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==Publications== {{medline-entry |title=[[CCN3]] Signaling Is Differently Regulated in Placental Diseases Preeclampsia and Abnormally Invasive Placenta. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33304321 |abstract=An adequate development of the placenta includes trophoblast differentiation with the processes of trophoblast migration, invasion, cellular senescence and apoptosis which are all crucial to establishing a successful pregnancy. Altered placental development and function lead to placental diseases such as preeclampsia (PE) which is mainly characterized by insufficient trophoblast invasion and abnormally invasive placenta ([[AIP]]) disorders ([i]Placenta accreta[/i], [i]increta[/i], or [i]percreta)[/i] which are characterized by excessive trophoblast invasion. Both of them will cause maternal and fetal morbidity/mortality. However, the etiology of these diseases is still unclear. Our previous study has shown that the matricellular protein [i]nephroblastoma overexpressed[/i] (NOV, [[CCN3]]) induces G0/G1 cell cycle arrest, drives trophoblast cells into senescence and activates FAK and Akt kinases resulting in reduced cell proliferation and enhanced migration capability of the human trophoblast cell line SGHPL-5. The present study focuses on whether [[CCN3]] can alter cell cycle-regulated pathways associated with trophoblast senescence and invasion activity in pathological versus gestational age-matched control placentas. Cell cycle regulator proteins were investigated by immunoblotting and qPCR. For localization of [[CCN3]], p16, p21, and Cyclin D1 proteins, co-immunohistochemistry was performed. In early-onset PE placentas, [[CCN3]] was expressed at a significantly lower level compared to gestational age-matched controls. The decrease of [[CCN3]] level is associated with an increase in p53, Cyclin E1 and pRb protein expression, whereas the level of cleaved Notch-1, p21, Cyclin D1, pFAK, pAKT, and pmTOR protein decreased. In term [[AIP]] placentas, the expression of [[CCN3]] was significantly increased compared to matched term controls. This increase was correlated to an increase in p53, p16, p21, Cyclin D1, cleaved Notch-1, pFAK, pAkt, and pmTOR whereas pRb was significantly decreased. However, in late PE and early [[AIP]] placentas, no significant differences in [[CCN3]], p16, p21, Cyclin D1, p53, and cleaved Notch-1 expression were found when matched to appropriate controls. [[CCN3]] expression levels are correlated to markers of cell cycle arrest oppositely in PE and [[AIP]] by activating the FAK/AKT pathway in [[AIP]] or down-regulating in PE. This may be one mechanism to explain the different pathological features of placental diseases, PE and [[AIP]]. |keywords=* CCN3 * abnormally invasive placenta * invasion * preeclampsia * senescence * trophoblast |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701218 }} {{medline-entry |title=[Aryl hydrocarbon receptor interacting protein ([[AIP]]) in human dermis during aging.] |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33280328 |abstract=The aim of this work was to examine the content of aryl hydrocarbon receptor interacting protein ([[AIP]]) in fibroblasts of human dermis from 20 weeks of pregnancy until 85 years old, and defining of a role of [[AIP]] in age-dependent changes in the number of fibroblasts in the dermis. [[AIP]], proliferating cells nuclear antigen ([[PCNA]]) were detected with indirect immunohistochemical technique. Results showed that a portion of fibroblasts with positive staining for [[AIP]] in the dermis is gradually increased from 20 weeks of pregnancy until 85 years old. A total number and percent of [[PCNA]] positive fibroblasts in dermis decreased with progression of age. Most sufficient age-dependent reduction in a total and [[PCNA]] positive number of dermal fibroblast was observed from antenatal until 40 years of life. Correlation analysis showed that both age-dependent decrease in the number of fibroblasts and retardation of their proliferation are significantly associated with age-related increase in the number of [[AIP]] positive fibroblasts in dermis. Results allow to suggest that [[AIP]] is involved in age-dependent decrease in the number and proliferation of fibroblasts in human dermis. |keywords=* AIP * PCNA * aging * fibroblasts * skin }} {{medline-entry |title=Sex-Specific Association between Serum Vitamin D Status and Lipid Profiles: A Cross-Sectional Study of a Middle-Aged and Elderly Chinese Population. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32350171 |abstract=Studies have shown that vitamin D status might be associated with dyslipidaemia, but results are conflicting and there might exist sex differences. The aim of our study was to explore the sex-specific association between vitamin D status and serum lipids and atherogenic index of plasma ([[AIP]], a predictor for atherosclerosis) among Chinese middle-aged and elderly adults. A total of 4,021 middle-aged and elderly participants from a health management centre were included in this cross-sectional study. The individuals were classified into tertiles according to serum 25(OH)D. Linear and logistic regression models were used to estimate the association between vitamin D levels and serum lipids among the tertiles. The mean serum 25(OH)D level was 21.60 (16.60-27.20) ng/mL in all participants. After adjusting for potential confounders, a 10 ng/mL increase in 25(OH)D was associated with decreases of 1.156 mmol/L in triglycerides (TGs) and 0.068 in the [[AIP]] and an increase of 0.051 mmol/L in high-density lipoprotein cholesterol (HDL-C) in all subjects. In addition, 25(OH)D deficiency was associated with an increased prevalence of hypertriglyceridaemia (odds ratio (OR), 1.880; 95% confidence interval (CI), 1.351-2.615), hypoalphalipoproteinaemia/HDL (OR, 1.505; 95% CI, 1.146-1.977) and abnormal [[AIP]] (OR, 1.933; 95% CI, 1.474-2.534) in males, and 25(OH)D-deficient women had a 2.02-fold higher risk for hypoalphalipoproteinaemia/HDL than women with sufficient 25(OH)D levels (95% CI, 1.044-3.904; all p values <0.05). Vitamin D deficiency was positively associated with the prevalence of dyslipidaemia and abnormal [[AIP]] in the middle-aged and elderly Chinese population. And this association was stronger in men than in women. |keywords=* atherogenic index of plasma * dyslipidaemia * gerontology * sex difference * vitamin D |full-text-url=https://sci-hub.do/10.3177/jnsv.66.105 }} {{medline-entry |title=The oblique effect: The relationship between profiles of visuospatial preference, cognition, and brain connectomics in older adults. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31654648 |abstract=The oblique effect (OE) describes the visuospatial advantage for identifying stimuli oriented horizontally or vertically rather than diagonally; little is known about brain aging and the OE. We investigated this relationship using the Judgment of Line Orientation (JLO) in 107 older adults (∼age = 67.8 ± 6.6; 51% female) together with neuropsychological tests of executive functioning (EF), attention/information processing ([[AIP]]), and neuroimaging. Only JLO lines falling between 36-54° or 126-144° were considered oblique. To quantify the oblique effect, we calculated z-scores for oblique errors (zOblique = #oblique errors/#oblique lines), and similarly, horizontal vertical line errors (zHV), and a composite measure of oblique relative to HV errors (zOE). Composite z-scores of EF and [[AIP]] reflected domains associated with JLO performance. Graph theory analysis integrated T1-derived volumetry and diffusion MRI-derived white matter tractography into connectivity matrices analyzed for select network properties. Participants produced more zOblique than zHV errors (p < 0.001). Age was not associated with zOE adjusting for sex, education, and MMSE. Similarly adjusted linear regression models revealed that lower EF was associated with a larger oblique effect (p < 0.001). Modular analyses of neural connectivity revealed a differential patterns of network affiliation that varied by high versus low group status determined via median split of zOblique and zHV errors, separately. Older adults exhibit the oblique effect and it is associated with specific cognitive processes and regional brain networks that may facilitate future investigations of visuospatial preference in aging. |mesh-terms=* Aged * Brain * Cognition * Connectome * Diffusion Tensor Imaging * Executive Function * Female * Humans * Judgment * Male * Middle Aged * Neuropsychological Tests * Pattern Recognition, Visual * Spatial Processing |keywords=* Aging * Executive function * Oblique effect * Perception * Structural connectivity * Visuospatial processing |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887099 }} {{medline-entry |title=A logic of choice: Problematizing the documentary reality of Canadian aging in place policies. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30832929 |abstract=The home environment is pivotal in the lives of older people, intimately intertwined with one's sense of self and belonging. Aging in place ([[AIP]]), continuing to live in the same or familiar place or community for as long as possible not only fulfills a neoliberal and economic imperative but aligns with the wishes of a majority of older Canadians, who prefer to age in place. Despite policies' contributions to differing experiences of aging, the potential bearing of the narratives embedded within [[AIP]] or age-friendly policies remains unexamined. Within an institutional ethnography method of inquiry, this study applied Bacchi's "What's the Problem Represented to be?" (WPR) approach to structure the discovery of governing narratives about familial care work embedded within seven Canadian aging in place policies at the municipal, provincial, and federal level. I analyzed these policies for their role in coordinating the experiences of caring for an older adult who is aging in place in London, Canada's first age-friendly city. Of particular interest for this study is uncovering whether these texts recognize the work, and in particular the information work, of providing care to an older adult who is [[AIP]]. The policies' overall focus on self-reliance, independence, and resourcefulness frames aging in place as a process that can and should be responsibly managed. Information is introduced as a helpful tool to secure and preserve older adults' independence and usefulness to their community. The policies' problematizations frame successful aging in place as governed through a logic of choice, where a complex problem is framed as a matter of choice. Ultimately, however, while the policies offer a number of different "choices" for older adults to [[AIP]], a critical unpacking of the problematizations reveals the choice to [[AIP]] to be illusory. There is only one option presented in the policies and that is to [[AIP]]. |mesh-terms=* Aged * Canada * Choice Behavior * Female * Health Services for the Aged * Humans * Independent Living * Male * Policy * Self Concept |keywords=* Age-friendly communities * Aging in place * Canada * Family caregivers * Governmentality * Housing * Information work * Institutional ethnography * Policy * Problematizations |full-text-url=https://sci-hub.do/10.1016/j.jaging.2019.01.002 }} {{medline-entry |title=Enhanced basal late sodium current appears to underlie the age-related prolongation of action potential duration in guinea pig ventricular myocytes. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29357519 |abstract=Aging hearts have prolonged QT interval and are vulnerable to oxidative stress. Because the QT interval indirectly reflects the action potential duration (APD), we examined the hypotheses that 1) the APD of ventricular myocytes increases with age; 2) the age-related prolongation of APD is due to an enhancement of basal late Na current (I ); 3) inhibition of I may protect aging hearts from arrhythmogenic effects of hydrogen peroxide (H O ). Experiments were performed on ventricular myocytes isolated from one-month (young) and one-year (old) guinea pigs (GPs). The APD of myocytes from old GPs was significantly longer than that from young GPs and was shortened by the I inhibitors GS967 and tetrodotoxin. The magnitude of I was significantly larger in myocytes from old than from young GPs. The CaMKII inhibitors KN-93 and [[AIP]] and the Na 1.5-channel blocker MTSEA blocked the I . There were no significant differences between myocytes from young and old GPs in L-type Ca current and the rapidly- and slowly-activating delayed rectifier K currents, although the inward rectifier K current was slightly decreased in myocytes from old GPs. H O induced more early afterdepolarizations in myocytes from old than from young GPs. The effect of H O was attenuated by GS967. The results suggest that 1) the APD of myocytes from old GPs is prolonged, 2) a CaMKII-mediated increase in Na 1.5-channel I is responsible for the prolongation of APD, and 3) Inhibition of I may be beneficial for maintaining electrical stability under oxidative stress in myocytes of old GPs. |keywords=* Aging * Oxidative stress * Ventricular myocytes * action potential duration * late sodium current |full-text-url=https://sci-hub.do/10.1152/japplphysiol.00916.2017 }} {{medline-entry |title=Building IoT Services for Aging in Place Using Standard-Based IoT Platforms and Heterogeneous IoT Products. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29019964 |abstract=An aging population and human longevity is a global trend. Many developed countries are struggling with the yearly increasing healthcare cost that dominantly affects their economy. At the same time, people living with old adults suffering from a progressive brain disorder such as Alzheimer's disease are enduring even more stress and depression than those patients while caring for them. Accordingly, seniors' ability to live independently and comfortably in their current home for as long as possible has been crucial to reduce the societal cost for caregiving and thus give family members peace of mind, called 'aging in place' ([[AIP]]). In this paper we present a way of building [[AIP]] services using standard-based IoT platforms and heterogeneous IoT products. An [[AIP]] service platform is designed and created by combining previous standard-based IoT platforms in a collaborative way. A service composition tool is also created that allows people to create [[AIP]] services in an efficient way. To show practical usability of our proposed system, we choose a service scenario for medication compliance and implement a prototype service which could give old adults medication reminder appropriately at the right time (i.e., when it is time to need to take pills) through light and speaker at home but also wrist band and smartphone even outside the home. |keywords=* Internet of Things (IoT) * Web of Objects * aging in place * composite virtual object * medication compliance * oneM2M * service composition * standard-based IoT platforms * virtual object |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677444 }} {{medline-entry |title=Atherogenic Indices Are Increased in Elderly Patients with Unipolar Depression-Case-Control Analysis. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28402173 |abstract=Blood lipids are widely used in monitoring the risk of cardiovascular diseases; however, atherogenic indices are more precise markers. The aim of the study was to determine differences in atherogenic indices in elderly patients with unipolar depression (DEP) compared with nondepressed elderly patients (nonDEP) using case-control analysis. Fasting serum lipid profiles were measured in 564 (depressed: n = 282, nondepressed: n = 282, 83.7% (n = 236) women in both groups) Caucasian inpatients aged ≥60, with mean age 76.9 years. Patients from both groups were matched for age and sex. Atherogenic index of plasma ([[AIP]]) was calculated as log (triglycerides/HDL cholesterol). Castelli atherogenic indices were calculated as follows: AI is the ratio of low-density lipoprotein (LDL) cholesterol to high-density lipoprotein (HDL) cholesterol and AI is the ratio of total cholesterol to HDL cholesterol. HDL levels were significantly decreased in depressed patients (48.2 ± 14.4 mg/dL vs. 54.5 ± 17.7 mg/dL). No other differences in lipid profile were found. We found that all three analyzed atherogenic indices were increased in depressed patients ([[AIP]]: 0.41 ± 0.28 vs. 0.33 ± 0.27, AI : 2.90 ± 1.41 vs. 2.42 ± 1.07, AI : 4.51 ± 1.84 vs. 3.79 ± 1.21). We found associations between depression severity and reduced level of HDL (β = -0.02) or increased [[AIP]] (β = 1.66). All three atherogenic indices were increased in elderly patients with depression. Since depression and age are associated with elevated risk of cardiovascular events, elderly patients with depression should be carefully monitored for abnormal lipid status to reduce their cardiovascular risk. The role of lipid abnormalities in the pathogenesis of depression requires further studies. |mesh-terms=* Aged * Aged, 80 and over * Aging * Atherosclerosis * Biomarkers * Case-Control Studies * Cholesterol, LDL * Depressive Disorder * Female * Health Status Indicators * Humans * Lipoproteins, HDL * Male * Risk Factors * Triglycerides |keywords=* atherogenic indices * cholesterol * depression * lipids * old age psychiatry * triglycerides |full-text-url=https://sci-hub.do/10.1089/met.2017.0008 }} {{medline-entry |title=Feline hypersomatotropism and acromegaly tumorigenesis: a potential role for the [[AIP]] gene. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28119176 |abstract=Acromegaly in humans is usually sporadic, however up to 20% of familial isolated pituitary adenomas are caused by germline sequence variants of the aryl-hydrocarbon-receptor interacting protein ([[AIP]]) gene. Feline acromegaly has similarities to human acromegalic families with [[AIP]] mutations. The aim of this study was to sequence the feline [[AIP]] gene, identify sequence variants and compare the [[AIP]] gene sequence between feline acromegalic and control cats, and in acromegalic siblings. The feline [[AIP]] gene was amplified through PCR using whole blood genomic DNA from 10 acromegalic and 10 control cats, and 3 sibling pairs affected by acromegaly. PCR products were sequenced and compared with the published predicted feline [[AIP]] gene. A single nonsynonymous SNP was identified in exon 1 ([[AIP]]:c.9T > G) of two acromegalic cats and none of the control cats, as well as both members of one sibling pair. The region of this SNP is considered essential for the interaction of the [[AIP]] protein with its receptor. This sequence variant has not previously been reported in humans. Two additional synonymous sequence variants were identified ([[AIP]]:c.481C > T and [[AIP]]:c.826C > T). This is the first molecular study to investigate a potential genetic cause of feline acromegaly and identified a nonsynonymous [[AIP]] single nucleotide polymorphism in 20% of the acromegalic cat population evaluated, as well as in one of the sibling pairs evaluated. |mesh-terms=* Acromegaly * Aging * Amino Acid Sequence * Animals * Carcinogenesis * Case-Control Studies * Cat Diseases * Cats * Female * Genetic Predisposition to Disease * Intracellular Signaling Peptides and Proteins * Male * Polymorphism, Single Nucleotide |keywords=* AIP * Acromegaly * Feline * Genetic * Hypersomatotropism * SNP |full-text-url=https://sci-hub.do/10.1016/j.domaniend.2016.11.005 }} {{medline-entry |title=Digital Clock Drawing: differentiating "thinking" versus "doing" in younger and older adults with depression. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25222513 |abstract=Psychomotor slowing has been documented in depression. The digital Clock Drawing Test (dCDT) provides: (i) a novel technique to assess both cognitive and motor aspects of psychomotor speed within the same task and (ii) the potential to uncover subtleties of behavior not previously detected with non-digitized modes of data collection. Using digitized pen technology in 106 participants grouped by Age (younger/older) and Affect (euthymic/unmedicated depressed), we recorded cognitive and motor output by capturing how the clock is drawn rather than focusing on the final product. We divided time to completion (TTC) for Command and Copy conditions of the dCDT into metrics of percent of drawing (%Ink) versus non-drawing (%Think) time. We also obtained composite Z-scores of cognition, including attention/information processing ([[AIP]]), to explore associations of %Ink and %Think times to cognitive and motor performance. Despite equivalent TTC, %Ink and %Think Command times (Copy n.s.) were significant (AgeXAffect interaction: p=.03)-younger depressed spent a smaller proportion of time drawing relative to thinking compared to the older depressed group. Command %Think time negatively correlated with [[AIP]] in the older depressed group (r=-.46; p=.02). Copy %Think time negatively correlated with [[AIP]] in the younger depressed (r=-.47; p=.03) and older euthymic groups (r=-.51; p=.01). The dCDT differentiated aspects of psychomotor slowing in depression regardless of age, while dCDT/cognitive associates for younger adults with depression mimicked patterns of older euthymics. |mesh-terms=* Adult * Aged * Aging * Analysis of Variance * Cognition Disorders * Depression * Female * Humans * Male * Middle Aged * Neuropsychological Tests * Psychomotor Disorders * Risk Factors * Statistics as Topic * Stroke * Thinking * Time Factors |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310546 }} {{medline-entry |title=The continued success of registered nurse care coordination in a state evaluation of aging in place in senior housing. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24731918 |abstract=Older adults prefer to age in place, remaining in their home as their health care needs intensify. In a state evaluation of aging in place ([[AIP]]), the University of Missouri Sinclair School of Nursing and Americare System Inc, Sikeston, MO, developed an elder housing facility to be an ideal housing environment for older adults to test the [[AIP]] care delivery model. An evaluation of the first 4 years (2005-2008) of the [[AIP]] program at TigerPlace (n = 66) revealed that the program was effective in restoring health and maintaining independence while being cost-effective. Similar results evaluating the subsequent 4 years (2009-2012) of the program (N = 128) revealed positive