The bacterial pathogen Legionella pneumophila creates an intracellular niche permissive for its replication by extensively modulating host-cell functions using hundreds of effector proteins delivered ...by its Dot/Icm secretion system
. Among these, members of the SidE family (SidEs) regulate several cellular processes through a unique phosphoribosyl ubiquitination mechanism that bypasses the canonical ubiquitination machinery
. The activity of SidEs is regulated by another Dot/Icm effector known as SidJ
; however, the mechanism of this regulation is not completely understood
. Here we demonstrate that SidJ inhibits the activity of SidEs by inducing the covalent attachment of glutamate moieties to SdeA-a member of the SidE family-at E860, one of the catalytic residues that is required for the mono-ADP-ribosyltransferase activity involved in ubiquitin activation
. This inhibition by SidJ is spatially restricted in host cells because its activity requires the eukaryote-specific protein calmodulin (CaM). We solved a structure of SidJ-CaM in complex with AMP and found that the ATP used in this reaction is cleaved at the α-phosphate position by SidJ, which-in the absence of glutamate or modifiable SdeA-undergoes self-AMPylation. Our results reveal a mechanism of regulation in bacterial pathogenicity in which a glutamylation reaction that inhibits the activity of virulence factors is activated by host-factor-dependent acyl-adenylation.
Crystalline borates have received great attention due to their various structures and wide applications. For a long time, the corner-sharing B–O unit is considered a basic rule in borate structural ...chemistry. The Dy4B6O15 synthesized under high-pressure is the first oxoborate with edge-sharing BO4 tetrahedra, while the KZnB3O6 is the first ambient pressure borate with the edge-sharing BO4 tetrahedra. The edge-sharing connection modes greatly enrich the structural chemistry of borates and are expected to expand new applications in the future. In this review, we summarize the recent progress in crystalline borates with edge-sharing BO4 tetrahedra. We discuss the synthesis, fundamental building blocks, structural features, and possible applications of these edge-sharing borates. Finally, we also discuss the future perspectives in this field.
Acyl oximes are directly used as the acyl radical precursors in the hydroacylation reactions for the first time. In this work, acyl radicals can be effectively generated via β-scission of a ...phosphoranyl radical under photocatalytic conditions. As a result, the hydroacylation of alkenes triggered by the resulting acyl radicals leads to facile syntheses of a range of valuable ketones.
Individuals' peak bone mineral density (BMD) achieved and maintained at ages 20-40 years is the most powerful predictor of low bone mass and osteoporotic fractures later in life. The aim of this ...study was to identify metabolomic factors associated with peak BMD variation in US Caucasian women.
A total of 136 women aged 20-40 years, including 65 subjects with low and 71 with high hip BMD, were enrolled. The serum metabolites were assessed using a liquid chromatography-mass spectrometry (LC-MS) method. The partial least-squares discriminant analysis (PLS-DA) method and logistic regression models were used, respectively, to examine the associations of metabolomic profiles and individual metabolites with BMD.
The low and high BMD groups could be differentiated by the detected serum metabolites using PLS-DA (
= 0.008). A total of 14 metabolites, including seven amino acids and amino acid derivatives, five lipids (including three bile acids), and two organic acids, were significantly associated with the risk for low BMD. Most of these metabolites are novel in that they have never been linked with BMD in humans earlier. The prediction model including the newly identified metabolites significantly improved the classification of the groups with low and high BMD. The area under the receiver operating characteristic curve without and with metabolites were 0.88 (95% CI: 0.83-0.94) and 0.97 (95% CI: 0.94-0.99), respectively (
for the difference = 0.0004).
Metabolomic profiling may improve the risk prediction of osteoporosis among Caucasian women. Our findings also suggest the potential importance of the metabolism of amino acids and bile acids in bone health.
This study examined the associations between physical activity, obesity, and sarcopenia in middle-aged and older adults.
We analyzed the data of 8, 919 study participants aged between 45 to 97 (mean ...age = 57.2 ± 8.8) from a Southern state in the United States. Self-reported physical activity was classified to regular exercise ≥ 3 times/week, < 3 times/week, and no regular exercise. Associations between physical activity, obesity and sarcopenia were explored with generalized linear models and ordinal logistic regressions stratified by age (middle-aged and older adults) and gender adjusting for covariates.
