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91.
Mark Lipson Po-Ru Loh Sriram Sankararaman Nick Patterson Bonnie Berger David Reich 《PLoS genetics》2015,11(11)
The human mutation rate is an essential parameter for studying the evolution of our species, interpreting present-day genetic variation, and understanding the incidence of genetic disease. Nevertheless, our current estimates of the rate are uncertain. Most notably, recent approaches based on counting de novo mutations in family pedigrees have yielded significantly smaller values than classical methods based on sequence divergence. Here, we propose a new method that uses the fine-scale human recombination map to calibrate the rate of accumulation of mutations. By comparing local heterozygosity levels in diploid genomes to the genetic distance scale over which these levels change, we are able to estimate a long-term mutation rate averaged over hundreds or thousands of generations. We infer a rate of 1.61 ± 0.13 × 10−8 mutations per base per generation, which falls in between phylogenetic and pedigree-based estimates, and we suggest possible mechanisms to reconcile our estimate with previous studies. Our results support intermediate-age divergences among human populations and between humans and other great apes. 相似文献
92.
Avdi NJ Nick JA Whitlock BB Billstrom MA Henson PM Johnson GL Worthen GS 《The Journal of biological chemistry》2001,276(3):2189-2199
The intensity and duration of an inflammatory response depends on the balance of factors that favor perpetuation versus resolution. At sites of inflammation, neutrophils adherent to other cells or matrix components are exposed to tumor necrosis factor-alpha (TNFalpha). Although TNFalpha has been implicated in induction of pro-inflammatory responses, it may also inhibit the intensity of neutrophilic inflammation by promoting apoptosis. Since TNFalpha is not only an important activator of the stress-induced pathways leading to p38 MAPk and c-Jun N-terminal kinase (JNK) but also a potent effector of apoptosis, we investigated the effects of TNFalpha on the JNK pathway in adherent human neutrophils and the potential involvement of this pathway in neutrophil apoptosis. Stimulation with TNFalpha was found to result in beta2 integrin-mediated activation of the cytoplasmic tyrosine kinases Pyk2 and Syk, and activation of a three-part MAPk module composed of MEKK1, MKK7, and/or MKK4 and JNK1. JNK activation was attenuated by blocking antibodies to beta2 integrins, the tyrosine kinase inhibitors, genistein, and tyrphostin A9, a Pyk2-specific inhibitor, and piceatannol, a Syk-specific inhibitor. Exposure of adherent neutrophils to TNFalpha led to the rapid onset of apoptosis that was demonstrated by augmented annexin V binding and caspase-3 cleavage. TNFalpha-induced increases in annexin V binding to neutrophils were attenuated by blocking antibodies to beta2 integrins, and the caspase-3 cleavage was attenuated by tyrphostin A9. Hence, exposure of adherent neutrophils to TNFalpha leads to utilization of the JNK-signaling pathways that may contribute to diverse functional responses including induction of apoptosis and subsequent resolution of the inflammatory response. 相似文献
93.
94.
To examine the effect of ontogeny on metabolic depression in the cunner (Tautogolabrus adspersus), and to understand how ontogeny and the ability to metabolically depress influence this species'' upper thermal tolerance: 1) the metabolic rate of 9°C-acclimated cunner of three size classes [0.2–0.5 g, young of the year (YOY); 3–6 g, small; and 80–120 g, large (adult)] was measured during a 2°C per day decrease in temperature; and 2) the metabolic response of the same three size classes of cunner to an acute thermal challenge [2°C h−1 from 10°C until Critical Thermal Maximum, CTMax] was examined, and compared to that of the Atlantic cod (Gadus morhua). The onset-temperature for metabolic depression in cunner increased with body size, i.e. from 5°C in YOY cunner to 7°C in adults. In contrast, the extent of metabolic depression was ∼80% (Q10 = ∼15) for YOY fish, ∼65% (Q10 = ∼8) for small fish and ∼55% (Q10 = ∼5) for adults, and this resulted in the metabolic scaling exponent (b) gradually increasing from 0.84 to 0.92 between 9°C to 1°C. All size classes of cunner had significantly (approximately 60%) lower routine metabolic rates at 10°C than Atlantic cod. However, there was no species'' difference in the temperature-induced maximum metabolic rate, and this resulted in factorial metabolic scope values that were more than two-fold greater for cunner, and CTMax values that were 6–9°C higher (∼21 vs. 28°C). These results: 1) show that ontogeny influences the temperature of initiation and the extent of metabolic depression in cunner, but not O2 consumption when in a hypometabolic state; and 2) suggest that the evolution of cold-induced metabolic depression in this northern wrasse species has not resulted in a trade-off with upper thermal tolerance, but instead, an enhancement of this species'' metabolic plasticity. 相似文献
95.
