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1.
Sci Total Environ ; 804: 150060, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34798721

RESUMO

Successful detection of SARS-COV-2 in wastewater suggests the potential utility of wastewater-based epidemiology (WBE) for COVID-19 community surveillance. This systematic review aims to assess the performance of wastewater surveillance as early warning system of COVID-19 community transmission. A systematic search was conducted in PubMed, Medline, Embase and the WBE Consortium Registry according to PRISMA guidelines for relevant articles published until 31st July 2021. Relevant data were extracted and summarized. Quality of each paper was assessed using an assessment tool adapted from Bilotta et al.'s tool for environmental science. Of 763 studies identified, 92 studies distributed across 34 countries were shortlisted for qualitative synthesis. A total of 26,197 samples were collected between January 2020 and May 2021 from various locations serving population ranging from 321 to 11,400,000 inhabitants. Overall sample positivity was moderate at 29.2% in all examined settings with the spike (S) gene having maximum rate of positive detections and nucleocapsid (N) gene being the most targeted. Wastewater signals preceded confirmed cases by up to 63 days, with 13 studies reporting sample positivity before the first cases were detected in the community. At least 50 studies reported an association of viral load with community cases. While wastewater surveillance cannot replace large-scale diagnostic testing, it can complement clinical surveillance by providing early signs of potential transmission for more active public health responses. However, more studies using standardized and validated methods are required along with risk analysis and modelling to understand the dynamics of viral outbreaks.


Assuntos
COVID-19 , Vigilância Epidemiológica Baseada em Águas Residuárias , Humanos , Saúde Pública , SARS-CoV-2 , Águas Residuárias
2.
Small ; : e2105999, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34854560

RESUMO

The double-sided electrodes with active materials are widely used for commercial lithium (Li) ion batteries with a higher energy density. Accordingly, developing an anode current collector that can accommodate the stable and homogeneous Li plating/stripping on both sides will be highly desired for practical Li metal batteries (LMBs). Herein, an integrated bidirectional porous Cu (IBP-Cu) film with a through-pore structure is fabricated as Li metal hosts using the powder sintering method. The resultant IBP-Cu current collector with tunable pore volume and size exhibits high mechanical flexibility and stability. The bidirectional and through-pore structure enables the IBP-Cu host to achieve homogeneous Li deposition and effectively suppresses the dendritic Li growth. Impressively, the as-fabricated Li/IBP-Cu anode exhibits a remarkable capacity of up to 7.0 mAh cm-2 for deep plating/stripping, outstanding rate performance, and ultralong cycling ability with high Coulombic efficiency of ≈100% for 1000 cycles. More practicably, a designed pouch cell coupled with one Li/IBP-Cu anode and two LiFePO4 cathodes exhibits a highly elevated energy density (≈187.5%) compared with a pouch cell with one anode and one cathode. Such design of a bidirectional porous Cu current collector with stable Li plating/stripping behaviors suggests its promising practical applications for next-generation Li metal batteries.

3.
Front Genet ; 12: 770014, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858482

RESUMO

Type 2C protein phosphatase (PP2C) plays an essential role in abscisic acid (ABA) signaling transduction processes. In the current study, we identify 719 putative PP2C genes in eight Rosaceae species, including 118 in Chinese white pear, 110 in European pear, 73 in Japanese apricot, 128 in apple, 74 in peach, 65 in strawberry, 78 in sweet cherry, and 73 in black raspberry. Further, the phylogenetic analysis categorized PbrPP2C genes of Chinese white pear into twelve subgroups based on the phylogenic analysis. We observed that whole-genome duplication (WGD) and dispersed gene duplication (DSD) have expanded the Rosaceae PP2C family despite simultaneous purifying selection. Expression analysis finds that PbrPP2C genes have organ-specific functions. QRT-PCR validation of nine PbrPP2C genes of subgroup A indicates a role in ABA-mediated response to abiotic stress. Finally, we find that five PbrPP2C genes of subgroup A function in the nucleus. In summary, our research suggests that the PP2C family functions to modulate ABA signals and responds to abiotic stress.

