一例ALMS1基因复合杂合突变所致的Alstrom综合征的诊疗和基因检测分析

Alstrom综合征是一种由ALMS1基因突变导致的罕见的常染色体隐性遗传病,以锥杆型视网膜营养不良、感音神经性耳聋、肥胖、胰岛素抵抗、糖尿病、高甘油三酯血症、非酒精性脂肪肝、扩张性心肌病、进行性肝肾功能障碍为典型临床表现。本文随访1例以糖尿病就诊的青年男性患者,合并有失明、耳聋、高脂血症、肥胖、脂肪肝、胰岛素抵抗,基因检测结果表明患者ALMS1基因发生复合杂合突变,分别来源于母亲和父亲,前者为8号外显子携带的突变c.5535delG(p.S1847Lfs*24),后者为16号外显子携带的突变c.10819C>T(p.R3607X),这两个突变位点在已知的ALMS1基因变异库中均未被报道。该患者口服达格列净后,高胰岛素正葡萄糖钳夹实验发现其胰岛素敏感性指数显著提高。通过总结分析该病例,对于临床上青少年起病的合并有失明、耳聋、严重胰岛素抵抗和脂代谢紊乱的糖尿病患者,应考虑到Alstrom综合征的可能。本病例发现的2个新突变位点丰富了ALMS1基因的遗传变异数据库,其治疗随访数据为该类疾病患者选择合适的降糖方案提供了新的证据。

Torque and Topology of Braided DNAs under Tension

Double helix DNAs become intertwined around one another during replication and recombination.Here we used magnetic tweezers to make braided DNA molecules and measured their torques under various catenations(Ca)at forces ranging from 0.3 to 8 pN.Images of braided DNA constructs under tensions were captured by scanning electron microscopy which showed major and minor grooves of DNAs and plectonemes of the braids.When the two DNA molecules were braided,the extension decreased as the catenation increased from 0 to 50 turns.We used a thermodynamic Maxwell relation to deduce the torque by integrating the change in the braid extension as a function of the force.The torque increased with the catenation,force and intertether distance until the catenation reached a buckling point.Under the condition of 2 pN force and Ca=20,the torque was computed to be 31,21 and 15 pN nm for the braids of which the intertether distances were 54%,31%and 26%of the DNA contour length,respectively.At an 8.03 pN holding force,the torque was computed to be 76 pN nm as the catenation increased from 0 to 30 turns,or as the catenation density varied from 0 to 0.053.The torque reached a plateau when the catenation increased above 20,indicating formation of braid-plectonemes.The twist modulus increased with the catenation prior to reaching a peak.Before reaching the peak,the moduli were higher than those of a single twisted DNA under the same catenation and applied force.Our experimental data agrees well with the calculation results by a recently developed semiflexible polymer model.Our measurements of the nonlinear torque of the braid establish new fundamental properties of DNA intertwining,which is key to understanding DNA replication and gene expression.The speaker will also introduce briefly other projects in the Xiao group including direct measurements of theforce spectrum of single unlabeled proteins such as adhesive nano-fibers for biofilm,the screening of integrin-targeted peptides drugs by single cell approaches,and the micromechanical approach for determining the survival rate of stem cells.

mDRA-6与尼美舒利对人肝癌细胞系SMMC-7721细胞的协同杀伤效应(英文)

Objective: The aim of this work was to evaluate anti-tumor effects of mDRA-6 plus nimesulide on a human hepatocellular cancer cell line, SMMC-7721, and study the main mechanisms. Methods: The DR5 receptor of SMMC-7721 cells was detected by flow cytometry (FCM). For further experimental application, SMMC-7721 cells were treated with proper dose of mDRA-6, nimesulide, or mDRA-6 plus 200 μmol/L nimesulide; untreated SMMC-7721 cells were comparably set as control. Cytotoxicity was tested by MTT assay; cell morphology was examined using Hoechst 33258 staining; and apoptosis was determined by FCM. Results: The positive rate of DR5 on SMMC-7721 was 95.0%. Either mDRA-6 or nimesulide alone induces SMMC-7721 cell death in a dose-dependent manner. Treatment of 1,600 ng/mL mDRA-6 for 12h led to a cell-death rate of 35.0%, while an increased cell-death rate (91.1%) was found under the same condition of mDRA-6 treatment supple- mented with 200 μmol/L nimesulide. Hoechst 33258 and Annexin V/PI staining confirmed apoptosis as the main cause of this anti-tumor response. Conclusion: Both mDRA-6 and nimesulide can induce apoptosis of SMMC-7721 cells, and they have synergistic anti-tumor activities against SMMC-7721.

Emissions of polycyclic aromatic hydrocarbons from coking industries in China

This study set out to assess the characteristics of polycyclic aromatic hydrocarbon （PAH） emission from coking industries, with field samplings conducted at four typical coke plants. For each selected plant, stack flue gas samples were collected during processes that included charging coal into the ovens （CC）, pushing coke （PC） and the combustion of coke-oven gas （CG）. Sixteen individual PAHs on the US EPA priority list were analyzed by gas chromatography/mass spectrometry （GC/MS）. Results showed that the total PAH concentrations in the flue gas ranged from 45.776 to 414.874 μg/m3, with the highest emission level for CC （359.545μg/m3）, The concentration of PAH emitted from the CC process in CP1 （stamp charging） was lower than that from CP3 and CP4 （top charging）. Low-molecular-weight PAHs （i.e., two- to three-ring PAHs） were predominant contributors to the total PAH contents, and Nap, AcPy, Flu, PhA, and AnT were found to be the most abundant ones. Total BaPeq concentrations for CC （2.248 μg/m3） were higher than those for PC （ 1.838 μg/m3 ） and CG （1.082 μg/m3 ）, and DbA was an important contributor to carcinogenic risk as BaP in emissions from coking processes. Particulate PAH accounted for more than 20% of the total BaPeq concentrations, which were significantly higher than the corresponding contributions to the total PAH mass concentration （5%）. Both particulate and gaseous PAH should be taken into consideration when the potential toxicity risk of PAH pollution during coking processes is assessed. The mean total-PAH emission factors were 346.132 and 93.173μg/kg for CC and PC, respectively.