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TV presenter turned cancer campaigner Lynn Faulds Wood launches a new campaign to mark Bowel Cancer Awareness month in April. Here she outlines how nurses can help. [ABSTRACT FROM AUTHOR]

Competing Interests: Competing interest statement: We have read and understood BMJ policy on declaration of interests and declare that we have no competing interests.

BCG vaccination has been demonstrated to increase levels of activated CD4+ T cells, thus potentially influencing mother-to-child transmission of human immunodeficiency virus (HIV). To assess the risk of BCG vaccination in HIV infection, we randomly assigned newborn rhesus macaques to receive BCG vaccine or remain unvaccinated and then undergo oral simian immunodeficiency virus (SIV) challenges 3 weeks later. We observed elevated levels of activated peripheral CD4+ T cells (ie, HLA-DR+CD38+CCR5+ CD4+ T cells) by week 3 after vaccination. BCG was also associated with an altered immune gene expression profile, as well as with monocyte activation in both peripheral blood and the draining axillary lymph node, indicating significant BCG vaccine-induced immune activation. Despite these effects, BCG vaccination did not increase the rate of SIV oral transmission or disease progression. Our findings therefore identify patterns of T-cell and monocyte activation that occur after BCG vaccination but do not support the hypothesis that BCG vaccination is a risk factor for postnatal HIV transmission or increased pathogenesis in infants., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Congenital anomalies of the female reproductive tract are relatively common and can be both confusing to understand as well as challenging to diagnose and manage in a busy pediatric clinical practice. Here, we lay out some of the most common genitourinary tract anomalies in female pediatric patients. We highlight the key embryologic development, present case examples, and discuss appropriate testing, treatment, and counseling for patients and their families regarding congenital disorders of the vulva, vagina, uterus, ovaries, and associated pathology. The goal of this review is to demystify these conditions and provide a practical guide for the general pediatrician who is often at the frontline making the initial diagnosis and caring for these patients. [Pediatr Ann. 2020;49(4):e188-e195.]., (Copyright 2020, SLACK Incorporated.)

Background: Exclusive breastfeeding reduces the rate of postnatal human immunodeficiency virus (HIV) transmission compared to nonexclusive breastfeeding; however, the mechanisms of this protection are unknown. Our study aimed to interrogate the mechanisms underlying the protective effect of exclusive breastfeeding., Methods: We performed a prospective, longitudinal study of infants from a high-HIV-prevalence, low-income setting in South Africa. We evaluated the role of any non-breast milk feeds, excluding prescribed medicines on stool microbial communities via 16S rRNA gene sequencing, peripheral T-cell activation via flow cytometry, and buccal mucosal gene expression via quantitative polymerase chain reaction assay., Results: A total of 155 infants were recruited at birth with mean gestational age of 38.9 weeks and mean birth weight of 3.2 kg. All infants were exclusively breastfed (EBF) at birth, but only 43.5% and 20% remained EBF at 6 or 14 weeks of age, respectively. We observed lower stool microbial diversity and distinct microbial composition in exclusively breastfed infants. These microbial communities, and the relative abundance of key taxa, were correlated with peripheral CD4+ T-cell activation, which was lower in EBF infants. In the oral mucosa, gene expression of chemokine and chemokine receptors involved in recruitment of HIV target cells to tissues, as well as epithelial cytoskeletal proteins, was lower in EBF infants., Conclusions: These data suggest that nonexclusive breastfeeding alters the gut microbiota, increasing T-cell activation and, potentially, mucosal recruitment of HIV target cells. Study findings highlight a biologically plausible mechanistic explanation for the reduced postnatal HIV transmission observed in EBF infants.

