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HOBOKEN, N.J.--(BUSINESS WIRE)--The Wiley Foundation, part of John Wiley & Sons, Inc. (NYSE: JWa and JWb) today announced the 16th annual Wiley Prize in Biomedical Sciences will be awarded to Joachim Frank, Richard Henderson, and Marin van Heel for pioneering developments in electron microscopy that are transforming structural studies of biological molecules and their complexes. Dr. Joachim Frank is an HHMI investigator, a Professor of Biochemistry and Molecular Biophysics and of Biological Sciences at Columbia University, and Distinguished Professor of the State University of New York at Albany. Dr. Richard Henderson is a scientist at the MRC Laboratory of Molecular Biology in Cambridge, UK. He was Director from 1996 to 2006, and is a fellow of the Royal Society and a Foreign Associate of the US National Academy of Sciences. Dr. Marin van Heel is a visiting Professor at the National Nanotechnology Laboratory – LNNano/CNPEM, Campinas, Brazil. He is an Emeritus Professor at the Institute of Biology Leiden (NeCEN) and the Department of Life Sciences, Imperial College London. “The 2017 Wiley Prize honors scientists who have developed cryo-electron microscopy to be the most important new tool for establishing atomic structures of large molecular complexes," said Dr. Günter Blobel, Chairman of the awards jury for the Wiley Prize. First awarded in 2002, The Wiley Prize in Biomedical Sciences is presented annually to recognize contributions that have opened new fields of research or have advanced concepts in a particular biomedical discipline. Among the many distinguished recipients of the Wiley Prize in Biomedical Sciences, six have gone on to be awarded the Nobel Prize in Physiology or Medicine. “The Wiley Foundation honors leadership and innovation in the development of techniques that greatly advance scientific discovery. The work of the 2017 Wiley Prize recipients Joachim Frank, Richard Henderson, and Marin van Heel truly upholds this mission,” said Deborah E. Wiley, Chair of the Wiley Foundation. “We are pleased to highlight the impact that cryo-electron microscopy has had in advancing knowledge of molecular structure and resulting cellular functions.” This year’s award of $50,000 will be presented to the winners on April 7, 2017 at the Wiley Prize luncheon at The Rockefeller University. The winners will then deliver an honorary lecture as part of The Rockefeller University Lecture Series. This event will be live streamed via the Current Protocols’ Webinar Series and registration is free. Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical, and scholarly journals, combined with our digital learning, assessment and certification solutions help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. Dr. Joachim Frank is an HHMI investigator, a Professor of Biochemistry and Molecular Biophysics and of Biological Sciences at Columbia University, and Distinguished Professor of the State University of New York at Albany. He is a Member of the National Academy of Sciences, and Fellow of the American Academy of Arts and Sciences, the American Association for the Advancement of Science, and the Biophysical Society. In 2014 he received the Franklin Medal in Life Science, bestowed by the Franklin Institute in Philadelphia. Dr. Richard Henderson is a scientist at the MRC Laboratory of Molecular Biology in Cambridge, UK. He was Director from 1996 to 2006, and is a fellow of the Royal Society and a Foreign Associate of the US National Academy of Sciences. Dr. Marin van Heel is a visiting Professor at the National Nanotechnology Laboratory – LNNano/CNPEM, Campinas, Brazil. He is an Emeritus Professor at the Institute of Biology Leiden (NeCEN) and the Department of Life Sciences, Imperial College London. After studying theoretical optics at the University of Groningen, his PhD thesis marked the beginning of a career in methodology development in structural biology by cryo-EM. He received the Ernst Ruska Prize 1987.


Leslie N.R.,Heriot - Watt University | Den Hertog J.,University Utrecht | Den Hertog J.,Institute of Biology Leiden
Cell | Year: 2014

Tumor suppressors block the development of cancer and are often lost during tumor development. Papa et al. show that partial loss of normal PTEN tumor suppressor function can be compounded by additional disruption caused by the expression of inactive mutant PTEN protein. This has significant implications for patients with PTEN gene mutations. © 2014 Elsevier Inc.