Royd Vinya Yadvinder Malhi Nick Brown Joshua B. Fisher 《Acta Physiologiae Plantarum》2012,34(5):1701-1710
We investigated functional coordination between branch hydraulic properties and leaf functional traits among nine miombo woodlands canopy tree species differing in habitat preference and phenology. Specifically, we were seeking to answer the question: are branch hydraulic properties coordinated with leaf functional traits linked to plant drought tolerance in seasonally dry tropical forests and what are the implications for species habitat preference? The hydraulic properties investigated in this study were stem area specific hydraulic conductivity (K S), Huber value (H v), and xylem cavitation vulnerability (??50). The leaf functional traits measured were specific leaf area (SLA), leaf dry matter content (LDMC), and mean leaf area (MLA). Generalists displayed significantly (P?<?0.05) higher cavitation resistance (??50) and SLA, but lower sapwood specific hydraulic conductivity (K S), leaf specific conductivity (K L), MLA, and LDMC than mesic specialists. Although MLA was uncorrelated with ??50, we found significant (P?<?0.05) positive and negative correlations between plant hydraulic properties and leaf functional traits linked to plant drought tolerance ability, indicating that the interactions between branch hydraulics and leaf functional traits related to plant drought tolerance ability may influence tree species habitat preference in water-limited ecosystems. 相似文献
96.
Russell Dinnage Marc W. Cadotte Nick M. Haddad Gregory M. Crutsinger David Tilman 《Ecology letters》2012,15(11):1308-1317
Large‐scale habitat destruction and climate change result in the non‐random loss of evolutionary lineages, reducing the amount of evolutionary history represented in ecological communities. Yet, we have limited understanding of the consequences of evolutionary history on the structure of food webs and the services provided by biological communities. Drawing on 11 years of data from a long‐term plant diversity experiment, we show that evolutionary history of plant communities – measured as phylogenetic diversity – strongly predicts diversity and abundance of herbivorous and predatory arthropods. Effects of plant species richness on arthropods become stronger when phylogenetic diversity is high. Plant phylogenetic diversity explains predator and parasitoid richness as strongly as it does herbivore richness. Our findings indicate that accounting for evolutionary relationships is critical to understanding the severity of species loss for food webs and ecosystems, and for developing conservation and restoration policies. 相似文献
97.
Maggy Jennings David B. Morton Emmanuelle Charton Jane Cooper Coenraad Hendriksen Stella Martin Michael C. Pearce Scott Price Keith Redhead Nick Reed Hugh Simmons Stephen Spencer Hilary Willingale 《Biologicals》2010,38(6):684-695
This report aims to facilitate the implementation of the Three Rs (reduction, refinement and replacement) in the testing of vaccines for regulatory and other purposes. The focus is predominantly on identification of reduction and refinement opportunities in batch potency testing but the principles described are widely applicable to other situations that involve experimental infections of animals. The report should also help to interpret the requirements of the European Pharmacopoeia with regard to the use of alternative tests, humane endpoints and other refinements. Two specific worked examples, for batch potency testing of Clostridium chauvoei and canine leptospira, with recommendations for harmonisation of international test requirements for these and other vaccines, are provided as appendices online. 相似文献
98.
Severe global DNA hypomethylation blocks differentiation and induces histone hyperacetylation in embryonic stem cells 总被引:16,自引:0,他引:16 下载免费PDF全文
Jackson M Krassowska A Gilbert N Chevassut T Forrester L Ansell J Ramsahoye B 《Molecular and cellular biology》2004,24(20):8862-8871
It has been reported that DNA methyltransferase 1-deficient (Dnmt1-/-) embryonic stem (ES) cells are hypomethylated (20% CpG methylation) and die through apoptosis when induced to differentiate. Here, we show that Dnmt[3a-/-,3b-/-] ES cells with just 0.6% of their CpG dinucleotides behave differently: the majority of cells within the culture are partially or completely blocked in their ability to initiate differentiation, remaining viable while retaining the stem cell characteristics of alkaline phosphatase and Oct4 expression. Restoration of DNA methylation levels rescues these defects. Severely hypomethylated Dnmt[3a-/-,3b-/-] ES cells have increased histone acetylation levels, and those cells that can differentiate aberrantly express extraembryonic markers of differentiation. Dnmt[3a-/-,3b-/-] ES cells with >10% CpG methylation are able to terminally differentiate, whereas Dnmt1-/- ES cells with 20% of the CpG methylated cannot differentiate. This demonstrates that successful terminal differentiation is not dependent simply on adequate methylation levels. There is an absolute requirement that the methylation be delivered by the maintenance enzyme Dnmt1. 相似文献
99.
100.
McCormack Sarah A. Ostle Nick Bardgett Richard D. Hopkins David W. Pereira M. Glória Vanbergen Adam J. 《Plant and Soil》2019,437(1-2):341-354
Plant and Soil - Shifts of plant community composition with enhanced atmospheric nitrogen (N) deposition in grasslands have occurred globally. Despite extensive studies on the effects of enhanced N... 相似文献