Gene 33/Mig6 Inhibits Hexavalent Chromium-Induced DNA Damage and Cell Transformation in Human Lung Epithelial Cells

Hexavalent Chromium [Cr(VI)] compounds are human lung carcinogens and environmental/occupational hazards. The molecular mechanisms of Cr(VI) carcinogenesis appear to be complex and are poorly defined. In this study, we investigated the potential role of Gene 33 (ERRFI1, Mig6), a multifunctional adaptor protein, in Cr(VI)-mediated lung carcinogenesis. We show that the level of Gene 33 protein is suppressed by both acute and chronic Cr(VI) treatments in a dose- and time-dependent fashion in BEAS-2B lung epithelial cells. The inhibition also occurs in A549 lung bronchial carcinoma cells. Cr(VI) suppresses Gene 33 expression mainly through post-transcriptional mechanisms, although the mRNA level of gene 33 also tends to be lower upon Cr(VI) treatments. Cr(VI)-induced DNA damage appears primarily in the S phases of the cell cycle despite the high basal DNA damage signals at the G2M phase. Knockdown of Gene 33 with siRNA significantly elevates Cr(VI)-induced DNA damage in both BEAS-2B and A549 cells. Depletion of Gene 33 also promotes Cr(VI)-induced micronucleus (MN) formation and cell transformation in BEAS-2B cells. Our results reveal a novel function of Gene 33 in Cr(VI)-induced DNA damage and lung epithelial cell transformation. We propose that in addition to its role in the canonical EGFR signaling pathway and other signaling pathways, Gene 33 may also inhibit Cr(VI)-induced lung carcinogenesis by reducing DNA damage triggered by Cr(VI)

FedRecAttack: Model Poisoning Attack to Federated Recommendation

Federated Recommendation (FR) has received considerable popularity and attention in the past few years. In FR, for each user, its feature vector and interaction data are kept locally on its own client thus are private to others. Without the access to above information, most existing poisoning attacks against recommender systems or federated learning lose validity. Benifiting from this characteristic, FR is commonly considered fairly secured. However, we argue that there is still possible and necessary security improvement could be made in FR. To prove our opinion, in this paper we present FedRecAttack, a model poisoning attack to FR aiming to raise the exposure ratio of target items. In most recommendation scenarios, apart from private user-item interactions (e.g., clicks, watches and purchases), some interactions are public (e.g., likes, follows and comments). Motivated by this point, in FedRecAttack we make use of the public interactions to approximate users' feature vectors, thereby attacker can generate poisoned gradients accordingly and control malicious users to upload the poisoned gradients in a well-designed way. To evaluate the effectiveness and side effects of FedRecAttack, we conduct extensive experiments on three real-world datasets of different sizes from two completely different scenarios. Experimental results demonstrate that our proposed FedRecAttack achieves the state-of-the-art effectiveness while its side effects are negligible. Moreover, even with small proportion (3%) of malicious users and small proportion (1%) of public interactions, FedRecAttack remains highly effective, which reveals that FR is more vulnerable to attack than people commonly considered.Comment: This paper has been accepted by IEEE International Conference on Data Engineering 2022 (Second Research Round

Gene 33/Mig6 Regulates Apoptosis and the DNA Damage Response through Independent Mechanisms

Gene 33 (Mig6, ERRFI1) is an inducible adaptor/scaffold protein whose expression can be induced by both stress and mitogenic signals. It contains multiple domains for protein-protein interaction and is involved in a broad spectrum of cellular functions. Gene 33 promotes apoptosis in a cell type-dependent manner. A recent study has linked Gene 33 to the DNA damage response (DDR) induced by hexavalent chromium [Cr(VI)]. Here we show that Gene 33 induces apoptosis via both c-Abl/p73 and EGFR/AKT-dependent pathways in lung epithelial and lung carcinoma cells. Ectopic expression of Gene 33 also triggers DDR in an ATM-dependent fashion and through pathways with or without association with apoptosis. We observed significant presence of Gene 33 in the nucleus and chromatin. We show that the nuclear localization of Gene 33 is dependent on its 14-3-3 binding domain. We find that the chromatin localization of Gene 33 is, at least in part, dependent on its EBD motif. Our data also show that Gene 33 may regulate chromatin targeting of c-Abl and EGFR. Moreover, we observed strong association of Gene 33 with histone H2AX and that Gene 33 promotes interaction between ATM and histone H2AX without triggering DNA damage. Our study reveals novel nuclear functions of Gene 33, which mediate DDR and apoptosis through independent mechanisms. Given our previous finding that Gene 33 depletion promotes Cr(VI)-induced DNA damage, our data suggest that Gene 33 may foster DNA repair by activating DDR

Nuclear Gene 33/Mig6 Regulates the DNA Damage Response Through an ATM-dependent Mechanism

