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31.
A model of the carbohydrate recognition domain CRD, residues 111-245, of
hamster galectin-3 has been made using homology modeling and dynamics
minimization methods. The model is based on the known x-ray structures of
bovine galectin-1 and human galectin-2. The oligosaccharides
NeuNAc-alpha2,3-Gal-beta1,4-Glc and GalNAc-alpha1, 3-
[Fuc-alpha1,2]-Gal-beta1,4-Glc, known to be specific high-affinity ligands
for galectin-3, as well as lactose recognized by all galectins were docked
in the galectin-3 CRD model structure and a minimized binding conformation
found in each case. These studies indicate a putative extended
carbohydrate-binding subsite in the hamster galectin- 3 involving Arg139,
Glu230, and Ser232 for NeuNAc-alpha2,3-; Arg139 and Glu160 for
fucose-alpha1,2-; and Arg139 and Ile141 for GalNAc-alpha1,3- substituents
on the primary galactose. Each of these positions is variable within the
whole galectin family. Two of these residues, Arg139 and Ser232, were
selected for mutagenesis to probe their importance in this newly identified
putative subsite. Residue 139 adopts main-chain dihedral angles
characteristic of an isolated bridge structural feature, while residue 232
is the C-terminal residue of beta- strand-11, and is followed immediately
by an inverse gamma-turn. A systematic series of mutant proteins have been
prepared to represent the residue variation present in the aligned
sequences of galectins-1, - 2, and -3. Minimized docked models were
generated for each mutant in complex with NeuNAc-alpha2,3-Gal-beta1,4-Glc,
GalNAc-alpha1, 3-[Fuc- alpha1,2]-Gal-beta1,4- Glc, and Gal-beta1,4-Glc.
Correlation of the computed protein-carbohydrate interaction energies for
each lectin- oligosaccharide pair with the experimentally determined
binding affinities for fetuin and asialofetuin or the relative potencies of
lactose and sialyllactose in inhibiting binding to asiolofetuin is
consistent with the postulated key importance of Arg139 in recognition of
the extended sialylated ligand.
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32.
Caspase inhibition can extend the survival of cells undergoing apoptosis beyond the point of mitochondrial outer membrane permeabilisation (MOMP), but this does not confer long-term protection because caspase-independent death pathways emerge. Here, we describe a novel mechanism of mitochondrial self-destruction in caspase-inhibited cells, whose hallmark is the degradation of Tim23, the essential pore-forming component of the TIM23 inner membrane translocase. We show that Tim23 degradation occurs in cycling and post-mitotic cells, it is caspase-independent but Bax/Bak dependent, and it follows cytochrome c release. The proteolytic degradation of Tim23 is induced by MOMP and is mitochondrion-autonomous, as it also occurs in isolated mitochondria undergoing permeability transition. Degradation of Tim23 is selective, as expression of several other inner membrane proteins that regulate respiratory chain function is unaffected, and is not autophagic, as it occurs similarly in autophagy-proficient and -deficient (Atg-5 knockout) cells. Depleting Tim23 with siRNA is sufficient to inhibit cell proliferation and prevent long-term survival, while expression of degradation-resistant Tim23-GFP in mitochondria delays caspase-independent cell death. Thus, mitochondrial autodigestion of Tim23 joins the array of processes contributing to caspase-independent cell death. Because mitochondrial biogenesis requires a functional protein-import machinery, preventing Tim23 degradation might, therefore, be essential for repairing damaged mitochondria in chronic degenerative diseases. 相似文献
33.
Java language has been demonstrated to be an effective tool in supporting medical image viewing in Russia. This evaluation was completed by obtaining a maximum of 20 images, depending on the client's computer workstation from one patient using a commercially available computer tomography (CT) scanner. The images were compared against standard CT images that were viewed at the site of capture. There was no appreciable difference. The client side is a lightweight component that provides an intuitive interface for end users. Each image is loaded in its own thread and the user can begin work after the first image has been loaded. This feature is especially useful on slow connection speed, 9.6 Kbps for example. The server side, which is implemented by the Java Servlet Engine works more effective than common gateway interface (CGI) programs do. Advantages of the Java Technology place this program on the next level of application development. This paper presents a unique application of Java in telemedicine. 相似文献
34.
Elisangela F Silva Mariana Orsi ?ngela L Andrade Rosana Z Domingues Breno M Silva Helena RC de Araújo Paulo FP Pimenta Michael S Diamond Eliseu SO Rocha Erna G Kroon Luiz CC Malaquias Luiz FL Coelho 《Journal of nanobiotechnology》2012,10(1):1-5
Background
Dengue is a major public health problem worldwide, especially in the tropical and subtropical regions of the world. Infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing secondary infection with a different serotype progresses to the severe form of the disease, dengue hemorrhagic fever/dengue shock syndrome. Currently, there are no licensed vaccines or antiviral drugs to prevent or treat dengue infections. Biodegradable nanoparticles coated with proteins represent a promising method for in vivo delivery of vaccines.Findings
Here, we used a murine model to evaluate the IgG production after administration of inactivated DENV corresponding to all four serotypes adsorbed to bovine serum albumin nanoparticles. This formulation induced a production of anti-DENV IgG antibodies (p < 0.001). However, plaque reduction neutralization assays with the four DENV serotypes revealed that these antibodies have no neutralizing activity in the dilutions tested.Conclusions
Our results show that while the nanoparticle system induces humoral responses against DENV, further investigation with different DENV antigens will be required to improve immunogenicity, epitope specicity, and functional activity to make this platform a viable option for DENV vaccines. 相似文献35.
Shaun A Tauck Jesse R Olsen Jarrod RC Wilkinson Riley J Wedlake Kathleen C Davis James G Berardinelli 《Reproductive biology and endocrinology : RB&E》2010,8(1):89
Background
The physiological mechanism by which bulls stimulate resumption of ovarian cycling activity in postpartum, anovular, suckled cows after calving may involve the concurrent activation of the hypothalamic-hypophyseal-ovarian (HPO) axis and hypothalamic-hypophyseal-adrenal (HPA) axis. Thus, the objectives of this experiment were to determine if characteristics of temporal patterns of cortisol and luteinizing hormone (LH) in postpartum, anovular, beef cows are influenced by acute exposure to bulls. The null hypotheses were that daily, temporal characteristics of cortisol and LH concentration patterns do not differ between cows exposed acutely to bulls or steers. 相似文献36.
37.
On the origins of esterases 总被引:8,自引:0,他引:8
Comparisons among the primary sequences of five cloned eukaryotic esterases
reveal two distinct lineages, neither bearing any significant overall
sequence similarity to the functionally related serine protease multigene
family. We have not eliminated the possibility that the esterases may have
residual conformational similarities to the serine proteases. However, our
profile analysis and analyses of the predicted conformations of the
esterases reveal little similarity to the serine proteases. Four of the
esterase proteins share 27%-53% overall sequence similarity and evidence of
a catalytic mechanism involving the same Arg- Asp-Ser or His-Asp-Ser charge
relay. We propose that these four esterases, three of them cholinesterases,
form part of a multigene family essentially separate from the serine
proteases.
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