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Sample records for repeat length ages

  1. Age, CAG repeat length, and clinical progression in Huntington's disease.

    Science.gov (United States)

    Rosenblatt, Adam; Kumar, Brahma V; Mo, Alisa; Welsh, Claire S; Margolis, Russell L; Ross, Christopher A

    2012-02-01

    The objective of this study was to further explore the effect of CAG repeat length on the rate of clinical progression in patients with Huntington's disease. The dataset included records for 569 subjects followed prospectively at the Baltimore Huntington's Disease Center. Participants were seen for a mean of 7.1 visits, with a mean follow-up of 8.2 years. Subjects were evaluated using the Quantified Neurologic Examination and its Motor Impairment subscale, the Mini-Mental State Examination, and the Huntington's disease Activities of Daily Living Scale. By itself, CAG repeat length showed a statistically significant but small effect on the progression of all clinical measures. Contrary to our previous expectations, controlling for age of onset increased the correlation between CAG repeat length and progression of all variables by 69% to 159%. Graphical models further supported the idea that individuals with smaller triplet expansions experience a more gradual decline. CAG repeat length becomes an important determinant of clinical prognosis when accounting for age of onset. This suggests that the aging process itself influences clinical outcomes in Huntington's disease. Inconsistent results in prior studies examining CAG repeat length and progression may indeed reflect a lack of age adjustment.

  2. A Familial Factor Independent of CAG Repeat Length Influences Age at Onset of Machado-Joseph Disease

    OpenAIRE

    DeStefano, Anita L.; Cupples, L. Adrienne; Maciel, Patricia; Gaspar, Claudia; Radvany, Joao; Dawson, David M.; Sudarsky, Lewis; Corwin, Lee; Coutinho, Paula; MacLeod, Patrick; Sequeiros, Jorge; Rouleau, Guy A.; Farrer, Lindsay A.

    1996-01-01

    Machado-Joseph disease (MJD) is a late-onset, progressive, neurodegenerative disorder caused by the expansion of an unstable trinucleotide (CAG) repeat sequence in a novel gene (MJD1) on chromosome 14. Previous studies showed that age at onset is negatively correlated with the number of CAG repeat units, but only part of the variation in onset age is explained by CAG repeat length. Ages at onset and CAG repeat lengths of 136 MJD patients from 23 kindreds of Portuguese descent were analyzed, t...

  3. DRPLA transgenic mouse substrains carrying single copy of full-length mutant human DRPLA gene with variable sizes of expanded CAG repeats exhibit CAG repeat length- and age-dependent changes in behavioral abnormalities and gene expression profiles.

    Science.gov (United States)

    Suzuki, Kazushi; Zhou, Jiayi; Sato, Toshiya; Takao, Keizo; Miyagawa, Tsuyoshi; Oyake, Mutsuo; Yamada, Mitunori; Takahashi, Hitoshi; Takahashi, Yuji; Goto, Jun; Tsuji, Shoji

    2012-05-01

    Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant progressive neurodegenerative disorder with intellectual deterioration and various motor deficits including ataxia, choreoathetosis, and myoclonus, caused by an abnormal expansion of CAG repeats in the DRPLA gene. Longer expanded CAG repeats contribute to an earlier age of onset, faster progression, and more severe neurological symptoms in DRPLA patients. In this study, we have established DRPLA transgenic mouse lines (sublines) harboring a single copy of the full-length mutant human DRPLA gene carrying various lengths of expanded CAG repeats (Q76, Q96, Q113, and Q129), which have clearly shown motor deficits and memory disturbance whose severity increases with the length of expanded CAG repeats and age, and successfully replicated the CAG repeat length- and age-dependent features of DRPLA patients. Neuronal intranuclear accumulation of the mutant DRPLA protein has been suggested to cause transcriptional dysregulation, leading to alteration in gene expression and neuronal dysfunction. In this study, we have conducted a comprehensive analysis of gene expression profiles in the cerebrum and cerebellum of transgenic mouse lines at 4, 8, and 12 weeks using multiple microarray platforms, and demonstrated that both the number and expression levels of the altered genes are highly dependent on CAG repeat length and age in both brain regions. Specific groups of genes and their function categories were identified by further agglomerative cluster analysis and gene functional annotation analysis. Calcium signaling and neuropeptide signaling, among others, were implicated in the pathophysiology of DRPLA. Our study provides unprecedented CAG-repeat-length-dependent mouse models of DRPLA, which are highly valuable not only for elucidating the CAG-repeat-length-dependent pathophysiology of DRPLA but also for developing therapeutic strategies for DRPLA.

  4. The relationship between CAG repeat length and age of onset differs for Huntington's disease patients with juvenile onset or adult onset.

    Science.gov (United States)

    Andresen, J Michael; Gayán, Javier; Djoussé, Luc; Roberts, Simone; Brocklebank, Denise; Cherny, Stacey S; Cardon, Lon R; Gusella, James F; MacDonald, Marcy E; Myers, Richard H; Housman, David E; Wexler, Nancy S

    2007-05-01

    Age of onset for Huntington's disease (HD) varies inversely with the length of the disease-causing CAG repeat expansion in the HD gene. A simple exponential regression model yielded adjusted R-squared values of 0.728 in a large set of Venezuelan kindreds and 0.642 in a North American, European, and Australian sample (the HD MAPS cohort). We present evidence that a two-segment exponential regression curve provides a significantly better fit than the simple exponential regression. A plot of natural log-transformed age of onset against CAG repeat length reveals this segmental relationship. This two-segment exponential regression on age of onset data increases the adjusted R-squared values by 0.012 in the Venezuelan kindreds and by 0.035 in the HD MAPS cohort. Although the amount of additional variance explained by the segmental regression approach is modest, the two slopes of the two-segment regression are significantly different from each other in both the Venezuelan kindreds [F(2, 439) = 11.13, P= 2 x 10(-5)] and in the HD MAPS cohort [F(2, 688) = 38.27, P= 2 x 10(-16)]. In both populations, the influence of each CAG repeat on age of onset appears to be stronger in the adult-onset range of CAG repeats than in the juvenile-onset range.

  5. Discrepancies in reporting the CAG repeat lengths for Huntington's disease

    DEFF Research Database (Denmark)

    Quarrell, Oliver W; Handley, Olivia; O'Donovan, Kirsty

    2011-01-01

    Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original...

  6. Telomere length variations in aging and age-related diseases.

    Science.gov (United States)

    Rizvi, Saliha; Raza, Syed Tasleem; Mahdi, Farzana

    2014-01-01

    Telomeres are gene sequences present at chromosomal ends and are responsible for maintaining genome integrity. Telomere length is maximum at birth and decreases progressively with advancing age and thus is considered as a biomarker of chronological aging. This age associated decrease in the length of telomere is linked to various ageing associated diseases like diabetes, hypertension, Alzheimer's disease, cancer etc. and their associated complications. Telomere length is a result of combined effect of oxidative stress, inflammation and repeated cell replication on it, and thus forming an association between telomere length and chronological aging and related diseases. Thus, decrease in telomere length was found to be important in determining both, the variations in longevity and age-related diseases in an individual. Ongoing and progressive research in the field of telomere length dynamics has proved that aging and age-related diseases apart from having a synergistic effect on telomere length were also found to effect telomere length independently also. Here a short description about telomere length variations and its association with human aging and age-related diseases is reviewed.

  7. Striatal and extrastriatal atrophy in Huntington's disease and its relationship with length of the CAG repeat

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    H.H. Ruocco

    2006-08-01

    Full Text Available Huntington's disease (HD is an autosomal dominant neurodegenerative disorder that affects the striatum most severely. However, except for juvenile forms, relative preservation of the cerebellum has been reported. The objective of the present study was to perform MRI measurements of caudate, putamen, cerebral, and cerebellar volumes and correlate these findings with the length of the CAG repeat and clinical parameters. We evaluated 50 consecutive patients with HD using MRI volumetric measurements and compared them to normal controls. Age at onset of the disease ranged from 4 to 73 years (mean: 43.1 years. The length of the CAG repeat ranged from 40 to 69 (mean: 47.2 CAG. HD patients presented marked atrophy of the caudate and putamen, as well as reduced cerebellar and cerebral volumes. There was a significant correlation between age at onset of HD and length of the CAG repeat, as well as clinical disability and age at onset. The degree of basal ganglia atrophy correlated with the length of the CAG repeat. There was no correlation between cerebellar or cerebral volume and length of the CAG repeat. However, there was a tendency to a positive correlation between duration of disease and cerebellar atrophy. While there was a negative correlation of length of the CAG repeat with age at disease onset and with striatal degeneration, its influence on extrastriatal atrophy, including the cerebellum, was not clear. Extrastriatal atrophy occurs later in HD and may be related to disease duration.

  8. Striatal and extrastriatal atrophy in Huntington's disease and its relationship with length of the CAG repeat.

    Science.gov (United States)

    Ruocco, H H; Lopes-Cendes, I; Li, L M; Santos-Silva, M; Cendes, F

    2006-08-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that affects the striatum most severely. However, except for juvenile forms, relative preservation of the cerebellum has been reported. The objective of the present study was to perform MRI measurements of caudate, putamen, cerebral, and cerebellar volumes and correlate these findings with the length of the CAG repeat and clinical parameters. We evaluated 50 consecutive patients with HD using MRI volumetric measurements and compared them to normal controls. Age at onset of the disease ranged from 4 to 73 years (mean: 43.1 years). The length of the CAG repeat ranged from 40 to 69 (mean: 47.2 CAG). HD patients presented marked atrophy of the caudate and putamen, as well as reduced cerebellar and cerebral volumes. There was a significant correlation between age at onset of HD and length of the CAG repeat, as well as clinical disability and age at onset. The degree of basal ganglia atrophy correlated with the length of the CAG repeat. There was no correlation between cerebellar or cerebral volume and length of the CAG repeat. However, there was a tendency to a positive correlation between duration of disease and cerebellar atrophy. While there was a negative correlation of length of the CAG repeat with age at disease onset and with striatal degeneration, its influence on extrastriatal atrophy, including the cerebellum, was not clear. Extrastriatal atrophy occurs later in HD and may be related to disease duration.

  9. Linking SNPs to CAG repeat length in Huntington's disease patients.

    Science.gov (United States)

    Liu, Wanzhao; Kennington, Lori A; Rosas, H Diana; Hersch, Steven; Cha, Jang-Ho; Zamore, Phillip D; Aronin, Neil

    2008-11-01

    Allele-specific silencing using small interfering RNAs targeting heterozygous single-nucleotide polymorphisms (SNPs) is a promising therapy for human trinucleotide repeat diseases such as Huntington's disease. Linking SNP identities to the two HTT alleles, normal and disease-causing, is a prerequisite for allele-specific RNA interference. Here we describe a method, SNP linkage by circularization (SLiC), to identify linkage between CAG repeat length and nucleotide identity of heterozygous SNPs using Huntington's disease patient peripheral blood samples.

  10. Long-term disability and prognosis in dentatorubral-pallidoluysian atrophy: a correlation with CAG repeat length.

    Science.gov (United States)

    Hasegawa, Arika; Ikeuchi, Takeshi; Koike, Ryoko; Matsubara, Nae; Tsuchiya, Miyuki; Nozaki, Hiroaki; Homma, Atsushi; Idezuka, Jiro; Nishizawa, Masatoyo; Onodera, Osamu

    2010-08-15

    Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder caused by CAG repeat expansion. Previous studies demonstrated that the onset of DRPLA is closely associated with CAG repeat length. However, the natural history of DRPLA has not yet been evaluated. We here retrospectively investigated the factors that determine the disease milestones and prognosis in 183 Japanese patients genetically diagnosed with DRPLA. We determined the age at onset, age at which each of the subsequent clinical manifestations appeared, age at becoming wheelchair-bound, and age at death. Kaplan-Meier analysis revealed that the patients with CAG repeats larger than the median length of 65 repeats developed each of the clinical features of DRPLA at a younger age than those with repeats. The patients became wheelchair-bound at a median age of 33 years (n = 61; range, 3-77 years) and died at a median age of 49 years (n = 23; range, 18-80 years). The ages at becoming wheelchair-bound and at death strongly correlated with the expanded CAG repeat length. Moreover, the patients with >or=65 CAG repeats showed a more severe long-term disability and a poorer prognosis. In contrast, the rate of progression after the onset did not correlate with CAG repeat length. The CAG repeat length may have a considerable effect on not only the disease onset but also the disease milestones and prognosis in DRPLA patients. These effects of CAG repeat length may be relevant in designing future clinical therapeutic trials.

  11. Low-Normal FMR1 CGG Repeat Length: Phenotypic Associations

    Directory of Open Access Journals (Sweden)

    Marsha eMailick

    2014-09-01

    Full Text Available This population-based study investigates genotype-phenotype correlations of low-normal CGG repeats in the fragile X mental retardation 1 (FMR1 gene. FMR1 plays an important role in brain development and function, and encodes FMRP (fragile X mental retardation protein, an RNA-binding protein that regulates protein synthesis impacting activity-dependent synaptic development and plasticity. Most past research has focused on CGG premutation expansions (41 to 200 CGG repeats and on fragile X syndrome (200+ CGG repeats, with considerably less attention on the other end of the spectrum of CGG repeats. Using existing data, older adults with 23 or fewer CGG repeats (2 SDs below the mean were compared with age-peers who have normal numbers of CGGs (24-40 with respect to cognition, mental health, cancer, and having children with disabilities. Men (n = 341 with an allele in the low-normal range and women (n = 46 with two low-normal alleles had significantly more difficulty with their memory and ability to solve day to day problems. Women with both FMR1 alleles in the low-normal category had significantly elevated odds of feeling that they need to drink more to get the same effect as in the past. These women also had two and one-half times the odds of having had breast cancer and four times the odds of uterine cancer. Men and women with low-normal CGGs had higher odds of having a child with a disability, either a developmental disability or a mental health condition. These findings are in line with the hypothesis that there is a need for tight neuronal homeostatic control mechanisms for optimal cognitive and behavioral functioning, and more generally that low numbers as well as high numbers of CGG repeats may be problematic for health.

  12. CAG repeat length in androgen receptor gene and male infertility in Egyptian patients.

    Science.gov (United States)

    Mosaad, Y M; Shahin, D; Elkholy, A A-M; Mosbah, A; Badawy, W

    2012-02-01

    The CAG repeat and its association with infertility has been debatable. Therefore, this study was planned to assess the distribution of CAG repeat expansion in Egyptian patients and to investigate its association with male infertility. Forty-five infertile men were eligible for the study in addition to 20 aged-matched fertile males as control. Semen analysis, scrotal sonography, assay of serum testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH), and determination of the CAG repeat number within exon 1 of the androgen receptor (AR) gene were carried out. Statistically significant difference was found between infertile and control groups regarding sperm count, sperm motility, serum FSH level and CAG repeats (P CAG repeats (P = 1.0) was found between oligozoospermic and asthenospermic groups; negative correlation was found between CAG repeat length and sperm count, and a positive correlation was found between CAG repeat length and serum FSH (P CAG repeat may be associated with lower AR function with derangement of sperm production, and this may contribute to male infertility in Egyptian men.

  13. Relationship between CAG repeat length and brain volume in premanifest and early Huntington's disease.

    Science.gov (United States)

    Henley, Susie M D; Wild, Edward J; Hobbs, Nicola Z; Scahill, Rachael I; Ridgway, Gerard R; Macmanus, David G; Barker, Roger A; Fox, Nick C; Tabrizi, Sarah J

    2009-02-01

    Huntington's disease (HD) is caused by an expanded CAG repeat on the gene encoding for the protein huntingtin. There are conflicting findings about the extent to which repeat length predicts signs of the disease or severity of disease progression in adults. This study examined the relationship between CAG repeat length and brain volume in a large cohort of pre- and post-motor onset HD gene carriers, using voxel-based morphometry (VBM), an approach which allowed us to investigate the whole brain without defining a priori regions of interest. We also used VBM to examine group differences between 20 controls, 21 premanifest, and 40 early HD subjects. In the 61 mutation-positive subjects higher CAG repeat length was significantly associated with reduced volume of the body of the caudate nucleus bilaterally, left putamen, right insula, right parahippocampal gyrus, right anterior cingulate, and right occipital lobe, after correcting for age. The group contrasts showed significant reduction in grey matter volume in the early HD group relative to controls in widespread cortical as well as subcortical areas but there was no evidence of difference between controls and premanifest subjects. Overall we have demonstrated that increased CAG repeat length is associated with atrophy in extra-striatal as well as striatal regions, which has implications for the monitoring of disease-modifying therapies in the condition.

  14. TPR repeats and ELTR pattern: length variation as a function evolution mechanism.

    Science.gov (United States)

    Yang, Ke-Qian

    2007-12-01

    TPR repeat was originally defined as a 34 amino acid structural repeat (TPR-34). Equal length tandem repeats (ELTR) was proposed to represent the ancestral repeat pattern. Length polymorphism of TPR repeats was analyzed using PATTINPROT, two new versions of TPR repeat of 40 and 42 amino acids were identified. These 'long' TPRs endow new functional capacities to the resulting proteins. A strong correlation between varied lengths and new functions supports the hypothesis that length variation is an underlying mechanism for the function evolution of repeat containing proteins.

  15. HD CAGnome: a search tool for huntingtin CAG repeat length-correlated genes.

    Directory of Open Access Journals (Sweden)

    Ekaterina I Galkina

    Full Text Available BACKGROUND: The length of the huntingtin (HTT CAG repeat is strongly correlated with both age at onset of Huntington's disease (HD symptoms and age at death of HD patients. Dichotomous analysis comparing HD to controls is widely used to study the effects of HTT CAG repeat expansion. However, a potentially more powerful approach is a continuous analysis strategy that takes advantage of all of the different CAG lengths, to capture effects that are expected to be critical to HD pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: We used continuous and dichotomous approaches to analyze microarray gene expression data from 107 human control and HD lymphoblastoid cell lines. Of all probes found to be significant in a continuous analysis by CAG length, only 21.4% were so identified by a dichotomous comparison of HD versus controls. Moreover, of probes significant by dichotomous analysis, only 33.2% were also significant in the continuous analysis. Simulations revealed that the dichotomous approach would require substantially more than 107 samples to either detect 80% of the CAG-length correlated changes revealed by continuous analysis or to reduce the rate of significant differences that are not CAG length-correlated to 20% (n = 133 or n = 206, respectively. Given the superior power of the continuous approach, we calculated the correlation structure between HTT CAG repeat lengths and gene expression levels and created a freely available searchable website, "HD CAGnome," that allows users to examine continuous relationships between HTT CAG and expression levels of ∼20,000 human genes. CONCLUSIONS/SIGNIFICANCE: Our results reveal limitations of dichotomous approaches compared to the power of continuous analysis to study a disease where human genotype-phenotype relationships strongly support a role for a continuum of CAG length-dependent changes. The compendium of HTT CAG length-gene expression level relationships found at the HD CAGnome now provides

  16. Discrepancies in reporting the CAG repeat lengths for Huntington's disease.

    Science.gov (United States)

    Quarrell, Oliver W; Handley, Olivia; O'Donovan, Kirsty; Dumoulin, Christine; Ramos-Arroyo, Maria; Biunno, Ida; Bauer, Peter; Kline, Margaret; Landwehrmeyer, G Bernhard

    2012-01-01

    Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original results from 121 laboratories across 15 countries. We report on 1326 duplicate results; a discrepancy in reporting the upper allele occurred in 51% of cases, this reduced to 13.3% and 9.7% when we applied acceptable measurement errors proposed by the American College of Medical Genetics and the Draft European Best Practice Guidelines, respectively. Duplicate results were available for 1250 lower alleles; discrepancies occurred in 40% of cases. Clinically significant discrepancies occurred in 4.0% of cases with a potential unexplained misdiagnosis rate of 0.3%. There was considerable variation in the discrepancy rate among 10 of the countries participating in this study. Out of 1326 samples, 348 were re-analysed by an accredited diagnostic laboratory, based in Germany, with concordance rates of 93% and 94% for the upper and lower alleles, respectively. This became 100% if the acceptable measurement errors were applied. The central laboratory correctly reported allele sizes for six standard reference samples, blind to the known result. Our study differs from external quality assessment (EQA) schemes in that these are duplicate results obtained from a large sample of patients across the whole diagnostic range. We strongly recommend that laboratories state an error rate for their measurement on the report, participate in EQA schemes and use reference materials regularly to adjust their own internal standards.

  17. Factors influencing the clinical expression of intermediate CAG repeat length mutations of the Huntington's disease gene.

    Science.gov (United States)

    Panegyres, Peter K; Shu, Chen-Chun; Chen, Huei-Yang; Paulsen, Jane S

    2015-02-01

    Our aim is to elucidate the clinical variables associated with the development of manifest HD in patients with intermediate CAG repeat lengths. 2,167 participants were seen throughout 44 research sites in the United States, Canada or Australia over a five-year natural history observational study (2006-2011) (Trial # NCT00313495). The Chi-square test and a generalised linear model were used to examine the differences in demographics and cognitive tests among three groups of CAG repeat length. The mixed model was then used to examine the time effect on cognitive assessments by CAG groups. No patient with CAG repeat length 27-35 developed manifest HD, whereas three patients with 36-39 did. Total motor score, maximal chorea score and maximal dystonia score were significantly different at baseline (p CAG 36-39; those with an associated university degree or higher education were less frequently diagnosed as manifest HD (OR 0.10, 95 % CI 0.02-0.54, p = 0.007). Age, smoking and lower education achievement were found to be significantly associated with higher odds of manifest HD in patients with intermediate CAG repeat length mutations.

  18. FETAL FOOT LENGTH AND HAND LENGTH: RELATIONSHIP WITH CROWN RUMP LENGTH AND GESTATIONAL AGE

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    Garima

    2015-12-01

    Full Text Available BACKGROUND Estimation of gestational age of fetus is of great medicolegal importance. Multiple parameters of the fetal anatomical measurements are in use. However, gestational age assessment may be difficult in fetus with anencephaly, hydrocephalus, short limb dysplasia, post mortem destruction or in mutilated case. Study of literature suggests that fetal foot has a characteristic pattern of normal growth and the fetal foot shows gradual increase in length relative to the length of the embryo and could be used to estimate gestational age. The purpose of the present study is to determine the accuracy in estimating gestational age using fetal foot and hand length by studying its relation with crown rump length in the foetuses of Manipuri origin. AIMS AND OBJECTIVES 1 To study the relationship between fetal crown rump length and fetal hand and foot length, thereby determining the accuracy in estimating gestational age by a cross-sectional study. MATERIALS AND METHODS A total of 100 formalin fixed fetuses of Manipuri origin, obtained from the Department of Obstetrics and Gynaecology, Regional Institute of Medical Sciences, Imphal, were included in the study, carried out in the Department of Anatomy, from February 2015 to July 2015. The parameters studied were crown rump length, foot length and hand length of fetuses. The data was analysed using SPSS software by regression analysis. Graphs were also plotted to determine pattern of growth and their correlation with crown rump length if any. RESULTS A total of 100 fetuses were studied, of which 43 were females and 57 were males. The mean foot length and hand length progressively increased with increase in crown rump length. Measurements were not significantly different in right or left side or among male and female fetuses. A statistically significant linear relationship was seen between foot length and crown rump length of the fetus (r=0.980, p<0.0001 and hand length and crown rump length of the fetus

  19. Correlation of normal-range FMR1 repeat length or genotypes and reproductive parameters.

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    Maslow, Bat-Sheva L; Davis, Stephanie; Engmann, Lawrence; Nulsen, John C; Benadiva, Claudio A

    2016-09-01

    This study aims to ascertain whether the length of normal-ranged CGG repeats on the FMR1 gene correlates with abnormal reproductive parameters. We performed a retrospective, cross-sectional study of all FMR1 carrier screening performed as part of routine care at a large university-based fertility center from January 2011 to March 2014. Correlations were performed between normal-range FMR1 length and baseline serum anti-Müllerian hormone (AMH), cycle day 3 follicle stimulating hormone (FSH), ovarian volumes (OV), antral follicle counts (AFC), and incidence of diminished ovarian reserve (DOR), while controlling for the effect of age. Six hundred three FMR1 screening results were collected. One subject was found to be a pre-mutation carrier and was excluded from the study. Baseline serum AMH, cycle day 3 FSH, OV, and AFC data were collected for the 602 subjects with normal-ranged CGG repeats. No significant difference in median age was noted amongst any of the FMR1 repeat genotypes. No significant correlation or association was found between any allele length or genotype, with any of the reproductive parameters or with incidence of DOR at any age (p > 0.05). However, subjects who were less than 35 years old with low/low genotype were significantly more likely to have below average AMH levels compared to those with normal/normal genotype (RR 3.82; 95 % CI 1.38-10.56). This large study did not demonstrate any substantial association between normal-range FMR1 repeat lengths and reproductive parameters.

  20. Paternal age and telomere length in twins

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob B; Dalgård, Christine; Mangino, Massimo

    2015-01-01

    . Based on two independent (discovery and replication) twin studies, comprising 889 twin pairs, we show an increase in the resemblance of leukocyte telomere length between dizygotic twins of older fathers, which is not seen in monozygotic twins. This phenomenon might result from a paternal age...

  1. Age and disease at an arms length

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    a chronic (previously fatal) disease. The active elderly often stick to their image of themselves as active, youthful and energetic in spite of a chronic disease. Old age and disease is not what they identify with and seems to be conceived at an arms length. In the paper the author explores how health...

  2. The relationship between anogenital distance and the androgen receptor CAG repeat length

    OpenAIRE

    Eisenberg, Michael L.; Hsieh, Tung-Chin; Pastuszak, Alexander W; McIntyre, Matthew G.; Walters, Rustin C; Lamb, Dolores J.; Lipshultz, Larry I

    2013-01-01

    Anogenital distance (AGD) is used to define degree of virilization of genital development, with shorter length being associated with feminization and male infertility. The first exon of the androgen receptor (AR) consists of a polymorphic sequence of cytosine–adenine–guanine (CAG) repeats, with longer CAG repeat lengths being associated with decreased receptor function. We sought to determine if there is an association between AGD and AR CAG repeat length. A cross-sectional, prospective cohor...

  3. The relationship between anogenital distance and the androgen receptor CAG repeat length

    Institute of Scientific and Technical Information of China (English)

    Michael L Eisenberg; Tung-Chin Hsieh; Alexander W Pastuszak; Matthew G McIntyre; Rustin C Walters; Dolores J Lamb; Larry I Lipshultz

    2013-01-01

    Anogenital distance (AGD) is used to define degree of virilization of genital development,with shorter length being associated with feminization and male infertility.The first exon of the androgen receptor (AR) consists of a polymorphic sequence of cytosine-adenine-guanine (CAG) repeats,with longer CAG repeat lengths being associated with decreased receptor function.We sought to determine if there is an association between AGD and AR CAG repeat length.A cross-sectional,prospective cohort of men evaluated at a urology clinic at a single institution was recruited.AGD (the distance from the posterior scrotum to the anal verge) and penile length (PL) were measured.Sanger DNA sequence analysis was used to define CAG repeat length.AGD and CAG repeat lengths in 195 men were determined.On unadjusted analysis,there was no linear relationship between CAG repeat length and PL (P=0.17) or AGD (P=0.31).However,on sub-population analyses,those men with longer CAG repeat lengths (>26) had significantly shorter AGDs compared to men with shorter CAG repeat lengths.For example,the mean AGD was 41.9 vs.32.4 mm with a CAG repeat length ≤ 26 vs.>26 (P=0.01).In addition,when stratifying the cohort based on AGD,those with AGD less than the median (i.e.40 mm) had a longer CAG repeat length compared to men with an AGD >40 mm (P=0.02).In summary,no linear relationship was found between AGD and AR CAG repeat length overall.

  4. The relationship between anogenital distance and the androgen receptor CAG repeat length.

    Science.gov (United States)

    Eisenberg, Michael L; Hsieh, Tung-Chin; Pastuszak, Alexander W; McIntyre, Matthew G; Walters, Rustin C; Lamb, Dolores J; Lipshultz, Larry I

    2013-03-01

    Anogenital distance (AGD) is used to define degree of virilization of genital development, with shorter length being associated with feminization and male infertility. The first exon of the androgen receptor (AR) consists of a polymorphic sequence of cytosine-adenine-guanine (CAG) repeats, with longer CAG repeat lengths being associated with decreased receptor function. We sought to determine if there is an association between AGD and AR CAG repeat length. A cross-sectional, prospective cohort of men evaluated at a urology clinic at a single institution was recruited. AGD (the distance from the posterior scrotum to the anal verge) and penile length (PL) were measured. Sanger DNA sequence analysis was used to define CAG repeat length. AGD and CAG repeat lengths in 195 men were determined. On unadjusted analysis, there was no linear relationship between CAG repeat length and PL (P=0.17) or AGD (P=0.31). However, on sub-population analyses, those men with longer CAG repeat lengths (>26) had significantly shorter AGDs compared to men with shorter CAG repeat lengths. For example, the mean AGD was 41.9 vs. 32.4 mm with a CAG repeat length ≤26 vs. >26 (P=0.01). In addition, when stratifying the cohort based on AGD, those with AGD less than the median (i.e. 40 mm) had a longer CAG repeat length compared to men with an AGD >40 mm (P=0.02). In summary, no linear relationship was found between AGD and AR CAG repeat length overall.

  5. [Telomere length, telomerase activity, stress and aging].

    Science.gov (United States)

    Spivak, I M; Mikhelson, V M; Spivak, D L

    2015-01-01

    The review is dedicated to analysis of data available at present time concerning possible influence of stress upon telomere lengths and telomerase activity, as well as various ways of counteracting it. Present-day telomerase theory of aging gains a new impetus, shedding light upon the influence of psychological state of humans and their ability to counteract stress, upon the process of aging. It also tends to regard telomere shortening and the decrease in the activity of telomerase as a marker of level of the ability to adapt to both inner and outer influences. Both aging and age-dependent diseases are proved to be substantially retarded not only by the administration of drugs, but also by psychological means, which forms a good way towards healthy longevity. With complete understanding of the impossibility to prevent or even to slow down natural senescence itself, these methods allow to remove causes, which accelerate senescence, and to increase the average human longevity.

  6. Effect of CAG repeat length on psychiatric disorders in Huntington's disease.

    Science.gov (United States)

    Vassos, Evangelos; Panas, Marios; Kladi, Athina; Vassilopoulos, Dimitrios

    2008-06-01

    There is strong evidence that the length of CAG repeats, in patients with Huntington's disease (HD), govern the age of onset and the rate of clinical progression of neurological symptoms. However, psychiatric manifestations of the disease have not been examined as comprehensively. Seventy two Greek patients with Huntington's disease had DNA testing and were clinically assessed by means of a semi-structured interview (SCID) and four self-rated questionnaires. Genotype-phenotype correlations were examined. The CAG repeat length had a significant negative association with the age of onset of psychiatric disorders, the total level of functioning and the MMSE. However, the probability of developing a psychiatric disorder and the severity of psychiatric symptoms were not determined by the trinucleotide expansion, after controlling for the duration of illness, sex, and age of the subjects. The factors that determine the development of psychiatric symptoms in HD patients seem not to be limited to a dose related toxicity of the expanded Huntington. It is hypothesized that alternative genetic or environmental factors underlie the pathogenesis of the psychiatric phenotype.

  7. The relationship between CAG repeat length and clinical progression in Huntington's disease.

    Science.gov (United States)

    Ravina, Bernard; Romer, Megan; Constantinescu, Radu; Biglan, Kevin; Brocht, Alicia; Kieburtz, Karl; Shoulson, Ira; McDermott, Michael P

    2008-07-15

    The objective of this study was to examine the relationship between CAG repeat length (CAGn) and clinical progression in patients with Huntington's disease (HD). There are conflicting reports about the relationship between CAGn and clinical progression of HD. We conducted an analysis of data from the Coenzyme Q10 and Remacemide Evaluation in Huntington's Disease (CARE-HD) clinical trial. We modeled progression over 30 months on the Unified Huntington's Disease Rating Scale (UHDRS) and supplemental neuropsychological and behavioral tests using multiple linear regression. Mean subject age was 47.9 +/- 10.5 years and mean CAGn was 45.0 +/- 4.1. Multiple linear regression revealed statistically significant associations between CAGn and worsening on several motor, cognitive, and functional outcomes, but not behavioral outcomes. Many effects were clinically important; 10 additional CAG repeats were associated with an 81% increase in progression on the Independence Scale. These associations were not observed in the absence of age adjustment. Age at the time of assessment confounds the association between CAGn and progression. Adjusting for age shows that longer CAGn is associated with greater clinical progression of HD. This finding may account for the variable results from previous studies examining CAGn and progression. Adjusting for CAGn may be important for clinical trials.

  8. Reduced CAG repeats length in androgen receptor gene is associated with violent criminal behavior.

    Science.gov (United States)

    Rajender, Singh; Pandu, Guguluth; Sharma, J D; Gandhi, K P C; Singh, Lalji; Thangaraj, Kumarasamy

    2008-09-01

    Androgens mediate their functions through androgen receptors (AR). The two triplet repeats in the AR gene (CAG and GGN) are highly polymorphic among various populations and have been extensively studied in diverse clinical conditions and antisocial personality disorders. Several studies have reported either higher levels of testosterone among rapists or the correlation of shorter CAG repeats with criminal activities. However, to date, no study has analyzed AR gene in rapists worldwide, and no study has been conducted on criminals from Indian subcontinent. Therefore, we have analyzed the AR-CAG repeat length in 645 men, of which 241 were convicted for rape, 107 for murder, 26 for both murder and rape, and 271 were control males. The aim was to explore if there was any correlation between CAG repeat length and criminal behavior. The study revealed significantly shorter CAG repeats in the rapists (mean 18.44 repeats) and murderers (mean 17.59 repeats) compared to the control men (mean 21.19 repeats). The criminals who committed murder after rape had a far shorter mean repeat length (mean 17.31 repeats) in comparison to the controls or those convicted of rape or murder alone. In short, our study suggests that the reduced CAG repeats in the AR gene are associated with criminal behavior. This, along with other studies, would help in understanding the biological factors associated with the antisocial or criminal activities.

  9. CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

    DEFF Research Database (Denmark)

    Lee, J-M; Ramos, E M; Lee, J-H;

    2012-01-01

    Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound...... implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs....

  10. Relationships among androgen receptor CAG repeat polymorphism, sex hormones and penile length in Han adult men from China: a cross-sectional study

    OpenAIRE

    Yan-Min Ma; Kai-Jie Wu; Liang Ning; Jin Zeng; Bo Kou; Hong-Jun Xie; Zhen-Kun Ma; Xin-Yang Wang; Yong-Guang Gong; Da-Lin He

    2014-01-01

    This study aimed to investigate the correlations among androgen receptor (AR) CAG repeat polymorphism, sex hormones and penile length in healthy Chinese young adult men. Two hundred and fifty-three healthy men (aged 22.8 ± 3.1 years) were enrolled. The individuals were grouped as CAG short (CAG S ) if they harbored repeat length of ≤20 or as CAG long (CAG L ) if their CAG repeat length was >20. Body height/weight, penile length and other parameters were examined and recorded by the specified ...

  11. Relationships among androgen receptor CAG repeat polymorphism, sex hormones and penile length in Han adult men from China: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Yan-Min Ma

    2014-06-01

    Full Text Available This study aimed to investigate the correlations among androgen receptor (AR CAG repeat polymorphism, sex hormones and penile length in healthy Chinese young adult men. Two hundred and fifty-three healthy men (aged 22.8 ± 3.1 years were enrolled. The individuals were grouped as CAG short (CAG S if they harbored repeat length of ≤20 or as CAG long (CAG L if their CAG repeat length was >20. Body height/weight, penile length and other parameters were examined and recorded by the specified physicians; CAG repeat polymorphism was determined by the polymerase chain reaction (PCR method; and the serum levels of the sex hormones were detected by radioimmunoassay. Student's t-test or linear regression analysis was used to assess the associations among AR CAG repeat polymorphism, sex hormones and penile length. This investigation showed that the serum total testosterone (T level was positively associated with the AR CAG repeat length (P = 0.01; whereas, no significant correlation of T or AR CAG repeat polymorphism with the penile length was found (P = 0.593. Interestingly, an inverse association was observed between serum prolactin (PRL levels and penile length by linear regression analyses (β= −0.024, P = 0.039, 95% confidence interval (CI: −0.047, 0. Collectively, this study provides the first evidence that serum PRL, but not T or AR CAG repeat polymorphism, is correlated with penile length in the Han adult population from northwestern China.

  12. Relationships among androgen receptor CAG repeat polymorphism, sex hormones and penile length in Han adult men from China: a cross-sectional study.

    Science.gov (United States)

    Ma, Yan-Min; Wu, Kai-Jie; Ning, Liang; Zeng, Jin; Kou, Bo; Xie, Hong-Jun; Ma, Zhen-Kun; Wang, Xin-Yang; Gong, Yong-Guang; He, Da-Lin

    2014-01-01

    This study aimed to investigate the correlations among androgen receptor (AR) CAG repeat polymorphism, sex hormones and penile length in healthy Chinese young adult men. Two hundred and fifty-three healthy men (aged 22.8 ± 3.1 years) were enrolled. The individuals were grouped as CAG short (CAG S ) if they harbored repeat length of ≤ 20 or as CAG long (CAG L ) if their CAG repeat length was >20. Body height/weight, penile length and other parameters were examined and recorded by the specified physicians; CAG repeat polymorphism was determined by the polymerase chain reaction (PCR) method; and the serum levels of the sex hormones were detected by radioimmunoassay. Student's t-test or linear regression analysis was used to assess the associations among AR CAG repeat polymorphism, sex hormones and penile length. This investigation showed that the serum total testosterone (T) level was positively associated with the AR CAG repeat length (P = 0.01); whereas, no significant correlation of T or AR CAG repeat polymorphism with the penile length was found (P = 0.593). Interestingly, an inverse association was observed between serum prolactin (PRL) levels and penile length by linear regression analyses (β= -0.024, P = 0.039, 95% confidence interval (CI): -0.047, 0). Collectively, this study provides the first evidence that serum PRL, but not T or AR CAG repeat polymorphism, is correlated with penile length in the Han adult population from northwestern China.

  13. Relationships among androgen receptor CAG repeat polymorphism, sex hormones and penile length in Han adult men from China:a cross-sectional study

    Institute of Scientific and Technical Information of China (English)

    YanMin Ma; DaLin He; KaiJie Wu; Liang Ning; Jin Zeng; Bo Kou; HongJun Xie; ZhenKun Ma; XinYang Wang; YongGuang Gong

    2014-01-01

    This study aimed to investigate the correlations among androgen receptor (AR) CAG repeat polymorphism, sex hormones and penile length in healthy Chinese young adult men. Two hundred and iffty-three healthy men (aged 22.8 ± 3.1 years) were enrolled. The individuals were grouped as CAG short (CAGS) if they harbored repeat length of≤20 or as CAG long (CAGL) if their CAG repeat length was>20. Body height/weight, penile length and other parameters were examined and recorded by the speciifed physicians;CAG repeat polymorphism was determined by the polymerase chain reaction (PCR) method;and the serum levels of the sex hormones were detected by radioimmunoassay. Student’s t-test or linear regression analysis was used to assess the associations among AR CAG repeat polymorphism, sex hormones and penile length. This investigation showed that the serum total testosterone (T) level was positively associated with the AR CAG repeat length (P= 0.01); whereas, no signiifcant correlation of T or AR CAG repeat polymorphism with the penile length was found (P= 0.593). Interestingly, an inverse association was observed between serum prolactin (PRL) levels and penile length by linear regression analyses (b=-0.024, P= 0.039, 95%conifdence interval (CI):-0.047, 0). Collectively, this study provides the ifrst evidence that serum PRL, but not T or AR CAG repeat polymorphism, is correlated with penile length in the Han adult population from northwestern China.

  14. Critical nucleus size for disease-related polyglutamine aggregation is repeat length dependent

    OpenAIRE

    Kar, Karunakar; Jayaraman, Murali; Sahoo, Bankanidhi; Kodali, Ravindra; Wetzel, Ronald

    2011-01-01

    Since polyglutamine (polyQ) aggregate formation has been implicated as playing an important role in expanded CAG repeat diseases, it is important to understand the biophysics underlying the initiation of aggregation. Previously we showed that relatively long polyQ peptides aggregate by nucleated growth polymerization and a monomeric critical nucleus. We show here that, over a short repeat length range from Q26 to Q23, the size of the critical nucleus for aggregation increases from monomeric t...

  15. A critical window of CAG repeat-length correlates with phenotype severity in the R6/2 mouse model of Huntington's disease.

    Science.gov (United States)

    Cummings, Damian M; Alaghband, Yasaman; Hickey, Miriam A; Joshi, Prasad R; Hong, S Candice; Zhu, Chunni; Ando, Timothy K; André, Véronique M; Cepeda, Carlos; Watson, Joseph B; Levine, Michael S

    2012-01-01

    The R6/2 mouse is the most frequently used model for experimental and preclinical drug trials in Huntington's disease (HD). When the R6/2 mouse was first developed, it carried exon 1 of the huntingtin gene with ~150 cytosine-adenine-guanine (CAG) repeats. The model presented with a rapid and aggressive phenotype that shared many features with the human condition and was particularly similar to juvenile HD. However, instability in the CAG repeat length due to different breeding practices has led to both decreases and increases in average CAG repeat lengths among colonies. Given the inverse relationship in human HD between CAG repeat length and age at onset and to a degree, the direct relationship with severity of disease, we have investigated the effect of altered CAG repeat length. Four lines, carrying ~110, ~160, ~210, and ~310 CAG repeats, were examined using a battery of tests designed to assess the basic R6/2 phenotype. These included electrophysiological properties of striatal medium-sized spiny neurons, motor activity, inclusion formation, and protein expression. The results showed an unpredicted, inverted "U-shaped" relationship between CAG repeat length and phenotype; increasing the CAG repeat length from 110 to 160 exacerbated the R6/2 phenotype, whereas further increases to 210 and 310 CAG repeats greatly ameliorated the phenotype. These findings demonstrate that the expected relationship between CAG repeat length and disease severity observed in humans is lost in the R6/2 mouse model and highlight the importance of CAG repeat-length determination in preclinical drug trials that use this model.

  16. Triplet repeat mutation length gains correlate with cell-type specific vulnerability in Huntington disease brain.

    Science.gov (United States)

    Shelbourne, Peggy F; Keller-McGandy, Christine; Bi, Wenya Linda; Yoon, Song-Ro; Dubeau, Louis; Veitch, Nicola J; Vonsattel, Jean Paul; Wexler, Nancy S; Arnheim, Norman; Augood, Sarah J

    2007-05-15

    Huntington disease is caused by the expansion of a CAG repeat encoding an extended glutamine tract in a protein called huntingtin. Here, we provide evidence supporting the hypothesis that somatic increases of mutation length play a role in the progressive nature and cell-selective aspects of HD pathogenesis. Results from micro-dissected tissue and individual laser-dissected cells obtained from human HD cases and knock-in HD mice indicate that the CAG repeat is unstable in all cell types tested although neurons tend to have longer mutation length gains than glia. Mutation length gains occur early in the disease process and continue to accumulate as the disease progresses. In keeping with observed patterns of cell loss, neuronal mutation length gains tend to be more prominent in the striatum than in the cortex of low-grade human HD cases, less so in more advanced cases. Interestingly, neuronal sub-populations of HD mice appear to have different propensities for mutation length gains; in particular, smaller mutation length gains occur in nitric oxide synthase-positive striatal interneurons (a relatively spared cell type in HD) compared with the pan-striatal neuronal population. More generally, the data demonstrate that neuronal changes in HD repeat length can be at least as great, if not greater, than those observed in the germline. The fact that significant CAG repeat length gains occur in non-replicating cells also argues that processes such as inappropriate mismatch repair rather than DNA replication are involved in generating mutation instability in HD brain tissue.

  17. Accurate aging of juvenile salmonids using fork lengths

    Science.gov (United States)

    Sethi, Suresh; Gerken, Jonathon; Ashline, Joshua

    2017-01-01

    Juvenile salmon life history strategies, survival, and habitat interactions may vary by age cohort. However, aging individual juvenile fish using scale reading is time consuming and can be error prone. Fork length data are routinely measured while sampling juvenile salmonids. We explore the performance of aging juvenile fish based solely on fork length data, using finite Gaussian mixture models to describe multimodal size distributions and estimate optimal age-discriminating length thresholds. Fork length-based ages are compared against a validation set of juvenile coho salmon, Oncorynchus kisutch, aged by scales. Results for juvenile coho salmon indicate greater than 95% accuracy can be achieved by aging fish using length thresholds estimated from mixture models. Highest accuracy is achieved when aged fish are compared to length thresholds generated from samples from the same drainage, time of year, and habitat type (lentic versus lotic), although relatively high aging accuracy can still be achieved when thresholds are extrapolated to fish from populations in different years or drainages. Fork length-based aging thresholds are applicable for taxa for which multiple age cohorts coexist sympatrically. Where applicable, the method of aging individual fish is relatively quick to implement and can avoid ager interpretation bias common in scale-based aging.

  18. Electrostatic effect of H1-histone protein binding on nucleosome repeat length

    Science.gov (United States)

    Cherstvy, Andrey G.; Teif, Vladimir B.

    2014-08-01

    Within a simple biophysical model we describe the effect of electrostatic binding of H1 histone proteins on the nucleosome repeat length in chromatin. The length of wrapped DNA optimizes its binding energy to the histone core and the elastic energy penalty of DNA wrapping. The magnitude of the effect predicted from our model is in agreement with the systematic experimental data on the linear variation of nucleosome repeat lengths with H1/nucleosome ratio (Woodcock C L et al 2006 Chromos. Res. 14 17-25). We compare our model to the data for different cell types and organisms, with a widely varying ratio of bound H1 histones per nucleosome. We underline the importance of this non-specific histone-DNA charge-balance mechanism in regulating the positioning of nucleosomes and the degree of compaction of chromatin fibers in eukaryotic cells.

  19. Variation in CAG and GGN repeat lengths and CAG/GGN haplotype in androgen receptor gene polymorphism and prostate carcinoma in Nigerians.

    Science.gov (United States)

    Akinloye, O; Gromoll, J; Simoni, M

    2011-01-01

    Prostate cancer has become the most common cancer in Nigerian men. The growth of the prostate gland depends on circulating androgens and intracellular steroid signalling pathways. The effects of androgens are mediated through the androgen receptor (AR), a nuclear transcription factor encoded by the AR gene. The common polymorphisms, CAG and GGN repeats, in exon 1 of this gene have been implicated as possible risk factors. Thus far, existing supporting data are scanty and none are from sub-Saharan African populations. Therefore, this study investigates the possible association between AR polymorphism repeat length (CAG and GGN) and prostate cancer in Nigerians. A total of 261 subjects (70 with prostate cancer, 68 with benign prostate hyperplasia [BPH], 123 age-matched apparently normal subjects as controls) were studied. CAG and GGN repeats length were determined by fragment length analysis using GeneScan. The CAG repeat length in prostate cancer and in BPH compared to the controls was significantly different (P CAG repeats showing a significant odds ratio (OR) in both cases. However, this was not observed in GGN repeat length, which showed no significant difference between cases and controls (P > 0.05). CAG and GGN haplotype variation showed no significant difference between cases and controls (P > 0.05), except that the haplotypes CAG > or =21 and GGN CAG repeat length is a risk factor for prostate cancer, and also suggests an association with BPH.

  20. Read length and repeat resolution: Exploring prokaryote genomes using next-generation sequencing technologies

    KAUST Repository

    Cahill, Matt J.

    2010-07-12

    Background: There are a growing number of next-generation sequencing technologies. At present, the most cost-effective options also produce the shortest reads. However, even for prokaryotes, there is uncertainty concerning the utility of these technologies for the de novo assembly of complete genomes. This reflects an expectation that short reads will be unable to resolve small, but presumably abundant, repeats. Methodology/Principal Findings: Using a simple model of repeat assembly, we develop and test a technique that, for any read length, can estimate the occurrence of unresolvable repeats in a genome, and thus predict the number of gaps that would need to be closed to produce a complete sequence. We apply this technique to 818 prokaryote genome sequences. This provides a quantitative assessment of the relative performance of various lengths. Notably, unpaired reads of only 150nt can reconstruct approximately 50% of the analysed genomes with fewer than 96 repeat-induced gaps. Nonetheless, there is considerable variation amongst prokaryotes. Some genomes can be assembled to near contiguity using very short reads while others require much longer reads. Conclusions: Given the diversity of prokaryote genomes, a sequencing strategy should be tailored to the organism under study. Our results will provide researchers with a practical resource to guide the selection of the appropriate read length. 2010 Cahill et al.

  1. Read length and repeat resolution: exploring prokaryote genomes using next-generation sequencing technologies.

    Directory of Open Access Journals (Sweden)

    Matt J Cahill

    Full Text Available BACKGROUND: There are a growing number of next-generation sequencing technologies. At present, the most cost-effective options also produce the shortest reads. However, even for prokaryotes, there is uncertainty concerning the utility of these technologies for the de novo assembly of complete genomes. This reflects an expectation that short reads will be unable to resolve small, but presumably abundant, repeats. METHODOLOGY/PRINCIPAL FINDINGS: Using a simple model of repeat assembly, we develop and test a technique that, for any read length, can estimate the occurrence of unresolvable repeats in a genome, and thus predict the number of gaps that would need to be closed to produce a complete sequence. We apply this technique to 818 prokaryote genome sequences. This provides a quantitative assessment of the relative performance of various lengths. Notably, unpaired reads of only 150nt can reconstruct approximately 50% of the analysed genomes with fewer than 96 repeat-induced gaps. Nonetheless, there is considerable variation amongst prokaryotes. Some genomes can be assembled to near contiguity using very short reads while others require much longer reads. CONCLUSIONS: Given the diversity of prokaryote genomes, a sequencing strategy should be tailored to the organism under study. Our results will provide researchers with a practical resource to guide the selection of the appropriate read length.

  2. CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

    Science.gov (United States)

    Lee, J.-M.; Ramos, E.M.; Lee, J.-H.; Gillis, T.; Mysore, J.S.; Hayden, M.R.; Warby, S.C.; Morrison, P.; Nance, M.; Ross, C.A.; Margolis, R.L.; Squitieri, F.; Orobello, S.; Di Donato, S.; Gomez-Tortosa, E.; Ayuso, C.; Suchowersky, O.; Trent, R.J.A.; McCusker, E.; Novelletto, A.; Frontali, M.; Jones, R.; Ashizawa, T.; Frank, S.; Saint-Hilaire, M.H.; Hersch, S.M.; Rosas, H.D.; Lucente, D.; Harrison, M.B.; Zanko, A.; Abramson, R.K.; Marder, K.; Sequeiros, J.; Paulsen, J.S.; Landwehrmeyer, G.B.; Myers, R.H.; MacDonald, M.E.; Durr, Alexandra; Rosenblatt, Adam; Frati, Luigi; Perlman, Susan; Conneally, Patrick M.; Klimek, Mary Lou; Diggin, Melissa; Hadzi, Tiffany; Duckett, Ayana; Ahmed, Anwar; Allen, Paul; Ames, David; Anderson, Christine; Anderson, Karla; Anderson, Karen; Andrews, Thomasin; Ashburner, John; Axelson, Eric; Aylward, Elizabeth; Barker, Roger A.; Barth, Katrin; Barton, Stacey; Baynes, Kathleen; Bea, Alexandra; Beall, Erik; Beg, Mirza Faisal; Beglinger, Leigh J.; Biglan, Kevin; Bjork, Kristine; Blanchard, Steve; Bockholt, Jeremy; Bommu, Sudharshan Reddy; Brossman, Bradley; Burrows, Maggie; Calhoun, Vince; Carlozzi, Noelle; Chesire, Amy; Chiu, Edmond; Chua, Phyllis; Connell, R.J.; Connor, Carmela; Corey-Bloom, Jody; Craufurd, David; Cross, Stephen; Cysique, Lucette; Santos, Rachelle Dar; Davis, Jennifer; Decolongon, Joji; DiPietro, Anna; Doucette, Nicholas; Downing, Nancy; Dudler, Ann; Dunn, Steve; Ecker, Daniel; Epping, Eric A.; Erickson, Diane; Erwin, Cheryl; Evans, Ken; Factor, Stewart A.; Farias, Sarah; Fatas, Marta; Fiedorowicz, Jess; Fullam, Ruth; Furtado, Sarah; Garde, Monica Bascunana; Gehl, Carissa; Geschwind, Michael D.; Goh, Anita; Gooblar, Jon; Goodman, Anna; Griffith, Jane; Groves, Mark; Guttman, Mark; Hamilton, Joanne; Harrington, Deborah; Harris, Greg; Heaton, Robert K.; Helmer, Karl; Henneberry, Machelle; Hershey, Tamara; Herwig, Kelly; Howard, Elizabeth; Hunter, Christine; Jankovic, Joseph; Johnson, Hans; Johnson, Arik; Jones, Kathy; Juhl, Andrew; Kim, Eun Young; Kimble, Mycah; King, Pamela; Klimek, Mary Lou; Klöppel, Stefan; Koenig, Katherine; Komiti, Angela; Kumar, Rajeev; Langbehn, Douglas; Leavitt, Blair; Leserman, Anne; Lim, Kelvin; Lipe, Hillary; Lowe, Mark; Magnotta, Vincent A.; Mallonee, William M.; Mans, Nicole; Marietta, Jacquie; Marshall, Frederick; Martin, Wayne; Mason, Sarah; Matheson, Kirsty; Matson, Wayne; Mazzoni, Pietro; McDowell, William; Miedzybrodzka, Zosia; Miller, Michael; Mills, James; Miracle, Dawn; Montross, Kelsey; Moore, David; Mori, Sasumu; Moser, David J.; Moskowitz, Carol; Newman, Emily; Nopoulos, Peg; Novak, Marianne; O'Rourke, Justin; Oakes, David; Ondo, William; Orth, Michael; Panegyres, Peter; Pease, Karen; Perlman, Susan; Perlmutter, Joel; Peterson, Asa; Phillips, Michael; Pierson, Ron; Potkin, Steve; Preston, Joy; Quaid, Kimberly; Radtke, Dawn; Rae, Daniela; Rao, Stephen; Raymond, Lynn; Reading, Sarah; Ready, Rebecca; Reece, Christine; Reilmann, Ralf; Reynolds, Norm; Richardson, Kylie; Rickards, Hugh; Ro, Eunyoe; Robinson, Robert; Rodnitzky, Robert; Rogers, Ben; Rosenblatt, Adam; Rosser, Elisabeth; Rosser, Anne; Price, Kathy; Price, Kathy; Ryan, Pat; Salmon, David; Samii, Ali; Schumacher, Jamy; Schumacher, Jessica; Sendon, Jose Luis Lópenz; Shear, Paula; Sheinberg, Alanna; Shpritz, Barnett; Siedlecki, Karen; Simpson, Sheila A.; Singer, Adam; Smith, Jim; Smith, Megan; Smith, Glenn; Snyder, Pete; Song, Allen; Sran, Satwinder; Stephan, Klaas; Stober, Janice; Sü?muth, Sigurd; Suter, Greg; Tabrizi, Sarah; Tempkin, Terry; Testa, Claudia; Thompson, Sean; Thomsen, Teri; Thumma, Kelli; Toga, Arthur; Trautmann, Sonja; Tremont, Geoff; Turner, Jessica; Uc, Ergun; Vaccarino, Anthony; van Duijn, Eric; Van Walsem, Marleen; Vik, Stacie; Vonsattel, Jean Paul; Vuletich, Elizabeth; Warner, Tom; Wasserman, Paula; Wassink, Thomas; Waterman, Elijah; Weaver, Kurt; Weir, David; Welsh, Claire; Werling-Witkoske, Chris; Wesson, Melissa; Westervelt, Holly; Weydt, Patrick; Wheelock, Vicki; Williams, Kent; Williams, Janet; Wodarski, Mary; Wojcieszek, Joanne; Wood, Jessica; Wood-Siverio, Cathy; Wu, Shuhua; Yastrubetskaya, Olga; de Yebenes, Justo Garcia; Zhao, Yong Qiang; Zimbelman, Janice; Zschiegner, Roland; Aaserud, Olaf; Abbruzzese, Giovanni; Andrews, Thomasin; Andrich, Jurgin; Antczak, Jakub; Arran, Natalie; Artiga, Maria J. Saiz; Bachoud-Lévi, Anne-Catherine; Banaszkiewicz, Krysztof; di Poggio, Monica Bandettini; Bandmann, Oliver; Barbera, Miguel A.; Barker, Roger A.; Barrero, Francisco; Barth, Katrin; Bas, Jordi; Beister, Antoine; Bentivoglio, Anna Rita; Bertini, Elisabetta; Biunno, Ida; Bjørgo, Kathrine; Bjørnevoll, Inga

    2012-01-01

    Objective: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. Methods: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. Results: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. Conclusions: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors. Neurology® 2012;78:690–695 PMID:22323755

  3. CAG repeat length in androgen receptor gene is not associated with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Bruson, A; Sambataro, F; Querin, G; D'Ascenzo, C; Palmieri, A; Agostini, J; Gaiani, A; Angelini, C; Galbiati, M; Poletti, A; Pennuto, M; Pegoraro, E; Clementi, M; Soraru, G

    2012-10-01

    Epidemiological and clinical studies show higher prevalence of amyotrophic lateral sclerosis (ALS) in males than in females and more severe lesions in androgen receptor (AR)-expressing tissues. The AR gene contains a polymorphic CAG trinucleotide repeat, whose expansion over a certain threshold is toxic to motor neurons, causing spinal and bulbar muscular atrophy (SBMA). We tested the hypothesis that the AR CAG repeat linked to SBMA is a risk factor for ALS. We analyzed AR CAG expansions in 336 patients with ALS and 100 controls. We found a negative association of AR CAG expansions with ALS susceptibility, clinical presentation, and survival. Our findings do not support a role of the AR CAG repeat length in ALS. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

  4. Critical nucleus size for disease-related polyglutamine aggregation is repeat length dependent

    Science.gov (United States)

    Kar, Karunakar; Jayaraman, Murali; Sahoo, Bankanidhi; Kodali, Ravindra; Wetzel, Ronald

    2010-01-01

    Since polyglutamine (polyQ) aggregate formation has been implicated as playing an important role in expanded CAG repeat diseases, it is important to understand the biophysics underlying the initiation of aggregation. Previously we showed that relatively long polyQ peptides aggregate by nucleated growth polymerization and a monomeric critical nucleus. We show here that, over a short repeat length range from Q26 to Q23, the size of the critical nucleus for aggregation increases from monomeric to dimeric to tetrameric. This variation in nucleus size suggests a common duplex anti-parallel β-sheet framework for the nucleus, and further supports the feasibility of an organized monomeric aggregation nucleus for longer polyQ repeat peptides. The data also suggest that a change in aggregation nucleus size may play a role in the pathogenicity of polyQ expansion in this series of familial neurodegenerative diseases. PMID:21317897

  5. Genetic Association Between Androgen Receptor Gene CAG Repeat Length Polymorphism and Male Infertility: A Meta-Analysis.

    Science.gov (United States)

    Pan, Bihui; Li, Rui; Chen, Yao; Tang, Qiuqin; Wu, Wei; Chen, Liping; Lu, Chuncheng; Pan, Feng; Ding, Hongjuan; Xia, Yankai; Hu, Lingqing; Chen, Daozhen; Sha, Jiahao; Wang, Xinru

    2016-03-01

    The association between polymorphism of androgen receptor gene CAG (AR-CAG) and male infertility in several studies was controversial. Based on studies on association between AR-CAG repeat length and male infertility in recent years, an updated meta-analysis is needed. We aimed to evaluate the association between AR-CAG repeat length and male infertility in advantage of the data in all published reports.We searched for reports published before August 2015 using PubMed, CNKI, VIP, and WanFang. Data on sample size, mean, and standard deviation (SD) of AR-CAG repeat length were extracted independently by 3 investigators.Forty-four reports were selected based on criteria. The overall infertile patients and azoospermic patients were found to have longer AR-CAG repeat length (standard mean difference (SMD) = 0.19, 95% confidence interval (CI): 0.10-0.28, P CAG repeat length was longer in infertile men in Asian, Caucasian, and mixed races (SMD = 0.25, 95% CI: 0.08-0.43, P CAG repeat length was associated with male infertility. The subgroup study on races shows that increased AR-CAG repeat length was associated with male infertility in Asian, Caucasian, and mixed races. Increased AR-CAG repeat length was also associated with azoospermia.This meta-analysis supports that increased androgen receptor CAG length is capable of causing male infertility susceptibility.

  6. RUNX2 tandem repeats and the evolution of facial length in placental mammals

    Directory of Open Access Journals (Sweden)

    Pointer Marie A

    2012-06-01

    Full Text Available Abstract Background When simple sequence repeats are integrated into functional genes, they can potentially act as evolutionary ‘tuning knobs’, supplying abundant genetic variation with minimal risk of pleiotropic deleterious effects. The genetic basis of variation in facial shape and length represents a possible example of this phenomenon. Runt-related transcription factor 2 (RUNX2, which is involved in osteoblast differentiation, contains a functionally-important tandem repeat of glutamine and alanine amino acids. The ratio of glutamines to alanines (the QA ratio in this protein seemingly influences the regulation of bone development. Notably, in domestic breeds of dog, and in carnivorans in general, the ratio of glutamines to alanines is strongly correlated with facial length. Results In this study we examine whether this correlation holds true across placental mammals, particularly those mammals for which facial length is highly variable and related to adaptive behavior and lifestyle (e.g., primates, afrotherians, xenarthrans. We obtained relative facial length measurements and RUNX2 sequences for 41 mammalian species representing 12 orders. Using both a phylogenetic generalized least squares model and a recently-developed Bayesian comparative method, we tested for a correlation between genetic and morphometric data while controlling for phylogeny, evolutionary rates, and divergence times. Non-carnivoran taxa generally had substantially lower glutamine-alanine ratios than carnivorans (primates and xenarthrans with means of 1.34 and 1.25, respectively, compared to a mean of 3.1 for carnivorans, and we found no correlation between RUNX2 sequence and face length across placental mammals. Conclusions Results of our diverse comparative phylogenetic analyses indicate that QA ratio does not consistently correlate with face length across the 41 mammalian taxa considered. Thus, although RUNX2 might function as a ‘tuning knob’ modifying face

  7. RUNX2 tandem repeats and the evolution of facial length in placental mammals.

    Science.gov (United States)

    Pointer, Marie A; Kamilar, Jason M; Warmuth, Vera; Chester, Stephen G B; Delsuc, Frédéric; Mundy, Nicholas I; Asher, Robert J; Bradley, Brenda J

    2012-06-28

    When simple sequence repeats are integrated into functional genes, they can potentially act as evolutionary 'tuning knobs', supplying abundant genetic variation with minimal risk of pleiotropic deleterious effects. The genetic basis of variation in facial shape and length represents a possible example of this phenomenon. Runt-related transcription factor 2 (RUNX2), which is involved in osteoblast differentiation, contains a functionally-important tandem repeat of glutamine and alanine amino acids. The ratio of glutamines to alanines (the QA ratio) in this protein seemingly influences the regulation of bone development. Notably, in domestic breeds of dog, and in carnivorans in general, the ratio of glutamines to alanines is strongly correlated with facial length. In this study we examine whether this correlation holds true across placental mammals, particularly those mammals for which facial length is highly variable and related to adaptive behavior and lifestyle (e.g., primates, afrotherians, xenarthrans). We obtained relative facial length measurements and RUNX2 sequences for 41 mammalian species representing 12 orders. Using both a phylogenetic generalized least squares model and a recently-developed Bayesian comparative method, we tested for a correlation between genetic and morphometric data while controlling for phylogeny, evolutionary rates, and divergence times. Non-carnivoran taxa generally had substantially lower glutamine-alanine ratios than carnivorans (primates and xenarthrans with means of 1.34 and 1.25, respectively, compared to a mean of 3.1 for carnivorans), and we found no correlation between RUNX2 sequence and face length across placental mammals. Results of our diverse comparative phylogenetic analyses indicate that QA ratio does not consistently correlate with face length across the 41 mammalian taxa considered. Thus, although RUNX2 might function as a 'tuning knob' modifying face length in carnivorans, this relationship is not conserved across

  8. Somatic expansion of the Huntington's disease CAG repeat in the brain is associated with an earlier age of disease onset.

    Science.gov (United States)

    Swami, Meera; Hendricks, Audrey E; Gillis, Tammy; Massood, Tiffany; Mysore, Jayalakshmi; Myers, Richard H; Wheeler, Vanessa C

    2009-08-15

    The age of onset of Huntington's disease (HD) is determined primarily by the length of the HD CAG repeat mutation, but is also influenced by other modifying factors. Delineating these modifiers is a critical step towards developing validated therapeutic targets in HD patients. The HD CAG repeat is somatically unstable, undergoing progressive length increases over time, particularly in brain regions that are the targets of neurodegeneration. Here, we have explored the hypothesis that somatic instability of the HD CAG repeat is itself a modifier of disease. Using small-pool PCR, we quantified somatic instability in the cortex region of the brain from a cohort of HD individuals exhibiting phenotypic extremes of young and old disease onset as predicted by the length of their constitutive HD CAG repeat lengths. After accounting for constitutive repeat length, somatic instability was found to be a significant predictor of onset age, with larger repeat length gains associated with earlier disease onset. These data are consistent with the hypothesis that somatic HD CAG repeat length expansions in target tissues contribute to the HD pathogenic process, and support pursuing factors that modify somatic instability as viable therapeutic targets.

  9. Impact of CAG repeat length in the androgen receptor gene on male infertility - a meta-analysis.

    Science.gov (United States)

    Xiao, Feifan; Lan, Aihua; Lin, Zhidi; Song, Jianfei; Zhang, Yuening; Li, Jiatong; Gu, Kailong; Lv, Baihao; Zhao, Dong; Zeng, Siping; Zhang, Ruoheng; Zhao, Wei; Pan, Zhengyan; Deng, Xiaozhen; Yang, Xiaoli

    2016-07-01

    CAG repeats are polymorphic nucleotide repeats present in the androgen receptor gene. Many studies have estimated the association between CAG repeat length and male infertility, but the conclusions are controversial. Previous meta-analyses have come to different conclusions; however, new studies have been published. An updated meta-analysis was conducted. PubMed, CBM, CNKI and Web of Science databases were systematically searched for studies published from 1 January 2000 to 1 October 2015. Case-control studies on the association between CAG repeat length and male infertility using appropriate methodology were included. Forty studies were selected, including 3858 cases and 3161 controls. Results showed statistically significantly longer CAG repeat length among cases compared with controls (SMD = 0.14; 95% CI, 0.02-0.26). Shorter repeat length was associated with a lower risk of male infertility compared with a longer repeat length in the overall analysis (OR = 0.79, 95% CI: 0.66-0.95). Moreover, CAG repeat length was associated with male infertility in Caucasian populations, but not Asian or Egyptian populations. Subgroup analysis revealed no significant difference in German populations, but CAG repeat length was associated with male infertility in China and the USA. There were no significant differences between cases and controls in azoospermia and severe oligozoospermia.

  10. Telomere length is longer in women with late maternal age

    DEFF Research Database (Denmark)

    Fagan, Erin; Sun, Fangui; Bae, Harold

    2017-01-01

    OBJECTIVE:: Maternal age at birth of last child has been associated with maternal longevity. The aim of this study was to determine whether older women with a history of late maternal age at last childbirth had a longer leukocyte telomere length than those with maternal age at last childbirth of ...

  11. CAG repeat length does not associate with the rate of cerebellar degeneration in spinocerebellar ataxia type 3

    OpenAIRE

    Huang, Shang-Ran; Wu, Yu-Te; Jao, Chii-Wen; Soong, Bing-wen; Lirng, Jiing-Feng; Wu, Hsiu-Mei; Wang, Po-Shan

    2016-01-01

    This cross-sectional study investigated the correlation between the CAG repeat length and the degeneration of cerebellum in spinocerebellar ataxia type 3 (SCA3) patients based on neuroimaging approaches. Forty SCA3 patients were recruited and classified into two subgroups according to their CAG repeat lengths (≥ 74 and

  12. Androgen Receptor CAG Repeat Length Is Associated With Body Fat and Serum SHBG in Boys

    DEFF Research Database (Denmark)

    Mouritsen, Annette; Hagen, Casper P; Sørensen, Kaspar

    2013-01-01

    ) had lower levels of SHBG (88 vs 125 nmol/L) (P skinfold thickness (41 vs 31 mm) (P = .06) compared with boys with an average number of CAG repeats (CAG 21-23). In contrast, the inverse association was observed at puberty (at 12 years of age...

  13. Effect of stride length manipulation on symptoms of exercise-induced muscle damage and the repeated bout effect.

    Science.gov (United States)

    Rowlands, A V; Eston, R G; Tilzey, C

    2001-05-01

    This study assessed the effects of stride length on symptoms of exercise-induced muscle damage after downhill running and whether the extent of the symptoms sustained in a repeated bout of downhill running are influenced by stride length manipulation in the first bout. Eighteen males aged 21.1 +/- 0.6 years (mean +/- s) were allocated to one of three groups for bout one: preferred stride frequency, overstride and understride. Bout two was performed 2 weeks later at the participants' preferred stride frequency. Maximal isometric force and perceived muscle soreness were assessed pre-test and 30 min, 24, 48 and 72 h post-exercise for each downhill run. Three-factor analyses of variance with repeated measures on time and bout were used for analysis. Results revealed a three-way interaction for soreness (F8,60 = 3.56, P stride frequency groups perceived less soreness than the preferred stride frequency group in bout one. Strength retention was greater after bout two for all groups. In conclusion, strength retention after a repeated bout appears to be independent of the damage experienced in the initial bout of downhill running. However, understriding may provide least protection against soreness in a subsequent bout.

  14. Polymorphic CAG and GGC repeat lengths in the androgen receptor gene and prostate cancer risk: analysis of a Brazilian population.

    Science.gov (United States)

    Silva Neto, Brasil; Koff, Walter J; Biolchi, Vanderlei; Brenner, Cleber; Biolo, Karlo D; Spritzer, Poli Mara; Brum, Ilma S

    2008-02-01

    Variations in transcriptional activity of the androgen receptor (AR) are related to polymorphic CAG and GGC repeats in exon 1 of the AR gene. We investigated the association between CAG and GGC repeat length and the risk of prostate cancer in a case-control study from a Brazilian population. We evaluated 49 patients and 51 healthy controls. DNA was extracted from peripheral leukocytes and the AR gene was analyzed by fragment analysis (GeneMapper software, Applied Biosystems, Foster City, California, USA). CAG and GGC mean lengths were not different between cases and controls. The risk for prostate cancer was higher for CAG repeats repeat lengths (CAG + GGC) repeats ( 17) were not associated with risk for prostate cancer (OR = 1.13 [95% CI 0.47-2.75]). In conclusion, fewer number of CAG repeats and total repeats (CAG + GGC) in the AR gene may be associated with increased risk for prostate cancer.

