Two-dimensional distribution of Gi2α in the plasma membrane: a critical evaluation by immunocytochemistry

AbstractCaveolae have been postulated as a center for signal transduction, because many signaling molecules are concentrated in caveolin-rich fractions. We took Gi2α as an example and examined whether it is constitutively concentrated in caveolae. First, the behavior of caveolin and Gi2α in density-equilibrium ultracentrifugation was reexamined. By collecting fractions efficiently, caveolin and Gi2α were found to distribute differently. Secondly, by novel immunocytochemical methods it was found that the labeling density of Gi2α was 2.29 times higher in caveolae than in the non-caveolar plasma membrane. The results indicate that the concentration of Gi2α in caveolae is lower than deduced from most biochemical studies

Perspective Chapter: Prevention of COVID-19 at Our University

With the rapid spread of the new coronavirus, COVID-19, many universities switched to online classes to promote social distancing and reduce the risk of infection. The Ministry of Education, Culture, Sports, Science and Technology, however, requested universities hold face-to-face classes whenever possible. Therefore, after the national emergency was lifted, our university, the Kinjo University in Hakusan, launched the “Kinjo Infection Control Team” to help prevent infection on campus. Our university was one of the first universities in the Hokuriku region to resume face-to-face classes. Infection control teams were originally organized at hospitals and other medical facilities by professionals specializing in infection prevention and control. Although our university did not have an affiliated hospital, we had medical professionals, including doctors and nurses, as well as virology researchers, who conducted environmental patrols, hand hygiene education and monitoring, and infection education for students and faculty. The most important countermeasures against the spread of infectious disease in universities are the maintenance of the campus environment and the behavioral changes of students. To maintain a safe learning environment during a pandemic, it is necessary to consider the best measures to prevent infection from various aspects so that we can avoid spreading infectious diseases, and also maintain maximum student activity and provide a safe learning environment at all times

Safety and Efficacy of FIT039 for Verruca Vulgaris: A Placebo-Controlled, Phase I/II Randomized Controlled Trial

TRIAL DESIGN: Human papillomavirus infection causes verruca vulgaris. CDK9 inhibitor FIT039 inhibits DNA virus proliferation in animal models. We conducted a multicenter, single-blind, placebo-controlled, randomized phase I/II clinical trial evaluating the safety and efficacy of FIT039 against verruca vulgaris. METHODS: Target lesions were treated with liquid nitrogen once, and a FIT039 patch or placebo patch was applied for 14 days. The primary endpoint was lesion disappearance. The secondary endpoints were safety and changes in dimension, cross-sectional area, and the number of petechial lesions. RESULTS: A total of 24 participants were randomly allocated to the FIT039 (n = 13, median age, 54 years) and placebo (n = 11, median age, 62 years) groups. Verruca vulgaris did not disappear. FIT039 decreased the dimension to 76% of the initial value on day 29, followed by an increase to 98% on day 57. Placebo showed a monotonic increase to 107% on day 57. Changes in the cross-sectional area and petechiae number were comparable between the groups. CONCLUSIONS: No drug-related adverse reactions occurred. FIT039 efficacy was not determined in this study

Calaxin is required for cilia-driven determination of vertebrate laterality

Sasaki, K., Shiba, K., Nakamura, A. et al. Calaxin is required for cilia-driven determination of vertebrate laterality. Commun Biol 2, 226 (2019). https://doi.org/10.1038/s42003-019-0462-

Targeted deletion of the C-terminus of the mouse adenomatous polyposis coli tumor suppressor results in neurologic phenotypes related to schizophrenia

Background: Loss of adenomatous polyposis coli (APC) gene function results in constitutive activation of the canonical Wnt pathway and represents the main initiating and rate-limiting event in colorectal tumorigenesis. APC is likely to participate in a wide spectrum of biological functions via its different functional domains and is abundantly expressed in the brain as well as in peripheral tissues. However, the neuronal function of APC is poorly understood. To investigate the functional role of Apc in the central nervous system, we analyzed the neurological phenotypes of Apc 1638T/1638T mice, which carry a targeted deletion of the 3′ terminal third of Apc that does not affect Wnt signaling. Results: A series of behavioral tests revealed a working memory deficit, increased locomotor activity, reduced anxiety-related behavior, and mildly decreased social interaction in Apc 1638T/1638T mice. Apc 1638T/1638T mice showed abnormal morphology of the dendritic spines and impaired long-term potentiation of synaptic transmission in the hippocampal CA1 region. Moreover, Apc 1638T/1638T mice showed abnormal dopamine and serotonin distribution in the brain. Some of these behavioral and neuronal phenotypes are related to symptoms and endophenotypes of schizophrenia. Conclusions: Our results demonstrate that the C-terminus of the Apc tumor suppressor plays a critical role in cognitive and neuropsychiatric functioning. This finding suggests a potential functional link between the C-terminus of APC and pathologies of the central nervous system

Microtubule stabilizer reveals requirement of Ca2+-dependent conformational changes of microtubules for rapid coiling of haptonema in haptophyte algae

A haptonema is an elongated microtubule-based motile organelle uniquely present in haptophytes. The most notable and rapid movement of a haptonema is ‘coiling’, which occurs within a few milliseconds following mechanical stimulation in an unknown motor-independent mechanism. Here, we analyzed the coiling process in detail by high-speed filming and showed that haptonema coiling was initiated by left-handed twisting of the haptonema, followed by writhing to form a helix from the distal tip. On recovery from a mechanical stimulus, the helix slowly uncoiled from the proximal region. Electron microscopy showed that the seven microtubules in a haptonema were arranged mostly in parallel but that one of the microtubules often wound around the others in the extended state. A microtubule stabilizer, paclitaxel, inhibited coiling and induced right-handed twisting of the haptonema in the absence of Ca2+, suggesting changes in the mechanical properties of microtubules. Addition of Ca2+ resulted in the conversion of haptonematal twist into the planar bends near the proximal region. These results indicate that switching microtubule conformation, possibly with the aid of Ca2+-binding microtubule-associated proteins is responsible for rapid haptonematal coiling