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Find video protocols related to scientific articles indexed in Pubmed.
Digital genotyping of macrosatellites and multicopy genes reveals novel biological functions associated with copy number variation of large tandem repeats.
PLoS Genet.
PUBLISHED: 06-01-2014
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Tandem repeats are common in eukaryotic genomes, but due to difficulties in assaying them remain poorly studied. Here, we demonstrate the utility of Nanostring technology as a targeted approach to perform accurate measurement of tandem repeats even at extremely high copy number, and apply this technology to genotype 165 HapMap samples from three different populations and five species of non-human primates. We observed extreme variability in copy number of tandemly repeated genes, with many loci showing 5-10 fold variation in copy number among humans. Many of these loci show hallmarks of genome assembly errors, and the true copy number of many large tandem repeats is significantly under-represented even in the high quality 'finished' human reference assembly. Importantly, we demonstrate that most large tandem repeat variations are not tagged by nearby SNPs, and are therefore essentially invisible to SNP-based GWAS approaches. Using association analysis we identify many cis correlations of large tandem repeat variants with nearby gene expression and DNA methylation levels, indicating that variations of tandem repeat length are associated with functional effects on the local genomic environment. This includes an example where expansion of a macrosatellite repeat is associated with increased DNA methylation and suppression of nearby gene expression, suggesting a mechanism termed "repeat induced gene silencing", which has previously been observed only in transgenic organisms. We also observed multiple signatures consistent with altered selective pressures at tandemly repeated loci, suggesting important biological functions. Our studies show that tandemly repeated loci represent a highly variable fraction of the genome that have been systematically ignored by most previous studies, copy number variation of which can exert functionally significant effects. We suggest that future studies of tandem repeat loci will lead to many novel insights into their role in modulating both genomic and phenotypic diversity.
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Histone H3.3 and its proteolytically processed form drive a cellular senescence programme.
Nat Commun
PUBLISHED: 03-21-2014
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The process of cellular senescence generates a repressive chromatin environment, however, the role of histone variants and histone proteolytic cleavage in senescence remains unclear. Here, using models of oncogene-induced and replicative senescence, we report novel histone H3 tail cleavage events mediated by the protease Cathepsin L. We find that cleaved forms of H3 are nucleosomal and the histone variant H3.3 is the preferred cleaved form of H3. Ectopic expression of H3.3 and its cleavage product (H3.3cs1), which lacks the first 21 amino acids of the H3 tail, is sufficient to induce senescence. Further, H3.3cs1 chromatin incorporation is mediated by the HUCA histone chaperone complex. Genome-wide transcriptional profiling revealed that H3.3cs1 facilitates transcriptional silencing of cell cycle regulators including RB/E2F target genes, likely via the permanent removal of H3K4me3. Collectively, our study identifies histone H3.3 and its proteolytically processed forms as key regulators of cellular senescence.
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Histone variants: emerging players in cancer biology.
Cell. Mol. Life Sci.
PUBLISHED: 04-11-2013
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Histone variants are key players in shaping chromatin structure, and, thus, in regulating fundamental cellular processes such as chromosome segregation and gene expression. Emerging evidence points towards a role for histone variants in contributing to tumor progression, and, recently, the first cancer-associated mutation in a histone variant-encoding gene was reported. In addition, genetic alterations of the histone chaperones that specifically regulate chromatin incorporation of histone variants are rapidly being uncovered in numerous cancers. Collectively, these findings implicate histone variants as potential drivers of cancer initiation and/or progression, and, therefore, targeting histone deposition or the chromatin remodeling machinery may be of therapeutic value. Here, we review the mammalian histone variants of the H2A and H3 families in their respective cellular functions, and their involvement in tumor biology.
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MacroH2A histone variants act as a barrier upon reprogramming towards pluripotency.
Nat Commun
PUBLISHED: 02-07-2013
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The chromatin template imposes an epigenetic barrier during the process of somatic cell reprogramming. Using fibroblasts derived from macroH2A double knockout (dKO) mice, here we show that these histone variants act cooperatively as a barrier to induced pluripotency. Through manipulation of macroH2A isoforms, we further demonstrate that macroH2A2 is the predominant barrier to reprogramming. Genomic analyses reveal that macroH2A1 and macroH2A2, together with H3K27me3, co-occupy pluripotency genes in wild-type (wt) fibroblasts. In particular, we find macroH2A isoforms to be highly enriched at target genes of the K27me3 demethylase, Utx, which are reactivated early in iPS reprogramming. Finally, while macroH2A dKO-induced pluripotent cells are able to differentiate properly in vitro and in vivo, such differentiated cells retain the ability to return to a stem-like state. Therefore, we propose that macroH2A isoforms provide a redundant silencing layer or terminal differentiation lock at critical pluripotency genes that presents as an epigenetic barrier when differentiated cells are challenged to reprogram.
