Sedimentary organic matter(OM) is a major reservoir of organic carbon in the global carbon cycle. Despite many studies, there still exist many debates on the mechanism of OM accumulation and preservation in marine sed...Sedimentary organic matter(OM) is a major reservoir of organic carbon in the global carbon cycle. Despite many studies, there still exist many debates on the mechanism of OM accumulation and preservation in marine sediments. We present a new field study of a Lower Cambrian shallow marine shelf sequence in the northern edge of the Yangtze Plate, China. Our results show that palynological OM and biogenic silica(Bio-Si) could be used alongside more conventional redox and paleo-productivity proxies to study the distribution of OM in marine sediments. The qualitative and quantitative study of palynological OM provides more detailed information on the nature of sedimentary organic carbon, which can be helpful in the assessment of primary productivity and OM preservation. In addition, the presence of Bio-Si stimulates the physical preservation of OM. Further analysis indicates that an increase in Bio-Si can promote OM preservation. This case-study provides insight into the intertwined factors controlling OM accumulation in the Early Cambrian.展开更多
Nod-like receptor family pyrin domain-containing protein 12 (NLRP12) is one of the critical pattern recognition receptors which participates in the regulation of multiple inflammatory responses. Mutations in NLRP12 ca...Nod-like receptor family pyrin domain-containing protein 12 (NLRP12) is one of the critical pattern recognition receptors which participates in the regulation of multiple inflammatory responses. Mutations in NLRP12 cause exceptionally rare NLRP12-associated autoinflammatory disease (NLRP12-AID). So far, very few patients with NLRP12-AID have been identified worldwide;therefore, data on the clinical phenotype and genetic profile are limited. In this study, we reported 10 patients who presented mainly with periodic fever syndrome or arthritis. Next-generation sequencing (NGS) identified 6 heterozygous mutations of NLRP12, including 2 novel null mutations. Of the patients, some with same mutations showed different clinical features. Compared to healthy controls, the increased levels of cytokines were revealed in the patients' plasmas, as well as in the supernatants of patients’ cells stimulated with lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α). The missense mutations did not change the protein expression;but decreased level of NLRP12 protein was shown in the null mutations. And in vitro expression assay demonstrated a truncating protein induced by the frameshift mutation. Further functional studies revealed the deleterious effect of mutations on nuclear factor-kappa B (NF-κB) signaling. Both the null and missense mutations impaired their inhibition of NF-κB activation induced by p65. Collectively, this study reported a relatively large NLRP12-AID case series. Our findings expand the clinical spectrum, and reinforce the diversity of genetic mutations and clinical phenotypes. The NLRP12-associated disorder should be considered when autoinflammatory diseases are encountered in the clinical practice, especially for patients presenting with periodic fever but no other genetic cause identified.展开更多
基金supported by National Natural Science Foundation of China(11047030,11171055)Soft Science Program(112400430123)Basic and Forward Position Program of Henan Provincial Science and Technology Department(122300410385)
基金supported by the National Natural Science Foundation of China(No.41430101)the State Special Fund from Ministry of Science and Technology(No.2017ZX05036002)
文摘Sedimentary organic matter(OM) is a major reservoir of organic carbon in the global carbon cycle. Despite many studies, there still exist many debates on the mechanism of OM accumulation and preservation in marine sediments. We present a new field study of a Lower Cambrian shallow marine shelf sequence in the northern edge of the Yangtze Plate, China. Our results show that palynological OM and biogenic silica(Bio-Si) could be used alongside more conventional redox and paleo-productivity proxies to study the distribution of OM in marine sediments. The qualitative and quantitative study of palynological OM provides more detailed information on the nature of sedimentary organic carbon, which can be helpful in the assessment of primary productivity and OM preservation. In addition, the presence of Bio-Si stimulates the physical preservation of OM. Further analysis indicates that an increase in Bio-Si can promote OM preservation. This case-study provides insight into the intertwined factors controlling OM accumulation in the Early Cambrian.
基金supported in part by the National Key Research and Development Program of China(No.2021YFC2702005)National Natural Science Foundation of China(No.81971547)+1 种基金the Research Fund for Outstanding Youth Scholar of Chongqing Talents(No.CQYC201905003)the High-level Medical Reserved Personnel Training Project of Chongqing(No.2019181).
文摘Nod-like receptor family pyrin domain-containing protein 12 (NLRP12) is one of the critical pattern recognition receptors which participates in the regulation of multiple inflammatory responses. Mutations in NLRP12 cause exceptionally rare NLRP12-associated autoinflammatory disease (NLRP12-AID). So far, very few patients with NLRP12-AID have been identified worldwide;therefore, data on the clinical phenotype and genetic profile are limited. In this study, we reported 10 patients who presented mainly with periodic fever syndrome or arthritis. Next-generation sequencing (NGS) identified 6 heterozygous mutations of NLRP12, including 2 novel null mutations. Of the patients, some with same mutations showed different clinical features. Compared to healthy controls, the increased levels of cytokines were revealed in the patients' plasmas, as well as in the supernatants of patients’ cells stimulated with lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α). The missense mutations did not change the protein expression;but decreased level of NLRP12 protein was shown in the null mutations. And in vitro expression assay demonstrated a truncating protein induced by the frameshift mutation. Further functional studies revealed the deleterious effect of mutations on nuclear factor-kappa B (NF-κB) signaling. Both the null and missense mutations impaired their inhibition of NF-κB activation induced by p65. Collectively, this study reported a relatively large NLRP12-AID case series. Our findings expand the clinical spectrum, and reinforce the diversity of genetic mutations and clinical phenotypes. The NLRP12-associated disorder should be considered when autoinflammatory diseases are encountered in the clinical practice, especially for patients presenting with periodic fever but no other genetic cause identified.
