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Biology subjects

Wiseman, R.

Publications and source records attributed to Wiseman, R..

3 recordsLinked to original sources

Local population structure in Cambridgeshire during the Roman occupation

The Roman period saw the empire expand across Europe and the Mediterranean, including much of what is today the United Kingdom. While there is written evidence of high mobility into and out of Britain for administrators, traders and the military, the impact of imperialism on local population structure is invisible in the textual record. The extent of genetic change that occurred in Britain before the Early Medieval Period and how closely linked by genetic kinship the local populations were, remains underexplored. Here, using genome-wide data from 52 ancient individuals from Cambridgeshire, we show low levels of genetic ancestry differentiation between Romano-British sites and lower levels of runs of homozygosity over 4 centimorgans (cM than in the Bronze Age and Neolithic. We find fourteen cases of genetic relatedness within and one between sites without evidence of patrilineal dominance and one case of temporary mobility within a family unit during the Late Romano-British period. We also show that the modern patterns of genetic ancestry composition in Modern Britain emerged after the Roman period.

genetics↗

Stimulus degradation impairs performance in a rodent continuous performance test

Sustained attention is a core cognitive domain that is often disrupted in neuropsychiatric disorders. Continuous performance tests (CPTs) are the most common clinical assay of sustained attention. In CPTs, participants produce a behavioral response to target stimuli and refrain from responding to non-target stimuli. Performance in CPTs is measured as the ability to discriminate between targets and non-targets. Rodent versions of CPTs (rCPT) have been developed and validated with both anatomical and pharmacological studies, providing a translational platform for understanding the neurobiology of sustained attention. In human studies, using degraded stimuli (decreased contrast) in CPTs impairs performance and patients with schizophrenia experience a larger decrease in performance compared to healthy controls. In this study, we tested multiple levels of stimulus degradation in a touchscreen version of the CPT in mice. We found that stimulus degradation significantly decreased performance in both males and females. The changes in performance consisted of a decrease in stimulus discrimination, measured as d, and increases in hit reaction time and reaction time variability. These findings are in line with the effects of stimulus degradation in human studies. Overall, female mice demonstrated a more liberal response strategy than males, but response strategy was not affected by stimulus degradation. These data extend the utility of the mouse CPT by demonstrating that stimulus degradation produces equivalent behavioral responses in mice and humans. Therefore, the degraded stimuli rCPT has high translational value as a preclinical assay of sustained attention.

neuroscience↗

Novel full-length major histocompatibility complex class I allele discovery and haplotype definition in pig-tailed macaques

Pig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to rhesus and cynomolgus macaques. In this study, we used Pacific Biosciences single-molecule real-time circular consensus sequencing to describe full-length MHC class I (MHC-I) transcripts for 194 pig-tailed macaques from three breeding centers. We then used the full-length sequences to infer Mane-A and Mane-B haplotypes containing groups of MHC-I transcripts that co-segregate due to physical linkage. In total, we characterized full-length open reading frames (ORFs) for 313 Mane-A, Mane-B, and Mane-I sequences that defined 86 Mane-A and 106 Mane-B MHC-I haplotypes. Pacific Biosciences technology allows us to resolve these Mane-A and Mane-B haplotypes to the level of synonymous allelic variants. The newly defined haplotypes and transcript sequences containing full-length ORFs provide an important resource for infectious disease researchers as certain MHC haplotypes have been shown to provide exceptional control of simian immunodeficiency virus (SIV) replication and prevention of AIDS-like disease in nonhuman primates. The increased allelic resolution provided by Pacific Biosciences sequencing also benefits transplant research by allowing researchers to more specifically match haplotypes between donors and recipients to the level of nonsynonymous allelic variation, thus reducing the risk of graft-versus-host disease.

genetics↗