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A diaphragmatic electrical activity-based optimization strategy during pressure support ventilation improves synchronization but does not impact work of breathing
No full textAbstract
Background
Poor patient-ventilator synchronization is often observed during pressure support ventilation (PSV) and has been associated with prolonged duration of mechanical ventilation and poor outcome. Diaphragmatic electrical activity (Eadi) recorded using specialized nasogastric tubes is a surrogate of respiratory brain stem output. This study aimed at testing whether adapting ventilator settings during PSV using a protocolized Eadi-based optimization strategy, or Eadi-triggered and -cycled assisted pressure ventilation (or PSV
N
) could (1) improve patient-ventilator interaction and (2) reduce or normalize patient respiratory effort as estimated by the work of breathing (WOB) and the pressure time product (PTP).
Methods
This was a prospective cross-over study. Patients with a known chronic pulmonary obstructive or restrictive disease, asynchronies or suspected intrinsic positive end-expiratory pressure (PEEP) who were ventilated using PSV were enrolled in the study. Four different ventilator settings were sequentially applied for 15\ua0minutes (step 1: baseline PSV as set by the clinician, step 2: Eadi-optimized PSV to adjust PS level, inspiratory trigger, and cycling settings, step 3: step 2\u2009+\u2009PEEP adjustment, step 4: PSV
N
). The same settings as step 3 were applied again after step 4 to rule out a potential effect of time. Breathing pattern, trigger delay (T
d
), inspiratory time in excess (T
iex
), pressure-time product (PTP), and work of breathing (WOB) were measured at the end of each step.
Results
Eleven patients were enrolled in the study. Eadi-optimized PSV reduced T
d
without altering T
iex
in comparison with baseline PSV. PSV
N
reduced T
d
and T
iex
in comparison with baseline and Eadi-optimized PSV. Respiratory pattern did not change during the four steps. The improvement in patient-ventilator interaction did not lead to changes in WOB or PTP.
Conclusions
Eadi-optimized PSV allows improving patient ventilator interaction but does not alter patient effort in patients with mild asynchrony.
..
Human disease genomics: from variants to biology
No full textAbstract
We summarize the remarkable progress that has been made in the identification and functional characterization of DNA sequence variants associated with disease
Enhancement of furan aldehydes conversion in Zymomonas mobilis by elevating dehydrogenase activity and cofactor regeneration
No full textAbstract
Background
Furfural and 5-hydroxymethylfurfural (HMF) are the two major furan aldehyde inhibitors generated from lignocellulose dilute acid pretreatment which significantly inhibit subsequent microbial cell growth and ethanol fermentation. Zymomonas mobilis is an important strain for cellulosic ethanol fermentation but can be severely inhibited by furfural and (or) HMF. Previous study showed that Z. mobilis contains its native oxidoreductases to catalyze the conversion of furfural and HMF, but the corresponding genes have not been identified.
Results
This study identified a NADPH-dependent alcohol dehydrogenase gene ZMO1771 from Z. mobilis ZM4, which is responsible for the efficient reduction of furfural and HMF. Over-expression of ZMO1771 in Z. mobilis significantly increased the conversion rate to both furfural and HMF and resulted in an accelerated cell growth and improved ethanol productivity in corn stover hydrolysate. Further, the ethanol fermentation performance was enhanced again by co-expression of the transhydrogenase gene udhA with ZMO1771 by elevating the NADPH availability.
Conclusions
A genetically modified Z. mobilis by co-expressing alcohol dehydrogenase gene ZMO1771 with transhydrogenase gene udhA showed enhanced conversion rate of furfural and HMF and accelerated ethanol fermentability from lignocellulosic hydrolysate. The results presented in this study provide an important method on constructing robust strains for efficient ethanol fermentation from lignocellulose feedstock.
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Solid-binding peptides for immobilisation of thermostable enzymes to hydrolyse biomass polysaccharides
No full textAbstract
Background
Solid-binding peptides (SBPs) bind strongly to a diverse range of solid materials without the need for any chemical reactions. They have been used mainly for the functionalisation of nanomaterials but little is known about their use for the immobilisation of thermostable enzymes and their feasibility in industrial-scale biocatalysis.
