986 research outputs found

    A formula for the number of spanning trees in circulant graphs with non-fixed generators and discrete tori

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    We consider the number of spanning trees in circulant graphs of βn\beta n vertices with generators depending linearly on nn. The matrix tree theorem gives a closed formula of βn\beta n factors, while we derive a formula of β−1\beta-1 factors. Using the same trick, we also derive a formula for the number of spanning trees in discrete tori. Moreover, the spanning tree entropy of circulant graphs with fixed and non-fixed generators is compared.Comment: 8 pages, 2 figure

    Artery tertiary lymphoid organs control multi-layered territorialized atherosclerosis B cell responses in aged ApoE-/- mice

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    Objective: Explore aorta B cell immunity in aged ApoE-/- mice. Approach and Results: Transcript maps, FACS, immunofluorescence analyses, cell transfers, and Ig-ELISPOT assays showed multi-layered atherosclerosis B cell responses in artery tertiary lymphoid organs (ATLOs). Aging-associated aorta B cell-related transcriptomes were identified and transcript atlases revealed highly territorialized B cell responses in ATLOs versus atherosclerotic lesions: ATLOs showed upregulation of bona fide B cell genes including Cd19, Ms4a1 (Cd20), Cd79a/b, and Ighm though intima plaques preferentially expressed molecules involved in non-B effector responses towards B cell-derived mediators, i.e. Fcgr3 (Cd16), Fcer1g (Cd23), and the C1q family. ATLOs promoted B cell recruitment. ATLO B-2 B cells included naïve, transitional, follicular, germinal center, switched IgG1+, IgA+, and IgE+ memory cells, plasmablasts, and long-lived plasma cells (PCs). ATLOs recruited large numbers of B-1 cells whose subtypes were skewed towards IL-10+ B-1b cells versus IL-10- B-1a cells. ATLO B-1 cells and PCs constitutively produced IgM and IgG and a fraction of PCs expressed IL-10. Moreover, ApoE-/- mice showed increased germinal center B cells in renal lymph nodes, IgM-producing PCs in the bone marrow, and higher IgM and anti-MDA-LDL IgG serum titers. Conclusions: ATLOs orchestrate dichotomic, territorialized, and multi-layered B cell responses in the diseased aorta; germinal center reactions indicate generation of autoimmune B cells within the diseased arterial wall during aging

    The Ubiquitin Binding Domain ZnF UBP Recognizes the C-Terminal Diglycine Motif of Unanchored Ubiquitin

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    SummaryUbiquitin binding proteins regulate the stability, function, and/or localization of ubiquitinated proteins. Here we report the crystal structures of the zinc-finger ubiquitin binding domain (ZnF UBP) from the deubiquitinating enzyme isopeptidase T (IsoT, or USP5) alone and in complex with ubiquitin. Unlike other ubiquitin binding domains, this domain contains a deep binding pocket where the C-terminal diglycine motif of ubiquitin is inserted, thus explaining the specificity of IsoT for an unmodified C terminus on the proximal subunit of polyubiquitin. Mutations in the domain demonstrate that it is required for optimal catalytic activation of IsoT. This domain is present in several other protein families, and the ZnF UBP domain from an E3 ligase also requires the C terminus of ubiquitin for binding. These data suggest that binding the ubiquitin C terminus may be necessary for the function of other proteins

    Studying DNA Double-Strand Break Repair: An Ever-Growing Toolbox

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    To ward off against the catastrophic consequences of persistent DNA double-strand breaks (DSBs), eukaryotic cells have developed a set of complex signaling networks that detect these DNA lesions, orchestrate cell cycle checkpoints and ultimately lead to their repair. Collectively, these signaling networks comprise the DNA damage response (DDR). The current knowledge of the molecular determinants and mechanistic details of the DDR owes greatly to the continuous development of ground-breaking experimental tools that couple the controlled induction of DSBs at distinct genomic positions with assays and reporters to investigate DNA repair pathways, their impact on other DNA-templated processes and the specific contribution of the chromatin environment. In this review, we present these tools, discuss their pros and cons and illustrate their contribution to our current understanding of the DDR.European Research Council (ERC-2014-CoG 647344

    The distinct RNA-interaction modes of a small ZnF domain underlay TUT4(7) diverse action in miRNA regulation

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    TUT4 and the closely related TUT7 are non-templated poly(U) polymerases required at different stages of development, and their mis-regulation or mutation has been linked to important cancer pathologies. While TUT4(7) interaction with its pre-miRNA targets has been characterized in detail, the molecular bases of the broader target recognition process are unclear. Here, we examine RNA binding by the ZnF domains of the protein. We show that TUT4(7) ZnF2 contains two distinct RNA binding surfaces that are used in the interaction with different RNA nucleobases in different targets, i.e that this small domain encodes diversity in TUT4(7) selectivity and molecular function. Interestingly and unlike other well-characterized CCHC ZnFs, ZnF2 is not physically coupled to the flanking ZnF3 and acts independently in miRNA recognition, while the remaining CCHC ZnF of TUT4(7), ZnF1, has lost its intrinsic RNA binding capability. Together, our data suggest that the ZnFs of TUT4(7) are independent units for RNA and, possibly, protein-protein interactions that underlay the protein’s functional flexibility and are likely to play an important role in building its interaction network

