PKC-δ mediates interferon-α-induced apoptosis through c-Jun NH2-terminal kinase activation

<p>Abstract</p> <p>Background</p> <p>Interferon-α (IFN-α) exerts an anti-tumor effect at least through induction of apoptosis in a variety of types including B lymphoma cells. We recently found that IFN-α induced a sustained activation of c-Jun NH₂-terminal kinase1 (JNK1), which is implicated in activation of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) promoter. In the present study, we explored upstream component(s) of the prolonged IFN-α-initiated activation of JNK1.</p> <p>Results</p> <p>IFN-α caused activation of PKC-δ in Daudi B lymphoma cells and myeloma U266 cells, as detected by Western blotting using a monoclonal antibody specific for the phosphorylated form of PKC-δ. The dominant-negative form of mutant PKC-δ (dnPKC-δ) reduced the IFN-α-induced JNK1 activation, TRAIL promoter activity, loss of mitochondrial membrane potential (ΔΨm), and increase in propidium iodide (PI) positive cells. The IFN-α-induced activation of JNK1 and the TRAIL promoter was also attenuated by the PKC-δ inhibitor rottlerin. Moreover, a constitutively active form of mutant PKC-δ enhanced the IFN-α-induced TRAIL promoter activity and loss of ΔΨm in Daudi B lymphoma cells. In addition, IFN-α-induced Ser727 phosphorylation of Stat1 was also abrogated by dnPKC-δ.</p> <p>Conclusions</p> <p>IFN-α induced JNK1 activation via PKC-δ, leading to upregulation of TRAIL. The interaction of the consequent enhanced TRAIL expression with TRAIL-receptor results in a loss of ΔΨm and increase in PI positive cells. The IFN-α-induced apoptotic events may also be affected by the Ser727-Stat1 induced by PKC-δ-mediated signaling component(s).</p

A robotic vision system emulating fixational eye movements and retinal sampling

Recent studies on visual physiology have suggested that fixational eye movements contribute to the information processing function of the retina. In this study, we built a robotic vision system that emulates the characteristics of fixational eye movements and retinal sampling as an assistant tool for clarifying information processing through the collaboration of eye movements and neural circuits. The proposed robotic vision system consists of two galvanometers, a field-programmable gate array (FPGA) board, and a high-speed, high-resolution camera. We measured the frequency response of this robotic vision system, and the results showed that the system satisfied the requirements for emulating the frequency characteristics of biological eye movements. In addition, we generated command signals in the FPGA to emulate biological eye movements and confirmed the satisfactory operation of the system.The 2022 International Conference on Artificial Life and Robotics (ICAROB 2022), January 20-23, 2022, on line, Oita, Japa

Changes in intentional binding effect during a novel perceptual-motor task

Perceptual-motor learning describes the process of improving the smoothness and accuracy of movements. Intentional binding (IB) is a phenomenon whereby the length of time between performing a voluntary action and the production of a sensory outcome during perceptual-motor control is perceived as being shorter than the reality. How IB may change over the course of perceptual-motor learning, however, has not been explicitly investigated. Here, we developed a set of IB tasks during perceptual-motor learning. Participants were instructed to stop a circular moving object by key press when it reached the center of a target circle on the display screen. The distance between the center of the target circle and the center of the moving object was measured, and the error was used to approximate the perceptual-motor performance index. This task also included an additional exercise that was unrelated to the perceptual-motor task: after pressing the key, a sound was presented after a randomly chosen delay of 200, 500, or 700 ms and the participant had to estimate the delay interval. The difference between the estimated and actual delay was used as the IB value. A cluster analysis was then performed using the error values from the first and last task to group the participants based on their perceptual-motor performance. Participants showing a very small change in error value, and thus demonstrating a small effect of perceptual-motor learning, were classified into cluster 1. Those who exhibited a large decrease in error value from the first to the last set, and thus demonstrated a strong improvement in perceptual-motor performance, were classified into cluster 2. Those who exhibited perceptual-motor learning also showed improvements in the IB value. Our data suggest that IB is elevated when perceptual-motor learning occurs

An artifice in the insertion of the Hickman catheter in small children

Although the Hickman catheter is commonly used in pediatric patients, it is difficult to place this catheter safely in small children, especially infants. A multiple-step method, starting with a thinner catheter, makes the placement easier and safer.Keywords: central venous catheter, children, Hickman cathete

Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats

The RIβ subunit of cAMP-dependent protein kinase (PKA), encoded by Prkar1b, is a neuronal isoform of the type I regulatory subunit of PKA. Mice lacking the RIβ subunit exhibit normal long-term potentiation (LTP) in the Schaffer collateral pathway of the hippocampus and normal behavior in the open-field and fear conditioning tests. Here, we combined genetic, electrophysiological, and behavioral approaches to demonstrate that the RIβ subunit was involved in body tremor, LTP in the Schaffer collateral pathway, and fear conditioning memory in rats. Genetic analysis of WTC-furue, a mutant strain with spontaneous tremors, revealed a deletion in the Prkar1b gene of the WTC-furue genome. Prkar1b-deficient rats created by the CRISPR/Cas9 system exhibited body tremor. Hippocampal slices from mutant rats showed deficient LTP in the Schaffer collateral–CA1 synapse. Mutant rats also exhibited decreased freezing time following contextual and cued fear conditioning, as well as increased exploratory behavior in the open field. These findings indicate the roles of the RIβ subunit in tremor pathogenesis and contextual and cued fear memory, and suggest that the hippocampal and amygdala roles of this subunit differ between mice and rats and that rats are therefore beneficial for exploring RIβ function

A New Strategy for Surgical Intervention of Bisphosphonate-Related Osteonecrosis of the Jaw : A retrospective study.

Bisphosphonates (BPs) are now widely used to treat various skeletal complications. Although the number of reported cases ofbisphosphonate-related osteonecrosis of the jaw (BRONJ) is rapidly increasing worldwide, therapeutic strategies remain controversial.Conservative treatments including antibacterial mouth rinses, the systemic administration of antibiotics, and superficial debridement in stage II BRONJ have been recommended by the American Association of Oral and Maxillofacial Surgeons position paper. However, these treatments are only partially successful. We performed a surgical intervention that consisted of osteotomy and primary wound closure in patients with stages II and III BRONJ. Forty-three out of 44 cases were treated effectively by this strategy, leading to improvements in quality of life. All BRONJ patients treated with oral BPs were treated successfully by the surgical intervention. We also proposed a surgical intervention for patients with stage II BRONJ

Association between high psychological distress and poor oral health-related quality of life (OHQoL) in Japanese community-dwelling people: the Nagasaki Islands Study

Background: We investigated the association between psychological distress and oral health status/oral health-related quality of life (OHQoL) in Japanese community-dwelling people. Methods: We conducted a cross-sectional study using data from the Nagasaki Islands Study. A total of 1183 (455 men and 728 women)has been analyzed in this study. Psychological distress was measured using the Kessler Psychological Distress Scale (K6). Oral health status was measured by dental examination. The OHQoL was measured using the General Oral Health Assessment Index (GOHAI). We defined the total score of ?5 points on the K6 as high psychological distress (high-K6 group). Results: The multiple linear regression analysis to identify the GOHAI showed that gender, K6, the total number of teeth, the number of dental caries, and visiting a dental clinic within the past 6 months significantly associated with the GOHAI. Among all of these variables, high-K6 (? 5)was a substantial contributing factor of the GOHAI (β = ? 0.23, 95% Cl ? 2.31 to ?1.41, p < 0.0001).Conclusions: It is likely that the individual with high psychological distress was strongly related to poor OHQoL even in the general population