An atypical 3-ketoacyl ACP synthase III required for acyl homoserine lactone synthesis in Pseudomonas syringae pv. syringae B728a.

The last step of the initiation phase of fatty acid biosynthesis in most bacteria is catalyzed by the 3-ketoacyl-acyl carrier protein (ACP) synthase III (FabH). Pseudomonas syringae pv. syringae strain B728a encodes two FabH homologs, Psyr_3467 and Psyr_3830, which we designated PssFabH1 and PssFabH2, respectively. Here, we explored the roles of these two 3-ketoacyl-ACP synthase (KAS) III proteins. We found that PssFabH1 is similar to the Escherichia coli FabH in using acetyl-acetyl-coenzyme A (CoA ) as a substrate in vitro, whereas PssFabH2 uses acyl-CoAs (C4-C10) or acyl-ACPs (C6-C10). Mutant analysis showed that neither KAS III protein is essential for the de novo fatty acid synthesis and cell growth. Loss of PssFabH1 reduced the production of an acyl homoserine lactone (AHL) quorum-sensing signal, and this production was partially restored by overexpressing FabH homologs from other bacteria. AHL production was also restored by inhibiting fatty acid elongation and providing exogenous butyric acid. Deletion of PssFabH1 supports the redirection of acyl-ACP toward biosurfactant synthesis, which in turn enhances swarming motility. Our study revealed that PssFabH1 is an atypical KAS III protein that represents a new KAS III clade that functions in providing a critical fatty acid precursor, butyryl-ACP, for AHL synthesis.IMPORTANCEAcyl homoserine lactones (AHLs) are important quorum-sensing compounds in Gram-negative bacteria. Although their formation requires acylated acyl carrier proteins (ACPs), how the acylated intermediate is shunted from cellular fatty acid synthesis to AHL synthesis is not known. Here, we provide in vivo evidence that Pseudomonas syringae strain B728a uses the enzyme PssFabH1 to provide the critical fatty acid precursor butyryl-ACP for AHL synthesis. Loss of PssFabH1 reduces the diversion of butyryl-ACP to AHL, enabling the accumulation of acyl-ACP for synthesis of biosurfactants that contribute to bacterial swarming motility. We report that PssFabH1 and PssFabH2 each encode a 3-ketoacyl-acyl carrier protein synthase (KAS) III in P. syringae B728a. Whereas PssFabH2 is able to function in redirecting intermediates from ß-oxidation to fatty acid synthesis, PssFabH1 is an atypical KAS III protein that represents a new KAS III clade based on its sequence, non-involvement in cell growth, and novel role in AHL synthesis.

Risk factors associated with the prevalence of thyroid nodules in adults in Northeast China: a cross-sectional population-based study.

OBJECTIVES: This study examined the association between anthropometric measurements, lifestyle factors and the prevalence of thyroid nodules among adults in Northeast China. DESIGN: We employed a cross-sectional approach involving a questionnaire survey, which focused on participants' living habits, and a physical examination that included anthropometry and ultrasound imaging. SETTING: The data were procured during multiple trips by medical teams from the first hospital of China Medical University to towns in Northeast China. PARTICIPANTS: Of the 1092 participants, 489 did not have thyroid nodules (mean age: 54.02±11.49 years; 297 females (60.7%)), 99 had single thyroid nodules (mean age: 58.19±10.77 years; 59 females (59.6%)) and 504 had multiple thyroid nodules (mean age: 60.05±10.68 years; 394 females (78.2%)). Inclusion criteria mandated participants be over 20 years old without other medical conditions. We excluded individuals who had undergone surgical resection for thyroid nodules. RESULTS: The prevalence of thyroid nodules was significantly associated with being female (OR 2.569, 95% CI 1.937 to 3.405, p<0.001) and increased age (OR 1.054, 95% CI 1.041 to 1.066, p<0.001). This association was more pronounced in those with multiple thyroid nodules. For males under 60, non-smoking was inversely correlated with the prevalence of multiple thyroid nodules (OR 0.321, 95%CI 0.149 to 0.69, p<0.05). For females under 60, diastolic blood pressure (DBP) was significantly linked with the prevalence of thyroid nodules (OR 0.978, 95% CI 2.614 to 2.705, p<0.05). CONCLUSIONS: Besides gender and age, the prevalence of thyroid nodules in Northeast China correlates with smoking habits and DBP.

The CXCL12/CXCR4/ACKR3 Response Axis in Chronic Neurodegenerative Disorders of the Central Nervous System: Therapeutic Target and Biomarker.

There has been an increase in the incidence of chronic neurodegenerative disorders of the central nervous system, including Alzheimer's and Parkinson's diseases, over the recent years mostly due to the rise in the number of elderly individuals. In addition, various neurodegenerative disorders are related to imbalances in the CXCL12/CXCR4/ACKR3 response axis. Notably, the CXC Chemokine Ligand 12 (CXCL12) is essential for the development of the central nervous system. Moreover, the expression and distribution of CXCL12 and its receptors are associated with the aggravation or alleviation of symptoms of neurodegenerative disorders. Therefore, the current review sought to highlight the specific functions of CXCL12 and its receptors in various neurodegenerative disorders, in order to provide new insights for future research.