Mutational analysis of BTAF1-TBP interaction: BTAF1 can rescue DNA-binding defective TBP mutants

The BTAF1 transcription factor interacts with TATA-binding protein (TBP) to form the B-TFIID complex, which is involved in RNA polymerase II transcription. Here, we present an extensive mapping study of TBP residues involved in BTAF1 interaction. This shows that residues in the concave, DNA-binding surface of TBP are important for BTAF1 binding. In addition, BTAF1 interacts with residues in helix 2 on the convex side of TBP as assayed in protein-protein and in DNA-binding assays. BTAF1 drastically changes the TATA-box binding specificity of TBP, as it is able to recruit DNA-binding defective TBP mutants to both TATA-containing and TATA-less DNA. Interestingly, other helix 2 interacting factors, such as TFIIA and NC2, can also stabilize mutant TBP binding to DNA. In contrast, TFIIB which interacts with a distinct surface of TBP does not display this activity. Since many proteins contact helix 2 of TBP, this provides a molecular basis for mutually exclusive TBP interactions and stresses the importance of this structural element for eukaryotic transcription

Outcome of Colonic Surgery in Elderly Patients with Colon Cancer

Introduction. Colonic cancer is one of the most commonly diagnosed malignancies and most often occurs in patients aged 65 years or older. Aim. To evaluate the outcome of colonic surgery in the elderly in our hospital and to compare five-year survival rates between the younger and elderly patients. Methods. 207 consecutive patients underwent surgery for colon cancer. Patients were separated in patients younger than 75 and older than 75 years. Results. Elderly patients presented significantly more (P < .05) as a surgical emergency, had a longer duration of admission and were more often admitted to the ICU (P < .01). Also, elderly patients had significant more co-morbidities, especially cardiovascular pathology (P < .01). Post-operative complications were seen more often in the elderly, although no significant difference was seen in anastomotic leakage. The five-year survival rate in the younger group was 62% compared with 36% in the elderly (P < .05). DFS was 61% in the younger patients compared with 32% in the elderly (P < .05). Conclusion. Curative resection of colonic carcinoma in the elderly is well tolerated and age alone should not be an indication for less aggressive therapy. However, the type and number of co-morbidities influence post-operative mortality and morbidity

Variations in activin receptor, inhibin/activin subunit and follistatin mRNAs in human prostate tumour tissues

The possible role of activin in the regulation of malignant prostatic growth was studied using RNAase protection assays of activin receptors, inhibin/activin subunits and follistatin mRNAs in the human prostatic carcinoma cell lines LNCaP-FGC, -R and -LNO, in human prostatic carcinoma xenografts and in human prostatic tissue. Activin receptor types IA (ActRIA), IB (ActRIB), IIA (ActRIIA) and IIB (ActRIIB) mRNAs were generally expressed in prostate pithelial cells, with significantly lower levels of ActRIB mRNA in prostate tumour aterial when compared to non-malignant tissue (P< 0.05; Mann–Whitney U -test). Inhibin/activin βA- and βB-subunit mRNA expression was also found in prostate tissue. Androgen-independent xenografts expressed significantly lower amounts of βB-subunit mRNA when compared to androgen-dependent xenografts (P< 0.05). While βB-subunit mRNA was expressed by LNCaP-FGC and -LNO cells, virtually no expression was found in the androgen-independent LNCaP-R line. Inhibin α-subunit mRNA levels were low or undetectable in all samples investigated. Follistatin mRNA was undetectable in LNCaP-sublines, while low levels were found in prostatic tissues. In androgen-independent LNCaP-R cells, activin inhibited cell growth in a dose-dependent manner. These results suggest that prostate tumour progression is accompanied by a decrease of the inhibitory effect of locally produced activin by either a decrease in the expression of activin βB-subunit mRNA or by a decrease of ActRIB mRNA levels. © 2000 Cancer Research Campaig

Exploring the components, asymmetry and distribution of relationship quality in wild Barbary macaques (Macaca sylvanus)