  15. Correlation of CAG repeat length between the maternal and paternal allele of the Huntingtin gene: evidence for assortative mating

    Directory of Open Access Journals (Sweden)

    Wassink Tom

    2011-10-01

    Full Text Available Abstract Triplet repeats contribute to normal variation in behavioral traits and when expanded, cause brain disorders. While Huntington's Disease is known to be caused by a CAG triplet repeat in the gene Huntingtin, the effect of CAG repeats on brain function below disease threshold has not been studied. The current study shows a significant correlation between the CAG repeat length of the maternal and paternal allele in the Huntingtin gene among healthy subjects, suggesting assortative mating.

  16. (TG/CAn repeats in human gene families: abundance and selective patterns of distribution according to function and gene length

    Directory of Open Access Journals (Sweden)

    Ramachandran Srinivasan

    2005-06-01

    Full Text Available Abstract Background Creation of human gene families was facilitated significantly by gene duplication and diversification. The (TG/CAn repeats exhibit length variability, display genome-wide distribution, and are abundant in the human genome. Accumulation of evidences for their multiple functional roles including regulation of transcription and stimulation of recombination and splicing elect them as functional elements. Here, we report analysis of the distribution of (TG/CAn repeats in human gene families. Results The 1,317 human gene families were classified into six functional classes. Distribution of (TG/CAn repeats were analyzed both from a global perspective and from a stratified perspective based on their biological properties. The number of genes with repeats decreased with increasing repeat length and several genes (53% had repeats of multiple types in various combinations. Repeats were positively associated with the class of Signaling and communication whereas, they were negatively associated with the classes of Immune and related functions and of Information. The proportion of genes with (TG/CAn repeats in each class was proportional to the corresponding average gene length. The repeat distribution pattern in large gene families generally mirrored the global distribution pattern but differed particularly for Collagen gene family, which was rich in repeats. The position and flanking sequences of the repeats of Collagen genes showed high conservation in the Chimpanzee genome. However the majority of these repeats displayed length polymorphism. Conclusion Positive association of repeats with genes of Signaling and communication points to their role in modulation of transcription. Negative association of repeats in genes of Information relates to the smaller gene length, higher expression and fundamental role in cellular physiology. In genes of Immune and related functions negative association of repeats perhaps relates to the smaller gene

  17. Repeatability of OCT lens thickness measures with age and accommodation.

    Science.gov (United States)

    Doyle, Lesley; Little, Julie-Anne; Saunders, Kathryn J

    2013-12-01

    To investigate crystalline lens thickness (LT) across a range of ages and accommodative demands and to evaluate the repeatability of LT measurements using the Visante Anterior Segment Optical Coherence Tomographer (AS-OCT) (Zeiss Meditec, Germany) under non-cycloplegic conditions. Participants were 98 visually normal adults aged 18-75 years, stratified into age groups of 18-29, 30-39, 40-49, 50-59, and 60-75 years of age. Images of the crystalline lens were taken using the Visante AS-OCT during stimulation of accommodation at demands of 0, 1, 2, 3, 4, 5, and 8 D with accommodative response measured in a subgroup of participants. Images were analyzed and LT measured assuming a refractive index of 1.42. Repeat measures were taken from 86 participants for each accommodative demand at a second visit. The mean unaccommodated LT for all participants was 4.07 ± 0.40 mm. An average increase in LT of 20 μm per year was calculated (linear regression, R² = 0.61, F(1,89) = 143.92, p report the repeatability of LT measures using the Visante AS-OCT in the non-cyclopleged eye. It has also demonstrated the ability of the Visante AS-OCT to detect small changes in lens thickness with accommodation.

  18. Androgen receptor CAG repeats length polymorphism and the risk of polycystic ovarian syndrome (PCOS.

    Directory of Open Access Journals (Sweden)

    Singh Rajender

    Full Text Available OBJECTIVE: Polycystic ovarian syndrome (PCOS refers to an inheritable androgen excess disorder characterized by multiple small follicles located at the ovarian periphery. Hyperandrogenism in PCOS, and inverse correlation between androgen receptor (AR CAG numbers and AR function, led us to hypothesize that CAG length variations may affect PCOS risk. METHODS: CAG repeat region of 169 patients recruited following strictly defined Rotterdam (2003 inclusion criteria and that of 175 ethnically similar control samples, were analyzed. We also conducted a meta-analysis on the data taken from published studies, to generate a pooled estimate on 2194 cases and 2242 controls. RESULTS: CAG bi-allelic mean length was between 8.5 and 24.5 (mean = 17.43, SD = 2.43 repeats in the controls and between 11 and 24 (mean = 17.39, SD = 2.29 repeats in the cases, without any significant difference between the two groups. Further, comparison of bi-allelic mean and its frequency distribution in three categories (short, moderate and long alleles did not show any significant difference between controls and various case subgroups. Frequency distribution of bi-allelic mean in two categories (extreme and moderate alleles showed over-representation of extreme sized alleles in the cases with marginally significant value (50.3% vs. 61.5%, χ(2 = 4.41; P = 0.036, which turned insignificant upon applying Bonferroni correction for multiple comparisons. X-chromosome inactivation analysis showed no significant difference in the inactivation pattern of CAG alleles or in the comparison of weighed bi-allelic mean between cases and controls. Meta-analysis also showed no significant correlation between CAG length and PCOS risk, except a minor over-representation of short CAG alleles in the cases. CONCLUSION: CAG bi-allelic mean length did not differ between controls and cases/case sub-groups nor did the allele distribution. Over-representation of short

  19. Analysis of the androgen receptor CAG repeats length in Iranian patients with idiopathic non-obstructive azoospermia

    Directory of Open Access Journals (Sweden)

    Sohreh Zare-Karizi

    2016-03-01

    Conclusion: Although our results indicate a significant negative correlation between the length of CAG repeat and male infertility, however, other genetic modifiers may be required in order to cause male infertility.

  20. CAG repeat length does not associate with the rate of cerebellar degeneration in spinocerebellar ataxia type 3

    Directory of Open Access Journals (Sweden)

    Shang-Ran Huang

    2017-01-01

    Full Text Available This cross-sectional study investigated the correlation between the CAG repeat length and the degeneration of cerebellum in spinocerebellar ataxia type 3 (SCA3 patients based on neuroimaging approaches. Forty SCA3 patients were recruited and classified into two subgroups according to their CAG repeat lengths (≥74 and <74. We measured each patient's Scale for the Assessment and Rating of Ataxia (SARA score, N-acetylaspartate (NAA/creatine (Cr ratios based on magnetic resonance spectroscopy (MRS, and 3-dimensional fractal dimension (3D-FD values derived from magnetic resonance imaging (MRI results. Furthermore, the 3D-FD values were used to construct structural covariance networks based on graph theoretical analysis. The results revealed that SCA3 patients with a longer CAG repeat length demonstrated earlier disease onset. However, the CAG repeat length did not significantly correlate with their SARA scores, cerebellar NAA/Cr ratios or cerebellar 3D-FD values. Network dissociation between cerebellar regions and parietal-occipital regions was found in SCA3 patients with CAG ≥ 74, but not in those with CAG < 74. In conclusion, the CAG repeat length is uncorrelated with the change of SARA score, cerebellar function and cerebellar structure in SCA3. Nevertheless, a longer CAG repeat length may indicate early structural covariance network dissociation.

  1. Variability and repeatability in gestation length related to litter performance in female pigs on commercial farms.

    Science.gov (United States)

    Sasaki, Y; Koketsu, Y

    2007-07-15

    Forecasting gestation length (GL) in sows enables producers to be prepared to provide assistance at farrowing, or for timely treatment to induce parturition. The objectives of the present study were to determine GL across parities, the repeatability and correlation of the GL, and associations of GL with the three litter size variables (total pigs born, pigs born alive, and dead piglets) and longevity. This study was conducted on 94 farms and encompassed 66,254 farrowing records of 13,715 sows born during 1999. Variance components and correlation analyses were used to determine the repeatability and the correlations of GL. Mixed-effects models were used to analyze associations of GL with litter size variables and longevity. The mean of GL across parities was from 115.2 to 115.4 d. The proportions of GL 114, 115, and 116 d for all farrowing events were 19.2, 30.8, and 22.2%, respectively. The GL between parities were correlated (0.40/=117 d (P<0.01). Sows with GL

  2. Body mass index is inversely correlated with the expanded CAG repeat length in SCA3/MJD patients.

    Science.gov (United States)

    Saute, Jonas Alex Morales; Silva, Andrew Chaves Feitosa da; Souza, Gabriele Nunes; Russo, Aline Dutra; Donis, Karina Carvalho; Vedolin, Leonardo; Saraiva-Pereira, Maria Luiza; Portela, Luis Valmor Cruz; Jardim, Laura Bannach

    2012-09-01

    Spinocerebellar ataxia type 3, also known as Machado-Joseph disease (SCA3/MJD), is an autosomal dominant neurodegenerative disorder with no current treatment. We aimed to evaluate the body mass index (BMI) of patients with SCA3/MJD and to assess the correlations with clinical, molecular, biochemical, and neuroimaging findings. A case-control study with 46 SCA3/MJD patients and 42 healthy, non-related control individuals with similar age and sex was performed. Clinical evaluation was done with the ataxia scales SARA and NESSCA. Serum insulin, insulin-like growth factor 1 (IGF-1) and magnetic resonance imaging normalized volumetries of cerebellum and brain stem were also assessed. BMI was lower in SCA3/MJD patients when compared to controls (p = 0.01). BMI was associated with NESSCA, expanded CAG repeat number (CAG)n, age of onset, age, disease duration, and serum insulin levels; however, in the linear regression model, (CAG)n was the only variable independently associated with BMI, in an inverse manner (R = -0.396, p = 0.015). In this report, we present evidence that low BMI is not only present in SCA3/MJD, but is also directly related to the length of the expanded CAG repeats, which is the causative mutation of the disease. This association points that weight loss might be a primary disturbance of SCA3/MJD, although further detailed analyses are necessary for a better understanding of the nutritional deficit and its role in the pathophysiology of SCA3/MJD.

  3. Leukocyte telomere length: Effects of schizophrenia, age, and gender.

    Science.gov (United States)

    Wolkowitz, Owen M; Jeste, Dilip V; Martin, Averria Sirkin; Lin, Jue; Daly, Rebecca E; Reuter, Chase; Kraemer, Helena

    2017-02-01

    Schizophrenia is linked with early medical comorbidity and mortality. These observations indicate possible "accelerated biological aging" in schizophrenia, although prior findings are mixed, and few such studies have examined the role of gender. One putative marker of biological aging is leukocyte telomere length (LTL), which typically shortens with age. We assessed LTL in phenotypically well characterized 134 individuals with schizophrenia (60 women and 74 men) and 123 healthy comparison subjects (HCs) (66 women and 57 men), aged 26 to 65 years. Overall, LTL was inversely associated with age (t(249) = -6.2, p schizophrenia and HC groups (t(249) = 2.48, p = 0.014), with women having longer LTL than men, and a significant gender X diagnosis effect (t(249) = 2.43, p = 0.016) - at the average sample age, women with schizophrenia had shorter LTL than HC women. Gender, not the diagnosis of schizophrenia, was the major factor involved with LTL shortening across the age range studied. We discuss the constraints of a cross-sectional design and other methodological issues, and indicate future directions. Understanding the impact of schizophrenia on biological aging will require separate evaluations in men and women. Published by Elsevier Ltd.

  4. Recombination frequency in plasmid DNA containing direct repeats--predictive correlation with repeat and intervening sequence length.

    Science.gov (United States)

    Oliveira, Pedro H; Lemos, Francisco; Monteiro, Gabriel A; Prazeres, Duarte M F

    2008-09-01

    In this study, a simple non-linear mathematical function is proposed to accurately predict recombination frequencies in bacterial plasmid DNA harbouring directly repeated sequences. The mathematical function, which was developed on the basis of published data on deletion-formation in multicopy plasmids containing direct-repeats (14-856 bp) and intervening sequences (0-3872 bp), also accounts for the strain genotype in terms of its recA function. A bootstrap resampling technique was used to estimate confidence intervals for the correlation parameters. More than 92% of the predicted values were found to be within a pre-established +/-5-fold interval of deviation from experimental data. The correlation does not only provide a way to predict, with good accuracy, the recombination frequency, but also opens the way to improve insight into these processes.

  5. Shorter CAG repeat length in the AR gene is associated with poor outcome in head and neck cancer

    DEFF Research Database (Denmark)

    Rosa, Fabíola Encinas; dos Santos, Rodrigo Mattos; Poli-Frederico, Regina Célia

    2007-01-01

    of the AR [CAG](n) repeat length. Sixty-nine individuals without cancer were used as a control group for both procedures. The Log-rank test was used to compare overall survival and disease-free survival curves. The Cox proportional hazards regression models were performed to determine the [CAG](n) repeats...... as an independent prognostic factor. RESULTS: Patients with alleles survival (P=0.0325) and with recurrence or metastasis (RR 2.52, CI 95%). In the female group, the allele 2 (longer allele) showed a significant lower mean of [CAG](n) repeat when...... compared to the control group. Microsatellite instability was detected in nine cases in both procedures. In six out of these nine cases, we observed a reduction of the AR [CAG](n) repeat length. LOH was detected in one out of 17 women informative for oral cancer in both procedures. CONCLUSION...

  6. Genetic screening in infertile Mexican men: chromosomal abnormalities, Y chromosome deletions, and androgen receptor CAG repeat length.

    Science.gov (United States)

    Martínez-Garza, Sandra Guadalupe; Gallegos-Rivas, Mayra Celina; Vargas-Maciel, Marcos; Rubio-Rubio, Juan Manuel; de Los Monteros-Rodríguez, Mario Espinosa; González-Ortega, Claudia; Cancino-Villarreal, Patricia; de Lara, Luis G Vazquez; Gutiérrez-Gutiérrez, Antonio Martín

    2008-01-01

    In our study, we analyzed chromosomal abnormalities, Y chromosome deletions, androgen receptor CAG repeat length and their association with defective spermatogenesis in infertile Mexican men. Eighty-two infertile patients and 40 controls were screened for karyotypic abnormalities, Y chromosome microdeletions, and CAG repeats. Nine infertile males (11%) carried chromosomal abnormalities and 10 (12.2%) presented Y chromosome microdeletions. The mean CAG repeat length was 21.6 and 20.88 base pairs in idiopathic infertile males and controls, respectively. Our results suggest that chromosomal aberrations and Y-chromosomal microdeletions are related to male infertility in Mexican men. In addition, expansion of the CAG repeat segments of the androgen receptor is not correlated with male idiopathic infertility.

  7. Genetic Association Between Androgen Receptor Gene CAG Repeat Length Polymorphism and Male Infertility: A Meta-Analysis

    OpenAIRE

    Pan, Bihui; Li, Rui; CHEN, YAO; Tang, Qiuqin; Wu, Wei; Chen, Liping; Lu, Chuncheng; Pan, Feng; Hongjuan DING; Xia,Yankai; Hu, Lingqing; Chen, Daozhen; Sha, Jiahao; Wang, Xinru

    2016-01-01

    Abstract The association between polymorphism of androgen receptor gene CAG (AR-CAG) and male infertility in several studies was controversial. Based on studies on association between AR-CAG repeat length and male infertility in recent years, an updated meta-analysis is needed. We aimed to evaluate the association between AR-CAG repeat length and male infertility in advantage of the data in all published reports. We searched for reports published before August 2015 using PubMed, CNKI, VIP, an...

  8. Repeat length variation in the dopamine D4 receptor gene shows no evidence of association with schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Daniels, J.; Williams, J.; Asherson, P. [Univ. of Wales College of Medicine, Cardiff (United Kingdom)] [and others

    1994-09-15

    The D4 receptor has been shown to exist in several allelic forms reflecting variation in the number of 48 base-pair sequence repeats in the putative cytoplasmic loop. We report a comparison of repeat length variation between schizophrenic patients and controls. Our sample of 106 unrelated schizophrenic cases and 119 controls showed no significant differences in allele or genotype distribution between patients and controls. In particular, we were unable to support the previous observation of an excess of 4-repeat homozygotes in patients. 16 refs., 2 tabs.

  9. Effects of CAG repeat length, HTT protein length and protein context on cerebral metabolism measured using magnetic resonance spectroscopy in transgenic mouse models of Huntington's disease.

    Science.gov (United States)

    Jenkins, Bruce G; Andreassen, Ole A; Dedeoglu, Alpaslan; Leavitt, Blair; Hayden, Michael; Borchelt, David; Ross, Christopher A; Ferrante, Robert J; Beal, M Flint

    2005-10-01

    Huntington's disease is a neurodegenerative illness caused by expansion of CAG repeats at the N-terminal end of the protein huntingtin. We examined longitudinal changes in brain metabolite levels using in vivo magnetic resonance spectroscopy in five different mouse models. There was a large (>50%) exponential decrease in N-acetyl aspartate (NAA) with time in both striatum and cortex in mice with 150 CAG repeats (R6/2 strain). There was a linear decrease restricted to striatum in N171-82Q mice with 82 CAG repeats. Both the exponential and linear decreases of NAA were paralleled in time by decreases in neuronal area measured histologically. Yeast artificial chromosome transgenic mice with 72 CAG repeats, but low expression levels, had less striatal NAA loss than the N171-82Q mice (15% vs. 43%). We evaluated the effect of gene context in mice with an approximate 146 CAG repeat on the hypoxanthine phosphoribosyltransferase gene (HPRT). HPRT mice developed an obese phenotype in contrast to weight loss in the R6/2 and N171-82Q mice. These mice showed a small striatal NAA loss (21%), and a possible increase in brain lipids detectable by magnetic resonance (MR) spectroscopy and decreased brain water T1. Our results indicate profound metabolic defects that are strongly affected by CAG repeat length, as well as gene expression levels and protein context.

  10. Quantification of age-dependent somatic CAG repeat instability in Hdh CAG knock-in mice reveals different expansion dynamics in striatum and liver.

    Directory of Open Access Journals (Sweden)

    Jong-Min Lee

    Full Text Available BACKGROUND: Age at onset of Huntington's disease (HD is largely determined by the CAG trinucleotide repeat length in the HTT gene. Importantly, the CAG repeat undergoes tissue-specific somatic instability, prevalent in brain regions that are disease targets, suggesting a potential role for somatic CAG repeat instability in modifying HD pathogenesis. Thus, understanding underlying mechanisms of somatic CAG repeat instability may lead to discoveries of novel therapeutics for HD. Investigation of the dynamics of the CAG repeat size changes over time may provide insights into the mechanisms underlying CAG repeat instability. METHODOLOGY/PRINCIPAL FINDINGS: To understand how the HTT CAG repeat length changes over time, we quantified somatic instability of the CAG repeat in Huntington's disease CAG knock-in mice from 2-16 months of age in liver, striatum, spleen and tail. The HTT CAG repeat in spleen and tail was very stable, but that in liver and striatum expanded over time at an average rate of one CAG per month. Interestingly, the patterns of repeat instability were different between liver and striatum. Unstable CAG repeats in liver repeatedly gained similar sizes of additional CAG repeats (approximately two CAGs per month, maintaining a distinct population of unstable repeats. In contrast, unstable CAG repeats in striatum gained additional repeats with different sizes resulting in broadly distributed unstable CAG repeats. Expanded CAG repeats in the liver were highly enriched in polyploid hepatocytes, suggesting that the pattern of liver instability may reflect the restriction of the unstable repeats to a unique cell type. CONCLUSIONS/SIGNIFICANCE: Our results are consistent with repeat expansion occurring as a consequence of recurrent small repeat insertions that differ in different tissues. Investigation of the specific mechanisms that underlie liver and striatal instability will contribute to our understanding of the relationship between

  11. Aerobic capacity in wild satin bowerbirds: repeatability and effects of age, sex and condition.

    Science.gov (United States)

    Chappell, Mark A; Savard, Jean-Francois; Siani, Jennifer; Coleman, Seth W; Keagy, Jason; Borgia, Gerald

    2011-10-01

    Individual variation in aerobic capacity has been extensively studied, especially with respect to condition, maturity or pathogen infection, and to gain insights into mechanistic foundations of performance. However, its relationship to mate competition is less well understood, particularly for animals in natural habitats. We examined aerobic capacity [maximum rate of O2 consumption (VO2,max) in forced exercise] in wild satin bowerbirds, an Australian passerine with a non-resource based mating system and strong intermale sexual competition. We tested for repeatability of mass and VO2,max, differences among age and sex classes, and effects of several condition indices. In adult males, we examined interactions between aerobic performance and bower ownership (required for male mating success). There was significant repeatability of mass and VO2,max within and between years, but between-year repeatability was lower than within-year repeatability. VO2,max varied with an overall scaling to mass(0.791), but most variance in VO2,max was not explained by mass. Indicators of condition (tarsus and wing length asymmetry, the ratio of tarsus length to mass) were not correlated to VO2,max. Ectoparasite counts were weakly correlated to VO2,max across all age-sex classes but not within any class. Adult males, the cohort with the most intense levels of mating competition, had higher VO2,max than juvenile birds or adult females. However, there was no difference between the VO2,max of bower-owning males and that of males not known to hold bowers. Thus one major factor determining male reproductive success was not correlated to aerobic performance.

  12. Intermediate CAG repeat lengths (53,54) for MJD/SCA3 are associated with an abnormal phenotype

    NARCIS (Netherlands)

    van Alfen, N; Sinke, R J; Zwarts, M J; Gabreëls-Festen, A; Praamstra, P; Kremer, B P; Horstink, M W

    2001-01-01

    We report on a Dutch family in which 4 members in 2 generations have intermediate repeat lengths (53 and 54) for Machado-Joseph Disease/Spinocerebellar Ataxia (MJD/SCA3). All but the youngest have a restless legs syndrome with fasciculations and a sensorimotor axonal polyneuropathy. Central neurolog

  13. Intermediate CAG repeat lengths (53,54) for MJD/SCA3 are associated with an abnormal phenotype.

    NARCIS (Netherlands)

    Alfen, N. van; Sinke, R.J.; Zwarts, M.J.; Gabreëls-Festen, A.A.W.M.; Praamstra, P.; Kremer, H.P.H.; Horstink, M.W.I.M.

    2001-01-01

    We report on a Dutch family in which 4 members in 2 generations have intermediate repeat lengths (53 and 54) for Machado-Joseph Disease/Spinocerebellar Ataxia (MJD/SCA3). All but the youngest have a restless legs syndrome with fasciculations and a sensorimotor axonal polyneuropathy. Central neurolog

  14. Intermediate CAG repeat lengths (53,54) for MJD/SCA3 are associated with an abnormal phenotype

    NARCIS (Netherlands)

    van Alfen, N; Sinke, R J; Zwarts, M J; Gabreëls-Festen, A; Praamstra, P; Kremer, B P; Horstink, M W

    2001-01-01

    We report on a Dutch family in which 4 members in 2 generations have intermediate repeat lengths (53 and 54) for Machado-Joseph Disease/Spinocerebellar Ataxia (MJD/SCA3). All but the youngest have a restless legs syndrome with fasciculations and a sensorimotor axonal polyneuropathy. Central neurolog

  15. Androgen receptor CAG repeat length and TMPRSS2:ETS prostate cancer risk: results From the Prostate Cancer Prevention Trial.

    Science.gov (United States)

    Figg, William D; Chau, Cindy H; Price, Douglas K; Till, Cathee; Goodman, Phyllis J; Cho, Yonggon; Varella-Garcia, Marileila; Reichardt, Juergen K V; Tangen, Catherine M; Leach, Robin J; van Bokhoven, Adrie; Thompson, Ian M; Lucia, M Scott

    2014-07-01

    To investigate the association between the length of the polymorphic trinucleotide CAG microsatellite repeats in exon 1 of the AR gene and the risk of prostate cancer containing TMPRSS2:ETS fusion genes. This nested case-control study came from subjects enrolled in the Prostate Cancer Prevention Trial and included 195 biopsy-proven prostate cancer cases with a known TMPRSS2:ETS status and 1344 matched controls. There was no association between the CAG repeat length and the risk of TMPRSS2:ETS-positive (odds ratio, 0.97; 95% confidence interval, 0.91-1.04) or TMPRSS2:ETS-negative prostate cancer (odds ratio, 1.04; 95% confidence interval, 0.97-1.11) and in patients with low- or high-grade disease. Our findings suggested that AR CAG repeats are not associated with TMPRSS2:ETS formation in prostate cancer. Published by Elsevier Inc.

  16. Non-linear association between androgen receptor CAG repeat length and risk of male subfertility--a meta-analysis.

    Science.gov (United States)

    Nenonen, H A; Giwercman, A; Hallengren, E; Giwercman, Y L

    2011-08-01

    The CAG repeat in the androgen receptor (AR) has been widely studied in association with male infertility, but the results are conflicting. In a recent meta-analysis, infertile men had repeat longer CAG stretch than fertile men when analysed in a linear regression model assuming that AR function diminishes with increasing CAG length. However, in vitro, a non-linear activity pattern was recently demonstrated so that ARs containing short and long stretches, respectively, displayed lower activity than the AR of median length. These results prompted us to explore the possible association between CAG number and male infertility risk in a stratified manner on the basis of data from the mentioned meta-analysis and subjects from our clinical unit. The study population included 3915 men, 1831 fertile and 2084 infertile. Data were divided into three categories: CAGCAG 22-23 (reference) and CAG>23 and analysed in a binary logistic regression model. Men with CAGCAG>23 had 20% increased odds ratio of infertility compared with carriers of the median lengths [for CAGCAG>23: p=0.02, 95% CI: 1.03-1.44]. These results show that an alternative model to a linear one for the genotype-phenotype association in relation to AR CAG repeats is likely, as lengths close to the median confine lowest risk of infertility.

  17. TAA repeat variation in the GRIK2 gene does not influence age at onset in Huntington's disease

    Science.gov (United States)

    Lee, Ji-Hyun; Lee, Jong-Min; Ramos, Eliana Marisa; Gillis, Tammy; Mysore, Jayalakshmi S.; Kishikawa, Shotaro; Hadzi, Tiffany; Hendricks, Audrey E.; Hayden, Michael R.; Morrison, Patrick J.; Nance, Martha; Ross, Christopher A.; Margolis, Russell L.; Squitieri, Ferdinando; Gellera, Cinzia; Gomez-Tortosa, Estrella; Ayuso, Carmen; Suchowersky, Oksana; Trent, Ronald J.; McCusker, Elizabeth; Novelletto, Andrea; Frontali, Marina; Jones, Randi; Ashizawa, Tetsuo; Frank, Samuel; Saint-Hilaire, Marie-Helene; Hersch, Steven M.; Rosas, Herminia D.; Lucente, Diane; Harrison, Madaline B.; Zanko, Andrea; Abramson, Ruth K.; Marder, Karen; Sequeiros, Jorge; Landwehrmeyer, G. Bernhard; Network, Ira Shoulson; Myers, Richard H.; MacDonald, Marcy E.; Gusella, James F.

    2013-01-01

    Huntington's disease is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat whose length is the major determinant of age at onset but remaining variation appears to be due in part to the effect of genetic modifiers. GRIK2, which encodes GluR6, a mediator of excitatory neurotransmission in the brain, has been suggested in several studies to be a modifier gene based upon a 3′ untranslated region TAA trinucleotide repeat polymorphism. Prior to investing in detailed studies of the functional impact of this polymorphism, we sought to confirm its effect on age at onset in a much larger dataset than in previous investigations. We genotyped the HD CAG repeat and the GRIK2 TAA repeat in DNA samples from 2,911 Huntington's disease subjects with known age at onset, and tested for a potential modifier effect of GRIK2 using a variety of statistical approaches. Unlike previous reports, we detected no evidence of an influence of the GRIK2 TAA repeat polymorphism on age at motor onset. Similarly, the GRIK2 polymorphism did not show significant modifier effect on psychiatric and cognitive age at onset in HD. Comprehensive analytical methods applied to a much larger sample than in previous studies do not support a role for GRIK2 as a genetic modifier of age at onset of clinical symptoms in Huntington's disease. PMID:22771793

  18. Androgen receptor gene CAG repeat length as modifier of the association between Persistent Organohalogen Pollutant exposure markers and semen characteristics

    DEFF Research Database (Denmark)

    Giwercman, Aleksander; Rylander, Lars; Rignell-Hydbom, Anna;

    2007-01-01

    OBJECTIVES: Exposure to persistent organohalogen pollutants was suggested to impair male reproductive function. A gene-environment interaction has been proposed. No genes modifying the effect of persistent organohalogen pollutants on reproductive organs have yet been identified. We aimed...... and morphology) and DNA fragmentation index (DFI) were determined. CAG and GGN repeat lengths were determined by direct sequencing of leukocyte DNA. RESULTS: A statistically significant interaction was found between the CB-153 group and CAG repeat category in relation to sperm concentration and total sperm count...

  19. Dominant effects of the Huntington's disease HTT CAG repeat length are captured in gene-expression data sets by a continuous analysis mathematical modeling strategy.

    Science.gov (United States)

    Lee, Jong-Min; Galkina, Ekaterina I; Levantovsky, Rachel M; Fossale, Elisa; Anne Anderson, Mary; Gillis, Tammy; Srinidhi Mysore, Jayalakshmi; Coser, Kathryn R; Shioda, Toshi; Zhang, Bin; Furia, Matthew D; Derry, Jonathan; Kohane, Isaac S; Seong, Ihn Sik; Wheeler, Vanessa C; Gusella, James F; MacDonald, Marcy E

    2013-08-15

    In Huntington's disease (HD), the size of the expanded HTT CAG repeat mutation is the primary driver of the processes that determine age at onset of motor symptoms. However, correlation of cellular biochemical parameters also extends across the normal repeat range, supporting the view that the CAG repeat represents a functional polymorphism with dominant effects determined by the longer allele. A central challenge to defining the functional consequences of this single polymorphism is the difficulty of distinguishing its subtle effects from the multitude of other sources of biological variation. We demonstrate that an analytical approach based upon continuous correlation with CAG size was able to capture the modest (∼21%) contribution of the repeat to the variation in genome-wide gene expression in 107 lymphoblastoid cell lines, with alleles ranging from 15 to 92 CAGs. Furthermore, a mathematical model from an iterative strategy yielded predicted CAG repeat lengths that were significantly positively correlated with true CAG allele size and negatively correlated with age at onset of motor symptoms. Genes negatively correlated with repeat size were also enriched in a set of genes whose expression were CAG-correlated in human HD cerebellum. These findings both reveal the relatively small, but detectable impact of variation in the CAG allele in global data in these peripheral cells and provide a strategy for building multi-dimensional data-driven models of the biological network that drives the HD disease process by continuous analysis across allelic panels of neuronal cells vulnerable to the dominant effects of the HTT CAG repeat.

  20. Repeated modification of early limb morphogenesis programmes underlies the convergence of relative limb length in Anolis lizards.

    Science.gov (United States)

    Sanger, Thomas J; Revell, Liam J; Gibson-Brown, Jeremy J; Losos, Jonathan B

    2012-02-22

    The independent evolution of similar morphologies has long been a subject of considerable interest to biologists. Does phenotypic convergence reflect the primacy of natural selection, or does development set the course of evolution by channelling variation in certain directions? Here, we examine the ontogenetic origins of relative limb length variation among Anolis lizard habitat specialists to address whether convergent phenotypes have arisen through convergent developmental trajectories. Despite the numerous developmental processes that could potentially contribute to variation in adult limb length, our analyses reveal that, in Anolis lizards, such variation is repeatedly the result of changes occurring very early in development, prior to formation of the cartilaginous long bone anlagen.

  1. Minimum length of direct repeat sequences required for efficient homologous recombination induced by zinc finger nuclease in yeast.

    Science.gov (United States)

    Ren, ChongHua; Yan, Qiang; Zhang, ZhiYing

    2014-10-01

    Zinc finger nuclease (ZFN) technology is a powerful molecular tool for targeted genome modifications and genetic engineering. However, screening for specific ZFs and validation of ZFN activity are labor intensive and time consuming. We previously designed a yeast-based ZFN screening and validation system by inserting a ZFN binding site flanked by a 164 bp direct repeat sequence into the middle of a Gal4 transcription factor, disrupting the open reading frame of the yeast Gal4 gene. Expression of the ZFN causes a double stranded break at its binding site, which promotes the cellular DNA repair system to restore expression of a functional Gal transcriptional factor via homologous recombination. Expression of Gal4 transcription factor leads to activation of three reporter genes in an AH109 yeast two-hybrid strain. However, the 164 bp direct repeat appears to generate spontaneous homologous recombination frequently, resulting in many false positive ZFNs. To overcome this, a series of DNA fragments of various lengths from 10 to 150 bp with 10 bp increase each and 164 bp direct repeats flanking the ZFN binding site were designed and constructed. The results demonstrated that the minimum length required for ZFN-induced homologous recombination was 30 bp, which almost eliminated spontaneous recombination. Using the 30 bp direct repeat sequence, ZFN could efficiently induce homologous recombination, while false positive ZFNs resulting from spontaneous homologous recombination were minimized. Thus, this study provided a simple, fast and sensitive ZFN screening and activity validation system in yeast.

  2. Assessment of Correlation between Androgen Receptor CAG Repeat Length and Infertility in Infertile Men Living in Khuzestan, Iran

    Directory of Open Access Journals (Sweden)

    Saeid Reza Khatami

    2015-02-01

    Full Text Available Background: The androgen receptor (AR gene contains a polymorphic trinucleotide repeat that encodes a polyglutamine tract in its N-terminal transactivation domain (NTAD. We aimed to find a correlation between the length of this polymorphic tract and azoospermia or oligozoospermia in infertile men living in Khuzestan, Iran. Materials and Methods: In this case-control study during two years till 2010, we searched for microdeletions in the Y chromosome in 84 infertile male patients with normal karyotype who lived in Khuzestan Province, Southwest of Iran. All cases (n=12 of azoospermia or oligozoospermia resulting from Y chromosome microdeletions were excluded from our study. The number of CAG repeats in exon 1 of the AR gene was determined in 72 patients with azoospermia or oligozoospermia and in 72 fertile controls, using the polymerase chain reaction (PCR and polyacrylamide gel electrophoresis. Results: Microdeletions were detected in 14.3% (n=12 patients suffering severe oligozoospermia. The mean CAG repeat length was 18.99 ± 0.35 (range, 11-26 and 19.96 ± 0.54 (range, 12-25 in infertile males and controls, respectively. Also in the infertile group, the most common allele was 19 (26.38%, while in controls, it was 25 (22.22%. Conclusion: Y chromosome microdeletions could be one of the main reasons of male infertility living in Khuzestan Province, while there was no correlation between CAG length in AR gene with azoospermia or oligozoospermia in infertile men living in Khuzestan, Iran.

  3. Effects of age and step length on joint kinetics during stepping task.

    Science.gov (United States)

    Bieryla, Kathleen A; Buffinton, Christine

    2015-07-16

    Following a balance perturbation, a stepping response is commonly used to regain support, and the distance of the recovery step can vary. To date, no other studies have examined joint kinetics in young and old adults during increasing step distances, when participants are required to bring their rear foot forward. Therefore, the purpose of this study was to examine age-related differences in joint kinetics with increasing step distance. Twenty young and 20 old adults completed the study. Participants completed a step starting from double support, at an initial distance equal to the individual's average step length. The distance was increased by 10% body height until an unsuccessful attempt. A one-way, repeated measures ANOVA was used to determine the effects of age on joint kinetics during the maximum step distance. A two-way, repeated measures, mixed model ANOVA was used to determine the effects of age, step distance, and their interaction on joint kinetics during the first three step distances for all participants. Young adults completed a significantly longer step than old adults. During the maximum step, in general, kinetic measures were greater in the young than in the old. As step distance increased, all but one kinetic measure increased for both young and old adults. This study has shown the ability to discriminate between young and old adults, and could potentially be used in the future to distinguish between fallers and non-fallers.

  4. [C-11]raclopride-PET studies of the Huntington's disease rate of progression : Relevance of the trinucleotide repeat length

    NARCIS (Netherlands)

    Antonini, A; Leenders, KL; Eidelberg, D

    1998-01-01

    We used [C-11]raclopride and positron emission tomography (PET) to assess the relationship between striatal dopamine D2 receptor binding, trinucleotide repeat number (GAG), and subject age in 10 asymptomatic and 8 symptomatic carriers of the Huntington's disease (HD) mutation. In both preclinical an

  5. Influence of Point Count Length and Repeated Visits on Habitat Model Performance

    Science.gov (United States)

    Randy Dettmers; David A. Buehler; John G. Bartlett; Nathan A. Klaus

    1999-01-01

    Point counts are commonly used to monitor bird populations, and a substantial amount of research has investigated how conducting counts for different lengths of time affects the accuracy of these counts and the subsequent ability to monitor changes in population trends. However, little work has been done io assess how changes in count duration affect bird-habitat...

  6. Estimation of stature from arm span, arm length and tibial length among Bengalee children aged 3-11 years

    Directory of Open Access Journals (Sweden)

    B. Dorjee

    2016-05-01

    Full Text Available Background: Estimation of human stature has significant bearings on assessment of growth, nutritional status and personal identification. Often the prediction of stature from bone remains or body parts of children is complicated by the ongoing growth. Despite these disadvantages, a situation may arise where estimation of a child’s stature becomes important. In such a situation equations derived for adults cannot be applicable. Materials and Methods: The present cross-sectional study was conducted among 240 children (boys: 116; girls: 124 aged between 3 to 11 years and belonging to the Bengali Hindu Caste Population from Naxalbari, District Darjeeling, West Bengal, India. Standard procedures were followed to record stature, arm span, arm length and tibial length. Intra- and inter- observer technical errors of the measurement (TEM were calculated. One way analysis of variance (ANOVA, correlation, linear regression and stepwise regression were used to analyze the data. Result: The boys had higher mean age, mean stature, mean arm span, mean arm length and tibial length than girls. However, using ANOVA, the sex difference were not significant (p>0.05. Stature was observed to be positively and significantly correlated with all the anthropometric variables among both sexes. When stepwise regression was used, it was observed that the correlation coefficient (R and the coefficient of determination (R2 increased with inclusion of arm length and tibial length with arm span as the predictor. The addition of age as a variable further increased the predictive accuracy of the model. Predictive accuracies of the equations were higher among girls than boys. Conclusion: The present study has observed strong associations of stature with age, arm span, arm length and tibia length. The strength of prediction in general increased with the increasing number of parameters and from using linear to stepwise multiple regressions. Addition of age as a variable influenced

  7. Effect of stride length on symptoms of exercise-induced muscle damage during a repeated bout of downhill running.

    Science.gov (United States)

    Eston, R G; Lemmey, A B; McHugh, P; Byrne, C; Walsh, S E

    2000-08-01

    The purpose of this study was to assess the effects of changes in stride length on the symptoms of exercise-induced muscle damage (EIMD) during a repeated bout of downhill running in a group of 18 men and women. Muscle tenderness, plasma creatine kinase activity (CK) and maximal voluntary isometric force were measured before and after two downhill runs, with each run separated by 5 weeks. The first downhill run was at the preferred stride frequency (PSF). Participants were then randomly allocated to one of three sex-balanced groups with equal numbers of men and women: overstride (-8% PSF), understride (+8% PSF) and normal stride frequency for the second downhill run. Stride length had no effect (P>0.05) on muscle tenderness, CK or isometric peak force. Increases in muscle tenderness (Prun, although there was no difference in the pattern and extent of the strength decrement between the two runs. There were also no differences (P>0.05) in muscle tenderness, CK or the relative strength loss between the men and the women. Results suggest that the symptoms of EIMD are unaffected by gender and small alterations to the normal stride pattern during constant velocity downhill running. The observation that muscle tenderness and CK were reduced following a repeated bout of similar eccentric exercise is consistent with the phenomenon known as the 'repeated bout effect' of muscle damage.

  8. Murine protein H is comprised of 20 repeating units, 61 amino acids in length

    DEFF Research Database (Denmark)

    Kristensen, Torsten; Tack, B F

    1986-01-01

    A cDNA library constructed from size-selected (greater than 28 S) poly(A)+ RNA isolated from the livers of C57B10. WR mice was screened by using a 249-base-pair (bp) cDNA fragment encoding 83 amino acid residues of human protein H as a probe. Of 120,000 transformants screened, 30 hybridized......, 448 bp of 3'-untranslated sequence, and a polyadenylylated tail of undetermined length. Murine pre-protein H was deduced to consist of an 18-amino acid signal peptide and 1216 residues of H-protein sequence. Murine H was composed of 20 repetitive units, each about 61 amino acid residues in length...

  9. A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length.

    Science.gov (United States)

    Langbehn, D R; Brinkman, R R; Falush, D; Paulsen, J S; Hayden, M R

    2004-04-01

    Huntington's disease (HD) is a neurodegenerative disorder caused by an unstable CAG repeat. For patients at risk, participating in predictive testing and learning of having CAG expansion, a major unanswered question shifts from "Will I get HD?" to "When will it manifest?" Using the largest cohort of HD patients analyzed to date (2913 individuals from 40 centers worldwide), we developed a parametric survival model based on CAG repeat length to predict the probability of neurological disease onset (based on motor neurological symptoms rather than psychiatric onset) at different ages for individual patients. We provide estimated probabilities of onset associated with CAG repeats between 36 and 56 for individuals of any age with narrow confidence intervals. For example, our model predicts a 91% chance that a 40-year-old individual with 42 repeats will have onset by the age of 65, with a 95% confidence interval from 90 to 93%. This model also defines the variability in HD onset that is not attributable to CAG length and provides information concerning CAG-related penetrance rates.

  10. A statistical approach designed for finding mathematically defined repeats in shotgun data and determining the length distribution of clone-inserts

    DEFF Research Database (Denmark)

    Zhong, Lan; Zhang, Kunlin; Huang, Xiangang

    2003-01-01

    The large amount of repeats, especially high copy repeats, in the genomes of higher animals and plants makes whole genome assembly (WGA) quite difficult. In order to solve this problem, we tried to identify repeats and mask them prior to assembly even at the stage of genome survey. It is known...... that repeats of different copy number have different probabilities of appearance in shotgun data, so based on this principle, we constructed a statistical model and inferred criteria for mathematically defined repeats (MDRs) at different shotgun coverages. According to these criteria, we developed software......-inserts using our model. In our simulated genomes of human and rice, the length distribution of repeats is different, so their optimal length distributions of clone-inserts were not the same. Thus with optimal length distribution of clone-inserts, a given genome could be assembled better at lower coverage...

  11. Murine protein H is comprised of 20 repeating units, 61 amino acids in length

    DEFF Research Database (Denmark)

    Kristensen, Torsten; Tack, B F

    1986-01-01

    A cDNA library constructed from size-selected (greater than 28 S) poly(A)+ RNA isolated from the livers of C57B10. WR mice was screened by using a 249-base-pair (bp) cDNA fragment encoding 83 amino acid residues of human protein H as a probe. Of 120,000 transformants screened, 30 hybridized...... with this cDNA probe. Ten positives were colony-purified, and the largest plasmid cDNA insert, MH8 (4.4 kb), was sequenced by the dideoxy chain termination method. MH8 contained the complete coding sequence for the precursor of murine complement protein factor H (3702 bp), 100 bp of 5'-untranslated sequence......, 448 bp of 3'-untranslated sequence, and a polyadenylylated tail of undetermined length. Murine pre-protein H was deduced to consist of an 18-amino acid signal peptide and 1216 residues of H-protein sequence. Murine H was composed of 20 repetitive units, each about 61 amino acid residues in length...

  12. Repeat length and RNA expression level are not primary determinants in CUG expansion toxicity in Drosophila models.

    Directory of Open Access Journals (Sweden)

    Gwenn Le Mée

    Full Text Available Evidence for an RNA gain-of-function toxicity has now been provided for an increasing number of human pathologies. Myotonic dystrophies (DM belong to a class of RNA-dominant diseases that result from RNA repeat expansion toxicity. Specifically, DM of type 1 (DM1, is caused by an expansion of CUG repeats in the 3'UTR of the DMPK protein kinase mRNA, while DM of type 2 (DM2 is linked to an expansion of CCUG repeats in an intron of the ZNF9 transcript (ZNF9 encodes a zinc finger protein. In both pathologies the mutant RNA forms nuclear foci. The mechanisms that underlie the RNA pathogenicity seem to be rather complex and not yet completely understood. Here, we describe Drosophila models that might help unravelling the molecular mechanisms of DM1-associated CUG expansion toxicity. We generated transgenic flies that express inducible repeats of different type (CUG or CAG and length (16, 240, 480 repeats and then analyzed transgene localization, RNA expression and toxicity as assessed by induced lethality and eye neurodegeneration. The only line that expressed a toxic RNA has a (CTG(240 insertion. Moreover our analysis shows that its level of expression cannot account for its toxicity. In this line, (CTG(240.4, the expansion inserted in the first intron of CG9650, a zinc finger protein encoding gene. Interestingly, CG9650 and (CUG(240.4 expansion RNAs were found in the same nuclear foci. In conclusion, we suggest that the insertion context is the primary determinant for expansion toxicity in Drosophila models. This finding should contribute to the still open debate on the role of the expansions per se in Drosophila and in human pathogenesis of RNA-dominant diseases.

  13. PHOX2B polyalanine repeat length is associated with sudden infant death syndrome and unclassified sudden infant death in the Dutch population.

    Science.gov (United States)

    Liebrechts-Akkerman, Germaine; Liu, Fan; Lao, Oscar; Ooms, Ariadne H A G; van Duijn, Kate; Vermeulen, Mark; Jaddoe, Vincent W; Hofman, Albert; Engelberts, Adèle C; Kayser, Manfred

    2014-07-01

    Unclassified sudden infant death (USID) is the sudden and unexpected death of an infant that remains unexplained after thorough case investigation including performance of a complete autopsy and review of the circumstances of death and the clinical history. When the infant is below 1 year of age and with onset of the fatal episode apparently occurring during sleep, this is referred to as sudden infant death syndrome (SIDS). USID and SIDS remain poorly understood despite the identification of several environmental and some genetic risk factors. In this study, we investigated genetic risk factors involved in the autonomous nervous system in 195 Dutch USID/SIDS cases and 846 Dutch, age-matched healthy controls. Twenty-five DNA variants from 11 genes previously implicated in the serotonin household or in the congenital central hypoventilation syndrome, of which some have been associated with SIDS before, were tested. Of all DNA variants considered, only the length variation of the polyalanine repeat in exon 3 of the PHOX2B gene was found to be statistically significantly associated with USID/SIDS in the Dutch population after multiple test correction. Interestingly, our data suggest that contraction of the PHOX2B exon 3 polyalanine repeat that we found in six of 160 SIDS and USID cases and in six of 814 controls serves as a probable genetic risk factor for USID/SIDS at least in the Dutch population. Future studies are needed to confirm this finding and to understand the functional effect of the polyalanine repeat length variation, in particular contraction, in exon 3 of the PHOX2B gene.

  14. CAG repeat lengths > or =335 attenuate the phenotype in the R6/2 Huntington's disease transgenic mouse.

    Science.gov (United States)

    Dragatsis, I; Goldowitz, D; Del Mar, N; Deng, Y P; Meade, C A; Liu, Li; Sun, Z; Dietrich, P; Yue, J; Reiner, A

    2009-03-01

    With spontaneous elongation of the CAG repeat in the R6/2 transgene to > or =335, resulting in a transgene protein too large for passive entry into nuclei via the nuclear pore, we observed an abrupt increase in lifespan to >20 weeks, compared to the 12 weeks common in R6/2 mice with 150 repeats. In the > or =335 CAG mice, large ubiquitinated aggregates of mutant protein were common in neuronal dendrites and perikaryal cytoplasm, but intranuclear aggregates were small and infrequent. Message and protein for the > or =335 CAG transgene were reduced to one-third that in 150 CAG R6/2 mice. Neurological and neurochemical abnormalities were delayed in onset and less severe than in 150 CAG R6/2 mice. These findings suggest that polyQ length and pathogenicity in Huntington's disease may not be linearly related, and pathogenicity may be less severe with extreme repeats. Both diminished mutant protein and reduced nuclear entry may contribute to phenotype attenuation.

  15. Aging affects attunement in perceiving length by dynamic touch

    NARCIS (Netherlands)

    Withagen, Rob; Caljouw, Simone R.

    2011-01-01

    Earlier studies have revealed age-dependent differences in perception by dynamic touch. In the present study, we examined whether the capacity to learn deteriorates with aging. Adopting an ecological approach to learning, the authors examined the process of attunement-that is, the changes in what in

  16. Age Determination by Back Length for African Savanna Elephants: Extending Age Assessment Techniques for Aerial-Based Surveys

    Science.gov (United States)

    Trimble, Morgan J.; van Aarde, Rudi J.; Ferreira, Sam M.; Nørgaard, Camilla F.; Fourie, Johan; Lee, Phyllis C.; Moss, Cynthia J.

    2011-01-01

    Determining the age of individuals in a population can lead to a better understanding of population dynamics through age structure analysis and estimation of age-specific fecundity and survival rates. Shoulder height has been used to accurately assign age to free-ranging African savanna elephants. However, back length may provide an analog measurable in aerial-based surveys. We assessed the relationship between back length and age for known-age elephants in Amboseli National Park, Kenya, and Addo Elephant National Park, South Africa. We also compared age- and sex-specific back lengths between these populations and compared adult female back lengths across 11 widely dispersed populations in five African countries. Sex-specific Von Bertalanffy growth curves provided a good fit to the back length data of known-age individuals. Based on back length, accurate ages could be assigned relatively precisely for females up to 23 years of age and males up to 17. The female back length curve allowed more precise age assignment to older females than the curve for shoulder height does, probably because of divergence between the respective growth curves. However, this did not appear to be the case for males, but the sample of known-age males was limited to ≤27 years. Age- and sex-specific back lengths were similar in Amboseli National Park and Addo Elephant National Park. Furthermore, while adult female back lengths in the three Zambian populations were generally shorter than in other populations, back lengths in the remaining eight populations did not differ significantly, in support of claims that growth patterns of African savanna elephants are similar over wide geographic regions. Thus, the growth curves presented here should allow researchers to use aerial-based surveys to assign ages to elephants with greater precision than previously possible and, therefore, to estimate population variables. PMID:22028925

  17. Age determination by back length for African savanna elephants: extending age assessment techniques for aerial-based surveys.

    Directory of Open Access Journals (Sweden)

    Morgan J Trimble

    Full Text Available Determining the age of individuals in a population can lead to a better understanding of population dynamics through age structure analysis and estimation of age-specific fecundity and survival rates. Shoulder height has been used to accurately assign age to free-ranging African savanna elephants. However, back length may provide an analog measurable in aerial-based surveys. We assessed the relationship between back length and age for known-age elephants in Amboseli National Park, Kenya, and Addo Elephant National Park, South Africa. We also compared age- and sex-specific back lengths between these populations and compared adult female back lengths across 11 widely dispersed populations in five African countries. Sex-specific Von Bertalanffy growth curves provided a good fit to the back length data of known-age individuals. Based on back length, accurate ages could be assigned relatively precisely for females up to 23 years of age and males up to 17. The female back length curve allowed more precise age assignment to older females than the curve for shoulder height does, probably because of divergence between the respective growth curves. However, this did not appear to be the case for males, but the sample of known-age males was limited to ≤27 years. Age- and sex-specific back lengths were similar in Amboseli National Park and Addo Elephant National Park. Furthermore, while adult female back lengths in the three Zambian populations were generally shorter than in other populations, back lengths in the remaining eight populations did not differ significantly, in support of claims that growth patterns of African savanna elephants are similar over wide geographic regions. Thus, the growth curves presented here should allow researchers to use aerial-based surveys to assign ages to elephants with greater precision than previously possible and, therefore, to estimate population variables.

  18. Topological diversity of chromatin fibers: Interplay between nucleosome repeat length, DNA linking number and the level of transcription

    Directory of Open Access Journals (Sweden)

    Davood Norouzi

    2015-11-01

    Full Text Available The spatial organization of nucleosomes in 30-nm fibers remains unknown in detail. To tackle this problem, we analyzed all stereochemically possible configurations of two-start chromatin fibers with DNA linkers L = 10-70 bp (nucleosome repeat length NRL = 157-217 bp. In our model, the energy of a fiber is a sum of the elastic energy of the linker DNA, steric repulsion, electrostatics, and the H4 tail-acidic patch interaction between two stacked nucleosomes. We found two families of energetically feasible conformations of the fibers—one observed earlier, and the other novel. The fibers from the two families are characterized by different DNA linking numbers—that is, they are topologically different. Remarkably, the optimal geometry of a fiber and its topology depend on the linker length: the fibers with linkers L = 10n and 10n + 5 bp have DNA linking numbers per nucleosome DLk >>-1.5 and -1.0, respectively. In other words, the level of DNA supercoiling is directly related to the length of the inter-nucleosome linker in the chromatin fiber (and therefore, to NRL. We hypothesize that this topological polymorphism of chromatin fibers may play a role in the process of transcription, which is known to generate different levels of DNA supercoiling upstream and downstream from RNA polymerase. A genome-wide analysis of the NRL distribution in active and silent yeast genes yielded results consistent with this assumption.

  19. Utility of telomere length measurements for age determination of humpback whales

    Directory of Open Access Journals (Sweden)

    Morten Tange Olsen

    2014-12-01

    Full Text Available This study examines the applicability of telomere length measurements by quantitative PCR as a tool for minimally invasive age determination of free-ranging cetaceans. We analysed telomere length in skin samples from 28 North Atlantic humpback whales (Megaptera novaeangliae, ranging from 0 to 26 years of age. The results suggested a significant correlation between telomere length and age in humpback whales. However, telomere length was highly variable among individuals of similar age, suggesting that telomere length measured by quantitative PCR is an imprecise determinant of age in humpback whales. The observed variation in individual telomere length was found to be a function of both experimental and biological variability, with the latter perhaps reflecting patterns of inheritance, resource allocation trade-offs, and stochasticity of the marine environment.

  20. Direct and accurate measurement of CAG repeat configuration in the ataxin-1 (ATXN-1) gene by "dual-fluorescence labeled PCR-restriction fragment length analysis".

    Science.gov (United States)

    Lin, Jiang X; Ishikawa, Kinya; Sakamoto, Masaki; Tsunemi, Taiji; Ishiguro, Taro; Amino, Takeshi; Toru, Shuta; Kondo, Ikuko; Mizusawa, Hidehiro

    2008-01-01

    Spinocerebellar ataxia type 1 (SCA1; OMIM: #164400) is an autosomal dominant cerebellar ataxia caused by an expansion of CAG repeat, which encodes polyglutamine, in the ataxin-1 (ATXN1) gene. Length of polyglutamine in the ATXN1 protein is the critical determinant of pathogenesis of this disease. Molecular diagnosis of SCA1 is usually undertaken by assessing the length of CAG repeat configuration using primers spanning this configuration. However, this conventional method may potentially lead to misdiagnosis in assessing polyglutamine-encoding CAG repeat length, since CAT interruptions may be present within the CAG repeat configuration, not only in normal controls but also in neurologically symptomatic subjects. We developed a new method for assessing actual CAG repeat numbers not interrupted by CAT sequences. Polymerase chain reaction using a primer pair labeled with two different fluorescences followed by restriction enzyme digestion with SfaNI which recognizes the sequence "GCATC(N)(5)", lengths of actual CAG repeats that encode polyglutamine were directly detected. We named this method "dual fluorescence labeled PCR-restriction fragment length analysis". We found that numbers of actual CAG repeat encoding polyglutamine do not overlap between our cohorts of normal chromosomes (n=385) and SCA1 chromosomes (n=5). We conclude that the present method is a useful way for molecular diagnosis of SCA1.

  1. A Statistical Approach Designed for Finding Mathematically Defined Repeats in Shotgun Data and Determining the Length Distribution of Clone—Inserts

    Institute of Scientific and Technical Information of China (English)

    LanZhong; KunlinZhang; XiangangHuang; PeixiangNi; YujunHan; KaiWang; JunWang; SonggangLi

    2003-01-01

    The large amount of repeats,especially high copy repeats,in the genomes of higher animals and plants makes whole genome assembly(WGA)quite difficult.In order to solve this problem,we tried to identify repeats and mask them prior to assembly even at the stage of genome survey.It is known that repeats of different copy number have different probabilities of appearance in shotgun data,so based on this principle,we constructed a statistical model and inferred criteria for mathematically defined repeats(MDRs)at different shotgun coverages.According to these criteria,we developed software MDRmasker to identify and mask MDRs in shotgun data.With repeats masked prior to assembly,the speed of as sembly was increased with lower error probability.In addition,clone-insert size affects the accuracy of repeat assembly and scaffold construction.We also designed length distribution of clone-inserts using our model.In our simulated genomes of human and rice,the length distribution of repeats in different,so their optimal length distributions of clone-inserts were not the same.Thus with optimal length distribution of clone-inserts,a given genome could be assembled better at lower coverage.

  2. A Statistical Approach Designed for Finding Mathematically De fined Repeats in Shotgun Data and Determining the Length Distri bution of Clone-Inserts

    Institute of Scientific and Technical Information of China (English)

    Lan Zhong; Kunlin Zhang; Xiangang Huang; Peixiang Ni; Yujun Han; Kai Wang; Jun Wang; Songgang Li

    2003-01-01

    The large amount of repeats, especially high copy repeats, in the genomes of higher animals and plants makes whole genome assembly (WGA) quite difficult. In order to solve this problem, we tried to identify repeats and mask them prior to assembly even at the stage of genome survey. It is known that repeats of different copy number have different probabilities of appearance in shotgun data, so based on this principle, we constructed a statistical model and inferred criteria for mathematically defined repeats (MDRs) at different shotgun coverages. According to these criteria, we developed software MDRmasker to identify and mask MDRs in shotgun data. With repeats masked prior to assembly, the speed of assembly was increased with lower error probability. In addition, clone-insert size affects the accuracy of repeat assembly and scaffold construction. We also designed length distribution of clone-inserts using our model. In our simulated genomes of human and rice, the length distribution of repeats is different, so their optimal length distributions of clone-inserts were not the same. Thus with optimal length distribution of clone-inserts, a given genome could be assembled better at lower coverage.

  3. Size polymorphism of chicken major histocompatibility complex-encoded B-G molecules is due to length variation in the cytoplasmic heptad repeat region

    DEFF Research Database (Denmark)

    Kaufman, J; Salomonsen, J; Skjødt, K;

    1990-01-01

    that the extracellular regions of these molecules are very similar and that the length polymorphism is due to variations in the cytoplasmic regions. Inspection of the cDNA-derived protein sequence in this region shows many heptad repeats, which may allow variation in length by step deletion and alternative splicing...

  4. Exploring the relationship between age and tenure with length of disability

    Science.gov (United States)

    Young, Amanda E.; Pransky, Glenn

    2015-01-01

    Background The aging of the workforce, coupled with the changing nature of career tenure has raised questions about the impact of these trends on work disability. This study aimed to determine if age and tenure interact in relating to work disability duration. Methods Relationships were investigated using random effects models with 239,359 work disability claims occurring between 2008 and 2012. Results A 17‐day difference in the predicted length of disability was observed from ages 25 to 65. Tenure moderated the relationship between age and length of disability. At younger ages, the length of disability decreased as tenure increased, but at older age, the length of disability increased as tenure increased. Discussion Results indicate that although there is a relationship between length of disability and tenure, age makes a greater unique contribution to explaining variance in length of disability. Future research is needed to better understand why specifically age shows a strong relationship with length of disability and why that relationship varies with age. Am. J. Ind. Med. 58:974–987, 2015. © 2015 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals, Inc. PMID:26010587

  5. Analysis of the age of Panax ginseng based on telomere length and telomerase activity.

    Science.gov (United States)

    Liang, Jiabei; Jiang, Chao; Peng, Huasheng; Shi, Qinghua; Guo, Xiang; Yuan, Yuan; Huang, Luqi

    2015-01-23

    Ginseng, which is the root of Panax ginseng (Araliaceae), has been used in Oriental medicine as a stimulant and dietary supplement for more than 7,000 years. Older ginseng plants are substantially more medically potent, but ginseng age can be simulated using unscrupulous cultivation practices. Telomeres progressively shorten with each cell division until they reach a critical length, at which point cells enter replicative senescence. However, in some cells, telomerase maintains telomere length. In this study, to determine whether telomere length reflects ginseng age and which tissue is best for such an analysis, we examined telomerase activity in the main roots, leaves, stems, secondary roots and seeds of ginseng plants of known age. Telomere length in the main root (approximately 1 cm below the rhizome) was found to be the best indicator of age. Telomeric terminal restriction fragment (TRF) lengths, which are indicators of telomere length, were determined for the main roots of plants of different ages through Southern hybridization analysis. Telomere length was shown to be positively correlated with plant age, and a simple mathematical model was formulated to describe the relationship between telomere length and age for P. ginseng.

  6. A correlation study of telomere length in peripheral blood leukocytes and kidney function with age.

    Science.gov (United States)

    Zhang, Wei-Guang; Wang, Yong; Hou, Kai; Jia, Lin-Pei; Ma, Jie; Zhao, De-Long; Zhu, Shu-Ying; Bai, Xiao-Juan; Cai, Guang-Yan; Wang, Yan-Ping; Sun, Xue-Feng; Chen, Xiang-Mei

    2015-06-01

    The current study aimed to investigate the association between telomere length in peripheral blood leukocytes and kidney function in various age groups of a healthy population. A total of 139 healthy individuals were divided into five groups according to their age: 35‑44, 45‑54, 55‑64, 65‑74 and >75 years old. Peripheral blood leukocytes were obtained and the telomere restriction fragment (TRF) length was assayed using a digoxigenin‑labeled hybridization probe in Southern blot assays. Laboratory assays of kidney function were also performed. A correlation was observed between TRF length and age (r=‑0.314, Ptelomere length of the individuals >75 years group being significantly shorter than the telomere length of the 35‑44, 45‑54 and 55‑64 years age groups (Plength for males versus females did not differ for any of the age groups, while a correlation was observed between TRF length and serum levels of cystatin C (r=‑0.195, Plength and glomerular filtration rate (r=‑0.184, Ptelomere length reduced with age and was correlated with serum levels of cystatin C and glomerular filtration rate. Therefore, TRF length is associated with kidney function and may serve as a marker of aging.

  7. Regulation of the nucleosome repeat length in vivo by the DNA sequence, protein concentrations and long-range interactions.

    Directory of Open Access Journals (Sweden)

    Daria A Beshnova

    2014-07-01

    Full Text Available The nucleosome repeat length (NRL is an integral chromatin property important for its biological functions. Recent experiments revealed several conflicting trends of the NRL dependence on the concentrations of histones and other architectural chromatin proteins, both in vitro and in vivo, but a systematic theoretical description of NRL as a function of DNA sequence and epigenetic determinants is currently lacking. To address this problem, we have performed an integrative biophysical and bioinformatics analysis in species ranging from yeast to frog to mouse where NRL was studied as a function of various parameters. We show that in simple eukaryotes such as yeast, a lower limit for the NRL value exists, determined by internucleosome interactions and remodeler action. For higher eukaryotes, also the upper limit exists since NRL is an increasing but saturating function of the linker histone concentration. Counterintuitively, smaller H1 variants or non-histone architectural proteins can initiate larger effects on the NRL due to entropic reasons. Furthermore, we demonstrate that different regimes of the NRL dependence on histone concentrations exist depending on whether DNA sequence-specific effects dominate over boundary effects or vice versa. We consider several classes of genomic regions with apparently different regimes of the NRL variation. As one extreme, our analysis reveals that the period of oscillations of the nucleosome density around bound RNA polymerase coincides with the period of oscillations of positioning sites of the corresponding DNA sequence. At another extreme, we show that although mouse major satellite repeats intrinsically encode well-defined nucleosome preferences, they have no unique nucleosome arrangement and can undergo a switch between two distinct types of nucleosome positioning.

  8. Genetic, environmental and phenotypic relationships among gestation length, birth weight, growth traits and age at first calving in beef cattle.

    Science.gov (United States)

    Bourdon, R M; Brinks, J S

    1982-09-01

    Data on the Red Angus, Angus and Hereford herds of Pioneer Hi-Bred International, Inc., Des Moines, Iowa, collected from 1968 to 1976, were analyzed for relationships among gestation length, birth weight, prenatal gain (birth weight adjusted for gestation length), growth traits and age at first calving. A total of 5,691 calf records, 1,783 listing gestation length, were included in the study. Paternal half-sib analyses and least-squares procedures were used to compute heritability estimates and genetic, environmental and phenotypic correlations among traits. Genetic correlations among growth traits, including prenatal gain, were high in all cases. Heritability estimates for gestation length and birth weight were .36 and .43, respectively, for bull calves and .37 and .35 for heifer calves. Genetic correlations between these traits were .25 and .22 for bull and heifer calves, respectively. Gestation length was negatively correlated (genetically) with all growth traits except birth weight. This result suggests that faster growing fetuses may trigger parturition earlier than average. Age at first calving was negatively correlated (genetically) with growth traits, indicating a favorable relationship between growth and early reproduction. Analysis of several selection indexes combining either birth weight and yearling weight or gestation length and yearling weight indicated that continued response to selection for growth without excessive increase in birth weight is feasible. Selection for growth and moderate birth weight would be more effective than selection for growth and shorter gestation, suggesting that the former method would both shorten gestation and alter the growth curve. Repeatability estimates for gestation length and birth weight were .20 and .22, respectively. Maternal effects accounted for approximately 10% of the variation in each trait.

  9. Estimation of age structure of fish populations from length-frequency data

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, K.D.; Adams, S.M.

    1977-01-01

    A probability model is presented to determine the age structure of a fish population from length-frequency data. It is shown that when the age-length key is available, maximum-likelihood estimates of the age structure can be obtained. When the key is not available, approximate estimates of the age structure can be obtained. The model is used for determination of the age structure of populations of channel catfish and white crappie. Practical applications of the model to impact assessment are discussed.

  10. Leukocyte telomere length and physical ability among Danish twins age 70+

    DEFF Research Database (Denmark)

    Bendix, Laila; Gade, Maria Monrad; Staun, Pia Wirenfeldt;

    2011-01-01

    Leukocyte telomere length (LTL) shortens with age and is potentially a biomarker of human aging. We examined the relation of LTL with physical ability and cognitive function in 548 same-sex twins from the Longitudinal Study of Aging Danish Twins. LTL was measured by Southern blots of the terminal...

  11. Telomere Length in Aged Mayak PA Nuclear Workers Chronically Exposed to Internal Alpha and External Gamma Radiation.

    Science.gov (United States)

    Scherthan, Harry; Sotnik, Natalia; Peper, Michel; Schrock, Gerrit; Azizova, Tamara; Abend, Michael

    2016-06-01

    Telomeres consist of GC-rich DNA repeats and the "shelterin" protein complex that together protect chromosome ends from fusion and degradation. Telomeres shorten with age due to incomplete end replication and upon exposure to environmental and intrinsic stressors. Exposure to ionizing radiation is known to modulate telomere length. However, the response of telomere length in humans chronically exposed to radiation is poorly understood. Here, we studied relative telomere length (RTL) by IQ-FISH to leukocyte nuclei in a group of 100 workers from the plutonium production facility at the Mayak Production Association (PA) who were chronically exposed to alpha-emitting ((239)Pu) radiation and/or gamma (photon) radiation, and 51 local residents serving as controls, with a similar mean age of about 80 years. We applied generalized linear statistical models adjusted for age at biosampling and the second exposure type on a linear scale and observed an age-dependent telomere length reduction. In those individuals with the lowest exposure, a significant reduction of about 20% RTL was observed, both for external gamma radiation (≤1 Gy) and internal alpha radiation (≤0.05-0.1 Gy to the red bone marrow). In highly exposed individuals (>0.1 Gy alpha, 1-1.5 Gy gamma), the RTL was similar to control. Stratification by gender revealed a significant (∼30%) telomere reduction in low-dose-exposed males, which was absent in females. While the gender differences in RTL may reflect different working conditions, lifestyle and/or telomere biology, absence of a dose response in the highly exposed individuals may reflect selection against cells with short telomeres or induction of telomere-protective effects. Our observations suggest that chronic systemic exposure to radiation leads to variable dose-dependent effects on telomere length.

  12. Dynamics of telomere length in different age groups in a Latvian population.

    Science.gov (United States)

    Zole, Egija; Pliss, Liana; Ranka, Renate; Krumina, Astrida; Baumanis, Viesturs

    2013-12-01

    The shortening of telomeres with ageing is a well-documented observation; however, the reported number of nucleotides in telomeres varies between different laboratories and studies. Such variability is likely caused by ethnic differences between the populations studied. Until now, there were no studies that investigated the variability of telomere length in a senescent Latvian population of the most common mitochondrial haplogroups, defined as H (45%), U (25%), Y chromosomal N1c (40%) and R1a1 (40%). Telomere length was determined in 121 individuals in different age groups, including a control group containing individuals of 20-40 years old and groups of individuals between 60-70 years old, 71-80 years old, 81-90 years old, and above 90 years old. Telomere length was determined using the Southern blot telomeric restriction fragment assay (TRF). Decreased telomere length with ageing was confirmed, but a comparison of centenarians and individuals between 60-90 years of age did not demonstrate a significant difference in telomere length. However, significant variability in telomere length was observed in the control group, indicating probable rapid telomere shortening in some individuals that could lead up to development of health status decline appearing with ageing. Telomere length measured in mononuclear blood cells (MNC) was compared with the telomere length measured in whole peripheral white blood cells (WBC) using TRF. Telomere length in MNC was longer than in WBC for the control group with individuals 20 to 40 years old; in contrast, for the group of individuals aged 65 to 85 years old, measured telomere length was shorter in MNC when compared to WBC.

