Object-based attention is accentuated by object reward association

Humans use selective attention to prioritize visual features, like color or shape, as well as discrete spatial locations, and these effects are sensitive to the experience of reward. Reward-associated features and locations are accordingly prioritized from early in the visual hierarchy. Attention is also sensitive to the establishment of visual objects: selection of one constituent object part often leads to prioritization of other locations on that object. But very little is known about the influence of reward on this object-based control of attention. Here we show in four experiments that reward prioritization and object prioritization interact in visual cognition to guide selection. Experiment 1 establishes groundwork for this investigation, showing that reward feedback does not negate object prioritization. In Experiment 2, we corroborate the hypothesis that reward prioritization and object prioritization emerge concurrently. In Experiment 3, we find that reward prioritization and object prioritization sustain and interact in extinction, when reward feedback is discontinued. We verify this interaction in Experiment 4, linking it to task experience rather than the strategic utility of the reward association. Results suggest that information gathered from locations on reward-associated objects gains preferential access to cognition. (PsycInfo Database Record (c) 2024 APA, all rights reserved).</p

The Platelet-derived Growth Factor Controls c-myc Expression through a JNK- and AP-1-dependent Signaling Pathway *

Pro-inflammatory cytokines, environmental stresses, as well as receptor tyrosine kinases regulate the activity of JNK. In turn, JNK phosphorylates Jun members of the AP-1 family of transcription factors, thereby controlling processes as different as cell growth, differentiation, and apoptosis. Still, very few targets of the JNK-Jun pathway have been identified. Here we show that JNK is required for the induction of c-myc expression by PDGF. Furthermore, we identify a phylogenetically conserved AP-1-responsive element in the promoter of the c-myc proto-oncogene that recruits in vivo the c-Jun and JunD AP-1 family members and controls the PDGF-dependent transactivation of the c-myc promoter. These findings suggest the existence of a novel biochemical route linking tyrosine kinase receptors, such as those for PDGF, and c-myc expression through JNK activation of AP-1 transcription factors. They also provide a novel potential mechanism by which both JNK and Jun proteins may exert either their proliferative or apoptotic potential by stimulating the expression of the c-myc proto-oncogene

Low-level visual information is maintained across saccades, allowing for a postsaccadic hand-off between visual areas

Experience seems continuous and detailed despite saccadic eye movements changing retinal input several times per second. There is debate whether neural signals related to updating across saccades contain information about stimulus features, or only location pointers without visual details. We investigated the time course of low-level visual information processing across saccades by decoding spatial frequency of a stationary stimulus that changed from one visual hemifield to the other due to a horizontal saccadic eye movement. We recorded magnetoencephalography while human subjects (both sexes) monitored the orientation of a grating stimulus, making spatial frequency task-irrelevant. Separate trials, in which subjects maintained fixation, were used to train a classifier, whose performance was then tested on saccade trials. Decoding performance showed that spatial frequency information of the presaccadic stimulus remained present for ∼200 ms after the saccade, transcending retinotopic specificity. Postsaccadic information ramped up rapidly after saccade offset. There was an overlap of over 100 ms during which decoding was significant from both pre- and postsaccadic processing areas. This suggest that the apparent richness of perception across saccades may be supported by the continuous availability of low-level information with a "soft hand-off" of information during the initial processing sweep of the new fixation. Saccades create frequent discontinuities in visual input, yet perception appears stable and continuous. How is this discontinuous input processed resulting in visual stability? Previous studies have focused on presaccadic remapping. Here we examined the time course of processing of low-level visual information (spatial frequency) across saccades with magnetoencephalography. The results suggest that spatial frequency information is not predictively remapped but also not discarded. Instead, they suggest a soft hand-off over time between different visual areas, making this information continuously available across the saccade. Information about the presaccadic stimulus remains available, while the information about the postsaccadic stimulus has also become available. The simultaneous availability of both the pre and postsaccadic information could enable rich and continuous perception across saccades

