“Unblocking” Serum Activity <Emphasis Type="Italic">in vitro</Emphasis> in the Polyoma System may Correlate with Antitumour Effects of Antiserum <Emphasis Type="Italic">in vivo</Emphasis>

In a variety of tumour systems, individuals carrying progressively growing neoplasms have lymphoid cells with a specific cytotoxic effect on cultured tumour cells from the same individual^1–4. Since the sera of tumour-bearing individuals have been shown to prevent tumour cell destruction by immune lymphocytes in vitro^2,5–8 and since this serum blocking activity appears early in primary and transplant tumour development^5,7, it has been suggested that the appearance of this serum blocking activity might be responsible for the progressive growth of tumours in individuals having cytotoxic lymphocytes. Counteraction of this blocking activity would thus be of primary importance in facilitating the function of an already existing or bolstered cell-mediated immunity. The serum blocking activity might be inhibited in various ways, by preventing the formation of blocking antibody or by interfering with its action (“unblocking”), as demonstrated in Moloney sarcoma regressor sera⁹. This type of serum also has a therapeutic effect on Moloney sarcomas in vivo^10,11, which has been tentatively attributed to its unblocking activity^8,9 or, possibly, to a complement-dependent cytotoxicity¹⁰. Tumour growth in the Moloney sarcoma system, however, might be due in part to continuous recruitment of neoplastic cells by virus-induced transformation and so the therapeutic effect could be due to a virus-neutralizing serum activity^9,10.     

On the mechanism of ATP-induced shape changes in the human erythrocyte membranes: the role of ATP

In the preceding paper (Sheetz, M. and S.J. Singer. 1977. J Cell Biol. 73:638-646) it was shown that erythrocyte ghosts undergo pronounced shape changes in the presence of mg-ATP. The biochemical effects of the action of ATP are herein examined. The biochemical effects of the action of ATP are herein examined. Phosphorylation by ATP of spectrin component 2 of the erythrocyte membrane is known to occur. We have shown that it is only membrane protein that is significantly phosphorylated under the conditions where the shape changes are produced. The extent of this phosphorylation rises with increasing ATP concentration, reaching nearly 1 mol phosphoryle group per mole of component 2 at 8mM ATP. Most of this phosphorylation appears to occur at a single site on the protein molecule, according to cyanogen bromide peptide cleavage experiments. The degree of phosphorylation of component 2 is apparently also regulated by a membrane-bound protein phosphatase. This activity can be demonstrated in erythrocyte ghosts prepared from intact cells prelabeled with [(32)P]phosphate. In addition to the phosphorylation of component 2, some phosphorylation of lipids, mainly of phosphatidylinositol, is also known to occur. The ghost shape changes are, however, shown to be correlated with the degree of phosphorylation of component 2. In such experiment, the incorporation of exogenous phosphatases into ghosts reversed the shape changes produced by ATP, or by the membrane-intercalating drug chlorpromazine. The results obtained in this and the preceding paper are consistent with the proposal that the erythrocyte membrane possesses kinase and phosphates activities which produce phosphorylation and dephosphorylation of a specific site on spectrin component 2 molecules; the steady-state level of this phosphorylation regulates the structural state of the spectrin complex on the cytoplasmic surface of the membrane, which in turn exerts an important control on the shape of the cell.     

Selective inhibition of prostaglandin biosynthesis by gold salts and phenylbutazone

Gold salts and phenylbutazone selectively inhibit the synthesis of PGF_2α and PGE₂ respectively. Lowered production of one prostaglandin species is accompanied by an increased production of the other. Selective inhibition by these drugs was observed in the presence of adrenaline, reduced glutathione and copper sulphate under conditions when most anti-inflammatory compounds inhibited PGE₂ and PGF_2α syntheses equally. It is postulated that selective inhibitors may have a different mode of action and beneficial effects may be related to the endogenous ratio of PGE to PGF required for normal function.     

