Varieties of perceptual instability and their neural correlates.

We report experiments designed to learn whether different kinds of perceptually unstable visual images engage different neural mechanisms. 21 subjects viewed two types of bi-stable images while we scanned the activity in their brains with functional magnetic resonance imaging (fMRI); in one (intra-categorical type) the two percepts remained within the same category (e.g. face-face) while in the other (cross-categorical type) they crossed categorical boundaries (e.g. face-body). The results showed that cross- and intra-categorical reversals share a common reversal-related neural circuitry, which includes fronto-parietal cortex and primary visual cortex (area V1). Cross-categorical reversals alone engaged additional areas, notably anterior cingulate cortex and superior temporal gyrus, which have been posited to be involved in conflict resolution

Quantifying the If, the When, and the What of the Sublime: A Survey and Latent Class Analysis of Incidence, Emotions, and Distinct Varieties of Personal Sublime Experiences

Sublime encounters provide a compelling example of the peaks of our shared emotional and cognitive experiences. For centuries, these have been a target for philosophy and, more recently, for psychology, with its renewed focus on profound or aesthetic events. The sublime has been theoretically connected to multiple contexts, from interactions with overpowering nature, to beauty, music, even interpersonal engagements, and to multiple emotions—danger, awe, pleasure, fear—often with diametrically opposing arguments for what constitutes these events. However, despite this prolonged discussion, there is still a scarcity of actual systematic research. It is not known whether sublime encounters are common, nor how they are described by individuals, or if reports match theoretical arguments: Are there one or more, or no, distinct sublime types? We address these questions by matching historical discussions to 402 participants’ (Western adults) reports of whether they have ever experienced the sublime and, if so, how these are described in terms of cognitive/emotional and contextual factors. Roughly half reported having had at least one sublime experience, with accounts involving a range of contexts that essentially cover the full spectrum of past theoretical arguments. At the same time, when we considered the cognitive/affective descriptions using network science and latent class analysis of reported feelings, 90.8% fit one model, with involved communities (or interrelated clusters) of positive emotions, discrepancy, self-awareness, transformation/insight, and, notably, not including negative emotions/fear. We conclude with a discussion of how this approach and findings might be used as a basis for considering sublime theory and shaping future research

The NeuroDante Project: Neurometric measurements of participant’s reaction to literary auditory stimuli from dante’s “divina commedia”

Neurodante. Progetto di analisi neurometrica di alcuni brani della Commedi

Alendronate-induced disruption of actin cytoskeleton and inhibition of migration/invasion are associated with cofilin downregulation in PC-3 prostate cancer cells

Bisphosphonates are used for prevention of osteoporosis and metastatic bone diseases. Anti-invasive effects on various cancer cells have also been reported, but the mechanisms involved are not well-understood. We investigated the effects of the nitrogen-containing bisphosphonate alendronate (ALN) on the regulation of actin cytoskeleton in PC-3 cells. We analyzed the ALN effect on the organization and the dynamics of actin, and on the cytoskeleton-related regulatory proteins cofilin, p21-associated kinase 2 (PAK2), paxillin and focal adhesion kinase. Immunostainings of cofilin in ALN-treated PC-3 cells and xenografts were performed, and the role of cofilin in ALN-regulated F-actin organization and migration/invasion in PC-3 cells was analyzed using cofilin knockdown and transfection. We demonstrate that disrupted F-actin organization and decreased cell motility in ALN-treated PC-3 cells were associated with decreased levels of total and phosphorylated cofilin. PAK2 levels were also lowered but adhesion-related proteins were not altered. The knockdown of cofilin similarly impaired F-actin organization and decreased invasion of PC-3 cells, whereas in the cells transfected with a cofilin expressing vector, ALN treatment did not decrease cellular cofilin levels and migration as in mock transfected cells. ALN also reduced immunohistochemical staining of cofilin in PC-3 xenografts. Our results suggest that reduction of cofilin has an important role in ALN-induced disruption of the actin cytoskeleton and inhibition of the PC-3 cell motility and invasion. These data also support the idea that the nitrogen-containing bisphosphonates could be efficacious in inhibition of prostate cancer invasion and metastasis, if delivered in a pharmacological formulation accessible to the tumors.</p

Expression of chemokine receptors on peripheral blood lymphocytes in multiple sclerosis and neuromyelitis optica

