Neuromodulation of Brain States Lee, Seung-Hee; Dan, Yang
Neuron (Cambridge, Mass.),
10/2012, Letnik:
76, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Switches between different behavioral states of the animal are associated with prominent changes in global brain activity, between sleep and wakefulness or from inattentive to vigilant states. What ...mechanisms control brain states, and what are the functions of the different states? Here we summarize current understanding of the key neural circuits involved in regulating brain states, with a particular emphasis on the subcortical neuromodulatory systems. At the functional level, arousal and attention can greatly enhance sensory processing, whereas sleep and quiet wakefulness may facilitate learning and memory. Several new techniques developed over the past decade promise great advances in our understanding of the neural control and function of different brain states.
What mechanisms control brain states such as sleep and wakefulness, and what are the functions of the different states? Here Lee and Dan summarize current understanding of the key neural circuits involved in regulating brain states, with a particular emphasis on the subcortical neuromodulatory systems.
High peak-to-average power ratio of the transmit signal is a major drawback of multicarrier transmission such as OFDM or DMT. This article describes some of the important PAPR reduction techniques ...for multicarrier transmission including amplitude clipping and filtering, coding, partial transmit sequence, selected mapping, interleaving, tone reservation, tone injection, and active constellation extension. Also, we make some remarks on the criteria for PAPR reduction technique selection and briefly address the problem of PAPR reduction in OFDMA and MIMO-OFDM.
Glutamine is an essential nutrient that regulates energy production, redox homeostasis, and signaling in cancer cells. Despite the importance of glutamine in mitochondrial metabolism, the ...mitochondrial glutamine transporter has long been unknown. Here, we show that the SLC1A5 variant plays a critical role in cancer metabolic reprogramming by transporting glutamine into mitochondria. The SLC1A5 variant has an N-terminal targeting signal for mitochondrial localization. Hypoxia-induced gene expression of the SLC1A5 variant is mediated by HIF-2α. Overexpression of the SLC1A5 variant mediates glutamine-induced ATP production and glutathione synthesis and confers gemcitabine resistance to pancreatic cancer cells. SLC1A5 variant knockdown and overexpression alter cancer cell and tumor growth, supporting an oncogenic role. This work demonstrates that the SLC1A5 variant is a mitochondrial glutamine transporter for cancer metabolic reprogramming.
Display omitted
•The SLC1A5 variant is a mitochondrial glutamine transporter•The SLC1A5 variant has a mitochondrial targeting sequence•Hypoxia controls SLC1A5 variant expression through HIF-2α•The SLC1A5 variant mediates mitochondrial glutamine metabolism in cancer
Despite the importance of glutamine in cancer metabolism, the mitochondrial glutamine transporter has long been unknown. Yoo et al. show that a variant of SLC1A5 has a mitochondrial targeting signal for mitochondrial localization and is induced by HIF-2α. SLC1A5 variant knockdown suppressed cancer cell growth, supporting an oncogenic role.
Disodium terephthalate and its various derivatives are synthesized via simple acid‐base chemistry for anode materials in Na ion batteries. They show excellent electrochemical performance, including ...little capacity fading over 90 cycles, ideal redox potential, and excellent rate performance, making them promising candidates for Na ion batteries.
Designing chiral channels in organic frameworks presents an ongoing challenge due to the intricate control of size, shape, and functionality required. A novel approach is presented, which crafts ...enantiomeric chiral channels in metal‐peptide networks (MPNs) by integrating short foldamer ligands with CuI clusters. The MPN structure serves as a 3D blueprint for host‐guest chemistry, fostering modular substitution to refine chiral channel properties at the atomic scale. Incorporating hydrogen bond networks augments guest molecule interactions with the channel surface. This approach expedites enantiomer discrimination in racemic mixtures and incites adaptable guest molecules to take on specific axially chiral conformations. Distinct from traditional metal‐organic frameworks (MOFs) and conventional reticular architectures, this foldamer‐based methodology provides a predictable and customizable host‐guest interaction system within a 3D topology. This innovation sets the stage for multifunctional materials that merge host‐guest interaction systems with metal‐complex properties, opening up potential applications in catalysis, sensing, and drug delivery.
