Identification of a novel missense mutation in Brazilian patient with a severe form of mucopolysaccharidosis type IVA

Mucopolysaccharidosis type IVA (MPS IVA) or Morquio syndrome type A is an autosomal recessive disease caused by deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS). We report molecular characterization of a patient who presents the new missense mutation p.C165Y in homozygosis. Bioinformatics analysis predicted this mutation as being probably pathogenic. To evaluate the possibility that this alteration was a polymorphism we tested 100 alleles and all the results were negative. These findings together with the observation that this alteration is not present in controls, suggest that it is a disease-causing mutation, which was correlated with the severe phenotype observed in our patient. We conclude that molecular analysis of the GALNS gene, in addition to enzyme assays, is important for diagnosis and contributes to the better understanding of the relationship between genotype and phenotype, which is important as enzyme replacement therapy (ERT) will soon become available and treatment decisions will have to be take in such cases.     

基于同位素标记相对和绝对定量技术研究耐铬(VI)菌株CM01的蛋白定量组学

【背景】六价铬[Cr(VI)]作为一种高毒性的重金属污染物,用微生物学方法还原Cr(VI)既经济又环保。【目的】探究耐铬菌株CM01中与耐受或还原铬Cr(VI)有关的蛋白或基因,从分子水平上阐述其耐铬Cr(VI)机制。【方法】运用同位素标记相对和绝对定量技术(isobarictagsforrelativeand absolute quantitation techniques,iTRAQ)分析耐铬菌株CM01在有无铬Cr(VI)胁迫下的蛋白表达差异。运用RT-qPCR技术验证4种与代谢途径有关的上调蛋白的m RNA表达量。运用紫外分光光度计测定细胞表面疏水性。【结果】共鉴定到2 570个蛋白,其中存在显著差异的蛋白数为646个,上调蛋白数量343个,下调蛋白数量303个。CM01中的Fe/Mn超氧化物歧化酶、甜菜碱醛脱氢酶、磷酸戊糖途径、磷酸肌醇代谢途径、氨基酸代谢共同参与了菌株对于外源性Cr(VI)的响应机制。RT-qPCR实验结果表明,与代谢途径有关的4种蛋白其基因转录水平和蛋白水平一致。对照组CM01的细胞表面疏水性高于实验组。【结论】初步探索了耐铬菌的Cr(VI)响应机制,为利用微生物治理环境污染提供了理论支持和新的研究思路。     

不同制剂中相同中草药薄层色谱鉴别探讨

目的探讨不同制剂中相同中药材统一鉴别的可行性。方法采用薄层色谱法,取不同制剂适量,按统一方法制备供试液、层析条件、显色与检视斑点。结果多种含大黄、人参的制剂,薄层色谱斑点清晰明显。结论本实验方法可行,在不同制剂中相同药材鉴别有较统一的方法为好。     

不同浓度罗哌卡因复合右美托咪定在肛肠疾病日间手术中的麻醉效果研究

目的:研究不同浓度罗哌卡因复合右美托咪定在肛肠疾病日间手术中的麻醉效果。方法:选取2016年5月～2018年5月期间于我院行肛肠疾病日间手术的患者123例为研究对象。根据随机数字表将患者分成A、B、C三组,每组各41例,其中A组麻醉时注入右美托咪定复合0.375%罗哌卡因20 m L,B组麻醉时注入右美托咪定复合0.5%罗哌卡因20 m L,C组注入右美托咪定复合0.75%罗哌卡因20 m L。比较三组患者麻醉后镇痛效果,比较三组麻醉前、麻醉30 min后的呼吸循环指标,比较三组患者感觉神经、运动神经阻滞情况,记录三组患者术后不良反应发生情况。结果:B组、C组镇痛优良率显著高于A组(P0.05),但B组、C组镇痛优良率组间比较差异无统计学意义(P0.05)。三组患者麻醉前、麻醉30 min后心率(HR)、收缩压(SBP)、舒张压(DBP)、血氧饱和度(SPO2)整体比较差异均无统计学意义(P0.05)。B组、C组感觉神经阻滞起效时间均较A组短,且C组短于B组(P0.05),而B组、C组感觉神经阻滞持续时间均较长,且C组长于B组(P0.05);B组、C组Bromage评分1分人数均较A组少,且C组少于B组(P0.05),B组、C组Bromage评分2分人数均较A组多,但C组较B组少(P0.05),C组Bromage评分3分人数较A组和B组多(P0.05),三组Bromage评分4分人数整体比较差异均无统计学意义(P0.05)。C组患者术后不良反应总发生率高于A组、B组(P0.05),但A组、B组不良反应总发生率组间比较差异无统计学意义(P0.05)。结论:0.5%、0.75%罗哌卡因复合右美托咪定应用于肛肠疾病日间手术的镇痛效果、麻醉效果优于0.375%罗哌卡因复合右美托咪定,但是0.75%罗哌卡因复合右美托咪定的不良反应发生率偏高,0.5%罗哌卡因复合右美托咪定是肛肠疾病日间手术中更为合适的麻醉方案。     

