PURPOSE To develop and characterize a mouse model of spontaneous recurrent seizures following nerve agent-induced status epilepticus (SE) and test the efficacy of existing antiepileptic drugs. METHODS SE was induced in telemeterized male C57Bl6/J **** by soman exposure, and electroencephalographic activity was recorded for 4-6 weeks. **** were treated with antiepileptic drugs (levetiracetam, valproic acid, phenobarbital) or corresponding vehicles for 14 d after exposure, followed by 14 d of drug washout. Survival, body weight, seizure characteristics, and histopathology were used to characterize the acute and chronic effects of nerve agent exposure and to evaluate the efficacy of treatments in mitigating or preventing neurological effects. RESULTS Spontaneous recurrent seizures manifested in all survivors, but the number and frequency of seizures varied considerably among ****. In untreated ****, seizures became longer over time. Moderate to severe histopathology was observed in the amygdala, piriform cortex, and CA1. Levetiracetam provided modest improvements in neurological parameters such as reduced spike rate and improved histopathology scores, whereas valproic acid and phenobarbital were largely ineffective. CONCLUSIONS This model of post-SE spontaneous recurrent seizures differs from other experimental models in the brief latency to seizure development, the occurrence of seizures in 100 % of exposed animals, and the lack of damage to CA4/dentate gyrus. It may serve as a useful tool for rapidly and efficiently screening novel therapies that would be effective against severe epilepsy cases. Published by Elsevier B.V.In this research, a novel ultrasound-assisted extraction (USAE) method using a one-phase solvent (isopropanol, IPA) combined with liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QToF-MS) was developed for exhaustive profiling of egg yolk lipids, which are considered to be essential nutrients that have important functions for human health. Compared with IPA-vortex extraction method, the optimized IPA-USAE method shows better performance in terms of extraction time, lipid losses, lipid recoveries and the number of lipids identified. https://www.selleckchem.com/products/pyr-41.html With this established simple, high throughput and reliable analytical approach, untargeted comprehensive lipid profiling of four kinds of egg yolks was achieved, thus providing a powerful tool for nutritional research of egg lipids. Considering that the lipids contained in egg yolk are quite abundant in both quantity and species, the proposed IPA-USAE combined with LC-ESI-QToF-MS is also potentially applicable to comprehensive extraction and profiling of lipids in other biological samples. Collagens are large structural proteins that are prevalent in mammalian connective tissue. Peptides designed to include a glycine-proline-hydroxyproline (GPO) amino acid triad are biomimetic analogs of the collagen triple helix, a fold that is a hallmark of collagen-like sequences. To inform the rational engineering of collagen-like peptides and proteins for food systems, we report the crystal structure of the (GPO)10 peptide at 0.89-Å resolution, solved using direct methods. We determined that a single chain in the asymmetric unit forms a pseudo-hexagonal network of triple helices that have a pitch variation consistent with the model 7/2 helix (3.5 residues per turn). The proline rings occupied one of two states, while the helix was found to have a well-defined hydration shell involved in the stabilization of the inter-helix crystal network. This structure offers a new high-resolution basis for understanding the hierarchical assembly of native collagens, which will aid the food industry in engineering new sustainable food systems. In recent years, aberration correction has slowly become standard in high-end conventional transmission electron microscopy (50-200 kV). However, the integration of correctors to low voltage transmission systems (5-25 kV) has proved to be difficult. The hexapole corrector based on permanent magnet technology seems to be a promising solution for the correction of the primary spherical aberration. Especially if the compact dimensions and low complexity are to be preserved. However, the high importance of chromatic aberration with respect to the microscope resolution still remains a serious obstacle. It must be taken into account when the design is made. The following presented concept is intended exclusively for STEM mode to avoid additional chromatic deterioration caused by electron passage through the sample. The design of the key segment (transfer lens doublet) is discussed in detail, including its compensation systems, which guarantees proper alignment. Gravity-driven membrane (GDM) filtration system is a promising process for decentralized drinking water treatment. During the operation, membrane relaxation and shear stress could be simply achieved by intermittent filtration and water disturbance (created by occasionally shaking membrane model or stirring water in membrane tank), respectively. To better understand the impact of membrane relaxation and shear stress on the biofouling layer and stable flux in GDM system, action of daily 60-min intermission, daily flushing (cross-flow velocity = 10 cm s-1, 1 min), and the combination of the two (flushed right after the 60-min intermission) were compared. The results showed that membrane relaxation and shear stress lonely was ineffective in improving the stable flux, while their combination enhanced the stable flux by 70%. A more open and spatially heterogeneous biofouling layer with a low extracellular polymeric substance (EPS) content and a high microbial activity was formed under the combination of membrane relaxation and shear stress. In-situ optical coherence tomography (OCT) observation revealed that, during intermission, the absence of pushing force by water flow induced a reversible expansion of biofouling layer, and the biofouling layer restored to its initial state soon after resuming filtration. Shear stress caused abrasion and erosion on the biofouling surface, but it exerted little effect on the interior of biofouling layer. Under the combination, however, both the surface and interior of biofouling layer were disturbed because of 1) the water vortexes caused by rough biofouling layer surface, and 2) the porous structure after 60-min intermission. This disturbance, in turn, helped the biofouling layer maintain its roughness and porosity, thereby improving the stable flux of GDM system.
