Inhibition of precipitin formation in the guinea-pig with cyclophosphamide

Zusammenfassung Cyclophosphamid (aber nicht 6-Mercaptopurin oder Vincaleukoblastin) verhindert die primäre Antikörperbildung beim Meerschweinchen. Auch bei fortgesetzter Stimulation mit dem spezifischen Antigen bleiben die Tiere relativ refraktär. Dieser Hemmeffekt wird weitgehend aufgehoben, wenn das Antigen mit Freund's Adjuvans injiziert wird.

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Aided by a grant from the American Cancer Society.     

Distribution and abundance of birds in the White Mountains, California

This paper quantifies the distribution and abundance of birds in the White Mountains, Inyo and Mono counties, California, during spring-summer 1989-91, to establish a baseline for monitoring the area's avifauna. Overall 58 species were encountered in the single-leaf pinyon-Utah juniper ( Pinus monophylla-Juniperus osteosperma ) zone, and 61 species in the bristlecone-limber pine ( P. longaeva-P. flexilis ) zone. The bristlecone-limber pine zone had a significantly greater overall bird abundance relative to the pinyon-juniper. Both zones were characterized by few very abundant species, a few moderately abundant species, and numerous rare species. The Black-throated Gray Warbler (scientific names in tables), Gray Flycatcher, and Pinyon Jay were the most abundant species in the pinyon-juniper whereas the Clark's Nutcracker, Mountain Chickadee, and Cassin's Finch were the most abundant species in the bristlecone-limber pine. There were few ecological or taxonomic replacements of species between zones, with the differences in distribution and abundance related primarily to the interaction between elevation and vegetation. Significant inter-year variation in abundance was found for about 20 species in each zone—more species showed declining rather than increasing trends. The Mountain Chickadee and White-breasted Nuthatch declined, whereas the Gray Flycatcher and Rock Wren increased across years in both zones. Reasons for declines in some species might be the severe drought that continued throughout this study.     

Phylogenetic divergence in a desert fish: differentiation of speckled dace within the Bonneville, Lahontan, and upper Snake river basins

Historical events have had a great impact on the biogeography of fishes of western North America. We examined the genetic variation of the speckled dace ( Rhinichthys osculus ) to determine the effects on this species of extensive hydrological changes during the last 10 million years in the Bonneville and Lahontan basins of the Great Basin and the upper Snake River Basin. Eight hundred sixty-nine base pairs of the mitochondrial gene cytochrome b were sequenced from 97 individuals representing 22 populations within these 3 basins, as well as from 2 individuals of longnose dace ( Rhinichthys cataractae ) that served as outgroups. Additionally, 13 speckled dace sequences representing 3 Bonneville populations were used from GenBank. Phylogenetic relationships were reconstructed using maximum parsimony and maximum likelihood criteria. Analysis of molecular variance was used to determine population structure and to estimate the amount of gene flow across the community boundaries. Three distinct clades were reconstructed representing the Lahontan Basin, the northern Bonneville and upper Snake River basins, and the southern Bonneville Basin. Additionally, most of the population structuring was explained by variation among basins (65.33%). Speckled dace demonstrated high genetic variation. As hypothesized, the northern and southern Bonneville specimens formed separate clades; however, the southern Bonneville clade was basal to a sister clade formed by the northern Bonneville/upper Snake River and Lahontan clades. These relationships indicate that Pliocene connections between the Snake, Lahontan, and Bonneville drainages, rather than more recent Pleistocene connections, best explain population structuring in speckled dace.     

Has the Earth's sixth mass extinction already arrived?

Palaeontologists characterize mass extinctions as times when the Earth loses more than three-quarters of its species in a geologically short interval, as has happened only five times in the past 540?million years or so. Biologists now suggest that a sixth mass extinction may be under way, given the known species losses over the past few centuries and millennia. Here we review how differences between fossil and modern data and the addition of recently available palaeontological information influence our understanding of the current extinction crisis. Our results confirm that current extinction rates are higher than would be expected from the fossil record, highlighting the need for effective conservation measures.     

Exclusion of a luminous red giant as a companion star to the progenitor of supernova SN 2011fe

Type Ia supernovae are thought to result from a thermonuclear explosion of an accreting white dwarf in a binary system, but little is known of the precise nature of the companion star and the physical properties of the progenitor system. There are two classes of models: double-degenerate (involving two white dwarfs in a close binary system) and single-degenerate models. In the latter, the primary white dwarf accretes material from a secondary companion until conditions are such that carbon ignites, at a mass of 1.38 times the mass of the Sun. The type Ia supernova SN 2011fe was recently detected in a nearby galaxy. Here we report an analysis of archival images of the location of SN 2011fe. The luminosity of the progenitor system (especially the companion star) is 10-100 times fainter than previous limits on other type Ia supernova progenitor systems, allowing us to rule out luminous red giants and almost all helium stars as the mass-donating companion to the exploding white dwarf.     

Patterns and rates of exonic de novo mutations in autism spectrum disorders

Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified. To identify further genetic risk factors, here we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n = 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant, and the overall rate of mutation is only modestly higher than the expected rate. In contrast, the proteins encoded by genes that harboured de novo missense or nonsense mutations showed a higher degree of connectivity among themselves and to previous ASD genes as indexed by protein-protein interaction screens. The small increase in the rate of de novo events, when taken together with the protein interaction results, are consistent with an important but limited role for de novo point mutations in ASD, similar to that documented for de novo copy number variants. Genetic models incorporating these data indicate that most of the observed de novo events are unconnected to ASD; those that do confer risk are distributed across many genes and are incompletely penetrant (that is, not necessarily sufficient for disease). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5- to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favour of CHD8 and KATNAL2 as genuine autism risk factors.     

Crystal structure of the CorA Mg2+ transporter

The magnesium ion, Mg2+, is essential for myriad biochemical processes and remains the only major biological ion whose transport mechanisms remain unknown. The CorA family of magnesium transporters is the primary Mg2+ uptake system of most prokaryotes and a functional homologue of the eukaryotic mitochondrial magnesium transporter. Here we determine crystal structures of the full-length Thermotoga maritima CorA in an apparent closed state and its isolated cytoplasmic domain at 3.9 A and 1.85 A resolution, respectively. The transporter is a funnel-shaped homopentamer with two transmembrane helices per monomer. The channel is formed by an inner group of five helices and putatively gated by bulky hydrophobic residues. The large cytoplasmic domain forms a funnel whose wide mouth points into the cell and whose walls are formed by five long helices that are extensions of the transmembrane helices. The cytoplasmic neck of the pore is surrounded, on the outside of the funnel, by a ring of highly conserved positively charged residues. Two negatively charged helices in the cytoplasmic domain extend back towards the membrane on the outside of the funnel and abut the ring of positive charge. An apparent Mg2+ ion was bound between monomers at a conserved site in the cytoplasmic domain, suggesting a mechanism to link gating of the pore to the intracellular concentration of Mg2+.     

BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes

During lymphocyte development, the assembly of genes coding for antigen receptors occurs by the combinatorial linking of gene segments. The stochastic nature of this process gives rise to lymphocytes that can recognize self-antigens, thereby having the potential to induce autoimmune disease. Such autoreactive lymphocytes can be silenced by developmental arrest or unresponsiveness (anergy), or can be deleted from the repertoire by cell death. In the thymus, developing T lymphocytes (thymocytes) bearing a T-cell receptor (TCR)-CD3 complex that engages self-antigens are induced to undergo programmed cell death (apoptosis), but the mechanisms ensuring this 'negative selection' are unclear. We now report that thymocytes lacking the pro-apoptotic Bcl-2 family member Bim (also known as Bcl2l11) are refractory to apoptosis induced by TCR-CD3 stimulation. Moreover, in transgenic mice expressing autoreactive TCRs that provoke widespread deletion, Bim deficiency severely impaired thymocyte killing. TCR ligation upregulated Bim expression and promoted interaction of Bim with Bcl-XL, inhibiting its survival function. These findings identify Bim as an essential initiator of apoptosis in thymocyte-negative selection.