Search

We provide here the sub-clustering results for each major cell type forthe manuscript: Kuppe, Ramirez Flores, Li et al. "Spatial multi-omic map of human myocardial infarction", 2022. The cells from snRNA-seq and snATAC-seq were first integrated and then sub-clustering was performed based on the integrated data. We tried our best to annotated the obtained sub-clusters.

We provide here the raw data of visium forthe manuscript: Kuppe, Ramirez Flores, Li et al. "Spatial multi-omic map of human myocardial infarction", 2022

63 p. with Internet appendix ; Includes bibliographical references (pp. 26-27) ; November 12, 2020 ; Massa and Schumacher are grateful for research support from the Social Sciences and Humanities Research Council of Canada (SSHRC; grant number 435-2015-0615). We highlight an important but overlooked characteristic of financial fragility: “fragile” stocks are more liquid because they are sensitive to non-fundamental liquidity shocks. This makes them less sensitive to corporate actions with price impact and therefore affects firms’ incentives to engage in those actions. We show that fragile firms have lower share repurchases but invest more, the effects stronger for financially constrained firms. We establish causality by relying on exogenous changes in fragility induced by mergers of asset managers with portfolio overlap in the stocks. Our results suggest that financial fragility has direct but unexpected real implications for corporate actions. Valuation Insight: Stocks that are financially fragile face liquidity risk that is not fundamental. Price fluctuations then are more likely a result of value-neutral events. As a result, corporate actions that are value-relevant are more easily confused with value-neutral events and have less of a market impact. This provides a screen for corporate actions. These may in some cases have a more positive effect on value because of a smaller market response.

Ziel der Dissertation war es, die Rolle des Transkriptionsfaktors PRO44 in der Regulation der Fruchtkörperentwicklung von \(\textit {Sordaria macrospora}\) zu identifizieren. Dafür wurden Hefe-2-Hybrid-Analysen und RNA-Seq-Analysen durchgeführt. Dabei konnte durch die Hefe-2-Hybrid-Studien eine Oligomerisierung von \(\it PRO44\) festgestellt werden. Ebenfalls wurde festgestellt, dass das pro44-Gen alternativ gespleißt wird. In den RNA-Seq-Analysen wurde RNA aus Proben verwendet, die mittels Laser-Mikrodissektion aus Protoperithezien von \(\textit {S. macrospoa}\) gewonnen wurde. Als Zielgene von PRO44 konnten die Gene identifiziert werden, welche für die Carbonanhydrase CAS4 und einen pilzspezifischen Transkriptionsfaktor codieren. Ebenso stellte sich heraus, dass Zielgene von PRO44 häufig in extrazelluläre Prozesse involviert sind. PRO44 reguliert die Fruchtkörperentwicklung von \(\textit {S. macrospoa}\) als Teil eines Netzwerkes mit anderen regulatorischen Proteinen.

\(\bf Background:\) Fungal fruiting bodies are complex three-dimensional structures that are formed to protect and disperse the sexual spores. Their morphogenesis requires the concerted action of numerous genes; however, at the molecular level, the spatio-temporal sequence of events leading to the mature fruiting body is largely unknown. In previous studies, the transcription factor gene pro44 and the histone chaperone gene asf1 were shown to be essential for fruiting body formation in the ascomycete Sordaria macrospora. Both PRO44 and ASF1 are predicted to act on the regulation of gene expression in the nucleus, and mutants in both genes are blocked at the same stage of development. Thus, we hypothesized that PRO44 and ASF1 might be involved in similar aspects of transcriptional regulation. In this study, we characterized their roles in fruiting body development in more detail. \(\bf Results:\) The PRO44 protein forms homodimers, localizes to the nucleus, and is strongly expressed in the outer layers of the developing young fruiting body. Analysis of single and double mutants of asf1 and three other chromatin modifier genes, cac2, crc1, and rtt106, showed that only asf1 is essential for fruiting body formation whereas cac2 and rtt106 might have redundant functions in this process. RNA-seq analysis revealed distinct roles for asf1 and pro44 in sexual development, with asf1 acting as a suppressor of weakly expressed genes during morphogenesis. This is most likely not due to global mislocalization of nucleosomes as micrococcal nuclease-sequencing did not reveal differences in nucleosome spacing and positioning around transcriptional start sites between \(\Delta\)asf1 and the wild type. However, bisulfite sequencing revealed a decrease in DNA methylation in \(\Delta\)asf1, which might be a reason for the observed changes in gene expression. Transcriptome analysis of gene expression in young fruiting bodies showed that pro44 is required for correct expression of genes involved in extracellular metabolism. Deletion of the putative transcription factor gene asm2, which is downregulated in young fruiting bodies of Δpro44, results in defects during ascospore maturation. \(\bf Conclusions:\) In summary, the results indicate distinct roles for the transcription factor PRO44 and the histone chaperone ASF1 in the regulation of sexual development in fungi.