  13. Skin pentosidine and telomere length do not covary with age in a long-lived seabird.

    Science.gov (United States)

    Rattiste, Kalev; Klandorf, Hillar; Urvik, Janek; Sepp, Tuul; Asghar, Muhammad; Hasselquist, Dennis; Cooey, Crissa; Hõrak, Peeter

    2015-08-01

    The questions about why and how senescence occurs in the wild are among the most pertinent ones in evolutionary ecology. Telomere length is a commonly used marker for aging, while other biomarkers of aging have received considerably less attention. Here we studied how another potent indicator of aging-skin pentosidine concentration-relates to age and blood telomere length in a long-lived seabird with well-documented reproductive senescence. We found no associations between telomere length, skin pentosidine and chronological age in male common gulls (Larus canus), aging from 2 to 30 years. However, the variance in telomere length was 4.6 times higher among the birds older than 13 years, which hints at relaxed selection on telomere length among the birds that have passed their prime age of reproduction. These results suggest that physiological and chronological ages may be largely uncoupled in our study system. Furthermore, our findings do not support a hypothesis about the presence of a common physiological factor (e.g., such as oxidative stress) that would cause covariation between two independent markers of aging.

  14. Age-related gestation length adjustment in a large iteroparous mammal at northern latitude.

    Science.gov (United States)

    Mysterud, Atle; Røed, Knut H; Holand, Øystein; Yoccoz, Nigel G; Nieminen, Mauri

    2009-09-01

    1. There is considerable interest in patterns of age-dependent reproductive effort and reproductive timing of large iteroparous mammals living in strongly seasonal environments. Due to lack of data on both timing of mating and birth, there is generally little insight into whether variation in gestation length play a role for life-history patterns observed for large mammals at northern latitudes. 2. Based on data on both timing of mating and birth of 88 female reindeer (and paternity confirmed with DNA fingerprinting), we explore the view that adjustment of gestation length plays a role in the reproductive tactic. 3. Observed gestation lengths of reindeer varied between 211 and 229 days (mean of 221 days). Consistent with a dynamic view of gestation length, variation could be predicted from life-history traits. Gestation length was longer for male than female offspring, which is expected in polygynous species where males benefit more from extra allocation of maternal resources. Gestation length increased with maternal age both due to direct effects and indirect effects linked to earlier mating of older, heavier females. Early mating females increased gestation length. A relatively small effect of female age on birth mass operated through variation in gestation length. 4. Our analysis supports the view that adjustment of gestation length is a part of the reproductive tactic of large mammals in northern environments.

  15. FETAL GESTATIONAL AGE ESTIMATION BY FETAL FOOT LENGTH MEASUREMENT AND FETAL FEMUR TO FOOT LENGTH RATIO IN INDIAN POPULATION - A PROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Mukta

    2014-03-01

    Full Text Available BACKGROUND: Multiple parameters are in use for the accurate assessment of the gestational age by ultrasound, but the literature suggests that fetal foot length can be used to estimate gestational age, when other parameters are not available for measurement. Foetal femur/ foot length ratio can help in differentiating the foeti that have dysplastic limb reduction, from those whose limbs are short because of constitutional factors/IUGR. A prospective study was done to measure the fetal foot length for gestational age and to evaluate fetal femur to foot length ratio in pregnant women of 16-37 weeks gestation. MATERIALS & METHOD: One hundred and three normal singleton pregnant women of 16-37 weeks gestation were examined for routine obstetrics ultrasound. In these patients fetal foot length measurements were taken and the gestational age was assessed. In addition, fetal femur length to foot length ratio was calculated in each patient. RESULTS/OBSERVATION: Linear relationship between foot length and gestational age was present with a R2 value of 0.90 (p < than 0.001 and the fetal femur length/foot length ratio was found to be more than or equal to 0.92.The foot length can be a reliable parameter for use in assessment of gestational age and as most skeletal dysplasias spare the feet, the fetal femur length/foot length ratio can be used to detect most skeletal dysplasia. CONCLUSIONS: Foetal foot length is a reliable parameter for assessment of gestational age and femur length/foot length ratio is approximately 1 and a ratio of < 0.92 shall be useful in the detection of most skeletal dysplasia.

  16. Egg length of Anastrepha obliqua Macquart (Diptera, Tephritidae according to oviposition rate and maternal age

    Directory of Open Access Journals (Sweden)

    Isabel C. Boleli

    1992-01-01

    Full Text Available The length of the entire egg, micropile and vitellus regions of Anastrepha obliqua Macquart, 1835 were measured during all opposition period. Obtained values were compared among them and with oviposition rate. The smallest eggs were produced during the first 35 oviposition days, period where the highest oviposition rate occured. The decrease in egg length was found to be due to a descrease in the vitellus region. Micropile length was found to be pratically constant throughout oviposition. Furthermore, no relationship between maternal age and length was detectable.

  17. Paternal age and telomere length in twins: the germ stem cell selection paradigm.

    Science.gov (United States)

    Hjelmborg, Jacob B; Dalgård, Christine; Mangino, Massimo; Spector, Tim D; Halekoh, Ulrich; Möller, Sören; Kimura, Masayuki; Horvath, Kent; Kark, Jeremy D; Christensen, Kaare; Kyvik, Kirsten O; Aviv, Abraham

    2015-08-01

    Telomere length, a highly heritable trait, is longer in offspring of older fathers. This perplexing feature has been attributed to the longer telomeres in sperm of older men and it might be an 'epigenetic' mechanism through which paternal age plays a role in telomere length regulation in humans. Based on two independent (discovery and replication) twin studies, comprising 889 twin pairs, we show an increase in the resemblance of leukocyte telomere length between dizygotic twins of older fathers, which is not seen in monozygotic twins. This phenomenon might result from a paternal age-dependent germ stem cell selection process, whereby the selected stem cells have longer telomeres, are more homogenous with respect to telomere length, and share resistance to aging.

  18. Age-related differences in repeated-sprint ability in highly trained youth football players.

    Science.gov (United States)

    Mujika, Inigo; Spencer, Matt; Santisteban, Juanma; Goiriena, Juan Jose; Bishop, David

    2009-12-01

    In this study, we investigated the age-related differences in repeated-sprint ability and blood lactate responses in 134 youth football players. Players from the development programme of a professional club were grouped according to their respective under-age team (U-11 to U-18). Following familiarization, the participants performed a repeated-sprint ability test [6 x 30-m sprints 30 s apart, with active recovery (2.0-2.2 m . s(-1)) between sprints]. The test variables were total time, percent sprint decrement, and post-test peak lactate concentration. Total time improved from the U-11 to U-15 age groups (range 33.15 +/- 1.84 vs. 27.25 +/- 0.82 s), whereas no further significant improvements were evident from U-15 to U-18. No significant differences in percent sprint decrement were reported among groups (range 4.0 +/- 1.0% to 5.5 +/- 2.1%). Post-test peak lactate increased from one age group to the next (range 7.3 +/- 1.8 to 12.6 +/- 1.6 mmol . l(-1)), but remained constant when adjusted for age-related difference in body mass. Peak lactate concentration was moderately correlated with sprint time (r = 0.70, P > 0.001). Our results suggest that performance in repeated-sprint ability improves during maturation of highly trained youth football players, although a plateau occurs from 15 years of age. In contrast to expectations based on previous suggestions, percent sprint decrement during repeated sprints did not deteriorate with age.

  19. Viral delivery of C9orf72 hexanucleotide repeat expansions in mice leads to repeat-length-dependent neuropathology and behavioural deficits

    Directory of Open Access Journals (Sweden)

    Saul Herranz-Martin

    2017-07-01

    Full Text Available Intronic GGGGCC repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD. Two major pathologies stemming from the hexanucleotide RNA expansions (HREs have been identified in postmortem tissue: intracellular RNA foci and repeat-associated non-ATG dependent (RAN dipeptides, although it is unclear how these and other hallmarks of disease contribute to the pathophysiology of neuronal injury. Here, we describe two novel lines of mice that overexpress either 10 pure or 102 interrupted GGGGCC repeats mediated by adeno-associated virus (AAV and recapitulate the relevant human pathology and disease-related behavioural phenotypes. Similar levels of intracellular RNA foci developed in both lines of mice, but only mice expressing 102 repeats generated C9orf72 RAN pathology, neuromuscular junction (NMJ abnormalities, dispersal of the hippocampal CA1, enhanced apoptosis, and deficits in gait and cognition. Neither line of mice, however, showed extensive TAR DNA-binding protein 43 (TDP-43 pathology or neurodegeneration. Our data suggest that RNA foci pathology is not a good predictor of C9orf72 RAN dipeptide formation, and that RAN dipeptides and NMJ dysfunction are drivers of C9orf72 disease pathogenesis. These AAV-mediated models of C9orf72-associated ALS/FTD will be useful tools for studying disease pathophysiology and developing new therapeutic approaches.

  20. Tandem repeat sequence variation and length heteroplasmy in the mitochondrial DNA D-loop of the threatened Gulf of Mexico sturgeon, Acipenser oxyrhynchus desotoi.

    Science.gov (United States)

    Miracle, A L; Campton, D E

    1995-01-01

    Genetic variability within the Suwannee River, Florida, population of Gulf of Mexico sturgeon, Acipenser oxyrhynchus desotoi, was assessed by examining sequence and length variation within the control region, or D-loop, of the mitochondrial genome. Although once abundant throughout the Gulf of Mexico, Gulf sturgeon are now listed as a threatened species by the U.S. Fish and Wildlife Service. Mitochondrial DNA was analyzed for length variation from 168 individual Gulf sturgeon by PCR amplification and visualization of PCR products using ethidium bromide-stained agarose gels. Of the 168 individual Gulf sturgeon, 31 (18.5%) were heteroplasmic for one to four copies of an 81-base pair, tandemly repeated sequence in the D-loop region. However, no individuals homoplasmic for multiple copies of the repeat sequence were observed. The existence and nature of these tandem repeats in heteroplasmic individuals was confirmed by direct sequencing of the PCR products for a subset of 22 individuals. The results are consistent with the apparent nature and mechanism of heteroplasmy observed in a congeneric species, A. transmontanus. In addition, sequences for 187 base pairs outside of the tandem repeats were identical among all 16 individuals assayed for this region. Lack of variable sequences is concordant with earlier studies involving mtDNA restriction fragment length profiles of Gulf sturgeon found in the Suwannee River. The absence of sequence variation exclusive of the tandem repeats is consistent with the hypothesis that the subspecies has undergone a population or evolutionary bottleneck.

  1. Clustering of Beijing genotype Mycobacterium tuberculosis isolates from the Mekong delta in Vietnam on the basis of variable number of tandem repeat versus restriction fragment length polymorphism typing.

    NARCIS (Netherlands)

    Huyen, M.N.; Kremer, K.; Lan, N.T.; Buu, T.N.; Cobelens, F.G.; Tiemersma, E.W.; Haas, P. de; Soolingen, D. van

    2013-01-01

    BACKGROUND: In comparison to restriction fragment length polymorphism (RFLP) typing, variable number of tandem repeat (VNTR) typing is easier to perform, faster and yields results in a simple, numerical format. Therefore, this technique has gained recognition as the new international gold standard i

  2. Influence of age and length of service on the level of stress and burnout syndrome.

    Science.gov (United States)

    Stanetić, Kosana; Tesanović, Gordana

    2013-01-01

    The burnout syndrome is a response to chronic emotional and interpersonal stressors which are related to workplace. Medicine is one of the professions at the greatest risk of suffering from burnout syndrome. The aim of this study was to assess the presence of stress and burnout syndrome in relation with age and length of service in the family medicine physicians in the Republic of Srpska. The study was carried out on the basis of a questionnaire survey among family medicine physicians in seven Primary Health Care Centres in the Republic of Srpska from February 1st to April 30th 2010. The participants fulfilled the questionnaire for self-assessment of stress level and the Maslach Burnout Inventory, which were amended with data regarding age, sex, length of service and educational and vocational level. The study included 199 (83.3%) female and 40 (16.7%) male participants. The physicians aged over 46 years and with the length of service over 21 years had statistically significant higher level of stress and emotional exhaustion than younger participants and participants with shorter length of service. Age and length of service have important influence on the level of stress and burnout syndrome: the older the physicians and the higher the length of service the higher the level of stress and the higher the risk of burnout syndrome.

  3. Does Relative Age Affect Career Length in North American Professional Sports?

    Science.gov (United States)

    Steingröver, C; Wattie, N; Baker, J; Schorer, J

    Relative age effects (RAEs) typically favour older members within a cohort; however, research suggests that younger players may experience some long-term advantages, such as longer career length. The purposes of this study were to replicate previous findings on RAEs among National Hockey League (NHL) ice hockey players, National Basketball Association (NBA) basketball players and National Football League (NFL) football players and to investigate the influence of relative age on career length in all three sports. Using official archives, birthdates and number of games played were collected for players drafted into the NBA (N = 407), NFL (N = 2380) and NHL (N = 1028) from 1980 to 1989. We investigated the possibility that younger players might be able to maximize their career length by operationalizing career length as players' number of games played throughout their careers. There was a clear RAE for the NHL, but effects were not significant for the NBA or NFL. Moreover, there was a significant difference in matches played between birth quartiles in the NHL favouring relatively younger players. There were no significant quartiles by career length effects in the NBA or NFL. The significant relationship between relative age and career length provides further support for relative age as an important constraint on expertise development in ice hockey but not basketball or football. Currently, the reason why relatively younger players have longer careers is not known. However, it may be worth exploring the influence of injury risk or the development of better playing skills.

  4. Non-linear association between androgen receptor CAG and GGN repeat lengths and reproductive parameters in fertile European and Inuit men.

    Science.gov (United States)

    Brokken, L J S; Rylander, L; Jönsson, B A; Spanò, M; Pedersen, H S; Ludwicki, J K; Zviezdai, V; Bizzaro, D; Manicardi, G C; Toft, G; Bonde, J P; Giwercman, A; Lundberg Giwercman, Y

    2013-05-06

    Recently the dogma that there is an inverse linear association between androgen receptor (AR) CAG and GGN polymorphisms and receptor activity has been challenged. We analysed the pattern of association between 21 male reproductive phenotypes and AR CAG/GGN repeat lengths in 557 proven-fertile men. A linear association was only found between sperm DNA fragmentation index (DFI) and CAG length, and between inhibin B and GGN length. Men with longer CAG then the reference (22-24), had higher oestradiol levels, whereas men with shorter CAG stretches had a higher DFI and a higher proportion of Fas-positive germ cells. Subjects with either short or long CAG had increased seminal levels of prostate-specific antigen and neutral α-glucosidase activity. Compared to men with the median GGN length of 23, those with shorter GGN repeats had higher levels of inhibin B, higher proportions of normal and progressive sperm, and a higher fraction of Fas-positive sperm, while men with longer GGN had higher oestradiol levels. These data indicate that at least for some markers of male reproductive function the association with CAG or GGN repeat length is curvilinear.

  5. Heterogenous effect of androgen receptor CAG tract length on testicular germ cell tumor risk: shorter repeats associated with seminoma but not other histologic types

    Science.gov (United States)

    Davis-Dao, Carol A.; Siegmund, Kimberly D.; Vandenberg, David J.; Skinner, Eila C.; Coetzee, Gerhard A.; Thomas, Duncan C.; Pike, Malcolm C.; Cortessis, Victoria K.

    2011-01-01

    Increasing rates of testicular germ cells tumors (TGCTs) overtime suggest that environmental factors are involved in disease etiology, but familial risk and genome-wide association studies implicate genetic factors as well. We investigated whether variation in the functional CAGn polymorphism in the androgen receptor (AR) gene is associated with TGCT risk, using data from a population-based family study. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association of CAG repeat length and TGCT risk using matched pairs logistic regression. Analyses of 273 TGCT case–mother pairs revealed no association between AR CAG repeat length and overall TGCT risk. However, risk of seminoma was significantly associated with shorter CAG repeat length [CAG 20–21 versus CAG ≤ 19: OR = 0.82 (95% CI: 0.43–1.58), CAG 22–23 versus CAG ≤ 19: OR = 0.39 (95% CI: 0.19–0.83) and CAG ≥ 24 versus CAG ≤ 19: OR = 0.42 (95% CI: 0.20–0.86)], with a highly significant trend over these four categories of decreasing CAG repeat length (Ptrend = 0.0030). This is the first report of a statistically significant association between AR CAG repeat length and seminoma risk, suggesting that increased AR transactivation may be involved in development of seminoma and/or progression of carcinoma in situ/intratubular germ cell neoplasia unclassified to seminoma. This result provides a rationale whereby androgenic environmental compounds could contribute to increases in TGCT incidence, and identifies for the first time a potential biological pathway influencing whether TGCTs achieve seminomatous versus nonseminomatous histology, a clinically and biologically important distinction. PMID:21642359

  6. Heterogenous effect of androgen receptor CAG tract length on testicular germ cell tumor risk: shorter repeats associated with seminoma but not other histologic types.

    Science.gov (United States)

    Davis-Dao, Carol A; Siegmund, Kimberly D; Vandenberg, David J; Skinner, Eila C; Coetzee, Gerhard A; Thomas, Duncan C; Pike, Malcolm C; Cortessis, Victoria K

    2011-08-01

    Increasing rates of testicular germ cells tumors (TGCTs) overtime suggest that environmental factors are involved in disease etiology, but familial risk and genome-wide association studies implicate genetic factors as well. We investigated whether variation in the functional CAG(n) polymorphism in the androgen receptor (AR) gene is associated with TGCT risk, using data from a population-based family study. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association of CAG repeat length and TGCT risk using matched pairs logistic regression. Analyses of 273 TGCT case-mother pairs revealed no association between AR CAG repeat length and overall TGCT risk. However, risk of seminoma was significantly associated with shorter CAG repeat length [CAG 20-21 versus CAG ≤ 19: OR = 0.82 (95% CI: 0.43-1.58), CAG 22-23 versus CAG ≤ 19: OR = 0.39 (95% CI: 0.19-0.83) and CAG ≥ 24 versus CAG ≤ 19: OR = 0.42 (95% CI: 0.20-0.86)], with a highly significant trend over these four categories of decreasing CAG repeat length (P(trend) = 0.0030). This is the first report of a statistically significant association between AR CAG repeat length and seminoma risk, suggesting that increased AR transactivation may be involved in development of seminoma and/or progression of carcinoma in situ/intratubular germ cell neoplasia unclassified to seminoma. This result provides a rationale whereby androgenic environmental compounds could contribute to increases in TGCT incidence, and identifies for the first time a potential biological pathway influencing whether TGCTs achieve seminomatous versus nonseminomatous histology, a clinically and biologically important distinction.

  7. Quantitative analysis of cone photoreceptor distribution and its relationship with axial length, age, and early age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Ryo Obata

    Full Text Available PURPOSE: It has not been clarified whether early age-related macular degeneration (AMD is associated with cone photoreceptor distribution. We used adaptive optics fundus camera to examine cone photoreceptors in the macular area of aged patients and quantitatively analyzed its relationship between the presence of early AMD and cone distribution. METHODS: Sixty cases aged 50 or older were studied. The eyes were examined with funduscopy and spectral-domain optical coherence tomography to exclude the eyes with any abnormalities at two sites of measurement, 2° superior and 5° temporal to the fovea. High-resolution retinal images with cone photoreceptor mosaic were obtained with adaptive optics fundus camera (rtx1, Imagine Eyes, France. After adjusting for axial length, cone packing density was calculated and the relationship with age, axial length, or severity of early AMD based on the age-related eye disease study (AREDS classification was analyzed. RESULTS: Patient's age ranged from 50 to 77, and axial length from 21.7 to 27.5 mm. Mean density in metric units and that in angular units were 24,900 cells/mm2, 2,170 cells/deg2 at 2° superior, and 18,500 cells/mm2, 1,570 cels/deg2 at 5° temporal, respectively. Axial length was significantly correlated with the density calculated in metric units, but not with that in angular units. Age was significantly correlated with the density both in metric and angular units at 2° superior. There was no significant difference in the density in metric and angular units between the eyes with AREDS category one and those with categories two or three. CONCLUSION: Axial length and age were significantly correlated with parafoveal cone photoreceptor distribution. The results do not support that early AMD might influence cone photoreceptor density in the area without drusen or pigment abnormalities.

  8. Nasalance scores for normal Korean-speaking adults and children: Effects of age, vowel context, and stimulus length.

    Science.gov (United States)

    Ha, Seunghee; Cho, Seong-Hyeon

    2015-08-01

    The purpose of this study was to collect nasalance scores for normal Korean-speaking children and adults and to determine whether age, vowel contexts, and stimulus length influence nasalance scores. Fifty-seven children aged 4-6 years and 17 adults participated in the study. Mean nasalance scores were obtained for eight sentences devoid of nasal consonants divided into the vowel/a/and/i/contexts; the sentences consisted of 4, 8, 16, and 31 syllables. All subjects were asked to repeat the speech stimuli twice after the examiner. The headset of the nasometer was replaced between the first and second recordings. An average value of the nasalance scores from the two recordings for each stimulus was calculated and used in the statistical analysis as a representative measure for each subject. Mean and standard deviations of nasalance scores were obtained for each speech stimulus and each age group. The statistical analysis indicated significant effects of age and vowel context and a significant interaction between age and the vowel context on nasalance scores. However, the effect of stimulus length on nasalance scores was not significant. All speakers had higher nasalance scores for the vowel/i/contexts than for the vowel/a/contexts. Adults had higher nasalance scores compared to children in both vowel contexts. These normal nasalance values from Korean-speaking children aged 4-6 years will provide important reference information for resonance assessment of children with cleft palate who have been considered for secondary palatal surgery. The results of the study suggest that subjects' age and the vowel content of speech stimuli should be carefully considered when interpreting the nasalance scores. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Repeat retail clinic visits: impact of insurance coverage and age of patient.

    Science.gov (United States)

    Angstman, Kurt B; Bernard, Matthew E; Rohrer, James E; Garrison, Gregory M; Maclaughlin, Kathy L

    2012-12-01

    As retail clinics provide a less costly alternative for health care, it would be reasonable to expect an increase in multiple (repeat) retail visits by those patients who may have expenses for receiving primary care. If costs were not a significant factor, then repeat visits should not be significantly different between these patients and those with coverage for primary care visits. The hypothesis for this study was that patients with the potential for out-of-pocket expenses would have a higher frequency of repeat retail clinic visits within 180 days compared to those with primary care coverage. A retrospective chart review was conducted of 5703 patients utilizing a retail clinic in Rochester, Minnesota from January 1, 2009 through June 30, 2009. The first visit to the retail clinic was considered the index visit and the chart was reviewed for repeat retail clinic visits within the next 180 days. Using a multiple logistic regression model, the odds of a pediatric patient (N=2344) having a repeat retail visit within 180 days of the index visit were not significantly impacted by insurance coverage (P=0.4209). Of the 3359 adult patients, those with unknown coverage had a 25.6% higher odds ratio of repeat retail clinic visits than those with insurance coverage (odds ratio 1.2557, confidence interval 1.0421-1.5131). This study suggested that when cost is an issue, the adult patient may favor retail clinics for episodic, low-acuity health care. In contrast, the pediatric population did not, suggesting that other factors, such as convenience, may play more of a role in the choice of episodic health care for this age group.

  10. Active aging as a way of keeping diseases at arm’s length

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    -care, by paying attention to the signals of the body and leading healthy lives (Rose 2001). However, active aging seems to contain an ambiguity in this aspect, as the practice of active aging is often a way for elderly to keep diseases at arm’s length, and not a way to sense the possible abnormalities in the body....... Through ethnographic fieldwork at two activity centres, the author has studied the role of activity and practice of active aging in the everyday live of the elderly users of the centres. There seems to be a fundamental difference between how active aging is thought of at policy level – as a part...

  11. Prognostic significance of telomeric repeat length alterations in pathological stage I-IIIA non-small cell lung cancer.

    Science.gov (United States)

    Hirashima, T; Komiya, T; Nitta, T; Takada, Y; Kobayashi, M; Masuda, N; Matui, K; Takada, M; Kikui, M; Yasumitu, T; Ohno, A; Nakagawa, K; Fukuoka, M; Kawase, I

    2000-01-01

    This study was performed to evaluate the prognostic significance of alteration in telomere length in pathological stage (p-stage) I-IIIA non-small cell lung cancer (NSCLC). Paired cancer and normal lung tissues were obtained from 72 patients with histologically confirmed p-stage I-IIIA NSCLC. Terminal restriction fragment (TRF) length, which indicates telomere length, was measured by Southern blot analysis. Tumor telomerase activity was also assayed by non-radioactive PCR-ELISA in 55 patients. TRF length (mean +/- SD) in normal tissue was 6.2 +/- 1.1 Kb. Therefore, upper and lower limits of normal range in TRF length was set at 8.4 (mean + 2SD) Kb and 4.0 (mean-2SD) Kb, respectively. A tumor showing TRF length over normal range was defined as positive for the alteration. In 72 patients, 25 (34.7%) with alteration in TRF length had significantly shorter survival durations than those of the others. Telomerase activity did not correlate with survival duration. In multivariate analysis, alteration in TRF length (P = 0.0033) was second to p-stage (P = 0.0004) in importance among the various parameters.

  12. Decreasing initial telomere length in humans intergenerationally understates age-associated telomere shortening.

    Science.gov (United States)

    Holohan, Brody; De Meyer, Tim; Batten, Kimberly; Mangino, Massimo; Hunt, Steven C; Bekaert, Sofie; De Buyzere, Marc L; Rietzschel, Ernst R; Spector, Tim D; Wright, Woodring E; Shay, Jerry W

    2015-08-01

    Telomere length shortens with aging, and short telomeres have been linked to a wide variety of pathologies. Previous studies suggested a discrepancy in age-associated telomere shortening rate estimated by cross-sectional studies versus the rate measured in longitudinal studies, indicating a potential bias in cross-sectional estimates. Intergenerational changes in initial telomere length, such as that predicted by the previously described effect of a father's age at birth of his offspring (FAB), could explain the discrepancy in shortening rate measurements. We evaluated whether changes occur in initial telomere length over multiple generations in three large datasets and identified paternal birth year (PBY) as a variable that reconciles the difference between longitudinal and cross-sectional measurements. We also clarify the association between FAB and offspring telomere length, demonstrating that this effect is substantially larger than reported in the past. These results indicate the presence of a downward secular trend in telomere length at birth over generational time with potential public health implications.

  13. Offspring's Leukocyte Telomere Length, Paternal Age, and Telomere Elongation in Sperm

    DEFF Research Database (Denmark)

    Kimura, Masayuki; Cherkas, Lynn F; Kato, Bernet S;

    2008-01-01

    Leukocyte telomere length (LTL) is a complex genetic trait. It shortens with age and is associated with a host of aging-related disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different...... cohorts. Moreover, we examined the potential cause of the paternal age on offspring's LTL by delineating telomere parameters in sperm donors. We measured LTL by Southern blots in Caucasian men and women (n=3365), aged 18-94 years, from the Offspring of the Framingham Heart Study (Framingham Offspring......), the NHLBI Family Heart Study (NHLBI-Heart), the Longitudinal Study of Aging Danish Twins (Danish Twins), and the UK Adult Twin Registry (UK Twins). Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (50 years) donors. Paternal age...

  14. Telomere length and physical performance at older ages: an individual participant meta-analysis.

    Directory of Open Access Journals (Sweden)

    Michael P Gardner

    Full Text Available Telomeres are involved in cellular ageing and shorten with increasing age. If telomere length is a valuable biomarker of ageing, then telomere shortening should be associated with worse physical performance, an ageing trait, but evidence for such an association is lacking. The purpose of this study was to examine whether change in telomere length is associated with physical performance.Using data from four UK adult cohorts (ages 53-80 years at baseline, we undertook cross-sectional and longitudinal analyses. We analysed each study separately and then used meta-analytic methods to pool the results. Physical performance was measured using walking and chair rise speed, standing balance time and grip strength. Telomere length was measured by quantitative real-time polymerase chain reaction (PCR in whole blood at baseline and follow-up (time 1, time 2.Total sample sizes in meta-analyses ranged from 1,217 to 3,707. There was little evidence that telomere length was associated with walking speed, balance or grip strength, though weak associations were seen with chair rise speed and grip strength at baseline (p = 0.02 and 0.01 respectively. Faster chair rise speed at follow-up, was associated with a smaller decline in telomere length between time 1 and time 2 (standardised coefficient per SD increase 0.061, 95% CI 0.006, 0.115, p = 0.03 but this was consistent with chance (p =0.08 after further adjustment.Whereas shortening of leukocyte telomeres might be an important measure of cellular ageing, there is little evidence that it is a strong biomarker for physical performance.

  15. An all-atom model of the chromatin fiber containing linker histones reveals a versatile structure tuned by the nucleosomal repeat length.

    Directory of Open Access Journals (Sweden)

    Hua Wong

    Full Text Available In the nucleus of eukaryotic cells, histone proteins organize the linear genome into a functional and hierarchical architecture. In this paper, we use the crystal structures of the nucleosome core particle, B-DNA and the globular domain of H5 linker histone to build the first all-atom model of compact chromatin fibers. In this 3D jigsaw puzzle, DNA bending is achieved by solving an inverse kinematics problem. Our model is based on recent electron microscopy measurements of reconstituted fiber dimensions. Strikingly, we find that the chromatin fiber containing linker histones is a polymorphic structure. We show that different fiber conformations are obtained by tuning the linker histone orientation at the nucleosomes entry/exit according to the nucleosomal repeat length. We propose that the observed in vivo quantization of nucleosomal repeat length could reflect nature's ability to use the DNA molecule's helical geometry in order to give chromatin versatile topological and mechanical properties.

  16. Sports and Exercise at Different Ages and Leukocyte Telomere Length in Later Life – Data from the Berlin Aging Study II (BASE-II)

    Science.gov (United States)

    Saßenroth, Denise; Meyer, Antje; Salewsky, Bastian; Kroh, Martin; Norman, Kristina; Steinhagen-Thiessen, Elisabeth; Demuth, Ilja

    2015-01-01

    Physical activity and sports have repeatedly been reported to be associated with telomere length. We studied the association of different types of sports across different stages of life on relative leukocyte telomere length (rLTL) in advanced age.815 participants (397 men) from the Berlin Aging Study II aged over 61 years were included in the analysis. rLTL was measured by real time PCR and physical activity was determined retrospectively by questionnaire, assessing type and duration of sports in the past as well as currently. Five separate multiple linear regression models adjusted for various control variables were performed. 67.3% of participants exercised currently, whereas 19.4% performed sports only between the age of 20 and 30. rLTL was higher in subjects who stated to exercise currently (N = 456), and in subjects who engaged in endurance (N = 138) or intensive activity sports (N = 32). Current physical activity was positively associated with rLTL in the risk factor adjusted regression model (β = 0.26, p < 0.001) and practicing sports for a minimum of 10 years preceding the assessment had a significant effect on rLTL (β = 0.39, p = 0.011). The highest impact was seen for intensive activity sports (β = 0.79, p < 0.001) and physical activity since at least 42 years (β = 0.47, p = 0.001). However, physical activity only between 20 and 30 years of age did not affect rLTL in old age when compared to no sports at all (β = -0.16, p = 0.21). Physical activity is clearly associated with longer rLTL. The effect is seen with longer periods of physical activity (at least 10 years), with intensive sports activities having the greatest impact on rLTL. Our data suggest that regular physical activity for at least 10 years is necessary to achieve a sustained effect on rLTL. PMID:26630493

  17. Sports and Exercise at Different Ages and Leukocyte Telomere Length in Later Life--Data from the Berlin Aging Study II (BASE-II.

    Directory of Open Access Journals (Sweden)

    Denise Saßenroth

    Full Text Available Physical activity and sports have repeatedly been reported to be associated with telomere length. We studied the association of different types of sports across different stages of life on relative leukocyte telomere length (rLTL in advanced age.815 participants (397 men from the Berlin Aging Study II aged over 61 years were included in the analysis. rLTL was measured by real time PCR and physical activity was determined retrospectively by questionnaire, assessing type and duration of sports in the past as well as currently. Five separate multiple linear regression models adjusted for various control variables were performed. 67.3% of participants exercised currently, whereas 19.4% performed sports only between the age of 20 and 30. rLTL was higher in subjects who stated to exercise currently (N = 456, and in subjects who engaged in endurance (N = 138 or intensive activity sports (N = 32. Current physical activity was positively associated with rLTL in the risk factor adjusted regression model (β = 0.26, p < 0.001 and practicing sports for a minimum of 10 years preceding the assessment had a significant effect on rLTL (β = 0.39, p = 0.011. The highest impact was seen for intensive activity sports (β = 0.79, p < 0.001 and physical activity since at least 42 years (β = 0.47, p = 0.001. However, physical activity only between 20 and 30 years of age did not affect rLTL in old age when compared to no sports at all (β = -0.16, p = 0.21. Physical activity is clearly associated with longer rLTL. The effect is seen with longer periods of physical activity (at least 10 years, with intensive sports activities having the greatest impact on rLTL. Our data suggest that regular physical activity for at least 10 years is necessary to achieve a sustained effect on rLTL.

  18. Respiratory failure in a mouse model of myotonic dystrophy does not correlate with the CTG repeat length.

    OpenAIRE

    Panaite, P.A.; Kuntzer, T; Gourdon, G; Barakat-Walter, I.

    2013-01-01

    Myotonic dystrophy (DM1) is a multisystemic disease caused by an expansion of CTG repeats in the region of DMPK, the gene encoding DM protein kinase. The severity of muscle disability in DM1 correlates with the size of CTG expansion. As respiratory failure is one of the main causes of death in DM1, we investigated the correlation between respiratory impairment and size of the (CTG)n repeat in DM1 animal models. Using pressure plethysmography the respiratory function was assessed in control an...

  19. Greater length-for-age increases the odds of attaining motor milestones in Vietnamese children aged 5-18 months.

    Science.gov (United States)

    Kulkarni, Shibani; Ramakrishnan, Usha; Dearden, Kirk A; Marsh, David R; Ha, Tran Thu; Tran, Thach Duc; Pachón, Helena

    2012-01-01

    Early childhood malnutrition has been associated with delayed development. Limited data exist however about the timing of developmental delay early in life. We assessed motor milestone (MM) achievement using the World Health Organization's windows of achievement for gross motor milestones. We performed secondary analysis of baseline data of 158 Vietnamese children aged 5-18 months from a randomized community intervention trial. Median age of motor milestone achievement was compared to WHO reported medians. Multivariate logistic regression was used to identify socioeconomic, anthropometric and dietary factors associated with motor milestone achievement during the windows of achievement. Thirty four per cent of the children were stunted. Median age of MM achievement of Vietnamese children lagged by 2.4-3.7 months, compared to the WHO median for all MMs. Greater length-for-age increased the odds for walking with assistance, standing alone and walking alone by more than 3 times. Greater weight-for-age increased the odds by 3.6 for hand-and-knees crawling. Likewise, frequency of daily complementary feeding raised the odds by 3.6 for standing with assistance. In this first application of WHO windows of achievement in Viet Nam, pre-schoolers achieved motor milestones later than WHO reported median age. High prevalence of stunting and association of length-for-age with motor milestone achievement underscore the importance of addressing chronic malnutrition to optimize children's growth and development.

  20. Hexanucleotide repeats in ALS/FTD form length-dependent RNA foci, sequester RNA binding proteins, and are neurotoxic.

    Science.gov (United States)

    Lee, Youn-Bok; Chen, Han-Jou; Peres, João N; Gomez-Deza, Jorge; Attig, Jan; Stalekar, Maja; Troakes, Claire; Nishimura, Agnes L; Scotter, Emma L; Vance, Caroline; Adachi, Yoshitsugu; Sardone, Valentina; Miller, Jack W; Smith, Bradley N; Gallo, Jean-Marc; Ule, Jernej; Hirth, Frank; Rogelj, Boris; Houart, Corinne; Shaw, Christopher E

    2013-12-12

    The GGGGCC (G4C2) intronic repeat expansion within C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Intranuclear neuronal RNA foci have been observed in ALS and FTD tissues, suggesting that G4C2 RNA may be toxic. Here, we demonstrate that the expression of 38× and 72× G4C2 repeats form intranuclear RNA foci that initiate apoptotic cell death in neuronal cell lines and zebrafish embryos. The foci colocalize with a subset of RNA binding proteins, including SF2, SC35, and hnRNP-H in transfected cells. Only hnRNP-H binds directly to G4C2 repeats following RNA immunoprecipitation, and only hnRNP-H colocalizes with 70% of G4C2 RNA foci detected in C9ORF72 mutant ALS and FTD brain tissues. We show that expanded G4C2 repeats are potently neurotoxic and bind hnRNP-H and other RNA binding proteins. We propose that RNA toxicity and protein sequestration may disrupt RNA processing and contribute to neurodegeneration.

  1. Parameterization of European perch Perca fluviatilis length-at-age data using stochastic Gompertz growth models.

    Science.gov (United States)

    Troynikov, V S; Gorfine, H K; Ložys, L; Pūtys, Z; Jakubavičiūtė, E; Day, R W

    2011-12-01

    Three stochastic versions of the Gompertz growth model were used to parameterize total length (L(T) )-at-age data for perch Perca fluviatilis, an important target species for commercial and recreational fishers and a food species for predatory fishes and aquatic birds. Each model addresses growth heterogeneity by incorporating random parameters from a specific positive distribution: Weibull, gamma or log-normal. The modelling outputs for each version of the model provide L(T) distributions for selected ages and percentiles of L(T) at age for both males and females. The results highlight the importance of using a stochastic approach and the logistic-like growth pattern for analysing growth data for P. fluviatilis in Curonian Lagoon (Lithuania). Outputs from this modelling can be extended to a stochastic analysis of fish cohort dynamics, incorporating all length-based biological relationships, and the selectivity-related interactions between fish cohorts and fishing gear.

  2. Telomere length in subjects with schizophrenia, their unaffected siblings and healthy controls: Evidence of accelerated aging.

    Science.gov (United States)

    Czepielewski, Leticia Sanguinetti; Massuda, Raffael; Panizzutti, Bruna; da Rosa, Eduarda Dias; de Lucena, David; Macêdo, Danielle; Grun, Lucas Kich; Barbé-Tuana, Florencia María; Gama, Clarissa Severino

    2016-07-01

    Schizophrenia (SZ) is associated with broad burden. The clinical manifestations of SZ are related to pathophysiological alterations similar to what is seen in normal aging. Our aim was to evaluate the differences in telomere length (TL), a biomarker of cellular aging, in subjects with SZ (n=36), unaffected siblings (SB, n=36) and healthy controls (HC, n=47). SZ had shorter TL compared to HC, but no difference was found in SB comparing to SZ. These findings indicate that a pathological accelerated aging profile could be present in the course of SZ and further studies are needed to confirm TL as potential endophenotype, especially in at risk populations.

  3. The Effect of Gestational Age on Axial Length of the Eyes of Premature Infants

    Directory of Open Access Journals (Sweden)

    Mehmet Ali Sekeroglu

    2016-01-01

    Full Text Available Aim: The aim of the present study is to evaluate the axial length of the eyes of premature infants without retinopathy of prematurity and to document the relationship with gestational age and changes as infants grew-up. Material and Method: The axial length of the eyes were measured by using a mobile A-scan ultrasonographic biometry device just before the first retinopathy of prematurity screening examination and 4-weeks thereafter. Results: One-hundred and thirty-six infants with a mean gestational age of 31,7±2,7 weeks and a birth-weight of 1561.0±379.3 g were included in the study. Axial length measurements were done at a mean postconceptional age of 35.8 ±2.6 (31-40 and 39.8±2.7 (35-44 weeks, consecutively. The mean axial length at first and second visits were 16.43±0.42 mm (15.28-17.13 and 16.69±0.41 mm (15.60-17.70, consecutively (p

  4. Mitochondrial Inverted Repeats Strongly Correlate with Lifespan: mtDNA Inversions and Aging

    Science.gov (United States)

    Yang, Jiang-Nan; Seluanov, Andrei; Gorbunova, Vera

    2013-01-01

    Mitochondrial defects are implicated in aging and in a multitude of age-related diseases, such as cancer, heart failure, Parkinson’s disease, and Huntington’s disease. However, it is still unclear how mitochondrial defects arise under normal physiological conditions. Mitochondrial DNA (mtDNA) deletions caused by direct repeats (DRs) are implicated in the formation of mitochondrial defects, however, mitochondrial DRs show relatively weak (Pearson’s r = −0.22, p<0.002; Spearman’s ρ = −0.12, p = 0.1) correlation with maximum lifespan (MLS). Here we report a stronger correlation (Pearson’s r = −0.55, p<10–16; Spearman’s ρ = −0.52, p<10–14) between mitochondrial inverted repeats (IRs) and lifespan across 202 species of mammals. We show that, in wild type mice under normal conditions, IRs cause inversions, which arise by replication-dependent mechanism. The inversions accumulate with age in the brain and heart. Our data suggest that IR-mediated inversions are more mutagenic than DR-mediated deletions in mtDNA, and impose stronger constraint on lifespan. Our study identifies IR-induced mitochondrial genome instability during mtDNA replication as a potential cause for mitochondrial defects. PMID:24069185

  5. Mitochondrial inverted repeats strongly correlate with lifespan: mtDNA inversions and aging.

    Directory of Open Access Journals (Sweden)

    Jiang-Nan Yang

    Full Text Available Mitochondrial defects are implicated in aging and in a multitude of age-related diseases, such as cancer, heart failure, Parkinson's disease, and Huntington's disease. However, it is still unclear how mitochondrial defects arise under normal physiological conditions. Mitochondrial DNA (mtDNA deletions caused by direct repeats (DRs are implicated in the formation of mitochondrial defects, however, mitochondrial DRs show relatively weak (Pearson's r = -0.22, p<0.002; Spearman's ρ = -0.12, p = 0.1 correlation with maximum lifespan (MLS. Here we report a stronger correlation (Pearson's r = -0.55, p<10(-16; Spearman's ρ = -0.52, p<10(-14 between mitochondrial inverted repeats (IRs and lifespan across 202 species of mammals. We show that, in wild type mice under normal conditions, IRs cause inversions, which arise by replication-dependent mechanism. The inversions accumulate with age in the brain and heart. Our data suggest that IR-mediated inversions are more mutagenic than DR-mediated deletions in mtDNA, and impose stronger constraint on lifespan. Our study identifies IR-induced mitochondrial genome instability during mtDNA replication as a potential cause for mitochondrial defects.

  6. Metabolic rate variation over adult lifetime in the butterfly Vanessa cardui (Nymphalidae: Nymphalinae): aging, feeding, and repeatability.

    Science.gov (United States)

    Woods, William A; Wood, C A L; Ebersole, John; Stevenson, R D

    2010-01-01

    Questions about the adaptive importance of metabolic rate can be approached only when measurements of differences between individuals are repeatable. We made daily measurements of CO(2) production, body mass, and food uptake over the adult life span of unmated Vanessa cardui kept under constant environmental conditions in both fed and unfed treatments. Mass and CO(2) production generally declined with age in both treatments, though with much day-to-day variability in the fed treatment. For the full samples, metabolic rate was repeatable for the unfed treatment (repeatability r = 0.60) but not for the fed treatment (r = 0.03). Differences between fed and unfed individuals of the same age range were repeatable for the unfed treatment (r = 0.39) but not for the fed treatment (r = -0.20). Removing age effects on CO(2) production yielded still higher repeatability in the unfed treatment (r = 0.83), though not in fed butterflies of the same age range (r = -0.02). However, repeatability of CO(2) production of fed butterflies increased sharply with age, rising to 0.82 for butterflies age 8-10 d. Although food uptake mass was repeatable (r = 0.52), feeding history explained little variation in CO(2) production. We conclude that for V. cardui and possibly for other insects of similar feeding habit, variation in metabolic rate between individuals is best represented by measurements of unfed individuals of the same age or of older fed individuals.

  7. Aging is not a barrier to muscle and redox adaptations: applying the repeated eccentric exercise model.

    Science.gov (United States)

    Nikolaidis, Michalis G; Kyparos, Antonios; Spanou, Chrysa; Paschalis, Vassilis; Theodorou, Anastasios A; Panayiotou, George; Grivas, Gerasimos V; Zafeiridis, Andreas; Dipla, Konstantina; Vrabas, Ioannis S

    2013-08-01

    Despite the progress of analytic techniques and the refinement of study designs, striking disagreement exists among studies regarding the influence of exercise on muscle function and redox homeostasis in the elderly. The repeated eccentric exercise model was applied to produce long-lasting and extensive changes in redox biomarkers and to reveal more effectively the potential effects of aging on redox homeostasis. Ten young (20.6±0.5 years) and ten elderly men (64.6±1.1 years) underwent an isokinetic eccentric exercise session, which was repeated after three weeks. Muscle function/damage indices (torque, range of movement, muscle soreness and creatine kinase) and redox biomarkers (F2-isoprostanes, protein carbonyls, glutathione, catalase, superoxide dismutase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, uric acid, bilirubin and albumin) were assessed in plasma, erythrocytes or urine pre-exercise, immediately post-exercise and at 2 and 4 days post-exercise. As expected, the elderly group exhibited oxidative stress in baseline compared to the young group. Extensive muscle damage and extensive alterations in redox homeostasis appeared after the first bout of eccentric exercise. Noteworthy, the redox responses were similar between the age groups despite their differences in baseline values. Likewise, both age groups demonstrated blunted alterations in muscle damage and redox homeostasis after the second bout of eccentric exercise indicating adaptations from the first bout of exercise. Elderly individuals seem to be well fitted to participate in demanding physical activities without suffering detrimental effects on skeletal muscle and/or disturbances on redox homeostasis. The repeated eccentric exercise model may be a useful and practical physiological tool to study redox biology in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Estimating age from recapture data: integrating incremental growth measures with ancillary data to infer age-at-length

    Science.gov (United States)

    Eaton, Mitchell J.; Link, William A.

    2011-01-01

    Estimating the age of individuals in wild populations can be of fundamental importance for answering ecological questions, modeling population demographics, and managing exploited or threatened species. Significant effort has been devoted to determining age through the use of growth annuli, secondary physical characteristics related to age, and growth models. Many species, however, either do not exhibit physical characteristics useful for independent age validation or are too rare to justify sacrificing a large number of individuals to establish the relationship between size and age. Length-at-age models are well represented in the fisheries and other wildlife management literature. Many of these models overlook variation in growth rates of individuals and consider growth parameters as population parameters. More recent models have taken advantage of hierarchical structuring of parameters and Bayesian inference methods to allow for variation among individuals as functions of environmental covariates or individual-specific random effects. Here, we describe hierarchical models in which growth curves vary as individual-specific stochastic processes, and we show how these models can be fit using capture–recapture data for animals of unknown age along with data for animals of known age. We combine these independent data sources in a Bayesian analysis, distinguishing natural variation (among and within individuals) from measurement error. We illustrate using data for African dwarf crocodiles, comparing von Bertalanffy and logistic growth models. The analysis provides the means of predicting crocodile age, given a single measurement of head length. The von Bertalanffy was much better supported than the logistic growth model and predicted that dwarf crocodiles grow from 19.4 cm total length at birth to 32.9 cm in the first year and 45.3 cm by the end of their second year. Based on the minimum size of females observed with hatchlings, reproductive maturity was estimated

  9. Canine length in wild male baboons: maturation, aging and social dominance rank.

    Science.gov (United States)

    Galbany, Jordi; Tung, Jenny; Altmann, Jeanne; Alberts, Susan C

    2015-01-01

    Canines represent an essential component of the dentition for any heterodont mammal. In primates, like many other mammals, canines are frequently used as weapons. Hence, tooth size and wear may have significant implications for fighting ability, and consequently for social dominance rank, reproductive success, and fitness. We evaluated sources of variance in canine growth and length in a well-studied wild primate population because of the potential importance of canines for male reproductive success in many primates. Specifically, we measured maxillary canine length in 80 wild male baboons (aged 5.04-20.45 years) from the Amboseli ecosystem in southern Kenya, and examined its relationship with maturation, age, and social dominance rank. In our analysis of maturation, we compared food-enhanced baboons (those that fed part time at a refuse pit associated with a tourist lodge) with wild-feeding males, and found that food-enhanced males achieved long canines earlier than wild-feeding males. Among adult males, canine length decreased with age because of tooth wear. We found some evidence that, after controlling for age, longer canines were associated with higher adult dominance rank (accounting for 9% of the variance in rank), but only among relatively high-ranking males. This result supports the idea that social rank, and thus reproductive success and fitness, may depend in part on fighting ability mediated by canine size.

  10. Canine length in wild male baboons: maturation, aging and social dominance rank.

    Directory of Open Access Journals (Sweden)

    Jordi Galbany

    Full Text Available Canines represent an essential component of the dentition for any heterodont mammal. In primates, like many other mammals, canines are frequently used as weapons. Hence, tooth size and wear may have significant implications for fighting ability, and consequently for social dominance rank, reproductive success, and fitness. We evaluated sources of variance in canine growth and length in a well-studied wild primate population because of the potential importance of canines for male reproductive success in many primates. Specifically, we measured maxillary canine length in 80 wild male baboons (aged 5.04-20.45 years from the Amboseli ecosystem in southern Kenya, and examined its relationship with maturation, age, and social dominance rank. In our analysis of maturation, we compared food-enhanced baboons (those that fed part time at a refuse pit associated with a tourist lodge with wild-feeding males, and found that food-enhanced males achieved long canines earlier than wild-feeding males. Among adult males, canine length decreased with age because of tooth wear. We found some evidence that, after controlling for age, longer canines were associated with higher adult dominance rank (accounting for 9% of the variance in rank, but only among relatively high-ranking males. This result supports the idea that social rank, and thus reproductive success and fitness, may depend in part on fighting ability mediated by canine size.

  11. Respiratory failure in a mouse model of myotonic dystrophy does not correlate with the CTG repeat length.

    Science.gov (United States)

    Panaite, Petrica-Adrian; Kuntzer, Thierry; Gourdon, Geneviève; Barakat-Walter, Ibtissam

    2013-10-01

    Myotonic dystrophy (DM1) is a multisystemic disease caused by an expansion of CTG repeats in the region of DMPK, the gene encoding DM protein kinase. The severity of muscle disability in DM1 correlates with the size of CTG expansion. As respiratory failure is one of the main causes of death in DM1, we investigated the correlation between respiratory impairment and size of the (CTG)n repeat in DM1 animal models. Using pressure plethysmography the respiratory function was assessed in control and transgenic mice carrying either 600 (DM600) or >1300 CTG repeats (DMSXL). The statistical analysis of respiratory parameters revealed that both DM1 transgenic mice sub-lines show respiratory impairment compared to control mice. In addition, there is no significant difference in breathing functions between the DM600 and DMSXL mice. In conclusion, these results indicate that respiratory impairment is present in both transgenic mice sub-lines, but the severity of respiratory failure is not related to the size of the (CTG)n expansion.

  12. Three-dimensional anatomy of equine incisors: tooth length, enamel cover and age related changes.

    Science.gov (United States)

    Schrock, Patricia; Lüpke, Matthias; Seifert, Hermann; Staszyk, Carsten

    2013-12-09

    Equine incisors are subjected to continuous occlusal wear causing multiple, age related changes of the extragingival crown. It is assumed that the occlusal wear is compensated by continued tooth elongation at the apical ends of the teeth. In this study, μCT-datasets offered the opportunity to analyze the three-dimensional appearance of the extra- and intraalveolar parts of the enamel containing dental crown as well as of the enamel-free dental root. Multiple morphometric measurements elucidated age related, morphological changes within the intraalveolar part of the incisors. Equine incisors possess a unique enamel cover displaying large indentations on the mesial and distal sides. After eruption tooth elongation at the apical end outbalances occlusal wear for two to four years resulting in increasing incisor length in this period of time. Remarkably, this maximum length is maintained for about ten years, up to a tooth age of 13 to 15 years post eruption. Variances in the total length of individual teeth are related to different Triadan positions (central-, middle- and corner incisors) as well as to the upper and lower arcades. Equine incisors are able to fully compensate occlusal wear for a limited period of time. However, after this ability ceases, it is expected that a diminished intraalveolar tooth length will cause massive changes in periodontal biomechanics. The time point of these morphodynamic and biomechanical changes (13 to 15 years post eruption) occurs in coincidence with the onset of a recently described destructive disease of equine incisor (equine odontoclastic tooth resorption and hypercementosis) in aged horses. However, further biomechanical, cell biological and microbiological investigations are needed to elucidate a correlation between age related changes of incisor morphology and this disease.

  13. Offspring's leukocyte telomere length, paternal age, and telomere elongation in sperm.

    Directory of Open Access Journals (Sweden)

    Masayuki Kimura

    2008-02-01

    Full Text Available Leukocyte telomere length (LTL is a complex genetic trait. It shortens with age and is associated with a host of aging-related disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different cohorts. Moreover, we examined the potential cause of the paternal age on offspring's LTL by delineating telomere parameters in sperm donors. We measured LTL by Southern blots in Caucasian men and women (n=3365, aged 18-94 years, from the Offspring of the Framingham Heart Study (Framingham Offspring, the NHLBI Family Heart Study (NHLBI-Heart, the Longitudinal Study of Aging Danish Twins (Danish Twins, and the UK Adult Twin Registry (UK Twins. Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (50 years donors. Paternal age had an independent effect, expressed by a longer LTL in males of the Framingham Offspring and Danish Twins, males and females of the NHLBI-Heart, and females of UK Twins. For every additional year of paternal age, LTL in offspring increased at a magnitude ranging from half to more than twice of the annual attrition in LTL with age. Moreover, sperm telomere length analyses were compatible with the emergence in older men of a subset of sperm with elongated telomeres. Paternal age exerts a considerable effect on the offspring's LTL, a phenomenon which might relate to telomere elongation in sperm from older men. The implications of this effect deserve detailed study.

  14. Repeatability of contrast sensitivity testing in patients with age-related macular degeneration, glaucoma, and cataract

    Directory of Open Access Journals (Sweden)

    Selcuk Kara

    Full Text Available ABSTRACT Purpose: To analyze the intrasession and intersession repeatability of contrast sensitivity (CS measurements in patients with glaucoma, cataract, or age-related macular degeneration (AMD and healthy controls. Methods: CS measurements were performed using the OPTEC-Functional Vision Analyzer (FVA, which uses a standardized and closed (view-in system. Measurements for patients with glaucoma, cataract, or AMD and healthy controls were repeated within 30 minutes (intrasession and during two sessions (intersession, separated by one week to one month. Test-retest reliability and correlation were measured using the intraclass correlation coefficient (ICC and coefficient of repeatability (COR. Results: Ninety subjects (90 eyes with visual acuity of 0.17 logMAR or higher in the cataract group or 0.00 logMAR in the other groups were included. During the first session, the ICC values were 0.87, 0.90, 0.76, and 0.69, and COR values were 0.24, 0.20, 0.38, and 0.25 for the control, glaucoma, cataract, and AMD groups, respectively. The reliability scores significantly improved during the second session, except in the glaucoma group. There was an acceptable floor effect and no ceiling effect at higher frequencies in the glaucoma and AMD groups. Conclusion: In subjects with good visual acuity, the FVA system is useful for evaluating CS and demonstrates good repeatability, as shown by ICC and COR. Because there is no ceiling effect, this system is beneficial for evaluation of early changes in CS, particularly in patients with glaucoma or AMD.

  15. Relationship among Repeated Sprint Ability, Chronological Age and Puberty in young soccer players.

    Science.gov (United States)

    Perroni, Fabrizio; Pintus, Antonio; Frandino, Mattia; Guidetti, Laura; Baldari, Carlo

    2016-01-20

    The aim of this study was to analyzed the relationship of Repeated Sprinting Ability (RSA) with chronological age and puberty in 100 young soccer players (Age: 13 ± 3 yr - 160 ± 33 month-; High: 159 ± 16 cm, Weight: 49.7 ± 14.1 kg; BMI 19.2 ± 2.5 kg/m) grouped on "Pulcini" (9 - 10 yrs), "Esordienti" (11 - 12 yrs), "Giovanissimi" (13 - 14 yrs), "Allievi" (15 - 16 yrs) and "Juniores" (> 17 yrs) categories. Anthropometric (Weight, Height, BMI), RSA (7x30 m sprint with 25s active rest: Total Time -TT, the lowest sprinting time (LST) and the fatigue index percentage -%IF), and Development (Self-Administered Rating Scale for pubertal development - PDS; Puberty) parameters were measured. ANOVA among categories was applied to asses differences (pinjury and overtraining during the different phases of growth and maturation.

  16. Infant bone age estimation based on fibular shaft length: model development and clinical validation

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Andy; Stamoulis, Catherine; Bixby, Sarah D.; Breen, Micheal A.; Connolly, Susan A.; Kleinman, Paul K. [Boston Children' s Hospital, Harvard Medical School, Department of Radiology, Boston, MA (United States)

    2016-03-15

    Bone age in infants (<1 year old) is generally estimated using hand/wrist or knee radiographs, or by counting ossification centers. The accuracy and reproducibility of these techniques are largely unknown. To develop and validate an infant bone age estimation technique using fibular shaft length and compare it to conventional methods. We retrospectively reviewed negative skeletal surveys of 247 term-born low-risk-of-abuse infants (no persistent child protection team concerns) from July 2005 to February 2013, and randomized them into two datasets: (1) model development (n = 123) and (2) model testing (n = 124). Three pediatric radiologists measured all fibular shaft lengths. An ordinary linear regression model was fitted to dataset 1, and the model was evaluated using dataset 2. Readers also estimated infant bone ages in dataset 2 using (1) the hemiskeleton method of Sontag, (2) the hemiskeleton method of Elgenmark, (3) the hand/wrist atlas of Greulich and Pyle, and (4) the knee atlas of Pyle and Hoerr. For validation, we selected lower-extremity radiographs of 114 normal infants with no suspicion of abuse. Readers measured the fibulas and also estimated bone ages using the knee atlas. Bone age estimates from the proposed method were compared to the other methods. The proposed method outperformed all other methods in accuracy and reproducibility. Its accuracy was similar for the testing and validating datasets, with root-mean-square error of 36 days and 37 days; mean absolute error of 28 days and 31 days; and error variability of 22 days and 20 days, respectively. This study provides strong support for an infant bone age estimation technique based on fibular shaft length as a more accurate alternative to conventional methods. (orig.)

  17. Androgen receptor gene methylation and exon one CAG repeat length in ovarian cancer: differences from breast cancer.

    Science.gov (United States)

    Kassim, Samar; Zoheiry, Nivan M; Hamed, Wael M; Going, James J; Craft, John A

    2004-07-01

    More than one neoplastic founder clone can exist in benign epithelial tumours. Although theories of clonal selection make pluriclonality appear unlikely in carcinomas, published data do not exclude this possibility. This study looked for evidence of multiclonal X inactivation in ovarian carcinoma using AR methylation as a marker. Fifteen unifocal ovarian carcinomas and 14 multifocal carcinomas all in Scottish patients were studied. One representative formalin-fixed paraffin-embedded tumour block was chosen for each of the former and two for the latter. From each of these 43 tumour blocks three samples each of approximately 10(4) carcinoma cells were obtained by microdissection (129 in all). DNA released by proteinase K digestion was subjected to PCR amplification of the androgen receptor gene AR exon I CAG repeat polymorphism with and without prior digestion with methylation-sensitive restriction enzymes HpaII and HhaI. Complex amplification patterns were consistent with mosaic X inactivation in some ovarian carcinomas but acquired anomalies of AR methylation cannot be excluded. Parallel analysis of other X-linked polymorphic loci would strengthen the inference of clonality status from DNA methylation data in tumour X studies. Strikingly, the number of CAG repeats in the 29 ovarian tumour patients (median 16, range 11 - 20) was substantially fewer than in 34 previously studied breast cancer patients from the same scottish population (median 21, range 14 - 26; P CAG repeat were over-represented in the ovarian cancer patients but not in the breast cancer series. These findings reinforce recent suggestions that AR may have a role in ovarian carcinogenesis.

  18. Repeated modification of early limb morphogenesis programmes underlies the convergence of relative limb length in Anolis lizards

    OpenAIRE

    Sanger, Thomas J.; Revell, Liam J.; Gibson-Brown, Jeremy J.; Losos, Jonathan B

    2011-01-01

    The independent evolution of similar morphologies has long been a subject of considerable interest to biologists. Does phenotypic convergence reflect the primacy of natural selection, or does development set the course of evolution by channelling variation in certain directions? Here, we examine the ontogenetic origins of relative limb length variation among Anolis lizard habitat specialists to address whether convergent phenotypes have arisen through convergent developmental trajectories. De...

  19. The number of CAG repeats within the normal allele does not influence the age of onset in Huntington's disease.

    Science.gov (United States)

    Klempíř, Jiří; Zidovská, Jana; Stochl, Jan; Ing, Věra Kebrdlová; Uhrová, Tereza; Roth, Jan

    2011-01-01

    Huntington's disease (HD) is caused by the expansion of the number of CAG repeats on the chromosome 4p16.3, which results in elongated glutamine tract of huntingtin. The purpose of this work was to examine the interaction between the normal and mutant alleles of this gene and their effect on the clinical onset of HD. We hypothesized that in patients with identical number of CAG repeats within the mutant allele, the age of onset of HD is influenced by the number of CAG repeats within the normal allele. We analyzed the relations between the number of CAG repeats within the normal and mutant alleles, the age at HD onset, and the character of initial symptoms in 468 patients with clinically expressed HD. Although the Cox regression coefficient of 0.15 was significant (P CAG repeats within normal allele. Within the groups of patients with the same number of CAG repeats of the mutant allele, number of CAG repeats of the normal allele was found uncorrelated to the age at onset. Furthermore, when analyzing subgroups of patients with the same allelic composition on both alleles, we failed to observe any correlation with the age at the onset. Our analysis gives no corroboration to the idea of a normal allele having a share in the modification of the age at HD onset. We believe that with the current state of knowledge it is not possible to devise a mathematical model for HD onset prediction because too many entirely unknown modifying factors are still involved.

  20. Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians.

    Science.gov (United States)

    Arai, Yasumichi; Martin-Ruiz, Carmen M; Takayama, Michiyo; Abe, Yukiko; Takebayashi, Toru; Koyasu, Shigeo; Suematsu, Makoto; Hirose, Nobuyoshi; von Zglinicki, Thomas

    2015-10-01

    To determine the most important drivers of successful ageing at extreme old age, we combined community-based prospective cohorts: Tokyo Oldest Old Survey on Total Health (TOOTH), Tokyo Centenarians Study (TCS) and Japanese Semi-Supercentenarians Study (JSS) comprising 1554 individuals including 684 centenarians and (semi-)supercentenarians, 167 pairs of centenarian offspring and spouses, and 536 community-living very old (85 to 99 years). We combined z scores from multiple biomarkers to describe haematopoiesis, inflammation, lipid and glucose metabolism, liver function, renal function, and cellular senescence domains. In Cox proportional hazard models, inflammation predicted all-cause mortality with hazard ratios (95% CI) 1.89 (1.21 to 2.95) and 1.36 (1.05 to 1.78) in the very old and (semi-)supercentenarians, respectively. In linear forward stepwise models, inflammation predicted capability (10.8% variance explained) and cognition (8(.)6% variance explained) in (semi-)supercentenarians better than chronologic age or gender. The inflammation score was also lower in centenarian offspring compared to age-matched controls with Δ (95% CI) = - 0.795 (- 1.436 to - 0.154). Centenarians and their offspring were able to maintain long telomeres, but telomere length was not a predictor of successful ageing in centenarians and semi-supercentenarians. We conclude that inflammation is an important malleable driver of ageing up to extreme old age in humans.

  1. Geographical variation and sexual differences of body length and age composition in Rana temporaria: the ontogenetic development and phenotypic trends

    Directory of Open Access Journals (Sweden)

    Lyapkov Sergey

    2012-06-01

    Full Text Available The analysis of literature data on the mean values of age and body length of adult individuals of widespread species Rana temporaria from about 70 spatially separated populations, including our published data, was conducted. The evident trend in population mean age increase with the decrease of the of activity season length was revealed as well as the absence of that trend in the mean body length, with the maximal mean value in body length being near central part of the range. Our explanation of non-linear trend in the mean values of body length does not contradict other models of geographic variability explaining the correspondence and discrepance with the Bergman rule. In addition our explanation corresponds to the revealed features of interpopulation variation in growth rate. The revealed trend of variation in the mean body length is resulted from both growth rate decrease and mean age increase with the decrease in the length of activity season. The relatively low mean values of body length in populations from south and southern-west borders of the range are explained not only by low mean age but by lower growth rate despite high length of activity season. The interpopulation variation in body length is determined not only by body length but by age composition differences both between and within population. Therefore, the direction and intensity of sexual differences have not distinct trends, and the correspondence to Rensch rule (in contrast to Bergman rule is rarely observed.

  2. ATXN2 with intermediate-length CAG/CAA repeats does not seem to be a risk factor in hereditary spastic paraplegia

    DEFF Research Database (Denmark)

    Nielsen, Troels Tolstrup; Svenstrup, Kirsten; Budtz-Jørgensen, Esben

    2012-01-01

    degeneration with motor neuron disease (FTD-MND), since TDP-43 positive inclusions have recently been found in an HSP subtype, and TDP-43 are found in abundance in pathological inclusions of both ALS and FTD-MND. Furthermore, ataxin-2 (encoded by the gene ATXN2), a polyglutamine containing protein elongated...... in spinocerebellar ataxia type 2, has been shown to be a modulator of TDP-43 induced toxicity in ALS animal and cell models. Finally, it has been shown that ATXN2 with non-pathogenic intermediate-length CAG/CAA repeat elongations (encoding the polyglutamine tract) is a genetic risk factor of ALS. Considering...

  3. A novel methylation PCR that offers standardized determination of FMR1 methylation and CGG repeat length without southern blot analysis.

    Science.gov (United States)

    Grasso, Marina; Boon, Elles M J; Filipovic-Sadic, Stela; van Bunderen, Patrick A; Gennaro, Elena; Cao, Ru; Latham, Gary J; Hadd, Andrew G; Coviello, Domenico A

    2014-01-01

    Fragile X syndrome and associated disorders are characterized by the number of CGG repeats and methylation status of the FMR1 gene for which Southern blot (SB) historically has been required for analysis. This study describes a simple PCR-only workflow (mPCR) to replace SB analysis, that incorporates novel procedural controls, treatment of the DNA in separate control and methylation-sensitive restriction endonuclease reactions, amplification with labeled primers, and two-color amplicon sizing by capillary electrophoresis. mPCR was evaluated in two independent laboratories with 76 residual clinical samples that represented typical and challenging fragile X alleles in both males and females. mPCR enabled superior size resolution and analytical sensitivity for size and methylation mosaicism compared to SB. Full mutation mosaicism was detected down to 1% in a background of 99% normal allele with 50- to 100-fold less DNA than required for SB. A low level of full mutation mosaicism in one sample was detected using mPCR but not observed using SB. Overall, the sensitivity for detection of full mutation alleles was 100% (95% CI: 89%-100%) with an accuracy of 99% (95% CI: 93%-100%). mPCR analysis of DNA from individuals with Klinefelter and Turner syndromes, and DNA from sperm and blood, were consistent with SB. As such, mPCR enables accurate, sensitive, and standardized methods of FMR1 analysis that can harmonize results across different laboratories.

  4. Huntington CAG repeat size does not modify onset age in familial Parkinson’s disease: The GenePD Study

    Science.gov (United States)

    McNicoll, Christopher F.; Latourelle, Jeanne C.; MacDonald, Marcy E.; Lew, Mark F.; Suchowersky, Oksana; Klein, Christine; Golbe, Lawrence I.; Mark, Margery H.; Growdon, John H.; Wooten, G. Frederick; Watts, Ray L.; Guttman, Mark; Racette, Brad A.; Perlmutter, Joel S.; Ahmed, Anwar; Shill, Holly A.; Singer, Carlos; Saint-Hilaire, Marie H.; Massood, Tiffany; Huskey, Karen W.; DeStefano, Anita L.; Gillis, Tammy; Mysore, Jayalakshmi; Goldwurm, Stefano; Pezzoli, Gianni; Baker, Kenneth B.; Itin, Ilia; Litvan, Irene; Nicholson, Garth; Corbett, Alastair; Nance, Martha; Drasby, Edward; Isaacson, Stuart; Burn, David J.; Chinnery, Patrick F.; Pramstaller, Peter P.; Al-hinti, Jomana; Moller, Anette T.; Ostergaard, Karen; Sherman, Scott J.; Roxburgh, Richard; Snow, Barry; Slevin, John T.; Cambi, Franca; Gusella, James F.; Myers, Richard H.

    2009-01-01

    The ATP/ADP ratio reflects mitochondrial function and has been reported to be influenced by the size of the Huntington disease gene (HD) repeat. Impaired mitochondrial function has long been implicated in the pathogenesis of Parkinson’s disease (PD) and therefore, we evaluated the relationship of the HD CAG repeat size to PD onset age in a large sample of familial PD cases. PD affected siblings (n=495) with known onset ages from 248 families, were genotyped for the HD CAG repeat. Genotyping failed in 11 cases leaving 484 for analysis, including 35 LRRK2 carriers. All cases had HD CAG repeats (range 15 to 34) below the clinical range for HD, although 5.2 percent of the sample (n=25) had repeats in the intermediate range (the intermediate range lower limit=27; upper limit=35 repeats), suggesting that the prevalence of intermediate allele carriers in the general population is significant. No relation between the HD CAG repeat size and the age at onset for PD was found in this sample of familial PD. PMID:18649400

  5. Mature clustered, regularly interspaced, short palindromic repeats RNA (crRNA) length is measured by a ruler mechanism anchored at the precursor processing site.

    Science.gov (United States)

    Hatoum-Aslan, Asma; Maniv, Inbal; Marraffini, Luciano A

    2011-12-27

    Precise RNA processing is fundamental to all small RNA-mediated interference pathways. In prokaryotes, clustered, regularly interspaced, short palindromic repeats (CRISPR) loci encode small CRISPR RNAs (crRNAs) that protect against invasive genetic elements by antisense targeting. CRISPR loci are transcribed as a long precursor that is cleaved within repeat sequences by CRISPR-associated (Cas) proteins. In many organisms, this primary processing generates crRNA intermediates that are subject to additional nucleolytic trimming to render mature crRNAs of specific lengths. The molecular mechanisms underlying this maturation event remain poorly understood. Here, we defined the genetic requirements for crRNA primary processing and maturation in Staphylococcus epidermidis. We show that changes in the position of the primary processing site result in extended or diminished maturation to generate mature crRNAs of constant length. These results indicate that crRNA maturation occurs by a ruler mechanism anchored at the primary processing site. We also show that maturation is mediated by specific cas genes distinct from those genes involved in primary processing, showing that this event is directed by CRISPR/Cas loci.

  6. Stress appraisals and cellular aging: a key role for anticipatory threat in the relationship between psychological stress and telomere length.

