Genetically-encoded fragment-based discovery of glycopeptide ligands for DC-SIGN

We have employed genetically-encoded fragment-based discovery to identify novel glycopeptides with affinity for the dendritic cell receptor DC-SIGN. Starting from libraries of 10⁸ mannose-conjugated peptides, we identified glycopeptides that exhibited up to a 650-fold increase in multivalent binding affinity for DC-SIGN, which is also preserved in cells. Monovalently, our most potent glycopeptides have a similar potency to a Man₃ oligosaccharide, representing a 15-fold increase in activity compared to mannose. These compounds represent the first examples of glycopeptide ligands that target the CRD of DC-SIGN. The natural framework of glycopeptide conjugates and the simplicity of orthogonal conjugation to make these glycopeptides anticipates a promising future for development of DC-SIGN-targeting moieties.     

The origins and early elaboration of projectile technology

The ability of Homo sapiens to kill prey at a distance is arguably one of the catalysts for our current ecological dominance. Many researchers have suggested its origins lie in the African Middle Stone Age or the European Middle Palaeolithic (～300‐30 thousand years ago), but the perishable components of armatures rarely preserve. Most research on this subject therefore emphasises analysis of armature tip size, shape, and diagnostic impacts or residues. Other lines of evidence have included human skeletal anatomy or analyses of the species composition of faunal assemblages. Projectile Impact Marks (PIMs) on archaeofaunal remains offer an ideal complement to this work, but their potential has been restricted mainly to the later Eurasian zooarchaeological record. A review of current evidence and approaches shows that systematic PIM research could add much to our understanding of early projectile technology, especially in Africa.     

Rock lobster hepatopancreas consumption data for dietary exposure assessment among recreational harvesters in Tasmania and South Australia

In 2012 and 2015, blooms of Alexandrium tamarense occurred in Tasmania, Australia, and paralytic shellfish toxins (PST) were identified in the hepatopancreas of Southern Rock Lobsters. The human health risk was unclear, because consumption data were not available for lobster hepatopancreas. Thus, the aim of this study was to investigate the types of lobster tissues consumed, hepatopancreas portion size, and consumption format (boiled, steamed, raw, etc.), for Tasmanian and South Australian recreational harvesters.

A significant proportion of harvesters (15%) eat lobster hepatopancreas, with the majority consuming it as a dipping sauce for cooked (boiled or steamed) lobster meat. Two different methods were used to estimate portion size, a recollection-based food consumption questionnaire (FCQ) and a prospective Food Diary – mean portion size estimates showed good agreement: 3.4 g and 4.8 g, respectively. These results are critical for assessing the exposure of recreational harvesters to acute contaminants, such as PST, in lobster hepatopancreas. Results from the FCQ showed that lobster hepatopancreas is not consumed as often as white meat, suggesting that exposure to contaminants in hepatopancreas may be less frequent than white meat. This should be considered when evaluating human health risk from repeated or long term (chronic) exposure to contaminants in lobsters.     

A practical synthesis of xylo- and arabinofuranoside precursors by diastereoselective reduction using Corey-Bakshi-Shibata catalyst

The Corey-Bakshi-Shibata (CBS) catalyst provides an efficient mechanism to reduce ketones and achieve desired enantiopure alcohols. Herein, the diastereoselective reduction of C-2′ and C-3′-keto ribofuranoside derivatives to the corresponding arabino- and xylofuranosides in greater than 95% diastereomeric excess is reported. The stereo-directed substitution with an azido group as well as the synthesis of prodrugs cytarabine and vidarabine are also described. The reported strategy offers superior diastereoselectivity, shorter reaction times, and obviates cooling required with comparable protocols involving achiral reductants.     

The companion dog as a model for human aging and mortality

Around the world, human populations have experienced large increases in average lifespan over the last 150 years, and while individuals are living longer, they are spending more years of life with multiple chronic morbidities. Researchers have used numerous laboratory animal models to understand the biological and environmental factors that influence aging, morbidity, and longevity. However, the most commonly studied animal species, laboratory mice and rats, do not experience environmental conditions similar to those to which humans are exposed, nor do we often diagnose them with many of the naturally occurring pathologies seen in humans. Recently, the companion dog has been proposed as a powerful model to better understand the genetic and environmental determinants of morbidity and mortality in humans. However, it is not known to what extent the age‐related dynamics of morbidity, comorbidity, and mortality are shared between humans and dogs. Here, we present the first large‐scale comparison of human and canine patterns of age‐specific morbidity and mortality. We find that many chronic conditions that commonly occur in human populations (obesity, arthritis, hypothyroidism, and diabetes), and which are associated with comorbidities, are also associated with similarly high levels of comorbidity in companion dogs. We also find significant similarities in the effect of age on disease risk in humans and dogs, with neoplastic, congenital, and metabolic causes of death showing similar age trajectories between the two species. Overall, our study suggests that the companion dog may be an ideal translational model to study the many complex facets of human morbidity and mortality.