The algorithm takes the absolute value in order to make the scores symmetric, and then multiplies by –1 to adhere to the substitution matrix convention that more negative scores correspond to more severe substitutions.
In addition, the most severe substitutions, K317A in SFV nsP1, and D310A and W406A in BaMV, reduced the MTAse and GTase activities by ≥90% (Table 1).
The least severe Ala934Val substitution mutation resides on the displaced, disordered loop region that includes the proline-rich region, Leu-954 lies on the MVt extended coil, and the most severe mutation, Arg975Trp, resides on the unique H1' α-helix of metavinculin (Figure 2A).
In contrast, the MRE11A rMS that described from a breast cancer case (p.Thr481Ile), as well as the rMS observed at the same position in a pair of ataxia-telangiectasia-like disease cases (p.Thr481Lys), score as severe C65 substitutions when evaluated with the mammals-only alignment but as likely innocuous C0 substitutions when evaluated with the evolutionarily deep alignment.
A more severe type of base substitution, called a "nonsense" mutation, results in a stop codon in a position where there was not one before, which causes the premature termination of protein synthesis and, more than likely, a complete loss of function in the finished protein.
For more severe humoral immunodeficiency, immunoglobulin substitution is indicated.
The main reasons for drug substitution were severe anaemia and/or treatment for tuberculosis.
The haloacetonitriles showed in utero toxicity, becoming more severe with increasing halogen substitution.
Based on data from the US National Trauma Data Bank (NTDB), Haut et al. demonstrated in a multivariate analysis that extended volume substitution after severe trauma increases mortality.
However, due to a severe slow down of substitution rate in turtles relative to diapsid reptiles [ 43], we can not rule out the possibility that the molecular turtle-archosaur relationship is caused by analytical artifacts.