    Contraction Mappings and Applications

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    The aim of the chapter is to find the existence results for the solution of non-homogeneous Fredholm integral equations of the second kind and non-linear matrix equations by using the fixed point theorems. Here, we derive fixed point theorems for two different type of contractions. Firstly, we utilize the concept of manageable functions to define multivalued α∗−η∗ manageable contractions and prove fixed point theorems for such contractions. After that, we use these fixed point results to find the solution of non-homogeneous Fredholm integral equations of the second kind. Secondly, we introduce weak F contractions named as α-F-weak-contraction to prove fixed point results in the setting of metric spaces and by using these results we find the solution for non-linear matrix equations

    ZNF274 Recruits the Histone Methyltransferase SETDB1 to the 3′ Ends of ZNF Genes

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    Only a small percentage of human transcription factors (e.g. those associated with a specific differentiation program) are expressed in a given cell type. Thus, cell fate is mainly determined by cell type-specific silencing of transcription factors that drive different cellular lineages. Several histone modifications have been associated with gene silencing, including H3K27me3 and H3K9me3. We have previously shown that genes for the two largest classes of mammalian transcription factors are marked by distinct histone modifications; homeobox genes are marked by H3K27me3 and zinc finger genes are marked by H3K9me3. Several histone methyltransferases (e.g. G9a and SETDB1) may be involved in mediating the H3K9me3 silencing mark. We have used ChIP-chip and ChIP-seq to demonstrate that SETDB1, but not G9a, is associated with regions of the genome enriched for H3K9me3. One current model is that SETDB1 is recruited to specific genomic locations via interaction with the corepressor TRIM28 (KAP1), which is in turn recruited to the genome via interaction with zinc finger transcription factors that contain a Kruppel-associated box (KRAB) domain. However, specific KRAB-ZNFs that recruit TRIM28 (KAP1) and SETDB1 to the genome have not been identified. We now show that ZNF274 (a KRAB-ZNF that contains 5 C2H2 zinc finger domains), can interact with KAP1 both in vivo and in vitro and, using ChIP-seq, we show that ZNF274 binding sites co-localize with SETDB1, KAP1, and H3K9me3 at the 3′ ends of zinc finger genes. Knockdown of ZNF274 with siRNAs reduced the levels of KAP1 and SETDB1 recruitment to the binding sites. These studies provide the first identification of a KRAB domain-containing ZNF that is involved in recruitment of the KAP1 and SETDB1 to specific regions of the human genome

    Identification of transcriptional regulators for the Ustilago maydis mig genes

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    The basidiomycete fungus Ustilago maydis is a plant pathogen. It can infect maize plants specifically and depends on the plant host for pathogenic development. This fungus has become an interesting research model for plant-fungus interactions. A maize induced gene family, the mig genes, has been identified in U. maydis. This gene family contains mig1, the mig2-1 to mig2-5 gene cluster, and mig2-6. All mig genes showed strongly plant induced expression patterns and were predicted to be involved in the plant-fungus interactions. Detailed analysis of the mig2-5 promoter has uncovered a consensus motif (5’-CCAC/AC/A-3’), which is present in multiple copies in all mig2 promoters and whose activity specifically depends on the sequence triplet 5’-CCA-3’ (5’-TGG-3’). On this basis, I considered C2H2 zinc finger and Myb proteins in U. maydis as potential regulators for mig genes. Candidate genes were analyzed by a PCR-based deletion approach. I could show that deletion of mzr1, which encodes a C2H2 zinc finger protein, strongly decreases the expression level of mig2-5 after plant inoculation. In addition, another C2H2 zinc finger protein called Biz1 has been found to be involved in the transcriptional activation of mig genes (M. Vranes and J. Kämper, unpublished). Conditional overexpression of both mzr1 and biz1 is sufficient to induce transcription of several mig genes under culture conditions. Furthermore, I could show that the truncated Mzr1 protein expressed in E. coli could specifically bind to the mig2-5 promoter in vitro. Apart from this, another C2H2 zinc finger protein, named Znf23, was found to be involved in mig gene regulations. I could show that the expression of mig genes in the znf23 deletion strain was stronger than in the wild type strain after plant infection. These results suggest that Mzr1 is a direct positive regulator to mig2-5, while Znf23 appears to negatively influence mig gene expression. The implications of these results are discussed

    The diverse requirements of ARS2 in nuclear cap-binding complex-dependent RNA processing

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    ARS2 is a stable component of the nuclear cap-binding complex (CBC) and is critical for RNA Polymerase II transcript processing. Moreover, ARS2, and its orthologue SERRATE in plants, has been implicated in having a role in most established CBC-dependent functions. This review will provide insight into the functions of ARS2/SERRATE in numerous RNA Polymerase II transcript processing events, which happen co-transcriptionally from initiation to termination, and post-transcriptionally during maturation and export into the cytoplasm. Additionally, we will discuss what is known regarding ARS2/SERRATE structure in plants and in mammals
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