Van Loon Research Articles

British Ornithologists' Union Records Committee: 42nd Report (October 2013)

British Ornithologists' Union Records Committee: 42nd Report (October 2013)

HSL and ATGL: the movers and shakers of muscle lipolysis

Intramuscular triglyceride (IMTG) accounts for only a fraction of the total lipid store in the human body. However, given its significant contribution as a substrate for ATP synthesis during exercise, and its proposed role in the development of skeletal muscle insulin resistance, IMTG metabolism has proved to be an area of great scientific interest over the last 20 years. Studies investigating IMTG utilisation during exercise remained equivocal, until methods using immunofluorescence microscopy enabled the muscle fibre type-specific assessment of IMTG content without the interference of extramyocellular adipocytes. Studies using this method convincingly demonstrated that in trained individuals 60–70% of IMTG can be depleted in type I muscle fibres during prolonged moderate-intensity exercise, and can account for up to 50% of total lipid oxidation (van Loon, 2004). Of more clinical relevance were studies highlighting the potential role of intramuscular lipid accumulation in the development of skeletal muscle insulin resistance. This hypothesis has been refined over the last decade, as highly insulin-sensitive, endurance-trained athletes exhibit higher levels of total IMTG and diacylglycerol (DAG) (Amati et al. 2011). It is now hypothesised that the accumulation of ceramides and certain species of membrane-bound DAG are responsible for the inhibition of insulin-mediated glucose uptake.

Abstract B144: Hypoxia imaging with [18F]HX4 PET compared with [18F]FMISO and [18F]FAZA: From preclinical to clinical studies.

Abstract Introduction: Tumor hypoxia is an important prognostic factor in overall survival for chemotherapy and radiotherapy. Quantifying and localizing hypoxia non-invasively is therefore important. At present, hypoxia PET tracers lack high tumor-to-background (TBR) ratios. The nitroimidazole [18F]HX4, has shown promise in pre-clinical (Dubois et al. PNAS 2011) and phase I human setting (van Loon et al. EJNMMI 2010). However, until now no comparative research has been conducted between the latest promising hypoxia tracers in order to define the best marker. In a pre-clinical study [18F]HX4 was compared to the hypoxia tracers [18F]FMISO and [18F]FAZA on 3 endpoints; optimal imaging time point, spatial reproducibility and oxygen dependency. Clinical studies investigated the optimal time point and spatial-temporal stability for [18F]HX4 imaging. Methods: In pre-clinical experiments, WAG/Rij rats bearing rhabdomyosarcoma R1 tumors were injected with 20 ± 4 MBq of [18F]HX4, [18F]FMISO or [18F]FAZA, followed by PET/CT imaging up to 6h post-injection (h p.i.). For each tracer TBR was calculated and reproducibility was investigated by voxel-to-voxel analysis or a DICE similarity coefficient. Oxygen sensitivity was studied by altering the tumoral hypoxia status either by carbogen/nicotinamide treatment or 7% oxygen breathing. In clinical trials, NSCLC (N=15) [NCT01024829, NCT01210378] and HNSCC (N=10) [NCT01347281] patients were injected with 403 ± 53 MBq [18F]HX4 and PET/CT imaging was performed at several time points up to 4h p.i.. Tumor uptake (TBR>1.4), image contrast changes over time, hypoxic fraction (HF) and spatial-temporal stability were evaluated. Results: In pre-clinical setting, [18F]HX4 uptake reached a stabilized and maximal TBR at 3h p.i. (TBR=7.2) which is significantly higher compared to the plateau phase of [18F]FAZA reached at 2h p.i. (TBR=3.9, P<0.05). [18F]FMISO did not reach a plateau. Voxel-to-voxel comparisons and DICE similarity coefficient calculations showed a high short- and long-term spatial reproducibility except for [18F]FAZA, which performed poor on a 48 hour interval. Increasing the hypoxic fraction by 7% oxygen breathing resulted in enhanced mean standardized uptake values for both [18F]HX4 (P<0.01) and [18F]FAZA (P<0.05). Only [18F]FMISO uptake was found to be reversible upon reoxygenation using nicotinamide and carbogen. In patients, a TBR>1.4 was observed in 72% of NSCLC and in 74% of HNSCC target lesions, with average HF of 14 ± 17% and 25 ± 22%, respectively. In the hypoxic lesions, TBR increased up to 4h p.i., providing a better contrast at the latest time-points. [18F]HX4 uptake was stable in time and space for the heterogeneous pattern in NSCLC lesions (2h vs. 4h p.i.: r = 0.77 ± 0.10). Conclusions: Both pre-clinical and clinical studies support [18F]HX4 as a robust hypoxia tracer, with the highest image contrast from 3h p.i. onwards, sensitivity to hypoxia and high reproducibility. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B144. Citation Format: Sarah Peeters, Catharina Zegers, Natasja Lieuwes, Wouter van Elmpt, Frank Hoebers, Hoda Sharifi, Bart Reymen, Michel Öllers, Felix Mottaghy, Jonas Eriksson, Albert Windhorst, Guus van Dongen, Dirk de Ruysscher, Ludwig Dubois, Philippe Lambin. Hypoxia imaging with [18F]HX4 PET compared with [18F]FMISO and [18F]FAZA: From preclinical to clinical studies. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B144.

