Analyzing the correlation between protein expression and sequence-related features of mRNA and protein in Escherichia coli K-12 MG1655 model.

It was necessary to have a tool that could predict the amount of protein and optimize the gene sequences to produce recombinant proteins efficiently. The Transim model published by Tuller et al. in 2018 can calculate the translation rate in E. coli using features on the mRNA sequence, achieving a Spearman correlation with the amount of protein per mRNA of 0.36 when tested on the dataset of operons' first genes in E. coli K-12 MG1655 genome. However, this Spearman correlation was not high, and the model did not fully consider the features of mRNA and protein sequences. Therefore, to enhance the prediction capability, our study firstly tried expanding the testing dataset, adding genes inside the operon, and using the microarray of the mRNA expression data set, thereby helping to improve the correlation of translation rate with the amount of protein with more than 0.42. Next, the applicability of 6 traditional machine learning models to calculate a "new translation rate" was examined using initiation rate and elongation rate as inputs. The result showed that the SVR algorithm had the most correlated new translation rates, with Spearman correlation improving to R = 0.6699 with protein level output and to R = 0.6536 with protein level per mRNA. Finally, the study investigated the degree of improvement when combining more features with the new translation rates. The results showed that the model's predictive ability to produce a protein per mRNA reached R = 0.6660 when using six features, while the correlation of this model's final translation rate to protein level was up to R = 0.6729. This demonstrated the model's capability to predict protein expression of a gene, rather than being limited to predicting expression by an mRNA and showed the model's potential for development into gene expression predicting tools.

Development of Artificial Intelligence-Teaching Assistant System for Undergraduate Nursing Students: A Field-Testing Study.

Keeping students engaged and motivated during online or class discussion may be challenging. Artificial intelligence has potential to facilitate active learning by enhancing student engagement, motivation, and learning outcomes. The purpose of this study was to develop, test usability of, and explore undergraduate nursing students' perceptions toward the Artificial Intelligence-Teaching Assistant System. The system was developed based on three main components: machine tutor intelligence, a graphical user interface, and a communication connector. They were included in the system to support contextual machine tutoring. A field-testing study design, a mixed-method approach, was utilized with questionnaires and focus group interview. Twenty-one undergraduate nursing students participated in this study, and they interacted with the system for 2 hours following the required activity checklist. The students completed the validated usability questionnaires and then participated in the focus group interview. Descriptive statistics were used to analyze quantitative data, and thematic analysis was used to analyze qualitative data from the focus group interviews. The results showed that the Artificial Intelligence-Teaching Assistant System was user-friendly. Four main themes emerged, namely, functionality, feasibility, artificial unintelligence, and suggested learning modality. However, Artificial Intelligence-Teaching Assistant System functions, user interface, and content can be improved before full implementation.

Preparation of Bacillus subtilis cell samples and generation of an SDS-PAGE.

Bacillus subtilis is a critical host for producing recombinant proteins. However, the SDS-PAGE process, including the sample preparation steps, varies among B. subtilis-related studies, making it impossible to compare findings. Hence, this paper provides a simple guide to culture and collect B. subtilis cells through an OD600 measurement and a protocol for SDS-PAGE. These techniques were applied to check the expression of a BgaB, a reporter protein and LukF-PV, a potential vaccine candidate against S. aureus, in the cytoplasm of B. subtilis under the control of a strong promoter, Pgrac212. This protocol could be helpful for scientists in preparing samples and generating an SDS-PAGE experiment, as well as favoring the unification of research about protein expression in B. subtilis.

The characteristics and acceptance of Technology-Enabled diabetes prevention programs (t-DPP) amongst individuals with prediabetes: A scoping review.

AIM AND OBJECTIVE: As rising global prevalence of diabetes burdens an overstrained healthcare system, it would be prudent to employ primary prevention strategies. This review aims to detail characteristics of technology-enabled diabetes prevention programs (t-DPP) and the technology acceptance amongst prediabetic individuals. DESIGN: A scoping review. REVIEW METHODS: Summative and direct content analysis. DATA SOURCES: Seven electronic databases-PubMed, Cochrane, Embase, CINAHL, Scopus, PsycINFO and Web of Science-were searched from inception till 9 June 2022 for primary studies conducted on t-DPP. Initial search identified 2412 unique articles. Removal of duplicates and irrelevant articles resulted in 58 full text articles screened and 17 articles meeting the eligibility criteria. There was no limitation to study type or year of publication, but language was limited to English. RESULTS: Common t-DPP characteristics include physical activity (n = 17), diet control (n = 16), coaching (n = 12), social support (n = 9) and skills acquisition (n = 12). Technological acceptance of t-DPPs were generally positive as participants found them useful (n = 5) and easy to use (n = 4), with majority of the participants interested (n = 5) and engaging well with it (n = 13). However, personal-, design- and technological-level factors were found to negatively influence t-DPPs acceptance. CONCLUSION: This review reported a generally positive technological acceptance. The result encourages remote delivery of diabetes prevention programs, offering researchers a guide to t-DPP development. However, it also highlights the need for integration of behavioural change theories and socio-cultural considerations, with gaps in knowledge amongst men and young adults. IMPLICATIONS FOR NURSING: The success of t-DPP can reinforce clinical advice and sustain health behaviours advocated by nurses. Involvement of diabetes-trained nurses would enable continual risk assessment, monitoring and timely intervention to prevent diabetes and potential complications. REPORTING METHOD: PRISMA-ScR checklist.

Utilizing educational technology in enhancing undergraduate nursing students' engagement and motivation: A scoping review.

BACKGROUND: Modern educational technology (Edtech) combines technological tools with educational theories. Over the years, Edtech has been adopted in nursing education to address student needs and expectations, institutional resources, community stakeholder expectations, and healthcare trends. However, regardless of the technologies used, keeping students engaged in learning is still challenging. As intrinsic motivation is significantly related to academic achievement, ensuring student engagement and motivation for learning becomes crucial. AIMS: This scoping review aims to explore the types and features of modern Edtech that have impacted on undergraduate nursing students' engagement and motivation. DESIGN: This scoping review is based on the five-stage approach following Arksey and O'Malley's framework, and the Engagement theory framework for technology-based teaching and learning. METHODS: A systemic search was conducted across 10 electronic databases (PubMed, EMBASE, CINAHL, PsycINFO, ProQuest, Web of Science, Cochrane, Engineering Village, and IEEE Explore). The titles, abstracts, and full texts were screened and reviewed based on the inclusion criteria of undergraduate nursing students, using innovative Edtech, and outcomes of engagement and motivation. Studies published in non-peer reviewed journals, or not in English were excluded. Study characteristics were summarized and quantified. Descriptions of educational technology characteristics from selected studies were coded and categorized as follows: "Facilitating collaboration", "Stimulating problem-solving", and "Pursuing authentic focus". RESULTS: Majority of the studies utilised gamification over other types of Edtech such as virtual reality or smart glasses, successfully engaging and motivating students through the features of collaboration, competition, and challenge. Despite the high technology aspect of the interventions used, the human presence as an authentic focus was perceived to be important in engaging students in learning experience. Moreover, attaining meaningful achievements also improves engagement and motivation. CONCLUSIONS: Edtech can promote positive engagement and motivation of undergraduate nursing students. Educators should emphasize an authentic focus in students' learning experience with Edtech.

A Cough-based deep learning framework for detecting COVID-19.

This paper presents a deep learning framework for detecting COVID-19 positive subjects from their cough sounds. In particular, the proposed approach comprises two main steps. In the first step, we generate a feature representing the cough sound by combining an embedding extracted from a pre-trained model and handcrafted features extracted from draw audio recording, referred to as the front-end feature extraction. Then, the combined features are fed into different back-end classification models for detecting COVID-19 positive subjects in the second step. Our experiments on the Track-2 dataset of the Second 2021 DiCOVA Challenge achieved the second top ranking with an AUC score of 81.21 and the top F1 score of 53.21 on a Blind Test set, improving the challenge baseline by 8.43% and 23.4% respectively and showing deployability, robustness and competitiveness with the state-of-the-art systems.

Effectiveness of a nurse-led smartphone-based self-management programme for people with poorly controlled type 2 diabetes: A randomized controlled trial.

