40 research outputs found
Homologous association of the Bithorax-Complex during embryogenesis: consequences for transvection in Drosophila melanogaster
Transvection is the phenomenon by which the expression of a gene can be controlled by its homologous counterpart in trans, presumably due to pairing of alleles in diploid interphase cells. Transvection or trans-sensing phenomena have been reported for several loci in Drosophila, the most thoroughly studied of which is the Bithorax-Complex (BX-C). It is not known how early trans-sensing occurs nor the extent or duration of the underlying physical interactions. We have investigated the physical proximity of homologous genes of the BX-C during Drosophila melanogaster embryogenesis by applying fluorescent in situ hybridization techniques together with high resolution confocal light microscopy and digital image processing. The association of homologous alleles of the BX-C starts in nuclear division cycle 13, reaches a plateau of 70% in post-gastrulating embryos, and is not perturbed by the transcriptional state of the genes throughout embryogenesis. Pairing frequencies never reach 100% indicative that the homologous associations are in equilibrium with a dissociated state. We determined the effects of translocations and a zeste protein null mutation, both of which strongly diminish transvection phenotypes, on the extent of diploid homologue pairing. Surprisingly, the pairing of homologous alleles was reduced, albeit only to 20 - 30%, by translocating one allele of the BX-C from the right arm of chromosome 3 to the left arm of chromosome 3 or to the X chromosome although trans-regulation of the Ultrabithorax gene was abolished. A zeste protein null mutation neither delayed the onset of pairing nor led to unpairing of the homologous alleles. These data are discussed in light of different models for trans-regulation. We examined the onset of pairing of the chromosome 4 as well as of loci near the centromere of chromosome 3 and near the telomere of 3R in order to test models for the mechanism of homologue pairing
Molecular biology of histidine decarboxylase and prostaglandin receptors
Histamine and prostaglandins (PGs) play a variety of physiological roles as autacoids, which function in the vicinity of their sources and maintain local homeostasis in the body. They stimulate target cells by acting on their specific receptors, which are coupled to trimeric G proteins. For the precise understanding of the physiological roles of histamine and PGs, it is necessary to clarify the molecular mechanisms involved in their synthesis as well as their receptor-mediated responses. We cloned the cDNAs for mouse l-histidine decarboxylase (HDC) and 6 mouse prostanoid receptors (4 PGE2 receptors, PGF receptor, and PGI receptor). We then characterized the expression patterns and functions of these genes. Furthermore, we established gene-targeted mouse strains for HDC and PG receptors to explore the novel pathophysiological roles of histamine and PGs. We have here summarized our research, which should contribute to progress in the molecular biology of HDC and PG receptors
The Eurace@Unibi Model: An Agent-Based Macroeconomic Model for Economic Policy Analysis
Dawid H, Gemkow S, Harting P, van der Hoog S, Neugart M. The Eurace@Unibi Model: An Agent-Based Macroeconomic Model for Economic Policy Analysis. Working Papers in Economics and Management. Vol 05-2012. Bielefeld: Bielefeld University, Department of Business Administration and Economics; 2012.This document provides a description of the modeling assumptions and economic features
of the Eurace@Unibi model. Furthermore, the document shows typical patterns of
the output generated by this model and compares it to empirically observable stylized facts.
The Eurace@Unibi model provides a representation of a closed macroeconomic model with
spatial structure. The main objective is to provide a micro-founded macroeconomic model
that can be used as a unified framework for policy analysis in different economic policy areas
and for the examination of generic macroeconomic research questions. In spite of this general
agenda the model has been constructed with certain specific research questions in mind and
therefore certain parts of the model, e.g. the mechanisms driving technological change, have
been worked out in more detail than others.
The purpose of this document is to give an overview over the model itself and its features
rather than discussing how insights into particular economic issues can be obtained using the
Eurace@Unibi model. The model has been designed as a framework for economic analysis in
various domains of economics. A number of economic issues have been examined using (prior
versions of) the model (see Dawid et al. (2008), Dawid et al. (2009), Dawid et al. (2011a),
Dawid and Harting (2011), van der Hoog and Deissenberg (2011), Cincotti et al. (2010))
and recent extensions of the model have substantially extended its applicability in various
economic policy domains, however results of such policy analyses will be reported elsewhere.
Whereas the overall modeling approach, the different modeling choices and the economic
rationale behind these choices is discussed in some detail in this document, no detailed
description of the implementation is given. Such a detailed documentation is provided in the
accompanying document Dawid et al. (2011b)
Noncanonical Compensation of Zygotic X Transcription in Early Drosophila melanogaster Development Revealed through Single-Embryo RNA-Seq
Mmany genes from the X chromosome are expressed at the same level in female and male embryos during early Drosophila development, prior to the establishment of MSL-mediated dosage compensation, suggesting the existence of a novel mechanism
Identification of Genes That Promote or Antagonize Somatic Homolog Pairing Using a High-Throughput FISH–Based Screen
The pairing of homologous chromosomes is a fundamental feature of the meiotic cell. In addition, a number of species exhibit homolog pairing in nonmeiotic, somatic cells as well, with evidence for its impact on both gene regulation and double-strand break (DSB) repair. An extreme example of somatic pairing can be observed in Drosophila melanogaster, where homologous chromosomes remain aligned throughout most of development. However, our understanding of the mechanism of somatic homolog pairing remains unclear, as only a few genes have been implicated in this process. In this study, we introduce a novel high-throughput fluorescent in situ hybridization (FISH) technology that enabled us to conduct a genome-wide RNAi screen for factors involved in the robust somatic pairing observed in Drosophila. We identified both candidate “pairing promoting genes” and candidate “anti-pairing genes,” providing evidence that pairing is a dynamic process that can be both enhanced and antagonized. Many of the genes found to be important for promoting pairing are highly enriched for functions associated with mitotic cell division, suggesting a genetic framework for a long-standing link between chromosome dynamics during mitosis and nuclear organization during interphase. In contrast, several of the candidate anti-pairing genes have known interphase functions associated with S-phase progression, DNA replication, and chromatin compaction, including several components of the condensin II complex. In combination with a variety of secondary assays, these results provide insights into the mechanism and dynamics of somatic pairing
Current and Future Drug Targets in Weight Management
Obesity will continue to be one of the leading causes of chronic disease unless the ongoing rise in the prevalence of this condition is reversed. Accumulating morbidity figures and a shortage of effective drugs have generated substantial research activity with several molecular targets being investigated. However, pharmacological modulation of body weight is extremely complex, since it is essentially a battle against one of the strongest human instincts and highly efficient mechanisms of energy uptake and storage. This review provides an overview of the different molecular strategies intended to lower body weight or adipose tissue mass. Weight-loss drugs in development include molecules intended to reduce the absorption of lipids from the GI tract, various ways to limit food intake, and compounds that increase energy expenditure or reduce adipose tissue size. A number of new preparations, including combinations of the existing drugs topiramate plus phentermine, bupropion plus naltrexone, and the selective 5-HT2C agonist lorcaserin have recently been filed for approval. Behind these leading candidates are several other potentially promising compounds and combinations currently undergoing phase II and III testing. Some interesting targets further on the horizon are also discussed
Histaminergic system in brain disorders: lessons from the translational approach and future perspectives
Fly-FISHING: a protocol to localize single copy genes inside the nucleus in whole mount embryos
none availabl