Phylogenetic reconstruction of the structure and function of the ancestor of the nuclear receptor protein family reveals how functional diversity evolves by subtle tinkering with an ancestral template.

Background: Drugs that target steroid receptors are notoriously promiscuous, causing an array of off-target side effects. Results: Reversal of the historical mutation H853R in the mineralocorticoid receptor (MR) fully restores agonist activity by mometasone furoate, an MR antagonist. Conclusion: A single residue outside of the ligand-binding pocket toggles agonism versus antagonism response by MR to synthetic ligands. Significance: Ancestral proteins are ideal tools to elucidate the mechanisms of drug selectivity.

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An experiment was planned to explore the possibilities of replacement of concentrate mixture by Hedge lucerne (Desmanthus virgatus) in growing Osmanabadi goats for 90 days. Osmanabadi growing goats (18) of either sex with similar age and body weights (12.77±0.53 kg) were divided into two treatment groups and one control group (T0) with six goats in each group. Concentrate mixture was offered to control group (T0), while T1 and T2 groups received ration in which 50% and 100% concentrate was replaced by Hedge lucerne on dry matter basis. The mean fortnightly dry matter intake (g/d) was significantly higher in control (T0) and T2 than T1. The intake of DCP (g/d) was significantly higher in control and T1 as compared to T2. The per cent digestibility of nutrients namely DM, OM, CP, EE, CF and NFE did not differ significantly amongst the treatment groups. Total gain in body weight (kg) was significantly higher in T1 (2.71±0.13) as compared to T0 (2.58±0.50) and T2 (2.25±0.02). The final body weight of experimental goats were 15.57 kg (T0), 15.18 kg (T1) and 15.61 kg (T2) respectively. The body condition score was significantly higher in T0 and T1 than T2. The total cost of production was significantly higher in T0 (` 1858.86) followed by T1 (` 1810.81) and T2 (` 1725.85). The highest net profit per goat was recorded for T2 (` 2957.15), followed by T0 (` 2812.14) and T1 (` 2743.15) groups. It is concluded that inclusion up to 50% Hedge lucerne to replace concentrate in diet of goats improves growth performance and increases net profit of Osmanabadi goat production.

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