Mycobacterial Esx-3 Requires Multiple Components for Iron Acquisition

ABSTRACT The type VII secretion systems are conserved across mycobacterial species and in many Gram-positive bacteria. While the well-characterized Esx-1 pathway is required for the virulence of pathogenic mycobacteria and conjugation in the model organism Mycobacterium smegmatis, Esx-3 contributes to mycobactin-mediated iron acquisition in these bacteria. Here we show that several Esx-3 components are individually required for function under low-iron conditions but that at least one, the membrane-bound protease MycP3 of M. smegmatis, is partially expendable. All of the esx-3 mutants tested, including the ΔmycP3ms mutant, failed to export the native Esx-3 substrates EsxHms and EsxGms to quantifiable levels, as determined by targeted mass spectrometry. Although we were able to restore low-iron growth to the esx-3 mutants by genetic complementation, we found a wide range of complementation levels for protein export. Indeed, minute quantities of extracellular EsxHms and EsxGms were sufficient for iron acquisition under our experimental conditions. The apparent separation of Esx-3 function in iron acquisition from robust EsxGms and EsxHms secretion in the ΔmycP3ms mutant and in some of the complemented esx-3 mutants compels reexamination of the structure-function relationships for type VII secretion systems

A Stakeholder-Informed Approach to the Identification of Criteria for the Prioritization of Zoonoses in Canada

Background: Zoonotic diseases account for over 60 % of all communicable diseases causing illness in humans and 75 % of recently emerging infectious diseases. As limited resources are available for the control and prevention of zoonotic diseases, it is necessary to prioritize diseases in order to direct resources into those with the greatest needs. The selection of criteria for prioritization has traditionally been on the basis of expert opinion; however, details of the methods used to identify criteria from expert opinion often are not published and a full range of criteria may not be captured by expert opinion. Methodology/Principal Findings: This study used six focus groups to identify criteria for the prioritization of zoonotic diseases in Canada. Focus groups included people from the public, animal health professionals and human health professionals. A total of 59 criteria were identified for prioritizing zoonotic diseases. Human-related criteria accounted for the highest proportion of criteria identified (55%), followed by animal-related criteria (26%) then pathogen/disease-related criteria (19%). Similarities and differences were observed in the identification and scoring of criteria for disease prioritization between groups; the public groups were strongly influenced by the individual-level of disease burden, the responsibility of the scientific community in disease prioritization and the experiences of recent events while the professional groups were influenced by the societal- and population-level of disease burden and political and public pressure

Settler state apologies and the elusiveness of forgiveness : The purification ritual that does not purify

Peer reviewedPostprin

Comparison of Proteomic and Transcriptomic Profiles in the Bronchial Airway Epithelium of Current and Never Smokers

Although prior studies have demonstrated a smoking-induced field of molecular injury throughout the lung and airway, the impact of smoking on the airway epithelial proteome and its relationship to smoking-related changes in the airway transcriptome are unclear.Airway epithelial cells were obtained from never (n = 5) and current (n = 5) smokers by brushing the mainstem bronchus. Proteins were separated by one dimensional polyacrylamide gel electrophoresis (1D-PAGE). After in-gel digestion, tryptic peptides were processed via liquid chromatography/ tandem mass spectrometry (LC-MS/MS) and proteins identified. RNA from the same samples was hybridized to HG-U133A microarrays. Protein detection was compared to RNA expression in the current study and a previously published airway dataset. The functional properties of many of the 197 proteins detected in a majority of never smokers were similar to those observed in the never smoker airway transcriptome. LC-MS/MS identified 23 proteins that differed between never and current smokers. Western blotting confirmed the smoking-related changes of PLUNC, P4HB1, and uteroglobin protein levels. Many of the proteins differentially detected between never and current smokers were also altered at the level of gene expression in this cohort and the prior airway transcriptome study. There was a strong association between protein detection and expression of its corresponding transcript within the same sample, with 86% of the proteins detected by LC-MS/MS having a detectable corresponding probeset by microarray in the same sample. Forty-one proteins identified by LC-MS/MS lacked detectable expression of a corresponding transcript and were detected in <or=5% of airway samples from a previously published dataset.1D-PAGE coupled with LC-MS/MS effectively profiled the airway epithelium proteome and identified proteins expressed at different levels as a result of cigarette smoke exposure. While there was a strong correlation between protein and transcript detection within the same sample, we also identified proteins whose corresponding transcripts were not detected by microarray. This noninvasive approach to proteomic profiling of airway epithelium may provide additional insights into the field of injury induced by tobacco exposure

Can mHealth Technology Help Mitigate the Effects of the COVID-19 Pandemic?

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GENETIC ANALYSIS OF 5 α REDUCTASE TYPE II ENZYME IN RELATION TO OXIDATIVE STRESS IN CASES OF ANDROGENETIC ALOPECIA IN A SAMPLE OF EGYPTIAN POPULATION

Objective: To study the genetic polymorphism of 5-α reductase type II enzyme in relation to oxidative stress in cases of androgenetic alopecia (AGA) in a sample of Egyptian population. Materials and Methods: This study was conducted on 45 patients with different grades of AGA,and 45 healthy subjects as control group. Laboratory tests included DNA extraction from blood, amplification of the 5-α reductase type II by PCR and V89L mutation analysis by restriction endonuclease enzyme Rsa?, and estimation of the levels of plasma catalase and erythrocyte lysate superoxide dismutase (SOD) enzymes by colorimetric methods. Results: The studied subjects carrying the homozygote( LL) and the heterozygote (VL) genotypes were of no risk of developing AGA.(OR=0). Regarding the leucine allele, the studied subjects carrying the (L) allele were at about 3.7 higher risk of AGA .(OR=3.692), and the results were statistically significant (p<0.001). There was significant increase in the level of SOD and catalase in patients than in control group(p=0.005),and (p<0.001) respectively,plasma catalase is significantly higher in patients with LLvariant than inVL variant (p=0.020). Asignificant relations was found between the severity of the disease and age and family history (p=0.037), and (0.036) respectively, there was no significant correlation between the level of catalase enzyme and SOD in one hand and the severity of the disease among patients. Conclusions: There is a possible association between AGA and V89L genetic polymorphism of 5-alpha reductase type II enzyme, patients carrying the mutant leucine (L) allele have a risk for developing AGA. Also there is possible association between AGA with oxidative stress.