Isoprenoids are the most ancient and essential class of metabolites produced in all organisms, either via mevalonate (MVA)-and/or methylerythritol phosphate (MEP)-pathways. The MEP-pathway is present ...in all plastid-bearing organisms and most eubacteria. However, no comprehensive study reveals the origination and evolutionary characteristics of MEP-pathway genes in eukaryotes.
Here, detailed bioinformatics analyses of the MEP-pathway provide an in-depth understanding the evolutionary history of this indispensable biochemical route, and offer a basis for the co-existence of the cytosolic MVA- and plastidial MEP-pathway in plants given the established exchange of the end products between the two isoprenoid-biosynthesis pathways. Here, phylogenetic analyses establish the contributions of both cyanobacteria and Chlamydiae sequences to the plant's MEP-pathway genes. Moreover, Phylogenetic and inter-species syntenic block analyses demonstrate that six of the seven MEP-pathway genes have predominantly remained as single-copy in land plants in spite of multiple whole-genome duplication events (WGDs). Substitution rate and domain studies display the evolutionary conservation of these genes, reinforced by their high expression levels. Distinct phenotypic variation among plants with reduced expression levels of individual MEP-pathway genes confirm the indispensable function of each nuclear-encoded plastid-targeted MEP-pathway enzyme in plant growth and development.
Collectively, these findings reveal the polyphyletic origin and restrict conservation of MEP-pathway genes, and reinforce the potential function of the individual enzymes beyond production of the isoprenoids intermediates.
Metasomatic alteration of fluorapatite has been reported in several iron-oxide apatite (IOA) deposits, but its effect on elemental and isotopic variations has not been well understood. In this study, ...we present integrated elemental, U-Pb, Sr, and O isotopic microanalytical data on fresh and altered domains in fluorapatite from the Taocun IOA deposit, Eastern China, to evaluate the timing and nature of the metasomatism and its effects on the ore-forming event. Orebodies of the Taocun deposit are spatially associated with a subvolcanic, intermediate intrusion, which displays zonal alteration patterns with albite in the center and increasing actinolite, chlorite, epidote, and carbonate toward the margin. Both disseminated and vein-type ores are present in the Taocun deposit, and fluorapatite commonly occurs with magnetite and actinolite in most ores. Fluorapatite grains from the both types of ores have been variably metasomatized through a coupled dissolution-reprecipitation mechanism. Many trace elements, including Na, Cl, S, Si, Mg, Sr, U, Th, and (REEs+Y), were variably leached from the fluorapatite grains during this process and the Sr and O isotopic signatures of the grains were also modified. The altered fluorapatite grains/domains have in situ 87Sr/86Sr ratios (0.70829-0.70971) slightly higher than those of the fresh fluorapatite (0.70777-0.70868), and δ18O values (-3.0 to +3.4 ppm) variably lower than the primary domains (+5.3 to +7.5 ppm). The Sr and O isotopes of the primary fluorapatite are consistent with or slightly higher than those of the ore-hosting intrusion, implying that the early-stage, ore-forming fluids were magmatic in origin but underwent weak interaction with the country rocks. U-Pb dating of the fresh and altered domains of the fluorapatite yielded indistinguishable ages of ∼131 Ma, which are the same as the age of the ore-hosting intrusion. In combination with fluid inclusion data, we propose that the metasomatism of fluorapatite was induced by hydrothermal fluids at a late stage of the ore-forming event. The shifts to higher 87Sr/86Sr ratios and lower δ18O values in the altered fluorapatite indicate that the alteration was induced by fluids with more radioactive Sr and lighter O isotope signatures. The metasomatic fluids were likely dominated by meteoric waters that were mixed with the earlier magmatic fluids and interacted with sedimentary rocks. Our study highlights that elemental and isotopic compositions of fluorapatite can be significantly modified by hydrothermal fluids during ore-forming events. Thus, instead of traditional bulk-rock analysis, in situ microanalysis is important to provide accurate constraints on the magmatic and/or hydrothermal evolution of complex ore-forming systems.
