920 research outputs found

    The splicing factor SR2 is an important virulence factor of Toxoplasma gondii

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    Serine/arginine-rich (SR) proteins are key factors with important roles in constitutive and alternative splicing (AS) of pre-mRNAs. However, the role of SR splicing factors in the pathogenicity of T. gondii remains largely unexplored. Here, weinvestigated the role of splicing factor SR2, a homolog of Plasmodium falciparum SR1, in the pathogenicity of T. gondii. Wefunctionally characterized the predicted SR2 in T. gondii by gene knockout and studied its subcellular localization by endogenous protein HA tagging using CRISPR-Cas9 gene editing. The results showed that SR2 was localized in the nucleus and expressed in the tachyzoite and bradyzoite stages. In vitro studies including plaque formation, invasion, intracellular replication, egress and bradyzoite dierentiation assays showed that deletion of SR2 in type I RH strain and type II Pru strains had no significant eect on the parasite growth and bradyzoite dierentiation (p> 0.05). Interestingly, the disruption of SR2 in RH type I (p < 0.0001) and Pru type II (p< 0.05) strains resulted in varying degrees of attenuated virulence. In addition, disruption of SR2in type II Pru strain significantly reduced brain cyst burden by ~80% (p< 0.0001). Collectively, these results suggest that splicing factor SR2 is important for the pathogenicity of T. gondii, providing a new target for the control and treatment of toxoplasmosis

    MicroRNA-1 acts as a tumor suppressor microRNA by inhibiting angiogenesis-related growth factors in human gastric cancer

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    Background We recently reported that miR-1 was one of the most significantly downregulated microRNAs in gastric cancer (GC) patients from The Cancer Genome Atlas microRNA sequencing data. Here we aim to elucidate the role of miR-1 in gastric carcinogenesis. Methods We measured miR-1 expression in human GC cell lines and 90 paired primary GC samples, and analyzed the association of its status with clinicopathological features. The effect of miR-1 on GC cells was evaluated by proliferation and migration assay. To identify the target genes of miR-1, bioinformatic analysis and protein array analysis were performed. Moreover, the regulation mechanism of miR-1 with regard to these predicted targets was investigated by quantitative PCR (qPCR), Western blot, ELISA, and endothelial cell tube formation. The putative binding site of miR-1 on target genes was assessed by a reporter assay. Results Expression of miR-1 was obviously decreased in GC cell lines and primary tissues. Patients with low miR-1 expression had significantly shorter overall survival compared with those with high miR-1 expression (P = 0.0027). Overexpression of miR-1 in GC cells inhibited proliferation, migration, and tube formation of endothelial cells by suppressing expression of vascular endothelial growth factor A (VEGF-A) and endothelin 1 (EDN1). Conversely, inhibition of miR-1 with use of antago-miR-1 caused an increase in expression of VEGF-A and EDN1 in nonmalignant GC cells or low-malignancy GC cells. Conclusions MiR-1 acts as a tumor suppressor by inhibiting angiogenesis-related growth factors in human gastric cancer. Downregulated miR-1 not only promotes cellular proliferation and migration of GC cells, but may activates proangiogenesis signaling and stimulates the proliferation and migration of endothelial cells, indicating the possibility of new strategies for GC therapy

    Surface-Based Regional Homogeneity in First-Episode, Drug-Naive Major Depression: A Resting-State fMRI Study

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    Background. Previous volume-based regional homogeneity (ReHo) studies neglected the intersubject variability in cortical folding patterns. Recently, surface-based ReHo was developed to reduce the intersubject variability and to increase statistical power. The present study used this novel surface-based ReHo approach to explore the brain functional activity differences between first-episode, drug-naive MDD patients and healthy controls. Methods. Thirty-three first-episode, drug-naive MDD patients and 32 healthy controls participated in structural and resting-state fMRI scans. MDD patients were rated with a 17-item Hamilton Rating Scale for Depression prior to the scan. Results. In comparison with the healthy controls, MDD patients showed reduced surface-based ReHo in the left insula. There was no increase in surface-based ReHo in MDD patients. The surface-based ReHo value in the left insula was not significantly correlated with the clinical information or the depressive scores in the MDD group. Conclusions. The decreased surface-based ReHo in the left insula in MDD may lead to the abnormal top-down cortical-limbic regulation of emotional and cognitive information. The surface-based ReHo may be a useful index to explore the pathophysiological mechanism of MDD.</p

    3,6-Dibromo-7-ethyl­amino-4-methyl-2H-chromen-2-one

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    In title compound, C12H11Br2NO2, the coumarin ring system is almost planar, the two rings being inclined to one another by 1.40 (15)°. There are two short intra­molecular inter­actions (N—H⋯Br and C—H⋯Br) involving the Br atoms. In the crystal, mol­ecules stack along the a-axis direction via π–π inter­actions; the centroid–centroid distances vary from 3.6484 (19) to 3.7942 (19) Å

    Effects of Malt Flour and Ascorbic Acid Additions on Bread Baking Quality

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    To study the effect of malt flour and ascorbic acid addition on the quality of bread baking, the sensory score, texture and c-cell product image changes of the breads with malt flour and ascorbic acid addition were studied by using 29 representative samples from two major wheat producing provinces of henan and shandong. The results showed that, the volume, the volume score, the appearance score and the final comprehensive score of bread were significantly improved after the addition of malt flour and ascorbic acid. The bread crown became larger and the neck became more prominent; however, the color, texture and texture structure of bread scores changes were not obvious. In the analysis of texture, the hardness and toughness decreased significantly, the attenuation ratio did not change obviously. The slice area, slice circumference, cell number and cell density of bread increased significantly in the analysis of c-cell results.The slice brightness and cell diameter of the slices decreased significantly. There is a correlation between the instrument evaluation index and some parameters in the bread sensory evaluation

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

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    <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

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    <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
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