Increased demyelination and axonal damage in metallothionein I+II-deficient mice during experimental autoimmune encephalomyelitis

Metallothioneins I+II (MT-I+II) are antioxidant, neuroprotective factors. We previously showed that MT-I+II deficiency during experimental autoimmune encephalomyelitis (EAE) leads to increased disease incidence and clinical symptoms. Moreover, the inflammatory response of macrophages and T cells, oxidative stress, and apoptotic cell death during EAE were increased by MT-I+II deficiency. We now show for the first time that demyelination and axonal damage are significantly increased in MT-I+II deficient mice during EAE. Furthermore, oligodendroglial regeneration, growth cone formation, and tissue repair including expression of trophic factors were significantly reduced in MT-I+II-deficient mice during EAE. Accordingly, MT-I+II have protective and regenerative roles in the brain. Received 31 October 2002; received after revision 23 November 2002; accepted 26 November 2002 RID="*" ID="*"Corresponding author. M. Penkowa and C. Espejo contributed equally to this paper.     

Design and evaluation of a diabody to improve protection against a potent scorpion neurotoxin

Diabodies are recombinant, dimeric, antibody-based molecules composed of two non-covalently associated single-chain antibody fragments that bind to an antigen in a divalent manner. In an attempt to develop more effective therapeutic molecules against scorpion venoms, we designed a diabody derived from monoclonal antibody 9C2, which neutralizes the toxicity of scorpion neurotoxin AahI in mammals. The recombinant diabody produced in the periplasm of Escherichia coli was purified to homogeneity in a single step by protein L-agarose affinity chromatography. It was functional, and possessed a high binding affinity to AahI (8 x 10(-11) M). The bivalence of the diabody was confirmed by size-exclusion chromatography, isoelectrofocussing and electron microscopic observations. Finally, the diabody showed high thermal stability in serum and demonstrated protective activity when injected intraperitoneally in mice experimentally envenomed with toxin AahI. In conclusion, the diabody format gives the 9C2 molecule advantageous properties that are particularly important for potential clinical applications in the treatment of envenomations.     

Ordering and manipulation of the magnetic moments in large-scale superconducting pi-loop arrays

The phase of the macroscopic electron-pair wavefunction in a superconductor can vary only by multiples of 2pi when going around a closed contour. This results in quantization of magnetic flux, one of the most striking demonstrations of quantum phase coherence in superconductors. By using superconductors with unconventional pairing symmetry, or by incorporating pi-Josephson junctions, a phase shift of pi can be introduced in such loops. Under appropriate conditions, this phase shift results in doubly degenerate time-reversed ground states, which are characterized by the spontaneous generation of half quanta of magnetic flux, with magnitude 1/2 Phi(0)(Phi(0) = h/2e = 2.07 x 10(-15) Wb) (ref. 7). Until now, it has only been possible to generate individual half flux quanta. Here we report the realization of large-scale coupled pi-loop arrays based on YBa2Cu3O7-Au-Nb Josephson contacts. Scanning SQUID (superconducting quantum interference device) microscopy has been used to study the ordering of half flux quanta in these structures. The possibility of manipulating the polarities of individual half flux quanta is also demonstrated. These pi-loop arrays are of interest as model systems for studying magnetic phenomena--including frustration effects--in Ising antiferromagnets. Furthermore, studies of coupled pi-loops can be useful for designing quantum computers based on flux-qubits with viable quantum error correction capabilities.     

Dynamical coupling of wind and ocean waves through wave-induced air flow

Understanding the physical mechanisms behind the generation of ocean waves by wind has been a longstanding challenge. Previous studies have assumed that ocean waves induce fluctuations in velocity and pressure of the overlying air that are synchronized with the waves, and numerical models have supported this assumption. In a complex feedback, these fluctuations provide the energy for wave generation. The spatial and temporal structure of the wave-induced airflow therefore holds the key to the physics of wind-wave coupling, but detailed observations have proved difficult. Here we present an analysis of wind velocities and ocean surface elevations observed over the open ocean. We use a linear filter to identify the wave-induced air flow from the measurements and find that its structure is in agreement with 'critical-layer' theory. Considering that the wave-induced momentum flux is then controlled by the wave spectrum and that it varies considerably in vertical direction, a simple parameterization of the total air-sea momentum flux is unlikely to exist.     

Early optical emission from the gamma-ray burst of 4 October 2002

Observations of the long-lived emission--or 'afterglow'--of long-duration gamma-ray bursts place them at cosmological distances, but the origin of these energetic explosions remains a mystery. Observations of optical emission contemporaneous with the burst of gamma-rays should provide insight into the details of the explosion, as well as into the structure of the surrounding environment. One bright optical flash was detected during a burst, but other efforts have produced negative results. Here we report the discovery of the optical counterpart of GRB021004 only 193 seconds after the event. The initial decline is unexpectedly slow and requires varying energy content in the gamma-ray burst blastwave over the course of the first hour. Further analysis of the X-ray and optical afterglow suggests additional energy variations over the first few days.     

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.     

Disruption of fragmented parent bodies as the origin of asteroid families

Asteroid families are groups of small bodies that share certain orbit and spectral properties. More than 20 families have now been identified, each believed to have resulted from the collisional break-up of a large parent body in a regime where gravity controls the outcome of the collision more than the material strength of the rock. The size and velocity distributions of the family members provide important constraints for testing our understanding of the break-up process, but erosion and dynamical diffusion of the orbits over time can erase the original signature of the collision. The recently identified young Karin family provides a unique opportunity to study a collisional outcome almost unaffected by orbit evolution. Here we report numerical simulations modelling classes of collisions that reproduce the main characteristics of the Karin family. The sensitivity of the outcome of the collision to the internal structure of the parent body allows us to show that the family must have originated from the break-up of a pre-fragmented parent body, and that all large family members formed by the gravitational reaccumulation of smaller bodies. We argue that most of the identified asteroid families are likely to have had a similar history.     

Energetic neutral atoms from a trans-Europa gas torus at Jupiter

The space environments--or magnetospheres--of magnetized planets emit copious quantities of energetic neutral atoms (ENAs) at energies between tens of electron volts to hundreds of kiloelectron volts (keV). These energetic atoms result from charge exchange between magnetically trapped energetic ions and cold neutral atoms, and they carry significant amounts of energy and mass from the magnetospheres. Imaging their distribution allows us to investigate the structure of planetary magnetospheres. Here we report the analysis of 50-80 keV ENA images of Jupiter's magnetosphere, where two distinct emission regions dominate: the upper atmosphere of Jupiter itself, and a torus of emission residing just outside the orbit of Jupiter's satellite Europa. The trans-Europa component shows that, unexpectedly, Europa generates a gas cloud comparable in gas content to that associated with the volcanic moon Io. The quantity of gas found indicates that Europa has a much greater impact than hitherto believed on the structure of, and the energy flow within, Jupiter's magnetosphere.