Experimental erythrocyte autoantibodies. V. Induction and suppression of red blood cell autoantibodies in mice injected with rat bromelain-treated red blood cells

Mice injected with rat red blood cells (RBC), or rat bromelain-treated (brom) RBC, produce RBC autoantibodies and suppressor cells that specifically inhibit the autoimmune response without inhibiting the net production of antibodies against rat RBC. It has been investigated whether suppressor cells induced by injections of rat RBC are effective in preventing autoantibody production induced by rat brom RBC and vice versa. Autoantibodies were induced in C3H mice by weekly ip injections, each 0.2 ml, of a 6% suspension of rat RBC or rat brom RBC. Autoantibody production was assayed using Coombs' test. Suppressor cells were present in the spleens of mice positive in Coombs' tests and were shown by intravenous injections of 40 X 10(6) viable cells per mouse into untreated syngeneic mice 18 hr before the first injection of rat RBC or rat brom RBC. Autoantibodies eluted from mice positive in Coombs' tests after injections of rat RBC or brom RBC were absorbed by either type of rat RBC but not by RBC from sheep. This suggests that rat RBC and rat brom RBC display antigens that are similar, if not identical, to autoantigens on the mouse RBC. Spleen cells from mice injected with rat RBC suppressed autoantibodies induced by both rat RBC and rat brom RBC. In contrast, spleen cells from mice injected with rat brom RBC suppressed autoantibodies induced by rat brom RBC but not those induced by unmodified rat RBC. This differential suppression may be due to the removal from rat RBC, by bromelain, of a suppressor site and/or autoantigens of some specificities. Thus rat brom RBC may not induce the total range of specificities of autoantibodies, and of suppressor cells, induced by rat RBC.     

Using the therapy and enhancement distinction in law and policy

In a first major study, the UK’s Royal Society found that 76% of people in the UK are in favour of therapeutic germline genomic editing to correct genetic diseases in human embryos, but found there was little appetite for germline genomic editing for non-therapeutic purposes. Assuming the UK and other governments acted on these findings, can lawmakers and policymakers coherently regulate the use of biomedical innovations by permitting their use for therapeutic purposes but prohibiting their use for enhancement purposes? This paper examines the very common claim in the enhancement literature that the therapy v enhancement distinction does little meaningful work in helping us think through the ethical issues, a claim that has significant implications for these lawmakers and policymakers who may wish to regulate genomic editing techniques to reflect the findings of this important study. The focus of this paper is on germline genomic editing as one of the main themes in this special issue.     

A biogeographical perspective on ecological systems: some personal reflections

During my graduate studies, I characterized patterns of geographical distribution and taxonomic differentiation in birds of the West Indies, which suggested that species undergo phases of expansion and contraction similar to the taxon cycles that E. O. Wilson had described for Melanesian ants. Fieldwork in the early 1970s with George Cox confirmed that these phases were associated with variation in habitat distribution and abundance on individual islands, tying together local ecology and biogeography. Because taxon‐cycle stage was independent of taxonomic or ecological relationships among birds of the West Indies, George and I postulated that whether a species was in a phase of expansion or contraction reflected the outcome of coevolved relationships with antagonists, including pathogens. The taxon cycle concept had a cool reception initially, but subsequent phylogeographical analyses, beginning in the early 1990s with Eldredge Bermingham, provided a time scale that confirmed the relationship between taxon cycle stage and the relative age of the most recent population expansion. The discrete nature of islands allows one to visualize taxon cycles in island systems, but the principle should apply in a continental biota as well. The absence of strong phylogenetic effects in distribution and abundance is consistent with evolutionary lability caused by coevolutionary outcomes with specialized antagonists. Related species appear to compete for resources on a more‐or‐less equal footing across a broad range of environments, and their distribution at any particular time is likely to be determined primarily by their relationships with pathogens, among other antagonists. This model of distribution and abundance within a regional community is consistent with much of what we know about the interactions between pathogens and their host populations, but testing the model will require the development of a new research programme focused on endemic pathogen effects in natural communities.     

The influence of different nutrient levels on insect-induced plant volatiles in Bt and conventional oilseed rape plants

Transgenic Bt (expressing the cry1Ac endotoxin gene) and conventional oilseed rape plants grown in different soils were used to study nutrient uptake and emission of volatiles after herbivore damage. All plants were greenhouse-grown in soils representing low-, medium- and high-nutrient levels. The concentrations of N, P, K, Mg and Zn were significantly affected by the transgene, while the main effect of soil type appeared in N, P, Ca, Mg, B, Mn and Zn concentrations in the plants. Plants with four to five leaves were infested with the third instar larvae of Bt-susceptible Plutella xylostella for 48 h, and samples of volatiles were collected and analysed. In the first experiment, the soil nutrient level had a significant effect on the emissions of (Z)-3-hexen-1-ol, (Z)-3-hexenyl acetate, hexyl acetate, (E)-4,8-dimethyl-1,3,7-non-atriene (DMNT), beta-elemene, gamma-bisabolene, alpha-bisabolene and (E)-nerolidol. The induction of these volatiles was significantly higher in infested conventional plants grown at a high-soil nutrient level compared to infested conventional plants at a low-soil nutrient level. In the second experiment, the soil nutrient level had a significant effect on the emissions of (Z)-3-hexen-1-ol, (Z)-3-hexenyl acetate and beta-elemene and, again, this was significantly higher in infested conventional plants grown at high-soil nutrient levels in comparison with infested plants at a low-soil nutrient level. In both experiments, the transgene effect was significant on the emissions of DMNT and (E,E)-alpha-farnesene. The differences in emissions between the two separate experiments suggest that growth conditions (particularly daylength) and sampling procedure may affect the ratio of compounds detected in the emission blend, even though the response to herbivory, nutrient availability and the transgene were similar.     

