ALLENE OXIDE SYNTHASE (AOS) induces petal senescence through a novel JA-associated regulatory pathway in Arabidopsis.

Flowers are crucial for the reproduction of flowering plants and their senescence has drastic effects on plant-animal interactions as well as pollination. Petal senescence is the final phase of flower development which is regulated by hormones and genes. Among these, jasmonic acid (JA) has emerged as a major contributor to petal senescence, but its molecular mechanisms remain elusive. Here, the role of JA in petal senescence in Arabidopsis was investigated. We showed that petal senescence in aos mutant was significantly delayed, which also affected petal cell size and proliferation. Similar significant delays in petal senescence were observed in dad1 and coi1 mutants. However, MYB21/24 and MYC2/3/4, known downstream regulators of JA in flower development, played no role in petal senescence. This indicated that JA regulates petal senescence by modulating other unknown transcription factors. Transcriptomic analysis revealed that AOS altered the expression of 3681 genes associated, and identified groups of differentially expressed transcription factors, highlighting the potential involvement of AP-2, WRKY and NAC. Furthermore, bHLH13, bHLH17 and URH2 were identified as potential new regulators of JA-mediated petal senescence. In conclusion, our findings suggest a novel genetic pathway through which JA regulates petal senescence in Arabidopsis. This pathway operates independently of stamen development and leaf senescence, suggesting the evolution of specialized mechanisms for petal senescence. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01425-w.

Alzheimer's disease diagnostic accuracy by fluid and neuroimaging ATN framework.

OBJECTIVES: The ATN's different modalities (fluids and neuroimaging) for each of the Aß (A), tau (T), and neurodegeneration (N) elements are used for the biological diagnosis of Alzheimer's disease (AD). We aim to identify which ATN category achieves the highest potential for diagnosis and predictive accuracy of longitudinal cognitive decline. METHODS: Based on the availability of plasma ATN biomarkers (plasma-derived Aß42/40 , p-tau181, NFL, respectively), CSF ATN biomarkers (CSF-derived Aß42 /Aß40 , p-tau181, NFL), and neuroimaging ATN biomarkers (18F-florbetapir (FBP) amyloid-PET, 18F-flortaucipir (FTP) tau-PET, and fluorodeoxyglucose (FDG)-PET), a total of 2340 participants were selected from ADNI. RESULTS: Our data analysis indicates that the area under curves (AUCs) of CSF-A, neuroimaging-T, and neuroimaging-N were ranked the top three ATN candidates for accurate diagnosis of AD. Moreover, neuroimaging ATN biomarkers display the best predictive ability for longitudinal cognitive decline among the three categories. To note, neuroimaging-T correlates well with cognitive performances in a negative correlation manner. Meanwhile, participants in the "N" element positive group, especially the CSF-N positive group, experience the fastest cognitive decline compared with other groups defined by ATN biomarkers. In addition, the voxel-wise analysis showed that CSF-A related to tau accumulation and FDG-PET indexes more strongly in subjects with MCI stage. According to our analysis of the data, the best three ATN candidates for a precise diagnosis of AD are CSF-A, neuroimaging-T, and neuroimaging-N. CONCLUSIONS: Collectively, our findings suggest that plasma, CSF, and neuroimaging biomarkers differ considerably within the ATN framework; the most accurate target biomarkers for diagnosing AD were the CSF-A, neuroimaging-T, and neuroimaging-N within each ATN modality. Moreover, neuroimaging-T and CSF-N both show excellent ability in the prediction of cognitive decline in two different dimensions.

Identification of mitophagy-associated proteins profile as potential plasma biomarkers of idiopathic Parkinson's disease.

BACKGROUND: Despite extensive work to identify diagnostic plasma markers for Parkinson's disease (PD), there are still no accepted and validated surrogate biomarkers. Mitophagy-associated proteins (MAPs), including PTEN-induced putative kinase 1 (PINK1), Parkin, phosphoglycerate mutase 5 (PGAM5), BCL2 interacting protein 3 (BNIP3), and phosphorylated-TBK1 (p-TBK1), are, to our best knowledge, not well studied as a panel of biomarkers of neurodegeneration in PD. METHODS: The study population comprised 116 age-matched controls (HC), 179 PD patients, alongside and 90 PD syndromes (PDs) divided between two cohorts: (i) the modeling cohort (cohort 1), including 150 PD, 97 HC, and 80 PDs; and (ii) the validated cohort (cohort 2), including 29 PD, 19 HC, and 10 PDs. RESULTS: MAPs are elevated in the plasma of PD patients. PINK1, Parkin, and PGAM5 displayed the top three measurable increase trends in amplitude compared to BNIP3 and p-TBK1. Moreover, the area under the curve (AUC) values of PINK1, PGAM5, and Parkin were ranked the top three MAP candidates in diagnosis accuracy for PD from HC, but the MAPs make it hard to differentiate PD from PDs. In addition, there are higher plasma PINK1-Parkin levels and prominent diagnostic accuracy in A-synuclein (+) subjects than in A-synuclein (-) subjects. CONCLUSIONS: These results uncover that plasma MAPs (PINK1, Parkin, and PGAM5) may be potentially useful diagnostic biomarkers for PD diagnosis. Studies on larger cohorts would be required to test whether elevated plasma MAP levels are related to PD risk or prognosis.

