A comparison of subadult skeletal and dental development based on living and deceased samples.

OBJECTIVES: A fundamental assumption in biological anthropology is that living individuals will present with different growth than non-survivors of the same population. The aim is to address the question of whether growth and development data of non-survivors are reflective of the biological consequences of selective mortality and/or stress. MATERIALS AND METHODS: The study compares dental development and skeletal growth collected from radiographic images of contemporary samples of living and deceased individuals from the United States (birth to 20 years) and South Africa (birth to 12 years). Further evaluation of deceased individuals is used to explore differential patterns among manners of death (MOD). RESULTS: Results do not show any significant differences in skeletal growth or dental development between living and deceased individuals. However, in the South African deceased sample the youngest individuals exhibited substantially smaller diaphyseal lengths than the living sample, but by 2 years of age the differences were negligible. In the US sample, neither significant nor substantial differences were found in dental development or diaphyseal length according to MOD and age (>2 years of age), though some long bones in individuals <2 years of age did show significant differences. No significant differences were noted in diaphyseal length according to MOD and age in the SA sample. DISCUSSION: The current findings refute the idea that contemporary deceased and living individuals would present with differential growth and development patterns through all of ontogeny as well as the assumptions linking short stature, poor environments, and MOD.

A Test of Age Estimation Methods on Impacted Third Molars in Males.

This study tests the relationship between third molar impaction and its concomitant effect on age estimation methods. Data were collected on radiographs of males analyzed in the Defense POW/MIA Accounting Agency Laboratory (n = 114). Radiographs of skeletonized individuals were scored for dental development, and age was assigned based on the appropriate ancestry-based method. Differences between identified age and estimated dental age were assessed to determine whether molar impaction affected root development and age estimations. Results indicate that impacted teeth tend to be underdeveloped and result in age estimates that are too low. While these results are of note to anthropologists and odontologists performing dental age estimates, more work is needed to explore the effect of impaction on development among a more diverse sample.

Impact of population-specific dental development on age estimation using dental atlases.

OBJECTIVES: The steady development and subsequent eruption of the dentition is particularly useful for the estimation of age in juveniles. There are few studies that examine and test methods on a population-diverse sample. Our goal is to test the Ubelaker () and London Atlas (2010) dental charts on a sample representing several different population backgrounds to infer if refinement for population-specific standards should be developed. MATERIALS AND METHODS: The first and second authors examined panoramic radiographs of 335 individuals from the James K. Economides Orthodontic Collection blind to chronological age, sex, and ancestry and scored using both dental atlases. RESULTS: The age of Native Americans and African Americans was generally overestimated, suggesting faster rates of development. European Americans and New Mexico Hispanics, while not always showing the highest success rates, generally were closer to the correct age than other ancestry groups. The overall success rate for Ubelaker () was 80.00% for both observers, while the London Atlas was significantly lower at approximately 21.79-23.28%. Accuracy rates did not differ significantly between ancestry groups, though patterns were evident regarding under- or over-estimation of age. DISCUSSION: The present study demonstrates that incorrect age estimations were typically still within 1.5 years of the actual age. Ubelaker () had higher rates of success due to broader age ranges. The results suggest that though accuracy rates did not significantly differ, different developmental rates may affect age estimates and population-specific standards should be considered for known-ancestry individuals, while aging standards constructed from a diverse sample should be utilized for unknown-ancestry cases.

Anti-inflammatory and neuroactive properties of selected fruit extracts.

Epidemiological evidence supports inverse associations between fruit and vegetable intake and incidence of cardiovascular disease and neurodegeneration. Dietary botanicals with salient health benefits include berries and leafy vegetables. Molecular pharmacology research has ascribed these benefits primarily to phenolic constituents and antioxidant activity. The current investigation sought to eluicidate pharmacologic activity of two novel preparations of berry and spinach extracts in vitro. Blueberry and cranberry exhibited the greatest antioxidant activity. In a dose-dependent manner, a proprietary mixture of cranberry and blueberry extracts inhibited inhibitor of κB kinase ß, a central node in inflammatory signal transduction. A proprietary mixture of blueberry, strawberry, and spinach extracts inhibited prolyl endopeptidase, a regulator of central neuropeptide stability and an emerging therapeutic target in neurology and psychiatry. These results indicate specific molecular targets of blended dietary plants with potential relevance to inflammation and neurological health.

