Activity

We can then visualize how the molecule behaves in response to external stimulation. Since luminescence is a physical phenomenon, we can extract various kinds of information by making full use of its characteristics.Cruising inside cells in a supermicro corps, gliding down in a microtubule like a roller coaster, pushing our ways through a jungle of chromatin while hoisting a flag of nuclear localization signal — we are reminded to retain a playful and adventurous perspective at all times. What matters is mobilizing all capabilities of science and giving full play to our imagination. We believe that such serendipitous findings can arise out of such a sportive mind, a frame of mind that prevails when enjoying whale-watching.The recent advent of methods for high-throughput single-cell and spatial profiling have opened the way to complete the 150-year-old endeavor of identifying all cell types in the human body, by their distinctive molecular profiles, and to relate this information to other cellular descriptions, physiological phenotypes, molecular mechanisms and functions. Our effort to build a comprehensive reference map of the molecular state of cells in healthy human tissues is propelling the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, provides a framework for understanding cellular dysregulation in human disease, and suggests the possibility of predicting cell types and behaviors, towards a “periodic table of our cells”. In this talk, I describe our foundational work underlying single cell genomics and the conceptual framework and impact of our understanding of cell and tissue biology in health, as well as how we use it to shed light on rare disease, cancer, and COVID-19.There has been little information about the role of histamine on the central nervous system (CNS), different from dopamine and serotonin. In the present study, therefore, the effects of histamine and related compounds on the CNS were studied using rats. Intracerebroventricular (i.c.v.) injection of histamine and 2-methylhistamine ameliorated memory deficit after long interrution of learning in active avoidance response. First generation H1-antagonists inhibited active avoidance response, whereas newly develpoed H1-antagonists showed little effect. α-Fluoromethylhistidine, an histidine decarboxylase inhibitor, also inhibited active avoidance response. In radial maze performance, almost the same findings were obtained. I.c.v. injection of histamine and H1-agonists inhibited amygdaloid kindled seizures. First generation H1-antagonists attenuated histamine-induced inhibition of amygdaloid kindled seizures. Both i.c.v. and intraperitoneal injections of H3-antagonist, thioperamide, resulted in a dose-related inhibition of amygdaloid kindled seizures. The effect of thioperamide was inhibited by an H3-agonists and H1-antagonists. Similar to nitrazepam, diphenhydramine and chlorpheniramine caused a shortening of sleep latency. On the other hand, no significant effects were observed with second generation H1-antagonists. These findings suggest that histamine plays an important role in learning and memory via H1-receptors, an inhibition of amygdaloid kindled seizures induced by histamine occurred through not only H1-receptors but also H3-receptors, and that classic H1-antagonists can be useful as a effective hypnotic for difficulty in falling asleep.Target molecules of existing anti-cancer therapeutic monoclonal antibodies (mAbs) are divided into 1) receptor-type tyrosine kinases, such as human epidermal growth factor receptor (HER) family, 2) differentiation antigens, such as CD20 (Rituxan target), 3) angiogenesis-related molecules, and 4) immune checkpoint molecules (PD-1, etc.). We have recently reported a novel therapy targeting lymphangiogenesis, but not angiogenesis, using an anti-LYVE-1 (lymphatic vessel endothelial hyaluronan receptor 1) mAb. At present, many transporters are not considered to be target molecules for the cancer therapy; however, our study strongly suggested that the inhibition of cancer metabolism by mAbs against amino acid transporters will play a significant role in future cancer therapies. Most anti-cancer therapeutic mAbs bind cell-surface molecules on viable cancer cells therefore, it is necessary to produce mAbs recognizing epitopes on the extracellular domains of native and non-denatured proteins. We concluded that viable cancer cells or cells transfected with cDNA encoding target proteins are suitable immunogens for the production of anti-cancer therapeutic mAbs. We introduce our efforts to develop seeds for therapeutic mAbs using whole cancer cells and transfectants as the immunogen. selleck kinase inhibitor As many target candidates in the future are multi-pass membrane proteins, such as 12-pass amino acid transporter proteins belonging to the solute carrier (SLC) family, and their possible immunogenic extracellular regions are small, the production of specific mAbs is highly difficult. In this review, we summarize the successful preparation and characterization of mAbs recognizing the extracellular domain of oncoproteins, including transporters.In the 1980s, the authors developed the enzyme immunoassay (EIA) system for mouse nerve growth factor (NGF) to clarify its important physiological roles. Our EIA system was a new and powerful tool for measurement of extremely low levels of NGF in vitro and in vivo, and it contributed to investigation into the regulatory mechanism of NGF synthesis. After that, we demonstrated that the compounds with a low molecular weight, such as 4-methylcatechol, which elicit stimulatory activity toward NGF synthesis, were useful and practical for therapeutic purposes; as NGF has potent activity on neuronal degeneration in both the central nervous system (CNS) and the peripheral nervous system. Since 2008, we have been searching for and isolating neuroprotective component(s) from citrus peels. As a result, our study revealed that 1) 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF) has neuroprotective ability in the CNS by inducing brain-derived neurotrophic factor (BDNF) and by suppressing inflammation; 2) auraptene (AUR) also has neuroprotective ability in the CNS by suppressing inflammation and by probably inducing neurotrophic factor(s).