Dear Editor,Brassinosteroids (BRs) are a class of essential polyhydroxylated steroid hormones regulating plant growth and development, and their responses to environmental cues (Clouse, 2011 ; Yang et al., 2011). ...Dear Editor,Brassinosteroids (BRs) are a class of essential polyhydroxylated steroid hormones regulating plant growth and development, and their responses to environmental cues (Clouse, 2011 ; Yang et al., 2011). BRs are perceived at the plasma membrane by a receptor complex, which consists of two leucine-rich receptor-like kinases (LRR-RLKs), BRASSINOSTEROID INSENSITIVE 1 (BRI1) and BRI1-ASSOCIATED RECEPTOR KINASE 1 (BAK1).展开更多
Sperm contributes essential paternal factors,including the paternal genome,centrosome,and oocyte-activation signals,to sexual reproduction.However,it remains unresolved how sperm contributes its RNA molecules to regul...Sperm contributes essential paternal factors,including the paternal genome,centrosome,and oocyte-activation signals,to sexual reproduction.However,it remains unresolved how sperm contributes its RNA molecules to regulate early embryonic development.Here,we show that the Caenorhabditis elegans paternal protein SPE-11 assembles into granules during meiotic divisions of spermatogenesis and later matures into a perinuclear structure where sperm RNAs localize.We reconstitute an SPE-11 liquid-phase scaffold in vitro and find that SPE-11 condensates incorporate the nematode RNA,which,in turn,promotes SPE-11 phase separation.Loss of SPE-11 does not affect sperm motility or fertilization but causes pleiotropic development defects in early embryos,and spe-11 mutant males reduce m RNA levels of genes crucial for an oocyte-to-embryo transition or embryonic development.These results reveal that SPE-11 undergoes phase separation and associates with sperm RNAs that are delivered to oocytes during fertilization,providing insights into how a paternal protein regulates early embryonic development.展开更多
Primary cilia,microtubule-based cellular protrusions found on the surface of nearly all eukaryotic cells,serve as crucial signaling hubs[1].These antenna-like organelles play a pivotal role in perceiving environmental...Primary cilia,microtubule-based cellular protrusions found on the surface of nearly all eukaryotic cells,serve as crucial signaling hubs[1].These antenna-like organelles play a pivotal role in perceiving environmental stimuli,thereby orchestrating cellular behavior and fate.Primary cilia are essential for various signaling pathways,including the Sonic Hedgehog(SHH)pathway.Ciliary dysfunction can affect multiple organ systems and manifest as a spectrum of genetic disorders collectively termed as ciliopathies.However,until recently,their involvement in circadian rhythms was unknown.展开更多
Recent studies have demonstrated that the membrane-proximal external region(MPER)of human immunodeficiency virus 1(HIV-1)glycoprotein 41 contains a series of epitopes for human monoclonal antibodies,including 2F5,Z13e...Recent studies have demonstrated that the membrane-proximal external region(MPER)of human immunodeficiency virus 1(HIV-1)glycoprotein 41 contains a series of epitopes for human monoclonal antibodies,including 2F5,Z13e1,4E10,and10E8,which were isolated from HIV-1-infected individuals and show broad neutralizing activities.This suggests that MPER is a good target for the development of effective HIV-1 vaccines.However,many studies have shown that it is difficult to induce antibodies with similar broad neutralizing activities using MPER-based peptide antigens.Here,we report that 10E8-like neutralizing antibodies with effective anti-HIV-1 activity were readily induced using a precisely designed conformational immunogenic peptide containing the 10E8-specific epitope.This immunogenic peptide(designated T10HE)contains a 15-mer MPER-derived 10E8-specific epitope fused to T-helper-cell epitopes from tetanus toxin(tt),which showed a significantly stabilized-helix structure after a series of modifications,including substitution with an(S)--(2-pentenyl)alanine containing an olefin-bearing tether and ruthenium-catalyzed olefin metathesis,compared with the unmodified T10E peptide.The stabilized-helix structure of T10HE did not affect its capacity to bind the 10E8 antibody,as evaluated with an enzyme linked immunosorbent assay(ELISA)and surface plasmon resonance binding assay(SPR assay).The efficacies of the T10HE and T10E epitope vaccines were evaluated after a standard vaccination procedure in which the experimental mice were primed with either the T10HE or T10E immunogen and boosted with HIV-1 JRFL pseudoviruses.Higher titers of 10E8-like antibodies were induced by T10HE than that by T10E.More importantly,the antibodies induced by T10HE showed enhanced antiviral potency against HIV-1 strains with both X4 and R5 tropism and a greater degree of broad neutralizing activity than the antibodies induced by T10E.These results indicate that a 10E8-epitope-based structure-specific peptide immunogen can elicit neutralizing antibodies when used as a vaccine prime.展开更多
