Recruitment and retention in psychiatry.
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Education, Medical, Graduate↗
Biomedical subjects
J Sauer
Publications and source records attributed to J Sauer.
Stability and function of interdomain linker variants of glucoamylase 1 from Aspergillus niger.
Several variants of glucoamylase 1 (GA1) from Aspergillus niger were created in which the highly O-glycosylated peptide (aa 468--508) connecting the (alpha/alpha)(6)-barrel catalytic domain and the starch binding domain was substituted at the gene level by equivalent segments of glucoamylases from Hormoconis resinae, Humicola grisea, and Rhizopus oryzae encoding 5, 19, and 36 amino acid residues. Variants were constructed in which the H. resinae linker was elongated by proline-rich sequences as this linker itself apparently was too short to allow formation of the corresponding protein variant. Size and isoelectric point of GA1 variants reflected differences in linker length, posttranslational modification, and net charge. While calculated polypeptide chain molecular masses for wild-type GA1, a nonnatural proline-rich linker variant, H. grisea, and R. oryzae linker variants were 65,784, 63,777, 63,912, and 65,614 Da, respectively, MALDI-TOF-MS gave values of 82,042, 73,800, 73,413, and 90,793 Da, respectively, where the latter value could partly be explained by an N-glycosylation site introduced near the linker C-terminus. The k(cat) and K(m) for hydrolysis of maltooligodextrins and soluble starch, and the rate of hydrolysis of barley starch granules were essentially the same for the variants as for wild-type GA1. beta-Cyclodextrin, acarbose, and two heterobidentate inhibitors were found by isothermal titration calorimetry to bind to the catalytic and starch binding domains of the linker variants, indicating that the function of the active site and the starch binding site was maintained. The stability of GA1 linker variants toward GdnHCl and heat, however, was reduced compared to wild-type.
Amino Acid Sequence↗
Protection against murine listeriosis by oral vaccination with recombinant Salmonella expressing hybrid Yersinia type III proteins.
In the present study, we have investigated the possibility to engage the Yersinia outer protein E (YopE) as a carrier molecule for heterologous Ag delivery by the type III secretion system of Salmonella typhimurium. Defined secretion and translocation domains of YopE were fused to the immunodominant T cell Ags listeriolysin O and p60 of Listeria monocytogenes. In vitro experiments showed that S. typhimurium allows secretion and translocation of large hybrid YopE proteins in a type III-dependent fashion. Translocation and cytosolic delivery of these chimeric proteins into host cells, but not secretion into endosomal compartments, led to efficient MHC class I-restricted Ag presentation of listerial nonamer peptides. Mice orally vaccinated with a single dose of attenuated S. typhimurium expressing translocated hybrid YopE proteins revealed high numbers of IFN-gamma-producing cells reactive with listeriolysin O 91-99 or p60 217-225, respectively. This CD8 T cell response protected mice against a challenge with L. monocytogenes. In conclusion, these findings suggest that YopE is a versatile carrier molecule for type III-mediated foreign Ag delivery by Salmonella vaccine strains.
Administration, Oral↗
Nitrogen starvation-induced chlorosis in Synechococcus PCC 7942. Low-level photosynthesis as a mechanism of long-term survival.
Cells of the non-diazotrophic cyanobacterium Synechococcus sp. strain PCC 7942 acclimate to nitrogen deprivation by differentiating into non-pigmented resting cells, which are able to survive prolonged periods of starvation. In this study, the physiological properties of the long-term nitrogen-starved cells are investigated in an attempt to elucidate the mechanisms of maintenance of viability. Preservation of energetic homeostasis is based on a low level of residual photosynthesis; activities of photosystem II and photosystem I were approximately 0.1% of activities of vegetatively growing cells. The low levels of photosystem I activity were measured by a novel colorimetric assay developed from the activity staining of ferredoxin:NADP+ oxidoreductase. Photosystem II reaction centers, as determined by chlorophyll fluorescence measurements, exhibited normal properties, although the efficiency of light harvesting was significantly reduced compared with that of control cells. Long-term chlorotic cells carried out protein synthesis at a very low, but detectable level, as revealed by in vivo [35S]methionine labeling and two-dimensional gel electrophoresis. In conjunction with the very low levels of total cellular protein contents, this implies a continuous protein turnover during chlorosis. Synthesis of components of the photosynthetic apparatus could be detected, whereas factors of the translational machinery were stringently down-regulated. Beyond the massive loss of protein during acclimation to nitrogen deprivation, two proteins that were identified as SomA and SomB accumulated due to an induced expression following nitrogen reduction.