A web server to locate periodicities in a sequence

Summary : FT is a tool written in C++, which implements the Fourier analysis method to locate periodicities in aminoacid or DNA sequences. It is provided for free public use on a WWW server with a Java interface. Availability : The server address is http://o2.db. uoa.gr/FT Contact : shamodr@atlas.uoa.gr      

Phosphorus retention in lab and field-scale subsurface-flow wetlands treating plant nursery runoff

Constructed wetland systems built to handle nutrient contaminants are often efficient at removing nitrogen, but ineffective at reducing phosphorus (P) loads. Incorporating a clay-based substrate can enhance P removal in subsurface-flow constructed wetland systems. We evaluated the potential of crushed brick, a recycled building product, and two particle sizes of a palygorskite–bentonite industrial mineral aggregate (calcined clay) to sorb P from simulated nutrient-rich plant nursery effluent. The three substrates were screened for P sorbing behavior using sorption, desorption, and equilibration experiments. We selected one substrate to evaluate in an 8-month field trial to compare field sorption capacity with laboratory sorption capacity. In the laboratory, coarse calcined clay average sorption capacity was 497 mg kg⁻¹ and it sorbed the highest percentage of P supplied (76%), except at exposure concentrations >100 mg L⁻¹ where the increased surface area of fine calcined clay augmented its P sorption capacity. Subsurface-flow mesocosms were filled with coarse calcined clay and exposed to a four and seven day hydraulic retention time treatment. Phosphorus export was reduced by 60 to 74% for both treatments until substrate P-binding sites began to saturate during month seven. During the eight month experiment, the four and seven day treatments fixed 1273 ± 22 mg kg⁻¹ P and 937 ± 16 mg kg⁻¹ P, respectively. Sequential extractions of the P saturated clay indicated that P could desorb slowly over time from various pools within the calcined clay; thus, if the calcined clay were recycled as a soil amendment, most P released would be slowly available for plant uptake and use. This study demonstrated the viability of using coarse calcined clay as a root bed substrate in subsurface-flow treatment wetlands remediating phosphorus from plant nursery runoff.     

Responses of hybrid striped bass to waterborne and dietary copper in freshwater and saltwater

Mechanisms of copper toxicity and consequences of exposure vary due to uptake route and ionoregulatory status. The goal of this research was to develop a model fish system to assess the influence of different Cu exposure routes (waterborne or dietary) on bioavailability, uptake, and effects in hybrid striped bass (Morone chrysops x Morone saxatilis) acclimated to fresh- or saltwater. Initially, hybrid striped bass were exposed to dietary Cu concentrations of 571, 785, and 1013 mug Cu/g, along with a control (approximately 5 microg Cu/g), for 14 days in saltwater. Intestinal and liver Cu accumulated in a dose-dependent manner in fish exposed to increasing levels of dietary Cu. Chronic (42 days) experiments were then conducted to determine sub-lethal effects of aqueous, dietary, and combined aqueous and dietary Cu exposures to both freshwater- and saltwater-acclimated hybrid striped bass. Growth and Cu accumulation in the gill, intestine, and liver were measured. Although no significant effects were observed in fish exposed to waterborne Cu, those exposed through the diet accumulated significant liver and intestinal Cu but showed no significant change in growth. Overall, these results suggest that at the levels tested, exposure to elevated waterborne Cu did not cause significant long-term tissue Cu accumulation, whereas dietary Cu exposure caused significant liver and intestinal Cu accumulation in hybrid striped bass which was comparable in both freshwater and saltwater (15 g/L).     

Amiloride does not alter NaCl avoidance in Fischer-344 rats

Fischer-344 (F-344) rats differ from other common rat strains in that they fail to show any preference for NaCl at any concentration in two- bottle preference tests. Because 100 microM amiloride partially blocks the NaCl-evoked chorda tympani (CT) response in electrophysiological studies, we tested NaCl preference (0.068-0.273 M) in F-344 rats with and without 100 microM amiloride solution as the solvent. A third group was tested with unadulterated NaCl solutions following CT transection. Amiloride had no significant effect on the NaCl preference-aversion function, whereas CT transection significantly reduced NaCl avoidance. These results suggest that the amiloride-sensitive component of the NaCl response is not necessary for F-344 rats to display avoidance of NaCl, but the entire CT input is.      

Using the longest significance run to estimate region-specific p-values in genetic association mapping studies

Background  

Association testing is a powerful tool for identifying disease susceptibility genes underlying complex diseases. Technological advances have yielded a dramatic increase in the density of available genetic markers, necessitating an increase in the number of association tests required for the analysis of disease susceptibility genes. As such, multiple-tests corrections have become a critical issue. However the conventional statistical corrections on locus-specific multiple tests usually result in lower power as the number of markers increases. Alternatively, we propose here the application of the longest significant run (LSR) method to estimate a region-specific p-value to provide an index for the most likely candidate region.