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Genome organization can regulate gene expression and promote cell fate transitions. The differentiation of germline stem cells (GSCs) to oocytes in Drosophila involves changes in genome organization mediated by heterochromatin and the nuclear pore complex (NPC). Heterochromatin represses germ cell genes during differentiation, and NPCs anchor these silenced genes to the nuclear periphery, maintaining silencing to allow for oocyte development. Surprisingly, we found that genome organization also contributes to NPC formation, mediated by the transcription factor Stonewall (Stwl). As GSCs differentiate, Stwl accumulates at boundaries between silenced and active gene compartments. Stwl at these boundaries plays a pivotal role in transitioning germ cell genes into a silenced state and activating a group of oocyte genes and nucleoporins (Nups). The upregulation of these Nups during differentiation is crucial for NPC formation and further genome organization. Thus, cross-talk between genome architecture and NPCs is essential for successful cell fate transitions., (© 2024 Kotb et al.; Published by Cold Spring Harbor Laboratory Press.)

The association of genomic loci to the nuclear periphery is proposed to facilitate cell type-specific gene repression and influence cell fate decisions. However, the interplay between gene position and expression remains incompletely understood, in part because the proteins that position genomic loci at the nuclear periphery remain unidentified. Here, we used an Oligopaint-based HiDRO screen targeting ∼1000 genes to discover novel regulators of nuclear architecture in Drosophila cells. We identified the heterochromatin-associated protein Stonewall (Stwl) as a factor promoting perinuclear chromatin positioning. In female germline stem cells (GSCs), Stwl binds and positions chromatin loci, including GSC differentiation genes, at the nuclear periphery. Strikingly, Stwl-dependent perinuclear positioning is associated with transcriptional repression, highlighting a likely mechanism for Stwl's known role in GSC maintenance and ovary homeostasis. Thus, our study identifies perinuclear anchors in Drosophila and demonstrates the importance of gene repression at the nuclear periphery for cell fate., (© 2024 Chavan et al.; Published by Cold Spring Harbor Laboratory Press.)

Layered double hydroxides have recently gained wide interest as promising multifunctional nanomaterials. In this work, a multifunctional ternary Zn-Co-Fe LDH was prepared and characterized using XRD, FTIR, BET, TEM, SEM, and EDX. This LDH showed a typical XRD pattern with a crystallite size of 3.52 nm and a BET surface area of 155.9 m 2 /g. This LDH was investigated, for the first time, as an adsorbent for moxifloxacin, a common fluoroquinolones antibiotic, showing a maximum removal efficiency and equilibrium time of 217.81 mg/g and 60 min, respectively. Its antifungal activity, for the first time, was investigated against Penicillium notatum, Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Mucor fungi at various concentrations (1000-1.95 µg/mL). This LDH was found to be effective against a variety of fungal strains, particularly Penicillium and Mucor species and showed zones of inhibition of 19.3 and 21.6 mm for Penicillium and Mucor, respectively, with an inhibition of 85% for Penicillium species and 68.3% for Mucormycosis. The highest antifungal efficacy results were obtained at very low MIC concentrations (33.3 and 62 µg/ml) against Penicillium and Mucor, respectively. The results of this study suggest a promising multifunctional potential of this LDH for water and wastewater treatment and disinfection applications., (© 2023. The Author(s).)

Germ cells differentiate into oocytes that launch the next generation upon fertilization. How the highly specialized oocyte acquires this distinct cell fate is poorly understood. During Drosophila oogenesis, H3K9me3 histone methyltransferase SETDB1 translocates from the cytoplasm to the nucleus of germ cells concurrently with oocyte specification. Here, we discovered that nuclear SETDB1 is required for silencing a cohort of differentiation-promoting genes by mediating their heterochromatinization. Intriguingly, SETDB1 is also required for upregulating 18 of the ∼30 nucleoporins (Nups) that compose the nucleopore complex (NPC), promoting NPC formation. NPCs anchor SETDB1-dependent heterochromatin at the nuclear periphery to maintain H3K9me3 and gene silencing in the egg chambers. Aberrant gene expression due to the loss of SETDB1 or Nups results in the loss of oocyte identity, cell death, and sterility. Thus, a feedback loop between heterochromatin and NPCs promotes transcriptional reprogramming at the onset of oocyte specification, which is critical for establishing oocyte identity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Stem cells in many systems, including Drosophila germline stem cells (GSCs), increase ribosome biogenesis and translation during terminal differentiation. Here, we show that the H/ACA small nuclear ribonucleoprotein (snRNP) complex that promotes pseudouridylation of ribosomal RNA (rRNA) and ribosome biogenesis is required for oocyte specification. Reducing ribosome levels during differentiation decreased the translation of a subset of messenger RNAs that are enriched for CAG trinucleotide repeats and encode polyglutamine-containing proteins, including differentiation factors such as RNA-binding Fox protein 1. Moreover, ribosomes were enriched at CAG repeats within transcripts during oogenesis. Increasing target of rapamycin (TOR) activity to elevate ribosome levels in H/ACA snRNP complex-depleted germlines suppressed the GSC differentiation defects, whereas germlines treated with the TOR inhibitor rapamycin had reduced levels of polyglutamine-containing proteins. Thus, ribosome biogenesis and ribosome levels can control stem cell differentiation via selective translation of CAG repeat-containing transcripts.

