Genetic studies have indicated that the facB gene of Aspergillus nidulans is a major regulatory gene involved in acetamide and acetate utilisation. Sequencing of the facB gene revealed that it encodes a protein that contains an N-terminal GAL4-like Zn(II)2Cys6 (or C6 zinc) binuclear cluster for DNA binding, leucine zipper-like heptad repeat motifs and central and C-terminal acidic alpha-helical regions, consistent with a function as a DNA-binding transcriptional activator. The Zn(II)2Cys6 cluster shows strong similarity with those of the Saccharomyces cerevisiae carbon metabolism regulatory proteins CAT8 and SIP4. A significant level of similarity with CAT8 is found throughout the length of the protein, suggesting at least partial functional homology. The facB genes of Aspergillus oryzae and Aspergillus niger were also sequenced and found to be highly conserved. Deletion of the facB gene confirmed that it is required for growth on acetate as a sole carbon source. Functional dissection using deletion and fusion constructs and in vitro mutagenesis indicated that the Zn(II)2Cys6 cluster and the C-terminal end of the protein are required for function.
Background Autoimmune rheumatologic disease associated interstitial lung diseases (ARD-ILD) are rare conditions and the association between ARDs and respiratory symptoms often goes unrecognised by ARD patients and general practitioners (GPs). The diagnostic trajectory from the first respiratory symptoms to an ARD-ILD diagnosis is often delayed and may increase the burden of symptoms and allow further disease progression.The aim of this study was to 1) characterise the diagnostic trajectories of ARD-ILD patients and to 2) identify barriers for obtaining a timely ILD diagnosis based on the experiences and perceptions of both patients and healthcare professionals. Method Semi-structured qualitative interviews were conducted with Danish ARD-ILD patients, rheumatologists, pulmonologists and ILD nurses. Results Sixteen patients, six rheumatologists, three ILD nurses and three pulmonologists participated. Five characteristics of diagnostic trajectories were identified in the patient interviews: 1) early referral to lung specialists; 2) early delay; 3) delay or shortcut depending on specific circumstances; 4) parallel diagnostic trajectories connected late in the process; 5) early identification of lung involvement without proper interpretation. With the exception of early referral to lung specialists, all of the diagnostic trajectory characteristics identified led to delayed diagnosis. Delayed diagnostic trajectories resulted in patients experiencing increased uncertainty. Inconsistent disease terminology, insufficient knowledge and lack of awareness of ARD-ILD among central healthcare professionals and delayed referral to ILD specialists were main contributors to the diagnostic delay identified by the informants. Conclusion Five characteristics of the diagnostic trajectories were identified, four of which led to diagnostic delay of ARD-ILD. Improved diagnostic trajectories can shorten the diagnostic trajectory and increase early access to appropriate specialist medical care. Improved awareness and expertise in ARD-ILD across different medical specialties, especially among GPs, may contribute to more efficient and timely diagnostic trajectories and improved patient experiences.
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