Members of the Wg/Wnt family provide key intercellular signals during embryonic development and in the maintenance of homeostatic processes, but critical aspects of their signal transduction pathways remain controversial. We have found that canonical Wg signaling in Drosophila involves distinct initiation and amplification steps, both of which require Arrow/LRP. Expressing a chimeric Frizzled2-Arrow protein in flies that lack endogenous Wg or Arrow showed that this construct functions as an activated Wg receptor but is deficient in signal amplification. In contrast, a chimeric Arrow protein containing the dimerization domain of Torso acted as a potent amplifier of Wg signaling but could not initiate Wg signaling on its own. The two chimeric proteins synergized, so that their co-expression largely reconstituted the signaling levels achieved by expressing Wg itself. The amplification function of Arrow/LRP appears to be particularly important for long-range signaling, and may reflect a general mechanism for potentiating signals in the shallow part of a morphogen gradient. 相似文献
Many studies have suggested the involvement of wild-type (wt) p53 in the repair of DNA double-strand breaks (DSBs) via DNA end-joining (EJ) process. To investigate this possibility, we compared the capacity and fidelity of DNA EJ in RKO cells containing wt p53 and RKO cells containing no p53 (RKO cells with p53 knockdown). The p53 knockdown cells showed lower fidelity of DNA EJ compared to the control RKO cells. The DNA end-protection assay revealed the association of a protein complex including heterogeneous nuclear ribonucleoprotein G (hnRNP G) with the DNA ends in RKO cells containing wt p53, but not with the DNA ends in RKO cells with p53 knockdown. Depletion of endogenous hnRNP G notably diminished the fidelity of EJ in RKO cells expressing wt p53. Moreover, an ectopic expression of hnRNP G significantly enhanced the fidelity of DNA EJ and the protection of DNA ends in human cancer cells lacking hnRNP G protein or containing mutant hnRNP G. Finally, using recombinant hnRNP G proteins, we demonstrated the hnRNP G protein is able to bind to and protect DNA ends from degradation of nucleases. Our results suggest that wt p53 modulates DNA DSB repair by, in part, inducing hnRNP G, and the ability of hnRNP G to bind and protect DNA ends may contribute its ability to promote the fidelity of DNA EJ. 相似文献
Archaeal communities in arable soils are dominated by Nitrososphaeria, a class within Thaumarchaeota comprising all known ammonia-oxidizing archaea (AOA). AOA are key players in the nitrogen cycle and defining their niche specialization can help predicting effects of environmental change on these communities. However, hierarchical effects of environmental filters on AOA and the delineation of niche preferences of nitrososphaerial lineages remain poorly understood. We used phylogenetic information at fine scale and machine learning approaches to identify climatic, edaphic and geomorphological drivers of Nitrososphaeria and other archaea along a 3000 km European gradient. Only limited insights into the ecology of the low-abundant archaeal classes could be inferred, but our analyses underlined the multifactorial nature of niche differentiation within Nitrososphaeria. Mean annual temperature, C:N ratio and pH were the best predictors of their diversity, evenness and distribution. Thresholds in the predictions could be defined for C:N ratio and cation exchange capacity. Furthermore, multiple, independent and recent specializations to soil pH were detected in the Nitrososphaeria phylogeny. The coexistence of widespread ecophysiological differences between closely related soil Nitrososphaeria highlights that their ecology is best studied at fine phylogenetic scale. 相似文献
Phenotypic plasticity is an important mechanism for populations to respond to fluctuating environments, yet may be insufficient to adapt to a directionally changing environment. To study whether plasticity can evolve under current climate change, we quantified selection and genetic variation in both the elevation (RNE) and slope (RNS) of the breeding time reaction norm in a long‐term (1973–2016) study population of great tits (Parus major). The optimal RNE (the caterpillar biomass peak date regressed against the temperature used as cue by great tits) changed over time, whereas the optimal RNS did not. Concordantly, we found strong directional selection on RNE, but not RNS, of egg‐laying date in the second third of the study period; this selection subsequently waned, potentially due to increased between‐year variability in optimal laying dates. We found individual and additive genetic variation in RNE but, contrary to previous studies on our population, not in RNS. The predicted and observed evolutionary change in RNE was, however, marginal, due to low heritability and the sex limitation of laying date. We conclude that adaptation to climate change can only occur via micro‐evolution of RNE, but this will necessarily be slow and potentially hampered by increased variability in phenotypic optima. 相似文献
Even though the idea that modes of speciation other than allopatric speciation are possible in nature is now widespread, compelling examples of ecological speciation in sympatry remain rare. We studied an undescribed radiation of haplochromine cichlids in a young crater lake in western Uganda, and in the small river that is nearby but has currently no known surface connection to the lake. We describe two different modes of speciation that occurred in this cichlid lineage within the past 1,500–10,000 years. Not constrained by gene flow, allopatric divergence between river and lake cichlids affects many different morphological traits as well as nuptial colouration—muted in the river, but intensified and polymorphic in lake cichlids—and neutral genetic differentiation. More surprisingly, we demonstrate a case for sympatric speciation within the small lake that is associated with dramatic differences in male breeding colouration (yellow with bright red-chest versus bright blue) and subtle differences in microhabitat, feeding regime and morphology. Reproductive isolation by assortative mating is suggested by significant differentiation between yellow and blue males in neutral markers of gene flow despite complete sympatry. We hypothesize speciation is mediated by divergent selection on sexual signalling between microhabitats.
