There has been considerable progress in identifying signaling pathways directing the differentiation of human pluripotent stem cells (hPSCs) into specialized cell types including neurons. However, extrinsic factor-based differentiation of hPSCs is a slow, step-wise process mimicking the protracted timing of normal human development. Using a small molecule screen we identified a combination of five small molecule pathway inhibitors sufficient to yield hPSC-derived neurons at >75% efficiency within 10 days of differentiation. The resulting neurons express canonical markers and functional properties of human nociceptors including TTX-resistant, SCN10A-dependent sodium currents and response to nociceptive stimuli including ATP and capsaicin. Neuronal fate acquisition occurs three-fold faster than during in vivo1 development suggesting that use of small molecule pathway inhibitors could develop into a general strategy for accelerating developmental timing in vitro. The quick and high efficiency derivation of nociceptors offers unprecedented access to this medically relevant cell type for studies of human pain.

SUMMARY Cranial placodes are embryonic structures essential for sensory and endocrine organ development. Human placode development has remained largely inaccessible despite the serious medical conditions caused by the dysfunction of placode-derived tissues. Here, we demonstrate the efficient derivation of cranial placodes from human pluripotent stem cells. Timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Concomitant inhibition of FGF signaling disrupts placode derivation and induces surface ectoderm. Further fate specification at the pre-placode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers and anterior pituitary hormone-producing cells that upon transplantation produce human GH and ACTH in vivo. Our results establish a powerful experimental platform to study human cranial placode development and set the stage for the development of human cell-based therapies in sensory and endocrine disease.

In December 2013, 16 teams from around the world gathered at Homestead Speedway near Miami, FL to participate in the DARPA Robotics Challenge (DRC) Trials, an aggressive robotics competition partly inspired by the aftermath of the Fukushima Daiichi reactor incident. While the focus of the DRC Trials is to advance robotics for use in austere and inhospitable environments, the objectives of the DRC are to progress the areas of supervised autonomy and mobile manipulation for everyday robotics. NASA's Johnson Space Center led a team comprised of numerous partners to develop Valkyrie, NASA's first bipedal humanoid robot. Valkyrie is a 44 degree‐of‐freedom, series elastic actuator‐based robot that draws upon over 18 years of humanoid robotics design heritage. Valkyrie's application intent is aimed at not only responding to events like Fukushima, but also advancing human spaceflight endeavors in extraterrestrial planetary settings. This paper presents a brief system overview, detailing Valkyrie's mechatronic subsystems, followed by a summarization of the inverse kinematics‐based walking algorithm employed at the Trials. Next, the software and control architectures are highlighted along with a description of the operator interface tools. Finally, some closing remarks are given about the competition, and a vision of future work is provided.

Analysis of Sox17 mutant mice reveals that gap junction coupling across the gut endoderm of the embryo transmits the left-right asymmetric signal from the node to the site of asymmetric organogenesis in mice.

Background/Aims: RNF43 is a member of transmembrane E3 ubiquitin ligases and plays important roles in tumor formation progression. In current study, we aimed to explore RNF43 expression and analyze its role in gastric carcinoma. Methods and Results: The level of RNF43 was detected in 77 cases of gastric carcinoma and matched normal tissues by real-time PCR, western blotting and immunohistochemistry. We found that the expression of RNF43 was significantly down-regulated in the gastric carcinoma tissues compared to the normal mucosae (all P<0.001). In addition, RNF43 was significantly correlated with histological differentiation (P = 0.001), T-stage cancer (P<0.001), depth of invasion (P<0.001), metastasis of regional lymph nodes (P<0.001), pTNM stage (P<0.001) and survival (P = 0.021). We further explored the biological functions of RNF43 in gastric carcinoma cell lines. Both gain- and loss-function assays show that RNF43 could suppress cell proliferation while promotes cell apoptosis. Further, we found that RNF43 was positively correlated with p53 and cleaved-caspase3 and negatively correlated with Ki67 and Lgr5. Concolusion: In conclusion, RNF43 might act as a tumor suppressor in gastric carcinoma and might be a potential indicator for the clinical assessment of gastric cancer prognosis