The product of the γ-secretase processing of ephrinB2 regulates VE-cadherin complexes and angiogenesis

Presenilin-1 (PS1) gene encodes the catalytic component of γ-secretase, which proteolytically processes several type I transmembrane proteins. We here present evidence that the cytosolic peptide efnB2/CTF2 produced by the PS1/γ-secretase cleavage of efnB2 ligand promotes EphB4 receptor-dependent angiogenesis in vitro. EfnB2/CTF2 increases endothelial cell sprouting and tube formation, stimulates the formation of angiogenic complexes that include VE-cadherin, Raf-1 and Rok-α, and increases MLC2 phosphorylation. These functions are mediated by the PDZ-binding domain of efnB2. Acute downregulation of PS1 or inhibition of γ-secretase inhibits the angiogenic functions of EphB4 while absence of PS1 decreases the VE-cadherin angiogenic complexes of mouse brain. Our data reveal a mechanism by which PS1/γ-secretase regulates efnB2/EphB4 mediated angiogenesis.     

Freiberg and the Frontier: Louis Janin,German Engineering,and ‘Civilisation’ in the American West

Mining companies after the Gold Rush depended heavily on foreign expertise, and yet historians of mining have glorified ‘German engineering’ in America. The application of German technology in America was fraught with difficulties, and most advances were micro- rather than macro-innovations, such as Philip Deidesheimer's famous square-set timbering on the Comstock Lode. The problem began at German mining schools, such as the Freiberg Mining Academy, where Americans like Louis and Henry Janin, while they acquired advanced training and adopted an engineering ethos, struggled to learn about Mexican and American mining. Having complemented their course of study to remedy this deficiency, the brothers returned to the US intending to modernize mining on the frontier. Louis attempted the ‘Freiberg Process’ of amalgamation on the Comstock Lode, but locally developed methods proved more feasible, and the experiment failed. He came to apply his training rather toward the micro-level problem of how to reprocess amalgamation waste heaps.     

Characteristics of swift fox dens in northwest Texas

The swift fox ( Vulpes velox ) was classified in 1995 as a candidate for listing under the Endangered Species Act. Since then, several studies have addressed survey methods for monitoring swift fox populations. The purpose of this paper is to assist field researchers in documenting the presence of swift foxes by identification of recently active den sites. We propose that swift foxes have unique external den characteristics that can be distinguished during aerial surveys. We collected data from 30 swift fox den complexes on both continuous rangeland and landscapes fragmented by cropland in northwest Texas. There were no differences in den characteristics between landscape types ( P > 0.10). The number of openings per den ranged from 1 to 8 and had an average opening height of 20 cm. As number of openings increased, the maximum distance between openings also increased ( r = 0.88, P Canis latrans ) and red foxes ( Vulpes vulpes ), 2 species that can be sympatric with swift foxes. We suggest that aerial den searching followed by ground verification may be an effective technique for determining presence of swift foxes in areas of short-grass prairies and fragmented habitats.     

Variation in leaf anatomy and CO 2 assimilation in Sitanion hystrix ecotypes

Collections of Sitanion hystrix known to differ in phenological development, height, dry matter production, and total water use were examined for possible differences in leaf anatomy and in CO 2 assimilation rates. Collections originating in warm, dry habitats produced the narrowest leaves with the fewest veins. Other anatomical characteristics examined were either not different among collections or the differences did not appear to be related to the original habitats. The CO 2 assimilation rates were similar on per-unit weight basis; therefore total assimilation varied as a function of plant size.     

Disturbance of lekking Lesser Prairie-Chickens ( Tympanuchus pallidicinctus ) by Ring-necked Pheasants ( Phasianus colchicus )

Lesser Prairie-Chicken ( Tympanuchus pallidicinctus ) populations have experienced dramatic rangewide declines (up to 92%) since settlement of the Great Plains. This decline has been attributed to changes in land-use practices, such as conversion of native rangelands to intensive agriculture and increased grazing pressure. These changes may increase the impact of interspecific competition on populations. We documented disturbance of lekking Lesser Prairie-Chickens by Ring-necked Pheasants ( Phasianus colchicus ). Future management and research should take into account possible impacts to Lesser Prairie-Chickens during the breeding season.     

