Dependence of EPSP efficacy on synapse location in neocortical pyramidal neurons

Neurons receive thousands of synaptic inputs throughout elaborate dendritic trees. Here we determine the somatic impact of excitatory postsynaptic potentials (EPSPs) generated at known dendritic sites in neocortical pyramidal neurons. As inputs became more distal, somatic EPSP amplitude decreased, whereas use-dependent depression increased. Despite marked attenuation (>40-fold), when coactivated within a narrow time window (approximately 10 milliseconds), distal EPSPs could directly influence action potential output following dendritic spike generation. These findings reveal that distal EPSPs are ineffective sources of background somatic excitation, but through coincidence detection have a powerful transient signaling role.     

Comparison of spatially explicit forest landscape fire disturbance models

Comparisons of model behaviors are an efficient way of understanding the differences amongst various models and thus providing guidance to model users for selecting suitable models for their own purposes. This study focuses on a comparison of the most commonly used fire spread algorithms used in scenario fire regime models. This paper provides an overview of fire regime modeling and describes a simulation model, Ecological Disturbance Model, as a simulation shell for such a comparison using the Fort A La Corne forest area in central Saskatchewan, Canada, as the study area. Simulation results suggested that for a fire scenario modeling approach, various fire spread algorithms such as DISPATCH, percolation, and cellular automata (CA) may not result in significant differences between user-defined and simulated fire frequencies; however, significant differences in simulated forest dynamics could result when using different fire spread algorithms. The simulation results from DISPATCH and CA are more similar than those from the percolation algorithm; however, the latter appeared to be a better representative of observed fire spread processes due to its underlying assumption of fire spread mechanisms. Simulation results also suggested that the fire spread algorithms that replicate four or eight direction fire spread in percolation and CA will not make a significant difference in simulated fire regimes or forest dynamics. It is thus recommend that using simulation shells as a tool to take alternative assumptions or models into account to narrow down the uncertainty parameters and avoid the paradoxes in the modeling of natural resource management.     

Mutational analysis of the tyrosine phosphatome in colorectal cancers

Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations were nonsense, frameshift, or splice-site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRT) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the mutated tyrosine phosphatases are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.     

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.     

Origin and evolution of prebiotic organic matter as inferred from the Tagish Lake meteorite

The complex suite of organic materials in carbonaceous chondrite meteorites probably originally formed in the interstellar medium and/or the solar protoplanetary disk, but was subsequently modified in the meteorites' asteroidal parent bodies. The mechanisms of formation and modification are still very poorly understood. We carried out a systematic study of variations in the mineralogy, petrology, and soluble and insoluble organic matter in distinct fragments of the Tagish Lake meteorite. The variations correlate with indicators of parent body aqueous alteration. At least some molecules of prebiotic importance formed during the alteration.     

Trench-parallel anisotropy produced by foundering of arc lower crust

Many volcanic arcs display fast seismic shear-wave velocities parallel to the strike of the trench. This pattern of anisotropy is inconsistent with simple models of corner flow in the mantle wedge. Although several models, including slab rollback, oblique subduction, and deformation of water-rich olivine, have been proposed to explain trench-parallel anisotropy, none of these mechanisms are consistent with all observations. Instead, small-scale convection driven by the foundering of dense arc lower crust provides an explanation for the trench-parallel anisotropy, even in settings with orthogonal convergence and no slab rollback.     

Dynamics of mammalian chromosome evolution inferred from multispecies comparative maps

The genome organizations of eight phylogenetically distinct species from five mammalian orders were compared in order to address fundamental questions relating to mammalian chromosomal evolution. Rates of chromosome evolution within mammalian orders were found to increase since the Cretaceous-Tertiary boundary. Nearly 20% of chromosome breakpoint regions were reused during mammalian evolution; these reuse sites are also enriched for centromeres. Analysis of gene content in and around evolutionary breakpoint regions revealed increased gene density relative to the genome-wide average. We found that segmental duplications populate the majority of primate-specific breakpoints and often flank inverted chromosome segments, implicating their role in chromosomal rearrangement.