehension. PMID:28670049

Examining the relationship between comprehension and production processes in code-switched language.

PubMed

Guzzardo Tamargo, Rosa E; Valdés Kroff, Jorge R; Dussias, Paola E

2016-08-01

We employ code-switching (the alternation of two languages in bilingual communication) to test the hypothesis, derived from experience-based models of processing (e.g., Boland, Tanenhaus, Carlson, & Garnsey, 1989; Gennari & MacDonald, 2009), that bilinguals are sensitive to the combinatorial distributional patterns derived from production and that they use this information to guide processing during the comprehension of code-switched sentences. An analysis of spontaneous bilingual speech confirmed the existence of production asymmetries involving two auxiliary + participle phrases in Spanish-English code-switches. A subsequent eye-tracking study with two groups of bilingual code-switchers examined the consequences of the differences in distributional patterns found in the corpus study for comprehension. Participants' comprehension costs mirrored the production patterns found in the corpus study. Findings are discussed in terms of the constraints that may be responsible for the distributional patterns in code-switching production and are situated within recent proposals of the links between production and comprehension.

Intracellular response to process optimization and impact on productivity and product aggregates for a high-titer CHO cell process.

PubMed

Handlogten, Michael W; Lee-O'Brien, Allison; Roy, Gargi; Levitskaya, Sophia V; Venkat, Raghavan; Singh, Shailendra; Ahuja, Sanjeev

2018-01-01

A key goal in process development for antibodies is to increase productivity while maintaining or improving product quality. During process development of an antibody, titers were increased from 4 to 10 g/L while simultaneously decreasing aggregates. Process development involved optimization of media and feed formulations, feed strategy, and process parameters including pH and temperature. To better understand how CHO cells respond to process changes, the changes were implemented in a stepwise manner. The first change was an optimization of the feed formulation, the second was an optimization of the medium, and the third was an optimization of process parameters. Multiple process outputs were evaluated including cell growth, osmolality, lactate production, ammonium concentration, antibody production, and aggregate levels. Additionally, detailed assessment of oxygen uptake, nutrient and amino acid consumption, extracellular and intracellular redox environment, oxidative stress, activation of the unfolded protein response (UPR) pathway, protein disulfide isomerase (PDI) expression, and heavy and light chain mRNA expression provided an in-depth understanding of the cellular response to process changes. The results demonstrate that mRNA expression and UPR activation were unaffected by process changes, and that increased PDI expression and optimized nutrient supplementation are required for higher productivity processes. Furthermore, our findings demonstrate the role of extra- and intracellular redox environment on productivity and antibody aggregation. Processes using the optimized medium, with increased concentrations of redox modifying agents, had the highest overall specific productivity, reduced aggregate levels, and helped cells better withstand the high levels of oxidative stress associated with increased productivity. Specific productivities of different processes positively correlated to average intracellular values of total glutathione. Additionally, processes with the optimized media maintained an oxidizing intracellular environment, important for correct disulfide bond pairing, which likely contributed to reduced aggregate formation. These findings shed important understanding into how cells respond to process changes and can be useful to guide future development efforts to enhance productivity and improve product quality. © 2017 Wiley Periodicals, Inc.

Annual Removal of Aboveground Plant Biomass Alters Soil Microbial Responses to Warming

