Radiotherapy is not currently informed by the genetic composition of an individual patient's tumour. To identify genetic features regulating survival after DNA damage, here we conduct large-scale profiling of cellular survival after exposure to radiation in a diverse collection of 533 genetically annotated human tumour cell lines. We show that sensitivity to radiation is characterized by significant variation across and within lineages. We combine results from our platform with genomic features to identify parameters that predict radiation sensitivity. We identify somatic copy number alterations, gene mutations and the basal expression of individual genes and gene sets that correlate with the radiation survival, revealing new insights into the genetic basis of tumour cellular response to DNA damage. These results demonstrate the diversity of tumour cellular response to ionizing radiation and establish multiple lines of evidence that new genetic features regulating cellular response after DNA damage can be identified.

The adsorption of amyloidogenic peptides, amyloid beta 1–40 (Aβ1–40), alpha-synuclein (α-syn), and beta 2 microglobulin (β2m), was attempted over the surface of nano-gold colloidal particles, ranging from d = 10 to 100 nm in diameter (d). The spectroscopic inspection between pH 2 and pH 12 successfully extracted the critical pH point (pHo) at which the color change of the amyloidogenic peptide-coated nano-gold colloids occurred due to aggregation of the nano-gold colloids. The change in surface property caused by the degree of peptide coverage was hypothesized to reflect the ΔpHo, which is the difference in pHo between bare gold colloids and peptide coated gold colloids. The coverage ratio (Θ) for all amyloidogenic peptides over gold colloid of different sizes was extracted by assuming Θ = 0 at ΔpHo = 0. Remarkably, Θ was found to have a nano-gold colloidal size dependence, however, this nano-size dependence was not simply correlated with d. The geometric analysis and simulation of reproducing Θ was conducted by assuming a prolate shape of all amyloidogenic peptides. The simulation concluded that a spiking-out orientation of a prolate was required in order to reproduce the extracted Θ. The involvement of a secondary layer was suggested; this secondary layer was considered to be due to the networking of the peptides. An extracted average distance of networking between adjacent gold colloids supports the binding of peptides as if they are “entangled” and enclosed in an interfacial distance that was found to be approximately 2 nm. The complex nano-size dependence of Θ was explained by available spacing between adjacent prolates. When the secondary layer was formed, Aβ1–40 and α-syn possessed a higher affinity to a partially negative nano-gold colloidal surface. However, β2m peptides tend to interact with each other. This difference was explained by the difference in partial charge distribution over a monomer. Both Aβ1–40 and α-syn are considered to have a partial charge (especially δ+) distribution centering around the prolate axis. The β2m, however, possesses a distorted charge distribution. For a lower Θ (i.e., Θ <0.5), a prolate was assumed to conduct a gyration motion, maintaining the spiking-out orientation to fill in the unoccupied space with a tilting angle ranging between 5° and 58° depending on the nano-scale and peptide coated to the gold colloid.

Background: Uncontrolled neuroinflammation and microglia activation lead to cellular and tissue damage contributing to neurodegenerative and neurological disorders. Spirulina (Arthrospira platensis (Nordstedt) Gomont, or Spirulina platensis), a blue-green microalga, which belongs to the class of cyanobacteria, has been studied for its numerous health benefits, which include anti-inflammatory properties, among others. Furthermore, in vivo studies have highlighted neuroprotective effects of Spirulina from neuroinflammatory insults in different brain areas. However, the mechanisms underlying the anti-inflammatory effect of the microalga are not completely understood. In this study we examined the effect of pre- and post-treatment with an acetone extract of Spirulina (E1) in an in vitro model of LPS-induced microglia activation.Methods: The effect of E1 on the release of IL-1β and TNF-α, expression of iNOS, nuclear factor erythroid 2–related factor 2 (Nrf2), and heme oxygenase-1 (HO-1), and the activation of NF-κB was investigated in primary microglia by ELISA, real-time PCR, and immunofluorescence.Results: Pre- and early post-treatment with non-cytotoxic concentrations of E1 down-regulated the release of IL-1β and TNF-α, and the over-expression of iNOS induced by LPS. E1 also significantly blocked the LPS-induced nuclear translocation of NF-κB p65 subunit, and upregulated gene and protein levels of Nrf2, as well as gene expression of HO-1.Conclusions: These results indicate that the extract of Spirulina can be useful in the control of microglia activation and neuroinflammatory processes. This evidence can support future in vivo studies to test pre- and post-treatment effects of the acetone extract from Spirulina.

The advent of massively parallel sequencing (MPS) in the past decade has opened the doors to mitochondrial whole-genome sequencing. Mitochondrial (mt) DNA is used in forensics due to its high copy number per cell and maternal mode of inheritance. Consequently, we have implemented the Thermo Fisher Precision ID mtDNA Whole Genome panel coupled with the Ion Chef™ and Ion S5™ for MPS analysis in the California Department of Justice, Missing Persons DNA Program. Thirty-one mostly challenging samples (degraded, inhibited, low template, or mixed) were evaluated for this study. The majority of these samples generated single source full or partial genome sequences with MPS, providing information in cases where previously there was none. The quantitative and sensitive nature of MPS analysis was beneficial, but also led to detection of low-level contaminants. In addition, we found Precision ID to be more susceptible to inhibition than our legacy Sanger assay. Overall, the success rate (full single source hypervariable regions I and II (HVI/HVII) for Sanger and control region for MPS result) for these challenging samples increased from 32.3% with Sanger sequencing to 74.2% with the Precision ID assay. Considering the increase in success rate, the simple workflow and the higher discriminating potential of whole genome data, the Precision ID platform is a significant improvement for the CA Department of Justice Missing Persons DNA Program.

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