    Science.gov (United States)

    O'Donovan, Aoife; Tomiyama, A Janet; Lin, Jue; Puterman, Eli; Adler, Nancy E; Kemeny, Margaret; Wolkowitz, Owen M; Blackburn, Elizabeth H; Epel, Elissa S

    2012-05-01

    Chronic psychological stress is a risk factor for multiple diseases of aging. Accelerated cellular aging as indexed by short telomere length has emerged as a potential common biological mechanism linking various forms of psychological stress and diseases of aging. Stress appraisals determine the degree and type of biological stress responses and altered stress appraisals may be a common psychological mechanism linking psychological stress and diseases of aging. However, no previous studies have examined the relationship between stress appraisals and telomere length. We exposed chronically stressed female caregivers and non-caregiving controls (N=50; M age=62.14±6.10) to a standardized acute laboratory stressor and measured their anticipatory and retrospective threat and challenge appraisals of the stressor. We hypothesized that threat and challenge appraisals would be associated with shorter and longer telomere length respectively, and that chronic caregiving stress would influence telomere length through altered stress appraisals. Higher anticipatory threat appraisals were associated with shorter age-adjusted telomere length (β=-.32, p=.03), but challenge appraisals and retrospective threat appraisals showed no independent association with telomere length. Caregivers reported significantly higher anticipatory (β=-.36, p=.006) and retrospective (β=-.29, p=.03) threat appraisals than controls, but similar challenge appraisals. Although there was no significant main effect of caregiver status on telomere length, caregiving had a significant indirect effect on telomere length through anticipatory threat appraisals. Exaggerated anticipatory threat appraisals may be a common and modifiable psychological mechanism of psychological stress effects on cellular aging.

  7. Leukocyte Telomere Length in Young Adults Born Preterm: Support for Accelerated Biological Ageing.

    Directory of Open Access Journals (Sweden)

    Carolina C J Smeets

    Full Text Available Subjects born preterm have an increased risk for age-associated diseases, such as cardiovascular disease in later life, but the underlying causes are largely unknown. Shorter leukocyte telomere length (LTL, a marker of biological age, is associated with increased risk of cardiovascular disease.To compare LTL between subjects born preterm and at term and to assess if LTL is associated with other putative cardiovascular risk factors at young adult age.We measured mean LTL in 470 young adults. LTL was measured using a quantitative PCR assay and expressed as T/S ratio. We analyzed the influence of gestational age on LTL and compared LTL between subjects born preterm (n = 186 and at term (n = 284. Additionally, we analyzed the correlation between LTL and potential risk factors of cardiovascular disease.Gestational age was positively associated with LTL (r = 0.11, p = 0.02. Subjects born preterm had shorter LTL (mean (SD T/S ratio = 3.12 (0.44 than subjects born at term (mean (SD T/S ratio = 3.25 (0.46, p = 0.003. The difference remained significant after adjustment for gender and size at birth (p = 0.001. There was no association of LTL with any one of the putative risk factors analyzed.Young adults born preterm have shorter LTL than young adults born at term. Although we found no correlation between LTL and risk for CVD at this young adult age, this biological ageing indicator may contribute to CVD and other adult onset diseases at a later age in those born preterm.

  8. Modelling Developmental Changes in Repeated-Sprint Ability by Chronological and Skeletal Ages in Young Soccer Players

    NARCIS (Netherlands)

    Valente-dos-Santos, J.; Coelho-e-Silva, M. J.; Martins, R. A.; Figueiredo, A. J.; Cyrino, E. S.; Sherar, L. B.; Vaeyens, R.; Huijgen, B. C. H.; Elferink-Gemser, M. T.; Malina, R. M.

    2012-01-01

    This study investigated the influence of chronological (CA) and skeletal ages (SA), anthropometry, aerobic endurance and lower limb explosive strength on developmental changes in repeated-sprint ability (RSA) in soccer players aged 11-17 years. Participants were annually followed over 5 years, resul

  9. Modelling Developmental Changes in Repeated-Sprint Ability by Chronological and Skeletal Ages in Young Soccer Players

    NARCIS (Netherlands)

    Valente-dos-Santos, J.; Coelho-e-Silva, M. J.; Martins, R. A.; Figueiredo, A. J.; Cyrino, E. S.; Sherar, L. B.; Vaeyens, R.; Huijgen, B. C. H.; Elferink-Gemser, M. T.; Malina, R. M.

    2012-01-01

    This study investigated the influence of chronological (CA) and skeletal ages (SA), anthropometry, aerobic endurance and lower limb explosive strength on developmental changes in repeated-sprint ability (RSA) in soccer players aged 11-17 years. Participants were annually followed over 5 years, resul

  10. Modelling Developmental Changes in Repeated-Sprint Ability by Chronological and Skeletal Ages in Young Soccer Players

    NARCIS (Netherlands)

    Valente-dos-Santos, J.; Coelho-e-Silva, M. J.; Martins, R. A.; Figueiredo, A. J.; Cyrino, E. S.; Sherar, L. B.; Vaeyens, R.; Huijgen, B. C. H.; Elferink-Gemser, M. T.; Malina, R. M.

    2012-01-01

    This study investigated the influence of chronological (CA) and skeletal ages (SA), anthropometry, aerobic endurance and lower limb explosive strength on developmental changes in repeated-sprint ability (RSA) in soccer players aged 11-17 years. Participants were annually followed over 5 years,

  11. Corepressor effect on androgen receptor activity varies with the length of the CAG encoded polyglutamine repeat and is dependent on receptor/corepressor ratio in prostate cancer cells.

    Science.gov (United States)

    Buchanan, Grant; Need, Eleanor F; Barrett, Jeffrey M; Bianco-Miotto, Tina; Thompson, Vanessa C; Butler, Lisa M; Marshall, Villis R; Tilley, Wayne D; Coetzee, Gerhard A

    2011-08-01

    The response of prostate cells to androgens reflects a combination of androgen receptor (AR) transactivation and transrepression, but how these two processes differ mechanistically and influence prostate cancer risk and disease outcome remain elusive. Given recent interest in targeting AR transrepressive processes, a better understanding of AR/corepressor interaction and responses is warranted. Here, we used transactivation and interaction assays with wild-type and mutant ARs, and deletion AR fragments, to dissect the relationship between AR and the corepressor, silencing mediator for retinoic acid and thyroid hormone receptors (SMRT). We additionally tested how these processes are influenced by AR agonist and antagonist ligands, as well as by variation in the polyglutamine tract in the AR amino terminal domain (NTD), which is encoded by a polymorphic CAG repeat in the gene. SMRT was recruited to the AR ligand binding domain by agonist ligand, and as determined by the effect of strategic mutations in activation function 2 (AF-2), requires a precise conformation of that domain. A distinct region of SMRT also mediated interaction with the AR-NTD via the transactivation unit 5 (TAU5; residues 315-538) region. The degree to which SMRT was able to repress AR increased from 17% to 56% as the AR polyglutamine repeat length was increased from 9 to 42 residues, but critically this effect could be abolished by increasing the SMRT:AR molar ratio. These data suggest that the extent to which the CAG encoded polyglutamine repeat influences AR activity represents a balance between corepressor and coactivator occupancy of the same ligand-dependent and independent AR interaction surfaces. Changes in the homeostatic relationship of AR to these molecules, including SMRT, may explain the variable penetrance of the CAG repeat and the loss of AR signaling flexibility in prostate cancer progression.

  12. IS1630 of Mycoplasma fermentans, a Novel IS30-Type Insertion Element That Targets and Duplicates Inverted Repeats of Variable Length and Sequence during Insertion

    Science.gov (United States)

    Calcutt, Michael J.; Lavrrar, Jennifer L.; Wise, Kim S.

    1999-01-01

    A new insertion sequence (IS) of Mycoplasma fermentans is described. This element, designated IS1630, is 1,377 bp long and has 27-bp inverted repeats at the termini. A single open reading frame (ORF), predicted to encode a basic protein of either 366 or 387 amino acids (depending on the start codon utilized), occupies most of this compact element. The predicted translation product of this ORF has homology to transposases of the IS30 family of IS elements and is most closely related (27% identical amino acid residues) to the product of the prototype of the group, IS30. Multiple copies of IS1630 are present in the genomes of at least two M. fermentans strains. Characterization and comparison of nine copies of the element revealed that IS1630 exhibits unusual target site specificity and, upon insertion, duplicates target sequences in a manner unlike that of any other IS element. IS1630 was shown to have the striking ability to target and duplicate inverted repeats of variable length and sequence during transposition. IS30-type elements typically generate 2- or 3-bp target site duplications, whereas those created by IS1630 vary between 19 and 26 bp. With the exception of two recently reported IS4-type elements which have the ability to generate variable large duplications (B. B. Plikaytis, J. T. Crawford, and T. M. Shinnick, J. Bacteriol. 180:1037–1043, 1998; E. M. Vilei, J. Nicolet, and J. Frey, J. Bacteriol. 181:1319–1323, 1999), such large direct repeats had not been observed for other IS elements. Interestingly, the IS1630-generated duplications are all symmetrical inverted repeat sequences that are apparently derived from rho-independent transcription terminators of neighboring genes. Although the consensus target site for IS30 is almost palindromic, individual target sites possess considerably less inverted symmetry. In contrast, IS1630 appears to exhibit an increased stringency for inverted repeat recognition, since the majority of target sites had no

  13. Hierarchical Bayesian analysis to incorporate age uncertainty in growth curve analysis and estimates of age from length: Florida manatee (Trichechus manatus) carcasses

    Science.gov (United States)

    Schwarz, L.K.; Runge, M.C.

    2009-01-01

    Age estimation of individuals is often an integral part of species management research, and a number of ageestimation techniques are commonly employed. Often, the error in these techniques is not quantified or accounted for in other analyses, particularly in growth curve models used to describe physiological responses to environment and human impacts. Also, noninvasive, quick, and inexpensive methods to estimate age are needed. This research aims to provide two Bayesian methods to (i) incorporate age uncertainty into an age-length Schnute growth model and (ii) produce a method from the growth model to estimate age from length. The methods are then employed for Florida manatee (Trichechus manatus) carcasses. After quantifying the uncertainty in the aging technique (counts of ear bone growth layers), we fit age-length data to the Schnute growth model separately by sex and season. Independent prior information about population age structure and the results of the Schnute model are then combined to estimate age from length. Results describing the age-length relationship agree with our understanding of manatee biology. The new methods allow us to estimate age, with quantified uncertainty, for 98% of collected carcasses: 36% from ear bones, 62% from length.

  14. The impact of repeated marathon running on cardiovascular function in the aging population

    Directory of Open Access Journals (Sweden)

    Karlstedt Erin

    2012-08-01

    Full Text Available Abstract Background Several studies have correlated elevations in cardiac biomarkers of injury post marathon with transient and reversible right ventricular (RV systolic dysfunction as assessed by both transthoracic echocardiography (TTE and cardiovascular magnetic resonance (CMR. Whether or not permanent myocardial injury occurs due to repeated marathon running in the aging population remains controversial. Objectives To assess the extent and severity of cardiac dysfunction after the completion of full marathon running in individuals greater than 50 years of age using cardiac biomarkers, TTE, cardiac computed tomography (CCT, and CMR. Methods A total of 25 healthy volunteers (21 males, 55 ± 4 years old from the 2010 and 2011 Manitoba Full Marathons (26.2 miles were included in the study. Cardiac biomarkers and TTE were performed one week prior to the marathon, immediately after completing the race and at one-week follow-up. CMR was performed at baseline and within 24 hours of completion of the marathon, followed by CCT within 3 months of the marathon. Results All participants demonstrated an elevated cTnT post marathon. Right atrial and ventricular volumes increased, while RV systolic function decreased significantly immediately post marathon, returning to baseline values one week later. Of the entire study population, only two individuals demonstrated late gadolinium enhancement of the subendocardium in the anterior wall of the left ventricle, with evidence of stenosis of the left anterior descending artery on CCT. Conclusions Marathon running in individuals over the age of 50 is associated with a transient, yet reversible increase in cardiac biomarkers and RV systolic dysfunction. The presence of myocardial fibrosis in older marathon athletes is infrequent, but when present, may be due to underlying occult coronary artery disease.

  15. Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder

    NARCIS (Netherlands)

    Boks, Marco P.; van Mierlo, Hans C.; Rutten, Bart P. F.; Radstake, Timothy R. D. J.; De Witte, Lot; Geuze, Elbert; Horvath, Steve; Schalkwyk, Leonard C.; Vinkers, Christiaan H.; Broen, Jasper C. A.; Vermetten, Eric

    2015-01-01

    Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on ageing at the cellular level. A newly derived tool provides an additional means to investigate cellular ageing by estimating epigenetic age based on DNA methyla

  16. Expressed Sequence Tags Analysis and Design of Simple Sequence Repeats Markers from a Full-Length cDNA Library in Perilla frutescens (L.

    Directory of Open Access Journals (Sweden)

    Eun Soo Seong

    2015-01-01

    Full Text Available Perilla frutescens is valuable as a medicinal plant as well as a natural medicine and functional food. However, comparative genomics analyses of P. frutescens are limited due to a lack of gene annotations and characterization. A full-length cDNA library from P. frutescens leaves was constructed to identify functional gene clusters and probable EST-SSR markers via analysis of 1,056 expressed sequence tags. Unigene assembly was performed using basic local alignment search tool (BLAST homology searches and annotated Gene Ontology (GO. A total of 18 simple sequence repeats (SSRs were designed as primer pairs. This study is the first to report comparative genomics and EST-SSR markers from P. frutescens will help gene discovery and provide an important source for functional genomics and molecular genetic research in this interesting medicinal plant.

  17. Telomere length change plateaus at 4 years of age in Latino children: associations with baseline length and maternal change.

    Science.gov (United States)

    Wojcicki, Janet M; Shiboski, Stephen; Heyman, Melvin B; Elwan, Deena; Lin, Jue; Blackburn, Elizabeth; Epel, Elissa

    2016-06-01

    Telomeres are the protective complexes at the end of chromosomes, required for genomic stability. Little is known about predictors of attrition in young children or the relationship between parental and child patterns of telomere change. Telomere length was assessed twice over one year, at 4 and at 5 years of age, in Latino preschool children (n = 77) and their mothers (n = 70) in whole blood leukocytes. Maternal and child rates of attrition during the same time period were compared in 70 mother-child pairs. More children showed lengthened telomeres over one year compared to their mothers and very few children showed attrition (2.6 %). Approximately 31 % of children and 16 % of mothers displayed lengthening over one year while 66 % of children showed maintenance in contrast with 74 % of mothers. The strongest predictor for child telomere length change was child's baseline telomere length (r = -0.61, p telomere length, the relationship between child and maternal rate of change trended towards significance (Coeff = 0.20, 95 % CI -0.03 to 0.43; p = 0.08). We found primarily maintenance and lengthening from 4 to 5 years of age in children, with minimal telomere attrition, indicating that most of the telomere loss happens in the first 4 years, plateauing by age 4. Lastly, we found close to 10 % of the variance in rate of change in children shared by mothers. While some of this shared variance is genetic, there are likely environmental factors that need to be further identified that impact rate of telomere length change.

  18. TPR重复和ELTR排型:重复的长度变化是一种功能进化的机制%TPR repeats and ELTR pattern: length variation as a function evolution mechanism

    Institute of Scientific and Technical Information of China (English)

    杨克迁

    2007-01-01

    TPR repeat was originally defined as a 34 amino acid structural repeat (TPR-34). Equal length tandem repeats (ELTR) was proposed to represent the ancestral repeat pattern. Length polymorphism of TPR repeats was analyzed using PATTINPROT, two new versions of TPR repeat of 40 and 42 amino acids were identified. These 'long' TPRs endow new functional capacities to the resulting proteins. A strong correlation between varied lengths and new functions supports the hypothesis that length variation is an underlying mechanism for the function evolution of repeat containing proteins.%TPR 重复最初定义为一个34个氨基酸的蛋白结构重复.本文用PATTINPROT软件对基因库中TPR 重复长度多样性进行了分析,发现40和42个氨基酸TPR 重复大量存在. 含40和42个氨基酸TPR重复序列蛋白的功能分析说明,这些长的TPR重复可以赋予蛋白新的功能.根据以上分析,提出重复序列的长度变化可能是功能进化的一种发生机制.

  19. Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging.

    Science.gov (United States)

    Lindqvist, Daniel; Epel, Elissa S; Mellon, Synthia H; Penninx, Brenda W; Révész, Dóra; Verhoeven, Josine E; Reus, Victor I; Lin, Jue; Mahan, Laura; Hough, Christina M; Rosser, Rebecca; Bersani, F Saverio; Blackburn, Elizabeth H; Wolkowitz, Owen M

    2015-08-01

    Many psychiatric illnesses are associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, certain psychiatric illnesses may be associated with accelerated cellular aging, evidenced by shortened leukocyte telomere length (LTL), which could underlie this association. Shortened LTL reflects a cell's mitotic history and cumulative exposure to inflammation and oxidation as well as the availability of telomerase, a telomere-lengthening enzyme. Critically short telomeres can cause cells to undergo senescence, apoptosis or genomic instability, and shorter LTL correlates with poorer health and predicts mortality. Emerging data suggest that LTL may be reduced in certain psychiatric illnesses, perhaps in proportion to exposure to the psychiatric illnesses, although conflicting data exist. Telomerase has been less well characterized in psychiatric illnesses, but a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this article, studies on LTL and telomerase activity in psychiatric illnesses are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in psychiatric illnesses could lead to re-conceptualizing them as systemic illnesses with manifestations inside and outside the brain and could identify new treatment targets.

  20. Q-FISH measurement of hepatocyte telomere lengths in donor liver and graft after pediatric living-donor liver transplantation: donor age affects telomere length sustainability.

    Directory of Open Access Journals (Sweden)

    Youichi Kawano

    Full Text Available Along with the increasing need for living-donor liver transplantation (LDLT, the issue of organ shortage has become a serious problem. Therefore, the use of organs from elderly donors has been increasing. While the short-term results of LDLT have greatly improved, problems affecting the long-term outcome of transplant patients remain unsolved. Furthermore, since contradictory data have been reported with regard to the relationship between donor age and LT/LDLT outcome, the question of whether the use of elderly donors influences the long-term outcome of a graft after LT/LDLT remains unsettled. To address whether hepatocyte telomere length reflects the outcome of LDLT, we analyzed the telomere lengths of hepatocytes in informative biopsy samples from 12 paired donors and recipients (grafts of pediatric LDLT more than 5 years after adult-to-child LDLT because of primary biliary atresia, using quantitative fluorescence in situ hybridization (Q-FISH. The telomere lengths in the paired samples showed a robust relationship between the donor and grafted hepatocytes (r = 0.765, p = 0.0038, demonstrating the feasibility of our Q-FISH method for cell-specific evaluation. While 8 pairs showed no significant difference between the telomere lengths for the donor and the recipient, the other 4 pairs showed significantly shorter telomeres in the recipient than in the donor. Multiple regression analysis revealed that the donors in the latter group were older than those in the former (p = 0.001. Despite the small number of subjects, this pilot study indicates that donor age is a crucial factor affecting telomere length sustainability in hepatocytes after pediatric LDLT, and that the telomeres in grafted livers may be elongated somewhat longer when the grafts are immunologically well controlled.

  1. Repeatability of swept-source optical coherence tomography retinal and choroidal thickness measurements in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Hanumunthadu, Daren; Ilginis, Tomas; Restori, Marie

    2017-01-01

    BACKGROUND: The aim was to determine the intrasession repeatability of swept-source optical coherence tomography (SS-OCT)-derived retinal and choroidal thickness measurements in eyes with neovascular age-related macular degeneration (nAMD). METHODS: A prospective study consisting of patients with...

  2. Gene expression profiling of R6/2 transgenic mice with different CAG repeat lengths reveals genes associated with disease onset and progression in Huntington's disease.

    Science.gov (United States)

    Tang, Bin; Seredenina, Tamara; Coppola, Giovanni; Kuhn, Alexandre; Geschwind, Daniel H; Luthi-Carter, Ruth; Thomas, Elizabeth A

    2011-06-01

    R6/2 transgenic mice with expanded CAG repeats (>300) have a surprisingly prolonged disease progression and longer lifespan than prototypical parent R6/2 mice (carrying 150 CAGs); however, the mechanism of this phenotype amelioration is unknown. We compared gene expression profiles in the striatum of R6/2 transgenic mice carrying ~300 CAG repeats (R6/2(Q300) transgenic mice) to those carrying ~150 CAG repeats (R6/2(Q150) transgenic mice) and littermate wildtype controls in order to identify genes that may play determinant roles in the time course of phenotypic expression in these mice. Of the top genes showing concordant expression changes in the striatum of both R6/2 lines, 85% were decreased in expression, while discordant expression changes were observed mostly for genes upregulated in R6/2(Q300) transgenic mice. Upregulated genes in the R6/2(Q300) mice were associated with the ubiquitin ligase complex, cell adhesion, protein folding, and establishment of protein localization. We qPCR-validated increases in expression of genes related to the latter category, including Lrsam1, Erp29, Nasp, Tap1, Rab9b, and Pfdn5 in R6/2(Q300) mice, changes that were not observed in R6/2 mice with shorter CAG repeats, even in late stages (i.e., 12 weeks of age). We further tested Lrsam1 and Erp29, the two genes showing the greatest upregulation in R6/2(Q300) transgenic mice, for potential neuroprotective effects in primary striatal cultures overexpressing a mutated human huntingtin (htt) fragment. Overexpression of Lrsam1 prevented the loss of NeuN-positive cell bodies in htt171-82Q cultures, concomitant with a reduction of nuclear htt aggregates. Erp29 showed no significant effects in this model. This is consistent with the distinct pattern of htt inclusion localization observed in R6/2(Q300) transgenic mice, in which smaller cytoplasmic inclusions represent the major form of insoluble htt in the cell, as opposed to large nuclear inclusions observed in R6/2(Q150) transgenic mice

  3. Age-related declines and disease-associated variation in immune cell telomere length in a wild mammal.

    Directory of Open Access Journals (Sweden)

    Christopher Beirne

    Full Text Available Immunosenescence, the deterioration of immune system capability with age, may play a key role in mediating age-related declines in whole-organism performance, but the mechanisms that underpin immunosenescence are poorly understood. Biomedical research on humans and laboratory models has documented age and disease related declines in the telomere lengths of leukocytes ('immune cells', stimulating interest their having a potentially general role in the emergence of immunosenescent phenotypes. However, it is unknown whether such observations generalise to the immune cell populations of wild vertebrates living under ecologically realistic conditions. Here we examine longitudinal changes in the mean telomere lengths of immune cells in wild European badgers (Meles meles. Our findings provide the first evidence of within-individual age-related declines in immune cell telomere lengths in a wild vertebrate. That the rate of age-related decline in telomere length appears to be steeper within individuals than at the overall population level raises the possibility that individuals with short immune cell telomeres and/or higher rates of immune cell telomere attrition may be selectively lost from this population. We also report evidence suggestive of associations between immune cell telomere length and bovine tuberculosis infection status, with individuals detected at the most advanced stage of infection tending to have shorter immune cell telomeres than disease positive individuals. While male European badgers are larger and show higher rates of annual mortality than females, we found no evidence of a sex difference in either mean telomere length or the average rate of within-individual telomere attrition with age. Our findings lend support to the view that age-related declines in the telomere lengths of immune cells may provide one potentially general mechanism underpinning age-related declines in immunocompetence in natural populations.

  4. Association between leukocyte telomere length and bone mineral density in women 25-93 years of age

    DEFF Research Database (Denmark)

    Nielsen, Barbara Rubek; Linneberg, Allan; Bendix, Laila

    2015-01-01

    Leukocyte telomere length (LTL) and bone mineral density (BMD) are associated with health and mortality. Because osteoporosis is an age-related condition and LTL is considered to be a biomarker of aging, we hypothesized that shorter LTL could predict lower BMD. The aim of our study was to assess...

  5. On the Lengths, Colors and Ages of 18 Face-On Bars

    CERN Document Server

    Gadotti, D A; Gadotti, Dimitri A.; Souza, Ronaldo E. de

    2005-01-01

    Along with a brief analysis we present data obtained from BVRI and Ks images of a sample of 19 galaxies (18 barred and 1 unbarred) which will be further explored in a future paper. We measured the lengths and colors of the bars, created color maps and estimated global color gradients. Applying a method developed in a companion paper, we could distinguish for 7 galaxies in our sample those whose bars have been recently formed from the ones with already evolved bars. We estimated an average difference in the optical colors between young and evolved bars that may be translated to an age difference of the order of 10 Gyr, meaning that bars may be, at least in some cases, long standing structures. Moreover, our results show that, on average, evolved bars are longer than young bars. This seems to indicate that, during its evolution, a bar grows longer by capturing stars from the disk, in agreement with recent numerical and analytical results. Although the statistical significance of these results is low, and furthe...

  6. Length and weight of very low birth weight infants in Germany at 2 years of age: does it matter at what age they start complementary food?

    Science.gov (United States)

    Spiegler, J; Eisemann, N; Ehlers, S; Orlikowsky, T; Kannt, O; Herting, E; Göpel, W

    2015-06-01

    We analysed at what age parents start complementary food in very low birth weight infants, determined risk factors for early introduction of complementary food (post-term age) and analysed whether the age at introduction of complementary food influences height or weight at 2 years of age. Parents of premature infants born in 2009-2011 answered questionnaires regarding introduction of complementary food in the first year of life (N=2262) and were followed up at a post-term age of 2 years (N=981). Length and weight were compared with full-term infants from the KiGGs study. Logistic and linear regression analyses were conducted to study predictors for early introduction of complementary food and the influence of age at introduction of complementary food on later height and weight. Average age at introduction of complementary food was 3.5 months post-term age. The lower the gestational age at birth, the earlier (post-term age) vegetables and meat were introduced. Age at introduction of complementary food was influenced by intrauterine growth restriction, gestational age at birth, maternal education and a developmental delay perceived by the parents. Length and weight at a post-term age of 2 years was not negatively influenced by early introduction of complementary food. VLBW infants are introduced to complementary food on average before a post-term age of 4 months. There was no negative effect of early introduction of complementary food on height and weight at 2 years of age.

  7. Amplification of a single-locus variable-number direct repeats with restriction fragment length polymorphism (DR-PCR/RFLP) for genetic typing of Acinetobacter baumannii strains.

    Science.gov (United States)

    Nowak-Zaleska, Alicja; Krawczyk, Beata; Kotłowski, Roman; Mikucka, Agnieszka; Gospodarek, Eugenia

    2008-01-01

    In search of an effective DNA typing technique for Acinetobacter baumannii strains for hospital epidemiology use, the performance and convenience of a new target sequence was evaluated. Using known genomic sequences of Acinetobacter baumannii strains AR 319754 and ATCC 17978, we developed single-locus variable-number direct-repeat analysis using polymerase chain reaction-restriction fragment length polymorphism (DR-PCR/RFLP) method. A total of 90 Acinetobacter baumannii strains isolated from patients of the Clinical Hospital in Bydgoszcz, Poland, were examined. Initially, all strains were typed using macrorestriction analysis of the chromosomal DNA by pulsed-field gel electrophoresis (REA-PFGE). Digestion of the chromosomal DNA with the ApaI endonuclease and separation of the fragments by PFGE revealed 21 unique types. Application of DR-PCR/RFLP resulted in recognition of 12 clusters. The results showed that the DR-PCR/RFLP method is less discriminatory than REA-PFGE, however, the novel genotyping method can be used as an alternative technique for generating DNA profiles in epidemiological studies of intra-species genetic relatedness of Acinetobacter baumannii strains.

  8. Clustering of Beijing genotype Mycobacterium tuberculosis isolates from the Mekong delta in Vietnam on the basis of variable number of tandem repeat versus restriction fragment length polymorphism typing

    Directory of Open Access Journals (Sweden)

    Huyen Mai NT

    2013-02-01

    Full Text Available Abstract Background In comparison to restriction fragment length polymorphism (RFLP typing, variable number of tandem repeat (VNTR typing is easier to perform, faster and yields results in a simple, numerical format. Therefore, this technique has gained recognition as the new international gold standard in typing of Mycobacterium tuberculosis. However, some reports indicated that VNTR typing may be less suitable for Beijing genotype isolates. We therefore compared the performance of internationally standardized RFLP and 24 loci VNTR typing to discriminate among 100 Beijing genotype isolates from the Southern Vietnam. Methods Hundred Beijing genotype strains defined by spoligotyping were randomly selected and typed by RFLP and VNTR typing. The discriminatory power of VNTR and RFLP typing was compared using the Bionumerics software. Results Among 95 Beijing strains available for analysis, 14 clusters were identified comprising 34 strains and 61 unique profiles in 24 loci VNTR typing ((Hunter Gaston Discrimination Index (HGDI = 0.994. 13 clusters containing 31 strains and 64 unique patterns in RFLP typing (HGDI = 0.994 were found. Nine RFLP clusters were subdivided by VNTR typing and 12 VNTR clusters were split by RFLP. Five isolates (5% revealing double alleles or no signal in two or more loci in VNTR typing could not be analyzed. Conclusions Overall, 24 loci VNTR typing and RFLP typing had similar high-level of discrimination among 95 Beijing strains from Southern Vietnam. However, loci VNTR 154, VNTR 2461 and VNTR 3171 had hardly added any value to the level of discrimination.

  9. Repeatability of frequency of corrective foot pressure during balance control in children aged between 2 and 7.

    Science.gov (United States)

    Sobera, Małgorzata; Siedlecka, Bożena

    2010-01-01

    The frequency of corrective signal (the centre of corrective (COC) signal), which is the decomposition of COP (centre of pressure) and estimated COM (centre of mass) time series, is one of the indicators reflecting the quality of postural control during stance. Young children, in the period of intensive development, gradually improve the quality of postural control in a daily life. The purpose of this paper was to describe the time series of corrective centre of foot pressure repeatability in young children aged between 2 and 7 during body stability in natural stance position. 272 healthy children aged between 2 and 7 were divided into 6 age groups. Two AccuSway force platforms were used (one foot of the subject was on one platform, the second foot, on the other). The COP trajectories were the basis for the calculation of the frequency stability indices in frontal and sagittal planes for the left leg and right leg separately. The COC signals were collected by the method based on the Kuczyński viscoelastic model. In order to assess the repeatability, the concordance correlation coefficient (CCC) was used between the 1st and the 2nd trials, the 2nd and the 3rd trials, and the 1st and the 3rd trials. The maturation of postural control system goes rather slowly in two youngest groups which showed the poor repeatability in COC frequency between the 2nd and the 3rd years of life. From the 4th to the 7th year of life the inter-session repeatability rapidly increases in three consecutive trials. Poor difference of frequency concordance was found between the left and right lower limbs. It is concluded that the frequency of corrective foot pressure is the reliable indicator of postural control for children aged between 4 and 7, but not for younger ones.

  10. Telomere length behaves as biomarker of somatic redundancy rather than biological age

    NARCIS (Netherlands)

    Boonekamp, Jelle J.; Simons, Mirre J. P.; Hemerik, Lia; Verhulst, Simon

    2013-01-01

    Biomarkers of aging are essential to predict mortality and aging-related diseases. Paradoxically, age itself imposes a limitation on the use of known biomarkers of aging because their associations with mortality generally diminish with age. How this pattern arises is, however, not understood. With m

  11. Telomere length behaves as biomarker of somatic redundancy rather than biological age

    NARCIS (Netherlands)

    Boonekamp, J.J.; Simons, M.J.P.; Hemerik, L.; Verhulst, S.

    2013-01-01

    Biomarkers of aging are essential to predict mortality and aging related diseases. Paradoxically, age itself imposes a limitation on the use of known biomarkers of aging, because their associations with mortality generally diminish with age. How this pattern arises is however not understood. With me

  12. Telomere length behaves as biomarker of somatic redundancy rather than biological age

    NARCIS (Netherlands)

    Boonekamp, Jelle J.; Simons, Mirre J. P.; Hemerik, Lia; Verhulst, Simon

    2013-01-01

    Biomarkers of aging are essential to predict mortality and aging-related diseases. Paradoxically, age itself imposes a limitation on the use of known biomarkers of aging because their associations with mortality generally diminish with age. How this pattern arises is, however, not understood. With m

  13. Repeatability of swept-source optical coherence tomography retinal and choroidal thickness measurements in neovascular age-related macular degeneration.

    Science.gov (United States)

    Hanumunthadu, Daren; Ilginis, Tomas; Restori, Marie; Sagoo, Mandeep S; Tufail, Adnan; Balaggan, Kamaljit S; Patel, Praveen J

    2017-05-01

    The aim was to determine the intrasession repeatability of swept-source optical coherence tomography (SS-OCT)-derived retinal and choroidal thickness measurements in eyes with neovascular age-related macular degeneration (nAMD). A prospective study consisting of patients with active nAMD enrolled in the Distance of Choroid Study at Moorfields Eye Hospital, London. Patients underwent three 12×9 mm macular raster scans using the deep range imaging (DRI) OCT-1 SS-OCT (Topcon) device in a single imaging session. Retinal and choroidal thicknesses were calculated for the ETDRS macular subfields. Repeatability was calculated according to methods described by Bland and Altman. 39 eyes of 39 patients with nAMD were included with a mean (±SD) age of 73.9 (±7.2) years. The mean (±SD) retinal thickness of the central macular subfield was 225.7 μm (±12.4 μm). The repeatability this subfield, expressed as a percentage of the mean central macular subfield thickness, was 23.2%. The percentage repeatability of the other macular subfields ranged from 13.2% to 28.7%. The intrasession coefficient of repeatability of choroidal thickness of the central macular subfield was 57.2 μm with a mean choroidal thickness (±SD) of 181 μm (±15.8 μm). This study suggests that a change >23.2% of retinal thickness and 57.2 μm choroidal thickness in the central macular subfield is required to distinguish true clinical change from measurement variability when using the DRI OCT-1 device to manage patients with nAMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  14. A maximal cycle test with good validity and high repeatability in adults of all ages

    DEFF Research Database (Denmark)

    Eriksen, L; Tolstrup, J S; Larsen, Steen

    2014-01-01

    In 11 680 individuals (18-85 years) maximal oxygen consumption (VO2max) was estimated indirectly in a maximal cycle test using a prediction model developed in a young population (15-28 years). A subsample of 182 individuals (23-77 years) underwent 2 maximal cycle tests with VO2max estimated...... we suggest a new prediction model of VO2max. The maximal cycle test was highly repeatable....

  15. INSIG2 is Associated with Lower Gain in Weight-for-Length Between Birth and Age 6 Months

    Directory of Open Access Journals (Sweden)

    Ann Chen Wu

    2009-01-01

    Full Text Available Researchers have described the association of a common DNA polymorphism, rs7566605, near INSIG2 (insulin-induced gene 2 with obesity in multiple independent populations that include subjects ages 11–60 years.1 To our knowledge, no studies have examined the association of this polymorphism with weight status during early childhood. We explored the association of the rs7566605 polymorphism with weight-for-length among 319 children at 6 months and 3 years participating in Project Viva, a pre-birth cohort study. In contrast to studies of older individuals, CC homozygosity was associated with lower gain in weight-for-length z-score between birth and age 6 months than GG homozygosity or GC heterozygosity. At age 3, we did not find an association. The association of INSIG2 gene with obesity may change direction with age.

  16. A method for estimating age of medieval sub-adults from infancy to adulthood based on long bone length

    DEFF Research Database (Denmark)

    Primeau, Charlotte; Friis, Laila Saidane; Sejrsen, Birgitte;

    2016-01-01

    on a modern population (Maresh: Human growth and development () pp 155-200), and, lastly, based on archeological data with known ages (Rissech et al.: Forensic Sci Int 180 () 1-9). As growth of long bones is known to be non-linear it was tested if the regression model could be improved by applying a quadratic...... model. RESULTS: Comparison between estimated ages revealed that the modern data result in lower estimated ages when compared to the Danish regression equations. The estimated ages using the Danish regression equations and the regression equations developed by Rissech et al. (Forensic Sci Int 180 () 1......OBJECTIVES: To develop a series of regression equations for estimating age from length of long bones for archaeological sub-adults when aging from dental development cannot be performed. Further, to compare derived ages when using these regression equations, and two other methods. MATERIAL...

  17. Evaluation of skeletal and dental age using third molar calcification, condylar height and length of the mandibular body

    Directory of Open Access Journals (Sweden)

    Sunil Gupta Kedarisetty

    2015-01-01

    Full Text Available Aim: To identify the most reliable method for age estimation among three variables, that is, condylar height, length of mandibular body and third molar calcification by Demirjian′s method. Materials and Methods: Orthopantomograms and lateral cephalograms of 60 patients with equal gender ratio were included in the study, among each gender 15 subjects were below 18 years and 15 subjects were above 18 years. Lateral cephalograms were traced, height of condyle and mandibular body are measured manually on the tracing paper, OPG′s were observed on radiographic illuminator and maturity score of third molar calcification was noted according to Demirjian′s method. All the measurements were subjected to statistical analysis. Results: The results obtained are of no significant difference between estimated age and actual age with all three parameters (P > 0.9780 condylar height, P > 0.9515 length of mandibular body, P > 0.8611 third molar calcification. Among these three, length of mandibular body shows least standard error test (i.e. 0.188. Conclusion: Although all three parameters can be used for age estimation, length of mandibular body is more reliable followed by height of condyle and third molar calcification.

  18. Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder.

    Science.gov (United States)

    Boks, Marco P; van Mierlo, Hans C; Rutten, Bart P F; Radstake, Timothy R D J; De Witte, Lot; Geuze, Elbert; Horvath, Steve; Schalkwyk, Leonard C; Vinkers, Christiaan H; Broen, Jasper C A; Vermetten, Eric

    2015-01-01

    Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on ageing at the cellular level. A newly derived tool provides an additional means to investigate cellular ageing by estimating epigenetic age based on DNA methylation profiles. We therefore hypothesise that in a longitudinal study of traumatic stress both indicators of cellular ageing will show increased ageing. We expect that particularly in individuals that developed symptoms of post-traumatic stress disorder (PTSD) increases in these ageing parameters would stand out. From an existing longitudinal cohort study, ninety-six male soldiers were selected based on trauma exposure and the presence of symptoms of PTSD. All military personnel were deployed in a combat zone in Afghanistan and assessed before and 6 months after deployment. The Self-Rating Inventory for PTSD was used to measure the presence of PTSD symptoms, while exposure to combat trauma during deployment was measured with a 19-item deployment experiences checklist. These groups did not differ for age, gender, alcohol consumption, cigarette smoking, military rank, length, weight, or medication use. In DNA from whole blood telomere length was measured and DNA methylation levels were assessed using the Illumina 450K DNA methylation arrays. Epigenetic ageing was estimated using the DNAm age estimator procedure. The association of trauma with telomere length was in the expected direction but not significant (B=-10.2, p=0.52). However, contrary to our expectations, development of PTSD symptoms was associated with the reverse process, telomere lengthening (B=1.91, p=0.018). In concordance, trauma significantly accelerated epigenetic ageing (B=1.97, p=0.032) and similar to the findings in telomeres, development of PTSD symptoms was inversely associated with epigenetic ageing (B=-0.10, p=0.044). Blood cell count, medication and premorbid early life trauma exposure did not

  19. Telomere length and anaemia in old age: results from the Newcastle 85-plus Study* and the Leiden 85-plus Study

    Science.gov (United States)

    Den Elzen, Wendy P. J.; Martin-Ruiz, Carmen; von Zglinicki, Thomas; Westendorp, Rudi G. J.; Kirkwood, Thomas B. L.; Gussekloo, Jacobijn

    2011-01-01

    Background: reduced telomere length in blood cells has been associated with increased risk of multiple age-related diseases and is widely regarded as a general biomarker of ageing. Therefore, it is important to know both the extent and limitations of this association. We investigated the relation between telomere length and anaemia in two independent cohorts, with the prior expectation of adding anaemia to the list of conditions for which telomere reduction is a risk factor. Participants and methods: the present study is embedded in the Newcastle 85-plus Study and Leiden 85-plus Study, two population-based studies of inhabitants of Newcastle and North Tyneside, UK (n = 749) and Leiden, the Netherlands (n = 658) aged 85 and over. High-molecular-weight DNA was isolated from full fresh blood (Newcastle) and peripheral blood mononuclear cells samples (Leiden). Telomere length was measured as abundance of telomeric template versus a single gene by quantitative real-time polymerase chain reaction. Anaemia was defined according to World Health Organization criteria. Results: in both studies, no differences in median telomere length were observed between participants with anaemia and participants without anaemia (Newcastle: 2,846 bp (interquartile range (IQR) 2,433–3,630) versus 2,920 bp (IQR 2,425–3,570), P = 0.63; Leiden: 4,136 bp (IQR 3,879–4,428) versus 4,167 bp (IQR 3,893–4,501), P = 0.41). Telomere length also did not correlate with any other haematological parameter in both men and women. Conclusions: in contrast to other age-related diseases, telomere length is not associated with anaemia or any other haematological parameter in older individuals in the general population. PMID:21622673

  20. 端粒长度与肾衰老的研究现状%Research progress of telomere length on kidney aging

    Institute of Scientific and Technical Information of China (English)

    朱淑英

    2013-01-01

    Telomeres are highly conserved DNA repeats at the end of the linear chromosomes . Their main function is to cap the chromosome ends and maintain chromosomal stability and genetic integrity . Telomere length will shorten with every cell division , and will lose the function of the protection of chromosome when shortened to a certain length , and ultimately lead to cell senescence. Researches show that telomere shortening also exists in the aging kidney and meanwhile plays an important role in kindney aging .%端粒是位于线性染色体末端高度保守的DNA重复序列,是染色体末端的"保护帽",维护着染色体的稳定性及基因的完整性.端粒长度随着细胞的分裂而逐渐缩短到一定长度时,便失去了保护染色体的功能,并最终引起细胞衰老.研究表明,衰老的肾中也存在端粒的缩短,端粒的缩短在肾衰老中发挥着重要作用.

  1. Association of newborn diseases with weight/length ratio and the adequacy of weight for gestational age

    Directory of Open Access Journals (Sweden)

    José Ricardo Dias Bertagnon

    2011-09-01

    Full Text Available Objective: To compare the frequencies of newborn diseases in thosenewborns classified according to a weight/length rate and thoseclassified by the adequacy weight for gestational age. Methods: Aretrospective cross-sectional study by record assessment was carriedout enclosing all the live newborns at Hospital Geral do Grajaú, fromSeptember to December, 2009 (n =577 classified according to therate weight/length and also to the adequacy weight for gestationalage. The 10 and 90 percentiles of the weight/length distribution, nowdesignated as “indices” were calculated leading to the followingclassification: low index, for newborns below 54.8 g/cm; high index,for those over 75.8 g/cm; and average index, for the remainingnewborns. According to the adequacy weight for gestational age thenewborns were designated as pre-term for gestational age; term smallfor gestational age; appropriate term and large term. In this samplethere were no small and large pre-term or post-term newborns. Majordiseases were related to the index and adequacy extracts by the χ2test for a contingency table. Results: A significant association wasfound among low index, pre-term for gestational age newborns andterm small for gestational age; between average index and appropriatefor gestational age term newborns; and high index with large termappropriate for gestational age newborns (p< 0.001. Hypoglycemia(3.4% was associated to both low and high indices, to appropriatefor gestational age preterm newborns and to small for gestational ageterm newborns. Sepsis (3.1% was associated to both low index andpre-term appropriate for gestational age newborns. The respiratorydistress syndrome (1.3% was associated to low index and pre-termappropriate for gestational age newborns. Other respiratory distresssyndromes (3.8% were associated to low and high indices but notto the adequacy for gestational age classification. Jaundice (14.9%was not associated to the studied classifications

  2. Blood Telomere Length Attrition and Cancer Development in the Normative Aging Study Cohort

    Directory of Open Access Journals (Sweden)

    Lifang Hou

    2015-06-01

    Interpretation: Age-related BTL attrition was faster in cancer cases but their age-adjusted BTL attrition began decelerating as diagnosis approached. This may explain prior inconsistencies and help develop BTL as a cancer detection biomarker.

  3. Cognitive Change during the Life Course and Leukocyte Telomere Length in Late Middle-Aged Men

    DEFF Research Database (Denmark)

    Rask, Lene; Bendix, Laila; Harbo, Maria

    2016-01-01

    , it is unclear whether there is an association between cognitive decline and leukocyte telomere length. Objective: To examine the association between changes in cognitive function during adult life and leukocyte telomere length after adjusting for confounding factors such as education, mental health and life......% CI −0.17 to −0.01, p = 0.02) but was non-significant after adjusting for smoking, alcohol consumption, leisure time activity, BMI, cholesterol, current cognitive function, depression and education (adjusted difference β = −0.07, 95% CI −0.16 to −0.01, p = 0.08). Conclusion and Relevance: Preclinical...

  4. Correlation of Mandible Length and Dental Cacilfication Stages on the Deutero Malay Group Aged 8-16 Years

    Directory of Open Access Journals (Sweden)

    Fifi Siswanto

    2013-07-01

    Full Text Available Evaluation of individual maturity status takes an important role in selecting of the orthodontic treatment plans, especially for the growing age patient. This is mostly related to use of functional appliances and surgical approaches in some cases of skeletal discrepancy. Previous researches hae demonstrated the significant correlation between the mandible length and the cervical vertebrae maturation in Deutero-Malay group. The significant correlation between the cervical vertebrae and middle phalanx maturity, and the dental calcification within the Deutero-Malay group has been proven. Objective: To confirm the correlation between the mandible length and the dental calcification. Methods: This was an observational research with a cross-sectional design, done on 160 Deutero-Malay subjects, aged 8-16 years. The length of mandible was measured from Condylion to Gnathion, and the dental calcification was evaluated by Demirijan method. Results: of Spearman nonparametric correlation test indicated the significant correlation between the mandible length and canine calcification (r=0.713, the second premolar (r=0.753, and the second molar (r=0.772. The result of Multiple Classification Analysis showed that the highest correlation to the mandible length was the second molar calcification (ß=0.495.DOI: 10.14693/jdi.v17i1.107

  5. Exposure to Persistent Organic Pollutants Predicts Telomere Length in Older Age: Results from the Helsinki Birth Cohort Study

    Science.gov (United States)

    Guzzardi, Maria Angela; Iozzo, Patricia; Salonen, Minna K.; Kajantie, Eero; Airaksinen, Riikka; Kiviranta, Hannu; Rantakokko, Panu; Eriksson, Johan Gunnar

    2016-01-01

    As the population ages, the occurrence of chronic pathologies becomes more common. Leukocyte telomere shortening associates to ageing and age-related diseases. Recent studies suggest that environmental chemicals can affect telomere length. Persistent organic pollutants (POPs) are most relevant, since they are ingested with foods, and accumulate in the body for a long time. This longitudinal study was undertaken to test if circulating POPs predict telomere length and shortening in elderly people. We studied 1082 subjects belonging to the Helsinki Birth Cohort Study (born 1934-1944), undergoing two visits (2001-2004 and 2011-2014). POPs (oxychlordane, trans-nonachlor, p, p’-DDE, PCB 153, BDE 47, BDE 153) were analysed at baseline. Relative telomere length was measured twice, ’10 years apart, by quantitative real-time PCR. Oxychlordane, trans-nonachlor and PCB-153 levels were significant predictors of telomere length and shortening. In men, we did not find a linear relationship between POPs exposure and telomere shortening. In women, a significant reduction across quartiles categories of oxychlordane and trans-nonachlor exposure was observed. Baseline characteristics of subjects in the highest POPs categories included higher levels of C-reactive protein and fasting glucose, and lower body fat percentage. This is one of few studies combining POPs and telomere length. Our results indicate that exposure to oxychlordane, trans-nonachlor and PCB 153 predicts telomere attrition. This finding is important because concentrations of POPs observed here occur in contemporary younger people, and may contribute to an accelerated ageing. PMID:27699078

  6. Cognitive and neuroinflammatory consequences of mild repeated stress are exacerbated in aged mice

    Science.gov (United States)

    Buchanan, J.B.; Sparkman, N.L.; Chen, J.; Johnson, R.W.

    2008-01-01

    Summary Peripheral immune stimulation as well as certain types of psychological stress increases brain levels of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNFα). We have demonstrated that aged mice show greater increases in central inflammatory cytokines, as well as greater cognitive deficits, compared to adults in response to peripheral lipopolysaccharide (LPS) administration. Because aged mice are typically more sensitive to systemic stressors such as LPS, and certain psychological stressors induce physiological responses similar to those that follow LPS, we hypothesized that aged mice would be more sensitive to the physiological and cognitive effects of mild stress than adult mice. Here, adult (3–5 mo) and aged (22–23 mo) male BALB/c mice were trained in the Morris water maze for 5 days. Mice were then exposed to a mild restraint stress of 30 minutes before being tested in a working memory version of the water maze over a 3 day period. On day 4 mice were stressed and then killed for collection of blood and brain. In a separate group of animals, mice were killed immediately after one, two or three 30 min restraint sessions and blood for peripheral corticosterone and cytokine protein measurement, and brains were dissected for central cytokine mRNA measurement. Stress disrupted spatial working memory in both adult and aged mice but to a much greater extent in the aged mice. In addition, aged mice showed an increase in stress-induced expression of hippocampal IL-1β mRNA and MHC class II protein compared to non-stressed controls while expression in adult mice was unaffected by stress. These data show that aged mice are more sensitive to both the cognitive and inflammatory effects of mild stress than are adult mice and suggest a possible a role for IL-1β. PMID:18407425

  7. A method for estimating age of medieval sub-adults from infancy to adulthood based on long bone length.

    Science.gov (United States)

    Primeau, Charlotte; Friis, Laila; Sejrsen, Birgitte; Lynnerup, Niels

    2016-01-01

    To develop a series of regression equations for estimating age from length of long bones for archaeological sub-adults when aging from dental development cannot be performed. Further, to compare derived ages when using these regression equations, and two other methods. A total of 183 skeletal sub-adults from the Danish medieval period, were aged from radiographic images. Linear regression formulae were then produced for individual bones. Age was then estimated from the femur length using three different methods: equations developed in this study, data based on a modern population (Maresh: Human growth and development (1970) pp 155-200), and, lastly, based on archeological data with known ages (Rissech et al.: Forensic Sci Int 180 (2008) 1-9). As growth of long bones is known to be non-linear it was tested if the regression model could be improved by applying a quadratic model. Comparison between estimated ages revealed that the modern data result in lower estimated ages when compared to the Danish regression equations. The estimated ages using the Danish regression equations and the regression equations developed by Rissech et al. (Forensic Sci Int 180 (2007) 1-9) were very similar, if not identical. This indicates that the growth between the two archaeological populations is not that dissimilar. This would suggest that the regression equations developed in this study may potentially be applied to archaeological material outside Denmark as well as later than the medieval period, although this would require further testing. The quadratic equations are suggested to yield more accurate ages then using simply linear regression equations. © 2015 Wiley Periodicals, Inc.

  8. Repeat length variation in the 5'UTR of myo-inositol monophosphatase gene is related to phytic acid content and contributes to drought tolerance in chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Joshi-Saha, Archana; Reddy, Kandali S

    2015-09-01

    Myo-inositol metabolism plays a significant role in plant growth and development, and is also used as a precursor for many important metabolites, such as ascorbate, pinitol, and phytate. Phytate (inositol hexakisphosphate) is the major storage pool for phosphate in the seeds. It is utilized during seed germination and growth of the developing embryo. In addition, it is implicated in protection against oxidative stress. In the present study, a panel of chickpea accessions was used for an association analysis. Association analysis accounting for population structure and relative kinship identified alleles of a simple sequence repeat marker, NCPGR90, that are associated with both phytic acid content and drought tolerance. These alleles varied with respect to the dinucleotide CT repeats present within the marker. NCPGR90 located to the 5'UTR of chickpea myo-inositol monophosphatase gene (CaIMP) and showed transcript length variation in drought-tolerant and drought-susceptible accessions. CaIMP from a drought-tolerant accession with a smaller repeat was almost 2-fold upregulated as compared to a susceptible accession having a longer repeat, even under control non-stressed conditions. This study suggests an evolution of simple sequence repeat length variation in CaIMP, which might be regulating phytic acid levels to confer drought tolerance in natural populations of chickpea.

  9. Cytogenetic and molecular analysis of the Y chromosome: absence of a significant relationship between CAG repeat length in exon 1 of the androgen receptor gene and infertility in Indian men.

    Science.gov (United States)

    Dhillon, Varinderpal S; Husain, Syed A

    2003-10-01

    The genetic basis of male infertility remains unclear in the majority of cases. Recent studies have indicated an association between microdeletions of the azoospermia factor a (AZFa)-AZFc regions of Yq and severe oligospermia or azoospermia. Increased (CAG)n repeat lengths in the androgen receptor (AR) gene have also been reported in infertile men. Therefore, in order to assess the prevalence of these genetic defects to male infertility, 183 men with non-obstructive azoospermia (n = 70), obstructive azoospermia (n = 33), severe oligospermia (n = 80) and 59 fertile men were examined cytogenetically and at molecular level for Yq deletions, microdeletions, and AR-CAG repeat lengths along with hormonal profiles [luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T)]. We used high resolution cytogenetics to detect chromosome deletions and multiplex polymerase chain reaction (PCR) involving 27 sequence-tagged site (STS) markers on Yq to determine the rate and extent of Yq microdeletions. PCR amplification with primers flanking exon 1 of AR gene was used to determine the AR-(CAG)n repeat lengths. Hormonal profiles (LH, FSH and T levels) were also analysed in infertile and fertile men. Testicular biopsies showed Sertoli cell only (SCO) morphology, maturation arrests (MA) and hypospermatogenesis. No chromosome aberrations were found in infertile men but there was a significant increase (p CAG repeats in AR gene was observed between infertile and fertile men (22.2 +/- 1.5 and 21.5 +/- 1.4 respectively). No significant increase or decrease in levels of LH, FSH and T was observed in infertile and fertile men. In some infertile men, significantly elevated levels of FSH alone or in combination with LH were found to be indicative of failure of spermatogenesis and/or suggestive of testicular failure. Y-chromosome microdeletions contribute to infertility in some patients but no relationship could be established with the (CAG)n repeat lengths in exon 1 of

  10. Longitudinal patterns in flathead catfish relative abundance and length at age within a large river: Effects of an urban gradient

    Science.gov (United States)

    Paukert, C.P.; Makinster, A.S.

    2009-01-01

    We investigated the spatial variation of flathead catfish (Pylodictis olivaris) relative abundance and growth in the 274 km long Kansas River to determine if population dynamics of catfish are related to urbanization. Electrofishing was conducted at 462 random sites throughout the river in summer, 2005-2006 to collect fish. Relative abundance of age 1 fish (???200mm), subadult (>200-400mm) and adult fish (>400 mm) ranged from 0.34 to 14.67 fish h-1, mean length at age 1 was 165 (range: 128-195) mm total length (TL) and mean length at age 3 was 376 mm TL (range: 293-419mm TL). The proportion of land use within 200 m of the river edge was between 0 and 0.54 urban. River reaches with high relative abundance of age 1 flathead catfish had high relative abundance of subadult and adult catfish. River reaches with fast flathead catfish growth to age 1 had fast growth to age 3. High urban land use and riprap in the riparian area were evident in river reaches near the heavily populated Kansas City and Topeka, Kansas, USA. Reaches with increased number of log jams and islands had decreased riparian agriculture. Areas of low urbanization had faster flathead catfish growth (r = 0.67, p = 0.005). Relative abundance of flathead catfish was higher in more agricultural areas (r = -0.57, p = 0.02). Changes in land use in riverine environments may alter population dynamics of a fish species within a river. Spatial differences in population dynamics need to be considered when evaluating riverine fish populations. Published in 2008 by John Wiley & Sons Ltd.

  11. Relative Leukocyte Telomere Length, Hematological Parameters and Anemia - Data from the Berlin Aging Study II (BASE-II).

    Science.gov (United States)

    Meyer, Antje; Salewsky, Bastian; Buchmann, Nikolaus; Steinhagen-Thiessen, Elisabeth; Demuth, Ilja

    2016-01-01

    The length of the chromosome ends, telomeres, is widely accepted as a biomarker of aging. However, the dynamic of the relationship between telomere length and hematopoietic parameters in the normal aging process, which is of particular interest with respect to age-related anemia, is not well understood. We have analyzed the relationship between relative leukocyte telomere length (rLTL) and several hematological parameters in the older group of the Berlin Aging Study II (BASE-II) participants. This paper also compares rLTL between both BASE-II age groups (22-37 and 60-83 years). Genomic DNA was extracted from peripheral blood leukocytes of BASE-II participants and used to determine rLTL by a quantitative PCR protocol. Standard methods were used to determine blood parameters, and the WHO criteria were used to identify anemic participants. Telomere length data were available for 444 younger participants (28.4 ± 3.1 years old; 52% women) and 1,460 older participants (68.2 ± 3.7 years old; 49.4% women). rLTL was significantly shorter in BASE-II participants of the older group (p = 3.7 × 10-12) and in women (p = 4.2 × 10-31). rLTL of older men exhibited a statistically significant, positive partial correlation with mean corpuscular hemoglobin (MCH; p = 0.012) and MCH concentration (p = 0.002). While these correlations were only observed in men, the rLTL of older women was negatively correlated with the number of thrombocytes (p = 0.015) in the same type of analysis. Among all older participants, 6% met the criteria to be categorized as 'anemic'; however, there was no association between anemia and rLTL. In the present study, we have detected isolated correlations between rLTL and hematological parameters; however, in all cases, rLTL explained only a small part of the variation of the analyzed parameters. In disagreement with some other studies showing similar data, we interpret the association between rLTL and some of the hematological parameters studied here to be

  12. Age-dependence of relative telomere length profiles during spermatogenesis in man

    DEFF Research Database (Denmark)

    Jørgensen, Pernille Bach; Fedder, Jens; Koelvraa, Steen

    2013-01-01

    human spermatogenesis. A few groups have tried to elucidate this process by measuring telomerase activity in the various cell-types during spermatogenesis, but until now, no one has ever measured telomere length (TL) during these different stages in humans. Some groups have measured TL in spermatozoa...... by telomere QFISH. Our data revealed no difference in the TL profile during spermatogenesis between younger and older men. All men had a similar profile which strongly resembled the telomerase expression profile found by others. This indicates that the longer telomeres in older men are not caused by a wider...... window of telomere elongation, stretching over more cell-types of spermatogenesis....

  13. Non-linear association between androgen receptor CAG and GGN repeat lengths and reproductive parameters in fertile European and Inuit men

    DEFF Research Database (Denmark)

    Brokken, L J S; Rylander, L; Jönsson, B A

    2013-01-01

    . A linear association was only found between sperm DNA fragmentation index (DFI) and CAG length, and between inhibin B and GGN length. Men with longer CAG then the reference (22-24), had higher oestradiol levels, whereas men with shorter CAG stretches had a higher DFI and a higher proportion of Fas...

  14. Longitudinal decline of leukocyte telomere length in old age and the association with sex and genetic risk.

    Science.gov (United States)

    Berglund, Kari; Reynolds, Chandra A; Ploner, Alexander; Gerritsen, Lotte; Hovatta, Iiris; Pedersen, Nancy L; Hägg, Sara

    2016-07-01

    Telomeres are DNA-protein structures at the ends of chromosomes. Leukocyte telomere length (LTL) shortening has been associated with advanced age. However, most studies use cross-sectional data, hence, the aim of our study was to model longitudinal trajectories of LTL attrition across 20 years at old age. Assessments of LTL were done by qPCR in SATSA (Swedish Adoption/Twin Study of Aging; N=636 individuals). Cross-sectional and longitudinal associations with age were estimated, the latter using latent growth curve analysis. A genetic risk score (GRS) for LTL was further assessed and included in the models. We confirmed an inverse cross-sectional association of LTL with age (B=-0.0022 T/S-ratio; 95% CI: -0.0035, -0.0009, p-value=0.0008). Longitudinal LTL analyses adjusted for sex (1598 samples; ≤5 measurements) suggested modest average decline until 69 years of age but accelerating decline after 69 years, with significant inter-individual variation. Women had on average ~6% T/S-ratio units longer LTL at baseline, and inclusion of the GRS improved the model where four risk alleles was equivalent to the effect size difference between the sexes. In this cohort of old individuals, baseline LTL varied with age, sex and genetic background. The rate of change of LTL accelerated with age and varied considerably between individuals.

  15. Serum 25-Hydroxyvitamin D Has a Modest Positive Association with Leukocyte Telomere Length in Middle-Aged US Adults.

    Science.gov (United States)

    Beilfuss, Julia; Camargo, Carlos A; Kamycheva, Elena

    2017-04-01

    Background: Vitamin D deficiency has been linked to all-cause mortality and cancer. However, the biological plausibility of these associations is not well established. Leukocyte telomere length (LTL) shortening is associated with aging and is a hallmark of genomic instability and carcinogenesis.Objective: We aimed to investigate the association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and LTL in the general US population.Methods: We analyzed data from the US NHANES 2001-2002. The study population comprised 1542 younger adults (aged 20-39 y), 1336 middle-aged adults (aged 40-59 y), and 1382 older adults (aged ≥60 y). LTL was measured by using quantitative polymerase chain reaction. Serum 25(OH)D concentrations ≥50 nmol/L were considered optimal. Linear regression, adjusted for age, sex, race/ethnicity, body mass index (BMI), total energy and sugar intakes, calcium intake, socioeconomic status, milk and dietary supplement consumption, and physical activity, was applied to investigate the association between serum 25(OH)D and LTL.Results: In the total population, age, sex, BMI, and non-Hispanic black race/ethnicity were significant predictors of LTL. In the participants aged 40-59 y, an increment in serum 25(OH)D of 10 nmol/L was associated with a 0.03- ± 0.01-kbp longer LTL, adjusted for age, sex, race/ethnicity, and other factors (P = 0.001). In the same age group, 25(OH)D concentrations ≥50 nmol/L were associated with a 0.13- ± 0.04-kbp longer LTL than those for 25(OH)D concentrations D was positively associated with LTL in middle-aged participants (aged 40-59 y), independently of other factors. These findings suggest that decreased 25(OH)D concentrations are associated with genomic instability, although the clinical impact of this observation remains unclear.

  16. Case study: videogame distraction reduces behavioral distress in a preschool-aged child undergoing repeated burn dressing changes: a single-subject design

    National Research Council Canada - National Science Library

    Sil, Soumitri; Dahlquist, Lynnda M; Burns, Andrew J

    2013-01-01

    This single-subject design study evaluated the feasibility and efficacy of passive and interactive videogame distraction on behavioral distress for a preschool-aged child receiving repeated burn dressing changes...

  17. College Students' Chronological Age Predicts Marital Happiness Regardless of Length of Marriage

    Science.gov (United States)

    Weinstein, Lawrence; Powers, Justina; Laverghetta, Antonio

    2010-01-01

    A revised version of the Quality Marriage Index (QMI) was used to examine demographic correlates of marital satisfaction. We administered the revised QMI to a sample of college students and found a significant positive correlation between age and relationship satisfaction. We suggest that this increase in relationship satisfaction could be due to…

  18. Telomeric repeat factor 1 protein levels correlates with telomere length in colorectal cancer Los niveles proteicos del factor de repetición telomérico 1 se correlacionan con la longitud del telómero en el cáncer colorrectal

    Directory of Open Access Journals (Sweden)

    Cristina Valls-Bautista

    2012-11-01

    Full Text Available Background: colorectal cancer is the third cancer cause of death in Spain. It is important to investigate new tumoral markers for early diagnosis, disease monitoring and prevention strategies. Telomeres protect the chromosome from degradation by nucleases and end-to-end fusion. The progressive loss of the telomeric ends of chromosomes is an important mechanism in the timing of human cellular aging. Telomeric Repeat Factor 1 (TRF1 is a protein that binds at telomere ends. Purpose: to measure the concentrations of TRF1 and the relationships among telomere length, telomerase activity, and TRF1 levels in tumor and normal colorectal mucosa. Method: from normal and tumoral samples of 83 patients who underwent surgery for colorectal cancer we analyzed TRF1 protein concentration by Western Blot, telomerase activity, by the fluorescent-telomeric repeat amplification protocol assay and telomere length by Southern Blot. Results: high levels of TRF1 were observed in 68.7% of tumor samples, while the majority of normal samples (59% showed negative or weak TRF1 concentrations. Among the tumor samples, telomere length was significantly associated with TRF1 protein levels (p = 0.023. Conclusions: a relationship was found between telomere length and TRF1 abundance protein in tumor samples, which means that TRF1 is an important factor in the tumor progression and maybe a diagnostic factor.

  19. Study of the relationship between non-dimensional roughness length and wave age, effected by wave directionality

    Indian Academy of Sciences (India)

    Naoya Suzuki; Naoto Ebuchi; Chaofang Zhao; Isao Watabe; Yasuhiro Sugimori

    2002-09-01

    Relationship between the non-dimensional roughness length and inverse of wave age has been discussed without consideration of wave directions, though wind wave field consists of various directional component waves. In this study we observe wave heights by an array of four wave gauges at the Hiratsuka Tower of (Independent Administrative Institution) National Research Institute for Earth Science and Disaster Prevention (NIED), Japan, and discuss the effect of wave directionality. As a result, the data sets were classified into two different groups according to the directional wave spectrum distribution. In case 1 only swell and wind waves exist and in case 2 there exist wave components from several directions. It is shown that the case of multiple- directional component waves (case 2) may affect the non-dimensional roughness length and friction velocity.

  20. Social Relationships and Salivary Telomere Length Among Middle-Aged and Older African American and White Adults.

    Science.gov (United States)

    Lincoln, Karen D; Lloyd, Donald A; Nguyen, Ann W

    2017-05-09

    A common mechanism underlying premature morbidity may be accelerated biological aging as reflected by salivary telomere length (STL). This study examined the extent to which social relationships, both positive and negative, can be protective or confer risk relative to biological aging. Data from the Health and Retirement Study and multiple regression were used to examine cross-sectional associations between STL, self-reported social support, and negative interaction (e.g., conflict, criticism) with family in a nationally representative sample of African American and non-Hispanic White middle-aged and older adults (N = 4,080). Social support from family was associated with shorter STL. Negative interaction with family had no main effect on STL but interactions characterized by high social support and more frequent negative interactions were associated with longer STL. Negative interaction with family was negatively associated with STL for African Americans and Whites but the magnitude of the effect was greater for African Americans. Study findings highlight the role of social relationships in physiological deterioration among middle-aged and older adults and identify a potential mechanism whereby race is linked to accelerated biological aging. Findings highlight the importance of considering positive and negative aspects of social relationships to understand the consequences of social connections for cellular aging in diverse populations.

  1. The Brief Repeatable Battery: psychometrics and normative values with age, education and gender corrections in a Serbian population.

    Science.gov (United States)

    Obradovic, D; Petrovic, M; Antanasijevic, I; Marinkovic, J; Stojanovic, T; Obradovic, S

    2012-12-01

    Cognitive impairment is present in up to 65 % of multiple sclerosis (MS) patients. The Brief Repeatable Battery of neuropsychological tests (BRB) is one of the most used neuropsychological tools for cognitive assessment in MS. However, relative lack of normative data limits its application in research and clinical practice. In order to obtain normative data for a Serbian population, we administered the BRB version A to 140 healthy subjects and assessed the influence of demographic factors such as gender, age, and education on the tests' scores. We also calculated corrections for these factors. Higher education was associated with better performance on all the tests. Age influenced all the tests, except the word list generation, higher age being associated with worse performance on all other tests. Women performed worse on the paced auditory serial addition test 2, no other gender differences were observed. Our data obtained for the Serbian population could further improve use of the BRB in clinical practice and for the research purposes, establishing cognitive evaluation as a part of standard neurological examination of MS patients.

  2. Weight, Length, and Body Mass Index Growth of Children Under 2 Years of Age With Cleft Lip and Palate.

    Science.gov (United States)

    Miranda, Gabriela Serrano; Marques, Ilza Lazarini; de Barros, Suely Prietto; Arena, Eliane Petean; de Souza, Luiz

    2016-05-01

    To study the growth of length-for-age (L/A), weight-for-age (W/A), and body mass index (BMI) of children with cleft lip and palate receiving a normal diet; to establish specific growth curves for children with cleft palate with or without cleft lip (CLP/ICP) who had not undergone palatoplasty and for children with isolated cleft lip (ICL); and to assess if CLP/ICP growth differed from ICL growth and if CLP/ICP and ICL growth differed from growth for typical children. Prospective and cross-sectional study. Hospital for Rehabilitation of Craniofacial Anomalies, Bauru, São Paulo, Brazil. Weight and length of 381 children with cleft lip and palate and who were younger than 2 years were recorded and used to calculate W/A, L/A, and BMI growth curves. The 2006 World Health Organization growth charts were used as a reference for typical children. All children received a normal diet for age. Children with CLP/ICP had median W/A and BMI growth curves below growth curves for typical children but showed spontaneous recovery starting at approximately 5 months of age, even with nonoperated cleft palate. Children with ICL had growth similar to that of typical children. Children with CLP/ICP, who initially had W/A and BMI values less than those of the ICL group, had W/A and BMI equal to or higher than the ICL group after 9 months of age. Children with CLP/ICP had impaired W/A and BMI growth with spontaneous recovery starting early in childhood. This study established specific W/A, BMI, and L/A growth curves for children with cleft lip and palate.

  3. A variable number of tandem repeats in the 3'-untranslated region of the dopamine transporter modulates striatal function during working memory updating across the adult age span.

    Science.gov (United States)

    Sambataro, Fabio; Podell, Jamie E; Murty, Vishnu P; Das, Saumitra; Kolachana, Bhaskar; Goldberg, Terry E; Weinberger, Daniel R; Mattay, Venkata S

    2015-08-01

    Dopamine modulation of striatal function is critical for executive functions such as working memory (WM) updating. The dopamine transporter (DAT) regulates striatal dopamine signaling via synaptic reuptake. A variable number of tandem repeats in the 3'-untranslated region of SLC6A3 (DAT1-3'-UTR-VNTR) is associated with DAT expression, such that 9-repeat allele carriers tend to express lower levels (associated with higher extracellular dopamine concentrations) than 10-repeat homozygotes. Aging is also associated with decline of the dopamine system. The goal of the present study was to investigate the effects of aging and DAT1-3'-UTR-VNTR on the neural activity and functional connectivity of the striatum during WM updating. Our results showed both an age-related decrease in striatal activity and an effect of DAT1-3'-UTR-VNTR. Ten-repeat homozygotes showed reduced striatal activity and increased striatal-hippocampal connectivity during WM updating relative to the 9-repeat carriers. There was no age by DAT1-3'-UTR-VNTR interaction. These results suggest that, whereas striatal function during WM updating is modulated by both age and genetically determined DAT levels, the rate of the age-related decline in striatal function is similar across both DAT1-3'-UTR-VNTR genotype groups. They further suggest that, because of the baseline difference in striatal function based on DAT1-3'-UTR-VNTR polymorphism, 10-repeat homozygotes, who have lower levels of striatal function throughout the adult life span, may reach a threshold of decreased striatal function and manifest impairments in cognitive processes mediated by the striatum earlier in life than the 9-repeat carriers. Our data suggest that age and DAT1-3'-UTR-VNTR polymorphism independently modulate striatal function. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  4. Comparative genotyping of Campylobacter jejuni by amplified fragment length polymorphism, multilocus sequence typing, and short repeat sequencing: Strain diversity, host range, and recombination

    NARCIS (Netherlands)

    Schouls, L.M.; Reulen, S.; Duim, B.; Wagenaar, J.A.; Willems, R.J.L.; Dingle, K.E.; Colles, F.M.; Embden, van J.D.A.

