Cell lineage analysis by intracellular injection of fluorescent tracers

Cell lineages during development of the leech are revealed by injection of a fluorescent peptide, rhodamine-D-peptide, into identified embryonic cells. Use of this peptide together with a nuclear stain showed a stereotypic cleavage pattern of stem cells and their progeny. Combined injection of rhodamine-D-peptide and pronase demonstrated the arrest of stem cell production in the pronase-injected teloblast.     

Double-labeled metabolic maps of memory

The physical changes representing a memory are believed to be localized to specific neurons, widely distributed in multiple parallel pathways in the brain. 2-Fluorodeoxyglucose, labeled with two discriminable radioactive tracers, was used to construct quantitative metabolic maps in split-brain cats during a visual task. One side of the brain served to estimate the metabolic variability of nonspecific influences. The other side was used to map metabolic changes related to the presence of previously learned visual cues, as well as changes related to nonspecific influences, in the same periods of time. When the two sides were compared, between 5 million and 100 million neurons (depending upon the significance level selected) were identified in which activity increased during presentation of the familiar cues. The wide distribution of these neurons throughout the brain is compatible with prior evidence of a distributed memory system. However, the large number of neurons involved is difficult to reconcile with theories in which individual neurons are dedicated to specific memories.     

O2 activation by nonheme iron complexes: A monomeric Fe(III)-Oxo complex derived from O2

Iron species with terminal oxo ligands are implicated as key intermediates in several synthetic and biochemical catalytic cycles. However, there is a dearth of structural information regarding these types of complexes because their instability has precluded isolation under ambient conditions. The isolation and structural characterization of an iron(III) complex with a terminal oxo ligand, derived directly from dioxygen (O2), is reported. A stable structure resulted from placing the oxoiron unit within a synthetic cavity lined with hydrogen-bonding groups. The cavity creates a microenvironment around the iron center that aids in regulating O2 activation and stabilizing the oxoiron unit. These cavities share properties with the active sites of metalloproteins, where function is correlated strongly with site structure.     

Early results from the infrared astronomical satellite

For 10 months the Infrared Astronomical Satellite (IRAS) provided astronomers with what might be termed their first view of the infrared sky on a clear, dark night. Without IRAS, atmospheric absorption and the thermal emission from both the atmosphere and Earthbound telescopes make the task of the infrared astronomer comparable to what an optical astronomer would face if required to work only on cloudy afternoons. IRAS observations are serving astronomers in the same manner as the photographic plates of the Palomar Observatory Sky Survey; just as the optical survey has been used by all astronomers for over three decades, as a source of quantitative information about the sky and as a "roadmap" for future observations, the results of IRAS will be studied for years to come. IRAS has demonstrated the power of infrared astronomy from space. Already, from a brief look at a miniscule fraction of the data available, we have learned much about the solar system, about nearby stars, about the Galaxy as a whole and about distant extragalactic systems. Comets are much dustier than previously thought. Solid particles, presumably the remnants of the star-formation process, orbit around Vega and other stars and may provide the raw material for planetary systems. Emission from cool interstellar material has been traced throughout the Galaxy all the way to the galactic poles. Both the clumpiness and breadth of the distribution of this material were previously unsuspected. The far-infrared sky away from the galactic plane has been found to be dominated by spiral galaxies, some of which emit more than 50 percent and as much as 98 percent of their energy in the infrared-an exciting and surprising revelation. The IRAS mission is clearly the pathfinder for future missions that, to a large extent, will be devoted to the discoveries revealed by IRAS.     

The complete primary structure of protein kinase C--the major phorbol ester receptor

Protein kinase C, the major phorbol ester receptor, was purified from bovine brain and through the use of oligonucleotide probes based on partial amino acid sequence, complementary DNA clones were derived from bovine brain complementary DNA libraries. Thus, the complete amino acid sequence of bovine protein kinase C was determined, revealing a domain structure. At the amino terminal is a cysteine-rich domain with an internal duplication; a putative calcium-binding domain follows, and there is at the carboxyl terminal a domain that shows substantial homology, but not identity, to sequences of other protein kinase.     

T cell activation by lipopeptide antigens

Unlike major histocompatibility proteins, which bind peptides, CD1 proteins display lipid antigens to T cells. Here, we report that CD1a presents a family of previously unknown lipopeptides from Mycobacterium tuberculosis, named didehydroxymycobactins because of their structural relation to mycobactin siderophores. T cell activation was mediated by the alphabeta T cell receptors and was specific for structure of the acyl and peptidic components of these antigens. These studies identify a means of intracellular pathogen detection and identify lipopeptides as a biochemical class of antigens for T cells, which, like conventional peptides, have a potential for marked structural diversity.     

Infrared echoes near the supernova remnant Cassiopeia A

Two images of Cassiopeia A obtained at 24 micrometers with the Spitzer Space Telescope over a 1-year time interval show moving structures outside the shell of the supernova remnant to a distance of more than 20 arc minutes. Individual features exhibit apparent motions of 10 to 20 arc seconds per year, independently confirmed by near-infrared observations. The observed tangential velocities are at roughly the speed of light. It is likely that the moving structures are infrared echoes, in which interstellar dust is heated by the explosion and by flares from the compact object near the center of the remnant.     

Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease

The sirtuins are members of the histone deacetylase family of proteins that participate in a variety of cellular functions and play a role in aging. We identified a potent inhibitor of sirtuin 2 (SIRT2) and found that inhibition of SIRT2 rescued alpha-synuclein toxicity and modified inclusion morphology in a cellular model of Parkinson's disease. Genetic inhibition of SIRT2 via small interfering RNA similarly rescued alpha-synuclein toxicity. Furthermore, the inhibitors protected against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson's disease. The results suggest a link between neurodegeneration and aging.