A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers

Our results are the first to show the presence of a 3'UTR polymorphism on the V30M haplotype in Swedish carriers, which can serve as a miRNA binding site potentially leading to down-regulated expression from the mutated TTR allele. This finding may be related to the low penetrance and high age at onset of the disease observed in the Swedish patient population

Dissociating Object Directed and Non-Object Directed Action in the Human Mirror System; Implications for Theories of Motor Simulation

Mirror neurons are single cells found in macaque premotor and parietal cortices that are active during action execution and observation. In non-human primates, mirror neurons have only been found in relation to object-directed movements or communicative gestures, as non-object directed actions of the upper limb are not well characterized in non-human primates. Mirror neurons provide important evidence for motor simulation theories of cognition, sometimes referred to as the direct matching hypothesis, which propose that observed actions are mapped onto associated motor schemata in a direct and automatic manner. This study, for the first time, directly compares mirror responses, defined as the overlap between action execution and observation, during object directed and meaningless non-object directed actions. We present functional MRI data that demonstrate a clear dissociation between object directed and non-object directed actions within the human mirror system. A premotor and parietal network was preferentially active during object directed actions, whether observed or executed. Moreover, we report spatially correlated activity across multiple voxels for observation and execution of an object directed action. In contrast to predictions made by motor simulation theory, no similar activity was observed for non-object directed actions. These data demonstrate that object directed and meaningless non-object directed actions are subserved by different neuronal networks and that the human mirror response is significantly greater for object directed actions. These data have important implications for understanding the human mirror system and for simulation theories of motor cognition. Subsequent theories of motor simulation must account for these differences, possibly by acknowledging the role of experience in modulating the mirror response

Salivary mental stress proteins.

Of the major diagnostic specimen types, saliva is one of the most easily collected. Many studies have focused on the evaluation of salivary proteins secreted by healthy people and patients with various diseases during responses to acute mental stress. In particular, such studies have focused on cortisol, α-amylase, chromogranin A (CgA), and immunoglobulin A (IgA) as salivary stress markers. Each of these salivary stress markers has its own strengths and weaknesses as well as data gaps related to many factors including collection technique. In this review, we summarize the critical knowledge of the positive and negative attributes and data gaps pertaining to each salivary stress marker

Investigation of AGE, their receptor and NF-KB activation and apoptosis in patients with ATTR and Gelsolin amyloidosis

Background: Transthyretin (TTR) and gelsolin amyloidoses represent two types of hereditary amyloidosis in which point mutations in the respective protein lead to conformational changes of the protein with subsequent amyloid fibril formation. Material and methods: Tissues from Finnish gelsolin amyloid patients, Danish, Japanese and Swedish ATTR patients were immunostained for AGE, RAGE, NF-κB, PARP, and caspases 3 and 8. Results: Amyloid was heavily deposited in myocard, kidney and gastrointestinal tract of all patients. Immunoreactive areas to AGE and RAGE were detected in the heart, kidney, rectum, gut and appendix. AGE and RAGE were well co-localised with amyloid deposits. In five out of 14 patients neither NF-κB activation nor induction of apoptosis marked by positive immunostaining for NF-κB, PARP, or caspases 3 and 8 was found, and markers of apoptosis were detected in some samples without accompanying NF-κB activation. Conclusion: Our results suggest that both AGE and RAGE may have a common role in evolution of TTR and gelsolin-related amyloidoses. Apart from AGE-RAGE interactions both amyloid proteins may directly bind to RAGE and result in cellular perturbations; but in view of this study cytotoxic effects other than those triggered by activation of NF-κB or apoptosis should be considere

Therapeutic approaches targeting midkine suppress tumor growth and lung metastasis in osteosarcoma

Midkine (MK) plays important roles in tumorigenesis, however, the biological function of MK and whether MK can be a therapeutic target in osteosarcoma are unclear. Here, we found that osteosarcoma tissues showed high MK expression. MK knockdown by small interfering RNA significantly induced apoptosis in osteosarcoma cells, whereas recombinant MK increased cell proliferation. Inhibition of MK signaling by anti-MK monoclonal antibody (anti-MK mAb) suppressed growth of osteosarcoma cells both in vitro and in vivo. Moreover, inhibition of MK function significantly suppressed lung metastasis in xenograft transplantation model. Targeting MK by anti-MK mAb may have value in the treatment of osteosarcoma