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Chemically modified antisense oligonucleotides (ASOs) are widely used as a tool to functionalize microRNAs (miRNAs). Reduction of miRNA level after ASO inhibition is commonly reported to show efficacy. Whether this is the most relevant endpoint for measuring miRNA inhibition has not been adequately addressed in the field although it has important implications for evaluating miRNA targeting studies. Using a novel approach to quantitate miRNA levels in the presence of excess ASO, we have discovered that the outcome of miRNA inhibition can vary depending on the chemical modification of the ASO. Although some miRNA inhibitors cause a decrease in mature miRNA levels, we have identified a novel 2′-fluoro/2′-methoxyethyl modified ASO motif with dramatically improved in vivo potency which does not. These studies show there are multiple mechanisms of miRNA inhibition by ASOs and that evaluation of secondary endpoints is crucial for interpreting miRNA inhibition studies.  相似文献   
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A sequence of paleosols in the Solo Basin, Central Java, Indonesia, documents the local and regional environments present when Homo erectus spread through Southeast Asia during the early Pleistocene. The earliest human immigrants encountered a low-relief lake-margin landscape dominated by moist grasslands with open woodlands in the driest landscape positions. By 1.5 Ma, large streams filled the lake and the landscape became more riverine in nature, with riparian forests, savanna, and open woodland. Paleosol morphology and carbon isotope values of soil organic matter and pedogenic carbonates indicate a long-term shift toward regional drying or increased duration of the annual dry season through the early Pleistocene. This suggests that an annual dry season associated with monsoon conditions was an important aspect of the paleoclimate in which early humans spread from Africa to Southeast Asia.  相似文献   
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The mutualism between chemical cues emitted into the air and variations in how primates respond to them using olfaction has demonstrated aspects of species‐specific adaptations. Building on this mutualism we can look at particle deposition as another means to understanding how various environments may have elicited biological changes that enable efficient communication. Research on particle movement and deposition within the nasal cavity is largely based on questions about health as it relates to drug delivery systems and overall olfactory function in modern humans. With increased access to 3D models and the use of computational fluid dynamic analysis, researchers have been able to simulate site‐specific deposition, to determine what particles are making it through the nasal cavity to the main olfactory epithelium, which ultimately leads to processing in the olfactory bulb. Here we discuss particle deposition research, sensory drive and their potential applications to evolutionary anthropology.  相似文献   
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Biodiversity and Conservation - Across Europe, calcareous grasslands become increasingly fragmented and their quality deteriorates through abandonment and land use intensification, both affecting...  相似文献   
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In many aquatic animals, predator avoidance can be stimulated by chemical cues, including those released by injured prey (alarm cues). Alarm cues of both conspecific and heterospecific origin have been identified within several fish taxa, where phylogenetic conservation of the cue-response complex is common. Turbellarian flatworms (planaria) are among the simplest animals known to respond to chemical cues released by injured conspecifics. We examined how two locally sympatric planaria species respond to conspecific and heterospecific chemical cues using macerated tissue suspensions. Brown (Girardia tigrina) and black (Dugesia dorotocephala) planaria both exhibited avoidance behavior when presented conspecific cues. Despite a significant twofold difference in body size (black > brown), stimulus prepared from a single (1×) individual of either species elicited avoidance. Increasing brown planaria cue concentration by macerating two individuals (2×) produced a significant increase in conspecific avoidance. Heterospecific stimuli produced asymmetric results. Black planaria avoided the brown planaria stimulus, but only in the higher concentration (2×) trials. Brown planaria did not consistently exhibit avoidance of the black planaria stimulus and some brown subjects approached and consumed black planarian tissues. Our results expand the demonstrated occurrence of alarm cues among planaria and suggest that avoidance behavior can be mediated by multiple environmental and intrinsic factors in freshwater Turbellaria.  相似文献   
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Local adaptation, adaptive population divergence and speciation are often expected to result from populations evolving in response to spatial variation in selection. Yet, we lack a comprehensive understanding of the major features that characterise the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data set includes 60 studies, consisting of 3937 estimates of selection across an average of five populations. We performed meta‐analyses to explore features characterising spatial variation in directional selection. We found that selection tends to vary mainly in strength and less in direction among populations. Although differences in the direction of selection occur among populations they do so where selection is often weakest, which may limit the potential for ongoing adaptive population divergence. Overall, we also found that spatial variation in selection appears comparable to temporal (annual) variation in selection within populations; however, several deficiencies in available data currently complicate this comparison. We discuss future research needs to further advance our understanding of spatial variation in selection.  相似文献   
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