health outcomes (fall risk, gait velocity, Functional Ambulation Profile, handgrips, Short-Form 12 Physical Health, Short-Form 12 Mental Health, and Geriatric Depression Scale); slightly negative activities of daily living, independent activities of daily living, and Mini-Mental State Examination; and positive cost-effectiveness results. Combined care and housing costs for any resident who was receiving additional care services and qualified for nursing home care (n = 44) was about $20,000 less per year per person than nursing home care. Importantly, residents continued to live in private apartments and were encouraged to be as independent as possible through the end of life. |mesh-terms=* Aged * Aged, 80 and over * Female * Geriatric Nursing * Homes for the Aged * Humans * Independent Living * Long-Term Care * Male * Missouri * Nurse's Role * Nurses * Nursing Homes * Program Evaluation |keywords=* Aging in place * Assisted living * Elderly * Nurse care coordination * Nursing home |full-text-url=https://sci-hub.do/10.1016/j.outlook.2014.02.005 }} {{medline-entry |title=Associations between vascular risk and mood in euthymic older adults: preliminary findings. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23759292 |abstract=Vascular risk has been associated with late-life depression, but it is less certain whether it is also associated with the endorsement of depressive symptoms among euthymic older adults. We explore whether vascular risk is associated with endorsement of depressive symptoms among euthymic older adults and examine associations with cognitive function. Fifty-seven adults (50-89 years), were assessed for: 1) vascular risk (Framingham Stroke Risk Profile, FSRP); 2) depressive mood (Center for Epidemiologic Studies Depression, CESD self-rating questionnaire; Hamilton Depression Rating Scale, HDRS clinical interview); and 3) cognitive domains, (Learning and Memory, L-M; Attention and Information Processing, [[AIP]]; Executive Function, EF; Semantic Language, SL). Significant correlations were observed between FSRP and both depression scales, independent of age. No significant correlations were observed between HDRS and any cognitive domain; in contrast, CESD correlated significantly with L-M, [[AIP]] and EF but not SL. FSRP correlated significantly with L-M and EF measures only. Regression analyses revealed that 11.5% of the variance in HDRS scores was explained by FSRP, whereas CESD scores were explained by EF (20.8% of variance). Vascular risk was associated with endorsement of depressive symptoms in euthymic older adults. However, the patterns of associations with the two depression scales are distinct and may reflect both differences in administration and item characteristics. A limitation of this study was the exclusion of individuals with subclinical depression, leading to a restricted range on depression scales; future studies should include a full population sample to more fully explore low mood in late-life. |mesh-terms=* Affect * Age Factors * Aged * Aged, 80 and over * Cognition * Depression * Female * Humans * Male * Middle Aged * Neuropsychological Tests * Psychiatric Status Rating Scales * Regression Analysis * Risk Factors * Stroke |keywords=* Aging * cardiovascular risk * depression |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564289 }} {{medline-entry |title=Aging in place versus nursing home care: comparison of costs to Medicare and Medicaid. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21846081 |abstract=The objective of this study was to compare the community-based, long-term care program called Aging in Place ([[AIP]]) and nursing home care, in terms of cost to the Medicare and Medicaid programs. A retrospective cohort design was used in this study of 39 nursing home residents in the Midwest who were matched with 39 [[AIP]] participants. The [[AIP]] program consisted of a combination of Medicare home health, Medicaid home and community-based services (HCBS), and intensive nurse care coordination. Controlling for high inpatient Medicare cost in the 6 months prior and the 10 most frequently occurring chronic conditions, multiple regression was used to estimate the relationship of the [[AIP]] program on Medicare and Medicaid costs. Total Medicare and Medicaid costs were $1,591.61 lower per month in the [[AIP]] group (p < 0.01) when compared with the nursing home group over a 12-month period. The findings suggest that the provision of nurse-coordinated HCBS and Medicare home health services has potential to provide savings in the total cost of health care to the Medicaid program while not increasing the cost of the Medicare program. |mesh-terms=* Aging * Health Care Costs * Humans * Medicaid * Medicare * Missouri * Nursing Homes * Residence Characteristics * United States |full-text-url=https://sci-hub.do/10.3928/19404921-20110802-01 }} {{medline-entry |title=Proteasomal adaptation to environmental stress links resistance to proteotoxicity with longevity in Caenorhabditis elegans. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18467495 |abstract=The burden of protein misfolding is believed to contribute to aging. However, the links between adaptations to conditions associated with protein misfolding and resistance to the time-dependent attrition of cellular function remain poorly understood. We report that worms lacking aip-1, a homologue of mammalian AIRAP (arsenic-inducible proteasomal 19S regulatory particle-associated protein), are not only impaired in their ability to resist exposure to arsenite but also exhibit shortened lifespan and hypersensitivity to misfolding-prone proteins under normal laboratory conditions. Mammals have a second, constitutively expressed AIRAP-like gene (AIRAPL) that also encodes a proteasome-interacting protein, which shares with AIRAP the property of enhancing peptide accessibility to the proteasome's active site. Genetic rescue experiments suggest that features common to the constitutively expressed worm [[AIP]]-1 and mammalian AIRAPL (but missing in the smaller, arsenite-inducible AIRAP) are important to lifespan extension. In worms, a single AIRAP-related protein links proteasomal adaptation to environmental stress with resistance to both proteotoxic insults and maintenance of animal life span under normal conditions. |mesh-terms=* Adaptation, Physiological * Animals * Arsenites * Caenorhabditis elegans * Caenorhabditis elegans Proteins * Cell Line * Endoplasmic Reticulum * Environment * Humans * Intracellular Membranes * Longevity * Mice * Phenotype * Proteasome Endopeptidase Complex * Protein Binding * Protein Folding * RNA-Binding Proteins * Sequence Homology, Amino Acid |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2383958 }} {{medline-entry |title=Influence of age and gender on the clinical expression of acute intermittent porphyria based on molecular study of porphobilinogen deaminase gene among Swiss patients. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11591889 |abstract=Acute intermittent porphyria ([[AIP]]) is an inherited disorder in the heme biosynthetic pathway caused by a partial deficiency of porphobilinogen (PBG) deaminase. Clinically, [[AIP]] is characterized as acute neurovisceral attacks that are often precipitated by exogenous factors such as drugs, hormones, and alcohol. An early detection of mutation carriers is essential for prevention of acute attacks by avoiding precipitating factors. This study was aimed at analyzing genetic defects causing [[AIP]] among Swiss families to further investigate aspects concerning the clinical expression of the disease. The PBGD gene of index patients from 21 Swiss [[AIP]] families was systematically analyzed by denaturing gradient gel electrophoresis of polymerase chain reaction (PCR) amplified DNA fragments and direct sequencing. Five new mutations insA503, del L170, T190I, P241S, and R321H, as well as three known mutations (R26H, R173Q and W283X) were detected. Twelve of the 21 index patients (57%) carried the prevalent mutation W283X previously found among the Swiss [[AIP]] population. Family-specific mutations were then screened among relatives of the index patients. Among the 107 studied individuals, 58 carried a PBGD gene mutation--30 were overt [[AIP]] patients and 28 were asymptomatic carriers. The apparent rate of overt disease in the study cohort was 52%, which is significantly higher than the previously reported penetrance of 10-20%. To further examine the clinical expression of [[AIP]], the cumulative life-time risk was calculated among 58 mutation-positive individuals after stratifying for age. The result shows a linear increase of the percentage of the symptomatic patients with age, reaching up to 75% among carriers aged over 60. Moreover, statistical analysis of the gender distribution among patients and asymptomatic carriers indicated that the disease was more frequently expressed among females than males (Fisher's exact test two sided, p= (0.001). This comprehensive search for genetic defects in the PBGD gene confirmed the