The macrophage STING-YAP axis controls hepatic steatosis by promoting the autophagic degradation of lipid droplets.

BACKGROUND AND AIMS: The hallmark of NAFLD or hepatic steatosis is characterized by lipid droplet (LD) accumulation in hepatocytes. Autophagy may have profound effects on lipid metabolism and innate immune response. However, how innate immune activation may regulate the autophagic degradation of intracellular LDs remains elusive. APPROACH AND RESULTS: A mouse model of a high-fat diet-induced NASH was used in the myeloid-specific stimulator of interferon genes (STING) knockout or STING/yes-associated protein (YAP) double knockout mice. Liver injury, lipid accumulation, lipid droplet proteins, autophagic genes, chromatin immunoprecipitation coupled with massively parallel sequencing, and RNA-Seq were assessed in vivo and in vitro . We found that high-fat diet-induced oxidative stress activates STING and YAP pathways in hepatic macrophages. The acrophage STING deficiency (myeloid-specific STING knockout) enhances nuclear YAP activity, reduces lipid accumulation, and increases autophagy-related proteins ATG5, ATG7, and light chain 3B but diminishes LD protein perilipin 2 expression. However, disruption of STING and YAP (myeloid STING and YAP double knockout) increases serum alanine aminotransferase and triglyceride levels and reduces ß-fatty acid oxidation gene expression but augments perilipin 2 levels, exacerbating high-fat diet-induced lipid deposition. Chromatin immunoprecipitation coupled with massively parallel sequencing reveals that macrophage YAP targets transmembrane protein 205 and activates AMP-activated protein kinase α, which interacts with hepatocyte mitofusin 2 and induces protein disulfide isomerase activation. Protein disulfide isomerase activates hypoxia-inducible factor-1α signaling, increases autophagosome colocalization with LDs, and promotes the degradation of perilipin 2 by interacting with chaperone-mediated autophagy chaperone HSC70. CONCLUSIONS: The macrophage STING-YAP axis controls hepatic steatosis by reprogramming lipid metabolism in a transmembrane protein 205/mitofusin 2/protein disulfide isomerase-dependent pathway. These findings highlight the regulatory mechanism of the macrophage STING-driven YAP activity on lipid control.

The reputational and ethical consequences of deceptive chatbot use.

The use of chatbots is becoming widespread as they offer significant economic opportunities. At the same time, however, customers seem to prefer interacting with human operators when making inquiries and as a result are not as cooperative with chatbots when their use is known. This specific situation creates an incentive for organizations to use chatbots without disclosing this to customers. Will this deceptive practice harm the reputation of the organization, and the employees who work for them? Across four experimental studies, we demonstrate that prospective customers, who interact with an organization using chatbots, perceive the organization to be less ethical if the organization does not disclose the information about the chatbot to their customers (Study 1). Moreover, employees that work for an organization which requires them to facilitate the deceptive use of a chatbot exhibit greater turnover intentions (Study 2) and receive worse job opportunities from recruiters in both a hypothetical experimental setting (Study 3) and from professional job recruiters in the field (Study 4). These results highlight that using chatbots deceptively has far reaching negative effects, which begin with the organization and ultimately impact their customers and the employees that work for them.

No person is an island: Unpacking the work and after-work consequences of interacting with artificial intelligence.

The artificial intelligence (AI) revolution has arrived, as AI systems are increasingly being integrated across organizational functions into the work lives of employees. This coupling of employees and machines fundamentally alters the work-related interactions to which employees are accustomed, as employees find themselves increasingly interacting with, and relying on, AI systems instead of human coworkers. This increased coupling of employees and AI portends a shift toward more of an "asocial system," wherein people may feel socially disconnected at work. Drawing upon the social affiliation model, we develop a model delineating both adaptive and maladaptive consequences of this situation. Specifically, we theorize that the more employees interact with AI in the pursuit of work goals, the more they experience a need for social affiliation (adaptive)-which may contribute to more helping behavior toward coworkers at work-as well as a feeling of loneliness (maladaptive), which then further impair employee well-being after work (i.e., more insomnia and alcohol consumption). In addition, we submit that these effects should be especially pronounced among employees with higher levels of attachment anxiety. Results across four studies (N = 794) with mixed methodologies (i.e., survey study, field experiment, and simulation study; Studies 1-4) with employees from four different regions (i.e., Taiwan, Indonesia, United States, and Malaysia) generally support our hypotheses. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Novel role of macrophage TXNIP-mediated CYLD-NRF2-OASL1 axis in stress-induced liver inflammation and cell death.

