The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
Pat Simpson - One of the best experts on this subject based on the ideXlab platform.
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the achaete Scute complex in diptera patterns of noncoding sequence evolution
Journal of Evolutionary Biology, 2015Co-Authors: Bárbara Negre, Pat SimpsonAbstract:The achaete-Scute complex (AS-C) has been a useful paradigm for the study of pattern formation and its evolution. achaete-Scute genes have duplicated and evolved distinct expression patterns during the evolution of cyclorraphous Diptera. Are the expression patterns in different species driven by conserved regulatory elements? If so, when did such regulatory elements arise? Here, we have sequenced most of the AS-C of the fly Calliphora vicina (including the genes achaete, Scute and lethal of Scute) to compare noncoding sequences with known cis-regulatory sequences in Drosophila. The organization of the complex is conserved with respect to Drosophila species. There are numerous small stretches of conserved noncoding sequence that, in spite of high sequence turnover, display binding sites for known transcription factors. Synteny of the blocks of conserved noncoding sequences is maintained suggesting not only conservation of the position of regulatory elements but also an origin prior to the divergence between these two species. We propose that some of these enhancers originated by duplication with their target genes.
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Evolution of the achaete-Scute complex in insects: convergent duplication of proneural genes.
Trends in genetics : TIG, 2009Co-Authors: Bárbara Negre, Pat SimpsonAbstract:Proneural genes encode transcriptional activators of the basic Helix–loop–helix class that are involved in neuronal specification and differentiation. We have used the recent availability of genome sequences of multiple distant insect species to study the evolution of a family of proneural genes, the achaete - Scute genes, and to examine their genomic organization and evolution. We document independent evolution of multiple copies of achaete-Scute homologues and argue that this might have contributed to morphological diversity in Diptera and Lepidoptera.
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A conserved trans-regulatory landscape for Scute expression on the notum of cyclorraphous Diptera
Development Genes and Evolution, 2006Co-Authors: Joanna Richardson, Pat SimpsonAbstract:Bristles on the notum of many cyclorraphous flies are arranged into species-specific stereotyped patterns. The positions of bristles correlate with differences in the spatial expression of the Scute (sc) gene in those species examined so far. However, a major upstream activator of Scute , Pannier (Pnr), is expressed in a conserved domain over the entire medial notum. Here we examine the expression patterns in Calliphora vicina of stripe ( sr ), u-shaped ( ush ), caupolican ( caup ) and wingless ( wg ), genes known to modify the activity of Pnr or to act downstream of Pnr in Drosophila . We find that, with minor differences, their expression patterns are conserved. This suggests that the function of a trans -regulatory network of genes is relatively unchanged in derived Diptera and that many differences are likely to be due to changes in cis -regulatory sequences of Scute .
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genetic analysis of bristle loss in hybrids between drosophila melanogaster and d simulans provides evidence for divergence of cis regulatory sequences in the achaete Scute gene complex
Developmental Biology, 2000Co-Authors: Nick Skaer, Pat SimpsonAbstract:The two closely related species of Drosophila, D. melanogaster and D. simulans, display an identical bristle pattern on the notum, but hybrids between the two are lacking a variable number of bristles. We show that the loss is temperaturedependent and provide evidence for two periods of temperature sensitivity. A first period of heat sensitivity occurs during larval development and corresponds to the time when the prepattern of expression of genes whose products activate achaete‐Scute in the proneural clusters preceding bristle precursor formation is established. A second period of cold sensitivity corresponds to the time of emergence of the bristle precursor cells and the maintenance of their neural fate, a process requiring high levels of Achaete‐Scute. Expression of achaete‐Scute at these two critical periods depends on cis-regulatory elements of the achaete‐Scute complex (AS-C). The differences between males, which have only one copy of the X-linked AS-C from D. simulans, and females, which have copies from both parental species, are compared, together with the effects of crossing in different rearrangements of the D. melanogaster AS-C that delete regulatory and/or coding sequences. We provide evidence that bristle loss in the hybrids may result from a decrease in the level of transcription at the AS-C and argue that interaction between trans-acting factors and cis-regulatory elements within the AS-C has diverged between the two species. © 2000 Academic Press
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expression of achaete Scute homologues in discrete proneural clusters on the developing notum of the medfly ceratitis capitata suggests a common origin for the stereotyped bristle patterns of higher diptera
Development, 2000Co-Authors: Corinna Wulbeck, Pat SimpsonAbstract:The stereotyped positioning of sensory bristles in Drosophila has been shown to result from complex spatiotemporal regulation of the proneural achaete-Scute genes, that relies on an array of cis-regulatory elements and spatially restricted transcriptional activators such as Pannier. Other species of derived schizophoran Diptera have equally stereotyped, but different, bristle patterns. Divergence of bristle patterns could arise from changes in the expression pattern of proneural genes, resulting from evolution of the cis-regulatory sequences and/or altered expression patterns of transcriptional regulators. Here we describe the isolation of achaete-Scute homologues in Ceratitis capitata, a species of acalyptrate Schizophora whose bristle pattern differs slightly from that of Drosophila. At least three genes, Scute, lethal of Scute and asense have been conserved, thus demonstrating that gene duplication within the achaete-Scute complex preceded the separation of the families Drosophilidae and Tephritidae, whose common ancestor goes back more than 100 million years. The expression patterns of these genes provide evidence for conservation of many cis-regulatory elements as well as a common origin for the stereotyped patterns seen on the scutum of many Schizophora. Some aspects of the transcriptional regulation have changed, however, and correlate in the notum with differences in the bristle pattern. The Ceratitis pannier gene was isolated and displays a conserved expression domain in the notum.