    2003-01-01

    Three molecular typing methods were used to study the relationships among 184 Campylobacter strains isolated from humans, cattle, and chickens. All strains were genotyped by amplified fragment length polymorphism (AFLP) analysis, multilocus sequence typing (MLST), and sequence analysis of a genomic

  5. The Repeated Computation of the Bond Length and Ground- State Energy for H2 +%H2+键长和基态能量的再计算

    Institute of Scientific and Technical Information of China (English)

    李旭; 胡先权

    2002-01-01

    Ritz variation method was used to find the numerical relation bctween the energy near the ground - state of the hydrogenmolecular ion H2 + .and the changes of the variation parameter andthe bond length, the computation formula of bond length and ground- state energy for H2 * was also obtained by means of the method ofparabolie interpolation. The computation results were much closer toexperinental values than those of Refs. [ 1,2]' s.%用Ritz变分法求出了氢分子离子H2+基态能量附近的能量随变分参数和分子键长变化的数值关系,并用抛物线插值法获得了H2+键长和基态能量的值及其计算公式,比文献[1,2]更接近于实验值.

  6. Assessment of Telomere Length in Archived Formalin-Fixed, Paraffinized Human Tissue Is Confounded by Chronological Age and Storage Duration

    Science.gov (United States)

    2016-01-01

    Telomeres shorten with physiological aging but undergo substantial restoration during cancer immortalization. Increasingly, cancer studies utilize the archive of formalin-fixed, paraffin-embedded (FFPE) tissues in diagnostic pathology departments. Conceptually, such studies would be confounded by physiological telomere attrition and loss of DNA integrity from prolonged tissue storage. Our study aimed to investigate these two confounding factors. 145 FFPE tissues of surgically-resected, non-diseased appendixes were retrieved from our pathology archive, from years 2008 to 2014. Cases from 2013 to 2014 were categorized by patient chronological age (0–20 years, 21–40 years, 41–60 years, > 60 years). Telomere lengths of age categories were depicted by telomere/chromosome 2 centromere intensity ratio (TCR) revealed by quantitative fluorescence in situ hybridization. Material from individuals aged 0–20 years from years 2013/2014, 2011/2012, 2009/2010, and 2008 were compared for storage effect. Telomere integrity was assessed by telomere fluorescence intensity (TFI). Epithelial TCRs (mean ± SD) for the respective age groups were 4.84 ± 2.08, 3.64 ± 1.21, 2.03 ± 0.37, and 1.93 ± 0.45, whereas corresponding stromal TCRs were 5.16 ± 2.55, 3.84 ± 1.36, 2.49 ± 1.20, and 2.93 ± 1.24. A trend of inverse correlation with age in both epithelial and stromal tissues is supported by r = -0.69, p archived beyond 2 years are suboptimal for telomere analysis. PMID:27598341

  7. The 28S-18S rDNA intergenic spacer from Crithidia fasciculata: repeated sequences, length heterogeneity, putative processing sites and potential interactions between U3 small nucleolar RNA and the ribosomal RNA precursor.

    Science.gov (United States)

    Schnare, M N; Collings, J C; Spencer, D F; Gray, M W

    2000-09-15

    In Crithidia fasciculata, the ribosomal RNA (rRNA) gene repeats range in size from approximately 11 to 12 kb. This length heterogeneity is localized to a region of the intergenic spacer (IGS) that contains tandemly repeated copies of a 19mer sequence. The IGS also contains four copies of an approximately 55 nt repeat that has an internal inverted repeat and is also present in the IGS of Leishmania species. We have mapped the C.fasciculata transcription initiation site as well as two other reverse transcriptase stop sites that may be analogous to the A0 and A' pre-rRNA processing sites within the 5' external transcribed spacer (ETS) of other eukaryotes. Features that could influence processing at these sites include two stretches of conserved primary sequence and three secondary structure elements present in the 5' ETS. We also characterized the C.fasciculata U3 snoRNA, which has the potential for base-pairing with pre-rRNA sequences. Finally, we demonstrate that biosynthesis of large subunit rRNA in both C. fasciculata and Trypanosoma brucei involves 3'-terminal addition of three A residues that are not present in the corresponding DNA sequences.

  8. Transcription of TP0126, Treponema pallidum putative OmpW homolog, is regulated by the length of a homopolymeric guanosine repeat.

    Science.gov (United States)

    Giacani, Lorenzo; Brandt, Stephanie L; Ke, Wujian; Reid, Tara B; Molini, Barbara J; Iverson-Cabral, Stefanie; Ciccarese, Giulia; Drago, Francesco; Lukehart, Sheila A; Centurion-Lara, Arturo

    2015-06-01

    An effective mechanism for introduction of phenotypic diversity within a bacterial population exploits changes in the length of repetitive DNA elements located within gene promoters. This phenomenon, known as phase variation, causes rapid activation or silencing of gene expression and fosters bacterial adaptation to new or changing environments. Phase variation often occurs in surface-exposed proteins, and in Treponema pallidum subsp. pallidum, the syphilis agent, it was reported to affect transcription of three putative outer membrane protein (OMP)-encoding genes. When the T. pallidum subsp. pallidum Nichols strain genome was initially annotated, the TP0126 open reading frame was predicted to include a poly(G) tract and did not appear to have a predicted signal sequence that might suggest the possibility of its being an OMP. Here we show that the initial annotation was incorrect, that this poly(G) is instead located within the TP0126 promoter, and that it varies in length in vivo during experimental syphilis. Additionally, we show that TP0126 transcription is affected by changes in the poly(G) length consistent with regulation by phase variation. In silico analysis of the TP0126 open reading frame based on the experimentally identified transcriptional start site shortens this hypothetical protein by 69 amino acids, reveals a predicted cleavable signal peptide, and suggests structural homology with the OmpW family of porins. Circular dichroism of recombinant TP0126 supports structural homology to OmpW. Together with the evidence that TP0126 is fully conserved among T. pallidum subspecies and strains, these data suggest an important role for TP0126 in T. pallidum biology and syphilis pathogenesis.

  9. Estimation of gestational age from measurement of crown-rump length with transvaginal sonography in early pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hyun Ju; Lee, Young Ho; Kim, Young Hwa [Cheil General Hospital, Seoul (Korea, Republic of)

    1994-12-15

    Estimation of gestational age using crown-rump length (CRL) has been considered to be relatively accurate. The purpose of this study was to determine the relationship between the gestational age (GA) and the CRL seen ontransvaginal sonography and to improve the gestational dating creteria. One hundred and ninety five patients with known date of conception, who were pregnant between February 1990 and December 1992, were examined with high resolution transvaginal ultrasonography. There was a linear relationship between the CRL and the GA from the 27th to the 56th day of ovulation. It was defined by equation, as GA=0.97xCRL+42.4 (r=0.95, p<0.0001). Regression values with 95% confidence limit for CRL were +3.9-4.0 days. Comparison of regression lines between the data from the natural cycle group (N=53) and those from the hormonally treated group (N=142) was performed. There was no statistically significant difference between the two groups (analysis of convariance, p>0.05) In conclusion, trasvaginal sonography was useful in the determination of the GA in the early pregnancy from the 27th day of ovulation up to the 56th day. A new reference chart is provided for the estimation of gestational age according to the CRL

  10. Association of Age to Mortality and Repeat Revascularization in End-Stage Renal Disease Patients: Implications for Clinicians and Future Health Policies

    Science.gov (United States)

    Krishnaswami, Ashok; Alloggiamento, Thomas; Forman, Daniel E; Leong, Thomas K; Go, Alan S; McCulloch, Charles E

    2016-01-01

    Background: The clinical effects of age occur over an age continuum, yet age as a primary predictor is often analyzed using arbitrary age cut-points. Objective: To assess whether transformation of a continuous variable such as age using a spline function can uncover nonlinear associations between age and cardiovascular outcomes. Design: Observational retrospective cohort study in 1015 Kaiser Permanente Northern California patients with end-stage renal disease after index coronary revascularization. Age, the primary predictor, was modeled by 5 different techniques: 1) dichotomized at 65 years or older; 2) at 80 years or older (as a sensitivity analysis); 3) categorized as younger than 55 years (reference), 55 to 64, 65 to 74, and 75 years or older; 4) linear (every 5 years) variable; and 5) nonlinear by transformation into a cubic spline. Age categories were changed in a sensitivity analysis. Main Outcome Measures: Primary and secondary outcomes were all-cause mortality and repeat revascularization, respectively. Results: Graphical assessment demonstrated that age dichotomized at either 65 years and older or 80 years and older led to loss of information. Categorized age underestimated or overestimated risk at the extremes of age. A sensitivity analysis demonstrated that an arbitrary change in the age category led to a different conclusion. Age modeled linearly adequately represented mortality risk but was suboptimal with repeat revascularization. Only the cubic spline demonstrated the nonlinear association between age and repeat revascularization. Conclusion: Employing the continuous variable age as a case study, we have demonstrated that the use of flexible transformations, such as spline functions, can unearth clinically meaningful associations that would not have been possible otherwise. Future research should determine whether incorporation of these methods can improve decision making at a population level. PMID:26934624

  11. The Contributing Factors to Injury’s Length of Stay in Hospital Among Productive Age Workers in Indonesia

    Directory of Open Access Journals (Sweden)

    Lusianawaty Tana

    2016-06-01

    Full Text Available Background: Injury is one of the factors that contribute to health problems and disabilities. In Indonesia, the data oninjury and its impact are still limited and only focus on formal workers. Methods: This research aimed to describe thecharacteristics of injury by occupation and to identify factors contributed to severity (length of stay in hospital amongproductive age workers in Indonesia, using the data of National Health Research (Riskesdas in 2013. Results: We analyzed30.455 data using complex samples at 95% confi dence level. People worked as farmer, fi sherman, labor, entrepreneur,and others had more injuries in 12 months than employee (p = 0.0001. Non traffi c accident as cause of injury was alsohigher in those group of occupations than employee (p = 0.0001. The contributing factors of length of stay in hospital werethe injury with concussion (OR 23.1; 95% CI 9.2–58.1 p = 0.0001, fractures (OR 6.3; 95%CI 4.6–8.6 p = 0.0001, eyeinjury (OR 3.0; 95% CI 1.2–7.3 p = 0.0001, followed by road traffi c accident (OR 2.1; 95% CI 1.5–2.9 p = 0.0001, andinjury occurred in the business/industry/construction/farm area (OR 1.7; 95% CI 1.2–2.4 p = 0.006. Conclusion: Factorsthat contributed to the length of stay in hospital of the injury were the type of injury, cause of injury, and the area of injury.Recommendation: Efforts to overcome the injury need to be improved, especially for traffi c accidents and injury in thebusiness/industry/construction/farm area.

  12. Effect of data length and bin numbers on distribution entropy (DistEn) measurement in analyzing healthy aging.

    Science.gov (United States)

    Udhayakumar, Radhagayathri K; Karmakar, Chandan; Peng Li; Palaniswami, Marimuthu

    2015-01-01

    Complexity analysis of a given time series is executed using various measures of irregularity, the most commonly used being Approximate entropy (ApEn), Sample entropy (SampEn) and Fuzzy entropy (FuzzyEn). However, the dependence of these measures on the critical parameter of tolerance `r' leads to precarious results, owing to random selections of r. Attempts to eliminate the use of r in entropy calculations introduced a new measure of entropy namely distribution entropy (DistEn) based on the empirical probability distribution function (ePDF). DistEn completely avoids the use of a variance dependent parameter like r and replaces it by a parameter M, which corresponds to the number of bins used in the histogram to calculate it. When tested for synthetic data, M has been observed to produce a minimal effect on DistEn as compared to the effect of r on other entropy measures. Also, DistEn is said to be relatively stable with data length (N) variations, as far as synthetic data is concerned. However, these claims have not been analyzed for physiological data. Our study evaluates the effect of data length N and bin number M on the performance of DistEn using both synthetic and physiologic time series data. Synthetic logistic data of `Periodic' and `Chaotic' levels of complexity and 40 RR interval time series belonging to two groups of healthy aging population (young and elderly) have been used for the analysis. The stability and consistency of DistEn as a complexity measure as well as a classifier have been studied. Experiments prove that the parameters N and M are more influential in deciding the efficacy of DistEn performance in the case of physiologic data than synthetic data. Therefore, a generalized random selection of M for a given data length N may not always be an appropriate combination to yield good performance of DistEn for physiologic data.

  13. Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity

    Science.gov (United States)

    Kim, Sangkyu; Bi, Xiuhua; Czarny-Ratajczak, Malwina; Dai, Jianliang; Welsh, David A.; Myers, Leann; Welsch, Michael A.; Cherry, Katie E.; Arnold, Jonathan; Poon, Leonard W.

    2011-01-01

    Leukocyte telomere length is widely considered a biomarker of human age and in many studies indicative of health or disease. We have obtained quantitative estimates of telomere length from blood leukocytes in a population sample, confirming results of previous studies that telomere length significantly decreases with age. Telomere length was also positively associated with several measures of healthy aging, but this relationship was dependent on age. We screened two genes known to be involved in telomere maintenance for association with the age-related decline in telomere length observed in our population to identify candidate longevity-associated genes. A single-nucleotide polymorphism located in the SIRT1 gene and another in the 3′ flanking region of XRCC6 had significant effects on telomere length. At each bi-allelic locus, the minor variant was associated with longer telomeres, though the mode of inheritance fitting best differed between the two genes. No statistical interaction was detected for telomere length between the SIRT1 and XRCC6 variants or between these polymorphisms and age. The SIRT1 locus was significantly associated with longevity (P < 0.003). The frequency of the minor allele was higher in long-lived cases than in young controls, which coincides with the protective role of the minor variant for telomere length. In contrast, the XRCC6 variant was not associated with longevity. Furthermore, it did not affect the association of SIRT1 with exceptional survival. The association of the same variant of SIRT1 with longevity was near significant (P < 0.07) in a second population. These results suggest a potential role of SIRT1 in linking telomere length and longevity. Given the differences between this gene and XRCC6, they point to the distinct impact that alternate pathways of telomere maintenance may have on aging and exceptional survival. PMID:21972126

  14. Semen analysis in fertile patients undergoing vasectomy: reference values and variations according to age, length of sexual abstinence, seasonality, smoking habits and caffeine intake

    National Research Council Canada - National Science Library

    Bernardo Passos Sobreiro; Antonio Marmo Lucon; Fábio Firmbach Pasqualotto; Jorge Hallak; Kelly Silveira Athayde; Sami Arap

    2005-01-01

    .... The objective was to establish reference values for semen analysis and to verify the effect that age, length of sexual abstinence, seasonality, smoking habits and coffee consumption have on fertile individuals...

  15. Age-related changes in the plasticity and toughness of human cortical bone at multiple length-scales

    Energy Technology Data Exchange (ETDEWEB)

    Zimmermann, Elizabeth A.; Schaible, Eric; Bale, Hrishikesh; Barth, Holly D.; Tang, Simon Y.; Reichert, Peter; Busse, Bjoern; Alliston, Tamara; Ager III, Joel W.; Ritchie, Robert O.

    2011-08-10

    The structure of human cortical bone evolves over multiple length-scales from its basic constituents of collagen and hydroxyapatite at the nanoscale to osteonal structures at nearmillimeter dimensions, which all provide the basis for its mechanical properties. To resist fracture, bone’s toughness is derived intrinsically through plasticity (e.g., fibrillar sliding) at structural-scales typically below a micron and extrinsically (i.e., during crack growth) through mechanisms (e.g., crack deflection/bridging) generated at larger structural-scales. Biological factors such as aging lead to a markedly increased fracture risk, which is often associated with an age-related loss in bone mass (bone quantity). However, we find that age-related structural changes can significantly degrade the fracture resistance (bone quality) over multiple lengthscales. Using in situ small-/wide-angle x-ray scattering/diffraction to characterize sub-micron structural changes and synchrotron x-ray computed tomography and in situ fracture-toughness measurements in the scanning electron microscope to characterize effects at micron-scales, we show how these age-related structural changes at differing size-scales degrade both the intrinsic and extrinsic toughness of bone. Specifically, we attribute the loss in toughness to increased non-enzymatic collagen cross-linking which suppresses plasticity at nanoscale dimensions and to an increased osteonal density which limits the potency of crack-bridging mechanisms at micron-scales. The link between these processes is that the increased stiffness of the cross-linked collagen requires energy to be absorbed by “plastic” deformation at higher structural levels, which occurs by the process of microcracking.

  16. The C9orf72 repeat size correlates with onset age of disease, DNA methylation and transcriptional downregulation of the promoter.

    Science.gov (United States)

    Gijselinck, I; Van Mossevelde, S; van der Zee, J; Sieben, A; Engelborghs, S; De Bleecker, J; Ivanoiu, A; Deryck, O; Edbauer, D; Zhang, M; Heeman, B; Bäumer, V; Van den Broeck, M; Mattheijssens, M; Peeters, K; Rogaeva, E; De Jonghe, P; Cras, P; Martin, J-J; de Deyn, P P; Cruts, M; Van Broeckhoven, C

    2016-08-01

    Pathological expansion of a G4C2 repeat, located in the 5' regulatory region of C9orf72, is the most common genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). C9orf72 patients have highly variable onset ages suggesting the presence of modifying factors and/or anticipation. We studied 72 Belgian index patients with FTLD, FTLD-ALS or ALS and 61 relatives with a C9orf72 repeat expansion. We assessed the effect of G4C2 expansion size on onset age, the role of anticipation and the effect of repeat size on methylation and C9orf72 promoter activity. G4C2 expansion sizes varied in blood between 45 and over 2100 repeat units with short expansions (45-78 units) present in 5.6% of 72 index patients with an expansion. Short expansions co-segregated with disease in two families. The subject with a short expansion in blood but an indication of mosaicism in brain showed the same pathology as those with a long expansion. Further, we provided evidence for an association of G4C2 expansion size with onset age (Pdisease anticipation. Also, intermediate repeats (7-24 units) showed a slightly higher methylation degree (Pdisease mechanisms and have important implications for diagnostic counseling and potential therapeutic approaches.

  17. PolyQ repeat expansions in ATXN2 associated with ALS are CAA interrupted repeats.

    Directory of Open Access Journals (Sweden)

    Zhenming Yu

    Full Text Available Amyotrophic lateral sclerosis (ALS is a devastating, rapidly progressive disease leading to paralysis and death. Recently, intermediate length polyglutamine (polyQ repeats of 27-33 in ATAXIN-2 (ATXN2, encoding the ATXN2 protein, were found to increase risk for ALS. In ATXN2, polyQ expansions of ≥ 34, which are pure CAG repeat expansions, cause spinocerebellar ataxia type 2. However, similar length expansions that are interrupted with other codons, can present atypically with parkinsonism, suggesting that configuration of the repeat sequence plays an important role in disease manifestation in ATXN2 polyQ expansion diseases. Here we determined whether the expansions in ATXN2 associated with ALS were pure or interrupted CAG repeats, and defined single nucleotide polymorphisms (SNPs rs695871 and rs695872 in exon 1 of the gene, to assess haplotype association. We found that the expanded repeat alleles of 40 ALS patients and 9 long-repeat length controls were all interrupted, bearing 1-3 CAA codons within the CAG repeat. 21/21 expanded ALS chromosomes with 3CAA interruptions arose from one haplotype (GT, while 18/19 expanded ALS chromosomes with <3CAA interruptions arose from a different haplotype (CC. Moreover, age of disease onset was significantly earlier in patients bearing 3 interruptions vs fewer, and was distinct between haplotypes. These results indicate that CAG repeat expansions in ATXN2 associated with ALS are uniformly interrupted repeats and that the nature of the repeat sequence and haplotype, as well as length of polyQ repeat, may play a role in the neurological effect conferred by expansions in ATXN2.

  18. Age at puberty, ovulation rate, and uterine length of developing gilts fed two lysine and three metabolizable energy concentrations from 100 to 260 d of age.

    Science.gov (United States)

    Calderón Díaz, J A; Vallet, J L; Lents, C A; Nonneman, D J; Miles, J R; Wright, E C; Rempel, L A; Cushman, R A; Freking, B A; Rohrer, G A; Phillips, C; DeDecker, A; Foxcroft, G; Stalder, K

    2015-07-01

    The objective of this study was to determine the effect of ad libitum feeding diets differing in standard ileal digestible (SID) lysine and ME concentrations that bracket those fed to developing gilts in U.S. commercial settings. Average SID lysine and ME concentrations in diets currently fed to developing gilts were obtained from a poll of the U.S. commercial swine industry. Crossbred Large White × Landrace gilts (n = 1,221), housed in groups, were randomly allotted to 6 corn-soybean diets in a 2 × 3 factorial arrangement formulated to provided 2 SID lysine and 3 ME concentrations. Gilts received grower diets formulated to provide 1.02% (control = survey average) or 0.86% (control minus 15%) SID lysine and 2.94, 3.25, or 3.57 (survey average ME ± 10%) Mcal of ME/kg from 100 d of age until approximately 90 kg BW. Then, gilts were fed finisher diet containing 0.85% (control = survey average) or 0.73% (control minus 15%) SID lysine and 2.94, 3.26, or 3.59 (control ± 10%) Mcal of ME/kg until 260 d of age. Gilts were weighed, and backfat thickness and loin muscle area were recorded at the beginning of the trial and then every 28 d. Starting at 160 d of age, gilts were exposed daily to vasectomized boars and observed for behavioral estrus. At approximately 260 d of age, gilts were slaughtered and their reproductive tract was collected. Each reproductive tract was examined to determine whether the gilt was cyclic, the stage of estrus cycle, ovulation rate, and uterine length. Data were evaluated for normality and analyzed using mixed model methods. Average age at puberty was 193 d of age with a range from 160 to 265 d. When all gilts on trial at 160 d of age were included in the analysis, 91.0% reached puberty as determine by observation of standing estrus. Differences between dietary treatments on age at puberty or measurements of the reproductive tract were not detected. Growth rates to 160 d were not limiting for attainment of puberty in response to daily boar

  19. Comparison of Variable-Number Tandem-Repeat Markers typing and IS1245 Restriction Fragment Length Polymorphism fingerprinting of Mycobacterium avium subsp. hominissuis from human and porcine origins

    Directory of Open Access Journals (Sweden)

    Marttila Harri

    2010-03-01

    Full Text Available Abstract Background Animal mycobacterioses are regarded as a potential zoonotic risk and cause economical losses world wide. M. avium subsp. hominissuis is a slow-growing subspecies found in mycobacterial infected humans and pigs and therefore rapid and discriminatory typing methods are needed for epidemiological studies. The genetic similarity of M. avium subsp. hominissuis from human and porcine origins using two different typing methods have not been studied earlier. The objective of this study was to compare the IS1245 RFLP pattern and MIRU-VNTR typing to study the genetic relatedness of M. avium strains isolated from slaughter pigs and humans in Finland with regard to public health aspects. Methods A novel PCR-based genotyping method, variable number tandem repeat (VNTR typing of eight mycobacterial interspersed repetitive units (MIRUs, was evaluated for its ability to characterize Finnish Mycobacterium avium subsp. hominissuis strains isolated from pigs (n = 16 and humans (n = 13 and the results were compared with those obtained by the conventional IS1245 RFLP method. Results The MIRU-VNTR results showed a discriminatory index (DI of 0,92 and the IS1245 RFLP resulted in DI 0,98. The combined DI for both methods was 0,98. The MIRU-VNTR test has the advantages of being simple, reproducible, non-subjective, which makes it suitable for large-scale screening of M. avium strains. Conclusions Both typing methods demonstrated a high degree of similarity between the strains of human and porcine origin. The parallel application of the methods adds epidemiological value to the comparison of the strains and their origins. The present approach and results support the hypothesis that there is a common source of M. avium subsp. hominissuis infection for pigs and humans or alternatively one species may be the infective source to the other.

  20. 肯尼迪病临床特征与CAG重复序列数目关系分析%The clinical features of Kennedy disease and the correlation between clinical features and length of CAG re-peats

    Institute of Scientific and Technical Information of China (English)

    何炳接; 何若洁; 石磊; 叶城辉; 戴佳颖; 梁银杏; 卢锡林; 姚晓黎

    2015-01-01

    had family history. Clinical features included medulla oblongata and spinal muscular atrophy and weakness, limbs tremor, perioral muscles twitch and endocrine function and metabolic disorders in some cases. Creatine kinase, triglyceride, low density lipoprotein, follicle estrogen and prolactin were significantly in⁃creased compared to healthy adults (P:0.000,0.018,0.000,0.000,0.003). The number of CAG repeat was negatively correlated with the onset age (r=-0.549, P=0.001) but not associated with the illness severity (ALS rating scale) (r=0.001, P=0.998). ALS score was negatively correlated with course of disease(r=-0.540, P=0.001).Conclusions Chinese KD pa⁃ tients share similar clinical phenotypes with those of other races but exhibit slightly different clinical characteristics. The length of the CAG repeat influences age at onset but not the severity of disease. Severity of disease is related to the course of disease.

  1. Hsp72 is present in plasma from Holstein-Friesian dairy cattle, and the concentration level is repeatable across days and age classes.

    Science.gov (United States)

    Kristensen, Torsten Nygaard; Løvendahl, Peter; Berg, Peer; Loeschcke, Volker

    2004-01-01

    Although heat shock proteins (Hsps) are primarily considered as being intracellular, this study identified the presence of Hsp72 in plasma from female Holstein-Friesian dairy cattle. Plasma samples were collected from the same animals at different ages and on different days after calving and accordingly divided into 5 age classes. The age classes were calves less than 235 days of age, young heifers between 235 and 305 days of age, older heifers between 305 and 560 days of age, cows early in lactation, and cows later in lactation. For a subsample of animals within each age class, replicate plasma samples were collected from 1 to 7 days apart to test whether the Hsp72 concentration levels are repeatable on this shorter timescale. Hsp72 was observed in plasma samples from animals of all 5 age classes. For animals with blood samples taken a few days apart, the repeatability (within age class) of the Hsp72 concentration was 0.52 +/- 0.06. Age and days from calving significantly affected the Hsp72 concentration level. The highest Hsp72 level was observed in older heifers (305-560 days of age). The repeatability of Hsp72 concentrations across age classes within animal was 0.22 +/- 0.06. High environmental sensitivity and negative genetic associations between production and health traits in this high-producing breed have been documented earlier. Hsp72 is believed to be strictly stress inducible, and the finding of Hsp72 in plasma indicates that even apparently healthy individuals may experience extrinsic or intrinsic stress (or both).

  2. Rediscovery of historical Vitis vinifera varieties from the South Anatolia region by using amplified fragment length polymorphism and simple sequence repeat DNA fingerprinting methods.

    Science.gov (United States)

    Yilancioglu, Kaan; Cetiner, Selim

    2013-05-01

    Anatolia played an important role in the diversification and spread of economically important Vitis vinifera varieties. Although several biodiversity studies have been conducted with local cultivars in different regions of Anatolia, our aim is to gain a better knowledge on the biodiversity of endangered historical V. vinifera varieties in the northern Adana region of southern Anatolia, particularly those potentially displaying viticulture characteristics. We also demonstrate the genetic relatedness in a selected subset of widely cultivated and commercialized V. vinifera collection cultivars, which were obtained from the National Grapevine Germplasm located at the Institute of Viticulture, Turkey. In the present study, microsatellites were used in narrowing the sample size from 72 accessions down to a collection of 27 varieties. Amplified fragment length polymorphisms were then employed to determine genetic relatedness among this collection and local V. vinifera cultivars. The unweighted pair group method with arithmetic mean cluster and principal component analyses revealed that Saimbeyli local cultivars form a distinct group, which is distantly related to a selected subset of V. vinifera collection varieties from all over Turkey. To our knowledge, this is the first study conducted with these cultivars. Further preservation and use of these potential viticultural varieties will be helpful to avoid genetic erosion and to promote continued agriculture in the region.

  3. In situ structural characterization of ageing kinetics in aluminum alloy 2024 across angstrom-to-micrometer length scales

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Fan; Levine, Lyle E.; Allen, Andrew J.; Campbell, Carelyn E.; Creuziger, Adam A.; Kazantseva, Nataliya; Ilavsky, Jan

    2016-06-01

    The precipitate structure and precipitation kinetics in an Al-Cu-Mg alloy (AA2024) aged at 190 °C, 208 °C, and 226 °C have been studied using ex situ Transmission Electron Microscopy (TEM) and in situ synchrotron-based, combined ultra-small angle X-ray scattering, small angle X-ray scattering (SAXS), and wide angle X-ray scattering (WAXS) across a length scale from sub-Angstrom to several micrometers. TEM brings information concerning the nature, morphology, and size of the precipitates while SAXS and WAXS provide qualitative and quantitative information concerning the time-dependent size and volume fraction evolution of the precipitates at different stages of the precipitation sequence. Within the experimental time resolution, precipitation at these ageing temperatures involves dissolution of nanometer-sized small clusters and formation of the planar S phase precipitates. Using a three-parameter scattering model constructed on the basis of TEM results, we established the temperature-dependent kinetics for the cluster-dissolution and S-phase formation processes simultaneously. These two processes are shown to have different kinetic rates, with the cluster-dissolution rate approximately double the S-phase formation rate. We identified a dissolution activation energy at (149.5 ± 14.6) kJ mol-1, which translates to (1.55 ± 0.15) eV/atom, as well as an activation energy for the formation of S precipitates at (129.2 ± 5.4) kJ mol-1, i.e. (1.33 ± 0.06) eV/atom. Importantly, the SAXS/WAXS results show the absence of an intermediate Guinier-Preston Bagaryatsky 2 (GPB2)/S" phase in the samples under the experimental ageing conditions. These results are further validated by precipitation simulations that are based on Langer-Schwartz theory and a Kampmann-Wagner numerical method.

  4. AGING EFFECTS OF REPEATEDLY GLOW-DISCHARGED POLYETHYLENE - INFLUENCE ON CONTACT-ANGLE, INFRARED-ABSORPTION, ELEMENTAL SURFACE-COMPOSITION, AND SURFACE-TOPOGRAPHY

    NARCIS (Netherlands)

    VANDERMEI, HC; STOKROOS, [No Value; SCHAKENRAAD, JM; BUSSCHER, HJ

    1991-01-01

    Aging effects of repeatedly oxygen glow-discharged polyethylene surfaces were determined by water contact angle measurements, infrared (IR) spectroscopy, X-ray photoelectron (XPS) spectroscopy, and surface topography determination. Glow-discharged surfaces were stored at room temperature and in liqu

  5. English Language Learners' Nonword Repetition Performance: The Influence of Age, L2 Vocabulary Size, Length of L2 Exposure, and L1 Phonology

    Science.gov (United States)

    Duncan, Tamara Sorenson; Paradis, Johanne

    2016-01-01

    Purpose: This study examined individual differences in English language learners' (ELLs) nonword repetition (NWR) accuracy, focusing on the effects of age, English vocabulary size, length of exposure to English, and first-language (L1) phonology. Method: Participants were 75 typically developing ELLs (mean age 5;8 [years;months]) whose exposure to…

  6. Vietnamese Immigrant and Refugee Women's Mental Health: An Examination of Age of Arrival, Length of Stay, Income, and English Language Proficiency

    Science.gov (United States)

    Brown, Chris; Schale, Codi L.; Nilsson, Johanna E.

    2010-01-01

    Vietnamese immigrant and refugee women (N = 83) were surveyed regarding their mental health, English language proficiency, age of arrival, length of stay, and income. English language proficiency and age of arrival correlated with reduced symptomatology. Moreover, English language proficiency was the sole predictor of somatic distress. (Contains 1…

  7. Cumulative inflammatory load is associated with short leukocyte telomere length in the Health, Aging and Body Composition Study.

    Directory of Open Access Journals (Sweden)

    Aoife O'Donovan

    Full Text Available BACKGROUND: Leukocyte telomere length (LTL is an emerging marker of biological age. Chronic inflammatory activity is commonly proposed as a promoter of biological aging in general, and of leukocyte telomere shortening in particular. In addition, senescent cells with critically short telomeres produce pro-inflammatory factors. However, in spite of the proposed causal links between inflammatory activity and LTL, there is little clinical evidence in support of their covariation and interaction. METHODOLOGY/PRINCIPAL FINDINGS: To address this issue, we examined if individuals with high levels of the systemic inflammatory markers interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α and C-reactive protein (CRP had increased odds for short LTL. Our sample included 1,962 high-functioning adults who participated in the Health, Aging and Body Composition Study (age range: 70-79 years. Logistic regression analyses indicated that individuals with high levels of either IL-6 or TNF-α had significantly higher odds for short LTL. Furthermore, individuals with high levels of both IL-6 and TNF-α had significantly higher odds for short LTL compared with those who had neither high (OR = 0.52, CI = 0.37-0.72, only IL-6 high (OR = 0.57, CI = 0.39-0.83 or only TNF-α high (OR = 0.67, CI = 0.46-0.99, adjusting for a wide variety of established risk factors and potential confounds. In contrast, CRP was not associated with LTL. CONCLUSIONS/SIGNIFICANCE: Results suggest that cumulative inflammatory load, as indexed by the combination of high levels of IL-6 and TNF-α, is associated with increased odds for short LTL. In contrast, high levels of CRP were not accompanied by short LTL in this cohort of older adults. These data provide the first large-scale demonstration of links between inflammatory markers and LTL in an older population.

  8. Posture control development in children aged 2-7 years old, based on the changes of repeatability of the stability indices.

    Science.gov (United States)

    Sobera, Małgorzata; Siedlecka, Bożena; Syczewska, Małgorzata

    2011-03-10

    One of the most common problems encountered in posture control studies is relatively poor repeatability of postural stability measures based on the COP (center of pressure) time-series which results from the inherent variability of postural control. The repeatability of the data reflecting the postural control mechanisms in young children is still not well enough explained. The differences between of the repeatability of the stability indices of left and right foot may reflect the lateralization development of legs in the support function. The aim of the present study was two-fold: the assessment of the repeatability of the stability indices in three consecutive trials in young children, aged 2-7 years old, during quiet bipedal stance and the description of process of lower limbs lateralization, based on the difference of repeatability of both feet stability the indices changing with years. The subjects were 272 young healthy children aged 2-7 years old separated in 6 groups for children of different age. Each child stood for around 90s on two AccuSway force platforms (AMTI). The shifts of COP beneath left and right legs were recorded onto a computer by using appropriate software compatible with platforms. The indices of the ellipse area and velocity COP shifts were calculated. For assessment of the repeatability the concordance correlation coefficient (CCC) of the indices was used between the 1st and 2nd, 2nd and 3rd, and 1st and 3rd trials. Young children of 2-4 years old exhibit low level of the stability indices repeatability which increases in 5-year-old children, 6-year-olds revealed both low and high and 7-year-olds good and high levels of repeatability. Youngest children showed higher repeatability of the ellipse area of the left leg, 3- and 4-year-olds the right leg, while 6-year-olds again the left leg. In 5- and 7-year-olds there were no differences in the repeatability of stability indices between the left and right foot. The comparisons of the

  9. Effects of preincubation heating of broiler hatching eggs during storage, flock age, and length of storage period on hatchability.

    Science.gov (United States)

    Gucbilmez, M; Ozlü, S; Shiranjang, R; Elibol, O; Brake, J

    2013-12-01

    The effects of heating of eggs during storage, broiler breeder age, and length of egg storage on hatchability of fertile eggs were examined in this study. Eggs were collected from Ross 344 male × Ross 308 broiler breeders on paper flats, held overnight (1 d) at 18°C and 75% RH, and then transferred to plastic trays. In experiment 1, eggs were obtained at 28, 38, and 53 wk of flock age. During a further 10 d of storage, eggs either remained in the storage room (control) or were subjected to a heat treatment regimen of 26°C for 2 h, 37.8°C for 3 h, and 26°C for 2 h in a setter at d 5 of storage. In experiment 2, eggs from a flock at 28 wk of age were heated for 1 d of a 6-d storage period. Eggs from a 29-wk-old flock were either heated at d 1 or 5 of an 11-d storage period in experiment 3. In experiment 4, 27-wk-old flock eggs were heated twice at d 1 and 5 of an 11-d storage period. Control eggs stored for 6 or 11 d were coincubated as appropriate in each experiment. Heating eggs at d 5 of an 11-d storage period increased hatchability in experiment 1. Although no benefit of heating 28-wk-old flock eggs during 6 d of storage in experiment 2 was observed, heating eggs from a 29-wk-old flock at d 1 or 5 of an 11-d storage period increased hatchability in experiment 3. Further, heating eggs from a 27-wk-old flock twice during 11 d of storage increased hatchability in experiment 4. These effects were probably due to the fact that eggs from younger flocks had been reported to have many embryos at a stage of development where the hypoblast had not yet fully developed (less than EG-K12 to EG-K13), such that heating during extended storage advanced these embryos to a more resistant stage.

  10. Pre- and postovulatory aging of murine oocytes affect the transcript level and poly(A tail length of maternal effect genes.

    Directory of Open Access Journals (Sweden)

    Debora Dankert

    Full Text Available Maternal effect genes code for oocyte proteins that are important for early embryogenesis. Transcription in oocytes does not take place from the onset of meiotic progression until zygotic genome activation. During this period, protein levels are regulated posttranscriptionally, for example by poly(A tail length. Posttranscriptional regulation may be impaired in preovulatory and postovulatory aged oocytes, caused by delayed ovulation or delayed fertilization, respectively, and may lead to developmental defects. We investigated transcript levels and poly(A tail length of ten maternal effect genes in in vivo- and in vitro- (follicle culture grown oocytes after pre- and postovulatory aging. Quantitative RT-PCR was performed using random hexamer-primed cDNA to determine total transcript levels and oligo(dT16-primed cDNA to analyze poly(A tail length. Transcript levels of in vivo preovulatory-aged oocytes remained stable except for decreases in Brg1 and Tet3. Most genes investigated showed a tendency towards increased poly(A content. Polyadenylation of in vitro preovulatory-aged oocytes was also increased, along with transcript level declines of Trim28, Nlrp2, Nlrp14 and Zar1. In contrast to preovulatory aging, postovulatory aging of in vivo- and in vitro-grown oocytes led to a shortening of poly(A tails. Postovulatory aging of in vivo-grown oocytes resulted in deadenylation of Nlrp5 after 12 h, and deadenylation of 4 further genes (Tet3, Trim28, Dnmt1, Oct4 after 24 h. Similarly, transcripts of in vitro-grown oocytes were deadenylated after 12 h of postovulatory aging (Tet3, Trim28, Zfp57, Dnmt1, Nlrp5, Zar1. This impact of aging on poly(A tail length may affect the timed translation of maternal effect gene transcripts and thereby contribute to developmental defects.

  11. The Effect of Age and Initial Central Retinal Thickness on Earlier Need of Repeat Ozurdex Treatment for Macular Edema Due to Retinal Vein Occlusion: A Retrospective Case Series.

    Science.gov (United States)

    Lin, Chun-Ju; Chen, Huan-Sheng; Su, Cheng-Wen; Tien, Peng-Tai; Lin, Jane-Ming; Chen, Wen-Lu; Kuo, Chung-Yuan; Lai, Chun-Ting; Tsai, Yi-Yu

    2017-09-26

    To evaluate the effects of dexamethasone intravitreal implant (Ozurdex) and identify risk factors for repeated treatment in patients with macula edema due to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Patients followed up for at least 6 months were enrolled from 2013 to 2016. Dexamethasone intravitreal implant was given as the baseline treatment. For evaluation of dexamethasone intravitreal implant effects and complications, the demographics, medical history, best-corrected visual acuity (BCVA), intraocular pressure, and central retinal thickness (CRT) were recorded. Multivariate Cox proportional hazard model and logistic regression were used to identify factors for repeated treatment. Twenty-three BRVO and 11 CRVO patients were enrolled. There were 15 males and 19 females. Fifteen (44.12%) patients needed only one dexamethasone intravitreal implant. The peak CRT and BCVA significantly improved. Comparing single-injection with multiple-injection group, age and initial CRT more than 400 μm were significantly higher in the multiple-injection group. From multivariate logistic regression and Cox proportional hazards analysis, patients with age older than 55 years and initial CRT more than 400 μm had higher risk for multiple injections. Patients receiving as-needed schedule of dexamethasone intravitreal implant had significant peak CRT and BCVA improvement. Age older than 55 years and initial CRT more than 400 μm were significant risk factors associated with repeated dexamethasone intravitreal implant treatment.

  12. Alberta original the first to produce 40-foot pipe lengths : slurry pipeline production enters age of robotics

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1999-07-01

    The Resources Letter conducted an interview with an Alberta original, Doug Golosky, regarding his latest innovation, a computerized welding machine that can weld 40-foot pipe length. The welder started his own company, Clearwater Welding, in 1984 and has since worked extensively for both Syncrude and Suncor. Since 1998 Clearwater Welding has collaborated with Matrix Wear Technologies Inc. to respond to the need for an improved pipeline product, particularly in the maintenance of chromium carbide overlaid piping which is commonly used for oil sand pipelines. Golosky, together with a mechanical engineer, designed a robotic, computerized machine that can weld 40 foot length chromium carbide pipes. Only one other company can produce 40-foot length pipes, and they are in the United States. The welder has been so successful that they are looking into the prospect of welding 80-foot pipe lengths. Because the system is computerized, it has proven to be very cost efficient. 1 fig.

  13. Effects of Culture, Age, Gender, and Repeated Trials on Rote Song Learning Skills of Children 6-9 Years Old from England, Panama, Poland, Spain, and the United States.

    Science.gov (United States)

    Moore, Randall S.; Brotons, Melissa; Fyk, Janina; Castillo, Argelis

    1997-01-01

    Examines the effect of repeated trials on children aged six to nine from different countries learning a new song. States that: (1) culture influences responses; (2) rote singing improves with age; (3) girls responses are better; and (4) children repeat rhythms more accurately before they can pitch match melodic contours and precise pitches. (CMK)

  14. Age of dam and sex of calf adjustments and genetic parameters for gestation length in Charolais cattle.

    Science.gov (United States)

    Crews, D H

    2006-01-01

    To estimate adjustment factors and genetic parameters for gestation length (GES), AI and calving date records (n = 40,356) were extracted from the Canadian Charolais Association field database. The average time from AI to calving date was 285.2 d (SD = 4.49 d) and ranged from 274 to 296 d. Fixed effects were sex of calf, age of dam (2, 3, 4, 5 to 10, > or = 11 yr), and gestation contemporary group (year of birth x herd of origin). Variance components were estimated using REML and 4 animal models (n = 84,332) containing from 0 to 3 random maternal effects. Model 1 (M1) contained only direct genetic effects. Model 2 (M2) was G1 plus maternal genetic effects with the direct x maternal genetic covariance constrained to zero, and model 3 (M3) was G2 without the covariance constraint. Model 4 (M4) extended G3 to include a random maternal permanent environmental effect. Direct heritability estimates were high and similar among all models (0.61 to 0.64), and maternal heritability estimates were low, ranging from 0.01 (M2) to 0.09 (M3). Likelihood ratio tests and parameter estimates suggested that M4 was the most appropriate (P or = 11-yr-old cows, respectively. Bivariate animal models were used to estimate genetic parameters for GES with birth and adjusted 205-d weaning weights, and postweaning gain. Direct GES was positively correlated with direct birth weight (BWT; 0.34 +/- 0.04) but negatively correlated with maternal BWT (-0.20 +/- 0.07). Maternal GES had a low, negative genetic correlation with direct BWT (-0.15 +/- 0.05) but a high and positive genetic correlation with maternal BWT (0.62 +/- 0.07). Generally, GES had near-zero genetic correlations with direct and maternal weaning weights. Results suggest that important genetic associations exist for GES with BWT, but genetic correlations with weaning weight and postweaning gain were less important.

  15. Review of Telomere Length for Forensic Age Estimation%测定端粒长度推断法医学年龄的研究进展

    Institute of Scientific and Technical Information of China (English)

    杨吉庆; 黄兆样; 梁杰; 夏志远; 翟仙敦; 莫耀南

    2016-01-01

    Objective To review the researches on the telomere length in different tissues or cell and its correlation to forensic age estimation. Methods A systematic review was made by referring the latest literatures on the structure of telomere,the methods for measuring telomere length,its correlations to forensic age estimation as well as the influencing factors etc. Results Telomere length in different tissues or cells was significant correlation to forensic age estimation. Conclusion Determination of telomere length is very helpful in forensic age estimation.%目的:对不同组织细胞端粒长度与法医学年龄关系的研究进行综述,为相关研究提供参考。方法参考近年来有关文献,对端粒的结构及功能、端粒长度的测定方法、不同组织细胞端粒长度与法医学年龄的关系,以及端粒长度的影响因素等方面进行系统回顾。结果不同组织细胞端粒长度与法医学年龄关系显著。结论测定端粒长度对于法医学年龄推断具有重要意义。

  16. The Use of Neuropathic Pain Drugs in Children with Sickle Cell Disease is Associated with Older Age, Female Gender and Longer Length of Hospital Stay

    Science.gov (United States)

    Brandow, Amanda M.; Farley, Rebecca A.; Dasgupta, Mahua; Hoffmann, Raymond G.; Panepinto, Julie A.

    2014-01-01

    Although neuropathic pain is increasingly recognized in sickle cell disease (SCD), it is unknown how neuropathic pain drugs are used in children with SCD. Thus, we investigated use of these drugs and hypothesized older age and female gender are associated with increased neuropathic drug use and the use of these drugs is associated with longer length of stay. We analyzed the Pediatric Health Information System (2004-09) including all inpatient visits 0-18 years with any SCD-related (all genotypes) discharge diagnosis. To limit confounding we excluded psychiatric and seizure visits. Antiepileptics, tricyclic antidepressants, and selective serotonin reuptake inhibitors were drugs of interest. Generalized Estimating Equations determined the impact of age and gender on neuropathic drug use and the impact of neuropathic drug use on length of stay. We analyzed 53,557 visits; 2.9% received ≥1 neuropathic drugs. The odds of receiving a neuropathic drug increased significantly with age [Reference group 0-4 yrs: 5-10, OR 5.7; 11-14, OR 12.5; 15-18, OR 22.8; all pNeuropathic drug use was associated with longer length of stay [RR 8.3; pNeuropathic drug use in children with SCD was associated with older age, female gender, and longer length of stay. PMID:25222053

  17. Development and Psychometric Evaluation of a New Instrument for Measuring Sleep Length and Television and Computer Habits of Swedish School-Age Children

    Science.gov (United States)

    Garmy, Pernilla; Jakobsson, Ulf; Nyberg, Per

    2012-01-01

    The aim was to develop a new instrument for measuring length of sleep as well as television and computer habits in school-age children. A questionnaire was constructed for use when children visit the school health care unit. Three aspects of the validity of the questionnaire were examined: its face validity, content validity, and construct…

  18. Algorithm-Based Fetal Gender Determination Using X and Y Mini-Short Tandem Repeats at Early Gestational Ages

    Directory of Open Access Journals (Sweden)

    Aghanoori

    2016-02-01

    Full Text Available Background Detection of fetal DNA in maternal blood has been examined by many research groups for a few years; thereby, scientists have a shorter way to take to approach prenatal diagnosis of abnormal pregnancies. The Y chromosome sequences have recently become the most common applicable indices for fetal sex determination. Objectives We conducted an algorithmic X and Y mini-Short Tandem Repeats (STRs genotyping method that could solve the problem of false negative (no detection of Y sequences results of previous methods. Patients and Methods Blood samples were obtained from 106 pregnant women and their spouses. Conventional PCR amplified 19 mini-Short Tandem Repeats (STRs and three non-STR markers, which were subsequently genotyped by the means of Polyacrylamide gel electrophoresis (PAGE. Results Sensitivity and specificity of the mini-STR genotyping method for fetal DNA detection were calculated (95.9% and 98%, respectively with a confidence interval of 95%. In addition, sensitivity and informativeness were computed for each of the single mini-STR markers in our conventional PCR method. We also introduced the minimum number of mini-STRs needed to reach maximum validity for fetal gender determination in clinical settings. Conclusions Algorithm-based mini-STR genotyping method significantly increases the reliability (sensitivity and specificity of gender determination using free fetal DNA and could be applied in prenatal clinical testing.

  19. Neonatal Repeated Exposure to Isoflurane not Sevoflurane in Mice Reversibly Impaired Spatial Cognition at Juvenile-Age.

    Science.gov (United States)

    Liu, Jianhui; Zhao, Yanhong; Yang, Junjun; Zhang, Xiaoqing; Zhang, Wei; Wang, Peijun

    2017-02-01

    Inhalation anesthetics facilitate surgical procedures in millions of children each year. However, animal studies demonstrate that exposure to the inhalation anesthetic isoflurane may cause neuronal cell death in developing brains. The long-term cytotoxic effects of sevoflurane, the most popular pediatric anesthetic, have not been compared with isoflurane. Thus, this study was designed to compare the effects of equipotent doses of these two anesthetics on neonatal long-term neurotoxicity. Postnatal 7-day-old (P7) C57/BL male mice were exposed to 1.5% isoflurane or 2.2% sevoflurane 2 h a day for 3 days. Non-anesthetized mice served as controls. The effects of anesthesia on learning and memory were assessed using the Morris Water Maze (MWM) at Postnatal days 30 (P30) and P60 respectively. The hippocampal content of N-methyl-D-aspartate receptor subunits (NMDA), brain-derived neurotrophic factor (BDNF), and synaptophysin (Syn) were determined by Western Blot. Neuron structure and apoptosis were assessed via Nissl and TUNEL staining, respectively. The isoflurane group exhibited cognitive impairment at P30. Repeated inhalation of isoflurane or sevoflurane caused different degrees of apoptosis and damaged hippocampal neurons in neonatal mice, particularly isoflurane. In neonatal mice, repeated exposure to isoflurane, but not sevoflurane, caused spatial cognitive impairments in juvenile mice. Our findings suggest that isoflurane induces significantly greater neurodegeneration than an equipotent minimum alveolar concentration of sevoflurane.

  20. Cloning of full-length cDNA of Microsporum canis membrane protein PQ-loop repeat protein gene%犬小孢子菌膜蛋白PQ-LRP基因全长cDNA的克隆

    Institute of Scientific and Technical Information of China (English)

    庞娟; 祝逸平; 杨国玲

    2012-01-01

    Objective To clone the full-length cDNA of Microsporum canis membrane protein PQ-loop repeat protein (PQ-LRP) gene,so as to investigate the roles of PQ-LRP in the pathogenesis of tinea capitis.Methods A Microsporum canis strain (A518) from a patient with tinea capitis served as the experimental strain.Rapid cDNA end amplification (RACE) was performed to clone the full length cDNA sequence of PQLRP gene.Bioinformatics methods were used to make a preliminary functional analysis of the gene.Results The cDNA of PQ-LRP gene was obtained with a full length of 1522 bp,including the 5' untranslated region (49 bp),coding region (1080 bp) and 3' untranslated region (393 bp).The coding region encoded a protein precursor including 359 amino acid residues.The cloned cDNA of PQ-LRP gene shared an 81% nucleotide identity with that of Trichophyton tonsurans and a 79% nucleotide identity with that of Trichophyton rubrum.Conclusions The full-length cDNA of Microsporum canis membrane protein PQ-LRP gene has been successfully cloned,which will provide an important basis for further researches into the roles of PQ-LRP in Microsporum canis-associated diseases.%目的 克隆犬小孢子菌膜蛋白PQ-LRP(PQ-loop repeat protein)基因全长cDNA,探讨在头癣发病机制中的作用.方法 选用犬小孢子菌头癣株(A518)为实验株,采用cDNA快速末端扩增法(RACE),克隆PQ-LRP基因的全长序列.结合生物信息学方法对获得的序列进行初步功能分析.结果 获得犬小孢子菌PQ-LRP全长序列为1522 bp,拥有一个1080 bp的开放阅读框,编码359个氨基酸,5 '非编码区为49 bp,3 '非编码区为393 bp;同源性比对与断发毛癣菌的PQ-LRP同源性达到81%,与红色毛癣菌PQ-LRP同源性达到79%.结论 克隆出犬小孢子菌膜蛋白PQ-LRP cDNA全长序列,为研究膜蛋白PQ-LRP基因在犬小孢子菌病中的功能奠定基础.

  1. Reduced telomere length is not associated with early signs of vascular aging in young men born after intrauterine growth restriction: a paradox?

    DEFF Research Database (Denmark)

    Laganovic, M.; Bendix, L.; Rubelj, I.;

    2014-01-01

    Objective: The mechanisms that increase cardiovascular risk in individuals born small for gestational age (SGA) are not well understood. Telomere shortening has been suggested to be a predictor of disease onset. Our aim was to determine whether impaired intrauterine growth is associated with early...... signs of vascular aging and whether telomere length could be a biomarker of this pathway. Methods: One hundred and fourteen healthy young men born SGA or after normal pregnancy [appropriate for gestational age (AGA)] were enrolled. Patient data were gathered from questionnaires and clinical exams...

  2. Age, growth and length-weight relationship of the white skate, Rostroraja alba (Linnaeus, 1758 (Chondrichthyans: Rajidae, from the Gulf of Gabes (Tunisia, Central Mediterranean

    Directory of Open Access Journals (Sweden)

    Hasna Kadri

    2014-06-01

    Full Text Available Objective: To investigate the length distribution, sex ratio, length-weight relationship, age and growth of Rostroraja alba in the Gulf of Gabes. Methods: This study estimated age and growth of the white skate, Rostroraja alba by counting vertebral band pairs from 112 specimens taken by commercial fisheries during 2006-2009 from the Gulf of Gabes (Southern Tunisia, Central Mediterranean Sea. Results: This is the first and only known information in regards to the age and growth of this species in Tunisia. Vertebra diameter was strongly correlated with total length and age, which were expressed by linear or cubic regression equations. The oldest female in this study was 35 years and 160 cm, whereas the oldest male was 32 years and 150 cm. The von Bertalanffy growth parameters were TL∞=(202.26±3.40 cm, K=(0.040±0.038/year and t0=(1.84±0.01 10 -1 /year for females and TL∞=(198.60±3.61 cm, K=(0.060±0.076/year and t0=(1.28±0.04/year for males. Conclusions: This study would be an effective tool for fishery biologists, managers and conservationists to initiate management strategies and regulations for the sustainable conservation of the remaining stocks of this species in the Gulf of Gabes (Southern Tunisia ecosystem

  3. Age, growth and length-weight relationship of the white skate, Rostroraja alba (Linnaeus, 1758) (Chondrichthyans:Rajidae), from the Gulf of Gabes (Tunisia, Central Mediterranean)

    Institute of Scientific and Technical Information of China (English)

    Hasna Kadri; Sondes Marouani; Mohamed Nejmeddine Bradai; Abderrahmen Bouan; Eric Morize

    2014-01-01

    Objective:To investigate the length distribution, sex ratio, length-weight relationship, age and growth of Rostroraja alba in the Gulf of Gabes. Methods:This study estimated age and growth of the white skate, Rostroraja alba by counting vertebral band pairs from 112 specimens taken by commercial fisheries during 2006-2009 from the Gulf of Gabes (Southern Tunisia, Central Mediterranean Sea). Results: This is the first and only known information in regards to the age and growth of this species in Tunisia. Vertebra diameter was strongly correlated with total length and age, which were expressed by linear or cubic regression equations. The oldest female in this study was 35 years and 160 cm, whereas the oldest male was 32 years and 150 cm. The von Bertalanffy growth parameters were TL∞=(202.26±3.40) cm, K=(0.040±0.038)/year and t0=(1.84±0.01) 10-1/year for females and TL∞=(198.60±3.61) cm, K=(0.060±0.076)/year and t0=(1.28±0.04)/year for males. Conclusions: This study would be an effective tool for fishery biologists, managers and conservationists to initiate management strategies and regulations for the sustainable conservation of the remaining stocks of this species in the Gulf of Gabes (Southern Tunisia) ecosystem.

  4. Clonal Propagation of Khaya senegalensis: The Effects of Stem Length, Leaf Area, Auxins, Smoke Solution, and Stockplant Age

    Directory of Open Access Journals (Sweden)

    Catherine Ky-Dembele

    2011-01-01

    Full Text Available Khaya senegalensis is a multipurpose African timber species. The development of clonal propagation could improve plantation establishment, which is currently impeded by mahogany shoot borer. To examine its potential for clonal propagation, the effects of cutting length, leaf area, stockplant maturation, auxin, and smoke solution treatments were investigated. Leafy cuttings rooted well (up to 80% compared to leafless cuttings (0%. Cuttings taken from seedlings rooted well (at least 95%, but cuttings obtained from older trees rooted poorly (5% maximum. The rooting ability of cuttings collected from older trees was improved (16% maximum by pollarding. Auxin application enhanced root length and the number of roots while smoke solution did not improve cuttings' rooting ability. These results indicate that juvenile K. senegalensis is amenable to clonal propagation, but further work is required to improve the rooting of cuttings from mature trees.

  5. Repeated intra-specific divergence in lifespan and ageing of African annual fishes along an aridity gradient

    DEFF Research Database (Denmark)

    Blažek, Radim; Polačik, Matej; Kačer, Petr

    2016-01-01

    to extended lifespan and slower ageing as a consequence of condition-dependent survival. Using within-species contrasts of eight natural populations of Nothobranchius fishes in common garden experiments, we demonstrate that populations originating from dry regions (with short life expectancy) had shorter...

  6. Comparison of a PCR-restriction fragment length polymorphism (PCR-RFLP) assay to pulsed-field gel electrophoresis to determine the effect of repeated subculture and prolonged storage on RFLP patterns of Shiga toxin-producing Escherichia coli O157:H7.

    Science.gov (United States)

    Shima, Kensuke; Wu, Yuluo; Sugimoto, Norihiko; Asakura, Masahiro; Nishimura, Kazuhiko; Yamasaki, Shinji

    2006-11-01

    In this study, we compared a recently developed PCR-restriction fragment length polymorphism (PCR-RFLP) assay with pulsed-field gel electrophoresis (PFGE) using three different Shiga toxin-producing Escherichia coli (STEC) strains to understand whether repeated subculture in vitro and prolonged storage at room temperature affect the RFLP patterns of STEC. The PFGE profiles of the STEC strains changed by 1 to 8 fragments after repeated subculture and prolonged storage; one strain was no longer clonal after repeated subculture compared to the original isolate according to the Tenover criteria. In contrast, RFLP patterns obtained by PCR-RFLP were identical after repeated subculture and prolonged storage. These data clearly indicate that the PCR-RFLP assay which is based on the diversity of region V, a regulatory region of Stx-phage, was not affected by repeated subculture and prolonged storage and is a more practical and reliable method for molecular typing of STEC strains.

  7. Coronary bypass surgery in patients aged 70 years and over: Mortality, morbidity, & length of stay. Dar al-fouad experience

    Directory of Open Access Journals (Sweden)

    Ahmed Ghali

    2014-03-01

    This study supports the continued performance of coronary artery bypass grafting in patients 70 years. Advanced age alone should not deter a cardiac surgeon from offering such a potentially beneficial intervention.

  8. The feasibility of bomb radiocarbon analysis to support an age-at-length relationship for red abalone, Haliotis rufescens Swainson in northern California

    Energy Technology Data Exchange (ETDEWEB)

    Leaf, R T; Andrews, A H; Cailliet, G M; Brown, T A

    2009-01-07

    Analysis of bomb generated radiocarbon ({sup 14}C) changes in a red abalone, Haliotis rufescens Swainson shell was used to investigate age-at-length relationships derived from data from a previous multi-year, multi-site tag-recapture study. Shell carbonate was extracted from four successive growth trajectory locations in a single shell with a length of 251 mm MSL. Extraction locations were based on VBGF predictions and chosen to span the initial rise of the {sup 14}C-bomb pulse that is known to have occurred in surface ocean waters during 1958 {+-} 1 y in the northeast Pacific. The close temporal correspondence of the red abalone sample series to regional {Delta}{sup 14}C records demonstrated the utility of the technique for validating age-at-length relationships for the red abalone. The findings provided support for a mean VBGF derived age of 32 y (range 30 to 33 y) for the specimen; however, the analysis of {sup 14}C data indicated that the specimen could be older.

  9. The Effects of Repeated Reading on the Fluency and Comprehension Skills of Elementary-Age Students with Learning Disabilities (LD), 2001-2011: A Review of Research and Practice

    Science.gov (United States)

    Strickland, Whitney D.; Boon, Richard T.; Spencer, Vicky G.

    2013-01-01

    This article provides an extensive review of the literature on the use of repeated reading to improve the reading fluency and comprehension skills of elementary-age students with learning disabilities. A systematic review of the published literature from 2001 to 2011 was conducted and nineteen (N = 19) research-based repeated reading studies were…

  10. Deletion of the major peroxiredoxin Tsa1 alters telomere length homeostasis

    OpenAIRE

    2013-01-01

    Reactive oxygen species (ROS) are proposed to play a major role in telomere length alterations during aging. The mechanisms by which ROS disrupt telomeres remain unclear. In Saccharomyces cerevisiae, telomere DNA consists of TG(1-3) repeats, which are maintained primarily by telomerase. Telomere length maintenance can be modulated by the expression level of telomerase subunits and telomerase activity. Additionally, telomerase-mediated telomere repeat addition is negatively modulated by the le...

  11. Automated Assay of Telomere Length Measurement and Informatics for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort

    Science.gov (United States)

    Lapham, Kyle; Kvale, Mark N.; Lin, Jue; Connell, Sheryl; Croen, Lisa A.; Dispensa, Brad P.; Fang, Lynn; Hesselson, Stephanie; Hoffmann, Thomas J.; Iribarren, Carlos; Jorgenson, Eric; Kushi, Lawrence H.; Ludwig, Dana; Matsuguchi, Tetsuya; McGuire, William B.; Miles, Sunita; Quesenberry, Charles P.; Rowell, Sarah; Sadler, Marianne; Sakoda, Lori C.; Smethurst, David; Somkin, Carol P.; Van Den Eeden, Stephen K.; Walter, Lawrence; Whitmer, Rachel A.; Kwok, Pui-Yan; Risch, Neil; Schaefer, Catherine; Blackburn, Elizabeth H.

    2015-01-01

    The Kaiser Permanente Research Program on Genes, Environment, and Health (RPGEH) Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort includes DNA specimens extracted from saliva samples of 110,266 individuals. Because of its relationship to aging, telomere length measurement was considered an important biomarker to develop on these subjects. To assay relative telomere length (TL) on this large cohort over a short time period, we created a novel high throughput robotic system for TL analysis and informatics. Samples were run in triplicate, along with control samples, in a randomized design. As part of quality control, we determined the within-sample variability and employed thresholds for the elimination of outlying measurements. Of 106,902 samples assayed, 105,539 (98.7%) passed all quality control (QC) measures. As expected, TL in general showed a decline with age and a sex difference. While telomeres showed a negative correlation with age up to 75 years, in those older than 75 years, age positively correlated with longer telomeres, indicative of an association of longer telomeres with more years of survival in those older than 75. Furthermore, while females in general had longer telomeres than males, this difference was significant only for those older than age 50. An additional novel finding was that the variance of TL between individuals increased with age. This study establishes reliable assay and analysis methodologies for measurement of TL in large, population-based human studies. The GERA cohort represents the largest currently available such resource, linked to comprehensive electronic health and genotype data for analysis. PMID:26092717

  12. The concept of the Equivalent Length of Life for quantifying differences in age-at-death distributions across countries

    NARCIS (Netherlands)

    Muszyńska, M.; Janssen, F.

    2016-01-01

    Life expectancy, that is the mean age at death in a life table, is the most common measure used to describe and compare mortality distributions. Alternatives to life expectancy that have been proposed so far have also referred to only a single parameter of the mortality distribution. We propose to s

  13. Analysis of participation and performance in athletes by age group in ultramarathons of more than 200 km in length

    Directory of Open Access Journals (Sweden)

    Zingg MA

    2013-04-01

    Full Text Available Matthias Zingg,1 Beat Knechtle,1,2 Christoph A Rüst,1 Thomas Rosemann,1 Romuald Lepers3 1Institute of General Practice and Health Services Research, University of Zurich, Zurich, Switzerland; 2Gesundheitszentrum St Gallen, St Gallen, Switzerland; 3INSERM U1093, Faculty of Sport Sciences, University of Burgundy, Dijon, France Background: Participation and performance trends for athletes by age group have been investigated for marathoners and ultramarathoners competing in races up to 161 km, but not for longer distances of more than 200 km. Methods: Participation and performance trends in athletes by age group in the Badwater (217 km and Spartathlon (246 km races were compared from 2000 to 2012. Results: The number of female and male finishers increased in both races across years (P 0.05. In Spartathlon, the age of the annual five fastest finishers was unchanged at 39.7 ± 2.4 years for men and 44.6 ± 3.2 years for women (P > 0.05. In Badwater, running speed increased in men from 7.9 ± 0.7 km/hour to 8.7 ± 0.6 km/hour (r2 = 0.51, P 0.05. In Badwater, the number of men in age groups 30–34 years (r2 = 0.37, P = 0.03 and 40–44 years (r2 = 0.75, P < 0.01 increased. In Spartathlon, the number of men increased in the age group 40–44 years (r2 = 0.33, P = 0.04. Men in age groups 30–34 (r2 = 0.64, P < 0.01, 35–39 (r2 = 0.33, P = 0.04, 40–44 (r2 = 0.34, P = 0.04, and 55–59 years (r2 = 0.40, P = 0.02 improved running speed in Badwater. In Spartathlon, no change in running speed was observed. Conclusion: The fastest finishers in ultramarathons more than 200 km in distance were 40–45 years old and have to be classified as “master runners” by definition. In contrast to reports of marathoners and ultramarathoners competing in races of 161 km in distance, the increase in participation and the improvement in performance by age group were less pronounced in ultramarathoners competing in races of more than 200 km. Keywords: ultra

  14. Semen analysis in fertile patients undergoing vasectomy: reference values and variations according to age, length of sexual abstinence, seasonality, smoking habits and caffeine intake

    Directory of Open Access Journals (Sweden)

    Bernardo Passos Sobreiro

    Full Text Available CONTEXT AND OBJECTIVE: Recent studies have shown regional and population differences in semen characteristics. The objective was to establish reference values for semen analysis and to verify the effect that age, length of sexual abstinence, seasonality, smoking habits and coffee consumption have on fertile individuals’ semen characteristics. DESIGN AND SETTING: Prospective study in the Urology Division, Hospital das Clínicas, Universidade de São Paulo. METHODS: Between September 1999 and August 2002, 500 fertile men requesting a vasectomy for sterilization purposes were asked to provide a semen sample before the vasectomy. We evaluated the effects of age, sexual abstinence, seasonality, smoking and coffee consumption on semen characteristics. RESULTS: Compared with World Health Organization values, 87.2% of the patients presented sperm morphology below the normal level. A significant decline in semen volume, sperm motility and sperm morphology in patients over 45 years of age was observed. In patients with 5 days or more of abstinence, there was reduced sperm motility. The lowest values for sperm concentration, motility and morphology were observed in summer and the highest in winter. No differences in semen parameters relating to smoking were detected. Patients who drank six or more cups of coffee per day presented higher sperm motility. CONCLUSIONS: Our sample had a very low percentage of normal sperm morphology. Only sperm morphology showed a high abnormality rate. Differences in semen parameters with regard to age, length of sexual abstinence, seasonality and coffee consumption were identified. No differences relating to smoking were detected.

  15. The Change of Stretched Penile Length and Anthropometric Data in Korean Children Aged 0-14 Years: Comparative Study of Last 25 Years.

    Science.gov (United States)

    Park, Sungchan; Chung, Jae Min; Kang, Dong Il; Ryu, Dong Soo; Cho, Won Yeol; Lee, Sang Don

    2016-10-01

    There has been a great improvement in height and weight of Korean children owing to economic development over the last 25 years. This study aimed to evaluate the penile length of Korean children today and to compare it with a previous Korean study reported in 1987. The cross-sectional study was conducted with 909 Korean boys aged 0-14 years who had been brought to outpatient clinics of five tertiary hospitals (Busan, Ulsan, and Changwon) between September 2013 and May 2015. The stretched penile length (SPL) was measured and the testicular size was measured using orchidometry (mL). Student's t-test or Mann-Whitney U test was used to compare the result of our study and the study reported in 1987. SPL of Korean children gradually increased from 4.1 ± 0.8 cm at 0-1 year old to 9.6 ± 3.0 cm at 13-14 years old, the most rapidly during the age of 13. While body weight and testicular size significantly increased from 1987 in most of age groups, there were no significant changes in SPL although there was in some age groups. Height decreased in the infants 6 years old. With the great economic development over the last quarter century in Korea, height, body weight, and testicular size of children significantly increased but there was no significant change in SPL except penile growth pattern.

  16. Correlation of choroidal thickness and volume measurements with axial length and age using swept source optical coherence tomography and optical low-coherence reflectometry.

    Science.gov (United States)

    Michalewski, Janusz; Michalewska, Zofia; Nawrocka, Zofia; Bednarski, Maciej; Nawrocki, Jerzy

    2014-01-01

    To report choroidal thickness and volume in healthy eyes using swept source optical coherence tomography (SS-OCT). A prospective observational study of 122 patients examined with swept source OCT (DRI-OCT, Topcon, Japan). In each eye, we performed 256 horizontal scans, 12 mm in length and centered on the fovea. We calculated choroidal thickness manually with a built-in caliper and automatically using DRI-OCT mapping software. Choroidal volume was also automatically calculated. We measured axial length with optical low-coherence reflectometry (Lenstar LS 900, Haag-Streit, Switzerland). The choroid has focally increased thickness under the fovea. Choroid was thinnest in the outer nasal quadrant. In stepwise regression analysis, age was estimated as the most significant factor correlating with decreased choroidal thickness (F=23.146, Pchoroidal thickness and volume maps. Choroidal thickness is increased at the fovea and is thinnest nasally. Age and axial length are critical for the estimation of choroidal thickness and volume. Choroidal measurements derived from SS-OCT images have potential value for objectively documenting disease-related choroidal thickness abnormalities and monitoring progressive changes over time.