4.
J Inflamm Res ; 14: 5801-5816, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764672

RESUMO

Introduction: Alveolar epithelial tight junction damage and glycocalyx syndecan-1 (SDC-1) degrading are key factors to pulmonary edema of acute lung injury (ALI). Matrix metalloproteinase-9 (MMP-9) was involved in glycocalyx shedding, which was vital in SDC-1 degrading. This study aimed to investigate the effects of MMP-9-mediated SDC-1 shedding on tight junction in LPS-induced ALI. Methods: Mice were intratracheally atomized with 5 mg/kg LPS to stimulate different periods and LPS stimulation for 6 hours for further studies. A549 cells was stimulated for 6 hours by active MMP-9 protein to assess the effects of active MMP-9 protein on SDC-1 and tight junction. Afterward, the mice treated with MMP-9 shRNA or A549 cells were treated with MMP-9 siRNA before LPS stimulation for 6 hours to explore the effects on glycocalyx SDC-1 and tight junction. Moreover, the mice were treated with recombinant SDC-1 protein or A549 cells were over-expressed by pc-SDC-1 before LPS stimulation for 6 hours to explore the effects of SDC-1 on tight junction. Results: The mice persistent exposure to LPS showed that MMP-9 expression, glycocalyx SDC-1 shedding (SDC-1 decreased in alveolar epithelium and increased in the BALF), tight junction impairment, FITC-albumin infiltration, and other phenomena began to appear after 6 hours of LPS treatment in this study. The levels of SDC-1 and tight junction significantly decreased by active MMP-9 protein stimulation for 6 hours in the A549 cells. Therefore, LPS stimulation for six hours was selected for investigating the underlying effects of MMP-9-mediated SDC-1 shedding on the alveolar epithelial tight junction and pulmonary edema. Further vivo analysis showed that down regulation MMP-9 expression by MMP-9 shRNA significantly alleviated glycocalyx SDC-1 shedding (SDC-1 increased in alveolar epithelium and decreased in the BALF), tight junction (occludin and ZO-1) damage, and FITC-albumin infiltration in LPS-induced early ALI mice. The vitro results also showed that MMP-9 siRNA alleviated glycocalyx SDC-1 shedding (SDC-1 increased in cell culture medium and decreased in cell surface) and tight junction damage by downregulating MMP-9 expression in LPS-stimulated A549 cells. In addition, pretreatment with recombinant mouse SDC-1 protein significantly alleviated glycocalyx (SDC-1 increased in alveolar epithelium) and tight junction damage, and FITC-albumin infiltration in LPS-induced early ALI mice. Overexpression SDC-1 by pc-SDC-1 also significantly decreased tight junction damage in LPS-stimulated A549 cells. Conclusion: Glycocalyx SDC-1 shedding mediated by MMP-9 significantly aggravated tight junction damage, which further increased the pulmonary edema.

5.
Front Microbiol ; 12: 765471, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790186

RESUMO

Background and Objective: The accurate differential diagnosis of tuberculous pleural effusion (TPE) from other exudative pleural effusions is often challenging. We aimed to validate the accuracy of complement component C1q in pleural fluid (PF) in diagnosing TPE. Methods: The level of C1q protein in the PF from 49 patients with TPE and 61 patients with non-tuberculous pleural effusion (non-TPE) was quantified by enzyme-linked immunosorbent assay, and the diagnostic performance was assessed by receiver operating characteristic (ROC) curves based on the age and gender of the patients. Results: The statistics showed that C1q could accurately diagnose TPE. Regardless of age and gender, with a cutoff of 6,883.9 ng/mL, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of C1q for discriminating TPE were 0.898 (95% confidence interval: 0.825-0.947), 91.8 (80.4-97.7), 80.3 (68.2-89.4), 78.9 (69.2-86.2), and 92.5 (82.6-96.9), respectively. In subgroup analysis, the greatest diagnostic accuracy was achieved in the younger group (≤ 50 years of age) with an AUC of 0.981 (95% confidence interval: 0.899-0.999) at the cutoff of 6,098.0 ng/mL. The sensitivity, specificity, PLR, NLR, PPV, and NPV of C1q were 95.0 (83.1-99.4), 92.3 (64.0-99.8), 97.4 (85.2-99.6), and 85.7 (60.6-95.9), respectively. Conclusion: Complement component C1q protein was validated by this study to be a promising biomarker for diagnosing TPE with high diagnostic accuracy, especially among younger patients.

