This research utilizes big data in investigating the impact of a luxury brand's social media marketing activities on customer engagement. In particular, applying the dual perspective of customer ...engagement, this research examines the influence of focusing on the entertainment, interaction, trendiness, and customization dimensions of a luxury brand's social media activities on customer engagement with brand-related social media content. Using big data retrieved from a 60-month period on Twitter (July 2012 to June 2017), this paper analyzes 3.78 million tweets from the top 15 luxury brands with the highest number of Twitter followers. The results indicate that focusing on the entertainment, interaction, and trendiness dimensions of a luxury brand's social media marketing efforts significantly increases customer engagement, while focusing on the customization dimension does not. The findings have important implications for the design, delivery, and management of social media marketing for luxury brands to engage customers with social media content.
Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to ...understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration.
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•Hypo-innervation of the zebrafish heart impairs heart regeneration•Cholinergic signaling guides myocyte proliferation in zebrafish and neonatal mice•Neonatal mouse vagotomy impairs myocyte proliferation and heart regeneration•Neonatal vagotomy reduces the inflammatory response following heart injury
Mahmoud et al. demonstrate that nerves are required for cardiomyocyte proliferation during both zebrafish and neonatal mouse heart regeneration. The negative effect of hypoinnervation on regeneration can be partially rescued by NRG1 and NGF proteins.
The human heart’s failure to replace ischemia-damaged myocardium with regenerated muscle contributes significantly to the worldwide morbidity and mortality associated with coronary artery disease. ...Remarkably, certain vertebrate species, including the zebrafish, achieve complete regeneration of amputated or injured myocardium through the proliferation of spared cardiomyocytes. Nonetheless, the genetic and cellular determinants of natural cardiac regeneration remain incompletely characterized. Here, we report that cardiac regeneration in zebrafish relies on Notch signaling. Following amputation of the zebrafish ventricular apex, Notch receptor expression becomes activated specifically in the endocardium and epicardium, but not the myocardium. Using a dominant negative approach, we discovered that suppression of Notch signaling profoundly impairs cardiac regeneration and induces scar formation at the amputation site. We ruled out defects in endocardial activation, epicardial activation, and dedifferentiation of compact myocardial cells as causative for the regenerative failure. Furthermore, coronary endothelial tubes, which we lineage traced from preexisting endothelium in wild-type hearts, formed in the wound despite the myocardial regenerative failure. Quantification of myocardial proliferation in Notch-suppressed hearts revealed a significant decrease in cycling cardiomyocytes, an observation consistent with a noncell autonomous requirement for Notch signaling in cardiomyocyte proliferation. Unexpectedly, hyperactivation of Notch signaling also suppressed cardiomyocyte proliferation and heart regeneration. Taken together, our data uncover the exquisite sensitivity of regenerative cardiomyocyte proliferation to perturbations in Notch signaling.
Correlative evidence suggests that polyploidization of heart muscle, which occurs naturally in post-natal mammals, creates a barrier to heart regeneration. Here, we move beyond a correlation by ...demonstrating that experimental polyploidization of zebrafish cardiomyocytes is sufficient to suppress their proliferative potential during regeneration. Initially, we determined that zebrafish myocardium becomes susceptible to polyploidization upon transient cytokinesis inhibition mediated by dominant-negative Ect2. Using a transgenic strategy, we generated adult animals containing mosaic hearts composed of differentially labeled diploid and polyploid-enriched cardiomyocyte populations. Diploid cardiomyocytes outcompeted their polyploid neighbors in producing regenerated heart muscle. Moreover, hearts composed of equivalent proportions of diploid and polyploid cardiomyocytes failed to regenerate altogether, demonstrating that a critical percentage of diploid cardiomyocytes is required to achieve heart regeneration. Our data identify cardiomyocyte polyploidization as a barrier to heart regeneration and suggest that mobilizing rare diploid cardiomyocytes in the human heart will improve its regenerative capacity.
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•Cardiomyocytes in adult zebrafish are predominantly mononucleated and diploid•Transient inhibition of Ect2 induces polyploidization of zebrafish cardiomyocytes•Diploid cardiomyocytes outcompete polyploid cardiomyocytes during heart regeneration•Hearts composed of >45% polyploid cardiomyocytes fail to regenerate
It remains unclear why certain non-mammalian species efficiently regenerate their hearts while mammals fail in this endeavor. González-Rosa et al. demonstrate that simply increasing the DNA content of the highly regenerative zebrafish myocardium, to more closely resemble that in mammals, is sufficient to dampen cardiomyocyte proliferative capacity and organ regeneration.
Various human malignancies are characterized by excessive activation of the Janus family of cytoplasmic tyrosine kinases (JAK) and their associated transcription factors STAT3 and STAT5. In the ...majority of solid tumors, this occurs in response to increased abundance of inflammatory cytokines in the tumor microenvironment prominently produced by infiltrating innate immune cells. Many of these cytokines share common receptor subunits and belong to the interleukin (IL)-6/IL-11, IL-10/IL-22 and IL-12/IL-23 families. Therapeutic inhibition of the JAK/STAT3 pathway potentially offers considerable benefit owing to the capacity of JAK/STAT3 signaling to promote cancer hallmarks in the tumor and its environment, including proliferation, survival, angiogenesis, tumor metabolism while suppressing antitumor immunity. This is further emphasized by the current successful clinical applications of JAK-specific small molecule inhibitors for the treatment of inflammatory disorders and hematopoietic malignancies. Here we review current preclinical applications for JAK inhibitors for the treatment of solid cancers in mice, with a focus on the most common malignancies emanating from oncogenic transformation of the epithelial mucosa in the stomach and colon. Emerging data with small molecule JAK-specific adenosine triphosphate-binding analogs corroborate genetic findings and suggest that interference with the JAK/STAT3 pathway may suppress the growth of the most common forms of sporadic colon cancers that arise from mutations of the APC tumor suppressor gene. Likewise inhibition of cytokine-dependent activation of the JAK/STAT3 pathway may also afford orthogonal treatment opportunities for other oncogene-addicted cancer cells that have gained drug resistance.
