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51.
Eswaran J Lee WH Debreczeni JE Filippakopoulos P Turnbull A Fedorov O Deacon SW Peterson JR Knapp S 《Structure (London, England : 1993)》2007,15(2):201-213
p21-activated kinases have been classified into two groups based on their domain architecture. Group II PAKs (PAK4-6) regulate a wide variety of cellular functions, and PAK deregulation has been linked to tumor development. Structural comparison of five high-resolution structures comprising all active, monophosphorylated group II catalytic domains revealed a surprising degree of domain plasticity, including a number of catalytically productive and nonproductive conformers. Rearrangements of helix alphaC, a key regulatory element of kinase function, resulted in an additional helical turn at the alphaC N terminus and a distortion of its C terminus, a movement hitherto unseen in protein kinases. The observed structural changes led to the formation of interactions between conserved residues that structurally link the glycine-rich loop, alphaC, and the activation segment and firmly anchor alphaC in an active conformation. Inhibitor screening identified six potent PAK inhibitors from which a tri-substituted purine inhibitor was cocrystallized with PAK4 and PAK5. 相似文献
52.
Fedorov GS Arokina NK 《Rossi?skii fiziologicheski? zhurnal imeni I.M. Sechenova / Rossi?skaia akademiia nauk》2007,93(10):1171-1180
In rats, data on influence of i. v. administration of calcium chloride on the level of [Ca2+] in the blood and on process of oppression ofthermoregulatory and respiratory functions in rats in hypothermia. 0.18 or 0.135 mmol Ca2+ on the 3rd minute from beginning of the administration increased [Ca2+] in the blood from 1.01 +/- 0.03 to 2.56 +/- 0.08 mM (or 2.27 +/- 0.06 mM). Then [Ca2+] was reduced gradually, in 20 minutes from administration, solution of CaCh [Ca2+] exceeded the initial level by 20-30 %. The increase of concentration of ionized calcium in the rat blood strengthened the cold oppression of breathing and cold shivering as compared with the control (administration of physiological solution). Arrest of breathing in rats after administration of CaCl2 solution occurred at higher rectal temperatures (21 +/- 0.03 degrees C) as compared with control experiments (18 +/- 0.4 degrees C), p < 0.05. It is suggested that increase of [Ca2+] in the blood strengthens effects of cold in the form of oppression of thermoregulatory and respiratory functions. 相似文献
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L. V. Kapitonova S. M. Smirenskii D. S. Selivanova V. V. Fedorov N. A. Formozov 《Biology Bulletin》2011,38(9):912-926
The history of ranges of the great tit (Parus major) and Japanese tit (P. minor) in the Amur River basin is described on the basis of original data collected between 1970 and 2010 and published data. The
main factor accounting for the expansion of the great and Japanese tits to the Amur basin and neighboring territories in the
19th to 21st centuries is economic activity, primarily agriculture and timber harvesting. The approximate range boundaries
and the sympatry zone of these two species have been determined for the second half of the 19th century; the beginning, middle,
and third quarter of the 20th century; and the turn of the 21st century. Three different ecological channels consecutively
played the main role in the eastward expansion of the great tit: the Amur River valley (from the mid-19th to the early 20th
century), the Trans-Siberian Railroad (since the early 20th century), and the Baikal-Amur Railroad (since the 1970s). It is
shown that the concept concerning the finding of great tits in Udskii Ostrog by Middendorff’s expedition is erroneous: according
to dates on the labels, the corresponding two specimens were in fact collected in a different geographic locality. It has
been found that Komsomolsk-on-Amur is a new locality jointly inhabited by both species, independent of the main zone of their
sympatry. It has appeared very recently, at the turn of the 21st century. 相似文献
56.
E. V. Moiseeva N. R. Kuznetsova E. V. Svirshchevskaya N. V. Bovin N. S. Sitnikov A. S. Shavyrin I. P. Beletskaya S. Combes A. Yu. Fedorov E. L. Vodovozova 《Biochemistry (Moscow) Supplemental Series B: Biomedical Chemistry》2011,5(3):276-283
The antimitotic agent combretastatin A-4 (CA-4) has been recently proposed as an antivascular agent for anticancer therapy.
In order to reduce systemic toxicity by means of administration in liposome formulations, new lipophilic prodrugs, oleic derivatives
of CA-4 and its 4-arylcoumarin analogue (CA4-Ole and ArC-Ole, respectively), have been synthesized in this study. Liposomes
with mean diameter of 100 nm prepared on the basis of egg phosphatidylcholine and baker’s yeast phosphatidylinositol quantitatively
included up to 15 mol% of CA4-Ole, or 7 mol% of ArC-Ole. To achieve targeting to neovascular endothelium prodrug bearing liposomes
decorated with the tetrasaccharide selectin ligand Sialyl Lewis X (SiaLeX) have been also prepared. The antitumor activity
was studied in vivo using the model of slow-growing mouse breast cancer. Under the dose used (22 mg/kg) and the administration
protocol (four injections, one per a week, starting from the appearance of palpable tumors) cytostatic CA-4 did not reveal
any anticancer effect; moreover, it even stimulated tumor growth. The liposome formulations of CA4-Ole did not demonstrate
such stimulation. However, to achieve a pronounced antitumor effect, the number of injections of liposomes should be apparently
increased. The cytotoxic activity of a novel antimitotic agent ArC was one order of magnitude lower in the human breast carcinoma
cell culture in vitro. Nevertheless, in vivo in the mouse model of breast cancer the antitumor effect of this compound corresponded
to the double equivalent dose of CA-4. The results demonstrate perspectives of SiaLeX-liposomes loaded with ArC-Ole: the preparation partially inhibited tumor growth already after the second injection. Thus,
subsequent optimization of doses and regimens of administration both for ArC and liposomal ArC-Ole formulations are needed. 相似文献
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Angela Schoolmeesters Teresa Eklund Devin Leake Annaleen Vermeulen Queta Smith Shelley Force Aldred Yuriy Fedorov 《PloS one》2009,4(5)