Absence of elevated anti-alpha-synuclein and anti-EBV latent membrane protein antibodies in PD.
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Antibodies, Viral↗
Biomedical subjects
M Vervoort
Publications and source records attributed to M Vervoort.
The evolution of the neural basic Helix-Loop-Helix proteins.
Basic Helix-Loop-Helix (bHLH) transcription factors control various aspects of the formation of the nervous system in the metazoans. In Drosophila some bHLH (such as the achaete-scuteatonal, and amos genes) act as proneural genes, directing ectodermal cells toward a neural fate. Their vertebrate orthologs, however, probably do not assume such a neural determination function, but rather control the decision made by neural precursors to generate neurons and not glial cells, as well as the progression of neuronal precursors toward differentiation into mature neurons. The proneural function of Drosophila bHLH genes may be an innovation that occurs in the evolutive lineage that leads to arthropods. In addition, although neural bHLH appear to be involved in the specification of neuronal identities, they probably do not confer by themselves neuronal type-specific properties to the cells. Rather, neural bHLH allow neural cells to correctly interpret specification and positional cues provided by other factors. Although bHLH genes are often expressed in complementary subsets of neural cells and/or expressed sequentially in those cells, the coding regions of the various neural bHLH appear largely interchangeable. We propose that the specific expression patterns have been acquired, following gene duplications, by subfunctionalization, i.e., the partitioning of ancestral expression patterns among the duplicates and, by extension, we propose that subfunctionalization is a key process to understand the evolution of neural bHLH genes.
Animals↗
Medical education in the new millennium--a Caribbean perspective.
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Adult↗
Release of tumor necrosis factor-alpha and prostanoids in whole blood cultures after in vivo exposure to low-dose aspirin.
BACKGROUND: The preventive effect of low-dose aspirin in cardiovascular disease is generally attributed to its antiplatelet action caused by differential inhibition of platelet cyclooxygenase-1. However, there is evidence that aspirin also affects release of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha). It is not known whether this is caused by direct action on the cytokine pathway or indirectly through cyclooxygenase inhibition and altered prostanoid synthesis, or both. METHODS: We assessed the capacity of lipopolysaccharide-activated leukocytes in whole blood cultures of eight healthy subjects following a single oral dose of 80 mg aspirin to release TNF-alpha, prostanoid E2 (PGE2) and prostanoid I2 (PGI2), and thromboxane A2 (TXA2). TNF-alpha and prostanoids were determined by enzyme-linked immunoassays. RESULTS: In seven subjects, TNF-alpha release in blood cultures decreased 24h after intake of aspirin. The effect of aspirin on prostanoid release was assessed in three individuals: PGE2 increased in all subjects, PGI2 increased in two and remained unchanged in one, and TXA2 was reduced in two and unchanged in one individual The presence of DFU, a specific inhibitor of cyclooxygenase 2, did not affect the reduction of TNF-alpha release by aspirin, but abolished prostanoid production in all three individuals. CONCLUSION: The capacity of activated leukocytes to release TNF-alpha is reduced by ingestion of low-dose aspirin, independent of changes in prostanoid biosynthesis.
Adult↗
The basic helix-loop-helix protein family: comparative genomics and phylogenetic analysis.
The basic Helix-Loop-Helix (bHLH) proteins are transcription factors that play important roles during the development of various metazoans including fly, nematode, and vertebrates. They are also involved in human diseases, particularly in cancerogenesis. We made an extensive search for bHLH sequences in the completely sequenced genomes of Caenorhabditis elegans and of Drosophila melanogaster. We found 35 and 56 different genes, respectively, which may represent the complete set of bHLH of these organisms. A phylogenetic analysis of these genes, together with a large number (>350) of bHLH from other sources, led us to define 44 orthologous families among which 36 include bHLH from animals only, and two have representatives in both yeasts and animals. In addition, we identified two bHLH motifs present only in yeast, and four that are present only in plants; however, the latter number is certainly an underestimate. Most animal families (35/38) comprise fly, nematode, and vertebrate genes, suggesting that their common ancestor, which lived in pre-Cambrian times (600 million years ago) already owned as many as 35 different bHLH genes.
Amino Acid Sequence↗
hedgehog and wing development in Drosophila: a morphogen at work?
In Drosophila, Hedgehog (Hh) is a key regulator of limb development and activates decapentaplegic (dpp), a gene encoding a TGFbeta-related factor that controls growth and patterning of the limbs. During wing development, Hh also has morphogen-like Dpp-independent functions, controlling the morphogenesis of the central part of the wing through the activation of the evolutionarily conserved transcription factors encoded by the iroquois and collier genes. The ways in which Hh forms an activity gradient to lay the basis of patterning of the adult wing are described here. As the signal transduction pathway of Hh is strongly conserved during evolution and human Hh may be implicated in congenital diseases and cancers, these observations provide important advances which may help in understanding the function of Hh proteins in normal and pathological development and tumourigenesis in humans.