This article provides Section 1 of the 2017 Edition 2 Medical Writing Competency Model that describes the core work functions and associated tasks and activities related to professional medical writing within the life sciences industry. The functions in the Model are scientific communication strategy; document preparation, development, and finalization; document project management; document template, standard, format, and style development and maintenance; outsourcing, alliance partner, and client management; knowledge, skill, ability, and behavior development and sharing; and process improvement. The full Model also includes Section 2, which covers the knowledge, skills, abilities, and behaviors needed for medical writers to be effective in their roles; Section 2 is presented in a companion article. Regulatory, publication, and other scientific writing as well as management of writing activities are covered. The Model was developed to aid medical writers and managers within the life sciences industry regarding medical writing hiring, training, expectation and goal setting, performance evaluation, career development, retention, and role value sharing to cross-functional partners.

This article provides Section 2 of the 2017 Edition 2 Medical Writing Competency Model that describes the knowledge, skills, abilities, and behaviors that professional medical writers need in order to perform effectively within the life sciences industry. What a medical writer should know, what they should be able to do, and how they should use this knowledge and these skills to facilitate their primary work function is a focus. Regulatory, publication, and other scientific writing as well as management of writing activities are covered. The full Model also includes Section 1, which covers the core work functions and associated tasks and activities related to professional medical writing within the life sciences industry; Section 1 is included in a companion article. The Model was developed to aid medical writers and managers within the life sciences industry regarding medical writing hiring, training, expectation and goal setting, performance evaluation, career development, retention, and role value sharing to cross-functional partners.

The introduction of non-breastmilk foods to HIV-infected infants is associated with increased levels of immune activation, which can impact the rate of HIV disease progression. This is particularly relevant in countries where mother-to-child transmission of HIV still occurs at unacceptable levels. The goal of this study was to evaluate the levels of the toxic food contaminant ochratoxin A (OTA) in HIV-exposed South African infants that are either breastfed or consuming non-breast milk foods. OTA is a common mycotoxin, found in grains and soil, which is toxic at high doses but has immunomodulatory properties at lower doses. Samples from HIV-exposed and HIV-unexposed infants enrolled in prospective observational cohort studies were collected and analyzed at birth through 14 weeks of age. We observed that infants consuming non-breast milk foods had significantly higher plasma levels of OTA at 6 weeks of age compared to breastfed infants, increasing until 8 weeks of age. The blood levels of OTA detected were comparable to levels observed in OTA-endemic communities. OTA plasma levels correlated with HIV target cell activation (CCR5 and HLADR expression on CD4+ T cells) and plasma levels of the inflammatory cytokine CXCL10. These findings provide evidence that elevated OTA levels in South African infants are associated with the consumption of non-breastmilk foods and activation of the immune system. Reducing infant OTA exposure has the potential to reduce immune activation and provide health benefits, particularly in those infants who are HIV-exposed or HIV-infected.

The ECF (extracytoplasmic function) alternative sigma factor, σ(22) (AlgT/U), is required for expression of the algD promoter of the operon for alginate biosynthesis in Pseudomonas aeruginosa. Alginate production promotes chronic pulmonary infections by this opportunistic pathogen in patients with cystic fibrosis and chronic obstructive pulmonary disease. σ(22) is normally sequestered, but its deregulation and activation occur either by mutation in mucA (encoding an anti-sigma factor) or in response to envelope stress, such as inhibition of peptidoglycan synthesis. The σ(22) stress response system includes many genes in addition to those for alginate. In the present study, we characterized an intergenic region between ORFs PA2559 and PA2560 in PAO1 for a σ(22)-dependent, stress-responsive transcript, described here as PA2559.1. Northern analysis and transcript end-mapping indicated the PA2559.1 transcript was ~310 nt in length. Examination of the DNA sequence upstream of +1 revealed a σ(22) core promoter motif, GAATTT-N16-TCTGT, and site-directed mutagenesis confirmed this to be a σ(22)-dependent promoter that was highly activated during cell wall stress. PA2559.1 also contained an ORF that demonstrated increased translational activity upon cell wall stress. As determined by mutant analysis, the protein encoded by PA2559.1 was shown to play a positive role in the σ(22)-dependent activation of the algD promoter under stress in both sessile (i.e. biofilm) and planktonic conditions. Thus, it appeared to act as a stress response facilitator and so was named SrfA. The sequence of SrfA was found to be novel in nature and extremely well conserved only in P. aeruginosa, suggesting that it is of high evolutionary importance in this species., (© 2015 The Authors.)

