REN
Renin precursor (EC 3.4.23.15) (Angiotensinogenase)
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Three-dimensional chromatin architecture and gene-gene interactions impact gene expression. We assembled this information, in silico, for the human renin gene (REN). We searched for chromatin contacts and boundaries and the locations of super-enhancers that are involved in cell specific differentiation. The REN promoter was connected via RNA polymerase II binding to promoters of 12 neighboring genes on chromosome 1q32.1 over a distance of 762,497 bp. This constitutes a regulatory archipelago. The genes formed 3 topologically associated domains (TADs), as follows: TAD1: ZC3H11A, SNRPE, LINC00303; SOX13; TAD2: ETNK2, REN, KISS1, GOLT1A; TAD3: PLEKHA6, LINC00628, PPP1R15B, PIK3C2B, MDM4. REN in TAD2, was isolated from its neighboring genes in TAD1 and TAD3 by CTCF-binding sites that serve as insulators. TAD1 and TAD3 genes SOX13 and LINC00628 overlapped super-enhancers, known to reside near nodes regulating cell identity, and were co-expressed in various tissues, suggesting co-regulation. REN was also connected with 62 distant genes genome-wide, including the angiotensin II type 1 receptor gene. The findings lead us to invoke the following novel hypothesis. While the REN promoter is isolated from neighboring super-enhancers in most cells by insulators, these insulators break down with cell age to permit the inappropriate expression of REN in non-kidney cells by using the neighboring super-enhancers, resulting in expression in a wider spectrum of tissues, contributing to aging-related immune system dysregulation, cardiovascular diseases and cancers. Research is needed to confirm this hypothesis experimentally.
MeSH Terms
- Aging
- Computer Simulation
- Epistasis, Genetic
- Humans
- Promoter Regions, Genetic
- Renin
Keywords
- Aging
- Diseases of aging
- Gene expression
- Gene–gene interaction
- Genomics
- Longevity
- Renin-angiotensin system
- Topologically associated domains
Hispanics, and particularly foreign-born Mexican Americans, have been shown to fare better across a range of health outcomes than might be expected given the generally higher levels of socioeconomic disadvantage in this population, a phenomena termed the "Hispanic Paradox". Previous research on social disparities in cognitive aging, however, has been unable to address both race/ethnicity and nativity (REN) in a nationally-representative sample of US adults leaving unanswered questions about potentially "paradoxical" advantages of Mexican ethnic-origins and the role of nativity, socioeconomic status (SES), and enclave residence. We employ biennial assessments of cognitive functioning to study prevalent and incident cognitive impairment (CI) within the three largest US REN groups: US-born non-Hispanic whites (US-NHW), US-born non-Hispanic blacks (US-NHB), US-born Mexican Americans (US-MA), and foreign-born Mexican Americans (FB-MA). Data come from a nationally-representative sample of community-dwelling older adults in the Health and Retirement Study linked with the 2000 Census and followed over 10 years (N = 8,433). Large disadvantages in prevalent and incident CI were observed for all REN minorities respective to US-born non-Hispanic whites. Individual and neighborhood SES accounted substantially for these disadvantages and revealed an immigrant advantage: FB-MA odds of prevalent CI were about half those of US-NHW and hazards of incident CI were about half those of US-MA. Residence in an immigrant enclave was protective of prevalent CI among FB-MA. The findings illuminate important directions for research into the sources of cognitive risk and resilience and provide guidance about CI screening within the increasingly diverse aging US population.
MeSH Terms
- Cognitive Dysfunction
- Continental Population Groups
- Emigrants and Immigrants
- Female
- Health Surveys
- Hispanic Americans
- Humans
- Longitudinal Studies
- Male
- Mexican Americans
- Middle Aged
- Residence Characteristics
- Social Class
- United States
Keywords
- cognitive aging
- immigrant enclaves
- race/ethnicity and nativity
- socioeconomic factors
The objective of the current study was to compare the clinical features and outcomes between younger and older patients with skull base chordoma (SBC). In this retrospective study, patients with SBC who underwent surgical treatment between February 2005 and December 2014 were included. Clinical features were recorded, including the signal intensity ratio of tumor to brain stem in T1 (RT1), T2 (RT2), and enhanced T1 (REN) sequences in primary patients with complete preoperative magnetic resonance images. The clinical features and outcomes were compared between younger (≤24 years) and older patients (≥25 years). In the present study, 238 patients were included. Younger patients experience more aggressive resection than do older patients (P = 0.045), and the SBCs of younger patients tended to be located in the occipitocervical region compared with older patients (P = 0.007). REN value in the younger group was lower than in the older group (P = 0.014), and the value of RT2 was higher in younger patients than in older patients (P = 0.015). The risk of progression was higher in older patients compared with younger patients (P = 0.030); the risk of having a poor neurologic status in older patients was higher than in younger patients (P = 0.044). In younger patients, there were more SBCs located in the occipitocervical regions, and younger patients tended to undergo more aggressive resection. The tumor signal intensity of younger patients with SBC was higher in T2 images but lower in enhanced T1 images. A younger age was a favorable factor for a longer progression-free survival and a good neurologic status at follow-up.
MeSH Terms
- Adolescent
- Adult
- Age Factors
- Aged
- Aging
- Child
- Child, Preschool
- Chordoma
- Disease-Free Survival
- Female
- Humans
- Image Processing, Computer-Assisted
- Karnofsky Performance Status
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Retrospective Studies
- Skull Base Neoplasms
- Treatment Outcome
- Young Adult
Keywords
- Age
- Clinical feature
- Outcome
- Skull base chordoma
Flupirtine is a nonopioid, central analgesic without antipyretic or antiphlogistic properties. Flupirtine-MR is an oral modified-release formulation with a 100 mg fast-input and a 300 mg portion with slow protracted release. Single- (D01) and repeated-dose (D03-D09) pharmacokinetics of 400 mg flupirtine-MR were investigated in patients with severe renal dysfunction (REN: N: 12; 21 50 years of age; creatinine clearance (CLCr)≤30 mL/min per 1.73 m2 body surface area (BSA)) and healthy older subjects (EN1: N: 8; 60-69 years; CLCr≥80 mL/min and EN2: N: 8; ≥70 years, CLCr≥60 mL/min) vs. young healthy control subjects (YN: N: 12; 21-40 years; CLCr≥90 mL/min). Renal dysfunction led to a relatively small average increase in systemic exposure to flupirtine: on D09, the REN : YN-ratios were 1.37 (95% confidence interval (CI): 1.03-1.82), 1.21 (CI: 1.01-1.45), and 1.34 (CI: 1.09-1.64) for Css,0, Css,max, and Css,av, respectively. A similar increase in exposure was observed in older subjects: the respective EN1:YN-ratios were 1.30 (CI: 0.95-1.79), 1.23 (CI: 1.01-1.49), and 1.23 (CI: 0.98-1.54); the EN2:YN-ratios were 1.50 (CI: 1.10-2.04), 1.16 (CI: 0.85-1.41), and 1.41 (CI: 1.12-1.79), respectively. Neither age nor renal function was a predominant factor of pharmacokinetic variability. Single and repeated doses of flupirtine-MR were very well tolerated. The average renal and age effects were small, but the use of a lower starting dose (1/2 tablet) is recommended since some of these subjects might have relatively high exposure levels.
MeSH Terms
- Administration, Oral
- Adult
- Age Factors
- Aged
- Aging
- Aminopyridines
- Analgesics
- Area Under Curve
- Biomarkers
- Creatinine
- Delayed-Action Preparations
- Drug Administration Schedule
- Drug Monitoring
- Female
- Glomerular Filtration Rate
- Humans
- Kidney
- Kidney Diseases
- Male
- Metabolic Clearance Rate
- Middle Aged
- Prospective Studies
- Severity of Illness Index
- Young Adult
Nutrient resorption from senescing photosynthetic organs is a powerful mechanism for conserving nitrogen (N) and phosphorus (P) in infertile environments. Evolution has resulted in enhanced differentiation of conducting tissues to facilitate transport of photosynthate to other plant parts, ultimately leading to phloem. Such tissues may also serve to translocate N and P to other plant parts upon their senescence. Therefore, we hypothesize that nutrient resorption efficiency (RE, % of nutrient pool exported) should correspond with the degree of specialization of these conducting tissues across the autotrophic branches of the Tree of Life. To test this hypothesis, we had to compare members of different plant clades and lichens within a climatic region, to minimize confounding effects of climatic drivers on nutrient resorption. Thus, we compared RE among wide-ranging basal clades from the principally N-limited subarctic region, employing a novel method to correct for mass loss during senescence. Even with the limited numbers of species available for certain clades in this region, we found some consistent patterns. Mosses, lichens, and lycophytes generally showed low REN (<20%), liverworts and conifers intermediate (40%) and monilophytes, eudicots, and monocots high (>70%). REP appeared higher in eudicots and liverworts than in mosses. Within mosses, taxa with more efficient conductance also showed higher REN. The differences in REN among clades broadly matched the degree of specialization of conducting tissues. This novel mapping of a physiological process onto the Tree of Life broadly supports the idea that the evolution of conducting tissues toward specialized phloem has aided land plants to optimize their internal nitrogen recycling. The generality of evolutionary lines in conducting tissues and nutrient resorption efficiency needs to be tested across different floras in different climatic regions with different levels of N versus P availability.
Keywords
- Bryophyte
- conducting tissue
- evolutionary specialization
- internal nutrient cycling
- lichen
- phylogeny
- pteridophyte
- senescence
- translocation
- vascular plant