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1.
Surveying microglia, the resident macrophage‐like cells in the central nervous system, continuously screen their surroundings to sense imbalance in tissue homeostasis. Their activity is tightly regulated in both a pro‐ and anti‐inflammatory manner. We have previously shown that the lipoglycoproteins WNT‐3A and WNT‐5A drive pro‐inflammatory transformation in primary mouse microglia cells, arguing that WNTs have a role in the modulation of the central nervous system immune response. In this study, we address the effects of recombinant WNT‐3A and WNT‐5A on lipopolysaccharide (LPS)‐activated mouse primary microglia to investigate the putative anti‐inflammatory modulation of microglia by WNTs. While both WNT‐3A and WNT‐5A alone induce an up‐regulation of cyclooxygenase 2 (COX2), a generic pro‐inflammatory microglia marker, LPS exceeds these effects dramatically. However, combination of LPS and WNTs results in a dose‐dependent decrease in LPS‐induced cyclooxygenase 2 protein and mRNA expression. In conclusion, our data suggest that WNTs have a dual and context‐dependent effect on microglia acting in a homeostatic pro‐ and anti‐inflammatory manner.  相似文献   

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The virulence–transmission trade‐off hypothesis proposed more than 30 years ago is the cornerstone in the study of host–parasite co‐evolution. This hypothesis rests on the premise that virulence is an unavoidable and increasing cost because the parasite uses host resources to replicate. This cost associated with replication ultimately results in a deceleration in transmission rate because increasing within‐host replication increases host mortality. Empirical tests of predictions of the hypothesis have found mixed support, which cast doubt about its overall generalizability. To quantitatively address this issue, we conducted a meta‐analysis of 29 empirical studies, after reviewing over 6000 published papers, addressing the four core relationships between (1) virulence and recovery rate, (2) within‐host replication rate and virulence, (3) within‐host replication and transmission rate, and (4) virulence and transmission rate. We found strong support for an increasing relationship between replication and virulence, and replication and transmission. Yet, it is still uncertain if these relationships generally decelerate due to high within‐study variability. There was insufficient data to quantitatively test the other two core relationships predicted by the theory. Overall, the results suggest that the current empirical evidence provides partial support for the trade‐off hypothesis, but more work remains to be done.  相似文献   

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A new concept of multiple redox semi‐solid‐liquid (MRSSL) flow battery that takes advantage of active materials in both liquid and solid phases, is proposed and demonstrated. Liquid lithium iodide (LiI) electrolyte and solid sulfur/carbon (S/C) composite, forming LiI‐S/C MRSSL catholyte, are employed to demonstrate this concept. Record volumetric capacity (550 Ah L?1catholyte) is achieved using highly concentrated and synergistic multiple redox reactions of LiI and sulfur. The liquid LiI electrolyte is found to increase the reversible volumetric capacity of the catholyte, improve the electrochemical utilization of the S/C composite, and reduce the viscosity of catholyte. A continuous flow test is demonstrated and the influence of the flow rate on the flow battery performance is discussed. The MRSSL flow battery concept transforms inactive component into bi‐functional active species and creates synergistic interactions between multiple redox couples, offering a new direction and wide‐open opportunities to develop high‐energy‐density flow batteries.  相似文献   

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Abstract In this work we analyse the pollination community in a South American forest known as ‘talar’. This is a vegetal woody community that inhabits fossil coastal banks characterized by seasonal temperate weather and calcareous soil, at the coast of the Río de la Plata, in the province of Buenos Aires, Argentina. We obtained data of the interactions between anthophylous insects and entomophylous flowering plants over an extensive period of time. We showed that pollination system parameters, such as partners’ identity, system size, and connectance, fluctuated among months, when sampled year‐long. Maximal network size occurred in early spring and early autumn, when both the number of mutualistic species and the number of interactions peaked, and this was also when network asymmetry was higher than average. Monthly connectance of the plant‐flower visitor matrix decreased to its lowest values at these peaks. Available data suggest that cumulative traditional connectance (i.e. the connectance calculated as the whole number of interactions registered in the community divided by the full size system) underestimates actual connectance values by a factor of c. 3 ×. Monthly values of connectance decreased exponentially as system size increased, and the distribution of interactions per species followed power‐law regimes for animals, and truncated power‐law regimes for plants, in accordance with patterns previously deduced from among‐network cumulative communities studies. We think that either within or and among pollination networks, systems that are organized as power‐law regimes may be a basic property of these webs, and provide examples of the fact. Both seasonal changes and interactions between mutualists like competition, and some degree of facilitation, may be very important to understand the performance of the system as a whole, and the role and importance of different species in the community. We suggest that communities of plant – pollinators that exhibit extended activity, such as temperate or tropical seasonal ones, should be studied through consecutive plant‐pollinator webs rather than cumulative ones. The partition of the system into smaller serial parts allows us to obtain outstanding information of every short period. This information is flattened by the average effect when we considered the combined analysis of the whole data.  相似文献   

