Evolutionary analyses of the major variant surface antigen-encoding genes reveal population structure of Plasmodium falciparum within and between continents

Malaria remains a major public health problem in many countries. Unlike influenza and HIV, where diversity in immunodominant surface antigens is understood geographically to inform disease surveillance, relatively little is known about the global population structure of PfEMP1, the major variant surface antigen of the malaria parasite Plasmodium falciparum. The complexity of the var multigene family that encodes PfEMP1 and that diversifies by recombination, has so far precluded its use in malaria surveillance. Recent studies have demonstrated that cost-effective deep sequencing of the region of var genes encoding the PfEMP1 DBLα domain and subsequent classification of within host sequences at 96% identity to define unique DBLα types, can reveal structure and strain dynamics within countries. However, to date there has not been a comprehensive comparison of these DBLα types between countries. By leveraging a bioinformatic approach (jumping hidden Markov model) designed specifically for the analysis of recombination within var genes and applying it to a dataset of DBLα types from 10 countries, we are able to describe population structure of DBLα types at the global scale. The sensitivity of the approach allows for the comparison of the global dataset to ape samples of Plasmodium Laverania species. Our analyses show that the evolution of the parasite population emerging out of Africa underlies current patterns of DBLα type diversity. Most importantly, we can distinguish geographic population structure within Africa between Gabon and Ghana in West Africa and Uganda in East Africa. Our evolutionary findings have translational implications in the context of globalization. Firstly, DBLα type diversity can provide a simple diagnostic framework for geographic surveillance of the rapidly evolving transmission dynamics of P. falciparum. It can also inform efforts to understand the presence or absence of global, regional and local population immunity to major surface antigen variants. Additionally, we identify a number of highly conserved DBLα types that are present globally that may be of biological significance and warrant further characterization.     

Overcoming Obstacles to Evolution Education: The OOPSIE Compromise—A Big Mistake

Opt-out policies are typically invoked to excuse students from activities to which they or their parents may have religious objections, such as reciting the Pledge of Allegiance, dissecting animals in a laboratory, or attending sex education classes. Occasionally, however, a school or school district allows students to opt out of academic topics, including, sometimes, evolution. Opt-out policies specifically including evolution are a big mistake—for the students who opt out, for their classmates whose studies are disrupted, and especially for their teachers, who cannot fulfill their duty to instruct their charges about biology without emphasizing evolution.     

Effect of solar eclipse on the behavior of a captive group of chimpanzees (Pan troglodytes)

A captive group of chimpanzees, housed in an outdoor compound at the Yerkes Regional Primate Research Center, was observed during the annular solar eclipse of May 30, 1984. The behavior of each animal was recorded using an instantaneous scan-sampling technique (Altmann: Behaviour 49:227–265, 1974). Beginning 2 days prior to the eclipse and continuing through the day following the eclipse, data were collected from 1100 to 1300 hours daily. At 1214 hours on the day of the eclipse, when the sky began to darken and the temperature began to decrease, solitary females and females with infants moved to the top of a climbing structure. As the eclipse progressed, additional chimpanzees began to congregate on the climbing structure and to orient their bodies in the direction of the sun and moon. At 1223 hours, during the period of maximum eclipse, the animals continued to orient their bodies toward the sun and moon and to turn their faces upward. One juvenile stood upright and gestured in the direction of the sun and moon. Sunlight began to increase at 1225 hours, and as it became brighter, the animals began to descend from the climbing structure. The behaviors exhibited by the group during the period of maximum eclipse were not observed prior to or following the eclipse nor as darkness approached at normal, daily sunset. These data indicate that a solar eclipse, a rare and uncommon environmental event, can influence and modulate the behavior of chimpanzees.     

Role of binding in distribution of furosemide: where is nonrenal clearance?

Furosemide is an acidic drug that binds tightly to anionic binding sites on albumin, but has negligible binding to tissue proteins. As a consequence, it has a low volume of distribution of total drug at steady state (Vdss total), which is less than extracellular fluid volume. With decreases in serum albumin concentration, plasma protein binding decreases, total Vdss increases, and Vdss of free drug decreases in a manner that is quantitatively consistent with no change in tissue binding. The elimination of furosemide is partly by renal clearance of unchanged drug (predominantly because of renal tubule secretion) and partly by nonrenal routes. Glucuronidation appears to occur in extrahepatic sites in dogs and, possibly, humans. Residual nonrenal elimination is not influenced by liver disease but is reduced by probenecid pretreatment and uremia. Furthermore, there is appreciable recovery of 35S-labeled furosemide in feces after i.v. administration without the appearance of 35S in the bile. These observations are consistent with the hypothesis of active secretion of furosemide into the gut. The independent variables of distribution and elimination contribute to determine intersubject variability of plasma concentration-time profiles in health and disease and, therefore, are important in determining the extent and duration of diuretic response.     