Retinoic acid mediates long-paced oscillations in retinoid receptor activity: evidence for a potential role for RIP140.

BACKGROUND: Mechanisms that underlie oscillatory transcriptional activity of nuclear receptors (NRs) are incompletely understood. Evidence exists for rapid, cyclic recruitment of coregulatory complexes upon activation of nuclear receptors. RIP140 is a NR coregulator that represses the transactivation of agonist-bound nuclear receptors. Previously, we showed that RIP140 is inducible by all-trans retinoic acid (RA) and mediates limiting, negative-feedback regulation of retinoid signaling. METHODOLOGY AND FINDINGS: Here we report that in the continued presence of RA, long-paced oscillations of retinoic acid receptor (RAR) activity occur with a period ranging from 24 to 35 hours. Endogenous expression of RIP140 and other RA-target genes also oscillate in the presence of RA. Cyclic retinoid receptor transactivation is ablated by constitutive overexpression of RIP140. Further, depletion of RIP140 disrupts cyclic expression of the RA target gene HOXA5. Evidence is provided that RIP140 may limit RAR signaling in a selective, non-redundant manner in contrast to the classic NR coregulators NCoR1 and SRC1 that are not RA-inducible, do not cycle, and may be partially redundant in limiting RAR activity. Finally, evidence is provided that RIP140 can repress and be induced by other nuclear receptors in a manner that suggests potential participation in other NR oscillations. CONCLUSIONS AND SIGNIFICANCE: We provide evidence for novel, long-paced oscillatory retinoid receptor activity and hypothesize that this may be paced in part, by RIP140. Oscillatory NR activity may be involved in mediating hormone actions of physiological and pathological importance.

Selective repression of retinoic acid target genes by RIP140 during induced tumor cell differentiation of pluripotent human embryonal carcinoma cells.

BACKGROUND: The use of retinoids as anti-cancer agents has been limited due to resistance and low efficacy. The dynamics of nuclear receptor coregulation are incompletely understood. Cell-and context-specific activities of nuclear receptors may be in part due to distinct coregulator complexes recruited to distinct subsets of target genes. RIP140 (also called NRIP1) is a ligand-dependent corepressor that is inducible with retinoic acid (RA). We had previously shown that RIP140 limits RA induced tumor cell differentiation of embryonal carcinoma; the pluriopotent stem cells of testicular germ cell tumors. This implies that RIP140 represses key genes required for RA-mediated tumor cell differentiation. Identification of these genes would be of considerable interest. RESULTS: To begin to address this issue, microarray technology was employed to elucidate in a de novo fashion the global role of RIP140 in RA target gene regulation of embryonal carcinoma. Subclasses of genes were affected by RIP140 in distinct manners.Interestingly, approximately half of the RA-dependent genes were unaffected by RIP140. Hence, RIP140 appears to discriminate between different classes of RA target genes. In general, RIP140-dependent gene expression was consistent with RIP140 functioning to limit RA signaling and tumor cell differentiation. Few if any genes were regulated in a manner to support a role for RIP140 in "active repression". We also demonstrated that RIP140 silencing sensitizes embryonal carcinoma cells to low doses of RA. CONCLUSION: Together the data demonstrates that RIP140 has profound effects on RA-mediated gene expression in this cancer stem cell model. The RIP140-dependent RA target genes identified here may be particularly important in mediating RA-induced tumor cell differentiation and the findings suggest that RIP140 may be an attractive target to sensitize tumor cells to retinoid-based differentiation therapy. We discuss these data in the context of proposed models of RIP140-mediated repression.

Positive and negative regulation of deltaN-p63 promoter activity by p53 and deltaN-p63-alpha contributes to differential regulation of p53 target genes.

