Preselection of retrovirally transduced bone marrow avoids subsequent stem cell gene silencing and age-dependent extinction of expression of human β-globin in engrafted mice

Transcriptional silencing of genes transferred into hematopoietic stem cells poses one of the most significant challenges to the success of gene therapy. If the transferred gene is not completely silenced, a progressive decline in gene expression as the mice age often is encountered. These phenomena were observed to various degrees in mouse transplant experiments using retroviral vectors containing a human β-globin gene, even when cis-linked to locus control region derivatives. Here, we have investigated whether ex vivo preselection of retrovirally transduced stem cells on the basis of expression of the green fluorescent protein driven by the CpG island phosphoglycerate kinase promoter can ensure subsequent long-term expression of a cis-linked β-globin gene in the erythroid lineage of transplanted mice. We observed that 100% of mice (n = 7) engrafted with preselected cells concurrently expressed human β-globin and the green fluorescent protein in 20–95% of their RBC for up to 9.5 mo posttransplantation, the longest time point assessed. This expression pattern was successfully transferred to secondary transplant recipients. In the presence of β-locus control region hypersensitive site 2 alone, human β-globin mRNA expression levels ranged from 0.15% to 20% with human β-globin chains detected by HPLC. Neither the proportion of positive blood cells nor the average expression levels declined with time in transplanted recipients. Although suboptimal expression levels and heterocellular position effects persisted, in vivo stem cell gene silencing and age-dependent extinction of expression were avoided. These findings support the further investigation of this type of vector for the gene therapy of human hemoglobinopathies.

Monophyly and extensive extinction of advanced eusocial bees: Insights from an unexpected Eocene diversity

Advanced eusociality sometimes is given credit for the ecological success of termites, ants, some wasps, and some bees. Comprehensive study of bees fossilized in Baltic amber has revealed an unsuspected middle Eocene (ca. 45 million years ago) diversity of eusocial bee lineages. Advanced eusociality arose once in the bees with significant post-Eocene losses in diversity, leaving today only two advanced eusocial tribes comprising less than 2% of the total bee diversity, a trend analogous to that of hominid evolution. This pattern of changing diversity contradicts notions concerning the role of eusociality for evolutionary success in insects.

Metapopulation extinction caused by mutation accumulation

Theory suggests that the risk of extinction by mutation accumulation can be comparable to that by environmental stochasticity for an isolated population smaller than a few thousand individuals. Here we show that metapopulation structure, habitat loss or fragmentation, and environmental stochasticity can be expected to greatly accelerate the accumulation of mildly deleterious mutations, lowering the genetic effective size to such a degree that even large metapopulations may be at risk of extinction. Because of mutation accumulation, viable metapopulations may need to be far larger and better connected than would be required under just stochastic demography.

The current biodiversity extinction event: Scenarios for mitigation and recovery

The current massive degradation of habitat and extinction of species is taking place on a catastrophically short timescale, and their effects will fundamentally reset the future evolution of the planet's biota. The fossil record suggests that recovery of global ecosystems has required millions or even tens of millions of years. Thus, intervention by humans, the very agents of the current environmental crisis, is required for any possibility of short-term recovery or maintenance of the biota. Many current recovery efforts have deficiencies, including insufficient information on the diversity and distribution of species, ecological processes, and magnitude and interaction of threats to biodiversity (pollution, overharvesting, climate change, disruption of biogeochemical cycles, introduced or invasive species, habitat loss and fragmentation through land use, disruption of community structure in habitats, and others). A much greater and more urgently applied investment to address these deficiencies is obviously warranted. Conservation and restoration in human-dominated ecosystems must strengthen connections between human activities, such as agricultural or harvesting practices, and relevant research generated in the biological, earth, and atmospheric sciences. Certain threats to biodiversity require intensive international cooperation and input from the scientific community to mitigate their harmful effects, including climate change and alteration of global biogeochemical cycles. In a world already transformed by human activity, the connection between humans and the ecosystems they depend on must frame any strategy for the recovery of the biota.

Unusual dynamics of extinction in a simple ecological model.

Studies on natural populations and harvesting biological resources have led to the view, commonly held, that (i) populations exhibiting chaotic oscillations run a high risk of extinction; and (ii) a decrease in emigration/exploitation may reduce the risk of extinction. Here we describe a simple ecological model with emigration/depletion that shows behavior in contrast to this. This model displays unusual dynamics of extinction and survival, where populations growing beyond a critical rate can persist within a band of high depletion rates, whereas extinction occurs for lower depletion rates. Though prior to extinction at lower depletion rates the population exhibits chaotic dynamics with large amplitudes of variation and very low minima, at higher depletion rates the population persists at chaos but with reduced variation and increased minima. For still higher values, within the band of persistence, the dynamics show period reversal leading to stability. These results illustrate that chaos does not necessarily lead to population extinction. In addition, the persistence of populations at high depletion rates has important implications in the considerations of strategies for the management of biological resources.

