Bis[3-chloro-6-(3,5-dimethyl-1H-pyrazol-1-yl)picolinato-κ3 O,N,N′]copper(II) tetra­hydrate

In the title complex, [Cu(C11H9ClN3O2)2]·4H2O, the CuII atom is in a distorted octa­hedral coordination environment, coordinated by four N atoms and two O atoms from two tridentate 3-chloro-6-(3,5-dimethyl-1H-pyrazol-1-yl)picolinate ligands. The mol­ecules are linked via inter­molecular O—H⋯O hydrogen bonds involving water mol­ecules to form extended chains along [010], and there are short Cl⋯Cl contacts [3.153 (4) Å]

State-of-art technologies to detect the DNA damage and repair in sperm and future outlook

Editorial - State-of-art technologies to detect the DNA damage and repair in sperm and future outloo

TMRT observations of 26 pulsars at 8.6 GHz

Integrated pulse profiles at 8.6~GHz obtained with the Shanghai Tian Ma Radio Telescope (TMRT) are presented for a sample of 26 pulsars. Mean flux densities and pulse width parameters of these pulsars are estimated. For eleven pulsars these are the first high-frequency observations and for a further four, our observations have a better signal-to-noise ratio than previous observations. For one (PSR J0742-2822) the 8.6~GHz profiles differs from previously observed profiles. A comparison of 19 profiles with those at other frequencies shows that in nine cases the separation between the outmost leading and trailing components decreases with frequency, roughly in agreement with radius-to-frequency mapping, whereas in the other ten the separation is nearly constant. Different spectral indices of profile components lead to the variation of integrated pulse profile shapes with frequency. In seven pulsars with multi-component profiles, the spectral indices of the central components are steeper than those of the outer components. For the 12 pulsars with multi-component profiles in the high-frequency sample, we estimate the core width using gaussian fitting and discuss the width-period relationship.Comment: 33 pages, 49 figures, 5 Tables; accepted by Ap

Sex-specific association of rs16996148 SNP in the NCAN/CILP2/PBX4 and serum lipid levels in the Mulao and Han populations

<p>Abstract</p> <p>Background</p> <p>The association of rs16996148 single nucleotide polymorphism (SNP) in <it>NCAN/CILP2/PBX4 </it>and serum lipid levels is inconsistent. Furthermore, little is known about the association of rs16996148 SNP and serum lipid levels in the Chinese population. We therefore aimed to detect the association of rs16996148 SNP and several environmental factors with serum lipid levels in the Guangxi Mulao and Han populations.</p> <p>Method</p> <p>A total of 712 subjects of Mulao nationality and 736 participants of Han nationality were randomly selected from our stratified randomized cluster samples. Genotyping of the rs16996148 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.</p> <p>Results</p> <p>The levels of apolipoprotein (Apo) B were higher in Mulao than in Han (<it>P </it>< 0.001). The frequencies of G and T alleles were 87.2% and 12.8% in Mulao, and 89.9% and 10.1% in Han (<it>P <</it>0.05); respectively. The frequencies of GG, GT and TT genotypes were 76.0%, 22.5% and 1.5% in Mulao, and 81.2%, 17.4% and 1.4% in Han (<it>P <</it>0.05); respectively. There were no significant differences in the genotypic and allelic frequencies between males and females in both ethnic groups. The levels of HDL-C, ApoAI, and the ratio of ApoAI to ApoB in Mulao were different between the GG and GT/TT genotypes in males but not in females (<it>P </it>< 0.01 for all), the subjects with GT/TT genotypes had higher serum levels of HDL-C, ApoAI, and the ratio of ApoAI to ApoB than the subjects with GG genotype. The levels of TC, TG, LDL-C, ApoAI, and ApoB in Han were different between the GG and GT/TT genotypes in males but not in females (<it>P </it>< 0.05-0.001), the T allele carriers had higher serum levels of TC, TG, LDL-C, ApoAI, and ApoB than the T allele noncarriers. The levels of HDL-C, ApoAI, and the ratio of ApoAI to ApoB in Mulao were correlated with the genotypes in males (<it>P </it>< 0.05-0.01) but not in females. The levels of TC, TG, HDL-C, LDL-C, ApoAI and ApoB in Han were associated with the genotypes in males (<it>P </it>< 0.05-0.001) but not in females. Serum lipid parameters were also correlated with several enviromental factors in both ethnic groups (<it>P </it>< 0.05-0.001).</p> <p>Conclusions</p> <p>The genotypic and allelic frequencies of rs16996148 SNP and the associations of the SNP and serum lipid levels are different in the Mulao and Han populations. Sex (male)-specific association of rs16996148 SNP in the <it>NCAN/CILP2/PBX4 </it>and serum lipid levels is also observed in the both ethnic groups.</p

Polymorphism of rs1044925 in the acyl-CoA:cholesterol acyltransferase-1 gene and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

