Cell death is prevalent throughout life; however, the coordinated interactions and roles of phagocytes during corpse removal in the live brain are poorly understood. We developed photochemical and viral methodologies to induce death in single cells and combined this with intravital optical imaging. This approach allowed us to track multicellular phagocytic interactions with precise spatiotemporal resolution. Astrocytes and microglia engaged with dying neurons in an orchestrated and synchronized fashion. Each glial cell played specialized roles: Astrocyte processes rapidly polarized and engulfed numerous small dendritic apoptotic bodies, while microglia migrated and engulfed the soma and apical dendrites. The relative involvement and phagocytic specialization of each glial cell was plastic and controlled by the receptor tyrosine kinase Mertk. In aging, there was a marked delay in apoptotic cell removal. Thus, a precisely orchestrated response and cross-talk between glial cells during corpse removal may be critical for maintaining brain homeostasis.

Methods that combine lineage tracing with cellular transgenesis are needed in order to determine mechanisms that specify neural cell types. Currently available methods include viral infection and Cre-mediated recombination. In utero electroporation (IUE) has been used in multiple species to deliver multiple transgenes simultaneously into neural progenitors. In standard IUE, most plasmids remain episomal, are lost during cell division, and so transgenes are not expressed in the complete neural lineage. Here we combine IUE with a binary piggyBac transposon system (PB-IUE), and show that unlike conventional IUE, a single embryonic transfection of neocortical radial glia with a piggyBac transposon system results in stable transgene expression in the neural lineage of radial glia: cortical neurons, astrocytes, oligodendrocytes, and olfactory bulb interneurons. We also developed a modular toolkit of donor and helper plasmids with different promoters that allows for shRNA, bicistronic expression, and trangenesis in subsets of progenitors. As a demonstration of the utility of the toolkit we show that transgenesis of epidermal growth factor receptor (EGFR) expands the number of astrocytes and oligodendrocyrtes generated from progenitors. The relative ease of implementation and experimental flexibility should make the piggyBac IUE method a valuable new tool for tracking and manipulating neural lineages.

Lineage progression and diversification is regulated by the coordinated action of unique sets of transcription factors. Oligodendrocytes (OL) and astrocytes (AS) comprise the glial sub-lineages in the central nervous system (CNS) and how their associated regulatory factors orchestrate lineage diversification during development and disease remains an open question. Sox10 and NFIA are key transcriptional regulators of gliogenesis associated with OL and AS. We found that NFIA inhibits Sox10 induction of OL differentiation through direct association and antagonism of its function. Conversely, we found that Sox10 antagonizes NFIA function and suppresses AS differentiation. Using this developmental paradigm as a model for glioma, we found that this relationship similarly regulates the generation of glioma sub-types. These studies describe the antagonistic relationship between Sox10/NFIA that regulates the balance of OL and AS fate during development and demonstrate for the first time that the transcriptional processes governing glial sub-lineage diversification oversee the generation of glioma sub-types.

