TGMI: an efficient algorithm for identifying pathway regulators through evaluation of triple-gene mutual interaction

PubMed Central

Gunasekara, Chathura; Zhang, Kui; Deng, Wenping; Brown, Laura

2018-01-01

Abstract Despite their important roles, the regulators for most metabolic pathways and biological processes remain elusive. Presently, the methods for identifying metabolic pathway and biological process regulators are intensively sought after. We developed a novel algorithm called triple-gene mutual interaction (TGMI) for identifying these regulators using high-throughput gene expression data. It first calculated the regulatory interactions among triple gene blocks (two pathway genes and one transcription factor (TF)), using conditional mutual information, and then identifies significantly interacted triple genes using a newly identified novel mutual interaction measure (MIM), which was substantiated to reflect strengths of regulatory interactions within each triple gene block. The TGMI calculated the MIM for each triple gene block and then examined its statistical significance using bootstrap. Finally, the frequencies of all TFs present in all significantly interacted triple gene blocks were calculated and ranked. We showed that the TFs with higher frequencies were usually genuine pathway regulators upon evaluating multiple pathways in plants, animals and yeast. Comparison of TGMI with several other algorithms demonstrated its higher accuracy. Therefore, TGMI will be a valuable tool that can help biologists to identify regulators of metabolic pathways and biological processes from the exploded high-throughput gene expression data in public repositories. PMID:29579312

Exploring Self-regulation of More or Less Expert College-Age Video Game Players: A Sequential Explanatory Design.

PubMed

Yilmaz Soylu, Meryem; Bruning, Roger H

2016-01-01

This study examined differences in self-regulation among college-age expert, moderately expert, and non-expert video game players in playing video games for fun. Winne's model of self-regulation (Winne, 2001) guided the study. The main assumption of this study was that expert video game players used more processes of self-regulation than the less-expert players. We surveyed 143 college students about their game playing frequency, habits, and use of self-regulation. Data analysis indicated that while playing recreational video games, expert gamers self-regulated more than moderately expert and non-expert players and moderately expert players used more processes of self-regulation than non-experts. Semi-structured interviews also were conducted with selected participants at each of the expertise levels. Qualitative follow-up analyses revealed five themes: (1) characteristics of expert video gamers, (2) conditions for playing a video game, (3) figuring out a game, (4) how gamers act and, (5) game context. Overall, findings indicated that playing a video game is a highly self-regulated activity and that becoming an expert video game player mobilizes multiple sets of self-regulation related skills and processes. These findings are seen as promising for educators desiring to encourage student self-regulation, because they indicate the possibility of supporting students via recreational video games by recognizing that their play includes processes of self-regulation.

Exploring Self-regulation of More or Less Expert College-Age Video Game Players: A Sequential Explanatory Design

PubMed Central

Yilmaz Soylu, Meryem; Bruning, Roger H.

2016-01-01

This study examined differences in self-regulation among college-age expert, moderately expert, and non-expert video game players in playing video games for fun. Winne's model of self-regulation (Winne, 2001) guided the study. The main assumption of this study was that expert video game players used more processes of self-regulation than the less-expert players. We surveyed 143 college students about their game playing frequency, habits, and use of self-regulation. Data analysis indicated that while playing recreational video games, expert gamers self-regulated more than moderately expert and non-expert players and moderately expert players used more processes of self-regulation than non-experts. Semi-structured interviews also were conducted with selected participants at each of the expertise levels. Qualitative follow-up analyses revealed five themes: (1) characteristics of expert video gamers, (2) conditions for playing a video game, (3) figuring out a game, (4) how gamers act and, (5) game context. Overall, findings indicated that playing a video game is a highly self-regulated activity and that becoming an expert video game player mobilizes multiple sets of self-regulation related skills and processes. These findings are seen as promising for educators desiring to encourage student self-regulation, because they indicate the possibility of supporting students via recreational video games by recognizing that their play includes processes of self-regulation. PMID:27729881

IRAS: High-Throughput Identification of Novel Alternative Splicing Regulators.

PubMed

Zheng, S

2016-01-01

Alternative splicing is a fundamental regulatory process of gene expression. Defects in alternative splicing can lead to various diseases, and modification of disease-causing splicing events presents great therapeutic promise. Splicing outcome is commonly affected by extracellular stimuli and signaling cascades that converge on RNA-binding splicing regulators. These trans-acting factors recognize cis-elements in pre-mRNA transcripts to affect spliceosome assembly and splice site choices. Identification of these splicing regulators and/or upstream modulators has been difficult and traditionally done by piecemeal. High-throughput screening strategies to find multiple regulators of exon splicing have great potential to accelerate the discovery process, but typically confront low sensitivity and low specificity of screening assays. Here we describe a unique screening strategy, IRAS (identifying regulators of alternative splicing), using a pair of dual-output minigene reporters to allow for sensitive detection of exon splicing changes. Each dual-output reporter produces green fluorescent protein (GFP) and red fluorescent protein (RFP) fluorescent signals to assay the two spliced isoforms exclusively. The two complementary minigene reporters alter GFP/RFP output ratios in the opposite direction in response to splicing change. Applying IRAS in cell-based high-throughput screens allows sensitive and specific identification of splicing regulators and modulators for any alternative exons of interest. In comparison to previous high-throughput screening methods, IRAS substantially enhances the specificity of the screening assay. This strategy significantly eliminates false positives without sacrificing sensitive identification of true regulators of splicing. © 2016 Elsevier Inc. All rights reserved.

Working memory regulates trait anxiety-related threat processing biases.

PubMed

Booth, Robert W; Mackintosh, Bundy; Sharma, Dinkar

2017-06-01

High trait anxious individuals tend to show biased processing of threat. Correlational evidence suggests that executive control could be used to regulate such threat-processing. On this basis, we hypothesized that trait anxiety-related cognitive biases regarding threat should be exaggerated when executive control is experimentally impaired by loading working memory. In Study 1, 68 undergraduates read ambiguous vignettes under high and low working memory load; later, their interpretations of these vignettes were assessed via a recognition test. Trait anxiety predicted biased interpretation of social threat vignettes under high working memory load, but not under low working memory load. In Study 2, 53 undergraduates completed a dot probe task with fear-conditioned Japanese characters serving as threat stimuli. Trait anxiety predicted attentional bias to the threat stimuli but, again, this only occurred under high working memory load. Interestingly however, actual eye movements toward the threat stimuli were only associated with state anxiety, and this was not moderated by working memory load, suggesting that executive control regulates biased threat-processing downstream of initial input processes such as orienting. These results suggest that cognitive loads can exacerbate trait anxiety-related cognitive biases, and therefore represent a useful tool for assessing cognitive biases in future research. More importantly, since biased threat-processing has been implicated in the etiology and maintenance of anxiety, poor executive control may be a risk factor for anxiety disorders. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Proportional integral derivative, modeling and ways of stabilization for the spark plasma sintering process

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

Manière, Charles; Lee, Geuntak; Olevsky, Eugene A.

The stability of the proportional–integral–derivative (PID) control of temperature in the spark plasma sintering (SPS) process is investigated. The PID regulations of this process are tested for different SPS tooling dimensions, physical parameters conditions, and areas of temperature control. It is shown that the PID regulation quality strongly depends on the heating time lag between the area of heat generation and the area of the temperature control. Tooling temperature rate maps are studied to reveal potential areas for highly efficient PID control. The convergence of the model and experiment indicates that even with non-optimal initial PID coefficients, it is possiblemore » to reduce the temperature regulation inaccuracy to less than 4 K by positioning the temperature control location in highly responsive areas revealed by the finite-element calculations of the temperature spatial distribution.« less

Proportional integral derivative, modeling and ways of stabilization for the spark plasma sintering process

DOE PAGES

Manière, Charles; Lee, Geuntak; Olevsky, Eugene A.

2017-04-21

The stability of the proportional–integral–derivative (PID) control of temperature in the spark plasma sintering (SPS) process is investigated. The PID regulations of this process are tested for different SPS tooling dimensions, physical parameters conditions, and areas of temperature control. It is shown that the PID regulation quality strongly depends on the heating time lag between the area of heat generation and the area of the temperature control. Tooling temperature rate maps are studied to reveal potential areas for highly efficient PID control. The convergence of the model and experiment indicates that even with non-optimal initial PID coefficients, it is possiblemore » to reduce the temperature regulation inaccuracy to less than 4 K by positioning the temperature control location in highly responsive areas revealed by the finite-element calculations of the temperature spatial distribution.« less

The Perceptions of Temporal Path Analysis of Learners' Self-Regulation on Learning Stress and Social Relationships in Junior High School

ERIC Educational Resources Information Center

Chang, Hsiu-Ju

2016-01-01

This research focus on the temporal path analysis of learning stress, test anxiety, peer stress (classmate relatedness), teacher relatedness, autonomy, and self-regulative performance in junior high school. Owing to the processes of self-determination always combines several negotiations with the interactive perceptions of personal experiences and…

Patterns in Clinical Students' Self-Regulated Learning Behavior: A Q-Methodology Study

ERIC Educational Resources Information Center

Berkhout, Joris J.; Teunissen, Pim W.; Helmich, Esther; van Exel, Job; van der Vleuten, Cees P.; Jaarsma, Debbie A.

2017-01-01

Students feel insufficiently supported in clinical environments to engage in active learning and achieve a high level of self-regulation. As a result clinical learning is highly demanding for students. Because of large differences between students, supervisors may not know how to support them in their learning process. We explored patterns in…

Longitudinal Study of Self-Regulation, Positive Parenting, and Adjustment Problems among Physically Abused Children

ERIC Educational Resources Information Center

Kim-Spoon, Jungmeen.; Haskett, Mary E.; Longo, Gregory S.; Nice, Rachel.

2012-01-01

Objective: Research using normative and high-risk samples indicates a significant link between problems with self-regulation and child maladjustment. Nevertheless, little is known about the processes that may modify the link between self-regulation and maladjustment. This longitudinal study examined the joint contributions of child self-regulation…

Emotional intensity influences pre-implementation and implementation of distraction and reappraisal

PubMed Central

Shafir, Roni; Schwartz, Naama; Blechert, Jens

2015-01-01

Although emotional intensity powerfully challenges regulatory strategies, its influence remains largely unexplored in affective-neuroscience. Accordingly, the present study addressed the moderating role of emotional intensity in two regulatory stages—implementation (during regulation) and pre-implementation (prior to regulation), of two major cognitive regulatory strategies—distraction and reappraisal. According to our framework, because distraction implementation involves early attentional disengagement from emotional information before it gathers force, in high-intensity it should be more effective in the short-term, relative to reappraisal, which modulates emotional processing only at a late semantic meaning phase. Supporting findings showed that in high (but not low) intensity, distraction implementation resulted in stronger modulation of negative experience, reduced neural emotional processing (centro-parietal late positive potential, LPP), with suggestive evidence for less cognitive effort (frontal-LPP), relative to reappraisal. Related pre-implementation findings confirmed that anticipating regulation of high-intensity stimuli resulted in distraction (over reappraisal) preference. In contrast, anticipating regulation of low-intensity stimuli resulted in reappraisal (over distraction) preference, which is most beneficial for long-term adaptation. Furthermore, anticipating cognitively demanding regulation, either in cases of regulating counter to these preferences or via the more effortful strategy of reappraisal, enhanced neural attentional resource allocation (Stimulus Preceding Negativity). Broad implications are discussed. PMID:25700568

Comparative transcriptome analysis reveals a global insight into molecular processes regulating citrate accumulation in sweet orange (Citrus sinensis).

PubMed

Lu, Xiaopeng; Cao, Xiongjun; Li, Feifei; Li, Jing; Xiong, Jiang; Long, Guiyou; Cao, Shangyin; Xie, Shenxi

2016-12-01

Citrate, the predominant organic acid in citrus, determines the taste of these fruits. However, little is known about the synergic molecular processes regulating citrate accumulation. Using 'Dahongtiancheng' (Citrus sinensis) and 'Bingtangcheng' (C. sinensis) with significant difference in citrate, the objectives of this study were to understand the global mechanisms of high-citrate accumulation in sweet orange. 'Dahongtiancheng' and 'Bingtangcheng' exhibit significantly different patterns in citrate accumulation throughout fruit development, with the largest differences observed at 50-70 days after full bloom (DAFB). Comparative transcriptome profiling was performed for the endocarps of both cultivars at 50 and 70 DAFB. Over 34.5 million clean reads per library were successfully mapped to the reference database and 670-2630 differentially expressed genes (DEGs) were found in four libraries. Among the genes, five transcription factors were ascertained to be the candidates regulating citrate accumulation. Functional assignments of the DEGs indicated that photosynthesis, the citrate cycle and amino acid metabolism were significantly altered in 'Dahongtiancheng'. Physiological and molecular analyses suggested that high photosynthetic efficiency and partial impairment of citrate catabolism were crucial for the high-citrate trait, and amino acid biosynthesis was one of the important directions for citrate flux. The results reveal a global insight into the gene expression changes in a high-citrate compared with a low-citrate sweet orange. High accumulating efficiency and impaired degradation of citrate may be associated with the high-citrate trait of 'Dahongtiancheng'. Findings in this study increase understanding of the molecular processes regulating citrate accumulation in sweet orange. © 2016 Scandinavian Plant Physiology Society.

Examining the effect of down regulation under high [CO2] on the growth of soybean assimilating a semi process-based model and FACE data

NASA Astrophysics Data System (ADS)

Sakurai, G.; Iizumi, T.; Yokozawa, M.

2011-12-01

The actual impact of elevated [CO2] with the interaction of the other climatic factors on the crop growth is still debated. In many process-based crop models, the response of photosynthesis per single leaf to environmental factors is basically described using the biochemical model of Farquhar et al. (1980). However, the decline in photosynthetic enhancement known as down regulation has not been taken into account. On the other hand, the mechanisms causing photosynthetic down regulation is still unknown, which makes it difficult to include the effect of down regulation into process-based crop models. The current results of Free-air CO2 enrichment (FACE) experiments have reported the effect of down regulation under actual environments. One of the effective approaches to involve these results into future crop yield prediction is developing a semi process-based crop growth model, which includes the effect of photosynthetic down regulation as a statistical model, and assimilating the data obtained in FACE experiments. In this study, we statistically estimated the parameters of a semi process-based model for soybean growth ('SPM-soybean') using a hierarchical Baysian method with the FACE data on soybeans (Morgan et al. 2005). We also evaluated the effect of down regulation on the soybean yield in future climatic conditions. The model selection analysis showed that the effective correction to the overestimation of the Farquhar's biochemical C3 model was to reduce the maximum rate of carboxylation (Vcmax) under elevated [CO2]. However, interestingly, the difference in the estimated final crop yields between the corrected model and the non-corrected model was very slight (Fig.1a) for future projection under climate change scenario (Miroc-ESM). This was due to that the reduction in Vcmax also brought about the reduction of the base dark respiration rate of leaves. Because the dark respiration rate exponentially increases with temperature, the slight difference in base respiration rate becomes a large difference under high temperature under the future climate scenarios. In other words, if the temperature rise is very small or zero under elevated [CO2] condition, the effect of down regulation significantly appears (Fig.1b). This result suggest that further experimental data that considering high CO2 effect and high temperature effect in field conditions should be important and elaborate the model projection of the future crop yield through data assimilation method.

Why People with More Emotion Regulation Difficulties Made a More Deontological Judgment: The Role of Deontological Inclinations

PubMed Central

Zhang, Lisong; Li, Zhongquan; Wu, Xiaoyuan; Zhang, Ziyuan

2017-01-01

Previous studies have demonstrated the key role of emotion in moral judgment, and explored the relationship between emotion regulation and moral judgment. The present study investigated the influence of individual differences in emotion regulation difficulties on moral judgment. Study 1 examined whether individuals with high emotion regulation difficulties made a more deontological judgment. Study 2 explored the underlying mechanism using a process-dissociation approach, examining whether deontological inclinations and utilitarian inclinations separately or jointly accounted for the association. The results indicated that individuals with high emotion regulation difficulties rated the utilitarian actions less morally appropriate, and one’s deontological inclinations mediated the association between emotion regulation difficulties and moral judgment. PMID:29234299

The effect of dietary fat intake on hepatic gene expression in LG/J AND SM/J mice

PubMed Central

2014-01-01

Background The liver plays a major role in regulating metabolic homeostasis and is vital for nutrient metabolism. Identifying the genetic factors regulating these processes could lead to a greater understanding of how liver function responds to a high-fat diet and how that response may influence susceptibilities to obesity and metabolic syndrome. In this study we examine differences in hepatic gene expression between the LG/J and SM/J inbred mouse strains and how gene expression in these strains is affected by high-fat diet. LG/J and SM/J are known to differ in their responses to a high-fat diet for a variety of obesity- and diabetes-related traits, with the SM/J strain exhibiting a stronger phenotypic response to diet. Results Dietary intake had a significant effect on gene expression in both inbred lines. Genes up-regulated by a high-fat diet were involved in biological processes such as lipid and carbohydrate metabolism; protein and amino acid metabolic processes were down regulated on a high-fat diet. A total of 259 unique transcripts exhibited a significant diet-by-strain interaction. These genes tended to be associated with immune function. In addition, genes involved in biochemical processes related to non-alcoholic fatty liver disease (NAFLD) manifested different responses to diet between the two strains. For most of these genes, SM/J had a stronger response to the high-fat diet than LG/J. Conclusions These data show that dietary fat impacts gene expression levels in SM/J relative to LG/J, with SM/J exhibiting a stronger response. This supports previous data showing that SM/J has a stronger phenotypic response to high-fat diet. Based upon these findings, we suggest that SM/J and its cross with the LG/J strain provide a good model for examining non-alcoholic fatty liver disease and its role in metabolic syndrome. PMID:24499025

Acute stress alters transcript expression pattern and reduces processing of proBDNF to mature BDNF in Dicentrarchus labrax

PubMed Central

2010-01-01

Background Stress involves alterations of brain functioning that may precipitate to mood disorders. The neurotrophin Brain Derived Neurotrophic Factor (BDNF) has recently been involved in stress-induced adaptation. BDNF is a key regulator of neuronal plasticity and adaptive processes. Regulation of BDNF is complex and may reflect not only stress-specific mechanisms but also hormonal and emotional responses. For this reason we used, as an animal model of stress, a fish whose brain organization is very similar to that of higher vertebrates, but is generally considered free of emotional reactions. Results We provide a comprehensive characterization of BDNF gene in the Dicentrarchus labrax and its transcriptional, translational and post-translational regulation following acute stress. While total BDNF mRNA levels are unchanged, BDNF transcripts 1c and 1d resulted down regulated after acute stress. Acute stress induces also a significant increase in proBDNF levels and reduction in mature BDNF suggesting altered regulation of proBDNF proteolytic processing. Notably, we provide here the first evidence that fishes possess a simplified proteolytic regulation of BDNF since the pro28Kda form, generated by the SKI-1 protease in mammals, is absent in fishes because the cleavage site has first emerged in reptilians. Finally, we show that the proBDNF/totBDNF ratio is a highly predictive novel quantitative biomarker to detect stress in fishes with sensitivity = 100%, specificity = 87%, and Negative Predictive Value = 100%. Conclusion The high predictivity of proBDNF/totBDNF ratio for stress in lower vertebrates indicates that processing of BDNF is a central mechanism in adaptation to stress and predicts that a similar regulation of pro/mature BDNF has likely been conserved throughout evolution of vertebrates from fish to man. PMID:20074340

Acute stress alters transcript expression pattern and reduces processing of proBDNF to mature BDNF in Dicentrarchus labrax.

PubMed

Tognoli, Chiara; Rossi, Federica; Di Cola, Francesco; Baj, Gabriele; Tongiorgi, Enrico; Terova, Genciana; Saroglia, Marco; Bernardini, Giovanni; Gornati, Rosalba

2010-01-14

Stress involves alterations of brain functioning that may precipitate to mood disorders. The neurotrophin Brain Derived Neurotrophic Factor (BDNF) has recently been involved in stress-induced adaptation. BDNF is a key regulator of neuronal plasticity and adaptive processes. Regulation of BDNF is complex and may reflect not only stress-specific mechanisms but also hormonal and emotional responses. For this reason we used, as an animal model of stress, a fish whose brain organization is very similar to that of higher vertebrates, but is generally considered free of emotional reactions. We provide a comprehensive characterization of BDNF gene in the Dicentrarchus labrax and its transcriptional, translational and post-translational regulation following acute stress. While total BDNF mRNA levels are unchanged, BDNF transcripts 1c and 1d resulted down regulated after acute stress. Acute stress induces also a significant increase in proBDNF levels and reduction in mature BDNF suggesting altered regulation of proBDNF proteolytic processing. Notably, we provide here the first evidence that fishes possess a simplified proteolytic regulation of BDNF since the pro28Kda form, generated by the SKI-1 protease in mammals, is absent in fishes because the cleavage site has first emerged in reptilians. Finally, we show that the proBDNF/totBDNF ratio is a highly predictive novel quantitative biomarker to detect stress in fishes with sensitivity = 100%, specificity = 87%, and Negative Predictive Value = 100%. The high predictivity of proBDNF/totBDNF ratio for stress in lower vertebrates indicates that processing of BDNF is a central mechanism in adaptation to stress and predicts that a similar regulation of pro/mature BDNF has likely been conserved throughout evolution of vertebrates from fish to man.

Is conflict adaptation due to active regulation or passive carry-over? Evidence from eye movements.

PubMed

Hubbard, Jason; Kuhns, David; Schäfer, Theo A J; Mayr, Ulrich

2017-03-01

Conflict-adaptation effects (i.e., reduced response-time costs on high-conflict trials following high-conflict trials) supposedly represent our cognitive system's ability to regulate itself according to current processing demands. However, currently it is not clear whether these effects reflect conflict-triggered, active regulation, or passive carry-over of previous-trial control settings. We used eye movements to examine whether the degree of experienced conflict modulates conflict-adaptation effects, as the conflict-triggered regulation view predicts. Across 2 experiments in which participants had to identify a target stimulus based on an endogenous cue while-on conflict trials-having to resist a sudden-onset distractor, we found a clear indication of conflict adaptation. This adaptation effect disappeared however, when participants inadvertently fixated the sudden-onset distractor on the previous trial-that is, when they experienced a high degree of conflict. This pattern of results suggests that conflict adaptation can be explained parsimoniously in terms of a broader memory process that retains recently adopted control settings across trials. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Is Conflict Adaptation due to Active Regulation or Passive Carry-Over? Evidence from Eye Movements

PubMed Central

Hubbard, Jason; Kuhns, David; Schäfer, Theo A.J.; Mayr, Ulrich

2017-01-01

Conflict-adaptation effects (i.e., reduced response-time costs on high-conflict trials following high-conflict trials) supposedly represent our cognitive system’s ability to regulate itself according to current processing demands. However, currently it is not clear whether these effects reflect conflict-triggered, active regulation, or passive carry-over of previous-trial control settings. We used eye movements to examine whether the degree of experienced conflict modulates conflict-adaptation effects, as the conflict-triggered regulation view predicts. Across two experiments in which participants had to identify a target stimulus based on an endogenous cue while––on conflict trials––having to resist a sudden-onset distractor, we found a clear indication of conflict adaptation. This adaptation effect disappeared however, when participants inadvertently fixated the sudden-onset distractor on the previous trial––that is, when they experienced a high degree of conflict. This pattern of results suggests that conflict adaptation can be explained parsimoniously in terms of a broader memory process that retains recently adopted control settings across trials. PMID:27656869

Single-Event Transient Testing of Low Dropout PNP Series Linear Voltage Regulators

NASA Technical Reports Server (NTRS)

Adell, Philippe; Allen, Gregory

2013-01-01

As demand for high-speed, on-board, digital-processing integrated circuits on spacecraft increases (field-programmable gate arrays and digital signal processors in particular), the need for the next generation point-of-load (POL) regulator becomes a prominent design issue. Shrinking process nodes have resulted in core rails dropping to values close to 1.0 V, drastically reducing margin to standard switching converters or regulators that power digital ICs. The goal of this task is to perform SET characterization of several commercial POL converters, and provide a discussion of the impact of these results to state-of-the-art digital processing IC through laser and heavy ion testing

Transcriptomic and functional analyses unveil the role of long non-coding RNAs in anthocyanin biosynthesis during sea buckthorn fruit ripening.

PubMed

Zhang, Guoyun; Chen, Daoguo; Zhang, Tong; Duan, Aiguo; Zhang, Jianguo; He, Caiyun

2018-06-04

Fruit ripening is a developmental process regulated by a complex network of endogenous and exogenous cues. Sea buckthorn is an excellent material for fruit ripening studies due to its dramatic ripening process and high contents of nutritional and anti-oxidant compounds in berries. Here, the whole transcriptome of sea buckthorn fruit at three development stages were analysed using multiple high-throughput sequencings. We assembled and annotated 9,008 long non-coding RNAs (lncRNAs) in sea buckthorn fruits, and identified 118 differentially expressed lncRNAs (DE-lncRNAs) and 32 differentially expressed microRNAs in fruit developmental process. In addition, we predicted 1,061 cis-regulated and 782 trans-regulated targets of DE-lncRNAs, and these DE-lncRNAs are specifically enriched in the biosynthesis of ascorbic acid, carotenoids and flavonoids. Moreover, the silencing of two lncRNAs (LNC1 and LNC2) in vivo and expression analysis revealed that LNC1 and LNC2 can act as endogenous target mimics of miR156a and miR828a to reduce SPL9 and induce MYB114 expression, respectively, which lead to increased and decreased anthocyanin content as revealed by high-performance liquid chromatography analysis. Our results present the first global functional analysis of lncRNA in sea buckthorn and provide two essential regulators of anthocyanin biosynthesis, which provides new insights into the regulation of fruit quality.

Transcriptomic characterization of cold acclimation in larval zebrafish

PubMed Central

2013-01-01

Background Temperature is one of key environmental parameters that affect the whole life of fishes and an increasing number of studies have been directed towards understanding the mechanisms of cold acclimation in fish. However, the adaptation of larvae to cold stress and the cold-specific transcriptional alterations in fish larvae remain largely unknown. In this study, we characterized the development of cold-tolerance in zebrafish larvae and investigated the transcriptional profiles under cold stress using RNA-seq. Results Pre-exposure of 96 hpf zebrafish larvae to cold stress (16°C) for 24 h significantly increased their survival rates under severe cold stress (12°C). RNA-seq generated 272 million raw reads from six sequencing libraries and about 92% of the processed reads were mapped to the reference genome of zebrafish. Differential expression analysis identified 1,431 up- and 399 down-regulated genes. Gene ontology enrichment analysis of cold-induced genes revealed that RNA splicing, ribosome biogenesis and protein catabolic process were the most highly overrepresented biological processes. Spliceosome, proteasome, eukaryotic ribosome biogenesis and RNA transport were the most highly enriched pathways for genes up-regulated by cold stress. Moreover, alternative splicing of 197 genes and promoter switching of 64 genes were found to be regulated by cold stress. A shorter isoform of stk16 that lacks 67 amino acids at the N-terminus was specifically generated by skipping the second exon in cold-treated larvae. Alternative promoter usage was detected for per3 gene under cold stress, which leading to a highly up-regulated transcript encoding a truncated protein lacking the C-terminal domains. Conclusions These findings indicate that zebrafish larvae possess the ability to build cold-tolerance under mild low temperature and transcriptional and post-transcriptional regulations are extensively involved in this acclimation process. PMID:24024969

The Predator becomes the Prey: Regulating the Ubiquitin System by Ubiquitylation and Degradation

PubMed Central

Weissman, Allan M.; Shabek, Nitzan; Ciechanover, Aaron

2012-01-01

Ubiquitylation (also known as ubiquitination) regulates essentially all intracellular processes in eukaryotes through highly specific, and often tightly spatially and temporally regulated, modification of numerous cellular proteins. Although most often associated with proteasomal degradation, ubiquitylation frequently serves non-proteolytic functions. In light of its central roles in cellular regulation, it has not been surprising to find that many of the components of the ubiquitin system itself are regulated by ubiquitylation. This observation has broad implications for pathophysiology. PMID:21860393

Boron transport in plants: co-ordinated regulation of transporters

PubMed Central

Miwa, Kyoko; Fujiwara, Toru

2010-01-01

Background The essentiality of boron (B) for plant growth was established >85 years ago. In the last decade, it has been revealed that one of the physiological roles of B is cross-linking the pectic polysaccharide rhamnogalacturonan II in primary cell walls. Borate cross-linking of pectic networks serves both for physical strength of cell walls and for cell adhesion. On the other hand, high concentrations of B are toxic to plant growth. To avoid deficiency and toxicity problems, it is important for plants to maintain their tissue B concentrations within an optimum range by regulating transport processes. Boron transport was long believed to be a passive, unregulated process, but the identification of B transporters has suggested that plants sense and respond to the B conditions and regulate transporters to maintain B homeostasis. Scope Transporters responsible for efficient B uptake by roots, xylem loading and B distribution among leaves have been described. These transporters are required under B limitation for efficient acquisition and utilization of B. Transporters important for tolerating high B levels in the environment have also been identified, and these transporters export B from roots back to the soil. Two types of transporters are involved in these processes: NIPs (nodulin-26-like intrinsic proteins), boric acid channels, and BORs, B exporters. It is demonstrated that the expression of genes encoding these transporters is finely regulated in response to B availability in the environment to ensure tissue B homeostasis. Furthermore, plants tolerant to stress produced by low B or high B in the environment can be generated through altered expression of these transporters. Conclusions The identification of the first B transporter led to the discovery that B transport was a process mediated not only by passive diffusion but also by transporters whose activity was regulated in response to B conditions. Now it is evident that plants sense internal and external B conditions and regulate B transport by modulating the expression and/or accumulation of these transporters. Results obtained in model plants are applicable to other plant species, and such knowledge may be useful in designing plants or crops tolerant to soils containing low or high B. PMID:20228086

microRNA-200b as a Switch for Inducible Adult Angiogenesis.

PubMed

Sinha, Mithun; Ghatak, Subhadip; Roy, Sashwati; Sen, Chandan K

2015-05-10

Angiogenesis is the process by which new blood vessels develop from a pre-existing vascular system. It is required for physiological processes such as developmental biology and wound healing. Angiogenesis also plays a crucial role in pathological conditions such as tumor progression. The underlying importance of angiogenesis necessitates a highly regulated process. Recent works have demonstrated that the process of angiogenesis is regulated by small noncoding RNA molecules called microRNAs (miRs). These miRs, collectively referred to as angiomiRs, have been reported to have a profound effect on the process of angiogenesis by acting as either pro-angiogenic or anti-angiogenic regulators. In this review, we will discuss the role of miR-200b as a regulator of angiogenesis. Once the process of angiogenesis is complete, anti-angiogenic miR-200b has been reported to provide necessary braking. Downregulation of miR-200b has been reported across various tumor types, as deregulated angiogenesis is necessary for tumor development. Transient downregulation of miR-200b in wounds drives wound angiogenesis. New insights and understanding of the molecular mechanism of regulation of angiogenesis by miR-200b has opened new avenues of possible therapeutic interventions to treat angiogenesis-related patho-physiological conditions. Antioxid. Redox Signal. 22, 1257-1272.

21 CFR 820.75 - Process validation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Process validation. 820.75 Section 820.75 Food and... QUALITY SYSTEM REGULATION Production and Process Controls § 820.75 Process validation. (a) Where the... validated with a high degree of assurance and approved according to established procedures. The validation...

21 CFR 820.75 - Process validation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Process validation. 820.75 Section 820.75 Food and... QUALITY SYSTEM REGULATION Production and Process Controls § 820.75 Process validation. (a) Where the... validated with a high degree of assurance and approved according to established procedures. The validation...

21 CFR 820.75 - Process validation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Process validation. 820.75 Section 820.75 Food and... QUALITY SYSTEM REGULATION Production and Process Controls § 820.75 Process validation. (a) Where the... validated with a high degree of assurance and approved according to established procedures. The validation...

21 CFR 820.75 - Process validation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Process validation. 820.75 Section 820.75 Food and... QUALITY SYSTEM REGULATION Production and Process Controls § 820.75 Process validation. (a) Where the... validated with a high degree of assurance and approved according to established procedures. The validation...

21 CFR 820.75 - Process validation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Process validation. 820.75 Section 820.75 Food and... QUALITY SYSTEM REGULATION Production and Process Controls § 820.75 Process validation. (a) Where the... validated with a high degree of assurance and approved according to established procedures. The validation...

Cell identity regulators link development and stress responses in the Arabidopsis root.

PubMed

Iyer-Pascuzzi, Anjali S; Jackson, Terry; Cui, Hongchang; Petricka, Jalean J; Busch, Wolfgang; Tsukagoshi, Hironaka; Benfey, Philip N

2011-10-18

Stress responses in plants are tightly coordinated with developmental processes, but interaction of these pathways is poorly understood. We used genome-wide assays at high spatiotemporal resolution to understand the processes that link development and stress in the Arabidopsis root. Our meta-analysis finds little evidence for a universal stress response. However, common stress responses appear to exist with many showing cell type specificity. Common stress responses may be mediated by cell identity regulators because mutations in these genes resulted in altered responses to stress. Evidence for a direct role for cell identity regulators came from genome-wide binding profiling of the key regulator SCARECROW, which showed binding to regulatory regions of stress-responsive genes. Coexpression in response to stress was used to identify genes involved in specific developmental processes. These results reveal surprising linkages between stress and development at cellular resolution, and show the power of multiple genome-wide data sets to elucidate biological processes. Copyright © 2011 Elsevier Inc. All rights reserved.

Transcriptional regulation of podocyte specification and differentiation.

PubMed

Quaggin, Susan E

2002-05-15

Glomerular visceral epithelial cells (podocytes) are highly specialized cells found in the vertebrate and invertebrate kidney and make up a major portion of the filtration barrier between blood and urinary spaces. During development, specification and differentiation of the podocyte lineage must be tightly orchestrated to produce highly specialized characteristics such as foot processes and slit diaphragms. Furthermore, podocytes are poised to direct incoming endothelial and mesangial cells during glomerular development. They express a number of growth factors that likely play a major role in these processes. Recent findings from transgenic and knockout mouse models and the identification of genes responsible for human podocyte disease have provided insight into transcriptional regulation of some of these processes. These transcription factors include Pax2, WT1 (the Wilms tumor suppressor gene), Pod1 (capsulin, epicardin), Kreisler (maf-1), lmx1b, and mf2. Furthermore, regulatory regions from a podocyte-restricted gene, NPHS1 (nephrin) that are required to direct podocyte-specific expression have been identified from both human and murine genes and provide a tool to further dissect the transcriptional regulation of podocyte-specific gene expression. This article reviews the present state of knowledge regarding transcriptional regulation of podocyte specification and differentiation. Copyright 2002 Wiley-Liss, Inc.

Design of Linear-Quadratic-Regulator for a CSTR process

NASA Astrophysics Data System (ADS)

Meghna, P. R.; Saranya, V.; Jaganatha Pandian, B.

2017-11-01

This paper aims at creating a Linear Quadratic Regulator (LQR) for a Continuous Stirred Tank Reactor (CSTR). A CSTR is a common process used in chemical industries. It is a highly non-linear system. Therefore, in order to create the gain feedback controller, the model is linearized. The controller is designed for the linearized model and the concentration and volume of the liquid in the reactor are kept at a constant value as required.

Inflorescence Development and the Role of LsFT in Regulating Bolting in Lettuce (Lactuca sativa L.).

PubMed

Chen, Zijing; Han, Yingyan; Ning, Kang; Ding, Yunyu; Zhao, Wensheng; Yan, Shuangshuang; Luo, Chen; Jiang, Xiaotang; Ge, Danfeng; Liu, Renyi; Wang, Qian; Zhang, Xiaolan

2017-01-01

Lettuce ( Lactuca sativa L.) is one of the most important leafy vegetable that is consumed during its vegetative growth. The transition from vegetative to reproductive growth is induced by high temperature, which has significant economic effect on lettuce production. However, the progression of floral transition and the molecular regulation of bolting are largely unknown. Here we morphologically characterized the inflorescence development and functionally analyzed the FLOWERING LOCUS T (LsFT) gene during bolting regulation in lettuce. We described the eight developmental stages during floral transition process. The expression of LsFT was negatively correlated with bolting in different lettuce varieties, and was promoted by heat treatment. Overexpression of LsFT could recover the late-flowering phenotype of ft-2 mutant. Knockdown of LsFT by RNA interference dramatically delayed bolting in lettuce, and failed to respond to high temperature. Therefore, this study dissects the process of inflorescence development and characterizes the role of LsFT in bolting regulation in lettuce.

Inflorescence Development and the Role of LsFT in Regulating Bolting in Lettuce (Lactuca sativa L.)

PubMed Central

Chen, Zijing; Han, Yingyan; Ning, Kang; Ding, Yunyu; Zhao, Wensheng; Yan, Shuangshuang; Luo, Chen; Jiang, Xiaotang; Ge, Danfeng; Liu, Renyi; Wang, Qian; Zhang, Xiaolan

2018-01-01

Lettuce (Lactuca sativa L.) is one of the most important leafy vegetable that is consumed during its vegetative growth. The transition from vegetative to reproductive growth is induced by high temperature, which has significant economic effect on lettuce production. However, the progression of floral transition and the molecular regulation of bolting are largely unknown. Here we morphologically characterized the inflorescence development and functionally analyzed the FLOWERING LOCUS T (LsFT) gene during bolting regulation in lettuce. We described the eight developmental stages during floral transition process. The expression of LsFT was negatively correlated with bolting in different lettuce varieties, and was promoted by heat treatment. Overexpression of LsFT could recover the late-flowering phenotype of ft-2 mutant. Knockdown of LsFT by RNA interference dramatically delayed bolting in lettuce, and failed to respond to high temperature. Therefore, this study dissects the process of inflorescence development and characterizes the role of LsFT in bolting regulation in lettuce. PMID:29403510

Whole genome-wide transcript profiling to identify differentially expressed genes associated with seed field emergence in two soybean low phytate mutants.

PubMed

Yuan, Fengjie; Yu, Xiaomin; Dong, Dekun; Yang, Qinghua; Fu, Xujun; Zhu, Shenlong; Zhu, Danhua

2017-01-18

Seed germination is important to soybean (Glycine max) growth and development, ultimately affecting soybean yield. A lower seed field emergence has been the main hindrance for breeding soybeans low in phytate. Although this reduction could be overcome by additional breeding and selection, the mechanisms of seed germination in different low phytate mutants remain unknown. In this study, we performed a comparative transcript analysis of two low phytate soybean mutants (TW-1 and TW-1-M), which have the same mutation, a 2 bp deletion in GmMIPS1, but show a significant difference in seed field emergence, TW-1-M was higher than that of TW-1 . Numerous genes analyzed by RNA-Seq showed markedly different expression levels between TW-1-M and TW-1 mutants. Approximately 30,000-35,000 read-mapped genes and ~21000-25000 expressed genes were identified for each library. There were ~3900-9200 differentially expressed genes (DEGs) in each contrast library, the number of up-regulated genes was similar with down-regulated genes in the mutant TW-1and TW-1-M. Gene ontology functional categories of DEGs indicated that the ethylene-mediated signaling pathway, the abscisic acid-mediated signaling pathway, response to hormone, ethylene biosynthetic process, ethylene metabolic process, regulation of hormone levels, and oxidation-reduction process, regulation of flavonoid biosynthetic process and regulation of abscisic acid-activated signaling pathway had high correlations with seed germination. In total, 2457 DEGs involved in the above functional categories were identified. Twenty-two genes with 20 biological functions were the most highly up/down- regulated (absolute value Log2FC >5) in the high field emergence mutant TW-1-M and were related to metabolic or signaling pathways. Fifty-seven genes with 36 biological functions had the greatest expression abundance (FRPM >100) in germination-related pathways. Seed germination in the soybean low phytate mutants is a very complex process, which involves a series of physiological, morphological and transcriptional changes. Compared with TW-1, TW-1-M had a very different gene expression profile, which included genes related to plant hormones, antioxidation, anti-stress and energy metabolism processes. Our research provides a molecular basis for understanding germination mechanisms, and is also an important resource for the genetic analysis of germination in low phytate crops. Plant hormone- and antioxidation-related genes might strongly contribute to the high germination rate in the TW-1-M mutant.

Emotion Regulation and Emotion Work: Two Sides of the Same Coin?

PubMed Central

von Scheve, Christian

2012-01-01

This contribution links psychological models of emotion regulation to sociological accounts of emotion work to demonstrate the extent to which emotion regulation is systematically shaped by culture and society. I first discuss a well-established two-factor process model of emotion regulation and argue that a substantial proportion of emotion regulatory goals are derived from emotion norms. In contrast to universal emotion values and hedonic preferences, emotion norms are highly specific to social situations and institutional contexts. This specificity is determined by social cognitive processes of categorization and guided by framing rules. Second, I argue that the possibilities for antecedent-focused regulation, in particular situation selection and modification, are not arbitrarily available to individuals. Instead, they depend on economic, cultural, and social resources. I suggest that the systematic and unequal distribution of these resources in society leads to discernible patterns of emotion and emotion regulation across groups of individuals. PMID:23181041

Role of sugars under abiotic stress.

PubMed

Sami, Fareen; Yusuf, Mohammad; Faizan, Mohammad; Faraz, Ahmad; Hayat, Shamsul

2016-12-01

Sugars are the most important regulators that facilitate many physiological processes, such as photosynthesis, seed germination, flowering, senescence, and many more under various abiotic stresses. Exogenous application of sugars in low concentration promote seed germination, up regulates photosynthesis, promotes flowering, delayed senescence under various unfavorable environmental conditions. However, high concentration of sugars reverses all these physiological process in a concentration dependent manner. Thus, this review focuses the correlation between sugars and their protective functions in several physiological processes against various abiotic stresses. Keeping in mind the multifaceted role of sugars, an attempt has been made to cover the role of sugar-regulated genes associated with photosynthesis, seed germination and senescence. The concentration of sugars determines the expression of these sugar-regulated genes. This review also enlightens the interaction of sugars with several phytohormones, such as abscisic acid, ethylene, cytokinins and gibberellins and its effect on their biosynthesis under abiotic stress conditions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Cut! that’s a wrap: regulating negative emotion by ending emotion-eliciting situations

PubMed Central

Vujovic, Lara; Opitz, Philipp C.; Birk, Jeffrey L.; Urry, Heather L.

2014-01-01

Little is known about the potentially powerful set of emotion regulation (ER) processes that target emotion-eliciting situations. We thus studied the decision to end emotion-eliciting situations in the laboratory. We hypothesized that people would try to end negative situations more frequently than neutral situations to regulate distress. In addition, motivated by the selection, optimization, and compensation with ER framework, we hypothesized that failed attempts to end the situation would prompt either (a) greater negative emotion or (b) compensatory use of a different ER process, attentional deployment (AD). Fifty-eight participants (18–26 years old, 67% women) viewed negative and neutral pictures and pressed a key whenever they wished to stop viewing them. After key press, the picture disappeared (“success”) or stayed (“failure”) on screen. To index emotion, we measured corrugator and electrodermal activity, heart rate, and self-reported arousal. To index overt AD, we measured eye gaze. As their reason for ending the situation, participants more frequently reported being upset by high- than low-arousal negative pictures; they more frequently reported being bored by low- than high-arousal neutral pictures. Nevertheless, participants’ negative emotional responding did not increase in the context of ER failure nor did they use overt AD as a compensatory ER strategy. We conclude that situation-targeted ER processes are used to regulate emotional responses to high-arousal negative and low-arousal neutral situations; ER processes other than overt AD may be used to compensate for ER failure in this context. PMID:24592251

Adolescent Substance Use & Psychopathology: Interactive Effects of Cortisol Reactivity and Emotion Regulation

PubMed Central

Turpyn, Caitlin C.; Hansen, Amysue; Jacangelo, Juliana; Chaplin, Tara M.

2015-01-01

How are emotional processes associated with the increased rates of substance use and psychological disorders commonly observed during adolescence? An index of emotion-related physiological arousal—cortisol reactivity—and subjective emotion regulation have both been independently linked to substance use and psychological difficulties among youth. The current study (N = 134 adolescents) sought to elucidate the interactive effects of cortisol reactivity following a stressful parent–child interaction task and self-reported emotion regulation ability on adolescents’ substance use and externalizing and internalizing behavior problems. Results revealed that adolescents with low levels of cortisol reactivity and high emotion regulation difficulties were more likely to use substances, and also had the highest parent-reported symptoms of oppositional defiant disorder. With respect to internalizing symptoms, high emotion-related physiological reactivity coupled with high emotion regulation difficulties were associated with higher self-reported major depression symptoms among youth. Findings reveal that different profiles of HPA axis arousal and emotion regulation are associated with substance use and symptoms of psychopathology among adolescents. PMID:27330232

Medical Device Regulation: A Comparison of the United States and the European Union.

PubMed

Maak, Travis G; Wylie, James D

2016-08-01

Medical device regulation is a controversial topic in both the United States and the European Union. Many physicians and innovators in the United States cite a restrictive US FDA regulatory process as the reason for earlier and more rapid clinical advances in Europe. The FDA approval process mandates that a device be proved efficacious compared with a control or be substantially equivalent to a predicate device, whereas the European Union approval process mandates that the device perform its intended function. Stringent, peer-reviewed safety data have not been reported. However, after recent high-profile device failures, political pressure in both the United States and the European Union has favored more restrictive approval processes. Substantial reforms of the European Union process within the next 5 to 10 years will result in a more stringent approach to device regulation, similar to that of the FDA. Changes in the FDA regulatory process have been suggested but are not imminent.

Matrix metalloproteinase processing of signaling molecules to regulate inflammation.

PubMed

Butler, Georgina S; Overall, Christopher M

2013-10-01

Inflammation is a complex and highly regulated process that facilitates the clearance of pathogens and mediates tissue repair. Failure to resolve inflammation can lead to chronic inflammatory diseases such as periodontitis. Matrix metalloproteinases are generally thought to be detrimental in disease because degradation of extracellular matrix contributes to pathology. However, proteomic techniques (degradomics) are revealing that matrix metalloproteinases process a diverse array of substrates and therefore have a broad range of functions. Many matrix metalloproteinase substrates modulate inflammation and hence, by processing these proteins, matrix metalloproteinases can orchestrate the inflammatory response. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Robust interval-based regulation for anaerobic digestion processes.

PubMed

Alcaraz-González, V; Harmand, J; Rapaport, A; Steyer, J P; González-Alvarez, V; Pelayo-Ortiz, C

2005-01-01

A robust regulation law is applied to the stabilization of a class of biochemical reactors exhibiting partially known highly nonlinear dynamic behavior. An uncertain environment with the presence of unknown inputs is considered. Based on some structural and operational conditions, this regulation law is shown to exponentially stabilize the aforementioned bioreactors around a desired set-point. This approach is experimentally applied and validated on a pilot-scale (1 m3) anaerobic digestion process for the treatment of raw industrial wine distillery wastewater where the objective is the regulation of the chemical oxygen demand (COD) by using the dilution rate as the manipulated variable. Despite large disturbances on the input COD and state and parametric uncertainties, this regulation law gave excellent performances leading the output COD towards its set-point and keeping it inside a pre-specified interval.

The expression of PTEN in the development of mouse cochlear lateral wall.

PubMed

Dong, Y; Sui, L; Yamaguchi, F; Kamitori, K; Hirata, Y; Hossain, A; Noguchi, C; Katagi, A; Nishio, M; Suzuki, A; Lou, X; Tokuda, M

2014-01-31

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene that regulates various cell processes including proliferation, growth, synaptogenesis, neural and glioma stem/progenitor cell renewal. In addition, PTEN can regulate sensory cell proliferation and differentiation of hair bundles in the mammalian cochlea. In this study we use immunofluorescence, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) to reveal the expression of PTEN in the developing cochlear lateral wall, which is crucial for regulating K(+) homeostasis. Relatively high levels of PTEN are initially expressed in the marginal cells (MCs) of the lateral wall at embryonic day (E) 17.5 when they start to differentiate. Similarly high levels are subsequently expressed in differentiating root cells (RCs) at postnatal day (P) 3 and then in spiral ligament fibrocytes (SLFs) at P 10. In the mature cochlea, PTEN expression is low or undetectable in MCs and SLFs but it remains high in RCs and their processes. The expression pattern for PTEN in the developing lateral wall suggests that it plays a critical role in the differentiation of the cellular pathways that regulate K(+) homeostasis in the cochlea. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

BaHigh-force magnetic tweezers with force feedback for biological applications

NASA Astrophysics Data System (ADS)

Kollmannsberger, Philip; Fabry, Ben

2007-11-01

Magnetic micromanipulation using magnetic tweezers is a versatile biophysical technique and has been used for single-molecule unfolding, rheology measurements, and studies of force-regulated processes in living cells. This article describes an inexpensive magnetic tweezer setup for the application of precisely controlled forces up to 100nN onto 5μm magnetic beads. High precision of the force is achieved by a parametric force calibration method together with a real-time control of the magnetic tweezer position and current. High forces are achieved by bead-magnet distances of only a few micrometers. Applying such high forces can be used to characterize the local viscoelasticity of soft materials in the nonlinear regime, or to study force-regulated processes and mechanochemical signal transduction in living cells. The setup can be easily adapted to any inverted microscope.

High-force magnetic tweezers with force feedback for biological applications.

PubMed

Kollmannsberger, Philip; Fabry, Ben

2007-11-01

Magnetic micromanipulation using magnetic tweezers is a versatile biophysical technique and has been used for single-molecule unfolding, rheology measurements, and studies of force-regulated processes in living cells. This article describes an inexpensive magnetic tweezer setup for the application of precisely controlled forces up to 100 nN onto 5 microm magnetic beads. High precision of the force is achieved by a parametric force calibration method together with a real-time control of the magnetic tweezer position and current. High forces are achieved by bead-magnet distances of only a few micrometers. Applying such high forces can be used to characterize the local viscoelasticity of soft materials in the nonlinear regime, or to study force-regulated processes and mechanochemical signal transduction in living cells. The setup can be easily adapted to any inverted microscope.

Role of Arcuate Nucleus in the Regulation of Feeding Behavior in the Process of Altitude Acclimatization in Rats.

PubMed

Liu, Xiang-Wen; Yin, Jie; Ma, Qi-Sheng; Qi, Chu-Chu; Mu, Ji-Ying; Zhang, Lang; Gao, Li-Ping; Jing, Yu-Hong

2017-09-01

Liu, Xiang-Wen, Jie Yin, Qi-Sheng Ma, Chu-Chu Qi, Ji-Ying Mu, Lang Zhang, Li-Ping Gao, and Yu-Hong Jing. Role of arcuate nucleus in the regulation of feeding behavior in the process of altitude acclimatization in rats. High Alt Med Biol. 18:234-241, 2017.-Highly efficient energy utilization and metabolic homeostasis maintenance rely on neuromodulation. Altitude exposure is known to stimulate neuroendocrine systems to respond to acute hypoxia and adaptive acclimatization. However, limited data on how the adaptive regulation of the arcuate nucleus performs in the process of altitude acclimatization are available. In the present study, male Sprague Dawley rats were transported to Huashixia, Qinghai (with an altitude of 4400 m) from Xian (with an altitude of 300 m) by air; rats were consistently raised in Xian as control. Food uptake and body weight were measured consecutively after being subjected to high-altitude condition. Contents of plasma leptin and ghrelin were analyzed by the Enzyme Linked Immunosorbent Assay (ELISA) Kits. Brain coronal sections were obtained, and neuropeptide Y (NPY), proopiomelanocotin (POMC), and c-fos immunoreactivity in arcuate nucleus were observed. Arcuate nucleus was isolated from the hypothalamus, and the mRNA of NPY and POMC were measured by quantitative real-time polymerase chain reaction. Our results showed both food consumption and body weight decreased in the high plateau compared with rats raised in the low-altitude condition. Plasma leptin increased at the early stage, and ghrelin decreased at a later stage after reaching the high plateau. The peak of c-fos immunoreactivity in the arcuate nucleus was at day 3 after reaching the high plateau. The expression level of NPY increased, and POMC decreased in the arcuate nucleus at day 7 after reaching the high plateau compared with the plain control group. These results indicate that the arcuate nucleus of hypothalamus performs an important function in regulating feeding behavior during altitude acclimatization. Our study suggested that altitude acclimation is regulated by the hypothalamus that received leptin and ghrelin signals to response by its microcircuit, including NPY- and POMC-neurons in the arcuate nucleus.

Automatic Processes in Self-Regulation: Implications for Alcohol Interventions

ERIC Educational Resources Information Center

Palfai, Tibor

2004-01-01

A number of learning-based interventions for problem drinking have emphasized the importance of behavioral self-control skills to help manage responses to high-risk cues. Self-management interventions typically have been based on the premise that effective self-regulation involves the use of conscious, controlled strategies to override habitual…

System simulation of direct-current speed regulation based on Simulink

NASA Astrophysics Data System (ADS)

Yang, Meiying

2018-06-01

Many production machines require the smooth adjustment of speed in a certain range In the process of modern industrial production, and require good steady-state and dynamic performance. Direct-current speed regulation system with wide speed regulation range, small relative speed variation, good stability, large overload capacity, can bear the frequent impact load, can realize stepless rapid starting-braking and inversion of frequency and other good dynamic performances, can meet the different kinds of special operation requirements in production process of automation system. The direct-current power drive system is almost always used in the field of drive technology of high performance for a long time.

Trust and technology: the social foundations of aviation regulation.

PubMed

Downer, John

2010-03-01

This paper looks at the dilemmas posed by 'expertise' in high-technology regulation by examining the US Federal Aviation Administration's (FAA) 'type-certification' process, through which they evaluate new designs of civil aircraft. It observes that the FAA delegate a large amount of this work to the manufacturers themselves, and discusses why they do this by invoking arguments from the sociology of science and technology. It suggests that - contrary to popular portrayal - regulators of high technologies face an inevitable epistemic barrier when making technological assessments, which forces them to delegate technical questions to people with more tacit knowledge, and hence to 'regulate' at a distance by evaluating 'trust' rather than 'technology'. It then unravels some of the implications of this and its relation to our theories of regulation and 'regulatory capture'.

microRNA–200b as a Switch for Inducible Adult Angiogenesis

PubMed Central

Sinha, Mithun; Ghatak, Subhadip; Roy, Sashwati

2015-01-01

Abstract Significance: Angiogenesis is the process by which new blood vessels develop from a pre-existing vascular system. It is required for physiological processes such as developmental biology and wound healing. Angiogenesis also plays a crucial role in pathological conditions such as tumor progression. The underlying importance of angiogenesis necessitates a highly regulated process. Recent Advances: Recent works have demonstrated that the process of angiogenesis is regulated by small noncoding RNA molecules called microRNAs (miRs). These miRs, collectively referred to as angiomiRs, have been reported to have a profound effect on the process of angiogenesis by acting as either pro-angiogenic or anti-angiogenic regulators. Critical Issues: In this review, we will discuss the role of miR-200b as a regulator of angiogenesis. Once the process of angiogenesis is complete, anti-angiogenic miR-200b has been reported to provide necessary braking. Downregulation of miR-200b has been reported across various tumor types, as deregulated angiogenesis is necessary for tumor development. Transient downregulation of miR-200b in wounds drives wound angiogenesis. Future Directions: New insights and understanding of the molecular mechanism of regulation of angiogenesis by miR-200b has opened new avenues of possible therapeutic interventions to treat angiogenesis-related patho-physiological conditions. Antioxid. Redox Signal. 22, 1257–1272. PMID:25761972

Integrating emotion regulation and emotional intelligence traditions: a meta-analysis

PubMed Central

Peña-Sarrionandia, Ainize; Mikolajczak, Moïra; Gross, James J.

2015-01-01

Two relatively independent research traditions have developed that address emotion management. The first is the emotion regulation (ER) tradition, which focuses on the processes which permit individuals to influence which emotions they have, when they have them, and how they experience and express these emotions. The second is the emotional intelligence (EI) tradition, which focuses—among other things—on individual differences in ER. To integrate these two traditions, we employed the process model of ER (Gross, 1998b) to review the literature on EI. Two key findings emerged. First, high EI individuals shape their emotions from the earliest possible point in the emotion trajectory and have many strategies at their disposal. Second, high EI individuals regulate their emotions successfully when necessary but they do so flexibly, thereby leaving room for emotions to emerge. We argue that ER and EI traditions stand to benefit substantially from greater integration. PMID:25759676

Down-regulation of respiration in pear fruit depends on temperature.

PubMed

Ho, Quang Tri; Hertog, Maarten L A T M; Verboven, Pieter; Ambaw, Alemayehu; Rogge, Seppe; Verlinden, Bert E; Nicolaï, Bart M

2018-04-09

The respiration rate of plant tissues decreases when the amount of available O2 is reduced. There is, however, a debate on whether the respiration rate is controlled either by diffusion limitation of oxygen or through regulatory processes at the level of the transcriptome. We used experimental and modelling approaches to demonstrate that both diffusion limitation and metabolic regulation affect the response of respiration of bulky plant organs such as fruit to reduced O2 levels in the surrounding atmosphere. Diffusion limitation greatly affects fruit respiration at high temperature, but at low temperature respiration is reduced through a regulatory process, presumably a response to a signal generated by a plant oxygen sensor. The response of respiration to O2 is time dependent and is highly sensitive, particularly at low O2 levels in the surrounding atmosphere. Down-regulation of the respiration at low temperatures may save internal O2 and relieve hypoxic conditions in the fruit.

The impact of pre-existing anxiety on affective and cognitive processing of a Virtual Reality analogue trauma.

PubMed

Schweizer, Tina; Schmitz, Julian; Plempe, Laura; Sun, Dali; Becker-Asano, Christian; Leonhart, Rainer; Tuschen-Caffier, Brunna

2017-01-01

Dysfunctional processing of traumatic events may be in particular related to high trait anxiety as a pre-traumatic risk factor for the development of post-traumatic stress disorder (PTSD). However, as this has rarely been investigated in prospective, experimental studies, we aimed to analyse the association between high trait anxiety and affective as well as cognitive processing of stress using a new prospective Virtual Reality analogue trauma paradigm to overcome limitations of retrospective or current analogue designs. Individuals with high and low trait anxiety (N = 80) were exposed to a multi-sensory Virtual Reality emergency scenario while psychophysiological stress response, emotion regulation and intrusive memories were assessed. Our results showed that high trait anxiety individuals display increased (i) subjective stress responses, (ii) emotion dysregulation and (iii) intrusive memories upon VR analogue trauma exposure. In particular, our sample of high trait anxiety individuals displayed limited access to different emotion regulation strategies as well as increased worry and rumination regarding perceived intrusive memories. Considering the complex interplay of multiple risk factors, our findings suggests that peri-traumatic affective processing seems to mediate high trait anxiety and post-traumatic intrusive memories thereby pointing out the central role of peri-traumatic processes for intrusion development. In addition, HA as a modulating pre-traumatic risk factor might further increase the risk of later dysfunctional processing of an analogue trauma by interacting with factors of affective processing during analogue trauma exposure. Implications of these findings which may contribute to a higher risk to develop PTSD are discussed.

The impact of pre-existing anxiety on affective and cognitive processing of a Virtual Reality analogue trauma

PubMed Central

Schmitz, Julian; Plempe, Laura; Sun, Dali; Becker-Asano, Christian; Leonhart, Rainer; Tuschen-Caffier, Brunna

2017-01-01

Dysfunctional processing of traumatic events may be in particular related to high trait anxiety as a pre-traumatic risk factor for the development of post-traumatic stress disorder (PTSD). However, as this has rarely been investigated in prospective, experimental studies, we aimed to analyse the association between high trait anxiety and affective as well as cognitive processing of stress using a new prospective Virtual Reality analogue trauma paradigm to overcome limitations of retrospective or current analogue designs. Individuals with high and low trait anxiety (N = 80) were exposed to a multi-sensory Virtual Reality emergency scenario while psychophysiological stress response, emotion regulation and intrusive memories were assessed. Our results showed that high trait anxiety individuals display increased (i) subjective stress responses, (ii) emotion dysregulation and (iii) intrusive memories upon VR analogue trauma exposure. In particular, our sample of high trait anxiety individuals displayed limited access to different emotion regulation strategies as well as increased worry and rumination regarding perceived intrusive memories. Considering the complex interplay of multiple risk factors, our findings suggests that peri-traumatic affective processing seems to mediate high trait anxiety and post-traumatic intrusive memories thereby pointing out the central role of peri-traumatic processes for intrusion development. In addition, HA as a modulating pre-traumatic risk factor might further increase the risk of later dysfunctional processing of an analogue trauma by interacting with factors of affective processing during analogue trauma exposure. Implications of these findings which may contribute to a higher risk to develop PTSD are discussed. PMID:29287111

Regulating approaches to learning: Testing learning strategy convergences across a year at university.

PubMed

Fryer, Luke K; Vermunt, Jan D

2018-03-01

Contemporary models of student learning within higher education are often inclusive of processing and regulation strategies. Considerable research has examined their use over time and their (person-centred) convergence. The longitudinal stability/variability of learning strategy use, however, is poorly understood, but essential to supporting student learning across university experiences. Develop and test a person-centred longitudinal model of learning strategies across the first-year university experience. Japanese university students (n = 933) completed surveys (deep and surface approaches to learning; self, external, and lack of regulation) at the beginning and end of their first year. Following invariance and cross-sectional tests, latent profile transition analysis (LPTA) was undertaken. Initial difference testing supported small but significant differences for self-/external regulation. Fit indices supported a four-group model, consistent across both measurement points. These subgroups were labelled Low Quality (low deep approaches and self-regulation), Low Quantity (low strategy use generally), Average (moderate strategy use), and High Quantity (intense use of all strategies) strategies. The stability of these groups ranged from stable to variable: Average (93% stayers), Low Quality (90% stayers), High Quantity (72% stayers), and Low Quantity (40% stayers). The three largest transitions presented joint shifts in processing/regulation strategy preference across the year, from adaptive to maladaptive and vice versa. Person-centred longitudinal findings presented patterns of learning transitions that different students experience during their first year at university. Stability/variability of students' strategy use was linked to the nature of initial subgroup membership. Findings also indicated strong connections between processing and regulation strategy changes across first-year university experiences. Implications for theory and practice are discussed. © 2017 The British Psychological Society.

Connexin43high prostate cancer cells induce endothelial connexin43 up-regulation through the activation of intercellular ERK1/2-dependent signaling axis.

PubMed

Piwowarczyk, Katarzyna; Paw, Milena; Ryszawy, Damian; Rutkowska-Zapała, Magdalena; Madeja, Zbigniew; Siedlar, Maciej; Czyż, Jarosław

2017-06-01

Connexin(Cx)43 regulates the invasive potential of prostate cancer cells and participates in their extravasation. To address the role of endothelial Cx43 in this process, we analyzed Cx43 regulation in human umbilical vein endothelial cells in the proximity of Cx43 high (DU-145 and MAT-LyLu) and Cx43 low prostate cancer cells (PC-3 and AT-2). Endothelial Cx43 up-regulation was observed during the diapedesis of DU-145 and MAT-LyLu cells. This process was attenuated by transient Cx43 silencing in cancer cells and by chemical inhibition of ERK1/2-dependent signaling in endothelial cells. Cx43 expression in endothelial cells was insensitive to the inhibition of gap junctional intercellular coupling between Cx43 high prostate cancer and endothelial cells by 18α-glycyrrhetinic acid. Instead, endothelial Cx43 up-regulation was correlated with the local contraction of endothelial cells and with their activation in the proximity of Cx43 high DU-145 and MAT-LyLu cells. It was also sensitive to pro-inflammatory factors secreted by peripheral blood monocytes, such as TNFα. In contrast to Cx43 low AT-2 cells, Cx43 low PC-3 cells produced angioactive factors that locally activated the endothelial cells in the absence of endothelial Cx43 up-regulation. Collectively, these data show that Cx43 low and Cx43 high prostate cancer cells can adapt discrete, Cx43-independent and Cx43-dependent strategies of diapedesis. Our observations identify a novel strategy of prostate cancer cell diapedesis, which depends on the activation of intercellular Cx43/ERK1/2/Cx43 signaling axis at the interfaces between Cx43 high prostate cancer and endothelial cells. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Genes uniquely expressed in human growth plate chondrocytes uncover a distinct regulatory network.

PubMed

Li, Bing; Balasubramanian, Karthika; Krakow, Deborah; Cohn, Daniel H

2017-12-20

Chondrogenesis is the earliest stage of skeletal development and is a highly dynamic process, integrating the activities and functions of transcription factors, cell signaling molecules and extracellular matrix proteins. The molecular mechanisms underlying chondrogenesis have been extensively studied and multiple key regulators of this process have been identified. However, a genome-wide overview of the gene regulatory network in chondrogenesis has not been achieved. In this study, employing RNA sequencing, we identified 332 protein coding genes and 34 long non-coding RNA (lncRNA) genes that are highly selectively expressed in human fetal growth plate chondrocytes. Among the protein coding genes, 32 genes were associated with 62 distinct human skeletal disorders and 153 genes were associated with skeletal defects in knockout mice, confirming their essential roles in skeletal formation. These gene products formed a comprehensive physical interaction network and participated in multiple cellular processes regulating skeletal development. The data also revealed 34 transcription factors and 11,334 distal enhancers that were uniquely active in chondrocytes, functioning as transcriptional regulators for the cartilage-selective genes. Our findings revealed a complex gene regulatory network controlling skeletal development whereby transcription factors, enhancers and lncRNAs participate in chondrogenesis by transcriptional regulation of key genes. Additionally, the cartilage-selective genes represent candidate genes for unsolved human skeletal disorders.

Distinct roles for Arp2/3 regulators in actin assembly and endocytosis.

PubMed

Galletta, Brian J; Chuang, Dennis Y; Cooper, John A

2008-01-01

The Arp2/3 complex is essential for actin assembly and motility in many cell processes, and a large number of proteins have been found to bind and regulate it in vitro. A critical challenge is to understand the actions of these proteins in cells, especially in settings where multiple regulators are present. In a systematic study of the sequential multicomponent actin assembly processes that accompany endocytosis in yeast, we examined and compared the roles of WASp, two type-I myosins, and two other Arp2/3 activators, along with that of coronin, which is a proposed inhibitor of Arp2/3. Quantitative analysis of high-speed fluorescence imaging revealed individual functions for the regulators, manifested in part by novel phenotypes. We conclude that Arp2/3 regulators have distinct and overlapping roles in the processes of actin assembly that drive endocytosis in yeast. The formation of the endocytic actin patch, the creation of the endocytic vesicle, and the movement of the vesicle into the cytoplasm display distinct dependencies on different Arp2/3 regulators. Knowledge of these roles provides insight into the in vivo relevance of the dendritic nucleation model for actin assembly.

On the dynamics of implicit emotion regulation: counter-regulation after remembering events of high but not of low emotional intensity.

PubMed

Schwager, Susanne; Rothermund, Klaus

2014-01-01

Valence biases in attention allocation were assessed after remembering positive or negative personal events that were either still emotionally hot or to which the person had already adapted psychologically. Differences regarding the current state of psychological adjustment were manipulated experimentally by instructing participants to recall distant vs. recent events (Experiment 1) or affectively hot events vs. events to which the person had accommodated already (Experiment 2). Valence biases in affective processing were measured with a valence search task. Processes of emotional counter-regulation (i.e., attention allocation to stimuli of opposite valence to the emotional event) were elicited by remembering affectively hot events, whereas congruency effects (i.e., attention allocation to stimuli of the same valence as the emotional event) were obtained for events for which a final appraisal had already been established. The results of our study help to resolve conflicting findings from the literature regarding congruent vs. incongruent effects of remembering emotional events on affective processing. We discuss implications of our findings for the conception of emotions and for the dynamics of emotion regulation processes.

How do older adult drivers self-regulate? Characteristics of self-regulation classes defined by latent class analysis.

PubMed

Bergen, Gwen; West, Bethany A; Luo, Feijun; Bird, Donna C; Freund, Katherine; Fortinsky, Richard H; Staplin, Loren

2017-06-01

Motor-vehicle crashes were the second leading cause of injury death for adults aged 65-84years in 2014. Some older drivers choose to self-regulate their driving to maintain mobility while reducing driving risk, yet the process remains poorly understood. Data from 729 older adults (aged ≥60years) who joined an older adult ride service program between April 1, 2010 and November 8, 2013 were analyzed to define and describe classes of driving self-regulation. Latent class analysis was employed to characterize older adult driving self-regulation classes using driving frequency and avoidance of seven driving situations. Logistic regression was used to explore associations between characteristics affecting mobility and self-regulation class. Three classes were identified (low, medium, and high self-regulation). High self-regulating participants reported the highest proportion of always avoiding seven risky driving situations and the lowest driving frequency followed by medium and low self-regulators. Those who were female, aged 80years or older, visually impaired, assistive device users, and those with special health needs were more likely to be high self-regulating compared with low self-regulating. Avoidance of certain driving situations and weekly driving frequency are valid indicators for describing driving self-regulation classes in older adults. Understanding the unique characteristics and mobility limitations of each class can guide optimal transportation strategies for older adults. Published by Elsevier Ltd.

Safety Considerations in the Chemical Process Industries

NASA Astrophysics Data System (ADS)

Englund, Stanley M.

There is an increased emphasis on chemical process safety as a result of highly publicized accidents. Public awareness of these accidents has provided a driving force for industry to improve its safety record. There has been an increasing amount of government regulation.

Regulation of T cell receptor complex-mediated signaling by ubiquitin and ubiquitin-like modifications.

PubMed

Friend, Samantha F; Deason-Towne, Francina; Peterson, Lisa K; Berger, Allison J; Dragone, Leonard L

2014-01-01

Post-translational protein modifications are a dynamic method of regulating protein function in response to environmental signals. As with any cellular process, T cell receptor (TCR) complex-mediated signaling is highly regulated, since the strength and duration of TCR-generated signals governs T cell development and activation. While regulation of TCR complex-mediated signaling by phosphorylation has been well studied, regulation by ubiquitin and ubiquitin-like modifiers is still an emerging area of investigation. This review will examine how ubiquitin, E3 ubiquitin ligases, and other ubiquitin-like modifications such as SUMO and NEDD8 regulate TCR complex-mediated signaling.

Regulation of T cell receptor complex-mediated signaling by ubiquitin and ubiquitin-like modifications

PubMed Central

Friend, Samantha F; Deason-Towne, Francina; Peterson, Lisa K; Berger, Allison J; Dragone, Leonard L

2014-01-01

Post-translational protein modifications are a dynamic method of regulating protein function in response to environmental signals. As with any cellular process, T cell receptor (TCR) complex-mediated signaling is highly regulated, since the strength and duration of TCR-generated signals governs T cell development and activation. While regulation of TCR complex-mediated signaling by phosphorylation has been well studied, regulation by ubiquitin and ubiquitin-like modifiers is still an emerging area of investigation. This review will examine how ubiquitin, E3 ubiquitin ligases, and other ubiquitin-like modifications such as SUMO and NEDD8 regulate TCR complex-mediated signaling. PMID:25628960

Bringing RNA Interference (RNAi) into the High School Classroom

ERIC Educational Resources Information Center

Sengupta, Sibani

2013-01-01

RNA interference (abbreviated RNAi) is a relatively new discovery in the field of mechanisms that serve to regulate gene expression (a.k.a. protein synthesis). Gene expression can be regulated at the transcriptional level (mRNA production, processing, or stability) and at the translational level (protein synthesis). RNAi acts in a gene-specific…

Emotion Regulation Difficulties, Youth-Adult Relationships, and Suicide Attempts among High School Students in Underserved Communities

ERIC Educational Resources Information Center

Pisani, Anthony R.; Wyman, Peter A.; Petrova, Mariya; Schmeelk-Cone, Karen; Goldston, David B.; Xia, Yinglin; Gould, Madelyn S.

2013-01-01

To develop and refine interventions to prevent youth suicide, knowledge is needed about specific processes that reduce risk at a population level. Using a cross-sectional design, the present study tested hypotheses regarding associations between self-reported suicide attempts, emotion regulation difficulties, and positive youth-adult relationships…

High-Throughput Sequencing of Small RNA Transcriptomes in Maize Kernel Identifies miRNAs Involved in Embryo and Endosperm Development.

PubMed

Xing, Lijuan; Zhu, Ming; Zhang, Min; Li, Wenzong; Jiang, Haiyang; Zou, Junjie; Wang, Lei; Xu, Miaoyun

2017-12-14

Maize kernel development is a complex biological process that involves the temporal and spatial expression of many genes and fine gene regulation at a transcriptional and post-transcriptional level, and microRNAs (miRNAs) play vital roles during this process. To gain insight into miRNA-mediated regulation of maize kernel development, a deep-sequencing technique was used to investigate the dynamic expression of miRNAs in the embryo and endosperm at three developmental stages in B73. By miRNA transcriptomic analysis, we characterized 132 known miRNAs and six novel miRNAs in developing maize kernel, among which, 15 and 14 miRNAs were commonly differentially expressed between the embryo and endosperm at 9 days after pollination (DAP), 15 DAP and 20 DAP respectively. Conserved miRNA families such as miR159, miR160, miR166, miR390, miR319, miR528 and miR529 were highly expressed in developing embryos; miR164, miR171, miR393 and miR2118 were highly expressed in developing endosperm. Genes targeted by those highly expressed miRNAs were found to be largely related to a regulation category, including the transcription, macromolecule biosynthetic and metabolic process in the embryo as well as the vitamin biosynthetic and metabolic process in the endosperm. Quantitative reverse transcription-PCR (qRT-PCR) analysis showed that these miRNAs displayed a negative correlation with the levels of their corresponding target genes. Importantly, our findings revealed that members of the miR169 family were highly and dynamically expressed in the developing kernel, which will help to exploit new players functioning in maize kernel development.

