Our Collective Tensions:Paradox Research Community’s Response to COVID-19

In this commentary on three articles from dozens of paradox theory scholars on paradox approaches to examining the COVID-19 pandemic and how the COVID-19 pandemic informs paradox theory, the authors involved in coordinating the collection of three papers discuss the process of bringing together scholars from around the world to discuss the pandemic. Four other preeminent paradox theorists offer additional commentaries on the papers in this Collection.</p

The Mass of the Black Hole in the Seyfert 1 Galaxy NGC 4593 from Reverberation Mapping

We present new observations leading to an improved black hole mass estimate for the Seyfert 1 galaxy NGC 4593 as part of a reverberation-mapping campaign conducted at the MDM Observatory. Cross-correlation analysis of the H_beta emission-line light curve with the optical continuum light curve reveals an emission-line time delay of 3.73 (+-0.75) days. By combining this time delay with the H_beta line width, we derive a central black hole mass of M_BH = 9.8(+-2.1)x10^6 M_sun, an improvement in precision of a factor of several over past results.Comment: 22 pages, 3 tables, 5 figures, accepted for publication in Ap

Diverging and Converging: Integrative Insights on a Paradox Meta-perspective

Paradox theory stands at an exciting moment in organization and management theory. Scholars increasingly seek out insights about the nature and management of contradictory demands to explain a wide array of organizational phenomena across multiple levels of analysis. Our two reviews in the 2016 Academy of Management Annals attest to this growing breadth and depth, each integrating and expanding related, yet different bodies of research. Schad, Lewis, Raisch, and Smith (2016) emphasize the depth of scholarship by analyzing an increasing number of paradox studies within management science. Putnam, Fairhurst, and Banghart (2016) highlight the breadth of scholarship by comparing paradoxes that emerge from multiple theories and paradigms that embrace an interdisciplinary orientation. By drawing on distinct literatures, these two manuscripts reveal diverse insights and reflections about paradoxical demands in organizations. In this integrative reflection, we juxtapose our two review articles, surface distinct assumptions and emphases, highlight complementarities, and raise questions for future scholarship. In doing so, we hope to fuel insights toward a meta-perspective on paradox

Ambidextrie – der organisationale Drahtseilakt. Synergie zwischen Exploration und Exploitation als Voraussetzung für die digitale Transformation

Sich disruptiv verändernde Rahmenbedingungen können dazu führen, dass bisher erfolgreiche Geschäftsmodelle innert weniger Jahren obsolet werden. Geschuldet ist dies einer mangelnden Anpassungsfähigkeit, deren Ursache unter anderem in der sogenannten Pfadabhängigkeit wurzeln kann. Die Pfadabhängigkeit bezeichnet eine Situation, in der die Auswirkungen von stark durch die Vergangenheit geprägten Entscheiden dazu führen, dass die Möglichkeit bzw. Notwendigkeit neuer Geschäftsmodelle nicht erkannt, verpasst oder deren Chancen falsch eingeschätzt werden. Das Ausbrechen aus der Pfadabhängigkeit ist für den Fortbestand von Unternehmen daher von zentraler Bedeutung. Das Konzept der organisationalen Ambidextrie widmet sich dieser Problemstellung. Ambidextrie beschreibt die Fähigkeit eines Unternehmens, einerseits das Kerngeschäft stetig weiterzuentwickeln, gleichzeitig aber auch neue Wege und Denkweisen zu etablieren und so sicherzustellen, dass Veränderungen im Umsystem rechtzeitig erkannt und die sich dadurch bietenden Chancen für die Zukunft genutzt werden. Eine Fähigkeit, die gerade im Zeitalter der Digitalisierung an Wichtigkeit gewinnt

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07

C. elegans Agrin Is Expressed in Pharynx, IL1 Neurons and Distal Tip Cells and Does Not Genetically Interact with Genes Involved in Synaptogenesis or Muscle Function

Agrin is a basement membrane protein crucial for development and maintenance of the neuromuscular junction in vertebrates. The C. elegans genome harbors a putative agrin gene agr-1. We have cloned the corresponding cDNA to determine the primary structure of the protein and expressed its recombinant fragments to raise specific antibodies. The domain organization of AGR-1 is very similar to the vertebrate orthologues. C. elegans agrin contains a signal sequence for secretion, seven follistatin domains, three EGF-like repeats and two laminin G domains. AGR-1 loss of function mutants did not exhibit any overt phenotypes and did not acquire resistance to the acetylcholine receptor agonist levamisole. Furthermore, crossing them with various mutants for components of the dystrophin-glycoprotein complex with impaired muscle function did not lead to an aggravation of the phenotypes. Promoter-GFP translational fusion as well as immunostaining of worms revealed expression of agrin in buccal epithelium and the protein deposition in the basal lamina of the pharynx. Furthermore, dorsal and ventral IL1 head neurons and distal tip cells of the gonad arms are sources of agrin production, but no expression was detectable in body muscles or in the motoneurons innervating them. Recombinant worm AGR-1 fragment is able to cluster vertebrate dystroglycan in cultured cells, implying a conservation of this interaction, but since neither of these proteins is expressed in muscle of C. elegans, this interaction may be required in different tissues. The connections between muscle cells and the basement membrane, as well as neuromuscular junctions, are structurally distinct between vertebrates and nematodes

Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity

Hair Cortisol in Twins : Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes

A. Palotie on työryhmän jäsen.Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.Peer reviewe

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways