54 research outputs found

    Downregulation of a CYP74 Rubber Particle Protein Increases Natural Rubber Production in \u3ci\u3eParthenium argentatum\u3c/i\u3e

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    We report functional genomics studies of a CYP74 rubber particle protein from Parthenium argentatum, commonly called guayule. Previously identified as an allene oxide synthase (AOS), this CYP74 constitutes the most abundant protein found in guayule rubber particles. Transgenic guayule lines with AOS gene expression down-regulated by RNAi (AOSi) exhibited strong phenotypes that included agricultural traits conducive to enhancing rubber yield. AOSi lines had higher leaf and stem biomass, thicker stembark tissues, increased stem branching and improved net photosynthetic rate. Importantly, the rubber content was significantly increased in AOSi lines compared to the wild-type (WT), vector control and AOS overexpressing (AOSoe) lines, when grown in controlled environments both in tissue-culture media and in greenhouse/growth chambers. Rubber particles from AOSi plants consistently had less AOS particle-associated protein, and lower activity (for conversion of 13-HPOT to allene oxide). Yet plants with downregulated AOS showed higher rubber transferase enzyme activity. The increase in biomass in AOSi lines was associated with not only increases in the rate of photosynthesis and non-photochemical quenching (NPQ), in the cold, but also in the content of the phytohormone SA, along with a decrease in JA, GAs, and ABA. The increase in biosynthetic activity and rubber content could further result from the negative regulation of AOS expression by high levels of salicylic acid in AOSi lines and when introduced exogenously. It is apparent that AOS in guayule plays a pivotal role in rubber production and plant growth

    A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis

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    BACKGROUND: Linezolid is an effective, but toxic anti-tuberculosis drug that is currently recommended for the treatment of drug-resistant tuberculosis. Improved oxazolidinones should have a better safety profile, while preserving efficacy. Delpazolid is a novel oxazolidinone developed by LegoChem Biosciences Inc. that has been evaluated up to phase 2a clinical trials. Since oxazolidinone toxicity can occur late in treatment, LegoChem Biosciences Inc. and the PanACEA Consortium designed DECODE to be an innovative dose-ranging study with long-term follow-up for determining the exposure-response and exposure-toxicity relationship of delpazolid to support dose selection for later studies. Delpazolid is administered in combination with bedaquiline, delamanid and moxifloxacin. METHODS: Seventy-five participants with drug-sensitive, pulmonary tuberculosis will receive bedaquiline, delamanid and moxifloxacin, and will be randomized to delpazolid dosages of 0 mg, 400 mg, 800 mg, 1200 mg once daily, or 800 mg twice daily, for 16 weeks. The primary efficacy endpoint will be the rate of decline of bacterial load on treatment, measured by MGIT liquid culture time to detection from weekly sputum cultures. The primary safety endpoint will be the proportion of oxazolidinone class toxicities; neuropathy, myelosuppression, or tyramine pressor response. Participants who convert to negative liquid media culture by week 8 will stop treatment after the end of their 16-week course and will be observed for relapse until week 52. Participants who do not convert to negative culture will receive continuation phase treatment with rifampicin and isoniazid to complete a six-month treatment course. DISCUSSION: DECODE is an innovative dose-finding trial, designed to support exposure-response modelling for safe and effective dose selection. The trial design allows assessment of occurrence of late toxicities as observed with linezolid, which is necessary in clinical evaluation of novel oxazolidinones. The primary efficacy endpoint is the change in bacterial load, an endpoint conventionally used in shorter dose-finding trials. Long-term follow-up after shortened treatment is possible through a safety rule excluding slow-and non-responders from potentially poorly performing dosages. TRIAL REGISTRATION: DECODE was registered in ClinicalTrials.gov before recruitment start on 22 October 2021 (NCT04550832)

    Time-to-Positivity of Blood Cultures in Children With Sepsis.

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    <b>Background:</b> Blood cultures are essential for the diagnosis and further appropriate treatment in children with suspected sepsis. In most hospitals, children will be empirically treated or closely monitored for at least 48 h awaiting results of blood cultures. Several studies have challenged the optimal duration of empiric treatment in the era of continuously monitored blood culture systems. The aim of our study was to investigate time-to-positivity (TTP) of blood cultures in children with proven sepsis. <b>Methods:</b> The Swiss Pediatric Sepsis Study prospectively enrolled children 0-16 years of age with blood culture positive sepsis between September 2011 and October 2015. TTP was prospectively assessed in six participating academic pediatric hospitals by fully automated blood culture systems. <b>Results:</b> In 521 (93%) of 562 bacteremia episodes (493 children, median age 103 days, range 0 days-16.9 years) a valid TTP was available. Median TTP was 12 h (IQR 8-17 h, range 0-109 h). By 24, 36, and 48 h, 460 (88%), 498 (96%), and 510 (98%) blood cultures, respectively, were positive. TTP was independent of age, sex, presence of comorbidities, site of infection and severity of infection. Median TTP in all age groups combined was shortest for group B streptococcus (8.7 h) and longest for coagulase-negative staphylococci (16.2 h). <b>Conclusion:</b> Growth of bacteria in blood cultures is detectable within 24 h in 9 of 10 children with blood culture-proven sepsis. Therefore, a strict rule to observe or treat all children with suspected sepsis for at least 48 h is not justified

    Development of DArT marker platforms and genetic diversity assessment of the U.S. collection of the new oilseed crop lesquerella and related species.