Background & Aims: The stimulator of interferon genes (STING)/TANK-binding kinase 1 (TBK1) pathway is vital in mediating innate immune and inflammatory responses during oxidative/endoplasmic reticulum (ER) stress. However, it remains unknown whether macrophage thioredoxin-interacting protein (TXNIP) may regulate TBK1 function and cell death pathways during oxidative/ER stress. Methods: A mouse model of hepatic ischaemia/reperfusion injury (IRI), the primary hepatocytes, and bone marrow-derived macrophages were used in the myeloid-specific TXNIP knockout (TXNIPM-KO) and TXNIP-proficient (TXNIPFL/FL) mice. Results: The TXNIPM-KO mice were resistant to ischaemia/reperfusion (IR) stress-induced liver damage with reduced serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, macrophage/neutrophil infiltration, and pro-inflammatory mediators compared with the TXNIPFL/FL controls. IR stress increased TXNIP, p-STING, and p-TBK1 expression in ischaemic livers. However, TXNIPM-KO inhibited STING, TBK1, interferon regulatory factor 3 (IRF3), and NF-κB activation with interferon-ß (IFN-ß) expression. Interestingly, TXNIPM-KO augmented nuclear factor (erythroid-derived 2)-like 2 (NRF2) activity, increased antioxidant gene expression, and reduced macrophage reactive oxygen species (ROS) production and hepatic apoptosis/necroptosis in IR-stressed livers. Mechanistically, macrophage TXNIP deficiency promoted cylindromatosis (CYLD), which colocalised and interacted with NADPH oxidase 4 (NOX4) to enhance NRF2 activity by deubiquitinating NOX4. Disruption of macrophage NRF2 or its target gene 2',5' oligoadenylate synthetase-like 1 (OASL1) enhanced Ras GTPase-activating protein-binding protein 1 (G3BP1) and TBK1-mediated inflammatory response. Notably, macrophage OASL1 deficiency induced hepatocyte apoptotic peptidase activating factor 1 (APAF1), cytochrome c, and caspase-9 activation, leading to increased caspase-3-initiated apoptosis and receptor-interacting serine/threonine-protein kinase 3 (RIPK3)-mediated necroptosis. Conclusions: Macrophage TXNIP deficiency enhances CYLD activity and activates the NRF2-OASL1 signalling, controlling IR stress-induced liver injury. The target gene OASL1 regulated by NRF2 is crucial for modulating STING-mediated TBK1 activation and Apaf1/cytochrome c/caspase-9-triggered apoptotic/necroptotic cell death pathway. Our findings underscore a novel role of macrophage TXNIP-mediated CYLD-NRF2-OASL1 axis in stress-induced liver inflammation and cell death, implying the potential therapeutic targets in liver inflammatory diseases. Lay summary: Liver inflammation and injury induced by ischaemia and reperfusion (the absence of blood flow to the liver tissue followed by the resupply of blood) is a significant cause of hepatic dysfunction and failure following liver transplantation, resection, and haemorrhagic shock. Herein, we uncover an underlying mechanism that contributes to liver inflammation and cell death in this setting and could be a therapeutic target in stress-induced liver inflammatory injury.

A Case of Concurrent Disseminated Coccidioidomycosis and Embryonal Carcinoma When Lice and Fleas Coexist.

