7,733 research outputs found
Causes of Increased Mortality from Hepatocellular Carcinoma in High Incidence Country: The Taiwan Experience
No full textNationwide Hepatitis B Vaccination Program in Taiwan: Effectiveness in 20 years after its launch
No full textThe Seroprevalence of Hepatitis B Viral Markers among Freshmen – 20 Years after Mass Hepatitis B Vaccination Program in Taiwan
No full textThe functionality of telomerase depends on CPF–CF induced 3′end processing of its RNA component TLC1 and a novel Nrd1–Nab3 surveillance mechanism
No full textAbstract Telomere elongation is driven by telomerase, which consists of several proteins and the ncRNA component TLC1 in yeast. While many ncRNAs are terminated via the Nrd1–Nab3–Sen1 (NNS) pathway, we found that TLC1 requires cleavage and polyadenylation factor (CPF)–cleavage factor (CF) mediated 3′end processing and the resulting poly(A) tail to mature into a functional ribozyme. The poly(A) tail is predicted to fold back onto (U)-repeats potentially forming a terminal stem–loop structure that supports Sm-ring binding and thereby re-import into the nucleus after cytoplasmic shuttling. However, longer pre-TLC1 transcripts are predicted to fold differently, resulting in Sm-ring and import receptor binding defects, leaving them unable to overcome this cytoplasmic quality control checkpoint. To prevent cytoplasmic leakage of overlong transcripts, we propose an additional nuclear monitoring system, requiring Nrd1–Nab3 binding sites located between the first PAS motifs. CPF–CF formation might compete with Nrd1–Nab3 releasing them from shorter but not from longer transcripts facilitating their decay. This potential competitive RNA-binding of CPF–CF and Nrd1–Nab3 balances stability and decay
Phosphorylation and proteome dynamics in pathogen-resistant tomato plants
No full textMicrobial plant pathogens impose a continuous threat on global food production. Similar to disease resistance in mammals, an innate immune system allows plants to recognise pathogens and swiftly activate defence. For the work described in this thesis, the interaction between tomato and the extracellular fungal pathogen Cladosporium fulvum serves as a model system to study host resistance and susceptibility in plant-pathogen interactions. Resistance to C. fulvum in tomato plants follows the gene-for-gene hypothesis, which requires the presence of a Cf resistance gene in tomato and presence of the cognate avirulence gene (Avr) in C. fulvum. Upon perception of the Avr by a tomato plant, a typical hypersensitive response (HR) is induced that renders the plant resistant to C. fulvum. In the years preceding this thesis work, most research was focussed on understanding which Avrs are produced by C. fulvum and how these Avrs are actually perceived by resistant plants (Chapter 1). The goal of the work described in this thesis is to reveal downstream signalling cascades triggered upon Avr perception. Therefore, the HR was studied by using a model system in which the Cf-4 protein of tomato and the Avr4 protein from C. fulvum were simultaneously expressed in tomato seedlings. Since the Cf-4/Avr-induced responses are inhibited at 33°C and high humidity, these Cf-4/Avr4 seedlings initiate a synchronized and reproducible HR after incubation at 33°C and a subsequent shift to 20°C, which allows studying downstream responses. To prevent pathogen proliferation in the resistant plant, defence signalling cascades need to be activated extremely fast upon pathogen recognition. Therefore, many downstream signalling cascades depend on post-translational modifications (PTMs) that allow a rapid, reversible, controlled and highly specific transduction of perceived signals. An overview of the various types of PTMs and their role in the resistance response of plants to pathogens is provided in Chapter 2. In addition, examples are provided of successful pathogens that manipulate PTMs. Protein phosphorylation seems to play an important role in the Cf-4/Avr4-triggered HR, since Avr4 perception leads to the specific activation of at least three mitogen-activated protein kinases, LeMPK1, -2 and -3, which requires phosphorylation by an upstream kinase (Chapter 3). Each of these three kinases seems to have a different role in downstream defence signalling, since the kinases were shown to have different phosphorylation specificities and therefore most likely have different downstream target substrates. Furthermore, these kinases appear to play a different role with regard to HR and full resistance to C. fulvum in tomato (Chapter 3). Since protein phosphorylation was shown to play an important role in Cf-4/Avr4-induced defence signalling, the phosphoproteome of Cf-4/Avr4 and control seedlings after HR initiation was studied using a new