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    The advantages of using molecular markers in modern genebanks are well documented. They are commonly used to understand the distribution of genetic diversity in populations and among species which is crucial for efficient management and effective utilization of germplasm collections. We describe the development of two types of DArT molecular marker platforms for the new oilseed crop lesquerella (Physaria spp.), a member of the Brassicaceae family, to characterize a collection in the National Plant Germplasm System (NPGS) with relatively little known in regards to the genetic diversity and traits. The two types of platforms were developed using a subset of the germplasm conserved ex situ consisting of 87 Physaria and 2 Paysonia accessions. The microarray DArT revealed a total of 2,833 polymorphic markers with an average genotype call rate of 98.4% and a scoring reproducibility of 99.7%. On the other hand, the DArTseq platform developed for SNP and DArT markers from short sequence reads showed a total of 27,748 high quality markers. Cluster analysis and principal coordinate analysis indicated that the different accessions were successfully classified by both systems based on species, by geographical source, and breeding status. In the germplasm set analyzed, which represented more than 80% of the P. fendleri collection, we observed that a substantial amount of variation exists in the species collection. These markers will be valuable in germplasm management studies and lesquerella breeding, and augment the microsatellite markers previously developed on the taxa

    Lesquerella growth and selenium uptake affected by saline irrigation water composition

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    Abstract A greenhouse study was conducted to determine the effects of waters differing in salt composition on growth and selenium (Se) accumulation by lesquerella (Lesquerella fendleri Gray S. Wats.). Plants were established by direct seeding into sand cultures and irrigated with solutions containing either (a) Cl − as the dominant anion or (b) a mixture of salts of SO 4 2 − and Cl − . Four treatments of each salinity type were imposed. Electrical conductivities of the irrigation waters were 1.7, 4, 8, and 13 dS m − 1 . Two months after salinization, Se (l mg l − 1 , 12.7 mM) was added to all solutions as Na 2 SeO 4 . Shoot growth was significantly reduced by increasing Cl-salinity. Regardless of salinity type, concentrations of Ca 2 + , Mg 2 + , Cl − , total-S, and Se were higher in the leaves than the stems, whereas K + and Na + were higher in the stem. Leaf-Se concentrations were not significantly affected by Cl-based irrigation waters, averaging 503 mg Se kg − 1 dry wt across salinity levels, whereas leaf-Se decreased consistently and significantly from 218 to 13 mg kg − 1 as mixed salt salinity increased. The dramatic reduction in Se was attributed to SO 4 2 − :SeO 4 2 − competition during plant uptake. The strong Se-accumulating ability of lesquerella suggests that the crop should be further evaluated as a potentially valuable phytoremediator of Se-contaminated soils and waters of low to moderate salinity in areas where the dominant anion in the substrate is Cl − . Published by Elsevier Science B.V

    Mycoplasma pneumoniae detection in children with respiratory tract infections and influence on management – a retrospective cohort study in Switzerland

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    Aim To evaluate the frequency of Mycoplasma pneumoniae in nasopharyngeal specimens from children with respiratory tract infections (RTIs) and to detail clinical characteristics and management. Methods The study was designed as a retrospective cohort study. All children with RTI and nucleic acid amplification testing from nasopharyngeal specimens were analysed. Clinical data were extracted from electronic health records for all M. pneumoniae‐positive cases. Stored samples of cases and a random selection of matched controls were retested using a M. pneumoniae‐specific nucleic acid amplification test. Results Of 4460 children, 70 (1.6%) were positive for M. pneumoniae with a median age of 6.4 (IQR: 2.7–9.7). M. pneumoniae was the only organism identified in 50/64 (78%) cases. Macrolide treatment was prescribed in 52/65 (80%); prescription was empirical in 29/52 (56%) and targeted in 23/52 (44%) with no difference regarding patient age, oxygen requirement or duration of hospitalisation. Conclusion The prevalence of M. pneumoniae in nasopharyngeal specimens of children with RTI was low. The detection of M. pneumoniae influenced antibiotic prescriptions, but the benefit of early empirical versus targeted treatment remains unclear

    Plot of Δ<i>K</i> from K = 2 to 7 (a) and the population structure of 75 <i>P. fendleri</i> accessions at <i>K</i> = 4 (b).

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    <p>Plot of Δ<i>K</i> from K = 2 to 7 (a) and the population structure of 75 <i>P. fendleri</i> accessions at <i>K</i> = 4 (b).</p
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