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Light responses mediated by the photoreceptors play crucial roles in regulating different aspects of plant growth and development. An E3 ubiquitin ligase complex CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1)1/SUPPRESSOR OF PHYA (SPA), one of the central repressors of photomorphogenesis, is critical for maintaining skotomorphogenesis. It targets several positive regulators of photomorphogenesis for degradation in darkness. Recently, we revealed that basic helix‐loop‐helix factors, HECATEs (HECs), function as positive regulators of photomorphogenesis by directly interacting and antagonizing the activity of another group of repressors called PHYTOCHROME‐INTERACTING FACTORs (PIFs). It was also shown that HECs are partially degraded in the dark through the ubiquitin/26S proteasome pathway. However, the underlying mechanism of HEC degradation in the dark is still unclear. Here, we show that HECs also interact with both COP1 and SPA proteins in darkness, and that HEC2 is directly targeted by COP1 for degradation via the ubiquitin/26S proteasome pathway. Moreover, COP1‐mediated polyubiquitylation and degradation of HEC2 are enhanced by PIF1. Therefore, the ubiquitylation and subsequent degradation of HECs are significantly reduced in both cop1 and pif mutants. Consistent with this, the hec mutants partially suppress photomorphogenic phenotypes of both cop1 and pifQ mutants. Collectively, our work reveals that the COP1/SPA‐mediated ubiquitylation and degradation of HECs contributes to the coordination of skoto/photomorphogenic development in plants.  相似文献   

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Cilia play a major role in the regulation of numerous signaling pathways and are essential for embryonic development. Mutations in genes affecting ciliary function can cause a variety of diseases in humans summarized as ciliopathies. To facilitate the detection and visualization of cilia in a temporal and spatial manner in mouse tissues, we generated a Cre‐inducible cilium‐specific reporter mouse line expressing an ARL13B‐tRFP fusion protein driven by a CMV enhancer/chicken β actin promotor (pCAG) from the Hprt locus. We detected bright and specific ciliary signals by immunostainings of various mono‐ and multiciliated tissues and by time‐lapse live‐cell analysis of cultured embryos and organ explant cultures. Additionally, we monitored cilium assembly and disassembly in embryonic fibroblast cells using live‐cell imaging. Thus, the ARL13B‐tRFP reporter mouse strain is a valuable tool for the investigation of ciliary structure and function in a tissue‐specific manner to understand processes, such as ciliary protein trafficking or cilium‐dependent signaling in vitro and in vivo.  相似文献   

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Elevated levels of the second messenger cyclic dimeric GMP, c‐di‐GMP, promote transition of bacteria from single motile cells to surface‐attached multicellular communities. Here we describe a post‐translational mechanism by which c‐di‐GMP initiates this transition in enteric bacteria. High levels of c‐di‐GMP induce the counterclockwise bias in Escherichia coli flagellar rotation, which results in smooth swimming. Based on co‐immunoprecipitation, two‐hybrid and mutational analyses, the E. coli c‐di‐GMP receptor YcgR binds to the FliG subunit of the flagellum switch complex, and the YcgR–FliG interaction is strengthened by c‐di‐GMP. The central fragment of FliG binds to YcgR as well as to FliM, suggesting that YcgR–c‐di‐GMP biases flagellum rotation by altering FliG‐FliM interactions. The c‐di‐GMP‐induced smooth swimming promotes trapping of motile bacteria in semi‐solid media and attachment of liquid‐grown bacteria to solid surfaces, whereas c‐di‐GMP‐dependent mechanisms not involving YcgR further facilitate surface attachment. The YcgR–FliG interaction is conserved in the enteric bacteria, and the N‐terminal YcgR/PilZN domain of YcgR is required for this interaction. YcgR joins a growing list of proteins that regulate motility via the FliG subunit of the flagellum switch complex, which suggests that FliG is a common regulatory entryway that operates in parallel with the chemotaxis that utilizes the FliM‐entryway.  相似文献   

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The slow growth‐high mortality hypothesis (SG‐HG) predicts that slower growing herbivores suffer greater mortality due to a prolonged window of vulnerability. Given diverse plant–herbivore–natural enemy systems resulting from different feeding ecologies of herbivores and natural enemies, this hypothesis might not always be applicable to all systems. This is evidenced by mixed support from empirical data. In this study, a meta‐analysis of the SG‐HM hypothesis for insects was conducted, aiming to find conditions that favor or reject SG‐HM. The analysis revealed significant within‐ and between‐group heterogeneity for almost all explanatory variables and overall did not support SG‐HM. In this analysis, SG‐HM was supported when any of the following 5 conditions was met: (1) host food consisted of artificial diet; (2) herbivore growth was measured as larval mass; (3) herbivores were generalists; (4) no or multiple species of natural enemies were involved in the study; and (5) parasitoids (i.e., parasitic insects) involved in the study were gregarious. SG‐HM was rejected when any of the following 5 conditions was met: (1) herbivores were from the order Hymentoptera; (2) parasitoids from more than 1 order caused herbivore mortality; (2) parasitoids were specialists; (3) parasitoids were solitary; (4) parasitoids were idiobionts or koinobionts; and (5) single species of natural enemy caused mortality of specialist herbivores. All known studies investigated herbivore mortality for a short period of their life cycle. Researchers are encouraged to monitor herbivore mortality during the entire window of susceptibility or life cycle using life tables. Studies involving multiple mortality factors (i.e., both biotic and abiotic) or multiple natural enemy species are also encouraged since herbivores in nature face a multitude of risks during the entire life cycle. More comprehensive studies may increase our understanding of factors influencing the relationships between herbivore growth and mortality.  相似文献   

