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61.
J H Gillespie 《Molecular biology and evolution》1989,6(6):636-647
Recent efforts to estimate the index of dispersion [R(t)] of molecular evolution-i.e., the ratio of the variance in the number of substitutions on a lineage to the mean number-have suffered from an inability to adjust the data for lineage effects. These effects may include the generation-time dependency of the rate of evolution or improper assumptions about the branching pattern of a phylogenetic tree. In the present paper a method for correcting for lineage effects in the estimation of R(t) is presented for trees made up of three species. The recent data published by Li et al. for 20 loci in three orders of mammals is examined, and the average R(t), corrected for lineage effects, is shown to be 7.75 for replacement substitutions and 3.3 for silent substitutions. Thus the high values reported earlier may not be dismissed as due to generation-time effects or improper assumptions about phylogenies. Computer simulations are presented to give confidence in the estimate for replacement substitutions but also to demonstrate that the estimate for silent substitutions is sensitive to corrections for multiple substitutions and is not as reliable. This work's implications for our understanding of the mechanism of molecular evolution are discussed, and the arguments in favor of the hypothesis that replacement substitutions are mostly selected while silent substitutions are mostly neutral is presented. 相似文献
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Arnold Gillespie 《BMJ (Clinical research ed.)》1972,1(5793):150-152
The pharmacological phenomena of enhancement and potentiation of uterine response occur respectively when combinations of some prostaglandins and oxytocin are given serially and simultaneously to a patient. Employing these phenomena allows small doses of the drugs to achieve the same effects as a large dose given alone. In a pilot study of the use of the combination of prostaglandin and oxytocin for the induction of mid-trimester abortion seven of nine women were aborted within 48 hours. Side effects attributable to prostaglandin were eliminated or reduced in severity. 相似文献
64.
Sarah E. McDonald Nick Reid Rhiannon Smith Cathleen M. Waters John Hunter Romina Rader 《Austral ecology》2020,45(1):60-69
Continuous livestock grazing can have negative effects on biodiversity and landscape function in arid and semi‐arid rangelands. Alternative grazing management practices, such as rotational grazing, may be a viable option for broad‐scale biodiversity conservation and sustainable pastoral management. This study compared ground cover, plant species composition and floristic and functional diversity along gradients of grazing intensity between a pastoral property rotationally grazed by goats and an adjacent nature reserve (ungrazed by commercial livestock) in semi‐arid south‐eastern Australia. Understorey plant species composition differed significantly between the rotationally grazed property and the nature reserve, with a greater proportion and frequency of palatable species recorded in the nature reserve. Understorey plant species richness, diversity, functional biodiversity measures and ground cover declined with increasing grazing pressure close to water points under commercial rotational grazing management. However, at a whole‐paddock scale, there were few differences in plant biodiversity and ground cover between the rotationally grazed property and the nature reserve, despite differences in overall plant species composition. Flexible, adaptive, rotational grazing should be investigated further for its potential to achieve both socio‐economic and biodiversity conservation outcomes in semi‐arid rangelands to complement existing conservation reserves. 相似文献
65.
Journal of Molecular Histology - The morphological and possible functional interactions between the connective tissue and enamel organ cells were examined during the maturation phase of enamel... 相似文献
66.
John Paul Wanner Roopashree Subbaiah Yelenna Skomorovska-Prokvolit Yousef Shishani Eric Boilard Sujatha Mohan Robert Gillespie Masaru Miyagi Reuben Gobezie 《Arthritis research & therapy》2013,15(6):R180
Introduction
The development of effective treatments for osteoarthritis (OA) has been hampered by a poor understanding of OA at the cellular and molecular levels. Emerging as a disease of the ''whole joint’, the importance of the biochemical contribution of various tissues, including synovium, bone and articular cartilage, has become increasingly significant. Bathing the entire joint structure, the proteomic analysis of synovial fluid (SF) from osteoarthritic shoulders offers a valuable ''snapshot’ of the biologic environment throughout disease progression. The purpose of this study was to identify differentially expressed proteins in early and late shoulder osteoarthritic SF in comparison to healthy SF.Methods
A quantitative 18O labeling proteomic approach was employed to identify the dysregulated SF proteins in early (n = 5) and late (n = 4) OA patients compared to control individuals (n = 5). In addition, ELISA was used to quantify six pro-inflammatory and two anti-inflammatory cytokines.Results
Key results include a greater relative abundance of proteins related to the complement system and the extracellular matrix in SF from both early and late OA. Pathway analyses suggests dysregulation of the acute phase response, liver x receptor/retinoid x receptor (LXR/RXR), complement system and coagulation pathways in both early and late OA. The network related to lipid metabolism was down-regulated in both early and late OA. Inflammatory cytokines including interleukin (IL) 6, IL 8 and IL 18 were up-regulated in early and late OA.Conclusions
The results suggest a dysregulation of wound repair pathways in shoulder OA contributing to the presence of a ''chronic wound’ that progresses irreversibly from early to later stages of OA. Protease inhibitors were downregulated in late OA suggesting uncontrolled proteolytic activity occurring in late OA. These results contribute to the theory that protease inhibitors represent promising therapeutic agents which could limit proteolytic activity that ultimately leads to cartilage destruction. 相似文献67.
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69.
Luis Muniz-Feliciano Jennifer Van Grol Jose-Andres C. Portillo Lloyd Liew Bing Liu Cathleen R. Carlin Vern B. Carruthers Stephen Matthews Carlos S. Subauste 《PLoS pathogens》2013,9(12)
Toxoplasma gondii resides in an intracellular compartment (parasitophorous vacuole) that excludes transmembrane molecules required for endosome - lysosome recruitment. Thus, the parasite survives by avoiding lysosomal degradation. However, autophagy can re-route the parasitophorous vacuole to the lysosomes and cause parasite killing. This raises the possibility that T. gondii may deploy a strategy to prevent autophagic targeting to maintain the non-fusogenic nature of the vacuole. We report that T. gondii activated EGFR in endothelial cells, retinal pigment epithelial cells and microglia. Blockade of EGFR or its downstream molecule, Akt, caused targeting of the parasite by LC3+ structures, vacuole-lysosomal fusion, lysosomal degradation and killing of the parasite that were dependent on the autophagy proteins Atg7 and Beclin 1. Disassembly of GPCR or inhibition of metalloproteinases did not prevent EGFR-Akt activation. T. gondii micronemal proteins (MICs) containing EGF domains (EGF-MICs; MIC3 and MIC6) appeared to promote EGFR activation. Parasites defective in EGF-MICs (MIC1 ko, deficient in MIC1 and secretion of MIC6; MIC3 ko, deficient in MIC3; and MIC1-3 ko, deficient in MIC1, MIC3 and secretion of MIC6) caused impaired EGFR-Akt activation and recombinant EGF-MICs (MIC3 and MIC6) caused EGFR-Akt activation. In cells treated with autophagy stimulators (CD154, rapamycin) EGFR signaling inhibited LC3 accumulation around the parasite. Moreover, increased LC3 accumulation and parasite killing were noted in CD154-activated cells infected with MIC1-3 ko parasites. Finally, recombinant MIC3 and MIC6 inhibited parasite killing triggered by CD154 particularly against MIC1-3 ko parasites. Thus, our findings identified EGFR activation as a strategy used by T. gondii to maintain the non-fusogenic nature of the parasitophorous vacuole and suggest that EGF-MICs have a novel role in affecting signaling in host cells to promote parasite survival. 相似文献
70.
Shawnita Sealy-Jefferson Brenda W. Gillespie Allison E. Aiello Mary N. Haan Lewis B. Morgenstern Lynda D. Lisabeth 《PloS one》2013,8(6)