The Wnt/beta-catenin/TCF4 pathway plays critical roles in the maintenance of small intestinal epithelium; however, downstream targets of the beta-catenin/TCF4 complex are not extensively characterized. We identified miR-30e as an immediate target activated by the beta-catenin/TCF4 complex. miR-30e was detected in the peri-nuclear region of the intestinal crypt IEC-6 cells. Bioinformatics analysis revealed clustered beta-catenin/TCF4 binding sites within the miR-30e promoter region. This promoter region was cloned into pGL3-control luciferase reporter vector, with the enhancer region removed. Transfection of pCMV-SPORT6-beta-catenin expression vector dose-dependently increased luciferase activity, and co-transfection of pCMV-SPORT6-TCF4 expression vector further enhanced the promoter activity. Dexamethasone-induced IEC-6 cells differentiation caused a 2.5-fold increase in miR-30e expression, and upon beta-catenin siRNA transfection, miR-30e increased 1.3-fold. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay confirmed the binding between beta-catenin/TCF4 complexes from IEC-6 nuclear extracts and the putative sequences in the miR-30e promoter. These results demonstrate that beta-catenin/TCF4 transactivates miR-30e during intestinal cell differentiation.

An adult-like concept of intention includes a deliberate action to achieve a goal and a belief that one's action (if successful) will cause the desired outcome. For example, good outcomes caused by accident or by chance are not believed to be caused intentionally. In two experiments, we asked whether children understand this connection between intentions and outcomes. Children played two games in which actions could produce unintended outcomes (i.e., causes were unplanned). Children sometimes received a desirable reward independent of intention. In Experiment 1, 4- and 5-year-olds mistakenly claimed they had intended the desirable outcome even when it was unexpected. Four-year-olds judged that they had not intended a deliberate action if it did not yield a rewarding outcome. Experiment 2 demonstrates that 6-year-olds seldom make these errors. The results suggest that 4- and 5-year-old children have not yet attained an adult-like concept of intention. Their inaccurate judgments regarding their intentions, given a rewarding yet unexpected outcome, can be explained by a positivity bias. © 2010 Elsevier Inc.

The current study employed a modified gambling task, in which probabilistic cues were provided to elicit positive or negative expectations. Event-related potentials (ERPs) to "final outcome" and "probabilistic cues" were analyzed. Difference waves between the negative condition and the corresponding positive condition were examined. The results confirm that feedback related negativity (FRN) amplitude is modulated by the interaction of outcome valence and expectancy by showing larger FRN difference waves for unexpected than expected outcomes. More interestingly, the difference wave between ERPs elicited by positive and negative expectations showed a negative deflection, with a frontal midline source density around 280 ms after onset of the predictive cue. Negative expectations were associated with larger FRN amplitudes than positive expectations. This suggests that FRN is elicited by probabilistic cues to pending outcomes. © 2011 Society for Psychophysiological Research.

Deleted in liver cancer 1 (DLC1) is a RhoGTPase activation protein-containing tumor suppressor that associates with various types of cancer. Although DLC2 shares a similar domain structure with that of DLC1, the function of DLC2 is not well characterized. Here, we describe the expression and ablation of DLC2 in mice using a reporter-knockout approach. DLC2 is expressed in several tissues and in endothelial cells (ECs) of blood vessels. Although ECs and blood vessels show no histological abnormalities and mice appear overall healthy, DLC2-mutant mice display enhanced angiogenic responses induced by matrigel and by tumor cells. Silencing of DLC2 in human ECs has reduced cell attachment, increased migration, and tube formation. These changes are rescued by silencing of RhoA, suggesting that the process is RhoA pathway dependent. These results indicate that DLC2 is not required for mouse development and normal vessel formation, but may protect mouse from unwanted angiogenesis induced by, for example, tumor cells.

Within the field of glaucoma research, neuroprotection is defined as slowing the functional loss in glaucoma by a mechanism independent of lowering of intraocular pressure. There is currently a great potential for research surrounding neuroprotection as it relates to glaucoma. Anatomical targets for neuroprotection should focus on upstream rather than downstream factors, and could include any part of the retinal ganglion cell, the glia, especially astrocytes or Muller cells, and vasculature. The great number of anatomical targets is exceeded only by the number of possible biochemical pathways and potential treatments. Successful treatment may be accomplished through the targeting of one or even a combination of multiple pathways. Once a treatment is shown effective in vitro, it should be evaluated in vivo with carefully chosen animal models and studied in sufficient numbers to detect statistically and clinically significant effects. Such a drug should have few systemic side effects and its delivery should be optimized so as to encourage compliance. There are still a multitude of possible screens available to test the efficacy of a neuroprotective drug and a single gold standard is ideal for the accurate assessment and comparison of new drugs. Future studies in neuroprotection should investigate the genetic component of the disease, novel pharmaceutical agents for new or known pathways, modulations of scleral biomechanics, and relation to research of other complex disorders of the central nervous system.

The GERmanium Detector Array (Gerda) is a low background experiment located at the Laboratori Nazionali del Gran Sasso in Italy, which searches for neutrinoless double-beta decay of 76 Ge into 76 Se+2e - . Gerda has been conceived in two phases. Phase II, which started in December 2015, features several novelties including 30 new 76Ge enriched detectors. These were manufactured according to the Broad Energy Germanium (BEGe) detector design that has a better background discrimination capability and energy resolution compared to formerly widely-used types. Prior to their installation, the new BEGe detectors were mounted in vacuum cryostats and characterized in detail in the Hades underground laboratory in Belgium. This paper describes the properties and the overall performance of these detectors during operation in vacuum. The characterization campaign provided not only direct input for Gerda Phase II data collection and analyses, but also allowed to study detector phenomena, detector correlations as well as to test the accuracy of pulse shape simulation codes.