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

Xue, Kai; Yuan, Mengting M.; Xie, Jianping

Clipping (i.e., harvesting aboveground plant biomass) is common in agriculture and for bioenergy production. However, microbial responses to clipping in the context of climate warming are poorly understood. We investigated the interactive effects of grassland warming and clipping on soil properties and plant and microbial communities, in particular, on microbial functional genes. Clipping alone did not change the plant biomass production, but warming and clipping combined increased the C4 peak biomass by 47% and belowground net primary production by 110%. Clipping alone and in combination with warming decreased the soil carbon input from litter by 81% and 75%, respectively. Withmore » less carbon input, the abundances of genes involved in degrading relatively recalcitrant carbon increased by 38% to 137% in response to either clipping or the combined treatment, which could weaken long-term soil carbon stability and trigger positive feedback with respect to warming. Clipping alone also increased the abundance of genes for nitrogen fixation, mineralization, and denitrification by 32% to 39%. Such potentially stimulated nitrogen fixation could help compensate for the 20% decline in soil ammonium levels caused by clipping alone and could contribute to unchanged plant biomass levels. Moreover, clipping tended to interact antagonistically with warming, especially with respect to effects on nitrogen cycling genes, demonstrating that single-factor studies cannot predict multifactorial changes. These results revealed that clipping alone or in combination with warming altered soil and plant properties as well as the abundance and structure of soil microbial functional genes. Aboveground biomass removal for biofuel production needs to be reconsidered, as the long-term soil carbon stability may be weakened. IMPORTANCE Global change involves simultaneous alterations, including those caused by climate warming and land management practices (e.g., clipping). Data on the interactive effects of warming and clipping on ecosystems remain elusive, particularly in microbial ecology. This study found that clipping alters microbial responses to warming and demonstrated the effects of antagonistic interactions between clipping and warming on microbial functional genes. Clipping alone or combined with warming enriched genes degrading relatively recalcitrant carbon, likely reflecting the decreased quantity of soil carbon input from litter, which could weaken long-term soil C stability and trigger positive warming feedback. These results have important implications in assessing and predicting the consequences of global climate change and indicate that the removal of aboveground biomass for biofuel production may need to be reconsidered.« less

Annual Removal of Aboveground Plant Biomass Alters Soil Microbial Responses to Warming

DOE PAGES

Xue, Kai; Yuan, Mengting M.; Xie, Jianping; ...

2016-09-27

Clipping (i.e., harvesting aboveground plant biomass) is common in agriculture and for bioenergy production. However, microbial responses to clipping in the context of climate warming are poorly understood. We investigated the interactive effects of grassland warming and clipping on soil properties and plant and microbial communities, in particular, on microbial functional genes. Clipping alone did not change the plant biomass production, but warming and clipping combined increased the C4 peak biomass by 47% and belowground net primary production by 110%. Clipping alone and in combination with warming decreased the soil carbon input from litter by 81% and 75%, respectively. Withmore » less carbon input, the abundances of genes involved in degrading relatively recalcitrant carbon increased by 38% to 137% in response to either clipping or the combined treatment, which could weaken long-term soil carbon stability and trigger positive feedback with respect to warming. Clipping alone also increased the abundance of genes for nitrogen fixation, mineralization, and denitrification by 32% to 39%. Such potentially stimulated nitrogen fixation could help compensate for the 20% decline in soil ammonium levels caused by clipping alone and could contribute to unchanged plant biomass levels. Moreover, clipping tended to interact antagonistically with warming, especially with respect to effects on nitrogen cycling genes, demonstrating that single-factor studies cannot predict multifactorial changes. These results revealed that clipping alone or in combination with warming altered soil and plant properties as well as the abundance and structure of soil microbial functional genes. Aboveground biomass removal for biofuel production needs to be reconsidered, as the long-term soil carbon stability may be weakened. IMPORTANCE Global change involves simultaneous alterations, including those caused by climate warming and land management practices (e.g., clipping). Data on the interactive effects of warming and clipping on ecosystems remain elusive, particularly in microbial ecology. This study found that clipping alters microbial responses to warming and demonstrated the effects of antagonistic interactions between clipping and warming on microbial functional genes. Clipping alone or combined with warming enriched genes degrading relatively recalcitrant carbon, likely reflecting the decreased quantity of soil carbon input from litter, which could weaken long-term soil C stability and trigger positive warming feedback. These results have important implications in assessing and predicting the consequences of global climate change and indicate that the removal of aboveground biomass for biofuel production may need to be reconsidered.« less

Skin blood flow responses to the iontophoresis of acetylcholine and sodium nitroprusside in man: possible mechanisms.

