大肠埃希菌氨基糖苷酰基转移酶基因型研究

目的：了解大肠埃希菌的耐药谱、氨基糖苷酰基转移酶基因（aac）的分布规律及其与氨基糖苷类抗生素耐药的相关性。方法：琼脂稀释法测定无菌体液分离的44株大肠埃希菌对阿米卡星等12种抗生素的耐药性，聚合酶联反应（PCR）法测定酰基转移酶基因型aac（3）-Ⅰ、Ⅱ和aac（6’）-Ⅰ。结果：大肠埃希菌超广谱β-内酰胺酶（ESBLs）的发生率为45．45％（20／44），对亚胺培南（IPM）、关罗培南（MEM）的耐药率为0，对哌拉西林／他唑巴坦、头孢他啶的耐药率较低（〈20％），对左氟沙星、环丙沙星的耐药率较高（〉60％），对氨基糖苷类阿米卡星、庆大霉素、妥布霉素的耐药率分别为18．18％、56．82％、61．36％。氨基糖苷类耐药模式TG（妥布霉素、庆大霉素）〉TGA（妥布霉素、庆大霉素、阿米卡星）〉T（妥布霉素）〉G（庆大霉素），分别占36．36％、18．189／5、6．82％、2．27％。氨基糖苷酰基转移酶基因检出以aac（3）-Ⅱ最高，占52．27％（23／44），aac（6＇）-Ⅰ次之，占29．55％（13／44），aac（3）-Ⅱ和aac（6’）-Ⅰ同时检出者占15．91％（7／44），未检出aac（3）-Ⅰ。ESBLs阳性株的aac（3）-Ⅱ、aac（6’）-Ⅰ检出率分别为60％、50％，高于ESBLs阴性株的45．81％、12．51％。TG模式与其耐药基因aac（3）-Ⅱ符合率较高为93．75％（15／16）。结论：本地分离大肠埃希菌氨基糖苷类耐药模式以TG为主，酰基转移酶基因以aac（3）-Ⅱ为主，aac（6’）-Ⅰ次之，aac（3）-Ⅰ罕见。     

Stability and specificity of heterodimer formation for the coiled‐coil neck regions of the motor proteins Kif3A and Kif3B: the role of unstructured oppositely charged regions

Abstract: We investigated the folding, stability, and specificity of dimerization of the neck regions of the kinesin‐like proteins Kif3A (residues 356–416) and Kif3B (residues 351–411). We showed that the complementary charged regions found in the hinge regions (which directly follow the neck regions) of these proteins do not adopt any secondary structure in solution. We then explored the ability of the complementary charged regions to specify heterodimer formation for the neck region coiled‐coils found in Kif3A and Kif3B. Redox experiments demonstrated that oppositely charged regions specified the formation of a heterodimeric coiled‐coil. Denaturation studies with urea demonstrated that the negatively charged region of Kif3A dramatically destabilized its neck coiled‐coil (urea_1/2 value of 3.9 m compared with 6.7 m for the coiled‐coil alone). By comparison, the placement of a positively charged region C‐terminal to the neck coiled‐coil of Kif3B had little effect on stability (urea_1/2 value of 8.2 m compared with 8.8 m for the coiled‐coil alone). The pairing of complementary charged regions leads to specific heterodimer formation where the stability of the heterodimeric neck coiled‐coil with charged regions had similar stability (urea_1/2 value of 7.8 m ) to the most stable homodimer (Kif3B) with charged regions (urea_1/2 value of 8.0 m ) and dramatically more stable than the Kif3A homodimer with charged regions (urea_1/2, value of 3.9 m ). The heterodimeric coiled‐coil with charged extensions has essentially the same stability as the heterodimeric coiled‐coil on its own (urea_1/2 values of 7.8 and 8.1 m , respectively) suggesting that specificity of heterodimerization is driven by non‐specific attraction of the oppositely unstructured charged regions without affecting stability of the heterodimeric coiled‐coil.     

Monomeric and dimeric states exhibited by the kinesin‐related motor protein KIF1A

Abstract: KIF1A, a kinesin‐related motor protein that transports pre‐synaptic vesicles in neurons, was originally presumed to translocate along microtubules (MT) as a monomer. Protein structure predictions from its amino acid sequence failed to identify the long coiled‐coil domains typical of kinesins, which led researchers to believe it does not oligomerize into the canonical kinesin dimer. However, mounting evidence using recombinant chimeric protein indicates that KIF1A, like conventional kinesin, requires dimerization for fast, unidirectional processive movement along MTs. Because these studies are somewhat indirect, we wished to test the oligomerization state of native KIF1A, and to compare that to full‐length recombinant protein. We have performed hydrodynamic analyses to determine the molecular weights of the respective complexes. Our results indicate that most native KIF1A is soluble and indeed monomeric, but recombinant KIF1A is a dimer. MT‐binding studies also showed that native KIF1A did not bind to MTs in either the presence of AMP‐PNP, apyrase, or adenosine triphosphate (ATP), but recombinant KIF1A bound to MTs most stably in the presence of ATP, indicating very different motor functional states. To further characterize KIF1A's dimerization potential, we prepared peptides corresponding to the neck domains of MmKIF1A and CeUnc104, and by circular dichroism spectroscopy compared these peptides for their ability to form coiled‐coils. Interestingly, both MmKIF1A and CeUnc104 neck peptides formed homodimeric coiled‐coils, with the MmKIF1A neck coiled‐coil exhibiting the greater stability. Collectively, from our data and from previous studies, we predict that native KIF1A can exist as both an inactive monomer and an active homodimer formed in part through its neck coiled‐coil domain.     

蚊香烟尘和焦油的测定及对小鼠的影响

目的测定蚊香燃烧时产生的烟尘和焦油量,并研究其产生的毒性.方法采用物理方法测定三种类型蚊香的烟尘和焦油量,并用小鼠做经口和吸入毒性实验.结果不同类型的蚊香产生的烟尘和焦油量不同,微烟蚊香焦油含量是无烟蚊香的3倍,绿蚊香的焦油量比微烟蚊香高1倍.微香蚊香的烟尘量是无烟蚊香的4倍,绿/黄蚊香的烟尘量比微烟蚊香高1～3倍,小鼠经吸入3种蚊香不同浓度的烟尘后,出现不同程度的中毒症状,并导致体重降低,摄食量减少,高剂量时还可造成肺和气管充血或水肿等症状.结论不同类型的蚊香产生的烟尘和焦油量有很大差异,过多的烟尘和焦油量对小鼠健康会造成不同程度的影响,因此选择使用烟尘和焦油量适中的蚊香灭蚊有利于提高人们生活质量,减少对环境的污染.     

Long acting reversible contraception

Long-acting reversible contraception (LARC) is the collective name for intrauterine contraception (copper intrauterine devices and levonorgestrel intrauterine systems) and the subdermal contraceptive implant. LARC methods are highly effective, require minimal user effort and do not require regular healthcare appointments; however the insertion and removal procedures can only be undertaken by clinicians trained to do so. The progestogen-only subdermal implant is the most effective method of reversible contraception in the United Kingdom and is licensed for 3 years. The copper intrauterine device is the most effective non-hormonal method of contraception. These devices are licensed for five or 10 years and can also be used as emergency contraception. The levonorgestrel intrauterine systems (LNG-IUS) are licensed for 3, 5, or 6 years. The Mirena LNG-IUS is also licensed for use in treating heavy menstrual bleeding and for endometrial protection as part of hormone replacement therapy.     

Whole‐body radiofrequency coil for 31P MRSI at 7 T

Widespread use of ultrahigh‐field ³¹P MRSI in clinical studies is hindered by the limited field of view and non‐uniform radiofrequency (RF) field obtained from surface transceivers. The non‐uniform RF field necessitates the use of high specific absorption rate (SAR)‐demanding adiabatic RF pulses, limiting the signal‐to‐noise ratio (SNR) per unit of time. Here, we demonstrate the feasibility of using a body‐sized volume RF coil at 7 T, which enables uniform excitation and ultrafast power calibration by pick‐up probes. The performance of the body coil is examined by bench tests, and phantom and in vivo measurements in a 7‐T MRI scanner. The accuracy of power calibration with pick‐up probes is analyzed at a clinical 3‐T MR system with a close to identical ¹H body coil integrated at the MR system. Finally, we demonstrate high‐quality three‐dimensional ³¹P MRSI of the human body at 7 T within 5 min of data acquisition that includes RF power calibration. Copyright © 2016 John Wiley & Sons, Ltd.     

Development of the Audiometer and Audiometry

The authors consider the reasons why the induction coil audiometer was not widely adopted in clinical practise. The conclusion is that they offered little relevance to the management of hearing-impaired patients at that time, bearing in mind the state of therapeutics, surgery and contemporary aids to hearing.     

Structural diversity of coiled coils in protein fibers of the bacterial cell envelope

The cell envelope of bacteria shows great diversity in architecture and composition, to a large extent due to its proteome. Proteins localized to the cell envelope, whether integrally embedded in the membrane, membrane-anchored, or peripherally associated as part of a macromolecular complex, often form elongated fibers, in which coiled coils represent a prominent structural element. These coiled-coil segments show a surprising degree of structural variability, despite being shaped by a small number of simple biophysical rules, foremost being their geometry of interaction referred to as 'knobs-into-holes'. Here we will review this diversity, particularly as it has emerged over the last decade.