Analysis on the BAK1-interacting RLKs BIR2 and BIR3, two proteins that differentially regulate BAK1-dependent pathways

BAK1 is a multifunctional co-receptor that positively regulates multiple plant signaling pathways by interacting with the corresponding ligand-binding receptors, e.g. BRI1, FLS2, EFR, PEPR1 and PEPR2. Moreover, BAK1 plays a role in cell death control. In order to investigate how BAK1 is regulated we purified in vivo BAK1 complexes and identified two new BAK1 interactors, the BAK1 interacting RLKs 2 and 3 (BIR2 and BIR3). Functional analysis of bir2 mutants showed that they are hyperresponsive to MAMP treatment, show cell death spreading after pathogen infection but are not impaired in BL signaling. In this study the molecular mechanism how BIR2 regulates MAMP responses was further investigated. With Co-IP analysis in Arabidopsis wildtype plants it was shown that treatment with flg22 leads to a partial release of BAK1 from BIR2. Treatment with a cocktail of flg22, elf18, BL and Atpep1 leads to increased release of BAK1 from BIR2 compared to single treatments, indicating that BAK1 exists in preformed complexes with different ligand-binding receptors. Functional analyses of 35S-BIR3 plants have shown that BIR3 is a negative regulator of BL responses, MAMP responses and cell death. In this study the role of BIR3 in BL responses was further investigated and it could be shown that BIR3 not only interacts with BAK1 but also shows direct interaction with the ligand-binding receptor BRI1. The involvement of BIR3 in MAMP responses was confirmed with different functional assays. On the molecular level it was shown that BIR3 interacts with BAK1 and FLS2 and regulates BAK1-FLS2 complex formation. bak1 bir3 double mutants show a strong growth phenotype with spontaneous lesion formation and strong cell death spreading after A. brassicicola infections, confirming the involvement of BIR3 in cell death regulation. To investigate the relationship of the closely related proteins BIR2 and BIR3, bir2-1 35S-BIR3 plants were used. It was shown that BIR2 and BIR3 are partially redundant but BIR2 seems to masks the BIR3 function in the wildtype situation and to have a stronger impact on the MAMP and cell death pathway

Impactful by design: exploring a New Product Development (NPD) framework for socially responsible technology

Researchers observed that digital products and services, such as social networking sites and online and mobile games, play a role in enticing users in ways that ensure increases in revenue of their providers. At the same time, with the advent of several disruptive new technology products in the not-so-distant future,including artificial intelligence-powered robots, drones and virtual reality, the boundary of ethically acceptable practices for the society by the technology companies is becoming an increasing topic of concern. Recent evidences show that technology companies and public organisations often find themselves in disagreement about what innovative features should be rolled out. This practice-based MPhil thesis explores the potential of integrating a social stakeholder into a cross-functional New Product Development (NPD) team that comprises stakeholders in viability, feasibility, desirability and social responsibility. The public adoption and the commercial potential of the project outcome shows that the proposed NPD framework would be useful for the production of socially responsible technology products. In order to inform the technology and design communities as well as public services, the research looks at participants’ gains raised by mutual exchanges of the participating stakeholders as well as identifying building blocks for the successful execution of such an NPD practice. These are: managing uncertainties, knowledge-brokering,managing conflicts of interests, locating knowledge and talent and raising awareness of digital technologies

The Arabidopsis leucine-rich repeat receptor kinase BIR3 negatively regulates BAK1 receptor complex formation and stabilizes BAK1

BAK1 is a co-receptor and positive regulator of multiple ligand-binding leucine-rich-repeat receptor kinases (LRR-RKs) and is involved in brassinosteroid (BR)-dependent growth and development, innate immunity and cell death control. The BAK1-interacting LRR-RKs BIR2 and BIR3 were previously identified by proteomics analyses of in vivo BAK1 complexes. Here we show that BAK1-related pathways such as innate immunity and cell death control are affected by BIR3 in Arabidopsis thaliana. BIR3 also has a strong negative impact on BR signaling. BIR3 directly interacts with the BR receptor BRI1 and other ligand-binding receptors and negatively regulates BR signaling by competitive inhibition of BRI1. BIR3 is released from BAK1 and BRI1 after ligand exposure and directly affects the formation of BAK1 complexes with BRI1 or FLAGELLIN SENSING2. Double mutants of bak1 and bir3 show spontaneous cell death and constitutive activation of defense responses. BAK1 and its closest homolog BKK1 interact with and are stabilized by BIR3, suggesting that bak1 bir3 double mutants mimic the spontaneous cell death phenotype observed in bak1 bkk1 mutants via destabilization of BIR3 target proteins. Our results provide evidence for a negative regulatory mechanism for BAK1 receptor complexes in which BIR3 interacts with BAK1 and inhibits ligand-binding receptors to prevent BAK1 receptor complex formation

Persistent socioeconomic inequalities in cardiovascular risk factors in England over 1994-2008: a time-trend analysis of repeated cross-sectional data

Our aims were to determine the pace of change in cardiovascular risk factors by age, gender and socioeconomic groups from 1994 to 2008, and quantify the magnitude, direction and change in absolute and relative inequalities

Über die Reaktion von Vanillin mit phenolischen Verbindungen

Electron densities at the nucleus of several simple phenols and plant phenols such as catechin and quercetin are calculated by the HMO-method. We found a correlation between the maximum of the electron density at the nucleus and the extinction value of the reaction product with vanillin. With the exception of quercetin an explanation is given by the HMO-calculation. Investigations into the structure of the reaction products have been carried out

Improvements in breast cancer survival over time, related to adjuvant treatment and node status

Background: There has been an increase in the use and effectiveness of adjuvant treatment for operable breast cancer and the aim of this study was to examine whether this has resulted in improved survival for all prognostic groups. Methods: A retrospective study of 1517 patients with invasive breast cancer treated between 1980 and 2002 was carried out. The use of adjuvant treatment was compared between two time periods in patients based on nodal status, and survival was calculated by Kaplane Meier life table analysis. Independent predictors for recurrence-free survival (RFS) were determined by Cox regression analysis. Results: The use of adjuvant therapy increased for all prognostic groups. On multivariate analysis the use of radiotherapy and endocrine therapy was positively associated with RFS which was significant in the second time period. Outcome in node positive patients improved: five-year RFS from 59% to 76%, p < 0.01 and breast cancer specific survival (BCSS) from 70% to 83%, p < 0.01. However, there was no survival improvement in the larger group of node negative patients; BCSS 93% versus 95%, p ¼ 0.99. Within the node negative group, patients with tumours ? 2 cm had an improved RFS from 80% to 88%, p ¼ 0.02. Conclusion: The increased use of adjuvant therapy was associated with an improved outcome in node positive patients. For node negative patients with good prognostic features the evidence of benefit was marginal