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71.
Auditory aftereffects were evaluated after short adaptation to radial sound source motion with different velocities. Approach
and withdrawal of the sound source were simulated by means of rhythmical noise (from 20 Hz to 20 kHz) impulse sequences with
an arising or diminishing amplitude. They were presented to an anechoic chamber through two loudspeakers placed at 1.1 and
4.5 m from the listener. The adapting stimulus velocities were 0.68, 3.43, 6.92, and 9.97 m/s with an adaptation duration
of 5 s. At all motion velocities, the aftereffect manifested itself in divergence of psychometric functions upon approaching
and withdrawing of adaptors. The direction of function displacements was opposite to that of the adaptor motion. Three parameters
reflecting alteration of perception after motion adaptation were determined and compared with control data: the evaluation
of stationary test stimuli; the velocity of moving test signal at the point of subjective equality (perceptually unmoving
point); and the percentage of responses after averaging over all test signals. These parameters of auditory radial motion
aftereffect similarly changed with the adaptor velocity. They demonstrated a significant effect at slow motion (0.68 and 3.43
m/s) and a small effect at a quick motion (6.92 and 9.97 m/s). 相似文献
72.
Xiuhong Zhai Margarita L. Malakhova Helen M. Pike Linda M. Benson H. Robert Bergen III Istv��n P. Sug��r Lucy Malinina Dinshaw J. Patel Rhoderick E. Brown 《The Journal of biological chemistry》2009,284(20):13620-13628
Glycolipid transfer proteins (GLTPs) are small, soluble proteins that
selectively accelerate the intermembrane transfer of glycolipids. The GLTP
fold is conformationally unique among lipid binding/transfer proteins and
serves as the prototype and founding member of the new GLTP superfamily. In
the present study, changes in human GLTP tryptophan fluorescence, induced by
membrane vesicles containing glycolipid, are shown to reflect glycolipid
binding when vesicle concentrations are low. Characterization of the
glycolipid-induced “signature response,” i.e. ∼40%
decrease in Trp intensity and ∼12-nm blue shift in emission wavelength
maximum, involved various modes of glycolipid presentation, i.e.
microinjection/dilution of lipid-ethanol solutions or phosphatidylcholine
vesicles, prepared by sonication or extrusion and containing embedded
glycolipids. High resolution x-ray structures of apo- and holo-GLTP indicate
that major conformational alterations are not responsible for the
glycolipid-induced GLTP signature response. Instead, glycolipid binding alters
the local environment of Trp-96, which accounts for ∼70% of total emission
intensity of three Trp residues in GLTP and provides a stacking platform that
aids formation of a hydrogen bond network with the ceramide-linked sugar of
the glycolipid headgroup. The changes in Trp signal were used to
quantitatively assess human GLTP binding affinity for various lipids including
glycolipids containing different sugar headgroups and homogenous acyl chains.
The presence of the glycolipid acyl chain and at least one sugar were
essential for achieving a low-to-submicromolar dissociation constant that was
only slightly altered by increased sugar headgroup complexity.Glycolipid transfer protein
(GLTP)4 is a soluble
(∼24-kDa) protein that selectively transfers glycosphingolipids (GSLs)
between membranes. GSLs play key roles in cell recognition, adhesion,
differentiation, proliferation, and programmed death in normal and disease
states
(1–8).
Phylogenetic/evolutionary analyses show GLTP to be highly conserved among
vertebrates
(9–11).
The conformational uniqueness of the GLTP fold when compared with other lipid
binding/transfer proteins
(12–14)
has resulted in GLTP being designated the prototype and founding member of the
GLTP superfamily (15,
16). GLTP employs a novel
two-layer “sandwich motif,” dominated by α-helices and
achieved without intramolecular disulfide bridges, to accommodate glycolipid
within a single lipid binding site and to form a membrane-interaction domain
that differs from other known membrane targeting/translocation domains,
i.e. C1, C2, PH, PX, and FYVE
(9,
13,
17–21).
The glycolipid binding site of GLTP consists of a sugar headgroup recognition
center that anchors the ceramide-linked sugar to the protein surface via
multiple hydrogen bonds and a hydrophobic tunnel that accommodates the
hydrocarbon chains of ceramide. The crystal structures of glycolipid-free GLTP
and of GLTP complexed with a half-dozen glycolipids differing in sugar
headgroup and/or lipid acyl composition reveal the basis for specific
recognition and adaptive accommodation of various GSLs. A conserved, concerted
sequence of events, initiated by anchoring of the GSL headgroup to the sugar
headgroup recognition center, seems to facilitate entry and exit of the lipid
chains in the membrane-associated state
(13). Glycolipid uptake occurs
via a cleft-like gating mechanism involving conformational changes to one
α-helix and two interhelical loops
(12). The selectivity of GLTP
for glycolipids makes this protein a prime candidate for molecular
manipulation of GSL-enriched microdomains in membranes as well as a potential
vehicle for selectively delivering glycolipids to cells. However, the binding
affinity of various glycolipids for GLTP and the time frame of GSL uptake by
GLTP remain unclear. In the present study, these issues are investigated using
fluorescence approaches.GLTP is intrinsically fluorescent by virtue of having 3 Trp and 10 Tyr
residues among its 209 amino acids. All 3 Trp residues reside on or near the
surface of GLTP
(12–14,
17,
22,
23), where they could help
form a membrane-interaction site. Only one, Trp-96, is directly involved in
glycolipid binding
(12–14).
