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71.
Life‐history theory assumes that reproduction and lifespan are constrained by trade‐offs which prevent their simultaneous increase. Recently, there has been considerable interest in the possibility that this cost of reproduction is mediated by oxidative stress. However, empirical tests of this theory have yielded equivocal support. We carried out a meta‐analysis to examine associations between reproduction and oxidative damage across markers and tissues. We show that oxidative damage is positively associated with reproductive effort across females of various species. Yet paradoxically, categorical comparisons of breeders versus non‐breeders reveal that transition to the reproductive state is associated with a step‐change reduction in oxidative damage in certain tissues and markers. Developing offspring may be particularly sensitive to harm caused by oxidative damage in mothers. Therefore, such reductions could potentially function to shield reproducing mothers, gametes and developing offspring from oxidative insults that inevitably increase as a consequence of reproductive effort. According to this perspective, we hypothesise that the cost of reproduction is mediated by dual impacts of maternally‐derived oxidative damage on mothers and offspring, and that mothers may be selected to diminish such damage. Such oxidative shielding may explain why many existing studies have concluded that reproduction has little or no oxidative cost. Future advance in life‐history theory therefore needs to take account of potential transgenerational impacts of the mechanisms underlying life‐history trade‐offs.  相似文献   
72.
A wealth of evidence supports the broad therapeutic potential of NF‐κB and EZH2 inhibitors as adjuvants for breast cancer treatment. We contribute to this knowledge by elucidating, for the first time, unique regulatory crosstalk between EZH2, NF‐κB and the NF‐κB interacting long non‐coding RNA (NKILA). We define a novel signaling loop encompassing canonical and non‐canonical actions of EZH2 on the regulation of NF‐κB/NKILA homeostasis, with relevance to breast cancer treatment. We applied a respective silencing approach in non‐transformed breast epithelial cells, triple negative MDA‐MB‐231 cells and hormone responsive MCF‐7 cells, and measured changes in EZH2/NF‐κB/NKILA levels to confirm their interdependence. We demonstrate cell line‐specific fluctuations in these factors that functionally contribute to epithelial‐to‐mesenchymal transition (EMT) remodelling and cell fate response. EZH2 inhibition attenuates MDA‐MB‐231 cell motility and CDK4‐mediated MCF‐7 cell cycle regulation, while inducing global H3K27 methylation and an EMT phenotype in non‐transformed cells. Notably, these events are mediated by a cell‐context dependent gain or loss of NKILA and NF‐κB. Depletion of NF‐κB in non‐transformed cells enhances their sensitivity to growth factor signaling and suggests a role for the host microenvironment milieu in regulating EZH2/NF‐κB/NKILA homeostasis. Taken together, this knowledge critically informs the delivery and assessment of EZH2 inhibitors in breast cancer.  相似文献   
73.
Nonfullerene acceptors (NFAs) dominate organic photovoltaic (OPV) research due to their promising efficiencies and stabilities. However, there is very little investigation into the molecular processes of degradation, which is critical to guiding design of novel NFAs for long‐lived, commercially viable OPVs. Here, the important role of molecular structure and conformation in NFA photostability in air is investigated by comparing structurally similar but conformationally different promising NFAs: planar O‐IDTBR and nonplanar O‐IDFBR. A three‐phase degradation process is identified: i) initial photoinduced conformational change (i.e., torsion about the core–benzothiadiazole dihedral), induced by noncovalent interactions with environmental molecules, ii) followed by photo‐oxidation and fragmentation, leading to chromophore bleaching and degradation product formation, and iii) finally complete chromophore bleaching. Initial conformational change is a critical prerequisite for further degradation, providing fundamental understanding of the relative stability of IDTBR and IDFBR, where the already twisted IDFBR is more prone to degradation. When blended with the donor polymer poly(3‐hexylthiophene), both NFAs exhibit improved photostability while the photostability of the polymer itself is significantly reduced by the more miscible twisted NFA. The findings elucidate the important role of NFA molecular structure in photostability of OPV systems, and provide vital insights into molecular design rules for intrinsically photostable NFAs.  相似文献   
74.
Here, it is investigated whether an energetic cascade between mixed and pure regions assists in suppressing recombination losses in non‐fullerene acceptor (NFA)‐based organic solar cells. The impact of polymer‐NFA blend composition upon morphology, energetics, charge carrier recombination kinetics, and photocurrent properties are studied. By changing film composition, morphological structures are varied from consisting of highly intermixed polymer‐NFA phases to consisting of both intermixed and pure phase. Cyclic voltammetry is employed to investigate the impact of blend morphology upon NFA lowest unoccupied molecular orbital (LUMO) level energetics. Transient absorption spectroscopy reveals the importance of an energetic cascade between mixed and pure phases in the electron–hole dynamics in order to well separate spatially localized electron–hole pairs. Raman spectroscopy is used to investigate the origin of energetic shift of NFA LUMO levels. It appears that the increase in NFA electron affinity in pure phases relative to mixed phases is correlated with a transition from a relatively planar backbone structure of NFA in pure, aggregated phases, to a more twisted structure in molecularly mixed phases. The studies focus on addressing whether aggregation‐dependent acceptor LUMO level energetics are a general design requirement for both fullerene and NFAs, and quantifying the magnitude, origin, and impact of such energetic shifts upon device performance.  相似文献   
75.
