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The functional efficacy of colocalized, linked protein domains is dependent on linker flexibility and system compaction. However, the detailed characterization of these properties in aqueous solution presents an enduring challenge. Here, we employ a novel, to our knowledge, combination of complementary techniques, including small-angle neutron scattering, neutron spin-echo spectroscopy, and all-atom molecular dynamics and coarse-grained simulation, to identify and characterize in detail the structure and dynamics of a compact form of mercuric ion reductase (MerA), an enzyme central to bacterial mercury resistance. MerA possesses metallochaperone-like N-terminal domains (NmerA) tethered to its catalytic core domain by linkers. The NmerA domains are found to interact principally through electrostatic interactions with the core, leashed by the linkers so as to subdiffuse on the surface over an area close to the core C-terminal Hg(II)-binding cysteines. How this compact, dynamical arrangement may facilitate delivery of Hg(II) from NmerA to the core domain is discussed.  相似文献   
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Background

Despite being considered the standard surgical procedure for symptomatic cervical disc disease, anterior cervical decompression and fusion invariably accelerates adjacent segment degeneration. Cervical total disc replacement is a motion-preserving procedure developed as a substitute to fusion. Whether cervical total disc replacement is superior to fusion remains unclear.

Methods

We comprehensively searched PubMed, EMBASE, Medline, and the Cochrane Library in accordance with the inclusion criteria to identify possible studies. The retrieved results were last updated on December 12, 2014. We classified the studies as short-term and midterm follow-up.

Results

Nineteen randomized controlled trials involving 4516 cases were identified. Compared with anterior cervical decompression and fusion, cervical total disc replacement had better functional outcomes (neck disability index [NDI], NDI success, neurological success, neck pain scores reported on a numerical rating scale [NRS], visual analog scales scores and overall success), greater segmental motion at the index level, fewer adverse events and fewer secondary surgical procedures at the index and adjacent levels in short-term follow-up (P < 0.05). With midterm follow-up, the cervical total disc replacement group indicated superiority in the NDI, neurological success, pain assessment (NRS), and secondary surgical procedures at the index level (P < 0.05). The Short Form 36 (SF-36) and segmental motion at the adjacent level in the short-term follow-up showed no significant difference between the two procedures, as did the secondary surgical procedure rates at the adjacent level with midterm follow-up (P > 0.05).

Conclusions

Cervical total disc replacement presented favorable functional outcomes, fewer adverse events, and fewer secondary surgical procedures. The efficacy and safety of cervical total disc replacement are superior to those of fusion. Longer-term, multicenter studies are required for a better evaluation of the long-term efficacy and safety of the two procedures.  相似文献   
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Fluid-structural coupling occurs when microcantilever sensors vibrate in a fluid. Due to the complexity of the mechanical characteristics of microcantilevers and lack of high-precision microscopic mechanical testing instruments, effective methods for studying the fluid-structural coupling of microcantilevers are lacking, especially for non-rectangular microcantilevers. Here, we report fluid-structure interactions (FSI) of the cable-membrane structure via a macroscopic study. The simplified aeroelastic model was introduced into the microscopic field to establish a fluid-structure coupling vibration model for microcantilever sensors. We used the finite element method to solve the coupled FSI system. Based on the simplified aeroelastic model, simulation analysis of the effects of the air environment on the vibration of the commonly used rectangular microcantilever was also performed. The obtained results are consistent with the literature. The proposed model can also be applied to the auxiliary design of rectangular and non-rectangular sensors used in fluid environments.  相似文献   
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The interferon-inducible transmembrane (IFITM) proteins inhibit a wide range of viruses. We previously reported the inhibition of human immunodeficiency virus type 1 (HIV-1) strain BH10 by human IFITM1, 2 and 3. It is unknown whether other HIV-1 strains are similarly inhibited by IFITMs and whether there exists viral countermeasure to overcome IFITM inhibition. We report here that the HIV-1 NL4-3 strain (HIV-1NL4-3) is not restricted by IFITM1 and its viral envelope glycoprotein is partly responsible for this insensitivity. However, HIV-1NL4-3 is profoundly inhibited by an IFITM1 mutant, known as Δ(117–125), which is deleted of 9 amino acids at the C-terminus. In contrast to the wild type IFITM1, which does not affect HIV-1 entry, the Δ(117–125) mutant diminishes HIV-1NL4-3 entry by 3-fold. This inhibition correlates with the predominant localization of Δ(117–125) to the plasma membrane where HIV-1 entry occurs. In spite of strong conservation of IFITM1 among most species, mouse IFITM1 is 19 amino acids shorter at its C-terminus as compared to human IFITM1 and, like the human IFITM1 mutant Δ(117–125), mouse IFITM1 also inhibits HIV-1 entry. This is the first report illustrating the role of viral envelope protein in overcoming IFITM1 restriction. The results also demonstrate the importance of the C-terminal region of IFITM1 in modulating the antiviral function through controlling protein subcellular localization.  相似文献   
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