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Financialization has become the go-to term for scholars grappling with the growth of finance. This Handbook offers the first comprehensive survey of the scholarship on financialization, connecting finance with changes in politics, technology, culture, society and the economy. It takes stock of the diverse avenues of research that comprise financialization studies and the contributions they have made to understanding the changes in contemporary societies driven by the rise of finance. The chapters chart the field's evolution from research describing and critiquing the manifestations of financialization towards scholarship that pinpoints the driving forces, mechanisms and boundaries of financialization. Written for researchers and students not only in economics but from across the social sciences and the humanities, this book offers a decidedly global and pluri-disciplinary view on financialization for those who are looking to understand the changing face of finance and its consequences.

Background The dilution-replicate experimental design for qPCR assays is especially efficient. It is based on multiple linear regression of multiple 3-point standard curves that are derived from the experimental samples themselves and thus obviates the need for a separate standard curve produced by serial dilution of a standard. The method minimizes the total number of reactions and guarantees that Cq values are within the linear dynamic range of the dilution-replicate standard curves. However, the lack of specialized software has so far precluded the widespread use of the dilution-replicate approach. Results Here we present repDilPCR, the first tool that utilizes the dilution-replicate method and extends it by adding the possibility to use multiple reference genes. repDilPCR offers extensive statistical and graphical functions that can also be used with preprocessed data (relative expression values) obtained by usual assay designs and evaluation methods. repDilPCR has been designed with the philosophy to automate and speed up data analysis (typically less than a minute from Cq values to publication-ready plots), and features automatic selection and performance of appropriate statistical tests, at least in the case of one-factor experimental designs. Nevertheless, the program also allows users to export intermediate data and perform more sophisticated analyses with external statistical software, e.g. if two-way ANOVA is necessary. Conclusions repDilPCR is a user-friendly tool that can contribute to more efficient planning of qPCR experiments and their robust analysis. A public web server is freely accessible at https://repdilpcr.eu without registration. The program can also be used as an R script or as a locally installed Shiny app, which can be downloaded from https://github.com/deyanyosifov/repDilPCR where also the source code is available.

Christoph Plass, Christopher Oakes and colleagues study genome-wide DNA methylation dynamics during B cell maturation and the pathogenic role of transcription factor dysregulation in chronic lymphocytic leukemia (CLL). By comparing normal and malignant B cells, they find that tumors derive from a continuum of maturation states, which correlate with different clinical outcomes. Charting differences between tumors and normal tissue is a mainstay of cancer research. However, clonal tumor expansion from complex normal tissue architectures potentially obscures cancer-specific events, including divergent epigenetic patterns. Using whole-genome bisulfite sequencing of normal B cell subsets, we observed broad epigenetic programming of selective transcription factor binding sites coincident with the degree of B cell maturation. By comparing normal B cells to malignant B cells from 268 patients with chronic lymphocytic leukemia (CLL), we showed that tumors derive largely from a continuum of maturation states reflected in normal developmental stages. Epigenetic maturation in CLL was associated with an indolent gene expression pattern and increasingly favorable clinical outcomes. We further uncovered that most previously reported tumor-specific methylation events are normally present in non-malignant B cells. Instead, we identified a potential pathogenic role for transcription factor dysregulation in CLL, where excess programming by EGR and NFAT with reduced EBF and AP-1 programming imbalances the normal B cell epigenetic program.

Objective To determine whether there is a correlation between the degree of the tibial plateau angle (TPA) and the incidence of medial meniscal tear (MMT) in dogs with complete cranial cruciate ligament (CCL) rupture observed at the time of arthrotomy. Methods 144 dogs met the inclusion criteria for this study with 88 (61.11%) found to have a MMT. Breed, age, sex, weight, affected limb, duration of lameness, and the integrity of contralateral stifle were recorded. Six groups were established based on TPA ranges measured in degrees. Results There was a one-fourth reduction in the number of MMT observed in dogs with a TPA between 35 to 37 degrees and an almost two-fold reduction in the number of MMT in dogs with a TPA greater than 38 degrees. There was a 6 times greater risk of MMT in those with acute lameness in comparison to those with a chronic lameness. Conclusion A relationship was found to exist between MMT and TPA with a lower prevalence of MMT in dogs with an excessive TPA. Chronic lameness was also associated with a lower prevalence of MMT regardless of TPA degree. In dogs with complete CCL tears, excessive TPA and chronic lameness were found to be statistically significant in relation to fewer MMT.