PubMed

Morris, S J; Shore, A C

1996-10-15

1. The mechanisms involved in the human skin blood flow responses to iontophoretic application of acetylcholine (ACH; delivered using an anodal charge) or sodium nitroprusside (SNP; administered with a cathodal charge) are unclear. The aims of this study were to investigate possible contributions of prostaglandin production to the increase in skin blood flow induced following the iontophoresis of ACh and to investigate possible contributions from local sensory nerves to the perfusion responses induced by ACh, SNP and their vehicles. 2. The contribution of prostaglandins to the ACh response was determined in a randomized double-blind study of eight healthy subjects, who were studied on two occasions. Basal responses to ACh were measured before the oral administration of 600 mg soluble aspirin in diluted orange juice (1 occasion or orange juice (1 occasion) and again 30 min after the drink. The contribution of local sensory nerve activation to the responses to ACh and ACh vehicle (8 subjects) and to SNP and SNP vehicle (7 subjects) was assessed. EMLA (5%) (a eutectic mixture of lignocaine and prilocaine) and placebo cream were applied to two separate areas on the forearm in a double-blind randomized manner 2 h before drug responses were measured. In all studies the skin microcirculation responses to iontophoretically applied drug vehicle (1 site) and drug (2 sites) were recorded by laser Doppler perfusion imaging. 3. The increase in forearm skin perfusion (P < 0.001) in response to the iontophoresis of ACh minus the response to ACh vehicle was not significantly different following placebo or aspirin administration. The increase in forearm skin red blood cell flux (P < 0.001) in response to the iontophoresis of ACh minus the response to ACh vehicle was not significantly different at the placebo-compared with the EMLA-treated site. THe small increase in perfusion (P < 0.001) in response to the iontophoresis of ACh vehicle was significantly inhibited at the EMLA-compared with the placebo-treated site (P < 0.05). The marked increase in perfusion (P < 0.001) in response to the iontophoresis of SNP vehicle was significantly inhibited at the EMLA-compared with the placebo-treated site (P < 0.01). 4. These data suggest that in healthy volunteers: (1) mechanisms other than prostaglandin production and local sensory nerve activation may be involved in the increase in skin perfusion observed following the iontophoretic application of ACh; and (2) stimulation of local sensory nerves may be responsible for the increase in tissue perfusion observed following the iontophoretic application of either ACh vehicle or SNP vehicle.

Social responsibility and research ethics in community-driven studies of industrialized hog production.

PubMed Central

Wing, Steve

2002-01-01

Environmental health research can document exposures and health effects that result from inequitable relationships between communities of low income or people of color and the institutions that derive benefits (profits, federal and state funding or services, avoidance of wastes) from activities and policies that burden these communities. Researchers, most of whom work in relatively privileged institutions, are placed in situations of conflicting loyalties if they conduct research in collaboration with, or on behalf of, communities burdened by environmental injustices. These conflicts can threaten the self-interest of researchers and may raise social and ethical issues that do not typically arise in research projects that respond to the agendas of institutions. This article describes how we addressed issues of research ethics and social responsibility in environmental health research on industrialized hog production in North Carolina. Researchers and institutional review boards are not well prepared to address ethical issues when interests of entire communities, as well as individual research participants, are involved. Community-driven research partnerships can help address problems in research ethics and can enhance the social responsibility of researchers and their institutions. PMID:12003746

Food for thought or thought for food?--a stakeholder dialogue around the role of the snacking industry in addressing the obesity epidemic.

PubMed

Astrup, A; Bovy, M W L; Nackenhorst, K; Popova, A E

2006-08-01

The current obesity epidemic is generally considered multi-causal. Certain foods, including snacks such as potato chips, and their marketing are often highlighted as needing particular attention. This forces potato chip producers to take position on their role and responsibility. Based on expert interviews and a literature review, a systems analysis approach is presented that distinguishes between basic physiology, self-control and what we call jam transmitters, signals and pressures from the environment that hinder or frustrate self-control. Examples of the latter are commercial push and seduction, obesogenic cultures, obesogenic physical environment, socioeconomic factors, genes, hormones and instincts. Solution of the epidemic demands an approach that involves all factors and all related actors. As for the snacking industry, the comprehensive responses are: to introduce specific diet products; to improve the nutritional quality of its products; the latter combined with supporting and engaging in healthy lifestyle marketing; to practice responsible targeting of marketing; and to limit the promotion of unhealthy consumption patterns.

FudC, a protein primarily responsible for furfural detoxification in Corynebacterium glutamicum.

