A veritable explosion of primary research papers within the past 10 years focuses on nucleolar and ribosomal stress, and for good reason: with ribosome biosynthesis consuming ~80% of a cell’s energy, nearly all metabolic and signaling pathways lead ultimately to or from the nucleolus. We begin by describing p53 activation upon nucleolar stress resulting in cell cycle arrest or apoptosis. The significance of this mechanism cannot be understated, as oncologists are now inducing nucleolar stress strategically in cancer cells as a potential anti-cancer therapy. We also summarize the human ribosomopathies, syndromes in which ribosome biogenesis or function are impaired leading to birth defects or bone narrow failures; the perplexing problem in the ribosomopathies is why only certain cells are affected despite the fact that the causative mutation is systemic. We then describe p53-independent nucleolar stress, first in yeast which lacks p53, and then in other model metazoans that lack MDM2, the critical E3 ubiquitin ligase that normally inactivates p53. Do these presumably ancient p53-independent nucleolar stress pathways remain latent in human cells? If they still exist, can we use them to target >50% of known human cancers that lack functional p53?

Mammalian nucleostemin (NS) is a nucleolar guanosine triphosphate-binding protein implicated in cell cycle progression, stem cell proliferation, and ribosome assembly. Drosophila melanogaster contains a four-member nucleostemin family (NS1-4). NS1 is the closest orthologue to human NS; it shares 33% identity and 67% similarity with human NS. We show that NS1 has intrinsic GTPase and ATPase activity and that it is present within nucleoli of most larval and adult cells. Endogenous NS1 and lightly expressed green fluorescent protein (GFP)-NS1 enrich within the nucleolar granular regions as expected, whereas overexpressed GFP-NS1 localized throughout the nucleolus and nucleoplasm, and to several transcriptionally active interbands of polytene chromosomes. Severe overexpression correlated with the appearance of melanotic tumors and larval/pupal lethality. Depletion of 60% of NS1 transcripts also lead to larval and pupal lethality. NS1 protein depletion correlated with the loss of imaginal island (precursor) cells in the larval midgut and to an apparent block in the nucleolar release of large ribosomal subunits in terminally differentiated larval midgut polyploid cells. Ultrastructural examination of larval Malpighian tubule cells depleted for NS1 showed a loss of cytoplasmic ribosomes and a concomitant appearance of cytoplasmic preautophagosomes and lysosomes. We interpret the appearance of these structures as indicators of cell stress response. INTRODUCTIONMammalian nucleostemin (NS) is a nucleolar guanosine triphosphate (GTP)-binding protein first characterized in embryonic and neuronal stem cells and in certain cancer cells where it probably plays regulatory roles in cell cycle progression and ribosome biogenesis McKay, 2002, 2005; reviewed by Ma and Pederson, 2008b). Steadystate concentrations of NS drop to undetectable levels just before rat cortical stem cell differentiation (Tsai and McKay, 2002), suggesting that reduced expression of NS regulates stem cell proliferation and differentiation by triggering exit from the cell cycle (Normile, 2002;Tsai and McKay, 2002;Beekman et al., 2006). Mammalian NS rapidly cycles between the nucleolus and the nucleoplasm. Retention of NS within the nucleolus is prolonged when it binds GTP (Misteli, 2005;Tsai and McKay, 2005;Meng et al., 2006Meng et al., , 2007. GTP bound to the central region of NS is thought to stabilize interactions between its amino-terminal basic domain and other nucleolar components, whereas NS redistributes to the nucleoplasm when GTP binding is impaired by mutation (Tsai and McKay, 2005). Coimmunoprecipitation, yeast twohybrid, and bimolecular fluorescence complementation assays demonstrated an interaction between NS and nucleophosmin (B23) (Ma and Pederson, 2008a), a multifunctional chaperone that probably participates in the later stages of ribosome assembly within the granular component of nucleoli. Similar to NS, nucleophosmin probably plays a role in cell proliferation (Szebeni et al., 2003;Grisendi et al., 2006). Recent studies suggest that NS ...

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Background: COVID-19, caused by SARS-CoV-2, is still a global public health concern due to the absence of effective antiviral treatment against different strains. Studies have shown that pregnant women are more susceptible to COVID-19 due to altered physiology and immunological features. Therefore, this study was designed to investigate pregnant women's knowledge, attitudes, and practice (KAP) to prevent COVID-19 and determine the factors associated with KAP. Methods: A community-based cross-sectional study was conducted among 425 pregnant women in Northern Bangladesh. The samples were obtained using a simple random sampling technique from April 5 to June 15, 2020. The data were collected by face-to-face survey with a structured and pre-tested questionnaire and analyzed using SPSS version 25. Bivariable and multivariable logistic regression analyses were performed, and p-values < 0.05 at 95% CI were considered statistically significant. Results: Overall, the score of KAP among the respondents was 47.76%, 49.41%, and 56.24%, respectively. Participants' area of residence, educational status of the husband, and antenatal care (ANC) visit were significantly associated with the level of knowledge, whereas age, educational status of the husband, number of living children, and knowledge were significant predictors of attitude. The knowledge of COVID-19 was the only predictor associated with the practice. Conclusion: Our study shows that almost half of the participants had poor knowledge, a negative attitude, and poor practices toward COVID-19. Additional health education programs by healthcare professionals and different media, coordinated and combined efforts of government and individuals' participation will be required to fight the spread of the infection.