Literature review of trends in research on COVID-19 in older adults in Japan: A text mining analysis

This study aimed to determine the current state of research on COVID-19 in older adults in Japan. We searched original articles published in Japanese journals from January 15, 2020, to August 4, 2021, with the terms “older adult” and “COVID-19”，and identified 33 articles. We analyzed them by quantitative text mining with KH Coder （ver.3.0） software, and keyword in context concordance was used to confirm the context and content of group-generated words, and each group was given a name that characterized its contents. The most frequent words were “COVID-19,” “infection,” and “activity.” In the co-occurrence network analysis of words, “PCR test,” “fever,” and “COVID-19” had high mediation centrality. We used subgraph detection to classify the top 50 words into 5 groups: “Diagnosis by PCR test, and respiratory and circulatory management for severe cases,” “Presented to the clinic with fever as the major symptom,” “Effective treatment method,” “Reduction of social participation by refraining from going out,” and “Adopting a new lifestyle.” In future, the data on more cases and long-term follow-up are needed. There is an urgent need to support vulnerable older adults at risk of social isolation to help them develop and maintain a new lifestyle in a society

RIMB-1/RIM-binding protein and UNC-10/RIM redundantly regulate presynaptic localization of the voltage-gated calcium channel in Caenorhabditis elegans.

Presynaptic active zones (AZ) contain many molecules essential for neurotransmitter release and are assembled in a highly organized manner. A network of adaptor proteins known as Cytomatrix at the AZ (CAZ), is important for shaping the structural characteristics of AZ. RIM-binding protein (RBP) family are binding partners of the CAZ protein RIM and also bind the voltage-gated calcium channels (VGCC) in mice and flies. Here, we investigated the physiological roles of RIMB-1, the homolog of RBPs in the nematode RIMB-1 is expressed broadly in neurons and predominantly localized at presynaptic sites. Loss-of-function animals of displayed slight defects in motility and response to pharmacological inhibition of synaptic transmission, suggesting a modest involvement of in synapse function. We analyzed genetic interactions of by testing candidate genes and by an unbiased forward genetic screen for enhancer. Both analyses identified the RIM homolog UNC-10 that acts together with RIMB-1 to regulate presynaptic localization of the P/Q-type VGCC UNC-2/Ca2. We also find that the precise localization of RIMB-1 to presynaptic sites requires presynaptic UNC-2/Ca2. RIMB-1 has multiple FN3 and SH3 domains. Our transgenic rescue analysis with RIMB-1 deletion constructs revealed a functional requirement of a C-terminal SH3 in regulating UNC-2/Ca2 localization. Together, these findings suggest a redundant role of RIMB-1/RBP and UNC-10/RIM to regulate the abundance of UNC-2/Ca2 at the presynaptic AZ in , depending on the bidirectional interplay between CAZ adapter and channel proteins.Presynaptic active zones (AZ) are highly organized structures for synaptic transmission with characteristic networks of adapter proteins called Cytomatrix at the AZ (CAZ). In this study, we characterized a CAZ protein RIMB-1, named for RIM-binding protein (RBP), in the nematode Through systematic analyses of genetic interactions and an unbiased genetic enhancer screen of , we revealed a redundant role of two CAZ proteins RIMB-1/RBP and UNC-10/RIM in regulating presynaptic localization of UNC-2/Ca2, a voltage-gated calcium channel (VGCC) critical for proper neurotransmitter release. Additionally, the precise localization of RIMB-1/RBP requires presynaptic UNC-2/Ca2. These findings provide new mechanistic insight about how the interplay among multiple CAZ adapter proteins and VGCC contributes to the organization of presynaptic AZ

RIMB-1/RIM-Binding Protein and UNC-10/RIM Redundantly Regulate Presynaptic Localization of the Voltage-Gated Calcium Channel in Caenorhabditis elegans

Presynaptic active zones (AZs) contain many molecules essential for neurotransmitter release and are assembled in a highly organized manner. A network of adaptor proteins known as cytomatrix at the AZ (CAZ) is important for shaping the structural characteristics of AZ. Rab3-interacting molecule (RIM)-binding protein (RBP) family are binding partners of the CAZ protein RIM and also bind the voltage-gated calcium channels (VGCCs) in mice and flies. Here, we investigated the physiological roles of RIMB-1, the homolog of RBPs in the nematode Caenorhabditis elegans RIMB-1 is expressed broadly in neurons and predominantly localized at presynaptic sites. Loss-of-function animals of rimb-1 displayed slight defects in motility and response to pharmacological inhibition of synaptic transmission, suggesting a modest involvement of rimb-1 in synapse function. We analyzed genetic interactions of rimb-1 by testing candidate genes and by an unbiased forward genetic screen for rimb-1 enhancer. Both analyses identified the RIM homolog UNC-10 that acts together with RIMB-1 to regulate presynaptic localization of the P/Q-type VGCC UNC-2/Cav2. We also find that the precise localization of RIMB-1 to presynaptic sites requires presynaptic UNC-2/Cav2. RIMB-1 has multiple FN3 and SH3 domains. Our transgenic rescue analysis with RIMB-1 deletion constructs revealed a functional requirement of a C-terminal SH3 in regulating UNC-2/Cav2 localization. Together, these findings suggest a redundant role of RIMB-1/RBP and UNC-10/RIM to regulate the abundance of UNC-2/Cav2 at the presynaptic AZ in C. elegans, depending on the bidirectional interplay between CAZ adaptor and channel proteins.SIGNIFICANCE STATEMENT Presynaptic active zones (AZs) are highly organized structures for synaptic transmission with characteristic networks of adaptor proteins called cytomatrix at the AZ (CAZ). In this study, we characterized a CAZ protein RIMB-1, named for RIM-binding protein (RBP), in the nematode Caenorhabditis elegans Through systematic analyses of genetic interactions and an unbiased genetic enhancer screen of rimb-1, we revealed a redundant role of two CAZ proteins RIMB-1/RBP and UNC-10/RIM in regulating presynaptic localization of UNC-2/Cav2, a voltage-gated calcium channel (VGCC) critical for proper neurotransmitter release. Additionally, the precise localization of RIMB-1/RBP requires presynaptic UNC-2/Cav2. These findings provide new mechanistic insight about how the interplay among multiple CAZ adaptor proteins and VGCC contributes to the organization of presynaptic AZ