PubMed

Tsuge, Yota; Kudou, Motonori; Kawaguchi, Hideo; Ishii, Jun; Hasunuma, Tomohisa; Kondo, Akihiko

2016-03-01

Lignocellulosic hydrolysates contain compounds that inhibit microbial growth and fermentation, thereby decreasing the productivity of biofuel and biochemical production. In particular, the heterocyclic aldehyde furfural is one of the most toxic compounds found in these hydrolysates. We previously demonstrated that Corynebacterium glutamicum converts furfural into the less toxic compounds furfuryl alcohol and 2-furoic acid. To date, however, the genes involved in these oxidation and reduction reactions have not been identified in the C. glutamicum genome. Here, we show that Cgl0331 (designated FudC) is mainly responsible for the reduction of furfural into furfuryl alcohol in C. glutamicum. Deletion of the gene encoding FudC markedly diminished the in vivo reduction of furfural to furfuryl alcohol. Purified His-tagged FudC protein from Escherichia coli was also shown to convert furfural into furfuryl alcohol in an in vitro reaction utilizing NADPH, but not NADH, as a cofactor. Kinetic measurements demonstrated that FudC has a high affinity for furfural but has a narrow substrate range for other aldehydes compared to the protein responsible for furfural reduction in E. coli.

Lanthanum Element Induced Imbalance of Mineral Nutrients, HSP 70 Production and DNA-Protein Crosslink, Leading to Hormetic Response of Cell Cycle Progression in Root Tips of Vicia faba L. seedlings.

PubMed

Wang, Chengrun; Shi, Cuie; Liu, Ling; Wang, Chen; Qiao, Wei; Gu, Zhimang; Wang, Xiaorong

2012-01-01

The effects and mechanisms of rare earth elements on plant growth have not been extensively characterized. In the current study, Vicia faba L. seedlings were cultivated in lanthanum (La)-containing solutions for 10 days to investigate the possible effects and mechanisms of La on cell proliferation and root lengthening in roots. The results showed that increasing La levels resulted in abnormal calcium (Ca), Ferrum (Fe) or Potassium (K) contents in the roots. Flow cytometry analysis revealed G1/S and S/G2 arrests in response to La treatments in the root tips. Heat shock protein 70 (HSP 70) production showed a U-shaped dose response to increasing La levels. Consistent with its role in cell cycle regulation, HSP 70 fluctuated in parallel with the S-phase ratios and proliferation index. Furthermore, DNA-protein crosslinks (DPCs) enhanced at higher La concentrations, perhaps involved in blocking cell progression. Taken together, these data provide important insights into the hormetic effects and mechanisms of REE(s) on plant cell proliferation and growth.

RIOK3 Is an Adaptor Protein Required for IRF3-Mediated Antiviral Type I Interferon Production

PubMed Central

Feng, Jun; De Jesus, Paul D.; Su, Victoria; Han, Stephanie; Gong, Danyang; Wu, Nicholas C.; Tian, Yuan; Li, Xudong; Wu, Ting-Ting; Chanda, Sumit K.

2014-01-01

ABSTRACT Detection of cytosolic nucleic acids by pattern recognition receptors leads to the induction of type I interferons (IFNs) and elicits the innate immune response. We report here the identification of RIOK3 as a novel adaptor protein that is essential for the cytosolic nucleic acid-induced type I IFN production and for the antiviral response to gammaherpesvirus through two independent kinome-wide RNA interference screens. RIOK3 knockdown blocks both cytosolic double-stranded B-form DNA and double-stranded RNA-induced IRF3 activation and IFN-β production. In contrast, the overexpression of RIOK3 activates IRF3 and induces IFN-β. RIOK3 functions downstream of TBK1 and upstream of IRF3 activation. Furthermore, RIOK3 physically interacts with both IRF3 and TBK1 and is necessary for the interaction between TBK1 and IRF3. In addition, global transcriptome analysis shows that the expression of many gene involved antiviral responses is dependent on RIOK3. Thus, knockdown of RIOK3 inhibits cellular antiviral responses against both DNA and RNA viruses (herpesvirus and influenza A virus). Our data suggest that RIOK3 plays a critical role in the antiviral type I IFN pathway by bridging TBK1 and IRF3. IMPORTANCE The innate immune response, such as the production of type I interferons, acts as the first line of defense, limiting infectious pathogens directly and shaping the adaptive immune response. In this study, we identified RIOK3 as a novel regulator of the antiviral type I interferon pathway. Specifically, we found that RIOK3 physically interacts with TBK1 and IRF3 and bridges the functions between TBK1 and IRF3 in the activation of type I interferon pathway. The identification of a cellular kinase that plays a role the type I interferon pathway adds another level of complexity in the regulation of innate immunity and will have implications for developing novel strategies to combat viral infection. PMID:24807708

Transforming growth factor beta 1 increases collagen content, and stimulates procollagen I and tissue inhibitor of metalloproteinase-1 production of dental pulp cells: Role of MEK/ERK and activin receptor-like kinase-5/Smad signaling.

PubMed

Lin, Po-Shuen; Chang, Hsiao-Hua; Yeh, Chien-Yang; Chang, Mei-Chi; Chan, Chiu-Po; Kuo, Han-Yueh; Liu, Hsin-Cheng; Liao, Wan-Chuen; Jeng, Po-Yuan; Yeung, Sin-Yuet; Jeng, Jiiang-Huei

2017-05-01

In order to clarify the role of transforming growth factor beta 1 (TGF-β1) in pulp repair/regeneration responses, we investigated the differential signaling pathways responsible for the effects of TGF-β1 on collagen turnover, matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of metalloproteinase-1 (TIMP-1) production in human dental pulp cells. Pulp cells were exposed to TGF-β1 with/without pretreatment and coincubation by 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenyl mercapto)butadiene (U0126; a mitogen-activated protein kinase kinase [MEK]/extracellular signal-regulated kinase [ERK] inhibitor) and 4-(5-benzol[1,3]dioxol-5-yl-4-pyrldin-2-yl-1H- imidazol-2-yl)-benzamide hydrate (SB431542; an activin receptor-like kinase-5/Smad signaling inhibitor). Sircol collagen assay was used to measure cellular collagen content. Culture medium procollagen I, TIMP-1, and MMP-3 levels were determined by enzyme-linked immunosorbent assay. TGF-β1 increased the collagen content, procollagen I, and TIMP-1 production, but slightly decreased MMP-3 production of pulp cells. SB431542 and U0126 prevented the TGF-β1-induced increase of collagen content and TIMP-1 production of dental pulp cells. These results indicate that TGF-β1 may be involved in the healing/regeneration processes of dental pulp in response to injury by stimulation of collagen and TIMP-1 production. These events are associated with activin receptor-like kinase-5/Smad2/3 and MEK/ERK signaling. Copyright © 2016. Published by Elsevier B.V.

Toxicology and cellular effect of manufactured nanomaterials

DOEpatents

Chen, Fanqing

2014-07-22

The increasing use of nanotechnology in consumer products and medical applications underlies the importance of understanding its potential toxic effects to people and the environment. Herein are described methods and assays to predict and evaluate the cellular effects of nanomaterial exposure. Exposing cells to nanomaterials at cytotoxic doses induces cell cycle arrest and increases apoptosis/necrosis, activates genes involved in cellular transport, metabolism, cell cycle regulation, and stress response. Certain nanomaterials induce genes indicative of a strong immune and inflammatory response within skin fibroblasts. Furthermore, the described multiwall carbon nanoonions (MWCNOs) can be used as a therapeutic in the treatment of cancer due to its cytotoxicity.

The multifaceted biology of plasmacytoid dendritic cells

PubMed Central

Swiecki, Melissa; Colonna, Marco

2015-01-01

Plasmacytoid dendritic cells (pDCs) are a unique dendritic cell subset that specializes in the production of type I interferons (IFNs). pDCs promote antiviral immune responses and have been implicated in the pathogenesis of autoimmune diseases characterized by a type I IFN signature. However, pDCs can also induce tolerogenic immune responses. Here, we review recent progress from the field of pDC biology, focusing on: the molecular mechanisms that regulate pDC development and functions; the pathways involved in their sensing of pathogens and endogenous nucleic acids; the function of pDCs at mucosal sites; and their roles in infections, autoimmunity and cancer. PMID:26160613

Diagnosis and Management of Subacute Ruminal Acidosis in Dairy Herds.

