Suppression of cell cycle progression by Jun dimerization protein (JDP2) involves down-regulation of cyclin A2

We report here a novel role for Jun dimerization protein-2 (JDP2) as a regulator of the progression of normal cells through the cell cycle. To determine the role of JDP2 in vivo, we generated Jdp2 knock-out (Jdp2KO) mice by targeting exon 1 to disrupt the site of initiation of transcription. The healing of wounded skin of Jdp2KO mice proceeded more rapidly than that of control mice and more proliferating cells were found at wound margins. Fibroblasts derived from embryos of Jdp2KO mice proliferated more rapidly and formed more colonies than wild-type fibroblasts. JDP2 was recruited to the promoter of the gene for cyclin A2 (ccna2) at a previously unidentified AP-1 site. Cells lacking Jdp2 had elevated levels of cyclin A2 mRNA. Moreover, reintroduction of JDP2 resulted in repression of transcription of ccna2 and of cell cycle progression. Thus, transcription of the gene for cyclin A2 appears to be a direct target of JDP2 in the suppression of cell proliferation

Impact of the day of the week on the discontinuation of broad-spectrum antibiotic prescriptions; a multi-centered observational study

To encourage and guide antimicrobial stewardship team (AST) activity and promote appropriate antibiotic use, we studied the impact of day of the week on the initiation and discontinuation of antibiotic administration. This was a multicenter observational study conducted at 8 Japanese hospitals from April 1 to September 30, 2019, targeting patients who underwent treatment with broad-spectrum antibiotics, such as anti-methicillin-resistant Staphylococcus aureus agents and anti-pseudomonal agents. We compared the weekly numbers of initiations and discontinuations of antibiotic prescription on each day of the week or on the days after a holiday. There was no statistical difference in the number of antibiotic initiations on both weekdays and the day after a holiday. However, antibiotic discontinuation was significantly higher from Tuesday onward than Monday and from the second day than the first day after a holiday. Similar trends were observed regardless of the categories of antibiotics, hospital and admission ward, and AST activity. This study suggests that broad-spectrum antibiotics tend to be continued during weekends and holidays and are most likely to be discontinued on Tuesday or the second day after a holiday. This was probably due to behavioral factors beyond medical indications, requiring further antimicrobial stewardship efforts in the future

Jun Dimerization Protein 2 Controls Senescence and Differentiation via Regulating Histone Modification

Transcription factor, Jun dimerization protein 2 (JDP2), binds directly to histones and DNAs and then inhibits the p300-mediated acetylation both of core histones and of reconstituted nucleosomes that contain JDP2 recognition DNA sequences. JDP2 plays a key role as a repressor of adipocyte differentiation by regulation of the expression of the gene C/EBPδ via inhibition of histone acetylation. Moreover, JDP2-deficient mouse embryonic fibroblasts (JDP2−/− MEFs) are resistant to replicative senescence. JDP2 inhibits the recruitment of polycomb repressive complexes (PRC1 and PRC2) to the promoter of the gene encoding p16Ink4a, resulting from the inhibition of methylation of lysine 27 of histone H3 (H3K27). Therefore, it seems that chromatin-remodeling factors, including the PRC complex controlled by JDP2, may be important players in the senescence program. The novel mechanisms that underline the action of JDP2 in inducing cellular senescence and suppressing adipocyte differentiation are reviewed

The Role of the OR Region in BSE Pathogenesis

Conformational conversion of the cellular isoform of prion protein PrPC, into the abnormally folded, amyloidogenic isoform, PrPSc, is a key pathogenic event in prion diseases including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals. We previously reported that the octapeptide repeat (OR) region could be dispensable for converting PrPC into PrPSc after infection with RML prions. We demonstrated that mice transgenically expressing mouse PrP with deletion of the OR region on the PrP-knockout background, designated Tg(PrPΔOR)/Prnp0/0 mice, did not reduced susceptibility to RML scrapie prions, with abundant accumulation of PrPScΔOR in their brains. We show here that Tg(PrPΔOR)/Prnp0/0 mice were highly resistant to BSE prions, developing the disease with markedly elongated incubation times after infection with BSE prions. The conversion of PrPΔOR into PrPScΔOR was markedly delayed in their brains. These results suggest that the OR region may have a crucial role in the conversion of PrPC into PrPSc after infection with BSE prions. However, Tg(PrPΔOR)/Prnp0/0 mice remained susceptible to RML and 22L scrapie prions, developing the disease without elongated incubation times after infection with RML and 22L prions. PrPScΔOR accumulated only slightly less in the brains of RML- or 22L-infected Tg(PrPΔOR)/Prnp0/0 mice than PrPSc in control wild-type mice. Taken together, these results indicate that the OR region of PrPC could play a differential role in the pathogenesis of BSE prions and RML or 22L scrapie prions. IMPORTANCE Structure-function relationship studies of PrPC conformational conversion into PrPSc are worthwhile to understand the mechanism of the conversion of PrPC into PrPSc. We show here that, by inoculating the three different prion strains of RML, 22L and BSE prions, into Tg(PrP∆OR)/Prnp0/0 mice, the OR region could play a differential role in the conversion of PrPC into PrPSc after infection with RML or 22L scrapie prions and BSE prions. PrPΔOR was efficiently converted into PrPScΔOR after infection with RML and 22L prions. However, the conversion of PrPΔOR into PrPScΔOR was markedly delayed after infection with BSE prions. Further investigation into the role of the OR region in the conversion of PrPC into PrPSc after infection with BSE prions might be helpful for understanding the pathogenesis of BSE prions

HbA1c and telemedicine during COVID-19

Aims/Introduction: To investigate whether the COVID-19 pandemic affected behavioral changes and glycemic control in patients with diabetes and to conduct a survey of telemedicine during the pandemic. Materials and Methods: In this retrospective study, a total of 2,348 patients were included from 15 medical facilities. Patients were surveyed about their lifestyle changes and attitudes toward telemedicine. Hemoglobin A1c (HbA1c) levels were compared among before (from June 1 to August 31, 2019) and in the first (from June 1 to August 31, 2020) and in the second (from June 1 to August 31, 2021) year of the pandemic. A survey of physician attitudes toward telemedicine was also conducted. Results: The HbA1c levels were comparable between 2019 (7.27 ± 0.97%), 2020 (7.28 ± 0.92%), and 2021 (7.25 ± 0.94%) without statistical difference between each of those 3 years. Prescriptions for diabetes medications increased during the period. The frequency of eating out was drastically reduced (51.7% in 2019; 30.1% in 2020), and physical activity decreased during the pandemic (48.1% in 2019; 41.4% in 2020; 43.3% in 2021). Both patients and physicians cited increased convenience and reduced risk of infection as their expectations for telemedicine, while the lack of physician–patient interaction and the impossibility of consultation and examination were cited as sources of concern. Conclusions: Our data suggest that glycemic control did not deteriorate during the COVID-19 pandemic with appropriate intensification of diabetes treatment in patients with diabetes who continued to attend specialized diabetes care facilities, and that patients and physicians shared the same expectations and concerns about telemedicine