6.
Gene ; : 146056, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34732368

RESUMO

The Gα subunit is an important component of the heterotrimeric G-protein complex and an integral component of several signal transduction pathways. It plays crucial roles in the diverse processes of plant growth and development, including the response to abiotic stress, regulation of root development, involvement in stomatal movement, and participation in hormone responses, which have been well investigated in many species. However, no comprehensive analysis has identified and explored the evolution, expression pattern characteristics and heat stress response of the Gα subunit genes in Rosaceae. In this study, 52 Gα subunit genes were identified in eight Rosaceae species; these genes were divided into three subfamilies (I, II, and III) based on their phylogenetic, conserved motif, and structural characteristics. Whole genome and dispersed duplication events were found to have contributed significantly to the expansion of the Gα subunit gene family, and purifying selection to have played a key role in the evolution of Gα subunit genes. An expression analysis identified some PbrGPA genes that were highly expressed in leaf, root, and fruit, and exhibited diverse spatiotemporal expression models in pear. Under abiotic stress conditions, the mRNA transcript levels of PbrGPA genes were up-regulated in response to high temperature treatment in leaves. Furthermore, three Gα subunit genes were shown to be located in the plasma membrane and nucleus in pear. In conclusion, the study of the Gα subunit gene family will help us to better understand its evolutionary history and expression patterns, while facilitating further investigations into the function of the Gα subunit gene in response to heat stress.

7.
J Sci Food Agric ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34773407

RESUMO

BACKGROUND: The interfacial characteristics and in vitro digestion of emulsion were related to emulsifier type. The mean droplet diameter, ζ-potential, microstructure, interfacial tension, Quartz crystal microbalance with dissipation (QCM-D) and in vitro gastrointestinal fate of emulsions stabilized by soybean lecithin, hydrolyzed rice glutelin (HRG) and their mixture were researched. RESULTS: The value of interfacial tension was much more dramatically declined for the sample containing 20 g kg-1 of HRG. For QCM-D, a rigid layer was formed for all the samples after rinsing. The layer thickness was 0.87 ± 0.20, 2.11 ± 0.31 and 2.63 ± 0.22 nm, and adsorbed mass was 87.17 ± 10.31, 210.56 ± 20.12 and 263.09 ± 23.23 ng cm-2 , for HRG, lecithin and HRG/lecithin, respectively, indicating both HRG and lecithin were adsorbed at the oil-water interface. Structural rearrangements at the interface occurred for HRG/lecithin. The kinetics and final amount of lipid digestion depended on emulsifier type: lecithin > HRG/lecithin > HRG. These differences in digestion rate were primarily due to differences in the aggregation state of the emulsifiers. CONCLUSION: The incorporation of lecithin into HRG emulsions had better interfacial properties comparing with HRG emulsion and facilitated lipid digestibility. These results provide important information for the rational design of plant-based functional food. © 2021 Society of Chemical Industry.