Le Ralec A.,University of Rennes 1 | Anselme C.,University of Nice Sophia Antipolis | Outreman Y.,University of Rennes 1 | Poirie M.,University of Nice Sophia Antipolis | And 3 more authors.
Comptes Rendus - Biologies | Year: 2010

Many organisms, including entomopathogenous fungi, predators or parasites, use aphids as ressources. Parasites of aphids are mostly endoparasitoid insects, i.e. insects which lay eggs inside the body of an other insect which will die as a result of their development. In this article, we review the consequences of the numerous pecularities of aphid biology and ecology for their endoparasitoids, notably the Aphidiinae (Hymenoptera: Braconidae). We first examine the various mechanisms used by aphids for defence against these enemies. We then explore the strategies used by aphidiine parasitoids to exploit their aphid hosts. Finally, we consider the responses of both aphids and parasitoids to ecological constraints induced by seasonal cycles and to environmental variations linked to host plants and climate. The fundamental and applied interest of studying these organisms is discussed. © 2010 Académie des sciences.


Jorgensen T.R.,Institute of Biology Leiden | Jorgensen T.R.,Kluyver Center for Genomics of Industrial Fermentation | Jorgensen T.R.,Novo Nordisk AS | Nitsche B.M.,Institute of Biology Leiden | And 7 more authors.
Applied and Environmental Microbiology | Year: 2010

The physiology of filamentous fungi at growth rates approaching zero has been subject to limited study and exploitation. With the aim of uncoupling product formation from growth, we have revisited and improved the retentostat cultivation method for Aspergillus niger. A new retention device was designed allowing reliable and nearly complete cell retention even at high flow rates. Transcriptomic analysis was used to explore the potential for product formation at very low specific growth rates. The carbon- and energy-limited retentostat cultures were highly reproducible. While the specific growth rate approached zero (<0.005 h-1), the growth yield stabilized at a minimum (0.20 g of dry weight per g of maltose). The severe limitation led to asexual differentiation, and the supplied substrate was used for spore formation and secondary metabolism. Three physiologically distinct phases of the retentostat cultures were subjected to genome-wide transcriptomic analysis. The severe substrate limitation and sporulation were clearly reflected in the transcriptome. The transition from vegetative to reproductive growth was characterized by downregulation of genes encoding secreted substrate hydrolases and cell cycle genes and upregulation of many genes encoding secreted small cysteine-rich proteins and secondary metabolism genes. Transcription of known secretory pathway genes suggests that A. niger becomes adapted to secretion of small cysteine-rich proteins. The perspective is that A. niger cultures as they approach a zero growth rate can be used as a cell factory for production of secondary metabolites and cysteine-rich proteins. We propose that the improved retentostat method can be used in fundamental studies of differentiation and is applicable to filamentous fungi in general. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Brattstrom O.,Lund University | Brattstrom O.,Institute of Biology Leiden | AKesson S.,Lund University | Bensch S.,Lund University
Ecological Entomology | Year: 2010

The genetic differentiation in a migratory butterfly, the red admiral (Vanessa atalanta), was investigated to discern patterns of migratory routes used across Europe. AFLP profiles showed significant differences between almost all sampled locations, but there was no clear pattern of isolation-by-distance. Using the software STRUCTURE 2.2, we found two distinct genotype clusters present in different frequencies at all study sites. The frequencies of these genotypic clusters varied significantly between years within the same site. Remarkably few individuals were of mixed ancestry, indicating that some isolating mechanisms are present. Twenty-seven mtDNA haplotypes were identified but they showed no geographic structure, nor were they related to either of the two genotype clusters identified in the AFLP data. Most field observations of migrating red admirals suggest a regular north-south migration pattern in Europe. Our data indicate both long-distance migration and a more variable pattern in orientation, since the composition of the two genotypic clusters shows dramatic variation between sites and years in the northern part of the distribution range. © 2010 The Authors. Journal compilation © 2010 The Royal Entomological Society.


