Synergistic Integration of Detailed Meteorological and Community Information for Evacuation from Weather-Related Disasters: Proposal of a “Disaster Response Switch”

Meteorological information used for disaster prevention has developed rapidly in terms of both type and specificity. The latest forecasting models can predict weather with very high resolutions that can characterize disaster risk at the local level. However, this development can lead to an overdependency on the information and a wait-and-see attitude by the public. At the same time, residents share and use various types of information for disaster response, such as local conditions, in addition to official disaster information. Our research in Japan verified the practicality and efficiency of synergistically integrating these types of information by examining actual evacuation cases. The current numerical forecasting models sufficiently identify locality from the viewpoint of various administrative scales such as prefectures, municipalities, and school districts, but the improvements to these models have failed to improve residents’ judgment in successful evacuation cases. We therefore analyzed the relationship between meteorological information and residents’ disaster response and confirmed that they were strongly correlated and were contributing factors in preventing disasters. We revealed differences between a community’s disaster prevention culture and the disaster information provided. This led us to propose a new concept in community disaster prevention that we call the “disaster response switch,” which can serve as a data-driven risk management tool for communities when used in combination with advanced meteorological disaster information.

Determinants of Periodontal/Periapical Lesion Stability and Progression

Periodontal and periapical lesions are infectious inflammatory osteolitytic conditions in which a complex inflammatory immune response mediates bone destruction. However, the uncertainty of a lesion’s progressive or stable phenotype complicates understanding of the cellular and molecular mechanisms triggering lesion activity. Evidence from clinical and preclinical studies of both periodontal and periapical lesions points to a high receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) ratio as the primary determinant of osteolytic activity, while a low RANKL/OPG ratio is often observed in inactive lesions. Proinflammatory cytokines directly modulate RANKL/OPG expression and consequently drive lesion progression, along with pro-osteoclastogenic support provided by Th1, Th17, and B cells. Conversely, the cooperative action between Th2 and Tregs subsets creates an anti-inflammatory and proreparative milieu associated with lesion stability. Interestingly, the trigger for lesion status switch from active to inactive can originate from an unanticipated RANKL immunoregulatory feedback, involving the induction of Tregs and a host response outcome with immunological tolerance features. In this context, dendritic cells (DCs) appear as potential determinants of host response switch, since RANKL imprint a tolerogenic phenotype in DCs, described to be involved in both Tregs and immunological tolerance generation. The tolerance state systemically and locally suppresses the development of exacerbated and pathogenic responses and contributes to lesions stability. However, immunological tolerance break by comorbidities or dysbiosis could explain lesions relapse toward activity. Therefore, this article will provide a critical review of the current knowledge concerning periodontal and periapical lesions activity and the underlying molecular mechanisms associated with the host response. Further studies are required to unravel the role of immunological responsiveness or tolerance in the determination of lesion status, as well as the potential cooperative and/or inhibitory interplay among effector cells and their impact on RANKL/OPG balance and lesion outcome.

GABA in, garbage out: AIS-located proteasomes regulate the developmental GABA switch

The GABA response switch from excitatory to inhibitory is a key event in neuronal maturation that depends on the regulated expression of chloride transporters NKCC1 and KCC2. In this issue, Lee et al. (2020. J. Cell. Biol.https://doi.org/10.1083/jcb.201903033) describe how degradation of NKCC1 by proteasomes immobilized at the axon initial segment (AIS) by the Ecm29 adaptor contributes to this regulation, driving the GABA switch and the positional maturation of the AIS.

Ecm29-mediated proteasomal distribution modulates excitatory GABA responses in the developing brain

Neuronal GABAergic responses switch from excitatory to inhibitory at an early postnatal period in rodents. The timing of this switch is controlled by intracellular Cl− concentrations, but factors determining local levels of cation-chloride cotransporters remain elusive. Here, we report that local abundance of the chloride importer NKCC1 and timely emergence of GABAergic inhibition are modulated by proteasome distribution, which is mediated through interactions of proteasomes with the adaptor Ecm29 and the axon initial segment (AIS) scaffold protein ankyrin G. Mechanistically, both the Ecm29 N-terminal domain and an intact AIS structure are required for transport and tethering of proteasomes in the AIS region. In mice, Ecm29 knockout (KO) in neurons increases the density of NKCC1 protein in the AIS region, a change that positively correlates with a delay in the GABAergic response switch. Phenotypically, Ecm29 KO mice showed increased firing frequency of action potentials at early postnatal ages and were hypersusceptible to chemically induced convulsive seizures. Finally, Ecm29 KO neurons exhibited accelerated AIS developmental positioning, reflecting a perturbed AIS morphological plastic response to hyperexcitability arising from proteasome inhibition, a phenotype rescued by ectopic Ecm29 expression or NKCC1 inhibition. Together, our findings support the idea that neuronal maturation requires regulation of proteasomal distribution controlled by Ecm29.

A Pilot Study of a Tactile Measurement System Using Lateral Skin Stretch on Foot Plantar Surface

The purpose of this study is to develop smart equipment to quantify plantar tactile sensibility for early diagnosis and tracking of peripheral neuropathy caused by diabetes mellitus. In this paper, we present new testing equipment composed of a plantar tactile stimulation platform with a moving contactor to stretch the skin tangentially, a response switch for each tactile stimulus, a motor control box, and a personal computer for psychophysical data processing. This testing equipment offers more precise measurements and is easy to use compared to conventional testing tools such as von Frey monofilaments, pin-prick testing devices, and current perception threshold testers. Using our testing equipment, we showed that the plantar tactile threshold for the tangential stretching stimulus on the first metatarsal head of the feet ranges from approximately 10 to 60 μm for subjects without diabetic foot problems. Meanwhile, the plantar tactile threshold of some subjects suspected of having diminished protective sensation by the Semmens-Weinstein monofilament testing is approximately 100 μm or more. These preliminary results suggest that our testing equipment based on the plantar sensation elicited by lateral stretching of skin has the potential for quantitative diagnosis in subjects suspected of suffering from neuropathy, and for monitoring changes over time to sustain quality of life.