Coccidioidomycosis (CM) is a fungal infection endemic to the southwestern United States with a wide range of clinical presentations depending on the infected organ systems. Most infections are asymptomatic. Coccidioidomycosis causes a primary pulmonary infection and when symptoms occur, they most often resemble community-acquired pneumonia. One percent of cases disseminate, typically via hematogenous or lymphatic spread. It is in these cases that more severe symptoms may present and potentially overlap with those characteristics of other systemic illnesses. This is a case of CM disseminated to lymph nodes in a 24-year-old man with concomitant metastatic embryonal carcinoma. It is difficult to identify the primary etiology for many components of this patient's presentation, including diffuse lymphadenopathy and multiple pulmonary nodules. Furthermore, the relationship between these 2 concurrent disease processes is not entirely clear. Factors that may contribute include the well-known phenomenon of locus minoris resistentiae (LMR) or potentially a shared immune failure between infectious organisms and malignant cells.

ICU Interventions in Ischemic Stroke Patients Treated Using Liberalized IV-tPA Criteria.

BACKGROUND AND OBJECTIVE: Current standard practice guidelines recommend ICU admission for ischemic stroke patients treated with intravenous tissue plasminogen activator (IV-tPA). More recently, the trend in stroke care is to broaden eligibility for IV thrombolysis. Two examples are a more liberal inclusion criteria known as SMART criteria (sIV-tPA), and the transfer of patients to comprehensive stroke centers (CSC). The present study characterizes ICU interventions in these patients. Understanding which stroke patients that require ICU-level care may allow for placement of patients in the appropriate level of care at hospital admission. METHODS: We performed a retrospective review of consecutive transfer and nontransfer sIV-tPA-treated patients admitted to the ICU at a CSC. We evaluated the frequency, timing, and nature of ICU interventions. RESULTS: Three hundred and thirty one patients were treated with sIV-tPA and 42% required ICU interventions during ICU admission. Of patients requiring ICU interventions, 98% had an ICU intervention performed in triage, prior to admission. National Institute of Health Stroke Scale score only had a moderate association to requirement of ICU interventions. Neither transferring patients to a CSC nor the number of standard IV-tPA contraindications increased ICU interventions. CONCLUSIONS: Liberalized IV-tPA administration did not increase ICU interventions. Nearly all patients that required ICU interventions declared this need in triage, prior to ICU admission. This timing of ICU intervention use during triage is highly sensitive for whether a patient will require ongoing ICU-level care during hospital admission. Identifying ICU intervention use in triage may allow for more effective placement of post-IV-tPA patients in the appropriate inpatient care setting, leading to better utilization of scarce ICU resources.

Myeloid Notch1 deficiency activates the RhoA/ROCK pathway and aggravates hepatocellular damage in mouse ischemic livers.

Notch signaling plays an emerging role in the regulation of immune cell development and function during inflammatory response. Activation of the ras homolog gene family member A/Rho-associated protein kinase (ROCK) pathway promotes leukocyte accumulation in tissue injury. However, it remains unknown whether Notch signaling regulates ras homolog gene family member A/ROCK-mediated immune responses in liver ischemia and reperfusion (IR) injury. This study investigated intracellular signaling pathways regulated by Notch receptors in the IR-stressed liver and in vitro. In a mouse model of IR-induced liver inflammatory injury, we found that mice with myeloid-specific Notch1 knockout showed aggravated hepatocellular damage, with increased serum alanine aminotransferase levels, hepatocellular apoptosis, macrophage/neutrophil trafficking, and proinflammatory mediators compared to Notch1-proficient controls. Unlike in the controls, myeloid Notch1 ablation diminished hairy and enhancer of split-1 (Hes1) and augmented c-Jun N-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1), JNK, ROCK1, and phosphatase and tensin homolog (PTEN) activation in ischemic livers. Disruption of JSAP1 in myeloid-specific Notch1 knockout livers improved hepatocellular function and reduced JNK, ROCK1, PTEN, and toll-like receptor 4 activation. Moreover, ROCK1 knockdown inhibited PTEN and promoted Akt, leading to depressed toll-like receptor 4. In parallel in vitro studies, transfection of lentivirus-expressing Notch1 intracellular domain promoted Hes1 and inhibited JSAP1 in lipopolysaccharide-stimulated bone marrow-derived macrophages. Hes1 deletion enhanced JSAP1/JNK activation, whereas clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9-mediated JSAP1 knockout diminished ROCK1/PTEN and toll-like receptor 4 signaling. CONCLUSION: Myeloid Notch1 deficiency activates the ras homolog gene family member A/ROCK pathway and exacerbates hepatocellular injury by inhibiting transcriptional repressor Hes1 and inducing scaffold protein JSAP1 in IR-triggered liver inflammation; our findings underscore the crucial role of the Notch-Hes1 axis as a novel regulator of innate immunity-mediated inflammation and imply the therapeutic potential for the management of organ IR injury in transplant recipients. (Hepatology 2018;67:1041-1055).