In middle-aged and older adults, all examined obesity related traits (e.g., body mass index, waist circumference) were inversely associated with physical activity levels (p < 0.01) in both genders. Exercising ≥ 3 times/week was negatively associated with lean mass indicators (e.g., appendicular lean mass) in middle-aged and older females (p < 0.01), while the negative associations become positive after adjusting for weight. Positive associations between physical activity and grip strength were only found in middle-aged males (p < 0.05). Ordinal logistic regression revealed that those exercising ≥ 3 times/week were less likely to have obesity, sarcopenia, and sarcopenia obesity in all groups (p < 0.01), except for sarcopenia in older males and females (p > 0.05). Positive associations of exercising < 3 times/week with sarcopenia and sarcopenia obesity were only found in middled adults.
The associations of exercise frequency with obesity and sarcopenia vary considerably across gender and age groups. Exercise programs need to be individualized to optimize health benefits. Future research exploring physical activity strategies to balance weight reduction and lean mass maintaining is warranted in middle-aged and especially older adults.
Candida albicans is the most common human fungal pathogen and has a high propensity to develop biofilms that are resistant to traditional antifungal agents. In this study, we investigated the effect ...of tetrandrine (TET) on growth, biofilm formation and yeast-to-hypha transition of C. albicans. We characterized the inhibitory effect of TET on hyphal growth and addressed its possible mechanism of action. Treatment of TET at a low concentration without affecting fungal growth inhibited hyphal growth in both liquid and solid Spider media. Real-time RT-PCR revealed that TET down-regulated the expression of hypha-specific genes ECE1, ALS3 and HWP1, and abrogated the induction of EFG1 and RAS1, regulators of hyphal growth. Addition of cAMP restored the normal phenotype of the SC5314 strain. These results indicate that TET may inhibit hyphal growth through the Ras1p-cAMP-PKA pathway. In vivo, at a range of concentrations from 4 mg/L to 32 mg/L, TET prolonged the survival of C. albicans-infected Caenorhabditis elegans significantly. This study provides useful information for the development of new strategies to reduce the incidence of C. albicans biofilm-associated infections.
Neolamarckia cadamba is an economically-important fast-growing tree species in South China and Southeast Asia. As a prerequisite first step for future gene expression studies, we have identified and ...characterized a series of stable reference genes that can be used as controls for quantitative real time PCR (qRT-PCR) expression analysis in this study. The expression stability of 15 candidate reference genes in various tissues and mature leaves under different conditions was evaluated using four different algorithms, i.e., geNorm, NormFinder, BestKeeper and RefFinder. Our results showed that SAMDC was the most stable of the selected reference genes across the set of all samples, mature leaves at different photosynthetic cycles and under drought stress, whereas RPL10A had the most stable expression in various tissues. PGK and RPS25 were considered the most suitable reference for mature leaves at different developmental stages and under cold treatment, respectively. Additionally, the gene expression profiles of sucrose transporter 4 (NcSUT4), and 9-cis-epoxycarotenoid dioxygenase 3 (NcNCED3) were used to confirm the validity of candidate reference genes. Collectively, our study is the first report to validate the optimal reference genes for normalization under various conditions in N. cadamba and will benefit the future discovery of gene function in this species.
The polaron, a quasiparticle system formed by the interaction of electrons and phonons in quantum well (QW) materials, is very important for the photoelectric properties of low-dimensional materials. ...Therefore, the ground state binding energy (GSBE) and vibration frequency (VF) of magnetic-impurity polaron in a QW system subjected to parabolic potential in x and y directions and semi-exponential potential in z direction are studied by unitary transformation and variational method. We found that the VF and GSBE with magnetic field cyclotron frequency (MFCF), the parameter of the asymmetrical semi-exponential confinement potential (ASECP), effective confinement lengths (ECL) of the Coulombic impurity potential (CIP). The above results not only show the quantum size effect of materials but also provide a theoretical idea for regulating the polaron effect.