Avoiding Extinction: An Evaluation of Short-Term Recovery Recommendations for the Endangered Rio Grande Silvery Minnow

The endangered Rio Grande silvery minnow (Hybognathus amarus; RGSM) is nearing extinction and requires immediate recovery actions. In a draft report to the Middle Rio Grande Program, a Program Advisory Panel (PAP) recommended 34 short-term recovery measures to be implemented within the next five years, and 21 long-term recovery actions. However, these recommendations need further analysis to determine if and how the actions could be implemented. This project evaluated short-term recommendations provided by the PAP to identify the most effective and rank the relative importance of the actions. These recommendations were divided into 7 recovery categories: population augmentation (5 recommendations); hydrologic regimen (4 recommendations); physical habitat (3 recommendations); biological component of habitat (2 recommendations); population monitoring (6 recommendations); monitoring, analysis, and modeling (12 recommendations); and information and planning (2 recommendations). Each recommendation was evaluated for its potential to produce anticipated recovery progress for the RGSM based on assessments of the degree of feasibility, cost effectiveness, and associated potential consequences if fully implemented. In addition, other alternatives in a range of options were also considered where applicable. In each case, recommendations were evaluated from on-site visits, interviews with researchers and resource managers, and literature review. Based on the research findings, three major groupings of the recovery categories were identified: natural aspects of recovery, program aspects of recovery, and emergency measures. At least one recovery category within each major grouping was considered important by the respondents, which indicates that each grouping is of high importance in relation to the situation at hand. However, actions within each grouping have varying priorities given constraints on available resources, time, and budget. An integrated approach that accounts for the complexity of the river system and the species itself was considered the best approach to avoid extinction while ensuring long-term sustainability. Results of these analyses were provided directly to the PAP for their review, and it is anticipated that project results could advance implementation of the most appropriate immediate recovery actions needed to prevent extinction of the RGSM.

Extinction trends of threatened invertebrates in peninsular Spain

Using information from two recently published atlases of threatened invertebrate species in peninsular Spain, we examined the climatic, land use and geographic characteristics of the 100 km2 UTM cells with most likelihood of suffering extinctions (extinction cells), as well as the attributes of the species prone to population extinctions. Extinction cells have had significantly (1) lower precipitation values, (2) higher temperatures, (3) higher percentages of anthropic land uses or (4) higher rates of anthropization during the last 20 years than the remaining cells. Nevertheless, probable extinctions may occur under a wide range of climatic and anthropization change rates and these variables can only explain a low proportion (~5 %) of variability in the occurrence or number of extinction cells. Aquatic species seem to suffer higher local extinction rates than terrestrial species. Interestingly, many invertebrate species with approximately 25 or less occurrence cells are on a clear trajectory towards extinction. These results outline the difficulties and uncertainties in relating probable population extinctions with climatic and land use changes in the case of invertebrate data. However, they also suggest that a third of the considered Spanish threatened species could have lost some of their populations, and that current conservation efforts are insufficient to reverse this tendency.

Evolution of the last koninckinids (Athyridida, Koninckinidae), a precursor signal of the early Toarcian mass extinction event in the Western Tethys

Koninckinids are a suitable group to shed light on the biotic crisis suffered by brachiopod fauna in the Early Jurassic. Koninckinid fauna recorded in the late Pliensbachian–early Toarcian from the easternmost Subbetic basin is analyzed and identified as a precursor signal for one of the most conspicuous mass extinction events of the Phylum Brachiopoda, a multi-phased interval with episodes of changing environmental conditions, whose onset can be detected from the Elisa–Mirabile subzones up to the early Toarcian extinction boundary in the lowermost Serpentinum Zone (T-OAE). The koninckinid fauna had a previously well-established migration pattern from the intra-Tethyan to the NW-European basins but a first phase with a progressive warming episode in the Pliensbachian–Toarcian transition triggered a koninckinid fauna exodus from the eastern/central Tethys toward the westernmost Mediterranean margins. A second stage shows an adaptive response to more adverse conditions in the westernmost Tethyan margins and finally, an escape and extinction phase is detected in the Atlantic areas from the mid-Polymorphum Zone onwards up to their global extinction in the lowermost Serpentinum Zone. This migration pattern is independent of the paleogeographic bioprovinciality and is unrelated to a facies-controlled pattern. The anoxic/suboxic environmental conditions should only be considered as a minor factor of partial control since well-oxygenated habitats are noted in the intra-Tethyan basins and this factor is noticeable only in the second westward migratory stage (with dwarf taxa and oligotypical assemblages). The analysis of cold-seep proxies in the Subbetic deposits suggests a radiation that is independent of methane releases in the Subbetic basin.

Opinions in cases of debt, 1748-1749

Opinions rendered in cases brought against Thomas Barker, executor of the estate of Robert Forstor, by James and Roger Barlow (executors of the estate of Thomas Forster), Sibylla Price, and Richard Foster. The attorney for all plaintiffs was Samuel Swann.

[ Warrant for the arrest of Samuel Gray for debt], 1769

A warrant for the arrest and sale of all assets of Gray who was found to owe another merchant Alexander Hill in a recent trial. Also includes appraisal of property by Fairfield and Salter and statement by Sheriff Cudworth.

[Receipt for certificates of funded debt], 1791 January 28

Printed Commissioner's Office receipt form acknowledging three certificates of funded debt received by Caleb Gannett from Nathaniel Appleton, Commissioner of Loans in the State of Massachusetts. The receipt, No. 712, is signed by Gannett and dated January 28, 1791.

Banking Union with a Sovereign Virus. The self-serving regulatory treatment of sovereign debt in the euro area. CEPS Policy Brief No. 289, 27 March 2013

In many eurozone countries, domestic banks often hold more than 20% of domestic public debt, which is an unsatisfactory situation given that banks are highly leveraged and that sovereign debt is inherently subject to default risk within the euro area. This paper by Daniel Gros finds, however, that the relative concentration of public debt on bank balance sheets is not just a result of the euro crisis, for there are strong additional incentives for banks in some countries to increase their sovereign. His contribution discusses a number of these regulatory incentives – the most important of which is specific to the euro area – and explores ways in which euro area banks can be weaned from massive investments in government bonds.