Several phenomena occurring throughout the life of living things start and end with proteins. Various proteins form one complex structure to control detailed reactions. In contrast, one protein forms various structures and implements other biological phenomena depending on the situation. The basic principle that forms these hierarchical structures is protein self-assembly. A single building block is sufficient to create homogeneous structures with complex shapes, such as rings, filaments, or containers. These assemblies are widely used in biology as they enable multivalent binding, ultra-sensitive regulation, and compartmentalization. Moreover, with advances in the computational design of protein folding and protein–protein interfaces, considerable progress has recently been made in the de novo design of protein assemblies. Our review presents a description of the components of supramolecular protein assembly and their application in understanding biological phenomena to therapeutics.

Objective The aim of this study was to evaluate the amount of tooth movement and histologic changes with different corticotomy designs and micro-osteoperforation in rabbits. Methods The sample consisted of 24 rabbits divided into three experimental groups (triangular corticotomy [TC] and indentation corticotomy [IC] with flap, and flapless micro-osteoperforations [MP]) and a control. A traction force of 100 cN was applied by connecting the first premolars to the incisors. The amount of tooth movement was measured. Kruskal-Wallis test was used to assess differences in tooth movement between the groups. Micro-computed tomography, hematoxylin and eosin staining, and tartrate-resistant acidic phosphatase (TRAP) analysis were performed. Analysis of variance was applied to assess differences in TRAP-positive osteoclast count between the groups. Results The amount of tooth movement increased by 46.5% and 32.0% in the IC and MP groups, respectively, while the bone fraction analysis showed 69.7% and 8.5% less mineralization compared to the control. There were no significant intergroup differences in the number of TRAP-positive osteoclasts. Conclusions The micro-osteoperforation group showed no significant differences in the amount of tooth movement compared to the corticotomy groups, nor in the TRAP-positive osteoclast count compared to both corticotomy groups and control.

BackgroundRecently, the metabolite-likeness of the drug space has emerged and has opened a new possibility for exploring human metabolite-like candidates in drug discovery. However, the applicability of metabolite-likeness in drug discovery has been largely unexplored. Moreover, there are no reports on its applications for the repositioning of drugs to possible enzyme modulators, although enzyme-drug relations could be directly inferred from the similarity relationships between enzyme’s metabolites and drugs.MethodsWe constructed a drug-metabolite structural similarity matrix, which contains 1,861 FDA-approved drugs and 1,110 human intermediary metabolites scored with the Tanimoto similarity. To verify the metabolite-likeness measure for drug repositioning, we analyzed 17 known antimetabolite drugs that resemble the innate metabolites of their eleven target enzymes as the gold standard positives. Highly scored drugs were selected as possible modulators of enzymes for their corresponding metabolites. Then, we assessed the performance of metabolite-likeness with a receiver operating characteristic analysis and compared it with other drug-target prediction methods. We set the similarity threshold for drug repositioning candidates of new enzyme modulators based on maximization of the Youden’s index. We also carried out literature surveys for supporting the drug repositioning results based on the metabolite-likeness.ResultsIn this paper, we applied metabolite-likeness to repurpose FDA-approved drugs to disease-associated enzyme modulators that resemble human innate metabolites. All antimetabolite drugs were mapped with their known 11 target enzymes with statistically significant similarity values to the corresponding metabolites. The comparison with other drug-target prediction methods showed the higher performance of metabolite-likeness for predicting enzyme modulators. After that, the drugs scored higher than similarity score of 0.654 were selected as possible modulators of enzymes for their corresponding metabolites. In addition, we showed that drug repositioning results of 10 enzymes were concordant with the literature evidence.ConclusionsThis study introduced a method to predict the repositioning of known drugs to possible modulators of disease associated enzymes using human metabolite-likeness. We demonstrated that this approach works correctly with known antimetabolite drugs and showed that the proposed method has better performance compared to other drug target prediction methods in terms of enzyme modulators prediction. This study as a proof-of-concept showed how to apply metabolite-likeness to drug repositioning as well as potential in further expansion as we acquire more disease associated metabolite-target protein relations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-017-1637-5) contains supplementary material, which is available to authorized users.

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A transient cytosolic delivery system for accurate Cas9 ribonucleoprotein is a key factor for target specificity of the CRIPSR/Cas9 toolkit. Owing to the large size of the Cas9 protein and a long negative strand RNA, the development of the delivery system is still a major challenge. Here, a size‐controlled lipopeptide‐based nanosome system is reported, derived from the blood‐brain barrier‐permeable dNP2 peptide which is capable of delivering a hyperaccurate Cas9 ribonucleoprotein complex (HypaRNP) into human cells for gene editing. Each nanosome is capable of encapsulating and delivering ≈2 HypaRNP molecules into the cytoplasm, followed by nuclear localization at 4 h post‐treatment without significant cytotoxicity. The HypaRNP thus efficiently enacts endogenous eGFP silencing and editing in human embryonic kidney cells (up to 27.6%) and glioblastoma (up to 19.7% frequency of modification). The lipopeptide‐based nanosome system shows superior delivery efficiency, high controllability, and simplicity, thus providing biocompatibility and versatile platform approach for CRISPR‐mediated transient gene editing applications.

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A via reliability test of PCB board using embedded MLCC was evaluated by HALT and Pressure Cooker Test PCT. The reliability of HALT was evaluated at 125 ℃ , 4Vr, and 12Hr. The purpose of this test was to verify the stability of the MLCC by predicting the lifetime of the PCB. The PCBT conditions were measured at 85% humidity and 2 atm, and the reliability of the PCBs under severe conditions than HALT was evaluated. The basic characteristics of MLCC size are 0603 (600x300um), Capacitance 100nF, thickness 150µm. The initial electrical characteristics of the MLCC were measured at a rated voltage (10V) with a capacitance value of 98 ~ 103nF, a loss rate of 0.048%, and an insulation resistance of 1.08 x10 10 (Ω). The HALT test results showed that all the measured samples showed a value of 1x10 7 Ω or more, and passed for the HALT test. The PCBT test resulted in failure, and the first sample fell below the poor insulation resistance at the start of the PCBT test. In the case of the second sample, the insulation resistance dropped to less than the defective insulation resistance for more than 30 hours, and the third sample has an appropriate insulation resistance of 1.0x10 6 Ω even for more than 60 hours. It is confirmed that there is the greatest the possibility of failure in the part between the embedded chip and via that Cu plating is performed to form via by fill plating. Therefore, it is necessary to optimize the plating thickness and size conditions because the embedded MLCC has a high probability that defects mainly occur in VIA crack or delamination

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