A gene in the multidrug and toxic compound extrusion (MATE) family confers aluminum tolerance in sorghum

Crop yields are significantly reduced by aluminum toxicity on highly acidic soils, which comprise up to 50% of the world's arable land. Candidate aluminum tolerance proteins include organic acid efflux transporters, with the organic acids forming non-toxic complexes with rhizosphere aluminum. In this study, we used positional cloning to identify the gene encoding a member of the multidrug and toxic compound extrusion (MATE) family, an aluminum-activated citrate transporter, as responsible for the major sorghum (Sorghum bicolor) aluminum tolerance locus, Alt(SB). Polymorphisms in regulatory regions of Alt(SB) are likely to contribute to large allelic effects, acting to increase Alt(SB) expression in the root apex of tolerant genotypes. Furthermore, aluminum-inducible Alt(SB) expression is associated with induction of aluminum tolerance via enhanced root citrate exudation. These findings will allow us to identify superior Alt(SB) haplotypes that can be incorporated via molecular breeding and biotechnology into acid soil breeding programs, thus helping to increase crop yields in developing countries where acidic soils predominate.     

A Revolution that never happened

If we define scientific revolutions as changes of scientists' ontologies, types of causal explanation, and paradigmatic types of methods and instruments, Antoine-Laurent Lavoisier's contribution to chemistry did not amount to a scientific revolution. Contrary to the received view that Lavoisier initiated a “chemical revolution,” which is accepted by Chang and Kusch, I argue that Lavoisier shared with the phlogistonists their “flat ontology” of chemical substance, established decades before the 1770s, their types of explaining chemical transformation, and their quantitative methods. Based on my historical reconstruction, I criticize Chang's argument that the late eighteenth-century phlogistic systems and Lavoisier's system belonged to two different theoretical traditions. As a consequence, I also question Chang's argument that the acceptance of Lavoisier's system can be explained in terms of dominance of “compositionism” over “principlism.”     

A Machine Learning Approach for Mechanism Selection in Complex Negotiations

Automated negotiation mechanisms can be helpful in contexts where users want to reach mutually satisfactory agreements about issues of shared interest, especially for complex problems with many interdependent issues. A variety of automated negotiation mechanisms have been proposed in the literature. The effectiveness of those mechanisms, however, may depend on the characteristics of the underlying negotiation problem (e.g. on the complexity of participant’s utility functions, as well as the degree of conflict between participants). While one mechanism may be a good choice for a negotiation problem, it may be a poor choice for another. In this paper, we pursue the problem of selecting the most effective negotiation mechanism given a particular problem by (1) defining a set of scenario metrics to capture the relevant features of negotiation problems, (2) evaluating the performance of a range of negotiation mechanisms on a diverse test suite of negotiation scenarios, (3) applying machine learning techniques to identify which mechanisms work best with which scenarios, and (4) demonstrating that using these classification rules for mechanism selection enables significantly better negotiation performance than any single mechanism alone.     

The Prussian Mining Official Alexander von Humboldt

From summer 1792 until spring 1797, Alexander von Humboldt was a mining official in the Franconian parts of Prussia. He visited mines, inspected smelting works, calculated budgets, wrote official reports, founded a mining school, performed technological experiments, and invented a miners’ lamp and respirator. At the same time he also participated in the Republic of Letters, corresponded with savants in all Europe, and was a member of the Leopoldine Carolinian Academy and the Berlin Gesellschaft Naturforschender Freunde. He collected minerals, made geognostic observations, performed chemical and physiological experiments, read the newest scientific journals, and prepared and published texts on mineralogy, geognosy, chemistry, botany and physiology. Humboldt did his scientific investigations alongside his administrative and technical work. This raises the question of whether there were fruitful interactions between Humboldt's technical-administrative work and (parts of) his natural inquiry. I argue that the mining official Humboldt was a late eighteenth-century figure of hybrid savant-technician. Mines and smelting works provided numerous opportunities for studies of nature. Humboldt systematically used inspection tours for mineralogical and geognostic observations. He transformed mines into chemical laboratories, and he transferred knowledge and material items from his natural inquiries in mines to academic institutions. The main objective of this paper is to illuminate the persona of savant-technician (or scientific-technological expert) along with Humboldt's mixed technological and scientific work during his term as mining official.     

Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness

Using exome sequencing, we identify SERAC1 mutations as the cause of MEGDEL syndrome, a recessive disorder of dystonia and deafness with Leigh-like syndrome, impaired oxidative phosphorylation and 3-methylglutaconic aciduria. We localized SERAC1 at the interface between the mitochondria and the endoplasmic reticulum in the mitochondria-associated membrane fraction that is essential for phospholipid exchange. A phospholipid analysis in patient fibroblasts showed elevated concentrations of phosphatidylglycerol-34:1 (where the species nomenclature denotes the number of carbon atoms in the two acyl chains:number of double bonds in the two acyl groups) and decreased concentrations of phosphatidylglycerol-36:1 species, resulting in an altered cardiolipin subspecies composition. We also detected low concentrations of bis(monoacyl-glycerol)-phosphate, leading to the accumulation of free cholesterol, as shown by abnormal filipin staining. Complementation of patient fibroblasts with wild-type human SERAC1 by lentiviral infection led to a decrease and partial normalization of the mean ratio of phosphatidylglycerol-34:1 to phosphatidylglycerol-36:1. Our data identify SERAC1 as a key player in the phosphatidylglycerol remodeling that is essential for both mitochondrial function and intracellular cholesterol trafficking.     

HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease)

Autosomal recessive severe congenital neutropenia (SCN) constitutes a primary immunodeficiency syndrome associated with increased apoptosis in myeloid cells, yet the underlying genetic defect remains unknown. Using a positional cloning approach and candidate gene evaluation, we identified a recurrent homozygous germline mutation in HAX1 in three pedigrees. After further molecular screening of individuals with SCN, we identified 19 additional affected individuals with homozygous HAX1 mutations, including three belonging to the original pedigree described by Kostmann. HAX1 encodes the mitochondrial protein HAX1, which has been assigned functions in signal transduction and cytoskeletal control. Here, we show that HAX1 is critical for maintaining the inner mitochondrial membrane potential and protecting against apoptosis in myeloid cells. Our findings suggest that HAX1 is a major regulator of myeloid homeostasis and underline the significance of genetic control of apoptosis in neutrophil development.     

A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable

The small intestine epithelium renews every 2 to 5 days, making it one of the most regenerative mammalian tissues. Genetic inducible fate mapping studies have identified two principal epithelial stem cell pools in this tissue. One pool consists of columnar Lgr5-expressing cells that cycle rapidly and are present predominantly at the crypt base. The other pool consists of Bmi1-expressing cells that largely reside above the crypt base. However, the relative functions of these two pools and their interrelationship are not understood. Here we specifically ablated Lgr5-expressing cells in mice using a human diphtheria toxin receptor (DTR) gene knocked into the Lgr5 locus. We found that complete loss of the Lgr5-expressing cells did not perturb homeostasis of the epithelium, indicating that other cell types can compensate for the elimination of this population. After ablation of Lgr5-expressing cells, progeny production by Bmi1-expressing cells increased, indicating that Bmi1-expressing stem cells compensate for the loss of Lgr5-expressing cells. Indeed, lineage tracing showed that Bmi1-expressing cells gave rise to Lgr5-expressing cells, pointing to a hierarchy of stem cells in the intestinal epithelium. Our results demonstrate that Lgr5-expressing cells are dispensable for normal intestinal homeostasis, and that in the absence of these cells, Bmi1-expressing cells can serve as an alternative stem cell pool. These data provide the first experimental evidence for the interrelationship between these populations. The Bmi1-expressing stem cells may represent both a reserve stem cell pool in case of injury to the small intestine epithelium and a source for replenishment of the Lgr5-expressing cells under non-pathological conditions.     

Shifting ontologies, changing classifications: plant materials from 1700 to 1830

This paper studies European chemists’ shifting ontologies of materials by comparing the ways in which they classified materials. The focus is on plant materials, their different identities, and the changing ways chemists sorted out and ordered plant materials in the eighteenth and early nineteenth centuries. The main goals of the paper are to follow the development of plant materials from ordinary, everyday materials and commodities in the early eighteenth century to purified carbon compounds and organic substances familiar only to experts in the 1830s, and to reconstruct chemists’ ways of classifying these objects in different practical and intellectual contexts.The study of changes in European chemists’ ways of classifying plant materials over more than a century brings to the foreground a trajectory of ontological shifts that is ‘punctuated’ in the 1750s, the 1790s, and the 1830s. Early eighteenth-century plant materials, which were commodities of the apothecary trade and other arts and crafts, were elevated epistemically as compound components or ‘proximate principles’ of plants in the 1750s, reduced to organic compounds in the 1790s, and replaced by carbon compounds in the 1830s. The last, third transformation of the epistemic constitution of materials and the mode of their classification was accompanied by a deep transformation of the material culture of plant chemistry. After the late 1830s, many of the eighteenth-century vegetable commodities disappeared from chemists’ agenda or were split into different substances individuated and identified in new ways. Coal tar products, and new organic artefacts containing chlorine or bromine, entered the chemical laboratory in the 1820s and became fused with the purified rest of the previous plant and animal substances. The material objects of the new culture of organic chemistry became detached from the materials applied in the extant arts and crafts. It was only in the late 1850s, with the rise of the synthetic dye industry, that a great number of these laboratory substances became involved in industrial production.