Ageing and dental attrition in a medieval rural Danish population

The rate of attrition on the permanent molars may depend on culturally and economically determined conditions of living. In order to analyse the relation the probability of having entered the stages of attrition is analysed by means of logistic regression on age at death. It is shown that not all teeth continue to be worn at the same rate throughout life and that there is an association between advanced attrition and risk of dying. The rate of dental attrition does not differ much by sex but there are some indications that male teeth are worn quicker than female teeth. This greater rate of attrition might be due to greater consumption of food in males than in females. The stages of dental attrition give some information on the age at death but they are poor age indicators on their own.     

A quantitative analysis of dental attrition rates in the Santa Barbara Channel area

The dentitions of individuals from archaeological sites located along the Santa Barbara Channel were analysed using quantitative methods which allow the accurate assessment of attrition rates. Comparisons of molar wear gradients indicate that attrition rates have decreased significantly through time in the Santa Barbara Channel area.     

Lower red blood cell counts in middle-aged subjects with shorter peripheral blood leukocyte telomere length

Although telomere biology was revealed to play an important role in several hematopoietic disorders, its impact on the age-dependent dynamics of regular hematopoiesis is poorly understood. In vitro results suggest that particularly the erythropoietic capacity might be limited by critically short telomere length (TL). However, it remains unclear whether TL also affects erythropoiesis in healthy individuals in vivo. Therefore, we analyzed the associations between relevant hematopoietic parameters and peripheral blood leukocyte TL in the apparently healthy Asklepios study population, aged approximately 35-55 years (N > 2500). Our data indicate a clear positive, age and paternal age at birth adjusted, correlation between TL and red blood cell count, both in men (p < 0.001) and women (p = 0.011). This association was particularly significant in the older segment of the population (> 45 years old, both sexes: p = 0.003) and in younger men (p = 0.013), but not in younger women (p = 0.521). Further adjustment for known determinants in a general linear model revealed that peripheral blood leukocyte TL is most probably an independent predictor of red blood cell count (p < 0.001), suggesting that critical telomere shortening might also limit erythropoiesis in vivo. While negligible in a middle-aged population, the clinical consequences might be important in the elderly (e.g. in anemia of chronic disease). Further studies are required to confirm the impact of our results.     

Psychophysiologic test performance in normal twins and in a pair of identical twins with essential tremor that is suppressed by alcohol

Summary In a sample of 52 adult male twin pairs (26 MZ, 26 DZ) performance in a series of psychophysiologic tests was measured. The intraindividual variability was determined by repetitive tests in the same subjects. In a number of cases the measured parameters proved relatively stable within the same person; identical twins, however, were no more similar to one another than fraternal twins. In a pair of identical twins with autosomal-dominant essential tremor the degree of the tremor could be effectively reduced by alcohol application.This work was supported by the Deutsche Forschungsgemeinschaft within the SFB 35.     

Human telomere d[(TTAGGG)4] undergoes a conformational transition to the Na+-form upon binding with sanguinarine in presence of K+

Guanine-rich telomeric sequences fold into G-quadruplex conformation and are known to bind a variety of ligands including potential drug candidates. By means of CD spectroscopy and fluorescence lifetime measurements we demonstrate that putative anticancer therapeutic sanguinarine (SGR) exhibits two distinct interactions with human telomere d[(TTAGGG)₄] (H24) in presence of K⁺. Up to about 1:2 M ratio of H24:SGR (10 μM H24), two molecules of SGR bind H24. Above this molar ratio, SGR induces a conformational transition in H24 from the K⁺-form to the Na⁺-form. The demonstration of SGR-induced conformational transition in a G-quadruplex formed by a human telomeric sequence could provide new insights into interaction of drugs with quadruplex DNA structure.     