The alkyl chain length of quaternary ammonium/PEG copolyoxetanes has been varied to discern effects on solution antimicrobial efficacy, hemolytic activity and cytotoxicity. Monomers 3-((4-bromobutoxy)methyl)-3-methyloxetane (BBOx) and 3-((2-(2-methoxyethoxy)ethoxy)methyl)-3-methyloxetane (ME2Ox) were used to prepare precursor P[(BBOx)(ME2Ox)-50:50-4 kDa] copolyoxetane via cationic ring opening polymerization. The 1:1 copolymer composition and Mn (4 kDa) were confirmed by (1)H NMR spectroscopy. After C-Br substitution by a series of tertiary amines, ionic liquid Cx-50 copolyoxetanes were obtained, where 50 is the mole percent of quaternary repeat units and "x" is quaternary alkyl chain length (2, 6, 8, 10, 12, 14, or 16 carbons). Modulated differential scanning calorimetry (MDSC) studies showed Tgs between -40 and -60 °C and melting endotherms for C14-50 and C16-50. Minimum inhibitory concentrations (MIC) were determined for Escherichia coli , Staphylococcus aureus , and Pseudomonas aeruginosa . A systematic dependence of MIC on alkyl chain length was found. The most effective antimicrobials were in the C6-50 to C12-50 range. C8-50 had better overall performance with MICs of 4 μg/mL, E. coli ; 2 μg/mL, S. aureus ; and 24 μg/mL, P. aeruginosa . At 5 × MIC, C8-50 effected >99% kill in 1 h against S. aureus , E. coli , and P. aeruginosa challenges of 10(8) cfu/mL; log reductions (1 h) were 7, 3, and 5, respectively. To provide additional insight into polycation interactions with bacterial membranes, a geometric model based on the dimensions of E. coli is described that provides an estimate of the maximum number of polycations that can chemisorb. Chain dimensions were estimated for polycation C8-50 with a molecular weight of 5 kDa. Considering the approximations for polycation chemisorption (PCC), it is surprising that a calculation based on geometric considerations gives a C8-50 concentration within a factor of 2 of the MIC, 4.0 (±1.2) μg/mL for E. coli . Cx-50 copolyoxetane cytotoxicity was low for human red blood cells, human dermal fibroblasts (HDF), and human foreskin fibroblasts (HFF). Selectivities for bacterial kill over cell lysis were among the highest ever reported for polycations indicating good prospects for biocompatibility.