AIM: To evaluate the effectiveness of a nurse-led smartphone-based self-management programme (NSSMP) on improving self-efficacy, promoting diabetes self-care, increasing health-related quality of life (HRQoL) and decreasing HbA1c, acute complications and unplanned medical consultation for people with poorly controlled type 2 diabetes compared with a nurse-led diabetic service (NDS). DESIGN: A two-arm randomized controlled trial with repeated measures was conducted. METHODS: Participants were recruited from June 2018 to September 2020. Eligible participants were assigned to either the intervention or control group randomly. Participants assigned to intervention group received the 6-month NSSMP, while those in the control group received existing NDS provided by the study hospital. Outcomes were measured at baseline, and at 3 and 6 months from baseline. RESULTS: A total of 114 participants were recruited. There were no significant interactions between group and time for all the outcomes except for blood glucose testing activities (F = 4.742, p = .015). Both groups had reduced HbA1c over 6 months. The intervention group had a lower HbA1c than the control group at follow-ups, but the differences were not statistically significant. None of the participants had acute diabetes complications at follow-up. Similarly, the differences in the number of unplanned medical consultation at 6-month follow-up between two groups were statistically insignificant. CONCLUSION: The NSSMP is as effective as existing NDS provided by the study hospital in improving most of the outcomes. NSSMP can liberate valuable time for nurses to provide care to critically ill patients and supports healthcare resource constraints in the current COVID-19 pandemic. IMPACT: The existing diabetes service is labour intensive as nurses are required to deliver education, follow-up telephone calls to trace blood sugar monitoring and provide therapeutic consultations and necessary referrals. The outbreak of COVID-19 pandemic has added further strain on the overworked professionals. NSSMP provides an alternative programme that is just as effective, to reduce nurses' workload by delegating them back to the individuals through self-management strategies. This enables nurses to increase contact time with patients, and individuals to take onus of their disease through increased self-efficacy, facilitated by technology. CLINICAL TRIAL: This study is registered under clinical registration number NCT03088475.

A Protocol to Enhance Soluble Protein Expression in the Cytoplasm of Bacillus subtilis.

Bacillus subtilis is a generally regarded as safe (GRAS) microorganism, which has been used for industrial production of recombinant enzymes. Many inducible and inducer-free expression vectors have been developed for intracellular production; some of those demonstrated the capability for protein expression up to 42% of total cellular proteins. In this chapter, we introduce the method to enhance the expression of soluble protein in B. subtilis. It includes the construction of vectors, the transformation of a plasmid into B. subtilis, and checking the expression of the protein.

The effectiveness of a nurse-led home-based heart failure self-management programme (the HOM-HEMP) for patients with chronic heart failure: A three-arm stratified randomized controlled trial.

BACKGROUND: Although important, heart failure self-care remains a challenge for many patients. This study aimed to evaluate the effect of a nurse-led, home-based self-management psychosocial education intervention (HOM-HEMP). The primary outcome was patient's HF self-care in terms of maintenance, management and confidence. The secondary outcomes were cardiac self-efficacy, psychological wellbeing in terms of perceived social support, health related quality of life and levels of anxiety and depression. The clinical outcomes included New York Heart Association (NYHA) functional class and numbers of unplanned health service visits due to cardiac-related reasons. DESIGN: A three-arm stratified randomized controlled trial was conducted (Clinical trial registration number: NCT03108235). METHODS: A total of 213 participants admitted for heart failure were recruited from the inpatient wards of a tertiary public hospital in Singapore. They were randomly allocated to the control group, the experimental group A or the experimental group B. All participants received the usual care provided by the hospital. Participants in experimental groups A and B received the HOM-HEMP intervention, and those in experimental group B received an additional supplemental smartphone application. Data were collected at baseline, 6 weeks, 3 months and 6 months from baseline. RESULTS: Compared to the control groups, participants in either of the experimental group had significantly higher levels of heart failure self-care maintenance (F = 4.222, p = 0.001), self-care confidence (F = 5.796, p < 0.001) and self-care management (p < 0.05) at 6-week, 3-month and 6-month follow-ups. In addition, both experimental groups had significantly higher levels of cardiac self-efficacy, better health related quality of life and lower depression levels than the control group after the study intervention. A higher proportion of participants in both experimental groups had a better New York Heart Association functional class at 6-week and 3-month follow-ups. Participants in the experimental group B also had significantly fewer cardiac-related unplanned hospital admissions and emergency room visits than the control group at 6-month follow-up. Results on perceived social support were not significant. The study outcomes in experimental group A and B were not significantly different at any of the post intervention follow-up. CONCLUSION: The findings suggested that HOM-HEMP is an effective intervention for patients with heart failure in Singapore.