Degradation of p12 Subunit by CRL4Cdt2 E3 Ligase Inhibits Fork Progression after DNA Damage

After acute DNA damage, the cell arrests S-phase progression by inhibiting origin initiation and fork progression to repair damaged DNA. The intra-S-phase checkpoint kinase Chk1 phosphorylates Cdc25A to target the latter for degradation by CRL1(β-TrCP) and so inhibit origin firing. The mechanism for inhibiting fork progression, however, has not been identified. Here, we show that degradation of p12, the fourth subunit of DNA polymerase δ, is critical for inhibiting fork progression. CRL4(Cdt2) is an E3 ligase that ubiquitinates and degrades p12 after UV treatment. Cells expressing a stable form of p12 exhibit UV-resistant DNA synthesis. DNA fiber assay and alkaline-sucrose gradient assay demonstrate that the impairment of fork progression after DNA damage requires p12 degradation. These results suggest that ubiquitination of p12 through CRL4(Cdt2) and subsequent degradation form one mechanism by which a cell responds to DNA damage to inhibit fork progression.

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van Loon, Mariëtte H. MSc, PhD student; Kok, Ellen M. MSc, PhD student; Kamp, Rachelle J.A. MSc, assistant professor; Carbonell, Katerina Bohle MSc, PhD student; Beckers, Jorrick MSc, PhD student; Frambach, Janneke M. MA, PhD student; de Bruin, Anique B.H. PhD, associate professor Author Information

Visualising Movement: The Seagull

Abstract Where does a seagull spend its day? Overcrowded diagrams don't help you to see it. More cunning designs show it all clearly. Urška Demšar and Emiel van Loon describe how visualising the geography of time and movement supports the study of animal ecology.

The effect of nutrition and exercise in addition to hypoglycemic medications on HbA1C in patients with type 2 diabetes mellitus: a systematic review protocol

The effect of nutrition and exercise in addition to hypoglycemic medications on HbA1C in patients with type 2 diabetes mellitus: a systematic review protocol

Mrs. J.B. Carmichael and the Edmonton Civic Opera Society, 1935-1971

Born in Indiana and trained as a singer, violinist, and conductor in Chicago and New York, Beatrice van Loon travelled to Edmonton, Alberta, in the fall of 1920 as the leader of an all-female ensemble. She married a local dentist and as Mrs. J.B. Carmichael played in the Edmonton Symphony Orchestra and conducted an orchestra at the University of Alberta until 1934. She founded the Edmonton Civic Opera Society in 1935 and worked as its artistic director until her death in 1964. For more than four decades she gave unstintingly of herself to audiences and music students in her adopted city.

