Nietzsche as a Critic of Genealogical Debunking: Making Room for Naturalism without Subversion

This paper argues that Nietzsche is a critic of just the kind of genealogical debunking he is popularly associated with. We begin by showing that interpretations of Nietzsche which see him as engaging in genealogical debunking turn him into an advocate of nihilism, for on his own premises, any truthful genealogical inquiry into our values is going to uncover what most of his contemporaries deem objectionable origins and thus license global genealogical debunking. To escape nihilism and make room for naturalism without indiscriminate subversion, we then argue, Nietzsche targets the way of thinking about values that permits genealogical debunking: far from trying to subvert values simply by uncovering their origins, Nietzsche is actively criticising genealogical debunking thus understood. Finally, we draw out the consequences of our reading for Nietzsche’s positive vision

What is an Award Worth? An Econometric Assessment of the Impact of Awards on Employee Performance

Behavioral economics documents the importance of status and self-image concerns in the workplace, but is largely silent about how to instrumentalize them to induce effort. Awards - widespread in the corporate sector and elsewhere - are motivators that derive their value from such social concerns. Panel data from the call center of a large international bank allow us to estimate the impact of receiving an award on effort. The performance of winners proves to be significantly higher than that of comparable non-recipients after the award has been presented. This increase in work effort is sizeable, robust, and not driven by reverse causation.awards, motivation, non-monetary compensation, event-study, incentives

Why Invest In Art?

In recent years, the art market experienced a price explosion for paintings. Frey and Cueni shed light on the reasons for the price increase, on the rate of return in the art market, on the emergence and decline of art hedge funds, and on the risks of art investment

Awards at work

Social incentives like employee awards are widespread in the corporate sector and may be important instruments for solving agency problems. To date, we have little understanding of their effect on behavior. Unique panel data from the call center of a Fortune 500 financial services provider allow us to estimate the impact of awards on performance. Winning an award for voluntary work behaviors significantly increases subsequent core call center performance. The effect is short-lived, mainly driven by underperforming agents, and is reflected mostly in dimensions of the job that are hard to observe. We discuss various theories that could explain the effect

Ca2+ signaling by T-type Ca2+ channels in neurons

Among the major families of voltage-gated Ca2+ channels, the low-voltage-activated channels formed by the Cav3 subunits, referred to as T-type Ca2+ channels, have recently gained increased interest in terms of the intracellular Ca2+ signals generated upon their activation. Here, we provide an overview of recent reports documenting that T-type Ca2+ channels act as an important Ca2+ source in a wide range of neuronal cell types. The work is focused on T-type Ca2+ channels in neurons, but refers to non-neuronal cells in cases where exemplary functions for Ca2+ entering through T-type Ca2+ channels have been described. Notably, Ca2+ influx through T-type Ca2+ channels is the predominant Ca2+ source in several neuronal cell types and carries out specific signaling roles. We also emphasize that Ca2+ signaling through T-type Ca2+ channels occurs often in select subcellular compartments, is mediated through strategically co-localized targets, and is exploited for unique physiological function

What is an award worth? : an econometric assessment of the impact of awards on employee performance

Behavioral economics documents the importance of status and self-image concerns in the workplace, but is largely silent about how to instrumentalize them to induce effort. Awards - widespread in the corporate sector and elsewhere - are motivators that derive their value from such social concerns. Panel data from the call center of a large international bank allow us to estimate the impact of receiving an award on effort. The performance of winners proves to be significantly higher than that of comparable non-recipients after the award has been presented. This increase in work effort is sizeable, robust, and not driven by reverse causation

Replication of segment-specific and intercalated cells in the mouse renal collecting system

The renal collecting system (CS) is composed of segment-specific (SS) and intercalated (IC) cells. The latter comprise at least two subtypes (type A and non-type A IC). The origin and maintenance of cellular heterogeneity in the CS is unclear. Among other hypotheses, it was proposed that one subtype of IC cells represents a stem cell population from which all cell types in the CS may arise. In the present study, we tested this stem cell hypothesis for the adult kidney by assessing DNA synthesis as a marker for cell replication. SS and IC cells were identified by their characteristic expressions of sodium- (epithelial sodium channel, Na-K-ATPase), water- (aquaporin-2) and acid/base- (H+-ATPase, anion exchanger AE1) transporting proteins. Immunostaining for bromodeoxyuridine (BrdU) and for the proliferating cell nuclear antigen (PCNA) was used to reveal DNA synthesis in CS epithelium. BrdU- and PCNA-immunostaining as well as mitotic figures were seen in all subtypes of CS cells. Dividing cells retained the cell-type specific expression of marker molecules. Treatment of mice with bumetanide combined with a high oral salt intake, which increases the tubular salt load in the CS, profoundly increased the DNA-synthesis rate in SS and non-type A IC cells, but reduced it in type A IC cells. Thus, our data show that DNA synthesis and cell replication occur in each cell lineage of the CS and in differentiated cells. The replication rate in each cell type can be differently modulated by functional stimulation. Independent proliferation of each cell lineage might contribute to maintain the cellular heterogeneity of the CS of the adult kidney and may also add to the adaptation of the CS to altered functional requirement

Immunofluorescent localization of the Rab-GAP protein TBC1D4 (AS160) in mouse kidney

