断层封闭性及其与油气成藏的关系研究-以沾化凹陷孤岛地区为例

Godao area, located in the east of the Zhanhua depression of Jirang sag in Bohai Bay Basin, is the studying area in my dissertation. It is first time that fault sealing properties and the related relationship with the pool forming are studied in Gudao area. On the base of the analysis of the regional tectonics, the author has studied the tertiary structural evolution of the Gudao area and distinguished the fault's level and put forward the distinguishing principle. The geometrical feature, mechanical characters, developmental mechanism and history of the boundary faults in the tectonic unit of this area are all studied and emphasized especially. The buried history of oil-generating depression (that is Gudao depression) and the history of oil and gas migration simultaneously are discussed, the juxtaposition relationship between boundary fault evolutionary history and oil and gas migrated history are expatiated. To the geological condition of the Gudao area, three level faults sealing properties of this area were discussed in detail. Their characteristics of behavior and the intrinsic relationship between their sealing and oil and gas migrated reservoir are elucidated. The pool-forming models related to fault seal are exposed. The author has studied the lithologies of different order of faults, the relationship of occurrence assemblage analysis, normal stress of fault plane in different depth and shale smear factor faults. Then analysis their role in the various faults sealing and confirms fault sealing marks of three different orders faults and exposes the mechanism of fault sealing. Shale smear zone formed by first order fault in lasting activities is one different type of fault breccia and mainly controlled factor to its entrapment of petroleum. Effective sealing threshold value and fault displacement is ascertained. Mainly controlled factor of second fault sealing is bigger compressive stress loaded on fault plane. According to this, quantitatively evaluated index is given. Shale smear zone is necessary condition for second fault stress entrapment. The juxtaposed relationship between the different lithologies within third order faults is most important controlled factor for its sealing. Based on various order of fault sealing features and mechanism in Gudao area, the author proposed three orders of fault sealing models. Shale smear zone sealing model, normal stress sealing model and lithologies juxtaposed sealing model are suggested to first, second and third order fault respectively. The conclusion of this studying has not only the very important theoretical significance and practical value in Gudo area but also the very important guiding role for other areas of related aspects.

东营凹陷岩性油气藏成藏动力学机制和预测

This paper is belonging to Chinese Petrochemical Industry Corporation's key project. Although it is very difficult, it has important theoretical and practical value. Its targets is to make lithological petroleum pool exploration great breakthrough in Dongying sag, by applying advanced theories, the last-minute methods and technology in highly explored zones. By using synthetically multi- discipline theories, methods and technology such as petroleum geology, sedimentology, structure geology, rock mechanics, dynamics of petroleum pool formation, geochemistry, geophysics and so on, and by making full use of computer , the process of petroleum pool forming and distribution rules of lithological petroleum pools have been thoroughly investigated and analyzed in sharp-slope, gentle-slope as well as low-lying region of Dongying sag including dynamic and static. With the study of tectonic stress field, fluid potential field and pressure field, we revealed dynamics condition, distribution rule, control factors and petroleum forming mechanism of lithological pool, and established the forming mode of lithological pool of Dongying sag. The main conclusion as follow: Strata framework, structure framework and sedimentary system of Dongying sag have been established which were the basis of petroleum prediction. There are three kinds of oil source which were from Es4,Es3 and mixed type, also three petroleum forming phases which were the telophase of Dongying stage, Guantao stage and Minghuazhen group, which occur in different geological environment. By using of most advanced numerical modeling software, the space distribution and time evolve of stress field and fluid potential field have been revealed from Esl up to the present. The region with low earth stress and low fluid potential were enrichment region of lithological petroleum pool and fault-block pool. The dynamics mechanism of Lithological petroleum pool in Dongying sag was collocating seal box, abnormity pressure, index number of petroleum forming and static factors on time and space, which was the most important factor of controlling petroleum pool forming, distribution and enrichment. The multi phase active and evolve of seal and unseal about different order fault were main factors of controlling petroleum pool forming of Dongying sag, which have important value for predicting lithological petroleum pool. It is revealed the lithological petroleum pool forming mode that included respective character, forming mechanism and distribution rule in four structural belt, which was a base for lithological petroleum pool prediction. The theories, technology and methods of studying, description, characterize and prediction lithological petroleum pool were established, which have important popularization value. Several lithological pool have been predicted in stress transform, zone, abrupt slope zone, fractured surface changed zone, tosional stress growth zone and abnormity pressure zone with noticeable economic benefit after exploration.

金融工作者的抑郁症状的影响因素及其形成机制研究

Ill-health prevails in the workplace. A key problem encountered in the area of stress management is a lack of research into the way job burnout turns into mental problems, especially depressive symptoms, the most prevalent and costly psychiatric condition in the workplace. This research belongs to a cross-discipline area of industrial psychiatry and organizational behavior, which has seldom been investigated before. This research will contribute to the theoretical development of organizational behavior, especially to stress management and industrial psychiatry. This study aims to explore etiological factors and mechanisms of depressive symptoms of workers in the financial industry. By using literature review, semi-structured interviews and surveys as the major research methods, this Ph.D. study systematically investigated the risk factors of workers’ depressive symptoms within and outside of the work area. These risk factors are worker-work environment fits, work family conflicts, and workers’ psychological vulnerabilities to depression. A thorough literature review and 20 semi-structured interviews of brokers in different kinds of financial markets show the feasibility and necessity of this Ph.D. study when it comes to the issue of financial workers’ depressive symptoms. Two surveys of workplace-etiological factors of depressive symptoms were conducted among 244 financial workers and 1024 financial workers. This cross-sample verification showed that worker-work environment fit was a good framework to study risk factors of workers’ depressive symptoms. Results revealed that job demands-abilities misfit could lead to job burnout which in turn contributed to worker’s depressive symptoms; besides this, work effort-reward imbalance could directly cause workers’ depressive symptoms. Emotional labor enhanced the positive effect of job burnout on workers’ depressive symptoms. In the third study, a prominent risk factor outside of the work area, namely work family conflict, and workers’ psychological vulnerabilities of depression were included with workplace etiological factors to investigate the overall predictive model of depressive symptoms of financial workers. The survey was conducted among the same 1024 financial workers. Results indicated that work effort-reward imbalance, job burnout and work interfering in family life were three external etiological factors of workers’ depressive symptoms. Neuroticism, autonomy and low emotional intelligence were three individual etiological factors which had a positive effect on workers’ depressive symptoms. Moreover, neuroticism enhanced the relationship between job burnout and depressive symptoms as well as between work interfering in family life and depressive symptoms. Autonomy aggravated the relationship between job burnout and depressive symptoms. However, emotional intelligence attenuated the relationship between job burnout and depressive symptoms as well as between work effort-reward imbalance and depressive symptoms. Besides, workers’ dysfunctional attitudes played a partial mediating role in the relationships between above etiological factors and depressive symptoms. In the same sample, research evidence of impairments of workers’ depressive symptoms to their work-life quality was also obtained. Specifically, depressive symptoms could predict workers’ presenteeism, absenteeism and turnover intention. Their subjective well-being was also lowered when suffering more severe depressive symptoms. This research provides a theoretical basis to management practices targeted to set up the Employee Assistance Program or even more specilised rehabilitation programs for workers with depressive symptoms so as to improve their work-life quality and and establish a harmonious enterprise.

