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Hurt, D.

Publications and source records attributed to Hurt, D..

3 recordsLinked to original sources

Current challenges in microbiome metadata collection

While the biomedical community has embraced data sharing (e.g. results, raw data) and supported establishment of large research consortia (e.g. the Human Microbiome Project) aimed to standardize the quality of important sets of microbiome sequencing data, the reusability of most microbiome data is still limited by the quality of its associated metadata. To ensure that microbiome data is indeed FAIR (Findable, Accessible, Interoperable, and Reusable), it is necessary to consider tools and approaches that make it easier to provide high-quality metadata that is fit for purpose moving forward. Such tools and approaches could be informed by current efforts to harmonize and improve the quality of extant microbiome metadata.

scientific communication and education↗

Metabolic fate of human immunoactive sterols in Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) infection is among top ten causes of death worldwide, and the number of drug-resistant strains is increasing. The direct interception of human immune signaling molecules by Mtb remains elusive, limiting drug discovery. Oxysterols and secosteroids regulate both innate and adaptive immune responses. Here we report a functional, structural, and bioinformatics study of Mtb enzymes initiating cholesterol catabolism and demonstrated their interrelation with human immunity. We show that these enzymes metabolize human immune oxysterol messengers. Rv2266, the most potent among them, can also metabolize vitamin D3 (VD3) derivatives. High-resolution structures show common patterns of sterols binding and reveal a site for oxidative attack during catalysis. Finally, we designed a compound that binds and inhibits three studied proteins. The compound shows activity against Mtb H37Rv residing in macrophages. Our findings contribute to molecular understanding of suppression of immunity and suggest that Mtb has its own transformation system resembling the human phase I drug-metabolizing system.Competing Interest StatementA.Gi. and E.S. are employees of MT-Medicals LLC. The other authors declare no competing interests.View Full Text

biochemistry↗

Prediction of multiple drug resistant pulmonary tuberculosis against drug sensitive pulmonary tuberculosis by CT nodular consolidation sign

Multidrug-resistant tuberculosis (mdrtb) refers to TB infection resistant to at least two most powerful anti-TB drugs, isoniazid and rifampincin. It has been estimated that globally 3.5% (which can be much higher in some regions) of newly diagnosed TB patients, and 20.5% of previously treated patients had mdrtb. Extensively drug-resistant TB (xdrtb) has resistance to rifampin and isoniazid, as well as to any member of the quinolone family and at least one of the second line injectable drugs: kanamycin, amikacin and capreomycin. xdrtb accounts for 4-20% of mdrtb. Early detection and targeted treatment are priorities for mdrtb/xdrtb control. The suspicion of mdr/xdr -pulmonary TB (mdrptb or xdrptb) by chest imaging shall suggest intensive diagnostic testing for mdrptb/xdrptb. We hypothesize that multiple nodular consolidation (NC) may serve one of the differentiators for separating dsptb vs mdrptb/xdrptb cases. For this study, mdrptb cases (n=310) and XDR-PTB cases ([xcap]=I58) were from the NIAID TB Portals Program (TBPP) . Drug sensitive pulmonary TB (dsptb) cases were from the TBPP collection (n=112) as well as the Shenzhen Center for Chronic Disease Control (n=111), Shenzhen, China, and we excluded patients with HIV(+) status. Our study shows NC, particularly multiple NCs, is more common in mdrptb than in dsptb, and more common in xdrptb than in mdrptb. For example, 2.24% of dsptb patients, 13.23% of mdrptb patients, and 20.89% of xdrptb patients, respectively, have NCs with diameter >= 10mm equal or more than 2 in number.

pathology↗