Gregorymygind7609

Chronic pain is a major health problem and the effective treatment for chronic pain is still lacking. The recent crisis created by the overuse of opioids for pain treatment has clearly shown the need for non-addictive novel pain medicine. Conventional pain medicines usually inhibit peripheral nociceptive transmission and reduce central transmission, especially pain-related excitatory transmission. For example, both opioids and gabapentin produce analgesic effects by inhibiting the release of excitatory transmitters and reducing neuronal excitability. Here, we will review recent studies of central synaptic plasticity contributing to central sensitization in chronic pain. Neuronal selective adenylyl cyclase subtype 1 (AC1) is proposed to be a key intracellular protein that causes both presynaptic and postsynaptic forms of long-term potentiation (LTP). Inhibiting the activity of AC1 by selective inhibitor NB001 blocks behavioral sensitization and injury-related anxiety in animal models of chronic pain. We propose that inhibiting injury-related LTPs will provide new mechanisms for designing novel medicines for the treatment of chronic pain and its related emotional disorders.

Two class I TCP transcription factors are required for an efficient elongation of hypocotyls in response to auxin and for the correct expression of a subset of auxin-inducible genes In this work, we analyzed the response to auxin of plants with altered function of the class I TEOSINTE BRANCHED 1, CYCLOIDEA, PCF (TCP) transcription factors TCP14 and TCP15. Several SMALL AUXIN UP RNA (SAUR) genes showed decreased expression in mutant plants defective in these TCPs after an increase in ambient temperature to 29°C, a condition that causes an increase in endogenous auxin levels. Overexpression of SAUR63 caused a more pronounced elongation response in the mutant than in the wild-type at 29°C, suggesting that the decreased expression of SAUR genes is partly responsible for the defective elongation at warm temperature. Notably, several SAUR genes and the auxin response gene IAA19 also showed reduced expression in the mutant after auxin treatment, while the expression of other SAUR genes and of IAA29 was not affectets of the AUXIN RESPONSE FACTOR 6 are regulated by TCP15 and often contain putative TCP recognition motifs in their promoters. JHRE06 Furthermore, we demonstrated that several among them are recognized by TCP15 in vivo. Our results indicate that TCP14 and TCP15 are required for an efficient elongation response to auxin, most likely by regulating a subset of auxin inducible genes related to cell expansion.Prostate cancer (PC) is the most common reproductive cancer in men and the third leading cause of cancer death among men worldwide. Recently targeted therapy showed a significant therapeutic effect on PC, whereas finding more PC therapeutic target is still urgently needed. Melanoma-associated antigen-encoding C2 (MAGE-C2/CT10), which have significant homology with the MAGE-C1/CT-7 gene, was known to be involved in the development of a variety of tumors. However, the role and mechanism of MAGE-C2/CT10 in prostate cancer remains unclear. Herein, we found the high levels of MAGE-C2/CT10 in highly metastatic prostate cancer. Our findings confirmed that the depletion of MAGE-C2/CT10 suppressed the growth of PC cells, and restrained PC cell migration and invasion in vitro. We noticed MAGE-C2/CT10 could stimulate c-Myc expression via FBP1, and further contributed to PC cell proliferation and motility. Performing in vivo assays, we demonstrated MAGE-C2/CT10 promoted tumor growth and metastasis of PC cells in mice. Collectively, we found the abnormal expression of MAGE-C2/CT10 in PC, and revealed the regulatory mechanism underlying MAGE-C2/CT10 promoting PC progression and metastasis.Tumor dissemination into the surrounding stroma is the initial step in a metastatic cascade. Invasion into stroma is a non-autonomous process for cancer, and its progression depends upon the stage of cancer, as well as the cells residing in the stroma. However, a systems framework to understand how stromal fibroblasts resist, collude, or aid cancer invasion has been lacking, limiting our understanding of the role of stromal biology in cancer metastasis. We and others have shown that gene perturbation in stromal fibroblasts can modulate cancer invasion into the stroma, highlighting the active role stroma plays in regulating its own invasion. However, cancer invasion into stroma is a complex higher-order process and consists of various sub-phenotypes that together can result in an invasion. Stromal invasion exhibits a diversity of modalities in vivo. It is not well understood if these diverse modalities are correlated, or they emanate from distinct mechanisms and if stromal biology could regulate these characte the complex interplay between cancer and stromal fibroblasts.This study explored developmental differences in the effects of event rate, temporal expectancy, and sensory modality on continuous performance. Children (ages 7-8 years) and college-aged adults completed visual and auditory continuous performance tasks (CPTs) that were equated at an intermediate (20 events/min) rate using the perceptual sensitivity index (d') and then were compared at faster (40 events/min) and slower (10 events/min) rates to determine the influence of event rate on continuous performance of children and adults. To investigate the effects of temporal expectancy, 20% of the critical signals and neutral events occurred early or late relative to the regular rhythm of the task. The findings (a) suggest that event rate influences continuous performance differently for children and adults, (b) highlight the role of temporal expectancy in continuous performance, and (c) reveal differences in the effects of event rate and temporal expectancy on visual and auditory continuous performance.Correctly assessing the emotional state of others is a crucial part of social interaction. While facial expressions provide much information, faces are often not viewed in isolation, but occur with concurrent sounds, usually voices, which also provide information about the emotion being portrayed. Many studies have examined the crossmodal processing of faces and sounds, but results have been mixed, with different paradigms yielding different results. Using a psychophysical adaptation paradigm, we carried out a series of four experiments to determine whether there is a perceptual advantage when faces and voices match in emotion (congruent), versus when they do not match (incongruent). We presented a single face and a crowd of voices, a crowd of faces and a crowd of voices, a single face of reduced salience and a crowd of voices, and tested this last condition with and without attention directed to the emotion in the face. While we observed aftereffects in the hypothesized direction (adaptation to faces conveying positive emotion yielded negative, contrastive, perceptual aftereffects), we only found a congruent advantage (stronger adaptation effects) when faces were attended and of reduced salience, in line with the theory of inverse effectiveness.