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Slack is a prominent construct in management research, and has been shown to be relevant for a wide range of phenomena. Yet, despite slack's prominence and breadth of application, our review reveals a lack of clarity and consistency in the categorization, theorizing, and measurement of various types and forms of slack. This has led to differences in the characterization and treatment of seemingly identical kinds of slack, which prevents full exploitation of the conceptual depth of the slack construct and thus the creation of robust knowledge about slack resources. Based on a review of 229 studies that explicitly theorized about slack, we identify two fundamental dimensions of the slack construct—availability and fungibility—that allow us to: (a) systematize and integrate past research about slack and its implications for organizations, (b) enrich and expand theorizing on slack by advancing a novel typology for understanding slack resourcing decisions and orchestration in organizations, and (c) reinvigorate and open newdirections for future research on slack. [ABSTRACT FROM AUTHOR]

Both upper echelons theory and the behavioral theory of the firm (BTOF) have made important contributions to our understanding of the drivers of managerial risk-taking. Yet, how the individual- and organizational-level mechanisms espoused by these theories act in concert to determine risk-taking is not well understood. In this paper, we draw on regulatory focus theory as a fulcrum to bridge these two levels of analyses and integrate insights from both theoretical traditions. Consistent with the BTOF, we argue that promotion-focused CEOs engage in increased (decreased) risk-taking under conditions of performance below (above) aspirations. In contrast to the predictions of the BTOF, however, we predict that prevention-focused CEOs engage in increased (decreased) risk-taking under conditions of performance above (below) aspirations. We find support for these arguments in a large sample of CEOs from publicly listed U.S. firms and discuss the implications of our findings for both theory and practice. [ABSTRACT FROM AUTHOR]

The mechanisms underlying dopamine neuron loss in Parkinson's disease (PD) are not clearly defined. Here, we delineate a pathway by which dopaminergic loss induced by 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP) is controlled in vivo. We reported previously that calpains play a central required role in dopamine loss after MPT Ptreatment. Here, we provide evidence that the downstream effector pathway of calpains is through cyclin-dependent kinase 5 (cdk5)-mediated modulation of the transcription factor myocyte enhancer factor 2 (MEF2). We show that MPTP-induced conversion of the cdk5 activator p35 to a pathogenic p25 form is dependent on calpain activity in vivo. In addition, p35 deficiency attenuates MPTP-induced dopamine neuron loss and behavioral outcome. Moreover, MEF2 is phosphorylated on Ser444, an inactivating site, after MPTP treatment. This phosphorylation is dependent on both calpain and p35 activity, consistent with the model that calpain-mediated activation of cdk5 results in phosphorylation of MEF2 in vivo. Finally, we provide evidence that MEF2 is critical for dopaminergic loss because "cdk5 phosphorylation site mutant" of MEF2D provides neuroprotection in an MPTP mouse model of PD. Together, these data indicate that calpain-p35-p25/cdk5-mediated inactivation of MEF2 plays a critical role in dopaminergic loss in vivo. [ABSTRACT FROM AUTHOR]

Growing evidence implicates microglia in the loss of dopaminergic neurons in Parkinson's disease (PD). However, factors mediating microglial activation in PD are poorly understood. Proinflammatory cytokines, such as interferon-gamma (IFN-gamma), orchestrate the actions of microglia. We report here that PD patients express significantly elevated levels of IFN-gamma in their blood plasma. After this initial finding, we found that IFN-gamma-deficient mice displayed attenuated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced substantia nigra pars compacta dopaminergic cell loss along with reduced loss of striatal tyrosine hydroxylase and dopamine transporter fiber density. MPTP-induced depletion of striatal dopamine and its metabolite DOPAC (3,4-dihydroxyphenylacetic acid), as well as deltaFosB, a marker of postsynaptic dysfunction, were also attenuated in these knock-out mice. Consistent with the role for IFN-gamma in microglial activation, MPTP-induced morphological activation of microglia was abrogated compared with wild-type mice. To examine more mechanistically the role of IFN-gamma in microglial activation, we evaluated the interactions between microglia and dopaminergic neurons in an in vitro mixed microglia/midbrain neuron rotenone-induced death paradigm. In this in vitro paradigm, dopaminergic neurons are selectively damaged by rotenone. Exogenous IFN-gamma ligand alone and without rotenone resulted in dopaminergic cell loss, but only in the presence of microglia. The addition of an IFN-gamma neutralizing antibody attenuated neuronal loss as a result of rotenone treatment. The presence of only wild-type microglia and not those deficient in IFN-gamma receptor elicited significant dopaminergic cell loss when exposed to rotenone. Neurons deficient in IFN-gamma receptor, however, did not display increased resistance to death. Finally, levels of IFN-gamma message increased in microglia in response to rotenone. Together, these data suggest that IFN-gamma participates in death of dopaminergic neurons by regulating microglial activity.