TP53 Mutations and Outcomes in Breast Cancer: Reading beyond the Headlines.

TP53 is the most frequently mutated gene in breast cancer, but its role in survival is confounded by different studies concluding that TP53 mutations are associated with negative, neutral, or positive outcomes. Closer examination showed that many studies were limited by factors such as imprecise methods to detect TP53 mutations and small cohorts that combined patients treated with drugs having very different mechanisms of action. When only studies of patients receiving the same treatment(s) were compared, they tended to agree. These analyses reveal a role for TP53 in response to different treatments as complex as its different biological activities. We discuss studies that have assessed the role of TP53 mutations in breast cancer treatment and limitations in interpreting reported results.

The development and pilot study of a nurse-led HOMe-based HEart failure self-Management Programme (the HOM-HEMP) for patients with chronic heart failure, following Medical Research Council guidelines.

BACKGROUND: Chronic heart failure (CHF) is one of the most common causes of hospital admissions and readmissions. Managing CHF requires a comprehensive treatment plan that consists of medication treatment and behavioural change. However, patients often feel unprepared for their self-management role in the community, especially during the period of transition after discharge from hospital. Therefore, an effective intervention to promote CHF self-management is needed. AIMS: This paper describes the development and pilot testing of a multicomponent nursing intervention (i.e. the HOM-HEMP) for a randomised controlled trial to assess its effectiveness in improving self-care behaviour among CHF patients in Singapore. A description of the study intervention is also delineated in detail. METHODS: The HOM-HEMP was developed based on the UK Medical Research Council framework for developing and evaluating complex interventions. After the development of the study intervention, a single group pre- and post-repeated measure pilot test was conducted to evaluate the study intervention package for its acceptability and the feasibility of the data collection procedure. Ten participants were recruited through consecutive sampling. All of the participants received the full intervention package with the supplementary mobile application. The data were collected at baseline and immediately after the study intervention (i.e. 6 weeks from baseline). The outcome measures included the Self-Care Heart Failure Index, Cardiac Self-Efficacy Scale, Minnesota Living with Heart Failure Questionnaire, Hospital Anxiety and Depression Scale and Short Form of the Social Support Questionnaire. RESULTS: The results from the pilot testing showed that the programme was feasible and potentially effective in improving patient's self-care management, psychological outcomes and health-related quality of life. CONCLUSION: A self-management psychosocial education approach is the preferred choice for many patients with chronic diseases. The effectiveness of the HOM-HEMP will next be tested in a full scale randomised control trial.

Effect of a mHealth programme on coronary heart disease prevention among working population in Singapore: A single group pretest-post-test design.

AIM: The aim of this study was to develop and examine the effectiveness of a 4-week Mobile Health (mHealth) programme using the smartphone app Care4Heart on awareness, knowledge, perceived stress, and a heart-related lifestyle among working population in Singapore. DESIGN: A quasi-experimental single group pretest and repeated post-test design. METHODS: A total of 160 nonhealth-related working adults were recruited from February 2016-April 2016. The Care4Heart app was installed on the participants' phones. Outcome measures, including the Heart Disease Fact Questionnaire-2, the Behavioral Risk Factor Surveillance System, and the Perceived Stress Scale were collected online at baseline, 4th week, and 6th month from baseline. RESULTS: Compared with the baseline, the participants had significantly higher total mean scores for awareness and knowledge of coronary heart disease (CHD) after study intervention at 4 weeks and 6 months from baseline. However, there were no significant differences in perceived stress levels and heart-related lifestyle behaviours before and after the intervention. CONCLUSIONS: The study contributed some evidence that the mHealth app helped to improve awareness and knowledge of CHD. IMPACT: Coronary heart disease remains one of the major causes of death and disability. It imposes a heavy financial burden on working adults. However, working adults were less able to identify the risk factors and adopt healthy lifestyles due to gaps in knowledge and awareness. This study demonstrated some effects of a mHealth programme in improving awareness and knowledge of CHD among the working population. mHealth provides a potential avenue for primary prevention of CHD.

The effect of a smartphone-based coronary heart disease prevention (SBCHDP) programme on awareness and knowledge of CHD, stress, and cardiac-related lifestyle behaviours among the working population in Singapore: a pilot randomised controlled trial.

BACKGROUND: Coronary heart disease (CHD) is the most prevalent type of cardiac disease among adults worldwide, including those in Singapore. Most of its risk factors, such as smoking, physical inactivity and high blood pressure, are preventable. mHealth has improved in the last decade, showing promising results in chronic disease prevention and health promotion worldwide. Our aim was to develop and examine the effect of a 4-week Smartphone-Based Coronary Heart Disease Prevention (SBCHDP) programme in improving awareness and knowledge of CHD, perceived stress as well as cardiac-related lifestyle behaviours in the working population of Singapore. METHODS: The smartphone app "Care4Heart" was developed as the main component of the programme. App content was reviewed and validated by a panel of experts, including two cardiologists and two experienced cardiology-trained nurses. A pilot randomised controlled trial was conducted. Eighty working people were recruited and randomised to either the intervention group (n = 40) or the control group (n = 40). The intervention group underwent a 4-week SBCHDP programme, whereas the control group were offered health promotion websites only. The participants' CHD knowledge, perceived stress and behavioural risk factors were measured at baseline and on the 4th week using the Heart Disease Fact Questionnaire-2, Perceived Stress Scale, and Behavioural Risk Factor Surveillance System. RESULTS: After the SBCHDP programme, participants in the intervention group had a better awareness of CHD being the second leading cause of death in Singapore (X 2 = 6.486, p = 0.039), a better overall CHD knowledge level (t = 3.171, p = 0.002), and better behaviour concerning blood cholesterol control (X 2 = 4.54, p = 0.033) than participants in the control group. CONCLUSION: This pilot study partially confirmed the positive effects of the SBCHDP programme in improving awareness and knowledge of CHD among the working population. Due to the small sample size and short follow-up period, this study was underpowered to detect significant differences between groups. A full-scale longitudinal study is required in the future to confirm the effectiveness of the SBCHDP programme.

Monitoring Conformational Changes in the Receptor Tyrosine Kinase EGFR.

The receptor tyrosine kinase EGFR is regulated by complex conformational changes, and this conformational control is disturbed in certain types of cancer. Many ligands are known to bind EGFR in its active conformation, thereby preventing ATP from binding. Only a few ligands are known to stabilize EGFR in its inactive conformation, thus providing novel strategies for perturbing EGFR activity. We report a direct binding assay that enables the identification of novel ligands that bind to and stabilize the inactive conformation of EGFR.

Discovery of inter-domain stabilizers-a novel assay system for allosteric akt inhibitors.

In addition to the catalytically active kinase domain, most kinases feature regulatory domains that govern their activity. Modulating and interfering with these interdomain interactions presents a major opportunity for understanding biological systems and developing novel therapeutics. Therefore, small molecule inhibitors that target these interactions through an allosteric mode of action have high intrinsic selectivity, as these interactions are often unique to a single kinase or kinase family. Here we report the development of iFLiK (interface-Fluorescent Labels in Kinases), a fluorescence-based assay that can monitor such interdomain interactions. Using iFLiK, we have demonstrated selective detection of allosteric Akt inhibitors that induce an inactive closed conformation unique to Akt. This methodology easily distinguished small molecule allosteric inhibitors from classic ATP-competitive inhibitors. Screening an in-house compound library with iFLiK, we were able to identify novel compounds with a scaffold that has not been previously described for allosteric Akt inhibitors.

Identification of type II and III DDR2 inhibitors.

Discoidin domain-containing receptors (DDRs) exhibit a unique mechanism of action among the receptor tyrosine kinases (RTKs) because their catalytic activity is induced by extracellular collagen binding. Moreover, they are essential components in the assimilation of extracellular signals. Recently, DDRs were reported to be significantly linked to tumor progression in breast cancer by facilitating the processes of invasion, migration, and metastasis. Here, we report the successful development of a fluorescence-based, direct binding assay for the detection of type II and III DFG-out binders for DDR2. Using sequence alignments and homology modeling, we designed a DDR2 construct appropriate for fluorescent labeling. Successful assay development was validated by sensitive detection of a reference DFG-out binder. Subsequent downscaling led to convenient application to high-throughput screening formats. Screening of a representative compound library identified high-affinity DDR2 ligands validated by orthogonal activity-based assays, and a subset of identified compounds was further investigated with respect to DDR1 inhibition.