T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance

Furin is one of seven proprotein convertase family members that promote proteolytic maturation of proproteins. It is induced in activated T cells and is reported to process a variety of substrates including the anti-inflammatory cytokine transforming growth factor (TGF)-beta1 (refs 2-4), but the non-redundant functions of furin versus other proprotein convertases in T cells are unclear. Here we show that conditional deletion of furin in T cells allowed for normal T-cell development but impaired the function of regulatory and effector T cells, which produced less TGF-beta1. Furin-deficient T regulatory (Treg) cells were less protective in a T-cell transfer colitis model and failed to induce Foxp3 in normal T cells. Additionally, furin-deficient effector cells were inherently over-active and were resistant to suppressive activity of wild-type Treg cells. Thus, our results indicate that furin is indispensable in maintaining peripheral tolerance, which is due, at least in part, to its non-redundant, essential function in regulating TGF-beta1 production. Targeting furin has emerged as a strategy in malignant and infectious disease. Our results suggest that inhibiting furin might activate immune responses, but may result in a breakdown in peripheral tolerance.     

Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes

The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200-300 million years. The human MSY (male-specific region of Y chromosome) retains only three percent of the ancestral autosomes' genes owing to genetic decay. This evolutionary decay was driven by a series of five 'stratification' events. Each event suppressed X-Y crossing over within a chromosome segment or 'stratum', incorporated that segment into the MSY and subjected its genes to the erosive forces that attend the absence of crossing over. The last of these events occurred 30 million years ago, 5 million years before the human and Old World monkey lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome, remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the Old World monkey lineage. To investigate this question, we sequenced the MSY of the rhesus macaque, an Old World monkey, and compared it to the human MSY. We discovered that during the last 25 million years MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. In the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 million years ago. Likewise, the rhesus MSY has not lost any older genes (from strata 1-4) during the past 25 million years, despite its major structural differences to the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection.     

Designer Dirac fermions and topological phases in molecular graphene

The observation of massless Dirac fermions in monolayer graphene has generated a new area of science and technology seeking to harness charge carriers that behave relativistically within solid-state materials. Both massless and massive Dirac fermions have been studied and proposed in a growing class of Dirac materials that includes bilayer graphene, surface states of topological insulators and iron-based high-temperature superconductors. Because the accessibility of this physics is predicated on the synthesis of new materials, the quest for Dirac quasi-particles has expanded to artificial systems such as lattices comprising ultracold atoms. Here we report the emergence of Dirac fermions in a fully tunable condensed-matter system-molecular graphene-assembled by atomic manipulation of carbon monoxide molecules over a conventional two-dimensional electron system at a copper surface. Using low-temperature scanning tunnelling microscopy and spectroscopy, we embed the symmetries underlying the two-dimensional Dirac equation into electron lattices, and then visualize and shape the resulting ground states. These experiments show the existence within the system of linearly dispersing, massless quasi-particles accompanied by a density of states characteristic of graphene. We then tune the quantum tunnelling between lattice sites locally to adjust the phase accrual of propagating electrons. Spatial texturing of lattice distortions produces atomically sharp p-n and p-n-p junction devices with two-dimensional control of Dirac fermion density and the power to endow Dirac particles with mass. Moreover, we apply scalar and vector potentials locally and globally to engender topologically distinct ground states and, ultimately, embedded gauge fields, wherein Dirac electrons react to 'pseudo' electric and magnetic fields present in their reference frame but absent from the laboratory frame. We demonstrate that Landau levels created by these gauge fields can be taken to the relativistic magnetic quantum limit, which has so far been inaccessible in natural graphene. Molecular graphene provides a versatile means of synthesizing exotic topological electronic phases in condensed matter using tailored nanostructures.