Topography of the northern hemisphere of Mercury from MESSENGER laser altimetry

Laser altimetry by the MESSENGER spacecraft has yielded a topographic model of the northern hemisphere of Mercury. The dynamic range of elevations is considerably smaller than those of Mars or the Moon. The most prominent feature is an extensive lowland at high northern latitudes that hosts the volcanic northern plains. Within this lowland is a broad topographic rise that experienced uplift after plains emplacement. The interior of the 1500-km-diameter Caloris impact basin has been modified so that part of the basin floor now stands higher than the rim. The elevated portion of the floor of Caloris appears to be part of a quasi-linear rise that extends for approximately half the planetary circumference at mid-latitudes. Collectively, these features imply that long-wavelength changes to Mercury's topography occurred after the earliest phases of the planet's geological history.     

Crystal structure of a lipid G protein-coupled receptor

The lyso-phospholipid sphingosine 1-phosphate modulates lymphocyte trafficking, endothelial development and integrity, heart rate, and vascular tone and maturation by activating G protein-coupled sphingosine 1-phosphate receptors. Here, we present the crystal structure of the sphingosine 1-phosphate receptor 1 fused to T4-lysozyme (S1P(1)-T4L) in complex with an antagonist sphingolipid mimic. Extracellular access to the binding pocket is occluded by the amino terminus and extracellular loops of the receptor. Access is gained by ligands entering laterally between helices I and VII within the transmembrane region of the receptor. This structure, along with mutagenesis, agonist structure-activity relationship data, and modeling, provides a detailed view of the molecular recognition and requirement for hydrophobic volume that activates S1P(1), resulting in the modulation of immune and stromal cell responses.     

A systematic survey of loss-of-function variants in human protein-coding genes

Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2951 putative LoF variants obtained from 185 human genomes to determine their true prevalence and properties. We estimate that human genomes typically contain ~100 genuine LoF variants with ~20 genes completely inactivated. We identify rare and likely deleterious LoF alleles, including 26 known and 21 predicted severe disease-causing variants, as well as common LoF variants in nonessential genes. We describe functional and evolutionary differences between LoF-tolerant and recessive disease genes and a method for using these differences to prioritize candidate genes found in clinical sequencing studies.     

Structure–activity relationships of eugenol derivatives against Aedes aegypti (Diptera: Culicidae) larvae

BACKGROUND: Dengue fever is a severe public health problem for several countries. In order to find effective larvicides to aid control programs, the structure‐activity relationships of eugenol derivatives against Aedes aegypti (Diptera: Culicidae) larvae were evaluated. Additionally, the composition and larvicidal activity of Syzygium aromaticum essential oil was assessed. RESULTS: Four compounds representing 99.05% of S. aromaticum essential oil have been identified. The essential oil was active against Ae. aegypti larvae (LC₅₀ = 62.3 and 77.0 ppm, field‐collected and Rockefeller larvae respectively). The larvicidal activity of eugenol, the major compound of the essential oil, was further evaluated (LC₅₀ = 93.3 and 71.9 ppm, field‐collected and Rockefeller larvae respectively). The larvicidal activity and structure‐activity relationships of synthetic derivatives of eugenol were also assessed. The larvicidal activity of the derivatives varied between 62.3 and 1614.9 ppm. Oxidation of eugenol allylic bond to a primary alcohol and removal of the phenolic proton resulted in decreased potency. However, oxidation of the same double bond in 1‐benzoate‐2‐methoxy‐4‐(2‐propen‐1‐yl)‐phenol resulted in increased potency. CONCLUSION: Structural characteristics were identified that may contribute to the understanding of the larvicidal activity of phenylpropanoids. The present approach may help future work in the search for larvicidal compounds. Copyright © 2012 Society of Chemical Industry     

Use of a potentiometric vital dye to determine the effect of the herbicide bromoxynil octanoate on mitochondrial bioenenergetics in Chlamydomonas reinhardtii

BACKGROUND: The aims of the present study were to validate a vital mitochondrial potentiometric staining method in Chlamydomonas reinhardtii and to utilise this method to examine the effect of the herbicide bromoxynil octanoate on mitochondrial potential in this species. A range of stains was investigated, including Rhodamine 123, DASPMI, Mitotracker Green, Mitotracker Orange and JC‐1. RESULTS: Rhodamine 123 (R123) had the highest utility of several candidate stains. Incubation with both 5 and 10 µM carbonyl cyanide 3‐chlorophenylhydrazone caused significant fluorescence collapse [Dunn's post test (40.00, P < 0.01) and (45.49, P < 0.01) respectively], demonstrating that the R123 fluorescence reported mitochondrial potential. The effect of the herbicide bromoxynil octanoate was examined. Exposure to 0.1 mM of bromoxynil resulted in a significant increased mitochondrial fluorescence compared with the baseline (Mann–Whitney U = 222, P < 0.002), while concentrations of 1 mM and greater resulted in significant, almost complete loss of mitochondrial potential [mean fluorescence ratio = 1.193–1.289 (where a ratio of 1 represents total potential loss), Mann–Whitney U = 0.0, P < 0.001 (1 mM ), 0.0, P < 0.0001 (2 mM ), 0.0, P < 0.0001 (5 mM )]. EC₅₀ of the collapse in mitochondrial potential owing to bromoxynil incubation occurred at 0.72 mM , and the mean t₅₀ of bromoxynil octanoate action was 93 s. CONCLUSIONS: R123 is a sensitive potentiometric dye in C. reinhardtii that may find further use in investigations of both mitochondrial bioenergetics in plants and environmental toxicology. Copyright © 2011 Society of Chemical Industry     

PrP antibodies do not trigger mouse hippocampal neuron apoptosis

Intraperitoneal administration of ICSM18 and 35, monoclonal antibodies against prion protein (PrP), has been shown to significantly delay the onset of prion disease in mice, and humanized versions are candidate therapeutics for prion and Alzheimer's diseases. However, a previous report of severe and widespread apoptosis after intracerebral injection of anti-PrP monoclonal antibodies raised concerns about such therapy and led to an influential model of prion neurotoxicity via cross-linking of cell surface PrP by disease-related PrP aggregates. In extensive studies including ICSM18 and 35, fully humanized ICSM18, and the previously reported proapoptotic antibodies, we found no evidence of apoptosis, thereby questioning this model of prion neurotoxicity.     

Dislocation damping and anisotropic seismic wave attenuation in Earth's upper mantle

Crystal defects form during tectonic deformation and are reactivated by the shear stress associated with passing seismic waves. Although these defects, known as dislocations, potentially contribute to the attenuation of seismic waves in Earth's upper mantle, evidence for dislocation damping from laboratory studies has been circumstantial. We experimentally determined the shear modulus and associated strain-energy dissipation in pre-deformed synthetic olivine aggregates under high pressures and temperatures. Enhanced high-temperature background dissipation occurred in specimens pre-deformed by dislocation creep in either compression or torsion, the enhancement being greater for prior deformation in torsion. These observations suggest the possibility of anisotropic attenuation in relatively coarse-grained rocks where olivine is or was deformed at relatively high stress by dislocation creep in Earth's upper mantle.