Immunological properties of oxygen-transport proteins: hemoglobin,hemocyanin and hemerythrin

It is now well documented that peptides with enhanced or alternative functionality (termed cryptides) can be liberated from larger, and sometimes inactive, proteins. A primary example of this phenomenon is the oxygen-transport protein hemoglobin. Aside from respiration, hemoglobin and hemoglobin-derived peptides have been associated with immune modulation, hematopoiesis, signal transduction and microbicidal activities in metazoans. Likewise, the functional equivalents to hemoglobin in invertebrates, namely hemocyanin and hemerythrin, act as potent immune effectors under certain physiological conditions. The purpose of this review is to evaluate the true extent of oxygen-transport protein dynamics in innate immunity, and to impress upon the reader the multi-functionality of these ancient proteins on the basis of their structures. In this context, erythrocyte–pathogen antibiosis and the immune competences of various erythroid cells are compared across diverse taxa.     

A high-resolution map of human chromosome 12

Our sequence-tagged site-content map of chromosome 12 is now integrated with the whole-genome fingerprinting effort. It provides accurate and nearly complete bacterial clone coverage of chromosome 12. We propose that this integrated mapping protocol serves as a model for constructing physical maps for entire genomes.     

Antibody neutralization and escape by HIV-1

Neutralizing antibodies (Nab) are a principal component of an effective human immune response to many pathogens, yet their role in HIV-1 infection is unclear. To gain a better understanding of this role, we examined plasma from patients with acute HIV infection. Here we report the detection of autologous Nab as early as 52 days after detection of HIV-specific antibodies. The viral inhibitory activity of Nab resulted in complete replacement of neutralization-sensitive virus by successive populations of resistant virus. Escape virus contained mutations in the env gene that were unexpectedly sparse, did not map generally to known neutralization epitopes, and involved primarily changes in N-linked glycosylation. This pattern of escape, and the exceptional density of HIV-1 envelope glycosylation generally, led us to postulate an evolving 'glycan shield' mechanism of neutralization escape whereby selected changes in glycan packing prevent Nab binding but not receptor binding. Direct support for this model was obtained by mutational substitution showing that Nab-selected alterations in glycosylation conferred escape from both autologous antibody and epitope-specific monoclonal antibodies. The evolving glycan shield thus represents a new mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire.     

Communicating junctions between pillar cells in the gills of the atlantic hagfish,Myxine glutinosa

Summary In the respiratory lamellae of the gills of the atlantic hagfish,Myxine glutinosa, pillar cells are coupled by communicating junctions. It is suggested that these cells behave like a functional syncytium.Supported by the DFG, SFB 146. The authors are indebted to Drs F. Walvig and H. Stolte for kindly providing the hagfish. The expert technical assistance of G. Voss-Wermbter, Dipl.-Ing., and H. Heidrich is gratefully acknowledged.     

The influence of lethal X-irradiation on trace metal uptake by the mitochondrion

Zusammenfassung Die Aufnahme von Spurenmetallen durch Mitochondrien der Milz von Ratten, die letalen Dosen von Röntgenstrahlen ausgesetzt worden waren, wurde in vitro durch radioaktive Tracerisotope bestimmt. Kurz nach der Bestrahlung wurde bei Kobalt, Eisen, Nickel, Selen und Zink eine erhöhte, bei Chrom und Mangan eine verringerte Aufnahme beobachtet.     

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.