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The octamer is the major form of CENP-A nucleosomes at human centromeres.
Nat. Struct. Mol. Biol.
PUBLISHED: 01-25-2013
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The centromere is the chromosomal locus that ensures fidelity in genome transmission at cell division. Centromere protein A (CENP-A) is a histone H3 variant that specifies centromere location independently of DNA sequence. Conflicting evidence has emerged regarding the histone composition and stoichiometry of CENP-A nucleosomes. Here we show that the predominant form of the CENP-A particle at human centromeres is an octameric nucleosome. CENP-A nucleosomes are very highly phased on ?-satellite 171-base-pair monomers at normal centromeres and also display strong positioning at neocentromeres. At either type of functional centromere, CENP-A nucleosomes exhibit similar DNA-wrapping behavior, as do octameric CENP-A nucleosomes reconstituted with recombinant components, having looser DNA termini than those on conventional nucleosomes containing canonical histone H3. Thus, the fundamental unit of the chromatin that epigenetically specifies centromere location in mammals is an octameric nucleosome with loose termini.
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Acute stress induces hyperacusis in women with high levels of emotional exhaustion.
PLoS ONE
PUBLISHED: 01-02-2013
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Hearing problems is one of the top ten public health disorders in the general population and there is a well-established relationship between stress and hearing problems. The aim of the present study was to explore if an acute stress will increase auditory sensitivity (hyperacusis) in individuals with high levels of emotional exhaustion (EE).
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Role stress among first-line nurse managers and registered nurses - a comparative study.
J Nurs Manag
PUBLISHED: 10-21-2011
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Studies show that first-line nurse managers (F-LNMs) experience high psychological job demands and inadequate managerial guidance. The purpose of this study was to investigate whether F-LNMs have higher stress levels and show more signs of stress-related ill health than registered nurses (RNs).
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Formation of novel CENP-A domains on tandem repetitive DNA and across chromosome breakpoints on human chromosome 8q21 neocentromeres.
Chromosoma
PUBLISHED: 04-04-2011
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Endogenous human centromeres form on megabase-sized arrays of tandemly repeated alpha satellite DNA. Human neocentromeres form epigenetically at ectopic sites devoid of alpha satellite DNA and permit analysis of centromeric DNA and chromatin organization. In this study, we present molecular cytogenetic and CENP-A chromatin immunoprecipitation (ChIP) on CHIP analyses of two neocentromeres that have formed in chromosome band 8q21 each with a unique DNA and CENP-A chromatin configuration. The first neocentromere was found on a neodicentric chromosome 8 with an inactivated endogenous centromere, where the centromeric activity and CENP-A domain were repositioned to band 8q21 on a large tandemly repeated DNA. This is the first example of a neocentromere forming on repetitive DNA, as all other mapped neocentromeres have formed on single copy DNA. Quantitative fluorescent in situ hybridization (FISH) analysis showed a 60% reduction in the alpha satellite array size at the inactive centromere compared to the active centromere on the normal chromosome 8. This neodicentric chromosome may provide insight into centromere inactivation and the role of tandem DNA in centromere structure. The second neocentromere was found on a neocentric ring chromosome that contained the 8q21 tandemly repeated DNA, although the neocentromere was localized to a different genomic region. Interestingly, this neocentromere is composed of two distinct CENP-A domains in bands 8q21 and 8q24, which are brought into closer proximity on the ring chromosome. This neocentromere suggests that chromosomal rearrangement and DNA breakage may be involved in neocentromere formation. These novel examples provide insight into the formation and structure of human neocentromeres.
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Stress and prevalence of hearing problems in the Swedish working population.
BMC Public Health
PUBLISHED: 02-23-2011
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Current human and experimental studies are indicating an association between stress and hearing problems; however potential risk factors have not been established. Hearing problems are projected to become among the top ten disabilities according to the WHO in the near future. Therefore a better understanding of the relationships between stress and hearing is warranted. Here we describe the prevalence of two common hearing problems, i.e. hearing complaints and tinnitus, in relation to different work-and health-related stressors.
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Possibilities and limitations of the Polar RS800 in measuring heart rate variability at rest.
Eur. J. Appl. Physiol.
