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F Gould

Publications and source records attributed to F Gould.

35 records · Page 2Linked to original sources
PubMed1999

Overexpression of the Bacillus thuringiensis (Bt) Cry2Aa2 protein in chloroplasts confers resistance to plants against susceptible and Bt-resistant insects.

Evolving levels of resistance in insects to the bioinsecticide Bacillus thuringiensis (Bt) can be dramatically reduced through the genetic engineering of chloroplasts in plants. When transgenic tobacco leaves expressing Cry2Aa2 protoxin in chloroplasts were fed to susceptible, Cry1A-resistant (20,000- to 40,000-fold) and Cry2Aa2-resistant (330- to 393-fold) tobacco budworm Heliothis virescens, cotton bollworm Helicoverpa zea, and the beet armyworm Spodoptera exigua, 100% mortality was observed against all insect species and strains. Cry2Aa2 was chosen for this study because of its toxicity to many economically important insect pests, relatively low levels of cross-resistance against Cry1A-resistant insects, and its expression as a protoxin instead of a toxin because of its relatively small size (65 kDa). Southern blot analysis confirmed stable integration of cry2Aa2 into all of the chloroplast genomes (5, 000-10,000 copies per cell) of transgenic plants. Transformed tobacco leaves expressed Cry2Aa2 protoxin at levels between 2% and 3% of total soluble protein, 20- to 30-fold higher levels than current commercial nuclear transgenic plants. These results suggest that plants expressing high levels of a nonhomologous Bt protein should be able to overcome or at the very least, significantly delay, broad spectrum Bt-resistance development in the field.

Animals↗
PubMed1998

Supplemental social services improve outcomes in public addiction treatment.

AIMS: To evaluate the effectiveness and value of social services added to standard addiction rehabilitation. DESIGN: A controlled, quasi-experimental, field study with repeated measures. SETTING: Conducted in two groups of publicly supported outpatient addiction treatment programs. Control programs provided standard, twice-weekly, outpatient group counseling. "Enhanced" programs provided standard counseling but also case managers to coordinate and expedite use of pre-contracted medical screenings, housing assistance, parenting classes and employment services. MEASUREMENTS: The Addiction Severity Index was used to record the nature and severity of patient problems in seven areas at treatment admission and at 6-month follow-up. Services provided during treatment were measured with the Treatment Services Review. Measures were taken on consecutive samples of patients admitted to all programs--before enhancements (wave 1, N = 431)--and at 12 months (wave 2, N = 710); and 26 months following enhancements (wave 3, N = 187). FINDINGS: There were no significant differences in patient characteristics, treatment services or 6-month outcomes of the two sets of programs in wave 1. Wave 2 and especially wave 3 enhanced programs provided significantly more social and medical services than control programs. Patients treated in enhanced programs showed significantly less substance use, fewer physical and mental health problems and better social function at 6-months than Controls. CONCLUSIONS: Adding social services to public sector programs substantially improved the outcomes of addiction treatment. Changes in "real world" systems require time to implement; early evaluations may fail to capture the full impact of those changes.

Adult↗
PubMed1998

Manipulating natural enemies by plant variety selection and modification: a realistic strategy?

The host plants of arthropod pests may affect parasitoids and predators directly or indirectly, through multitrophic interactions. Direct plant effects may involve simple mechanisms such as reduced parasitoid searching efficiency caused by trichomes. Multitrophic effects often involve complex interactions that are not well understood, and their impact on natural enemies and biological control are difficult to predict. Knowledge of the direct and multitrophic effects creates opportunities to increase the effectiveness of natural enemies by incorporating natural enemy-enhancing traits into crop plants. The strategy may have potential for both generalist and specialist natural enemies, but the enemies' behavior and other factors will affect the results. Although combining natural enemies and plant resistance may slow the adaptation of some insect pests, it may speed up adaptations of others. A better understanding of plant/pest/natural enemy evolution is necessary to predict how to combine natural enemies and plant resistance for the best long-term results.

