Cortical axon guidance by the glial wedge during the development of the corpus callosum

Growing axons are often guided to their final destination by intermediate targets. In the developing spinal cord and optic nerve, specialized cells at the embryonic midline act as intermediate targets for guiding commissural axons. Here we investigate whether similar intermediate targets may play a role in guiding cortical axons in the developing brain. During the development of the corpus callosum, cortical axons from one cerebral hemisphere cross the midline to reach their targets in the opposite cortical hemisphere. We have identified two early differentiating populations of midline glial cells that may act as intermediate guideposts for callosal axons. The first differentiates directly below the corpus callosum forming a wedge shaped structure (the glial wedge) and the second differentiates directly above the corpus callosum within the indusium griseum. Axons of the corpus callosum avoid both of these populations in vivo. This finding is recapitulated in vitro in three-dimensional collagen gels. In addition, experimental manipulations in organotypic slices show that callosal axons require the presence and correct orientation of these populations to turn toward the midline. We have also identified one possible candidate for this activity because both glial populations express the chemorepellent molecule slit-2, and cortical axons express the slit-2 receptors robo-1 and robo-2. Furthermore, slit-2 repels-suppresses cortical axon growth in three-dimensional collagen gel cocultures

Local adaptation drives the diversification of effectors in the fungal wheat pathogen Parastagonospora nodorum in the United States

Filamentous fungi rapidly evolve in response to environmental selection pressures in part due to their genomic plasticity. Parastagonospora nodorum, a fungal pathogen of wheat and causal agent of septoria nodorum blotch, responds to selection pressure exerted by its host, influencing the gain, loss, or functional diversification of virulence determinants, known as effector genes. Whole genome resequencing of 197 P. nodorum isolates collected from spring, durum, and winter wheat production regions of the United States enabled the examination of effector diversity and genomic regions under selection specific to geographically discrete populations. 1,026,859 SNPs/InDels were used to identify novel loci, as well as SnToxA and SnTox3 as factors in disease. Genes displaying presence/absence variation, predicted effector genes, and genes localized on an accessory chromosome had significantly higher pN/pS ratios, indicating a higher rate of sequence evolution. Population structure analyses indicated two P. nodorum populations corresponding to the Upper Midwest (Population 1) and Southern/Eastern United States (Population 2). Prevalence of SnToxA varied greatly between the two populations which correlated with presence of the host sensitivity gene Tsn1 in the most prevalent cultivars in the corresponding regions. Additionally, 12 and 5 candidate effector genes were observed to be under diversifying selection among isolates from Population 1 and 2, respectively, but under purifying selection or neutrally evolving in the opposite population. Selective sweep analysis revealed 10 and 19 regions that had recently undergone positive selection in Population 1 and 2, respectively, involving 92 genes in total. When comparing genes with and without presence/absence variation, those genes exhibiting this variation were significantly closer to transposable elements. Taken together, these results indicate that P. nodorum is rapidly adapting to distinct selection pressures unique to spring and winter wheat production regions by rapid adaptive evolution and various routes of genomic diversification, potentially facilitated through transposable element activity

Slit2 guides both precrossing and postcrossing callosal axons at the midline in vivo

Commissural axons generally cross the midline only once. In the Drosophila nerve cord and mouse spinal cord, commissural axons are guided by Slit only after they cross the midline, where Slit prevents these axons from recrossing the midline. In the developing corpus callosum, Slit2 expressed by the glial wedge guides callosal axons before they cross the midline, as they approach the corticoseptal boundary. These data highlighted a potential difference between the role of Slit2 in guiding commissural axons in the brain compared with the spinal cord. Here, we investigate whether Slit2 also guides callosal axons after they cross the midline. Because such questions cannot be addressed in conventional gene knock-out animals, we used in utero injections of antisense oligonucleotides to specifically deplete Slit2 on only one side of the brain. We used this technique together with a novel in vitro assay of hemisected brain slices to specifically analyze postcrossing callosal axons. We find that in the brain, unlike the spinal cord, Slit2 mediates both precrossing and postcrossing axonal guidance. Depletion of Slit2 on one side of the brain causes axons to defasciculate and, in some cases, to aberrantly enter the septum. Because these axons do not recross the midline, we conclude that the principle function of Slit2 at the cortical midline maybe to channel the axons along the correct path and possibly repel them away from the midline. We find no evidence that Slit2 prevents axons from recrossing the midline in the brain

Aperiodic invariant continua for surface homeomorphisms

We prove that if a homeomorphism of a closed orientable surface S has no wandering points and leaves invariant a compact, connected set K which contains no periodic points, then either K=S and S is a torus, or $K$ is the intersection of a decreasing sequence of annuli. A version for non-orientable surfaces is given.Comment: 8 pages, to appear in Mathematische Zeitschrif