PUBLISHED: 01-04-2011
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A growing trend among clinical studies is the use of heart rate monitors (HRMs) for assessment of heart rate variability (HRV). These instruments offer a convenient alternative to traditional electrocardiographs (ECGs) for recording and processing of R-R data. Reports on the validity of such systems are, however, conflicting. This study aimed to assess the validity of a commercial HRM on a large study sample, with emphasis on gender and age. Simultaneous recordings of R-R intervals were conducted with the Polar RS800 HRM and a 3-lead ECG on 341 individuals. Data editing was performed with individually designated software for each instrument. Agreement on SDNN, RMSSD, and HF- and LF power was assessed with intraclass correlations (ICCs), standard errors of measurement (SEMs) and Bland and Altman plots. The HRM was not able to identify 18 observations with non-sinus beats. For men, agreement between instruments ranged from good to excellent (ICC ? 0.8) on all HRV measures, and SEMs were generally small. For women the results were weaker, with unacceptable agreement between instruments on SDNN. Women over 60 years did not reach a critical ICC value of 0.75 on any of the HRV measures. Bland and Altman plots demonstrated that the RS800 generally overestimated HRV, and that uncertainty increased with higher values. Since the Polar system did not identify errors satisfactorily, or return valid values of HRV for certain groups, it is concluded that, whenever possible, traditional ECGs should be used for both gathering and editing of HRV data.
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Declining sleep quality among nurses: a population-based four-year longitudinal study on the transition from nursing education to working life.
PLoS ONE
PUBLISHED: 06-09-2010
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Several studies have established impaired sleep is a common problem among nurses. Overworked, fatigued and stressed nurses are at a higher risk of making mistakes that threaten patient safety as well as their own health. The aim of the present study was to longitudinally monitor the development of sleep quality in nurses, starting from the last semester at the university, with three subsequent annual follow-ups once the nurses had entered working life.
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A paucity of heterochromatin at functional human neocentromeres.
Epigenetics Chromatin
PUBLISHED: 03-08-2010
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Centromeres are responsible for the proper segregation of replicated chromatids during cell division. Neocentromeres are fully functional ectopic human centromeres that form on low-copy DNA sequences and permit analysis of centromere structure in relation to the underlying DNA sequence. Such structural analysis is not possible at endogenous centromeres because of the large amounts of repetitive alpha satellite DNA present.
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Trends in self-rated health among nurses: a 4-year longitudinal study on the transition from nursing education to working life.
J Prof Nurs
PUBLISHED: 02-05-2010
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For nurses, the transition from higher education to working life involves several types of changes and seems to be a major contributing cause of distress and, consequently, ill health on a longer term basis. The aim of this study was to longitudinally monitor the development of self-rated health (SRH) in nurses, starting from the last semester at the university with subsequent follow-ups when the nurses had entered working life. The Longitudinal Analyses of Nurses Education and working life is an ongoing nationwide longitudinal project focusing on mapping health and career development in nurses in Sweden. SRH is one of the most widely used single-item measures of perceived health status with a well-established predictive ability on future health outcomes, including morbidity and mortality. This study found a small but significant and continuous decline in SRH among nurses during 3 years of follow-ups, starting from their last semester of nursing education and continuing 3 years into their working life. The most pronounced decline in SRH seems to occur in the transition between student life and working life and is most explicit among the youngest nurses. However, the long-term effect on SRH when entering into working life seems to be more pronounced among the older nurses.
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Internet-based assessment and self-monitoring of problematic alcohol and drug use.
Addict Behav
PUBLISHED: 01-04-2010
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A Swedish web-based service (www.escreen.se) offers self-assessment and self-monitoring of alcohol and drug use via on-line screening with the Alcohol Use Disorders Identification Test (AUDIT) and the Drug Use Disorders Identification Test (DUDIT) as well as in-depth risk assessment using extended versions of both tests (Alcohol-E and DUDIT-E). Users receive individualized feedback concerning their alcohol and drug consumption and can follow their alcohol and drug use over time in personal diagrams and by writing in an electronic diary. This study describes user characteristics, service utilization patterns, and psychometric test properties for 2361 individuals who created a valid account over 20 months starting in February 2007. Problematic alcohol use according to AUDIT criteria was indicated for 67.4%, while 46.0% met DUDIT criteria for problematic drug use. Men and women accessed the service equally, with a mean age of 23 years. Internal consistency reliability figures were 0.90 for 1846 first-time AUDIT users and 0.97 for 1211 first-time DUDIT users; among 213 second-time AUDIT users reliability was 0.93, and 0.96 for 97 second-time DUDIT users. Internet-based alcohol and drug monitoring could function as a self-help tool or as a complement to substance abuse treatment.
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Self-rated health and allostatic load in women working in two occupational sectors.
J Health Psychol
PUBLISHED: 04-23-2009
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This study set out to investigate how biological dysregulation, in terms of allostatic load (AL), relates to self-rated health (SRH) in women. Data on SRH and 12 biomarkers used to assess AL were available for 241 employees from the health care sector and 98 employees from the IT/media sector. In line with the hypothesis, results showed that a poor SRH, along with occupational sector, age and education, were significantly associated with a high AL, particularly for those working within the health care sector. This association between a poor SRH and AL, suggests a link between SRH and biological dysregulation.