  17. Telomerase activity and telomere length in Daphnia.

    Science.gov (United States)

    Schumpert, Charles; Nelson, Jacob; Kim, Eunsuk; Dudycha, Jeffry L; Patel, Rekha C

    2015-01-01

    Telomeres, comprised of short repetitive sequences, are essential for genome stability and have been studied in relation to cellular senescence and aging. Telomerase, the enzyme that adds telomeric repeats to chromosome ends, is essential for maintaining the overall telomere length. A lack of telomerase activity in mammalian somatic cells results in progressive shortening of telomeres with each cellular replication event. Mammals exhibit high rates of cell proliferation during embryonic and juvenile stages but very little somatic cell proliferation occurs during adult and senescent stages. The telomere hypothesis of cellular aging states that telomeres serve as an internal mitotic clock and telomere length erosion leads to cellular senescence and eventual cell death. In this report, we have examined telomerase activity, processivity, and telomere length in Daphnia, an organism that grows continuously throughout its life. Similar to insects, Daphnia telomeric repeat sequence was determined to be TTAGG and telomerase products with five-nucleotide periodicity were generated in the telomerase activity assay. We investigated telomerase function and telomere lengths in two closely related ecotypes of Daphnia with divergent lifespans, short-lived D. pulex and long-lived D. pulicaria. Our results indicate that there is no age-dependent decline in telomere length, telomerase activity, or processivity in short-lived D. pulex. On the contrary, a significant age dependent decline in telomere length, telomerase activity and processivity is observed during life span in long-lived D. pulicaria. While providing the first report on characterization of Daphnia telomeres and telomerase activity, our results also indicate that mechanisms other than telomere shortening may be responsible for the strikingly short life span of D. pulex.

  18. Telomerase Activity and Telomere Length in Daphnia

    Science.gov (United States)

    Schumpert, Charles; Nelson, Jacob; Kim, Eunsuk; Dudycha, Jeffry L.; Patel, Rekha C.

    2015-01-01

    Telomeres, comprised of short repetitive sequences, are essential for genome stability and have been studied in relation to cellular senescence and aging. Telomerase, the enzyme that adds telomeric repeats to chromosome ends, is essential for maintaining the overall telomere length. A lack of telomerase activity in mammalian somatic cells results in progressive shortening of telomeres with each cellular replication event. Mammals exhibit high rates of cell proliferation during embryonic and juvenile stages but very little somatic cell proliferation occurs during adult and senescent stages. The telomere hypothesis of cellular aging states that telomeres serve as an internal mitotic clock and telomere length erosion leads to cellular senescence and eventual cell death. In this report, we have examined telomerase activity, processivity, and telomere length in Daphnia, an organism that grows continuously throughout its life. Similar to insects, Daphnia telomeric repeat sequence was determined to be TTAGG and telomerase products with five-nucleotide periodicity were generated in the telomerase activity assay. We investigated telomerase function and telomere lengths in two closely related ecotypes of Daphnia with divergent lifespans, short-lived D. pulex and long-lived D. pulicaria. Our results indicate that there is no age-dependent decline in telomere length, telomerase activity, or processivity in short-lived D. pulex. On the contrary, a significant age dependent decline in telomere length, telomerase activity and processivity is observed during life span in long-lived D. pulicaria. While providing the first report on characterization of Daphnia telomeres and telomerase activity, our results also indicate that mechanisms other than telomere shortening may be responsible for the strikingly short life span of D. pulex. PMID:25962144

  19. Spectral-domain Optical Coherence Tomography Retinal and Choroidal Thickness Metric Repeatability in Age-related Macular Degeneration

    DEFF Research Database (Denmark)

    Hanumunthadu, Daren; Ilginis, Tomas; Restori, Marie

    2016-01-01

    ) macular subfields. Center point thickness and total macular volume were also included in the analysis. Manual subfoveal choroidal thickness measurements were made by a masked observer. RESULTS: A total of 40 eyes of 40 patients were included in this analysis (mean [± standard deviation] age: 74.1 [± 7...... for the center point was 47.5 μm (95% CI 46.2-48.7 μm). Images were also reviewed for the presence of segmentation error in the central macular subfield, and after exclusion of these eyes the revised CR for this subfield was 13.7 μm (95% CI 13.3-14.1 μm). The intrasession CR of subfoveal choroidal thickness...... was 34.7 μm (95% CI 33.7-35.7 μm). CONCLUSIONS: This study suggests that a change of greater than 31 μm in Spectralis SDOCT-derived retinal thickness measurement of the central macular subfield and 35 μm in subfoveal choroidal thickness is necessary to detect true clinical change associated with disease...

  20. Using postnatal age to determine test dates leads to misinterpretations when treatments alter gestation length: results from a collaborative behavioral teratology study in Japan.

    Science.gov (United States)

    Tachibana, T; Narita, H; Ogawa, T; Tanimura, T

    1998-01-01

    A collaborative study was conducted by researchers from 18 laboratories that participated in the Behavioral Teratology Meeting in Japan. Pregnant Sprague-Dawley rats from four breeders received subcutaneous injections of nicotine (6 mg/kg body weight) from day 7 to day 20 of gestation. Results of preweaning tests were closely related to length of gestation, and prolonged gestation was seen in the nicotine group. The effects of nicotine were compared with and without the adjustment of the mean difference in gestational lengths. Without the adjustment (i.e., by employing assessment in terms of postnatal day) several perplexing results were obtained, indicating that the nicotine group developed more quickly than the control group on several preweaning tests. By employing the adjustment, these perplexing results disappeared, indicating that the nicotine group developed more slowly than the control group. The merit of employing gestational day (or postcoital age) as an alternative index is emphasized.

  1. Evaluating the effectiveness of Washington state repeated job search services on the employment rate of prime-age female welfare recipients.

    Science.gov (United States)

    Hsiao, Cheng; Shen, Yan; Wang, Boqing; Weeks, Greg

    2008-07-01

    This paper uses an unbalanced panel dataset to evaluate how repeated job search services (JSS) and personal characteristics affect the employment rate of the prime-age female welfare recipients in the State of Washington. We propose a transition probability model to take into account issues of sample attrition, sample refreshment and duration dependence. We also generalize Honoré and Kyriazidou's [Honoré, B.E., Kyriazidou, E., 2000. Panel data discrete choice models with lagged dependent variables. Econometrica 68 (4), 839-874] conditional maximum likelihood estimator to allow for the presence of individual-specific effects. A limited information test is suggested to test for selection issues in non-experimental data. The specification tests indicate that the (conditional on the set of the confounding variables considered) assumptions of no selection due to unobservables and/or no unobserved individual-specific effects are not violated. Our findings indicate that the first job search service does have positive and significant impacts on the employment rate. However, providing repeated JSS to the same client has no significant impact. Further, we find that there are significant experience-enhancing effects. These findings suggest that providing one job search services training to individuals may have a lasting impact on raising their employment rates.

  2. Mappability and Read Length

    Directory of Open Access Journals (Sweden)

    Wentian eLi

    2014-11-01

    Full Text Available Power-law distributions are the main functional form forthe distribution of repeat size and repeat copy number in the human genome. When the genome is broken into fragments for sequencing, the limited size offragments and reads may prevent an unique alignment of repeatsequences to the reference sequence. Repeats in the human genome canbe as long as $10^4$ bases, or $10^5-10^6$ bases when allowing for mismatches between repeat units. Sequence reads from these regions are therefore unmappable when the read length is in the range of $10^3$ bases.With the read length of exactly 1000 bases, slightly more than 1% of theassembled genome, and slightly less than 1% of the 1kbreads, are unmappable, excluding the unassembled portion of the humangenome (8% in GRCh37. The slow decay (long tail ofthe power-law function implies a diminishing return in convertingunmappable regions/reads to become mappable with the increase of theread length, with the understanding that increasing read length willalways move towards the direction of 100% mappability.

  3. Age, growth and length-weight relationship of the rough skate, Raja radula (Linnaeus, 1758) (Chondrichthyans:Rajidae), from the Gulf of Gabes (Tunisia, Central Mediterranean)

    Institute of Scientific and Technical Information of China (English)

    Hasna Kadri; Sondes Marouani; Mohamed Nejmeddine Bradai; Abderrahmen Bouan; Eric Morize

    2014-01-01

    Objective:To investigate the length distribution, sex ratio, length-weight relationship, age and growth of Raja radula in the Gulf of Gabes. Methods: The age and growth characteristic of the rough skate (Raja radula) inhabiting in the Gulf of Gabes (Central Mediterranean Sea) was determined. A total of 1 250 specimens were sampled. According to the marginal increment band its growth was annual. Results: The growth parameters were derived by using the von-Bertalanffy method and were separately evaluated as follows:TL∞=97.2 cm, K= 0.15 y-1, to= 0.35, and W∞= 5.28 kg, and TL∞=76.4 cm, K=0.22 y-1, to=0.16, and W∞=3.77 kg, for females and males respetively. The maximum age was 12 years for females and 10 years for males. Conclusions:Results from this research will provide a starting point to develop a management plan for the rough skate in the Gulf of Gabes. Further investigations are necessary to quantify the impact of the existing regulations on the population dynamics and recruitment patterns of this species in the region.

  4. Rosa26-GFP direct repeat (RaDR-GFP mice reveal tissue- and age-dependence of homologous recombination in mammals in vivo.

    Directory of Open Access Journals (Sweden)

    Michelle R Sukup-Jackson

    2014-06-01

    Full Text Available Homologous recombination (HR is critical for the repair of double strand breaks and broken replication forks. Although HR is mostly error free, inherent or environmental conditions that either suppress or induce HR cause genomic instability. Despite its importance in carcinogenesis, due to limitations in our ability to detect HR in vivo, little is known about HR in mammalian tissues. Here, we describe a mouse model in which a direct repeat HR substrate is targeted to the ubiquitously expressed Rosa26 locus. In the Rosa26 Direct Repeat-GFP (RaDR-GFP mice, HR between two truncated EGFP expression cassettes can yield a fluorescent signal. In-house image analysis software provides a rapid method for quantifying recombination events within intact tissues, and the frequency of recombinant cells can be evaluated by flow cytometry. A comparison among 11 tissues shows that the frequency of recombinant cells varies by more than two orders of magnitude among tissues, wherein HR in the brain is the lowest. Additionally, de novo recombination events accumulate with age in the colon, showing that this mouse model can be used to study the impact of chronic exposures on genomic stability. Exposure to N-methyl-N-nitrosourea, an alkylating agent similar to the cancer chemotherapeutic temozolomide, shows that the colon, liver and pancreas are susceptible to DNA damage-induced HR. Finally, histological analysis of the underlying cell types reveals that pancreatic acinar cells and liver hepatocytes undergo HR and also that HR can be specifically detected in colonic somatic stem cells. Taken together, the RaDR-GFP mouse model provides new understanding of how tissue and age impact susceptibility to HR, and enables future studies of genetic, environmental and physiological factors that modulate HR in mammals.

  5. Chronic caffeine consumption prevents cognitive decline from young to middle age in rats, and is associated with increased length, branching, and spine density of basal dendrites in CA1 hippocampal neurons.

    Science.gov (United States)

    Vila-Luna, S; Cabrera-Isidoro, S; Vila-Luna, L; Juárez-Díaz, I; Bata-García, J L; Alvarez-Cervera, F J; Zapata-Vázquez, R E; Arankowsky-Sandoval, G; Heredia-López, F; Flores, G; Góngora-Alfaro, J L

    2012-01-27

    Chronic caffeine consumption has been inversely associated with the risk of developing dementia and Alzheimer's disease. Here we assessed whether chronic caffeine treatment prevents the behavioral and cognitive decline that male Wistar rats experience from young (≈3 months) to middle age (≈10 months). When animals were young they were evaluated at weekly intervals in three tests: motor activity habituation in the open field (30-min sessions at the same time on consecutive days), continuous spontaneous alternation in the Y-maze (8 min), and elevated plus-maze (5 min). Afterward, rats from the same litter were randomly assigned either to a caffeine-treated group (n=13) or a control group (n=11), which received only tap water. Caffeine treatment (5 mg/kg/day) began when animals were ≈4 months old, and lasted for 6 months. Behavioral tests were repeated from day 14 to day 28 after caffeine withdrawal, a time period that is far in excess for the full excretion of a caffeine dose in this species. Thirty days after caffeine discontinuation brains were processed for Golgi-Cox staining. Compared with controls, we found that middle-aged rats that had chronically consumed low doses of caffeine (1) maintained their locomotor habituation during the second consecutive day exposure to the open field (an index of non-associative learning), (2) maintained their exploratory drive to complete the conventional minimum of nine arm visits required to calculate the alternation performance in the Y-maze in a greater proportion, (3) maintained their alternation percentage above chance level (an index of working memory), and (4) did not increase the anxiety indexes assessed by measuring the time spent in the open arms of the elevated plus maze. In addition, morphometric analysis of hippocampal neurons revealed that dendritic branching (90-140 μm from the soma), length of 4th and 5th order branches, total dendritic length, and spine density in distal dendritic branches were greater in

  6. The effect of technical replicate (repeats) on Nix Pro Color Sensor™ measurement precision for meat: A case-study on aged beef colour stability.

    Science.gov (United States)

    Holman, Benjamin W B; Collins, Damian; Kilgannon, Ashleigh K; Hopkins, David L

    2017-09-04

    The Nix Pro Colour Sensor™ (NIX) can be potentially used to measure meat colour, but procedural guidelines that assure measurement reproducibility and repeatability (precision) must first be established. Technical replicate number (r) will minimise response variation, measureable as standard error of predicted mean (SEM), and contribute to improved precision. Consequently, we aimed to explore the effects of r on NIX precision when measuring aged beef colour (colorimetrics; L*, a*, b*, hue and chroma values). Each colorimetric SEM declined with increasing r to indicate improved precision and followed a diminishing rate of improvement that allowed us to recommend r=7 for meat colour studies using the NIX. This definition was based on practical limitations and a* variability, as additional r would be required if other colorimetrics or advanced levels of precision are necessary. Beef ageing and display period, holding temperature, loin and sampled portion were also found to contribute to colorimetric variation, but were incorporated within our definition of r. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  7. English Language Learners' Nonword Repetition Performance: The Influence of Age, L2 Vocabulary Size, Length of L2 Exposure, and L1 Phonology.

    Science.gov (United States)

    Duncan, Tamara Sorenson; Paradis, Johanne

    2016-02-01

    This study examined individual differences in English language learners' (ELLs) nonword repetition (NWR) accuracy, focusing on the effects of age, English vocabulary size, length of exposure to English, and first-language (L1) phonology. Participants were 75 typically developing ELLs (mean age 5;8 [years;months]) whose exposure to English began on average at age 4;4. Children spoke either a Chinese language or South Asian language as an L1 and were given English standardized tests for NWR and receptive vocabulary. Although the majority of ELLs scored within or above the monolingual normal range (71%), 29% scored below. Mixed logistic regression modeling revealed that a larger English vocabulary, longer English exposure, South Asian L1, and older age all had significant and positive effects on ELLs' NWR accuracy. Error analyses revealed the following L1 effect: onset consonants were produced more accurately than codas overall, but this effect was stronger for the Chinese group whose L1s have a more limited coda inventory compared with English. ELLs' NWR performance is influenced by a number of factors. Consideration of these factors is important in deciding whether monolingual norm referencing is appropriate for ELL children.

  8. An exploratory examination of the relationships among emotional intelligence, elementary school science teacher self-efficacy, length of teaching experience, race/ethnicity, gender, and age

    Science.gov (United States)

    Okech, Allan P.

    The purpose of the study was to examine the relationships among emotional intelligence, teacher self-efficacy, length of teaching experience, and age in a sample of south Texas public school teachers. Additionally, the study examined differences in emotional intelligence between male teachers and female teachers, and among African American, Hispanics, and White teachers. Participants were 180 elementary science teachers from south Texas public schools. The sample was made up of 14 (7.8%) males and 166 (92.2%) females. Regarding race/ethnicity, the study sample consisted of 31 (17.2%) African Americans (3 males and 28 females), 49 (27.2) Hispanics (7 males and 42 females), 98 (54.4%) Whites (3 males and 95 females), and 2 (1.1%) "Other" (1 male and 1 female). Participants ranged in age from 23 years to 65 years. Five hypotheses were proposed and tested to address the relationships under investigation. The study employed a mixed methods---correlational and causal-comparative---research design approach. Three instruments, the Multifactor Emotional Intelligence Scale (Mayer, Caruso, & Salovey, 1999), the Science Teaching Efficacy Beliefs Instrument (Riggs & Enochs, 1990), and a demographics questionnaire were utilized to collect the data. An independent-measures t test, the Pearson r, and the one-way MANOVA were used to analyze the data. A Significant positive relationship was found between "emotional intelligence" and "teacher self-efficacy." Data analyses, however, failed to support hypothesized relationships between "emotional intelligence" and "length of teaching experience," and between "emotional intelligence" and "age". Additionally, statistical analyses of the data collected for this study supported predicted statistically significant differences in "emotional intelligence" between male and female teachers, and among the three race/ethnicity groupings. Based on these findings, recommendations for the application of the construct of "emotional intelligence" in

  9. Telomere length is a biomarker of cumulative oxidative stress, biologic age, and an independent predictor of survival and therapeutic treatment requirement associated with smoking behavior.

    Science.gov (United States)

    Babizhayev, Mark A; Savel'yeva, Ekaterina L; Moskvina, Svetlana N; Yegorov, Yegor E

    2011-11-01

    Globally, tobacco use is associated with 5 million deaths per annum and is regarded as one of the leading causes of premature death. Major chronic disorders associated with smoking include cardiovascular diseases, several types of cancer, and chronic obstructive pulmonary disease (lung problems). Cigarette smoking (CS) generates a cumulative oxidative stress, which may contribute to the pathogenesis of chronic diseases. Mainstream and side stream gas-phase smoke each have about the same concentration of reactive free radical species, about 1 × 10(16) radicals per cigarette (or 5 × 10(14) per puff). This effect is critical in understanding the biologic effects of smoke. Several lines of evidence suggest that cigarette smoke constituents can directly activate vascular reactive oxygen species production. In this work we present multiple evidence that CS provide the important risk factors in many age-related diseases, and is associated with increased cumulative and systemic oxidative stress and inflammation. The cited processes are marked by increased white blood cell (leucocytes, WBCs) turnover. The data suggest an alteration of the circulating WBCs by CS, resulting in increased adherence to endothelial cells. Telomeres are complex DNA-protein structures located at the end of eukaryotic chromosomes. Telomere length shortens with biologic age in all replicating somatic cells. It has been shown that tobacco smoking enhances telomere shortening in circulating human WBCs. Telomere attrition (expressed in WBCs) can serve as a biomarker of the cumulative oxidative stress and inflammation induced by smoking and, consequently, show the pace of biologic aging. We originally propose that patented specific oral formulations of nonhydrolized carnosine and carcinine provide a powerful tool for targeted therapeutic inhibition of cumulative oxidative stress and inflammation and protection of telomere attrition associated with smoking. The longitudinal studies of the clinical

  10. CDC Vital Signs: Preventing Repeat Teen Births

    Science.gov (United States)

    ... file Error processing SSI file Preventing Repeat Teen Births Recommend on Facebook Tweet Share Compartir On this ... Too many teens, ages 15–19, have repeat births. Nearly 1 in 5 births to teens, ages ...

  11. Comparison on three classification techniques for sex estimation from the bone length of Asian children below 19 years old: an analysis using different group of ages.

    Science.gov (United States)

    Darmawan, M F; Yusuf, Suhaila M; Kadir, M R Abdul; Haron, H

    2015-02-01

    Sex estimation is used in forensic anthropology to assist the identification of individual remains. However, the estimation techniques tend to be unique and applicable only to a certain population. This paper analyzed sex estimation on living individual child below 19 years old using the length of 19 bones of left hand applied for three classification techniques, which were Discriminant Function Analysis (DFA), Support Vector Machine (SVM) and Artificial Neural Network (ANN) multilayer perceptron. These techniques were carried out on X-ray images of the left hand taken from an Asian population data set. All the 19 bones of the left hand were measured using Free Image software, and all the techniques were performed using MATLAB. The group of age "16-19" years old and "7-9" years old were the groups that could be used for sex estimation with as their average of accuracy percentage was above 80%. ANN model was the best classification technique with the highest average of accuracy percentage in the two groups of age compared to other classification techniques. The results show that each classification technique has the best accuracy percentage on each different group of age. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Does cellular aging relate to patterns of allostasis? An examination of basal and stress reactive HPA axis activity and telomere length.

    Science.gov (United States)

    Tomiyama, A Janet; O'Donovan, Aoife; Lin, Jue; Puterman, Eli; Lazaro, Alanie; Chan, Jessica; Dhabhar, Firdaus S; Wolkowitz, Owen; Kirschbaum, Clemens; Blackburn, Elizabeth; Epel, Elissa

    2012-04-12

    Long-term exposure to stress and its physiological mediators, in particular cortisol, may lead to impaired telomere maintenance. In this study, we examine if greater cortisol responses to an acute stressor and/or dysregulated patterns of daily cortisol secretion are associated with shorter telomere length. Twenty-three postmenopausal women comprising caregivers for dementia partners (n=14) and age- and BMI-matched non-caregivers provided home sampling of cortisol-saliva samples at waking, 30 min after waking, and bedtime, and a 12-hour overnight urine collection. They were also exposed to an acute laboratory stressor throughout which they provided saliva samples. Peripheral blood mononuclear cells were isolated from a fasting blood sample and assayed for telomere length. As hypothesized, greater cortisol responses to the acute stressor were associated with shorter telomeres, as were higher overnight urinary free cortisol levels and flatter daytime cortisol slopes. While robust physiological responses to acute stress serve important functions, the long-term consequences of frequent high stress reactivity may include accelerated telomere shortening.

  13. Effects of parental nativity and length of stay in the US on fruit and vegetable intake among WIC-enrolled preschool-aged children.

    Science.gov (United States)

    Chaparro, M P; Langellier, B A; Wang, M C; Koleilat, M; Whaley, S E

    2015-04-01

    Exposure to US culture is negatively associated with fruits and vegetables (F&V) intake. Our goal was to investigate how parent's nativity and length of stay in the US influences preschoolers' F&V intake. We analyzed survey data from 2,352 children, aged 36-60 months, who participate in the Supplemental Nutrition Program for Women, Infants and Children (WIC) in Los Angeles County. Using multiple linear regression, we examined children's F&V intake by parent's nativity and years in the US, adjusting for possible confounders. Children of foreign born parents who had lived in the US for US born parents and of foreign born parents who had lived in the US for ≥10 years. Children of newer immigrant families may be at greater risk for consuming poor-quality diets. Research to identify determinants of poor diet quality among children of immigrant families may increase the effectiveness of WIC in addressing this population's nutritional needs.

  14. Some remarks on the influence of temperature-variations, non-linearities, repeatability and ageing on modal-analysis for structural health monitoring of real bridges

    Directory of Open Access Journals (Sweden)

    Maas Stefan

    2015-01-01

    Full Text Available Structural Health Monitoring (SHM intends to identify damage by changes of characteristics as for instance the modal parameters. The eigenfrequencies, mode-shapes and damping-values are either directly used as damage indicators or the changes of derived parameters are analysed, such as e.g. flexibilities or updated finite element models. One common way is a continuous monitoring under environmental excitation forces, such as wind or traffic, i.e. the so-called output-only modal analysis. Alternatively, a forced measured external excitation in distinct time-intervals may be used for input-output modal analysis. Both methods are limited by the precision or the repeatability under real-life conditions at site. The paper will summarize several field tests of artificially step-by-step damaged bridges prior to their final demolishment and it will show the changes of eigenfrequencies due to induced artificial damage. Additionally, some results of a monitoring campaign of a healthy bridge in Luxembourg are presented. Reinforced concrete shows non-linear behaviour in the sense that modal parameters depend on the excitation force amplitude, i.e. higher forces lead often to lower eigenfrequencies than smaller forces. Furthermore, the temperature of real bridges is neither constant in space nor in time, while for instance the stiffness of asphalt is strongly dependant on it. Finally, ageing as such can also change a bridge’s stiffness and its modal parameters, e.g. because creep and shrinkage of concrete or ageing of elastomeric bearing pads influence their modulus of elasticity. These effects cannot be considered as damage, though they influence the measurement of modal parameters and hinder damage detection.

  15. Deployment Repeatability

    Science.gov (United States)

    2016-04-01

    controlled to great precision, but in a Cubesat , there may be no attitude determination at all. Such a Cubesat might treat sun angle and tumbling rates as...could be sensitive to small differences in motor controller timing. In these cases, the analyst might choose to model the entire deployment path, with...knowledge of the material damage model or motor controller timing precision. On the other hand, if many repeated and environmentally representative

  16. CTG trinucleotide repeat "big jumps": large expansions, small mice.

    Directory of Open Access Journals (Sweden)

    Mário Gomes-Pereira

    2007-04-01

    Full Text Available Trinucleotide repeat expansions are the genetic cause of numerous human diseases, including fragile X mental retardation, Huntington disease, and myotonic dystrophy type 1. Disease severity and age of onset are critically linked to expansion size. Previous mouse models of repeat instability have not recreated large intergenerational expansions ("big jumps", observed when the repeat is transmitted from one generation to the next, and have never attained the very large tract lengths possible in humans. Here, we describe dramatic intergenerational CTG*CAG repeat expansions of several hundred repeats in a transgenic mouse model of myotonic dystrophy type 1, resulting in increasingly severe phenotypic and molecular abnormalities. Homozygous mice carrying over 700 trinucleotide repeats on both alleles display severely reduced body size and splicing abnormalities, notably in the central nervous system. Our findings demonstrate that large intergenerational trinucleotide repeat expansions can be recreated in mice, and endorse the use of transgenic mouse models to refine our understanding of triplet repeat expansion and the resulting pathogenesis.

  17. C9ORF72 repeat expansion in Australian and Spanish frontotemporal dementia patients.

    Directory of Open Access Journals (Sweden)

    Carol Dobson-Stone

    Full Text Available A hexanucleotide repeat expansion in C9ORF72 has been established as a common cause of frontotemporal dementia (FTD. However, the minimum repeat number necessary for disease pathogenesis is not known. The aims of our study were to determine the frequency of the C9ORF72 repeat expansion in two FTD patient collections (one Australian and one Spanish, combined n = 190, to examine C9ORF72 expansion allele length in a subset of FTD patients, and to examine C9ORF72 allele length in 'non-expansion' patients (those with <30 repeats. The C9ORF72 repeat expansion was detected in 5-17% of patients (21-41% of familial FTD patients. For one family, the expansion was present in the proband but absent in the mother, who was diagnosed with dementia at age 68. No association was found between C9ORF72 non-expanded allele length and age of onset and in the Spanish sample mean allele length was shorter in cases than in controls. Southern blotting analysis revealed that one of the nine 'expansion-positive' patients examined, who had neuropathologically confirmed frontotemporal lobar degeneration with TDP-43 pathology, harboured an 'intermediate' allele with a mean size of only ∼65 repeats. Our study indicates that the C9ORF72 repeat expansion accounts for a significant proportion of Australian and Spanish FTD cases. However, C9ORF72 allele length does not influence the age at onset of 'non-expansion' FTD patients in the series examined. Expansion of the C9ORF72 allele to as little as ∼65 repeats may be sufficient to cause disease.

  18. Flame Length

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — Flame length was modeled using FlamMap, an interagency fire behavior mapping and analysis program that computes potential fire behavior characteristics. The tool...

  19. Childhood Personality, Betrayal Trauma, and Leukocyte Telomere Length in Adulthood: A Lifespan Perspective on Conscientiousness and Betrayal Traumas as Predictors of a Biomarker of Cellular Aging.

    Science.gov (United States)

    Edmonds, Grant W; Hampson, Sarah E; Côté, Hélène C F; Hill, Patrick L; Klest, Bridget

    2016-01-01

    Conscientiousness is associated with longevity. As such, identifying the biological pathways linking personality to mortality is important. This study employs longitudinal data spanning >40 years to test prospective associations with Leukocyte Telomere Length (LTL), a potential marker of cellular aging. Because telomeres shorten over time, and are sensitive to oxidative stress, shorter LTL may reflect cumulative damage associated with negative health behaviors and past stressful events. We investigated childhood conscientiousness as a protective factor, expecting an association with longer LTL in adulthood, possibly reflecting slower LTL shortening. Potential lifespan pathways involving childhood trauma, smoking behaviors, and Body Mass Index (BMI) were explored. Childhood conscientiousness showed a small raw association with LTL (r = .08, p = .04), although this effect did not persist when controlling for age and sex. Despite this lack of a direct effect on LTL, we detected an indirect effect operating jointly through BMI and smoking. Higher rates of childhood betrayal trauma were associated with shorter LTL. Contrary to our hypothesis that conscientiousness would buffer this effect, we found evidence for an interaction with childhood betrayal traumas where the association between childhood betrayal traumas and LTL was larger for those higher on conscientiousness in childhood.

  20. Role of TERRA in the regulation of telomere length.

    Science.gov (United States)

    Wang, Caiqin; Zhao, Li; Lu, Shiming

    2015-01-01

    Telomere dysfunction is closely associated with human diseases such as cancer and ageing. Inappropriate changes in telomere length and/or structure result in telomere dysfunction. Telomeres have been considered to be transcriptionally silent, but it was recently demonstrated that mammalian telomeres are transcribed into telomeric repeat-containing RNA (TERRA). TERRA, a long non-coding RNA, participates in the regulation of telomere length, telomerase activity and heterochromatinization. The correct regulation of telomere length may be crucial to telomeric homeostasis and functions. Here, we summarize recent advances in our understanding of the crucial role of TERRA in the maintenance of telomere length, with focus on the variety of mechanisms by which TERRA is involved in the regulation of telomere length. This review aims to enable further understanding of how TERRA-targeted drugs can target telomere-related diseases.

  1. Effects of prenatal Leydig cell function on the ratio of the second to fourth digit lengths in school-aged children.

    Directory of Open Access Journals (Sweden)

    Takahiko Mitsui

    Full Text Available Prenatal sex hormones can induce abnormalities in the reproductive system and adversely impact on genital development. We investigated whether sex hormones in cord blood influenced the ratio of the second to fourth digit lengths (2D/4D in school-aged children. Of the 514 children who participated in a prospective cohort study on birth in Sapporo between 2002 and 2005, the following sex hormone levels were measured in 294 stored cord blood samples (135 boys and 159 girls; testosterone (T, estradiol (E, progesterone, LH, FSH, inhibin B, and insulin-like factor 3 (INSL3. A total of 350 children, who were of school age and could be contacted for this survey, were then requested via mail to send black-and-white photocopies of the palms of both the left and right hands. 2D/4D was calculated in 190 children (88 boys and 102 girls using photocopies and derived from participants with the characteristics of older mothers, a higher annual household income, higher educational level, and fewer smokers among family members. 2D/4D was significantly lower in males than in females (p<0.01. In the 294 stored cord blood samples, T, T/E, LH, FSH, Inhibin B, and INSL3 levels were significantly higher in samples collected from males than those from females. A multivariate regression model revealed that 2D/4D negatively correlated with INSL3 in males and was significantly higher in males with <0.32 ng/mL of INSL3 (p<0.01. No correlations were observed between other hormones and 2D/4D. In conclusion, 2D/4D in school-aged children, which was significantly lower in males than in females, was affected by prenatal Leydig cell function.

  2. Intergenerational and striatal CAG repeat instability in Huntington's disease knock-in mice involve different DNA repair genes.

    Science.gov (United States)

    Dragileva, Ella; Hendricks, Audrey; Teed, Allison; Gillis, Tammy; Lopez, Edith T; Friedberg, Errol C; Kucherlapati, Raju; Edelmann, Winfried; Lunetta, Kathryn L; MacDonald, Marcy E; Wheeler, Vanessa C

    2009-01-01

    Modifying the length of the Huntington's disease (HD) CAG repeat, the major determinant of age of disease onset, is an attractive therapeutic approach. To explore this we are investigating mechanisms of intergenerational and somatic HD CAG repeat instability. Here, we have crossed HD CAG knock-in mice onto backgrounds deficient in mismatch repair genes, Msh3 and Msh6, to discern the effects on CAG repeat size and disease pathogenesis. We find that different mechanisms predominate in inherited and somatic instability, with Msh6 protecting against intergenerational contractions and Msh3 required both for increasing CAG length and for enhancing an early disease phenotype in striatum. Therefore, attempts to decrease inherited repeat size may entail a full understanding of Msh6 complexes, while attempts to block the age-dependent increases in CAG size in striatal neurons and to slow the disease process will require a full elucidation of Msh3 complexes and their function in CAG repeat instability.

  3. Studies of the CAG repeat in the Machado-Joseph disease gene in Taiwan.

    Science.gov (United States)

    Hsieh, M; Tsai, H F; Lu, T M; Yang, C Y; Wu, H M; Li, S Y

    1997-08-01

    Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration characterized by cerebellar ataxia and pyramidal signs associated in varying degrees with a dystonic-rigid extrapyramidal syndrome or peripheral amyotrophy. Unstable CAG trinucleotide repeat expansion in the MJD gene on the long arm of chromosome 14 has been identified as the pathological mutation for MJD. While investigating the distribution of CAG repeat lengths of the MJD gene in Taiwan's population, we have identified 18 MJD-affected patients and 12 at-risk individuals in seven families. In addition, we have analyzed the range of CAG repeat lengths in 96 control individuals. The CAG repeat number ranged from 13 to 44 in the controls and 72-85 in the affected and at-risk individuals. Our results indicated that the CAG repeat number was inversely correlated with the age of onset. The differences in CAG repeat length between parent and child and between siblings are greater with paternal transmission than maternal transmission. Our data show a tendency towards the phenomenon of anticipation in the MJD families but do not support unidirectional expansion of CAG repeats during transmission. We also demonstrated that PCR amplification of the CAG repeats in the MJD gene from villous DNA was possible and might prove useful as a diagnostic tool for affected families in the future.

  4. Analysis of CAG repeats in IT15 gene in Spanish population

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez, A.; Castellvi-Pel, S.; Mila, M. [Hospital Clinic i Provincial de Parcelons (Spain)] [and others

    1994-09-01

    Huntington`s disease (HD) is an autosomal dominant neurodegenerative disorder characterized by involuntary movements, and cognitive and affective changes. HD has a prevalence of 1 in 10,000 individuals in most populations of European origin. The IT15 gene is responsible for HD as it contains a highly polymorphic, unstable (CAG) repeated sequence that is abnormally expanded in HD chromosomes. The IT15 (CAG)n stretch was analyzed in 100 members (50 affected individuals, 40 asymptomatic at risk for HD, and 10 unaffected members) of 50 HD families, and 50 individuals of the general Spanish population. Expansion of the CAG repeat sequence was found in 45 affected members and 14 individuals at risk, with a repeat length of 40 to 85 repeat units. The range of the polymorphic CAG repeat in normal chromosomes was between 11 and 31 repeat units. In the families with several affected members, we found increases of the repeat length in the least generation. Inverse correlation was found between the age of onset and the length of the CAG repeat; the analysis showed also parental male bias. Presymptomatic analysis of HD has been considerably enhanced with the CAG mutation study.

  5. Sex-specific mediation effect of the right fusiform face area volume on the association between variants in repeat length of AVPR1A RS3 and altruistic behavior in healthy adults.

    Science.gov (United States)

    Wang, Junping; Qin, Wen; Liu, Feng; Liu, Bing; Zhou, Yuan; Jiang, Tianzi; Yu, Chunshui

    2016-07-01

    Microsatellite variants in the arginine vasopressin receptor 1A gene (AVPR1A) RS3 have been associated with normal social behaviors variation and autism spectrum disorders (ASDs) in a sex-specific manner. However, neural mechanisms underlying these associations remain largely unknown. We hypothesized that AVPR1A RS3 variants affect altruistic behavior by modulating the gray matter volume (GMV) of specific brain regions in a sex-specific manner. We investigated 278 young healthy adults using the Dictator Game to assess altruistic behavior. All subjects were genotyped and main effect of AVPR1A RS3 repeat polymorphisms and interaction of genotype-by-sex on the GMV were assessed in a voxel-wise manner. We observed that male subjects with relatively short repeats allocated less money to others and exhibited a significantly smaller GMV in the right fusiform face area (FFA) compared with male long homozygotes. In male subjects, the GMV of the right FFA exhibited a significant positive correlation with altruistic behavior. A mixed mediation and moderation analysis further revealed both a significant mediation effect of the GMV of the right FFA on the association between AVPR1A RS3 repeat polymorphisms and allocation sums and a significant moderation effect of sex (only in males) on the mediation effect. Post hoc analysis showed that the GMV of the right FFA was significantly smaller in male subjects carrying allele 426 than in non-426 carriers. These results suggest that the GMV of the right FFA may be a potential mediator whereby the genetic variants in AVPR1A RS3 affect altruistic behavior in healthy male subjects. Hum Brain Mapp 37:2700-2709, 2016. © 2016 Wiley Periodicals, Inc.

  6. Comparison of Birth-and Conception-Based Definitions of Postnatal Age in Developmental and Reproductive Rodent Toxicity Studies: lnfluence of Gestation Length on Measurements of Offspring Body Weight and Puberty in Controls

    Science.gov (United States)

    Most laboratories conducting developmental and reproductive toxicity studies in rodents assign age by defining postnatal day (PND) 0 or 1 as the day of birth (DOB); i.e., gestation length affects PND and the timing of postnatal measurements. Some laboratories, however, define age...

  7. Comparison of Birth-and Conception-Based Definitions of Postnatal Age in Developmental and Reproductive Rodent Toxicity Studies: lnfluence of Gestation Length on Measurements of Offspring Body Weight and Puberty in Controls

    Science.gov (United States)

    Most laboratories conducting developmental and reproductive toxicity studies in rodents assign age by defining postnatal day (PND) 0 or 1 as the day of birth (DOB); i.e., gestation length affects PND and the timing of postnatal measurements. Some laboratories, however, define age...

  8. Telomere length and depression

    DEFF Research Database (Denmark)

    Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Rode, Line

    2016-01-01

    BACKGROUND: Depression has been cross-sectionally associated with short telomeres as a measure of biological age. However, the direction and nature of the association is currently unclear. AIMS: We examined whether short telomere length is associated with depression cross-sectionally as well...... as prospectively and genetically. METHOD: Telomere length and three polymorphisms, TERT, TERC and OBFC1, were measured in 67 306 individuals aged 20-100 years from the Danish general population and associated with register-based attendance at hospital for depression and purchase of antidepressant medication....... RESULTS: Attendance at hospital for depression was associated with short telomere length cross-sectionally, but not prospectively. Further, purchase of antidepressant medication was not associated with short telomere length cross-sectionally or prospectively. Mean follow-up was 7.6 years (range 0...

  9. 4p16.3 haplotype modifying age at onset of Huntington disease

    DEFF Research Database (Denmark)

    Nørremølle, A; Budtz-Jørgensen, E; Fenger, K

    2009-01-01

    Huntington disease (HD) is caused by an expanded CAG repeat sequence in the HD gene. Although the age at onset is correlated to the CAG repeat length, this correlation only explains approximately half of the variation in onset age. Less variation between siblings indicates that the variation is, ...

  10. Length of CAG repeat in exon 1 of the androgen receptor gene is associated with the development of acne%雄激素受体基因第一外显子CAG重复序列长度多态性与痤疮的相关性

    Institute of Scientific and Technical Information of China (English)

    庞莹; 姜弈; 魏华臣; 陈洪铎; 何春涤; 刘勇; 朱红; 魏彬; 王凯波; 赵宁; 王雅坤; 肖汀

    2008-01-01

    目的 探讨人雄激素受体基因第一外显子CAG重复序列长度多态性与痤疮发生之间的关系.方法 研究对象为中国东北地区238例痤疮患者和207例健康对照,抽取外周血后分离纯化出基因组DNA,采用微卫星扫描(STRs)方法分析CAG重复序列的多态性.结果 男性病例组和对照组的CAG重复均数分别为22.70±3.09和23.48±2.83,两组之间差异有统计学意义(P=0.046);将对照组中CAG重复次数的中位数23作为分割点分组比较,长/短CAG片段在男性病例和对照中的分布差异有统计学意义,携带有CAG短片段的男性较携带CAG长片段的男性患痤疮的风险性明显增加(OR值2.07;95%可信限为1.21~3.54).女性病例组和对照组的CAG重复均数分别为23.41±2.87和23.85±0.21,两组之间差异无统计学意义(P=0.115);按中位数分组比较长/短CAG片段在女性病例和对照中的分布差异有统计学意义,携带有CAG短片段的女性患痤疮的风险性明显增加(P=0.013,OR值2.05;95%可信限为1.18~3.56).结论 雄激素受体基因第一外显子CAG的重复次数与中国东北地区痤疮的发生有关,CAG重复次数少的男性个体患痤疮的风险性增加,雄激素受体基因第一外显子CAG的重复次数可作为痤疮的遗传易感标志之一.%Objective To investigate the relationship of CAG repeat length polymorphism in the androgen receptor(AR)gene to the development of acne.Methods A total of 238 patients with ache vulgaris and 207 healthy human controls in Northeast China were included in this study.Genomic DNA was isolated and purified from the blood of these subjects.The CAG repeat lengths in the AR gene were analyzed by somatic microsatellites (STRs).Results A significant difference was found in the CAG repeat number between the male acne Patients(22.70±3.09)and male controls(23.48±2.83,P=0.046),but not between the female cases and controls(23.41±2.87 versus 23.85±0.21.P=0.12).In order to assess the

  11. Nonparametric modeling and analysis of association between Huntington's disease onset and CAG repeats.

    Science.gov (United States)

    Ma, Yanyuan; Wang, Yuanjia

    2014-04-15

    Huntington's disease (HD) is a neurodegenerative disorder with a dominant genetic mode of inheritance caused by an expansion of CAG repeats on chromosome 4. Typically, a longer sequence of CAG repeat length is associated with increased risk of experiencing earlier onset of HD. Previous studies of the association between HD onset age and CAG length have favored a logistic model, where the CAG repeat length enters the mean and variance components of the logistic model in a complex exponential-linear form. To relax the parametric assumption of the exponential-linear association to the true HD onset distribution, we propose to leave both mean and variance functions of the CAG repeat length unspecified and perform semiparametric estimation in this context through a local kernel and backfitting procedure. Motivated by including family history of HD information available in the family members of participants in the Cooperative Huntington's Observational Research Trial (COHORT), we develop the methodology in the context of mixture data, where some subjects have a positive probability of being risk free. We also allow censoring on the age at onset of disease and accommodate covariates other than the CAG length. We study the theoretical properties of the proposed estimator and derive its asymptotic distribution. Finally, we apply the proposed methods to the COHORT data to estimate the HD onset distribution using a group of study participants and the disease family history information available on their family members.

  12. Telomere length correlations among somatic tissues in adult zebra finches.

    Directory of Open Access Journals (Sweden)

    Sophie Reichert

    Full Text Available Telomeres are repetitive non coding DNA sequences located at the end of eukaryotic chromosomes, which maintain the integrity of the genome by hiding the chromosome ends from being recognised as double stranded breaks. Telomeres are emerging as biomarkers for ageing and survival, and are susceptible to reflect different individual life history trajectories. In particular, the telomere length with which one starts in life has been shown to be linked with individual life-long survival, suggesting that telomere dynamics can be a proxy for individual fitness and thereby be implicated in evolutionary trade-offs. As a consequence, an increasing number of studies were conducted on telomeres in the fields of ecology and evolutionary biology, in which telomere length was almost exclusively measured from blood samples. However, not only do the number of repeats of the telomeric sequences vary among species, but also within species with great inter-individual telomere lengths variability with age, tissues, and chromosomes. This raises the issue of the exact biological meaning of telomere measurement in blood cells and stimulated the study of the correlation of telomere lengths among tissues over age. By measuring telomere length in adult zebra finches (Taeniopygia guttata in different somatic tissues displaying variable cell turnovers (bone marrow, brain, spleen, pectoral muscle, heart, liver and in red blood cells, we checked that the measure of telomere length in red blood cells is related to telomere lengths in the other tissues. Here we show significant relationships between the telomere lengths of red blood cells and several somatic tissues at adulthood. As red blood cells are easily accessible and suitable for the longitudinal monitoring of the individual rate of telomere loss, our study confirms that telomere length measured in red blood cells could serve as a surrogate for telomere length in the whole avian organism.

  13. Hsp72 is present in plasma from Holstein-Friesian dairy cattle, and the concentration level is repeatable across days and age classes

    OpenAIRE

    Nygaard Kristensen, Torsten; Løvendahl, Peter; Berg, Peer; Loeschcke, Volker

    2004-01-01

    Although heat shock proteins (Hsps) are primarily considered as being intracellular, this study identified the presence of Hsp72 in plasma from female Holstein-Friesian dairy cattle. Plasma samples were collected from the same animals at different ages and on different days after calving and accordingly divided into 5 age classes. The age classes were calves less than 235 days of age, young heifers between 235 and 305 days of age, older heifers between 305 and 560 days of age, cows early in l...

  14. "Which Mouse Kissed the Frog?" Effects of Age of Onset, Length of Exposure, and Knowledge of Case Marking on the Comprehension of "Wh"-Questions in German-Speaking Simultaneous and Early Sequential Bilingual Children

    Science.gov (United States)

    Roesch, Anne Dorothee; Chondrogianni, Vasiliki

    2016-01-01

    Studies examining age of onset (AoO) effects in childhood bilingualism have provided mixed results as to whether early sequential bilingual children (eL2) differ from simultaneous bilingual children (2L1) and L2 children on the acquisition of morphosyntax. Differences between the three groups have been attributed to other factors such as length of…

  15. "Which Mouse Kissed the Frog?" Effects of Age of Onset, Length of Exposure, and Knowledge of Case Marking on the Comprehension of "Wh"-Questions in German-Speaking Simultaneous and Early Sequential Bilingual Children

    Science.gov (United States)

    Roesch, Anne Dorothee; Chondrogianni, Vasiliki

    2016-01-01

    Studies examining age of onset (AoO) effects in childhood bilingualism have provided mixed results as to whether early sequential bilingual children (eL2) differ from simultaneous bilingual children (2L1) and L2 children on the acquisition of morphosyntax. Differences between the three groups have been attributed to other factors such as length of…

  16. Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

    Science.gov (United States)

    Langfelder, Peter; Cantle, Jeffrey P; Chatzopoulou, Doxa; Wang, Nan; Gao, Fuying; Al-Ramahi, Ismael; Lu, Xiao-Hong; Ramos, Eliana Marisa; El-Zein, Karla; Zhao, Yining; Deverasetty, Sandeep; Tebbe, Andreas; Schaab, Christoph; Lavery, Daniel J; Howland, David; Kwak, Seung; Botas, Juan; Aaronson, Jeffrey S; Rosinski, Jim; Coppola, Giovanni; Horvath, Steve; Yang, X William

    2016-04-01

    To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo.

  17. Telomere length in bipolar disorder and lithium response.

    Science.gov (United States)

    Squassina, Alessio; Pisanu, Claudia; Corbett, Nathan; Alda, Martin

    2017-06-01

    Telomeres consist of exanucleotide tandem repeats and proteins complexes at the end of chromosome ends. Telomeres shorten at each cell division, and as such telomere length is a marker of cellular age. Accelerated telomere shortening and cell senescence have been associated with a number of chronic medical conditions, including psychiatric disorders, where increased prevalence of age-related disorders and shorter telomere length have been reported. Shorter telomeres in psychiatric patients are thought to be the consequence of allostatic load, consisting in the overactivation of allostatic systems due to chronic exposure to severe medical conditions and failure to adapt to chronic stressful stimuli. Most of the studies on telomere length in psychiatry have focused on major depressive disorder, but recent findings have shown shorter leukocyte telomere length in bipolar disorder patients and suggested that lithium may counteract telomeres shortening. These findings provided new insights into the pathophysiology of bipolar disorder and the mechanism of action of lithium. In this review we will present findings from the literature on telomere length in bipolar disorder, with a specific focus on lithium. We will also discuss advances and limitations of published work as well as methodological issues and potential confounding factors that should be taken into account when designing research protocols to study telomere length. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  18. Telomere Length and Mortality

    DEFF Research Database (Denmark)

    Kimura, Masayuki; Hjelmborg, Jacob V B; Gardner, Jeffrey P

    2008-01-01

    telomeres predicted the death of the first co-twin better than the mTRFL did (mTRFL: 0.56, 95% confidence interval (CI): 0.49, 0.63; mTRFL(50): 0.59, 95% CI: 0.52, 0.66; mTRFL(25): 0.59, 95% CI: 0.52, 0.66; MTRFL: 0.60, 95% CI: 0.53, 0.67). The telomere-mortality association was stronger in years 3-4 than......Leukocyte telomere length, representing the mean length of all telomeres in leukocytes, is ostensibly a bioindicator of human aging. The authors hypothesized that shorter telomeres might forecast imminent mortality in elderly people better than leukocyte telomere length. They performed mortality...... analysis in 548 same-sex Danish twins (274 pairs) aged 73-94 years, of whom 204 pairs experienced the death of one or both co-twins during 9-10 years of follow-up (1997-2007). From the terminal restriction fragment length (TRFL) distribution, the authors obtained the mean TRFL (mTRFL) and the mean values...

  19. Mining of simple sequence repeats in the Genome of Gentianaceae

    Directory of Open Access Journals (Sweden)

    R Sathishkumar

    2011-01-01

    Full Text Available Simple sequence repeats (SSRs or short tandem repeats are short repeat motifs that show high level of length polymorphism due to insertion or deletion mutations of one or more repeat types. Here, we present the detection and abundance of microsatellites or SSRs in nucleotide sequences of Gentianaceae family. A total of 545 SSRs were mined in 4698 nucleotide sequences downloaded from the National Center for Biotechnology Information (NCBI. Among the SSR sequences, the frequency of repeat type was about 429 -mono repeats, 99 -di repeats, 15 -tri repeats, and 2 --hexa repeats. Mononucleotide repeats were found to be abundant repeat types, about 78%, followed by dinucleotide repeats (18.16% among the SSR sequences. An attempt was made to design primer pairs for 545 identified SSRs but these were found only for 169 sequences.

  20. Repeat-until-success quantum repeaters

    Science.gov (United States)

    Bruschi, David Edward; Barlow, Thomas M.; Razavi, Mohsen; Beige, Almut

    2014-09-01

    We propose a repeat-until-success protocol to improve the performance of probabilistic quantum repeaters. Conventionally, these rely on passive static linear-optics elements and photodetectors to perform Bell-state measurements (BSMs) with a maximum success rate of 50%. This is a strong impediment for entanglement swapping between distant quantum memories. Every time a BSM fails, entanglement needs to be redistributed between the corresponding memories in the repeater link. The key ingredients of our scheme are repeatable BSMs. Under ideal conditions, these turn probabilistic quantum repeaters into deterministic ones. Under realistic conditions, our protocol too might fail. However, using additional threshold detectors now allows us to improve the entanglement generation rate by almost orders of magnitude, at a nominal distance of 1000 km, compared to schemes that rely on conventional BSMs. This improvement is sufficient to make the performance of our scheme comparable to the expected performance of some deterministic quantum repeaters.

  1. Methylation at global LINE-1 repeats in human blood are affected by gender but not by age or natural hormone cycles.

    Directory of Open Access Journals (Sweden)

    Osman El-Maarri

    Full Text Available Previously, we reported on inter-individual and gender specific variations of LINE-1 methylation in healthy individuals. In this study, we investigated whether this variability could be influenced by age or sex hormones in humans. To this end, we studied LINE-1 methylation in vivo in blood-derived DNA from individuals aged 18 to 64 years and from young healthy females at various hormone levels during the menstrual cycle. Our results show that no significant association with age was observed. However, the previously reported increase of LINE-1 methylation in males was reconfirmed. In females, although no correlation between LINE-1 or Alu methylation and hormone levels was observed, a significant stable individual specific level of methylation was noted. In vitro results largely confirmed these findings, as neither estrogen nor dihydrotestosterone affected LINE-1 or Alu methylation in Hek293T, HUVEC, or MDA-kb2 cell lines. In contrast, a decrease in methylation was observed in estrogen-treated T47-Kbluc cell lines strongly expressing estrogen receptor. The very low expression of estrogen receptor in blood cells could explain the observed insensitivity of methylation at LINE-1 to natural hormonal variations in females. In conclusion, neither natural cycle of hormones nor age has a detectable effect on the LINE-1 methylation in peripheral blood cells, while gender remains an important factor.

  2. Etiological Role and Repeated Infections of Sapovirus among Children Aged Less than 2 Years in a Cohort Study in a Peri-urban Community of Peru.

    Science.gov (United States)

    Liu, Xiaofang; Jahuira, Helena; Gilman, Robert H; Alva, Alicia; Cabrera, Lilia; Okamoto, Michiko; Xu, Hang; Windle, Henry J; Kelleher, Dermot; Varela, Marco; Verastegui, Manuela; Calderon, Maritza; Sanchez, Gerardo; Sarabia, Vanessa; Ballard, Sarah B; Bern, Caryn; Mayta, Holger; Crabtree, Jean E; Cama, Vitaliano; Saito, Mayuko; Oshitani, Hitoshi

    2016-06-01

    Human sapovirus has been shown to be one of the most important etiologies in pediatric patients with acute diarrhea. However, very limited data are available about the causative roles and epidemiology of sapovirus in community settings. A nested matched case-control study within a birth cohort study of acute diarrhea in a peri-urban community in Peru from 2007 to 2010 was conducted to investigate the attributable fraction (AF) and genetic diversity of sapovirus. By quantitative reverse transcription-real-time PCR (qPCR) sapovirus was detected in 12.4% (37/299) of diarrheal and 5.7% (17/300) of nondiarrheal stools (P = 0.004). The sapovirus AF (7.1%) was higher in the second year (13.2%) than in the first year (1.4%) of life of children. Ten known genotypes and one novel cluster (n = 5) within four genogroups (GI, GII, GIV, and GV) were identified by phylogenetic analysis of a partial VP1 gene. Further sequence analysis of the full VP1 gene revealed a possible novel genotype, tentatively named GII.8. Notably, symptomatic reinfections with different genotypes within the same (n = 3) or different (n = 5) genogroups were observed in eight children. Sapovirus exhibited a high attributable burden for acute gastroenteritis, especially in the second year of life, of children in a Peruvian community. Further large-scale studies are needed to understand better the global burden, genetic diversity, and repeated infections of sapovirus. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  3. Pulse Wave Velocity as Marker of Preclinical Arterial Disease: Reference Levels in a Uruguayan Population Considering Wave Detection Algorithms, Path Lengths, Aging, and Blood Pressure

    Directory of Open Access Journals (Sweden)

    Ignacio Farro

    2012-01-01

    Full Text Available Carotid-femoral pulse wave velocity (PWV has emerged as the gold standard for non-invasive evaluation of aortic stiffness; absence of standardized methodologies of study and lack of normal and reference values have limited a wider clinical implementation. This work was carried out in a Uruguayan (South American population in order to characterize normal, reference, and threshold levels of PWV considering normal age-related changes in PWV and the prevailing blood pressure level during the study. A conservative approach was used, and we excluded symptomatic subjects; subjects with history of cardiovascular (CV disease, diabetes mellitus or renal failure; subjects with traditional CV risk factors (other than age and gender; asymptomatic subjects with atherosclerotic plaques in carotid arteries; patients taking anti-hypertensives or lipid-lowering medications. The included subjects (n=429 were categorized according to the age decade and the blood pressure levels (at study time. All subjects represented the “reference population”; the group of subjects with optimal/normal blood pressures levels at study time represented the “normal population.” Results. Normal and reference PWV levels were obtained. Differences in PWV levels and aging-associated changes were obtained. The obtained data could be used to define vascular aging and abnormal or disease-related arterial changes.

  4. Remarkable selective constraints on exonic dinucleotide repeats.

    Science.gov (United States)

    Haasl, Ryan J; Payseur, Bret A

    2014-09-01

    Long dinucleotide repeats found in exons present a substantial mutational hazard: mutations at these loci occur often and generate frameshifts. Here, we provide clear and compelling evidence that exonic dinucleotides experience strong selective constraint. In humans, only 18 exonic dinucleotides have repeat lengths greater than six, which contrasts sharply with the genome-wide distribution of dinucleotides. We genotyped each of these dinucleotides in 200 humans from eight 1000 Genomes Project populations and found a near-absence of polymorphism. More remarkably, divergence data demonstrate that repeat lengths have been conserved across the primate phylogeny in spite of what is likely considerable mutational pressure. Coalescent simulations show that even a very low mutation rate at these loci fails to explain the anomalous patterns of polymorphism and divergence. Our data support two related selective constraints on the evolution of exonic dinucleotides: a short-term intolerance for any change to repeat length and a long-term prevention of increases to repeat length. In general, our results implicate purifying selection as the force that eliminates new, deleterious mutants at exonic dinucleotides. We briefly discuss the evolution of the longest exonic dinucleotide in the human genome--a 10 x CA repeat in fibroblast growth factor receptor-like 1 (FGFRL1)--that should possess a considerably greater mutation rate than any other exonic dinucleotide and therefore generate a large number of deleterious variants. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  5. Prevalence of Huntington's disease gene CAG repeat alleles in sporadic amyotrophic lateral sclerosis patients.

    Science.gov (United States)

    Ramos, Eliana Marisa; Keagle, Pamela; Gillis, Tammy; Lowe, Patrick; Mysore, Jayalakshmi S; Leclerc, Ashley Lyn; Ratti, Antonia; Ticozzi, Nicola; Gellera, Cinzia; Gusella, James F; Silani, Vincenzo; Alonso, Isabel; Brown, Robert H; MacDonald, Marcy E; Landers, John E

    2012-05-01

    A higher prevalence of intermediate ataxin-2 CAG repeats in amyotrophic lateral sclerosis (ALS) patients has raised the possibility that CAG expansions in other polyglutamine disease genes could contribute to ALS neurodegeneration. We sought to determine whether expansions of the CAG repeat of the HTT gene that causes Huntington's disease, are associated with ALS. We compared the HTT CAG repeat length on a total of 3144 chromosomes from 1572 sporadic ALS patients and 4007 control chromosomes, and also tested its possible effects on ALS-specific parameters, such as age and site of onset and survival rate. Our results show that the CAG repeat in the HTT gene is not a risk factor for ALS nor modifies its clinical presentation. These findings suggest that distinct neuronal degeneration processes are involved in these two different neurodegenerative disorders.

  6. Genetic Contributors to Intergenerational CAG Repeat Instability in Huntington’s Disease Knock-In Mice

    Science.gov (United States)

    Neto, João Luís; Lee, Jong-Min; Afridi, Ali; Gillis, Tammy; Guide, Jolene R.; Dempsey, Stephani; Lager, Brenda; Alonso, Isabel; Wheeler, Vanessa C.; Pinto, Ricardo Mouro

    2017-01-01

    Huntington’s disease (HD) is a neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in exon 1 of the HTT gene. Longer repeat sizes are associated with increased disease penetrance and earlier ages of onset. Intergenerationally unstable transmissions are common in HD families, partly underlying the genetic anticipation seen in this disorder. HD CAG knock-in mouse models also exhibit a propensity for intergenerational repeat size changes. In this work, we examine intergenerational instability of the CAG repeat in over 20,000 transmissions in the largest HD knock-in mouse model breeding datasets reported to date. We confirmed previous observations that parental sex drives the relative ratio of expansions and contractions. The large datasets further allowed us to distinguish effects of paternal CAG repeat length on the magnitude and frequency of expansions and contractions, as well as the identification of large repeat size jumps in the knock-in models. Distinct degrees of intergenerational instability were observed between knock-in mice of six background strains, indicating the occurrence of trans-acting genetic modifiers. We also found that lines harboring a neomycin resistance cassette upstream of Htt showed reduced expansion frequency, indicative of a contributing role for sequences in cis, with the expanded repeat as modifiers of intergenerational instability. These results provide a basis for further understanding of the mechanisms underlying intergenerational repeat instability. PMID:27913616

  7. Predictors of Love Attitudes: The Contribution of Cultural Orientation, Gender Attachment Style, Relationship Length and Age in Participants From the UK and Hong Kong

    Directory of Open Access Journals (Sweden)

    Rebecca Smith

    2016-06-01

    Full Text Available The aim of this research was to explore whether a model including psychological predictors at the individual, interpersonal and cultural level could predict romantic attitudes. Attachment style, cultural orientation, gender, and relationship length were tested as predictors for each of the six love styles conceptualized by Lee (1977. Adults from Britain (N = 56 and Hong Kong (N = 52 who were in a romantic relationship completed four self-report measures; a demographic questionnaire, The Individualism and Collectivism Scale (IC-S, The Experiences in Close Relationship Scale-Short Form (ECR-S and The Love Attitude Scale short form (LAS. The model successfully predicted each love style and in one case (Mania accounted for 52% of the variance in this love style. Each love attitude had a different profile, and no one predictor dominated any one style which supports Lee’s original idea that the styles are qualitatively different.

  8. Influência da idade no tempo de internação e no grau evolutivo das apendicites agudas Age influence in hospital stay length and acute apendicitis evolution grade

    Directory of Open Access Journals (Sweden)

    Marcelo Wilson Rocha Almeida

    2006-10-01

    Full Text Available OBJETIVO: Comparar o grau evolutivo da apendicite determinada pela inspeção trans-operatória com o resultado anatomopatológico, e identificar alguma relação entre a idade, grau evolutivo da apendicite aguda e o tempo de internação hospitalar. MÉTODO: Análise retrospectiva dos prontuários de 199 pacientes submetidos a apendicectomia entre o período de outubro de 2003 a agosto de 2004, quanto à idade, sexo, tempo de internação e a fase do processo inflamatório segundo anatomopatológico das peças. RESULTADOS: A análise foi possível em 182 casos. Nestes pacientes, a distribuição quanto ao sexo mostrou maior incidência em homens, com 54,4% casos; a mediana da idade foi de 20 anos, sendo a faixa etária mais prevalente entre os 11-20 anos com 36,22% dos casos. A mediana do tempo de internação foi de três dias. Houve uma diferença significativa do tempo de internação de acordo com a faixa etária dos pacientes, sendo que os pacientes acima de 60 anos tiveram maior tempo de internação. O anatomopatológico evidenciou 73,62% casos de apendicite supurada, 13,73% apendicite branca, 7,14% gangrenosa, 4,49% catarral e 0,54% neoplásico, confirmando o diagnóstico de apendicite em 86,24%. O tempo de internação e a idade não foram significativamente diferentes entre os graus evolutivos da apendicite aguda. CONCLUSÕES: A apendicite aguda ocorre com maior freqüência nos pacientes jovens e do sexo masculino. Os pacientes idosos permanecem mais tempo internados, porém não houve diferença na idade nem tempo de internação em relação aos vários graus evolutivos da apendicite.BACKGROUND: To study appendicitis evolution grade in comparison with intraoperative inspection and pathological results. Also a relationship between age and hospital stay length is reviewed. METHODS: Retrospective analysis of 199 patients submitted to appendicectomy between October 2003 through August 2004 using: age, sex, length of hospital stay and

  9. Analysis and comparison of fish growth from small samples of length-at-age data : Detection of sexual dimorphism in Eurasian perch as an example

    NARCIS (Netherlands)

    Mooij, WM; Van Rooij, JM; Wijnhoven, S

    A relatively simple approach is presented for statistical analysis and comparison of fish growth patterns inferred from size-at-age data. It can be used for any growth model and small sample sizes. Bootstrapping is used to generate confidence regions for the model parameters and for size and growth

  10. The impact of repeated treatment with praziquantel of schistosomiasis in children under six years of age living in an endemic area for Schistosoma haematobium infection

    Directory of Open Access Journals (Sweden)

    T Mduluza

    2001-09-01

    Full Text Available Praziquantel was given every eight weeks for two years to children aged under six years of age, living in a Schistosoma haematobium endemic area. Infection with S. haematobium and haematuria were examined in urine and antibody profiles (IgA, IgE, IgM, IgG1, IgG2, IgG3, and IgG4 against S. haematobium adult worm and egg antigens were determined from sera collected before each treatment. Chemotherapy reduced infection prevalence and mean intensity from 51.8% and 110 eggs per 10 ml urine, respectively, before starting re-treatment programme to very low levels thereafter. Praziquantel is not accumulated after periodic administration in children. Immunoglobulin levels change during the course of treatment with a shift towards 'protective' mechanisms. The significant changes noted in some individuals were the drop in 'blocking' IgG2 and IgG4 whereas the 'protecting' IgA and IgG1 levels increased. The antibody profiles in the rest of the children remained generally unchanged throughout the study and no haematuria was observed after the second treatment. The removal of worms before production of large number of eggs, prevented the children from developing morbidity.

  11. CGG repeat in the FMR1 gene: Size matters

    NARCIS (Netherlands)

    R.A. Willemsen (Ralph); G.J. Levenga (Josien); B.A. Oostra (Ben)

    2011-01-01

    textabstractThe FMR1 gene contains a CGG repeat present in the 5'-untranslated region which can be unstable upon transmission to the next generation. The repeat is up to 55 CGGs long in the normal population. In patients with fragile X syndrome (FXS), a repeat length exceeding 200 CGGs (full

  12. Microdose acquisition in adolescent leg length discrepancy using a low-dose biplane imaging system

    DEFF Research Database (Denmark)

    Jensen, Janni; Mussmann, Bo Redder; Hjarbæk, John

    2017-01-01

    Background Children with leg length discrepancy often undergo repeat imaging. Therefore, every effort to reduce radiation dose is important. Using low dose preview images and noise reduction software rather than diagnostic images for length measurements might contribute to reducing dose. Purpose...... To compare leg length measurements performed on diagnostic images and low dose preview images both acquired using a low-dose bi-planar imaging system. Material and Methods Preview and diagnostic images from 22 patients were retrospectively collected (14 girls, 8 boys; mean age, 12.8 years; age range, 10...... strongly imply that leg length measurements performed on preview images from a low-dose bi-planar imaging system are comparable to measurements performed on diagnostic images....

  13. Why Have the “Cantankerous Old People” Left the Neighborhood? The Representation of Old Age in Serbian Television Commercials – A Repeated Study

    Directory of Open Access Journals (Sweden)

    Ljubica Milosavljević

    2016-02-01

    Full Text Available The paper represents an attempt to examine to what extent the way in which older members of society are represented in Serbian television commercials has changed in comparison to representations which were present in commercials during the three months in 2009 (Milosavljevic 2010a when the first study was conducted. As was the case in the first study, the focus is on dominant societal attitudes toward old people and old age which were utilized in making the television commercials in question. This was accomplished through analyzing both the positive and the negative stereotypes used to convey meaning in the commercials which were analyzed, as well as through the analysis of the proportional representation of older characters in advertising. The commercials which were analyzed here were broadcasted during the second half of December 2012, January and the first half of February 2013.

  14. [Intravenous Sedation and Repeated "the Same Day General Anesthesia" for a School-age Boy with Dandy-Walker Syndrome and Dentinogenesis].

    Science.gov (United States)

    Hitosugi, Takashi; Tsukamoto, Masanori; Fujiwara, Shigeki; Yokoyama, Takeshi

    2016-03-01

    Dandy-Walker syndrome (DWS) is characterized by perfect or partial defect of the cerebellum vermis and cystic dilatation of the posterior fossa communicating with the fourth ventricle. Common clinical signs are mental retardation, cerebellar ataxia, and those of increased intracranial pressure (ICP). Associated congenital anomalies are craniofacial, cardiac, renal, and skeletal abnormalities. We experienced a case of intravenous sedation and six times of "the same day" general anesthesia for a school-aged boy (10-13 years old) with DWS and hypodentinogenesis. The patient underwent an examination and dental treatments. We had to pay attention to airway management tracheal tube selection and control of ICP. In addition, we should prevent tooth injuries through mishaps during tracheal intubations, since all-tooth-hypoplasia with fragile dental crowns was strongly suggested in this case. Detailed postoperative care is also required for general anesthesia afflicted with DWS.

  15. [Length and structure of telomeric DNA in three species of Baikal gastropods (Caenogastropoda: Hydrobioidea: Benedictiidae)].

    Science.gov (United States)

    Koroleva, A G; Evtushenko, E V; Maximova, N V; Vershinin, A V; Sintnikova, T Y; Kirilchik, S V

    2015-03-01

    The structure of telomeric repeat (TTAGGG)n was determined and the length of telomeric DNA (tDNA) was measured in three species of gastropods from the family Benedictiidae that are endemic to Lake Baikal. Fluorescence in situ hybridization (FISH) confirmed the localization of a telomeric repeat at the chromosome ends. The sizes of tDNA in "giant" eurybathic, psammo-pelobiontic species Benedictia fragilis and shallow water litho-psammobiontic species B. baicalensis with medium shell sizes were similar (16 ± 2.9 and 15 ± 2.1 kb, respectively), but they had a greater length than that of the shallow water spongio-litobiontic species Kobeltocochlea martensiana with small shells (10.5 ± 1.5 kb). We discuss tendencies in age-related changes in tDNA length in snails and a possible mechanism for maintaining tDNA size in ontogeny.

  16. Seat adjustment--capacity and repeatability among occupants in a modern car.

    Science.gov (United States)

    Jonsson, Bertil; Stenlund, Hans; Svensson, Mats Y; Björnstig, Ulf

    2008-02-01

    Families in the Western world have a car and several family members share the same car. In this study, 154 participants have adjusted a driver's seat three times. The primary objective was to study intrapersonal repeatability and intraclass correlation (ICC) on seat; length adjustment, backrest angle, seat front edge and seat rear edge adjustment, related to participant age, sex, stature and weight. Length adjustment has the best intrapersonal repeatability within two repetitions, 49 mm and ICC-value 0.87. Females and younger participants (age < 40 years) adjust seats generally more accurately. Females adjust the seat 41 mm more forward, 120 mm compared to men 79 mm counted from 0-starting position. Females sit with more upright seat backrests, 46 degree compared to 43 degrees for males counted from 0-starting position. Females sit higher than males in both the frontal and rear part of the seat cushion.