Rolloos M.,Institute of Biology Leiden | Dohmen M.H.C.,Institute of Biology Leiden | Hooykaas P.J.J.,Institute of Biology Leiden | Van der Zaal B.J.,Institute of Biology Leiden
Molecular Microbiology | Year: 2014

Summary: Agrobacterium tumefaciens cells carrying a tumour inducing plasmid (Ti-plasmid) can transfer a defined region of transfer DNA (T-DNA) to plant cells as well as to yeast. This process of Agrobacterium-mediated transformation (AMT) eventually results in the incorporation of the T-DNA in the genomic DNA of the recipient cells. All available evidence indicates that T-strand transfer closely resembles conjugal DNA transfer as found between Gram-negative bacteria. However, where conjugal plasmid DNA transfer starts via relaxase-mediated processing of a single origin of transfer (oriT), the T-DNA is flanked by two imperfect direct border repeats which are both substrates for the Ti-plasmid encoded relaxase VirD2. Yeast was used as a model system to investigate the requirements of the recipient cell for the formation of T-DNA circles after AMT. It was found that, despite the absence of self-homology on the T-DNA, the homologous repair proteins Rad52 and Rad51 are involved in T-DNA circle formation. A model is presented involving the formation of T-DNA concatemers derived from T-strands by a process of strand-transfer catalysed by VirD2. These concatemers are then resolved into T-DNA circles by homologous recombination in the recipient cell. © 2014 John Wiley & Sons Ltd.


de Jong T.J.,Institute of Biology Leiden | van Goeverden S.,Institute of Biology Leiden | Jacobs R.,Institute of Biology Leiden | Rurenga K.,Institute of Biology Leiden | Robbers Y.,Leiden University
Basic and Applied Ecology | Year: 2016

Seeds of cultivars of the crop oil seed rape (Brassica napus) differ widely in their content of glucosinolates (GS) and erucic acid (EA), while seeds of the wild relative . B. rapa have a high content of both. If mice were to distinguish between the seed types this could affect persistence of plant populations.In a choice experiment in two habitats seven seed types were offered to seed predators, mainly mice, and to captured individuals of the wood mouse . Apodemus sylvaticus.Seed predators clearly distinguished between seeds of the two species and between different cultivars of . B. napus. In three experiments the amount of seeds eaten had a high, negative correlation with GS content (rank correlation coefficient -0.81 to -0.91). Correlations with EA were lower (-0.33 to -0.52) and not statistically significant. When offered a choice between two seed types with similar GS content, mice chose those with the lower EA content.Double-zero (low GS and low EA) cultivars of . B. napus suffer heavily from post-dispersal seed predation while cultivars with high GS and/or EA suffer less, making the latter potentially more persistent. We suggest that the consistently high GS and EA content in seeds collected in wild populations of . B. rapa is an adaptation that reduces seed predation. Samen von modernen und alten Kulturrassen der Feldfrucht . Brassica napus unterschieden sich in ihrem Gehalt an Glukosinolaten (GS) und Erucasäure (EA). Samen des Unkrauts . B. rapa haben demgegenüber einen hohen Gehalt von beiden Substanzen. Wenn Mäuse zwischen Samen verschiedener Rassen differenzieren, wird das die Persistenz von Pflanzenpopulationen beeinflussen.Hier wurden in Wahlexperimenten im Freiland (in zwei Habitaten) Samen von sechs Kulturrassen an frei lebenden Prädatoren, vor allem Mäusen, angeboten. Daneben wurden Laborexperimente mit gefangenen Individuen der Waldmaus . Apodemus sylvaticus durchgeführt.Samenprädatoren unterscheiden zwischen Samen von . B. napus und . B. rapa und zwischen Samen von Kulturrassen von . B. napus. In allen Experimenten war der Anteil der Samen, die gefressen wurden, stark negativ korreliert mit dem GS-Gehalt (Rang-Korrelationskoeffizienten -0.81 bis -0.91). Rang-Korrelationen zwischen dem Anteil gefressener Samen mit EA waren niedriger (-0.33 bis -0.52) und nicht signifikant.In den Freilandexperimenten selektierten die Mäuse auf Basis des GS- und EA-Gehalts. Doppel-Null-Kulturrassen (mit geringen GS- und EA-Gehalten) erlitten hohe Samenverluste. Kulturrassen für die Biodieselproduktion wiesen geringe Prädation auf, und das erhöht potentiell die Persistenz dieser Rassen. © 2016 Gesellschaft für Ökologie.


