► Disulfide-rich peptide aptamer inhibits IL-6-dependent cell proliferation. ► Disulfide bond of peptide aptamer is essential for its affinity to IL-6R. ► Inhibitory effect of peptide depends on ...number and pattern of its disulfide bonds.
Several engineered protein scaffolds have been developed recently to circumvent particular disadvantages of antibodies such as their large size and complex composition, low stability, and high production costs. We previously identified peptide aptamers containing one or two disulfide-bonds as an alternative ligand to the interleukin-6 receptor (IL-6R). Peptide aptamers (32 amino acids in length) were screened from a random peptide library by in vitro peptide selection using the evolutionary molecular engineering method “cDNA display”. In this report, the antagonistic activity of the peptide aptamers were examined by an in vitro competition enzyme-linked immunosorbent assay (ELISA) and an IL-6-dependent cell proliferation assay. The results revealed that a disulfide-rich peptide aptamer inhibited IL-6-dependent cell proliferation with similar efficacy to an anti-IL-6R monoclonal antibody.
A 61‐year‐old man with repeated numbness of the legs since his 30s, whose father had similar symptoms, developed progressive muscle weakness, distal sensory impairment and an unstable gait. Deletion ...of the PMP22 gene was identified and he was diagnosed with hereditary neuropathy with liability to pressure palsy (HNPP). The nerve conduction study showed mixed type neuropathies, and needle‐electromyography (n‐EMG) showed positive sharp waves and fibrillation potentials, which are uncommon findings of HNPP. As severe hypothyroidism was also indicated, hormone replacement was started. The n‐EMG abnormalities and motor symptoms were remarkably improved after treatment. Hypothyroidism might be a risk factor for the worsening of neuropathies of HNPP.
Carbon nanotubes (CNTs) have already been successfully implemented in various fields, and they are anticipated to have innovative applications in medical science. However, CNTs have asbestos-like ...properties, such as their nanoscale size and high aspect ratio (>100). Moreover, CNTs may persist in the body for a long time. These properties are thought to cause malignant mesothelioma and lung cancer. However, based on conventional toxicity assessment systems, the carcinogenicity of asbestos and CNTs is unclear. The reason for late countermeasures against asbestos is that reliable, long-term safety assessments have not yet been developed by toxicologists. Therefore, a new type of long-term safety assessment, different from the existing methods, is needed for carbon nanomaterials. Recently, we applied a proteomic approach to the safety assessment of carbon nanomaterials. In this review, we discuss the basic concept of our approach, the results, the problems, and the possibility of a long-term safety assessment for carbon nanomaterials using the toxicoproteomic approach.
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Cervical Cord Injury (CCI) is a dysfunction of the upper limb. In an individual with C5-level CCI, which is the most frequent of all eight levels, force can be applied in the direction of flexion by ...the biceps brachii, but extension force cannot be applied because of the triceps brachii paralysis. Persons with C5-level CCI therefore cannot operate a wheelchair up an incline and over carpet. In this study, we estimated the wheelchair velocity during elbow flexion depending on the angular velocity of the elbow. A wearable assistive robot can assist with the elbow extension movement using this estimated velocity while the wheelchair is being operated.
Nuclear emulsion plates for studying elementary particle physics as well as cosmic ray physics are very powerful tracking tools with sub-micron spatial resolutions of charged particle trajectories. ...Even if gamma rays have to be detected, electron-positron pair tracks can provide precise information to reconstruct their direction and energy with high accuracy. Recent developments of emulsion analysis technology can digitally handle almost all tracks recorded in emulsion plates by using the Hyper Track Selector of the OPERA group at NAGOYA University. On the other hand, the potential of time resolutions have been equipped by emulsion multilayer shifter technology in the GRAINE (Gamma Ray Astro-Imager with Nuclear Emulsion) experiments, the aims of which are to detect cosmic gamma rays such as the Vela pulsar stellar object by precise emulsion tracking analysis and to study cosmic ray particle interactions and chemical compositions. In this paper, we focus on the subject of cosmic ray nuclei detection in the GRAINE balloon flight experiments launched at Alice Springs, Australia in May 2015.
