Increased productivity in the subantarctic ocean during Heinrich events

Massive iceberg discharges from the Northern Hemisphere ice sheets, 'Heinrich events', coincided with the coldest periods of the last ice age. There is widespread evidence for Heinrich events and their profound impact on the climate and circulation of the North Atlantic Ocean, but their influence beyond that region remains uncertain. Here we use a combination of molecular fingerprints of algal productivity and radioisotope tracers of sedimentation to document eight periods of increased productivity in the subpolar Southern Ocean during the past 70,000 years that occurred within 1,000-2,000 years of a Northern Hemisphere Heinrich event. We discuss possible causes for such a link, including increased supply of iron from upwelling and increased stratification during the growing season, which imply an alteration of the global ocean circulation during Heinrich events. The mechanisms linking North Atlantic iceberg discharges with subantarctic productivity remain unclear at this point. We suggest that understanding how the Southern Ocean was altered during these extreme climate perturbations is critical to understanding the role of the ocean in climate change.     

A single micromanipulated stem cell gives rise to multiple T-cell receptor gene rearrangements in the thymus in vitro

The extensive range of specificities of T-cell receptors is generated, as for immunoglobulins, by rearrangement of genetic information. Much valuable information about rearrangement processes has been inferred by comparing DNA from (monoclonal) lymphoid lines with germ-line DNA and, for B cells, from rearrangements in some Abelson murine leukaemia virus-transformed cell lines. However, because it is difficult to isolate and grow precursor populations, it has not proved possible to study rearrangements occurring in normal untransformed cells in vitro. Here we show that a single T-cell precursor colonizing an alymphoid thymus lobe in organ culture can generate multiple receptor beta-chain gene rearrangements. These observations provide unequivocal evidence for the intra-thymic diversification of the T-cell repertoire. They also offer the possibility of investigating rearrangement and its control in the clonal progeny of a single normal T-cell precursor without the perturbations involved in the use of viral transformation or the production of T-cell hybridomas.     

Acceptors for botulinum neurotoxin reside on motor nerve terminals and mediate its internalization

Botulinum neurotoxin (BoNY) type A, a causative agent of botulism, is a di-chain protein (molecular weight 140,000) from Clostridium botulinum, and the most neurotoxic substance known. Some cases of sudden infant cot deaths have been attributed to such a neuroparalytic condition. BoNT inhibits irreversibly the release of acetylcholine from peripheral nerves in a highly selective manner. Hence, it is potentially an invaluable probe for studying the mechanism of transmitter release. Here we demonstrate specific labelling of murine motor nerve terminals with neurotoxic, 125I-labelled BoNT (type A) by autoradiography. We observed saturable, temperature-sensitive binding of BoNT to sites which reside solely on the nerve terminal membrane; these were distributed on all unmyelinated areas, at an average density of 150-500 per micron2 of membrane. The binding was mediated by the larger subunit of the toxin and was inhibited partially by tetanus toxin, another microbial protein. No specific binding was detectable on any other cell types examined, including noradrenergic terminals. Following binding, internalization of radioactivity was observed; this process was energy-dependent as it could be prevented totally by azide or dinitrophenol (DNP). This direct demonstration of separable steps, including highly selective binding and acceptor-mediated internalization, is reconcilable with the unique potency and the multiphasic inhibitory action of BoNT on transmitter release, as shown electrophysiologically.     

A point mutation in the neu oncogene mimics ligand induction of receptor aggregation

The rat neu gene, which encodes a protein closely related to the epidermal growth factor receptor, is a proto-oncogene that can be converted into an oncogene by a point mutation. Both genes encode proteins with a relative molecular mass of 185,000 but the question of why the neu gene product, p185neu, is oncogenic, whereas the product of c-neu, p185c-neu, is not, remains unanswered. The proteins have several features common to the family of tyrosine kinase growth-factor receptors, including cysteine-rich external domains, a hydrophobic transmembrane region and a cytoplasmic tyrosine kinase domain. The oncogenic p185neu differs from p185c-neu by an amino-acid substitution in the transmembrane region of the glycoprotein: this replacement of valine by glutamic acid at position 664 induces increased intrinsic tyrosine kinase activity which is associated with transformation. Many glycoproteins with charged amino acids in the transmembrane region exist as multimeric complexes at the plasma membrane. We have therefore investigated the association state of both products of the neu gene and show that the oncoprotein p185neu is organized at the plasma membrane primarily in an aggregated form, but that p185c-neu is not. Induction of an aggregated state may mimic aspects of ligand-induced receptor aggregation resulting in enzymatic activation that leads to cellular transformation.     

The inner jet of an active galactic nucleus as revealed by a radio-to-gamma-ray outburst

Blazars are the most extreme active galactic nuclei. They possess oppositely directed plasma jets emanating at near light speeds from accreting supermassive black holes. According to theoretical models, such jets are propelled by magnetic fields twisted by differential rotation of the black hole's accretion disk or inertial-frame-dragging ergosphere. The flow velocity increases outward along the jet in an acceleration and collimation zone containing a coiled magnetic field. Detailed observations of outbursts of electromagnetic radiation, for which blazars are famous, can potentially probe the zone. It has hitherto not been possible to either specify the location of the outbursts or verify the general picture of jet formation. Here we report sequences of high-resolution radio images and optical polarization measurements of the blazar BL Lacertae. The data reveal a bright feature in the jet that causes a double flare of radiation from optical frequencies to TeV gamma-ray energies, as well as a delayed outburst at radio wavelengths. We conclude that the event starts in a region with a helical magnetic field that we identify with the acceleration and collimation zone predicted by the theories. The feature brightens again when it crosses a standing shock wave corresponding to the bright 'core' seen on the images.