Biology subjects

Cen, Y.

Publications and source records attributed to Cen, Y..

4 recordsLinked to original sources

bioRxiv2024

Biochemical Characterization and Inhibitor Discovery for PfSir2A -- New Tricks for An Old Enzyme

The Sir2 enzyme from Plasmodium falciparum (PfSir2A) is essential for the antigenic variation of this parasite, and its inhibition is expected to have therapeutic effects for malaria. Selective PfSir2A inhibitors are not available yet, partially due to the fact that this enzyme demonstrates extremely weak in vitro deacetylase activity, making the characterization of its inhibitors rather challenging. In the current study, we report the biochemical characterization and inhibitor discovery for this enzyme. PfSir2A exhibits greater enzymatic activity in the presence of DNA for both the peptide and histone protein substrates, suggesting that nucleosomes may be the real substrates of this enzyme. Indeed, it demonstrates robust deacetylase activity against nucleosome substrates, stemming primarily from the tight binding interactions with the nucleosome. In addition to DNA/nucleosome, free fatty acids (FFAs) are also identified as endogenous PfSir2A regulators. Myristic acid, a biologically relevant FFA, shows differential regulation of the two distinct activities of PfSir2A: activates deacetylation, but inhibits defatty-acylation. The structural basis of this differential regulation was further explored. Moreover, synthetic small molecule inhibitors of PfSir2A were discovered through the screening of a library of human sirtuin regulators. The mechanism of inhibition of the lead compounds were investigated. Collectively, the mechanistic insights and inhibitors described in this study will facilitate the future development of small molecule PfSir2A inhibitors as antimalarial agents.

biochemistry↗

bioRxiv2023

Adipokinetic hormone signaling mediates the fecundity of Diaphorina citri infected by Candidatus Liberibacter asiaticus

Diaphorina citri serves as the primary vector for Candidatus Liberibacter asiaticus (CLas), the bacterium associated with the severe Asian form of huanglongbing. CLas-positive D. citri are more fecund than their CLas-negative counterparts and require extra energy expenditure. Therefore, understanding the molecular mechanisms linking metabolism and reproduction is of particular importance. In this study, we found adipokinetic hormone (DcAKH) and its receptor (DcAKHR) were essential for increasing lipid metabolism and fecundity in response to CLas infection in D. citri. Knockdown of DcAKH and DcAKHR not only resulted in the accumulation of triacylglycerol and a decline of glycogen, but also significantly decreased fecundity and CLas titer in ovaries. Combined in vivo and in vitro experiments showed that miR-34 suppresses DcAKHR expression by binding to its 3 untranslated region, whilst overexpression of miR-34 resulted in a decline of DcAKHR expression and CLas titer in ovaries and caused defects that mimicked DcAKHR knockdown phenotypes. Additionally, knockdown of DcAKH and DcAKHR significantly reduced juvenile hormone (JH) titer and JH signaling pathway genes in fat bodies and ovaries, including the JH receptor, methoprene-tolerant (DcMet), and the transcription factor, Kruppel homolog 1 (DcKr-h1), that acts downstream of it, as well as the egg development related genes vitellogenin 1-like (DcVg-1-like), vitellogenin A1-like (DcVg-A1-like) and the vitellogenin receptor (DcVgR). As a result, CLas hijacks AKH/AKHR-miR-34-JH signaling to improve D. citri lipid metabolism and fecundity, while simultaneously increasing the replication of CLas, suggesting a mutualistic interaction between CLas and D. citri ovaries.

ecology↗

bioRxiv2022

Bright and sensitive red voltage indicators for imaging action potentials in brain slices and pancreatic islets

As fast developing tools for observing cellular membrane potential, red-emitting genetically encoded voltage indicators (GEVIs) reduce auto-fluorescence background, allow multiplexed recordings, and enable all-optical electrophysiology, but have been limited by either insensitivity or dimness. Here, we report a pair of red GEVIs, Cepheid1b/s, with improved sensitivity, brightness, and photostability. Cepheid1 indicators faithfully report cellular excitability in pancreatic islets and neural activity in acute brain slices.

neuroscience↗

bioRxiv2022

scCDC: a computational method for gene-specific contamination detection and correction in single-cell and single-nucleus RNA-seq data

In droplet-based single-cell RNA-seq (scRNA-seq) and single-nucleus RNA-seq (snRNA-seq) assays, systematic contamination of ambient RNA molecules biases the estimation of genuine transcriptional levels. To correct the contamination, several computational methods have been developed. However, these methods do not distinguish the contamination-causing genes and thus either under- or over-corrected the contamination in our in-house snRNA-seq data of virgin and lactating mammary glands. Hence, we developed scCDC as the first method that specifically detects the contamination-causing genes and only corrects the expression counts of these genes. Benchmarked against existing methods on synthetic and real scRNA-seq and snRNA-seq datasets, scCDC achieved the best contamination correction accuracy with minimal data alteration. Moreover, scCDC applies to processed scRNA-seq and snRNA-seq data with empty droplets removed. In conclusion, scCDC is a flexible, accurate decontamination method that detects the contamination-causing genes, corrects the contamination, and avoids the over-correction of other genes.

bioinformatics↗