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Central pattern generator (CPG) networks rely on a balance of intrinsic and network properties to produce reliable, repeatable activity patterns. This balance is maintained by homeostatic plasticity where alterations in neuronal properties dynamically maintain appropriate neural output in the face of changing environmental conditions and perturbations. However, it remains unclear just how these neurons and networks can both monitor their ongoing activity and use this information to elicit homeostatic physiological responses to ensure robustness of output over time. Evidence exists that CPG networks use a mixed strategy of activity‐dependent, activity‐independent, modulator‐dependent, and synaptically regulated homeostatic plasticity to achieve this critical stability. In this review, we focus on some of the current understanding of the molecular pathways and mechanisms responsible for this homeostatic plasticity in the context of central pattern generator function, with a special emphasis on some of the smaller invertebrate networks that have allowed for extensive cellular‐level analyses that have brought recent insights to these questions. 相似文献
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Rana Nicolas Gaëtan Lévêque Pierre-Michel Adam Thomas Maurer 《Plasmonics (Norwell, Mass.)》2018,13(4):1219-1225
Interest in graphene has been widely increasing since its discovery in 2004. Research on graphene for plasmonic applications has also boomed due to the high potential of these systems. In this article, we discuss the possible interaction between metallic NPs and graphene monolayer. We show how the contact between metallic NPs and graphene results in graphene doping. More importantly, we experimentally put into evidence the possible modulation of the plasmonic resonance of NPs by graphene doping. Understanding and evidencing this interaction is highly important both from a fundamental point of view and for specific applications such as active plasmonic devices. 相似文献
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Longer lifespan in male mice treated with a weakly estrogenic agonist,an antioxidant,an α‐glucosidase inhibitor or a Nrf2‐inducer 下载免费PDF全文
Adam Antebi Clinton M. Astle Molly Bogue Martin S. Denzel Elizabeth Fernandez Kevin Flurkey Karyn L. Hamilton Dudley W. Lamming Martin A. Javors João Pedro de Magalhães Paul Anthony Martinez Joe M. McCord Benjamin F. Miller Michael Müller James F. Nelson Juliet Ndukum G. Ed. Rainger Arlan Richardson David M. Sabatini Adam B. Salmon James W. Simpkins Wilma T. Steegenga Nancy L. Nadon David E. Harrison 《Aging cell》2016,15(5):872-884
The National Institute on Aging Interventions Testing Program (ITP) evaluates agents hypothesized to increase healthy lifespan in genetically heterogeneous mice. Each compound is tested in parallel at three sites, and all results are published. We report the effects of lifelong treatment of mice with four agents not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) and metformin – the latter with and without rapamycin, and two drugs previously examined: 17‐α‐estradiol and nordihydroguaiaretic acid (NDGA), at doses greater and less than used previously. 17‐α‐estradiol at a threefold higher dose robustly extended both median and maximal lifespan, but still only in males. The male‐specific extension of median lifespan by NDGA was replicated at the original dose, and using doses threefold lower and higher. The effects of NDGA were dose dependent and male specific but without an effect on maximal lifespan. Protandim, a mixture of botanical extracts that activate Nrf2, extended median lifespan in males only. Metformin alone, at a dose of 0.1% in the diet, did not significantly extend lifespan. Metformin (0.1%) combined with rapamycin (14 ppm) robustly extended lifespan, suggestive of an added benefit, based on historical comparison with earlier studies of rapamycin given alone. The α‐glucosidase inhibitor, acarbose, at a concentration previously tested (1000 ppm), significantly increased median longevity in males and 90th percentile lifespan in both sexes, even when treatment was started at 16 months. Neither fish oil nor UDCA extended lifespan. These results underscore the reproducibility of ITP longevity studies and illustrate the importance of identifying optimal doses in lifespan studies. 相似文献
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Magdalena Wysocka Anna Wojtysiak Małgorzata Okońska Natalia Gruba Mirosław Jarząb Tomasz Wenta Barbara Lipińska Reneta Grzywa Marcin Sieńczyk Krzysztof Rolka Adam Lesner 《Analytical biochemistry》2015
HtrA2 belongs to the HtrA (high temperature requirement A) family of ATP-independent serine proteases. The primary function of HtrA2 includes maintaining the mitochondria homeostasis, cell death (by apoptosis, necrosis, or anoikis), and contribution to the cell signaling. Several recent reports have shown involvement of HtrA2 in development of cancer and neurodegenerative disorders. Here, we describe the profiling of HtrA2 protease substrate specificity via the combinatorial chemistry approach that led to the selection of novel intramolecularly quenched substrates. For all synthesized compounds, the highest HtrA2-mediated hydrolysis efficiency and selectivity among tested HtrA family members was observed for ABZ-Ile-Met-Thr-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2, which displayed a specificity constant kcat/KM value of 14,535 M−1 s−1. 相似文献
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Qingping Xu Matthew Biancalana Joanna C. Grant Hsiu‐Ju Chiu Lukasz Jaroszewski Mark W. Knuth Scott A. Lesley Adam Godzik Marc‐Andr Elsliger Ashley M. Deacon Ian A. Wilson 《Protein science : a publication of the Protein Society》2019,28(9):1676-1689
Free‐standing single‐layer β‐sheets are extremely rare in naturally occurring proteins, even though β‐sheet motifs are ubiquitous. Here we report the crystal structures of three homologous, single‐layer, anti‐parallel β‐sheet proteins, comprised of three or four twisted β‐hairpin repeats. The structures reveal that, in addition to the hydrogen bond network characteristic of β‐sheets, additional hydrophobic interactions mediated by small clusters of residues adjacent to the turns likely play a significant role in the structural stability and compensate for the lack of a compact hydrophobic core. These structures enabled identification of a family of secreted proteins that are broadly distributed in bacteria from the human gut microbiome and are putatively involved in the metabolism of complex carbohydrates. A conserved surface patch, rich in solvent‐exposed tyrosine residues, was identified on the concave surface of the β‐sheet. These new modular single‐layer β‐sheet proteins may serve as a new model system for studying folding and design of β‐rich proteins. 相似文献
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