De Loof Research Articles

MP55-12 VALIDATION OF THE MODIFIED BOSNIAK CLASSIFICATION SYSTEM TO RISK STRATIFY PEDIATRIC CYSTIC RENAL MASSES: AN INTERNATIONAL, MULTI-SITE STUDY FROM THE PEDIATRIC UROLOGIC ONCOLOGY WORKING GROUP OF THE SOCIETIES FOR PEDIATRIC UROLOGY

You have accessJournal of UrologyPediatric Urology V (MP55)1 Sep 2021MP55-12 VALIDATION OF THE MODIFIED BOSNIAK CLASSIFICATION SYSTEM TO RISK STRATIFY PEDIATRIC CYSTIC RENAL MASSES: AN INTERNATIONAL, MULTI-SITE STUDY FROM THE PEDIATRIC UROLOGIC ONCOLOGY WORKING GROUP OF THE SOCIETIES FOR PEDIATRIC UROLOGY Leslie Peard, Patricio Gargollo, Campbell Grant, Andrew Strine, Manon de Loof, Celine Sinatti, Anne-Francoise Spinoit, Piet Hoebeke, Nicholas Cost, Alexandra Rehfuss, Seth Alpert, and Amanda Saltzman Leslie PeardLeslie Peard More articles by this author , Patricio GargolloPatricio Gargollo More articles by this author , Campbell GrantCampbell Grant More articles by this author , Andrew StrineAndrew Strine More articles by this author , Manon de LoofManon de Loof More articles by this author , Celine SinattiCeline Sinatti More articles by this author , Anne-Francoise SpinoitAnne-Francoise Spinoit More articles by this author , Piet HoebekePiet Hoebeke More articles by this author , Nicholas CostNicholas Cost More articles by this author , Alexandra RehfussAlexandra Rehfuss More articles by this author , Seth AlpertSeth Alpert More articles by this author , and Amanda SaltzmanAmanda Saltzman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002085.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Pediatric cystic renal lesions are challenging to manage as little is known about their natural course. A modified Bosniak classification system has been proposed for risk stratification, but literature validating this system remains limited. This study’s objective was to determine if the modified Bosniak classification system correlates with pathologic diagnoses. METHODS: Patients treated for cystic renal masses between 2000 and 2019 from five institutions with available imaging and pathology were identified. Clinical characteristics and pathology were obtained retrospectively. Characteristics from the most recent ultrasound (US), computed tomogram (CT), and/or magnetic resonance films (MRI) were recorded. Reviewers assigned a modified Bosniak classification to each scan. Modified Bosniak scores 1/2 were considered low-risk and 3/4 high-risk. These groups were compared with pathology (benign, intermediate, malignant). Agreement between imaging modalities was also explored. RESULTS: 99 patients were identified. Table 1 summarizes the relationship between modified Bosniak class and pathology. Malignant and intermediate pathologies were classified as high-risk on imaging with a sensitivity of 84%, specificity of 81%, positive predictive value of 85.7%. There was substantial agreement between US/CT (n=55; κ=0.66) and moderate agreement between US/MRI (n=20; κ=0.52) and CT/MRI (n=13; κ=0.47). CONCLUSIONS: Pediatric cystic renal lesions assigned modified Bosniak class 1/2 are mostly benign, whereas class 3/4 lesions are likely intermediate or malignant pathology. However, due to a significant misclassification rate, 16% of malignant lesions would be missed if observed based on the modified Bosniak system alone. Therefore, other clinical characteristics remain important for operative decision-making. There is substantial agreement between US and CT when evaluating pediatric cystic renal lesions. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e963-e963 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Leslie Peard More articles by this author Patricio Gargollo More articles by this author Campbell Grant More articles by this author Andrew Strine More articles by this author Manon de Loof More articles by this author Celine Sinatti More articles by this author Anne-Francoise Spinoit More articles by this author Piet Hoebeke More articles by this author Nicholas Cost More articles by this author Alexandra Rehfuss More articles by this author Seth Alpert More articles by this author Amanda Saltzman More articles by this author Expand All Advertisement Loading ...