The ability of ribosomes to translate mRNAs into proteins is the basis of all life. While ribosomes are essential for cell viability, reduction in levels of ribosomes can affect cell fate and developmental transitions in a tissue specific manner and can cause a plethora of related diseases called ribosomopathies. How dysregulated ribosomes homeostasis influences cell fate and developmental transitions is not fully understood. Model systems such as Drosophila and C. elegans oogenesis have been used to address these questions since defects in conserved steps in ribosome biogenesis result in stem cell differentiation and developmental defects. In this review, we first explore how ribosome levels affect stem cell differentiation. Second, we describe how ribosomal modifications and incorporation of ribosomal protein paralogs contribute to development. Third, we summarize how cells with perturbed ribosome biogenesis are sensed and eliminated during organismal growth., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prashanth Rangan reports financial support was provided by National Institutes of Health., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Under nutrition and overweight typically occur during nutritional transition periods in developing countries including Egypt. Short stature and anemia are public health concern due to its strong link with malnutrition which is a preventable risk factor., Objectives: to estimate the prevalence of overweight, obesity, underweight and short stature and its concurrence with anemia, also to determine the etiological profile of short stature among primary school children in Egypt., Methods: A cross-sectional study was carried out on 33,150 Egyptian children aged 6-11 years old from January 2018 to January 2020, allocated in 59 primary schools from diverse geographical districts in Egypt. Complete anthropometric measurements were conducted and applied according to WHO growth charts. Hemoglobin level was measured. Systematic approach to detect the etiology of short stature was applied randomly to a sample of 380 stunted children., Results: The prevalence of underweight was 8.2%, while obesity and overweight represented 21.8% (9.6 and 12.2% respectively). Overall short stature constituted 17%. The main etiologies of short stature were familial (40.8%) and constitutional (24.2%). Anemia was diagnosed in 26% of children; while concurrent anemia and stunting was reported in 9.9%. Regarding anemia and anemia with stunting were more common among girls (30.0% (OR = 1.50, CI95%: 1.43-1.58) and 11.4% (OR = 1.39, CI95%:1.29-1.49) respectively), who were living in rural areas (33.4% (OR = 1.96, CI 95%:1.87-2.06) &12.7% (OR = 1.72, CI 95%:1.60-1.85)) and those who had low socioeconomic status)34.6% (OR = 2.54, CI 95%:2.29-2.82) & 17.2% (OR = 3.32, CI 95%:2.85-3.88() respectively. Anemia with stunting was significantly higher among children aged ≥9 years old representing 12% (OR = 1.40, CI 95%:1.30-1.51)., Conclusion: Prevalence of short stature, obesity and anemia was high among primary school children in Egypt with a strong concurrence between anemia and stunting. Intensive parental health education and in-depth nutritional assessment are required.

The vitamin D receptor (VDR) and its ligand 1,25(OH) 2 D 3 (1,25D) impact differentiation and exert anti-tumor effects in many tissues, but its role in salivary gland has yet to be defined. Using immunohistochemistry (IHC), we have detected strong VDR expression in murine and human salivary gland ducts. Compared to normal gland, VDR protein expression was retained in differentiated human pleomorphic adenoma (PA) but was undetectable in undifferentiated PA and in carcinomas, suggesting deregulation of VDR during salivary cancer progression. To gain insight into the potential role of VDR in salivary cancer, we assessed the effects of vitamin D in vivo and in vitro. Despite the presence of VDR in salivary gland, chronic dietary vitamin D restriction did not alter morphology of the salivary epithelium in C57/Bl6 mice. The localization of VDR in ductal epithelium prompted us to examine the effects of 1,25D in an established cell line (mSGc) derived from normal murine submandibular gland (SMG). This previously characterized cell line consists of multiple stem, progenitor and differentiated cell types as determined by mutually exclusive cellular expression of basal, ductal and myoepithelial markers. We demonstrated VDR expression and regulation of VDR target genes Vdr and Postn by 1,25D in mSGc, indicating functional ligand-mediated transcriptional activity. The effect of VDR signaling on epithelial differentiation markers was assessed by qPCR and IHC in mSGc cells treated with 1,25D. We found that 1,25D reduced mRNA expression of the basal cell progenitor marker keratin 5 (K5) and increased expression of the differentiated ductal cell marker keratin 7 (K7). Further, we found that 1,25D significantly decreased the number of proliferating cells, including proliferating K5 + cells. Characterization of cell cycle by Muse cytometry indicated 1,25D treatment decreased cells in S, G 2 , and M phase. The inhibition of K5 + cell proliferation by 1,25D is of particular interest because K5 + basal cells contribute to a wide variety of salivary tumor types. Our studies suggest that 1,25D alters cancer-relevant progenitor and differentiation markers in the salivary gland., Competing Interests: Declaration of Competing Interest The authors declare no financial or non-financial conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)