Epstein-Barr virus (EBV)-associated malignancies, as well as lymphoblastoid cell lines (LCLs), obtained in vitro by EBV infection of B cells, express latent viral proteins and maintain their ability ...to grow indefinitely through inappropriate activation of telomere-specific reverse transcriptase (TERT), the catalytic component of telomerase. Our previous studies demonstrated that high levels of TERT expression in LCLs prevent the activation of EBV lytic cycle, which is instead triggered by TERT silencing. As lytic infection promotes the death of EBV-positive tumor cells, understanding the mechanism(s) by which TERT affects the latent/lytic status of EBV may be important for setting new therapeutic strategies. BATF, a transcription factor activated by NOTCH2, the major NOTCH family member in B cells, negatively affects the expression of BZLF1, the master regulator of viral lytic cycle. We therefore analyzed the interplay between TERT, NOTCH and BATF in LCLs and found that high levels of endogenous TERT are associated with high NOTCH2 and BATF expression levels. In addition, ectopic expression of TERT in LCLs with low levels of endogenous telomerase was associated with upregulation of NOTCH2 and BATF at both mRNA and protein levels. By contrast, infection of LCLs with retroviral vectors expressing functional NOTCH2 did not alter TERT transcript levels. Luciferase reporter assays, demonstrated that TERT significantly activated NOTCH2 promoter in a dose-dependent manner. We also found that NF-κB pathway is involved in TERT-induced NOTCH2 activation. Lastly, pharmacologic inhibition of NOTCH signaling triggers the EBV lytic cycle, leading to the death of EBV-infected cells. Overall, these results indicate that TERT contributes to preserve EBV latency in B cells mainly through the NOTCH2/BAFT pathway, and suggest that NOTCH2 inhibition may represent an appealing therapeutic strategy against EBV-associated malignancies.
Flow cytometry allows an easy quantitation of reactive oxygen intermediate production and of C3bi receptor expression by granulocytes, thus providing a clinical tool to evaluate the ...hemodialysis-related granulocyte activation. In this flowcytometric study, we analyzed the effects of cellulosic, synthetic polyacrylonitrile, and ethylene-vinyl-alcohol dialyzers on granulocyte membrane and function. Our results confirmed the data reported in the literature on granulocyte activation secondary to cellulosic membranes and the better biocompatibility of synthetic dialyzers that did not increase C3bi receptor expression and reactive oxygen intermediate generation by granulocytes. The flow-cytometric analysis of granulocyte activation might be the method of choice to identify the best patient/membrane interaction in every single patient.
•Yawn contagion and play face mimicry are found in human and non-human animals.•In humans facial muscle contraction has a causal effect on brain emotion generation.•Mimicry phenomena highlight a ...correlative link between bodily and emotional states.•This link, found in animals, may be evolutionarily more ancient than expected.•A shared approach is proposed for research on human and non-human animals.
Spontaneous mimicry appears fundamental to emotional perception and contagion, especially when it involves facial emotional expressions. Here we cover recent evidence on spontaneous mimicry from ethology, psychology and neuroscience, in non-human and human animals. We first consider how mimicry unfolds in non-human animals (particularly primates) and how it relates to emotional contagion. We focus on two forms of mimicry-related phenomena: facial mimicry and yawn contagion, which are largely conserved across mammals and useful to draw evolutionary scenarios. Next, we expand on the psychological evidence from humans that bears on current theoretical debates and also informs non-human animal research. Finally, we cover the neural bases of facial mimicry and yawn contagion. We move beyond the perception/expression/experience trichotomy and from the correlational to the causal evidence that links facial mimicry to emotional contagion by presenting evidence from neuroimaging, direct manipulation, neuro-stimulation and lesion studies. In conclusion, this review proposes a bottom-up, multidisciplinary approach to the study of spontaneous mimicry that accounts for the evolutionary continuity linking non-human and human animals.
The existence of so-called 'basic emotions' and their defining attributes represents a long lasting and yet unsettled issue in psychology. Recently, neuroimaging evidence, especially related to the ...advent of neuroimaging meta-analytic methods, has revitalized this debate in the endeavor of systems and human neuroscience. The core theme focuses on the existence of unique neural bases that are specific and characteristic for each instance of basic emotion. Here we review this evidence, outlining contradictory findings, strengths and limits of different approaches. Constructionism dismisses the existence of dedicated neural structures for basic emotions, considering that the assumption of a
relationship between neural structures and their functions is central to basic emotion theories. While these critiques are useful to pinpoint current limitations of basic emotions theories, we argue that they do not always appear equally generative in fostering new testable accounts on how the brain relates to affective functions. We then consider evidence beyond PET and fMRI, including results concerning the relation between basic emotions and awareness and data from neuropsychology on patients with focal brain damage. Evidence from lesion studies are indeed particularly informative, as they are able to bring correlational evidence typical of neuroimaging studies to causation, thereby characterizing which brain structures are necessary for, rather than simply related to, basic emotion processing. These other studies shed light on attributes often ascribed to basic emotions, such as automaticity of perception, quick onset, and brief duration. Overall, we consider that evidence in favor of the neurobiological underpinnings of basic emotions outweighs dismissive approaches. In fact, the concept of basic emotions can still be fruitful, if updated to current neurobiological knowledge that overcomes traditional
localization of functions in the brain. In particular, we propose that the structure-function relationship between brain and emotions is better described in terms of pluripotentiality, which refers to the fact that one neural structure can fulfill multiple functions, depending on the functional network and pattern of co-activations displayed at any given moment.
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