Research Articles (Molecular Biology and Human Genetics)
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- ItemBovine tuberculosis in African buffalo (Syncerus caffer): Progression of pathology during infection(PLOS, 2022-11) Lakin, Hilary Ann; Tavalire, Hannah; Sakamoto, Kaori; Buss, Peter; Miller, Michele; Budischak, Sarah A.; Raum, Kristina; Ezenwa, Vanessa O.; Beechler, Brianna; Jolles, AnnaABSTRACT: Background Bovine tuberculosis (BTB) is a zoonotic disease of global importance endemic in African buffalo (Syncerus caffer) in sub-Saharan Africa. Zoonotic tuberculosis is a disease of global importance, accounting for over 12,000 deaths annually. Cattle affected with BTB have been proposed as a model for the study of human tuberculosis, more closely resembling the localization and progression of lesions in controlled studies than murine models. If disease in African buffalo progresses similarly to experimentally infected cattle, they may serve as a model, both for human tuberculosis and cattle BTB, in a natural environment. Methodology/Principal findings We utilized a herd of African buffalo that were captured, fitted with radio collars, and tested for BTB twice annually during a 4-year-cohort study. At the end of the project, BTB positive buffalo were culled, and necropsies performed. Here we describe the pathologic progression of BTB over time in African buffalo, utilizing gross and histological methods. We found that BTB in buffalo follows a pattern of infection like that seen in experimental studies of cattle. BTB localizes to the lymph nodes of the respiratory tract first, beginning with the retropharyngeal and tracheobronchial lymph nodes, gradually increasing in lymph nodes affected over time. At 36 months, rate of spread to additional lymph nodes sharply increases. The lung lesions follow a similar pattern, progressing slowly, then accelerating their progression at 36 months post infection. Lastly, a genetic marker that correlated to risk of M. bovis infection in previous studies was marginally associated with BTB progression. Buffalo with at least one risk allele at this locus tended to progress faster, with more lung necrosis. Conclusions/Significance The progression of disease in the African buffalo mirrors the progression found in experimental cattle models, offering insight into BTB and the interaction with its host in the context of naturally varying environments, host, and pathogen populations.
- ItemDiagnostic accuracy of the FluoroType MTB and MTBDR VER 2.0 assays for the centralized high-throughput detection of Mycobacterium tuberculosis complex DNA and isoniazid and rifampicin resistance(Elsevier Ltd, 2021-09) Dippenaar, Anzaan; Derendinger, Brigitta; Dolby, Tania; Beylis, Natalie; Van Helden, Paul D.; Theron, Grant; Warren, Robin M.; De Vos, MargarethaObjectives To evaluate the accuracy of two new molecular diagnostic tests for the detection of drug-resistant tuberculosis, the FluoroType MTB and MTBDR VER 2.0 assays, in combination with manual and automated DNA extraction methods. Methods Sputa from 360 Xpert Ultra Mycobacterium tuberculosis complex (MTBC)-positive patients and 250 Xpert Ultra MTBC-negative patients were tested. GenoType MTBDRplus served as reference for MTBC and drug resistance detection. Sanger sequencing was used to resolve discrepancies. Results FluoroType MTB VER 2.0 showed similar MTBC sensitivity compared with FluoroType MTBDR VER 2.0 (manual DNA extraction: 91.6% (294/321) versus 89.8% (291/324); p 0.4); automated DNA extraction: 92.1% (305/331) versus 87.7% (291/332); p 0.05)). FluoroType MTBDR VER2.0 showed comparable diagnostic accuracy to FluoroType MTBDR VER1.0 as previously reported for the detection of MTBC and rifampicin and isoniazid resistance. Conclusions The FluoroType MTB and MTBDR VER 2.0 assays together with an automated DNA extraction and PCR set-up platform may improve laboratory operational efficiency for the diagnosis of MTBC and resistance to rifampicin and isoniazid and show promise for the implementation in a centralized molecular drug susceptibility testing model.