Amino Acid Sequence↗
Increased first-contact rates for very-late-onset schizophrenia-like psychosis in African- and Caribbean-born elders.
BACKGROUND: Studies have consistently shown a higher incidence of schizophrenia with onset in early adult life in African and Caribbean migrants to the UK. AIMS: To establish the incidence (first-contact rates) of very-late-onset (>60 years) schizophrenia-like psychosis (SLP) in south London and to test the hypothesis that this is higher among African- and Caribbean-born than indigenous elders. METHOD: We identified all new referrals of SLP to the Maudsley Hospital between 1995 and 2000. Demographic details, including age, ethnicity and electoral ward (address), were obtained from case notes. Incidence was estimated using 1997 census data to determine the denominator population for each ethnic group. RESULTS: The incidence of SLP was significantly higher in African- and Caribbean-born than indigenous elders: 172.4 per 100,000 population (95% CI=57.9--286.8) in African- and Caribbean-born males and 323.5 per 100,000 population (95% CI 167.8--479.1) in African- and Caribbean-born females. Rates also were increased in elders from other immigrant groups, but the numbers involved were too small to reach accepted levels of significance. CONCLUSIONS: Large-scale epidemiological studies are needed to determine both the incidence of and the coexistent risk factors for SLP among all elderly migrants, who may constitute a group with high service needs.
Africa↗
Glucoamylase: structure/function relationships, and protein engineering.
Glucoamylases are inverting exo-acting starch hydrolases releasing beta-glucose from the non-reducing ends of starch and related substrates. The majority of glucoamylases are multidomain enzymes consisting of a catalytic domain connected to a starch-binding domain by an O-glycosylated linker region. Three-dimensional structures have been determined of free and inhibitor complexed glucoamylases from Aspergillus awamori var. X100, Aspergillus niger, and Saccharomycopsis fibuligera. The catalytic domain folds as a twisted (alpha/alpha)(6)-barrel with a central funnel-shaped active site, while the starch-binding domain folds as an antiparallel beta-barrel and has two binding sites for starch or beta-cyclodextrin. Certain glucoamylases are widely applied industrially in the manufacture of glucose and fructose syrups. For more than a decade mutational investigations of glucoamylase have addressed fundamental structure/function relationships in the binding and catalytic mechanisms. In parallel, issues of relevance for application have been pursued using protein engineering to improve the industrial properties. The present review focuses on recent findings on the catalytic site, mechanism of action, substrate recognition, the linker region, the multidomain architecture, the engineering of specificity and stability, and roles of individual substrate binding subsites.
Amino Acid Sequence↗
Q-switch laser and tattoo pigments: first results of the chemical and photophysical analysis of 41 compounds.
BACKGROUND AND OBJECTIVE: In the Western world, there are at least 20-30 million people with tattoos. Improved self-image and social stigmatization are the main reasons for removing tattoos from skin. Q-switched lasers are applied to destroy the tattoo compounds in the skin. The treatment of tattoos containing ink often gives excellent results, whereas the results of treatments for coloured tattoos are not predictable and usually are worse. The chemical structure and the absorption spectra of the tattoo pigments are usually unknown. However, the efficacy of the treatment by using light of different Q-switched lasers (wavelengths 510, 532, 694, 755, 1064 nm) is correlated to both the chemical structure of the tattooed compounds yielding specific absorption spectra and the laser wavelength used. STUDY DESIGN/MATERIALS AND METHODS: A structural and spectroscopic analysis of 41 coloured pigments was performed. RESULTS: The 41 substances were identified, and they consist of 16 individual chemicals of different structured well-known industrial organic pigments. The absorption spectra of the 16 pigments were measured quantitatively. CONCLUSION: The results of the present analysis explain to some extent the outcome of clinical studies regarding laser therapy of coloured tattoos. Because the laser energy used produces a high temperature in the azo or polycyclic pigments, it is necessary to investigate whether that change causes possibly toxic or cancerogenic compounds.
Coloring Agents↗
[Adenocarcinoma in a tail-gut cyst: a rare cause of recurrent perianal fistula].
