In vivo regulation of hemoglobin phenotypes of developing Rana catesbeiana

We have examined the effects of phenylhydrazine-induced anemia on the in vivo synthesis of specific hemoglobins at larval, metamorphic, and post-metamorphic stages of the bullfrog Rana catesbeiana, and have found that at all stages the animals qualitatively and quantitatively regenerate their pre-anemia hemoglobin profiles, with one exception: Animals approaching or undergoing the metamorphic hemoglobin switch synthesize only adult hemoglobin during recovery from anemia. We conclude that the ontogenetic progression of hemoglobins in R. catesbeiana is regulated at the level of differentiation of distinct erythroid cell lines, each committed to expressing a particular hemoglobin phenotype; this regulation is unperturbed by anemia.     

Leptin activation of mTOR pathway in intestinal epithelial cell triggers lipid droplet formation,cytokine production and increased cell proliferation

Accumulating evidence suggests that obesity and enhanced inflammatory reactions are predisposing conditions for developing colon cancer. Obesity is associated with high levels of circulating leptin. Leptin is an adipocytokine that is secreted by adipose tissue and modulates immune response and inflammation. Lipid droplets (LD) are organelles involved in lipid metabolism and production of inflammatory mediators, and increased numbers of LD were observed in human colon cancer. Leptin induces the formation of LD in macrophages in a PI3K/mTOR pathway-dependent manner. Moreover, the mTOR is a serine/threonine kinase that plays a key role in cellular growth and is frequently altered in tumors. We therefore investigated the role of leptin in the modulation of mTOR pathway and regulation of lipid metabolism and inflammatory phenotype in intestinal epithelial cells (IEC-6 cells). We show that leptin promotes a dose- and time-dependent enhancement of LD formation. The biogenesis of LD was accompanied by enhanced CXCL1/CINC-1, CCL2/MCP-1 and TGF-β production and increased COX-2 expression in these cells. We demonstrated that leptin-induced increased phosphorylation of STAT3 and AKT and a dose and time-dependent mTORC activation with enhanced phosphorilation of the downstream protein P70S6K protein. Pre-treatment with rapamycin significantly inhibited leptin effects in LD formation, COX-2 and TGF-β production in IEC-6 cells. Moreover, leptin was able to stimulate the proliferation of epithelial cells on a mTOR-dependent manner. We conclude that leptin regulates lipid metabolism, cytokine production and proliferation of intestinal cells through a mechanism largely dependent on activation of the mTOR pathway, thus suggesting that leptin-induced mTOR activation may contribute to the obesity-related enhanced susceptibility to colon carcinoma.     

Synthesis and characterization of the chromium(III) complexes of ethylene cross-bridged cyclam and cyclen ligands

Dichloro(4,10-dimethyl-1,4,7,10-tetraazabicyclo[5.5.2]tetradecane)chromium(III) chloride, Dichloro(4,10-dibenzyl-1,4,7,10-tetraazabicyclo[5.5.2]tetradecane) chromium(III) chloride, and Dichloro(4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2] hexadecane)chromium)(III) chloride have been prepared by the reaction of anhydrous chromium(III) chloride with the appropriate cross-bridged tetraazamacrocycle. Aquation of these complexes proved difficult, but Chlorohydroxo(4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane)chromium)(III) chloride was synthesized directly from chromium(II) chloride complexation followed by exposure or the reaction to air in the presence of water. The four complexes were characterized by X-ray crystal structure determination. All contain the chromium(III) ion in a distorted octahedral geometry and the macrocycle in the cis-V configuration, as dictated by the ethylene cross-bridge. Further characterization of the hydroxo complex reveals a magnetic moment of μ_eff = 3.95 B.M. and electronic absorbtions in acetonitrile at λ_max = 583 nm (ε = 65.8 L/cm mol), 431 nm (ε = 34.8 L/cm mol) and 369 nm (ε = 17 L/cm mol).     

Reconstructing Native American Migrations from Whole-Genome and Whole-Exome Data

There is great scientific and popular interest in understanding the genetic history of populations in the Americas. We wish to understand when different regions of the continent were inhabited, where settlers came from, and how current inhabitants relate genetically to earlier populations. Recent studies unraveled parts of the genetic history of the continent using genotyping arrays and uniparental markers. The 1000 Genomes Project provides a unique opportunity for improving our understanding of population genetic history by providing over a hundred sequenced low coverage genomes and exomes from Colombian (CLM), Mexican-American (MXL), and Puerto Rican (PUR) populations. Here, we explore the genomic contributions of African, European, and especially Native American ancestry to these populations. Estimated Native American ancestry is in MXL, in CLM, and in PUR. Native American ancestry in PUR is most closely related to populations surrounding the Orinoco River basin, confirming the Southern America ancestry of the Taíno people of the Caribbean. We present new methods to estimate the allele frequencies in the Native American fraction of the populations, and model their distribution using a demographic model for three ancestral Native American populations. These ancestral populations likely split in close succession: the most likely scenario, based on a peopling of the Americas thousand years ago (kya), supports that the MXL Ancestors split kya, with a subsequent split of the ancestors to CLM and PUR kya. The model also features effective populations of in Mexico, in Colombia, and in Puerto Rico. Modeling Identity-by-descent (IBD) and ancestry tract length, we show that post-contact populations also differ markedly in their effective sizes and migration patterns, with Puerto Rico showing the smallest effective size and the earlier migration from Europe. Finally, we compare IBD and ancestry assignments to find evidence for relatedness among European founders to the three populations.     

Interactive singing of a male Mueller's gibbon with a simulated neighbor

This study provides evidence for interactive singing, or countersinging, in the dawn song of a male Mueller's gibbon. Tape-recorded answering calls from a simulated neighbor were initiated at the subject's baseline rate (every 18 sec), then successively at every 14 sec, 10 sec, 18 sec, 22 sec, and 26 sec. Two types of evidence for interactive singing were considered. First, the subject's initiation rate significantly increased when the initiation rate of the simulated neighbor increased (but did not decrease when the simulated neighbor's rate decreased). Second, the subject's rate of interruption of the simulated neighbor's vocalizations remained at the same low level regardless of the initiation rate of the simulated neighbor; these interruption rates were, in all cases, significantly lower than would have been expected by chance if interactive singing were not occurring. Evolutional value of interactive singing is considered in relation to demonstration of individual fitness and achievement of clear communication between neighboring groups.