Natural proteome diversity links aneuploidy tolerance to protein turnover.

Accessing the natural genetic diversity of species unveils hidden genetic traits, clarifies gene functions and allows the generalizability of laboratory findings to be assessed. One notable discovery made in natural isolates of Saccharomyces cerevisiae is that aneuploidy-an imbalance in chromosome copy numbers-is frequent1,2 (around 20%), which seems to contradict the substantial fitness costs and transient nature of aneuploidy when it is engineered in the laboratory3-5. Here we generate a proteomic resource and merge it with genomic1 and transcriptomic6 data for 796 euploid and aneuploid natural isolates. We find that natural and lab-generated aneuploids differ specifically at the proteome. In lab-generated aneuploids, some proteins-especially subunits of protein complexes-show reduced expression, but the overall protein levels correspond to the aneuploid gene dosage. By contrast, in natural isolates, more than 70% of proteins encoded on aneuploid chromosomes are dosage compensated, and average protein levels are shifted towards the euploid state chromosome-wide. At the molecular level, we detect an induction of structural components of the proteasome, increased levels of ubiquitination, and reveal an interdependency of protein turnover rates and attenuation. Our study thus highlights the role of protein turnover in mediating aneuploidy tolerance, and shows the utility of exploiting the natural diversity of species to attain generalizable molecular insights into complex biological processes.

Singlet Oxygen Photooxidation of Peptidic Oxazoles and Thiazoles.

Oxazoles and thiazoles are commonly found moieties in nonribosomal peptides (NRPs) and ribosomally synthesized post-translationally modified peptides (RiPPs), which are important biomolecules present in the environment and in natural waters. From previous studies, they seem susceptible to oxidation by singlet oxygen (1O2); therefore, we designed and synthesized model oxazole- and thiazole-peptides and measured their 1O2 bimolecular reaction rate constants, showing slow photooxidation under environmental conditions. We reasoned their stability through the electron-withdrawing effect of the carboxamide substituent. Reaction products were elucidated and support a reaction mechanism involving cycloaddition followed by a series of rearrangements. The first 1O2 bimolecular reaction rate constant for a RiPP, the thiazole-containing peptide Aerucyclamide A, was measured and found in good agreement with the model peptide's rate constant, highlighting the potential of using model peptides to study the transformations of other environmentally relevant NRPs and RiPPs.

InSPAL: A Novel Immersive Virtual Learning Programme.

In this paper we introduce The Interactive Sensory Program for Affective Learning (InSPAL) a pioneering virtual learning programme designed for the severely intellectually disabled (SID) students, who are having cognitive deficiencies and other sensory-motor handicaps, and thus need more help and attention in overcoming their learning difficulties. Through combining and integrating interactive media and virtual reality technology with the principles of art therapy and relevant pedagogical techniques, InSPAL aims to strengthen SID students' pre-learning abilities, promote their self-awareness, decrease behavioral interferences with learning as well as social interaction, enhance their communication and thus promote their quality of life. Results of our study show that students who went through our programme were more focused, and the ability to do things more independently increased by 15%. Moreover, 50% of the students showed a marked improvement in the ability to raise their hands in response, thus increasing their communication skills. The use of therapeutic interventions enabled a better control to the body, mind and emotions, resulting a greater performance and better participation.