Social relationships between group members are a key feature of many animal societies. The quality of social relationships has been described by three main components: value, compatibility and security, based on the benefits, tenure and stability of social exchanges. We aimed to analyse whether this three component structure could be used to describe the quality of social relationships in wild Barbary macaques (Macaca sylvanus). Moreover, we examined whether relationship quality was affected by the sex, age and rank differences between social partners, and investigated the asymmetric nature of social relationships. We collected over 1,900 hours of focal data on seven behavioural variables measuring relationship quality, and used principal component analysis to investigate how these variables clustered together. We found that relationship quality in wild Barbary macaques can be described by a three component structure that represents the value, compatibility and security of a relationship. Female-female dyads had more valuable relationships and same-age dyads more compatible relationships than any other dyad. Rank difference had no effect on the quality of a social relationship. Finally, we found a high degree of asymmetry in how members of a dyad exchange social behaviour. We argue that the asymmetry of social relationships should be taken into account when exploring the pattern and function of social behaviour in animal societies

Effectiveness of supported self-help in recurrent depression: a randomized controlled trial in primary care

Background: The burden and economic consequences of depression are high, mostly due to its recurrent nature. Due to current budget and time restraints, a preventive, low-cost, accessible minimal intervention is much needed. In this study, we evaluated the effectiveness of a supported self-help preventive cognitive therapy (S-PCT) added to treatment as usual (TAU) in primary care, compared to TAU alone. Methods: We conducted a randomized controlled trial among 248 patients with a history of depression, currently in full or partial remission or recovery. Participants were randomized to TAU augmented with S-PCT (n = 124) or TAU alone (n = 124). S-PCT consisted of an 8-week self-help intervention, supported by weekly telephone guidance by a counselor. The intervention included a self-help book that could be read at home. The primary outcome was the incidence of relapse or recurrence and was assessed over the telephone by the Structured Clinical Interview for DSM-IV axis 1 disorders. Participants were observed for 12 months. Secondary outcomes were depressive symptoms, quality of life (EQ-5D and SF-12), comorbid psychopathology, and self-efficacy. These secondary outcomes were assessed by digital questionnaires. Results: In the S-PCT group, 44 participants (35.5) experienced a relapse or recurrence, compared to 62 participants (50.0) in the TAU group (incidence rate ratio = 0.71, 95 CI 0.52-0.97; risk difference = 14, 95 CI 2-24, number needed to treat = 7). Compared to the TAU group, the S-PCT group showed a significant reduction in depressive symptoms over 12 months (mean difference-2.18; 95 CI-3.09 to-1.27) and a significant increase in quality of life (EQ-5D) (mean difference 0.04; 95 CI 0.004-0.08). S-PCT had no effect on comorbid psychopathology, self-efficacy, and quality of life based on the SF-12. Conclusions: A supported self-help preventive cognitive therapy, guided by a counselor in primary care, proved to be effective in reducing the burden of recurrent depression

Payoff- and Sex-Biased Social Learning Interact in a Wild Primate Population.

Social learning in animals is now well documented, but few studies have determined the contexts shaping when social learning is deployed. Theoretical studies predict copying of conspecifics gaining higher payoffs [1-4], a bias demonstrated in primates only in captivity [5]. In the wild, research has shown selective attention toward the philopatric sex, a group's stable core [6]. Here, we report the first rigorous experimental test of the existence of a payoff bias in wild primates and its interaction with the sex of the model. We created a payoff bias in which an immigrant alpha male in each of three groups of wild vervet monkeys received five times more food upon opening a foraging box than did the philopatric alpha female, whereas in two control groups, male and female models received the same amount of food. We tested whether this payoff asymmetry would override the previously documented selective learning from resident females. Group members were tested after having watched both models. When both models received the same amount of food, audience members copied the female model significantly more than the male model, confirming previous findings. However, when a marked payoff bias was introduced, male, but not female, vervet monkeys significantly more often copied the male model receiving a higher payoff. These results demonstrate behavioral flexibility in the dispersing sex in these primates and suggest that the philopatric sex can afford to be more conservative in their social learning. Our findings show that multiple social-learning biases can coexist and interact within the same species

Glycoprotein Nonmetastatic Melanoma Protein B as Potential Imaging Marker in Posttherapeutic Metastatic Head and Neck Cancer