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Psychosocial and physiological correlates of self-reported hearing problems in male and female musicians in symphony orchestras.
Int J Psychophysiol
PUBLISHED: 04-05-2009
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Experimental and epidemiological research indicate an association between long-term stress and hearing problems, yet the mechanisms underlying these disorders are not yet fully established. Thus, in order to better understand the pathogenesis of stress-related hearing problems, the present study explored the symptoms and general physiological and psychosocial status of musicians in symphony orchestras. Orchestral musicians are an ideal group to study since physical, psychosocial, work-environmental and acoustic stressors are highly prevalent. The subjects where obtained from two different studies. The first group included 250 participants from 12 orchestras and is entitled "the epidemiological study". The second group, entitled "the longitudinal study", included 47 musicians who were assessed at five occasions (every half year) during two years. Thirty-one of the 47 participants were selected for sampling of physiological variables, i.e. 24-hour ECG to assess heart rate variability to evaluate the synergistic action of the autonomic system as well as saliva cortisol and testosterone levels. The results indicate that self-reported hearing problems are associated with perceived poorer psychosocial environment, as well as mental health symptoms and stress. High-frequency power of heart rate variability (parasympathetic activity) showed a negative relationship to hearing problems, implying a poorer ability to "unwind" from stress. Cortisol levels were not correlated to hearing problems whereas testosterone levels showed a tendency to be lower in subjects with hearing problems than in others. These findings provide evidence for a relationship between long-term stress and self-reported hearing problems and demonstrate a protective role of parasympathetic and anabolic activity on hearing status.
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Associations between stress and hearing problems in humans.
Hear. Res.
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Hearing problems are a public health issue with prevalence figures far more common than previously estimated. There are well-established risk factors of hearing problems such as age, sex and noise exposure history. Here, we demonstrate additional risk factors, i.e. socioeconomic status and long-term stress exposure that are found to increase the risk of hearing problems. In order to proactively intervene and prevent hearing problems, these newly recognized risk factors need to be taken into consideration. When taking these new risk factors into account, sex differences become even more apparent than previously found. The aim of this review is to summarize our recent findings about the associations between stress and hearing problems.
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The correlation between the hyperacusis questionnaire and uncomfortable loudness levels is dependent on emotional exhaustion.
Int J Audiol
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To validate the hyperacusis questionnaire (HQ) in different strata of emotional exhaustion (EE).
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Tinnitus severity is reduced with reduction of depressive mood--a prospective population study in Sweden.
PLoS ONE
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Tinnitus, the perception of sound without external source, is a highly prevalent public health problem with about 8% of the population having frequently occurring tinnitus, and about 1-2% experiencing significant distress from it. Population studies, as well as studies on self-selected samples, have reported poor psychological well-being in individuals with tinnitus. However, no study has examined the long-term co-variation between mood and tinnitus prevalence or tinnitus severity. In this study, the relationship between depression and tinnitus prevalence and severity over a 2-year period was examined in a representative sample of the general Swedish working population. Results show that a decrease in depression is associated with a decrease in tinnitus prevalence, and even more markedly with tinnitus severity. Hearing loss was a more potent predictor than depression for tinnitus prevalence, but was a weaker predictor than depression for tinnitus severity. In addition, there were sex differences for tinnitus prevalence, but not for tinnitus severity. This study shows a direct and long-term association between tinnitus severity and depression.
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ATRX-mediated chromatin association of histone variant macroH2A1 regulates ?-globin expression.
Genes Dev.
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The histone variant macroH2A generally associates with transcriptionally inert chromatin; however, the factors that regulate its chromatin incorporation remain elusive. Here, we identify the SWI/SNF helicase ATRX (?-thalassemia/MR, X-linked) as a novel macroH2A-interacting protein. Unlike its role in assisting H3.3 chromatin deposition, ATRX acts as a negative regulator of macroH2As chromatin association. In human erythroleukemic cells deficient for ATRX, macroH2A accumulates at the HBA gene cluster on the subtelomere of chromosome 16, coinciding with the loss of ?-globin expression. Collectively, our results implicate deregulation of macroH2As distribution as a contributing factor to the ?-thalassemia phenotype of ATRX syndrome.
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Measuring risk online--feasibility of using FINDRISC in an online workplace survey.
Prim Care Diabetes
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With the globally increasing prevalence of diabetes and the knowledge on how to prevent the disease there is a high demand for an effective way of identifying people at risk. The hypothesis behind this investigation was that incorporation of the FINnish Diabetes Risk SCore (FINDRISC) questionnaire in a regular workplace survey would be a feasible way to identify individuals and groups at risk for diabetes that could benefit from preventive interventions.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.