Structural basis for Y2 receptor-mediated neuropeptide Y and peptide YY signaling.

Neuropeptide Y (NPY) and its receptors are expressed in various human tissues including the brain where they regulate appetite and emotion. Upon NPY stimulation, the neuropeptide Y1 and Y2 receptors (Y1R and Y2R, respectively) activate GI signaling, but their physiological responses to food intake are different. In addition, deletion of the two N-terminal amino acids of peptide YY (PYY(3-36)), the endogenous form found in circulation, can stimulate Y2R but not Y1R, suggesting that Y1R and Y2R may have distinct ligand-binding modes. Here, we report the cryo-electron microscopy structures of the PYY(3-36)‒Y2R‒Gi and NPY‒Y2R‒Gi complexes. Using cell-based assays, molecular dynamics simulations, and structural analysis, we revealed the molecular basis of the exclusive binding of PYY(3-36) to Y2R. Furthermore, we demonstrated that Y2R favors G protein signaling over ß-arrestin signaling upon activation, whereas Y1R does not show a preference between these two pathways.

Accelerated aging phenotypes in the retinal pigment epithelium of Zmpste24-deficient mice.

Age-related macular degeneration (AMD) is a chronic and progressive disease characterized by degeneration of the retinal pigment epithelium (RPE) and retina that ultimately leads to loss of vision. The pathological mechanisms of AMD are not fully known. Cellular senescence, which is a state of cell cycle arrest induced by DNA-damage or aging, is hypothesized to critically affect the pathogenesis of AMD. In this study, we examined the relationship between cellular senescence and RPE/retinal degeneration in mouse models of natural aging and accelerated aging. We performed a bulk RNA sequencing of the RPE cells from adult (8 months old) and naturally-aged old (24 months old) mice and found that common signatures of senescence and AMD pathology - inflammation, apoptosis, and blood vessel formation - are upregulated in the RPE of old mice. Next, we investigated markers of senescence and the degree of RPE/retinal degeneration in Zmpste24-deficient (Zmpste24-/-) mice, which is a model for progeria and accelerated aging. We found that Zmpste24-/- mice display markedly greater level of senescence-related markers in RPE and significant RPE/retinal degeneration compared to wild-type mice, in a manner consistent with natural aging. Overall, these results provide support for the association between cellular senescence of RPE and the pathogenesis of AMD, and suggest the use of Zmpste24-/- mice as a novel senescent RPE model of AMD.

Comparison of short-term condylar positional changes in mandibular prognathism after surgery-first approach: Symmetric setback versus asymmetric setback.

The aim of this study was to compare how the displacement of the mandibular condyle changed after symmetric or asymmetric mandibular setback surgery using the surgery-first approach (SFA). Patients who underwent mandibular setback surgery using the SFA were selected and divided into a symmetry group (n = 18) with differences of less than 2 mm between the right and left setback, and an asymmetry group (n = 18) with a difference of greater than 2 mm. Cone-beam computed tomography (CBCT)-generated cephalograms were obtained after three-dimensional superimposition of CBCT images taken before surgery (T0), within one week after surgery (T1), and seven months after surgery (T2). The condylar positions were measured. Condylar positional changes according to time were compared between the two groups and correlation analysis was performed. There were significant positional changes in mandibular condyles over time in both groups. However, most of these changes returned to their initial state. In the asymmetry group, there was a greater internal rotation of the mandibular condyle on the lesser setback side. The correlation analysis results revealed that only the setback difference was associated with rotational displacement of the condyle on the lesser setback side at two time points (T1-T0, T2-T0). In the SFA, significant condylar displacement occurred immediately after both symmetric and asymmetric mandibular setback surgery, and the right/left difference in mandibular setback showed a significant positive correlation with rotational displacement. Although more significant rotational displacement of the mandibular condyle was observed after asymmetric mandibular setback surgery, the amount was not large enough to be clinically significant.

Structural basis of neuropeptide Y signaling through Y1 receptor.

Neuropeptide Y (NPY) is highly abundant in the brain and involved in various physiological processes related to food intake and anxiety, as well as human diseases such as obesity and cancer. However, the molecular details of the interactions between NPY and its receptors are poorly understood. Here, we report a cryo-electron microscopy structure of the NPY-bound neuropeptide Y1 receptor (Y1R) in complex with Gi1 protein. The NPY C-terminal segment forming the extended conformation binds deep into the Y1R transmembrane core, where the amidated C-terminal residue Y36 of NPY is located at the base of the ligand-binding pocket. Furthermore, the helical region and two N-terminal residues of NPY interact with Y1R extracellular loops, contributing to the high affinity of NPY for Y1R. The structural analysis of NPY-bound Y1R and mutagenesis studies provide molecular insights into the activation mechanism of Y1R upon NPY binding.