8.
Int J Immunopathol Pharmacol ; 35: 20587384211040903, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34693792

RESUMO

BACKGROUND: Comprehensive bioinformatics analysis of the effective molecular screening of Podophyllum octagonal in breast cancer treatment by using network pharmacology. METHODS: We collected the active ingredients and target genes of Chinese medicine octagonal lotus through the Traditional Chinese Medicine System Pharmacology Analysis Platform (TCMSP); downloaded human protein annotation information on the protein database Uniport; and collected data from five databases: GeneCards, OMIM, PharmGkb, TDD, and DrugBank. Construct the practical ingredient-target gene data intersection to obtain the target gene-disease gene and draw the Venn diagram. We use Cytoscape 3.8.0 software to construct the effective component-target gene-disease gene network. The STRING database protein interaction (PPI) networks were erected, and we used Cytoscape 3.8.0 software to screen out its core sub-networks and hub gene networks. Through survival analysis, core genes and hub genes were screened to identify several key genes. We performed key target gene ontology (GO) analysis and gene interaction (KEGG) analysis, which were followed by molecular docking of the key active ingredients in the star anise corresponding to several key genes. RESULTS: 19 active ingredients, 444 drug targets, and 10,941 disease-related genes were obtained. The key active ingredient was quercetin. GO analysis revealed 2471 affected biological processes, and 167 pathways were obtained in KEGG enrichment analysis. CONCLUSION: This study initially screened the key active ingredients of star aniseed lotus and analyzed key genes and several essential pathways. Traditional Chinese medicine is expected to provide new evidence and research ideas to prevent and treat breast cancer.

9.
J Healthc Eng ; 2021: 4757668, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34608411

RESUMO

To conduct better research in hepatocellular carcinoma resection, this paper used 3D machine learning and logistic regression algorithm to study the preoperative assistance of patients undergoing hepatectomy. In this study, the logistic regression model was analyzed to find the influencing factors for the survival and recurrence of patients. The clinical data of 50 HCC patients who underwent extensive hepatectomy (≥4 segments of the liver) admitted to our hospital from June 2020 to December 2020 were selected to calculate the liver volume, simulated surgical resection volume, residual liver volume, surgical margin, etc. The results showed that the simulated liver volume of 50 patients was 845.2 + 285.5 mL, and the actual liver volume of 50 patients was 826.3 ± 268.1 mL, and there was no significant difference between the two groups (t = 0.425; P > 0.05). Compared with the logistic regression model, the machine learning method has a better prediction effect, but the logistic regression model has better interpretability. The analysis of the relationship between the liver tumour and hepatic vessels in practical problems has specific clinical application value for accurately evaluating the volume of liver resection and surgical margin.

10.
Front Immunol ; 12: 744477, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671356

RESUMO

Syndecan-1 (SDC-1) is a transmembrane proteoglycan of heparin sulfate that can regulate various cell signal transduction pathways in the airway epithelial cells and fibroblasts. Airway epithelial cells and human bronchial fibroblasts are crucial in airway remodeling. However, the importance of SDC-1 in the remodeling of asthmatic airways has not been confirmed yet. The present study was the first to uncover SDC-1 overexpression in the airways of humans and mice with chronic asthma. This study also validated that an increase in SDC-1 expression was correlated with TGFß1/Smad3-mediated airway remodeling in vivo and in vitro. A small interfering RNA targeting SDC-1 (SDC-1 siRNA) and homo-SDC-1 in pcDNA3.1 (pc-SDC-1) was designed to assess the effects of SDC-1 on TGFß1/Smad3-mediated collagen I expression in Beas-2B (airway epithelial cells) and HLF-1 (fibroblasts) cells. Downregulation of the SDC-1 expression by SDC-1 siRNA remarkably attenuated TGFß1-induced p-Smad3 levels and collagen I expression in Beas-2B and HLF-1 cells. In addition, SDC-1 overexpression with pc-SDC-1 enhanced TGFß1-induced p-Smad3 level and collagen I expression in Beas-2B and HLF-1 cells. Furthermore, the levels of p-Smad3 and collagen I induced by TGFß1 were slightly increased after the addition of the recombinant human SDC-1 protein to Beas-2B and HLF-1 cells. These findings in vitro were also confirmed in a mouse model. A short hairpin RNA targeting SDC-1 (SDC-1 shRNA) to interfere with SDC-1 expression considerably reduced the levels of p-Smad3 and remodeling protein (α-SMA, collagen I) in the airways induced by ovalbumin (OVA). Similarly, OVA-induced p-Smad3 and remodeling protein levels in airways increased after mice inhalation with the recombinant mouse SDC-1 protein. These results suggested that SDC-1 of airway epithelial cells and fibroblasts plays a key role in the development of airway remodeling in OVA-induced chronic asthma.