Figure S15. Morphological characterization of Δasm2 (ΔSMAC_09436, spore isolate S148783) and a complemented transformant (spore isolate RL726). Strains were grown on full medium (BMM) or defined medium (SWG) at 25 °C for the indicated times. Scale bars are the same for all overview (left column for each time point, top view of perithecia growing on the surface of the agar medium) and detail (right column for each time point, side view of perithecia growing on the surface of the agar medium) pictures. In the asm2 deletion strain as well as the complemented transformant, perithecia are sometimes not arranged perpendicular to the growth surface as in the wild type (red arrows). (PDF 5730 kb)

Figure S7. Analysis of subcellular localization of RTT106, CAC2, and CRC1 by fluorescence microscopy. A. Nuclear localization of RTT106 and CAC2. Both genes were fused with egfp and co-transformed with plasmid pRH2B expressing a tdTomato-labelled histone. RTT106 and CAC2 co-localize with the histone in the nucleus. Growth 2d on slides with BMM, scale bar 20 μm. pRH2B contains genes for histone H2B fused with tdTomato (Teichert et al. 2014, PLoS Genet. 10:e1004582). B. Nuclear localization of CRC1. crc1 fused with egfp and expressed from plasmid pSMAC_02795_EGFP. CRC1 co-localizes with the DAPI-labelled nuclei. Growth 2d on slides with BMM, scale bar 10 μm. (PDF 3836 kb)

Figure S5. Southern blot analysis of Δcrc1 double mutants. A. Overview of the genomic locus in the different deletion mutants, with the probe for the Southern blot indicated. b. Southern blot analysis of the wild type and the Δcrc1, Δrtt106 double mutant S126403 after digestion of genomic DNA with HindIII. The blot was probed with the hph cassette. The resulting signals are as expected for the double mutant (6.8 kb band for the Δcrc1 locus and 3.7 kb band for the Δrtt106 locus) and the wild type (no signal). C. Southern blot analysis of the wild type and single ascospore isolates from crosses of Δcrc1 and Δasf1, or Δcrc1 and Δcac2, respectively. Genomic DNA was digested with HindIII. The blot was probed with the hph cassette. Double mutants Δcrc1, Δasf1 can be identified by bands at 6.8 kb for the Δcrc1 deletion and 3.5 kb band for the Δasf1 deletion. Double mutants Δcrc1, Δcac2 can be identified by bands at 6.8 kb for the Δcrc1 deletion and 4.2 kb band for the Δcac2 deletion. Double deletion strains that were used in further experiments are labelled in red. (PDF 1061 kb)

Table S5. Plasmids used in this study. (PDF 270 kb)

Figure S4. Southern blot analysis of Δcrc1 strains. A. Overview of the crc1 genomic locus in the wild type and the corresponding deletion mutant, with the probes for the Southern blot indicated. B. Southern blot analysis of the wild type, one primary transformant (T124.1) and nine single spore isolates of two different independent primary transformants after digestion of genomic DNA with the indicated enzymes. The blots were probed with the indicated probes. The resulting signals are as expected for the crc1 deletion for strains T124.1, S123582, S123587, S123615, S123617, S123635, S123637, and S123704 (6.8 kb band when probed with the deletion cassette, and no signal when probed with the gene-specific probe, whereas the wild type and non-deletion-carrying transformants give bands of 3.7 and 4.6 kb when probed with the deletion cassette, and a 8.2 kb band with the gene-specific probe). Deletion strains that were used in further experiments are labelled in red. (PDF 1362 kb)

Figure S6. Phylogenetic analysis of CRC subunit-containig proteins in ascomycetes. Protein sequences were aligned with Clustal X, and a Neighbor Joining analysis was performed with PAUP* with 1000 bootstrap replicates (bootstrap percentages are given at the branches). Sequences from the following ascomycetes were used for analysis with the CRC-subunit protein CC1G_08669 from the basidiomycete Coprinopsis cinerea (CC1G) as an outgroup: Aspergillus nidulans (ANID), Neurospora crassa (NCU), Pyronema confluens (PCON), Saccharomyces cerevisiae (S.c.), Schizosaccharomyces pombe (S.p.), Sclerotinia sclerotiorum (SS1G), Sordaria macrospora (SMAC), Stagonospora nodorum (SNOT), Tuber melanosporum (GSTUMT). The S. macrospora CRC1 protein is part of a cluster of proteins on a separate branch from the cluster containing the S. cerevisiae and S. pombe Rsc7 proteins. (PDF 131 kb)

Figure S8. Fruiting body development in chromatin modifier mutants. A. Strains were grown for 7 d on BMM at 25 °C. Photographs show fruiting body development on petri dishes, small boxes in lower left of each picture show enlarged sections of each overview. Scale bar in small boxes is 2 mm. B. Strains were grown for 7 d on SWG at 25 °C. Photographs show fruiting body development on petri dishes. (PDF 5774 kb)

Figure S3. Southern blot analysis of Δcac2, Δrtt106 double mutants. A. Overview of the cac2 and rtt106 genomic loci in the wild type and the corresponding deletion mutants, with the probes for the Southern blot indicated. B. Strains Δrtt106,fus and Δcac2 were crossed and single ascospore isolates were obtained. Three single spore isolates were subjected to Southern blot analysis after digestion of genomic DNA with the indicated enzymes. The blots were probed with the indicated probes. The resulting signals are as expected for the single and double mutants. Triangles indicate the weak bands in two cases, the asterisks in the blot probed with the rtt106 deletion cassette indicate undigested high molecular weight DNA. (PDF 1231 kb)

We study the decisions of international asset managers to outsource portfolio management of their funds and we link these decisions to market integration. Using a structural model of selfselection, we endogenize the decision to outsource in a comprehensive sample of international mutual funds and identify both performance and non-performance related determinants of outsourcing. Outsourcing fund management generates net positive gains to fund families of around 8-17 bp per month despite the ex-post underperformance of outsource funds relative to inhouse funds. Then, we establish that the performance improvements from outsourcing are directly related to segmentation in the underlying asset markets.