How ancestral subsistence strategies solve salmon starvation and the “protein problem” of Pacific Rim resources

This article provides a theoretical treatment of hunter–gatherer diet and physiology. Through a synthesis of nutritional studies, informed by ethno-archaeological data, we examine the risk of protein-rich diets for human survival, and how societies circumvent "salmon starvation" in the northeastern Pacific Rim. Fundamental nutritional constraints associated with salmon storage and consumption counter long-standing assumptions about the engine of cultural evolution in the region. Excess consumption of lean meat can lead to protein poisoning, termed by early explorers “rabbit starvation.” While consumption of fats and carbohydrates is widely portrayed as a pathway to “offsetting” protein thresholds, there are true limits to the amount of protein individuals can consume, and constraints are most extreme for smaller individuals, children, and pregnant/nursing mothers. While this problem is not usually perceived as associated with fish, the risk of protein poisoning limits the amount of low-fat fish that people can eat safely. Compared with smaller, mass-harvested species (e.g., eulachon), dried salmon are exceedingly lean. Under certain circumstances fattier foods (small forage fish, marine mammals, whales, and even bears) or carbohydrate-rich plants may have been preferred not just for taste but to circumvent this “dietary protein ceiling.” Simply put, “salmon specialization” cannot evolve without access to complimentary caloric energy through fat-rich or carbohydrate-rich resources. By extension, the evolution of storage-based societies requires this problem be solved prior to or in tandem with-salmon intensification. Without such solutions, increased mortality and reproductive rates would have made salmon reliance unsustainable. This insight is in line with genomic research suggesting protein toxicity avoidance was a powerful evolutionary force, possibly linked to genetic adaptations among First Americans. It is also relevant to evaluating the plausibility of other purportedly “focal” economies and informs understanding of the many solutions varied global societies have engineered to overcome physiological protein limits.     

On the mechanism of isomerization of α-hydroxypropionaldehyde to hydroxyacetone

Dimeric lactaldehyde and lactaldehyde-2-d in anhydrous or aqueous pyridine isomerize to hydroxyacetone. The isomerization is catalyzed by protic species that includes self-catalysis by the starting material and product, and catalysis by water and other Brönsted acids. The deuterium isotope effect which has values between 4 and 7, the isotopic exchange data, and the proton nmr assignment of the open dimer are consonant with the enediol mechanism with a rate-determining step involving the enolization of the open dimer.     

Impacts of the −1 Amino Acid on Yeast Production of Protein-Intein Fusions

Expressing antibodies as fusions to the non-self-cleaving Mxe GyrA intein allows for site-specific chemical functionalization via expressed protein ligation. It is highly desirable to maximize the yield of functionalizable protein; and previously an evolved intein, 202-08, was identified that could increase protein fusion production in yeast. Given that the −1 amino acid residue upstream of inteins can affect cleavage efficiency, we examined the effects of amino acid variability at this position on 202-08 intein cleavage efficiency and secretion yield. Varying the −1 residue resulted in a wide range of cleavage behaviors with some amino acids yielding substantial autocleaved product that could not be functionalized. Autocleavage was noticeably higher with the 202-08 intein compared with the wild-type Mxe GyrA intein and resulted directly from the catalytic activity of the intein. Refeeding of production cultures with nitrogen base and casamino acids reduced, but did not eliminate autocleavage, while increasing protein-intein production up to seven-fold. Importantly, two amino acids, Gly and Ala, at the −1 position resulted in good cleavage efficiency with no undesirable autocleavage, and can be used in concert with refeeding strategies to increase total functionalizable protein yield for multiple protein fusion partners. Taken together, we describe an optimized yeast expression platform for protein-intein fusions. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2736, 2019     

Genomic blot hybridization as a tool of phylogenetic analysis: Evolutionary divergence in the genusDrosophila

Summary Comparative, quantitative Southern analysis of genomic DNA, using single-copy sequence probes, potentially is valuable for phylogenetic analysis. We have examined 27Drosophila species, belonging to two subgenera, seven species groups, and ten subgroups, using a variety of cloned and characterized probes: twelve cloned sequences fromD. melanogaster, two fromD. pseudoobscura, and two fromD. grimshawi. The data are generally congruent with accepted phylogenetic relationships inDrosophila, and confirm or clarify some previously uncertain relationships. The potential and limitations of the method are discussed.Presented at the FEBS Symposium on Genome Organization and Evolution, held in Crete, Greece, September 1–5, 1986     

Characterising the Mucosal and Systemic Immune Responses to Experimental Human Hookworm Infection

The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13) and regulatory (IL-10 and TGF-β) response, with some evidence of a Th1 (IFN-γ and IL-2) response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17) response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases.