👤 Marie-Renée Blanchet

Atherosclerosis is a chronic immunometabolic disease driven by lipid accumulation and immune cell infiltration. Macrophages and T cells play key roles throughout plaque development. Galectin-1 (Gal-1), a glycan-binding protein, modulates immune functions in these cells and has been reported to attenuate atherosclerosis, though its mechanisms remain incompletely understood. Here, we investigated the effects of Gal-1 on macrophages and T cells during plaque formation. Effects of Gal-1 on atherosclerosis, macrophages and T cells during lesion formation were studied in Apoe Gal-1 treatment reduced lesion size and increased circulating IL-10 levels, inversely correlating with plaque burden. Unexpectedly, IL-10 neutralization also mitigated atherosclerosis, indicating that its action is at least partially IL-10-independent. In plaques, Gal-1 promoted anti-inflammatory macrophage phenotypes, mirrored by a quiescent metabolic and anti-inflammatory profile in foamy macrophages ex vivo. The use of the Gal-1 Gal-1 protects against atherosclerosis associated with reprogramming macrophages and tuning T cell immunity through glycan-dependent and -independent pathways. Show less

Zinc-finger protein 768 (ZNF768) is an emerging transcription factor regulating cell proliferation and senescence. Although the role of ZNF768 in regulating cell fate decision has been demonstrated in vitro, its importance in controlling physiological and pathophysiological processes in vivo is still unclear. Here, we report the generation of a transgenic mouse model allowing the conditional overexpression of ZNF768. This was achieved by inserting an inverted Znf768 coding sequence surrounded by heterologous Cre recognition sites in the Gt(ROSA)26Sor mouse locus (FLExZnf768). To study the impact linked to systemic overexpression of ZNF768, mice carrying the FLExZnf768 allele were crossed with CMV-Cre mice to produce a whole-body ZNF768 transgenic mouse (WB-ZNF768-Tg). As expected, WB-ZNF768-Tg mice showed higher ZNF768 levels in various tissues. These mice were born at the expected Mendelian ratio and did not display apparent phenotypes. Because ZNF768 levels are often overexpressed in cancer, we assessed tumor development in WB-ZNF768-Tg mice. However, ZNF768 overexpression was not sufficient to promote 3-methylcholantrene-induced fibrosarcoma and KRAS Show less

Cell proliferation is a fundamental process required for organismal development, growth, and maintenance. Failure to control this process leads to several diseases, including cancer. Zinc finger protein 768 (ZNF768) is an emerging transcription factor that plays key roles in driving proliferation. In addition to controlling a gene network supporting cell division, ZNF768 physically interacts and inhibits the activity of the tumor suppressor p53. Although the importance of ZNF768 in promoting cell proliferation has been well demonstrated in vitro, the physiological and pathological roles of ZNF768 in vivo are still unknown. Here, we report the generation and characterization of a ZNF768 null mouse model. ZNF768 null mice are viable but show a growth defect early in life. Mouse embryonic fibroblasts (MEFs) isolated from ZNF768 null embryos exhibit higher p53 levels, premature senescence, and higher sensitivity to genotoxic stress. In line with these findings, ZNF768 null mice showed increased radiosensitivity. This effect was associated not only with higher expression of a subset of p53 target genes, but also with alterations in genes regulating transmembrane receptor signaling, cell adhesion, and growth. Because ZNF768 levels are elevated in tumors, we tested the impact of ZNF768 loss on cancer development in mice. Here, we show that ZNF768 deletion was sufficient to repress lung tumor development in a KRAS Show less

We report the first time-resolved study of the photochemistry of chlorine azide (ClN3) by femtosecond velocity-map imaging (fs-VMI). The dissociation dynamics are initiated at 4.6 eV and the photofragments are detected by multiphoton ionization using an intense laser field centered at 803 nm. A dissociation time of 262 ± 38 fs was measured from the rising time of the co-fragments N3 and Cl. The time dependency of the angular distribution of N3, which converges from β2 ~ 2 to β2 = 1.61 ± 0.07 in 170 ± 45 fs, reveals the parallel nature of the transition dipole moment. Show less