- ItemEvolution of bacteria in the human gut in response to changing environments: an invisible player in the game of health(Elsevier B.V., 2021-01) Venkatakrishnan, Aarushi; Holzknecht, Zoie E.; Holzknecht, Rob; Bowles, Dawn E.; Kotzé, Sanet H.; Modliszewski, Jennifer L.; Parker, WilliamSeveral factors in Western society, including widespread use of antibiotics, chronic inflammation, and loss of complex eukaryotic symbionts such as helminths, have a dramatic impact on the ecosystem of the gut, affecting the microbiota hosted there. In addition, reductions in dietary fiber are profoundly impactful on the microbiota, causing extensive destruction of the niche space that supports the normally diverse microbial community in the gut. Abundant evidence now supports the view that, following dramatic alterations in the gut ecosystem, microorganisms undergo rapid change via Darwinian evolution. Such evolutionary change creates functionally distinct bacteria that may potentially have properties of pathogens but yet are difficult to distinguish from their benign predecessors.
- ItemEditorial: FDA-Approved Drug Repositioning for P-Glycoprotein Overexpressing Resistant Cancer(Frontiers Media S.A, 2021-03) Yoon, Sungpil; Wang, Xiaoju; Vongpunsawad, Sompong; Tromp, Gerard; Kuivaniemi, HelenaAnticancer drugs are an essential part of cancer treatment. Cancer cells can, however, develop resistance to these drugs by e.g., P-glycoprotein 1 (P-gp) overexpression or accumulation of mutations in the genes part of growth signaling pathways, apoptotic pathways, or repair system. Intrinsically, metastatic cancers, advanced-stage cancers, or stem cell-like cancers are usually drug-resistant and difficult to treat using current anticancer drugs. The overexpression of P-gp, also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1), is one of the well-known mechanisms of resistance to anticancer drugs. Stem cell-like cancers often overexpress P-gp on their membranes, which results in inefficient treatment using the currently available anticancer drugs (1). It is, therefore, important to investigate novel therapeutic options to treat the P-gp overexpressing drug-resistant cancer cells. Identifying the mechanisms for targeting these cancers can overcome the inefficiencies of current anticancer drugs and lead to better outcomes for patients with P-gp overexpressing cancers.
- ItemReference Intervals for Hematology and Clinical Chemistry for the African Elephant (Loxodonta africana)(Frontiers Media S.A, 2021-03) Steyrer, Christine; Miller, Michele; Hewlett, Jennie; Buss, Peter; Hooijberg, Emma H.The African elephant (Loxodonta africana) is listed as vulnerable, with wild populations threatened by habitat loss and poaching. Clinical pathology is used to detect and monitor disease and injury, however existing reference interval (RI) studies for this species have been performed with outdated analytical methods, small sample sizes or using only managed animals. The aim of this study was to generate hematology and clinical chemistry RIs, using samples from the free-ranging elephant population in the Kruger National Park, South Africa. Hematology RIs were derived from EDTA whole blood samples automatically analyzed (n = 23); manual PCV measured from 48 samples; and differential cell count results (n = 51) were included. Clinical chemistry RIs were generated from the results of automated analyzers on stored serum samples (n = 50). Reference intervals were generated according to American Society for Veterinary Clinical Pathology guidelines with a strict exclusion of outliers. Hematology RIs were: PCV 34–49%, RBC 2.80–3.96 × 1012/L, HGB 116–163 g/L, MCV 112–134 fL, MCH 35.5–45.2 pg, MCHC 314–364 g/L, PLT 182–386 × 109/L, WBC 7.5–15.2 × 109/L, segmented heterophils 1.5–4.0 × 109/L, band heterophils 0.0–0.2 × 109/L, total monocytes 3.6–7.6 × 109/L (means for “regular” were 35.2%, bilobed 8.6%, round 3.9% of total leukocytes), lymphocytes 1.1–5.5 × 109/L, eosinophils 0.0–0.9 × 109/L, basophils 0.0–0.1 × 109/L. Clinical chemistry RIs were: albumin 41–55 g/L, ALP 30–122 U/L, AST 9–34 U/L, calcium 2.56–3.02 mmol/L, CK 85–322 U/L, GGT 7–16 U/L, globulin 30–59 g/L, magnesium 1.15–1.70 mmol/L, phosphorus 1.28–2.31 mmol/L, total protein 77–109 g/L, urea 1.2–4.6 mmol/L. Reference intervals were narrower than those reported in other studies. These RI will be helpful in the future management of injured or diseased elephants in national parks and zoological settings.