Domain-specific Quantification of Prion Protein in Cerebrospinal Fluid by Targeted Mass Spectrometry

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Highlights

• •Targeted mass spectrometry assay to quantify prion protein (PrP) in spinal fluid.
• •Precise measurement of PrP peptide concentration across protein domains.
• •Peptides are uniformly decreased in symptomatic prion disease patients.
• •Assay applicable to humans and preclinical species for drug development.

     

Changes in Synaptic Proteins Precede Neurodegeneration Markers in Preclinical Alzheimer's Disease Cerebrospinal Fluid

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Highlights

• •Proteomic analysis of cerebrospinal fluid and identification of synaptic component.
• •Use of super resolution microscopy to verify synapse-specificity in human tissue.
• •Selective reaction monitoring MS (SRM) of synaptic panel in 3 cohorts of Alzheimer's disease cerebrospinal fluid.
• •Synaptic protein changes precede tau in preclinical Alzheimer's disease.

     

Validated numerical fluid simulation of a thin‐layer cascade photobioreactor in OpenFOAM

Recently, microalgae have been considered as a promising alternative for the production of biofuels from CO₂. For the efficient cultivation of these microalgae, several types of photobioreactors have been designed and Pilot scale photobioreactors have been used to assess the performance of these reactors. Therein the primarily investigated reactor type is the Raceway Pond. However, the less researched Thin‐Layer Cascade Photobioreactor (TLC) shows a high potential for efficient production processes. Unfortunately, for low‐value products like biofuels costs must be kept to a minimum for an economic operation. To facilitate this, 3D Computational Fluid Dynamic simulations can be employed to estimate performance of reactor variants e.g. with respect to power input and mixing. Since up to now little effort has been put into the modelling of TLC reactors, this report aims to present a simulation approach for these reactors types that allows simple adaptation to different geometric or operational boundary conditions. All models have been generated for a two‐phase mixture in OpenFOAM. To demonstrate its applicability, validation measurements with a physical unit have been performed and were compared to the simulation results. With errors in the order of 10 % a successful simulation of the reactor geometry could be proven.     

Identification of Rabbit Oviductal Fluid Proteins Involved in Pre‐Fertilization Processes by Quantitative Proteomics

Oviductal fluid (ODF) proteins modulate and support reproductive processes in the oviduct. In the present study, proteins involved in the biological events that precede fertilization have been identified in the rabbit ODF proteome, isolated from the ampulla and isthmus of the oviduct at different time points within 8 h after intrauterine insemination. A workflow is used that integrates lectin affinity capture with stable‐isotope dimethyl labeling prior to nanoLC‐MS/MS analysis. In total, over 400 ODF proteins, including 214 lectin enriched glycoproteins, are identified and quantified. Selected data are validated by Western blot analysis. Spatiotemporal alterations in the abundance of ODF proteins in response to insemination are detected by global analysis. A subset of 63 potentially biologically relevant ODF proteins is identified, including extracellular matrix components, chaperones, oxidoreductases, and immunity proteins. Functional enrichment analysis reveals an altered peptidase regulator activity upon insemination. In addition to protein identification and abundance changes, N‐glycopeptide analysis further identifies 281 glycosites on 199 proteins. Taken together, these results show, for the first time, the evolving oviductal milieu early upon insemination. The identified proteins are likely those that modulate in vitro processes, including spermatozoa function.     

Potential roles and targeted therapy of the CXCLs/CXCR2 axis in cancer and inflammatory diseases

The chemokine receptor CXCR2 and its ligands are implicated in the progression of tumours and various inflammatory diseases. Activation of the CXCLs/CXCR2 axis activates multiple signalling pathways, including the PI3K, p38/ERK, and JAK pathways, and regulates cell survival and migration. The CXCLs/CXCR2 axis plays a vital role in the tumour microenvironment and in recruiting neutrophils to inflammatory sites. Extensive infiltration of neutrophils during chronic inflammation is one of the most important pathogenic factors in various inflammatory diseases. Chronic inflammation is considered to be closely correlated with initiation of cancer. In addition, immunosuppressive effects of myeloid-derived suppressor cells (MDSCs) against T cells attenuate the anti-tumour effects of T cells and promote tumour invasion and metastasis. Over the last several decades, many therapeutic strategies targeting CXCR2 have shown promising results and entered clinical trials. In this review, we focus on the features and functions of the CXCLs/CXCR2 axis and highlight its role in cancer and inflammatory diseases. We also discuss its potential use in targeted therapies.     

Microbial translocation into amniotic fluid of vervet monkeys is common and unrelated to adverse infant outcomes

Amniotic fluid was collected from pregnant female African green monkeys (n = 20). Analyses indicate microbial translocation into amniotic fluid during pregnancy is typical, and microbial load reduces across gestation. Microbial translocation does not relate to infant outcome or maternal factors. Lastly, we demonstrate that sample contamination is easily introduced and detectable.     

Magnetic resonance imaging based modeling of microvascular perfusion in patients with peripheral artery disease

Peripheral artery disease (PAD) is associated with an increased risk of adverse cardiovascular events, impaired lower extremity blood flow and microvascular perfusion abnormalities in the calf muscles which can be determined with contrast-enhanced magnetic resonance imaging (CE-MRI). We developed a computational model of the microvascular perfusion in the calf muscles. We included 20 patients (10 PAD, 10 controls) and utilized the geometry, mean signal intensity and arterial input functions from CE-MRI calf muscle perfusion scans. The model included the microvascular pressure (p_v), outflow filtration coefficient (OFC), transfer rate constant (k^t), porosity (φ), and the interstitial permeability (K_tissue). Parameters were fitted and the simulations were compared across PAD patients and controls. Intra-observer reproducibility of the simulated mean signal intensities was excellent (intraclass correlation coefficients >0.995). k^t and K_tissue were higher in PAD patients compared with controls (4.72 interquartile range (IQR) 3.33, 5.56 vs. 2.47 IQR 2.10, 2.85; p = 0.003; and 3.68 IQR 3.18, 4.41 vs. 1.81 IQR 1.81, 1.81; p < 0.001). Conversely, porosity (φ) was lower in PAD patients compared with controls (0.52 IQR 0.49, 0.54 vs. 0.61 IQR 0.58, 0.64; p = 0.016). Porosity (φ) was correlated with the ankle brachial index (r = 0.64, p = 0.011). The proposed computational microvascular model is robust and reproducible, and essential model parameters differ significantly between PAD patients and controls.