OBJECTIVE: To evaluate expression of potential molecular imaging targets epidermal growth factor receptor (EGFR), glycoprotein nonmetastatic melanoma protein B (GPNMB), and vascular endothelial growth factor (VEGF) in lymph nodes (LNs) with or without head and neck squamous cell carcinoma (HNSCC) metastases after (chemo)radiation. STUDY DESIGN: Retrospective study comparing receptor expression in paired lymph nodes after initial treatment. SETTING: A tertiary referral hospital. SUBJECTS AND METHODS: Salvage neck dissection specimens of 40 patients treated with (chemo)radiation were selected. LNs that contained viable tumor, reactive changes after initial treatment, and normal LNs were analyzed using immunohistochemically determined H-scores and by calculating sensitivity and specificity rates and positive/negative predictive values (PPVs/NPVs). RESULTS: EGFR expression was found in 86% and GPNMB expression in 100% of the LNs with viable tumor. VEGF expression was present in all lymph node types. For EGFR, the sensitivity rate was 86%, and specificity rate was 81%. For GPNMB, these were 100% and 75%, respectively. PPV of EGFR was 61.8% and NPV was 98.2%. These were 56.4% and 100% for GPNMB, respectively. CONCLUSION: In residual or recurrent HNSCC lymph node metastases, both EGFR and GPNMB show tumor-specific expression in immunohistochemistry, which may prove useful in future molecular imaging in salvage neck dissections. Immunohistochemically detected VEGF expression indicates that this target is not feasible for imaging purposes in salvage surgery. Therefore, GPNMB could be a new potential imaging target showing comparable results to EGFR in immunohistochemistry

Seasonal effects on reconciliation in Macaca Fuscata Yakui

Dietary composition may have profound effects on the activity budgets, levelof food competition, and social behavior of a species. Similarly, in seasonally breeding species, the mating season is a period in which competition for mating partners increases, affecting amicable social interactions among group members. We analyzed the importance of the mating season and of seasonal variations in dietary composition and food competition on econciliation in wild female Japanese macaques (Macaca fuscata yakui) on Yakushima Island, Japan. Yakushima macaques are appropriate subjects because they are seasonal breeders and their dietary composition significantly changes among the seasons. Though large differences occurred between the summer months and the winter and early spring months in activity budgets and the consumption of the main food sources, i.e., fruits, seeds, and leaves, the level of food competition and conciliatory tendency remained unaffected. Conversely,conciliatory tendency is significantly lower during the mating season than in the nonmating season. Moreover, conciliatory tendency is lower when 1 or both female opponents is in estrous than when they are not. Thus the mating season has profound effects on reconciliation, whereas seasonal changes in activity budgets and dietary composition do not. The detrimental effects of the mating season on female social relationships and reconciliation may be due to the importance of female competition for access to male partners in multimale, multifemale societies

A supported self-help for recurrent depression in primary care; an economic evaluation alongside a multi-center randomised controlled trial

Background Major depression is a prevalent mental disorder with a high risk of relapse or recurrence. Only few studies have focused on the cost-effectiveness of interventions aimed at the prevention of relapse or recurrence of depression in primary care. Aim To evaluate the cost-effectiveness of a supported Self-help Preventive Cognitive Therapy (S-PCT) added to treatment-as-usual (TAU) compared with TAU alone for patients with a history of depression, currently in remission. Methods An economic evaluation alongside a multi-center randomised controlled trial was performed (n = 248) over a 12-month follow-up. Outcomes included relapse or recurrence of depression and quality-adjusted-life-years (QALYs) based on the EuroQol-5D. Analyses were performed from both a societal and healthcare perspective. Missing data were imputed using multiple imputations. Uncertainty was estimated using bootstrapping and presented using the cost-effectiveness plane and the Cost- Effectiveness Acceptability Curve (CEAC). Cost estimates were adjusted for baseline costs. Results S-PCT statistically significantly decreased relapse or recurrence by15% (95%CI 3;28) compared to TAU. Mean total societal costs were €2,114 higher (95%CI -112;4261). From a societal perspective, the ICER for recurrence of depression was 13,515. At a Willingness To Pay (WTP) of 22,000 €/recurrence prevented, the probability that S-PCT is cost-effective, in comparison with TAU, is 80%. From a healthcare perspective, the WTP at a probability of 80% should be 11,500 €/recurrence prevented. The ICER for QALYs was 63,051. The CEA curve indicated that at a WTP of 30,000 €/QALY gained, the probability that S-PCT is cost-effective compared to TAU is 21%. From a healthcare perspective, at a WTP of 30,000 €/QALY gained, the probability that S-PCT is cost-effective compared to TAU is 46%. Conclusions Though ultimately depending on the WTP of decision makers, we expect that for both relapse or recurrence and QALYs, S-PCT cannot be considered cost-effective compared to TAU