Results
A silica-binding SBP sequence was fused genetically to three thermostable hemicellulases. The resulting enzymes were active after fusion and exhibited identical pH and temperature optima but differing thermostabilities when compared to their corresponding unmodified enzymes. The silica-binding peptide mediated the efficient immobilisation of each enzyme onto zeolite, demonstrating the construction of single enzyme biocatalytic modules. Cross-linked enzyme aggregates (CLEAs) of enzyme preparations either with or without zeolite immobilisation displayed greater activity retention during enzyme recycling than those of free enzymes (without silica-binding peptide) or zeolite-bound enzymes without any crosslinking. CLEA preparations comprising all three enzymes simultaneously immobilised onto zeolite enabled the formation of multiple enzyme biocatalytic modules which were shown to degrade several hemicellulosic substrates.
Conclusions
The current work introduced the construction of functional biocatalytic modules for the hydrolysis of simple and complex polysaccharides. This technology exploited a silica-binding SBP to mediate effectively the rapid and simple immobilisation of thermostable enzymes onto readily-available and inexpensive silica-based matrices. A conceptual application of biocatalytic modules consisting of single or multiple enzymes was validated by hydrolysing various hemicellulosic polysaccharides
A variant by any name: quantifying annotation discordance across tools and clinical databases
No full textAbstract
Background
Clinical genomic testing is dependent on the robust identification and reporting of variant-level information in relation to disease. With the shift to high-throughput sequencing, a major challenge for clinical diagnostics is the cross-identification of variants called on their genomic position to resources that rely on transcript- or protein-based descriptions.
Methods
We evaluated the accuracy of three tools (SnpEff, Variant Effect Predictor, and Variation Reporter) that generate transcript and protein-based variant nomenclature from genomic coordinates according to guidelines by the Human Genome Variation Society (HGVS). Our evaluation was based on transcript-controlled comparisons to a manually curated set of 126 test variants of various types drawn from data sources, each with HGVS-compliant transcript and protein descriptors. We further evaluated the concordance between annotations generated by Snpeff and Variant Effect Predictor and those in major germline and cancer databases: ClinVar and COSMIC, respectively.
Results
We find that there is substantial discordance between the annotation tools and databases in the description of insertions and/or deletions. Using our ground truth set of variants, constructed specifically to identify challenging events, accuracy was between 80 and 90% for coding and 50 and 70% for protein changes for 114 to 126 variants. Exact concordance for SNV syntax was over 99.5% between ClinVar and Variant Effect Predictor and SnpEff, but less than 90% for non-SNV variants. For COSMIC, exact concordance for coding and protein SNVs was between 65 and 88% and less than 15% for insertions. Across the tools and datasets, there was a wide range of different but equivalent expressions describing protein variants.
Conclusions
Our results reveal significant inconsistency in variant representation across tools and databases. While some of these syntax differences may be clear to a clinician, they can confound variant matching, an important step in variant classification. These results highlight the urgent need for the adoption and adherence to uniform standards in variant annotation, with consistent reporting on the genomic reference, to enable accurate and efficient data-driven clinical care
Molecular dissection of germline chromothripsis in a developmental context using patient-derived iPS cells
No full textAbstract
Background
Germline chromothripsis causes complex genomic rearrangements that are likely to affect multiple genes and their regulatory contexts. The contribution of individual rearrangements and affected genes to the phenotypes of patients with complex germline genomic rearrangements is generally unknown.
Methods
To dissect the impact of germline chromothripsis in a relevant developmental context, we performed trio-based RNA expression analysis on blood cells, induced pluripotent stem cells (iPSCs), and iPSC-derived neuronal cells from a patient with de novo germline chromothripsis and both healthy parents. In addition, Hi-C and 4C-seq experiments were performed to determine the effects of the genomic rearrangements on transcription regulation of genes in the proximity of the breakpoint junctions.
Results
Sixty-seven genes are located within 1\ua0Mb of the complex chromothripsis rearrangements involving 17 breakpoints on four chromosomes. We find that three of these genes ( FOXP1 , DPYD , and TWIST1 ) are both associated with developmental disorders and differentially expressed in the patient. Interestingly, the effect on TWIST1 expression was exclusively detectable in the patient\u2019s iPSC-derived neuronal cells, stressing the need for studying developmental disorders in the biologically relevant context. Chromosome conformation capture analyses show that TWIST1 lost genomic interactions with several enhancers due to the chromothripsis event, which likely led to deregulation of TWIST1 expression and contributed to the patient\u2019s craniosynostosis phenotype.
Conclusions
We demonstrate that a combination of patient-derived iPSC differentiation and trio-based molecular profiling is a powerful approach to improve the interpretation of pathogenic complex genomic rearrangements. Here we have applied this approach to identify misexpression of TWIST1 , FOXP1 , and DPYD as key contributors to the complex congenital phenotype resulting from germline ..
Screening of filamentous fungi for antimicrobial silver nanoparticles synthesis
No full textAbstract
The present work had the goal of screening a batch of 20 fungal strains, isolated from sugar cane plantation soil, in order to identify those capable of biosynthesis of silver nanoparticles. These nanoparticles are known to have a large and effective application in clinical microbiology. Four strains were found to be capable of biosynthesis of silver nanoparticles. The biosynthesised nanoparticles were characterised by UV\u2013vis spectroscopy, scanning electron microscopy, EDX, and XRD. They were found to have an average size of 30\u2013100\ua0nm, a regular round shape, and potential antimicrobial activity against Escherichia coli , Staphylococcus aureus, and Pseudomonas aeruginosa . The antimicrobial activity was found to be directly related to the nanoparticles concentration. Mycogenic synthesis of nanoparticles is a green biogenic process preferable to other alternatives. Because fungi are great producers of extracellular enzymes this process makes scaling-up an easier task with high importance for clinical microbiology on the fight against microbial resistance, as well as for other industrial applications
Oscillation of Runge-Kutta methods for advanced impulsive differential equations with piecewise constant arguments
No full textAbstract
The purpose of this paper is to study oscillation of Runge-Kutta methods for linear advanced impulsive differential equations with piecewise constant arguments. We obtain conditions of oscillation and nonoscillation for Runge-Kutta methods. Moreover, we prove that the oscillation of the exact solution is preserved by the \u3b8 -methods. It turns out that the zeros of the piecewise linear interpolation functions of the numerical solution converge to the zeros of the exact solution. We give some numerical examples to confirm the theoretical results
Solving nonlinear Volterra integro-differential equations of fractional order by using Euler wavelet method
No full textAbstract
In this paper, a wavelet numerical method for solving nonlinear Volterra integro-differential equations of fractional order is presented. The method is based upon Euler wavelet approximations. The Euler wavelet is first presented and an operational matrix of fractional-order integration is derived. By using the operational matrix, the nonlinear fractional integro-differential equations are reduced to a system of algebraic equations which is solved through known numerical algorithms. Also, various types of solutions, with smooth, non-smooth, and even singular behavior have been considered. Illustrative examples are included to demonstrate the validity and applicability of the technique
Effect of Eucalyptus expansion on surface runoff in the central highlands of Ethiopia
No full textAbstract
Introduction
Land use/land cover change can affect the ecological processes of an area such as hydrological cycle. The change in the condition of water resources of an area could be a good indicator of changes in ecosystem function as a result of altered land use/land cover. Eucalyptus expansion in central Ethiopia is one of the recent land use/land cover changes causing controversy on its potential ecological effect. This study was designed to evaluate effects of three adjacent land uses/land covers, i.e. cultivated land, grassland and Eucalyptus woodlot on surface runoff in Meja River watershed, central Ethiopia.
Methods
The rainfall amount at each study catchment was collected using the rain gauge installed to record daily rainfall amount. The three land use/land cover types in each study catchment were selected for comparison as treatments. Four replications of each land use/land cover were used forming a total of 12 runoff plots. The rainfall and runoff data were collected twice a day for 91\ua0days.
Results
The study found that land use/land cover significantly affects surface runoff generated from the plots. Higher runoff was recorded from cultivated land. There was no significant difference on runoff volume between grassland and Eucalyptus woodlot.
Conclusions
This shows that expansion of Eucalyptus on grassland could not have significant impact on surface runoff generation but if planted on previously farmland could reduce surface runoff