Longitudinal data on telomere length in leukocytes from newborn baboons support a marked drop in stem cell turnover around 1 year of age

Stem cells of various tissues are typically defined as multipotent cells with 'self-renewal' properties. Despite the increasing interest in stem cells, surprisingly little is known about the number of times stem cells can or do divide over a lifetime. Based on telomere-length measurements of hematopoietic cells, we previously proposed that the self-renewal capacity of hematopoietic stem cells is limited by progressive telomere attrition and that such cells divide very rapidly during the first year of life. Recent studies of patients with aplastic anemia resulting from inherited mutations in telomerase genes support the notion that the replicative potential of hematopoietic stem cells is directly related to telomere length, which is indirectly related to telomerase levels. To revisit conclusions about stem cell turnover based on cross-sectional studies of telomere length, we performed a longitudinal study of telomere length in leukocytes from newborn baboons. All four individual animals studied showed a rapid decline in telomere length (approximately 2-3 kb) in granulocytes and lymphocytes in the first year after birth. After 50-70 weeks the telomere length appeared to stabilize in all cell types. These observations suggest that hematopoietic stem cells, after an initial phase of rapid expansion, switch at around 1 year of age to a different functional mode characterized by a markedly decreased turnover rate.     

Correlates of reproductive success in a Caribbean village

Genealogical, demographic, and economic data collected in a rural Trinidadian village indicate that: (1) individuals with more land have more offspring, (2) males with more land have higher mating success, (3) young adults with parents resident in the village have higher reproductive success, and (4) the residence of father has a strong effect on young adult male reproductive success, but apparently has no effect on young adult female reproductive success, suggesting a gender bias in nepotism. The results indicate that there are important gender differences in the effect of resources on reproduction and in patterns of parent-offspring interaction.     

The use of CD 34(+) mobilized peripheral blood as a donor cell source does not improve chimerism after in utero hematopoietic stem cell transplantation in non-human primates

In utero hematopoietic stem cell transplantation is a therapeutic procedure that could potentially cure many developmental diseases affecting the immune and hematopoietic systems. In most clinical and experimental settings of fetal hematopoietic transplantation the level of donor cell engraftment has been low, suggesting that even in the fetus there are significant barriers to donor cell engraftment. In postnatal hematopoietic transplantation donor cells obtained from mobilized peripheral blood engraft more rapidly than cells derived from marrow. We tested the hypothesis that use of donor hematopoietic/stem cells obtained from mobilized peripheral blood would improve engraftment and the level of chimerism after in utero transplantation in non-human primates. Despite the potential competitive advantage from the use of CD 34(+) from mobilized peripheral blood, the level of chimerism was not appreciably different from a group of animals receiving marrow-derived CD 34(+) donor cells. Based on these results, it is unlikely that this single change in cell source will influence the clinical outcome of fetal hematopoietic transplantation.     

Cellular characteristics of peripheral blood lymphocytes and tumour-infiltrating lymphocytes in patients with gynaecological tumours

 Immunotherapy of gynaecological cancer with tumour-infiltrating lymphocytes (TIL) or peripheral blood lymphocytes (PBL) has become a valid treatment modality with varying degrees of success in obtaining an antitumour response. TIL consist of lymphocytes, mainly T cells and minor populations of natural killer cells or B cells. Conventional cytogenetic studies of tumour cells from patients with breast and ovarian cancer have shown multiple chromosomal abnormalities including chromosomes 7 and 12. This study was designed to analyse the surface further, as well as investigate the intracellular, characteristics of TIL by multicolour flow cytometry and the cytogenetic features by fluorescence in situ hybridization. Tumour cell, peripheral blood and TIL samples from 25 patients (15 ovarian tumours, 8 breast cancers, 1 uterine sarcoma, 1 cervical carcinoma) were analysed for their phenotype, the expression of major cytokines [interleukin-2 (IL-2), IL-4 and interferon γ (IFNγ)], their proliferation rate, their cytotoxic ability and for the presence of numerical aberrations of chromosomes 7 and 12. All the tumour cells showed a high frequency of numerical aberration in chromosomes 7 and 12, especially trisomies or tetrasomies and combined aberrations. Trisomies of both chromosomes also occured at a low percentage in TIL and PBL. Received: 20 June 1996 / Accepted: 4 January 1997     

Realistic Weight Perception and Body Size Assessment in a Racially Diverse Community Sample of Dieters

Recently, a shift in obesity treatment away from emphasizing ideal weight loss goals to establishing realistic weight loss goals has been proposed; yet, what constitutes “realistic” weight loss for different populations is not clear. This study examined notions of realistic shape and weight as well as body size assessment in a large community-based sample of African-American, Asian, Hispanic, and white men and women. Participants were 1893 survey respondents who were all dieters and primarily overweight. Groups were compared on various variables of body image assessment using silhouette ratings. No significant race differences were found in silhouette ratings, nor in perceptions of realistic shape or reasonable weight loss. Realistic shape and weight ratings by both women and men were smaller than current shape and weight but larger than ideal shape and weight ratings. Compared with male dieters, female dieters considered greater weight loss to be realistic. Implications of the findings for the treatment of obesity are discussed.     

