Trigger Factors (trigger + factor)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Trigger Factor and DnaK possess overlapping substrate pools and binding specificities

MOLECULAR MICROBIOLOGY, Issue 5 2003
Elke Deuerling
Summary Ribosome-associated Trigger Factor (TF) and the DnaK chaperone system assist the folding of newly synthesized proteins in Escherichia coli. Here, we show that DnaK and TF share a common substrate pool in vivo. In TF-deficient cells, ,tig, depleted for DnaK and DnaJ the amount of aggregated proteins increases with increasing temperature, amounting to 10% of total soluble protein (approximately 340 protein species) at 37°C. A similar population of proteins aggregated in DnaK depleted tig+ cells, albeit to a much lower extent. Ninety-four aggregated proteins isolated from DnaK- and DnaJ-depleted ,tig cells were identified by mass spectrometry and found to include essential cytosolic proteins. Four potential in vivo substrates were screened for chaperone binding sites using peptide libraries. Although TF and DnaK recognize different binding motifs, 77% of TF binding peptides also associated with DnaK. In the case of the nascent polypeptides TF and DnaK competed for binding, however, with competitive advantage for TF. In vivo, the loss of TF is compensated by the induction of the heat shock response and thus enhanced levels of DnaK. In summary, our results demonstrate that the co-operation of the two mechanistically distinct chaperones in protein folding is based on their overlap in substrate specificities. [source]


Structures of and interactions between domains of trigger factor from Thermotoga maritima

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2007
Erik Martinez-Hackert
Trigger factor (TF) is a eubacterial chaperone that associates with ribosomes at the peptide-exit tunnel and also occurs in excess free in the cytosol. TF is a three-domain protein that appears to exist in a dynamic equilibrium of oligomerization states and interdomain conformations. X-ray crystallography and chemical cross-linking were used to study the roles of the N- and C-terminal domains of Thermotoga maritima TF in TF oligomerization and chaperone activity. The structural conservation of both the N- and C-terminal TF domains was unambiguously established. The biochemical and crystallographic data reveal a tendency for these domains to partake in diverse and apparently nonspecific protein,protein interactions. It is found that the T. maritima and Escherichia coli TF surfaces lack evident exposed hydrophobic patches. Taken together, these data suggest that TF chaperones could interact with nascent proteins via hydrophilic surfaces. [source]


Eczematous reactions to food in atopic eczema: position paper of the EAACI and GA2LEN

ALLERGY, Issue 7 2007
T. Werfel
Food allergy and atopic eczema (AE) may occur in the same patient. Besides typical immediate types of allergic reactions (i.e. noneczematous reactions) which are observed in patients suffering from AE, it is clear that foods, such as cow's milk and hen's eggs, can directly provoke flares of AE, particularly in sensitized infants. In general, inhaled allergens and pollen-related foods are of greater importance in older children, adolescents and adults. Clinical studies have revealed that more than 50% of affected children with AE that can be exacerbated by certain foods will react with a worsening of skin eczema either alone or in addition to immediate symptoms. Adolescents and adults may also react to foods, but reactions to ,classical' food allergens, such as hen's eggs and cow's milk, are not as common as in childhood. Some patients with AE do react to pollen-associated foods. Food-induced eczema should not be neglected by the allergologist: On the one hand, food can be a relevant trigger factor of persistent moderate-to-severe AE; on the other hand, unnecessary diets which are not based on a proper diagnosis may lead to malnutrition and additional psychological stress on patients suffering from AE. Eczematous reactions to food can only be diagnosed by a thorough diagnostic procedure, taking into account the patient's history, the degree of sensitization and the clinical relevance of the sensitization. The latter has often to be proven by oral food challenges. Upon oral food challenge it is most important to evaluate the status of the skin with an established score (e.g. SCORAD, EASI) after 24 h and later because otherwise worsening of eczema will be missed. [source]


Confined dynamics of a ribosome-bound nascent globin: Cone angle analysis of fluorescence depolarization decays in the presence of two local motions

PROTEIN SCIENCE, Issue 10 2009
Jamie P. Ellis
Abstract We still know very little about how proteins achieve their native three-dimensional structure in vitro and in the cell. Folding studies as proteins emerge from the mega Dalton-sized ribosome pose special challenges due to the large size and complicated nature of the ribosome-nascent chain complex. This work introduces a combination of three-component analysis of fluorescence depolarization decays (including the presence of two local motions) and in-cone analysis of diffusive local dynamics to investigate the spatial constraints experienced by a protein emerging from the ribosomal tunnel. We focus on E. coli ribosomes and an all-,-helical nascent globin in the presence and absence of the cotranslationally active chaperones DnaK and trigger factor. The data provide insights on the dynamic nature and structural plasticity of ribosome-nascent chain complexes. We find that the sub-ns motions of the N-terminal fluorophore, reporting on the globin dynamics in the vicinity of the N terminus, are highly constrained both inside and outside the ribosomal tunnel, resulting in high-order parameters (>0.85) and small cone semiangles (<30°). The shorter globin chains buried inside the tunnel are less spatially constrained than those of a reference sequence from a natively unfolded protein, suggesting either that the two nascent chain sequences have a different secondary structure and therefore sample different regions of the tunnel or that the tunnel undergoes local structural adjustments to accommodate the globin sequence. Longer globins emerging out of the ribosomal tunnel are also found to have highly spatially constrained slow (ns) motions. There are no observable spectroscopic changes in the absence of bound chaperones. [source]