GW182 Controls Drosophila Circadian Behavior and PDF-Receptor Signaling

The neuropeptide PDF is crucial for Drosophila circadian behavior: it keeps circadian neurons synchronized. Here, we identify GW182 as a key regulator of PDF signaling. Indeed, GW182 downregulation results in phenotypes similar to those of Pdf and Pdf-receptor (Pdfr) mutants. gw182 genetically interacts with Pdfr and cAMP signaling, which is essential for PDFR function. GW182 mediates miRNA-dependent gene silencing through its interaction with AGO1. Consistently, GW182's AGO1 interaction domain is required for GW182's circadian function. Moreover, our results indicate that GW182 modulates PDFR signaling by silencing the expression of the cAMP phosphodiesterase DUNCE. Importantly, this repression is under photic control, and GW182 activity level--which is limiting in circadian neurons--influences the responses of the circadian neural network to light. We propose that GW182's gene silencing activity functions as a rheostat for PDFR signaling and thus profoundly impacts the circadian neural network and its response to environmental inputs.

Specific Activation of the G Protein-coupled Receptor BNGR-A21 by the Neuropeptide Corazonin from the Silkworm, Bombyx mori, Dually Couples to the Gq and Gs Signaling Cascades

Corazonin, an undecapeptide neurohormone sharing a highly conserved amino acid sequence across Insecta, plays different physiological roles in the regulation of heart contraction rates, silk spinning rates, the induction of dark color and morphometric phase changes, and ecdysis. Corazonin receptors have been identified in Drosophila melanogaster, Manduca sexta, and Musca domestica. However, detailed information on the signaling and major physiological functions of corazonin and its receptor is largely unknown. In the current study, using both the mammalian cell line HEK293 and insect cell lines BmN and Sf21, we paired the Bombyx corazonin neuropeptide as a specific endogenous ligand for the Bombyx neuropeptide G protein-coupled receptor A21 (BNGR-A21), and we therefore designated this receptor as BmCrzR. Further characterization indicated that synthetic BmCrz demonstrated a high affinity for and activated BmCrzR, resulting in intracellular cAMP accumulation, Ca(2+) mobilization, and ERK1/2 phosphorylation via the Gq- and Gs-coupled signaling pathways. The direct interaction of BmCrzR with BmCrz was confirmed by a rhodamine-labeled BmCrz peptide. Moreover, experiments with double-stranded RNA and synthetic peptide injection suggested a possible role of BmCrz/BmCrzR in the regulation of larval growth and spinning rate. Our present results provide the first in-depth information on BmCrzR-mediated signaling for further elucidation of the BmCrz/BmCrzR system in the regulation of fundamental physiological processes.

Harnessing a Physiologic Mechanism for siRNA Delivery With Mimetic Lipoprotein Particles

Therapeutics based on RNA interference (RNAi) have emerged as a potential new class of drugs for treating human disease by silencing the target messenger RNA (mRNA), thereby reducing levels of the corresponding pathogenic protein. The major challenge for RNAi therapeutics is the development of safe delivery vehicles for small interfering RNAs (siRNAs). We previously showed that cholesterol-conjugated siRNAs (chol-siRNA) associate with plasma lipoprotein particles and distribute primarily to the liver after systemic administration to mice. We further demonstrated enhancement of silencing by administration of chol-siRNA pre-associated with isolated high-density lipoprotein (HDL) or low-density lipoprotein (LDL). In this study, we investigated mimetic lipoprotein particle prepared from recombinant apolipoprotein A1 (apoA) and apolipoprotein E3 (apoE) as a delivery vehicle for chol-siRNAs. We show that apoE-containing particle (E-lip) is highly effective in functional delivery of chol-siRNA to mouse liver. E-lip delivery was found to be considerably more potent than apoA-containing particle (A-lip). Furthermore, E-lip–mediated delivery was not significantly affected by high endogenous levels of plasma LDL. These results demonstrate that E-lip has substantial potential as delivery vehicles for lipophilic conjugates of siRNAs.