Objective Mislabelling and swapping of laboratory samples are handling errors that can lead to erroneous interpretation of data and/or patient harm. Sequenced samples can be traced back to the respective donors by matching of single nucleotide polymorphisms (SNPs). Frameworks and software to do this have been developed for use with whole genome/exome sequencing data but not for targeted next-generation sequencing (tNGS), possibly due to the limited genomic coverage with tNGS and the need for individualization of the set of interrogated SNPs. We decided to adapt a popular tool for use with tNGS data, to demonstrate the possibility of selecting informative SNPs from a typical tNGS panel and to create an automated workflow for detection of sample handling errors. Results We compiled a custom list of 28 SNPs and with its help we demonstrated the practicability of using only tNGS data to cost-effectively detect mislabelled samples. In two cohorts of totally 1441 patients with sequential samples, we could identify 3 sample swaps, 7 mislabelled samples (3 externally and 4 internally) and 1 mistake of unknown origin. We provide an R function for automated detection of sample swaps and mislabelling to the community as a free and open-source tool.

The complexities and contradictions of ‘green’ finance demand multidimensional perspectives in critical socioeconomic research. Current studies often remain fragmented, focusing either on global financial structures or micro-level practices without fully integrating both. This essay advocates for a more integrated analytical approach, employing three components: constructions, cleavages, and complementarities. At the micro-level, green finance is constructed by diverse actors, influencing macro-level financial governance and capital flows. Conversely, macro-structural shifts, driven by geopolitical and institutional dynamics, shape micro-level activities forging new alliances and oppositions – cleavages. Since the responses of actors and their institutional context to green finance are diverse, new institutional and agentic complementarities emerge. How green finance alters the relationship between financial markets and political-economic institutions, and how this unfolds across national economies, shapes our understanding of capitalist varieties and the emergence of new actors and networks. The essay contends that linking these dimensions and integrating micro- and macro-approaches enables scholarship to pursue a shared understanding of green finance and its (in)capacities to confront socioecological crises under financial capitalism.

Non-coding RNAs are much more common than previously thought. However, for the vast majority of non-coding RNAs, the cellular function remains enigmatic. The two long non-coding RNA (lncRNA) genes DLEU1 and DLEU2 map to a critical region at chromosomal band 13q14.3 that is recurrently deleted in solid tumors and hematopoietic malignancies like chronic lymphocytic leukemia (CLL). While no point mutations have been found in the protein coding candidate genes at 13q14.3, they are deregulated in malignant cells, suggesting an epigenetic tumor suppressor mechanism. We therefore characterized the epigenetic makeup of 13q14.3 in CLL cells and found histone modifications by chromatin-immunoprecipitation (ChIP) that are associated with activated transcription and significant DNA-demethylation at the transcriptional start sites of DLEU1 and DLEU2 using 5 different semi-quantitative and quantitative methods (aPRIMES, BioCOBRA, MCIp, MassARRAY, and bisulfite sequencing). These epigenetic aberrations were correlated with transcriptional deregulation of the neighboring candidate tumor suppressor genes, suggesting a coregulation in cis of this gene cluster. We found that the 13q14.3 genes in addition to their previously known functions regulate NF-kB activity, which we could show after overexpression, siRNA-mediated knockdown, and dominant-negative mutant genes by using Western blots with previously undescribed antibodies, by a customized ELISA as well as by reporter assays. In addition, we performed an unbiased screen of 810 human miRNAs and identified the miR-15/16 family of genes at 13q14.3 as the strongest inducers of NF-kB activity. In summary, the tumor suppressor mechanism at 13q14.3 is a cluster of genes controlled by two lncRNA genes that are regulated by DNA-methylation and histone modifications and whose members all regulate NF-kB. Therefore, the tumor suppressor mechanism in 13q14.3 underlines the role both of epigenetic aberrations and of lncRNA genes in human tumorigenesis and is an example of colocalization of a functionally related gene cluster.

