Characterization of Common Minke Whale (Balaenoptera Acutorostrata) Cell Lines Immortalized with the Expression of Cell Cycle Regulators.

Primary cultured cells cannot proliferate infinite. The overcoming of this limit can be classified as immortalization. Bypass of p16 senescence protein induces efficient immortalization various types of mammalians is previously reported. However, the Cetacea species is not known. Here, that common minke whale-derived cells can be immortalized with a combination of human genes, mutant cyclin-dependent kinase 4 (CDK4R24C ), cyclin D1, and Telomerase Reverse Transcriptase (TERT) is reported. These results indicate that the function of cell cycle regulators in premature senescence is evolutionarily conserved. This study describes the conserved roles of cell cycle regulators in the immortalization of cells from humans to Cetacea species. Furthermore, using RNA-seq based on next-generation sequencing, the gene expression profiles of immortalized cells are compared with parental cells as well as those immortalized with SV40 large T antigen, which is once a popular method for cellular immortalization. The profiling results show that newly established common minke-whale-derived immortaliozed cells have completely different profiles from SV40 cells. This result indicates that the expression of mutant CDK4, cyclin D1, and TERT enables to establish immortalized cell lines with different biological nature from SV40 expressing cells.

Association between behavioural and psychological symptoms of dementia and residence status in patients with Alzheimer's disease.

BACKGROUND: Examining the relationship between the behavioural and psychological symptoms of dementia (BPSD) and residence status is crucial to improving BPSD and reducing the burden on caregivers. However, studies on how BPSD differ between individuals living at home and those in institutional settings are lacking. We conducted a questionnaire survey among healthcare providers (HCPs) involved in dementia care and nursing to clarify the characteristics of BPSD by residence status in patients with Alzheimer's disease (AD) living at home or in facilities. METHODS: We sent questionnaires to HCPs and asked them to answer questions on up to five cases that needed treatment for BPSD and who received long-term care insurance services from 1 April 2016 to 31 March 2017. Responses were received for 371 cases, of which 130 diagnosed with AD were analyzed. The patients were divided into two groups: patients with AD living at home (home care group) and patients with AD living in facilities (facility care group). A Chi-square test was used to identify differences between the two groups. A binomial logistic regression analysis was also conducted to clarify the association between residence status and BPSD. RESULTS: Of the 130 patients, 72 lived at home (home care group) and 58 resided in facilities (facility care group). None of the background factors was significantly different between the two groups. The Chi-square test indicated that sleep disturbance was significantly more common in the facility care group (60.3% in the facility care group vs. 33.3% in the home care group, P = 0.003), while the logistic regression analysis indicated that sleep disturbance was significantly associated with residence status (odds ratio: 2.529, P = 0.038). CONCLUSIONS: Sleep disturbances were more frequently observed among patients with AD living in institutions than among those living in their homes.

Effects of a multicomponent day-care program on cerebral blood flow in patients with mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) is a prodromal phase of dementia and is considered an important period for intervention to prevent conversion to dementia. It has been well established that multicomponent day-care programs including exercise training, cognitive intervention and music therapy have beneficial effects on cognition, but the effects on cerebral blood flow (CBF) in MCI remain unknown. This study examined whether a multicomponent day-care program would have beneficial effects on the longitudinal changes of CBF in MCI patients. METHODS: Participants were 24 patients with MCI attending a day-care program; they underwent two 99 mTc-ethyl cysteinate dimer single photon emission computed tomography scans during the study period. We evaluated the association between the changes of regional cerebral blood flow and the attendance rate. RESULTS: There was a significant negative correlation between the reduction of regional CBF in the right parietal region and the attendance rate. We found no significant relation between the baseline CBF images and the attendance rate. CONCLUSIONS: Our results suggest that continuous participation in a multicomponent day-care program might prevent reduction in brain activity in patients with MCI.

The Multicomponent Day-Care Program Prevents Volume Reduction in a Memory-Related Brain Area in Patients with Mild Cognitive Impairment.

INTRODUCTION: Mild cognitive impairment (MCI) is considered an important period for interventions to prevent progression to dementia. Nonpharmacological interventions for MCI include exercise training, cognitive intervention, and music therapy. These play an important role in improving cognitive function, but their effects on brain plasticity in individuals with MCI are largely unknown. We investigated the effects of a multicomponent day-care program provided by the University of Tsukuba Hospital on the longitudinal brain volume changes in MCI patients. METHODS: MCI patients who participated in the multicomponent day-care program and underwent whole-brain magnetic resonance imaging (MRI) twice during their participation (n = 14), were included. We divided them into two groups according to their attendance rate and conducted a between-group analysis of longitudinal volume changes in the whole cerebral cortex. Regional brain volumes derived from the patients' MRI were calculated with Freesurfer 6.0.0. RESULTS: The neuroimaging analysis demonstrated that the left rostral anterior cingulate cortex volume was significantly preserved in the high-attendance group compared to that of the low-attendance group. CONCLUSION: Our results suggest that continuous participation in a multicomponent day-care program could help prevent a volume reduction in memory-related brain areas in patients with MCI.

Immortalization of cells derived from domestic dogs through expressing mutant cyclin-dependent kinase 4, cyclin D1, and telomerase reverse transcriptase.

Dog is the first animal that was established as a close partner of human beings. Based on the vast genetic diversity and breeding, dogs exhibit unique genetic evolution and diversity from Chihuahua to St. Bernard. The safety tests of the pharmacological products also included domestic dogs as the test subjects. Although the safety confirmation test of chemicals for human use is important, the welfare of experimental animals requires special consideration. In this study, we cultured domestic dog-derived primary fibroblasts isolated from their muscle tissues. Furthermore, we successfully immortalized them through lentivirus-mediated gene transfer of mutant cyclin-dependent kinase 4 (CDK4), cyclin D1, and telomere reverse transcriptase (TERT). We further demonstrated that the established immortalized domestic dog-derived fibroblasts retained the characteristics of the original parental cells. These cells might act a suitable in vivo model system to replace the implication of animals for evaluating the potential toxicity of pharmacological chemicals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-021-00504-0.