Animals↗
The COE transcription factor Collier is a mediator of short-range Hedgehog-induced patterning of the Drosophila wing.
BACKGROUND: The secreted Hedgehog (Hh) proteins have been implicated as mediators of positional information in vertebrates and invertebrates. A gradient of Hh activity contributes to antero-posterior (A/P) patterning of the fly wing. In addition to inducing localised expression of Decapentaplegic (Dpp), which in turn relays patterning cues at long range, Hh directly patterns the central region of the wing. RESULTS: We show that short-range, dose-dependent Hh activity is mediated by activation of the transcription factor Collier (Col). In the absence of col activity, longitudinal veins 3 and 4 (L3 and L4) are apposed and the central intervein is missing. Hh expression induces col expression in a narrow stripe of cells along the A/P boundary through a dual-input mechanism: inhibition of proteolysis of Cubitus-interruptus (Ci) and activation of the Fused (Fu) kinase. Col, in cooperation with Ci, controls the formation of the central intervein by activating the expression of blistered (bs), which encodes the Drosophila serum response factor (D-SRF), the activity of which is required for the adoption and maintenance of the intervein cell fate. Furthermore, col is allelic to knot, a gene involved in the formation of the central part of the wing. This finding completes our understanding of the sectorial organisation of the Drosophila wing. CONCLUSIONS: Col, the Drosophila member of the COE family (Col/Olf-1/EBF) of non-basic, helix-loop-helix (HLH)-containing transcription factors, is a mediator of the short-range organising activity of Hh in the Drosophila wing. Our results support the idea that Hh controls target gene expression in a concentration-dependent manner and highlight the importance of the Fu kinase in this differential regulation. The high degree of evolutionary conservation of the COE proteins and the diversity of developmental processes controlled by Hh signalling raises the possibility that the specific genetic interactions depicted here may also operate in vertebrates.
Alleles↗
The bHLH genes in neural development.
Groups of genes sharing similar motifs may be used at different steps of a same developmental process. In this review, we discuss the significance of this phenomenon in the case of the basic Helix-Loop-Helix (bHLH) proteins that are involved at different steps of the development of the peripheral nervous system (PNS) of Drosophila.
Animals↗
Cell fate determination in Drosophila.
A major issue in development is to understand how local heterogeneities are interpreted to determine specific cell fates. The sense organs of Drosophila provide an accessible system for addressing this issue. Most sense organs comprise four types of cells, and their differentiation is the outcome of a complex developmental programme comprising several steps. Recent results illuminate, for several of these steps, the nature of the local heterogeneities and the mechanism used to interpret them in terms of cell fate decisions.
Animals↗
Genetic basis of the formation and identity of type I and type II neurons in Drosophila embryos.
The embryonic peripheral nervous system of Drosophila contains two main types of sensory neurons: type I neurons, which innervate external sense organs and chordotonal organs, and type II multidendritic neurons. Here, we analyse the origin of the difference between type I and type II in the case of the neurons that depend on the proneural genes of the achaete-scute complex (ASC). We show that, in Notch- embryos, the type I neurons are missing while type II neurons are produced in excess, indicating that the type I/type II choice relies on Notch-mediated cell communication. In contrast, both type I and type II neurons are absent in numb- embryos and after ubiquitous expression of tramtrack, indicating that the activity of numb and the absence of tramtrack are required to produce both external sense organ and multidendritic neural fates. The analysis of string- embryos reveals that when the precursors are unable to divide they differentiate mostly into type II neurons, indicating that the type II is the default neuronal fate. We also report a new mutant phenotype where the ASC-dependent neurons are converted into type II neurons, providing evidence for the existence of one or more genes required for maintaining the alternative (type I) fate. Our results suggest that the same mechanism of type I/type II specification may operate at a late step of the ASC-dependent lineages, when multidendritic neurons arise as siblings of the external sense organ neurons and, at an early step, when other multidendritic neurons precursors arise as siblings of external sense organ precursors.
Animals↗
Genetic determinants of sense organ identity in Drosophila: regulatory interactions between cut and poxn.
Two genes involved in defining the type of sense organ have been identified in Drosophila. The gene cut differentiates the external sense organs (where it is expressed) from the chordotonal organs (where it is not); among the external sense organs poxn differentiates the poly-innervated organs (where it is expressed) from the mono-innervated organs (where it is not). Here we show that the expression of poxn in normal embryos does not depend on cut, and that poxn is capable of inducing the expression of cut. We have identified a small domain of the very large cut regulatory region as a likely target for activation by poxn.
Animals↗