Two genetic variants in FABP1 and susceptibility to non-alcohol fatty liver disease in a Chinese population

Liver fatty acid-binding protein (FABP1) serves as a key regulator of hepatic lipid metabolism, and polymorphisms within the FABP1 gene have been associated with several metabolic traits. To investigate the association between FABP1 polymorphisms and the risk of non-alcohol fatty liver disease (NAFLD) in a Chinese population, the genotypes and haplotypes of FABP1 (rs2241883 T/C and rs1545224G/A) were determined in 553 patients with NAFLD and 553 healthy controls. The results showed that individuals with at least one copy of the rs2241883 C allele (TC or CC genotype) had an elevated risk for developing NAFLD (odds ratio [OR]=1.32, 95% CI: 1.01-1.71), and individuals with at least one copy of the rs1545224 A allele (GA or AA genotype) also had a significantly increased risk for NAFLD (OR=1.52, 95% CI: 1.14-2.02). Cumulative effect analysis of the two SNPs revealed that individuals with two risk genotypes were at significantly higher risk of NAFLD than those without risk genotype, and a significant trend of increased risk with increasing numbers of risk genotype was observed. Stratification analysis showed that the rs2241883 C allele carriers had higher level of LDL-C and the rs1545224 A allele carriers had higher level of FPG than those without this allele. In addition, haplotype analysis revealed that the one composed of the rs1545224 A and rs2241883 C variants was significantly associated with an increased risk for NAFLD (OR=1.34; 95% CI=1.05-1.40) compared to the GT haplotype. Taken together, the present study suggests that genetic variations within FABP1 influence susceptibility to NAFLD independently or jointly.     

The function and structural influence of selective relaxed constraint at functional intracellular loop3 of 5-HT1A serotonin-1 receptor family

Serotonin (5-HT) and its receptors have been involved in critical signal transduction mechanism and deregulation implicated in mood-related disorders. 5-HT activities are mediated through a family of transmembrane spanning serotonin receptors. Both within the family and species, 5-HT receptor protein sequence diversity and 7-transmembrane structural homogeneity have long been intriguing. In this study, we have analyzed the codon site constraint in 5-HT1 subclass receptors from 13 orthologous mammalian mRNA coding sequence. Further, the study was extended to computationally investigate the impact of non-synonymous sites with respect to function and structural significance through sequence homology algorithm and molecular dynamics simulation (MDS). Codon sites with significant posterior probability were observed in 5-HT_1A, 5‐HT_1B and 5-HT_1D receptor indicating variations in site constraint within the 5‐HT1 sub-class genes. In 5-HT_1A receptor, seven sites were detected at the functional intracellular loop₃ (ICL₃) with higher substitution rate through Codeml program. Sequence homology algorithm identifies that these sites were functionally tolerant within the mammals representing a selectively relaxed constraint at this domain. On the other hand, the root mean square deviation (rmsd) values from MDS suggest differences in structural conformation of ICL₃ models among the species. Specifically, the human ICL₃ model fluctuation was comparatively more stable than other species. Hence, we argue that these sites may have varying influence in G-proteins coupling and activation of effectors systems through downstream interacting accessory proteins of cell among the species. However, further experimental studies are required to elucidate the precise role and the seeming difference of these sites in 5-HT receptors between species.     