Journal Article↗
PubMed1998

Sustainability of transgenic insecticidal cultivars: integrating pest genetics and ecology.

This review examines potential impacts of transgenic cultivars on insect population dynamics and evolution. Experience with classically bred, insecticidal cultivars has demonstrated that a solid understanding of both the target insect's ecology and the cultivar's performance under varied field conditions will be essential for predicting area-wide effects of transgenic cultivars on pest and natural enemy dynamics. This experience has also demonstrated the evolutionary capacity of pests for adaptive response to insecticidal traits in crops. Biochemical and genetic studies of insect adaptation to the Bacillus thuringiensis (Bt) toxins expressed by currently marketed transgenic cultivars indicate a high risk for rapid adaptation if these cultivars are misused. Theoretical and practical issues involved in implementing strategies to delay pest adaptation to insecticidal cultivars are reviewed. Emphasis is placed on examining the "high dose"/refuge strategy that has become the goal of industry and regulatory authorities.

Journal Article↗
PubMed1998

Structure of the human D1F15S1A locus: a chromosome 1 locus with 97% identity to the chromosome 3 gene coding for hepatocyte growth factor-like protein.

The human chromosome 3 locus coding for hepatocyte growth factor-like protein/macrophage stimulating protein (HGFL/MSP) is homologous to two sets of amplified loci on human chromosome 1 at 1p36. One copy of one of the amplified loci (D1F15S1A) has been further characterized by restriction enzyme and DNA sequence analysis. A total of 8331 bp of continuous sequence was determined for this locus. The first 6878 bp of sequence is 96.1% identical to the HGFL/MSP gene, while there is no homology between the two genes following nucleotide 6878. Based on the presence of a 5 bp deletion in putative exon 2 and several downstream stop codons it is very likely that this gene is a pseudogene. Screening of a human liver cDNA library with a chromosome 1-specific probe indicates that at least several other members of the chromosome 1 loci are transcribed.

Chromosomes, Human, Pair 1↗
PubMed1997

Initial frequency of alleles for resistance to Bacillus thuringiensis toxins in field populations of Heliothis virescens.

The risk of rapid pest adaptation to an insecticide is highly dependent on the initial frequency of resistance alleles in field populations. Because we have lacked empirical estimates of these frequencies, population-genetic models of resistance evolution have relied on a wide range of theoretical estimates. The recent commercialization of genetically engineered cotton that constitutively produces an insecticidal protein derived from the biocontrol agent, Bacillus thuringiensis (Bt) has raised concern that we lack data needed to quantify the risk of insect pests such as Heliothis virescens rapidly adapting to this ecologically valuable class of toxins. By individually mating over 2,000 male H. virescens moths collected in four states to females of a Bt toxin-resistant laboratory strain, and screening F1 and F2 offspring for tolerance of the toxic protein, we were able to directly estimate the field frequency of alleles for resistance as 1.5 x 10(-3). This high initial frequency underscores the need for caution in deploying transgenic cotton to control insect pests. Our single-pair mating technique greatly increases the efficiency of detecting recessive resistance alleles. Because alleles that decrease target site sensitivity to Bt toxins and other insecticides are often recessive, this technique could be useful in estimating resistance allele frequencies in other insects exposed to transgenic insecticidal crops or conventional insecticides.

Journal Article↗
PubMed1997

Absorption of oligodeoxynucleotide by suppository from rat rectal route.

Rectal absorption of 32-mer phosphorothioate deoxynucleotides (S-Oligo) in the rat was attempted with the aid of a suppository containing oleic acid and a surfactant. Although, the suppository without adjuvant did not show detectable blood levels, that containing over 10% oleic acid enabled the absorption of S-Oligo with tmax at 2 h postdosing.

Administration, Rectal↗
PubMed1996

Mutations at domain II, loop 3, of Bacillus thuringiensis CryIAa and CryIAb delta-endotoxins suggest loop 3 is involved in initial binding to lepidopteran midguts.