中学生抑郁和素质、压力、环境因素的关系及其整合模型研究

As a kind of mood, depression is one of the emotions which people experienced usually. Depressive disorder is one of the common mental diseases. There are about 100 million people in the world be disturbed by depression every year. So it is long history that depression is investigated widely in medicine, psychology, and sociology. There are many theorial problems remain to be solved. Viewed from latest vocuments, the development of depression theory is tending to become more complicated. Most of the prior depression theory focused on relation between one factor and depression. Because depressed individuls have various characteristics and factors that cause depression are different, and each factor can explain only part of depression variance, these prior depression theories are defected. As the knowledge about depression accumulated, the view that depression be caused by multifactor is clearer. There is tendency to integrate these cooperational factor into a model while developing a depression theory. In the present study, depression status of 1625 middle school students from junior 1 to senior 3 are measured using Depression Scale of Middle-school Student which is developed by ourselves. From approach of depressive mood, the present study explored depressive diathesis including attributional style, personality, coping style, and self. The relation among depressive diathesis, stress and depression is analysed. The relation between depression and school life adaptation, depression and cohesion, adaptation in family are also analysed from environmental view. At last, relation among environment, stress, depressive diathesis is examined by using covariance structure modelling. Synthesizing the results from the present study, the following conclusions were drawn: (1) There is grade-characteristics in development of depression in middle school students. Depression degree increased with grade. The main reason may be that the stress middle-school students experience increase and self-acceptance decrease with grade; (2) High depressive diathesis is different from low depressive diathesis. the features of high depressive diathesis are that attributing failure to ability or background, low capacity for status, low sociability, low independence, low self-blame, more illusion. The features of low depressive diathesis are that not attributing failure to ability or background, high capacity for status, high sociability, high independence, high self-acceptance, while facing difficulties, using problem-resolving coping strategy, less self-blame, less illusion. Individuals who have high depressive diathesis showed serious depression, and individuals who have low depressive diathesis showed light depression; (3) Depressive diathesis had accumulative effect on depression. More low depressive diathesis, more light is depression. More high depressive diathesis, more serious is depression; (4) Depressive diathesis can predict present depression and future depression. Predicting present depression is more effective than predicting future depression; (5) Individual who has different depressive diathesis experiences different level of stress. Higher the depressive diathesis individual has, higher stress he will experience. Lower the depressive diathesis individual has, lower stress will he experience; (6) There is correlation between life event pressure and depression. Life event pressure can predict a part of variance of depression. Life event pressure has accumulative effect on depression. More life event and higher life event pressure, more serious depression individual will experience; (7) There exits high correlation between depression and school life adaptation which can predict depression; (8) There is high correlative relation between depression and cohesion, adaptation in family which can predict depression; and (9) Environment have more effect on diathesis than on stress. Diathesis has more effect on depression than stress does. The past depression can predict future depression. This study had enlarged the domain of depressive diathesis such as attributional style, personality, coping style, and self, which are analysed wholly. This study had also enriched the connotation of diathesis=stress theory. Above two aspects are theoretical significance of the study. This study provide a framework of mental health educational curriculum in high school and provide the guideline for prevention and cure of depression. It is the practical significance of this study.

大学生应激应付研究

In this study, we made research on coping with stress in undergraduate students. The whole work included two parts: (a) We developed the Coping Strategies Questionnaire and had it tested. Five kinds of coping strategies were found by factor analysis: Problem Solving, Passive Acceptance, Support Seeking, Emotion Regulation, and Unadaptation. The reliability and validity coefficients of the questionnaire was high. (b) We examined the relations among personality characteristics (Locus of control, Extraversion, Neuroticism), emotion state, cognitive appraisal (psychological pressure, controllability, resource of social support), and the specific coping processes in several specific stressful events. The results indicated that coping have some degree of consistency across different situations which suggested that there is a general coping tendency, and that this general coping tendency, in addition to the above considered variables, have different degree of effects on subjects' choice of specific coping strategies. Finally, theoretical model of the relationship was tested through path analysis.

Contributo para o desenvolvimento de um Instrumento de Investigação Neuropsicológica

Tese apresentada à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Doutor em Ciências Sociais, especialidade em Psicologia