Characterization of Hypericum perforatum L. (St. John’s wort) macerates prepared with different fatty oils upon processing and storage

Hypericum perforatum L. (St. John’s wort, SJW) is a traditional medicinal plant with a long history of pharmaceutical application. Today, besides formulations based on hydro-alcoholic extracts, lipophilic SJW preparations are widely used in phytomedicine e.g. for the symptomatic treatment of minor inflammations of the skin and subcutaneous tissue disorders. In the present study, SJW extracts were obtained with twelve different fatty oils according to a standardized protocol. In order to evaluate and compare the resulting macerates, a set of analytical parameters was chosen: the phytochemical profile of SJW oil extracts comprising acylphloroglucinol derivatives, flavonols, biflavones and naphthodianthrones was assessed using UHPLC-DAD and UV/VIS-spectroscopic methods Furthermore, overall appearance was monitored applying the CIE L*a*b* color system. Depending on the type of oil applied for extraction, a*-values, which are a measure of red color hues, ranged from 50.3 ± 0.2 (almond oil) to −3.8 ± 0.3 (macadamia nut oil). Considering total hypericin contents, extraction with almond oil also brought about highest amounts (5.5 ± 0.21 mg/100 g). In contrast, preparations with macadamia nut oil resulted in highest contents of hyperforin and adhyperforin, whereas a semi-synthetic extractant composed of medium-chain triglycerides (MCT) revealed highest yields of flavonoids, i.e. quercetin, kaempferol and I3, II8-biapigenin. Since the phytochemical composition and the corresponding specific characteristics of SJW oil preparations markedly differed, tailor-made SJW extracts may be prepared by systematic adaption of the manufacturing conditions, including the choice of a specific fatty oil. Additionally, SJW oil extracts were stored under different temperature (5 °C, 20 °C, 50 °C) and light (artificial light, darkness) regimes over a period of six months to evaluate their respective storage stability. For maximizing the retention of the investigated plant secondary metabolites in the corresponding oil extracts, cold storage (5 °C) under the exclusion of light is recommended.     

Southern Trauma: Revisiting Caste and Class in the Mississippi Delta

Two classic ethnographies, Hortense Powdermaker's After Freedom: A Cultural Study in the Deep South and John Dollard's Caste and Class in a Southern Town , contributed to a "master narrative" of the Mississippi Delta and the South that viewed class largely through the lens of race. Their work contributed to the community studies and culture and personality traditions and became part of the public discourse of race in the United States. This article examines the institutional and theoretical frameworks within which they worked. We focus on three aspects of their work: (1) their definition of class that left race as the only salient social divide; (2) their portrayal of middle- and upper-class statements as normative; and (3) their uncritical use of data from elsewhere in the South to interpret their Indianola data. We report the events at the Yale Institute of Human Relations that led Dollard to publish before Powdermaker.     

Cadmium(II)-113 NMR studies of the mechanism of metal ion activation of yeast enolase

Yeast enolase binds one mole of 113Cd2+ per subunit at a site that consists of all oxyligands in a distorted octahedral environment. This "conformational" metal ion's environment undergoes further distortion on addition of substrate/product or analogs. At pH's below the optimum value the shifted resonance tends to break up into several, suggesting the existence of several slowly exchanging intermediate forms. At acid pH's, on addition of one additional mole/subunit of 113Cd2+, which greatly increases catalysis, "conformational" resonance(s) further broadens, suggesting that the second, "catalytic" metal ion increases the rates of interconversion between "conformational" species. At more alkaline pH's, near the optimum pH, the "conformational" peak is sharpened, which suggests that very fast interconversion is occurring. The position of the "catalytic" metal ion resonance also suggests all oxyligands in a distorted octahedral geometry. The "catalytic" resonance is often broadened to the point where it cannot be seen, suggesting rapid changes in its geometry due to interconversion of substrate and product.     

Circular dichroism (CD) studies on yeast enolase: activation by divalent cations

The effect of divalent cations on the near ultraviolet circular dichroism (CD) spectrum of yeast enolase showed that calcium, magnesium, and nickel ions produced identical changes. This was interpreted as indicating that the cations bound to the same sites on the enzyme and produced identical changes in tertiary structure. There was no effect of magnesium ion on the far ultraviolet spectrum. Evidently magnesium ion has no effect on the secondary structure. Substrate bound to the enzyme when the above cations were present although calcium permits no enzymatic activity. The CD spectral difference produced by the substrate was nearly the reverse of that produced by the metal ions. Glycolic acid phosphate, a competitive inhibitor lacking carbon-3, produced no effect, indicating carbon-3 was necessary for the CD spectral changes. The CD and visible absorption spectra of nickel and cobalt bound to various sites on the enzyme showed that the binding sites were octahedral or distorted octahedral in coordination and that the ligands appeared to be oxyligands: water molecules, hydroxyl or carboxyl groups. Examination of the effects of substrate and two compounds thought to be "transition state analogues" showed that these perturbed the "conformational" sites of the enzyme. The "catalytic" and "inhibitory" sites did not appear to be very CD active.