Given the likely roles in membrane interaction and GSL binding, our goal was
to define the relative contributions of the Trp fluorescence changes caused by
membrane interaction versus glycolipid binding. A signature Trp
emission response, indicative of GSL binding by WT-GLTP, has been identified
and characterized using select GLTP point mutants and different modes of
glycolipid presentation, i.e. ethanol injection of pure GSLs and
titration with membrane vesicles (LUVs and SUVs) containing GSLs as minor
components. The signature Trp emission response has been used to
comprehensively assess the glycolipid binding affinity of the novel GLTP fold
for the first time, focusing on the impact of compositional variation of the
sugar headgroup and nonpolar acyl chain moieties of the glycolipid. 相似文献
73.
74.
Chechetkin VR Prokopenko DV Zasedateleva OA Gitelson GI Lomakin ES Livshits MA Malinina L Turygin AY Krylov AS Mirzabekov AD 《Journal of biomolecular structure & dynamics》2003,21(3):425-433
Binding specificity of mutant V55C disulfide bonded dimeric lambda-Cro protein (CroVC) to double-stranded DNA (dsDNA) was studied using generic hexamer oligonucleotide microchip. The curves of dissociation of hybridized DNA in the presence and absence of CroVC were converted into the effective discriminant constants to assess the relevant thermodynamic equilibrium binding constants for dsDNA-protein complexes. Then, tiling of longer oligonucleotides with shorter oligomers was used to search for sequence motifs with the highest binding specificity similarly to sequencing by hybridization. The comparison of the deduced sequences with the known natural operator half-sites demonstrated the principal ability to discern and reconstruct the major parts of 7-mer motifs corresponding to the strongest binding of CroVC subunits. Our results show the applicability of generic microchips to the analysis of binding specificity in the case of multi-subunit DNA-binding proteins. 相似文献
75.
Interaction of gene wellhaarig (we) with genes waved alopecia (wal) and hairless (hr) was studied in mice. The mutant gene we is responsible for the development of a specific waved coat in homozygotes. Homozygous mice carrying mutant gene wal also have a wavy coat, though a partial alopecia develops with time in these animals. In homozygotes for the hr gene, hair loss is observed beginning from the age of ten days. A series of crosses we/we and wal/wal yielded animals with we/+wal/wal and we/we wal/wal genotypes. In mice we/+wal/wal carrying gene we at a single dose, alopecia is accelerated significantly as compared to the single-dose homozygotes +/+wal/wal. In we/we wal/wal mice, alopecia starts earlier than in we/+wal/wal mice; by the age of one month, the double homozygotes are almost hairless except for small body areas covered with a sparse coat. In addition, curliness of the first-generation hair in mice we/we wal/wal is much more expressed than in +/+wal/wal and we/we+/+ mice. The obtained evidence suggests that the we gene is a modifier of the wal gene because the former enhances the effects of the wal gene, which is confirmed by the earlier onset of alopecia and progression of the latter in mice having the we/+wal/wal genotype and especially in we/we wal/wal animals. The we/we hr/+ mice do not differ in coat from we/we+/+ mice; in both cases, the coat is wavy. The coat of double homozygotes we/we hr/hr, is similar to that of we/we+/+ mice until ten days of age, when the signs of alopecia appear. By the age of 21 days, mice we/we hr/hr have lost their coat completely like mice +/+ hr/hr. Hence, the we gene is a modifier of the wal gene though it does not interact with hr gene during the coat formation. 相似文献
76.
