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Biology subjects

Cavalieri, R.

Publications and source records attributed to Cavalieri, R..

2 recordsLinked to original sources

Lack of paternal silencing and ecotype-specific expression in head and body lice hybrids.

Paternal genome elimination (PGE) is a non-Mendelian inheritance system in which males develop from fertilised eggs but their paternally-inherited chromosomes are eliminated before or during spermatogenesis. Therefore, PGE males only transmit their maternally inherited set of chromosomes to their offspring. PGE has been described in numerous arthropod species, many of which are pests or parasites, posing a severe economic burden on crop production and/or with implications for human health. In order to understand how PGE has evolved on the molecular level, to potentially develop novel control strategies, we need to examine species which display basal forms of PGE. The human louse, Pediculus humanus, represents an ideal model system to understand the molecular underpinnings of PGE. In this study we analysed parent-of-origin allele specific expression patterns in male offspring of crosses between head and body lice ecotypes. We have shown that hybrid adult males of P. humanus display biparental gene expression, which constitutes the first known case of a species with PGE in which genetic activity of paternal chromosomes in the soma is not affected by embryonic heterochromatinization or (partial or complete) elimination. We have also identified maternally-biased genes (potentially imprinted genes) which may be involved in the elimination of paternal chromosomes during spermatogenesis. Finally, we have identified genes which show ecotype-specific expression bias. Given the low genetic diversity between ecotypes this is suggestive for a role of epigenetic processes in ecotype differences. These findings have implications for models of pediculicide resistance in human lice and for the development of novel epigenetic-mediated control strategies.

evolutionary biology↗

Activating ligands of Uncoupling protein 1 identified by rapid membrane protein thermostability shift analysis

Uncoupling protein 1 (UCP1) catalyzes mitochondrial proton leak in brown adipose tissue for heat production, and may combat metabolic disease if activated in humans. During the adrenergic stimulation of brown adipocytes, free fatty acids generated from lipolysis activate UCP1 via an unclear interaction. Here, we have utilized membrane protein thermostability shift analysis to characterize the interaction of activating molecules with purified UCP1. We reveal that activators influence the protein through a specific destabilizing interaction, behaving as transport substrates that shift UCP1 to a less stable conformation of a transport cycle. Through the detection of specific stability shifts in screens, we identify novel activators, including the drug ibuprofen, where ligand analysis indicates a relatively wide structural specificity for interacting molecules. Ibuprofen induces UCP1 activity in liposomes and isolated brown fat mitochondria, but not in cultured brown adipocytes. Though the drug does induce activity in UCP1-expressing HEK293 cells, demonstrating that the targeting of UCP1 in cells by approved drugs is in principle achievable as a therapeutic avenue, but requires variants with more effective delivery in brown adipocytes.

biochemistry↗