Alternative mechanisms for regulating racial responses according to internal vs external cues.

PubMed

Amodio, David M; Kubota, Jennifer T; Harmon-Jones, Eddie; Devine, Patricia G

2006-06-01

Personal (internal) and normative (external) impetuses for regulating racially biased behaviour are well-documented, yet the extent to which internally and externally driven regulatory processes arise from the same mechanism is unknown. Whereas the regulation of race bias according to internal cues has been associated with conflict-monitoring processes and activation of the dorsal anterior cingulate cortex (dACC), we proposed that responses regulated according to external cues to respond without prejudice involves mechanisms of error-perception, a process associated with rostral anterior cingulate cortex (rACC) activity. We recruited low-prejudice participants who reported high or low sensitivity to non-prejudiced norms, and participants completed a stereotype inhibition task in private or public while electroencephalography was recorded. Analysis of event-related potentials revealed that the error-related negativity component, linked to dACC activity, predicted behavioural control of bias across conditions, whereas the error-perception component, linked to rACC activity, predicted control only in public among participants sensitive to external pressures to respond without prejudice.

Statistical Analysis of the Processes Controlling Choline and Ethanolamine Glycerophospholipid Molecular Species Composition

PubMed Central

Kiebish, Michael A.; Yang, Kui; Han, Xianlin; Gross, Richard W.; Chuang, Jeffrey

2012-01-01

The regulation and maintenance of the cellular lipidome through biosynthetic, remodeling, and catabolic mechanisms are critical for biological homeostasis during development, health and disease. These complex mechanisms control the architectures of lipid molecular species, which have diverse yet highly regulated fatty acid chains at both the sn1 and sn2 positions. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) serve as the predominant biophysical scaffolds in membranes, acting as reservoirs for potent lipid signals and regulating numerous enzymatic processes. Here we report the first rigorous computational dissection of the mechanisms influencing PC and PE molecular architectures from high-throughput shotgun lipidomic data. Using novel statistical approaches, we have analyzed multidimensional mass spectrometry-based shotgun lipidomic data from developmental mouse heart and mature mouse heart, lung, brain, and liver tissues. We show that in PC and PE, sn1 and sn2 positions are largely independent, though for low abundance species regulatory processes may interact with both the sn1 and sn2 chain simultaneously, leading to cooperative effects. Chains with similar biochemical properties appear to be remodeled similarly. We also see that sn2 positions are more regulated than sn1, and that PC exhibits stronger cooperative effects than PE. A key aspect of our work is a novel statistically rigorous approach to determine cooperativity based on a modified Fisher's exact test using Markov Chain Monte Carlo sampling. This computational approach provides a novel tool for developing mechanistic insight into lipidomic regulation. PMID:22662143

Modulation of Food Reward by Endocrine and Environmental Factors: Update and Perspective.

PubMed

Figlewicz, Dianne P

2015-01-01

Palatable foods are frequently high in energy density. Chronic consumption of high-energy density foods can contribute to the development of cardiometabolic pathology including obesity, diabetes, and cardiovascular disease. This article reviews the contributions of extrinsic and intrinsic factors that influence the reward components of food intake. A narrative review was conducted to determine the behavioral and central nervous system (CNS) related processes involved in the reward components of high-energy density food intake. The rewarding aspects of food, particularly palatable and preferred foods, are regulated by CNS circuitry. Overlaying this regulation is modulation by intrinsic endocrine systems and metabolic hormones relating to energy homeostasis, developmental stage, or gender. It is now recognized that extrinsic or environmental factors, including ambient diet composition and the provocation of stress or anxiety, also contribute substantially to the expression of food reward behaviors such as motivation for, and seeking of, preferred foods. High-energy density food intake is influenced by both physiological and pathophysiological processes. Contextual, behavioral, and psychological factors and CNS-related processes represent potential targets for multiple types of therapeutic intervention.

Secretion and extracellular space travel of Wnt proteins.

PubMed

Gross, Julia Christina; Boutros, Michael

2013-08-01

Wnt signaling pathways control many processes during development, stem cell maintenance and homeostasis, and their aberrant regulation has been linked to diseases in man including diabetes, neurodegeneration and cancer. Wnts are hydrophobic proteins, however, quite paradoxically, they can travel over distances to induce cell-type specific responses. While there has been an initial focus on elucidating the intracellular signaling cascade, discoveries in the past few years have shed light on a highly complex, and regulated secretory process that guides Wnt proteins through the exocytic pathway. Wnt proteins are at least in portion packaged onto extracellular carriers such as exosomes. Similar to dysregulation of components in the Wnt receiving cell, failure to regulate Wnt secretion has been linked to cancer. Here, we review recent discoveries on factors and processes implicated in Wnt secretion. Copyright © 2013 Elsevier Ltd. All rights reserved.

RNA methylation in nuclear pre-mRNA processing.

PubMed

Covelo-Molares, Helena; Bartosovic, Marek; Vanacova, Stepanka

2018-06-19

Eukaryotic RNA can carry more than 100 different types of chemical modifications. Early studies have been focused on modifications of highly abundant RNA, such as ribosomal RNA and transfer RNA, but recent technical advances have made it possible to also study messenger RNA (mRNA). Subsequently, mRNA modifications, namely methylation, have emerged as key players in eukaryotic gene expression regulation. The most abundant and widely studied internal mRNA modification is N 6 -methyladenosine (m 6 A), but the list of mRNA chemical modifications continues to grow as fast as interest in this field. Over the past decade, transcriptome-wide studies combined with advanced biochemistry and the discovery of methylation writers, readers, and erasers revealed roles for mRNA methylation in the regulation of nearly every aspect of the mRNA life cycle and in diverse cellular, developmental, and disease processes. Although large parts of mRNA function are linked to its cytoplasmic stability and regulation of its translation, a number of studies have begun to provide evidence for methylation-regulated nuclear processes. In this review, we summarize the recent advances in RNA methylation research and highlight how these new findings have contributed to our understanding of methylation-dependent RNA processing in the nucleus. This article is categorized under: RNA Processing > RNA Editing and Modification RNA Processing > Splicing Regulation/Alternative Splicing RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications. © 2018 The Authors. WIREs RNA published by Wiley Periodicals, Inc.

Global insights into high temperature and drought stress regulated genes by RNA-Seq in economically important oilseed crop Brassica juncea.

PubMed

Bhardwaj, Ankur R; Joshi, Gopal; Kukreja, Bharti; Malik, Vidhi; Arora, Priyanka; Pandey, Ritu; Shukla, Rohit N; Bankar, Kiran G; Katiyar-Agarwal, Surekha; Goel, Shailendra; Jagannath, Arun; Kumar, Amar; Agarwal, Manu

2015-01-21

Brassica juncea var. Varuna is an economically important oilseed crop of family Brassicaceae which is vulnerable to abiotic stresses at specific stages in its life cycle. Till date no attempts have been made to elucidate genome-wide changes in its transcriptome against high temperature or drought stress. To gain global insights into genes, transcription factors and kinases regulated by these stresses and to explore information on coding transcripts that are associated with traits of agronomic importance, we utilized a combinatorial approach of next generation sequencing and de-novo assembly to discover B. juncea transcriptome associated with high temperature and drought stresses. We constructed and sequenced three transcriptome libraries namely Brassica control (BC), Brassica high temperature stress (BHS) and Brassica drought stress (BDS). More than 180 million purity filtered reads were generated which were processed through quality parameters and high quality reads were assembled de-novo using SOAPdenovo assembler. A total of 77750 unique transcripts were identified out of which 69,245 (89%) were annotated with high confidence. We established a subset of 19110 transcripts, which were differentially regulated by either high temperature and/or drought stress. Furthermore, 886 and 2834 transcripts that code for transcription factors and kinases, respectively, were also identified. Many of these were responsive to high temperature, drought or both stresses. Maximum number of up-regulated transcription factors in high temperature and drought stress belonged to heat shock factors (HSFs) and dehydration responsive element-binding (DREB) families, respectively. We also identified 239 metabolic pathways, which were perturbed during high temperature and drought treatments. Analysis of gene ontologies associated with differentially regulated genes forecasted their involvement in diverse biological processes. Our study provides first comprehensive discovery of B. juncea transcriptome under high temperature and drought stress conditions. Transcriptome resource generated in this study will enhance our understanding on the molecular mechanisms involved in defining the response of B. juncea against two important abiotic stresses. Furthermore this information would benefit designing of efficient crop improvement strategies for tolerance against conditions of high temperature regimes and water scarcity.

Mapping technological and biophysical capacities of watersheds to regulate floods

USGS Publications Warehouse

Mogollón, Beatriz; Villamagna, Amy M.; Frimpong, Emmanuel A.; Angermeier, Paul

2016-01-01

Flood regulation is a widely valued and studied service provided by watersheds. Flood regulation benefits people directly by decreasing the socio-economic costs of flooding and indirectly by its positive impacts on cultural (e.g., fishing) and provisioning (e.g., water supply) ecosystem services. Like other regulating ecosystem services (e.g., pollination, water purification), flood regulation is often enhanced or replaced by technology, but the relative efficacy of natural versus technological features in controlling floods has scarcely been examined. In an effort to assess flood regulation capacity for selected urban watersheds in the southeastern United States, we: (1) used long-term flood records to assess relative influence of technological and biophysical indicators on flood magnitude and duration, (2) compared the widely used runoff curve number (RCN) approach for assessing the biophysical capacity to regulate floods to an alternative approach that acknowledges land cover and soil properties separately, and (3) mapped technological and biophysical flood regulation capacities based on indicator importance-values derived for flood magnitude and duration. We found that watersheds with high biophysical (via the alternative approach) and technological capacities lengthened the duration and lowered the peak of floods. We found the RCN approach yielded results opposite that expected, possibly because it confounds soil and land cover processes, particularly in urban landscapes, while our alternative approach coherently separates these processes. Mapping biophysical (via the alternative approach) and technological capacities revealed great differences among watersheds. Our study improves on previous mapping of flood regulation by (1) incorporating technological capacity, (2) providing high spatial resolution (i.e., 10-m pixel) maps of watershed capacities, and (3) deriving importance-values for selected landscape indicators. By accounting for technology that enhances or replaces natural flood regulation, our approach enables watershed managers to make more informed choices in their flood-control investments.

Assembly of a Comprehensive Regulatory Network for the Mammalian Circadian Clock: A Bioinformatics Approach

PubMed Central

Lehmann, Robert; Abreu, Monica; Fuhr, Luise; Herzel, Hanspeter; Leser, Ulf; Relógio, Angela

2015-01-01

By regulating the timing of cellular processes, the circadian clock provides a way to adapt physiology and behaviour to the geophysical time. In mammals, a light-entrainable master clock located in the suprachiasmatic nucleus (SCN) controls peripheral clocks that are present in virtually every body cell. Defective circadian timing is associated with several pathologies such as cancer and metabolic and sleep disorders. To better understand the circadian regulation of cellular processes, we developed a bioinformatics pipeline encompassing the analysis of high-throughput data sets and the exploitation of published knowledge by text-mining. We identified 118 novel potential clock-regulated genes and integrated them into an existing high-quality circadian network, generating the to-date most comprehensive network of circadian regulated genes (NCRG). To validate particular elements in our network, we assessed publicly available ChIP-seq data for BMAL1, REV-ERBα/β and RORα/γ proteins and found strong evidence for circadian regulation of Elavl1, Nme1, Dhx6, Med1 and Rbbp7 all of which are involved in the regulation of tumourigenesis. Furthermore, we identified Ncl and Ddx6, as targets of RORγ and REV-ERBα, β, respectively. Most interestingly, these genes were also reported to be involved in miRNA regulation; in particular, NCL regulates several miRNAs, all involved in cancer aggressiveness. Thus, NCL represents a novel potential link via which the circadian clock, and specifically RORγ, regulates the expression of miRNAs, with particular consequences in breast cancer progression. Our findings bring us one step forward towards a mechanistic understanding of mammalian circadian regulation, and provide further evidence of the influence of circadian deregulation in cancer. PMID:25945798

High-throughput sequencing methods to study neuronal RNA-protein interactions.

PubMed

Ule, Jernej

2009-12-01

UV-cross-linking and RNase protection, combined with high-throughput sequencing, have provided global maps of RNA sites bound by individual proteins or ribosomes. Using a stringent purification protocol, UV-CLIP (UV-cross-linking and immunoprecipitation) was able to identify intronic and exonic sites bound by splicing regulators in mouse brain tissue. Ribosome profiling has been used to quantify ribosome density on budding yeast mRNAs under different environmental conditions. Post-transcriptional regulation in neurons requires high spatial and temporal precision, as is evident from the role of localized translational control in synaptic plasticity. It remains to be seen if the high-throughput methods can be applied quantitatively to study the dynamics of RNP (ribonucleoprotein) remodelling in specific neuronal populations during the neurodegenerative process. It is certain, however, that applications of new biochemical techniques followed by high-throughput sequencing will continue to provide important insights into the mechanisms of neuronal post-transcriptional regulation.

Deficits in Autonomic Indices of Emotion Regulation and Reward Processing Associated with Prescription Opioid Use and Misuse

PubMed Central

Garland, Eric L.; Bryan, Craig J.; Nakamura, Yoshio; Froeliger, Brett; Howard, Matthew O.

2016-01-01

Rationale Prescription opioid misuse and high dose opioid use may result in allostatic dysregulation of hedonic brain circuitry, leading to reduced emotion regulation capacity. In particular, opioid misuse may blunt the ability to experience and upregulate positive affect from natural rewards. Objectives The purpose of this study was to examine associations between opioid use/misuse and autonomic indices of emotion regulation capability in a sample of chronic pain patients receiving prescription opioid pharmacotherapy. Methods Chronic pain patients taking long-term opioid analgesics (N = 40) completed an emotion regulation task while heart rate variability (HRV) was recorded, as well as self-report measures of opioid misuse, craving, pain severity, and emotional distress. Based on a validated cut-point on the Current Opioid Misuse Measure, participants were grouped as opioid misusers or non-misusers. Opioid misuse status and morphine equivalent daily dose (MEDD) were examined as predictors of HRV and self-reports of emotion regulation. Results Opioid misusers exhibited significantly less HRV during positive and negative emotion regulation, and significantly less positive affect, than non-misusers, after controlling for confounders including pain severity and emotional distress. MEDD was inversely associated with positive emotion regulation efficacy. Conclusion Findings implicate the presence of reward processing deficits among chronic pain patients with opioid-misusing behaviors, and opioid dosage was associated with deficient emotion regulation, suggesting the presence of compromised top-down cognitive control over bottom-up hedonic processes. Emotion regulation among opioid misusers may represent an important treatment target. PMID:27933366

Differential gene expression at different stages of mesocarp development in high- and low-yielding oil palm.

PubMed

Wong, Yick Ching; Teh, Huey Fang; Mebus, Katharina; Ooi, Tony Eng Keong; Kwong, Qi Bin; Koo, Ka Loo; Ong, Chuang Kee; Mayes, Sean; Chew, Fook Tim; Appleton, David R; Kulaveerasingam, Harikrishna

2017-06-21

The oil yield trait of oil palm is expected to involve multiple genes, environmental influences and interactions. Many of the underlying mechanisms that contribute to oil yield are still poorly understood. In this study, we used a microarray approach to study the gene expression profiles of mesocarp tissue at different developmental stages, comparing genetically related high- and low- oil yielding palms to identify genes that contributed to the higher oil-yielding palm and might contribute to the wider genetic improvement of oil palm breeding populations. A total of 3412 (2001 annotated) gene candidates were found to be significantly differentially expressed between high- and low-yielding palms at at least one of the different stages of mesocarp development evaluated. Gene Ontologies (GO) enrichment analysis identified 28 significantly enriched GO terms, including regulation of transcription, fatty acid biosynthesis and metabolic processes. These differentially expressed genes comprise several transcription factors, such as, bHLH, Dof zinc finger proteins and MADS box proteins. Several genes involved in glycolysis, TCA, and fatty acid biosynthesis pathways were also found up-regulated in high-yielding oil palm, among them; pyruvate dehydrogenase E1 component Subunit Beta (PDH), ATP-citrate lyase, β- ketoacyl-ACP synthases I (KAS I), β- ketoacyl-ACP synthases III (KAS III) and ketoacyl-ACP reductase (KAR). Sucrose metabolism-related genes such as Invertase, Sucrose Synthase 2 and Sucrose Phosphatase 2 were found to be down-regulated in high-yielding oil palms, compared to the lower yield palms. Our findings indicate that a higher carbon flux (channeled through down-regulation of the Sucrose Synthase 2 pathway) was being utilized by up-regulated genes involved in glycolysis, TCA and fatty acid biosynthesis leading to enhanced oil production in the high-yielding oil palm. These findings are an important stepping stone to understand the processes that lead to production of high-yielding oil palms and have implications for breeding to maximize oil production.

No Special K! A Signal Detection Framework for the Strategic Regulation of Memory Accuracy

ERIC Educational Resources Information Center

Higham, Philip A.

2007-01-01

Two experiments investigated criterion setting and metacognitive processes underlying the strategic regulation of accuracy on the Scholastic Aptitude Test (SAT) using Type-2 signal detection theory (SDT). In Experiment 1, report bias was manipulated by penalizing participants either 0.25 (low incentive) or 4 (high incentive) points for each error.…

[Early mother-infant interaction and factors negatively affecting parenting].

PubMed

Cerezo, María Angeles; Trenado, Rosa María; Pons-Salvador, Gemma

2006-08-01

The social information-processing model contributes to identifying the psychological processes underlying the construct "sensitivity" in early mother-child interaction. Negative emotional states associated with inadequate self-regulation in coping with stressors affect the mother's attention skills and the processing of the baby's signals. This leads to less synchronous parental practices, particularly unsatisfactory when the baby is unhappy, or crying because the required self-regulation is not provided. This micro-social research studies the sequential profile of maternal reactions to the baby's positive/neutral vs. difficult behaviours and compares them in two groups of dyads, one with mothers who reported high levels of distress and other negative factors for parenting and another group with low levels. The unfavourable circumstances of the high stress group and their negative effects on interaction were observed in some indiscriminate maternal responses and particularly as they reacted to their baby's difficult behaviour, when the mother's regulatory role is more necessary.

Dynamic integration of splicing within gene regulatory pathways

PubMed Central

Braunschweig, Ulrich; Gueroussov, Serge; Plocik, Alex; Graveley, Brenton R.; Blencowe, Benjamin J.

2013-01-01

Precursor mRNA splicing is one of the most highly regulated processes in metazoan species. In addition to generating vast repertoires of RNAs and proteins, splicing has a profound impact on other gene regulatory layers, including mRNA transcription, turnover, transport and translation. Conversely, factors regulating chromatin and transcription complexes impact the splicing process. This extensive cross-talk between gene regulatory layers takes advantage of dynamic spatial, physical and temporal organizational properties of the cell nucleus, and further emphasizes the importance of developing a multidimensional understanding of splicing control. PMID:23498935

Comparative Transcriptomes Analysis of Red- and White-Fleshed Apples in an F1 Population of Malus sieversii f. niedzwetzkyana Crossed with M. domestica ‘Fuji’

PubMed Central

Wang, Nan; Zheng, Yi; Duan, Naibin; Zhang, Zongying; Ji, Xiaohao; Jiang, Shenghui; Sun, Shasha; Yang, Long; Bai, Yang; Fei, Zhangjun; Chen, Xuesen

2015-01-01

Transcriptome profiles of the red- and white-fleshed apples in an F1 segregating population of Malus sieversii f.Niedzwetzkyana and M.domestica ‘Fuji’ were generated using the next-generation high-throughput RNA sequencing (RNA-Seq) technology and compared. A total of 114 differentially expressed genes (DEGs) were obtained, of which 88 were up-regulated and 26 were down-regulated in red-fleshed apples. The 88 up-regulated genes were enriched with those related to flavonoid biosynthetic process and stress responses. Further analysis identified 22 genes associated with flavonoid biosynthetic process and 68 genes that may be related to stress responses. Furthermore, the expression of 20 up-regulated candidate genes (10 related to flavonoid biosynthesis, two encoding MYB transcription factors and eight related to stress responses) and 10 down-regulated genes were validated by quantitative real-time PCR. After exploring the possible regulatory network, we speculated that flavonoid metabolism might be involved in stress responses in red-fleshed apple. Our findings provide a theoretical basis for further enriching gene resources associated with flavonoid synthesis and stress responses of fruit trees and for breeding elite apples with high flavonoid content and/or increased stress tolerances. PMID:26207813

Comparative Transcriptomes Analysis of Red- and White-Fleshed Apples in an F1 Population of Malus sieversii f. niedzwetzkyana Crossed with M. domestica 'Fuji'.

PubMed

Wang, Nan; Zheng, Yi; Duan, Naibin; Zhang, Zongying; Ji, Xiaohao; Jiang, Shenghui; Sun, Shasha; Yang, Long; Bai, Yang; Fei, Zhangjun; Chen, Xuesen

2015-01-01

Transcriptome profiles of the red- and white-fleshed apples in an F1 segregating population of Malus sieversii f.Niedzwetzkyana and M.domestica 'Fuji' were generated using the next-generation high-throughput RNA sequencing (RNA-Seq) technology and compared. A total of 114 differentially expressed genes (DEGs) were obtained, of which 88 were up-regulated and 26 were down-regulated in red-fleshed apples. The 88 up-regulated genes were enriched with those related to flavonoid biosynthetic process and stress responses. Further analysis identified 22 genes associated with flavonoid biosynthetic process and 68 genes that may be related to stress responses. Furthermore, the expression of 20 up-regulated candidate genes (10 related to flavonoid biosynthesis, two encoding MYB transcription factors and eight related to stress responses) and 10 down-regulated genes were validated by quantitative real-time PCR. After exploring the possible regulatory network, we speculated that flavonoid metabolism might be involved in stress responses in red-fleshed apple. Our findings provide a theoretical basis for further enriching gene resources associated with flavonoid synthesis and stress responses of fruit trees and for breeding elite apples with high flavonoid content and/or increased stress tolerances.

FY is an RNA 3' end-processing factor that interacts with FCA to control the Arabidopsis floral transition.

PubMed

Simpson, Gordon G; Dijkwel, Paul P; Quesada, Victor; Henderson, Ian; Dean, Caroline

2003-06-13

The nuclear RNA binding protein, FCA, promotes Arabidopsis reproductive development. FCA contains a WW protein interaction domain that is essential for FCA function. We have identified FY as a protein partner for this domain. FY belongs to a highly conserved group of eukaryotic proteins represented in Saccharomyces cerevisiae by the RNA 3' end-processing factor, Pfs2p. FY regulates RNA 3' end processing in Arabidopsis as evidenced through its role in FCA regulation. FCA expression is autoregulated through the use of different polyadenylation sites within the FCA pre-mRNA, and the FCA/FY interaction is required for efficient selection of the promoter-proximal polyadenylation site. The FCA/FY interaction is also required for the downregulation of the floral repressor FLC. We propose that FCA controls 3' end formation of specific transcripts and that in higher eukaryotes, proteins homologous to FY may have evolved as sites of association for regulators of RNA 3' end processing.

Translation regulation in plants: an interesting past, an exciting present and a promising future.

PubMed

Merchante, Catharina; Stepanova, Anna N; Alonso, Jose M

2017-05-01

Changes in gene expression are at the core of most biological processes, from cell differentiation to organ development, including the adaptation of the whole organism to the ever-changing environment. Although the central role of transcriptional regulation is solidly established and the general mechanisms involved in this type of regulation are relatively well understood, it is clear that regulation at a translational level also plays an essential role in modulating gene expression. Despite the large number of examples illustrating the critical role played by translational regulation in determining the expression levels of a gene, our understanding of the molecular mechanisms behind such types of regulation has been slow to emerge. With the recent development of high-throughput approaches to map and quantify different critical parameters affecting translation, such as RNA structure, protein-RNA interactions and ribosome occupancy at the genome level, a renewed enthusiasm toward studying translation regulation is warranted. The use of these new powerful technologies in well-established and uncharacterized translation-dependent processes holds the promise to decipher the likely complex and diverse, but also fascinating, mechanisms behind the regulation of translation. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

A brain-computer interface based on self-regulation of gamma-oscillations in the superior parietal cortex

NASA Astrophysics Data System (ADS)

Grosse-Wentrup, Moritz; Schölkopf, Bernhard

2014-10-01

Objective. Brain-computer interface (BCI) systems are often based on motor- and/or sensory processes that are known to be impaired in late stages of amyotrophic lateral sclerosis (ALS). We propose a novel BCI designed for patients in late stages of ALS that only requires high-level cognitive processes to transmit information from the user to the BCI. Approach. We trained subjects via EEG-based neurofeedback to self-regulate the amplitude of gamma-oscillations in the superior parietal cortex (SPC). We argue that parietal gamma-oscillations are likely to be associated with high-level attentional processes, thereby providing a communication channel that does not rely on the integrity of sensory- and/or motor-pathways impaired in late stages of ALS. Main results. Healthy subjects quickly learned to self-regulate gamma-power in the SPC by alternating between states of focused attention and relaxed wakefulness, resulting in an average decoding accuracy of 70.2%. One locked-in ALS patient (ALS-FRS-R score of zero) achieved an average decoding accuracy significantly above chance-level though insufficient for communication (55.8%). Significance. Self-regulation of gamma-power in the SPC is a feasible paradigm for brain-computer interfacing and may be preserved in late stages of ALS. This provides a novel approach to testing whether completely locked-in ALS patients retain the capacity for goal-directed thinking.

A novel RNA species from the turtle mitochondrial genome: induction and regulation of transcription and processing under anoxic and freezing stresses.

PubMed

Cai, Q; Storey, K B

1997-08-01

The present study identifies a previously cloned cDNA, pBTaR914, as homologous to the mitochondrial WANCY (tryptophan, alanine, asparagine, cysteine, and tyrosine) tRNA gene cluster. This cDNA clone has a 304-bp sequence and its homologue, pBTaR09, has a 158-bp sequence with a long poly(A)+ tail (more than 60 adenosines). RNA blotting analysis using pBTaR914 probe against the total RNA from the tissues of adult and hatchling turtles revealed five bands: 540, 1800, 2200, 3200, and 3900 nucleotides (nt). The 540-nt transcript is considered to be an intact mtRNA unit from a novel mtDNA gene designated WANCYHP that overlaps the WANCY tRNA gene cluster region. This transcript was highly induced by both anoxic and freezing stresses in turtle heart. The other transcripts are considered to be the processed intermediates of mtRNA transcripts with WANCYHP sequence. All these transcripts were differentially regulated by anoxia and freezing in different organs. The data suggest that mtRNA processing is sensitive to regulation by external stresses, oxygen deprivation, and freezing. Furthermore, the fact that the WANCYHP transcript is highly induced during anoxic exposure suggests that it may play an important role in the regulation of mitochondrial activities to coordinate the physiological adaptation to anoxia.

Salicylic acid and nitric oxide alleviate high temperature induced oxidative damage in Lablab purpureus L plants by regulating bio-physical processes and DNA methylation.

PubMed

Rai, Krishna Kumar; Rai, Nagendra; Rai, Shashi Pandey

2018-07-01

Salicylic acid (SA) and sodium nitroprusside (SNP, NO donor) modulates plant growth and development processes and recent findings have also revealed their involvement in the regulation of epigenetic factors under stress condition. In the present study, some of these factors were comparatively studied in hyacinth bean plants subjected to high temperature (HT) environment (40-42 °C) with and without exogenous application of SA and SNP under field condition. Exogenous application of SA and SNP substantially modulated the growth and biophysical process of hyacinth bean plants under HT environment. Exogenous application of SA and SNP also remarkably regulated the activities of antioxidant enzymes, modulated mRNA level of certain enzymes, improves plant water relation, enhance photosynthesis and thereby increasing plant defence under HT. Coupled restriction enzyme digestion-random amplification (CRED-RA) technique revealed that many methylation changes were "dose dependent" and HT significantly increased DNA damages as evidenced by both increase and decrease in bands profiles, methylation and de-methylation pattern. Thus, the result of the present study clearly shows that exogenous SA and SNP regulates DNA methylation pattern, modulates stress-responsive genes and can impart transient HT tolerance by synchronizing growth and physiological acclimatization of plants, thus narrowing the gaps between physio-biochemical and molecular events in addressing HT tolerance. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Three Pairs of Protease-Serpin Complexes Cooperatively Regulate the Insect Innate Immune Responses*

PubMed Central

Jiang, Rui; Kim, Eun-Hye; Gong, Ji-Hee; Kwon, Hyun-Mi; Kim, Chan-Hee; Ryu, Kyoung-Hwa; Park, Ji-Won; Kurokawa, Kenji; Zhang, Jinghai; Gubb, David; Lee, Bok-Luel

2009-01-01

Serpins are known to be necessary for the regulation of several serine protease cascades. However, the mechanisms of how serpins regulate the innate immune responses of invertebrates are not well understood due to the uncertainty of the identity of the serine proteases targeted by the serpins. We recently reported the molecular activation mechanisms of three serine protease-mediated Toll and melanin synthesis cascades in a large beetle, Tenebrio molitor. Here, we purified three novel serpins (SPN40, SPN55, and SPN48) from the hemolymph of T. molitor. These serpins made specific serpin-serine protease pairs with three Toll cascade-activating serine proteases, such as modular serine protease, Spätzle-processing enzyme-activating enzyme, and Spätzle-processing enzyme and cooperatively blocked the Toll signaling cascade and β-1,3-glucan-mediated melanin biosynthesis. Also, the levels of SPN40 and SPN55 were dramatically increased in vivo by the injection of a Toll ligand, processed Spätzle, into Tenebrio larvae. This increase in SPN40 and SPN55 levels indicates that these serpins function as inducible negative feedback inhibitors. Unexpectedly, SPN55 and SPN48 were cleaved at Tyr and Glu residues in reactive center loops, respectively, despite being targeted by trypsin-like Spätzle-processing enzyme-activating enzyme and Spätzle-processing enzyme. These cleavage patterns are also highly similar to those of unusual mammalian serpins involved in blood coagulation and blood pressure regulation, and they may contribute to highly specific and timely inactivation of detrimental serine proteases during innate immune responses. Taken together, these results demonstrate the specific regulatory evidences of innate immune responses by three novel serpins. PMID:19858208

The Role of Individual and Collective Mindfulness in Promoting Occupational Safety in Health Care.

PubMed

Dierynck, Bart; Leroy, Hannes; Savage, Grant T; Choi, Ellen

2017-02-01

Although the importance of safety regulations is highly emphasized in hospitals, nurses frequently work around, or intentionally bypass, safety regulations. We argue that work-arounds occur because adhering to safety regulations usually requires more time and work process design often lacks complementarity with safety regulations. Our main proposition is that mindfulness is associated with a decrease in occupational safety failures through a decrease in work-arounds. First, we propose that individual mindfulness may prevent the depletion of motivational resources caused by worrying about the consequences of time lost when adhering to safety regulations. Second, we argue that collective mindfulness may provide nursing teams with a cognitive infrastructure that facilitates the detection and adaptation of work processes. The results of a multilevel analysis of 580 survey responses from nurses are consistent with our propositions. Our multilevel analytic approach enables us to account for the unique variance in work-arounds that individual and collective mindfulness explain.

Neural processing of emotional-intensity predicts emotion regulation choice.

PubMed

Shafir, Roni; Thiruchselvam, Ravi; Suri, Gaurav; Gross, James J; Sheppes, Gal

2016-12-01

Emotional-intensity is a core characteristic of affective events that strongly determines how individuals choose to regulate their emotions. Our conceptual framework suggests that in high emotional-intensity situations, individuals prefer to disengage attention using distraction, which can more effectively block highly potent emotional information, as compared with engagement reappraisal, which is preferred in low emotional-intensity. However, existing supporting evidence remains indirect because prior intensity categorization of emotional stimuli was based on subjective measures that are potentially biased and only represent the endpoint of emotional-intensity processing. Accordingly, this study provides the first direct evidence for the role of online emotional-intensity processing in predicting behavioral regulatory-choices. Utilizing the high temporal resolution of event-related potentials, we evaluated online neural processing of stimuli's emotional-intensity (late positive potential, LPP) prior to regulatory-choices between distraction and reappraisal. Results showed that enhanced neural processing of intensity (enhanced LPP amplitudes) uniquely predicted (above subjective measures of intensity) increased tendency to subsequently choose distraction over reappraisal. Additionally, regulatory-choices led to adaptive consequences, demonstrated in finding that actual implementation of distraction relative to reappraisal-choice resulted in stronger attenuation of LPPs and self-reported arousal. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Self-regulation of brain rhythms in the precuneus: a novel BCI paradigm for patients with ALS

NASA Astrophysics Data System (ADS)

Fomina, Tatiana; Lohmann, Gabriele; Erb, Michael; Ethofer, Thomas; Schölkopf, Bernhard; Grosse-Wentrup, Moritz

2016-12-01

Objective. Electroencephalographic (EEG) brain-computer interfaces (BCIs) hold promise in restoring communication for patients with completely locked-in stage amyotrophic lateral sclerosis (ALS). However, these patients cannot use existing EEG-based BCIs, arguably because such systems rely on brain processes that are impaired in the late stages of ALS. In this work, we introduce a novel BCI designed for patients in late stages of ALS based on high-level cognitive processes that are less likely to be affected by ALS. Approach. We trained two ALS patients via EEG-based neurofeedback to use self-regulation of theta or gamma oscillations in the precuneus for basic communication. Because there is a tight connection between the precuneus and consciousness, precuneus oscillations are arguably generated by high-level cognitive processes, which are less likely to be affected by ALS than processes linked to the peripheral nervous system. Main results. Both patients learned to self-regulate their precuneus oscillations and achieved stable online decoding accuracy over the course of disease progression. One patient achieved a mean online decoding accuracy in a binary decision task of 70.55% across 26 training sessions, and the other patient achieved 59.44% across 16 training sessions. We provide empirical evidence that these oscillations were cortical in nature and originated from the intersection of the precuneus, cuneus, and posterior cingulate. Significance. Our results establish that ALS patients can employ self-regulation of precuneus oscillations for communication. Such a BCI is likely to be available to ALS patients as long as their consciousness supports communication.

Compliance with High-Intensity Radiated Fields Regulations - Emitter's Perspective

NASA Technical Reports Server (NTRS)

Statman, Joseph; Jamnejad, Vahraz; Nguyen, Lee

2012-01-01

NASA's Deep Space Network (DSN) uses high-power transmitters on its large antennas to communicate with spacecraft of NASA and its partner agencies. The prime reflectors of the DSN antennas are parabolic, at 34m and 70m in diameter. The DSN transmitters radiate Continuous Wave (CW) signals at 20 kW - 500 kW at X-band and S-band frequencies. The combination of antenna reflector size and high frequency results in a very narrow beam with extensive oscillating near-field pattern. Another unique feature of the DSN antennas is that they (and the radiated beam) move mostly at very slow sidereal rate, essentially identical in magnitude and at the opposite direction of Earth rotation.The DSN is in the process of revamping its documentation to provide analysis of the High Intensity Radiation Fields (HIRF) environment resulting from radio frequency radiation from DSN antennas for comparison to FAA regulations regarding certification of HIRF protection as outlined in the FAA regulations on HIRF protection for aircraft electrical and electronic systems (Title 14, Code of Federal Regulations (14 CFR) [section sign][section sign] 23.1308, 25.1317, 27.1317, and 29.1317).This paper presents work done at JPL, in consultation with the FAA. The work includes analysis of the radiated field structure created by the unique DSN emitters (combination of transmitters and antennas) and comparing it to the fields defined in the environments in the FAA regulations. The paper identifies areas that required special attention, including the implications of the very narrow beam of the DSN emitters and the sidereal rate motion. The paper derives the maximum emitter power allowed without mitigation and the mitigation zones, where required.Finally, the paper presents summary of the results of the analyses of the DSN emitters and the resulting DSN process documentation.

Roles of P21-activated kinases and associated proteins in epithelial wound healing.

PubMed

Zegers, Mirjam

2008-01-01

The primary function of epithelia is to provide a barrier between the extracellular environment and the interior of the body. Efficient epithelial repair mechanisms are therefore crucial for homeostasis. The epithelial wound-healing process involves highly regulated morphogenetic changes of epithelial cells that are driven by dynamic changes of the cytoskeleton. P21-activated kinases are serine/threonine kinases that have emerged as important regulators of the cytoskeleton. These kinases, which are activated downsteam of the Rho GTPases Rac and cd42, were initially mostly implicated in the regulation of cell migration. More recently, however, these kinases were shown to have many additional functions that are relevant to the regulation of epithelial wound healing. Here, we provide an overview of the morphogenetic changes of epithelial cells during wound healing and the many functions of p21-activated kinases in these processes.

DNA replication components as regulators of epigenetic inheritance--lesson from fission yeast centromere.

PubMed

He, Haijin; Gonzalez, Marlyn; Zhang, Fan; Li, Fei

2014-06-01

Genetic information stored in DNA is accurately copied and transferred to subsequent generations through DNA replication. This process is accomplished through the concerted actions of highly conserved DNA replication components. Epigenetic information stored in the form of histone modifications and DNA methylation, constitutes a second layer of regulatory information important for many cellular processes, such as gene expression regulation, chromatin organization, and genome stability. During DNA replication, epigenetic information must also be faithfully transmitted to subsequent generations. How this monumental task is achieved remains poorly understood. In this review, we will discuss recent advances on the role of DNA replication components in the inheritance of epigenetic marks, with a particular focus on epigenetic regulation in fission yeast. Based on these findings, we propose that specific DNA replication components function as key regulators in the replication of epigenetic information across the genome.

Kinesin regulation dynamics through cargo delivery, a single molecule investigation

NASA Astrophysics Data System (ADS)

Kovacs, Anthony; Kessler, Jonathan; Lin, Huawen; Dutcher, Susan; Wang, Yan Mei

2015-03-01

Kinesins are microtubule-based motors that deliver cargo to their destinations in a highly regulated manner. Although in recent years numerous regulators of cargo delivery have been identified, the regulation mechanism of kinesin through the cargo delivery and recycling process is not known. By performing single molecule fluorescence imaging measurements in Chlamydomonas flagella, which are 200 nm in diameter, 10 microns in length, and contain 9 sets of microtubule doublets, we tracked the intraflagellar transport (IFT) trains, BBSome cargo, and kinesin-2 motors through the cargo delivery process and determined the aforementioned dynamics. Upon arrival at the microtubule plus end at the flagellar tip, (1) IFT trains and BBSome cargo remain intact, dissociate together from kinesins and microtubules, and diffuse along flagellar membrane for a mean of 2.3 sec before commencing retrograde travel. (2) Kinesin motors remain bound to and diffuse along microtubules for 1.3 sec before dissociating into the flagellar lumen for recycling.

Context-Sensitive Adjustment of Cognitive Control in Dual-Task Performance

ERIC Educational Resources Information Center

Fischer, Rico; Gottschalk, Caroline; Dreisbach, Gesine

2014-01-01

Performing 2 highly similar tasks at the same time requires an adaptive regulation of cognitive control to shield prioritized primary task processing from between-task (cross-talk) interference caused by secondary task processing. In the present study, the authors investigated how implicitly and explicitly delivered information promotes the…

Atypical chemokine receptor ACKR2 controls branching morphogenesis in the developing mammary gland

PubMed Central

Hewit, Kay D.; Pallas, Kenneth J.; Cairney, Claire J.; Lee, Kit M.; Hansell, Christopher A.; Stein, Torsten

2017-01-01

Macrophages are important regulators of branching morphogenesis during development and postnatally in the mammary gland. Regulation of macrophage dynamics during these processes can therefore have a profound impact on development. We demonstrate here that the developing mammary gland expresses high levels of inflammatory CC-chemokines, which are essential in vivo regulators of macrophage migration. We further demonstrate that the atypical chemokine receptor ACKR2, which scavenges inflammatory CC-chemokines, is differentially expressed during mammary gland development. We have previously shown that ACKR2 regulates macrophage dynamics during lymphatic vessel development. Here, we extend these observations to reveal a novel role for ACKR2 in regulating the postnatal development of the mammary gland. Specifically, we show that Ackr2−/− mice display precocious mammary gland development. This is associated with increased macrophage recruitment to the developing gland and increased density of the ductal epithelial network. These data demonstrate that ACKR2 is an important regulator of branching morphogenesis in diverse biological contexts and provide the first evidence of a role for chemokines and their receptors in postnatal development processes. PMID:27888192

Social Justice and Job Distribution in Japan: Class, Minority and Gender.

ERIC Educational Resources Information Center

Okano, Kaori H.

2000-01-01

Provides a brief overview of Japanese high school students in terms of 1995 post-school destinations and types of jobs obtained. Describes the school-based job referral process that systematically regulates job distribution for high school graduates, including high school-employer networks and guidance for students in employment-related…

Individual differences in automatic emotion regulation affect the asymmetry of the LPP component.

PubMed

Zhang, Jing; Zhou, Renlai

2014-01-01

The main goal of this study was to investigate how automatic emotion regulation altered the hemispheric asymmetry of ERPs elicited by emotion processing. We examined the effect of individual differences in automatic emotion regulation on the late positive potential (LPP) when participants were viewing blocks of positive high arousal, positive low arousal, negative high arousal and negative low arousal pictures from International affect picture system (IAPS). Two participant groups were categorized by the Emotion Regulation-Implicit Association Test which has been used in previous research to identify two groups of participants with automatic emotion control and with automatic emotion express. The main finding was that automatic emotion express group showed a right dominance of the LPP component at posterior electrodes, especially in high arousal conditions. But no right dominance of the LPP component was observed for automatic emotion control group. We also found the group with automatic emotion control showed no differences in the right posterior LPP amplitude between high- and low-arousal emotion conditions, while the participants with automatic emotion express showed larger LPP amplitude in the right posterior in high-arousal conditions compared to low-arousal conditions. This result suggested that AER (Automatic emotion regulation) modulated the hemispheric asymmetry of LPP on posterior electrodes and supported the right hemisphere hypothesis.

Transcriptome Analysis of Al-Induced Genes in Buckwheat (Fagopyrum esculentum Moench) Root Apex: New Insight into Al Toxicity and Resistance Mechanisms in an Al Accumulating Species.

PubMed

Xu, Jia Meng; Fan, Wei; Jin, Jian Feng; Lou, He Qiang; Chen, Wei Wei; Yang, Jian Li; Zheng, Shao Jian

2017-01-01

Relying on Al-activated root oxalate secretion, and internal detoxification and accumulation of Al, buckwheat is highly Al resistant. However, the molecular mechanisms responsible for these processes are still poorly understood. It is well-known that root apex is the critical region of Al toxicity that rapidly impairs a series of events, thus, resulting in inhibition of root elongation. Here, we carried out transcriptome analysis of the buckwheat root apex (0-1 cm) with regards to early response (first 6 h) to Al stress (20 μM), which is crucial for identification of both genes and processes involved in Al toxicity and tolerance mechanisms. We obtained 34,469 unigenes with 26,664 unigenes annotated in the NCBI database, and identified 589 up-regulated and 255 down-regulated differentially expressed genes (DEGs) under Al stress. Functional category analysis revealed that biological processes differ between up- and down-regulated genes, although 'metabolic processes' were the most affected category in both up- and down-regulated DEGs. Based on the data, it is proposed that Al stress affects a variety of biological processes that collectively contributes to the inhibition of root elongation. We identified 30 transporter genes and 27 transcription factor (TF) genes induced by Al. Gene homology analysis highlighted candidate genes encoding transporters associated with Al uptake, transport, detoxification, and accumulation. We also found that TFs play critical role in transcriptional regulation of Al resistance genes in buckwheat. In addition, gene duplication events are very common in the buckwheat genome, suggesting a possible role for gene duplication in the species' high Al resistance. Taken together, the transcriptomic analysis of buckwheat root apex shed light on the processes that contribute to the inhibition of root elongation. Furthermore, the comprehensive analysis of both transporter genes and TF genes not only deep our understanding on the responses of buckwheat roots to Al toxicity but provide a good start for functional characterization of genes critical for Al tolerance.

Gene expression profile change and growth inhibition in Drosophila larvae treated with azadirachtin.

PubMed

Lai, Duo; Jin, Xiaoyong; Wang, Hao; Yuan, Mei; Xu, Hanhong

2014-09-20

Azadirachtin is a botanical insecticide that affects various biological processes. The effects of azadirachtin on the digital gene expression profile and growth inhibition in Drosophila larvae have not been investigated. In this study, we applied high-throughput sequencing technology to detect the differentially expressed genes of Drosophila larvae regulated by azadirachtin. A total of 15,322 genes were detected, and 28 genes were found to be significantly regulated by azadirachtin. Biological process and pathway analysis showed that azadirachtin affected starch and sucrose metabolism, defense response, signal transduction, instar larval or pupal development, and chemosensory behavior processes. The genes regulated by azadirachtin were mainly enriched in starch and sucrose metabolism. This study provided a general digital gene expression profile of dysregulated genes in response to azadirachtin and showed that azadirachtin provoked potent growth inhibitory effects in Drosophila larvae by regulating the genes of cuticular protein, amylase, and odorant-binding protein. Finally, we propose a potential mechanism underlying the dysregulation of the insulin/insulin-like growth factor signaling pathway by azadirachtin. Copyright © 2014 Elsevier B.V. All rights reserved.

Mothering, fathering, and the regulation of negative and positive emotions in high-functioning preschoolers with autism spectrum disorder.

PubMed

Hirschler-Guttenberg, Yael; Golan, Ofer; Ostfeld-Etzion, Sharon; Feldman, Ruth

2015-05-01

Children with autism spectrum disorder (ASD) exhibit difficulties in regulating emotions and authors have called to study the specific processes underpinning emotion regulation (ER) in ASD. Yet, little observational research examined the strategies preschoolers with ASD use to regulate negative and positive emotions in the presence of their mothers and fathers. Forty preschoolers with ASD and 40 matched typically developing children and their mothers and fathers participated. Families were visited twice for identical battery of paradigms with mother or father. Parent-child interactions were coded for parent and child behaviors and children engaged in ER paradigms eliciting negative (fear) and positive (joy) emotions with each parent. ER paradigms were microcoded for negative and positive emotionality, ER strategies, and parent regulation facilitation. During free play, mothers' and fathers' sensitivity and warm discipline were comparable across groups; however, children with ASD displayed lower positive engagement and higher withdrawal. During ER paradigms, children with ASD expressed less positive emotionality overall and more negative emotionality during fear with father. Children with ASD used more simple self-regulatory strategies, particularly during fear, but expressed comparable levels of assistance seeking behavior toward mother and father in negative and positive contexts. Parents of children with ASD used less complex regulation facilitation strategies, including cognitive reappraisal and emotional reframing, and employed simple tactics, such as physical comforting to manage fear and social gaze to maintain joy. Findings describe general and parent- and emotion-specific processes of child ER and parent regulation facilitation in preschoolers with ASD. Results underscore the ability of such children to seek parental assistance during moments of high arousal and the parents' sensitive adaptation to their children's needs. Reduced positive emotionality, rather than increased negative reactivity and self-regulatory efforts, emerges as the consistent element associated with ER processes in this group. © 2014 Association for Child and Adolescent Mental Health.

The Cognitive Building Blocks of Emotion Regulation: Ability to Update Working Memory Moderates the Efficacy of Rumination and Reappraisal on Emotion

PubMed Central

Pe, Madeline Lee; Raes, Filip; Kuppens, Peter

2013-01-01

The ability to regulate emotions is a critical component of healthy emotional functioning. Therefore, it is important to determine factors that contribute to the efficacy of emotion regulation. The present article examined whether the ability to update emotional information in working memory is a predictor of the efficacy of rumination and reappraisal on affective experience both at the trait level (Study 1) and in daily life (Study 2). In both studies, results revealed that the relationship between use of reappraisal and high arousal negative emotions was moderated by updating ability. Specifically, use of reappraisal was associated with decreased high arousal negative emotions for participants with high updating ability, while no significant relationship was found for those with low updating ability. In addition, both studies also revealed that the relationship between rumination and high arousal negative emotions was moderated by updating ability. In general, use of rumination was associated with elevated high arousal negative emotions. However, this relationship was blunted for participants with high updating ability. That is, use of rumination was associated with less elevated high arousal negative emotions for participants with high updating ability. These results identify the ability to update emotional information in working memory as a crucial process modulating the efficacy of emotion regulation efforts. PMID:23874872

The cognitive building blocks of emotion regulation: ability to update working memory moderates the efficacy of rumination and reappraisal on emotion.

PubMed

Pe, Madeline Lee; Raes, Filip; Kuppens, Peter

2013-01-01

The ability to regulate emotions is a critical component of healthy emotional functioning. Therefore, it is important to determine factors that contribute to the efficacy of emotion regulation. The present article examined whether the ability to update emotional information in working memory is a predictor of the efficacy of rumination and reappraisal on affective experience both at the trait level (Study 1) and in daily life (Study 2). In both studies, results revealed that the relationship between use of reappraisal and high arousal negative emotions was moderated by updating ability. Specifically, use of reappraisal was associated with decreased high arousal negative emotions for participants with high updating ability, while no significant relationship was found for those with low updating ability. In addition, both studies also revealed that the relationship between rumination and high arousal negative emotions was moderated by updating ability. In general, use of rumination was associated with elevated high arousal negative emotions. However, this relationship was blunted for participants with high updating ability. That is, use of rumination was associated with less elevated high arousal negative emotions for participants with high updating ability. These results identify the ability to update emotional information in working memory as a crucial process modulating the efficacy of emotion regulation efforts.

Identification and function of proteolysis regulators in seminal fluid.

PubMed

Laflamme, Brooke A; Wolfner, Mariana F

2013-02-01

Proteins in the seminal fluid of animals with internal fertilization effect numerous responses in mated females that impact both male and female fertility. Among these proteins is the highly represented class of proteolysis regulators (proteases and their inhibitors). Though proteolysis regulators have now been identified in the seminal fluid of all animals in which proteomic studies of the seminal fluid have been conducted (as well as several other species in which they have not), a unified understanding of the importance of proteolysis to male fertilization success and other reproductive processes has not yet been achieved. In this review, we provide an overview of the identification of proteolysis regulators in the seminal fluid of humans and Drosophila melanogaster, the two species with the most comprehensively known seminal fluid proteomes. We also highlight reports demonstrating the functional significance of specific proteolysis regulators in reproductive and post-mating processes. Finally, we make broad suggestions for the direction of future research into the roles of both active seminal fluid proteolysis regulators and their inactive homologs, another significant class of seminal fluid proteins. We hope that this review aids researchers in pursuing a coordinated study of the functional significance of proteolysis regulators in semen. Copyright © 2012 Wiley Periodicals, Inc.

Self-regulation, motivation, and math achievement in middle school: variations across grade level and math context.

PubMed

Cleary, Timothy J; Chen, Peggy P

2009-10-01

The current study examined grade level, achievement group, and math-course-type differences in student self-regulation and motivation in a sample of 880 suburban middle-school students. Analysis of variance was utilized to assess group differences in student self-regulation and motivation, and linear regression analysis was used to identify variables that best predicted students' use of regulatory strategies. A key finding was that although seventh graders exhibited a more maladaptive self-regulation and motivation profile than sixth graders, achievement groups in seventh grade (high, moderate, low) were more clearly differentiated across both self-regulation and motivation than achievement groups in sixth grade. The pattern of achievement group differences also varied across math course type, as self-regulation and motivation processes more consistently differentiated achievement groups in advanced classes than regular math courses. Finally, task interest was shown to be the primary motivational predictor of students' use of regulatory strategies during math learning. The study highlights the importance of identifying shifting student motivation and self-regulation during the early middle school years and the potential role that context may have on these processes.

Phytohormones and microRNAs as sensors and regulators of leaf senescence: assigning macro roles to small molecules.

PubMed

Sarwat, Maryam; Naqvi, Afsar Raza; Ahmad, Parvaiz; Ashraf, Muhammad; Akram, Nudrat Aisha

2013-12-01

Ageing or senescence is an intricate and highly synchronized developmental phase in the life of plant parts including leaf. Senescence not only means death of a plant part, but during this process, different macromolecules undergo degradation and the resulting components are transported to other parts of the plant. During the period from when a leaf is young and green to the stage when it senesces, a multitude of factors such as hormones, environmental factors and senescence associated genes (SAGs) are involved. Plant hormones including salicylic acid, abscisic acid, jasmonic acid and ethylene advance leaf senescence, whereas others like cytokinins, gibberellins, and auxins delay this process. The environmental factors which generally affect plant development and growth, can hasten senescence, the examples being nutrient dearth, water stress, pathogen attack, radiations, high temperature and light intensity, waterlogging, and air, water or soil contamination. Other important influences include carbohydrate accumulation and high carbon/nitrogen level. To date, although several genes involved in this complex process have been identified, still not much information exists in the literature on the signalling mechanism of leaf senescence. Now, the Arabidopsis mutants have paved our way and opened new vistas to elucidate the signalling mechanism of leaf senescence for which various mutants are being utilized. Recent studies demonstrating the role of microRNAs in leaf senescence have reinforced our knowledge of this intricate process. This review provides a comprehensive and critical analysis of the information gained particularly on the roles of several plant growth regulators and microRNAs in regulation of leaf senescence. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Roger Lew; Ronald L. Boring; Thomas A. Ulrich

Operators of critical processes, such as nuclear power production, must contend with highly complex systems, procedures, and regulations. Developing human-machine interfaces (HMIs) that better support operators is a high priority for ensuring the safe and reliable operation of critical processes. Human factors engineering (HFE) provides a rich and mature set of tools for evaluating the performance of HMIs, but the set of tools for developing and designing HMIs is still in its infancy. Here we propose that Microsoft Windows Presentation Foundation (WPF) is well suited for many roles in the research and development of HMIs for process control.

Preferential Ty1 retromobility in mother cells and nonquiescent stationary phase cells is associated with increased concentrations of total Gag or processed Gag and is inhibited by exposure to a high concentration of calcium.

PubMed

Peifer, Andrew C; Maxwell, Patrick H

2018-03-21

Retrotransposons are abundant mobile DNA elements in eukaryotic genomes that are more active with age in diverse species. Details of the regulation and consequences of retrotransposon activity during aging remain to be determined. Ty1 retromobility in Saccharomyces cerevisiae is more frequent in mother cells compared to daughter cells, and we found that Ty1 was more mobile in nonquiescent compared to quiescent subpopulations of stationary phase cells. This retromobility asymmetry was absent in mutant strains lacking BRP1 that have reduced expression of the essential Pma1p plasma membrane proton pump, lacking the mRNA decay gene LSM1 , and in cells exposed to a high concentration of calcium. Mother cells had higher levels of Ty1 Gag protein than daughters. The proportion of protease-processed Gag decreased as cells transitioned to stationary phase, processed Gag was the dominant form in nonquiescent cells, but was virtually absent from quiescent cells. Treatment with calcium reduced total Gag levels and the proportion of processed Gag, particularly in mother cells. We also found that Ty1 reduced the fitness of proliferating but not stationary phase cells. These findings may be relevant to understanding regulation and consequences of retrotransposons during aging in other organisms, due to conserved impacts and regulation of retrotransposons.

Preferential Ty1 retromobility in mother cells and nonquiescent stationary phase cells is associated with increased concentrations of total Gag or processed Gag and is inhibited by exposure to a high concentration of calcium

PubMed Central

Peifer, Andrew C.

2018-01-01

Retrotransposons are abundant mobile DNA elements in eukaryotic genomes that are more active with age in diverse species. Details of the regulation and consequences of retrotransposon activity during aging remain to be determined. Ty1 retromobility in Saccharomyces cerevisiae is more frequent in mother cells compared to daughter cells, and we found that Ty1 was more mobile in nonquiescent compared to quiescent subpopulations of stationary phase cells. This retromobility asymmetry was absent in mutant strains lacking BRP1 that have reduced expression of the essential Pma1p plasma membrane proton pump, lacking the mRNA decay gene LSM1, and in cells exposed to a high concentration of calcium. Mother cells had higher levels of Ty1 Gag protein than daughters. The proportion of protease-processed Gag decreased as cells transitioned to stationary phase, processed Gag was the dominant form in nonquiescent cells, but was virtually absent from quiescent cells. Treatment with calcium reduced total Gag levels and the proportion of processed Gag, particularly in mother cells. We also found that Ty1 reduced the fitness of proliferating but not stationary phase cells. These findings may be relevant to understanding regulation and consequences of retrotransposons during aging in other organisms, due to conserved impacts and regulation of retrotransposons. PMID:29562219

G-Quadruplexes in DNA Replication: A Problem or a Necessity?

PubMed

Valton, Anne-Laure; Prioleau, Marie-Noëlle

2016-11-01

DNA replication is a highly regulated process that ensures the correct duplication of the genome at each cell cycle. A precise cell type-specific temporal program controls the duplication of complex vertebrate genomes in an orderly manner. This program is based on the regulation of both replication origin firing and replication fork progression. G-quadruplexes (G4s), DNA secondary structures displaying noncanonical Watson-Crick base pairing, have recently emerged as key controllers of genome duplication. Here we discuss the various means by which G4s affect this fundamental cellular process. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sexually Dimorphic Gene Expression Associated with Growth and Reproduction of Tongue Sole (Cynoglossus semilaevis) Revealed by Brain Transcriptome Analysis.

PubMed

Wang, Pingping; Zheng, Min; Liu, Jian; Liu, Yongzhuang; Lu, Jianguo; Sun, Xiaowen

2016-08-26

In this study, we performed a comprehensive analysis of the transcriptome of one- and two-year-old male and female brains of Cynoglossus semilaevis by high-throughput Illumina sequencing. A total of 77,066 transcripts, corresponding to 21,475 unigenes, were obtained with a N50 value of 4349 bp. Of these unigenes, 33 genes were found to have significant differential expression and potentially associated with growth, from which 18 genes were down-regulated and 12 genes were up-regulated in two-year-old males, most of these genes had no significant differences in expression among one-year-old males and females and two-year-old females. A similar analysis was conducted to look for genes associated with reproduction; 25 genes were identified, among them, five genes were found to be down regulated and 20 genes up regulated in two-year-old males, again, most of the genes had no significant expression differences among the other three. The performance of up regulated genes in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was significantly different between two-year-old males and females. Males had a high gene expression in genetic information processing, while female's highly expressed genes were mainly enriched on organismal systems. Our work identified a set of sex-biased genes potentially associated with growth and reproduction that might be the candidate factors affecting sexual dimorphism of tongue sole, laying the foundation to understand the complex process of sex determination of this economic valuable species.

Identification of MicroRNAs and their Targets Associated with Embryo Abortion during Chrysanthemum Cross Breeding via High-Throughput Sequencing.

PubMed

Zhang, Fengjiao; Dong, Wen; Huang, Lulu; Song, Aiping; Wang, Haibin; Fang, Weimin; Chen, Fadi; Teng, Nianjun

2015-01-01

MicroRNAs (miRNAs) are important regulators in plant development. They post-transcriptionally regulate gene expression during various biological and metabolic processes by binding to the 3'-untranslated region of target mRNAs to facilitate mRNA degradation or inhibit translation. Chrysanthemum (Chrysanthemum morifolium) is one of the most important ornamental flowers with increasing demand each year. However, embryo abortion is the main reason for chrysanthemum cross breeding failure. To date, there have been no experiments examining the expression of miRNAs associated with chrysanthemum embryo development. Therefore, we sequenced three small RNA libraries to identify miRNAs and their functions. Our results will provide molecular insights into chrysanthemum embryo abortion. Three small RNA libraries were built from normal chrysanthemum ovules at 12 days after pollination (DAP), and normal and abnormal chrysanthemum ovules at 18 DAP. We validated 228 miRNAs with significant changes in expression frequency during embryonic development. Comparative profiling revealed that 69 miRNAs exhibited significant differential expression between normal and abnormal embryos at 18 DAP. In addition, a total of 1037 miRNA target genes were predicted, and their annotations were defined by transcriptome data. Target genes associated with metabolic pathways were most highly represented according to the annotation. Moreover, 52 predicted target genes were identified to be associated with embryonic development, including 31 transcription factors and 21 additional genes. Gene ontology (GO) annotation also revealed that high-ranking miRNA target genes related to cellular processes and metabolic processes were involved in transcription regulation and the embryo developmental process. The present study generated three miRNA libraries and gained information on miRNAs and their targets in the chrysanthemum embryo. These results enrich the growing database of new miRNAs and lay the foundation for the further understanding of miRNA biological function in the regulation of chrysanthemum embryo abortion.

Online Reflective Writing Mechanisms and Its Effects on Self-Regulated Learning: A Case of Web-Based Portfolio Assessment System

ERIC Educational Resources Information Center

Liang, Chaoyun; Chang, Chi-Cheng; Shu, Kuen-Ming; Tseng, Ju-Shih; Lin, Chun-Yu

2016-01-01

The purpose of the present study was to design reflective writing mechanisms in a web-based portfolio assessment system and evaluate its effects on self-regulated learning. Participants were two classes of juniors majoring in data processing and taking a course called "Website design" at a vocational high school in Taiwan. One class was…

The profile of students’ self-regulated learning at vocational high school

NASA Astrophysics Data System (ADS)

Ciptaningtyas, Asih; Pratiwi, Hasih; Mardiyana

2018-05-01

Self-regulated learning is a power in the individual through the individualization process. Self-regulated learning will occur when the student is active to control himself from everything done, plan something, evaluate, and deeply reflect what he has experienced. This study aims to determine the profile of students’ self-regulated learning in SMK Giripuro, Sumpiuh, Banyumas Regency. This study is a qualitative research with questionnaire and interview methods. This study used triangulation method technique to obtain from the questionnaire and interview to get valid data. The subjects in this study are three 10th Grade students who have different self-regulated learning in SMK Giripuro Sumpiuh. The results showed that the high self-regulated learning student has characteristics: 1) independent of others, 2) believe in their abilities, 3) awareness in learning, and 4) be able to reflect on their learning. Medium self-regulated learning student has characteristics: 1) independent of others, 2) believe in their abilities, 3) awareness in learning, and 4) do not reflect on learning. Low self-regulated learning student has characteristics: 1) dependent on others, 2) do not believe in their abilities, 3) lack awareness of learning, and 4) do not reflect on learning.

High-resolution time series of Pseudomonas aeruginosa gene expression and rhamnolipid secretion through growth curve synchronization.

PubMed

van Ditmarsch, Dave; Xavier, João B

2011-06-17

Online spectrophotometric measurements allow monitoring dynamic biological processes with high-time resolution. Contrastingly, numerous other methods require laborious treatment of samples and can only be carried out offline. Integrating both types of measurement would allow analyzing biological processes more comprehensively. A typical example of this problem is acquiring quantitative data on rhamnolipid secretion by the opportunistic pathogen Pseudomonas aeruginosa. P. aeruginosa cell growth can be measured by optical density (OD600) and gene expression can be measured using reporter fusions with a fluorescent protein, allowing high time resolution monitoring. However, measuring the secreted rhamnolipid biosurfactants requires laborious sample processing, which makes this an offline measurement. Here, we propose a method to integrate growth curve data with endpoint measurements of secreted metabolites that is inspired by a model of exponential cell growth. If serial diluting an inoculum gives reproducible time series shifted in time, then time series of endpoint measurements can be reconstructed using calculated time shifts between dilutions. We illustrate the method using measured rhamnolipid secretion by P. aeruginosa as endpoint measurements and we integrate these measurements with high-resolution growth curves measured by OD600 and expression of rhamnolipid synthesis genes monitored using a reporter fusion. Two-fold serial dilution allowed integrating rhamnolipid measurements at a ~0.4 h-1 frequency with high-time resolved data measured at a 6 h-1 frequency. We show how this simple method can be used in combination with mutants lacking specific genes in the rhamnolipid synthesis or quorum sensing regulation to acquire rich dynamic data on P. aeruginosa virulence regulation. Additionally, the linear relation between the ratio of inocula and the time-shift between curves produces high-precision measurements of maximum specific growth rates, which were determined with a precision of ~5.4%. Growth curve synchronization allows integration of rich time-resolved data with endpoint measurements to produce time-resolved quantitative measurements. Such data can be valuable to unveil the dynamic regulation of virulence in P. aeruginosa. More generally, growth curve synchronization can be applied to many biological systems thus helping to overcome a key obstacle in dynamic regulation: the scarceness of quantitative time-resolved data.

Identification of Parent-Child Interaction Characteristics of High and Low Achieving Elementary Students.

ERIC Educational Resources Information Center

Portes, Pedro R.; And Others

The present study was designed to identify parent-child interaction patterns that might differentiate bright from below average elementary students in order to test the hypothesis that environmental processes related to regulation of executive processes influence both children's learning and developmental level. Thirty-two mother-child dyads (16…

Control of transcriptional pausing by biased thermal fluctuations on repetitive genomic sequences

PubMed Central

Imashimizu, Masahiko; Afek, Ariel; Takahashi, Hiroki; Lubkowska, Lucyna; Lukatsky, David B.

2016-01-01

In the process of transcription elongation, RNA polymerase (RNAP) pauses at highly nonrandom positions across genomic DNA, broadly regulating transcription; however, molecular mechanisms responsible for the recognition of such pausing positions remain poorly understood. Here, using a combination of statistical mechanical modeling and high-throughput sequencing and biochemical data, we evaluate the effect of thermal fluctuations on the regulation of RNAP pausing. We demonstrate that diffusive backtracking of RNAP, which is biased by repetitive DNA sequence elements, causes transcriptional pausing. This effect stems from the increased microscopic heterogeneity of an elongation complex, and thus is entropy-dominated. This report shows a linkage between repetitive sequence elements encoded in the genome and regulation of RNAP pausing driven by thermal fluctuations. PMID:27830653

SDF1 Reduces Interneuron Leading Process Branching through Dual Regulation of Actin and Microtubules

PubMed Central

Lysko, Daniel E.; Putt, Mary

2014-01-01

Normal cerebral cortical function requires a highly ordered balance between projection neurons and interneurons. During development these two neuronal populations migrate from distinct progenitor zones to form the cerebral cortex, with interneurons originating in the more distant ganglionic eminences. Moreover, deficits in interneurons have been linked to a variety of neurodevelopmental disorders underscoring the importance of understanding interneuron development and function. We, and others, have identified SDF1 signaling as one important modulator of interneuron migration speed and leading process branching behavior in mice, although how SDF1 signaling impacts these behaviors remains unknown. We previously found SDF1 inhibited leading process branching while increasing the rate of migration. We have now mechanistically linked SDF1 modulation of leading process branching behavior to a dual regulation of both actin and microtubule organization. We find SDF1 consolidates actin at the leading process tip by de-repressing calpain protease and increasing proteolysis of branched-actin-supporting cortactin. Additionally, SDF1 stabilizes the microtubule array in the leading process through activation of the microtubule-associated protein doublecortin (DCX). DCX stabilizes the microtubule array by bundling microtubules within the leading process, reducing branching. These data provide mechanistic insight into the regulation of interneuron leading process dynamics during neuronal migration in mice and provides insight into how cortactin and DCX, a known human neuronal migration disorder gene, participate in this process. PMID:24695713

Electron-processing technology: A promising application for the viscose industry

NASA Astrophysics Data System (ADS)

Stepanik, T. M.; Rajagopal, S.; Ewing, D.; Whitehouse, R.

1998-06-01

In marketing its IMPELA ® line of high power, high-throughput industrial accelerators, Atomic Energy of Canada Limited (AECL) is working with viscose (rayon) companies world-wide to integrate electron-processing technology as part of the viscose manufacturing process. The viscose industry converts cellulose wood pulp into products such as staple fiber, filament, cord, film, packaging, and non-edible sausage casings. This multibillion dollar industry is currently suffering from high production costs, and is facing increasingly stringent environmental regulations. The use of electron-treated pulp can significantly lower production costs and can provide equally significant environmental benefits. This paper describes our current understanding of the benefits of using electron-treated pulp in this process, and AECL's efforts in developing this technology.

A Protocol-Analytic Study of Metacognition in Mathematical Problem Solving.

ERIC Educational Resources Information Center

Cai, Jinfa

1994-01-01

Metacognitive behaviors of subjects having high (n=2) and low (n=2) levels of mathematical experience were compared across four cognitive processes in mathematical problem solving: orientation, organization, execution, and verification. High-experience subjects engaged in self-regulation and spent more time on orientation and organization. (36…

Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells

PubMed Central

Heery, Richard; Finn, Stephen P.; Cuffe, Sinead; Gray, Steven G.

2017-01-01

Epithelial mesenchymal transition (EMT), the adoption by epithelial cells of a mesenchymal-like phenotype, is a process co-opted by carcinoma cells in order to initiate invasion and metastasis. In addition, it is becoming clear that is instrumental to both the development of drug resistance by tumour cells and in the generation and maintenance of cancer stem cells. EMT is thus a pivotal process during tumour progression and poses a major barrier to the successful treatment of cancer. Non-coding RNAs (ncRNA) often utilize epigenetic programs to regulate both gene expression and chromatin structure. One type of ncRNA, called long non-coding RNAs (lncRNAs), has become increasingly recognized as being both highly dysregulated in cancer and to play a variety of different roles in tumourigenesis. Indeed, over the last few years, lncRNAs have rapidly emerged as key regulators of EMT in cancer. In this review, we discuss the lncRNAs that have been associated with the EMT process in cancer and the variety of molecular mechanisms and signalling pathways through which they regulate EMT, and finally discuss how these EMT-regulating lncRNAs impact on both anti-cancer drug resistance and the cancer stem cell phenotype. PMID:28430163

The bromodomain protein BRD4 regulates splicing during heat shock

PubMed Central

Hussong, Michelle; Kaehler, Christian; Kerick, Martin; Grimm, Christina; Franz, Alexandra; Timmermann, Bernd; Welzel, Franziska; Isensee, Jörg; Hucho, Tim; Krobitsch, Sylvia; Schweiger, Michal R.

2017-01-01

The cellular response to heat stress is an ancient and evolutionarily highly conserved defence mechanism characterised by the transcriptional up-regulation of cyto-protective genes and a partial inhibition of splicing. These features closely resemble the proteotoxic stress response during tumor development. The bromodomain protein BRD4 has been identified as an integral member of the oxidative stress as well as of the inflammatory response, mainly due to its role in the transcriptional regulation process. In addition, there are also several lines of evidence implicating BRD4 in the splicing process. Using RNA-sequencing we found a significant increase in splicing inhibition, in particular intron retentions (IR), following heat treatment in BRD4-depleted cells. This leads to a decrease of mRNA abundancy of the affected transcripts, most likely due to premature termination codons. Subsequent experiments revealed that BRD4 interacts with the heat shock factor 1 (HSF1) such that under heat stress BRD4 is recruited to nuclear stress bodies and non-coding SatIII RNA transcripts are up-regulated. These findings implicate BRD4 as an important regulator of splicing during heat stress. Our data which links BRD4 to the stress induced splicing process may provide novel mechanisms of BRD4 inhibitors in regard to anti-cancer therapies. PMID:27536004

Enhancing Decision-Making in STSE Education by Inducing Reflection and Self-Regulated Learning

NASA Astrophysics Data System (ADS)

Gresch, Helge; Hasselhorn, Marcus; Bögeholz, Susanne

2017-02-01

Thoughtful decision-making to resolve socioscientific issues is central to science, technology, society, and environment (STSE) education. One approach for attaining this goal involves fostering students' decision-making processes. Thus, the present study explores whether the application of decision-making strategies, combined with reflections on the decision-making processes of others, enhances decision-making competence. In addition, this study examines whether this process is supported by elements of self-regulated learning, i.e., self-reflection regarding one's own performance and the setting of goals for subsequent tasks. A computer-based training program which involves the resolution of socioscientific issues related to sustainable development was developed in two versions: with and without elements of self-regulated learning. Its effects on decision-making competence were analyzed using a pre test-post test follow-up control-group design ( N = 242 high school students). Decision-making competence was assessed using an open-ended questionnaire that focused on three facets: consideration of advantages and disadvantages, metadecision aspects, and reflection on the decision-making processes of others. The findings suggest that students in both training groups incorporated aspects of metadecision into their statements more often than students in the control group. Furthermore, both training groups were more successful in reflecting on the decision-making processes of others. The students who received additional training in self-regulated learning showed greater benefits in terms of metadecision aspects and reflection, and these effects remained significant two months later. Overall, our findings demonstrate that the application of decision-making strategies, combined with reflections on the decision-making process and elements of self-regulated learning, is a fruitful approach in STSE education.

[Regulatory policies and public opinion: the case of smoking].

PubMed

Saltó, Esteve; Joan R, Villalbí; Valverde, Araceli; Baranda, Lucía; Plasencia, Antoni

2006-01-01

Collecting and disseminating information about the public opinion on a regulatory process gives visibility to the silent social support and facilitates the process, which often confronts resistance from interest groups. This paper presents a survey about a proposed legislation on tobacco in its final stages and its results, and some considerations on the use of this sort of information in change processes. Cross sectional descriptive study. In December 2005 a brief telephone survey was made to a population sample of 18 and more years of age (N=830) in Catalonia (Spain). The questionnaire explored opinions on the proposed regulations under discussion. We present the degree of support and the rating of nine regulatory measures, stratified by the respondents use of tobacco. Daily smokers are 26.3% of the surveyed population. Awareness and general support for tobacco regulation are very high. Aspects with wider support include bans on sales to minors (97.3%), smoking in enclosed public places (92.8%) and workplaces (89%), and publicity (90.8%). The aspect with less social support is banning smoking in bars and cafes (80.2%). The population supports widely tobacco regulation. This reinforces the process and weakens the arguments of those against it. Although smokers are less supportive, most of them accept the regulations, except for limitations in bars and cafes.

SpoVT: From Fine-Tuning Regulator in Bacillus subtilis to Essential Sporulation Protein in Bacillus cereus

PubMed Central

Eijlander, Robyn T.; Holsappel, Siger; de Jong, Anne; Ghosh, Abhinaba; Christie, Graham; Kuipers, Oscar P.

2016-01-01

Sporulation is a highly sophisticated developmental process adopted by most Bacilli as a survival strategy to withstand extreme conditions that normally do not support microbial growth. A complicated regulatory cascade, divided into various stages and taking place in two different compartments of the cell, involves a number of primary and secondary regulator proteins that drive gene expression directed toward the formation and maturation of an endospore. Such regulator proteins are highly conserved among various spore formers. Despite this conservation, both regulatory and phenotypic differences are observed between different species of spore forming bacteria. In this study, we demonstrate that deletion of the regulatory sporulation protein SpoVT results in a severe sporulation defect in Bacillus cereus, whereas this is not observed in Bacillus subtilis. Although spores are initially formed, the process is stalled at a later stage in development, followed by lysis of the forespore and the mother cell. A transcriptomic investigation of B. cereus ΔspoVT shows upregulation of genes involved in germination, potentially leading to premature lysis of prespores formed. Additionally, extreme variation in the expression of species-specific genes of unknown function was observed. Introduction of the B. subtilis SpoVT protein could partly restore the sporulation defect in the B. cereus spoVT mutant strain. The difference in phenotype is thus more than likely explained by differences in promoter targets rather than differences in mode of action of the conserved SpoVT regulator protein. This study stresses that evolutionary variances in regulon members of sporulation regulators can have profound effects on the spore developmental process and that mere protein homology is not a foolproof predictor of similar phenotypes. PMID:27790204

SpoVT: From Fine-Tuning Regulator in Bacillus subtilis to Essential Sporulation Protein in Bacillus cereus.

PubMed

Eijlander, Robyn T; Holsappel, Siger; de Jong, Anne; Ghosh, Abhinaba; Christie, Graham; Kuipers, Oscar P

2016-01-01

Sporulation is a highly sophisticated developmental process adopted by most Bacilli as a survival strategy to withstand extreme conditions that normally do not support microbial growth. A complicated regulatory cascade, divided into various stages and taking place in two different compartments of the cell, involves a number of primary and secondary regulator proteins that drive gene expression directed toward the formation and maturation of an endospore. Such regulator proteins are highly conserved among various spore formers. Despite this conservation, both regulatory and phenotypic differences are observed between different species of spore forming bacteria. In this study, we demonstrate that deletion of the regulatory sporulation protein SpoVT results in a severe sporulation defect in Bacillus cereus , whereas this is not observed in Bacillus subtilis . Although spores are initially formed, the process is stalled at a later stage in development, followed by lysis of the forespore and the mother cell. A transcriptomic investigation of B. cereus Δ spoVT shows upregulation of genes involved in germination, potentially leading to premature lysis of prespores formed. Additionally, extreme variation in the expression of species-specific genes of unknown function was observed. Introduction of the B. subtilis SpoVT protein could partly restore the sporulation defect in the B. cereus spoVT mutant strain. The difference in phenotype is thus more than likely explained by differences in promoter targets rather than differences in mode of action of the conserved SpoVT regulator protein. This study stresses that evolutionary variances in regulon members of sporulation regulators can have profound effects on the spore developmental process and that mere protein homology is not a foolproof predictor of similar phenotypes.

Microarray-based analysis of the lung recovery process after stainless-steel welding fume exposure in Sprague-Dawley rats.

PubMed

Oh, Jung-Hwa; Yang, Mi-jin; Yang, Young-Su; Park, Han-Jin; Heo, Sun Hee; Lee, Eun-Hee; Song, Chang-Woo; Yoon, Seokjoo

2009-02-01

Repeated exposure to welding fumes promotes a reversible increase in pulmonary disease risk, but the molecular mechanisms by which welding fumes induce lung injury and how the lung recovers from such insults are unclear. In the present study, pulmonary function and gene-expression profiles in the lung were analyzed by Affymetrix GeneChip microarray after 30 days of consecutive exposure to manual metal arc welding combined with stainless-steel (MMA-SS) welding fumes, and again after 30 days of recovery from MMA-SS fume exposure. In total, 577 genes were identified as being either up-regulated or down-regulated (over twofold changes, p < 0.05) in the lungs of low-dose or high-dose groups. Differentially expressed genes were classified based on a k-means clustering algorithm and biological functions and molecular networks were further analyzed using Ingenuity Pathways Analysis. Among the genes affected by exposure to or recovery from MMA-SS fumes, the transcriptional changes of 13 genes that were highly altered by treatment were confirmed by quantitative real-time PCR. Notably, Mmp12, Cd5l, Ccl7, Cxcl5, and Spp1 related to the immune response were up-regulated only in the exposure group, whereas Trem2, IgG-2a, Igh-1a, and Igh were persistently up-regulated in both the exposure and recovery groups. In addition, several genes that might play a role in the repair process of the lung were up-regulated exclusively in the recovery group. Collectively, these data may help elucidate the molecular mechanism of the recovery process of the lung after welding fume exposure.

Transcriptional regulation of hepatic lipogenesis.

PubMed

Wang, Yuhui; Viscarra, Jose; Kim, Sun-Joong; Sul, Hei Sook

2015-11-01

Fatty acid and fat synthesis in the liver is a highly regulated metabolic pathway that is important for very low-density lipoprotein (VLDL) production and thus energy distribution to other tissues. Having common features at their promoter regions, lipogenic genes are coordinately regulated at the transcriptional level. Transcription factors, such as upstream stimulatory factors (USFs), sterol regulatory element-binding protein 1C (SREBP1C), liver X receptors (LXRs) and carbohydrate-responsive element-binding protein (ChREBP) have crucial roles in this process. Recently, insights have been gained into the signalling pathways that regulate these transcription factors. After feeding, high blood glucose and insulin levels activate lipogenic genes through several pathways, including the DNA-dependent protein kinase (DNA-PK), atypical protein kinase C (aPKC) and AKT-mTOR pathways. These pathways control the post-translational modifications of transcription factors and co-regulators, such as phosphorylation, acetylation or ubiquitylation, that affect their function, stability and/or localization. Dysregulation of lipogenesis can contribute to hepatosteatosis, which is associated with obesity and insulin resistance.

Silk-regulated hierarchical hollow magnetite/carbon nanocomposite spheroids for lithium-ion battery anodes.

PubMed

Sheng, Weiqin; Zhu, Guobin; Kaplan, David L; Cao, Chuanbao; Zhu, Hesun; Lu, Qiang

2015-03-20

Hierarchical olive-like structured carbon-Fe3O4 nanocomposite particles composed of a hollow interior and a carbon coated surface are prepared by a facile, silk protein-assisted hydrothermal method. Silk nanofibers as templates and carbon precursors first regulate the formation of hollow Fe2O3 microspheres and then they are converted into carbon by a reduction process into Fe3O4. This process significantly simplifies the fabrication and carbon coating processes to form complex hollow structures. When tested as anode materials for lithium-ion batteries, these hollow carbon-coated particles exhibit high capacity (900 mAh g(-1)), excellent cycle stability (180 cycles) and rate performance due to their unique hierarchical hollow structure and carbon coating.

LYRATE Is a Key Regulator of Leaflet Initiation and Lamina Outgrowth in Tomato[C][W][OA

PubMed Central

David-Schwartz, Rakefet; Koenig, Daniel; Sinha, Neelima R.

2009-01-01

Development of the flattened laminar structure in plant leaves requires highly regulated cell division and expansion patterns. Although tight regulation of these processes is essential during leaf development, leaf shape is highly diverse across the plant kingdom, implying that patterning of growth must be amenable to evolutionary change. Here, we describe the molecular identification of the classical tomato (Solanum lycopersicum) mutant lyrate, which is impaired in outgrowth of leaflet primodia and laminar tissues during compound leaf development. We found that the lyrate phenotype results from a loss-of-function mutation of the tomato JAGGED homolog, a well-described positive regulator of cell division in lateral organs. We demonstrate that LYRATE coordinates lateral outgrowth in the compound leaves of tomato by interacting with both the KNOX and auxin transcriptional networks and suggest that evolutionary changes in LYRATE expression may contribute to the fundamental difference between compound and simple leaves. PMID:19820188

Understanding splicing regulation through RNA splicing maps

PubMed Central

Witten, Joshua T.; Ule, Jernej

2011-01-01

Alternative splicing is a highly regulated process that greatly increases the proteome diversity and plays an important role in cellular differentiation and disease. Interactions between RNA-binding proteins (RBPs) and pre-mRNA are the principle regulator of splicing decisions. Findings from recent genome-wide studies of protein–RNA interactions have been combined with assays of the global effects of RBPs on splicing to create RNA splicing maps. These maps integrate information from all pre-mRNAs regulated by single RBPs to identify the global positioning principles guiding splicing regulation. Recent studies using this approach have identified a set of positional principles that are shared between diverse RBPs. Here, we discuss how insights from RNA splicing maps of different RBPs inform the mechanistic models of splicing regulation. PMID:21232811

A chronometric functional sub-network in the thalamo-cortical system regulates the flow of neural information necessary for conscious cognitive processes.

PubMed

León-Domínguez, Umberto; Vela-Bueno, Antonio; Froufé-Torres, Manuel; León-Carrión, Jose

2013-06-01

The thalamo-cortical system has been defined as a neural network associated with consciousness. While there seems to be wide agreement that the thalamo-cortical system directly intervenes in vigilance and arousal, a divergence of opinion persists regarding its intervention in the control of other cognitive processes necessary for consciousness. In the present manuscript, we provide a review of recent scientific findings on the thalamo-cortical system and its role in the control and regulation of the flow of neural information necessary for conscious cognitive processes. We suggest that the axis formed by the medial prefrontal cortex and different thalamic nuclei (reticular nucleus, intralaminar nucleus, and midline nucleus), represents a core component for consciousness. This axis regulates different cerebral structures which allow basic cognitive processes like attention, arousal and memory to emerge. In order to produce a synchronized coherent response, neural communication between cerebral structures must have exact timing (chronometry). Thus, a chronometric functional sub-network within the thalamo-cortical system keeps us in an optimal and continuous functional state, allowing high-order cognitive processes, essential to awareness and qualia, to take place. Copyright © 2013 Elsevier Ltd. All rights reserved.

DISCOVERY OF NOVEL GLUCOSE-REGULATED PROTEINS IN ISOLATED HUMAN PANCREATIC ISLETS USING LC-MS/MS-BASED PROTEOMICS

PubMed Central

Schrimpe-Rutledge, Alexandra C.; Fontès, Ghislaine; Gritsenko, Marina A.; Norbeck, Angela D.; Anderson, David J.; Waters, Katrina M.; Adkins, Joshua N.; Smith, Richard D.; Poitout, Vincent; Metz, Thomas O.

2012-01-01

The prevalence of diabetes mellitus is increasing dramatically throughout the world, and the disease has become a major public health issue. The most common form of the disease, type 2 diabetes, is characterized by insulin resistance and insufficient insulin production from the pancreatic beta-cell. Since glucose is the most potent regulator of beta-cell function under physiological conditions, identification of the insulin secretory defect underlying type 2 diabetes requires a better understanding of glucose regulation of human beta-cell function. To this aim, a bottom-up LC-MS/MS-based proteomics approach was used to profile pooled islets from multiple donors under basal (5 mM) or high (15 mM) glucose conditions. Our analysis discovered 256 differentially abundant proteins (~p<0.05) after 24 h of high glucose exposure from more than 4500 identified in total. Several novel glucose-regulated proteins were elevated under high glucose conditions, including regulators of mRNA splicing (Pleiotropic regulator 1), processing (Retinoblastoma binding protein 6), and function (Nuclear RNA export factor 1), in addition to Neuron navigator 1 and Plasminogen activator inhibitor 1. Proteins whose abundances markedly decreased during incubation at 15 mM glucose included Bax inhibitor 1 and Synaptotagmin-17. Up-regulation of Dicer 1 and SLC27A2 and down-regulation of Phospholipase Cβ4 were confirmed by Western blots. Many proteins found to be differentially abundant after high glucose stimulation are annotated as uncharacterized or hypothetical. These findings expand our knowledge of glucose regulation of the human islet proteome and suggest many hitherto unknown responses to glucose that require additional studies to explore novel functional roles. PMID:22578083

Sponge budding is a spatiotemporal morphological patterning process: Insights from synchrotron radiation-based x-ray microtomography into the asexual reproduction of Tethya wilhelma.

PubMed

Hammel, Jörg U; Herzen, Julia; Beckmann, Felix; Nickel, Michael

2009-09-08

Primary agametic-asexual reproduction mechanisms such as budding and fission are present in all non-bilaterian and many bilaterian animal taxa and are likely to be metazoan ground pattern characters. Cnidarians display highly organized and regulated budding processes. In contrast, budding in poriferans was thought to be less specific and related to the general ability of this group to reorganize their tissues. Here we test the hypothesis of morphological pattern formation during sponge budding. We investigated the budding process in Tethya wilhelma (Demospongiae) by applying 3D morphometrics to high resolution synchrotron radiation-based x-ray microtomography (SR-muCT) image data. We followed the morphogenesis of characteristic body structures and identified distinct morphological states which indeed reveal characteristic spatiotemporal morphological patterns in sponge bud development. We discovered the distribution of skeletal elements, canal system and sponge tissue to be based on a sequential series of distinct morphological states. Based on morphometric data we defined four typical bud stages. Once they have reached the final stage buds are released as fully functional juvenile sponges which are morphologically and functionally equivalent to adult specimens. Our results demonstrate that budding in demosponges is considerably more highly organized and regulated than previously assumed. Morphological pattern formation in asexual reproduction with underlying genetic regulation seems to have evolved early in metazoans and was likely part of the developmental program of the last common ancestor of all Metazoa (LCAM).

Sponge budding is a spatiotemporal morphological patterning process: Insights from synchrotron radiation-based x-ray microtomography into the asexual reproduction of Tethya wilhelma

PubMed Central

Hammel, Jörg U; Herzen, Julia; Beckmann, Felix; Nickel, Michael

2009-01-01

Background Primary agametic-asexual reproduction mechanisms such as budding and fission are present in all non-bilaterian and many bilaterian animal taxa and are likely to be metazoan ground pattern characters. Cnidarians display highly organized and regulated budding processes. In contrast, budding in poriferans was thought to be less specific and related to the general ability of this group to reorganize their tissues. Here we test the hypothesis of morphological pattern formation during sponge budding. Results We investigated the budding process in Tethya wilhelma (Demospongiae) by applying 3D morphometrics to high resolution synchrotron radiation-based x-ray microtomography (SR-μCT) image data. We followed the morphogenesis of characteristic body structures and identified distinct morphological states which indeed reveal characteristic spatiotemporal morphological patterns in sponge bud development. We discovered the distribution of skeletal elements, canal system and sponge tissue to be based on a sequential series of distinct morphological states. Based on morphometric data we defined four typical bud stages. Once they have reached the final stage buds are released as fully functional juvenile sponges which are morphologically and functionally equivalent to adult specimens. Conclusion Our results demonstrate that budding in demosponges is considerably more highly organized and regulated than previously assumed. Morphological pattern formation in asexual reproduction with underlying genetic regulation seems to have evolved early in metazoans and was likely part of the developmental program of the last common ancestor of all Metazoa (LCAM). PMID:19737392

Self-reported tolerance influences prefrontal cortex hemodynamics and affective responses.

PubMed

Tempest, Gavin; Parfitt, Gaynor

2016-02-01

The relationship between cognitive and sensory processes in the brain contributes to the regulation of affective responses (pleasure-displeasure). Exercise can be used to manipulate sensory processes (by increasing physiological demand) in order to examine the role of dispositional traits that may influence an individual's ability to cognitively regulate these responses. With the use of near infrared spectroscopy, in this study we examined the influence of self-reported tolerance upon prefrontal cortex (PFC) hemodynamics and affective responses. The hemodynamic response was measured in individuals with high or low tolerance during an incremental exercise test. Sensory manipulation was standardized against metabolic processes (ventilatory threshold [VT] and respiratory compensation point [RCP]), and affective responses were recorded. The results showed that the high-tolerance group displayed a larger hemodynamic response within the right PFC above VT (which increased above RCP). The low-tolerance group showed a larger hemodynamic response within the left PFC above VT. The high-tolerance group reported a more positive/less negative affective response above VT. These findings provide direct neurophysiological evidence of differential hemodynamic responses within the PFC that are associated with tolerance in the presence of increased physiological demands. This study supports the role of dispositional traits and previous theorizing into the underlying mechanisms (cognitive vs. sensory processes) of affective responses.

The ESCRT regulator Did2 maintains the balance between long-distance endosomal transport and endocytic trafficking

PubMed Central

Haag, Carl

2017-01-01

In highly polarised cells, like fungal hyphae, early endosomes function in both endocytosis as well as long-distance transport of various cargo including mRNA and protein complexes. However, knowledge on the crosstalk between these seemingly different trafficking processes is scarce. Here, we demonstrate that the ESCRT regulator Did2 coordinates endosomal transport in fungal hyphae of Ustilago maydis. Loss of Did2 results in defective vacuolar targeting, less processive long-distance transport and abnormal shuttling of early endosomes. Importantly, the late endosomal protein Rab7 and vacuolar protease Prc1 exhibit increased shuttling on these aberrant endosomes suggesting defects in endosomal maturation and identity. Consistently, molecular motors fail to attach efficiently explaining the disturbed processive movement. Furthermore, the endosomal mRNP linker protein Upa1 is hardly present on endosomes resulting in defects in long-distance mRNA transport. In conclusion, the ESCRT regulator Did2 coordinates precise maturation of endosomes and thus provides the correct membrane identity for efficient endosomal long-distance transport. PMID:28422978

Transcriptome Analysis of Al-Induced Genes in Buckwheat (Fagopyrum esculentum Moench) Root Apex: New Insight into Al Toxicity and Resistance Mechanisms in an Al Accumulating Species

PubMed Central

Xu, Jia Meng; Fan, Wei; Jin, Jian Feng; Lou, He Qiang; Chen, Wei Wei; Yang, Jian Li; Zheng, Shao Jian

2017-01-01

Relying on Al-activated root oxalate secretion, and internal detoxification and accumulation of Al, buckwheat is highly Al resistant. However, the molecular mechanisms responsible for these processes are still poorly understood. It is well-known that root apex is the critical region of Al toxicity that rapidly impairs a series of events, thus, resulting in inhibition of root elongation. Here, we carried out transcriptome analysis of the buckwheat root apex (0–1 cm) with regards to early response (first 6 h) to Al stress (20 μM), which is crucial for identification of both genes and processes involved in Al toxicity and tolerance mechanisms. We obtained 34,469 unigenes with 26,664 unigenes annotated in the NCBI database, and identified 589 up-regulated and 255 down-regulated differentially expressed genes (DEGs) under Al stress. Functional category analysis revealed that biological processes differ between up- and down-regulated genes, although ‘metabolic processes’ were the most affected category in both up- and down-regulated DEGs. Based on the data, it is proposed that Al stress affects a variety of biological processes that collectively contributes to the inhibition of root elongation. We identified 30 transporter genes and 27 transcription factor (TF) genes induced by Al. Gene homology analysis highlighted candidate genes encoding transporters associated with Al uptake, transport, detoxification, and accumulation. We also found that TFs play critical role in transcriptional regulation of Al resistance genes in buckwheat. In addition, gene duplication events are very common in the buckwheat genome, suggesting a possible role for gene duplication in the species’ high Al resistance. Taken together, the transcriptomic analysis of buckwheat root apex shed light on the processes that contribute to the inhibition of root elongation. Furthermore, the comprehensive analysis of both transporter genes and TF genes not only deep our understanding on the responses of buckwheat roots to Al toxicity but provide a good start for functional characterization of genes critical for Al tolerance. PMID:28702047

IGF-1 Receptor Differentially Regulates Spontaneous and Evoked Transmission via Mitochondria at Hippocampal Synapses

PubMed Central

Gazit, Neta; Vertkin, Irena; Shapira, Ilana; Helm, Martin; Slomowitz, Edden; Sheiba, Maayan; Mor, Yael; Rizzoli, Silvio; Slutsky, Inna

2016-01-01

Summary The insulin-like growth factor-1 receptor (IGF-1R) signaling is a key regulator of lifespan, growth, and development. While reduced IGF-1R signaling delays aging and Alzheimer’s disease progression, whether and how it regulates information processing at central synapses remains elusive. Here, we show that presynaptic IGF-1Rs are basally active, regulating synaptic vesicle release and short-term plasticity in excitatory hippocampal neurons. Acute IGF-1R blockade or transient knockdown suppresses spike-evoked synaptic transmission and presynaptic cytosolic Ca2+ transients, while promoting spontaneous transmission and resting Ca2+ level. This dual effect on transmitter release is mediated by mitochondria that attenuate Ca2+ buffering in the absence of spikes and decrease ATP production during spiking activity. We conclude that the mitochondria, activated by IGF-1R signaling, constitute a critical regulator of information processing in hippocampal neurons by maintaining evoked-to-spontaneous transmission ratio, while constraining synaptic facilitation at high frequencies. Excessive IGF-1R tone may contribute to hippocampal hyperactivity associated with Alzheimer’s disease. Video Abstract PMID:26804996

miRNA let-7b modulates macrophage polarization and enhances tumor-associated macrophages to promote angiogenesis and mobility in prostate cancer.

PubMed

Wang, Zhigang; Xu, Lu; Hu, Yinying; Huang, Yanqin; Zhang, Yujuan; Zheng, Xiufen; Wang, Shanshan; Wang, Yifan; Yu, Yanrong; Zhang, Meng; Yuan, Keng; Min, Weiping

2016-05-09

Macrophage polarization is a highly plastic physiological process that responds to a variety of environmental factors by changing macrophage phenotype and function. Tumor-associated macrophages (TAMs) are generally recognized as promoting tumor progression. As universal regulators, microRNAs (miRNAs) are functionally involved in numerous critical cellular processes including macrophage polarization. Let-7b, a miRNA, has differential expression patterns in inflamed tissues compared with healthy controls. However, whether and how miRNA let-7b regulates macrophage phenotype and function is unclear. In this report, we find that up-regulation of let-7b is characteristic of prostatic TAMs, and down-regulation of let-7b in TAMs leads to changes in expression profiles of inflammatory cytokines, such as IL-12, IL-23, IL-10 and TNF-α. As a result, TAMs treated with let-7b inhibitors reduce angiogenesis and prostate carcinoma (PCa) cell mobility. Let-7b may play a vital role in regulating macrophage polarization, thus modulating the prognosis of prostate cancer.

Members of the Dof transcription factor family in Triticum aestivum are associated with light-mediated gene regulation.

PubMed

Shaw, Lindsay M; McIntyre, C Lynne; Gresshoff, Peter M; Xue, Gang-Ping

2009-11-01

DNA binding with One Finger (Dof) protein is a plant-specific transcription factor implicated in the regulation of many important plant-specific processes, including photosynthesis and carbohydrate metabolism. This study has identified 31 Dof genes (TaDof) in bread wheat through extensive analysis of current nucleotide databases. Phylogenetic analysis suggests that the TaDof family can be divided into four clades. Expression analysis of the TaDof family across all major organs using quantitative RT-PCR and searches of the wheat genome array database revealed that the majority of TaDof members were predominately expressed in vegetative organs. A large number of TaDof members were down-regulated by drought and/or were responsive to the light and dark cycle. Further expression analysis revealed that light up-regulated TaDof members were highly correlated in expression with a number of genes that are involved in photosynthesis or sucrose transport. These data suggest that the TaDof family may have an important role in light-mediated gene regulation, including involvement in the photosynthetic process.

Transcriptomic variation of eyestalk reveals the genes and biological processes associated with molting in Portunus trituberculatus

PubMed Central

Zhang, Longtao; Liu, Ping; Li, Jian

2017-01-01

Background Molting is an essential biological process throughout the life history of crustaceans, which is regulated by many neuropeptide hormones expressed in the eyestalk. To better understand the molting mechanism in Portunus trituberculatus, we used digital gene expression (DGE) to analyze single eyestalk samples during the molting cycle by high-throughput sequencing. Results We obtained 14,387,942, 12,631,508 and 13,060,062 clean sequence reads from inter-molt (InM), pre-molt (PrM) and post-molt (PoM) cDNA libraries, respectively. A total of 1,394 molt-related differentially expressed genes (DEGs) were identified. GO and KEGG enrichment analysis identified some important processes and pathways with key roles in molting regulation, such as chitin metabolism, peptidase inhibitor activity, and the ribosome. We first observed a pattern associated with the neuromodulator-related pathways during the molting cycle, which were up-regulated in PrM and down-regulated in PoM. Four categories of important molting-related transcripts were clustered and most of them had similar expression patterns, which suggests that there is a connection between these genes throughout the molt cycle. Conclusion Our work is the first molt-related investigation of P. trituberculatus focusing on the eyestalk at the whole transcriptome level. Together, our results, including DEGs, identification of molting-related biological processes and pathways, and observed expression patterns of important genes, provide a novel insight into the function of the eyestalk in molting regulation. PMID:28394948

Transcriptome-Wide Identification of RNA Targets of Arabidopsis SERINE/ARGININE-RICH45 Uncovers the Unexpected Roles of This RNA Binding Protein in RNA Processing[OPEN

PubMed Central

Wang, Yajun; Hamilton, Michael; Ben-Hur, Asa; Reddy, Anireddy S.N.

2015-01-01

Plant SR45 and its metazoan ortholog RNPS1 are serine/arginine-rich (SR)-like RNA binding proteins that function in splicing/postsplicing events and regulate diverse processes in eukaryotes. Interactions of SR45 with both RNAs and proteins are crucial for regulating RNA processing. However, in vivo RNA targets of SR45 are currently unclear. Using RNA immunoprecipitation followed by high-throughput sequencing, we identified over 4000 Arabidopsis thaliana RNAs that directly or indirectly associate with SR45, designated as SR45-associated RNAs (SARs). Comprehensive analyses of these SARs revealed several roles for SR45. First, SR45 associates with and regulates the expression of 30% of abscisic acid (ABA) signaling genes at the postsplicing level. Second, although most SARs are derived from intron-containing genes, surprisingly, 340 SARs are derived from intronless genes. Expression analysis of the SARs suggests that SR45 differentially regulates intronless and intron-containing SARs. Finally, we identified four overrepresented RNA motifs in SARs that likely mediate SR45’s recognition of its targets. Therefore, SR45 plays an unexpected role in mRNA processing of intronless genes, and numerous ABA signaling genes are targeted for regulation at the posttranscriptional level. The diverse molecular functions of SR45 uncovered in this study are likely applicable to other species in view of its conservation across eukaryotes. PMID:26603559

Regulation of catalase expression in healthy and cancerous cells.

PubMed

Glorieux, Christophe; Zamocky, Marcel; Sandoval, Juan Marcelo; Verrax, Julien; Calderon, Pedro Buc

2015-10-01

Catalase is an important antioxidant enzyme that dismutates hydrogen peroxide into water and molecular oxygen. The catalase gene has all the characteristics of a housekeeping gene (no TATA box, no initiator element sequence, high GC content in promoter) and a core promoter that is highly conserved among species. We demonstrate in this review that within this core promoter, the presence of DNA binding sites for transcription factors, such as NF-Y and Sp1, plays an essential role in the positive regulation of catalase expression. Additional transcription factors, such as FoxO3a, are also involved in this regulatory process. There is strong evidence that the protein Akt/PKB in the PI3K signaling pathway plays a major role in the expression of catalase by modulating the activity of FoxO3a. Over the past decade, other transcription factors (PPARγ, Oct-1, etc.), as well as genetic, epigenetic, and posttranscriptional processes, have emerged as crucial contributors to the regulation of catalase expression. Altered expression levels of catalase have been reported in cancer tissues compared to their normal counterparts. Deciphering the molecular mechanisms that regulate catalase expression could, therefore, be of crucial importance for the future development of pro-oxidant cancer chemotherapy. Copyright © 2015. Published by Elsevier Inc.

Regulation of water balance in mangroves

PubMed Central

Reef, Ruth; Lovelock, Catherine E.

2015-01-01

Background Mangroves are a group of highly salt-tolerant woody plants. The high water use efficiency of mangroves under saline conditions suggests that regulation of water transport is a crucial component of their salinity tolerance. Scope This review focuses on the processes that contribute to the ability of mangroves to maintain water uptake and limit water loss to the soil and the atmosphere under saline conditions, from micro to macro scales. These processes include: (1) efficient filtering of the incoming water to exclude salt; (2) maintenance of internal osmotic potentials lower than that of the rhizosphere; (3) water-saving properties; and (4) efficient exploitation of less-saline water sources when these become available. Conclusions Mangroves are inherently plastic and can change their structure at the root, leaf and stand levels in response to salinity in order to exclude salt from the xylem stream, maintain leaf hydraulic conductance, avoid cavitation and regulate water loss (e.g. suberization of roots and alterations of leaf size, succulence and angle, hydraulic anatomy and biomass partitioning). However, much is still unknown about the regulation of water uptake in mangroves, such as how they sense and respond to heterogeneity in root zone salinity, the extent to which they utilize non-stomatally derived CO2 as a water-saving measure and whether they can exploit atmospheric water sources. PMID:25157072

The Series Connected Buck Boost Regulator Concept for High Efficiency Light Weight DC Voltage Regulation

NASA Technical Reports Server (NTRS)

Birchenough, Arthur G.

2003-01-01

Improvements in the efficiency and size of DC-DC converters have resulted from advances in components, primarily semiconductors, and improved topologies. One topology, which has shown very high potential in limited applications, is the Series Connected Boost Unit (SCBU), wherein a small DC-DC converter output is connected in series with the input bus to provide an output voltage equal to or greater than the input voltage. Since the DC-DC converter switches only a fraction of the power throughput, the overall system efficiency is very high. But this technique is limited to applications where the output is always greater than the input. The Series Connected Buck Boost Regulator (SCBBR) concept extends partial power processing technique used in the SCBU to operation when the desired output voltage is higher or lower than the input voltage, and the implementation described can even operate as a conventional buck converter to operate at very low output to input voltage ratios. This paper describes the operation and performance of an SCBBR configured as a bus voltage regulator providing 50 percent voltage regulation range, bus switching, and overload limiting, operating above 98 percent efficiency. The technique does not provide input-output isolation.

Cytological and transcriptional dynamics analysis of host plant revealed stage-specific biological processes related to compatible rice-Ustilaginoidea virens interaction.

PubMed

Chao, Jinquan; Jin, Jie; Wang, Dong; Han, Ran; Zhu, Renshan; Zhu, Yingguo; Li, Shaoqing

2014-01-01

Rice false smut, a fungal disease caused by Ustilaginoidea virens is becoming a severe detriment to rice production worldwide. However, little is known about the molecular response of rice to attacks by the smut pathogen. In this article, we define the initial infection process as having three stages: initial colonization on the pistil (stage 1, S1), amplification on the anther (stage 2, S2) and sporulation in the anther chambers (stage 3, S3). Based on the transcriptome of rice hosts in response to U. virens in two separate years, we identified 126, 204, and 580 specific regulated genes in their respective stages S1, S2, and S3, respectively, by excluding common expression patterns in other openly biotic/abiotic databases using bioinformatics. As the disease progresses, several stage-specific biological processes (BP) terms were distinctively enriched: "Phosphorylation" in stage S1, "PCD" in S2, and "Cell wall biogenesis" in S3, implying a concise signal cascade indicative of the tactics that smut pathogens use to control host rice cells during infection. 113 regulated genes were coexpressed among the three stages. They shared highly conserved promoter cis-element in the promoters in response to the regulation of WRKY and Myb for up-regulation, and ABA and Ca2+ for down regulation, indicating their potentially critical roles in signal transduction during rice-U. virens interaction. We further analyzed seven highly regulated unique genes; four were specific to pollen development, implying that pollen-related genes play critical roles in the establishment of rice susceptibility to U. virens. To my knowledge, this is the first report about probing of molecular response of rice to smut pathogen infection, which will greatly expand our understanding of the molecular events surrounding infection by rice false smut.

The four key characteristics of interpersonal emotion regulation.

PubMed

Niven, Karen

2017-10-01

Emotion researchers are increasingly interested in processes by which people influence others' feelings. Although one such process, interpersonal emotion regulation, has received particular attention in recent years, there remains confusion about exactly how to define this process. The present article aims to distinguish interpersonal emotion regulation from other, related processes by outlining its four key characteristics. Specifically, interpersonal emotion regulation is presented as a process of (i) regulation, that (ii) has an affective target, (iii) is deliberate, and (iv) has a social target. Considering these characteristics raises questions for future research concerning factors that may influence the process of interpersonal emotion regulation, why interpersonal emotion regulation sometimes fails, and whether interventions can improve people's use of interpersonal emotion regulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Kinases Involved in Both Autophagy and Mitosis.

PubMed

Li, Zhiyuan; Zhang, Xin

2017-08-31

Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis. Here in this review, we will discuss kinases that were originally identified to be involved in only one of either mitosis or autophagy, but were later found to participate in both processes, such as CDKs (cyclin-dependent kinases), Aurora kinases, PLK-1 (polo-like kinase 1), BUB1 (budding uninhibited by benzimidazoles 1), MAPKs (mitogen-activated protein kinases), mTORC1 (mechanistic target of rapamycin complex 1), AMPK (AMP-activated protein kinase), PI3K (phosphoinositide-3 kinase) and protein kinase B (AKT). By focusing on kinases involved in both autophagy and mitosis, we will get a more comprehensive understanding about the reciprocal regulation between the two key cellular events, which will also shed light on their related therapeutic investigations.

Kinases Involved in Both Autophagy and Mitosis

PubMed Central

2017-01-01

Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis. Here in this review, we will discuss kinases that were originally identified to be involved in only one of either mitosis or autophagy, but were later found to participate in both processes, such as CDKs (cyclin-dependent kinases), Aurora kinases, PLK-1 (polo-like kinase 1), BUB1 (budding uninhibited by benzimidazoles 1), MAPKs (mitogen-activated protein kinases), mTORC1 (mechanistic target of rapamycin complex 1), AMPK (AMP-activated protein kinase), PI3K (phosphoinositide-3 kinase) and protein kinase B (AKT). By focusing on kinases involved in both autophagy and mitosis, we will get a more comprehensive understanding about the reciprocal regulation between the two key cellular events, which will also shed light on their related therapeutic investigations. PMID:28858266

Manipulating environmental stresses and stress tolerance of microalgae for enhanced production of lipids and value-added products-A review.

PubMed

Chen, Bailing; Wan, Chun; Mehmood, Muhammad Aamer; Chang, Jo-Shu; Bai, Fengwu; Zhao, Xinqing

2017-11-01

Microalgae have promising potential to produce lipids and a variety of high-value chemicals. Suitable stress conditions such as nitrogen starvation and high salinity could stimulate synthesis and accumulation of lipids and high-value products by microalgae, therefore, various stress-modification strategies were developed to manipulate and optimize cultivation processes to enhance bioproduction efficiency. On the other hand, advancements in omics-based technologies have boosted the research to globally understand microalgal gene regulation under stress conditions, which enable further improvement of production efficiency via genetic engineering. Moreover, integration of multi-omics data, synthetic biology design, and genetic engineering manipulations exhibits a tremendous potential in the betterment of microalgal biorefinery. This review discusses the process manipulation strategies and omics studies on understanding the regulation of metabolite biosynthesis under various stressful conditions, and proposes genetic engineering of microalgae to improve bioproduction via manipulating stress tolerance. Copyright © 2017 Elsevier Ltd. All rights reserved.

On the role of the chaperonin CCT in the just-in-time assembly process of APC/CCdc20.

PubMed

Dekker, Carien

2010-02-05

The just-in-time hypothesis relates to the assembly of large multi-protein complexes and their regulation of activation in the cell. Here I postulate that chaperonins may contribute to the timely assembly and activation of such complexes. For the case of anaphase promoting complex/cyclosome(Cdc20) assembly by the eukaryotic chaperonin chaperonin containing Tcp1 it is shown that just-in-time synthesis and chaperone-assisted folding can synergise to generate a highly regulated assembly process of a protein complex that is vital for cell cycle progression. Once dependency has been established transcriptional regulation and chaperonin-dependency may have co-evolved to safeguard the timely activation of important multi-protein complexes. 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

MIIP, a cytoskeleton regulator that blocks cell migration and invasion, delays mitosis, and suppresses tumorogenesis.

PubMed

Wang, Yingmei; Wen, Jing; Zhang, Wei

2011-02-01

The migration and invasion inhibitory protein (MIIP) was initially discovered in a yeast two-hybrid screen for proteins that interact and inhibit the migration and invasion-promoting protein insulin-like growth factor binding protein 2 (IGFBP2). Recent studies have shown that MIIP not only modulates IGFBP2 but also regulates microtubule by binding to and inhibiting HDAC6, a class 2 histone deacetylase that deacetylates α-tubulin, heat-shock protein 90 (HSP90), and cortactin. In addition, MIIP also regulates the mitosis checkpoint, another microtubule-associated process. The location of the MIIP gene in chromosomal region 1p36, a commonly deleted region in a broad spectrum of human cancers, and the observation that MIIP attenuates tumorigenesis in a mouse model suggest that it functions as a tumor-suppressor gene. This review summarizes the recent progress in characterizing this novel protein, which regulates cell migration and mitosis, two processes that rely on the highly coordinated dynamics of the microtubule and cytoskeleton systems.

The Mediator Complex and Lipid Metabolism.

PubMed

Zhang, Yi; Xiaoli; Zhao, Xiaoping; Yang, Fajun

2013-03-01

The precise control of gene expression is essential for all biological processes. In addition to DNA-binding transcription factors, numerous transcription cofactors contribute another layer of regulation of gene transcription in eukaryotic cells. One of such transcription cofactors is the highly conserved Mediator complex, which has multiple subunits and is involved in various biological processes through directly interacting with relevant transcription factors. Although the current understanding on the biological functions of Mediator remains incomplete, research in the past decade has revealed an important role of Mediator in regulating lipid metabolism. Such function of Mediator is dependent on specific transcription factors, including peroxisome proliferator-activated receptor-gamma (PPARγ) and sterol regulatory element-binding proteins (SREBPs), which represent the master regulators of lipid metabolism. The medical significance of these findings is apparent, as aberrant lipid metabolism is intimately linked to major human diseases, such as type 2 diabetes and cardiovascular disease. Here, we briefly review the functions and molecular mechanisms of Mediator in regulation of lipid metabolism.

Wellbeing: causes and consequences of emotion regulation in work settings.

PubMed

Zammuner, V L; Galli, C

2005-10-01

Emotion regulation processes are a crucial aspect of the working role in jobs which require employee-customer interactions: What kinds of regulation processes are activated, with what frequency, and what are their correlates and consequences are important aspects to consider because of their potential implications for the well-being of individuals. To investigate these issues, a set of studies was carried out with Italian workers (N=769) performing service jobs in different sectors. Job-related, socio-demographic, and individual psychological variables were taken into account. The results confirmed the hypothesis that in service job-roles emotional labour (EL) is a component whose negative and positive implications for employees' well-being need to be considered. Emotional labour, embedded in a net of relationships with such job variables as frequency and duration of client-interaction, can result in high psychological costs for service workers. In particular, surface acting regulation was found to have a personal cost, indexed by the burnout dimensions of emotional exhaustion and depersonalization.

Self-regulation and quality of life in high-functioning young adults with autism.

PubMed

Dijkhuis, Renee R; Ziermans, Tim B; Van Rijn, Sophie; Staal, Wouter G; Swaab, Hanna

2017-10-01

Autism is generally associated with poor functional outcome but little is known about predictors of quality of life, especially during early adulthood. This study was conducted to assess subjective quality of life during early adulthood in high-functioning autism spectrum disorder and its relation with self-regulating abilities. Individuals with high-functioning autism spectrum disorder who progressed into post-secondary higher education ( N = 75) were compared to a typical peer control group ( N = 28) based on behavioral self-report questionnaires. The results indicated that individuals with high-functioning autism spectrum disorder reported significantly lower subjective quality of life than typical controls ( p < 0.001, effect size ( d) = 1.84). In addition, individuals with high-functioning autism spectrum disorder reported more problems with emotion processing ( p < 0.05, effect size ( d) = 0.79) and daily executive functioning ( p < 0.001, effect size ( d) = 1.29) than controls. A higher level of executive functioning problems was related to lower quality of life in the high-functioning autism spectrum disorder group, but no significant relation between level of emotion processing and subjective quality of life became apparent in the regression analysis. Our findings show that even in high-functioning young adults with autism, executive functioning, emotion processing, and subjective quality of life are low compared to typically developing peers. Furthermore, these results emphasize the importance of targeting executive functioning problems in individuals with autism to improve subjective quality of life.

Student Motivations as Predictors of High-Level Cognitions in Project-Based Classrooms

ERIC Educational Resources Information Center

Stolk, Jonathan; Harari, Janie

2014-01-01

It is well established that active learning helps students engage in high-level thinking strategies and develop improved cognitive skills. Motivation and self-regulated learning research, however, illustrates that cognitive engagement is an effortful process that is related to students' valuing of the learning tasks, adoption of internalized goal…

Regulated transport into the nucleus of herpesviridae DNA replication core proteins.

PubMed

Gualtiero, Alvisi; Jans, David A; Camozzi, Daria; Avanzi, Simone; Loregian, Arianna; Ripalti, Alessandro; Palù, Giorgio

2013-09-16

The Herpesvirdae family comprises several major human pathogens belonging to three distinct subfamilies. Their double stranded DNA genome is replicated in the nuclei of infected cells by a number of host and viral products. Among the latter the viral replication complex, whose activity is strictly required for viral replication, is composed of six different polypeptides, including a two-subunit DNA polymerase holoenzyme, a trimeric primase/helicase complex and a single stranded DNA binding protein. The study of herpesviral DNA replication machinery is extremely important, both because it provides an excellent model to understand processes related to eukaryotic DNA replication and it has important implications for the development of highly needed antiviral agents. Even though all known herpesviruses utilize very similar mechanisms for amplification of their genomes, the nuclear import of the replication complex components appears to be a heterogeneous and highly regulated process to ensure the correct spatiotemporal localization of each protein. The nuclear transport process of these enzymes is controlled by three mechanisms, typifying the main processes through which protein nuclear import is generally regulated in eukaryotic cells. These include cargo post-translational modification-based recognition by the intracellular transporters, piggy-back events allowing coordinated nuclear import of multimeric holoenzymes, and chaperone-assisted nuclear import of specific subunits. In this review we summarize these mechanisms and discuss potential implications for the development of antiviral compounds aimed at inhibiting the Herpesvirus life cycle by targeting nuclear import of the Herpesvirus DNA replicating enzymes.

Brief report: Academic amotivation in light of the dark side of identity formation.

PubMed

Cannard, Christine; Lannegrand-Willems, Lyda; Safont-Mottay, Claire; Zimmermann, Grégoire

2016-02-01

The study intended to determine motivational profiles of first-year undergraduates and aimed their characterization in terms of identity processes. First, a cluster analysis revealed five motivational profiles: combined (i.e., high quantity of motivation, low amotivation); intrinsic (i.e., high intrinsic, low introjected and external regulation, low amotivation); "demotivated" (i.e., very low quantity of motivation and amotivation); extrinsic (i.e., high extrinsic and identified regulation and low intrinsic and amotivation); and "amotivated" (i.e., low intrinsic and identified, very high amotivation). Second, using Lebart's (2000) methodology, the most characteristic identity processes were listed for each motivational cluster. Demotivated and amotivated profiles were refined in terms of adaptive and maladaptive forms of exploration. Notably, exploration in breadth and in depth were underrepresented in demotivated students compared to the total sample; commitment and ruminative exploration were under and overrepresented respectively in amotivated students. Educational and clinical implications are proposed and future research is suggested. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

High-Throughput, Motility-Based Sorter for Microswimmers such as C. elegans

PubMed Central

Yuan, Jinzhou; Zhou, Jessie; Raizen, David M.; Bau, Haim H.

2015-01-01

Animal motility varies with genotype, disease, aging, and environmental conditions. In many studies, it is desirable to carry out high throughput motility-based sorting to isolate rare animals for, among other things, forward genetic screens to identify genetic pathways that regulate phenotypes of interest. Many commonly used screening processes are labor-intensive, lack sensitivity, and require extensive investigator training. Here, we describe a sensitive, high throughput, automated, motility-based method for sorting nematodes. Our method is implemented in a simple microfluidic device capable of sorting thousands of animals per hour per module, and is amenable to parallelism. The device successfully enriches for known C. elegans motility mutants. Furthermore, using this device, we isolate low-abundance mutants capable of suppressing the somnogenic effects of the flp-13 gene, which regulates C. elegans sleep. By performing genetic complementation tests, we demonstrate that our motility-based sorting device efficiently isolates mutants for the same gene identified by tedious visual inspection of behavior on an agar surface. Therefore, our motility-based sorter is capable of performing high throughput gene discovery approaches to investigate fundamental biological processes. PMID:26008643

Working memory training improves emotion regulation ability: Evidence from HRV.

PubMed

Xiu, Lichao; Zhou, Renlai; Jiang, Yihan

2016-03-01

Emotion regulation during social situations plays a pivotal role in health and interpersonal functioning. In this study, we propose a working memory training approach to improve emotion regulation ability. This training promotes an updating function that is a crucial modulated process for emotion regulation. In the present study, the participants in the training group completed a running memory task over 20 days of training. Their working memory capability and high-frequency heart rate variability (HF-HRV) data on pretest and posttest were assessed and analyzed. Compared with the control group, the training group's reaction time in the 2-back working memory task was reduced significantly. In addition, the HF-HRV in the emotion regulation condition was increased after the 20-day training, which indicates that the working memory training effect could transfer to emotion regulation. In other words, working memory training improved emotion regulation ability. Copyright © 2015 Elsevier Inc. All rights reserved.

Modify the Histone to Win the Battle: Chromatin Dynamics in Plant–Pathogen Interactions

PubMed Central

Ramirez-Prado, Juan S.; Piquerez, Sophie J. M.; Bendahmane, Abdelhafid; Hirt, Heribert; Raynaud, Cécile; Benhamed, Moussa

2018-01-01

Relying on an immune system comes with a high energetic cost for plants. Defense responses in these organisms are therefore highly regulated and fine-tuned, permitting them to respond pertinently to the attack of a microbial pathogen. In recent years, the importance of the physical modification of chromatin, a highly organized structure composed of genomic DNA and its interacting proteins, has become evident in the research field of plant–pathogen interactions. Several processes, including DNA methylation, changes in histone density and variants, and various histone modifications, have been described as regulators of various developmental and defense responses. Herein, we review the state of the art in the epigenomic aspects of plant immunity, focusing on chromatin modifications, chromatin modifiers, and their physiological consequences. In addition, we explore the exciting field of understanding how plant pathogens have adapted to manipulate the plant epigenomic regulation in order to weaken their immune system and thrive in their host, as well as how histone modifications in eukaryotic pathogens are involved in the regulation of their virulence. PMID:29616066

MicroRNA-Mediated Down-Regulation of M-CSF Receptor Contributes to Maturation of Mouse Monocyte-Derived Dendritic Cells

PubMed Central

Riepsaame, Joey; van Oudenaren, Adri; den Broeder, Berlinda J. H.; van IJcken, Wilfred F. J.; Pothof, Joris; Leenen, Pieter J. M.

2013-01-01

Dendritic cell (DC) maturation is a tightly regulated process that requires coordinated and timed developmental cues. Here we investigate whether microRNAs are involved in this process. We identify microRNAs in mouse GM-CSF-generated, monocyte-related DC (GM-DC) that are differentially expressed during both spontaneous and LPS-induced maturation and characterize M-CSF receptor (M-CSFR), encoded by the Csf1r gene, as a key target for microRNA-mediated regulation in the final step toward mature DC. MicroRNA-22, -34a, and -155 are up-regulated in mature MHCIIhi CD86hi DC and mediate Csf1r mRNA and protein down-regulation. Experimental inhibition of Csf1r-targeting microRNAs in vitro results not only in sustained high level M-CSFR protein expression but also in impaired DC maturation upon stimulation by LPS. Accordingly, over-expression of Csf1r in GM-DC inhibits terminal differentiation. Taken together, these results show that developmentally regulated microRNAs control Csf1r expression, supplementing previously identified mechanisms that regulate its transcription and protein surface expression. Furthermore, our data indicate a novel function for Csf1r in mouse monocyte-derived DC, showing that down-regulation of M-CSFR expression is essential for final DC maturation. PMID:24198819

Redox regulation of neuronal voltage-gated calcium channels.

PubMed

Todorovic, Slobodan M; Jevtovic-Todorovic, Vesna

2014-08-20

Voltage-gated calcium channels are ubiquitously expressed in neurons and are key regulators of cellular excitability and synaptic transmitter release. There is accumulating evidence that multiple subtypes of voltage-gated calcium channels may be regulated by oxidation and reduction. However, the redox mechanisms involved in the regulation of channel function are not well understood. Several studies have established that both T-type and high-voltage-activated subtypes of voltage-gated calcium channel can be redox-regulated. This article reviews different mechanisms that can be involved in redox regulation of calcium channel function and their implication in neuronal function, particularly in pain pathways and thalamic oscillation. A current critical issue in the field is to decipher precise mechanisms of calcium channel modulation via redox reactions. In this review we discuss covalent post-translational modification via oxidation of cysteine molecules and chelation of trace metals, and reactions involving nitric oxide-related molecules and free radicals. Improved understanding of the roles of redox-based reactions in regulation of voltage-gated calcium channels may lead to improved understanding of novel redox mechanisms in physiological and pathological processes. Identification of redox mechanisms and sites on voltage-gated calcium channel may allow development of novel and specific ion channel therapies for unmet medical needs. Thus, it may be possible to regulate the redox state of these channels in treatment of pathological process such as epilepsy and neuropathic pain.

Computational Systems Biology Approach Predicts Regulators and Targets of microRNAs and Their Genomic Hotspots in Apoptosis Process.

PubMed

Alanazi, Ibrahim O; Ebrahimie, Esmaeil

2016-07-01

Novel computational systems biology tools such as common targets analysis, common regulators analysis, pathway discovery, and transcriptomic-based hotspot discovery provide new opportunities in understanding of apoptosis molecular mechanisms. In this study, after measuring the global contribution of microRNAs in the course of apoptosis by Affymetrix platform, systems biology tools were utilized to obtain a comprehensive view on the role of microRNAs in apoptosis process. Network analysis and pathway discovery highlighted the crosstalk between transcription factors and microRNAs in apoptosis. Within the transcription factors, PRDM1 showed the highest upregulation during the course of apoptosis, with more than 9-fold expression increase compared to non-apoptotic condition. Within the microRNAs, MIR1208 showed the highest expression in non-apoptotic condition and downregulated by more than 6 fold during apoptosis. Common regulators algorithm showed that TNF receptor is the key upstream regulator with a high number of regulatory interactions with the differentially expressed microRNAs. BCL2 and AKT1 were the key downstream targets of differentially expressed microRNAs. Enrichment analysis of the genomic locations of differentially expressed microRNAs led us to the discovery of chromosome bands which were highly enriched (p < 0.01) with the apoptosis-related microRNAs, such as 13q31.3, 19p13.13, and Xq27.3 This study opens a new avenue in understanding regulatory mechanisms and downstream functions in the course of apoptosis as well as distinguishing genomic-enriched hotspots for apoptosis process.

Cognitive regulation of smoking behavior within a cigarette: Automatic and nonautomatic processes.

PubMed

Motschman, Courtney A; Tiffany, Stephen T

2016-06-01

There has been limited research on cognitive processes governing smoking behavior in individuals who are tobacco dependent. In a replication (Baxter & Hinson, 2001) and extension, this study examined the theory (Tiffany, 1990) that drug use may be controlled by automatic processes that develop over repeated use. Heavy and occasional cigarette smokers completed a button-press reaction time (RT) task while concurrently smoking a cigarette, pretending to smoke a lit cigarette, or not smoking. Slowed RT during the button-press task indexed the cognitive disruption associated with nonautomatic control of behavior. Occasional smokers' RTs were slowed when smoking or pretending to smoke compared with when not smoking. Heavy smokers' RTs were slowed when pretending to smoke versus not smoking; however, their RTs were similarly fast when smoking compared with not smoking. The results indicated that smoking behavior was more highly regulated by controlled, nonautomatic processes among occasional smokers and by automatic processes among heavy smokers. Patterns of RT across the interpuff interval indicated that occasional smokers were significantly slowed in anticipation of and immediately after puffing onset, whereas heavy smokers were only slowed significantly after puffing onset. These findings suggest that the entirety of the smoking sequence becomes automatized, with the behaviors leading up to puffing becoming more strongly regulated by automatic processes with experience. These results have relevance to theories on the cognitive regulation of cigarette smoking and support the importance of interventions that focus on routinized behaviors that individuals engage in during and leading up to drug use. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Phosphoproteomics profiling of human skin fibroblast cells reveals pathways and proteins affected by low doses of ionizing radiation.

PubMed

Yang, Feng; Waters, Katrina M; Miller, John H; Gritsenko, Marina A; Zhao, Rui; Du, Xiuxia; Livesay, Eric A; Purvine, Samuel O; Monroe, Matthew E; Wang, Yingchun; Camp, David G; Smith, Richard D; Stenoien, David L

2010-11-30

High doses of ionizing radiation result in biological damage; however, the precise relationships between long-term health effects, including cancer, and low-dose exposures remain poorly understood and are currently extrapolated using high-dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose-dependent responses to radiation. We have identified 7117 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts 1 h post-exposure. Semi-quantitative label-free analyses were performed to identify phosphopeptides that are apparently altered by radiation exposure. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation-responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatic analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role for MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provide a basis for the systems-level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low-dose radiation exposure on human health.

Phosphoproteomics Profiling of Human Skin Fibroblast Cells Reveals Pathways and Proteins Affected by Low Doses of Ionizing Radiation

PubMed Central

Yang, Feng; Waters, Katrina M.; Miller, John H.; Gritsenko, Marina A.; Zhao, Rui; Du, Xiuxia; Livesay, Eric A.; Purvine, Samuel O.; Monroe, Matthew E.; Wang, Yingchun; Camp, David G.; Smith, Richard D.; Stenoien, David L.

2010-01-01

Background High doses of ionizing radiation result in biological damage; however, the precise relationships between long-term health effects, including cancer, and low-dose exposures remain poorly understood and are currently extrapolated using high-dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose-dependent responses to radiation. Principal Findings We have identified 7117 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts 1 h post-exposure. Semi-quantitative label-free analyses were performed to identify phosphopeptides that are apparently altered by radiation exposure. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation-responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatic analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role for MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Conclusions Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provide a basis for the systems-level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low-dose radiation exposure on human health. PMID:21152398

Structure and Function of the 26S Proteasome.

PubMed

Bard, Jared A M; Goodall, Ellen A; Greene, Eric R; Jonsson, Erik; Dong, Ken C; Martin, Andreas

2018-06-20

As the endpoint for the ubiquitin-proteasome system, the 26S proteasome is the principal proteolytic machine responsible for regulated protein degradation in eukaryotic cells. The proteasome's cellular functions range from general protein homeostasis and stress response to the control of vital processes such as cell division and signal transduction. To reliably process all the proteins presented to it in the complex cellular environment, the proteasome must combine high promiscuity with exceptional substrate selectivity. Recent structural and biochemical studies have shed new light on the many steps involved in proteasomal substrate processing, including recognition, deubiquitination, and ATP-driven translocation and unfolding. In addition, these studies revealed a complex conformational landscape that ensures proper substrate selection before the proteasome commits to processive degradation. These advances in our understanding of the proteasome's intricate machinery set the stage for future studies on how the proteasome functions as a major regulator of the eukaryotic proteome.

Quo vadis plant hormone analysis?

PubMed

Tarkowská, Danuše; Novák, Ondřej; Floková, Kristýna; Tarkowski, Petr; Turečková, Veronika; Grúz, Jiří; Rolčík, Jakub; Strnad, Miroslav

2014-07-01

Plant hormones act as chemical messengers in the regulation of myriads of physiological processes that occur in plants. To date, nine groups of plant hormones have been identified and more will probably be discovered. Furthermore, members of each group may participate in the regulation of physiological responses in planta both alone and in concert with members of either the same group or other groups. The ideal way to study biochemical processes involving these signalling molecules is 'hormone profiling', i.e. quantification of not only the hormones themselves, but also their biosynthetic precursors and metabolites in plant tissues. However, this is highly challenging since trace amounts of all of these substances are present in highly complex plant matrices. Here, we review advances, current trends and future perspectives in the analysis of all currently known plant hormones and the associated problems of extracting them from plant tissues and separating them from the numerous potentially interfering compounds.

Inhibition of Ape1 Redox Activity Promotes Odonto/osteogenic Differentiation of Dental Papilla Cells.

PubMed

Chen, Tian; Liu, Zhi; Sun, Wenhua; Li, Jingyu; Liang, Yan; Yang, Xianrui; Xu, Yang; Yu, Mei; Tian, Weidong; Chen, Guoqing; Bai, Ding

2015-12-07

Dentinogenesis is the formation of dentin, a substance that forms the majority of teeth, and this process is performed by odontoblasts. Dental papilla cells (DPCs), as the progenitor cells of odontoblasts, undergo the odontogenic differentiation regulated by multiple cytokines and paracrine signal molecules. Ape1 is a perfect paradigm of the function complexity of a biological macromolecule with two major functional regions for DNA repair and redox regulation, respectively. To date, it remains unclear whether Ape1 can regulate the dentinogenesis in DPCs. In the present study, we firstly examed the spatio-temporal expression of Ape1 during tooth germ developmental process, and found the Ape1 expression was initially high and then gradually reduced along with the tooth development. Secondly, the osteo/odontogenic differentiation capacity of DPCs was up-regulated when treated with either Ape1-shRNA or E3330 (a specific inhibitor of the Ape1 redox function), respectively. Moreover, we found that the canonical Wnt signaling pathway was activated in this process, and E3330 reinforced-osteo/odontogenic differentiation capacity was suppressed by Dickkopf1 (DKK1), a potent antagonist of canonical Wnt signaling pathway. Taken together, we for the first time showed that inhibition of Ape1 redox regulation could promote the osteo/odontogenic differentiation capacity of DPCs via canonical Wnt signaling pathway.

Redox Regulation of the Superoxide Dismutases SOD3 and SOD2 in the Pulmonary Circulation.

PubMed

Hernandez-Saavedra, Daniel; Swain, Kalin; Tuder, Rubin; Petersen, Steen V; Nozik-Grayck, Eva

2017-01-01

When evaluating the role of redox-regulating signaling in pulmonary vascular diseases, it is intriguing to consider the modulation of key antioxidant enzymes like superoxide dismutase (SOD) because SOD isoforms are regulated by redox reactions, and, in turn, modulate downstream redox sensitive processes. The emerging field of redox biology is built upon understanding the regulation and consequences of tightly controlled and specific reduction-oxidation reactions that are critical for diverse cellular processes including cell signaling. Of relevance, both the site of production of specific reactive oxygen and nitrogen species and the site of the antioxidant defenses are highly compartmentalized within the cell. For example, superoxide is generated during oxidative phosphorylation in the mitochondria as well as by a number of enzymatic sources within the cytosol and at the cell membrane. In the pulmonary circulation, these sources include the mitochondrial electron transport chain, NADPH oxidases (NOX1-4, Duox1,2), nitric oxide synthases, and xanthine oxidase; this important topic has been thoroughly reviewed recently [1]. In parallel with these different cellular sites of superoxide production, the three SOD isoforms are also specifically localized to the cytosol (SOD1), mitochondria (SOD2) or extracellular compartment (SOD3). This chapter focuses on the role of redox mechanisms regulating SOD2 and SOD3, with an emphasis on these processes in the setting of pulmonary hypertension.

The bromodomain protein BRD4 regulates splicing during heat shock.

PubMed

Hussong, Michelle; Kaehler, Christian; Kerick, Martin; Grimm, Christina; Franz, Alexandra; Timmermann, Bernd; Welzel, Franziska; Isensee, Jörg; Hucho, Tim; Krobitsch, Sylvia; Schweiger, Michal R

2017-01-09

The cellular response to heat stress is an ancient and evolutionarily highly conserved defence mechanism characterised by the transcriptional up-regulation of cyto-protective genes and a partial inhibition of splicing. These features closely resemble the proteotoxic stress response during tumor development. The bromodomain protein BRD4 has been identified as an integral member of the oxidative stress as well as of the inflammatory response, mainly due to its role in the transcriptional regulation process. In addition, there are also several lines of evidence implicating BRD4 in the splicing process. Using RNA-sequencing we found a significant increase in splicing inhibition, in particular intron retentions (IR), following heat treatment in BRD4-depleted cells. This leads to a decrease of mRNA abundancy of the affected transcripts, most likely due to premature termination codons. Subsequent experiments revealed that BRD4 interacts with the heat shock factor 1 (HSF1) such that under heat stress BRD4 is recruited to nuclear stress bodies and non-coding SatIII RNA transcripts are up-regulated. These findings implicate BRD4 as an important regulator of splicing during heat stress. Our data which links BRD4 to the stress induced splicing process may provide novel mechanisms of BRD4 inhibitors in regard to anti-cancer therapies. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

De novo transcriptome sequencing and customized abscission zone-specific microarray as a new molecular tool for analysis of tomato organ abscission

USDA-ARS?s Scientific Manuscript database

Abscission, which is the process of organ separation, is a highly regulated process occurring as a final stage of organ development. In the tomato (Solanum lycopersicum) system, flower and leaf abscission was induced by flower removal or leaf deblading, leading to auxin depletion which results in in...

Qualitative Information in Annual Reports & the Detection of Corporate Fraud: A Natural Language Processing Perspective

ERIC Educational Resources Information Center

Goel, Sunita

2009-01-01

High profile cases of fraudulent financial reporting such as those that occurred at Enron and WorldCom have shaken public confidence in the U.S. financial reporting process and have raised serious concerns about the roles of auditors, regulators, and analysts in financial reporting. In order to address these concerns and restore public confidence,…

Balancing competition for resources with multiple pest regulation in diversified agroecosystems: a process-based approach to reconcile diversification and productivity.

PubMed

Poeydebat, Charlotte; Carval, Dominique; de Lapeyre de Bellaire, Luc; Tixier, Philippe

2016-12-01

Agroecosystem plant diversification can enhance pest biological regulation and is a promising alternative to pesticide application. However, the costs of competition for resources between plants may exceed the benefits gained by pest regulation. To disentangle the interactions between pest regulation and competition, we developed a generic process-based approach that accounts for the effects of an associated plant and leaf and root pests on biomass production. We considered three crop-plant associations that differ in competition profiles, and we simulated biomass production under wide ranges of both pest regulation rates and resources' availability. We analyzed outputs to quantify the pest regulation service level that would be required to attain monoculture yield and other production goals. Results showed that pest regulation requirements were highly dependent on the profile of resource interception of the associated plant and on resources' availability. Pest regulation and the magnitude of competition between plants interacted in determining the balance between nitrogen and radiation uptake by the crop. Our findings suggest that productivity of diversified agroecosystems relative to monoculture should be optimized by assembling plants whose characteristics balance crops' resource acquisition. The theoretical insights from our study draw generic rules for vegetation assemblage to optimize trade-offs between pest regulation and production. Our findings and approach may have implications in understanding, theorizing and implementing agroecosystem diversification. By its generic and adaptable structure, our approach should be useful for studying the effects of diversification in many agroecosystems.

Systematic Genetic Screen for Transcriptional Regulators of the Candida albicans White-Opaque Switch

PubMed Central

Lohse, Matthew B.; Ene, Iuliana V.; Craik, Veronica B.; Hernday, Aaron D.; Mancera, Eugenio; Morschhäuser, Joachim; Bennett, Richard J.; Johnson, Alexander D.

2016-01-01

The human fungal pathogen Candida albicans can reversibly switch between two cell types named “white” and “opaque,” each of which is stable through many cell divisions. These two cell types differ in their ability to mate, their metabolic preferences and their interactions with the mammalian innate immune system. A highly interconnected network of eight transcriptional regulators has been shown to control switching between these two cell types. To identify additional regulators of the switch, we systematically and quantitatively measured white–opaque switching rates of 196 strains, each deleted for a specific transcriptional regulator. We identified 19 new regulators with at least a 10-fold effect on switching rates and an additional 14 new regulators with more subtle effects. To investigate how these regulators affect switching rates, we examined several criteria, including the binding of the eight known regulators of switching to the control region of each new regulatory gene, differential expression of the newly found genes between cell types, and the growth rate of each mutant strain. This study highlights the complexity of the transcriptional network that regulates the white–opaque switch and the extent to which switching is linked to a variety of metabolic processes, including respiration and carbon utilization. In addition to revealing specific insights, the information reported here provides a foundation to understand the highly complex coupling of white–opaque switching to cellular physiology. PMID:27280690

Transcription Factors in Long-Term Memory and Synaptic Plasticity

PubMed Central

Alberini, Cristina M.

2013-01-01

Transcription is a molecular requisite for long-term synaptic plasticity and long-term memory formation. Thus, in the last several years, one main interest of molecular neuroscience has been the identification of families of transcription factors that are involved in both of these processes. Transcription is a highly regulated process that involves the combined interaction and function of chromatin and many other proteins, some of which are essential for the basal process of transcription, while others control the selective activation or repression of specific genes. These regulated interactions ultimately allow a sophisticated response to multiple environmental conditions, as well as control of spatial and temporal differences in gene expression. Evidence based on correlative changes in expression, genetic mutations, and targeted molecular inhibition of gene expression have shed light on the function of transcription in both synaptic plasticity and memory formation. This review provides a brief overview of experimental work showing that several families of transcription factors, including CREB, C/EBP, Egr, AP-1, and Rel have essential functions in both processes. The results of this work suggest that patterns of transcription regulation represent the molecular signatures of long-term synaptic changes and memory formation. PMID:19126756

Functional overlap of top-down emotion regulation and generation: an fMRI study identifying common neural substrates between cognitive reappraisal and cognitively generated emotions.

PubMed

Otto, Benjamin; Misra, Supriya; Prasad, Aditya; McRae, Kateri

2014-09-01

One factor that influences the success of emotion regulation is the manner in which the regulated emotion was generated. Recent research has suggested that reappraisal, a top-down emotion regulation strategy, is more effective in decreasing self-reported negative affect when emotions were generated from the top-down, versus the bottom-up. On the basis of a process overlap framework, we hypothesized that the neural regions active during reappraisal would overlap more with emotions that were generated from the top-down, rather than from the bottom-up. In addition, we hypothesized that increased neural overlap between reappraisal and the history effects of top-down emotion generation would be associated with increased reappraisal success. The results of several analyses suggested that reappraisal and emotions that were generated from the top-down share a core network of prefrontal, temporal, and cingulate regions. This overlap is specific; no such overlap was observed between reappraisal and emotions that were generated in a bottom-up fashion. This network consists of regions previously implicated in linguistic processing, cognitive control, and self-relevant appraisals, which are processes thought to be crucial to both reappraisal and top-down emotion generation. Furthermore, individuals with high reappraisal success demonstrated greater neural overlap between reappraisal and the history of top-down emotion generation than did those with low reappraisal success. The overlap of these key regions, reflecting overlapping processes, provides an initial insight into the mechanism by which generation history may facilitate emotion regulation.

Comparative Proteomic Analysis of the Graft Unions in Hickory (Carya cathayensis) Provides Insights into Response Mechanisms to Grafting Process

PubMed Central

Xu, Dongbin; Yuan, Huwei; Tong, Yafei; Zhao, Liang; Qiu, Lingling; Guo, Wenbin; Shen, Chenjia; Liu, Hongjia; Yan, Daoliang; Zheng, Bingsong

2017-01-01

Hickory (Carya cathayensis), a tree with high nutritional and economic value, is widely cultivated in China. Grafting greatly reduces the juvenile phase length and makes the large scale cultivation of hickory possible. To reveal the response mechanisms of this species to grafting, we employed a proteomics-based approach to identify differentially expressed proteins in the graft unions during the grafting process. Our study identified 3723 proteins, of which 2518 were quantified. A total of 710 differentially expressed proteins (DEPs) were quantified and these were involved in various molecular functional and biological processes. Among these DEPs, 341 were up-regulated and 369 were down-regulated at 7 days after grafting compared with the control. Four auxin-related proteins were down-regulated, which was in agreement with the transcription levels of their encoding genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the ‘Flavonoid biosynthesis’ pathway and ‘starch and sucrose metabolism’ were both significantly up-regulated. Interestingly, five flavonoid biosynthesis-related proteins, a flavanone 3-hyfroxylase, a cinnamate 4-hydroxylase, a dihydroflavonol-4-reductase, a chalcone synthase, and a chalcone isomerase, were significantly up-regulated. Further experiments verified a significant increase in the total flavonoid contents in scions, which suggests that graft union formation may activate flavonoid biosynthesis to increase the content of a series of downstream secondary metabolites. This comprehensive analysis provides fundamental information on the candidate proteins and secondary metabolism pathways involved in the grafting process for hickory. PMID:28496455

The regulatory network of ThbZIP1 in response to abscisic acid treatment

PubMed Central

Ji, Xiaoyu; Liu, Guifeng; Liu, Yujia; Nie, Xianguang; Zheng, Lei; Wang, Yucheng

2015-01-01

Previously, a bZIP transcription factor from Tamarix hispida, ThbZIP1, was characterized: plants overexpressing ThbZIP1 displayed improved salt stress tolerance but were sensitive to abscisic acid (ABA). In the current study, we further characterized the regulatory network of ThbZIP1 and the mechanism of ABA sensitivity mediated by ThbZIP1. An ABF transcription factor from T. hispida, ThABF1, directly regulates the expression of ThbZIP1. Microarray analysis identified 1662 and 1609 genes that were respectively significantly upregulated or downregulated by ThbZIP1 when exposed to ABA. Gene ontology (GO) analysis showed that the processes including “response to stimulus,” “catalytic activity,” “binding function,” and “metabolic process” were highly altered in ThbZIP1 expressing plants exposed to ABA. The gene expression in ThbZIP1 transformed plants were compared between exposed to ABA and salt on the genome scale. Genes differentially regulated by both salt and ABA treatment only accounted for 9.75% of total differentially regulated genes. GO analysis showed that structural molecule activity, organelle part, membrane-enclosed lumen, reproduction, and reproductive process are enhanced by ABA but inhibited by salt stress. Conversely, immune system and multi-organism process were improved by salt but inhibited by ABA. Transcription regulator activity, enzyme regulator activity, and developmental process were significantly altered by ABA but were not affected by salt stress. Our study provides insights into how ThbZIP1 mediates ABA and salt stress response at the molecular level. PMID:25713576

A dynamic intron retention program enriched in RNA processing genes regulates gene expression during terminal erythropoiesis

DOE PAGES

Pimentel, Harold; Parra, Marilyn; Gee, Sherry L.; ...

2015-11-03

Differentiating erythroblasts execute a dynamic alternative splicing program shown here to include extensive and diverse intron retention (IR) events. Cluster analysis revealed hundreds of developmentallydynamic introns that exhibit increased IR in mature erythroblasts, and are enriched in functions related to RNA processing such as SF3B1 spliceosomal factor. Distinct, developmentally-stable IR clusters are enriched in metal-ion binding functions and include mitoferrin genes SLC25A37 and SLC25A28 that are critical for iron homeostasis. Some IR transcripts are abundant, e.g. comprising ~50% of highly-expressed SLC25A37 and SF3B1 transcripts in late erythroblasts, and thereby limiting functional mRNA levels. IR transcripts tested were predominantly nuclearlocalized. Splicemore » site strength correlated with IR among stable but not dynamic intron clusters, indicating distinct regulation of dynamically-increased IR in late erythroblasts. Retained introns were preferentially associated with alternative exons with premature termination codons (PTCs). High IR was observed in disease-causing genes including SF3B1 and the RNA binding protein FUS. Comparative studies demonstrated that the intron retention program in erythroblasts shares features with other tissues but ultimately is unique to erythropoiesis. Finally, we conclude that IR is a multi-dimensional set of processes that post-transcriptionally regulate diverse gene groups during normal erythropoiesis, misregulation of which could be responsible for human disease.« less

A dynamic intron retention program enriched in RNA processing genes regulates gene expression during terminal erythropoiesis

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

Pimentel, Harold; Parra, Marilyn; Gee, Sherry L.

Differentiating erythroblasts execute a dynamic alternative splicing program shown here to include extensive and diverse intron retention (IR) events. Cluster analysis revealed hundreds of developmentallydynamic introns that exhibit increased IR in mature erythroblasts, and are enriched in functions related to RNA processing such as SF3B1 spliceosomal factor. Distinct, developmentally-stable IR clusters are enriched in metal-ion binding functions and include mitoferrin genes SLC25A37 and SLC25A28 that are critical for iron homeostasis. Some IR transcripts are abundant, e.g. comprising ~50% of highly-expressed SLC25A37 and SF3B1 transcripts in late erythroblasts, and thereby limiting functional mRNA levels. IR transcripts tested were predominantly nuclearlocalized. Splicemore » site strength correlated with IR among stable but not dynamic intron clusters, indicating distinct regulation of dynamically-increased IR in late erythroblasts. Retained introns were preferentially associated with alternative exons with premature termination codons (PTCs). High IR was observed in disease-causing genes including SF3B1 and the RNA binding protein FUS. Comparative studies demonstrated that the intron retention program in erythroblasts shares features with other tissues but ultimately is unique to erythropoiesis. Finally, we conclude that IR is a multi-dimensional set of processes that post-transcriptionally regulate diverse gene groups during normal erythropoiesis, misregulation of which could be responsible for human disease.« less

Highly accessible AU-rich regions in 3' untranslated regions are hotspots for binding of regulatory factors.

PubMed

Plass, Mireya; Rasmussen, Simon H; Krogh, Anders

2017-04-01

Post-transcriptional regulation is regarded as one of the major processes involved in the regulation of gene expression. It is mainly performed by RNA binding proteins and microRNAs, which target RNAs and typically affect their stability. Recent efforts from the scientific community have aimed at understanding post-transcriptional regulation at a global scale by using high-throughput sequencing techniques such as cross-linking and immunoprecipitation (CLIP), which facilitates identification of binding sites of these regulatory factors. However, the diversity in the experimental procedures and bioinformatics analyses has hindered the integration of multiple datasets and thus limited the development of an integrated view of post-transcriptional regulation. In this work, we have performed a comprehensive analysis of 107 CLIP datasets from 49 different RBPs in HEK293 cells to shed light on the complex interactions that govern post-transcriptional regulation. By developing a more stringent CLIP analysis pipeline we have discovered the existence of conserved regulatory AU-rich regions in the 3'UTRs where miRNAs and RBPs that regulate several processes such as polyadenylation or mRNA stability bind. Analogous to promoters, many factors have binding sites overlapping or in close proximity in these hotspots and hence the regulation of the mRNA may depend on their relative concentrations. This hypothesis is supported by RBP knockdown experiments that alter the relative concentration of RBPs in the cell. Upon AGO2 knockdown (KD), transcripts containing "free" target sites show increased expression levels compared to those containing target sites in hotspots, which suggests that target sites within hotspots are less available for miRNAs to bind. Interestingly, these hotspots appear enriched in genes with regulatory functions such as DNA binding and RNA binding. Taken together, our results suggest that hotspots are functional regulatory elements that define an extra layer of regulation of post-transcriptional regulatory networks.

Highly accessible AU-rich regions in 3’ untranslated regions are hotspots for binding of regulatory factors

PubMed Central

2017-01-01

Post-transcriptional regulation is regarded as one of the major processes involved in the regulation of gene expression. It is mainly performed by RNA binding proteins and microRNAs, which target RNAs and typically affect their stability. Recent efforts from the scientific community have aimed at understanding post-transcriptional regulation at a global scale by using high-throughput sequencing techniques such as cross-linking and immunoprecipitation (CLIP), which facilitates identification of binding sites of these regulatory factors. However, the diversity in the experimental procedures and bioinformatics analyses has hindered the integration of multiple datasets and thus limited the development of an integrated view of post-transcriptional regulation. In this work, we have performed a comprehensive analysis of 107 CLIP datasets from 49 different RBPs in HEK293 cells to shed light on the complex interactions that govern post-transcriptional regulation. By developing a more stringent CLIP analysis pipeline we have discovered the existence of conserved regulatory AU-rich regions in the 3’UTRs where miRNAs and RBPs that regulate several processes such as polyadenylation or mRNA stability bind. Analogous to promoters, many factors have binding sites overlapping or in close proximity in these hotspots and hence the regulation of the mRNA may depend on their relative concentrations. This hypothesis is supported by RBP knockdown experiments that alter the relative concentration of RBPs in the cell. Upon AGO2 knockdown (KD), transcripts containing “free” target sites show increased expression levels compared to those containing target sites in hotspots, which suggests that target sites within hotspots are less available for miRNAs to bind. Interestingly, these hotspots appear enriched in genes with regulatory functions such as DNA binding and RNA binding. Taken together, our results suggest that hotspots are functional regulatory elements that define an extra layer of regulation of post-transcriptional regulatory networks. PMID:28410363

pH measurement and a rational and practical pH control strategy for high throughput cell culture system.

PubMed

Zhou, Haiying; Purdie, Jennifer; Wang, Tongtong; Ouyang, Anli

2010-01-01

The number of therapeutic proteins produced by cell culture in the pharmaceutical industry continues to increase. During the early stages of manufacturing process development, hundreds of clones and various cell culture conditions are evaluated to develop a robust process to identify and select cell lines with high productivity. It is highly desirable to establish a high throughput system to accelerate process development and reduce cost. Multiwell plates and shake flasks are widely used in the industry as the scale down model for large-scale bioreactors. However, one of the limitations of these two systems is the inability to measure and control pH in a high throughput manner. As pH is an important process parameter for cell culture, this could limit the applications of these scale down model vessels. An economical, rapid, and robust pH measurement method was developed at Eli Lilly and Company by employing SNARF-4F 5-(-and 6)-carboxylic acid. The method demonstrated the ability to measure the pH values of cell culture samples in a high throughput manner. Based upon the chemical equilibrium of CO(2), HCO(3)(-), and the buffer system, i.e., HEPES, we established a mathematical model to regulate pH in multiwell plates and shake flasks. The model calculates the required %CO(2) from the incubator and the amount of sodium bicarbonate to be added to adjust pH to a preset value. The model was validated by experimental data, and pH was accurately regulated by this method. The feasibility of studying the pH effect on cell culture in 96-well plates and shake flasks was also demonstrated in this study. This work shed light on mini-bioreactor scale down model construction and paved the way for cell culture process development to improve productivity or product quality using high throughput systems. Copyright 2009 American Institute of Chemical Engineers

The role of symmetry in the regulation of brain dynamics

NASA Astrophysics Data System (ADS)

Tang, Evelyn; Giusti, Chad; Cieslak, Matthew; Grafton, Scott; Bassett, Danielle

Synchronous neural processes regulate a wide range of behaviors from attention to learning. Yet structural constraints on these processes are far from understood. We draw on new theoretical links between structural symmetries and the control of synchronous function, to offer a reconceptualization of the relationships between brain structure and function in human and non-human primates. By classifying 3-node motifs in macaque connectivity data, we find the most prevalent motifs can theoretically ensure a diversity of function including strict synchrony as well as control to arbitrary states. The least prevalent motifs are theoretically controllable to arbitrary states, which may not be desirable in a biological system. In humans, regions with high topological similarity of connections (a continuous notion related to symmetry) are most commonly found in fronto-parietal systems, which may account for their critical role in cognitive control. Collectively, our work underscores the role of symmetry and topological similarity in regulating dynamics of brain function.

N-cadherin prodomain processing regulates synaptogenesis.

PubMed

Reinés, Analía; Bernier, Louis-Philippe; McAdam, Robyn; Belkaid, Wiam; Shan, Weisong; Koch, Alexander W; Séguéla, Philippe; Colman, David R; Dhaunchak, Ajit S

2012-05-02

Classical cadherins, which are adhesion molecules functioning at the CNS synapse, are synthesized as adhesively inactive precursor proteins in the endoplasmic reticulum (ER). Signal sequence and prodomain cleavage in the ER and Golgi apparatus, respectively, activates their adhesive properties. Here, we provide the first evidence for sorting of nonadhesive precursor N-cadherin (ProN) to the neuronal surface, where it coexists with adhesively competent mature N-cadherin (N-cad), generating a spectrum of adhesive strengths. In cultured hippocampal neurons, a high ProN/N-cad ratio downregulates synapse formation. Neurons expressing genetically engineered uncleavable ProN make markedly fewer synapses. The synapse number can be rescued to normality by depleting surface ProN levels through prodomain cleavage by an exogenous protease. Finally, prodomain processing is developmentally regulated in the rat hippocampus. We conclude that it is the ProN/N-cad ratio and not mature N-cad alone that is critical for regulation of adhesion during synaptogenesis.

Neuroticism and responsiveness to error feedback: adaptive self-regulation versus affective reactivity.

PubMed

Robinson, Michael D; Moeller, Sara K; Fetterman, Adam K

2010-10-01

Responsiveness to negative feedback has been seen as functional by those who emphasize the value of reflecting on such feedback in self-regulating problematic behaviors. On the other hand, the very same responsiveness has been viewed as dysfunctional by its link to punishment sensitivity and reactivity. The present 4 studies, involving 203 undergraduate participants, sought to reconcile such discrepant views in the context of the trait of neuroticism. In cognitive tasks, individuals were given error feedback when they made mistakes. It was found that greater tendencies to slow down following error feedback were associated with higher levels of accuracy at low levels of neuroticism but lower levels of accuracy at high levels of neuroticism. Individual differences in neuroticism thus appear crucial in understanding whether behavioral alterations following negative feedback reflect proactive versus reactive mechanisms and processes. Implications for understanding the processing basis of neuroticism and adaptive self-regulation are discussed.

Learning Boolean Networks in HepG2 cells using ToxCast High-Content Imaging Data (SOT annual meeting)

EPA Science Inventory

Cells adapt to their environment via homeostatic processes that are regulated by complex molecular networks. Our objective was to learn key elements of these networks in HepG2 cells using ToxCast High-content imaging (HCI) measurements taken over three time points (1, 24, and 72h...

Behavioral and molecular studies of quantitative differences in hygienic behavior in honeybees.

PubMed

Gempe, Tanja; Stach, Silke; Bienefeld, Kaspar; Otte, Marianne; Beye, Martin

2016-10-21

Hygienic behavior (HB) enables honeybees to tolerate parasites, including infection with the parasitic mite Varroa destructor, and it is a well-known example of a quantitative genetic trait. The understanding of the molecular processes underpinning the quantitative differences in this behavior remains limited. We performed gene expression studies in worker bees that displayed quantitative genetic differences in HB. We established a high and low genetic source of HB performance and studied the engagements into HB of single worker bees under the same environmental conditions. We found that the percentage of worker bees that engaged in a hygienic behavioral task tripled in the high versus low HB sources, thus suggesting that genetic differences may mediate differences in stimulated states to perform HB. We found 501 differently expressed genes (DEGs) in the brains of hygienic and non-hygienic performing workers in the high HB source bees, and 342 DEGs in the brains of hygienic performing worker bees, relative to the gene expression in non-hygienic worker bees from the low HB source group. "Cell surface receptor ligand signal transduction" in the high and "negative regulation of cell communication" in the low HB source were overrepresented molecular processes, suggesting that these molecular processes in the brain may play a role in the regulation of quantitative differences in HB. Moreover, only 21 HB-associated DEGs were common between the high and low HB sources. The better HB colony performance is primarily achieved by a high number of bees engaging in the hygienic tasks that associate with distinct molecular processes in the brain. We propose that different gene products and pathways may mediate the quantitative genetic differences of HB.

mir-30d Regulates multiple genes in the autophagy pathway and impairs autophagy process in human cancer cells

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

Yang, Xiaojun; Department of General Surgery, Gansu Provincial Hospital, Lanzhou, Gansu 710000; Zhong, Xiaomin

2013-02-15

Highlights: ► Gene set enrichment analysis indicated mir-30d might regulate the autophagy pathway. ► mir-30d represses the expression of BECN1, BNIP3L, ATG12, ATG5 and ATG2. ► BECN1, BNIP3L, ATG12, ATG5 and ATG2 are direct targets of mir-30d. ► mir-30d inhibits autophagosome formation and LC3B-I conversion to LC3B-II. ► mir-30d regulates the autophagy process. -- Abstract: In human epithelial cancers, the microRNA (miRNA) mir-30d is amplified with high frequency and serves as a critical oncomir by regulating metastasis, apoptosis, proliferation, and differentiation. Autophagy, a degradation pathway for long-lived protein and organelles, regulates the survival and death of many cell types. Increasingmore » evidence suggests that autophagy plays an important function in epithelial tumor initiation and progression. Using a combined bioinformatics approach, gene set enrichment analysis, and miRNA target prediction, we found that mir-30d might regulate multiple genes in the autophagy pathway including BECN1, BNIP3L, ATG12, ATG5, and ATG2. Our further functional experiments demonstrated that the expression of these core proteins in the autophagy pathway was directly suppressed by mir-30d in cancer cells. Finally, we showed that mir-30d regulated the autophagy process by inhibiting autophagosome formation and LC3B-I conversion to LC3B-II. Taken together, our results provide evidence that the oncomir mir-30d impairs the autophagy process by targeting multiple genes in the autophagy pathway. This result will contribute to understanding the molecular mechanism of mir-30d in tumorigenesis and developing novel cancer therapy strategy.« less

Effects of single cortisol administrations on human affect reviewed: Coping with stress through adaptive regulation of automatic cognitive processing.

PubMed

Putman, Peter; Roelofs, Karin

2011-05-01

The human stress hormone cortisol may facilitate effective coping after psychological stress. In apparent agreement, administration of cortisol has been demonstrated to reduce fear in response to stressors. For anxious patients with phobias or posttraumatic stress disorder this has been ascribed to hypothetical inhibition of retrieval of traumatic memories. However, such stress-protective effects may also work via adaptive regulation of early cognitive processing of threatening information from the environment. This paper selectively reviews the available literature on effects of single cortisol administrations on affect and early cognitive processing of affectively significant information. The concluded working hypothesis is that immediate effects of high concentration of cortisol may facilitate stress-coping via inhibition of automatic processing of goal-irrelevant threatening information and through increased automatic approach-avoidance responses in early emotional processing. Limitations in the existing literature and suggestions for future directions are briefly discussed. Copyright © 2010 Elsevier Ltd. All rights reserved.

Direct and efficient xylitol production from xylan by Saccharomyces cerevisiae through transcriptional level and fermentation processing optimizations.

PubMed

Li, Zhe; Qu, Hongnan; Li, Chun; Zhou, Xiaohong

2013-12-01

In this study, four engineered Saccharomyces cerevisiae carrying xylanase, β-xylosidase and xylose reductase genes by different transcriptional regulations were constructed to directly convert xylan to xylitol. According to the results, the high-copy number plasmid required a rigid selection for promoter characteristics, on the contrast, the selection of promoters could be more flexible for low-copy number plasmid. For cell growth and xylitol production, glucose and galactose were found more efficient than other sugars. The semi-aerobic condition and feeding of co-substrates were taken to improve the yield of xylitol. It was found that the strain containing high-copy number plasmid had the highest xylitol yield, but it was sensitive to the change of fermentation. However, the strain carrying low-copy number plasmid was more adaptable to different processes. By optimization of the transcriptional regulation and fermentation processes, the xylitol concentration could be increased of 1.7 folds and the yield was 0.71 g xylitol/g xylan. Copyright © 2013 Elsevier Ltd. All rights reserved.

High-Performance Liquid Chromatography (HPLC)-Based Detection and Quantitation of Cellular c-di-GMP.

PubMed

Petrova, Olga E; Sauer, Karin

2017-01-01

The modulation of c-di-GMP levels plays a vital role in the regulation of various processes in a wide array of bacterial species. Thus, investigation of c-di-GMP regulation requires reliable methods for the assessment of c-di-GMP levels and turnover. Reversed-phase high-performance liquid chromatography (RP-HPLC) analysis has become a commonly used approach to accomplish these goals. The following describes the extraction and HPLC-based detection and quantification of c-di-GMP from Pseudomonas aeruginosa samples, a procedure that is amenable to modifications for the analysis of c-di-GMP in other bacterial species.

Implication of Ca2+ in the regulation of replicative life span of budding yeast.

PubMed

Tsubakiyama, Ryohei; Mizunuma, Masaki; Gengyo, Anri; Yamamoto, Josuke; Kume, Kazunori; Miyakawa, Tokichi; Hirata, Dai

2011-08-19

In eukaryotic cells, Ca(2+)-triggered signaling pathways are used to regulate a wide variety of cellular processes. Calcineurin, a highly conserved Ca(2+)/calmodulin-dependent protein phosphatase, plays key roles in the regulation of diverse biological processes in organisms ranging from yeast to humans. We isolated a mutant of the SIR3 gene, implicated in the regulation of life span, as a suppressor of the Ca(2+) sensitivity of zds1Δ cells in the budding yeast Saccharomyces cerevisiae. Therefore, we investigated a relationship between Ca(2+) signaling and life span in yeast. Here we show that Ca(2+) affected the replicative life span (RLS) of yeast. Increased external and intracellular Ca(2+) levels caused a reduction in their RLS. Consistently, the increase in calcineurin activity by either the zds1 deletion or the constitutively activated calcineurin reduced RLS. Indeed, the shortened RLS of zds1Δ cells was suppressed by the calcineurin deletion. Further, the calcineurin deletion per se promoted aging without impairing the gene silencing typically observed in short-lived sir mutants, indicating that calcineurin plays an important role in a regulation of RLS even under normal growth condition. Thus, our results indicate that Ca(2+) homeostasis/Ca(2+) signaling are required to regulate longevity in budding yeast.

Characterization of nicotine binding to the rat brain P/sub 2/ preparation: the identification of multiple binding sites which include specific up-regulatory site(s)

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

Sloan, J.W.

1984-01-01

These studies show that nicotine binds to the rat brain P/sub 2/ preparation by saturable and reversible processes. Multiple binding sites were revealed by the configuration of saturation, kinetic and Scatchard plots. A least squares best fit of Scatchard data using nonlinear curve fitting programs confirmed the presence of a very high affinity site, an up-regulatory site, a high affinity site and one or two low affinity sites. Stereospecificity was demonstrated for the up-regulatory site where (+)-nicotine was more effective and for the high affinity site where (-)-nicotine had a higher affinity. Drugs which selectively up-regulate nicotine binding site(s) havemore » been identified. Further, separate very high and high affinity sites were identified for (-)- and (+)-(/sup 3/H)nicotine, based on evidence that the site density for the (-)-isomer is 10 times greater than that for the (+)-isomer at these sites. Enhanced nicotine binding has been shown to be a statistically significant phenomenon which appears to be a consequence of drugs binding to specific site(s) which up-regulate binding at other site(s). Although Scatchard and Hill plots indicate positive cooperatively, up-regulation more adequately describes the function of these site(s). A separate up-regulatory site is suggested by the following: (1) Drugs vary markedly in their ability to up-regulate binding. (2) Both the affinity and the degree of up-regulation can be altered by structural changes in ligands. (3) Drugs with specificity for up-regulation have been identified. (4) Some drugs enhance binding in a dose-related manner. (5) Competition studies employing cold (-)- and (+)-nicotine against (-)- and (+)-(/sup 3/H)nicotine show that the isomers bind to separate sites which up-regulate binding at the (-)- and (+)-nicotine high affinity sites and in this regard (+)-nicotine is more specific and efficacious than (-)-nicotine.« less

A Guide to Ordinary High Water Mark (OHWM) Delineation for Non-Perennial Streams in the Western Mountains, Valleys, and Coast Region of the United States

DTIC Science & Technology

2014-08-01

in vegetation characteristics. This guide addresses the underlying hydrologic and geomorphic concepts per- taining to the OHWM and the field...temporally varying hydrologic and geomorphic processes .............................. 12 4 The distribution of rankings for each of the three primary...define, amend, or replace any existing regulations, laws , or legal guidance related to the OHWM or to the regulation of WoUS. Furthermore, determining

Identification of the key regulating genes of diminished ovarian reserve (DOR) by network and gene ontology analysis.

PubMed

Pashaiasl, Maryam; Ebrahimi, Mansour; Ebrahimie, Esmaeil

2016-09-01

Diminished ovarian reserve (DOR) is one of the reasons for infertility that not only affects both older and young women. Ovarian reserve assessment can be used as a new prognostic tool for infertility treatment decision making. Here, up- and down-regulated gene expression profiles of granulosa cells were analysed to generate a putative interaction map of the involved genes. In addition, gene ontology (GO) analysis was used to get insight intol the biological processes and molecular functions of involved proteins in DOR. Eleven up-regulated genes and nine down-regulated genes were identified and assessed by constructing interaction networks based on their biological processes. PTGS2, CTGF, LHCGR, CITED, SOCS2, STAR and FSTL3 were the key nodes in the up-regulated networks, while the IGF2, AMH, GREM, and FOXC1 proteins were key in the down-regulated networks. MIRN101-1, MIRN153-1 and MIRN194-1 inhibited the expression of SOCS2, while CSH1 and BMP2 positively regulated IGF1 and IGF2. Ossification, ovarian follicle development, vasculogenesis, sequence-specific DNA binding transcription factor activity, and golgi apparatus are the major differential groups between up-regulated and down-regulated genes in DOR. Meta-analysis of publicly available transcriptomic data highlighted the high coexpression of CTGF, connective tissue growth factor, with the other key regulators of DOR. CTGF is involved in organ senescence and focal adhesion pathway according to GO analysis. These findings provide a comprehensive system biology based insight into the aetiology of DOR through network and gene ontology analyses.

Characterization of the Methylation Status of Pax7 and Myogenic Regulator Factors in Cell Myogenic Differentiation.

PubMed

Chao, Zhe; Zheng, Xin-Li; Sun, Rui-Ping; Liu, Hai-Long; Huang, Li-Li; Cao, Zong-Xi; Deng, Chang-Yan; Wang, Feng

2016-07-01

Epigenetic processes in the development of skeletal muscle have been appreciated for over a decade. DNA methylation is a major epigenetic modification important for regulating gene expression and suppressing spurious transcription. Up to now, the importance of epigenetic marks in the regulation of Pax7 and myogenic regulatory factors (MRFs) expression is far less explored. In the present study, semi-quantitative the real-time polymerase chain reaction (RT-PCR) analyses showed MyoD and Myf5 were expressed in activated and quiescent C2C12 cells. MyoG was expressed in a later stage of myogenesis. Pax7 was weakly expressed in differentiated C2C12 cells. To further understand the regulation of expression of these genes, the DNA methylation status of Pax7, MyoD, and Myf5 was determined by bisulfite sequencing PCR. During the C2C12 myoblasts fusion process, the changes of promoter and exon 1 methylation of Pax7, MyoD, and Myf5 genes were observed. In addition, an inverse relationship of low methylation and high expression was found. These results suggest that DNA methylation may be an important mechanism regulating Pax7 and MRFs transcription in cell myogenic differentiation.

Talking with the Public about Regulating High-level Waste Disposal: Recent Progress

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

Kotra, J. P.; Leslie, B. W.

Increasing public confidence in the U.S. Nuclear Regulatory Commission (NRC) as an effective and independent regulator is an explicit goal of the Agency (1). Consistent with long-established mechanisms and procedures, NRC provides the public access to its decision-making process. Recently, during the course of a rulemaking required by statute, NRC examined its means for inviting public access as well as the NRC staff's effectiveness in furthering public confidence in it's actions as a regulator. When developing new, site-specific regulations for the proposed geologic repository at Yucca Mountain, Nevada, NRC's Division of Waste Management found it necessary to adapt and improvemore » its efforts to inform and involve the public in NRC's decision making process. Major changes were made to the way in which technical staff prepare for speaking to general audiences. The format used for public meetings was modified to encourage dialogue with participants. Handout and presentation materials that explain NRC's role and technical topics of concern in plain language were developed and are regularly updated. NRC successfully applied these and other institutional changes as it completed final regulations for Yucca Mountain and while developing and introducing a draft license review plan for public comment.« less

Manifestations of metacognitive activity during the collaborative planning of chemistry practical investigations

NASA Astrophysics Data System (ADS)

Mathabathe, Kgadi Clarrie; Potgieter, Marietjie

2017-07-01

This paper elaborates a process followed to characterise manifestations of cognitive regulation during the collaborative planning of chemistry practical investigations. Metacognitive activity was defined as the demonstration of planning, monitoring, control and evaluation of cognitive activities by students while carrying out the chemistry task. Inherent in collaborative learning is the social aspect of metacognition, which in this study was evidenced in social cognitive regulation (notably of intra- and interpersonal metacognitive regulations) as groups of students went about planning their practical investigations. Discussions of two of the learning groups (n = 4; n = 3) as they planned the extended practical investigation were recorded, transcribed and analysed for indicators of any inherent metacognitive activity. The process of characterising the manifestations of metacognition resulted in the development of a coding system which specifies not only the regulatory strategies at play but the type of regulation (self or other), the area of regulation (cognition, task performance or behaviour) as well as the depth of regulatory contributions (high or low). The fine-grained coding system allowed for a finer theoretical elucidation of the social nature of metacognition. The implications of this study for metacognition and chemistry education research are highlighted.

Regulating Cortical Neurodynamics for Past, Present and Future

NASA Astrophysics Data System (ADS)

Liljenström, Hans

2002-09-01

Behaving systems, biological as well as artificial, need to respond quickly and accurately to changes in the environment. The response is dependent on stored memories, and novel situations should be learnt for the guidance of future behavior. A highly nonlinear system dynamics is required in order to cope with a complex and changing environment, and this dynamics should be regulated to match the demands of the current situation, and to predict future behavior. In many cases the dynamics should be regulated to minimize processing time. We use computer simulations of cortical structures in order to investigate how the neurodynamics of these systems can be regulated for optimal performance in an unknown and changing environment. In particular, we study how cortical oscillations can serve to amplify weak signals and sustain an input pattern for more accurate information processing, and how chaotic-like behavior could increase the sensitivity in initial, exploratory states. We mimic regulating mechanisms based on neuromodulators, intrinsic noise levels, and various synchronizing effects. We find optimal noise levels where system performance is maximized, and neuromodulatory strategies for an efficient pattern recognition, where the anticipatory state of the system plays an important role.

Quantitative phosphoproteomic analysis of caprine muscle with high and low meat quality.

PubMed

Liu, Manshun; Wei, Yanchao; Li, Xin; Quek, Siew Young; Zhao, Jing; Zhong, Huazhen; Zhang, Dequan; Liu, Yongfeng

2018-07-01

During the conversion of muscle to meat, protein phosphorylation can regulate various biological processes that have important effects on meat quality. To investigate the phosphorylation pattern of protein on rigor mortis, goat longissimus thoracis and external intercostals were classified into two groups (high quality and low quality), and meat quality was evaluated according to meat quality attributes (Warner-Bratzler shear force, Color, pH and drip loss). A quantitative mass spectrometry-based phosphoproteomic study was conducted to analyze the caprine muscle at 12h postmortem applying the TiO 2 -SIMAC-HILIC (TiSH) phosphopeptide enrichment strategy. A total of 2125 phosphopeptides were identified from 750 phosphoproteins. Among them, 96 proteins had differed in phosphorylation levels. The majority of these proteins are involved in glucose metabolism and muscle contraction. The differential phosphorylation level of proteins (PFK, MYL2 and HSP27) in two groups may be the crucial factors of regulating muscle rigor mortis. This study provides a comprehensive view for the phosphorylation status of caprine muscle at rigor mortis, it also gives a better understanding of the regulation of protein phosphorylation on various biological processes that affect the final meat quality attributes. Copyright © 2018. Published by Elsevier Ltd.

Combined Effect of Levels in Personal Self-Regulation and Regulatory Teaching on Meta-Cognitive, on Meta-Motivational, and on Academic Achievement Variables in Undergraduate Students.

PubMed

de la Fuente, Jesús; Sander, Paul; Martínez-Vicente, José M; Vera, Mariano; Garzón, Angélica; Fadda, Salvattore

2017-01-01

The Theory of Self- vs . Externally-Regulated Learning™ (SRL vs. ERL) proposed different types of relationships among levels of variables in Personal Self-Regulation (PSR) and Regulatory Teaching (RT) to predict the meta-cognitive, meta-motivational and -emotional variables of learning, and of Academic Achievement in Higher Education. The aim of this investigation was empirical in order to validate the model of the combined effect of low-medium-high levels in PSR and RT on the dependent variables. For the analysis of combinations, a selected sample of 544 undergraduate students from two Spanish universities was used. Data collection was obtained from validated instruments, in Spanish versions. Using an ex-post-facto design, different Univariate and Multivariate Analyses (3 × 1, 3 × 3, and 4 × 1) were conducted. Results provide evidence for a consistent effect of low-medium-high levels of PSR and of RT, thus giving significant partial confirmation of the proposed rational model. As predicted, (1) the levels of PSR and positively and significantly effected the levels of learning approaches, resilience, engagement, academic confidence, test anxiety, and procedural and attitudinal academic achievement; (2) the most favorable type of interaction was a high level of PSR with a high level RT process. The limitations and implications of these results in the design of effective teaching are analyzed, to improve university teaching-learning processes.

Combined Effect of Levels in Personal Self-Regulation and Regulatory Teaching on Meta-Cognitive, on Meta-Motivational, and on Academic Achievement Variables in Undergraduate Students

PubMed Central

de la Fuente, Jesús; Sander, Paul; Martínez-Vicente, José M.; Vera, Mariano; Garzón, Angélica; Fadda, Salvattore

2017-01-01

The Theory of Self- vs. Externally-Regulated Learning™ (SRL vs. ERL) proposed different types of relationships among levels of variables in Personal Self-Regulation (PSR) and Regulatory Teaching (RT) to predict the meta-cognitive, meta-motivational and -emotional variables of learning, and of Academic Achievement in Higher Education. The aim of this investigation was empirical in order to validate the model of the combined effect of low-medium-high levels in PSR and RT on the dependent variables. For the analysis of combinations, a selected sample of 544 undergraduate students from two Spanish universities was used. Data collection was obtained from validated instruments, in Spanish versions. Using an ex-post-facto design, different Univariate and Multivariate Analyses (3 × 1, 3 × 3, and 4 × 1) were conducted. Results provide evidence for a consistent effect of low-medium-high levels of PSR and of RT, thus giving significant partial confirmation of the proposed rational model. As predicted, (1) the levels of PSR and positively and significantly effected the levels of learning approaches, resilience, engagement, academic confidence, test anxiety, and procedural and attitudinal academic achievement; (2) the most favorable type of interaction was a high level of PSR with a high level RT process. The limitations and implications of these results in the design of effective teaching are analyzed, to improve university teaching-learning processes. PMID:28280473

Comparative transcriptome analysis to investigate the potential role of miRNAs in milk protein/fat quality.

PubMed

Wang, Xuehui; Zhang, Li; Jin, Jing; Xia, Anting; Wang, Chunmei; Cui, Yingjun; Qu, Bo; Li, Qingzhang; Sheng, Chunyan

2018-04-19

miRNAs play an important role in the processes of cell differentiation, biological development, and physiology. Here we investigated the molecular mechanisms regulating milk secretion and quality in dairy cows via transcriptome analyses of mammary gland tissues from dairy cows during the high-protein/high-fat, low-protein/low-fat or dry periods. To characterize the important roles of miRNAs and mRNAs in milk quality and to elucidate their regulatory networks in relation to milk secretion and quality, an integrated analysis was performed. A total of 25 core miRNAs were found to be differentially expressed (DE) during lactation compared to non-lactation, and these miRNAs were involved in epithelial cell terminal differentiation and mammary gland development. In addition, comprehensive analysis of mRNA and miRNA expression between high-protein/high-fat group and low-protein/low-fat groups indicated that, 38 miRNAs and 944 mRNAs were differentially expressed between them. Furthermore, 38 DE miRNAs putatively negatively regulated 253 DE mRNAs. The putative genes (253 DE mRNAs) were enriched in lipid biosynthetic process and amino acid transmembrane transporter activity. Moreover, putative DE genes were significantly enriched in fatty acid (FA) metabolism, biosynthesis of amino acids, synthesis and degradation of ketone bodies and biosynthesis of unsaturated FAs. Our results suggest that DE miRNAs might play roles as regulators of milk quality and milk secretion during mammary gland differentiation.

Karrikins: Regulators Involved in Phytohormone Signaling Networks during Seed Germination and Seedling Development

PubMed Central

Meng, Yongjie; Shuai, Haiwei; Luo, Xiaofeng; Chen, Feng; Zhou, Wenguan; Yang, Wenyu; Shu, Kai

2017-01-01

Seed germination and early seedling establishment are critical stages during a plant’s life cycle. These stages are precisely regulated by multiple internal factors, including phytohormones and environmental cues such as light. As a family of small molecules discovered in wildfire smoke, karrikins (KARs) play a key role in various biological processes, including seed dormancy release, germination regulation, and seedling establishment. KARs show a high similarity with strigolactone (SL) in both chemical structure and signaling transduction pathways. Current evidence shows that KARs may regulate seed germination by mediating the biosynthesis and/or signaling transduction of abscisic acid (ABA), gibberellin (GA) and auxin [indoleacetic acid (IAA)]. Interestingly, KARs regulate seed germination differently in different species. Furthermore, the promotion effect on seedling establishment implies that KARs have a great potential application in alleviating shade avoidance response, which attracts more and more attention in plant molecular biology. In these processes, KARs may have complicated interactions with phytohormones, especially with IAA. In this updated review, we summarize the current understanding of the relationship between KARs and SL in the chemical structure, signaling pathway and the regulation of plant growth and development. Further, the crosstalk between KARs and phytohormones in regulating seed germination and seedling development and that between KARs and IAA during shade responses are discussed. Finally, future challenges and research directions for the KAR research field are suggested. PMID:28174573

Assessment of myoblast circular RNA dynamics and its correlation with miRNA during myogenic differentiation.

PubMed

Zhang, Pengpeng; Xu, Haixia; Li, Rui; Wu, Wei; Chao, Zhe; Li, Cencen; Xia, Wei; Wang, Lei; Yang, Jinzeng; Xu, Yongjie

2018-06-01

Myoblast differentiation is a highly complex process that is regulated by proteins as well as by non-coding RNAs. Circular RNAs have been identified as an emerging new class of non-coding RNA in the modulation of skeletal muscle development, whereas their expression profiles and functional regulation in myoblast differentiation remain unknown. In the present study, we performed deep RNA-sequencing of C2C12 myoblasts during cell differentiation and uncovered 37,751 unique circular RNAs derived from 6943 hosting genes. The ensuing qRT-PCR and RNA fluorescence in situ hybridization verification were carried out to confirm the RNA-sequencing results. An unbiased analysis demonstrated dynamic circular RNA expression changes in the process of myoblast differentiation, and the circular RNA abundances were independent from their cognate linear RNAs. Gene ontology analysis showed that many down-regulated circular RNAs were exclusive to cell division and the cell cycle, whereas up-regulated circular RNAs were related to the cell development process. Furthermore, interaction networks of circular RNA-microRNA were constructed. Several microRNAs well-known for myoblast regulation, such as miR-133, miR-24 and miR-23a, were in this network. In summary, this study showed that circular RNA expression dynamics changed during myoblast differentiation. Circular RNAs play a role in regulating the myoblast cell cycle and development by acting as microRNA binding sites to facilitate their regulation of gene expression during myoblast differentiation. These findings open a new avenue for future investigation of this emerging RNA class in skeletal muscle growth and development. Copyright © 2018 Elsevier Ltd. All rights reserved.

Proteomic investigation into betulinic acid-induced apoptosis of human cervical cancer HeLa cells.

PubMed

Xu, Tao; Pang, Qiuying; Zhou, Dong; Zhang, Aiqin; Luo, Shaman; Wang, Yang; Yan, Xiufeng

2014-01-01

Betulinic acid is a pentacyclic triterpenoid that exhibits anticancer functions in human cancer cells. This study provides evidence that betulinic acid is highly effective against the human cervical cancer cell line HeLa by inducing dose- and time-dependent apoptosis. The apoptotic process was further investigated using a proteomics approach to reveal protein expression changes in HeLa cells following betulinic acid treatment. Proteomic analysis revealed that there were six up- and thirty down-regulated proteins in betulinic acid-induced HeLa cells, and these proteins were then subjected to functional pathway analysis using multiple analysis software. UDP-glucose 6-dehydrogenase, 6-phosphogluconate dehydrogenase decarboxylating, chain A Horf6-a novel human peroxidase enzyme that involved in redox process, was found to be down-regulated during the apoptosis process of the oxidative stress response pathway. Consistent with our results at the protein level, an increase in intracellular reactive oxygen species was observed in betulinic acid-treated cells. The proteins glucose-regulated protein and cargo-selection protein TIP47, which are involved in the endoplasmic reticulum pathway, were up-regulated by betulinic acid treatment. Meanwhile, 14-3-3 family proteins, including 14-3-3β and 14-3-3ε, were down-regulated in response to betulinic acid treatment, which is consistent with the decrease in expression of the target genes 14-3-3β and 14-3-3ε. Furthermore, it was found that the antiapoptotic bcl-2 gene was down-regulated while the proapoptotic bax gene was up-regulated after betulinic acid treatment in HeLa cells. These results suggest that betulinic acid induces apoptosis of HeLa cells by triggering both the endoplasmic reticulum pathway and the ROS-mediated mitochondrial pathway.

Phosphate homeostasis and its role in bone health.

PubMed

Penido, Maria Goretti M G; Alon, Uri S

2012-11-01

Phosphate is one of the most abundant minerals in the body, and its serum levels are regulated by a complex set of processes occurring in the intestine, skeleton, and kidneys. The currently known main regulators of phosphate homeostasis include parathyroid hormone (PTH), calcitriol, and a number of peptides collectively known as the "phosphatonins" of which fibroblast growth factor-23 (FGF-23) has been best defined. Maintenance of extracellular and intracellular phosphate levels within a narrow range is important for many biological processes, including energy metabolism, cell signaling, regulation of protein synthesis, skeletal development, and bone integrity. The presence of adequate amounts of phosphate is critical for the process of apoptosis of mature chondrocytes in the growth plate. Without the presence of this mineral in high enough quantities, chondrocytes will not go into apoptosis, and the normal physiological chain of events that includes invasion of blood vessels and the generation of new bone will be blocked, resulting in rickets and delayed growth. In the rest of the skeleton, hypophosphatemia will result in osteomalacia due to an insufficient formation of hydroxyapatite. This review will address phosphate metabolism and its role in bone health.

Regulators of alternative polyadenylation operate at the transition from mitosis to meiosis.

PubMed

Shan, Lingjuan; Wu, Chan; Chen, Di; Hou, Lei; Li, Xin; Wang, Lixia; Chu, Xiao; Hou, Yifeng; Wang, Zhaohui

2017-02-20

In the sexually reproductive organisms, gametes are produced by meiosis following a limited mitotic amplification. However, the intrinsic program switching cells from mitotic to meiotic cycle is unclear. Alternative polyadenylation (APA) is a highly conserved means of gene regulation and is achieved by the RNA 3'-processing machinery to generate diverse 3'UTR profiles. In Drosophila spermatogenesis, we observed distinct profiles of transcriptome-wide 3'UTR between mitotic and meiotic cells. In mutant germ cells stuck in mitosis, 3'UTRs of hundreds of genes were consistently shifted. Remarkably, altering the levels of multiple 3'-processing factors disrupted germline's progression to meiosis, indicative of APA's active role in this transition. An RNA-binding protein (RBP) Tut could directly bind 3'UTRs of 3'-processing factors whose expressions were repressed in the presence of Tut-containing complex. Further, we demonstrated that this RBP complex could execute the repression post-transcriptionally by recruiting CCR4/Twin of deadenylation complex. Thus, we propose that an RBP complex regulates the dynamic APA profile to promote the mitosis-to-meiosis transition. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Self-regulation and quality of life in high-functioning young adults with autism

PubMed Central

Dijkhuis, Renee R; Ziermans, Tim B; Van Rijn, Sophie; Staal, Wouter G; Swaab, Hanna

2016-01-01

Background: Autism is generally associated with poor functional outcome but little is known about predictors of quality of life, especially during early adulthood. This study was conducted to assess subjective quality of life during early adulthood in high-functioning autism spectrum disorder and its relation with self-regulating abilities. Individuals with high-functioning autism spectrum disorder who progressed into post-secondary higher education (N = 75) were compared to a typical peer control group (N = 28) based on behavioral self-report questionnaires. The results indicated that individuals with high-functioning autism spectrum disorder reported significantly lower subjective quality of life than typical controls (p < 0.001, effect size (d) = 1.84). In addition, individuals with high-functioning autism spectrum disorder reported more problems with emotion processing (p < 0.05, effect size (d) = 0.79) and daily executive functioning (p < 0.001, effect size (d) = 1.29) than controls. A higher level of executive functioning problems was related to lower quality of life in the high-functioning autism spectrum disorder group, but no significant relation between level of emotion processing and subjective quality of life became apparent in the regression analysis. Our findings show that even in high-functioning young adults with autism, executive functioning, emotion processing, and subjective quality of life are low compared to typically developing peers. Furthermore, these results emphasize the importance of targeting executive functioning problems in individuals with autism to improve subjective quality of life. PMID:27407040

Extracellular Matrix Degradation and Remodeling in Development and Disease

PubMed Central

Lu, Pengfei; Takai, Ken; Weaver, Valerie M.; Werb, Zena

2011-01-01

The extracellular matrix (ECM) serves diverse functions and is a major component of the cellular microenvironment. The ECM is a highly dynamic structure, constantly undergoing a remodeling process where ECM components are deposited, degraded, or otherwise modified. ECM dynamics are indispensible during restructuring of tissue architecture. ECM remodeling is an important mechanism whereby cell differentiation can be regulated, including processes such as the establishment and maintenance of stem cell niches, branching morphogenesis, angiogenesis, bone remodeling, and wound repair. In contrast, abnormal ECM dynamics lead to deregulated cell proliferation and invasion, failure of cell death, and loss of cell differentiation, resulting in congenital defects and pathological processes including tissue fibrosis and cancer. Understanding the mechanisms of ECM remodeling and its regulation, therefore, is essential for developing new therapeutic interventions for diseases and novel strategies for tissue engineering and regenerative medicine. PMID:21917992

Hormone Profiling in Plant Tissues.

PubMed

Müller, Maren; Munné-Bosch, Sergi

2017-01-01

Plant hormones are for a long time known to act as chemical messengers in the regulation of physiological processes during a plant's life cycle, from germination to senescence. Furthermore, plant hormones simultaneously coordinate physiological responses to biotic and abiotic stresses. To study the hormonal regulation of physiological processes, three main approaches have been used (1) exogenous application of hormones, (2) correlative studies through measurements of endogenous hormone levels, and (3) use of transgenic and/or mutant plants altered in hormone metabolism or signaling. A plant hormone profiling method is useful to unravel cross talk between hormones and help unravel the hormonal regulation of physiological processes in studies using any of the aforementioned approaches. However, hormone profiling is still particularly challenging due to their very low abundance in plant tissues. In this chapter, a sensitive, rapid, and accurate method to quantify all the five "classic" classes of plant hormones plus other plant growth regulators, such as jasmonates, salicylic acid, melatonin, and brassinosteroids is described. The method includes a fast and simple extraction procedure without time consuming steps as purification or derivatization, followed by optimized ultrahigh-performance liquid chromatography coupled to electrospray ionization-tandem mass spectrometry (UHPLC-MS/MS) analysis. This protocol facilitates the high-throughput analysis of hormone profiling and is applicable to different plant tissues.

Decoding transcriptional enhancers: Evolving from annotation to functional interpretation

PubMed Central

Engel, Krysta L.; Mackiewicz, Mark; Hardigan, Andrew A.; Myers, Richard M.; Savic, Daniel

2016-01-01

Deciphering the intricate molecular processes that orchestrate the spatial and temporal regulation of genes has become an increasingly major focus of biological research. The differential expression of genes by diverse cell types with a common genome is a hallmark of complex cellular functions, as well as the basis for multicellular life. Importantly, a more coherent understanding of gene regulation is critical for defining developmental processes, evolutionary principles and disease etiologies. Here we present our current understanding of gene regulation by focusing on the role of enhancer elements in these complex processes. Although functional genomic methods have provided considerable advances to our understanding of gene regulation, these assays, which are usually performed on a genome-wide scale, typically provide correlative observations that lack functional interpretation. Recent innovations in genome editing technologies have placed gene regulatory studies at an exciting crossroads, as systematic, functional evaluation of enhancers and other transcriptional regulatory elements can now be performed in a coordinated, high-throughput manner across the entire genome. This review provides insights on transcriptional enhancer function, their role in development and disease, and catalogues experimental tools commonly used to study these elements. Additionally, we discuss the crucial role of novel techniques in deciphering the complex gene regulatory landscape and how these studies will shape future research. PMID:27224938

Decoding transcriptional enhancers: Evolving from annotation to functional interpretation.

PubMed

Engel, Krysta L; Mackiewicz, Mark; Hardigan, Andrew A; Myers, Richard M; Savic, Daniel

2016-09-01

Deciphering the intricate molecular processes that orchestrate the spatial and temporal regulation of genes has become an increasingly major focus of biological research. The differential expression of genes by diverse cell types with a common genome is a hallmark of complex cellular functions, as well as the basis for multicellular life. Importantly, a more coherent understanding of gene regulation is critical for defining developmental processes, evolutionary principles and disease etiologies. Here we present our current understanding of gene regulation by focusing on the role of enhancer elements in these complex processes. Although functional genomic methods have provided considerable advances to our understanding of gene regulation, these assays, which are usually performed on a genome-wide scale, typically provide correlative observations that lack functional interpretation. Recent innovations in genome editing technologies have placed gene regulatory studies at an exciting crossroads, as systematic, functional evaluation of enhancers and other transcriptional regulatory elements can now be performed in a coordinated, high-throughput manner across the entire genome. This review provides insights on transcriptional enhancer function, their role in development and disease, and catalogues experimental tools commonly used to study these elements. Additionally, we discuss the crucial role of novel techniques in deciphering the complex gene regulatory landscape and how these studies will shape future research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-inflammatory and wound healing activities of calophyllolide isolated from Calophyllum inophyllum Linn.

PubMed

Nguyen, Van-Linh; Truong, Cong-Tri; Nguyen, Binh Cao Quan; Vo, Thanh-Niem Van; Dao, Trong-Thuc; Nguyen, Van-Dan; Trinh, Dieu-Thuong Thi; Huynh, Hieu Kim; Bui, Chi-Bao

2017-01-01

Due to the high-cost and limitations of current wound healing treatments, the search for alternative approaches or drugs, particularly from medicinal plants, is of key importance. In this study, we report anti-inflammatory and wound healing activities of the major calophyllolide (CP) compound isolated from Calophyllum inophyllum Linn. The results showed that CP had no effect on HaCaT cell viability over a range of concentrations. CP reduced fibrosis formation and effectively promoted wound closure in mouse model without causing body weight loss. The underlying molecular mechanisms of wound repair by CP was investigated. CP markedly reduced MPO activity, and increased M2 macrophage skewing, as shown by up-regulation of M2-related gene expression, which is beneficial to the wound healing process. CP treatment prevented a prolonged inflammatory process by down-regulation of the pro-inflammatory cytokines-IL-1β, IL-6, TNF-α, but up-regulation of the anti-inflammatory cytokine, IL-10. This study is the first to indicate a plausible role for CP in accelerating the process of wound healing through anti-inflammatory activity mechanisms, namely, by regulation of inflammatory cytokines, reduction in MPO, and switching of macrophages to an M2 phenotype. These findings may enable the utilization of CP as a potent therapeutic for cutaneous wound healing.

The Ca2+/Calcineurin-Regulated cup Gene Family in Dictyostelium discoideum and Its Possible Involvement in Development

PubMed Central

Coukell, Barrie; Li, Yi; Moniakis, John; Cameron, Anne

2004-01-01

Changes in free intracellular Ca2+ are thought to regulate several major processes during Dictyostelium development, including cell aggregation and cell type-specific gene expression, but the mechanisms involved are unclear. To learn more about Ca2+ signaling and Ca2+ homeostasis in this organism, we used suppression subtractive hybridization to identify genes up-regulated by high extracellular Ca2+. Unexpectedly, many of the genes identified belong to a novel gene family (termed cup) with seven members. In vegetative cells, the cup genes were up-regulated by high Ca2+ but not by other ions or by heat, oxidative, or osmotic stress. cup induction by Ca2+ was blocked completely by inhibitors of calcineurin and protein synthesis. In developing cells, cup expression was high during aggregation and late development but low during the slug stage. This pattern correlates closely with reported levels of free intracellular Ca2+ during development. The cup gene products are highly homologous, acidic proteins possessing putative ricin domains. BLAST searches failed to reveal homologs in other organisms, but Western analyses suggested that Cup-like proteins might exist in certain other cellular slime mold species. Localization experiments indicated that Cup proteins are primarily cytoplasmic but become cell membrane-associated during Ca2+ stress and cell aggregation. When cup expression was down-regulated by antisense RNA, the cells failed to aggregate. However, this developmental block was overcome by partially up-regulating cup expression. Together, these results suggest that the Cup proteins in Dictyostelium might play an important role in stabilizing and/or regulating the cell membrane during Ca2+ stress and/or certain stages of development. PMID:14871937

System properties, feedback control and effector coordination of human temperature regulation.

PubMed

Werner, Jürgen

2010-05-01

The aim of human temperature regulation is to protect body processes by establishing a relative constancy of deep body temperature (regulated variable), in spite of external and internal influences on it. This is basically achieved by a distributed multi-sensor, multi-processor, multi-effector proportional feedback control system. The paper explains why proportional control implies inherent deviations of the regulated variable from the value in the thermoneutral zone. The concept of feedback of the thermal state of the body, conveniently represented by a high-weighted core temperature (T (c)) and low-weighted peripheral temperatures (T (s)) is equivalent to the control concept of "auxiliary feedback control", using a main (regulated) variable (T (c)), supported by an auxiliary variable (T (s)). This concept implies neither regulation of T (s) nor feedforward control. Steady-states result in the closed control-loop, when the open-loop properties of the (heat transfer) process are compatible with those of the thermoregulatory processors. They are called operating points or balance points and are achieved due to the inherent property of dynamical stability of the thermoregulatory feedback loop. No set-point and no comparison of signals (e.g. actual-set value) are necessary. Metabolic heat production and sweat production, though receiving the same information about the thermal state of the body, are independent effectors with different thresholds and gains. Coordination between one of these effectors and the vasomotor effector is achieved by the fact that changes in the (heat transfer) process evoked by vasomotor control are taken into account by the metabolic/sweat processor.

Hippo circuitry and the redox modulation of hippo components in cancer cell fate decisions.

PubMed

Ashraf, Asma; Pervaiz, Shazib

2015-12-01

Meticulous and precise control of organ size is undoubtedly one of the most pivotal processes in mammalian development and regeneration along with cell differentiation, morphogenesis and programmed cell death. These processes are strictly regulated by complex and highly coordinated mechanisms to maintain a steady growth state. There are a number of extrinsic and intrinsic factors that dictate the total number and/or size of cells by influencing growth, proliferation, differentiation and cell death. Multiple pathways, such as those involved in promoting organ size and others that restrict disproportionate tissue growth act simultaneously to maintain cellular and tissue homeostasis. Aberrations at any level in these organ size-regulating processes can lead to various pathological states with cancers being the most formidable one (Yin and Zhang, 2011). Extensive research in the realm of growth control has led to the identification of the Hippo-signaling pathway as a critical network in modulating tissue growth via its effect on multiple signaling pathways and through intricate crosstalk with proteins that regulate cell polarity, adhesion and cell-cell interactions (Zhao et al., 2011b). The Hippo pathway controls cell number and organ size by transducing signals from the plasma membrane to the nucleus to regulate the expression of genes involved in cell fate determination (Shi et al., 2015). In this review, we summarize the recent discoveries concerning Hippo pathway, its diversiform regulation in mammals as well as its implications in cancers, and highlight the possible role of oxidative stress in Hippo pathway regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantitative High-Throughput Screening and Orthogonal Assays to Identify Modulators of the Vitamin D Receptor (SETAC)

EPA Science Inventory

The Vitamin D nuclear receptor (VDR) is a selective, ligand-inducible transcription factor involved in numerous biological processes such as cell proliferation, differentiation, detoxification, calcium homeostasis, neurodevelopment, immune system regulation, cardiovascular functi...

Redox Regulation of Neuronal Voltage-Gated Calcium Channels

PubMed Central

Jevtovic-Todorovic, Vesna

2014-01-01

Abstract Significance: Voltage-gated calcium channels are ubiquitously expressed in neurons and are key regulators of cellular excitability and synaptic transmitter release. There is accumulating evidence that multiple subtypes of voltage-gated calcium channels may be regulated by oxidation and reduction. However, the redox mechanisms involved in the regulation of channel function are not well understood. Recent Advances: Several studies have established that both T-type and high-voltage-activated subtypes of voltage-gated calcium channel can be redox-regulated. This article reviews different mechanisms that can be involved in redox regulation of calcium channel function and their implication in neuronal function, particularly in pain pathways and thalamic oscillation. Critical Issues: A current critical issue in the field is to decipher precise mechanisms of calcium channel modulation via redox reactions. In this review we discuss covalent post-translational modification via oxidation of cysteine molecules and chelation of trace metals, and reactions involving nitric oxide-related molecules and free radicals. Improved understanding of the roles of redox-based reactions in regulation of voltage-gated calcium channels may lead to improved understanding of novel redox mechanisms in physiological and pathological processes. Future Directions: Identification of redox mechanisms and sites on voltage-gated calcium channel may allow development of novel and specific ion channel therapies for unmet medical needs. Thus, it may be possible to regulate the redox state of these channels in treatment of pathological process such as epilepsy and neuropathic pain. Antioxid. Redox Signal. 21, 880–891. PMID:24161125

[Regulatory policies on alcohol in Spain. Experience-based public health? 2008 SESPAS Report].

PubMed

Villalbí, Joan R; Granero, Lluís; Brugal, M Teresa

2008-04-01

The present article reviews the proposal for alcohol regulation made in Spain in 2006 by the Ministry of Health and Consumer Affairs and dropped a few months later as adverse positions took over the debate in the political arena and the media. The background to these regulations, as well as their components, the process, and the actors involved are analyzed, and the factors leading to this outcome are discussed. A comparison is made with the tobacco regulation initiative in 2005, which resulted in a regulatory law with a highly favorable impact on public health. The actors interested in promoting alcohol consumption and opposed to any regulation have a privileged institutional presence, generating powerful resistance. Although these regulatory proposals would have marginal impacts on their trade, wine growers and wineries have been the most visible forces against regulation and have had the greatest political and media impact. Equally, manipulated messages on the health benefits of alcohol use have fed arguments against regulation. The lack of political and media consensus in this case stands in contrast with the tobacco regulation process, in which a certain political consensus had previously been reached and the smoking prevention movement had permeated the media with preventive messages, framing the issue in terms favorable for regulation. To gain ground, the sectors interested in expanding public policies for the prevention of the harm caused by alcohol need greater cohesion and organization. Professional public health organizations can substantially contribute to this field.

Multilevel Regulation of Bacterial Gene Expression with the Combined STAR and Antisense RNA System.

PubMed

Lee, Young Je; Kim, Soo-Jung; Moon, Tae Seok

2018-03-16

Synthetic small RNA regulators have emerged as a versatile tool to predictably control bacterial gene expression. Owing to their simple design principles, small size, and highly orthogonal behavior, these engineered genetic parts have been incorporated into genetic circuits. However, efforts to achieve more sophisticated cellular functions using RNA regulators have been hindered by our limited ability to integrate different RNA regulators into complex circuits. Here, we present a combined RNA regulatory system in Escherichia coli that uses small transcription activating RNA (STAR) and antisense RNA (asRNA) to activate or deactivate target gene expression in a programmable manner. Specifically, we demonstrated that the activated target output by the STAR system can be deactivated by expressing two different types of asRNAs: one binds to and sequesters the STAR regulator, affecting the transcription process, while the other binds to the target mRNA, affecting the translation process. We improved deactivation efficiencies (up to 96%) by optimizing each type of asRNA and then integrating the two optimized asRNAs into a single circuit. Furthermore, we demonstrated that the combined STAR and asRNA system can control gene expression in a reversible way and can regulate expression of a gene in the genome. Lastly, we constructed and simultaneously tested two A AND NOT B logic gates in the same cell to show sophisticated multigene regulation by the combined system. Our approach establishes a methodology for integrating multiple RNA regulators to rationally control multiple genes.

Distant homologs of anti-apoptotic factor HAX1 encode parvalbumin-like calcium binding proteins.

PubMed

Kokoszyńska, Katarzyna; Rychlewski, Leszek; Wyrwicz, Lucjan S

2010-07-15

Apoptosis is a highly ordered and orchestrated multiphase process controlled by the numerous cellular and extra-cellular signals, which executes the programmed cell death via release of cytochrome c alterations in calcium signaling, caspase-dependent limited proteolysis and DNA fragmentation. Besides the general modifiers of apoptosis, several tissue-specific regulators of this process were identified including HAX1 (HS-1 associated protein X-1) - an anti-apoptotic factor active in myeloid cells. Although HAX1 was the subject of various experimental studies, the mechanisms of its action and a functional link connected with the regulation of apoptosis still remains highly speculative. Here we provide the data which suggests that HAX1 may act as a regulator or as a sensor of calcium. On the basis of iterative similarity searches, we identified a set of distant homologs of HAX1 in insects. The applied fold recognition protocol gives us strong evidence that the distant insects' homologs of HAX1 are novel parvalbumin-like calcium binding proteins. Although the whole three EF-hands fold is not preserved in vertebrate our analysis suggests that there is an existence of a potential single EF-hand calcium binding site in HAX1. The molecular mechanism of its action remains to be identified, but the risen hypothesis easily translates into previously reported lines of various data on the HAX1 biology as well as, provides us a direct link to the regulation of apoptosis. Moreover, we also report that other family of myeloid specific apoptosis regulators - myeloid leukemia factors (MLF1, MLF2) share the homologous C-terminal domain and taxonomic distribution with HAX1. Performed structural and active sites analyses gave new insights into mechanisms of HAX1 and MLF families in apoptosis process and suggested possible role of HAX1 in calcium-binding, still the analyses require further experimental verification.

Distant homologs of anti-apoptotic factor HAX1 encode parvalbumin-like calcium binding proteins

PubMed Central

2010-01-01

Background Apoptosis is a highly ordered and orchestrated multiphase process controlled by the numerous cellular and extra-cellular signals, which executes the programmed cell death via release of cytochrome c alterations in calcium signaling, caspase-dependent limited proteolysis and DNA fragmentation. Besides the general modifiers of apoptosis, several tissue-specific regulators of this process were identified including HAX1 (HS-1 associated protein X-1) - an anti-apoptotic factor active in myeloid cells. Although HAX1 was the subject of various experimental studies, the mechanisms of its action and a functional link connected with the regulation of apoptosis still remains highly speculative. Findings Here we provide the data which suggests that HAX1 may act as a regulator or as a sensor of calcium. On the basis of iterative similarity searches, we identified a set of distant homologs of HAX1 in insects. The applied fold recognition protocol gives us strong evidence that the distant insects' homologs of HAX1 are novel parvalbumin-like calcium binding proteins. Although the whole three EF-hands fold is not preserved in vertebrate our analysis suggests that there is an existence of a potential single EF-hand calcium binding site in HAX1. The molecular mechanism of its action remains to be identified, but the risen hypothesis easily translates into previously reported lines of various data on the HAX1 biology as well as, provides us a direct link to the regulation of apoptosis. Moreover, we also report that other family of myeloid specific apoptosis regulators - myeloid leukemia factors (MLF1, MLF2) share the homologous C-terminal domain and taxonomic distribution with HAX1. Conclusions Performed structural and active sites analyses gave new insights into mechanisms of HAX1 and MLF families in apoptosis process and suggested possible role of HAX1 in calcium-binding, still the analyses require further experimental verification. PMID:20633251

Neprilysin and Aβ Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer’s Disease

PubMed Central

Grimm, Marcus O. W.; Mett, Janine; Stahlmann, Christoph P.; Haupenthal, Viola J.; Zimmer, Valerie C.; Hartmann, Tobias

2013-01-01

One of the characteristic hallmarks of Alzheimer’s disease (AD) is an accumulation of amyloid β (Aβ) leading to plaque formation and toxic oligomeric Aβ complexes. Besides the de novo synthesis of Aβ caused by amyloidogenic processing of the amyloid precursor protein (APP), Aβ levels are also highly dependent on Aβ degradation. Several enzymes are described to cleave Aβ. In this review we focus on one of the most prominent Aβ degrading enzymes, the zinc-metalloprotease Neprilysin (NEP). In the first part of the review we discuss beside the general role of NEP in Aβ degradation the alterations of the enzyme observed during normal aging and the progression of AD. In vivo and cell culture experiments reveal that a decreased NEP level results in an increased Aβ level and vice versa. In a pathological situation like AD, it has been reported that NEP levels and activity are decreased and it has been suggested that certain polymorphisms in the NEP gene result in an increased risk for AD. Conversely, increasing NEP activity in AD mouse models revealed an improvement in some behavioral tests. Therefore it has been suggested that increasing NEP might be an interesting potential target to treat or to be protective for AD making it indispensable to understand the regulation of NEP. Interestingly, it is discussed that the APP intracellular domain (AICD), one of the cleavage products of APP processing, which has high similarities to Notch receptor processing, might be involved in the transcriptional regulation of NEP. However, the mechanisms of NEP regulation by AICD, which might be helpful to develop new therapeutic strategies, are up to now controversially discussed and summarized in the second part of this review. In addition, we review the impact of AICD not only in the transcriptional regulation of NEP but also of further genes. PMID:24391587

Role of mineralization inhibitors in the regulation of hard tissue biomineralization: relevance to initial enamel formation and maturation

PubMed Central

Margolis, Henry C.; Kwak, Seo-Young; Yamazaki, Hajime

2014-01-01

Vertebrate mineralized tissues, i.e., enamel, dentin, cementum, and bone, have unique hierarchical structures and chemical compositions. Although these tissues are similarly comprised of a crystalline calcium apatite mineral phase and a protein component, they differ with respect to crystal size and shape, level and distribution of trace mineral ions, the nature of the proteins present, and their relative proportions of mineral and protein components. Despite apparent differences, mineralized tissues are similarly derived by highly concerted extracellular processes involving matrix proteins, proteases, and mineral ion fluxes that collectively regulate the nucleation, growth and organization of forming mineral crystals. Nature, however, provides multiple ways to control the onset, rate, location, and organization of mineral deposits in developing mineralized tissues. Although our knowledge is quite limited in some of these areas, recent evidence suggests that hard tissue formation is, in part, controlled through the regulation of specific molecules that inhibit the mineralization process. This paper addresses the role of mineralization inhibitors in the regulation of biological mineralization with emphasis on the relevance of current findings to the process of amelogenesis. Mineralization inhibitors can also serve to maintain driving forces for calcium phosphate precipitation and prevent unwanted mineralization. Recent evidence shows that native phosphorylated amelogenins have the capacity to prevent mineralization through the stabilization of an amorphous calcium phosphate precursor phase, as observed in vitro and in developing teeth. Based on present findings, the authors propose that the transformation of initially formed amorphous mineral deposits to enamel crystals is an active process associated with the enzymatic processing of amelogenins. Such processing may serve to control both initial enamel crystal formation and subsequent maturation. PMID:25309443

Structural Basis of Vta1 Function in the Multivesicular Body Sorting Pathway

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

Xiao, Junyu; Xia, Hengchuan; Zhou, Jiahai

The MVB pathway plays essential roles in several eukaryotic cellular processes. Proper function of the MVB pathway requires reversible membrane association of the ESCRTs, a process catalyzed by Vps4 ATPase. Vta1 regulates the Vps4 activity, but its mechanism of action was poorly understood. We report the high-resolution crystal structures of the Did2- and Vps60-binding N-terminal domain and the Vps4-binding C-terminal domain of S. cerevisiae Vta1. The C-terminal domain also mediates Vta1 dimerization and both subunits are required for its function as a Vps4 regulator. Emerging from our analysis is a mechanism of regulation by Vta1 in which the C-terminal domainmore » stabilizes the ATP-dependent double ring assembly of Vps4. In addition, the MIT motif-containing N-terminal domain, projected by a long disordered linker, allows contact between the Vps4 disassembly machinery and the accessory ESCRT-III proteins. This provides an additional level of regulation and coordination for ESCRT-III assembly and disassembly.« less

Understanding brassinosteroid-regulated mechanisms to improve stress tolerance in plants: a critical review.

PubMed

Nawaz, Fahim; Naeem, Muhammad; Zulfiqar, Bilal; Akram, Asim; Ashraf, Muhammad Yasin; Raheel, Muhammad; Shabbir, Rana Nauman; Hussain, Rai Altaf; Anwar, Irfan; Aurangzaib, Muhammad

2017-07-01

Brassinosteroids (BRs) are steroidal plant hormones involved in regulation of physiological and molecular processes to ameliorate various biotic and abiotic stresses. Exogenous application of BRs to improve stress tolerance in plants has recently become a high research priority. Several studies have revealed the involvement of these steroidal hormones in upregulation of stress-related defense genes and their cross talk with other metabolic pathways. This is likely to stimulate research on many unanswered questions regarding their role in enhancing the ability of plants to tolerate adverse environmental conditions. Thus, this review appraises new insights on mechanisms mediating BR-regulated changes in plants, focused mainly on their involvement in regulation of physiological and molecular mechanisms under stress conditions. Herein, examples of BR-stimulated modulation of antioxidant defense system and upregulation of transcription factors in plants exposed to various biotic (bacterial, viral, and fungal attack) and abiotic stresses (drought, salinity, heat, low temperature, and heavy metal stress) are discussed. Based on these insights, future research in the current direction can be helpful to increase our understanding of BR-mediated complex and interrelated processes under stress conditions.

Structural basis of Vta1 function in the multi-vesicular body sorting pathway

PubMed Central

Xiao, Junyu; Xia, Hengchuan; Zhou, Jiahai; Azmi, Ishara; Davies, Brian A.; Katzmann, David J.; Xu, Zhaohui

2009-01-01

Summary The MVB pathway plays essential roles in several eukaryotic cellular processes. Proper function of the MVB pathway requires reversible membrane association of the ESCRTs, a process catalyzed by Vps4 ATPase. Vta1 regulates the Vps4 activity but its mechanism of action was poorly understood. We report the high-resolution crystal structures of the Did2- and Vps60-binding N-terminal domain and the Vps4-binding C-terminal domain of S. cerevisiae Vta1. The C-terminal domain also mediates Vta1 dimerization and both subunits are required for its function as a Vps4 regulator. Emerging from our analysis is a mechanism of regulation by Vta1 in which the C-terminal domain stabilizes the ATP-dependent double ring assembly of Vps4. In addition, the MIT motif containing N-terminal domain, projected by a long disordered linker, allows contact between the Vps4 disassembly machinery and the accessory ESCRT-III proteins. This provides an additional level of regulation and coordination for ESCRT-III assembly and disassembly. PMID:18194651

Combined effects of hydrologic alteration and cyprinid fish in mediating biogeochemical processes in a Mediterranean stream.

PubMed

Rubio-Gracia, Francesc; Almeida, David; Bonet, Berta; Casals, Frederic; Espinosa, Carmen; Flecker, Alexander S; García-Berthou, Emili; Martí, Eugènia; Tuulaikhuu, Baigal-Amar; Vila-Gispert, Anna; Zamora, Lluis; Guasch, Helena

2017-12-01

Flow regimes are important drivers of both stream community and biogeochemical processes. However, the interplay between community and biogeochemical responses under different flow regimes in streams is less understood. In this study, we investigated the structural and functional responses of periphyton and macroinvertebrates to different densities of the Mediterranean barbel (Barbus meridionalis, Cyprinidae) in two stream reaches differing in flow regime. The study was conducted in Llémena Stream, a small calcareous Mediterranean stream with high nutrient levels. We selected a reach with permanent flow (permanent reach) and another subjected to flow regulation (regulated reach) with periods of flow intermittency. At each reach, we used in situ cages to generate 3 levels of fish density. Cages with 10 barbels were used to simulate high fish density (>7indm -2 ); cages with open sides were used as controls (i.e. exposed to actual fish densities of each stream reach) thus having low fish density; and those with no fish were used to simulate the disappearance of fish that occurs with stream drying. Differences in fish density did not cause significant changes in periphyton biomass and macroinvertebrate density. However, phosphate uptake by periphyton was enhanced in treatments lacking fish in the regulated reach with intermittent flow but not in the permanent reach, suggesting that hydrologic alteration hampers the ability of biotic communities to compensate for the absence of fish. This study indicates that fish density can mediate the effects of anthropogenic alterations such as flow intermittence derived from hydrologic regulation on stream benthic communities and associated biogeochemical processes, at least in eutrophic streams. Copyright © 2017. Published by Elsevier B.V.

Evaluation of ecological instream flow using multiple ecological indicators with consideration of hydrological alterations

NASA Astrophysics Data System (ADS)

Zhang, Qiang; Gu, Xihui; Singh, Vijay P.; Chen, Xiaohong

2015-10-01

Dam-induced hydrological alterations and related ecological problems have been arousing considerable concern from hydrologists, ecologists, and policy-makers. The East River basin in China is the major provider of water resources for mega-cities within the Pearl River Delta and meets 80% of annual water demand of Hong Kong. In this study, ecodeficit and ecosurplus were analyzed to determine the ecological impact of water impoundments. Also, Do and DHRAM were employed to evaluate the degree of alteration of hydrological regimes, and ERHIs were analyzed to evaluate the influence of hydrological alterations on ecological diversity. Results indicate that: (1) the magnitude and frequency of high flows decrease and those of low flows increase due to the regulation of reservoirs; (2) variations of annual ecosurplus are mainly the result of precipitation changes and the annual ecodeficit is significantly influenced by reservoirs. However, ecodeficit and ecosurplus in other seasons, particularly autumn and winter, are more influenced by reservoir regulation; (3) impacts of reservoirs on hydrological regimes and eco-flow regimes are different from one station to another due to different degrees of influence of reservoirs on hydrological processes at different stations. The longer the distance between a reservoir and a hydrological station is, the weaker the influence the water reservoir has on the hydrological processes; (4) ecodeficit and ecosurplus can be accepted in the evaluation of alterations of hydrological processes at annual and seasonal time scales. Results of Shannon Index indicate decreasing biological diversity after the construction of water reservoirs, implying negative impacts of water reservoirs on biological diversity of a river basin and this should arouse considerable human concerns. This study provides a theoretical background for water resources management with consideration of eco-flow variations due to reservoir regulation in other highly-regulated river basins of the globe.

Quantitative Proteomic Profiling of Low Dose Ionizing Radiation Effects in a Human Skin Model

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

Hengel, Shawna; Aldrich, Joshua T.; Waters, Katrina M.

2014-07-29

To assess molecular responses to low doses of radiation that may be encountered during medical diagnostic procedures, nuclear accidents, or terrorist acts, a quantitative global proteomic approach was used to identify protein alterations in a reconstituted human skin tissue treated with 10 cGy of ionizing radiation. Subcellular fractionation was employed to remove highly abundant structural proteins and provide insight on radiation induced alterations in protein abundance and localization. In addition, peptides were post-fractionated using high resolution 2-dimensional liquid chromatography to increase the dynamic range of detection of protein abundance and translocation changes. Quantitative data was obtained by labeling peptides withmore » 8-plex isobaric iTRAQ tags. A total of 207 proteins were detected with statistically significant alterations in abundance and/or subcellular localization compared to sham irradiated tissues. Bioinformatics analysis of the data indicated that the top canonical pathways affected by low dose radiation are related to cellular metabolism. Among the proteins showing alterations in abundance, localization and proteolytic processing was the skin barrier protein filaggrin which is consistent with our previous observation that ionizing radiation alters profilaggrin processing with potential effects on skin barrier functions. In addition, a large number of proteases and protease regulators were affected by low dose radiation exposure indicating that altered proteolytic activity may be a hallmark of low dose radiation exposure. While several studies have demonstrated altered transcriptional regulation occurs following low dose radiation exposures, the data presented here indicates post-transcriptional regulation of protein abundance, localization, and proteolytic processing play an important role in regulating radiation responses in complex human tissues.« less

Thymoquinone-rich fraction nanoemulsion (TQRFNE) decreases Aβ40 and Aβ42 levels by modulating APP processing, up-regulating IDE and LRP1, and down-regulating BACE1 and RAGE in response to high fat/cholesterol diet-induced rats.

PubMed

Ismail, Norsharina; Ismail, Maznah; Azmi, Nur Hanisah; Bakar, Muhammad Firdaus Abu; Yida, Zhang; Abdullah, Maizaton Atmadini; Basri, Hamidon

2017-11-01

Though the causes of Alzheimer's disease (AD) are yet to be understood, much evidence has suggested that excessive amyloid-β (Aβ) accumulation due to abnormal amyloid-β precursor protein (APP) processing and Aβ metabolism are crucial processes towards AD pathogenesis. Hence, approaches aiming at APP processing and Aβ metabolism are currently being actively pursued for the management of AD. Studies suggest that high cholesterol and a high fat diet have harmful effects on cognitive function and may instigate the commencement of AD pathogenesis. Despite the neuropharmacological attributes of black cumin seed (Nigella sativa) extracts and its main active compound, thymoquinone (TQ), limited records are available in relation to AD research. Nanoemulsion (NE) is exploited as drug delivery systems due to their capacity of solubilising non-polar active compounds and is widely examined for brain targeting. Herewith, the effects of thymoquinone-rich fraction nanoemulsion (TQRFNE), thymoquinone nanoemulsion (TQNE) and their counterparts' conventional emulsion in response to high fat/cholesterol diet (HFCD)-induced rats were investigated. Particularly, the Aβ generation; APP processing, β-secretase 1 (BACE1), γ-secretases of presenilin 1 (PSEN1) and presenilin 2 (PSEN2), Aβ degradation; insulin degrading enzyme (IDE), Aβ transportation; low density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) were measured in brain tissues. TQRFNE reduced the brain Aβ fragment length 1-40 and 1-42 (Aβ40 and Aβ42) levels, which would attenuate the AD pathogenesis. This reduction could be due to the modulation of β- and γ-secretase enzyme activity, and the Aβ degradation and transportation in/out of the brain. The findings show the mechanistic actions of TQRFNE in response to high fat and high cholesterol diet associated to Aβ generation, degradation and transportation in the rat's brain tissue. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Safety Sufficiency for NextGen: Assessment of Selected Existing Safety Methods, Tools, Processes, and Regulations

NASA Technical Reports Server (NTRS)

Xu, Xidong; Ulrey, Mike L.; Brown, John A.; Mast, James; Lapis, Mary B.

2013-01-01

NextGen is a complex socio-technical system and, in many ways, it is expected to be more complex than the current system. It is vital to assess the safety impact of the NextGen elements (technologies, systems, and procedures) in a rigorous and systematic way and to ensure that they do not compromise safety. In this study, the NextGen elements in the form of Operational Improvements (OIs), Enablers, Research Activities, Development Activities, and Policy Issues were identified. The overall hazard situation in NextGen was outlined; a high-level hazard analysis was conducted with respect to multiple elements in a representative NextGen OI known as OI-0349 (Automation Support for Separation Management); and the hazards resulting from the highly dynamic complexity involved in an OI-0349 scenario were illustrated. A selected but representative set of the existing safety methods, tools, processes, and regulations was then reviewed and analyzed regarding whether they are sufficient to assess safety in the elements of that OI and ensure that safety will not be compromised and whether they might incur intolerably high costs.

Biofilm formation and sanitizer resistance contributes to “High Event” meat contamination by E. coli O157:H7

USDA-ARS?s Scientific Manuscript database

Background E. coli O157:H7 is an important foodborne pathogen responsible for numerous outbreaks worldwide. FSIS regulates this pathogen as an adulterant in meat products, and a “High Event Period” is defined as a time period in which commercial meat processing plants experience a higher than usual ...

Myb-binding protein 1a (Mybbp1a) regulates levels and processing of pre-ribosomal RNA.

PubMed

Hochstatter, Julia; Hölzel, Michael; Rohrmoser, Michaela; Schermelleh, Lothar; Leonhardt, Heinrich; Keough, Rebecca; Gonda, Thomas J; Imhof, Axel; Eick, Dirk; Längst, Gernot; Németh, Attila

2012-07-13

Ribosomal RNA gene transcription, co-transcriptional processing, and ribosome biogenesis are highly coordinated processes that are tightly regulated during cell growth. In this study we discovered that Mybbp1a is associated with both the RNA polymerase I complex and the ribosome biogenesis machinery. Using a reporter assay that uncouples transcription and RNA processing, we show that Mybbp1a represses rRNA gene transcription. In addition, overexpression of the protein reduces RNA polymerase I loading on endogenous rRNA genes as revealed by chromatin immunoprecipitation experiments. Accordingly, depletion of Mybbp1a results in an accumulation of the rRNA precursor in vivo but surprisingly also causes growth arrest of the cells. This effect can be explained by the observation that the modulation of Mybbp1a protein levels results in defects in pre-rRNA processing within the cell. Therefore, the protein may play a dual role in the rRNA metabolism, potentially linking and coordinating ribosomal DNA transcription and pre-rRNA processing to allow for the efficient synthesis of ribosomes.

Measuring Helicase Inhibition of the DEAD-box Protein Dbp2 by Yra1

PubMed Central

Ma, Wai Kit; Tran, Elizabeth J.

2016-01-01

Despite the highly conserved helicase core, individual DEAD-box proteins are specialized in diverse RNA metabolic processes. One mechanism that determines DEAD-box protein specificity is enzymatic regulation by other protein cofactors. In this chapter, we describe a protocol for purifying the Saccharomyces cerevisiae DEAD-box RNA helicase Dbp2 and RNA-binding protein Yra1 and subsequent analysis of helicase regulation. The experiments described here can be adapted to RNA helicase and purified co-factor. PMID:25579587

Plants with modified lignin content and methods for production thereof

DOEpatents

Zhao, Qiao; Chen, Fang; Dixon, Richard A.

2014-08-05

The invention provides methods for decreasing lignin content and for increasing the level of fermentable carbohydrates in plants by down-regulation of the NST transcription factor. Nucleic acid constructs for down-regulation of NST are described. Transgenic plants are provided that comprise reduced lignin content. Plants described herein may be used, for example, as improved biofuel feedstock and as highly digestible forage crops. Methods for processing plant tissue and for producing ethanol by utilizing such plants are also provided.

Identification of new developmentally regulated genes involved in Streptomyces coelicolor sporulation.

PubMed

Salerno, Paola; Persson, Jessica; Bucca, Giselda; Laing, Emma; Ausmees, Nora; Smith, Colin P; Flärdh, Klas

2013-12-05

The sporulation of aerial hyphae of Streptomyces coelicolor is a complex developmental process. Only a limited number of the genes involved in this intriguing morphological differentiation programme are known, including some key regulatory genes. The aim of this study was to expand our knowledge of the gene repertoire involved in S. coelicolor sporulation. We report a DNA microarray-based investigation of developmentally controlled gene expression in S. coelicolor. By comparing global transcription patterns of the wild-type parent and two mutants lacking key regulators of aerial hyphal sporulation, we found a total of 114 genes that had significantly different expression in at least one of the two mutants compared to the wild-type during sporulation. A whiA mutant showed the largest effects on gene expression, while only a few genes were specifically affected by whiH mutation. Seven new sporulation loci were investigated in more detail with respect to expression patterns and mutant phenotypes. These included SCO7449-7451 that affect spore pigment biogenesis; SCO1773-1774 that encode an L-alanine dehydrogenase and a regulator-like protein and are required for maturation of spores; SCO3857 that encodes a protein highly similar to a nosiheptide resistance regulator and affects spore maturation; and four additional loci (SCO4421, SCO4157, SCO0934, SCO1195) that show developmental regulation but no overt mutant phenotype. Furthermore, we describe a new promoter-probe vector that takes advantage of the red fluorescent protein mCherry as a reporter of cell type-specific promoter activity. Aerial hyphal sporulation in S. coelicolor is a technically challenging process for global transcriptomic investigations since it occurs only as a small fraction of the colony biomass and is not highly synchronized. Here we show that by comparing a wild-type to mutants lacking regulators that are specifically affecting processes in aerial hypha, it is possible to identify previously unknown genes with important roles in sporulation. The transcriptomic data reported here should also serve as a basis for identification of further developmentally important genes in future functional studies.

Methods to study maternal regulation of germ cell specification in zebrafish

PubMed Central

Kaufman, O.H.; Marlow, F.L.

2016-01-01

The process by which the germ line is specified in the zebrafish embryo is under the control of maternal gene products that were produced during oogenesis. Zebrafish are highly amenable to microscopic observation of the processes governing maternal germ cell specification because early embryos are transparent, and the germ line is specified rapidly (within 4–5 h post fertilization). Advantages of zebrafish over other models used to study vertebrate germ cell formation include their genetic tractability, the large numbers of progeny, and the easily manipulable genome, all of which make zebrafish an ideal system for studying the genetic regulators and cellular basis of germ cell formation and maintenance. Classical molecular biology techniques, including expression analysis through in situ hybridization and forward genetic screens, have laid the foundation for our understanding of germ cell development in zebrafish. In this chapter, we discuss some of these classic techniques, as well as recent cutting-edge methodologies that have improved our ability to visualize the process of germ cell specification and differentiation, and the tracking of specific molecules involved in these processes. Additionally, we discuss traditional and novel technologies for manipulating the zebrafish genome to identify new components through loss-of-function studies of putative germ cell regulators. Together with the numerous aforementioned advantages of zebrafish as a genetic model for studying development, we believe these new techniques will continue to advance zebrafish to the forefront for investigation of the molecular regulators of germ cell specification and germ line biology. PMID:27312489

Systematic Genetic Screen for Transcriptional Regulators of the Candida albicans White-Opaque Switch.

PubMed

Lohse, Matthew B; Ene, Iuliana V; Craik, Veronica B; Hernday, Aaron D; Mancera, Eugenio; Morschhäuser, Joachim; Bennett, Richard J; Johnson, Alexander D

2016-08-01

The human fungal pathogen Candida albicans can reversibly switch between two cell types named "white" and "opaque," each of which is stable through many cell divisions. These two cell types differ in their ability to mate, their metabolic preferences and their interactions with the mammalian innate immune system. A highly interconnected network of eight transcriptional regulators has been shown to control switching between these two cell types. To identify additional regulators of the switch, we systematically and quantitatively measured white-opaque switching rates of 196 strains, each deleted for a specific transcriptional regulator. We identified 19 new regulators with at least a 10-fold effect on switching rates and an additional 14 new regulators with more subtle effects. To investigate how these regulators affect switching rates, we examined several criteria, including the binding of the eight known regulators of switching to the control region of each new regulatory gene, differential expression of the newly found genes between cell types, and the growth rate of each mutant strain. This study highlights the complexity of the transcriptional network that regulates the white-opaque switch and the extent to which switching is linked to a variety of metabolic processes, including respiration and carbon utilization. In addition to revealing specific insights, the information reported here provides a foundation to understand the highly complex coupling of white-opaque switching to cellular physiology. Copyright © 2016 by the Genetics Society of America.

Clock genes and their genomic distributions in three species of salmonid fishes: Associations with genes regulating sexual maturation and cell cycling

PubMed Central

2010-01-01

Background Clock family genes encode transcription factors that regulate clock-controlled genes and thus regulate many physiological mechanisms/processes in a circadian fashion. Clock1 duplicates and copies of Clock3 and NPAS2-like genes were partially characterized (genomic sequencing) and mapped using family-based indels/SNPs in rainbow trout (RT)(Oncorhynchus mykiss), Arctic charr (AC)(Salvelinus alpinus), and Atlantic salmon (AS)(Salmo salar) mapping panels. Results Clock1 duplicates mapped to linkage groups RT-8/-24, AC-16/-13 and AS-2/-18. Clock3/NPAS2-like genes mapped to RT-9/-20, AC-20/-43, and AS-5. Most of these linkage group regions containing the Clock gene duplicates were derived from the most recent 4R whole genome duplication event specific to the salmonids. These linkage groups contain quantitative trait loci (QTL) for life history and growth traits (i.e., reproduction and cell cycling). Comparative synteny analyses with other model teleost species reveal a high degree of conservation for genes in these chromosomal regions suggesting that functionally related or co-regulated genes are clustered in syntenic blocks. For example, anti-müllerian hormone (amh), regulating sexual maturation, and ornithine decarboxylase antizymes (oaz1 and oaz2), regulating cell cycling, are contained within these syntenic blocks. Conclusions Synteny analyses indicate that regions homologous to major life-history QTL regions in salmonids contain many candidate genes that are likely to influence reproduction and cell cycling. The order of these genes is highly conserved across the vertebrate species examined, and as such, these genes may make up a functional cluster of genes that are likely co-regulated. CLOCK, as a transcription factor, is found within this block and therefore has the potential to cis-regulate the processes influenced by these genes. Additionally, clock-controlled genes (CCGs) are located in other life-history QTL regions within salmonids suggesting that at least in part, trans-regulation of these QTL regions may also occur via Clock expression. PMID:20670436

Pharmaceuticals and Wastewater Tracers Along the Lower Hudson River

EPA Science Inventory

The behavior and fate of pharmaceutical residues in urbanized, coastal ecosystems is not well understood. In this study 16 highly prescribed pharmaceuticals were measured in the lower Hudson River and New York Harbor in order to elucidate factors and processes regulating their ...

Transcriptomic Analysis Implies That GA Regulates Sex Expression via Ethylene-Dependent and Ethylene-Independent Pathways in Cucumber (Cucumis sativus L.).

PubMed

Zhang, Yan; Zhao, Guiye; Li, Yushun; Mo, Ning; Zhang, Jie; Liang, Yan

2017-01-01

Sex differentiation of flower buds is an important developmental process that directly affects fruit yield of cucumber ( Cucumis sativus L.). Plant hormones, such as gibberellins (GAs) and ethylene can promote development of male and female flowers, respectively, however, the regulatory mechanisms of GA-induced male flower formation and potential involvement of ethylene in this process still remain unknown. In this study, to unravel the genes and gene networks involved in GA-regulated cucumber sexual development, we performed high throughout RNA-Seq analyses that compared the transcriptomes of shoot tips between GA 3 treated and untreated gynoecious cucumber plants. Results showed that GA 3 application markedly induced male flowers but decreased ethylene production in shoot tips. Furthermore, the transcript levels of M ( CsACS2 ) gene, ethylene receptor CsETR1 and some ethylene-responsive transcription factors were dramatically changed after GA 3 treatment, suggesting a potential involvement of ethylene in GA-regulated sex expression of cucumber. Interestingly, GA 3 down-regulated transcript of a C-class floral homeotic gene, CAG2 , indicating that GA may also influence cucumber sex determination through an ethylene-independent process. These results suggest a novel model for hormone-mediated sex differentiation and provide a theoretical basis for further dissection of the regulatory mechanism of male flower formation in cucumber. Statement: We reveal that GA can regulate sex expression of cucumber via an ethylene-dependent manner, and the M ( CsACS2 ), CsETR1 , and ERFs are probably involved in this process. Moreover, CAG2 , a C-class floral homeotic gene, may also participate in GA-modulated cucumber sex determination, but this pathway is ethylene-independent.

Structural Requirement in Clostridium perfringens Collagenase mRNA 5′ Leader Sequence for Translational Induction through Small RNA-mRNA Base Pairing

PubMed Central

Nomura, Nobuhiko; Nakamura, Kouji

2013-01-01

The Gram-positive anaerobic bacterium Clostridium perfringens is pathogenic to humans and animals, and the production of its toxins is strictly regulated during the exponential phase. We recently found that the 5′ leader sequence of the colA transcript encoding collagenase, which is a major toxin of this organism, is processed and stabilized in the presence of the small RNA VR-RNA. The primary colA 5′-untranslated region (5′UTR) forms a long stem-loop structure containing an internal bulge and masks its own ribosomal binding site. Here we found that VR-RNA directly regulates colA expression through base pairing with colA mRNA in vivo. However, when the internal bulge structure was closed by point mutations in colA mRNA, translation ceased despite the presence of VR-RNA. In addition, a mutation disrupting the colA stem-loop structure induced mRNA processing and ColA-FLAG translational activation in the absence of VR-RNA, indicating that the stem-loop and internal bulge structure of the colA 5′ leader sequence is important for regulation by VR-RNA. On the other hand, processing was required for maximal ColA expression but was not essential for VR-RNA-dependent colA regulation. Finally, colA processing and translational activation were induced at a high temperature without VR-RNA. These results suggest that inhibition of the colA 5′ leader structure through base pairing is the primary role of VR-RNA in colA regulation and that the colA 5′ leader structure is a possible thermosensor. PMID:23585542

Transcriptomic Responses to Salinity Stress in the Pacific Oyster Crassostrea gigas

PubMed Central

Zhao, Xuelin; Yu, Hong; Kong, Lingfeng; Li, Qi

2012-01-01

Background Low salinity is one of the main factors limiting the distribution and survival of marine species. As a euryhaline species, the Pacific oyster Crassostrea gigas is considered to be tolerant to relative low salinity. The genes that regulate C. gigas responses to osmotic stress were monitored using the next-generation sequencing of whole transcriptome with samples taken from gills. By RNAseq technology, transcript catalogs of up- and down-regulated genes were generated from the oysters exposed to low and optimal salinity seawater. Methodology/Principal Findings Through Illumina sequencing, we reported 1665 up-regulated transcripts and 1815 down-regulated transcripts. A total of 45771 protein-coding contigs were identified from two groups based on sequence similarities with known proteins. As determined by GO annotation and KEGG pathway mapping, functional annotation of the genes recovered diverse biological functions and processes. The genes that changed expression significantly were highly represented in cellular process and regulation of biological process, intracellular and cell, binding and protein binding according to GO annotation. The results highlighted genes related to osmoregulation, signaling and interactions of osmotic stress response, anti-apoptotic reactions as well as immune response, cell adhesion and communication, cytoskeleton and cell cycle. Conclusions/Significance Through more than 1.5 million sequence reads and the expression data of the two libraries, the study provided some useful insights into signal transduction pathways in oysters and offered a number of candidate genes as potential markers of tolerance to hypoosmotic stress for oysters. In addition, the characterization of C. gigas transcriptome will not only provide a better understanding of the molecular mechanisms about the response to osmotic stress of the oysters, but also facilitate research into biological processes to find underlying physiological adaptations to hypoosmotic shock for marine invertebrates. PMID:23029449

Proteomic Analysis Reveals the Positive Effect of Exogenous Spermidine in Tomato Seedlings' Response to High-Temperature Stress

PubMed Central

Sang, Qinqin; Shan, Xi; An, Yahong; Shu, Sheng; Sun, Jin; Guo, Shirong

2017-01-01

Polyamines are phytohormones that regulate plant growth and development as well as the response to environmental stresses. To evaluate their functions in high-temperature stress responses, the effects of exogenous spermidine (Spd) were determined in tomato leaves using two-dimensional electrophoresis and MALDI-TOF/TOF MS. A total of 67 differentially expressed proteins were identified in response to high-temperature stress and/or exogenous Spd, which were grouped into different categories according to biological processes. The four largest categories included proteins involved in photosynthesis (27%), cell rescue, and defense (24%), protein synthesis, folding and degradation (22%), and energy and metabolism (13%). Exogenous Spd up-regulated most identified proteins involved in photosynthesis, implying an enhancement in photosynthetic capacity. Meanwhile, physiological analysis showed that Spd could improve net photosynthetic rate and the biomass accumulation. Moreover, an increased high-temperature stress tolerance by exogenous Spd would contribute to the higher expressions of proteins involved in cell rescue and defense, and Spd regulated the antioxidant enzymes activities and related genes expression in tomato seedlings exposed to high temperature. Taken together, these findings provide a better understanding of the Spd-induced high-temperature resistance by proteomic approaches, providing valuable insight into improving the high-temperature stress tolerance in the global warming epoch. PMID:28220137

Proteomic Analysis Reveals the Positive Effect of Exogenous Spermidine in Tomato Seedlings' Response to High-Temperature Stress.

PubMed

Sang, Qinqin; Shan, Xi; An, Yahong; Shu, Sheng; Sun, Jin; Guo, Shirong

2017-01-01

Polyamines are phytohormones that regulate plant growth and development as well as the response to environmental stresses. To evaluate their functions in high-temperature stress responses, the effects of exogenous spermidine (Spd) were determined in tomato leaves using two-dimensional electrophoresis and MALDI-TOF/TOF MS. A total of 67 differentially expressed proteins were identified in response to high-temperature stress and/or exogenous Spd, which were grouped into different categories according to biological processes. The four largest categories included proteins involved in photosynthesis (27%), cell rescue, and defense (24%), protein synthesis, folding and degradation (22%), and energy and metabolism (13%). Exogenous Spd up-regulated most identified proteins involved in photosynthesis, implying an enhancement in photosynthetic capacity. Meanwhile, physiological analysis showed that Spd could improve net photosynthetic rate and the biomass accumulation. Moreover, an increased high-temperature stress tolerance by exogenous Spd would contribute to the higher expressions of proteins involved in cell rescue and defense, and Spd regulated the antioxidant enzymes activities and related genes expression in tomato seedlings exposed to high temperature. Taken together, these findings provide a better understanding of the Spd-induced high-temperature resistance by proteomic approaches, providing valuable insight into improving the high-temperature stress tolerance in the global warming epoch.

Social Regulation of Learning During Collaborative Inquiry Learning in Science: How does it emerge and what are its functions?

NASA Astrophysics Data System (ADS)

Ucan, Serkan; Webb, Mary

2015-10-01

Students' ability to regulate their learning is considered important for the quality of collaborative inquiry learning. However, there is still limited understanding about how students engage in social forms of regulation processes and what roles these regulatory processes may play during collaborative learning. The purpose of this study was to identify when and how co- and shared regulation of metacognitive, emotional and motivational processes emerge and function during collaborative inquiry learning in science. Two groups of three students (aged 12) from a private primary school in Turkey were videotaped during collaborative inquiry activities in a naturalistic classroom setting over a seven-week period, and the transcripts were analysed in order to identify their use of regulation processes. Moreover, this was combined with the analysis of stimulated-recall interviews with the student groups. Results indicated that co- and shared regulation processes were often initiated by particular events and played a crucial role in the success of students' collaborative inquiry learning. Co-regulation of metacognitive processes had the function of stimulating students to reflect upon and clarify their thinking, as well as facilitating the construction of new scientific understanding. Shared regulation of metacognitive processes helped students to build a shared understanding of the task, clarify and justify their shared perspective, and sustain the ongoing knowledge co-construction. Moreover, the use of shared emotional and motivational regulation was identified as important for sustaining reciprocal interactions and creating a positive socio-emotional atmosphere within the groups. In addition, the findings revealed links between the positive quality of group interactions and the emergence of co- and shared regulation of metacognitive processes. This study highlights the importance of fostering students' acquisition and use of regulation processes during collaborative inquiry learning.

In-situ Substrate Addition to Create Reactive Zones for Treatment of Chlorinated Aliphatic Hydrocarbons: Hanscom Air Force Base

DTIC Science & Technology

2003-04-04

processes in the subsurface. This substrate is typically molasses although these substrates can include high fructose corn syrup , whey, etc. (Suthersan...typically comprised of a carbohydrate such as molasses, whey, high fructose corn syrup , lactate, butyrate, or benzoate). Through periodic subsurface...this purpose; other carbohydrates such as high fructose corn syrup and whey can also be effective. This approach has been accepted by regulators and

High-order sliding-mode control for blood glucose regulation in the presence of uncertain dynamics.

PubMed

Hernández, Ana Gabriela Gallardo; Fridman, Leonid; Leder, Ron; Andrade, Sergio Islas; Monsalve, Cristina Revilla; Shtessel, Yuri; Levant, Arie

2011-01-01

The success of blood glucose automatic regulation depends on the robustness of the control algorithm used. It is a difficult task to perform due to the complexity of the glucose-insulin regulation system. The variety of model existing reflects the great amount of phenomena involved in the process, and the inter-patient variability of the parameters represent another challenge. In this research a High-Order Sliding-Mode Control is proposed. It is applied to two well known models, Bergman Minimal Model, and Sorensen Model, to test its robustness with respect to uncertain dynamics, and patients' parameter variability. The controller designed based on the simulations is tested with the specific Bergman Minimal Model of a diabetic patient whose parameters were identified from an in vivo assay. To minimize the insulin infusion rate, and avoid the hypoglycemia risk, the glucose target is a dynamical profile.

Cortical activation deficits during facial emotion processing in youth at high risk for the development of substance use disorders.

PubMed

Hulvershorn, Leslie A; Finn, Peter; Hummer, Tom A; Leibenluft, Ellen; Ball, Brandon; Gichina, Victoria; Anand, Amit

2013-08-01

Recent longitudinal studies demonstrate that addiction risk may be influenced by a cognitive, affective and behavioral phenotype that emerges during childhood. Relatively little research has focused on the affective or emotional risk components of this high-risk phenotype, including the relevant neurobiology. Non-substance abusing youth (N=19; mean age=12.2) with externalizing psychopathology and paternal history of a substance use disorder and demographically matched healthy comparisons (N=18; mean age=11.9) were tested on a facial emotion matching task during functional MRI. This task involved matching faces by emotions (angry, anxious) or matching shape orientation. High-risk youth exhibited increased medial prefrontal, precuneus and occipital cortex activation compared to the healthy comparison group during the face matching condition, relative to the control shape condition. The occipital activation correlated positively with parent-rated emotion regulation impairments in the high-risk group. These findings suggest a preexisting abnormality in cortical activation in response to facial emotion matching in youth at high risk for the development of problem drug or alcohol use. These cortical deficits may underlie impaired affective processing and regulation, which in turn may contribute to escalating drug use in adolescence. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Cortical Activation Deficits During Facial Emotion Processing in Youth at High Risk for the Development of Substance Use Disorders*

PubMed Central

Hulvershorn, Leslie A.; Finn, Peter; Hummer, Tom A.; Leibenluft, Ellen; Ball, Brandon; Gichina, Victoria; Anand, Amit

2013-01-01

Background Recent longitudinal studies demonstrate that addiction risk may be influenced by a cognitive, affective and behavioral phenotype that emerges during childhood. Relatively little research has focused on the affective or emotional risk components of this high-risk phenotype, including the relevant neurobiology. Methods Non-substance abusing youth (N = 19; mean age = 12.2) with externalizing psychopathology and paternal history of a substance use disorder and demographically matched healthy comparisons (N=18; mean age = 11.9) were tested on a facial emotion matching task during functional MRI. This task involved matching faces by emotions (angry, anxious) or matching shape orientation. Results High-risk youth exhibited increased medial prefrontal, precuneus and occipital cortex activation compared to the healthy comparison group during the face matching condition, relative to the control shape condition. The occipital activation correlated positively with parent-rated emotion regulation impairments in the high-risk group. Conclusions These findings suggest a preexisting abnormality in cortical activation in response to facial emotion matching in youth at high risk for the development of problem drug or alcohol use. These cortical deficits may underlie impaired affective processing and regulation, which in turn may contribute to escalating drug use in adolescence. PMID:23768841

NOx control techniques for the CPI

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

Lambert, D.; McGowan, T.F.

1996-06-01

After years of air pollution control innovation, the control of emissions of nitrogen oxide compounds stands out as an area where much work remains to be performed in the chemical process industries (CPI). Federal regulations, ozone non-attainment areas, acid rain provisions of the US Clean Air Act, and corporate goals for emission reductions are all motivators. Primary CPI sources are high-temperature combustion systems, including fired heaters, boilers and Kilns. Nitrogen-based processes such as nitric acid manufacture also contribute. The paper discusses the regulations which define the problem and some solutions. These include fuel switching, low-excess air burners, fluegas recirculation, stagedmore » combustion, out of service burners, and wet scrubbing of flue gas. The paper briefly discusses costs of these options.« less

How are drugs approved? Part 1: the evolution of the Food and Drug Administration.

PubMed

Howland, Robert H

2008-01-01

The discovery, development, and marketing of drugs for clinical use is a process that is complex, arduous, expensive, highly regulated, often criticized, and sometimes controversial. In the United States, the Food and Drug Administration (FDA) is the governmental agency responsible for regulating the development and marketing of drugs, medical devices, biologics, foods, cosmetics, radiation-emitting electronic devices, and veterinary products, with the objective of ensuring their safety and efficacy. As part of a broad overview of the drug development process, this article will describe the historical evolution of the FDA. This will provide background for two subsequent articles in this series, which will describe the ethical foundations of clinical research and hethe stages of drug development.

Population-regulating processes during the adult phase in flatfish

NASA Astrophysics Data System (ADS)

Rijnsdorp, A. D.

Flatfish support major fisheries and the study of regulatory processes are of paramount importance for evaluating the resilience of the resource to exploitation. This paper reviews the evidence for processes operating during the adult phase that may 1. generate interannual variability in recruitment; 2. contribute to population regulation through density-dependent growth, density-dependent ripening of adults and density-dependent egg production. With regard to (1), there is evidence that in the adult phase processes do occur that may generate recruitment variability through variation in size-specific fecundity, contraction of spawning season, reduction in egg quality, change in sex ratio and size composition of the adult population. However, time series of recruitment do not provide support for this hypothesis. With regard to (2), there is ample evidence that exploitation of flatfish coincides with an increase in growth, although the mechanisms involved are not always clear. The presence of density-dependent growth in the adult phase of unexploited populations appears to be the most likely explanation in some cases. From the early years of exploitation of flatfish stocks inhabiting cold waters, evidence exists that adult fish do not spawn each year. Fecundity schedules show annual variations, but the available information suggests that size-specific fecundity is stable over a broad range of population abundance and may only decrease at high population abundance. The analysis is complicated by the possibility of a trade-off between egg numbers and egg size. Nevertheless, a density-dependent decrease in growth will automatically result in a decrease in absolute fecundity because of the reduced body size. The potential contribution of these regulatory effects on population regulation is explored. Results indicate that density-dependent ripening and absolute fecundity, mediated through density-dependent growth, may control recruitment at high levels of population abundance. The effect of a density-dependent decrease in size-specific fecundity seems to play a minor role, although this role may become important at extremely high levels of population abundance.

[Coactivators in energy metabolism: peroxisome proliferator-activated receptor-gamma coactivator 1 family].

PubMed

Wang, Rui; Chang, Yong-sheng; Fang, Fu-de

2009-12-01

Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) family is highly expressed in tissues with high energy metabolism. They coactivate transcription factors in regulating genes engaged in processes such as gluconeogenesis, adipose beta-oxydation, lipoprotein synthesis and secretion, mitochondrial biogenesis, and oxidative metabolism. Protein conformation studies demonstrated that they lack DNA binding domains and act as coactivators through physical interaction with transcription factors. PGC1 activity is regulated at transcription level or by multiple covalent chemical modifications such as phosphorylation, methylation and acetylation/deacetylation. Abnormal expression of PGC1 coactivators usually is closely correlated with diseases such as diabetes, obesity, hyperglycemia, hyperlipemia, and arterial and brain neuron necrosis diseases.

Diurnal dynamics of oxygen and carbon dioxide concentrations in shoots and rhizomes of a perennial in a constructed wetland indicate down-regulation of below ground oxygen consumption

PubMed Central

Faußer, Anna C.; Dušek, Jiří; Čížková, Hana; Kazda, Marian

2016-01-01

Wetland plants actively provide oxygen for aerobic processes in submerged tissues and the rhizosphere. The novel concomitant assessment of diurnal dynamics of oxygen and carbon dioxide concentrations under field conditions tests the whole-system interactions in plant-internal gas exchange and regulation. Oxygen concentrations ([O2]) were monitored in-situ in central culm and rhizome pith cavities of common reed (Phragmites australis) using optical oxygen sensors. The corresponding carbon dioxide concentrations ([CO2]) were assessed via gas samples from the culms. Highly dynamic diurnal courses of [O2] were recorded, which started at 6.5–13 % in the morning, increased rapidly up to 22 % during midday and declined exponentially during the night. Internal [CO2] were high in the morning (1.55–17.5 %) and decreased (0.04–0.94 %) during the rapid increase of [O2] in the culms. The observed negative correlations between [O2] and [CO2] particularly describe the below ground relationship between plant-mediated oxygen supply and oxygen use by respiration and biogeochemical processes in the rhizosphere. Furthermore, the nocturnal declining slopes of [O2] in culms and rhizomes indicated a down-regulation of the demand for oxygen in the complete below ground plant-associated system. These findings emphasize the need for measurements of plant-internal gas exchange processes under field conditions because it considers the complex interactions in the oxic-anoxic interface. PMID:27207278

Improving medical device regulation: the United States and Europe in perspective.

PubMed

Sorenson, Corinna; Drummond, Michael

2014-03-01

Recent debates and events have brought into question the effectiveness of existing regulatory frameworks for medical devices in the United States and Europe to ensure their performance, safety, and quality. This article provides a comparative analysis of medical device regulation in the two jurisdictions, explores current reforms to improve the existing systems, and discusses additional actions that should be considered to fully meet this aim. Medical device regulation must be improved to safeguard public health and ensure that high-quality and effective technologies reach patients. We explored and analyzed medical device regulatory systems in the United States and Europe in accordance with the available gray and peer-reviewed literature and legislative documents. The two regulatory systems differ in their mandate and orientation, organization, pre- and postmarket evidence requirements, and transparency of process. Despite these differences, both jurisdictions face similar challenges for ensuring that only safe and effective devices reach the market, monitoring real-world use, and exchanging pertinent information on devices with key users such as clinicians and patients. To address these issues, reforms have recently been introduced or debated in the United States and Europe that are principally focused on strengthening regulatory processes, enhancing postmarket regulation through more robust surveillance systems, and improving the traceability and monitoring of devices. Some changes in premarket requirements for devices are being considered. Although the current reforms address some of the outstanding challenges in device regulation, additional steps are needed to improve existing policy. We examine a number of actions to be considered, such as requiring high-quality evidence of benefit for medium- and high-risk devices; moving toward greater centralization and coordination of regulatory approval in Europe; creating links between device identifier systems and existing data collection tools, such as electronic health records; and fostering increased and more effective use of registries to ensure safe postmarket use of new and existing devices. © 2014 Milbank Memorial Fund.

Improving Medical Device Regulation: The United States and Europe in Perspective

PubMed Central

SORENSON, CORINNA; DRUMMOND, MICHAEL

2014-01-01

Context: Recent debates and events have brought into question the effectiveness of existing regulatory frameworks for medical devices in the United States and Europe to ensure their performance, safety, and quality. This article provides a comparative analysis of medical device regulation in the two jurisdictions, explores current reforms to improve the existing systems, and discusses additional actions that should be considered to fully meet this aim. Medical device regulation must be improved to safeguard public health and ensure that high-quality and effective technologies reach patients. Methods: We explored and analyzed medical device regulatory systems in the United States and Europe in accordance with the available gray and peer-reviewed literature and legislative documents. Findings: The two regulatory systems differ in their mandate and orientation, organization, pre-and postmarket evidence requirements, and transparency of process. Despite these differences, both jurisdictions face similar challenges for ensuring that only safe and effective devices reach the market, monitoring real-world use, and exchanging pertinent information on devices with key users such as clinicians and patients. To address these issues, reforms have recently been introduced or debated in the United States and Europe that are principally focused on strengthening regulatory processes, enhancing postmarket regulation through more robust surveillance systems, and improving the traceability and monitoring of devices. Some changes in premarket requirements for devices are being considered. Conclusions: Although the current reforms address some of the outstanding challenges in device regulation, additional steps are needed to improve existing policy. We examine a number of actions to be considered, such as requiring high-quality evidence of benefit for medium-and high-risk devices; moving toward greater centralization and coordination of regulatory approval in Europe; creating links between device identifier systems and existing data collection tools, such as electronic health records; and fostering increased and more effective use of registries to ensure safe postmarket use of new and existing devices. PMID:24597558

Dysregulation of neural calcium signaling in Alzheimer disease, bipolar disorder and schizophrenia

PubMed Central

Berridge, Michael J.

2013-01-01

Neurons have highly developed Ca2+ signaling systems responsible for regulating a large number of neural functions such as the control of brain rhythms, information processing and the changes in synaptic plasticity that underpin learning and memory. The tonic excitatory drive, which is activated by the ascending arousal system, is particularly important for processes such as sensory perception, cognition and consciousness. The Ca2+ signaling pathway is a key component of this arousal system that regulates the neuronal excitability responsible for controlling the neural brain rhythms required for information processing and cognition. Dysregulation of the Ca2+ signaling pathway responsible for many of these neuronal processes has been implicated in the development of some of the major neural diseases in man such as Alzheimer disease, bipolar disorder and schizophrenia. Various treatments, which are known to act by reducing the activity of Ca2+ signaling, have proved successful in alleviating the symptoms of some of these neural diseases. PMID:22895098

Mentalized affectivity: A new model and assessment of emotion regulation

PubMed Central

Kolasi, Jonela; Hegsted, Camilla P.; Berkowitz, Yoni; Jurist, Elliot L.

2017-01-01

Here we introduce a new assessment of emotion regulation called the Mentalized Affectivity Scale (MAS). A large online adult sample (N = 2,840) completed the 60-item MAS along with a battery of psychological measures. Results revealed a robust three-component structure underlying mentalized affectivity, which we labeled: Identifying emotions (the ability to identify emotions and to reflect on the factors that influence them); Processing emotions (the ability to modulate and distinguish complex emotions); and Expressing emotions (the tendency to express emotions outwardly or inwardly). Hierarchical modeling suggested that Processing emotions delineates from Identifying them, and Expressing emotions delineates from Processing them. We then showed how these components are associated with personality traits, well-being, trauma, and 18 different psychological disorders (including mood, neurological, and personality disorders). Notably, those with anxiety, mood, and personality disorders showed a profile of high Identifying and low Processing compared to controls. Further, results showed how mentalized affectivity scores varied across psychological treatment modalities and years spent in therapy. Taken together, the model of mentalized affectivity advances prior theory and research on emotion regulation and the MAS is a useful and reliable instrument that can be used in both clinical and non-clinical settings in psychology, psychiatry, and neuroscience. PMID:29045403

Making Memories Matter

PubMed Central

Gold, Paul E.; Korol, Donna L.

2012-01-01

This article reviews some of the neuroendocrine bases by which emotional events regulate brain mechanisms of learning and memory. In laboratory rodents, there is extensive evidence that epinephrine influences memory processing through an inverted-U relationship, at which moderate levels enhance and high levels impair memory. These effects are, in large part, mediated by increases in blood glucose levels subsequent to epinephrine release, which then provide support for the brain processes engaged by learning and memory. These brain processes include augmentation of neurotransmitter release and of energy metabolism, the latter apparently including a key role for astrocytic glycogen. In addition to up- and down-regulation of learning and memory in general, physiological concomitants of emotion and arousal can also switch the neural system that controls learning at a particular time, at once improving some attributes of learning and impairing others in a manner that results in a change in the strategy used to solve a problem. PMID:23264764

Maf1 Protein, Repressor of RNA Polymerase III, Indirectly Affects tRNA Processing*

PubMed Central

Karkusiewicz, Iwona; Turowski, Tomasz W.; Graczyk, Damian; Towpik, Joanna; Dhungel, Nripesh; Hopper, Anita K.; Boguta, Magdalena

2011-01-01

Maf1 is negative regulator of RNA polymerase III in yeast. We observed high levels of both primary transcript and end-matured, intron-containing pre-tRNAs in the maf1Δ strain. This pre-tRNA accumulation could be overcome by transcription inhibition, arguing against a direct role of Maf1 in tRNA maturation and suggesting saturation of processing machinery by the increased amounts of primary transcripts. Saturation of the tRNA exportin, Los1, is one reason why end-matured intron-containing pre-tRNAs accumulate in maf1Δ cells. However, it is likely possible that other components of the processing pathway are also limiting when tRNA transcription is increased. According to our model, Maf1-mediated transcription control and nuclear export by Los1 are two major stages of tRNA biosynthesis that are regulated by environmental conditions in a coordinated manner. PMID:21940626

Maf1 protein, repressor of RNA polymerase III, indirectly affects tRNA processing.

PubMed

Karkusiewicz, Iwona; Turowski, Tomasz W; Graczyk, Damian; Towpik, Joanna; Dhungel, Nripesh; Hopper, Anita K; Boguta, Magdalena

2011-11-11

Maf1 is negative regulator of RNA polymerase III in yeast. We observed high levels of both primary transcript and end-matured, intron-containing pre-tRNAs in the maf1Δ strain. This pre-tRNA accumulation could be overcome by transcription inhibition, arguing against a direct role of Maf1 in tRNA maturation and suggesting saturation of processing machinery by the increased amounts of primary transcripts. Saturation of the tRNA exportin, Los1, is one reason why end-matured intron-containing pre-tRNAs accumulate in maf1Δ cells. However, it is likely possible that other components of the processing pathway are also limiting when tRNA transcription is increased. According to our model, Maf1-mediated transcription control and nuclear export by Los1 are two major stages of tRNA biosynthesis that are regulated by environmental conditions in a coordinated manner.

Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency

PubMed Central

Cacchiarelli, Davide; Trapnell, Cole; Ziller, Michael J.; Soumillon, Magali; Cesana, Marcella; Karnik, Rahul; Donaghey, Julie; Smith, Zachary D.; Ratanasirintrawoot, Sutheera; Zhang, Xiaolan; Ho Sui, Shannan J.; Wu, Zhaoting; Akopian, Veronika; Gifford, Casey A.; Doench, John; Rinn, John L.; Daley, George Q.; Meissner, Alexander; Lander, Eric S.; Mikkelsen, Tarjei S.

2015-01-01

Summary Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered reactivation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. PMID:26186193

APP intracellular domain derived from amyloidogenic β- and γ-secretase cleavage regulates neprilysin expression

PubMed Central

Grimm, Marcus O. W.; Mett, Janine; Stahlmann, Christoph P.; Grösgen, Sven; Haupenthal, Viola J.; Blümel, Tamara; Hundsdörfer, Benjamin; Zimmer, Valerie C.; Mylonas, Nadine T.; Tanila, Heikki; Müller, Ulrike; Grimm, Heike S.; Hartmann, Tobias

2015-01-01

Alzheimer's disease (AD) is characterized by an accumulation of Amyloid-β (Aβ), released by sequential proteolytic processing of the amyloid precursor protein (APP) by β - and γ-secretase. Aβ peptides can aggregate, leading to toxic Aβ oligomers and amyloid plaque formation. Aβ accumulation is not only dependent on de novo synthesis but also on Aβ degradation. Neprilysin (NEP) is one of the major enzymes involved in Aβ degradation. Here we investigate the molecular mechanism of NEP regulation, which is up to now controversially discussed to be affected by APP processing itself. We found that NEP expression is highly dependent on the APP intracellular domain (AICD), released by APP processing. Mouse embryonic fibroblasts devoid of APP processing, either by the lack of the catalytically active subunit of the γ-secretase complex [presenilin (PS) 1/2] or by the lack of APP and the APP-like protein 2 (APLP2), showed a decreased NEP expression, activity and protein level. Similar results were obtained by utilizing cells lacking a functional AICD domain (APPΔCT15) or expressing mutations in the genes encoding for PS1. AICD supplementation or retransfection with an AICD encoding plasmid could rescue the down-regulation of NEP further strengthening the link between AICD and transcriptional NEP regulation, in which Fe65 acts as an important adaptor protein. Especially AICD generated by the amyloidogenic pathway seems to be more involved in the regulation of NEP expression. In line, analysis of NEP gene expression in vivo in six transgenic AD mouse models (APP and APLP2 single knock-outs, APP/APLP2 double knock-out, APP-swedish, APP-swedish/PS1Δexon9, and APPΔCT15) confirmed the results obtained in cell culture. In summary, in the present study we clearly demonstrate an AICD-dependent regulation of the Aβ-degrading enzyme NEP in vitro and in vivo and elucidate the underlying mechanisms that might be beneficial to develop new therapeutic strategies for the treatment of AD. PMID:26074811

Transcriptome Response Mediated by Cold Stress in Lotus japonicus.

PubMed

Calzadilla, Pablo I; Maiale, Santiago J; Ruiz, Oscar A; Escaray, Francisco J

2016-01-01

Members of the Lotus genus are important as agricultural forage sources under marginal environmental conditions given their high nutritional value and tolerance of various abiotic stresses. However, their dry matter production is drastically reduced in cooler seasons, while their response to such conditions is not well studied. This paper analyzes cold acclimation of the genus by studying Lotus japonicus over a stress period of 24 h. High-throughput RNA sequencing was used to identify and classify 1077 differentially expressed genes, of which 713 were up-regulated and 364 were down-regulated. Up-regulated genes were principally related to lipid, cell wall, phenylpropanoid, sugar, and proline regulation, while down-regulated genes affected the photosynthetic process and chloroplast development. Together, a total of 41 cold-inducible transcription factors were identified, including members of the AP2/ERF, NAC, MYB, and WRKY families; two of them were described as putative novel transcription factors. Finally, DREB1/CBFs were described with respect to their cold stress expression profiles. This is the first transcriptome profiling of the model legume L. japonicus under cold stress. Data obtained may be useful in identifying candidate genes for breeding modified species of forage legumes that more readily acclimate to low temperatures.

Alternative Fuels Data Center: Ethanol Vehicle Emissions

Science.gov Websites

Availability Conversions Emissions Laws & Incentives Ethanol Vehicle Emissions When blended with gasoline emissions of regulated pollutants, toxic chemicals, and greenhouse gases (GHGs). The use of high-level extraction, processing, manufacturing, distribution, use, and disposal or recycling. When comparing fuels, a

DETERMINING THE ECONOMIC VALUE OF IMPROVED HUMAN EXPOSURE DATA

EPA Science Inventory

The U.S. EPA develops and revises environmental regulations and policies to protect the environment and human health. One of the key components of the regulatory process is establishing the proposed action level, which requires high quality exposure data. In many cases, expos...

Cognitive Control and Conflict Adaptation in Youth with High-Functioning Autism

ERIC Educational Resources Information Center

Larson, Michael J.; South, Mikle; Clayson, Peter E.; Clawson, Ann

2012-01-01

Background: Youth diagnosed with autism spectrum disorders (ASD) often show deficits in cognitive control processes, potentially contributing to characteristic difficulties monitoring and regulating behavior. Modification of performance following conflict can be measured by examining conflict adaptation, the adjustment of cognitive resources based…

40 CFR 63.982 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., transfer racks, and equipment leaks. An owner or operator who is referred to this subpart for controlling regulated material emissions from storage vessels, process vents, low and high throughput transfer racks, or... racks. (i) For low throughput transfer racks, the owner or operator shall comply with the applicable...

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

Liu, Xing; Xu, Yanli; Meng, Qian

Colorectal cancer (CRC) is one of the most common types of malignant tumor worldwide. Currently, although many researchers have been devoting themselves in CRC studies, the process of locating biomarkers for CRC early diagnosis and prognostic is still very slow. Using a centrifugal proteomic reactor-based proteomic analysis of minute amount of colonic biopsies by enteroscopy sampling, 2620 protein groups were quantified between cancer mucosa and adjacent normal colorectal mucosa. Of which, 403 protein groups were differentially expressed with statistic significance between cancer and normal tissues, including 195 up-regulated and 208 down-regulated proteins in cancer tissues. Three proteins (SOD3, PRELP andmore » NGAL) were selected for further Western blot validation. And the resulting Western blot experimental results were consistent with the quantitative proteomic data. SOD3 and PRELP are down-regulated in CRC mucosa comparing to adjacent normal tissue, while NGAL is up-regulated in CRC mucosa. In conclusion, the centrifugal proteomic reactor-based label-free quantitative proteomic approach provides a highly sensitive and powerful tool for analyzing minute protein sample from tiny colorectal biopsies, which may facilitate CRC biomarkers discovery for diagnoses and prognoses. -- Highlights: •Minute amount of colonic biopsies by endoscopy is suitable for proteomic analysis. •Centrifugal proteomic reactor can be used for processing tiny clinic biopsy sample. •SOD3 and PRELP are down-regulated in CRC, while NGAL is up-regulated in CRC.« less

The Significance of an Enhanced Concept of the Organism for Medicine

PubMed Central

2016-01-01

Recent developments in evolutionary biology, comparative embryology, and systems biology suggest the necessity of a conceptual shift in the way we think about organisms. It is becoming increasingly evident that molecular and genetic processes are subject to extremely refined regulation and control by the cell and the organism, so that it becomes hard to define single molecular functions or certain genes as primary causes of specific processes. Rather, the molecular level is integrated into highly regulated networks within the respective systems. This has consequences for medical research in general, especially for the basic concept of personalized medicine or precision medicine. Here an integrative systems concept is proposed that describes the organism as a multilevel, highly flexible, adaptable, and, in this sense, autonomous basis for a human individual. The hypothesis is developed that these properties of the organism, gained from scientific observation, will gradually make it necessary to rethink the conceptual framework of physiology and pathophysiology in medicine. PMID:27446221

Explicit and Implicit Emotion Regulation: A Dual-Process Framework

PubMed Central

Gyurak, Anett; Gross, James J.; Etkin, Amit

2012-01-01

It is widely acknowledged that emotions can be regulated in an astonishing variety of ways. Most research to date has focused on explicit (effortful) forms of emotion regulation. However, there is growing research interest in implicit (automatic) forms of emotion regulation. To organize emerging findings, we present a dual-process framework that integrates explicit and implicit forms of emotion regulation, and argue that both forms of regulation are necessary for well-being. In the first section of this review, we provide a broad overview of the construct of emotion regulation, with an emphasis on explicit and implicit processes. In the second section, we focus on explicit emotion regulation, considering both neural mechanisms that are associated with these processes and their experiential and physiological consequences. In the third section, we turn to several forms of implicit emotion regulation, and integrate the burgeoning literature in this area. We conclude by outlining open questions and areas for future research. PMID:21432682

Self-regulated learning processes of medical students during an academic learning task.

PubMed

Gandomkar, Roghayeh; Mirzazadeh, Azim; Jalili, Mohammad; Yazdani, Kamran; Fata, Ladan; Sandars, John

2016-10-01

This study was designed to identify the self-regulated learning (SRL) processes of medical students during a biomedical science learning task and to examine the associations of the SRL processes with previous performance in biomedical science examinations and subsequent performance on a learning task. A sample of 76 Year 1 medical students were recruited based on their performance in biomedical science examinations and stratified into previous high and low performers. Participants were asked to complete a biomedical science learning task. Participants' SRL processes were assessed before (self-efficacy, goal setting and strategic planning), during (metacognitive monitoring) and after (causal attributions and adaptive inferences) their completion of the task using an SRL microanalytic interview. Descriptive statistics were used to analyse the means and frequencies of SRL processes. Univariate and multiple logistic regression analyses were conducted to examine the associations of SRL processes with previous examination performance and the learning task performance. Most participants (from 88.2% to 43.4%) reported task-specific processes for SRL measures. Students who exhibited higher self-efficacy (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.09-1.90) and reported task-specific processes for metacognitive monitoring (OR 6.61, 95% CI 1.68-25.93) and causal attributions (OR 6.75, 95% CI 2.05-22.25) measures were more likely to be high previous performers. Multiple analysis revealed that similar SRL measures were associated with previous performance. The use of task-specific processes for causal attributions (OR 23.00, 95% CI 4.57-115.76) and adaptive inferences (OR 27.00, 95% CI 3.39-214.95) measures were associated with being a high learning task performer. In multiple analysis, only the causal attributions measure was associated with high learning task performance. Self-efficacy, metacognitive monitoring and causal attributions measures were associated positively with previous performance. Causal attributions and adaptive inferences measures were associated positively with learning task performance. These findings may inform remediation interventions in the early years of medical school training. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Transcriptional master regulator analysis in breast cancer genetic networks.

PubMed

Tovar, Hugo; García-Herrera, Rodrigo; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique

2015-12-01

Gene regulatory networks account for the delicate mechanisms that control gene expression. Under certain circumstances, gene regulatory programs may give rise to amplification cascades. Such transcriptional cascades are events in which activation of key-responsive transcription factors called master regulators trigger a series of gene expression events. The action of transcriptional master regulators is then important for the establishment of certain programs like cell development and differentiation. However, such cascades have also been related with the onset and maintenance of cancer phenotypes. Here we present a systematic implementation of a series of algorithms aimed at the inference of a gene regulatory network and analysis of transcriptional master regulators in the context of primary breast cancer cells. Such studies were performed in a highly curated database of 880 microarray gene expression experiments on biopsy-captured tissue corresponding to primary breast cancer and healthy controls. Biological function and biochemical pathway enrichment analyses were also performed to study the role that the processes controlled - at the transcriptional level - by such master regulators may have in relation to primary breast cancer. We found that transcription factors such as AGTR2, ZNF132, TFDP3 and others are master regulators in this gene regulatory network. Sets of genes controlled by these regulators are involved in processes that are well-known hallmarks of cancer. This kind of analyses may help to understand the most upstream events in the development of phenotypes, in particular, those regarding cancer biology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Arabidopsis and Tobacco SUPERMAN regulate hormone signalling and mediate cell proliferation and differentiation

PubMed Central

Nibau, Candida; Di Stilio, Verónica S.; Wu, Hen-ming; Cheung, Alice Y.

2011-01-01

Arabidopsis thaliana SUPERMAN (SUP) plays an important role during flower development by maintaining the boundary between stamens and carpels in the inner two whorls. It was proposed that SUP maintains this boundary by regulating cell proliferation in both whorls, as loss-of-function superman mutants produce more stamens at the expense of carpels. However, the cellular mechanism that underlies SUP function remains unknown. Here Arabidopsis or tobacco (Nicotiana tabacum) SUP was overexpressed in tobacco plants to substantiate SUP's role as a regulator of cell proliferation and boundary definition and provide evidence that its biological role may be mediated via hormonal changes. It was found that moderate levels of SUP stimulated cell growth and proliferation, whereas high levels were inhibitory. SUP stimulated auxin- and cytokinin-regulated processes, and cells overexpressing SUP displayed reduced hormone dependency for proliferation and regeneration into plants. SUP also induced proliferation of female traits in the second and third flower whorls and promoted differentiation of petaloid properties in sepals, further supporting a role for SUP as a boundary regulator. Moreover, cytokinin suppressed stamen development and promoted differentiation of carpeloid tissues, suggesting that SUP may regulate male and female development via its effect on cytokinin signalling. Taken together, these observations suggest a model whereby the effect of SUP on cell growth and proliferation involves the modulation of auxin- and cytokinin-regulated processes. Furthermore, differential SUP expression or different sensitivities of different cell types to SUP may determine whether SUP stimulates or suppresses their proliferation. PMID:20980362

Gap Junctions

PubMed Central

Nielsen, Morten Schak; Axelsen, Lene Nygaard; Sorgen, Paul L.; Verma, Vandana; Delmar, Mario; Holstein-Rathlou, Niels-Henrik

2013-01-01

Gap junctions are essential to the function of multicellular animals, which require a high degree of coordination between cells. In vertebrates, gap junctions comprise connexins and currently 21 connexins are known in humans. The functions of gap junctions are highly diverse and include exchange of metabolites and electrical signals between cells, as well as functions, which are apparently unrelated to intercellular communication. Given the diversity of gap junction physiology, regulation of gap junction activity is complex. The structure of the various connexins is known to some extent; and structural rearrangements and intramolecular interactions are important for regulation of channel function. Intercellular coupling is further regulated by the number and activity of channels present in gap junctional plaques. The number of connexins in cell-cell channels is regulated by controlling transcription, translation, trafficking, and degradation; and all of these processes are under strict control. Once in the membrane, channel activity is determined by the conductive properties of the connexin involved, which can be regulated by voltage and chemical gating, as well as a large number of posttranslational modifications. The aim of the present article is to review our current knowledge on the structure, regulation, function, and pharmacology of gap junctions. This will be supported by examples of how different connexins and their regulation act in concert to achieve appropriate physiological control, and how disturbances of connexin function can lead to disease. © 2012 American Physiological Society. Compr Physiol 2:1981-2035, 2012. PMID:23723031

F-box only protein 2 (Fbxo2) regulates amyloid precursor protein levels and processing.

PubMed

Atkin, Graham; Hunt, Jack; Minakawa, Eiko; Sharkey, Lisa; Tipper, Nathan; Tennant, William; Paulson, Henry L

2014-03-07

The amyloid precursor protein (APP) is an integral membrane glycoprotein whose cleavage products, particularly amyloid-β, accumulate in Alzheimer disease (AD). APP is present at synapses and is thought to play a role in both the formation and plasticity of these critical neuronal structures. Despite the central role suggested for APP in AD pathogenesis, the mechanisms regulating APP in neurons and its processing into cleavage products remain incompletely understood. F-box only protein 2 (Fbxo2), a neuron-enriched ubiquitin ligase substrate adaptor that preferentially binds high-mannose glycans on glycoproteins, was previously implicated in APP processing by facilitating the degradation of the APP-cleaving β-secretase, β-site APP-cleaving enzyme. Here, we sought to determine whether Fbxo2 plays a similar role for other glycoproteins in the amyloid processing pathway. We present in vitro and in vivo evidence that APP is itself a substrate for Fbxo2. APP levels were decreased in the presence of Fbxo2 in non-neuronal cells, and increased in both cultured hippocampal neurons and brain tissue from Fbxo2 knock-out mice. The processing of APP into its cleavage products was also increased in hippocampi and cultured hippocampal neurons lacking Fbxo2. In hippocampal slices, this increase in cleavage products was accompanied by a significant reduction in APP at the cell surface. Taken together, these results suggest that Fbxo2 regulates APP levels and processing in the brain and may play a role in modulating AD pathogenesis.

Expressed microRNA associated with high rate of egg production in chicken ovarian follicles.

PubMed

Wu, N; Gaur, U; Zhu, Q; Chen, B; Xu, Z; Zhao, X; Yang, M; Li, D

2017-04-01

MicroRNA (miRNA) is a highly conserved class of small noncoding RNA about 19-24 nucleotides in length that function in a specific manner to post-transcriptionally regulate gene expression in organisms. Tissue miRNA expression studies have discovered a myriad of functions for miRNAs in various aspects, but a role for miRNAs in chicken ovarian tissue at 300 days of age has not hitherto been reported. In this study, we performed the first miRNA analysis of ovarian tissues in chickens with low and high rates of egg production using high-throughput sequencing. By comparing low rate of egg production chickens with high rate of egg production chickens, 17 significantly differentially expressed miRNAs were found (P < 0.05), including 11 known and six novel miRNAs. We found that all 11 known miRNAs were involved mainly in pathways of reproduction regulation, such as steroid hormone biosynthesis and dopaminergic synapse. Additionally, expression profiling of six randomly selected differentially regulated miRNAs were validated by quantitative real-time polymerase chain reaction (RT-qPCR). Some miRNAs, such as gga-miR-34b, gga-miR-34c and gga-miR-216b, were reported to regulate processes such as proliferation, cell cycle, apoptosis and metastasis and were expressed differentially in ovaries of chickens with high rates of egg production, suggesting that these miRNAs have an important role in ovary development and reproductive management of chicken. Furthermore, we uncovered that a significantly up-regulated miRNA-gga-miR-200a-3p-is ubiquitous in reproduction-regulation-related pathways. This miRNA may play a special central role in the reproductive management of chicken, and needs to be further studied for confirmation. © 2016 Stichting International Foundation for Animal Genetics.

Emotion regulation difficulties, youth-adult relationships, and suicide attempts among high school students in underserved communities.

PubMed

Pisani, Anthony R; Wyman, Peter A; Petrova, Mariya; Schmeelk-Cone, Karen; Goldston, David B; Xia, Yinglin; Gould, Madelyn S

2013-06-01

To develop and refine interventions to prevent youth suicide, knowledge is needed about specific processes that reduce risk at a population level. Using a cross-sectional design, the present study tested hypotheses regarding associations between self-reported suicide attempts, emotion regulation difficulties, and positive youth-adult relationships among 7,978 high-school students (48.6% male, 49.9% female) in 30 high schools from predominantly rural, low-income communities. 683 students (8.6%) reported a past-year suicide attempt. Emotion regulation difficulties and a lack of trusted adults at home and school were associated with increased risk for making a past-year suicide attempt, above and beyond the effects of depressive symptoms and demographic factors. The association between emotion regulation difficulties and suicide attempts was modestly lower among students who perceived themselves as having higher levels of trusted adults in the family, consistent with a protective effect. Having a trusted adult in the community (outside of school and family) was associated with fewer suicide attempts in models that controlled only for demographic covariates, but not when taking symptoms of depression into account. These findings point to adolescent emotion regulation and relationships with trusted adults as complementary targets for suicide prevention that merit further intervention studies. Reaching these targets in a broad population of adolescents will require new delivery systems and "option rich" (OR) intervention designs.

Emotion Regulation Difficulties, Youth-Adult Relationships, and Suicide Attempts Among High School Students in Underserved Communities

PubMed Central

Pisani, Anthony R.; Wyman, Peter A.; Petrova, Mariya; Schmeelk-Cone, Karen; Goldston, David B.; Xia, Yinglin; Gould, Madelyn S.

2013-01-01

To develop and refine interventions to prevent youth suicide, knowledge is needed about specific processes that reduce risk at a population level. Using a cross-sectional design, the present study tested hypotheses regarding associations between self-reported suicide attempts, emotion regulation difficulties, and positive youth-adult relationships among 7,978 high-school students (48.6% male, 49.9% female) in 30 high schools from predominantly rural, low-income communities. 683 students (8.6%) reported a past-year suicide attempt. Emotion regulation difficulties and a lack of trusted adults at home and school were associated with increased risk for making a past-year suicide attempt, above and beyond the effects of depressive symptoms and demographic factors. The association between emotion regulation difficulties and suicide attempts was modestly lower among students who perceived themselves as having higher levels of trusted adults in the family, consistent with a protective effect. Having a trusted adult in the community (outside of school and family) was associated with fewer suicide attempts in models that controlled only for demographic covariates, but not when taking symptoms of depression into account. These findings point to adolescent emotion regulation and relationships with trusted adults as complementary targets for suicide prevention that merit further intervention studies. Reaching these targets in a broad population of adolescents will require new delivery systems and “option rich” intervention designs. PMID:23666604

Redox-related metabolites and gene expression modulated by sugar in sunflower leaves: similarities with Sunflower chlorotic mottle virus-induced symptom.

PubMed

Rodríguez, Marianela; Muñoz, Nacira; Lenardon, Sergio; Lascano, Ramiro

2013-01-01

Sugars are part of an integrated redox system, since they are key regulators of respiration and photosynthesis, and therefore of the levels of reducing power, ATP and ROS. These elements are major determinants of the cellular redox state, which is involved in the perception and regulation of many endogenous and environmental stimuli. Our previous findings suggested that early sugar increase produced during compatible Sunflower chlorotic mottle virus (SuCMoV) infection might modulate chlorotic symptom development through redox state alteration in sunflower. The purpose of this work was to characterize redox-related metabolites and gene expression changes associated with high sugar availability and symptom development induced by SuCMoV. The results show that sugar caused an increase in glutathione, ascorbate, pyridine nucleotides, and ATP. In addition, higher sugar availability reduced hydrogen peroxide and ΦPSII. This finding suggests that high sugar availability would be associated with cellular redox alteration and photoinhibitory process. The expression of the genes analyzed was also strongly affected by sugar, such as the down-regulation of psbA and up-regulation of psbO and cp29. The expression level of cytoplasmic (apx-1 and gr)- and chloroplastic (Fe-sod)-targeted genes was also significantly enhanced in sugar-treated leaves. Therefore, all these responses suggest that sugars induce chloroplastic redox state alteration with photoinhibition process that could be contributing to chlorotic symptom development during SuCMoV infection.

Regulation of water balance in mangroves.

PubMed

Reef, Ruth; Lovelock, Catherine E

2015-02-01

Mangroves are a group of highly salt-tolerant woody plants. The high water use efficiency of mangroves under saline conditions suggests that regulation of water transport is a crucial component of their salinity tolerance. This review focuses on the processes that contribute to the ability of mangroves to maintain water uptake and limit water loss to the soil and the atmosphere under saline conditions, from micro to macro scales. These processes include: (1) efficient filtering of the incoming water to exclude salt; (2) maintenance of internal osmotic potentials lower than that of the rhizosphere; (3) water-saving properties; and (4) efficient exploitation of less-saline water sources when these become available. Mangroves are inherently plastic and can change their structure at the root, leaf and stand levels in response to salinity in order to exclude salt from the xylem stream, maintain leaf hydraulic conductance, avoid cavitation and regulate water loss (e.g. suberization of roots and alterations of leaf size, succulence and angle, hydraulic anatomy and biomass partitioning). However, much is still unknown about the regulation of water uptake in mangroves, such as how they sense and respond to heterogeneity in root zone salinity, the extent to which they utilize non-stomatally derived CO2 as a water-saving measure and whether they can exploit atmospheric water sources. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

17β-Estradiol regulates cell proliferation, colony formation, migration, invasion and promotes apoptosis by upregulating miR-9 and thus degrades MALAT-1 in osteosarcoma cell MG-63 in an estrogen receptor-independent manner

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

Fang, Dengfeng; Yang, Hui; Lin, Jing

2015-02-20

In bone, different concentration of estrogen leads to various of physiological processes in osteoblast, such as the proliferation, migration, and apoptosis in an estrogen receptor-dependent manner. But little was known about the estrogen effects on osteosarcoma (OS). In this study, OS cell MG-63 was treated with low (1 nM) or high (100 nM) dose of 17β-Estradiol (E2) with the presence or absence of estrogen receptor α (ERα), for evaluating the E2 effects on proliferation, migration, invasion, colony formation and apoptosis. Consistent with a previous study, high dose of E2 treatment dramatically downregulated expressing level of long non-coding RNA metastasis associated lung adenocarcinomamore » transcript 1 (MALAT-1). The observation of upregulation of miR-9 after a high dose of E2 treatment indicated the cause of MALAT-1 reduction. Downregulation of MALAT-1 promoted the combination of SFPQ/PTBP2 complex. It was also observed that the proliferation, migration, invasion, colony formation and apoptosis of OS cells were remarkably affected by high dose of E2 treatment, but not by low dose, in an ERα independent manner. Furthermore, the abolishment of the effects on these physiological processes caused by ectopic expression of miR-9 ASOs suggested the necessity of miR-9 in MALAT-1 regulation. Here we found that the high dose of E2 treatment upregulated miR-9 thus posttranscriptionally regulated MALAT-1 RNA level in OS cells, and then the downregulation of MALAT-1 inhibited cell proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) processes in the E2-dose dependent and ER-independent ways. - Highlights: • E2 affects osteosarcoma cell MG-63 in an Estrogen receptor-independent way. • High dose of E2 treatment upregulates miR-9 which target to MALAT-1 RNA. • Upregulated miR-9 degrades MALAT-1 and thus affects combination of SFPQ/PTBP2. • E2 treatment block cell proliferation, colony formation, mobility, and enhance apoptosis.« less

Gene regulation is governed by a core network in hepatocellular carcinoma.

PubMed

Gu, Zuguang; Zhang, Chenyu; Wang, Jin

2012-05-01

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, and the mechanisms that lead to the disease are still relatively unclear. However, with the development of high-throughput technologies it is possible to gain a systematic view of biological systems to enhance the understanding of the roles of genes associated with HCC. Thus, analysis of the mechanism of molecule interactions in the context of gene regulatory networks can reveal specific sub-networks that lead to the development of HCC. In this study, we aimed to identify the most important gene regulations that are dysfunctional in HCC generation. Our method for constructing gene regulatory network is based on predicted target interactions, experimentally-supported interactions, and co-expression model. Regulators in the network included both transcription factors and microRNAs to provide a complete view of gene regulation. Analysis of gene regulatory network revealed that gene regulation in HCC is highly modular, in which different sets of regulators take charge of specific biological processes. We found that microRNAs mainly control biological functions related to mitochondria and oxidative reduction, while transcription factors control immune responses, extracellular activity and the cell cycle. On the higher level of gene regulation, there exists a core network that organizes regulations between different modules and maintains the robustness of the whole network. There is direct experimental evidence for most of the regulators in the core gene regulatory network relating to HCC. We infer it is the central controller of gene regulation. Finally, we explored the influence of the core gene regulatory network on biological pathways. Our analysis provides insights into the mechanism of transcriptional and post-transcriptional control in HCC. In particular, we highlight the importance of the core gene regulatory network; we propose that it is highly related to HCC and we believe further experimental validation is worthwhile.

The integration of the risk management process with the lifecycle of medical device software.

PubMed

Pecoraro, F; Luzi, D

2014-01-01

The application of software in the Medical Device (MD) domain has become central to the improvement of diagnoses and treatments. The new European regulations that specifically address software as an important component of MD, require complex procedures to make software compliant with safety requirements, introducing thereby new challenges in the qualification and classification of MD software as well as in the performance of risk management activities. Under this perspective, the aim of this paper is to propose an integrated framework that combines the activities to be carried out by the manufacturer to develop safe software within the development lifecycle based on the regulatory requirements reported in US and European regulations as well as in the relevant standards and guidelines. A comparative analysis was carried out to identify the main issues related to the application of the current new regulations. In addition, standards and guidelines recently released to harmonise procedures for the validation of MD software have been used to define the risk management activities to be carried out by the manufacturer during the software development process. This paper highlights the main issues related to the qualification and classification of MD software, providing an analysis of the different regulations applied in Europe and the US. A model that integrates the risk management process within the software development lifecycle has been proposed too. It is based on regulatory requirements and considers software risk analysis as a central input to be managed by the manufacturer already at the initial stages of the software design, in order to prevent MD failures. Relevant changes in the process of MD development have been introduced with the recognition of software being an important component of MDs as stated in regulations and standards. This implies the performance of highly iterative processes that have to integrate the risk management in the framework of software development. It also makes it necessary to involve both medical and software engineering competences to safeguard patient and user safety.

A High Performance 50% Clock Duty Cycle Regulator

NASA Astrophysics Data System (ADS)

Huang, Peng; Deng, Hong-Hui; Yin, Yong-Sheng

A low-jitter clock duty cycle corrector circuit applied in high performance ADC is presented in the paper, such circuits can change low accuracy input signals with different frequencies into 50% pulse width clock. The result have show that the circuit could lock duty cycle rapidly with an accuracy of 50% ± 1% in 200ns. This circuit have 10%-90% of duty cycle input, and clock jitter could be suppressed to less than 5ps. The method used in the circuit, which provides little relationship with the noise and process mismatch, is widely used Implemented in 0.18μm CMOS process.

UVA and UVB Irradiation Differentially Regulate microRNA Expression in Human Primary Keratinocytes

PubMed Central

Kraemer, Anne; Chen, I-Peng; Henning, Stefan; Faust, Alexandra; Volkmer, Beate; Atkinson, Michael J.; Moertl, Simone; Greinert, Ruediger

2013-01-01

MicroRNA (miRNA)-mediated regulation of the cellular transcriptome is an important epigenetic mechanism for fine-tuning regulatory pathways. These include processes related to skin cancer development, progression and metastasis. However, little is known about the role of microRNA as an intermediary in the carcinogenic processes following exposure to UV-radiation. We now show that UV irradiation of human primary keratinocytes modulates the expression of several cellular miRNAs. A common set of miRNAs was influenced by exposure to both UVA and UVB. However, each wavelength band also activated a distinct subset of miRNAs. Common sets of UVA- and UVB-regulated miRNAs harbor the regulatory elements GLYCA-nTRE, GATA-1-undefined-site-13 or Hox-2.3-undefined-site-2 in their promoters. In silico analysis indicates that the differentially expressed miRNAs responding to UV have potential functions in the cellular pathways of cell growth and proliferation. Interestingly, the expression of miR-23b, which is a differentiation marker of human keratinocytes, is remarkably up-regulated after UVA irradiation. Studying the interaction between miR-23b and its putative skin-relevant targets using a Luciferase reporter assay revealed that RRAS2 (related RAS viral oncogene homolog 2), which is strongly expressed in highly aggressive malignant skin cancer, to be a direct target of miR-23b. This study demonstrates for the first time a differential miRNA response to UVA and UVB in human primary keratinocytes. This suggests that selective regulation of signaling pathways occurs in response to different UV energies. This may shed new light on miRNA-regulated carcinogenic processes involved in UV-induced skin carcinogenesis. PMID:24391759

Regulation of cardiac excitation and contraction by p21 activated kinase-1.

PubMed

Ke, Yunbo; Lei, Ming; Solaro, R John

2008-01-01

Cardiac excitation and contraction are regulated by a variety of signaling molecules. Central to the regulatory scheme are protein kinases and phosphatases that carry out reversible phosphorylation of different effectors. The process of beta-adrenergic stimulation mediated by cAMP dependent protein kinase (PKA) forms a well-known pathway considered as the most significant control mechanism in excitation and contraction as well as many other regulatory mechanisms in cardiac function. However, although dephosphorylation pathways are critical to these regulatory processes, signaling to phosphatases is relatively poorly understood. Emerging evidence indicates that regulation of phosphatases, which dampen the effect of beta-adrenergic stimulation, is also important. We review here functional studies of p21 activated kinase-1 (Pak1) and its potential role as an upstream signal for protein phosphatase PP2A in the heart. Pak1 is a serine/threonine protein kinase directly activated by the small GTPases Cdc42 and Rac1. Pak1 is highly expressed in different regions of the heart and modulates the activities of ion channels, sarcomeric proteins, and other phosphoproteins through up-regulation of PP2A activity. Coordination of Pak1 and PP2A activities is not only potentially involved in regulation of normal cardiac function, but is likely to be important in patho-physiological conditions.

Childhood trauma exposure disrupts the automatic regulation of emotional processing.

PubMed

Marusak, Hilary A; Martin, Kayla R; Etkin, Amit; Thomason, Moriah E

2015-03-13

Early-life trauma is one of the strongest risk factors for later emotional psychopathology. Although research in adults highlights that childhood trauma predicts deficits in emotion regulation that persist decades later, it is unknown whether neural and behavioral changes that may precipitate illness are evident during formative, developmental years. This study examined whether automatic regulation of emotional conflict is perturbed in a high-risk urban sample of trauma-exposed children and adolescents. A total of 14 trauma-exposed and 16 age-, sex-, and IQ-matched comparison youth underwent functional MRI while performing an emotional conflict task that involved categorizing facial affect while ignoring an overlying emotion word. Engagement of the conflict regulation system was evaluated at neural and behavioral levels. Results showed that trauma-exposed youth failed to dampen dorsolateral prefrontal cortex activity and engage amygdala-pregenual cingulate inhibitory circuitry during the regulation of emotional conflict, and were less able to regulate emotional conflict. In addition, trauma-exposed youth showed greater conflict-related amygdala reactivity that was associated with diminished levels of trait reward sensitivity. These data point to a trauma-related deficit in automatic regulation of emotional processing, and increase in sensitivity to emotional conflict in neural systems implicated in threat detection. Aberrant amygdala response to emotional conflict was related to diminished reward sensitivity that is emerging as a critical stress-susceptibility trait that may contribute to the emergence of mental illness during adolescence. These results suggest that deficits in conflict regulation for emotional material may underlie heightened risk for psychopathology in individuals that endure early-life trauma.

Harnessing Proteasome Dynamics and Allostery in Drug Design

PubMed Central

Osmulski, Pawel A.

