Search Results (3)

Beyond its function as a carrier of hereditary information, recent research has uncovered novel properties of extracellular DNA, including its role in the adaptation to the environment when released from plants. The secreted DNA has been shown to exert insecticidal effects against insect pests, which play an adaptive role in plant-insect interactions, particularly in regulating populations of economically important sap-feeding insects. The molecular mechanisms underlying this insecticidal effect are underinvestigated and remain largely unknown. Therefore, there is a need for more efforts to uncover these mechanisms to better understand plant–pest interactions, which would provide new insights into natural pest control strategies and inspire biotechnological applications. In the current study, we show that Pittosporum tobira (P. tobira) secretes single-stranded DNA (ssDNA) that exerts an insecticidal effect on Coccus hesperidum (C. hesperidum). We collected extracellular DNA from P. tobira leaves and tested its potential insecticidal effect by applying it to C. hesperidum, which is a well-known pest that causes damage to P. tobira. Our results revealed that the outermost layer of the leaf cuticle of P. tobira predominantly contains ssDNA of approximately 100 nt in length, originating from both chloroplast and nuclear genomes. This DNA exhibited pronounced insecticidal activity against C. hesperidum, with chloroplast-derived sequences significantly enriched compared to the total DNA in intact plant cells. These findings suggest that the microevolution of the P. tobira nucleome and plastome contributed to the formation of extracellular DNA with insecticidal properties (eci-DNA), which is part of its defense strategy against insect pests. Moreover, in this article, for the first time, we show that antisense DNA (illustrated with oligonucleotide insecticide Coccus-11) is capable of activating insect retrotransposons and upregulating their RT-RNase H, a crucial enzyme for the DNA containment mechanism and successful action of oligonucleotide insecticides. Notably, the laboratory-developed ssDNA-based ‘genetic zipper’ technology, designed for sustainable pest management, possesses characteristics similar to eci-DNA found in nature, highlighting a potential natural parallel to this biotechnological approach for sustainable pest management. Full article

Background: Prostate cancer (PCa) has a high lifetime prevalence (one out of six men), but currently there is no widely accepted screening programme. Widely used prostate specific antigen (PSA) test at cut-off of 3.0 ng/mL does not have sufficient accuracy for detection of any prostate cancer, resulting in numerous unnecessary prostate biopsies in men with benign disease and false reassurance in some men with PCa. We have recently identified circulating chromosome conformation signatures (CCSs, Episwitch^® PCa test) allowing PCa detection and risk stratification in line with standards of clinical PCa staging. The purpose of this study was to determine whether combining the Episwitch PCa test with the PSA test will increase its diagnostic accuracy. Methods: n = 109 whole blood samples of men enrolled in the PROSTAGRAM screening pilot study and n = 38 samples of patients with established PCa diagnosis and cancer-negative controls from Imperial College NHS Trust were used. Samples were tested for PSA, and the presence of CCSs in the loci encoding for of DAPK1, HSD3B2, SRD5A3, MMP1, and miRNA98 associated with high-risk PCa identified in our previous work. Results: PSA > 3 ng/mL alone showed a low positive predicted value (PPV) of 0.14 and a high negative predicted value (NPV) of 0.93. EpiSwitch alone showed a PPV of 0.91 and a NPV of 0.32. Combining PSA and Episwitch tests has significantly increased the PPV to 0.81 although reducing the NPV to 0.78. Furthermore, integrating PSA, as a continuous variable (rather than a dichotomised 3 ng/mL cut-off), with EpiSwitch in a new multivariant stratification model, Prostate Screening EpiSwitch (PSE) test, has yielded a remarkable combined PPV of 0.93 and NPV of 0.95 when tested on the independent combined cohort. Conclusions: Our results demonstrate that combining the standard PSA readout with circulating chromosome conformations (PSE test) allows for significantly enhanced PSA PPV and overall accuracy for PCa detection. The PSE test is accurate, rapid, minimally invasive, and inexpensive, suggesting significant screening diagnostic potential to minimise unnecessary referrals for expensive and invasive MRI and/or biopsy testing. Further extended prospective blinded validation of the new combined signature in a screening cohort with low cancer prevalence would be the recommended step for PSE adoption in PCa screening. Full article

Non-random spatial organization of the chromosomal material inside the nuclei of brain cells emerges as an important regulatory layer of genome organization and function in health and disease. Here, we discuss how integrative approaches assessing chromatin in context of the 3D genome is providing new insights into normal and diseased neurodevelopment. Studies in primate (incl. human) and rodent brain have confirmed that chromosomal organization in neurons and glia undergoes highly dynamic changes during pre- and early postnatal development, with potential for plasticity across a much wider age window. For example, neuronal 3D genomes from juvenile and adult cerebral cortex and hippocampus undergo chromosomal conformation changes at hundreds of loci in the context of learning and environmental enrichment, viral infection, and neuroinflammation. Furthermore, locus-specific structural DNA variations, such as micro-deletions, duplications, repeat expansions, and retroelement insertions carry the potential to disrupt the broader epigenomic and transcriptional landscape far beyond the boundaries of the site-specific variation, highlighting the critical importance of long-range intra- and inter-chromosomal contacts for neuronal and glial function. Full article