MR perfusion lesions after TIA or minor stroke are associated with new infarction at 7 days.

OBJECTIVE: To investigate the relationship between acute perfusion-weighted imaging (PWI) lesions occurring within the first hours after a TIA or a minor brain infarction (BI) and the incidence of new BI detected on a systematic MRI at 1 week. METHODS: Consecutive patients who experienced a TIA or BI with a neurologic deficit that lasted <24 hours, did not receive any revascularization therapy (thrombolysis/thrombectomy), and underwent DWI/PWI at baseline and fluid-attenuated inversion recovery (FLAIR)/DWI 1 week after symptom onset were enrolled. Investigators blinded to clinical information independently assessed the presence of acute ischemic lesions on baseline DWI/PWI and follow-up DWI and FLAIR. Baseline and follow-up MRIs were then compared to determine the occurrence and location of new infarctions. RESULTS: Sixty-four patients met the inclusion criteria. Median (IQR) ABCD2 score was 4 (3-5). Median delay from onset to baseline and follow-up MRI was 5 (2-10) hours and 6 (5-7) days, respectively. MRI revealed an acute ischemic lesion on DWI and/or PWI in 38 patients. Nine patients (14%) had a new infarction on follow-up MRI. Each had a PWI and 4 had a DWI lesion on baseline MRI. All new BIs except one were asymptomatic and in the same location as the acute PWI lesion. CONCLUSIONS: Our results showed that 30% of the acute focal PWI lesions detected after a TIA are associated with a new BI at 1 week. Those new BIs may result from the progression of the initial ischemic injury.

Blockade of Notch signaling promotes acetaminophen-induced liver injury.

Liver injury after experimental acetaminophen treatment is mediated both by direct hepatocyte injury through a P450-generated toxic metabolite and indirectly by activated liver Kupffer cells and neutrophils. This study was designed to investigate the role of Notch signaling in the regulation of innate immune responses in acetaminophen (APAP)-induced liver injury. Using a mouse model of APAP-induced liver injury, wild-type (WT) and toll-like receptor 4 knockout (TLR4 KO) mice were injected intraperitoneally with APAP or PBS. Some animals were injected with γ-secretase inhibitor DAPT or DMSO vehicle. For the in vitro study, bone marrow-derived macrophages (BMMs) were transfected with Notch1 siRNA, TLR4 siRNA, and non-specific (NS) siRNA and stimulated with LPS. Indeed, paracetamol/acetaminophen-induced liver damage was worse after Notch blockade with DAPT in wild-type mice, which was accompanied by significantly increased ALT levels, diminished hairy and enhancer of split-1 (Hes1), and phosphorylated Stat3 and Akt but enhanced high mobility group box 1 (HMGB1), TLR4, NF-κB, and NLRP3 activation after APAP challenge. Mice receiving DAPT increased macrophage and neutrophil accumulation and hepatocellular apoptosis. However, TLR4 KO mice that received DAPT reduced APAP-induced liver damage and NF-κB, NLRP3, and cleaved caspase-1 activation. BMMs transfected with Notch1 siRNA reduced Hes1 and phosphorylated Stat3 and Akt but augmented HMGB1, TLR4, NF-κB, and NLRP3. Furthermore, TLR4 siRNA knockdown resulted in decreased NF-κB and NLRP3 and cleaved caspase-1 and IL-1ß levels following LPS stimulation. These results demonstrate that Notch signaling regulates innate NLRP3 inflammasome activation through regulation of HMGB1/TLR4/NF-κB activation in APAP-induced liver injury. Our novel findings underscore the critical role of the Notch1-Hes1 signaling cascade in the regulation of innate immunity in APAP-triggered liver inflammation. This might imply a novel therapeutic potential for the drug-induced damage-associated lethal hepatitis.