12.
BMC Plant Biol ; 21(1): 471, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654373

RESUMO

BACKGROUND: Heterotrimeric G-proteins, composed of Gα, Gß and Gγ subunits, are important signal transmitters, mediating the cellular response to multiple stimuli in animals and plants. The Gγ subunit is an essential component of the G-protein, providing appropriate functional specificity to the heterotrimer complex and has been well studied in many species. However, the evolutionary history, expression pattern and functional characteristics of Gγ subunits has not been explored in the Rosaceae, representing many important fruit crops. RESULTS: In this study, 35 Gγ subunit genes were identified from the eight species belonging to the Rosaceae family. Based on the structural gene characteristics, conserved protein motifs and phylogenetic analysis of the Gγ subunit genes, the genes were classified into three clades. Purifying selection was shown to play an important role in the evolution of Gγ subunit genes, while a recent whole-genome duplication event was the principal force determining the expansion of the Gγ subunit gene family in the subfamily Maloideae. Gγ subunit genes exhibited diverse spatiotemporal expression patterns in Chinese white pear, including fruit, root, ovary and bud, and under abiotic stress conditions, the relative expression of Gγ subunit genes were up-regulated or down-regulated. In addition, seven of the Gγ subunit proteins in pear were located on the plasma membrane, in the cytoplasm or nucleus. CONCLUSION: Overall, this study of the Gγ subunit gene family in eight Rosaceae species provided useful information to better understand the evolution and expression of these genes and facilitated further exploration of their functions in these important crop plants.


Assuntos
Subunidades gama da Proteína de Ligação ao GTP/genética , Genoma de Planta/genética , Família Multigênica/genética , Pyrus/genética , Rosaceae/genética , Motivos de Aminoácidos , Evolução Molecular , Perfilação da Expressão Gênica , Filogenia , Proteínas de Plantas/genética , Transdução de Sinais , Estresse Fisiológico
13.
Rheumatol Int ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499196

RESUMO

In view of the possible involvement of vascular endothelial growth factor-C (VEGF-C) in pathogenesis of adult-onset Still's disease (AOSD) based on our previous genome-wide association study (GWAS) results, the primary objective of this study, therefore, was to investigate the correlations between the content of VEGF-C in serum and clinical and biochemical markers of AOSD. Blood samples were collected from 80 patients with AOSD, 26 with rheumatoid arthritis (RA), 30 with systemic lupus erythematosus (SLE) and 31 healthy control subjects. The serum VEGF-C levels were determined using an enzyme-linked immunosorbent assay (ELISA). Statistical analysis and comparisons were conducted. A significantly higher serum VEGF-C level was observed in patients with AOSD than in HC. Serum VEGF-C levels had high AUC value of 0.8145 for distinguishing AOSD group from healthy group with sensitivity of 0.7097 and specificity of 0.8250. It also showed good diagnostic value to differentiate AOSD from other autoinflammatory diseases with sensitivity of 0.7500 and specificity of 0.5500. AOSD patients with fever, arthralgia, skin rash, sore throat, lymphadenopathy, splenomegaly hepatomegaly and pleuritis, had a higher level than those who did not have these symptoms (p = 0.0012, p = 0.0092, p = 0.0056, p = 0.0123, p = 0.0068, p = 0.0030, p = 0.0020, and p = 0.0018, respectively). The serum VEGF-C levels were also positively correlated with laboratory features and several cytokines related to AOSD disease activity. In conclusion, our study unveiled a close association between serum VEGF-C levels and AOSD including disease activity and clinical hematological manifestations, suggesting the potential utility of VEGF-C as a candidate biomarker to assess disease activity in AOSD.

