Fertilization stimulates lipid peroxidation in the sea urchin egg

Arachidonic acid is rapidly taken-up by Strongylocentrotus purpuratus eggs and eventually incorporated into cellular lipids. During the first few minutes following fertilization the arachidonic acid that has not been incorporated into other lipid forms is oxidized to a hydroxy-fatty acid. In vivo, the time of arachidonic acid conversion coincides with the transient period of increased intracellular free calcium after fertilization. In vitro, this lipid peroxidizing activity has been shown to be initiated by micromolar calcium. Taken together with the presence of Ca2+-stimulated lipase, these results suggest that calcium regulates both the release of polyunsaturated fatty acids from cellular lipids and their subsequent oxidation. The physiological function of lipid hydroxides or hydroperoxides in sea urchin fertilization is unknown. A possibility is that they may be important in regulating the many membrane permeability changes occurring within minutes after fertilization.     

Sphingosine Kinase Activity Is Not Required for Tumor Cell Viability

Sphingosine kinases (SPHKs) are enzymes that phosphorylate the lipid sphingosine, leading to the formation of sphingosine-1-phosphate (S1P). In addition to the well established role of extracellular S1P as a mitogen and potent chemoattractant, SPHK activity has been postulated to be an important intracellular regulator of apoptosis. According to the proposed rheostat theory, SPHK activity shifts the intracellular balance from the pro-apoptotic sphingolipids ceramide and sphingosine to the mitogenic S1P, thereby determining the susceptibility of a cell to apoptotic stress. Despite numerous publications with supporting evidence, a clear experimental confirmation of the impact of this mechanism on tumor cell viability in vitro and in vivo has been hampered by the lack of suitable tool reagents. Utilizing a structure based design approach, we developed potent and specific SPHK1/2 inhibitors. These compounds completely inhibited intracellular S1P production in human cells and attenuated vascular permeability in mice, but did not lead to reduced tumor cell growth in vitro or in vivo. In addition, siRNA experiments targeting either SPHK1 or SPHK2 in a large panel of cell lines failed to demonstrate any statistically significant effects on cell viability. These results show that the SPHK rheostat does not play a major role in tumor cell viability, and that SPHKs might not be attractive targets for pharmacological intervention in the area of oncology.     

Mapping of a quantitative trait locus for morphine withdrawal severity

Chronic morphine exposure results in physical dependence, manifested by physical symptoms during naloxone-precipitated withdrawal. Jumping frequency is widely considered the most sensitive and reliable index of withdrawal intensity in mice. Inbred mouse strains surveyed for naloxone-precipitated withdrawal display large and significant strain differences in jumping frequency, including an approximately tenfold difference between C57BL/6 and 129P3 mice. In the present study, (B6 × 129)F₂ hybrid mice were given daily morphine injections for four days using an escalating dosing schedule, and naloxone-precipitated withdrawal on day 5 was measured. A full-genome scan for linkage to phenotypic data was performed using polymorphic microsatellite markers. Significant linkage was observed between withdrawal jumping frequencies and a 28 cM-wide region of Chromosome 1 (32–60 cM; peak at 51 cM), accounting for 20% of the overall phenotypic variance. Two other suggestive QTLs were found, on Chromosomes 5 and 10, and an additive model fitting all three loci accounted for 43% of the total variance. F₂ mice were also assessed for changes in morphine analgesic potency using the tail-withdrawal test in dose–response studies on days 1 and 4. No linkage was observed between Chromosomes 1, 5, and 10 and morphine analgesic tolerance, suggestive of genetic dissociation of naloxone-precipitated withdrawal from morphine and chronic morphine intake per se. The significant quantitative trait locus for naloxone-precipitated withdrawal severity in morphine-dependent mice, which we name Depmq1, may prove to be of considerable heuristic value once the underlying gene or genes are identified.     

Interactive effects of species richness and species traits on functional diversity and redundancy

The importance of species diversity for ecosystem function has emerged as a key question for conservation biology. Recently, there has been a shift from examining the role of species richness in isolation towards understanding how species interact to effect ecosystem function. Here, we briefly review theoretical predictions regarding species contributions to functional diversity and redundancy and further use simulated data to test combined effects of species richness, number of functional traits, and species differences within these traits on unique species contributions to functional diversity and redundancy, as well as on the overall functional diversity and redundancy within species assemblages. Our results highlighted that species richness and species functional attributes interact in their effects on functional diversity. Moreover, our simulations suggested that functional differences among species have limited effects on the proportion of redundancy of species contributions as well as on the overall redundancy within species assemblages, but that redundancy rather was determined by number of traits and species richness. Our simulations finally indicated scale dependence in the relative effects of species richness and functional attributes, which suggest that the relative influence of these factors may affect individual contributions differently compared to the overall ecosystem function of species assemblages. We suggest that studies on the relationship between biological diversity and ecosystem function will benefit from focusing on multiple processes and ecological interactions, and that the relative functional attributes of species will have pivotal roles for the ecosystem function of a given species assembly.     

Early agriculture and crop transmission among Bronze Age mobile pastoralists of Central Eurasia

Archaeological research in Central Eurasia is exposing unprecedented scales of trans-regional interaction and technology transfer between East Asia and southwest Asia deep into the prehistoric past. This article presents a new archaeobotanical analysis from pastoralist campsites in the mountain and desert regions of Central Eurasia that documents the oldest known evidence for domesticated grains and farming among seasonally mobile herders. Carbonized grains from the sites of Tasbas and Begash illustrate the first transmission of southwest Asian and East Asian domesticated grains into the mountains of Inner Asia in the early third millennium BC. By the middle second millennium BC, seasonal camps in the mountains and deserts illustrate that Eurasian herders incorporated the cultivation of millet, wheat, barley and legumes into their subsistence strategy. These findings push back the chronology for domesticated plant use among Central Eurasian pastoralists by approximately 2000 years. Given the geography, chronology and seed morphology of these data, we argue that mobile pastoralists were key agents in the spread of crop repertoires and the transformation of agricultural economies across Asia from the third to the second millennium BC.     

Ca2+ and Mg2+ bind tetracycline with distinct stoichiometries and linked deprotonation

Tetracycline depends on divalent metal ions for its biological function, but its multiple ionization states, conformations, and tautomers at varying solution conditions complicate its ion-binding equilibria, and the stoichiometry of the biologically relevant Ca2+ or Mg2+ complexes has not been clear. Isothermal titration calorimetry was used in the present work to study Ca2+ and Mg2+ binding to tetracycline. The two metal ions bind with distinct stoichiometries, one Ca2+ per tetracycline and one Mg2+ per two tetracyclines, and with differing dependence on solution conditions, indicating that these two ions bind TC differently. An endothermic process accompanies ion binding that is proposed to reflect conformational changes in tetracycline. The results identify conditions that limit the distribution of species and may facilitate structural study.