PubMed

Oetzel, Garrett R

2017-11-01

Subacute ruminal acidosis (SARA) is a common problem in lactating dairy cows that causes chronic health problems, impairs feed efficiency, and increases the environmental impact of milk production. Low ruminal pH appears to be the main instigator of the pathophysiology of SARA, although other metabolites produced in the rumen may be involved. Inflammatory responses to SARA are variable but important determinants of a cow's response to SARA. SARA can be diagnosed at the herd level by integrating information about clinical signs and on-farm measures of ruminal pH. Prevention of SARA requires excellent feeding management and proper diet formulation. Copyright © 2017 Elsevier Inc. All rights reserved.

A surgeons' guide to renal transplant immunopathology, immunology, and immunosuppression.

PubMed

Gaber, Lillian W; Knight, Richard J; Patel, Samir J

2013-12-01

The response to allografting involves adaptive and innate immune mechanisms. In the adaptive system, activated T cells differentiate to cytotoxic effectors that attack the graft and trigger B cells to differentiation to plasma cells that produce anti-HLA antibodies. The innate immune system recognizes antigens in a non-specific manner and recruits immune cells to the graft through the productions of chemotactic factors, and activation of cytokines and the complement cascade. In the kidney the tubules and the endothelium are the targets of the rejection response. Immune suppression is effective in modulating the adaptive immune system effect on graft histology. Copyright © 2013 Elsevier Inc. All rights reserved.

Assessment of burning characteristics of aircraft interior materials

NASA Technical Reports Server (NTRS)

Grand, A. F.; Valys, A. J.

1981-01-01

The performance of a series of seat cushion design constructions was compared based on their heat and smoke release characteristics. Tests were conducted in a room size calorimeter instrumented for measuring weight loss, rate of heat release, smoke and volatile decomposition products and the cumulative energy release. Baseline data were obtained from burn tests conducted on commercial airline salvage sets as a comparison with more advanced seat designs. A toxicological assessment of smoke and fire gases involved the exposure of test animals and their biological responses ascertained. Relative toxicological hazards of the combustion gases are discussed based on the animal response studies and the analysis of the combustion gases.

Molecular Mechanisms for Herpes Simplex Virus Type 1 Pathogenesis in Alzheimer’s Disease

PubMed Central

Harris, Steven A.; Harris, Elizabeth A.

2018-01-01

This review focuses on research in the areas of epidemiology, neuropathology, molecular biology and genetics that implicates herpes simplex virus type 1 (HSV-1) as a causative agent in the pathogenesis of sporadic Alzheimer’s disease (AD). Molecular mechanisms whereby HSV-1 induces AD-related pathophysiology and pathology, including neuronal production and accumulation of amyloid beta (Aβ), hyperphosphorylation of tau proteins, dysregulation of calcium homeostasis, and impaired autophagy, are discussed. HSV-1 causes additional AD pathologies through mechanisms that promote neuroinflammation, oxidative stress, mitochondrial damage, synaptic dysfunction, and neuronal apoptosis. The AD susceptibility genes apolipoprotein E (APOE), phosphatidylinositol binding clathrin assembly protein (PICALM), complement receptor 1 (CR1) and clusterin (CLU) are involved in the HSV lifecycle. Polymorphisms in these genes may affect brain susceptibility to HSV-1 infection. APOE, for example, influences susceptibility to certain viral infections, HSV-1 viral load in the brain, and the innate immune response. The AD susceptibility gene cholesterol 25-hydroxylase (CH25H) is upregulated in the AD brain and is involved in the antiviral immune response. HSV-1 interacts with additional genes to affect cognition-related pathways and key enzymes involved in Aβ production, Aβ clearance, and hyperphosphorylation of tau proteins. Aβ itself functions as an antimicrobial peptide (AMP) against various pathogens including HSV-1. Evidence is presented supporting the hypothesis that Aβ is produced as an AMP in response to HSV-1 and other brain infections, leading to Aβ deposition and plaque formation in AD. Epidemiologic studies associating HSV-1 infection with AD and cognitive impairment are discussed. Studies are reviewed supporting subclinical chronic reactivation of latent HSV-1 in the brain as significant in the pathogenesis of AD. Finally, the rationale for and importance of clinical trials treating HSV-1-infected MCI and AD patients with antiviral medication is discussed. PMID:29559905