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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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One of the means of creating a more robust methodology for ecological restoration involves reducing the gap between ecological theory and restoration practices. A common strategy to do so is using meta‐analysis to understand key drivers of restoration outcomes. “Active” and “passive” is a dichotomy often used to separate restoration strategies in such meta‐analyses. We investigate previously raised concerns about selection bias and subjective categorization of strategies. We promote a paired experimental design in future empirical research and propose the use of three categories of restoration strategy in lieu of “passive” and “active” to alleviate inconsistency in definitions and categorization.  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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In this review, we focus on strategies for designing functional nano gene carriers, as well as choosing therapeutic genes targeting the tumor microenvironment. Gene mutations have a great impact on the occurrence of cancer. Thus, gene therapy plays a major role in cancer therapy and has the potential to cure cancer. Well‐designed gene therapy largely relies on effective gene carriers, which can be divided into viral carriers and non‐viral carriers. A gene carrier delivers functional genes to their intracellular target and avoids nucleic acids being degraded by nucleases in the serum. Most conventional cancer gene therapies only target cancer cells and do not appear to be sufficintly efficient to pass clinical trials. Accumulating evidence has shown that extending the therapeutic strategies to the tumor microenvironment, rather than the tumor cell itself, can allow more options for achieving robust anti‐cancer efficiency. In addition, unusual features between tumor microenvironment and normal tissues, such as a lower pH, higher glutathione and reactive oxygen species concentrations, and overexpression of some enzymes, facilitate the design of smart stimuli‐responsive gene carriers regulated by the tumor microenvironment. These carriers interact with nucleic acids and then form stable nanoparticles under physiological conditions. By regulation of the tumor microenvironment, stimuli‐responsive gene carriers are able to change their properties and achieve high gene delivery efficiency. Considering the tumor microenvironment as the “regulator” and “target” when designing gene carriers and choosing therapeutic genes shows significant benefit with respect to improving the accuracy and efficiency of cancer gene therapy.  相似文献   

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Since 1989, efforts to understand the nature of interfirm resource sharing in the form of industrial symbiosis and to replicate in a deliberate way what was largely self‐organizing in Kalundborg, Denmark have followed many paths, some with much success and some with very little. This article provides a historical view of the motivations and means for pursuing industrial symbiosis—defined to include physical exchanges of materials, energy, water, and by‐products among diversified clusters of firms. It finds that “uncovering” existing symbioses has led to more sustainable industrial development than attempts to design and build eco‐industrial parks incorporating physical exchanges. By examining 15 proposed projects brought to national and international attention by the U.S. President's Council on Sustainable Development beginning in the early 1990s, and contrasting these with another 12 projects observed to share more elements of self‐organization, recommendations are offered to stimulate the identification and uncovering of already existing “kernels” of symbiosis. In addition, policies and practices are suggested to identify early‐stage precursors of potentially larger symbioses that can be nurtured and developed further. The article concludes that environmentally and economically desirable symbiotic exchanges are all around us and now we must shift our gaze to find and foster them.  相似文献   