The global spread of human immunodeficiency virus (HIV) is dependent on the ability of this virus to efficiently cross from one host to the next by traversing a mucosal membrane. Unraveling how mucosal exposure of HIV results in systemic infection is critical for the development of effective therapeutic strategies. This review focuses on understanding the immune events associated with the oral route of transmission (via breastfeeding or sexual oral intercourse), which occurs across the oral and/or gastrointestinal mucosa. Studies in both humans and simian immunodeficiency virus (SIV) monkey models have identified viral changes and immune events associated with oral HIV/SIV exposure. This review covers our current knowledge of HIV oral transmission in both infants and adults, the use of SIV models in understanding early immune events, oral immune factors that modulate HIV/SIV susceptibility (including mucosal inflammation), and interventions that may impact oral HIV transmission rates. Understanding the factors that influence oral HIV transmission will provide the foundation for developing immune therapeutic and vaccine strategies that can protect both infants and adults from oral HIV transmission., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Unlabelled: The Pseudomonas aeruginosa extracytoplasmic functioning (ECF) sigma factor σ(22) is encoded by algT/algU and is inhibited by anti-sigma factor MucA. σ(22) was originally discovered for its essential role in the expression of the exopolysaccharide alginate by mucoid strains associated with chronic pulmonary infection. However, σ(22) is now known to also have a large regulon associated with the response to cell wall stress. Our recent transcriptome analysis identified 293 open reading frames (ORFs) in the σ(22) stress stimulon that include genes for outer envelope biogenesis and remodeling, although most of the genes have undefined functions. To better understand the σ(22)-dependent stress response, mutants affected in 27 genes of the σ(22) stimulon were examined and expression was studied with lacZ fusions. Mutants constructed in the 27 genes showed no major change in response to cell wall-acting antibiotics or growth at elevated temperatures nor in alginate production. The mutants were examined for their effects on the expression of the σ(22)-dependent promoter of the alginate biosynthetic operon (PalgD) as a measure of σ(22) derepression from MucA. By testing PalgD expression under both planktonic and sessile growth conditions, 11 genes were found to play a role in the stress response that activates σ(22). Some mutations caused an increase or a decrease in the response to cell wall stress. Interestingly, mutations in 7 of the 11 genes caused constitutive PalgD expression under nonstressed conditions and thus showed that these genes are involved in maintaining envelope homeostasis. Mutations in PA0062 and PA1324 showed constitutive PalgD expression during both the planktonic and the sessile modes of growth. However, the PA5178 mutation caused constitutive PalgD expression only during planktonic growth. In contrast, mutations in PA2717, PA0567, PA3040, and PA0920 caused constitutive PalgD expression only in the sessile/biofilm mode of growth. This provides evidence that the σ(22) stimulon for cell envelope homeostasis overlaps with biofilm control mechanisms., Importance: During chronic lung infections, such as in cystic fibrosis patients, Pseudomonas aeruginosa produces the exopolysaccharide alginate and forms biofilms that shield the organisms from the immune response and increase resistance to antibiotics. Activation of alginate genes is under the control of an extracytoplasmic stress response system that releases an alternative sigma factor (σ(22)) in response to cell wall stress and then activates expression of a large regulon. In this study, a mutant analysis of 27 members of the regulon showed that 11 play a role in envelope homeostasis and affect the stress response system itself. Interestingly, some genes demonstrate effects only in either the planktonic (free-swimming) or the sessile (biofilm) mode of growth, which leads to persistence and antibiotic tolerance. The studies presented here provide an important initial step in dissecting the mechanisms that regulate a critical signal transduction pathway that impacts P. aeruginosa pathogenesis.

Pseudomonas aeruginosa is the predominant pathogen associated with chronic lung infection among cystic fibrosis patients. During colonization of the lung, P. aeruginosa converts to a mucoid phenotype characterized by the overproduction of the exopolysaccharide alginate. Secretion of newly synthesized alginate across the outer membrane is believed to occur through the outer membrane protein AlgE. Here we report the 2.3 Å crystal structure of AlgE, which reveals a monomeric 18-stranded β-barrel characterized by a highly electropositive pore constriction formed by an arginine-rich conduit that likely acts as a selectivity filter for the negatively charged alginate polymer. Interestingly, the pore constriction is occluded on either side by extracellular loop L2 and an unusually long periplasmic loop, T8. In halide efflux assays, deletion of loop T8 (ΔT8-AlgE) resulted in a threefold increase in anion flux compared to the wild-type or ΔL2-AlgE supporting the idea that AlgE forms a transport pathway through the membrane and suggesting that transport is regulated by T8. This model is further supported by in vivo experiments showing that complementation of an algE deletion mutant with ΔT8-AlgE impairs alginate production. Taken together, these studies support a mechanism for exopolysaccharide export across the outer membrane that is distinct from the Wza-mediated translocation observed in canonical capsular polysaccharide export systems.

