The cost of inbreeding in Arabidopsis

Population geneticists have long sought to estimate the distribution of selection intensities among genes of diverse function across the genome. Only recently have DNA sequencing and analytical techniques converged to make this possible. Important advances have come from comparing genetic variation within species (polymorphism) with fixed differences between species (divergence). These approaches have been used to examine individual genes for evidence of selection. Here we use the fact that the time since species divergence allows combination of data across genes. In a comparison of amino-acid replacements among species of the mustard weed Arabidopsis with those among species of the fruitfly Drosophila, we find evidence for predominantly beneficial gene substitutions in Drosophila but predominantly detrimental substitutions in Arabidopsis. We attribute this difference to the Arabidopsis mating system of partial self-fertilization, which corroborates a prediction of population genetics theory that species with a high frequency of inbreeding are less efficient in eliminating deleterious mutations owing to their reduced effective population size.     

Species-specific responses of Late Quaternary megafauna to climate and humans

Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.     

Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction

Dysfunction of the exocrine pancreas is observed in diabetes, but links between concurrent exocrine and endocrine pancreatic disease and contributing genetic factors are poorly characterized. We studied two families with diabetes and exocrine pancreatic dysfunction by genetic, physiological and in vitro functional studies. A genome-wide screen in Family 1 linked diabetes to chromosome 9q34 (maximal lod score 5.07). Using fecal elastase deficiency as a marker of exocrine pancreatic dysfunction refined the critical chromosomal region to 1.16 Mb (maximal lod score 11.6). Here, we identified a single-base deletion in the variable number of tandem repeats (VNTR)-containing exon 11 of the carboxyl ester lipase (CEL) gene, a major component of pancreatic juice and responsible for the duodenal hydrolysis of cholesterol esters. Screening subjects with maturity-onset diabetes of the young identified Family 2, with another single-base deletion in CEL and a similar phenotype with beta-cell failure and pancreatic exocrine disease. The in vitro catalytic activities of wild-type and mutant CEL protein were comparable. The mutant enzyme was, however, less stable and secreted at a lower rate. Furthermore, we found some evidence for an association between common insertions in the CEL VNTR and exocrine dysfunction in a group of 182 unrelated subjects with diabetes (odds ratio 4.2 (1.6, 11.5)). Our findings link diabetes to the disrupted function of a lipase in the pancreatic acinar cells.     

Discovery of the progenitor of the type Ia supernova 2007on

Type Ia supernovae are exploding stars that are used to measure the accelerated expansion of the Universe and are responsible for most of the iron ever produced. Although there is general agreement that the exploding star is a white dwarf in a binary system, the exact configuration and trigger of the explosion is unclear, which could hamper their use for precision cosmology. Two families of progenitor models have been proposed. In the first, a white dwarf accretes material from a companion until it exceeds the Chandrasekhar mass, collapses and explodes. Alternatively, two white dwarfs merge, again causing catastrophic collapse and an explosion. It has hitherto been impossible to determine if either model is correct. Here we report the discovery of an object in pre-supernova archival X-ray images at the position of the recent type Ia supernova (2007on) in the elliptical galaxy NGC 1404. Deep optical images (also archival) show no sign of this object. From this we conclude that the X-ray source is the progenitor of the supernova, which favours the accretion model for this supernova, although the host galaxy is older (6-9 Gyr) than the age at which the explosions are predicted in the accreting models.     

Energy doubling of 42 GeV electrons in a metre-scale plasma wakefield accelerator

The energy frontier of particle physics is several trillion electron volts, but colliders capable of reaching this regime (such as the Large Hadron Collider and the International Linear Collider) are costly and time-consuming to build; it is therefore important to explore new methods of accelerating particles to high energies. Plasma-based accelerators are particularly attractive because they are capable of producing accelerating fields that are orders of magnitude larger than those used in conventional colliders. In these accelerators, a drive beam (either laser or particle) produces a plasma wave (wakefield) that accelerates charged particles. The ultimate utility of plasma accelerators will depend on sustaining ultrahigh accelerating fields over a substantial length to achieve a significant energy gain. Here we show that an energy gain of more than 42 GeV is achieved in a plasma wakefield accelerator of 85 cm length, driven by a 42 GeV electron beam at the Stanford Linear Accelerator Center (SLAC). The results are in excellent agreement with the predictions of three-dimensional particle-in-cell simulations. Most of the beam electrons lose energy to the plasma wave, but some electrons in the back of the same beam pulse are accelerated with a field of approximately 52 GV m(-1). This effectively doubles their energy, producing the energy gain of the 3-km-long SLAC accelerator in less than a metre for a small fraction of the electrons in the injected bunch. This is an important step towards demonstrating the viability of plasma accelerators for high-energy physics applications.     

Dialogue and Revolution: Proposal for Critical-Pragmatic Recursive Praxis to Support Operationalisation of Methodological Virtues

Systemic Practice and Action Research (SPAR) denotes a family of approaches with different theoretical foundations, the constructive encounter between which may propel the movement forward. A persistent scholarly debate persists between the so-called emancipatory and pragmatic strands, motivating perceptions of the impossibility to jointly accomplish both ‘dialogical’ and ‘revolutionary’ commitments of the movement. This reflects that SPAR is still grappling with how to maintain a normative foundation while prioritising local change processes, thus reconciling what is universally ‘right’ with the locally ‘good’ in order to foster an operational view of the nature of reciprocity and justification. In this paper, I mobilise experiences from five action research projects in the field of natural resource governance to undertake a methodological introspection to examine how we as SPAR professionals may negotiate our approach during project implementation and the encounter of concrete realities and stakeholder interests. The objective is to offer an alternative view on the relationship between the ‘dialogical’ and the ‘revolutionary’ elements of SPAR; a view which rejects a dichotomisation in favour of a critical-pragmatic recursive praxis that depends on the capacity of the researcher to negotiate methodological virtues with co-researchers in the process.     

Evolutionary genomics: detecting selection needs comparative data

Positive selection at the molecular level is usually indicated by an increase in the ratio of non-synonymous to synonymous substitutions (dN/dS) in comparative data. However, Plotkin et al. describe a new method for detecting positive selection based on a single nucleotide sequence. We show here that this method is particularly sensitive to assumptions regarding the underlying mutational processes and does not provide a reliable way to identify positive selection.