Cilia are microtubule-based organelles projected from most eukaryotic cell surfaces performing cell motility and signaling.Several previously recognized non-ciliary proteins play crucial roles in cilium formation and ...Cilia are microtubule-based organelles projected from most eukaryotic cell surfaces performing cell motility and signaling.Several previously recognized non-ciliary proteins play crucial roles in cilium formation and function.Here,we provide additional evidence that the Caenorhabditis elegans RNA splicing factor PRP-8/PRPF8 regulates ciliogen-esis and regeneration from the ciliary base.Live imaging of GFP knock-in animals reveals that the endogenous PRP-8 localizes in the nuclei and the ciliary base.A weak loss-of-function allele of prp-8 affects ciliary structure but with little impact on RNA splicing.Conditional degradation of PRP-8 within ciliated sensory neurons showed its direct and spe-cific roles in cilium formation.Notably,the penetrance of ciliary defects correlates with the reduction of PRP-8 at the ciliary base but not nuclei,and sensory neurons regenerated cilia accompanying PRP-8 recovery from the ciliary base rather than the nuclei.We suggest that PRP-8 at the ciliary base contributes to cilium formation and regeneration.展开更多
Following publication of the original article(Xu and Ou 2022),it is reported that the supplement figure S1-S5 were missing from the article.Additional file 1:Fig.S1 contains only figure legends but no figures.
基金This work was supported by grants 91317302, 31271300, and 31430046 from the National Natural Science Foundation of China (to X.W.), by grant 2012CB114300 from the National Basic Research Program of China (to X.W.), and by a startup fund from Huazhong Agricultural University (to X.W.).We thank Wei Su (Fudan University) for critical reading of the manuscript and Zhimin Zheng and Jian-Kang Zhu (Shanghai Center for Plant Stress Biology, CAS) for providing the CRISPR/Cas9 systems. No conflict of interest declared.
文摘Dear Editor,Brassinosteroids (BRs) are a class of essential polyhydroxylated steroid hormones regulating plant growth and development, and their responses to environmental cues (Clouse, 2011 ; Yang et al., 2011). BRs are perceived at the plasma membrane by a receptor complex, which consists of two leucine-rich receptor-like kinases (LRR-RLKs), BRASSINOSTEROID INSENSITIVE 1 (BRI1) and BRI1-ASSOCIATED RECEPTOR KINASE 1 (BAK1).
基金the Ministry of Science and Technology of China(2019YFA0508401)the National Natural Science Foundation of China(31871394,82121004,32100538)+3 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)the China Postdoctoral Science Foundation(2022M711844)the Young Elite Scientists Sponsorship Program by CAST(YESS20220102)ZJ Lab and Shanghai Center for Brain Science and Brain-Inspired Technology。
文摘Sperm contributes essential paternal factors,including the paternal genome,centrosome,and oocyte-activation signals,to sexual reproduction.However,it remains unresolved how sperm contributes its RNA molecules to regulate early embryonic development.Here,we show that the Caenorhabditis elegans paternal protein SPE-11 assembles into granules during meiotic divisions of spermatogenesis and later matures into a perinuclear structure where sperm RNAs localize.We reconstitute an SPE-11 liquid-phase scaffold in vitro and find that SPE-11 condensates incorporate the nematode RNA,which,in turn,promotes SPE-11 phase separation.Loss of SPE-11 does not affect sperm motility or fertilization but causes pleiotropic development defects in early embryos,and spe-11 mutant males reduce m RNA levels of genes crucial for an oocyte-to-embryo transition or embryonic development.These results reveal that SPE-11 undergoes phase separation and associates with sperm RNAs that are delivered to oocytes during fertilization,providing insights into how a paternal protein regulates early embryonic development.
