2,744 research outputs found

    Whatever It Takes: How and When Supervisor Bottom-Line Mentality Motivates Employee Contributions in the Workplace

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    Given that many organizations are competitive and finance centered, organizational leaders may lead with a primary focus on bottom-line attainment, such that they are perceived by their subordinates as having a bottom-line mentality (BLM) that entails pursuing bottom-line outcomes above all else. Yet, the field is limited in understanding why such a leadership approach affects employees’ positive and negative contributions in the workplace. Drawing on social exchange theory, we theorize that supervisors high in BLM can influence employees’ felt obligation toward the bottom line, which in turn can influence employees’ task performance and unethical pro-organizational behavior (UPB). We also examine employee ambition as a moderator of this process. Using three-wave, multisource data collected from the financial services industry, our results revealed that high-BLM supervisors elevate employee task performance as well as UPB by motivating employees’ felt obligation toward the bottom line. Furthermore, we found that employee ambition served as a first-stage moderator, such that the mediated relationships were stronger when employee ambition was high as opposed to low. Our findings break away from the dominant dysfunctional view of BLM and provide a more balanced view of this mentality

    Urinary excretion of RAS, BMP, and WNT pathway components in diabetic kidney disease.

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    Abstract The renin-angiotensin system (RAS), bone morphogenetic protein (BMP), and WNT pathways are involved in pathogenesis of diabetic kidney disease (DKD). This study characterized assays for urinary angiotensinogen (AGT), gremlin-1, and matrix metalloproteinase 7 (MMP-7), components of the RAS, BMP, and WNT pathways and examined their excretion in DKD. We measured urine AGT, gremlin-1, and MMP-7 in individuals with type 1 diabetes and prevalent DKD (n = 20) or longstanding (n = 61) or new-onset (n = 10) type 1 diabetes without DKD. These urine proteins were also quantified in type 2 DKD (n = 11) before and after treatment with candesartan. The utilized immunoassays had comparable inter- and intra-assay and intraindividual variation to assays used for urine albumin. Median (IQR) urine AGT concentrations were 226.0 (82.1, 550.3) and 13.0 (7.8, 20.0) μg/g creatinine in type 1 diabetes with and without DKD, respectively (P < 0.001). Median (IQR) urine gremlin-1 concentrations were 48.6 (14.2, 254.1) and 3.6 (1.7, 5.5) μg/g, respectively (P < 0.001). Median (IQR) urine MMP-7 concentrations were 6.0 (3.8, 10.5) and 1.0 (0.4, 2.9) μg/g creatinine, respectively (P < 0.001). Treatment with candesartan was associated with a reduction in median (IQR) urine AGT/creatinine from 23.5 (1.6, 105.1) to 2.0 (1.4, 13.7) μg/g, which did not reach statistical significance. Urine gremlin-1 and MMP-7 excretion did not decrease with candesartan. In conclusion, DKD is characterized by markedly elevated urine AGT, MMP-7, and gremlin-1. AGT decreased in response to RAS inhibition, suggesting that this marker reflects therapeutic response. Urinary components of the RAS, BMP, and WNT pathways may identify risk of DKD and aid development of novel therapeutics

    Dorsal Raphe Dopamine Neurons Modulate Arousal and Promote Wakefulness by Salient Stimuli

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    Ventral midbrain dopamine (DA) is unambiguously involved in motivation and behavioral arousal, yet the contributions of other DA populations to these processes are poorly understood. Here, we demonstrate that the dorsal raphe nucleus DA neurons are critical modulators of behavioral arousal and sleep-wake patterning. Using simultaneous fiber photometry and polysomnography, we observed time-delineated dorsal raphe nucleus dopaminergic (DRNDA) activity upon exposure to arousal-evoking salient cues, irrespective of their hedonic valence. We also observed broader fluctuations of DRNDA activity across sleep-wake cycles with highest activity during wakefulness. Both endogenous DRNDA activity and optogenetically driven DRNDA activity were associated with waking from sleep, with DA signal strength predictive of wake duration. Conversely, chemogenetic inhibition opposed wakefulness and promoted NREM sleep, even in the face of salient stimuli. Therefore, the DRNDA population is a critical contributor to wake-promoting pathways and is capable of modulating sleep-wake states according to the outside environment, wherein the perception of salient stimuli prompts vigilance and arousal

    The Immune Epitope Database 2.0

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    T-cell recognition is shaped by epitope sequence conservation in the host proteome and microbiome