Structures of and interactions between domains of trigger factor from Thermotoga maritima

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2007
Erik Martinez-Hackert
Trigger factor (TF) is a eubacterial chaperone that associates with ribosomes at the peptide-exit tunnel and also occurs in excess free in the cytosol. TF is a three-domain protein that appears to exist in a dynamic equilibrium of oligomerization states and interdomain conformations. X-ray crystallography and chemical cross-linking were used to study the roles of the N- and C-terminal domains of Thermotoga maritima TF in TF oligomerization and chaperone activity. The structural conservation of both the N- and C-terminal TF domains was unambiguously established. The biochemical and crystallographic data reveal a tendency for these domains to partake in diverse and apparently nonspecific protein,protein interactions. It is found that the T. maritima and Escherichia coli TF surfaces lack evident exposed hydrophobic patches. Taken together, these data suggest that TF chaperones could interact with nascent proteins via hydrophilic surfaces. [source]


GENERAL PRACTITIONERS LEAVING RURAL PRACTICE IN WESTERN VICTORIA

AUSTRALIAN JOURNAL OF RURAL HEALTH, Issue 2 2000
Peter MacIsaac
ABSTRACT The West Vic Division of General Practice, working with the Department of General Practice, The University of Queensland conducted a qualitative study of GPs who had left western Victoria over the previous 10 years to examine issues relating to the decision to leave rural practice. This study was conducted as part of a project to explore the role of rural Divisions in assisting with general practitioner recruitment and retention. The study supported the conclusions of a similar study in North Queensland and proposed a model that regards rural retention as an interplay of influences both positive and negative with acute trigger factors that can precipitate the decision to leave. Conflict and dissatisfaction with aspects of rural GP hospital work appeared to be a relatively frequent trigger factor that is immediately amenable to intervention from Divisions of general practice and through improvement in negotiation and conflict resolution skills for rural general practitioners. [source]


Cytoplasmic Overexpression, Folding, and Processing of Penicillin Acylase Precursor in Escherichiacoli

BIOTECHNOLOGY PROGRESS, Issue 5 2005
Yali Xu
Penicillin acylase (PAC) precursor, proPAC, was overproduced in a soluble or insoluble form in the cytoplasm of Escherichia coli through the expression of the leader-less pac gene (ll-pac) devoid of the coding region for the signal peptide of PAC. Also, a portion of the overexpressed proPAC was further processed to form mature PAC, indicating that the posttranslational processing steps for PAC maturation can occur in both the periplasm and the cytoplasm of E.coli. The cultivation performance for ll-pac expression was limited by several factors, including (1) misfolding of proPAC, resulting in the aggregation of insoluble proPAC as inclusion bodies, (2) intracellular proteolysis, leading to the degradation of the overexpressed gene products, and (3) inefficient PAC maturation, limiting the formation of active PAC. The effect of coexpression of various cytoplasmic chaperones, including trigger factor, GroEL/ES, DnaK/J-GrpE, and their combinations, on ll-pac expression was investigated. Intracellular proteolysis of the overexpressed gene products could be prevented by coexpression of GroEL/ES. On the other hand, coexpression of trigger factor appeared to be able to facilitate the folding of soluble proPAC and to improve PAC maturation. The roles of trigger factor and GroEL/ES could be coordinated to significantly improve ll-pac expression performance. DnaK/J-GrpE had an effect for solublization of proPAC and perhaps, similar to trigger factor, for improving PAC maturation. The ll-pac expression performance was also significantly improved through the simultaneous coexpression of DnaK/J-GrpE and GroEL/ES. The results of the study suggest that the folding and/or processing of proPAC could be a major issue limiting the overproduction of PAC in E. coli and the bottleneck could be eliminated through the coexpression of appropriate chaperone(s). [source]


