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Biomedical subjects

C Qu

Publications and source records attributed to C Qu.

18 recordsLinked to original sources

Inhibition of the calcium- and voltage-dependent big conductance potassium channel ameliorates cisplatin-induced apoptosis in spiral ligament fibrocytes of the cochlea.

The role of calcium- and voltage-dependent big conductance potassium channels in regulating apoptosis was investigated in cultured type I spiral ligament fibrocytes. Incubation of type I spiral ligament fibrocytes derived from gerbil cochlea with cisplatin induced dose- and time-dependent apoptosis as demonstrated by annexin V conjugated to fluorescein isothiocyanate/prodidium iodide assays. The average voltage activation threshold of whole cell current was sharply shifted to -40 mV in the cisplatin-treated cells as compared with a value of 40 mV in control cells. The average whole-cell current of cisplatin-treated cells induced by a depolarization voltage step from -80 to -10 mV was increased significantly to 1.2+/-0.4 nA as compared with 0.08+/-0.1 nA in control cells. Coincubation with tetraethylammonium and cisplatin retained the whole cell current in the normal range (0.12+/-0.2 nA). The increment of cisplatin-induced whole-cell current was inhibited (97+/-5%) by a specific calcium- and voltage-dependent big conductance potassium channel blocker iberiotoxin. Consistent with this, co-incubation with tetraethylammonium significantly attenuated cisplatin-induced apoptosis in type I spiral ligament fibrocytes by more than 50%. We conclude that the activation of BK channels is an early event associated with cisplatin-induced apoptosis in type I spiral ligament fibrocytes. These findings also point to the calcium- and voltage-dependent big conductance potassium channels as a potential pharmacological target for manipulating cisplatin ototoxicity.

Animals↗

Design, X-ray crystallography, molecular modelling and thermal stability studies of mutant enzymes at site 172 of 3-isopropylmalate dehydrogenase from Thermus thermophilus.

The relationship between the structure and the thermostability of the 3-isopropylmalate dehydrogenase from Thermus thermophilus was studied by site-directed mutation of a single Ala residue located at the domain interface. The crystal structures of three mutant enzymes, replacing Ala172 with Gly, Val and Phe, were successfully determined at 2.3, 2.2 and 2.5 A resolution, respectively. Substitution of Ala172 by relatively 'short' residues (Gly, Val or Ile) enlarges or narrows the cavity in the vicinity of the C(beta) atom of Ala172 and the thermostablity of the enzyme shows a good correlation with the hydrophobicity of the substituted residues. Substitution of Ala172 by the 'longer' residues Leu or Phe causes a rearrangement of the domain structure, which leads to a higher thermostability of the enzymes than that expected from the hydrophobicity of the substituted residues. Mutation of Ala172 to negatively charged residues gave an unexpected result: the melting temperature of the Asp mutant enzyme was reduced by 2.7 K while that of the Glu mutant increased by 1.8 K. Molecular-modelling studies indicated that the glutamate side chain was sufficiently long that it did not act as a buried charge as did the aspartate, but instead protruded to the outside of the hydrophobic cavity and contributed to the stability of the enzyme by enhancing the packing of the local side chains and forming an extra salt bridge with the side chain of Lys175.

3-Isopropylmalate Dehydrogenase↗

3D domain swapping modulates the stability of members of an icosahedral virus group.

BACKGROUND: Rice yellow mottle virus (RYMV) is a major pathogen that dramatically reduces rice production in many African countries. RYMV belongs to the genus sobemovirus, one group of plant viruses with icosahedral capsids and single-stranded, positive-sense RNA genomes. RESULTS: The structure of RYMV was determined and refined to 2.8 A resolution by X-ray crystallography. The capsid contains 180 copies of the coat protein subunit arranged with T = 3 icosahedral symmetry. Each subunit adopts a jelly-roll beta sandwich fold. The RYMV capsid structure is similar to those of other sobemoviruses. When compared with these viruses, however, the betaA arm of the RYMV C subunit, which is a molecular switch that regulates quasi-equivalent subunit interactions, is swapped with the 2-fold-related betaA arm to a similar, noncovalent bonding environment. This exchange of identical structural elements across a symmetry axis is categorized as 3D domain swapping and produces long-range interactions throughout the icosahedral surface lattice. Biochemical analysis supports the notion that 3D domain swapping increases the stability of RYMV. CONCLUSIONS: The quasi-equivalent interactions between the RYMV proteins are regulated by the N-terminal ordered residues of the betaA arm, which functions as a molecular switch. Comparative analysis suggests that this molecular switch can also modulate the stability of the viral capsids.