TBC1D4 (or AS160) was identified as a Rab-GTPase activating protein (Rab-GAP) that controls insulin-dependent trafficking of the glucose transporter GLUT4 in skeletal muscle cells and in adipocytes. Recent in vitro cell culture studies suggest that TBC1D4 may also regulate the intracellular trafficking of kidney proteins such as the vasopressin-dependent water channel AQP2, the aldosterone-regulated epithelial sodium channel ENaC, and the Na+-K+-ATPase. To study the possible role of TBC1D4 in the kidney in vivo, we raised a rabbit polyclonal antibody against TBC1D4 to be used for immunoblotting and immunohistochemical studies. In immunoblots on mouse kidney homogenates, the antibody recognizes specific bands at the expected size of 160kDa and at lower molecular weights, which are absent in kidneys of TBC1D4 deficient mice. Using a variety of nephron-segment-specific marker proteins, immunohistochemistry reveals TBC1D4 in the cytoplasm of the parietal epithelial cells of Bowman's capsule, the thin and thick limbs of Henle's loop, the distal convoluted tubule, the connecting tubule, and the collecting duct. In the latter, both principal as well as intercalated cells are TBC1D4-positive. Thus, with the exception of the proximal tubule, TBC1D4 is highly expressed along the nephron and the collecting duct, where it may interfere with the intracellular trafficking of many renal transport proteins including AQP2, ENaC and Na+-K+-ATPase. Hence, TBC1D4 may play an important role for the control of renal ion and water handling and hence for the control of extracellular fluid homeostasi

Characterization of renal interstitial fibroblast-specific protein1/S100A4-positive cells in healthy and inflamed rodent kidneys

Fibrosis is considered as a central factor in the loss of renal function in chronic kidney diseases. The origin of fibroblasts and myofibroblasts that accumulate in the interstitium of the diseased kidney is still a matter of debate. It has been shown that accumulation of myofibroblasts in inflamed and fibrotic kidneys is associated with upregulation of fibroblast-specific protein1 (FSP1, S100A4), not only in the renal interstitium but also in the injured renal epithelia. The tubular expression of FSP1 has been taken as evidence of myofibroblast formation by epithelial-mesenchymal transition (EMT). The identity of FSP1/S100A4 cells has not been defined in detail. We originally intended to use FSP1/S100A4 as a marker of putative EMT in a model of distal tubular injury. However, since the immunoreactivity of FSP1 did not seem to fit with the distribution and shape of fibroblasts or myofibroblasts, we undertook the characterization of FSP1/S100A4-expressing cells in the interstitium of rodent kidneys. We performed immunolabeling for FSP1/S100A4 on thin cryostat sections of perfusion-fixed rat and mouse kidneys with peritubular inflammation, induced by thiazides and glomerulonephritis, respectively, in combination with ecto-5′-nucleotidase (5′NT), recognizing local cortical peritubular fibroblasts, with CD45, MHC classII, CD3, CD4 and Thy1, recognizing mononuclear cells, with alpha smooth muscle actin (αSMA), as marker for myofibroblasts, and vimentin for intracellular intermediate filaments in cells of mesenchymal origin. In the healthy interstitium of rodents the rare FSP1/S100A4+ cells consistently co-expressed CD45 or lymphocyte surface molecules. Around the injured distal tubules of rats treated for 3-4 days with thiazides, FSP1+/S100A4+, 5′NT+, αSMA+, CD45+ and MHC classII+ cells accumulated. FSP1+/S100A4+ cells consistently co-expressed CD45. In the inflamed regions, αSMA was co-expressed by 5′NT+ cells. In glomerulonephritic mice, FSP1+/S100A4+ cells co-expressed Thy1, CD4 or CD3. Thus, in the inflamed interstitium around distal tubules of rats and of glomerulonephritic mice, the majority of FSP1+ cells express markers of mononuclear cells. Consequently, the usefulness of FSP1/S100A4 as a tool for detection of (myo)fibroblasts in inflamed kidneys and of EMT in vivo is put into question. In the given rat model the consistent co-expression of αSMA and 5′NT suggests that myofibroblasts originate from resident peritubular fibroblast

Aldosterone deficiency adversely affects pregnancy outcome in mice

Circulating aldosterone levels are increased in human pregnancy. Inadequately low aldosterone levels as present in preeclampsia, a life-threatening disease for both mother and child, are discussed to be involved in its pathogenesis or severity. Moreover, inactivating polymorphisms in the aldosterone synthase gene have been detected in preeclamptic women. Here, we used aldosterone synthase-deficient (AS−/−) mice to test whether the absence of aldosterone is sufficient to impair pregnancy or even to cause preeclampsia. AS−/− and AS+/+ females were mated with AS+/+ and AS−/− males, respectively, always generating AS+/− offspring. With maternal aldosterone deficiency in AS−/− mice, systolic blood pressure was low before and further reduced during pregnancy with no increase in proteinuria. Yet, AS−/− had smaller litters due to loss of fetuses as indicated by a high number of necrotic placentas with massive lymphocyte infiltrations at gestational day 18. Surviving fetuses and their placentas from AS−/− females were smaller. High-salt diet before and during pregnancy increased systolic blood pressure only before pregnancy in both genotypes and abolished the difference in blood pressure during late pregnancy. Litter size from AS−/− was slightly improved and the differences in placental and fetal weights between AS+/+ and AS−/− mothers disappeared. Overall, an increased placental efficiency was observed in both groups paralleled by a normalization of elevated HIF1α levels in the AS−/− placentas. Our results demonstrate that aldosterone deficiency has profound adverse effects on placental function. High dietary salt intake improved placental function. In this animal model, aldosterone deficiency did not cause preeclampsi