2014-01-01

Abstract Significance: The proteasome is the essential protease that is responsible for regulated cleavage of the bulk of intracellular proteins. Its central role in cellular physiology has been exploited in therapies against aggressive cancers where proteasome-specific competitive inhibitors that block proteasome active centers are very effectively used. However, drugs regulating this essential protease are likely to have broader clinical usefulness. The non-catalytic sites of the proteasome emerge as an attractive alternative target in search of highly specific and diverse proteasome regulators. Recent Advances: Crystallographic models of the proteasome leave the false impression of fixed structures with minimal molecular dynamics lacking long-distance allosteric signaling. However, accumulating biochemical and structural observations strongly support the notion that the proteasome is regulated by precise allosteric interactions arising from protein dynamics, encouraging the active search for allosteric regulators. Here, we discuss properties of several promising compounds that affect substrate gating and processing in antechambers, and interactions of the catalytic core with regulatory proteins. Critical Issues: Given the structural complexity of proteasome assemblies, it is a painstaking process to better understand their allosteric regulation and molecular dynamics. Here, we discuss the challenges and achievements in this field. We place special emphasis on the role of atomic force microscopy imaging in probing the allostery and dynamics of the proteasome, and in dissecting the mechanisms involving small-molecule allosteric regulators. Future Directions: New small-molecule allosteric regulators may become a next generation of drugs targeting the proteasome, which is critical to the development of new therapies in cancers and other diseases. Antioxid. Redox Signal. 21, 2286–2301. PMID:24410482

A comprehensive analysis of 3′ end sequencing data sets reveals novel polyadenylation signals and the repressive role of heterogeneous ribonucleoprotein C on cleavage and polyadenylation

PubMed Central

Gruber, Andreas J.; Schmidt, Ralf; Gruber, Andreas R.; Martin, Georges; Ghosh, Souvik; Belmadani, Manuel; Keller, Walter

2016-01-01

Alternative polyadenylation (APA) is a general mechanism of transcript diversification in mammals, which has been recently linked to proliferative states and cancer. Different 3′ untranslated region (3′ UTR) isoforms interact with different RNA-binding proteins (RBPs), which modify the stability, translation, and subcellular localization of the corresponding transcripts. Although the heterogeneity of pre-mRNA 3′ end processing has been established with high-throughput approaches, the mechanisms that underlie systematic changes in 3′ UTR lengths remain to be characterized. Through a uniform analysis of a large number of 3′ end sequencing data sets, we have uncovered 18 signals, six of which are novel, whose positioning with respect to pre-mRNA cleavage sites indicates a role in pre-mRNA 3′ end processing in both mouse and human. With 3′ end sequencing we have demonstrated that the heterogeneous ribonucleoprotein C (HNRNPC), which binds the poly(U) motif whose frequency also peaks in the vicinity of polyadenylation (poly(A)) sites, has a genome-wide effect on poly(A) site usage. HNRNPC-regulated 3′ UTRs are enriched in ELAV-like RBP 1 (ELAVL1) binding sites and include those of the CD47 gene, which participate in the recently discovered mechanism of 3′ UTR–dependent protein localization (UDPL). Our study thus establishes an up-to-date, high-confidence catalog of 3′ end processing sites and poly(A) signals, and it uncovers an important role of HNRNPC in regulating 3′ end processing. It further suggests that U-rich elements mediate interactions with multiple RBPs that regulate different stages in a transcript's life cycle. PMID:27382025

The protective role of maternal posttraumatic growth and cognitive trauma processing among Palestinian mothers and infants.

PubMed

Diab, Safwat Y; Isosävi, Sanna; Qouta, Samir R; Kuittinen, Saija; Punamäki, Raija-Leena

2018-02-01

War survivors use multiple cognitive and emotional processes to protect their mental health from the negative impacts of trauma. Because mothers and infants may be especially vulnerable to trauma in conditions of war, it is urgent to determine which cognitive and emotional processes are effective for preventing negative trauma impacts." This study examined whether mothers' high posttraumatic growth (PTG) and positive posttraumatic cognitions (PTC) protected (a) their own mental health and (b) their infants' stress regulation and sensorimotor and language development from the effects of war trauma. The participants were 511 Palestinian mothers and their infants living in the Gaza strip. The mothers were interviewed in their second trimester of pregnancy (T1) as well as when the infant was four months (T2) and twelve months (T3). Mothers reported posttraumatic growth (PTG; Tedeschi & Calhoun, 1996) at T1 and posttraumatic cognitions (PTCI; Foa et al., 1999) at T2. They also reported their exposure to traumatic war events both at T1 and T3 and described their mental health conditions (e.g., PTSD and/or depressive and dissociation symptoms) at T3. The Infant Behaviour Questionnaire (IBQ) was used to measure infants' stress regulation at T2 and sensorimotor and language development at T3. The results, based on regression analyses with interaction terms between trauma and PTG, showed that high levels of traumatic war events were not associated with high levels of PTSD, depressive, or dissociation symptoms among mothers showing high levels of PTG. This suggests that PTG may protect maternal mental health from the effects of trauma. In turn, positive maternal PTCs appeared to protect the infants' stress regulation from the effects of war trauma. The study concludes by discussing ways to develop and implement preventive interventions for mother-infant dyads in war conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

The Self-Regulating Brain: Cortical-Subcortical Feedback and the Development of Intelligent Action

ERIC Educational Resources Information Center

Lewis, Marc D.; Todd, Rebecca M.

2007-01-01

To speak of cognitive regulation versus emotion regulation may be misleading. However, some forms of regulation are carried out by executive processes, subject to voluntary control, while others are carried out by "automatic" processes that are far more primitive. Both sets of processes are in constant interaction, and that interaction gives rise…

miR-34a screened by miRNA profiling negatively regulates Wnt/β-catenin signaling pathway in Aflatoxin B1 induced hepatotoxicity

PubMed Central

Zhu, Liye; Gao, Jing; Huang, Kunlun; Luo, Yunbo; Zhang, Boyang; Xu, Wentao

2015-01-01

Aflatoxin-B1 (AFB1), a hepatocarcinogenic mycotoxin, was demonstrated to induce the high rate of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) participate in the regulation of several biological processes in HCC. However, the function of miRNAs in AFB1-induced HCC has received a little attention. Here, we applied Illumina deep sequencing technology for high-throughout profiling of microRNAs in HepG2 cells lines after treatment with AFB1. Analysis of the differential expression profile of miRNAs in two libraries, we identified 9 known miRNAs and 1 novel miRNA which exhibited abnormal expression. KEGG analysis indicated that predicted target genes of differentially expressed miRNAs are involved in cancer-related pathways. Down-regulated of Drosha, DGCR8 and Dicer 1 indicated an impairment of miRNA biogenesis in response to AFB1. miR-34a was up-regulated significantly, down-regulating the expression of Wnt/β-catenin signaling pathway by target gene β-catenin. Anti-miR-34a can significantly relieved the down-regulated β-catenin and its downstream genes, c-myc and Cyclin D1, and the S-phase arrest in cell cycle induced by AFB1 can also be relieved. These results suggested that AFB1 might down-regulate Wnt/β-catenin signaling pathway in HepG2 cells by up-regulating miR-34a, which may involve in the mechanism of liver tumorigenesis. PMID:26567713

Discovery of Intramolecular Signal Transduction Network Based on a New Protein Dynamics Model of Energy Dissipation

PubMed Central

Ma, Cheng-Wei; Xiu, Zhi-Long; Zeng, An-Ping

2012-01-01

A novel approach to reveal intramolecular signal transduction network is proposed in this work. To this end, a new algorithm of network construction is developed, which is based on a new protein dynamics model of energy dissipation. A key feature of this approach is that direction information is specified after inferring protein residue-residue interaction network involved in the process of signal transduction. This enables fundamental analysis of the regulation hierarchy and identification of regulation hubs of the signaling network. A well-studied allosteric enzyme, E. coli aspartokinase III, is used as a model system to demonstrate the new method. Comparison with experimental results shows that the new approach is able to predict all the sites that have been experimentally proved to desensitize allosteric regulation of the enzyme. In addition, the signal transduction network shows a clear preference for specific structural regions, secondary structural types and residue conservation. Occurrence of super-hubs in the network indicates that allosteric regulation tends to gather residues with high connection ability to collectively facilitate the signaling process. Furthermore, a new parameter of propagation coefficient is defined to determine the propagation capability of residues within a signal transduction network. In conclusion, the new approach is useful for fundamental understanding of the process of intramolecular signal transduction and thus has significant impact on rational design of novel allosteric proteins. PMID:22363664

Cell cycle regulation by the intrinsically disordered proteins p21 and p27.

PubMed

Yoon, Mi-Kyung; Mitrea, Diana M; Ou, Li; Kriwacki, Richard W

2012-10-01

Today, it is widely accepted that proteins that lack highly defined globular three-dimensional structures, termed IDPs (intrinsically disordered proteins), play key roles in myriad biological processes. Our understanding of how intrinsic disorder mediates biological function is, however, incomplete. In the present paper, we review disorder-mediated cell cycle regulation by two intrinsically disordered proteins, p21 and p27. A structural adaptation mechanism involving a stretchable dynamic linker helix allows p21 to promiscuously recognize the various Cdk (cyclin-dependent kinase)-cyclin complexes that regulate cell division. Disorder within p27 mediates transmission of an N-terminal tyrosine phosphorylation signal to a C-terminal threonine phosphorylation, constituting a signalling conduit. These mechanisms are mediated by folding upon binding p21/p27's regulatory targets. However, residual disorder within the bound state contributes critically to these functional mechanisms. Our studies provide insights into how intrinsic protein disorder mediates regulatory processes and opportunities for designing drugs that target cancer-associated IDPs.

Impaired JIP3-dependent axonal lysosome transport promotes amyloid plaque pathology

PubMed Central

Gowrishankar, Swetha; Wu, Yumei

2017-01-01

Lysosomes robustly accumulate within axonal swellings at Alzheimer’s disease (AD) amyloid plaques. However, the underlying mechanisms and disease relevance of such lysosome accumulations are not well understood. Motivated by these problems, we identified JNK-interacting protein 3 (JIP3) as an important regulator of axonal lysosome transport and maturation. JIP3 knockout mouse neuron primary cultures accumulate lysosomes within focal axonal swellings that resemble the dystrophic axons at amyloid plaques. These swellings contain high levels of amyloid precursor protein processing enzymes (BACE1 and presenilin 2) and are accompanied by elevated Aβ peptide levels. The in vivo importance of the JIP3-dependent regulation of axonal lysosomes was revealed by the worsening of the amyloid plaque pathology arising from JIP3 haploinsufficiency in a mouse model of AD. These results establish the critical role of JIP3-dependent axonal lysosome transport in regulating amyloidogenic amyloid precursor protein processing and support a model wherein Aβ production is amplified by plaque-induced axonal lysosome transport defects. PMID:28784610

Tumor Suppression and Promotion by Autophagy

PubMed Central

Ávalos, Yenniffer; Canales, Jimena; Criollo, Alfredo; Quest, Andrew F. G.

2014-01-01

Autophagy is a highly regulated catabolic process that involves lysosomal degradation of proteins and organelles, mostly mitochondria, for the maintenance of cellular homeostasis and reduction of metabolic stress. Problems in the execution of this process are linked to different pathological conditions, such as neurodegeneration, aging, and cancer. Many of the proteins that regulate autophagy are either oncogenes or tumor suppressor proteins. Specifically, tumor suppressor genes that negatively regulate mTOR, such as PTEN, AMPK, LKB1, and TSC1/2 stimulate autophagy while, conversely, oncogenes that activate mTOR, such as class I PI3K, Ras, Rheb, and AKT, inhibit autophagy, suggesting that autophagy is a tumor suppressor mechanism. Consistent with this hypothesis, the inhibition of autophagy promotes oxidative stress, genomic instability, and tumorigenesis. Nevertheless, autophagy also functions as a cytoprotective mechanism under stress conditions, including hypoxia and nutrient starvation, that promotes tumor growth and resistance to chemotherapy in established tumors. Here, in this brief review, we will focus the discussion on this ambiguous role of autophagy in the development and progression of cancer. PMID:25328887

Tumor suppression and promotion by autophagy.

PubMed

Ávalos, Yenniffer; Canales, Jimena; Bravo-Sagua, Roberto; Criollo, Alfredo; Lavandero, Sergio; Quest, Andrew F G

2014-01-01

Autophagy is a highly regulated catabolic process that involves lysosomal degradation of proteins and organelles, mostly mitochondria, for the maintenance of cellular homeostasis and reduction of metabolic stress. Problems in the execution of this process are linked to different pathological conditions, such as neurodegeneration, aging, and cancer. Many of the proteins that regulate autophagy are either oncogenes or tumor suppressor proteins. Specifically, tumor suppressor genes that negatively regulate mTOR, such as PTEN, AMPK, LKB1, and TSC1/2 stimulate autophagy while, conversely, oncogenes that activate mTOR, such as class I PI3K, Ras, Rheb, and AKT, inhibit autophagy, suggesting that autophagy is a tumor suppressor mechanism. Consistent with this hypothesis, the inhibition of autophagy promotes oxidative stress, genomic instability, and tumorigenesis. Nevertheless, autophagy also functions as a cytoprotective mechanism under stress conditions, including hypoxia and nutrient starvation, that promotes tumor growth and resistance to chemotherapy in established tumors. Here, in this brief review, we will focus the discussion on this ambiguous role of autophagy in the development and progression of cancer.

Engineered channel controls limiting spawning habitat rehabilitation success on regulated gravel-bed rivers

NASA Astrophysics Data System (ADS)

Brown, Rocko A.; Pasternack, Gregory B.

2008-05-01

In efforts to rehabilitate regulated rivers for ecological benefits, the flow regime has been one of the primary focal points of management strategies. However, channel engineering can impact channel geometry such that hydraulic and geomorphic responses to flow reregulation do not yield the sought for benefits. To illustrate and assess the impacts of structural channel controls and flow reregulation on channel processes and fish habitat quality in multiple life stages, a highly detailed digital elevation model was collected and analyzed for a river reach right below a dam using a suite of hydrologic, hydraulic, geomorphic, and ecological methods. Results showed that, despite flow reregulation to produce a scaled-down natural hydrograph, anthropogenic boundary controls have severely altered geomorphic processes associated with geomorphic self-sustainability and instream habitat availability in the case study. Given the similarity of this stream to many others, we concluded that the potential utility of natural flow regime reinstatement in regulated gravel-bed rivers is conditional on concomitant channel rehabilitation.

Nemo regulates cell dynamics and represses the expression of miple, a midkine/pleiotrophin cytokine, during ommatidial rotation

PubMed Central

Muñoz-Soriano, Verónica; Ruiz, Carlos; Pérez-Alonso, Manuel; Mlodzik, Marek; Paricio, Nuria

2013-01-01

Ommatidial rotation is one of the most important events for correct patterning of the Drosophila eye. Although several signaling pathways are involved in this process, few genes have been shown to specifically affect it. One of them is nemo (nmo), which encodes a MAP-like protein kinase that regulates the rate of rotation throughout the entire process, and serves as a link between core planar cell polarity (PCP) factors and the E-cadherin–β-catenin complex. To determine more precisely the role of nmo in ommatidial rotation, live-imaging analyses in nmo mutant and wild-type early pupal eye discs were performed. We demonstrate that ommatidial rotation is not a continuous process, and that rotating and non-rotating interommatidial cells are very dynamic. Our in vivo analyses also show that nmo regulates the speed of rotation and is required in cone cells for correct ommatidial rotation, and that these cells as well as interommatidial cells are less dynamic in nmo mutants. Furthermore, microarray analyses of nmo and wild-type larval eye discs led us to identify new genes and signaling pathways related to nmo function during this process. One of them, miple, encodes the Drosophila ortholog of the midkine/pleiotrophin secreted cytokines that are involved in cell migration processes. miple is highly up-regulated in nmo mutant discs. Indeed, phenotypic analyses reveal that miple overexpression leads to ommatidial rotation defects. Genetic interaction assays suggest that miple is signaling through Ptp99A, the Drosophila ortholog of the vertebrate midkine/pleiotrophin PTPζ receptor. Accordingly, we propose that one of the roles of Nmo during ommatial rotation is to repress miple expression, which may in turn affect the dynamics in E-cadherin–β-catenin complexes. PMID:23428616

Quantitative Proteomic Profiling of Low-Dose Ionizing Radiation Effects in a Human Skin Model

PubMed Central

Hengel, Shawna M.; Aldrich, Joshua T.; Waters, Katrina M.; Pasa-Tolic, Ljiljana; Stenoien, David L.

2014-01-01

To assess responses to low-dose ionizing radiation (LD-IR) exposures potentially encountered during medical diagnostic procedures, nuclear accidents or terrorist acts, a quantitative proteomic approach was used to identify changes in protein abundance in a reconstituted human skin tissue model treated with 0.1 Gy of ionizing radiation. To improve the dynamic range of the assay, subcellular fractionation was employed to remove highly abundant structural proteins and to provide insight into radiation-induced alterations in protein localization. Relative peptide quantification across cellular fractions, control and irradiated samples was performing using 8-plex iTRAQ labeling followed by online two-dimensional nano-scale liquid chromatography and high resolution MS/MS analysis. A total of 107 proteins were detected with statistically significant radiation-induced change in abundance (>1.5 fold) and/or subcellular localization compared to controls. The top biological pathways identified using bioinformatics include organ development, anatomical structure formation and the regulation of actin cytoskeleton. From the proteomic data, a change in proteolytic processing and subcellular localization of the skin barrier protein, filaggrin, was identified, and the results were confirmed by western blotting. This data indicate post-transcriptional regulation of protein abundance, localization and proteolytic processing playing an important role in regulating radiation response in human tissues. PMID:28250387

How Messenger RNA and Nascent Chain Sequences Regulate Translation Elongation.

PubMed

Choi, Junhong; Grosely, Rosslyn; Prabhakar, Arjun; Lapointe, Christopher P; Wang, Jinfan; Puglisi, Joseph D

2018-06-20

Translation elongation is a highly coordinated, multistep, multifactor process that ensures accurate and efficient addition of amino acids to a growing nascent-peptide chain encoded in the sequence of translated messenger RNA (mRNA). Although translation elongation is heavily regulated by external factors, there is clear evidence that mRNA and nascent-peptide sequences control elongation dynamics, determining both the sequence and structure of synthesized proteins. Advances in methods have driven experiments that revealed the basic mechanisms of elongation as well as the mechanisms of regulation by mRNA and nascent-peptide sequences. In this review, we highlight how mRNA and nascent-peptide elements manipulate the translation machinery to alter the dynamics and pathway of elongation.

Modelling hydrological processes and analysing water-related ecosystem services of Western Siberian lowland basins

NASA Astrophysics Data System (ADS)

Schmalz, Britta; Kiesel, Jens; Kruse, Marion; Pfannerstill, Matthias; Sheludkov, Artyom; Khoroshavin, Vitaliy; Veshkurseva, Tatyana; Müller, Felix; Fohrer, Nicola

2015-04-01

For discussing and planning sustainable land management of river basins, stakeholders need suitable information on spatio-temporal patterns of hydrological components and ecosystem services. The ecosystem services concept, i.e., services provided by ecosystems that contribute to human welfare benefits, contributes comprehensive information for sustainable river management. This study shows an approach to use ecohydrological modelling results for quantifying and assessing water-related ecosystem services in three lowland river basins in Western Siberia, a region which is of global significance in terms of carbon sequestration, agricultural production and biodiversity preservation. Using the ecohydrological model SWAT, the three basins Pyschma (16762 km²), Vagai (3348 km²) and Loktinka (373 km²) were modelled following a gradient from the landscape units taiga, pre-taiga to forest steppe. For a correct representation of the Siberian lowland hydrology, the consideration of snow melt and retention of surface runoff as well as the implementation of a second groundwater aquifer was of great importance. Good to satisfying model performances were obtained for the extreme hydrological conditions. The simulated SWAT output variables of different hydrological processes were used as indicators for the two regulating services water flow and erosion regulation. The model results were translated into a relative ecosystem service valuation scale. The resulting ecosystem service maps show different spatial and seasonal patterns. Although the high resolution modelling results are averaged out within the aggregated relative valuation scale, seasonal differences can be depicted: during snowmelt, low relevant regulation can be determined, especially for water flow regulation, but a very high relevant regulation was calculated for the vegetation period during summer and for the winter period. The SWAT model serves as a suitable quantification method for the assessment of water-related ecosystem services on different spatial scales and ecoregions of the Western Siberian lowlands.

Gonadotropin-dependent regulation of the prostaglandin E2 receptor in equine preovulatory follicles during the ovulatory process in mares.

PubMed

Sayasith, Khampoune; Bouchard, Nadine; Doré, Monique; Sirois, Jean

2009-02-01

The objectives of the study were to clone the primary structure of the prostaglandin E2 receptor subtype 2 (PTGER2) cDNA and to characterize its regulation in equine follicles during gonadotropin-induced ovulation. Results from DNA isolation indicated that the equine PTGER2 cDNA encodes a predicted 353-amino acid protein, which is highly similar (76-85%) to known mammalian homologues. The regulation of PTGER2 was studied by semi-quantitative RT-PCR/Southern blot using preparations of theca interna and mural granulosa cells isolated from equine follicles 0-39 hr post-treatment with human chorionic gonadotropin (hCG). Results indicated that a significant increase of PTGER2 mRNA occurred at 24 and 39 hr post-hCG in granulosa cells, and 30 and 33 hr post-hCG in theca cells (P < 0.05). Immunohistochemical staining and immunoblotting performed on equine follicular samples showed a corresponding increase of PTGER2 protein in both cell types after treatment with hCG. Levels of PTGER2 mRNA were also high in uterus, thymus and spleen, but moderate to low in other tested tissues. In the ovary, the expression of PTGER4 mRNA was observed and predominantly occurred in granulosa cells, with highest abundance of transcripts observed at 12 and 39 hr post-hCG. Thus, this study reports for the first time in mares that the ovulatory process is accompanied by the gonadotropin-dependent up-regulation of PTGER2 and PTGER4, which may in turn regulate PGE2-mediated preovulatory effects. (c) 2008 Wiley-Liss, Inc.

Phosphoproteomics profiling of human skin fibroblast cells reveals pathways and proteins affected by low doses of ionizing radiation

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

Yang, Feng; Waters, Katrina M.; Miller, John H.

2010-11-30

Background: High doses of ionizing radiation result in biological damage, however the precise relationships between long term health effects, including cancer, and low dose exposures remain poorly understood and are currently extrapolated using high dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose dependent responses to radiation. Principle Findings: We have identified 6845 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts one hour post-exposure. Dual statistical analyses based on spectral counts and peakmore » intensities identified 287 phosphopeptides (from 231 proteins) and 244 phosphopeptides (from 182 proteins) that varied significantly following exposure to 2 and 50 cGy respectively. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatics analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role of MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Conlcusions: Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provides a basis for the systems level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low dose radiation exposure on human health.« less

Emotion Regulation Moderates the Association between Empathy and Prosocial Behavior

PubMed Central

Lockwood, Patricia L.; Seara-Cardoso, Ana; Viding, Essi

2014-01-01

Theory and evidence suggest that empathy is an important motivating factor for prosocial behaviour and that emotion regulation, i.e. the capacity to exert control over an emotional response, may moderate the degree to which empathy is associated with prosocial behaviour. However, studies to date have not simultaneously explored the associations between different empathic processes and prosocial behaviour, nor whether different types of emotion regulation strategies (e.g. cognitive reappraisal and expressive suppression) moderate associations between empathy and prosocial behaviour. One hundred–and-ten healthy adults completed questionnaire measures of empathy, emotion regulation and prosocial tendencies. In this sample, both affective and cognitive empathy predicted self-reported prosocial tendencies. In addition, cognitive reappraisal moderated the association between affective empathy and prosocial tendencies. Specifically, there was a significant positive association between empathy and prosocial tendencies for individuals with a low or average tendency to reappraise but not for those with a high tendency to reappraise. Our findings suggest that, in general, empathy is positively associated with prosocial behaviour. However, this association is not significant for individuals with a high tendency for cognitive reappraisal. PMID:24810604

Emotion regulation moderates the association between empathy and prosocial behavior.

PubMed

Lockwood, Patricia L; Seara-Cardoso, Ana; Viding, Essi

2014-01-01

Theory and evidence suggest that empathy is an important motivating factor for prosocial behaviour and that emotion regulation, i.e. the capacity to exert control over an emotional response, may moderate the degree to which empathy is associated with prosocial behaviour. However, studies to date have not simultaneously explored the associations between different empathic processes and prosocial behaviour, nor whether different types of emotion regulation strategies (e.g. cognitive reappraisal and expressive suppression) moderate associations between empathy and prosocial behaviour. One hundred-and-ten healthy adults completed questionnaire measures of empathy, emotion regulation and prosocial tendencies. In this sample, both affective and cognitive empathy predicted self-reported prosocial tendencies. In addition, cognitive reappraisal moderated the association between affective empathy and prosocial tendencies. Specifically, there was a significant positive association between empathy and prosocial tendencies for individuals with a low or average tendency to reappraise but not for those with a high tendency to reappraise. Our findings suggest that, in general, empathy is positively associated with prosocial behaviour. However, this association is not significant for individuals with a high tendency for cognitive reappraisal.

Intrinsic functional connectivity underlying successful emotion regulation of angry faces

PubMed Central

Morawetz, Carmen; Kellermann, Tanja; Kogler, Lydia; Radke, Sina; Blechert, Jens; Derntl, Birgit

2016-01-01

Most of our social interaction is naturally based on emotional information derived from the perception of faces of other people. Negative facial expressions of a counterpart might trigger negative emotions and initiate emotion regulatory efforts to reduce the impact of the received emotional message in a perceiver. Despite the high adaptive value of emotion regulation in social interaction, the neural underpinnings of it are largely unknown. To remedy this, this study investigated individual differences in emotion regulation effectiveness during the reappraisal of angry faces on the underlying functional activity using functional magnetic resonance imaging (fMRI) as well as the underlying functional connectivity using resting-state fMRI. Greater emotion regulation ability was associated with greater functional activity in the ventromedial prefrontal cortex. Furthermore, greater functional coupling between activity in the ventrolateral prefrontal cortex and the amygdala was associated with emotion regulation success. Our findings provide a first link between prefrontal cognitive control and subcortical emotion processing systems during successful emotion regulation in an explicitly social context. PMID:27510495

Spatially Distributed Assimilation of Remotely Sensed Leaf Area Index and Potential Evapotranspiration for Hydrologic Modeling in Wetland Landscapes

EPA Science Inventory

Evapotranspiration (ET), a highly dynamic flux in wetland landscapes, regulates the accuracy of surface/sub-surface runoff simulation in a hydrologic model. However, considerable uncertainty in simulating ET-related processes remains, including our limited ability to incorporate ...

31 CFR 540.316 - Uranium enrichment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Uranium enrichment. 540.316 Section... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY HIGHLY ENRICHED URANIUM (HEU) AGREEMENT ASSETS CONTROL REGULATIONS General Definitions § 540.316 Uranium enrichment. The term uranium enrichment means the process of...

31 CFR 540.316 - Uranium enrichment.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Uranium enrichment. 540.316 Section... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY HIGHLY ENRICHED URANIUM (HEU) AGREEMENT ASSETS CONTROL REGULATIONS General Definitions § 540.316 Uranium enrichment. The term uranium enrichment means the process of...

31 CFR 540.316 - Uranium enrichment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Uranium enrichment. 540.316 Section... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY HIGHLY ENRICHED URANIUM (HEU) AGREEMENT ASSETS CONTROL REGULATIONS General Definitions § 540.316 Uranium enrichment. The term uranium enrichment means the process of...

31 CFR 540.316 - Uranium enrichment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Uranium enrichment. 540.316 Section... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY HIGHLY ENRICHED URANIUM (HEU) AGREEMENT ASSETS CONTROL REGULATIONS General Definitions § 540.316 Uranium enrichment. The term uranium enrichment means the process of...

Larvae of small white butterfly, Pieris rapae, express a novel serotonin receptor

USDA-ARS?s Scientific Manuscript database

The biogenic amine serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter in vertebrates and invertebrates. It acts in regulation and modulation of many physiological and behavioral processes through G protein-coupled receptors. Insects express five 5-HT receptor subtypes that share high simila...

Overexpression of the Arabidopsis thaliana signalling peptide TAXIMIN1 affects lateral organ development.

PubMed

Colling, Janine; Tohge, Takayuki; De Clercq, Rebecca; Brunoud, Geraldine; Vernoux, Teva; Fernie, Alisdair R; Makunga, Nokwanda P; Goossens, Alain; Pauwels, Laurens

2015-08-01

Lateral organ boundary formation is highly regulated by transcription factors and hormones such as auxins and brassinosteroids. However, in contrast to many other developmental processes in plants, no role for signalling peptides in the regulation of this process has been reported yet. The first characterization of the secreted cysteine-rich TAXIMIN (TAX) signalling peptides in Arabidopsis is presented here. TAX1 overexpression resulted in minor alterations in the primary shoot and root metabolome, abnormal fruit morphology, and fusion of the base of cauline leaves to stems forming a decurrent leaf attachment. The phenotypes at the paraclade junction match TAX1 promoter activity in this region and are similar to loss of LATERAL ORGAN FUSION (LOF) transcription factor function. Nevertheless, TAX1 expression was unchanged in lof1lof2 paraclade junctions and, conversely, LOF gene expression was unchanged in TAX1 overexpressing plants, suggesting TAX1 may act independently. This study identifies TAX1 as the first plant signalling peptide influencing lateral organ separation and implicates the existence of a peptide signal cascade regulating this process in Arabidopsis. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Red blood cells as modulators of T cell growth and survival.

PubMed

Arosa, Fernando A; Pereira, Carlos F; Fonseca, Ana M

2004-01-01

T cell homeostasis is largely controlled by a balance between cell death and survival and anomalies in either process account for a number of diseases linked to excessive or faulty T cell growth. Yet, the influence that cells outside the immunological system have on these processes has only recently received attention. Accumulated evidence indicate that homeostasis of the CD4+ and CD8+ T cell pools is highly dynamic and regulated by signals delivered by cells and molecules present in the different internal microenvironments. The major function of red blood cells (RBC) is generally considered to be oxygen and carbon dioxide transport. In recent years, however, RBC have been implicated in the regulation of basic physiological processes, from vascular contraction and platelet aggregation to T cell growth and survival. Regulation of T cell survival by RBC may influence the response of selected subsets of T cells to internal or external stimuli and may help explaining the immunomodulatory activities of red blood cells. By interfering in the balance between death and survival RBC become potential tools that can be manipulated to improve or reverse pathological situations characterized by anomalies in the control of T cell growth.

Midgut transcriptome response to a Cry toxin in the diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae).

PubMed

Lei, Yanyuan; Zhu, Xun; Xie, Wen; Wu, Qingjun; Wang, Shaoli; Guo, Zhaojiang; Xu, Baoyun; Li, Xianchun; Zhou, Xuguo; Zhang, Youjun

2014-01-01

To investigate the response of Plutella xylostella transcriptome in defending against a Bt toxin, high-throughput RNA-sequencing was carried out to examine Cry1Ac-susceptible and -resistant strains. The comparative analysis indentified over 2900 differentially expressed unigenes (DEUs) between these two strains. Gene Ontology analysis placed these unigenes primarily into cell, cell part, organelle, binding, catalytic, cellular process, metabolic process, and response to stimulus categories. Based on pathway analyses, DEUs were enriched in oxidoreductase activity and membrane lipid metabolic processes, and they were also significantly enriched in pathways related to the metabolic and biosynthesis of secondary metabolites. Most of the unigenes involved in the metabolic pathway were up-regulated in resistant strains. Within the ABC transporter pathway, majority of the down-regulated unigenes belong to ABCC2 and ABCC10, respectively, while up-regulated unigenes were mainly categorized as ABCG2. Furthermore, two aminopeptidases, and four cadherins encoding genes were significantly elevated as well. This study provides a transcriptome foundation for the identification and functional characterization of genes involved in the Bt resistance in an agriculturally important insect pest, P. xylostella. © 2013 Elsevier B.V. All rights reserved.

[Hormonal regulation of metabolism in the human body in microgravity and during simulation of its physiological effects].

PubMed

Larina, I M

2003-01-01

The paper presents results of investigations into the effects of space flight and simulation experiments of various length on the hormonal regulation of metabolism in the human body. Microgravity was shown to instigate shifts on different levels of the hormonal regulation and consequent adjustment of metabolism to this new environment. For instance, adaptation occurs on the level of basal secretory activity resulting in altered metabolism and formation of a pool of hormones. Metabolism readaptation to the Earth's gravity is dependent on polymorphic processes in the system of hormonal regulation developing in the course of time. Trends in the hormonal regulation of water-electrolyte metabolism during early adaptation point to inequality of contributions of the antidiuretic hormone, natriuretic peptide, and the renin-angiotensin-aldosterone system. In the ground-based simulations responses of the hormonal regulation of water-electrolyte metabolism differ in intensity and types of hormones involved. Temperature variation can modify reactions of the comosis and volume regulating hormones at the beginning of adaptation. Physical-chemical regulation of calcium homeostasis in microgravity reveals itself by a rapid decline of the calcium-binding ability of blood buffers and, later on, degradation of the relative ability of extraplasmic structures to bind calcium. Qualitative and quantitative changes in the diurnal rhythm of the suprarenal steroidogenesis are indicative of modification of intensity of reactions of the main biosynthetic sequences. Countermeasures used by test-subjects in these investigations loosened significantly the aldosterone-secreting biosynthetic sequences but were favorable to the synthesis of testosterone and hydrocortisone. Some of the highly variable processes of hormonal regulation were mute to the diurnal rhythms in the pre-flight and preexperimental periods.

The interplay between the anticipation and subsequent online processing of emotional stimuli as measured by pupillary dilatation: the role of cognitive reappraisal.

PubMed

Vanderhasselt, Marie-Anne; Remue, Jonathan; Ng, Kwun Kei; De Raedt, Rudi

2014-01-01

Emotions can occur during an emotion-eliciting event, but they can also arise when anticipating the event. We used pupillary responses, as a measure of effortful cognitive processing, to test whether the anticipation of an emotional stimulus (positive and negative) influences the subsequent online processing of that emotional stimulus. Moreover, we tested whether individual differences in the habitual use of emotion regulation strategies are associated with pupillary responses during the anticipation and/or online processing of this emotional stimulus. Our results show that, both for positive and negative stimuli, pupillary diameter during the anticipation of emotion-eliciting events is inversely and strongly correlated to pupillary responses during the emotional image presentation. The variance in this temporal interplay between anticipation and online processing was related to individual differences in emotion regulation. Specifically, the results show that high reappraisal scores are related to larger pupil diameter during the anticipation which is related to smaller pupillary responses during the online processing of emotion-eliciting events. The habitual use of expressive suppression was not associated to pupillary responses in the anticipation and subsequent online processing of emotional stimuli. Taken together, the current data suggest (most strongly for individuals scoring high on the habitual use of reappraisal) that larger pupillary responses during the anticipation of an emotional stimulus are indicative of a sustained attentional set activation to prepare for an upcoming emotional stimulus, which subsequently directs a reduced need to cognitively process that emotional event. Hence, because the habitual use of reappraisal is known to have a positive influence on emotional well-being, the interplay between anticipation and online processing of emotional stimuli might be a significant marker of this well-being.

Does Documenting the Regulation Process on a Blog Enhance Pre-Service Teachers' Self- and Co-Regulation in a Collaborative Project?

ERIC Educational Resources Information Center

Cho, Moon-Heum; Lim, Seongmi; Lee, Kyeonghwa

2017-01-01

Students often complain about unsatisfactory experiences resulting from disproportionate contributions to collaborative projects. To improve the experience, we applied regulation theory to design a process to document regulation on a blog and examined whether such documentation enhanced students' self-regulation and co-regulation skills while…

Algorithm of dynamic regulation of a system of duct, for a high accuracy climatic system

NASA Astrophysics Data System (ADS)

Arbatskiy, A. A.; Afonina, G. N.; Glazov, V. S.

2017-11-01

Currently, major part of climatic system, are stationary in projected mode only. At the same time, many modern industrial sites, require constant or periodical changes in technological process. That is 80% of the time, the industrial site is not require ventilation system in projected mode and high precision of climatic parameters must maintain. While that not constantly is in use for climatic systems, which use in parallel for different rooms, we will be have a problem for balance of duct system. For this problem, was created the algorithm for quantity regulation, with minimal changes. Dynamic duct system: Developed of parallel control system of air balance, with high precision of climatic parameters. The Algorithm provide a permanent pressure in main duct, in different a flow of air. Therefore, the ending devises air flow have only one parameter for regulation - flaps open area. Precision of regulation increase and the climatic system provide high precision for temperature and humidity (0,5C for temperature, 5% for relative humidity). Result: The research has been made in CFD-system - PHOENICS. Results for velocity of air in duct, for pressure of air in duct for different operation mode, has been obtained. Equation for air valves positions, with different parameters for climate in room’s, has been obtained. Energy saving potential for dynamic duct system, for different types of a rooms, has been calculated.

The Prospective Joint Effects of Self-Regulation and Impulsive Processes on Early Adolescence Alcohol Use

PubMed Central

O’Connor, Roisin M.; Colder, Craig R.

2015-01-01

Objective: Dual-process models propose that behavior is influenced by the interactive effect of impulsive (automatic) and selfregulatory (controlled) processes. Elaborations of this model posit that the effect of impulsive processes on alcohol use is influenced by capacity and motivation to self-regulate. The interactive effect of these three processes on drinking has not previously been tested. The goal of this study was to provide a developmental extension of this model to early adolescent alcohol use and to test the three-way interaction between impulsive processes (implicit alcohol cognition), self-regulatory capacity (inhibitory and activation control), and self-regulatory motivation (negative alcohol outcome expectancies [AOE]) in a 1-year prospective prediction of adolescent alcohol use. Method: Adolescents (N = 325; 54% girls, mean age = 13.6 years at baseline) completed the Single Category Implicit Association Test and self-reports of alcohol expectancies and use. Inhibitory and activation control were based on parental report. Results: Negative AOE and inhibitory/activation control were supported as moderators of the effect of implicit alcohol cognition on 1-year prospective alcohol use. As expected, weak implicit negative alcohol cognition was associated with elevated alcohol use when both negative AOE and inhibitory control were low. Contrary to hypothesis, when activation control was high, weak implicit negative alcohol cognition was unrelated to alcohol use if negative AOE were high (p = .72) (vs. low, p < .01).Activation control may reflect the ability to plan ahead and act pro-socially. Conclusions: Our study supports current theory suggesting alcohol use is influenced by a complex interplay of impulsive and self-regulatory processes. PMID:26562596

The role of emotion and emotion regulation in social anxiety disorder.

PubMed

Jazaieri, Hooria; Morrison, Amanda S; Goldin, Philippe R; Gross, James J

2015-01-01

Many psychiatric disorders involve problematic patterns of emotional reactivity and regulation. In this review, we consider recent findings regarding emotion and emotion regulation in the context of social anxiety disorder (SAD). We first describe key features of SAD which suggest altered emotional and self-related processing difficulties. Next, we lay the conceptual foundation for a discussion of emotion and emotion regulation and present a common framework for understanding emotion regulation, the process model of emotion regulation. Using the process model, we evaluate the recent empirical literature spanning self-report, observational, behavioral, and physiological methods across five specific families of emotion regulation processes-situation selection, situation modification, attentional deployment, cognitive change, and response modulation. Next, we examine the empirical evidence behind two psychosocial interventions for SAD: cognitive behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR). Throughout, we present suggestions for future directions in the continued examination of emotion and emotion regulation in SAD.

The roles of the amygdala in the affective regulation of body, brain, and behaviour

NASA Astrophysics Data System (ADS)

Mirolli, Marco; Mannella, Francesco; Baldassarre, Gianluca

2010-09-01

Despite the great amount of knowledge produced by the neuroscientific literature on affective phenomena, current models tackling non-cognitive aspects of behaviour are often bio-inspired but rarely bio-constrained. This paper presents a theoretical account of affective systems centred on the amygdala (Amg). This account aims to furnish a general framework and specific pathways to implement models that are more closely related to biological evidence. The Amg, which receives input from brain areas encoding internal states, innately relevant stimuli, and innately neutral stimuli, plays a fundamental role in the motivational and emotional processes of organisms. This role is based on the fact that Amg implements the two associative processes at the core of Pavlovian learning (conditioned stimulus (CS)-unconditioned stimulus (US) and CS-unconditioned response (UR) associations), and that it has the capacity of modulating these associations on the basis of internal states. These functionalities allow the Amg to play an important role in the regulation of the three fundamental classes of affective responses (namely, the regulation of body states, the regulation of brain states via neuromodulators, and the triggering of a number of basic behaviours fundamental for adaptation) and in the regulation of three high-level cognitive processes (namely, the affective labelling of memories, the production of goal-directed behaviours, and the performance of planning and complex decision-making). Our analysis is conducted within a methodological approach that stresses the importance of understanding the brain within an evolutionary/adaptive framework and with the aim of isolating general principles that can potentially account for the wider possible empirical evidence in a coherent fashion.

Long Non-coding RNAs (LncRNA) Regulated by Transforming Growth Factor (TGF) β

PubMed Central

Richards, Edward J.; Zhang, Gu; Li, Zhu-Peng; Permuth-Wey, Jennifer; Challa, Sridevi; Li, Yajuan; Kong, William; Dan, Su; Bui, Marilyn M.; Coppola, Domenico; Mao, Wei-Min; Sellers, Thomas A.; Cheng, Jin Q.

2015-01-01

Long noncoding RNAs (lncRNAs) are emerging as key regulators in various biological processes. Epithelial-to-mesenchymal transition (EMT) is a developmental process hijacked by tumor cells to depart from the primary tumor site, invade surrounding tissue, and establish distant metastases. Transforming growth factor β (TGFβ) signaling has been shown to be a major inducer of EMT and to facilitate breast cancer metastasis. However, the role of lncRNAs in this process remains largely unknown. Here we report a genome-wide lncRNA profile in mouse mammary epithelial NMuMG cells upon TGFβ induction of EMT. Among 10,802 lncRNAs profiled, over 600 were up-regulated and down-regulated during the EMT, respectively. Furthermore, we identify that lncRNA-HIT (HOXA transcript induced by TGFβ) mediates TGFβ function, i.e. depletion of lncRNA-HIT inhibits TGFβ-induced migration, invasion, and EMT in NMuMG. LncRNA-HIT is also significantly elevated in the highly metastatic 4T1 cells. Knockdown of lncRNA-HIT in 4T1 results in decrease of cell migration, invasion, tumor growth, and metastasis. E-cadherin was identified as a major target of lncRNA-HIT. Moreover, lncRNA-HIT is conserved in humans and elevated expression associates with more invasive human primary breast carcinoma. Collectively, these data suggest that a subset of lncRNAs such as lncRNA-HIT play a significant role in regulation of EMT and breast cancer invasion and metastasis, and could be potential therapeutic targets in breast cancers. PMID:25605728

Proteolytic regulation of metabolic enzymes by E3 ubiquitin ligase complexes: lessons from yeast.

PubMed

Nakatsukasa, Kunio; Okumura, Fumihiko; Kamura, Takumi

2015-01-01

Eukaryotic organisms use diverse mechanisms to control metabolic rates in response to changes in the internal and/or external environment. Fine metabolic control is a highly responsive, energy-saving process that is mediated by allosteric inhibition/activation and/or reversible modification of preexisting metabolic enzymes. In contrast, coarse metabolic control is a relatively long-term and expensive process that involves modulating the level of metabolic enzymes. Coarse metabolic control can be achieved through the degradation of metabolic enzymes by the ubiquitin-proteasome system (UPS), in which substrates are specifically ubiquitinated by an E3 ubiquitin ligase and targeted for proteasomal degradation. Here, we review select multi-protein E3 ligase complexes that directly regulate metabolic enzymes in Saccharomyces cerevisiae. The first part of the review focuses on the endoplasmic reticulum (ER) membrane-associated Hrd1 and Doa10 E3 ligase complexes. In addition to their primary roles in the ER-associated degradation pathway that eliminates misfolded proteins, recent quantitative proteomic analyses identified native substrates of Hrd1 and Doa10 in the sterol synthesis pathway. The second part focuses on the SCF (Skp1-Cul1-F-box protein) complex, an abundant prototypical multi-protein E3 ligase complex. While the best-known roles of the SCF complex are in the regulation of the cell cycle and transcription, accumulating evidence indicates that the SCF complex also modulates carbon metabolism pathways. The increasing number of metabolic enzymes whose stability is directly regulated by the UPS underscores the importance of the proteolytic regulation of metabolic processes for the acclimation of cells to environmental changes.

Hypoxia inducible factor-1α regulates autophagy via the p27-E2F1 signaling pathway

PubMed Central

Wang, Pan; Long, Meijing; Zhang, Shijie; Cheng, Zhenyun; Zhao, Xin; He, Fucheng; Liu, Hongchun; Ming, Liang

2017-01-01

Autophagy is a highly conserved process by which the cell contents are delivered to lysosomes for degradation, or are used to provide macromolecules for energy generation under conditions of nutritional starvation. It has previously been demonstrated that cancer cells in hypoxic regions, with an oxygen concentration below the normal physiological level, express hypoxia inducible factor (HIF)-1α, in order to adapt and survive. HIF-1α is important in the regulation of oxygen homeostasis and the transcription of hundreds of genes in response to conditions of hypoxia, hence maintaining energy and redox homeostasis. To determine if HIF-1α modulates autophagy and the underlying molecular mechanisms regulating this process, the human esophageal cancer EC109 and IMR90 human diploid fibroblast cell lines were exposed to normoxic or hypoxic conditions and the expression levels of various proteins subsequently examined. Small interfering RNA was used to silence p27, in order to investigate its role in the process of HIF-1α regulated autophagy. Hypoxia induced autophagy in IMR90 cells and it was revealed that immature IMR90 cells demonstrated an increased rate of autophagy compared with mature cells. HIF-1α promoted EC109 cell autophagy via positively modulating p27, whereas silencing of p27 abolished the autophagy induced by hypoxia. The present study identified the primary components of the p27-E2F1 signaling pathway by which HIF-1α regulates autophagy. A previously unidentified mechanism is here presented, via which cancer cells may generate energy, or obtain macromolecules for survival. PMID:28627618

Exercise-driven metabolic pathways in healthy cartilage.

PubMed

Blazek, A D; Nam, J; Gupta, R; Pradhan, M; Perera, P; Weisleder, N L; Hewett, T E; Chaudhari, A M; Lee, B S; Leblebicioglu, B; Butterfield, T A; Agarwal, S

2016-07-01

Exercise is vital for maintaining cartilage integrity in healthy joints. Here we examined the exercise-driven transcriptional regulation of genes in healthy rat articular cartilage to dissect the metabolic pathways responsible for the potential benefits of exercise. Transcriptome-wide gene expression in the articular cartilage of healthy Sprague-Dawley female rats exercised daily (low intensity treadmill walking) for 2, 5, or 15 days was compared to that of non-exercised rats, using Affymetrix GeneChip arrays. Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO)-term enrichment and Functional Annotation analysis of differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genome (KEGG) pathway mapper was used to identify the metabolic pathways regulated by exercise. Microarray analysis revealed that exercise-induced 644 DEGs in healthy articular cartilage. The DAVID bioinformatics tool demonstrated high prevalence of functional annotation clusters with greater enrichment scores and GO-terms associated with extracellular matrix (ECM) biosynthesis/remodeling and inflammation/immune response. The KEGG database revealed that exercise regulates 147 metabolic pathways representing molecular interaction networks for Metabolism, Genetic Information Processing, Environmental Information Processing, Cellular Processes, Organismal Systems, and Diseases. These pathways collectively supported the complex regulation of the beneficial effects of exercise on the cartilage. Overall, the findings highlight that exercise is a robust transcriptional regulator of a wide array of metabolic pathways in healthy cartilage. The major actions of exercise involve ECM biosynthesis/cartilage strengthening and attenuation of inflammatory pathways to provide prophylaxis against onset of arthritic diseases in healthy cartilage. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Anaerobic digestion of municipal solid wastes containing variable proportions of waste types.

PubMed

Akunna, J C; Abdullahi, Y A; Stewart, N A

2007-01-01

In many parts of the world there are significant seasonal variations in the production of the main organic wastes, food and green wastes. These waste types display significant differences in their biodegradation rates. This study investigated the options for ensuring process stability during the start up and operation of thermophilic high-solids anaerobic digestion of feedstock composed of varying proportions of food and green wastes. The results show that high seed sludge to feedstock ratio (or low waste loading rate) is necessary for ensuring process pH stability without chemical addition. It was also found that the proportion of green wastes in the feedstock can be used to regulate process pH, particularly when operating at high waste loading rates (or low seed sludge to feedstock ratios). The need for chemical pH correction during start-up and digestion operation decreased with increase in green wastes content of the feedstock. Food wastes were found to be more readily biodegradable leading to higher solids reduction while green wastes brought about pH stability and higher digestate solid content. Combining both waste types in various proportions brought about feedstock with varying buffering capacity and digestion performance. Thus, careful selection of feedstock composition can minimise the need for chemical pH regulation as well as reducing the cost for digestate dewatering for final disposal.

MOS1 Osmosensor of Metarhizium anisopliae Is Required for Adaptation to Insect Host Hemolymph▿

PubMed Central

Wang, Chengshu; Duan, Zhibing; St. Leger, Raymond J.

2008-01-01

Entomopathogenic fungi such as Metarhizium anisopliae infect insects by direct penetration of the cuticle, after which the fungus adapts to the high osmotic pressure of the hemolymph and multiplies. Here we characterize the M. anisopliae Mos1 gene and demonstrate that it encodes the osmosensor required for this process. MOS1 contains transmembrane regions and a C-terminal Src homology 3 domain similar to those of yeast osmotic adaptor proteins, and homologs of MOS1 are widely distributed in the fungal kingdom. Reverse transcription-PCR demonstrated that Mos1 is up-regulated in insect hemolymph as well as artificial media with high osmotic pressure. Transformants containing an antisense vector directed to the Mos1 mRNA depleted transcript levels by 80%. This produced selective alterations in regulation of genes involved in hyphal body formation, cell membrane stiffness, and generation of intracellular turgor pressure, suggesting that these processes are mediated by MOS1. Consistent with a role in stress responses, transcript depletion of Mos1 increased sensitivity to osmotic and oxidative stresses and to compounds that interfere with cell wall biosynthesis. It also disrupted developmental processes, including formation of appressoria and hyphal bodies. Insect bioassays confirmed that Mos1 knockdown significantly reduces virulence. Overall, our data show that M. anisopliae MOS1 mediates cellular responses to high osmotic pressure and subsequent adaptations to colonize host hemolymph. PMID:18055914

MicroRNA modulation of lipid metabolism and oxidative stress in cardiometabolic diseases.

PubMed

Aranda, Juan F; Madrigal-Matute, Julio; Rotllan, Noemi; Fernández-Hernando, Carlos

2013-09-01

The regulation of the metabolism of cholesterol has been one of the most studied biological processes since its first isolation from gallstones in 1784. High levels of plasma low-density lipoprotein (LDL) cholesterol and reduced levels of plasma high-density lipoprotein (HDL) cholesterol are widely recognized as major risk factors of cardiovascular disease. An imbalance in the production of reactive oxygen species can oxidize LDL particles, increasing the levels of the highly proatherogenic oxidized LDL. Furthermore, under pathological scenarios, numerous molecules can function as pro-oxidants, such as iron or (high levels of) glucose. In addition to the classical mechanisms regulating lipid homeostasis, recent studies have demonstrated the important role of microRNAs (miRNAs) as regulators of lipoprotein metabolism, oxidative derivatives of lipoprotein, and redox balance. Here, we summarize recent findings in the field, highlighting the contributions of some miRNAs to lipid- and oxidative-associated pathologies. We also discuss how therapeutic intervention of miRNAs may be a promising strategy to decrease LDL, increase HDL, and ameliorate lipid- and oxidative-related disorders, including atherosclerosis, nonalcoholic fatty liver disease, and metabolic syndrome. © 2013 Elsevier Inc. All rights reserved.

Engineering of Machine tool’s High-precision electric drives

NASA Astrophysics Data System (ADS)

Khayatov, E. S.; Korzhavin, M. E.; Naumovich, N. I.

2018-03-01

In the article it is shown that in mechanisms with numerical program control, high quality of processes can be achieved only in systems that provide adjustment of the working element’s position with high accuracy, and this requires an expansion of the regulation range by the torque. In particular, the use of synchronous reactive machines with independent excitation control makes it possible to substantially increase the moment overload in the sequential excitation circuit. Using mathematical and physical modeling methods, it is shown that in the electric drive with a synchronous reactive machine with independent excitation in a circuit with sequential excitation, it is possible to significantly expand the range of regulation by the torque and this is achieved by the effect of sequential excitation, which makes it possible to compensate for the transverse reaction of the armature.

High voltage systems (tube-type microwave)/low voltage system (solid-state microwave) power distribution

NASA Technical Reports Server (NTRS)

Nussberger, A. A.; Woodcock, G. R.

1980-01-01

SPS satellite power distribution systems are described. The reference Satellite Power System (SPS) concept utilizes high-voltage klystrons to convert the onboard satellite power from dc to RF for transmission to the ground receiving station. The solar array generates this required high voltage and the power is delivered to the klystrons through a power distribution subsystem. An array switching of solar cell submodules is used to maintain bus voltage regulation. Individual klystron dc voltage conversion is performed by centralized converters. The on-board data processing system performs the necessary switching of submodules to maintain voltage regulation. Electrical power output from the solar panels is fed via switch gears into feeder buses and then into main distribution buses to the antenna. Power also is distributed to batteries so that critical functions can be provided through solar eclipses.

Using Self-regulation to Successfully Overcome the Negotiation Disadvantage of Low Power

PubMed Central

Jäger, Andreas; Loschelder, David D.; Friese, Malte

2017-01-01

A plethora of studies has demonstrated that low-power negotiators attain lower outcomes compared to high-power negotiators. We argue that this low-power disadvantage can be conceptualized as impaired goal attainment and that self-regulation can help to overcome it. Three experiments tested this assertion. In Study 1, low-power negotiators attained lower profits compared to their high-power opponents in a face-to-face negotiation. Negotiators who set themselves goals and those who additionally formed if-then plans prior to the negotiation overcame the low-power disadvantage. Studies 2 and 3 replicated these effects in computer-mediated negotiations: Low-power negotiators conceded more than high-power negotiators. Again, setting goals and forming additional if-then plans helped to counter the power disadvantage. Process analyses revealed that negotiators’ concession-making at the start of the negotiation mediated both the low-power disadvantage and the beneficial effects of self-regulation. The present findings show how the low-power disadvantage unfolds in negotiations and how self-regulatory techniques can help to overcome it. PMID:28382005

Using Self-regulation to Successfully Overcome the Negotiation Disadvantage of Low Power.

PubMed

Jäger, Andreas; Loschelder, David D; Friese, Malte

2017-01-01

A plethora of studies has demonstrated that low-power negotiators attain lower outcomes compared to high-power negotiators. We argue that this low-power disadvantage can be conceptualized as impaired goal attainment and that self-regulation can help to overcome it. Three experiments tested this assertion. In Study 1, low-power negotiators attained lower profits compared to their high-power opponents in a face-to-face negotiation. Negotiators who set themselves goals and those who additionally formed if-then plans prior to the negotiation overcame the low-power disadvantage. Studies 2 and 3 replicated these effects in computer-mediated negotiations: Low-power negotiators conceded more than high-power negotiators. Again, setting goals and forming additional if-then plans helped to counter the power disadvantage. Process analyses revealed that negotiators' concession-making at the start of the negotiation mediated both the low-power disadvantage and the beneficial effects of self-regulation. The present findings show how the low-power disadvantage unfolds in negotiations and how self-regulatory techniques can help to overcome it.

Reverse Engineering of Genome-wide Gene Regulatory Networks from Gene Expression Data

PubMed Central

Liu, Zhi-Ping

2015-01-01

Transcriptional regulation plays vital roles in many fundamental biological processes. Reverse engineering of genome-wide regulatory networks from high-throughput transcriptomic data provides a promising way to characterize the global scenario of regulatory relationships between regulators and their targets. In this review, we summarize and categorize the main frameworks and methods currently available for inferring transcriptional regulatory networks from microarray gene expression profiling data. We overview each of strategies and introduce representative methods respectively. Their assumptions, advantages, shortcomings, and possible improvements and extensions are also clarified and commented. PMID:25937810

Auxin-BR Interaction Regulates Plant Growth and Development

PubMed Central

Tian, Huiyu; Lv, Bingsheng; Ding, Tingting; Bai, Mingyi; Ding, Zhaojun

2018-01-01

Plants develop a high flexibility to alter growth, development, and metabolism to adapt to the ever-changing environments. Multiple signaling pathways are involved in these processes and the molecular pathways to transduce various developmental signals are not linear but are interconnected by a complex network and even feedback mutually to achieve the final outcome. This review will focus on two important plant hormones, auxin and brassinosteroid (BR), based on the most recent progresses about these two hormone regulated plant growth and development in Arabidopsis, and highlight the cross-talks between these two phytohormones. PMID:29403511

The molecular mechanisms underlying lens fiber elongation

PubMed Central

Audette, Dylan S.; Scheiblin, David A.; Duncan, Melinda K.

2016-01-01

Lens fiber cells are highly elongated cells with complex membrane morphologies that are critical for the transparency of the ocular lens. Investigations into the molecular mechanisms underlying lens fiber cell elongation were first reported in the 1960s, however, our understanding of the process is still poor nearly 50 years later. This review summarizes what is currently hypothesized about the regulation of lens fiber cell elongation along with the available experimental evidence, and how this information relates to what is known about the regulation of cell shape/elongation in other cell types, particularly neurons. PMID:27015931

Nuclear Phosphatidylinositol-Phosphate Type I Kinase α-Coupled Star-PAP Polyadenylation Regulates Cell Invasion

PubMed Central

A.P., Sudheesh

2017-01-01

ABSTRACT Star-PAP, a nuclear phosphatidylinositol (PI) signal-regulated poly(A) polymerase (PAP), couples with type I PI phosphate kinase α (PIPKIα) and controls gene expression. We show that Star-PAP and PIPKIα together regulate 3′-end processing and expression of pre-mRNAs encoding key anti-invasive factors (KISS1R, CDH1, NME1, CDH13, FEZ1, and WIF1) in breast cancer. Consistently, the endogenous Star-PAP level is negatively correlated with the cellular invasiveness of breast cancer cells. While silencing Star-PAP or PIPKIα increases cellular invasiveness in low-invasiveness MCF7 cells, Star-PAP overexpression decreases invasiveness in highly invasive MDA-MB-231 cells in a cellular Star-PAP level-dependent manner. However, expression of the PIPKIα-noninteracting Star-PAP mutant or the phosphodeficient Star-PAP (S6A mutant) has no effect on cellular invasiveness. These results strongly indicate that PIPKIα interaction and Star-PAP S6 phosphorylation are required for Star-PAP-mediated regulation of cancer cell invasion and give specificity to target anti-invasive gene expression. Our study establishes Star-PAP–PIPKIα-mediated 3′-end processing as a key anti-invasive mechanism in breast cancer. PMID:29203642

Nuclear Phosphatidylinositol-Phosphate Type I Kinase α-Coupled Star-PAP Polyadenylation Regulates Cell Invasion.

PubMed

A P, Sudheesh; Laishram, Rakesh S

2018-03-01

Star-PAP, a nuclear phosphatidylinositol (PI) signal-regulated poly(A) polymerase (PAP), couples with type I PI phosphate kinase α (PIPKIα) and controls gene expression. We show that Star-PAP and PIPKIα together regulate 3'-end processing and expression of pre-mRNAs encoding key anti-invasive factors ( KISS1R , CDH1 , NME1 , CDH13 , FEZ1 , and WIF1 ) in breast cancer. Consistently, the endogenous Star-PAP level is negatively correlated with the cellular invasiveness of breast cancer cells. While silencing Star-PAP or PIPKIα increases cellular invasiveness in low-invasiveness MCF7 cells, Star-PAP overexpression decreases invasiveness in highly invasive MDA-MB-231 cells in a cellular Star-PAP level-dependent manner. However, expression of the PIPKIα-noninteracting Star-PAP mutant or the phosphodeficient Star-PAP (S6A mutant) has no effect on cellular invasiveness. These results strongly indicate that PIPKIα interaction and Star-PAP S6 phosphorylation are required for Star-PAP-mediated regulation of cancer cell invasion and give specificity to target anti-invasive gene expression. Our study establishes Star-PAP-PIPKIα-mediated 3'-end processing as a key anti-invasive mechanism in breast cancer. Copyright © 2018 A.P. and Laishram.

Melatonin Inhibits Embryonic Salivary Gland Branching Morphogenesis by Regulating Both Epithelial Cell Adhesion and Morphology

PubMed Central

Miura, Jiro; Sakai, Manabu; Uchida, Hitoshi; Nakamura, Wataru; Nohara, Kanji; Maruyama, Yusuke; Hattori, Atsuhiko; Sakai, Takayoshi

2015-01-01

Many organs, including salivary glands, lung, and kidney, are formed by epithelial branching during embryonic development. Branching morphogenesis occurs via either local outgrowths or the formation of clefts that subdivide epithelia into buds. This process is promoted by various factors, but the mechanism of branching morphogenesis is not fully understood. Here we have defined melatonin as a potential negative regulator or “brake” of branching morphogenesis, shown that the levels of it and its receptors decline when branching morphogenesis begins, and identified the process that it regulates. Melatonin has various physiological functions, including circadian rhythm regulation, free-radical scavenging, and gonadal development. Furthermore, melatonin is present in saliva and may have an important physiological role in the oral cavity. In this study, we found that the melatonin receptor is highly expressed on the acinar epithelium of the embryonic submandibular gland. We also found that exogenous melatonin reduces salivary gland size and inhibits branching morphogenesis. We suggest that this inhibition does not depend on changes in either proliferation or apoptosis, but rather relates to changes in epithelial cell adhesion and morphology. In summary, we have demonstrated a novel function of melatonin in organ formation during embryonic development. PMID:25876057

Resilience as Regulation of Developmental and Family Processes

PubMed Central

MacPhee, David; Lunkenheimer, Erika; Riggs, Nathaniel

2015-01-01

Resilience can be defined as establishing equilibrium subsequent to disturbances to a system caused by significant adversity. When families experience adversity or transitions, multiple regulatory processes may be involved in establishing equilibrium, including adaptability, regulation of negative affect, and effective problem-solving skills. The authors’ resilience-as-regulation perspective integrates insights about the regulation of individual development with processes that regulate family systems. This middle-range theory of family resilience focuses on regulatory processes across levels that are involved in adaptation: whole-family systems such as routines and sense of coherence; coregulation of dyads involving emotion regulation, structuring, and reciprocal influences between social partners; and individual self-regulation. Insights about resilience-as-regulation are then applied to family-strengthening interventions that are designed to promote adaptation to adversity. Unresolved issues are discussed in relation to resilience-as-regulation in families, in particular how risk exposure is assessed, interrelations among family regulatory mechanisms, and how families scaffold the development of children’s resilience. PMID:26568647

The cost of empathy: Parent-adolescent conflict predicts emotion dysregulation for highly empathic youth.

PubMed

Van Lissa, Caspar J; Hawk, Skyler T; Koot, Hans M; Branje, Susan; Meeus, Wim H J

2017-09-01

Empathy plays a key role in maintaining close relationships and promoting prosocial conflict resolution. However, research has not addressed the potential emotional cost of adolescents' high empathy, particularly when relationships are characterized by more frequent conflict. The present 6-year longitudinal study (N = 467) investigated whether conflict with parents predicted emotion dysregulation more strongly for high-empathy adolescents than for lower-empathy adolescents. Emotion dysregulation was operationalized at both the experiential level, using mood diary data collected for 3 weeks each year, and at the dispositional level, using annual self-report measures. In line with predictions, we found that more frequent adolescent-parent conflict predicted greater day-to-day mood variability and dispositional difficulties in emotion regulation for high-empathy adolescents, but not for average- and low-empathy adolescents. Mood variability and difficulties in emotion regulation, in turn, also predicted increased conflict with parents. These links were not moderated by empathy. Moreover, our research allowed for a novel investigation of the interplay between experiential and dispositional emotion dysregulation. Day-to-day mood variability predicted increasing dispositional difficulties in emotion regulation over time, which suggests that experiential dysregulation becomes consolidated into dispositional difficulties in emotion regulation. Moderated mediation analyses revealed that, for high-empathy adolescents, conflict was a driver of this dysregulation consolidation process. Finally, emotion dysregulation played a role in overtime conflict maintenance for high-empathy adolescents. This suggests that, through emotion dysregulation, high empathy may paradoxically also contribute to maintaining negative adolescent-parent interactions. Our research indicates that high empathy comes at a cost when adolescent-parent relationships are characterized by greater negativity. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Geomorphic response to flow regulation and channel and floodplain alteration in the gravel-bedded Cedar River, Washington, USA

USGS Publications Warehouse

Gendaszek, Andrew S.; Magirl, Christopher S.; Czuba, Christiana R.

2012-01-01

Decadal- to annual-scale analyses of changes to the fluvial form and processes of the Cedar River in Washington State, USA, reveal the effects of flow regulation, bank stabilization, and log-jam removal on a gravel-bedded river in a temperate climate. During the twentieth century, revetments were built along ~ 60% of the lower Cedar River's length and the 2-year return period flow decreased by 47% following flow regulation beginning in 1914. The formerly wide, anastomosing channel narrowed by over 50% from an average of 47 m in 1936 to 23 m in 1989 and became progressively single threaded. Subsequent high flows and localized revetment removal contributed to an increase in mean channel width to about 34 m by 2011. Channel migration rates between 1936 and 2011 were up to 8 m/year in reaches not confined by revetments or valley walls and less than analysis uncertainty throughout most of the Cedar River's length where bank armoring restricted channel movement. In unconfined reaches where large wood and sediment can be recruited, contemporary high flows, though smaller in magnitude than preregulation high flows, form and maintain geomorphic features such as pools, gravel bars, and side channels. Reaches confined by revetments remain mostly unmodified in the regulated flow regime. While high flows are important for maintaining channel dynamics in the Cedar River, their effectiveness is currently reduced by revetments, limited sediment supply, the lack of large wood available for recruitment to the channel, and decreased magnitude since flow regulation.

Secretomic Insight into Glucose Metabolism of Aspergillus brasiliensis in Solid-State Fermentation.

PubMed

Volke-Sepulveda, Tania; Salgado-Bautista, Daniel; Bergmann, Carl; Wells, Lance; Gutierrez-Sanchez, Gerardo; Favela-Torres, Ernesto

2016-10-07

The genus Aspergillus is ubiquitous in nature and includes various species extensively exploited industrially due to their ability to produce and secrete a variety of enzymes and metabolites. Most processes are performed in submerged fermentation (SmF); however, solid-state fermentation (SSF) offers several advantages, including lower catabolite repression and substrate inhibition and higher productivity and stability of the enzymes produced. This study aimed to explain the improved metabolic behavior of A. brasiliensis ATCC9642 in SSF at high glucose concentrations through a proteomic approach. Online respirometric analysis provided reproducible samples for secretomic studies when the maximum CO 2 production rate occurred, ensuring consistent physiological states. Extracellular extracts from SSF cultures were treated by SDS-PAGE, digested with trypsin, and analyzed by LC-MS/MS. Of 531 sequences identified, 207 proteins were analyzed. Twenty-five were identified as the most abundant unregulated proteins; 87 were found to be up-regulated and 95 were down-regulated with increasing glucose concentration. Of the regulated proteins, 120 were enzymes, most involved in the metabolism of carbohydrates (51), amino acids (23), and nucleotides (9). This study shows the high protein secretory activity of A. brasiliensis under SSF conditions. High glucose concentration favors catabolic activities, while some stress-related proteins and those involved in proteolysis are down-regulated.

The Reproductive System.

PubMed

Pask, Andrew

2016-01-01

Correct sexual development is arguably the most important trait in an organism's life history since it is directly related to its genetic fitness. The developing gonad houses the germ cells, the only legacy we pass on to subsequent generations. Given the pivotal importance of correct reproductive function, it is confounding that disorders of sex development (DSDs) are among the most common congenital abnormalities in humans (Lee et al. J Pediatr Urol 8(6):611-615, 2012). Urogenital development is a highly complex process involving coordinated interactions between molecular and hormonal pathways in a tightly regulated order. The controls that regulate some of the key events in this process are beginning to be unraveled. This chapter provides an overview of our understanding of urogenital development from the gonads to the urogenital ducts and external genitalia.

Gordon Conference on Microbial Adhesion

DTIC Science & Technology

1988-07-01

00-11:45 a.m. * antigen A and dextranase in Streptococcus mutans colonization. B. Uhlin, Regulation of pilus-adhesin 11:45-12:30 p.m.expression in E...surfaces. In addition, the role of bacterium-bacterium co- aggregation processes was considered. Why does Streptococcus sanguis have such a high affinity...attachment of bacteria to saliva-coated surfaces? Why is S. mutans poorly adherent yet highly cariogenic? What are the characteri-tics of strcptococcal

NASA Principal Center for Review of Clean Air Act Regulations

NASA Technical Reports Server (NTRS)

Clark-Ingram, Marceia; Munafo, Paul M. (Technical Monitor)

2002-01-01

The Clean Air Act (CAA) regulations have greatly impacted materials and processes utilized in the manufacture of aerospace hardware. Code JE/ NASA's Environmental Management Division at NASA Headquarters recognized the need for a formal, Agency-wide review process of CAA regulations. Marshall Space Flight Center (MSFC) was selected as the 'Principal Center for Review of Clean Air Act Regulations'. This presentation describes the centralized support provided by MSFC for the management and leadership of NASA's CAA regulation review process.

Incremental Validity of the Subscales of the Emotional Regulation Related to Testing Scale for Predicting Test Anxiety

ERIC Educational Resources Information Center

Feldt, Ronald; Lindley, Kyla; Louison, Rebecca; Roe, Allison; Timm, Megan; Utinkova, Nikola

2015-01-01

The Emotional Regulation Related to Testing Scale (ERT Scale) assesses strategies students use to regulate emotion related to academic testing. It has four dimensions: Cognitive Appraising Processes (CAP), Emotion-Focusing Processes (EFP), Task-Focusing Processes (TFP), and Regaining Task-Focusing Processes (RTFP). The study examined the factor…

Dealing with emotions when the ability to cry is hampered: emotion processing and regulation in patients with primary Sjögren's syndrome.

PubMed

van Leeuwen, Ninke; Bossema, Ercolie R; van Middendorp, Henriët; Kruize, Aike A; Bootsma, Hendrika; Bijlsma, Johannes W J; Geenen, Rinie

2012-01-01

The hampered ability to cry in patients with Sjögren's syndrome may affect their ways of dealing with emotions. The aim of this study was to examine differences in emotion processing and regulation between people with and without Sjögren's syndrome and correlations of emotion processing and regulation with mental well-being. In 300 patients with primary Sjögren's syndrome and 100 demographically matched control participants (mean age 56.8 years, 93% female), emotion processing (affect intensity and alexithymia, i.e. difficulty identifying and describing feelings), emotion regulation (cognitive reappraisal, suppression and expression of emotions), and mental well-being were assessed. Criteria for clinical alexithymia applied to 22% of the patients and 12% of the control participants; patients had significantly more difficulty identifying feelings than control participants. No other significant differences in emotion processing and emotion regulation were found. In patients, the emotion processing styles affect intensity and alexithymia (0.32

Genetic and Attachment Influences on Adolescents' Regulation of Autonomy and Aggressiveness

ERIC Educational Resources Information Center

Zimmermann, Peter; Mohr, Cornelia; Spangler, Gottfried

2009-01-01

Background: Adolescence is a time when intense emotions are elicited within the parent-adolescent relationship, often when autonomy subjectively is endangered. As emotion dysregulation is one of the risk processes for the development of psychopathology, adolescence may be perceived as a highly sensitive period for maladjustment. Inter-individual…

78 FR 18321 - International Code Council: The Update Process for the International Codes and Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... for Residential Construction in High Wind Regions. ICC 700: National Green Building Standard The..., coordinated, and necessary to regulate the built environment. Federal agencies frequently use these codes and... International Codes and Standards consist of the following: ICC Codes International Building Code. International...

75 FR 19944 - International Code Council: The Update Process for the International Codes and Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-16

... for Residential Construction in High Wind Areas. ICC 700: National Green Building Standard. The... Codes and Standards that are comprehensive, coordinated, and necessary to regulate the built environment... International Codes and Standards consist of the following: ICC Codes International Building Code. International...

34 CFR 668.141 - Scope.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 3 2011-07-01 2011-07-01 false Scope. 668.141 Section 668.141 Education Regulations of...; Specification of Passing Score; Approval of State Process § 668.141 Scope. (a) This subpart sets forth the provisions under which a student who has neither a high school diploma nor its recognized equivalent may...

34 CFR 668.141 - Scope.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false Scope. 668.141 Section 668.141 Education Regulations of...; Specification of Passing Score; Approval of State Process § 668.141 Scope. (a) This subpart sets forth the provisions under which a student who has neither a high school diploma nor its recognized equivalent may...

Transcriptomic analysis reveals the gene expression profile that specifically responds to IBA during adventitious rooting in mung bean seedlings.

