Summary
Faithful chromosome segregation in meiosis requires crossover (CO) recombination, which is regulated to ensure at least one CO per homolog pair. We investigate failure to ensure COs in juvenile male mice. By monitoring recombination genome-wide using cytological assays and at hotspots using molecular assays, we show that juvenile mouse spermatocytes have fewer COs relative to adults. Analysis of recombination in the absence of MLH3 provides evidence for greater utilization in juveniles of pathways involving structure-selective nucleases and/or alternative complexes, which can act upon precursors to generate noncrossovers (NCOs) at the expense of COs. We propose that some designated CO sites fail to mature efficiently in juveniles owing to inappropriate activity of these alternative repair pathways, leading to chromosome mis-segregation. We also find lower MutLγ focus density in juvenile human spermatocytes, suggesting that weaker CO maturation efficiency may explain why younger men have higher risk of fathering children with Down syndrome.
Cisplatin occupies a crucial role in the treatment of various malignant tumours. However, its efficacy and applicability are heavily restricted by severe systemic toxicities and drug resistance. Our study exploits the active targeting of supramolecular metallacages to enhance the activity of cisplatin in cancer cells while reducing its toxicity. Thus, Pd2L4 cages (L = ligand) have been conjugated to four integrin ligands with different binding affinity and selectivity. Cage formation and encapsulation of cisplatin was proven by NMR spectroscopy. Upon encapsulation, cisplatin showed increased cytotoxicity in vitro, in melanoma A375 cells overexpressing αvβ3 integrins. Moreover, ex vivo studies in tissue slices indicated reduced toxicity towards healthy liver and kidney tissues for cage-encapsulated cisplatin. Analysis of metal content by ICP-MS demonstrated that encapsulated drug is less accumulated in these organs compared to the 'free' one.
Combining plasma activation and cross-reactivity of sensor array, we have developed a plasma-assisted cataluminescence (PA-CTL) sensor array for fast sensing and discrimination of gaseous hydrocarbons, which can be potentially used for fast diagnosis of lung cancer. Based on dielectric barrier discharge, a low-temperature plasma is generated to activate gaseous hydrocarbons with low cataluminescence (CTL) activities. Extremely increased CTL responses have been obtained, which resulted in a plasma assistance factor of infinity (∞) for some hydrocarbons. On a 4 × 3 PA-CTL sensor array made from alkaline-earth nanomaterials, gaseous hydrocarbons showed robust and unique CTL responses to generate characteristic patterns for fast discrimination. Because of the difference in the component of hydrocarbons in breath, exhaled breath samples from donors with and without lung cancer were tested, and good discrimination has been achieved by this technique. In addition, the feasibility of multidimentional detection based on temperature was confirmed. It had good reproducibility and gave a linear range of 65-6500 ng/mL or 77-7700 ppmv (R > 0.98) for CH(4) with a detection limit of 33 ng/mL (38 ppmv) on MgO. The PA-CTL sensor array is simple, low-cost, thermally stable, nontoxic, and has an abundance of alkaline-earth nanomaterials to act as sensing elements. This has expanded the applications of CTL-based senor arrays and will show great potential in clinical fast diagnosis.
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