Remodeling of Lipid Vesicles into Cylindrical Micelles by α-Synuclein in an Extended α-Helical Conformation

α-Synuclein (αS) is a protein with multiple conformations and interactions. Natively unfolded in solution, αS accumulates as amyloid in neurological tissue in Parkinson disease and interacts with membranes under both physiological and pathological conditions. Here, we used cryoelectron microscopy in conjunction with electron paramagnetic resonance (EPR) and other techniques to characterize the ability of αS to remodel vesicles. At molar ratios of 1:5 to 1:40 for protein/lipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol), large spherical vesicles are converted into cylindrical micelles ~50 Å in diameter. Other lipids of the same charge (negative) exhibit generally similar behavior, although bilayer tubes of 150-500 Å in width are also produced, depending on the lipid acyl chains. At higher protein/lipid ratios, discoid particles, 70-100 Å across, are formed. EPR data show that, on cylindrical micelles, αS adopts an extended amphipathic α-helical conformation, with its long axis aligned with the tube axis. The observed geometrical relationship between αS and the micelle suggests that the wedging of its long α-helix into the outer leaflet of a membrane may cause curvature and an anisotropic partition of lipids, leading to tube formation.

Structure of Apolipoprotein A-I N Terminus on Nascent High Density Lipoproteins

Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoproteins (HDL) and a critical element of cholesterol metabolism. To better elucidate the role of the apoA-I structure-function in cholesterol metabolism, the conformation of the apoA-I N terminus (residues 6-98) on nascent HDL was examined by electron paramagnetic resonance (EPR) spectroscopic analysis. A series of 93 apoA-I variants bearing single nitroxide spin label at positions 6-98 was reconstituted onto 9.6-nm HDL particles (rHDL). These particles were subjected to EPR spectral analysis, measuring regional flexibility and side chain solvent accessibility. Secondary structure was elucidated from side-chain mobility and molecular accessibility, wherein two major α-helical domains were localized to residues 6-34 and 50-98. We identified an unstructured segment (residues 35-39) and a β-strand (residues 40-49) between the two helices. Residues 14, 19, 34, 37, 41, and 58 were examined by EPR on 7.8, 8.4, and 9.6 nm rHDL to assess the effect of particle size on the N-terminal structure. Residues 14, 19, and 58 showed no significant rHDL size-dependent spectral or accessibility differences, whereas residues 34, 37, and 41 displayed moderate spectral changes along with substantial rHDL size-dependent differences in molecular accessibility. We have elucidated the secondary structure of the N-terminal domain of apoA-I on 9.6 nm rHDL (residues 6-98) and identified residues in this region that are affected by particle size. We conclude that the inter-helical segment (residues 35-49) plays a role in the adaptation of apoA-I to the particle size of HDL.

2D-NMR reveals different populations of exposed lysine residues in the apoB-100 protein of electronegative and electropositive fractions of LDL particles

Several potentially atherogenic LDL subfractions present low affinity for the LDL receptor, which result in impaired plasma clearance. Electronegative LDL [LDL(-)] is one of these minor subfractions and the molecular basis for its reduced receptor affinity is not well understood. In the present study, high-resolution 2D-NMR spectroscopy has been employed to characterize the surface-exposed lysine residues of the apolipoprotein (apo)B-100 protein in both LDL(-) and LDL(+) subfractions. LDL(+) showed two populations of lysine residues, similar to those previously described in total LDL. "Normal" Lys have a pk(a) of 10.4 whereas "active" Lys have a pk(a) of 8.8 and have been suggested to be involved in receptor binding. In contrast to LDL(+), the LDL(-) subfraction presented a third type of Lys, named as "intermediate" Lys, with a different microenvironment and higher basicity (pk(a) 10.7). These intermediate Lys cannot be reliably identified by 1D-NMR. Because the abundance of normal Lys is similar in LDL(+) and LDL(-), the intermediate Lys in the apoB-100 molecule of LDL(-) should come from a group of active Lys in LDL(+) particles that have a less basic microenvironment in the LDL(-) particle. These differences between LDL(+) and LDL(-) are indicative of a distinct conformation of apoB-100 that could be related to loss of affinity of LDL(-) for the LDL receptor.