Michael Chopp - One of the best experts on this subject based on the ideXlab platform.
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vascular endothelial growth factor mediates atorvastatin induced mammalian achaete Scute homologue 1 gene expression and neuronal differentiation after stroke in retired breeder rats
Neuroscience, 2006Co-Authors: Jieli Chen, Alex Zacharek, Chunling Zhang, J Ding, Cynthia Roberts, Alissa Kapke, Michael ChoppAbstract:Abstract Neurogenesis declines with advancing age. The mammalian achaete-Scute homologue-1 encodes a basic helix–loop–helix transcription factor, which controls neuronal differentiation. In this study, we first tested whether atorvastatin treatment enhances neurological functional outcome and neuronal differentiation after stroke in retired breeder 12 month rats. Rats were subjected to middle cerebral artery occlusion and treated with or without atorvastatin (3 mg/kg) for 7 days. Atorvastatin significantly increased expression of mammalian achaete-Scute homologue-1, β-tubulin III, and vascular endothelial growth factor in the ischemic brain, and concomitantly improved functional outcome compared with middle cerebral artery occlusion control rats. Increased neurogenesis significantly correlated with functional recovery after stroke. To further investigate the mechanisms of atorvastatin-induced neuronal differentiation, experiments were performed on neurospheres derived from retired breeder rat subventricular zone cells. Atorvastatin increased neuronal differentiation and upregulated vascular endothelial growth factor and mammalian achaete-Scute homologue-1 gene expression in cultured neurospheres. Vascular endothelial growth factor–treated neurospheres significantly increased mammalian achaete-Scute homologue-1 and β-tubulin III expression. Inhibition of vascular endothelial growth factor decreased atorvastatin-induced mammalian achaete-Scute homologue-1 and β-tubulin III expression. These data indicate that atorvastatin increases neuronal differentiation in retired breeder rats. In addition, atorvastatin upregulation of vascular endothelial growth factor expression, influences mammalian achaete-Scute homologue-1 transcription factor, which in turn, facilitates an increase in subventricular zone neuronal differentiation. These atorvastatin-mediated molecular events may contribute to the improved functional outcome in retired breeder rats subjected to stroke.
Ellen R Wald - One of the best experts on this subject based on the ideXlab platform.
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Acute Otitis Media and Acute Bacterial Sinusitis
2016Co-Authors: Ellen R WaldAbstract:Acute otitis media and acute bacterial sinusitis are 2 of the most common indications for antimicrobial agents in children. Together, they are responsible for billions of dollars of health care expenditures. The pathogenesis of the 2 conditions is identical. In the majority of children with each condition, a preceding viral upper respiratory tract infection predisposes to the development of the acute bacterial complication. It has been shown that viral upper respiratory tract infection predisposes to the development of acute otitis media in 37% of cases. Currently, precise microbiologic diagnosis of acute otitis media and acute bacterial sinusitis requires performance of tympanocentesis in the former and sinus aspiration in the latter. The identification of a virus from the nasopharynx in either case does not obviate the need for antimicrobial therapy. Furthermore, nasal and nasopharyngeal swabs are not useful in predicting the results of culture of the middle ear or paranasal sinus. However, it is possible that a combination of information regarding nasopharyngeal colonization with bacteria and infection with specific viruses may inform treatment decisions in the future. Acute otitis media (AOM) is the most common in-dication for the use of antimicrobial agents in children [1]. Acute bacterial sinusitis is the fifth most common indication for antibiotics [2]. Together, they are re
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acute otitis media and acute bacterial sinusitis
Clinical Infectious Diseases, 2011Co-Authors: Ellen R WaldAbstract:Acute otitis media and acute bacterial sinusitis are 2 of the most common indications for antimicrobial agents in children. Together, they are responsible for billions of dollars of health care expenditures. The pathogenesis of the 2 conditions is identical. In the majority of children with each condition, a preceding viral upper respiratory tract infection predisposes to the development of the acute bacterial complication. It has been shown that viral upper respiratory tract infection predisposes to the development of acute otitis media in 37% of cases. Currently, precise microbiologic diagnosis of acute otitis media and acute bacterial sinusitis requires performance of tympanocentesis in the former and sinus aspiration in the latter. The identification of a virus from the nasopharynx in either case does not obviate the need for antimicrobial therapy. Furthermore, nasal and nasopharyngeal swabs are not useful in predicting the results of culture of the middle ear or paranasal sinus. However, it is possible that a combination of information regarding nasopharyngeal colonization with bacteria and infection with specific viruses may inform treatment decisions in the future.
