Controlling and coordinating development in vector-transmitted parasites

Vector-borne parasites cause major human diseases of the developing world, including malaria, human African trypanosomiasis, Chagas disease, leishmaniasis, filariasis, and schistosomiasis. Although the life cycles of these parasites were defined over 100 years ago, the strategies they use to optimize their successful transmission are only now being understood in molecular terms. Parasites are now known to monitor their environment in both their host and vector and in response to other parasites. This allows them to adapt their developmental cycles and to counteract any unfavorable conditions they encounter. Here, I review the interactions that parasites engage in with their hosts and vectors to maximize their survival and spread.     

The catalytic cross-coupling of unactivated arenes

The industrially important coupling of aromatic compounds has generally required differential prefunctionalization of the arene coupling partners with a halide and an electropositive group. Here we report that palladium, in conjunction with a copper oxidant, can catalyze the cross-coupling of N-acetylindoles and benzenes in high yield and high regioselectivity across a range of indoles without recourse to activating groups. These reactions are completely selective for arene cross-coupling, with no products arising from indole or benzene homo-coupling detected by spectroscopic analysis. This efficient reactivity should be useful in the design of other oxidative arene cross-couplings as well.     

Kilimanjaro ice core records: evidence of holocene climate change in tropical Africa

Six ice cores from Kilimanjaro provide an approximately 11.7-thousand-year record of Holocene climate and environmental variability for eastern equatorial Africa, including three periods of abrupt climate change: approximately 8.3, approximately 5.2, and approximately 4 thousand years ago (ka). The latter is coincident with the "First Dark Age," the period of the greatest historically recorded drought in tropical Africa. Variable deposition of F- and Na+ during the African Humid Period suggests rapidly fluctuating lake levels between approximately 11.7 and 4 ka. Over the 20th century, the areal extent of Kilimanjaro's ice fields has decreased approximately 80%, and if current climatological conditions persist, the remaining ice fields are likely to disappear between 2015 and 2020.     

Human-specific gain of function in a developmental enhancer

Changes in gene regulation are thought to have contributed to the evolution of human development. However, in vivo evidence for uniquely human developmental regulatory function has remained elusive. In transgenic mice, a conserved noncoding sequence (HACNS1) that evolved extremely rapidly in humans acted as an enhancer of gene expression that has gained a strong limb expression domain relative to the orthologous elements from chimpanzee and rhesus macaque. This gain of function was consistent across two developmental stages in the mouse and included the presumptive anterior wrist and proximal thumb. In vivo analyses with synthetic enhancers, in which human-specific substitutions were introduced into the chimpanzee enhancer sequence or reverted in the human enhancer to the ancestral state, indicated that 13 substitutions clustered in an 81-base pair module otherwise highly constrained among terrestrial vertebrates were sufficient to confer the human-specific limb expression domain.