Studies in rodent epilepsy models suggest that GABAergic interneuron progenitor grafts can reduce hyperexcitability and seizures in temporal lobe epilepsy (TLE). Although integration of the transplanted cells has been proposed as the underlying mechanism for these disease-modifying effects, prior studies have not explicitly examined cell types and synaptic mechanisms for long-term seizure suppression. To address this gap, we transplanted medial ganglionic eminence (MGE) cells from embryonic day 13.5 VGAT-Venus or VGATChR2-EYFP transgenic embryos into the dentate gyrus (DG) of adult mice 2 weeks after induction of TLE with pilocarpine. Beginning 3-4 weeks after status epilepticus, we conducted continuous video-electroencephalographic recording until 90 -100 d. TLE mice with bilateral MGE cell grafts in the DG had significantly fewer and milder electrographic seizures, compared with TLE controls. Immunohistochemical studies showed that the transplants contained multiple neuropeptide or calcium-binding protein-expressing interneuron types and these cells established dense terminal arborizations onto the somas, apical dendrites, and axon initial segments of dentate granule cells (GCs). A majority of the synaptic terminals formed by the transplanted cells were apposed to large postsynaptic clusters of gephyrin, indicative of mature inhibitory synaptic complexes. Functionality of these new inhibitory synapses was demonstrated by optogenetically activating VGAT-ChR2-EYFP-expressing transplanted neurons, which generated robust hyperpolarizations in GCs. These findings suggest that fetal GABAergic interneuron grafts may suppress pharmacoresistant seizures by enhancing synaptic inhibition in DG neural circuits.
Arthroscopic optical coherence tomography may be clinically useful for early detection of articular cartilage injury and nondestructive assessment of articular cartilage repair.
The physical and chemical properties of microplastics and their environmental distributions may provide clues about their sources and inform their fate. We demonstrate the value of extensive monitoring of microplastics in an urban bay, San Francisco Bay. Surface water, fish, sediment, stormwater runoff, and treated wastewater were sampled across the bay and adjacent national marine sanctuaries (NMS). We found microplastics and other anthropogenic microdebris ("microdebris") in all sample types. Concentrations were higher in the bay than in the NMS, and within the bay, concentrations were higher during the wet season than during the dry season. The fate of microdebris varied depending on their morphologies and densities: fibers were dominant in fish, black rubbery fragments were common in sediment, as were fibers, while buoyant fragments and fibers were widely observed in surface waters. Notably, we found large amounts of black rubbery fragments, an emerging contaminant, in stormwater. Moreover, stormwater was a significant pathway of microdebris, with concentrations roughly 140 times greater than those found in wastewater, which was dominated by fibers. Overall, we demonstrate the value of multimatrix regional monitoring to evaluate the sources and fate of microplastics, which can inform effective mitigation for other urban bays around the world.
The effects of bioturbation on the performance of attenuation by sediment deposition and activated carbon to reduce risks from DDT-contaminated sediment were assessed for DDT sediment-water flux, biouptake, and passive sampler (PE) uptake in microcosm experiments with a freshwater worm, Lumbriculus variegatus. A thin-layer of clean sediment (0.5 cm) did not reduce the DDT flux when bioturbation was present, while a thin (0.3 cm) AC cap was still capable of reducing the DDT flux by 94%. Bioturbation promoted AC sequestration by reducing the 28-day DDT biouptake (66%) and DDT uptake into PE (>99%) compared to controls. Bioturbation further promoted AC-sediment contact by mixing AC particles into underlying sediment layers, reducing PE uptake (55%) in sediment compared to the AC cap without bioturbation. To account for the observed effects from bioturbation, a mass transfer model together with a biodynamic model were developed to simulate DDT flux and biouptake, respectively, and models confirmed experimental results. Both experimental measurements and modeling predictions imply that thin-layer activated carbon placement on sediment is effective in reducing the risks from contaminated sediments in the presence of bioturbation, while natural attenuation process by clean sediment deposition may be delayed by bioturbation.
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