PURPOSE To develop and characterize a mouse model of spontaneous recurrent seizures following nerve agent-induced status epilepticus (SE) and test the efficacy of existing antiepileptic drugs. METHODS SE was induced in telemeterized male C57Bl6/J mice by soman exposure, and electroencephalographic activity was recorded for 4-6 weeks. Mice were treated with antiepileptic drugs (levetiracetam, valproic acid, phenobarbital) or corresponding vehicles for 14 d after exposure, followed by 14 d of drug washout. Survival, body weight, seizure characteristics, and histopathology were used to characterize the acute and chronic effects of nerve agent exposure and to evaluate the efficacy of treatments in mitigating or preventing neurological effects. RESULTS Spontaneous recurrent seizures manifested in all survivors, but the number and frequency of seizures varied considerably among mice. In untreated mice, seizures became longer over time. Moderate to severe histopathology was observed in the amygdala, piriform cortex, and CA1. Levetiracetam provided modest improvements in neurological parameters such as reduced spike rate and improved histopathology scores, whereas valproic acid and phenobarbital were largely ineffective. CONCLUSIONS This model of post-SE spontaneous recurrent seizures differs from other experimental models in the brief latency to seizure development, the occurrence of seizures in 100 % of exposed animals, and the lack of damage to CA4/dentate gyrus. It may serve as a useful tool for rapidly and efficiently screening novel therapies that would be effective against severe epilepsy cases. Published by Elsevier B.V.In this research, a novel ultrasound-assisted extraction (USAE) method using a one-phase solvent (isopropanol, IPA) combined with liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QToF-MS) was developed for exhaustive profiling of egg yolk lipids, which are considered to be essential nutrients that have important functions for human health. Compared with IPA-vortex extraction method, the optimized IPA-USAE method shows better performance in terms of extraction time, lipid losses, lipid recoveries and the number of lipids identified. https://www.selleckchem.com/products/pyr-41.html With this established simple, high throughput and reliable analytical approach, untargeted comprehensive lipid profiling of four kinds of egg yolks was achieved, thus providing a powerful tool for nutritional research of egg lipids. Considering that the lipids contained in egg yolk are quite abundant in both quantity and species, the proposed IPA-USAE combined with LC-ESI-QToF-MS is also potentially applicable to comprehensive extraction and profiling of lipids in other biological samples. Collagens are large structural proteins that are prevalent in mammalian connective tissue. Peptides designed to include a glycine-proline-hydroxyproline (GPO) amino acid triad are biomimetic analogs of the collagen triple helix, a fold that is a hallmark of collagen-like sequences. To inform the rational engineering of collagen-like peptides and proteins for food systems, we report the crystal structure of the (GPO)10 peptide at 0.89-Å resolution, solved using direct methods. We determined that a single chain in the asymmetric unit forms a pseudo-hexagonal network of triple helices that have a pitch variation consistent with the model 7/2 helix (3.5 residues per turn). The proline rings occupied one of two states, while the helix was found to have a well-defined hydration shell involved in the stabilization of the inter-helix crystal network. This structure offers a new high-resolution basis for understanding the hierarchical assembly of native collagens, which will aid the food industry in engineering new sustainable food systems. In recent years, aberration correction has slowly become standard in high-end conventional transmission electron microscopy (50-200 kV). However, the integration of correctors to low voltage transmission systems (5-25 kV) has proved to be difficult. The hexapole corrector based on permanent magnet technology seems to be a promising solution for the correction of the primary spherical aberration. Especially if the compact dimensions and low complexity are to be preserved. However, the high importance of chromatic aberration with respect to the microscope resolution still remains a serious obstacle. It must be taken into account when the design is made. The following presented concept is intended exclusively for STEM mode to avoid additional chromatic deterioration caused by electron passage through the sample. The design of the key segment (transfer lens doublet) is discussed in detail, including its compensation systems, which guarantees proper alignment. Gravity-driven membrane (GDM) filtration system is a promising process for decentralized drinking water treatment. During the operation, membrane relaxation and shear stress could be simply achieved by intermittent filtration and water disturbance (created by occasionally shaking membrane model or stirring water in membrane tank), respectively. To better understand the impact of membrane relaxation and shear stress on the biofouling layer and stable flux in GDM system, action of daily 60-min intermission, daily flushing (cross-flow velocity = 10 cm s-1, 1 min), and the combination of the two (flushed right after the 60-min intermission) were compared. The results showed that membrane relaxation and shear stress lonely was ineffective in improving the stable flux, while their combination enhanced the stable flux by 70%. A more open and spatially heterogeneous biofouling layer with a low extracellular polymeric substance (EPS) content and a high microbial activity was formed under the combination of membrane relaxation and shear stress. In-situ optical coherence tomography (OCT) observation revealed that, during intermission, the absence of pushing force by water flow induced a reversible expansion of biofouling layer, and the biofouling layer restored to its initial state soon after resuming filtration. Shear stress caused abrasion and erosion on the biofouling surface, but it exerted little effect on the interior of biofouling layer. Under the combination, however, both the surface and interior of biofouling layer were disturbed because of 1) the water vortexes caused by rough biofouling layer surface, and 2) the porous structure after 60-min intermission. This disturbance, in turn, helped the biofouling layer maintain its roughness and porosity, thereby improving the stable flux of GDM system.
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