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The Enterobacter cloacae complex (ECC) consists of closely related bacteria commonly associated with the human microbiota. ECC are increasingly isolated from healthcare‐associated infections, demonstrating that these Enterobacteriaceae are emerging nosocomial pathogens. ECC can rapidly acquire multidrug resistance to conventional antibiotics. Cationic antimicrobial peptides (CAMPs) have served as therapeutic alternatives because they target the highly conserved lipid A component of the Gram‐negative outer membrane. Many Enterobacteriaceae fortify their outer membrane with cationic amine‐containing moieties to prevent CAMP binding, which can lead to cell lysis. The PmrAB two‐component system (TCS) directly activates 4‐amino‐4‐deoxy‐l ‐arabinose (l ‐Ara4N) biosynthesis to result in cationic amine moiety addition to lipid A in many Enterobacteriaceae such as E. coli and Salmonella. In contrast, PmrAB is dispensable for CAMP resistance in E. cloacae. Interestingly, some ECC clusters exhibit colistin heteroresistance, where a subpopulation of cells exhibit clinically significant resistance levels compared to the majority population. We demonstrate that E. cloacae lipid A is modified with l ‐Ara4N to induce CAMP heteroresistance and the regulatory mechanism is independent of the PmrABEcl TCS. Instead, PhoPEcl binds to the arnBEcl promoter to induce l ‐Ara4N biosynthesis and PmrAB‐independent addition to the lipid A disaccharolipid. Therefore, PhoPQEcl contributes to regulation of CAMP heteroresistance in some ECC clusters.  相似文献   

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The design of a sodium‐ion rechargeable battery with an antimony anode, a Na3V2(PO4)3 cathode, and a low‐cost composite gel‐polymer electrolyte based on cross‐linked poly(methyl methacrylate) is reported. The application of an antimony anode, on replacement of the sodium metal that is commonly used in sodium‐ion half‐cells, reduces significantly the interfacial resistance and charge transfer resistance of a sodium‐ion battery, which enables a smaller polarization for a sodium‐ion full‐cell Sb/Na3V2(PO4)3 running at relatively high charge and discharge rates. The incorporation of the gel‐polymer electrolyte is beneficial to maintain stable interfaces between the electrolyte and the electrodes of the sodium‐ion battery at elevated temperature. When running at 60 °C, the sodium‐ion full‐cell Sb/Na3V2(PO4)3 with the gel‐polymer electrolyte exhibits superior cycling stability compared to a battery with the conventional liquid electrolyte.  相似文献   

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Energy‐storage technology is moving beyond lithium batteries to sodium as a result of its high abundance and low cost. However, this sensible transition requires the discovery of high‐rate and long‐lifespan anode materials, which remains a significant challenge. Here, the facile synthesis of an amorphous Sn2P2O7/reduced graphene oxide nanocomposite and its sodium storage performance between 0.01 and 3.0 V are reported for the first time. This hybrid electrode delivers a high specific capacity of 480 mA h g?1 at a current density of 50 mA g?1 and superior rate performance of 250 and 165 mA h g?1 at 2 and 10 A g?1, respectively. Strikingly, this anode can sustain 15 000 cycles while retaining over 70% of the initial capacity. Quantitative kinetic analysis reveals that the sodium storage is governed by pseudocapacitance, particularly at high current rates. A full cell with sodium super ionic conductor (NASICON)‐structured Na3V2(PO4)2F3 and Na3V2(PO4)3 as cathodes exhibits a high energy density of over 140 W h kg?1 and a power density of nearly 9000 W kg?1 as well as stability over 1000 cycles. This exceptional performance suggests that the present system is a promising power source for promoting the substantial use of low‐cost energy storage systems.  相似文献   

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With the increasing importance of wireless microelectronic devices the need for on‐board power supplies is evidently also increasing. Possible candidates for microenergy storage devices are planar all‐solid‐state Li‐ion microbatteries, which are currently under development by several start‐up companies. However, to increase the energy density of these microbatteries further and to ensure a high power delivery, three‐dimensional (3D) designs are essential. Therefore, several concepts have been proposed for the design of 3D microbatteries and these are reviewed. In addition, an overview is given of the various electrode and electrolyte materials that are suitable for 3D all‐solid‐state microbatteries. Furthermore, methods are presented to produce films of these materials on a nano‐ and microscale.  相似文献   

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