Showing papers by "Richard Lathe published in 2019"
TL;DR: The potential abiotic generation of isoprene, the crucial role that polyprene terpenoids played in early membranes and cellular life, and that endocrinology from microbes to plants and vertebrates is firmly grounded on Ruzicka's pivotal insights into the structure and function of terpenes are addressed.
Abstract: The year 2019 marks the 80th anniversary of the 1939 Nobel Prize in Chemistry awarded to Leopold Ruzicka (1887-1976) for work on higher terpene molecular structures, including the first chemical synthesis of male sex hormones. Arguably his crowning achievement was the 'biogenetic isoprene rule', which helped to unravel the complexities of terpenoid biosynthesis. The rule declares terpenoids to be enzymatically cyclized products of substrate alkene chains containing a characteristic number of linear, head-to-tail condensed, C5 isoprene units. The number of repeat isoprene units dictates the type of terpene produced (i.e., 2, monoterpene; 3, sesquiterpene; 4, diterpene, etc.). In the case of triterpenes, six C5 isoprene units combine into C30 squalene, which is cyclized into one of the signature carbon skeletons from which myriad downstream triterpenoid structures are derived, including sterols and steroids. Ruzicka also had a keen interest in the origin of life, but the pivotal role of terpenoids has generally been overshadowed by nucleobases, amino acids, and sugars. To redress the balance, we provide a historical and evolutionary perspective. We address the potential abiotic generation of isoprene, the crucial role that polyprene terpenoids played in early membranes and cellular life, and emphasize that endocrinology from microbes to plants and vertebrates is firmly grounded on Ruzicka's pivotal insights into the structure and function of terpenes. A harmonizing feature is that all known lifeforms (including bacteria) biosynthesize triterpenoid substances that are essential for cellular membrane formation and function, from which signaling molecules such as steroid hormones and cognate receptors are likely to have evolved.
32 citations
TL;DR: The findings suggest that the hippocampus acts as an integrator of body status, extending its role in context-dependent memory encoding from ‘where’ and ‘when’ to ‘how I feel’.
Abstract: The primeval function of the mammalian hippocampus (HPC) remains uncertain. Implicated in learning and memory, spatial navigation, and neuropsychological disorders, evolutionary theory suggests that the HPC evolved from a primeval chemosensory epithelium. Internal sensing deficits in patients with HPC lesions argue that internal sensing may be conserved in higher vertebrates. We studied the expression of 250 endocrine receptors in mouse brain. Key findings are (i) the proportions and levels of endocrine receptor expression in the HPC are significantly higher than in all other comparable brain regions. (ii) Surprisingly, the distribution of endocrine receptor expression within mouse HPC was found to be highly structured: receptors signaling ‘challenge’ are segregated in dentate gyrus (DG), whereas those signaling ‘sufficiency’ are principally found in cornu ammonis (CA) regions. Selective expression of endocrine receptors in the HPC argues that internal sensing remains a core feature of hippocampal function. Further, we report that ligands of DG receptors predominantly inhibit both synaptic potentiation and neurogenesis, whereas CA receptor ligands conversely promote both synaptic potentiation and neurogenesis. These findings suggest that the hippocampus acts as an integrator of body status, extending its role in context-dependent memory encoding from ‘where’ and ‘when’ to ‘how I feel’. Implications for anxiety and depression are discussed.
8 citations
TL;DR: Commentary in Neurotherapeutics critically addresses the earlier report by Tzeng et al. that aggressive antiviral treatment against herpes simplex virus (HSV) was associated with a later decrease in the incidence of Alzheimer’s disease (AD).
6 citations
TL;DR: A systematic analysis of candidate molecular species present in hamster brain infected with scrapie strain 263K is begun, arguing that the major species of these 8 RNA molecules are unlikely to correspond to the etiologic agent of the TSEs.
Abstract: SUMMARY The identity of the etiologic agent of the transmissible spongiform encephalopathies (TSEs), including bovine spongiform encephalopathy (BSE), scrapie and Creutzfeldt-Jakob disease (CJD), remains unknown. While much attention has been given to the hypothesis that the TSEs may be caused by a proteinaceous infectious agent or ‘prion’, there is considerable evidence to suggest that this hypothesis is incomplete. We have pursued an alternative contention: that the etiologic agent comprises in part a modified and replicating form of an endogenous nucleic acid, probably RNA. The ‘endovirus’ hypothesis contends that the parental molecule is most likely to be a small and highly-structured cellular RNA that can convert to a replicating molecule by a finite number of nucleotide sequence changes. We have begun a systematic analysis of candidate molecular species present in hamster brain infected with scrapie strain 263K. Initial work focussed on the 7S group of small RNAs. Examination of 7-2, 7SK and 7SL failed to reveal differences in abundance and/or sequence between normal and scrapie (263K)-infected hamster brain. Inspection of other possible candidates, including U3, H1/8-2 and novel molecules KR1, nu1 and nu2, similarly failed to provide evidence for scrapie-specific molecular variants; alterations to the KR1 sequence failed to correlate with disease. We present sequences of hamster RNAs 7-2, 7SK, 7SL, H1/8-2, U3, nu1, nu2 and KR1. Together our data so far fail to contradict or confirm the hypothesis, while arguing that the major species of these 8 RNA molecules are unlikely to correspond to the etiologic agent of the TSEs.
1 citations