Amino Acid Sequence↗

Synthesis of highly potent second-generation taxoids through effective kinetic resolution coupling of racemic beta-lactams with baccatins.

A series of highly potent second-generation taxoids bearing a 2-methylprop-1-enyl or a 2-methylpropyl group at C-3' with modifications at the C-2, C-10, and C-14 positions was synthesized through the coupling of racemic cis-beta-lactams with properly protected/modified baccatin and 14-OH-baccatin. A high level of kinetic resolution was observed for all cases examined. The observed highly efficient enantiomer differentiation is ascribed to the markedly different chiral environment between the (+)- and (-)-beta-lactams in their approach to the chiral framework of the enantiopure lithium alkoxide of a baccatin in the ring-opening coupling process. It was also observed that substantially higher selectivity was achieved when 14-OH-baccatin-1,14-carbonate was used. Analysis of the transition state models revealed that the repulsive interactions between the 3-TIPS group of a (-)-beta-lactam with 1, 14-carbonate group of the baccatin substantially increases the asymmetric bias in the kinetic resolution process, favoring the reaction of a (+)-beta-lactam, which leads to the observed excellent selectivity.

Alkaloids↗

[Cataract extraction with rotated-chipping phacoemulsification in the capsule].

OBJECTIVE: To observe the clinical effects of rotated-chipping phacoemulsification in the capsule. METHODS: The operation of continuous circular capsulectomy, nuclear hydrodissection, cataract extraction with rotated-chipping phacoemulsification in capsule and intraocular lens implantation was performed on 215 eyes. RESULTS: Rotated-chipping technique was successfully completed in 215 eyes. In the operation 2 to 4 circles were rotated with the ultrasonic energy 19.3% for 12 seconds on average. The rate of corneal endothelium loss was 7.5%. CONCLUSION: The technique of rotated-chipping phacoemulsification in capsule is safe and rapid which can be used for cataracts with nuclei of various degrees in sclerosis.

Aged↗

[Acoustic analysis and characteristics of vocal range in Beijing Opera actors].

OBJECTIVE: To get the objective acoustic parameters of the voice of Beijing Opera actors and set a foundation for the training and protection of the special professional voice. METHODS: Seventy-three (age 16-57 years) professional actors and students were asked to produce sustained comfortable vowels /a/ and /i/, and to sing two pieces of songs which were in the category of Xipi and Erhuang respectively. Dr. Speech for windows version 3.0 was used to get the acoustic parameters of the vowels and the songs. RESULTS: F0 of the vowels /a/ and /i/ of different Hangdangs were Chou (272.6 +/- 42.0) Hz (mean +/- s), (304.2 +/- 22.1) Hz; Xiaosheng (499.3 +/- 34.0) Hz, (485.4 +/- 18.7) Hz; Laosheng (335.6 +/- 60.0) Hz, (317.9 +/- 45.1) Hz; Hualian (319.0 +/- 61.3) Hz, (340.1 +/- 68.8) Hz; Laodan (427.6 +/- 47.2) Hz, (437.7 +/- 45.8) Hz; Huadan (535.8 +/- 48.8) Hz, (561.6 +/- 29.2) Hz; Qingyi (548.0 +/- 69.5) Hz, (543.5 +/- 79.3) Hz; these and other acoustic parameters of vowels such as Jitter, Shimmer and NNE were all within the normal range given by the software. The vocal range of Beijing Opera actors was from 1.7 to 2.8 oct, and most of the highest and the lowest pitches were higher than that of tenor or soprano. CONCLUSIONS: These findings may help to provide insight regarding the acoustic characteristics of the voice of Beijing Opera actors.

Adolescent↗

[Prevalence of premenstrual syndrome in reproductive women and its influential factors].

OBJECTIVE: To investigate the prevalence of premenstrual syndrome and its influential factors in reproductive women. METHOD: A questionnaire was used in 454 reproductive women aged 15-49 in Beijing. RESULTS: The prevalence of premenstrual syndrome in these women was 30.4%, among which 61.6% was mild, 34.1% moderate, and 4.3% severe. The order of frequency of the symptoms occurring in premenstrual syndrome was irritation, depression, anxiety, diarrhea, lack of concentration and hypersomnia. Women with higher cultural level, greater stress in life (work or study), dysmenorrhea, dislike menstruation and those with depression symptom had a higher incidence than those with lower cultural level, no stress in life, no dysmenorrhea, no dislike toward menstruation and no depression symptom (P < 0.05). CONCLUSIONS: Premenstrual syndrome is a common disease in reproductive women. Clinical doctors should pay attention and adopt comprehensive measures in order to reduce its incidence and improve the quality of life especially for women with high risk factors.