Mammary epithelial regeneration implies the existence of cellular progenitors with retained replicative capacity, prolonged lifespan and developmental potency. Evidence exists that deltaN-p63 isoforms preserve these features by modulating p53 activity in basal epithelia. deltaN-p63 mRNA levels decline at the onset of differentiation suggesting that its transcriptional regulation may contribute to the initiation of differentiation. To study transcriptional regulation of deltaN-p63, a 10.3 kbp fragment containing the deltaN-p63 promoter was isolated. We report here that deltaN-p63 is a positive and negative transcriptional target of p53 and deltaN-p63-alpha, respectively. Disruption of p53 activity or expression abolishes the expression of deltaN-p63-alpha. This regulation is mediated by a p53-binding element sufficient to confer these activities to a heterologous promoter. Chromatin immune-precipitation indicates that, in asynchronously growing cells, p53 occupies this element. In response to DNA damage, deltaN-p63-alpha is recruited to this element as transcription of deltaN-p63 declines. Disruption of deltaN-p63-alpha expression had differential effects on the transcriptional regulation of several p53-target genes. These findings indicate that p53 contributes to the preservation of basal epithelia by driving the expression of deltaN-p63 isoforms. These studies also suggest that in response to genotoxic stress, deltaN-p63-alpha mediates the silencing of its own promoter thereby altering the pattern of p53-target gene expression.

Effects of ketamine-xylazine and isoflurane on insulin sensitivity in dehydroepiandrosterone sulfate-treated minipigs (Sus scrofa domestica).

Isoflurane and ketamine-xylazine (KX) combinations are widely used veterinary anesthetics, KX being the particularly common agent for immobilizing swine. Results of previous studies indicate that KX and xylazine suppress insulin release. The steroid hormones, dehydroepiandrosterone (DHEA) and its sulfated form, dehydroepiandrosterone-sulfate (DHEAS), have variable effects on insulin sensitivity in animals. We evaluated the effect of DHEAS on plasma glucose and insulin concentrations in female Yucatan swine under KX and isoflurane anesthesia. A 2 x 2 factorial design was used. Twenty-four 17-week-old gilts were randomly assigned to receive vehicle (placebo) or DHEAS as part of an ongoing study. The KX was given intramuscularly to all animals prior to blood sample collection at weeks two and four. At week three, all animals received isoflurane by inhalation. During KX anesthesia, mean insulin concentration in DHEAS-treated and control groups approximated half the postisoflurane values (P < 0.001). While under isoflurane, the DHEAS group had significantly higher mean plasma insulin concentration and mean insulin-to-glucose ratio, compared with values for controls (P < 0.05). These findings are consistent with changes in insulin values following DHEAS treatment observed previously in nonanesthetized swine. The effect of DHEAS treatment was absent in animals under KX anesthesia. These results suggest that KX significantly decreases plasma insulin concentration and blunts DHEAS-associated insulin resistance in female minipigs.

Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships.

Flavonoids are a class of secondary plant phenolics with significant antioxidant and chelating properties. In the human diet, they are most concentrated in fruits, vegetables, wines, teas and cocoa. Their cardioprotective effects stem from the ability to inhibit lipid peroxidation, chelate redox-active metals, and attenuate other processes involving reactive oxygen species. Flavonoids occur in foods primarily as glycosides and polymers that are degraded to variable extents in the digestive tract. Although metabolism of these compounds remains elusive, enteric absorption occurs sufficiently to reduce plasma indices of oxidant status. The propensity of a flavonoid to inhibit free-radical mediated events is governed by its chemical structure. Since these compounds are based on the flavan nucleus, the number, positions, and types of substitutions influence radical scavenging and chelating activity. The diversity and multiple mechanisms of flavonoid action, together with the numerous methods of initiation, detection and measurement of oxidative processes in vitro and in vivo offer plausible explanations for existing discrepancies in structure-activity relationships. Despite some inconsistent lines of evidence, several structure-activity relationships are well established in vitro. Multiple hydroxyl groups confer upon the molecule substantial antioxidant, chelating and prooxidant activity. Methoxy groups introduce unfavorable steric effects and increase lipophilicity and membrane partitioning. A double bond and carbonyl function in the heterocycle or polymerization of the nuclear structure increases activity by affording a more stable flavonoid radical through conjugation and electron delocalization. Further investigation of the metabolism of these phytochemicals is justified to extend structure-activity relationships (SAR) to preventive and therapeutic nutritional strategies.