The Tawagonshi Tale: Can Linguistic Analysis Prove the Tawagonshi Treaty to be a Forgery?

In 1968 the American physician Lawrence G. van Loon published the text of the so-called Tawagonshi Treaty. This treaty, allegedly drawn up in 1613 between Dutch traders and Iroquois tribal leaders, is by some considered to be the first treaty made between Europeans and Native Americans. Others, however, believe it to be a fake. In this article we try to establish at what date the text was written, using linguistic analysis. Our conclusion is that the anachronisms and anglicisms in the Tawagonshi Treaty demonstrate without doubt that the text was forged in the twentieth century. Although it is plausible that Van Loon was the forger, we have only circumstantial evidence for this but no direct proof.

Transforming creative writing postgraduate and supervisor identities: Ways of becoming professional

In the twenty-first century, research higher degree students in Australia do more than simply research (DIISR 2011a:24, ACER 2011). They might teach or be employed as research assistants or administrators. These jobs prepare RHD (aka HDR) students for transition to the workforce; they inhabit, therefore, multiple identities. Supervisors in the twenty-first century also face the challenge of multiple identities. They act as employers as well as mentors to induct their cohort into a discipline’s professional life. Mentorship, we argue, is not the same as supervision. The mentorship role is especially important in emerging subject areas where the concept of research itself and appropriate methodologies are developing; both supervisor and student might be working as ‘reflective practitioners’ (Schön 1987), each helping the other to refine and theorise practice. This is particularly true of the flourishing but still relatively young discipline of Creative Writing (Brien 2004, Dibble & van Loon 2004, Woods 2007, Harper & Kroll 2008). Some supervisors have always performed a variety of roles, but aspects of the postgraduate experience have been increasingly professionalised, affecting an academic’s access to promotion and offering them another research area – the pedagogy of supervision. This paper explores the nature of these complex relationships focused on the Creative Writing doctoral experience and considers how they impact on the student overall.

Monsoons intensify with peak sunspot activity

Scientists are increasingly pointing toward a strong connection between sunspots and climate, driven by what appears to be a coupled response of the atmosphere all the way from Earth's surface through the stratosphere. Sunspots are dark areas that develop temporarily on the photosphere of the Sun, and when they appear in large numbers, the surface of the Sun cools. The number of sunspots waxes and wanes approximately every 11 years. During the years with the maximum numbers of sunspots, the southeast trade winds over the equatorial region of the Pacific Ocean appear to grow stronger, and the associated major atmospheric systems, like the Hadley and Walker circulations, intensify. These changes in the tropics also influence atmospheric circulation over the northern and southern Pacific as shown in a new study by van Loon and Meehl. There is no observed connection between weather and years with low or average sunspot activity.

Perspectives on the ‘lens of risk’ interview series: Interviews with Joost van Loon and Ortwin Renn

This article is the second of a set which will be published in 2012/2013 in the special issue series Health Care Through the ‘Lens of Risk’. The interviews explore the views of leading social scientists about the study of risk and its societal significance. This particular article shares responses from interviews with two highly influential European social scientists about their approaches to risk. These responses, from Joost van Loon and Ortwin Renn, reflect two somewhat contrasting perspectives towards risk and risk research, although significant areas of common ground and certain compatibilities between their two approaches are also apparent. The complexities and interwovenness of risk considerations, and the challenges these pose to researchers and policy-makers alike, emerge as salient themes.

