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71.
72.
Altered levels of Salmonella DNA adenine methylase are associated with defects in gene expression, motility, flagellar synthesis, and bile resistance in the pathogenic strain 14028 but not in the laboratory strain LT2 下载免费PDF全文
Comparative genomic analysis has revealed limited strain diversity between Salmonella pathogenic and nonpathogenic isolates. Thus, some of the relative virulence and host-immune response disparities may be credited to differential gene regulation rather than gross differences in genomic content. Here we show that altered levels of Salmonella DNA adenine methylase (Dam) resulted in acute defects in virulence-associated gene expression, motility, flagellin synthesis, and bile resistance in the Salmonella pathogenic strain 14028 but not in avirulent laboratory strain LT2. The defects in motility exhibited by 14028 in response to altered Dam levels was not dependent on the presence of the regulatory protein, RpoS. The transitioning between flagellar types (phase variation) was also differentially regulated in 14028 versus LT2 in response to dam levels, resulting in distinct differences in flagellin expression states. These data suggest that differential gene regulation may contribute to the relative virulence disparities observed between Salmonella serovars that are closely related at the DNA level. 相似文献
73.
Michael J. Mahan Josep Casadesus John R. Roth 《Molecular & general genetics : MGG》1992,232(3):470-478
Summary We describe recJ mutants of Salmonella typhimurium. The recJ gene maps between sufD and serA (min 62) and is transcribed counterclockwise. Unlike recJ mutants of Escherichia coli, recJ strains of S. typhimurium are sensitive to irradiation with UV light. This sensitivity is equivalent to or greater that that displayed by recBCD mutant strains. The residual ability of phage P22 abc (anti-recBCD) mutants to form plaques on recBCD
+ strains is eliminated in recJ hosts. Thus host RecJ function appears to substitute for the anti-RecBCD functions of phage P22 and may serve to limit RecBCD activity. 相似文献
74.
Karen Silence Torsten Dreier Mahan Moshir Peter Ulrichts Sofie ME Gabriels Michael Saunders Harald Wajant Peter Brouckaert Leander Huyghe Tim Van Hauwermeiren Alain Thibault Hans J De Haard 《MABS-AUSTIN》2014,6(2):523-532
Overexpression of CD70 has been documented in a variety of solid and hematological tumors, where it is thought to play a role in tumor proliferation and evasion of immune surveillance. Here, we describe ARGX-110, a defucosylated IgG1 monoclonal antibody (mAb) that selectively targets and neutralizes CD70, the ligand of CD27.
ARGX-110 was generated by immunization of outbred llamas. The antibody was germlined to 95% human identity, and its anti-tumor efficacy was tested in several in vitro assays. ARGX-110 binds CD70 with picomolar affinity. In depletion studies, ARGX-110 lyses tumor cells with greater efficacy than its fucosylated version. In addition, ARGX-110 demonstrates strong complement-dependent cytotoxicity and antibody-dependent cellular phagocytosis activity. ARGX-110 inhibits signaling of CD27, which results in blocking of the activation and proliferation of Tregs. In a Raji xenograft model, administration of the fucosylated version of ARGX-110 resulted in a prolonged survival at doses of 0.1 mg/kg and above. The pharmacokinetics of ARGX-110 was tested in cynomolgus monkeys; the calculated half-life is 12 days.
In conclusion, ARGX-110 is a potent blocking mAb with a dual mode of action against both CD70-bearing tumor cells and CD70-dependent Tregs. This antibody is now in a Phase 1 study in patients with advanced malignancies expressing CD70 (). NCT01813539相似文献
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Coleman PJ Schreier JD Cox CD Fraley ME Garbaccio RM Buser CA Walsh ES Hamilton K Lobell RB Rickert K Tao W Diehl RE South VJ Davide JP Kohl NE Yan Y Kuo L Prueksaritanont T Li C Mahan EA Fernandez-Metzler C Salata JJ Hartman GD 《Bioorganic & medicinal chemistry letters》2007,17(19):5390-5395
3,5-diaryl-4,5-dihydropyrazoles were discovered to be potent KSP inhibitors with excellent in vivo potency. These enzyme inhibitors possess desirable physical properties that can be readily modified by incorporation of a weakly basic amine. Careful adjustment of amine basicity was essential for preserving cellular potency in a multidrug resistant cell line while maintaining good aqueous solubility. 相似文献
78.
Phylogenetic relationships within the Alcidae (Charadriiformes: Aves) inferred from total molecular evidence 总被引:3,自引:1,他引:3
The Alcidae is a unique assemblage of Northern Hemisphere seabirds that
forage by "flying" underwater. Despite obvious affinities among the
species, their evolutionary relationships are unclear. We analyzed
nucleotide sequences of 1,045 base pairs of the mitochondrial cytochrome b
gene and allelic profiles for 37 allozyme loci in all 22 extant species.
Trees were constructed on independent and combined data sets using maximum
parsimony and distance methods that correct for superimposed changes.
Alternative methods of analysis produced only minor differences in
relationships that were supported strongly by bootstrapping or standard
error tests. Combining sequence and allozyme data into a single analysis
provided the greatest number of relationships receiving strong support.
Addition of published morphological and ecological data did not improve
support for any additional relationship. All analyses grouped species into
six distinct lineages: (1) the dovekie (Alle alle) and auks, (2)
guillemots, (3) brachyramphine murrelets, (4) synthliboramphine murrelets,
(5) true auklets, and (6) the rhinoceros auklet (Cerorhinca monocerata) and
puffins. The two murres (genus Uria) were sister taxa, and the black
guillemot (Cepphus grylle) was basal to the other guillemots. The Asian
subspecies of the marbled murrelet (Brachyramphus marmoratus perdix) was
the most divergent brachyramphine murrelet, and two distinct lineages
occurred within the synthliboramphine murrelets. Cassin's auklet
(Ptychoramphus aleuticus) and the rhinoceros auklet were basal to the other
auklets and puffins, respectively, and the Atlantic (Fratercula arctica)
and horned (Fratercula corniculata) puffins were sister taxa. Several
relationships among tribes, among the dovekie and auks, and among the
auklets could not be resolved but resembled "star" phylogenies indicative
of adaptive radiations at different depths within the trees.
相似文献
79.
Growth of bacteriophage P22 erf is known to require host RecA recombination function. We show that the RecA function is necessary but not sufficient to restore the plaque-forming ability of phage P22 erf; such mutant phage also requires host RecJ function. The residual efficiency of plaquing of P22 erf in a recJ background (0.03%) is completely abolished in recJ recB hosts (< 0.001%), suggesting that the RecBCD nuclease can provide an alternative function allowing phage growth. One tentative explanation is that circularization of P22 erf DNA mostly proceeds through the RecF pathway of recombination; however, less efficient circularization via the RecBCD pathway may also occur. In a recJ background, lysates obtained upon induction of an erf prophage show reduced yield (10%), suggesting that growth of P22 erf may require host RecJ in a step(s) other than circularization of phage DNA. 相似文献