PubMed

Li, Shi-Weng; Shi, Rui-Fang; Leng, Yan; Zhou, Yuan

2016-01-12

Auxin plays a critical role in inducing adventitious rooting in many plants. Indole-3-butyric acid (IBA) is the most widely employed auxin for adventitious rooting. However, the molecular mechanisms by which auxin regulate the process of adventitious rooting are less well known. The RNA-Seq data analysis indicated that IBA treatment greatly increased the amount of clean reads and the amount of expressed unigenes by 24.29 % and 27.42 % and by 4.3 % and 5.04 % at two time points, respectively, and significantly increased the numbers of unigenes numbered with RPKM = 10-100 and RPKM = 500-1000 by 13.04 % and 3.12 % and by 24.66 % and 108.2 % at two time points, respectively. Gene Ontology (GO) enrichment analysis indicated that the enrichment of down-regulated GOs was 2.87-fold higher than that of up-regulated GOs at stage 1, suggesting that IBA significantly down-regulated gene expression at 6 h. The GO functional category indicated that IBA significantly up- or down-regulated processes associated with auxin signaling, ribosome assembly and protein synthesis, photosynthesis, oxidoreductase activity and extracellular region, secondary cell wall biogenesis, and the cell wall during the development process. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicated that ribosome biogenesis, plant hormone signal transduction, pentose and glucuronate interconversions, photosynthesis, phenylpropanoid biosynthesis, sesquiterpenoid and triterpenoid biosynthesis, ribosome, cutin, flavonoid biosynthesis, and phenylalanine metabolism were the pathways most highly regulated by IBA. A total of 6369 differentially expressed (2-fold change > 2) unigenes (DEGs) with 3693 (58 %) that were up-regulated and 2676 (42 %) down-regulated, 5433 unigenes with 2208 (40.6 %) that were up-regulated and 3225 (59.4 %) down-regulated, and 7664 unigenes with 3187 (41.6 %) that were up-regulated and 4477 (58.4 %) down-regulated were detected at stage 1, stage 2, and between stage 1 and stage 2, respectively, suggesting that IBA treatment increased the number of DEGs. A total of 143 DEGs specifically involved in plant hormone signaling and 345 transcription factor (TF) genes were also regulated by IBA. qRT-PCR validation of the 36 genes with known functions indicated a strong correlation with the RNA-Seq data. The changes in GO functional categories, KEGG pathways, and global DEG profiling during adventitious rooting induced by IBA were analyzed. These results provide valuable information about the molecular traits of IBA regulation of adventitious rooting.

[Good for your health? An analysis of the requirements for scientific substantiation in European health claims regulation].

PubMed

Todt, Oliver; Luján, José Luis

2016-06-01

To identify the various types of evidence, as well as their relative importance in European health claims regulation, in order to analyze the consequences for consumer protection of the requirements for scientific substantiation in this regulation. Qualitative analysis of various documents relevant to the regulatory process, particularly as to the implications of the standards of proof for the functional food market, as well as consumer behavior. European regulation defines a hierarchy of evidence that turns randomized controlled trials into a necessary and sufficient condition for health claim authorizations. Consumer protection can be interpreted in different manners. High standards of proof protect consumers from false information about the health outcomes of functional foods, while lower standards lead to more, albeit less accurate information about such outcomes being available to consumers.

Mitochondrial activity in the regulation of stem cell self-renewal and differentiation.

PubMed

Khacho, Mireille; Slack, Ruth S

2017-12-01

Mitochondria are classically known as the essential energy producers in cells. As such, the activation of mitochondrial metabolism upon cellular differentiation was deemed a necessity to fuel the high metabolic needs of differentiated cells. However, recent studies have revealed a direct role for mitochondrial activity in the regulation of stem cell fate and differentiation. Several components of mitochondrial metabolism and respiration have now been shown to regulate different aspects of stem cell differentiation through signaling, transcriptional, proteomic and epigenetic modulations. In light of these findings mitochondrial metabolism is no longer considered a consequence of cellular differentiation, but rather a key regulatory mechanism of this process. This review will focus on recent progress that defines mitochondria as the epicenters for the regulation of stem cell fate decisions. Copyright © 2017 Elsevier Ltd. All rights reserved.

P53 protein in proliferation, repair and apoptosis of cells.

PubMed

Wawryk-Gawda, Ewelina; Chylińska-Wrzos, Patrycja; Lis-Sochocka, Marta; Chłapek, Katarzyna; Bulak, Kamila; Jędrych, Marian; Jodłowska-Jędrych, Barbara

2014-05-01

The p53 protein is an important factor of many intra- and extracellular processes. This protein regulates the repair of cellular DNA and induces apoptosis. It is also responsible for the regulation of the senescence and the cell entering the subsequent stages of the cellular cycle. The protein p53 is also involved in inhibiting angiogenesis and the induction of oxidative shock. In our study, we examined the activity of p53 protein in the uterine epithelial cells in rats treated with cladribine. Its action is mainly based on apoptosis induction. We compared the activity of p53 protein in cells with a high apoptosis index and in cells with active repair mechanisms and high proliferation index. We observed stronger p53 protein expression in the epithelial cells of the materials taken 24 h after the last dose of 2-CdA associated with the active process of apoptosis and inhibition of proliferation. After 4 weeks from the last dose of cladribine, the stronger expression of p53 protein was associated with both the existing changes in the cell's genome, the effects of the ongoing repair mechanisms, as well as the high proliferation activity.

High-risk medical devices, children and the FDA: regulatory challenges facing pediatric mechanical circulatory support devices.

PubMed

Almond, Christopher S D; Chen, Eric A; Berman, Michael R; Less, Joanne R; Baldwin, J Timothy; Linde-Feucht, Sarah R; Hoke, Tracey R; Pearson, Gail D; Jenkins, Kathy; Duncan, Brian W; Zuckerman, Bram D

2007-01-01

Pediatric mechanical circulatory support is a critical unmet need in the United States. Infant- and child-sized ventricular assist devices are currently being developed largely through federal contracts and grants through the National Heart, Lung, and Blood Institute (NHLBI). Human testing and marketing of high-risk devices for children raises epidemiologic and regulatory issues that will need to be addressed. Leaders from the US Food and Drug Administration (FDA), NHLBI, academic pediatric community, and industry convened in January 2006 for the first FDA Workshop on the Regulatory Process for Pediatric Mechanical Circulatory Support Devices. The purpose was to provide the pediatric community with an overview of the federal regulatory process for high-risk medical devices and to review the challenges specific to the development and regulation of pediatric mechanical circulatory support devices. Pediatric mechanical circulatory support present significant epidemiologic, logistic, and financial challenges to industry, federal regulators, and the pediatric community. Early interactions with the FDA, shared appreciation of challenges, and careful planning will be critical to avoid unnecessary delays in making potentially life-saving devices available for children. Collaborative efforts to address these challenges are warranted.

Identification of small RNAs abundant in Burkholderia cenocepacia biofilms reveal putative regulators with a potential role in carbon and iron metabolism.

PubMed

Sass, Andrea; Kiekens, Sanne; Coenye, Tom

2017-11-15

Small RNAs play a regulatory role in many central metabolic processes of bacteria, as well as in developmental processes such as biofilm formation. Small RNAs of Burkholderia cenocepacia, an opportunistic pathogenic beta-proteobacterium, are to date not well characterised. To address that, we performed genome-wide transcriptome structure analysis of biofilm grown B. cenocepacia J2315. 41 unannotated short transcripts were identified in intergenic regions of the B. cenocepacia genome. 15 of these short transcripts, highly abundant in biofilms, widely conserved in Burkholderia sp. and without known function, were selected for in-depth analysis. Expression profiling showed that most of these sRNAs are more abundant in biofilms than in planktonic cultures. Many are also highly abundant in cells grown in minimal media, suggesting they are involved in adaptation to nutrient limitation and growth arrest. Their computationally predicted targets include a high proportion of genes involved in carbon metabolism. Expression and target genes of one sRNA suggest a potential role in regulating iron homoeostasis. The strategy used for this study to detect sRNAs expressed in B. cenocepacia biofilms has successfully identified sRNAs with a regulatory function.

Wnt5a Increases the Glycolytic Rate and the Activity of the Pentose Phosphate Pathway in Cortical Neurons

PubMed Central

Cisternas, Pedro; Salazar, Paulina; Silva-Álvarez, Carmen; Barros, L. Felipe

2016-01-01

In the last few years, several reports have proposed that Wnt signaling is a general metabolic regulator, suggesting a role for this pathway in the control of metabolic flux. Wnt signaling is critical for several neuronal functions, but little is known about the correlation between this pathway and energy metabolism. The brain has a high demand for glucose, which is mainly used for energy production. Neurons use energy for highly specific processes that require a high energy level, such as maintaining the electrical potential and synthesizing neurotransmitters. Moreover, an important metabolic impairment has been described in all neurodegenerative disorders. Despite the key role of glucose metabolism in the brain, little is known about the cellular pathways involved in regulating this process. We report here that Wnt5a induces an increase in glucose uptake and glycolytic rate and an increase in the activity of the pentose phosphate pathway; the effects of Wnt5a require the intracellular generation of nitric oxide. Our data suggest that Wnt signaling stimulates neuronal glucose metabolism, an effect that could be important for the reported neuroprotective role of Wnt signaling in neurodegenerative disorders. PMID:27688915

Wnt5a Increases the Glycolytic Rate and the Activity of the Pentose Phosphate Pathway in Cortical Neurons.

PubMed

Cisternas, Pedro; Salazar, Paulina; Silva-Álvarez, Carmen; Barros, L Felipe; Inestrosa, Nibaldo C

In the last few years, several reports have proposed that Wnt signaling is a general metabolic regulator, suggesting a role for this pathway in the control of metabolic flux. Wnt signaling is critical for several neuronal functions, but little is known about the correlation between this pathway and energy metabolism. The brain has a high demand for glucose, which is mainly used for energy production. Neurons use energy for highly specific processes that require a high energy level, such as maintaining the electrical potential and synthesizing neurotransmitters. Moreover, an important metabolic impairment has been described in all neurodegenerative disorders. Despite the key role of glucose metabolism in the brain, little is known about the cellular pathways involved in regulating this process. We report here that Wnt5a induces an increase in glucose uptake and glycolytic rate and an increase in the activity of the pentose phosphate pathway; the effects of Wnt5a require the intracellular generation of nitric oxide. Our data suggest that Wnt signaling stimulates neuronal glucose metabolism, an effect that could be important for the reported neuroprotective role of Wnt signaling in neurodegenerative disorders.

Synthesis and characterization of TEP-EDTA-regulated bioactive hydroxyapatite

NASA Astrophysics Data System (ADS)

Haders, Daniel Joseph, II

Hydroxyapatite (HA), Ca10(PO4)6(OH) 2, the stoichiometric equivalent of the ceramic phase of bone, is the preferred material for hard tissue replacement due to its bioactivity. However, bioinert metals are utilized in load-bearing orthopedic applications due to the poor mechanical properties of HA. Consequently, attention has been given to HA coatings for metallic orthopedic implants to take advantage of the bioactivity of HA and the mechanical properties of metals. Commercially, the plasma spray process (PS-HA) is the method most often used to deposit HA films on metallic implants. Since its introduction in the 1980's, however, concerns have been raised about the consequences of PS-HA's low crystallinity, lack of phase purity, lack of film-substrate chemical adhesion, passivation properties, and difficulty in coating complex geometries. Thus, there is a need to develop inexpensive reproducible next-generation HA film deposition techniques, which deposit high crystallinity, phase pure, adhesive, passivating, conformal HA films on clinical metallic substrates. The aim of this dissertation was to intelligently synthesize and characterize the material and biological properties of HA films on metallic substrates synthesized by hydrothermal crystallization, using thermodynamic phase diagrams as the starting point. In three overlapping interdisciplinary studies the potential of using ethylenediamine-tetraacetic acid/triethyl phosphate (EDTA/TEP) doubly regulated hydrothermal crystallization to deposit HA films, the TEP-regulated, time-and-temperature-dependent process by which films were deposited, and the bioactivity of crystallographically engineered films were investigated. Films were crystallized in a 0.232 molal Ca(NO3)2-0.232 molal EDTA-0.187 molal TEP-1.852 molal KOH-H2O chemical system at 200°C. Thermodynamic phase diagrams demonstrated that the chosen conditions were expected to produce Ca-P phase pure HA, which was experimentally confirmed. EDTA regulation of Ca2+ concentration enabled the HA crystallization process to be growth dominated, producing films composed of high crystallinity, hexagonal grains on multiple metallic substrates. TEP regulation of HA crystallization enabled the deposition of an adhesive CaTiO3 intermediate layer, and then HA in a continuous, phase sequenced process on Ti6Al4V substrates, the first such process reported in the hydrothermal HA literature. The HA film was found to be deposited by a passivating competitive growth mechanism that enabled the [0001] crystallographic orientation of hexagonal single crystals to be engineered with synthesis time. Bioactivity analysis demonstrated that films were bioactive and bone bonding. Together, these results suggest that these HA films are candidates for use on metallic orthopedic implants, namely Ti6Al4V.

48 CFR 15.101-1 - Tradeoff process.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Tradeoff process. 15.101-1 Section 15.101-1 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Source Selection Processes and Techniques 15.101-1...

Examining Middle School Science Student Self-Regulated Learning in a Hypermedia Learning Environment through Microanalysis

NASA Astrophysics Data System (ADS)

Mandell, Brian E.

The purpose of the present embedded mixed method study was to examine the self-regulatory processes used by high, average, and low achieving seventh grade students as they learned about a complex science topic from a hypermedia learning environment. Thirty participants were sampled. Participants were administered a number of measures to assess their achievement and self-efficacy. In addition, a microanalytic methodology, grounded in Zimmerman's cyclical model of self-regulated learning, was used to assess student self-regulated learning. It was hypothesized that there would be modest positive correlations between Zimmerman's three phases of self-regulated learning, that high achieving science students would deploy more self-regulatory subprocesses than average and low achieving science students, that high achieving science students would have higher self-efficacy beliefs to engage in self-regulated learning than average and low achieving science students, and that low achieving science students would over-estimate their self-efficacy for performance beliefs, average achieving science students would slightly overestimate their self-efficacy for performance beliefs, and high achieving science students would under-estimate their self-efficacy for performance beliefs. All hypotheses were supported except for the high achieving science students who under-estimated their self-efficacy for performance beliefs on the Declarative Knowledge Measure and slightly overestimated their self-efficacy for performance beliefs on the Conceptual Knowledge Measure. Finally, all measures of self-regulated learning were combined and entered into a regression formula to predict the students' scores on the two science tests, and it was revealed that the combined measure predicted 91% of the variance on the Declarative Knowledge Measure and 92% of the variance on the Conceptual Knowledge Measure. This study adds hypermedia learning environments to the contexts that the microanalytic methodology has been successfully administered. Educational implications and limitations to the study are also discussed.

High Throughput, High Content Screening for Novel Pigmentation Regulators Using a Keratinocyte/Melanocyte Co-culture System

PubMed Central

Lee, Ju Hee; Chen, Hongxiang; Kolev, Vihren; Aull, Katherine H.; Jung, Inhee; Wang, Jun; Miyamoto, Shoko; Hosoi, Junichi; Mandinova, Anna; Fisher, David E.

2014-01-01

Skin pigmentation is a complex process including melanogenesis within melanocytes and melanin transfer to the keratinocytes. To develop a comprehensive screening method for novel pigmentation regulators, we used immortalized melanocytes and keratinocytes in co-culture to screen large numbers of compounds. High-throughput screening plates were subjected to digital automated microscopy to quantify the pigmentation via brightfield microscopy. Compounds with pigment suppression were secondarily tested for their effects on expression of MITF and several pigment regulatory genes, and further validated in terms of non-toxicity to keratinocytes/melanocytes and dose dependent activity. The results demonstrate a high-throughput, high-content screening approach, which is applicable to the analysis of large chemical libraries using a co-culture system. We identified candidate pigmentation inhibitors from 4,000 screened compounds including zoxazolamine, 3-methoxycatechol, and alpha-mangostin, which were also shown to modulate expression of MITF and several key pigmentation factors, and are worthy of further evaluation for potential translation to clinical use. PMID:24438532

Self-regulation and selective exposure: the impact of depleted self-regulation resources on confirmatory information processing.

PubMed

Fischer, Peter; Greitemeyer, Tobias; Frey, Dieter

2008-03-01

In the present research, the authors investigated the impact of self-regulation resources on confirmatory information processing, that is, the tendency of individuals to systematically prefer standpoint-consistent information to standpoint-inconsistent information in information evaluation and search. In 4 studies with political and economic decision-making scenarios, it was consistently found that individuals with depleted self-regulation resources exhibited a stronger tendency for confirmatory information processing than did individuals with nondepleted self-regulation resources. Alternative explanations based on processes of ego threat, cognitive load, and mood were ruled out. Mediational analyses suggested that individuals with depleted self-regulation resources experienced increased levels of commitment to their own standpoint, which resulted in increased confirmatory information processing. In sum, the impact of ego depletion on confirmatory information search seems to be more motivational than cognitive in nature.

Zooming in on children's behavior during delay of gratification: Disentangling impulsigenic and volitional processes underlying self-regulation.

PubMed

Neuenschwander, Regula; Blair, Clancy

2017-02-01

When delaying gratification, both motivational and regulatory processes are likely to be at play; however, the relative contributions of motivational and regulatory influences on delay behavior are unclear. By examining behavioral responses during a delay task, this study sought to examine the motivational (anticipatory behavior) and regulatory mechanisms (executive function and self-control strategies) underlying children's self-regulation. The participants, 65 5- to 9-year-old children (M age =7.19years, SD=0.89), were video-recorded during a delay procedure and later coded for anticipatory behaviors (e.g., gazing intensely at the tablet) and self-control strategies. Children also completed two executive function (EF) tasks. We found that anticipatory behavior was curvilinearly related to delay time. Children showing either very low or very high levels of anticipatory behavior were not able to wait the entire time. Furthermore, our results indicated that anticipatory behavior interacted with EF to predict delay time. Specifically, anticipatory behavior was negatively related to delay time only if EF abilities were low. Finally, self-control strategies also interacted with EF to predict children's ability to delay. Spontaneous engagement in self-control strategies such as fidgeting and engagement in alternative activities were beneficial for children with low EF but were unrelated to delay time for children with high EF. Results indicate the value of examining motivational and regulatory influences on delay behavior. Lapses in self-regulation may be due to the combination of powerful impulsigenic (i.e., anticipatory behavior) and weak volitional processes (i.e., EF, self-control strategies). Copyright © 2016. Published by Elsevier Inc.

A new tomato NAC (NAM/ATAF1/2/CUC2) transcription factor, SlNAC4, functions as a positive regulator of fruit ripening and carotenoid accumulation.

PubMed

Zhu, Mingku; Chen, Guoping; Zhou, Shuang; Tu, Yun; Wang, Yi; Dong, Tingting; Hu, Zongli

2014-01-01

Fruit ripening in tomato (Solanum lycopersicum) is a complicated development process affected by both endogenous hormonal and genetic regulators and external signals. Although the role of NOR, a member of the NAC domain family, in mediating tomato fruit ripening has been established, its underlying molecular mechanisms remain unclear. To explore further the role of NAC transcription factors in fruit ripening, we characterized a new tomato NAC domain protein, named SlNAC4, which shows high accumulation in sepal and at the onset of fruit ripening. Various stress treatments including wounding, NaCl, dehydration and low temperature significantly increased the expression of SlNAC4. Reduced expression of SlNAC4 by RNA interference (RNAi) in tomato resulted in delayed fruit ripening, suppressed Chl breakdown and decreased ethylene synthesis mediated mainly through reduced expression of ethylene biosynthesis genes of system-2, and reduced carotenoids by alteration of the carotenoid pathway flux. Transgenic tomato fruits also displayed significant down-regulation of multiple ripening-associated genes, indicating that SlNAC4 functions as a positive regulator of fruit ripening by affecting ethylene synthesis and carotenoid accumulation. Moreover, we also noted that SlNAC4 could not be induced by ethylene and may function upstream of the ripening regulator RIN and positively regulate its expression. Yeast two-hybrid assay further revealed that SlNAC4 could interact with both RIN and NOR protein. These results suggested that ethylene-dependent and -independent processes are regulated by SlNAC4 in the fruit ripening regulatory network.

hnRNP-Q1 represses nascent axon growth in cortical neurons by inhibiting Gap-43 mRNA translation

PubMed Central

Williams, Kathryn R.; McAninch, Damian S.; Stefanovic, Snezana; Xing, Lei; Allen, Megan; Li, Wenqi; Feng, Yue; Mihailescu, Mihaela Rita; Bassell, Gary J.

2016-01-01

Posttranscriptional regulation of gene expression by mRNA-binding proteins is critical for neuronal development and function. hnRNP-Q1 is an mRNA-binding protein that regulates mRNA processing events, including translational repression. hnRNP-Q1 is highly expressed in brain tissue, suggesting a function in regulating genes critical for neuronal development. In this study, we have identified Growth-associated protein 43 (Gap-43) mRNA as a novel target of hnRNP-Q1 and have demonstrated that hnRNP-Q1 represses Gap-43 mRNA translation and consequently GAP-43 function. GAP-43 is a neuronal protein that regulates actin dynamics in growth cones and facilitates axonal growth. Previous studies have identified factors that regulate Gap-43 mRNA stability and localization, but it remains unclear whether Gap-43 mRNA translation is also regulated. Our results reveal that hnRNP-Q1 knockdown increased nascent axon length, total neurite length, and neurite number in mouse embryonic cortical neurons and enhanced Neuro2a cell process extension; these phenotypes were rescued by GAP-43 knockdown. Additionally, we have identified a G-quadruplex structure in the 5′ untranslated region of Gap-43 mRNA that directly interacts with hnRNP-Q1 as a means to inhibit Gap-43 mRNA translation. Therefore hnRNP-Q1–mediated repression of Gap-43 mRNA translation provides an additional mechanism for regulating GAP-43 expression and function and may be critical for neuronal development. PMID:26658614

Von Willebrand factor regulation of blood vessel formation.

PubMed

Randi, Anna M; Smith, Koval E; Castaman, Giancarlo

2018-06-04

Several important physiological processes, from permeability to inflammation to haemostasis, take place at the vessel wall and are regulated by endothelial cells (EC). Thus, proteins that have been identified as regulators of one process are increasingly found to be involved in other vascular functions. Such is the case for Von Willebrand Factor (VWF), a large glycoprotein best known for its critical role in haemostasis. In vitro and in vivo studies have shown that lack of VWF causes enhanced vascularisation, both constitutively and following ischemia. This evidence is supported by studies on blood outgrowth endothelial cells (BOEC) from patients with lack of VWF synthesis (type 3 von Willebrand disease [VWD]). The molecular pathways are likely to involve VWF binding partners, such as integrin αvβ3, and components of Weibel Palade bodies (WPB), such as Angiopoietin-2 and Galectin-3, whose storage is regulated by VWF; these converge on the master regulator of angiogenesis and endothelial homeostasis, vascular endothelial growth factor (VEGF) signalling. Recent studies suggest that the roles of VWF may be tissue-specific. The ability of VWF to regulate angiogenesis has clinical implications for a subset of VWD patients with severe, intractable gastrointestinal bleeding due to vascular malformations. In this article, we review the evidence showing that VWF is involved in blood vessel formation, discuss the role of VWF high molecular weight multimers in regulating angiogenesis, and the value of studies on BOEC in developing a precision medicine approach to validate novel treatments for angiodysplasia in congenital VWD and acquired von Willebrand syndrome. Copyright © 2018 American Society of Hematology.

Self-Regulated Learning from Illustrated Text: Eye Movement Modelling to Support Use and Regulation of Cognitive Processes during Learning from Multimedia

ERIC Educational Resources Information Center

Scheiter, Katharina; Schubert, Carina; Schüler, Anne

2018-01-01

Background: When learning with text and pictures, learners often fail to adequately process the materials, which can be explained as a failure to self-regulate one's learning by choosing adequate cognitive learning processes. Eye movement modelling examples (EMME) showing how to process multimedia instruction have improved elementary school…

Individual and Combined Roles of the Master Regulators AphA and LuxR in Control of the Vibrio harveyi Quorum-Sensing Regulon

PubMed Central

van Kessel, Julia C.; Rutherford, Steven T.; Shao, Yi; Utria, Alan F.

2013-01-01

Bacteria use a chemical communication process called quorum sensing to control transitions between individual and group behaviors. In the Vibrio harveyi quorum-sensing circuit, two master transcription factors, AphA and LuxR, coordinate the quorum-sensing response. Here we show that AphA regulates 167 genes, LuxR regulates 625 genes, and they coregulate 77 genes. LuxR strongly controls genes at both low cell density and high cell density, suggesting that it is the major quorum-sensing regulator. In contrast, AphA is absent at high cell density and acts to fine-tune quorum-sensing gene expression at low cell density. We examined two loci as case studies of coregulation by AphA and LuxR. First, AphA and LuxR directly regulate expression of the genes encoding the quorum-regulatory small RNAs Qrr2, Qrr3, and Qrr4, the consequence of which is a specifically timed transition between the individual and the group life-styles. Second, AphA and LuxR repress type III secretion system genes but at different times and to different extents. The consequence of this regulation is that type III secretion is restricted to a peak at mid-cell density. Thus, the asymmetric production of AphA and LuxR coupled with differences in their strengths and timing of target gene regulation generate a precise temporal pattern of gene expression. PMID:23204455

iTRAQ-based analysis of changes in the cassava root proteome reveals pathways associated with post-harvest physiological deterioration.

PubMed

Owiti, Judith; Grossmann, Jonas; Gehrig, Peter; Dessimoz, Christophe; Laloi, Christophe; Hansen, Maria Benn; Gruissem, Wilhelm; Vanderschuren, Hervé

2011-07-01

The short storage life of harvested cassava roots is an important constraint that limits the full potential of cassava as a commercial food crop in developing countries. We investigated the molecular changes during physiological deterioration of cassava root after harvesting using isobaric tags for relative and absolute quantification (iTRAQ) of proteins in soluble and non-soluble fractions prepared during a 96 h post-harvest time course. Combining bioinformatic approaches to reduce information redundancy for unsequenced or partially sequenced plant species, we established a comprehensive proteome map of the cassava root and identified quantitatively regulated proteins. Up-regulation of several key proteins confirmed that physiological deterioration of cassava root after harvesting is an active process, with 67 and 170 proteins, respectively, being up-regulated early and later after harvesting. This included regulated proteins that had not previously been associated with physiological deterioration after harvesting, such as linamarase, glutamic acid-rich protein, hydroxycinnamoyl transferase, glycine-rich RNA binding protein, β-1,3-glucanase, pectin methylesterase, maturase K, dehydroascorbate reductase, allene oxide cyclase, and proteins involved in signal pathways. To confirm the regulation of these proteins, activity assays were performed for selected enzymes. Together, our results show that physiological deterioration after harvesting is a highly regulated complex process involving proteins that are potential candidates for biotechnology approaches to reduce such deterioration. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

About the dangers, costs and benefits of living an aerobic lifestyle.

PubMed

Knoefler, Daniela; Leichert, Lars I O; Thamsen, Maike; Cremers, Claudia M; Reichmann, Dana; Gray, Michael J; Wholey, Wei-Yun; Jakob, Ursula

2014-08-01

The era in which ROS (reactive oxygen species) were simply the 'bad boys of biology' is clearly over. High levels of ROS are still rightfully considered to be toxic to many cellular processes and, as such, contribute to disease conditions and cell death. However, the high toxicity of ROS is also extremely beneficial, particularly as it is used to kill invading micro-organisms during mammalian host defence. Moreover, a transient, often more localized, increase in ROS levels appears to play a major role in signal transduction processes and positively affects cell growth, development and differentiation. At the heart of all these processes are redox-regulated proteins, which use oxidation-sensitive cysteine residues to control their function and by extension the function of the pathways that they are part of. Our work has contributed to changing the view about ROS through: (i) our characterization of Hsp33 (heat-shock protein 33), one of the first redox-regulated proteins identified, whose function is specifically activated by ROS, (ii) the development of quantitative tools that reveal extensive redox-sensitive processes in bacteria and eukaryotes, and (iii) the discovery of a link between early exposure to oxidants and aging. Our future research programme aims to generate an integrated and system-wide view of the beneficial and deleterious effects of ROS with the central goal to develop more effective antioxidant strategies and more powerful antimicrobial agents.

Microarray analysis of gene expression patterns in the leaf during potato tuberization in the potato somatic hybrid Solanum tuberosum and Solanum etuberosum.

PubMed

Tiwari, Jagesh Kumar; Devi, Sapna; Sundaresha, S; Chandel, Poonam; Ali, Nilofer; Singh, Brajesh; Bhardwaj, Vinay; Singh, Bir Pal

2015-06-01

Genes involved in photoassimilate partitioning and changes in hormonal balance are important for potato tuberization. In the present study, we investigated gene expression patterns in the tuber-bearing potato somatic hybrid (E1-3) and control non-tuberous wild species Solanum etuberosum (Etb) by microarray. Plants were grown under controlled conditions and leaves were collected at eight tuber developmental stages for microarray analysis. A t-test analysis identified a total of 468 genes (94 up-regulated and 374 down-regulated) that were statistically significant (p ≤ 0.05) and differentially expressed in E1-3 and Etb. Gene Ontology (GO) characterization of the 468 genes revealed that 145 were annotated and 323 were of unknown function. Further, these 145 genes were grouped based on GO biological processes followed by molecular function and (or) PGSC description into 15 gene sets, namely (1) transport, (2) metabolic process, (3) biological process, (4) photosynthesis, (5) oxidation-reduction, (6) transcription, (7) translation, (8) binding, (9) protein phosphorylation, (10) protein folding, (11) ubiquitin-dependent protein catabolic process, (12) RNA processing, (13) negative regulation of protein, (14) methylation, and (15) mitosis. RT-PCR analysis of 10 selected highly significant genes (p ≤ 0.01) confirmed the microarray results. Overall, we show that candidate genes induced in leaves of E1-3 were implicated in tuberization processes such as transport, carbohydrate metabolism, phytohormones, and transcription/translation/binding functions. Hence, our results provide an insight into the candidate genes induced in leaf tissues during tuberization in E1-3.

Linking dynamics of transport timescale and variations of hypoxia in the Chesapeake Bay

NASA Astrophysics Data System (ADS)

Hong, Bo; Shen, Jian

2013-11-01

Dissolved oxygen (DO) replenishment in the bottom waters of an estuary depends on physical processes that are significantly influenced by external forcings. The vertical exchange time (VET) is introduced in this study to quantify the physical processes that regulate the DO replenishment in the Chesapeake Bay. A 3-D numerical model was applied to simulate the circulation, VET, and DO. Results indicate that VET is a suitable parameter for evaluating the bottom DO condition over both seasonal and interannual timescales. The VET is negatively correlated with the bottom DO. Hypoxia (DO <2 mg L-1) will develop in the Bay when VET is greater than 23 days in summer if mean total DO consumption rate is about 0.3 g O2 m-3 d-1. This critical VET value may vary around 23 days when the total DO consumption rate changes. The VET volume (volume of water mass with VET >23 days) can account for 77% of variations of hypoxic volume in the main Bay. The VET cannot explain all the DO variations as it can only account for the contribution of physical processes that regulate DO replenishment. It is found that the short-term vertical exchange process is highly controlled by the wind forcing. The VET volume decreases when the high-speed wind events are frequent. The summertime VET volume is less sensitive to short-term variations (pulses) of river discharge. It is sensitive to the total amount of river discharge and the high VET volume can be expected in the wet year.

PC5-A-mediated processing of pro-neurotensin in early compartments of the regulated secretory pathway of PC5-transfected PC12 cells.

PubMed

Barbero, P; Rovère, C; De Bie, I; Seidah, N; Beaudet, A; Kitabgi, P

1998-09-25

Among the members of the proprotein convertase (PC) family, PC1 and PC2 have well established roles as prohormone convertases. Another good candidate for this role is PC5-A that has been shown to be present in the regulated secretory pathway of certain neuroendocrine tissues, but evidence that it can process prohormones is lacking. To determine whether PC5-A could function as a prohormone convertase and to compare its cleavage specificity with that of PC1 and PC2, we stably transfected the rat pheochromocytoma PC12 cell line with PC5-A and analyzed the biosynthesis and subcellular localization of the enzyme, as well as its ability to process pro-neurotensin/neuromedin N (pro-NT/NN) into active peptides. Our data showed that in transfected PC12 cells, PC5-A was converted from its 126-kDa precursor form into a 117-kDa mature form and, to a lesser extent, into a C-terminally truncated 65-kDa form of the 117-kDa product. Metabolic and immunochemical studies showed that PC5-A was sorted to early compartments of the regulated secretory pathway where it colocalized with immunoreactive NT. Furthermore, pro-NT/NN was processed in these compartments according to a pattern that differed from that previously described in PC1- and PC2-transfected PC12 cells. This pattern resembled that previously reported for pro-NT/NN processing in the adrenal medulla, a tissue known to express high levels of PC5-A. Altogether, these data demonstrate for the first time the ability of PC5-A to function as a prohormone convertase in the regulated secretory pathway and suggest a role for this enzyme in the physiological processing of pro-NT/NN.

Protocol and practice in the adaptive management of waterfowl harvests

USGS Publications Warehouse

Johnson, F.; Williams, K.

1999-01-01

Waterfowl harvest management in North America, for all its success, historically has had several shortcomings, including a lack of well-defined objectives, a failure to account for uncertain management outcomes, and inefficient use of harvest regulations to understand the effects of management. To address these and other concerns, the U.S. Fish and Wildlife Service began implementation of adaptive harvest management in 1995. Harvest policies are now developed using a Markov decision process in which there is an explicit accounting for uncontrolled environmental variation, partial controllability of harvest, and structural uncertainty in waterfowl population dynamics. Current policies are passively adaptive, in the sense that any reduction in structural uncertainty is an unplanned by-product of the regulatory process. A generalization of the Markov decision process permits the calculation of optimal actively adaptive policies, but it is not yet clear how state-specific harvest actions differ between passive and active approaches. The Markov decision process also provides managers the ability to explore optimal levels of aggregation or "management scale" for regulating harvests in a system that exhibits high temporal, spatial, and organizational variability. Progress in institutionalizing adaptive harvest management has been remarkable, but some managers still perceive the process as a panacea, while failing to appreciate the challenges presented by this more explicit and methodical approach to harvest regulation. Technical hurdles include the need to develop better linkages between population processes and the dynamics of landscapes, and to model the dynamics of structural uncertainty in a more comprehensive fashion. From an institutional perspective, agreement on how to value and allocate harvests continues to be elusive, and there is some evidence that waterfowl managers have overestimated the importance of achievement-oriented factors in setting hunting regulations. Indeed, it is these unresolved value judgements, and the lack of an effective structure for organizing debate, that present the greatest threat to adaptive harvest management as a viable means for coping with management uncertainty. Copyright ?? 1999 by The Resilience Alliance.

Low Necroptosis Process Predicts Poor Treatment Outcome of Human Papillomavirus Positive Cervical Cancers by Decreasing Tumor-Associated Macrophages M1 Polarization.

PubMed

Li, Lin; Yu, Song; Zang, Chunyi

2018-01-01

The aim of this study was to assess the functions of the necroptosis process on the prognosis of high-risk human papillomavirus (HR-HPV)-related cervical cancer. PCR and western blotting were used to demonstrate the expression of the necroptosis marker, mixed lineage kinase domain-like protein (MLKL), in whole blood and peripheral blood mononuclears (PBMCs) of 89 cervical cancer patients and 15 healthy volunteers. Necroptosis levels and M1 polarization were determined in tumor co-cultured macrophages. We found that MLKL expressions were significantly increased in cervical cancer patients in both whole blood and PBMC samples compared to the expressions in the healthy controls. Low MLKL expression was significantly associated with decreased survival rate in overall survival and disease-free survival. Co-culture cervical cancer cells decrease the necroptosis process of macrophage, together with the proinflammatory factors (M1 markers) downregulation, and this negative regulation was exacerbated in HPV-positive cases. Necroptosis enhancer RIPK3 overexpression showed reversed regulation of these M1 markers, suggesting that co-culture cervical cancer cells decrease the macrophage M1 polarization partly through necroptosis downregulation. Our study revealed that necroptosis process could be a relevant marker for the determination of the prognosis in cervical cancer patients, which might be because of its role in regulating macrophage polarization. © 2018 S. Karger AG, Basel.

Social regulation of emotion: messy layers

PubMed Central

Kappas, Arvid

2013-01-01

Emotions are evolved systems of intra- and interpersonal processes that are regulatory in nature, dealing mostly with issues of personal or social concern. They regulate social interaction and in extension, the social sphere. In turn, processes in the social sphere regulate emotions of individuals and groups. In other words, intrapersonal processes project in the interpersonal space, and inversely, interpersonal experiences deeply influence intrapersonal processes. Thus, I argue that the concepts of emotion generation and regulation should not be artificially separated. Similarly, interpersonal emotions should not be reduced to interacting systems of intraindividual processes. Instead, we can consider emotions at different social levels, ranging from dyads to large scale e-communities. The interaction between these levels is complex and does not only involve influences from one level to the next. In this sense the levels of emotion/regulation are messy and a challenge for empirical study. In this article, I discuss the concepts of emotions and regulation at different intra- and interpersonal levels. I extend the concept of auto-regulation of emotions (Kappas, 2008, 2011a,b) to social processes. Furthermore, I argue for the necessity of including mediated communication, particularly in cyberspace in contemporary models of emotion/regulation. Lastly, I suggest the use of concepts from systems dynamics and complex systems to tackle the challenge of the “messy layers.” PMID:23424049

Self-Regulation Principles Underlying Risk Perception and Decision Making within the Context of Genomic Testing

PubMed Central

Cameron, Linda D.; Biesecker, Barbara Bowles; Peters, Ellen; Taber, Jennifer M.; Klein, William M. P.

2017-01-01

Advances in theory and research on self-regulation and decision-making processes have yielded important insights into how cognitive, emotional, and social processes shape risk perceptions and risk-related decisions. We examine how self-regulation theory can be applied to inform our understanding of decision-making processes within the context of genomic testing, a clinical arena in which individuals face complex risk information and potentially life-altering decisions. After presenting key principles of self-regulation, we present a genomic testing case example to illustrate how principles related to risk representations, approach and avoidance motivations, emotion regulation, defensive responses, temporal construals, and capacities such as numeric abilities can shape decisions and psychological responses during the genomic testing process. We conclude with implications for using self-regulation theory to advance science within genomic testing and opportunities for how this research can inform further developments in self-regulation theory. PMID:29225669

Self-Regulation Principles Underlying Risk Perception and Decision Making within the Context of Genomic Testing.

PubMed

Cameron, Linda D; Biesecker, Barbara Bowles; Peters, Ellen; Taber, Jennifer M; Klein, William M P

2017-05-01

Advances in theory and research on self-regulation and decision-making processes have yielded important insights into how cognitive, emotional, and social processes shape risk perceptions and risk-related decisions. We examine how self-regulation theory can be applied to inform our understanding of decision-making processes within the context of genomic testing, a clinical arena in which individuals face complex risk information and potentially life-altering decisions. After presenting key principles of self-regulation, we present a genomic testing case example to illustrate how principles related to risk representations, approach and avoidance motivations, emotion regulation, defensive responses, temporal construals, and capacities such as numeric abilities can shape decisions and psychological responses during the genomic testing process. We conclude with implications for using self-regulation theory to advance science within genomic testing and opportunities for how this research can inform further developments in self-regulation theory.

Seasonal differences in the testicular transcriptome profile of free-living European beavers (Castor fiber L.) determined by the RNA-Seq method

PubMed Central

Paukszto, Łukasz; Jastrzębski, Jan P.; Czerwińska, Joanna; Chojnowska, Katarzyna; Kamińska, Barbara; Kurzyńska, Aleksandra; Smolińska, Nina; Giżejewski, Zygmunt; Kamiński, Tadeusz

2017-01-01

The European beaver (Castor fiber L.) is an important free-living rodent that inhabits Eurasian temperate forests. Beavers are often referred to as ecosystem engineers because they create or change existing habitats, enhance biodiversity and prepare the environment for diverse plant and animal species. Beavers are protected in most European Union countries, but their genomic background remains unknown. In this study, gene expression patterns in beaver testes and the variations in genetic expression in breeding and non-breeding seasons were determined by high-throughput transcriptome sequencing. Paired-end sequencing in the Illumina HiSeq 2000 sequencer produced a total of 373.06 million of high-quality reads. De novo assembly of contigs yielded 130,741 unigenes with an average length of 1,369.3 nt, N50 value of 1,734, and average GC content of 46.51%. A comprehensive analysis of the testicular transcriptome revealed more than 26,000 highly expressed unigenes which exhibited the highest homology with Rattus norvegicus and Ictidomys tridecemlineatus genomes. More than 8,000 highly expressed genes were found to be involved in fundamental biological processes, cellular components or molecular pathways. The study also revealed 42 genes whose regulation differed between breeding and non-breeding seasons. During the non-breeding period, the expression of 37 genes was up-regulated, and the expression of 5 genes was down-regulated relative to the breeding season. The identified genes encode molecules which are involved in signaling transduction, DNA repair, stress responses, inflammatory processes, metabolism and steroidogenesis. Our results pave the way for further research into season-dependent variations in beaver testes. PMID:28678806

Dynamic regulation of hepatic lipid droplet properties by diet.

PubMed

Crunk, Amanda E; Monks, Jenifer; Murakami, Aya; Jackman, Matthew; Maclean, Paul S; Ladinsky, Mark; Bales, Elise S; Cain, Shannon; Orlicky, David J; McManaman, James L

2013-01-01

Cytoplasmic lipid droplets (CLD) are organelle-like structures that function in neutral lipid storage, transport and metabolism through the actions of specific surface-associated proteins. Although diet and metabolism influence hepatic CLD levels, how they affect CLD protein composition is largely unknown. We used non-biased, shotgun, proteomics in combination with metabolic analysis, quantitative immunoblotting, electron microscopy and confocal imaging to define the effects of low- and high-fat diets on CLD properties in fasted-refed mice. We found that the hepatic CLD proteome is distinct from that of CLD from other mammalian tissues, containing enzymes from multiple metabolic pathways. The hepatic CLD proteome is also differentially affected by dietary fat content and hepatic metabolic status. High fat feeding markedly increased the CLD surface density of perilipin-2, a critical regulator of hepatic neutral lipid storage, whereas it reduced CLD levels of betaine-homocysteine S-methyltransferase, an enzyme regulator of homocysteine levels linked to fatty liver disease and hepatocellular carcinoma. Collectively our data demonstrate that the hepatic CLD proteome is enriched in metabolic enzymes, and that it is qualitatively and quantitatively regulated by diet and metabolism. These findings implicate CLD in the regulation of hepatic metabolic processes, and suggest that their properties undergo reorganization in response to hepatic metabolic demands.

Dynamic Regulation of Hepatic Lipid Droplet Properties by Diet

PubMed Central

Crunk, Amanda E.; Monks, Jenifer; Murakami, Aya; Jackman, Matthew; MacLean, Paul S.; Ladinsky, Mark; Bales, Elise S.; Cain, Shannon; Orlicky, David J.; McManaman, James L.

2013-01-01

Cytoplasmic lipid droplets (CLD) are organelle-like structures that function in neutral lipid storage, transport and metabolism through the actions of specific surface-associated proteins. Although diet and metabolism influence hepatic CLD levels, how they affect CLD protein composition is largely unknown. We used non-biased, shotgun, proteomics in combination with metabolic analysis, quantitative immunoblotting, electron microscopy and confocal imaging to define the effects of low- and high-fat diets on CLD properties in fasted-refed mice. We found that the hepatic CLD proteome is distinct from that of CLD from other mammalian tissues, containing enzymes from multiple metabolic pathways. The hepatic CLD proteome is also differentially affected by dietary fat content and hepatic metabolic status. High fat feeding markedly increased the CLD surface density of perilipin-2, a critical regulator of hepatic neutral lipid storage, whereas it reduced CLD levels of betaine-homocysteine S-methyltransferase, an enzyme regulator of homocysteine levels linked to fatty liver disease and hepatocellular carcinoma. Collectively our data demonstrate that the hepatic CLD proteome is enriched in metabolic enzymes, and that it is qualitatively and quantitatively regulated by diet and metabolism. These findings implicate CLD in the regulation of hepatic metabolic processes, and suggest that their properties undergo reorganization in response to hepatic metabolic demands. PMID:23874434

Differentially abundant proteins associated with heterosis in the primary roots of popcorn.

PubMed

Rockenbach, Mathias F; Corrêa, Caio C G; Heringer, Angelo S; Freitas, Ismael L J; Santa-Catarina, Claudete; do Amaral-Júnior, Antônio T; Silveira, Vanildo

2018-01-01

Although heterosis has significantly contributed to increases in worldwide crop production, the molecular mechanisms regulating this phenomenon are still unknown. In the present study, we used a comparative proteomic approach to explore hybrid vigor via the proteome of both the popcorn L54 ♀ and P8 ♂ genotypes and the resultant UENF/UEM01 hybrid cross. To analyze the differentially abundant proteins involved in heterosis, we used the primary roots of these genotypes to analyze growth parameters and extract proteins. The results of the growth parameter analysis showed that the mid- and best-parent heterosis were positive for root length and root dry matter but negative for root fresh matter, seedling fresh matter, and protein content. The comparative proteomic analysis identified 1343 proteins in the primary roots of hybrid UENF/UEM01 and its parental lines; 220 proteins were differentially regulated in terms of protein abundance. The mass spectrometry proteomic data are available via ProteomeXchange with identifier "PXD009436". A total of 62 regulated proteins were classified as nonadditive, of which 53.2% were classified as high parent abundance (+), 17.8% as above-high parent abundance (+ +), 16.1% as below-low parent abundance (- -), and 12.9% as low parent abundance (-). A total of 22 biological processes were associated with nonadditive proteins; processes involving translation, ribosome biogenesis, and energy-related metabolism represented 45.2% of the nonadditive proteins. Our results suggest that heterosis in the popcorn hybrid UENF/UEM01 at an early stage of plant development is associated with an up-regulation of proteins related to synthesis and energy metabolism.

Trace-Based Microanalytic Measurement of Self-Regulated Learning Processes

ERIC Educational Resources Information Center

Siadaty, Melody; Gaševic, Dragan; Hatala, Marek

2016-01-01

To keep pace with today's rapidly growing knowledge-driven society, productive self-regulation of one's learning processes are essential. We introduce and discuss a trace-based measurement protocol to measure the effects of scaffolding interventions on self-regulated learning (SRL) processes. It guides tracing of learners' actions in a learning…

15 CFR 971.210 - Determination whether application is complete for further processing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... complete for further processing. 971.210 Section 971.210 Commerce and Foreign Trade Regulations Relating to... COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR... for further processing. Upon receipt of an application, the Administrator will review it to determine...

Patterns in clinical students' self-regulated learning behavior: a Q-methodology study.

PubMed

Berkhout, Joris J; Teunissen, Pim W; Helmich, Esther; van Exel, Job; van der Vleuten, Cees P M; Jaarsma, Debbie A D C

2017-03-01

Students feel insufficiently supported in clinical environments to engage in active learning and achieve a high level of self-regulation. As a result clinical learning is highly demanding for students. Because of large differences between students, supervisors may not know how to support them in their learning process. We explored patterns in undergraduate students' self-regulated learning behavior in the clinical environment, to improve tailored supervision, using Q-methodology. Q-methodology uses features of both qualitative and quantitative methods for the systematic investigation of subjective issues by having participants sort statements along a continuum to represent their opinion. We enrolled 74 students between December 2014 and April 2015 and had them characterize their learning behavior by sorting 52 statements about self-regulated learning behavior and explaining their response. The statements used for the sorting were extracted from a previous study. The data was analyzed using by-person factor analysis to identify clusters of individuals with similar sorts of the statements. The resulting factors and qualitative data were used to interpret and describe the patterns that emerged. Five resulting patterns were identified in students' self-regulated learning behavior in the clinical environment, which we labelled: Engaged, Critically opportunistic, Uncertain, Restrained and Effortful. The five patterns varied mostly regarding goals, metacognition, communication, effort, and dependence on external regulation for learning. These discrete patterns in students' self-regulated learning behavior in the clinical environment are part of a complex interaction between student and learning context. The results suggest that developing self-regulated learning behavior might best be supported regarding individual students' needs.

Role of Melatonin in the Regulation of Differentiation of T Cells Producing Interleukin-17 (Th17).

PubMed

Kuklina, E M; Glebezdina, N S; Nekrasova, I V

2016-03-01

We studied the ability of melatonin in physiological and pharmacological concentrations to induce and/or regulate differentiation of T cells producing IL-17 (Th17). This hormone produced the opposite effect on CD4+T cells, which depended on their activation status. Melatonin induced the synthesis of IL-17A by intact T cells, but had little effect on activated cells. Melatonin in high (pharmacological) concentration decreased the intracellular expression of this cytokine under conditions of polyclonal activation. Melatonin had a dose-depended effect. Taking into the fact that Th17 cells play an important role in the immune defense, it can be suggested that the regulation of their activity by melatonin contributes to this process.

Environmental, health, and safety issues of sodium-sulfur batteries for electric and hybrid vehicles. Volume 2, Battery recycling and disposal

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

Corbus, D

1992-09-01

Recycling and disposal of spent sodium-sulfur (Na/S) batteries are important issues that must be addressed as part of the commercialization process of Na/S battery-powered electric vehicles. The use of Na/S batteries in electric vehicles will result in significant environmental benefits, and the disposal of spent batteries should not detract from those benefits. In the United States, waste disposal is regulated under the Resource Conservation and Recovery Act (RCRA). Understanding these regulations will help in selecting recycling and disposal processes for Na/S batteries that are environmentally acceptable and cost effective. Treatment processes for spent Na/S battery wastes are in the beginningmore » stages of development, so a final evaluation of the impact of RCRA regulations on these treatment processes is not possible. The objectives of tills report on battery recycling and disposal are as follows: Provide an overview of RCRA regulations and requirements as they apply to Na/S battery recycling and disposal so that battery developers can understand what is required of them to comply with these regulations; Analyze existing RCRA regulations for recycling and disposal and anticipated trends in these regulations and perform a preliminary regulatory analysis for potential battery disposal and recycling processes. This report assumes that long-term Na/S battery disposal processes will be capable of handling large quantities of spent batteries. The term disposal includes treatment processes that may incorporate recycling of battery constituents. The environmental regulations analyzed in this report are limited to US regulations. This report gives an overview of RCRA and discusses RCRA regulations governing Na/S battery disposal and a preliminary regulatory analysis for Na/S battery disposal.« less

The Social Regulation of Emotion: An Integrative, Cross-Disciplinary Model.

PubMed

Reeck, Crystal; Ames, Daniel R; Ochsner, Kevin N

2016-01-01

Research in emotion regulation has largely focused on how people manage their own emotions, but there is a growing recognition that the ways in which we regulate the emotions of others also are important. Drawing on work from diverse disciplines, we propose an integrative model of the psychological and neural processes supporting the social regulation of emotion. This organizing framework, the 'social regulatory cycle', specifies at multiple levels of description the act of regulating another person's emotions as well as the experience of being a target of regulation. The cycle describes the processing stages that lead regulators to attempt to change the emotions of a target person, the impact of regulation on the processes that generate emotions in the target, and the underlying neural systems. Copyright © 2015. Published by Elsevier Ltd.

The Social Regulation of Emotion: An Integrative, Cross-Disciplinary Model

PubMed Central

Reeck, Crystal; Ames, Daniel R.; Ochsner, Kevin N.

2018-01-01

Research in emotion regulation has largely focused on how people manage their own emotions, but there is a growing recognition that the ways in which we regulate the emotions of others also are important. Drawing on work from diverse disciplines, we propose an integrative model of the psychological and neural processes supporting the social regulation of emotion. This organizing framework, the ‘social regulatory cycle’, specifies at multiple levels of description the act of regulating another person’s emotions as well as the experience of being a target of regulation. The cycle describes the processing stages that lead regulators to attempt to change the emotions of a target person, the impact of regulation on the processes that generate emotions in the target, and the underlying neural systems. PMID:26564248

A Comparative Analysis of Industrial Escherichia coli K–12 and B Strains in High-Glucose Batch Cultivations on Process-, Transcriptome- and Proteome Level

PubMed Central

Marisch, Karoline; Bayer, Karl; Scharl, Theresa; Mairhofer, Juergen; Krempl, Peter M.; Hummel, Karin; Razzazi-Fazeli, Ebrahim; Striedner, Gerald

2013-01-01

Escherichia coli K–12 and B strains are among the most frequently used bacterial hosts for production of recombinant proteins on an industrial scale. To improve existing processes and to accelerate bioprocess development, we performed a detailed host analysis. We investigated the different behaviors of the E. coli production strains BL21, RV308, and HMS174 in response to high-glucose concentrations. Tightly controlled cultivations were conducted under defined environmental conditions for the in-depth analysis of physiological behavior. In addition to acquisition of standard process parameters, we also used DNA microarray analysis and differential gel electrophoresis (EttanTM DIGE). Batch cultivations showed different yields of the distinct strains for cell dry mass and growth rate, which were highest for BL21. In addition, production of acetate, triggered by excess glucose supply, was much higher for the K–12 strains compared to the B strain. Analysis of transcriptome data showed significant alteration in 347 of 3882 genes common among all three hosts. These differentially expressed genes included, for example, those involved in transport, iron acquisition, and motility. The investigation of proteome patterns additionally revealed a high number of differentially expressed proteins among the investigated hosts. The subsequently selected 38 spots included proteins involved in transport and motility. The results of this comprehensive analysis delivered a full genomic picture of the three investigated strains. Differentially expressed groups for targeted host modification were identified like glucose transport or iron acquisition, enabling potential optimization of strains to improve yield and process quality. Dissimilar growth profiles of the strains confirm different genotypes. Furthermore, distinct transcriptome patterns support differential regulation at the genome level. The identified proteins showed high agreement with the transcriptome data and suggest similar regulation within a host at both levels for the identified groups. Such host attributes need to be considered in future process design and operation. PMID:23950949

A comparative analysis of industrial Escherichia coli K-12 and B strains in high-glucose batch cultivations on process-, transcriptome- and proteome level.

PubMed

Marisch, Karoline; Bayer, Karl; Scharl, Theresa; Mairhofer, Juergen; Krempl, Peter M; Hummel, Karin; Razzazi-Fazeli, Ebrahim; Striedner, Gerald

2013-01-01

Escherichia coli K-12 and B strains are among the most frequently used bacterial hosts for production of recombinant proteins on an industrial scale. To improve existing processes and to accelerate bioprocess development, we performed a detailed host analysis. We investigated the different behaviors of the E. coli production strains BL21, RV308, and HMS174 in response to high-glucose concentrations. Tightly controlled cultivations were conducted under defined environmental conditions for the in-depth analysis of physiological behavior. In addition to acquisition of standard process parameters, we also used DNA microarray analysis and differential gel electrophoresis (Ettan(TM) DIGE). Batch cultivations showed different yields of the distinct strains for cell dry mass and growth rate, which were highest for BL21. In addition, production of acetate, triggered by excess glucose supply, was much higher for the K-12 strains compared to the B strain. Analysis of transcriptome data showed significant alteration in 347 of 3882 genes common among all three hosts. These differentially expressed genes included, for example, those involved in transport, iron acquisition, and motility. The investigation of proteome patterns additionally revealed a high number of differentially expressed proteins among the investigated hosts. The subsequently selected 38 spots included proteins involved in transport and motility. The results of this comprehensive analysis delivered a full genomic picture of the three investigated strains. Differentially expressed groups for targeted host modification were identified like glucose transport or iron acquisition, enabling potential optimization of strains to improve yield and process quality. Dissimilar growth profiles of the strains confirm different genotypes. Furthermore, distinct transcriptome patterns support differential regulation at the genome level. The identified proteins showed high agreement with the transcriptome data and suggest similar regulation within a host at both levels for the identified groups. Such host attributes need to be considered in future process design and operation.

Global Picture of Protein Regulation in Response to Dibutyl Phthalate (DBP) Stress of Two Brassica parachinensis Cultivars Differing in DBP Accumulation.

PubMed

Zhao, Hai-Ming; Huang, He-Biao; Du, Huan; Xiang, Lei; Mo, Ce-Hui; Li, Yan-Wen; Cai, Quan-Ying; Li, Hui; Liu, Jie-Sheng; Zhou, Dong-Mei; Wong, Ming-Hung

2018-05-09

iTRAQ analysis was used to map the proteomes of two Brassica parachinensis cultivars that differed in dibutyl phthalate (DBP) accumulation. A total of 5699 proteins were identified to obtain 152 differentially regulated proteins, of which 64 and 48 were specific to a high- and a low-DBP-accumulation cultivar, respectively. Genotype-specific biological processes were involved in coping with DBP stress, accounting for the variation in DBP tolerance and accumulation. Formation of high DBP accumulation in B. parachinensis might attribute to the more effective regulation of protein expression in physiology and metabolism, including (a) enhanced cell wall biosynthesis and modification, (b) better maintenance of photosynthesis and energy balance, (c) greatly improved total capacity for antioxidation and detoxification, and (d) enhanced cellular transport and signal transduction. Our novel findings contribute to a global picture of DBP-induced alterations of protein profiles in crops and provide valuable information for the development of molecular-assisted breeds of low-accumulation cultivars.

Taotie neurons regulate appetite in Drosophila

PubMed Central

Zhan, Yin Peng; Liu, Li; Zhu, Yan

2016-01-01

The brain has an essential role in maintaining a balance between energy intake and expenditure of the body. Deciphering the processes underlying the decision-making for timely feeding of appropriate amounts may improve our understanding of physiological and psychological disorders related to feeding control. Here, we identify a group of appetite-enhancing neurons in a behavioural screen for flies with increased appetite. Manipulating the activity of these neurons, which we name Taotie neurons, induces bidirectional changes in feeding motivation. Long-term stimulation of Taotie neurons results in flies with highly obese phenotypes. Furthermore, we show that the in vivo activity of Taotie neurons in the neuroendocrine region reflects the hunger/satiety states of un-manipulated animals, and that appetitive-enhancing Taotie neurons control the secretion of insulin, a known regulator of feeding behaviour. Thus, our study reveals a new set of neurons regulating feeding behaviour in the high brain regions that represents physiological hunger states and control feeding behaviour in Drosophila. PMID:27924813

Development of Novel Antisense Oligonucleotides for the Functional Regulation of RNA-Induced Silencing Complex (RISC) by Promoting the Release of microRNA from RISC.

PubMed

Ariyoshi, Jumpei; Momokawa, Daiki; Eimori, Nao; Kobori, Akio; Murakami, Akira; Yamayoshi, Asako

2015-12-16

MicroRNAs (miRNAs) are known to be important post-transcription regulators of gene expression. Aberrant miRNA expression is associated with pathological disease processes, including carcinogenesis. Therefore, miRNAs are considered significant therapeutic targets for cancer therapy. MiRNAs do not act alone, but exhibit their functions by forming RNA-induced silencing complex (RISC). Thus, the regulation of RISC activity is a promising approach for cancer therapy. MiRNA is a core component of RISC and is an essential to RISC for recognizing target mRNA. Thereby, it is expected that development of the method to promote the release of miRNA from RISC would be an effective approach for inhibition of RISC activity. In this study, we synthesized novel peptide-conjugated oligonucleotides (RINDA-as) to promote the release of miRNA from RISC. RINDA-as showed a high rate of miRNA release from RISC and high level of inhibitory effect on RISC activity.

Computation of records of streamflow at control structures

USGS Publications Warehouse

Collins, Dannie L.

1977-01-01

Traditional methods of computing streamflow records on large, low-gradient streams require a continuous record of water-surface slope over a natural channel reach. This slope must be of sufficient magnitude to be accuratly measured with available stage measuring devices. On highly regulated streams, this slope approaches zero during periods of low flow and accurate measurement is difficult. Methods are described to calibrate multipurpose regulating control structures to more accurately compute streamflow records on highly-regulated streams. Hydraulic theory, assuming steady, uniform flow during a computational interval, is described for five different types of flow control. The controls are: Tainter gates, hydraulic turbines, fixed spillways, navigation locks, and crest gates. Detailed calibration procedures are described for the five different controls as well as for several flow regimes for some of the controls. The instrumentation package and computer programs necessary to collect and process the field data are discussed. Two typical calibration procedures and measurement data are presented to illustrate the accuracy of the methods. (Woodard-USGS)

Gene expression profiling reveals two separate mechanisms regulating apoptosis in rectal carcinomas in vivo

PubMed Central

de Bruin, Elza C.; van de Pas, Simone; van de Velde, Cornelis J. H.; van Krieken, J. Han J. M.; Peltenburg, Lucy T. C.; Marijnen, Corrie A. M.

2007-01-01

The level of apoptosis in rectal carcinomas of patients treated by surgery only predicts local failure; patients with intrinsically high-apoptotic tumors develop less local recurrences than patients with low levels of apoptosis. To identify genes involved in this intrinsic apoptotic process in vivo, 47 rectal tumors with known apoptotic phenotype (24 low- and 23 high-apoptotic) were analyzed by oligonucleotide microarray technology. We identified several genes differentially expressed between low- and high-apoptotic tumors. Unsupervised clustering of the tumors based on expression levels of these genes separated the low-apoptotic from the high-apoptotic tumors, indicating a gene expression-dependent regulation. In addition, this clustering revealed two subgroups of high-apoptotic tumors. One high-apoptotic subgroup showed subtle differences in mRNA and protein expression of the known apoptotic regulators BAX, cIAP2 and ARC compared to the low-apoptotic tumors. The other subgroup of high-apoptotic tumors showed high expression of immune-related genes; predominantly HLA class II and chemokines, but also HLA class I and interferon-inducible genes were highly expressed. Immunohistochemistry revealed HLA-DR expression in epithelial tumor cells in 70% of these high-apoptotic tumors. The expression data suggest that high levels of apoptosis in rectal carcinoma patients can be the result of either slightly altered expression of known pro- and anti-apoptotic genes or high expression of immune-related genes. Electronic supplementary material The online version of this article (doi: 10.1007/s10495-007-0088-2) contains supplementary material, which is available to authorized users. PMID:17610066

An integrated water system model considering hydrological and biogeochemical processes at basin scale: model construction and application

NASA Astrophysics Data System (ADS)

Zhang, Y. Y.; Shao, Q. X.; Ye, A. Z.; Xing, H. T.

2014-08-01

Integrated water system modeling is a reasonable approach to provide scientific understanding and possible solutions to tackle the severe water crisis faced over the world and to promote the implementation of integrated river basin management. Such a modeling practice becomes more feasible nowadays due to better computing facilities and available data sources. In this study, the process-oriented water system model (HEXM) is developed by integrating multiple water related processes including hydrology, biogeochemistry, environment and ecology, as well as the interference of human activities. The model was tested in the Shaying River Catchment, the largest, highly regulated and heavily polluted tributary of Huai River Basin in China. The results show that: HEXM is well integrated with good performance on the key water related components in the complex catchments. The simulated daily runoff series at all the regulated and less-regulated stations matches observations, especially for the high and low flow events. The average values of correlation coefficient and coefficient of efficiency are 0.81 and 0.63, respectively. The dynamics of observed daily ammonia-nitrogen (NH4N) concentration, as an important index to assess water environmental quality in China, are well captured with average correlation coefficient of 0.66. Furthermore, the spatial patterns of nonpoint source pollutant load and grain yield are also simulated properly, and the outputs have good agreements with the statistics at city scale. Our model shows clear superior performance in both calibration and validation in comparison with the widely used SWAT model. This model is expected to give a strong reference for water system modeling in complex basins, and provide the scientific foundation for the implementation of integrated river basin management all over the world as well as the technical guide for the reasonable regulation of dams and sluices and environmental improvement in river basins.

IRE1α prevents hepatic steatosis by processing and promoting the degradation of select microRNAs.

PubMed

Wang, Jie-Mei; Qiu, Yining; Yang, Zhao; Kim, Hyunbae; Qian, Qingwen; Sun, Qinghua; Zhang, Chunbin; Yin, Lei; Fang, Deyu; Back, Sung Hong; Kaufman, Randal J; Yang, Ling; Zhang, Kezhong

2018-05-15

Obesity or a high-fat diet represses the endoribonuclease activity of inositol-requiring enzyme 1α (IRE1α), a transducer of the unfolded protein response (UPR) in cells under endoplasmic reticulum (ER) stress. An impaired UPR is associated with hepatic steatosis and nonalcoholic fatty liver disease (NAFLD), which is caused by lipid accumulation in the liver. We found that IRE1α was critical to maintaining lipid homeostasis in the liver by repressing the biogenesis of microRNAs (miRNAs) that regulate lipid mobilization. In mice fed normal chow, the endoribonuclease function of IRE1α processed a subset of precursor miRNAs in the liver, including those of the miR-200 and miR-34 families, such that IRE1α promoted their degradation through the process of regulated IRE1-dependent decay (RIDD). A high-fat diet in mice or hepatic steatosis in patients was associated with the S-nitrosylation of IRE1α and inactivation of its endoribonuclease activity. This resulted in an increased abundance of these miRNA families in the liver and, consequently, a decreased abundance of their targets, which included peroxisome proliferator-activated receptor α (PPARα) and the deacetylase sirtuin 1 (SIRT1), regulators of fatty acid oxidation and triglyceride lipolysis. IRE1α deficiency exacerbated hepatic steatosis in mice. The abundance of the miR-200 and miR-34 families was also increased in cultured, lipid-overloaded hepatocytes and in the livers of patients with hepatic steatosis. Our findings reveal a mechanism by which IRE1α maintains lipid homeostasis through its regulation of miRNAs, a regulatory pathway distinct from the canonical IRE1α-UPR pathway under acute ER stress. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Processing of hemojuvelin requires retrograde trafficking to the Golgi in HepG2 cells.

PubMed

Maxson, Julia E; Enns, Caroline A; Zhang, An-Sheng

2009-02-19

Hemojuvelin (HJV) was recently identified as a critical regulator of iron homeostasis. It is either associated with cell membranes through a glycosylphosphatidylinositol anchor or released as a soluble form. Membrane-anchored HJV acts as a coreceptor for bone morphogenetic proteins and activates the transcription of hepcidin, a hormone that regulates iron efflux from cells. Soluble HJV antagonizes bone morphogenetic protein signaling and suppresses hepcidin expression. In this study, we examined the trafficking and processing of HJV. Cellular HJV reached the plasma membrane without obtaining complex oligosaccharides, indicating that HJV avoided Golgi processing. Secreted HJV, in contrast, has complex oligosaccharides and can be derived from HJV with high-mannose oligosaccharides at the plasma membrane. Our results support a model in which retrograde trafficking of HJV before cleavage is the predominant processing pathway. Release of HJV requires it to bind to the transmembrane receptor neogenin. Neogenin does not, however, play a role in HJV trafficking to the cell surface, suggesting that it could be involved either in retrograde trafficking of HJV or in cleavage leading to HJV release.

Processing of hemojuvelin requires retrograde trafficking to the Golgi in HepG2 cells

PubMed Central

Maxson, Julia E.; Enns, Caroline A.

2009-01-01

Hemojuvelin (HJV) was recently identified as a critical regulator of iron homeostasis. It is either associated with cell membranes through a glycosylphosphatidylinositol anchor or released as a soluble form. Membrane-anchored HJV acts as a coreceptor for bone morphogenetic proteins and activates the transcription of hepcidin, a hormone that regulates iron efflux from cells. Soluble HJV antagonizes bone morphogenetic protein signaling and suppresses hepcidin expression. In this study, we examined the trafficking and processing of HJV. Cellular HJV reached the plasma membrane without obtaining complex oligosaccharides, indicating that HJV avoided Golgi processing. Secreted HJV, in contrast, has complex oligosaccharides and can be derived from HJV with high-mannose oligosaccharides at the plasma membrane. Our results support a model in which retrograde trafficking of HJV before cleavage is the predominant processing pathway. Release of HJV requires it to bind to the transmembrane receptor neogenin. Neogenin does not, however, play a role in HJV trafficking to the cell surface, suggesting that it could be involved either in retrograde trafficking of HJV or in cleavage leading to HJV release. PMID:19029439

Transcriptome profiling and pathway analysis of hepatotoxicity induced by tris (2-ethylhexyl) trimellitate (TOTM) in mice.

PubMed

Chen, Xian-Hua; Ma, Li; Hu, Yi-Xiang; Wang, Dan-Xian; Fang, Li; Li, Xue-Lai; Zhao, Jin-Chuan; Yu, Hai-Rong; Ying, Hua-Zhong; Yu, Chen-Huan

2016-01-01

Tris (2-ethylhexyl) trimellitate (TOTM) is commonly used as an alternative plasticizer for medical devices. But very little information was available on its biological effects. In this study, we investigated toxicity effects of TOTM on hepatic differential gene expression analyzed by using high-throughput sequencing analysis for over-represented functions and phenotypically anchored to complementary histopathologic, and biochemical data in the liver of mice. Among 1668 candidate genes, 694 genes were up-regulated and 974 genes were down-regulated after TOTM exposure. Using Gene Ontology analysis, TOTM affected three processes: the cell cycle, metabolic process and oxidative activity. Furthermore, 11 key genes involved in the above processes were validated by real time PCR. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these genes were involved in the cell cycle pathway, lipid metabolism and oxidative process. It revealed the transcriptome gene expression response to TOTM exposure in mouse, and these data could contribute to provide a clearer understanding of the molecular mechanisms of TOTM-induced hepatotoxicity in human. Copyright © 2015 Elsevier B.V. All rights reserved.

Persons' various experiences of learning processes in patient education for osteoarthritis, a qualitative phenomenographic approach.

PubMed

Larsson, Ingalill; Sundén, Anne; Ekvall Hansson, Eva

2018-03-30

Patient education (PE) is a core treatment of osteoarthritis (OA) with the aim to increase persons' knowledge, self-efficacy, and empowerment. To describe person's various experiences of learning processes in PE for OA. Phenomenography. Semi-structured interviews were performed with the same persons, pre- (11) and post- (9) education. Various experiences on learning processes were found and were described in an outcome space. Achieving knowledge describes self-regulated learning and strongly relates to Control, which describes a high order cognitive learning skill, and minor to Confirm, which describes a cognitive learning skill based on recognition and application. Receiving knowledge describes the expectancy of learning regulated from the educator and strongly relates to Comply, which describes a low-order cognitive learning skill, and minor to Confirm. Different experiences of motivation and learning impact on persons' learning processes which, in turn, influence the persons' capability to accomplish self-efficacy and empowerment. The outcome space may serve as a basis for discussions between healthcare educators involved in PE to better understand what learning implies and to develop PE further.

The effects of bisphosphonates on taurine transport in retinal capillary endothelial cells under high glucose conditions.

PubMed

Lee, Na-Young; Kang, Young-Sook

2013-01-01

Diabetic retinopathy (DR) is a major cause of blindness in diabetic patients. Elevated glucose and vascular endothelial growth factor (VEGF) in retina can trigger many of the retinal vascular changes caused by diabetes and DR. Recently, bisphosphonates, antiosteoporosis drugs, have been reported to have anti-angiogenic effect by decreasing VEGF. Taurine has several biological processes such as osmoregulation and antioxidation in retina. Therefore, the purpose of this study is to clarify the regulation of taurine transport activity by high glucose concentration and the effect of inhibitors for VEGF function, bisphosphonates, on taurine transport under high glucose condition using TR-iBRB cell lines as an in vitro model of inner blood-retinal barrier (iBRB). As a result, by exposing TR-iBRB cells to high glucose for 48 h, [(3)H]taurine uptake was decreased continuously. [(3)H]Taurine uptake was increased significantly by pretreatment of alendronate and pamidronate compared with the values for high glucose. Increased [(3)H]taurine uptake by pretreatment of alendronate and pamidronate was significantly reduced by mevalonate pathway intermediates, geranylgeraniol (GGOH). In conclusion, taurine transport through the iBRB under high glucose condition can be regulated by bisphosphonates via mevalonate pathway. Therefore, we suggest that bisphosphonates could have the beneficial effects on DR by regulation of taurine contents in retina.

Expert Voices in Learning Improvisation: Shaping Regulation Processes through Experiential Influence

ERIC Educational Resources Information Center

de Bruin, Leon R.

2017-01-01

Interpersonal and collaborative activity plays an important role in the social aspects of self-regulated learning (SRL) development. Peer, teacher and group interactions facilitate support for self-regulation, co-regulation and socially shared regulatory processes. Situated and experiential interplay facilitates personal, co-constructed and…

Central genes, pathways and modules that regulate bone mass.

PubMed

Quiros-Gonzalez, Isabel; Yadav, Vijay K

2014-11-01

Bones are structures that give the shape and defined features to vertebrates, protect several soft organs and perform multiple endocrine influences on other organs. To achieve these functions bones are first modeled early during life and then constantly remodeled throughout life. The process of bone (re)modeling happens simultaneously at multitude of locations in the skeleton and ensures that vertebrates have a mechanically strong yet a flexible skeleton to the most part of their life. Given the extent of its occurrence in the body, bone remodeling is a highly energy demanding process and is co-ordinated with other physiological processes as diverse as energy metabolism, sleep-wake cycle and reproduction. Neuronal circuits in the brain play a very important role in the coordination of bone remodeling with other organ system functions, and perform this function in sync with environmental and peripheral hormonal cues. In this review, we will focus on the roles of hormonal signals and neural circuits that originate in, or impinge on, the brain in the regulation of bone mass. We will provide herein an updated view of how advances in molecular genetics have refined the neural circuits involved in the regulation of bone mass, from the whole brain level to the specific neuronal populations and their neurotransmitters. This will help to understand the mechanisms whereby vertebrate brain regulates bone mass by fine-tuning metabolic signals that originate in the brain or elsewhere in the body. Copyright © 2014 Elsevier Inc. All rights reserved.