Our current understanding of how sugar metabolism affects inflammatory pathways in macrophages is incomplete. Here, we show that glycogen metabolism is an important event that controls ...macrophage-mediated inflammatory responses. IFN-γ/LPS treatment stimulates macrophages to synthesize glycogen, which is then channeled through glycogenolysis to generate G6P and further through the pentose phosphate pathway to yield abundant NADPH, ensuring high levels of reduced glutathione for inflammatory macrophage survival. Meanwhile, glycogen metabolism also increases UDPG levels and the receptor P2Y
in macrophages. The UDPG/P2Y
signaling pathway not only upregulates the expression of STAT1 via activating RARβ but also promotes STAT1 phosphorylation by downregulating phosphatase TC45. Blockade of this glycogen metabolic pathway disrupts acute inflammatory responses in multiple mouse models. Glycogen metabolism also regulates inflammatory responses in patients with sepsis. These findings show that glycogen metabolism in macrophages is an important regulator and indicate strategies that might be used to treat acute inflammatory diseases.
In this study, we first established the doxorubicin-induced cardiotoxicity (DIC) model with C57BL/6 mice and confirmed cardiac dysfunction with transthoracic echocardiography examination. ...RNA-sequencing was then performed to explore the potential mechanisms and transcriptional changes in the process. The metabolic pathway, biosynthesis of polyunsaturated fatty acid was significantly altered in DOX-treated murine heart, and Acot1 was one of the leading-edge core genes. We then investigated the role of Acot1 to ferroptosis that was reported recently to be related to DIC. The induction of ferroptosis in the DOX-treated heart was confirmed by transmission electron microscopy, and the inhibition of ferroptosis using Fer-1 effectively prevented the cardiac injury as well as the ultrastructure changes of cardiomyocyte mitochondrial. Both in vitro and in vivo experiments proved the downregulation of Acot1 in DIC, which can be partially prevented with Fer-1 treatment. Overexpression of Acot1 in cell lines showed noteworthy protection to ferroptosis, while the knock-down of Acot1 sensitized cardiomyocytes to ferroptosis by DIC. Finally, the heart tissue of αMHC-Acot1 transgenic mice presented altered free fatty acid composition, indicating that the benefit of Acot1 in the inhibition of ferroptosis lies biochemically and relates to its enzymatic function in lipid metabolism in DIC. The current study highlights the importance of ferroptosis in DIC and points out the potential protective role of Acot1 in the process. The beneficial role of Acot1 may be related to its biochemical function by shaping the lipid composition. In all, Acot1 may become a potential treating target in preventing DIC by anti-ferroptosis.
• Organismal phylogeny provides a crucial evolutionary framework for many studies and the angiosperm phylogeny has been greatly improved recently, largely using organellar and rDNA genes. However, ...low‐copy protein‐coding nuclear genes have not been widely used on a large scale in spite of the advantages of their biparental inheritance and vast number of choices. • Here, we identified 1083 highly conserved low‐copy nuclear genes by genome comparison. Furthermore, we demonstrated the use of five nuclear genes in 91 angiosperms representing 46 orders (73% of orders) and three gymnosperms as outgroups for a highly resolved phylogeny. • These nuclear genes are easy to clone and align, and more phylogenetically informative than widely used organellar genes. The angiosperm phylogeny reconstructed using these genes was largely congruent with previous ones mainly inferred from organellar genes. Intriguingly, several new placements were uncovered for some groups, including those among the rosids, the asterids, and between the eudicots and several basal angiosperm groups. • These conserved universal nuclear genes have several inherent qualities enabling them to be good markers for reconstructing angiosperm phylogeny, even eukaryotic relationships, further providing new insights into the evolutionary history of angiosperms.
Plants flower in an appropriate season to allow sufficient vegetative development and position flower development in favorable environments. In Arabidopsis, CONSTANS (CO) and FLAVIN-BINDING KELCH ...REPEAT F-BOX1 (FKF1) promote flowering by inducing FLOWER LOCUS T (FT) expression in the long-day afternoon. The CO protein is present in the morning but could not activate FT expression due to unknown negative mechanisms, which prevent premature flowering before the day length reaches a threshold. Here, we report that TARGET OF EAT1 (TOE1) and related proteins interact with the activation domain of CO and CO-like (COL) proteins and inhibit CO activity. TOE1 binds to the FT promoter near the CO-binding site, and reducing TOE function results in a morning peak of the FT mRNA. In addition, TOE1 interacts with the LOV domain of FKF1 and likely interferes with the FKF1-CO interaction, resulting in partial degradation of the CO protein in the afternoon to prevent premature flowering.
