Air Force Work Interest Navigator (AF-WIN) to improve person-job match: Development, validation, and initial implementation.

This article describes development and validation of a web-based vocational interest tool designed to help recruits and re-trainees identify enlisted career fields that match their preferences for work contexts, activities, and functional roles in support of the Air Force mission. The tool has recently been implemented for use by members considering re-training, and is undergoing pilot testing for potential use in the recruiting process. We first describe how the AF-WIN was developed, based on adaptation of the taxonomy from a Navy vocational interest tool (Navy's Job Opportunities in the Navy [JOIN]), followed by surveys of subject matter experts (SMEs) in 132 Air Force career fields on relevant job markers. We then describe a validation study in which job incumbents completed the AF-WIN and reported their level of job satisfaction within their current career field; results show that incumbents the AF-WIN algorithm identified as a good match for their career field reported substantially higher levels of job satisfaction than incumbents identified as a relatively poor match based on the tool. Finally, we provide results from initial beta-testing of the tool in a sample of recent enlisted trainees on perceived accuracy, utility, and functionality of the tool for use in the initial job assignment process.

Denial and Empathy: Partners in Employee Trust Repair?

Prior research on trust repair has focused primarily on investigating verbal responses to breaches of trust. Although consistently implicated in violations, the role of affect in the repair process has been mostly ignored. Using a scenario-based paradigm, we conducted an experimental study to examine the value of mistrusted party's empathy, specific responses to an integrity-based violation (apology vs. denial), and nature of consequences (personal vs. organizational), as well as their interactive effects, on trust repair. Consequently, we sought to merge work on verbal responses with affect. Major findings indicated that presence of mistrusted party's empathy functioned to repair trust better than its absence and, when coupled with a denial of culpability, produced markedly increased perceptions of violator's integrity. These findings contribute to our understanding of how leaders influence followers through affect, informing both emotion and trust theory.

A Comparison of the Effects of Ethics Training on International and US Students.

As scientific and engineering efforts become increasingly global in nature, the need to understand differences in perceptions of research ethics issues across countries and cultures is imperative. However, investigations into the connection between nationality and ethical decision-making in the sciences have largely generated mixed results. In Study 1 of this paper, a measure of biases and compensatory strategies that could influence ethical decisions was administered. Results from this study indicated that graduate students from the United States and international graduate students studying in the US are prone to different biases. Based on these findings, recommendations are made for developing ethics education interventions to target these decision-making biases. In Study 2, we employed an ethics training intervention based on ethical sensemaking and used a well-established measure of ethical decision-making that more fully captures the content of ethical judgment. Similar to Study 1, the results obtained in this study suggest differences do exist between graduate students from the US and international graduate students in ethical decision-making prior to taking the research ethics training. However, similar effects were observed for both groups following the completion of the ethics training intervention.

Improving ethical knowledge and sensemaking from cases through elaborative interrogation and outcome valence.

The case-based approach to learning is popular among many applied fields. However, results of case-based education vary widely on case content and case presentation. This study examined two aspects of case-based education-outcome valence and case elaboration methods-in a two-day case-based Responsible Conduct of Research (RCR) ethics education program. Results suggest that outcome information is an integral part of a quality case. Furthermore, valence consistent outcomes may have certain advantages over mixed valence outcome information. Finally, students enjoy and excel working with case material, and the use of elaborative interrogation techniques can significantly improve internally-focused ethical sensemaking strategies associated with personal biases, constraints, and emotions.

Case-based ethics instruction: the influence of contextual and individual factors in case content on ethical decision-making.

Cases have been employed across multiple disciplines, including ethics education, as effective pedagogical tools. However, the benefit of case-based learning in the ethics domain varies across cases, suggesting that not all cases are equal in terms of pedagogical value. Indeed, case content appears to influence the extent to which cases promote learning and transfer. Consistent with this argument, the current study explored the influences of contextual and personal factors embedded in case content on ethical decision-making. Cases were manipulated to include a clear description of the social context and the goals of the characters involved. Results indicated that social context, specifically the description of an autonomy-supportive environment, facilitated execution of sense making processes and resulted in greater decision ethicality. Implications for designing optimal cases and case-based training programs are discussed.

Effects of alternative outcome scenarios and structured outcome evaluation on case-based ethics instruction.