The Arabidopsis MYB96 Transcription Factor Is a Positive Regulator of ABSCISIC ACID-INSENSITIVE4 in the Control of Seed Germination1

PubMed Central

Lee, Kyounghee; Lee, Hong Gil; Kim, Hyun Uk; Seo, Pil Joon

2015-01-01

Seed germination is a key developmental transition that initiates the plant life cycle. The timing of germination is determined by the coordinated action of two phytohormones, gibberellin and abscisic acid (ABA). In particular, ABA plays a key role in integrating environmental information and inhibiting the germination process. The utilization of embryonic lipid reserves contributes to seed germination by acting as an energy source, and ABA suppresses lipid degradation to modulate the germination process. Here, we report that the ABA-responsive R2R3-type MYB transcription factor MYB96, which is highly expressed in embryo, regulates seed germination by controlling the expression of ABSCISIC ACID-INSENSITIVE4 (ABI4) in Arabidopsis (Arabidopsis thaliana). In the presence of ABA, germination was accelerated in MYB96-deficient myb96-1 seeds, whereas the process was significantly delayed in MYB96-overexpressing activation-tagging myb96-ox seeds. Consistently, myb96-1 seeds degraded a larger extent of lipid reserves even in the presence of ABA, while reduced lipid mobilization was observed in myb96-ox seeds. MYB96 directly regulates ABI4, which acts as a repressor of lipid breakdown, to define its spatial and temporal expression. Genetic analysis further demonstrated that ABI4 is epistatic to MYB96 in the control of seed germination. Taken together, the MYB96-ABI4 module regulates lipid mobilization specifically in the embryo to ensure proper seed germination under suboptimal conditions. PMID:25869652

Transcriptome analysis of a spontaneous mutant in sweet orange [Citrus sinensis (L.) Osbeck] during fruit development.

PubMed

Liu, Qing; Zhu, Andan; Chai, Lijun; Zhou, Wenjing; Yu, Keqin; Ding, Jian; Xu, Juan; Deng, Xiuxin

2009-01-01

Bud mutations often arise in citrus. The selection of mutants is one of the most important breeding channels in citrus. However, the molecular basis of bud mutation has rarely been studied. To identify differentially expressed genes in a spontaneous sweet orange [C. sinensis (L.) Osbeck] bud mutation which causes lycopene accumulation, low citric acid, and high sucrose in fruit, suppression subtractive hybridization and microarray analysis were performed to decipher this bud mutation during fruit development. After sequencing of the differentially expressed clones, a total of 267 non-redundant transcripts were obtained and 182 (68.2%) of them shared homology (E-value < or = 1x10(-10)) with known gene products. Few genes were constitutively up- or down-regulated (fold change > or = 2) in the bud mutation during fruit development. Self-organizing tree algorithm analysis results showed that 95.1% of the differentially expressed genes were extensively coordinated with the initiation of lycopene accumulation. Metabolic process, cellular process, establishment of localization, response to stimulus, and biological regulation-related transcripts were among the most regulated genes. These genes were involved in many biological processes such as organic acid metabolism, lipid metabolism, transport, and pyruvate metabolism, etc. Moreover, 13 genes which were differentially regulated at 170 d after flowering shared homology with previously described signal transduction or transcription factors. The information generated in this study provides new clues to aid in the understanding of bud mutation in citrus.

Rac Regulates Giardia lamblia Encystation by Coordinating Cyst Wall Protein Trafficking and Secretion.

PubMed

Krtková, Jana; Thomas, Elizabeth B; Alas, Germain C M; Schraner, Elisabeth M; Behjatnia, Habib R; Hehl, Adrian B; Paredez, Alexander R

2016-08-23

Encystation of the common intestinal parasite Giardia lamblia involves the production, trafficking, and secretion of cyst wall material (CWM). However, the molecular mechanism responsible for the regulation of these sequential processes remains elusive. Here, we examined the role of GlRac, Giardia's sole Rho family GTPase, in the regulation of endomembrane organization and cyst wall protein (CWP) trafficking. Localization studies indicated that GlRac is associated with the endoplasmic reticulum (ER) and the Golgi apparatus-like encystation-specific vesicles (ESVs). Constitutive GlRac signaling increased levels of the ER marker PDI2, induced ER swelling, reduced overall CWP1 production, and promoted the early maturation of ESVs. Quantitative analysis of cells expressing constitutively active hemagglutinin (HA)-tagged GlRac (HA-Rac(CA)) revealed fewer but larger ESVs than control cells. Consistent with the phenotype of premature maturation of ESVs in HA-Rac(CA)-expressing cells, constitutive GlRac signaling resulted in increased CWP1 secretion and, conversely, morpholino depletion of GlRac blocked CWP1 secretion. Wild-type cells unexpectedly secreted large quantities of CWP1 into the medium, and free CWP1 was used cooperatively during cyst formation. These results, in part, could account for the previously reported observation that G. lamblia encysts more efficiently at high cell densities. These studies of GlRac show that it regulates encystation at several levels, and our findings support its coordinating role as a regulator of CWP trafficking and secretion. The central role of GlRac in regulating membrane trafficking and the cytoskeleton, both of which are essential to Giardia parasitism, further suggests its potential as a novel target for drug development to treat giardiasis. The encystation process is crucial for the transmission of giardiasis and the life cycle of many protists. Encystation for Giardia lamblia involves the assembly of a protective cyst wall via sequential production, trafficking, and secretion of cyst wall material. However, the regulatory pathways that coordinate cargo maturation and secretion remain unknown. Here, we asked whether the signaling activities of G. lamblia's single Rho family GTPase, GlRac, might have a regulatory role in the encystation process. We show that GlRac localizes to endomembranes and its signaling activities regulate the production of cyst wall protein 1 (CWP1), the maturation of encystation-specific vesicles (ESVs), and secretion of CWP1. We also show that secreted CWP1 is available for the development of cysts at the population level, a finding that in part could explain why Giardia encystation proceeds more efficiently at high cell densities. Copyright © 2016 Krtková et al.

The fragile X mental retardation protein regulates tumor invasiveness-related pathways in melanoma cells

PubMed Central

Zalfa, Francesca; Panasiti, Vincenzo; Carotti, Simone; Zingariello, Maria; Perrone, Giuseppe; Sancillo, Laura; Pacini, Laura; Luciani, Flavie; Roberti, Vincenzo; D'Amico, Silvia; Coppola, Rosa; Abate, Simona Osella; Rana, Rosa Alba; De Luca, Anastasia; Fiers, Mark; Melocchi, Valentina; Bianchi, Fabrizio; Farace, Maria Giulia; Achsel, Tilmann; Marine, Jean-Christophe; Morini, Sergio; Bagni, Claudia

2017-01-01

The fragile X mental retardation protein (FMRP) is lacking or mutated in patients with the fragile X syndrome (FXS), the most frequent form of inherited intellectual disability. FMRP affects metastasis formation in a mouse model for breast cancer. Here we show that FMRP is overexpressed in human melanoma with high Breslow thickness and high Clark level. Furthermore, meta-analysis of the TCGA melanoma data revealed that high levels of FMRP expression correlate significantly with metastatic tumor tissues, risk of relapsing and disease-free survival. Reduction of FMRP in metastatic melanoma cell lines impinges on cell migration, invasion and adhesion. Next-generation sequencing in human melanoma cells revealed that FMRP regulates a large number of mRNAs involved in relevant processes of melanoma progression. Our findings suggest an association between FMRP levels and the invasive phenotype in melanoma and might open new avenues towards the discovery of novel therapeutic targets. PMID:29144507

The fragile X mental retardation protein regulates tumor invasiveness-related pathways in melanoma cells.

PubMed

Zalfa, Francesca; Panasiti, Vincenzo; Carotti, Simone; Zingariello, Maria; Perrone, Giuseppe; Sancillo, Laura; Pacini, Laura; Luciani, Flavie; Roberti, Vincenzo; D'Amico, Silvia; Coppola, Rosa; Abate, Simona Osella; Rana, Rosa Alba; De Luca, Anastasia; Fiers, Mark; Melocchi, Valentina; Bianchi, Fabrizio; Farace, Maria Giulia; Achsel, Tilmann; Marine, Jean-Christophe; Morini, Sergio; Bagni, Claudia

2017-11-16

The fragile X mental retardation protein (FMRP) is lacking or mutated in patients with the fragile X syndrome (FXS), the most frequent form of inherited intellectual disability. FMRP affects metastasis formation in a mouse model for breast cancer. Here we show that FMRP is overexpressed in human melanoma with high Breslow thickness and high Clark level. Furthermore, meta-analysis of the TCGA melanoma data revealed that high levels of FMRP expression correlate significantly with metastatic tumor tissues, risk of relapsing and disease-free survival. Reduction of FMRP in metastatic melanoma cell lines impinges on cell migration, invasion and adhesion. Next-generation sequencing in human melanoma cells revealed that FMRP regulates a large number of mRNAs involved in relevant processes of melanoma progression. Our findings suggest an association between FMRP levels and the invasive phenotype in melanoma and might open new avenues towards the discovery of novel therapeutic targets.

Does Training in How to Regulate One's Learning Affect How Students Report Self-Regulated Learning in Diary Tasks?

ERIC Educational Resources Information Center

Costa Ferreira, P.; Veiga Simão, A. M.; Lopes da Silva, A.

2015-01-01

The processes and perceptions of students' self-regulated learning are not easily measured. Thus, research has presented and suggested numerous ways in which these processes and perceptions of self-regulated learning can be investigated and assessed. Accordingly, this study aims to assess whether training in how to regulate one's learning is…

Getting to the Heart of Emotion Regulation in Youth: The Role of Interoceptive Sensitivity, Heart Rate Variability, and Parental Psychopathology

PubMed Central

Sütterlin, Stefan; Braet, Caroline; Mueller, Sven C.

2016-01-01

Emotion regulation and associated autonomic activation develop throughout childhood and adolescence under the influence of the family environment. Specifically, physiological indicators of autonomic nervous system activity such as interoceptive sensitivity and vagally mediated heart rate variability (HRV) can inform on emotion regulation. Although the effect of parental emotion socialization on emotion regulation appears to be influenced by autonomic processes, research on physiological regulation and the influence of parental factors remains scarce. This study investigated the relationship between self-reported habitual emotion regulation strategies and HRV at rest as well as interoceptive sensitivity in forty-six youngsters (27 female; age: M = 13.00, SD = 2.13). Secondly, the association between these autonomic correlates and parental psychopathology was also studied. Whereas better interoceptive sensitivity was related to reduced maladaptive emotion regulation, specifically rumination, high HRV was related to more use of external emotion regulation strategies (i.e., support seeking). In addition, increased HRV and decreased interoceptive sensitivity were associated with maternal internalizing and there was evidence for a possible mediation effect of HRV in the relationship between maternal internalizing and child external emotion regulation. This study elucidates the link between cognitive emotion regulation strategies and underlying physiological regulation in adolescents but also indicates a putative influence of maternal internalizing symptoms on emotion regulation in their offspring. PMID:27741261

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

PubMed Central

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

2017-01-01

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

The Older Adult Positivity Effect in Evaluations of Trustworthiness: Emotion Regulation or Cognitive Capacity?

PubMed

Zebrowitz, Leslie A; Boshyan, Jasmine; Ward, Noreen; Gutchess, Angela; Hadjikhani, Nouchine

2017-01-01

An older adult positivity effect, i.e., the tendency for older adults to favor positive over negative stimulus information more than do younger adults, has been previously shown in attention, memory, and evaluations. This effect has been attributed to greater emotion regulation in older adults. In the case of attention and memory, this explanation has been supported by some evidence that the older adult positivity effect is most pronounced for negative stimuli, which would motivate emotion regulation, and that it is reduced by cognitive load, which would impede emotion regulation. We investigated whether greater older adult positivity in the case of evaluative responses to faces is also enhanced for negative stimuli and attenuated by cognitive load, as an emotion regulation explanation would predict. In two studies, younger and older adults rated trustworthiness of faces that varied in valence both under low and high cognitive load, with the latter manipulated by a distracting backwards counting task. In Study 1, face valence was manipulated by attractiveness (low /disfigured faces, medium, high/fashion models' faces). In Study 2, face valence was manipulated by trustworthiness (low, medium, high). Both studies revealed a significant older adult positivity effect. However, contrary to an emotion regulation account, this effect was not stronger for more negative faces, and cognitive load increased rather than decreased the rated trustworthiness of negatively valenced faces. Although inconsistent with emotion regulation, the latter effect is consistent with theory and research arguing that more cognitive resources are required to process negative stimuli, because they are more cognitively elaborated than positive ones. The finding that increased age and increased cognitive load both enhanced the positivity of trustworthy ratings suggests that the older adult positivity effect in evaluative ratings of faces may reflect age-related declines in cognitive capacity rather than increases in the regulation of negative emotions.

Examining the Evolution of the Regulatory Circuit Controlling Secondary Metabolism and Development in the Fungal Genus Aspergillus

PubMed Central

Lind, Abigail L.; Wisecaver, Jennifer H.; Smith, Timothy D.; Feng, Xuehuan; Calvo, Ana M.; Rokas, Antonis

2015-01-01

Filamentous fungi produce diverse secondary metabolites (SMs) essential to their ecology and adaptation. Although each SM is typically produced by only a handful of species, global SM production is governed by widely conserved transcriptional regulators in conjunction with other cellular processes, such as development. We examined the interplay between the taxonomic narrowness of SM distribution and the broad conservation of global regulation of SM and development in Aspergillus, a diverse fungal genus whose members produce well-known SMs such as penicillin and gliotoxin. Evolutionary analysis of the 2,124 genes comprising the 262 SM pathways in four Aspergillus species showed that most SM pathways were species-specific, that the number of SM gene orthologs was significantly lower than that of orthologs in primary metabolism, and that the few conserved SM orthologs typically belonged to non-homologous SM pathways. RNA sequencing of two master transcriptional regulators of SM and development, veA and mtfA, showed that the effects of deletion of each gene, especially veA, on SM pathway regulation were similar in A. fumigatus and A. nidulans, even though the underlying genes and pathways regulated in each species differed. In contrast, examination of the role of these two regulators in development, where 94% of the underlying genes are conserved in both species showed that whereas the role of veA is conserved, mtfA regulates development in the homothallic A. nidulans but not in the heterothallic A. fumigatus. Thus, the regulation of these highly conserved developmental genes is divergent, whereas–despite minimal conservation of target genes and pathways–the global regulation of SM production is largely conserved. We suggest that the evolution of the transcriptional regulation of secondary metabolism in Aspergillus represents a novel type of regulatory circuit rewiring and hypothesize that it has been largely driven by the dramatic turnover of the target genes involved in the process. PMID:25786130

Event-related potentials reveal preserved attention allocation but impaired emotion regulation in patients with epilepsy and comorbid negative affect.

PubMed

De Taeye, Leen; Pourtois, Gilles; Meurs, Alfred; Boon, Paul; Vonck, Kristl; Carrette, Evelien; Raedt, Robrecht

2015-01-01

Patients with epilepsy have a high prevalence of comorbid mood disorders. This study aims to evaluate whether negative affect in epilepsy is associated with dysfunction of emotion regulation. Event-related potentials (ERPs) are used in order to unravel the exact electrophysiological time course and investigate whether a possible dysfunction arises during early (attention) and/or late (regulation) stages of emotion control. Fifty epileptic patients with (n = 25) versus without (n = 25) comorbid negative affect plus twenty-five matched controls were recruited. ERPs were recorded while subjects performed a face- or house-matching task in which fearful, sad or neutral faces were presented either at attended or unattended spatial locations. Two ERP components were analyzed: the early vertex positive potential (VPP) which is normally enhanced for faces, and the late positive potential (LPP) that is typically larger for emotional stimuli. All participants had larger amplitude of the early face-sensitive VPP for attended faces compared to houses, regardless of their emotional content. By contrast, in patients with negative affect only, the amplitude of the LPP was significantly increased for unattended negative emotional expressions. These VPP results indicate that epilepsy with or without negative affect does not interfere with the early structural encoding and attention selection of faces. However, the LPP results suggest abnormal regulation processes during the processing of unattended emotional faces in patients with epilepsy and comorbid negative affect. In conclusion, this ERP study reveals that early object-based attention processes are not compromised by epilepsy, but instead, when combined with negative affect, this neurological disease is associated with dysfunction during the later stages of emotion regulation. As such, these new neurophysiological findings shed light on the complex interplay of epilepsy with negative affect during the processing of emotional visual stimuli and in turn might help to better understand the etiology and maintenance of mood disorders in epilepsy.

The healthcare off-shoring industry in developing economies--institutional and economic foundations: an Indian case.

PubMed

Kshetri, Nir

2011-01-01

Industrialized world-based healthcare providers are increasingly off-shoring low-end healthcare services such as medical transcription, billing and insurance claims. High-skill medical jobs such as tele-imaging and tele-pathology are also being sub-contracted to developing countries. Despite its importance, little theory or research exists to explain what factors affect industry growth. The article's goals, therefore, are to examine economic processes associated with developing economies' shift from low- to high-value information technology enabled healthcare services, and to investigate how these differ in terms of legitimacy from regulative, normative and cognitive institutions in the sending country and how healthcare services differ from other services. This research is conceptual and theory-building. Broadly, its approach can be described as a positivistic epistemology. Anti off-shoring regulative, normative and cognitive pressures in the sending country are likely to be stronger in healthcare than in most business process outsourcing. Moreover, such pressures are likely to be stronger in high-value rather than in low-value healthcare off-shoring. The findings also indicate that off-shoring low-value healthcare services and emergent healthcare industries in a developing economy help accumulate implicit and tacit knowledge required for off-shoring high-value healthcare services. The approach lacks primary data and empirical documentation. The article helps in understanding industry drivers and its possible future direction. The findings help in understanding the lens through which various institutional actors in a sending country view healthcare service off-shoring. The article's value stems from its analytical context, mechanisms and processes associated with developing economies' shift to high-value healthcare off-shoring services.

Epigenetic regulation of estrogen-dependent memory

PubMed Central

Fortress, Ashley M.; Frick, Karyn M.

2014-01-01

Hippocampal memory formation is highly regulated by post-translational histone modifications and DNA methylation. Accordingly, these epigenetic processes play a major role in the effects of modulatory factors, such as sex steroid hormones, on hippocampal memory. Our laboratory recently demonstrated that the ability of the potent estrogen 17β-estradiol (E2) to enhance hippocampal-dependent novel object recognition memory in ovariectomized female mice requires ERK-dependent histone H3 acetylation and DNA methylation in the dorsal hippocampus. Although these data provide valuable insight into the chromatin modifications that mediate the memory-enhancing effects of E2, epigenetic regulation of gene expression is enormously complex. Therefore, more research is needed to fully understand how E2 and other hormones employ epigenetic alterations to shape behavior. This review discusses the epigenetic alterations shown thus far to regulate hippocampal memory, briefly reviews the effects of E2 on hippocampal function, and describes in detail our work on epigenetic regulation of estrogenic memory enhancement. PMID:24878494

Epigenetic regulation of estrogen-dependent memory.

PubMed

Fortress, Ashley M; Frick, Karyn M

2014-10-01

Hippocampal memory formation is highly regulated by post-translational histone modifications and DNA methylation. Accordingly, these epigenetic processes play a major role in the effects of modulatory factors, such as sex steroid hormones, on hippocampal memory. Our laboratory recently demonstrated that the ability of the potent estrogen 17β-estradiol (E2) to enhance hippocampal-dependent novel object recognition memory in ovariectomized female mice requires ERK-dependent histone H3 acetylation and DNA methylation in the dorsal hippocampus. Although these data provide valuable insight into the chromatin modifications that mediate the memory-enhancing effects of E2, epigenetic regulation of gene expression is enormously complex. Therefore, more research is needed to fully understand how E2 and other hormones employ epigenetic alterations to shape behavior. This review discusses the epigenetic alterations shown thus far to regulate hippocampal memory, briefly reviews the effects of E2 on hippocampal function, and describes in detail our work on epigenetic regulation of estrogenic memory enhancement. Copyright © 2014 Elsevier Inc. All rights reserved.

Dose additive effects of simvastatin and dipentyl phthalate on testosterone production in the fetal testis: A cummulative risk perspective

EPA Science Inventory

Sex differentiation of the mammalian reproductive tract is a highly regulated process that is driven, in part, by fetal testosterone (T) production. In utero exposure to phthalate esters (PE) during sex differentiation can cause reproductive tract malformations in rats. PE alter ...

Simvastatin and dipentyl phthalate lower testosterone production and exhibit dose additive effects on the fetal testis via distinct mechanistic pathways

EPA Science Inventory

Sex differentiation of the mammalian reproductive tract is a highly regulated process that is driven, in part, by fetal testosterone (T) production. In utero exposure to phthalate esters (PE) during sex differentiation can result in reproductive tract malformations in rats. PE al...

Fundamentals of Title IV Administration: From Applying to Creating Reports, 2003-2004.

ERIC Educational Resources Information Center

Office of Federal Student Aid (ED), Washington, DC.

This document provides a Fundamentals of Title IV Administration Workshop Agenda. The agenda includes an introduction and high level overview: the process in general; history of the programs; laws and regulations; and overview of the programs. Following this is a section on applying to participate and understand your school's responsibilities…

Assessment Data at Your Fingertips: Advances Allow for Timely Reporting

ERIC Educational Resources Information Center

Bolch, Matt

2009-01-01

The ever-increasing standards of No Child Left Behind regulations and various state assessments have put more pressure on teachers and administrators to monitor the learning process. Fortunately, the advent of technology is allowing teachers to test more often to prepare students for high-stakes tests and for districts to understand results for…

Fingerprints in Place of Passwords: A Study of Technology Adoption in the Nursing Profession

ERIC Educational Resources Information Center

Francisco, James R.

2010-01-01

Health care is one of the most highly regulated industries in the United States. The Health Insurance Portability and Accountability Act of 1996 (HIPAA) mandates the implementation of information systems security to protect the personal information of patients. Properly planned implementations ease the process of introducing new technologies like…

Longitudinal study of self-regulation, positive parenting, and adjustment problems among physically abused children.

PubMed

Kim-Spoon, Jungmeen; Haskett, Mary E; Longo, Gregory S; Nice, Rachel

2012-02-01

Research using normative and high-risk samples indicates a significant link between problems with self-regulation and child maladjustment. Nevertheless, little is known about the processes that may modify the link between self-regulation and maladjustment. This longitudinal study examined the joint contributions of child self-regulation and positive parenting behaviors to the development of externalizing and internalizing symptomatology spanning from preschool to 1st grade. Data were collected on a total of 95 physically abused children (58% boys); our longitudinal analyses involved 43 children at Time 1 (preschool), 63 children at Time 2 (kindergarten), and 54 children at Time 3 (1st grade). Children's self-regulation was measured by parent report, and their externalizing and internalizing symptomatology was evaluated by teachers. Parents completed self-report measures of positive parenting. Our structural equation modeling analyses revealed positive parenting as a protective factor that attenuated the concurrent association between low self-regulation and externalizing symptomatology among physically abused children. Our findings regarding longitudinal changes in children's externalizing symptomatology supported the differential susceptibility hypothesis: Physically abused children who were at greater risk due to low levels of self-regulation were more susceptible to the beneficial effects of positive parenting, compared to those with high levels of self-regulation. Findings suggest that although physical abuse presents formidable challenges that interfere with the development of adaptive self-regulation, positive parenting behaviors may ameliorate the detrimental effects of maladaptive self-regulation on the development of externalizing symptomatology. In addition, the positive and negative effects of caregiving behaviors were more prominent among physically abused children at great risk due to low self-regulation. Findings from the present study highlight the importance of attending to positive parenting behaviors and child self-regulation when working with physically abused children who are exhibiting externalizing symptomatology. Copyright © 2012 Elsevier Ltd. All rights reserved.

Longitudinal study of self-regulation, positive parenting, and adjustment problems among physically abused children

PubMed Central

Kim, Jungmeen; Haskett, Mary E.; Longo, Gregory S.; Nice, Rachel

2012-01-01

Objective Research using normative and high-risk samples indicates a significant link between problems with self-regulation and child maladjustment. Nevertheless, little is known about the processes that may modify the link between self-regulation and maladjustment. This longitudinal study examined the joint contributions of child self-regulation and positive parenting behaviors to the development of externalizing and internalizing symptomatology spanning from preschool to 1st grade. Methods Data were collected on a total of 95 physically abused children (58% boys); our longitudinal analyses involved 43 children at Time 1 (preschool), 63 children at Time 2 (kindergarten), and 54 children at Time 3 (1st grade). Children's self-regulation was measured by parent report, and their externalizing and internalizing symptomatology was evaluated by teachers. Parents completed self-report measures of positive parenting. Results Our structural equation modeling analyses revealed positive parenting as a protective factor that attenuated the concurrent association between low self-regulation and externalizing symptomatology among physically abused children. Our findings regarding longitudinal changes in children's externalizing symptomatology supported the differential susceptibility hypothesis: Physically abused children who were at greater risk due to low levels of self-regulation were more susceptible to the beneficial effects of positive parenting, compared to those with high levels of self-regulation. Conclusions Findings suggest that although physical abuse presents formidable challenges that interfere with the development of adaptive self-regulation, positive parenting behaviors may ameliorate the detrimental effects of maladaptive self-regulation on the development of externalizing symptomatology. In addition, the positive and negative effects of caregiving behaviors were more prominent among physically abused children at great risk due to low self-regulation. Practice Implications Findings from the present study highlight the importance of attending to positive parenting behaviors and child self-regulation when working with physically abused children who are exhibiting externalizing symptomatology. PMID:22398303

Writing Regulation Processes in Higher Education: A Review of Two Decades of Empirical Research

ERIC Educational Resources Information Center

Sala-Bubaré, Anna; Castelló, Montserrat

2018-01-01

In Higher Education (HE), writers need to regulate their writing processes in order to achieve their communicative goals. Although critical for academic success and knowledge construction, writing regulation processes have been mainly researched in compulsory education rather than in HE, with no systematic review focused on this context. The…

Elevated urinary urea by high-protein diet could be one of the inducements of bladder disorders.

PubMed

Liu, Ming; Li, Min; Liu, Jiangfeng; Wang, Hongkai; Zhong, Dandan; Zhou, Hong; Yang, Baoxue

2016-02-16

Previous work found that urea accumulation in urothelial cells caused by urea transporter B knockout led to DNA damage and apoptosis that contributed to the carcinogenesis. The purpose of this study is to explore the potential connection between high urinary urea concentration and the bladder disorders. A high protein diet rat model was conducted by feeding with 40 % protein diet. In-silico modeling and algorithm, based on the results of microarray and proteomics from the bladder urothelium, were used for the reconstruction of accurate cellular networks and the identification of novel master regulators in the high-protein diet rat model. Pathway and biological process enrichment analysis were used to characterize predicted targets of candidate mRNAs/proteins. The expression pattern of the most significant master regulators was evaluated by qPCR and immunohistochemistry. Based on the analysis of different expressed mRNAs/proteins, 15 significant ones (CRP, MCPT2, MCPT9, EPXH2, SERPING1, SRGN, CDKN1C, CDK6, CCNB1, PCNA, BAX, MAGEB16, SERPINE1, HSPA2, FOS) were highly identified and verified by qPCR and immunohistochemistry. They were involved in immune and inflammatory response, cell cycle arrest, apoptosis and pathways in cancer. These abnormally activated processes caused the bladder interstitial congestion and inflammatory infiltrates under the thinner urothelium, cell desquamation, cytoplasm vacuolization, nucleus swelling and malformation in the high-protein diet group. We provided evidences that high urinary urea concentration caused by high-protein diet might be a potential carcinogenic factor in bladder.

Molecular Programs Underlying Asymmetric Stem Cell Division and Their Disruption in Malignancy.

PubMed

Mukherjee, Subhas; Brat, Daniel J

2017-01-01

Asymmetric division of stem cells is a highly conserved and tightly regulated process by which a single stem cell produces two unequal daughter cells. One retains its stem cell identity while the other becomes specialized through a differentiation program and loses stem cell properties. Coordinating these events requires control over numerous intra- and extracellular biological processes and signaling networks. In the initial stages, critical events include the compartmentalization of fate determining proteins within the mother cell and their subsequent passage to the appropriate daughter cell in order to direct their destiny. Disturbance of these events results in an altered dynamic of self-renewing and differentiation within the cell population, which is highly relevant to the growth and progression of cancer. Other critical events include proper asymmetric spindle assembly, extrinsic regulation through micro-environmental cues, and non-canonical signaling networks that impact cell division and fate determination. In this review, we discuss mechanisms that maintain the delicate balance of asymmetric cell division in normal tissues and describe the current understanding how some of these mechanisms are deregulated in cancer.

The TOR Signaling Network in the Model Unicellular Green Alga Chlamydomonas reinhardtii.

PubMed

Pérez-Pérez, María Esther; Couso, Inmaculada; Crespo, José L

2017-07-12

Cell growth is tightly coupled to nutrient availability. The target of rapamycin (TOR) kinase transmits nutritional and environmental cues to the cellular growth machinery. TOR functions in two distinct multiprotein complexes, termed TOR complex 1 (TORC1) and TOR complex 2 (TORC2). While the structure and functions of TORC1 are highly conserved in all eukaryotes, including algae and plants, TORC2 core proteins seem to be missing in photosynthetic organisms. TORC1 controls cell growth by promoting anabolic processes, including protein synthesis and ribosome biogenesis, and inhibiting catabolic processes such as autophagy. Recent studies identified rapamycin-sensitive TORC1 signaling regulating cell growth, autophagy, lipid metabolism, and central metabolic pathways in the model unicellular green alga Chlamydomonas reinhardtii . The central role that microalgae play in global biomass production, together with the high biotechnological potential of these organisms in biofuel production, has drawn attention to the study of proteins that regulate cell growth such as the TOR kinase. In this review we discuss the recent progress on TOR signaling in algae.

The TOR Signaling Network in the Model Unicellular Green Alga Chlamydomonas reinhardtii

PubMed Central

Pérez-Pérez, María Esther; Crespo, José L.

2017-01-01

Cell growth is tightly coupled to nutrient availability. The target of rapamycin (TOR) kinase transmits nutritional and environmental cues to the cellular growth machinery. TOR functions in two distinct multiprotein complexes, termed TOR complex 1 (TORC1) and TOR complex 2 (TORC2). While the structure and functions of TORC1 are highly conserved in all eukaryotes, including algae and plants, TORC2 core proteins seem to be missing in photosynthetic organisms. TORC1 controls cell growth by promoting anabolic processes, including protein synthesis and ribosome biogenesis, and inhibiting catabolic processes such as autophagy. Recent studies identified rapamycin-sensitive TORC1 signaling regulating cell growth, autophagy, lipid metabolism, and central metabolic pathways in the model unicellular green alga Chlamydomonas reinhardtii. The central role that microalgae play in global biomass production, together with the high biotechnological potential of these organisms in biofuel production, has drawn attention to the study of proteins that regulate cell growth such as the TOR kinase. In this review we discuss the recent progress on TOR signaling in algae. PMID:28704927

Chemicals to enhance microalgal growth and accumulation of high-value bioproducts

PubMed Central

Yu, Xinheng; Chen, Lei; Zhang, Weiwen

2015-01-01

Photosynthetic microalgae have attracted significant attention as they can serve as important sources for cosmetic, food and pharmaceutical products, industrial materials and even biofuel biodiesels. However, current productivity of microalga-based processes is still very low, which has restricted their scale-up application. In addition to various efforts in strain improvement and cultivation optimization, it was proposed that the productivity of microalga-based processes can also be increased using various chemicals to trigger or enhance cell growth and accumulation of bioproducts. Herein, we summarized recent progresses in applying chemical triggers or enhancers to improve cell growth and accumulation of bioproducts in algal cultures. Based on their enhancing mechanisms, these chemicals can be classified into four categories:chemicals regulating biosynthetic pathways, chemicals inducing oxidative stress responses, phytohormones and analogs regulating multiple aspects of microalgal metabolism, and chemicals directly as metabolic precursors. Taken together, the early researches demonstrated that the use of chemical stimulants could be a very effective and economical way to improve cell growth and accumulation of high-value bioproducts in large-scale cultivation of microalgae. PMID:25741321

Epigenomics and human adaptation to high altitude.

PubMed

Julian, Colleen G

2017-11-01

Over the past decade, major technological and analytical advancements have propelled efforts toward identifying the molecular mechanisms that govern human adaptation to high altitude. Despite remarkable progress with respect to the identification of adaptive genomic signals that are strongly associated with the "hypoxia-tolerant" physiological characteristics of high-altitude populations, many questions regarding the fundamental biological processes underlying human adaptation remain unanswered. Vital to address these enduring questions will be determining the role of epigenetic processes, or non-sequence-based features of the genome, that are not only critical for the regulation of transcriptional responses to hypoxia but heritable across generations. This review proposes that epigenomic processes are involved in shaping patterns of adaptation to high altitude by influencing adaptive potential and phenotypic variability under conditions of limited oxygen supply. Improved understanding of the interaction between genetic, epigenetic, and environmental factors holds great promise to provide deeper insight into the mechanisms underlying human adaptive potential, and clarify its implications for biomedical research. Copyright © 2017 the American Physiological Society.

Cell volume regulation and apoptotic volume decrease in rat distal colon superficial enterocytes.

PubMed

Antico, Stefania; Lionetto, Maria Giulia; Giordano, Maria Elena; Caricato, Roberto; Schettino, Trifone

2013-01-01

The colon epithelium is physiologically exposed to osmotic stress, and the activation of cell volume regulation mechanisms is essential in colonocyte physiology. Moreover, colon is characterized by a high apoptotic rate of mature cells balancing the high division rate of stem cells. The aim of the present work was to investigate the main cell volume regulation mechanisms in rat colon surface colonocytes and their role in apoptosis. Cell volume changes were measured by light microscopy and video imaging on colon explants; apoptosis sign appearance was monitored by confocal microscopy on annexin V/propidium iodide labeled explants. Superficial colonocytes showed a dynamic regulation of their cell volume during anisosmotic conditions with a Regulatory Volume Increase (RVI) response following hypertonic shrinkage and Regulatory Volume Decrease (RVD) response following hypotonic swelling. RVI was completely inhibited by bumetanide, while RVD was completely abolished by high K(+) or iberiotoxin treatment and by extracellular Ca(2+) removal. DIDS incubation was also able to affect the RVD response. When colon explants were exposed to H2O2 as apoptotic inducer, colonocytes underwent an isotonic volume decrease ascribable to Apoptotic Volume Decrease (AVD) within about four hours of exposure. AVD was shown to precede annexin V positivity. It was also inhibited by high K(+) or iberiotoxin treatment. Interestingly, treatment with iberiotoxin significantly inhibited apoptosis progression. In rat superficial colonocytes K(+) efflux through high conductance Ca(2+)-activated K(+) channels (BK channels) was demonstrated to be the main mechanism of RVD and to plays also a crucial role in the AVD process and in the progression of apoptosis. © 2013 S. Karger AG, Basel.

Butyrate and bioactive proteolytic form of Wnt-5a regulate colonic epithelial proliferation and spatial development

PubMed Central

Uchiyama, Kazuhiko; Sakiyama, Toshio; Hasebe, Takumu; Musch, Mark W.; Miyoshi, Hiroyuki; Nakagawa, Yasushi; He, Tong-Chuan; Lichtenstein, Lev; Naito, Yuji; Itoh, Yoshito; Yoshikawa, Toshikazu; Jabri, Bana; Stappenbeck, Thaddeus; Chang, Eugene B.

2016-01-01

Proliferation and spatial development of colonic epithelial cells are highly regulated along the crypt vertical axis, which, when perturbed, can result in aberrant growth and carcinogenesis. In this study, two key factors were identified that have important and counterbalancing roles regulating these processes: pericrypt myofibroblast-derived Wnt-5a and the microbial metabolite butyrate. Cultured YAMC cell proliferation and heat shock protein induction were analzyed after butryate, conditioned medium with Wnt5a activity, and FrzB containing conditioned medium. In vivo studies to modulate Hsp25 employed intra-colonic wall Hsp25 encoding lentivirus. To silence Wnt-5a in vivo, intra-colonic wall Wnt-5a silencing RNA was used. Wnt-5a, secreted by stromal myofibroblasts of the lower crypt, promotes proliferation through canonical β-catenin activation. Essential to this are two key requirements: (1) proteolytic conversion of the highly insoluble ~40 kD Wnt-5a protein to a soluble 36 mer amino acid peptide that activates epithelial β-catenin and cellular proliferation, and (2) the simultaneous inhibition of butyrate-induced Hsp25 by Wnt-5a which is necessary to arrest the proliferative process in the upper colonic crypt. The interplay and spatial gradients of these factors insures that crypt epithelial cell proliferation and development proceed in an orderly fashion, but with sufficient plasticity to adapt to physiological perturbations including inflammation. PMID:27561676

Gas Flows in Dual Active Galactic Nuclei

NASA Astrophysics Data System (ADS)

Mueller Sanchez, Francisco; Comerford, Julia M.; Davies, Richard; Treister, Ezequiel; Privon, George C.; Nevin, Becky

2018-06-01

Dual Active Galactic Nuclei (AGN) are the Rosetta stone to understand the role of galaxy mergers in triggering nuclear activity and regulating black hole (BH) and galaxy growth. But very little is known about the physical processes required to effectively trigger AGN activity and regulate the growth of the two BHs. The work I will present here characterizes for the first time the properties of the stars, gas (molecular, ionized, and highly-ionized) and dust in all the confirmed dual AGN at z < 0.05, using Keck/OSIRIS, VLT/SINFONI, SOFIA/FORCAST, and HST data. I will focus on the interplay between the several complex processes observed in dual AGN, using as an example the prototypical merger system NGC 6240: vigorous star formation, two AGNs, outflowing winds of ionized gas, rippling dust and gas lanes, and tidal tails. In this galaxy, we observe for the first time a dual outflow of different species of gas: an AGN-driven outflow of highly-ionized gas to the northeast and a starburst-driven outflow of ionized hydrogen to the northwest. This shows that stellar feedback and supermassive black hole feedback can work in tandem to regulate the stellar growth of a galaxy after a merger event. These results open a new door to studies of dual AGN and AGN pairs in general, and enable dual AGN to be used, for the first time, for studies of galaxy evolution.

Differential miRNA expression in B cells is associated with inter-individual differences in humoral immune response to measles vaccination.

PubMed

Haralambieva, Iana H; Kennedy, Richard B; Simon, Whitney L; Goergen, Krista M; Grill, Diane E; Ovsyannikova, Inna G; Poland, Gregory A

2018-01-01

MicroRNAs are important mediators of post-transcriptional regulation of gene expression through RNA degradation and translational repression, and are emerging biomarkers of immune system activation/response after vaccination. We performed Next Generation Sequencing (mRNA-Seq) of intracellular miRNAs in measles virus-stimulated B and CD4+ T cells from high and low antibody responders to measles vaccine. Negative binomial generalized estimating equation (GEE) models were used for miRNA assessment and the DIANA tool was used for gene/target prediction and pathway enrichment analysis. We identified a set of B cell-specific miRNAs (e.g., miR-151a-5p, miR-223, miR-29, miR-15a-5p, miR-199a-3p, miR-103a, and miR-15a/16 cluster) and biological processes/pathways, including regulation of adherens junction proteins, Fc-receptor signaling pathway, phosphatidylinositol-mediated signaling pathway, growth factor signaling pathway/pathways, transcriptional regulation, apoptosis and virus-related processes, significantly associated with neutralizing antibody titers after measles vaccination. No CD4+ T cell-specific miRNA expression differences between high and low antibody responders were found. Our study demonstrates that miRNA expression directly or indirectly influences humoral immunity to measles vaccination and suggests that B cell-specific miRNAs may serve as useful predictive biomarkers of vaccine humoral immune response.

The EMO-Model: An Agent-Based Model of Primate Social Behavior Regulated by Two Emotional Dimensions, Anxiety-FEAR and Satisfaction-LIKE

PubMed Central

Evers, Ellen; de Vries, Han; Spruijt, Berry M.; Sterck, Elisabeth H. M.

2014-01-01

Agent-based models provide a promising tool to investigate the relationship between individuals’ behavior and emerging group-level patterns. An individual’s behavior may be regulated by its emotional state and its interaction history with specific individuals. Emotional bookkeeping is a candidate mechanism to keep track of received benefits from specific individuals without requiring high cognitive abilities. However, how this mechanism may work is difficult to study in real animals, due to the complexity of primate social life. To explore this theoretically, we introduce an agent-based model, dubbed EMO-model, in which we implemented emotional bookkeeping. In this model the social behaviors of primate-like individuals are regulated by emotional processes along two dimensions. An individual’s emotional state is described by an aversive and a pleasant dimension (anxiety and satisfaction) and by its activating quality (arousal). Social behaviors affect the individuals’ emotional state. To implement emotional bookkeeping, the receiver of grooming assigns an accumulated affiliative attitude (LIKE) to the groomer. Fixed partner-specific agonistic attitudes (FEAR) reflect the stable dominance relations between group members. While the emotional state affects an individual’s general probability of executing certain behaviors, LIKE and FEAR affect the individual’s partner-specific behavioral probabilities. In this way, emotional processes regulate both spontaneous behaviors and appropriate responses to received behaviors, while emotional bookkeeping via LIKE attitudes regulates the development and maintenance of affiliative relations. Using an array of empirical data, the model processes were substantiated and the emerging model patterns were partially validated. The EMO-model offers a framework to investigate the emotional bookkeeping hypothesis theoretically and pinpoints gaps that need to be investigated empirically. PMID:24504194

The EMO-model: an agent-based model of primate social behavior regulated by two emotional dimensions, anxiety-FEAR and satisfaction-LIKE.

PubMed

Evers, Ellen; de Vries, Han; Spruijt, Berry M; Sterck, Elisabeth H M

2014-01-01

Agent-based models provide a promising tool to investigate the relationship between individuals' behavior and emerging group-level patterns. An individual's behavior may be regulated by its emotional state and its interaction history with specific individuals. Emotional bookkeeping is a candidate mechanism to keep track of received benefits from specific individuals without requiring high cognitive abilities. However, how this mechanism may work is difficult to study in real animals, due to the complexity of primate social life. To explore this theoretically, we introduce an agent-based model, dubbed EMO-model, in which we implemented emotional bookkeeping. In this model the social behaviors of primate-like individuals are regulated by emotional processes along two dimensions. An individual's emotional state is described by an aversive and a pleasant dimension (anxiety and satisfaction) and by its activating quality (arousal). Social behaviors affect the individuals' emotional state. To implement emotional bookkeeping, the receiver of grooming assigns an accumulated affiliative attitude (LIKE) to the groomer. Fixed partner-specific agonistic attitudes (FEAR) reflect the stable dominance relations between group members. While the emotional state affects an individual's general probability of executing certain behaviors, LIKE and FEAR affect the individual's partner-specific behavioral probabilities. In this way, emotional processes regulate both spontaneous behaviors and appropriate responses to received behaviors, while emotional bookkeeping via LIKE attitudes regulates the development and maintenance of affiliative relations. Using an array of empirical data, the model processes were substantiated and the emerging model patterns were partially validated. The EMO-model offers a framework to investigate the emotional bookkeeping hypothesis theoretically and pinpoints gaps that need to be investigated empirically.

Long non-coding RNAs (LncRNA) regulated by transforming growth factor (TGF) β: LncRNA-hit-mediated TGFβ-induced epithelial to mesenchymal transition in mammary epithelia.

PubMed

Richards, Edward J; Zhang, Gu; Li, Zhu-Peng; Permuth-Wey, Jennifer; Challa, Sridevi; Li, Yajuan; Kong, William; Dan, Su; Bui, Marilyn M; Coppola, Domenico; Mao, Wei-Min; Sellers, Thomas A; Cheng, Jin Q

2015-03-13

Long noncoding RNAs (lncRNAs) are emerging as key regulators in various biological processes. Epithelial-to-mesenchymal transition (EMT) is a developmental process hijacked by tumor cells to depart from the primary tumor site, invade surrounding tissue, and establish distant metastases. Transforming growth factor β (TGFβ) signaling has been shown to be a major inducer of EMT and to facilitate breast cancer metastasis. However, the role of lncRNAs in this process remains largely unknown. Here we report a genome-wide lncRNA profile in mouse mammary epithelial NMuMG cells upon TGFβ induction of EMT. Among 10,802 lncRNAs profiled, over 600 were up-regulated and down-regulated during the EMT, respectively. Furthermore, we identify that lncRNA-HIT (HOXA transcript induced by TGFβ) mediates TGFβ function, i.e. depletion of lncRNA-HIT inhibits TGFβ-induced migration, invasion, and EMT in NMuMG. LncRNA-HIT is also significantly elevated in the highly metastatic 4T1 cells. Knockdown of lncRNA-HIT in 4T1 results in decrease of cell migration, invasion, tumor growth, and metastasis. E-cadherin was identified as a major target of lncRNA-HIT. Moreover, lncRNA-HIT is conserved in humans and elevated expression associates with more invasive human primary breast carcinoma. Collectively, these data suggest that a subset of lncRNAs such as lncRNA-HIT play a significant role in regulation of EMT and breast cancer invasion and metastasis, and could be potential therapeutic targets in breast cancers. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Temporal global expression data reveal known and novel salicylate-impacted processes and regulators mediating powdery mildew growth and reproduction on Arabidopsis.

PubMed

Chandran, Divya; Tai, Yu Chuan; Hather, Gregory; Dewdney, Julia; Denoux, Carine; Burgess, Diane G; Ausubel, Frederick M; Speed, Terence P; Wildermuth, Mary C

2009-03-01

Salicylic acid (SA) is a critical mediator of plant innate immunity. It plays an important role in limiting the growth and reproduction of the virulent powdery mildew (PM) Golovinomyces orontii on Arabidopsis (Arabidopsis thaliana). To investigate this later phase of the PM interaction and the role played by SA, we performed replicated global expression profiling for wild-type and SA biosynthetic mutant isochorismate synthase1 (ics1) Arabidopsis from 0 to 7 d after infection. We found that ICS1-impacted genes constitute 3.8% of profiled genes, with known molecular markers of Arabidopsis defense ranked very highly by the multivariate empirical Bayes statistic (T(2) statistic). Functional analyses of T(2)-selected genes identified statistically significant PM-impacted processes, including photosynthesis, cell wall modification, and alkaloid metabolism, that are ICS1 independent. ICS1-impacted processes include redox, vacuolar transport/secretion, and signaling. Our data also support a role for ICS1 (SA) in iron and calcium homeostasis and identify components of SA cross talk with other phytohormones. Through our analysis, 39 novel PM-impacted transcriptional regulators were identified. Insertion mutants in one of these regulators, PUX2 (for plant ubiquitin regulatory X domain-containing protein 2), results in significantly reduced reproduction of the PM in a cell death-independent manner. Although little is known about PUX2, PUX1 acts as a negative regulator of Arabidopsis CDC48, an essential AAA-ATPase chaperone that mediates diverse cellular activities, including homotypic fusion of endoplasmic reticulum and Golgi membranes, endoplasmic reticulum-associated protein degradation, cell cycle progression, and apoptosis. Future work will elucidate the functional role of the novel regulator PUX2 in PM resistance.

Effect of an Antimicrobial Compound on Different Processes within the Oscillation of Min Proteins in E. coli Bacterial Cells

NASA Astrophysics Data System (ADS)

Giuliani, Maximiliano; Dutcher, John

2013-03-01

A key step in the life of a bacterium is its division into two daughter cells of equal size. This process is carefully controlled and regulated so that equal partitioning of the cellular machinery is obtained. In E. coli, this regulation is accomplished, in part, by the Min protein system. The Min proteins undergo an oscillation between the poles of rod-shaped E. coli bacteria. We use high magnification, time-resolved total internal reflection fluorescence microscopy to characterize the temporal distributions of different processes within the oscillation: the MinD-MinE interaction time, the residence time for membrane bound MinD, and the recruitment time for MinD to be observed at the opposite pole. We also characterize the change in each of these processes in the presence of the antimicrobial compound polymyxin B (PMB). We show that the times corresponding to the removal of MinD from one pole and the recruitment of MinD at the opposite pole are correlated. We explain this correlation through the existence of a concentration threshold. The effect of PMB on the concentration threshold is used to identify which process within the oscillation is most affected.

Functional analysis of a regulator of G-protein signaling CgRGS1 in the rubber tree anthracnose fungus Colletotrichum gloeosporioides.

PubMed

Liu, Zhi-Qiang; Wu, Man-Li; Ke, Zhi-Jian; Liu, Wen-Bo; Li, Xiao-Yu

2018-04-01

Colletotrichum gloeosporioides is the causal agent of rubber anthracnose, which is also one of the important biological factors threatening the development of natural rubber industry in the world. Regulators of G-protein signaling (RGS) are key negative regulators of G-proteins, which play important roles in growth, development and pathogenic processes of plant pathogens. In this study, a RGS gene CgRGS1 was functionally characterized in C. gloeosporioides. Compared to the wild type, the CgRGS1 deletion mutant had slow vegetative growth, reduced conidia with multi-end germination, low appressorium formation rate, high resistance to oxidative stress and SDS. Moreover, the mutant was sensitive to osmotic pressure and showed decreased virulence. In conclusion, CgRGS1 is involved in regulation of vegetative growth, conidiation, germination, appressorium formation, oxidative stress, osmotic pressure response and pathogenicity in C. gloeosporioides.

PDSM, a motif for phosphorylation-dependent SUMO modification

PubMed Central

Hietakangas, Ville; Anckar, Julius; Blomster, Henri A.; Fujimoto, Mitsuaki; Palvimo, Jorma J.; Nakai, Akira; Sistonen, Lea

2006-01-01

SUMO (small ubiquitin-like modifier) modification regulates many cellular processes, including transcription. Although sumoylation often occurs on specific lysines within the consensus tetrapeptide ΨKxE, other modifications, such as phosphorylation, may regulate the sumoylation of a substrate. We have discovered PDSM (phosphorylation-dependent sumoylation motif), composed of a SUMO consensus site and an adjacent proline-directed phosphorylation site (ΨKxExxSP). The highly conserved motif regulates phosphorylation-dependent sumoylation of multiple substrates, such as heat-shock factors (HSFs), GATA-1, and myocyte enhancer factor 2. In fact, the majority of the PDSM-containing proteins are transcriptional regulators. Within the HSF family, PDSM is conserved between two functionally distinct members, HSF1 and HSF4b, whose transactivation capacities are repressed through the phosphorylation-dependent sumoylation. As the first recurrent sumoylation determinant beyond the consensus tetrapeptide, the PDSM provides a valuable tool in predicting new SUMO substrates. PMID:16371476

p53 regulates cytoskeleton remodeling to suppress tumor progression.

PubMed

Araki, Keigo; Ebata, Takahiro; Guo, Alvin Kunyao; Tobiume, Kei; Wolf, Steven John; Kawauchi, Keiko

2015-11-01

Cancer cells possess unique characteristics such as invasiveness, the ability to undergo epithelial-mesenchymal transition, and an inherent stemness. Cell morphology is altered during these processes and this is highly dependent on actin cytoskeleton remodeling. Regulation of the actin cytoskeleton is, therefore, important for determination of cell fate. Mutations within the TP53 (tumor suppressor p53) gene leading to loss or gain of function (GOF) of the protein are often observed in aggressive cancer cells. Here, we highlight the roles of p53 and its GOF mutants in cancer cell invasion from the perspective of the actin cytoskeleton; in particular its reorganization and regulation by cell adhesion molecules such as integrins and cadherins. We emphasize the multiple functions of p53 in the regulation of actin cytoskeleton remodeling in response to the extracellular microenvironment, and oncogene activation. Such an approach provides a new perspective in the consideration of novel targets for anti-cancer therapy.

Lipids in the cell: organisation regulates function.

PubMed

Santos, Ana L; Preta, Giulio

2018-06-01

Lipids are fundamental building blocks of all cells and play important roles in the pathogenesis of different diseases, including inflammation, autoimmune disease, cancer, and neurodegeneration. The lipid composition of different organelles can vary substantially from cell to cell, but increasing evidence demonstrates that lipids become organised specifically in each compartment, and this organisation is essential for regulating cell function. For example, lipid microdomains in the plasma membrane, known as lipid rafts, are platforms for concentrating protein receptors and can influence intra-cellular signalling. Lipid organisation is tightly regulated and can be observed across different model organisms, including bacteria, yeast, Drosophila, and Caenorhabditis elegans, suggesting that lipid organisation is evolutionarily conserved. In this review, we summarise the importance and function of specific lipid domains in main cellular organelles and discuss recent advances that investigate how these specific and highly regulated structures contribute to diverse biological processes.

Self-Regulation and Implicit Attitudes Toward Physical Activity Influence Exercise Behavior.

PubMed

Padin, Avelina C; Emery, Charles F; Vasey, Michael; Kiecolt-Glaser, Janice K

2017-08-01

Dual-process models of health behavior posit that implicit and explicit attitudes independently drive healthy behaviors. Prior evidence indicates that implicit attitudes may be related to weekly physical activity (PA) levels, but the extent to which self-regulation attenuates this link remains unknown. This study examined the associations between implicit attitudes and self-reported PA during leisure time among 150 highly active young adults and evaluated the extent to which effortful control (one aspect of self-regulation) moderated this relationship. Results indicated that implicit attitudes toward exercise were unrelated to average workout length among individuals with higher effortful control. However, those with lower effortful control and more negative implicit attitudes reported shorter average exercise sessions compared with those with more positive attitudes. Implicit and explicit attitudes were unrelated to total weekly PA. A combination of poorer self-regulation and negative implicit attitudes may leave individuals vulnerable to mental and physical health consequences of low PA.

Production against static electricity

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

Shteiner, A.L.; Minaev, G.S.; Shatkov, O.P.

1978-01-01

Coke industry shops process electrifiable, highly inflammable and explosive substances (benzene, toluene, xylenes, sulfur, coal dust, and coke-oven gas). The electrification of those materials creates a danger of buildup of static electricity charges in them and on the surface of objects interacting with them, followed by an electrical discharge which may cause explosion, fire, or disruption of the technological process. Some of the regulations for protection against static electricity do not reflect modern methods of static electricity control. The regulations are not always observed by workers in the plant services. The main means of protection used to remove static electricitymore » charges in grounding. In many cases it completely drains the charge from the surface of the electrifiable bodies. However, in the processing of compounds with a high specific volumetric electrical resistence grounding is insufficient, since it does not drain the charge from the interior of the substance. Gigh adsorption capacity) are generally met by brown coal low-temperature ompared with predictions using the hourly computer program. The concept of a lumped thermal network for predicting heat losses from in-ground heat storage tanks, developed earlier in the project, has beethe cased-hole log data from various companies and additional comparison factors were calculated for the cased-hole log data. These comparison factors allow for some quantification of these uncalibrated log data.« less

Hypertrophic scar contracture is mediated by the TRPC3 mechanical force transducer via NFkB activation

PubMed Central

Ishise, Hisako; Larson, Barrett; Hirata, Yutaka; Fujiwara, Toshihiro; Nishimoto, Soh; Kubo, Tateki; Matsuda, Ken; Kanazawa, Shigeyuki; Sotsuka, Yohei; Fujita, Kazutoshi; Kakibuchi, Masao; Kawai, Kenichiro

2015-01-01

Wound healing process is a complex and highly orchestrated process that ultimately results in the formation of scar tissue. Hypertrophic scar contracture is considered to be a pathologic and exaggerated wound healing response that is known to be triggered by repetitive mechanical forces. We now show that Transient Receptor Potential (TRP) C3 regulates the expression of fibronectin, a key regulatory molecule involved in the wound healing process, in response to mechanical strain via the NFkB pathway. TRPC3 is highly expressed in human hypertrophic scar tissue and mechanical stimuli are known to upregulate TRPC3 expression in human skin fibroblasts in vitro. TRPC3 overexpressing fibroblasts subjected to repetitive stretching forces showed robust expression levels of fibronectin. Furthermore, mechanical stretching of TRPC3 overexpressing fibroblasts induced the activation of nuclear factor-kappa B (NFκB), a regulator fibronectin expression, which was able to be attenuated by pharmacologic blockade of either TRPC3 or NFκB. Finally, transplantation of TRPC3 overexpressing fibroblasts into mice promoted wound contraction and increased fibronectin levels in vivo. These observations demonstrate that mechanical stretching drives fibronectin expression via the TRPC3-NFkB axis, leading to intractable wound contracture. This model explains how mechanical strain on cutaneous wounds might contribute to pathologic scarring. PMID:26108359

Systematic discovery and characterization of fly microRNAs using 12 Drosophila genomes

PubMed Central

Stark, Alexander; Kheradpour, Pouya; Parts, Leopold; Brennecke, Julius; Hodges, Emily; Hannon, Gregory J.; Kellis, Manolis

2007-01-01

MicroRNAs (miRNAs) are short regulatory RNAs that inhibit target genes by complementary binding in 3′ untranslated regions (3′ UTRs). They are one of the most abundant classes of regulators, targeting a large fraction of all genes, making their comprehensive study a requirement for understanding regulation and development. Here we use 12 Drosophila genomes to define structural and evolutionary signatures of miRNA hairpins, which we use for their de novo discovery. We predict >41 novel miRNA genes, which encompass many unique families, and 28 of which are validated experimentally. We also define signals for the precise start position of mature miRNAs, which suggest corrections of previously known miRNAs, often leading to drastic changes in their predicted target spectrum. We show that miRNA discovery power scales with the number and divergence of species compared, suggesting that such approaches can be successful in human as dozens of mammalian genomes become available. Interestingly, for some miRNAs sense and anti-sense hairpins score highly and mature miRNAs from both strands can indeed be found in vivo. Similarly, miRNAs with weak 5′ end predictions show increased in vivo processing of multiple alternate 5′ ends and have fewer predicted targets. Lastly, we show that several miRNA star sequences score highly and are likely functional. For mir-10 in particular, both arms show abundant processing, and both show highly conserved target sites in Hox genes, suggesting a possible cooperation of the two arms, and their role as a master Hox regulator. PMID:17989255

Caulobacter crescentus Cell Cycle-Regulated DNA Methyltransferase Uses a Novel Mechanism for Substrate Recognition.

PubMed

Woodcock, Clayton B; Yakubov, Aziz B; Reich, Norbert O

2017-08-01

Caulobacter crescentus relies on DNA methylation by the cell cycle-regulated methyltransferase (CcrM) in addition to key transcription factors to control the cell cycle and direct cellular differentiation. CcrM is shown here to efficiently methylate its cognate recognition site 5'-GANTC-3' in single-stranded and hemimethylated double-stranded DNA. We report the K m , k cat , k methylation , and K d for single-stranded and hemimethylated substrates, revealing discrimination of 10 7 -fold for noncognate sequences. The enzyme also shows a similar discrimination against single-stranded RNA. Two independent assays clearly show that CcrM is highly processive with single-stranded and hemimethylated DNA. Collectively, the data provide evidence that CcrM and other DNA-modifying enzymes may use a new mechanism to recognize DNA in a key epigenetic process.

What Are the bona fide GSK3 Substrates?

PubMed

Sutherland, Calum

2011-01-01

Nearly 100 proteins are proposed to be substrates for GSK3, suggesting that this enzyme is a fundamental regulator of almost every process in the cell, in every tissue in the body. However, it is not certain how many of these proposed substrates are regulated by GSK3 in vivo. Clearly, the identification of the physiological functions of GSK3 will be greatly aided by the identification of its bona fide substrates, and the development of GSK3 as a therapeutic target will be highly influenced by this range of actions, hence the need to accurately establish true GSK3 substrates in cells. In this paper the evidence that proposed GSK3 substrates are likely to be physiological targets is assessed, highlighting the key cellular processes that could be modulated by GSK3 activity and inhibition.

Single-Cell and Single-Molecule Analysis of Gene Expression Regulation.

PubMed

Vera, Maria; Biswas, Jeetayu; Senecal, Adrien; Singer, Robert H; Park, Hye Yoon

2016-11-23

Recent advancements in single-cell and single-molecule imaging technologies have resolved biological processes in time and space that are fundamental to understanding the regulation of gene expression. Observations of single-molecule events in their cellular context have revealed highly dynamic aspects of transcriptional and post-transcriptional control in eukaryotic cells. This approach can relate transcription with mRNA abundance and lifetimes. Another key aspect of single-cell analysis is the cell-to-cell variability among populations of cells. Definition of heterogeneity has revealed stochastic processes, determined characteristics of under-represented cell types or transitional states, and integrated cellular behaviors in the context of multicellular organisms. In this review, we discuss novel aspects of gene expression of eukaryotic cells and multicellular organisms revealed by the latest advances in single-cell and single-molecule imaging technology.

Effects of procurement practices on quality of medical device or service received: a qualitative study comparing countries.

PubMed

Lingg, Myriam; Wyss, Kaspar; Durán-Arenas, Luis

2016-08-08

We know little about how procurement of a high-risk medical device (HRMD) affects clinical practice and outcomes. In health systems in high-income countries, and specifically those that maintain a national arthroplasty registry, procurement decisions are frequently guided by long-term clinical results, with the goal of ensuring at least standard quality of HRMDs. But in countries like Mexico, decision-making is often dominated by lowest acquisition price. We set out to study the impact of procurement for orthopaedic HRMDs on clinical procedures and outcomes. We based our qualitative study on 59 in-depth interviews with stakeholders from Mexico, Switzerland, Germany, and UK: orthopaedic specialists, government officials, other experts, and social security system managers or administrators. We took a healthcare delivery approach to capturing and comparing factors that affected the regulations of HRMDs and procurement processes, and to understanding connections between procurement and clinical practice. Our findings demonstrate for procurement processes that the three European countries compared to Mexico don't have similar concerns with regards to their procurement processes. Deficiencies of procurement regulations and practices identified from representatives in Mexico were almost absent in European countries. We identified three areas of deficiency: 1) HRMD regulations based on insufficiently robust clinical evidence (mainly noted by European countries); 2) Follow-up on Health Technology Assessments is inadequate (noted by Mexico) and methodology not always good enough (noted by European countries); and, 3) Lowest-acquisition price often guides procurement decisions and thus may not align with needs of clinical procedures (noted by Mexico and some European countries). Procurement processes for orthopaedic HRMDs may have an impact on clinical procedures and outcomes. A favourable approach is one where orthopaedic specialists are parties to the procurement process, and post-market surveillance data informs decision-making. Actors in the procurement process can improve their impact on clinical procedures and outcomes by developing specific strategies that better align the needs of both, procurement and clinical procedures.

Self-tuning regulator for an interacting CSTR process

NASA Astrophysics Data System (ADS)

Rajendra Mungale, Niraj; Upadhyay, Akshay; Jaganatha Pandian, B.

2017-11-01

In the paper we have laid emphasis on STR that is Self Tuning Regulator and its application for an interacting process. CSTR has a great importance in Chemical Process when we deal with controlling different parameters of a process using CSTR. Basically CSTR is used to maintain a constant liquid temperature in the process. The proposed method called self-tuning regulator, is a different scheme where process parameters are updated and the controller parameters are obtained from the solution of a design problem. The paper deals with STR and methods associated with it.

Quantitative Dynamics of Proteome, Acetylome, and Succinylome during Stem-Cell Differentiation into Hepatocyte-like Cells.

PubMed

Liu, Zekun; Zhang, Qing-Bin; Bu, Chen; Wang, Dawei; Yu, Kai; Gan, Zhixue; Chang, Jianfeng; Cheng, Zhongyi; Liu, Zexian

2018-06-21

Stem-cell differentiation is a complex biological process controlled by a series of functional protein clusters and signaling transductions, especially metabolism-related pathways. Although previous studies have quantified the proteome and phosphoproteome for stem-cell differentiation, the investigation of acylation-mediated regulation is still absent. In this study, we quantitatively profiled the proteome, acetylome, and succinylome in pluripotent human embryonic stem cells (hESCs) and differentiated hepatocyte-like cells (HLCs). In total, 3843 proteins, 185 acetylation sites in 103 proteins, and 602 succinylation sites in 391 proteins were quantified. The quantitative proteome showed that in differentiated HLCs the TGF-β, JAK-STAT, and RAS signaling pathways were activated, whereas ECM-related processes such as sulfates and leucine degradation were depressed. Interestingly, it was observed that the acetylation and succinylation were more intensive in hESCs, whereas protein processing in endoplasmic reticulum and the carbon metabolic pathways were especially highly succinylated. Because the metabolism patterns in pluripotent hESCs and the differentiated HLCs were different, we proposed that the dynamic acylations, especially succinylation, might regulate the Warburg-like effect and TCA cycle during differentiation. Taken together, we systematically profiled the protein and acylation levels of regulation in pluripotent hESCs and differentiated HLCs, and the results indicated the important roles of acylation in pluripotency maintenance and differentiation.

Ecdysone receptor agonism leading to lethal molting ...

EPA Pesticide Factsheets

Molting is a key biological process in growth, development, reproduction and survival in arthropods. Complex neuroendocrine pathways are involved in the regulation of molting and may potentially become targets of environmental endocrine disrupting compounds (EDCs). For example, several classes of pesticides used in agriculture and aquaculture specifically target key endocrine regulators of the molting process. These chemicals may also pose hazards to non-target species by causing molting defects, thus affecting the health of the ecosystems. The present review summarized the available knowledge on molting-related endocrine regulation and disruption in arthropods (with special focus on insects and crustaceans), in order to identify research gaps and develop a toxicity mechanism-based model for environmental hazard and risk assessment. Based on the review, multiple targets in the molting processes that EDCs can interact with were characterized to inform future studies. An adverse outcome pathway (AOP) describing ecdysone receptor agonism leading to incomplete ecdysis associated mortality was developed according to the OECD guideline and evaluated for weight of evidence using the Evolved Bradford Hill Criteria. This review proposed the first invertebrate endocrine disruption AOP and may serve as a knowledge foundation for future environmental studies and AOP development. Development of high throughput toxicology (HTT) programs (e.g., ToxCast, Tox21) and potential a

Mitochondrial respiratory chain complexes as sources and targets of thiol-based redox-regulation.

PubMed

Dröse, Stefan; Brandt, Ulrich; Wittig, Ilka

2014-08-01

The respiratory chain of the inner mitochondrial membrane is a unique assembly of protein complexes that transfers the electrons of reducing equivalents extracted from foodstuff to molecular oxygen to generate a proton-motive force as the primary energy source for cellular ATP-synthesis. Recent evidence indicates that redox reactions are also involved in regulating mitochondrial function via redox-modification of specific cysteine-thiol groups in subunits of respiratory chain complexes. Vice versa the generation of reactive oxygen species (ROS) by respiratory chain complexes may have an impact on the mitochondrial redox balance through reversible and irreversible thiol-modification of specific target proteins involved in redox signaling, but also pathophysiological processes. Recent evidence indicates that thiol-based redox regulation of the respiratory chain activity and especially S-nitrosylation of complex I could be a strategy to prevent elevated ROS production, oxidative damage and tissue necrosis during ischemia-reperfusion injury. This review focuses on the thiol-based redox processes involving the respiratory chain as a source as well as a target, including a general overview on mitochondria as highly compartmentalized redox organelles and on methods to investigate the redox state of mitochondrial proteins. This article is part of a Special Issue entitled: Thiol-Based Redox Processes. Copyright © 2014 Elsevier B.V. All rights reserved.

Perspectives on genetically modified crops and food detection.

PubMed

Lin, Chih-Hui; Pan, Tzu-Ming

2016-01-01

Genetically modified (GM) crops are a major product of the global food industry. From 1996 to 2014, 357 GM crops were approved and the global value of the GM crop market reached 35% of the global commercial seed market in 2014. However, the rapid growth of the GM crop-based industry has also created controversies in many regions, including the European Union, Egypt, and Taiwan. The effective detection and regulation of GM crops/foods are necessary to reduce the impact of these controversies. In this review, the status of GM crops and the technology for their detection are discussed. As the primary gap in GM crop regulation exists in the application of detection technology to field regulation, efforts should be made to develop an integrated, standardized, and high-throughput GM crop detection system. We propose the development of an integrated GM crop detection system, to be used in combination with a standardized international database, a decision support system, high-throughput DNA analysis, and automated sample processing. By integrating these technologies, we hope that the proposed GM crop detection system will provide a method to facilitate comprehensive GM crop regulation. Copyright © 2015. Published by Elsevier B.V.

Impact of the ion transportome of chloroplasts on the optimization of photosynthesis.

PubMed

Szabò, Ildikò; Spetea, Cornelia

2017-06-01

Ions play fundamental roles in all living cells, and their gradients are often essential to fuel transport, regulate enzyme activities, and transduce energy within cells. Regulation of their homeostasis is essential for cell metabolism. Recent results indicate that modulation of ion fluxes might also represent a useful strategy to regulate one of the most important physiological processes taking place in chloroplasts, photosynthesis. Photosynthesis is highly regulated, due to its unique role as a cellular engine for growth in the light. Controlling the balance between ATP and NADPH synthesis is a critical task, and availability of these molecules can limit the overall photosynthetic yield. Photosynthetic organisms optimize photosynthesis in low light, where excitation energy limits CO2 fixation, and minimize photo-oxidative damage in high light by dissipating excess photons. Despite extensive studies of these phenomena, the mechanism governing light utilization in plants is still poorly understood. In this review, we provide an update of the recently identified chloroplast-located ion channels and transporters whose function impacts photosynthetic efficiency in plants. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Monitoring boreal ecosystem phenology with integrated active/passive microwave remote sensing

NASA Technical Reports Server (NTRS)

McDonald, K. C.; Njoku, E.; Kimball, J.; Running, S.; Thompson, C.; Lee, J. K.

2002-01-01

The important role of the high latitudes in the functioning of global processes is becoming well established. The size and remoteness of arctic and boreal ecosystems, however, pose a challenge to quantification of both terrestrial ecosystem processes and their feedbacks to regional and global climate conditions. Boreal and arctic regions form a complex land cover mosaic where vegetation structure, condition and distribution are strongly regulated by environmental factors such as moisture availability, permafrost, growing season length, disturbance and soil nutrients.

Information processing in the primate visual system - An integrated systems perspective

NASA Technical Reports Server (NTRS)

Van Essen, David C.; Anderson, Charles H.; Felleman, Daniel J.

1992-01-01

The primate visual system contains dozens of distinct areas in the cerebral cortex and several major subcortical structures. These subdivisions are extensively interconnected in a distributed hierarchical network that contains several intertwined processing streams. A number of strategies are used for efficient information processing within this hierarchy. These include linear and nonlinear filtering, passage through information bottlenecks, and coordinated use of multiple types of information. In addition, dynamic regulation of information flow within and between visual areas may provide the computational flexibility needed for the visual system to perform a broad spectrum of tasks accurately and at high resolution.

Emotion control in collaborative learning situations: do students regulate emotions evoked by social challenges?

PubMed

Järvenoja, Hanna; Järvelä, Sanna

2009-09-01

During recent decades, self-regulated learning (SRL) has become a major research field. SRL successfully integrates the cognitive and motivational components of learning. Self-regulation is usually seen as an individual process, with the social aspects of regulation conceptualized as one aspect of the context. However, recent research has begun to investigate whether self-regulation processes are complemented by socially shared regulation processes. The presented study investigated what kind of socio-emotional challenges students experience during collaborative learning and whether the students regulate the emotions evoked during these situations. The interplay of the emotion regulation processes between the individual and the group was also studied. The sample for this study was 63 teacher education students who studied in groups of three to five during three collaborative learning tasks. Students' interpretations of experienced social challenges and their attempts to regulate emotions evoked by these challenges were collected following each task using the Adaptive Instrument for the Regulation of Emotions. The results indicated that students experienced a variety of social challenges. Students also reported the use of shared regulation in addition to self-regulation. Finally, the results suggested that intrinsic group dynamics are derived from both individual and social elements of collaborative situations. The findings of the study support the assumption that students can regulate emotions collaboratively as well as individually. The study contributes to our understanding of the social aspects of emotional regulation in collaborative learning contexts.

Tribological evaluation of high-speed steels with a regulated carbide phase

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

Richter, Janusz

2003-06-15

Wear resistance of a commercial steel and titanium-niobium high-speed steels with a regulated carbide phase was evaluated by employing a micro-scale abrasive wear test with alumina particles. The worn volumes and corresponding wear coefficients were the lowest for the new non-ledeburitic grades containing titanium, then the two niobium grades, the conventional (both wrought and by powder metallurgy) steels exhibited the worse wear resistance. Fractography SEM observations together with energy-dispersive X-ray (EDX) chemical analysis revealed the decisive role of the steels' MC particles in the wear process. These carbides influenced the abrasion by stoppage of the wear scars and/or changing theirmore » trajectories. Directional and nondirectional abrasion modes in the steels tested using alumina and carborundum abrasives were found and are discussed.« less

Concise review: Pax6 transcription factor contributes to both embryonic and adult neurogenesis as a multifunctional regulator.

PubMed

Osumi, Noriko; Shinohara, Hiroshi; Numayama-Tsuruta, Keiko; Maekawa, Motoko

2008-07-01

Pax6 is a highly conserved transcription factor among vertebrates and is important in various developmental processes in the central nervous system (CNS), including patterning of the neural tube, migration of neurons, and formation of neural circuits. In this review, we focus on the role of Pax6 in embryonic and postnatal neurogenesis, namely, production of new neurons from neural stem/progenitor cells, because Pax6 is intensely expressed in these cells from the initial stage of CNS development and in neurogenic niches (the subgranular zone of the hippocampal dentate gyrus and the subventricular zone of the lateral ventricle) throughout life. Pax6 is a multifunctional player regulating proliferation and differentiation through the control of expression of different downstream molecules in a highly context-dependent manner.