This study focuses on the solution antimicrobial effectiveness of a novel class of copolyoxetanes with quaternary ammonium and PEG-like side chains. A precursor P[(BBOx-m)(ME2Ox)] copolyoxetane was prepared by cationic ring-opening copolymerization of 3-((4-bromobutoxy)methyl)-3-methyloxetane (BBOx) and 3-((2-(2-methoxyethoxy)ethoxy)methyl)-3-methyloxetane (ME2Ox) to give random copolymers with 14-100 (m) mol % BBOx. Reaction of P[(BBOx-m)(ME2Ox)] with dodecyl dimethylamine gave the corresponding quaternary P[(C12-m)(ME2Ox)] polycation salts, designated C12-m, as viscous liquids in 100% yield. BBOx/ME2Ox and C12/ME2Ox ratios were obtained by (1)H NMR spectroscopy. C12-m molecular weights (M(n), 3.5-21.9 kDa) were obtained from (1)H NMR end group analysis. DSC studies up to 150 °C showed only thermal transitions between -69 and -34 °C assigned to T(g) values. Antibacterial activity for the C12-m copolyoxetanes was tested by determining minimum inhibitory concentrations (MICs) against Gram(+) Staphylococcus aureus and Gram(-) Escherichia coli and Pseudomonas aeruginosa . MIC decreased with increasing C12 mol percent, reaching a minimum in the range C12-43 to C12-60. Overall, the antimicrobial with consistently low MICs for the three tested pathogenic bacteria was C12-43: (bacteria, MIC, μg/mL) E. coli (6), S. aureus (5), and P. aeruginosa (33). For C12-43, minimum biocidal concentration (MBC) to reach 99.99% kill in 24 h required 1.5× MIC for S. aureus and 2× MIC for E. coli and P. aeruginosa . At 5× MIC against a challenge of 10(8) cfu/mL, C12-43 kills ≥99% S. aureus , E. coli , and P. aeruginosa within 1 h. C12-m copolyoxetane cytotoxicity toward human red blood cells was low, indicating good prospects for biocompatibility. The tunability of C12-m copolyoxetane compositions, effective antimicrobial behavior against Gram(+) and Gram(-) bacteria, and promising biocompatibility offer opportunities for further modification and potential applications as therapeutic agents.

Aim: To determine current delays in diagnosis and treatment of bowel cancer, when and why they occur, and what effect they have on survival., Method: A detailed review of the literature based on the development of the GP referral guidelines in 2000., Results: There is no evidence of a reduction in the delay to diagnosis and treatment of bowel cancer over the last 60 years. There is no strong theoretical basis for a benefit from earlier diagnosis of symptomatic bowel cancer and this is consistent with observational studies., Conclusion: Campaigns to earlier diagnose bowel cancer will not be successful unless new strategies are developed. There is substantial evidence that earlier diagnosis of symptomatic bowel cancer will not improve survival in the majority of patients. However as excessive delays still occur in some patients it is reasonable to continue to aim to diagnose and treat all bowel cancer within 6 months of the onset of symptoms with an overall median of 3-4 months., (© 2010 The Authors. Colorectal Disease © 2010 The Association of Coloproctology of Great Britain and Ireland.)

Background: The government's proposals to openly report clinical outcomes poses challenges to the National Bowel Cancer Audit now funded by the UK department of health., Aim: To identify the benefits and risks of open reporting and to propose ways the risks might be minimized., Methods: A review of the literature on clinical audit and the consequences of open reporting., Results: There are significant potential benefits of a national audit of bowel cancer including protecting patients from sub-standard care, providing clinicians with externally validated evidence of their performance, outcome data for clinical governance and evidence that increases in government expenditure are achieving improvements in survival from bowel cancer. These benefits will only be achieved if the audit captures most of the cases of bowel cancer in the UK, the data collected is complete and accurate, the results are risk adjusted and these are presented to the public in a way that is fair, clear and understandable. Involvement of clinicians who have confidence in the results of the audit and who actively compare their own results against a national standard is essential. It is suggested that a staged move to open reporting should minimise the risk of falsely identifying an outlying unit., Conclusion: The fundamental aim of the National Bowel Cancer Audit is the pursuit of excellence by identification and adoption of best practice. This could achieve a continuous improvement in the care of all patients with bowel cancer in the UK. The ACPGBI suggests a safer way of transition to open reporting to avoid at least some of its pitfalls.