Case-based instruction has been regarded by many as a viable alternative to traditional lecture-based education and training. However, little is known about how case-based training techniques impact training effectiveness. This study examined the effects of two such techniques: (a) presentation of alternative outcome scenarios to a case, and (b) conducting a structured outcome evaluation. Consistent with the hypotheses, results indicate that presentation of alternative outcome scenarios reduced knowledge acquisition, reduced sensemaking and ethical decision-making strategy use, and reduced decision ethicality. Conducting a structured outcome evaluation had no impact on these outcomes. Results indicate that those who use case-based instruction should take care to use clear, less complex cases with only a singular outcome if they are seeking these types of outcomes.

Case-based knowledge and ethics education: improving learning and transfer through emotionally rich cases.

Case-based instruction is a stable feature of ethics education, however, little is known about the attributes of the cases that make them effective. Emotions are an inherent part of ethical decision-making and one source of information actively stored in case-based knowledge, making them an attribute of cases that likely facilitates case-based learning. Emotions also make cases more realistic, an essential component for effective case-based instruction. The purpose of this study was to investigate the influence of emotional case content, and complementary socio-relational case content, on case-based knowledge acquisition and transfer on future ethical decision-making tasks. Study findings suggest that emotional case content stimulates retention of cases and facilitates transfer of ethical decision-making principles demonstrated in cases.

An investigation of case-based instructional strategies on learning, retention, and ethical decision-making.

Case-based instruction has been successfully employed by educators across various fields; however, little is known about how individuals work with cases during the learning process. We examined two well-established instructional strategies: elaboration and self-development of narratives. Participants were randomly assigned to (1) elaborate on a given case, (2) develop their own case, (3) elaborate on a self-developed case, or (4) a control condition. Findings indicated that those who elaborated on a given case and the control group outperformed the other treatment groups in terms of case-based knowledge acquisition, execution of sensemaking processes, utilization of ethical decision-making (EDM) strategies, and performance on two EDM measures. Implications for use of instructional strategies in ethics training programs are discussed.

Case-based ethics education: the impact of cause complexity and outcome favorability on ethicality.

Case-based learning has been used across multiple disciplines, including ethics education, as an effective instructional tool. However, the value of case-based learning in ethics education has varied widely regarding case quality. Case content may significantly impact the ability of case-based ethics education to promote knowledge acquisition and knowledge transfer to future situations requiring ethical decision-making. This study examined two critical areas of ethical case content--causes and outcomes. Complexity of described causes and outcome favorability were manipulated in two ethical cases used during an ethics education course. Results suggest that including information in case studies reflecting clear, simple key causes and negative outcomes results in better ethical sensemaking and ethical decision-making. Implications regarding case content and case-based ethics education are explored.

Signaling and cytoskeletal requirements in erythroblast enucleation.

To understand the role of cytoskeleton and membrane signaling molecules in erythroblast enucleation, we developed a novel analysis protocol of multiparameter high-speed cell imaging in flow. This protocol enabled us to observe F-actin and phosphorylated myosin regulatory light chain (pMRLC) assembled into a contractile actomyosin ring (CAR) between nascent reticulocyte and nucleus, in a population of enucleating erythroblasts. CAR formation and subsequent enucleation were not affected in murine erythroblasts with genetic deletion of Rac1 and Rac2 GTPases because of compensation by Rac3. Pharmacologic inhibition or genetic deletion of all Rac GTPases altered the distribution of F-actin and pMRLC and inhibited enucleation. Erythroblasts treated with NSC23766, cytochalasin-D, colchicine, ML7, or filipin that inhibited Rac activity, actin or tubulin polymerization, MRLC phosphorylation, or lipid raft assembly, respectively, exhibited decreased enucleation efficiency, as quantified by flow cytometry. As assessed by high-speed flow-imaging analysis, colchicine inhibited erythroblast polarization, implicating microtubules during the preparatory stage of enucleation, whereas NSC23766 led to absence of lipid raft assembly in the reticulocyte-pyrenocyte border. In conclusion, enucleation is a multistep process that resembles cytokinesis, requiring establishment of cell polarity through microtubule function, followed by formation of a contractile actomyosin ring, and coalescence of lipid rafts between reticulocyte and pyrenocyte.

Gene targeting implicates Cdc42 GTPase in GPVI and non-GPVI mediated platelet filopodia formation, secretion and aggregation.

