Pertussis toxin inhibits EGF-, phorbol ester- and insulin-stimulated DNA synthesis in BALB/c3T3 cells: evidence for post-receptor activation of Gi alpha

The contribution of the GTP-binding protein, Gi, to EGF, phorbol dibutyrate (PdBu)-, and insulin-stimulated DNA synthesis was examined in BALB/c3T3 cells. Pertussis toxin inhibited DNA synthesis by each agonist, particularly at suboptimal agonist concentrations, but the inhibition could be partially overcome with higher agonist concentrations and combinations of these agonists. This suggested that (1) some, but not all, of the mitogenic signals for all three agonists were transduced by Gi (2) Gi may be activated by post-receptor mechanisms involving protein kinase C. Gi alpha-specific antibodies and ADP-ribosylation by pertussis toxin using 32P-NAD each labelled a single protein band, representing one or more species of Gi alpha. Pertussis toxin treatment increased the synthesis of Gi alpha. These results are discussed in relation to possible direct effects of Gi alpha on nuclear control during division.     

Poliovirus Adsorption by 34 Minerals and Soils

The adsorption of radiolabeled infectious poliovirus type 2 by 34 well-defined soils and mineral substrates was analyzed in a synthetic freshwater medium containing 1 mM CaCl₂ and 1.25 mM NaHCO₃ at pH 7. In a model system, adsorption of poliovirus by Ottawa sand was rapid and reached equilibrium within 1 h at 4°C. Near saturation, the adsorption could be described by the Langmuir equation; the apparent surface saturation was 2.5 × 10⁶ plaque-forming units of poliovirus per mg of Ottawa sand. At low surface coverage, adsorption was described by the Freundlich equation. The soils and minerals used ranged from acidic to basic and from high in organic content to organic free. The available negative surface charge on each substrate was measured by the adsorption of a cationic polyelectrolyte, polydiallyldimethylammonium chloride. Most of the substrates adsorbed more than 95% of the virus. In general, soils, in comparison with minerals, were weak adsorbents. Among the soils, muck and Genesee silt loam were the poorest adsorbents; among the minerals, montmorillonite, glauconite, and bituminous shale were the least effective. The most effective adsorbents were magnetite sand and hematite, which are predominantly oxides of iron. Correlation coefficients for substrate properties and virus adsorption revealed that the elemental composition of the adsorbents had little effect on poliovirus uptake. Substrate surface area and pH, by themselves, were not significantly correlated with poliovirus uptake. A strong negative correlation was found between poliovirus adsorption and both the contents of organic matter and the available negative surface charge on the substrates as determined by their capacities for adsorbing the cationic polyelectrolyte, polydiallyldimethylammonium chloride.     

Nutritional requirements for conidial germination and hyphal growth of Beauveria bassiana

Nutritional requirements for germination and growth of the entomopathogenic fungus Beauveria bassiana are not complex. For germination to occur, a utilizable source of carbon must be present; however, a nitrogen source is needed for continued hyphal growth, otherwise lysis ensues. Compounds that can serve as utilizable carbon-energy sources for germination include glucose, N-acetylglucosamine, glucosamine, chitin, starch, lanolin, hydrocarbons in crude oil, and some longer-chain fatty acids. Both organic and inorganic sources of nitrogen are readily utilized for growth. Conidia undergo active metabolism soon after being placed in a suitable growth medium, indicating that conidia are released from their state of dormancy several hours before emergence of the germ tube can be observed. Because of the nutritional versatility of B. bassiana, this fungus should be able to survive and be infective in several types of natural environments.     

Analysis of neonatally induced tolerance of H-2 alloantigens

There is a considerable amount of evidence, confirmed and extended by our studies, in favor of clonal deletion of alloantigen-reactive cells in neonatally induced transplantation tolerance. We have demonstrated in adult mice bearing long-standing skin allografts that lymphocytes specifically reactive with the tolerated H-2 alloantigens are undetectable by mixed lymphocyte and graftversus-host reactions, and in cell-mediated lympholysis. In addition, lymphoid cells capable of suppressing the reactivity of syngeneic normal lymphocytes in these assays similarly escape detection. Moreover, putative precursors of T cells specific for the tolerated antigens cannot be activated polyclonally with concanavalin A (Con A), nor can they be identified among thymocytes ofH-2-tolerant mice. Since the tolerant state can be adoptively transferred with lymphohematopoietic cells to adult, syngeneic mice, we infer that transplantation tolerance is maintained by an active process that achieves specific clonal deletion at an early stage in the ontogeny of alloreactive T lymphocytes.     

Non-accidental injury in children: what we do in Derby.

A scheme for dealing with cases of non-accidental injury in children in the Derby clinical area has been operating since 1971. A stable team of doctors, policemen, and social workers deal with each case. The parents are told at once that battering is suspected, and the police and social services department co-operate closely in establishing the facts, supporting the family, and protecting the child. A psychiatric assessment of the parents may help social workers decide on the long-term care of the child, and the forensic physician is invaluable if the case has to go to court. The team has made three recommendations about prevention and management of these cases: a specialist social service team should be set up to deal with these children and regain the skills and knowledge lost when children''s departments were abolished in 1971; babies should be routinely weighed naked in infant welfare clinics; and juvenile courts should be able to order a psychiatric report on the parents in care proceedings.     

MAGI-1 Modulates AMPA Receptor Synaptic Localization and Behavioral Plasticity in Response to Prior Experience

It is well established that the efficacy of synaptic connections can be rapidly modified by neural activity, yet how the environment and prior experience modulate such synaptic and behavioral plasticity is only beginning to be understood. Here we show in C. elegans that the broadly conserved scaffolding molecule MAGI-1 is required for the plasticity observed in a glutamatergic circuit. This mechanosensory circuit mediates reversals in locomotion in response to touch stimulation, and the AMPA-type receptor (AMPAR) subunits GLR-1 and GLR-2, which are required for reversal behavior, are localized to ventral cord synapses in this circuit. We find that animals modulate GLR-1 and GLR-2 localization in response to prior mechanosensory stimulation; a specific isoform of MAGI-1 (MAGI-1L) is critical for this modulation. We show that MAGI-1L interacts with AMPARs through the intracellular domain of the GLR-2 subunit, which is required for the modulation of AMPAR synaptic localization by mechanical stimulation. In addition, mutations that prevent the ubiquitination of GLR-1 prevent the decrease in AMPAR localization observed in previously stimulated magi-1 mutants. Finally, we find that previously-stimulated animals later habituate to subsequent mechanostimulation more rapidly compared to animals initially reared without mechanical stimulation; MAGI-1L, GLR-1, and GLR-2 are required for this change in habituation kinetics. Our findings demonstrate that prior experience can cause long-term alterations in both behavioral plasticity and AMPAR localization at synapses in an intact animal, and indicate a new, direct role for MAGI/S-SCAM proteins in modulating AMPAR localization and function in the wake of variable sensory experience.