Osmotic stress tolerance mechanisms in Lactococcus lactis

The response of Lactococcus lactis subsp. cremoris NCDO 712 to low water activity (aw) was investigated, both in relation to growth following moderate reductions in the aw and in terms of survival following substantial reduction of the aw with NaCI. Lc.lactis NCDO 712 was capable of growth in the presence of ≤ 4% w/v NaCI and concentrations in excess of 4% w/v were lethal to the cells. The presence of magnesium ions significantly increased the resistance of NCDO 712 to challenge with NaCI and also to challenge with high temperature or low pH. Survival of Lc.lactis NCDO 712 exposed to high NaCI concentrations was growth phase dependent and cells were most sensitive in the early exponential phase of growth. Pre-exposure to 3% w/v NaCI induced limited protection against subsequent challenge with higher NaCI concentrations. The induction was inhibited by chloramphenicol and even when induced, the response did not protect against NaCI concentrations> 10% w/v. When growing at low aw, potassium was accumulated by Lc. lactis NCDO 712 growing at low aw, if the aw was reduced by glucose or fructose, but not by NaCI. Reducing the potassium concentration of chemically defined medium from 20 to 0.5 mM) produced a substantial reduction in the growth rate, if the aw was reduced with NaCI, but not with glucose or fructose. The reduction of the growth rate correlated strongly with a reduction in the cytoplasmic potassium concentration and in cell volume. Addition of the compatible solute glycine betaine, partially reversed the inhibition of growth rate and partially restored the cell volume. The potassium transport system was characterised in cells grown in medium at both high and low aw. It appeared that a single system was present, which was induced approximately two-fold by growth at low aw. Potassium transport was assayed in vitro using cells depleted of potassium; the assay was competitively inhibited by Na+ and by the other monovalent cations NH4+, Li+, and Cs+. There was a strong correlation between the ability of strains of Lc. lactis subsp. lactis and subsp. cremoris to grow at low aw and their ability to accumulate the compatible solute glycine betaine. The Lc. lactis subsp. cremoris strains incapable of growth at NaCI concentrations> 2% w/v did not accumulate glycine betaine when growing at low aw, whereas strains capable of growth at NaCI concentrations up to 4% w/v did. A mutant, extremely sensitive to low aw was isolated from the parent strain Lc. lactis subsp. cremoris MG 1363, a plasmid free derivative of NCDO 712. The parent strain tolerated up to 4% w/v NaCI and actively accumulated glycine betaine when challenged at low aw. The mutant had lost the ability to accumulate glycine betaine and was incapable of growth at NaCI concentrations >2% w/v or the equivalent concentration of glucose. As no other compatible solute seemed capable of substitution for glycine betaine, the data suggest that the traditional; phenotypic speciation of strains on the basis of tolerance to 4% w/v NaCI can be explained as possession or lack of a glycine betaine transport system.

An investigation into mechanisms of visceral pain in rodents

Visceral pain is a debilitating symptom of irritable bowel syndrome (IBS), a disorder affecting up to 30% of adults. A better understanding of the mechanisms underlying visceral hypersensitivity may facilitate development of more targeted therapies, improving the quality of life of these individuals. The studies performed in this thesis were designed to investigate important factors of visceral pain, including early-life manipulations, genetic predisposition and sex hormones. Maternal separation (MS) consistently reproduces visceral hypersensitivity and altered anxiety-like behaviours in rats, symptoms associated with IBS. It has been found that 5-HT2B receptor antagonism blocks visceral pain but no difference in relative 5-HT2B receptor mRNA expression was found in hippocampus, amygdala and colon. The neuronal activation patterns of prefrontal cortex and amygdala of MS rats were then investigated. MS animals are characterised by differential activation of the prefrontal cortex (anterior cingulate cortex (ACC), infralibic cortex, prelimbic cortex) as well as the central nucleus of the amygdala (CeA). Genetic factors also contribute to pain syndromes such as IBS. We utilised the Wistar Kyoto (WKY) rat, a stress-sensitive strain, as an animal model of brain-gut axis dysfunction. WKY rats have a lower expression of the glutamate transporter EAAT2 and mGlu4 receptor in the ACC. Another early-life factor that can increase susceptibility to functional gastrointestinal symptoms later life is disruption of the gut microbiota, thus early-life antibiotic treatment was used to assess this effect. Antibiotic treatment induced visceral hypersensitivity in adulthood and may be related to observed reductions in spinal cord alpha-2A adrenoreceptor (adra2A) mRNA. Lastly, we investigated sex differences in visceral sensitivity. EAAT1 & 2 mRNA levels are lower in females, potentially increasing glutamatergic concentration at the symaptic level. Moreover, NR1 and NR2B subunits mRNA of NMDA receptor were increased in caudal ACC of females. These findings may account for sex differences in visceral sensitivity.

