Research Articles (Molecular Biology and Human Genetics)


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    Evolution 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, William
    Several 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.
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    Editorial: 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, Helena
    Anticancer 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.
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    Reference 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.
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    Review of diagnostic tests for detection of mycobacterium bovis infection in South African wildlife
    (Frontiers Media S.A, 2021-01) Bernitz, Netanya; Kerr, Tanya J.; Goosen, Wynand J.; Chileshe, Josephine; Higgitt, Roxanne L.; Roos, Eduard O.; Meiring, Christina; Gumbo, Rachiel; De Waal, Candice; Clarke, Charlene; Smith, Katrin; Goldswain, Samantha; Sylvester, Taschnica T.; Kleynhans, Léanie; Dippenaar, Anzaan; Buss, Peter E.; Cooper, David V.; Lyashchenko, Konstantin P.; Warren, Robin M.; Van Helden, Paul D.; Parsons, Sven D. C.; Miller, Michele A.
    Wildlife tuberculosis is a major economic and conservation concern globally. Bovine tuberculosis (bTB), caused byMycobacteriumbovis (M. bovis), is themost common form of wildlife tuberculosis. In South Africa, to date, M. bovis infection has been detected in 24 mammalian wildlife species. The identification of M. bovis infection in wildlife species is essential to limit the spread and to control the disease in these populations, sympatric wildlife species and neighboring livestock. The detection of M. bovis-infected individuals is challenging as only severely diseased animals show clinical disease manifestations and diagnostic tools to identify infection are limited. The emergence of novel reagents and technologies to identify M. bovis infection in wildlife species are instrumental in improving the diagnosis and control of bTB. This review provides an update on the diagnostic tools to detect M. bovis infection in South African wildlife but may be a useful guide for other wildlife species.
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    Multi-phenotype genome-wide association study of clades causing tuberculosis in a Ghanaian- and South African cohort
    (Elsevier Inc., 2021-04) Müller, Stephanie J.; Haiko, Schurz; Tromp, Gerard; Van der Spuy, Gian D.; Hoal, Eileen G.; Van Helden, Paul D.; Owusu-Dabo, Ellis; Meyer, Christian G.; Muntau, Birgit; Thye, Thorsten; Niemann, Stefan; Warren, Robin M.; Streicher, Elizabeth; Muller, Marlo; Kinnear, Craig
    Despite decades of research and advancements in diagnostics and treatment, tuberculosis remains a major public health concern. New computational methods are needed to interrogate the intersection of host- and bacterial genomes. Paired host genotype datum and infecting bacterial isolate information were analysed for associations using a multinomial logistic regression framework implemented in SNPTest. A cohort of 853 admixed South African participants and a Ghanaian cohort of 1359 participants were included. Two directly genotyped variants, namely rs529920 and rs41472447, were identified in the Ghanaian cohort as being statistically significantly associated with risk for infection with strains of different members of the MTBC. Thus, a multinomial logistic regression using paired host-pathogen data may prove valuable for investigating the complex relationships driving infectious disease.