CD40-Mediated Activation of the NF-κB2 Pathway

CD40 is a critical stimulatory receptor on antigen-presenting cells of the immune system. CD40-mediated activation of B cells is particularly important for normal humoral immune function. Engagement of CD40 by its ligand, CD154, on the surface of activated T cells initiates a variety of signals in B cells including the activation of MAP kinases and NF-κB. The transcriptional regulator NF-κB is in reality a family of factors that can promote B cell activation, differentiation, and proliferation. Complex – and only partially understood – biochemical mechanisms allow CD40 to trigger two distinct NF-κB activation pathways resulting in the activation of canonical (NF-κB1) and non-canonical (NF-κB2) NF-κB. This brief review provides a summary of mechanisms responsible for activation of the latter, which appears to be particularly important for enhancing the viability of B cells at various stages in their life cycle and may also contribute to the development of B cell malignancies. CD40 is also expressed by various cell types in addition to B cells, including T cells, macrophages, dendritic cells, as well as certain non-hematopoietic cells. Here too, while perhaps less extensively studied than in B cells, the CD40-mediated activation of NF-κB2 also appears to have important roles in cellular physiology

Revenge of the nerds revisited: Do accounting and finance majors differ from other business majors in their learning styles, and do they earn higher grades in a general business course?

Decades of research spanning a range of educational domains have confirmed that students differ in their learning styles and that student performance is impacted by the degree of fit between these styles and the teaching and assessment methods deployed in courses (Allinson & Hayes, 1988; Cegielski, Hazen & Rainer, 2011; Drissi & Amirat, 2017; Honn & Ugrin, 2012; Visser, McChlery & Vreken, 2006.) In this study, the researchers investigate whether a capstone business course— designed to accommodate a diverse range of learning styles— can succeed in leveling the playing field, yielding results showing no significant differences in course grades as a function of students’ learning styles. The second focus is examining the myth of bookish, nerdy accountants (Brighenti, 2010; Tuttle, 2016). The findings ‘bust’ the myth that more ‘bookish’ accounting and finance majors will earn higher course grades in a general business course. The paper concludes by noting some important implications of our study for future research and practice

Requirement for TRAF3 in Signaling by LMP1 But Not CD40 in B Lymphocytes

CD40, a member of the tumor necrosis factor receptor family, and the Epstein-Barr virus–encoded oncoprotein latent membrane protein 1 (LMP1) share several tumor necrosis factor receptor–associated factor (TRAF) adaptor proteins for signaling. Among these, TRAF3 was the first identified to directly bind both receptors, yet its role remains a mystery. To address this, we generated B cell lines deficient in TRAF3 by homologous recombination. We found that CD40 signals were normal in the absence of TRAF3, with the exception of moderately enhanced c-Jun NH2-terminal kinase (JNK) activation and antibody secretion. In sharp contrast, LMP1 signaling was markedly defective in TRAF3−/− B cells. LMP1-induced activation of JNK and nuclear factor κB, up-regulation of CD23 and CD80, and antibody secretion were substantially affected by TRAF3 deficiency. Reconstitution of TRAF3 expression decreased CD40-induced JNK activation and antibody secretion, and fully restored LMP1 signaling. Although TRAF2 is widely believed to be important for LMP1 function, LMP1 signaling was intact in TRAF2−/− B cells. Our data reveal that CD40 and LMP1 unexpectedly use TRAF3 in different ways, and that TRAF3 is required for LMP1-mediated activation of B cells

Measuring the Effectiveness of a Workplace Diversity Training Program: A Field Study

Although workplace diversity training has been a common practice in American companies for the past 15 years, little systematic assessment has been conducted. It appears that many organizational leaders and human resource professionals simply assume that the training activities had a positive effect. In the current study, a large manufacturing organization was interested in implementing a diversity program company-wide. However, before doing so, a pilot study was conducted with a critical layer of senior management to determine whether the training would be effective. The Workplace Diversity Survey was administered: (a) one week prior to the training, (b) the week immediately after the training was completed, and (c) three months later. The instrument measured the overall efficacy of the diversity training as well as five specific dimensions of participant perceptions. The results demonstrated that the program participants significantly increased both their overall and dimensional scores. This improvement was maintained throughout the period of study. Implications for the evaluation of diversity training and the use of executive management as a pilot group were discussed