The association of chloroplast peripheral reticulum with low photorespiration rates in a photorespiring plant species

Summary A peripheral reticulum occurs in mesophyll chloroplasts of the pentose cycle plantDactylis glomerata L. (orchardgrass). This structural feature was previously thought to occur primarily in the chloroplasts of tropical grasses and other species utilizing the C₄-dicarboxylic-acid photosynthesis pathway. Since the peripheral reticulum is seen in a selection ofD. glomerata which has a low rate of photorespiration, but not in a selection which has a high rate of photorespiration (Carlsonet al., 1971), photorespiratory rates may be dependent in part on the presence or absence of a chloroplast peripheral reticulum.Cooperative investigations of the University of Florida and the Crops Research Division, Agricultural Research Service, U.S. Department of Agriculture. Trade names are mentioned for clarity and do not imply endorsement of products by the U. S. Department of Agriculture. Journal Series No. 3813 of the Florida Agricultural Experiment Station.     

Functional defects of peripheral regulatory T lymphocytes in patients with progressive vitiligo

Auto-reactive cytotoxic T lymphocytes play a key role in the progressive loss or destruction of melanocytes in vitiligo but the mechanism underlying the loss of self-tolerance is unknown. A deregulation of regulatory T-cell biology has recently been suggested. The analysis of the suppressive effects of peripheral T regulatory cells in vitiligo patients revealed a functional defect in seven of 15 cases. This defect was strongly correlated with disease activity. The evaluation of the percentage of peripheral regulatory T lymphocytes did not reveal any intrinsic quantitative defect. Yet, a decrease in the percentage of such cells was noted in patients with progressive forms, suggesting a recruitment of regulatory T cells from the peripheral blood to the site of injury. This was further corroborated by the significant increase of Forkhead box P3 expression in the vitiliginous skin of patients. Our data support the involvement of a functional defect of peripheral regulatory T cells in the pathogenesis of vitiligo and open new possibilities to advance therapeutic approaches.     

Reproductive ecology of dioecious Siparuna (Monimiaceae) in Ecuador–a case of gall midge pollination

The reproductive ecology of the dioecious genus Siparuna , belonging to the primitive family Monimiaceae, was investigated in Ecuador. Thirteen species were studied, and species growing at high altitudes (above 500 m) were compared with species growing at lower altitudes. The genus has specialized flowers pollinated by Cecidomyiidae (Asynapta sp. and other genera) that lay eggs chiefly in male flowers since these are more easily accessible than female flowers due to their morphology. Several traits ensure that pollen transfer is accomplished: 1. long flowering of individuals and single flowers; 2. specific floral morphology (unisexuality, landing platform, restricted pore) allowing the flowers to be visited by Cecidomyiidae seeking egg-laying sites, and 3. a low number of ovules that have to be pollinated in each flower. The low number of ovules per flower results in a high pollen-ovule (P/O) ratio even though pollen production in male flowers is only moderate.
High altitude species had larger flowers, higher pollen-ovule ratios, fewer ovules per female flower, and longer periods of anthesis. Gender differences were seen in the longer functionality of female flowers; the larger numbers of male flowers produced; and the average diameter at breast height (DBH) biased for one of the two sexes depending on the species investigated, with no clear trend in the size distributions of individuals of both sexes. Sex ratios departed significantly from unity both to male and female bias but usually were in favour of males. There were no general differences in the ratio of functional male to female flowers at the time of observation nor in the sizes of male and female flowers. The evolution of unisexual flowers in Siparuna can be explained as a result of the differential predation by larvae: unimportant in male flowers, destructive if occurring in female flowers.     

