Simultaneous targeting of Eph receptors in glioblastoma

Eph tyrosine kinase receptors are frequently overexpressed and functional in many cancers, and they are attractive candidates for targeted therapy. Here, we analyzed the expression of Eph receptor A3, one of the most up-regulated factors in glioblastoma cells cultured under tumorsphere-forming conditions, together with EphA2 and EphB2 receptors. EphA3 was overexpressed in up to 60% of glioblastoma tumors tested, but not in normal brain. EphA3 was localized in scattered areas of the tumor, the invasive ring, and niches near tumor vessels. EphA3 co-localized with macrophage/leukocyte markers, suggesting EphA3 expression on tumor-infiltrating cells of bone marrow origin. We took advantage of the fact that ephrinA5 (eA5) is a ligand that binds EphA3, EphA2 and EphB2 receptors, and used it to construct a novel targeted anti-glioblastoma cytotoxin. The eA5-based cytotoxin potently and specifically killed glioblastoma cells with an IC(50) of at least 10(−11) M. This and similar cytotoxins will simultaneously target different compartments of glioblastoma tumors while mitigating tumor heterogeneity

Biodiversity Loss and the Taxonomic Bottleneck: Emerging Biodiversity Science

Human domination of the Earth has resulted in dramatic changes to global and local patterns of biodiversity. Biodiversity is critical to human sustainability because it drives the ecosystem services that provide the core of our life-support system. As we, the human species, are the primary factor leading to the decline in biodiversity, we need detailed information about the biodiversity and species composition of specific locations in order to understand how different species contribute to ecosystem services and how humans can sustainably conserve and manage biodiversity. Taxonomy and ecology, two fundamental sciences that generate the knowledge about biodiversity, are associated with a number of limitations that prevent them from providing the information needed to fully understand the relevance of biodiversity in its entirety for human sustainability: (1) biodiversity conservation strategies that tend to be overly focused on research and policy on a global scale with little impact on local biodiversity; (2) the small knowledge base of extant global biodiversity; (3) a lack of much-needed site-specific data on the species composition of communities in human-dominated landscapes, which hinders ecosystem management and biodiversity conservation; (4) biodiversity studies with a lack of taxonomic precision; (5) a lack of taxonomic expertise and trained taxonomists; (6) a taxonomic bottleneck in biodiversity inventory and assessment; and (7) neglect of taxonomic resources and a lack of taxonomic service infrastructure for biodiversity science. These limitations are directly related to contemporary trends in research, conservation strategies, environmental stewardship, environmental education, sustainable development, and local site-specific conservation. Today’s biological knowledge is built on the known global biodiversity, which represents barely 20% of what is currently extant (commonly accepted estimate of 10 million species) on planet Earth. Much remains unexplored and unknown, particularly in hotspots regions of Africa, South Eastern Asia, and South and Central America, including many developing or underdeveloped countries, where localized biodiversity is scarcely studied or described. ‘‘Backyard biodiversity’’, defined as local biodiversity near human habitation, refers to the natural resources and capital for ecosystem services at the grassroots level, which urgently needs to be explored, documented, and conserved as it is the backbone of sustainable economic development in these countries. Beginning with early identification and documentation of local flora and fauna, taxonomy has documented global biodiversity and natural history based on the collection of ‘‘backyard biodiversity’’ specimens worldwide. However, this branch of science suffered a continuous decline in the latter half of the twentieth century, and has now reached a point of potential demise. At present there are very few professional taxonomists and trained local parataxonomists worldwide, while the need for, and demands on, taxonomic services by conservation and resource management communities are rapidly increasing. Systematic collections, the material basis of biodiversity information, have been neglected and abandoned, particularly at institutions of higher learning. Considering the rapid increase in the human population and urbanization, human sustainability requires new conceptual and practical approaches to refocusing and energizing the study of the biodiversity that is the core of natural resources for sustainable development and biotic capital for sustaining our life-support system. In this paper we aim to document and extrapolate the essence of biodiversity, discuss the state and nature of taxonomic demise, the trends of recent biodiversity studies, and suggest reasonable approaches to a biodiversity science to facilitate the expansion of global biodiversity knowledge and to create useful data on backyard biodiversity worldwide towards human sustainability

Emergent Properties of Patch Shapes Affect Edge Permeability to Animals

Animal travel between habitat patches affects populations, communities and ecosystems. There are three levels of organization of edge properties, and each of these can affect animals. At the lowest level are the different habitats on each side of an edge, then there is the edge itself, and finally, at the highest level of organization, is the geometry or structure of the edge. This study used computer simulations to (1) find out whether effects of edge shapes on animal behavior can arise as emergent properties solely due to reactions to edges in general, without the animals reacting to the shapes of the edges, and to (2) generate predictions to allow field and experimental studies to test mechanisms of edge shape response. Individual animals were modeled traveling inside a habitat patch that had different kinds of edge shapes (convex, concave and straight). When animals responded edges of patches, this created an emergent property of responding to the shape of the edge. The response was mostly to absolute width of the shapes, and not the narrowness of them. When animals were attracted to edges, then they tended to collect in convexities and disperse from concavities, and the opposite happened when animals avoided edges. Most of the responses occurred within a distance of 40% of the perceptual range from the tip of the shapes. Predictions were produced for directionality at various locations and combinations of treatments, to be used for testing edge behavior mechanisms. These results suggest that edge shapes tend to either concentrate or disperse animals, simply because the animals are either attracted to or avoid edges, with an effect as great as 3 times the normal density. Thus edge shape could affect processes like pollination, seed predation and dispersal and predator abundance