Effects of local elastic compression on muscle strength, electromyographic, and mechanomyographic responses in the lower extremity

The purpose of this study was to investigate the effect of elastic compression on muscle strength, electromyographic (EMG), and mechanomyographic (MMG) responses of quadriceps femoris during isometric and isokinetic contractions. Twelve participants performed 5 s isometric maximal voluntary contractions (MVC) and 25 consecutive and maximal isokinetic knee extensions at 60 and 300 °/s with no (control, CC), medium (MC), and high (HC) compression applied to the muscle. The EMG and MMG signals were collected simultaneously with muscle isometric and isokinetic strength data. The results showed that the elevated compression did not improve peak torque, peak power, average power, total work, and regression of torque in the isometric and isokinetic contractions. However, the root mean squared value of EMG in both HC and MC significantly decreased compared with CC at 60 and 300 °/s (p < 0.01). Furthermore, the EMG mean power frequency in HC was significantly higher than that in CC at 60 °/s (p < 0.05) whereas no significant compression effect was found in the MMG mean power frequency. These findings provide preliminary evidence suggesting that the increase in local compression pressure may effectively increase muscle efficiency and this might be beneficial in reducing muscle fatigue during concentric isokinetic muscle contractions.     

Response to: Comment on 'Visual cues override olfactory cues in the host-finding process of the monophagous leaf beetle Altica engstroemi'

Intake rates by the Queensland fruit fly, Bactrocera tryoni (Froggatt) (Diptera: Tephritidae), of yeast autolysate and sucrose were clearly related to temperature in constant thermal regimes, but consumption occurred only in light. In regimes of fluctuating temperature, rates of consumption were not necessarily related to the temperatures that prevailed during the photophase, but were more consistently related to daily mean temperature and best related to day degrees per day above the gonadotrophic threshold of 13.5 °C. Day degrees per day could be related to age‐specific changes in the daily rate of yeast autolysate and sucrose consumption, the rate of accumulated consumption of these foods, and thus the time taken to consume the amount of yeast autolysate known to be required for the attainment of sexual maturity. Consumption rate changed within 1 or 2 days of a change between a gonadotrophic regime and a non‐gonadotrophic one (or vice versa), which is consistent with the known rapid effects of temperature change on ovarian maturation.     

Phytochemical study on the leaves of Wollemia nobilis

In this work, a phytochemical study performed on the leaves of the rare species, Wollemia nobilis W.G. Jones, K.D. Hill & J.M. Allen, is reported. By means of classical column chromatography and NMR Spectroscopy and Mass Spectrometry, nine compounds were evidenced. These were: pheophorbide a (1), isocupressic acid (2), acetyl-isocupressic acid (3), sandaracopimaric acid (4), agathic acid (5), 7–4′-4‴-tri-O-methyl-agathisflavone (6), 7–4′-7″-4‴-tetra-O-methyl-agathisflavone (7), caffeic acid (8) and shikimic acid (9). Compared to our previous phytochemical analysis on the male cones, some further compounds were identified i.e. compounds 1, 5, 6, 7 and 8. This confirmed the previous chemotaxonomic considerations of the species but also added new ones which were discussed within the text. In addition, a possible different accumulation of secondary metabolites in the tissues and organs of this plant was even noticed.     

不同剂量瑞舒伐他汀钙对老年冠心病合并高脂血症患者血脂水平的影响分析

目的:探讨在瑞舒伐他汀不同剂量下对治疗对冠心病合并高血脂症的老年患者的血脂功能水平的影响。方法:回顾性选取我院接诊的冠心病老年患者120例,且经过血脂检查全部属于高血脂症,按照使用瑞舒伐他汀的剂量不同,分为三组各40例患者,分别给予剂量为5 mg、10 mg和20 mg,以治疗后2个月为观察期,比较治疗前后患者的血脂水平变化及临床有效率。结果:(1)20mg组患者的血脂水平HDL-C[(1.17±0.62)mmol/L]比其他两组明显上升,LDL-C[(3.67±0.83)mmol/L]、TC[(4.36±0.96)mmol/L]、TG[(1.68±0.94)mmol/L]也下降较另外两组明显(P均0.05);(2)20 mg组的治疗有效率为(97.5%)明显高于5mg组(87.5%)和10mg组(85.0%)(P均0.05)。结论:瑞舒伐他汀治疗冠心病合并高血脂症的老年患者,选择20 mg剂量可显著改善患者的血脂水平,且具有较高的治疗有效率,是一种使用方便,临床效果明显的给药方式。