Leistungsorientierte Vergütung in Nonprofit-Organisationen? Weiterführende Diskussion des Artikels von Brandl et al. zur Entwicklungsdynamik von Vergütungssystemen in Nonprofit-Organisationen.

Der wertvolle Beitrag von Brandl et al. beschäftigt sich mit der Entwicklungsdynamik von Vergütungssystemen in Nonprofit-Organisationen (NPO). Die Autoren stellen sich die Frage, 'weshalb es zu Veränderungen von Vergütungssystemen für gehobene Fach- und Führungskräfte in Nonprofit-Organisationen kommt (Entwicklungslogik) und welcher Dynamik deren Entwicklung folgt' (S. 344). Sie zeigen einen Trend von einem personenzentrierten zu einem funktionszentrierten zu einem leistungszentrierten Vergütungssystem auf, stellen aber fest, dass NPO auf das letztgenannte Konzept eher ablehnend reagieren. Die Gründe dafür vermuten sie unseres Erachtens zurecht unter anderem in der Kultur und der Entwicklungsdynamik dieser Organisationen. Am Ende des Beitrags werden drei weiterführende Forschungsarbeiten aufgezeigt; zwei davon möchten wir in unserer Diskussion aufgreifen. Sinngemäß ließen sich mit Bezug auf Brandl et al. zwei Forschungsfragen formulieren: (a) Wie wirken sich Elemente variabler Vergütungen auf die Identität der NPO aus? (b) Welcher Zusammenhang besteht zwischen Veränderungen der Organisation und der Neugestaltung von Vergütungssystemen (vgl. S. 359)

Adorno?s Grey, Taussig?s Blue: Colour, Organization and Critical Affect

In this article we seek to open up the study of affect and organization to colour. Often simply taken for granted in organizational life and usually neglected in organizational thought, colour is an affective force by default. Deploying and interweaving the languages of affect theory, critical theory, and organization studies, we discuss colour as a primary phenomenon for the study of ?critical affect?. We then trace colour?s affect in conditioning the unfolding of organization in two particular ?colour/spaces? ? Adorno?s grey and Taussig?s blue of our title ? and discuss both its ambiguity and critical potential. Finally, we ponder what colour might do to the style of an organizational scholarship attuned to affect, where sentences blur with things and forces more than they seek to represent them

Organize

Digital media technologies re-pose the question of organization - and thus of power and domination, control and surveillance, disruption and emancipation. This book interrogates organization as effect and condition of media. How can we understand the recursive relationship between media and organization? How can we think, explore, critique - and perhaps alter - the organizational bodies and scripts that shape contemporary life

Who’s afraid of the senses? Organization, management and the return of the sensorium

Organization and management are the perpetual, and perpetually fraught and resisted, ordering of sense experience. However, banning the senses into the outside of thought, and of organizational analysis, was – and to a large degree still is – the default and mostly implicit and unquestioned mode of thinking and studying organization and management. Introducing the special issue on ‘The Senses in Management Research and Education’, this essay historicizes and contextualizes the neglect of the senses, dwells upon possible reasons for keeping the sensory at bay and discusses recent attempts to remedy this situation. The contributions to the special issue are introduced into this context. In conclusion, we speculate on what might happen next

Oncogenic enhancers prime quiescent metastatic cells to escape NK immune surveillance by eliciting transcriptional memory

Metastasis arises from disseminated tumour cells (DTCs) that are characterized by intrinsic phenotypic plasticity and the capability of seeding to secondary organs. DTCs can remain latent for years before giving rise to symptomatic overt metastasis. In this context, DTCs fluctuate between a quiescent and proliferative state in response to systemic and microenvironmental signals including immune-mediated surveillance. Despite its relevance, how intrinsic mechanisms sustain DTCs plasticity has not been addressed. By interrogating the epigenetic state of metastatic cells, we find that tumour progression is coupled with the activation of oncogenic enhancers that are organized in variable interconnected chromatin domains. This spatial chromatin context leads to the activation of a robust transcriptional response upon repeated exposure to retinoic acid (RA). We show that this adaptive mechanism sustains the quiescence of DTCs through the activation of the master regulator SOX9. Finally, we determine that RA-stimulated transcriptional memory increases the fitness of metastatic cells by supporting the escape of quiescent DTCs from NK-mediated immune surveillance. Overall, these findings highlight the contribution of oncogenic enhancers in establishing transcriptional memories as an adaptive mechanism to reinforce cancer dormancy and immune escape, thus amenable for therapeutic intervention.Acknowledgements: We thank the NGS facility from CIBIO for their help with EU-RNA-seq, ATAC-seq, and CUT&RUN sequencing; the imaging facility from CIBIO for SIM microscopy; the Cell Analysis and Separation facility from CIBIO for cell sorting and FACS analyses; the High Throughput Screening facility from CIBIO for the acquisition of tumor sections. We would like to thank the members of the Tiberi and Zippo labs for helpful discussion and critical reading of the manuscript. We thank the Cusanelli lab for supporting us with the smRNA-FISH methodology. We thank Dr. Ron Vale for sharing the pHRdSV40-dCas9-10xGCN4_v4-P2A-BFP construct, Dr. Sakari Vanharanta for sharing the pKLV-U6gRNA(BbsI)-PGKpuro2A-BFP construct, Dr. Kenneth S. Zaret for TOPO spike-in plasmids and Dr. Federica Facciotti for sharing the NK-92 cell line. Work in the Zippo group was supported by grants from the AIRC foundation (IG 2019- 22911) and European Union under the Horizon 2020 Framework Pro[1]gramme H2020 Future and Emerging Technologies (801336; - PRO-CHIP). Work in the Todaro group was supported by grants from the AIRC foundation (IG 2018—ID. 21492). S. Beyes was supported by the Deutsche Forschungsgemeinschaft (DFG—BE 7359/1-1). V. Poli and S. Lago were recipients of AIRC fellowships (21158 and 25373)