Indirect effects of species interactions on habitat provisioning

Species that shelter in a biogenic habitat can influence their refugia and, in turn, play an essential role in shaping local patterns of biodiversity. Here we explore a positive feedback loop between the provisioning rate of habitat-forming branching corals and their associated fishes and show how interactions between two groups of fish—the planktivorous damselfish and predatory hawkfish—altered the feedback. A field experiment confirmed that skeletal growth of branching coral (genus Pocillopora) increased substantially with increasing numbers (biomass) of resident fishes, likely because they greatly increased the interstitial concentrations of nutrients. Because there is a positive relationship between colony size and number (biomass) of associated fishes (primarily damselfishes in the Family Pomacentridae), a structure–function feedback loop exists in which increasing numbers of damselfish enhance coral growth and larger corals host greater abundances (and species richness) of fish. However, interactions between damselfishes and arc-eye hawkfish, Paracirrhites arcatus, a largely solitary resident, can disrupt this positive feedback loop. Field surveys revealed a marked pattern of fish occupancy related to coral size: Pocillopora colonies of sufficient size to host fish (>40 cm circumference) had either groups of damselfish or an arc-eye hawkfish; only larger colonies (>75 cm) were occupied by both the damselfish and hawkfish. Subsequent short- and long-term experiments revealed that on intermediate-sized Pocillopora colonies, arc-eye hawkfish prevented the establishment of damselfish by suppressing their recruitment. The demographic consequences to the host coral were substantial; in a 1-year-long experiment, intermediate-size Pocillopora occupied by hawkfish grew at half the rate of corals that hosted groups of damselfish. These findings indicate that: (1) species which occupy a biogenic habitat can enhance the provisioning rate of their habitat; (2) such positive feedbacks between community structure and ecosystem function can be disrupted by a strong interactor; (3) even substantial consequences on ecosystem processes that arise can be difficult to discern

Extinction Debt in Source-Sink Metacommunities

In an increasingly modified world, understanding and predicting the consequences of landscape alteration on biodiversity is a challenge for ecologists. To this end, metacommunity theory has developed to better understand the complexity of local and regional interactions that occur across larger landscapes. While metacommunity ecology has now provided several alternative models of species coexistence at different spatial scales, predictions regarding the consequences of landscape alteration have been done exclusively for the competition-colonization trade off model (CC). In this paper we investigate the effects of landscape perturbation on source-sink metacommunities. We show that habitat destruction perturbs the equilibria among species competitive effects within the metacommunity, driving both direct extinctions and an indirect extinction debt. As in CC models, we found a time lag for extinction following habitat destruction that varied in length depending upon the relative importance of direct and indirect effects. However, in contrast to CC models, we found that the less competitive species are more affected by habitat destruction. The best competitors can sometimes even be positively affected by habitat destruction, which corresponds well with the results of field studies. Our results are complementary to those results found in CC models of metacommunity dynamics. From a conservation perspective, our results illustrate that landscape alteration jeopardizes species coexistence in patchy landscapes through complex indirect effects and delayed extinctions patterns

Immigration Rates in Fragmented Landscapes – Empirical Evidence for the Importance of Habitat Amount for Species Persistence

BACKGROUND: The total amount of native vegetation is an important property of fragmented landscapes and is known to exert a strong influence on population and metapopulation dynamics. As the relationship between habitat loss and local patch and gap characteristics is strongly non-linear, theoretical models predict that immigration rates should decrease dramatically at low levels of remaining native vegetation cover, leading to patch-area effects and the existence of species extinction thresholds across fragmented landscapes with different proportions of remaining native vegetation. Although empirical patterns of species distribution and richness give support to these models, direct measurements of immigration rates across fragmented landscapes are still lacking. METHODOLOGY/PRINCIPAL FINDINGS: Using the Brazilian Atlantic forest marsupial Gray Slender Mouse Opossum (Marmosops incanus) as a model species and estimating demographic parameters of populations in patches situated in three landscapes differing in the total amount of remaining forest, we tested the hypotheses that patch-area effects on population density are apparent only at intermediate levels of forest cover, and that immigration rates into forest patches are defined primarily by landscape context surrounding patches. As expected, we observed a positive patch-area effect on M. incanus density only within the landscape with intermediate forest cover. Density was independent of patch size in the most forested landscape and the species was absent from the most deforested landscape. Specifically, the mean estimated numbers of immigrants into small patches were lower in the landscape with intermediate forest cover compared to the most forested landscape. CONCLUSIONS/SIGNIFICANCE: Our results reveal the crucial importance of the total amount of remaining native vegetation for species persistence in fragmented landscapes, and specifically as to the role of variable immigration rates in providing the underlying mechanism that drives both patch-area effects and species extinction thresholds