Steenbergen P.J.,Institute of Biology Leiden | Bardine N.,Institute of Biology Leiden
Applied Animal Behaviour Science | Year: 2014

The underlying processes of nociception and pain are, despite the rodent models available, still not fully understood. One of the drawbacks of rodent model systems is the difficulty to screen compound libraries for their influence on nociception, thus slowing down the discovery of novel analgesics for clinical use.Rodent behavioural tasks have been previously adapted for larval zebrafish in our group and in the current manuscript we investigated the possibilities of zebrafish larvae as an additional model system to study nociception and pain and their underlying mechanisms.Zebrafish larvae were exposed to different concentrations of diluted acetic acid, a chemical noxious stimulus, and we measured nociceptive-specific behaviours. Cyclooxygenase-2 (cox-2), a gene known to be involved in nociception, was used as a marker for the activation of nociceptive pathways. Upon exposure to diluted acetic acid, five-day old larval zebrafish showed a concentration dependent increase in locomotor activity. This increase in locomotor activity was accompanied by a stimulus dependent increase in cox-2 mRNA expression, demonstrating that nociceptive pathways were indeed activated. Pre-treatment of the larvae with 0.1. μg/ml buprenorphine before exposure to the noxious stimulus, prevented the behavioural changes induced by the diluted acid. Further, the antinociceptive properties of buprenorphine could be reversed by co-treatment with the μ-receptor antagonist naloxone.In conclusion, our results demonstrate that larval zebrafish as young as five days, show behavioural responses upon exposure to a noxious stimulus. The magnitude of the responses is dependent on the intensity of the stimulus applied and activation of nociceptive pathways was confirmed by altered cox-2 mRNA expression. The analgesic buprenorphine has similar antinociceptive properties in this model as in higher vertebrates and mammals and is able to prevent the behavioural responses induced by the noxious stimulus. We therefore propose zebrafish larvae as a novel model system in nociception and pain related research. © 2013 Elsevier B.V.


Roux O.,CNRS Functional Ecology & Environment Laboratory | Roux O.,French National Center for Scientific Research | Le Lann C.,CNRS Ecosystems, Biodiversity, and Evolution Laboratory | Van Alphen J.J.M.,CNRS Ecosystems, Biodiversity, and Evolution Laboratory | And 2 more authors.
Bulletin of Entomological Research | Year: 2010

Because insects are ectotherms, their physiology, behaviour and fitness are influenced by the ambient temperature. Any changes in environmental temperatures may impact the fitness and life history traits of insects and, thus, affect population dynamics. Here, we experimentally tested the impact of heat shock on the fitness and life history traits of adults of the aphid parasitoid Aphidius avenae and on the later repercussions for their progeny. Our results show that short exposure (1 h) to an elevated temperature (36°C), which is frequently experienced by parasitoids during the summer, resulted in high mortality rates in a parasitoid population and strongly affected the fitness of survivors by drastically reducing reproductive output and triggering a sex-dependent effect on lifespan. Heat stress resulted in greater longevity in surviving females and in shorter longevity in surviving males in comparison with untreated individuals. Viability and the developmental rates of progeny were also affected in a sex-dependent manner. These results underline the ecological importance of the thermal stress response of parasitoid species, not only for survival, but also for maintaining reproductive activities. Copyright © 2010 Cambridge University Press.


PubMed | Institute of Biology Leiden
Type: | Journal: Scientific reports | Year: 2015

Agrobacterium mediated transformation (AMT) has been embraced by biotechnologists as the technology of choice to introduce or alter genetic traits of plants. However, in plants it is virtually impossible to predetermine the integration site of the transferred T-strand unless one is able to generate a double stranded break (DSB) in the DNA at the site of interest. In this study, we used the model organism Saccharomyces cerevisiae to investigate whether the Agrobacterium mediated translocation of site-specific endonucleases via the type IV secretion system (T4SS), concomitantly with T-DNA transfer is possible and whether this can improve the gene targeting efficiency. In addition to that, the effect of different chromatin states on targeted integration, was investigated. It was found that Agrobacterium mediated translocation of the homing endonuclease I-SceI has a positive effect on the integration of T-DNA via the homologous repair (HR) pathway. Furthermore, we obtained evidence that nucleosome removal has a positive effect on I-SceI facilitated T-DNA integration by HR. Reversely; inducing nucleosome formation at the site of integration removes the positive effect of translocated I-SceI on T-DNA integration.

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