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Rogers AR; Fraley AE; Bamshad MJ; Watkins WS; Jorde LB 《Molecular biology and evolution》1996,13(7):895-902
Mismatch distributions are histograms showing the pattern of nucleotide (or
restriction) site differences between pairs of individuals in a sample.
They can be used to test hypotheses about the history of population size
and subdivision (if selective neutrality is assumed) or about selection (if
a constant population size is assumed). Previous work has assumed that
mutations never strike the same site twice, an assumption that is called
the model of infinite sites. Fortunately, the results are surprisingly
robust even when this assumption is violated. We show here that (1)
confidence regions inferred using the infinite- sites model differ little
from those inferred using a model of finite sites with uniform
site-specific mutation rates, and (2) even when site- specific mutation
rates follow a gamma distribution, confidence regions are little changed
until the gamma shape parameter falls well below its plausible range, to
roughly 0.01. In addition, we evaluate and reject the proposition that
mismatch waves are produced by pooling data from several subdivisions of a
structured population.
相似文献
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Cultures of Achlya sp., Phytophthora cinnamomi, Saprolegnia diclina, S. ferax, and S. parasitica, treated with 6-carboxyfluorescein diacetate solution, accumulate 6-carboxyfluorescein in a reticulate system of fine tubules. The network shows longitudinal polarity within the hyphae, tubules being finest toward the hyphal tips. In more mature subapical regions the network is connected with large vacuoles that also accumulate 6-carboxyfluorescein. A morphologically similar system has also been identified in freeze-substituted hyphae of S. ferax. The network is considered to be vacuolar, but differs from the tubular vacuole system of true fungi in that tubules are less motile, more frequently branched, and do not alternate with clusters of spherical vacuoles. The appearance of the network resembles patterns of calcium-sensitive dye staining and it is suggested that the vacuolar reticulum in the tip region of oomycete hyphae may act as a Ca2+ sink. The tubular reticulum in oomycetes is very fragile and can be shown with 6-carboxyfluorescein in only those hyphal tips with a motility and organelle distribution characteristic of growing hyphae with normal morphology. Diverse abnormal hyphae show a range of other fluorochrome localizations. These include large irregular compartments filled with fluorochrome, and fluorescent cytoplasm with organelles and vacuoles standing out in negative contrast. These localizations in abnormal hyphae are correlated with other structural changes indicative of damage. Special care is required in experiments with oomycetes to avoid such artefacts of localization. Copyright 1997 Academic Press. Copyright 1997 Academic Press 相似文献
44.
A reassessment of decreased amino acid accumulation by ehrlich ascites tumor cells in the presence of metabolic inhibitors 总被引:2,自引:0,他引:2 下载免费PDF全文
This study was undertaken to examine the mechanism by which metabolic inhibition reduces amino acid active transport in ehrlich ascites tumor cells. At 37 degrees C the metabolic inhibitor combination 0.1 mM 2,4-dinitrophenol (DNP) + 10 mM 2- deoxy-D-glucose (DOG) reduced the cell ATP concentration to 0.10- 0.15 mM in less than 5 min. This inhibition was associated with a 20.6 percent +/- 6.4 percent (SD) decrease in the initial influx of α-aminoisobutyric acid (AIB), and a two- to fourfold increase in the unidirectional efflux. These effects could be dissociated from changes in cell Na(+) or K(+) concentrations. Cells incubated to the steady state in 1.0-1.5 mM AIB showed an increased steady-state flux in the presence of DNP + DOG. Steady- state fluxes were consistent with trans-inhibition of AIB influx and trans-stimulation of efflux in control cells, but trans- stimulation of both fluxes in inhibited cells. In spite of the reduction of the cell ATP concentration to less than 0.15 mM and greatly reduced transmembrane concentration gradients of Na(+) and K(+), cells incubated to the steady state in the presence of the inhibitors still established an AIB distribution ration 13.8 +/- 2.6. The results are interpreted to indicate that a component of the reduction of AIB transport produced by metabolic inhibition is attributable to other actions in addition to the reduction of cation concentration gradients. Reduction of cell ATP alone is not responsible for the effects of metabolic inhibition, and both the transmembrane voltage and direct coupling to substrate oxidation via plasma-membrane-bound enzymes must be considered as possible energy sources for amino acid active transport. 相似文献
45.