Proline primed helix length as a modulator of the nuclear receptor-coactivator interaction.

Nuclear receptor binding to coactivator proteins is an obligate first step in the regulation of gene transcription. Nuclear receptors preferentially bind to an LXXLL peptide motif which is highly conserved throughout the 300 or so natural coactivator proteins. This knowledge has shaped current understanding of this fundamental protein-protein interaction, and continues to inspire the search for new drug therapies. However, sequence specificity beyond the LXXLL motif and the molecular functioning of flanking residues still requires urgent addressing. Here, ribosome display has been used to reassess the estrogen receptor for new and enlarged peptide recognition motifs, leading to the discovery of a potent and highly evolved PXLXXLLXXP binding consensus. Molecular modeling and X-ray crystallography studies have provided the molecular insights on the role of the flanking prolines in priming the length of the α-helix and enabling optimal interactions of the α-helix dipole and its surrounding amino acids with the surface charge clamp and the receptor activation function 2. These findings represent new structural parameters for modulating the nuclear receptor-coactivator interaction based on linear sequences of proteinogenic amino acids and for the design of chemically modified inhibitors.

Reversible and oriented immobilization of ferrocene-modified proteins.

Adopting supramolecular chemistry for immobilization of proteins is an attractive strategy that entails reversibility and responsiveness to stimuli. The reversible and oriented immobilization and micropatterning of ferrocene-tagged yellow fluorescent proteins (Fc-YFPs) onto ß-cyclodextrin (ßCD) molecular printboards was characterized using surface plasmon resonance (SPR) spectroscopy and fluorescence microscopy in combination with electrochemistry. The proteins were assembled on the surface through the specific supramolecular host-guest interaction between ßCD and ferrocene. Application of a dynamic covalent disulfide lock between two YFP proteins resulted in a switch from monovalent to divalent ferrocene interactions with the ßCD surface, yielding a more stable protein immobilization. The SPR titration data for the protein immobilization were fitted to a 1:1 Langmuir-type model, yielding K(LM) = 2.5 × 10(5) M(-1) and K(i,s) = 1.2 × 10(3) M(-1), which compares favorably to the intrinsic binding constant presented in the literature for the monovalent interaction of ferrocene with ßCD self-assembled monolayers. In addition, the SPR binding experiments were qualitatively simulated, confirming the binding of Fc-YFP in both divalent and monovalent fashion to the ßCD monolayers. The Fc-YFPs could be patterned on ßCD surfaces in uniform monolayers, as revealed using fluorescence microscopy and atomic force microscopy measurements. Both fluorescence microscopy imaging and SPR measurements were carried out with the in situ capability to perform cyclic voltammetry and chronoamperometry. These studies emphasize the repetitive desorption and adsorption of the ferrocene-tagged proteins from the ßCD surface upon electrochemical oxidation and reduction, respectively.

Estrogen receptor α/ß-cofactor motif interactions; interplay of tyrosine 537/488 phosphorylation and LXXLL motifs.

The Estrogen Receptors ERα and ERß bind cofactor proteins via short LXXLL motifs. The exact regulation and selectivity of these interactions remains an open question and the role of post-translational modifications (PTMs) is virtually unexplored. Here, we designed an X(7)-LXXLL-X(7) T7 phage display library and screened this against four ER protein constructs: the 'naked' ERα and ERß Ligand Binding Domains (LBDs) and the tyrosine phosphorylated ERα (pY537) and ERß (pY488) LBDs. The site-selective tyrosine phosphorylated protein constructs were obtained via a protein semi-synthesis approach. Phage display screening yielded preferential sets of peptides. LXXLL peptides with a low pI/acidic C-terminus prefer binding to the naked ERß over the phosphorylated ERß analogue and ERα constructs. Peptides with a high pI/basic C-terminus show the opposite behaviour. These findings not only show regulation of the ERß-cofactor interaction via tyrosine phosphorylation, but also suggest that ERß and its tyrosine 488 phosphorylation play crucial roles in modulating interactions of coactivators to ERα since the natural Steroid Receptor Coactivators (SRCs) feature LXXLL motifs with acidic C-termini, while the repressor protein RIP140 features LXXLL motifs with basic C-termini. This insight provides explanation for ER transcriptional activity and can lead to more focussed targeting of the ER-coactivator interaction.