Mechanism of Na+/H+ antiporting

Na+/H+ antiporters are central to cellular salt and pH homeostasis. The structure of Escherichia coli NhaA was recently determined, but its mechanisms of transport and pH regulation remain elusive. We performed molecular dynamics simulations of NhaA that, with existing experimental data, enabled us to propose an atomically detailed model of antiporter function. Three conserved aspartates are key to our proposed mechanism: Asp164 (D164) is the Na+-binding site, D163 controls the alternating accessibility of this binding site to the cytoplasm or periplasm, and D133 is crucial for pH regulation. Consistent with experimental stoichiometry, two protons are required to transport a single Na+ ion: D163 protonates to reveal the Na+-binding site to the periplasm, and subsequent protonation of D164 releases Na+. Additional mutagenesis experiments further validated the model.     

Fire and the nitrogen cycle in california chaparral

Analysis of soils from burned and unburned chaparral indicates that high nitrate concentrations following fire are due to the addition of ammonium and organic nitrogen in the ash. Inhibition of mineralization in unburned chaparral results in low nitrate concentrations. Fluctuations in the amount of soil nitrate in unburned chaparral are the direct result of foliar leaching.     

Ion binding by synthetic macrocyclic compounds

The existence of synthetic macrocyclic molecules with hydrophilic cavities containing multiple binding atoms and with hydrophobic exteriors gives rise to extraordinary possibilities with respect to the design and synthesis of molecules with specific cation and anion binding properties. The preparation of many new macrocyclic compounds has recently been reported, but few practical applications for them have been suggested. From the information available, it is becoming clear that it should be possible to synthesize macrocycles that will have specified, or selected, ion binding properties. Cavity size can be varied to accommodate only those cations or anions within a specified narrow band of sizes. Numbers and types of coordinating atoms can be chosen to give essentially electrostatic or covalent bonding or a combination of the two in a metalmacrocycle complex. The metal ligand bond appears to be predominantly ionic in the case of the cyclic polyethers but the covalent character increases on substitution of sulfur or nitrogen for oxygen donor atoms. The essential hydrophobic exteriors of the macrocycles can be modified by the addition of side chains and groups to facilitate the solution of anions and cations in organic solvents. The structures of many macrocycles can be made to approximate naturally occurring molecules, that is, cyclic polyethers similar to macrocyclic antibiotics of the valinomycin and nonactin types and cyclic polyamines similar to porphyrins. Macrocycles are also useful as model compounds for the study of metal interactions with biological systems. The synthetic macrocycles thus represent an intriguing new area of coordination chemistry, the systematic study of which should lead to many interesting and useful chemical applications in the field of metal complexation in solution.     

Discovery of olivine in the Nili Fssae region of Mars

We have detected a 30,000-square-kilometer area rich in olivine in the Nili Fossae region of Mars. Nili Fossae has been interpreted as a complex of grabens and fractures related to the formation of the Isidis impact basin. We propose that post-impact faulting of this area has exposed subsurface layers rich in olivine. Linear mixture analysis of Thermal Emission Spectrometer spectra shows surface exposures of 30% olivine, where the composition of the olivine ranges from Fo30 to Fo70.     

Shrinking Danish agriculture

Danish agriculture is facing a turning point. Centuries of struggle to increase arable land area as well as its productivity is about to be reversed, due to overproduction and environmental problems. Some land will probably be turned back to nature, and the use of chemicals in agriculture in general will be reduced, perhaps with a lower productivity and a better environment as a consequence. This paper mainly describes some of the political actions taken in Denmark to influence environmental-agricultural issues. First, however, some of the recently perceived environmental problems and over-production problems connected with Danish farming are outlined.     

Little evidence for developmental plasticity of adult hematopoietic stem cells

To rigorously test the in vivo cell fate specificity of bone marrow (BM) hematopoietic stem cells (HSCs), we generated chimeric animals by transplantation of a single green fluorescent protein (GFP)-marked HSC into lethally irradiated nontransgenic recipients. Single HSCs robustly reconstituted peripheral blood leukocytes in these animals, but did not contribute appreciably to nonhematopoietic tissues, including brain, kidney, gut, liver, and muscle. Similarly, in GFP+:GFP- parabiotic mice, we found substantial chimerism of hematopoietic but not nonhematopoietic cells. These data indicate that "transdifferentiation" of circulating HSCs and/or their progeny is an extremely rare event, if it occurs at all.     

MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling

The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments for lung cancers with EGFR activating mutations, but these tumors invariably develop drug resistance. Here, we describe a gefitinib-sensitive lung cancer cell line that developed resistance to gefitinib as a result of focal amplification of the MET proto-oncogene. inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 of 18 (22%) lung cancer specimens that had developed resistance to gefitinib or erlotinib. We find that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors. Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well.     

Below ground carbon turnover and greenhouse gas exchanges in a sub-arctic wetland

Here we present results from a field experiment in a sub-arctic wetland near Abisko, northern Sweden, where the permafrost is currently disintegrating with significant vegetation changes as a result. During one growing season we investigated the fluxes of CO₂ and CH₄ and how they were affected by ecosystem properties, i.e., composition of species that are currently expanding in the area (Carex rotundata, Eriophorum vaginatum and Eriophorum angustifolium), dissolved CH₄ in the pore water, substrate availability for methane producing bacteria, water table depth, active layer, temperature, etc. We found that the measured gas fluxes over the season ranged between: CH₄ 0.2 and 36.1 mg CH₄ m⁻² h⁻¹, Net Ecosystem Exchange (NEE) −1000 and 1250 mg CO₂ m⁻² h⁻¹ (negative values meaning a sink of atmospheric CO₂) and dark respiration 110 and 1700 mg CO₂ m⁻² h⁻¹. We found that NEE, photosynthetic rate and CH₄ emission were affected by the species composition. Multiple stepwise regressions indicated that the primary explanatory variables for NEE was photosynthetic rate and for respiration and photosynthesis biomass of green leaves. The primary explanatory variables for CH₄ emissions were depth of the water table, concentration of organic acid carbon and biomass of green leaves. The negative correlations between pore water concentration and emission of CH₄ and the concentrations of organic acid, amino acid and carbohydrate carbon indicated that these compounds or their fermentation by-products were substrates for CH₄ formation. Furthermore, calculation of the radiative forcing of the species expanding in the area as a direct result of permafrost degradation and a change in hydrology indicate that the studied mire may act as an increasing source of radiative forcing in future.