Fibroma of tendon sheath located within the ankle joint capsule

We report a very rare case of fibroma of the tendon sheath arising from the anteromedial ankle joint capsule, with no apparent connection to any tendon in the area, found in a 58-year-old patient complaining of progressive local swelling. This uncommon tumor has its usual localization in tendon sheaths, is extremely rare in joint capsules, and has never been described in this location previously. MRI showed nonuniform low signal intensity in T1- and T2-weighted images and high intensity in STIR images. The mass was completely excised by open surgery. Histopathological analysis later confirmed the diagnosis of a fibroma of the tendon sheath

A dopaminergic switch for fear to safety transitions

Overcoming aversive emotional memories requires neural systems that detect when fear responses are no longer appropriate. The midbrain ventral tegmental area (VTA) dopamine system has been implicated in reward and more broadly in signalling when a better than expected outcome has occurred. This suggests that it may be important in guiding fear to safety transitions. We report that when an expected aversive outcome does not occur, activity in midbrain dopamine neurons is necessary to extinguish behavioral fear responses and engage molecular signalling events in extinction learning circuits. Furthermore, a specific dopamine projection to the nucleus accumbens medial shell is partially responsible for this effect. By contrast, a separate dopamine projection to the medial prefrontal cortex opposes extinction learning. This demonstrates a novel function for the canonical VTA-dopamine reward system and reveals opposing behavioural roles for different dopamine neuron projections in fear extinction learning

Epitaxial lateral overgrowth of α-Ga2O3 by halide vapor phase epitaxy

We demonstrate the epitaxial lateral overgrowth of α-Ga2O3 by halide vapor phase epitaxy. We prepared patterned SiO2 masks on a (0001) α-Ga2O3/sapphire template, and then α-Ga2O3 islands were regrown selectively on the mask windows. The islands grew vertically and laterally to coalesce with each other. Facet control of the α-Ga2O3 islands was achieved by controlling the growth temperature, and inclined facets developed by decreasing the temperature. Transmission electron microscopy revealed that the crystal quality of the regrown α-Ga2O3 was improved owing to both the blocking of dislocations by the mask and the dislocation bending by the inclined facets

Nodes-and-connections RNAi knockdown screening: identification of a signaling molecule network involved in fulvestrant action and breast cancer prognosis

Although RNA interference (RNAi) knockdown screening of cancer cell cultures is an effective approach to predict drug targets or therapeutic/prognostic biomarkers, interactions among identified targets often remain obscure. Here, we introduce the nodes-and-connections RNAi knockdown screening that generates a map of target interactions through systematic iterations of in silico prediction of targets and their experimental validation. An initial RNAi knockdown screening of MCF-7 human breast cancer cells targeting 6560 proteins identified four signaling molecules required for their fulvestrant-induced apoptosis. Signaling molecules physically or functionally interacting with these four primary node targets were computationally predicted and experimentally validated, resulting in identification of four second-generation nodes. Three rounds of further iterations of the prediction–validation cycle generated third, fourth and fifth generation of nodes, completing a 19-node interaction map that contained three predicted nodes but without experimental validation because of technical limitations. The interaction map involved all three members of the death-associated protein kinases (DAPKs) as well as their upstream and downstream signaling molecules (calmodulins and myosin light chain kinases), suggesting that DAPKs play critical roles in the cytocidal action of fulvestrant. The in silico Kaplan–Meier analysis of previously reported human breast cancer cohorts demonstrated significant prognostic predictive power for five of the experimentally validated nodes and for three of the prediction-only nodes. Immunohistochemical studies on the expression of 10 nodal proteins in human breast cancer tissues not only supported their prognostic prediction power but also provided statistically significant evidence of their synchronized expression, implying functional interactions among these nodal proteins. Thus, the Nodes-and-Connections approach to RNAi knockdown screening yields biologically meaningful outcomes by taking advantage of the existing knowledge of the physical and functional interactions between the predicted target genes. The resulting interaction maps provide useful information on signaling pathways cooperatively involved in clinically important features of the malignant cells, such as drug resistance