Interactions of the neurotoxic amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine with monoamine oxidases.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a thermal breakdown product of a meperidine-like narcotic used by drug abusers as a heroin substitute, produces Parkinsonian symptoms in humans and primates. The nigrostriatal toxicity is not due to MPTP itself but to one or more oxidation products resulting from the action of monoamine oxidase (MAO) on this tertiary allylamine. Both MAO A and B catalyse the oxidation of MPTP to the 1-methyl-4-phenyl-2,3-dihydropyridinium species (MPDP+), which undergoes further oxidation to the fully aromatic 1-methyl-4-phenylpyridinium species (MPP+). These bio-oxidations are blocked by selective inhibitors of MAO A and B. Additionally, MPTP, MPDP+ and MPP+ are competitive inhibitors of MAO A and B. The A form of the enzyme is particularly sensitive to this type of reversible inhibition. Both MAO A and B also are irreversibly inactivated by MPTP and MPDP+, but not by MPP+. This inactivation obeys the characteristics of a mechanism-based or 'suicide' process. The inactivation, which is accompanied by the incorporation of radioactivity from methyl-labelled MPTP, is likely to result from covalent modification of the enzyme.     

Site recognition by protein-primed T cells shows a non-specific peptide size requirement beyond the essential residues of the site. Demonstration by defining an immunodominant T site in myoglobin.

In previous studies, six T sites within myoglobin (Mb) were localized. To define precisely the boundaries of the T sites, a new approach is introduced and applied here to the T site residing within residues 107-120 of Mb. Two sets of peptides were synthesized. One set represents a stepwise elongation by one-residue increments of the Mb sequence. The other set represents an identical stepwise addition of one-residue increments of the Mb sequence, but which were extended by additional unrelated (nonsense) residues to a uniform size of 14 residues. The longer peptides (nonsense-extended) usually gave higher proliferative responses than did their shorter counterparts having the same Mb region. Thus a minimum peptide size is required for optimal T-cell stimulation. The T site subtends, in three high-responder mouse strains, residues 109-119 or 110-120, depending on strain, and, in three low-responder strains, maps to residues 108-120. Thus, in this case, the T site coincides with the site of B-cell recognition and resides in a small discrete surface region of the protein chain.     

INCIDENTAL MORTALITY OF NORTHERN SEA LIONS IN SHELIKOF STRAIT, ALASKA

The incidental catch of northern sea lions ( Eumetopias jubatus ) in the walleye pollock ( Theragra chalcogramma ) joint-venture fishery in Shelikof Strait, Alaska, was studied during 1982–1984 to assess the nature and magnitude of the catch. Data were obtained by placing U.S. observers on foreign processing vessels. Dead sea lions recovered from trawl nets were counted, sexed and measured, teeth were removed for age determination by dental laminae; and stomach contents were analyzed. Although the fishery has continued to expand both in number of boats and estimated total catch (74,136 metric tons [t] in 1982 to 171,539 t in 1984), the estimated incidental catch of northern sea lions has declined (ranging from 958 to 1,436 in 1982, 216 to 324 in 1983 and 237 to 355 in 1984). Of the sea lions processed, 73 percent were caught between 2000 and 0500 h, probably during net retrieval. Most caught sea lions were females ranging in age from 1–25 yr with a mean age of 6.43 yr; 79 percent of the females were sexually mature and probably part of the reproducing population. Males had a mean age of 4.8 yr and only 12 percent were old enough to obtain and defend territories. Analysis of stomach contents showed that the sea lions consumed pollock the same size as that taken by the commercial fishery. The impact of the incidental catch on the Gulf of Alaska sea lion population is unknown.     

Paleolimnology of the Peten Lake District,Guatemala

Long-term changes of sedimentary particle-size distribution in two tropical lowland lakes were compared with changes of human population sizes, estimated archaeologically, in the drainage basins. Mean particle size of silt and clay fractions (<64 µm) varied between 3 and 15 µm. High positive skewness and kurtosis of the distributions were associated with smaller particle sizes; hence small mean size resulted from greater influx of small particles while influx of larger particles was probably constant. An inverse correlation between mean particle size and human population size is interpreted to mean that disturbance-induced erosion results in delivery of very fine inorganic particles at higher rates. Within any one basin, particle-size stratigraphy is more precisely related to archaeological time periods than is pollen stratigraphy. An absolute chronology still eludes us, owing to the failure of ¹⁴C dating of calcareous, colluvial sediments, but our relative chronology is now more precise than before. If certain assumptions about past hydrologic relations can be met, particle-size analysis is a way of comparing the histories of geographically very different lakes, including lakes from tropical, temperate, and arctic regions.     