approach (Chapter 4). This approach led to the identification of 50 phosphoproteins, most of which have not been described in tomato before. Quantification revealed 13 phosphoproteins with an altered abundance in the Cf-4/Avr4 seedlings as compared to the control, which implies HR-induced differential phosphorylation of these proteins. Phosphorylation-mediated regulation of the activity of these proteins pointed to a swift decrease in photosynthetic activity upon HR-initiation, which was confirmed by experiments in which the actual efficiency of the photosynthesis in the Cf-4/Avr4 seedlings was determined upon induction of the HR. Furthermore, a shift from aerobic to anaerobic respiration, which possibly results from oxygen depletion caused by a massive oxidative burst consuming large amounts of oxygen, seems to take place upon initiation of the HR. Finally, differential phosphorylation of the four cytoplasmic isoforms of the Hsp90 chaperone protein was observed, suggesting that they play distinct roles during defence signalling (Chapter 4). In addition to the HR, other associated defence responses are initiated upon recognition of C. fulvum. One of these responses is the secretion of defence-related proteins into the apoplast, which is the environment where C. fulvum operates. Therefore, the dynamics of the apoplastic proteome of resistant, Cf-4-expressing plants and susceptible tomato plants lacking Cf-4, were studied after inoculation with a strain of C. fulvum that secretes Avr4 (Chapter 5). Analysis of the apoplastic proteome revealed a slow accumulation of defence proteins in the apoplast of susceptible plants, which is most likely the result of perception of general elicitors of C. fulvum by tomato. In resistant plants, the same set of proteins accumulates in the apoplast, but this occurs much faster and to higher levels. The accelerated response is caused by the Cf-4/Avr4-initiated HR that also leads to cell death. The HR, in combination with the accelerated protein secretion, renders the plants resistant to C. fulvum. In addition, in susceptible plants C. fulvum seems to specifically downregulate genes encoding cell wall proteins of which the accumulation possibly hampers nutrient and water uptake and thereby proliferation of the pathogen in the tomato apoplast. Possibly, an effector of C. fulvum targets a receptor for general elicitors, thereby suppressing transcription of these genes (Chapter 5). Most data described in this thesis have been obtained from Cf-4/Avr4 seedlings in which the HR can be inhibited by incubating the plants at 33°C. The present data suggest that this temperature-sensitivity occurs at the site of signal perception. Possibly, cytoplasmic Hsp90 stabilizes R protein complexes localized at the plasma membrane. Upon high temperature stress, an increased demand for Hsp90 occurs in the cells to stabilize unfolding proteins that play a role in basal cellular processes, which could lead to the release and subsequent degradation of R protein complexes, rendering defence signalling temperature-sensitive (Chapter 6). The temperature-sensitivity of the Cf-4/Avr4-initiated HR provides a very clean and reproducible tool to study the HR, in the absence of the fungus that produces the Avr. Furthermore, the data described in this thesis provide evidence that the Cf-4/Avr4 seedlings recover from the temperature stress before the specific Cf-4/Avr4-triggered HR is initiated. The possibility to separate the events directly associated with the HR from the full resistance response of the plant to the invading fungus, provides new insight into the complexity of plant defence responses and their specific suppression upon successful colonization by C. fulvum (Chapter 6). Comparison of the defence response to other processes that occur in the cell underlines that resistance and HR execution cannot be seen as an independent and separate process in resistant plants that have recognized a pathogen. On the contrary, signalling cascades seem to depend on similar components and on cascades that possibly converge, eventually leading to a similar response (Chapter 6). Finally, an up to date model for the Cf-4/Avr4-triggered HR and resistance is proposed, based on data that have been published before and the results obtained with the research described in this thesis (Chapter 6). <br/
The influence of fiber-matrix adhesion on the linear viscoelastic creep behavior of CF/PPS composites