existence of a prevalent mutation W283X among Swiss [[AIP]] patients, as well as a number of family-private mutations. Genetic analysis laid a groundwork for further studies such as the effects of gender and age on the clinical expression of [[AIP]]. |mesh-terms=* Adolescent * Adult * Aged * Aged, 80 and over * Aging * Child * Child, Preschool * DNA Mutational Analysis * Female * Heterozygote * Humans * Hydroxymethylbilane Synthase * Infant * Infant, Newborn * Male * Middle Aged * Molecular Diagnostic Techniques * Pedigree * Porphyria, Acute Intermittent * Risk Assessment * Sex Characteristics * Switzerland |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1950064 }} {{medline-entry |title=Developmental change in activity of red cell porphobilinogen deaminase and its electrophoretic variant in the Japanese population. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/8165902 |abstract=The activity of porphobilinogen deaminase (PBGD), an enzyme whose partial deficiency is associated with acute intermittent porphyria ([[AIP]]), changes during development. Little is known about the postnatal change of PBGD activity and the prevalence of its electrophoretic variant in the Japanese population. The activity of PBGD was measured fluorometrically in 194 infants aged 0-12 months, while isoelectric focusing of PBGD was performed in 400 healthy Japanese adults aged 20-45 years and 30 children with various hematological disorders aged 1-15 years. The PBGD level was 1.9 times higher in the neonates than in the adults, decreased abruptly during the first month of life, and reached the adult level at the age of 9 months. None of the 400 healthy Japanese adults and the 30 children with hematological disorders showed any electrophoretic variant. These results suggest that there is no need to consider any polymorphism in the gene dose study of PBGD and that the biochemical screening of [[AIP]] is applicable to since the late infancy. |mesh-terms=* Adult * Aging * Asian Continental Ancestry Group * Child * Child, Preschool * Electrophoresis * Erythrocytes * Female * Humans * Hydroxymethylbilane Synthase * Infant * Infant, Newborn * Japan * Male * Middle Aged |full-text-url=https://sci-hub.do/10.1111/j.1442-200x.1994.tb03122.x }} {{medline-entry |title=[Bone mineral density of lumbar spine and its relations to biological and lifestyle factors in middle-aged and aged Japanese women (Part 2). Effects of age and menopause on bone mineral density evaluated by biochemical markers of bone metabolism]. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/7807708 |abstract=Bone mineral density of the lumbar spine (BMD) and biochemical markers for bone turnover were examined to study the mechanisms of age-related and menopause-related bone loss. We measured BMD of the lumbar spine and serum bone alkaline phosphatase (B-[[AIP]]) and bone gla-protein (BGP) as markers of bone formation and fasting urinary creatinine-adjusted hydroxyproline (Hyp/Cr) and calcium (Ca/Cr) as those of bone resorption in 166 community-dwelling Japanese women. A highly significant positive correlation between age and each of the biochemical markers, except for Ca/Cr, was observed. This relationship was not linear. Marked elevation in the levels of the markers was found in women in their sixth decade women compared with those in their fifth. All the markers correlated inversely with the BMD and these relationships remained significant after elimination of the effect of age by partialization. When analyzing the subjects in each five-year age group, the positive correlation of Hyp/Cr with Ca/Cr was significant in the subjects aged 45 to 49 and the negative correlation of Hyp/Cr with BMD was significant in those aged 50 to 54. B-[[AIP]] correlated positively with BGP in the subjects aged between 50 and 54 and inversely with BMD in those aged between 55 and 59. These correlations were significant. Thus, intercorrelations between the markers were observed five years earlier than were correlations between the markers and BMD. Such associations appeared earlier in terms of the markers for bone resorption than in terms of the markers for bone formation.(ABSTRACT TRUNCATED AT 250 WORDS) |mesh-terms=* Adult * Aged * Aged, 80 and over * Aging * Asian Continental Ancestry Group * Biomarkers * Bone Density * Bone and Bones * Female * Humans * Japan * Life Style * Lumbar Vertebrae * Middle Aged * Postmenopause |full-text-url=https://sci-hub.do/10.1265/jjh.49.807 }}
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