Dual conformational recognition by Z-DNA binding protein is important for the B-Z transition process.

Left-handed Z-DNA is radically different from the most common right-handed B-DNA and can be stabilized by interactions with the Zα domain, which is found in a group of proteins, such as human ADAR1 and viral E3L proteins. It is well-known that most Zα domains bind to Z-DNA in a conformation-specific manner and induce rapid B-Z transition in physiological conditions. Although many structural and biochemical studies have identified the detailed interactions between the Zα domain and Z-DNA, little is known about the molecular basis of the B-Z transition process. In this study, we successfully converted the B-Z transition-defective Zα domain, vvZαE3L, into a B-Z converter by improving B-DNA binding ability, suggesting that B-DNA binding is involved in the B-Z transition. In addition, we engineered the canonical B-DNA binding protein GH5 into a Zα-like protein having both Z-DNA binding and B-Z transition activities by introducing Z-DNA interacting residues. Crystal structures of these mutants of vvZαE3L and GH5 complexed with Z-DNA confirmed the significance of conserved Z-DNA binding interactions. Altogether, our results provide molecular insight into how Zα domains obtain unusual conformational specificity and induce the B-Z transition.

Relationship between sleep and obesity among U.S. and South Korean college students.

BACKGROUND: Little is known about the relationship between sleep and obesity in young adults, particularly college students. This study examined the relationship between sleep (i.e., sleep duration and quality) and obesity in a large and diverse binational sample of college students. METHODS: Analyses were based on a 40-item paper survey from 2016/2017 to 2017/2018 academic years, with a 72% response rate. The samples were 1578 college students aged 18-25 years from five universities (two in the U.S. and three in South Korea). Weight and height were measured objectively; other measures (e.g., health behaviors) were self-reported. Multinomial logistic regression was used to assess the association between sleep duration and independent variables (race/nationality, gender, and BMI). Poisson regression was used to examine the relationship between sleep quality and independent variables. RESULTS: Overall, blacks had a higher adjusted odds ratio (AOR) of short sleep (< 7 h/night) than whites (AOR = 1.74, P < .01); overweight participants had a higher AOR of short sleep than normal weight participants (AOR = 1.52, P < .01); and obese participants had a higher AORs of both short and long sleep (> 9 h/night) (AOR = 1.67, P < .01; AOR = 1.79, P < .05, respectively). Among men, being black, overweight, and obesity were associated with short sleep (P < .05), whereas only obesity was related to short sleep among women (P < .05). In analyses stratified by race and nationality, overweight and obesity were related to short sleep among blacks only (P < .05). Overall, sleep quality (getting enough sleep to feel rested in the morning in the past 7 days) was worse in blacks and South Koreans than whites (P < .05), worse in women than men (P < .05), and worse in participants with obesity than normal weight participants (P < .05). CONCLUSIONS: Obesity was associated with both short (< 7 h/night) and long sleep duration (> 9 h/night) and poor sleep quality among all participants. In comparison with whites, blacks were more like to have short sleep, and blacks and South Koreans had worse sleep quality. Further investigations using a larger sample of college students in multiple countries may be helpful to identify target populations who are at a greater risk of obesity and sleep problems.

Experience of sport stacking in Korean older adults.

Today sedentary lifestyles are a major public health concern and there are many evidences related to physical inactivity. The well-documented evidence is that regular physical activity is an essential part for improving overall health with advancing aging and the most efficient means playing roles of rehabilitation and prehabilitation. However, there are few activity programs which could motivate older adults to continue and maintain their active lifestyles. The purpose of the current study was to describe experience of sport stacking which applied to Korean older adults in the first time. Eighteen older adults living in the community in Seoul which was the capital and largest metropolis of the Republic of Korea participated in the study. A qualitative interview and a survey were conducted and data were analyzed by interpretive content analysis. Individual, semistructured, face-to-face interviews were recorded, transcribed, condensed and coded to find themes. The main themes were identified regarding older adults' experience of sport stacking: enjoyment of sport stacking, attitudes toward sport stacking as a physical activity program, and benefits from sport stacking. In conclusions, Korean older adults had positive experience of sport stacking and it was necessary for developing strategies to spread it as the physical activity program for older persons in Korea to improve their health and quality of life.

Development of strategies for changing in physical activity behaviors on older adults with disabilities.

