Extra N-Terminal Residues Have a Profound Effect on the Aggregation Properties of the Potential Yeast Prion Protein Mca1

The metacaspase Mca1 from Saccharomyces cerevisiae displays a Q/N-rich region at its N-terminus reminiscent of yeast prion proteins. In this study, we show that the ability of Mca1 to form insoluble aggregates is modulated by a peptide stretch preceding its putative prion-forming domain. Based on its genomic locus, three potential translational start sites of Mca1 can give rise to two slightly different long Mca1 proteins or a short version, Mca1451/453 and Mca1432, respectively, although under normal physiological conditions Mca1432 is the predominant form expressed. All Mca1 variants exhibit the Q/N-rich regions, while only the long variants Mca1451/453 share an extra stretch of 19 amino acids at their N-terminal end. Strikingly, only long versions of Mca1 but not Mca1432 revealed pronounced aggregation in vivo and displayed prion-like properties when fused to the C-terminal domain of Sup35 suggesting that the N-terminal peptide element promotes the conformational switch of Mca1 protein into an insoluble state. Transfer of the 19 N-terminal amino acid stretch of Mca1451 to the N-terminus of firefly luciferase resulted in increased aggregation of luciferase, suggesting a protein destabilizing function of the peptide element. We conclude that the aggregation propensity of the potential yeast prion protein Mca1 in vivo is strongly accelerated by a short peptide segment preceding its Q/N-rich region and we speculate that such a conformational switch might occur in vivo via the usage of alternative translational start sites

Characterization of the casein gene complex in West Africa goats and description of a new αs1-casein polymorphism

The analysis of casein polymorphisms was carried out in West Africa goat populations: Red Sokoto (n = 57), West African Dwarf Nigeria (n = 27), West African Dwarf Cameroon (n = 39), and Borno (n = 37). The 4 casein genes alphas1 (CSN1S1), beta (CSN2), alphas2 (CSN1S2), and kappa (CSN3) were typed at the DNA level. No null alleles were found in any of the genes analyzed. A PCR single-strand conformation polymorphism method was implemented for the identification of CSN1S1*F allele simultaneously with A/01, B/E, N and the new allele. The allele differed from CSN1S1*B by a synonymous transversion TCG->TCT in the codon corresponding to Ser66 of the mature protein. The new allele, named CSN1S1*B', occurred at a high frequency in all the populations, ranging from 0.295 (West African Dwarf Cameroon) to 0.405 (Borno). A greater frequency was found for alleles associated with high alphas1-casein quantity, as has already been observed in the goat populations from the Mediterranean area. The intermediate E allele occurred only in the Red Sokoto and at a low frequency. The faint F allele occurred in 3 populations at frequencies lower than 0.03. Linkage disequilibrium occurred in all the populations, with highly significant differences in Borno, Red Sokoto, and West Africa Dwarf Nigeria, and significant differences in West Africa Dwarf Cameroon. Only 10 haplotypes showed frequencies >= 0.05 in at least 1 of the 4 populations considered, and the overall frequency was >0.1 only for 4 haplotypes: BAAB, B'ACA, ACAB, and BACA (in the order CSN1S1-CSN2-CSN1S2-CSN3). Haplotype BAAB, postulated as an ancestral haplotype in previous studies, was the most common haplotype in all breeds except Borno, where B'ACA was predominant. The results obtained are of considerable significance given that very little information exists on the subject for African goats. The high frequency of strong alleles in the calcium-sensitive caseins as well as the high linkage disequilibrium found among the casein genes in the African breeds analyzed may suggest that specific casein haplotypes have already been selected due to their advantages for nutrition. Haplotypes providing greater protein and casein content would increase the energy content of milk, thus resulting in more favorable growth and survival of young goats and humans consuming the milk

Do Transportation Network Companies Decrease or Increase Congestion?

This research examines whether transportation network companies (TNCs), such as Uber and Lyft, live up to their stated vision of reducing congestion in major cities. Existing research has produced conflicting results and has been hampered by a lack of data. Using data scraped from the application programming interfaces of two TNCs, combined with observed travel time data, we find that contrary to their vision, TNCs are the biggest contributor to growing traffic congestion in San Francisco. Between 2010 and 2016, weekday vehicle hours of delay increased by 62% compared to 22% in a counterfactual 2016 scenario without TNCs. The findings provide insight into expected changes in major cities as TNCs continue to grow, informing decisions about how to integrate TNCs into the existing transportation system