Li-CO 2 batteries have attracted ever increasing attention due to their high energy and power densities. However, Li 2 CO 3 formed during the discharge process is difficult to decompose, leading to a large charge overpotential and poor cyclability. Thus, high-performance and low-cost catalysts that can be integrated into the electrode architecture are urgently needed for the development of practical Li-CO 2 batteries with a low overpotential and long cyclability. Herein, a high-performance composite catalyst is reported based on carbon quantum dots supported by holey graphene (CQD/hG), which, when used as the cathodic catalyst in a Li-CO 2 battery, can support the fast formation and decomposition of Li 2 CO 3 in organic electrolytes and achieve an overpotential as low as 1.02 V (Li/Li + ) at current density of 0.1 A g −1 . The discharge capacity of this Li-CO 2 battery is 12300 mAh g −1 under the current density of 0.5 A g −1 , showing an excellent long-term stability with up to 235 cycles even at a high current density of 1 A g −1 . The observed superb battery performance is attributable to synergistic effects that the CQD/hG composite architecture provides a high catalytic activity of the defect-rich CQDs and fast electron/electrolyte transport through the conducting holey graphene sheets.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adfm.201804630. now facing. [1] Therefore, it is more important now than ever to develop renewable and clean energy technologies. [2] Although Li-ion batteries have been successfully commercialized as the clean energy source for consumer electronic devices, the low energy density of the stateof-the-art Li-ion batteries with the intrinsic Li + intercalation mechanism limited their use for energy-demanding applications, including electrical vehicles automobiles for long-distance transportation. [3] To address this issue, metal-air batteries with much higher energy and power densities than those of Li-ion batteries have attracted more and more interests. [4] For example, the Li/Na-O 2 batteries have been extensively studied and recently demonstrated with high energy densities and a long cycle life. [5] As a particular type of metalair batteries, Li-CO 2 batteries based on the redox reaction between the Li anode and CO 2 cathode (4Li + 3CO 2 = 2Li 2 CO 3 + C) [1b,6] can deliver ten times more energy density than that of a Li-ion battery. Furthermore, Li-CO 2 battery research is significant for the exploration missions on Mars, where CO 2 gas constitutes 96% of the atmosphere.A rechargeable Li-CO 2 battery using Ketjen Black (KB) as a cathodic catalyst was first reported in 2014, [7] which was cycled only for seven times with a limited discharge capacity of 1000 mAh g −1 due to a poor catalytic activity of the KB catalyst. This is because the main discharge product, Li 2 CO 3 , is a wide bandgap insulator with a sluggish kinetics for electrochemical decomposition during the charge process, leading to a high charge po...

ArcLight, a genetically encoded fluorescent protein voltage probe with a large ΔF/ΔV, is a fusion between the voltage sensing domain of the Ciona instestinalis voltage sensitive phosphatase and super ecliptic pHluorin carrying a single mutation (A227D in the fluorescent protein). Without this mutation the probe produces only a very small change in fluorescence in response to voltage deflections (∼1%). The large signal afforded by this mutation allows optical detection of action potentials and sub-threshold electrical events in single-trials in vitro and in vivo. However, it is unclear how this single mutation produces a probe with such a large modulation of its fluorescence output with changes in membrane potential. In this study, we identified which residues in super ecliptic pHluorin (vs eGFP) are critical for the ArcLight response, as a similarly constructed probe based on eGFP also exhibits large response amplitude if it carries these critical residues. We found that D147 is responsible for determining the pH sensitivity of the fluorescent protein used in these probes but by itself does not result in a voltage probe with a large signal. We also provide evidence that the voltage dependent signal of ArcLight is not simply sensing environmental pH changes. A two-photon polarization microscopy study showed that ArcLight's response to changes in membrane potential includes a reorientation of the super ecliptic pHluorin. We also explored different changes including modification of linker length, deletion of non-essential amino acids in the super ecliptic pHluorin, adding a farnesylation site, using tandem fluorescent proteins and other pH sensitive fluorescent proteins.

Our research supported use of the ECDC algorithm, in which syphilis screening begins with a treponemal immunoassay that is followed by a second, different treponemal assay as a confirmatory test in high-prevalence populations. In addition, our results indicated that nontreponemal assay is unnecessary for syphilis diagnosis but can be recommended for determining serological activity and the effect of syphilis treatment.

Silver nanoalloy electrocatalysts with comparable activity and better stability than commercial Pt/C for oxygen reduction reaction (ORR) in advanced metal–air batteries and fuel cells.

Alloy nanoclusters (“nanoalloys”) are of interest because of their novel properties compared to bulk alloys. In this paper, the thermal behavior, including melting, of 55 atom Ag−Au nanoalloys has been investigated by molecular dynamics simulations using the Gupta many-body potential. Single melting runs exhibit a sharp transition from the cluster ground structures to the melt, while averaged results indicate that melting occurs in a size- and composition-dependent temperature range. The transition point (melting point) decreases with increasing Au concentration. Gold-rich Au n Ag55 - n nanoalloys with n = 30−55 exhibit a very smooth transition from the ground state to their undercooled melt. Their thermal stability is influenced by the glass transition behavior of the pure amorphous Au55 cluster.