The purpose of this study was to develop strategies for promoting physical activity for the disabled older adults who were in the transtheoretical model of precontemplation, contemplation, and preparation stages about participating physical activities for promoting healthy life-styles. In order to achieve this goal, we developed a preliminary strategy for promoting physical activity for the elderly with disabilities based on the data gathered through the ground-work studies and the results of the research on the changes of the exercise behavior directly investigated from the elderly with disabilities. Then the strategies were verified to completion of the final promoting strategies. The elderly with disabilities in the three stages of precontemplation, contemplation, and preparation should develop strategies to think positively about themselves and their surroundings as well as strengthen their appropriate healthy behaviors. Additionally, families, physicians, and healthy seniors who spent time with disabled older adults could help to promote physical activities. However, overall administrative support, in-stitutional system construction, and public policy support were needed and it suggested that multifaceted supports and a variety of cooperation were necessary to improve a quality of life among older adults with disabilities.

Restrictions of physical activity participation in older adults with disability: employing keyword network analysis.

Older adults with disability might have been increasing due to the rapid aging of society. Many studies showed that physical activity is an essential part for improving quality of life in later lives. Regular physical activity is an efficient means that has roles of primary prevention and secondary prevention. However, there were few studies regarding older adults with disability and physical activity participation. The purpose of this current study was to investigate restriction factors to regularly participate older adults with disability in physical activity by employing keyword network analysis. Two hundred twenty-nine older adults with disability who were over 65 including aging with disability and disability with aging in type of physical disability and brain lesions defined by disabled person welfare law partook in the open questionnaire assessing barriers to participate in physical activity. The results showed that the keyword the most often used was 'Traffic' which was total of 21 times (3.47%) and the same proportion as in the 'personal' and 'economical'. Exercise was considered the most central keyword for participating in physical activity and keywords such as facility, physical activity, disabled, program, transportation, gym, discomfort, opportunity, and leisure activity were associated with exercise. In conclusion, it is necessary to educate older persons with disability about a true meaning of physical activity and providing more physical activity opportunities and decreasing inconvenience should be systematically structured in Korea.

Feasibility of integrating the "Healthy moves for aging well" program into home care aide services for frail older adults.

The purpose of the study was to assess the feasibility of implementing simple, safe, non-equipment evidence-based movements (Healthy Moves for Aging Well program) using an affordable and sustainable homecare-aide based delivery model that reaches the maximum possible number of frail older adults living at home in Illinois. Two local agencies were asked to identify two experienced home care aides and two inexperienced home care aides (n= 8). Each home care aides delivered the Healthy Moves to four clients (n= 16). Eight home care aides visited the client in the home and were asked to deliver the Healthy Moves program on a regular basis for a four-month time period. Outcome measures included a pre-and post- survey, a functional fitness test (older adults), and interviews. Evaluation procedures focused on older adult participants, homecare aids, and sites. The results showed that both interview and survey data revealed that most participants including older adults, home care aides, and site directors had a positive perception and high satisfaction with the program. Specially, 100% of older adult participants reported that they would recommend the program to others. Additionally, seniors and home care aides reported that they enjoyed working with each other on the program and both site directors reported that dissemination of the program in the State of Illinois employing home care aides was feasible and acceptable. Our study results indicate that Healthy Moves for Aging Well could be safely and successfully be disseminated to frail older adults in the State of Illinois.

Factors influencing physical activity in older adults.

The purpose of this study was to investigate the extent to which Korean seniors report employing different motivational and social cognitive strategies related to physical activity, and to evaluate which motivational and social cognitive strategies were related to physical activity, and which motivational and social cognitive strategies differentiate between high active and low-active Korean seniors. Community-dwelling older adults (N = 187) participated in the study and completed questionnaires assessing self-reported physical activity and a range of motivational and social cognitive variables. The results showed that physical activity was predicted by quality goal-setting practices, self-efficacy, social support from family and physical activity self-regulation subscales of social support and exercise planning and scheduling. Between the groups of highly physically active and low-active participants, we observed differences in satisfaction with life, self-efficacy, quality goal-setting practices, and self-regulatory strategies related to self-monitoring, goal-setting, social support and time management. In conclusion, these findings indicate that physical activity promotion efforts among Korean older adults should focus on enhancing self-efficacy, social support, and self-regulation skills.

The impact of a national strategy to increase physical activity among older adults on national organizations.

This study was designed to evaluate the impact of the National Blueprint (NB) on the policies, programs, and organizational culture of selected national organizations. The theoretical model selected to assess the impact of the NB on organizational behavior was Burke's system theory of organizational change. Three organizations, AARP, the American College of Sports Medicine (ACSM), and the Administration on Aging (AoA), were selected for the study. Two individuals in each of these organizations were selected for interview. Semistructured interviews and document reviews were used in the data-collection process. Findings showed that the publication and establishment of the NB resulted in changes in the operating procedures of AARP, ACSM, and AoA. The results were broadly consistent with Burke's system theory of organizational change. The publication of the NB was shown to affect the behavior of organizational leaders, organizational culture, policies, programs, and individual and organizational performance. The new information generated has increased our understanding of the impact of health campaigns on organizational behavior.