Arabidopsis seedling photomorphogenesis involves two antagonistically acting components, COP1 and HY5. COP1 specifically targets HY5 for degradation via the 26S proteasome in the dark through their direct physical interaction. Little is known regarding how light signals perceived by photoreceptors are transduced to regulate COP1. Arabidopsis has two related cryptochromes (cry1 and cry2) mediating various blue/ultraviolet-A light responses. Here we show that both photoactivated cryptochromes repress COP1 activity through a direct protein-protein contact and that this direct regulation is primarily responsible for the cryptochrome-mediated blue light regulation of seedling photomorphogenic development and genome expression profile.
On August 3, 2018, an outbreak of African swine fever in pigs was reported in China. We subjected a virus from an African swine fever–positive pig sample to phylogenetic analysis. This analysis showed that the causative strain belonged to the p72 genotype II and CD2v serogroup 8.
Platinum-based drugs are among the most active antitumor reagents in clinical practice; their application is limited by side effects and drug resistance. A novel and personalized near-infrared (NIR) light-activated nanoplatform is obtained by combining a photoactivatable platinum(IV) prodrug and a caspase imaging peptide conjugated with silica-coated upconversion-luminescent nanoparticles (UCNPs) for the remote control of antitumor platinum prodrug activation, and simultaneously for real-time imaging of apoptosis induced by activated cytotoxicity. Upon NIR light illumination, the Pt(IV) prodrug complex is activated at the surface of the nanoparticle and active components are selectively released which display cytotoxicity against human ovarian carcinoma A2780 cells and its cisplatin-resistant variant A2780cis cells. More importantly, the caspases enzymes triggered by cytotoxicity would effectively cleave the probe peptide, thereby allowing the direct imaging of apoptosis in living cells.
Bispecific antibodies (BsAbs) recognize two different epitopes. This dual specificity opens up a wide range of applications, including redirecting T cells to tumor cells, blocking two different signaling pathways simultaneously, dual targeting of different disease mediators, and delivering payloads to targeted sites. The approval of catumaxomab (anti-EpCAM and anti-CD3) and blinatumomab (anti-CD19 and anti-CD3) has become a major milestone in the development of bsAbs. Currently, more than 60 different bsAb formats exist, some of them making their way into the clinical pipeline. This review summarizes diverse formats of bsAbs and their clinical applications and sheds light on strategies to optimize the design of bsAbs.
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