Potassium channels selectively conduct K + ions across cellular membranes with extraordinary efficiency. Their selectivity filter exhibits four binding sites with approximately equal electron density in crystal structures with high K + concentrations, previously thought to reflect a superposition of alternating ion- and water-occupied states. Consequently, cotranslocation of ions with water has become a widely accepted ion conduction mechanism for potassium channels. By analyzing more than 1300 permeation events from molecular dynamics simulations at physiological voltages, we observed instead that permeation occurs via ion-ion contacts between neighboring K + ions. Coulomb repulsion between adjacent ions is found to be the key to high-efficiency K + conduction. Crystallographic data are consistent with directly neighboring K + ions in the selectivity filter, and our model offers an intuitive explanation for the high throughput rates of K + channels.

Specific arrestin conformations are coupled to distinct downstream effectors, which underlie the functions of many G-protein-coupled receptors (GPCRs). Here, using unnatural amino acid incorporation and fluorine-19 nuclear magnetic resonance (19F-NMR) spectroscopy, we demonstrate that distinct receptor phospho-barcodes are translated to specific β-arrestin-1 conformations and direct selective signalling. With its phosphate-binding concave surface, β-arrestin-1 ‘reads' the message in the receptor phospho-C-tails and distinct phospho-interaction patterns are revealed by 19F-NMR. Whereas all functional phosphopeptides interact with a common phosphate binding site and induce the movements of finger and middle loops, different phospho-interaction patterns induce distinct structural states of β-arrestin-1 that are coupled to distinct arrestin functions. Only clathrin recognizes and stabilizes GRK2-specific β-arrestin-1 conformations. The identified receptor-phospho-selective mechanism for arrestin conformation and the spacing of the multiple phosphate-binding sites in the arrestin enable arrestin to recognize plethora phosphorylation states of numerous GPCRs, contributing to the functional diversity of receptors.

Mechanosensitive ion channels convert mechanical stimuli into a flow of ions. These channels are widely distributed from bacteria to higher plants and humans, and are involved in many crucial physiological processes. Here we show that two members of the OSCA protein family in Arabidopsis thaliana, namely AtOSCA1.1 and AtOSCA3.1, belong to a new class of mechanosensitive ion channels. We solve the structure of the AtOSCA1.1 channel at 3.5-Å resolution and AtOSCA3.1 at 4.8-Å resolution by cryo-electron microscopy. OSCA channels are symmetric dimers that are mediated by cytosolic inter-subunit interactions. Strikingly, they have structural similarity to the mammalian TMEM16 family proteins. Our structural analysis accompanied with electrophysiological studies identifies the ion permeation pathway within each subunit and suggests a conformational change model for activation.

The microbial metabolic quotient (MMQ), microbial respiration per unit of biomass, is a fundamental factor controlling heterotrophic respiration, the largest carbon flux in soils. The magnitude and controls of MMQ at regional scale remain uncertain. We compiled a comprehensive data set of MMQ to investigate the global patterns and controls of MMQ in top 30 cm soils. Published MMQ values, generally measured in laboratory microcosms, were adjusted on ambient soil temperature using long‐term (30 yr) average site soil temperature and a Q10 = 2. The area‐weighted global average of MMQ_Soil is estimated as 1.8 (1.5–2.2) (95% confidence interval) μmol C·h−1·mmol−1 microbial biomass carbon (MBC) with substantial variations across biomes and between cropland and natural ecosystems. Variation was most closely associated with biological factors, followed by edaphic and meteorological parameters. MMQ_Soil was greatest in sandy clay and sandy clay loam and showed a pH maximum of 6.7 ± 0.1 (mean ± se). At large scale, MMQ_Soil varied with latitude and mean annual temperature (MAT), and was negatively correlated with microbial N:P ratio, supporting growth rate theory. These trends led to large differences in MMQ_Soil between natural ecosystems and cropland. When MMQ was adjusted to 11°C (MMQ_Ref), the global MAT in the top 30 cm of soils, the area‐weighted global averages of MMQ_Ref was 1.5 (1.3–1.8) μmol C·mmol MBC−1·h−1. The values, trends, and controls of MMQ_Soil add to our understanding of soil microbial influences on soil carbon cycling and could be used to represent microbial activity in global carbon models.

