Applied Microbiology and Biotechnology - Short-chain carboxylic acids and their derivatives are widely utilized in all aspects of our daily life. Given their specific functional groups, these... 相似文献
Neurochemical Research - Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disease with a high mortality rate affecting individuals worldwide. After ICH, persistent inflammation... 相似文献
Resonant optical dipole nano-antennas allow giant field enhancement within nano-gaps. To show how the energy of external illumination waves is delivered and concentrated in nano-gaps, we build up a model by considering the dynamical launching and multiple scattering processes of surface plasmon polaritions (SPPs) on both antenna arms. The model captures the main feature of the antenna resonance as evidenced by comparison of the model prediction with fully vectorial numerical results and provides an intuitive picture that the energy of external wave is initially transferred into SPP and is then coupled into the nano-gap. The enhanced field in the nano-gap oscillates quasi-periodically with the increase of the antenna-arm length, and the resonance peaks can be predicted with a phase-matching condition derived from the model, showing that antenna resonance is due to a constructive interference of the multiple-scattered SPPs. Analytical equation for determining the complex resonance wavelength and the quality factor of the resonant modes is obtained. The model however exhibits observable deviation from fully vectorial numerical results for the lowest resonance order (for antenna with the shortest arms), evidencing that, for this case, surface waves other than SPPs contribute to the antenna resonance. The present results are helpful for clarifying the underlying physics for the energy concentration with resonant dipole antennas and may provide recipes for intuitive design of antenna devices, such as those used for optical nonlinearity enhancement and biochemical sensing. 相似文献
Genome-wide association studies have identified SNP rs11249433 at chromosome 1p11 as a new breast cancer (BC) susceptibility locus in populations of European descent. Since then, the relationship between 1p11- rs11249433 and breast cancer has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 15 studies involving a total of 90,154 cases and 137,238 controls for 1p11-rs11249433 polymorphism to evaluate its effect on genetic susceptibility for breast cancer. An overall random effects odds ratio of 1.09 (95% CI: 1.06-1.12, P<10-5) was found for rs11249433-G variant. Significant results were also observed for heterozygous (OR=1.09, 95% CI: 1.05-1.12, P<10-5) and homozygote (OR=1.14, 95% CI: 1.08-1.21, P<10-5). There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. After stratified by ethnicity, significant associations were found among Caucasians. However, no significant associations were detected among East Asian and African populations. In addition, we found that rs11249433 polymorphism on 1p11 confer risk, exclusively for ER-positive tumors with per-allele OR of 1.13 (95% CI: 1.08-1.18; P <10-5) compared to ER-negative tumors of 1.01 (95% CI: 0.98-1.04; P=0.49). Similar results were also observed when stratified by PR status. Our findings demonstrated that rs11249433-G allele is a risk-conferring factor for the development of breast cancer, especially in Caucasians. 相似文献
Timely and faithful duplication of the entire genome depends on completion of replication. Replication forks frequently encounter obstacles that may cause genotoxic fork stalling. Nevertheless, failure to complete replication rarely occurs under normal conditions, which is attributed to an intricate network of proteins that serves to stabilize, repair and restart stalled forks. Indeed, many of the components in this network are encoded by tumour suppressor genes, and their loss of function by mutation or deletion generates genomic instability, a hallmark of cancer. Paradoxically, the same fork‐protective network also confers resistance of cancer cells to chemotherapeutic drugs that induce high‐level replication stress. Here, we review the mechanisms and major pathways rescuing stalled replication forks, with a focus on fork stabilization preventing fork collapse. A coherent understanding of how cells protect their replication forks will not only provide insight into how cells maintain genome stability, but also unravel potential therapeutic targets for cancers refractory to conventional chemotherapies. 相似文献
With increasing concerns in sustainable development, biocatalysis has been recognized as a competitive alternative to traditional chemical routes in the past decades. As nature’s biocatalysts, enzymes are able to catalyze a broad range of chemical transformations, not only with mild reaction conditions but also with high activity and selectivity. However, the insufficient activity or enantioselectivity of natural enzymes toward non-natural substrates limits their industrial application, while directed evolution provides a potent solution to this problem, thanks to its independence on detailed knowledge about the relationship between sequence, structure, and mechanism/function of the enzymes. A proper high-throughput screening (HTS) method is the key to successful and efficient directed evolution. In recent years, huge varieties of HTS methods have been developed for rapid evaluation of mutant libraries, ranging from in vitro screening to in vivo selection, from indicator addition to multi-enzyme system construction, and from plate screening to computation- or machine-assisted screening. Recently, there is a tendency to integrate directed evolution with metabolic engineering in biosynthesis, using metabolites as HTS indicators, which implies that directed evolution has transformed from molecular engineering to process engineering. This paper aims to provide an overview of HTS methods categorized based on the reaction principles or types by summarizing related studies published in recent years including the work from our group, to discuss assay design strategies and typical examples of HTS methods, and to share our understanding on HTS method development for directed evolution of enzymes involved in specific catalytic reactions or metabolic pathways.