ABSTRACT
Centrosome amplification is a hallmark of cancer and PLK4 is one of the responsible factors for cancer associated centrosome amplification. Increased PLK4 levels was also shown to contribute to generation of cells with centriole amplification in mammalian tissues as olfactory neuron progenitor cells. PLK4 overexpression generates centriole rosette (CR) structures which harbor more than two centrioles each. Long term PLK4 overexpression results with centrosome amplification, but the maturation of amplified centrioles in CRs and linking of PLK4 induced amplified centrosomes has not yet been investigated in detail. Here, we show evidence for generation of large clustered centrosomes which have more than 2 centriole rosettes and define these structures as centriole rosette clusters (CRCs) in cells that have high PLK4 levels for 2 consecutive cell cycles. In addition, we show that PLK4 induced CRs follow normal centrosomal maturation processes and generate CRC structures that are inter-connected with canonical centrosomal linker proteins as C-Nap1, Rootletin and Cep68 in the second cell cycle after PLK4 induction. Increased PLK4 levels in cells with C-Nap1 and Rootletin knock-out resulted with distanced CRs and CRCs in interphase, while Nek2 knock-out inhibited separation of CRCs in prometaphase, providing functional evidence for the binding of CRC structures with centrosomal linker proteins. Taken together, these results suggest a cell cycle dependent model for PLK4 induced centrosome amplification which occurs in 2 consecutive cell cycles: (i) CR state in the first cell cycle, and (ii) CRC state in the second cell cycle.
Subject(s)
Centrioles , Neoplasms , Animals , Humans , Centrioles/metabolism , Centrosomal Associated Proteins , Cell Cycle Proteins/metabolism , Centrosome/metabolism , Neoplasms/metabolism , Mammals/metabolism , Protein Serine-Threonine Kinases/metabolismABSTRACT
BACKGROUND: This study aims to investigate the factors shaping resilience during the COVID-19 pandemic among people living with HIV (PLWH). METHODS: A total of 341 participants were included in this cross-sectional study. The online survey included scales of resilience, depression & anxiety, loneliness, social support, COVID-19 fear, stress, and sociodemographic information. RESULTS: Logistic regression test results showed loneliness (OR = 2.548, 95% CI = 1.251, 5.189), social support (OR = 2.217, 95% CI = 1.148, 4.279), income (OR = 2.581, 95% CI = 1.217, 5.472), sexual orientation (OR = 2.707, 95% CI = 1.004, 7.300), age (OR = 1.044, 95% CI = 1.006, 1.083) and COVID-19 fear (OR = 0.891, 95% CI = 0.840, 0.944) were statistically significant factors associated with resilience among PLWH. CONCLUSION: In conclusion, reducing COVID-19 fear by providing the correct information about the COVID-19 pandemic, fortifying the level of social support satisfaction, as well as minimising the level of loneliness have the potential to improve psychological resilience among PLWH.