EGFR-targeted TRAIL and a Smac mimetic synergize to overcome apoptosis resistance in KRAS mutant colorectal cancer cells

TRAIL is a death receptor ligand that induces cell death preferentially in tumor cells. Recombinant soluble TRAIL, however, performs poorly as an anti-cancer therapeutic because oligomerization is required for potent biological activity. We previously generated a diabody format of tumor-targeted TRAIL termed DbαEGFR-scTRAIL, comprising single-stranded TRAIL molecules (scTRAIL) and the variable domains of a humanized variant of the EGFR blocking antibody Cetuximab. Here we define the bioactivity of DbαEGFR-scTRAIL with regard to both EGFR inhibition and TRAIL receptor activation in 3D cultures of Caco-2 colorectal cancer cells, which express wild-type K-Ras. Compared with conventional 2D cultures, Caco-2 cells displayed strongly enhanced sensitivity toward DbαEGFR-scTRAIL in these 3D cultures. We show that the antibody moiety of DbαEGFR-scTRAIL not only efficiently competed with ligand-induced EGFR function, but also determined the apoptotic response by specifically directing DbαEGFR-scTRAIL to EGFR-positive cells. To address how aberrantly activated K-Ras, which leads to Cetuximab resistance, affects DbαEGFR-scTRAIL sensitivity, we generated stable Caco-2tet cells inducibly expressing oncogenic K-RasG12V. In the presence of doxycycline, these cells showed increased resistance to DbαEGFR-scTRAIL, associated with the elevated expression of the anti-apoptotic proteins cIAP2, Bcl-xL and FlipS. Co-treatment of cells with the Smac mimetic SM83 restored the DbαEGFR-scTRAIL-induced apoptotic response. Importantly, this synergy between DbαEGFR-scTRAIL and SM83 also translated to 3D cultures of oncogenic K-Ras expressing HCT-116 and LoVo colorectal cancer cells. Our findings thus support the notion that DbαEGFR-scTRAIL therapy in combination with apoptosis-sensitizing agents may be promising for the treatment of EGFR-positive colorectal cancers, independently of their KRAS status

Effective targeting of breast cancer stem cells by combined inhibition of Sam68 and Rad51

: Breast cancer (BC) is the second cause of cancer-related deceases in the worldwide female population. Despite the successful treatment advances, 25% of BC develops resistance to current therapeutic regimens, thereby remaining a major hurdle for patient management. Current therapies, targeting the molecular events underpinning the adaptive resistance, still require effort to improve BC treatment. Using BC sphere cells (BCSphCs) as a model, here we showed that BC stem-like cells express high levels of Myc, which requires the presence of the multifunctional DNA/RNA binding protein Sam68 for the DNA-damage repair. Analysis of a cohort of BC patients displayed that Sam68 is an independent negative factor correlated with the progression of the disease. Genetic inhibition of Sam68 caused a defect in PARP-induced PAR chain synthesis upon DNA-damaging insults, resulting in cell death of TNBC cells. In contrast, BC stem-like cells were able to survive due to an upregulation of Rad51. Importantly, the inhibition of Rad51 showed synthetic lethal effect with the silencing of Sam68, hampering the cell viability of patient-derived BCSphCs and stabilizing the growth of tumor xenografts, including those TNBC carrying BRCA mutation. Moreover, the analysis of Myc, Sam68 and Rad51 expression demarcated a signature of a poor outcome in a large cohort of BC patients. Thus, our findings suggest the importance of targeting Sam68-PARP1 axis and Rad51 as potential therapeutic candidates to counteract the expansion of BC cells with an aggressive phenotype

Oncogenic enhancers prime quiescent metastatic cells to escape NK immune surveillance by eliciting transcriptional memory

Metastasis arises from disseminated tumour cells (DTCs) that are characterized by intrinsic phenotypic plasticity and the capability of seeding to secondary organs. DTCs can remain latent for years before giving rise to symptomatic overt metastasis. In this context, DTCs fluctuate between a quiescent and proliferative state in response to systemic and microenvironmental signals including immune-mediated surveillance. Despite its relevance, how intrinsic mechanisms sustain DTCs plasticity has not been addressed. By interrogating the epigenetic state of metastatic cells, we find that tumour progression is coupled with the activation of oncogenic enhancers that are organized in variable interconnected chromatin domains. This spatial chromatin context leads to the activation of a robust transcriptional response upon repeated exposure to retinoic acid (RA). We show that this adaptive mechanism sustains the quiescence of DTCs through the activation of the master regulator SOX9. Finally, we determine that RA-stimulated transcriptional memory increases the fitness of metastatic cells by supporting the escape of quiescent DTCs from NK-mediated immune surveillance. Overall, these findings highlight the contribution of oncogenic enhancers in establishing transcriptional memories as an adaptive mechanism to reinforce cancer dormancy and immune escape, thus amenable for therapeutic intervention