Allatotropin-related peptide in cockroaches: Identification via mass spectrometric analysis of single identified neurons

The first insect allatotropin-related peptide (ATRP) was isolated from head extracts of the adult sphinx moth Manduca sexta [Kataoka H, Toschi A, Li JP, Carney RL, Schooley DA, Kramer SJ. Identification of an allatotropin from adult Manduca sexta. Science 1989;243:1481–3.]. Meanwhile ATRPs are known from different holometabolous insects but only a single ATRP could be identified from hemimetabolous insects [Paemen L, Tips A, Schoofs L, Proost P, Van Damme J, De Loof A. Lom-AG-myotropin: a novel myotropic peptide from the male accessory glands of Locusta migratoria. Peptides 1991;12:7–10.]. This means that the extensive analysis of neuropeptides from Leucophaea maderae and Periplaneta americana, which led to the discovery of many novel insect neuropeptides, did not result in the detection of any ATRP. In this study, we used another approach to find a cockroach ATRP by first identifying Manse-AT immunoreactive neurons in the terminal ganglion that can be stained by retrograde labeling and are suitable for dissection and subsequent mass spectrometric analysis. The peptidomic analysis of these putative ATRP neurons paved the way for the identification of the first cockroach ATRP. MALDI-TOF/TOF tandem mass spectrometry revealed a sequence identity with Locmi-AG-MT-1 which classifies this ATRP as a highly conserved neuropeptide. A mass spectrometric screening of the nervous system allowed the detection of ATRP-ion signals in different parts of the CNS of P. americana as well as L. maderae. The data obtained in this study will be incorporated in a map of peptidergic neurons from the CNS of the American cockroach, P. americana.

Charged Amino Acid Residues 997–1000 of Human Apolipoprotein B100 Are Critical for the Initiation of Lipoprotein Assembly and the Formation of a Stable Lipidated Primordial Particle in McA-RH7777 Cells

We previously demonstrated that a portion, or perhaps all, of the residues between 931 and 1000 of apolipoprotein (apo) B100 are required for the initiation of apoB-containing particle assembly. Based on our structural model of the first 1000 residues of apoB (designated as apoB:1000), we hypothesized that this domain folds into a three-sided lipovitellin-like "lipid pocket" via a hairpin-bridge mechanism. We proposed that salt bridges are formed between four tandem charged residues 717-720 in the turn of the hairpin bridge and four tandem complementary residues 997-1000 located at the C-terminal end of the model. To identify the specific motif within residues 931 and 1000 that is critical for apoB particle assembly, apoB:956 and apoB:986 were produced. To test the hairpin-bridge hypothesis, the following mutations were made: 1) residues 997-1000 deletion (apoB:996), 2) residues 717-720 deletion (apoB:1000Delta717-720), and 3) substitution of charged residues 997-1000 with alanines (apoB:996 + 4Ala). Characterization of particles secreted by stable transformants of McA-RH7777 cells demonstrated the following. 1) ApoB:956 did not form stable particles and was secreted as large lipid-rich aggregates. 2) ApoB:986 formed both a lipidated particle that was denser than HDL(3) and large lipid-rich aggregates. 3) Compared with wild-type apoB:1000, apoB:1000Delta717-720 displayed the following: (i) significantly diminished capacity to form intact lipidated particles and (ii) increased propensity to form large lipid-rich aggregates. 4) In striking contrast to wild-type apoB:1000, (i) apoB:996 and apoB:996 + 4Ala were highly susceptible to intracellular degradation, (ii) only a small proportion of the secreted proteins formed stable HDL(3)-like lipoproteins, and (iii) a majority of the secreted proteins formed large lipid-rich aggregates. We conclude that the first 1000 amino acid residues of human apoB100 are required for the initiation of nascent apoB-containing lipoprotein assembly, and residues 717-720 and 997-1000 play key roles in this process, perhaps via a hairpin-bridge mechanism.