Gender differences in landmark learning for virtual navigation: the role of distance to a goal

We used a new virtual program in two experiments to prepare subjects to perform the Morris water task (www.nesplora.com). The subjects were Psychology students; they were trained to locate a safe platform amidst the presence of four pinpoint landmarks spaced around the edge of the pool (i.e., two landmarks relatively near the platform and two landmarks relatively distant away from it). At the end of the training phase, we administered one test trial without the platform and recorded the amount of time that the students had spent in the platform quadrant. In Experiment 1, we conducted the test trial in the presence of one or two of the distant landmarks. When only one landmark was present during testing, performance fell to chance. However, the men outperformed the women when the two distant landmarks were both present. Experiment 2 replicated the previous results and extended it by showing that no sex differences exist when the searching process is based on the near landmarks. Both the men and the women had similarly good performances when the landmarks were present both individually and together. When present together, an addition effect was found. Far landmark tests favor configural learning processes, whereas near landmark tests favor elemental learning. Our findings suggest that other factors in addition to the use of directional cues can underlie the sex differences in the spatial learning process. Thus, we expand upon previous research in the field.     

Specific association of a small protein with the telomeric DNA-protein complex during the onset of leaf senescence in Arabidopsis thaliana

Telomeres and their changes in length throughout the life span of cells have been intensively investigated in different organisms. Telomere length is assumed to control replicative senescence in mammalian cells. However, only very few data are available on the developmental dynamics of plant telomeres. Here, changes of telomere length and DNA-protein structure of Arabidopsis thaliana telomeres were analysed in different stages of development, with the main focus resting on the transition from pre-senescent to senescent leaves. The lengths of the telomeres, ranging from ca. 2.0 to 6.5 kb, do not significantly change during plant development indicating that telomere length is not involved in differentiation and replicative senescence nor in post-mitotic senescence of A. thaliana. In dedifferentiated cultured cells a slight increase in length can be determined. The nucleoprotein structure of the telomeric DNA was investigated by gel mobility shift assays, with synthetic oligonucleotides and nuclear protein extracts derived from four defined stages of post-mitotic leaf senescence. In all four stages, a highly salt-resistant DNA-protein complex was formed with the double-stranded as well as with the single-stranded G-rich telomeric DNA. An additional DNA-protein complex was identified in nuclear protein extracts isolated from plants in the transition stage from pre-senescence to senescence. The protein components of the DNA-protein complexes were analysed on native PAGE and SDS-PAGE gels. A protein of 67 kDa (ATBP1) bound to the telomeric DNA in all developmental stages. An additional protein of merely 22 kDa (ATBP2) was associated via protein-protein interaction with ATBP1 to form a higher-order complex exclusively during the onset of senescence. DNA interaction of this higher-order protein complex seems to be restricted to double-stranded telomeric DNA. The defined period of ATBP1/ATBP2 complex formation with the telomeric DNA probably indicates that ATBP2 is involved in the onset of post-mitotic leaf senescence by either disturbing an established or establishing an additional function exhibited by the telomeres in the interphase nuclei.     

Association of maternal and nutrient supply line factors with DNA methylation at the imprinted IGF2/H19 locus in multiple tissues of newborn twins

Epigenetic events are crucial for early development, but can be influenced by environmental factors, potentially programming the genome for later adverse health outcomes. The insulin-like growth factor 2 (IGF2)/H19 locus is crucial for prenatal growth and the epigenetic state at this locus is environmentally labile. Recent studies have implicated maternal factors, including folate intake and smoking, in the regulation of DNA methylation at this locus, although data are often conflicting in the direction and magnitude of effect. Most studies have focused on single tissues and on one or two differentially-methylated regions (DMRs) regulating IGF2/H19 expression. In this study, we investigated the relationship between multiple shared and non-shared gestational/maternal factors and DNA methylation at four IGF2/H19 DMRs in five newborn cell types from 67 pairs of monozygotic and 49 pairs of dizygotic twins. Data on maternal and non-shared supply line factors were collected during the second and third trimesters of pregnancy and DNA methylation was measured via mass spectrometry using Sequenom MassArray EpiTyper analysis. Our exploratory approach showed that the site of umbilical cord insertion into the placenta in monochorionic twins has the strongest positive association with methylation in all IGF2/H19 DMRs (p < 0.05). Further, evidence for tissue- and locus-specific effects were observed, emphasizing that responsiveness to environmental exposures in utero cannot be generalized across genes and tissues, potentially accounting for the lack of consistency in previous findings. Such complexity in responsiveness to environmental exposures in utero has implications for all epigenetic studies investigating the developmental origins of health and disease.     