Immune and stress factors in the pathophysiology of the mdx mouse model of Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) is a fatal multi-system neuromuscular disease caused by loss of dystrophin. The loss of dystrophin from membranes of contractile muscle cells and the dysregulation of the DAPC, induces chronic inflammation due to tissue necrosis and eventual replacement with collagen which weakens muscular force and strength. Dystrophin deficiency may cause under-diagnosed features of DMD include mood disorders such as depression and anxiety and dysfunction of the gastrointestinal tract. The first study in the thesis examined mood in the dystrophin-deficient mdx mouse model of DMD and examined the effects of the tri-cyclic antidepressant, amitriptyline on behaviours. Amitriptyline had anti-depressant and anxiolytic effects in the mdx mice possibly through effects on stress factors such as corticotrophin-releasing factor (CRF). This antidepressant also reduced skeletal muscle inflammation and caused a reduction in circulating interleukin (IL)-6 levels. In the second and third studies, we specifically blocked IL-6 signalling and used Urocortin 2, CRFR2 agonist to investigate their potential as therapeutic targets in mdx mice pathophysiology. Isometric and isotonic contractile properties of the diaphragm, were compared in mdx mice treated with anti IL-6 receptor antibodies (anti IL-6R) and/or Urocortin 2. Deficits in force production, work and power detected in mdx mice were improved with treatment. In study three I investigated contractile properties in gastrointestinal smooth muscle. As compared to wild type mice, mdx mice had slower faecal transit times, shorter colons with thickened muscle layers and increased contractile activity in response to recombinant IL-6. Blocking IL-6 signalling resulted in an increase in colon length, normalised faecal output times and a reduction in IL-6-evoked contractile activity. The findings from these studies indicate that for both diaphragm and gastrointestinal function in a dystrophin-deficient model, targeting of IL-6 and CRFR2 signalling has beneficial therapeutic effects.

Multi-parametric metabolic assessment of cells under stress conditions

Glycolysis, glutaminolysis, the Krebs cycle and oxidative phosphorylation are the main metabolic pathways. Exposing cells to key metabolic substrates (glucose, glutamine and pyruvate); investigation of the contribution of substrates in stress conditions such as uncoupling and hypoxia was conducted. Glycolysis, O2 consumption, O2 and ATP levels and hypoxia inducible factor (HIF) signalling in PC12 cells were investigated. Upon uncoupling with FCCP mitochondria were depolarised similarly in all cases, but a strong increase in respiration was only seen in the cells fed on glutamine with either glucose or pyruvate. Inhibition of glutaminolysis reversed the glutamine dependant effect. Differential regulation of the respiratory response to FCCP by metabolic environment suggests mitochondrial uncoupling has a potential for substrate-specific inhibition of cell function. At reduced O2 availability (4 % and 0 % O2), cell bioenergetics and local oxygenation varied depending on the substrate composition. Results indicate that both supply and utilisation of key metabolic substrates can affect the pattern of HIF-1/2α accumulation by differentially regulating iO2¬, ATP levels and Akt/Erk/AMPK pathways. Inhibition of key metabolic pathways can modulate HIF regulatory pathways, metabolic responses and survival of cancer cells in hypoxia. Hypoxia leads to transcriptional activation, by HIF, of pyruvate dehydrogenase (PDH) kinase which phosphorylates and inhibits PDH, a mitochondrial enzyme that converts pyruvate into acetyl-CoA. The levels of PDH (total and phosphorylated), PDH kinase and HIF-1α were analysed in HCT116 and HCT116 SCO2-/- (deficient in complex IV of the respiratory chain) grown under 20.9 % and 3 % O2. Data indicate that regulation of PDH can occur in a manner independent of the HIF-1/PDH kinase 1 axis, mitochondrial respiration and the demand for acetyl-CoA. Collectively these results can be applied to many diseases; reduced nutrient supply and O2 during ischemia/stroke, hypoglycaemia in diabetes mellitus and cancer associated changes in uncoupling protein expression levels.

