Effect of pH on MHC class II-peptide interactions.

The effect of pH on class II-peptide interactions has been analyzed using several mouse (IAd, IAk, IEd, IEk) and human (DR1, DR5, DR7) MHC specificities, and eight different class II-restricted determinants. In direct binding assays, acidic conditions led to increased binding capacity for many class II-peptide combinations. IE molecules seemed to bind optimally around pH 4.5, whereas IA molecules displayed binding optima in the 5.5 to 6.5 range. In contrast, the DR molecules studied were, in most cases, affected only marginally by pH changes in the 4.5 to 7.0 range. Despite these apparent isotype-specific trends, no general rule could be formulated, because even for the same class II molecules, the binding capacity could be increased for many peptides when the binding was performed under acidic conditions, was unaffected for some, and even decreased for others. The mechanisms responsible for this complex behavior were analyzed in more detail by kinetic and equilibrium analysis of three different class II-peptide combinations (IAd/OVA 323-339, IAk/HEL 46-61, and DR1/HA 307-319). It was found that acidic pH conditions could affect both on and off rates for class II-peptide complexes. Depending on the net balance of these effects, either increases, decreases, or no effect on overall affinities at equilibrium were detected. In the case of IAd/OVA 323-339, it was also found that acidic conditions influenced the binding capacity of class II molecules by increasing the fraction of sites available for peptide binding, presumably by favoring dissociation of endogenously bound, acid-sensitive peptides.     

Spirits and spiritist therapy in Southern Brazil: A case study of an innovative,syncretic healing group

This paper examines the treatment of patients by a group of Spiritist healers in southern Brazil. After describing and analyzing a healing session, the practices are shown to be deviant from conventional Spiritism in two directions: (1) they employ a technique, called apometry, that they claim makes possible the transportation of a part of the patient's body to the astral world where it is treated by disincarnate doctors who do past life regressions; and (2) although a conventional Spiritist disobsession is performed, the healers invoke rival Afro-Brazilian spirits who often are shown to have caused the patient's symptoms.Building on the work of Csordas (1983), 1 hypothesize that the discourse employed by the healers moves the patient to a new reality or phenomenological world in which s/he is healed not in the sense of being restored to the state in which s/he existed prior to the onset of illness, but in the sense of being rhetorically moved into a state dissimilar from both pre-illness and illness reality... (Csordas 1983:346). The new state, in this case, is the world of Spiritism. Unlike the Catholic Pentecostals Csordas studied who already were members of a primary group of believers, however, the patients treated by the Brazilian healers are mostly unaffiliated individuals who face the increasing uncertainty and insecurity of life in disorganized, anomic, urban Brazil. By encompassing modern science on the one hand, and aspects of the Afro-Brazilian traditions on the other, this healing group appeals to the often distraught white middle and lower-middle classes, providing them with therapeutic meaning that in many cases leads to healing, conversion, and the sense of security and safety that often accompanies identifying with and belonging to a religious group.     

Inhibition of cerebral protein kinase activity and cyclic AMP-dependent ribosomal-protein phosphorylation in experimental hyperphenylalaninaemia

Studies were carried out to elucidate the mechanisms underlying the diminished phosphorylation of cerebral ribosomal protein in experimental hyperphenylalaninaemia [Roberts & Morelos (1980) Biochem. J.190, 405-419]. Administration of N(6),O(2)'-dibutyryl cyclic AMP or 3-isobutyl-1-methylxanthine, which increased phosphorylation of the S6 protein of cerebral 40S ribosomal subunits in control infant rats, did not counteract the decreased phosphorylation of this ribosomal protein resulting from intraperitoneal administration of a loading dose of l-phenylalanine. N(2),O(2)'-Dibutyryl cyclic GMP had no effect on cerebral ribosomal-protein phosphorylation in either control or hyperphenylalaninaemic animals. The phenylalanine-induced decrease in ribosomal-protein phosphorylation was associated with decreased protein kinase activity in cerebral cytosolic and microsomal preparations. However, the maximal protein kinase response to cyclic AMP added in vitro was unaltered by prior administration of phenylalanine in vivo. The heat-stable protein inhibitor of cyclic AMP-dependent protein kinases decreased the activity of these enzymes by about 90% and eliminated the phenylalanine-induced difference in protein kinase activity in the absence of added cyclic AMP. Intracisternal administration of doses of dibutyryl cyclic AMP or 3-isobutyl-1-methylxanthine which increased the cyclic AMP-dependent protein kinase activity ratio in control infant rats was without effect on this index in phenylalanine-treated animals. Dibutyryl cyclic GMP had no effect on the protein kinase activity ratio in either group of animals. These results suggest that inhibition of cerebral cyclic AMP-dependent protein kinases by abnormally high concentrations of phenylalanine may contribute to the decrease in cerebral ribosomal-protein phosphorylation in experimental hyperphenylalaninaemia.     

Analysis in vivo of translational mutants of the rIIB cistron of bacteriophage T4

We have mapped the mutants isolated by Nelson et al. (1981) that reduce the amount of rIIB protein synthesized during bacteriophage T4 infection of Escherichia coli B and characterized their rIIB expression in vivo. These mutants fall into four distinct groups in terms of mapping and phenotype. We have located the probable site of each mutation on the DNA sequence. We have also analyzed a number of other mutations near the initiating AUG of rIIB with respect to their rIIB expression. In some of these mutants, ribosomal recognition of the wild-type initiating AUG is precluded and so initiation occurs at a different AUG, which, in some instances, we have identified.     

Calmodulin in mammalian nerve

Calmodulin, a calcium-dependent regulatory protein has been isolated from mammalian nerve. The protein has similarities to the calcium-binding protein earlier shown to be transported at a fast rate in the nerve fibers. The implication is that calmodulin, which has been shown to be involved in various key cellular processes, may have a relation to axoplasmic transport.     

The induction of antigenic changes in a teratocarcinoma stem cell line (F9) by retinoic acid

Treatment of embryonal carcinoma cells F9 with retinoic acid results in the appearance of epithelioid cells resembling endoderm which synthesize basement membrane protein and plasminogen activator. Concomitant with the appearance of these properties of differentiated cells, the epithelial cells cease to express SSEA-1, an antigenic determinant characteristic of teratocarcinoma stem cells and early mouse embryos. Our evidence indicates that the phenotypic changes that accompany retinoic acid treatment of embryonal carcinoma cells are irreversible and a consequence of the differentiation of the cells into endoderm.     

Context Effects on Nonsense Codon Suppression in ESCHERICHIA COLI

The influence of mRNA context on nonsense codon suppression has been studied by suppression measurements at one site in the Escherichia coli trpE gene and at two sites in the trpA gene. The ratio of suppression efficiencies of amber and ochre codons at each site (homotopic pairs) has been compared using ochre suppressing derivatives of tRNATyr. This ratio is independent of differential effects of the inserted amino acid on enzyme function. We have found that mRNA context can change the ratio of suppression efficiencies of homotopic nonsense codons at the three sites in the trp gene system over a ten-fold range. The causes of such variation, and, in particular the effect of certain adjacent nucleotides on nonsense codon suppression are considered.