Recombinant Long-Acting Thioredoxin Ameliorates AKI to CKD Transition via Modulating Renal Oxidative Stress and Inflammation

An effective strategy is highly desirable for preventing acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Thioredoxin-1 (Trx), a redox-active protein that has anti-oxidative and anti-inflammatory properties, would be a candidate for this but its short half-life limits its clinical application. In this study, we examined the renoprotective effect of long-acting Trx that is comprised of human albumin and Trx (HSA-Trx) against AKI to CKD transition. AKI to CKD mice were created by renal ischemia-reperfusion (IR). From day 1 to day 14 after renal IR, the recovery of renal function was accelerated by HSA-Trx administration. On day 14, HSA-Trx reduced renal fibrosis compared with PBS treatment. At the early phase of fibrogenesis (day 7), HSA-Trx treatment suppressed renal oxidative stress, pro-inflammatory cytokine production and macrophage infiltration, thus ameliorating tubular injury and fibrosis. In addition, HSA-Trx treatment inhibited G2/M cell cycle arrest and apoptosis in renal tubular cells. While renal Trx protein levels were decreased after renal IR, the levels were recovered by HSA-Trx treatment. Together, HSA-Trx has potential for use in the treatment of AKI to CKD transition via its effects of modulating oxidative stress and inflammation.     

Development of fabrication process for Ag/polydiacetylene (core/shell) hybridized nanocrystals

Core/shell hybridized nanocrystals composed of Ag nanoparticle core and polydiacetylene shell were fabricated successfully by means of “co-reprecipitation/microwave irradiation method”. The hybridized nanocrystals were characterized using transmission electron microscopy (TEM) observation and UV–vis absorption spectroscopy. UV–vis spectral measurements revealed that polydiacetylene shell was the red phase while π-conjugated backbone is distorted. Detailed mechanism of formation of the red phase was discussed.     

Oxidative Stress and Its Significant Roles in Neurodegenerative Diseases and Cancer

Reactive oxygen and nitrogen species have been implicated in diverse pathophysiological conditions, including inflammation, neurodegenerative diseases and cancer. Accumulating evidence indicates that oxidative damage to biomolecules including lipids, proteins and DNA, contributes to these diseases. Previous studies suggest roles of lipid peroxidation and oxysterols in the development of neurodegenerative diseases and inflammation-related cancer. Our recent studies identifying and characterizing carbonylated proteins reveal oxidative damage to heat shock proteins in neurodegenerative disease models and inflammation-related cancer, suggesting dysfunction in their antioxidative properties. In neurodegenerative diseases, DNA damage may not only play a role in the induction of apoptosis, but also may inhibit cellular division via telomere shortening. Immunohistochemical analyses showed co-localization of oxidative/nitrative DNA lesions and stemness markers in the cells of inflammation-related cancers. Here, we review oxidative stress and its significant roles in neurodegenerative diseases and cancer.     

Acetic Acid-Catalyzed Formation of N-Phenylphthalimide from Phthalanilic Acid: A Computational Study of the Mechanism

In glacial acetic acid, phthalanilic acid and its monosubstituents are known to be converted to the corresponding phthalimides in relatively good yields. In this study, we computationally investigated the experimentally proposed two-step (addition-elimination or cyclization-dehydration) mechanism at the second-order Møller-Plesset perturbation (MP2) level of theory for the unsubstituted phthalanilic acid, with an explicit acetic acid molecule included in the calculations. In the first step, a gem-diol tetrahedral intermediate is formed by the nucleophilic attack of the amide nitrogen. The second step is dehydration of the intermediate to give N-phenylphthalimide. In agreement with experimental findings, the second step has been shown to be rate-determining. Most importantly, both of the steps are catalyzed by an acetic acid molecule, which acts both as proton donor and acceptor. The present findings, along with those from our previous studies, suggest that acetic acid and other carboxylic acids (in their undissociated forms) can catalyze intramolecular nucleophilic attacks by amide nitrogens and breakdown of the resulting tetrahedral intermediates, acting simultaneously as proton donor and acceptor. In other words, double proton transfers involving a carboxylic acid molecule can be part of an extensive bond reorganization process from cyclic hydrogen-bonded complexes.     

