Wnt signaling and tbx16 form a bistable switch to commit bipotential progenitors to mesoderm.

Anterior to posterior growth of the vertebrate body is fueled by a posteriorly located population of bipotential neuro-mesodermal progenitor cells. These progenitors have a limited rate of proliferation and their maintenance is crucial for completion of the anterior-posterior axis. How they leave the progenitor state and commit to differentiation is largely unknown, in part because widespread modulation of factors essential for this process causes organism-wide effects. Using a novel assay, we show that zebrafish Tbx16 (Spadetail) is capable of advancing mesodermal differentiation cell-autonomously. Tbx16 locks cells into the mesodermal state by not only activating downstream mesodermal genes, but also by repressing bipotential progenitor genes, in part through a direct repression of sox2. We demonstrate that tbx16 is activated as cells move from an intermediate Wnt environment to a high Wnt environment, and show that Wnt signaling activates the tbx16 promoter. Importantly, high-level Wnt signaling is able to accelerate mesodermal differentiation cell-autonomously, just as we observe with Tbx16. Finally, because our assay for mesodermal commitment is quantitative we are able to show that the acceleration of mesodermal differentiation is surprisingly incomplete, implicating a potential separation of cell movement and differentiation during this process. Together, our data suggest a model in which high levels of Wnt signaling induce a transition to mesoderm by directly activating tbx16, which in turn acts to irreversibly flip a bistable switch, leading to maintenance of the mesodermal fate and repression of the bipotential progenitor state, even as cells leave the initial high-Wnt environment.

Histoscope: A Web-Based Microscopy Tool for Oral Histology Education.

OBJECTIVES: Histology, the study of tissue structure under a microscope, is one of the most essential yet least engaging topics for health professional students. Understanding tissue microanatomy is crucial for students to be able to recognize cellular structures and follow disease pathogenesis. Traditional histology teaching labs rely on light microscopes and a limited array of slides, which inhibits simultaneous observation by multiple learners, and prevents in-class discussions. We have developed an interactive web-based microscopy tool called "Histoscope" for oral histology in this context. METHODS: Good quality microscope slides were selected for digital scanning. The slides were scanned with multiple layers of z-stacking, a method of taking multiple images at different focal distances. The digital images were checked for quality and were archived on Histoscope. The slides were annotated, and self-assessment questions were prepared for the website. Interactive components were programmed on the website to mimic the experience of using a real light microscope. RESULTS: This web-based tool allows users to interact with histology slides, replicating the experience of observing and manipulating a slide under a real microscope. Through this website, learners can access a broad array of digital oral histology slides and self-assessment questions. CONCLUSIONS: Incorporation of Histoscope in a course can shift traditional teacher-centered histology learning to a collaborative and student-centered learning environment. This platform can also provide students the flexibility to study histology at their own pace.

Mitigating bit flips or single event upsets in epilepsy neurostimulators.

OBJECTIVES: The objective of this study was to review software errors known as single event upsets (SEUs) or bit flips due to cosmic rays in epilepsy neurostimulators. MATERIALS AND METHODS: A case report of a single event upset or bit flip is discussed; device manufacturers and publicly available data were queried for both incidence and types of error as well as strategies of software error mitigation. RESULTS: Neurostimulators, like other implanted devices such as pacemakers, are prone to single event upsets. Strategies for SEU mitigation are reviewed. CONCLUSIONS: Cosmic radiation can threaten RAM and settings of neurostimulators; neuromodulation teams and device designers need to take this threat into account when designing multifunctional neuromodulation systems.