17 blood proteins of infants with rough and multiple congenital malformations (CM), prematurely born infants and sick newborns without developmental anomalies were studied electrophoretically in polyacrylamide and starch gels (62422 locus tests). The control included blood samples of healthy newborns from ordinary maternity hospitals (60234 locus tests). The frequency of rare protein variants in all the cases was higher in sick children than in healthy ones. The frequency of rare genes (corrected for electrophoretically "silent" alleles) was 2.16 X 10(-3) in infants with CM and 0.99 X 10(-4) in the control. Examination of parents of 11 congenitally malformed infants with rare protein variants showed that at least in 5 cases such variants were absent in the parents and might be attributed to "fresh" mutations. However, only 3 variants (1 for serum albumin and 2 for red cell esterase) represented rare heterozygotes with codominant expression. This corresponds to the frequency of 0.59 X 10(-3). In the total population of newborns the proportion of infants with CM was 0.02, which means that the population mutation rate is 1.18 X 10(-5) per gene per generation. The data obtained support the conclusion about strong pressure of stabilizing selection against de novo mutations which change electrophoretic mobility of the protein molecule. The reasons for discrepancy between our data and the recent results of Neel and Mohrenweiser (1984) are discussed. 相似文献
77.
Two crystal forms of the self-complementary tetramer GpGpCpC have been obtained by phase diagram technique: P6(2)22/P6(4)22. a = b = 67.7 A, c = 105.6 A and P3(2)12/P3(1)12, a = b = 116.9 A. c = 116.4 A. Both crystals form diffract at least up to 3.2 A. Diffraction patterns of both crystal forms have strongest base-stacking reflections corresponding to the Bragg spacing 3.38 A which is typical for B-DNA. Moreover the self-rotation function of the first crystal form shows regular located two-fold pseudo-axes periodicity of which also indicates that this is B-conformation. The same conclusion can be reached on the basis of the crystal packing of the duplexes in the unit cell. It should be emphasized that this is a new example of B-DNA crystal packing. 相似文献
78.
S E Severin A A Boldyrev S L Stvolinski? M M Bordiukov E N Goncharenko L I Deev I E Malinina Iu B Kudriashov 《Radiobiologiia》1990,30(6):765-768
The influence of carnosine (beta-alanyl-l-histidine) on the survival rate of albino mice subjected to whole-body X-irradiation has been investigated. Carnosine (50-200 mg/kg/day) administered per os during a period of 20 days before irradiation (5.0 Gy) increased the survival rate by 45-65%, whereas the administration of carnosine within 30 days after irradiation (5.5 Gy) produced an insignificant protective effect and caused inhibition of the postirradiation histamine accumulation in the spleen. 相似文献
79.
Hybrids between chum Oncorhynchus keta and pink Oncorhynchus gorbuscha salmon: age,growth and morphology and effects on salmon production
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L. A. Zhivotovsky T. G. Tochilina E. G. Shaikhaev V. P. Pogodin T. V. Malinina A. J. Gharrett 《Journal of fish biology》2016,89(4):2098-2106
Mature hybrids between chum salmon Oncorhynchus keta and pink salmon Oncorhynchus gorbuscha, which were identified by an intermediate colour pattern, were caught at the Kurilsky Hatchery, Iturup Island, Russia. Most of them were female and 3 years old (a partial freshwater year and 2 marine years), which is intermediate between the ages of maturity of the parental species. The hybrids exceed both parental species in the rate of growth, are large in size and robust and might successfully compete for mating in the wild or be chosen for artificial reproduction. The ratio of the scale length over width, R, is oblate (R < 1), whereas scales of the parental species are prolate (R > 1). From scale analyses, the c.v. in body size of hybrid females at the second marine year is twice that of O. keta, which suggests developmental instability in the hybrid. A dynamic model predicted that continuing hybridization at a low rate does not produce a substantial hybrid load due to selection against advanced‐generation hybrids and backcrosses. A high hybridization rate, however, may be an additional risk for genetic management and should be taken into account in programmes of artificial reproduction of Pacific salmon Oncorhynchus spp., although such hybrids might have commercial use in confined production systems. 相似文献
80.
Kozlov AP Druzin MIa Kurzina NP Malinina EP 《Zhurnal vysshe? nervno? deiatelnosti imeni I P Pavlova》2000,50(4):658-666
The effects of microinjections of D1 selective dopaminergic substances into the medial frontal cortex (MFC) on information storage and proactive interference during delayed (the delay in 3 s) and non-delayed choice in Y-maze were studied. Bilateral microinjection of D1 receptor antagonist SCH 23390 (1 nM, 1 microliter) impaired both delayed and non-delayed choice. In contrast, microinjections of D1 receptor agonist SKF 38393 (1 nM) into the MFC significantly improved the delayed performance and did not influence the non-delayed choice. The effects of proactive interference caused by SCH 23390 and SKF 38393 injections were more pronounced in delayed choice condition than in the non-delayed task. Spatial bias in animal behavior was revealed after the SCH 23390 injections: during erroneous choices rats more frequently turned in the same direction as preferred in a rotation test. The results suggest that impairment of delayed performance in Y-maze observed under the blockade of D1-mediated neurotransmission in the MFC occurs due to enhancement of the processes of proactive interference and disinhibition of the spatial set. 相似文献