The effects of osmotic stress on the structure and function of the cell nucleus.

Osmotic stress is a potent regulator of the normal function of cells that are exposed to osmotically active environments under physiologic or pathologic conditions. The ability of cells to alter gene expression and metabolic activity in response to changes in the osmotic environment provides an additional regulatory mechanism for a diverse array of tissues and organs in the human body. In addition to the activation of various osmotically- or volume-activated ion channels, osmotic stress may also act on the genome via a direct biophysical pathway. Changes in extracellular osmolality alter cell volume, and therefore, the concentration of intracellular macromolecules. In turn, intracellular macromolecule concentration is a key physical parameter affecting the spatial organization and pressurization of the nucleus. Hyper-osmotic stress shrinks the nucleus and causes it to assume a convoluted shape, whereas hypo-osmotic stress swells the nucleus to a size that is limited by stretch of the nuclear lamina and induces a smooth, round shape of the nucleus. These behaviors are consistent with a model of the nucleus as a charged core/shell structure pressurized by uneven partition of macromolecules between the nucleoplasm and the cytoplasm. These osmotically-induced alterations in the internal structure and arrangement of chromatin, as well as potential changes in the nuclear membrane and pores are hypothesized to influence gene transcription and/or nucleocytoplasmic transport. A further understanding of the biophysical and biochemical mechanisms involved in these processes would have important ramifications for a range of fields including differentiation, migration, mechanotransduction, DNA repair, and tumorigenesis.

Neuroprotection resulting from insufficiency of RANBP2 is associated with the modulation of protein and lipid homeostasis of functionally diverse but linked pathways in response to oxidative stress.

Oxidative stress is a deleterious stressor associated with a plethora of disease and aging manifestations, including neurodegenerative disorders, yet very few factors and mechanisms promoting the neuroprotection of photoreceptor and other neurons against oxidative stress are known. Insufficiency of RAN-binding protein-2 (RANBP2), a large, mosaic protein with pleiotropic functions, suppresses apoptosis of photoreceptor neurons upon aging and light-elicited oxidative stress, and promotes age-dependent tumorigenesis by mechanisms that are not well understood. Here we show that, by downregulating selective partners of RANBP2, such as RAN GTPase, UBC9 and ErbB-2 (HER2; Neu), and blunting the upregulation of a set of orphan nuclear receptors and the light-dependent accumulation of ubiquitylated substrates, light-elicited oxidative stress and Ranbp2 haploinsufficiency have a selective effect on protein homeostasis in the retina. Among the nuclear orphan receptors affected by insufficiency of RANBP2, we identified an isoform of COUP-TFI (Nr2f1) as the only receptor stably co-associating in vivo with RANBP2 and distinct isoforms of UBC9. Strikingly, most changes in proteostasis caused by insufficiency of RANBP2 in the retina are not observed in the supporting tissue, the retinal pigment epithelium (RPE). Instead, insufficiency of RANBP2 in the RPE prominently suppresses the light-dependent accumulation of lipophilic deposits, and it has divergent effects on the accumulation of free cholesterol and free fatty acids despite the genotype-independent increase of light-elicited oxidative stress in this tissue. Thus, the data indicate that insufficiency of RANBP2 results in the cell-type-dependent downregulation of protein and lipid homeostasis, acting on functionally interconnected pathways in response to oxidative stress. These results provide a rationale for the neuroprotection from light damage of photosensory neurons by RANBP2 insufficiency and for the identification of novel therapeutic targets and approaches promoting neuroprotection.

Latent factor analysis to discover pathway-associated putative segmental aneuploidies in human cancers.