Bioinspired masks, created by merging sol-gel chemistry with biotemplating, were used as local chemical reactors to grow aligned arrays of gold nanoparticle-like wires.

MucA sequesters extracytoplasmic function (ECF) sigma(22) (algT/U encoded) from target promoters including PalgD for alginate biosynthesis. We have shown that cell wall stress (e.g. d-cycloserine) is a potent inducer of the algD operon. Here we showed that MucB, encoded by the algT-mucABCD operon, interacts with MucA in the sigma-sequestration complex. We hypothesized that AlgW protease (a DegS homologue) is activated by cell wall stress to cleave MucA and release sigma(22). When strain PAO1 was exposed to d-cycloserine, MucA was degraded within just 10 min, and sigma(22) was activated. However, in an algW mutant, MucA was stable with no increased sigma(22) activity. Studies on a yaeL mutant, defective in an RseP/YaeL homologue, suggest that YaeL protease cleaves MucA only after cleavage by AlgW. A defect in mucD, encoding a periplasmic HtrA/DegP homologue, caused MucA instability, suggesting MucD degrades cell wall stress signals. Overall, these data indicate that cell wall stress signals release sigma(22) by regulated intramembrane proteolysis (RIP). Microarray analyses identified genes of the early and late cell wall stress stimulon, which included genes for alginate production. The subset of genes in the sigma(22) regulon was then determined, which included gene products predicted to contribute to recovery from cell wall stress.

A bioassay was developed to identify stimuli that promote the transcriptional induction of the algD operon for alginate biosynthesis in Pseudomonas aeruginosa. Strain PAO1 carried the algD promoter fused to a chloramphenicol acetyl-transferase cartridge (PalgD-cat), and > 50 compounds were tested for promoting chloramphenicol resistance. Most compounds showing PalgD-cat induction were cell wall-active antibiotics that blocked peptidoglycan synthesis. PalgD-cat induction was blocked by mutations in the genes for sigma22 (algT/algU) or regulators AlgB and AlgR. Anti-sigma factor MucA was the primary regulator of sigma22 activity. A transcriptome analysis using microarrays verified that the algD operon undergoes high induction by D-cycloserine. A similar sigma(E)-RseAB complex in Escherichia coli responds to envelope stress, which requires DegS protease in a regulated intramembrane proteolysis (RIP) cascade to derepress the sigma. Mutant phenotypic studies in P. aeruginosa showed that AlgW (PA4446) is likely to be the DegS functional homologue. A mutation in algW resulted in a complete lack of PalgD-cat induction by D-cycloserine. Overexpression of algW in PAO1 resulted in a mucoid phenotype and alginate production, even in the absence of cell wall stress, suggesting that AlgW protease plays a role in sigma22 activation. In addition, a mutation in gene PA3257 (prc), encoding a Prc-like protease, resulted in poor induction of PalgD-cat by D-cycloserine, suggesting that it also plays a role in the response to cell wall stress.

Expression of mucD, encoding a homologue of the HtrA(DegP) family of endoserine proteases, was investigated in Pseudomonas aeruginosa. Expressed from the algT-mucABCD operon, MucD was detected in mucoid (FRD1) and nonmucoid (PAO1) parental strains and also when polar insertions were placed upstream in algT or mucB. A transcriptional start site for a mucD promoter (PmucD) was mapped within mucC. Expression of single-copy mucD217, encoding MucD altered in the protease motif (S217A), was defective in temperature resistance and alginate gene regulation.