BACKGROUND: Cdc42 and Rac1, members of the Rho family of small GTPases, play critical roles in actin cytoskeleton regulation. We have shown previously that Rac1 is involved in regulation of platelet secretion and aggregation. However, the role of Cdc42 in platelet activation remains controversial. This study was undertaken to better understand the role of Cdc42 in platelet activation. METHODOLOGY/PRINCIPAL FINDINGS: We utilized the Mx-cre;Cdc42(lox/lox) inducible mice with transient Cdc42 deletion to investigate the involvement of Cdc42 in platelet function. The Cdc42-deficient mice exhibited a significantly reduced platelet count than the matching Cdc42(+/+) mice. Platelets isolated from Cdc42(-/-), as compared to Cdc42(+/+), mice exhibited (a) diminished phosphorylation of PAK1/2, an effector molecule of Cdc42, (b) inhibition of filopodia formation on immobilized CRP or fibrinogen, (c) inhibition of CRP- or thrombin-induced secretion of ATP and release of P-selectin, (d) inhibition of CRP, collagen or thrombin induced platelet aggregation, and (e) minimal phosphorylation of Akt upon stimulation with CRP or thrombin. The bleeding times were significantly prolonged in Cdc42(-/-) mice compared with Cdc42(+/+) mice. CONCLUSION/SIGNIFICANCE: Our data demonstrate that Cdc42 is required for platelet filopodia formation, secretion and aggregation and therefore plays a critical role in platelet mediated hemostasis and thrombosis.

R-Ras and Rac GTPase cross-talk regulates hematopoietic progenitor cell migration, homing, and mobilization.

Adult hematopoietic progenitor cells (HPCs) are maintained by highly coordinated signals in the bone marrow. The molecular mechanisms linking intracellular signaling network of HPCs with their microenvironment remain poorly defined. The Rho family GTPase Rac1/Rac2 has previously been implicated in cell functions involved in HPC maintenance, including adhesion, migration, homing, and mobilization. In the present studies we have identified R-Ras, a member of the Ras family, as a key signal mediator required for Rac1/Rac2 activation. We found that whereas Rac1 activity is up-regulated upon stem cell factor, integrin, or CXCL12 stimulation, R-Ras activity is inversely up-regulated. Expression of a constitutively active R-Ras mutant resulted in down-regulation of Rac1-activity whereas deletion of R-Ras led to an increase in Rac1/Rac2 activity and signaling. R-Ras(-/-) HPCs displayed a constitutively assembled cortical actin structure and showed increased directional migration. Rac1/Rac2 inhibition reversed the migration phenotype of R-Ras(-/-) HPCs, similar to that by expressing an R-Ras active mutant. Furthermore, R-Ras(-/-) mice showed enhanced responsiveness to G-CSF for HPC mobilization and exhibited decreased bone marrow homing. Transplantation experiments indicate that the R-Ras deficiency-induced HPC mobilization is a HPC intrinsic property. These results indicate that R-Ras is a critical regulator of Rac signaling required for HPC migration, homing, and mobilization.

Cdc42 regulates bone modeling and remodeling in mice by modulating RANKL/M-CSF signaling and osteoclast polarization.

The modeling and remodeling of bone requires activation and polarization of osteoclasts, achieved by reorganization of the cytoskeleton. Members of the Rho subfamily of small GTPases, including Cdc42, are known regulators of cytoskeletal components, but the role of these proteins in bone physiology and pathophysiology remains unclear. Here, we examined loss-of-function mice in which Cdc42 was selectively ablated in differentiated osteoclasts and gain-of-function animals wherein Cdc42Gap, a protein that inactivates the small GTPase, was deleted globally. Cdc42 loss-of-function mice were osteopetrotic and resistant to ovariectomy-induced bone loss, while gain-of-function animals were osteoporotic. Isolated Cdc42-deficient osteoclasts displayed suppressed bone resorption, while osteoclasts with increased Cdc42 activity had enhanced resorptive capacity. We further demonstrated that Cdc42 modulated M-CSF-stimulated cyclin D expression and phosphorylation of Rb and induced caspase 3 and Bim, thus contributing to osteoclast proliferation and apoptosis rates. Furthermore, Cdc42 was required for multiple M-CSF- and RANKL-induced osteoclastogenic signals including activation and expression of the differentiation factors MITF and NFATc1 and was a component of the Par3/Par6/atypical PKC polarization complex in osteoclasts. These data suggest that Cdc42 regulates osteoclast formation and function and may represent a promising therapeutic target for prevention of pathological bone loss.

Rac1 targeting suppresses p53 deficiency-mediated lymphomagenesis.