A 58-year-old woman was initially externally diagnosed in 1983 with a presacral mass, which was subsequently treated as an abscess. Thereafter, the patient experienced recurrent perianal fistulas. Further diagnostic studies revealed a cystic tumor, considered to be an epidermoid cyst, which was located in the inferior pelvis and was consequently removed. Histologically, cystic scar tissue was found with a highly differentiated adenocarcinoma which measured 4 cm. Later on, the patient again experienced perianal fistulas originating from a renewed presacral mass. As a result, an abdominal-perianal rectum extirpation and a partial resection of the sacrum with placement of a descendostomy were done. Histologically, adenocarcinoma tissue was found at the base of a tail-gut cyst. One year following her operation, the patient is free from any complaints and relapses. The tail-gut cyst is a very rare entity which arises from the inadequate involution of the tail-gut during embryonal development. A malignant transformation occurs in 10% of the cases. In the case of recurrent perianal fistulas and cystic masses between the rectum and os sacrum or os coccygeum, a tail-gut cyst should be taken into consideration, the goal being its complete removal.
Adenocarcinoma↗
Prospective memory: a secondary task with promise.
This paper examines the utility of prospective memory as a secondary task. For this purpose, the results of seven experiments were analysed to evaluate the sensitivity of prospective memory, making a direct comparison with another secondary task (reaction time). Both tasks were used as subsidiary elements in a complex task environment, the design of which was based on the micro-world research paradigm. The results indicated that prospective memory was slightly more vulnerable to variations in experimental conditions than was reaction time. The paper concludes that, overall, prospective memory appears to be a suitable secondary task. This is partly attributed to the element of self-initiation, which is a feature of some prospective memory tasks. It is recommended to use time-based and pulse-based prospective memory tasks since they seem to be the more sensitive.
Humans↗
The use of micro-worlds for human factors research in extended spaceflight.
This article provides an analysis of the utility of micro-worlds for human factors research in extended spaceflight. It outlines potential areas of application of the micro-world research paradigm in the context of spaceflight. While the research literature provides several examples of micro-worlds that simulate different work environments of high complexity, little work has been done with this tool in the operational environment of spaceflight. The author presents a micro-world, called CAMS, that has been especially developed for use in space-related research. The results from a research programme (comprising seven studies using CAMS) are presented. Based on a comparative analysis of the benefits and limitations of micro-worlds compared to other simulation types, the author argues that micro-worlds can be a very effective tool, provided their inherent limitations are taken into consideration.
Astronauts↗
A conceptual framework for designing micro-worlds for complex work domains: a case study of the Cabin Air Management System.
A conceptual framework for the design of micro-worlds is presented in this paper. This is illustrated by a micro-world, called Cabin Air Management System (CAMS), that has been used in a research program to investigate human behavior during work with complex systems. Although CAMS is based on the operational context of spaceflight, its underlying principles correspond to a process control task. The authors propose a theoretical framework for micro-world design, which was used to guide the development of the CAMS micro-world. This may provide a helpful guideline for researchers wishing to develop a micro-world by using a more structured approach. A detailed technical description of CAMS is given to demonstrate the kind of real-world scenarios that may be simulated with this task environment. Finally, general aspects of the utility of micro-world research are discussed.
Air Conditioning↗
Effects of training on short- and long-term skill retention in a complex multiple-task environment.
The paper reports the results of an experiment on the performance and retention of a complex task. This was a computer-based simulation of the essential elements of a spacecraft's life support system. It allowed the authors to take a range of measures, including primary and secondary task performance, system intervention and information sampling strategies, mental model structure, and subjective operator state. The study compared the effectiveness of two methods of training, based on low level (procedure-based) and high level (system-based) understanding. Twenty-five participants were trained extensively on the task, then given a 1-h testing session. A second testing session was carried out 8 months after the first (with no intervening practice) with 17 of the original participants. While training had little effect on control performance, there were considerable effects on system management strategies, as well as in structure of operator's mental model. In the second testing session, the anticipated general performance decrement did not occur, though for complex faults there was an increase in selectivity towards the primary control task. The relevance of the findings for training and skill retention in real work environments is discussed in the context of a model of compensatory control.
Adult↗
The Synechococcus strain PCC 7942 glnN product (glutamine synthetase III) helps recovery from prolonged nitrogen chlorosis.
We report the cloning and sequencing of the glnN gene encoding a class III glutamine synthetase from the cyanobacterium Synechococcus strain PCC 7942. Mapping of the transcriptional start site revealed a DNA sequence in the promoter region that resembles an imperfect NtcA binding motif. Expression of glnN is impaired in NtcA- and P(II)-deficient mutants. The only parameter which was negatively affected in the glnN mutant compared to the wild type was the recovery rate of prolonged nitrogen-starved cells with low concentrations of combined nitrogen.
Bacterial Proteins↗
PACT to the future.
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Community Health Services↗
[Conservative and surgical antireflux therapy as prevention of carcinoma].