Phosphatase and tensin homolog-ß-catenin signaling modulates regulatory T cells and inflammatory responses in mouse liver ischemia/reperfusion injury.

The phosphatase and tensin homolog (PTEN) deleted on chromosome 10 plays an important role in regulating T cell activation during inflammatory response. Activation of ß-catenin is crucial for maintaining immune homeostasis. This study investigates the functional roles and molecular mechanisms by which PTEN-ß-catenin signaling promotes regulatory T cell (Treg) induction in a mouse model of liver ischemia/reperfusion injury (IRI). We found that mice with myeloid-specific phosphatase and tensin homolog knockout (PTENM-KO ) exhibited reduced liver damage as evidenced by decreased levels of serum alanine aminotransferase, intrahepatic macrophage trafficking, and proinflammatory mediators compared with the PTEN-proficient (floxed phosphatase and tensin homolog [PTENFL/FL ]) controls. Disruption of myeloid PTEN-activated b-catenin promoted peroxisome proliferator-activated receptor gamma (PPARγ)-mediated Jagged-1/Notch signaling and induced forkhead box P3 (FOXP3)1 Tregs while inhibiting T helper 17 cells. However, blocking of Notch signaling by inhibiting γ-secretase reversed myeloid PTEN deficiency-mediated protection in ischemia/reperfusion-triggered liver inflammation with reduced FOXP3+ and increased retinoid A receptor-related orphan receptor gamma t-mediated interleukin 17A expression in ischemic livers. Moreover, knockdown of ß-catenin or PPARγ in PTEN-deficient macrophages inhibited Jagged-1/Notch activation and reduced FOXP3+ Treg induction, leading to increased proinflammatory mediators in macrophage/T cell cocultures. In conclusion, our findings demonstrate that PTEN-ß-catenin signaling is a novel regulator involved in modulating Treg development and provides a potential therapeutic target in liver IRI. Liver Transplantation 23 813-825 2017 AASLD.

The myeloid heat shock transcription factor 1/ß-catenin axis regulates NLR family, pyrin domain-containing 3 inflammasome activation in mouse liver ischemia/reperfusion injury.

Heat shock transcription factor 1 (HSF1) has been implicated in the differential regulation of cell stress and disease states. ß-catenin activation is essential for immune homeostasis. However, little is known about the role of macrophage HSF1-ß-catenin signaling in the regulation of NLRP3 inflammasome activation during ischemia/reperfusion (I/R) injury (IRI) in the liver. This study investigated the functions and molecular mechanisms by which HSF1-ß-catenin signaling influenced NLRP3-mediated innate immune response in vivo and in vitro. Using a mouse model of IR-induced liver inflammatory injury, we found that mice with a myeloid-specific HSF1 knockout (HSF1M-KO ) displayed exacerbated liver damage based on their increased serum alanine aminotransferase levels, intrahepatic macrophage/neutrophil trafficking, and proinflammatory interleukin (IL)-1ß levels compared to the HSF1-proficient (HSF1FL/FL ) controls. Disruption of myeloid HSF1 markedly increased transcription factor X-box-binding protein (XBP1), NLR family, pyrin domain-containing 3 (NLRP3), and cleaved caspase-1 expression, which was accompanied by reduced ß-catenin activity. Knockdown of XBP1 in HSF1-deficient livers using a XBP1 small interfering RNA ameliorated hepatocellular functions and reduced NLRP3/cleaved caspase-1 and IL-1ß protein levels. In parallel in vitro studies, HSF1 overexpression increased ß-catenin (Ser552) phosphorylation and decreased reactive oxygen species (ROS) production in bone-marrow-derived macrophages. However, myeloid HSF1 ablation inhibited ß-catenin, but promoted XBP1. Furthermore, myeloid ß-catenin deletion increased XBP1 messenger RNA splicing, whereas a CRISPR/CRISPR-associated protein 9-mediated XBP1 knockout diminished NLRP3/caspase-1. CONCLUSION: The myeloid HSF1-ß-catenin axis controlled NLRP3 activation by modulating the XBP1 signaling pathway. HSF1 activation promoted ß-catenin, which, in turn, inhibited XBP1, leading to NLRP3 inactivation and reduced I/R-induced liver injury. These findings demonstrated that HSF1/ß-catenin signaling is a novel regulator of innate immunity in liver inflammatory injury and implied the therapeutic potential for management of sterile liver inflammation in transplant recipients. (Hepatology 2016;64:1683-1698).