Background： Obesity induces dyslipidemia, hypertension, glucose intolerance, and inflammatory state, which results in atherogenic processes, diabetes, and cardiovascular disease. We usually use body ...composition indices, such as body mass index （BMI）, body fat percentage （BFP）, waist circumference-height ratio （WHtR）, and waist-hip ratio （WHR） to reflect the obesity. The aim of this large population-based cross-sectional study was to investigate the associations between body composition indices and metabolic parameters in Chinese adults. Methods： A total of 12,018 Chinese adults were included. Body composition indices, such as BMI, BFP, WHtR, and WHR, and metabolic parameters, such as systolic blood pressure （SBP）, diastolic blood pressure （DBP）, total cholesterol （TC）, triglyceride （TG）, low-density lipoprotein-cholesterol （LDL-C）, high-density lipoprotein-cholesterol （HDL-C）, fasting blood glucose （FBG）, 2 h postprandial blood glucose （2h PBG）, glycosylated hemoglobin （HbA1c）, fasting insulin （FINS）, insulin resistance index （HOMA-IR）, high-sensitivity C-reactive protein （hs-CRP）, and white blood cell count （WBC）, were measured and analyzed. All analyses were stratified by gender. Results： All body composition indices and metabolic parameters except 2h PBG differed significantly between males and females （all P 〈 0.001）. BMI was positively associated with SBP, DBP, LDL-C, TC, TG, FBG, 2h PBG, HbA1c, FINS, HOMA-IR, hs-CRP, and WBC, and inversely associated with HDL-C; similar relationships were identified between the metabolic parameters and BFP, WHtR, and WHR. In the multivariate analysis, the odds of impaired glucose regulation, dyslipidemia, insulin resistance, and increased hs-CRP were 1.36, 1.92, 3.44, and 1.27 times greater in the overweight group than those in the normal weight group, respectively, and 1.66, 3.26, 7.53, and 1.70 times greater in the obese group than those in the normal weight group, respectively. The odds of dyslipidemia and hs-CRP were 1.29 and 1.38 times greater in the BFP ≥28.0% group than in the BFP 〈28.0% group, respectively. The odds of dyslipidemia, HOMA-IR, and hs-CRP were 1.55, 1.26, and 1.48 times greater in the WHtR ≥0.96 group than in the WHtR 〈0.96 group, respectively. Among males, the odds of HOMA-IR were 1.46 times greater in the WHR ≥0.54 group than in the WHR 〈0.54 group. Similar results were observed in females. Conclusions： This study identified positive associations between all evaluated body composition indices and metabolic parameters in Chinese adults. Among the body composition indices, BMI predicted four of the five evaluated metabolic disorders in both gender groups.
Surface-enhanced Raman scattering (SERS) is a highly sensitive probe for molecular detection. The aim of this study was to develop an efficient platform for investigating the kinetics of catalytic ...reactions with SERS. To achieve this, we synthesized a novel Au–Pd bimetallic nanostructure (HIF-AuNR@AuPd) through site-specific epitaxial growth of Au–Pd alloy horns as catalytic sites at the ends of Au nanorods. Using high-resolution electron microscopy and tomography, we successfully reconstructed the complex three-dimensional morphology of HIF-AuNR@AuPd and identified that the horns are bound with high-index {11l} (0.25 < l < 0.43) facets. With an electron beam probe, we visualized the distribution of surface plasmon over the HIF-AuNR@AuPd nanorods, finding that strong longitudinal surface plasmon resonance concentrated at the rod ends. This unique crystal morphology led to the coupling of high catalytic activity with a strong SERS effect at the rod ends, making HIF-AuNR@AuPd an excellent bifunctional platform for in situ monitoring of surface catalytic reactions. Using the hydrogenation of 4-nitrothiophenol as a model reaction, we demonstrated that its first-order reaction kinetics could be accurately determined from this platform. Moreover, we clearly identified the superior catalytic activity of the rod ends relative to that of the rod bodies, owing to the different SERS activities at the two positions. In comparison with other reported Au–Pd bimetallic nanostructures, HIF-AuNR@AuPd offered both higher catalytic activity and greater detection sensitivity.
PDF
