SWAT

<p>The first release for the pre-run of the SV-COMP 2024.</p&gt

SWAT

<p>The first release for the pre-run of the SV-COMP 2024.</p&gt

Additional file 1 of Metabolic engineering of Aspergillus niger via ribonucleoprotein-based CRISPR–Cas9 system for succinic acid production from renewable biomass

Additional file 1: Table S1. Strain morphology in succinic acid production. Table S2. The initial and final pH value in the cultures at different cultivation temperatures. Table S3. Genes manipulated in this study using corresponding gRNAs. Table S4. Primers used in this study. Figure S1. Plasmids used in this study

Metabolic engineering of Aspergillus niger via ribonucleoprotein-based CRISPR–Cas9 system for succinic acid production from renewable biomass

Abstract Background Succinic acid has great potential to be a new bio-based building block for deriving a number of value-added chemicals in industry. Bio-based succinic acid production from renewable biomass can provide a feasible approach to partially alleviate the dependence of global manufacturing on petroleum refinery. To improve the economics of biological processes, we attempted to explore possible solutions with a fungal cell platform. In this study, Aspergillus niger, a well-known industrial production organism for bio-based organic acids, was exploited for its potential for succinic acid production. Results With a ribonucleoprotein (RNP)-based CRISPR–Cas9 system, consecutive genetic manipulations were realized in engineering of the citric acid-producing strain A. niger ATCC 1015. Two genes involved in production of two byproducts, gluconic acid and oxalic acid, were disrupted. In addition, an efficient C4-dicarboxylate transporter and a soluble NADH-dependent fumarate reductase were overexpressed. The resulting strain SAP-3 produced 17 g/L succinic acid while there was no succinic acid detected at a measurable level in the wild-type strain using a synthetic substrate. Furthermore, two cultivation parameters, temperature and pH, were investigated for their effects on succinic acid production. The highest amount of succinic acid was obtained at 35 °C after 3 days, and low culture pH had inhibitory effects on succinic acid production. Two types of renewable biomass were explored as substrates for succinic acid production. After 6 days, the SAP-3 strain was capable of producing 23 g/L and 9 g/L succinic acid from sugar beet molasses and wheat straw hydrolysate, respectively. Conclusions In this study, we have successfully applied the RNP-based CRISPR–Cas9 system in genetic engineering of A. niger and significantly improved the succinic acid production in the engineered strain. The studies on cultivation parameters revealed the impacts of pH and temperature on succinic acid production and the future challenges in strain development. The feasibility of using renewable biomass for succinic acid production by A. niger has been demonstrated with molasses and wheat straw hydrolysate

Multivariate GWAS of Alzheimer's disease CSF biomarker profiles implies GRIN2D in synaptic functioning: Summary statistics

Summary statistics for a genome-wide association study (GWAS) of Alzheimer's disease CSF biomarkers principal components (PCs). This dataset accompanies the publication "Multivariate GWAS of Alzheimer’s disease CSF biomarker profiles implies GRIN2D in synaptic functioning". The article is currently in press at Genome Medicine. A link will be provided upon publication, but see the medRxiv preprint in the meantime: Neumann, A., Ohlei, O., Küçükali, F., Bos, I. J., Vos, S., Prokopenko, D., ... & Kristel Sleegers & Lars Bertram. (2022). Multivariate GWAS of Alzheimer’s disease CSF biomarker profiles implies GRIN2D in synaptic functioning. medRxiv, 2022-08. https://doi.org/10.1101/2022.08.02.22278185 A GWAS was performed for five different PC biomarkers. PC1: Tau pathology/degeneration PC2: Aβ Pathology PC3: Injury/inflammation PC4: Non-AD inflammation PC5: Non-AD synaptic functioning Each GWAS was performed in either males and females ("all"), in females only ("female"), or in males only ("male"). In addition, we also ran an interaction model with sex as moderator ("interaction"). Each file includes output of the meta-analysis between the EMIF-AD study and ADNI. The files contain following columns: CHROM: Chromosome POS: Position according to Build 37 ID: Chromosome:Position A1: Effect allele A2: Other allele BETA: Effect of one copy of the effect allele on biomarker PCs in SD. In case of sex interaction, the effect specific to females. SE: Standard Error P: p-value D: Direction in ADNI and EMIF-AD respectively Het: Heterogeneity statistics (I2, and corresponding χ2, degrees of freedom and p-value