Examining the effects of turnover intentions on organizational citizenship behaviors and deviance behaviors: A psychological contract approach.

Although turnover intentions are considered the most proximal antecedent of organizational exit, there is often temporal separation between thinking about leaving and actual exit. Using field data from 2 diverse samples of working adults, we explore a causal model of the effects of turnover intentions on employee behavior while they remain with the organization, focusing specifically on organizational citizenship behaviors (OCBs) and deviance behaviors (DBs). Utilizing expectancy theory as an explanatory framework, we argue that turnover intentions result in high levels of transactional contract orientation and low levels of relational contract orientation, which in turn lead to a decrease in the incidence of OCBs and an increase in the incidence of DBs. We first used a pilot study to investigate the direction of causality between turnover intentions and psychological contract orientations. Then, in Study 1, we tested our mediated model using a sample of employees from a large drug retailing chain. In Study 2, we expanded our model by arguing that the mediated effects are much stronger when the organization is deemed responsible for potential exit. We then tested our full model using a sample of employees from a large state-owned telecommunications corporation in China. Across both studies, results were generally consistent and supportive of our hypotheses. We discuss the implications of our findings for future theory, research, and practice regarding the management of both the turnover process and discretionary behaviors at work. (PsycINFO Database Record

Cerebellar encoding of multiple candidate error cues in the service of motor learning.

For learning to occur through trial and error, the nervous system must effectively detect and encode performance errors. To examine this process, we designed a set of oculomotor learning tasks with more than one visual object providing potential error cues, as would occur in a natural visual scene. A task-relevant visual target and a task-irrelevant visual background both influenced vestibulo-ocular reflex learning in rhesus monkeys. Thus, motor learning does not identify a single error cue based on behavioral relevance, but can be simultaneously influenced by more than one cue. Moreover, the relative weighting of the different cues could vary. If the speed of the visual target's motion on the retina was low (≪1°/s), background motion dominated learning, but if target speed was high, the effects of the background were suppressed. The target and background motion had similar, nonlinear effects on the putative neural instructive signals carried by cerebellar climbing fibers, but with a stronger influence of the background on the climbing fibers than on learning. In contrast, putative neural instructive signals carried by the simple spikes of Purkinje cells were influenced solely by the motion of the visual target. Because they are influenced by different cues during training, joint control of learning by the climbing fibers and Purkinje cells may expand the learning capacity of the cerebellar circuit.

Building a self-regulatory model of sleep deprivation and deception: the role of caffeine and social influence.

Employees are getting less sleep, which has been shown to deplete self-regulatory resources and increase unethical behavior (Barnes, Schaubroeck, Huth, & Ghumman, 2011; Christian & Ellis, 2011). In this study, we extend the original mediated model by examining the role of 2 moderators in the relationship between sleep deprivation, depletion, and deceptive behavior. First, we derive psychological arguments from the psychopharmacology literature to hypothesize that caffeine moderates the relationship between sleep deprivation and depletion by replenishing self-regulatory resources. Second, we draw from recent research in social psychology to hypothesize that social influence moderates the relationship between depletion and deceptive behavior, such that depleted individuals are less able to resist the negative influence of others. Results of a laboratory study provide support for our expanded model combining mediation and moderation, adding to our understanding of the role of sleep deprivation in the incidence of workplace deception. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Herpes simplex virus encephalitis is a trigger of brain autoimmunity.

In 5 prospectively diagnosed patients with relapsing post-herpes simplex encephalitis (HSE), N-methyl-D-aspartate receptor (NMDAR) antibodies were identified. Antibody synthesis started 1 to 4 weeks after HSE, preceding the neurological relapse. Three of 5 patients improved postimmunotherapy, 1 spontaneously, and 1 has started to improve. Two additional patients with NMDAR antibodies, 9 with unknown neuronal surface antibodies, and 1 with NMDAR and unknown antibodies, were identified during retrospective assessment of 34 HSE patients; the frequency of autoantibodies increased over time (serum, p=0.004; cerebrospinal fluid, p=0.04). The 3 retrospectively identified NMDAR antibody-positive patients also had evidence of relapsing post-HSE. Overall, these findings indicate that HSE triggers NMDAR antibodies and potentially other brain autoimmunity.