INTRODUCTION: Based on findings in literature, the effectiveness of the medical versus operative antireflux therapy was examined as a prophylaxis to impede the formation of an adenocarcinoma in the case of Barrett esophagus. MEDICAL ANTIREFLUX THERAPY: Despite reports of success following the administration of Omeprazole, the inhibition of acid secretion does not lead to the regression of the endobrachyesophagus for most patients. The partial shortening of the Barrett segment is reported in up to 78% of cases, however the precancerous changes of the distal esophagus are not eliminated. In spite of medical therapy with proton pump inhibitors, up to 6% of dysplasias become metaplasias per year. In 3% of the patients, an adenocarcinoma arises. OPERATIVE ANTIREFLUX THERAPY: It is reported in the literature that there is a partial regression of the endobrachyesophagus in up to 34% of cases and complete regression in up to 11% of cases following operative antireflux therapy. Despite a macroscopically unchanged Barrett segment following a fundoplication or semifundoplication procedure, a complete regression of minor dysplasias and the complete regression of intestinal metaplasias is possible. In only 30% of patients, postoperative atypical findings were ascertainable. Nevertheless, a severe change can appear in the cylinder epithelium of the remaining Barrett segment following an operative antireflux therapy, up to the formation of an adenocarcinoma (1-9%). For this reason, the patients must be endoscopically and histologically examined at regular intervals following the antireflux operation. CONCLUSION: In the case of evidence of severe dysplasias in the Barrett segment, the attempt at carcinoma prophylaxis by means of antireflux therapy is no longer indicated. With the appearance of mild dysplasias and complete intestinal metaplasias in the Barrett esophagus, an antireflux operation can lead to a reduction in the grade of atypical cells. In cases of existing metaplasia or the presence of mild dysplasias, the administration of proton pump inhibitors or H2 blockers is only indicated as a symptomatic therapy.
Adenocarcinoma↗
[Littoral-cell angioma--a rare differential diagnosis on splenic tumors].
UNLABELLED: HISTORY AND PRE-ADMISSION FINDINGS: Routine abdominal sonography of a 51-year-old man 6 years after removal of the right testis and radiotherapy for a seminoma revealed a 3 cm mass within the spleen. INVESTIGATIONS: All biochemical tests were normal. Computed tomography (CT) and magnetic resonance imaging confirmed the tumour which had not been present on the CT before the seminoma had been treated. No other space-occupying lesions were found in the thorax and abdomen. TREATMENT AND COURSE: A splenectomy was performed because a metachronous metastasis of the seminoma was suspected. The operation and subsequent course were uneventful. At operation the tumour had been diagnosed as an haemangioma because of its gross appearance, but histological and immunohistochemical examination revealed a littoral cell angioma. CONCLUSION: The littoral cell angioma is a benign vascular lesion in the red pulp of the spleen, which may be caused by different stimuli such as chronic infection or tumours. This case illustrates, that this tumour should be considered in the differential diagnosis of an unclear neoplasm in the spleen.
Diagnosis, Differential↗
[26-year-old patient with cutaneous leishmaniasis and an initial diabetes mellitus manifestation].
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Adult↗
Nitrogen starvation in synechococcus PCC 7942: involvement of glutamine synthetase and NtcA in phycobiliprotein degradation and survival
The nondiazotrophic cyanobacterium Synechococcus sp. strain PCC 7942 responds to nitrogen deprivation by differentiating into nonpigmented resting cells able to survive prolonged periods of starvation. The degradation of photosynthetic pigments, termed chlorosis, proceeds in an ordered manner in which the light-harvesting phycobiliproteins are degraded prior to chlorophyll. Here, we show that the function of the global transcription activator of nitrogen-regulated genes, NtcA, is required for the sequential pigment degradation and cell survival. The P(II) protein, known to signal the nitrogen status of the cells, is most probably not involved in the perception of the nitrogen-starvation-specific signal since in a mutant lacking P(II), chlorosis proceeded in the same manner as in the wild type. Inhibition of glutamine synthetase with l-methionine sulfoximine led to a rapid decrease of apc mRNA and to an increase of nblA mRNA levels, which is characteristic for nitrogen deprivation, suggesting that nitrogen starvation is sensed by a metabolic signal connected to glutamine synthetase activity. However, l-methionine sulfoximine treatment did not induce phycobiliprotein degradation, but led to an immediate cessation of this proteolytic process after its induction by nitrogen deprivation. This suggests that the proteolytic activity elicited by the expression of nblA has to be supported by glutamine synthetase activity.
Journal Article↗