Adolescent↗

[Effect of rotundine on gastric acid and pepsin activity in rats].

A test was made on the effect of rotundine on the secretion of gastric acid and pepsin activity in rats. Compared with the control group, rotundine(> or = 17.1 mg/kg) inhibited gastric acid and decreased secretion of gastric juice(P < 0.01), but had no influence on pepsin activity. There was a negative relationship between total acidity and pH of gastric juice (r = -0.9818).

Animals↗

Effect of polar side chains at position 172 on thermal stability of 3-isopropylmalate dehydrogenase from Thermus thermophilus.

To understand the role of the amino acid residue at position 172 in the conformational stability, four mutant enzymes of Thermus thermophilus 3-isopropylmalate dehydrogenase in which Ala172 was replaced with Asp, Glu, Asn, and Gln were prepared by site-directed mutagenesis. Three mutants were more stable than the wild-type enzyme. No significant change in catalytic properties was found in the mutant enzymes. The molecular modeling studies suggested that the enhanced thermostability of the mutant enzymes resulted from the formation of extra electrostatic interactions and/or improvement of hydrophobic packing of the interior core.

3-Isopropylmalate Dehydrogenase↗

A mutation at the interface between domains causes rearrangement of domains in 3-isopropylmalate dehydrogenase.

The structure of a thermostable Ala172Leu mutant, designated A172L, of 3-isopropylmalate dehydrogenase from Thermus thermophilus was determined. The crystal belongs to space group P2(1), with cell parameters a = 55.5 A, b = 88.1 A, c = 72.0 A and beta = 100.9 degrees. There is one dimer in each asymmetric unit. The final R factor is 17.8% with 69 water molecules at 2.35 A resolution. The mutation is located at the interface between domains and the C alpha trace of the mutant structure deviates from that of the native structure by as much as 1.7 A, while the structure of each domain barely changes. The mutant enzyme has a more closed conformation compared with the wild-type enzyme as a result of the replacement of Ala with Leu at residue 172. These structural variations were found independent of the crystal packing, because the structure of wild type was the same in crystals obtained in different precipitants. The hinge regions for the movement of domains are located around the active cleft of the enzyme, an observation that implies that the mobility of domains around the hinge is indispensable for the activity of the enzyme. The larger side chain at the mutated site contributed to the thermostability of the mutant protein by enhancing the local packing of side chains, and also by shifting the backbone of the opposing domain.

3-Isopropylmalate Dehydrogenase↗

[Studies on bone density in healthy girls during their period of growth spurt].

Bone mass in 69 healthy girls in their period of growth spurt was measured twice, with an interval of one year, by dual energy X-ray bone densitometer to study the relationship between changes in bone density and the speed of height growth, development of secondary sex characteristics and nutritional status. Results showed that bone density in the different sites in the period of growth spurt increased significantly with their age, but with difference in the magnitude of its increase and in the time. Their nutritional status (overweight or underweight) correlated closely with sex development and increase in bone density. It suggests that it is necessary to strengthen nutrient intake during their puberty for preventing from osteoporosis. In addition, early puberty is an important period for the increase in female bone density, as a result of comparison of bone mass between prepuberty girls and young women. The results in this study can provide reference for further studies on bone mass in girls during their puberty.

Bone Density↗

[Occurrence of depression symptoms and their influence factors in perimenopausal women].

OBJECTIVE: To investigate the prevalence of depression symptoms and their influence factors in perimenopausal women. METHODS: Self-rating depression scale and general condition questionaire were used in 419 perimenopausal women aged 45-55 in Beijing city. RESULTS: The prevalence of depression symptoms in these women was 46.1%, among which 69.9% was mild and 30.1% moderate or severe. The occurrence of depression symptoms in worker group was higher than cadres or skilled person groups (P < 0.01). The incidence of depression symptoms in women with systemic diseases was higher than those without (P < 0.001). Women with decreased libido and dissatisfaction with their husbands, family income and living conditions had a higher incidence than those without (P < 0.05). CONCLUSIONS: The prevalence of depression symptoms in perimenopausal women was considerably high. Clinical doctors should pay attention to psychological problems especially for women with high risks during medical treatment.