HOIL-1L Interacting Protein (HOIP) as an NF-κB Regulating Component of the CD40 Signaling Complex

The tumor necrosis factor receptor (TNFR) superfamily mediates signals critical for regulation of the immune system. One family member, CD40, is important for the efficient activation of antibody-producing B cells and other antigen-presenting cells. The molecules and mechanisms that mediate CD40 signaling are only partially characterized. Proteins known to interact with the cytoplasmic domain of CD40 include members of the TNF receptor-associated factor (TRAF) family, which regulate signaling and serve as links to other signaling molecules. To identify additional proteins important for CD40 signaling, we used a combined stimulation/immunoprecipitation procedure to isolate CD40 signaling complexes from B cells and characterized the associated proteins by mass spectrometry. In addition to known CD40-interacting proteins, we detected SMAC/DIABLO, HTRA2/Omi, and HOIP/RNF31/PAUL/ZIBRA. We found that these previously unknown CD40-interacting partners were recruited in a TRAF2-dependent manner. HOIP is a ubiquitin ligase capable of mediating NF-κB activation through the ubiquitin-dependent activation of IKKγ. We found that a mutant HOIP molecule engineered to lack ubiquitin ligase activity inhibited the CD40-mediated activation of NF-κB. Together, our results demonstrate a powerful approach for the identification of signaling molecules associated with cell surface receptors and indicate an important role for the ubiquitin ligase activity of HOIP in proximal CD40 signaling

Tolerance of Novel Toxins through Generalized Mechanisms: Simulating Gradual Host Shifts of ButterfliesKristin

Organisms encounter a wide range of toxic compounds in their environments, from chemicals that serve anticonsumption or anticompetition functions to pollutants and pesticides. Although we understand many detoxification mechanisms that allow organisms to consume toxins typical of their diet, we know little about why organisms vary in their ability to tolerate entirely novel toxins. We tested whether variation in generalized stress responses, such as antioxidant pathways, may underlie variation in reactions to novel toxins and, if so, their associated costs. We used an artificial diet to present cabbage white butterfly caterpillars (Pieris rapae) with plant material containing toxins not experienced in their evolutionary history. Families that maintained high performance (e.g., high survival, fast development time, large body size) on diets containing one novel toxic plant also performed well when exposed to two other novel toxic plants, consistent with a generalized response. Variation in constitutive (but not induced) expression of genes involved in oxidative stress responses was positively related to performance on the novel diets. While we did not detect reproductive trade-offs of this generalized response, there was a tendency to have less melanin investment in the wings, consistent with the role of melanin in oxidative stress responses. Taken together, our results support the hypothesis that variation in generalized stress responses, such as genes involved in oxidative stress responses, may explain the variation in tolerance to entirely novel toxins and may facilitate colonization of novel hosts and environments

Analysis of Hepatitis B Virus Genotype D in Greenland Suggests the Presence of a Novel Quasi-Subgenotype

A disproportionate number of Greenland's Inuit population are chronically infected with Hepatitis B virus (HBV; 5-10%). HBV genotypes B and D are most prevalent in the circumpolar Arctic. Here, we report 39 novel HBV/D sequences from individuals residing in southwestern Greenland. We performed phylodynamic analyses with ancient HBV DNA calibrators to investigate the origin and relationship of these taxa to other HBV sequences. We inferred a substitution rate of 1.4 × 10-5 [95% HPD 8.8 × 10-6, 2.0 × 10-5] and a time to the most recent common ancestor of 629 CE [95% HPD 37-1138 CE]. The Greenland taxa form a sister clade to HBV/D2 sequences, specifically New Caledonian and Indigenous Taiwanese sequences. The Greenland sequences share amino acid signatures with subgenotypes D1 and D2 and ~97% sequence identity. Our results suggest the classification of these novel sequences does not fit within the current nomenclature. Thus, we propose these taxa be considered a novel quasi-subgenotype