No full textThe influence of fiber-matrix adhesion on the linear viscoelastic creep behavior of as received and surface modified carbon fiber (AR-CF and SM-CF, respectively) reinforced polyphenylene sulfide (PPS) composite materials was investigated. Short-term tensile creep tests were performed on ±45° specimens under four different isothermal condition; 70, 80, 90 and 100°C. As a preliminary step to obtain the time-temperature master curve, as well as to characterize the changes in matrix dominated properties over storage time, physical aging effects were evaluated on both systems using the short-term test method established by Struik. The results showed that the surface treatment carried out in the SM-CF improved fiber-matrix adhesion, enhancing the mechanical performance of CF/PPS composites but with minor effects on the creep response. Increasing retardation times with physical aging was observed in all test conditions. Compared to temperature effects, physical aging showed to have a small contribution on the creep behavior of CF/PPS composites.Aerospace Structures & MaterialsAerospace Engineerin
Macrorheology of cystic fibrosis, chronic obstructive pulmonary disease & normal sputum
Full text linkAbstract Background Prior microrheologic assessments of selected, microlitre plugs of cystic fibrosis (CF) sputum suggest no intrinsic rheologic abnormality. However, such analyses may not be representative of CF sputum as a whole. We therefore reassessed this question using whole sputum macrorheology. Additionally, we wished to further explore the relationships between sputum rheology, inflammation and infection. Methods Dynamic oscillatory macrorheometry was performed on whole expectorated sputum from stable adults with CF (n = 18) and COPD (n = 12) and induced sputum from normal controls (n = 7). Concomitant sputum inflammatory mediator levels were measured in CF and COPD samples. Sputum collected from CF subjects (n = 6) at commencement and completion of intravenous antibiotic therapy for an infective exacerbation was also assessed. Results CF sputum neutrophil elastase activity (NE) was significantly related to degree of sputum purulence (p = 0.049) and correlated significantly with measures of sputum viscoelasticity (r = 0.696, p = 0.008 for storage modulus G' at 9 Hz). There were significant differences in viscoelasticity between subject groups when samples were compared irrespective of appearance/degree of sputum purulence. However, the macrorheology of mucoid CF sputum did not differ from normal sputum (eg median (range) G' at 9 Hz 2.25 (0.79, 3.26) vs 2.04 (1.4,4.6) Pa, p = 1). In contrast, mucoid COPD samples demonstrated significantly greater viscoelasticity (G' at 9 Hz 4.5 (2.4, 23) Pa) than sputum from both CF (p = 0.048) & normal subjects (p = 0.009). Antibiotic therapy during exacerbations was associated with significant reductions in CF sputum viscoelasticity, with mean (SD) G' at 9 Hz decreasing from 28.5 (11.5) Pa at commencement to 6.4 (4.6) Pa on day 7 (p = 0.01). Conclusion The macrorheologic properties of whole, mucoid CF sputum are not different from normal, confirming the results of prior microrheologic studies. Instead, CF sputum viscoelasticity is related to secondary infection, decreases with intravenous antibiotic therapy and correlates with inflammation. In contrast, COPD sputum demonstrates inherently greater viscoelasticity, providing a novel target for potential therapeutic interventions.</p
On the post-impact fatigue behavior and theoretical life prediction of CF/PEEK-titanium hybrid laminates using an energy dissipation approach
No full textThis paper aims to illustrate the effect of the impact damage on fatigue behavior of CF/PEEK-titanium hybrid laminates. To achieve this end, a fatigue life model was proposed to predict the S–N curves of the laminates at various initial impact energy levels and stress ratios based on the energy dissipation approach. The energy dissipation behavior of the laminates during fatigue loading under different experimental conditions was analyzed through a large amount of post-impact fatigue tests, and the correlation between the initial impact damage and the total fatigue dissipation energy was determined. The full-field axial strain distribution of the titanium layer on the impacted side of the laminate was characterized in terms of initial impact energy level and maximum stress using digital image correlation, and then the post-impact fatigue failure mechanism of CF/PEEK-Ti hybrid laminates was summarized. Finally, the validity of the proposed model was verified by fatigue tests under other conditions of stress ratio and impact energy level. It is worth mentioning that the proposed model is also applicable to other types of FMLs, and can accurately predict the residual fatigue life of laminates after impact with only one set of S–N curve data.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Structural Integrity & Composite
The Association between Abnormal Liver Function and Risk Factors of Metabolic Syndrome among Freshmen
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