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Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma (KS) and multiple types of B cell malignancies. Emerging evidence demonstrates that KSHV reprograms host-cell central carbon metabolic pathways, which contributes to viral persistence and tumorigenesis. However, the mechanisms underlying KSHV-mediated metabolic reprogramming remain poorly understood. Carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD) is a key enzyme of the de novo pyrimidine synthesis, and was recently identified to deamidate the NF-κB subunit RelA to promote aerobic glycolysis and cell proliferation. Here we report that KSHV infection exploits CAD for nucleotide synthesis and glycolysis. Mechanistically, KSHV vCyclin binds to and hijacks cyclin-dependent kinase CDK6 to phosphorylate Ser-1900 on CAD, thereby activating CAD-mediated pyrimidine synthesis and RelA-deamidation-mediated glycolytic reprogramming. Correspondingly, genetic depletion or pharmacological inhibition of CDK6 and CAD potently impeded KSHV lytic replication and thwarted tumorigenesis of primary effusion lymphoma (PEL) cells in vitro and in vivo. Altogether, our work defines a viral metabolic reprogramming mechanism underpinning KSHV oncogenesis, which may spur the development of new strategies to treat KSHV-associated malignancies and other diseases. The oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV) is known to reprogram cellular metabolism. Here, Wan et al show that viral Cyclin exploits host nucleotide synthesis and glycolysis to support KSHV pathogenesis.

This research examines how one's construal level of a crisis differs by crisis type, and how the interplay of crisis type (self-threatening vs. society-threatening) and apology appeal type (emotional vs. informational) impacts the effectiveness of apology messages in a corporate crisis context. Findings indicate that one's mental construal toward a crisis varies by crisis type, with a self-threatening crisis leading to a lower level of construal than a society-threatening one. Findings further suggest that in a society-threatening crisis condition, an informational apology was more effective than an emotional one. However, in a self-threatening crisis condition, there was no significant difference between two different message types. These findings offer valuable guidelines for developing effective crisis response strategy.

The major function of the lymphatic system is to drain interstitial fluid from tissue. Functional drainage causes increased fluid flow that triggers lymphatic expansion, which is conceptually similar to hypoxia-triggered angiogenesis. Here, we have identified a mechanotransduction pathway that translates laminar flow-induced shear stress to activation of lymphatic sprouting. While low-rate laminar flow commonly induces the classic shear stress responses in blood endothelial cells and lymphatic endothelial cells (LECs), only LECs display reduced Notch activity and increased sprouting capacity. In response to flow, the plasma membrane calcium channel ORAI1 mediates calcium influx in LECs and activates calmodulin to facilitate a physical interaction between Krüppel-like factor 2 (KLF2), the major regulator of shear responses, and PROX1, the master regulator of lymphatic development. The PROX1/KLF2 complex upregulates the expression of DTX1 and DTX3L. DTX1 and DTX3L, functioning as a heterodimeric Notch E3 ligase, concertedly downregulate NOTCH1 activity and enhance lymphatic sprouting. Notably, overexpression of the calcium reporter GCaMP3 unexpectedly inhibited lymphatic sprouting, presumably by disturbing calcium signaling. Endothelial-specific knockouts of Orai1 and Klf2 also markedly impaired lymphatic sprouting. Moreover, Dtx3l loss of function led to defective lymphatic sprouting, while Dtx3l gain of function rescued impaired sprouting in Orai1 KO embryos. Together, the data reveal a molecular mechanism underlying laminar flow-induced lymphatic sprouting.

Although group network characteristics significantly influence a group’s ability to exchange and absorb knowledge by listening to group members’ opinions, previous research on voice behavior has not yet fully addressed the social and relational factors in work groups that affect group-level voice. Specifically, in line with the “dark side of social capital” argument, this study examined the effects of group network density on group voice. In addition, drawing on the notion of status conflict, we further examined the moderating role of status conflict on the relationship between group network density and group voice. Using data from 55 work groups, we found an inverted U-shaped relationship between group network density and group voice. Moreover, we found that status conflict moderated the inverted-U effect of group density on group voice, such that when status conflict was high, (1) the overall level of group voice was reduced and (2) group voice decreased faster on the downward side of the inverted-U curve. Herein, we discuss the theoretical and practical implications of these results with relation to effective group management.

Schlemm's canal (SC) is a specialized vascular structure in the eye that functions to drain aqueous humor from the intraocular chamber into systemic circulation. Dysfunction of SC has been proposed to underlie increased aqueous humor outflow (AHO) resistance, which leads to elevated ocular pressure, a factor for glaucoma development in humans. Here, using lymphatic and blood vasculature reporter mice, we determined that SC, which originates from blood vessels during the postnatal period, acquires lymphatic identity through upregulation of prospero homeobox protein 1 (PROX1), the master regulator of lymphatic development. SC expressed lymphatic valve markers FOXC2 and integrin α9 and exhibited continuous vascular endothelial-cadherin (VE-cadherin) junctions and basement membrane, similar to collecting lymphatics. SC notably lacked luminal valves and expression of the lymphatic endothelial cell markers podoplanin and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1). Using an ocular puncture model, we determined that reduced AHO altered the fate of SC both during development and under pathologic conditions; however, alteration of VEGF-C/VEGFR3 signaling did not modulate SC integrity and identity. Intriguingly, PROX1 expression levels linearly correlated with SC functionality. For example, PROX1 expression was reduced or undetectable under pathogenic conditions and in deteriorated SCs. Collectively, our data indicate that PROX1 is an accurate and reliable biosensor of SC integrity and identity.

