40 research outputs found
Quantitative Peptidomics with Isotopic and Isobaric Tags
No full textIn differential peptidomics, peptide profiles are compared between biological samples and the resulting expression levels are correlated to a phenotype of interest. This, in turn, allows us insight into how peptides may affect the phenotype of interest. In quantitative differential peptidomics, both label-based and label-free techniques are often employed. Label-based techniques have several advantages over label-free methods, primarily that labels allow for various samples to be pooled prior to liquid chromatography-mass spectrometry (LC-MS) analysis, reducing between-run variation. Here, we detail a method for performing quantitative peptidomics using stable amine-binding isotopic and isobaric tags.status: Publishe
Functional neuropeptidomics in invertebrates
No full textNeuropeptides are key messengers in almost all physiological processes. They originate from larger precursors and are extensively processed to become bioactive. Neuropeptidomics aims to comprehensively identify the collection of neuropeptides in an organism, organ, tissue or cell. The neuropeptidome of several invertebrates is thoroughly explored since they are important model organisms (and models for human diseases), disease vectors and pest species. The charting of the neuropeptidome is the first step towards understanding peptidergic signaling. This review will first discuss the latest developments in exploring the neuropeptidome. The physiological roles and modes of action of neuropeptides can be explored in two ways, which are largely orthogonal and therefore complementary. The first way consists of inferring the functions of neuropeptides by a forward approach where neuropeptide profiles are compared under different physiological conditions. Second is the reverse approach were neuropeptide collections are used to screen for receptor-binding. This is followed by localization studies and functional tests. This review will focus on how these different functional screening methods contributed to the field of invertebrate neuropeptidomics and expanded our knowledge of peptidergic signaling. This article is part of a Special Issue entitled: Neuroproteomics: Applications in Neuroscience and Neurology.sponsorship: The authors acknowledge the Research Foundation Flanders (FWO-Vlaanderen, Belgium, G.04371.0N) and the European Research Council (ERC-2013-ADG-340318). Wouter De Haes is funded by the KU Leuven Research Fund. Elien Van Sinay and Liesbet Temmerman are research fellows of the FWO-Vlaanderen, and Giel Detienne is funded by the Agency for Innovation by Science and Technology in Flanders (IWT). (Research Foundation Flanders (FWO-Vlaanderen, Belgium)|G.04371.0N, European Research Council|ERC-2013-ADG-340318, KU Leuven Research Fund, Agency for Innovation by Science and Technology in Flanders (IWT))status: Publishe
Forty years of Leiden environmental science: the history of the Leiden Institute of Environmental Sciences (CML) 1978-2018
No full textForty years of Leiden environmental sciences relates the story of CML, today one of the Faculty of Science’s eight institutes but with its roots in a more or less in dependent group of ex-activists within the university. Back in the day, many of those at the top of the university would probably have had trouble accepting that ‘those upstarts’ would still be around forty years on – not locked away in some cubbyhole with their stencil duplicator, but as a professor, assistant professor or even a dean. Today they are professors emeritus or have retired: Helias Udo de Haes, Wouter de Groot, Gerard Barendse, Gjalt Huppes, Gerard Persoon, Hans de Iongh and Jan Boersema – which doesn’t stop most of them just carrying on working. And a new generation of environmental scientists is now leading CML’s research and teaching: Geert de Snoo, Arnold Tukker, Martina Vijver, Peter van Bodegom, Jeroen Guinée, Ester van der Voet and René Kleijn.Industrial EcologyConservation Biolog
The essence of insect metamorphosis and aging: Electrical rewiring of cells driven by the principles of juvenile hormone-dependent Ca2+ homeostasis
No full textIn holometabolous insects the fall to zero of the titer of Juvenile Hormone ends its still poorly understood "status quo" mode of action in larvae. Concurrently it initiates metamorphosis of which the programmed cell death of all internal tissues that actively secrete proteins, such as the fat body, midgut, salivary glands, prothoracic glands, etc. is the most drastic aspect. These tissues have a very well developed rough endoplasmic reticulum, a known storage site of intracellular Ca(2+). A persistent high [Ca(2+)]i is toxic, lethal and causal to apoptosis. Metamorphosis becomes a logical phenomenon if analyzed from: (1) the causal link between calcium toxicity and apoptosis; (2) the largely overlooked fact that at least some isoforms of Ca(2+)-ATPases have a binding site for farnesol-like endogenous sesquiterpenoids (FRS). The Ca(2+)-ATPase blocker thapsigargin, like JH a sesquiterpenoid derivative, illustrates how absence of JH might work. The Ca(2+)-homeostasis system is concurrently extremely well conserved in evolution and highly variable, enabling tissue-, developmental-, and species specificity. As long as JH succeeds in keeping [Ca(2+)]i low by keeping the Ca(2+)-ATPases pumping, it acts as "the status quo" hormone. When it disappears, its various inhibitory effects are lifted. The electrical wiring system of cells, in particular in the regenerating tissues, is subject to change during metamorphosis. The possibility is discussed that in vertebrates an endogenous farnesol-like sesquiterpenoid, probably farnesol itself, acts as a functional, but hitherto completely overlooked Juvenile anti-aging "Inbrome", a novel concept in signaling.sponsorship: Thanks to the colleagues who provided relevant information concerning the apoptosis-calcium link, in particular to Prof. Sten Orrenius and colleagues for giving permission to use Fig. 3 that they designed. Also thanks to Marijke Christiaens for help with the illustrations. W. De Haes is supported by a Grant from the Fund for Scientific Research-Flanders (G.04371.0N). T. Janssen is postdoctoral researcher supported by the FWO Flanders. (Fund for Scientific Research Flanders|G.04371.0N, FWO Flanders)status: Publishe
