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“Inflammatory” Cytokines   总被引:4,自引:0,他引:4  
If cytokines are constitutively expressed by and act on neurons in normal adult brain, then we may have to modify our current view that they are predominantly inflammatory mediators. We critically reviewed the literature to determine whether we could find experimental basis for such a modification. We focused on two "proinflammatory" cytokines, interleukin (IL)-1 and tumor necrosis factor-alpha (TNFalpha) because they have been most thoroughly investigated in shaping our current thinking. Evidence, although equivocal, indicates that the genes coding for these cytokines and their accessory proteins are expressed by neurons, in addition to glial cells, in normal brain. Their expression is region- and cell type-specific. Furthermore, bioactive cytokines have been extracted from various regions of normal brain. The cytokines' receptors selectively are present on all neural cell types, rendering them responsive to cytokine signaling. Blocking their action modifies multiple neural "housekeeping" functions. For example, blocking IL-1 or TNFalpha by several independent means alters regulation of sleep. This indicates that these cytokines likely modulate in the brain behavior of a normal organism. In addition, these cytokines are likely involved in synaptic plasticity, neural transmission, and Ca2+ signaling. Thus, the evidence strongly suggests that these cytokines perform neural functions in normal brain. We therefore propose that they should be thought of as neuromodulators in addition to inflammatory mediators.  相似文献   

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There is an intensive search for heterogeneous single atom catalysts (SACs) of high activity, efficiency, durability, and selectivity for a wide variety of electrocatalytic conversion and chemical reactions, such as the hydrogen evolution reaction (HER), oxygen evolution/reduction reaction (OER and ORR), CO2 reduction reaction (CO2 RR), and nitrogen reduction reaction (NRR). With the downsizing from nanoparticles and clusters to single atoms, there are steady changes in the bond and coordination environment for each and every atom involved. Indeed, the single atoms in these electrocatalysts are not “singles”; they are “married” to the supporting surfaces, and their performance is controlled by the bonding and coordination with the substrate surfaces. Herein, an overview is presented on the brief history leading to the rapid development of SACs and their current status, by focusing on their synthesis, control of composition, strategies to realize single atoms with the desired bonds and coordination, and targeted performance in selected reactions. Their applications in the selected spectrum of energy conversion and chemical reactions are discussed, in relation to their structures at varying length scales down to the atomic level. A particular emphasis is placed on on‐going research activities, together with the future perspectives and particular challenges for SACs.  相似文献   

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The United Nations (UN) Convention on the Rights of Persons with Disabilities (CRPD) is the most up‐to‐date international legal instrument concerning the rights of persons with disabilities. Such persons are taken to include those with serious mental disorders. According to an authoritative interpretation of a crucial Article (Article 12 ‐ Equal recognition before the law) by the UN CRPD Committee, involuntary detention and treatment of people with mental health disabilities are prohibited under the Convention. Both conventional mental health law and “capacity‐based” law are deemed to violate the Convention. However, some other UN bodies are not in full agreement (for example, the UN Human Rights Committee and the Subcommittee on Prevention of Torture and Other Cruel, Inhuman or Degrading Treatment or Punishment), while others are less explicitly absolutist (for example, the Human Rights Council). Furthermore, strong criticisms of the position of the CRPD Committee have been mounted from a number of academic quarters. These criticisms center on whether the role of a person's ability to make a decision can be ignored, no matter the circumstances. Much of the above debate turns on the concept of “legal capacity” and the now often‐repeated precept that one must always respect the “will and preferences” of the person with a disability. However, “will and preferences” remains undefined. In this paper, I offer an analysis of “will and preferences” that can clarify interventions that may be acceptable or non‐acceptable under the terms of the UN Convention.  相似文献   

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