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1.
Cell Rep ; 42(8): 112852, 2023 08 29.
Article in English | MEDLINE | ID: mdl-37481718

ABSTRACT

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a major mediator of inflammation following stimulation with >45 bp double-stranded DNA (dsDNA). Herein, we identify a class of ∼20-40 bp small cytosolic dsDNA (scDNA) molecules that compete with long dsDNA (200-1,500 bp herring testis [HT]-DNA) for binding to cGAS, thus repressing HT-DNA-induced cGAS activation. The scDNA promotes cGAS and Beclin-1 interaction, releasing Rubicon, a negative regulator of phosphatidylinositol 3-kinase class III (PI3KC3), from the Beclin-1-PI3KC3 complex. This leads to PI3KC3 activation and induces autophagy, causing degradation of STING and long cytosolic dsDNA. Moreover, DNA damage decreases, and autophagy inducers increase scDNA levels. scDNA transfection and treatment with autophagy inducers attenuate DNA damage-induced cGAS activation. Thus, scDNA molecules serve as effective brakes for cGAS activation, preventing excessive inflammatory cytokine production following DNA damage. Our findings may have therapeutic implications for cytosolic DNA-associated inflammatory diseases.


Subject(s)
DNA , Membrane Proteins , Male , Humans , Beclin-1 , Membrane Proteins/metabolism , DNA/metabolism , Nucleotidyltransferases/metabolism , Phosphatidylinositol 3-Kinase , Autophagy
2.
ACS Macro Lett ; 10(6): 690-696, 2021 Jun 15.
Article in English | MEDLINE | ID: mdl-35549093

ABSTRACT

A chiral liquid crystalline elastomer (CLCE) actuator is demonstrated. The solution-cast polydomain film of CLCE can twist upon order-disorder phase transition without any preset alignment of mesogens. The handedness of twisting is specific to the molecular chirality of the chiral dopant in the CLCE structure, while the degree of twisting, in terms of helical pitch and diameter, is sensitive to the aspect ratio and the thickness of the CLCE strip as well as the chiral dopant content. This phenomenon appears to stem from the local twisting forces and deformations of randomly oriented helical domains, which cannot cancel each other out due to the chirality and thus result in a macroscopic "chiral" force acting on the CLCE actuator. This finding reveals a materials design for preparing twisting LCE actuators.

3.
Plant Sci ; 259: 12-23, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28483050

ABSTRACT

Chitinases function in the digestion of chitin molecules, which are present principally in insects and fungi. In plants, chitinase genes play important roles in defense, and their expression can be triggered in response to both biotic and abiotic stresses. In this study, we cloned and characterized an endochitinase (VDECH) from Verticillium dahliae, strain Vd080. The VDECH coding region consists of 1845bp with two exons and one 54bp intron, encoding a 615 amino acid protein with the predicted molecular weight (MW) of 63.9kDa. The VDECH cDNA without signal peptide-encoding region was introduced into pCold-TF vector and the recombinant protein HIS-VDECH with a predicted MW of ∼114kDa was expressed. HIS-VDECH showed high tolerance to extreme temperature, exhibiting efficient chitinolytic activity at 50°C. In addition, VDECH triggered typical plant defense responses, including a hypersensitive response, oxidative burst, and elicited increased expression of defense-related genes in both Arabidopsis and cotton. VDECH-treatment of the conidial spores of V. dahliae and Fusarium oxysporum resulted in marked reductions in the germination of these spores in both fungi. After 36h of incubation with VDECH, the inhibition rate of germination was recorded at 99.57% for V. dahliae, and 96.89% for F. oxysporum. These results provide evidence that VDECH is recognized by the plant to elicit defense responses, and also that VDECH is an effective inhibitor of conidia germination, both of which may be exploited for disease control.


Subject(s)
Chitinases/metabolism , Spores, Fungal/enzymology , Spores, Fungal/immunology , Verticillium/enzymology , Verticillium/immunology , Chitinases/genetics , Gene Expression Regulation, Plant/genetics , Gene Expression Regulation, Plant/immunology , Plant Diseases/immunology , Plant Diseases/microbiology , Plant Immunity/immunology , Spores, Fungal/pathogenicity , Verticillium/pathogenicity
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