Effect of AGM and Fetal Liver-Derived Stromal Cell Lines on Globin Expression in Adult Baboon (P. anubis) Bone Marrow-Derived Erythroid Progenitors

This study was performed to investigate the hypothesis that the erythroid micro-environment plays a role in regulation of globin gene expression during adult erythroid differentiation. Adult baboon bone marrow and human cord blood CD34+ progenitors were grown in methylcellulose, liquid media, and in co-culture with stromal cell lines derived from different developmental stages in identical media supporting erythroid differentiation to examine the effect of the micro-environment on globin gene expression. Adult progenitors express high levels of γ-globin in liquid and methylcellulose media but low, physiological levels in stromal cell co-cultures. In contrast, γ-globin expression remained high in cord blood progenitors in stromal cell line co-cultures. Differences in γ-globin gene expression between adult progenitors in stromal cell line co-cultures and liquid media required cell-cell contact and were associated with differences in rate of differentiation and γ-globin promoter DNA methylation. We conclude that γ-globin expression in adult-derived erythroid cells can be influenced by the micro-environment, suggesting new potential targets for HbF induction

Mouse Ribosomal RNA Genes Contain Multiple Differentially Regulated Variants

Previous cytogenetic studies suggest that various rDNA chromosomal loci are not equally active in different cell types. Consistent with this variability, rDNA polymorphism is well documented in human and mouse. However, attempts to identify molecularly rDNA variant types, which are regulated individually (i.e., independent of other rDNA variants) and tissue-specifically, have not been successful. We report here the molecular cloning and characterization of seven mouse rDNA variants (v-rDNA). The identification of these v-rDNAs was based on restriction fragment length polymorphisms (RFLPs), which are conserved among individuals and mouse strains. The total copy number of the identified variants is less than 100 and the copy number of each individual variant ranges from 4 to 15. Sequence analysis of the cloned v-rDNA identified variant-specific single nucleotide polymorphisms (SNPs) in the transcribed region. These SNPs were used to develop a set of variant-specific PCR assays, which permitted analysis of the v-rDNAs' expression profiles in various tissues. These profiles show that three v-rDNAs are expressed in all tissues (constitutively active), two are expressed in some tissues (selectively active), and two are not expressed (silent). These expression profiles were observed in six individuals from three mouse strains, suggesting the pattern is not randomly determined. Thus, the mouse rDNA array likely consists of genetically distinct variants, and some are regulated tissue-specifically. Our results provide the first molecular evidence for cell-type-specific regulation of a subset of rDNA

Supernumerary chromosome variation and heterochromatin distribution in the endemic New Zealand frog Leiopelma hochstetteri

Specimens of the endemic New Zealand frog Leiopelma hochstetteri from Tapu on North Island were found to have six, nine or ten supernumerary chromosomes in their karyotypes. In comparison with previously published data, these results further indicate probable geographic variation in supernumerary chromosome number between populations. Increased numbers of supernumeraries in these frogs is correlated with apparent decrease of centromeric heterochromatin in the five large metacentric chromosomes of the karyotype, as detected by C-banding. Meiosis was abnormal in a male with a high number of supernumeraries. In lampbrush preparations from a single female with one supernumerary univalent, the supernumerary often had a denser, beaded appearance in comparison with the regular bivalents. Evidence is consistent with the notion that these supernumerary chromosomes may have arisen from centromeric fragments.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47362/1/412_2004_Article_BF00293180.pd

FCC-ee: The Lepton Collider: Future Circular Collider Conceptual Design Report Volume 2

In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today’s technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics

FCC Physics Opportunities: Future Circular Collider Conceptual Design Report Volume 1

We review the physics opportunities of the Future Circular Collider, covering its e+e-, pp, ep and heavy ion programmes. We describe the measurement capabilities of each FCC component, addressing the study of electroweak, Higgs and strong interactions, the top quark and flavour, as well as phenomena beyond the Standard Model. We highlight the synergy and complementarity of the different colliders, which will contribute to a uniquely coherent and ambitious research programme, providing an unmatchable combination of precision and sensitivity to new physics

Formation of nuclear heterochromatin: the nucleolar point of view

Establishment and inheritance of heterochromatic states is critical in maintaining genome integrity and gene expression state. The elucidation of the mechanisms implicated in these processes is fundamental to understand the control of epigenetic regulation of the genome. Recently, the nucleolus emerged as an important component of the nuclear architecture. Although the nucleolus is the most active site of cellular transcription, it is also an attractive compartment for nuclear heterochromatic regions, such as pericentric repeats, inactive X chromosome and regions with low gene density significantly enriched in repressed genes. The coexistence of euchromatic and heterochromatic rRNA genes in each cell reflects these two opposite functions of the nucleolus. An epigenetic network that is controlled by NoRC complex establishes and maintains rDNA heterochromatin. It is here discussed how heterochromatic rRNA genes and the associated epigenetic regulatory activities might mediate formation and inheritance of nuclear heterochromatic regions. Finally, we propose that the analysis of the components of heterochromatic rRNA genes will be not only relevant to understand the general composition of heterochromatin but has the potential to provide important and novel insights of how nuclear heterochromatic structures are established and inherited