Synthesis of a novel conformationally restricted Val-Phe dipeptidomimetic.

A method for the synthesis of (3(R,S),6S,11b(R,S))-1,3,4,6,7,11b-hexahydro-4-oxo-3-phthalimidopyrido[2,1-a]isoquinoline-6-carboxylic acid 2 as a new conformationally restricted dipeptidomimetic of Val-Phe is reported. It involved cyclisation via an intramolecular electrophilic addition at the reactive bridgehead carbon. This new scaffold can be used as a building block in the preparation of libraries of peptidomimetics.     

Bloom syndrome patients and mice display accelerated epigenetic aging

Bloom syndrome (BSyn) is an autosomal recessive disorder caused by variants in the BLM gene, which is involved in genome stability. Patients with BSyn present with poor growth, sun sensitivity, mild immunodeficiency, diabetes, and increased risk of cancer, most commonly leukemias. Interestingly, patients with BSyn do not have other signs of premature aging such as early, progressive hair loss and cataracts. We set out to determine epigenetic age in BSyn, which can be a better predictor of health and disease over chronological age. Our results show for the first time that patients with BSyn have evidence of accelerated epigenetic aging across several measures in blood lymphocytes, as compared to carriers. Additionally, homozygous Blm mice exhibit accelerated methylation age in multiple tissues, including brain, blood, kidney, heart, and skin, according to the brain methylation clock. Overall, we find that Bloom syndrome is associated with accelerated epigenetic aging effects in multiple tissues and more generally a strong effect on CpG methylation levels.     

Response of juveniles of seven forest tree species and their populations to different combinations of simulated climate change-related stressors: spring-frost,heat, drought,increased UV radiation and ozone concentration under elevated CO2 level

Journal of Plant Research - The study aimed to assess response of juvenile progeny of seven forest tree species, Pinus sylvestris, Picea abies, Betula pendula, Alnus glutinosa, Populus tremula,...