文摘Primary cilia,microtubule-based cellular protrusions found on the surface of nearly all eukaryotic cells,serve as crucial signaling hubs[1].These antenna-like organelles play a pivotal role in perceiving environmental stimuli,thereby orchestrating cellular behavior and fate.Primary cilia are essential for various signaling pathways,including the Sonic Hedgehog(SHH)pathway.Ciliary dysfunction can affect multiple organ systems and manifest as a spectrum of genetic disorders collectively termed as ciliopathies.However,until recently,their involvement in circadian rhythms was unknown.
基金supported by Ministry of Science and Technology of China(2012ZX10001-009)
文摘Recent studies have demonstrated that the membrane-proximal external region(MPER)of human immunodeficiency virus 1(HIV-1)glycoprotein 41 contains a series of epitopes for human monoclonal antibodies,including 2F5,Z13e1,4E10,and10E8,which were isolated from HIV-1-infected individuals and show broad neutralizing activities.This suggests that MPER is a good target for the development of effective HIV-1 vaccines.However,many studies have shown that it is difficult to induce antibodies with similar broad neutralizing activities using MPER-based peptide antigens.Here,we report that 10E8-like neutralizing antibodies with effective anti-HIV-1 activity were readily induced using a precisely designed conformational immunogenic peptide containing the 10E8-specific epitope.This immunogenic peptide(designated T10HE)contains a 15-mer MPER-derived 10E8-specific epitope fused to T-helper-cell epitopes from tetanus toxin(tt),which showed a significantly stabilized-helix structure after a series of modifications,including substitution with an(S)--(2-pentenyl)alanine containing an olefin-bearing tether and ruthenium-catalyzed olefin metathesis,compared with the unmodified T10E peptide.The stabilized-helix structure of T10HE did not affect its capacity to bind the 10E8 antibody,as evaluated with an enzyme linked immunosorbent assay(ELISA)and surface plasmon resonance binding assay(SPR assay).The efficacies of the T10HE and T10E epitope vaccines were evaluated after a standard vaccination procedure in which the experimental mice were primed with either the T10HE or T10E immunogen and boosted with HIV-1 JRFL pseudoviruses.Higher titers of 10E8-like antibodies were induced by T10HE than that by T10E.More importantly,the antibodies induced by T10HE showed enhanced antiviral potency against HIV-1 strains with both X4 and R5 tropism and a greater degree of broad neutralizing activity than the antibodies induced by T10E.These results indicate that a 10E8-epitope-based structure-specific peptide immunogen can elicit neutralizing antibodies when used as a vaccine prime.
基金This work was supported by the National Natural Science Foundation of China(grants 31991190,31730052,31525015,31861143042,31561130153,31671444,31871352)the National Key R&D Program of China(2017YFA0503501,2019YFA0508401,and 2017YFA0102900)。
文摘Cilia are microtubule-based organelles projected from most eukaryotic cell surfaces performing cell motility and signaling.Several previously recognized non-ciliary proteins play crucial roles in cilium formation and function.Here,we provide additional evidence that the Caenorhabditis elegans RNA splicing factor PRP-8/PRPF8 regulates ciliogen-esis and regeneration from the ciliary base.Live imaging of GFP knock-in animals reveals that the endogenous PRP-8 localizes in the nuclei and the ciliary base.A weak loss-of-function allele of prp-8 affects ciliary structure but with little impact on RNA splicing.Conditional degradation of PRP-8 within ciliated sensory neurons showed its direct and spe-cific roles in cilium formation.Notably,the penetrance of ciliary defects correlates with the reduction of PRP-8 at the ciliary base but not nuclei,and sensory neurons regenerated cilia accompanying PRP-8 recovery from the ciliary base rather than the nuclei.We suggest that PRP-8 at the ciliary base contributes to cilium formation and regeneration.
文摘Following publication of the original article(Xu and Ou 2022),it is reported that the supplement figure S1-S5 were missing from the article.Additional file 1:Fig.S1 contains only figure legends but no figures.