Mutation of the p53 tumor suppressor is associated with disease progression, therapeutic resistance, and poor prognosis in patients with lymphoid malignancies and can occur in approximately 50% of Burkitt lymphomas. Thus, new therapies are needed to specifically target p53-deficient lymphomas with increased efficacy. In the current study, the specific impact of inhibition of the small GTPase Rac1 on p53-deficient B- and T-lymphoma cells was investigated. p53 deficiency resulted in increased Rac1 activity in both B-cell and T-cell lines, and its suppression was able to abrogate p53 deficiency-mediated lymphoma cell proliferation. Further, Rac targeting resulted in increased apoptosis via a p53-independent mechanism. By probing multiple signaling axes and performing rescue studies, we show that the antiproliferative effect of Rac1 targeting in lymphoma cells may involve the PAK and Akt signaling pathway, but not the mitogen-activated protein (MAP) kinase pathway. The effects of inhibition of Rac1 were extended in vivo where Rac1 targeting was able to specifically impair p53-deficient lymphoma cell growth in mouse xenografts and postpone lymphomagenesis onset in murine transplantation models. Because the Rac1 signaling axis is a critical determinant of apoptosis and tumorigenesis, it may represent an important basis for therapy in the treatment of p53-deficient lymphomas.

Rac1 and Rac2 GTPases are necessary for early erythropoietic expansion in the bone marrow but not in the spleen.

BACKGROUND: The small Rho GTPases Rac1 and Rac2 have both overlapping and distinct roles in actin organization, cell survival, and proliferation in various hematopoietic cell lineages. The role of these Rac GTPases in erythropoiesis has not yet been fully elucidated. DESIGN AND METHODS: Cre-recombinase-induced deletion of Rac1 genomic sequence was accomplished on a Rac2-null genetic background, in mouse hematopoietic cells in vivo. The erythroid progenitors and precursors in the bone marrow and spleen of these genetically engineered animals were evaluated by colony assays and flow cytometry. Apoptosis and proliferation of the different stages of erythroid progenitors and precursors were evaluated by flow cytometry. RESULTS: Erythropoiesis in Rac1(-/-);Rac2(-/-) mice is characterized by abnormal burst-forming unit-erythroid colony morphology and decreased numbers of megakaryocyte-erythrocyte progenitors, erythroid colony-forming units, and erythroblasts in the bone marrow. In contrast, splenic erythropoiesis is increased. Combined Rac1 and Rac2 deficiency compromises proliferation of the megakaryocyte-erythrocyte progenitor population in the bone marrow, while it allows increased survival and proliferation of megakaryocyte-erythrocyte progenitors in the spleen. Conclusions These data suggest that Rac1 and Rac2 GTPases are essential for normal bone marrow erythropoiesis but that they are dispensable for erythropoiesis in the spleen, implying different signaling pathways for homeostatic and stress erythropoiesis.

Rac GTPases regulate the morphology and deformability of the erythrocyte cytoskeleton.

Actin oligomers are a significant structural component of the erythrocyte cytoskeleton. Rac1 and Rac2 GTPases regulate actin structures and have multiple overlapping as well as distinct roles in hematopoietic cells; therefore, we studied their role in red blood cells (RBCs). Conditional gene targeting with a loxP-flanked Rac1 gene allowed Crerecombinase-induced deletion of Rac1 on a Rac2 null genetic background. The Rac1(-/-);Rac2(-/-) mice developed microcytic anemia with a hemoglobin drop of about 20% and significant anisocytosis and poikilocytosis. Reticulocytes increased more than 2-fold. Rac1(-/-);Rac2(-/-) RBCs stained with rhodamine-phalloidin demonstrated F-actin meshwork gaps and aggregates under confocal microscopy. Transmission electron microscopy of the cytoskeleton demonstrated junctional aggregates and pronounced irregularity of the hexagonal spectrin scaffold. Ektacytometry confirmed that these cytoskeletal changes in Rac1(-/-);Rac2(-/-) erythrocytes were associated with significantly decreased cellular deformability. The composition of the cytoskeletal proteins was altered with an increased actin-to-spectrin ratio and increased phosphorylation (Ser724) of adducin, an F-actin capping protein. Actin and phosphorylated adducin of Rac1(-/-);Rac2(-/-) erythrocytes were more easily extractable by Triton X-100, indicating weaker association to the cytoskeleton. Thus, deficiency of Rac1 and Rac2 GTPases in mice alters actin assembly in RBCs and causes microcytic anemia with reticulocytosis, implicating Rac GTPases as dynamic regulators of the erythrocyte cytoskeleton organization.