Tumor microenvironmental stresses, such as hypoxia and lactic acidosis, play important roles in tumor progression. Although gene signatures reflecting the influence of these stresses are powerful approaches to link expression with phenotypes, they do not fully reflect the complexity of human cancers. Here, we describe the use of latent factor models to further dissect the stress gene signatures in a breast cancer expression dataset. The genes in these latent factors are coordinately expressed in tumors and depict distinct, interacting components of the biological processes. The genes in several latent factors are highly enriched in chromosomal locations. When these factors are analyzed in independent datasets with gene expression and array CGH data, the expression values of these factors are highly correlated with copy number alterations (CNAs) of the corresponding BAC clones in both the cell lines and tumors. Therefore, variation in the expression of these pathway-associated factors is at least partially caused by variation in gene dosage and CNAs among breast cancers. We have also found the expression of two latent factors without any chromosomal enrichment is highly associated with 12q CNA, likely an instance of "trans"-variations in which CNA leads to the variations in gene expression outside of the CNA region. In addition, we have found that factor 26 (1q CNA) is negatively correlated with HIF-1alpha protein and hypoxia pathways in breast tumors and cell lines. This agrees with, and for the first time links, known good prognosis associated with both a low hypoxia signature and the presence of CNA in this region. Taken together, these results suggest the possibility that tumor segmental aneuploidy makes significant contributions to variation in the lactic acidosis/hypoxia gene signatures in human cancers and demonstrate that latent factor analysis is a powerful means to uncover such a linkage.

Epigenetic regulation of the nitrosative stress response and intracellular macrophage survival by extraintestinal pathogenic Escherichia coli.

Extraintestinal pathogenic Escherichia coli (ExPEC) reside in the enteric tract as a commensal reservoir, but can transition to a pathogenic state by invading normally sterile niches, establishing infection and disseminating to invasive sites like the bloodstream. Macrophages are required for ExPEC dissemination, suggesting the pathogen has developed mechanisms to persist within professional phagocytes. Here, we report that FimX, an ExPEC-associated DNA invertase that regulates the major virulence factor type 1 pili (T1P), is also an epigenetic regulator of a LuxR-like response regulator HyxR. FimX regulated hyxR expression through bidirectional phase inversion of its promoter region at sites different from the type 1 pili promoter and independent of integration host factor (IHF). In vitro, transition from high to low HyxR expression produced enhanced tolerance of reactive nitrogen intermediates (RNIs), primarily through de-repression of hmpA, encoding a nitric oxide-detoxifying flavohaemoglobin. However, in the macrophage, HyxR produced large effects on intracellular survival in the presence and absence of RNI and independent of Hmp. Collectively, we have shown that the ability of ExPEC to survive in macrophages is contingent upon the proper transition from high to low HyxR expression through epigenetic regulatory control by FimX.

In situ concentration of semi-volatile aerosol using water-condensation technology

The effect of concentrating semi-volatile aerosols using a water-condensation technology was investigated using the Versatile Aerosol Concentration Enrichment System (VACES) and the Aerodyne Aerosol Mass Spectrometer (AMS) during measurements of ambient aerosol in Pittsburgh, PA. It was found that the shape of the sulfate mass-weighed size distribution was approximately preserved during passage through the concentrator for all the experiments performed, with a mass enhancement factor of about 10-20 depending on the experiment. The size distributions of organics, ammonium and nitrate were preserved on a relatively clean day (sulfate concentration around 7μg/m3), while during more polluted conditions the concentration of these compounds, especially nitrate, was increased at small sizes after passage through the concentrator. The amount of the extra material, however, is rather small in these experiments: between 2.4% and 7.5% of the final concentrated PM mass is due to "artifact" condensation. An analysis of thermodynamic processes in the concentrator indicates that the extra particle material detected can be explained by redistribution of gas-phase material to the aerosol phase in the concentrator. The analysis shows that the condensation of extra material is expected to be larger for water-soluble semi-volatile material, such as nitrate, which agrees with the observations. The analysis also shows that artifact formation of nitrate will be more pronounced in ammonia-limited conditions and virtually undetectable in ammonia-rich conditions. © 2004 Elsevier Ltd. All rights reserved.