Subunit assembly modulates the activities of the Type III restriction–modification enzyme PstII in vitro

We demonstrate that, like other Type III restriction endonuclease, PstII does not turnover such that a DNA substrate is only fully cleaved at a Res(2)Mod(2)-to-site ratio of ∼1:1. However, unlike other Type III enzymes, the cleavage rate profiles varied with protein concentration: using 5 nM DNA and 25 nM PstII, approximately half of the DNA was cut at a fast rate while the remainder was cut 24 times more slowly; in comparison, with 100 nM PstII cleavage occurs at a single fast rate. The inclusion of the methyl donor S-adenosyl methionine does not alter the rates with 100 nM PstII but with 25 nM PstII the reaction stopped after completion of the initial fast cleavage phase owing to methylation. Concentration-dependent rates were also observed in methylation assays: at 100 nM PstII, a single slow rate was measured while at lower PstII concentrations both fast and slow rates were measured. We propose a model in which the intact Res(2)Mod(2) complex favoured at high PstII concentrations is a fast endonuclease/slow methyltransferase while the various subassemblies which coexist at lower concentrations are fast methyltransferases. A potential role for disassembly in control of restriction activity in vivo is discussed

Verbal task demands are key in explaining the relationship between paired-associate learning and reading ability

Paired-associate learning (PAL) tasks measure the ability to form a novel association between a stimulus and a response. Performance on such tasks is strongly associated with reading ability, and there is increasing evidence that verbal task demands may be critical in explaining this relationship. The current study investigated the relationships between different forms of PAL and reading ability. A total of 97 children aged 8–10 years completed a battery of reading assessments and six different PAL tasks (phoneme–phoneme, visual–phoneme, nonverbal–nonverbal, visual–nonverbal, nonword–nonword, and visual–nonword) involving both familiar phonemes and unfamiliar nonwords. A latent variable path model showed that PAL ability is captured by two correlated latent variables: auditory–articulatory and visual–articulatory. The auditory–articulatory latent variable was the stronger predictor of reading ability, providing support for a verbal account of the PAL–reading relationship

Verbal task demands are key in explaining the relationship between paired-associate learning and reading ability

Paired-associate learning (PAL) tasks measure the ability to form a novel association between a stimulus and a response. Performance on such tasks is strongly associated with reading ability, and there is increasing evidence that verbal task demands may be critical in explaining this relationship. The current study investigated the relationships between different forms of PAL and reading ability. A total of 97 children aged 8–10 years completed a battery of reading assessments and six different PAL tasks (phoneme–phoneme, visual–phoneme, nonverbal–nonverbal, visual–nonverbal, nonword–nonword, and visual–nonword) involving both familiar phonemes and unfamiliar nonwords. A latent variable path model showed that PAL ability is captured by two correlated latent variables: auditory–articulatory and visual–articulatory. The auditory–articulatory latent variable was the stronger predictor of reading ability, providing support for a verbal account of the PAL–reading relationship

Childhood asthma and indoor allergens in Native Americans in New York

BACKGROUND: The objective of this study was to assess the correlation between childhood asthma and potential risk factors, especially exposure to indoor allergens, in a Native American population. METHODS: A case-control study of St. Regis Mohawk tribe children ages 2–14 years, 25 diagnosed with asthma and 25 controls was conducted. Exposure was assessed based on a personal interview and measurement of mite and cat allergens (Der p 1, Fel d 1) in indoor dust. RESULTS: A non-significant increased risk of childhood asthma was associated with self-reported family history of asthma, childhood environmental tobacco smoke exposure, and air pollution. There was a significant protective effect of breastfeeding against current asthma in children less than 14 years (5.2 fold lower risk). About 80% of dust mite and 15% of cat allergen samples were above the threshold values for sensitization of 2 and 1 μg/g, respectively. The association between current asthma and exposure to dust mite and cat allergens was positive but not statistically significant. CONCLUSION: This research identified several potential indoor and outdoor risk factors for asthma in Mohawks homes, of which avoidance may reduce or delay the development of asthma in susceptible individuals

Psychology and aggression

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68264/2/10.1177_002200275900300301.pd

Mothers construct fathers: Destabilized patriarchy in La Leche League

This paper examines changing masculine ideals from the point of view of women homemakers through a case study of La Leche League, a maternalist organization dedicated to breastfeeding and mother primacy. We suggest two reasons for studying the League: first, an emerging literature suggests that changing norms are seeping into many such seemingly conservative groups, and second, the League continues to be highly successful among white, middle-class, married women. The paper looks at two aspects of masculinity, examining changes in the League through fieldwork, interviews, and content analysis, and finds that new norms of increased father involvement and decreased rights over women's bodies have both influenced League philosophy. We conclude that while in some respects a measure of the decline of men's patriarchal privileges, the League's changes also may contribute to a “restabilization” of male dominance in a modified, partial form.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43548/1/11133_2004_Article_BF00990071.pd

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society