<p>Abstract</p> <p>Background</p> <p>The association of rs1044925 polymorphism in the acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) gene and serum lipid profiles is not well known in different ethnic groups. Bai Ku Yao is a special subgroup of the Yao minority in China. The present study was carried out to clarify the association of rs1044925 polymorphism in the ACAT-1 gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.</p> <p>Methods</p> <p>A total of 626 subjects of Bai Ku Yao and 624 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of rs1044925 polymorphism in the ACAT-1 gene was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.</p> <p>Results</p> <p>The levels of serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (<it>P </it>< 0.01 for all). The frequency of A and C alleles was 79.0% and 21.0% in Bai Ku Yao, and 87.3% and 12.7% in Han (<it>P </it>< 0.001); respectively. The frequency of AA, AC and CC genotypes was 63.2%, 31.4% and 5.2% in Bai Ku Yao, and 75.6%, 23.2% and 1.1% in Han (<it>P </it>< 0.001); respectively. The levels of TC, LDL-C and ApoB in Bai Ku Yao but not in Han were different between the AA and AC/CC genotypes in females but not in males (<it>P </it>< 0.05 for all). The C allele carriers had lower serum TC, LDL-C and ApoB levels as compared with the C allele noncarriers. The levels of TC, LDL-C and ApoB in Bai Ku Yao but not in Han were correlated with genotypes in females but not in males (<it>P </it>< 0.05 for all). Serum lipid parameters were also correlated with sex, age, body mass index, alcohol consumption, and blood pressure in both ethnic groups (<it>P </it>< 0.05-0.001).</p> <p>Conclusions</p> <p>These results suggest that the polymorphism of rs1044925 in the ACAT-1 gene is mainly associated with female serum TC, LDL-C and ApoB levels in the Bai Ku Yao population. The C allele carriers had lower serum TC, LDL-C and ApoB levels than the C allele noncarriers.</p

Sex-specific association of ACAT-1 rs1044925 SNP and serum lipid levels in the hypercholesterolemic subjects

<p>Abstract</p> <p>Background</p> <p>Acyl-CoA:cholesterol acyltransferase (ACAT) is a key enzyme in cellular cholesterol homeostasis and in atherosclerosis. The cellular cholesterol efflux correlated with serum high-density lipoprotein cholesterol (HDL-C) concentrations has shown to be impaired in hyperlipidemic mice. The present study was carried out to clarify the association of ACAT-1 rs1044925 single nucleotide polymorphism (SNP) and serum lipid levels in the hyperlipidemic subjects.</p> <p>Methods</p> <p>A total of 821 unrelated subjects (hyperlipidemia, 476; normolipidemia, 345) aged 15-80 were included in the study. Genotyping of the ACAT-1 rs1044925 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.</p> <p>Results</p> <p>There was no significant difference in the genotypic and allelic frequencies of ACAT-1 rs1044925 SNP between the normolipidemic and hyperlipidemic subjects. The levels of total cholesterol (TC), HDL-C and apolipoprotein (Apo) AI in hyperlipidemic subjects were different between the AA and AC/CC genotypes in male but not in female (<it>P </it>< 0.05-0.01), the C allele carriers had higher serum TC, HDL-C and ApoAI levels than the C allele noncarriers. The association of genotypes and serum HDL-C and ApoAI levels in hyperlipidemia was found mainly in the male subjects with hypercholesterolemia but not in those with hypertriglyceridemia. There were no significant differences in serum lipid levels between the AA and AC/CC genotypes in the normolipidemic subjects.</p> <p>Conclusions</p> <p>The present study shows that the C allele carriers of ACAT-1 rs1044925 SNP in male hyperlipidemic subjects had higher serum TC, HDL-C and ApoAI levels than the C allele noncarriers. There is a sex (male)-specific association of ACAT-1 rs1044925 SNP and serum HDL-C and ApoAI levels in the hypercholesterolemic subjects.</p

The proprotein convertase subtilisin/kexin type 9 gene E670G polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

