Biology subjects

Zhang, M.-L.

Publications and source records attributed to Zhang, M.-L..

3 recordsLinked to original sources

bioRxiv2024

Maize TIR-only Proteins ZmTIR1 and ZmTIR2, but not ZmTIR3 Confer Auto-active Hypersensitive Response Likely by Forming Condensation

Nucleotide binding, leucine-rich-repeat (NLR) proteins are the major intracellular receptors for defending against pathogen infection. The recognition between NLRs and pathogen secreted effectors often triggers a localized programmed cell death termed hypersensitive response (HR). Despite significant progresses have been achieved in understanding canonical NLRs with the N-terminal Toll/interleukin-1 receptor (TIR) domains, the molecular mechanisms underlying TIR-only proteins in plant immune responses remain unclear. In this study, we identified six TIR-containing proteins in maize, including three TIR-only proteins. Functional analysis showed that ZmTIR1 and ZmTIR2, but not ZmTIR3, confer autoactive HR when transiently expressed in N. benthamiana. The autoactivity conferred by ZmTIR1 and ZmTIR2 depends on EDS1-PAD4-RNL module and their putative NADase activities. Interestingly, ZmTIR1 and ZmTIR2 predominantly localize in the punctate dots and likely form condensation, while ZmTIR3 mainly localizes in the cytoplasm and the nucleus. Two specific amino acids in the BB-loop region were identified to be required for ZmTIR1- and ZmTIR2-mediated condensation formation and auto-HR. Furthermore, ZmTIR and ZmTIR2 are induced by Cochliobolus heterostrophus, the causal agent of southern leaf blight (SLB) in maize, and knock-down the expression of ZmTIR1 or ZmTIR2 decreased the resistance to SLB in maize. Our study reveals a novel mechanism of monocot TIR-only proteins in maize immune responses.

plant biology↗

bioRxiv2024

Genetic evolution analysis of hemagglutinin and neuraminidase genes of H9N2 avian influenza virus in external environment of some areas of Yunnan Province, China from 2020 to 2023

ObjectiveTo understand the molecular characteristics and genetic variation of hemagglutinin (HA) and neuraminidase (NA) genes of H9N2 subtype avian influenza virus (AIV) in the external environment of Yunnan Province, and to provide evidence for the prevention and control of H9N2 subtype AIV in this area. ResultsThe HA and NA genes of 20 isolates belonged to Y280-like sub-branch. The nucleotide and amino acid homology of HA gene were 88.46%-99.81% and 89.08% -99.61%, respectively. The nucleotide and amino acid homology of NA gene were 88.85%-100% and 90.09%-100%, respectively. The HA protein cleavage site of 20 isolates was PSRSSRGLF, which was consistent with the molecular characteristics of low pathogenic avian influenza virus. The 226 th and 228 th positions of the receptor binding site are all L and G, which have the ability to bind to the mammalian sialic acid -2,6 sialic acid receptor; HA protein had 7-8 glycosylation sites, and the main variation was the deletion of one site at 218 and the addition of one glycosylation site at 313 and 491. The main antigenic sites were G90E, S/T145D, D/N153G, A/S/F168N/E, T200R, N/D201G/T mutations. The NA protein neck of 20 isolates lacked 3 amino acids (TEI), which had the molecular characteristics of highly pathogenic avian influenza. NA protein had 6-8 glycosylation sites. The main variation was that two isolates increased a new glycosylation site NPTQ at the 2nd position, and one isolate increased a new glycosylation site NTTI at the 67th position. All isolates lost one site at the 402nd position, and some isolates lost at the 83rd and 365th positions. The amino acids at the active site and key site of NA protease were not mutated, and the isolates did not produce resistance to neuraminidase inhibitors. ConclusionThe HA and NA genes of H9N2 subtype avian influenza virus in Yunnan Province have evolved continuously, but they still belong to the Y280 branch of the Eurasian lineage. Mutations in key sites may cause increased infectivity and transmission. The monitoring of H9N2 subtype avian influenza virus should be strengthened to prevent it from breaking the interspecies barrier and spreading to humans and lower mammals, so as to prevent the outbreak of H9N2 subtype avian influenza.

molecular biology↗

bioRxiv2018

Short-hairpin RNA-guided single gene knockdown reverses triple-negative breast cancer

BackgroundThe origin of breast cancer remains poorly understood. Here, we testify a putative mechanism of \"breast cancer origin from inducible nitric oxide synthase (iNOS) activation and oestrogen receptor alpha (ER) inactivation\", which are classified as the essential outcomes of chronic inflammatory responses.\n\nMethodsTo reverse breast cancer status, iNOS was downregulated by short-hairpin RNA (shRNA)-guided NOS2 knockdown from human triple-negative breast cancer (TNBC) cells. To re-enact breast cancer origin, ER was downregulated by shRNA-directed ESR1 knockdown in human mammary epithelial cells.\n\nResultsUpon NOS2 knockdown from HCC1937 cells, the specific TNBC transcription factor genes, RUNX1 and BCL11A, were downregulated, hypoxia was compromised, Warburg effects were attenuated, and tumourigenic proliferation was halted, accompanied by an increase in the tumour marker cyclin D1 (CD1) and a decrease in the tumour suppressor cyclin-dependent kinase inhibitor (CKI). In contrast, ESR1 knockdown from MCF-10A cells led to upregulated BCL11A and RUNX1 expression, augmented hypoxic responses, pronounced Warburg effects, and enhanced PI3K/Akt/mTOR signalling, together with low levels of CD1 and high levels of CKI induction.\n\nConclusionsBreast cancer should originate from inflammatory signalling, during which iNOS activation and ER inactivation elicit hypoxia, oxidation, mitochondrial dysfunction, and breast cancer-like hyperplasia, demonstrating that iNOS inhibitors and ER activators represent promising candidate prodrugs enabling breast cancer prevention in the early stage.

cancer biology↗