Fungal rDNA signatures in coronary atherosclerotic plaques

ENVIRONMENTAL MICROBIOLOGY, Issue 12 2007
Stephan J. Ott
Summary Bacterial DNA has been found in coronary plaques and it has therefore been concluded that bacteria may play a role as trigger factors in the chronic inflammatory process underlying coronary atherosclerosis. However, the microbial spectrum is complex and it is not known whether microorganisms other than bacteria are involved in coronary disease. Fungal 18S rDNA signatures were systematically investigated in atherosclerotic tissue obtained through catheter-based atherectomy of 38 patients and controls (unaffected coronary arteries) using clone libraries, denaturating gradient gel analysis (DGGE), in situ hybridization and fluorescence in situ hybridization (FISH). Fungal DNA was found in 35 of 38 (92.11%) coronary heart disease patients by either polymerase chain reaction (PCR) with universal primers or in situ hybridization analysis (n = 5), but not in any control sample. In a clone library with more than 350 sequenced clones from pooled patient DNA, an overall richness of 19 different fungal phylotypes could be observed. Fungal profiles of coronary heart disease patients obtained by DGGE analysis showed a median richness of fungal species of 5 (range from 2 to 9) with a high interindividual variability (mean similarity 18.83%). For the first time, the presence of fungal components in atherosclerotic plaques has been demonstrated. Coronary atheromatous plaques harbour diverse and variable fungal communities suggesting a polymicrobial contribution to the chronic inflammatory aetiology. [source]


Increased levels of serum IL-31 in chronic spontaneous urticaria,

EXPERIMENTAL DERMATOLOGY, Issue 5 2010
Ulrike Raap
Please cite this paper as: Increased levels of serum IL-31 in chronic spontaneous urticaria. Experimental Dermatology 2010; 19: 464,466. Abstract:, IL-31 represents a novel cytokine involved in pruritic skin diseases including atopic dermatitis (AD). We, therefore, aimed at investigating IL-31 levels in chronic spontaneous urticaria (CU). We included 46 patients with CU, 26 non-atopic skin healthy subjects as negative and 28 patients with AD as positive controls. IL-31 serum levels were analysed using commercial ELISA kit. IL-31 serum levels were higher in patients with CU compared to healthy controls (P < 0.001), but lower compared to patients with AD (P < 0.001). There was no difference in IL-31 serum levels in autologous serum skin test positive or negative CU patients and patients with infectious trigger factors including helicobacter pylori infection. IL-31 serum levels may play a role in the pathophysiology of CU. This is supported by the finding that not all patients with CU respond to antihistamine treatment but to the treatment with immunosuppressive drugs. [source]


How Children and Parents Evaluate the Headache Centre's Intervention

HEADACHE, Issue 2 2009
Anna Ferrari MD
Background., While adult headache patients' satisfaction with treatments has been widely investigated, less attention has been paid to children and adolescent headache patients' opinions and their parents' views. Objective., The aim of our follow-up survey was to analyze the outcomes of the Headache Centre's intervention and the evolution of headache according to patients until the age of 16 and their parents. Methods., We studied all outpatients suffering from episodic primary headache according to International Classification of Headache Disorders 2nd edition criteria, seen for the first time in 2005-2006 at the Headache Centre of the University Hospital of Modena (Italy), and at least one of their parents. The duration of the follow-up ranged from 1 to 3 years. For the purpose of the study, a specific questionnaire was created and administered by a telephone interview. Results., We enrolled 84 patients (38 females, 45%; 46 males, 55%; mean age ± SD: 12.9 ± 2.9 years) with primary headache: migraine without aura 66%, episodic tension-type headache 23%, migraine with aura 11%. At the follow-up, 70% of the patients reported that headache had improved; frequency had decreased significantly more than severity (P = .000, Fisher's exact test), both in those who had followed a prophylactic treatment and in those who had not. A high percentage of the children and parents could precisely indicate trigger factors for headache: especially excessive worrying and studying. The patients reporting an improvement attributed it to pharmacological prophylactic treatment, but also to other factors: first of all, better school results and more happiness than before. Seventy-seven percent of the parents thought that the Headache Centre's intervention had helped them to better understand and manage their children's headache. Conclusions., Children's and adolescents' headache has in most cases a favorable prognosis; the Headache Centre's intervention is considered effective by most parents. We must increase and focus therapeutic efforts addressed to the few patients with worsening headaches in spite of treatment, since these children's/adolescents' headache also is at risk to progress in the adult age. [source]


