α2 Integrin-Dependent Suppression of Pancreatic Adenocarcinoma Cell Invasion Involves Ectodomain Regulation of Kallikrein-Related Peptidase-5

Previous reports demonstrate that the α2-integrin (α2) mediates pancreatic ductal adenocarcinoma (PDAC) cell interactions with collagens. We found that while well-differentiated cells use α2 exclusively to adhere and migrate on collagenI, poorly differentiated PDAC cells demonstrate reduced reliance on, or complete loss of, α2. Since well-differentiated PDAC lines exhibit reduced in vitro invasion and α2-blockade suppressed invasion of well-differentiated lines exclusively, we hypothesized that α2 may suppress the malignant phenotype in PDAC. Accordingly, ectopic expression of α2 retarded in vitro invasion and maintenance on collagenI exacerbated this effect. Affymetrix profiling revealed that kallikrein-related peptidase-5 (KLK5) was specifically upregulated by α2, and reduced α2 and KLK5 expression was observed in poorly differentiated PDAC cells in situ. Accordingly, well-differentiated PDAC lines express KLK5, and KLK5 blockade increased the invasion of KLK5-positive lines. The α2-cytoplasmic domain was dispensable for these effects, demonstrating that the α2-ectodomain and KLK5 coordinately regulate a less invasive phenotype in PDAC

CFO Promotion-based Incentives and Earnings Management

This study examines whether CFO promotion-based incentives induce opportunistic reporting activities. We find that CFO promotion-based incentives, measured by the pay gap between the CEO and the CFO, are positively associated with accruals management and accounting misconduct in the pre-SOX period and the probability of meeting or beating analysts’ forecasts in both the pre- and post-SOX periods. Further analysis shows that CFO promotion-based incentives are negatively associated with real earnings management in both the pre- and post-SOX periods. In addition, we find some evidence that the association between CFO promotion-based incentives and opportunistic reporting activities is stronger before CEO turnovers. We also document that CFOs engage in more opportunistic financial reporting when the pay gap between the CFO and other VPs is greater. Overall, our findings suggest that CFO promotion-based incentives may encourage CFOs to engage in opportunistic reporting activities but mitigate real earnings management

Where is the Line? The Effect of Narrowed Scope of Discontinued Operations on Earnings Quality and Analysts’ Forecasts

In the past decades, the U.S. accounting standards have been trending toward more narrowed scope for the “below-the-line” items. This study examines whether the quality of “above-the-line” (or core) earnings and analysts’ forecasts is affected by the recent major rule change in this regard (i.e., ASU2014-8), which imposes much more stringent criteria for classifying dispositions as below-the-line items (i.e., discontinued operations). Using data surrounding this rule change, we find that the frequency of reported discontinued operations significantly reduces after the change, suggesting underlying dispositions being buried in the core earnings. More importantly, we find that the persistence and response coefficient of core earnings significantly reduce and that analysts’ forecast error and dispersion increase. Thus, the narrowed scope of below-the-line items required by ASU 2014-8 introduces significant noise to core earnings and increases information asymmetry and uncertainty between managers and financial analysts. Our findings should be of interest to accounting regulators, firm managers, analysts, and investors when they interpret both above- and below-the-line items

Morphine-induced Suppression of Conditioned Stimulus Intake: Effects of Stimulus Type and Insular Cortex Lesions

Intake of an unconditionally preferred taste stimulus (e.g., saccharin) is reduced by contingent administration of a drug of abuse (e.g., morphine). We examined the influence of insular cortex (IC) lesions on morphine-induced suppression of an olfactory cue and two taste stimuli with different levels of perceived innate reward value. Two major findings emerged from this study. First, morphine suppressed intake of an aqueous odor as well as each taste stimulus in neurologically intact rats. Second, IC lesions disrupted morphine-induced suppression of the taste stimuli but not the aqueous odor cue. These results indicate that the perceived innate reward value of the CS is not a factor that governs drug-induced intake suppression

Insular Cortex and Consummatory Successive Negative Contrast in the Rat

Rats that are expecting a high value reward (e.g., 1.0 M sucrose) show an exaggerated underresponding when they are instead given a low value reward (e.g., 0.15% saccharin), an effect termed successive negative contrast (SNC). In the present experiment, insular cortex-lesioned (ICX) rats showed normal responsivity to sucrose and saccharin prior to the reward downshift. However, when switched from sucrose to saccharin during the postshift trials these rats displayed no evidence of SNC. Indeed, over the downshift trials these ICX rats consistently drank more saccharin than the ICX rats maintained on saccharin throughout the experiment. Potential interpretations are discussed including a lesion-induced impairment in the ability to accurately recognize the novelty of the postshift saccharin stimulus

Conditioned Taste Aversion and Latent Inhibition Following Extensive Taste Preexposure in Rats with Insular Cortex Lesions

Lesions of the insular cortex (IC) attenuate acquisition of conditioned taste aversions (CTAs). We have suggested that this impairment is the expected consequence of a failure of IC-lesioned (ICX) rats to recognize unfamiliar taste stimuli as novel. That is, ICX rats treat novel taste stimuli as if they are familiar and as a result show a latent inhibition-like retardation of learning. This account anticipates that ICX rats should acquire CTAs at the same slow rate as normal rats that are familiar with the taste stimulus. The present experiment confirmed this hypothesis in a design that compared CTA acquisition in normal and ICX rats following either extensive taste familiarization or no taste familiarization prior to conditioning

Taste-Potentiated Odor Aversion Learning in Rats with Lesions of the Insular Cortex

The current study assessed the influence of excitotoxic lesions of the insular cortex (IC) on tastepotentiated odor aversion (TPOA) learning. Water-deprived rats initially received a single odortoxicosis or odor/taste-toxicosis pairing and were subsequently tested, in separate trials, with the odor and the taste stimulus. Indicating TPOA, neurologically intact rats conditioned with the odor/taste compound stimulus acquired significantly stronger odor aversions than normal rats conditioned with the odor stimulus. IC lesions disrupted TPOA, conditioned taste aversion and taste neophobia. The finding that taste did not potentiate odor aversion learning in the IC lesioned rats provides support for the “within-compound association” analysis but is inconsistent with the “sensory and-gate” account of TPOA learning