Intravascular optical coherence elastography

Optical coherence elastography (OCE), a functional extension of optical coherence tomography (OCT), visualizes tissue strain to deduce the tissue’s biomechanical properties. In this study, we demonstrate intravascular OCE using a 1.1 mm motorized catheter and a 1.6 MHz Fourier domain mode-locked OCT system. We induced an intraluminal pressure change by varying the infusion rate from the proximal end of the catheter. We analysed the pixel-matched phase change between two different frames to yield the radial strain. Imaging experiments were carried out in a phantom and in human coronary arteries in vitro. At an imaging speed of 3019 frames/s, we were able to capture the dynamic strain. Stiff inclusions in the phantom and calcification in atherosclerotic plaques are associated with low strain values and can be distinguished from the surrounding soft material, which exhibits elevated strain. For the first time, circumferential intravascular OCE images are provided side by side with conventional OCT images, simultaneously mapping both the tissue structure and stiffness

Motorized capsule for shadow-free OCT imaging and synchronous beam control

We demonstrate a tethered motorized capsule for unobstructed Optical Coherence Tomography (OCT) imaging of the esophagus. By using a distal reflector design, we avoided the common shadow artifact induced by the motor wires. A synchronous driving technique features three types of beam scanning modes of the capsule i.e. circumferential beam scanning, localized beam scanning and accurate beam positioning. We characterized these three modes and carried out in vitro imaging experiments using the capsule. The results show that the capsule can potentially be a useful tool for diagnostic OCT imaging and OCT-guided biopsy and therapy of the esophagus

Heartbeat OCT: in vivo intravascular megahertz-optical coherence tomography

Cardiac motion artifacts, non-uniform rotational distortion and undersampling affect the image quality and the diagnostic impact of intravascular optical coherence tomography (IV-OCT). In this study we demonstrate how these limitations of IV-OCT can be addressed by using an imaging system that we called “Heartbeat OCT”, combining a fast Fourier Domain Mode Locked laser, fast pullback, and a micromotor actuated catheter, designed to examine a coronary vessel in less than one cardiac cycle. We acquired in vivo data sets of two coronary arteries in a porcine heart with both Heartbeat OCT, working at 2.88 MHz A-line rate, 4000 frames/s and 100 mm/s pullback speed, and with a commercial system. The in vivo results show that Heartbeat OCT provides faithfully rendered, motion-artifact free, fully sampled vessel wall architecture, unlike the conventional IV-OCT data. We present the Heartbeat OCT system in full technical detail and discuss the steps needed for clinical translation of the technology

MOESM1 of Disruption of a putative mitochondrial oxaloacetate shuttle protein in Aspergillus carbonarius results in secretion of malic acid at the expense of citric acid production

Additional file 1: Figure S1. Transcriptional analysis of the mtpA gene

Disruption of a putative mitochondrial oxaloacetate shuttle protein in Aspergillus carbonarius results in secretion of malic acid at the expense of citric acid production

Abstract Background In filamentous fungi, transport of organic acids across the mitochondrial membrane is facilitated by active transport via shuttle proteins. These transporters may transfer different organic acids across the membrane while taking others the opposite direction. In Aspergillus niger, accumulation of malate in the cytosol can trigger production of citric acid via the exchange of malate and citrate across the mitochondrial membrane. Several mitochondrial organic acid transporters were recently studied in A. niger showing their effects on organic acid production. Results In this work, we studied another citric acid producing fungus, Aspergillus carbonarius, and identified by genome-mining a putative mitochondrial transporter MtpA, which was not previously studied, that might be involved in production of citric acid. This gene named mtpA encoding a putative oxaloacetate transport protein was expressed constitutively in A. carbonarius based on transcription analysis. To study its role in organic acid production, we disrupted the gene and analyzed its effects on production of citric acid and other organic acids, such as malic acid. In total, 6 transformants with gene mtpA disrupted were obtained and they showed secretion of malic acid at the expense of citric acid production. Conclusion A putative oxaloacetate transporter gene which is potentially involved in organic acid production by A. carbonarius was identified and further investigated on its effects on production of citric acid and malic acid. The mtpA knockout strains obtained produced less citric acid and more malic acid than the wild type, in agreement with our original hypothesis. More extensive studies should be conducted in order to further reveal the mechanism of organic acid transport as mediated by the MtpA transporter