Gender Differences in Treatment-Seeking Chronic Headache Sufferers

HEADACHE, Issue 7 2001
Dawn A. Marcus MD
Objective.,To identify gender differences within a group of patients seeking treatment for chronic headache. Previous studies of the general population have reported differences in headache symptoms, frequency, disability, and psychological distress, with women affected with more severe and disabling symptoms than men. This study evaluated these features in a population seeking treatment. Methods.,Two hundred fifty-eight consecutive patients with headache attending a university headache clinic were evaluated with questionnaires about headache symptoms and psychological distress. Comparisons between men and women were made for headache symptoms, severity, frequency, trigger factors, comorbid depression and anxiety, and response to treatment. Results.,There were no gender differences in headache symptoms, frequency, severity, and duration. Headache triggers were gender-specific, with men more likely to endorse exercise and women more likely to endorse stress and exposure to odors. Psychological comorbidity was similar among men and women seeking treatment, with a mean Beck Depression Inventory score of 10 and a mean Spielberger trait anxiety score of 39 for both men and women. Disability was greater in men, with 46% reporting restrictions in activities more than 3 days per week because of headache compared with 29% of women. In addition, men were more likely to contribute headache control to external figures than women. Conclusions.,Patients seeking treatment for chronic headache do not have the same gender-specific differences that have been reported in general population surveys. Men who seek treatment for headache are more likely to have significant disability, and are equally likely to have symptoms of depression and anxiety as women who seek treatment. Clinical and research investigations of headache triggers need to be gender-specific. [source]


Viral exanthems in childhood , infectious (direct) exanthems.

JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 4 2009
Part 1: Classic exanthems
Summary Exanthems during childhood occur quite often and are mostly harmless in nature. Among different trigger factors, viruses are of prime importance. Viral exanthems may manifest as a macular, maculopapular, papular, urticarial or vesicular rash. Exanthems with other causes (bacterial toxins, drugs, autoimmune diseases) as well as those with unclear etiology such as unilateral lat-erothoracic exanthem or Kawasaki disease must be differentiated from viral exanthems. This review focuses on the classic viral exanthems. [source]


Functional symptoms confused with allergic disorders in children and adolescents

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 5 2002
Bodo Niggemann
The diagnosis of a functional respiratory disorder is sometimes difficult and time-consuming, because the symptoms often resemble those of organic diseases. The most common entities are hyperventilation syndrome, psychogenic cough, sighing dyspnea, and vocal cord dysfunction. Typical signs are heavy breathing or dyspnea, cough or sneezing, various breathing sounds, tightness of the throat or chest, pain, and fear. Criteria for differentiation include the lack of nocturnal symptoms, the sudden occurrence, no typical trigger factors, the variable duration, a quick regression, and that symptoms do not respond to adequate pharmacotherapy and finally normal results of diagnostic work-up. Therapeutic options comprise psychological intervention (by reassurance, relaxation techniques, and behaviour therapy) and physiotherapy (e.g. breathing therapy, voice training). Intensive efforts should be made to diagnose functional symptoms at an early stage because this will prevent stigmatization and fixation of symptoms and disease, and also prevent children from undergoing unnecessary and potentially harmful therapies. [source]


GENERAL PRACTITIONERS LEAVING RURAL PRACTICE IN WESTERN VICTORIA

AUSTRALIAN JOURNAL OF RURAL HEALTH, Issue 2 2000
Peter MacIsaac
ABSTRACT The West Vic Division of General Practice, working with the Department of General Practice, The University of Queensland conducted a qualitative study of GPs who had left western Victoria over the previous 10 years to examine issues relating to the decision to leave rural practice. This study was conducted as part of a project to explore the role of rural Divisions in assisting with general practitioner recruitment and retention. The study supported the conclusions of a similar study in North Queensland and proposed a model that regards rural retention as an interplay of influences both positive and negative with acute trigger factors that can precipitate the decision to leave. Conflict and dissatisfaction with aspects of rural GP hospital work appeared to be a relatively frequent trigger factor that is immediately amenable to intervention from Divisions of general practice and through improvement in negotiation and conflict resolution skills for rural general practitioners. [source]


Leukotrienes and other mast cell mediators cause asthmatic airway obstruction

CLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 2004
S.-E. Dahlén
Summary From an evolutionary perspective, bronchoconstriction is a highly conserved mechanism for defence against stimuli that are noxious for the lung and airways. The presence of mast cells in all layers of the airways makes them ideally situated to function as sensors of environmental changes that require such a host defence reaction. In addition to being activated by high affinity IgE receptors, many other trigger factors are known to activate signal transduction pathways leading to mast cell degranulation. This includes changes in the physical and chemical composition of the environment, exposure to endotoxin and other microbial factors acting on Toll-like receptors [1], intake of certain drugs and in particular virtually all nonsteroidal anti-inflammatory drugs (NSAIDs) in subjects with the peculiar syndrome aspirin-intolerant asthma (AIA) [2]. Irrespective of the trigger, the consequence of mast cell activation is release of biologically active smooth muscle stimulating mediators as well as the secretion of cytokines, chemotactic factors and enzymes that are believed to trigger further cascades contributing to long-term tissue remodelling and chronic airway inflammation. [source]