Suicide inhibition of alpha-oxamine synthases:structures of the covalent adducts of 8-amino-7-oxononanoate synthase with trifluoroalanine

The suicide inhibition of the α-oxamine synthases by the substrate analog, L-trifluoroalanine was investigated. The inhibition resulted in the formation of a complex with loss of all three fluorine atoms. Decarboxylation and loss of fluoride occurred immediately after aldimine formation. The inherent flexibility could allow the difluorinated intermediate complex to adopt a suitable conformation. Decarboxylation in the normal mechanism occurs after formation of the ketoacid intermediate.link_to_subscribed_fulltex

Plasma biomarkers for Alzheimer’s disease: a field-test in a memory clinic

BACKGROUND: The key Alzheimer's disease (AD) biomarkers are traditionally measured with techniques/exams that are either expensive (amyloid-positron emission tomography (PET) and tau-PET), invasive (cerebrospinal fluid Aβ42 and p-tau181), or poorly specific (atrophy on MRI and hypometabolism on fluorodeoxyglucose-PET). Recently developed plasma biomarkers could significantly enhance the efficiency of the diagnostic pathway in memory clinics and improve patient care. This study aimed to: (1) confirm the correlations between plasma and traditional AD biomarkers, (2) assess the diagnostic accuracy of plasma biomarkers as compared with traditional biomarkers, and (3) estimate the proportion of traditional exams potentially saved thanks to the use of plasma biomarkers. METHODS: Participants were 200 patients with plasma biomarkers and at least one traditional biomarker collected within 12 months. RESULTS: Overall, plasma biomarkers significantly correlated with biomarkers assessed through traditional techniques: up to r=0.50 (p<0.001) among amyloid, r=0.43 (p=0.002) among tau, and r=-0.23 (p=0.001) among neurodegeneration biomarkers. Moreover, plasma biomarkers showed high accuracy in discriminating the biomarker status (normal or abnormal) determined by using traditional biomarkers: up to area under the curve (AUC)=0.87 for amyloid, AUC=0.82 for tau, and AUC=0.63 for neurodegeneration status. The use of plasma as a gateway to traditional biomarkers using cohort-specific thresholds (with 95% sensitivity and 95% specificity) could save up to 49% of amyloid, 38% of tau, and 16% of neurodegeneration biomarkers. CONCLUSION: The implementation of plasma biomarkers could save a remarkable proportion of more expensive traditional exams, making the diagnostic workup more cost-effective and improving patient care

Application of the Mason−Schamp Equation and Ion Mobility Mass Spectrometry To Identify Structurally Related Compounds in Crude Oil

The various components of crude oil were structurally resolved using an atmospheric-pressure solids analysis probe (ASAP) coupled with ion mobility mass spectrometry (IM-MS). An ASAP source was used to broadly fractionate compounds according to their boiling points, thereby simplifying the resulting mass spectra for easier data interpretation. The m/z−mobility plots obtained by IM-MS analysis of crude oil could be used to find the structural relationship between crude oil molecules. That was demonstrated using ion mobility mass spectra from a homologous series of compounds, differing only by the number of alkyl units, found in crude oil. The peaks from this series were linearly aligned in the plot, suggesting a continuous increase of the collisional cross section with an increase of mass values and hence the absence of significant structural differences within the series. In contrast, peaks in a homologous series differing only in the number of pendant hydrogen atoms were not linearly aligned, suggesting a discontinuous increase of the collisional cross section with an increase of mass values and hence significant structural differences due to the addition or removal of hydrogen. Cases in which a slope change was observed at three- or four-peak intervals may be related to the addition of an aromatic ring to existing structures. Overall, ion mobility mass spectrometry demonstrates a useful tool that can be used to elucidate structural relationships between molecules comprising crude oil

Plasma biomarkers for Alzheimer's disease: a field-test in a memory clinic

Background: The key Alzheimer's disease (AD) biomarkers are traditionally measured with techniques/exams that are either expensive (amyloid-positron emission tomography (PET) and tau-PET), invasive (cerebrospinal fluid Aβ42 and p-tau181), or poorly specific (atrophy on MRI and hypometabolism on fluorodeoxyglucose-PET). Recently developed plasma biomarkers could significantly enhance the efficiency of the diagnostic pathway in memory clinics and improve patient care. This study aimed to: (1) confirm the correlations between plasma and traditional AD biomarkers, (2) assess the diagnostic accuracy of plasma biomarkers as compared with traditional biomarkers, and (3) estimate the proportion of traditional exams potentially saved thanks to the use of plasma biomarkers. Methods: Participants were 200 patients with plasma biomarkers and at least one traditional biomarker collected within 12 months. Results: Overall, plasma biomarkers significantly correlated with biomarkers assessed through traditional techniques: up to r=0.50 (p&lt;0.001) among amyloid, r=0.43 (p=0.002) among tau, and r=-0.23 (p=0.001) among neurodegeneration biomarkers. Moreover, plasma biomarkers showed high accuracy in discriminating the biomarker status (normal or abnormal) determined by using traditional biomarkers: up to area under the curve (AUC)=0.87 for amyloid, AUC=0.82 for tau, and AUC=0.63 for neurodegeneration status. The use of plasma as a gateway to traditional biomarkers using cohort-specific thresholds (with 95% sensitivity and 95% specificity) could save up to 49% of amyloid, 38% of tau, and 16% of neurodegeneration biomarkers. Conclusion: The implementation of plasma biomarkers could save a remarkable proportion of more expensive traditional exams, making the diagnostic workup more cost-effective and improving patient care.</p

Purification and characterisation of the BIOH protein from the biotin biosynthetic pathway

AbstractConversion of pimeloyl-coenzyme A (CoA) to biotin in Escherichia coli requires at least four enzymes encoded by genes in the bio operon. One gene, bioH, which is not present in the bioABFCD operon, is required for the synthesis of pimeloyl-CoA but its exact role in formation of this intermediate is unknown. To investigate this further, we have overexpressed and purified the bioH gene products from both E. coli (BIOH EC) and Neisseria meningitis (BIOH NM) in E. coli. When purified BIOH was incubated with excess CoA and analysed by electrospray mass spectrometry a species of mass corresponding to a BIOH:CoA complex was observed. Mutation of a conserved serine residue to alanine (BIOH EC S82A) did not prevent CoA binding. This is the first report of the purification of BIOH and the observation of a small molecule bound to the protein provides clues to its role in pimeloyl-CoA synthesis

Research priorities to strengthen environmental cleaning in healthcare facilities: the CLEAN Group Consensus

Environmental cleaning is essential to patient and health worker safety, yet it is a substantially neglected area in terms of knowledge, practice, and capacity-building, especially in resource-limited settings. Public health advocacy, research and investment are urgently needed to develop and implement cost-effective interventions to improve environmental cleanliness and, thus, overall healthcare quality and safety. We outline here the CLEAN Group Consensus exercise yielding twelve urgent research questions, grouped into four thematic areas: standards, system strengthening, behaviour change, and innovation