Do lymphatic vessels support cancer cells? Or are they vessels that help suppress cancer development? It is known that the lymphatic system is a vehicle for tumor metastasis and that the lymphangiogenic regulator VEGF-C supports the tumor. One such role of VEGF-C is the suppression of the immune response to cancer. The lymphatic system has also been correlated with an increase in interstitial fluid pressure of the tumor microenvironment. On the other hand, lymphatic vessels facilitate immune surveillance to mount an immune response against tumors with the support of VEGF-C. Furthermore, the activation of lymphatic fluid drainage may prove to filter and decrease tumor interstitial fluid pressure. In this review, we provide an overview of the dynamic between lymphatics, cancer, and tumor fluid pressure to suggest that lymphatic vessels may be used as an antitumor therapy due to their capabilities of immune surveillance and fluid pressure drainage. The application of this potential may help to prevent tumor proliferation or increase the efficacy of drugs that target cancer.

Drawing on the job demands–resources model, we suggest and test a motivational mechanism that underlies the relationship between leader boundary-spanning behavior and employee voice behavior. Based on the field survey data of 383 leader-employee pairs collected from various organizations in South Korea, the results of our mediation model showed that leader boundary-spanning behavior, as a potential job resource, enhances employee voice behavior by increasing employee self-efficacy. The results of our moderated mediation model also showed that the focal leader’s abusive supervision, as a potential job demand, could attenuate the beneficial effect of leader boundary-spanning behavior on employee voice behavior by diminishing employee self-efficacy. These findings highlight the importance of leader boundary-spanning behavior in enhancing employee voice behavior, the roles of employee self-efficacy as a key mediating mechanism, and the focal leader’s abusive supervision as a preventable boundary condition within these relationships. Theoretical and practical implications are discussed.

The purpose of this study is to explore the mechanisms by which leader humor affects followers’ change-oriented organizational citizenship behavior. Specifically, we examine the mediation effect of team commitment in the leader humor–change-oriented organizational citizenship behavior link and whether it varied by leader Machiavellianism. Using multi-sourced data from the four battalions of the Republic of Korean Army, our findings show that team commitment mediated the positive relationship between leaders’ affiliative humor and followers’ change-oriented organizational citizenship behavior. Furthermore, the mediated relationship was stronger when leader Machiavellianism was lower. On the other hand, we found no support for the negative relationship between leaders’ aggressive humor and followers’ change-oriented organizational citizenship behavior. Theoretical and practical implications are discussed.

The lymphatic system plays a key role in tissue fluid homeostasis, immune cell trafficking, and fat absorption. We previously reported a bacterial artificial chromosome (BAC)-based lymphatic reporter mouse, where EGFP is expressed under the regulation of the Prox1 promoter. This reporter line has been widely used to conveniently visualize lymphatic vessels and other Prox1-expressing tissues such as Schlemm’s canal. However, mice have a number of experimental limitations due to small body size. By comparison, laboratory rats are larger in size and more closely model the metabolic, physiological, and surgical aspects of humans. Here, we report development of a novel lymphatic reporter rat using the mouse Prox1-EGFP BAC. Despite the species mismatch, the mouse Prox1-EGFP BAC enabled a reliable expression of EGFP in Prox1-expressing cells of the transgenic rats and allowed a convenient visualization of all lymphatic vessels, including those in the central nervous system, and Schlemm’s canal. To demonstrate the utility of this new reporter rat, we studied the contractile properties and valvular functions of mesenteric lymphatics, developed a surgical model for vascularized lymph node transplantation, and confirmed Prox1 expression in venous valves. Together, Prox1-EGFP rat model will contribute to the advancement of lymphatic research as a valuable experimental resource.

PurposeThe primary purpose of the current study was to examine how the presence of two digital ad features – an ad skip option and an ad time display, representing behavioral and cognitive control, respectively – might influence viewer response to in-stream video ads in terms of perceived control, reactance and advertising outcomes.Design/methodology/approachA 2 (Ad skip option: presence vs. absence) × 2 (Ad time display: presence vs absence) between-subjects experiment was conducted online with 217 participants recruited via Qualtrics.FindingsThe results of the online experiment show that the presence of the ad skip option and ad time display related to a higher level of perceived control, predicting lower ad intrusiveness and ad irritation and more favorable attitude toward the ad.Practical implicationsThe findings confirm that an ad skip option and an ad time display could minimize negative responses to in-stream video ads by increasing perceived control and reducing viewer reactance.Originality/valueThe findings provide empirical evidence that multiple dimensions of control features (i.e. behavioral and cognitive) can increase perceived control and strengthen its impact on advertising outcomes.