Adult↗

Phylogenetic evidence for the transfer of Pseudomonas cocovenenans (van Damme et al. 1960) to the genus Burkholderia as Burkholderia cocovenenans (van Damme et al. 1960) comb. nov.

Pseudomonas cocovenenans, the producer of bongkrekic acid and toxoflavin, has been described previously by us (N.-X. Zhao, M.-S. Ma, Y.-P. Zhang, and D.-C. Xu, Int. J. Syst. Bacteriol. 40:452-455, 1990) in terms of more than 180 phenotypic traits, G+C content, and DNA relatedness. The bacterium conformed to section II of the genus Pseudomonas. Here, its partial 16S rRNA gene sequence was compared with those of Burkholderia spp., and the results verified that P. cocovenenans is a Burkholderia species. On the basis of the phenotype and genetic characteristics, P. cocovenenans is transferred to the genus Burkholderia as Burkholderia cocovenenans comb. nov.

Amino Acids↗

[The effects of antitumor agents of croton alkaloids and cisplatin on human red blood cell membranes].

The effects of antitumor drugs of croton alkaloids (CA) extracted from croton, and cisplatin on the structure of human erythrocyte membrane and bovine serum albumin (BSA) were studied with the techniques of circular dichroism, fluorescence spectroscopy and ultraviolet absorption. From measuring circular dichroism between 200-240nm, it was found that the alpha helix of membrane and BSA increased after CA addition. Cisplatin was also found effective in altering membrane alpha helical content. BSA showed a loss of fluorescence intensity and a blue-shift of emission peak after CA addition. The florescence quenching and peak shift may reflect the movement of tryptophan to a more nonpolar environment (the hydrophobic portions of proteins). This is consistent with the increase in helicity of BSA in the presence of CA. From measuring fluorescence polarization of membrane, it was found that membrane fluidity decreased in the presence of CA, but did not change in the presence of cisplatin. The results indicate that both CA and cisplatin lead to alterations in the secondary structure of membrane protein. The conformation change in membrane protein may account for the pharmocological effect of CA and cisplatin.

Alkaloids↗

[Intelligence study on 1758 deaf children in China].

In order to determine the character of mental development and the influencing factors of childhood deafness in China the revised H-NTLA was applied to 1758 deaf children within the age range of 3 to 17 years. Compared with 1788 normal hearing children, the results showed that (1) the deaf children were about 20 points lower in IQ than those with normal hearing; (2) the average retardation was found to be about 6 months in 3-5 years old age, the difference became significant from 6 years old, the average retardation was found to be 36 months during 13 years old; (3) the scores were the same as those of the normal hearing children for block patterns, paper folding and puzzle blocks in 3-9 age groups; for visual attention span and spatial reasoning in 16-17 age groups. The scores were retarded significantly on picture association, picture analogies, memory for color and digits; (4) the influencing factors were found with stepwise regression model to be audiphone wearing, education fee and the beginning age of education.

Adolescent↗

Effects of liuwei dihuang wan [symbol: see text:bd and some other TCM drugs on bone biomechanics and serum 25 (OH)D3 content in rats.

After a relatively long-term injection of hydrocortisone into rats, the strength of bone (anti-stress capacity) reduced evidently, while the rigidity (anti-deformity capacity) increased markedly (ie, bone fragility elevated). At the same time, the content of serum 25(OH)D3 decreased remarkably. After oral administration of Liuwei Dihuang Wan ([see symbol: see text]), anti-stress capability of bone increased evidently and its anti-deformity capability returned to normal; however, there was no elevation of serum 25(OH)D3 content. The effect of Longmu Zhuanggu Chongji ([see symbol: see text]) or Jisheng Shenqi Wan (see symbol: see text]) was lower than that of Liuwei Dihuang Wan. The experiments suggests that Liuwei Dihuang Wan is beneficial to preventing and curing osteoporosis, but no correlation between its mechanism and the metabolism of 25(OH)D3 was demonstrated.

Animals↗

Building protein backbones from C alpha coordinates.

An automatic procedure for building polyalanine backbones from guiding alpha-carbon positions is presented. Polyalanine backbones are built based on the geometric restraints of angle N-C alpha-C and the knowledge of main-chain dihedral angle distributions. A building module constructs a list of polyalanine backbones that follow exactly the C alpha trace. Then a selection module selects one backbone with the largest portion of phi-psi pairs in favoured regions. Several test cases on C alpha coordinates from X-ray refined structures give acceptable results. Less than 10% of the peptide planes are incorrectly built, and the result is not sensitive to random shift up to 0.5 A of C alpha coordinates.

Amino Acid Sequence↗