Multicellular organisms fight bacterial and fungal infections by producing peptide-derived broad-spectrum antibiotics. These hostdefense peptides compromise the integrity of microbial cell membranes and thus evade pathways by which bacteria develop rapid antibiotic resistance. Although more than 1,700 host-defense peptides have been identified, the structural and mechanistic basis of their action remains speculative. This impedes the desired rational development of these agents into next-generation antibiotics. We present the X-ray crystal structure as well as solid-state NMR spectroscopy, electrophysiology, and MD simulations of human dermcidin in membranes that reveal the antibiotic mechanism of this major human antimicrobial, found to suppress Staphylococcus aureus growth on the epidermal surface. Dermcidin forms an architecture of high-conductance transmembrane channels, composed of zinc-connected trimers of antiparallel helix pairs. Molecular dynamics simulations elucidate the unusual membrane permeation pathway for ions and show adjustment of the pore to various membranes. Our study unravels the comprehensive mechanism for the membrane-disruptive action of this mammalian host-defense peptide at atomistic level. The results may form a foundation for the structure-based design of peptide antibiotics.crystallography | electrophysiology | ion conduction | molecular dynamics

Marshes in the Sanjiang Plain of Northeast China have undergone dramatic loss and fragmentation over the past decades. This paper analyzed the loss and fragmentation of these marshes for the period 1954-2005 using historical land-cover information and remote sensing data. In 1954, marshes covered one-third of the total land area but have decreased by 77% over the 50 year period. Results showed two distinct periods of impact : 1954-1986 and 1987-2005. In the earlier period, the number of marsh patches fell from 4,799 to 1,476 (−69.2%), and total marsh area decreased from 35,270 km 2 to 13,893 km 2 (−60.6%). In the latter period, the number of marshes declined from 1,476 to 1,037 (−29.7%), and the total area decreased from 13,893 km 2 to 8,100 km 2 (−41.7%). The rapid decrease in the number and area of marshes during 1954-1986 was largely attributed to extensive agricultural reclamation under the "Food First" agricultural policy. This resulted in many negative ecological consequences. In contrast, the slower reduction of marsh areas during 1987-2005 was due to the implementation of governmental policies for protecting and restoring marshes. Increasing air temperature would otherwise have enhanced crop yields and stimulated the conversion of marsh into crops.

One key step in producing insulin-secreting cells from human embryonic stem (hES) cells is the generation of pancreatic and duodenal homeobox gene 1 (PDX1)-expressing pancreatic progenitor cells. All-trans retinoic acid (RA) has important roles in pancreas development and is widely used to induce pancreatic differentiation of ES cells. When RA was added directly to the activin A-induced hES cells, <20% cells were positive for the pancreatic marker PDX1, whereas the other cells were mainly hepatic cells. We found that when the activin A-induced hES cells were replated and seeded at low cell densities, the addition of RA induced significant pancreatic differentiation and over 70% of cells in culture expressed PDX1. When the endodermal cells were isolated with the surface marker CXCR4 from the activin A-induced culture and further differentiated with RA, a homogeneous PDX1(+) cell population (over 95% pure) was generated. The PDX1(+) cells could further differentiate into cells that expressed pancreatic transcription factors and pancreatic endocrine or exocrine markers. We also found that RA inhibited the hepatic differentiation of endodermal cells that were seeded at low cell densities, and this inhibition may have been through the inhibition of Smad1/5/8 activity. Thus, we present a highly efficient and reproducible protocol for generating PDX1(+) pancreatic progenitor cells from hES cells.

It has been well recognized that converting wetlands to cropland results in loss of soil organic carbon (SOC), while less attention was paid to concomitant changes in methane (CH 4 ) and nitrous oxide (N 2 O) emissions. Using datasets from the literature and field measurements, we investigated loss of SOC and emissions of CH 4 and N 2 O due to marshland conversion in northeast China. Analysis of the documented crop cultivation area indicated that 2.91 Mha of marshland were converted to cropland over the period 1950-2000. Marshland conversion resulted in SOC loss of $ 240 Tg and introduced $1.4 Tg CH 4 and $ 138 Gg N 2 O emissions in the cropland, while CH 4 emissions reduced greatly in the marshland, cumulatively $28 Tg over the 50 years. Taking into account the loss of SOC and emissions of CH 4 and N 2 O, the global warming potential (GWP) at a 20-year time horizon was estimated to be $ 180 Tg CO 2 _eq. yr À1 in the 1950s and $ 120 Tg CO 2 _eq. yr À1 in the 1990s, with a $ 33% reduction. When calculated at 100-year time horizon, the GWP was $ 73 Tg CO 2 _eq. yr À1 in the 1950s and $ 58 Tg CO 2 _eq. yr À1 in the 1990s, with a $ 21% reduction. It was concluded that marshland conversion to cropland in northeast China reduced the greenhouse effect as far as GWP is concerned. This reduction was attributed to a substantial decrease in CH 4 emissions from the marshland. An extended inference is that the declining growth rate of atmospheric CH 4 since the 1980s might be related to global loss of wetlands, but this connection needs to be confirmed.