RETRACTED ARTICLE: Effect of Short Duration Simulated Microgravity on Effectiveness of Local Anesthesia

The journal and publisher would like to inform the readers that this paper has been retracted. The journal had been informed by one of the co-authors, Jack van Loon, that he had noticed after publication that Fig. 1 of the article had been taken from the internet and masked, giving the wrong impression that it is showing the setup used in the studies discussed in the paper. Further investigations by the publisher revealed a significant textual overlap with the paper “Srisurang et al., Journal of Investigative and Clinical Dentistry (2011), 2, 23–28”. While never admitting plagiarism the first author com-

Gentrifying Climate Change: Ecological Modernisation and the Cultural Politics of Definition

Gentrifying Climate Change: Ecological Modernisation and the Cultural Politics of Definition

Spectre of the Past, Vision of the Future – Ritual, Reflexivity and the Hope for Renewal in Yann Arthus-Bertrand’s Climate Change Communication Film "Home"

Spectre of the Past, Vision of the Future – Ritual, Reflexivity and the Hope for Renewal in Yann Arthus-Bertrand’s Climate Change Communication Film "Home"

Cyprian of Carthage. Studies in his life, language, and thought. Edited by Henk Bakker, Paul van Geest and Hans van Loon. (Late Antique History and Religion, 3.) Pp. xx+307. Leuven: Peeters, 2010. €65. 978 90 429 2397 3

Cyprian of Carthage. Studies in his life, language, and thought. Edited by Henk Bakker, Paul van Geest and Hans van Loon. (Late Antique History and Religion, 3.) Pp. xx+307. Leuven: Peeters, 2010. €65. 978 90 429 2397 3

The Effect of Previous Feeding on Water Hyacinth Leaf Acceptability by Three Water Hyacinth Biological Control Agents Measured with a Simple Y-Tube Olfactometer

The odours released by a plant under herbivory pressure are intercepted by other herbivorous insects and can elicit behavioural changes. The relevant information relayed to the herbivorous insect may include the nutritional quality of the plant, the presence of potential competitors and natural enemies (Dicke 2000; Dicke & van Loon 2000). It may be expected that with this information, a herbivorous insect may be attracted to or repelled by a particular host plant, depending on the apparent costs and benefits associated with that plant (Dicke & van Loon 2000).

