AKT-independent PI3-K signaling in cancer - emerging role for SGK3

The phosphoinositide 3-kinase (PI3-K) signaling pathway plays an important role in a wide variety of fundamental cellular processes, largely mediated via protein kinase B/v-akt murine thymoma viral oncogene homolog (PKB/AKT) signaling. Given the crucial role of PI3-K/AKT signaling in regulating processes such as cell growth, proliferation, and survival, it is not surprising that components of this pathway are frequently dysregulated in cancer, making the AKT kinase family members important therapeutic targets. The large number of clinical trials currently evaluating PI3-K pathway inhibitors as a therapeutic strategy further emphasizes this. The serum- and glucocorticoid-inducible protein kinase (SGK) family is made up of three isoforms, SGK1, 2, and 3, that are PI3-K-dependent, serine/threonine kinases, with similar substrate specificity to AKT. Consequently, the SGK family also regulates similar cell processes to the AKT kinases, including cell proliferation and survival. Importantly, there is emerging evidence demonstrating that SGK3 plays a critical role in AKT-independent oncogenic signaling. This review will focus on the role of SGK3 as a key effector of AKT-independent PI3-K oncogenic signaling

Urban planning as an enabler of urban health: Challenges and good practice in England following the 2012 planning and public health reforms

© 2019 The Authors This article synthesises the challenges faced by the English (urban) spatial planning system to become an enabler of urban health and explores some keys features of the evidence base, policy tools and policy implementation issues that urban planners need to be aware of to become health enablers. It draws on good practice identified in an Economic and Social Research Council (ESRC) seminar series involving over 500 academic researchers and practitioners between 2015 and 2017. A number of key recommendations emerged out of the project. First, planning and health agendas must align at the local level. Second, the evidence base of health priorities must be locally relevant. Third, robust tools can support the creation of frameworks for delivering health outcomes through planning. And finally, adequate resources are necessary to develop the capacity of key place-making stakeholders

Tree planning and planting campaigns : a guide for reforesting cities and towns

This guide is written for planners, landscape architects, urban foresters and arborists, elected officials, community tree advocates or anyone who wants to make the case for robust urban canopies, funding forest expansion and implementing strategic tree-planting campaigns. This guide shows how to craft a compelling argument for the urban forest. It also details the data needed to both set a canopy goal and create realistic, proven strategies for engaging both the public and private sector in growing and sustaining the urban forest. Case studies and examples are provided throughout this guide to show that these ideas really do work

Managing active learning processes in large first year physics classes: The advantages of an integrated approach

Turning lectures into interactive, student-led question and answer sessions is known to increase learning, but enabling interaction in a large class seems aninsurmountable task. This can discourage adoption of this new approach – who has time to individualize responses, address questions from over 200 students and encourage active participation in class? An approach adopted by a teaching team in large first-year classes at a research-intensive university appears to provide a means to do so. We describe the implementation of active learning strategies in a large first-year undergraduate physics unit of study, replacing traditional, content-heavy lectures with an integrated approach to question-driven learning. A key feature of our approach is that it facilitates intensive in-class discussions by requiring students to engage in preparatory reading and answer short written quizzes before every class. The lecturer uses software to rapidly analyze the student responses and identify the main issues faced by the students before the start of each class. We report the success of the integration of student preparation with this analysis and feedback framework, and the impact on the in-class discussions. We also address some of the difficulties commonly experienced by staff preparing for active learning classes

Two rare variants that affect the same amino acid in CFTR have distinct responses to ivacaftor