14.
Phys Rev E ; 104(2-1): 024212, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34525534

RESUMO

The stability and superfluidity of the Bose-Einstein condensate in two-leg ladder with magnetic field are studied. The dispersion relation and the phase diagram of the system are obtained. Three phases are revealed: the Meissner phase, the biased ladder (BL) phase, and the vortex phase. The dispersion relation and phase transition of the system strongly depend on the magnitude of atomic interaction strength, the rung-to-leg coupling ratio and the magnetic flux. Particularly, the change of the energy band structure in the phase transition region is modified significantly by the atomic interaction strength. Furthermore, based on the Bogoliubov theory, the energetic and dynamical stability of the system are invested. The stability phase diagram in the full parameter space is presented, and the dependence of superfluidity on the dispersion relation is illustrated explicitly. The atomic interaction strength can produce dynamical instability in the energetic unstable region and can expand the superfluid region. The results show that the stability of the system can be controlled by the atomic interaction strength, the rung-to-leg coupling ratio and the magnetic flux. In addition, the excitation spectrums in the Meissner phase, BL phase and vortex phase are further studied. The modulation of the excitation spectrum and the energetic stability of the system by the atomic interaction strength, the rung-to-leg coupling ratio and magnetic flux is discussed. Finally, through the numerical simulation, the dynamical instability of the system is verified by the time evolution of the Bloch wave and rung current. This provides a theoretical basis for controlling the superfluidity of the system.

15.
Ecotoxicol Environ Saf ; 225: 112766, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34509967

RESUMO

Natural adjuvants are novel options to reduce the doses of chemical herbicides. The aim of the current study was to examine the compositions and adjuvant effects of rosin and coconut oil on herbicides using a combination of indoor experiment and field trial. The GC-MS results showed that the main component of rosin was abietic acid (40.02%), and the main components of coconut oil were 2-pentanone, 4-hydroxy-4-methyl- (21.45%) and dodecanoic acid (14.59%). In greenhouse experiment, rosin showed a significant adjuvant effect on nicosulfuron against Digitaria sanguinalis and Amaranthus retroflexus, with the GR50 ratios of 1.47 and 1.69, respectively. The GR50 values of nicosulfuron in the present of coconut oil were 3.99 and 10.13 g a.i./hm2 against D. sanguinalis and A. retroflexus, lower than that of individual application. The adjuvant effect of rosin and coconut oil on mesotrione was also found. In field trial, the fresh weight control efficiency of nicosulfuron (45 g a.i./hm2) and mesotrione (112.5 g a.i./hm2) was significantly improved after the addition of rosin and coconut oil, similar with that of recommended dose. Rosin and coconut oil could reduce the contact angle of nicosulfuron, with the results of 56.68° and 53.90°, respectively, lower than that of individual application. Furthermore, rosin and coconut oil could decrease the surface tension, wetting and penetration time; and increase the spreading diameter and maximum retention. Both rosin and coconut oil have adjuvant effects on herbicides in the lab & field with multiple mechanisms. Thus, they have the potential to be developed into natural adjuvants for herbicide formulation to control weeds.


Assuntos
Adjuvantes Farmacêuticos , Óleo de Coco , Cicloexanonas , Piridinas , Resinas Vegetais , Compostos de Sulfonilureia
16.
Phys Chem Chem Phys ; 23(38): 21893-21900, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34558588

RESUMO

Polymer solubility in ionic liquids (ILs) cannot be predicted by the solubility parameter approach based on the "like dissolves like" principle. According to the Kamlet-Abraham-Taft (KAT) multi-parameter polarity scale, ILs can be categorized on the basis of hydrogen-bond acidity or basicity ones. The experimental observations, that acidic ILs easily dissolve basic polymers and basic ILs dissolve acidic polymers, reflect the complementary nature of hydrogen-bonding interactions. A quantitative hydrogen-bonding analysis is proposed for predicting the solubility by taking the product of ΔαΔß as an indicator of the competition between cross-association and self-association hydrogen bonding (H-bonding), where Δα is the difference of acidity parameters between the polymer and IL, and Δß is the difference of basicity. This solubility criterion has been validated by the solubility data of 19 polymers (11 acidic and 8 basic) in 11 ILs (7 acidic and 4 basic). These principles based on KAT parameters can be applied to other systems dominated by hydrogen bonding.