Nuclear emulsion plates for studying elementary particle physics as well as cosmic ray physics are very powerful tracking tools with sub-micron spatial resolutions of charged particle trajectories. ...Even if gamma rays have to be detected, electron-positron pair tracks can provide precise information to reconstruct their direction and energy with high accuracy. Recent developments of emulsion analysis technology can digitally handle almost all tracks recorded in emulsion plates by using the Hyper Track Selector of the OPERA group at NAGOYA University. On the other hand, the potential of time resolutions have been equipped by emulsion multilayer shifter technology in the GRAINE (Gamma Ray Astro-Imager with Nuclear Emulsion) experiments, the aims of which are to detect cosmic gamma rays such as the Vela pulsar stellar object by precise emulsion tracking analysis and to study cosmic ray particle interactions and chemical compositions. In this paper, we focus on the subject of cosmic ray nuclei detection in the GRAINE balloon flight experiments launched at Alice Springs, Australia in May 2015.
Our aim was to show whether sensitivity for detecting volume changes in regional gray matter in default mode network (DMN) at converted from mild cognitive impairment to Alzheimer’s disease (from MCI ...to AD) phase was improved by use of a standardized volume with global gray-matter volume. T1-weighted MR images (T1WI) of seven normal subjects and seven converted (from MCI to AD) patients were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Gray-matter images segmented with Statistical Parametric Mapping 5 were measured by the atlas-based method. We focused on five nodes of the DMN. For each phase, region of interest (ROI) volumes in the five nodes were standardized by two methods: (1) the ratio to the screening phase (S_volume) and (2) the ratio to the screening phase after both volumes were standardized by the global gray-matter volume (S_N_volume). Significant group differences between longitudinal gray-matter volume change of the converted (from MCI to AD) group and that of the normal group were found in lateral temporal cortex by S_N_volume, and precuneus by S_N_volume. These findings are useful for improving the understanding of DMN volume changes at the converted (from MCI to AD) phase.
Small GTPase proteins, including RhoA, RhoB, RhoC, Rac1 and cdc42, are molecules that have significant roles in linking cell shape and cell cycle progression in cytoskeletal arrangements and ...mitogenic signaling. Rho GDP dissociation inhibitor 2 (RhoGDI2) has recently been identified as a metastasis suppressor gene in models of bladder cancer. RhoGDI2 has also been identified as a potential regulator of tumorigenesis and cancer progression. The present study aimed to clarify the significance of RhoGDI2 gene expression in gastric carcinoma and to evaluate the outcome of affected patients. A total of 46 pairs of normal mucosa and cancer specimens were obtained from patients who had undergone a gastrectomy for primary gastric carcinoma and were subjected to semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) for RhoGDI2. The expression of RhoGDI2 mRNA was significantly higher in early-stage gastric cancer specimens compared with the normal gastric epithelium samples. By contrast, the depth of the tumor was negatively correlated with RhoGDI2 mRNA expression. In addition, a reduced expression of RhoGDI2 mRNA was associated with venous system invasion and lymph node metastasis. RhoGDI2 mRNA was more frequently expressed in differentiated adenocarcinoma compared with poorly-differentiated adenocarcinoma. Although the statistical significance was not established, RhoGDI2-positive patients tended to have a superior oncological outcome compared with RhoGDI2-negative patients. The reduced expression of RhoGDI2 mRNA in gastric carcinoma is associated with venous system invasion and lymph node metastasis.
To reveal the nature of the photoinduced insulator-metal transition, we show that an exact analysis of the Falicov-Kimball model subject to external ac electric fields becomes possible with Floquet's ...method combined with the nonequilibrium dynamical mean-field theory. The nonequilibrium steady state that appears during irradiation of a pump light is shown to be determined if the dissipation in a certain heat-bath model is introduced. This has enabled us to predict that novel features characteristic of the photoexcited steady states, i.e., negative weight (gain) in the low-energy region and dip structures around the photon energy of the pump light, should be observed in the optical conductivity. Special emphasis is put on the role of dissipation, for which we elaborate the dependence of the steady state on the strength of dissipation and the temperature of the heat bath.
The purpose of the present paper was to investigate the effect of regular walking exercise on glucose tolerance and insulin response to i.v. glucose infusion in growing beef steers. Four crossbred ...beef steers walked on a treadmill during a 6 week exercise period (1.2 km/h, 1 h/day and 5 days/week). The changes in plasma glucose and insulin levels following glucose infusion were analyzed immediately prior to (bodyweight: 260.4+-24.2 kg) and after (295.7+-30.1 kg) the exercise period. The basal levels of plasma glucose (86.4 vs. 82.0 mg/dL, P=0.040) and insulin (24.5 vs. 14.3 microU/mL, P=0.016) were significantly lower after the exercise period. Further, the increase in the levels of plasma glucose (420.4 vs. 280.8 mg/dL, P0.001) and insulin (94.5 vs. 73.1 microU/mL. P