The ambient seismic wave field, also known as ambient noise, is excited by oceanic gravity waves primarily. This can be categorized as seismic hum (1–20 mHz), primary microseisms (0.02–0.1 Hz), and secondary microseisms (0.1–1 Hz). Below 20 mHz, pressure fluctuations of ocean infragravity waves reach the abyssal floor. Topographic coupling between seismic waves and ocean infragravity waves at the abyssal floor can explain the observed shear traction sources. Below 5 mHz, atmospheric disturbances may also contribute to this excitation. Excitation of primary microseisms can be attributed to topographic coupling between ocean swell and seismic waves on subtle undulation of continental shelves. Excitation of secondary microseisms can be attributed to non-linear forcing by standing ocean swell at the sea surface in both pelagic and coastal regions. Recent developments in source location based on body-wave microseisms enable us to estimate forcing quantitatively. For a comprehensive understanding, we must consider the solid Earth, the ocean, and the atmosphere as a coupled system.
Favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is an anti-viral agent that selectively and potently inhibits the RNA-dependent RNA polymerase (RdRp) of RNA viruses. Favipiravir was discovered through screening chemical library for anti-viral activity against the influenza virus by Toyama Chemical Co., Ltd. Favipiravir undergoes an intracellular phosphoribosylation to be an active form, favipiravir-RTP (favipiravir ribofuranosyl-5′-triphosphate), which is recognized as a substrate by RdRp, and inhibits the RNA polymerase activity. Since the catalytic domain of RdRp is conserved among various types of RNA viruses, this mechanism of action underpins a broader spectrum of anti-viral activities of favipiravir. Favipiravir is effective against a wide range of types and subtypes of influenza viruses, including strains resistant to existing anti-influenza drugs. Of note is that favipiravir shows anti-viral activities against other RNA viruses such as arenaviruses, bunyaviruses and filoviruses, all of which are known to cause fatal hemorrhagic fever. These unique anti-viral profiles will make favipiravir a potentially promising drug for specifically untreatable RNA viral infections.
Transient Receptor Potential (TRP) proteins form cation channels characterized by a wide variety of activation triggers. Here, we overview a group of TRP channels that respond to reactive redox species to transduce physiological signals, with a focus on TRPA1 and its role in oxygen physiology. Our systematic evaluation of oxidation sensitivity using cysteine-selective reactive disulphides with different redox potentials reveals that TRPA1 has the highest sensitivity to oxidants/electrophiles among the TRP channels, which enables it to sense O2. Proline hydroxylation by O2-dependent hydroxylases also regulates the O2-sensing function by inhibiting TRPA1 in normoxia; TRPA1 is activated by hypoxia through relief from the inhibition and by hyperoxia through cysteine oxidation that overrides the inhibition. TRPA1 enhances neuronal discharges induced by hyperoxia and hypoxia in the vagus to underlie respiratory adaptation to changes in O2 availability. This importance of TRPA1 in non-carotid body O2 sensors can be extended to the universal significance of redox-sensitive TRP channels in O2 adaptation.
One of the most fundamental questions in neurobiology is how proper synaptic connections are established in the developing brain. Live-cell imaging of the synaptic structure and functional molecules can reveal the time course of synapse formation, molecular dynamics, and functional maturation. Using postsynaptic scaffolding proteins as a marker of synapse development, fluorescence time-lapse imaging revealed rapid formation of individual synapses that occurred within hours and their remodeling in culture preparations. In vivo two-photon excitation microscopy development enabled us to directly measure synapse turnover in living animals. In vivo synapse dynamics were suppressed in the adult rodent brain, but were maintained at a high level during the early postnatal period. This transition in synapse dynamics is biologically important and can be linked to the pathology of juvenile-onset psychiatric diseases. Indeed, the upregulation of synapse dynamics was observed in multiple mouse models of autism spectrum disorders. Fluorescence imaging of synapses provides new information regarding the physiology and pathology of neural circuit construction.
Estrogen receptors (ER) are important transcription factors to relay signals from estrogen and to regulate proliferation of some of breast cancers. The cycling of estrogen-induced DNA binding and ubiquitin-linked proteolysis of ER potentiates ER-mediated transcription. Indeed, several transcriptional coactivators for ER-dependent transcription ubiquitinate ER. Histone acetyltransferase (HAT) Hbo1/KAT7/MYST2, involved in global histone acetylation, DNA replication, transcription, and cellular proliferation, promotes proteasome-dependent degradation of ERα through ubiquitination. However, molecular mechanism for ubiquitination of ERα by Hbo1 is unknown. Here we report the intrinsic ubiquitin E3 ligase activity of Hbo1 toward the ERα. The ligand, estradiol-17β, inhibited E3 ligase activity of Hbo1 for ERα in vitro, whereas hyperactive ERα mutants from metastatic breast cancers resistant to hormonal therapy, were better substrates for ERα ubiquitination by Hbo1. Hbo1 knock-down caused increase in ERα expression. Hbo1 is another ERα coactivator that ubiquitinates ERα.
Our previous functional magnetic resonance imaging (fMRI) studies have indicated that the left dorsal inferior frontal gyrus (L. dF3op/F3t) and left lateral premotor cortex (L. LPMC) are crucial regions for syntactic processing among the syntax-related networks. In the present study, we further examined how activations in these regions were modified by the factors of construction and scrambling (object-initial type). Using various sentence types, we clarified three major points. First, we found that the main effects of construction and scrambling consistently activated the L. dF3op/F3t and L. LPMC. Secondly, the main effects of scrambling clearly localized activation in the L. dF3op/F3t and L. LPMC, indicating the more narrowed down processing of syntax. Thirdly, step-wise percent signal changes were observed in the L. dF3op/F3t, demonstrating synergistic effects of construction and scrambling. These results demonstrate the abstract and intensive nature of syntactic processing carried out by these regions, i.e., the grammar center.