Lipid rafts both in cellular membrane and viral envelope are critical for PRRSV efficient infection

AbstractPorcine reproductive and respiratory syndrome virus (PRRSV) represents a significantly economical challenge to the swine industry worldwide. In this study, we investigated the importance of cellular and viral lipid rafts in PRRSV infection. First, we demonstrated that PRRSV glycoproteins, Gp3 and Gp4, were associated with lipid rafts during viral entry, and disruption of cellular lipid rafts inhibited PRRSV entry. We also showed the raft-location of CD163, which might contribute to the glycoproteins–raft association. Subsequently, raft disruption caused a significant reduction of viral RNA production. Moreover, Nsp9 was shown to be distributed in rafts, suggesting that rafts probably serve as a platform for PRRSV replication. Finally, we confirmed that disassembly of rafts on the virus envelope may affect the integrity of PRRSV particles and cause the leakage of viral proteins, which impaired PRRSV infectivity. These findings might provide insights on our understanding of the mechanism of PRRSV infection

Antioxidant and anti-diabetic effects of caffeic acid in a rat model of diabetes

Purpose: To determine the antioxidant and anti-diabetic potential of a natural flavonoid, caffeic acid in a streptozotocin-induced diabetic rat model.Methods: Experimental diabetes was induced in Wistar rats using streptozotocin injection. Caffeic acid was administered orally on daily basis for 5 weeks. A glucometer was used to monitor fasting blood glucose levels. Insulin levels were estimated using enzyme-linked immunosorbent assay (ELISA). The antioxidant potential of caffeic acid was measured by determining the activities of superoxide dismutase (SOD) and catalase (CAT), and levels of reduced glutathione (GSH) in rat liver. Standard assays were performed to determine the lipid profile of the rats. Histopathological analysis was performed to determine differences in microscopic structures of pancreas among the different treatment groups.Results: Caffeic acid administration resulted in significant enhancement of serum insulin level, and decrease in blood glucose level of diabetic rat models (p < 0.05). Caffeic acid exerted antioxidant effects by significantly increasing GSH levels and activities of CAT and SOD (p < 0.05). Histologicalexamination of the pancreas depicted normal islet morphology under caffeic acid administration in diabetic rats.Conclusion: These results reveal the antioxidant potential and anti-diabetic effect of caffeic acid in a diabetic rat model and point towards the potential applicability of caffeic acid in the management of diabetes mellitus. Keywords: Diabetes mellitus, Streptozotocin, Caffeic acid, Phenolics, Anti-diabetic, Antioxidan

Transcriptomic and gene-family dynamic analyses reveal gene expression pattern and evolution in toxin-producing tissues of Asiatic toad (Bufo gargarizans)

Comprising a major clade of Anura, toads produce and secrete numerous toxins from both the parotoid glands behind their eyes and their dorsal skin. These toxins, made of various proteins and compounds, possess pharmacological potential to be repurposed to benefit human health. However, the detailed genetic regulation of toad toxin production is still poorly understood. A recent publication uncovering the genome of the representative Asiatic toad (Bufo gargarizans) provides a good reference to resolve this issue. In the present study, we sequenced the transcriptomes of parotoid gland, dorsal skin and liver from the Asiatic toad. Combining our data with 35 previously published transcriptomes across eight different tissues from the same species but from different locations, we constructed a comprehensive gene co-expression network of the Asiatic toad with the assistance of the reference genome assembly. We identified 2,701 co-expressed genes in the toxin-producing tissues (including parotoid gland and dorsal skin). By comparative genomic analysis, we identified 599 expanded gene families with 2,720 genes. Through overlapping these co-expressed genes in the toad toxin-producing tissues, we observed that three cytochrome P450 (Cyp) family members (Cyp27a1, Cyp2c29, and Cyp2c39) were significantly enriched in pathways related to cholesterol metabolism. Cholesterol is a critical precursor to steroids, and the known main steroidal toxins of bufadienolides are considered as the major bioactive components in the parotoid glands of Asiatic toad. We found 3-hydroxy-methylglutaryl CoA reductase (hmgcr), encoding the major rate-limiting enzyme for cholesterol biosynthesis, appears with multiple copies in both Asiatic toad and common toad, possibly originating from a tandem duplication event. The five copies of hmgcr genes consistently displayed higher transcription levels in the parotoid gland when compared with the abdominal skin, suggesting it as a vital candidate gene in the involvement of toad toxin production. Taken together, our current study uncovers transcriptomic and gene-family dynamic evidence to reveal the vital role of both expanded gene copies and gene expression changes for production of toad toxins

FedDD: Toward Communication-efficient Federated Learning with Differential Parameter Dropout

Federated Learning (FL) requires frequent exchange of model parameters, which leads to long communication delay, especially when the network environments of clients vary greatly. Moreover, the parameter server needs to wait for the slowest client (i.e., straggler, which may have the largest model size, lowest computing capability or worst network condition) to upload parameters, which may significantly degrade the communication efficiency. Commonly-used client selection methods such as partial client selection would lead to the waste of computing resources and weaken the generalization of the global model. To tackle this problem, along a different line, in this paper, we advocate the approach of model parameter dropout instead of client selection, and accordingly propose a novel framework of Federated learning scheme with Differential parameter Dropout (FedDD). FedDD consists of two key modules: dropout rate allocation and uploaded parameter selection, which will optimize the model parameter uploading ratios tailored to different clients' heterogeneous conditions and also select the proper set of important model parameters for uploading subject to clients' dropout rate constraints. Specifically, the dropout rate allocation is formulated as a convex optimization problem, taking system heterogeneity, data heterogeneity, and model heterogeneity among clients into consideration. The uploaded parameter selection strategy prioritizes on eliciting important parameters for uploading to speedup convergence. Furthermore, we theoretically analyze the convergence of the proposed FedDD scheme. Extensive performance evaluations demonstrate that the proposed FedDD scheme can achieve outstanding performances in both communication efficiency and model convergence, and also possesses a strong generalization capability to data of rare classes

IL-7 promotes T cell proliferation through destabilization of p27Kip1

Interleukin (IL)-7 is required for survival and homeostatic proliferation of T lymphocytes. The survival effect of IL-7 is primarily through regulation of Bcl-2 family members; however, the proliferative mechanism is unclear. It has not been determined whether the IL-7 receptor actually delivers a proliferative signal or whether, by promoting survival, proliferation results from signals other than the IL-7 receptor. We show that in an IL-7–dependent T cell line, cells protected from apoptosis nevertheless underwent cell cycle arrest after IL-7 withdrawal. This arrest was accompanied by up-regulation of the cyclin-dependent kinase inhibitor p27Kip1 through a posttranslational mechanism. Overexpression of p27Kip1 induced G1 arrest in the presence of IL-7, whereas knockdown of p27Kip1 by small interfering RNA promoted S phase entry after IL-7 withdrawal. CD4 or CD8 T cells transferred into IL-7–deficient hosts underwent G1 arrest, whereas 27Kip1-deficient T cells underwent proliferation. We observed that IL-7 withdrawal activated protein kinase C (PKC)θ and that inhibition of PKCθ with a pharmacological inhibitor completely blocked the rise of p27Kip1 and rescued cells from G1 arrest. The conventional pathway to breakdown of p27Kip1 is mediated by S phase kinase-associated protein 2; however, our evidence suggests that PKCθ acts via a distinct, unknown pathway inducing G1 arrest after IL-7 withdrawal from T cells. Hence, IL-7 maintains T cell proliferation through a novel pathway of p27Kip1 regulation