Functional Characterization of Three G Protein-coupled Receptors for Pigment Dispersing Factors in Caenorhabditis elegans

Here, we report the identification, cloning, and functional characterization of three Caenorhabditis elegans G protein-coupled pigment dispersing factor (PDF) receptors, which we designated as Ce_PDFR-1a, -b, and -c. They represent three splice isoforms of the same gene (C13B9.4), which share a high degree of similarity with the Drosophila PDF receptor and are distantly related to the mammalian vasoactive intestinal peptide receptors (VPAC2) and calcitonin receptors. In a reverse pharmacological screen, three bioactive C. elegans neuropeptides, which were recently identified as the Drosophila PDF orthologues, were able to activate these receptors in a dose-dependent manner with nanomolar potency (isoforms a and b). Integrated green fluorescent protein reporter constructs reveal the expression of these PDF receptors in all body wall muscle cells and many head and tail neurons involved in the integration of environmental stimuli and the control of locomotion. Using a custom data analysis system, we demonstrate the involvement of this newly discovered neuropeptide signaling system in the regulation of locomotor behavior. Overexpression of PDF-2 phenocopies the locomotor defects of a PDF-1 null mutant, suggesting that they elicit opposite effects on locomotion through the identified PDF receptors. Our findings strengthen the hypothesis that the PDF signaling system, which imposes the circadian clock rhythm on behavior in Drosophila, has been functionally conserved throughout the protostomian evolutionary lineage.

Widespread Receptivity to Neuropeptide PDF throughout the Neuronal Circadian Clock Network of Drosophila Revealed by Real-Time Cyclic AMP Imaging

The neuropeptide PDF is released by sixteen clock neurons in Drosophila and helps maintain circadian activity rhythms by coordinating a network of approximately 150 neuronal clocks. Whether PDF acts directly on elements of this neural network remains unknown. We address this question by adapting Epac1-camps, a genetically encoded cAMP FRET sensor, for use in the living brain. We find that a subset of the PDF-expressing neurons respond to PDF with long-lasting cAMP increases and confirm that such responses require the PDF receptor. In contrast, an unrelated Drosophila neuropeptide, DH31, stimulates large cAMP increases in all PDF-expressing clock neurons. Thus, the network of approximately 150 clock neurons displays widespread, though not uniform, PDF receptivity. This work introduces a sensitive means of measuring cAMP changes in a living brain with subcellular resolution. Specifically, it experimentally confirms the longstanding hypothesis that PDF is a direct modulator of most neurons in the Drosophila clock network.

Electron Paramagnetic Resonance Spectroscopy of Site-directed Spin Labels Reveals the Structural Heterogeneity in the N-terminal Domain of ApoA-I in Solution

Apolipoprotein A-I (apoA-I) is the major protein constituent of high density lipoprotein (HDL) and plays a central role in phospholipid and cholesterol metabolism. This 243-residue long protein is remarkably flexible and assumes numerous lipid-dependent conformations. Consequently, definitive structural determination of lipid-free apoA-I in solution has been difficult. Using electron paramagnetic spectroscopy of site-directed spin labels in the N-terminal domain of apoA-I (residues 1-98) we have mapped a mixture of secondary structural elements, the composition of which is consistent with findings from other in-solution methods. Based on side chain mobility and their accessibility to polar and non-polar spin relaxers, the precise location of secondary elements for amino acids 14-98 was determined for both lipid-free and lipid-bound apoA-I. Based on intermolecular dipolar coupling at positions 26, 44, and 64, these secondary structural elements were arranged into a tertiary fold to generate a structural model for lipid-free apoA-I in solution.