In this study, we developed a microfluidics method, using a so-called H-cell microfluidics device, for the determination of protein diffusion coefficients at different concentrations, pHs, ionic strengths, and solvent viscosities. Protein transfer takes place in the H-cell channels between two laminarly flowing streams with each containing a different initial protein concentration. The protein diffusion coefficients are calculated based on the measured protein mass transfer, the channel dimensions, and the contact time between the two streams. The diffusion rates of lysozyme, cytochrome c, myoglobin, ovalbumin, bovine serum albumin, and etanercept were investigated. The accuracy of the presented methodology was demonstrated by comparing the measured diffusion coefficients with literature values measured under similar solvent conditions using other techniques. At low pH and ionic strength, the measured lysozyme diffusion coefficient increased with the protein concentration gradient, suggesting stronger and more frequent intermolecular interactions. At comparable concentration gradients, the measured lysozyme diffusion coefficient decreased drastically as a function of increasing ionic strength (from zero onwards) and increasing medium viscosity. Additionally, a particle tracing numerical simulation was performed to achieve a better understanding of the macromolecular displacement in the H-cell microchannels. It was found that particle transfer between the two channels tends to speed up at low ionic strength and high concentration gradient. This confirms the corresponding experimental observation of protein diffusion measured via the H-cell microfluidics. 相似文献
Plants balance the allocation of resources between growth and defence to optimize fitness in a competitive environment. Perception of neighbour‐detection cues, such as a low ratio of red to far‐red (R:FR) radiation, activates a suite of shade‐avoidance responses that include stem elongation and upward leaf movement, whilst simultaneously downregulating defence. This downregulation is hypothesized to benefit the plant either by mediating the growth‐defence balance in favour of growth in high plant densities or, alternatively, by mediating defence of individual leaves such that those most photosynthetically productive are best protected. To test these hypotheses, we used a 3D functional–structural plant model of Brassica nigra that mechanistically simulates the interactions between plant architecture, herbivory, and the light environment. Our results show that plant‐level defence expression is a strong determinant of plant fitness and that leaf‐level defence mediation by R:FR can provide a fitness benefit in high densities. However, optimal plant‐level defence expression does not decrease monotonically with plant density, indicating that R:FR mediation of defence alone is not enough to optimize defence between densities. Therefore, assessing the ecological significance of R:FR‐mediated defence is paramount to better understand the evolution of this physiological linkage and its implications for crop breeding. 相似文献
Antimicrobial resistance presents a significant health care crisis. The mutation F98Y in Staphylococcus aureus dihydrofolate reductase (SaDHFR) confers resistance to the clinically important antifolate trimethoprim (TMP). Propargyl-linked antifolates (PLAs), next generation DHFR inhibitors, are much more resilient than TMP against this F98Y variant, yet this F98Y substitution still reduces efficacy of these agents. Surprisingly, differences in the enantiomeric configuration at the stereogenic center of PLAs influence the isomeric state of the NADPH cofactor. To understand the molecular basis of F98Y-mediated resistance and how PLAs’ inhibition drives NADPH isomeric states, we used protein design algorithms in the osprey protein design software suite to analyze a comprehensive suite of structural, biophysical, biochemical, and computational data. Here, we present a model showing how F98Y SaDHFR exploits a different anomeric configuration of NADPH to evade certain PLAs’ inhibition, while other PLAs remain unaffected by this resistance mechanism. 相似文献
Abstract An extensive literature survey of the host-range of Agrobacterium -induced neoplasms has revealed that highly susceptible plant families are accumulators of polyphenolics, whereas families assumed to be non-sensitive to the pathogen seem to lack this property. These and other results might indicate that polyphenolics play a role in the host-pathogen relationship of Agrobacterium -induced neoplasms. This hypothesis will be discussed in the light of the present knowledge of crown gall/hairy root induction and progress in plants. 相似文献