Some residues in the cystic fibrosis transmembrane conductance regulator (CFTR) channel are the site of more than one CFTR variant that cause cystic fibrosis. Here, we investigated the function of S1159F and S1159P, two variants associated with different clinical phenotypes, which affect the same pore-lining residue in transmembrane segment 12 that are both strongly potentiated by ivacaftor when expressed in CFBE41o− bronchial epithelial cells. To study the single-channel behaviour of CFTR, we applied the patch-clamp technique to Chinese hamster ovary cells heterologously expressing CFTR variants incubated at 27°C to enhance channel residence at the plasma membrane. S1159F- and S1159P-CFTR formed Cl− channels activated by cAMP-dependent phosphorylation and gated by ATP that exhibited thermostability at 37°C. Both variants modestly reduced the single-channel conductance of CFTR. By severely attenuating channel gating, S1159F- and S1159P-CFTR reduced the open probability (Po) of wild-type CFTR by ≥75% at ATP (1 mM); S1159F-CFTR caused the greater decrease in Po consistent with its more severe clinical phenotype. Ivacaftor (10–100 nM) doubled the Po of both CFTR variants without restoring Po values to wild-type levels, but concomitantly, ivacaftor decreased current flow through open channels. For S1159F-CFTR, the reduction of current flow was marked at high (supersaturated) ivacaftor concentrations (0.5–1 μM) and voltage-independent, identifying an additional detrimental action of elevated ivacaftor concentrations. In conclusion, S1159F and S1159P are gating variants, which also affect CFTR processing and conduction, but not stability, necessitating the use of combinations of CFTR modulators to optimally restore their channel activity

Leading institutional change through learning and teaching communities

The potential for Scholarship of Teaching and Learning (SoTL) initiatives to influence practice has been an important issue explored throughout the literature since Boyer’s early discussions on scholarship. While it is now generally accepted that individual inquiry and reflection into teaching and learning issues can positively impact one’s practice, the interest in SoTL has shifted from individual scholarship to wider contexts. In recent years, academic developers and leaders have expressed a desire to better understand how SoTL initiatives can be successfully implemented and embedded at the institutional level as a strategy to not only influence individuals’ practice, but contribute to a broader shift in cultural perspectives on teaching and learning. This paper will discuss recent research on an institutional initiative utilising SoTL as a strategy to simultaneously address staff professional development needs and quality enhancement of learning and teaching. The Learning and Teaching Community Grant Initiative was developed to promote/support learning and teaching initiatives, while investigating and resolving specific educational issues of particular importance to the institution. Key aims of the initiative include: • the formation of academic communities focused on enhanced Scholarship of Teaching and Learning (Cox, 2004; Wenger, 2014); • improved educational practice; • the identification and support of emerging scholars at the institution; and • broad impact on institutional value of SoTL activities. In early 2015, three Learning and Teaching Communities were established to enable the University’s academic and professional staff to collaborate on learning and teaching issues. The research focus is on the ‘lived experience’ (VanManen,1990) of participants, using observation, interviews and focus group methodology. The project will conclude with a Most Significant Change (MSC) analysis in which participants will be asked to identify significant change the project made in their lives. They will then share those reflections, and decide as a group on what they count as most significant (Davies & Dart, 2005). This articulation of the process and outcomes to participants provides feedback and builds transformative knowledge, in line with the philosophy of Learning Communities that underpins the initiative (Cox, 2004; Wenger 2014). Data collected is being analysed to provide formative and summative evaluation of the project to determine the implications for future Learning and Teaching Communities as institutional SoTL initiatives. Preliminary findings of the investigation into the impact of this initiative will be shared. Evidence will be reported regarding: • effective practices identified for using a SoTL community model as a professional development strategy; and • indicators of change in the attitudes and behaviors of participants collectively and individually. These findings will build upon previous work about the potential for learning communities. It is expected that the findings will have practical significance for those striving to enhance practice and promote an institutional culture that recognizes and values SoTL (Furco & Moely, 2012; Schwartz & Haynie, 2013). To promote audience engagement, participants will have time to: • reflect on their perspectives in small groups; • share previous experiences with institutional SoTL initiatives (whole group); and • participate in a Q&A session with presenters and other participants

Banking from Leeds, not London: regional strategy and structure at the Yorkshire Bank, 1859–1952

Industrial philanthropist Edward Akroyd created the Yorkshire Penny Savings Bank in 1859. Despite competition from the Post Office Savings Bank after 1861 and a serious reserve problem in 1911, it sustained his overall strategy to become a successful regional bank. Using archival and contemporary sources to build on recent scholarship illustrating how savings banks were integrated into local economies and the complementary roles of philanthropy and paternalism, we analyse an English regional bank's strategy, including an assessment of strategic innovation, ownership changes and management structure. This will demonstrate that the founder's vision continued, even though the 1911 crisis radically altered both strategy and structure