14 research outputs found

    System Design and Locomotion of Superball, an Untethered Tensegrity Robot

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    The Spherical Underactuated Planetary Exploration Robot ball (SUPERball) is an ongoing project within NASA Ames Research Center's Intelligent Robotics Group and the Dynamic Tensegrity Robotics Lab (DTRL). The current SUPERball is the first full prototype of this tensegrity robot platform, eventually destined for space exploration missions. This work, building on prior published discussions of individual components, presents the fully-constructed robot. Various design improvements are discussed, as well as testing results of the sensors and actuators that illustrate system performance. Basic low-level motor position controls are implemented and validated against sensor data, which show SUPERball to be uniquely suited for highly dynamic state trajectory tracking. Finally, SUPERball is shown in a simple example of locomotion. This implementation of a basic motion primitive shows SUPERball in untethered control

    Right Isomerism of the Brain in Inversus Viscerum Mutant Mice

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    Left-right (L-R) asymmetry is a fundamental feature of higher-order neural function. However, the molecular basis of brain asymmetry remains unclear. We recently reported L-R asymmetry of hippocampal circuitry caused by differential allocation of N-methyl-D-aspartate receptor (NMDAR) subunit GluRε2 (NR2B) in hippocampal synapses. Using electrophysiology and immunocytochemistry, here we analyzed the hippocampal circuitry of the inversus viscerum (iv) mouse that has a randomized laterality of internal organs. The iv mouse hippocampus lacks L-R asymmetry, it exhibits right isomerism in the synaptic distribution of the ε2 subunit, irrespective of the laterality of visceral organs. This independent right isomerism of the hippocampus is the first evidence that a distinct mechanism downstream of the iv mutation generates brain asymmetry

    Palmitoylation of the pore-forming subunit of Ca(v)1.2 controls channel voltage sensitivity and calcium transients in cardiac myocytes

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    Mammalian voltage-activated L-type Ca2+ channels, such as Ca(v)1.2, control transmem- brane Ca2+ fluxes in numerous excitable tissues. Here, we report that the pore-forming α1C subunit of Ca(v)1.2 is reversibly palmitoylated in rat, rabbit, and human ventricular myocytes. We map the palmitoylation sites to two regions of the channel: The N termi- nus and the linker between domains I and II. Whole-cell voltage clamping revealed a rightward shift of the Ca(v)1.2 current–voltage relationship when α1C was not palmi- toylated. To examine function, we expressed dihydropyridine-resistant α1C in human induced pluripotent stem cell-derived cardiomyocytes and measured Ca2+ transients in the presence of nifedipine to block the endogenous channels. The transients generated by unpalmitoylatable channels displayed a similar activation time course but signifi- cantly reduced amplitude compared to those generated by wild-type channels. We thus conclude that palmitoylation controls the voltage sensitivity of Ca(v)1.2. Given that the identified Ca(v)1.2 palmitoylation sites are also conserved in most Ca(v)1 isoforms, we propose that palmitoylation of the pore-forming α1C subunit provides a means to regulate the voltage sensitivity of voltage-activated Ca 2+ channels in excitable cells

    The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

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    INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

    L-R laterality defects in the hippocampal circuitry of <i>iv/iv</i> mice.

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    <p>(A) A schematic representation of synaptic inputs onto the basal and apical dendrites of CA1 pyramidal cells and the positioning of electrodes. In slices from naive and VHCT mice, electrical stimulation was applied at the <i>stratum oriens</i> [Stim.(SO)] or <i>stratum radiatum</i> [Stim.(SR)] of area CA1. Whole-cell recordings [Rec.(WC)] were made from CA1 pyramidal cells. Basal and Apical represent recordings from basal and apical synapses, respectively. Sch, schaffer collateral fibers; Com, commissural fibers. (B to F) Inhibitory effects of Ro 25-6981 on NMDA EPSCs from CA1 pyramidal neurons. Sample superimposed traces indicate NMDA EPSCs recorded in the absence (Control) and presence of Ro 25-6981 (Ro, 0.6 µM). The levels of inhibition were maximal after exposure to Ro 25-6981 for 50 to 60 min. Left and Right indicate recordings from left and right hippocampal slices, respectively. Each trace is the average of five consecutive recordings. Scale bars, 25 pA (vertical) and 100 ms (horizontal). Relative amplitudes of NMDA EPSCs in the presence of Ro 25-6981 are expressed as percentages of control responses. Error bars represent s.e.m. (<i>n = </i>7 each, *<i>P</i><0.01, absence of an asterisk indicates <i>P</i>>0.05).</p

    Right isomerism of the <i>iv</i>/<i>iv</i> mouse hippocampus.

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    <p>Left and right CA3 pyramidal neurons and their axons are colored red and blue, respectively. A postsynaptic CA1 pyramidal neuron is at the center, colored black, and it represents postsynaptic neurons in both left and right hemispheres. Closed and open circles are ε2-dominant and ε2-nondominant synapses, respectively. Apical, apical dendrites; Basal, basal dendrites.</p

    Developmental asymmetry of LTP at hippocampal CA1 synapses.

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    <p>Schematic diagrams of the arrangement of electrodes for extracellular recording. To activate basal (Basal) or apical dendritic synapses (Apical), a stimulating electrode was placed at the <i>stratum oriens</i> [Stim.(SO)] or <i>stratum radiatum</i> [Stim.(SR)] of area CA1, respectively. fEPSPs were recorded with an extracellular electrode [Rec.(field)]. LTP was induced with tetanic stimulation at time 0 (arrow). Open and filled symbols represent 7- to 9-week-old mice and postnatal 9- to11-day-old mice, respectively. Square and circle symbols indicate recordings from basal and apical dendritic synapses, respectively. Error bars represent s.e.m. (<i>n = </i>7 to 9).</p

    Palmitoylation of the pore-forming subunit of Ca(v)1.2 controls channel voltage sensitivity and calcium transients in cardiac myocytes

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    This data set contains data used to form the basis of a scientific publication. Microsoft Excel files contain: • Quantitative data from analysis of images of western immunoblots • Quantitative data from analysis of electrophysiological recordings of current records • Quantitative data from analysis of intracellular calcium concentrations in cardiac myocytes • Quantitative modelling of action potentials and calcium transients Microsoft Powerpoint files contain original uncropped images of western immunoblots Python code for a model of cardiac calcium handling and electrophysiology, implemented in the myokit ide
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