Mammalian innate immune sensor STING (STimulator of INterferon Gene) was recently found to originate from bacteria. During phage infection, bacterial STING sense c-di-GMP generated by the CD-NTase ...(cGAS/DncV-like nucleotidyltransferase) encoded in the same operon and signal suicide commitment as a defense strategy that restricts phage propagation. However, the precise binding mode of c-di-GMP to bacterial STING and the specific recognition mechanism are still elusive. Here, we determine two complex crystal structures of bacterial STING/c-di-GMP, which provide a clear picture of how c-di-GMP is distinguished from other cyclic dinucleotides. The protein-protein interactions further reveal the driving force behind filament formation of bacterial STING. Finally, we group the bacterial STING into two classes based on the conserved motif in β-strand lid, which dictate their ligand specificity and oligomerization mechanism, and propose an evolution-based model that describes the transition from c-di-GMP-dependent signaling in bacteria to 2'3'-cGAMP-dependent signaling in eukaryotes.
Environmental and plant factors (soil condition, variety, season, and maturity) and exposure risks of aluminum (Al), manganese (Mn), lead (Pb), cadmium (Cd), and copper (Cu) in tea leaves were ...investigated. The concentrations of these metals in tea leaves could not be predicted by their total concentrations in the soil. During any one season, there were differences in Al, Mn, and Cd levels between tea varieties. Seasonally, autumn tea and/or summer tea had far higher levels of Al, Mn, Pb, and Cd than did spring tea. Tea leaf maturity positively correlated with the concentrations of Al, Mn, Pb, and Cd, but negatively with Cu. The calculated average daily intake doses (mg/ kg•d) for these metal elements were 0.14 (Al), 0.11 (Mn), 2.70 × 10−3 (Cu), 2.80 × 10−4 (Pb), and 2.88 × 10−6 (Cd). The hazard quotient values of each metal were all significantly lower than risk level (=1), suggesting that, for the general population, consumption of tea does not result in the intake of excessive amounts of Al, Mn, Pb, Cd, or Cu. This study identified the factors that can be monitored in the field to decrease consumer exposure to Al and Mn through tea consumption.
Practical Application
Environmental and plant factors influence aluminum and heavy metal accumulation in tea leaves. Consumers of tea are not ingesting excessive Al, Mn, Pb, Cd, or Cu. Trackable factors were identified to manage exposure levels.
Studies on the relationship between osteoporosis and intervertebral disc degeneration (IVDD) are inconsistent. Therefore, we assessed whether IVDD is affected by vertebral osteoporosis in ...ovariectomized mice and investigated the underlying pathogenesis of IVDD related to osteoporosis.
Thirty healthy female C57BL/6 J mice aged 8 weeks were randomly divided into two groups: a control group (sham operation, n = 15) and an ovariectomy group (OVX; bilateral ovariectomy, n = 15). At 12 weeks after surgery, the bone quantity and microstructure in the lumbar vertebra and endplate as well as the volume of the L4/5 disc space were evaluated by microcomputed tomography (micro-CT). The occurrence and characteristic alterations of IVDD were identified via histopathological staining. The osteoclasts were detected using tartrate-resistant acid phosphatase (TRAP) staining. Type II collagen (Col II), osterix (OSX), osteopontin (OPN), and vascular endothelial growth factor (VEGF) expression in the intervertebral disc were detected by immunohistochemical analysis.
OVX significantly increased the body weight and decreased the uterus weight. Micro-CT analysis showed that osteoporosis of the vertebra and osteochondral remodeling of the endplate were accompanied by an increase in the endplate porosity and a decrease in the disc volume in the OVX group. Likewise, histological evaluation revealed that IVDD occurred at 12 weeks after ovariectomy, with features of endochondral ossification of the endplate, loose and broken annulus fibrosus, and degeneration of nucleus pulposus. TRAP staining showed that numerous active osteoclasts appeared in the subchondral bone and cartilaginous endplate of OVX mice, whereas osteoclasts were rarely detected in control mice. Immunohistochemical analysis demonstrated that the expression of osterix was significantly increased, notably in the endplate of OVX mice. In addition, Col II was decreased in the ossification endplate and the degenerative annulus fibrosus, where OPN and VEGF expressions were elevated in OVX mice.
OVX induced vertebral osteoporosis and osteochondral remodeling of the cartilaginous endplate contributing to the angiogenesis and an increase in porosity of the bone-cartilage surface, and also affected the matrix metabolism which consequently had detrimental effects on the intervertebral disc. Our study suggests that preserving the structural integrity and the function of the adjacent structures, including the vertebrae and endplates, may protect the disc against degeneration.
Abstract
Purine-containing nucleotide second messengers regulate diverse cellular activities. Cyclic di-pyrimidines mediate anti-phage functions in bacteria; however, the synthesis mechanism remains ...elusive. Here, we determine the high-resolution structures of cyclic di-pyrimidine-synthesizing
c
GAS/
D
ncV-like
n
ucleotidyl
t
ransferases (CD-NTases) in clade E (CdnE) in its apo, substrate-, and intermediate-bound states. A conserved (R/Q)xW motif controlling the pyrimidine specificity of donor nucleotide is identified. Mutation of Trp or Arg from the (R/Q)xW motif to Ala rewires its specificity to purine nucleotides, producing mixed purine-pyrimidine cyclic dinucleotides (CDNs). Preferential binding of uracil over cytosine bases explains the product specificity of cyclic di-pyrimidine-synthesizing CdnE to cyclic di-UMP (cUU). Based on the intermediate-bound structures, a synthetic pathway for cUU containing a unique 2’3’-phosphodiester linkage through intermediate pppU3’−5’pU is deduced. Our results provide a framework for pyrimidine selection and establish the importance of conserved residues at the C-terminal loop for the specificity determination of CD-NTases.
The aim of this study was to determine the levels of fluoride in commercial teas and to estimate the contribution of tea consumption to the fluoride recommended daily allowance. A total of 558 tea ...products in 6 categories, green tea, black tea, oolong tea, pu'er tea, white tea, and reprocessed tea, were collected in the period from 2010 to 2013. The levels of fluoride in infusions of these teas were determined by a fluoride‐ion selective electrode. The mean fluoride level in all of the tea samples was 85.16 mg/kg. For each category of tea, the mean fluoride levels were 63.04, 99.74, 52.19, 101.67, 159.78, and 110.54 mg/kg for green tea, black tea, white tea, pu'er tea, oolong tea, and reprocessed tea, respectively. The fluoride content of tea from 4 tea zones in descending order were Southern tea zone (111.39 mg/kg) > Southwest tea zone (78.78 mg/kg) > Jiangnan tea zone (71.73 mg/kg) > Jiangbei tea zone (64.63 mg/kg). These areas produced teas with lower fluoride levels than available foreign‐produced tea (161.11 mg/kg). The mean chronic daily intake (CDI) was 0.02 mg/(kg•day) or 1.27 mg/kg. Generally, consuming tea from these 6 categories does not result in the intake of excessive amounts of fluoride for the general population.
Practical Application
A total of 558 tea products in 6 categories were sampled. The mean fluoride level was determined. The daily intake of fluoride through tea consumption was estimated. Tea consumption does not result in the intake of an excessive amount of fluoride for the general population.
A low‐temperature topochemical reduction strategy is used herein to prepare unconventional phosphors with luminescence covering the biological and/or telecommunications optical windows. This approach ...is demonstrated by using BiIII‐doped Y2O3 (Y2−xBixO3) as a model system. Experimental results suggest that topochemical treatment of Y2−xBixO3 using CaH2 creates randomly distributed oxygen vacancies in the matrix, resulting in the change of the oxidation states of Bi to lower oxidation states. The change of the Bi coordination environments from the BiO6 octahedra in Y2−xBixO3 to the oxygen‐deficient BiO6−z polyhedra in reduced phases leads to a shift of the emission maximum from the visible to the near‐infrared region. The generality of this approach was further demonstrated with other phosphors. Our findings suggest that this strategy can be used to explore Bi‐doped or other classes of luminescent systems, thus opening up new avenues to develop novel optical materials.
Out of the ordinary: A low‐temperature topochemical reduction strategy is used to prepare unconventional bismuth‐containing phosphors with luminescence covering the biological and/or telecommunications optical windows. CaH2 treatment of BiIII‐doped Y2O3 (Y2−xBixO3) creates randomly distributed oxygen vacancies in the matrix, leading to lowered oxidation states for the Bi centers and a change in the emission profile of the material.
Abstract 3’,5’-cyclic uridine monophosphate (cUMP) and 3’,5’-cyclic cytidine monophosphate (cCMP) have been established as bacterial second messengers in the phage defense system, named pyrimidine ...cyclase system for anti-phage resistance (Pycsar). This system consists of a pyrimidine cyclase and a cyclic pyrimidine receptor protein. However, the molecular mechanism underlying cyclic pyrimidine synthesis and recognition remains unclear. Herein, we determine the crystal structures of a uridylate cyclase and a cytidylate cyclase, revealing the conserved residues for cUMP and cCMP production, respectively. In addition, a distinct zinc-finger motif of the uridylate cyclase is identified to confer substantial resistance against phage infections. Furthermore, structural characterization of cUMP receptor protein PycTIR provides clear picture of specific cUMP recognition and identifies a conserved N-terminal extension that mediates PycTIR oligomerization and activation. Overall, our results contribute to the understanding of cyclic pyrimidine-mediated bacterial defense.
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