Examining the asymmetrical effects of goal faultlines in groups: a categorization-elaboration approach.

The purpose of this study was to use the categorization-elaboration model (CEM) to examine the asymmetrical effects of goal faultlines in groups, which are present when hypothetical dividing lines are created on the basis of different performance goals, splitting the group into subgroups. On the basis of the CEM, we expected groups with goal faultlines to exhibit higher levels of creative task performance than (a) groups with specific, difficult goals and (b) groups with do-your-best goals. We expected the benefits of goal faultlines to be due to increases in reflective reframing, which occurs when group members build on each other's ideas by shifting to alternate frames. However, we expected groups with goal faultlines to exhibit lower levels of routine task performance than (a) groups with do-your-best goals and (b) groups with specific, difficult goals, due to increased perceptions of loafing. Results from 87 groups generally supported our hypothesized model. Implications are discussed as well as possible limitations and directions for future research.

Surveying for "artifacts": the susceptibility of the OCB-performance evaluation relationship to common rater, item, and measurement context effects.

Despite the increased attention paid to biases attributable to common method variance (CMV) over the past 50 years, researchers have only recently begun to systematically examine the effect of specific sources of CMV in previously published empirical studies. Our study contributes to this research by examining the extent to which common rater, item, and measurement context characteristics bias the relationships between organizational citizenship behaviors and performance evaluations using a mixed-effects analytic technique. Results from 173 correlations reported in 81 empirical studies (N = 31,146) indicate that even after controlling for study-level factors, common rater and anchor point number similarity substantially biased the focal correlations. Indeed, these sources of CMV (a) led to estimates that were between 60% and 96% larger when comparing measures obtained from a common rater, versus different raters; (b) led to 39% larger estimates when a common source rated the scales using the same number, versus a different number, of anchor points; and (c) when taken together with other study-level predictors, accounted for over half of the between-study variance in the focal correlations. We discuss the implications for researchers and practitioners and provide recommendations for future research.

Elimination of climbing fiber instructive signals during motor learning.

The climbing fiber input to the cerebellum from the inferior olive is thought to act as a teacher whose activity controls the induction of motor learning. We designed training conditions that did not elicit instructive signals in the climbing fibers, but nevertheless induced robust and consistent motor learning in the vestibulo-ocular reflex of rhesus monkeys. Our results indicate that instructive signals in the climbing fibers are not necessary for cerebellum-dependent learning. Instead, instructive signals carried by either the climbing fibers or Purkinje cell simple spikes may be sufficient to induce motor learning, with additive effects occurring when both instructive signals are present during training.

Distinct patterns of stimulus generalization of increases and decreases in VOR gain.

Motor learning must be capable of increasing or decreasing the amplitude of movements to meet the demands of the environment. One way to implement such opposite learned changes would be to store them with bidirectional plasticity mechanisms (i.e., long-term potentiation and depression at the same synapses). At the behavioral level, this scheme should result in similar patterns of stimulus generalization of increases and decreases in movement amplitude because the same synapses would be modified but in opposite directions. To test this idea, we quantitatively compared the stimulus generalization of learned increases and decreases in the gain (amplitude) of the vestibuloocular reflex (VOR) in mice and in monkeys. When examined across different sinusoidal frequencies of head rotation, decreases in VOR gain generalized more than increases in gain. This difference was apparent not only in the gain, but also the phase (timing) of the VOR. Furthermore, this difference held when animals were trained with high-frequency rotational stimuli, a manipulation that enhances frequency generalization. Our results suggest that increases and decreases in VOR gain are not exact inverses at the circuit level. At one or more sites, the plasticity mechanisms supporting decreases in VOR gain must be less synapse-specific, or affect neurons more broadly tuned for head rotation frequency, than the mechanisms supporting increases in gain.