Biology subjects

ZHANG, Y.

Publications and source records attributed to ZHANG, Y..

22 records · Page 2Linked to original sources

bioRxiv2020

Identification of Cis-Regulatory Sequences Controlling Pollen-Specific Expression of Hydroxyproline-Rich Glycoprotein Genes in Arabidopsis thaliana

Hydroxyproline-rich glycoproteins (HRGPs) are a superfamily of plant cell wall structural proteins that function in various aspects of plant growth and development, including pollen tube growth. We have previously characterized HRGP superfamily into three family members: the hyperglycosylated arabinogalactan-proteins, the moderately glycosylated extensins, and the lightly glycosylated proline-rich proteins. However, the mechanism of pollen-specific HRGP expression remains untouched. To this end, we developed an integrative analysis pipeline combining RNA-seq gene expression and promoter sequences that identified 15 transcriptional cis-regulatory motifs responsible for pollen-specific expression of HRGP in Arabidopsis Thaliana. Specifically, we mined the public RNA-seq datasets and identified 13 pollen-specific HRGP genes. Ensemble motif discovery with various filters identified 15 conserved promoter elements between Thaliana and Lyrata. Known motif analysis revealed pollen related transcription factors of GATA12 and brassinosteroid (BR) signaling pathway regulator BZR1. Lastly, we performed a machine learning regression analysis and demonstrated that the identified 15 motifs well captured the HRGP gene expression in pollen (R=0.61). In conclusion, we performed the integrative analysis as the first-of-its-kind study to identify cis-regulatory motifs in pollen-specific HRGP genes and shed light on its transcriptional regulation in pollen.

bioinformatics↗

bioRxiv2019

Overcoming tissue scattering in wide-field deep imaging by extended detection and computational reconstruction

Compared to the golden technique of point-scanning multiphoton microscopy, line-scanning temporal focusing microscopy (LTFM) is competitive in high imaging speed while maintaining tight axial confinement. However, considering its wide-field detection mode, LTFM suffers from shallow penetration depth as a result of crosstalk induced by tissue scattering. In contrast to the spatial filtering based on confocal slit detection, we propose the extended detection LTFM (ED-LTFM), the first technique to extract signals from scattered photons and thus effectively extend the imaging depth. By recording a succession of line-shape excited signals in 2D and reconstructing signals under Hessian regularization, we can push the depth limitation in scattering tissue imaging. We valid the concept with numerical simulations, and demonstrate the performance of enhanced imaging depth in in vivo imaging of mouse brains.

neuroscience↗

bioRxiv2019

Identification of Genes Regulating Cell Death in Staphylococcus aureus

Staphylococcus aureus is an opportunistic pathogen that causes acute and chronic infections. Due to S. aureus s highly resistant and persistent nature, it is paramount to identify better drug targets in order to eradicate S. aureus infections. Despite the efforts in understanding bacterial cell death, the genes and pathways of S. aureus cell death remain elusive. Here, we performed a genome-wide screen using a transposon mutant library to study the genetic mechanisms involved in S. aureus cell death. Using a precisely controlled heat-ramp and acetic acid exposure assays, mutations in 27 core genes (hsdR1, hslO, nsaS, sspA, folD, mfd, vraF, kdpB, USA300HOU_2684, 0868, 0369, 0420, 1154, 0142, 0930, 2590, 0997, 2559, 0044, 2004, 1209, 0152, 2455, 0154, 2386, 0232, 0350 involved in transporters, transcription, metabolism, peptidases, kinases, transferases, SOS response, nucleic acid and protein synthesis) caused the bacteria to be more death-resistant. In addition, we identified mutations in core 10 genes (capA, gltT, mnhG1,USA300HOU_1780, 2496, 0200, 2029, 0336, 0329, 2386, involved in transporters, metabolism, transcription, cell wall synthesis) from heat-ramp and acetic acid that caused the bacteria to be more death-sensitive or with defect in persistence. Interestingly, death-resistant mutants were more virulent than the parental strain USA300 and caused increased mortality in a Caenorhabditis elegans infection model. Conversely, death-sensitive mutants were less persistent and formed less persister cells upon exposure to different classes of antibiotics. These findings provide new insights into the mechanisms of S. aureus cell death and offer new therapeutic targets for developing more effective treatments caused by S. aureus.

microbiology↗

bioRxiv2017

Activity of Sulfa Drugs and Their Combinations against Stationary Phase B. burgdorferi in vitro

Lyme disease is a most common vector borne disease in the US. Although the majority of Lyme patients can be cured with the standard 2-4 week antibiotic treatment, at least 10-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, one possibility is that persisting organisms are not killed by current Lyme antibiotics. In our previous studies, we screened an FDA drug library and an NCI compound library on B. burgdorferi and found some drug hits including sulfa drugs as having good activity against B. burgdorferi stationary phase cells. In this study, we evaluated the relative activity of three commonly used sulfa drugs sulfamethoxazole (Smx), dapsone (Dps), sulfachlorpyridazine (Scp), and also trimethoprim (Tmp), and assessed their combinations with the commonly prescribed Lyme antibiotics for activities against B. burgdorferi stationary phase cells. Using the same molarity concentration, dapsone, sulfachlorpyridazine and trimethoprim showed very similar activity against stationary phase B. burgdorferi enriched in persisters, however, sulfamethoxazole was the least active drug among the three sulfa drugs tested. Interestingly, contrary to other bacterial systems, Tmp did not show synergy in drug combinations with the three sulfa drugs at their clinically relevant serum concentrations against B. burgdorferi. We found that sulfa drugs combined with other antibiotics were more active than their respective single drugs and that four-drug combinations were more active than three-drug combinations. Four drug combinations dapsone+minocycline+cefuroxime+azithromycin and dapsone+minocycline+cefuroxime+rifampin showed best activity against stationary phase B. burgdorferi in these sulfa drug combinations. However, these 4-sulfa drug containing combinations still had considerably less activity against B. burgdorferi stationary phase cells than the daptomycin+cefuroxime+doxycycline used as a positive control which completely eradicated B. burgdorferi stationary phase cells. Future studies are needed to evaluate and optimize the sulfa drug combinations in vitro and also in animal models.

microbiology↗