Plasma-derived phosphoglycerate mutase 5 as a biomarker for Parkinson's disease.

Background: We aimed to examine whether plasma-derived phosphoglycerate mutase 5 (PGAM5) can be a biomarker for Parkinson's disease (PD) diagnosis as well as its association with the severity of motor/non-motor manifestations of PD. Methods: We enrolled 124 patients with PD (PD group) and 50 healthy controls (HC group). We measured plasma PGAM5 levels using a quantitative sandwich enzyme immunoassay. Patients with PD underwent baseline evaluations using the Unified Parkinson's Disease Rating Scale (UPDRS), while participants in both groups were evaluated using scales for non-motor manifestations. Receiver operating characteristic curves were used to evaluate the predictive utility of plasma PAMG5 alone and combined with other factors. Results: Plasma PAMG5 levels were significantly higher in the PD group; the area under the curve (AUC) of plasma PGAM5 levels alone was 0.76. The AUC values for elderly participants and patients without hypertension were 0.78 and that for was 0.79. Notably, plasma PGAM5 levels combined with plasma oligomeric α-synuclein (α-syn) and the score of the REM sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK) showed AUC values of 0.80 and 0.82. Multivariable logistic analysis revealed that plasma PAMG5 levels were independently associated with PD (odds ratio,1.875 [95% confidence interval 1.206-2.916], p = 0.005) but not the severity of motor/non-motor manifestations of PD. Conclusion: Plasma PGAM5 is an independent biomarker for PD, especially among elderly patients (age > 60 years) and patients without hypertension. The predictive utility of PGAM5 was improved when combined with plasma oligomeric α-syn or the RBDQ-HK score.

Lewy Body-Associated Proteins A-Synuclein (a-syn) as a Plasma-Based Biomarker for Parkinson's Disease.

Introduction: To explore the combined diagnostic value of plasma Lewy body-associated proteins (p-Asyn at ser129, total α-syn, and oligomeric α-syn) for the diagnosis of PD versus healthy controls (HCs) and other PD syndromes (PDs), as well as clinical characteristics prediction. Methods: This study included 145 participants: 79 patients with PD, 24 patients with PDs, and 42 HCs. A panel of plasma levels of p-Asyn, total α-syn, and oligomeric α-syn was measured by enzyme-linked immunosorbent assay (ELISA). The primary outcome was the discriminative accuracy of the combined three plasma biomarkers for PD. Results: The mean age was 65.43 (SD, 7.467) in the control group, 64.49 (SD, 8.224) in participants with PD, and 69.25 (SD, 7.952) in PDs. The plasma Lewy body-associated protein levels were significantly higher in patients with PD than in age-matched HCs, However, there was no difference in patients with PD and PDs. Of note, a combination of plasma p-Asyn, total α-syn, and oligomeric α-syn was a better biomarker for discriminating PD from HCs, with an AUC of 0.8552 (p < 0.0001, 95%CI, 0.7635-0.9409), which was significantly higher than plasma p-Asyn (ΔAUC, 0.1797), total α-syn (ΔAUC, 0.0891) and oligomeric α-syn (ΔAUC, 0.1592) alone. Meanwhile, Lewy body-associated proteins had no connections between different motor stages and dementia performances. Conclusion: Our results suggested that plasma Lewy body-associated proteins, may serve as a non-invasive biomarker to aid the diagnosis of PD from HCs. In addition, increased plasma Lewy body-associated proteins were not associated with the progression of motor and non-motor symptoms.

Serum Albumin to Globulin Ratio is Associated with the Presence and Severity of Inflammatory Bowel Disease.

Objective: Serum albumin to globulin ratio (AGR) is a marker of inflammatory disease, but its role in inflammatory bowel disease (IBD) remains unknown. The primary purpose of the present research was to explore the relationship between serum AGR and inflammatory bowel disease (IBD). Methods: A total of 179 patients with ulcerative colitis (UC), 210 patients with Crohn's disease (CD), and non-IBD controls (age- and gender-matched controls who have gastrointestinal (GI) symptoms) were enrolled in the research. Demographic data, endoscopic score, and serum biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, and Ca2+ were included. The Mayo score and the Harvey-Bradshaw Index (HBI) were applied to evaluate the disease activity of UC and CD, respectively. Results: Serum AGR was significantly lower among IBD patients compared with non-IBD controls. There was a negative association between serum AGR and Mayo score in patients with UC (r = -0.413, p < 0.001), and serum AGR was also associated with HBI score in patients with CD (r = -0.471, p < 0.001). After adjusting other potential variables, low serum AGR (below-median) was independently associated with Mayo score (ß = -0.196, p = 0.026) and HBI score (ß = -0.162, p = 0.022), respectively. The area under the curve (AUC) for AGR to distinguish UC was 0.701, and the AUC of CD was 0.759. Based on the optimal cut-off value, multivariate logistic regression indicates that low AGR can differentiate UC from non-UC (OR = 2.564, 95% CI = 1.433-4.587, p = 0.002) and CD from non-CD (OR = 3.732, 95% CI = 1.640-8.492, p = 0.001). Conclusion: AGR may become a promising candidate to help clinicians differentiate IBD and evaluate IBD disease activity. Inflammation and nutritional status might be the future directions to explore its mechanism.