Alanine substitutions of loop 3 residues, 438SGFSNS443, of CryIAb toxin were constructed to study the functional role of these residues in receptor binding and toxicity to Manduca sexta and Heliothis virescens. Experiments with trypsin and insect gut juice enzyme digestions of mutant toxins showed that these mutations did not produce any gross structural changes to the toxin molecule. Bioassay data showed that mutant G439A (alanine substitution of residue Gly439) and F440A significantly reduced toxicity toward M. sexta and H. virescens. In contrast, mutants S438A, S441A, N442A, and S443A were similar or only marginally less toxic (2-3 times) to the insects compared to the wild-type toxin. Binding studies with brush border membrane vesicles prepared from M. sexta and H. virescens midgut membranes revealed that the loss of toxicity of mutants G439A and F440A was attributable to substantially reduced initial binding. Consistent with the initial binding, mutants G349A and F440A showed 3.5 times less binding to M. sexta and H. virescens brush border membrane vesicles, although the off-rate of bound toxins was not affected. The role of hydrophobic residue, Phe440, is distinctly different from our previous observation that alanine substitution of Phe371 at loop 2 of CryIAb did not affect initial binding but reduced irreversible association of the toxin to the receptor or membrane toward M. sexta (Rajamohan, F., Alcantara, E., Lee, M. K., Chen, X. J., and Dean, D. H. (1995) J. Bacteriol. 177, 2276-2282). Likewise, deletion of relatively hydrophobic CryIAa loop 3 residues, 440AAGA443 (D3a), resulted in reduced toxicity to Bombyx mori (>62 times less) and M. sexta (28 times less). The loss of toxicity was correlated with reduced initial binding to midgut vesicles prepared from these insects. However, alanine substitution of residues 437LSQ439 (A3a), contiguous to loop 3, altered neither toxicity nor receptor binding toward B. mori or M. sexta. These results suggest that the loop 3 residues of CryIAb and CryIAa toxins establish hydrophobic interactions with the receptor molecule, and mutations at these hydrophobic residues affect initial binding.

Amino Acid Sequence↗
PubMed1996

Role of domain II, loop 2 residues of Bacillus thuringiensis CryIAb delta-endotoxin in reversible and irreversible binding to Manduca sexta and Heliothis virescens.

Site-directed mutagenesis was used to examine the role of domain II, loop 2 residues, 368RRPFNIGI375, of Bacillus thuringiensis insecticidal protein CryIAb. Alanine substitution of residues 368RRP370, called B4, abolished potency toward Manduca sexta and Heliothis virescens, and the loss of toxicity was correlated directly to substantially reduced binding affinity to brush-border membrane vesicles (BBMV) prepared from the target insect midguts. These results indicated that these positive charges might be essential to orient the toxin to midgut receptor molecule(s). The role of residue Phe371 of CryIAb toxin to M. sexta was investigated by substituting a series of residues at this position. Irreversible binding and toxicity were affected significantly by hydrophilic, aliphatic, and smaller side-chain residues such as Cys, Val, Leu, and Ser but not by Tyr or Trp. A hydrophobic aromatic side-chain residue at position 371 was therefore essential for irreversible binding of CryIAb toxin in M. sexta. The role of residues 370PFNIGI375 of CryIAb toxin on H. virescens was also examined. Mutants D2 (deletion of residues 370-375), G374A (alanine substitution of Gly374), and I375A had reduced toxicity to H. virescens. In contrast to our findings with M. sexta, the reduction in toxicity of these mutants was correlated directly with loss of initial binding to H. virescens BBMV, indicating that these residues perform functionally distinct roles in binding and toxicity to different insects. In ligand blots, CryIAb recognized a major 210-kDa peptide in M. sexta BBMV and a 170-kDa peptide in H. virescens BBMV.

Amino Acid Sequence↗
PubMed1995

Resistance to Bacillus thuringiensis CryIA delta-endotoxins in a laboratory-selected Heliothis virescens strain is related to receptor alteration.

