The restricted sharing of alleles in different populations of cynomolgus macaques, and moreover the recombination of similar alleles into other haplotypes in these populations, suggests that the diversity within the Mafa-B region has been the result of recombination and reshuffling of B-like loci during evolution. The cohort under study has been pedigreed for up to 8 generations, however, the haplotypes listed are observed in maximal five generations of related animals. The finding that within this cohort only one crossing between Mafa-A and Mafa-B is observed may be due to this relatively small number of generations. The fact that each cohort of animals has its own set of alleles and haplotypes necessitates investigation of the MHC for each cohort under study. Only within a breeding colony are the haplotypes more or less stable and predictable, and once the haplotypes are inventoried, robust MHC typing based on microsatellite analyses may be performed. Recombinations can be traced by using microsatellites spanning the whole MHC region. Fig. 1 . The phylogenetic tree shows that cynomolgus and rhesus sequences are fully intertwined, and each clade contains alleles of both species. In total, 17 sets of alleles were observed that are identical for all exons (Table 3) , and this number is in the same order of magnitude as the shared alleles among different populations of cynomolgus macaques. For instance, 25 Mafa-B alleles were described in the cohort Filipino cynomolgus macaques, of which three alleles were shared with animals of Indonesian origin (Campbell et al. 2009 ). Next to these shared alleles are several that differ by only one or two basepairs. Identity at the predicted amino-acid level for these alleles was not investigated. The sharing of haplotypes between cynomolgus and rhesus macaques was also investigated. Only one combination of three Mafa-B sequences was present in the rhesus macaque, and interestingly this was the B*0110102/ B*01201/B*05001 combination mentioned above. Moreover, this Mamu-B*03601/2/B*04501/2/B*03701 haplotype is one of four combinations that is shared by Indian and Chinese rhesus macaques, apart from a few basepair differences. The cynomolgus version differs by three basepairs in Mafa-B*01201 from the Indian rhesus macaque haplotype. The presence of the haplotype in different cohorts of rhesus monkeys and in the Indonesian/Mauritian cynomolgus macaques suggests that its ancestor was already present before the separation of both species. The stability of the haplotype during macaque evolution may have been caused by a significant advantage in the combat of intercellular pathogens. It is also possible that the sharing of the haplotype results from hybridisation. Molecular studies have revealed that introgression from rhesus macaques to cynomolgus monkeys has occured into the Indo-Chinese peninsula ). Fig. 1 Phylogenetic analyses of Mafa-B alleles detected in this study and Mamu-B alleles in known haplotypes of Indian and Chinese rhesus monkeys. The analyses are based on the exon 2, 3 and 4 sequences. Alleles that seem identical in this three may have basepair differences in other exons. The two species of macaques are indicated by different colors. Mafa/Mamu-B alleles of the one shared haplotype are depicted in green. The extension of allele-names with mi means that these are minors; alleles with relatively low transcription Similarities in the genetics of the macaque MHC class I regions are at this stage unfortunately not reflected in the nomenclature for Mhc-B alleles. The recent renaming of Mhc-A alleles has led to a nomenclature in which the distinct A loci and lineage numbers are compatible for all macaque species. For the Mhc-B region in macaques, however, it is not yet possible to assign the transcribed alleles to distinct B loci on the chromosome (e.g. Mamu-B1, -B2, -B3 etc.). However, it would be useful to adjust the lineage numbers (first three ciphers after the asterisk) so that the same numbers refer to similar sequences in different macaque species. Should more information become available in the near future on the number and order of B genes/loci on the macaque haplotypes, the allele designations may then easily be extended by a cipher following the B, without affecting the lineage numbers. In Vitro Viability and Cytotoxicity Testing and Same-Well Multi-Parametric Combinations for High Throughput Screening In vitro cytotoxicity testing has become an integral aspect of drug discovery because it is a convenient, costeffective, and predictive means of characterizing the toxic potential of new chemical entities. The early and routine implementation of this testing is testament to its prognostic importance for humans. Although a plethora of assay chemistries and methods exist for 96-well formats, few are practical and sufficiently sensitive enough for application in high throughput screening (HTS). Here we briefly describe a handful of the currently most robust and validated HTS assays for accurate and efficient assessment of cytotoxic risk. We also provide guidance for successful HTS implementation and discuss unique merits and detractions inherent in each method. Lastly, we discuss the advantages of combining specific HTS compatible assays into multi-parametric, same-well formats. A significant advance in the field of early medicine was Paracelsus' recognition that all compounds have the capacity to be poisonous depending upon dosage [1] . This observation makes toxicity testing a necessary and critical industry practice to identify and define safety thresholds for all new potential chemotherapeutics. The advent of in vitro cytotoxicity testing has greatly streamlined this process and is now considered to be a nearly compulsory activity starting at target validation and continuing through medicinal modification.