Structural and Functional Variations in Human Apolipoprotein E3 and E4

There are three major apolipoprotein E (apoE) isoforms. Although APOE-epsilon3 is considered a longevity gene, APOE-epsilon4 is a dual risk factor to atherosclerosis and Alzheimer disease. We have expressed full-length and N- and C-terminal truncated apoE3 and apoE4 tailored to eliminate helix and domain interactions to unveil structural and functional disturbances. The N-terminal truncated apoE4-(72-299) and C-terminal truncated apoE4-(1-231) showed more complicated or aggregated species than those of the corresponding apoE3 counterparts. This isoformic structural variation did not exist in the presence of dihexanoylphosphatidylcholine. The C-terminal truncated apoE-(1-191) and apoE-(1-231) proteins greatly lost lipid binding ability as illustrated by the dimyristoylphosphatidylcholine turbidity clearance. The low density lipoprotein (LDL) receptor binding ability, determined by a competition binding assay of 3H-LDL to the LDL receptor of HepG2 cells, showed that apoE4 proteins with N-terminal (apoE4-(72-299)), C-terminal (apoE4-(1-231)), or complete C-terminal truncation (apoE4-(1-191)) maintained greater receptor binding abilities than their apoE3 counterparts. The cholesterol-lowering abilities of apoE3-(72-299) and apoE3-(1-231) in apoE-deficient mice were decreased significantly. The structural preference of apoE4 to remain functional in solution may explain the enhanced opportunity of apoE4 isoform to display its pathophysiologic functions in atherosclerosis and Alzheimer disease.

Functional Screening of Serine Protease Inhibitors in the Medical Leech Hirudo medicinalis Monitored by Intensity Fading MALDI-TOF MS

The blood-feeding invertebrates are a rich biological source of drugs and lead compounds to treat cardiovascular diseases because they have evolved highly efficient mechanisms to feed on their hosts by blocking blood coagulation. In this work, we focused our attention on the leech Hirudo medicinalis. We performed, by "intensity fading" MALDI-TOF mass spectrometry, a comprehensive detection and functional analysis of pre-existent peptides and small proteins with the capability of binding to trypsin-like proteases related to blood coagulation. Combining "intensity fading MS" and off-line LC prefractionation allowed us to detect more than 75 molecules present in the leech extract that interact specifically with a trypsin-like protease over a sample profile of nearly 2,000 different peptides/proteins in the 2-20-kDa range. Moreover we resolved 232 individual components from the complex mixture, 13 of which have high sequence homology with previously described serine protease inhibitors. Our findings indicate that such extracts are much more complex than expected. Additionally, intensity fading MS, when complemented with LC separation strategies, seems to be a useful tool to investigate complex biological samples, establishing a new bridge between profiling, functional peptidomics, and subsequent drug discovery.

Osmotically Induced Membrane Tension Modulates Membrane Permeabilization by Class L Amphipathic Helical Peptides: Nucleation Model of Defect Formation

The mechanism of action of lytic peptides on membranes is widely studied and is important in view of potential medical applications. Previously (I. V. Polozov, A. I. Polozova, E. M. Tytler, G. M. Anantharamaiah, J. P. Segrest, G. A. Woolley, and R. M. Epand, 1997, Biochemistry, 36:9237–9245) we analyzed the mechanism of membrane permeabilization by 18L, the archetype lytic peptide featuring the class L amphipathic α-helix, according to the classification of Segrest et al. (J. P. Segrest, G. de Loof, J. G. Dohlman, C. G. Brouillette, and G. M. Anantharamaiah, 1990, Proteins, 8:103–117). We concluded that the 18L peptide destabilizes membranes, leading to a transient formation of large defects that result in contents leakage and, in the presence of bilayer-bilayer contact, could lead to vesicle fusion. Here we report that this defect formation is strongly enhanced by the membrane tension induced by osmotic swelling of vesicles. Even below standard leakage-inducing peptide/lipid ratios, membrane resistance to osmotic tension drops from hundreds to tens of milliosmoles. The actual decrease is dependent on the peptide/lipid ratio and on the type of lipid. We propose that under membrane tension a peptidic pore serves as a nucleation site for the transient formation of a lipidic pore. The tension is released upon pore expansion with inclusion of more peptides and lipids into the pore lining. This tension modulation of leakage was observed for other class L peptides (mastoparan, K18L) and thus may be of general applicability for the action of membrane active lytic peptides.