Co‐infections and the third trophic level

The proverb ‘the enemy of my enemy is my friend’ is axiomatic in community ecology and the study of tri-trophic interactions. This is particularly relevant for studies of plant–herbivore–parasitoid interactions. Parasitoid wasps eavesdrop on plant volatiles emitted after plants are attacked by herbivores (De Moraes et al. 1998). This facilitates host finding by parasitoids, attack by parasitoids reduces population size of herbivore hosts (Rosenheim 1998), and the plants and parasitoids each benefit by the interaction (van Loon et al. 2000). One takes for granted the observation that most plant secondary compounds likely evolved as plant defences against natural enemies, but this was formally proposed as a mechanism only 52 years ago (Frankel 1959). Similarly, plant–insect herbivore–parasitoid interactions are key to understanding plant population dynamics and community ecology, although the conceptual framework for this is also relatively new (Karban et al. 1999). A closer look at life in the tangled bank reveals highly complex ecological interactions and evolutionary outcomes among plants, insect herbivores and the third trophic level. Taking just the case of plant–insect–parasitoid interactions, one finds that most plants are attacked by many herbivore species (co-infections), which are in turn attacked by many parasitoid species, which are attacked by hyperparasitoids, and so on. When examined in detail, such interactions can be driven by complex, unimaginable mechanisms—for example, a phage virus toxin encoded in the genomes of bacterial symbionts of aphids renders hosts resistant to parasitoid wasps (Oliver et al. 2009). Such a complex (and wonderful) ecological and evolutionary milieu might be viewed as an intellectually intractable morass. For example, two herbivorous insect species using a common host plant may compete with or facilitate one another, or may not affect the other’s fitness at all—and—the direction and strength of such interactions are likely to be highly context-dependent. Can we build a robust framework for predicting the direction and strength of plant–herbivore– parasitoid interactions in real ecological communities? Advances in network theory and competition theory are likely to be helpful in understanding how such systems work from an ecological perspective, and potentially how they evolve (Chesson & Kuang 2008; Guimaraes et al. 2011). But are there more fundamental traits of plants that can be leveraged to gain insight into the direction and strength of ecological interactions within these complex communities? In this issue of Functional Ecology, Soler et al. (2012) provide fresh insight into how co-infections robustly modulate plant defence signalling, and then tests whether this influences tri-trophic interactions in a natural ecological community. Widespread signalling cross talk, primarily via the three plant hormones jasmonic acid (JA), salicylic acid (SA) and ethylene (ET), allows plants to coordinate and fine-tune their defences against the diversity of potential natural enemies. Plants deploy distinct, but often overlapping defence strategies against biotrophic microbes, phloem-feeding insects and leaf-chewing herbivores (Stout et al. 2006). Numerous studies have examined the physiological and molecular genetic basis of plant signalling and cross talk, mostly in model plant species (Arabidopsis thaliana, tomato and tobacco). Herbivores and many fungi typically induce the JA pathway and many bacterial and some fungal pathogens the SA pathway, and ET seems to bemodulator of cross talk between the two pathways. While extremely insightful, these studies have led to some typological thinking—that herbivores induce the JA pathway and that bacteria induce the SA pathway. This hazard is apparent when one considers that the causative agent of bacteria speck disease (the Gram-negative bacterium Pseudomonas syringae) in plant leaves will induce either the JA pathway or the SA depending on the presence or absence of single avirulence or virulence genes (Cui et al. 2005). This indicates that it may well be difficult to make predictions about how particular natural enemies induce plant defences, and whether this scales up the trophic cascade to predators. Nonetheless, there are widespread, repeatable and ecologically relevant cross-talk phenotypes present across host plant taxa. For example, the SA pathway and JA pathway are largely mutually antagonistic in plants. How such antagonism affects the their trophic level, as well as interactions among co-infecting natural enemies is relatively unknown, but clearly likely to be extremely important ecologically and evolutionarily (Thaler 1999). Only a handful of elegant studies (e.g. (Rodriguez-Saona et al. 2005)) have examined how plant defence hormone signalling is affected by attack from multiple herbivore species, and how this translates into effects on the herbivores and their parasitoids in the third trophic level. Soler et al. (2012) provide an important step forward by studying co-infection of Brassica oleracea plants by a leaf-chewing herbivore and a phloem-feeding herbivore. The authors cast the effects of *Correspondence author. E-mail: whiteman@email.arizona.edu

A CORNERSTONE IN ARCHITECTURAL HISTORY: THE DEDICATION OF ST. PETER'S ABBEY CHURCH, GHENT, 1629

Previous articleNext article No AccessA CORNERSTONE IN ARCHITECTURAL HISTORY: THE DEDICATION OF ST. PETER'S ABBEY CHURCH, GHENT, 1629Anne-Françoise Morel, and Dagmar GermonprezAnne-Françoise Morel Search for more articles by this author , and Dagmar Germonprez Search for more articles by this author PDFPDF PLUS Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by Source Volume 31, Number 2Winter 2012 Sponsored by the Bard Graduate Center, New York Article DOIhttps://doi.org/10.1086/sou.31.2.23208931 Views: 9Total views on this site Citations: 1Citations are reported from Crossref © 2012 Ars Brevis Foundation Inc.PDF download Crossref reports the following articles citing this article:Maarten Delbeke Religious Architecture and the Image in the Southern Netherlands after the Beeldenstorm : Shrines for Miracle-Working Statues of the Virgin Mary, (Mar 2017): 1–33.https://doi.org/10.1002/9781118887226.wbcha016

A step towards underpinning the molecular signalling events regulating muscle protein loss in critically ill patients

A step towards underpinning the molecular signalling events regulating muscle protein loss in critically ill patients