17.
ACS Chem Neurosci ; 12(19): 3719-3732, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34519476

RESUMO

Protein citrullination (deimination of arginine residue) is a well-known biomarker of inflammation. Elevated protein citrullination has been shown to colocalize with extracellular amyloid plaques in postmortem AD patient brains. Amyloid-ß (Aß) peptides which aggregate and accumulate in the plaques of Alzheimer's disease (AD) have sequential N-terminal truncations and multiple post-translational modifications (PTM) such as isomerization, pyroglutamate formation, phosphorylation, nitration, and dityrosine cross-linking. However, no conclusive biochemical evidence exists whether citrullinated Aß is present in AD brains. In this study, using high-resolution mass spectrometry, we have identified citrullination of Aß in sporadic and familial AD brains by characterizing the tandem mass spectra of endogenous N-truncated citrullinated Aß peptides. Our quantitative estimations demonstrate that ∼ 35% of pyroglutamate3-Aß pool was citrullinated in plaques in the sporadic AD temporal cortex and ∼ 22% in the detergent-insoluble frontal cortex fractions. Similarly, hypercitrullinated pyroglutamate3-Aß (∼ 30%) was observed in both the detergent-soluble as well as insoluble Aß pool in familial AD cases. Our results indicate that a common mechanism for citrullination of Aß exists in both the sporadic and familial AD. We establish that citrullination of Aß is a remarkably common PTM, closely associated with pyroglutamate3-Aß formation and its accumulation in AD. This may have implications for Aß toxicity, autoantigenicity of Aß, and may be relevant for the design of diagnostic assays and therapeutic targeting.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Citrulinação , Humanos , Placa Amiloide
18.
Artigo em Inglês | MEDLINE | ID: mdl-34467643

RESUMO

The above article was posted prematurely on 31 August 2021. The article will be made fully available at a later date.

19.
Int J Mol Sci ; 22(17)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34502530

RESUMO

Fruit acidity is one of the main determinants of fruit flavor and a target trait in fruit breeding. However, the genomic mechanisms governing acidity variation among different pear varieties remain poorly understood. In this study, two pear varieties with contrasting organic acid levels, 'Dangshansuli' (low-acidity) and 'Amute' (high-acidity), were selected, and a combination of transcriptome and population genomics analyses were applied to characterize their patterns of gene expression and genetic variation. Based on RNA-seq data analysis, differentially expressed genes (DEGs) involved in organic acid metabolism and accumulation were identified. Weighted correlation network analysis (WGCNA) revealed that nine candidate TCA (tricarboxylic acid)-related DEGs and three acid transporter-related DEGs were located in three key modules. The regulatory networks of the above candidate genes were also predicted. By integrating pear resequencing data, two domestication-related genes were found to be upregulated in 'Amute', and this trend was further validated for other pear varieties with high levels of organic acid, suggesting distinct selective sweeps during pear dissemination and domestication. Collectively, this study provides insight into organic acid differences related to expression divergence and domestication in two pear varieties, pinpointing several candidate genes for the genetic manipulation of acidity in pears.


Assuntos
Ácidos Carboxílicos/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas , Pyrus/genética , RNA-Seq/métodos , Transcriptoma/genética , Ácido Cítrico/metabolismo , Frutas/genética , Frutas/metabolismo , Ontologia Genética , Redes Reguladoras de Genes , Malatos/metabolismo , Ácido Oxálico/metabolismo , Filogenia , Pyrus/classificação , Pyrus/metabolismo , Especificidade da Espécie
20.
J Alzheimers Dis Rep ; 5(1): 443-468, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368630

RESUMO

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer's disease dementia (AD)) as an 'Inception cohort' who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an 'Enrichment cohort' (as of 10 April 2019). Objective: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. Methods: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. Results: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aß-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. Conclusion: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims.

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