612 research outputs found

    Studies on the cell-free biosynthesis of β-lactam antibiotics

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    Genetic Studies of Sulfadiazine-resistant and Methionine-requiring \u3cem\u3eNeisseria\u3c/em\u3e Isolated From Clinical Material

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    Deoxyribonucleate (DNA) preparations were extracted from Neisseria meningitidis (four isolates from spinal fluid and blood) and N. gonorrhoeae strains, all of which were resistant to sulfadiazine upon primary isolation. These DNA preparations, together with others from in vitro mutants of N. meningitidis and N. perflava, were examined in transformation tests by using as recipient a drug-susceptible strain of N. meningitidis (Ne 15 Sul-s Met+) which was able to grow in a methionine-free defined medium. The sulfadiazine resistance typical of each donor was introduced into the uniform constitution of this recipient. Production of p-aminobenzoic acid was not significantly altered thereby. Transformants elicited by DNA from the N. meningitidis clinical isolates were resistant to at least 200 μg of sulfadiazine/ml, and did not show a requirement for methionine (Sul-r Met+). DNA from six strains of N. gonorrhoeae, which were isolated during the period of therapeutic use of sulfonamides, conveyed lower degrees of resistance and, invariably, a concurrent methionine requirement (Sul-r/Met−). The requirement of these transformants, and that of in vitro mutants selected on sulfadiazine-agar, was satisfied by methionine, but not by vitamin B12, homocysteine, cystathionine, homoserine, or cysteine. Sul-r Met+ and Sul-r/Met− loci could coexist in the same genome, but were segregated during transformation. On the other hand, the dual Sul-r/Met− properties were not separated by recombination, but were eliminated together. DNA from various Sul-r/Met− clones tested against recipients having nonidentical Sul-r/Met− mutant sites yielded Sul-s Met+ transformants. The met locus involved is genetically complex, and will be a valuable tool for studies of genetic fine structure of members of Neisseria, and of genetic homology between species

    Prediction of setup times for an advanced upper limb functional electrical stimulation system

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    Introduction: Rehabilitation devices take time to don, and longer or unpredictable setup time impacts on usage. This paper reports on the development of a model to predict setup time for upper limb functional electrical stimulation. Methods: Participants’ level of impairment (Fugl Meyer-Upper Extremity Scale), function (Action Research Arm Test) and mental status (Mini Mental Scale) were measured. Setup times for each stage of the setup process and total setup times were recorded. A predictive model of setup time was devised using upper limb impairment and task complexity. Results: Six participants with stroke were recruited, mean age 60 (�17) years and mean time since stroke 9.8 (�9.6) years. Mean Fugl Meyer-Upper Extremity score was 31.1 (�6), Action Research Arm Test 10.4 (�7.9) and Mini Mental Scale 26.1 (�2.7). Linear regression analysis showed that upper limb impairment and task complexity most effectively predicted setup time (51% as compared with 39%) (F(2,21) ¼ 12.782, adjusted R2 ¼ 0.506; p<.05). Conclusions: A model to predict setup time based on upper limb impairment and task complexity accounted for 51% of the variation in setup time. Further studies are required to test the model in real-world settings and to identify other contributing factors

    N-gram analysis of 970 microbial organisms reveals presence of biological language models

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    <p>Abstract</p> <p>Background</p> <p>It has been suggested previously that genome and proteome sequences show characteristics typical of natural-language texts such as "signature-style" word usage indicative of authors or topics, and that the algorithms originally developed for natural language processing may therefore be applied to genome sequences to draw biologically relevant conclusions. Following this approach of 'biological language modeling', statistical n-gram analysis has been applied for comparative analysis of whole proteome sequences of 44 organisms. It has been shown that a few particular amino acid n-grams are found in abundance in one organism but occurring very rarely in other organisms, thereby serving as genome signatures. At that time proteomes of only 44 organisms were available, thereby limiting the generalization of this hypothesis. Today nearly 1,000 genome sequences and corresponding translated sequences are available, making it feasible to test the existence of biological language models over the evolutionary tree.</p> <p>Results</p> <p>We studied whole proteome sequences of 970 microbial organisms using n-gram frequencies and cross-perplexity employing the Biological Language Modeling Toolkit and Patternix Revelio toolkit. Genus-specific signatures were observed even in a simple unigram distribution. By taking statistical n-gram model of one organism as reference and computing cross-perplexity of all other microbial proteomes with it, cross-perplexity was found to be predictive of branch distance of the phylogenetic tree. For example, a 4-gram model from proteome of <it>Shigellae flexneri 2a</it>, which belongs to the <it>Gammaproteobacteria </it>class showed a self-perplexity of 15.34 while the cross-perplexity of other organisms was in the range of 15.59 to 29.5 and was proportional to their branching distance in the evolutionary tree from <it>S. flexneri</it>. The organisms of this genus, which happen to be pathotypes of <it>E.coli</it>, also have the closest perplexity values with <it>E. coli.</it></p> <p>Conclusion</p> <p>Whole proteome sequences of microbial organisms have been shown to contain particular n-gram sequences in abundance in one organism but occurring very rarely in other organisms, thereby serving as proteome signatures. Further it has also been shown that perplexity, a statistical measure of similarity of n-gram composition, can be used to predict evolutionary distance within a genus in the phylogenetic tree.</p

    Treatment Burden and Chronic Illness: Who is at Most Risk?