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    Several mechanisms exist to avoid or suppress inflammatory T-cell immune responses that could prove harmful to the host due to targeting self-antigens or commensal microbes. We hypothesized that these mechanisms could become evident when comparing the immunogenicity of a peptide from a pathogen or allergen with the conservation of its sequence in the human proteome or the healthy human microbiome. Indeed, performing such comparisons on large sets of validated T-cell epitopes, we found that epitopes that are similar with self-antigens above a certain threshold showed lower immunogenicity, presumably as a result of negative selection of T cells capable of recognizing such peptides. Moreover, we also found a reduced level of immune recognition for epitopes conserved in the commensal microbiome, presumably as a result of peripheral tolerance. These findings indicate that the existence (and potentially the polarization) of T-cell responses to a given epitope is influenced and to some extent predictable based on its similarity to self-antigens and commensal antigens.Fil: Bresciani, Anne Gøther. Technical University of Denmark; Dinamarca. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Paul, Sinu. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Schommer, Nina. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Dillon, Myles B.. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Bancroft, Tara. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Greenbaum, Jason. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Sette, Alessandro. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina. Technical University of Denmark; DinamarcaFil: Peters, Bjoern. La Jolla Institute for Allergy and Immunology; Estados Unido

    Compensation for victims of sexual violence in South Africa : a human rights approach to remedial criminal compensation provisions

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    Includes abstract.Includes bibliographical references.The author questioned why state attorneys, prosecutors and magistrates/judges in South Africa rarely review the compensation concerns of sexual violence complainants and witnesses in criminal sentencing matters, and in quasi-criminal civil forfeiture proceedings, as is frequently done for other classes of complainants (namely, commercial crime complainants and victims of violent crime in general). A conclusion was reached, after conducting extensive research for this thesis, that offender and state compensation processes were sparingly utilized in cases of sexual violence, in part, due to institutional biases that resulted in discrimination. The above finding was substantiated by way of twenty-seven (27) interviews with criminal justice role-players, eight (8) court file case studies and forty-seven (47) victim surveys. The above subject matter is important because failures by criminal justice state role-players to review the compensation concerns of sexual violence victims, on account of biases, causes real harm to these vulnerable complainants. For example, research in this thesis confirmed that state and offender compensation can assist sexual violence complainants with their cultural obligations, court appearances and post-assault health expenses and to pre-empt compensation reviews on account of biases disrupts victims' post assault recoveries. Further, compensation can assist sexual violence complainants with security related expenses, including relocation costs, so as to avoid repeated victimization

    Xenopus fraseri: Mr. Fraser, where did your frog come from?

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    A comprehensive, accurate, and revisable alpha taxonomy is crucial for biodiversity studies, but is challenging when data from reference specimens are difficult to collect or observe. However, recent technological advances can overcome some of these challenges. To illustrate this, we used modern approaches to tackle a centuries-old taxonomic enigma presented by Fraser’s Clawed Frog, Xenopus fraseri, including whether X. fraseri is different from other species, and if so, where it is situated geographically and phylogenetically. To facilitate these inferences, we used high-resolution techniques to examine morphological variation, and we generated and analyzed complete mitochondrial genome sequences from all Xenopus species, including >150-year-old type specimens. Our results demonstrate that X. fraseri is indeed distinct from other species, firmly place this species within a phylogenetic context, and identify its minimal geographic distribution in northern Ghana and northern Cameroon. These data also permit novel phylogenetic resolution into this intensively studied and biomedically important group. Xenopus fraseri was formerly thought to be a rainforest endemic placed alongside species in the amieti species group; in fact this species occurs in arid habitat on the borderlands of the Sahel, and is the smallest member of the muelleri species group. This study illustrates that the taxonomic enigma of Fraser’s frog was a combined consequence of sparse collection records, interspecies conservation and intraspecific polymorphism in external anatomy, and type specimens with unusual morphology

    The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor

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    Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Pharmacologically enforced egress of hematopoietic stem cells from BM, or mobilization, has been achieved by directly or indirectly targeting the CXCL12/CXCR4 axis. Shortcomings of the standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone or in combination with the only approved CXCR4 antagonist, Plerixafor, continue to fuel the quest for new mobilizing agents. Using Protein Epitope Mimetics technology, a novel peptidic CXCR4 antagonist, POL5551, was developed. In vitro data presented herein indicate high affinity to and specificity for CXCR4. POL5551 exhibited rapid mobilization kinetics and unprecedented efficiency in C57BL/6 mice, exceeding that of Plerixafor and at higher doses also of G-CSF. POL5551-mobilized stem cells demonstrated adequate transplantation properties. In contrast to G-CSF, POL5551 did not induce major morphological changes in the BM of mice. Moreover, we provide evidence of direct POL5551 binding to hematopoietic stem and progenitor cells (HSPCs) in vivo, strengthening the hypothesis that CXCR4 antagonists mediate mobilization by direct targeting of HSPCs. In summary, POL5551 is a potent mobilizing agent for HSPCs in mice with promising therapeutic potential if these data can be orroborated in humans
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