  17. Age, breed designation, coat color, and coat pattern influenced the length of stay of cats at a no-kill shelter.

    Science.gov (United States)

    Brown, William P; Morgan, Kelsey T

    2015-01-01

    Adoption records from the Tompkins County Society for the Prevention of Cruelty to Animals, an open-admission, no-kill shelter in New York State, were examined to determine if various physical attributes influenced the length of stay (LOS) of cats and kittens. Similar reports from other no-kill shelters have not been published. LOS averaged 61.2 days for cats and kittens combined and ranged from less than 1 day to 730 days. Based on mixed models that accounted for lack of independence among attributes, younger, lighter-colored cats were generally adopted more quickly than older, more darkly colored cats, but yellow-colored cats had the greatest LOS. Coat color did not influence LOS for kittens. Coat patterning and breed designation influenced LOS in both cats and kittens. Male cats and kittens had a shorter LOS than female cats and kittens, respectively. Studies from traditional shelters also demonstrated the importance of physical characteristics to adopters. Given adopter preferences for companion animals with certain characteristics, methods to reduce the LOS for cats with the longest potential residences at the shelter require continued development.

  18. Influence of Starting Age and Length of Learning on English Pronunciation%年龄和学习时间对英语语音的影响

    Institute of Scientific and Technical Information of China (English)

    谢舒婷

    2012-01-01

    It is generally held that children are superior to adults at second language acquisition.And their impressive ability to achieve a more native-like pronunciation of a foreign language than older students is the most common reason given for beginning foreign language learning in elementary schools.Through a pronunciation test of 60 Chinese students aged 13 to 35,the experiment proved that starting age is definitely a significant factor in the accuracy of pronunciation.Students who learn a foreign language before puberty are more likely to achieve a more native-like pronunciation.%人们普遍认为儿童在第二语言学习方面要优于成人,尤其他们在语音方面的特殊能力给人留下深刻印象,这也是从小学开始外语教育的一个普遍依据。实验通过对60个年龄在13-35岁的中国学生所做的语音测试考察年龄和学习时间对英语语音的影响。实验证明年龄是影响语音能力的一个重要因素,在青春期前学习外语的学生更有可能达到标准的语音水平。

  19. 白内障患者手术年龄和眼轴长度与晶状体厚度相关性分析%Correlation of operation age, axial length and lens thickness in cataract

    Institute of Scientific and Technical Information of China (English)

    孙小银; 徐唐

    2013-01-01

    AIM: To study the correlation of operation age, axial length and lens thickness in cataract eyes. METHODS: A total of 319 patients ( 393 eyes ) were divided into non -high myopia cataract group ( 198 patients, 237 eyes) and high myopia cataract group (121 patients, 156 eyes ) according to the axial length.Axial length and lens thickness were measured with A-mode ultrasound biometry. RESULTS:There were statistical difference in operation age (t=3.614, P=0.000), lens thickness (t=-3.081, P=0.002) between the non-high myopia cataract group and high myopia cataract group.The operation age of high myopia cataract group was younger than that of non-high myopia cataract group.The lens thickness in high myopia cataract group was thicker than that in non-high myopia cataract group. There was no significant correlation between age and axial length in the non-high myopia cataract group (r=-0.081, P=0.214).Age and lens thickness had positive correlation in the non-high myopia cataract group (r=0.178, P=0.006).Axial length and lens thickness had no significant correlation in the non-high myopia cataract group (r=-0.050, P=0.442). There was a negative correlation between age and lens thickness in the high myopia cataract group ( r=-0.211, P=0.008).Age and lens thickness had no significant correlation in the high myopia cataract group ( r=0.078, P=0.332).Axial length and lens thickness had positive correlation in the high myopia cataract group ( r=0.207, P=0.010). CONCLUSION: For the non -high myopia cataract patients, the cataract aggravate as the age increase.The operation age will not change as the axial length change. For the high myopia cataract patients, the cataract will not aggravate as the age increase, and the longer of the axial length, the younger of the operation age.%目的:探讨白内障患者手术年龄、眼轴长度、晶状体厚度之间相关性。方法:将319例393眼白内障患者根据眼轴长度分为非高度近视白内障组198例237

  20. High increments of overweight along with low length-for-age growth during the first 24 months of life Aumento de sobrepeso con bajo crecimiento de talla-para-edad durante los primeros 24 meses de vida

    Directory of Open Access Journals (Sweden)

    M. Bacardí-Gascón

    2012-12-01

    Full Text Available Background: It has been reported that children nursed in orphanages loose one month of lineal growth for every three months they spend in the orphanage. Objective: The purpose of this study was to evaluate the daily variation of weight- for- length and length-for-age among infants under 24 months of age, living in a temporary public orphanage in Mexico. Methods: Ninety children from 0 to 24 months of age, who were institutionalized at an orphanage, were assessed during a three month period. Upon arrival their height and weight were measured daily, Monday through Friday. Daily growth velocity for weight and length was calculated. Length-for age (LAZ and weight-for-length (WHZ age z- scores were calculated based on WHO criteria. Risk of overweight (ROW and overweight (OW were classified using the WHO criteria. Results: The increments of daily weight were lower than the normal range (9 g daily, but the ROW and OW increased from 10% and 3% at the beginning of the study to 14% and 11% at the end. At the end of the follow-up, WHZ was inversely associated to length (cm/day velocity (r = -302, p Antecedentes: Se ha descrito que los niños de orfanatorios pierden un mes lineal por cada tres meses que residen en un orfanatorio. Objetivo: El propósito de este estudio fue evaluar la variación diaria de peso-para-talla y talla-para edad, entre infantes de menos de 24 meses de edad, que residen en un orfanatorio público temporal de México Métodos: Se valoraron durante un período de tres meses, noventa niños de 0 a 24 meses de edad, institucionalizados en un orfanatorio. Desde su ingreso se midieron diariamente la estatura y el peso de manera estandarizada, del lunes al viernes. Se calculó la velocidad de crecimiento diario del peso y la estatura. Las puntuaciones del z-score de la talla-para-edad y del peso-para-talla (zPT, se calcularon basados en los criterios de la OMS. El riesgo de sobrepeso (RSP y el sobrepeso (SP se clasificó de acuerdo a los

  1. Estimation of genome length

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The genome length is a fundamental feature of a species. This note outlined the general concept and estimation method of the physical and genetic length. Some formulae for estimating the genetic length were derived in detail. As examples, the genome genetic length of Pinus pinaster Ait. and the genetic length of chromosome Ⅵ of Oryza sativa L. were estimated from partial linkage data.

  2. A Central Limit Theorem for Repeating Patterns

    CERN Document Server

    Abrams, Aaron; Landau, Henry; Landau, Zeph; Pommersheim, James

    2012-01-01

    This note gives a central limit theorem for the length of the longest subsequence of a random permutation which follows some repeating pattern. This includes the case of any fixed pattern of ups and downs which has at least one of each, such as the alternating case considered by Stanley in [2] and Widom in [3]. In every case considered the convergence in the limit of long permutations is to normal with mean and variance linear in the length of the permutations.

  3. Keeping disease at arm's length

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    2015-01-01

    active ageing change everyday life with chronic disease, and how do older people combine an active life with a range of chronic diseases? The participants in the study use activities to keep their diseases at arm’s length, and this distancing of disease at the same time enables them to engage in social...... and physical activities at the activity centre. In this way, keeping disease at arm’s length is analysed as an ambiguous health strategy. The article shows the importance of looking into how active ageing is practised, as active ageing seems to work well in the everyday life of the older people by not giving...... emphasis to disease. The article is based on ethnographic fieldwork and uses vignettes of four participants to show how they each keep diseases at arm’s length....

  4. Predictive Analysis of Age, Service Length and Negative Thinking for Nurses’ Depression%年龄、护龄及负性思维对护士抑郁的预测性研究

    Institute of Scientific and Technical Information of China (English)

    孙笑笑; 张俐; 赖鑫; 陈林娟; 许锐思; 左璇

    2013-01-01

    Objective To explore the relationship among age, service length, negative thinking and nurses’ depression and their predictive value for depression. Methods With simple random sampling, 126 nurses were selected to participate in the investigation with Self-Rating Depression Scale and Automatic Thoughts Questionnaire. Results Positive rate of depression reached 34.1% and there was a positive relationship between depression and negative thinking (r=0.68,P<0.01), a negative relationship among service length, age and depression (r=-0.33, -0.34, P<0.01). Conversely, negative thinking exerted influence on depression directly (B=0.31, P<0.01) and service length influenced negative thinking directly (B=-1.42, P<0.05) while influenced depression indirectly. Meanwhile, there was direct relationship between age and service length (B=1.07, P<0.01),and indirect relationship between age and depression. Conclusion Mean score of depression in the study is higher than that in the norm and there is close relationship among negative thinking, service length, age and depression. The former three factors have predictive values for depression, with negative thinking the top.%  目的探究年龄、护龄及负性思维与护士抑郁情绪的相关关系及对其的预测性.方法采用简单随机抽样法,对在某大学参加培训的126名在岗护士,进行自评抑郁量表及自动思维问卷测评,分析抑郁和负性思维得分水平,以及抑郁与人口学特征、负性思维得分的相关性.结果该组护士抑郁检出率为34.1%.抑郁与负性思维呈正相关(r=0.68,P<0.01),与护龄、年龄呈负相关(r=-0.33,-0.34,P<0.01).负性思维直接影响抑郁(B=0.31,P<0.01).护龄直接影响负性思维(B=-1.42,P<0.05),间接影响抑郁.年龄直接影响护龄(B=1.07,P<0.01),间接影响抑郁.结论该组护士抑郁均分高于常模,负性思维、护龄、年龄与抑郁相关程度比较密切,且对抑郁均有一定的预测性,以负性思维的预测性最为突出.

  5. Childhood experiences and repeated suicidal behavior

    DEFF Research Database (Denmark)

    Krarup, Gertrud; Nielsen, Bent; Rask, P

    1991-01-01

    The aim of this study was to elucidate the influence of various events in childhood on suicidal behavior in adult age. For this purpose, 99 patients admitted to the Department of Psychiatry of Odense University Hospital after making a suicide attempt were followed for 5 years, to register repeated...... suicidal behavior. The results showed that three fourths of the patients attempted suicide more than once (62% nonfatal and 14% fatal outcome). The sex distribution was about the same among the first-evers as among the repeaters. Most repeaters were younger people in their twenties and thirties......, and the first-evers on average were past the age of 40. Somewhat unexpectedly, significantly more repeaters than first-evers had grown up with both their parents. However, the results also showed that significantly more repeaters than first-evers had had an unhappy childhood. This indicates...

  6. Quantum repeated games revisited

    CERN Document Server

    Frackiewicz, Piotr

    2011-01-01

    We present a scheme for playing quantum repeated 2x2 games based on the Marinatto and Weber's approach to quantum games. As a potential application, we study twice repeated Prisoner's Dilemma game. We show that results not available in classical game can be obtained when the game is played in the quantum way. Before we present our idea, we comment on the previous scheme of playing quantum repeated games.

  7. Studies of an expanded trinucleotide repeat in transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Bingham, P.; Wang, S.; Merry, D. [Univ. of Pennsylvania, Philadelphia, PA (United States)

    1994-09-01

    Spinal and bulbar muscular atrophy (SBMA) is a progressive motor neuron disease caused by expansion of a trinucleotide repeat in the androgen receptor gene (AR{sup exp}). AR{sup exp} repeats expand further or contract in approximately 25% of transmissions. Analogous {open_quotes}dynamic mutations{close_quotes} have been reported in other expanded trinucleotide repeat disorders. We have been developing a mouse model of this disease using a transgenic approach. Expression of the SBMA AR was documented in transgenic mice with an inducible promoter. No phenotypic effects of transgene expression were observed. We have extended our previous results on stability of the expanded trinucleotide repeat in transgenic mice in two lines carrying AR{sup exp}. Tail DNA was amplified by PCR using primers spanning the repeat on 60 AR{sup exp} transgenic mice from four different transgenic lines. Migration of the PCR product through an acrylamide gel showed no change of the 45 CAG repeat length in any progeny. Similarly, PCR products from 23 normal repeat transgenics showed no change from the repeat length of the original construct. Unlike the disease allele in humans, the expanded repeat AR cDNA in transgenic mice showed no change in repeat length with transmission. The relative stability of CAG repeats seen in the transgenic mice may indicate either differences in the fidelity of replicative enzymes, or differences in error identification and repair between mice and humans. Integration site or structural properties of the transgene itself might also play a role.

  8. CAG repeat variants in the POLG1 gene encoding mtDNA polymerase-gamma and risk of breast cancer in African-American women.

    Science.gov (United States)

    Azrak, Sami; Ayyasamy, Vanniarajan; Zirpoli, Gary; Ambrosone, Christine; Bandera, Elisa V; Bovbjerg, Dana H; Jandorf, Lina; Ciupak, Gregory; Davis, Warren; Pawlish, Karen S; Liang, Ping; Singh, Keshav

    2012-01-01

    The DNA polymerase-gamma (POLG) gene, which encodes the catalytic subunit of enzyme responsible for directing mitochondrial DNA replication in humans, contains a polyglutamine tract encoded by CAG repeats of varying length. The length of the CAG repeat has been associated with the risk of testicular cancer, and other genomic variants that impact mitochondrial function have been linked to breast cancer risk in African-American (AA) women. We evaluated the potential role of germline POLG-CAG repeat variants in breast cancer risk in a sample of AA women (100 cases and 100 age-matched controls) who participated in the Women's Circle of Health Study, an ongoing multi-institutional, case-control study of breast cancer. Genotyping was done by fragment analysis in a blinded manner. Results from this small study suggest the possibility of an increased risk of breast cancer in women with minor CAG repeat variants of POLG, but no statistically significant differences in CAG repeat length were observed between cases and controls (multivariate-adjusted odds ratio 1.74; 95% CI, 0.49-6.21). Our study suggests that POLG-CAG repeat length is a potential risk factor for breast cancer that needs to be explored in larger population-based studies.

  9. CAG repeat variants in the POLG1 gene encoding mtDNA polymerase-gamma and risk of breast cancer in African-American women.

    Directory of Open Access Journals (Sweden)

    Sami Azrak

    Full Text Available The DNA polymerase-gamma (POLG gene, which encodes the catalytic subunit of enzyme responsible for directing mitochondrial DNA replication in humans, contains a polyglutamine tract encoded by CAG repeats of varying length. The length of the CAG repeat has been associated with the risk of testicular cancer, and other genomic variants that impact mitochondrial function have been linked to breast cancer risk in African-American (AA women. We evaluated the potential role of germline POLG-CAG repeat variants in breast cancer risk in a sample of AA women (100 cases and 100 age-matched controls who participated in the Women's Circle of Health Study, an ongoing multi-institutional, case-control study of breast cancer. Genotyping was done by fragment analysis in a blinded manner. Results from this small study suggest the possibility of an increased risk of breast cancer in women with minor CAG repeat variants of POLG, but no statistically significant differences in CAG repeat length were observed between cases and controls (multivariate-adjusted odds ratio 1.74; 95% CI, 0.49-6.21. Our study suggests that POLG-CAG repeat length is a potential risk factor for breast cancer that needs to be explored in larger population-based studies.

  10. Repeater For A Digital-Communication Bus

    Science.gov (United States)

    Torres-Guzman, Esteban; Olson, Stephen; Heaps, Tim

    1993-01-01

    Digital repeater circuit designed to extend range of communication on MIL-STD-1553 bus beyond original maximum allowable length of 300 ft. Circuit provides two-way communication, one way at time, and conforms to specifications of MIL-STD-1553. Crosstalk and instability eliminated.

  11. A Repeater in the Language Laboratory

    Science.gov (United States)

    Griffiths, B. T.

    1969-01-01

    Discusses the feasilility of the use of repeater devices in the language laboratory in order to enable the student to "recapitulate effortlessly and and indefinitely any utterance of any length which is causing him difficulty or is of special interest. (FWB)

  12. Computel: computation of mean telomere length from whole-genome next-generation sequencing data.

    Science.gov (United States)

    Nersisyan, Lilit; Arakelyan, Arsen

    2015-01-01

    Telomeres are the ends of eukaryotic chromosomes, consisting of consecutive short repeats that protect chromosome ends from degradation. Telomeres shorten with each cell division, leading to replicative cell senescence. Deregulation of telomere length homeostasis is associated with the development of various age-related diseases and cancers. A number of experimental techniques exist for telomere length measurement; however, until recently, the absence of tools for extracting telomere lengths from high-throughput sequencing data has significantly obscured the association of telomere length with molecular processes in normal and diseased conditions. We have developed Computel, a program in R for computing mean telomere length from whole-genome next-generation sequencing data. Computel is open source, and is freely available at https://github.com/lilit-nersisyan/computel. It utilizes a short-read alignment-based approach and integrates various popular tools for sequencing data analysis. We validated it with synthetic and experimental data, and compared its performance with the previously available software. The results have shown that Computel outperforms existing software in accuracy, independence of results from sequencing conditions, stability against inherent sequencing errors, and better ability to distinguish pure telomeric sequences from interstitial telomeric repeats. By providing a highly reliable methodology for determining telomere lengths from whole-genome sequencing data, Computel should help to elucidate the role of telomeres in cellular health and disease.

  13. Computel: computation of mean telomere length from whole-genome next-generation sequencing data.

    Directory of Open Access Journals (Sweden)

    Lilit Nersisyan

    Full Text Available Telomeres are the ends of eukaryotic chromosomes, consisting of consecutive short repeats that protect chromosome ends from degradation. Telomeres shorten with each cell division, leading to replicative cell senescence. Deregulation of telomere length homeostasis is associated with the development of various age-related diseases and cancers. A number of experimental techniques exist for telomere length measurement; however, until recently, the absence of tools for extracting telomere lengths from high-throughput sequencing data has significantly obscured the association of telomere length with molecular processes in normal and diseased conditions. We have developed Computel, a program in R for computing mean telomere length from whole-genome next-generation sequencing data. Computel is open source, and is freely available at https://github.com/lilit-nersisyan/computel. It utilizes a short-read alignment-based approach and integrates various popular tools for sequencing data analysis. We validated it with synthetic and experimental data, and compared its performance with the previously available software. The results have shown that Computel outperforms existing software in accuracy, independence of results from sequencing conditions, stability against inherent sequencing errors, and better ability to distinguish pure telomeric sequences from interstitial telomeric repeats. By providing a highly reliable methodology for determining telomere lengths from whole-genome sequencing data, Computel should help to elucidate the role of telomeres in cellular health and disease.

  14. Preliminary evidence for an association of a dinucleotide repeat polymorphism at the MAOA gene with early onset alcoholism/substance abuse

    Energy Technology Data Exchange (ETDEWEB)

    Vanyukov, M.M.; Moss, H.B.; Tarter, R.E. [Univ. of Pittsburg, PA (United States)] [and others

    1995-04-24

    An association between the liability to early onset alcoholism/substance abuse and a recently discovered dinucleotide repeat length polymorphism at the MAOA gene (MAOCA-1) was examined using polymerase chain reaction (PCR). A significant correlation between the presence/absence of the disorder and the length of the MAOCA-1 repeat was found in males, but not females, with {open_quotes}long{close_quotes} alleles (repeat length above 115 bp) associated with both increased risk for the disorder and lower age of onset of substance abuse. These preliminary data suggest that further exploration of the relationship between the MAOA gene and behavioral traits in an expanded sample is warranted. 22 refs., 1 fig., 3 tabs.

  15. Age at onset variance analysis in spinocerebellar ataxias : a study in a Dutch-French cohort

    NARCIS (Netherlands)

    Warrenburg, B.P.C. van de; Hendriks, H.; Durr, A.; Zuijlen, M.C.A. van; Stevanin, G.; Camuzat, A.; Sinke, R.J.; Brice, A.; Kremer, H.P.H.

    2005-01-01

    In dominant spinocerebellar ataxias (SCAs), the issue of whether non-CAG dependent factors contribute to onset age remains unsettled. Data on SCA genotype, onset age, normal/expanded CAG repeat length, sex of the patient and transmitting parent, and family details were available from 802 patients. B

  16. Exploring Genetic Factors Involved in Huntington Disease Age of Onset

    DEFF Research Database (Denmark)

    Valcárcel-Ocete, Leire; Alkorta-Aranburu, Gorka; Iriondo, Mikel;

    2015-01-01

    Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of ...

  17. Association of second to fourth digit length ratio (2D:4D with some anthropometric measurements: a comparison between Polish and Indian young adults aged 18-25 years

    Directory of Open Access Journals (Sweden)

    R. Chakraborty

    2015-07-01

    Full Text Available Background: The ratio of lengths of second to the fourth digit (2D:4D is a proxy indicator of prenatal sex-hormone exposure. The male has lower 2D:4D than the female. The ratio and its sexual dimorphism vary across ethnicity. The relationships of 2D:4D with anthropometric dimensions are not consistent. Objective: To compare 2D:4D and its sexual dimorphism between the young Indian and Polish populations and to examine the relationship between 2D:4D and anthropometric measures. Methods: This cross-sectional study included 152 Indian (males: 71 females: 81 and 110 Polish (55 each sex young adults aged between 18 and 25 years. Height, weight, waist and hip circumferences, second and fourth digit lengths were measured. Results: Males had significantly lower 2D:4D than the female in both hands in both the ethnic groups. All the anthropometric measurements were higher in Polish males, including the 2D:4D of both hands, than the Indians, except for BMI and WHR. Polish females had higher digit lengths, height, weight and HC than the Indian females. In Polish males, 2D:4D was negatively associated with height and WHR in both hands. No significant correlation was observed between any anthropometric measure (except for height and 2D:4D among the Indians. However, the Indian Female had a nearly significant positive correlation between left 2D:4D and HC. In Indian Male correlation between left hand 2D:4D and Height is significant and similar to that of the Polish men. Conclusion: It was not possible to draw any conclusion regarding the nature of association between 2D:4D and anthropometric parameters. The findings indicate a link between fat patterning and digit ratio.

  18. Problems and solutions for the analysis of somatic CAG repeat expansion and their relationship to Huntington's disease toxicity.

    Science.gov (United States)

    Budworth, Helen; McMurray, Cynthia T

    2016-01-01

    Huntington's Disease is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. Whether somatic expansion contributed to toxicity was unknown. From extensive work from multiple laboratories, it has been made clear that toxicity depended on length of the inherited allele, but whether preventing or delaying somatic repeat expansion in vivo would be beneficial was unknown, since the inherited disease allele was still expressed. In Budworth et al., we provided definitive evidence that suppressing the somatic expansion in mice substantially delays disease onset in littermates that inherit the same disease-length allele. This key discovery opens the door for therapeutic approaches targeted at stopping or shortening the CAG tract during life. The analysis was difficult and, at times, non-standard. Here, we take the opportunity to discuss the challenges, the analytical solutions, and to address some controversial issues with respect to expansion biology.

  19. Androgen insensitivity syndrome: do trinucleotide repeats in androgen receptor gene have any role?

    Institute of Scientific and Technical Information of China (English)

    Singh Rajender; Nalini J. Gupta; Baidyanath Chakravarty; Lalji Singh; Kumarasamy Thangaraj

    2008-01-01

    Aim: To investigate the role of CAG and GGN repeats as genetic background affecting androgen insensitivity syn- drome (AIS) phenotype. Methods: We analyzed lengths of androgen receptor (AR)-CAG and GGN repeats in 69 AIS cases, along with 136 unrelated normal male individuals. The lengths of repeats were analyzed using polymerase chain reaction (PCR) amplification followed by allelic genotyping to determine allele length. Results: Our study revealed significantly shorter mean lengths of CAG repeats in patients (mean 18.25 repeats, range 14-26 repeats) in comparison to the controls (mean 22.57 repeats, range 12-39 repeats) (two-tailed P < 0.0001). GGN repeats, however, did not differ significantly between patients (mean 21.48 repeats) and controls (mean 21.21 repeats) (two- tailed P = 0.474). Among patients' groups, the mean number of CAG repeats in partial androgen insensitivity cases (mean 15.83 repeats) was significantly less than in complete androgen insensitivity cases (mean 19.46 repeats) (two- tailed P < 0.0001). Conclusion: The findings suggest that shorter lengths of repeats in the AR gene might act as low penetrance genetic background in varying manifestation of androgen insensitivity. (Asian J Androl 2008 Jul; 10: 616-624)

  20. Genetic study of gestation length in Andalusian and Arabian mares.

    Science.gov (United States)

    Valera, M; Blesa, F; Dos Santos, R; Molina, A

    2006-09-01

    The length of gestation in Andalusian, or Spanish Purebred (SPB) and Arabian (AB) mares reared in Spain was analysed, based on 766 spontaneous full-term deliveries appertaining to 141 mares of SPB breed and 72 mares of AB breed in 31 breeding seasons. The data were obtained from the Yeguada Militar de Jerez de la Frontera stud farm in Cádiz, Spain. The mean length of gestation was of 336.8+/-0.48 days in the SPB mares and 340.3+/-0.63 days in AB mares. To assess the accurate prediction of time of birth the potential effect of a number of factors was investigated. The influences of the breed, mare, month and year of mating, age of the mother, number of births and sex of the foal were statistically significant. The factor have the greatest influence over the gestation length was the mare itself, with a correlation among consecutive births of around 0.4. The effect of inbreeding, both of the mare and foal, was negligible. Gestation length shortened as the breeding season progressed: in both breeds, a delay of 1 month in mating corresponded to a decrease of 3 days in the gestation length. According to our results, gestation length decrease as the mare gets older, with the shortest gestation periods when the mare is 10-12 years old, and from this point on, it slowly increases. The gestation period shortens as the 4th or 5th birth approaches, and then gets progressively longer. The range of variation in gestation length due to the number of births to the mare is of 2.9 days for the AB mares, and 2.2 days for SPB mares. The heritability for the gestation length for AB and the SPB breeds was 0.2, with a repeatability of 0.36 and 0.37, for SPB and AB breeds, respectively. With the data from both breeds, and using a classical approach, the response to selection was estimated if mares with extreme gestation lengths were culled, i.e. lengths which are under 310 days, or over 360 days. According to our results, in the case of SPB, a decrease of 14-45% would occur in the number

  1. Nonpharmacological Interventions Targeted at Delirium Risk Factors, Delivered by Trained Volunteers (Medical and Psychology Students), Reduced Need for Antipsychotic Medications and the Length of Hospital Stay in Aged Patients Admitted to an Acute Internal Medicine Ward: Pilot Study

    Science.gov (United States)

    Piotrowicz, Karolina; Rewiuk, Krzysztof; Halicka, Monika; Kalwak, Weronika; Rybak, Paulina

    2017-01-01

    Purpose. Effectiveness of nonpharmacological multicomponent prevention delivered by trained volunteers (medical and psychology students), targeted at delirium risk factors in geriatric inpatients, was assessed at an internal medicine ward in Poland. Patients and Methods. Participants were recruited to intervention and control groups at the internal medicine ward (inclusion criteria: age ≥ 75, acute medical condition, basic orientation, and logical contact on admission; exclusion criteria: life expectancy delirium episodes, and antipsychotic prescriptions were assessed retrospectively from medical documentation. Results. 130 patients (38.4% males) participated in the study, with 65 in the intervention group. Antipsychotic medications were initiated less frequently in the intervention group compared to the control group. There was a trend towards a shorter hospitalization time and a not statistically significant decrease in deaths in the intervention group. Conclusion. Nonpharmacological multicomponent intervention targeted at delirium risk factors effectively reduced length of hospitalization and need for initiating antipsychotic treatment in elderly patients at the internal medicine ward. PMID:28164113

  2. Polymerase chain reaction and Southern blot-based analysis of the C9orf72 hexanucleotide repeat in different motor neuron diseases.

    Science.gov (United States)

    Hübers, Annemarie; Marroquin, Nicolai; Schmoll, Birgit; Vielhaber, Stefan; Just, Marlies; Mayer, Benjamin; Högel, Josef; Dorst, Johannes; Mertens, Thomas; Just, Walter; Aulitzky, Anna; Wais, Verena; Ludolph, Albert C; Kubisch, Christian; Weishaupt, Jochen H; Volk, Alexander E

    2014-05-01

    The GGGGCC-hexanucleotide repeat expansion in C9orf72 is the most common genetic cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. This study determined the frequency of C9orf72 repeat expansions in different motor neuron diseases (amyotrophic lateral sclerosis (ALS), motor neuron diseases affecting primarily the first or the second motor neuron and hereditary spastic paraplegia). Whereas most studies on C9orf72 repeat expansions published so far rely on a polymerase chain reaction-based screening, we applied both polymerase chain reaction-based techniques and Southern blotting. Furthermore, we determined the sensitivity and specificity of Southern blotting of the C9orf72 hexanucleotide repeat in DNA derived from lymphoblastoid cell lines. C9orf72 repeat expansions were found in 27.1% out of 166 familial ALS patients, only once in 68 sporadic ALS patients, and not in 61 hereditary spastic paraplegia patients or 52 patients with motor neuron diseases affecting clinically primarily either the first or the second motor neuron. We found hints for a correlation between C9orf72 repeat length and the age of onset. Somatic instability of the C9orf72 repeat was observed in lymphoblastoid cell lines compared with DNA derived from whole blood from the same patient and therefore caution is warranted for repeat length determination in immortalized cell lines.

  3. Alu repeats as markers for forensic DNA analyses

    Energy Technology Data Exchange (ETDEWEB)

    Batzer, M.A.; Alegria-Hartman, M. [Lawrence Livermore National Lab., CA (United States); Kass, D.H. [Louisiana State Univ., New Orleans, LA (United States)] [and others

    1994-01-01

    The Human-Specific (HS) subfamily of Alu sequences is comprised of a group of 500 nearly identical members which are almost exclusively restricted to the human genome. Individual subfamily members share an average of 98.9% nucleotide identity with the HS subfamily consensus sequence, and have an average age of 2.8 million years. We have developed a Polymerase Chain Reaction (PCR) based assay using primers complementary to the 5 inch and 3 inch unique flanking DNA sequences from each HS Alu that allow the locus to be assayed for the presence or absence of the Alu repeat. The dimorphic HS Alu sequences probably inserted in the human genome after the radiation of modem humans (within the last 200,000-one million years) and represent a unique source of information for human population genetics and forensic DNA analyses. These sites can be developed into Dimorphic Alu Sequence Tagged Sites (DASTS) for the Human Genome Project. HS Alu family member insertions differ from other types of polymorphism (e.g. Variable Number of Tandem Repeat [VNTR] or Restriction Fragment Length Polymorphism [RFLP]) in that polymorphisms due to Alu insertions arise as a result of a unique event which has occurred only one time in the human population and spread through the population from that point. Therefore, individuals that share HS Alu repeats inherited these elements from a common ancestor. Most VNTR and RFLP polymorphisms may arise multiple times in parallel within a population.

  4. Emotions and family interactions in childhood: Associations with leukocyte telomere length emotions, family interactions, and telomere length.

    Science.gov (United States)

    Robles, Theodore F; Carroll, Judith E; Bai, Sunhye; Reynolds, Bridget M; Esquivel, Stephanie; Repetti, Rena L

    2016-01-01

    Conceptualizations of links between stress and cellular aging in childhood suggest that accumulating stress predicts shorter leukocyte telomere length (LTL). At the same time, several models suggest that emotional reactivity to stressors may play a key role in predicting cellular aging. Using intensive repeated measures, we tested whether exposure or emotional "reactivity" to conflict and warmth in the family were related to LTL. Children (N=39; 30 target children and 9 siblings) between 8 and 13 years of age completed daily diary questionnaires for 56 consecutive days assessing daily warmth and conflict in the marital and the parent-child dyad, and daily positive and negative mood. To assess exposure to conflict and warmth, diary scale scores were averaged over the 56 days. Mood "reactivity" was operationalized by using multilevel modeling to generate estimates of the slope of warmth or conflict scores (marital and parent-child, separately) predicting same-day mood for each individual child. After diary collection, a blood sample was collected to determine LTL. Among children aged 8-13 years, a stronger association between negative mood and marital conflict, suggesting greater negative mood reactivity to marital conflict, was related to shorter LTL (B=-1.51, ptelomere length.

  5. Reconfigurable multiport EPON repeater

    Science.gov (United States)

    Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

    2009-11-01

    An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

  6. Revisiting the TALE repeat.

    Science.gov (United States)

    Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

    2014-04-01

    Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

  7. Survey of simple sequence repeats in woodland strawberry (Fragaria vesca).

    Science.gov (United States)

    Guan, L; Huang, J F; Feng, G Q; Wang, X W; Wang, Y; Chen, B Y; Qiao, Y S

    2013-07-30

    The use of simple sequence repeats (SSRs), or microsatellites, as genetic markers has become popular due to their abundance and variation in length among individuals. In this study, we investigated linkage groups (LGs) in the woodland strawberry (Fragaria vesca) and demonstrated variation in the abundances, densities, and relative densities of mononucleotide, dinucleotide, and trinucleotide repeats. Mononucleotide, dinucleotide, and trinucleotide repeats were more common than longer repeats in all LGs examined. Perfect SSRs were the predominant SSR type found and their abundance was extremely stable among LGs and chloroplasts. Abundances of mononucleotide, dinucleotide, and trinucleotide repeats were positively correlated with LG size, whereas those of tetranucleotide and hexanucleotide SSRs were not. Generally, in each LG, the abundance, relative abundance, relative density, and the proportion of each unique SSR all declined rapidly as the repeated unit increased. Furthermore, the lengths and frequencies of SSRs varied among different LGs.

  8. Novel BAC mouse model of Huntington’s disease with 225 CAG repeats exhibits an early widespread and stable degenerative phenotype

    Science.gov (United States)

    Wegrzynowicz, Michal; Bichell, Terry Jo; Soares, Barbara D.; Loth, Meredith K.; McGlothan, Jennifer L.; Alikhan, Fatima S.; Hua, Kegang; Coughlin, Jennifer M.; Holt, Hunter K.; Jetter, Christopher S.; Mori, Susumu; Pomper, Martin G.; Osmand, Alexander P.; Guilarte, Tomás R.; Bowman, Aaron B.

    2015-01-01

    BACKGROUND Unusually large CAG repeat expansions (>60) in exon one of Huntingtin (HTT) are invariably associated with a juvenile-onset form of Huntington’s disease (HD), characterized by a more extensive and rapidly progressing neuropathology than the more prevalent adult-onset form. However, existing mouse models of HD that express the full-length Htt gene with CAG repeat lengths associated with juvenile HD (ranging between ~75 to ~150 repeats in published models) exhibit selective neurodegenerative phenotypes more consistent with adult-onset HD. OBJECTIVE To determine if a very large CAG repeat (>200) in full-length Htt elicits neurodegenerative phenotypes consistent with juvenile HD. METHODS Using a bacterial artificial chromosome (BAC) system, we generated mice expressing full-length mouse Htt with ~225 CAG repeats under control of the mouse Htt promoter. Mice were characterized using behavioral, neuropathological, biochemical and brain imaging methods. RESULTS BAC-225Q mice exhibit phenotypes consistent with a subset of features seen in juvenile-onset HD: very early motor behavior abnormalities, reduced body weight, widespread and progressive increase in Htt aggregates, gliosis, and neurodegeneration. Early striatal pathology was observed, including reactive gliosis and loss of dopamine receptors, prior to detectable volume loss. HD-related blood markers of impaired energy metabolism and systemic inflammation were also increased. Aside from an age-dependent progression of diffuse nuclear aggregates at 6 months of age to abundant neuropil aggregates at 12 months of age, other pathological and motor phenotypes showed little to no progression. CONCLUSIONS The HD phenotypes present in animals 3 to 12 months of age make the BAC-225Q mice a unique and stable model of full-length mutant Htt associated phenotypes, including body weight loss, behavioral impairment and HD-like neurodegenerative phenotypes characteristic of juvenile-onset HD and/or late-stage adult

  9. Nonpharmacological Interventions Targeted at Delirium Risk Factors, Delivered by Trained Volunteers (Medical and Psychology Students, Reduced Need for Antipsychotic Medications and the Length of Hospital Stay in Aged Patients Admitted to an Acute Internal Medicine Ward: Pilot Study

    Directory of Open Access Journals (Sweden)

    Stanislaw Gorski

    2017-01-01

    Full Text Available Purpose. Effectiveness of nonpharmacological multicomponent prevention delivered by trained volunteers (medical and psychology students, targeted at delirium risk factors in geriatric inpatients, was assessed at an internal medicine ward in Poland. Patients and Methods. Participants were recruited to intervention and control groups at the internal medicine ward (inclusion criteria: age ≥ 75, acute medical condition, basic orientation, and logical contact on admission; exclusion criteria: life expectancy < 24 hours, surgical hospitalization, isolation due to infectious disease, and discharge to other medical wards. Every day trained volunteers delivered a multicomponent standardized intervention targeted at risk factors of in-hospital complications to the intervention group. The control group, selected using a retrospective individual matching strategy (1 : 1 ratio, regarding age, gender, and time of hospitalization, received standard care. Outcome Measures. Hospitalization time, deaths, falls, delirium episodes, and antipsychotic prescriptions were assessed retrospectively from medical documentation. Results. 130 patients (38.4% males participated in the study, with 65 in the intervention group. Antipsychotic medications were initiated less frequently in the intervention group compared to the control group. There was a trend towards a shorter hospitalization time and a not statistically significant decrease in deaths in the intervention group. Conclusion. Nonpharmacological multicomponent intervention targeted at delirium risk factors effectively reduced length of hospitalization and need for initiating antipsychotic treatment in elderly patients at the internal medicine ward.

  10. Recursive quantum repeater networks

    CERN Document Server

    Van Meter, Rodney; Horsman, Clare

    2011-01-01

    Internet-scale quantum repeater networks will be heterogeneous in physical technology, repeater functionality, and management. The classical control necessary to use the network will therefore face similar issues as Internet data transmission. Many scalability and management problems that arose during the development of the Internet might have been solved in a more uniform fashion, improving flexibility and reducing redundant engineering effort. Quantum repeater network development is currently at the stage where we risk similar duplication when separate systems are combined. We propose a unifying framework that can be used with all existing repeater designs. We introduce the notion of a Quantum Recursive Network Architecture, developed from the emerging classical concept of 'recursive networks', extending recursive mechanisms from a focus on data forwarding to a more general distributed computing request framework. Recursion abstracts independent transit networks as single relay nodes, unifies software layer...

  11. Assembly of Repeat Content Using Next Generation Sequencing Data

    Energy Technology Data Exchange (ETDEWEB)

    labutti, Kurt; Kuo, Alan; Grigoriev, Igor; Copeland, Alex

    2014-03-17

    Repetitive organisms pose a challenge for short read assembly, and typically only unique regions and repeat regions shorter than the read length, can be accurately assembled. Recently, we have been investigating the use of Pacific Biosciences reads for de novo fungal assembly. We will present an assessment of the quality and degree of repeat reconstruction possible in a fungal genome using long read technology. We will also compare differences in assembly of repeat content using short read and long read technology.

  12. Measuring Thermodynamic Length

    Energy Technology Data Exchange (ETDEWEB)

    Crooks, Gavin E

    2007-09-07

    Thermodynamic length is a metric distance between equilibrium thermodynamic states. Among other interesting properties, this metric asymptotically bounds the dissipation induced by a finite time transformation of a thermodynamic system. It is also connected to the Jensen-Shannon divergence, Fisher information, and Rao's entropy differential metric. Therefore, thermodynamic length is of central interestin understanding matter out of equilibrium. In this Letter, we will consider how to denethermodynamic length for a small system described by equilibrium statistical mechanics and how to measure thermodynamic length within a computer simulation. Surprisingly, Bennett's classic acceptance ratio method for measuring free energy differences also measures thermodynamic length.

  13. CAG repeat polymorphism in androgen receptor gene is not directly associated with polycystic ovary syndrome but influences serum testosterone levels.

    Science.gov (United States)

    Skrgatic, L; Baldani, D Pavicic; Cerne, J Z; Ferk, P; Gersak, K

    2012-02-01

    Hyperandrogenemia has been the most consistent feature of polycystic ovary syndrome (PCOS). Androgens exert their effects through androgen receptors (ARs). The expansion of the codon CAG trinucleotide repeat polymorphism in exon 1 of the AR gene represents a type of genetic alteration associated with changes in the AR gene function. The purpose of this study was to establish a possible association of the AR gene CAG repeat length polymorphism with PCOS, and its influence on clinical and biochemical androgen traits. Two hundred and fourteen Croatian women with PCOS and 209 healthy control women of reproductive age were enrolled. Phenotypic hyperandrogenism, BMI and waist to hip ratio were recorded. Hormonal profiles, fasting insulin and glucose levels were measured on cycle days 3-5. Genotyping of the CAG repeat polymorphism in the AR gene was performed. We found no significant difference in the mean CAG repeat number between the PCOS patients and controls (22.1±3.4 vs. 21.9±3.2, P=0.286). There was a positive correlation between the CAG repeat length and total testosterone (TT) in the PCOS group (R=0.225, P=0.015). A multiple linear regression model using mean CAG repeat length, BMI, age and HOMA-IR as predictors explained 8.5% (adjusted R²) of the variability in serum TT levels. In this model the CAG repeat polymorphism was found to be a significant predictor of serum TT levels in PCOS patients (P=0.015). The logistic regression analysis revealed that the CAG repeat length is not a significant predictor of hirsutism and acne status (P=0.921 and P=0.437, respectively). The model was adjusted for serum TT, free testosterone, androstendione and DHEAS levels as independent variables, which were also not found to be significant predictors of hirsutism (P=0.687, P=0.194, P=0.675 and P=0.938, respectively) or acne status (P=0.594, P=0.095, P=0.290 and P=0.151, respectively). In conclusion, the AR CAG repeat polymorphism is not a major determinant of PCOS in the

  14. The Pentapeptide Repeat Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Vetting,M.; Hegde, S.; Fajardo, J.; Fiser, A.; Roderick, S.; Takiff, H.; Blanchard, J.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S, T,A, V][D, N][L, F]-[S, T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Mycobacterium tuberculosis. The structure revealed that the pentapeptide repeats encode the folding of a novel right-handed quadrilateral {beta}-helix. MfpA binds to DNA gyrase and inhibits its activity. The rod-shaped, dimeric protein exhibits remarkable size, shape and electrostatic similarity to DNA.

  15. The heritability of leucocyte telomere length dynamics

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob B; Dalgård, Christine; Möller, Sören;

    2015-01-01

    BACKGROUND: Leucocyte telomere length (LTL) is a complex trait associated with ageing and longevity. LTL dynamics are defined by LTL and its age-dependent attrition. Strong, but indirect evidence suggests that LTL at birth and its attrition during childhood largely explains interindividual LTL...... childhood are crucial for understanding the role of telomere genetics in human ageing and longevity....

  16. Twin correlations of telomere length metrics

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob B; Dalgård, Christine; Möller, Sören;

    2015-01-01

    BACKGROUND: Leucocyte telomere length (LTL) is a complex trait associated with ageing and longevity. LTL dynamics are defined by LTL and its age-dependent attrition. Strong, but indirect evidence suggests that LTL at birth and its attrition during childhood largely explains interindividual LTL...... childhood are crucial for understanding the role of telomere genetics in human ageing and longevity....

  17. Axial Globe Length in Congenital Ptosis.

    Science.gov (United States)

    Takahashi, Yasuhiro; Kang, Hyera; Kakizaki, Hirohiko

    2015-01-01

    To compare axial globe length between affected and unaffected sides in patients with unilateral congenital ptosis. This prospective observational study included 37 patients (age range: 7 months to 58 years). The axial globe length, margin reflex distance-1 (MRD-1), and refractive power were measured. The axial globe length difference was calculated by subtracting the axial globe length on the unaffected side from that of the affected side. The relationships among axial globe length differences, MRD-1 on the affected sides, and patient ages were analyzed using multiple regression analysis. No significant differences were found in the axial globe length between sides (P = .677). The axial globe length difference was 0.17 ± 0.30 mm (mean ± standard deviation), and two patients (5.4%), aged 32 to 57 years, showed axial globe length more than 0.67 mm longer (corresponding to a refractive power of 2 diopters) on the affected side compared to the unaffected side. The multiple regression model between axial globe length difference, patient age, and MRD-1 on the affected sides was less appropriate (YAGL = 0.003XAGE-0.048XMRD-1 +0.112; r = 0.338; adjusted r2 = 0.062; P = .127). The cylindrical power was greater on the affected side (P = .046), although the spherical power was not different between sides (P = .657). No significant difference was identified in the axial globe length between sides, and only 5% of non-pediatric patients showed an axial globe length more than 0.67 mm longer on the affected side. Congenital ptosis may have little effect on axial globe length elongation, and the risk of axial myopia-induced anisometropic amblyopia may be low in patients with unilateral congenital ptosis. Copyright 2015, SLACK Incorporated.

  18. Repeating the Past

    Science.gov (United States)

    Moore, John W.

    1998-05-01

    As part of the celebration of the Journal 's 75th year, we are scanning each Journal issue from 25, 50, and 74 years ago. Many of the ideas and practices described are so similar to present-day "innovations" that George Santayana's adage (1) "Those who cannot remember the past are condemned to repeat it" comes to mind. But perhaps "condemned" is too strong - sometimes it may be valuable to repeat something that was done long ago. One example comes from the earliest days of the Division of Chemical Education and of the Journal.

  19. "Which mouse kissed the frog?" Effects of age of onset, length of exposure, and knowledge of case marking on the comprehension of wh-questions in German-speaking simultaneous and early sequential bilingual children.

    Science.gov (United States)

    Roesch, Anne Dorothee; Chondrogianni, Vasiliki

    2016-05-01

    Studies examining age of onset (AoO) effects in childhood bilingualism have provided mixed results as to whether early sequential bilingual children (eL2) differ from simultaneous bilingual children (2L1) and L2 children on the acquisition of morphosyntax. Differences between the three groups have been attributed to other factors such as length of exposure (LoE), language abilities, and the phenomenon to be acquired. The present study investigates whether four- to five-year-old German-speaking eL2 children differ from 2L1 children on the acquisition of wh-questions, and whether these differences can be explained by AoO, LoE, and/or knowledge of case marking. The 2L1 children outperformed the eL2 children in terms of accuracy; however, both bilingual groups exhibited similar error patterns. This suggests that 2L1 and eL2 bilingual children are sensitive to the same morphosyntactic cues, when comprehending wh-questions. Finally, children's performance on the different types of wh-questions was explained by a combination of knowledge of case marking, LoE, and AoO.

  20. Effects of 3-repeat tau on taxol mobility through microtubules

    Science.gov (United States)

    Park, Hyunjoo; Fygenson, Deborah; Kim, Mahn Won

    2005-03-01

    Both the anti-cancer drug taxol and the microtubule-associated protein tau suppress dynamics of microtubules (MT). We have observed taxol mobility with full-length 3-repeat tau, one of six tau isoforms, using fluorescence recovery after photobleaching (FRAP) on MTs and compare with earlier results on recombinant full-length adult 4-repeat tau. Taxol mobility becomes highly sensitive to taxol concentration in the presence of 3-repeat tau (up to 1:1 molar ratio) as it does in the presence of 4-repeat tau, but is 2 to 3 times faster at low taxol concentrations. Fitting to a mean-field binding reaction model [J.L. Ross et.al, PNAS 101:12910-5 (2004)] suggests that the presence of 3-repeat tau enhances taxol movement through pores in the MT walls.

  1. Inheritance of telomere length in a bird.

    Directory of Open Access Journals (Sweden)

    Thorsten Horn

    Full Text Available Telomere dynamics are intensively studied in human ageing research and epidemiology, with many correlations reported between telomere length and age-related diseases, cancer and death. While telomere length is influenced by environmental factors there is also good evidence for a strong heritable component. In human, the mode of telomere length inheritance appears to be paternal and telomere length differs between sexes, with females having longer telomeres than males. Genetic factors, e.g. sex chromosomal inactivation, and non-genetic factors, e.g. antioxidant properties of oestrogen, have been suggested as possible explanations for these sex-specific telomere inheritance and telomere length differences. To test the influence of sex chromosomes on telomere length, we investigated inheritance and sex-specificity of telomere length in a bird species, the kakapo (Strigops habroptilus, in which females are the heterogametic sex (ZW and males are the homogametic (ZZ sex. We found that, contrary to findings in humans, telomere length was maternally inherited and also longer in males. These results argue against an effect of sex hormones on telomere length and suggest that factors associated with heterogamy may play a role in telomere inheritance and sex-specific differences in telomere length.

  2. 不同年龄、工龄护士职业紧张状况的流行病学调查研究%Epidemiological study of occupational stress prevalence in nurses of different ages and length of service

    Institute of Scientific and Technical Information of China (English)

    余结根; 李荣; 陆琳琳; 匡霞; 贺连平; 康耀文; 陈燕; 金岳龙; 姚应水

    2012-01-01

    Objective:To investigate the occupational stress prevalence in nurses of different ages and length of service for the evidence to provide effective countermeasures. Methods: By convenient cluster sampling, a questionnaire survey, including general demographic information and occupational stress interns, was conducted in 1 144 nurses from seven hospitals in Anhui and Jiangsu Province as well as Shanghai city. Results: Nurses aged between 30 and 40 years scored higher on the items of work responsibilities, heavy work load and assignment impact,the total means of the individual stress and the sub-items except for reaction to interpersonal tension as compared with other groups, whereas the scores were lower re-garding the availability of personal coping resources and refreshment through recreation and leisure activities, which suggested significant statistical difference (P<0.01). As for length of service, those with 5 to 15 years of working experience scored higher on the items of work responsibilities and the sub-items as well as individual stress response, professional work stress response and psychological stress reaction except for the un-clearly stated assignments and sense of responsibility compared with other groups,but scored lower on availability of personal coping resources, a-musement or leisure activities. The difference was statistically significant (P<0.01 or P<0.05). Conclusion: The results of the study suggest that young and middle-aged nurses are undergoing higher burden of occupational stress. Therefore, effective preventive measures should be taken to reduce the impact of occupational stress on the physical and mental health of those subjects to improve their quality of life.%目的:探讨不同年龄和工龄护士的职业紧张水平,为采取有效的干预措施提供依据.方法:采用方便整群抽样方法对安徽省、江苏省和上海市7家医院1 144名护士进行问卷调查,内容包括一般人口

  3. All-optical repeater.

    Science.gov (United States)

    Silberberg, Y

    1986-06-01

    An all-optical device containing saturable gain, saturable loss, and unsaturable loss is shown to transform weak, distorted optical pulses into uniform standard-shape pulses. The proposed device performs thresholding, amplification, and pulse shaping as required from an optical repeater. It is shown that such a device could be realized by existing semiconductor technology.

  4. Bidirectional Manchester repeater

    Science.gov (United States)

    Ferguson, J.

    1980-01-01

    Bidirectional Manchester repeater is inserted at periodic intervals along single bidirectional twisted pair transmission line to detect, amplify, and transmit bidirectional Manchester 11 code signals. Requiring only 18 TTL 7400 series IC's, some line receivers and drivers, and handful of passive components, circuit is simple and relatively inexpensive to build.

  5. Kidney Length in Normal Korean Children

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In One; Cheon, Jung Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of); Lee, Young Seok [Dankook University College of Medicine, Cheonan (Korea, Republic of); Lee, Sun Wha [Ewha Womans University College of Medicine, Seoul (Korea, Republic of); Kim, Ok Hwa [Ajou University College of Medicine, Suwon (Korea, Republic of); Kim, Ji Hye [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Hong Dae [Kangnam Sacred Heart Hospital, Hanllym University College of Medicine, Seoul (Korea, Republic of); Sim, Jung Suk [Mothers Clinic, Bundang, Seongnam (Korea, Republic of)

    2010-09-15

    Renal length offers important information to detect or follow-up various renal diseases. The purpose of this study was to determine the kidney length of normal Korean children in relation to age, height, weight, body surface area (BSA), and body mass index (BMI). Children between 1 month and 15 years of age without urological abnormality were recruited. Children below 3rd percentile and over 97th percentile for height or weight were excluded. Both renal lengths were measured in the prone position three times and then averaged by experienced radiologists. The mean length and standard deviation for each age group was obtained, and regression equation was calculated between renal length and age, weight, height, BSA, and BMI, respectively. Renal length was measured in 550 children. Renal length grows rapidly until 24 month, while the growth rate is reduced thereafter. The regression equation for age is: renal length (mm) = 45.953 + 1.064 x age (month, {<=} 24 months) (R2 = 0.720) or 62.173 + 0.203 x age (months, > 24 months) (R2 = 0.711). The regression equation for height is: renal length (mm) = 24.494 + 0.457 x height (cm) (R2 = 0.894). The regression equation for weight is: renal length (mm) = 38.342 + 2.117 x weight (kg, {<=}18 kg) (R2 = 0.852) or 64.498 + 0.646 x weight (kg, > 18 kg) (R2 = 0.651). The regression equation for BSA is: renal length (mm) = 31.622 + 61.363 x BSA (m2, {<=} 0.7) (R2 = 0.857) or 52.717 + 29.959 x BSA (m2, > 0.7) (R2 = 0.715). The regression equation for BMI is: renal length (mm) = 44.474 + 1.163 x BMI (R2 = 0.079). This study provides data on the normal renal length and its association with age, weight, height, BSA and BMI. The results of this study will guide the detection and follow-up of renal diseases in Korean children

  6. Explaining the length threshold of polyglutamine aggregation

    Science.gov (United States)

    De Los Rios, Paolo; Hafner, Marc; Pastore, Annalisa

    2012-06-01

    The existence of a length threshold, of about 35 residues, above which polyglutamine repeats can give rise to aggregation and to pathologies, is one of the hallmarks of polyglutamine neurodegenerative diseases such as Huntington’s disease. The reason why such a minimal length exists at all has remained one of the main open issues in research on the molecular origins of such classes of diseases. Following the seminal proposals of Perutz, most research has focused on the hunt for a special structure, attainable only above the minimal length, able to trigger aggregation. Such a structure has remained elusive and there is growing evidence that it might not exist at all. Here we review some basic polymer and statistical physics facts and show that the existence of a threshold is compatible with the modulation that the repeat length imposes on the association and dissociation rates of polyglutamine polypeptides to and from oligomers. In particular, their dramatically different functional dependence on the length rationalizes the very presence of a threshold and hints at the cellular processes that might be at play, in vivo, to prevent aggregation and the consequent onset of the disease.

  7. Mononucleotide repeats are asymmetrically distributed in fungal genes

    Directory of Open Access Journals (Sweden)

    de Graaff Leo H

    2008-12-01

    Full Text Available Abstract Background Systematic analyses of sequence features have resulted in a better characterisation of the organisation of the genome. A previous study in prokaryotes on the distribution of sequence repeats, which are notoriously variable and can disrupt the reading frame in genes, showed that these motifs are skewed towards gene termini, specifically the 5' end of genes. For eukaryotes no such intragenic analysis has been performed, though this could indicate the pervasiveness of this distribution bias, thereby helping to expose the selective pressures causing it. Results In fungal gene repertoires we find a similar 5' bias of intragenic mononucleotide repeats, most notably for Candida spp., whereas e.g. Coccidioides spp. display no such bias. With increasing repeat length, ever larger discrepancies are observed in genome repertoire fractions containing such repeats, with up to an 80-fold difference in gene fractions at repeat lengths of 10 bp and longer. This species-specific difference in gene fractions containing large repeats could be attributed to variations in intragenic repeat tolerance. Furthermore, long transcripts experience an even more prominent bias towards the gene termini, with possibly a more adaptive role for repeat-containing short transcripts. Conclusion Mononucleotide repeats are intragenically biased in numerous fungal genomes, similar to earlier studies on prokaryotes, indicative of a similar selective pressure in gene organization.

  8. Small-quantity, lipid-based nutrient supplements provided to women during pregnancy and 6 mo postpartum and to their infants from 6 mo of age increase the mean attained length of 18-mo-old children in semi-urban Ghana: a randomized controlled trial12

    Science.gov (United States)

    Arimond, Mary; Vosti, Stephen; Dewey, Kathryn G

    2016-01-01

    Background: Childhood stunting usually begins in utero and continues after birth; therefore, its reduction must involve actions across different stages of early life. Objective: We evaluated the efficacy of small-quantity, lipid-based nutrient supplements (SQ-LNSs) provided during pregnancy, lactation, and infancy on attained size by 18 mo of age. Design: In this partially double-blind, individually randomized trial, 1320 women at ≤20 wk of gestation received standard iron and folic acid (IFA group), multiple micronutrients (MMN group), or SQ-LNS (LNS group) daily until delivery, and then placebo, MMNs, or SQ-LNS, respectively, for 6 mo postpartum; infants in the LNS group received SQ-LNS formulated for infants from 6 to 18 mo of age (endline). The primary outcome was child length by 18 mo of age. Results: At endline, data were available for 85% of 1228 infants enrolled; overall mean length and length-for-age z score (LAZ) were 79.3 cm and −0.83, respectively, and 12% of the children were stunted (LAZ supplement provided at enrollment, stunting prevalences were 8.9% compared with 15.1% and 11.5%, respectively (P = 0.045). Conclusion: Provision of SQ-LNSs to women from pregnancy to 6 mo postpartum and to their infants from 6 to 18 mo of age may increase the child’s attained length by age 18 mo in similar settings. This trial was registered at clinicaltrials.gov as NCT00970866. PMID:27534634

  9. Leukocyte telomere length in major depression: correlations with chronicity, inflammation and oxidative stress--preliminary findings.

    Directory of Open Access Journals (Sweden)

    Owen M Wolkowitz

    Full Text Available BACKGROUND: Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of "accelerated aging" in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD, whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation. METHODOLOGY: Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio and inflammation (IL-6. Analyses were controlled for age and sex. PRINCIPAL FINDINGS: The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05. Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration was 281 base pairs shorter than that in controls (p<0.05, corresponding to approximately seven years of "accelerated cell aging." Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01 and in the controls (p<0.05 and with inflammation in the depressed subjects (p<0.05. CONCLUSIONS: These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression

  10. Frailty and telomere length: cross-sectional analysis in 3537 older adults from the ESTHER cohort.

    Science.gov (United States)

    Saum, Kai-Uwe; Dieffenbach, Aida Karina; Müezzinler, Aysel; Müller, Heiko; Holleczek, Bernd; Stegmaier, Christa; Butterbach, Katja; Schick, Matthias; Canzian, Federico; Stammer, Hermann; Boukamp, Petra; Hauer, Klaus; Brenner, Hermann

    2014-10-01

    Both telomere length and frailty were observed to be associated with aging. Whether and to what extent telomere length is related to frailty is essentially unknown. In this cross-sectional analysis of baseline data of 3537 community-dwelling adults aged 50 to 75 years of a large German cohort study, we assessed the hypothesis that shorter telomere length might be a biological marker for frailty. Using whole blood DNA we examined mean telomere repeat copy to single gene copy number (T/S ratio) using quantitative PCR. Construction of a frailty index (FI) was based on a deficit accumulation approach, which quantifies frailty as ratio of the deficits present divided by the total number of deficits considered. Mean FI was determined according to age by tertiles of T/S ratio. Furthermore, we used correlation analyses stratified for gender and age groups to examine the association of the T/S ratio with frailty. Mean FI value was similar across tertiles of the T/S ratio (0.24±0.14, 0.24±0.14 and 0.23±0.14, respectively (p=0.09)), and FI and the T/S ratio were uncorrelated in gender- and age-specific analyses. In conclusion, T/S ratio and frailty were unrelated in this large sample of older adults. T/S ratio may therefore not be a meaningful biological marker for frailty.

  11. Minimum Length - Maximum Velocity

    CERN Document Server

    Panes, Boris

    2011-01-01

    We study a framework where the hypothesis of a minimum length in space-time is complemented with the notion of reference frame invariance. It turns out natural to interpret the action of the obtained reference frame transformations in the context of doubly special relativity. As a consequence of this formalism we find interesting connections between the minimum length properties and the modified velocity-energy relation for ultra-relativistic particles. For example we can predict the ratio between the minimum lengths in space and time using the results from OPERA about superluminal neutrinos.

  12. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-01-01

    Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

  13. Repeat surgery after failed midurethral slings

    DEFF Research Database (Denmark)

    Foss Hansen, Margrethe; Lose, Gunnar; Kesmodel, Ulrik Schiøler

    2016-01-01

    MUS from 1998 through 2007. The outcome was repeat surgery with any subsequent procedure code for urinary incontinence within a 5-year period of the first procedure. RESULTS: A total of 5,820 women (mean age 55.4 years, ± 12.1) were registered with a synthetic MUS, and 354 (6 %) underwent reoperation...

  14. Myofilament length dependent activation

    Energy Technology Data Exchange (ETDEWEB)

    de Tombe, Pieter P.; Mateja, Ryan D.; Tachampa, Kittipong; Mou, Younss Ait; Farman, Gerrie P.; Irving, Thomas C. (IIT); (Loyola)

    2010-05-25

    The Frank-Starling law of the heart describes the interrelationship between end-diastolic volume and cardiac ejection volume, a regulatory system that operates on a beat-to-beat basis. The main cellular mechanism that underlies this phenomenon is an increase in the responsiveness of cardiac myofilaments to activating Ca{sup 2+} ions at a longer sarcomere length, commonly referred to as myofilament length-dependent activation. This review focuses on what molecular mechanisms may underlie myofilament length dependency. Specifically, the roles of inter-filament spacing, thick and thin filament based regulation, as well as sarcomeric regulatory proteins are discussed. Although the 'Frank-Starling law of the heart' constitutes a fundamental cardiac property that has been appreciated for well over a century, it is still not known in muscle how the contractile apparatus transduces the information concerning sarcomere length to modulate ventricular pressure development.

  15. A Characteristic Particle Length

    CERN Document Server

    Roberts, Mark D

    2015-01-01

    It is argued that there are characteristic intervals associated with any particle that can be derived without reference to the speed of light $c$. Such intervals are inferred from zeros of wavefunctions which are solutions to the Schr\\"odinger equation. The characteristic length is $\\ell=\\beta^2\\hbar^2/(8Gm^3)$, where $\\beta=3.8\\dots$; this length might lead to observational effects on objects the size of a virus.

  16. β-Defensin genomic copy number does not influence the age of onset in Huntington's Disease

    NARCIS (Netherlands)

    Vittori, Angelica; Orth, Michael; Roos, Raymund A C; Outeiro, Tiago F; Giorgini, Flaviano; Hollox, Edward J; Kremer, Berry

    2013-01-01

    BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of a CAG triplet repeat tract in the huntingtin gene. While the length of this CAG expansion is the major determinant of the age of onset (AO), other genetic factors have also b

  17. Equilibrium CO bond lengths

    Science.gov (United States)

    Demaison, Jean; Császár, Attila G.

    2012-09-01

    Based on a sample of 38 molecules, 47 accurate equilibrium CO bond lengths have been collected and analyzed. These ultimate experimental (reEX), semiexperimental (reSE), and Born-Oppenheimer (reBO) equilibrium structures are compared to reBO estimates from two lower-level techniques of electronic structure theory, MP2(FC)/cc-pVQZ and B3LYP/6-311+G(3df,2pd). A linear relationship is found between the best equilibrium bond lengths and their MP2 or B3LYP estimates. These (and similar) linear relationships permit to estimate the CO bond length with an accuracy of 0.002 Å within the full range of 1.10-1.43 Å, corresponding to single, double, and triple CO bonds, for a large number of molecules. The variation of the CO bond length is qualitatively explained using the Atoms in Molecules method. In particular, a nice correlation is found between the CO bond length and the bond critical point density and it appears that the CO bond is at the same time covalent and ionic. Conditions which permit the computation of an accurate ab initio Born-Oppenheimer equilibrium structure are discussed. In particular, the core-core and core-valence correlation is investigated and it is shown to roughly increase with the bond length.

  18. Observations on oesophageal length.

    Science.gov (United States)

    Kalloor, G J; Deshpande, A H; Collis, J L

    1976-01-01

    The subject of oesophageal length is discussed. The great variations in the length of the oesophagus in individual patients is noted, and the practical use of its recognition in oesophageal surgery is stressed. An apprasial of the various methods available for this measurement is made; this includes the use of external chest measurement, endoscopic measurement, and the measurement of the level of the electrical mucosal potential change. Correlative studies of these various methods are made, and these show a very high degree of significance. These studies involved simultaneous measurement of external and internal oesophageal length in 26 patients without a hiatal hernia or gastro-oesophageal length in 26 patients without a hiatal hernia or gastro-oesophageal reflux symptoms, 42 patients with sliding type hiatal hernia, and 17 patients with a peptic stricture in association with hiatal hernia. The method of measuring oesophageal length by the use of the external chest measurement, that is, the distance between the lower incisor teeth and the xiphisternum, measured with the neck fully extended and the patient lying supine, is described in detail, its practical application in oesophageal surgery is illustrated, and its validity tested by internal measurements. The findings of this study demonstrate that the external chest measurement provides a mean of assessing the true static length of the oesophagus, corrected for the size of the individual. Images PMID:941114

  19. Late-onset Huntington disease with intermediate CAG repeats: true or false?

    NARCIS (Netherlands)

    Groen, J.L.; de Bie, R.M.A.; Foncke, E.M.J.; Roos, R.A.C.; Leenders, K.L.; Tijssen, M.A.J.

    2010-01-01

    Huntington disease (HD) is a neurodegenerative disorder associated with an expanded CAG trinucleotide repeat length in the huntingtin gene. 'Intermediate alleles' with 27 to 35 CAG repeats generally do not cause HD but are unstable upon germ-line transmission. Insights in CAG repeat mosaicism and en

  20. Late-onset Huntington disease with intermediate CAG repeats : true or false?

    NARCIS (Netherlands)

    Groen, Justus L.; de Bie, Rob M. A.; Foncke, Elisabeth M. J.; Roos, Raymund A. C.; Leenders, Klaus L.; Tijssen, Marina A. J.

    2010-01-01

    Huntington disease (HD) is a neurodegenerative disorder associated with an expanded CAG trinucleotide repeat length in the huntingtin gene. 'Intermediate alleles' with 27 to 35 CAG repeats generally do not cause HD but are unstable upon germ-line transmission. Insights in CAG repeat mosaicism and en

  1. Nutrients, foods, dietary patterns and telomere length: Update of epidemiological studies and randomized trials.

    Science.gov (United States)

    Freitas-Simoes, Tania-Marisa; Ros, Emilio; Sala-Vila, Aleix

    2016-04-01

    Identifying simple strategies to prevent or delay age-associated pathologies is a major public health concern. Attrition of telomeres, chromatin structures that help maintain genome stability, leads to cell death or senescence. Thus telomere length is a reliable hallmark of biological aging and the risk of developing age-related chronic diseases through common oxidation and inflammation mechanisms. Variability in telomere shortening that is independent of chronological age suggests that it is a modifiable factor, which may be explained in part by lifestyle variables such as smoking, adiposity, physical exercise, and diet. Here we summarize data from published studies focused on nutrition (nutrients, foods, and dietary patterns) and telomere length. Research on the topic is incipient and most data comes from epidemiologic studies, often cross-sectional in design. Consistent with well-known evidence of benefit or harm for chronic age-related diseases, dietary antioxidants and consumption of antioxidant-rich, plant-derived foods help maintain telomere length. In contrast, total and saturated fat intake and consumption of refined flour cereals, meat and meat products, and sugar-sweetened beverages relate to shorter telomeres. Data on alcohol and dairy products is controversial. There is evidence that adherence to the Mediterranean diet is associated with longer telomeres. Randomized clinical trials are limited to seafood-derived long-chain n-3 polyunsaturated fatty acids, with promising results. To fill the many gaps in our knowledge of the aging process and confirm nutrition as a useful tool to counteract biological aging more research is warranted, particularly observational studies using repeated measurements of telomere length and randomized trials of foods and dietary patterns with sequential telomere analyses.

  2. Does length of common limb influence remission of diabetes? Short-term results

    Directory of Open Access Journals (Sweden)

    Ramraj V Nagendra Gupta

    2016-01-01

    Full Text Available Background: Despite strict patient selection criteria, diabetes remission is not seen in all patients after gastric bypass. Can length of the common limb influence diabetes remission? Aim: To find if any correlation exists between the length of the common limb and remission of diabetes. Study Design: Prospective study. Materials and Methods: Twenty-five consecutive patients with Type II diabetes mellitus and a fasting C-peptide >1 ng/ml who underwent laparoscopic Roux-en-y gastric bypass were included. All patients had standard limb lengths and length of the common limb was measured in all patients. Patients were followed up and glycated haemoglobin (HbA1c was repeated at 6 months postoperatively. Pre- and postoperative HbA1c were then correlated with the lengths of common limb to look for any relation. Statistical Analysis: Descriptive and inferential statistical analysis, analysis of variance (ANOVA. Results: Of the 25 patients, 15 were females and 10 were males. The mean age was 44.16 years and the mean body mass index (BMI was 43.96 kg/m 2 . Preoperative HbA1c varied from 5.8 to 12.3%. Length of the common limb varied from 210 to 790 cm (mean 470.4 cm. HbA1c at 6 months ranged from 4.8 to 7.7% (mean 5.81%. On comparison of preoperative and 6 months postoperative HbA1c and correlating with the length of common limb, we found that patients with a common limb of length 600 cm length (P = 0.004. Conclusion: A shorter common limb does appear to have better chances of resolution of Type II diabetes mellitus in our study, thus paving the way for further studies.

  3. Role of androgen receptor CAG repeat polymorphism and X-inactivation in the manifestation of recurrent spontaneous abortions in Indian women.

    Directory of Open Access Journals (Sweden)

    Meka Aruna

    Full Text Available The aim of the present study was to investigate the role of CAG repeat polymorphism and X-chromosome Inactivation (XCI pattern in Recurrent Spontaneous Abortions among Indian women which has not been hitherto explored. 117 RSA cases and 224 Controls were included in the study. Cases were recruited from two different hospitals--Lakshmi Fertility Clinic, Nellore and Fernandez Maternity Hospital, Hyderabad. Controls were roughly matched for age, ethnicity and socioeconomic status. The CAG repeats of the Androgen Receptor gene were genotyped using a PCR-based assay and were analysed using the GeneMapper software to determine the CAG repeat length. XCI analysis was also carried out to assess the inactivation percentages. RSA cases had a significantly greater frequency of allele sizes in the polymorphic range above 19 repeats (p = 0.006, which is the median value of the controls, and in the biallelic mean range above 21 repeats (p = 0.002. We found no evidence of abnormal incidence of skewed X-inactivation. We conclude that longer CAG repeat lengths are associated with increased odds for RSA with statistical power estimated to be ∼90%.

