Damped Oscillating Phosphoryl Transfer Reaction in the Cyanobacterial Circadian Clock

Most organisms have circadian clocks to ensure the metabolic cycle to resonate with the rhythmic environmental changes without “damping,” or losing robustness. Cyanobacteria is the oldest and simplest form of life that is known to harbor this biological intricacy. Its KaiABC-based central oscillator proteins can be reconstituted inside a test tube, and the post-translational modification cycle occurs with 24 h periodicity. KaiC’s two major phosphorylation sites, Ser-431 and Thr-432, become phosphorylated and dephosphorylated by interacting with KaiA and KaiB, respectively. Here, we mutate Thr-432 into Ser to find the oscillatory phosphoryl transfer reaction damps. Previously, this mutant KaiC was reported to be arrhythmic in vivo. However, we found that the mutant KaiC gradually loses the ability to run in an autonomous manner and stays constitutively phosphorylated after 3 cycles in vitro

Wetting Behavior of Dental Implants

Titanium (Ti) and titanium alloys are widely used in biomedical devices and components, because of their desirable properties, such as relatively low modulus, good fatigue strength, formability, machinability, corrosion resistance, and biocompatibility. However, Ti and its alloys cannot meet all of the clinical requirements. Therefore, surface modification of Ti has been often performed to improve the biological, chemical, and mechanical properties. Various modifications of surface properties have been investigated to predictably improve the osseointegration of Ti implants. The rate and quality of osseointegration in Ti implants are related to their surface properties. A multiplicity of implant surface forms exist engineered with mechanical features that physically interlock the implant with bone. Various strategies have been utilized to improve bone integration of Ti-based implants. For example, surface grit blasting, acid-etching and anodization methods enhance cell growth, improving implant fixation through increases in interlocking surface area and alterations of oxide thickness. On the other hand, surface composition and hydrophilicity are parameters that may play a role in implant-tissue interaction and osseointegration. Highly hydrophilic surfaces seem more desirable than hydrophobic ones in view of their interactions with biological fluids, cells and tissues. Several recent studies have shown that the surface energy of biomaterials strongly has influence the initial cell attachment and spreading of osteoblastic cells on the biomaterial surfaces. Hallab et al. said that surface energy might be a more important determinant of cell adhesion and proliferation, and might be more useful than surface roughness for generating cell adhesion and cell. It may have the influence on protein adsorption and the structural rearrangement of the proteins on the material. Therefore, understanding the relationship between surface energy and cell adhesion on different biomaterials will facilitate the design of optimized implant material surfaces and subsequently the cell attachment. Surface energy is an important parameter of the material surface. It is affected by several surface characteristics, such as chemical composition, surface charge, and microstructural topography. Many papers reported that surface energy is one of important surface characteristics parameter of modified titanium surfaces. Given the importance of surface wettability of dental implants surfaces in the achievement of osseointegration, the surface free energy values for a given material, obtained by various methods and with use of different measuring liquids, are not consistent. Thus, we provided a review article of the surface modification on titanium surface and the surface wettability. The relationship between CAs and surface preparations was determined in this review

The Circadian Clock—A Molecular Tool for Survival in Cyanobacteria

Cyanobacteria are photosynthetic organisms that are known to be responsible for oxygenating Earth’s early atmosphere. Having evolved to ensure optimal survival in the periodic light/dark cycle on this planet, their genetic codes are packed with various tools, including a sophisticated biological timekeeping system. Among the cyanobacteria is Synechococcus elongatus PCC 7942, the simplest clock-harboring organism with a powerful genetic tool that enabled the identification of its intricate timekeeping mechanism. The three central oscillator proteins—KaiA, KaiB, and KaiC—drive the 24 h cyclic gene expression rhythm of cyanobacteria, and the “ticking” of the oscillator can be reconstituted inside a test tube just by mixing the three recombinant proteins with ATP and Mg2+. Along with its biochemical resilience, the post-translational rhythm of the oscillation can be reset through sensing oxidized quinone, a metabolite that becomes abundant at the onset of darkness. In addition, the output components pick up the information from the central oscillator, tuning the physiological and behavioral patterns and enabling the organism to better cope with the cyclic environmental conditions. In this review, we highlight our understanding of the cyanobacterial circadian clock and discuss how it functions as a molecular chronometer that readies the host for predictable changes in its surroundings

Shift in Conformational Equilibrium Underlies the Oscillatory Phosphoryl Transfer Reaction in the Circadian Clock

