UPI Correspondent Helen Thomas

General note: Title and date provided by Bettye Lane.

Proapoptotic BH3-only protein Bid is essential for death receptor-induced apoptosis of pancreatic beta-cells

OBJECTIVE: Apoptosis of pancreatic beta-cells is critical in both diabetes development and failure of islet transplantation. The role in these processes of pro- and antiapoptotic Bcl-2 family proteins, which regulate apoptosis by controlling mitochondrial integrity, remains poorly understood. We investigated the role of the BH3-only protein Bid and the multi-BH domain proapoptotic Bax and Bak, as well as prosurvival Bcl-2, in beta-cell apoptosis. RESEARCH DESIGN AND METHODS: We isolated islets from mice lacking Bid, Bax, or Bak and those overexpressing Bcl-2 and exposed them to Fas ligand, tumor necrosis factor (TNF)-alpha, and proinflammatory cytokines or cytotoxic stimuli that activate the mitochondrial apoptotic pathway (staurosporine, etoposide, gamma-radiation, tunicamycin, and thapsigargin). Nuclear fragmentation was measured by flow cytometry. RESULTS: Development and function of islets were not affected by loss of Bid, and Bid-deficient islets were as susceptible as wild-type islets to cytotoxic stimuli that cause apoptosis via the mitochondrial pathway. In contrast, Bid-deficient islets and those overexpressing antiapoptotic Bcl-2 were protected from Fas ligand-induced apoptosis. Bid-deficient islets were also resistant to apoptosis induced by TNF-alpha plus cycloheximide and were partially resistant to proinflammatory cytokine-induced death. Loss of the multi-BH domain proapoptotic Bax or Bak protected islets partially from death receptor-induced apoptosis. CONCLUSIONS: These results demonstrate that Bid is essential for death receptor-induced apoptosis of islets, similar to its demonstrated role in hepatocytes. This indicates that blocking Bid activity may be useful for protection of islets from immune-mediated attack and possibly also in other pathological states in which beta-cells are destroyed.

Observations of volcanic emissions using satellite remote sensing

Volcanoes pose a threat to the human population at regional and global scales and so efficient monitoring is essential in order to effectively manage and mitigate the risks that they pose. Volcano monitoring from space has been possible for over thirty years and now, more than ever, a suite of instruments exists with the capability to observe emissions of gas and ash from a unique perspective. The goal of this research is to demonstrate the use of a range of satellite-based sensors in order to detect and quantify volcanic sulphur dioxide, and to assess the relative performances of each sensor against one another. Such comparisons are important in order to standardise retrievals and permit better estimations of the global contribution of sulphur dioxide to the atmosphere from volcanoes for climate modelling. In this work, retrievals of volcanic sulphur dioxide from a number of instruments are compared, and the individual performances at quantifying emissions from large, explosive volcanic eruptions are assessed. Retrievals vary widely from sensor to sensor, and often the use of a number of sensors in synergy can provide the most complete picture, rather than just one instrument alone. Volcanic emissions have the ability to result significant economic loses by grounding aircraft due to the high risk associated with ash encountering aircraft. As sulphur dioxide is often easier to measure than ash, it is often used as a proxy. This work examines whether this is a reasonable assumption, using the Icelandic eruption in early 2010 as a case study. Results indicate that although the two species are for the most part collocated, separation can occur under some conditions, meaning that it is essential to accurately measure both species in order to provide effective hazard mitigation. Finally, the usefulness of satellite remote sensing in quantifying the passive degassing from Turrialba, Costa Rica is demonstrated. The increase in activity from 2005 – 2010 can be observed in satellite data prior to the phreatic phase of early 2010, and can therefore potentially provide a useful indication of changing activity at some volcanoes.

XIAP discriminates between type I and type II FAS-induced apoptosis

FAS (also called APO-1 and CD95) and its physiological ligand, FASL, regulate apoptosis of unwanted or dangerous cells, functioning as a guardian against autoimmunity and cancer development. Distinct cell types differ in the mechanisms by which the 'death receptor' FAS triggers their apoptosis. In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including hepatocytes and pancreatic beta-cells, caspase cascade amplification through caspase-8-mediated activation of the pro-apoptotic BCL-2 family member BID (BH3 interacting domain death agonist) is essential. Here we show that loss of XIAP (X-chromosome linked inhibitor of apoptosis protein) function by gene targeting or treatment with a second mitochondria-derived activator of caspases (SMAC, also called DIABLO; direct IAP-binding protein with low pI) mimetic drug in mice rendered hepatocytes and beta-cells independent of BID for FAS-induced apoptosis. These results show that XIAP is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions.

Handbook of courses open to women in British, continental, and Canadian universities /

Mode of access: Internet.

Coleoptera Sanctæ-Helenæ.

Mode of access: Internet.

Burnett Lane : Curatorial Rationale & Scoping Report

Mindful of time line and budget limitations this document, as requested by BBC, acts as an inspirational scope, identifying more ‘live’ opportunities than possible within the current budget. The document's secondary purpose is to identify through consultation, concept development of ideas and budgetary costs associated, a number of projects within this document that can be successfully achieved within the current circumstance. A limited, but successful outcome in this initial phase will help to ensure the continuing invested support of stake-holders, not only in Burnett Lane but in relation to the creative scope of other laneways as identified in the BCC laneway document.

Thomas Young's contribution to visual optics : the Bakerian lecture "On the mechanism of the eye"

Thomas Young (1773-1829) carried out major pioneering work in many different subjects. In 1800 he gave the Bakerian Lecture of the Royal Society on the topic of the “mechanism of the eye”: this was published in the following year (Young, 1801). Young used his own design of optometer to measure refraction and accommodation, and discovered his own astigmatism. He considered the different possible origins of accommodation and confirmed that it was due to change in shape of the lens rather than to change in shape of the cornea or an increase in axial length. However, the paper also dealt with many other aspects of visual and ophthalmic optics, such as biometric parameters, peripheral refraction, longitudinal chromatic aberration, depth-of-focus and instrument myopia. These aspects of the paper have previously received little attention. We now give detailed consideration to these and other less-familiar features of Young’s work and conclude that his studies remain relevant to many of the topics which currently engage visual scientists.

Development of a workplace wellness promotion pilot framework : a case study of the Blue Care Staff Wellness Program

Workplace wellness initiatives are currently unreflective of the multidimensional and holistic nature of the wellness construct. There exists an opportunity for promoters of health to move toward models of workplace wellness promotion that more fully appreciate the interconnected nature of health dimensions and promote them even-handedly. The Blue Care Staff Wellness Program framework was developed in response to a recognised need for consistent and wellness-focused constructs for workplace wellness promotion and dissemination. The framework promotes and supports the individual and organisational wellness of the Blue Care employee population by providing a comprehensive and sustainable employee wellness program. This has been achieved by the adoption of consistent wellness principles to guide the framework conception and theory based development. The use of the framework in a pilot program will provide insight into the frameworks effectiveness in promoting a comprehensive workplace wellness program, and go further to establish the relationship between wellness and productivity in the workplace.

Homodimerization controls the fibroblast growth factor 9 subfamily's receptor binding and heparan sulfate-dependent diffusion in the extracellular matrix

Uncontrolled fibroblast growth factor (FGF) signaling can lead to human diseases, necessitating multiple layers of self-regulatory control mechanisms to keep its activity in check. Herein, we demonstrate that FGF9 and FGF20 ligands undergo a reversible homodimerization, occluding their key receptor binding sites. To test the role of dimerization in ligand autoinhibition, we introduced structure-based mutations into the dimer interfaces of FGF9 and FGF20. The mutations weakened the ability of the ligands to dimerize, effectively increasing the concentrations of monomeric ligands capable of binding and activating their cognate FGF receptor in vitro and in living cells. Interestingly, the monomeric ligands exhibit reduced heparin binding, resulting in their increased radii of heparan sulfate-dependent diffusion and biologic action, as evidenced by the wider dilation area of ex vivo lung cultures in response to implanted mutant FGF9-loaded beads. Hence, our data demonstrate that homodimerization autoregulates FGF9 and FGF20's receptor binding and concentration gradients in the extracellular matrix. Our study is the first to implicate ligand dimerization as an autoregulatory mechanism for growth factor bioactivity and sets the stage for engineering modified FGF9 subfamily ligands, with desired activity for use in both basic and translational research.