Neuropeptides in insect development and reproduction.

Archives of Insect Biochemistry and PhysiologyVolume 47, Issue 3 p. 127-128 IntroductionFree Access Neuropeptides in insect development and reproduction Arnold De Loof, Arnold De Loof Catholic University Leuven, BelguimSearch for more papers by this authorKlaus H. Hoffmann, Klaus H. Hoffmann University of Bayreuth, GermanySearch for more papers by this author Arnold De Loof, Arnold De Loof Catholic University Leuven, BelguimSearch for more papers by this authorKlaus H. Hoffmann, Klaus H. Hoffmann University of Bayreuth, GermanySearch for more papers by this author First published: 15 June 2001 https://doi.org/10.1002/arch.1043Citations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. LITERATURE CITED Adams, et al. 2000. The genome sequence of Drosophila melanogaster. Science 287: 2185– 2195. De Loof A, Schoofs L. 1990. Homologies between the amino acid sequences of some vertebrate peptide hormones and peptides isolated from invertebrate sources. Comp Biochem Physiol 95B: 459– 468. Gäde G, Hoffmann KH, Spring JH. 1997. Hormonal regulation in insects: facts, gaps and future directions. Physiol Rev 77: 963– 1032. Hoffmann KH, Meyering-Vos M, Lorenz MW. 1999. Allatostatins and allatotropins: is the regulation of corpora allata activity their primary function? Eur J Entomol 96 255– 266. Schoofs L, Vanden Broeck J, De Loof A. 1993. The myotropic peptides of Locusta migratoria: stuctures, distribution, functions and receptors. Insect Biochem Mol Biol 23: 859– 881. Starratt AN, Brown BE. 1975. Structure of the pentatpeptide proctolin, a proposed neurotransmitter in insects. Life Sci 17: 1253– 1256. Stone JV, Mordue W, Batley KE, Morris HR. 1976. Structure of locus adipokinetic hormone, a neurohormone that regulates lipid utilization during flight. Nature 263: 207– 211. Tawfik AI, Tanaka S, De Loof A, Schoofs L, Baggerman G, Waelkens E, Derua R, Milner Y, Yerushalmi Y, Pener P. 1999. Identification of the gregarization-associated dark-pigmentotropin in locusts through an albino mutant. Proc Natl Acad Sci USA 96: 7083– 7087. Vanden Broeck J. 1996. G protein-coupled receptors in insect cells. Int Rev Cytol 164: 189– 269. Citing Literature Volume47, Issue3Special Issue: Neuropeptides in Insect Development and Reproduction, Part IJuly 2001Pages 127-128 ReferencesRelatedInformation

L to d Amino Acid Isomerization in a Peptide Hormone Is a Late Post-translational Event Occurring in Specialized Neurosecretory Cells

Modification of the chirality of a single amino acid residue within a peptide chain appears to be novel additional mechanism leading to structural and functional diversification of eukaryotic bioactive peptides. This phenomenon has been studied at the cellular level in a neuroendocrine organ which elaborates a mixture of diastereoisomers of a 72-residue neuropeptide, crustacean hyperglycemic hormone. For the first time, amino acid isomerization has been shown to occur in the perikarya of fully specialized neurosecretory cells, as a late step of the maturation of the hyperglycemic hormone precursor and after propeptide cleavage. The specificity and efficiency of this phenomenon indicates the existence of a new enzyme family involved in the biogenesis of peptide hormones.