Knowledge of the genomic landscape of chronic lymphocytic leukemia (CLL) grows increasingly detailed, providing challenges in contextualizing the accumulated information. To define the underlying networks, we here perform a multi-platform molecular characterization. We identify major subgroups characterized by genomic instability (GI) or activation of epithelial-mesenchymal-transition (EMT)-like programs, which subdivide into non-inflammatory and inflammatory subtypes. GI CLL exhibit disruption of genome integrity, DNA-damage response and are associated with mutagenesis mediated through activation-induced cytidine deaminase or defective mismatch repair. TP53 wild-type and mutated/deleted cases constitute a transcriptionally uniform entity in GI CLL and show similarly poor progression-free survival at relapse. EMT-like CLL exhibit high genomic stability, reduced benefit from the addition of rituximab and EMT-like differentiation is inhibited by induction of DNA damage. This work extends the perspective on CLL biology and risk categories in TP53 wild-type CLL. Furthermore, molecular targets identified within each subgroup provide opportunities for new treatment approaches. Chronic lymphocytic leukemia has been studied using multiple levels of omics data. Here, the authors use exome sequencing, SNP, protein and gene expression data to identify distinct biologic tumor subtypes with heterogeneous prognostic impact after chemo- or immunochemotherapy.

In chronic lymphocytic leukemia (CLL), a diverse set of genetic mutations is embedded in a deregulated epigenetic landscape that drives cancerogenesis. To elucidate the role of aberrant chromatin features, we mapped DNA methylation, seven histone modifications, nucleosome positions, chromatin accessibility, binding of EBF1 and CTCF, as well as the transcriptome of B cells from CLL patients and healthy donors. A globally increased histone deacetylase activity was detected and half of the genome comprised transcriptionally downregulated partially DNA methylated domains demarcated by CTCF. CLL samples displayed a H3K4me3 redistribution and nucleosome gain at promoters as well as changes of enhancer activity and enhancer linkage to target genes. A DNA binding motif analysis identified transcription factors that gained or lost binding in CLL at sites with aberrant chromatin features. These findings were integrated into a gene regulatory enhancer containing network enriched for B‐cell receptor signaling pathway components. Our study predicts novel molecular links to targets of CLL therapies and provides a valuable resource for further studies on the epigenetic contribution to the disease. Synopsis Transcriptome profiling and genome‐scale mapping of DNA methylation, seven histone modifications, nucleosome positions, chromatin accessibility, EBF1 and CTCF binding are performed in B cells from CLL patients and healthy donors. Altered chromatin features were detected at 80% of the differentially regulated genes in CLL and histone deacetylase activity was globally increased. Half of the CLL genome comprised partially DNA methylated domains that were transcriptionally downregulated, demarcated by CTCF and enriched for H3K9me3 and H3K27me3. H3K4me3 was redistributed at CLL promoters, including loss of bivalent H3K4me3/H3K27me3 states, and substantial changes of enhancer activity were detected. A gene regulatory network including enhancers was constructed around the transcription factors targeting 15 central binding motifs that were associated with aberrant CLL chromatin features. Genes involved in BCR signaling were enriched in the network. Graphical Abstract Transcriptome profiling and genome‐scale mapping of DNA methylation, seven histone modifications, nucleosome positions, chromatin accessibility, EBF1 and CTCF binding are performed in B cells from CLL patients and healthy donors.

Notch signaling plays a pivotal role in the development and, when dysregulated, it contributes to tumorigenesis. The amplitude and duration of the Notch response depend on the posttranslational modifications (PTMs) of the activated NOTCH receptor – the NOTCH intracellular domain (NICD). In normoxic conditions, the hydroxylase FIH (factor inhibiting HIF) catalyzes the hydroxylation of two asparagine residues of the NICD. Here, we investigate how Notch-dependent gene transcription is regulated by hypoxia in progenitor T cells. We show that the majority of Notch target genes are downregulated upon hypoxia. Using a hydroxyl-specific NOTCH1 antibody we demonstrate that FIH-mediated NICD1 hydroxylation is reduced upon hypoxia or treatment with the hydroxylase inhibitor dimethyloxalylglycine (DMOG). We find that a hydroxylation-resistant NICD1 mutant is functionally impaired and more ubiquitinated. Interestingly, we also observe that the NICD1-deubiquitinating enzyme USP10 is downregulated upon hypoxia. Moreover, the interaction between the hydroxylation-defective NICD1 mutant and USP10 is significantly reduced compared to the NICD1 wild-type counterpart. Together, our data suggest that FIH hydroxylates NICD1 in normoxic conditions, leading to the recruitment of USP10 and subsequent NICD1 deubiquitination and stabilization. In hypoxia, this regulatory loop is disrupted, causing a dampened Notch response.