<p>Abstract</p> <p>Background</p> <p>The role of different chemokine receptors in the pathogenesis of multiple sclerosis (MS) has been extensively investigated; however, little is known about the difference in the role of chemokine receptors between the pathogenesis of neuromyelitis optica (NMO) and MS. Therefore, we examined the expression of chemokine receptors on peripheral blood lymphocytes (PBL) in MS and NMO.</p> <p>Methods</p> <p>We used flow cytometry to analyse lymphocyte subsets in 12 patients with relapsing NMO, 24 with relapsing-remitting MS during relapse, 3 with NMO and 5 with MS during remission.</p> <p>Results</p> <p>Compared with healthy controls (HC), the percentage of lymphocytes in white blood cells was significantly lower in NMO and MS patients. The percentage of T cells expressing CD4⁺CD25⁺and CD4⁺CD45RO⁺was higher, while that of CD4⁺CC chemokine receptor (CCR)3⁺(T helper 2, Th2) was significantly lower in MS patients than in HC. The ratios of CD4⁺CXC chemokine receptors (CXCR)3⁺/CD4⁺CCR3⁺(Th1/Th2) and CD8⁺CXCR3⁺/CD8⁺CCR4⁺(T cytotoxic 1, Tc1/Tc2) were higher in MS patients than in HC. The percentage of CD8⁺CXCR3⁺T cell (Tc1) and CD4⁺CXCR3⁺T cell (Th1) decreased significantly during remission in MS patients (<it>P <</it>0.05). No significant differences were identified in the expression of the chemokine receptors on PBL in NMO patients compared with MS patients and HC.</p> <p>Conclusions</p> <p>Th1 dominance of chemokine receptors on blood T cells and the correlation between CXCR3⁺T cell (Th1 and Tc1) and disease activity in MS patients were confirmed by analysing chemokines receptors on PBL. In contrast, deviation in the Th1/Th2 balance was not observed in NMO patients.</p

Effects of Different Exercise Training Protocols on Gene Expression of Rac1 and PAK1 in Healthy Rat Fast- and Slow-Type Muscles

Purpose Rac1 and its downstream target PAK1 are novel regulators of insulin and exercise-induced glucose uptake in skeletal muscle. However, it is not yet understood how different training intensities affect the expression of these proteins. Therefore, we studied the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on Rac1 and PAK1 expression in fast-type (gastrocnemius, GC) and slow-type (soleus, SOL) muscles in rats after HIIT and MICT swimming exercises. Methods The mRNA expression was determined using qPCR and protein expression levels with reverse-phase protein microarray (RPPA). Results HIIT significantly decreased Rac1 mRNA expression in GC compared to MICT (p = 0.003) and to the control group (CON) (p = 0.001). At the protein level Rac1 was increased in GC in both training groups, but only the difference between HIIT and CON was significant (p = 0.02). HIIT caused significant decrease of PAK1 mRNA expression in GC compared to MICT (p = 0.007) and to CON (p = 0.001). At the protein level, HIIT increased PAK1 expression in GC compared to MICT and CON (by similar to 17%), but the difference was not statistically significant (p = 0.3, p = 0.2, respectively). There were no significant differences in the Rac1 or PAK1 expression in SOL between the groups. Conclusion Our results indicate that HIIT, but not MICT, decreases Rac1 and PAK1 mRNA expression and increases the protein expression of especially Rac1 but only in fast-type muscle. These exercise training findings may reveal new therapeutic targets to treat patients with metabolic diseases

Toll-like receptor 9 expression is associated with breast cancer sensitivity to the growth inhibitory effects of bisphosphonates in vitro and in vivo

AbstractBisphosphonates are standard treatments for bone metastases. When given in the adjuvant setting, they reduce breast cancer mortality and recurrence in bone but only among post-menopausal patients. Optimal drug use would require biomarker-based patient selection. Such biomarkers are not yet in clinical use. Based on the similarities in inflammatory responses to bisphosphonates and Toll-like receptor (TLR) agonists, we hypothesized that TLR9 expression may affect bisphosphonate responses in cells. We compared bisphosphonate effects in breast cancer cell lines with low or high TLR9 expression. We discovered that cells with decreased TLR9 expression are significantly more sensitive to the growth-inhibitory effects of bisphosphonates in vitro and in vivo. Furthermore, cancer growth-promoting effects seen with some bisphosphonates in some control shRNA cells were not detected in TLR9 shRNA cells. These differences were not associated with inhibition of Rap1A prenylation or p38 phosphorylation, which are known markers for bisphosphonate activity. However, TLR9 shRNA cells exhibited increased sensitivity to ApppI, a metabolite that accumulates in cells after bisphosphonate treatment. We conclude that decreased TLR9-expression sensitizes breast cancer cells to the growth inhibitory effects of bisphosphonates. Our results suggest that TLR9 should be studied as a potential biomarker for adjuvant bisphosphonate sensitivity among breast cancer patients.</div