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233.
The complete mitochondrial DNA sequence of the shark Mustelus manazo: evaluating rooting contradictions to living bony vertebrates 总被引:5,自引:0,他引:5
A remarkable example of a misleading mitochondrial protein tree is
presented, involving ray-finned fishes, coelacanths, lungfishes, and
tetrapods, with sea lampreys as an outgroup. In previous molecular
phylogenetic studies on the origin of tetrapods, ray-finned fishes have
been assumed as an outgroup to the tetrapod/lungfish/coelacanth clade, an
assumption supported by morphological evidence. Standard methods of
molecular phylogenetics applied to the protein-encoding genes of
mitochondria, however, give a bizarre tree in which lamprey groups with
lungfish and, therefore, ray-finned fishes are not the outgroup to a
tetrapod/lungfish/coelacanth clade. All of the dozens of published
phylogenetic methods, including every possible modification to maximum
likelihood known to us (such as inclusion of site heterogeneity and
exclusion of potentially misleading hydrophobic amino acids), fail to place
the ray-finned fishes in a biologically acceptable position. A likely cause
of this failure may be the use of an inappropriate outgroup. Accordingly,
we have determined the complete mitochondrial DNA sequence from the shark,
Mustelus manazo, which we have used as an alternative and more proximal
outgroup than the lamprey. Using sharks as the outgroup, lungfish appear to
be the closest living relative of tetrapods, although the possibility of a
lungfish/coelacanth clade being the sister group of tetrapods cannot be
excluded.
相似文献
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Multispecific antibody formats provide a promising platform for the development of novel therapeutic concepts that could facilitate the generation of safer, more effective pharmaceuticals. However, the production and use of such antibody-based multispecifics is often made complicated by: 1) the instability of the antibody fragments of which they consist, 2) undesired inter-subunit associations, and 3) the need to include recombinant heterodimerization domains that confer distribution-impairing bulk or enhance immunogenicity. In this paper, we describe a broadly-applicable method for the stabilization of human or humanized antibody Fv fragments that entails replacing framework region IV of a Vκ1/VH3-consensus Fv framework with the corresponding germ-line sequence of a λ-type VL chain. We then used this stable Fv framework to generate a novel heterodimeric multispecific antibody format that assembles by cognate VL/VH associations between 2 split variable domains in the core of the complex. This format, termed multispecific antibody-based therapeutics by cognate heterodimerization (MATCH), can be applied to produce homogeneous and highly stable antibody-derived molecules that simultaneously bind 4 distinct antigens. The heterodimeric design of the MATCH format allows efficient in-format screening of binding domain combinations that result in maximal cooperative activity. 相似文献
237.
Subrata Batabyal Sanghoon Kim Weldon Wright Samarendra Mohanty 《Journal of biophotonics》2021,14(1):e202000234
Delivery of therapeutic genes into retina is proving to reverse degeneration and restore vision, however, viral vector-based gene delivery is prone to immunorejection, inflammatory/immune-response and nontargeted. Here, we report nonviral gene delivery and expression of opsin encoding genes in mouse retina in-vitro and in-vivo by use of pulsed femtosecond laser microbeam. In-vitro patch-clamp recording of the opsin-sensitized retinal cells and visually evoked in-vivo electrical recording from laser-transfected eye of mouse with degenerated retina showed functional response. The ultrafast laser-based naked gene delivery showed minimal damage and reliable expression of therapeutic opsin in cell membrane of the selected cells and in targeted retinal region. Laser-based “naked DNA gene therapy” in a spatially targeted manner will pave the way for treatment of inherited retinal diseases. 相似文献
238.
Brahma S. Sharma Louisa Balazs Ai Jin James Chyan-Ji Wang Weldon B. Jolley Roland K. Robins 《Cancer immunology, immunotherapy : CII》1991,33(2):109-114
Summary We have investigated the ability of a novel immunopotentiator, 7-thia-8-oxoguanosine (7T8OG) to increase the efficacy of a weakly immunogenic murine L1210 leukemia vaccine. The vaccine was prepared by irradiating L1210 leukemia cells in a cesium source with a total of 6000-R dose. DBA/2 mice were treated with 150 mg/kg 7T8OG and/or with vaccine consisting of 107 irradiated cells. In combination therapy, mice first received the vaccine and then were injected with 75 mg/kg 7T8OG 2 h and 4 h after vaccination. One week after the last treatment all mice were inoculated with 104 live leukemia cells intraperitoneally. Control, untreated mice (n = 66) injected with 104 live leukemia cells had a mean survival time ± standard error of 10.5±0.2 days. Treating mice (n = 66) with one, two or three doses of 7T8OG administered i.p. 1 week apart did not increase survival (mean survival time = 10.7 days). Mice immunized with one, two or three doses of vaccine had 14.5±1.1, 45.4±6.2 and 68.3±10.6 days mean survival, respectively. 7T8OG-stimulated vaccination increased the survival dramatically. The best survival was noted when the mice were treated with 2× (vaccine + 7T8OG). Immunization of mice (n = 30) with this treatment regimen increased the mean survival to 156±10.0 days. Over 90% of mice that were treated this way had a cumulative survival time greater than 160 days. In contrast, only 12% of the mice immunized twice with the leukemia vaccine alone survived over 160 days. These results suggest a rationale for the use of this immuno-potentiator with various vaccines for a more effective immunization. 相似文献
239.
G Radhakrishna C C Chin F Wold P J Weldon 《Comparative biochemistry and physiology. B, Comparative biochemistry》1989,94(2):375-378
1. The Rathke's gland secretions of loggerhead (Caretta caretta) and Kemp's ridley (Lepidochelys kempi) sea turtles contain 20 and 10 mg of protein/ml, respectively. The proteins of each species were separated by gel filtration into two major fractions, one (35%) in the excluded volume, and one (50%) with a molecular mass of approximately 55 kDA. 2. The 55 kDa fraction from each species' secretions exhibits a single band on SDS-PAGE (Mr approximately equal to 55,000) and a single amino-terminal sequence. 3. The amino acid compositions of the two 55 kDa proteins are similar, and the first 15 residues of their amino terminus are identical. Both proteins contain glucosamine. 4. Analyses of the amino acid and amino sugar composition of the high molecular weight fractions from the two turtle species also indicate similarities; there are distinct differences between them and their 55 kDa proteins. 相似文献
240.
Decomposable graphical Gaussian model determination 总被引:8,自引:0,他引:8