While the d(0) transition-metal POMs of Group V (V(5+), Nb(5+), Ta(5+)) and Group VI (Mo(6+), W(6+)) have been known for more than a century, the actinyl peroxide POMs, specifically those built of ...uranyl triperoxide or uranyl dihydroxidediperoxide polyhedra, were only realized within the last decade. While virtually every metal on the Periodic Table can form discrete clusters of some type, the actinyls are the only-in addition to the transition-metal POMs- whose chemistry is dictated by the prevalence of the 'yl' oxygen ligand. Thus this emerging structural, solution, and computational chemistry of actinide POMs warrants comparison to the mature chemistry of transition-metal POMs. This assessment between the transition-metal POMs and actinyl POMs (uranyl peroxide POMs, specifically) has provided much insight to the similarities and differences between these two chemistries. We further break down the comparison between the alkaline POMs of Nb and Ta; and the acidic POMs of V, Mo and W. This more indepth literature review and discussion reveals that while an initial evaluation suggests the actinyl POMs are more akin to the alkaline transition-metal POMs, they actually share characteristics unique to the acidic POMs as well. This tutorial review is meant to provide fodder for deriving new POM chemistries of both the familiar transition-metals and the emerging actinides, as well as fostering communication and collaboration between the two scientific communities.
Previous studies demonstrate that the regenerative zebrafish heart responds to injury by upregulating Notch receptors in the endocardium and epicardium. Moreover, global suppression of Notch activity ...following injury impairs cardiomyocyte proliferation and induces scarring. However, the lineage-specific requirements for Notch signaling and full array of downstream targets remain unidentified. Here, we demonstrate that inhibition of endocardial Notch signaling following ventricular amputation compromises cardiomyocyte proliferation and stimulates fibrosis. RNA sequencing uncovered reduced levels of two transcripts encoding secreted Wnt antagonists, Wif1 and Notum1b, in Notch-suppressed hearts. Like Notch receptors, wif1 and notum1b are induced following injury in the endocardium and epicardium. Small-molecule-mediated activation of Wnt signaling is sufficient to impair cardiomyocyte proliferation and induce scarring. Last, Wnt pathway suppression partially restored cardiomyocyte proliferation in hearts experiencing endocardial Notch inhibition. Taken together, our data demonstrate that Notch signaling supports cardiomyocyte proliferation by dampening myocardial Wnt activity during zebrafish heart regeneration.
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•EC Notch signaling is required for regenerative cardiomyocyte proliferation.•EC Notch augments expression of secreted Wnt antagonists notum1b and wif1.•Hyperactivated Wnt signaling suppresses regenerative cardiomyocyte proliferation.•Wnt inhibition boosts cardiomyocyte proliferation in EC Notch-suppressed hearts.
The highly regenerative zebrafish heart responds to injury by upregulating Notch receptors in the endocardium and epicardium to support myocardial proliferation and regeneration. Zhao et al. demonstrate that endocardial (EC) Notch signaling augments the expression of secreted endocardial Wnt antagonists that dampen myocardial Wnt signaling to support regenerative cardiomyocyte renewal.
Nuclear Fuel in a Reactor Accident Burns, Peter C.; Ewing, Rodney C.; Navrotsky, Alexandra
Science (American Association for the Advancement of Science),
03/2012, Letnik:
335, Številka:
6073
Journal Article
Recenzirano
Nuclear accidents that lead to melting of a reactor core create heterogeneous materials containing hundreds of radionuclides, many with short half-lives. The long-lived fission products and ...transuranium elements within damaged fuel remain a concern for millennia. Currently, accurate fundamental models for the prediction of release rates of radionuclides from fuel, especially in contact with water, after an accident remain limited. Relatively little is known about fuel corrosion and radionuclide release under the extreme chemical, radiation, and thermal conditions during and subsequent to a nuclear accident. We review the current understanding of nuclear fuel interactions with the environment, including studies over the relatively narrow range of geochemical, hydrological, and radiation environments relevant to geological repository performance, and discuss priorities for research needed to develop future predictive models.
Fibroblasts are a dynamic cell type that achieve selective differentiated states to mediate acute wound healing and long-term tissue remodeling with scarring. With myocardial infarction injury, ...cardiomyocytes are replaced by secreted extracellular matrix proteins produced by proliferating and differentiating fibroblasts. Here, we employed 3 different mouse lineage-tracing models and stage-specific gene profiling to phenotypically analyze and classify resident cardiac fibroblast dynamics during myocardial infarction injury and stable scar formation. Fibroblasts were activated and highly proliferative, reaching a maximum rate within 2 to 4 days after infarction injury, at which point they expanded 3.5-fold and were maintained long term. By 3 to 7 days, these cells differentiated into myofibroblasts that secreted abundant extracellular matrix proteins and expressed smooth muscle α-actin to structurally support the necrotic area. By 7 to 10 days, myofibroblasts lost proliferative ability and smooth muscle α-actin expression as the collagen-containing extracellular matrix and scar fully matured. However, these same lineage-traced initial fibroblasts persisted within the scar, achieving a new molecular and stable differentiated state referred to as a matrifibrocyte, which was also observed in the scars of human hearts. These cells express common and unique extracellular matrix and tendon genes that are more specialized to support the mature scar.
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