Limitations of fluorescent timer protein maturation kinetics to isolate transcriptionally synchronized human neural progenitor cells.

Differentiation of human pluripotent stem cells (hPSCs) into subtype-specific neurons holds substantial potential for disease modeling . For successful differentiation, a detailed understanding of the transcriptional networks regulating cell fate decisions is critical. The heterochronic nature of neurodevelopment, during which distinct cells in the brain and during differentiation acquire their fates in an unsynchronized manner, hinders pooled transcriptional comparisons.

Limitations of fluorescent timer protein maturation kinetics to isolate transcriptionally synchronized cortically differentiating human pluripotent stem cells.

Differentiation of human pluripotent stem cells (hPSC) into distinct neuronal populations holds substantial potential for disease modeling , toward both elucidation of pathobiological mechanisms and screening of potential therapeutic agents. For successful differentiation of hPSCs into subtype-specific neurons using protocols, detailed understanding of the transcriptional networks and their dynamic programs regulating endogenous cell fate decisions is critical. One major roadblock is the heterochronic nature of neurodevelopment, during which distinct cells and cell types in the brain and during differentiation mature and acquire their fates in an unsynchronized manner, hindering pooled transcriptional comparisons.

An unbiased AAV-STARR-seq screen revealing the enhancer activity map of genomic regions in the mouse brain in vivo.

Enhancers are important cis-regulatory elements controlling cell-type specific expression patterns of genes. Furthermore, combinations of enhancers and minimal promoters are utilized to construct small, artificial promoters for gene delivery vectors. Large-scale functional screening methodology to construct genomic maps of enhancer activities has been successfully established in cultured cell lines, however, not yet applied to terminally differentiated cells and tissues in a living animal.

BigNeuron: a resource to benchmark and predict performance of algorithms for automated tracing of neurons in light microscopy datasets.

BigNeuron is an open community bench-testing platform with the goal of setting open standards for accurate and fast automatic neuron tracing. We gathered a diverse set of image volumes across several species that is representative of the data obtained in many neuroscience laboratories interested in neuron tracing. Here, we report generated gold standard manual annotations for a subset of the available imaging datasets and quantified tracing quality for 35 automatic tracing algorithms.

Rapid nucleus-scale reorganization of chromatin in neurons enables transcriptional adaptation for memory consolidation.

The interphase nucleus is functionally organized in active and repressed territories defining the transcriptional status of the cell. However, it remains poorly understood how the nuclear architecture of neurons adapts in response to behaviorally relevant stimuli that trigger fast alterations in gene expression patterns. Imaging of fluorescently tagged nucleosomes revealed that pharmacological manipulation of neuronal activity in vitro and auditory cued fear conditioning in vivo induce nucleus-scale restructuring of chromatin within minutes.

In vivo modeling of human neuron dynamics and Down syndrome.

Harnessing the potential of human stem cells for modeling the physiology and diseases of cortical circuitry requires monitoring cellular dynamics in vivo. We show that human induced pluripotent stem cell (iPSC)-derived cortical neurons transplanted into the adult mouse cortex consistently organized into large (up to ~100 mm) vascularized neuron-glia territories with complex cytoarchitecture. Longitudinal imaging of >4000 grafted developing human neurons revealed that neuronal arbors refined via branch-specific retraction; human synaptic networks substantially restructured over 4 months, with balanced rates of synapse formation and elimination; and oscillatory population activity mirrored the patterns of fetal neural networks.

Filopodyan: An open-source pipeline for the analysis of filopodia.

Filopodia have important sensory and mechanical roles in motile cells. The recruitment of actin regulators, such as ENA/VASP proteins, to sites of protrusion underlies diverse molecular mechanisms of filopodia formation and extension. We developed Filopodyan (filopodia dynamics analysis) in Fiji and R to measure fluorescence in filopodia and at their tips and bases concurrently with their morphological and dynamic properties.

Directional Emission from Dielectric Leaky-Wave Nanoantennas.

An important source of innovation in nanophotonics is the idea to scale down known radio wave technologies to the optical regime. One thoroughly investigated example of this approach are metallic nanoantennas which employ plasmonic resonances to couple localized emitters to selected far-field modes. While metals can be treated as perfect conductors in the microwave regime, their response becomes Drude-like at optical frequencies.

Reflective Metasurfaces for Incoherent Light To Bring Computer Graphics Tricks to Optical Systems.

The normal mapping technique is widely used in computer graphics to visualize three-dimensional (3D) objects displayed on a flat screen. Taking advantage of optical properties of metasurfaces, which provide a highly efficient approach for manipulation of incident light wavefront, we have designed a metasurface to implement diffuse reflection and used the concept of normal mapping to control its scattering properties. As a proof of principle, we have fabricated and characterized a flat diffuse metasurface imitating lighting and shading effects of a 3D cube.

Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro.

A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo.

Dynamics of dendritic spines in the mouse auditory cortex during memory formation and memory recall.

Long-lasting changes in synaptic connections induced by relevant experiences are believed to represent the physical correlate of memories. Here, we combined chronic in vivo two-photon imaging of dendritic spines with auditory-cued classical conditioning to test if the formation of a fear memory is associated with structural changes of synapses in the mouse auditory cortex. We find that paired conditioning and unpaired conditioning induce a transient increase in spine formation or spine elimination, respectively.

The swindon foot and ankle questionnaire: is a picture worth a thousand words?

Objectives. Despite increased awareness of the high prevalence and significance of foot and ankle problems in rheumatoid arthritis (RA), feet remain neglected. Reasons may include the perception that feet are difficult to assess, they are not included in the DAS28, and lack of freely available foot screening tools specific for RA.