The Bacillus thuringiensis toxin-binding properties of midgut epithelial cells from two strains of Heliothis virescens were compared. One H. virescens strains (YHD2) which was selected against CryIAc toxin had over 10,000-fold resistance to CryIAc toxin relative to the susceptible strain and was cross-resistant to CryIAa and CryIAb. The second H. virescens strain (YDK) was susceptible to these toxins in the order CryIAc > CryIAb > CryIAa. Receptor-binding properties of CryIAa, CryIAb, and CryIAc toxins were compared between the susceptible and resistant strains. Saturation and competition-binding experiments were performed with brush border membrane vesicles prepared from midguts of the susceptible and resistant insects and 125I-labeled toxins. In the susceptible strain, saturable, specific, and high-affinity binding of all three toxins was observed. The relative binding-site concentration was directly correlated with toxicity (CryIAc > CryIAb > CryIAa). In the resistant strains, the binding affinities of CryIAb and CryIAc were similar to that observed with the susceptible strain and ony minor differences in binding-site concentration (Bmax) were observed. The major difference between the two strains was the total lack of binding of CryIAa toxin to the brush border membrane vesicles of the resistant strain. Heterologous competition-binding experiments and ligand blot analysis supported the hypothesis that there were multiple binding sites for the toxins. On the basis of results of the present study, we propose that alterations in binding proteins shared by all three toxins are a major factor in resistance. This suggests that not all receptors of CryIAc might be involved in toxic function.

Animals↗
PubMed1992

Broad-spectrum resistance to Bacillus thuringiensis toxins in Heliothis virescens.

Evolution of pest resistance to insecticidal proteins produced by Bacillus thuringiensis (Bt) would decrease our ability to control agricultural pests with genetically engineered crops designed to express genes coding for these proteins. Previous genetic and biochemical analyses of insect strains with resistance to Bt toxins indicate that (i) resistance is restricted to single groups of related Bt toxins, (ii) decreased toxin sensitivity is associated with changes in Bt-toxin binding to sites in brush-border membrane vesicles of the larval midgut, and (iii) resistance is inherited as a partially or fully recessive trait. If these three characteristics were common to all resistant insects, specific crop-variety deployment strategies could significantly diminish problems associated with resistance in field populations of pests. We present data on Bt-toxin resistance in Heliothis virescens, a major agricultural pest targeted for control with Bt-toxin-producing crops. A laboratory strain of H. virescens developed resistance in response to selection with the Bt toxin CryIA(c). In contrast to other cases of Bt-toxin resistance, this H. virescens strain exhibits cross-resistance to Bt toxins that differ significantly in structure and activity. Furthermore, the resistance in this strain is not accompanied by significant changes in toxin binding, and resistance is inherited as an additive trait when larvae are treated with high doses of CryIA(c) toxin. These findings have important implications for Bt-toxin-based pest control.

Journal Article↗
PubMed1980

Public spending and social policy: the United Kingdom 1950-1977.

This article, in which we examine developments in public expenditure on social policy in relation to total public spending in the United Kingdom (UK) in the period after the Second World War, is part of a larger international study on developments in social welfare spending on which we are currently engaged. In Section 1 we briefly sketch in the theoretical background to the study of public expenditure growth in general and social welfare spending iompeting hypotheses - this exercise is in hand as part of the international study, and we shall report the finding at a later date. Section 2 examines the growth of public expenditure in the UK at the aggregate level. In Section 3 we analyse public expenditure at the individual programme level and in Section 4 we summarize the conclusions.

Costs and Cost Analysis↗
PubMed1976

Comparison of rapid versus slow decompression of the distended urinary bladder.

Experiments are described showing that urinary retention with its associated increased intravesical pressure and overstretching of the bladder wall can lead to loss of capillary and tissue integrity. Our findings indicate that the severity of damage to the bladder wall prior to catheterization determines the degree of hemorrhage after bladder decompression and not the rate of emptying.

Animals↗