The immune-stimulation capacity of liposome-treated red blood cells

Our in vivo studies on a rat model established safety of transfusing liposome-treated red blood cells (RBCs) but identified the potential for immune modulation as related to transfusion efficacy of liposome-treated RBCs. The aim of this study was at assessing the impact of liposome-induced membrane changes on the immune profile of liposome-treated RBCs by (a) evaluating their interaction with endothelial cells and monocytes; and (b) the resulting immune response derived from this interaction, in the form of cytokine release, adhesion molecules expression and phagocytosis. Unilamellar liposomes were synthesized to contain unsaturated phospholipids (1,2-dioleoyl-sn-glycero-3-phosphocholine [DOPC]:CHOL, 7:3?mol%). The human RBCs immune profile was assessed by incubating control and DOPC-treated RBCs with human umbilical vein endothelial cells (HUVECs) and monocytes. Cytokine release measured by Luminex technology, vascular cell adhesion molecule (VCAM)-1 and E-selectin on HUVECs measured by flow cytometry, and the erythrophagocytic activity of monocytes by monocyte monolayer assay (MMA) were determined. Fibroblast growth factor [FGF]-2 was the only cytokine released by HUVECs that remained increased after incubation with DOPC-treated RBCs compared to control throughout storage. The expression of both VCAM-1 (15.3?±?5.6% versus 6.3?±?0.9%, p?=?0.008) and E-selectin (18.0?±?6.3% versus 6.6?±?0.7%, p?=?0.004) by HUVECs were significantly increased after incubation with DOPC-treated RBCs at day 2 of storage. The MMA resulted in phagocytic indexes of zero for both control and DOPC-treated RBCs at day 2 and 42 of storage. The liposome treatment did not result in significant changes to the immune profile of stored DOPC-treated RBCs. These findings combined with previous in vivo results, make liposome treatment a potential candidate for application in RBC preservation and open the possibility for clinical use with other cell types.     

Sex ratios in blue whales from conception onward: effects of space,time, and body size

Deviations from equal sex ratios in mammals can reveal insights into sex-specific growth, survival, movements, and behavior. We assessed blue whale (Balaenoptera musculus) sex ratios based on 21,542 fetal and 311,901 whaling records, finding that males were slightly but significantly more common than females (51.3% fetal, 52.1% postnatal). Antarctic catches shifted from 52.4% male before 1951 to 48.0% male thereafter, even though larger females were preferentially targeted by whalers and should have declined. The southernmost land stations caught more males than those in southern Africa, and at land stations, sex ratios shifted subtly over the course of a year. Pelagic catches demonstrated spatial structure in sex ratios, including more males being caught in the Ross Sea. In utero, the smallest females were often misidentified as males, and there was some evidence for higher prenatal male mortality. Once born, medium-sized blue whales within each region were more often male, while the longest were nearly all female; explained entirely by females growing faster and reaching longer sizes. Overall, though, sex ratios are remarkably close to equality across time, space, and length; with any deviations best explained by faster female growth and size-selective whaling.     

A molecular phylogeny of Equatorial African Lacertidae, with the description of a new genus and species from eastern Democratic Republic of the Congo

Currently, four species of the lacertid lizard genus Adolfus are known from Central and East Africa. We sequenced up to 2,825 bp of two mitochondrial (16S and cyt b) and two nuclear (c-mos and RAG1) genes from 41 samples of Adolfus (representing every species), two species each of Gastropholis and Holaspis, and in separate analyses combined this data with GenBank sequences of all other Eremiadini genera and four Lacertini outgroups. Data from DNA sequences were analyzed with maximum parsimony (PAUP), maximum-likelihood (RAxML) and Bayesian inference (MrBayes) criteria. Results demonstrated that Adolfus is not monophyletic: A. africanus (type species), A. alleni and A. jacksoni are sister taxa, whereas A. vauereselli and a new species from the Itombwe Plateau of Democratic Republic of the Congo are in a separate lineage. Holaspis and Gastropholis were recovered in separate clades. Based on this molecular data, relatively substantial sequence divergence and multiple morphological differences, we describe a new genus of lacertid for the lineage including A. vauereselli and the new Itombwe species. The recognition of this new, endemic genus underscores the conservation importance of the Albertine Rift, especially the Itombwe Plateau, a unique region that is severely threatened by unchecked deforestation, mining and poaching.