Evaluation of a fully automated computed tomography image segmentation method for fast and accurate body composition measurements

Introduction: Body composition evaluation can be used to assess patients’ nutritional status to predict clinical outcomes. To facilitate reliable and time-efficient body composition measurements eligible for clinical practice, fully automated computed tomography segmentation methods were developed. The aim of this study was to evaluate automated segmentation by Data Analysis Facilitation Suite in an independent dataset.Materials and methods: Preoperative computed tomography images were used of 165 patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy from 2014 to 2019. Manual and automated measurements of skeletal muscle mass (SMM), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and intramuscular adipose tissue (IMAT) were performed at the third lumbar vertebra. Segmentation accuracy of automated measurements was assessed using the Jaccard index and intra-class correlation coefficients.Results: Automatic segmentation provided accurate measurements compared to manual analysis, resulting in Jaccard score coefficients of 94.9 for SMM, 98.4 for VAT, 99.1 for SAT, and 79.4 for IMAT. Intra-class correlation coefficients ranged from 0.98 to 1.00. Automated measurements on average overestimated SMM and SAT areas compared to manual analysis, with mean differences (±2 standard deviations) of 1.10 (–1.91 to 4.11) and 1.61 (–2.26 to 5.48) respectively. For VAT and IMAT, automated measurements on average underestimated the areas with mean differences of –1.24 (–3.35 to 0.87) and –0.93 (–5.20 to 3.35), respectively.Conclusions: Commercially available Data Analysis Facilitation Suite provides similar results compared to manual measurements of body composition at the level of third lumbar vertebra. This software provides accurate and time-efficient body composition measurements, which is necessary for implementation in clinical practice.</p

The DNA/RNA-Dependent RNA Polymerase QDE-1 Generates Aberrant RNA and dsRNA for RNAi in a Process Requiring Replication Protein A and a DNA Helicase

The Neurospora RNA-dependent RNA polymerase QDE-1 is an RNA polymerase that can use both RNA and DNA as templates, suggesting a new mechanism for small RNA production

The Werner Syndrome Helicase/Exonuclease Processes Mobile D-Loops through Branch Migration and Degradation

RecQ DNA helicases are critical for preserving genome integrity. Of the five RecQ family members identified in humans, only the Werner syndrome protein (WRN) possesses exonuclease activity. Loss of WRN causes the progeroid disorder Werner syndrome which is marked by cancer predisposition. Cellular evidence indicates that WRN disrupts potentially deleterious intermediates in homologous recombination (HR) that arise in genomic and telomeric regions during DNA replication and repair. Precisely how the WRN biochemical activities process these structures is unknown, especially since the DNA unwinding activity is poorly processive. We generated biologically relevant mobile D-loops which mimic the initial DNA strand invasion step in HR to investigate whether WRN biochemical activities can disrupt this joint molecule. We show that WRN helicase alone can promote branch migration through an 84 base pair duplex region to completely displace the invading strand from the D-loop. However, substrate processing is altered in the presence of the WRN exonuclease activity which degrades the invading strand both prior to and after release from the D-loop. Furthermore, telomeric D-loops are more refractory to disruption by WRN, which has implications for tighter regulation of D-loop processing at telomeres. Finally, we show that WRN can recognize and initiate branch migration from both the 5′ and 3′ ends of the invading strand in the D-loops. These findings led us to propose a novel model for WRN D-loop disruption. Our biochemical results offer an explanation for the cellular studies that indicate both WRN activities function in processing HR intermediates

G-Quadruplex DNA Sequences Are Evolutionarily Conserved and Associated with Distinct Genomic Features in Saccharomyces cerevisiae

G-quadruplex DNA is a four-stranded DNA structure formed by non-Watson-Crick base pairing between stacked sets of four guanines. Many possible functions have been proposed for this structure, but its in vivo role in the cell is still largely unresolved. We carried out a genome-wide survey of the evolutionary conservation of regions with the potential to form G-quadruplex DNA structures (G4 DNA motifs) across seven yeast species. We found that G4 DNA motifs were significantly more conserved than expected by chance, and the nucleotide-level conservation patterns suggested that the motif conservation was the result of the formation of G4 DNA structures. We characterized the association of conserved and non-conserved G4 DNA motifs in Saccharomyces cerevisiae with more than 40 known genome features and gene classes. Our comprehensive, integrated evolutionary and functional analysis confirmed the previously observed associations of G4 DNA motifs with promoter regions and the rDNA, and it identified several previously unrecognized associations of G4 DNA motifs with genomic features, such as mitotic and meiotic double-strand break sites (DSBs). Conserved G4 DNA motifs maintained strong associations with promoters and the rDNA, but not with DSBs. We also performed the first analysis of G4 DNA motifs in the mitochondria, and surprisingly found a tenfold higher concentration of the motifs in the AT-rich yeast mitochondrial DNA than in nuclear DNA. The evolutionary conservation of the G4 DNA motif and its association with specific genome features supports the hypothesis that G4 DNA has in vivo functions that are under evolutionary constraint

Transcription-replication conflicts: How they occur and how they are resolved

The frequent occurrence of transcription and DNA replication in cells results in many encounters, and thus conflicts, between the transcription and replication machineries. These conflicts constitute a major intrinsic source of genome instability, which is a hallmark of cancer cells. How the replication machinery progresses along a DNA molecule occupied by an RNA polymerase is an old question. Here we review recent data on the biological relevance of transcription-replication conflicts, and the factors and mechanisms that are involved in either preventing or resolving them, mainly in eukaryotes. On the basis of these data, we provide our current view of how transcription can generate obstacles to replication, including torsional stress and non-B DNA structures, and of the different cellular processes that have evolved to solve them

DETERMINATION OF PORESIZE AND PERMEABILITY BY INDUCED POLARIZATION TECHNIQUES IN CLAY SAMPLES OF COASTAL ANDHRA PRADESH

Using the similarity between poresize and IP relaxation time a cost effective method of determining permeability in coastal Andhra Pradesh has been worked out. The results have found greater matching in the medium grade</jats:p