Laurens G Van Der Flier - One of the best experts on this subject based on the ideXlab platform.
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transcription factor achaete Scute homologue 2 initiates follicular t helper cell development
Nature, 2014Co-Authors: Xin Chen, Aibo Wang, Roza Nurieva, Xiaohu Wang, Bo Zhong, Ping Chen, Laurens G Van Der FlierAbstract:In immune responses, activated T cells migrate to B-cell follicles and develop into follicular T-helper (TFH) cells, a recently identified subset of CD4(+) T cells specialized in providing help to B lymphocytes in the induction of germinal centres. Although Bcl6 has been shown to be essential in TFH-cell function, it may not regulate the initial migration of T cells or the induction of the TFH program, as exemplified by C-X-C chemokine receptor type 5 (CXCR5) upregulation. Here we show that expression of achaete-Scute homologue 2 (Ascl2)--a basic helix-loop-helix (bHLH) transcription factor--is selectively upregulated in TFH cells. Ectopic expression of Ascl2 upregulates CXCR5 but not Bcl6, and downregulates C-C chemokine receptor 7 (CCR7) expression in T cells in vitro, as well as accelerating T-cell migration to the follicles and TFH-cell development in vivo in mice. Genome-wide analysis indicates that Ascl2 directly regulates TFH-related genes whereas it inhibits expression of T-helper cell 1 (TH1) and TH17 signature genes. Acute deletion of Ascl2, as well as blockade of its function with the Id3 protein in CD4(+) T cells, results in impaired TFH-cell development and germinal centre response. Conversely, mutation of Id3, known to cause antibody-mediated autoimmunity, greatly enhances TFH-cell generation. Thus, Ascl2 directly initiates TFH-cell development.
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transcription factor achaete Scute homologue 2 initiates follicular t helper cell development
Nature, 2014Co-Authors: Xin Chen, Aibo Wang, Roza Nurieva, Xiaohu Wang, Bo Zhong, Ping Chen, Laurens G Van Der FlierAbstract:In immune responses, activated T cells migrate to B-cell follicles and develop into follicular T-helper (TFH) cells, a recently identified subset of CD4(+) T cells specialized in providing help to B lymphocytes in the induction of germinal centres. Although Bcl6 has been shown to be essential in TFH-cell function, it may not regulate the initial migration of T cells or the induction of the TFH program, as exemplified by C-X-C chemokine receptor type 5 (CXCR5) upregulation. Here we show that expression of achaete-Scute homologue 2 (Ascl2)--a basic helix-loop-helix (bHLH) transcription factor--is selectively upregulated in TFH cells. Ectopic expression of Ascl2 upregulates CXCR5 but not Bcl6, and downregulates C-C chemokine receptor 7 (CCR7) expression in T cells in vitro, as well as accelerating T-cell migration to the follicles and TFH-cell development in vivo in mice. Genome-wide analysis indicates that Ascl2 directly regulates TFH-related genes whereas it inhibits expression of T-helper cell 1 (TH1) and TH17 signature genes. Acute deletion of Ascl2, as well as blockade of its function with the Id3 protein in CD4(+) T cells, results in impaired TFH-cell development and germinal centre response. Conversely, mutation of Id3, known to cause antibody-mediated autoimmunity, greatly enhances TFH-cell generation. Thus, Ascl2 directly initiates TFH-cell development.
Cees B M Oudejans - One of the best experts on this subject based on the ideXlab platform.
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the human achaete Scute homologue 2 ascl2 hash2 maps to chromosome 11p15 5 close to igf2 and is expressed in extravillus trophoblasts
Human Molecular Genetics, 1997Co-Authors: Marielle Alders, Matthew D Hodges, Annakaterina Hadjantonakis, Jan Postmus, Inge J Van Wijk, J Bliek, Maurice De Meulemeester, A Westerveld, Francois Guillemot, Cees B M OudejansAbstract:Here we describe the cloning of the human Achaete Scute Homologue 2 (HASH2) gene, officially designated ASCL2 (Achaete Scute complex like 2), a homologue of the Drosophila Achaete and Scute genes. In mouse, this gene is imprinted and maps to chromosome 7. We mapped the human homologue close to IGF2 and H19 at 11p15.5, the human region syntenic with mouse chromosome 7, indicating that this imprinted region is highly conserved in mouse and man. HASH2 is expressed in the extravillus trophoblasts of the developing placenta only. The lack of HASH2 expression in non-malignant hydatidiform (androgenetic) moles indicates that HASH2 is also imprinted in man.
