Direct structural insight into the substrate-shuttling mechanism of yeast fatty acid synthase by electron cryomicroscopy

Yeast fatty acid synthase (FAS) is a 2.6-MDa barrel-shaped multienzyme complex, which carries out cyclic synthesis of fatty acids. By electron cryomicroscopy of single particles we obtained a three-dimensional map of yeast FAS at 5.9-Å resolution. Compared to the crystal structures of fungal FAS, the EM map reveals major differences and new features that indicate a considerably different arrangement of the complex in solution compared to the crystal structures, as well as a high degree of variance inside the barrel. Distinct density regions in the reaction chambers next to each of the catalytic domains fitted the substrate-binding acyl carrier protein (ACP) domain. In each case, this resulted in the expected distance of ∼18 Å from the ACP substrate-binding site to the active site of the catalytic domains. The multiple, partially occupied positions of the ACP within the reaction chamber provide direct structural insight into the substrate-shuttling mechanism of fatty acid synthesis in this large cellular machine.     

Understanding sickle cell carrier status identified through newborn screening: a qualitative study

The expansion of newborn screening (NBS) is increasing the generation of incidental results, notably carrier results. Although carrier status is generally understood to be clinically benign, concerns persist that parents may misunderstand its meaning, with deleterious effects on children and their families. Expansion of the NBS panel in Ontario, Canada in 2006 to include sickle cell disorders drew attention to the policy challenge of incidental carrier results. We conducted a study of consumer and provider attitudes to inform policy on disclosure. In this paper, we report the results of (i) qualitative interviews with health-care providers, advocates and parents of carrier infants and (ii) focus groups with new parents and individuals active with the sickle cell community. Lay and provider participants generally believed that carrier results were clinically insignificant. However, some uncertainty persisted among lay consumers in the form of conjecture or doubt. In addition, consumers and advocates who were most informed about the disease articulated insistent yet dissonant claims of clinical significance. Meanwhile, providers referenced research knowledge to offer an equivocal assessment of the possibility and significance of clinically symptomatic carrier status. We conclude that many interpretations of carrier status are in circulation, failing to fit neatly into the categories of ‘clinically significant'' or ‘benign.'' This creates challenges for communicating clearly with parents – challenges exacerbated by inconsistent messages from screening programs regarding the significance of sickle cell carrier status. Disclosure policy related to incidentally generated infant carrier results needs to account for these complex realities.     

Carrier testing and prenatal diagnosis of haemophilia — utilisation and psychological consequences

Summary. Attitudes towards prenatal diagnosis, and abortion vary widely between different countries, religions, cultures and over time. Carrier testing and prenatal diagnosis (PD) of haemophilia have become an integrated part of the comprehensive care for haemophilia in Sweden as well as in many other countries. Almost all carriers are interested in carrier testing if they are aware of the possibility. With the development of PD by chorionic villus sampling in the first trimester, the method became acceptable for many carriers, and it has in Sweden actually had an effect on the incidence of haemophilia in the 1990s. The use of PD is more common among women who perceive haemophilia as a very serious disease and who have a positive attitude towards legal abortion. The main reason for carriers not to use PD was that they do not find haemophilia to be a sufficiently serious disorder to justify an abortion. Women and their spouses are under a great deal of psychological pressure in association with the PD procedure, and the psychological consequences of having to terminate a pregnancy are long-lasting. At follow-up, about 6 years after PD and abortion, these women, however, do not have more signs of psychological distress than women without PD experience. Nevertheless, they must be offered qualified assistance both before and after PD as well as adequate follow-up after an abortion to help them cope with the emotional strain they are under.     

2009-2013年兴安盟手足口病疫情分析

目的 了解兴安盟地区手足口病流行特征和病原种类,为制定防控策略提供科学依据.方法 采用描述性流行病学方法描述2009至2013年兴安盟手足口病流行特征,采用分析性统计学方法分析病原检测结果.结果 2009至2013年全盟共报告手足口病病例3655例,各年发病率依次为113.71/10万、32.09/10万、18.78/10万、27.64/10万和27.49/10万,2009至2013年手足口病报告发病数居丙类传染病首位,发病高峰为6至7月,≤3岁组病例占发病总数的58.22％;2009至2013年兴安盟疾病预防控制中心共检测了952标本,检出阳性标本77份,其中EV71阳性标本33份,占实验室诊断病例总数的42.86％;CA16阳性标本15份,占19.48％;其他肠道病毒阳性标本29份,占37.66％.结论 2009至2013年兴安盟地区手足口病疫情比较平稳,发病有明显的季节性,散居儿童是主要发病人群;主要病原是EV71和CA16,EV71为优势流行株.     

血脑屏障上的转运蛋白及中药有效成分跨血脑屏障转运研究进展

本文介绍了血脑屏障的结构、功能及该部位的转运蛋白(ATP结合盒转运蛋白和溶质载体转运蛋白),以及它们在血脑屏障转运过程中的作用.通过脑微血管内皮细胞模型和在体脑微透析技术,定性定量地探讨了转运蛋白在中药有效成分跨血脑屏障中的作用.     

240例眼部感染患者病原菌分布及耐药性分析

目的 了解眼部感染患者病原菌分布及耐药情况,为临床药物合理使用提供依据.方法 采用Kirby-Bauer(K-B)法进行药敏试验,数据分析采用WHONET 5.6软件.结果 占眼部感染比例前两位的病原菌分别是凝固酶阴性葡萄球菌(CNS)和大肠埃希菌.前者对左旋氧氟沙星和庆大霉素的耐药率(24.2％和18.9％)远低于β-内酰胺类和大环内酯类;后者对大部分抗菌药物具有较低的耐药率,其中包括阿米卡星和环丙沙星(0％和27.3％).结论 眼部感染前两位病原菌分别是CNS和大肠埃希菌,两者都对喹诺酮类药物和氨基糖苷类药物有较低的耐药率,可以做为治疗眼部感染的首选药物.     

A convenient method for the preparation of radioiodinated meta‐iodobenzylguanidine at a no‐carrier‐added level

Radioiodinated meta‐iodobenzylguanidine (MIBG) in high effective specific activity was prepared using 3‐tributylstannylbenzylguanidine as the precursor. The labeling was carried out in aqueous solution with the insoluble and lyophilized precursor suspended in the solvent. Simply by filtration, the starting material and by‐products were readily separated from the labeled solution. Less than 1.15 ppb tin has remained in the filtrate as determined by the atom fluorescence spectrometry. By this approach, high specific activity (3.4 GBq/µmol) [¹³¹I]MIBG was obtained in 72.3 ± 3% (n = 3) radiochemical yield and 97.3 ± 2% (n = 3) radiochemical purity. The whole preparation could be finished in less than 10 min. According to this method, a kit for the preparation of ¹²³I‐MIBG and ¹³¹I‐MIBG is currently being developed.     

神经外科患者围手术期感染病原菌调查分析

目的了解神经外科患者围手术期感染病原菌的构成特点,为临床诊治及科学选药提供依据。方法回顾性统计分析2010年8月-2013年7月神经外科患者病原学标本中分离出的阳性病原菌和药敏监测资料,药敏试验采用K-B纸片法。结果神经外科患者围手术期感染病原菌标本来源以痰液和粪便标本为主,分别占59.49%和25.90%;共分离病原菌390株,其中革兰阴性菌199株占51.02%,革兰阳性菌65株占16.67%,真菌126株占32.31%;主要革兰阴性菌和革兰阳性菌对多数青霉素类、头孢菌素类、喹诺酮类的耐药率>70.00%,假丝酵母菌属对益康唑、伊曲康唑和酮康唑也有少数耐药现象。结论神经外科感染病原菌以革兰阴性菌为主,主要病原菌对常用抗菌药物均产生了较严重的耐药性,临床应针对感染的高危因素严格落实各项控制措施,根据药敏结果合理选择抗菌药物。     

NICU新生儿感染病原菌分布及耐药性分析

目的探讨新生儿重症监护病房(NICU)病原菌分布及耐药性,为临床合理用药提供科学依据。方法选取2011年3月-2013年10月NICU感染患儿360例,采集患儿血液等标本进行病原菌检测和药物敏感试验,分析病原菌分布及其耐药性。结果 360例患儿共分离出病原菌395株,其中革兰阴性菌232株占58.7%,革兰阳性菌129株占32.7%,真菌34株占8.6%;革兰阴性菌对喹诺酮类、氨基糖苷类、第三代头孢菌素等抗菌物耐药率较高,多数>90.00%,部分达100.00%,耐药率较低的是亚胺培南、头孢哌酮/舒巴坦、哌拉西林/他唑巴坦,主要革兰阳性菌对克林霉素、左氧氟沙星、红霉素、青霉素有较高的耐药性,多数>90.00%,部分达100.00%,真菌的耐药率普遍较低。结论 NICU患儿感染病原菌分布以革兰阴性菌为主,临床用药应该尽量避免经验用药,根据药敏结果进行针对性选择用药。