  4. Alu repeats as markers for human population genetics

    Energy Technology Data Exchange (ETDEWEB)

    Batzer, M.A.; Alegria-Hartman, M. [Lawrence Livermore National Lab., CA (United States); Bazan, H. [Louisiana State Univ., New Orleans, LA (United States). Medical Center] [and others

    1993-09-01

    The Human-Specific (HS) subfamily of Alu sequences is comprised of a group of 500 nearly identical members which are almost exclusively restricted to the human genome. Individual subfamily members share an average of 97.9% nucleotide identity with each other and an average of 98.9% nucleotide identity with the HS subfamily consensus sequence. HS Alu family members are thought to be derived from a single source ``master`` gene, and have an average age of 2.8 million years. We have developed a Polymerase Chain Reaction (PCR) based assay using primers complementary to the 5 in. and 3 in. unique flanking DNA sequences from each HS Alu that allows the locus to be assayed for the presence or absence of an Alu repeat. Individual HS Alu sequences were found to be either monomorphic or dimorphic for the presence or absence of each repeat. The monomorphic HS Alu family members inserted in the human genome after the human/great ape divergence (which is thought to have occurred 4--6 million years ago), but before the radiation of modem man. The dimorphic HS Alu sequences inserted in the human genome after the radiation of modem man (within the last 200,000-one million years) and represent a unique source of information for human population genetics and forensic DNA analyses. These sites can be developed into Dimorphic Alu Sequence Tagged Sites (DASTS) for the Human Genome Project as well. HS Alu family member insertion dimorphism differs from other types of polymorphism (e.g. Variable Number of Tandem Repeat [VNTR] or Restriction Fragment Length Polymorphism [RFLP]) because individuals share HS Alu family member insertions based upon identity by descent from a common ancestor as a result of a single event which occurred one time within the human population. The VNTR and RFLP polymorphisms may arise multiple times within a population and are identical by state only.

  5. Mental rotation in intellectually gifted boys is affected by the androgen receptor CAG repeat polymorphism.

    Science.gov (United States)

    Durdiaková, Jaroslava; Lakatošová, Silvia; Kubranská, Aneta; Laznibatová, Jolana; Ficek, Andrej; Ostatníková, Daniela; Celec, Peter

    2013-08-01

    Testosterone was shown to organize brain and modulate cognitive functions. It is currently unknown whether mental rotation is also associated with prenatal testosterone exposure and testosterone-related genetic polymorphisms. The aim of our study was to analyze associations between mental rotation performance, the actual testosterone levels, the prenatal testosterone level (expressed as 2D:4D ratio) and the androgen receptor CAG repeat polymorphism in intellectually gifted boys. One hundred forty-seven boys aged 10-18 years with IQ>130 were enrolled. Saliva samples were collected and used for ELISA of actual levels of salivary testosterone. The 2D:4D finger length ratio as an indicator of prenatal testosterone was measured on both hands and averaged. Amthauer mental rotation test was used for the assessment of this spatial ability. The CAG repeat polymorphism in the androgen receptor gene was analyzed using PCR and capillary electrophoresis. Linear regression revealed that 2D:4D finger length ratio and the number of CAG repeats in the androgen receptor gene were associated with mental rotation. Actual levels of testosterone did not correlate significantly with mental rotation. Multivariate analysis of covariance revealed that after adjustment of age as a confounding variable, only the effect of the genetic polymorphism was significant. The results are in line with our previous genetic analysis of intellectually gifted boys showing the importance of CAG repeat polymorphism in the androgen receptor gene. Details of the interactions between androgen signaling, testosterone levels and its metabolism especially during the prenatal development of brain function remain to be elucidated. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Classifying stages of third molar development: crown length as a predictor for the mature root length.

    Science.gov (United States)

    Altalie, Salem; Thevissen, Patrick; Willems, Guy

    2015-01-01

    Multiple tooth development staging techniques were reported based on arbitrarily set borderlines between succeeding stages. Anatomic tooth features or predictions of future tooth part dimensions were described to identify the thresholds between the established stages. The need to predict mature tooth dimensions, while the tooth considered is still in development, is a drawback to use this staging technique for dental age estimations. Using the fully mature crown length as a predictor for the future root length could provide a tool for undisputable staging. The aim of this study was first to measure the crown and root length of fully mature third molars and second to investigate whether the crown length could be used as a predictor of the root length, in order to classify the observed root length as a proportion of the future mature root. The crown and root lengths of all present third molars were digitally measured on dental panoramic radiographs of 1,000 subjects. The included subjects were equally distributed in gender, and their age ranged between 22 and 40 years. Two occlusal borders, the cement enamel junction and the root apices, were defined as landmarks for standardized measurements. Regression models with root length as response and crown length as predictor were established and revealed low R (2) and high RMSE values. Due to the small explained variance by the prediction models and the high variation in prediction errors, the observed crown length cannot be used to predict the final root length of a developing third molar.

  7. Repeatability of Cryogenic Multilayer Insulation

    Science.gov (United States)

    Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

    2017-01-01

    Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between multiple identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five GRC provided coupons with 25 layers was shown to be +/- 8.4 whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0. A second group of 10 coupons have been fabricated by Yetispace and tested by Florida State University, through the first 4 tests, the repeatability has been shown to be +/- 16. Based on detailed statistical analysis, the data has been shown to be statistically significant.

  8. CAG Repeat Number in the Androgen Receptor Gene and Prostate Cancer.

    Science.gov (United States)

    Madjunkova, S; Eftimov, A; Georgiev, V; Petrovski, D; Dimovski, Aj; Plaseska-Karanfilska, D

    2012-06-01

    Prostate cancer (PC) is the second leading cause of cancer deaths in men. The effects of androgens on prostatic tissue are mediated by the androgen receptor (AR) gene. The 5' end of exon 1 of the AR gene includes a polymorphic CAG triplet repeat that numbers between 10 to 36 in the normal population. The length of the CAG repeats is inversely related to the transactivation function of the AR gene. There is controversy over association between short CAG repeat numbers in the AR gene and PC. This retrospective case-control study evaluates the possible effect of short CAG repeats on the AR gene in prostate cancer risk in Macedonian males. A total of 392 male subjects, 134 PC patients, 106 patients with benign prostatic hyperplasia (BPH) and 152 males from the general Macedonian population were enrolled in this study. The CAG repeat length was determined by fluorescent polymerase chain reaction (PCR) amplification of exon1 of the AR gene followed by capillary electrophoresis (CE) on a genetic analyzer. The mean repeat length in PC patients was 21.5 ± 2.65, in controls 22.28 ± 2.86 (p = 0.009) and in BPH patients 22.1 ± 2.52 (p = 0.038). Short CAG repeats (CAG repeat (CAG repeat length. These results suggest that reduced CAG repeat length may be associated with increased prostate cancer risk in Macedonian men.

  9. Effect of cycloplegia on axial length and anterior chamber depth measurements in children.

    Science.gov (United States)

    Cheung, Sin Wan; Chan, Rufina; Cheng, Roy Cs; Cho, Pauline

    2009-11-01

    Cycloplegia has been shown to have no effect on axial length measurement made with the IOLMaster in adults. The current study aimed at evaluating the effect of cycloplegia on axial length and anterior chamber depth (ACD) measurements made with the IOLMaster and an ultrasonic biometer in children. Pre- and post-cycloplegic axial length and ACD were measured with the IOLMaster followed by the Sonomed A-5500 in 31 children aged from seven to 15 years by the same examiner. The 95% limits of agreement (LoA) were determined, if there were no significant correlations found between the mean differences and their means. Seven subjects were excluded. Results from the remaining 24 subjects show that the effects of cycloplegia, instruments, and interaction between cycloplegia and instrument on axial length measurement were insignificant (repeated measure ANOVA F(1,23) 0.15). The 95% LoA in cycloplegia were better with the IOLMaster (-0.04 to 0.04 mm) than with the Sonomed A-5500 (-0.13 to 0.14 mm). The 95% LoA between the two instruments were similar with and without cycloplegia (pre-cycloplegia: -0.20 to 0.27 mm; post-cycloplegia: -0.17 to 0.22 mm). There was no significant interaction between cycloplegia and instrument in ACD measurement (repeated measure ANOVA F(1,23)= 0.85, p = 0.37), however, ACD was 0.05 to 0.06 mm shorter before cycloplegia (repeated measure ANOVA F(1,23)= 44.70, p Sonomed A-5500 were insignificant. In contrast, ACD measurement was significantly affected by cycloplegia and different instruments.

  10. Long CAG Repeat Sequence and Protein Expression of Androgen Receptor Considered as Prognostic Indicators in Male Breast Carcinoma

    OpenAIRE

    Yan-Ni Song; Jing-Shu Geng; Tong Liu; Zhen-Bin Zhong; Yang Liu; Bing-Shu Xia; Hong-Fei Ji; Xiao-Mei Li; Guo-Qiang Zhang; Yan-Lv Ren; Zhi-Gao Li; Da Pang

    2012-01-01

    BACKGROUND: The androgen receptor (AR) expression and the CAG repeat length within the AR gene appear to be involved in the carcinogenesis of male breast carcinoma (MBC). Although phenotypic differences have been observed between MBC and normal control group in AR gene, there is lack of correlation analysis between AR expression and CAG repeat length in MBC. The purpose of the study was to investigate the prognostic value of CAG repeat lengths and AR protein expression. METHODS: 81 tumor tiss...

  11. Activity of telomerase and telomeric length in Apis mellifera.

    Science.gov (United States)

    Korandová, Michala; Frydrychová, Radmila Čapková

    2016-06-01

    Telomerase is an enzyme that adds repeats of DNA sequences to the ends of chromosomes, thereby preventing their shortening. Telomerase activity is associated with proliferative status of cells, organismal development, and aging. We report an analysis of telomerase activity and telomere length in the honeybee, Apis mellifera. Telomerase activity was found to be regulated in a development and caste-specific manner. During the development of somatic tissues of larval drones and workers, telomerase activity declined to 10 % of its level in embryos and remained low during pupal and adult stages but was upregulated in testes of late pupae, where it reached 70 % of the embryo level. Upregulation of telomerase activity was observed in the ovaries of late pupal queens, reaching 160 % of the level in embryos. Compared to workers and drones, queens displayed higher levels of telomerase activity. In the third larval instar of queens, telomerase activity reached the embryo level, and an enormous increase was observed in adult brains of queens, showing a 70-fold increase compared to a brain of an adult worker. Southern hybridization of terminal TTAGG fragments revealed a high variability of telomeric length between different individuals, although the same pattern of hybridization signals was observed in different tissues of each individual.

  12. The association between global DNA methylation and telomere length in a longitudinal study of boilermakers.

    Science.gov (United States)

    Wong, Jason Y Y; De Vivo, Immaculata; Lin, Xihong; Grashow, Rachel; Cavallari, Jennifer; Christiani, David C

    2014-04-01

    The objectives of this study were to determine if global DNA methylation, as reflected in LINE-1 and Alu elements, is associated with telomere length and whether it modifies the rate of telomeric change. A repeated-measures longitudinal study was performed with a panel of 87 boilermaker subjects. The follow-up period was 29 months. LINE-1 and Alu methylation was determined using pyrosequencing. Leukocyte relative telomere length was assessed via real-time qPCR. Linear-mixed models were used to estimate the association between DNA methylation and telomere length. A structural equation model (SEM) was used to explore the hypothesized relationship between DNA methylation, proxies of particulate matter exposure, and telomere length at baseline. There appeared to be a positive association between both LINE-1 and Alu methylation levels, and telomere length. For every incremental increase in LINE-1 methylation, there was a statistically significant 1.0 × 10(-1) (95% CI: 4.6 × 10(-2), 1.5 × 10(-1), P telomere length, controlling for age at baseline, current and past smoking status, work history, BMI (log kg/m(2) ) and leukocyte differentials. Furthermore, for every incremental increase in Alu methylation, there was a statistically significant 6.2 × 10(-2) (95% CI: 1.0 × 10(-2), 1.1 × 10(-1), P = 0.02) unit increase in relative telomere length. The interaction between LINE-1 methylation and follow-up time was statistically significant with an estimate -9.8 × 10(-3) (95% CI: -1.8 × 10(-2), -1.9 × 10(-3), P = 0.02); suggesting that the rate of telomeric change was modified by the degree of LINE-1 methylation. No statistically significant association was found between the cumulative PM exposure construct, with global DNA methylation and telomere length at baseline.

  13. Frequency Bandwidth of Half-Wave Impedance Repeater

    Directory of Open Access Journals (Sweden)

    Marek Dvorsky

    2012-01-01

    Full Text Available This article brings in the second part general information about half-wave impedance repeater. The third part describes the basic functional principles of the half-wave impedance repeater using Smith chart. The main attention is focused in part four on the derivation of repeater frequency bandwidth depending on characteristics and load impedance of unknown feeder line. Derived dependences are based on the elementary features of the feeder lines with specific length. The described functionality is proved in part 4.3 by measurement of transformed impedance using vector several unbalanced feeder lines and network analyzer VNWA3+.

  14. GFP-based fluorescence assay for CAG repeat instability in cultured human cells.

    Directory of Open Access Journals (Sweden)

    Beatriz A Santillan

    Full Text Available Trinucleotide repeats can be highly unstable, mutating far more frequently than point mutations. Repeats typically mutate by addition or loss of units of the repeat. CAG repeat expansions in humans trigger neurological diseases that include myotonic dystrophy, Huntington disease, and several spinocerebellar ataxias. In human cells, diverse mechanisms promote CAG repeat instability, and in mice, the mechanisms of instability are varied and tissue-dependent. Dissection of mechanistic complexity and discovery of potential therapeutics necessitates quantitative and scalable screens for repeat mutation. We describe a GFP-based assay for screening modifiers of CAG repeat instability in human cells. The assay exploits an engineered intronic CAG repeat tract that interferes with expression of an inducible GFP minigene. Like the phenotypes of many trinucleotide repeat disorders, we find that GFP function is impaired by repeat expansion, in a length-dependent manner. The intensity of fluorescence varies inversely with repeat length, allowing estimates of repeat tract changes in live cells. We validate the assay using transcription through the repeat and engineered CAG-specific nucleases, which have previously been reported to induce CAG repeat instability. The assay is relatively fast and should be adaptable to large-scale screens of chemical and shRNA libraries.

  15. Telomere shortening unrelated to smoking, body weight, physical activity, and alcohol intake: 4,576 general population individuals with repeat measurements 10 years apart.

    Directory of Open Access Journals (Sweden)

    Maren Weischer

    2014-03-01

    Full Text Available Cross-sectional studies have associated short telomere length with smoking, body weight, physical activity, and possibly alcohol intake; however, whether these associations are due to confounding is unknown. We tested these hypotheses in 4,576 individuals from the general population cross-sectionally, and with repeat measurement of relative telomere length 10 years apart. We also tested whether change in telomere length is associated with mortality and morbidity in the general population. Relative telomere length was measured with quantitative polymerase chain reaction. Cross-sectionally at the first examination, short telomere length was associated with increased age (P for trend across quartiles = 3 × 10(-77, current smoking (P = 8 × 10(-3, increased body mass index (P = 7 × 10(-14, physical inactivity (P = 4 × 10(-17, but not with increased alcohol intake (P = 0.10. At the second examination 10 years later, 56% of participants had lost and 44% gained telomere length with a mean loss of 193 basepairs. Change in leukocyte telomere length during 10 years was associated inversely with baseline telomere length (P<1 × 10(-300 and age at baseline (P = 1 × 10(-27, but not with baseline or 10-year inter-observational tobacco consumption, body weight, physical activity, or alcohol intake. Prospectively during a further 10 years follow-up after the second examination, quartiles of telomere length change did not associate with risk of all-cause mortality, cancer, chronic obstructive pulmonary disease, diabetes mellitus, ischemic cerebrovascular disease, or ischemic heart disease. In conclusion, smoking, increased body weight, and physical inactivity were associated with short telomere length cross-sectionally, but not with telomere length change during 10 years observation, and alcohol intake was associated with neither. Also, change in telomere length did not associate prospectively with mortality or morbidity in the general population.

  16. The association of CGG repeats in the FMR1 gene and timing of natural menopause

    NARCIS (Netherlands)

    Voorhuis, M.; Onland-Moret, N. C.; Fauser, B. C. J. M.; van Amstel, H. K. Ploos; van der Schouw, Y. T.; Broekmans, F. J.

    2013-01-01

    Is there an association between the number of CGG repeats in the FMR1 gene in the normal and intermediate range and age at natural menopause? The number of CGG repeats in the normal and intermediate range in the FMR1 gene was not associated with age at natural menopause. Excessive triple CGG repeats

  17. CAG trinucleotide RNA repeats interact with RNA-binding proteins

    Energy Technology Data Exchange (ETDEWEB)

    McLaughlin, B.A.; Eberwine, J.; Spencer, C. [Univ. of Pennsylvania, Philadelphia, PA (United States)

    1996-09-01

    Genes associated with several neurological diseases are characterized by the presence of an abnormally long trinucleotide repeat sequence. By way of example, Huntington`s disease (HD), is characterized by selective neuronal degeneration associated with the expansion of a polyglutamine-encoding CAG tract. Normally, this CAG tract is comprised of 11-34 repeats, but in HD it is expanded to >37 repeats in affected individuals. The mechanism by which CAG repeats cause neuronal degeneration is unknown, but it has been speculated that the expansion primarily causes abnormal protein functioning, which in turn causes HD pathology. Other mechanisms, however, have not been ruled out. Interactions between RNA and RNA-binding proteins have previously been shown to play a role in the expression of several eukaryotic genes. Herein, we report the association of cytoplasmic proteins with normal length and extended CAG repeats, using gel shift and LJV crosslinking assays. Cytoplasmic protein extracts from several rat brain regions, including the striatum and cortex, sites of neuronal degeneration in HD, contain a 63-kD RNA-binding protein that specifically interacts with these CAG-repeat sequences. These protein-RNA interactions are dependent on the length of the CAG repeat, with longer repeats binding substantially more protein. Two CAG repeat-binding proteins are present in human cortex and striatum; one comigrates with the rat protein at 63 kD, while the other migrates at 49 kD. These data suggest mechanisms by which RNA-binding proteins may be involved in the pathological course of trinucleotide repeat-associated neurological diseases. 47 refs., 5 figs.

  18. Correlation of inter-locus polyglutamine toxicity with CAG•CTG triplet repeat expandability and flanking genomic DNA GC content.

    Directory of Open Access Journals (Sweden)

    Colm E Nestor

    Full Text Available Dynamic expansions of toxic polyglutamine (polyQ-encoding CAG repeats in ubiquitously expressed, but otherwise unrelated, genes cause a number of late-onset progressive neurodegenerative disorders, including Huntington disease and the spinocerebellar ataxias. As polyQ toxicity in these disorders increases with repeat length, the intergenerational expansion of unstable CAG repeats leads to anticipation, an earlier age-at-onset in successive generations. Crucially, disease associated alleles are also somatically unstable and continue to expand throughout the lifetime of the individual. Interestingly, the inherited polyQ length mediating a specific age-at-onset of symptoms varies markedly between disorders. It is widely assumed that these inter-locus differences in polyQ toxicity are mediated by protein context effects. Previously, we demonstrated that the tendency of expanded CAG•CTG repeats to undergo further intergenerational expansion (their 'expandability' also differs between disorders and these effects are strongly correlated with the GC content of the genomic flanking DNA. Here we show that the inter-locus toxicity of the expanded polyQ tracts of these disorders also correlates with both the expandability of the underlying CAG repeat and the GC content of the genomic DNA flanking sequences. Inter-locus polyQ toxicity does not correlate with properties of the mRNA or protein sequences, with polyQ location within the gene or protein, or steady state transcript levels in the brain. These data suggest that the observed inter-locus differences in polyQ toxicity are not mediated solely by protein context effects, but that genomic context is also important, an effect that may be mediated by modifying the rate at which somatic expansion of the DNA delivers proteins to their cytotoxic state.

  19. The association between leukocyte telomere length and cigarette smoking, dietary and physical variables, and risk of prostate cancer.

    Science.gov (United States)

    Mirabello, Lisa; Huang, Wen-Yi; Wong, Jason Y Y; Chatterjee, Nilanjan; Reding, Douglas; Crawford, E David; De Vivo, Immaculata; Hayes, Richard B; Savage, Sharon A

    2009-08-01

    Telomeres consist of nucleotide repeats and a protein complex at chromosome ends that are essential to maintaining chromosomal integrity. Several studies have suggested that subjects with shorter telomeres are at increased risk of bladder and lung cancer. In comparison to normal tissues, telomeres are shorter in high-grade intraepithelial neoplasia and prostate cancer. We examined prostate cancer risk associated with relative telomere length as determined by quantitative PCR on prediagnostic buffy coat DNA isolated from 612 advanced prostate cancer cases and 1049 age-matched, cancer-free controls from the PLCO Cancer Screening Trial. Telomere length was analyzed as both a continuous and a categorical variable with adjustment for potential confounders. Statistically significant inverse correlations between telomere length, age and smoking status were observed in cases and controls. Telomere length was not associated with prostate cancer risk (at the median, OR = 0.85, 95% CI: 0.67, 1.08); associations were similar when telomere length was evaluated as a continuous variable or by quartiles. The relationships between telomere length and inflammation-related factors, diet, exercise, body mass index, and other lifestyle variables were explored since many of these have previously been associated with shorter telomeres. Healthy lifestyle factors (i.e., lower BMI, more exercise, tobacco abstinence, diets high in fruit and vegetables) tended to be associated with greater telomere length. This study found no statistically significant association between leukocyte telomere length and advanced prostate cancer risk. However, correlations of telomere length with healthy lifestyles were noted, suggesting the role of these factors in telomere biology maintenance and potentially impacting overall health status.

  20. Relativistic length agony continued

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    Redžić D.V.

    2014-01-01

    Full Text Available We made an attempt to remedy recent confusing treatments of some basic relativistic concepts and results. Following the argument presented in an earlier paper (Redžić 2008b, we discussed the misconceptions that are recurrent points in the literature devoted to teaching relativity such as: there is no change in the object in Special Relativity, illusory character of relativistic length contraction, stresses and strains induced by Lorentz contraction, and related issues. We gave several examples of the traps of everyday language that lurk in Special Relativity. To remove a possible conceptual and terminological muddle, we made a distinction between the relativistic length reduction and relativistic FitzGerald-Lorentz contraction, corresponding to a passive and an active aspect of length contraction, respectively; we pointed out that both aspects have fundamental dynamical contents. As an illustration of our considerations, we discussed briefly the Dewan-Beran-Bell spaceship paradox and the ‘pole in a barn’ paradox. [Projekat Ministarstva nauke Republike Srbije, br. 171028

  1. Ground Wood Fiber Length Distributions

    OpenAIRE

    Lauri Ilmari Salminen; Sari Liukkonen; Alava, Mikko J.

    2014-01-01

    This study considers ground wood fiber length distributions arising from pilot grindings. The empirical fiber length distributions appear to be independent of wood fiber length as well as feeding velocity. In terms of mathematics the fiber fragment distributions of ground wood pulp combine an exponential distribution for high-length fragments and a power-law distribution for smaller lengths. This implies that the fiber length distribution is influenced by the stone surface. A fragmentation-ba...

  2. Preferentially quantized linker DNA lengths in Saccharomyces cerevisiae.

    Science.gov (United States)

    Wang, Ji-Ping; Fondufe-Mittendorf, Yvonne; Xi, Liqun; Tsai, Guei-Feng; Segal, Eran; Widom, Jonathan

    2008-09-12

    The exact lengths of linker DNAs connecting adjacent nucleosomes specify the intrinsic three-dimensional structures of eukaryotic chromatin fibers. Some studies suggest that linker DNA lengths preferentially occur at certain quantized values, differing one from another by integral multiples of the DNA helical repeat, approximately 10 bp; however, studies in the literature are inconsistent. Here, we investigate linker DNA length distributions in the yeast Saccharomyces cerevisiae genome, using two novel methods: a Fourier analysis of genomic dinucleotide periodicities adjacent to experimentally mapped nucleosomes and a duration hidden Markov model applied to experimentally defined dinucleosomes. Both methods reveal that linker DNA lengths in yeast are preferentially periodic at the DNA helical repeat ( approximately 10 bp), obeying the forms 10n+5 bp (integer n). This 10 bp periodicity implies an ordered superhelical intrinsic structure for the average chromatin fiber in yeast.

  3. Preferentially quantized linker DNA lengths in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Ji-Ping Wang

    Full Text Available The exact lengths of linker DNAs connecting adjacent nucleosomes specify the intrinsic three-dimensional structures of eukaryotic chromatin fibers. Some studies suggest that linker DNA lengths preferentially occur at certain quantized values, differing one from another by integral multiples of the DNA helical repeat, approximately 10 bp; however, studies in the literature are inconsistent. Here, we investigate linker DNA length distributions in the yeast Saccharomyces cerevisiae genome, using two novel methods: a Fourier analysis of genomic dinucleotide periodicities adjacent to experimentally mapped nucleosomes and a duration hidden Markov model applied to experimentally defined dinucleosomes. Both methods reveal that linker DNA lengths in yeast are preferentially periodic at the DNA helical repeat ( approximately 10 bp, obeying the forms 10n+5 bp (integer n. This 10 bp periodicity implies an ordered superhelical intrinsic structure for the average chromatin fiber in yeast.

  4. Long CAG repeat sequence and protein expression of androgen receptor considered as prognostic indicators in male breast carcinoma.

    Directory of Open Access Journals (Sweden)

    Yan-Ni Song

    Full Text Available BACKGROUND: The androgen receptor (AR expression and the CAG repeat length within the AR gene appear to be involved in the carcinogenesis of male breast carcinoma (MBC. Although phenotypic differences have been observed between MBC and normal control group in AR gene, there is lack of correlation analysis between AR expression and CAG repeat length in MBC. The purpose of the study was to investigate the prognostic value of CAG repeat lengths and AR protein expression. METHODS: 81 tumor tissues were used for immunostaining for AR expression and CAG repeat length determination and 80 normal controls were analyzed with CAG repeat length in AR gene. The CAG repeat length and AR expression were analyzed in relation to clinicopathological factors and prognostic indicators. RESULTS: AR gene in many MBCs has long CAG repeat sequence compared with that in control group (P = 0.001 and controls are more likely to exhibit short CAG repeat sequence than MBCs. There was statistically significant difference in long CAG repeat sequence between AR status for MBC patients (P = 0.004. The presence of long CAG repeat sequence and AR-positive expression were associated with shorter survival of MBC patients (CAG repeat: P = 0.050 for 5y-OS; P = 0.035 for 5y-DFS AR status: P = 0.048 for 5y-OS; P = 0.029 for 5y-DFS, respectively. CONCLUSION: The CAG repeat length within the AR gene might be one useful molecular biomarker to identify males at increased risk of breast cancer development. The presence of long CAG repeat sequence and AR protein expression were in relation to survival of MBC patients. The CAG repeat length and AR expression were two independent prognostic indicators in MBC patients.

  5. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund

    2006-08-01

    Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

  6. A method for the incremental expansion of polyglutamine repeats in recombinant proteins.

    Science.gov (United States)

    Robertson, Amy L; Bottomley, Stephen P

    2013-01-01

    The polyglutamine diseases are caused by the expansion of CAG repeats. A key step in understanding the disease mechanisms, at the DNA and protein level, is the ability to produce recombinant proteins with specific length glutamine tracts which is a time-consuming first step in setting up in vitro systems to study the effects of polyglutamine expansion. Described here is a PCR-based method for the amplification of CAG repeats, which we used to incrementally extend CAG length by 3-5 repeats per cycle. This method could be translated into various contexts where amplification of repeating elements is necessary.

  7. Analysis of tandem repeats in the genome of Chinese shrimp Fenneropenaeus chinensis

    Institute of Scientific and Technical Information of China (English)

    KONG Jie; GAO Huan

    2005-01-01

    Through random sequencing, we found a total of 884000 base-pairs (bp) of random genomic sequences in the genome of Chinese shrimp (Fenneropenaeus chinensis). Using bio-soft Tandem Repeat Finder (TRF) software, 2159 tandem repeats were found, in which there were 1714 microsatellites and 445 minisatellites, accounting for 79.4% and 20.6% of repeat sequences, respectively. The cumulative length of repeat sequences was found to be 116685 bp, accounting for 13.2% of the total DNA sequence; the cumulative length of microsatellites occupied 9.78% of the total DNA sequence, and that of minisatellites occupied 3.42%. In decreasing order, the 20 most abundant repeat sequence classes were as follows: AT (557), AC (471), AG (274), AAT (92), A (56), AAG (28), ATC (27), ATAG (27), AGG (18), ACT (15), C (11), AAC (11), ACAT (11), CAGA (10), AGAA (9), AGGG (7), CAAA (7), CGCA (6), ATAA (6), AGAGAA (6). Dinucleotide repeats, not only in the aspect of the number, but also in cumulative length, were the preponderant repeat type. There were few classes and low copy numbers of repeat units of the pentanucleotide repeat type, which included only three classes: AGAGA, GAGGC and AAAGA. The classes and copy numbers of heptanucleotide, eleven-nucleotide and thirteen-nucleotide primer-number-composed repeats were distinctly less than that of repeat types beside them.

  8. Systematic exchanges between nucleotides: Genomic swinger repeats and swinger transcription in human mitochondria.

    Science.gov (United States)

    Seligmann, Hervé

    2015-11-07

    Chargaff׳s second parity rule, quasi-equal single strand frequencies for complementary nucleotides, presumably results from insertion of repeats and inverted repeats during sequence genesis. Vertebrate mitogenomes escape this rule because repeats are counterselected: their hybridization produces loop bulges whose deletion is deleterious. Some DNA/RNA sequences match mitogenomes only after assuming one among 23 systematic nucleotide exchanges (swinger DNA/RNA: nine symmetric, e.g. A ↔ C; and 14 asymmetric, e.g. A → C → G → A). Swinger-transformed repeats do not hybridize, escaping selection against deletions due to bulge formation. Blast analyses of the human mitogenome detect swinger repeats for all 23 swinger types, more than in randomized sequences with identical length and nucleotide contents. Mean genomic swinger repeat lengths increase with observed human swinger RNA frequencies: swinger repeat and swinger RNA productions appear linked, perhaps by swinger RNA retrotranscription. Mean swinger repeat lengths are proportional to reading frame retrievability, post-swinger transformation, by the natural circular code. Genomic swinger repeats confirm at genomic level, independently of swinger RNA detection, occurrence of swinger polymerizations. They suggest that repeats, and swinger repeats in particular, contribute to genome genesis.

  9. Safety of Repeated Yttrium-90 Radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Lam, Marnix G. E. H.; Louie, John D. [Stanford University School of Medicine, Division of Interventional Radiology (United States); Iagaru, Andrei H.; Goris, Michael L. [Stanford University School of Medicine, Division of Nuclear Medicine (United States); Sze, Daniel Y., E-mail: dansze@stanford.edu [Stanford University School of Medicine, Division of Interventional Radiology (United States)

    2013-10-15

    Purpose: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. Methods: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Results: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). Conclusion: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.

  10. discouraged by queue length

    Directory of Open Access Journals (Sweden)

    P. R. Parthasarathy

    2001-01-01

    Full Text Available The transient solution is obtained analytically using continued fractions for a state-dependent birth-death queue in which potential customers are discouraged by the queue length. This queueing system is then compared with the well-known infinite server queueing system which has the same steady state solution as the model under consideration, whereas their transient solutions are different. A natural measure of speed of convergence of the mean number in the system to its stationarity is also computed.

  11. PILER-CR: Fast and accurate identification of CRISPR repeats

    Directory of Open Access Journals (Sweden)

    Edgar Robert C

    2007-01-01

    Full Text Available Abstract Background Sequencing of prokaryotic genomes has recently revealed the presence of CRISPR elements: short, highly conserved repeats separated by unique sequences of similar length. The distinctive sequence signature of CRISPR repeats can be found using general-purpose repeat- or pattern-finding software tools. However, the output of such tools is not always ideal for studying these repeats, and significant effort is sometimes needed to build additional tools and perform manual analysis of the output. Results We present PILER-CR, a program specifically designed for the identification and analysis of CRISPR repeats. The program executes rapidly, completing a 5 Mb genome in around 5 seconds on a current desktop computer. We validate the algorithm by manual curation and by comparison with published surveys of these repeats, finding that PILER-CR has both high sensitivity and high specificity. We also present a catalogue of putative CRISPR repeats identified in a comprehensive analysis of 346 prokaryotic genomes. Conclusion PILER-CR is a useful tool for rapid identification and classification of CRISPR repeats. The software is donated to the public domain. Source code and a Linux binary are freely available at http://www.drive5.com/pilercr.

  12. Reduced fetal telomere length in gestational diabetes.

    Directory of Open Access Journals (Sweden)

    Jian Xu

    Full Text Available Gestational diabetes mellitus (GDM is an important complication of pregnancy that poses significant threats to women and their offspring. Telomere length shortens as cellular damage increases and is associated with metabolic diseases. Telomere length in fetal leucocytes was determined in 82 infants of women with GDM (N = 82 and 65 normal pregnant women (N = 65. Women with preeclampsia (N = 45 and gestational hypertension (N = 23 were also studied. In the GDM group, telomere length was significantly shorter than normal pregnancy (P = 0.028, but there were no significant differences in fetal telomere length between preeclampsia and normal pregnancy (P = 0.841 and between gestational hypertension and normal pregnancy (P = 0.561. Regression analysis revealed that fetal telomere length was significantly associated with intrauterine exposure to GDM (P = 0.027 after adjustment for maternal age, gestational age at delivery, birth weight and fetal gender. Shortened telomere length may increase the risk of metabolic diseases in adulthood of GDM offspring.

  13. Short telomere length and breast cancer risk: a study in sister sets.

    Science.gov (United States)

    Shen, Jing; Terry, Mary Beth; Gurvich, Irina; Liao, Yuyan; Senie, Ruby T; Santella, Regina M

    2007-06-01

    Telomeres consist of a tandem repeats of the sequence TTAGGG at the ends of chromosomes and play a key role in the maintenance of chromosomal stability. Previous studies indicated that short telomeres are associated with increased risk for human bladder, head and neck, lung, and renal cell cancer. We investigated the association between white blood cell telomere length and breast cancer risk among 268 family sets (287 breast cancer cases and 350 sister controls). Telomere length was assessed by quantitative PCR. The mean telomere length was shorter in cases (mean, 0.70; range, 0.03-1.95) than in unaffected control sisters (mean, 0.74; range, 0.03-2.29), but no significant difference was observed (P = 0.11). When subjects were categorized according to the median telomere length in controls (0.70), affected sisters had shorter telomeres compared with unaffected sisters after adjusting for age at blood donation and smoking status [odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.9-1.8], but the association was not statistically significant. The association by quartile of telomere length (Q4 shortest versus Q1 longest) also supported an increase in risk from shorter telomere length, although the association was not statistically significant (OR, 1.6; 95% CI, 0.9-2.7). This association was more pronounced among premenopausal women (OR, 2.1; 95% CI, 0.8-5.5) than postmenopausal women (OR, 1.3; 95% CI, 0.5-3.6 for Q4 versus Q1). If these associations are replicated in larger studies, they provide modest epidemiologic evidence that shortened telomere length may be associated with breast cancer risk.

  14. DWI Repeaters and Non-Repeaters: A Comparison.

    Science.gov (United States)

    Weeber, Stan

    1981-01-01

    Discussed how driving-while-intoxicated (DWI) repeaters differed signigicantly from nonrepeaters on 4 of 23 variables tested. Repeaters were more likely to have zero or two dependent children, attend church frequently, drink occasionally and have one or more arrests for public intoxication. (Author)

  15. To Repeat or Not to Repeat a Course

    Science.gov (United States)

    Armstrong, Michael J.; Biktimirov, Ernest N.

    2013-01-01

    The difficult transition from high school to university means that many students need to repeat (retake) 1 or more of their university courses. The authors examine the performance of students repeating first-year core courses in an undergraduate business program. They used data from university records for 116 students who took a total of 232…

  16. Distance and Cable Length Measurement System

    Directory of Open Access Journals (Sweden)

    Jonay Toledo

    2009-12-01

    Full Text Available A simple, economic and successful design for distance and cable length detection is presented. The measurement system is based on the continuous repetition of a pulse that endlessly travels along the distance to be detected. There is a pulse repeater at both ends of the distance or cable to be measured. The endless repetition of the pulse generates a frequency that varies almost inversely with the distance to be measured. The resolution and distance or cable length range could be adjusted by varying the repetition time delay introduced at both ends and the measurement time. With this design a distance can be measured with centimeter resolution using electronic system with microsecond resolution, simplifying classical time of flight designs which require electronics with picosecond resolution. This design was also applied to position measurement.

  17. Distance and Cable Length Measurement System

    Science.gov (United States)

    Hernández, Sergio Elias; Acosta, Leopoldo; Toledo, Jonay

    2009-01-01

    A simple, economic and successful design for distance and cable length detection is presented. The measurement system is based on the continuous repetition of a pulse that endlessly travels along the distance to be detected. There is a pulse repeater at both ends of the distance or cable to be measured. The endless repetition of the pulse generates a frequency that varies almost inversely with the distance to be measured. The resolution and distance or cable length range could be adjusted by varying the repetition time delay introduced at both ends and the measurement time. With this design a distance can be measured with centimeter resolution using electronic system with microsecond resolution, simplifying classical time of flight designs which require electronics with picosecond resolution. This design was also applied to position measurement. PMID:22303169

  18. A Novel Algorithm for Finding Interspersed Repeat Regions

    Institute of Scientific and Technical Information of China (English)

    Dongdong Li; Zhengzhi Wang; Qingshan Ni

    2004-01-01

    The analysis of repeats in the DNA sequences is an important subject in bioinformatics. In this paper, we propose a novel projection-assemble algorithm to find unknown interspersed repeats in DNA sequences. The algorithm employs random projection algorithm to obtain a candidate fragment set, and exhaustive search algorithm to search each pair of fragments from the candidate fragment set to find potential linkage, and then assemble them together. The complexity of our projection-assemble algorithm is nearly linear to the length of the genome sequence, and its memory usage is limited by the hardware. We tested our algorithm with both simulated data and real biology data, and the results show that our projection-assemble algorithm is efficient. By means of this algorithm, we found an un-labeled repeat region that occurs five times in Escherichia coli genome, with its length more than 5,000 bp, and a mismatch probability less than 4%.

  19. Ataxin-2 intermediate-length polyglutamine: a possible risk factor for Chinese patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Chen, Yongping; Huang, Rui; Yang, Yuan; Chen, Ke; Song, Wei; Pan, Pinglei; Li, Jianpeng; Shang, Hui-Fang

    2011-10-01

    Intermediate-length polyglutamine (polyQ) expansions in the ataxin-2 (ATXN2) gene have recently been identified as a risk factor for sporadic amyotrophic lateral sclerosis (SALS). Our study aims to analyze cytosine, adenine, guanine (CAG)n expansions in the ATXN2 gene among Chinese patients with SALS. All patients diagnosed with adult-onset sporadic amyotrophic lateral sclerosis (ALS) were consecutively followed up, and their clinical characteristics were collected. To measure the repeat length of ATXN2 polyQ, fluorescence-polymerase chain reaction products were analyzed on a 3100-Avant Genetic Analyzer Applied Biosystem (Foster City, CA, USA) using the ROC-500 size standard. Three hundred forty-five patients with SALS were studied. The mean age of onset was 51.38 ± 12.45 years. ATXN2 polyQ with a repeat length greater than 27 was found to be weakly associated with amyotrophic lateral sclerosis in our study. There was no significant difference in mean age of onset, gender, and onset site between the group of SALS patients with and without ATXN2 polyQ expansion greater than 27. Our finding provides evidence that the ATXN2 polyQ expansion greater than 27 might be a risk factor for Chinese SALS patients.

  20. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  1. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  2. Exact Tandem Repeats Analyzer (E-TRA): A new program for DNA sequence mining

    Indian Academy of Sciences (India)

    Mehmet Karaca; Mehmet Bilgen; A. Naci Onus; Ayse Gul Ince; Safinaz Y. Elmasulu

    2005-04-01

    Exact Tandem Repeats Analyzer 1.0 (E-TRA) combines sequence motif searches with keywords such as ‘organs’, ‘tissues’, ‘cell lines’ and ‘development stages’ for finding simple exact tandem repeats as well as non-simple repeats. E-TRA has several advanced repeat search parameters/options compared to other repeat finder programs as it not only accepts GenBank, FASTA and expressed sequence tags (EST) sequence files, but also does analysis of multiple files with multiple sequences. The minimum and maximum tandem repeat motif lengths that E-TRA finds vary from one to one thousand. Advanced user defined parameters/options let the researchers use different minimum motif repeats search criteria for varying motif lengths simultaneously. One of the most interesting features of genomes is the presence of relatively short tandem repeats (TRs). These repeated DNA sequences are found in both prokaryotes and eukaryotes, distributed almost at random throughout the genome. Some of the tandem repeats play important roles in the regulation of gene expression whereas others do not have any known biological function as yet. Nevertheless, they have proven to be very beneficial in DNA profiling and genetic linkage analysis studies. To demonstrate the use of E-TRA, we used 5,465,605 human EST sequences derived from 18,814,550 GenBank EST sequences. Our results indicated that 12.44% (679,800) of the human EST sequences contained simple and non-simple repeat string patterns varying from one to 126 nucleotides in length. The results also revealed that human organs, tissues, cell lines and different developmental stages differed in number of repeats as well as repeat composition, indicating that the distribution of expressed tandem repeats among tissues or organs are not random, thus differing from the un-transcribed repeats found in genomes.

  3. All-photonic quantum repeaters

    Science.gov (United States)

    Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2015-01-01

    Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

  4. Growth standardized values and curves based on weight for length/height,body mass index for Chinese children under 7 years of age%中国七岁以下儿童身长/身高的体重和体块指数的生长标准值及标准化生长曲线

    Institute of Scientific and Technical Information of China (English)

    首都儿科研究所; 九市儿童体格发育调查协作组

    2009-01-01

    目的 制定中国7岁以下儿童身长/身高的体重、体块指数(BMI)的生长标准值及标准化生长曲线.方法 选择"2005年九市儿童体格发育调查"中69 622名城区7岁以下儿童的身长/身高、体重测量值,采用LMS法分别建立身长的体重和BMI模型.将3岁后身高加上0.7 cm与身长对接,构建统一身长的体重LMS模型,数据拟合后可将身长减去0.7 cm转化为身高的体蕈.BMI采取"身长BMI"和"身高BMI"分别独立拟合的方法,将身高加上0.7 cm计算"身长BMI",在整个年龄段拟合"身长BMI"LMS模型,类似地可建立"身高BMI"模型.曲线的拟合效果评价采用拟合优度X2检验.结果 制定出中国儿童45~105 cm身长的体重、65~125 cm身高的体重、0~3岁年龄的BMI(由身长计算)、2~7岁年龄的BMI(由身高计算)的按百分位数及标准差单位的生长标准值及标准化生长曲线图.该参照标准总体上略高于世界卫生组织新标准,而略低于美国疾控中心2000年修订标准(CDC2000).结论 本研究制定的身长/身高的体重及BMI标准具有国家代表性,可在全国范围内用于儿童生长监测与营养评估.%Objective To construct the growth standardized data and curves based on weight for length/height,body mass index (BMI) for Chinese children under the age of 7 years.Methods The fourth national growth survey of children under 7 years of age in the nine cities of China was performed in 2005 and from this survey,data of the 69 622 urban healthy children were used to set up the database for weight for length/height (length was measured for children under 3 years of age) and BMI.Measurement data were ascribed to rigorous methods of data collection and standardized procedures across study sites.Models of weight for length/height and BMI were established by the LMS method,respectively;0.7 cm was added to the height values (3 to 7 years),then weight for length/height were fitted by the single model,and after the

  5. Longer leukocyte telomere length in Costa Rica's Nicoya Peninsula: a population-based study.

    Science.gov (United States)

    Rehkopf, David H; Dow, William H; Rosero-Bixby, Luis; Lin, Jue; Epel, Elissa S; Blackburn, Elizabeth H

    2013-11-01

    Studies in humans suggest that leukocyte telomere length may act as a marker of biological aging. We investigated whether individuals in the Nicoya region of Costa Rica, known for exceptional longevity, had longer telomere length than those in other parts of the country. After controlling for age, age squared, rurality, rainy season and gender, the mean leukocyte telomere length in Nicoya was substantially longer (81 base pairs, ptelomere length that characterizes this unique region does not appear to be explainable by traditional behavioral and biological risk factors. More detailed examination of mean leukocyte telomere length by age shows that the regional telomere length difference declines at older ages.

  6. Gain of Toxicity from ALS/FTD-Linked Repeat Expansions in C9ORF72 Is Alleviated by Antisense Oligonucleotides Targeting GGGGCC-Containing RNAs.

    Science.gov (United States)

    Jiang, Jie; Zhu, Qiang; Gendron, Tania F; Saberi, Shahram; McAlonis-Downes, Melissa; Seelman, Amanda; Stauffer, Jennifer E; Jafar-Nejad, Paymaan; Drenner, Kevin; Schulte, Derek; Chun, Seung; Sun, Shuying; Ling, Shuo-Chien; Myers, Brian; Engelhardt, Jeffery; Katz, Melanie; Baughn, Michael; Platoshyn, Oleksandr; Marsala, Martin; Watt, Andy; Heyser, Charles J; Ard, M Colin; De Muynck, Louis; Daughrity, Lillian M; Swing, Deborah A; Tessarollo, Lino; Jung, Chris J; Delpoux, Arnaud; Utzschneider, Daniel T; Hedrick, Stephen M; de Jong, Pieter J; Edbauer, Dieter; Van Damme, Philip; Petrucelli, Leonard; Shaw, Christopher E; Bennett, C Frank; Da Cruz, Sandrine; Ravits, John; Rigo, Frank; Cleveland, Don W; Lagier-Tourenne, Clotilde

    2016-05-04

    Hexanucleotide expansions in C9ORF72 are the most frequent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Disease mechanisms were evaluated in mice expressing C9ORF72 RNAs with up to 450 GGGGCC repeats or with one or both C9orf72 alleles inactivated. Chronic 50% reduction of C9ORF72 did not provoke disease, while its absence produced splenomegaly, enlarged lymph nodes, and mild social interaction deficits, but not motor dysfunction. Hexanucleotide expansions caused age-, repeat-length-, and expression-level-dependent accumulation of RNA foci and dipeptide-repeat proteins synthesized by AUG-independent translation, accompanied by loss of hippocampal neurons, increased anxiety, and impaired cognitive function. Single-dose injection of antisense oligonucleotides (ASOs) that target repeat-containing RNAs but preserve levels of mRNAs encoding C9ORF72 produced sustained reductions in RNA foci and dipeptide-repeat proteins, and ameliorated behavioral deficits. These efforts identify gain of toxicity as a central disease mechanism caused by repeat-expanded C9ORF72 and establish the feasibility of ASO-mediated therapy.

  7. Distinct C9orf72-Associated Dipeptide Repeat Structures Correlate with Neuronal Toxicity

    Science.gov (United States)

    Krans, Amy; Sawaya, Michael R.; Paulson, Henry L.; Todd, Peter K.; Barmada, Sami J.; Ivanova, Magdalena I.

    2016-01-01

    Hexanucleotide repeat expansions in C9orf72 are the most common inherited cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The expansions elicit toxicity in part through repeat-associated non-AUG (RAN) translation of the intronic (GGGGCC)n sequence into dipeptide repeat-containing proteins (DPRs). Little is known, however, about the structural characteristics and aggregation propensities of the dipeptide units comprising DPRs. To address this question, we synthesized dipeptide units corresponding to the three sense-strand RAN translation products, analyzed their structures by circular dichroism, electron microscopy and dye binding assays, and assessed their relative toxicity when applied to primary cortical neurons. Short, glycine-arginine (GR)3 dipeptides formed spherical aggregates and selectively reduced neuronal survival compared to glycine-alanine (GA)3 and glycine-proline (GP)3 dipeptides. Doubling peptide length had little effect on the structure of GR or GP peptides, but (GA)6 peptides formed β-sheet rich aggregates that bound thioflavin T and Congo red yet lacked the typical fibrillar morphology of amyloids. Aging of (GA)6 dipeptides increased their β-sheet content and enhanced their toxicity when applied to neurons. We also observed that the relative toxicity of each tested dipeptide was proportional to peptide internalization. Our results demonstrate that different C9orf72-related dipeptides exhibit distinct structural properties that correlate with their relative toxicity. PMID:27776165

  8. Ground Wood Fiber Length Distributions

    Directory of Open Access Journals (Sweden)

    Lauri Ilmari Salminen

    2014-01-01

    Full Text Available This study considers ground wood fiber length distributions arising from pilot grindings. The empirical fiber length distributions appear to be independent of wood fiber length as well as feeding velocity. In terms of mathematics the fiber fragment distributions of ground wood pulp combine an exponential distribution for high-length fragments and a power-law distribution for smaller lengths. This implies that the fiber length distribution is influenced by the stone surface. A fragmentation-based model is presented that allows reproduction of the empirical results.

  9. Study on correlation between the fetal lumbar spine length and gestational age and sexual dimorphisms by 3 .0T MR%胎儿腰椎长度发育与孕龄及性别相关性3.0T 磁共振研究

    Institute of Scientific and Technical Information of China (English)

    赵慧; 王光彬; 林祥涛; 徐艳霞; 肖连祥; 吴勇; 董金叶; 汤煜春; 张忠和; 刘树伟

    2015-01-01

    Objective Using the magnetic resonance imaging (MRI) to research the normal fetal lumbar spine length at varying gestational ages and sex dimorphisms ,we investigated a more sensitive nomogram of fetal spine length and gesta‐tional ages .Methods This research was a prospective study .Postmortem MR imaging was performed on 71 fetuses ,ran‐ging between 16 ~ 42 gestational ages .3D‐T2 WI of the whole spine was performed in sagittal planed ,and then recon‐structd in the coronal ,sagittal and axial planed based the L2 vertebra ,to measure the length of the lumbar spine in the midcogtal planed .Liner regression equation was established .And the developmental changes with sexual dimorphisms were analyzed .Results A statistically significant increase in all measurements was found with advancing gestational age . The length of lumbar spine increased linearly from (1 .96 ± 0 .13) to (5 .54 ± 0 .42) cm for the 16‐week and 42‐week groups of gestation ,respectively ,the function was represented by the regression .The lumbar segment length was ‐0 .401 + 0 .147 × gestational age ,R2 = 0 .98 ,Sexual dimorphisms was not detected .Conclusion The fetal spine length appears as an eas‐ily acquired and valuable parameter ,which strongly correlates with gestational age .No significant differences were ob‐served in the values for the parament studued according to sex .Therefor ,lumbar spine length is the best predictor of ges‐tational age among the parameters .It is useful in assessing morphologic maturity of fetuses .%目的:利用3.0T磁共振研究正常胎儿标本腰椎长度随孕周增加的变化规律及不同性别间差异,绘制腰段脊柱生长曲线。方法利用3.0T MR 扫描仪对71例16~42周自然流产及因母体或胎儿因素引产的胎儿新鲜标本行全脊柱3D‐T2 WI 序列扫描,对所得图像以 L2椎体为中心进行三方位重建,在正中矢状位上测量腰椎长度,对测量参数和孕周作回归分析,

  10. Maternal telomere length inheritance in the king penguin.

    Science.gov (United States)

    Reichert, S; Rojas, E R; Zahn, S; Robin, J-P; Criscuolo, F; Massemin, S

    2015-01-01

    Telomeres are emerging as a biomarker for ageing and survival, and are likely important in shaping life-history trade-offs. In particular, telomere length with which one starts in life has been linked to lifelong survival, suggesting that early telomere dynamics are somehow related to life-history trajectories. This result highlights the importance of determining the extent to which telomere length is inherited, as a crucial factor determining early life telomere length. Given the scarcity of species for which telomere length inheritance has been studied, it is pressing to assess the generality of telomere length inheritance patterns. Further, information on how this pattern changes over the course of growth in individuals living under natural conditions should provide some insight on the extent to which environmental constraints also shape telomere dynamics. To fill this gap partly, we followed telomere inheritance in a population of king penguins (Aptenodytes patagonicus). We tested for paternal and maternal influence on chick initial telomere length (10 days old after hatching), and how these relationships changed with chick age (at 70, 200 and 300 days old). Based on a correlative approach, offspring telomere length was positively associated with maternal telomere length early in life (at 10 days old). However, this relationship was not significant at older ages. These data suggest that telomere length in birds is maternally inherited. Nonetheless, the influence of environmental conditions during growth remained an important factor shaping telomere length, as the maternal link disappeared with chicks' age.

  11. Nonpharmacological Interventions Targeted at Delirium Risk Factors, Delivered by Trained Volunteers (Medical and Psychology Students), Reduced Need for Antipsychotic Medications and the Length of Hospital Stay in Aged Patients Admitted to an Acute Internal Medicine Ward: Pilot Study.

    Science.gov (United States)

    Gorski, Stanislaw; Piotrowicz, Karolina; Rewiuk, Krzysztof; Halicka, Monika; Kalwak, Weronika; Rybak, Paulina; Grodzicki, Tomasz

    2017-01-01

    Purpose. Effectiveness of nonpharmacological multicomponent prevention delivered by trained volunteers (medical and psychology students), targeted at delirium risk factors in geriatric inpatients, was assessed at an internal medicine ward in Poland. Patients and Methods. Participants were recruited to intervention and control groups at the internal medicine ward (inclusion criteria: age ≥ 75, acute medical condition, basic orientation, and logical contact on admission; exclusion criteria: life expectancy internal medicine ward.

  12. Analysis of repeated measures data

    CERN Document Server

    Islam, M Ataharul

    2017-01-01

    This book presents a broad range of statistical techniques to address emerging needs in the field of repeated measures. It also provides a comprehensive overview of extensions of generalized linear models for the bivariate exponential family of distributions, which represent a new development in analysing repeated measures data. The demand for statistical models for correlated outcomes has grown rapidly recently, mainly due to presence of two types of underlying associations: associations between outcomes, and associations between explanatory variables and outcomes. The book systematically addresses key problems arising in the modelling of repeated measures data, bearing in mind those factors that play a major role in estimating the underlying relationships between covariates and outcome variables for correlated outcome data. In addition, it presents new approaches to addressing current challenges in the field of repeated measures and models based on conditional and joint probabilities. Markov models of first...

  13. Instability of human TATA-binding protein CAG triplet repeats during amplification by PCR.

    Science.gov (United States)

    Holstege, F C; van der Vliet, P C; Timmers, H T

    1994-09-13

    Polymerase chain reaction (PCR) of a TATA-binding protein cDNA that contains CAG triplet repeats results in heterogeneous products. This is caused by a variable loss in the number of CAG triplets. Sequence analysis of PCR products suggests that instability increases with repeat length.

  14. HA novel approach to investigate tissue-specific trinucleotide repeat instability

    Directory of Open Access Journals (Sweden)

    Boily Marie-Josee

    2010-03-01

    Full Text Available Abstract Background In Huntington's disease (HD, an expanded CAG repeat produces characteristic striatal neurodegeneration. Interestingly, the HD CAG repeat, whose length determines age at onset, undergoes tissue-specific somatic instability, predominant in the striatum, suggesting that tissue-specific CAG length changes could modify the disease process. Therefore, understanding the mechanisms underlying the tissue specificity of somatic instability may provide novel routes to therapies. However progress in this area has been hampered by the lack of sensitive high-throughput instability quantification methods and global approaches to identify the underlying factors. Results Here we describe a novel approach to gain insight into the factors responsible for the tissue specificity of somatic instability. Using accurate genetic knock-in mouse models of HD, we developed a reliable, high-throughput method to quantify tissue HD CAG repeat instability and integrated this with genome-wide bioinformatic approaches. Using tissue instability quantified in 16 tissues as a phenotype and tissue microarray gene expression as a predictor, we built a mathematical model and identified a gene expression signature that accurately predicted tissue instability. Using the predictive ability of this signature we found that somatic instability was not a consequence of pathogenesis. In support of this, genetic crosses with models of accelerated neuropathology failed to induce somatic instability. In addition, we searched for genes and pathways that correlated with tissue instability. We found that expression levels of DNA repair genes did not explain the tissue specificity of somatic instability. Instead, our data implicate other pathways, particularly cell cycle, metabolism and neurotransmitter pathways, acting in combination to generate tissue-specific patterns of instability. Conclusion Our study clearly demonstrates that multiple tissue factors reflect the level of

  15. Reduction and technical simplification of testing protocol for walking based on repeatability analyses: An Interreg IVa pilot study

    Directory of Open Access Journals (Sweden)

    Nejc Sarabon

    2010-12-01

    Full Text Available The aim of this study was to define the most appropriate gait measurement protocols to be used in our future studies in the Mobility in Ageing project. A group of young healthy volunteers took part in the study. Each subject carried out a 10-metre walking test at five different speeds (preferred, very slow, very fast, slow, and fast. Each walking speed was repeated three times, making a total of 15 trials which were carried out in a random order. Each trial was simultaneously analysed by three observers using three different technical approaches: a stop watch, photo cells and electronic kinematic dress. In analysing the repeatability of the trials, the results showed that of the five self-selected walking speeds, three of them (preferred, very fast, and very slow had a significantly higher repeatability of the average walking velocity, step length and cadence than the other two speeds. Additionally, the data showed that one of the three technical methods for gait assessment has better metric characteristics than the other two. In conclusion, based on repeatability, technical and organizational simplification, this study helped us to successfully define a simple and reliable walking test to be used in the main study of the project.

  16. Mechanisms of trinucleotide repeat instability during human development.

    Science.gov (United States)

    McMurray, Cynthia T

    2010-11-01

    Trinucleotide expansion underlies several human diseases. Expansion occurs during multiple stages of human development in different cell types, and is sensitive to the gender of the parent who transmits the repeats. Repair and replication models for expansions have been described, but we do not know whether the pathway involved is the same under all conditions and for all repeat tract lengths, which differ among diseases. Currently, researchers rely on bacteria, yeast and mice to study expansion, but these models differ substantially from humans. We need now to connect the dots among human genetics, pathway biochemistry and the appropriate model systems to understand the mechanism of expansion as it occurs in human disease.

  17. New primer for specific amplification of the CAG repeat in Huntington disease alleles

    Energy Technology Data Exchange (ETDEWEB)

    Bond, C.E.; Hodes, M.E. [Indiana Univ. School of Medicine, Indianapolis (United States)

    1994-09-01

    Huntington disease is an autosomal dominant neurodegenerative disorder caused by an expansion of a CAG trinucleotide repeat near the 5{prime} end of the gene for Huntington disease (IT15). The CAG repeat is flanked by a variable-length CCG repeat that is included in the amplification product obtained with most currently used primer sets and PCR protocols. Inclusion of this adjacent CCG repeat complicates the accurate assessment of CAG repeat length and interferes with the genotype determination of those individuals carrying alleles in the intermediate range between normal and expanded sized. Due to the GC-rich nature of this region, attempts at designing a protocol for amplification of only the CAG repeat have proved unreliable and difficult to execute. We report here the development of a compatible primer set and PCR protocol that yields consistent amplification of the CAG-repeat region. PCR products can be visualized in ethidium bromide-stained agarose gels for rapid screening or in 6% polyacrylamide gels for determination of exact repeat length. This assay produces bands that can be sized accurately, while eliminating most nonspecific products. Fifty-five specimens examined showed consistency with another well-known method, but one that amplifies the CCG repeats as well. The results we obtained also matched the known carrier status of the donors.

  18. Environmental stresses disrupt telomere length homeostasis.

    Directory of Open Access Journals (Sweden)

    Gal Hagit Romano

    Full Text Available Telomeres protect the chromosome ends from degradation and play crucial roles in cellular aging and disease. Recent studies have additionally found a correlation between psychological stress, telomere length, and health outcome in humans. However, studies have not yet explored the causal relationship between stress and telomere length, or the molecular mechanisms underlying that relationship. Using yeast as a model organism, we show that stresses may have very different outcomes: alcohol and acetic acid elongate telomeres, whereas caffeine and high temperatures shorten telomeres. Additional treatments, such as oxidative stress, show no effect. By combining genome-wide expression measurements with a systematic genetic screen, we identify the Rap1/Rif1 pathway as the central mediator of the telomeric response to environmental signals. These results demonstrate that telomere length can be manipulated, and that a carefully regulated homeostasis may become markedly deregulated in opposing directions in response to different environmental cues.

  19. Aging changes in sleep

    Science.gov (United States)

    Sleep normally occurs in several stages. The sleep cycle includes: Dreamless periods of light and deep sleep Some periods of active dreaming (REM sleep) The sleep cycle is repeated several times during the night. AGING ...

  20. Leg Length Versus Torso Length in Pedophilia: Further Evidence of Atypical Physical Development Early in Life.

    Science.gov (United States)

    Fazio, Rachel L; Dyshniku, Fiona; Lykins, Amy D; Cantor, James M

    2015-10-12

    Adult men's height results from an interaction among positive and negative influences, including genetic predisposition, conditions in utero, and influences during early development such as nutritional quality, pathogen exposure, and socioeconomic status. Decreased height, reflected specifically as a decreased leg length, is strongly associated with increased risk of poorer health outcomes. Although prior research has repeatedly shown that pedophiles are shorter than nonpedophiles, the largest study to date relied on self-reported height. In the present study, pedophiles demonstrated reduced measured height and reduced leg length as compared with teleiophiles. Given the prenatal and early childhood origins of height, these findings contribute additional evidence to a biological, developmental origin of pedophilia. In addition, the magnitude of this height difference was substantially larger than that found in children exposed to a variety of early environmental stressors, but similar to that seen in other biologically based neurodevelopmental disorders.

  1. Repeatability of Response to Asthma Medications

    Science.gov (United States)

    Wu, Ann; Tantisira, Kelan; Li, Lingling; Schuemann, Brooke; Weiss, Scott

    2010-01-01

    Background Pharmacogenetic studies of drug response in asthma assume that patients respond consistently to a treatment but that treatment response varies across patients, however, no formal studies have demonstrated this. Objective To determine the repeatability of commonly used outcomes for treatment response to asthma medications: bronchodilator response, forced expiratory volume in 1 second (FEV1), and provocative concentration of methacholine producing a 20% decline in FEV1 (PC20). Methods The Childhood Asthma Management Program (CAMP) was a multi-center clinical trial of children randomized to receiving budesonide, nedocromil, or placebo. We determined the intraclass correlation coefficient (ICC) for each outcome over repeated visits over four years in CAMP using mixed effects regression models. We adjusted for the covariates: age, race/ethnicity, height, family income, parental education, and symptom score. We incorporated each outcome for each child as repeated outcome measurements and stratified by treatment group. Results The ICC for bronchodilator response was 0.31 in the budesonide group, 0.35 in the nedocromil group, and 0.40 in the placebo group, after adjusting for covariates. The ICC for FEV1 was 0.71 in the budesonide group, 0.60 in the nedocromil group, and 0.69 in the placebo group, after adjusting for covariates. The ICC for PC20 was 0.67 in the budesonide and placebo groups and 0.73 in the nedocromil group, after adjusting for covariates. Conclusion The within treatment group repeatability of FEV1 and PC20 are high; thus these phenotypes are heritable. FEV1 and PC20 may be better phenotypes than bronchodilator response for studies of treatment response in asthma. PMID:19064281

  2. Shorter CAG repeat in the AR gene is associated with atypical hyperplasia and breast carcinoma

    DEFF Research Database (Denmark)

    De Abreu, Francine Blumental; Pirolo, Leandro Júnior; Canevari, Renata de Azevedo

    2007-01-01

    -based GeneScan analysis was used to investigate the [CAG]n repeat length at exon 1 of the AR gene in 59 benign breast lesions (27 fibroadenomas, 18 atypical hyperplasias, and 14 hyperplasias without atypia) and 54 ductal breast carcinomas. Seventy-two cancer-free women were used as a control group....... In addition, [CAG]n repeats were evaluated for the presence of loss of heterozygosity (LOH) and microsatellite instability (MSI) in a subset of these samples (27 fibroadenomas, 14 hyperplasias without atypia and 22 breast carcinomas). RESULTS: Shorter [CAG]n repeat lengths were strongly correlated...

  3. Verification of somatic CAG repeat expansion by pre-PCR fractionation.

    Science.gov (United States)

    Hunter, Jesse M; Crouse, Andrew B; Lesort, Mathieu; Johnson, Gail V W; Detloff, Peter J

    2005-05-15

    The inheritance of a long CAG repeat causes several late onset neurological disorders including Huntington's disease (HD). Longer CAG repeats correlate with earlier onset of HD suggesting an increased toxicity for the products of long repeat alleles. PCR based data has been used to show that HD CAG repeat expansion beyond the inherited length occurs in affected tissues indicating a possible role for somatic instability in the disease process. PCR, however, is prone to artifacts resulting from expansion of repeat sequences during amplification. We describe a method to distinguish between CAG repeat expansions that exist in vivo and those that potentially occur during PCR. The method involves size fractionation of genomic restriction fragments containing the expanded repeats followed by PCR amplification. The application of this method confirms the presence of somatic expansions in the brains of a knock-in mouse model of HD.

  4. Leukocyte Telomere Length and Late-Life Depression

    NARCIS (Netherlands)

    Schaakxs, Roxanne; Verhoeven, Josine E.; Oude Voshaar, Richard; Comijs, Hannie C.; Penninx, Brenda W. J. H.

    2015-01-01

    OBJECTIVE: Depressive disorders have been associated with increased risk for aging-related diseases, possibly as a consequence of accelerated cellular aging. Cellular aging, indexed by telomere length (TL) shortening, has been linked to depression in adults younger than 60 years; however, it remains

  5. Leukocyte telomere length and late-life depression

    NARCIS (Netherlands)

    Schaakxs, R.; Verhoeven, J.E.; Oude Voshaar, R.C.; Comijs, H.C.; Penninx, B.W.

    2015-01-01

    OBJECTIVE: Depressive disorders have been associated with increased risk for aging-related diseases, possibly as a consequence of accelerated cellular aging. Cellular aging, indexed by telomere length (TL) shortening, has been linked to depression in adults younger than 60 years; however, it remains

  6. Limitations on quantum key repeaters.

    Science.gov (United States)

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-23

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  7. CAG-encoded polyglutamine length polymorphism in the human genome

    Directory of Open Access Journals (Sweden)

    Hayden Michael R

    2007-05-01

    Full Text Available Abstract Background Expansion of polyglutamine-encoding CAG trinucleotide repeats has been identified as the pathogenic mutation in nine different genes associated with neurodegenerative disorders. The majority of individuals clinically diagnosed with spinocerebellar ataxia do not have mutations within known disease genes, and it is likely that additional ataxias or Huntington disease-like disorders will be found to be caused by this common mutational mechanism. We set out to determine the length distributions of CAG-polyglutamine tracts for the entire human genome in a set of healthy individuals in order to characterize the nature of polyglutamine repeat length variation across the human genome, to establish the background against which pathogenic repeat expansions can be detected, and to prioritize candidate genes for repeat expansion disorders. Results We found that repeats, including those in known disease genes, have unique distributions of glutamine tract lengths, as measured by fragment analysis of PCR-amplified repeat regions. This emphasizes the need to characterize each distribution and avoid making generalizations between loci. The best predictors of known disease genes were occurrence of a long CAG-tract uninterrupted by CAA codons in their reference genome sequence, and high glutamine tract length variance in the normal population. We used these parameters to identify eight priority candidate genes for polyglutamine expansion disorders. Twelve CAG-polyglutamine repeats were invariant and these can likely be excluded as candidates. We outline some confusion in the literature about this type of data, difficulties in comparing such data between publications, and its application to studies of disease prevalence in different populations. Analysis of Gene Ontology-based functions of CAG-polyglutamine-containing genes provided a visual framework for interpretation of these genes' functions. All nine known disease genes were involved in DNA

  8. Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

    Energy Technology Data Exchange (ETDEWEB)

    Provenzano, Virgil [National Institute of Standards and Technology, Gaithersburg, MD 20899 (United States); Della Torre, Edward; Bennett, Lawrence H. [Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052 (United States); ElBidweihy, Hatem, E-mail: Hatem@gwmail.gwu.edu [Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052 (United States)

    2014-02-15

    The Gd{sub 5}Ge{sub 2}Si{sub 2} alloy and the off-stoichiometric Ni{sub 50}Mn{sub 35}In{sub 15} Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd{sub 5}Ge{sub 2}Si{sub 2} and Ni{sub 50}Mn{sub 35}In{sub 15} alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis.

  9. IMPEDANCE OF FINITE LENGTH RESISTOR

    Energy Technology Data Exchange (ETDEWEB)

    KRINSKY, S.; PODOBEDOV, B.; GLUCKSTERN, R.L.

    2005-05-15

    We determine the impedance of a cylindrical metal tube (resistor) of radius a, length g, and conductivity {sigma}, attached at each end to perfect conductors of semi-infinite length. Our main interest is in the asymptotic behavior of the impedance at high frequency, k >> 1/a. In the equilibrium regime, , the impedance per unit length is accurately described by the well-known result for an infinite length tube with conductivity {sigma}. In the transient regime, ka{sup 2} >> g, we derive analytic expressions for the impedance and wakefield.

  10. Polyketide chain length control by chain length factor.

    Science.gov (United States)

    Tang, Yi; Tsai, Shiou-Chuan; Khosla, Chaitan

    2003-10-22

    Bacterial aromatic polyketides are pharmacologically important natural products. A critical parameter that dictates product structure is the carbon chain length of the polyketide backbone. Systematic manipulation of polyketide chain length represents a major unmet challenge in natural product biosynthesis. Polyketide chain elongation is catalyzed by a heterodimeric ketosynthase. In contrast to homodimeric ketosynthases found in fatty acid synthases, the active site cysteine is absent from the one subunit of this heterodimer. The precise role of this catalytically silent subunit has been debated over the past decade. We demonstrate here that this subunit is the primary determinant of polyketide chain length, thereby validating its designation as chain length factor. Using structure-based mutagenesis, we identified key residues in the chain length factor that could be manipulated to convert an octaketide synthase into a decaketide synthase and vice versa. These results should lead to novel strategies for the engineered biosynthesis of hitherto unidentified polyketide scaffolds.

  11. Curve Length Estimation using Vertix Chain Code Curve Length Estimation

    Directory of Open Access Journals (Sweden)

    Habibollah Haron

    2010-09-01

    Full Text Available Most of the applications in image analysis are based on Freeman chain code. In this paper, for the first time, vertex chain code (VCC proposed by Bribiesca is applied to improve length estimation of the 2D digitized curve. The chain code has some preferences such as stable in shifting, turning, mirroring movement of image and has normalized starting point. Due to the variety of length estimator methods, we focused on the three specific techniques. First, the way Bribiesca proposed which is based on counting links between vertices;