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    Background: There is a need to ascertain the type and level of treatment burden experienced by people with co-morbidities. This is important to identify the characteristics of participants who are at most risk of treatment burden.  Objective: The aim of this study is to identify the characteristics of participants who are at most risk of treatment burden.  Methods: This cross-sectional study was part of a larger project and recruitment was conducted across four Australian regions: rural, semi-rural and metropolitan. Participants were asked about their treatment burden using an adapted version of a measure, which included the following five dimensions: medication, time and administrative, lifestyle change, social life and financial burden.  Results: In total, 581 participants with various chronic health conditions reported a mean global treatment burden of 56.5 out of 150 (standard deviation = 34.5). Number of chronic conditions (β = .34, p < 0.01), age, (β = −.27, p < 0.01), the presence of an unpaid carer (β = .22, p < 0.001) and the presence of diabetes mellitus and other endocrine conditions (β = .13, p < 0.01) were significant predictors of overall treatment burden. For the five dimensions of treatment burden, social, medicine and administrative burden were predicted by the same cluster of variables: number of conditions, age, presence of an unpaid carer and diabetes. However, in addition to these variables, financial dimensions were also predicted by education level, ethnicity and health insurance. Educational level also influenced lifestyle burden.  Conclusion: A substantial proportion of community-dwelling adults with chronic conditions have considerable levels of treatment burden. Specifically, health professionals should provide greater focus on managing overall treatment burden for persons who are of young age, have an endocrine condition or an unpaid carer, or a combination of these factors

    Recombinant family 3 carbohydrate-binding module as a new additive for enhanced enzymatic saccharification of whole slurry from autohydrolyzed eucalyptus globulus wood

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    By-products resulting from lignocellulosics pretreatment affect the digestibility of resulting whole slurries, but this can be minimized by additives supplementation. In this work, a family 3 carbohydrate-binding module (CBM3), recombinantly produced from Escherichia coli, was used as additive in the enzymatic hydrolysis of the whole slurry from autohydrolyzed Eucalyptus globulus wood (EGW). At the higher dosage used (30 mg/gsolids), CBM3 led to an increase in glucose yield from 75 to 89%. A similar result was obtained for bovine serum albumin (BSA) (11% increase), which has a well-documented additive effect. CBM3 had no effect on the non-productive binding of enzymes, since it could not bind to EGW lignin, while it rapidly bound to cellulose, as shown by fluorescence microscopy. CBM3 is a valid additive for enhanced lignocellulosic saccharification and a valuable alternative to costly additives (e.g. polyethylene glycol) as it can be affordably produced from heterologous bacterium, thus contributing to more cost-efficient biomass valorization bioprocesses.This work was developed under the strategic funding of UID/BIO/04469/2013 unit, COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020—Programa Operacional Regional do Norte. The research leading to the reported results has received funding from Fundação para a Ciência e a Tecnologia (FCT) through the project MultiBiorefinery (POCI-01–0145-FEDER-016403) and through grants to C. Oliveira (SFRH/BPD/110640/2015) and D. Gomes (SFRH/BD/88623/2012).info:eu-repo/semantics/publishedVersio

    Comparative Genome Analysis Reveals an Absence of Leucine-Rich Repeat Pattern-Recognition Receptor Proteins in the Kingdom Fungi

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    Background: In plants and animals innate immunity is the first line of defence against attack by microbial pathogens. Specific molecular features of bacteria and fungi are recognised by pattern recognition receptors that have extracellular domains containing leucine rich repeats. Recognition of microbes by these receptors induces defence responses that protect hosts against potential microbial attack. Methodology/Principal Findings: A survey of genome sequences from 101 species, representing a broad cross-section of the eukaryotic phylogenetic tree, reveals an absence of leucine rich repeat-domain containing receptors in the fungal kingdom. Uniquely, however, fungi possess adenylate cyclases that contain distinct leucine rich repeat-domains, which have been demonstrated to act as an alternative means of perceiving the presence of bacteria by at least one fungal species. Interestingly, the morphologically similar osmotrophic oomycetes, which are taxonomically distant members of the stramenopiles, possess pattern recognition receptors with similar domain structures to those found in plants. Conclusions: The absence of pattern recognition receptors suggests that fungi may possess novel classes of patternrecognition receptor, such as the modified adenylate cyclase, or instead rely on secretion of anti-microbial secondary metabolites for protection from microbial attack. The absence of pattern recognition receptors in fungi, coupled with their abundance in oomycetes, suggests this may be a unique characteristic of the fungal kingdom rather than a consequence o
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