Genetische modulatie van gezondheidsduur in het C. elegans model organisme
No full textstatus: Publishe
Metformine induceert levensduurverlenging via mitohormese in C. elegans
No full textAgeing is seen as a progressive loss-of-function over time, generally thought to be due to the intrinsic accumulation of molecular damage. This leads to an increased susceptibility to intrinsic and environmental stressors and ultimately death. Ageing was long thought to be a passive and random process until pioneering studies near the end of the 20th century showed that a single mutation could increase the lifespan of the bacterivorous nematode Caenorhabditis elegans by more than half. This proved that the rate of ageing can be controlled by factors that are encoded in the genome and that ageing is, in other words, a biological process. As biological processes and pathways can be manipulated, this also started the search for compounds that could extend healthy lifespan. Metformin, an anti-glycaemic biguanide drug and the most common treatment of type II diabetes mellitus, has lifespan-extending capabilities both in rodents and nematodes. Several other human diseases, such as cancer and cardiovascular disease are potentially alleviated by metformin treatment as well. This suggests that metformin acts on common pathways involved in a spectrum of ageing-related disorders. Despite its widespread use, its mode of action is largely unknown.Via a quantitative proteomics approach using the model organism C. elegans, we gained molecular understanding of the physiological changes elicited by metformin exposure, including changes in branched-chain amino acid catabolism and cuticle maintenance. We show that metformin extends lifespan through the process of mitohormesis and propose a signalling cascade in which metformin-induced production of reactive oxygen species (ROS) increases overall life expectancy. These results further add to the increasing body of evidence that mild ROS production, while detrimental at higher concentrations, can cause a beneficial adaptive response leading to increased longevity. We further address an important issue in ageing research, wherein so far, the key molecular link that translates the ROS signal into a pro-longevity cue remained elusive. We show that this beneficial signal of the mitohormetic pathway is propagated by the peroxiredoxin PRDX-2. Because of its evolutionary conservation, peroxiredoxin signalling might underlie a general principle of pro-longevity signalling.It was recently shown that neuronal ROS signalling is sufficient to extend lifespan in C. elegans, implying that the longevity-promoting effects of mitohormesis may be propagated by the endocrine system. While the endocrine factors involved are either largely or completely unknown, they are most likely specific neuropeptides. The development of a high-throughput quantitative peptidomics technique for the profiling of these peptides may lead to the identification of these promising mediators of longevity. In this thesis, we described a promising label-based approach for differential peptidomics that may, in time, be used to study the endocrine regulationof ageing. While this work mainly accentuates thepower of differential proteomics, using a more integrated approach combining proteomics, peptidomics, redox proteomics and others may lead to a more comprehensive map of the regulation of C. elegans longevity.status: Publishe
Proposing a life cycle land use impact calculation methodology
No full textThe Life Cycle Assessment (LCA) community is yet to come to a consensus on a methodology to incorporate land use in LCA, still struggling with what exactly should be assessed and which indicators should be used. To solve this problem we start from concepts and models describing how ecosystems function and sustain, in order to understand how land use affects them. Earlier our research group presented a methodology based on the ecosystem exergy concept. This concept as based on the hypothesis that ecosystems develop towards more effective degradation of exergy fluxes passing through the system and is derived from two axioms: the principles of (i) maximum exergy storage and the (ii) maximum exergy dissipation. This concept aiming at the area of protection natural environment is different from conventional exergy analysis in LCA focusing on natural resources. To prevent confusion, the ecosystem exergy concept is further referred to as the MAximum Storage and Dissipation concept (MASD concept). In this paper we present how this concept identifies end-point impacts, mid-point impacts and mid-point indicators. The identified end-point impacts to assess are Ecosystem Structural Quality (ESQ) and Ecosystem Functional Quality (EFQ). In order to quantify these end-point impacts a dynamic multi-indicator set is proposed for quantifying the mid-point impacts on soil fertility, biodiversity and biomass production (quantifying the ESQ) and soil structure, vegetation structure and on-site water balance (quantifying the EFQ). Further we present an impact calculation method suitable for different environmental assessment tools and demonstrate the incorporation of the methodology in LCA
