Hominids adapted to metabolize ethanol long before human-directed fermentation.

Paleogenetics is an emerging field that resurrects ancestral proteins from now-extinct organisms to test, in the laboratory, models of protein function based on natural history and Darwinian evolution. Here, we resurrect digestive alcohol dehydrogenases (ADH4) from our primate ancestors to explore the history of primate-ethanol interactions. The evolving catalytic properties of these resurrected enzymes show that our ape ancestors gained a digestive dehydrogenase enzyme capable of metabolizing ethanol near the time that they began using the forest floor, about 10 million y ago. The ADH4 enzyme in our more ancient and arboreal ancestors did not efficiently oxidize ethanol. This change suggests that exposure to dietary sources of ethanol increased in hominids during the early stages of our adaptation to a terrestrial lifestyle. Because fruit collected from the forest floor is expected to contain higher concentrations of fermenting yeast and ethanol than similar fruits hanging on trees, this transition may also be the first time our ancestors were exposed to (and adapted to) substantial amounts of dietary ethanol.

Novel joint cupping clinical maneuver for ultrasonographic detection of knee joint effusions.

INTRODUCTION: Knee effusions occur due to traumatic and atraumatic causes. Clinical diagnosis currently relies on several provocative techniques to demonstrate knee joint effusions. Portable bedside ultrasonography (US) is becoming an adjunct to diagnosis of effusions. We hypothesized that a US approach with a clinical joint cupping maneuver increases sensitivity in identifying effusions as compared to US alone. METHODS: Using unembalmed cadaver knees, we injected fluid to create effusions up to 10 mL. Each effusion volume was measured in a lateral transverse location with respect to the patella. For each effusion we applied a joint cupping maneuver from an inferior approach, and re-measured the effusion. RESULTS: With increased volume of saline infusion, the mean depth of effusion on ultrasound imaging increased as well. Using a 2-mm cutoff, we visualized an effusion without the joint cupping maneuver at 2.5 mL and with the joint cupping technique at 1 mL. Mean effusion diameter increased on average 0.26 cm for the joint cupping maneuver as compared to without the maneuver. The effusion depth was statistically different at 2.5 and 7.5 mL (P < .05). CONCLUSIONS: Utilizing a joint cupping technique in combination with US is a valuable tool in assessing knee effusions, especially those of subclinical levels. Effusion measurements are complicated by uneven distribution of effusion fluid. A clinical joint cupping maneuver concentrates the fluid in one recess of the joint, increasing the likelihood of fluid detection using US.

The natural history of class I primate alcohol dehydrogenases includes gene duplication, gene loss, and gene conversion.

BACKGROUND: Gene duplication is a source of molecular innovation throughout evolution. However, even with massive amounts of genome sequence data, correlating gene duplication with speciation and other events in natural history can be difficult. This is especially true in its most interesting cases, where rapid and multiple duplications are likely to reflect adaptation to rapidly changing environments and life styles. This may be so for Class I of alcohol dehydrogenases (ADH1s), where multiple duplications occurred in primate lineages in Old and New World monkeys (OWMs and NWMs) and hominoids. METHODOLOGY/PRINCIPAL FINDINGS: To build a preferred model for the natural history of ADH1s, we determined the sequences of nine new ADH1 genes, finding for the first time multiple paralogs in various prosimians (lemurs, strepsirhines). Database mining then identified novel ADH1 paralogs in both macaque (an OWM) and marmoset (a NWM). These were used with the previously identified human paralogs to resolve controversies relating to dates of duplication and gene conversion in the ADH1 family. Central to these controversies are differences in the topologies of trees generated from exonic (coding) sequences and intronic sequences. CONCLUSIONS/SIGNIFICANCE: We provide evidence that gene conversions are the primary source of difference, using molecular clock dating of duplications and analyses of microinsertions and deletions (micro-indels). The tree topology inferred from intron sequences appear to more correctly represent the natural history of ADH1s, with the ADH1 paralogs in platyrrhines (NWMs) and catarrhines (OWMs and hominoids) having arisen by duplications shortly predating the divergence of OWMs and NWMs. We also conclude that paralogs in lemurs arose independently. Finally, we identify errors in database interpretation as the source of controversies concerning gene conversion. These analyses provide a model for the natural history of ADH1s that posits four ADH1 paralogs in the ancestor of Catarrhine and Platyrrhine primates, followed by the loss of an ADH1 paralog in the human lineage.