CuI and H2O2 Inactivate and FeII Inhibits [Fe]‐Hydrogenase at Very Low Concentrations

[Fe]‐Hydrogenase (Hmd) catalyzes reversible hydride transfer from H₂. It harbors an iron‐guanylylpyridinol as a cofactor with an Fe^II that is ligated to one thiolate, two COs, one acyl‐C, one pyridinol‐N, and solvent. Here, we report that Cu^I and H₂O₂ inactivate Hmd (half‐maximal rates at 1 μM Cu^I and 20 μM H₂O₂) and that Fe^II inhibits the enzyme with very high affinity (K_i=40 nM ). Infrared and EPR studies together with competitive inhibition studies with isocyanide indicated that Cu^I exerts its inhibitory effect most probably by binding to the active site iron‐thiolate ligand. Using the same methods, it was found that H₂O₂ binds to the active‐site iron at the solvent‐binding site and oxidizes Fe^II to Fe^III. Also it was shown that Fe^II reversibly binds away from the active site iron, with binding being competitive to the organic hydride acceptor; this inhibition is specific for Fe^II and is reminiscent of that for the [FeFe]‐hydrogenase second iron, which specifically interacts with H₂.     

Pressure-sensitive molecular film for investigation of micro gas flows

For the development of micro- and nano-technology, it has been strongly desired to understand thermo-fluid phenomena inside or around micro- and nano-devices. An optical measurement technique based on the absorption and the emission of photons by molecules is useful for experimental analyses of thermo-fluid phenomena of micro and nanoflows. The pressure-sensitive paint (PSP) technique is a potential diagnostic tool for pressure measurements of micro/nano gas flows because it works as a so-called “molecular sensor”. However, the micro-scale measurement of PSP has been limited by the aggregation of the luminescent molecules and their thick film due to the use of a polymer binder. In our previous work, we adopted the Langmuir–Blodgett (LB) technique to fabricate pressure-sensitive molecular film (PSMF) with ordered molecular assemblies, and investigated properties of PSMF. In this study, a novel approach to enhance the luminescent intensity of PSMF is proposed, and the pressure distribution in a micro-nozzle is successfully measured by using PSMF. Moreover, we compared the pressure distribution measured by PSMF with that numerically analyzed by the direct simulation monte carlo (DSMC) method, showing good agreement with each other.     

Technical note Development of a new technique for geological investigation using DTM data: An example in western Turkey

The topographic features formed by factors such as altitude, tectonic movement, lithology and others were analysed quantitatively by a new technique in this study on rift valleys in western Turkey. This technique calls for the determination of the altitude and vertical geologic movements in long-wavelength components after the separation of the short- and long-wavelength components of the two-dimensional Fast Fourier Transform (FFT) based on a digital terrain model (DTM). The location of active faults can be inferred from the magnitude of the anomalies of altitudinal dispersion and the position of the anomalies, and it is also inferred that the values of the anomalies are related to the displacement of the faults. The results have been checked in the field and it was shown that this technique is very effective for structural analysis.     

A system for synchronizing the nods of a CG character and a human using thermal image processing and a moving-average model

The purpose of this study was to develop a system for communication between a human and a computer generated (CG) character to make him or her more peaceful and cheerful. Nonverbal communication using such things as facial expression, a nod, or a hand gesture is very important for reciprocal communication between humans. In this study, an image registered by infrared rays which describes the thermal distribution of the face and neck has been used to develop a system for communication between a human and a CG character. The CG character can synchronize its nod with a person’s nod by predicting his or her nod angle. The measured feature parameter is input to a fuzzy algorithm system to obtain the nod angle of a person in front of an infrared camera, and then a moving-average model is used to predict the nod angle of the person. The average error of the nod angle obtained by the system has been estimated as about 5°. The CG character nods its head, not only when the human nods his or her head, but also when the human shakes his or her head to the left or right.