The effect of the nucleus random location on the cellular S-values - Based on Geant4-DNA.

INTRODUCTION: The nucleus is the most crucial target in cell micro-dosimetry. At cell division time, cells do not have concentric geometry synchronously. This issue will be more essential for the low-energy electron emitters. This study investigates the variety of mean absorbed dose (S-value) in the non-concentric cell-nucleus model and random nucleus location within the cell. METHODS: The S-values were calculated by Geant4-DNA for the cell and nucleus with different radius (with the RC/RN ratio = 1.2, 2, 3) and the cell geometry contains nuclei with varying positions inside the cell. Two important components, cytoplasm to the nucleus (N←Cy) and the cell surface to the nucleus (N←Cs) are considered in this work for mono energetic electrons (10-100 keV). To eliminate the effect of the nucleus position (during cell division) on the S-value, the nucleus location in each run was randomly selected inside the cell to represent the cell in a floating state. RESULTS: As the nucleus becomes closer to the cell membrane the differences are more noticeable especially for electrons with energy less than 20 keV as for RN/RC = 1.2, 2, and 3 about 18, 70, and 200%, respectively. CONCLUSION: Due to the variable position of the nucleus in cell division, using a random place defined in Geant4, the calculations are getting closer to the reality while there is not such possibility for analytical method used by MIRD.

Scoping review of chronic rhinosinusitis proteomics.

BACKGROUND: Progressive advances in proteomic technology has improved our understanding of the chronic rhinosinusitis (CRS) pathogenesis and endotypes. This scoping review aims to present a comprehensive and descriptive analysis of nasal mucosa and mucus proteome of CRS patients. METHODOLOGY: Studies investigating the proteome of nasal mucosa and mucus from healthy and CRS patients via mass spectrometry were included. Critical appraisal of methodological quality was conducted with extraction of protein lists. Gene set enrichment analysis (GSEA) was performed on studies including CRS patients. RESULTS: 2962 proteins were identified in the 21 studies included in this review. Eleven studies investigated the nasal mucus proteome and ten studies investigated the nasal mucosa proteome. Studies demonstrated heterogeneity in patients, sampling and mass spectrometry methodology. Samples from CRS patients suggested a trend in enrichment of immune system and programmed cell death pathways. Increased expression of proteins involved in cellular components including the cytoskeleton and adherens junctions was also present in CRS. CONCLUSIONS: Alterations in the healthy sinonasal proteome may lead to the increased immunological, metabolic and tissue remodeling processes observed in CRS. However, it is difficult to draw significant conclusions from the GSEA due to the heterogeneity present in the limited literature available. These findings allow us to direct further research to better understand CRS pathogenesis and its endotypes.

Optimization of Brain Tumor MR Image Classification Accuracy Using Optimal Threshold, PCA and Training ANFIS with Different Repetitions.

BACKGROUND: One of the leading causes of death is brain tumors. Accurate tumor classification leads to appropriate decision making and providing the most efficient treatment to the patients. This study aims to optimize brain tumor MR images classification accuracy using optimal threshold, PCA and training Adaptive Neuro Fuzzy Inference System (ANFIS) with different repetitions. MATERIAL AND METHODS: The procedure used in this study consists of five steps: (1) T1, T2 weighted images collection, (2) tumor separation with different threshold levels, (3) feature extraction, (4) presence and absence of feature reduction applying principal component analysis (PCA) and (5) ANFIS classification with 0, 20 and 200 training repetitions. RESULTS: ANFIS accuracy was 40%, 80% and 97% for all features and 97%, 98.5% and 100% for the 6 selected features by PCA in 0, 20 and 200 training repetitions, respectively. CONCLUSION: The findings of the present study demonstrated that accuracy can be raised up to 100% by using an optimized threshold method, PCA and increasing training repetitions.

Purification of α-synuclein containing inclusions from human post mortem brain tissue.

UNLABELLED: Comparison with existing methods. BACKGROUND: Neurodegenerative disorders affect a large proportion of the elderly population. A group of disorders, known as the α-synucleinopathies, are characterised by the presence of α-synuclein-containing protein inclusions, such as Lewy Bodies (LBs) found in neurons from Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB), and Glial Cytoplasmic Inclusions (GCIs) found in oligodendrocytes from Multiple System Atrophy (MSA). The analysis of the protein composition of inclusions has been hindered by limitations of methods for isolating the inclusions from the surrounding tissue. METHOD: Four modifications were made to the published method for GCI purification by Gai et al. (1999) which were: collecting the entire inclusion-containing part of the Percoll gradient; lysis of nuclei prior to DNAse digestion; limited tryptic digestion to release inclusions from the cytoskeletal meshwork; and increased antibody and magnetic bead concentrations/volumes to capture the larger amounts of inclusions. RESULTS: The optimised method gave a 28-fold increase in yield compared to the published method of Gai et al. (1999). A 2D-DIGE comparison revealed a 3.8-fold increase in α-synuclein enrichment and a corresponding 5.2-fold reduction in tubulin contamination. This method was also successfully adapted to the purification of LBs from DLB tissue. A 2D-DIGE comparison of purified GCIs (n=2) revealed that GCIs consist of 11.7% α-synuclein, 1.9% α-ß-crystallin and 2.3% 14-3-3 proteins compared to 8.5%, 2.0% and 1.5% in LBs, respectively. CONCLUSIONS: This study has generated an improved method for the purification of α-synuclein-containing inclusions with a yield sufficient for multiple forms of analysis.

Extended boiling of peanut progressively reduces IgE allergenicity while retaining T cell reactivity.

BACKGROUND: Current peanut oral immunotherapy is hampered by frequent adverse events. It has been shown that boiling can reduce peanut allergenicity. Hypoallergenic peanut products have the potential to reduce treatment-related reactions during desensitization. OBJECTIVE: To show that extended boiling (for up to 12 h) can progressively reduce peanut allergenicity while retaining T cell reactivity. METHODS: Raw peanuts were boiled for half, 1, 2, 4 and 12 h in deionized water. After dehydration, boiled and raw peanuts were ground, defatted and soluble proteins extracted in PBS and cooking water (leachate) retained. SDS-PAGE, Western blot, inhibition ELISA, mass spectrometry and skin prick test were used to characterize changes to peanut allergens and human IgE reactivity. T cell responses to raw and boiled peanut extracts were determined by proliferation of CD4+/CD25+/CD134+ T cells in peanut-allergic and non-allergic individuals. RESULTS: Extended boiling progressively reduced peanut allergenicity through a combination of leaching of allergens into cooking water, fragmentation of allergens and denaturation of conformational epitopes. Two-hour boiling led to an eightfold reduction in IgE binding capacity of boiled peanuts as determined by inhibition ELISA, while 12-h boiling led to a 19-fold reduction. Mass spectrometry revealed an increasing number of unique allergen peptides with longer boiling times. Raw, 2- and 12-h boiled peanut extracts were equivalent in their ability to stimulate T cell activation and proliferation. CONCLUSION AND CLINICAL RELEVANCE: Progressive reduction in peanut allergenicity with extended boiling does not affect T cell reactivity. Boiled peanuts may be a candidate for oral immunotherapy.