The mob mutants in Escherichia coli are pleiotropically defective in all molybdoenzyme activities. They synthesise molybdopterin, the unique core of the molybdenum cofactor, but are unable to attach the GMP moiety to molybdopterin to form molybdopterin guanine dinucleotide, the functional molybdenum cofactor in Escherichia coli. A partially purified preparation termed protein FA (protein factor d'association), is able to restore molybdoenzyme activities to broken cell preparations of mob mutants. A fragment of DNA capable of complementing mob mutants has been isolated from an E. coli genomic library. Strains carrying this DNA in a multicopy plasmid, express 30-fold more protein FA activity than the wild-type bacterium. Protein FA has been purified to homogeneity by a combination of ion-exchange, affinity and gel-filtration chromatography. Protein FA consists of a single polypeptide of molecular mass 22 kDa and is monomeric in solution. N-terminal amino acid sequencing confirmed that protein FA is a product of the first gene at the mob locus. The purified protein FA was required in stoichiometric rather than catalytic amounts in the process that leads to the activation of the precursor of the molybdoenzyme nitrate reductase, which is consistent with the requirement of a further component in the activation.Molybdoenzymes, with the exception of molybdodinitrogenase, contain a molybdenum cofactor which is composed in its simplest form of a unique pterin derivative, molybdopterin, to which the molybdenum is bound [l]. The chlorateresistant mutants of Escherichia coli (recently renamed mo [2]) are pleiotropically defective in all molybdoenzyme activities and are defective in the biosynthesis of active molybdenum cofactor. These mutants carry mutations which map to five distinct regions of the E. coli chromosome: moa, mob, mod, moe and mog. Each of the loci has been cloned and almost all have been sequenced [4-81. The overall functions encoded by most of the loci have been deduced. The moa and moe loci encode proteins which assemble the molybdopterin portion of the cofactor [9, 101. The mod locus encodes the molybdate uptake system of the cell [9, 111. The function of mog is not known [12]. For several years the role of the mob locus in cofactor biosynthesis was unclear since these mutants possessed molybdopterin [13, 141. However, recently it has been demonstrated that in E. coli the active form of the cofactor is molybdopterin guanine dinucleotide (MGD), a covalent complex of molybdopterin with guanosine monophosphate. Mutants defective at mob are unable to attach GMP to molybdopterin, suggesting that the products of the mob locus are responsible for this late step in molybdenum cofactor biosynthesis [15].

Recent publications on the probable role of heparin-binding protein (HBP) as a biomarker in sepsis prompted us to investigate its diagnostic and prognostic performance in severe COVID-19. HBP and IL-6 were measured by immunoassays at admission and on day 7 in 178 patients with pneumonia by SARS-CoV-2. Patients were classified into non-sepsis and sepsis as per the Sepsis-3 definitions and were followed up for the development of severe respiratory failure (SRF) and for outcome. Results were confirmed by multivariate analyses. HBP was significantly higher in patients classified as having sepsis and was negatively associated with the oxygenation ratio and positively associated with creatinine and lactate. Logistic regression analysis evidenced admission HBP more than 18 ng/ml and IL-6 more than 30 pg/ml as independent risk factors for the development of SRP. Their integration prognosticated SRF with respective sensitivity, specificity, positive predictive value, and negative predictive 59.1%, 96.3%, 83.9%, and 87.8%. Cox regression analysis evidenced admission HBP more than 35 ng/ml and IL-6 more than 30 pg/ml as independent risk factors for 28-day mortality. Their integration prognosticated 28-day mortality with respective sensitivity, specificity, positive predictive value, and negative predictive value 69.2%, 92.7%, 42.9%, and 97.5%. HBP remained unchanged over-time course. A prediction score of the disposition of patients with COVID-19 is proposed taking into consideration admission levels of IL-6 and HBP. Using different cut-offs, the score may predict the likelihood for SRF and for 28-day outcome.

Background: The validation of new biomarkers for the diagnosis and risk stratification of patients with sepsis at an early point is essential for successful treatment. Recent publications prompted us to investigate of heparin binding protein (HBP) for the emergency department (ED) admissions. Materials and Methods: In this multicenter, cross-sectional study, HBP and procalcitonin (PCT) were measured within the first hour upon admission to the ED in plasma samples of 371 patients with signs of infection. Patients were classified into non-sepsis and sepsis by the Sepsis-3 definitions and were followed up for outcome. Results: HBP was significantly higher in patients with sepsis and was positively correlated to PCT and C-reactive protein, absolute neutrophil and monocyte counts, creatinine, bilirubin and lactate. Sensitivity, specificity, positive predictive value, and negative predictive value of HBP more than 19.8 ng/mL for the diagnosis of sepsis was 66.3%, 44.9%, 49.3%, and 62.2%, respectively; and for prediction of early death was 100%, 41.0%, 4.5%, and 100%, respectively. Single HBP and PCT could not predict 28-day mortality; this was performed with sensitivity, specificity, positive predictive value, and negative predictive value 44.8%, 81.8%, 17.3%, and 94.6% when used in combination. Conclusion: Admission HBP can be used as a tool for the early diagnosis of sepsis and for the risk of early death in the ED.

Purpose Recent publications on the probable role of heparin-binding protein (HBP) as a biomarker in sepsis prompted us to investigate its diagnostic and prognostic performance in severe COVID-19Methods HBP and IL-6 were measured by immunoassays at admission and on day 7 in 178 patients with pneumonia by SARS-CoV-2. Patients were classified into non-sepsis and sepsis as per the Sepsis-3 definitions and were followed-up for the development of severe respiratory failure (SRF) and for outcome. Results were confirmed by multivariate analyses.Results HBP was significantly higher in patients classified as having sepsis and was negatively associated with the oxygenation ratio and positively associated with creatinine and lactate. Logistic regression analysis evidenced admission HBP more than 18 ng/ml and IL-6 more than 30 pg/ml as independent risk factors for the development of SRP. Their integration prognosticated SRF with respective sensitivity, specificity, positive predictive value and negative predictive 59.1%, 96.3%, 83.9% and 87.8%. Cox regression analysis evidenced admission HBP more than 35 ng/ml and IL-6 more than 30 pg/ml as independent risk factors for 28-day mortality. Their integration prognosticated 28-day mortality with respective sensitivity, specificity, positive predictive value and negative predictive 69.2%, 92.7%, 42.9% and 97.5%. HBP remained unchanged over-time course. Conclusion A prediction score of the disposition of patients with COVID-19 is proposed taking into consideration admission levels of IL-6 and HBP. Using different cut-offs the score may predict the likelihood for SRF and for 28-day outcome.

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