Endometriosis (EMS) is a multifactorial disease that affects 10%-15% women of reproductive age and is associated with chronic pelvic pain and infertility. The pathogenesis of EMS has not been ...consistently explained until now. In this study, we involved 36 endometriosis patients and 14 control subjects who performed laparoscopic surgery due to gynecological benign tumor. The samples from lower third of vagina (CL), posterior vaginal fornix (CU), cervical mucus (CV), endometrium (ET) and peritoneal fluid (PF), were collected and sequenced by 16S rRNA amplicon. The continuous change of the microbiota distribution was identified along the reproductive tract. The flora in lower reproductive tract (CL, CU) were dominated by Lactobacillus. Significant difference of the community diversity began showing in the CV of EMS patients and gradually increased upward the reproductive tract. It indicates the microbiota in cervical samples is expected to be an indicator for the risk of EMS. This study also highlights the decreasing of Lactobacillus in vaginal flora and the increasing of signature Operational Taxonomic Units (OTUs) in transaction zone (CV) and upper reproductive tract (ET, PF) of EMS patients, which reflect the alteration of microbial community associated with EMS, participation of specific colonized bacteria in the EMS pathogenesis and relationship between microbiota and development of disease.
Reports on bacteria detected in maternal fluids during pregnancy are typically associated with adverse consequences, and whether the female reproductive tract harbours distinct microbial communities ...beyond the vagina has been a matter of debate. Here we systematically sample the microbiota within the female reproductive tract in 110 women of reproductive age, and examine the nature of colonisation by 16S rRNA gene amplicon sequencing and cultivation. We find distinct microbial communities in cervical canal, uterus, fallopian tubes and peritoneal fluid, differing from that of the vagina. The results reflect a microbiota continuum along the female reproductive tract, indicative of a non-sterile environment. We also identify microbial taxa and potential functions that correlate with the menstrual cycle or are over-represented in subjects with adenomyosis or infertility due to endometriosis. The study provides insight into the nature of the vagino-uterine microbiome, and suggests that surveying the vaginal or cervical microbiota might be useful for detection of common diseases in the upper reproductive tract.Whether the female reproductive tract harbours distinct microbiomes beyond the vagina has been a matter of debate. Here, the authors show a subject-specific continuity in microbial communities at six sites along the female reproductive tract, indicative of a non-sterile environment.
Explosive diversification is widespread in eukaryotes, making it difficult to resolve phylogenetic relationships. Eudicots contain c. 75% of extant flowering plants, are important for human ...livelihood and terrestrial ecosystems, and have probably experienced explosive diversifications. The eudicot phylogenetic relationships, especially among those of the Pentapetalae, remain unresolved.
Here, we present a highly supported eudicot phylogeny and diversification rate shifts using 31 newly generated transcriptomes and 88 other datasets covering 70% of eudicot orders.
A highly supported eudicot phylogeny divided Pentapetalae into two groups: one with rosids, Saxifragales, Vitales and Santalales; the other containing asterids, Caryophyllales and Dilleniaceae, with uncertainty for Berberidopsidales. Molecular clock analysis estimated that crown eudicots originated c. 146 Ma, considerably earlier than earliest tricolpate pollen fossils and most other molecular clock estimates, and Pentapetalae sequentially diverged into eight major lineages within c. 15 Myr. Two identified increases of diversification rate are located in the stems leading to Pentapetalae and asterids, and lagged behind the gamma hexaploidization.
The nuclear genes from newly generated transcriptomes revealed a well-resolved eudicot phylogeny, sequential separation of major core eudicot lineages and temporal mode of diversifications, providing new insights into the evolutionary trend of morphologies and contributions to the diversification of eudicots.
Glycogen has long been considered to have a function in energy metabolism. However, our recent study indicated that glycogen metabolism, directed by cytosolic phosphoenolpyruvate carboxykinase Pck1, ...controls the formation and maintenance of CD8
memory T (T
) cells by regulating redox homeostasis
. This unusual metabolic program raises the question of how Pck1 is upregulated in CD8
T
cells. Here, we show that mitochondrial acetyl coenzyme A is diverted to the ketogenesis pathway, which indirectly regulates Pck1 expression. Mechanistically, ketogenesis-derived β-hydroxybutyrate is present in CD8
T
cells; β-hydroxybutyrate epigenetically modifies Lys 9 of histone H3 (H3K9) of Foxo1 and Ppargc1a (which encodes PGC-1α) with β-hydroxybutyrylation, upregulating the expression of these genes. As a result, FoxO1 and PGC-1α cooperatively upregulate Pck1 expression, therefore directing the carbon flow along the gluconeogenic pathway to glycogen and the pentose phosphate pathway. These results reveal that ketogenesis acts as an unusual metabolic pathway in CD8
T
cells, linking epigenetic modification required for memory development.
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