UCbase & miRfunc: a database of ultraconserved sequences and microRNA function

Four hundred and eighty-one ultraconserved sequences (UCRs) longer than 200 bases were discovered in the genomes of human, mouse and rat. These are DNA sequences showing 100% identity among the three species. UCRs are frequently located at genomic regions involved in cancer, differentially expressed in human leukemias and carcinomas and in some instances regulated by microRNAs (miRNAs). Here we present UCbase & miRfunc, the first database which provides ultraconserved sequences data and shows miRNA function. Also, it links UCRs and miRNAs with the related human disorders and genomic properties. The current release contains over 2000 sequences from three species (human, mouse and rat). As a web application, UCbase & miRfunc is platform independent and it is accessible at http://microrna.osu.edu/.UCbase4

Invasion of ovarian cancer cells is induced by PITX2-mediated activation of TGF-β and Activin-A

Background:Most ovarian cancers are highly invasive in nature and the high burden of metastatic disease make them a leading cause of mortality among all gynaecological malignancies. The homeodomain transcription factor, PITX2 is associated with cancer in different tissues. Our previous studies demonstrated increased PITX2 expression in human ovarian tumours. Growing evidence linking activation of TGF-β pathway by homeodomain proteins prompted us to look for the possible involvement of this signalling pathway in PITX2-mediated progression of ovarian cancer. Methods: The status of TGF-β signalling in human ovarian tissues was assessed by immunohistochemistry. The expression level of TGFB/INHBA and other invasion-associated genes was measured by quantitative-PCR (Q-PCR) and Western Blot after transfection/treatments with clones/reagents in normal/cancer cells. The physiological effect of PITX2 on invasion/motility was checked by matrigel invasion and wound healing assay. The PITX2- and activin-induced epithelial-mesenchymal transition (EMT) was evaluated by Q-PCR of respective markers and confocal/phase-contrast imaging of cells. Results: Human ovarian tumours showed enhanced TGF-β signalling. Our study uncovers the PITX2-induced expression of TGFB1/2/3 as well as INHBA genes (p < 0.01) followed by SMAD2/3-dependent TGF-β signalling pathway. PITX2-induced TGF-β pathway regulated the expression of invasion-associated genes, SNAI1, CDH1 and MMP9 (p < 0.01) that accounted for enhanced motility/invasion of ovarian cancers. Snail and MMP9 acted as important mediators of PITX2-induced invasiveness of ovarian cancer cells. PITX2 over-expression resulted in loss of epithelial markers (p < 0.01) and gain of mesenchymal markers (p < 0.01) that contributed significantly to ovarian oncogenesis. PITX2-induced INHBA expression (p < 0.01) contributed to EMT in both normal and ovarian cancer cells. Conclusions: Overall, our findings suggest a significant contributory role of PITX2 in promoting invasive behaviour of ovarian cancer cells through up-regulation of TGFB/INHBA. We have also identified the previously unknown involvement of activin-A in promoting EMT. Our work provides novel mechanistic insights into the invasive behavior of ovarian cancer cells. The extension of this study have the potential for therapeutic applications in future

Physicochemical and biological characterization of chitosan-microRNA nanocomplexes for gene delivery to MCF-7 breast cancer cells

Cancer gene therapy requires the design of non-viral vectors that carry genetic material and selectively deliver it with minimal toxicity. Non-viral vectors based on cationic natural polymers can form electrostatic complexes with negatively-charged polynucleotides such as microRNAs (miRNAs). Here we investigated the physicochemical/biophysical properties of chitosan–hsa-miRNA-145 (CS–miRNA) nanocomplexes and the biological responses of MCF-7 breast cancer cells cultured in vitro. Self-assembled CS–miRNA nanocomplexes were produced with a range of (+/−) charge ratios (from 0.6 to 8) using chitosans with various degrees of acetylation and molecular weight. The Z-average particle diameter of the complexes was <200 nm. The surface charge increased with increasing amount of chitosan. We observed that chitosan induces the base-stacking of miRNA in a concentration dependent manner. Surface plasmon resonance spectroscopy shows that complexes formed by low degree of acetylation chitosans are highly stable, regardless of the molecular weight. We found no evidence that these complexes were cytotoxic towards MCF-7 cells. Furthermore, CS–miRNA nanocomplexes with degree of acetylation 12% and 29% were biologically active, showing successful downregulation of target mRNA expression in MCF-7 cells. Our data, therefore, shows that CS–miRNA complexes offer a promising non-viral platform for breast cancer gene therapy