Gene 33 (Mig6, ERRFI1) is an adaptor protein with multiple cellular functions. We recently linked Gene 33 to the DNA damage response (DDR) induced by hexavalent chromium [Cr(VI)], but the molecular mechanism remains unknown. Here we show that ectopic expression of Gene 33 triggers DDR in an ATM serine/threonine kinase-dependent fashion and through pathways dependent or not dependent on ABL proto-oncogene 1 non-receptor tyrosine kinase (c-Abl). We observe clear presence of Gene 33 in the nucleus and chromatin fractions of the cell. We also found that the nuclear localization of Gene 33 is regulated by its 14-3-3 binding motif (14-3-3BD) and that the chromatin localization of Gene 33 is partially dependent on its ErbB binding domain (EBD). Our data further indicated that Gene 33 may regulate the targeting of c-Abl to chromatin. Moreover, we observed a clear association of Gene 33 with histone H2AX and that ectopic expression of Gene 33 promotes the interaction between ATM and histone H2AX without triggering DNA damage. In summary, our results reveal nuclear functions of Gene 33 that regulate DDR. The nuclear localization of Gene 33 also provides a spatial explanation on the previously reported regulation of apoptosis by Gene 33 via the c-Abl/p73 pathway. One the basis of these findings and our previous studies, we propose that Gene 33 is a proximal regulator of DDR that promotes DNA repair

Morphological Characterization of a New and Easily Recognizable Nuclear Male Sterile Mutant of Sorghum (\u3ci\u3eSorghum bicolor\u3c/i\u3e)

Sorghum (Sorghum bicolor L. Moench) is one of the most important grain crops in the world. The nuclear male sterility (NMS) trait, which is caused by mutations on the nuclear gene, is valuable for hybrid breeding and genetic studies. Several NMS mutants have been reported previously, but none of them were well characterized. Here, we present our detailed morphological characterization of a new and easily recognizable NMS sorghum mutant male sterile 8 (ms8) isolated from an elite inbred BTx623 mutagenized by ethyl methane sulfonate (EMS). Our results show that the ms8 mutant phenotype was caused by a mutation on a single recessive nuclear gene that is different from all available NMS loci reported in sorghum. In fertile sorghum plants, yellow anthers appeared first during anthesis, while in the ms8 mutant, white hairy stigma emerged first and only small white anthers were observed, making ms8 plants easily recognizable when flowering. The ovary development and seed production after manual pollination are normal in the ms8 mutant, indicating it is female fertile and male sterile only. We found that ms8 anthers did not produce pollen grains. Further analysis revealed that ms8 anthers were defective in tapetum development, which led to the arrest of pollen formation. As a stable male sterile mutant across different environments, greenhouses, and fields in different locations, the ms8 mutant could be a useful breeding tool. Moreover, ms8 might be an important for elucidating male gametophyte development in sorghum and other plants

The verticality of policy mixes for sustainability transitions: A case study of solar water heating in China

Climate change and sustainable development are the defining challenges of the modern era. The field of sustainability transitions seeks systematic solutions for fundamental transformations of socio-technical systems towards sustainability, and exploring the role of policy mixes has been a central research agenda within the field. In the extant literature, there exists a lack of both conceptual and empirical research on the vertical dimension of policy mixes for sustainability transitions. This study provides a multilevel and evolutionary interpretation of the vertical interactions of policy mixes in the process of industrial path development towards sustainability transitions. An exemplary case of solar water heating (SWH) technology in Shandong Province in China is presented, capturing both the bottom-up and top-down processes of interactions. On the one hand, urban-level policy initiatives can inform higher-level policymaking; on the other hand, national-level priorities can greatly configure policy strategies for lower-level governments. Moreover, as the industry matures, the interactions of multilevel policy mixes evolve from simpler, unidirectional patterns to more complex, bidirectional ones through a vertical policy-learning feedback mechanism. This study generates two important policy implications that extend beyond the Chinese context: first, dynamic vertical interactions between multilevel governments indicate the need to develop more nuanced perspectives on the design of policy mixes; second, policy makers need to hold a more dynamic view of policy mixes by recognizing their temporal and coevolutionary nature through the policy learning process

GmFT2a, a Soybean Homolog of FLOWERING LOCUS T, Is Involved in Flowering Transition and Maintenance

BACKGROUND: Flowering reversion can be induced in soybean (Glycine max L. Merr.), a typical short-day (SD) dicot, by switching from SD to long-day (LD) photoperiods. This process may involve florigen, putatively encoded by FLOWERING LOCUS T (FT) in Arabidopsis thaliana. However, little is known about the potential function of soybean FT homologs in flowering reversion. METHODS: A photoperiod-responsive FT homologue GmFT (renamed as GmFT2a hereafter) was cloned from the photoperiod-sensitive cultivar Zigongdongdou. GmFT2a gene expression under different photoperiods was analyzed by real-time quantitative PCR. In situ hybridization showed direct evidence for its expression during flowering-related processes. GmFT2a was shown to promote flowering using transgenic studies in Arabidopsis and soybean. The effects of photoperiod and temperature on GmFT2a expression were also analyzed in two cultivars with different photoperiod-sensitivities. RESULTS: GmFT2a expression is regulated by photoperiod. Analyses of GmFT2a transcripts revealed a strong correlation between GmFT2a expression and flowering maintenance. GmFT2a transcripts were observed continuously within the vascular tissue up to the shoot apex during flowering. By contrast, transcripts decreased to undetectable levels during flowering reversion. In grafting experiments, the early-flowering, photoperiod-insensitive stock Heihe27 promotes the appearance of GmFT2a transcripts in the shoot apex of scion Zigongdongdou under noninductive LD conditions. The photothermal effects of GmFT2a expression diversity in cultivars with different photoperiod-sensitivities and a hypothesis is proposed. CONCLUSION: GmFT2a expression is associated with flowering induction and maintenance. Therefore, GmFT2a is a potential target gene for soybean breeding, with the aim of increasing geographic adaptation of this crop