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  1. The naked mole-rat (Heterocephalus glaber) has fascinated zoologists for at least half a century. It has also generated considerable biomedical interest not only because of its extraordinary longevity, but also because of unusual protective features (e.g. its tolerance of variable oxygen availability), which may be pertinent to several human disease states, including ischemia/reperfusion injury and neurodegeneration. A recent article entitled 'Surprisingly long survival of premature conclusions about naked mole-rat biology' described 28 'myths' which, those authors claimed, are a 'perpetuation of beautiful, but falsified, hypotheses' and impede our understanding of this enigmatic mammal. Here, we re-examine each of these 'myths' based on evidence published in the scientific literature. Following Braude et al., we argue that these 'myths' fall into four main categories: (i) 'myths' that would be better described as oversimplifications, some of which persist solely in the popular press; (ii) 'myths' that are based on incomplete understanding, where more evidence is clearly needed; (iii) 'myths' where the accumulation of evidence over the years has led to a revision in interpretation, but where there is no significant disagreement among scientists currently working in the field; (iv) 'myths' where there is a genuine difference in opinion among active researchers, based on alternative interpretations of the available evidence. The term 'myth' is particularly inappropriate when applied to competing, evidence-based hypotheses, which form part of the normal evolution of scientific knowledge. Here, we provide a comprehensive critical review of naked mole-rat biology and attempt to clarify some of these misconceptions. 
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  2. Abstract

    A variety of rodents have been used as experimental animals in metabolic studies of plasma lipids and lipoproteins. These studies have included understanding the functional role of apolipoprotein A‐I, the major protein on the surface of HDL. Reviewing the genomic database for entries for rodentapoA‐Igenes, it was discovered that the naked mole‐rat (Heterocephalus glaber) gene encoded a protein with a cysteine at residue 28. Previously, two cases have been reported in which human heterozygotes had apoA‐I with cysteine at residues 173 (apoA‐I Milano) or at 151 (apoA‐I Paris). Interestingly, both groups, in spite of having low levels of HDL and moderately elevated plasma triacylglycerols, had no evidence of cardiovascular disease. Moreover, the presence of the cysteine enabled the apoA‐I to form both homodimers and heterodimers. Prior to this report, no other mammalian apoA‐I has been found with a cysteine in its sequence. In addition, the encoded naked mole‐rat protein had different amino acids at sites that were conserved in all other mammals. These differences resulted in naked mole‐rat apoA‐I having an unexpected neutral pI value, whereas other mammalian apoA‐I have negative pI values. To verify these sequence differences and to determine if the N‐terminal location of C28 precluded dimer formation, we conducted mass spectrometry analyses of apoA‐I and other proteins associated with HDL. Consistent with the genomic data, our analyses confirmed the presence of C28 and the formation of a homodimer. Analysis of plasma lipids surprisingly revealed a profile similar to the human heterozygotes.

     
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