Management of anticoagulant-refractory thrombotic antiphospholipid syndrome

Lifelong anticoagulation with warfarin or alternative vitamin K antagonist is the standard anticoagulant treatment for thrombotic antiphospholipid syndrome. Anticoagulant-refractory thrombotic antiphospholipid syndrome can be broadly defined as breakthrough thrombosis while on standard oral anticoagulation treatment and its management is a major challenge given the serious nature of the thrombotic disease observed, which has become refractory to oral anticoagulation. The factors (genetic and cellular) that cause anticoagulant-refractory thrombotic antiphospholipid syndrome are now better understood. However, efforts to use this greater understanding have not yet transformed the capacity to treat it successfully in many patients. In this Viewpoint, we review the factors that are likely to be contributing to the cause of this syndrome and consider how they might be modified or inhibited. We also discuss management, including general strategies to minimise thrombotic risk, intensification of anticoagulation, addition of an antiplatelet agent, adjunctive treatment for thrombosis, immunomodulatory therapy, complement inhibition, vascular options, and future potential therapeutic targets

Shrub-interspace dynamics alter relationships between microbial community composition and belowground ecosystem characteristics

In desert ecosystems, belowground characteristics are influenced chiefly by the formation and persistence of “shrub-islands of fertility” in contrast to barren plant interspaces. If soil microbial communities are exclusively compared between these two biogeochemically distinct soil types, the impact of characteristics altered by shrub species, especially soil C and N, are likely to be overemphasized and overshadow the role of other characteristics in structuring microbial composition. To determine how belowground characteristics influence microbial community composition, and if the relative importance of these characteristics shifts across the landscape (i.e., between and within shrub and interspace soils), changes in microbial communities across a 3000-year cold desert chronosequence were related to 27 belowground characteristics in surface and subsurface soils. When shrub and interspace communities in surface and subsurface soils were combined across the entire chronosequence, communities differed and were primarily influenced by soil C, NO3− concentrations, bulk density, pH, and root presence. Within shrub soils, microbial communities were shrub species-specific, especially in surface soils, highlighting differences in soil characteristics created by specific shrub species and/or similarity in stresses structuring shrub species and microbial communities alike. Microbial communities in shrub soils were not influenced by soil C, but by NO3− and NH4+ concentrations, pH, and silt in surface soils; and Cl, P, soil N, and NO3−concentrations in subsurface soils. Interspace soil communities were distinct across the chronosequence at both depths and were strongly influenced by dune development. Interspace communities were primarily associated with soil stresses (i.e., high B and Cl concentrations), which decreased with dune development. The distribution of Gram-positive bacteria, Actinobacteria, and fungi highlighted community differences between and within shrub and interspace soils, while Gram-negative bacteria were common in all soils across the chronosequence. Of the 27 belowground characteristics investigated, 13 separated shrub from interspace communities, and of those, only five emerged as factors influencing community composition within shrub and interspace soils. As dunes develop across this cold desert chronosequence, microbial community composition was not regulated primarily by soil C, but by N and P availability and soil stresses in shrub soils, and exclusively by soil stresses in interspace soils

Continental-Scale Soil Organic Carbon Composition and Vulnerability Regulated by Regional Soil and Environmental Controls

Processes that control soil organic carbon (C) composition and dynamics over large scales are not well understood. Thus, our understanding of C cycling is incomplete, making it difficult to predict C gains and losses due to changes in climate, land use and management. In this paper, we show that controls on the composition of organic C, the particulate, humus (or mineral associated) and resistant fractions, and the potential vulnerability of C to decomposition across Australia are distinct, scale-dependent and variable

The flow of plasma in the solar terrestrial environment

The overall goal of our NASA Theory Program was to study the coupling, time delays, and feedback mechanisms between the various regions of the solar-terrestrial system in a self-consistent, quantitative manner. To accomplish this goal, it will eventually be necessary to have time-dependent macroscopic models of the different regions of the solar-terrestrial system and we are continually working toward this goal. However, with the funding from this NASA program, we concentrated on the near-earth plasma environment, including the ionosphere, the plasmasphere, and the polar wind. In this area, we developed unique global models that allowed us to study the coupling between the different regions. These results are highlighted in the next section. Another important aspect of our NASA Theory Program concerned the effect that localized 'structure' had on the macroscopic flow in the ionosphere, plasmasphere, thermosphere, and polar wind. The localized structure can be created by structured magnetospheric inputs (i.e., structured plasma convection, particle precipitation or Birkland current patterns) or time variations in these input due to storms and substorms. Also, some of the plasma flows that we predicted with our macroscopic models could be unstable, and another one of our goals was to examine the stability of our predicted flows. Because time-dependent, three-dimensional numerical models of the solar-terrestrial environment generally require extensive computer resources, they are usually based on relatively simple mathematical formulations (i.e., simple MHD or hydrodynamic formulations). Therefore, another goal of our NASA Theory Program was to study the conditions under which various mathematical formulations can be applied to specific solar-terrestrial regions. This could involve a detailed comparison of kinetic, semi-kinetic, and hydrodynamic predictions for a given polar wind scenario or it could involve the comparison of a small-scale particle-in-cell (PIC) simulation of a plasma expansion event with a similar macroscopic expansion event. The different mathematical formulations have different strengths and weaknesses and a careful comparison of model predictions for similar geophysical situations provides insight into when the various models can be used with confidence