When considering the large‐scale deployment of bioenergy crops, it is important to understand the implication for ecosystem hydrological processes and the influences of crop type and location. Based on the potential for future land use change (LUC), the 10,280 km2 West Wales Water Framework Directive River Basin District (UK) was selected as a typical grassland dominated district, and the Soil & Water Assessment Tool (SWAT) hydrology model with a geographic information systems interface was used to investigate implications for different bioenergy deployment scenarios. The study area was delineated into 855 sub‐basins and 7,108 hydrological response units based on rivers, soil type, land use, and slope. Changes in hydrological components for two bioenergy crops (Miscanthus and short rotation coppice, SRC) planted on 50% (2,192 km2) or 25% (1,096 km2) of existing improved pasture are quantified. Across the study area as a whole, only surface run‐off with SRC planted at the 50% level was significantly impacted, where it was reduced by up to 23% (during April). However, results varied spatially and a comparison of annual means for each sub‐basin and scenario revealed surface run‐off was significantly decreased and baseflow significantly increased (by a maximum of 40%) with both Miscanthus and SRC. Evapotranspiration was significantly increased with SRC (at both planting levels) and water yield was significantly reduced with SRC (at the 50% level) by up to 5%. Effects on streamflow were limited, varying between ?5% and +5% change (compared to baseline) in the majority of sub‐basins. The results suggest that for mesic temperate grasslands, adverse effects from the drying of soil and alterations to streamflow may not arise, and with surface run‐off reduced and baseflow increased, there could, depending on crop location, be potential benefits for flood and erosion mitigation.  相似文献   
76.
The lonchaeid fly Silba capsicarum is recorded for the first time from the island of Java where it is considered a potential pest of chilli pepper. The taxonomy and ecology of the species is reviewed and comparisons are drawn with Lonchaeidae attacking Capsicum spp. in the Neotropics. Initial results on the level of infestation in Java are provided.  相似文献   
77.
78.
Peptide O-xylosyltransferase (EC 2.4.2.26) is the first enzyme required for the generation of chondroitin and heparan sulfate glycosaminoglycan chains of proteoglycans. Cloning of cDNAs has previously shown that, whereas invertebrates generally have a single xylosyltransferase gene, vertebrate genomes encode two similar proteins, xylosyltransferase I and II (XT-I and XT-II). To date, enzymatic activity has only been demonstrated for the human XT-I, Caenorhabditis SQV-6, and Drosophila OXT isoforms. In the present study, we demonstrate that a soluble form of human XT-II expressed in the xylosyltransferase-deficient pgsA-745 (S745) Chinese hamster ovary cell line is indeed capable of catalyzing the transfer of xylose to a variety of peptide substrates; its enzyme activity was also proven using a Pichia-expressed form of XT-II. Its pH, temperature, and cation dependences are similar to those of XT-I expressed in either mammalian cells or yeast. Our data suggest that XT-I and XT-II are, at least in vitro, functionally identical.  相似文献   
79.
The role of the fibronectin IGD motif in stimulating fibroblast migration   总被引:1,自引:0,他引:1  
The motogenic activity of migration-stimulating factor, a truncated isoform of fibronectin (FN), has been attributed to the IGD motifs present in its FN type 1 modules. The structure-function relationship of various recombinant IGD-containing FN fragments is now investigated. Their structure is assessed by solution state NMR and their motogenic ability tested on fibroblasts. Even conservative mutations in the IGD motif are inactive or have severely reduced potency, while the structure remains essentially the same. A fragment with two IGD motifs is 100 times more active than a fragment with one and up to 10(6) times more than synthetic tetrapeptides. The wide range of potency in different contexts is discussed in terms of cryptic FN sites and cooperativity. These results give new insight into the stimulation of fibroblast migration by IGD motifs in FN.  相似文献   
80.
The introduction of new approaches for characterizing microbial communities and imaging soil environments has benefited soil microbiology by providing new ways of detecting and locating microorganisms. Consequently, soil microbiology is poised to progress from simply cataloguing microbial complexity to becoming a systems science. A systems approach will enable the structures of microbial communities to be characterized and will inform how microbial communities affect soil function. Systems approaches require accurate analyses of the spatio-temporal properties of the different microenvironments present in soil. In this Review we advocate the need for the convergence of the experimental and theoretical approaches that are used to characterize and model the development of microbial communities in soils.  相似文献   
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