Biomonitoring of DNA damage in peripheral blood lymphocytes of subjects with dental restorative fillings

Dental fillings provide a major iatrogenic exposure to xenobiotic compounds due to the high prevalence of surface restorations in developed countries. Experimental data suggest that both amalgams, which contain mercury, and resin-based dental materials cause an impairment of the cellular pro- and anti-oxidant redox balance. The aim of this study was to assess the potential genotoxicity of dental restorative compounds in peripheral blood lymphocytes of young exposed subjects compared with controls. The study examined, by use of the comet assay, 68 carefully selected subjects taking into account the major known confounding factors. In the 44 exposed subjects, the mean numbers of restored surfaces was 3.0 and 3.8 in males and females, respectively. Tail length, percentage of DNA in the tail, tail moment or Olive tail moment were twofold higher in the exposed group than in unexposed controls, with significant differences. No significant difference was observed between amalgam and composite fillings. Furthermore, as shown by multivariate analysis, the association between dental fillings and DNA damage was enhanced by the number of fillings and by the exposure time. Among the lifestyle variables, a moderate physical activity showed a protective effect, being inversely correlated to the DNA damage parameters evaluated. On the whole, the use of DNA-migration allowed us to detect for the first time the potential adverse impact on human health of both kinds of dental filling constituents, the amalgams and the methacrylates. The main mechanism underlying the genotoxicity of dental restorative materials of various nature may be ascribed to the ability of both amalgams and methacrylates to trigger the generation of cellular reactive oxygen species, able to cause oxidative DNA lesions.     

Absence of association of a single-nucleotide polymorphism in the TERT-CLPTM1L locus with age-related phenotypes in a large multicohort study: the HALCyon programme

Several age-related traits are associated with shorter telomeres, the structures that cap the end of linear chromosomes. A common polymorphism near the telomere maintenance gene TERT has been associated with several cancers, but relationships with other aging traits such as physical capability have not been reported. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women aged between 44 and 90 years from nine UK cohorts were genotyped for the single-nucleotide polymorphism (SNP) rs401681. We then investigated relationships between the SNP and 30 age-related phenotypes, including cognitive and physical capability, blood lipid levels and lung function, pooling within-study genotypic effects in meta-analyses. No significant associations were found between the SNP and any of the cognitive performance tests (e.g. pooled beta per T allele for word recall z-score = 0.02, 95% CI: -0.01 to 0.04, P-value = 0.12, n = 18,737), physical performance tests (e.g. pooled beta for grip strength = -0.02, 95% CI: -0.045 to 0.006, P-value = 0.14, n = 11,711), blood pressure, lung function or blood test measures. Similarly, no differences in observations were found when considering follow-up measures of cognitive or physical performance after adjusting for its measure at an earlier assessment. The lack of associations between SNP rs401681 and a wide range of age-related phenotypes investigated in this large multicohort study suggests that while this SNP may be associated with cancer, it is not an important contributor to other markers of aging.     

Frequency analysis of tumor-reactive cytotoxic T lymphocytes in peripheral blood of a melanoma patient vaccinated with autologous tumor cells

A limiting-dilution assay was developed and used to determine the frequency of autologous tumor-reactive cytotoxic T lymphocytes (CTL) in peripheral blood of a melanoma patient MZ2, who has been free of detectable disease since several years. In this patient, the frequencies of tumor-reactive CTL spontaneously varied only by a factor of 1.5. After vaccinations with autologous mutagenized and lethally irradiated tumor cells a two- to tenfold increase in frequencies of tumor-reactive CTL was found within the first 2 weeks. Thereafter, CTL frequencies returned to values measured prior to vaccinations. We conclude, that the limiting-dilution assay applied in this study can detect changes in the T cell response to autologous tumor cells. The frequency of tumor-reactive CTL determined with this approach can serve as an immunological parameter for monitoring the T cell response to autologous tumor cells in individual cancer patients receiving tumor cell vaccinations.