A Key Point Mutation (V156E) Affects the Structure and Functions of Human Apolipoprotein A-I

A Key Point Mutation (V156E) Affects the Structure and Functions of Human Apolipoprotein A-I

Compounds from Immature Insects Toxic to Adults: Identification and Possible Relation to Metamorphosis

Annals of the New York Academy of SciencesVolume 839, Issue 1 p. 571-573 Compounds from Immature Insects Toxic to Adults: Identification and Possible Relation to Metamorphosis S.-J. CHIOU, S.-J. CHIOU Department of Biology, University of Leuven, Naamsestraat 59, B-3000 Leuven, BelgiumSearch for more papers by this authorP. VERHAERT, P. VERHAERT Department of Biology, University of Leuven, Naamsestraat 59, B-3000 Leuven, BelgiumSearch for more papers by this authorA. DE LOOF, A. DE LOOF Department of Biology, University of Leuven, Naamsestraat 59, B-3000 Leuven, BelgiumSearch for more papers by this authorJ.VANDEN BROECK, J.VANDEN BROECK Department of Biology, University of Leuven, Naamsestraat 59, B-3000 Leuven, BelgiumSearch for more papers by this authorL. SCHOOFS, L. SCHOOFS Department of Biology, University of Leuven, Naamsestraat 59, B-3000 Leuven, BelgiumSearch for more papers by this authorM. CLAEYS, M. CLAEYS Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, BelgiumSearch for more papers by this authorJ.-M. PASTEELS, J.-M. PASTEELS Departments of Biochemistry and Biology, University of Brussels, Brussels, BelgiumSearch for more papers by this authorD. DALOZE, D. DALOZE Departments of Biochemistry and Biology, University of Brussels, Brussels, BelgiumSearch for more papers by this author S.-J. CHIOU, S.-J. CHIOU Department of Biology, University of Leuven, Naamsestraat 59, B-3000 Leuven, BelgiumSearch for more papers by this authorP. VERHAERT, P. VERHAERT Department of Biology, University of Leuven, Naamsestraat 59, B-3000 Leuven, BelgiumSearch for more papers by this authorA. DE LOOF, A. DE LOOF Department of Biology, University of Leuven, Naamsestraat 59, B-3000 Leuven, BelgiumSearch for more papers by this authorJ.VANDEN BROECK, J.VANDEN BROECK Department of Biology, University of Leuven, Naamsestraat 59, B-3000 Leuven, BelgiumSearch for more papers by this authorL. SCHOOFS, L. SCHOOFS Department of Biology, University of Leuven, Naamsestraat 59, B-3000 Leuven, BelgiumSearch for more papers by this authorM. CLAEYS, M. CLAEYS Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, BelgiumSearch for more papers by this authorJ.-M. PASTEELS, J.-M. PASTEELS Departments of Biochemistry and Biology, University of Brussels, Brussels, BelgiumSearch for more papers by this authorD. DALOZE, D. DALOZE Departments of Biochemistry and Biology, University of Brussels, Brussels, BelgiumSearch for more papers by this author First published: 07 February 2006 https://doi.org/10.1111/j.1749-6632.1998.tb10877.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume839, Issue1TRENDS IN COMPARATIVE ENDOCRINOLOGY AND NEUROBIOLOGY: FROM MOLECULAR TO INTEGRATIVE BIOLOGYMay 1998Pages 571-573 RelatedInformation

Identification of G protein-coupled receptors in insect cells.

Communication processes lay at the very basis of physiological functioning and therefore, probably at the true basis of Life itself (as outlined by De Loof and Vanden Broeck1). All communication systems, including modern forms of human communication as well as biological communication systems, are based on similar fundamental principles or requirements and typically consist of the following three main parts: (1) the environment or a “sender-encoder” system which produces a signal or a message that is transmitted via a (2) “communication channel” towards a (3) “receiver-decoder-amplifier-responder.”2 In biological systems, physiological responses to extracellular signals and messages are generated by a process called signal transduction which is elicited by activation of specific receptor proteins. Interestingly, the four main classes of signaltransducing receptor proteins (ligand-gated ion channels, single-transmembrane proteins, seven-transmembrane G protein–coupled receptors [GPCRs], and nuclear receptors) are present in all metazoans.3 This review deals with the different kinds of GPCRs already identified in insect cells.