<p>Abstract</p> <p>Background</p> <p>Proprotein convertase subtilisin-like kexin type 9 (PCSK9) plays a key role in regulating plasma low-density lipoprotein cholesterol (LDL-C) levels. However, the association of E670G (rs505151) polymorphism in the PCSK9 gene and serum lipid levels is inconsistent in several previous studies. The present study was undertaken to detect the association of PCSK9 E670G polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.</p> <p>Methods</p> <p>A total of 649 subjects of Bai Ku Yao and 646 participants of Han were randomly selected from our previous samples. Genotypes of the PCSK9 E670G polymorphism were determined via polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.</p> <p>Results</p> <p>Serum levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), LDL-C, and apolipoprotein (Apo) AI were lower in Bai Ku Yao than in Han (<it>P </it>< 0.01 for all). The frequency of G allele was 2.00% in Bai Ku Yao and 4.80% in Han (<it>P </it>< 0.01). There was significant difference in the genotypic and allelic frequencies between Bai Ku Yao and Han (<it>P </it>< 0.01); between normal LDL-C (≤ 3.20 mmol/L) and high LDL-C subgroups (> 3.20 mmol/L, <it>P </it>< 0.01) in Bai Ku Yao; and between normal HDL-C (≥ 0.91 mmol/L) and low HDL-C (< 0.91 mmol/L, <it>P </it>< 0.05), between normal ApoAI (≥ 1.00 g/L) and low ApoAI (< 1.00 g/L, <it>P </it>< 0.05), or between normal ApoAI/ApoB ratio (≥ 1.00) and low ApoAI/ApoB ratio (< 1.00, <it>P </it>< 0.01) subgroups in Han. The G allele carriers in Han had higher serum HDL-C levels and the ratio of ApoAI to ApoB than the G allele noncarriers. The G allele carriers in Han had higher serum HDL-C and ApoAI levels than the G allele noncarriers in males (<it>P </it>< 0.05 for each), whereas the G allele carriers had lower serum ApoB levels and higher the ratio of ApoAI to ApoB than the G allele noncarriers in females (<it>P </it>< 0.05 for all). Serum HDL-C and ApoAI levels in Han were correlated with genotypes (<it>P </it>< 0.05) in males, and serum ApoB levels and the ratio of ApoAI to ApoB were associated with genotypes (<it>P </it>< 0.05) in females.</p> <p>Conclusions</p> <p>The PCSK9 E670G polymorphism is mainly associated with some serum lipid parameters in the Han population. The G allele carriers had higher serum HDL-C and ApoAI levels in males, and lower serum ApoB levels and higher the ApoAI/ApoB ratio in females than the G allele noncarriers.</p

DNA-PKcs plays a dominant role in the regulation of H2AX phosphorylation in response to DNA damage and cell cycle progression

<p>Abstract</p> <p>Background</p> <p>When DNA double-strand breaks (DSB) are induced by ionizing radiation (IR) in cells, histone H2AX is quickly phosphorylated into γ-H2AX (p-S139) around the DSB site. The necessity of DNA-PKcs in regulating the phosphorylation of H2AX in response to DNA damage and cell cycle progression was investigated.</p> <p>Results</p> <p>The level of γH2AX in HeLa cells increased rapidly with a peak level at 0.25 - 1.0 h after 4 Gy γ irradiation. SiRNA-mediated depression of DNA-PKcs resulted in a strikingly decreased level of γH2AX. An increased γH2AX was also induced in the ATM deficient cell line AT5BIVA at 0.5 - 1.0 h after 4 Gy γ rays, and this IR-increased γH2AX in ATM deficient cells was dramatically abolished by the PIKK inhibitor wortmannin and the DNA-PKcs specific inhibitor NU7026. A high level of constitutive expression of γH2AX was observed in another ATM deficient cell line ATS4. The alteration of γH2AX level associated with cell cycle progression was also observed. HeLa cells with siRNA-depressed DNA-PKcs (HeLa-H1) or normal level DNA-PKcs (HeLa-NC) were synchronized at the G1 phase with the thymidine double-blocking method. At ~5 h after the synchronized cells were released from the G1 block, the S phase cells were dominant (80%) for both HeLa-H1 and HeLa-NC cells. At 8 - 9 h after the synchronized cells released from the G1 block, the proportion of G2/M population reached 56 - 60% for HeLa-NC cells, which was higher than that for HeLa H1 cells (33 - 40%). Consistently, the proportion of S phase for HeLa-NC cells decreased to ~15%; while a higher level (26 - 33%) was still maintained for the DNA-PKcs depleted HeLa-H1 cells during this period. In HeLa-NC cells, the γH2AX level increased gradually as the cells were released from the G1 block and entered the G2/M phase. However, this γH2AX alteration associated with cell cycle progressing was remarkably suppressed in the DNA-PKcs depleted HeLa-H1 cells, while wortmannin and NU7026 could also suppress this cell cycle related phosphorylation of H2AX. Furthermore, inhibition of GSK3β activity with LiCl or specific siRNA could up-regulate the γH2AX level and prolong the time of increased γH2AX to 10 h or more after 4 Gy. GSK3β is a negative regulation target of DNA-PKcs/Akt signaling via phosphorylation on Ser9, which leads to its inactivation. Depression of DNA-PKcs in HeLa cells leads to a decreased phosphorylation of Akt on Ser473 and its target GSK3β on Ser9, which, in other words, results in an increased activation of GSK3β. In addition, inhibition of PDK (another up-stream regulator of Akt/GSK3β) by siRNA can also decrease the induction of γH2AX in response to both DNA damage and cell cycle progression.</p> <p>Conclusion</p> <p>DNA-PKcs plays a dominant role in regulating the phosphorylation of H2AX in response to both DNA damage and cell cycle progression. It can directly phosphorylate H2AX independent of ATM and indirectly modulate the phosphorylation level of γH2AX via the Akt/GSK3 β signal pathway.</p