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The transdiagnostic expression of psychotic experiences in common mental disorder (anxiety/depression/substance use disorder) is associated with a poorer prognosis, and a small minority of people may indeed develop a clinical picture that meets criteria for schizophrenia. However, it appears neither useful nor valid to observe early states of multidimensional psychopathology in young people through the “schizo”‐prism, and apply misleadingly simple, unnecessary and inefficient binary concepts of “risk” and “transition”. A review of the “ultra‐high risk” (UHR) or “clinical high risk” (CHR) literature indicates that UHR/CHR samples are highly heterogeneous and represent individuals diagnosed with common mental disorder (anxiety/depression/substance use disorder) and a degree of psychotic experiences. Epidemiological research has shown that psychotic experiences are a (possibly non‐causal) marker of the severity of multidimensional psychopathology, driving poor outcome, yet notions of “risk” and “transition” in UHR/CHR research are restrictively defined on the basis of positive psychotic phenomena alone, ignoring how baseline differences in multidimensional psychopathology may differentially impact course and outcome. The concepts of “risk” and “transition” in UHR/CHR research are measured on the same dimensional scale, yet are used to produce artificial diagnostic shifts. In fact, “transition” in UHR/CHR research occurs mainly as a function of variable sample enrichment strategies rather than the UHR/CHR “criteria” themselves. Furthermore, transition rates in UHR/CHR research are inflated as they do not exclude false positives associated with the natural fluctuation of dimensional expression of psychosis. Biological associations with “transition” thus likely represent false positive findings, as was the initial claim of strong effects of omega‐3 polyunsatured fatty acids in UHR samples. A large body of UHR/CHR intervention research has focused on the questionable outcome of “transition”, which shows lack of correlation with functional outcome. It may be more productive to consider the full range of person‐specific psychopathology in all young individuals who seek help for mental health problems, instead of “policing” youngsters for the transdiagnostic dimension of psychosis. Instead of the relatively inefficient medical high‐risk approach, a public health perspective, focusing on improved access to a low‐stigma, high‐hope, small scale and youth‐specific environment with acceptable language and interventions may represent a more useful and efficient strategy.  相似文献   

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Micro-File film (Eastman Kodak Co.) gave excellent results when used for photomicrography. A 35 mm. reflex camera attached to one tube of a binocular microscope provided a convenient means of recording cells of special interest in chromosome studies. Micro-File was found to give better contrast than Plus-X and required less processing time.  相似文献   

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In an observational study on semi-free Barbary macaques it was investigated whether the phylogenetic roots of human laughter and smile can be traced back to the genus Macaca. On the basis of morphological similarity a ‘relaxed open-mouth display’ as the phylogenetic precursor of the laughter, and a ‘silent bared-teeth display’ as the possible ancestor of the smile can be distinguished in the repertory of the Barbary macaque. Behavioural sequences from focal animal protocols were analyzed in order to establish message and meaning of both displays. Relaxed open-mouth display is regularly observed in the play interactions of juveniles. It is associated with partner-directed behaviour, it is frequently answered by a relaxed open-mouth display of the receiver, and accompanied by a special vocalization. Although up to 50% of the juvenile's play partners were higher ranking than themselves voluntary participation was the rule. Most characteristically, the behaviour patterns shown by both play partners are highly symmetrical and synchronized. Silent bared-teeth display is typically accompanied by evasive or submissive body movements, and occurs primarily in dyadic interactions, mainly by the lower ranking individual. It is not an unidirectional sign of a linear dominance hierarchy, though. Silent bared-teeth display is a frequent answer to aggressive behaviour shown by the receiver. After its performance, an increase of body contact between sender and receiver was observed. Behavioural sequences of senders and receivers are complementary, but lose their asymmetry after occurrence of the display. It is concluded that these results further support Van Hooff 's (1972) view that human laughter and smile have different phylogenetic roots: while silent bared-teeth display is a signal of submission and appeasement, relaxed open-mouth display is rightly called the ‘play face’, and is an expression of fun.  相似文献   

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Restoration is important in urban areas where habitat destruction is greatest. It incorporates many levels of intervention, with creation of new habitat the most extreme form. Most research on habitat creation has been terrestrial, or in marine habitats dominated by large structuring biota, such as mangroves. Intertidal boulder‐fields in urban areas are vulnerable to disturbances and habitat loss, which adversely affect numerous habitat specialists. This study describes experiments in which quarried stones were used to create new habitat outside natural boulder‐fields as a practical approach to restoring habitat. Colonization by specialist fauna and by common algae and invertebrates was measured for a year after deployment. Despite sessile assemblages on new boulders differing from those on natural boulders, common and rare animals rapidly colonized the new habitat. There was no clear succession, but colonization was variable and patchy at all scales examined, although diversities and abundances of some species in this novel habitat matched those of natural boulders within a few months. Rare and common animals generally colonized the new habitat as adults moving in from surrounding areas. Creating new boulder‐fields using quarried rocks is a successful approach to restoration and conservation of fauna where natural boulder‐fields are threatened.  相似文献   

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