Yeast Atg8 and its homologs are involved in autophagosome biogenesis in all eukaryotes. These are the most widely used markers for autophagy thanks to the association of their lipidated forms with autophagic membranes. The Atg8 protein family expanded in animals and plants, with most Drosophila species having two Atg8 homologs. In this Brief Report, we use clear-cut genetic analysis in Drosophila melanogaster to show that lipidated Atg8a is required for autophagy, while its non-lipidated form is essential for developmentally programmed larval midgut elimination and viability. In contrast, expression of Atg8b is restricted to the male germline and its loss causes male sterility without affecting autophagy. We find that high expression of non-lipidated Atg8b in the male germline is required for fertility. Consistent with these non-canonical functions of Atg8 proteins, loss of Atg genes required for Atg8 lipidation lead to autophagy defects but do not cause lethality or male sterility.Tumorigenesis is closely related to the disorder of the cell cycle. The cell cycle progression includes the interphase (G0/G1, S, and G2 phase) and mitosis (M phase). CCND1 is a key protein that regulates the entry of the G0/G1 phase into the S phase. In our study, we found that the short form of Fas Apoptosis Inhibitory Molecule 1 (FAIM-S) could regulate the expression of CCND1 and had a tumor-suppressing role in non-small cell lung cancer (NSCLC). https://www.selleckchem.com/products/phorbol-12-myristate-13-acetate.html Overexpressing FAIM-S significantly inhibited the proliferation and cell cycle progression in NSCLC cells. Further studies demonstrated that FAIM-S could interact with IKK-α, reducing its protein stability. This effect led to the suppression of the NF-κB pathway, resulting in the decreased expression of CCND1. Thus, our study demonstrated that FAIM-S functioned as a negative regulator of the NF-κB pathway and played a tumor-suppressing role through blocking cell cycle progression in NSCLC cells. Little is known about the efficacy of products aiming to prevent radiodermatitis, which affects between 90-95% of women with breast cancer. The use of antioxidants is promising, however, there is a lack of evidenceon their effectiveness. Here, the authors present a clinical trial protocol to evaluate the effects of applying a cream containing nanoparticles with vitamin E to prevent radiodermatitis in patients with breast cancer. The protocol recommends that 108 women with breast cancer, receiving radiotherapy, are included in this triple-blinded, randomized, controlled study at an oncology hospital. Patients will be divided in three groups of 36 individuals each group A will receive a cream with lipid nanoparticles and vitamin E, group B will receive a cream without nanoparticles nor vitamin E, and group C will receive a cream with nanoparticles without vitamin E. The primary endpoints will evaluate the incidence, degree, and time of onset of radiodermatitis. The secondary endpoints will focus on the qualotherapy treatment to two weeks after the last session. This protocol was approved by the research ethics committee of the institutions involved and registered on an international trials database.The ubiquitin-proteasome system (UPS) and autophagy-lysosomal pathway (ALP) are two major protein degradation pathways in eukaryotic cells. Initially considered as two independent pathways, there is emerging evidence that they can work in concert. As alterations of UPS and ALP function can contribute to neurodegenerative disorders, cancer and cardiac disease, there is great interest in finding targets that modulate these catabolic processes. We undertook an unbiased, total genome high-throughput screen to identify novel effectors that regulate both the UPS and ALP. We generated a stable HEK293 cell line expressing a UPS reporter (UbG76V-mCherry) and an ALP reporter (GFP-LC3) and screened for genes for which knockdown increased both UbG76V-mCherry intensity and GFP-LC3 puncta. With stringent selection, we isolated 80 candidates, including the transcription factor ZNF418 (ZFP418 in rodents). After screen validation with Zfp418 overexpression in HEK293 cells, we evaluated Zfp418 knockdown and overexpression in nutophagy adaptor 1; HEK293, human embryonic kidney cells 293; HTS, high-throughput screen; LC3, microtubule associated protein 1 light chain 3; NRVMs, neonatal rat ventricular myocytes; RNA-seq, RNA sequencing; RPS6, ribosomal protein S6; TNNI3, troponin I, cardiac 3; UPS, ubiquitin-proteasome system; shRNA, short hairpin RNA; SQSTM1/p62, sequestosome 1; VPS28, VPS28 subunit of ESCRT-I; ZNF418/ZFP418, zinc finger protein 418.The caspase-like vacuolar processing enzyme (VPE) is a key factor in programmed cell death (PCD) associated with plant stress responses. Growth medium lacking a carbon source and dark conditions caused punctate labeling of 35SVPE1-GFP (StVPE1-GFP) in potato leaves. Under conditions of carbon starvation, VPE activity and PCD symptoms strongly increased in BY-2 cells, but to a much lesser extent in VPE-RNAi BY-2 cells. During extended exposure to carbon starvation, VPE expression and activity levels peaked, with a gradual increase in BY-2 cell death. Histological analysis of StVPE1-GFP in BY-2 cells showed that carbon starvation induces its translocation from the endoplasmic reticulum to the central vacuole through tonoplast engulfment. Exposure of BY-2 culture to the macroautophagy/autophagy inhibitor concanamycin A led to, along with an accumulation of autophagic bodies, accumulation of StVPE1-GFP in the cell vacuole. This accumulation did not occur in the presence of 3-methyladenine, an inhibitor of early-stage autophagy. BY-2 cells constitutively expressing RFP-StATG8IL, an autophagosome marker, showed colocalization with the StVPE1-GFP protein in the cytoplasm and vacuole. RNAi silencing of the core autophagy component ATG4 in BY-2 cells reduced VPE activity and cell death. These results are the first to suggest that VPE translocates to the cell vacuole through the autophagy pathway, leading to PCD. Abbreviations ATG autophagy related; CLP caspase-like protease; HR hypersensitive response; PCD programmed cell death; St Solanum tuberosum; VPE vacuolar processing enzyme.