Interaction of Agromyces ramosus with Other Bacteria in Soil

Agromyces ramosus occurs in very high numbers in most soils and, based on studies of laboratory isolates, does not require host cells for growth. Nevertheless, it attacked and destroyed most of the gram-positive and gram-negative bacterial species tested as possible host organisms. A. ramosus also attacked and destroyed Saccharomyces cerevisiae. The possibility of attack on fungi was unclear. Among the bacteria serving as hosts were the important soil species Azotobacter vinelandii, Rhizobium leguminosarum, Rhizobium meliloti, and Agrobacterium tumefaciens. Dead cells were not attacked. A. vinelandii cysts were attacked but left unharmed. To some extent, A. vinelandii seemed to survive this attack by encysting. Attack by A. ramosus occurred in natural soil and over a broad range of nutritional levels in laboratory media. The attack did not seem to be a means for obtaining an increased supply of commonly available nutrients. Instead, it seemed to be a means of obtaining something produced, perhaps in small amounts, by a variety of organisms, but not by all organisms. Several types of culture filtrates were tested for activity. The filtrates neither stimulated nor inhibited the growth of A. ramosus or the host organisms. The availability of catalase activity in host organisms did not seem to be involved. It is not known whether the attack by Agromyces ramosus in soil can be manipulated to cause a decrease in numbers of Agrobacterium tumefaciens or other pathogens without simultaneously depressing the numbers of beneficial organisms in this habitat.     

Relationship between lactic acid concentration and bacterial spoilage in ground beef.

Lactic acid concentration correlated with organoleptic spoilage of refrigerated, coarsely ground beef stored in casings with low oxygen permeability. The samples were assayed over time for lactic acid concentration, total aerobic plate count, percentage of gram-positive organisms, and pH. Lactic acid increased in all samples, as did the bacterial counts and percentage of gram-positive organisms in the total microflora, the latter representing an increase in the lactic acid-producing bacteria. pH was found to decrease in all samples, with the smallest decrease in pH being observed in the meat sample which maintained the lowest proportion of gram-positive organisms. With samples evaluated by a sensory panel, lactic acid levels were found to correlate inversely with odor acceptability.     

Sequence analysis of mitochondrial DNA in a mouse cell line resistant to chloramphenicol and oligomycin.

A mouse L-cell line, designated 111-OB3, is described which is resistant to two drugs, chloramphenicol and oligomycin. The cells contain two types of mitochondrial DNA molecules, in roughly equal proportions, which differ in that one is cleaved by endonuclease EcoRI at a novel site within the coding sequence for subunit 6 of the mitochondrial ATPase (ATPase-6). Sequence analysis reveals that the cleavage site was created by a single transversion which predicts a replacement of valine in the wild-type ATPase-6 by glutamic acid. The replacement occurs in a hydrophobic amino acid sequence which is highly conserved in mouse, human, and bovine proteins. The position of the replacement is similar to a substitution observed in one class of yeast mutants resistant to oligomycin. Both of the mitochondrial DNA molecules in 111-OB3 also have a single nucleotide change in the gene encoding the large (16S) rRNA. These observations are consistent with the hypothesis that oligomycin resistance in mammalian cells can be cytoplasmically determined and can result from alterations in ATPase-6. The appearance of the mutation before selection in oligomycin suggests a model for the origin of mitochondrial mutations in mammalian cells.     

Active transport of l-aspartic acid in Neurospora crassa

Transport of l-aspartic acid in Neurospora crassa conidia is shown to be mediated by neutral and general amino acid transport systems. The transport activity is dependent on pH and results in accumulation of l-aspartic acid against a gradient. Mutants deficient in transport of l-aspartic acid are described.     

Fragments of human γG immunoglobulins produced by a porcine pancreatic esterase

The effect of a porcine pancreatic esteroproteolytic enzyme on human IgG has been described. A sequential breakdown of the molecule occurs. The first cleavage results in the formation of an F′c fragment together with an F(ab)₂ fragment. A subsequent proteolysis of the F(ab)₂ fragment liberates two Fab fragments. Each fragment has been characterized by its antigenic properties, molecular weight, and sulfhydryl content.