Oscillatory phosphorylation/dephosphorylation can be commonly found in a biological system as a means of signal transduction though its pivotal presence in the workings of circadian clocks has drawn significant interest: for example in a significant portion of the physiology of Synechococcus elongatus PCC 7942. The biological oscillatory reaction in the cyanobacterial circadian clock can be visualized through its reconstitution in a test tube by mixing three proteins—KaiA, KaiB and KaiC—with adenosine triphosphate and magnesium ions. Surprisingly, the oscillatory phosphorylation/dephosphorylation of the hexameric KaiC takes place spontaneously and almost indefinitely in a test tube as long as ATP is present. This autonomous post-translational modification is tightly regulated by the conformational change of the C-terminal peptide of KaiC called the “A-loop” between the exposed and the buried states, a process induced by the time-course binding events of KaiA and KaiB to KaiC. There are three putative hydrogen-bond forming residues of the A-loop that are important for stabilizing its buried conformation. Substituting the residues with alanine enabled us to observe KaiB’s role in dephosphorylating hyperphosphorylated KaiC, independent of KaiA’s effect. We found a novel role of KaiB that its binding to KaiC induces the A-loop toward its buried conformation, which in turn activates the autodephosphorylation of KaiC. In addition to its traditional role of sequestering KaiA, KaiB’s binding contributes to the robustness of cyclic KaiC phosphorylation by inhibiting it during the dephosphorylation phase, effectively shifting the equilibrium toward the correct phase of the clock

Endoplasmic Reticulum Stress and Insulin Biosynthesis: A Review

Insulin resistance and pancreatic beta cell dysfunction are major contributors to the pathogenesis of diabetes. Various conditions play a role in the pathogenesis of pancreatic beta cell dysfunction and are correlated with endoplasmic reticulum (ER) stress. Pancreatic beta cells are susceptible to ER stress. Many studies have shown that increased ER stress induces pancreatic beta cell dysfunction and diabetes mellitus using genetic models of ER stress and by various stimuli. There are many reports indicating that ER stress plays an important role in the impairment of insulin biosynthesis, suggesting that reduction of ER stress could be a therapeutic target for diabetes. In this paper, we reviewed the relationship between ER stress and diabetes and how ER stress controls insulin biosynthesis

The Evaluation of CP-001 (a Standardized Herbal Mixture of Houttuynia cordata

In the present study, the effect of CP-001, a standardized herbal mixture of Houttuynia cordata, Rehmannia glutinosa, Betula platyphylla, and Rubus coreanus, on cytochrome P450 (CYP) enzyme-mediated drug metabolism was investigated in vitro to evaluate the potential for herb-drug interactions. CP-001 was tested at concentrations of 1, 3, 10, 30, and 100 μg/mL. A CYP-specific substrate mixture was incubated with CP-001 in human liver microsomes, and the metabolites generated by each CYP-specific metabolic reaction were measured by liquid chromatography-tandem mass spectrometry. CP-001 seemed to slightly inhibit some CYP isozymes, but the IC50 values for all CYP isozymes were greater than 100 μg/mL. Furthermore, CP-001 did not exhibit time-dependent CYP inhibitory activities, indicating that it does not act as a mechanism-based inactivator of CYP enzymes. In conclusion, the effects of CP-001 on CYP isozyme activities were negligible at the concentrations tested. Therefore, the likelihood of herbal mixture-drug interaction is considered minimal

Smartphone dependence classification using tensor factorization

Excessive smartphone use causes personal and social problems. To address this issue, we sought to derive usage patterns that were directly correlated with smartphone dependence based on usage data. This study attempted to classify smartphone dependence using a data-driven prediction algorithm. We developed a mobile application to collect smartphone usage data. A total of 41,683 logs of 48 smartphone users were collected from March 8, 2015, to January 8, 2016. The participants were classified into the control group (SUC) or the addiction group (SUD) using the Korean Smartphone Addiction Proneness Scale for Adults (S-Scale) and a face-to-face offline interview by a psychiatrist and a clinical psychologist (SUC = 23 and SUD = 25). We derived usage patterns using tensor factorization and found the following six optimal usage patterns: 1) social networking services (SNS) during daytime, 2) web surfing, 3) SNS at night, 4) mobile shopping, 5) entertainment, and 6) gaming at night. The membership vectors of the six patterns obtained a significantly better prediction performance than the raw data. For all patterns, the usage times of the SUD were much longer than those of the SUC. From our findings, we concluded that usage patterns and membership vectors were effective tools to assess and predict smartphone dependence and could provide an intervention guideline to predict and treat smartphone dependence based on usage data.112Ysciescopu