A comprehensive two-dimensional (2D) retention time alignment algorithm was developed using a novel indexing scheme. The algorithm is termed comprehensive because it functions to correct the entire chromatogram in both dimensions and it preserves the separation information in both dimensions. Although the algorithm is demonstrated by correcting comprehensive two-dimensional gas chromatography (GC x GC) data, the algorithm is designed to correct shifting in all forms of 2D separations, such as LC x LC, LC x CE, CE x CE, and LC x GC. This 2D alignment algorithm was applied to three different data sets composed of replicate GC x GC separations of (1) three 22-component control mixtures, (2) three gasoline samples, and (3) three diesel samples. The three data sets were collected using slightly different temperature or pressure programs to engender significant retention time shifting in the raw data and then demonstrate subsequent corrections of that shifting upon comprehensive 2D alignment of the data sets. Thirty 12-min GC x GC separations from three 22-component control mixtures were used to evaluate the 2D alignment performance (10 runs/mixture). The average standard deviation of first column retention time improved 5-fold from 0.020 min (before alignment) to 0.004 min (after alignment). Concurrently, the average standard deviation of second column retention time improved 4-fold from 3.5 ms (before alignment) to 0.8 ms (after alignment). Alignment of the 30 control mixture chromatograms took 20 min. The quantitative integrity of the GC x GC data following 2D alignment was also investigated. The mean integrated signal was determined for all components in the three 22-component mixtures for all 30 replicates. The average percent difference in the integrated signal for each component before and after alignment was 2.6%. Singular value decomposition (SVD) was applied to the 22-component control mixture data before and after alignment to show the restoration of trilinearity to the data, since trilinearity benefits chemometric analysis. By applying comprehensive 2D retention time alignment to all three data sets (control mixtures, gasoline samples, and diesel samples), classification by principal component analysis (PCA) substantially improved, resulting in 100% accurate scores clustering.

Bacteriophage P2 late transcription requires the product of the P2 ogr gene. Ogr-dependent transcription from P2 late promoters is blocked by certain point mutations affecting the alpha subunits of the host RNA polymerase. An alanine scan spanning the putative activation target in the alpha C-terminal domain (alphaCTD) was carried out to identify individual residues essential for Ogr-dependent transcription from P2 late promoters. In addition, the effects of alanine substitutions in the regions of the alphaCTD previously reported to affect CAP-dependent activation of the lac promoter and UP-element DNA binding were examined. Residues E286, V287, L289 and L290 in helix 3, and residue L300 at the beginning of helix 4, define a surface-exposed patch on the alphaCTD important for Ogr-dependent activation. These residues, adjacent to the recently identified DNA-binding determinants, constitute a newly identified activation surface for protein:protein contact. Alanine substitutions at some of the residues that affect UP-element DNA binding also impaired activation. This suggests that upstream DNA-alpha contacts, in addition to alpha-Ogr contacts, may be important in P2 late transcription. Other residues implicated in the interaction of alpha with CAP are not required for activation by Ogr, consistent with previous genetic evidence suggesting that these activators contact different sites on the alphaCTD., (Copyright 1997 Academic Press Limited.)

The purpose of this study was to compare our structured research-based version of marital therapy from a social learning perspective with a clinically flexible version of the same treatment where treatment plans were individually-based and there was no specific number of treatment sessions. Thirty distressed married couples were randomly assigned to one of these two treatments. Assessment of outcome was based on global marital satisfaction, spouse reports of functioning in specific areas, and direct observational measures of communication. At posttest there were no differences in efficacy between structured and flexible treatments, although both treatments led to significant improvements. At a 6-month follow-up couples treated with the structured format were more likely to have deteriorated and flexibly treated couples were more likely to have maintained their treatment gains.