Reflections on IDEAL: What we have learnt from a unique calf cohort study

The year 2020 marks a decade since the final visit was made in the ‘Infectious Diseases of East African Livestock’ (IDEAL) project. However, data generation from samples obtained during this ambitious longitudinal study still continues. As the project launches its extensive open-access database and biobank to the scientific community, we reflect on the challenges overcome, the knowledge gained, and the advantages of such a project. We discuss the legacy of the IDEAL project and how it continues to generate evidence since being adopted by the Centre for Tropical Livestock Genetics and Health (CTLGH). We also examine the impact of the IDEAL project, from the authors perspective, for each of the stakeholders (the animal, the farmer, the consumer, the policy maker, the funding body, and the researcher and their institution) involved in the project and provide recommendations for future researchers who are interested in running longitudinal field studies.The Bill & Melinda Gates Foundation, the UK Government’s Department for International Development and the International Livestock Research Institute.http://www.elsevier.com/locate/prevetmedam2021Veterinary Tropical Disease

Bluetongue and Epizootic Haemorrhagic Disease virus in local breeds of cattle in Kenya

AbstractThe presence of bluetongue virus (BTV) and Epizootic Haemorrhagic Disease virus (EHDV) in indigenous calves in western Kenya was investigated. Serum was analysed for BTV and EHDV antibodies. The population seroprevalences for BTV and EHDV for calves at 51weeks of age were estimated to be 0.942 (95% CI 0.902–0.970) and 0.637 (95% CI 0.562–0.710), respectively, indicating high levels of circulating BTV and EHDV. The odds ratio of being positive for BTV if EHDV positive was estimated to be 2.57 (95% CI 1.37–4.76). When 99 calves were tested for BTV and EHDV RNA by real-time RT-PCR, 88.9% and 63.6% were positive, respectively. Comparison of the serology and real-time RT-PCR results revealed an unexpectedly large number of calves that were negative by serology but positive by real-time RT-PCR for EHDV. Eight samples positive for BTV RNA were serotyped using 24 serotype-specific real-time RT-PCR assays. Nine BTV serotypes were detected, indicating that the cattle were infected with a heterogeneous population of BTVs. The results show that BTV and EHDV are highly prevalent, with cattle being infected from an early age

Severe Ankyrin-R deficiency results in impaired surface retention and lysosomal degradation of RhAG in human erythroblasts

Ankyrin-R provides a key link between band 3 and the spectrin cytoskeleton that helps to maintain the highly specialized erythrocyte biconcave shape. Ankyrin deficiency results in fragile spherocytic erythrocytes with reduced band 3 and protein 4.2 expression. We use in vitro differentiation of erythroblasts transduced with shRNAs targeting ANK1 to generate erythroblasts and reticulocytes with a novel ankyrin-R ʼnear null’ human phenotype with less than 5% of normal ankyrin expression. Using this model, we demonstrate that absence of ankyrin negatively impacts the reticulocyte expression of a variety of proteins, including band 3, glycophorin A, spectrin, adducin and, more strikingly, protein 4.2, CD44, CD47 and Rh/RhAG. Loss of band 3, which fails to form tetrameric complexes in the absence of ankyrin, alongside GPA, occurs due to reduced retention within the reticulocyte membrane during erythroblast enucleation. However, loss of RhAG is temporally and mechanistically distinct, occurring predominantly as a result of instability at the plasma membrane and lysosomal degradation prior to enucleation. Loss of Rh/RhAG was identified as common to erythrocytes with naturally occurring ankyrin deficiency and demonstrated to occur prior to enucleation in cultures of erythroblasts from a hereditary spherocytosis patient with severe ankyrin deficiency but not in those exhibiting milder reductions in expression. The identification of prominently reduced surface expression of Rh/RhAG in combination with direct evaluation of ankyrin expression using flow cytometry provides an efficient and rapid approach for the categorization of hereditary spherocytosis arising from ankyrin deficiency