This groundbreaking research uncovers an approach for crafting chiral channels in metal‐peptide networks (MPNs). The strategic integration of foldamer ligands and CuI clusters allows precise, atomic‐level modifications. The technique expedites enantiomer discrimination in mixtures and prompts adaptable molecules to adopt specific chiral forms. It promises the potential for multifunctional materials useful in catalysis, drug delivery, and sensing technologies.
Glia contribute to synapse elimination through phagocytosis in the central nervous system. Despite the important roles of this process in development and neurological disorders, the identity and ...regulation of the "eat‐me" signal that initiates glia‐mediated phagocytosis of synapses has remained incompletely understood. Here, we generated conditional knockout mice with neuronal‐specific deletion of the flippase chaperone Cdc50a, to induce stable exposure of phosphatidylserine, a well‐known "eat‐me" signal for apoptotic cells, on the neuronal outer membrane. Surprisingly, acute Cdc50a deletion in mature neurons causes preferential phosphatidylserine exposure in neuronal somas and specific loss of inhibitory post‐synapses without effects on other synapses, resulting in abnormal excitability and seizures. Ablation of microglia or the deletion of microglial phagocytic receptor Mertk prevents the loss of inhibitory post‐synapses and the seizure phenotype, indicating that microglial phagocytosis is responsible for inhibitory post‐synapse elimination. Moreover, we found that phosphatidylserine is used for microglia‐mediated pruning of inhibitory post‐synapses in normal brains, suggesting that phosphatidylserine serves as a general "eat‐me" signal for inhibitory post‐synapse elimination.
SYNOPSIS
Neuronal‐specific deletion of the flippase chaperone Cdc50a leads to exposure of phosphatidylserin on neuronal outer membranes causing specific loss of inhibitory post‐synapses and seizures. Microglial phagocytosis via the phagocytic receptor MERTK promotes inhibitory post‐synapse elimination in Cdc50a cKO brains. Inhibitory post‐synapses in normal juvenile brains also use phosphatidylserine for synapse elimination, suggesting that phosphatidylserine exposure functions as an “eat‐me” signal for microglia‐dependent inhibitory post‐synapse elimination.
Neuronal Cdc50a deletion induces rapid lethality with appearance of audiogenic seizure.
Neuronal Cdc50a deletion causes the specific loss of inhibitory post‐synapses without affecting other synapses.
Ablating microglia or deleting microglial Mertk rescues the loss of inhibitory post‐synapses and seizure behaviors in Cdc50a cKO mice.
Microglial Mertk deletion increases the number of phosphatidylserine‐exposed inhibitory post‐synapses in the wild‐type juvenile brains.
Mouse models with increased neuron‐specific exposure of an apoptotic cell‐defining phospholipid provide insight into the nature of the "eat‐me" signal and its recognition during synapse elimination.
Common medications for treating inflammatory bowel disease (IBD) have limited therapeutic efficacy and severe adverse effects. This underscores the urgent need for novel therapeutic approaches that ...can effectively target inflamed sites in the gastrointestinal tract upon oral administration, exerting potent therapeutic efficacy while minimizing systemic effects. Here, we report the construction and in vivo therapeutic evaluation of a library of anti‐inflammatory glycocalyx‐mimicking nanoparticles (designated GlyNPs) in a mouse model of IBD. The anti‐inflammatory GlyNP library was created by attaching bilirubin (BR) to a library of glycopolymers composed of random combinations of the five most naturally abundant sugars. Direct in vivo screening of 31 BR‐attached anti‐inflammatory GlyNPs via oral administration into mice with acute colitis led to identification of a candidate GlyNP capable of targeting macrophages in the inflamed colon and effectively alleviating colitis symptoms. These findings suggest that the BR‐attached GlyNP library can be used as a platform to identify anti‐inflammatory nanomedicines for various inflammatory diseases.
A library of bilirubin‐attached glycocalyx‐mimicking nanoparticles was constructed as a platform enabling identification of an anti‐inflammatory nanomedicine. Direct in vivo screening of the nanoparticle library by oral administration into mice with acute colitis led to identification of a candidate anti‐inflammatory nanomedicine capable of targeting macrophages in the inflamed colon and effectively alleviating colitis symptoms.
PDF
