Enhancing individual animal resilience to environmental disturbances to address low productivity in dairy cattle performing in sub-Saharan Africa

The current review examines potential solutions to enhance the sustainability and productivity of the dairy sector in sub-Saharan Africa (SSA) with an emphasis on breeding for resilience. Additionally, the paper explores various indicators for measuring resilience and provides insights into the data that can be utilized to quantify resilience in SSA’s dairy production systems. Dairy production contributes significantly to food and nutritional security and employment in SSA. However, besides the general lack of enabling policy and institutional environments, production is negatively affected by environmental challenges such as high temperatures and heat stress, diseases and parasites, unreliable rainfall patterns, shortages of feeds and forages and undue preference for taurine cattle breeds regardless of their poor adaptability to prevailing local conditions. Fostering the resilience capacity of dairy animals is imperative to combat climate-related adversities and maintain productivity. This can only be achieved if reliable and practical methods for quantifying and analyzing resilience in SSA are described and undertaken. This study has reviewed variance of deviations, root mean square of deviations, autocorrelation of deviations, skewness of deviations, slope of the reaction norm and its absolute value as possible indicators of resilience in SSA. While previous research has reported genetic variation and favorable correlations of these indicators with health, fitness, and fertility traits, their potential in SSA environments requires further investigation. Besides, labor- and cost-effective phenotypic data collection is essential for characterization of resilience using these indicators. Through this study, we propose frequently collected data on milk production traits, body fat-related traits, and activity patterns as suitable in the sub-Saharan Africa context. The African Asian Dairy Genetic Gains Project by the International Livestock Research Institute (ILRI) offers a valuable opportunity to collate data from diverse dairy systems in SSA for testing the potential of these indicators. Insights from this study are helpful in improving resilience of dairy animals in SSA, which would contribute to poverty alleviation, animal welfare improvement, and better preparedness in lieu of climate change in SSA.</p

The translocation mechanism of P-glycoprotein

AbstractMultidrug transporters are involved in mediating the failure of chemotherapy in treating several serious diseases. The archetypal multidrug transporter P-glycoprotein (P-gp) confers resistance to a large number of chemically and functionally unrelated anti-cancer drugs by mediating efflux from cancer cells. The ability to efflux such a large number of drugs remains a biological enigma and the lack of mechanistic understanding of the translocation pathway used by P-gp prevents rational design of compounds to inhibit its function. The translocation pathway is critically dependent on ATP hydrolysis and drug interaction with P-gp is possible at one of a multitude of allosterically linked binding sites. However, aspects such as coupling stoichiometry, molecular properties of binding sites and the nature of conformational changes remain unresolved or the centre of considerable controversy. The present review attempts to utilise the available data to generate a detailed sequence of events in the translocation pathway for this dexterous protein

The translocation mechanism of P-glycoprotein

AbstractMultidrug transporters are involved in mediating the failure of chemotherapy in treating several serious diseases. The archetypal multidrug transporter P-glycoprotein (P-gp) confers resistance to a large number of chemically and functionally unrelated anti-cancer drugs by mediating efflux from cancer cells. The ability to efflux such a large number of drugs remains a biological enigma and the lack of mechanistic understanding of the translocation pathway used by P-gp prevents rational design of compounds to inhibit its function. The translocation pathway is critically dependent on ATP hydrolysis and drug interaction with P-gp is possible at one of a multitude of allosterically linked binding sites. However, aspects such as coupling stoichiometry, molecular properties of binding sites and the nature of conformational changes remain unresolved or the centre of considerable controversy. The present review attempts to utilise the available data to generate a detailed sequence of events in the translocation pathway for this dexterous protein