Association of mouse actin-binding protein 1 (mAbp1/SH3P7), an Src kinase target, with dynamic regions of the cortical actin cytoskeleton in response to Rac1 activation 下载免费PDF全文
Yeast Abp1p is a cortical actin cytoskeleton protein implicated in cytoskeletal regulation, endocytosis, and cAMP-signaling. We have identified a gene encoding a mouse homologue of Abp1p, and it is identical to SH3P7, a protein shown recently to be a target of Src tyrosine kinases. Yeast and mouse Abp1p display the same domain structure including an N-terminal actin-depolymerizing factor homology domain and a C-terminal Src homology 3 domain. Using two independent actin-binding domains, mAbp1 binds to actin filaments with a 1:5 saturation stoichiometry. In stationary cells, mAbp1 colocalizes with cortical F-actin in fibroblast protrusions that represent sites of cellular growth. mAbp1 appears at the actin-rich leading edge of migrating cells. Growth factors cause mAbp1 to rapidly accumulate in lamellipodia. This response can be mimicked by expression of dominant-positive Rac1. mAbp1 recruitment appears to be dependent on de novo actin polymerization and occurs specifically at sites enriched for the Arp2/3 complex. mAbp1 is a newly identified cytoskeletal protein in mice and may serve as a signal-responsive link between the dynamic cortical actin cytoskeleton and regions of membrane dynamics. 相似文献
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Paulo Breinis Flavio Geraldes Alves Camila AE Alves Rafael G Cintra Débora Almeida Priscila C Passarelli Camila Domingues Talita Gerbim Régia Gasparetto Luiz Carlos de Abreu Vitor E Valenti Adriana Gonçalves de Oliveira Carlos Bandeira de Mello Monteiro Rubens Wajnzstejn 《BMC neurology》2014,14(1):1-4
Background
The Mulvihill-Smith Syndrome was first recognized in 1975. After the recognition of the Mulvihill-Smith Syndrome, ten cases have been described.Case presentation
This article describes the eleventh case of this syndrome in a male patient, 24 years-old with short stature and microcephaly with mild cognitive impairment, deafness and allergic conjunctivitis. The patient was hospitalized several times for repeated infections, and the presence of multiple melanocytic nevi on his skin was noticed.Conclusions
Based on the entire set of signs and symptoms presented in our study, it was diagnosed the patient with Mulvihill-Smith Syndrome. 相似文献48.
Philipp Diebolder Armin Keller Stephanie Haase Anne Schlegelmilch Jonathan D Kiefer Tamana Karimi Tobias Weber Gerhard Moldenhauer Roland Kehm Anna M Eis-Hübinger Dirk J?ger Philippe A Federspil Christel Herold-Mende Gerhard Dyckhoff Roland E Kontermann Michaela AE Arndt Jürgen Krauss 《MABS-AUSTIN》2014,6(1):130-142
The development of efficient strategies for generating fully human monoclonal antibodies with unique functional properties that are exploitable for tailored therapeutic interventions remains a major challenge in the antibody technology field. Here, we present a methodology for recovering such antibodies from antigen-encountered human B cell repertoires. As the source for variable antibody genes, we cloned immunoglobulin G (IgG)-derived B cell repertoires from lymph nodes of 20 individuals undergoing surgery for head and neck cancer. Sequence analysis of unselected “LYmph Node Derived Antibody Libraries” (LYNDAL) revealed a naturally occurring distribution pattern of rearranged antibody sequences, representing all known variable gene families and most functional germline sequences. To demonstrate the feasibility for selecting antibodies with therapeutic potential from these repertoires, seven LYNDAL from donors with high serum titers against herpes simplex virus (HSV) were panned on recombinant glycoprotein B of HSV-1. Screening for specific binders delivered 34 single-chain variable fragments (scFvs) with unique sequences. Sequence analysis revealed extensive somatic hypermutation of enriched clones as a result of affinity maturation. Binding of scFvs to common glycoprotein B variants from HSV-1 and HSV-2 strains was highly specific, and the majority of analyzed antibody fragments bound to the target antigen with nanomolar affinity. From eight scFvs with HSV-neutralizing capacity in vitro, the most potent antibody neutralized 50% HSV-2 at 4.5 nM as a dimeric (scFv)2. We anticipate our approach to be useful for recovering fully human antibodies with therapeutic potential. 相似文献
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Roosa AE Laitinen Suvi Broholm Victor A Albert Teemu H Teeri Paula Elomaa 《BMC plant biology》2006,6(1):11-18