Early life changes in histone landscape protect against age-associated amyloid toxicities through HSF-1-dependent regulation of lipid metabolism.

Transient events during development can exert long-lasting effects on organismal lifespan. Here we demonstrate that exposure of Caenorhabditis elegans to reactive oxygen species during development protects against amyloid-induced proteotoxicity later in life. We show that this protection is initiated by the inactivation of the redox-sensitive H3K4me3-depositing COMPASS complex and conferred by a substantial increase in the heat-shock-independent activity of heat shock factor 1 (HSF-1), a longevity factor known to act predominantly during C. elegans development. We show that depletion of HSF-1 leads to marked rearrangements of the organismal lipid landscape and a significant decrease in mitochondrial ß-oxidation and that both lipid and metabolic changes contribute to the protective effects of HSF-1 against amyloid toxicity. Together, these findings link developmental changes in the histone landscape, HSF-1 activity and lipid metabolism to protection against age-associated amyloid toxicities later in life.

Effective Generation of Gynogenic Haploid Zebrafish Embryos Using Low Dosage of UV Rays.

The phenomenon of phenotype manifestation when the single allele in a haploid is affected is desirable for uncovering recessive mutations expeditiously in a diploid organism. However, experimentally generated haploids manifest extensive lethality and a cluster of non-specific developmental defects known as the haploid syndrome. This precludes the use of experimentally generated haploids for genetic screens due to an insufficient number of embryos for screening and the possibility of phenotypes due to the affected gene being masked by the haploid syndrome. We show here that gynogenic haploid zebrafish can be generated by irradiation of spermatozoa with a lower UV dosage than is currently used. This strategy results in reduced haploid lethality, incidence and severity of haploid syndrome. When viewed in the context of zebrafish as a genetically tractable model organism for forward and reverse genetic strategies, these results place zebrafish in a unique niche as a vertebrate in which haploid genetic screens for developmental phenotypes could be successfully attempted.